**3. Results**

.

lysed cells

#### **3.1. Mental disorders in advanced cancer patients with psychogenic medical history**

Clinical studies of 17 advanced cancer patients with a psychogenic medical history showed that 100% had a variety of psychoemotional comorbidity disorders, predominantly anxiety and depression spectrum disorders. The disorders distribution was based on the International Classification of Diseases (ICD-10): generalized anxiety disorder (F41.1) – 3 (patients № 1, 13, 17), mixed anxiety and depressive disorder (F41.2) – 2 (patients № 4, 6), post-traumatic stress disorder (F43.1) – 1 (patient № 7), prolonged depressive reaction (F43.21) – 4 (patients № 3, 8, 12, 16), mixed anxiety and depressive reaction (F43.22) – 6 (patients № 2, 5, 9, 10, 11,14) and organic anxiety disorder (F06.4) – 1 (patient № 15), which in our opinion was a complication chemotherapy. The results of clinical studies of the mental state of advanced cancer patients in general have been confirmed by the data of psychometry (Table 2, the indicators 'before').

#### **3.2. Psycho-correction stage is the first stage of psychoimmunological advanced cancer treatment**

The clinical benefits after completion of HSP have been noted in all advanced cancer patients. This was confirmed by the results of psychometry and comparative analysis, which showed significant improvement in almost all of the parameters studied (Table 2). Along with a significant improvement in the mental state of cancer patients a spontaneous increase in the specific anti-tumour activity of the immune system was observed, as determined by DTH skin reaction on TAA (p<0.0008). The sustainability of mental and immunological changes was the main criterion in the decision to move to the next stage of psychoimmu‐ nological cancer treatment which is the stage of immunoactivation. In this regard, the studied parameters at the 'one month later' stage after completion of the HSP indicated the stability or instability of earlier positive changes. However, in a comparative analysis of indices in the overall group of cancer patients at stages 'after' and 'one month later' this deterioration was not evident (Table 2).

However, a careful study of the indicators at the stage 'one month later' detected a clear split of cancer patients into two groups by the intensity of DTH skin reaction on TAA (Table 3). The


**Table 2.** Psychometric indicators (SCL-90) and DTH skin reaction on TAA in advanced cancer patients before, after, and one month later after completion of HSP sessions (n=17)

DTH skin reaction was less than 5 mm in one group of patients, and was greater than 5 mm in the other group. It was found that cancer patients in these groups differed substantially in almost all psychometric parameters. The group of patients with a DTH skin reaction of less than 5 mm (11 of 17 patients) was characterized by the deterioration of psychometric indicators, which allowed us to identify this group of patients as a group with an unstable effect of correction of psychoemotional disorders (patient № 1, 3, 4, 5, 6, 7, 8, 12, 13, 15, 17).

Clinically, these patients had worsening of general and mental health, in spite of the use of antidepressants, anxiolytics, and the conduction of self-hypnosis sessions. Another group of patients whose DTH skin reaction was more than 5 mm (six patients) differed by maintenance of the previously achieved positive effects of psycho-correction with appropriate psychometric characteristics. The last group was identified by us as a group of patients with a stable effect of psycho-correction (patients number 2, 9, 10, 11, 14, 16). The close relationship of specific anti-tumour activity of the immune system with the higher nervous activity of cancer patients was confirmed by the correlation analysis between the DTH skin reaction on TAA and psychometric parameters of SCL-90 at all stages of observation (Table 4).


Mean ± s.e.m. – means and standard errors means; \*P>0.05; † - Normative values for healthy people (Tarabrina N.V., 2001)

**Table 3.** A comparative analysis of the studied parameters in cancer patients with unstable and stable effects of correction of psychoemotional disorders

DTH skin reaction was less than 5 mm in one group of patients, and was greater than 5 mm in the other group. It was found that cancer patients in these groups differed substantially in almost all psychometric parameters. The group of patients with a DTH skin reaction of less than 5 mm (11 of 17 patients) was characterized by the deterioration of psychometric indicators, which allowed us to identify this group of patients as a group with an unstable effect of

Mean ± s.e.m. – means and standard errors means; \*P>0.05; † - Normative values for healthy people (Tarabrina N.V., 2001)

**Table 2.** Psychometric indicators (SCL-90) and DTH skin reaction on TAA in advanced cancer patients before, after,

**Comparative analysis 'before-after' and 'after-one month later'**

**1 month later Mean ± s.e.m.** **P B-A** **P A-1 mon.**

**After (A) Mean ± s.e.m.**

0.75 ± 0.04 1.14 ± 0.12 0.62 ± 0.10 0.76 ± 0.11 0.002 **\***

0.66 ± 0.03 1.12 ± 0.20 0.53 ± 0.10 0.63 ± 0.11 0.006 **\***

0.51 ± 0.02 1.06 ± 0.12 0.48 ± 0.07 0.61 ± 0.10 0.0002 **\***

not defined 4.59 ±1.52 11.4 ±2.45 7.35 ±2.06 0.0008 0.003

Clinically, these patients had worsening of general and mental health, in spite of the use of antidepressants, anxiolytics, and the conduction of self-hypnosis sessions. Another group of patients whose DTH skin reaction was more than 5 mm (six patients) differed by maintenance of the previously achieved positive effects of psycho-correction with appropriate psychometric characteristics. The last group was identified by us as a group of patients with a stable effect of psycho-correction (patients number 2, 9, 10, 11, 14, 16). The close relationship of specific anti-tumour activity of the immune system with the higher nervous activity of cancer patients was confirmed by the correlation analysis between the DTH skin reaction on TAA and

correction of psychoemotional disorders (patient № 1, 3, 4, 5, 6, 7, 8, 12, 13, 15, 17).

**Indicators**

42 Updates on Cancer Treatment

Obsessivecompulsive

Interpersonal sensitivity

Global Severity

DTH skin reaction on TAA, mm

Index

**Normative values†**

and one month later after completion of HSP sessions (n=17)

**Before (B) Mean ± s.e.m.**

Somatization 0.44 ± 0.03 1.31 ± 0.16 0.67 ± 0.12 0.79 ± 0.15 0.0001 **\***

Depression 0.62 ± 0.04 1.45 ± 0.16 0.54 ± 0.09 0.84 ± 0.12 0.0002 0.004 Anxiety 0.47 ± 0.03 1.10 ± 0.15 0.35 ± 0.09 0.49 ± 0.09 0.0002 **\*** Hostility 0.60 ± 0.04 0.74 ± 0.12 0.32 ± 0.07 0.43 ± 0.08 0.007 **\*** Phobic anxiety 0.18 ± 0.02 0.55 ± 0.14 0.23 ± 0.08 0.23 ± 0.07 0.045 **\*** Paranoid ideation 0.54 ± 0.04 0.73 ± 0.16 0.43 ± 0.12 0.50 ± 0.14 **\* \*** Psychoticism 0.30 ± 0.03 0.67 ± 0.11 0.31 ± 0.07 0.41 ± 0.08 0.0006 **\***

psychometric parameters of SCL-90 at all stages of observation (Table 4).


**Table 4.** The correlation analysis between the DTH skin reaction and psychometric indicators of SCL-90 in advanced cancer patients with a psychogenic medical history on stages of observation (n=17)

The dynamics of the relationship showed that the medical and psychotherapeutic effect on the higher nervous activity of the cancer patients was accompanied by a cumulative increase in the significant negative correlations between the specific anti-tumour activity of the immune system and the mental wellbeing of cancer patients. The greatest number of correlations was observed month after the completion of HSP. Cancer patients with a sustained effect of psychocorrection (patient № 2, 10, 11, 14, 16) were proposed for a second stage of psychoimmuno‐ logical cancer treatment (stage of immunoactivation), except for patient № 9.

