[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.

[Resection of liver segments VII-VIII: is right hepatic vein reconstruction advisable?] / Rezektsiya VII­VIII segmentov pecheni: est' li tselesoobraznost' rekonstruktsii pravoi pechenochnoi veny?

OBJECTIVE: To improve the treatment outcomes in patients with primary and metastatic liver tumors localized in segments VII-VIII involving the right hepatic vein and its branches. MATERIAL AND METHODS: There were 16 surgical interventions including resection of liver segment VII and/or VIII with resection of the right hepatic vein and its branches without reconstruction. All procedures were carried out at the Department of Liver and Pancreatic Tumors of the Blokhin National Medical Cancer Research Center for the period 2016-2020. The cause of surgery was colorectal cancer liver metastases in 8 patients, hepatocellular carcinoma in 2 cases, angiomyolipoma in 1 case and metastases of uterine cancer in 1 patient. Minor liver resection was additionally performed in 5 cases. RESULTS: Median surgery time was 150 (80-220) min, intraoperative blood loss - 400 (100-2000) ml. Afferent blood flow was blocked in 4 patients for 14 (12-25) min. None patient had intraoperative signs of impaired venous outflow. Biliary fistula in postoperative period occurred in 1 patient. No complications were noted in other cases. Median postoperative hospital-stay was 13 (9-19) days. There were no specific complications in long-term postoperative period that could be associated with venous outflow blockade through the right hepatic vein. CONCLUSION: Existing vessels and intrahepatic collaterals de novo can provide adequate venous outflow into the middle hepatic vein and short hepatic veins during resection of liver segments VII and/or VIII with resection of the right hepatic vein and its branches without reconstruction and the absence of inferior right hepatic vein.

Cytogenetic effects of low-dose radiation with different LET in human peripheral blood lymphocytes.

Chromosome damage and the spectrum of aberrations induced by low doses of gamma-irradiation, X-rays and accelerated carbon ions (195 MeV/u, LET 16.6 keV/microm) in peripheral blood lymphocytes of four donors were studied. G0-lymphocytes were exposed to 1-100 cGy, stimulated by PHA, and analyzed for chromosome aberrations at 48 h post-irradiation by the metaphase method. A complex nonlinear dose-effect dependence was observed over the range of 1 to 50 cGy. At 1-7 cGy, the cells showed the highest radiosensitivity per unit dose (hypersensitivity, HRS), which was mainly due to chromatid-type aberration. According to the classical theory of aberration formation, chromatid-type aberrations should not be induced by irradiation of unstimulated lymphocytes. With increasing dose, the frequency of aberrations decreased significantly, and in some cases it even reached the control level. At above 50 cGy the dose-effect curves became linear. In this dose range, the frequency of chromatid aberrations remained at a low constant level, while the chromosome-type aberrations increased linearly with dose. The high yield of chromatid-type aberrations observed in our experiments at low doses confirms the idea that the molecular mechanisms which underlie the HRS phenotype may differ from the classical mechanisms of radiation-induced aberration formation. The data presented, as well as recent literature data on bystander effects and genetic instability expressed as chromatid-type aberrations on a chromosomal level, are discussed with respect to possible common mechanisms underlying all low-dose phenomena.

[Cytogenetic effects of low dose radiation with different LET in human peripheral blood lymphocytes and possible mechanisms of their realization].

The induction of chromosome damage by the exposure to low doses of gamma-(60)Co and accelerated carbon ions 12C in peripheral blood lymphocytes of different donors was investigated. The complex nonlinear dose-effect dependence at the range from 1 to 50-70 cGy was observed. At the doses of 1-5 cGy the cells show the highest radiosensitivity (hypersensitivity), mainly due to the chromatid-type aberration, which is typical to those spontaneously generated in the cell and believed not to be induced by the irradiation of unstimulated lymphocytes according to the classical theory of aberration formation. With the increasing dose the frequency of the aberrations decreases significantly, in some cases up to the control level. At the doses over 50-70 cGy the dose-effect curve becomes linear. The possible role of the oxidative stress, caused by radiation-induced increase in mitochondrial reactive oxigen species (ROS) release in the phenomenon of hypersensitivity (HS) at low doses is discussed as well as cytoprotective mechanisms causing the increased radioresistance at higher doses.

[Induction of chromosome aberrations and micronuclei in human peripheral blood lymphocytes at low dose of radiation].

The chromosome damage induced by the doses of y-irradiation 6)Co in peripheral blood lymphocytes was studied using different cytogenetic assays. Isolated lymphocytes were exposed to 0.01-1.0 Gy, stimulated by PHA, and analysed for chromosome aberrations at 48 h postirradiation by metaphase method, at 49 h--by the anaphase method, at 58 h by micronucleus assay with cytochalasin B and, additionally, micronuclei were counted at 48 h on the slides prepared for the metaphase analysis without cytochalasin B. Despite of the quantitative differences in the amount of chromosome damage revealed by different methods all of them demonstrated complex nonlinear dose dependence of the frequency of aberrant cells and aberrations. At the dose range from 0.01 Gy to 0.05-0.07 Gy the cells had the highest radiosensitivity mainly due to chromatid-type aberration induction. With dose increasing the frequency of the aberrant cells and aberrations decreased significantly (in some cases to the control level). At the doses up to 0.5-0.7 Gy the dose-effect curves have become linear with the decreased slope compare to initial one (by factor of 5 to 10 for different criteria) reflecting the higher radioresistance of cells. These data confirm the idea that the direct linear extrapolation of high dose effect to low dose range--the procedure routinelly used to estimate genetic risk of low dose irradiation--cannot be effective and may lead to underestimation of chromosome damage produced by low radiation doses. Preferences and disadvantages of used cytogenetic assays and possible mechanisms of low ionising radiation doses action were discussed.

