SLN +ALN=Sentinel Lymph Node+Axillary Lymph Node

1 Summation of patients with mild and severe symptoms.

2 Odds ratio (SLN/ALN)

Table 1. A summary of incidence of lymphedema from the published studies.

Arm Lymphedema as a Consequence of Breast Cancer Therapy 39

Fig. 4. **A.** A relationship between local breast tangent radiation field and regional lymph nodes as depicted in the lateral beam's eye view with a tangential portal, where the superior border of the radiation portal is set below the heads of the clavicles (navy). **B.** The axial image through the dissected axilla demonstrates Level I (blue), Level II (purple), and Level III (dark green) axillary lymph nodal stations which are partially covered by the 90%

Does lymphedema have any risks associated with the use of systemic therapy? No significantly increased risk of incidence of lymphedema was observed in the literature with systemic therapy using hormonal treatment (Norman et al., 2010). Chemotherapy has been reported in some series to increase the complication rate associated with breast RT, including arm edema (Meek, 1998). However, no formal studies report any concrete data,

The main, "gold standard" of treatment for lymphedema is Combined, Complex or Comprehensive Decongestive Therapy (CDT) (Mayrovitz, 2009). The initial reductive phase of CDT treatment is known as Phase I. The main goals are to reduce the size of the affected location and to improve the skin. Phase II is known as the maintenance phase, where the patient self-manages to keep the effects of phase I treatment long term (Szuba, 2000; Hinrichs et al., 2004; Lasinski, 2002; Thomas et al., 2007; Koul et al., 2007). The effects of CDT include decreases in swelling, an increase in lymph drainage from the congested areas, a reduction in skin fibrosis and improvements in the skin conditions, an enhancement in the patient's functional status and quality of life as well as a relief in discomfort, and a reduced risk of cellulitis and Steward-Treves-Syndrome (a rare form of angiosarcoma) (Hammer et al., 2007; Mondry et al., 2004; Ferrandez, 1996; Franzcek et al., 1997; Hayes et al., 2008; Ahmed, 2008; Weiss, 2002; Kim et al.,

Components of Combined, Complex or Comprehensive Decongestive Therapy include manual lymph drainage (MLD), multi-layer, short-stretch compression bandaging, lymphatic exercise, skin care, and education in lymphedema management as well as elastic

2007; Cormier et al., 2009; Hormes et al., 2010; Fu et al., 2009; Vignes, 2006).

isodose area covering the breast tissue (orange).

which can predict such outcomes.

**4. Treatment of lymphedema** 

**4.1 Non-invasive management techniques** 

In the NSABP B-32 trial, at a 3-year follow-up lymphedema was assessed by both medical professionals and by patients themselves. When assessed by the former, the incidence of lymphedema was 303/1459 (20.8%) of patients in the SLND group in contrast with 431/1421 (30.3%) of cases of lymphedema in the ALND group. However, the patient selfassessment group demonstrated the rate of lymphedema as 10/320 (3.1%) in the SLND cohort and occurred in 25/307 (8.1%) of women in the ALND group (Ashikaga et al., 2008; Mansel et al., 2006). One of the largest retrospective reviews of a mature 10-year follow-up of experience from Thomas Jefferson University Hospital conducted by Wernicke et al, also assessed lymphedema by two methodologies. It was evident that regardless of whether the assessment was performed by a medical professional or a patient, there was statistically significant difference in the rates of this complication between the two cohorts as experienced by patients. When assessed by a medical professional, lymphedema was detectable in 6/111 (5.4%) of patients in the SLND group in contrast with 21/115 (18.3%) of cases of lymphedema in the ALND group, respectively (p<0.0001). The patient selfassessment groups demonstrated the lymphedema in 10/111 (10.0%) of patients in the SLND cohort and 39/115 (33.9%) of women reporting this complication in the ALND group (p<0.0001). This difference appears to be sustainable even a decade after the surgery, and the percentage of patients that experienced chronic lymphedema is significantly greater in the ALND cohort as compared with the SLND one (Wernicke et al., 2010) [Table 1].

The ACOSOG Z001 trial assessed patients with clinically positive axillary nodes (Aareleid et al. 2002). In this study, lymphedema was also assessed by the dual methodologies of a medical professional and a patient self-assessment. At a median follow-up age of 3 years, when assessed by a medical professional, lymphedema was detected in 14/226 (6%) of patients in the SLND group in contrast with 26/242 (11%) of cases of lymphedema in the ALND group. The patient self-assessment groups demonstrated the incidence of lymphedema in 14/253 (5%) of patients in the SLND cohort and 52/272 (19%) of women reporting this complication in the ALND group [Table I].

Could radiotherapy be a contributing factor to the complications of axillary surgery? If a low incidence of ALN failures lies in sterilization of the occult metastases in the axillary lymph nodes with the conventional breast tangential ports delivering RT to a patient in a supine position (Wernicke et al., 2010), radiotherapy may be at least in part responsible for the morbidity attributable to surgery. Goodman et al reported that with the standard radiation tangents, 90% of the Berg level I axilla and up to 70% of level II axillary lymph nodes received 95% of the prescribed dose to the breast (Smitt et al., 1999). Figure 4 demonstrates a typical patient treated with 3-D radiotherapy in the supine position with the standard tangential radiation fields targeting the breast tissue and inadvertently providing at least partial coverage for at least two of the Berg axillary levels. The vast majority of literature, with only a few negative studies, supports the fact that the modern 3-D tangential radiation port of the breast, administered in supine position, will at least partially irradiate the undissected axillary lymph nodes stations (Smitt et al., 1999; Takeda et al., 2000, 2004; Krasin et al., 2000; Aristei et al., 2001; Schlembach et al., 2001; **Orecchia et al., 2005;** Wong et al., 2008; Rabinovitch et al., 2008). This phenomenon may explain why even patients with SLND experience lymphedema as a long-term toxicity [Wernicke et al., 2010].

In the NSABP B-32 trial, at a 3-year follow-up lymphedema was assessed by both medical professionals and by patients themselves. When assessed by the former, the incidence of lymphedema was 303/1459 (20.8%) of patients in the SLND group in contrast with 431/1421 (30.3%) of cases of lymphedema in the ALND group. However, the patient selfassessment group demonstrated the rate of lymphedema as 10/320 (3.1%) in the SLND cohort and occurred in 25/307 (8.1%) of women in the ALND group (Ashikaga et al., 2008; Mansel et al., 2006). One of the largest retrospective reviews of a mature 10-year follow-up of experience from Thomas Jefferson University Hospital conducted by Wernicke et al, also assessed lymphedema by two methodologies. It was evident that regardless of whether the assessment was performed by a medical professional or a patient, there was statistically significant difference in the rates of this complication between the two cohorts as experienced by patients. When assessed by a medical professional, lymphedema was detectable in 6/111 (5.4%) of patients in the SLND group in contrast with 21/115 (18.3%) of cases of lymphedema in the ALND group, respectively (p<0.0001). The patient selfassessment groups demonstrated the lymphedema in 10/111 (10.0%) of patients in the SLND cohort and 39/115 (33.9%) of women reporting this complication in the ALND group (p<0.0001). This difference appears to be sustainable even a decade after the surgery, and the percentage of patients that experienced chronic lymphedema is significantly greater in the ALND cohort as compared with the SLND one (Wernicke et

The ACOSOG Z001 trial assessed patients with clinically positive axillary nodes (Aareleid et al. 2002). In this study, lymphedema was also assessed by the dual methodologies of a medical professional and a patient self-assessment. At a median follow-up age of 3 years, when assessed by a medical professional, lymphedema was detected in 14/226 (6%) of patients in the SLND group in contrast with 26/242 (11%) of cases of lymphedema in the ALND group. The patient self-assessment groups demonstrated the incidence of lymphedema in 14/253 (5%) of patients in the SLND cohort and 52/272 (19%) of women

Could radiotherapy be a contributing factor to the complications of axillary surgery? If a low incidence of ALN failures lies in sterilization of the occult metastases in the axillary lymph nodes with the conventional breast tangential ports delivering RT to a patient in a supine position (Wernicke et al., 2010), radiotherapy may be at least in part responsible for the morbidity attributable to surgery. Goodman et al reported that with the standard radiation tangents, 90% of the Berg level I axilla and up to 70% of level II axillary lymph nodes received 95% of the prescribed dose to the breast (Smitt et al., 1999). Figure 4 demonstrates a typical patient treated with 3-D radiotherapy in the supine position with the standard tangential radiation fields targeting the breast tissue and inadvertently providing at least partial coverage for at least two of the Berg axillary levels. The vast majority of literature, with only a few negative studies, supports the fact that the modern 3-D tangential radiation port of the breast, administered in supine position, will at least partially irradiate the undissected axillary lymph nodes stations (Smitt et al., 1999; Takeda et al., 2000, 2004; Krasin et al., 2000; Aristei et al., 2001; Schlembach et al., 2001; **Orecchia et al., 2005;** Wong et al., 2008; Rabinovitch et al., 2008). This phenomenon may explain why even patients with SLND experience lymphedema as a long-term toxicity [Wernicke

reporting this complication in the ALND group [Table I].

al., 2010) [Table 1].

et al., 2010].

Fig. 4. **A.** A relationship between local breast tangent radiation field and regional lymph nodes as depicted in the lateral beam's eye view with a tangential portal, where the superior border of the radiation portal is set below the heads of the clavicles (navy). **B.** The axial image through the dissected axilla demonstrates Level I (blue), Level II (purple), and Level III (dark green) axillary lymph nodal stations which are partially covered by the 90% isodose area covering the breast tissue (orange).

Does lymphedema have any risks associated with the use of systemic therapy? No significantly increased risk of incidence of lymphedema was observed in the literature with systemic therapy using hormonal treatment (Norman et al., 2010). Chemotherapy has been reported in some series to increase the complication rate associated with breast RT, including arm edema (Meek, 1998). However, no formal studies report any concrete data, which can predict such outcomes.

#### **4. Treatment of lymphedema**

#### **4.1 Non-invasive management techniques**

The main, "gold standard" of treatment for lymphedema is Combined, Complex or Comprehensive Decongestive Therapy (CDT) (Mayrovitz, 2009). The initial reductive phase of CDT treatment is known as Phase I. The main goals are to reduce the size of the affected location and to improve the skin. Phase II is known as the maintenance phase, where the patient self-manages to keep the effects of phase I treatment long term (Szuba, 2000; Hinrichs et al., 2004; Lasinski, 2002; Thomas et al., 2007; Koul et al., 2007). The effects of CDT include decreases in swelling, an increase in lymph drainage from the congested areas, a reduction in skin fibrosis and improvements in the skin conditions, an enhancement in the patient's functional status and quality of life as well as a relief in discomfort, and a reduced risk of cellulitis and Steward-Treves-Syndrome (a rare form of angiosarcoma) (Hammer et al., 2007; Mondry et al., 2004; Ferrandez, 1996; Franzcek et al., 1997; Hayes et al., 2008; Ahmed, 2008; Weiss, 2002; Kim et al., 2007; Cormier et al., 2009; Hormes et al., 2010; Fu et al., 2009; Vignes, 2006).

Components of Combined, Complex or Comprehensive Decongestive Therapy include manual lymph drainage (MLD), multi-layer, short-stretch compression bandaging, lymphatic exercise, skin care, and education in lymphedema management as well as elastic

Arm Lymphedema as a Consequence of Breast Cancer Therapy 41

After maximal volume reduction in Phase I CDT, patients will be fitted to any one of the following compression garments, depending on the affected body part: sleeves, stockings, bras, compression shorts, or face and neck compression wear. The patient will receive two compression garments one to wear and one to wash and dry. This is done to prevent wearing dirty or wet compression wear, which will promote growth of fungus and bacteria. Garments should be washed daily and replaced every 4-6 months to maintain the same compression strength. It is important the garment be properly fitted to the proper garment style and compression strength to maintain long-term control of the lymphedema in terms of volume control and skin health. Custom garments are made for those patients who cannot fit into ready-made garments and allow for special options such as reduction of risk of breakdown of skin or fastening devices for easier removal or putting on of the garment. There are both day and night or advanced day garments (Yasuhara, 1996; Badger et al., 2000; Cornu‐Thenard et al., 2007). The latter come in specialized varieties that better help to maintain the results of Phase I CDT, throughout Phase II. These include Velcro closure and specialized foam compression garments (Lund, 2000; Hafner et al., 2005; Lawrence, 2008). Seeing that lymphedema is a life-long condition, maintenance is very important (Fu et al., 2008). Self-care includes education on risk-reduction practices, self-lymph drainage, skin care, signs and symptoms of infection, proper fit and care of garments, and the importance of good nutrition, as well as healthy regiments of exercise and weight control (Farrow, 2010b). The risk of getting lymphedema increases with obesity. Therefore, it is important to maintain or lose to be at a normal, healthy weight (Gur et al., 2009; Petrek, 2001; Soran et al., 2006; Helyer et al., 2010). It has been proven that the arm volume of post-mastectomy lymphedema patients decreases in overweight patients with weight loss (Shaw et al., 2007). Other patient conditions, such as scars, musculoskeletal ailments, palliative care necessities, post-radiation fibrosis, may require alterations in the CDT program. Adaptations are additions to CDT and include therapy, scar massage or myofacial therapy (Lund, 2000;

Compression pump therapy or Intermittent Pneumatic Compression Therapy (IPC) can be used as either an adjunct to Phase I CDT or as a component of Phase II CDT. These pumps should have a individualized pattern of a multi-chamber system that stimulates lymph flow in a single direction based on the pattern and diagnosis of lymphedema. Since lymphedema is a result of a condition in a quadrant of the body as well as the limb, the pump must work to treat the condition as a whole (Shaw et al., 2007; Miranda et al., 2001; Yamazaki, 1988; Dini, 1998; Partsch, 1980; Hammond et al., 2009; Ridner et al., 2008; Szolnoky et al., 2009). Normal pump pressures range between 30-60 mmHg (Olszewski, 2009). Recent studies show possible false correlations between the skin and device interface pressure patterns. This may have an ultimate effect on therapy (Mayrovitz, 2007). Higher pressures are more dangerous because they may do harm to superficial structures (Segers et al., 2002). The length of treatment is normally 1 hour (Hammond et

Patients considered for IPC therapy need to be evaluated by a physician with medical knowledge of lymphedema. The evaluation provides level of pain and skin sensitivity as well as pressure for application to fibrotic areas. With trunk, chest or genital swelling is present, the physician must determine whether a pump that provides appliances to treat those areas is necessary or if the patient can manage the trunk swelling through self‐MLD or

Mallon, 1994; Yamamoto et al., 2008)

al., 2009; Ridner et al., 2008).

compression garments (Didem et al., 2005; Ko, 1998). There are to phases of CDT: Phase I (Reductive) and Phase II (Maintenance). The first phase's frequency and duration should be altered as to produce the best possible outcome of improvements in skin and reduction in swelling of the affected area in the shortest time period. Normally, CDT is completed within 3 to 8 weeks and administered daily, or 5 days per week (Mayrovitz, 2009; Ko, 1998; Yamamoto et al., 2008). The second phase of CDT is a self-management program is set up directly following completion of phase I. It includes self-lymph drainage, home lymphatic exercises, a skin regimen, and self-application of compression garments or bandages (Yamamoto, 2008). Phase II must be monitored and changed periodically to ensure effectiveness. This includes changing compression garments every 4-6 months and equipment replacements and maintenance. Monitoring by a medical profession is, also, essential to the long-term success for lymphedema treatment (Ko, 1998; Hafner et al., 2005; Boris et al., 1994; Johnstone et al., 2006; Lasinski, 2002).

Therapists providing CDT care are recommended by the Lymphology Association of North America® (LANA®) to have a minimum of 135 hours of training. Additional training may be required for specialists treating facial, truncal, and genital lymphedema and patients with complex diseases or illnesses (Farrow, 2010b; Czerneic et al., 2010).

Manual lymph drainage is a manual, hands-on, part of CDT care that prompts superficial lymphatic vessels to remove excess interstitial fluid which is then moved through the subepidermal fluid channels formed as a result of damage of the lymphatics (Williams et al., 2002). Certified Lymphedema therapists use the MLD technique to stimulate fluid removal from areas where the lymphatics are not working properly into working lymph vessels and nodes (McNeely, 2004).

Compression bandaging creates gradient compression by effectively utilizing multiple layers of several materials. Components of compression bandaging include tubular bandage lining, digit bandages, polyester, cotton, or foam under-cast padding, and multiple layers of short-stretch bandages with 50% overlap and 50% stretch to cover the entire limb. Shortstretch bandages stretch to 40-60% from resting length and long-stretch bandages stretch to greater than 140% of resting length. Short-stretch bandages are applied with low to moderate tension and are more prominent at the ends of extremities, reduce tissue hardening, also known as fibrosis (Farrow, 2010b; Brice et al., 2002; King, 2001; Williams, 2005; Lerner, 2000; Foldi et al., 2005)

Exercise, including lymphatic "Remedial Exercise", has been shown to have increased beneficial effects for patients with lymphedema. Patients are encouraged to create individualized exercise programs with a lymphedema specialist (Schmitz et al., 2009; Johansson et al., 2005; Mustian et al., 2009). Exercise must be done while wearing a compression garment or bandage to alleviate the build up of interstitial fluid (Gultig, 2005).

Hygiene is an important factor in lymphedema treatment which aides in reducing the amount of fungus and bacteria present on the skin. Cracks and dry skin are entry points for these pathogens and it is recommended that patients use low pH moisturizers to hydrate the skin and alleviate drying and cracking, which can lead to infections and wounds (Vaillant, 2002; Mallon, 1994). Typical infection of the skin is known as cellulitis and, ultimately, requires antibiotic treatment in people with lymphedema (Czerneic et al., 2010; Al Niaimi et al., 2009; Cooper et al., 2009; Godoy et al., 2007).

compression garments (Didem et al., 2005; Ko, 1998). There are to phases of CDT: Phase I (Reductive) and Phase II (Maintenance). The first phase's frequency and duration should be altered as to produce the best possible outcome of improvements in skin and reduction in swelling of the affected area in the shortest time period. Normally, CDT is completed within 3 to 8 weeks and administered daily, or 5 days per week (Mayrovitz, 2009; Ko, 1998; Yamamoto et al., 2008). The second phase of CDT is a self-management program is set up directly following completion of phase I. It includes self-lymph drainage, home lymphatic exercises, a skin regimen, and self-application of compression garments or bandages (Yamamoto, 2008). Phase II must be monitored and changed periodically to ensure effectiveness. This includes changing compression garments every 4-6 months and equipment replacements and maintenance. Monitoring by a medical profession is, also, essential to the long-term success for lymphedema treatment (Ko, 1998; Hafner et al., 2005;

Therapists providing CDT care are recommended by the Lymphology Association of North America® (LANA®) to have a minimum of 135 hours of training. Additional training may be required for specialists treating facial, truncal, and genital lymphedema and patients with

Manual lymph drainage is a manual, hands-on, part of CDT care that prompts superficial lymphatic vessels to remove excess interstitial fluid which is then moved through the subepidermal fluid channels formed as a result of damage of the lymphatics (Williams et al., 2002). Certified Lymphedema therapists use the MLD technique to stimulate fluid removal from areas where the lymphatics are not working properly into working lymph vessels and

Compression bandaging creates gradient compression by effectively utilizing multiple layers of several materials. Components of compression bandaging include tubular bandage lining, digit bandages, polyester, cotton, or foam under-cast padding, and multiple layers of short-stretch bandages with 50% overlap and 50% stretch to cover the entire limb. Shortstretch bandages stretch to 40-60% from resting length and long-stretch bandages stretch to greater than 140% of resting length. Short-stretch bandages are applied with low to moderate tension and are more prominent at the ends of extremities, reduce tissue hardening, also known as fibrosis (Farrow, 2010b; Brice et al., 2002; King, 2001; Williams,

Exercise, including lymphatic "Remedial Exercise", has been shown to have increased beneficial effects for patients with lymphedema. Patients are encouraged to create individualized exercise programs with a lymphedema specialist (Schmitz et al., 2009; Johansson et al., 2005; Mustian et al., 2009). Exercise must be done while wearing a compression garment or bandage to alleviate the build up of interstitial fluid (Gultig, 2005). Hygiene is an important factor in lymphedema treatment which aides in reducing the amount of fungus and bacteria present on the skin. Cracks and dry skin are entry points for these pathogens and it is recommended that patients use low pH moisturizers to hydrate the skin and alleviate drying and cracking, which can lead to infections and wounds (Vaillant, 2002; Mallon, 1994). Typical infection of the skin is known as cellulitis and, ultimately, requires antibiotic treatment in people with lymphedema (Czerneic et al., 2010; Al Niaimi et

Boris et al., 1994; Johnstone et al., 2006; Lasinski, 2002).

nodes (McNeely, 2004).

2005; Lerner, 2000; Foldi et al., 2005)

al., 2009; Cooper et al., 2009; Godoy et al., 2007).

complex diseases or illnesses (Farrow, 2010b; Czerneic et al., 2010).

After maximal volume reduction in Phase I CDT, patients will be fitted to any one of the following compression garments, depending on the affected body part: sleeves, stockings, bras, compression shorts, or face and neck compression wear. The patient will receive two compression garments one to wear and one to wash and dry. This is done to prevent wearing dirty or wet compression wear, which will promote growth of fungus and bacteria. Garments should be washed daily and replaced every 4-6 months to maintain the same compression strength. It is important the garment be properly fitted to the proper garment style and compression strength to maintain long-term control of the lymphedema in terms of volume control and skin health. Custom garments are made for those patients who cannot fit into ready-made garments and allow for special options such as reduction of risk of breakdown of skin or fastening devices for easier removal or putting on of the garment. There are both day and night or advanced day garments (Yasuhara, 1996; Badger et al., 2000; Cornu‐Thenard et al., 2007). The latter come in specialized varieties that better help to maintain the results of Phase I CDT, throughout Phase II. These include Velcro closure and specialized foam compression garments (Lund, 2000; Hafner et al., 2005; Lawrence, 2008).

Seeing that lymphedema is a life-long condition, maintenance is very important (Fu et al., 2008). Self-care includes education on risk-reduction practices, self-lymph drainage, skin care, signs and symptoms of infection, proper fit and care of garments, and the importance of good nutrition, as well as healthy regiments of exercise and weight control (Farrow, 2010b). The risk of getting lymphedema increases with obesity. Therefore, it is important to maintain or lose to be at a normal, healthy weight (Gur et al., 2009; Petrek, 2001; Soran et al., 2006; Helyer et al., 2010). It has been proven that the arm volume of post-mastectomy lymphedema patients decreases in overweight patients with weight loss (Shaw et al., 2007). Other patient conditions, such as scars, musculoskeletal ailments, palliative care necessities, post-radiation fibrosis, may require alterations in the CDT program. Adaptations are additions to CDT and include therapy, scar massage or myofacial therapy (Lund, 2000; Mallon, 1994; Yamamoto et al., 2008)

Compression pump therapy or Intermittent Pneumatic Compression Therapy (IPC) can be used as either an adjunct to Phase I CDT or as a component of Phase II CDT. These pumps should have a individualized pattern of a multi-chamber system that stimulates lymph flow in a single direction based on the pattern and diagnosis of lymphedema. Since lymphedema is a result of a condition in a quadrant of the body as well as the limb, the pump must work to treat the condition as a whole (Shaw et al., 2007; Miranda et al., 2001; Yamazaki, 1988; Dini, 1998; Partsch, 1980; Hammond et al., 2009; Ridner et al., 2008; Szolnoky et al., 2009). Normal pump pressures range between 30-60 mmHg (Olszewski, 2009). Recent studies show possible false correlations between the skin and device interface pressure patterns. This may have an ultimate effect on therapy (Mayrovitz, 2007). Higher pressures are more dangerous because they may do harm to superficial structures (Segers et al., 2002). The length of treatment is normally 1 hour (Hammond et al., 2009; Ridner et al., 2008).

Patients considered for IPC therapy need to be evaluated by a physician with medical knowledge of lymphedema. The evaluation provides level of pain and skin sensitivity as well as pressure for application to fibrotic areas. With trunk, chest or genital swelling is present, the physician must determine whether a pump that provides appliances to treat those areas is necessary or if the patient can manage the trunk swelling through self‐MLD or

Arm Lymphedema as a Consequence of Breast Cancer Therapy 43

**6. Pharmacological, complementary integrative and alternative management**  Pharmaceutical approaches to lymphedema have shown that treatment with drugs, such as Diosmin and Coumarin, or dietary supplements alone is ineffective. Diuretics cannot effectively remove interstitial fluid from the tissues, but may ultimately result in dehydration, electrolyte imbalance, or tissue damage. However patients with a history of hypertension and cardiovascular disease should speak to a healthcare provider or doctor before stopping use of diuretics (Farrow, 2010b; Loprinzi, 1999; Taylor, 1993; Cotonat, 1989). Little research from studies has proved that all natural supplements are beneficial for lymphedema patients. Selenium has been proven to aide in lymphedema as a consequence of head and neck cancers. However, bromelain and American horse chestnut have not been studied for lymphedema related specific cases. Any natural supplements should be discussed with a physician prior to ingestion (Siebert et al., 2002; Micke et al., 2003; Bruns et

Ongoing research has been presented in treatments such as cold laser, electrical stimulation, vibratory therapy, oscillation therapy, endermologie and aqualymphatic therapy and are done in combination with portions of CDT (Piller et al., 2010; Carati et al., 2003; Hafner et al., 2005; Lawrence, 2008; Tidhar et al., 201; Omar et al., 2010; Jahr, et al., 2008). Acupuncture is shown to ease some cancer and treatment related symptoms such as fatigue, hot flashes, nausea, neuropathy, and muscular or joint pain, but no formal treatment has been devised

Overall, lymphedema is a serious condition that requires timely intervention and appropriate therapy. The multidisciplinary approach is important to a patient at risk for lymphedema. It is important that early education on lymphedema be a standard of management and care for all patients. Prevention, screening, and measurement are all important for early detection of breast cancer related lymphedema. The conservative surgical approach minimizes a breast cancer patient's long-term risk of lymphedema, as does hormonal therapy. Chemotherapy, on the other hand, may have risks associated with

Aareleid T, Brenner H. Trends in cancer patient survival in Estonia before and after the

Adams,KE et al. Direct Evidence of lymphatic function improvement after advanced

Ahmed, R. J (2008) Lymphedema and Quality of Life in Breast Cancer. Survivors: The Iowa

Al Niaimi, F et al. (2009) Cellulitis and Lymphoedema, A Vicious Cycle. Journal of

Women's Health Study. Clin Oncol 26, 5689‐5696

transition from a Soviet Republic to an open-market economy. *Int. J. Cancer.* 2002;

pneumatic compression device treatment of lymphedema. Biomedical Optics

al., 2004; Cirelli, 1962; Kelly, 1996; Gaby, 1995).

from acupuncture (Farrow, 2010b).

developing lymphedema after breast cancer.

**7. Conclusions** 

**8. References** 

102, 45–50.

Express 1, 114

Lymphoedema. 4, 38‐42

garments. If a pump with only extremity attachments used, monitoring of a condition known as fibroscelerotic ring should be a must, to detect an increase in hardening of the tissue or edema above the device sleeve (Boris, 1998). If this occurs both the extremities and the trunk should be treated (Olszewski, 2009, Brice et al. 2002).

IPC should not be administered with the following conditions: acute infection, severe arterial vascular disease, acute superficial or deep vein phlebitis (inflammation or clot), recurrent cancer in the affected area, or uncompensated congestive heart failure (Farrow, 2010b).

#### **5. Invasive management techniques**

Surgical treatment for lymphedema is performed under special circumstances, when the condition's severity supersedes all possible treatment options to control it, and in unison with CDT. Surgery has been used to reduce the weight of that part of the body that suffers from the condition, minimize the recurring inflammatory attacks, improve aesthetics, and to fit the limb into garments (Gloviczki, 1999; Vignes, 2002). Several surgical options have proven to work on lymphedema patients including debulking and liposuction, tissue transfers and microsurgical lymphatic reconstruction. Debulking surgery aims at removing hard connective tissue as well as large folds of fatty tissue that presents as a consequence of the condition. After this operation patients must wear compression garments to maintain the after effects of surgery, which include lymphatic scarring and lymphatic insufficiency. However, prolonged hospitalizations, poor healing of wounds, nerve damage or loss, intense scarring, negative effects on lymphatic vessels in that limb's area, aesthetically displeasing results, and even loss of function in the limb may occur (Farrow, 2010b; Miller, 1998; Salgado et al., 20009; Kim, 2004).

Liposuction, performed under general anesthesia, is the removal of fatty tissue deposits and the creation of many small incisions in the affected body part withstanding a long history with the lymphedema condition. The fat is suctioned out by means of tubular suction devices which breaks up and liquefies it. Tight bandaging is necessary post surgery to stop bleeding and compression garments are worn life-long to prevent lymphedema recurrence due to possible scarring of the lymph vessels during the procedure. Bleeding, infection, skin loss, unordinary sensations, and recurrence may occur post-operatively (Brorson, 2003; Brorson et al., 2006; Fazhi et al., 2009). Tissue grafts, or tissue transfers, are less well known forms of surgery for effectively treating lymphedema. Their overall goal is to bring lymph vessels into congested areas for better removal of excess interstitial fluid (Fazhi et al., 2009; Slavin et al., 1999)

Microsurgical and supramicrosurgical treatments, similarly aim at draining excess lymphatic fluid by means of shuttling lymph vessels to more congested areas. Although no long-term studies have been conducted on the effectiveness of this surgery, there have been limb volume reductions and successful connections of lymph vessels and veins, lymph nodes and veins, and multiple lymph vessels (Weiss et al., 2003; Becker et al., 2006; Baumeister, 2003a, 2003b; Koshima, 2000; Chang, 2010; Campisi et al., 2006). Surgical treatment of affected lymphedema sights is risky and very rarely a necessary consideration. If surgical treatment is considered, CDT is still a necessary adjunct and compression garments and Phase II maintenance is crucial (Warren et al., 2007).