#### **3.3. Stage of immunoactivation: the second stage of psychoimmunological advanced cancer treatment**

The stage of immunoactivation lasted for five months and, along with the procedures of activation of specific anti-tumour immunity, advanced cancer patients took psychotropic medications and performed self-hypnosis sessions. Each procedure of epicutaneous activation of specific anti-tumour immunity was accompanied by local reactions such as redness, pain, and local itching at the injection site. All cancer patients observed pain in the area of metastatic tumour formation (including previously undiagnosed) as well as pain in the regional lymph nodes on the third day, sometimes an increased body temperature up to 37ºC, and deteriora‐ tion of health in the form of weakness, lethargy, and sleepiness. In order to relieve these reactions, patients received Nise (nimesulide) tablets 100 mg, twice per day for five to seven days. Procedures of extracorporeal activation of specific anti-tumour immunity were also accompanied by systemic reactions, but were clinically less severe than with procedures of epicutaneous activation. In addition, local reactions were observed such as redness, pain and itching at the site of local administration.

#### **3.4. Catamnesis**

The advanced cancer patients experiencing unstable clinical effects of the correction of the psychoemotional disorders (patient № 1, 3, 4, 5, 6, 7, 8, 12, 13, 15, 17) died within two to five months of the psycho-correction stage being over, except patient № 5 who died after one year. These advanced cancer patients are likely to have had more pronounced somatopsychic disorders that were not consistently removed with psycho-correction techniques and failed to influence anti-tumour immunity. Among the advanced cancer patients that were subjected to psychoimmunological cancer treatment (patient № 2, 10, 11, 14, 16) the following results were observed.

Patient № 2 is alive (five years catamnesis). The signs of haemangioma were revealed in the place of former liver metastasis (Ultrasound data) in one year following the psychoimmuno‐ logical cancer treatment.

Patient № 10 is alive, and catamnesis was two years without substantial negative dynamics. Multiple foci of fibrosis and calcification were discovered by computed tomography.

Patient № 11 is alive, and catamnesis was 6.8 years after psychoimmunological cancer treatment had finished. A very interesting fact was revealed during the research. After massive stress (she found out about her daughter's drug addiction), a quick development of the cancer disease was observed and within seven days the size of the metastasis in the only kidney increased from 38 × 23 mm to 41 × 32 mm. After the effective relief of psychoemotional disorders, metastasis regression to 12 × 11 mm was observed.

Patient № 14 is alive, and catamnesis was 1.1 years. Multiple foci of osteosclerosis without negative dynamics were observed (on computed tomography). Patient № 11 is alive, and catamnesis was 6.8 years after psychoimmunological cancer treatment had finished. A very interesting fact was revealed during the research. After massive stress (she found out about her daughter's drug addiction), a quick development of

Patient № 16 is alive, catamnesis was four years. Negative dynamics were not observed, pneumosclerosis foci and extensive fibrotic process were observed in the mediastinum (on computed tomography). the cancer disease was observed and within seven days the size of the metastasis in the only kidney increased from 38 x 23 mm to 41 x 32 mm*.* After the effective relief of psychoemotional disorders, metastasis regression to 12 x 11 mm was observed. Patient № 14 is alive, and catamnesis was 1.1 years. Multiple foci of osteosclerosis without

negative dynamics were observed (on computed tomography).

#### *3.4.1. Clinical case (patient № 9)* Patient № 16 is alive, catamnesis was four years. Negative dynamics were not observed,

Figure 3).

The dynamics of the relationship showed that the medical and psychotherapeutic effect on the higher nervous activity of the cancer patients was accompanied by a cumulative increase in the significant negative correlations between the specific anti-tumour activity of the immune system and the mental wellbeing of cancer patients. The greatest number of correlations was observed month after the completion of HSP. Cancer patients with a sustained effect of psychocorrection (patient № 2, 10, 11, 14, 16) were proposed for a second stage of psychoimmuno‐

**3.3. Stage of immunoactivation: the second stage of psychoimmunological advanced cancer**

The stage of immunoactivation lasted for five months and, along with the procedures of activation of specific anti-tumour immunity, advanced cancer patients took psychotropic medications and performed self-hypnosis sessions. Each procedure of epicutaneous activation of specific anti-tumour immunity was accompanied by local reactions such as redness, pain, and local itching at the injection site. All cancer patients observed pain in the area of metastatic tumour formation (including previously undiagnosed) as well as pain in the regional lymph nodes on the third day, sometimes an increased body temperature up to 37ºC, and deteriora‐ tion of health in the form of weakness, lethargy, and sleepiness. In order to relieve these reactions, patients received Nise (nimesulide) tablets 100 mg, twice per day for five to seven days. Procedures of extracorporeal activation of specific anti-tumour immunity were also accompanied by systemic reactions, but were clinically less severe than with procedures of epicutaneous activation. In addition, local reactions were observed such as redness, pain and

The advanced cancer patients experiencing unstable clinical effects of the correction of the psychoemotional disorders (patient № 1, 3, 4, 5, 6, 7, 8, 12, 13, 15, 17) died within two to five months of the psycho-correction stage being over, except patient № 5 who died after one year. These advanced cancer patients are likely to have had more pronounced somatopsychic disorders that were not consistently removed with psycho-correction techniques and failed to influence anti-tumour immunity. Among the advanced cancer patients that were subjected to psychoimmunological cancer treatment (patient № 2, 10, 11, 14, 16) the following results were

Patient № 2 is alive (five years catamnesis). The signs of haemangioma were revealed in the place of former liver metastasis (Ultrasound data) in one year following the psychoimmuno‐

Patient № 10 is alive, and catamnesis was two years without substantial negative dynamics.

Patient № 11 is alive, and catamnesis was 6.8 years after psychoimmunological cancer treatment had finished. A very interesting fact was revealed during the research. After massive stress (she found out about her daughter's drug addiction), a quick development of the cancer

Multiple foci of fibrosis and calcification were discovered by computed tomography.

logical cancer treatment (stage of immunoactivation), except for patient № 9.

**treatment**

44 Updates on Cancer Treatment

**3.4. Catamnesis**

observed.

logical cancer treatment.

itching at the site of local administration.

We have observed the unique clinical case of the cancer patient with malignant melanoma, who refused to receive mutilating surgery and chemotherapy but approached us for psycho‐ logical help. computed tomography). **3.4.1. Clinical case (patient № 9)** We have observed the unique clinical case of the cancer patient with malignant melanoma,

pneumosclerosis foci and extensive fibrotic process were observed in the mediastinum (on

Patient № 9, 55 years old, an accountant. In autumn 2004, melanoma localized on the neck on the left side was histologically verified. The patient turned to us on 20 January 2005. It was examined thatthe patient had a primary focus (40 x 35 mm) and multiple metastases in the neck (20 mm), supraclavicular (35 mm) and axillary (20 mm) lymph nodes on the left (see Figure 3). who refused to receive mutilating surgery and chemotherapy but approached us for psychological help. Patient № 9, 55 years old, an accountant. In autumn 2004, melanoma localized on the neck on the left side was histologically verified. The patient turned to us on 20 January 2005. It was examined that the patient had a primary focus (40 x 35 mm) and multiple metastases in the neck (20 mm), supraclavicular (35 mm) and axillary (20 mm) lymph nodes on the left (see

**Figure 3.** Localization of malignant neck melanoma, patient № 9. **Figure 3.** Localization of malignant neck melanoma, patient № 9.

