Oichiro Kobori

Early gastric caner

In order to decide on a treatment strategy against gastric cancers, an accurate preoperative evaluation of the depth of cancer invasion is essential. Preoperative endoscopic diagnosis of the depth of invasion was compared with pathological results of the resected specimen in 206 early gastric cancers and 32 early-like advanced gastric cancers. The endoscopic distinction between early and early-like advanced cancers was correctly made in 83.6% of the cases. Among the early gastric cancers, mucosal and submucosal invasion was correctly presumed in 71.9% of the cases. When the tumor was an elevated type, or located in the antrum, the endoscopic diagnosis tended to be deeper than the true depth. The size of tumor contributed little to the depth diagnosis. Pathomorphological changes on the tips of converging folds were the important clue for diagnosing depth.In order to decide on a treatment strategy against gastric cancers, an accurate preoperative evaluation of the depth of cancer invasion is essential. Preoperative endoscopic diagnosis of the depth of invasion was compared with pathological results of the resected specimen in 206 early gastric cancers and 32 early-like advanced gastric cancers. The endoscopic distinction between early and early-like advanced cancers was correctly made in 83.6% of the cases. Among the early gastric cancers, mucosal and submucosal invasion was correctly presumed in 71.9% of the cases. When the tumor was an elevated type, or located in the antrum, the endoscopic diagnosis tended to be deeper than the true depth. The size of tumor contributed little to the depth diagnosis. Pathomorphological changes on the tips of converging folds were the important clue for diagnosing depth.

Effect of Age on the Relationship between Gastric Cancer and Helicobacter pylori

Helicobacter pylori is thought to be involved in the pathogenesis of gastric cancer, but the time point at which it produces its effects (critical time) is unknown. We measured the serum level of H. pylori antibody in 787 gastric cancer patients and 1007 controls aged 20 to 69. Odds ratios for different gastric cancer types and stages were determined for each 10‐year age class. The overall odds ratio for gastric cancer decreased with age, being 7.0 for those aged 20–29, 14.5 for those aged 30–39, 9.1 for those aged 40–49, 3.5 for those aged 50–59, and 1.5 for those aged 60–69 (trend in odds ratios: P < 0.01). However, there was no such age‐dependent trend for early diffuse‐type cancer; the odds ratios were 12.6, 4.0, 7.2, 6.5, and 18.5 respectively (P=0.29). Early cancer tended to show higher seroprevalence than advanced cancer, especially in older subjects. No significant difference in seroprevalence was observed between diffuse and intestinal cancers within each age‐class. Seroreversion must have occurred in the time interval between the critical time and the diagnosis of the cancer, especially in older patients. The age‐dependent relationship between H. pylori and gastric cancer may be due to seroreversion, which itself may be independent of age. This age‐independence indicates that prolonged exposure to H. pylori does not increase the magnitude of its influence on gastric carcinogenesis. Possible mechanisms through which H. pylori exerts pathogenic effects are continuous inflammation in adulthood and/or irreversible damage to gastric mucosa in childhood or the teenage years.

U-shaped effect of drinking and linear effect of smoking on risk for stomach cancer in Japan.

A case‐control study was conducted to evaluate the relationship between smoking or drinking doses and risk for stomach cancer, and to clarify whether the relationship is dose‐dependent or U‐shaped. Smoking dose was categorized as 0,1–399, 400–799, or 800+ cigarette‐years, and drinking dose as 0, occasional/0.1–134.9, 135–1349.9, or 1350+ alcohol‐years (ml of pure alcohol intake per day multiplied by years of drinking). Helicobacter pylori status was determined by serology for adjustment. Using logistic regression, the adjusted effects of smoking and drinking doses on risk for stomach cancer were calculated for both genders. Among male subjects, the odds ratios (95% confidence intervals (CIs)) were 1.29 (0.76, 2.18) for 1–399, 1.71 (1.05, 2.80) for 400–799 and 2.46 (1.49, 4.07) for 800+ cigarette‐years compared with never‐smokers, and 1.89 (0.97, 3.69) for never‐drinkers, 2.82 (1.63, 4.86) for 135–1349.9 and 2.84 (1.97, 4.83) for 1350.0+, compared with occasional/0.1–134.9 alcohol‐years. Among female subjects, they were 0.44 (0.20, 1.00) for 1–399 and 2.471 (0.91, 6.68) for 400+ cigarette‐years compared with never‐smokers, and 1.54 (0.90, 2.63) for never‐drinkers and 1.39 (0.66, 2.93) for 135.0+ alcohol‐years. Smoking seems to exert a linear effect and drinking, a J‐ or U‐shaped effect on risk for stomach cancer, although there might be a dip of risk in light smokers among female subjects.

Effect of oral administration of protease inhibitor on pancreatic exocrine function in WBN/Kob rats with chronic pancreatitis.

The effect of oral administration of protease inhibitor (camostat) on pancreatic morphology and exocrine function (conscious rat model) was investigated using WBN/Kob rats with spontaneous chronic pancreatitis. In nontreated WBN/Kob rats (2–12 months of age), pancreatic fibrosis and parenchymal destruction compatible with human chronic pancreatitis appeared at 3 months and advanced with each month. Pancreatic secretion was markedly impaired at all ages. In WBN/Kob rats fed diets containing camostat (from 2–3 or 4–5 months of age), the pancreas was hypertrophic and did not show any histological appearances compatible with chronic pancreatitis, and moreover, exocrine function was thoroughly restored with increased plasma cholecystokinin concentrations. Oral administration of protease inhibitor has both preventive and therapeutic effects on pancreatic lesions and dysfunction in an animal model of chronic pancreatitis, probably via endogenous cholecystokinin release.

