[Cholangiocellular cancer: the state of the problem and ways to improve the results of surgical treatment]. / Kholangiotselliuliarnyi rak: sostoianie problemy i puti uluchsheniia khirurgicheskogo lecheniia.

AIM: To improve the outcomes in patients with resectable biliary cancer. MATERIAL AND METHODS: There were 263 procedures for cholangiocellular carcinoma (CCC) for the period 1998­2017. Adjuvant chemotherapy was performed in 102 (38.8%) patients. Extensiveliver resections (78.9%) prevailed for intrahepatic cholangiocellular carcinoma (n=128), 6 (4.7%) patients required vascular resection. Seventy-seven pancreatoduodenectomies were performed for common bile duct cancer, portal vein resection was done in 8 (10.4%) patients. In case of Klatskin tumor (n=58) liver resection combined with bile duct resection (n=52) prevailed. Portal vein resection was done in 16 (27.6%) patients. RESULTS: Postoperative morbidity in patients with intrahepatic CCC was revealed in 68 (53.1%) cases, mortality ­ in 5 (3.9%) cases. Among patients with Klatskin tumor morbidity was revealed in 51 (87.9%) cases, mortality ­ in 6 (10.3%) cases. In patients with common bile duct cancer morbidity was revealed in 53 (68.8%) cases, mortality ­ in 4 (5.2%) cases. In whole cohort median overall survival was 30 months. R0-resection was associated with better long-term results (median 37 months) compared with R1­R2 resection (20 months; p=0.01). Lymph node involvement is associated with significantly worse prognosis (p=0.016), however 5-year survival is observed (25.6%). Adjuvant chemotherapy in R0-resection significantly improved long-term results: median was 46 months (vs. 30 in group without chemotherapy; p=0.02). In intrahepatic CCC patients multiple lesions or mechanical jaundice did not aggravate long-term results. CONCLUSION: R0-resection including lymphadenectomy, resection of adjacent organs and vessels is advisable for CCC. Isolated bile duct resection should be used as an exception. Adjuvant therapy improved long-term results. Multiple lymph node lesion or bile duct infiltration are not contraindications to surgery in intrahepatic CCC patients.

Surgical and combined treatment of patients with Klatzkin's tumor.

Surgery as being a preferential method of treatment of patients with cholangiocarcinoma is associated with high complications and mortality levels while demonstrating poor long-term outcomes. Optimization of preoperative management and improvement of the results of surgical treatment for patients with proximal extrahepatic bile duct carcinoma. From January 1998 to December 2013 surgical treatment was performed in 36 patients (19 males, 17 females) with Klatzkin's tumor, from whom 10 patients obtained postoperative chemotherapy. Bismuth-Corlette type III-IV tumor stage was determined in 30 (83.3%) patients. Portal vein resection was performed in 13 (36.1%) patients. 27 (75.5%) patients underwent R0 resection. Postoperative mortality rate consisted 16.7%, complications were revealed in 87.1% of cases. 6 (16.7%) patients required additional surgery and interventional procedures were performed in other 20 (55.5%) patients to fix postoperative complications. Overall 5-year survival rate in R0-resection group was 40.1%, median - 29 months. In postoperative chemotherapy group overall 3-year survival rate was 66.7% which was twice higher than in surgery group but the difference was not statistically significant (p=0.35). The improvement of short-term outcomes of surgical treatment for patients with Klatzkin's tumor requires optimization of preoperative management and detailed adherence of surgical techniques. Combination of surgery with postoperative chemotherapy showed the trend to improvement of overall survival.

[Results of the repeated hepatic surgery on the reason of malignant tumors].

The work is based on an analysis of 95 clinical observations of patients with primary and metastatic liver disease who were in the surgical department of tumors of the liver and pancreas of the State Research Institute named by N.N. Blokhin of RAMS from 1990 to 2011. All patients underwent two or more liver resections. Of all 95 patients included in this study, 64 underwent repeated interventions over a liver colorectal metastases. 10 patients had the operations, which were performed for primary hepatocellular carcinoma of the liver. In 21 patients re-resection were performed for metastatic lesions of other tumor nosology. Postoperative mortality in tumor lesions of the liver in patients who underwent repeat resection was 1.05%, postoperative complications occurred in 38.9% of patients. All patients with colorectal liver metastases who underwent repeat resection of various sizes, five-year survival rate was 53.3±8.8%. Median 35.9 months. The low level of mortality and acceptable level of postoperative complications in patients re-operated liver tumor, as well as high rates of long survival confirm the thesis about the need for such interventions as part of combined treatment of this difficult group of patients.

[Surgical treatment of hepatocellular carcinoma].