Ultrasound examination of the primary tumour revealed the depth of tumour invasion in the tissues of the neck to be 25 mm.

After examination the patient was diagnosed with a psychogenic medical history (she lives with a disabled husband, who is an alcoholic), mixed anxiety and depressive reaction (F43.22) and the lack of inhibition of specific anti-tumour activity of the immune system, defined by the absence of DTH skin reaction on TAA. We observed that patients with a similar localization

and itching of the tumour foci appeared.

of melanoma die within four to six months due to profuse bleeding from the tumour foci and frequent metastasis to the brain. From 21 January to 4 February 2005 the patient underwent a course of hypnotherapy consisting of four treatment sessions and two sessions of self-hypnosis training. After treating the patient with HSP (5 February 2005), along with an improvement in general state of health and relief of anxiety and depressive disorders, positive changes were seen in a number of objective indicators. Ultrasound examination of the primary tumour revealed the depth of tumour invasion in the tissues of the neck to be 25 mm. After examination the patient was diagnosed with a psychogenic medical history (she lives with a disabled husband, who is an alcoholic), mixed anxiety and depressive reaction (F43.22) and the lack of inhibition of specific anti-tumour activity of the immune system, defined by the absence of DTH skin reaction on TAA. We observed that patients with a similar localization of

Thus, DTH skin reaction on TAA increased from 15 mm (before HSP) to 40 mm (after HSP) and maintained for two days, the absolute number of peripheral blood lymphocytes increased three times: from 709 to 1 mm3 (before HSP) to 2244 in 1 mm3 (after HSP).In addition there was a change of the vegetative (autonomic) nervous system, which was assessed by heart rate variability (HRV) [31]. HRV is the assessment of individual differences in emotional reactions, particularly in relation to social processes and mental health [32]. The total energy spectrum analysis (TP of HRV) increased 20-fold: from 213 ms2 (before HSP) to 4260 ms2 (after HSP). In addition there was a reduction in the ratio of LF/HF (normalized units) five-fold: from 2.76 (before HSP) to 0.53 (after HSP), indicating a change of state of sympathicotonia to the state of parasympathicotonia and this is a confirmation of the clinical fact of depression relief [33]. After the completion of HSP the patient conducted daily self-hypnosis sessions in accordance with our proposed programme, the content of which was aimed at forming a dense imper‐ meable capsule around the tumour foci, which like a 'plaster cocoon walls up, squeezes and strangles tumour foci'. After several self-hypnosis daily sessions lasting one hour each of the pronounced swellings of the left side of the neck and supraclavicular area with transition to the chest were observed (see Figure 4); body temperature rose up to 38ºС; and itching of the tumour foci appeared. melanoma die within four to six months due to profuse bleeding from the tumour foci and frequent metastasis to the brain. From 21 January to 4 February 2005 the patient underwent a course of hypnotherapy consisting of four treatment sessions and two sessions of selfhypnosis training. After treating the patient with HSP (5 February 2005), along with an improvement in general state of health and relief of anxiety and depressive disorders, positive changes were seen in a number of objective indicators. Thus, DTH skin reaction on TAA increased from 15 mm (before HSP) to 40 mm (after HSP) and maintained for two days, the absolute number of peripheral blood lymphocytes increased three times: from 709 to 1 mm<sup>3</sup> (before HSP) to 2244 in 1 mm3 (after HSP).In addition there was a change of the vegetative (autonomic) nervous system, which was assessed by heart rate variability (HRV) [31]. HRV is the assessment of individual differences in emotional reactions, particularly in relation to social processes and mental health [32]. The total energy spectrum analysis (TP of HRV) increased 20-fold: from 213 ms2 (before HSP) to 4260 ms<sup>2</sup> (after HSP). In addition there was a reduction in the ratio of LF/HF (normalized units) five-fold: from 2.76 (before HSP) to 0.53 (after HSP), indicating a change of state of sympathicotonia to the state parasympathicotonia and this is a confirmation of the clinical fact of depression relief [33]. After the completion of HSP the patient conducted daily self-hypnosis sessions in accordance with our proposed programme, the content of which was aimed at forming a dense impermeable capsule around the tumour foci, which like a 'plaster cocoon walls up, squeezes and strangles tumour foci'. After several self-hypnosis daily sessions lasting one hour each of the pronounced swellings of the left side of the neck and supraclavicular area with transition to the chest were observed (see Figure 4); body temperature rose up to 38ºС;

**Figure 4.** Pronounced swelling of the neck tissues after organic-oriented self-hypnosis sessions

2

The patient reported that 'stifling of the tumour' started. Within eight days the swelling completely disappeared, along with a decrease in the size of metastatic lymph nodes in the neck, supraclavicular and axillary regions. The patient continued, nearly on a daily basis, to use self-hypnosis according to an organic-oriented suggestive programme 'stifling of tumour foci'. Nine months after the beginning of organic-oriented therapeutic autosuggestion (03 November 2005), the patient underwent ultrasound examination of the tumour foci.

of melanoma die within four to six months due to profuse bleeding from the tumour foci and frequent metastasis to the brain. From 21 January to 4 February 2005 the patient underwent a course of hypnotherapy consisting of four treatment sessions and two sessions of self-hypnosis training. After treating the patient with HSP (5 February 2005), along with an improvement in general state of health and relief of anxiety and depressive disorders, positive changes were

Ultrasound examination of the primary tumour revealed the depth of tumour invasion in the

After examination the patient was diagnosed with a psychogenic medical history (she lives with a disabled husband, who is an alcoholic), mixed anxiety and depressive reaction (F43.22) and the lack of inhibition of specific anti-tumour activity of the immune system, defined by the absence of DTH skin reaction on TAA. We observed that patients with a similar localization of melanoma die within four to six months due to profuse bleeding from the tumour foci and frequent metastasis to the brain. From 21 January to 4 February 2005 the patient underwent a course of hypnotherapy consisting of four treatment sessions and two sessions of selfhypnosis training. After treating the patient with HSP (5 February 2005), along with an improvement in general state of health and relief of anxiety and depressive disorders, positive

Thus, DTH skin reaction on TAA increased from 15 mm (before HSP) to 40 mm (after HSP) and maintained for two days, the absolute number of peripheral blood lymphocytes increased

a change of the vegetative (autonomic) nervous system, which was assessed by heart rate variability (HRV) [31]. HRV is the assessment of individual differences in emotional reactions, particularly in relation to social processes and mental health [32]. The total energy spectrum

addition there was a reduction in the ratio of LF/HF (normalized units) five-fold: from 2.76 (before HSP) to 0.53 (after HSP), indicating a change of state of sympathicotonia to the state of parasympathicotonia and this is a confirmation of the clinical fact of depression relief [33]. After the completion of HSP the patient conducted daily self-hypnosis sessions in accordance with our proposed programme, the content of which was aimed at forming a dense imper‐ meable capsule around the tumour foci, which like a 'plaster cocoon walls up, squeezes and strangles tumour foci'. After several self-hypnosis daily sessions lasting one hour each of the pronounced swellings of the left side of the neck and supraclavicular area with transition to the chest were observed (see Figure 4); body temperature rose up to 38ºС; and itching of the

(before HSP) to 2244 in 1 mm3

was a change of the vegetative (autonomic) nervous system, which was assessed by heart rate variability (HRV) [31]. HRV is the assessment of individual differences in emotional reactions, particularly in relation to social processes and mental health [32]. The total energy