#### **6. Pharmacological, complementary integrative and alternative management**

Pharmaceutical approaches to lymphedema have shown that treatment with drugs, such as Diosmin and Coumarin, or dietary supplements alone is ineffective. Diuretics cannot effectively remove interstitial fluid from the tissues, but may ultimately result in dehydration, electrolyte imbalance, or tissue damage. However patients with a history of hypertension and cardiovascular disease should speak to a healthcare provider or doctor before stopping use of diuretics (Farrow, 2010b; Loprinzi, 1999; Taylor, 1993; Cotonat, 1989).

Little research from studies has proved that all natural supplements are beneficial for lymphedema patients. Selenium has been proven to aide in lymphedema as a consequence of head and neck cancers. However, bromelain and American horse chestnut have not been studied for lymphedema related specific cases. Any natural supplements should be discussed with a physician prior to ingestion (Siebert et al., 2002; Micke et al., 2003; Bruns et al., 2004; Cirelli, 1962; Kelly, 1996; Gaby, 1995).

Ongoing research has been presented in treatments such as cold laser, electrical stimulation, vibratory therapy, oscillation therapy, endermologie and aqualymphatic therapy and are done in combination with portions of CDT (Piller et al., 2010; Carati et al., 2003; Hafner et al., 2005; Lawrence, 2008; Tidhar et al., 201; Omar et al., 2010; Jahr, et al., 2008). Acupuncture is shown to ease some cancer and treatment related symptoms such as fatigue, hot flashes, nausea, neuropathy, and muscular or joint pain, but no formal treatment has been devised from acupuncture (Farrow, 2010b).

#### **7. Conclusions**

42 Novel Strategies in Lymphedema

garments. If a pump with only extremity attachments used, monitoring of a condition known as fibroscelerotic ring should be a must, to detect an increase in hardening of the tissue or edema above the device sleeve (Boris, 1998). If this occurs both the extremities and

IPC should not be administered with the following conditions: acute infection, severe arterial vascular disease, acute superficial or deep vein phlebitis (inflammation or clot), recurrent cancer in the affected area, or uncompensated congestive heart failure (Farrow,

Surgical treatment for lymphedema is performed under special circumstances, when the condition's severity supersedes all possible treatment options to control it, and in unison with CDT. Surgery has been used to reduce the weight of that part of the body that suffers from the condition, minimize the recurring inflammatory attacks, improve aesthetics, and to fit the limb into garments (Gloviczki, 1999; Vignes, 2002). Several surgical options have proven to work on lymphedema patients including debulking and liposuction, tissue transfers and microsurgical lymphatic reconstruction. Debulking surgery aims at removing hard connective tissue as well as large folds of fatty tissue that presents as a consequence of the condition. After this operation patients must wear compression garments to maintain the after effects of surgery, which include lymphatic scarring and lymphatic insufficiency. However, prolonged hospitalizations, poor healing of wounds, nerve damage or loss, intense scarring, negative effects on lymphatic vessels in that limb's area, aesthetically displeasing results, and even loss of function in the limb may occur (Farrow, 2010b; Miller,

Liposuction, performed under general anesthesia, is the removal of fatty tissue deposits and the creation of many small incisions in the affected body part withstanding a long history with the lymphedema condition. The fat is suctioned out by means of tubular suction devices which breaks up and liquefies it. Tight bandaging is necessary post surgery to stop bleeding and compression garments are worn life-long to prevent lymphedema recurrence due to possible scarring of the lymph vessels during the procedure. Bleeding, infection, skin loss, unordinary sensations, and recurrence may occur post-operatively (Brorson, 2003; Brorson et al., 2006; Fazhi et al., 2009). Tissue grafts, or tissue transfers, are less well known forms of surgery for effectively treating lymphedema. Their overall goal is to bring lymph vessels into congested areas for better removal of excess interstitial fluid (Fazhi et al., 2009;

Microsurgical and supramicrosurgical treatments, similarly aim at draining excess lymphatic fluid by means of shuttling lymph vessels to more congested areas. Although no long-term studies have been conducted on the effectiveness of this surgery, there have been limb volume reductions and successful connections of lymph vessels and veins, lymph nodes and veins, and multiple lymph vessels (Weiss et al., 2003; Becker et al., 2006; Baumeister, 2003a, 2003b; Koshima, 2000; Chang, 2010; Campisi et al., 2006). Surgical treatment of affected lymphedema sights is risky and very rarely a necessary consideration. If surgical treatment is considered, CDT is still a necessary adjunct and compression

garments and Phase II maintenance is crucial (Warren et al., 2007).

the trunk should be treated (Olszewski, 2009, Brice et al. 2002).

**5. Invasive management techniques** 

1998; Salgado et al., 20009; Kim, 2004).

Slavin et al., 1999)

2010b).

Overall, lymphedema is a serious condition that requires timely intervention and appropriate therapy. The multidisciplinary approach is important to a patient at risk for lymphedema. It is important that early education on lymphedema be a standard of management and care for all patients. Prevention, screening, and measurement are all important for early detection of breast cancer related lymphedema. The conservative surgical approach minimizes a breast cancer patient's long-term risk of lymphedema, as does hormonal therapy. Chemotherapy, on the other hand, may have risks associated with developing lymphedema after breast cancer.

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Salgado CJ, Sassu P, Gharb BB, et al. Radical reduction of upper extremity lymphedema with preservation of perforators. Ann Plast Surg. Sep 2009;63(2):302‐6 Schlembach PJ, Buchholz TA, Ross MI, Kirsner SM, Salas GJ, Strom EA, McNeese MD,

Schmitz, KH et al. (2009) Weight Lifting in Women with Breast‐Cancer–Related

Schumacher, M, et al. (2008)Treatment of Venous Malformations‐comparison to lymphatic

Segers P, Belgrado JP, LeDuc A, et al. Excessive pressure in multichambered cuffs used for

Shaw, S et al. (2007) A Randomized Controlled Trial of Weight Reduction as a Treatment for

Siebert U, et al. (2002) Efficacy, routine effectiveness, and safety of horsechestnut seed

Shih, Y. (2009) Incidence,Treatment Costs, and Complications of Lymphedema After Breast

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Smith B et al. (2010) Lymphedema Management in Head and Neck Cancer. Current Opinions in Otolaryngology and Head and Neck Surgery. 18,153‐158 Smitt M, Goffinet D. Utility of three-dimensional planning for axillary node coverage with breast-conserving radiation therapy: early experience. *Radiology* 1999;210:221–226. Soran, A et al. (2006) Breast Cancer Related Lymphedema‐What are the Significant Predictors and how they affect the severity of lymphedema. Breast J, 12, 536‐43 Szolnoky et al.(2009) Intermittent Pneumatic Compression Acts Synergistically With Manual Lymphatic Drainage In Complex Decongestive Therapy. Lymphology 42,188‐194 Szuba, A et al (2000) Decongestive lymphatic therapy for patients with cancer‐ related or

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Szuba, A et al. (2003) The third circulation: radionuclide lymphoscintigraphy in the

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Cancer Among Women of Working Age: A 2‐Year Follow‐Up Study. JCO 27,

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treatment‐related lymphedema. Supportive Care in Cancer, 1‐5.

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symptoms between healthy volunteers and individuals with known lymphedema


**4** 

*USA* 

**Preparing for and Coping with Breast** 

Despite recent trends indicating that new diagnoses of breast cancer have decreased slightly, the American Cancer Society estimates that there will be 207,090 new cases of invasive breast cancer and 54,010 new cases of in situ (i.e., early stage) breast cancer that are likely to have developed in 2010 (American Cancer Society, 2010). Given that the 5-year survival rate for breast cancer is now 90% and that the National Cancer Institute estimates that there were approximately 2.5 million women living in 2006 who had a history of breast cancer (American Cancer Society, 2010; Horner et al., 2009), experiencing breast cancer is increasingly about survivorship. Breast cancer survivors are at lifetime risk for developing lymphedema, a chronic condition that occurs in up to 40% of this population (Armer, Stewart, & Shook, 2009; American Cancer Society, 2007; Ferlay, Bray, Pisani, & Parkin, 2004). Lymphedema involves the accumulation of protein-rich fluid that impacts physical, functional, and psychosocial health and well-being. Second only to breast cancer recurrence, lymphedema is the most dreaded outcome of breast cancer treatment. Research has shown that women with breast cancer-related lymphedema report their most frequent action for management of lymphedema symptoms is no action (Armer & Whitman, 2002). This indicates that patient education about self-care is critical for effective self-management and risk reduction. Given the distressing and chronic nature of breast cancer-related lymphedema, there are both individual and family level psychosocial impacts related to the

This chapter is aimed at addressing real and present concerns for both patients and their family members regarding breast cancer-related lymphedema. All too often these individuals are poorly prepared to cope with the potential or actual realities of living with this physically limiting chronic condition. At the same time, many patients and family members report being both unaware that lymphedema was a possible outcome of breast cancer treatment and that medical staff, in particular oncologist and surgeons, are not well informed and/or not helpful in guiding them on how to cope. What is offered in this chapter is an overview of the condition with special attention paid to informing readers (e.g., physicians, nursing, social workers, family therapists, and others who work with patients and their families) so that they might be better equipped to serve patients and the family members. Thus, the focus of this chapter is thus two-fold: 1) patient (and family

**1. Introduction** 

onset and long-term management.

**Cancer-Related Lymphedema** 

M. Elise Radina1 and Mei R. Fu2

*1Miami University 2New York University* 


## **Preparing for and Coping with Breast Cancer-Related Lymphedema**

M. Elise Radina1 and Mei R. Fu2 *1Miami University 2New York University USA* 

#### **1. Introduction**

52 Novel Strategies in Lymphedema

Weiss M, et al (2003) Dynamic lymph flow imaging in patients with oedema of the lower

Wernicke AG, Goodman RL, Turner BC, Komarnicky LT, Curran WJ, Christos PJ, Khan I,

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Williams, AF et al (2002) A randomized controlled crossover study of manual lymphatic

Wong JS, Taghian AG, Bellon JR, Keshaviah A, Smith BL, Winer EP, Silver B, Harris JR.

results of a prospective trial. *Int J Radiat Oncol Biol Phys.* 2008;72(3):866-870. Yamamoto et al. (2008) Study of Edema Reduction Patterns During the Treatment Phase of

Yamazaki, A. (1988). Clinical experience using pneumatic massage therapy for edematous

Yasuhara, H. (1996). A study of the advantages of elastic stockings for leg lymphedema. Int

node dissection or axillary clearance. *Am J Clin Oncol* 2011 (in press). Williams, A (2005) Practical Guidance on Lymphoedema Bandaging of the Upper and

202‐206.

Ltd, 10‐14

80‐86

Angiol, 15, 272‐277

Journal of Cancer Care 11, 254–261

limbs over the last 10 years. Angilogy. 39. 154‐163.

limb for evaluation of the functional outcome after autologous lymph vessel transplantation: an 8‐year follow‐up study. Eur J Nucl Med Mol Imaging; 30,

Vandris K, Parashar B, Nori D, Chao KS. A 10 year follow up of treatment outcomes in patients with early stage breast cancer and clinically negative axillary nodes treated with tangential breast irradiation following sentinel lymph node

axillary nodes 10-years after local breast radiotherapy following sentinel lymph

Lower Extremities. In Calne, S. Editor. European Wound Management Association (EWMA). Focus Document: Lymphoedema bandaging in practice. London: MEP

drainage therapy in women with breast cancer‐related lymphoedema. European

Tangential radiotherapy without axillary surgery in early-stage breast cancer:

Complex Decongestive Physiotherapy for Extremity Lymphedema. Lymphology 41

Despite recent trends indicating that new diagnoses of breast cancer have decreased slightly, the American Cancer Society estimates that there will be 207,090 new cases of invasive breast cancer and 54,010 new cases of in situ (i.e., early stage) breast cancer that are likely to have developed in 2010 (American Cancer Society, 2010). Given that the 5-year survival rate for breast cancer is now 90% and that the National Cancer Institute estimates that there were approximately 2.5 million women living in 2006 who had a history of breast cancer (American Cancer Society, 2010; Horner et al., 2009), experiencing breast cancer is increasingly about survivorship. Breast cancer survivors are at lifetime risk for developing lymphedema, a chronic condition that occurs in up to 40% of this population (Armer, Stewart, & Shook, 2009; American Cancer Society, 2007; Ferlay, Bray, Pisani, & Parkin, 2004). Lymphedema involves the accumulation of protein-rich fluid that impacts physical, functional, and psychosocial health and well-being. Second only to breast cancer recurrence, lymphedema is the most dreaded outcome of breast cancer treatment. Research has shown that women with breast cancer-related lymphedema report their most frequent action for management of lymphedema symptoms is no action (Armer & Whitman, 2002). This indicates that patient education about self-care is critical for effective self-management and risk reduction. Given the distressing and chronic nature of breast cancer-related lymphedema, there are both individual and family level psychosocial impacts related to the onset and long-term management.

This chapter is aimed at addressing real and present concerns for both patients and their family members regarding breast cancer-related lymphedema. All too often these individuals are poorly prepared to cope with the potential or actual realities of living with this physically limiting chronic condition. At the same time, many patients and family members report being both unaware that lymphedema was a possible outcome of breast cancer treatment and that medical staff, in particular oncologist and surgeons, are not well informed and/or not helpful in guiding them on how to cope. What is offered in this chapter is an overview of the condition with special attention paid to informing readers (e.g., physicians, nursing, social workers, family therapists, and others who work with patients and their families) so that they might be better equipped to serve patients and the family members. Thus, the focus of this chapter is thus two-fold: 1) patient (and family

Preparing for and Coping with Breast Cancer-Related Lymphedema 55

relationships (Casley-Smith, 1992; Passik & McDonald, 1998; Passik, Newman, Brennan, & Tunkel, 1995; Radina, Watson, & Faubert, 2009; Thomas-MacLean, Miedema, & Tatemichi, 2005). Although women with breast cancer-related lymphedema report a variety of physical symptoms (e.g., pain, heaviness, tenderness, numbness, limited range of motion, and stiffness), arm swelling is the most common (Armer, Radina, Porock, & Culbertson, 2003; Coster, Polle, & Fallowfield, 2001; Thomas-MacLean et al., 2005). In addition, those coping with this chronic, sometimes disabling, condition are subject to frustrating physical limitations (e.g., being unable to lift heavy objects; reducing activities that require repetitive motions with the arm; keeping the arm elevated) (Radina & Armer,

Early diagnosis of breast cancer-related lymphedema remains a clinical challenge. Traditionally, lymphedema has been clinically diagnosed by healthcare professionals' observations of swelling, and has often arbitrarily been defined in research as a 2-cm increase in limb girth, a 200-mL or more increase in limb volume, or a 5% or greater limb volume change (Armer et al., 2004; Cormier et al., 2009; Stout et al., 2008). Inconsistency in the criteria defining lymphedema and the use of different measures has posed tremendous difficulty in accurately diagnosing lymphedema (Armer & Stewart, 2005). Additional contributing factors to the challenge include failure to precisely evaluate symptoms related to lymphedema, co-existing conditions, insufficient knowledge and lack of awareness among healthcare professionals. Several diagnostic approaches have been used for diagnosing breast cancer-related lymphedema, including the patient's health history and physical examination, measures of limb volume, and lymph vessle

Early and accurate diagnosis of breast cancer-related lymphedema is essential to prevent complications and achieve optimal management. A careful review of the patient's health history can promote accurate diagnosis to rule out other medical conditions that may cause similar symptoms. Such medical conditions include recurrent cancer, deep vein thrombosis, chronic venous insufficiency, diabetes, hypertension, cardiac and renal disease. These alternative diagnoses should be ruled out before establishing a diagnosis of lymphedema

A four-stage system (Table 1) can be used to facilitate physical examination to classify lymphedema in terms of skin condition and swelling (International Society of Lymphedema ([ISL], 2003). Within each stage, severity of lymphedema based on volume difference can be assessed as mild (<20% increase), moderate (20-40% increase), or severe (>40% increase). It should be noted that a clinical diagnosis of lymphedema in the current practice patterns is very often made when swelling becomes visually evident and is usually classified as "mild" lymphedema. Mild lymphedema is often defined as an initially reversible. However, by the time lymphedema is visually observable (as described in the Stage 2) it has already evolved

2001; Ridner, 2002).

imaging.

**3. Diagnosis of breast cancer-related lymphedema** 

**3.1 Health history and physical examination** 

and referring the patient for lymphedema therapy.

into the irreversible advanced stages.

member/ caregiver) education regarding strategies for early detection, risk reduction, and management/self-care and 2) individual and family level psychosocial impacts of coping with breast cancer-related lymphedema.

### **2. Defining breast cancer-related lymphedema**

Breast cancer-related lymphedema, a syndrome of abnormal swelling and multiple distressing symptoms, is a major adverse effect of breast cancer treatment (Fu & Rosedale, 2009). Lymphedema is a chronic condition involving accumulation of protein-rich fluid that impacts physical, functional, and psychosocial health and well-being (Beaulac, McNair, Scott, LaMorte, & Kavanah, 2002; Geller, Vacek, O'Brien, & Secker-Walker, 2003; Hull, 1998; Radina & Armer, 2004; Voogd et al., 2003). (Figure 1).

copyright by Mei R. Fu. All rights reserved.

Fig. 1. Example of Breast Cancer-related Lymphedema.

While the exact cause of breast cancer-related lymphedema is unknown, evidence suggests that some cancer treatments may increase the risk of developing breast cancerrelated lymphedema; risks that include the surgical removal of lymphatic vessels and nodes and the development of tissue fibrosis that sometimes follow radiation treatments, infection, or surgery (Kwan et al., 2002). Common breast cancer treatments damage and potentially weaken the lymph nodes and the vessels carrying lymph fluid, which may then compromise the effectiveness of the valves in the lymph vessels (Smith, 1998). The result is the accumulation of lymph fluid in the tissues of the arm, hand, chest, back, and neck (Berne & Levy, 1996). Changes in physical appearance and limitations created by lymphedema can affect physical and psychological health as well as interpersonal

member/ caregiver) education regarding strategies for early detection, risk reduction, and management/self-care and 2) individual and family level psychosocial impacts of coping

Breast cancer-related lymphedema, a syndrome of abnormal swelling and multiple distressing symptoms, is a major adverse effect of breast cancer treatment (Fu & Rosedale, 2009). Lymphedema is a chronic condition involving accumulation of protein-rich fluid that impacts physical, functional, and psychosocial health and well-being (Beaulac, McNair, Scott, LaMorte, & Kavanah, 2002; Geller, Vacek, O'Brien, & Secker-Walker, 2003; Hull, 1998;

While the exact cause of breast cancer-related lymphedema is unknown, evidence suggests that some cancer treatments may increase the risk of developing breast cancerrelated lymphedema; risks that include the surgical removal of lymphatic vessels and nodes and the development of tissue fibrosis that sometimes follow radiation treatments, infection, or surgery (Kwan et al., 2002). Common breast cancer treatments damage and potentially weaken the lymph nodes and the vessels carrying lymph fluid, which may then compromise the effectiveness of the valves in the lymph vessels (Smith, 1998). The result is the accumulation of lymph fluid in the tissues of the arm, hand, chest, back, and neck (Berne & Levy, 1996). Changes in physical appearance and limitations created by lymphedema can affect physical and psychological health as well as interpersonal

with breast cancer-related lymphedema.

copyright by Mei R. Fu. All rights reserved.

Fig. 1. Example of Breast Cancer-related Lymphedema.

**2. Defining breast cancer-related lymphedema** 

Radina & Armer, 2004; Voogd et al., 2003). (Figure 1).

relationships (Casley-Smith, 1992; Passik & McDonald, 1998; Passik, Newman, Brennan, & Tunkel, 1995; Radina, Watson, & Faubert, 2009; Thomas-MacLean, Miedema, & Tatemichi, 2005). Although women with breast cancer-related lymphedema report a variety of physical symptoms (e.g., pain, heaviness, tenderness, numbness, limited range of motion, and stiffness), arm swelling is the most common (Armer, Radina, Porock, & Culbertson, 2003; Coster, Polle, & Fallowfield, 2001; Thomas-MacLean et al., 2005). In addition, those coping with this chronic, sometimes disabling, condition are subject to frustrating physical limitations (e.g., being unable to lift heavy objects; reducing activities that require repetitive motions with the arm; keeping the arm elevated) (Radina & Armer, 2001; Ridner, 2002).

#### **3. Diagnosis of breast cancer-related lymphedema**

Early diagnosis of breast cancer-related lymphedema remains a clinical challenge. Traditionally, lymphedema has been clinically diagnosed by healthcare professionals' observations of swelling, and has often arbitrarily been defined in research as a 2-cm increase in limb girth, a 200-mL or more increase in limb volume, or a 5% or greater limb volume change (Armer et al., 2004; Cormier et al., 2009; Stout et al., 2008). Inconsistency in the criteria defining lymphedema and the use of different measures has posed tremendous difficulty in accurately diagnosing lymphedema (Armer & Stewart, 2005). Additional contributing factors to the challenge include failure to precisely evaluate symptoms related to lymphedema, co-existing conditions, insufficient knowledge and lack of awareness among healthcare professionals. Several diagnostic approaches have been used for diagnosing breast cancer-related lymphedema, including the patient's health history and physical examination, measures of limb volume, and lymph vessle imaging.

#### **3.1 Health history and physical examination**

Early and accurate diagnosis of breast cancer-related lymphedema is essential to prevent complications and achieve optimal management. A careful review of the patient's health history can promote accurate diagnosis to rule out other medical conditions that may cause similar symptoms. Such medical conditions include recurrent cancer, deep vein thrombosis, chronic venous insufficiency, diabetes, hypertension, cardiac and renal disease. These alternative diagnoses should be ruled out before establishing a diagnosis of lymphedema and referring the patient for lymphedema therapy.

A four-stage system (Table 1) can be used to facilitate physical examination to classify lymphedema in terms of skin condition and swelling (International Society of Lymphedema ([ISL], 2003). Within each stage, severity of lymphedema based on volume difference can be assessed as mild (<20% increase), moderate (20-40% increase), or severe (>40% increase). It should be noted that a clinical diagnosis of lymphedema in the current practice patterns is very often made when swelling becomes visually evident and is usually classified as "mild" lymphedema. Mild lymphedema is often defined as an initially reversible. However, by the time lymphedema is visually observable (as described in the Stage 2) it has already evolved into the irreversible advanced stages.

Preparing for and Coping with Breast Cancer-Related Lymphedema 57

**The following questions are about symptoms in your affected arm, hand, breast, axilla (under arm), or chest today or in the past three months.** 

> A little 1

0

Copyright 2006-2009 College of Nursing, New York University. Contact Mei R. Fu, PhD, RN, ACNS-

Table 2. Example of Symptom Checklist - Breast Cancer & Lymphedema Symptom

**Have you had \_\_\_?** No

1. Shoulder 2. Elbow 3. Wrist 4. Fingers 5. Arm

6. Hand or arm swelling

12. Toughness or thickness of skin

15. Hotness/increased temperature

7. Breast swelling 8. Chest wall swelling

9. Firmness

10. Tightness 11. Heaviness

13. Stiffness 14. Tenderness

16. Redness

17. Blistering

19. Numbness 20. Burning 21. Stabbing

Experience Index

18. Pain/aching/soreness

22. Tingling (pins and needles)

BC; Telephone: 212-998-5314; Email: mf67@nyu.edu

23. Arm or hand fatigue 24. Arm or hand weakness **How Severe?** 

Quite a bit 3

Very Severe 4

Somewhat 2


Table 1. Staging of Lymphedema (International Society of Lymphedema ([ISL], 2003)

Symptom assessment is essential since very often observable swelling and measurable volume changes are absent during the initial development of lymphedema, but patients may report such symptoms as heaviness, tightness, firmness, pain, or numbness (Cormier et al., 2009; Fu & Rosedale, 2009). These symptoms may be the earliest indicator of increasing interstitial pressure changes associated with lymphedema (Kosir et al., 2001). As the fluid increases, the limb may become visibly swollen with an observable increase in limb size. Recent research shows that limb volume change (LVC) by the infra-red perometer has significantly increased as breast cancer survivors' reports of swelling, heaviness, tenderness, firmness, tightness, and aching have increased (Cormier et al., 2009). On average, breast cancer survivors reported 4.2 symptoms for survivors with <5.0% LVC; 5.5 symptoms for 5.0-9.9% LVC, 7.0 symptoms for 10.0-14.9% LVC, and 12.5 symptoms for > 15% LVC, respectively (p<0.001) (Cormier et al., 2009). Because early intervention is believed to yield better patient outcomes, the presence of lymphedema symptoms should warrant institution of early interventions (Armer, Radina, Porock, & Culbertson, 2003; Armer et al., 2004; Foeldi et al., 2003). In addition, experience of symptoms has elicited tremendous distress in breast cancer survivors and exerted negative impact on their quality of lives (Fu & Rosedale 2009; Pyszel et al., 2006). Symptoms should be one of the major patient-centered clinical outcomes for evaluating the effectiveness of lymphedema treatment (Armer et al., 2005; Sitzia, Stanton, & Badger, 1997). A symptom checklist (Table 2) may be used for symptom assessment.

No pitting

A feeling of heaviness

swelling occurs

Visible swelling

affected limb

skin

Existing months or years before overt

Hardened and thickened tissue

Enlarged and obvious swelling of the

Hardness, thickness, and toughness of

Lymph leaking through damaged skin

Stages Presentations

0 Latent or sub-clinical condition No noticeable swelling

i. Early accumulation of lymph fluid Pitting swelling

ii. Increased or chronic swelling Pitting swelling

assessment.

iii.Lymphostatic elephantiasis Absence of pitting swelling

Table 1. Staging of Lymphedema (International Society of Lymphedema ([ISL], 2003)

Symptom assessment is essential since very often observable swelling and measurable volume changes are absent during the initial development of lymphedema, but patients may report such symptoms as heaviness, tightness, firmness, pain, or numbness (Cormier et al., 2009; Fu & Rosedale, 2009). These symptoms may be the earliest indicator of increasing interstitial pressure changes associated with lymphedema (Kosir et al., 2001). As the fluid increases, the limb may become visibly swollen with an observable increase in limb size. Recent research shows that limb volume change (LVC) by the infra-red perometer has significantly increased as breast cancer survivors' reports of swelling, heaviness, tenderness, firmness, tightness, and aching have increased (Cormier et al., 2009). On average, breast cancer survivors reported 4.2 symptoms for survivors with <5.0% LVC; 5.5 symptoms for 5.0-9.9% LVC, 7.0 symptoms for 10.0-14.9% LVC, and 12.5 symptoms for > 15% LVC, respectively (p<0.001) (Cormier et al., 2009). Because early intervention is believed to yield better patient outcomes, the presence of lymphedema symptoms should warrant institution of early interventions (Armer, Radina, Porock, & Culbertson, 2003; Armer et al., 2004; Foeldi et al., 2003). In addition, experience of symptoms has elicited tremendous distress in breast cancer survivors and exerted negative impact on their quality of lives (Fu & Rosedale 2009; Pyszel et al., 2006). Symptoms should be one of the major patient-centered clinical outcomes for evaluating the effectiveness of lymphedema treatment (Armer et al., 2005; Sitzia, Stanton, & Badger, 1997). A symptom checklist (Table 2) may be used for symptom


Copyright 2006-2009 College of Nursing, New York University. Contact Mei R. Fu, PhD, RN, ACNS-BC; Telephone: 212-998-5314; Email: mf67@nyu.edu

Table 2. Example of Symptom Checklist - Breast Cancer & Lymphedema Symptom Experience Index

Preparing for and Coping with Breast Cancer-Related Lymphedema 59

Water displacement is seldom used in clinical settings because of cumbersome spillover and hygienic concerns (Armer & Stewart, 2005; Gerber, 1998). Patients submerge the affected arm in a container filled with water and the overflow of water is caught in another container and weighed (Figure 3). This method does not provide data about localization of swelling or shape of the extremity (Petlund, 1991; Tierney et al., 1996). The method is contraindicated in patients with open skin lesions. Patients may find it difficult to hold the position for the time

copyright by Jane Armer. All rights reserved.

needed for the tank overflow to drain.

copyright by Jane Armer. All rights reserved.

