Igor B. Shchepotin

Extended surgical resection in T4 gastric cancer.

BACKGROUND Some physicians still consider invasion of adjacent organs by the carcinoma of stomach as a sign of incurable disease. METHODS This retrospective study has been done with particular reference to 353 T4 gastric cancer patients who underwent combined gastrectomies with adjacent organs. RESULTS Subtotal gastrectomy was performed in 237 (67.1%) patients and total gastrectomy was performed in 116 (32.9%) patients. Organs most commonly resected with the stomach were the transverse colon in 159 (45%) cases, the tail of pancreas and spleen in 150 (42.5%), the left lobe of liver in 101 (28.5%), and the head of pancreas in 37 (10.5%) patients. A total of 110 postoperative complications occurred in this subset of patients corresponding to a complication rate of 31.2%. A total of 48 postoperative deaths occurred in this subset of patients corresponding to a mortality rate of 13.6%. The 5-year survival rate for all patients who underwent combined gastrectomy with adjacent organs was 25%. Of the node-negative T4 gastric cancer resections, 37% survived 5 years whereas the T4 node-positive resections have only a 15% 5-year survival. CONCLUSIONS Patients who present with T4 gastric cancer (about 20% of the patient population) will benefit from aggressive en bloc surgical resection and should not be considered unresectable.

Intensive preoperative radiotherapy with local hyperthermia for the treatment of gastric carcinoma

In order to devitalize maximally tumour tissue and improve the prognosis of gastric cancer patients, a method employing preoperative intensive radiotherapy with local hyperthermia as adjuvant treatment was evaluated. In order to estimate the effectiveness of preoperative intensive radiation and radiation with local microwave hyperthermia in radical gastric cancer treatment, 293 patients were randomized into three respective treatment groups: surgery alone, surgery preceded by preoperative radiation; and surgery followed by preoperative radiation and hyperthermia. Preoperative radiation therapy to a total dose of 20 Gy in four 5 Gy fractions did not improve 3- or 5-year survival in gastric cancer patients in comparison with surgery alone. Local hyperthermia in combination with radiation therapy followed by surgery produced a significant improvement in 3-year survival of 22.1% (from 35.5 +/- 4.9% to 57.6 +/- 6.3%, P < 0.05) and 5-year survival of 21.3% (from 30.1 +/- 4.7 to 51.4 +/- 6.6%, P < 0.05). In unresectable gastric cancer patients, radiation therapy and radiation therapy with hyperthermia both increase mean survival. In conclusion; intensive preoperative radiation therapy in total dose 20 Gy plus local microwave hyperthermia significantly improved 3- and 5-year survival in comparison with surgery alone. Further development and evaluation of equipment to produce reliable and safe delivery systems for hyperthermia is needed.

Postoperative complications requiring relaparotomies after 700 gastrectomies performed for gastric cancer

BACKGROUND Prevention of fatal postoperative complications and improved management of patients with complications are important means of increased survival in gastric cancer patients. PATIENTS AND METHODS A study of 700 patients undergoing gastrectomy was performed to examine factors that contributed to a high rate of postoperative complications. RESULTS Of 700 patients undergoing gastrectomy for adenocarcinoma, 40 (5.7%) underwent reexploration because of serious complications. The frequency of the relaparotomies varied from 2.1% and 4.4% after regular subtotal and total gastrectomies, respectively, to 20% and 30.4% after palliative and conventional total gastrectomies, respectively. The complications that required reexploration most frequently were anastomotic leakage and incompetence of sutures (11, 27.5%), intra-abdominal abscesses (8, 20%), and pancreatic necrosis (7, 17.5%). A combination of preventive measures allowed the attainment of low rates of esophagojejunal anastomotic leakage (0.8%). CONCLUSION We believe that the decision to perform an urgent reexploration, based on clinical findings, should generally be made by a group of experienced surgeons (not only the primary surgeon). Timely relaparotomy prevented death in 37.5% of the patients with serious acute postoperative complications.

Primary non-Hodgkin's lymphoma of the stomach: Three radical modalities of treatment in 75 patients

AbstractBackground: Non-Hodgkins lymphoma (NHL) remains a rare form of gastric malignancy, with a rising incidence. Approaches to treatment vary from surgery alone to conservative management. Methods: To determine the optimal scheme of treatment, a randomized clinical trial was undertaken. Seventy-five patients were randomized into three groups: A—surgery alone (25), B—surgery followed by chemotherapy (29), and C—radiation therapy followed by surgery and chemotherapy (21). Forty-nine patients had stage IE and 26 had stage IIE disease. Chemotherapy (COP and COPP) consisted of 6 courses during a 1-year period, with the courses being 6 weeks apart. Results: Subtotal gastrectomy was performed in 26 patients. Forty-nine patients underwent total gastrectomy. Postoperative complications occurred in 6 (8%) patients: 3 (12%) in group A, 2 (6.9%) in group B, and 1 (4.7%) in group C. Postoperative mortality occurred in 2 (8%) patients in group A (2.7% of all patients). An increase in hospital admissions number per year and decrease of mean age of patients with NHL of the stomach after the Chernobyl accident on April 26, 1986 was noted. Conclusions: Improved survival in gastric NHL was achieved by a combination of preoperative radiation with surgery and postoperative chemotherapy, presumptively through the management of local and systemic disease.

Apoptosis induced by hyperthermia and verapamil in vitro in a human colon cancer cell line.