(after HSP). In addition there was a reduction in the ratio of LF/HF (normalized units) five-fold: from 2.76 (before HSP) to 0.53 (after HSP), indicating a change of state of sympathicotonia to the state parasympathicotonia and this is a confirmation of the clinical fact of depression relief [33]. After the completion of HSP the patient conducted daily self-hypnosis sessions in accordance with our proposed programme, the content of which was aimed at forming a dense impermeable capsule around the tumour foci, which like a 'plaster cocoon walls up, squeezes and strangles tumour foci'. After several self-hypnosis daily sessions lasting one hour each of the pronounced swellings of the left side of the neck and supraclavicular area with transition to the chest were observed (see Figure 4); body temperature rose up to 38ºС;

**15 Feb 2005** 

(after HSP).In addition there was

(after HSP).In addition there

(before HSP) to 4260 ms<sup>2</sup>

(after HSP). In

**Page No.** 

**Page No.** 

15 Fig. 5.

(before HSP) to 2244 in 1 mm3

Thus, DTH skin reaction on TAA increased from 15 mm (before HSP) to 40 mm (after HSP) and maintained for two days, the absolute number of peripheral blood lymphocytes increased

analysis (TP of HRV) increased 20-fold: from 213 ms2 (before HSP) to 4260 ms2

seen in a number of objective indicators.

changes were seen in a number of objective indicators.

spectrum analysis (TP of HRV) increased 20-fold: from 213 ms2

**Swelling**

**Figure 4.** Pronounced swelling of the neck tissues after organic-oriented self-hypnosis sessions

tissues of the neck to be 25 mm.

46 Updates on Cancer Treatment

three times: from 709 to 1 mm3

three times: from 709 to 1 mm<sup>3</sup>

tumour foci appeared.

and itching of the tumour foci appeared.

The results showed regression of metastatic lymph nodes in the neck, in the supraclavicular and axillary regions. A fibrous capsule (see Figure 5) formed deep in the tissues of the neck throughout the borders of the tumour invasion of the primary tumour focus, which actually corresponds to the content of curative autosuggestion. **Line No.**  Could you replace the figure? The correct figure is shown below.

**Line Figure 5.** Fibrous capsule around the primary tumour in the depth of the neck tissues after self-hypnosis sessions (ul‐ trasound data).

**No.**  Could you replace the figure? The correct figure is shown below. 19 Fig. 7. Further observation showed that endophytic growth of the primary tumour focus changed to exophytic growth (tumour acquired an exophytic form on the leg with a base of 23 mm) with the regression of metastatic lymph nodes in the neck, in supraclavicular and axillary regions (see Figure 6).

Hereinafter, a slow progression of the cancer process with a gradual increase of phenomena cachexia was observed. The patient died on 14 April 2008. Despite the expected death, it can be stated that the cancer patient had been able to live an active life for three years without surgeryon the neck melanoma.

**Figure 6.**Exophytic growth of melanoma with metastasis regression in the lymph nodes of the neck and supraclavicular area against self-hypnosis treatment sessions **Figure 6.** Exophytic growth of melanoma with metastasis regression in the lymph nodes of the neck and supraclavicu‐ lar area against self-hypnosis treatment sessions

#### **4. FEATURES OF OUR APPROACH 4.1. The peculiar properties of mental disorders in advanced cancer patients with a 4. Features of our approach**

#### **psychogenic medical history** The study of psychogenic medical history showed that all patients were in a state of obvious **4.1. The peculiar properties of mental disorders in advanced cancer patients with a psychogenic medical history**

caused by psychotraumatic events such as death of a close person, divorce, frequent family conflicts, change of residence, work and the presence of a disabled person in family. This long-term emotional tension was accompanied by the formation of the feeling of helplessness, hopelessness, and despair. We can assert that these future cancer patients, long before the diagnosis of cancer, already had psychogenically caused psychoemotional and psychosomatic disorders. The diagnosis of cancer itself is an additional massive and inexhaustible psychotrauma, causing emotionally paralyzing fear, or so-called 'Damocles syndrome' [34]. Cancer patients with a psychogenic medical history are those with a double massive psychotrauma. Advanced cancer patients with a psychogenic medical history undoubtedly The study of psychogenic medical history showed that all patients were in a state of obvious emotional stress before cancer diagnosis (on average for one and a half years), which was caused by psychotraumatic events such as death of a close person, divorce, frequent family conflicts, change of residence, work and the presence of a disabled person in family. This longterm emotional tension was accompanied by the formation of the feeling of helplessness, hopelessness, and despair. We can assert that these future cancer patients, long before the diagnosis of cancer, already had psychogenically caused psychoemotional and psychosomatic disorders. The diagnosis of cancer itself is an additional massive and inexhaustible psycho‐ trauma, causing emotionally paralyzing fear, or so-called 'Damocles syndrome' [34].

emotional stress before cancer diagnosis (on average for one and a half years), which was

form somatopsychic disorders along with cancer progression, so these patients were observed with a combination of psychosomatic and somatopsychic disorders that were clinically difficult to differentiate. The main feature of psychiatric disorders that we have found in cancer patients with a psychogenic medical history is that, despite the urgency of the massive psychotrauma and other conditions for the development of neuroses (known as neurotic 'Jaspers' triad'), cancer patients show a condition that is opposite to neurosis and can be defined as a state of 'deneurotization'. This phenomenon is clinically manifested by blurry, non-deployed with denial to accept, so cancer patients themselves do not consider their Cancer patients with a psychogenic medical history are those with a double massive psycho‐ trauma. Advanced cancer patients with a psychogenic medical history undoubtedly form somatopsychic disorders along with cancer progression, so these patients were observed with a combination of psychosomatic and somatopsychic disorders that were clinically difficult to differentiate. The main feature of psychiatric disorders that we have found in cancer patients with a psychogenic medical history is that, despite the urgency of the massive psychotrauma and other conditions for the development of neuroses (known as neurotic 'Jaspers' triad'), cancer patients show a condition that is opposite to neurosis and can be defined as a state of

'deneurotization'. This phenomenon is clinically manifested by blurry, non-deployed with denial to accept, so cancer patients themselves do not consider their mental condition to be sick but quite natural and situationally understandable, though very painful subjectively. This deneurotization syndrome is hard to define according to DSM-IV or ICD-10. In addition, some advanced cancer patients are observed with conditions of dissociative disorders that manifest themselves through an inconsistency of psychometric assessments to clinical studies. In other words, psychoemotional disorders in a clinical study are obvious, but psychometric parame‐ ters are within the normal limits, and vice versa. Deneurotization and dissociative disorders can insidiously hide the true extent of the level of psychopathology in advanced cancer patients and may be the cause of undiagnosed mental disorders. Thus, the study of psychiatric morbidity through a self-reported screening instrument without clinical examination does not provide a fair view of psychopathology in cancer patients.