Vitamin D status after total gastrectomy

Serum levels of 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, 1,25-dihydroxyvitamin D, immunoreactive parathyroid hormone, and urinary excretion of nephrogenous cyclic AMP were measured in 25 patients after total gastrectomy. Two types of reconstruction after total gastrectomy were also compared. Serum 25-hydroxyvitamin D levels were significantly decreased and serum 24,25-dihydroxyvitamin D levels were markedly reduced, whereas serum 1,25-dihydroxyvitamin D levels were significantly increased in the patients. Although serum levels of immunoreactive parathyroid hormone did not show a significant difference, serum alkaline phosphatase levels and urinary excretion of nephrogenous cyclic AMP were significantly increased in the patients. The results suggest that defective vitamin D storage and enhanced vitamin D action coexist in patients after total gastrectomy and that the enhanced vitamin D action, possibly derived from slightly increased parathyroid function, would be a compensatory mechanism to sustained calcium deficiency. No substantial difference of vitamin D status was observed between the two types of reconstruction which differed in passage through the duodenum.

The macroscopic diagnosis of lymph node metastasis from early gastric cancer.

As the proportion of early gastric cancers (EGC) has been steadily increasing, modifications of the “radical lymphadenectomy” approach to stomach cancer have been attracting considerable attention; however, accurate pre- and intraoperative evaluations of tumor extent are essential for the successful application of this method. We examined the reliability of macroscopically diagnosing node involvement by reviewing the operative and pathological records of 522 patients with EGC. Of 59 patients histologically diagnosed as node-positive (n+), only 19 (32%) had been macroscopically diagnosed as node-positive (N+). In contrast, of 61 N+ patients, 42 (69 %) were in fact n-. Metastases from histologically diffuse type carcinomas were less accurately diagnosed than those from intestinal type tumors. In 44% of the false-positive (N+/n-) patients, the tumor had been preoperatively diagnosed as advanced, which seemed to have lead to intraoperative overdiagnosis. These results suggest that lymph node metastases from EGC cannot be reliably diagnosed during surgery. The indications for a modified radical operation should thus be decided according to preoperative tumor evaluation based on the depth of invasion.

Immunotherapy for Stewart-Treves syndrome: Usefulness of intrapleural administration of tumor-infiltrating lymphocytes against massive pleural effusion caused by metastatic angiosarcoma

We describe a 56-year-old woman with Stewart-Treves syndrome who had severe dyspnea from a pleural effusion caused by metastatic angiosarcoma in the right lung. Tumor-infiltrating lymphocytes (TIL) in the pleural effusion were cultured and expanded in vitro in the continuous presence of recombinant interleukin 2 with periodic stimulation by CD3 antibody. The expanded TIL were administered intrapleurally seven times at 1- to 4-week intervals in combination with intravenous infusion of recombinant interleukin 2. A panel of T-cell clones was also obtained from TIL. Immunotherapy dramatically improved the patients dyspnea and pleural effusion. A CD4+ T-cell clone and a CD8+ T-cell clone established from TIL had specific cytotoxicity to the tumor cells.

A new in vivo staining method, cresyl violet staining, for fiberoptic magnified observation of carcinoma of the gastric mucosa

SummaryA polypoid gastric mucosal lesion with a flat portion was observed by a fiberoptic magnifying endoscope with a new in vivo staining method, cresyl violet staining. The fine surface structure of this lesion showed a characteristic “ruined sulciform pattern” suggesting papillary carcinoma histologically. Successful application of the findings of dissecting microscopy to clinical magnifying endoscopy by means of this new staining material indicates the possibility of diagnosing gastric mucosal carcinomas with much more accuracy.

Superficial carcinoma of the esophagus

SummaryNine cases of superficial carcinoma of the esophagus were described. Although 3 patients complained of abnormal sensation on swallowing or dysphasia, 6 patients did not present with any symptoms related to the esophageal lesion. The radiologic diagnosis is particularly difficult in cases with superficial type esophageal cancer, and no definitive findings were obtained in three such cases. However, esophagoscopy using Lugol spray was far more effective for the recognition of these superficial lesions. Although surgical resection of the esophagus is technically easier in these cases, the indications of surgery should be carefully evaluated. One operative death occurred in our series. In cases that are good indications, however, wide lymph node dissection should be carried out, since metastases occur even to distant lymph nodes, particularly in cases with cancer invasion of the submucosal layer. The histopathologic diagnosis was squamous cell carcinoma in 8 cases, but in one case it was adenocarcinoma of mucus-secreting gland origin in the mid-thoracic esophagus.

Marked and prolonged depression of Factor XIII after esophageal resection

Anastomotic leakage is one of the most common complications of esophagectomy and, since Factor XIII is required for normal wound healing, we investigated the temporal changes in plasma Factor XIII following esophagectomy and hepatectomy. A control group of patients undergoing other abdominal operations was also studied. Factor XIII activity was determined before surgery and on postoperative days (POD) 1, 3, 7 and 14. The plasma levels of acute phase protein were also measured. The plasma Factor XIII activity decreased significantly in both the hepatectomy and control groups until POD 7, reaching the lowest level on POD 3. In contrast, the esophagectomy group showed significant decreases in Factor XIII levels throughout the postoperative study period, with a nadir with an average activity of 56 per cent on POD 7. Preoperative transferrin levels had a positive correlation with Factor XIII levels measured on POD 3 and there was also a positive significant correlation between Factor XIII activity and alpha 2-macroglobulin levels on POD 3. These results suggest that there is a marked and prolonged depression of plasma Factor XIII activity following esophagectomy which may be attributed to accelerated tissue demands, inadequate synthesis or increased degradation. Moreover, the severe and sustained decrease in Factor XIII activity may be related to poor wound healing after esophagectomy.