Fig. 3. Water Displacement

**3.2.2 Water displacement** 

Fig. 2. Sequential Circumferential Arm Measurements

Physical examination and symptom assessment can also help to differentiate if the onset of lymphedema following breast cancer treatment is gradual or sudden (Fu et al., 2009). It is still not fully understood why some patients are more prone to fluid build-up than others even with similarity in surgical treatment, numbers of lymph nodes removed, chemotherapy and radiotherapy. With gradual onset, noticeable swelling is often absent initially, but patients may report feelings of tightness and heaviness in the previous year, visible and measurable lymphedema typically occurs two to five years after treatment, but it can also happen as many as 15 to 30 years later (Armer et al., 2003; Petrek, Senie, Peters, & Rosen, 2001). With sudden onset, swelling develops rapidly, usually within 24 hours and often breast cancer survivors are able to identify the triggers, such as air travel, infection, or injuries (e.g., cuts, insect bites, pinpricks, burns) (Fu & Rosedale, 2009; Johansson, et al., 2002; Petrek et al., 2001). With infection (especially cellulitis) or injuries, breast cancer survivors usually experience sudden swelling with redness, elevated white blood cells, or elevated temperature (Foeldi et al., 2003). Very often, immediate administration of oral or IV antibiotics can clear the infection, while elevation of the limb helps to reduce the swelling. It is possible that early stage lymphedema (Stage 1 and 2) may continue to exist in a latent or sub-clinical state even when successfully treated at initial onset, sometimes presenting at later stages ten or more years after initial diagnosis of sudden onset of lymphedema (Brennan & Miller, 1998).

#### **3.2 Measures of limb volume (LV)**

Measuring LV is an objective way to quantifying lymphedema. However, quantifying lymphedema is a challenge because various measurement approaches have been used to define lymphedema and certain types of breast cancer-related lymphedema such as breast, shoulder, and truncal lymphedema cannot be quantified with current measurement technology. Methods of measuring limb volume LV include sequential circumference limb measurement, water displacement, infra-red perometry, and bioimpedance spectroscopy (Armer & Stewart, 2005; Petlund, 1991; Tierney, Aslam, Rennie, & Grace, 1996; Cornish, et al., 2001).

#### **3.2.1 Sequential circumferential arm measurements**

Measuring circumference is the most widely used diagnostic method. A flexible non-stretch tape measure for circumferences is usually used to assure consistent tension over soft tissue, muscle, and bony prominences (Armer et al., 2004; Petlund, 1991). Measurements are done on both affected and non-affected limbs at the hand proximal to the metacarpals, wrist, and then every 4 cm from the wrist to axilla or at minimum, six measurements are recommended: circumference at the mid‐hand, wrist, elbow, upper arm just below the axilla, and at 10cm distal to and proximal to the lateral epicondyle on both arms (Armer et al., 2004; Callaway et al., 1988) The most common criterion for diagnosis has been a finding of ≥ 2 cm or >200 ml difference in limb volume as compared to the non-affected limb or 10% volume differences in the affected limb (Armer et al., 2004; Armer & Stewart, 2005; Mayrovitz, Simms, & MacDonald, 2000; Stanton et al., 2009).

Circumferential limb measurement has limited inter- and intra-rater reliability and costly in terms of training time and clinician's time for measurement (Armer & Stewart, 2005; Gerber, 1998). (Figure 2).

copyright by Jane Armer. All rights reserved.

Fig. 2. Sequential Circumferential Arm Measurements

#### **3.2.2 Water displacement**

58 Novel Strategies in Lymphedema

Physical examination and symptom assessment can also help to differentiate if the onset of lymphedema following breast cancer treatment is gradual or sudden (Fu et al., 2009). It is still not fully understood why some patients are more prone to fluid build-up than others even with similarity in surgical treatment, numbers of lymph nodes removed, chemotherapy and radiotherapy. With gradual onset, noticeable swelling is often absent initially, but patients may report feelings of tightness and heaviness in the previous year, visible and measurable lymphedema typically occurs two to five years after treatment, but it can also happen as many as 15 to 30 years later (Armer et al., 2003; Petrek, Senie, Peters, & Rosen, 2001). With sudden onset, swelling develops rapidly, usually within 24 hours and often breast cancer survivors are able to identify the triggers, such as air travel, infection, or injuries (e.g., cuts, insect bites, pinpricks, burns) (Fu & Rosedale, 2009; Johansson, et al., 2002; Petrek et al., 2001). With infection (especially cellulitis) or injuries, breast cancer survivors usually experience sudden swelling with redness, elevated white blood cells, or elevated temperature (Foeldi et al., 2003). Very often, immediate administration of oral or IV antibiotics can clear the infection, while elevation of the limb helps to reduce the swelling. It is possible that early stage lymphedema (Stage 1 and 2) may continue to exist in a latent or sub-clinical state even when successfully treated at initial onset, sometimes presenting at later stages ten or more years after initial diagnosis of sudden onset of lymphedema

Measuring LV is an objective way to quantifying lymphedema. However, quantifying lymphedema is a challenge because various measurement approaches have been used to define lymphedema and certain types of breast cancer-related lymphedema such as breast, shoulder, and truncal lymphedema cannot be quantified with current measurement technology. Methods of measuring limb volume LV include sequential circumference limb measurement, water displacement, infra-red perometry, and bioimpedance spectroscopy (Armer & Stewart, 2005;

Measuring circumference is the most widely used diagnostic method. A flexible non-stretch tape measure for circumferences is usually used to assure consistent tension over soft tissue, muscle, and bony prominences (Armer et al., 2004; Petlund, 1991). Measurements are done on both affected and non-affected limbs at the hand proximal to the metacarpals, wrist, and then every 4 cm from the wrist to axilla or at minimum, six measurements are recommended: circumference at the mid‐hand, wrist, elbow, upper arm just below the axilla, and at 10cm distal to and proximal to the lateral epicondyle on both arms (Armer et al., 2004; Callaway et al., 1988) The most common criterion for diagnosis has been a finding of ≥ 2 cm or >200 ml difference in limb volume as compared to the non-affected limb or 10% volume differences in the affected limb (Armer et al., 2004; Armer & Stewart, 2005;

Circumferential limb measurement has limited inter- and intra-rater reliability and costly in terms of training time and clinician's time for measurement (Armer & Stewart, 2005; Gerber,

Petlund, 1991; Tierney, Aslam, Rennie, & Grace, 1996; Cornish, et al., 2001).

**3.2.1 Sequential circumferential arm measurements** 

Mayrovitz, Simms, & MacDonald, 2000; Stanton et al., 2009).

(Brennan & Miller, 1998).

1998). (Figure 2).

**3.2 Measures of limb volume (LV)** 

Water displacement is seldom used in clinical settings because of cumbersome spillover and hygienic concerns (Armer & Stewart, 2005; Gerber, 1998). Patients submerge the affected arm in a container filled with water and the overflow of water is caught in another container and weighed (Figure 3). This method does not provide data about localization of swelling or shape of the extremity (Petlund, 1991; Tierney et al., 1996). The method is contraindicated in patients with open skin lesions. Patients may find it difficult to hold the position for the time needed for the tank overflow to drain.

 copyright by Jane Armer. All rights reserved. Fig. 3. Water Displacement

Preparing for and Coping with Breast Cancer-Related Lymphedema 61

to determine arm lymphedema. Ratio means of 1.139 for at-risk dominant arms and 1.066 for at-risk non-dominant arms are indicators of arm lymphedema. The Imp XCA® uses the impedance ratio values to calculate a *Lymphedema Index [L-Dex]*. The L-Dex scale ranges from -10 to +10, which is equivalent to the impedance ratio from 0.935 to 1.139 for at-risk dominant arms and 0.862 to 1.066 for at-risk non-dominant arms, respectively. Each one standard unit in L-Dex is equivalent to the impedance ratio of 0.03. A patient is determined to have arm lymphedema or arm swelling if the patient's L-Dex exceeds the normal value of +10, i.e. exceed impedance ratio means of 1.139 for at-risk dominant arms and 1.066 for atrisk non-dominant arms, respectively (44). Measurement of arms takes less than five minutes when using the Imp-XCA® and results are immediately available to clinicians. However, the Imp XCA® is only capable of assessing unilateral lymphedema, unable to provide data about localization of swelling or shape of the extremity, and cannot be applied to patients with renal or heart failure, cardiac pacemaker or defibrillator, inability to lying down on the exam table, artificial limbs, or pregnancy as accurate measurement of lymphedema may not be possible. Continuous cost for electrodes is needed. (Figure 4).

Lymphoscintigraphy (isotope lymphography) can ensure definite lymphedema diagnosis (Mortimer, 2003; Cambria et al., 1993). Lymphoscintigraphy employs a nuclear medicine to visualize the lymph vessel. With the patient supine, a radiolabelled macromolecular tracer (Tc-99m filtered [0.22 milli micron] or unfiltered sulfur colloid) is injected intradermally within one of the interdigital spaces of the affected limb using a 25-gauge needle in a 1 ml

 copyright by Mei R. Fu. All rights reserved. Fig. 5. Bioimpedance Spectroscopy (BIS).

**3.3 Lymph vessel imaging** 

#### **3.2.3 Infra-red perometry**

The advent of infra-red perometry (also called optoelectronic volumetry), such as the perometer 350S (Juzo, Cuyahoga Falls, OH), enables reliable and accurate detection of 3% limb volume change (LVC) (Cormier et al., 2009; Stout et al., 2008). The perometer works in much the same manner as computed tomography but uses infrared light instead of X-rays (Petlund, 1991). There is no toxic effect to the patient. Perometry is performed on each arm as it is held horizontally with the patient standing comfortably (Figure 4). The perometer maps a 3-dimensional graph of the affected and non-affected extremities using numerous rectilinear light beams, and interfaces with a computer for data analysis and storage. A 3 dimensional limb image is generated and LV is calculated. This optoelectronic method has a standard deviation of 8.9 ml (arm), less than 0.5% of LV with repeated measuring (Armer & Stewart, 2005; Cormier et al., 2009). Because the perometer is capable of measuring bilateral lymphedema and localization of swelling as well as detecting a 3% LVC that enables detectable differences in quality of life (QOL) and symptom reporting, the optimal measure for lymphedema is the evaluation of LVC by the perometer (Armer & Stewart, 2005; Cormier et al., 2009; Stout et al., 2008).

copyright by Mei R. Fu. All rights reserved.

Fig. 4. Infra-red Perometry

#### **3.2.4 Bioimpedance spectroscopy (BIS)**

Bioelectrical impedance has been used to detect onset lymphedema and monitor results of lymphatic massage in clinical settings (Cornish, et al., 2001; Ridner, Montgomery, Hepworth, Stewart, & Armer, 2007; Ward, Bunce, Cornish, Mirolo, Thomas, & Jones, 1992; Ward, Essex, & Cornish, 2006). The Imp XCA® (Impedimed, Brisbane, Australia) uses a single frequency below 30 kHz to measure impedance and resistance of the extracellular fluid. The device uses the impedance ratio values between the unaffected and affected limb

The advent of infra-red perometry (also called optoelectronic volumetry), such as the perometer 350S (Juzo, Cuyahoga Falls, OH), enables reliable and accurate detection of 3% limb volume change (LVC) (Cormier et al., 2009; Stout et al., 2008). The perometer works in much the same manner as computed tomography but uses infrared light instead of X-rays (Petlund, 1991). There is no toxic effect to the patient. Perometry is performed on each arm as it is held horizontally with the patient standing comfortably (Figure 4). The perometer maps a 3-dimensional graph of the affected and non-affected extremities using numerous rectilinear light beams, and interfaces with a computer for data analysis and storage. A 3 dimensional limb image is generated and LV is calculated. This optoelectronic method has a standard deviation of 8.9 ml (arm), less than 0.5% of LV with repeated measuring (Armer & Stewart, 2005; Cormier et al., 2009). Because the perometer is capable of measuring bilateral lymphedema and localization of swelling as well as detecting a 3% LVC that enables detectable differences in quality of life (QOL) and symptom reporting, the optimal measure for lymphedema is the evaluation of LVC by the perometer (Armer & Stewart, 2005;

Bioelectrical impedance has been used to detect onset lymphedema and monitor results of lymphatic massage in clinical settings (Cornish, et al., 2001; Ridner, Montgomery, Hepworth, Stewart, & Armer, 2007; Ward, Bunce, Cornish, Mirolo, Thomas, & Jones, 1992; Ward, Essex, & Cornish, 2006). The Imp XCA® (Impedimed, Brisbane, Australia) uses a single frequency below 30 kHz to measure impedance and resistance of the extracellular fluid. The device uses the impedance ratio values between the unaffected and affected limb

**3.2.3 Infra-red perometry** 

Cormier et al., 2009; Stout et al., 2008).

copyright by Mei R. Fu. All rights reserved.

**3.2.4 Bioimpedance spectroscopy (BIS)** 

Fig. 4. Infra-red Perometry

to determine arm lymphedema. Ratio means of 1.139 for at-risk dominant arms and 1.066 for at-risk non-dominant arms are indicators of arm lymphedema. The Imp XCA® uses the impedance ratio values to calculate a *Lymphedema Index [L-Dex]*. The L-Dex scale ranges from -10 to +10, which is equivalent to the impedance ratio from 0.935 to 1.139 for at-risk dominant arms and 0.862 to 1.066 for at-risk non-dominant arms, respectively. Each one standard unit in L-Dex is equivalent to the impedance ratio of 0.03. A patient is determined to have arm lymphedema or arm swelling if the patient's L-Dex exceeds the normal value of +10, i.e. exceed impedance ratio means of 1.139 for at-risk dominant arms and 1.066 for atrisk non-dominant arms, respectively (44). Measurement of arms takes less than five minutes when using the Imp-XCA® and results are immediately available to clinicians. However, the Imp XCA® is only capable of assessing unilateral lymphedema, unable to provide data about localization of swelling or shape of the extremity, and cannot be applied to patients with renal or heart failure, cardiac pacemaker or defibrillator, inability to lying down on the exam table, artificial limbs, or pregnancy as accurate measurement of lymphedema may not be possible. Continuous cost for electrodes is needed. (Figure 4).

 copyright by Mei R. Fu. All rights reserved. Fig. 5. Bioimpedance Spectroscopy (BIS).

#### **3.3 Lymph vessel imaging**

Lymphoscintigraphy (isotope lymphography) can ensure definite lymphedema diagnosis (Mortimer, 2003; Cambria et al., 1993). Lymphoscintigraphy employs a nuclear medicine to visualize the lymph vessel. With the patient supine, a radiolabelled macromolecular tracer (Tc-99m filtered [0.22 milli micron] or unfiltered sulfur colloid) is injected intradermally within one of the interdigital spaces of the affected limb using a 25-gauge needle in a 1 ml

Preparing for and Coping with Breast Cancer-Related Lymphedema 63

Pneumatic compression therapy, also known as compression pump therapy, can be used daily for 30-60 minutes during the maintenance phase of CDT. Acceptable pneumatic compression device (PCD) should have multiple chambers delivering a sequential pressure. Caution must be used, however, because compression pumps can damage the vasculature. Furthermore, compression devices are contraindicated in patients with congestive heart failure, active infection, or deep venous thrombosis (Rockson et al., 1998). The recently developed PCD such as the Flexitouch® system is believed to be safer than the older PCD (Ridner et al., 2010). The Flexitouch® system is an advanced, programmable PCD that is cleared by the Food and Drug Administration for home use. This device is the only PCD designed to emulate the therapeutic techniques of MLD. Published studies and case reports suggest that breast cancer-related limb and truncal lymphedema may be effectively treated with the Flexitouch® system since the device includes garments to treat truncal swelling

Therapeutic exercises are individualized remedial exercises that consist of cardiovascular exercises, stretching, aerobic activity, and strength training. Therapeutic exercise is believed to increase lymph flow and protein absorption through repeated contraction and relaxation of muscles. Therapeutic exercise should be initiated by well-trained lymphedema therapists and then continued at home. One randomized controlled trial found that a 6-month intervention did not increase risk or add to symptoms of lymphedema (Ahmed et al., 2006). Other data also indicate that exercise as an individual therapy is neither a contraindication after breast cancer treatment nor does it decrease the risk of developing lymphedema (Ahmed et al., 2006; Schmitz et al., 2009; Johansson et al., 2005). For survivors with lymphedema, compression garments or compression bandages must be worn during exercise to counterbalance the buildup of interstitial fluid (Schmitz et al., 2009; Johansson et

Surgical approaches are performed to debulk tissue or to divert lymphatic drainage (Casley-Smith, 1992; Cormier et al., 2011). Surgical treatment for breast cancer-related lymphedema is rarely performed except in severe and refractory cases to reduce the weight of the lymphedematous region, minimize the frequency of infectious and inflammatory episodes, and improve cosmesis and function. Surgical treatment includes: (1) excisional operations (e.g., debulking, amputation, and liposuction), (2) lymphatic reconstruction, and (3) tissue transfer procedures (e.g., lymph node transplantation, pedicled omentum, bone marrow stromal cell transplantation) (Cormier et al., 2011). For severe lymphedema, excisional operations and debulking procedures have been reported as effective methods to alleviate symptoms by removing fibrosclerotic connective tissue, excess adipose tissue, and excess skin. Various microsurgical techniques for lymphatic reconstruction have been attempted since the early 1960s, including the creation of anastomoses between lymphatic channels and adjacent veins, between lymph nodes and veins, and between distal and proximal lymphatics (Campisi et al., 2001; O'Brien et al., 1990). Lympho-lymphatic anastomosis and

**4.2 Pneumatic compression therapy** 

(Ridner et al., 2010).

al., 2005).

**4.4 Surgery** 

**4.3 Therapeutic exercises** 

syringe (Cambria et al., 1993; Partsch, 1995; Ter et al., 1993). The injection is given between the index and middle finger in the web space for the upper limbs. Both sides are done simultaneously so that the affected limb can be compared to the unaffected limb. The lymphatic transport of the macromolecule is tracked with a gamma camera, and the rate of tracer disappearance from the injection site and the accumulation of counts within the lymph node are both quantified. Typical abnormalities observed in lymphedema include dermal backflow, absent or delayed transport of tracer, cross-over filling with retrograde backflow, and either absent or delayed visualization of the lymph nodes (Cambria et al., 1993; Partsch, 1995; Ter et al., 1993). However, lymphography is now rarely used in patients because of its potential to cause lymphatic injury and its inability to clarify function (Meek, 1998; Mortimer, 2003).

#### **4. Treatment of breast cancer-related lymphedema**

Treatment of lymphedema has been and continues to be a major healthcare challenge since no treatment can cure this chronic condition. Lymphedema treatment refers to therapies applied to help to slow the disease progression by reducing or maintaining swelling and relieving symptoms. Lymphedema therapy includes complete decongestive physiotherapy, pneumatic compression therapy (PCT), therapeutic exercises, surgery, and pharmacological therapy (Fu, 2005; Geller, Vacek, O'Brien, & Secker-Walker, 2003; ISL, 2003; Megens & Harris, 1998).

#### **4.1 Complete decongestive therapy (CDT)**

Complete decongestive therapy (also known as *complex decompressive physiotherapy, comprehensive decongestive treatment,* and *multimodal physical therapy*) is the standard of care for breast cancer-related lymphedema. CDT includes an initial reductive treatment phase followed by an ongoing maintenance phase. The reductive treatment phase involves 2-5 sessions per week for 3 to 8 weeks in a specialized lymphedema clinic until the reduction of fluid volume has reached a plateau. The reductive treatment phase of CDT consists of multiple components, including manual lymph drainage (MLD), multilayer, short-stretch compression bandaging, therapeutic exercise, skin care, education in self-management, and elastic compression garments (Davis, 1998; Megens & Harris, 1998). The reductive treatment phase should be reinstituted whenever swelling is exacerbated or whenever symptoms are worsened. Once the reductive treatment phase is completed, the maintenance phase starts in which the patient continues self-management with skin care and exercise, self MLD, and use of a compressive sleeve and gauntlet during the day and arm bandaging at night (Davis, 1998; Megens & Harris, 1998). The maintenance phase of CDT requires a lifelong self-management program with self MLD, exercise, skin care, and compression garments or bandages. Long-term volume reduction is as high as 50-63% in up to 79% of patients who are 100% compliant (Boris et al., 1997; Erickson et al., 2001; Foeldi et al., 2003; Rinerhart-Ayres, 1998). Yet, compliance with the prescribed selfmanagement regimen during the maintenance phase is difficult for breast cancer survivors (Brennan & Miller, 1998; Fu, 2010). From the patient's perspective, the treatment for lymphedema itself is a constant reminder that prevents survivors from living a normal life (Fu, 2005; Fu & Rosedale, 2009).

#### **4.2 Pneumatic compression therapy**

62 Novel Strategies in Lymphedema

syringe (Cambria et al., 1993; Partsch, 1995; Ter et al., 1993). The injection is given between the index and middle finger in the web space for the upper limbs. Both sides are done simultaneously so that the affected limb can be compared to the unaffected limb. The lymphatic transport of the macromolecule is tracked with a gamma camera, and the rate of tracer disappearance from the injection site and the accumulation of counts within the lymph node are both quantified. Typical abnormalities observed in lymphedema include dermal backflow, absent or delayed transport of tracer, cross-over filling with retrograde backflow, and either absent or delayed visualization of the lymph nodes (Cambria et al., 1993; Partsch, 1995; Ter et al., 1993). However, lymphography is now rarely used in patients because of its potential to cause lymphatic injury and its inability to clarify function (Meek,

Treatment of lymphedema has been and continues to be a major healthcare challenge since no treatment can cure this chronic condition. Lymphedema treatment refers to therapies applied to help to slow the disease progression by reducing or maintaining swelling and relieving symptoms. Lymphedema therapy includes complete decongestive physiotherapy, pneumatic compression therapy (PCT), therapeutic exercises, surgery, and pharmacological therapy (Fu, 2005; Geller, Vacek, O'Brien, & Secker-Walker, 2003; ISL, 2003; Megens &

Complete decongestive therapy (also known as *complex decompressive physiotherapy, comprehensive decongestive treatment,* and *multimodal physical therapy*) is the standard of care for breast cancer-related lymphedema. CDT includes an initial reductive treatment phase followed by an ongoing maintenance phase. The reductive treatment phase involves 2-5 sessions per week for 3 to 8 weeks in a specialized lymphedema clinic until the reduction of fluid volume has reached a plateau. The reductive treatment phase of CDT consists of multiple components, including manual lymph drainage (MLD), multilayer, short-stretch compression bandaging, therapeutic exercise, skin care, education in self-management, and elastic compression garments (Davis, 1998; Megens & Harris, 1998). The reductive treatment phase should be reinstituted whenever swelling is exacerbated or whenever symptoms are worsened. Once the reductive treatment phase is completed, the maintenance phase starts in which the patient continues self-management with skin care and exercise, self MLD, and use of a compressive sleeve and gauntlet during the day and arm bandaging at night (Davis, 1998; Megens & Harris, 1998). The maintenance phase of CDT requires a lifelong self-management program with self MLD, exercise, skin care, and compression garments or bandages. Long-term volume reduction is as high as 50-63% in up to 79% of patients who are 100% compliant (Boris et al., 1997; Erickson et al., 2001; Foeldi et al., 2003; Rinerhart-Ayres, 1998). Yet, compliance with the prescribed selfmanagement regimen during the maintenance phase is difficult for breast cancer survivors (Brennan & Miller, 1998; Fu, 2010). From the patient's perspective, the treatment for lymphedema itself is a constant reminder that prevents survivors from living a normal

1998; Mortimer, 2003).

Harris, 1998).

**4. Treatment of breast cancer-related lymphedema** 

**4.1 Complete decongestive therapy (CDT)** 

life (Fu, 2005; Fu & Rosedale, 2009).

Pneumatic compression therapy, also known as compression pump therapy, can be used daily for 30-60 minutes during the maintenance phase of CDT. Acceptable pneumatic compression device (PCD) should have multiple chambers delivering a sequential pressure. Caution must be used, however, because compression pumps can damage the vasculature. Furthermore, compression devices are contraindicated in patients with congestive heart failure, active infection, or deep venous thrombosis (Rockson et al., 1998). The recently developed PCD such as the Flexitouch® system is believed to be safer than the older PCD (Ridner et al., 2010). The Flexitouch® system is an advanced, programmable PCD that is cleared by the Food and Drug Administration for home use. This device is the only PCD designed to emulate the therapeutic techniques of MLD. Published studies and case reports suggest that breast cancer-related limb and truncal lymphedema may be effectively treated with the Flexitouch® system since the device includes garments to treat truncal swelling (Ridner et al., 2010).

#### **4.3 Therapeutic exercises**

Therapeutic exercises are individualized remedial exercises that consist of cardiovascular exercises, stretching, aerobic activity, and strength training. Therapeutic exercise is believed to increase lymph flow and protein absorption through repeated contraction and relaxation of muscles. Therapeutic exercise should be initiated by well-trained lymphedema therapists and then continued at home. One randomized controlled trial found that a 6-month intervention did not increase risk or add to symptoms of lymphedema (Ahmed et al., 2006). Other data also indicate that exercise as an individual therapy is neither a contraindication after breast cancer treatment nor does it decrease the risk of developing lymphedema (Ahmed et al., 2006; Schmitz et al., 2009; Johansson et al., 2005). For survivors with lymphedema, compression garments or compression bandages must be worn during exercise to counterbalance the buildup of interstitial fluid (Schmitz et al., 2009; Johansson et al., 2005).

#### **4.4 Surgery**

Surgical approaches are performed to debulk tissue or to divert lymphatic drainage (Casley-Smith, 1992; Cormier et al., 2011). Surgical treatment for breast cancer-related lymphedema is rarely performed except in severe and refractory cases to reduce the weight of the lymphedematous region, minimize the frequency of infectious and inflammatory episodes, and improve cosmesis and function. Surgical treatment includes: (1) excisional operations (e.g., debulking, amputation, and liposuction), (2) lymphatic reconstruction, and (3) tissue transfer procedures (e.g., lymph node transplantation, pedicled omentum, bone marrow stromal cell transplantation) (Cormier et al., 2011). For severe lymphedema, excisional operations and debulking procedures have been reported as effective methods to alleviate symptoms by removing fibrosclerotic connective tissue, excess adipose tissue, and excess skin. Various microsurgical techniques for lymphatic reconstruction have been attempted since the early 1960s, including the creation of anastomoses between lymphatic channels and adjacent veins, between lymph nodes and veins, and between distal and proximal lymphatics (Campisi et al., 2001; O'Brien et al., 1990). Lympho-lymphatic anastomosis and

Preparing for and Coping with Breast Cancer-Related Lymphedema 65

While lymphedema and symptoms have been reported less frequently in women who underwent SLNB only, lymphedema has by no means becomes a minor or disappearing problem. Data from recent studies have revealed that lymphedema remains a significant complication of breast cancer treatment, occurring in 20% to 47% of cases after ALND and in 3% to 17% after SLNB (Cormier et al., 2009; Paskett et al., 2007; Langer et al., 2007; McLaughlin et al., 2008). It is very important to note that surgical removal of lymph nodes remains the optimal choice for treating breast cancer with positive cancerous lymph nodes (Boneti et al., 2008; Giuliano et al, 2011, Langer et al., 2007). Each year in the US, more than 190,000 women are diagnosed with invasive breast cancer and many of them undergo removal of positive lymph nodes despite the use of SLNB, predisposing the women to a life-

In addition, radiation exposure is associated with trauma to the lymphatic system, and current standard of care includes BCS and SLNB together with radiation therapy to breast and /or axilla. Recent innovative approaches to radiotherapy include the single-day targeted intraoperative radiotherapy delivered by the Targit machine (Enderling, Anderson, Chaplain, Munro, & Vaidya, 2006; Vaidya et al., 2006) and the 5-day accelerated partial breast irradiation using a MammoSite catheter (Benitez, et al. 2006; Berlin, Gjores, Ivarsson, Palmqvist, Thagg, & Thulesius, 1999; Borg et al., 2007; Dragun, Harper, Jenrette, Sinha, & Cole, 2007; Jeruss et al., 2006). Such novel radiotherapies targeting directly on the tumor site while avoiding scattering radiation to the axilla may have a role in reducing the risk of lymphedema in comparison to conventional radiotherapy. Research is needed to evaluate targeted radiotherapies in relation to lymphedema risk reduction. As a result, current surgical approaches for diagnosis of and treatment for breast cancer continue to make patients susceptible to the risk of

Besides unavoidable risk factors, such as breast surgery (mastectomy & lumpectomy), removal of lymph nodes (axillary lymph node dissection and sentinel lymph biopsy), presence of positive nodes, radiation and chemotherapy (Mak et al., 2008; Paskett et al., 2007), risk factors that can be managed or avoided are also identified, including obesity, weight gain after cancer treatment, minor upper extremity infections, injury or trauma to the affected side, overuse of the limb, and air travel (Johansson et al., 2002; Mak et al., 2008). Patient education is vital for implementing risk reduction behaviors targeting on such personal risk and triggering factors. In practice, many women treated for breast cancer have not received any information about lymphedema and risk reduction strategies (Fu et al.,

In a recent research on the effectiveness of lymphedema information provision among 136 breast cancer survivors (Fu et al., 2008; Fu et al., 2010), the researchers revealed that 43% percent of the participants reported that they did not receive any lymphedema information. Significantly fewer women who received lymphedema information reported swelling, heaviness, impaired shoulder mobility, seroma formation, and breast swelling. Regarding the most distressing symptom of arm swelling, 41% of patients who did not receive information reported arm swelling, comparing to 19% of those who received information. In terms of important cardinal symptoms of lymphedema, patients who did not receive information also reported significantly more symptoms of heaviness (27%), impaired shoulder mobility (32%), seroma formation (34%), breast swelling (32%),

time risk for lymphedema.

lymphedema.