Experience of surgical treatment of 171 patients, suffering hepatocellular carcinoma (HCC), was summarized. Extensive hepatic operations were performed in 99 (71.2%) patients, of them in 22.2%--on the concurrent hepatic cirrhosis background. Late results of treatment, depending on the main prognostic factors present, were analyzed. Cumulative survival in the terms of 5, 10 and 20 years have constituted 53.5, 37.3 and 28.8% accordingly. Accomplishment of a radical hepatic resection for HCC permits to achieve a durable remission of a tumoral process. While revealing a concurrent hepatic cirrhosis stage B (according to Child--Pugh classification) it is appropriate to use a hepatic transplantation and other methods of treatment, including chemoembolization, radiofrequency ablation, chemotherapy.

[The prognostic value of tumor cells blood circulation after liver surgery for cancer lesions].

The study aimed to prove the prognostic meaning of micrometastases blood circulation during liver resections for cancer lesions. 33 patients took part in the study. Circulating micrometastases were detected in blood using immunocytological method with pancytoceratine antibodies KL-1 and CAM 5.2. The majority of patients had colon cancer liver metastases (72,7%). Blood was sampled once in 8 patients, the rest 25 patients had double sampling: before and after liver mobilization. Patients with multiple liver metastases demonstrated tumor cells circulation more often. Of 58 tests, 25 were positive for tumor cells. 3-year survival in those patients was 45,7 ± 13,1%, 5-year survival was 24,4 ± 13,3%. Survival rates for patients with no circulating tumor cells detected were significantly higher.

[Surgical and combined treatment of patients with metastatic liver and lymph nodes invasion by colorectal cancer].

527 patients were operated on for liver colorectal cancer metastases. Of all cases of lymphadenectomy during liver resections, lymph nodes invasion was morphologically proved in 43 patients. 3- and 5-year survival rate in this group was 12,8+/-6.6% and 6.4+/-5.6%, respectively. No patients survived a ten-year interval. Maximal follow-up period was 62 months, median - 17 months. 3-year disease-free survival rate was 5.1+/-4.8%. No 5-year disease-free survival was registered. Inclusion of oxaliplatin in adjuvant chemotherapy regimen allowed the dramatical improvement of survival rates.

[Advanced hepatic resection for malignancy].

125 patients with hepatic neoplasms were observed during 1998-2008 years. Trisectionectomy was carried out to 84 patients with colorectal metastatic affection of liver, which amounted 67.2% of all cases. Hepatocellular carcinoma was the second most frequent malignancy to be observed--23 patients (18.4%). 6 patients (4.8%) with cholangiocellular carcinoma went further. 12 patients (9.6%) with non-colorectal metastatic tumors of liver were united into one group. In postoperative period adjuvant chemotherapy was carried out to 60 patients with colorectal metastatic affection of liver. In all patients with hepatic tumors undergoing trisectionectomy postoperative lethality amounted 6.4% (n=8), in patients with colorectal metastatic affection of liver--5.95% (n=5), in patients with primary hepatic tumors--3.45% (n=1), in patients with non-colorectal metastatic affection of liver--16.66% (n=2). Lethality was caused by acute hepatic failure in all observations. Postoperative complications were observed in 44.05% of patients with colorectal cancer and in 44.83% of patients with primary hepatic tumors. Hepatic failure was the most frequent complication. In case of colorectal metastatic affection three-year probability of survival amounted 30.94+/-6.6% in patients undergoing trisectionectomy, five-year--10.4+/-8%. Median 16 months. On conditions that adjuvant chemotherapy was carried out, three-year survival probability increased to 40.53+/-8.1%, five-year--to 10.4+/-8%. Median 17 months. One-year survival probability in patients with primary hepatic tumors undergoing trisectionectomy amounted 92.46+/-5.1%, three-year - 59.44+/-12.3%, five-year--44.58+/-15.8%. Median 42 months. Low level of postoperative lethality, allowable level of postoperative complications and good indices of survival probability in long-term period allow considering that trisectionectomy as a surgical technique is absolutely appropriate.

[The combined treatment of colorectal cancer with liver metastases].

The direct and follow-up results of surgical and combined treatment of colorectal cancer with liver metastases are presented. Complication rate after liver resections was 28.4% and lethality was 3.5%. Follow-up results evidence the decrease of survival in patients with adjuvant chemotherapy after surgery. The safety of oxalyplatin in patients after liver resections, including its intraarterial infusion through the hepatic artery is shown. Oxalyplatin-based chemotherapy regimen tended to be more effective in comparison with 5-fluorouracil scheme, especially in patients with synchronous or multiple liver metastases. Considering that the difference is not statistically significant, further studies of oxalyplatin influence on survival of patients with colorectal liver metastases are necessary.