The aim of this study was to determine the mechanisms responsible for the growth inhibitory effect of hyperthermia and verapamil in human colon cancer cell line HT-29. Apoptotic cell death was verified by flow cytometry analysis. The effect of treatment with hyperthermia and verapamil on the expression of apoptosis-associated proteins including Bcl-2, p53, bax, and c-Myc was studied by Western blot analysis. Changes in intracellular calcium homeostasis was analysed by fluorescence microscopy. The combination of 42 degrees C hyperthermia and verapamil caused a significant delay of human colon cancer cell proliferation as a result of apoptosis. Administration of these agents alone did not cause any cell inhibitory effect. Our experiments have shown that HT-29 cells constitutively express apoptosis-promoting proteins, such as Bax and c-Myc, while they fail to produce Bcl-2. Therefore, we hypothesize that HT-29 cells must have Bcl-2 independent pathways to protect cells against death-inducing signals. Also, apoptosis of HT-29 cells produced by hyperthermia in the presence of verapamil is a p53-independent process. Verapamil, when it did not act as a calcium channel blocker or inhibitor of release from intracellular storages under hyperthermic conditions, accelerated the increase of [Ca2+]i in HT-29 cells which resulted in programmed cell death (apoptosis).

In vitro Effect of 5-Fluorouracil, Verapamil and Hyperthermia on the Human Pancreatic Adenocarcinoma Cell Line ASPC-1

The purpose of this study was to assess the efficacy of verapamil (20 microM) and hyperthermia (42 degrees C) as modifiers of 5-fluorouracil (5-FU) used at different concentrations, in inhibiting the growth of human pancreatic adenocarcinoma cells. Combined verapamil and hyperthermia treatment significantly decreased cell count by 63.8% when compared to the control. Verapamil drastically enhanced the growth inhibitory effect of 5-FU at all concentrations. At high-concentration 5-FU (50 micrograms/ml), verapamil and hyperthermia had a synergistic growth-inhibitory effect and caused a significant decrease in cell count by 81.4% in comparison to the control. The modalities analyzed in this study require further investigation and have potential for clinical applicability to pancreatic cancer therapy in the future.

Carcinoma of the stomach following the Chernobyl nuclear accident

Medical consequences of many nuclear accidents on humans are well studied, but the results pertaining to gastric cancer patients who were exposed to radiation as a result of the Chernobyl nuclear accident have not been analysed. In this study, the outcome of the surgical treatment of 68 gastric cancer patients who were exposed to radiation as a result of the Chernobyl nuclear accident was compared with that of 117 consecutive gastric cancer patients from uncontaminated areas of the Ukraine. Patients in the study group was significantly younger than that of the control group. Comparative analysis showed the same frequency of regional metastases (65.7% versus 71.1%, P > 0.05), but a smaller number of distant metastases (23.8% versus 38.1%, P < 0.05) in the study group. 41.2% of patients in the study group underwent total gastrectomy compared to 19.6% of patients in the control group (P = 0.002). Postoperative complications developed in 13.2% of patients in the study group, while postoperative mortality in the study group was 7.3% compared to 1.7% in the control group. A significant decrease in CD16 cells was noted in patients from the study group following the operative procedure. Young age, invasive tumours with smaller number of distant metastases, frequent necessity for total gastrectomy and combined operations with adjacent organs, a higher level of postoperative morbidity and mortality and low levels of natural killer cells (CD16+) with a tendency to decrease after surgery are characteristic of patients with carcinoma of the stomach affected by the Chernobyl accident.

Antitumour activity of 5-fluorouracil, verapamil and hyperthermia against human gastric adenocarcinoma cell (AGS) in vitro

The purpose of this study was to assess the efficacy of verapamil (20 microM) and hyperthermia (42 degrees C) as modifiers of 5-fluorouracil (5-FU), used at different concentrations, in inhibiting the growth of gastric adenocarcinoma cells. Combined verapamil and hyperthermia treatment showed a significant decrease in cell count when compared to control (72.2%), hyperthermia alone (68.4%), or verapamil alone (65%). At a high concentration of 5-FU (50 micrograms/ml), verapamil and hyperthermia had an additive growth inhibitory effect over a 4-day period when compared to control. A combination of 5-FU at low concentration (0.5 microgram/ml) with verapamil significantly suppressed growth by 31.2% in comparison to control--with this effect being independent of the duration of treatment. The modalities analysed in this study require further investigation and have potential for clinical applicability to gastric cancer therapy in the future.

Pre-operative superselective intra-arterial chemotherapy for the treatment of unresectable gastric carcinoma

From February 1988 to April 1994, 75 consecutive patients with unresectable gastric carcinoma were included in this prospective randomized study. Patients were randomized as follows: 26 patients received exploration or palliative surgery alone (S), 24 received pre-operative systemic intravenous chemotherapy and surgery (IVCH+S) and 25 received pre-operative superselective intra-arterial chemotherapy and surgery (IACH+S). In patients whose tumors were located on the lesser curvature, the left gastric artery was catheterized. In all other cases, the right gastroepiploic artery was catheterized. 5-Fluorouracil (5-FU) and doxorubicin (DR) were selected as the chemotherapeutic agents for both IVCH and IACH. Dosages were determined using a actual body surface area (BSA) calculation and a standard height and weight nomogram. The drug infusion was administered in two cycles with a 6 day interval approximately two weeks prior to surgery. The intravenous regimen was given at the same dosage and timing as the intra-arterial regimen. The median survival time after S and IVCH+S was only 91 and 96 days, respectively, as compared to 401 days in patients receiving IACH+S. The results confirmed that IACT + S conferred a highly significant survival advantage compared to S or to IVCH+S, adjusted for all patient characteristics (p > 0.0001).