**6. Pancreatic metastases from melanomas**

Pancreatic metastases from melanomas are rare situations, only few such cases being presented so far; moreover, most often the cases are presented as case reports or small case series involving less than 10 cases, a standard therapeutic protocol being hard to be established. Up to half of patients presenting with pancreatic metastases from melanomas present in fact disseminated metastatic lesions in the context of the systemic recurrence, being associated with an extremely poor prognostic. Less than 2% of patients with pancreatic metastases from melanomas will be diagnosed with oligometastatic disease, most often the primary tumor being an ocular melanoma [30, 31].

As for the long-term outcomes, patients presenting pancreatic metastases originating from melanomas with various locations seem to have a poorer prognostic when compared to other primaries due to the aggressive biological behavior of melanomas [19]. However, compared to patients treated in a conservative manner, it seems that patients submitted to surgery might benefit from a better outcome especially in cases in which complete resection of the pancreatic lesion is feasible [32, 33]. When it comes to the most important prognostic factors which might influence the long-term outcomes, it seems that a long disease free survival interval is usually associated with a lower biological aggressivity of the primary tumor, and, therefore, with a better outcome [34].

In a case series of two patients diagnosed with pancreatic metastases from melanomas at *Melbourne University*, *Austin Hospital*, *Victoria*, *Australia* published in 2003, the authors reported encouraging results; the first case was the one of a 45-year-old woman with personal history of ocular melanoma treated by transscleral resection 12 years earlier, the histopathological studies revealing at that moment a 10 mm mixed spindle and epithelioid cell melanoma; however, she experienced an early local recurrence 1 year postoperatively, laser therapy being performed at the time of relapse. About 11 years later (after the first local relapse), the patient was diagnosed with a pancreatic head tumor in association with three to four well defined hepatic nodules measuring 5–10 mm, while the fine needle biopsy confirmed the metastatic character of the tumor originating from the melanoma. The patient was submitted to a pylorus preserving pancreatoduodenectomy and segmental liver resection, the histopathological studies confirming the metastatic character of all the resected tumors. The patient was free of disease at 6 months follow-up. The second reported case from the same authors was the one of a 55-year-old patient known with a previous history of ocular melanoma enucleated 13 years earlier who complained of epigastric pain and was diagnosed with a tumoral mass at the level of the pancreatic head; intraoperatively multiple pigmented lesions were seen on the whole surface of the pancreas, so the patient was submitted to total pancreatectomy and remained free of disease 7 months later [34].

Wood's series conducted on a group of six patients with pancreatic metastases forming melanomas, complete surgical resection of the pancreatic lesion was associated with a median overall survival rate of 24 months, significantly higher than the survival rates after palliative chemotherapy (where the median overall survival rate does not surpass 12 months) [35, 36]. However, in Woods' study one of the most important prognostic factors was related to the resection margins, patients presenting with positive resection margins or incomplete resection being associated with a significantly poorer outcome (in fact in these cases the median survival rate was 8 months, similar to the one reported after palliative chemotherapy) [35]. In conclusion incomplete resection has no benefit in terms of survival.

## **7. Pancreatic metastases from breast cancer**

**5. Pancreatic metastases from colorectal cancer**

up to half per cent of cases [6].

**Name, year of the study**

138 Advances in Pancreatic Cancer

Sohn, 2001 [27]

pancreatectomy.