[Multivisceral resections at disseminated abdominal tumors].

Overall 131 multivisceral resections at disseminated abdominal malignant tumors have been performed. The main arguments to extended operations were local dissemination of tumor (35.1%), synchronous hepatic metastases (49.6%), combination of local dissemination with synchronous metastases (6.1%), isolated synchronous tumors (6.1%), and multiple metastases with polyorganic localization (3%). The rate of postoperative complications and lethality at the patients undergone multivisceral operations were 34.3 and 6.8% respectively. There were no significant differences in postoperative complications rate and lethality between adjusted multivisceral and standard operations groups.

[Synchronous operations in metastatic cancer of the liver].

The resection of the liver has been performed in 661 patients including 154 (23.3%) cases of synchronous metastatic cancer of the liver. Among the latter patients primary tumor was removed in one stage with liver resection in 56% cases. Elderly age of the patients, multiple bilobular foci in the liver, size of the foci more than 10 cm, traumatic operations on the primary focus were not contraindications to synchronous operations. Surgical treatment for colorectal cancer should be supplemented with adjuvant chemotherapy. The long-term results demonstrate better survival after synchronous operations for colorectal cancer.

[Liver cancer: immunohistochemical and electron microscopic study].

Primary liver tumors, including 7 low-grade hepatocellular carcinomas (HC), 12 average-grade HC (including 2 mixed tumors and 2 cholangiocellular carcinomas (ChC)), obtained from 23 patients, were histologically, immunohistochemically, and electron microscopically. Certain markers were immunohistochemically studied to identify HC and ChC and differentiate liver carcinoma from metastatic tumors of the same organ.

[Surgical and combined treatment of multiple and bilobar metastatic affection of the liver].

Short- and long-term results of surgical treatment in combination with local exposures (cryo- and thermo-destruction) and adjuvant chemotherapy in patients treated for multiple and bilobar metastatic affection of the liver were studied. Postoperative lethality was 2,5% (n=2) due to liver insufficiency. Specific for liver resection complications (bile outflow, moderate hepatic failure) do not exceed 20,5%. Five-year survival of patients with solitary bilobar metastatic affection of the liver (not more than two foci) was 39,1+/-14,3%. This demonstrates that solitary bilobar hepatic metastases is not a negative prognostic factor for surgical treatment. Long-term results of treatment of patients with multiple metastases of colorectal cancer to the liver are worse, but 1-, 2-, and 3-year survival demonstrates validity of surgical policy in treatment of these patients. Postoperative chemotherapy significantly improves long-term survival of patients with multiple or/and bilobar metastases of colorectal cancer to the liver.

[Ways to improve tolerance to gastro-pancreatic-duodenal resection]. / Puti uluchsheniia perenosimosti gastropankreatoduodenal'noi rezektsii.

Immediate results of 125 gastropancreatoduodenal resection (GPDR) performed for cancer of the pancreatoduodenal zone are presented. Despite extended surgery volume (15 GPDR were extended, in 14 patients resection of the major vessels was performed) postoperative lethality decreased to 1.6% due to lowered rate of severe postoperative complications (first of all insufficiency of pancreato- and biliodigestive anastomosis). Ways of prophylaxis of these complications consist in conduction of percutaneous puncture transhepatic cholangiostomy as the method of choice for billiary decompression before surgery in patients with tumor obstructive jaundice, precise surgical technique, creation of pancreatogastroanastomosis on reconstructive stage of GPDR.

[Extended gastropancreatoduodenal resection (GPDR)]. / Rashirennaia gastropankreatoduodenal'naia rezektsiia.

The authors for the first time in Russia have begun serial performance of the extended GPDR. The operations were accompanied by careful morphological investigations of the removed organs and tissues. It was established that in all patients with exocrine cancer of head of the pancreas the tumor growth extended the region of the regional lymph nodes, i.e. standard GPDR in these patients oncologically could not be considered as adequate operation. Further performance of GPDR for pancreatic head exocrine cancer will expand knowledge about metastatic spread and will open opportunities to improve long-term survival of the patients with exocrine cancer of the head of the pancreas.

[Repeated resection of liver in primary and metastatic cancer]. / Povtornye rezektsii pecheni pri pervichnom i metastaticheskom rake.