#### **4.2. HSP as a method of choice for the quick correction of mental disorders in advanced cancer patients**

**Figure 6.**Exophytic growth of melanoma with metastasis regression in the lymph nodes of the

**Figure 6.** Exophytic growth of melanoma with metastasis regression in the lymph nodes of the neck and supraclavicu‐

**4.1. The peculiar properties of mental disorders in advanced cancer patients with a** 

The study of psychogenic medical history showed that all patients were in a state of obvious emotional stress before cancer diagnosis (on average for one and a half years), which was caused by psychotraumatic events such as death of a close person, divorce, frequent family conflicts, change of residence, work and the presence of a disabled person in family. This long-term emotional tension was accompanied by the formation of the feeling of helplessness, hopelessness, and despair. We can assert that these future cancer patients, long before the diagnosis of cancer, already had psychogenically caused psychoemotional and psychosomatic disorders. The diagnosis of cancer itself is an additional massive and inexhaustible psychotrauma, causing emotionally paralyzing fear, or so-called 'Damocles

The study of psychogenic medical history showed that all patients were in a state of obvious emotional stress before cancer diagnosis (on average for one and a half years), which was caused by psychotraumatic events such as death of a close person, divorce, frequent family conflicts, change of residence, work and the presence of a disabled person in family. This longterm emotional tension was accompanied by the formation of the feeling of helplessness, hopelessness, and despair. We can assert that these future cancer patients, long before the diagnosis of cancer, already had psychogenically caused psychoemotional and psychosomatic disorders. The diagnosis of cancer itself is an additional massive and inexhaustible psycho‐

**4.1. The peculiar properties of mental disorders in advanced cancer patients with a**

Cancer patients with a psychogenic medical history are those with a double massive psychotrauma. Advanced cancer patients with a psychogenic medical history undoubtedly form somatopsychic disorders along with cancer progression, so these patients were observed with a combination of psychosomatic and somatopsychic disorders that were clinically difficult to differentiate. The main feature of psychiatric disorders that we have found in cancer patients with a psychogenic medical history is that, despite the urgency of the massive psychotrauma and other conditions for the development of neuroses (known as neurotic 'Jaspers' triad'), cancer patients show a condition that is opposite to neurosis and can be defined as a state of 'deneurotization'. This phenomenon is clinically manifested by blurry, non-deployed with denial to accept, so cancer patients themselves do not consider their

Cancer patients with a psychogenic medical history are those with a double massive psycho‐ trauma. Advanced cancer patients with a psychogenic medical history undoubtedly form somatopsychic disorders along with cancer progression, so these patients were observed with a combination of psychosomatic and somatopsychic disorders that were clinically difficult to differentiate. The main feature of psychiatric disorders that we have found in cancer patients with a psychogenic medical history is that, despite the urgency of the massive psychotrauma and other conditions for the development of neuroses (known as neurotic 'Jaspers' triad'), cancer patients show a condition that is opposite to neurosis and can be defined as a state of

trauma, causing emotionally paralyzing fear, or so-called 'Damocles syndrome' [34].

neck and supraclavicular area against self-hypnosis treatment sessions

**11 Mar 2006** 

**4. FEATURES OF OUR APPROACH**

**4. Features of our approach**

lar area against self-hypnosis treatment sessions

**psychogenic medical history**

48 Updates on Cancer Treatment

**psychogenic medical history**

syndrome' [34].

For the fastest and most effective correction of psychoemotional disorders in advanced cancer patients, a combination approach was selected that involves the simultaneous use of psycho‐ tropic drugs and hypnotherapy. This approach was driven by the severity of the psychopa‐ thology of advanced cancer patients and the possibility of rapid progression of the cancer disease. It should be noted that hypnotherapy differs from other methods of psychotherapy by its high efficiency and velocity of clinical benefit achievement, including in oncology [35]. Thus, comparative analysis has shown that after 600 sessions of psychoanalysis 38% of patients reported feeling better, after 22 sessions of behavioural therapy 72% of patients reported a positive result, and after six sessions of hypnotherapy 93% of patients referred to the desired effect [36].

Our 26 years of clinical experience confirm the major clinical capabilities of hypnosuggestive psychotherapy in the correction of mental and psychosomatic disorders. In particular, we first discovered the phenomenon of psychogenic mobilization of CD34+CD38- stem cells [37] and an increase in telomere length in peripheral blood mononuclear cells in cancer patients during hypnotherapy [38]. Later, this phenomenon was to some extent confirmed by other researchers using psychosocial telephone counselling intervention [39]. It should be noted that because of the state of hyper-suggestiveness of advanced cancer patients there is a risk of the formation of hypnotic dependence (hypnomania), so the number of HSP sessions was limited to six sessions of hypnotherapy.

#### **4.3. DTH skin reaction on TAA as a biomarker of removing mental disorders in cancer patients**

It can be assumed that the spontaneous increase in the specific anti-tumour activity of the immune system, as determined by DTH skin reaction on TAA, reflects a relief of the psycho‐ genic immunosuppressive effects of higher nervous activity on the anti-tumour activity of the immune systems of advanced cancer patients. In fact, the DTH skin reaction appeared to be a kind of biological marker of the presence or absence of psychoemotional disorders in advanced cancer patients with a psychogenic medical history. It can be assumed that the initial absence of correlation between the DTH skin reaction and psychometric parameters was likely caused by the disintegration processes in the organism of advanced cancer patients inter alia by the violation of the interaction of the two main integrative systems of the body, which are the nervous and immune systems. The systemic impact (medication and psychotherapy) on higher nervous activity in cancer patients is accompanied by the gradual recovery of damaged linkages between the nervous and immune systems of the body. These data indicate a significant effect of higher nervous action on the anti-tumour activity of the immune system of advanced cancer patients with a psychogenic medical history.

#### **4.4. Features of immunoactivation**

The main task of the immunoactivation stage was to stimulate the specific anti-tumour immunity of advanced cancer patients by immunological methods after a spontaneous increase of their immune system's anti-tumour activity resulting from the sustained relief from psychoemotional disorders. Presumably, the effective activation of the specific anti-tumour immunity had to have a positive impact on the course of the cancer disease. We have therefore developed a method of epicutaneous (scarification) activation of specific anti-tumour immun‐ ity and an extracorporeal activation method using a small amount of peripheral blood. Both methods in preliminary studies have shown high effectiveness and safety in clinical practice (unpublished data). It should be noted in particular that the very low dose of TAA adminis‐ tered per epicutaneous led to systemic reactions in the whole body. It can be assumed that such a clinical effect was due to the specific systemic immune responses associated with the capture of TAA by antigen-presenting epidermal Langerhans cells and the migration of these cells to regional lymph nodes and antigen-presenting TAA. The latest data indicate a greater potential of CD8+ cell activation by Langerhans cells [40]. The antigen-presenting TAA in the lymph nodes leads to activation and clonal expansion of antigen-specific T cells and the subsequent development of specific inflammation in metastatic tumour foci. We observed the systemic clinical manifestations of these processes on the third day.

#### **4.5. Mind and tumour encapsulation**

Scientific and clinical evidence shows that cancer has always been primarily a local tissue process. Ideally the focus of the tumour should be immunogenic, and is supposed to be recognized by the immune system as allogeneic, and thus localized (delimitated) and de‐ stroyed by the cell-effectors of specific anti-tumour immunity. In this case, the encapsulation process is auniversalnaturalmechanismoflocalizationof anything allogeneic inthe body.This fully applies to the localization of malignant tumour formation. A fibrous capsule of a differ‐ ent density around the tumour foci has always been observed in experimental animals. It is interesting that the structure of the extracellular macromolecule matrix in capsules around the malignant and benign tumours does not differ [41]. In clinical practice, we often see a favoura‐ ble course of cancerregardless of the tissue localization when a dense fibrous capsule is formed around the tumour foci. In fact, the formation of a fibrous capsule is associated with low levels of cancer recurrence, and a capsule can serve as a mechanical and chemical barrier to metasta‐ sis [42]. Other authors in clinical practice found that the encapsulation of the tumour was an important favourable prognostic factor for survival without signs of cancer disease [43]. In this regard, we have developed an organic-oriented treatment programme for self-hypnosis, which could presumably have a decreased trophic effect on tumour tissue and contribute to the induction of tumour encapsulation. The examined clinical case confirms what is known about the significant impact of the brain and higher nervous activity on cancer[44]. Furthermore, this case presents new data on the possible nutritional (trophic) effects on tumour tissue and on suppressingthecancerprocessbydeliberateactiononhighernervousactivityincancerpatients. **03 Nov 2005 Primary tumour Fibrous capsule formation** 

Could you replace the figure? The correct figure is shown below.

