In March 2009 Mr Paresh Kant, the representative of the Indian business circles, visited the “Pulse” company.
The leading experts of the company informed the Indian guest about engineering and technological “know-how”, applied for producing the cryosurgical equipment, about its technical characteristics, fields of medical application as well as clinic techniques.
The guest was satisfied with the high quality of manufacturing of the main product of the company – the cryosurgical equipment “Cryo-Pulse”, its reliability, simplicity and technological fine-tuning, which allow applying it in different fields of medicine and in different clinics ranged from the most advanced to the rural hospitals without involvement of specially-trained technical staff.
The guest was informed about the main advantages of the unit “Cryo-Pulse” as compared to other existing analogues, in particular the high freezing power (reaching the temperature of cryoexposure of minus 180 degrees of Celcius and lower in contact with the subject under freezing), the capability of sustaining the temperature of cryoexposure at any temperature level within working range, universality, efficiency, reliability, safety and ease in application.
He was presented a number of statistical and scientific data as well as positive feedbacks from the leading medical institutions of Ukraine, Russia, Austria, which confirm the excellent results of thousands of operations, exercised by the doctors of various clinics and in various fields of medicine with assistance of cryosurgical unit “Cryo-Pulse”.
Mr Paresh Kant as the biologist by education highly assessed the advantages of the application of slightly traumatic cryosurgical method in treatment of a number of severe diseases, including the oncological ones. During many years the units “Cryo-Pulse” have widely applied in treatment of liver tumors, pancreas tumors, skin cancer, prostate tumors, breast cancer and gynecologic diseases.
Mr Paresh Kant expressed his confidence that high technical and operating characteristics of the cryosurgical unit “Cryo-Pulse” and clinical results of its practical application would raise huge interest of Indian doctors in cryosurgical method and the unit “Cryo-Pulse”. Mr Paresh Kant expressed his readiness to promote the distribution of Ukrainian cryosurgical equipment to the medical institutions of the Republic of India.
Among the future plans of the company “Pulse” there is the organization of a workshop on application of the cryosurgical unit “Cryo-Pulse” on the basis of one of the leading Indian medical centers. Moreover, the demonstrative operations will be made by the prominent Ukrainian doctors, who are the representatives of modern Ukrainian medical science.
The Parties expressed their confidence that the application of the newest Ukrainian cryotechnologies of the XXI century would promote improvement of health care for thousands of citizens of India.

On November 14, 2007, universal cryosurgical apparatus “Cryo-Pulse” was delivered to Chernigov regional oncological center. Doctors in Chernigov were already familiar with cryosurgical method of treatment and knew that efficiency of this method directly depends on technical parameters of cryosurgical apparatus. When engineers of “Pulse” CPF explained principles of control of “Cryo-Pulse” unit, Vladimir Nikolaevich Zotov, the Head physician of the center, noted that apparatus is easy-to-handle and has high refrigerating capacity.

The beginning of the XXI-st century is the period of impetuous application of cryosurgical method of treatment in clinical practice all over the world, and the 14th International congress of cryosurgery held on 3-6 November, 2007 in Beijing (China) was the evidence of it.

More than 150 delegates from 30 countries all over the world were congress participants. Ukraine was represented by the group of medical scientists and physicists led by Yaroslav Zharkov, director of “Pulse” scientific-and-production firm (CPF). All reports made by Ukrainian scientists have attracted keen interest of leading cryosurgeons of the world. Ukrainian doctors presented results of cryosurgical method in treatment of breast tumours (Prof. A.A. Lytvynenko, Deputy Director of the Institute of Oncology AMS of Ukraine), neoplasms in female reproductive organs (Prof. A.Ya. Senchuk, Head of the chair of obstetrics and gynecology at the Medical institute of the Ukrainian association of folk medicine), tumours of head, neck and skin (O.O. Galay, cand. med. sci., Head of the head and neck department at Lviv State oncologic regional medical-diagnostic centre). Yaroslav Zharkov, Director of “Pulse” CPF, has presented construction of universal cryosurgical unit “Cryo-Pulse” which, according to the experts’ evaluation, is definitely superior to the best domestic and foreign analogues in technical parameters.

Congress participants have noticed growing popularity of cryosurgical method of treatment, first of all, in oncology. The cryosurgery by right becomes an independent effective field of medicine, and Ukrainian cryosurgeons occupy leading position there.

Modern surgery is impossible to be imagined without low-invasive interventions minimizing trauma of patients. Today, using, particularly, cryogenic temperatures, relative simplicity of manipulations succeeded to be reached almost painless performance, no bleedings, high accuracy and efficiency of treatment in different branches of medicine, especially when traditional methods of therapy appear to be helpless.