[Cytogenetic effects of low doses of radiation in mammalian cells: analysis of the hypersensitivity phenomenon and induced resistance]. / Tsitogeneticheskie éffekty malykh doz oblucheniia v kletkakh mlekopitaiushchikh: analiz fenomena giperchuvstvitel'nosti i indutsirovannoi rezistentnosti.

The induction of cytogenetic damage after irradiation of chinese hamster cells and human melanoma cells within a dose range 1-200 cGy was studied. The anaphase and metaphase analysis of chromosome damage and micronuclei test were applied. The hypersensitivity (HRS) at doses below 20 cGy and the increased radio-resistence at higher doses (IR) were shown with all cytogenetic critheria for both cell lines. The phenomenon of HRS/IR was reproduced in synchronic as well as in a synchronic population of chinese hamster cells. This fact shows that HRS was caused by high radiosensitivity of all cells and can not be explained by any differential sensitivity of cells in different phase of the cell cycle. So it was supposed that the increasing radio-resistence is determined by the inclusion of the inducible repair processes in all cells. This conclusion consents with the facts, that there was no evidence of HRS on dose-effect curves and that some parts of pre-existent damage was repaired after preliminary irradiation with low doses (1-20 cGy) which induce repair processes. It can be concluded that same inducible repair processes an analogous in mechanisms underlying in the base of HRS/IR phenomenon and adaptive response.

[Recovery of the viability of Chinese hamster V79-4 cells after combined exposure to hyperthermia and radiation]. / Vosstanovlenie zhiznesposobnosti kletok kitaiskogo khomiachka V79-4 posle kombinirovannogo vozdeistviia gipertermii i radiatsii.

The survival of cells overheated (42 degrees C) before gamma irradiation is increased by holding them in the growth medium at 37 degrees C before treatment with hypertonic NaCl solution. The substantial synergistic effect of hyperthermia and radiation takes place when the cells are treated with a 1.5 M NaCl solution immediately after the combined action of these inactivating factors. The synergistic effect is decreased by holding the cells in the nutrient medium at 37 degrees C for 4 hours before hypertonic treatment.

[Yield of sister chromatid exchanges and survival of V79-4 Chinese hamster cells irradiated with 0.7 MeV neutrons]. / Vykhod sestrinskikh khromatidnykh obmenov i vyzhivaemost' kletok kitaiskogo khomiachka U79-4 pri obluchenii neitronami s énergiei 0.7 MéV.

The dependence of the survival rate and the number of sister chromatid exchanges (SCEs) in Chinese hamster V79-4 cells on the dose of gamma-rays and neutrons with average energy of 0.7 MeV has been investigated. The value of RBE for neutrons is 5.5. The number of SCEs increased with the dose of gamma-radiation while no induction of SCEs could be detected after neutron irradiation.

[Lethal action of accelerated heavy ions on mammalian cells as affected by inhibitors of DNA synthesis. A theoretical analysis]. / Letal'noe deistvie uskorennykh tiazhelykh ionov na kletki mlekopitaiushchikh v usloviiakh vliianiia ingibitorov sinteza DNK. Teoreticheskii analiz.

Günter-Schulz's model and the authors' own model were used to study the dependence of radiosensitivity (D0(-1)) of Chinese hamster cells on linear energy transfer (LET) upon irradiation in standard conditions and in the presence of DNA synthesis inhibitors, arabinosylcytosine and hydroxyurea. A better agreement of the experimental and theoretical results was obtained using Kozubek-Krasavin's model than the model of Günter and Schulz.

[Lethal action of accelerated heavy ions on mammalian cells as affected by inhibitors of DNA synthesis. Results of experimental research]. / Letal'noe deistvie uskorennykh tiazhelykh ionov na kletki mlekopitaiushchikh v usloviiakh vliianiia ingibitorov sinteza DNK. Rezul'taty éksperimental'nykh issledovanii.

Radiosensitivity of Chinese hamster cells exposed to 137Cs-gamma-radiation and accelerated heavy ions of 4He (L = 22 and 60 keV/micron), 12C (L = 231 keV/micron), and 20Ne (L = 690 keV/micron) was studied in standard conditions and in the presence of arabinosylcytosine and hydroxyurea. These agents were shown to exert a radiosensitizing effect in the case of gamma-radiation. The effect was less pronounced with 4He ion-radiation and was absent upon irradiation with 12C and 20Ne ions. The radiosensitivity was maximum upon irradiation with 4He ions at L = 60 keV/micron. The RBE coefficients of heavy ions under study decreased in the presence of DNA synthesis inhibitors.

[Effect of inhibitors of DNA synthesis on the sensitivity of mammalian cells to radiation with different levels of linear energy transfer]. / Vliianie ingibitorov sinteza DNK na chuvstvitel'nost' kletok mlekopitaiushchikh k deistviiu izluchenii s raznoi lineinoi peredachei énergii.

Radiosensitivity of Chinese hamster cells increased by 1.71 times in the presence of arabinoside cytosine and hydroxyurea after gamma-irradiation, and no sensitization occurred after irradiation with carbon ions of 6.6 MeV/nuclon (LET, 227 keV/micron). Under a standard set of conditions, the RBE coefficient of carbon ions decreased from 3.09 to 1.78 in the presence of DNA synthesis inhibitors. The possible mechanism of this phenomenon is discussed.