**Period of the study**

1989– 1999

**No. of patients** **Disease free interval**

10 patients 9.8 years PD: 7 cases

**Table 1.** Outcomes after pancreatic resections for pancreatic metastases from renal cell carcinomas.

**6. Pancreatic metastases from melanomas**

Colorectal cancer represents one of the most common reported malignancies worldwide, being the third cause of death following breast and lung cancer and the second cause of death among non-smokers [28]. When it comes to the most common patterns of spread in colorectal cancers, they are represented by the peritoneal, lymphatic and hematogenous spread; the hematogenous route is usually related to the apparition of parenchymatous lesions located in liver, lung or brain. In certain cases, pancreatic metastases from colorectal malignancies can occur, the estimated incidence being of 2%; these types of lesions are usually associated with peritoneal carcinomatosis and less often as single lesions [29]. When it comes to the most appropriate imagistic study in order to confirm the presence of such lesions, CT has been proposed, followed by PET-CT (in cases in which although the clinical symptoms are highly suggestive for a pancreatic lesion but standard CT failed to diagnose it). It has been reported that PET-CT is a highly sensitive method of diagnostic in such cases (with an estimated sensitivity of 90–95%) while the specificity ranges between 65 and 85%; therefore performing a PET-CT in such cases seems to be responsible for the change of the therapeutic approach in

**Type of pancreatic resection**

DP: 2 cases TP: 1 cases

*Abbreviations*: DP, distal pancreatectomy; PD, pancreatoduodenectomy; TP, total pancreatectomy; MP, middle

**Early postoperative** 

**Long-term outcomes**

75%

Overall survival after pancreatic resections at 5 year follow-up:

**outcomes**

Postoperative mortality: 0

Isolated pancreatic metastases from colorectal cancer suitable for resections are scarce eventualities, only few cases being reported so far. Therefore is difficult to establish whether surgical resections of such lesions is superior to the conservative treatment such chemotherapy, due to the small number of cases submitted to surgery. However, it seems that surgery is especially useful in patients with symptomatic lesions, a satisfactory symptom relief being reported [10].

Pancreatic metastases from melanomas are rare situations, only few such cases being presented so far; moreover, most often the cases are presented as case reports or small case series involving less than 10 cases, a standard therapeutic protocol being hard to be established. Up to half of patients presenting with pancreatic metastases from melanomas present in fact disseminated metastatic lesions in the context of the systemic recurrence, being associated

Intra-abdominal breast cancer metastases are usually diagnosed at the level of the liver, spleen or axial skeleton [37]. When reported, pancreatic metastases from breast cancer are usually associated with other disseminated lesions. Oligometastatic disease has been rarely diagnosed; however, these kinds of lesions might be seen after a long disease free survival interval; therefore, the diagnostic of metastatic disease should be kept in mind whenever a pancreatic tumor is diagnosed in a patient with previous history of breast cancer [38, 39]. In such cases, the clinical signs and symptoms can range from totally asymptomatic lesions to diffuse upper abdominal pain, jaundice or acute pancreatitis due to the concomitant obstruction of the common bile duct or of the Wirsung duct [38, 39].

were included. These patients were divided in 3 groups according to the time when the surgical procedure was performed: there were 57 patients submitted to surgery after the date of May 2000 when extensive upper abdominal resections were performed as part of debulking surgery. Groups 2 and 3 were submitted to surgery before that date and included 122 patients submitted to cytoreductive surgery for pelvic confined disease (group 2) and 83 patients, respectively, submitted to debulking surgery for extensive lesions (group 3); therefore, most patients in the third group were suboptimally cytoreduced due to the extension of the tumoral process in the upper abdomen. The authors demonstrated a median progression free survival of 24, 23 and 11 months, respectively, for groups 1, 2 and 3. Moreover the author reported a median overall survival of 84 months for group number 2, 28 months for group number 3 and was not reached by the end of the study for group number 1. In conclusion, the authors underlined that the long-term outcomes were not influenced by the extension of the upper abdominal resections as part of debulking surgery, the only factor which strongly shortened survival being the presence of residual disease [43]. Therefore the upper abdominal resections were successfully included as part of debulking surgery for both advanced

Pancreatic Resections for Metastatic Disease http://dx.doi.org/10.5772/intechopen.75571 141

Pancreatic metastases from ovarian cancer usually develop as part of systemic dissemination of the malignant process, the main patterns of spread including peritoneal, hematogenous or lymphatic spread. When it comes to the pancreatic involvement due to ovarian cancer, the

