Itsuo Miyazaki

Prognostic factors of hepatocellular carcinoma in patients undergoing hepatic resection

BACKGROUND/AIMS Prognostic analysis on hepatocellular carcinoma (HCC) in patients undergoing hepatectomy is necessary to determine the clinical value of hepatectomy on prognosis. METHODS Survival and disease-free survival were analyzed in 104 HCC patients undergoing hepatectomy using clinicopathologic factors by univariate and multivariate analyses. The value of the International Union Against Cancer (UICC) TNM classification on prognosis was assessed in the patients. RESULTS In multivariate analysis, portal vein invasion was the most influential factor. The difference between stage 1 and 2 or stage 3 and 4A using UICCs TNM classification was not significant with respect to survival or disease-free survival. The UICCs classification was modified as follows; stage 1, solitary tumor without vascular invasion; stage 2, solitary or multiple tumor(s) involving adjacent to vessel branch; stage 3, tumor(s) involving major vessel branch or with regional lymph nodal metastasis; and stage 4, tumor(s) with distant metastasis. The differences between each stage in the modified classification were significant with respect to disease-free survival. CONCLUSIONS The UICCs TNM classification was not of prognostic significance. Further studies on survival in patients with HCC are necessary to evaluate the value of the UICCs TNM classification; some modification may be necessary.

An evaluation of radical resection for pancreatic cancer based on the mode of recurrence as determined by autopsy and diagnostic imaging.

Background. To determine the extent of dissection in curative resection for cancer of the pancreatic head, the mode of recurrence was determined at autopsy and by radiographic examinations.

Reflux of duodenal or gastro‐duodenal contents induces esophageal carcinoma in rats

Esophageal adenocarcinoma arises from Barretts esophagus, which is induced by gastro‐esophageal reflux. This refluxate often contains duodenal contents, whose backflow triggers gastric carcinoma, suggesting the hypothesis that refluxed duodenal contents cause esophageal carcinoma. This study examines the role of duodenal and gastric reflux in the absence of exogenous carcinogens in esophageal carcinogenesis. Wistar male rats, 120 in all, each weighing approximately 250 g, were used. Three experimental procedures were performed to produce gastro‐duodeno‐esophageal reflux, duodeno‐esophageal reflux and gastro‐esophageal reflux, for comparison with 2 control procedures, Roux‐en‐Y reconstruction and a sham operation. The animals were fed a standard diet and were examined 50 weeks after surgery. While no carcinoma was found among the 16 gastro‐esophageal‐reflux, 11 Roux‐en‐Y and 12 sham‐operation animals, 10 of the 12 animals with gastro‐duodeno‐esophageal reflux (83%) and 10 of the 13 with duodeno‐esophageal reflux (77%) developed esophageal carcinoma. The difference between groups was significant (p < 0.001). Two animals with gastro‐duodeno‐esophageal reflux had esophageal double and triple carcinomas respectively. Of the 23 carcinomas, 16 were adenocarcinoma, 4 adenosquamous carcinoma, and 3 squamous‐cell carcinoma. Adenocarcinoma developed from the columnar‐lined epithelium near the esophago‐jejunostoma, while adenosquamous and squamous‐cell carcinoma arose from the squamous esophagitis. These observations demonstrate that refluxed duodenal contents per se are responsible for esophageal carcinogenesis.

Effects of intraoperative chemohyperthermia in patients with gastric cancer with peritoneal dissemination

BACKGROUND The most common cause of noncurative resection and recurrence is gastric cancer is peritoneal seeding. However, the results of treatment of peritoneal dissemination with chemotherapy have been poor with 5-year survival rates of 0%. METHODS A new in vitro thermochemosensitivity test was performed on gastric cancer cells obtained from 19 surgically resected specimens by using tetrazolium-based colorimetric assay (MTT assay). A novel treatment of the intraoperative chemohyperthermia was undertaken in 83 patients with gastric cancer with peritoneal dissemination. After aggressive resection of primary tumor, lymph nodes, and peritoneal metastases, warmed saline solution containing mitomycin C 30 mg, etoposide 150 mg, and cisplatin 300 mg was introduced into the peritoneal cavity via a closed circuit continuous hyperthermic peritoneal perfusion (CHPP) for 60 minutes to keep the abdominal temperature at 42 degree to 43 degrees C by means of a heat exchange mechanism. RESULTS The in vitro thermochemosensitivity test that 43 degrees C enhanced the cytotoxin effects on gastric cancer cells under clinically achievable drug concentrations. During CHPP, drug concentrations of cisplatin, mitomycin C, and etoposide in the perfusate remained statistically higher than in the peripheral venous circulation. Among 43 evaluable patients with residual peritoneal seeding, eight (19%) and nine (21%) exhibited complete response and partial response, respectively. The overall 1- and 5-year survival rates were 43% and 11%, respectively. Patients who underwent complete resection survived significantly longer than those with residual disease, and those with complete response had a significantly better prognosis than did those with partial response, and nonresponders. One-year survival rates with complete response, partial response or nonresponders were 88%, 27% and 22%, respectively. Five patients survived longer than 5 years. CONCLUSIONS Our triple treatment combining surgery and CHPP is an effective therapy for selected patients with gastric cancer with peritoneal dissemination.