Though cryosurgery cannot be considered as panacea in all possible operative measures, nowadays this set of cryosurgical technologies which experts usually use in complex therapy of patients is a perspective method of treatment. Today Ukraine is of interest for foreigners because of active introduction of cryosurgical method in different branches of medicine, as the newest cryosurgical device “Cryo-Pulse” was invented exactly in our country, and the method itself is not worthy without it.

Some days ago, delegation of Indian specialists visited Kyiv and had conversation with leading experts used cryosurgery in practical medicine.

Practice is the measure of knowledge and method assessment

First of all the Indian experts, practitioner Chandagal Madhu, doctor Ball Baskaran and businessman Hemant Kumar, have become interested in the most widespread diseases which are common for all mankind irrespective of residing area: tumours of skin, head and neck, breast cancer, tumours of liver and pancreas, as well as using of cryosurgery in gynecology and proctology where the newest technologies not only facilitate reaching of desired effect but also prolong life of patients and keep quality of their life.

Visitors were convinced that it all became possible thanks to unique domestic device “Cryo-Pulse” which allows to reach optimum temperature in the focus of lesion, acting precisely on targeted pathological area, and not damaging healthy tissues. Earlier nobody can achieve it.

The result of using of cryogenic temperatures (to 190 degrees subzero centigrade) depends on technical parameters of cooling process: slow freezing and slow thawing is favourable for tissues conservation (cryotherapy), and the snap-freezing and slow thawing resulted in its destructions (cryodestruction).

Visitors from India were interested exactly in destruction of pathological cells and tissues. Therefore itinerary of their visit to capital considered their wishes first of all. Ukrainian specialists who use method of cryodestruction over 7-10 years were selected. They were Igor Palazyuk, highest category cancer surgeon from the Department of tumours of skin, head and neck at the Regional hospital No. 1; Professor Oleksandr Lytvynenko, Doctor of medical sciences, Head of the Department of general oncology and reconstructive surgery of breast at the Institute of oncology АМSU; Professor Volodymyr Chernev, Chief of the Department of abdominal and low-invasive surgery, Colonel of medical service of the Main military clinical hospital of the Ministry of Defense of Ukraine; Professor Oleksiy Dronov, Doctor of medical sciences, Head of the Chair of general surgery No. 1 at the Bogomolets NMU, Scientific supervisor of the Kyiv centre of liver, gall ducts and pancreas; Professor Anatoly Senchuk, Doctor of medical sciences, Head of the Chair of obstetrics and gynecology of the Medical institute of the Ukrainian association of folk medicine; Vladyslav Korolenko, candidate of medical sciences, Assistant of the Chair of faculty surgery at the Bogomolets NMU, Chief coloproctologist of the Southwest railway of the Road hospital No. 1, Kyiv.

Death of pathological cells during cryodestruction

Process of cryodestruction includes number of responses, where the following mechanisms involved:

* — thermal shock which is evident when protoplasm became immobile;
* — appreciable dehydration of cells during formation, first, extracellular, and then intracellular ice;
* — formation of intracellular crystals of ice, mechanical destruction of cellular membrane and compression of cells with crystals;
* — denaturation of cellular proteins and phospholipids in cellular membranes;
* — microvascular trauma or termination of circulation in the refrigerated tissue resulted into necrosis.

Histological evidences show that connective tissue and elastic structure of an organ are preserved after cryodestruction. The positive is that after thawing blood flow is recommenced in great vessels (inferior vena cava, portal vein, aorta and major artery) and damaged endothelium promptly regenerates. This cryotechnological peculiarity allows to perform cryodestruction of nonresectable tumours extended in great vessels. Temperature intervals of cell death are specific for every tissue. In particular, blood vessels and bone tissue are proved to have the greatest resistance to freezing, so cell destruction is reached at the lower temperatures.

Therefore Indian experts were interested almost in everything: temperature regimens and time for freezing tumours of different localization, areas for tissues freezing and thawing, cryoinstrumentation and cryoapplicators, long-term results of cryodestructiones etc.

Application of cryogenic temperatures, in particular, during the surgery of breast cancer which visitors observed in Oleksandr Lytvynenko’s masterly performance at the Institute of Oncology AMS of Ukraine, and they were impressed with both effect of operation and skill of surgeon. Professor often has to deal with nonresectable tumours which, by means of chemiotherapy, he firstly “transforms” into resectable form and then, after tumour cryodestruction, performs mastectomy. During freezing tumour not only perishes, but it also lost ability to dissemination. Long-term results shows that rate of recurrence-free survival of patients who undergone tumour cryodestruction before mastectomy is 27 %.