164 operations for malignant tumors of the liver were performed in Cancer Research Center. 14 patients underwent repeated resections of the liver, 5 of them due to primary cancer of the liver and 9--with metastatic liver disease. Recurrence was revealed in 6 from 14 patients (42.8%), within a year after resection, in 4 (28.6%)--during two year after the first resection of the liver. In the rest 4 patients (28.6%) recurrence was revealed after two and more years. The indications for repeated resections were: recurrent cancer in the liver which should be localized, with absence of extrahepatic metastasis, good functional condition of the liver and absence of concomitant diseases. Repeated resections of the liver are technically more complicated due to the following causes: functional condition of the liver is rather deteriorated, especially after previous extended resections; anatomical interrelations are disturbed, there are intensive adhesions. There were no lethal outcomes after repeated resections of the liver. 3 years survival of operated patients was higher (60%) than in patients who underwent resection of the liver once, both in a primary cancer of the liver (46.8%) and in metastatic cancer (40%).

[Current approaches to surgical treatment of liver tumors]. / Sovremennye podkhody k khirurgicheskomu lecheniiu opukholei pecheni.

Since 1990, 230 operations for focal pathologies in the liver have been carried out at the Center's clinics using such advanced procedures and equipment as radio-isotope examination of hepatic function, ultrasonography of the liver during surgery, ultrasound aspirator, water-flow scalpel, argon coagulator and adhesive dressing materials. The study included 75 resections for primary hepatic tumor (lethality-14.6%), 114 resections-disseminated tumor (lethality-5.2%) and 41 resections for benign tumors and non-tumor pathologies (no lethality). Preoperative chemotherapy was found to significantly increase the risk of postoperative complications in cases of liver resection. Five-year survival in such patients with primary tumor was 33.3%. The seven most significant prognostic factors in primary hepatic carcinoma were: portal invasion by tumor cells, number of tumor nodes in the liver, alpha-fetoprotein concentration, tumor node size, concomitant cirrhosis, age and extent of surgery. In patients with hepatic resection for solitary metastasis of the large bowel, 5-year survival was 28.6%. A regimen of adjuvant chemotherapy for solitary metastasis of colorectal cancer into liver is suggested. The data on 37 surgical patients with hepatic metastasis of non-colorectal cancer are presented. It was demonstrated that the liver should be resected in cases of solitary metastasis of renal carcinoma, adrenal gland, ovary, tests, breast, gallbladder and carcinoid.

[Hepatitis E in a nonendemic region: antibodies to hepatitis E virus in various groups of residents]. / Gepatit E v neéndemichnom raine: antitela k virusu gepatita E v razlichnykh gruppakh naseleniia.

Increase in the number of seropositive subjects in the population of European and North-American regions not endemic for hepatitis E stimulated research in this field. This study was aimed at investigating the incidence of IgG antibodies to hepatitis E virus (anti-HEV-IgG) in subjects with different liver diseases and in groups at increased risk of infection in a nonendemic region. In patients with different diseases of the liver the incidence of anti-HEV-IgG varied from 5.1 to 14.3%, in medical workers and former blood donors not allowed to donate blood because of increased transaminase levels in the blood 5.1 and 5.3%, respectively. In the reference group this level was appreciably lower-only 1.8%, this being rather close to the incidence of anti-HEV-IgG in the population of a nonendemic region (2.1%). There were no seropositive women in the group of healthy pregnant women in a non-endemic region, whereas in an endemic region (in Kyrghyzstan) 15% of pregnant women were seropositive for anti-HEV.

[The role of alpha-tocopherol and retinol in correcting disorders of lipid peroxidation in patients with malignant liver neoplasms]. / Rol' al'fa-tokoferola i retinola v korrektsii narushenii perekisnogo okisleniia lipidov bol'nykh so zlokachestvennymi opukholiami pecheni.

Patients with liver tumors are known to reveal antioxidant system disorders which lead to accumulation of products of lipids peroxidation and lower resistance. Levels of malonic dialdehyde as well as the antioxidant system (superoxide dismutase, catalase, alpha-tocopherol and retinol) in liver and tumor have been followed in 28 patients in whom liver was removed to treat malignant tumors. Liver and tumor tissue were shown to contain more dialdehyde and less superoxide dismutase and catalase than in the livers of accident victims. Treatment with alpha-tocoferol (600 mg), retinol (100,000 MU) and ascorbic acid (1.5 g) for 7 days before surgery was found to significantly reduce dialdehyde level in the liver. Also, the catalase level increased. Treatment with alpha-tocoferol and retinol resulted in their selective accumulation in the liver. No changes in lipid peroxidation or accumulation of alpha-tocoferol in tumor were recorded. Purulent and septic complications were 1.6 times less frequent after preoperative antioxidant treatment than in controls. It is recommended that said antioxidant treatment should be used to correct lipid peroxidation and to improve the effectiveness of therapy of liver cancer.