**Neck skin's surface** 

**Page No.** 

**Page**

**Line** 

**Line No.** 

15 Fig. 5.

cancer patients with a psychogenic medical history. It can be assumed that the initial absence of correlation between the DTH skin reaction and psychometric parameters was likely caused by the disintegration processes in the organism of advanced cancer patients inter alia by the violation of the interaction of the two main integrative systems of the body, which are the nervous and immune systems. The systemic impact (medication and psychotherapy) on higher nervous activity in cancer patients is accompanied by the gradual recovery of damaged linkages between the nervous and immune systems of the body. These data indicate a significant effect of higher nervous action on the anti-tumour activity of the immune system

The main task of the immunoactivation stage was to stimulate the specific anti-tumour immunity of advanced cancer patients by immunological methods after a spontaneous increase of their immune system's anti-tumour activity resulting from the sustained relief from psychoemotional disorders. Presumably, the effective activation of the specific anti-tumour immunity had to have a positive impact on the course of the cancer disease. We have therefore developed a method of epicutaneous (scarification) activation of specific anti-tumour immun‐ ity and an extracorporeal activation method using a small amount of peripheral blood. Both methods in preliminary studies have shown high effectiveness and safety in clinical practice (unpublished data). It should be noted in particular that the very low dose of TAA adminis‐ tered per epicutaneous led to systemic reactions in the whole body. It can be assumed that such a clinical effect was due to the specific systemic immune responses associated with the capture of TAA by antigen-presenting epidermal Langerhans cells and the migration of these cells to regional lymph nodes and antigen-presenting TAA. The latest data indicate a greater potential of CD8+ cell activation by Langerhans cells [40]. The antigen-presenting TAA in the lymph nodes leads to activation and clonal expansion of antigen-specific T cells and the subsequent development of specific inflammation in metastatic tumour foci. We observed the

Scientific and clinical evidence shows that cancer has always been primarily a local tissue process. Ideally the focus of the tumour should be immunogenic, and is supposed to be recognized by the immune system as allogeneic, and thus localized (delimitated) and de‐ stroyed by the cell-effectors of specific anti-tumour immunity. In this case, the encapsulation process is auniversalnaturalmechanismoflocalizationof anything allogeneic inthe body.This fully applies to the localization of malignant tumour formation. A fibrous capsule of a differ‐ ent density around the tumour foci has always been observed in experimental animals. It is interesting that the structure of the extracellular macromolecule matrix in capsules around the malignant and benign tumours does not differ [41]. In clinical practice, we often see a favoura‐ ble course of cancerregardless of the tissue localization when a dense fibrous capsule is formed around the tumour foci. In fact, the formation of a fibrous capsule is associated with low levels of cancer recurrence, and a capsule can serve as a mechanical and chemical barrier to metasta‐ sis [42]. Other authors in clinical practice found that the encapsulation of the tumour was an

of advanced cancer patients with a psychogenic medical history.

systemic clinical manifestations of these processes on the third day.

**4.4. Features of immunoactivation**

50 Updates on Cancer Treatment

**4.5. Mind and tumour encapsulation**

#### **4.6. 'Cancer reparative trap': the pathophysiology of cancer in cancer patients with a psychogenic medical history**

Analysis of the literature led to the conclusion of the existence of the physiological inhibition of specific anti-tumour immunity in the reparative process (see Figure 7). **No. No.**  Could you replace the figure? The correct figure is shown below. 19 Fig. 7.

**Figure 7.** The pathophysiology of cancer in cancer patients with psychogenic medical history.

2 This local inhibition is observed in local tissue damage as a result of chemical, physical or biological exposure. For the successful healing of tissue damage, local inflammation with known cell, cytokine and vascular reactions develops in the focus. The key factor for successful tissue repair is temporary local suppression of specific anti-tumour immunity in order to avoid the elimination of proliferating cells in the damaged tissue. After completing the repair process, the local inflammation is reduced and the activity of anti-tumour immunity is restored. This natural physiological mechanism of tissue repair may become pathophysiological, i.e., as a result of chronic psychoemotional stress in the body, many foci of the stress microdamages of different tissues, which cause the formation of numerous foci of inflammation, are constantly formed. Because of the large number of inflammatory lesions in the body, there is a constant imbalance of immune reactions in the direction of maintaining reparative processes. This imbalance is accompanied by the constant systemic oppression of specific anti-tumour immunity. Under these conditions cancer tumour cells are able to grow, while the existing tumour in the body creates the possibility of the spreading of cancer. It can be stated that, in cancer patients with a psychogenic medical history, psyche is the leading factor in the development and metastasizing of cancer.

The leading role of the central nervous system in the generalization of cancer has also been shown in an animal model: in the paper of Erica Sloan and colleagues from Monash University, Melbourne, Australia, a 30-fold increase in metastasis to distant tissues from primary tumours was demonstrated in stressed mice [45]. In general, the presented cancer pathophysiological process in cancer patients with a psychogenic medical history can be called a *'cancer reparative trap'* when permanent tissue damage requires constant repair with the appropriate suppres‐ sion of anti-tumour immunity.

It should be noted in particular that permanent tissue damage is also observed to be influenced by the organism's chemical, physical and biological carcinogens. Thereby, cancer is a disease of an organism that is located in the reparative trap. Any additional damage in the body of an advanced cancer patient with a psychogenic medical history, including surgery, chemother‐ apy, or radiation therapy, enhances the phenomenon of a 'cancer reparative trap'. The elimination of mental disorders in cancer patients with psychogenic carcinogenesis leads the patient's body out of a 'cancer reparative trap' by creating the conditions for managing the cancer process and increasing the efficiency of standard cancer therapy.

#### **4.7. The role of the mind in the generalization of the cancer process**

The cellular and molecular factors and mechanisms of cancer's generalization have been presented in detail; the determinants of invasiveness and the invasion-metastasis cascade have been studied [46]; and the tumour-induced immunosuppressive network has been shown [47]. There is also evidence that biobehavioural risk factors such as social adversity, depression, and stress are involved in cancer progression [48, 49]. As mentioned above, researchers found a 30-fold increase in cancer spread throughout the bodies of stressed mice, compared with those that were not stressed. Chronic stress acts as a kind of fertilizer that feeds breast cancer progression, significantly accelerating the spread of the disease in animal models [45, 50].It can be argued with a certain degree of confidence that chronic stress is also a kind of fuel for the growth and generalization of human cancer. The results of this study suggest that the decisive role in the generalization of the cancer process for the category of advanced cancer patients with a psychogenic medical history is the psychogenic factor. This factor is shown in the form of psychogenically determined mental disorders (depressive and/or anxiety disor‐ ders), which activate and maintain the cellular and molecular mechanisms of carcinogenesis, and open the way to the generalization of the cancer process (see Figure 8).