Cryodestruction allows to minimize surgical traumatism, in particular, in metastatic neoplasms of liver. For the first time in world surgical practice, manufacturers of cryosurgical equipment together with medical practitioners have developed method of laparoscopic cryodestruction of hepatic and pancreatic tumours. For this purpose special cryolaparoscopic instrument was designed, and one of inventors and at the same time doctor-practitioner Volodymyr Chernev shows it to guests.

- The idea of creating this unique instrument appeared when optimum accesses to different departments of liver and for different levels of tumours localization had emerged, - Colonel of medical service tells. - This search became more urgent with a rush of patients which have already undergone some operative measures and more than one course of chemiotherapy. They were physically and morally emaciated people whom traditional methods were contraindicated because of high trauma and non-optimistic consequences. At the same time laparoscopic cryodestruction allows not only to minimize trauma, but also promote prompt patients rehabilitation. Survival rate for such patients increased on the average from several months to several years. In respect of survival we were helped by specialists from metropolitan Kavetsky Institute of Observational pathology, oncology and clinical radiobiology NAS of Ukraine who made from excised tumour autovaccine for patients able to raise immune status of the body. Experts from India were interested in diameter of tumour exposed to freezing because it can be larger than cryoapplicator used for cryodestruction. Volodymyr Chernev’s practice shows that diameter covered the following field of freezing must partly overlap the previous one even so that full coverage of tumour provides for 1 cm increasing of diameter covering of healthy tissue. To eliminate tumour extended into the great vessel is impossible without cryomethod. Indian guests were convinced in it when observed three parallel operations (two on pancreas of different localization and on liver) performed by Professor Oleksiy Dronov.

- Now I wonder how we can did without cryosurgery earlier, - professor tells. - Cryosurgical method gives an opportunity not only to eliminate tumours almost inaccessible to traditional procedures, but also influence the further effective treatment of patients, in particular, chemotherapy. Certainly, it became possible only thanks to application of the present rector of the Medical University, Professor Vitaly Moskalenko, Doctor of medical sciences, when four cryosurgical devices “Cryo-Pulse” were purchased for leading chairs of Bogomolets NMU some years ago. Now young generation studies on them according to the rector’s order.

Also, good effects of cryomethod guests saw in maternal clinic KMCH No.1 where Professor Anatoly Senchuk works. Efficacy rate of the newest method used in treatment of patients with precancer diseases of uterine cervix is 98,5 %. Cryosurgery in gynecology is highly effective, low-invasive and performed in out-patient facilities, and is applied in treatment of other diseases which earlier caused women disability (adenomiosis, endometrial cancer, etc.). Now, thanks to the newest technologies, we can help great number of women whom surgical treatment and hormonal therapy are contraindicated because of number of concomitant pathologies, such as diabetes mellitus, obesity, varicose disease, etc.

Advantages and potential of cryosurgical method

* — Allows to destroy completely the given volume of pathological tissue both on surface and in the deep of a body.
* — Low trauma.
* — Painless.
* — Practically bloodless.
* — Ablastic, dissemination of malignant cells is excluded.
* — Good in complex treatment.
* — Multiple cycles of exposure are possible.
* — Expands potential of radical treatment.
* — Does not cause coarse cicatrices.
* — Possible immune responses of a body against preserved recurrent malignant cells.

Vira FAZLEYEVA

During the last week, Vietnamese specialists in military medicine and technology were acquainted with the clinical aspects of cryosurgery in the leading Kyiv Institutes and Hospitals. Their visit to the capital was continuation of the fruitful cooperation initiated by representatives of both parties at the end of the last year. Then the Ukrainian producers of cryosurgical equipment of “Pulse” SPC visited Vietnam on an intergovernmental delegation on the Days of Ukrainian Science and Technology in Vietnam, where the achievements of the Ukrainian science and advanced technologies were displayed.

Then the Managing Director of the Advanced Technologies Center of the Vietnamese Academy of Sciences, Doctor Le Hu Ziyen and Head of General Surgery Department of Central Military Hospital in Hanoi, Colonel of medical service Chieu Cheu Ziong expressed their wish to be acquainted with the clinical aspects of cryosurgery in various spheres of surgery in the country-producer of “Cryo-Pulse” cryosurgical plant.

The Vietnamese guests “made” their Kyiv colleagues answer their numerous questions, display the advantages of the modern method, and explain in detail, an in general, pass certification of “maturity” of the local technology.

