[Irreversible electroporation in locally advanced pancreatic cancer]. / Neobratimaya elektroporatsiya pri mestno-rasprostranennoi adenokartsinome podzheludochnoi zhelezy.

OBJECTIVE: To determine the feasibility of irreversible electroporation (IRE) for locally advanced pancreatic adenocarcinoma. MATERIAL AND METHODS: Twenty-three patients underwent IRE after chemotherapy for locally advanced pancreatic cancer between 2015 and 2022. IRE was performed during laparotomy as a rule (n=22). In one case, IRE was combined with palliative pancretoduodenectomy. Nineteen (86.3%) patients received adjuvant chemotherapy after the procedure. The follow-up examination included contrast-enhanced CT/MRI of the abdomen, chest X-ray or CT, analysis of CA 19-9 marker one month after surgery and then every three months. RESULTS: Complications after IRE developed in 5 (21.7%) patients. Three patients (13.0%) had arrhythmia, two (8.7%) ones had pancreatic necrosis. A 90-day mortality after the procedure was 4.3% (n=1), the cause was pancreatic necrosis. According to intraoperative data and the first examination (CT/MRI), the entire tumor infiltrate was treated in 21 (91.3%) cases. Median follow-up was 19 months. Median period until local recurrence was 15 months. Isolated local recurrence was observed in 7 patients. Of these, 3 ones underwent radiotherapy, one patient underwent repeated IRE. Distant metastases were found in 11 patients; systemic therapy was restarted. Median time to progression was 7 months after IRE and 14 months after initiation of chemotherapy. The median overall survival was 16 months after electroporation and 25 months after chemotherapy. CONCLUSION: Irreversible electroporation may be useful in carefully selected patients with unresectable locally advanced pancreatic adenocarcinoma after successful induction chemotherapy. This procedure provides local control, but the impact on long-term outcomes and feasibility of routine use should be analyzed in randomized trials.

[The role of molecular genetic factors in the development of cholangiocellular carcinoma]. / Rol' molekulyarno-geneticheskikh faktorov v razvitii kholangiotsellyulyarnogo raka.

The article lists the main inducers of cholangiocarcinogenesis. The main inflammatory mediators (IL-6, nitric oxide, COX2) have been considered. Data on the study of gene mutations in cholangiocarcinomas are presented. The spectrum of genetic mutations depends on the biliary cancer origin (FGFR2 with intrahepatic cholangiocarcinoma, PRKACA, PRKACB with extrahepatic cholangiocarcinoma). Mutations in the KRAS, TP53, ARIAD1A genes are common in extrahepatic bile duct cancer. The role of epigenetic changes such as DNA hypermethylation, histone modifications, chromatin remodeling, as well as disturbances in miRNA expression is presented. A number of epigenetic features, such as the presence of a TP53 mutations with hypermethylation of p14ARF, DAPK, and/or ASC, correlate with a more aggressive course of the disease. The role of the SOX17 gene in the development of drug resistance is highlighted. The study of the molecular genetic features of extrahepatic bile duct cancer can help to better understand the pathogenesis of this type of tumor, to establish new prognostic and diagnostic markers of the disease.

[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.

[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.

[The possibilities of surgical treatment of hepatocellular cancer in patients with liver cirrhosis].

154 radical liver resections were performed on the reason of the hepatocellular cancer, of them 33% in patients with liver cirrhosis. Liver function was assessed using the Child--Pugh score. Liver cirrhosis and extensive liver resections proved to be the independent complication and lethality risk factors. The extensive liver resections were performed in 70%. The postoperative morbidity rate was 44.8%, the lethality was 5.8%. The concomitant liver cirrhosis reliably worsens postoperative complications (p = 0.001) and lethality (p = 0.0001) rates. The long-term treatment results were analyzed. Thus, liver resection proved to be an appropriate treatment for patients with hepatocellular cancer and liver cirrhosis Child--Pugh stage A, but a thorough patient selection is recommended. Liver resection is contraindicated by liver cirrhosis Child--Pugh stage B. The orthotopic liver transplantation is recommended in such cases, considering that Milan criteria are observed. The rest cases should consider the possibilities of radiofrequency ablation, transarterial chemoembolization, chemotherapy.

[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.

[Liver resection in locally-spread and metastatic kidney cancer]. / Rezektsii pecheni pri mestno-rasprostranennom i metastaticheskom rake pochki.

The postoperative outcome and survival were studied in patients operated for renal cancer with involvement of the liver. 9 patients have undergone radical nephrectomy and 12 patients--hepatic resections for direct hepatic involvement (2), synchronous (2) and metachronous (8) metastases of renal cell carcinoma. Right hemihepatectomy was performed in 2 and wedge resection in 10 cases. A complete resection was performed in 8 of 9 patients while one patient with direct hepatic invasion was found to have positive surgical margins. Postoperative lethality was absent but complications occurred in 6 patients: pancreatitis (1), pneumonia (3), hepatic abscess (1), hepatic and renal failure followed by GI bleeding (1). At follow-up, two patients died of progressive disease 4 and 68 months after the surgery and one was lost for follow-up. One patient with positive surgical margins is alive with pulmonary and liver metastases 16 months after surgery. Five patients are alive with no evidence of relapse 6, 10, 12, 19 and 56 months after the operation. Thus, the aggressive surgical approach is justified and should be considered in patients with renal cancer and hepatic involvement.

[Hepatopancreatoduodenal resection in locally advanced cancer of gallbladder]. / Gepatopankreatoduodenal'naia rezektsiia pri mestnorasprostranennom rake zhelchnogo puzyria.

A case of hepatopancreatoduodenectomy in advanced cancer of the gall bladder is presented as well as literature data on indications for this operation, technical peculiarities of its performance, postoperative complications, follow up results and advisability of carrying out such a complicated surgical intervention.