When it comes to the association of pancreatic surgery as part of debulking surgery for advanced stage or relapsed ovarian cancer, it has been initially considered that association of such procedures will lead to the apparition of an unacceptable risk of perioperative complications. However, a study conducted by Kehoe et al. demonstrated that these surgical procedures can be successfully associated as part of debulking surgery. The authors reported a series of 17 patients submitted to distal pancreatectomies for pancreatic metastases with ovarian origin, the median age of patients being of 63 years. When it comes to the surgical outcomes, nine patients were submitted to debulking surgery to no residual disease, seven cases were submitted to optimal cytoreductive surgery while in one case a suboptimal cytoreductive surgery was performed; however, in this last case the presence of tumoral residual lesions was described at the level of the diaphragm and in the liver. When it comes to the short-term outcomes, the authors reported a morbidity rate of 24%, all patients being diagnosed with pancreatic fistulas. However, the presence of pancreatic fistulas did not impede the administration of the adjuvant therapy. Moreover, the rate of pancreatic leaks was similar to the one reported by surgeons performing pancreatic resections for pancreatic primaries, demonstrating in this way that pancreatic surgery can be safely associated as part of debulking surgery

When it comes to the long-term outcomes after pancreatic resections for advanced stage or recurrent ovarian cancer, an interesting study was conducted in *Fundeni Clinical Hospital, Bucharest, Romania,* and was conducted by Bacalbasa et al. The study included one patient submitted to pancreatic resections as part of primary cytoreduction, four cases submitted to surgery as part of secondary cytoreduction and one case submitted to pancreatic resection

most commonly involved mechanisms include peritoneal and hematogenous spread.

and recurrent ovarian cancer.

for advanced stage or recurrent ovarian cancer [44].

Pancreatic metastases from breast cancer have been reported with an incidence of 13% in autopsy studies and are usually associated with other disseminated lesions, transforming the patient into a candidate for a palliative oncologic treatment [40]. However, in cases presenting as oligometastatic lesions, surgery has been proposed, this therapeutic approach being encouraged by the success reported by hepatobiliary surgeons who performed surgery for isolated hepatic metastatic with mammary origin [41].

Bednar et al. reported a case series of two patients diagnosed with pancreatic metastases from breast cancer origin. The first one was the case of a 75-year-old patient diagnosed with an invasive lobular breast carcinoma at 58 years of age for which she was submitted to a radical mastectomy at that moment, followed by adjuvant hormonal therapy based on tamoxifen. About 18 years later, the patient was investigated for weight loss, jaundice and she was diagnosed with a pancreatic head tumor; she was resubmitted to surgery, a pancreatoduodenectomy being performed. The histopathological studies confirmed the presence of a metastatic lesion originating from the primary breast cancer; postoperatively, she was resubmitted to hormonal treatment. At 4 year follow-up, the patient was alive with disease, disseminated metastatic lesions in the contralateral axilla being found. The second case was the one of a 57-year-old patient initially diagnosed with stage IIA mixed cellularity Hodgkin's lymphoma initially treated by radiotherapy, which developed 19 years after breast tumor. At that moment the patient was submitted to surgery, the histopathological studies demonstrating the presence of a high grade phyllodes tumor. About 4 years later, the patient was diagnosed with a pancreatic head tumor, in association with lung nodules which were biopsied, the histopathological studies confirming the metastatic character originating from the phyllodes tumor. Therefore the patient was submitted to palliative chemotherapy and died 15 months later [42].