The program of visit of the Vietnamese colleagues was heavy and diversified. The foreign specialists visited the Central Military Clinical Hospital of the Ministry of Defence of Ukraine, Hospital of the Internal Ministry of Ukraine, the Kyiv Regional Clinical Hospital, the Kyiv City Oncological Hospital, Institute of Oncology of AMS of Ukraine, Medical Institute of Ukrainian Association of Folk Medicine, as well as several basic Chairs of O.O. Bogomolets National Medical University and of P.L. Shupik National Medical Academy of Postgraduate Education.

The Vietnamese specialist took a keen interest in clinical application of cryosurgery and cryotherapy in the cases of oncological diseases of hepatopancreatobiliar zone, in urology, obstetrics and gynecology, malignant tumors of head and neck, proctology, dermatology, and in case of mammary gland cancer. The radical and palliative methods of intervention, applied at present in cryosurgery, differ in operation technique. The following techniques may be applied: cryoablation (complete radical cryodestruction of a tumor or organ), cryoresection (cryodestruction with further resection of the frozen part of organ), cryoextirpation (fixation of the pathological area to cryoapplicator by way of freezing), and adjuvant cryodestruction (as an additional method after the basic stage of operation with the use of the traditional method). The foreigners highly appreciated the advantages of the cryosurgical method over a traditional operation, as in case of a cryosurgical operation, alongside with usual radical cryosurgical destruction; the inoperable tumors are subject to destruction as well. The Vietnamese specialists visited twice the operation room of the Head of General Surgery Chair No. 1 of O.O. Bogomolets NMU, Research Supervisor of the Kyiv Center for Surgery of Liver, Biliary Ducts, and Pancreas, Doctor of Medicine Oleksiy Dronov, where they witnessed resection of a thirty-kilogram tumor from abdomen. To save life of the patient became possible greatly owing to excision of a malignant tumor with further application of cryotechnology.

The foreigners made sure of great prospects of cryotechnology after their meeting with the oncology surgeon of the Oncology Chair of P.L. Shupik National Medical Academy of Postgraduate Education (NMAPE), Doctor of Medicine professor Rakhman Taschiyev who operates malignant tumors of abdominal zone and mammary gland cancer that is widely spread now, with the application of cryodestruction method. He thoroughly studies the processes occurring in the pathological organ and of a patient following cryosurgical intervention and records them, as the new method consists of two stages — freezing and natural thawing of tissue without heating, and understanding the capabilities of such processes may influence the final results of cryosurgical interventions. In particular, the professor noticed that at the stage of thawing, antitumor antigens are formed in the pathological organ and with blood circulation are spread over the whole body. Thus, owing to cryo-influence, a body is able to elaborate its own vaccine against malignant neoplasms that prolongs the life of certain patients with oncopathology of hepatopancreatobiliar zone for 10-12 years. In availability of multiple metastatic affection, when cryoapplicator renders harmless the largest tumor of the pathological nidus with diameter of up to 3 mm, all small oncological tumors would resolve owing to cryodestruction, which has a strong immunogenic influence. Taking account of the fact that a steady growth of the incidence rate of mammary gland tumor (MGT) is observed during the last years, holding the first place among oncological diseases and the third place as to mortality rate, the application of cryosurgical methods of treatment in combination with complex MGT treatment (radical mastectomy, radiotherapy, chemotherapy, and hormonotherapy) gives positive results. The last two years’ observation of patients that were subject to cryosurgical treatment with self-vaccination, evidences the absence of recrudescences and metastases, prolongation of life of the women and improvement of its quality, whereas the application of the traditional methods alone for MGC treatment proves occurrence of cancer recrudescence in 15-20% of the operated women. Therefore, owing to cryosurgery, the operative interventions became organ-sparing, practically bloodless, have promising late results and are low-traumatic.

Not without reason they say that it is better to see once than to hear several times. The Vietnamese specialists were fully satisfied with everything seen and heard by them. It is not only impression that they will bring to their country, but also a contract for purchase of the modern cryogenic equipment for the medical establishments of Vietnam, the experience of application of cryosurgical methods of treatment in various spheres of medicine, which at present are illimitable.