2010; Ridner, 2006).

lymphatic grafting have been used as reconstructive techniques that are associated with improved patency over time (Brennan & Miller, 1998). A recent systematic review on surgical treatment for lymphedema revealed that the largest reported reductions were noted after excisional procedures (91.1%), lymphatic reconstruction (54.9%), and tissue transfer procedures (47.6%) (Cormier et al., 2011). Potential complications may occur with surgical management of lymphedema, such as recurrence of swelling, poor wound healing, and infection; thus surgical treatment should be considered only when other treatments fail, and with careful consideration of the benefits-to-risks ratio (Casley-Smith, 1992). It should be noted although these surgical approaches have shown promising results, nearly all the surgical procedures do not obviate the need for continued use of conventional therapies, including compression, for long-term maintenance (Cormier et al., 2011).

#### **4.5 Pharmacological therapy**

Pharmacological interventions to treat lymphedema include antibiotics for treatment of infections, benzopyrones, flavonoids, diuretics, hyaluronidase, pantothenic acid, and selenium (Bruns et al., 2003; Rockson et al., 1998; Olszewski et al., 2000). Although not approved by the US Food and Drug Administration (FDA), *benzopyrones* have drawn most of the attention as a pharmacologic approach to treat lymphedema (Rockson et al., 1998). Benzopyrones are believed to encourage protein breakdown and lead to a subsequent decrease in lymph fluid. One randomized controlled trial of benzopyrones and placebo showed a significant decrease in arm swelling after treatment for several months (Davis, 1998). Loprinzi (1999) conducted a controlled study on the effectiveness of coumarin compared with a placebo, and they concluded that coumarin was not effective for managing breast cancer-related lymphedema due to a high risk of hepatotoxicity. A Cochrane review found that it was not possible to draw conclusions about the effectiveness of benzopyrones in reducing and controlling lymphedema due to the poor quality of existing trials (Badger et al., 2004). Flavonoids, hyaluronidase, pantothenic acid, and selenium have also demonstrated limited efficacy (Olszewski et al., 2000; Bruns et al., 2003). Diuretics are not suitable for breast cancer-related lymphedema, as such medications only serve to increase protein concentrations in the interstitium and encourage increase in swelling, inflammation and fibrosis (Davis, 1998; Thiadens, 1998).

#### **5. Risk reduction for and early detection of breast cancer-related lymphedema**

#### **5.1 Risk reduction**

Breast cancer-related lymphedema is often under-diagnosed and undertreated. The complexity and variability of individual lymphatic system and the unpredictability of risk factors makes it difficult to predict which patients will ultimately develop lymphedema. For decades, to reduce the risk of lymphedema after breast cancer treatment, the focus has been on improving surgical treatment. Such improvements, including sentinel lymph node biopsy (SLNB) in which one to three sentinel lymph nodes are removed, and breastconserving surgery (BCS) in which only the cancerous part of the breast is removed (Armer et al., 2004), have saved patients with node-negative disease from unnecessary axillary lymph node dissection (ALND) and mastectomy (Boneti et al., 2008; Giuliano et al, 2011).

lymphatic grafting have been used as reconstructive techniques that are associated with improved patency over time (Brennan & Miller, 1998). A recent systematic review on surgical treatment for lymphedema revealed that the largest reported reductions were noted after excisional procedures (91.1%), lymphatic reconstruction (54.9%), and tissue transfer procedures (47.6%) (Cormier et al., 2011). Potential complications may occur with surgical management of lymphedema, such as recurrence of swelling, poor wound healing, and infection; thus surgical treatment should be considered only when other treatments fail, and with careful consideration of the benefits-to-risks ratio (Casley-Smith, 1992). It should be noted although these surgical approaches have shown promising results, nearly all the surgical procedures do not obviate the need for continued use of conventional therapies,

Pharmacological interventions to treat lymphedema include antibiotics for treatment of infections, benzopyrones, flavonoids, diuretics, hyaluronidase, pantothenic acid, and selenium (Bruns et al., 2003; Rockson et al., 1998; Olszewski et al., 2000). Although not approved by the US Food and Drug Administration (FDA), *benzopyrones* have drawn most of the attention as a pharmacologic approach to treat lymphedema (Rockson et al., 1998). Benzopyrones are believed to encourage protein breakdown and lead to a subsequent decrease in lymph fluid. One randomized controlled trial of benzopyrones and placebo showed a significant decrease in arm swelling after treatment for several months (Davis, 1998). Loprinzi (1999) conducted a controlled study on the effectiveness of coumarin compared with a placebo, and they concluded that coumarin was not effective for managing breast cancer-related lymphedema due to a high risk of hepatotoxicity. A Cochrane review found that it was not possible to draw conclusions about the effectiveness of benzopyrones in reducing and controlling lymphedema due to the poor quality of existing trials (Badger et al., 2004). Flavonoids, hyaluronidase, pantothenic acid, and selenium have also demonstrated limited efficacy (Olszewski et al., 2000; Bruns et al., 2003). Diuretics are not suitable for breast cancer-related lymphedema, as such medications only serve to increase protein concentrations in the interstitium and encourage increase in swelling, inflammation

including compression, for long-term maintenance (Cormier et al., 2011).

**5. Risk reduction for and early detection of breast cancer-related** 

Breast cancer-related lymphedema is often under-diagnosed and undertreated. The complexity and variability of individual lymphatic system and the unpredictability of risk factors makes it difficult to predict which patients will ultimately develop lymphedema. For decades, to reduce the risk of lymphedema after breast cancer treatment, the focus has been on improving surgical treatment. Such improvements, including sentinel lymph node biopsy (SLNB) in which one to three sentinel lymph nodes are removed, and breastconserving surgery (BCS) in which only the cancerous part of the breast is removed (Armer et al., 2004), have saved patients with node-negative disease from unnecessary axillary lymph node dissection (ALND) and mastectomy (Boneti et al., 2008; Giuliano et al, 2011).

**4.5 Pharmacological therapy** 

and fibrosis (Davis, 1998; Thiadens, 1998).

**lymphedema** 

**5.1 Risk reduction** 

While lymphedema and symptoms have been reported less frequently in women who underwent SLNB only, lymphedema has by no means becomes a minor or disappearing problem. Data from recent studies have revealed that lymphedema remains a significant complication of breast cancer treatment, occurring in 20% to 47% of cases after ALND and in 3% to 17% after SLNB (Cormier et al., 2009; Paskett et al., 2007; Langer et al., 2007; McLaughlin et al., 2008). It is very important to note that surgical removal of lymph nodes remains the optimal choice for treating breast cancer with positive cancerous lymph nodes (Boneti et al., 2008; Giuliano et al, 2011, Langer et al., 2007). Each year in the US, more than 190,000 women are diagnosed with invasive breast cancer and many of them undergo removal of positive lymph nodes despite the use of SLNB, predisposing the women to a lifetime risk for lymphedema.

In addition, radiation exposure is associated with trauma to the lymphatic system, and current standard of care includes BCS and SLNB together with radiation therapy to breast and /or axilla. Recent innovative approaches to radiotherapy include the single-day targeted intraoperative radiotherapy delivered by the Targit machine (Enderling, Anderson, Chaplain, Munro, & Vaidya, 2006; Vaidya et al., 2006) and the 5-day accelerated partial breast irradiation using a MammoSite catheter (Benitez, et al. 2006; Berlin, Gjores, Ivarsson, Palmqvist, Thagg, & Thulesius, 1999; Borg et al., 2007; Dragun, Harper, Jenrette, Sinha, & Cole, 2007; Jeruss et al., 2006). Such novel radiotherapies targeting directly on the tumor site while avoiding scattering radiation to the axilla may have a role in reducing the risk of lymphedema in comparison to conventional radiotherapy. Research is needed to evaluate targeted radiotherapies in relation to lymphedema risk reduction. As a result, current surgical approaches for diagnosis of and treatment for breast cancer continue to make patients susceptible to the risk of lymphedema.

Besides unavoidable risk factors, such as breast surgery (mastectomy & lumpectomy), removal of lymph nodes (axillary lymph node dissection and sentinel lymph biopsy), presence of positive nodes, radiation and chemotherapy (Mak et al., 2008; Paskett et al., 2007), risk factors that can be managed or avoided are also identified, including obesity, weight gain after cancer treatment, minor upper extremity infections, injury or trauma to the affected side, overuse of the limb, and air travel (Johansson et al., 2002; Mak et al., 2008). Patient education is vital for implementing risk reduction behaviors targeting on such personal risk and triggering factors. In practice, many women treated for breast cancer have not received any information about lymphedema and risk reduction strategies (Fu et al., 2010; Ridner, 2006).

In a recent research on the effectiveness of lymphedema information provision among 136 breast cancer survivors (Fu et al., 2008; Fu et al., 2010), the researchers revealed that 43% percent of the participants reported that they did not receive any lymphedema information. Significantly fewer women who received lymphedema information reported swelling, heaviness, impaired shoulder mobility, seroma formation, and breast swelling. Regarding the most distressing symptom of arm swelling, 41% of patients who did not receive information reported arm swelling, comparing to 19% of those who received information. In terms of important cardinal symptoms of lymphedema, patients who did not receive information also reported significantly more symptoms of heaviness (27%), impaired shoulder mobility (32%), seroma formation (34%), breast swelling (32%),

Preparing for and Coping with Breast Cancer-Related Lymphedema 67

copyright by Jane Armer. All rights reserved.

Identify the affected or at-risk limb

work and blood pressure.

**Risk Identification** 

**Risk Reduction** 

lymphedema.

**Early Detection** 

awareness.

*Rationale:* 

Fig. 6. Example of severe lymphedema known as elephantiasis

 Recommend the patient use the *unaffected* side for blood pressure and blood work. If the patient had a bilateral mastectomy, suggest use the lower extremities for blood

*Rationale:* By using the unaffected side or lower extremities for blood draws and blood pressure, the patient will reduce the risk for infection, which lowers the risk of

Use 3 questions to screen patients who might have developed lymphedema without

**?** Have you experienced the feeling of heaviness, firmness, tightness in the affected side?



 Refer patient with early signs of symptoms to the certified lymphedema therapists. Assess the patients for signs and symptoms of infections (redness, tenderness, and

**?** Have you noticed any swelling in the affected hand, arm, breast, or trunk area?

since early intervention can sometimes reverse lymphedema symptoms.

pain). Infection, such as cellulitis, is the major predictor for lymphedema. Table 3. Systematic Assessment Strategies for Lymphedema Risk Reduction

**?** Have you experienced any new discomfort in the affected side?

pain). Administer antibiotics as needed.

Ask the patient about history of cancer treatment

firmness/tightness (42%), numbness (39%), tenderness (54%), aching (36%), and stiffness (44%). In summary, patients who received lymphedema information reported significantly fewer symptoms than those who did not (t=3.03; p=0.00). With regard to risk reduction behaviors, patients who received information reported practicing significantly more risk reduction behaviors than those who did not (t=2.42, p=0.01). These behaviors included avoiding blood pressure, blood draws, and injections routinely done in the affected limb, wearing compression garments during air travel, treating minor injuries by washing and applying antibiotics, and most importantly, promoting lymph fluid drainage. In terms of cognitive outcome, patients who received information scored significantly higher in the knowledge test (t=0.49; p=0.00). The researchers developed a multiple regression model to assess the effects of provision of information on lymphedema related symptoms by taking into consideration of treatment-related risk factors. The results demonstrated that provision of information had significant reverse effect (**B**= -1.35; p<0.00) on lymphedema symptoms even taking into consideration of treatment-related risk factors. Together, provision of information and treatment-related risk factors account for 13% of variance (R2= 0.13). After controlling for confounding factors, patient education remains an important predictor of lymphedema outcome.

Apparently, patient education is essential to promote risk reduction and early detection. In clinical practice, healthcare professionals could consider taking the initiative to provide adequate and accurate information and engage patients in supportive dialogues concerning lymphedema and risk reduction to improve patients' cognitive, behavior, and symptom outcomes. Healthcare professionals should equip themselves with lymphedema knowledge, including risk identification, early detection, and risk reduction strategies. Pretreatment education should focus on potential risk for lymphedema, brief review of the lymphatic system and pathophysiology of lymphedema, signs and symptoms of lymphedema, and risk reduction behaviors to reduce the risk from personal and triggering factors. Patients should be educated about the need to seek for professional help immediately if they begin to experience feelings of heaviness or tightness in at‐risk limbs; or if they notice swelling in the affected area; or if the arm and/or at risk chest or truncal areas becomes hot or red. In the clinical settings, healthcare professionals could use the systematic assessment strategies to help patients to reduce the risk of lymphedema presented in Table 3.

#### **5.2 Early detection**

If undiagnosed or not treated effectively, lymphedema can progress into later stages of the condition resulting in a severe form of swelling known as elephantiasis (Figure 5). Early detection of lymphedema is believed to yield better patient outcomes to reduce the risk of the severe stage of lymphedema. To promote early detection, ongoing education should be conducted at each follow-up visit by reviewing the content of pretreatment education and encouraging the patient to report any signs and symptoms of lymphedema such as swelling, tightness, firmness, heaviness, aching, redness, rash, or increased temperature on the affected limb. As certain symptoms, such as tightness, and heaviness are associated with the onset of lymphedema (Armer et al., 2003; Cormier et al., 2009), it is important for healthcare providers to conduct a screening symptom assessment and refer breast cancer survivors with lymphedema to appropriate resources such as lymphedema therapy. (Table 3)

copyright by Jane Armer. All rights reserved.

Fig. 6. Example of severe lymphedema known as elephantiasis

#### **Risk Identification**

66 Novel Strategies in Lymphedema

firmness/tightness (42%), numbness (39%), tenderness (54%), aching (36%), and stiffness (44%). In summary, patients who received lymphedema information reported significantly fewer symptoms than those who did not (t=3.03; p=0.00). With regard to risk reduction behaviors, patients who received information reported practicing significantly more risk reduction behaviors than those who did not (t=2.42, p=0.01). These behaviors included avoiding blood pressure, blood draws, and injections routinely done in the affected limb, wearing compression garments during air travel, treating minor injuries by washing and applying antibiotics, and most importantly, promoting lymph fluid drainage. In terms of cognitive outcome, patients who received information scored significantly higher in the knowledge test (t=0.49; p=0.00). The researchers developed a multiple regression model to assess the effects of provision of information on lymphedema related symptoms by taking into consideration of treatment-related risk factors. The results demonstrated that provision of information had significant reverse effect (**B**= -1.35; p<0.00) on lymphedema symptoms even taking into consideration of treatment-related risk factors. Together, provision of information and treatment-related risk factors account for 13% of variance (R2= 0.13). After controlling for confounding factors, patient education remains an important predictor of lymphedema outcome.

Apparently, patient education is essential to promote risk reduction and early detection. In clinical practice, healthcare professionals could consider taking the initiative to provide adequate and accurate information and engage patients in supportive dialogues concerning lymphedema and risk reduction to improve patients' cognitive, behavior, and symptom outcomes. Healthcare professionals should equip themselves with lymphedema knowledge, including risk identification, early detection, and risk reduction strategies. Pretreatment education should focus on potential risk for lymphedema, brief review of the lymphatic system and pathophysiology of lymphedema, signs and symptoms of lymphedema, and risk reduction behaviors to reduce the risk from personal and triggering factors. Patients should be educated about the need to seek for professional help immediately if they begin to experience feelings of heaviness or tightness in at‐risk limbs; or if they notice swelling in the affected area; or if the arm and/or at risk chest or truncal areas becomes hot or red. In the clinical settings, healthcare professionals could use the systematic assessment strategies to help patients to reduce the risk of

If undiagnosed or not treated effectively, lymphedema can progress into later stages of the condition resulting in a severe form of swelling known as elephantiasis (Figure 5). Early detection of lymphedema is believed to yield better patient outcomes to reduce the risk of the severe stage of lymphedema. To promote early detection, ongoing education should be conducted at each follow-up visit by reviewing the content of pretreatment education and encouraging the patient to report any signs and symptoms of lymphedema such as swelling, tightness, firmness, heaviness, aching, redness, rash, or increased temperature on the affected limb. As certain symptoms, such as tightness, and heaviness are associated with the onset of lymphedema (Armer et al., 2003; Cormier et al., 2009), it is important for healthcare providers to conduct a screening symptom assessment and refer breast cancer survivors

with lymphedema to appropriate resources such as lymphedema therapy. (Table 3)

lymphedema presented in Table 3.

**5.2 Early detection** 


#### **Risk Reduction**


*Rationale:* By using the unaffected side or lower extremities for blood draws and blood pressure, the patient will reduce the risk for infection, which lowers the risk of lymphedema.

#### **Early Detection**


*Rationale:* 


Table 3. Systematic Assessment Strategies for Lymphedema Risk Reduction

Preparing for and Coping with Breast Cancer-Related Lymphedema 69

about developing lymphedema, healthcare professionals should consider asking the survivors if anyone has talked to them about lymphedema risk reduction practices, and if they are concerned about possibly developing lymphedema. For those with lymphedema, healthcare professionals may wish to ask about any problems they are having with swelling, skin integrity, or other problems or concerns they want to discuss related to their lymphedema. These activities, if done in any clinical setting, would begin to address the feelings of abandonment by healthcare professionals verbalized by many breast cancer survivors with lymphedema (Carter, 1997). Management of psychological distress and fatigue associated with lymphedema and self-management may require supportive services from healthcare professionals such as psychologists or conditioning experts (Fu, 2005;

Similar to the self-management for other chronic illnesses, healthcare professionals have a significant role in ensuring effective self-management of lymphedema by motivating breast cancer survivors. Some cognitive, psychological, and social strategies can help breast cancer survivors to promote and maintain self-management behaviors (Fu, 2004). Cognitive strategies refer to breast cancer survivors' ability to understand the need for change of behaviors to implement daily self-management activities and ability to identify and overcome barriers in carrying out such activities. Patient education is the optimal way to

Psychological strategies include those that help breast cancer survivors set goals for their lymphedema management and motivate them to continue their daily management activities. Fu (2005) identifies four major intentions undertaken by breast cancer survivors to promote effective daily lymphedema management: keeping in mind the consequences, preventing lymphedema from getting worse, getting ready to live with lymphedema, and integrating the care of lymphedema into daily life. The four intentions reveal in detail the way in which breast cancer survivors structure their lives to manage lymphedema daily. Healthcare professionals are in the best position to identify breast cancer survivors' individual needs by assessing the presence or absence of the intentions. In another recent study (Fu, 2010), the researcher described how breast cancer survivors actively and creatively structured their lives to make lymphedema self-management feasible by making conscious decisions about new-fangled limitations, making daily care feasible, and incorporating lymphedema care into daily routine. The study also identified effective and ineffective strategies and barriers to fulfill the intentions of self management (Table 4). Research is needed to develop interventions to test the identified effective strategies for self-

Social strategies focus on providing resources or support groups to externally enhance breast cancer survivors' motivation to continue self-management to maintain LV and deal with physical symptoms as well as psychological distress and social anxiety. Internal and external resources, such as programs about lymphedema treatment and reliable internet websites, should be given to breast cancer survivors. Providing social support helps mitigate breast cancer survivors' sense of being singled-out, a perspective that was vividly described by a breast cancer survivors with five years of lymphedema, "You feel that you are on this little island by yourself and just struggling because there is no one else around who knows what lymphedema is" (Fu, 2003, p. 188). Support group in which women can feel free to share their success stories about lymphedema management and the ways of overcoming

enhance breast cancer survivors' knowledge and provide relevant resources.

Ridner, 2005).

management of lymphedema.

To promote early intervention, it is imperative to implement screening and measurement for early detection of breast cancer-related lymphedema. In a prospective observational study on 196 women with newly diagnosed breast cancer over a five year period (Stout et al., 2008), the women were measured using *infra-red Perometry* prior to their surgery and in three-month intervals following their surgery for up to one year. During that time, researchers were able to identify the development of subclinical lymphedema in 43 women (22%). The women with subclinical lymphedema (defined by the researchers as the limb volume change [LVC] of approximately 100 ml or a 3% LVC compared to the pre-op measure) were treated with an off-the- shelf sleeve and gauntlet, which was worn daily except during sleeping hours. Significant reduction in limb volume was observed that was similar to nearly the women's pre-surgical baseline value in all patients over an average period of 4.4 weeks. It should be noted that pre‐treatment baseline measurement of limbs is essential, as this serves as the baseline data to which subsequent measurements can be compared. Healthcare professionals should use a cost-effective measuring method (such as circumferential arm measurement) and a time- and energy-saving measuring method (such as infra-red perometry) to monitor LVC in breast cancer survivors. Limb volume measurement should be conducted by the healthcare professionals who treat breast cancer and follow breast cancer survivors at each patient visit. In this way, patients with increased LV in the affected limb can be referred in a timely manner for further assessment and early intervention by specialists in lymphedema treatment.

#### **6. Self-management for breast cancer-related lymphedema**

Self-management for breast cancer-related lymphedema focuses on daily activities and strategies undertaken by breast cancer survivors to decrease the swelling, relieve symptoms, and prevent acute exacerbations and infections (Fu, 2005). As discussed previously, CDT requires patients to make a daily commitment by using external compression (sleeve, glove, wrap, bandage, or pump), performing remedial exercise, self-MLD and skin care (Davis, 1998; Rockson, et al. 1998). Self-management is essential for the success of the maintenance phase of the complete decongestive therapy (CDT) (Fu, 2010). Successful self-management of lymphedema also requires breast cancer survivors to initiate and maintain behaviors reduce triggering factors that can lead to severe lymphedema (Fu, 2005).

Limited research has been conducted on effective self-management of lymphedema. Very few exiting research are descriptive in nature yet the studies have delineated the difficulties and barriers that impede the effective self-management of lymphedema. A recent study revealed the major barriers to effective daily self-management include fatigue, lack of sufficient supporting system, insufficient financial resources, insufficient time, occupations involving manual laborious work, employers' misunderstanding, unsupportive working environment, fear of losing job (or stigma, embarrassment or discrimination), irregular working schedules, lack of clear or detailed instructions for self-care, lack of experience of organizing or following a schedule, and lack of experience of establishing or maintaining a routine (Fu, 2010). Currently, no research has been targeting on the identified barriers to promote self-management.

Breast cancer-related lymphedema is a chronic disease that, unlike other chronic illnesses such as arthritis or diabetes, receives little attention from healthcare professionals in clinical settings. To provide an emotional outlet for breast cancer survivors who may be concerned

To promote early intervention, it is imperative to implement screening and measurement for early detection of breast cancer-related lymphedema. In a prospective observational study on 196 women with newly diagnosed breast cancer over a five year period (Stout et al., 2008), the women were measured using *infra-red Perometry* prior to their surgery and in three-month intervals following their surgery for up to one year. During that time, researchers were able to identify the development of subclinical lymphedema in 43 women (22%). The women with subclinical lymphedema (defined by the researchers as the limb volume change [LVC] of approximately 100 ml or a 3% LVC compared to the pre-op measure) were treated with an off-the- shelf sleeve and gauntlet, which was worn daily except during sleeping hours. Significant reduction in limb volume was observed that was similar to nearly the women's pre-surgical baseline value in all patients over an average period of 4.4 weeks. It should be noted that pre‐treatment baseline measurement of limbs is essential, as this serves as the baseline data to which subsequent measurements can be compared. Healthcare professionals should use a cost-effective measuring method (such as circumferential arm measurement) and a time- and energy-saving measuring method (such as infra-red perometry) to monitor LVC in breast cancer survivors. Limb volume measurement should be conducted by the healthcare professionals who treat breast cancer and follow breast cancer survivors at each patient visit. In this way, patients with increased LV in the affected limb can be referred in a timely manner for further assessment and early

intervention by specialists in lymphedema treatment.

promote self-management.

**6. Self-management for breast cancer-related lymphedema** 

reduce triggering factors that can lead to severe lymphedema (Fu, 2005).

Self-management for breast cancer-related lymphedema focuses on daily activities and strategies undertaken by breast cancer survivors to decrease the swelling, relieve symptoms, and prevent acute exacerbations and infections (Fu, 2005). As discussed previously, CDT requires patients to make a daily commitment by using external compression (sleeve, glove, wrap, bandage, or pump), performing remedial exercise, self-MLD and skin care (Davis, 1998; Rockson, et al. 1998). Self-management is essential for the success of the maintenance phase of the complete decongestive therapy (CDT) (Fu, 2010). Successful self-management of lymphedema also requires breast cancer survivors to initiate and maintain behaviors

Limited research has been conducted on effective self-management of lymphedema. Very few exiting research are descriptive in nature yet the studies have delineated the difficulties and barriers that impede the effective self-management of lymphedema. A recent study revealed the major barriers to effective daily self-management include fatigue, lack of sufficient supporting system, insufficient financial resources, insufficient time, occupations involving manual laborious work, employers' misunderstanding, unsupportive working environment, fear of losing job (or stigma, embarrassment or discrimination), irregular working schedules, lack of clear or detailed instructions for self-care, lack of experience of organizing or following a schedule, and lack of experience of establishing or maintaining a routine (Fu, 2010). Currently, no research has been targeting on the identified barriers to

Breast cancer-related lymphedema is a chronic disease that, unlike other chronic illnesses such as arthritis or diabetes, receives little attention from healthcare professionals in clinical settings. To provide an emotional outlet for breast cancer survivors who may be concerned about developing lymphedema, healthcare professionals should consider asking the survivors if anyone has talked to them about lymphedema risk reduction practices, and if they are concerned about possibly developing lymphedema. For those with lymphedema, healthcare professionals may wish to ask about any problems they are having with swelling, skin integrity, or other problems or concerns they want to discuss related to their lymphedema. These activities, if done in any clinical setting, would begin to address the feelings of abandonment by healthcare professionals verbalized by many breast cancer survivors with lymphedema (Carter, 1997). Management of psychological distress and fatigue associated with lymphedema and self-management may require supportive services from healthcare professionals such as psychologists or conditioning experts (Fu, 2005; Ridner, 2005).

Similar to the self-management for other chronic illnesses, healthcare professionals have a significant role in ensuring effective self-management of lymphedema by motivating breast cancer survivors. Some cognitive, psychological, and social strategies can help breast cancer survivors to promote and maintain self-management behaviors (Fu, 2004). Cognitive strategies refer to breast cancer survivors' ability to understand the need for change of behaviors to implement daily self-management activities and ability to identify and overcome barriers in carrying out such activities. Patient education is the optimal way to enhance breast cancer survivors' knowledge and provide relevant resources.

Psychological strategies include those that help breast cancer survivors set goals for their lymphedema management and motivate them to continue their daily management activities. Fu (2005) identifies four major intentions undertaken by breast cancer survivors to promote effective daily lymphedema management: keeping in mind the consequences, preventing lymphedema from getting worse, getting ready to live with lymphedema, and integrating the care of lymphedema into daily life. The four intentions reveal in detail the way in which breast cancer survivors structure their lives to manage lymphedema daily. Healthcare professionals are in the best position to identify breast cancer survivors' individual needs by assessing the presence or absence of the intentions. In another recent study (Fu, 2010), the researcher described how breast cancer survivors actively and creatively structured their lives to make lymphedema self-management feasible by making conscious decisions about new-fangled limitations, making daily care feasible, and incorporating lymphedema care into daily routine. The study also identified effective and ineffective strategies and barriers to fulfill the intentions of self management (Table 4). Research is needed to develop interventions to test the identified effective strategies for selfmanagement of lymphedema.

Social strategies focus on providing resources or support groups to externally enhance breast cancer survivors' motivation to continue self-management to maintain LV and deal with physical symptoms as well as psychological distress and social anxiety. Internal and external resources, such as programs about lymphedema treatment and reliable internet websites, should be given to breast cancer survivors. Providing social support helps mitigate breast cancer survivors' sense of being singled-out, a perspective that was vividly described by a breast cancer survivors with five years of lymphedema, "You feel that you are on this little island by yourself and just struggling because there is no one else around who knows what lymphedema is" (Fu, 2003, p. 188). Support group in which women can feel free to share their success stories about lymphedema management and the ways of overcoming

Preparing for and Coping with Breast Cancer-Related Lymphedema 71

barriers is an effective way to provide social support (Fu, 2005). Well-designed support groups can also enhance skills for effective lymphedema management through group practice of certain skills such as easier ways of putting on a compression garment, applying bandage or wraps, and performing self-MLD. Group practice allows the opportunity not only for building a community to further promote breast cancer survivors' sense of belongingness, but also for transforming routine lymphedema management activities into fun activities that may elicit interest and enjoyment to sustain the women's motivation. The lifetime commitment to manage lymphedema requires time and effort by both breast cancer survivors and healthcare professionals to insure that quality life is not profoundly impacted.

