Akira Nakase

Cumulative Results in 57 Institutions in Japan

In this study the experiences with carcinomas of the pancreas, ampulla of Vater, terminal comma bile duct, and duodenum found in a series of 3,610 patients collected from 57 major Japanese institutions was compiled over a 26 year period. The results were analyzed as to the success of resectional and palliative surgery for the various lesions. The most common lesion was carcinoma of the head of the pancreas. Unifortunately, only 18.3% of these patients were resectable with a 25.3% mortality. Carcinoma of the body and the tail was the second most frequent lesion, and it also exhibited a low resection rate. Carcinomas of the ampulla and the terminal common bile duct and duodenal regions were the most favorable for resection; usually pancreatoduodenectomy with an overall mortality of 20.8%. As a result of the large number of pancreatectomies performed, there was also a large number of postoperative complications, the most frequent being leakage at an anastomotic line. Hemorrhage also occurred frequently. Distal pancreatectomies were reserved for carcinoma of the body and the tail of the pancreas, and the most common postoperative complication of this procedure was hemorrhage. There were only 45 total pancreatectomies among the 973 resections being performed most frequently in patients with carcinoma of the head of the pancreas. Again, the most frequent postoperative complication was hemorrhage, followed by anastomotic leakage. The long term survivals following resection for these lesions were each poor. The best mean survival time was 22.7 months for carcinoma of the ampulla of Vater. Patients having resections for carcinoma of the head of the pancreas had a mean survival time of 12.3 months. At 5 years there were few survivors and most of them were patients who had undergone resections for carcinoma of the ampulla of Vater.

Congenital cystic dilatation of the common bile duct as a cause of primary bile duct stone

Of the 101 patients with congenital cystic dilatation of the common bile duct, eighty-eight with adult-type cysts are reported on. The association of primary bile duct stone and adult-type cyst of this anomaly is discussed and found to be higher than previously recognized. In the cases without calculi, abnormal arrangement of the pancreaticobiliary ductal system is indicated to play an important role in the manifestation of the symptom. The anatomic and clinical features and the results of treatment for this type of cyst are reviewed.

Response of alpha-fetoprotein to chemotherapy in patients with hepatomas

Alpha‐fetoprotein (AFP) was assessed in the sera of 63 patients with hepatomas at the Kyoto University Medical Center. Of 39 patients subjected to chemotherapy, 26 were AFP positive by agar gel precipitation test. Serum AFP in 9 of the patients decreased by more than 50% after the chemotherapy; the decrease continued for longer than 3 months (Group I). Six of the 9 patients had good clinical response, and 3 were evaluated as fair response. AFP in 9 other patients showed a transient decrease of less than 50% and gradually returned to the pretreatment level or slightly above it until death of the patient (Group II). Eight of the 9 had fair clinical response; 1 showed progressive increase in the size of the tumor. All of the remaining 8 patients had continuous increase of serum AFP (Group III) and did not respond to the chemotherapy at all. The pattern of AFP changes classified as Group I to III shows good correlation with clinical response.

Mitochondrial phosphorylative activity and DNA synthesis in regenerating liver of diabetic rats

Abstract The changes in the incorporation rate of [ 14 C]thymidine into hepatic cell DNA and the mitochondrial phosphorylative activity and hepatic energy charge following partial hepatectomy were studied in four groups of diabetic rats (Groups A, B, C, and D), in which diabetes was induced by intravenous injection of alloxan of 35, 49, 63, and 70 mg/kg of body wt. In normal rats, the mitochondrial phosphorylative activity was enhanced maximally during a transient decrease in the hepatic energy charge (ATP+1/2ADP/ATP+ADP+AMP) at 3 hr after partial hepatectomy. The incorporation rate of [ 14 C]thymidine into hepatic cell DNA began about 18 hr later, and reached its peak between the 22nd and 24th hour. In diabetic rats, the enhancement of mitochondrial phosphorylative activity decreased in proportion to the severity of the decrease in the portal-fasting IRI level. The suppression by diabetes in the incorporation rate of [ 14 C]thymidine into hepatic cell DNA was correlated positively with a decrease in the preceding enhancements in mitochondrial phosphorylative activity. In Groups A and B, the energy charge levels decreased but were restored rapidly, while those of Groups C and D decreased linearly without restoration. It is suggested that since biosynthetic enzymatic activities exhibit high activity at an energy charge above 0.85, the depression of DNA synthesis in the regenerating liver of diabetic rats is due, at least partially, to a decrease in the hepatic energy charge, which is based on suppression of an enhancement in mitochondrial phosphorylative activity following insulin deficiency.

Evaluation of hepatoma chemotherapy by α-fetoprotein determination

Abstract Effects of chemotherapy on twenty-nine histologically proved and α-fetoprotein (AFP)-positive hepatomas were evaluated by changes in serum AFP levels according to the criteria of our previous report. By transfemoral local infusion of mitomycin C, six of eight patients showed more than 50 per cent decrease of AFP levels and regression of the tumor, and the others showed fair effects. By single shot infusion, 50 per cent decrease of serum AFP levels and tumor regression were noted only in three of thirteen patients, and chemotherapy by systemic infusion in eight patients was much less effective. As evaluated by AFP levels, histologically well or moderately differentiated hepatocellular carcinomas responded better to chemotherapy than poorly differentiated ones.