Yu.V. Patiutko, D.V. Podluzhnyi, A.G. Kotelnikov, I.V. Sagaidak

Moscow,The N.N. Blokhin Institute of Clinical Oncology of Russian Oncological Center of RAMS
Liver and Pancreas Surgery Ward

The cryogenic method belongs to the challenging methods in therapy; it is increasingly used in medical practice in general, and in oncology in particular. In the recent years, the cryogenic method has been applied in oncourology, oncogynecology, and hepatology. At present, the cryosurgery is gradually moving forward to occupy its deserved position in treatment of pancreas tumors as well. However, there are scarcely any publications in the foreign and local literature on the subject of treatment of pancreas malignant tumors. Thus, in the available literature S.A. Shalimov, L.V. Keisevich, and A.A. Litvinenko (Ukraine, 1998) describe the method and results of treatment of 89 pancreas malignant tumor cases. The survival rate was as follows: 1 year - 29%, 3 years - 10%. At that, the authors collected all histological variants of tumors and did not conduct a remote survival analysis separately by each nosological form. Besides, the article describes the process of cryodestruction of the head of a pancreas as an independent treatment method without further pancreatoduodenectomy. In doing so, the authors do not exemplify the structure and number of postoperative complications, although, based on our experimental data, the risk of damage of duodenum wall with further development of necrosis and perforation is high enough. In general, the hollow organs located close to the point of cryoapplication must be handled with extreme care. Once we had to perform a distal resection of stomach for the avoidance of its damage in the process of cryodestruction of a pancreas body tumor in head transition.

G. Prokhorov with co-authors (Saint-Petersburg, 2005) exemplify the experience of cryosurgical treatment of 4 patients locally-spread pancreas tumors in the course of combined therapy. The maximum survival of these patients was 26 months. The median was 12.1 months.

The study of cryodestruction mechanisms, selection of the optimum exposure conditions for achievement of maximum destructive effect in tissues is the subject and the task of cryosurgery. The extent and volume of damage depend not only on the preset temperature and time parameters, but also on the type of the tissue exposed, on its resistance to low temperatures and adaptability (Lozina-Lozinskaya, 1972). In fact, the process of freezing of live biological structures, with water as their main component, consists in its transition from one aggregation state to other, but is far from being similar to purely physical process of crystallization. It is many orders more complicated and represents a complex of physical-chemical and biochemical changes (J. Coe, S. Rockoff, A. Omaya, 1965, J. Cooper, 1965, P. Mazur, 1970). The investigations conducted by many authors allow conclusions that quick freezing is more detrimental for cells that slow freezing. Besides, it is notorious, that quickly frozen cells containing intracellular ice, are more likely damaged at the stage of slow thawing than at the stage of freezing. The matter of cell survival following low-temperature application is of significance, especially in oncology. The low-temperature resistance of cells and their survival depend on the structural and functional features of organs and tissues, and are defined by the critical temperature. The range of critical temperatures for survival of various cell elements and tissues is from minus 5°C to minus 50°C (P. Mazur, 1970).

Clinical data

At the N.N. Blokhin Institute of Clinical Oncology of Russian Oncology Center of RAMS, cryosurgical treatment of pancreas tumors was conducted in 54 patients. At that, the following cryoapplication variants were used:

1. Cryogenic treatment of tumors as an independent method. It was used for non-resectable pancreas tumors.
2. Cryoapplication in combination with radical operation.
3. Cryosurgery in combination with radiation therapy. The cryodestruction was supplemented by remote radiotherapy with fractionated dosage, or by remote gamma-therapy.
4. Cryosurgery in combination with chemotherapy. The cryodestruction was supplemented by the standard schemes of polychemotherapy.
5. Cryodestruction of the bed of excised tumor. It was performed in the case of non-radical or conventionally radical operation for mitigation of the risk of a local recurrence.
6. Cryoapplication before organ mobilization. It was performed for exclusion of dissemination at mechanical destruction of a tumor in the process of its mobilization. Thereafter, a radical operation was performed.

Cryoapplication in case of pancreas body and pancreas tail cancer

The cryosurgical treatment of distal tumors of pancreas was performed in 51 patients. Of these: 26 (50.95) were men, and 25 (49.1%) were women. The average age was 58±9.1, the minimum age was 29, and the maximum age was 71 years.

In 44 patients, pancreas tumors were not resectable: a tumor was deemed locally spread (appreciable retroperitoneal invasion, invasion of upper mesenteric vessels - in 18 patients, of celiac trunk and its branches - in 9 patients, metastatic affection of the lymph nodes of regional lymph channel - in 3 patients, metastases to lymph nodes of mesentery root - in 5 patients), besides, liver metastases were revealed in 12 patients, abdominal metastases - in 2 patients, blastematic ascites - in 4 patients. 9 patients were in the IIA stage, 8 -patients - in the III stage, and 26 patients were in the IV stage of the tumor process.

Localization of the tumor process in the projection of pancreas body was observed in 14 (31.8%) patients, of pancreas body-tail - in 16 (36.4%) patients, of pancreas body-head - in 13 (29.5%) patients, and the total affection - in 1 (2.3%) patient. The convincing morphological verification at the preoperative stage was obtained in 45.6% of patients, doubtful - in 13.6% of patients, a tumor process was not verified in 9% of patient, and no verification was performed in 31.8% of patients. Pancreas duct adenocarcinoma was in 42 patients, pancreas cystadenocarcinoma was in 1 patient, and endocrinocellular cancer - in 1 patient.