It has been well documented that psychological health can be impacted by changes in physical appearance and limitations created by lymphedema (e.g., Petrek et al., 2001; Radina & Armer, 2001, 2004; Thomas-MacLean et al., 2005). This includes both mental health concerns and the ways in which patients cope with the physical limitations brought on my

In addition to the physical limitations of breast cancer-related lymphedema, patients are also subject to potential psychosocial problems including depression, anxiety, poor adjustment to illness, and low self esteem (Maunsell, Brisson, & Deschenes, 1993; Thomas-MacLean et al., 2005). Chachaj and collegues (2010) found that there were several factors that contributed to patients' experiences of negative psychosocial outcomes. These included "pain in the upper limb (mainly shoulder and arm), pain in operated breast, difficulties with arm movement, localization of lymphedema within the hand or in operated breast, a history of dermatolymphangitis and of receiving chemotherapy"(p. Vassard and colleagues (2010) explored the psychosocial outcomes of patients engaged in post-breast cancer surgery rehabilitation. They found that compared with patients who did not develop lymphedema, those with lymphedema reported a greater impact on their psychological well-being. Specifically, patients with breast cancer-related lymphedema were more likely to report lower overall quality of life and perceiving themselves to be in poorer health. These findings are similar to those reported by Heiney and colleagues (2007) who found that both physical and social aspects of quality of life were impacted by breast cancer-related lymphedema. Researchers have also found that the degree to which patients experience negative impacts on their mental health and quality of life is correlated with the severity of the lymphedema symptoms and the degree to which these symptoms are viewed as distressful (Erickson et al., 2001; Kornblith, Herndon, Weiss, Zhang, Zuckerman, Rosenberg et al., 2003). Similarly, Ridner (2005) found that patients with breast cancer-related lymphedema reported higher levels of emotional distress and reduced body confidence then those without lymphedema. Certainly this finding of reduced body confidence has implications for patients' self-esteem as well as sexual intimacy. With regard to addressing psychosocial problems in this population, Hamilton, Miedema, MacIntyre, & Easley, 2011) investigated the use of a positive self-talk intervention. Their findings suggest that such interventions may have a positive impact on patients' coping skills. They argue that further investigations are needed

**7. Strategies for personal and family-level care** 

breast cancer-related lymphedema in their daily lives.

**7.1 Individual-level psychosocial impacts** 

**7.1.1 Mental health concerns** 


Table 4. Intentions, Effective strategies, Barriers and Ineffective Strategies (Adapted from: Fu, M.R. (2010). Cancer Survivors' views of lymphoedema management. *Journal of Lymphoedema, 5*(2), 39-48.)

barriers is an effective way to provide social support (Fu, 2005). Well-designed support groups can also enhance skills for effective lymphedema management through group practice of certain skills such as easier ways of putting on a compression garment, applying bandage or wraps, and performing self-MLD. Group practice allows the opportunity not only for building a community to further promote breast cancer survivors' sense of belongingness, but also for transforming routine lymphedema management activities into fun activities that may elicit interest and enjoyment to sustain the women's motivation. The lifetime commitment to manage lymphedema requires time and effort by both breast cancer survivors and healthcare professionals to insure that quality life is not profoundly impacted.

#### **7. Strategies for personal and family-level care**

#### **7.1 Individual-level psychosocial impacts**

It has been well documented that psychological health can be impacted by changes in physical appearance and limitations created by lymphedema (e.g., Petrek et al., 2001; Radina & Armer, 2001, 2004; Thomas-MacLean et al., 2005). This includes both mental health concerns and the ways in which patients cope with the physical limitations brought on my breast cancer-related lymphedema in their daily lives.

#### **7.1.1 Mental health concerns**

70 Novel Strategies in Lymphedema

**Making Self Management Feasible Intentions Effective Strategies Barriers to the strategy Ineffective** 

> Lack of sufficient supporting system of family, friends, and coworkers Unsupportive working environment Employers'

misunderstanding Insufficient financial resources

 Occupations involving manual laborious work

 Lack of clear or detailed instructions Insufficient time Insufficient financial resources Insufficient qualified therapists Fatigue

 Fear of losing job, stigma, embarrassment or discrimination Occupations involving manual laborious work

Employers'

misunderstanding Unsupportive working environment Lack of sufficient supporting system

 Lack of experience of organizing or following a

Irregular working schedules

 Being a good wife and loving mother

schedule Lack of experience of establishing or maintaining

a routine Insufficient time

Fatigue

Table 4. Intentions, Effective strategies, Barriers and Ineffective Strategies (Adapted from: Fu, M.R. (2010). Cancer Survivors' views of lymphoedema management. *Journal of* 

Impatience

**Making Conscious Decisions about New-fangled Limitations** 

**Making daily Care** 

**Feasible** 

**Incorporating Lymphedema Care into Daily Routine** 

*Lymphoedema, 5*(2), 39-48.)

 Giving up Letting go Asking for help Paying for help

Using the unaffected limb

compressive garments as much as possible Using *Easy Slide* or other device to help putting on the compression sleeve Wrapping the affected arm during nighttime Using rubber gloves to protect the compression gloves from getting dirty Performing exercise and massage if time and physical stamina allow Getting an easy access to the things needed for lymphedema care Spacing out the household chores Having someone help Wearing protective gloves for dish washing, cleaning, and gardening Using food processor to

Wearing daytime

cut food

life

Establishing and

 Readjusting to the established routine

sustaining a daily routine Foreseeing the changes in **Strategies** 

 Ignoring Forgetting Neglecting

 Trying to do all that you were told

 Following an irregular schedule

In addition to the physical limitations of breast cancer-related lymphedema, patients are also subject to potential psychosocial problems including depression, anxiety, poor adjustment to illness, and low self esteem (Maunsell, Brisson, & Deschenes, 1993; Thomas-MacLean et al., 2005). Chachaj and collegues (2010) found that there were several factors that contributed to patients' experiences of negative psychosocial outcomes. These included "pain in the upper limb (mainly shoulder and arm), pain in operated breast, difficulties with arm movement, localization of lymphedema within the hand or in operated breast, a history of dermatolymphangitis and of receiving chemotherapy"(p. Vassard and colleagues (2010) explored the psychosocial outcomes of patients engaged in post-breast cancer surgery rehabilitation. They found that compared with patients who did not develop lymphedema, those with lymphedema reported a greater impact on their psychological well-being. Specifically, patients with breast cancer-related lymphedema were more likely to report lower overall quality of life and perceiving themselves to be in poorer health. These findings are similar to those reported by Heiney and colleagues (2007) who found that both physical and social aspects of quality of life were impacted by breast cancer-related lymphedema. Researchers have also found that the degree to which patients experience negative impacts on their mental health and quality of life is correlated with the severity of the lymphedema symptoms and the degree to which these symptoms are viewed as distressful (Erickson et al., 2001; Kornblith, Herndon, Weiss, Zhang, Zuckerman, Rosenberg et al., 2003). Similarly, Ridner (2005) found that patients with breast cancer-related lymphedema reported higher levels of emotional distress and reduced body confidence then those without lymphedema. Certainly this finding of reduced body confidence has implications for patients' self-esteem as well as sexual intimacy. With regard to addressing psychosocial problems in this population, Hamilton, Miedema, MacIntyre, & Easley, 2011) investigated the use of a positive self-talk intervention. Their findings suggest that such interventions may have a positive impact on patients' coping skills. They argue that further investigations are needed

Preparing for and Coping with Breast Cancer-Related Lymphedema 73

Ziebland, & Stein, 2009; Mallinger et al., 2006), and the family's role as either a supportive or distressing unit (Alfano & Roland, 2006; Spencer et al., 1999). Here we review the research that has been conducted that investigates the specific ways in which breast cancer patients with lymphedema experience their family and interpersonal lives with regard to family work, family play, and sexual intimacy with significant romantic others. We conclude by exploring a theory of health-related family quality of life and how it might be applied to

The daily lives and rhythms of families include both getting the work of the family completed (i.e., housework) and the maintenance of family relationships (i.e., spending quality time together). Researchers have shown that both aspects of family functioning can be impacted by the onset and continued care required of breast cancer-related lymphedema (Radina, 2009; Radina & Armer 2001; 2004). That is, the physical limitations and psychosocial difficulties experienced by women with lymphedema frequently require the individual and her family members to renegotiate family roles and modify how they function as a unit (Radina & Armer, 2001; 2004). With regard to family work, this may include a redistribution of household responsibilities (i.e., asking an adult son to run the vacuum or employing a maid service to do the heavy cleaning) or the modification of how and if such responsibilities are undertaken (i.e., lowering standards of household cleanliness, learning to use the other arm to sweep the kitchen floor) (Radina & Armer, 2001). Women at-risk for developing breast cancer-related lymphedema have been shown to struggle with balancing the needs of others (e.g., family members) with their own needs for self-care that are aimed at reducing their risk of developing or exacerbating breast cancer-related lymphedema (Radina, Armer, & Stewart, under review). Gilligan and others (e.g., Jack, 1991; Ruddick, 1989) have argued that women are socialized within family and community life to embrace this concept of self-sacrifice in the service of others. Caring for others, and doing so in an unselfish way or at the expense of one's own needs, is the currency that women are socialized to deal with in order to create and maintain relationships with others (Jack, 1991). The role women often assume in family life requires some degree of self-sacrifice in order to manage the household and take care of family members (Mederer, 1993), including paid work outside the home. In this sense, what gets put on hold are activities like personal care, medication, exercise, or other activities that are largely for the benefit of the woman alone and not explicitly benefiting the family as a whole or individual family members. Radina and colleagues (under review) found that women at-risk for developing breast cancer-related lymphedema struggled with making their self-care a priority despite being enrolled in an intervention study aimed at teaching them techniques for self-care to reduce their risk of developing breast cancer-related lymphedema. Often the major barrier to self-care was the pull they felt to put others' needs first. Consistent with Ridner, Dietrich, and Kidd (2011) of women diagnosed with lymphedema, Radina et al. (under review) found that these women at-risk for developing lymphedema struggled with finding the time in their daily lives to engage in self-care. Radina and colleagues' findings highlight the important role that social contexts (e.g., family life, gendered expectations) can play as a factor in personal care for breast cancer

families coping with breast cancer-related lymphedema.

**7.2.1 Family work and family play** 

survivors.

to determine appropriate psychological interventions that positively impact such mental health concerns as anxiety and depression among patients with breast cancer-related lymphedema.

#### **7.1.2 Coping with physical limitations in daily life**

Lymphedema can impose limitations on women's lives in terms of their ability to participate in normal, daily activities (Radina & Armer, 2001; Ridner, 2002). Radina (2009) found that women with breast cancer-related lymphedema experienced a heightened sense of awareness and caution concerning their physical activities, as well as a sense of frustration with the limitations they faced as a result of breast cancer-related lymphedema. At the same time, these women also must engage in time consuming self-care, as described above, in order to reduce and control the swelling associated with lymphedema (e.g., manual lymph draining, CDT). Not only are some of these treatments restricting in terms of range of motion, but they also require the patient to set aside time during the day to perform them and to potentially ask others (i.e., family members) for help. The patient must also avoid getting any wrappings wet and therefore must remove the wrapping and rewrap the arm for bathing or other water activities (e.g., swimming, washing dishes). Lastly, because the compression sleeve is so expensive and must be washed by hand everyday, the patient must be careful not to stain or otherwise damage the sleeve (Casley-Smith, 1992).

#### **7.2 Family/interpersonal relationship-level psychosocial impacts**

Given the increasing large population of women living as breast cancer survivors and the understanding that breast cancer impacts the entire family, not just the patient/survivor (Baider, Cooper, & Kaplan De-Nour, 2000; Veach, Nicholas, & Barton, 2002), a growing number of families may be facing the need to navigate survivorship as well. At the same time, given that as many as 40% of women who have gone through breast cancer treatment may develop breast-cancer related lymphedema, there is also a growing number of families who are not only needing to cope with cancer survivorship in general but also coping daily with the chronic condition of lymphedema.

The study of breast cancer survivorship in general has largely centered on the experiences of breast cancer patients and has failed to sufficiently consider the impact that breast cancer diagnosis and treatment can have on family members and family life. The majority of work that considers family members is focused on breast cancer patients' relationships with husbands and young children (e.g., Northouse, Laten, & Reddy, 1995; Radina, 2009; Radina & Armer, 2001; 2004, Radina, Watson, & Faubert, 2009; Rees & Bath, 2000) and the individual quality of life of patients and their family members in the context of breast cancer (e.g., Kim & Given, 2008; Northouse et al., 2002). Only recently have researchers focused attention on how family functioning and adaptation can influence the lives of breast cancer patients and survivors (e.g., Mallinger, Griggs, & Shields, 2006; Radina, 2009; Radina & Armer, 2001; 2004; Radina et al., 2009). The evolution of empirically based understanding of how cancer in general impacts the family continues to evolve. The limited research that explores family dynamics in the context of breast cancer focuses on issues such as participation in treatment decision making (Lacey, 2002; Raveis & Pretter, 2004), family communication patterns both prior to and after the breast cancer diagnosis (Forest, Plumb, Ziebland, & Stein, 2009; Mallinger et al., 2006), and the family's role as either a supportive or distressing unit (Alfano & Roland, 2006; Spencer et al., 1999). Here we review the research that has been conducted that investigates the specific ways in which breast cancer patients with lymphedema experience their family and interpersonal lives with regard to family work, family play, and sexual intimacy with significant romantic others. We conclude by exploring a theory of health-related family quality of life and how it might be applied to families coping with breast cancer-related lymphedema.

#### **7.2.1 Family work and family play**

72 Novel Strategies in Lymphedema

to determine appropriate psychological interventions that positively impact such mental health concerns as anxiety and depression among patients with breast cancer-related

Lymphedema can impose limitations on women's lives in terms of their ability to participate in normal, daily activities (Radina & Armer, 2001; Ridner, 2002). Radina (2009) found that women with breast cancer-related lymphedema experienced a heightened sense of awareness and caution concerning their physical activities, as well as a sense of frustration with the limitations they faced as a result of breast cancer-related lymphedema. At the same time, these women also must engage in time consuming self-care, as described above, in order to reduce and control the swelling associated with lymphedema (e.g., manual lymph draining, CDT). Not only are some of these treatments restricting in terms of range of motion, but they also require the patient to set aside time during the day to perform them and to potentially ask others (i.e., family members) for help. The patient must also avoid getting any wrappings wet and therefore must remove the wrapping and rewrap the arm for bathing or other water activities (e.g., swimming, washing dishes). Lastly, because the compression sleeve is so expensive and must be washed by hand everyday, the patient must

Given the increasing large population of women living as breast cancer survivors and the understanding that breast cancer impacts the entire family, not just the patient/survivor (Baider, Cooper, & Kaplan De-Nour, 2000; Veach, Nicholas, & Barton, 2002), a growing number of families may be facing the need to navigate survivorship as well. At the same time, given that as many as 40% of women who have gone through breast cancer treatment may develop breast-cancer related lymphedema, there is also a growing number of families who are not only needing to cope with cancer survivorship in general but also coping daily

The study of breast cancer survivorship in general has largely centered on the experiences of breast cancer patients and has failed to sufficiently consider the impact that breast cancer diagnosis and treatment can have on family members and family life. The majority of work that considers family members is focused on breast cancer patients' relationships with husbands and young children (e.g., Northouse, Laten, & Reddy, 1995; Radina, 2009; Radina & Armer, 2001; 2004, Radina, Watson, & Faubert, 2009; Rees & Bath, 2000) and the individual quality of life of patients and their family members in the context of breast cancer (e.g., Kim & Given, 2008; Northouse et al., 2002). Only recently have researchers focused attention on how family functioning and adaptation can influence the lives of breast cancer patients and survivors (e.g., Mallinger, Griggs, & Shields, 2006; Radina, 2009; Radina & Armer, 2001; 2004; Radina et al., 2009). The evolution of empirically based understanding of how cancer in general impacts the family continues to evolve. The limited research that explores family dynamics in the context of breast cancer focuses on issues such as participation in treatment decision making (Lacey, 2002; Raveis & Pretter, 2004), family communication patterns both prior to and after the breast cancer diagnosis (Forest, Plumb,

be careful not to stain or otherwise damage the sleeve (Casley-Smith, 1992).

**7.2 Family/interpersonal relationship-level psychosocial impacts** 

with the chronic condition of lymphedema.

lymphedema.

**7.1.2 Coping with physical limitations in daily life** 

The daily lives and rhythms of families include both getting the work of the family completed (i.e., housework) and the maintenance of family relationships (i.e., spending quality time together). Researchers have shown that both aspects of family functioning can be impacted by the onset and continued care required of breast cancer-related lymphedema (Radina, 2009; Radina & Armer 2001; 2004). That is, the physical limitations and psychosocial difficulties experienced by women with lymphedema frequently require the individual and her family members to renegotiate family roles and modify how they function as a unit (Radina & Armer, 2001; 2004). With regard to family work, this may include a redistribution of household responsibilities (i.e., asking an adult son to run the vacuum or employing a maid service to do the heavy cleaning) or the modification of how and if such responsibilities are undertaken (i.e., lowering standards of household cleanliness, learning to use the other arm to sweep the kitchen floor) (Radina & Armer, 2001). Women at-risk for developing breast cancer-related lymphedema have been shown to struggle with balancing the needs of others (e.g., family members) with their own needs for self-care that are aimed at reducing their risk of developing or exacerbating breast cancer-related lymphedema (Radina, Armer, & Stewart, under review). Gilligan and others (e.g., Jack, 1991; Ruddick, 1989) have argued that women are socialized within family and community life to embrace this concept of self-sacrifice in the service of others. Caring for others, and doing so in an unselfish way or at the expense of one's own needs, is the currency that women are socialized to deal with in order to create and maintain relationships with others (Jack, 1991). The role women often assume in family life requires some degree of self-sacrifice in order to manage the household and take care of family members (Mederer, 1993), including paid work outside the home. In this sense, what gets put on hold are activities like personal care, medication, exercise, or other activities that are largely for the benefit of the woman alone and not explicitly benefiting the family as a whole or individual family members. Radina and colleagues (under review) found that women at-risk for developing breast cancer-related lymphedema struggled with making their self-care a priority despite being enrolled in an intervention study aimed at teaching them techniques for self-care to reduce their risk of developing breast cancer-related lymphedema. Often the major barrier to self-care was the pull they felt to put others' needs first. Consistent with Ridner, Dietrich, and Kidd (2011) of women diagnosed with lymphedema, Radina et al. (under review) found that these women at-risk for developing lymphedema struggled with finding the time in their daily lives to engage in self-care. Radina and colleagues' findings highlight the important role that social contexts (e.g., family life, gendered expectations) can play as a factor in personal care for breast cancer survivors.

Preparing for and Coping with Breast Cancer-Related Lymphedema 75

shared leisure time is associated with enhanced family communication and stability (Guerin & Dattilo, 2001). For individuals with disabilities, the benefits of leisure activities (e.g., increases in self-confidence, social networks, and one's sense of accomplishment and satisfaction) have been well-established (Jo et al., 2004; Lloyd, King, Lampe, & McDougall, 2001). Despite this relationship, families with a disabled member are less likely to participate in balance leisure activities (38%) compared to families without a member with a disability

Radina (2009) found that women with breast cancer-related lymphedema approached their participation in family leisure activities in two ways. The first involved continued participation in family leisure activities but with extra care (e.g., purchasing light weight hiking equipment) or being creative about how they participated (e.g., becoming the scout troop treasurer rather than accompanying children on back packing trips). The second strategy involved withdrawing from family activities that according to the Core and Balance Model (Zabriskie et al., 2001) could jeopardize overall levels of family functioning by eliminating opportunities for building or improving family adaptability, cohesion, or

Sexuality can be examined as an interaction of biological, psychological, and social domains of life (Lindau, Laumann, Levinson, & Waite, 2003; National Institute on Aging, 2005). How individuals feel about themselves as sexual beings is impacted by a combination of all three of these areas. As women with breast cancer-related lymphedema have already faced breast cancer, their feelings about sexuality and intimacy are intertwined with their breast cancer and lymphedema experiences. Thus, it may not be possible to completely distinguish between body image issues, feelings of sexuality, and the impact on sexual relationships

Researchers have explored the impact of breast cancer on sexuality and sexual relationships (e.g., Henson, 2002). This work has included investigations into the impact of breast cancer and its treatment on hormones and sexual functioning, attitudes of a romantic partner, the impact of fatigue brought about by treatment on sexual relationships, and how an altered body image resulting from (breast) cancer can impact one's sexuality and sexual relationships (Gould, Grassau, Manthorne, Gray, & Fitch, 2006). Research also have focused on how there tends to be a lack of information on how breast cancer and its treatment can impact sexuality that is provided to breast cancer patient and their partners (Gould et al.,

With breast cancer-related lymphedema, women may experience changes in their appearance as well as pain and physical limitations due to swelling (Passik & McDonald, 1998). As sexuality is connected to a woman's feelings about herself and her body, not only the experience of breast cancer, but also the development of lymphedema can have a serious impact on her views of herself as sexual and her willingness to be physical with a partner. Having survived breast cancer to now have to contend with breast cancer-related lymphedema can be seen "as a secondary blow to their physical and emotional well-being," which includes their intimate relationships with others (Passik and McDonald, 1998, p. 2818). Research (e.g., Koch et al., 2005; Radina, Watson, & Faubert, 2009; Wiederman &

brought about by breast cancer and those resulting from lymphedema.

(52%; Jo et al., 2004).

communication.

2006; Henson, 2002).

**7.2.2 Sexuality and intimacy** 

Radina (2009) found that for some women with breast cancer-related lymphedema, lifestyle modifications extend beyond daily activities such as dressing, bathing, cooking, and housekeeping into the realm of leisure. When it comes to leisure activities, wives and mothers who are often responsible for family management, are likely to be the ones creating time and space for other family members' independent leisure activities (e.g., backing cupcakes for her son's football team party, driving children to music lessons). Because of these other responsibilities, women's independent leisure is often sacrificed so that they can accomplish these other tasks for their families (Henderson, Bialeschki, Shaw, & Freysinger, 1999).

For women, their own participation in leisure activities in general, whether engaged in individually or with their families, may act as a buffer against stressful life events such as breast cancer and breast cancer-related lymphedema (Pondé & Santana, 2000). Thus, the continued participation of women with lymphedema in leisure activities appears valuable for sustaining their quality of life after breast cancer treatment. At the same time, family leisure is important for understanding family functioning (Zabriski & McCormick, 2001), particularly in the context of chronic health conditions and health-related disabilities (Jo, Kosciulek, Huh, & Holecek, 2004). Radina (2009) found that breast cancer-related lymphedema can create serious limitations that can impact both family functioning and participation in leisure.

Family interaction in the context of leisure enhances the family's ability to remain stable (Orthner & Mancini, 1990). In fact, researchers have demonstrated that there is a positive relationship between family leisure engagement, family satisfaction, and family quality of life (Zabriskie & McCormick, 2003). The Core and Balance Model of Family Leisure Functioning (Zabriskie, 2000; Zabriskie & McCormick, 2001) suggests that family adaptability (i.e., the family's ability to be flexible and change), cohesion (i.e., closeness, emotional bonding), and communication are facilitated through family members' joint engagement in family-based leisure activities (Zabriskie & McCormick, 2001). These can include both core and balance leisure activities. Core leisure activities are "common everyday, low-cost, relatively accessible, and often home-based activities that families do frequently" (Zabriskie & McCormick, 2003, p. 168) including such activities as playing a game, e-mailing or instant messaging with family members, and making/eating dinner together (Zabriskie & McCormick, 2001). Core leisure activities tend to be associated with the maintenance of family cohesion and thus families who perceived themselves as having high levels of emotional closeness report engaging in more core leisure activities (Zabriskie, McCormick, & Austin, 2001). Balance leisure activities are "less common, less frequent, more out of the ordinary, and usually not home based thus providing novel experiences" (Zabriskie & McCormick, 2003, p. 168) including such activities as family travel, family reunions, and special family events (Zabriskie & McCormick, 2001). Balance activities tend to be associated with maintaining family adaptability (Zabriskie et al., 2001). According to the Core and Balance Model, in order to have healthier family functioning that results from increased levels of family communication, families should participate in both core and balance activities that enhance both family cohesion and adaptability (Zabriskie & McCormick, 2003).

The role that family leisure plays generally also applies to families in which there is a chronically ill or disabled member (i.e., lymphedema). For such families participating in shared leisure time is associated with enhanced family communication and stability (Guerin & Dattilo, 2001). For individuals with disabilities, the benefits of leisure activities (e.g., increases in self-confidence, social networks, and one's sense of accomplishment and satisfaction) have been well-established (Jo et al., 2004; Lloyd, King, Lampe, & McDougall, 2001). Despite this relationship, families with a disabled member are less likely to participate in balance leisure activities (38%) compared to families without a member with a disability (52%; Jo et al., 2004).

Radina (2009) found that women with breast cancer-related lymphedema approached their participation in family leisure activities in two ways. The first involved continued participation in family leisure activities but with extra care (e.g., purchasing light weight hiking equipment) or being creative about how they participated (e.g., becoming the scout troop treasurer rather than accompanying children on back packing trips). The second strategy involved withdrawing from family activities that according to the Core and Balance Model (Zabriskie et al., 2001) could jeopardize overall levels of family functioning by eliminating opportunities for building or improving family adaptability, cohesion, or communication.

#### **7.2.2 Sexuality and intimacy**

74 Novel Strategies in Lymphedema

Radina (2009) found that for some women with breast cancer-related lymphedema, lifestyle modifications extend beyond daily activities such as dressing, bathing, cooking, and housekeeping into the realm of leisure. When it comes to leisure activities, wives and mothers who are often responsible for family management, are likely to be the ones creating time and space for other family members' independent leisure activities (e.g., backing cupcakes for her son's football team party, driving children to music lessons). Because of these other responsibilities, women's independent leisure is often sacrificed so that they can accomplish these other tasks for their families (Henderson, Bialeschki, Shaw, & Freysinger,

For women, their own participation in leisure activities in general, whether engaged in individually or with their families, may act as a buffer against stressful life events such as breast cancer and breast cancer-related lymphedema (Pondé & Santana, 2000). Thus, the continued participation of women with lymphedema in leisure activities appears valuable for sustaining their quality of life after breast cancer treatment. At the same time, family leisure is important for understanding family functioning (Zabriski & McCormick, 2001), particularly in the context of chronic health conditions and health-related disabilities (Jo, Kosciulek, Huh, & Holecek, 2004). Radina (2009) found that breast cancer-related lymphedema can create serious limitations that can impact both family functioning and

Family interaction in the context of leisure enhances the family's ability to remain stable (Orthner & Mancini, 1990). In fact, researchers have demonstrated that there is a positive relationship between family leisure engagement, family satisfaction, and family quality of life (Zabriskie & McCormick, 2003). The Core and Balance Model of Family Leisure Functioning (Zabriskie, 2000; Zabriskie & McCormick, 2001) suggests that family adaptability (i.e., the family's ability to be flexible and change), cohesion (i.e., closeness, emotional bonding), and communication are facilitated through family members' joint engagement in family-based leisure activities (Zabriskie & McCormick, 2001). These can include both core and balance leisure activities. Core leisure activities are "common everyday, low-cost, relatively accessible, and often home-based activities that families do frequently" (Zabriskie & McCormick, 2003, p. 168) including such activities as playing a game, e-mailing or instant messaging with family members, and making/eating dinner together (Zabriskie & McCormick, 2001). Core leisure activities tend to be associated with the maintenance of family cohesion and thus families who perceived themselves as having high levels of emotional closeness report engaging in more core leisure activities (Zabriskie, McCormick, & Austin, 2001). Balance leisure activities are "less common, less frequent, more out of the ordinary, and usually not home based thus providing novel experiences" (Zabriskie & McCormick, 2003, p. 168) including such activities as family travel, family reunions, and special family events (Zabriskie & McCormick, 2001). Balance activities tend to be associated with maintaining family adaptability (Zabriskie et al., 2001). According to the Core and Balance Model, in order to have healthier family functioning that results from increased levels of family communication, families should participate in both core and balance activities that enhance both family cohesion and adaptability (Zabriskie &

The role that family leisure plays generally also applies to families in which there is a chronically ill or disabled member (i.e., lymphedema). For such families participating in

1999).

participation in leisure.

McCormick, 2003).

Sexuality can be examined as an interaction of biological, psychological, and social domains of life (Lindau, Laumann, Levinson, & Waite, 2003; National Institute on Aging, 2005). How individuals feel about themselves as sexual beings is impacted by a combination of all three of these areas. As women with breast cancer-related lymphedema have already faced breast cancer, their feelings about sexuality and intimacy are intertwined with their breast cancer and lymphedema experiences. Thus, it may not be possible to completely distinguish between body image issues, feelings of sexuality, and the impact on sexual relationships brought about by breast cancer and those resulting from lymphedema.

Researchers have explored the impact of breast cancer on sexuality and sexual relationships (e.g., Henson, 2002). This work has included investigations into the impact of breast cancer and its treatment on hormones and sexual functioning, attitudes of a romantic partner, the impact of fatigue brought about by treatment on sexual relationships, and how an altered body image resulting from (breast) cancer can impact one's sexuality and sexual relationships (Gould, Grassau, Manthorne, Gray, & Fitch, 2006). Research also have focused on how there tends to be a lack of information on how breast cancer and its treatment can impact sexuality that is provided to breast cancer patient and their partners (Gould et al., 2006; Henson, 2002).