Studies of the growth and infiltration of experimental tumor of the pancreas in rabbits

An experimentally transplanted pancreatic cancer was induced by means of an intraductal injection of Vx2 carcinoma supernatant into the pancreatic duct of rabbits. The presence of ductal obstruction appeared to assist the nidation and growth of injected cancer cells in the pancreas. Tumors induced in the head of the pancreas grew by extension to the body and tail where they also produced interspersed, nodular tumor masses. Tumors induced in the body and tail region, on the other hand, grew by direct expansion towards the head, but this did not produce the interspersed nodular tumors in the head portion. These observations indicate that cancer of the head of the pancreas associated with the stenosis or obstruction of the pancreatic duct resulted in ductal dissemination and extensive lymphatic infiltration in the body and tail, a wider cancer invasion than recognizable at the gross cancer border. This extension was noncontinuous and interspersed, so that radical curative surgery for such cancer of the head of the pancreas would indicate total pancreatectomy.

Heterotopic autotransplantation of a pancreas segment with enteric drainage after total or subtotal pancreatectomy for chronic pancreatitis

SummaryFour patients with chronic alcoholic pancreatitis and one patient with idiopathic chronic pancreatitis, who had total or subtotal distal pancreatectomies for persistent pain, underwent simultaneous autotransplantation of a pancreas segment to preserve the pancreatic function. The segment was autotransplanted heterotopically to the iliac fossa with anastomosis of the splenic vessels to the iliac vessels to prevent reinnervation, and the pancreatic duct was anastomosed to the intestine to preserve exocrine function. Postoperatively, the patency of the graft vessels was confirmed by angiography in every patients. Complete pain relief has been obtained in all patients with a followup duration of 4–89 mo. Except for one patient who had been treated preoperatively with insulin injections for diabetes, the patients remained normoglycemic without exogenous insulin administration and demonstrated satisfactory insulin secretion during a 75-g oral glucose tolerance test. An exocrine pancreatic diagnostant test usingp-aminobenzoic acid yielded nearly similar levels to the preoperative value for all patients. Heterotopic autotransplantation of the pancreas segment appears to be effective for preserving pancreatic function, as well as providing permanent pain relief for patients with chronic pancreatitis who require extensive resection of the pancreas.

Heterotopic autotransplantation of the distal pancreas segment after total pancreatectomy for cancer of the head of the pancreas.

Autotransplantation of the distal pancreas segment with pancreaticojejunostomy was performed in four patients with cancer of the head of the pancreas to preserve endocrine pancreatic function after extended total pancreatectomy. All patients had tumor involvement of both the celiac axis and the portal vein. The pancreatic graft was determined to be cancer-free by frozen section histologic and pancreatic juice cytologic examinations. The distal pancreas segment was autotransplanted to the iliac vessels heterotopically and placed in the extraperitoneal pocket to avoid untoward effects of any local recurrence or pancreatic leakage. This procedure, in the form of reconstruction, might be called modified subtotal pancreatoduodenectomy. Postoperatively, all patients remained normoglycemic without exogenous insulin administration, and their quality of life was considered satisfactory.

Current status of benign biliary disorders in Japan and accuracy rates of preoperative diagnoses: Collective review of 14,654 patients

Data on 14,654 patients preoperatively diagnosed for benign lesions who had undergone surgical treatment during a 2 year period (April 1979 to March 1981) were obtained from 145 institutions. A total of 18,891 biliary disorders were confirmed and classified into 18 groups: stones in the gallbladder, 12,272 patients (83.7 percent of all patients); stones in the extrahepatic bile duct, 3,605 patients (24.6 percent); stones in the intrahepatic bile duct, 570 patients (3.9 percent); acalculous cholecystitis, 463 patients (3.2 percent); idiopathic dilatation of bile ducts, 375 patients (2.6 percent); stenosing papillitis, 274 patients (1.9 percent); benign stricture of bile ducts, 133 patients (0.9 percent); and others. Malignant tumors were found in 243 patients, of whom 132 (54.3 percent) were not expected to have gallbladder cancer. Accuracy rates for preoperative diagnoses in the patients with gallstones of the intrahepatic or extrahepatic bile ducts or the gallbladder, idiopathic dilatation of the bile ducts, benign stricture of the bile ducts, or benign stenosis of the papilla of Vater were higher than 90 percent. However, the false-negative rates for these six disorders, except gallstones of the gallbladder, were higher than 16 percent. Therefore, despite advances in diagnostic procedures before surgery, intraoperative examinations remain indispensable for determining the most effective approach to surgical repair.

Nicotinamide, a poly (ADP-ribose) synthetase inhibitor, ameliorates B-cell function in partially depancreatized rats

We studied the effect of nicotinamide, a poly (ADP-ribose) synthetase inhibitor, on B-cell functions in 7-week-old male Wistar rats after 90% pancreatectomy (Px). Nicotinamide (0.5 g/kg body wt.) was injected once a day i.p. from 1 week before the surgery, and the injection was continued for 12 weeks after Px. Plasma glucose levels were significantly lower in Px rats treated with nicotinamide (NA rats) than in Px rats without treatment. In in vitro experiments with perfusion of the isolated pancreas, insulin secretion induced by 16.7 mM glucose was blunted in Px rats whereas insulin secretion induced by 19 mM arginine was increased. Nicotinamide treatment restored glucose-induced insulin secretion to normal and partly suppressed the hyperresponse of insulin to arginine. In addition, nicotinamide partially restored the priming effect induced by 28 mM glucose. The insulin content of the perfused pancreas was slightly but significantly greater in NA rats than in Px rats. Histological examination revealed fibrotic degeneration and degranulation in the islets of Px rats, whereas the normal structure was retained in most islets of NA rats. These results suggest that nicotinamide ameliorates islet function in partially depancreatized rats.