Kimio Namatame

Efficacy of intraportal injection of anti-ICAM-1 monoclonal antibody against liver cell injury following warm ischemia in the rat.

BACKGROUND Increased expression of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte-function-associated antigen-1 (LFA-1) has been reported to play a major role in reperfusion injury after ischemia. In the present study we tested the effects of anti-rat-ICAM-1 monoclonal antibody (1A29) on partial-liver warm ischemia in rats. METHODS Histological changes and expression of ICAM-1 and LFA-1 were investigated in rat partial-liver warm ischemia, performed by clamping hepatic hilar vessels distributing to the right lateral lobe for 30, 45, and 60 minutes. In a second study, the effects of intraportal 1A29 injection after 60 minutes of warm ischemia in the rat were examined histologically. In both studies, the liver tissue was removed for analysis 48 hours after clamping. RESULTS Reperfusion after 60 minutes of warm ischemia induced histological liver injury and strong expression of ICAM-1 and LFA-1, although 30 and 45 minutes of ischemia did not provoke either histological damages or the expression of ICAM-1 and LFA-1. Intraportal injection of 1A29 after 60 minutes of warm ischemia clearly suppressed liver cell injury histologically. CONCLUSION Intraportal injection of 1A29 prevented the histological inflammation of an ischemic liver and may be useful in liver surgery or liver transplantation, because high concentrations can reach the target organ and nonspecific immunosuppression in other tissues and organs can be decreased.

Endoscopic Hemostasis in Hemorrhagic Gastric Ulcer—Effectiveness of the Hemoclipping, Ethanol Injections and Heat Probe—

Abstract: The hemostatic effects of hemoclipping, the pure ethanol local injection method and the heat probe methods on hemorrhagic gastric ulcers associated with exposed blood vessels, were compared. The locations of the ulcers and exposed blood vessles, as well as characteristics and the severity of the hemorrhage were discussed. The hemoclipping method was used on 59 patients, the pure ethanol local injection on 32 patients, and the heat probe methods on 26 patients. The hemoclipping and pure ethanol local injection methods were effective in all of the patients in whom the exposed blood vessels were present around the margin of ulcers. The efficacy rate was 91%, 92% and 92%, respectively, when exposed blood vessels were found at the base of the ulcer. The efficacy rate was 94%, 100% and 80% for the three hemostatic methods, respectively, when an oozing hemorrhage was present. The three methods had an efficacy rate of 100% when only blood clots were present. The efficacy rate for a spurting hemorrhage was 86%, 71% and 67%, respectively, for the three methods. The hemoclipping and pure ethanol local injection were effective in 100% of slight and moderate hemorrhage cases, while the heat probe method was effective in only 89% of moderate cases. The efficacy rate was 85%, 85% and 83%, respectively, for severe cases. Overall, the efficacy rate was 93% for the hemoclipping method, 94% for the pure ethanol local injection and 92% for the heat probe method, and there was no significant difference between the three methods with regard to the overall efficacy rate.

Histopathological response to preoperative chemotherapy including 5-fluorouracil additionally assessed by immunocytochemical and pharmacologic parameters in patients with advanced gastric cancer.

To investigate quantitative methods for assessing the response to preoperative downstaging chemotherapy (PDC), the immunocytochemical expression of proliferating cell nuclear antigen (PCNA) and bromodexoyuridine (BrdU) as well as a pharmacologic study of the rate of thymidylate synthetase inhibition (TSIR) were studied in resected specimens obtained from patients with advanced gastric cancer. Fifty-one patients with advanced gastric cancer who received PDC (30 with 5-fluorouracil peroral administration and the other 21 with intravenous administration of 5-fluorouracil and cisplatin) were studied. The labeling index of PCNA (PCNA-LI) and BrdU were measured. The PCNA suppression (PCNA-S), which was measured by both the values of prechemotherapeutic PCNA-LI in endoscopically biopsied specimens and postchemotherapeutic PCNA-LI in resected specimens, was also examined. TSIR was measured by a protein-bound radiochemical method. We compared the above-mentioned parameters with the histopathological response to PDC according to the General Rules for Gastric Cancer Study. In the patients with peroral 5-flurorouracil, a stepwise regression analysis showed that TSIR is a significantly effective for determining the histopathological response to PDC. In the patients with 5-fluorouracil and cisplatin, PCNA-S was the most effective indicator of the histopathological response to PDC, as shown by a stepwise regression analysis. The present study thus showed that both TSIR and PCNA-S were effective additional indicators of the histopathological response to PDC.

Prognostic evaluation of curatively resected locally advanced gastric cancer patients with preoperative downstaging chemotherapy assessed by histochemical and pharmacologic means.

The aim of the present study was to investigate whether the rate of thymidylate synthetase inhibition (TSIR) and the rate of proliferating cell nuclear antigen expression (PCNA-R) in gastric cancer tissues, which can be obtained within a short period after surgery, were predictive and quantitative prognostic factors for locally advanced gastric cancer patients with preoperative down-staging chemotherapy. Curatively resected 30 locally advanced gastric cancer patients with preoperative chemotherapies were studied. Three-year survival analysis showed that the higher TSIR and the lower PCNA-R significantly predicted better prognosis (p < 0.01 and p < 0.05, respectively). Multiple regression test showed that the TSIR was a significantly predictive variable for 1-year survival (p < 0.05). The TSIR and PCNA-R could be predictive and quantitative prognostic factors in advanced gastric cancer patients who received preoperative downstaging chemotherapy.

Abstracts of Selected Papers Presented at the 31st Annual Meeting of the Japanese Society of Gastroenterology

S OF SELECTED PAPERS PRESENTED AT THE 31ST ANNUAL MEETING OF THE JAPANESE SOCIETY OF GASTROENTEROLOGY October 5-7, 1989, Asahikawa, Japan Chairman: Masayoshi NAMIKI, M.D.

Endoscopic Therapy of Early Gastric Cancer —Comparison of Endoscopic Mucosal Coagulation and Resection—

Abstract: The clinical efficacy of various methods of endoscopic treatment was evaluated in 70 patients with early gastric cancer. The treatments included using an Nd‐ YAG laser on 22 patients (2 IIa cases, 3 IIa + IIc cases and 17 IIc cases), a heater probe on 2 patients (IIc) and endoscopic mucosal resection (EMR) on 46 patients (13 I cases, 15 IIa cases, 2 IIa + IIc cases and 16 IIc cases). Laser irradiation and the heater probe method (endscopic mucosal coagulation; EMC), which cause coagulation and necrosis to lesions using heat energy, were found to be successful for well differentiated adenocarcinoma confined to the mucosa even if the size of the lesions was 20 mm and over. Poorly differentiated adenocarcinoma with lesions 20 mm or smaller reoccurred, and only well differentiated adenocarcinoma with infiltration limited to the mucosa seemed to be treatable endoscopically by EMR. Whether or not total resection was possible was determined with respect to the size and site of lesions in patients treated by EMR. Great therapeutic efficacy was achieved when the lesions were 10 mm or smaller and located in the anterior wall or the greater curvature. Piecemeal resection had to be made in a majority of cases when the lesions measured 10 mm or more or were located in the lesser curvature or the posterior wall. Therefore, endoscopic EMR is recommended if the size of the lesions is 10 mm or less, while EMC must also be considered if the lesions are larger or piecemeal resection is required.