With breast cancer-related lymphedema, women may experience changes in their appearance as well as pain and physical limitations due to swelling (Passik & McDonald, 1998). As sexuality is connected to a woman's feelings about herself and her body, not only the experience of breast cancer, but also the development of lymphedema can have a serious impact on her views of herself as sexual and her willingness to be physical with a partner. Having survived breast cancer to now have to contend with breast cancer-related lymphedema can be seen "as a secondary blow to their physical and emotional well-being," which includes their intimate relationships with others (Passik and McDonald, 1998, p. 2818). Research (e.g., Koch et al., 2005; Radina, Watson, & Faubert, 2009; Wiederman &

Preparing for and Coping with Breast Cancer-Related Lymphedema 77

The first assumption is that families are made up of multiple actors who interact based on established patterns of functioning that are governed by rules that can be both explicit and implicit (Bigner, 1998). Second, new or revised patterns of functioning can result when a stressor (e.g., breast cancer) is encountered by the family (M. A. McCubbin & H. I., McCubbin, 1991; 1996; Olson, Lavee, & McCubbin, 1988). Third, the introduction of that stressor to the family allows for established patterns of functioning to become apparent when they otherwise might not be (Ingoldsby, Smith, & Miller, 2004; Molassiotis, 1997). Fourth, quality of family life is subjective and situation-dependent (McCabe et al., 2008).

As is detailed in Figure 5, the theory of Health-Related Family Quality of Life is made up of three overarching concepts: emotional closeness, family self-efficacy, and family functioning. *Emotional closeness* includes feelings of psychological or affectional closeness toward and/or between family members as well as such feelings toward the family as a unit (Bengtson, 1991; Poston et al., 2003). At the same time, the concept of emotional closeness also includes family communication as a way of facilitating and demonstrating closeness (Bigner, 1998; M. A. McCubbin & H. I., McCubbin, 1991; 1996; Poston et al., 2003). Family communication is made up of family members' feelings regarding the quality, quantity, frequency, and content of this communication (Bengston, 1991). Lastly, the concept of emotional closeness also includes social support-both among family members and for the family as a unit from those outside the family. Social support can also be considered a resource that the family uses in managing the quality of their family life (Hill, 1949; Patterson, 2002; Poston et al., 2003). *Family Self-Efficacy* refers to the families meaningmaking about themselves as a unit and the illness (i.e., sense of coherence), in this case breast cancer. Hill (1949) and others (e.g., Anderson, 1993; Caplan, 1987; McCabe et al., 2008) point to the importance of appraisal of stressors as essential to understanding how the stressor will be handled. That is, if a family considers the stressor to be catastrophic, this may have a negative influence on family quality of life in that it may be seen as irrevocable damaged. As part of this meaning-making, family self-efficacy includes family members' sense of both family strengths (Smith-Bird & Turnbull, 2005) and their ability to cope with challenges (i.e., possibly based on the family's history of how they face challenges and their success with overcoming them; Hill, 1949; M. A. McCubbin & H. I., McCubbin, 1991; 1996; Mellon & Northouse, 2001; Patterson, 2002). Lastly, *Family Functioning* consists of family members' roles and responsibilities (e.g., family care, daily activities, getting help) as well as their satisfaction with how well the family meets individual and family unit needs (Bigner,

1998; Ingoldsby et al., 2004; Park et al., 2003; Rettig & Leichtentritt, 1999).

that families utilize when faced with a stressor.

The theory of Health-Related Family Quality of Life offers three propositions about how health-related family quality of life functions. First, the theory of Health-Related Family Quality of Life is based on family members' perceptions of emotional closeness, family efficacy, and satisfaction with needs being met. Second, changes in family quality of life are based on perceptions of changes in emotional closeness, family self-efficacy, and patterns of functioning. Third, emotional closeness and family self-efficacy are considered resources

The application of the theory of Health-Related Family Quality of Life sheds light on the varying factors that can contribute to how a family reacts to and copes with breast cancerrelated lymphedema. For some families these factors may already be working well meaning that they will be predisposed to maintain a positive health-related quality of life in the

Hurst, 1997) has highlighted the negative ways in which women with breast-cancer related lymphedema feel about their bodies and how these feeling can take away from their desire to engage in sexual activity with a partner. Radina et al (2009) and Gould et al. (2006) found that the disfiguring aspects of breast cancer as well as breast cancer-related lymphedema made women feel unattractive and self-conscious about their bodies. Radina et al (2009) also found that women with breast-cancer related lymphedema expressed feeling that current or future sexual partners might not find them sexy because of the lymphedema and/or the compression garments that they need to be wear to treat their conditions.

There are numerous studies that explore the connection of sexual satisfaction, self or body image, and physical disability (e.g., Kedde & van Berlo, 2006; Taleporos, Dip, & McCabe, 2002; Galvin, 2005). Lymphedema can be not only be a condition with disfiguring effects but also debilitating ones. Galvin (2005) studied narratives of disabled people with a diverse range of disability and impairment. Based on this research, the term "disabled identity" emerged to reflect a self-perception that is affected by appearance, sexuality, and the negative attitudes of others. Shame and fear of rejection were related to reactions from others for those whose impairment was evident or visible. Feelings of loss of attractiveness, negative reactions of others, and internalized societal messages about the asexuality of disabled people contributed to feelings of loss of sexuality in many of the narratives (Galvin, 2005). Although not a "disability," because of the disfiguring and disabling aspects of the condition of lymphedema, the "disabled identity," which is impacted by an internalization of how others view this condition, can negatively impact sexuality and one's desire to be sexual with others.

#### **7.2.3 Family quality of life**

Radina and Armer (2004) explored outcomes for women with breast cancer-related lymphedema within the context of their families using the Resiliency Model of Family Stress, Adjustment, and Adaptation (M. A. McCubbin & H. I. McCubbin, 1996). They found instances where participants described themselves and their families as either adjusting (i.e., making small changes in family patterns of functioning in order to cope with lymphedema), adapting (i.e., making major changes in family patterns of functioning in order to cope with lymphedema), or living in crisis. Specifically, those families who were resilient had shared perception of the limitations brought on by lymphedema as being manageable and something that could be incorporated into patterns of daily living. At the same time, the more resilient families pulled together as a family to make necessary changes (e.g., the entire family focusing on the lymphedema and supporting the patient, the patient or her spouse changing jobs, using humor and inside jokes). The ingenuity and perseverance demonstrated by resilient families suggest that the families of women with breast cancerrelated lymphedema can be resilient in coping with lymphedema.

One way to think about family life in the context of breast cancer-related lymphedema is to consider the concept of health-related family quality of life. Health-related family quality of life refers to a state of being for families in the context of one or more family members' illnesses as well as the processes that families use to cope. Below I provide an overview of a theory of Health-Related Family Quality of Life whose purpose is to provide a model of understanding what family quality of life is within the specific context of breast cancer and, by extension, breast cancer-related lymphedema. Below the assumptions, concepts, and propositions of this theory of Health-Related Family Quality of Life are presented.

Hurst, 1997) has highlighted the negative ways in which women with breast-cancer related lymphedema feel about their bodies and how these feeling can take away from their desire to engage in sexual activity with a partner. Radina et al (2009) and Gould et al. (2006) found that the disfiguring aspects of breast cancer as well as breast cancer-related lymphedema made women feel unattractive and self-conscious about their bodies. Radina et al (2009) also found that women with breast-cancer related lymphedema expressed feeling that current or future sexual partners might not find them sexy because of the lymphedema and/or the

There are numerous studies that explore the connection of sexual satisfaction, self or body image, and physical disability (e.g., Kedde & van Berlo, 2006; Taleporos, Dip, & McCabe, 2002; Galvin, 2005). Lymphedema can be not only be a condition with disfiguring effects but also debilitating ones. Galvin (2005) studied narratives of disabled people with a diverse range of disability and impairment. Based on this research, the term "disabled identity" emerged to reflect a self-perception that is affected by appearance, sexuality, and the negative attitudes of others. Shame and fear of rejection were related to reactions from others for those whose impairment was evident or visible. Feelings of loss of attractiveness, negative reactions of others, and internalized societal messages about the asexuality of disabled people contributed to feelings of loss of sexuality in many of the narratives (Galvin, 2005). Although not a "disability," because of the disfiguring and disabling aspects of the condition of lymphedema, the "disabled identity," which is impacted by an internalization of how others view this

compression garments that they need to be wear to treat their conditions.

condition, can negatively impact sexuality and one's desire to be sexual with others.

related lymphedema can be resilient in coping with lymphedema.

Radina and Armer (2004) explored outcomes for women with breast cancer-related lymphedema within the context of their families using the Resiliency Model of Family Stress, Adjustment, and Adaptation (M. A. McCubbin & H. I. McCubbin, 1996). They found instances where participants described themselves and their families as either adjusting (i.e., making small changes in family patterns of functioning in order to cope with lymphedema), adapting (i.e., making major changes in family patterns of functioning in order to cope with lymphedema), or living in crisis. Specifically, those families who were resilient had shared perception of the limitations brought on by lymphedema as being manageable and something that could be incorporated into patterns of daily living. At the same time, the more resilient families pulled together as a family to make necessary changes (e.g., the entire family focusing on the lymphedema and supporting the patient, the patient or her spouse changing jobs, using humor and inside jokes). The ingenuity and perseverance demonstrated by resilient families suggest that the families of women with breast cancer-

One way to think about family life in the context of breast cancer-related lymphedema is to consider the concept of health-related family quality of life. Health-related family quality of life refers to a state of being for families in the context of one or more family members' illnesses as well as the processes that families use to cope. Below I provide an overview of a theory of Health-Related Family Quality of Life whose purpose is to provide a model of understanding what family quality of life is within the specific context of breast cancer and, by extension, breast cancer-related lymphedema. Below the assumptions, concepts, and

propositions of this theory of Health-Related Family Quality of Life are presented.

**7.2.3 Family quality of life** 

The first assumption is that families are made up of multiple actors who interact based on established patterns of functioning that are governed by rules that can be both explicit and implicit (Bigner, 1998). Second, new or revised patterns of functioning can result when a stressor (e.g., breast cancer) is encountered by the family (M. A. McCubbin & H. I., McCubbin, 1991; 1996; Olson, Lavee, & McCubbin, 1988). Third, the introduction of that stressor to the family allows for established patterns of functioning to become apparent when they otherwise might not be (Ingoldsby, Smith, & Miller, 2004; Molassiotis, 1997). Fourth, quality of family life is subjective and situation-dependent (McCabe et al., 2008).

As is detailed in Figure 5, the theory of Health-Related Family Quality of Life is made up of three overarching concepts: emotional closeness, family self-efficacy, and family functioning. *Emotional closeness* includes feelings of psychological or affectional closeness toward and/or between family members as well as such feelings toward the family as a unit (Bengtson, 1991; Poston et al., 2003). At the same time, the concept of emotional closeness also includes family communication as a way of facilitating and demonstrating closeness (Bigner, 1998; M. A. McCubbin & H. I., McCubbin, 1991; 1996; Poston et al., 2003). Family communication is made up of family members' feelings regarding the quality, quantity, frequency, and content of this communication (Bengston, 1991). Lastly, the concept of emotional closeness also includes social support-both among family members and for the family as a unit from those outside the family. Social support can also be considered a resource that the family uses in managing the quality of their family life (Hill, 1949; Patterson, 2002; Poston et al., 2003). *Family Self-Efficacy* refers to the families meaningmaking about themselves as a unit and the illness (i.e., sense of coherence), in this case breast cancer. Hill (1949) and others (e.g., Anderson, 1993; Caplan, 1987; McCabe et al., 2008) point to the importance of appraisal of stressors as essential to understanding how the stressor will be handled. That is, if a family considers the stressor to be catastrophic, this may have a negative influence on family quality of life in that it may be seen as irrevocable damaged. As part of this meaning-making, family self-efficacy includes family members' sense of both family strengths (Smith-Bird & Turnbull, 2005) and their ability to cope with challenges (i.e., possibly based on the family's history of how they face challenges and their success with overcoming them; Hill, 1949; M. A. McCubbin & H. I., McCubbin, 1991; 1996; Mellon & Northouse, 2001; Patterson, 2002). Lastly, *Family Functioning* consists of family members' roles and responsibilities (e.g., family care, daily activities, getting help) as well as their satisfaction with how well the family meets individual and family unit needs (Bigner, 1998; Ingoldsby et al., 2004; Park et al., 2003; Rettig & Leichtentritt, 1999).

The theory of Health-Related Family Quality of Life offers three propositions about how health-related family quality of life functions. First, the theory of Health-Related Family Quality of Life is based on family members' perceptions of emotional closeness, family efficacy, and satisfaction with needs being met. Second, changes in family quality of life are based on perceptions of changes in emotional closeness, family self-efficacy, and patterns of functioning. Third, emotional closeness and family self-efficacy are considered resources that families utilize when faced with a stressor.

The application of the theory of Health-Related Family Quality of Life sheds light on the varying factors that can contribute to how a family reacts to and copes with breast cancerrelated lymphedema. For some families these factors may already be working well meaning that they will be predisposed to maintain a positive health-related quality of life in the

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Fig. 7. Theory of Health-Related Family Quality of Life

#### **8. Conclusion**

Up to 40% of breast cancer patients are likely to develop breast cancer-related lymphedema. Thus, patients and their family members must learned to not only prepare for but cope with this often disabling chronic condition. Thus, the focus of this chapter was on patient (and family member/caregiver) education regarding strategies for early detection, risk reduction, and management/self-care and the individual and family level psychosocial impacts of coping with breast cancer-related lymphedema. The topics covered in this chapter were chosen with the intention of informing readers (e.g., physicians, nursing, social workers, family therapists, family life educators, and others who work with patients and their families) about the needs of patients and their family members and provide strategies to meet the needs of patients and families. In this way, wide ranging support for patients and their family members would be encouraged and implemented throughout the trajectory of patient care.

#### **9. References**

78 Novel Strategies in Lymphedema

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Up to 40% of breast cancer patients are likely to develop breast cancer-related lymphedema. Thus, patients and their family members must learned to not only prepare for but cope with this often disabling chronic condition. Thus, the focus of this chapter was on patient (and family member/caregiver) education regarding strategies for early detection, risk reduction, and management/self-care and the individual and family level psychosocial impacts of coping with breast cancer-related lymphedema. The topics covered in this chapter were chosen with the intention of informing readers (e.g., physicians, nursing, social workers, family therapists, family life educators, and others who work with patients and their families) about the needs of patients and their family members and provide strategies to meet the needs of patients and families. In this way, wide ranging support for patients and their family members would be encouraged and implemented throughout the trajectory of

patients and their family members thrive.

Fig. 7. Theory of Health-Related Family Quality of Life

**8. Conclusion** 

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**5** 

*Italy* 

**Pelvic Lymphedema in Rectal Cancer** 

Clarke's Second Law is: "The only way of discovering the limits of the possible is to venture a little way past them into the impossible" (Clarke, 1962). Pelvic lymphedema issues this

The prognosis for pelvic malignancies has improved in recent years mainly due to advanced technologies and better knowledge of the pathways of cancer spread. Lymphadenectomy is the most important prognostic factor in pelvic malignancies, a finding that has substantially changed surgical approaches from a "quantitative" premise to a more "qualitative" nature giving priority to the psycho-physical integrity of cancer patients by limiting the surgical intervention (Breyer et al, 2008; Mills et al, 2006; Desnoo & Faithfull 2006; Greco et al, 2006). However, despite progress made by the conservative surgical approach for rectal cancer, the development of functional abnormalities in patients undergoing conservative surgery has become more evident (Ortiz & Armendariz, 1996). These dysfunctional pathology are associated with symptoms similar to those of the pre-surgery pelvic pathology. Most importantly these problems are considered a major public health issue representing one third of costs of colorectal cancer treatment, even if the massive economic burden of disability has received limited attention (Selke, 2003). Although theories including neural damage, reduction of capacity and compliance of organs, and sensory loss have been already proposed, no clear evidence of a direct correlation between such symptoms and surgical damage exists. Additionally, such disabilities do not depend on the extent of the surgical intervention (conservative versus radical), on the use of concomitant post-operative radio-chemotherapy or the gender (Kakodkar et al, 2006). Fortunately, patients have been shown to respond to biofeedback reeducation of the pelvic floor, with or without added

We hypotized that pelvic surgery, regardless of the extra-peritoneal organs, results in the loss of continuity of the pelvic region, as key event with the following reduction in fatty tissue where the lymph node stations are mostly concentrated. Therefore we suggest that pelvic lymphadenectomy should be followed by a pelvic lymphedema (Vannelli et al, 2009). Once identified, lymphedema does not undergo significant reabsorption and may lead to serious chronic pathology with severe functional impairment of pelvic organs ((Zermann et al, 2001). Yet, the mechanisms and pathways that involve lymphedema in pelvic pathology are still unknown and needs to be investigated. We examined, by chance, post surgery

**1. Introduction** 

psychotherapy (Devroede, 1999).

challenge.

*Fondazione IRCCS "Istituto Nazionale dei Tumori", Milan,* 

Alberto Vannelli and Luigi Battaglia


## **Pelvic Lymphedema in Rectal Cancer**

Alberto Vannelli and Luigi Battaglia

*Fondazione IRCCS "Istituto Nazionale dei Tumori", Milan, Italy* 

#### **1. Introduction**

88 Novel Strategies in Lymphedema

Zabriskie, R. (2000). *An examination of family and leisure behaviors among families with middle* 

Zabriskie, R., & McCormick, B. (2001). The influences of family leisure patterns on

Zabriskie, R., & McCormick, B. (2003). Parent and child perspectives of family leisure

perceptions of family functioning. *Family Relations, 50*(3), 66-74.

189.

*school aged children*. Unpublished dissertation. Indiana University, Bloomington, IN.

involvement and satisfaction with family life. *Journal of Leisure Research, 35*(2), 163-

Clarke's Second Law is: "The only way of discovering the limits of the possible is to venture a little way past them into the impossible" (Clarke, 1962). Pelvic lymphedema issues this challenge.

The prognosis for pelvic malignancies has improved in recent years mainly due to advanced technologies and better knowledge of the pathways of cancer spread. Lymphadenectomy is the most important prognostic factor in pelvic malignancies, a finding that has substantially changed surgical approaches from a "quantitative" premise to a more "qualitative" nature giving priority to the psycho-physical integrity of cancer patients by limiting the surgical intervention (Breyer et al, 2008; Mills et al, 2006; Desnoo & Faithfull 2006; Greco et al, 2006).

However, despite progress made by the conservative surgical approach for rectal cancer, the development of functional abnormalities in patients undergoing conservative surgery has become more evident (Ortiz & Armendariz, 1996). These dysfunctional pathology are associated with symptoms similar to those of the pre-surgery pelvic pathology. Most importantly these problems are considered a major public health issue representing one third of costs of colorectal cancer treatment, even if the massive economic burden of disability has received limited attention (Selke, 2003). Although theories including neural damage, reduction of capacity and compliance of organs, and sensory loss have been already proposed, no clear evidence of a direct correlation between such symptoms and surgical damage exists. Additionally, such disabilities do not depend on the extent of the surgical intervention (conservative versus radical), on the use of concomitant post-operative radio-chemotherapy or the gender (Kakodkar et al, 2006). Fortunately, patients have been shown to respond to biofeedback reeducation of the pelvic floor, with or without added psychotherapy (Devroede, 1999).

We hypotized that pelvic surgery, regardless of the extra-peritoneal organs, results in the loss of continuity of the pelvic region, as key event with the following reduction in fatty tissue where the lymph node stations are mostly concentrated. Therefore we suggest that pelvic lymphadenectomy should be followed by a pelvic lymphedema (Vannelli et al, 2009).

Once identified, lymphedema does not undergo significant reabsorption and may lead to serious chronic pathology with severe functional impairment of pelvic organs ((Zermann et al, 2001). Yet, the mechanisms and pathways that involve lymphedema in pelvic pathology are still unknown and needs to be investigated. We examined, by chance, post surgery

Pelvic Lymphedema in Rectal Cancer 91

answer the question ''how does pelvic lymphedema occur?" During surgery the main responsible of the damage should be detected because if, not promptly treated, it can result in a chronic disease. However, to promptly institute the most suitable therapy, we should understand ''why does the lymphedema occurs?" and identify the first action. When we talk about postoperative disorders of pelvic surgery, two areas are identified: perineum and extraperitoneal region (Corton, 2005). Perineum consists of soft tissues which close the lower pelvic cavity. This region is sited between the upper portions of the two thighs, to which anal canal, extraperitoneal rectum and external genitals are connected. An ideal transversal line joining the two ischiatic eminences divides the region into two triangles: one anterior, or urogenital perineum, and the other, posterior or anorectal perineum. The subcutaneous layer is bulky in the side walls and posteriorly where it continues with the fat of the

Fig. 1. Illustration of the drainage pathways of the lymphatic vessels in the pelvic area (orange lines correspond to lymphadenectomy and eventfully lymphatic spread).

This allows the proliferation of a rich and branched lymphatic net with numerous lymph nodal stations. The extraperitoneal pelvic space is sited between the peritoneum covering the pelvic organs, and the pelvic diaphragm. In the pelvic cavity the peritoneum is separated from the walls which delimit the cavity by the surrounding and supporting fatty extraperitoneal tissue. This creates a sort of floating effect of the organs contained in the pelvis. The fatty tissue forms the two thirds of the total volume and contains important

ischiorectal fossae.

lymphedema in 13 patients submitted to our hospital for colorectal adenocarcinoma, by comparing MRI of the abdominal area of the pre and post surgery. Interestingly, comparison of dynamic MRI images obtained in different phases of the patient's management enabled identification of pelvic floor lymphedema after surgical intervention for colorectal adenocarcinoma.

#### **2. Vannelli's theory**

The complete description of the lymphatic vessels goes back to 17th century. However, some investigators have only recently recognized the impact of lymphology on the treatment of tumours, both from research and clinical points of view. This sudden increased interest has led to study oncological and functional lymphatic disease, in particular related to lymphedema. It is known that each lymphadenectomy is associated to a lymphedema. Lymphedema is defined as a chronic and debilitating condition and it is correct to suggest the presence of a lymphedema also in the pelvic area related to the oncological surgery treatment: a pelvic lymphedema, that we will call blind lymphedema, i.e. with symptoms but with no signs. We make an introduction. Are we sure to know the meaning of lymphedema? Lymphedema is what we know because we can see it: upper limbs, lower limbs, even neck, scrotum or pubis (Thorat, 2006; Fang et al, 2008; Vignes & Trévidic, 2005). Probably there is a lymphedema that we do not know only because we cannot see it. The Roman playwright Terentius wrote: ''But 'even if the old masters have discovered everything, one thing will be always new, - the application and the scientific study and classification of the discoveries made by others. " (Gummere, 1917-28). To clear our mind of any doubt, it is necessary to make a step backwards. In the scientific discussion lymphedema is not a ''meaning" that does not define or indicate a disorder. It is rather defined by its characteristics, i.e. what determines a lymphedema: interstitial retention of proteins, tissue inflammation, fatty tissue hypertrophy, fibrosis, progressive pathological condition, but this is not lymphedema (Warren et al, 2007). The only acceptable definition of lymphedema should be the alteration of the lymphatic vessels due to a (primary) malformation or a (secondary) mechanical damage. Basing on this definition, a new model of lymphedema can be therefore assumed: pelvic lymphedema, that is the alteration of lymphatic vessels associated to a pelvis mechanical damage. The pelvic disorders are extremely frequently and occur regardless of gender, type of surgery or concomitant medical treatment (pre- or post-operative radiotherapy). The study on pelvic disorders immediately is found to be of difficult execution and even without instrumental evidence of any damage, an important symptomatology can be present. The available examinations for the study of the various pelvic components are numerous: uroflowmetry and cystography to investigate the bladder; rectomanometry or electrical stimulation by means of evoked potentials of pudendal nerve; defecography for the investigation of the rectum, just to mention some of them. However, the available data in the literature do not give any satisfactory response concerning the patients with negative tests but with clinically relevant disorders (Antolak et al, 2002). Perineology has acquired higher importance in the recent years: a multispecialistic discipline of multifactorial interest of pelvic diseases with rehabilitation purpose (Peters et al, 2008). After a careful follow-up of the patients operated for pelvic tumours, we observed that all the patients referring to the perineology centres had a relevant benefit from the rehabilitation treatment reducing the complications rate and, in some cases, preventing them (Bai et al, 2006; Brown & Seow-Choen, 2000). This could

lymphedema in 13 patients submitted to our hospital for colorectal adenocarcinoma, by comparing MRI of the abdominal area of the pre and post surgery. Interestingly, comparison of dynamic MRI images obtained in different phases of the patient's management enabled identification of pelvic floor lymphedema after surgical intervention

The complete description of the lymphatic vessels goes back to 17th century. However, some investigators have only recently recognized the impact of lymphology on the treatment of tumours, both from research and clinical points of view. This sudden increased interest has led to study oncological and functional lymphatic disease, in particular related to lymphedema. It is known that each lymphadenectomy is associated to a lymphedema. Lymphedema is defined as a chronic and debilitating condition and it is correct to suggest the presence of a lymphedema also in the pelvic area related to the oncological surgery treatment: a pelvic lymphedema, that we will call blind lymphedema, i.e. with symptoms but with no signs. We make an introduction. Are we sure to know the meaning of lymphedema? Lymphedema is what we know because we can see it: upper limbs, lower limbs, even neck, scrotum or pubis (Thorat, 2006; Fang et al, 2008; Vignes & Trévidic, 2005). Probably there is a lymphedema that we do not know only because we cannot see it. The Roman playwright Terentius wrote: ''But 'even if the old masters have discovered everything, one thing will be always new, - the application and the scientific study and classification of the discoveries made by others. " (Gummere, 1917-28). To clear our mind of any doubt, it is necessary to make a step backwards. In the scientific discussion lymphedema is not a ''meaning" that does not define or indicate a disorder. It is rather defined by its characteristics, i.e. what determines a lymphedema: interstitial retention of proteins, tissue inflammation, fatty tissue hypertrophy, fibrosis, progressive pathological condition, but this is not lymphedema (Warren et al, 2007). The only acceptable definition of lymphedema should be the alteration of the lymphatic vessels due to a (primary) malformation or a (secondary) mechanical damage. Basing on this definition, a new model of lymphedema can be therefore assumed: pelvic lymphedema, that is the alteration of lymphatic vessels associated to a pelvis mechanical damage. The pelvic disorders are extremely frequently and occur regardless of gender, type of surgery or concomitant medical treatment (pre- or post-operative radiotherapy). The study on pelvic disorders immediately is found to be of difficult execution and even without instrumental evidence of any damage, an important symptomatology can be present. The available examinations for the study of the various pelvic components are numerous: uroflowmetry and cystography to investigate the bladder; rectomanometry or electrical stimulation by means of evoked potentials of pudendal nerve; defecography for the investigation of the rectum, just to mention some of them. However, the available data in the literature do not give any satisfactory response concerning the patients with negative tests but with clinically relevant disorders (Antolak et al, 2002). Perineology has acquired higher importance in the recent years: a multispecialistic discipline of multifactorial interest of pelvic diseases with rehabilitation purpose (Peters et al, 2008). After a careful follow-up of the patients operated for pelvic tumours, we observed that all the patients referring to the perineology centres had a relevant benefit from the rehabilitation treatment reducing the complications rate and, in some cases, preventing them (Bai et al, 2006; Brown & Seow-Choen, 2000). This could

for colorectal adenocarcinoma.

**2. Vannelli's theory** 

answer the question ''how does pelvic lymphedema occur?" During surgery the main responsible of the damage should be detected because if, not promptly treated, it can result in a chronic disease. However, to promptly institute the most suitable therapy, we should understand ''why does the lymphedema occurs?" and identify the first action. When we talk about postoperative disorders of pelvic surgery, two areas are identified: perineum and extraperitoneal region (Corton, 2005). Perineum consists of soft tissues which close the lower pelvic cavity. This region is sited between the upper portions of the two thighs, to which anal canal, extraperitoneal rectum and external genitals are connected. An ideal transversal line joining the two ischiatic eminences divides the region into two triangles: one anterior, or urogenital perineum, and the other, posterior or anorectal perineum. The subcutaneous layer is bulky in the side walls and posteriorly where it continues with the fat of the ischiorectal fossae.

Fig. 1. Illustration of the drainage pathways of the lymphatic vessels in the pelvic area (orange lines correspond to lymphadenectomy and eventfully lymphatic spread).