As can be seen in Figure 8, psychoemotional disorders (depressive and/or anxiety disorders) in cancer patients during CPES are accompanied by the disintegration of the major systems in the brain [51], in particular the persistent presence of the sympathetic-adrenal-medullary and hypothalamic-pituitary-adrenal systems prevalence (fight or flight response). In the CPES state the central nervous system exerts downward tonic effect on the 'target organs', accompanied by permanent disturbances of micro-circulation to form in the tissue where the cell's damage occurred (including DNA damage) by the products of oxidative-nitrosative stress (endoge‐ nous mutagens). Permanent tissue damage in the body simultaneously accompanied sanoge‐ netic processes in order to repair damaged tissue with mandatory reciprocal inhibition of antitumour immunity for tissue healing. This is due to the fact that, with the restoration of normal tissue, proliferating cells always express a number of tumour-associated antigens; in case of the high activity of anti-tumour immunity repair processes would be difficult, since normal proliferating cells would be recognized as tumour-transformed.

different tissues, which cause the formation of numerous foci of inflammation, are constantly formed. Because of the large number of inflammatory lesions in the body, there is a constant imbalance of immune reactions in the direction of maintaining reparative processes. This imbalance is accompanied by the constant systemic oppression of specific anti-tumour immunity. Under these conditions cancer tumour cells are able to grow, while the existing tumour in the body creates the possibility of the spreading of cancer. It can be stated that, in cancer patients with a psychogenic medical history, psyche is the leading factor in the

The leading role of the central nervous system in the generalization of cancer has also been shown in an animal model: in the paper of Erica Sloan and colleagues from Monash University, Melbourne, Australia, a 30-fold increase in metastasis to distant tissues from primary tumours was demonstrated in stressed mice [45]. In general, the presented cancer pathophysiological process in cancer patients with a psychogenic medical history can be called a *'cancer reparative trap'* when permanent tissue damage requires constant repair with the appropriate suppres‐

It should be noted in particular that permanent tissue damage is also observed to be influenced by the organism's chemical, physical and biological carcinogens. Thereby, cancer is a disease of an organism that is located in the reparative trap. Any additional damage in the body of an advanced cancer patient with a psychogenic medical history, including surgery, chemother‐ apy, or radiation therapy, enhances the phenomenon of a 'cancer reparative trap'. The elimination of mental disorders in cancer patients with psychogenic carcinogenesis leads the patient's body out of a 'cancer reparative trap' by creating the conditions for managing the

The cellular and molecular factors and mechanisms of cancer's generalization have been presented in detail; the determinants of invasiveness and the invasion-metastasis cascade have been studied [46]; and the tumour-induced immunosuppressive network has been shown [47]. There is also evidence that biobehavioural risk factors such as social adversity, depression, and stress are involved in cancer progression [48, 49]. As mentioned above, researchers found a 30-fold increase in cancer spread throughout the bodies of stressed mice, compared with those that were not stressed. Chronic stress acts as a kind of fertilizer that feeds breast cancer progression, significantly accelerating the spread of the disease in animal models [45, 50].It can be argued with a certain degree of confidence that chronic stress is also a kind of fuel for the growth and generalization of human cancer. The results of this study suggest that the decisive role in the generalization of the cancer process for the category of advanced cancer patients with a psychogenic medical history is the psychogenic factor. This factor is shown in the form of psychogenically determined mental disorders (depressive and/or anxiety disor‐ ders), which activate and maintain the cellular and molecular mechanisms of carcinogenesis,

As can be seen in Figure 8, psychoemotional disorders (depressive and/or anxiety disorders) in cancer patients during CPES are accompanied by the disintegration of the major systems in the brain [51], in particular the persistent presence of the sympathetic-adrenal-medullary and

cancer process and increasing the efficiency of standard cancer therapy.

and open the way to the generalization of the cancer process (see Figure 8).

**4.7. The role of the mind in the generalization of the cancer process**

development and metastasizing of cancer.

sion of anti-tumour immunity.

52 Updates on Cancer Treatment

The reparative focus of the immune systems of cancer patients with a psychogenic medical history is shown in a shift of balance T-helper-1/T-helper-2 lymphocyte subpopulations in the predominance of T-helper-2 lymphocyte subpopulations and a significant increase in the tissues of alternatively activated macrophages (M2 macrophages). These M2 macrophages secrete IL-10, CCL17, CCL22, CCL18, IL-1RA, and IL-1R decoy. M2 macrophages are active workers of the host, promoting the scavenging of debris, angiogenesis, remodelling, and repair of wounded/damaged tissues [52].

It is known that alternatively activated macrophages in tumour foci orient the immune response towards the activation of repair processes in cancer centres, supporting them in inflammation and angiogenesis, i.e., determining tumour growth and metastasis [53]. In tumour foci M2 macrophages take up to 50% of the tumour mass [54]. It should be particularly noted that the induction of M2 macrophages is influenced by stress hormones – corticosteroids [52]. Thus, there is every reason to believe that the growth of the tumour and the generalization of cancer in the body of patients with a psychogenic medical history are determined by the phenomenon of the reparative focus (direction) of their immune system.

Our clinical observations suggest that cancer patients in general (and with a psychogenic medical history in particular) suffer colds, bacterial and fungal diseases no more and for no longer than healthy people. This points to the selective suppression of anti-tumour immunity but not completely compromising the immune system of cancer patients. Moreover, almost all cancer patients note a common or even accelerated healing of wounds, cuts, and scratches. These clinical data also reflect the reparative orientation of the immune system of cancer patients. In our view, the need to prove empirically the categorical prohibition of any cancer patient physiotherapy, enhancing tissue repair processes in the body, is connected with this phenomenon. The abovementioned fully applies to some psychotherapy. In particular, for cancer patients with psychoemotional disorders that have not been eliminated, the use of various relaxation techniques as well as self-hypnosis a hypnotic inductions of warmth, improvement of blood supply and other trophically-oriented hypnotic inductions, result in the rapid progression of the cancer process. Moreover, cancer patients with psychoemotional disorders that have not been eliminated who relax at the spa, make tourist trips and so on to relieve stress, relax, escape, and recover, often experience progression of the cancer process shortly after returning home.

Thus, the generalization of cancer in cancer patients with a psychogenic medical history depends on the availability of psychoemotional disorders that have not been eliminated repair of wounded/damaged tissues [52].

workers of the host, promoting the scavenging of debris, angiogenesis, remodelling, and

**Figure 8.**The role of chronic stress (mental disorders) in the generalization of the cancer process in patients with psychogenic medical history. (a) Psychoemotional disorders (anxiety, depression) as a result of chronic stress in cancer patients with psychogenic medical history are accompanied by permanent damage to body tissues and compensatory systemic activation of sanogenetic processes to repair damaged tissue. These system recovery processes are inevitably accompanied by systemic suppression of anti-tumour immunity, paving the way for the generalization of the cancer process; (b) Sustainable relief of psychoemotional disorders in cancer patients restores the natural system activity of anti-**Figure 8.** The role of chronic stress (mental disorders) in the generalization of the cancer process in patients with psy‐ chogenic medical history. (a) Psychoemotional disorders (anxiety, depression) as a result of chronic stress in cancer patients with psychogenic medical history are accompanied by permanent damage to body tissues and compensatory systemic activation of sanogenetic processes to repair damaged tissue. These system recovery processes are inevitably accompanied by systemic suppression of anti-tumour immunity, paving the way for the generalization of the cancer process; (b) Sustainable relief of psychoemotional disorders in cancer patients restores the natural system activity of anti-tumour immunity and promotes the localization of the cancer process.

tumour immunity and promotes the localization of the cancer process.

associated with compromising their anti-tumour immunity. In this regard, early detection and relief of psychoemotional disorders in cancer patients with a psychogenic medical history could prevent the transition of these patients to the category of advanced cancer patients. At the same time, advanced cancer patients with a psychogenic medical history may have a more favourable prognosis after they receive pathogenetically substantiated psychoimmunological treatment. It is known that alternatively activated macrophages in tumour foci orient the immune response towards the activation of repair processes in cancer centres, supporting them in inflammation and angiogenesis, i.e., determining tumour growth and metastasis [53]. In tumour foci M2 macrophages take up to 50% of the tumour mass [54]. It should be particularly noted that the induction of M2 macrophages is influenced by stress hormones – corticosteroids [52]. Thus, there is every reason to believe that the growth of the tumour and