The method of cryodestruction consisted in the following. Following laparotomy and decision on inoperability of the pancreas tumor, the tumor dimensions were determined (length and width), as well as the necessary dimensions of the tumor tissue freezing zone. The tumor depth was determined in the preoperative period by X-ray computer tomography. Following determination of dimensions and geometry of the intended cryodestruction zone, the ratio of cryoapplication cycles was determined, as well as location of the tumor with respect to the hollow organs, and the centers of application of cryoinstrument were determined. After it, the parameters of temperature and time conditions were selected, as well as the necessary dimensions of cryoapplicator. “Cryoelectronics-4(2)” apparatus was used for tumor freezing. The freezing was performed by direct contact method by way of placing cryoapplicator on the front tumor surface. Its temperature was set in the range from minus 170oC to minus 190oC, the time of a single exposure was from 10 to 25 minutes, and the diameter of cryoapplicator was from 20 to 50 mm. The last two parameters were chosen depending on the volume of tumor. We were the first to use a perforation applicator in the clinical practice. Its application was necessary if there was no confidence in complete destruction of tissue in the depth of neoplasm in the cases of large tumor dimensions. In a number of cases, cryoapplication was performed from two or three points. In some cases, cryoapplication was performed in two stages, with complete thawing and repeated cryodestruction in the same place. Cryodestruction was performed within the limits of sound tissues. The thawing was always spontaneous.

The study of activity of a-amylase of serum and transudate from abdominal cavity after cryodestruction revealed the following. During the first day following cryodestruction, the increase in activity of a-amylase of serum and transudate from abdominal cavity was 2.5 times and 2.1 times, respectively, as compared with the initial normal level. By the 5-th day after operation, the activity of a-amylase was brought to normal.

Of 44 patients that were subject to cryosurgical treatment for pancreas tumor, 3 patients died. Thus, the lethality rate was 6.8%. The reasons for lethality were as follows: acute hepatic insufficiency on the 7-th day after operation, acute cardiovascular insufficiency on the 2-nd day after operation, acute gastric ulcer bleeding on the 15-th day after operation. In pathologicoanatomic study of the data, pancreas inflammation was not observed; necrotized masses were observed in the tumor zone. However, the intact tumor tissue was observed around large blood vessels.

Taking into account more aggressive nature of duct adenocarcinoma as compared with cystadenocarcinoma and endocrinocellular cancer, we conducted a separate analysis of remote survival of duct adenocarcinoma cases.

The total survival in the group of patients with non-resectable distal-zone cancer of pancreas (only the cases with pancreas duct adenocarcinoma, excluding endocrinocellular cancer and cystadenocarcinoma) was 1 year - 11.8±5.1%, 2 years - 6.8±4.5%. Three-year’ survival was not observed. The median was 6 months.

The tumor recurrences or prolonged tumor growth are common after cryodestruction of pancreas tumor. The general idea is that the basis for tumor recurrences lies in restrictions of methodological nature connected with impossibility of achievement of the necessary temperature conditions in the immediate vicinity of large blood vessels and bowels, where vital tumor cells may survive as a consequence. In connection with it, the necessity arises in enhancing the destructive action of low temperatures on the tumor cells by way of combination of cryodestruction of pancreas tums with other treatment methods.

23 patients were subject to cryosurgical treatment only, 19 patients were subject to combined treatment (out of these: cryosurgery + radiation therapy - 10 patients, cryosurgery + chemotherapy - 9 patients).

The remote survival among the patients subject to cryodestruction alone of distal-zone cancer of pancreas was as follows: 1 year - 5.17 ± 3.35%. Two-year’ survival was not observed. The median was 5.8 months.

In the combined cryoradiation treatment, cryodestruction was supplemented by remote radiotherapy with 18-25MeV (18-25 МэВ) braking high-energy radiation performed by longitudinal method with prolonged course in the mode of dose superfractionation (ROD 2 g, SOD > 60 g), or by remote gamma-therapy in the similar doses. Radiation therapy was performed on the 10-12-th days following pancreas tumor cryodestruction, and if it was supported well, - without interruption. 3 more patients were not subject to complete course of radiotherapy , - the treatment was suspended at SOD < 40 g in consequence of side reactions in the form of general radiation reaction and radiation gastroenteritis developed in the process of treatment. The remote survival of the patients subject to cryosurgical treatment with subsequent radiation therapy was as follows: 1 year - 0%. The median was 6.7 months.