#### **8. Pancreatic metastases from ovarian cancer**

Ovarian cancer remains one of the most aggressive gynecological malignancies due to the fact that most often patients are diagnosed in advanced stages of disease, when disseminated lesions are already present. In such cases, the principles of debulking surgery were successfully applied especially for pelvic confined disease. However, patients presenting extended upper abdominal lesions were considered to a have a poorer outcome due to a more aggressive surgical biology. This myth was destroyed by the first studies which incorporated extended upper abdominal resections as part of debulking surgery; in Eisenhauer's study conducted between 1998 and 2003, 262 patients with advanced stage ovarian cancer were included. These patients were divided in 3 groups according to the time when the surgical procedure was performed: there were 57 patients submitted to surgery after the date of May 2000 when extensive upper abdominal resections were performed as part of debulking surgery. Groups 2 and 3 were submitted to surgery before that date and included 122 patients submitted to cytoreductive surgery for pelvic confined disease (group 2) and 83 patients, respectively, submitted to debulking surgery for extensive lesions (group 3); therefore, most patients in the third group were suboptimally cytoreduced due to the extension of the tumoral process in the upper abdomen. The authors demonstrated a median progression free survival of 24, 23 and 11 months, respectively, for groups 1, 2 and 3. Moreover the author reported a median overall survival of 84 months for group number 2, 28 months for group number 3 and was not reached by the end of the study for group number 1. In conclusion, the authors underlined that the long-term outcomes were not influenced by the extension of the upper abdominal resections as part of debulking surgery, the only factor which strongly shortened survival being the presence of residual disease [43]. Therefore the upper abdominal resections were successfully included as part of debulking surgery for both advanced and recurrent ovarian cancer.

usually associated with other disseminated lesions. Oligometastatic disease has been rarely diagnosed; however, these kinds of lesions might be seen after a long disease free survival interval; therefore, the diagnostic of metastatic disease should be kept in mind whenever a pancreatic tumor is diagnosed in a patient with previous history of breast cancer [38, 39]. In such cases, the clinical signs and symptoms can range from totally asymptomatic lesions to diffuse upper abdominal pain, jaundice or acute pancreatitis due to the concomitant obstruc-

Pancreatic metastases from breast cancer have been reported with an incidence of 13% in autopsy studies and are usually associated with other disseminated lesions, transforming the patient into a candidate for a palliative oncologic treatment [40]. However, in cases presenting as oligometastatic lesions, surgery has been proposed, this therapeutic approach being encouraged by the success reported by hepatobiliary surgeons who performed surgery for

Bednar et al. reported a case series of two patients diagnosed with pancreatic metastases from breast cancer origin. The first one was the case of a 75-year-old patient diagnosed with an invasive lobular breast carcinoma at 58 years of age for which she was submitted to a radical mastectomy at that moment, followed by adjuvant hormonal therapy based on tamoxifen. About 18 years later, the patient was investigated for weight loss, jaundice and she was diagnosed with a pancreatic head tumor; she was resubmitted to surgery, a pancreatoduodenectomy being performed. The histopathological studies confirmed the presence of a metastatic lesion originating from the primary breast cancer; postoperatively, she was resubmitted to hormonal treatment. At 4 year follow-up, the patient was alive with disease, disseminated metastatic lesions in the contralateral axilla being found. The second case was the one of a 57-year-old patient initially diagnosed with stage IIA mixed cellularity Hodgkin's lymphoma initially treated by radiotherapy, which developed 19 years after breast tumor. At that moment the patient was submitted to surgery, the histopathological studies demonstrating the presence of a high grade phyllodes tumor. About 4 years later, the patient was diagnosed with a pancreatic head tumor, in association with lung nodules which were biopsied, the histopathological studies confirming the metastatic character originating from the phyllodes tumor. Therefore

the patient was submitted to palliative chemotherapy and died 15 months later [42].

Ovarian cancer remains one of the most aggressive gynecological malignancies due to the fact that most often patients are diagnosed in advanced stages of disease, when disseminated lesions are already present. In such cases, the principles of debulking surgery were successfully applied especially for pelvic confined disease. However, patients presenting extended upper abdominal lesions were considered to a have a poorer outcome due to a more aggressive surgical biology. This myth was destroyed by the first studies which incorporated extended upper abdominal resections as part of debulking surgery; in Eisenhauer's study conducted between 1998 and 2003, 262 patients with advanced stage ovarian cancer

tion of the common bile duct or of the Wirsung duct [38, 39].