Results of extensive surgery for pancreatic carcinoma

Since 1973, 210 patients with pancreatic carcinoma have undergone surgery in our clinic, including 144 with carcinoma of the head of the pancreas. Of these 144 patients, macroscopic curative resections were performed on 53 (36.8%). Five patients (9.4%) died within 30 postoperative days, and an additional 3 (5.7%) died within 60 days. The overall median survival was 13 months. Eight of the patients who underwent macroscopic curative resection survived 5 years, giving a 5‐year survival rate of 27.4% using the Kaplan–Meier method. The 5‐year survival rate was 39.7% after a microscopically curative resection and 0% after a microscopically noncurative resection.

Amelioration of diabetes mellitus in partially depancreatized rats by poly(ADP-ribose) synthetase inhibitors. Evidence of islet B-cell regeneration.

Ninety percent depancreatized rats received daily intra-peritoneal injection of 0.5 g/kg nicotinamide and 0.05 g/kg 3-aminobenzamide, potent inhibitors of islet poly(ADP-ribose) synthetase. One to three months after the partial pancreatectomy, urinary and plasma glucose levels in nicotinamide- and 3-aminobenza-mide-treated rats were markedly lower than those in saline-treated control rats. Morphologic examination of the remaining pancreata revealed that islets in the poly(ADP-ribose) synthetase inhibitor-treated rats were markedly enlarged and consisted largely of B-cells. These results suggest that poly(ADP-ribose) synthetase inhibitors induce islet B-cell regeneration, thereby preventing or improving diabetes mellitus in partially depancreatized rats.

Expression of p53 protein in colorectal cancer and its relationship to short‐term prognosis

Background and Methods. The expression of p53 protein in 100 large bowel cancers was studied immuno‐histochemically by use of a monoclonal antibody (PAb1801).

Surgical strategy for carcinoma of the pancreas head area based on clinicopathologic analysis of nodal involvement and plexus invasion.

BACKGROUND The pattern of tumor spread, vis-à-vis nodal involvement and invasion of the extrapancreatic plexus (Plx), has not been thoroughly described for carcinoma of the pancreatic head area. METHODS From 1973 to 1991, 110 patients (49 with carcinoma of the pancreatic head [Ph], 29 with distal bile duct cancer [Bi], and 32 with carcinoma of the papilla of Vater [Pv]) underwent pancreatectomy at Kanazawa University Hospital. Nodal involvement and Plx invasion were precisely evaluated by histopathologic examination. RESULTS Thirty-seven (76%) of the 49 patients with Ph, 20 (69%) of the 29 with Bi, and 14 (44%) of the 32 with Pv had nodal involvement. The lymph nodes most commonly involved for Ph were the posterior pancreaticoduodenal lymph nodes (numbers 13a [superior] and 13b [inferior]), the superior mesenteric lymph nodes (number 14), the paraaortic lymph nodes (number 16), and the anterior pancreaticoduodenal lymph nodes (number 17) (13a, 51%; 13b, 47%; 14, 36.7%; 16, 18.4%; 17a, 33%; 17b, 22%). In patients with Bi, lymph nodes around the hepatoduodenal ligament (number 12) and lymph nodes numbers 13a and 14 were most commonly involved (12, 27.6%; 13a, 51.7%; 14, 34.5%). In patients with Pv, lymph node numbers 13b and 14 were most frequently involved (13b, 34.4%; 14, 15.6%). No significant correlation was noted between the tumor size and nodal involvement in these three lesions. Nodal involvement was an important prognostic factor for carcinoma of the pancreatic head area. Plx invasion in these three carcinomas was observed in 61% of patients with Ph, 29% of patients with Bi, and 3% of patients with Pv. CONCLUSIONS Nodal involvement and Plx invasion differed significantly among carcinomas of the pancreatic head area. We believe that nodal dissection of at least group number 14 is needed for Ph, Bi, and Pv cancers. In addition, dissection of lymph nodes of number 16 and the Plx around the superior mesenteric artery and celiac axis are needed in Ph cancer. Plx dissection of the first portion of plexus pancreaticus capitalis is needed in Bi cancer.

Clinical study of lymphatic flow to the paraaortic lymph nodes in carcinoma of the head of the pancreas

Background. At Kanazawa University, the authors have been developing an appropriate radical operation for the treatment of cancer of the head of the pancreas. As a result of previous research, it was believed that lymphatic metastasis of carcinoma of the head of the pancreas should be investigated more thoroughly to improve the surgical results.

Chemoprevention of DMBA-induced mammary carcinogenesis in rats by low-dose EPA and DHA

We investigated the effects of low-dose eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the incidence and growth of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma in rats fed a high-fat (HF) diet. We also examined the effects of these treatments on the fatty acid composition of tumour and serum. Tumour incidence was significantly decreased by the administration of low-dose EPA and DHA, whereas their inhibitory effects on tumour growth did not reach significance. Serum arachidonic acid (AA) level was decreased by the administration of low-dose EPA and tended to be decreased by the administration of low-dose DHA, whereas tumour AA levels were not changed. The administration of low-dose EPA and DHA may be useful for inhibiting the incidence of breast cancer.