This allows the proliferation of a rich and branched lymphatic net with numerous lymph nodal stations. The extraperitoneal pelvic space is sited between the peritoneum covering the pelvic organs, and the pelvic diaphragm. In the pelvic cavity the peritoneum is separated from the walls which delimit the cavity by the surrounding and supporting fatty extraperitoneal tissue. This creates a sort of floating effect of the organs contained in the pelvis. The fatty tissue forms the two thirds of the total volume and contains important

Pelvic Lymphedema in Rectal Cancer 93

honeycomb pattern above the fascia between muscle and subcutaneous fat, with evident thickening of the dermis (Witte, 2002). Although it is generally difficult to differentiate primary from secondary lymphedema, MRI is able to discriminate lymphedema from lipoedema and phlebedema (Lohrmann et al, 2009; Aström et al, 2001). Our standard procedure for pre-operative patients is an MRI with Gadolinium. On the other hand, for follow-ups, the MRI is indicated only for a suspicious local recurrence. Thirteen patients were selected for our study to be evaluated with MRI but with a different approach. In details, along with the above described standard procedures, a sequence of fat-suppressed T2-weighted (FST2) and diffusion weighted T2-weighted (DIT2) were performed, as those are the most efficient techniques to evaluate lymphedema. Specifically, to evaluate lymphedema using FST2 the signal should be increase as the presence of increasing degrees of edema related to active inflammation (Delfaut et al, 1999). Additionally, DIT2 has been found to improve the detection of edema and herein introduced to detect the lymphedema degree (Ebisu T, et al 1993). Moreover when lipoedema occurs, MRI is able to confirm that the peripheral lymphatic system is normal while soft tissue swelling consists solely of fat,

At the time of the analyses thirteen patients were admitted to our department, for colo-rectal adenocarcinoma. Five were male and eight females with a median age of 66, ranging from 45 to 72 years. In all patients, a whole body mass index (BMI) was calculated: range 25-35, mean 29.9. Cases included patients with adenocarcinoma of the sigmoid colon without metastases and rectum without metastases. Four patients have been affected by intraperitoneal adenocarcinoma: one sigmoid and three upper third rectal cancer (one male and three female) and nine extra-peritoneal adenocarcinoma: four middle third rectal cancer and five lower third rectal cancer (four male and five female). The patients affected by intraperitoneal adenocarcinoma has been submitted to: one resection of sigmoid colon and three anterior resection of upper rectum. Three patient presented stage IIa and one stage I. The patients affected by extra-peritoneal adenocarcinoma has been submitted to seven anterior resection of the rectum and two total resection of the rectum with colo-endo anal anastomosis. Seven patient presented stage I and two stage 0. Nine patients with an extraperitoneal lesion underwent a resection of middle and lower third of rectum with regional lymphadenectomy, while the other patients with an intra-peritoneal lesion required resection of sigmoid colon and upper third of the rectum with regional lymphadenectomy. A sagittal and coronal T1 MRI, as well as FST2 and DIT2 images on the axial plane were requested for the seven patients who underwent anterior rectal resection, which involved the pelvic floor, as a result of extra-peritoneal location of the adenocarcinoma (middle and lower third of the rectum). There is no clear evidence of the pelvic lymphedema or lymphatic alterations in the pre-operative MRI performed 1 week prior to surgery for all patients. However, a post-operative MRI follow-up performed six months flowing discharge from the hospital revealed in seven patients a lymphatic 'stipes-like' elements within the presacral adipose tissue with compression of the sacro-sciatic ligaments and bladder, all indicative of lymphatic alterations. Moreover in nine patients, the area of edema and venous congestion of pelvis together with compression of pelvic organs indicated by MRI signals, were located far from the area of surgical intervention. Furthermore, in eight patients, with the phase of T1 acquisition, epifascial "lakes" related to the muscular bands located outside

and subcutaneous edema is absent.

**4. Result** 

lymph node stations. The pelvic floor can be considered as the centre supporting the perineal layer. It consists of a complex of muscles which are twisted together and close the pelvis in the bottom.

These muscles wrap the urinary (urethra and bladder) and reproductive (vagina in females and prostate in men) systems and form the anterior floor down to the anorectal apparatus (anus, rectum) which makes the posterior floor. Perineum is a dynamic organ and is continuously subject to our body weight. It especially has the duty to support the increases in intra-abdominal pressure due to the increases in loads, chronic conditions and natural events, such as the childbirth (Van der Putte, 2005). Pelvic surgery, regardless of the involved organs, results in the loss of continuity of the pelvic region as key event with the following reduction in fatty tissue where the lymph node stations are mostly concentrated (Andrade & Jacomo, 2007). Therefore, the occurrence of pelvic disorders, even though of difficult etiology, could be possible due to a surgery which is associated to a lymphadenectomy (Fig. 1). The presence of a lymphadenectomy, that can be considerably wide in some cases, should be followed by a lymphedema.

#### **3. Materials and methods**

#### **3.1 Patients**

Between March 1990 and January 2010, 6975 patients were operated for colo-rectal carcinoma in the Division of Colorectal Surgery at the Fondazione IRCCS "Istituto Nazionale dei Tumori", a non university teaching hospital in Milan, the Italy.

For the purpose of the study, information was collected both from medical records and a computerized database of patients admitted to our Division, between May 2008 and January 2010. To discriminate pelvic lymphedema we compared the extra-peritoneal adenocarcinoma (cases) with intra-peritoneal adenocarcinoma (controls) staging with MRI examination. Excluded from the analysis were patients with preoperative treatment, those patients with locoregional recurrence, previous pelvic surgery or patients with distant metastases and with more than one primary cancer. We regarded the rectum cut-off within 15 cm from the anal verge and intraperitoneal cut-off more than 12 cm from the anal verge. We identified a cohort of 13 patients with sigmoid colon and rectal adenocarcinoma. Bowel preparation and surgical techniques have been described in details (Leo et al, 2009). All patients had a pre-operative (one week before surgery) and post-operative (six months following discharge from the hospital) MRI examination. This study was approved by the institutional review board.

#### **3.2 Nuclear magnetic resonance**

In details, a 1.5-T high-resolution MRI system (Avanto; Siemens Medical Systems, Erlangen, Germany) was used for the pre operative stages and the follow-up of the patients. For the purpose of our study, the 13 patients were examined in the supine position with feet forward and measurements were obtained using the same system and by the same technician.

We consider the common features of lymphedema, usually observed in an MRI examination: circumferential edema, increased volume of subcutaneous tissue, and a honeycomb pattern above the fascia between muscle and subcutaneous fat, with evident thickening of the dermis (Witte, 2002). Although it is generally difficult to differentiate primary from secondary lymphedema, MRI is able to discriminate lymphedema from lipoedema and phlebedema (Lohrmann et al, 2009; Aström et al, 2001). Our standard procedure for pre-operative patients is an MRI with Gadolinium. On the other hand, for follow-ups, the MRI is indicated only for a suspicious local recurrence. Thirteen patients were selected for our study to be evaluated with MRI but with a different approach. In details, along with the above described standard procedures, a sequence of fat-suppressed T2-weighted (FST2) and diffusion weighted T2-weighted (DIT2) were performed, as those are the most efficient techniques to evaluate lymphedema. Specifically, to evaluate lymphedema using FST2 the signal should be increase as the presence of increasing degrees of edema related to active inflammation (Delfaut et al, 1999). Additionally, DIT2 has been found to improve the detection of edema and herein introduced to detect the lymphedema degree (Ebisu T, et al 1993). Moreover when lipoedema occurs, MRI is able to confirm that the peripheral lymphatic system is normal while soft tissue swelling consists solely of fat, and subcutaneous edema is absent.

#### **4. Result**

92 Novel Strategies in Lymphedema

lymph node stations. The pelvic floor can be considered as the centre supporting the perineal layer. It consists of a complex of muscles which are twisted together and close the

These muscles wrap the urinary (urethra and bladder) and reproductive (vagina in females and prostate in men) systems and form the anterior floor down to the anorectal apparatus (anus, rectum) which makes the posterior floor. Perineum is a dynamic organ and is continuously subject to our body weight. It especially has the duty to support the increases in intra-abdominal pressure due to the increases in loads, chronic conditions and natural events, such as the childbirth (Van der Putte, 2005). Pelvic surgery, regardless of the involved organs, results in the loss of continuity of the pelvic region as key event with the following reduction in fatty tissue where the lymph node stations are mostly concentrated (Andrade & Jacomo, 2007). Therefore, the occurrence of pelvic disorders, even though of difficult etiology, could be possible due to a surgery which is associated to a lymphadenectomy (Fig. 1). The presence of a lymphadenectomy, that can be considerably

Between March 1990 and January 2010, 6975 patients were operated for colo-rectal carcinoma in the Division of Colorectal Surgery at the Fondazione IRCCS "Istituto

For the purpose of the study, information was collected both from medical records and a computerized database of patients admitted to our Division, between May 2008 and January 2010. To discriminate pelvic lymphedema we compared the extra-peritoneal adenocarcinoma (cases) with intra-peritoneal adenocarcinoma (controls) staging with MRI examination. Excluded from the analysis were patients with preoperative treatment, those patients with locoregional recurrence, previous pelvic surgery or patients with distant metastases and with more than one primary cancer. We regarded the rectum cut-off within 15 cm from the anal verge and intraperitoneal cut-off more than 12 cm from the anal verge. We identified a cohort of 13 patients with sigmoid colon and rectal adenocarcinoma. Bowel preparation and surgical techniques have been described in details (Leo et al, 2009). All patients had a pre-operative (one week before surgery) and post-operative (six months following discharge from the hospital) MRI examination. This study was approved by the

In details, a 1.5-T high-resolution MRI system (Avanto; Siemens Medical Systems, Erlangen, Germany) was used for the pre operative stages and the follow-up of the patients. For the purpose of our study, the 13 patients were examined in the supine position with feet forward and measurements were obtained using the same system and by the same

We consider the common features of lymphedema, usually observed in an MRI examination: circumferential edema, increased volume of subcutaneous tissue, and a

Nazionale dei Tumori", a non university teaching hospital in Milan, the Italy.

wide in some cases, should be followed by a lymphedema.

pelvis in the bottom.

**3. Materials and methods** 

institutional review board.

technician.

**3.2 Nuclear magnetic resonance** 

**3.1 Patients** 

At the time of the analyses thirteen patients were admitted to our department, for colo-rectal adenocarcinoma. Five were male and eight females with a median age of 66, ranging from 45 to 72 years. In all patients, a whole body mass index (BMI) was calculated: range 25-35, mean 29.9. Cases included patients with adenocarcinoma of the sigmoid colon without metastases and rectum without metastases. Four patients have been affected by intraperitoneal adenocarcinoma: one sigmoid and three upper third rectal cancer (one male and three female) and nine extra-peritoneal adenocarcinoma: four middle third rectal cancer and five lower third rectal cancer (four male and five female). The patients affected by intraperitoneal adenocarcinoma has been submitted to: one resection of sigmoid colon and three anterior resection of upper rectum. Three patient presented stage IIa and one stage I. The patients affected by extra-peritoneal adenocarcinoma has been submitted to seven anterior resection of the rectum and two total resection of the rectum with colo-endo anal anastomosis. Seven patient presented stage I and two stage 0. Nine patients with an extraperitoneal lesion underwent a resection of middle and lower third of rectum with regional lymphadenectomy, while the other patients with an intra-peritoneal lesion required resection of sigmoid colon and upper third of the rectum with regional lymphadenectomy. A sagittal and coronal T1 MRI, as well as FST2 and DIT2 images on the axial plane were requested for the seven patients who underwent anterior rectal resection, which involved the pelvic floor, as a result of extra-peritoneal location of the adenocarcinoma (middle and lower third of the rectum). There is no clear evidence of the pelvic lymphedema or lymphatic alterations in the pre-operative MRI performed 1 week prior to surgery for all patients. However, a post-operative MRI follow-up performed six months flowing discharge from the hospital revealed in seven patients a lymphatic 'stipes-like' elements within the presacral adipose tissue with compression of the sacro-sciatic ligaments and bladder, all indicative of lymphatic alterations. Moreover in nine patients, the area of edema and venous congestion of pelvis together with compression of pelvic organs indicated by MRI signals, were located far from the area of surgical intervention. Furthermore, in eight patients, with the phase of T1 acquisition, epifascial "lakes" related to the muscular bands located outside

Pelvic Lymphedema in Rectal Cancer 95

peritoneal adenocarcinoma have been submitted to 7 anterior resection of the rectum and 2 total resection of the rectum with colo-endo anal anastomosis. In details, 7 patients presented stage I, and 2 stage 0. Nine patients with an extra-peritoneal lesion underwent a resection of middle and lower third of rectum with regional lymphadenectomy, while the other patients with an intra-peritoneal lesion required resection of sigmoid colon and upper third of the rectum with regional lymphadenectomy. Table II summarizes the MRI characteristics for each patient using 4 paramenters: stipes-like, edema and venous

1 no no no no no no no no

2 no no no no no no no no

3 no no no no no no no no

4 no no no no no no no no

5 no yes no yes no yes no yes

6 no no no yes no yes no yes

7 no no no yes no yes no no

8 no yes no yes no no no no

9 no yes no yes no yes no yes

10 no yes no yes no yes no no

11 no yes no yes no yes no yes

12 no yes no yes no yes no yes

13 no yes no yes no yes no yes

A sagittal and coronal T1 MRI, as well as FST2 and DIT2 images on the axial plane were requested for the 7 patients who underwent anterior rectal resection, which involved the pelvic floor, as a result of extra-peritoneal location of the adenocarcinoma (middle and lower third of the rectum). There is no clear evidence of the pelvic lymphedema or lymphatic alterations in the

pre-operative MRI performed 1 week prior to surgery for all patients (figure 2).

**post MRI pre MRI** 

**Epifascial "lakes" Lymphatic stasis in** 

**presacral space** 

**post** 

**post MRI pre MRI** 

congestion, epifascial 'lakes', lymphatic stasis in presacral space.

**Edema and venous congestion** 

**post MRI pre MRI** 

**Patient Stipes like** 

 **MRI pre MRI** 

Table 2. MRI characteristics

of the pelvic floor in gluteal muscles were identified. Additionally, in six patients, the DIT2 enabled the detection of moderate lymphatic stasis in the presacral space. On the other hand, the four patients who underwent resection of the sigmoid colon and upper third of the rectum (without pelvic involvement due to intra-peritoneal adenocarcinoma located more than 12 cm from the anal verge), had a different MRI outcome. In details, the axial second planes were amplified with acquisition of T1, FST2 and DIT2- weighted sagittal and coronal images through subtraction of adipose tissue signals on the axial planes. Preoperative MRI revealed no pelvic lymphedema or alterations of the pelvic lymphatics in these patients. Also the post-operative follow-up performed six months after discharge from the hospital, showed no evidence of pelvic wall edema. Two patients, submitted to resection of the sigmoid colon, presented mild signal intensification in the lower part of the rectal abdominal muscle (figure 6). Overall, there are no signs of lymphatic congestion anywhere within the pelvic wall were noted in the four patients with intra-peritoneal surgery. Table I summarizes surgery information for each patient. Thirteen patients were admitted to our department for colo-rectal adenocarcinoma. Five were males and 8 females with a median age of 66, ranging from 45 to 72 years. In all patients, a whole body mass index (BMI) was calculated: range 25-35, mean 29.9.


Upper third rectal cancer (URC), Middle third rectal cancer (MRC), Low third rectal cancer (LRC), Resection of the sigmoid colon (RSC), Anterior resection of the rectum (ARR), Total resection of the rectum with colo-endo anal anastomosis (CEAA); Cancer classification with American Joint Committee on Cancer Staging 2010

Table 1. Characteristics of patients from May 2008 to January 2010

Cases included patients with adenocarcinoma of the sigmoid colon without metastases and of the rectum without metastases. Four patients have been affected by intra-peritoneal adenocarcinoma: one sigmoid and 3 upper third rectal cancer (1 male and 3 female) and 9 extra-peritoneal adenocarcinoma: 4 middle third rectal cancer and 5 lower third rectal cancer (4 male and 5 female). The patients affected by intra-peritoneal adenocarcinoma have been submitted to: one resection of sigmoid colon and 3 anterior resection of upper rectum. Specifically, 3 patients presented stage IIa and one stage I. The patients affected by extra-

of the pelvic floor in gluteal muscles were identified. Additionally, in six patients, the DIT2 enabled the detection of moderate lymphatic stasis in the presacral space. On the other hand, the four patients who underwent resection of the sigmoid colon and upper third of the rectum (without pelvic involvement due to intra-peritoneal adenocarcinoma located more than 12 cm from the anal verge), had a different MRI outcome. In details, the axial second planes were amplified with acquisition of T1, FST2 and DIT2- weighted sagittal and coronal images through subtraction of adipose tissue signals on the axial planes. Preoperative MRI revealed no pelvic lymphedema or alterations of the pelvic lymphatics in these patients. Also the post-operative follow-up performed six months after discharge from the hospital, showed no evidence of pelvic wall edema. Two patients, submitted to resection of the sigmoid colon, presented mild signal intensification in the lower part of the rectal abdominal muscle (figure 6). Overall, there are no signs of lymphatic congestion anywhere within the pelvic wall were noted in the four patients with intra-peritoneal surgery. Table I summarizes surgery information for each patient. Thirteen patients were admitted to our department for colo-rectal adenocarcinoma. Five were males and 8 females with a median age of 66, ranging from 45 to 72 years. In all patients, a whole body mass index (BMI) was

**Index Site of cancer Surgical** 

1 45 female 25 Sigmoid colon RSC IIa 2 72 male 35 URC ARR IIa 3 68 female 31,6 URC ARR IIa 4 70 female 25,8 URC ARR I 5 55 female 29,9 URC ARR I 6 60 male 28,8 MRC ARR I 7 59 female 29,6 LRC ARR 0 8 71 female 29,9 LRC ARR I 9 66 male 28,9 MRC ARR I 10 65 female 31,2 MRC CEAA 0 11 64 female 33,5 LRC ARR I 12 67 male 34,5 LRC CEEA I 13 67 male 33,3 LRC ARR I Upper third rectal cancer (URC), Middle third rectal cancer (MRC), Low third rectal cancer (LRC), Resection of the sigmoid colon (RSC), Anterior resection of the rectum (ARR), Total resection of the rectum with colo-endo anal anastomosis (CEAA); Cancer classification with American Joint Committee

Cases included patients with adenocarcinoma of the sigmoid colon without metastases and of the rectum without metastases. Four patients have been affected by intra-peritoneal adenocarcinoma: one sigmoid and 3 upper third rectal cancer (1 male and 3 female) and 9 extra-peritoneal adenocarcinoma: 4 middle third rectal cancer and 5 lower third rectal cancer (4 male and 5 female). The patients affected by intra-peritoneal adenocarcinoma have been submitted to: one resection of sigmoid colon and 3 anterior resection of upper rectum. Specifically, 3 patients presented stage IIa and one stage I. The patients affected by extra-

**procedure** 

**Cancer classification** 

calculated: range 25-35, mean 29.9.

**patient Age Sex Body Mass** 

Table 1. Characteristics of patients from May 2008 to January 2010

**Number** 

on Cancer Staging 2010

peritoneal adenocarcinoma have been submitted to 7 anterior resection of the rectum and 2 total resection of the rectum with colo-endo anal anastomosis. In details, 7 patients presented stage I, and 2 stage 0. Nine patients with an extra-peritoneal lesion underwent a resection of middle and lower third of rectum with regional lymphadenectomy, while the other patients with an intra-peritoneal lesion required resection of sigmoid colon and upper third of the rectum with regional lymphadenectomy. Table II summarizes the MRI characteristics for each patient using 4 paramenters: stipes-like, edema and venous congestion, epifascial 'lakes', lymphatic stasis in presacral space.


Table 2. MRI characteristics

A sagittal and coronal T1 MRI, as well as FST2 and DIT2 images on the axial plane were requested for the 7 patients who underwent anterior rectal resection, which involved the pelvic floor, as a result of extra-peritoneal location of the adenocarcinoma (middle and lower third of the rectum). There is no clear evidence of the pelvic lymphedema or lymphatic alterations in the pre-operative MRI performed 1 week prior to surgery for all patients (figure 2).

Pelvic Lymphedema in Rectal Cancer 97

Fig. 3. Post-operative period. Phase of FST2 acquisition. White arrows indicate lymphangitis in the sacral area; large open arrow indicates presacral fibrosis.

Fig. 4. Post-operative period. Phase of FST2 acquisition. Note lymphedema and venous

congestion in presacral area.

However, a post-operative MRI follow-up performed 6 months flowing discharge from the hospital revealed in 7 patients a lymphatic 'stipes-like' elements within the presacral adipose tissue with compression of the sacro-sciatic ligaments and bladder, all indicative of lymphatic alterations (figure 3). Moreover in 9 patients, the area of edema and venous congestion of pelvis together with compression of pelvic organs indicated by MRI signals, were located far from the area of surgical intervention (figure 4). Furthermore, in 8 patients, with the phase of T1 acquisition, epifascial "lakes" related to the muscular bands located outside of the pelvic floor in gluteal muscles were identified (figure 5). Additionally, in 6 patients, the DIT2 enabled the detection of moderate lymphatic stasis in the presacral space (figure 6). On the other hand, the 4 patients who underwent resection of the sigmoid colon and upper third of the rectum (without pelvic involvement due to intra-peritoneal adenocarcinoma located more than 12 cm from the anal verge), had a different MRI outcome. In details, the axial second planes were amplified with acquisition of T1, FST2 and DIT2- weighted sagittal and coronal images through subtraction of adipose tissue signals on the axial planes. Pre-operative MRI revealed no pelvic lymphedema or alterations of the pelvic lymphatics in these patients. Also the post-operative follow-up performed six months after discharge from the hospital, showed no evidence of pelvic wall edema. Two patients (number 1 and 4), submitted to resection of the sigmoid colon, presented mild signal intensification in the lower part of the rectal abdominal muscle (figure 7). Overall, there are no signs of lymphatic congestion anywhere within the pelvic wall were noted in the four patients with intra-peritoneal surgery.

Fig. 2. Phase of FST2 acquisition in pre-operative period, revealing no evidence of lymphedema. Arrows indicate the primary lesion.

However, a post-operative MRI follow-up performed 6 months flowing discharge from the hospital revealed in 7 patients a lymphatic 'stipes-like' elements within the presacral adipose tissue with compression of the sacro-sciatic ligaments and bladder, all indicative of lymphatic alterations (figure 3). Moreover in 9 patients, the area of edema and venous congestion of pelvis together with compression of pelvic organs indicated by MRI signals, were located far from the area of surgical intervention (figure 4). Furthermore, in 8 patients, with the phase of T1 acquisition, epifascial "lakes" related to the muscular bands located outside of the pelvic floor in gluteal muscles were identified (figure 5). Additionally, in 6 patients, the DIT2 enabled the detection of moderate lymphatic stasis in the presacral space (figure 6). On the other hand, the 4 patients who underwent resection of the sigmoid colon and upper third of the rectum (without pelvic involvement due to intra-peritoneal adenocarcinoma located more than 12 cm from the anal verge), had a different MRI outcome. In details, the axial second planes were amplified with acquisition of T1, FST2 and DIT2- weighted sagittal and coronal images through subtraction of adipose tissue signals on the axial planes. Pre-operative MRI revealed no pelvic lymphedema or alterations of the pelvic lymphatics in these patients. Also the post-operative follow-up performed six months after discharge from the hospital, showed no evidence of pelvic wall edema. Two patients (number 1 and 4), submitted to resection of the sigmoid colon, presented mild signal intensification in the lower part of the rectal abdominal muscle (figure 7). Overall, there are no signs of lymphatic congestion anywhere within the pelvic wall were noted in the four

Fig. 2. Phase of FST2 acquisition in pre-operative period, revealing no evidence of

lymphedema. Arrows indicate the primary lesion.

patients with intra-peritoneal surgery.

Fig. 3. Post-operative period. Phase of FST2 acquisition. White arrows indicate lymphangitis in the sacral area; large open arrow indicates presacral fibrosis.

Fig. 4. Post-operative period. Phase of FST2 acquisition. Note lymphedema and venous congestion in presacral area.

Pelvic Lymphedema in Rectal Cancer 99

Fig. 7. Post-operative period. Phase of FST2 acquisition. Arrows indicate mild

Pelvic cavity is a large region. The pelvic bone walls are completed with layered muscles: internal by pyriform and obturators, and closed in the bottom by levator ani and ischiococcygeal muscles which form the pelvic diaphragm or floor. In the pelvic cavity, like in the remaining abdominal cavity, peritoneum is separated from the walls which delimit the cavity by the extraperitoneal connective tissue. Peritoneum surrounds the organs contained in the pelvis is connected backwards with the extraperitoneal tissue, anteriorly with the connective tissue of the anterior compartment of the thigh through the obturator canals, laterally with that of the gluteal regions through the supra- and sub-pyriform canals of the great ischiatic foramen. The extraperitoneal connective tissue occupies the spaces free of viscera. In some points, such as around the rectum and bladder, it looks like a loose fatty connective tissue, while in others it gets thicker and forms septa and ligaments. These are, sometimes, provided with small bundles of smooth muscle cells which have the duty to support the pelvic viscera. These septa are the weak points of the whole pelvis. The septa, that can be hardly delimited from the adjacent loose tissue, surround the vessels directed to viscera or pelvic walls and are rich in lymphatic vessels and lymph nodes too (Wilting et al, 2004). It is, therefore, evident that any surgery in this area should be necessarily associated to a loss of potentially vital substance to perform a really radical lymphoadenectomy. The female pelvic cavity has a different aspect from the male cavity due to the particular development of the genital apparatus. While the male genital apparatus is hidden by the

hyperintensity in the area of abdominal rectal muscles.

**5. Discussion** 

**5.1 Pathophysiology of the pelvis** 

Fig. 5. Post-operative period. Phase of T1 acquisition. Arrows surrounding muscular fascia indicate the epifascial "lakes".

Fig. 6. Post-operative period. Phase of T2WI. Arrow indicates lymphedema in the presacral space.

Fig. 5. Post-operative period. Phase of T1 acquisition. Arrows surrounding muscular fascia

Fig. 6. Post-operative period. Phase of T2WI. Arrow indicates lymphedema in the presacral

indicate the epifascial "lakes".

space.

Fig. 7. Post-operative period. Phase of FST2 acquisition. Arrows indicate mild hyperintensity in the area of abdominal rectal muscles.

#### **5. Discussion**

#### **5.1 Pathophysiology of the pelvis**

Pelvic cavity is a large region. The pelvic bone walls are completed with layered muscles: internal by pyriform and obturators, and closed in the bottom by levator ani and ischiococcygeal muscles which form the pelvic diaphragm or floor. In the pelvic cavity, like in the remaining abdominal cavity, peritoneum is separated from the walls which delimit the cavity by the extraperitoneal connective tissue. Peritoneum surrounds the organs contained in the pelvis is connected backwards with the extraperitoneal tissue, anteriorly with the connective tissue of the anterior compartment of the thigh through the obturator canals, laterally with that of the gluteal regions through the supra- and sub-pyriform canals of the great ischiatic foramen. The extraperitoneal connective tissue occupies the spaces free of viscera. In some points, such as around the rectum and bladder, it looks like a loose fatty connective tissue, while in others it gets thicker and forms septa and ligaments. These are, sometimes, provided with small bundles of smooth muscle cells which have the duty to support the pelvic viscera. These septa are the weak points of the whole pelvis. The septa, that can be hardly delimited from the adjacent loose tissue, surround the vessels directed to viscera or pelvic walls and are rich in lymphatic vessels and lymph nodes too (Wilting et al, 2004). It is, therefore, evident that any surgery in this area should be necessarily associated to a loss of potentially vital substance to perform a really radical lymphoadenectomy. The female pelvic cavity has a different aspect from the male cavity due to the particular development of the genital apparatus. While the male genital apparatus is hidden by the

Pelvic Lymphedema in Rectal Cancer 101

Moreover, contrary to the remaining areas, these lymphatic pathways are exposed to a high pressure for two reasons: to counteract the pressure difference between endo-abdominal and endo-thoracic values and due to the calibre of the outflow vessels, which are particularly large (cisterna of Pecquet, lumbar right and left lymphatic trunks). The oncological surgery in the pelvic area always involves a remarkable radical operation of lymph nodes, which is partially necessary (lymphoadenectomy), but also unavoidable. The removal of extraperitoneal tissue occupying the areas free from viscera is, as mentioned above, abundantly supplied by lymphatic vessels. The lymphatic pathway on the transected area is completed removed without having any alternative outflow pathways (Taneja & Cady, 2005). It is appropriate to assume that the lymphedema related to lymphoadenectomy appears in the same way as it occurs in other body areas. However, due to its completely internal nature and its site within the bones of the pelvis, it cannot be immediately viewed during the inspection (Sallustio et al, 2000). Moreover, it is logic to presume that there is a histological picture related to the lymphedema which is comparable to that of other areas: interstitial retention of proteins, tissue inflammation, fatty tissue hypertrophy, fibrosis, progressive pathological condition (Warren et al, 2007). The progressive pathological condition should underlie the disease of the pelvic floor. As above mentioned, pelviperineology is a recent discipline and it is still subject to complex evaluations by many specialists: gynaecologists, urologists, proctologists, sexologists (Jones et al, 2008). The benefits resulting from the treatments of rehabilitation proposed by these specialists indirectly ensure the decongestive action typical for the physical exercise of the other body districts, beyond stimulating the correct recovery of the muscular activity. This should mean that the treatments of rehabilitation of pelvis result in the evident reduction in the edema and the related cohort of symptoms. Indeed, the best way to treat lymphedema and the related disorders seems to be the increase in the force of lymphatic circulation (Swartz et al, 2001). The filtration pressure in the tissue spaces ensures that lymph can move with force and this resulting liquid pressure in the tissue draws the blood from capillaries. The movement of the lymphatic valves provides to lymph the direction from the smaller lymphatic vessels into the lymphatic ducts. The automatic contraction of lymphatic vessels is one of the explanations of the lymphatic circulation and accelerates the formation of the lymph itself. The pressure resulting from the contraction of the adjacent muscles can compress the lymphatic vessels and push the lymphatic circulation towards the valves. It is easy to assume that a pelvic surgery irremediably impairs this fragile balance whereas the rehabilitation offered by the specialists studying the pelvic disorders produces a beneficial decompressing effect on the lymphedema, acting directly on the muscular structure. If this can explain the etiopathogenesis of lymphedema, it is not yet clear why the distribution of this disorder can be so variable. Some peculiar characteristics of the lymphatic vessels in the pelvic area need therefore to be considered. The normal function of the lymphatic vessels is to remove the portion of liquid leaked from the capillaries, which accumulates in the interstice, so that the interstitial pressure can be kept constant (Stachowska-Pietka et al, 2006). The venous capillaries reabsorb 90% of the liquid in the interstice, while the remaining fluid is transported to the blood by the lymphatic vessels in the form of lymph. Under normal conditions, the portion transported to the interstice is the same as that transported in the opposite direction. However, this balance is destroyed in the lymphoadenectomy due to the reduction in the lymph transport capacity. As a result, there is a liquid retention and swelling like in any other body organs after a lymphoadenectomy.

bladder, in the female uterus and its appendages acquire a considerable development: they rise from the extraperitoneal areal tissue and raise the serosa forming ligaments.