He remote survival of the patients subject to cryosurgical treatment with subsequent chemotherapy was as follows: 1 year - 25.0±14.4%, 2 years -25.±14.4% (survival of one patient in this group was 25 months). Three-year’ survival was not observed. The median was 9 months. The clinical observation of this patient is given below:

Patient C, 68 years old, was in the Liver and Pancreas Surgery Ward of Russian Oncological Center of RAMS from 21.12.04 to 12.01.05 with the following diagnosis:

Pancreas body cancer, T4NjM/, IVB stage
Since autumn of 2003, she had suffered from pain in epigastric zone. After the investigation in the policlinic, the pancreas body cancer was diagnosed (cytology No. 04/0568: adenocarcinoma). She was hospitalized to Liver and Pancreas Surgery Ward of Russian Oncological Center of RAMS. In the course of ultrasound investigation (USI, CT) and angiography, a pancreas body tumor was revealed with injury of celiac trunk and splenetic vessels. No other manifestation of the disease was revealed.

The patient was operated on 28.04.04. The following was established: 4×5 cm tumor of pancreas body with III hepatic lobe metastasis up to 2 cm. Taking dissemination of the tumor process into consideration, the decision was made to abstain from radical operation. Cryodestruction of pancreas tumor and atypic resection of hepatic lobe were performed. In histological examination, moderately differentiated liver metastasis of adenocarcinoma was diagnosed. The postoperation period was without complications. 6 courses of chemotherapy were conducted according to the following scheme: Gemzar - 1 g/m on the 1-st and 8-th days with 2 weeks’ interval.

In the control investigation in December 2004 (Ultrasonic study, MRT of abdominal cavity, and X-ray investigation of pectoral organs), no recurrences or metastases were revealed. However, the growth of tumor marker CA 19-9 from 45 ME/ml to 62 ME/ml was observed in October 2004. With regard to it, we decided to proceed with PCT according to the following scheme: Eloxatin 150 mg i/v with drop bottle on the 1 day, Gemzar 1.5 g i/v with drop bottle on the 1-st and 8-th days. The survival of the patient was 25 months after operation.

This case is of interest, because the originally disseminated patient with the exact morphological verification of the diagnosis has lived such a long time after cryodestruction. Its relation to chemotherapy only is problematic as other patients were subject to PCT with the use of the same medications without cryodestruction with much worse results.

The pancreas tumor cryodestruction was accompanied by a pronounced symptomatic effect: full release from pain - in 54.6% of patients, decrease of pain - in 38.6% of patients. No clinical effect of cryodestruction was observed in 6.8% of patients. The comparative data of analgetic effect in the use of different methods of treatment of non-resectable pancreas tumor cases are given in table 1.

Table 1. Analgetic effect in the use of different methods of treatment of non-resectable pancreas tumor cases

As evident from the data presented in the Table 1, the combined treatment has the most pronounced analgesia: within the period of 2-3 months, a stable analgesia is observed in all patients subject to cryoradiation treatment, which is positively higher than in the case of cryosurgical treatment.

After the conducted treatment, the survival of patients with non-resectable locally propagated cystadenocarcinoma and endocrinocellular cancer of pancreas body and tail is much higher. Thus, after cryosurgical treatment of locally propagated endocrinocellular cancer of pancreas, the survival of one patient was 39 months. The survival of a patient with cystadenocarcinoma of pancreas body and tail was 30 months.

The group of 44 patients with non-resectable tumors of pancreas distal zones was discussed above. Further, we’ll proceed with the analysis of the group of 7 patients with the tumors of pancreas distal ones, wherein cryoapplication was combined with a radical operation. 4 patients with duct adenocarcinoma and one patient with cystadenocarcinoma of pancreas body and tail were subject to distal subtotal resection with further cryodestruction of the tumor bed. The patient with cystadenocarcinoma of pancreas body-tail was subject to radiation therapy in the postoperation period in the mode of dose superfractionation of SOD 40 + 23 g, followed by chemotherapy. She died in 123 months following the operation. One patient with duct adenocarcinoma was subject to circular resection of UMV (upper mesenteric vein) with its further plastics with synthetic prothesis. The patient died in 3 months following treatment. The rest of the duct adenocarcinoma cases lived out 12, 8, and 4 months. The median was 6.75 months.

The last two patients were subject to cryodestruction of the pancreas body and tail at the first stage of surgical intervention, followed by distal subtotal resection of celiac trunk and edge resection of upper mesenteric vein. In the postoperation period, the radiation therapy was prescribed to the patient, which at SOD 8 u was suspended through a general radiation reaction. The patient died in 7 months following the operation. The second patient was subject to chemotherapy in the postoperation period. In the process of treatment, dissemination - lung metastases - were revealed. The patient is alive in the course of 20 months.