140 Advances in Pancreatic Cancer

isolated hepatic metastatic with mammary origin [41].

**8. Pancreatic metastases from ovarian cancer**

Pancreatic metastases from ovarian cancer usually develop as part of systemic dissemination of the malignant process, the main patterns of spread including peritoneal, hematogenous or lymphatic spread. When it comes to the pancreatic involvement due to ovarian cancer, the most commonly involved mechanisms include peritoneal and hematogenous spread.

When it comes to the association of pancreatic surgery as part of debulking surgery for advanced stage or relapsed ovarian cancer, it has been initially considered that association of such procedures will lead to the apparition of an unacceptable risk of perioperative complications. However, a study conducted by Kehoe et al. demonstrated that these surgical procedures can be successfully associated as part of debulking surgery. The authors reported a series of 17 patients submitted to distal pancreatectomies for pancreatic metastases with ovarian origin, the median age of patients being of 63 years. When it comes to the surgical outcomes, nine patients were submitted to debulking surgery to no residual disease, seven cases were submitted to optimal cytoreductive surgery while in one case a suboptimal cytoreductive surgery was performed; however, in this last case the presence of tumoral residual lesions was described at the level of the diaphragm and in the liver. When it comes to the short-term outcomes, the authors reported a morbidity rate of 24%, all patients being diagnosed with pancreatic fistulas. However, the presence of pancreatic fistulas did not impede the administration of the adjuvant therapy. Moreover, the rate of pancreatic leaks was similar to the one reported by surgeons performing pancreatic resections for pancreatic primaries, demonstrating in this way that pancreatic surgery can be safely associated as part of debulking surgery for advanced stage or recurrent ovarian cancer [44].

When it comes to the long-term outcomes after pancreatic resections for advanced stage or recurrent ovarian cancer, an interesting study was conducted in *Fundeni Clinical Hospital, Bucharest, Romania,* and was conducted by Bacalbasa et al. The study included one patient submitted to pancreatic resections as part of primary cytoreduction, four cases submitted to surgery as part of secondary cytoreduction and one case submitted to pancreatic resection as part of tertiary cytoreduction. The patient submitted to primary cytoreduction benefitted from a distal pancreatectomy in association with splenectomy which was associated to a total hysterectomy with bilateral adnexectomy, pelvic and para-aortic lymph node dissection and parcelar gastrectomy; the long-term outcome was a favorable one, the patient being diagnosed with relapse at 54 months follow-up. Patients submitted to pancreatic resections as part of secondary cytoreduction experienced a median disease free interval of 32 months and necessitated in all cases a distal pancreatectomy. Postoperatively, two patients developed pancreatic leaks which were treated conservatively in one case and through reoperation in the second case. When it comes to the long-term outcomes, the median overall survival was 36.38 months, all cases being dead of disease at the end of the study. At the time of tertiary cytoreduction, pancreatic resection was performed in a single case, 52 months after the initial diagnostic. Although the early postoperative outcome was favorable, the patient died of disease 10 months later. The authors demonstrated in this way the effectiveness of pancreatic resections as part of cytoreductive surgery in the setting of advanced stage disease as well as for patients diagnosed with recurrent lesions [45].

An interesting such case was reported by Rania Abadeer in 2010 and referred at a 43-year-old patient who was initially submitted to surgery for an adult granulosa cell tumor for which a salpingo-oophorectomy was performed. About 7 years later, the patient was diagnosed with disseminated lesions infiltrating the pelvic wall, so she was resubmitted to surgery, a total hysterectomy with left adnexectomy and bilateral pelvic lymph node dissection being performed; at that moment debulking surgery to no residual disease was achieved, the histopathological findings confirming the metastatic origin from the adult cell granulosa tumor; therefore the patient was submitted to adjuvant taxol and platinum-based chemotherapy. However, 3 years later, the patient was diagnosed with a 4.2 × 4.1 cm pancreatic cyst located at the cephalic level so a fine needle aspiration was performed, the cystic fluid presenting no signs of malignant cells. Due to the fact that the cyst continued experiencing a fast growth process, the patient was submitted to surgery, the frozen section of the cystic wall being suggestive for malignancy; due to this aspect, the surgical procedure was completed by performing a pancreatoduodenectomy. The immunohistochemical studies confirmed the metastatic origin of the lesion originating from the initial adult granulosa cell tumor. The long-term outcome was

Pancreatic Resections for Metastatic Disease http://dx.doi.org/10.5772/intechopen.75571 143

favorable, at 30 months follow-up the patient being free of any recurrent disease [46].