Uterus and ligaments, therefore, form a transversal septum which divides the pelvic cavity into an anterior portion, where bladder is sited, and a posterior one occupied by the rectum. Some lymphatic vessels of the rectal ampulla join at the root of the superior rectal vein to reach the anorectal and superior sacral lymph nodes, while others go up to the hypogastric lymph nodes. The bladder lymphatic vessels mouth into the hypogastric and external iliac lymph nodes.

In males the lymphatic vessels of the deferent canal and seminal vesicles are confluents of the external and internal iliac lymph nodes.

The prostate lymphatic vessels mouth into the hypogastric ones, while those of the anterior face of the prostate are confluents of anterior vesical lymph nodes or obturator lymph nodes. Regarding females, the lymphatic vessels of uterus are the following: the fundus uteri lymphatic vessels follow the ovarian vessels and are confluents to lumboaortic lymph nodes sited at the level of the renal hilus; some of the corpus and fundus uteri follow the round ligaments and reach inguinal lymph nodes, whereas those of the corpus and neck reach the internal iliac lymph nodes like those of vagina. In the pelvic extraperitoneal region lymphatic vessels follow the course of parietal and visceral veins and present lymph nodes alternating along their course.

Those distributed along the internal iliac vessels that receive lymphatic collectors of pelvic viscera and walls are particularly relevant. Finally, the pelvic cavity is externally closed by the perineum which is made by a diamond-shaped layer rich in fatty tissue. The most superficial lymphatic vessels are confluents of inguinal lymph nodes, while the internal ones go along the blood vessels and anastomose with the anal ones. The perineum in the posterior portion is crossed by anus whose lymphatic vessels which come from the columnar area and haemorrhoidal ring are confluents of internal iliac lymph nodes. The vessels of the anal orifice are confluents of the anorectal lymph nodes and inguinal lymph nodes of the medial group. The perineum in the anterior portion has a similar structure in both genders.

The constituting layers are, however, modified by the different conformation of the genital organs. In male two lymphatic pathways for the penis can be identified. The first consisting of superficial lymphatic vessels which join together in a unique trunk which flows with the dorsal superficial vein and mouths into the superficial inguinal lymph nodes and then bifurcates together with those coming from the scrotum. The second is constituted by deep lymphatic vessels which join in an unpaired dorsal trunk which goes with the anonymous vein and join the external iliac lymph nodes. The lymphatic vessels of testicle follow the spermatic cord and flow into lumboaortic lymph nodes. In the female, the lymphatic vessels of the mons of pubis, labia majora and minora are confluents of superficial inguinal lymph nodes. The lymphatic vessels of erectile organs are confluents of deep inguinal lymph nodes or external iliac vessels. It is evident how the pathways of lymphatic outflow of pelvis are extremely branched and the lymph node stations constitute a closely inter-connected complex.

bladder, in the female uterus and its appendages acquire a considerable development: they

Uterus and ligaments, therefore, form a transversal septum which divides the pelvic cavity into an anterior portion, where bladder is sited, and a posterior one occupied by the rectum. Some lymphatic vessels of the rectal ampulla join at the root of the superior rectal vein to reach the anorectal and superior sacral lymph nodes, while others go up to the hypogastric lymph nodes. The bladder lymphatic vessels mouth into the hypogastric and external iliac

In males the lymphatic vessels of the deferent canal and seminal vesicles are confluents of

The prostate lymphatic vessels mouth into the hypogastric ones, while those of the anterior face of the prostate are confluents of anterior vesical lymph nodes or obturator lymph nodes. Regarding females, the lymphatic vessels of uterus are the following: the fundus uteri lymphatic vessels follow the ovarian vessels and are confluents to lumboaortic lymph nodes sited at the level of the renal hilus; some of the corpus and fundus uteri follow the round ligaments and reach inguinal lymph nodes, whereas those of the corpus and neck reach the internal iliac lymph nodes like those of vagina. In the pelvic extraperitoneal region lymphatic vessels follow the course of parietal and visceral veins and present lymph nodes

Those distributed along the internal iliac vessels that receive lymphatic collectors of pelvic viscera and walls are particularly relevant. Finally, the pelvic cavity is externally closed by the perineum which is made by a diamond-shaped layer rich in fatty tissue. The most superficial lymphatic vessels are confluents of inguinal lymph nodes, while the internal ones go along the blood vessels and anastomose with the anal ones. The perineum in the posterior portion is crossed by anus whose lymphatic vessels which come from the columnar area and haemorrhoidal ring are confluents of internal iliac lymph nodes. The vessels of the anal orifice are confluents of the anorectal lymph nodes and inguinal lymph nodes of the medial group. The perineum in the anterior portion has a similar structure in

The constituting layers are, however, modified by the different conformation of the genital organs. In male two lymphatic pathways for the penis can be identified. The first consisting of superficial lymphatic vessels which join together in a unique trunk which flows with the dorsal superficial vein and mouths into the superficial inguinal lymph nodes and then bifurcates together with those coming from the scrotum. The second is constituted by deep lymphatic vessels which join in an unpaired dorsal trunk which goes with the anonymous vein and join the external iliac lymph nodes. The lymphatic vessels of testicle follow the spermatic cord and flow into lumboaortic lymph nodes. In the female, the lymphatic vessels of the mons of pubis, labia majora and minora are confluents of superficial inguinal lymph nodes. The lymphatic vessels of erectile organs are confluents of deep inguinal lymph nodes or external iliac vessels. It is evident how the pathways of lymphatic outflow of pelvis are extremely branched and the lymph node stations constitute a closely inter-connected

rise from the extraperitoneal areal tissue and raise the serosa forming ligaments.

lymph nodes.

both genders.

complex.

the external and internal iliac lymph nodes.

alternating along their course.

Moreover, contrary to the remaining areas, these lymphatic pathways are exposed to a high pressure for two reasons: to counteract the pressure difference between endo-abdominal and endo-thoracic values and due to the calibre of the outflow vessels, which are particularly large (cisterna of Pecquet, lumbar right and left lymphatic trunks). The oncological surgery in the pelvic area always involves a remarkable radical operation of lymph nodes, which is partially necessary (lymphoadenectomy), but also unavoidable. The removal of extraperitoneal tissue occupying the areas free from viscera is, as mentioned above, abundantly supplied by lymphatic vessels. The lymphatic pathway on the transected area is completed removed without having any alternative outflow pathways (Taneja & Cady, 2005). It is appropriate to assume that the lymphedema related to lymphoadenectomy appears in the same way as it occurs in other body areas. However, due to its completely internal nature and its site within the bones of the pelvis, it cannot be immediately viewed during the inspection (Sallustio et al, 2000). Moreover, it is logic to presume that there is a histological picture related to the lymphedema which is comparable to that of other areas: interstitial retention of proteins, tissue inflammation, fatty tissue hypertrophy, fibrosis, progressive pathological condition (Warren et al, 2007). The progressive pathological condition should underlie the disease of the pelvic floor. As above mentioned, pelviperineology is a recent discipline and it is still subject to complex evaluations by many specialists: gynaecologists, urologists, proctologists, sexologists (Jones et al, 2008). The benefits resulting from the treatments of rehabilitation proposed by these specialists indirectly ensure the decongestive action typical for the physical exercise of the other body districts, beyond stimulating the correct recovery of the muscular activity. This should mean that the treatments of rehabilitation of pelvis result in the evident reduction in the edema and the related cohort of symptoms. Indeed, the best way to treat lymphedema and the related disorders seems to be the increase in the force of lymphatic circulation (Swartz et al, 2001). The filtration pressure in the tissue spaces ensures that lymph can move with force and this resulting liquid pressure in the tissue draws the blood from capillaries. The movement of the lymphatic valves provides to lymph the direction from the smaller lymphatic vessels into the lymphatic ducts. The automatic contraction of lymphatic vessels is one of the explanations of the lymphatic circulation and accelerates the formation of the lymph itself. The pressure resulting from the contraction of the adjacent muscles can compress the lymphatic vessels and push the lymphatic circulation towards the valves. It is easy to assume that a pelvic surgery irremediably impairs this fragile balance whereas the rehabilitation offered by the specialists studying the pelvic disorders produces a beneficial decompressing effect on the lymphedema, acting directly on the muscular structure. If this can explain the etiopathogenesis of lymphedema, it is not yet clear why the distribution of this disorder can be so variable. Some peculiar characteristics of the lymphatic vessels in the pelvic area need therefore to be considered. The normal function of the lymphatic vessels is to remove the portion of liquid leaked from the capillaries, which accumulates in the interstice, so that the interstitial pressure can be kept constant (Stachowska-Pietka et al, 2006). The venous capillaries reabsorb 90% of the liquid in the interstice, while the remaining fluid is transported to the blood by the lymphatic vessels in the form of lymph. Under normal conditions, the portion transported to the interstice is the same as that transported in the opposite direction. However, this balance is destroyed in the lymphoadenectomy due to the reduction in the lymph transport capacity. As a result, there is a liquid retention and swelling like in any other body organs after a lymphoadenectomy.

Pelvic Lymphedema in Rectal Cancer 103

In this pilot study using abdominal MRI we hypothesized that pelvic surgery, regardless of the extra-peritoneal organs, results in the loss of continuity of the pelvic region as key event with the following reduction in fatty extra-peritoneal tissue where the lymph node stations are mostly concentrated; the consequent pelvic lymphadenectomy, should be followed by a pelvic lymphedema (Vannelli et al, 2009). As lymphedema been discovered often by chance and has no reported common elements, it has been difficult to create an experimental model (Savoye-Collet et al, 2008). Here, we attempted to generate a diagnostic model by exploiting

Lymphedema results from an alteration of lymphatic vessels as a consequence of malformation (primary) or mechanical damage (secondary) (Warren et al, 2007), consistent with an equal distribution in the upper and lower limbs, neck, scrotum and pubis (Purushotham et al, 2007; Fang et al 2008). Analogously, pelvic lymphedema might be a consequence of mechanical pelvic injury or of the altered lymphatic system caused by such injury. The extra-peritoneal pelvic area is sited between the peritoneum covering the pelvic organs, and the pelvic diaphragm. In the pelvic cavity the peritoneum is separated from the walls which delimit the cavity by the surrounding and supporting fatty extra-peritoneal tissue. Pelvic lymphadenectomy might in itself lead to damaged lymphatic vessels with subsequent pelvic malfunction, within a few weeks post surgery if undiagnosed and untreated, can progress to a chronic pelvic dysfunction. Our post-operative MRIs evidenced injuries involving different pelvic structures and areas, whereas no venous congestion or alteration of lymphatic vessels was detected preoperatively (Table II). Therefore it is of critical importance to investigate the mechanisms of lymphedema in pelvic pathology to limit the consequences of functional abnormalities in patients who undergo conservative surgery. Thus, despite the benefits of surgery, our results support the notion that lymphadenectomy can cause damage of the pelvic lymphatic system as a direct result of surgery. Unlike the common clinical skin signs that characterized all other sites of lymphedema, pelvic lymphedema is "hidden" or silent, with no skin changes or any single symptom manifested (Vannelli et al, 2009). The lack of signs is not surprising, considering that the shell structure of bones of the sacral area provides a structural system capable of containing almost three-fourths of the total volume alterations inside the pelvis without any external manifestations. Moreover, the perineum, which contains no bone structures and thus enables direct and unrestricted internal pelvic communication, is particularly vulnerable to damage caused by lymphadenectomy. This alteration of lymphatic vessels would produce lymphedema or progressive dysfunctional pathology manifesting as muscular deficiency, particularly defective sphincter control. As shown in our MRIs of the bone-tendineal space interposed within a deep plane of the pelvic floor, surgical intervention involving perineal skin "hidden" (Figure 5,6) lymphedema, despite the lymphatic congestion after lymphadenectomy and eventually the conditions for neural and muscular structural malfunction (Handa et al, 2009). In this series, the use of MRI has made it possible to emphasize the pre-operative period in which the presence of the cancer is not associated with any pelvic lymphedema. Moreover, our MRIs showed that pelvic illness alone is accompanied by lymphedema related exclusively to venous congestion, which can be attributed to the neoangiogenesis typically concurrent in these carcinomas. In the postoperative period the effects of lymphadenectomy and opening of the pelvic peritoneum are

**5.2 Clinical evidence of pelvic lymphedema** 

the radiological resources available in our laboratory.

Moreover, the pelvic lymphatic vessels serve to remove macromolecules, such as proteins, from interstice. Unlike other anatomical regions, the particular structure of the pelvis with its parallelepipid shape and semirigid shell, the abundant distribution of venous plexus as well as the tight bond with the intestinal lymphatic tissue make the role of the lymphatic vessels even more specific (Barret et al, 2006). When the proteins diffuse through the arterial capillary wall, they are downgraded by the macrophages, which allow them to come back to the blood circulation through the venous capillary circulation, or are reabsorbed through the lymphatic vessels (Greitz, 2002). During pelvic surgery it is easy to assume that the resulting inflammatory picture will be so widespread that a remarkable number of macrophages will be recruited through the activation of different cell lines and partially contrast the effect of the resulting lymphedema. Moreover, in case of obstructed, abnormal or absent lymphatic system, a lymphatic stasis can occur, leading to retention of proteins and liquid in the interstice. Another element contributes to counteract this effect, namely the close inter-connection with the venous plexus present in the pelvis micro-circulation which acts by mimicking the role of the lymphatic vessels. According to the classical theory, this increase in protein concentration leads to an increase in the tissue colloido–osmotic pressure, which draws liquids into the interstice and causes edema and clinical outbreaks of lymphedema. On the other hand, the intra-abdominal pressure, which ranges from 3 to 5 mm Hg in the postoperative period, contributes to strengthen the effect of lymphedema. Although the intra-abdominal pressure is distributed on the whole cavity, it leads to a higher effect of venous stasis in the operated pelvis, adding to lymphatic pressure. The clinical occurrences of lymphedema occur following the retention of edematogenic liquid in the fatty and subcutaneous tissue. The inflammatory response appears with the liquid retention in the interstitial space. In addition to the inflammation, the slowed lymphatic flow is also associated to an increase in the lipogenesis and fat deposition, to the increase in the activation of fibrocytes and expansion of connective tissue. The patient would progressively develop a subcutaneous hard tissue as a result of the consequent fibrosis in addition to hypertrophy of the fatty tissue. These pathological changes will initially develop as simple swelling, but later on their persistence would lead to a higher state of hardening. Unlike the other regions, the performance of an intra-abdominal surgery, with no contact with the external environment, will never cause the classical signs which are normally visible in another body region. In these terms, it is less difficult to suggest a pelvic lymphedema. Pelvis is a functional unit, therefore, after a surgery (conservative or radical, with or without post-operative treatment); the patients develop pelvic dysfunctions, probably due to lymphedema. We believe that this disorder without an appropriate rehabilitation leads to an inflammation with interstitial liquid retention with high protein concentration, which results in fatty tissue hypertrophy and fibrosis, and develops as a progressive pathological condition. We can therefore agree with the hypothesis that the lymphatic damage leads to pathology of progressive malfunctioning that, if not properly treated, can become chronic within few weeks and result in a severe chronic disease. The pelvic lymphedema can be a difficult condition to be treated and one of those causes with significant morbility for the patient both from the clinical and psychological points of view. The clinical evidence shows that the lymphatic vessels play a relevant role in the pathology of the pelvic floor and perineum.

Moreover, the pelvic lymphatic vessels serve to remove macromolecules, such as proteins, from interstice. Unlike other anatomical regions, the particular structure of the pelvis with its parallelepipid shape and semirigid shell, the abundant distribution of venous plexus as well as the tight bond with the intestinal lymphatic tissue make the role of the lymphatic vessels even more specific (Barret et al, 2006). When the proteins diffuse through the arterial capillary wall, they are downgraded by the macrophages, which allow them to come back to the blood circulation through the venous capillary circulation, or are reabsorbed through the lymphatic vessels (Greitz, 2002). During pelvic surgery it is easy to assume that the resulting inflammatory picture will be so widespread that a remarkable number of macrophages will be recruited through the activation of different cell lines and partially contrast the effect of the resulting lymphedema. Moreover, in case of obstructed, abnormal or absent lymphatic system, a lymphatic stasis can occur, leading to retention of proteins and liquid in the interstice. Another element contributes to counteract this effect, namely the close inter-connection with the venous plexus present in the pelvis micro-circulation which acts by mimicking the role of the lymphatic vessels. According to the classical theory, this increase in protein concentration leads to an increase in the tissue colloido–osmotic pressure, which draws liquids into the interstice and causes edema and clinical outbreaks of lymphedema. On the other hand, the intra-abdominal pressure, which ranges from 3 to 5 mm Hg in the postoperative period, contributes to strengthen the effect of lymphedema. Although the intra-abdominal pressure is distributed on the whole cavity, it leads to a higher effect of venous stasis in the operated pelvis, adding to lymphatic pressure. The clinical occurrences of lymphedema occur following the retention of edematogenic liquid in the fatty and subcutaneous tissue. The inflammatory response appears with the liquid retention in the interstitial space. In addition to the inflammation, the slowed lymphatic flow is also associated to an increase in the lipogenesis and fat deposition, to the increase in the activation of fibrocytes and expansion of connective tissue. The patient would progressively develop a subcutaneous hard tissue as a result of the consequent fibrosis in addition to hypertrophy of the fatty tissue. These pathological changes will initially develop as simple swelling, but later on their persistence would lead to a higher state of hardening. Unlike the other regions, the performance of an intra-abdominal surgery, with no contact with the external environment, will never cause the classical signs which are normally visible in another body region. In these terms, it is less difficult to suggest a pelvic lymphedema. Pelvis is a functional unit, therefore, after a surgery (conservative or radical, with or without post-operative treatment); the patients develop pelvic dysfunctions, probably due to lymphedema. We believe that this disorder without an appropriate rehabilitation leads to an inflammation with interstitial liquid retention with high protein concentration, which results in fatty tissue hypertrophy and fibrosis, and develops as a progressive pathological condition. We can therefore agree with the hypothesis that the lymphatic damage leads to pathology of progressive malfunctioning that, if not properly treated, can become chronic within few weeks and result in a severe chronic disease. The pelvic lymphedema can be a difficult condition to be treated and one of those causes with significant morbility for the patient both from the clinical and psychological points of view. The clinical evidence shows that the lymphatic vessels play

a relevant role in the pathology of the pelvic floor and perineum.

#### **5.2 Clinical evidence of pelvic lymphedema**

In this pilot study using abdominal MRI we hypothesized that pelvic surgery, regardless of the extra-peritoneal organs, results in the loss of continuity of the pelvic region as key event with the following reduction in fatty extra-peritoneal tissue where the lymph node stations are mostly concentrated; the consequent pelvic lymphadenectomy, should be followed by a pelvic lymphedema (Vannelli et al, 2009). As lymphedema been discovered often by chance and has no reported common elements, it has been difficult to create an experimental model (Savoye-Collet et al, 2008). Here, we attempted to generate a diagnostic model by exploiting the radiological resources available in our laboratory.

Lymphedema results from an alteration of lymphatic vessels as a consequence of malformation (primary) or mechanical damage (secondary) (Warren et al, 2007), consistent with an equal distribution in the upper and lower limbs, neck, scrotum and pubis (Purushotham et al, 2007; Fang et al 2008). Analogously, pelvic lymphedema might be a consequence of mechanical pelvic injury or of the altered lymphatic system caused by such injury. The extra-peritoneal pelvic area is sited between the peritoneum covering the pelvic organs, and the pelvic diaphragm. In the pelvic cavity the peritoneum is separated from the walls which delimit the cavity by the surrounding and supporting fatty extra-peritoneal tissue. Pelvic lymphadenectomy might in itself lead to damaged lymphatic vessels with subsequent pelvic malfunction, within a few weeks post surgery if undiagnosed and untreated, can progress to a chronic pelvic dysfunction. Our post-operative MRIs evidenced injuries involving different pelvic structures and areas, whereas no venous congestion or alteration of lymphatic vessels was detected preoperatively (Table II). Therefore it is of critical importance to investigate the mechanisms of lymphedema in pelvic pathology to limit the consequences of functional abnormalities in patients who undergo conservative surgery. Thus, despite the benefits of surgery, our results support the notion that lymphadenectomy can cause damage of the pelvic lymphatic system as a direct result of surgery. Unlike the common clinical skin signs that characterized all other sites of lymphedema, pelvic lymphedema is "hidden" or silent, with no skin changes or any single symptom manifested (Vannelli et al, 2009). The lack of signs is not surprising, considering that the shell structure of bones of the sacral area provides a structural system capable of containing almost three-fourths of the total volume alterations inside the pelvis without any external manifestations. Moreover, the perineum, which contains no bone structures and thus enables direct and unrestricted internal pelvic communication, is particularly vulnerable to damage caused by lymphadenectomy. This alteration of lymphatic vessels would produce lymphedema or progressive dysfunctional pathology manifesting as muscular deficiency, particularly defective sphincter control. As shown in our MRIs of the bone-tendineal space interposed within a deep plane of the pelvic floor, surgical intervention involving perineal skin "hidden" (Figure 5,6) lymphedema, despite the lymphatic congestion after lymphadenectomy and eventually the conditions for neural and muscular structural malfunction (Handa et al, 2009). In this series, the use of MRI has made it possible to emphasize the pre-operative period in which the presence of the cancer is not associated with any pelvic lymphedema. Moreover, our MRIs showed that pelvic illness alone is accompanied by lymphedema related exclusively to venous congestion, which can be attributed to the neoangiogenesis typically concurrent in these carcinomas. In the postoperative period the effects of lymphadenectomy and opening of the pelvic peritoneum are

Pelvic Lymphedema in Rectal Cancer 105

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**8. References** 

characterized by specific signs of lymphedema, such as lymphangitis with local fibrosis formation. Actually, the identification of epifascial "lakes" over gluteus muscles in the absence of edema inside of the muscular girdles demonstrates that surgical intervention sets off a domino effect within the pelvic area. The observed venous congestion in areas distant from the interventional area both in patients surgically treated with opening of the extra-peritoneal space and in those without pelvic involvement, further confirms an alteration of pelvic structures following pelvic surgery. Our series of MRIs also identified other common features of lymphedema: accumulation of liquid in adipose tissue or lipedema. The estimate of body fat indicate an average BMI of 29.9 (so called overweight), since reduction of adipose tissue, where lymph nodes are predominantly concentrated, might contribute to the loss of pelvic structural continuity. Moreover, the specific structure of pelvic lymphatics must be considered, since it is ubiquitously and homogenously distributed as a thick net and conveys a "three-dimensional" appearance of volume, unlike the generally single long dimension that characterizes the upper or lower limb lymphatics. Surgery leads not only to the limitation of volume, but also to the involvement of all pelvic structures. To date, lymphedema is frequently undiagnosed even in teaching centers (Schuchhardt C, 1997), and it seems likely that many surgical interventions have not been adequately studied with respect to lymphatic damage and their consequences. Although it could be argued that such studies are not essential when colorectal surgery is only limited to an internal pelvic space, and that any radiological image is only one indictor of type of surgical intervention, we detected signs of venous congestion in all pelvic areas, demonstrating that each surgical procedure implicates involvement of the entire pelvic structure. Thus, it is not the type of surgical intervention that creates favourable conditions for lymphedema, but rather the specific location of the pelvic floor where surgery occurs. The pelvis is a dynamic functional unit endowed with an elastic memory continually responding to changes of: body weight, intra-abdominal pressure due to increased loads caused by chronic conditions, and by the natural events of pregnancy and delivery. Elastic memory of the pelvis contributes in inhibiting the onset of lymphedema. However, surgical disruption of this functional unit, in particular impairment of the pelvic memory capability is exceeded can lead to hides lymphedema. Overall this can be the key factor in explaining pelvic dysfunction.

#### **6. Conclusion**

Clinical evidence obtained by MRI in our pilot study indicates that lymphatic vessels play a significant role in surgeries that involve perineum and the pelvic floor (Boekhuis et al, 2009; Campisi, 1991). This pilot study could answer the question ''how does pelvic lymphedema occur?". During surgery the primary cause responsible for the damage should be detected otherwise if, not promptly treated, it can result in a chronic disease. However a better understanding of pelvic lymphedema could be the key to improving therapeutic strategies, including the routine use of biofeedback re-education of the pelvic floor, for functional abnormalities after pelvic surgery (Striefel & Glazer, 2008).

#### **7. Acknowledgments**

The authors thank Dr Patrizia Gasparini who helped write and revise the paper and Mrs. Roberta Aceto for her assistance with data collection.

#### **8. References**

104 Novel Strategies in Lymphedema

characterized by specific signs of lymphedema, such as lymphangitis with local fibrosis formation. Actually, the identification of epifascial "lakes" over gluteus muscles in the absence of edema inside of the muscular girdles demonstrates that surgical intervention sets off a domino effect within the pelvic area. The observed venous congestion in areas distant from the interventional area both in patients surgically treated with opening of the extra-peritoneal space and in those without pelvic involvement, further confirms an alteration of pelvic structures following pelvic surgery. Our series of MRIs also identified other common features of lymphedema: accumulation of liquid in adipose tissue or lipedema. The estimate of body fat indicate an average BMI of 29.9 (so called overweight), since reduction of adipose tissue, where lymph nodes are predominantly concentrated, might contribute to the loss of pelvic structural continuity. Moreover, the specific structure of pelvic lymphatics must be considered, since it is ubiquitously and homogenously distributed as a thick net and conveys a "three-dimensional" appearance of volume, unlike the generally single long dimension that characterizes the upper or lower limb lymphatics. Surgery leads not only to the limitation of volume, but also to the involvement of all pelvic structures. To date, lymphedema is frequently undiagnosed even in teaching centers (Schuchhardt C, 1997), and it seems likely that many surgical interventions have not been adequately studied with respect to lymphatic damage and their consequences. Although it could be argued that such studies are not essential when colorectal surgery is only limited to an internal pelvic space, and that any radiological image is only one indictor of type of surgical intervention, we detected signs of venous congestion in all pelvic areas, demonstrating that each surgical procedure implicates involvement of the entire pelvic structure. Thus, it is not the type of surgical intervention that creates favourable conditions for lymphedema, but rather the specific location of the pelvic floor where surgery occurs. The pelvis is a dynamic functional unit endowed with an elastic memory continually responding to changes of: body weight, intra-abdominal pressure due to increased loads caused by chronic conditions, and by the natural events of pregnancy and delivery. Elastic memory of the pelvis contributes in inhibiting the onset of lymphedema. However, surgical disruption of this functional unit, in particular impairment of the pelvic memory capability is exceeded can lead to hides lymphedema.

Overall this can be the key factor in explaining pelvic dysfunction.

abnormalities after pelvic surgery (Striefel & Glazer, 2008).

Roberta Aceto for her assistance with data collection.

Clinical evidence obtained by MRI in our pilot study indicates that lymphatic vessels play a significant role in surgeries that involve perineum and the pelvic floor (Boekhuis et al, 2009; Campisi, 1991). This pilot study could answer the question ''how does pelvic lymphedema occur?". During surgery the primary cause responsible for the damage should be detected otherwise if, not promptly treated, it can result in a chronic disease. However a better understanding of pelvic lymphedema could be the key to improving therapeutic strategies, including the routine use of biofeedback re-education of the pelvic floor, for functional

The authors thank Dr Patrizia Gasparini who helped write and revise the paper and Mrs.

**6. Conclusion** 

**7. Acknowledgments** 


Pelvic Lymphedema in Rectal Cancer 107

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### *Edited by Alberto Vannelli*

Lymphedema is a swelling caused by the abnormal accumulation of lymphatic fluid in the skin. Lymphedema can be caused by burns, injury, surgery, radiation therapy or cancer treatment that cancer survivors undergo. Risk of developing lymphedema is high especially in those with breast or prostate cancer. It is hereditary and can appear without warning at any time of life and is related to obesity and circulatory problems. If not treated, lymphedema can be painful and lead to life-threatening infections. This book will help physicians who deal with lymphedema. It will help you understand how the lymphatic system works, how lymphedema is diagnosed, how to cope with the challenges of lymphedema, how to find treatment, and how to deal with insurance issues. Novel Strategies in Lymphedema is for those with, or at risk of, developing lymphedema, and the healthcare professionals who care for them.

Novel Strategies in Lymphedema

Novel Strategies in

Lymphedema

*Edited by Alberto Vannelli*

Photo by defun / iStock