#### **5. Further research**

Clinical practice shows that there are always those with frequent inexplicable recurrences of cancer, resistance to cancer therapy, rapid generalization of the cancer process and common side effects of cancer treatment. Many of these cancer patients are likely to be those with a psychogenic medical history. In order to conduct the successful treatment of such difficult cancer patients, the efficient impact on higher nervous activity of extensive drug and non-drug resources is required. The psychogenic factor is a major pathogenic

3

factor in cancer patients with a psychogenic medical history (psychogenic carcinogenesis), which operates continuously at all stages of cancer, unlike chemical, physical and biologi‐ cal carcinogenesis. This is particularly important for clinical practice, since it makes it possible to develop a new approach to pathogenesis-based therapeutic-diagnostic and rehabilitation cancer therapies (see Figure 9).

*At the diagnostic stage*, the group of cancer patients for which the psychogenic factor is patho‐ genetically significant can be distinguished. For this patient group we earlier proposed the clinical criteria of psychogenic carcinogenesis and developed a diagnostic test for the evalua‐ tion of the specific anti-tumour activity of the immune system [25]. At this stage, as in the subsequent stages of cancer, the integrative-oncology approach is required, involving psychi‐ atric or clinical psychological assistance.

*At the therapeutic stage*, the purposeful detection of mental disorders in cancer patients and their efficient elimination in combination with the standard therapy of cancer is required. It is necessary to develop new drugs in order to conduct standard cancer therapy with a simulta‐ neous impact on higher nervous activity in cancer patients. The development of new drugs and approaches to block the reparative orientation of the immune system in cancer patients is also required. Perhaps this will be the application of low doses of cytotoxic drugs in combi‐ nation with nonsteroidal anti-inflammatory drugs and other drug combinations. **Page No. Line No.**  Could you replace the figure? The correct figure is shown below. 23 Fig. 9.

associated with compromising their anti-tumour immunity. In this regard, early detection and relief of psychoemotional disorders in cancer patients with a psychogenic medical history could prevent the transition of these patients to the category of advanced cancer patients. At the same time, advanced cancer patients with a psychogenic medical history may have a more favourable prognosis after they receive pathogenetically substantiated psychoimmunological

It is known that alternatively activated macrophages in tumour foci orient the immune response towards the activation of repair processes in cancer centres, supporting them in inflammation and angiogenesis, i.e., determining tumour growth and metastasis [53]. In tumour foci M2 macrophages take up to 50% of the tumour mass [54]. It should be particularly noted that the induction of M2 macrophages is influenced by stress hormones – corticosteroids [52]. Thus, there is every reason to believe that the growth of the tumour and

**Figure 8.**The role of chronic stress (mental disorders) in the generalization of the cancer process in patients with psychogenic medical history. (a) Psychoemotional disorders (anxiety, depression) as a result of chronic stress in cancer patients with psychogenic medical history are accompanied by permanent damage to body tissues and compensatory systemic activation of sanogenetic processes to repair damaged tissue. These system recovery processes are inevitably accompanied by systemic suppression of anti-tumour immunity, paving the way for the generalization of the cancer process; (b) Sustainable relief of psychoemotional disorders in cancer patients restores the natural system activity of anti-

**Figure 8.** The role of chronic stress (mental disorders) in the generalization of the cancer process in patients with psy‐ chogenic medical history. (a) Psychoemotional disorders (anxiety, depression) as a result of chronic stress in cancer patients with psychogenic medical history are accompanied by permanent damage to body tissues and compensatory systemic activation of sanogenetic processes to repair damaged tissue. These system recovery processes are inevitably accompanied by systemic suppression of anti-tumour immunity, paving the way for the generalization of the cancer process; (b) Sustainable relief of psychoemotional disorders in cancer patients restores the natural system activity of

tissues of alternatively activated macrophages (M2 macrophages). These M2 macrophages secrete IL-10, CCL17, CCL22, CCL18, IL-1RA, and IL-1R decoy. M2 macrophages are active workers of the host, promoting the scavenging of debris, angiogenesis, remodelling, and

CANCER PATIENTS

**(mental disorders) a b** 

**Integration brain systems and balance of organism functional systems** 

**Mental Health (recovered)** 

**System balance of tissue healing (reparative process) and anti-tumour immune processes (Th1/Th2 and M1**/**M2 macrophage balance)** 

**Localization of cancer process** 

repair of wounded/damaged tissues [52].

54 Updates on Cancer Treatment

**Disintegration brain systems (HPA and SAM systems)** 

**Chronic Stress** 

**Permanent tissue damage (ischaemic, metabolic disorders, oxidativenitrosative stress)** 

**Compensatory system tissue healing and reciprocal system inhibition of anti-tumour immunity (Th1<Th2 and M1<M2 macrophage imbalance)** 

> **Generalization of cancer process**

tumour immunity and promotes the localization of the cancer process.

anti-tumour immunity and promotes the localization of the cancer process.

Clinical practice shows that there are always those with frequent inexplicable recurrences of cancer, resistance to cancer therapy, rapid generalization of the cancer process and common side effects of cancer treatment. Many of these cancer patients are likely to be those with a psychogenic medical history. In order to conduct the successful treatment of such difficult cancer patients, the efficient impact on higher nervous activity of extensive drug and non-drug resources is required. The psychogenic factor is a major pathogenic

treatment.

**5. Further research**

	-
	-
	-

**Figure 9.** Future promising clinical approaches to advanced cancer treatment.

*At the additional cancer treatment stage and stage of cancer rehabilitation* it is necessary to preserve mental health and the specific anti-tumour activity of the immune system. In this regard, we have developed and tested an anti-relapse psychoimmunological approach to the treatment of advanced cancer patients with a psychogenic medical history using a special method of hypnotherapy and original techniques of epicutaneous and extracorporeal activation of specific anti-tumour immunity.

Thus, the early diagnosis of cancer patients with psychogenic medical history and the use of pathogenesis-based cancer treatment will allow reducing financial costs and improving the results of cancer treatment.

### **6. Conclusion**

The present study revealed there to be a special group of advanced cancer patients by the presence of their psychogenic medical history, comorbid psychoemotional disorders, and suppressed specific anti-tumour activity of the immune system. The above mentioned characteristics, we believe, are the clinical criteria of psychogenic (stressful) carcinogenesis [25]. Therefore, the comorbid psychoemotional disorders of this group of advanced cancer patients have a major influence on the course and outcome of the cancer disease. These patients need to receive a special psychoimmunological treatment, consisting of two strictly sequential steps: elimination of psychoemotional disorders, and activation of specific anti-tumour immunity. At the same time, the impossibility of the sustained relief of psychoemotional disorders in advanced cancer patients at the first stage of cancer treatment excludes a further transition to the immunoactivation stage, and can be considered to be an adverse prognostic factor with regard to the lives of these patients. The results of this study are preliminary and require further clinical evidence on a larger contingent of patients with cancer, and may be interesting to various professionals involved in treating advanced cancer patients.

#### **Acknowledgements**

The authors gratefully acknowledge Alexey Palchevsky (Kaliningrad, Russian Federation) for financial support and Andrei Kovalevskii MD (Kazakhstan), RMT (Canada) for the Russian/ English translation and proofreading of this article.