**9. Pancreatic metastases from uterine body or cervix cancer**

however, 6 months later, the patient remained free of recurrent disease [55].

are shown in **Table 2**.

The outcomes after pancreatic resection for pancreatic metastases with ovarian cancer origin

Pancreatic metastases from uterine primaries are other rare eventualities, only few cases being described so far [1, 54–56]. The main pattern of spread responsible for the apparition of pancreatic metastases with endometrial origin consists of hematogenous disseminations and it is usually responsible for the apparition of other distant lesions such as hepatic, pulmonary or splenic metastases [57]. Due to this aspect, pancreatic metastases from uterine carcinomas can be rarely treated with curative intent. The first authors who reported performing a surgical procedure for a pancreatic metastasis originating from an endometrial carcinoma came from the USA, in 1998; it was the case of a patient known with previous history of endometrial cancer who presented for upper digestive stenosis 3 years later. At this time, a 4 cm tumor located at the level of the uncinate process of the pancreas was found, so the patient was successfully submitted to surgery; unfortunately the authors did not report the performed surgical procedure or the outcome of this patient [2]. The first successful pancreatic resection for pancreatic metastases from endometrial cancer came from Dan Blazer, at *M.D. Cancer Center, Houston, Texas, United States of America,* in 2008. It was the case of a 56-year-old patient who had been previously submitted to surgery for endometrial cancer, at that moment a total hysterectomy with bilateral adnexectomy, pelvic and para-aortic lymph node dissection being performed; postoperatively, the patient was submitted to adjuvant radiotherapy. However, 31 months later, she was diagnosed with a pancreatic lesion measuring 3 × 3 cm in the pancreatic tail. The fine needle biopsy confirmed the metastatic origin, so the patient was resubmitted to surgery, a distal pancreatectomy being performed. The histopathological studies confirmed the metastatic origin of the lesion;


Abbreviations: DP, distal pancreatectomy.

**Table 2.** Outcomes after pancreatic resections for pancreatic metastases from ovarian carcinomas.

An interesting such case was reported by Rania Abadeer in 2010 and referred at a 43-year-old patient who was initially submitted to surgery for an adult granulosa cell tumor for which a salpingo-oophorectomy was performed. About 7 years later, the patient was diagnosed with disseminated lesions infiltrating the pelvic wall, so she was resubmitted to surgery, a total hysterectomy with left adnexectomy and bilateral pelvic lymph node dissection being performed; at that moment debulking surgery to no residual disease was achieved, the histopathological findings confirming the metastatic origin from the adult cell granulosa tumor; therefore the patient was submitted to adjuvant taxol and platinum-based chemotherapy. However, 3 years later, the patient was diagnosed with a 4.2 × 4.1 cm pancreatic cyst located at the cephalic level so a fine needle aspiration was performed, the cystic fluid presenting no signs of malignant cells. Due to the fact that the cyst continued experiencing a fast growth process, the patient was submitted to surgery, the frozen section of the cystic wall being suggestive for malignancy; due to this aspect, the surgical procedure was completed by performing a pancreatoduodenectomy. The immunohistochemical studies confirmed the metastatic origin of the lesion originating from the initial adult granulosa cell tumor. The long-term outcome was favorable, at 30 months follow-up the patient being free of any recurrent disease [46].

The outcomes after pancreatic resection for pancreatic metastases with ovarian cancer origin are shown in **Table 2**.