Cryoapplication in case of pancreas head cancer

In view of the risk of duodenum necrosis, a cryosurgical method as an independent method may not be used in the patients with pancreas head cancer. However, we used cryodestruction in respect of resectable pancreas head tumor for prevention of dissemination at mechanical damage of tumor in the process of its mobilization. Thereafter, a standard resection of pancreas head tumor was performed.

Such scheme was applied in 2 patients. These patients had a moderately differentiated adenocarcinoma of pancreas head. Both patients were in the IV-th stage of the disease as a result of local tumor dissemination (invasion into duodenum wall, retroperitoneal invasion, upper mesenteric vein invasion of B type.). Following tumor cryodestruction, pancreatoduodenectomy was performed. At that, resection of vessels was performed in both cases: in the first case - circular resection of upper mesenteric vein, in the second case - resection of upper mesenteric vein/upper vein. The clinical observation of the first patient is given below:

Patient A, 65 years old, was in the Liver and Pancreas Surgery Ward of Russian Oncological Center of RAMS in April 2003 with the following diagnosis: pancreas head cancer, T4 N1 MO, IV A stage.

In January 2003, loose stools appeared, the patient went down by 12 kg. In the course of domiciliary examination, a bulk neoplasm of pancreas head was revealed. The patient was sent to the Russian Oncological Center of RAMS. In the course of ultrasound investigation (USI) MRT and angiography, a pancreas head tumor node was revealed, dimensions 3.1×2.7×2.5 cm, with increased parapancreatic lymph nodes. In needle cytobiopsy of the node, the cells of adenocarcinoma were revealed. No icterus was observed, C A-19-9 3169,0.

The patient was operated on 25.04.03. . The following was established: 3×4 cm tumor of pancreas head with a conglomerate of soft-consistency lymph nodes palpated in the mesentery root. No liver or abdominal metastases were revealed. No ascites was revealed. The gall bladder 7×4 cm was moderately strained. Gastropancreatoduodenectomy was performed with prior cryodestruction of pancreas head tumor and circular resection of upper mesenteric vein. Histological study of the resected complex: the tumor in the pancreas head had the structure of a moderately differentiated adenocarcinoma, with metastases in the back pancreatoduodenal lymph nodes being of the same structure. In 4 months following the operation, propagation of the process, with metastases to peritoneal lymph nodes, was revealed. Gemzar chemotherapy was prescribed, which was performed in the course of one year. Against this background, a regress of peritoneal lymph nodes was observed. Chemotherapy was suspended. The patient was under dynamic observation. In the course of control examination in May 2006, a metastasis to L5 vertebra was revealed. No other tumor changes were revealed. Chemoradiation therapy was prescribed. The patient is alive in the course of 37 months.

At present, practically all patients with pancreas head cancer are subject to adjuvant chemotherapy with the use of advanced medications (Gemzar) following radical surgical treatment in the scope of resection of pancreas head. However, far from all patients have such pronounced results following cryodestruction and conventionally radical operation as in the above-described case.

The second patient did not receive any additional treatment. His survival was 22 months.

Thus, pancreas tumor cryodestruction is relatively safe, efficient, controllable, and has a sufficient destructive affect. The advantages of this method are as follows: biological inertness of cryonecrosis nidus and simplicity of the method. It is also known for its clinical efficiency: analgetic effect and increase in lifetime. Cryodestruction of pancreas tumors may be combined with other methods of treatment.

Alongside with the aforementioned, the role and importance of the cryosurgical methods in treatment of patients with biliopancreatoduodenal zone tumors is still to be studied. The given examples of highly-efficient treatment of the pancreas duct cancer, including cryosurgical effect on tumors, were observed in single patients. It may be more the evidence of biological peculiarities of certain tumors and individual immunobiological characteristics of certain patients than of efficiency of the treatment as such. Besides, the observations of successful treatment of pancreas duct cancer were observed in the cases of using cryodestruction in combination with its surgical excision, and cryodestruction with further cytostatic chemotherapy. In connection with it, the following studies have been conducted in our clinic: study of prognostic role of a number of molecular-genetic factors in pancreas duct cancer patients, who were subject to cryosurgical treatment; study of the role of cryosurgical treatment in combination with surgical treatment and combined method of treatment of pancreas duct cancer patients etc. Following their completion, the clinical oncology will acquire the new knowledge indispensable in the practice of treatment of Pancreas Duct cancer patients.