Perfusion cholangiomanometry with papillary stimulation by dilute hydrochloric acid.

A modification of cholangiomanometry in which the papilla of Vater was stimulated by hydrochloric acid was devised as a means to evaluate the papillary function. Manometric tracings could be classified into four patterns according to the mode of response to hydrochloric acid of the papilla. Pattern I was the type in which a group of regular, high-amplitude spikes appeared within 60 seconds after the onset of perfusion. This represented a normally functioning papilla. Pattern II was characterized by rhythmic occurrence of low-amplitude waves. This represented a reversible papillitis as evidenced by the fact that postoperatively such cases exhibited pattern I results as examined through T tube. In pattern III the perfusion pressure remained flat, showing no reaction waves. This represented an incompetent papilla. The pattern III patients with conditions which were reversible responded to intravenous pentazocine. In pattern IV the perfusion pressure continued to increase without reaction waves, representing cicatricial stenosis of the papilla or incarcerated stone in the papilla. This method of cholangiomanometry was thus found to be useful for selecting candidates for sphincteroplasty.

Undifferentiated carcinoma of the duodenal ampulla.

This report demonstrates a case of undifferentiated carcinoma of the duodenal ampulla. A 74-year male experienced jaundice lasting for 3 weeks. An upper gastrointestinal series demonstrated a polypoid, ovoid filling defect in the second portion of the duodenum, and duodenoscopy disclosed a protruding mass involving the orifice of the papilla of Vater. Cholangiography demonstrated obstruction due to compression in the terminal common bile duct. Pylorus-preserving pancreatoduodenectomy was performed on the diagnosis of ampullary carcinoma. The gross specimen showed a polypoid mass, measuring 3.5 cm in diameter, in the ampulla, located mainly in the duodenal submucosal layer and invading the terminal common bile duct. Histologically, the tumor was small cell type, undifferentiated carcinoma, arising from the duodenal epithelium adjacent to the ampulla.

Valvuloplasty plus fundoplasty to prevent esophageal regurgitation in esophagogastrostomy after proximal gastrectomy.

To prevent regurgitation esophagitis in esophagogastrostomy after proximal gastrectomy, valvuloplasty plus fundoplasty was carried out in 17 patients with stomach cancer or cancer of the abdominal esophagus. For this purpose, an equilateral triangular flap of 2.5 cm per side was formed at the upper margin of the remaining stomach along the greater curvature. The flap was inverted into the stomach only to serve as a valve. After the esophagogastrostomy was properly performed, fundoplasty was carried out, lifting and suturing the uppermost edge of the stomach to the esophagus along the greater curvature. To prevent pylorospasm as a result of reduced gastric volume, pyloromyotomy was also performed. The results were excellent in those followed for more than 1 year. The technique is simple and effective and, we believe, deserves further clinical evaluation.

Prospective randomized trial of 5-fluorouracil, doxorubicin, and mitomycin C for non-resectable pancreatic and biliary carcinoma: multicenter randomized trial.

BACKGROUND/AIMS: The efficacy of combination chemotherapy, which consists of fluorouracil, doxorubicin and mitomycin, was compared with that of palliative surgery-only in patients (control) having non-resectable pancreatic and biliary carcinomas in a multicenter randomized trial. METHODOLOGY: The patients were assigned to combination chemotherapy consisting of concomitant 5-fluorouracil 200 mg/m2, doxorubicin 15 mg/m2, and mitomycin 5 mg/m2 by intravenous administration. This combination chemotherapy was given concurrently as the initial dose within 1 week after palliative operation, and this regimen was repeated for at least 2 whole courses at 4-week intervals before the next course of therapy. Forty-two cases of this combination chemotherapy group and 41 of the control group were completely eligible for analysis. RESULTS: Regarding the overall 50% inhibition of tumor progression and that of gallbladder carcinoma, there were significantly better outcomes in the modified FAM therapy group. In this group, tumor reduction was achieved in 1 complete response (CR) and 2 partial response (PR) patients. With respect to the overall and differentiated survival times according to the tumor sites and the clinical efficacy, there was no difference between the groups. The most frequent adverse reactions were gastrointestinal manifestations such as anorexia, nausea, vomiting, and diarrhea; also noted was alopecia. CONCLUSIONS: Since this combination chemotherapy inhibited the tumor progression for significantly longer duration and, to a lesser extent, reduced the tumor size in non-resectable gallbladder carcinomas compared to a non-administrated chemotherapy group, this study will function as the basis for pursuing a more effective chemotherapy.

Biliary and urinary excretion of metals in humans.

Fifteen metals (lead, cadmium, arsenic, inorganic mercury, organic mercury, iron, manganese, magnesium, chromium, zinc, copper, nickel, cobalt, tin, and aluminum) were determined in the hepatic bile and urine collected simultaneously from three Japanese individuals (2 males, 1 female). The presence of these metals was classified as follows: hepatic biliary concentrations were higher than urinary concentrations (lead, arsenic, and iron); urinary concentrations were higher than hepatic biliary concentrations (cadmium, inorganic mercury, tin, cobalt, magnesium, chromium, copper, zinc, and nickel); hepatic biliary concentrations were almost equal to urinary concentrations (manganese and organic mercury); and relationship between hepatic biliary and urinary concentrations changed occasionally (aluminum). Eight essential metals (iron, manganese, magnesium, zinc, chromium, copper, nickel, and cobalt) were detected at considerable concentrations in hepatic bile. Accounting for the daily flow volume of hepatic bile and the reabsorption of these metals, the supplementation of these metals should occur during treatment of diseases accompanied by loss of hepatic bile.

[Home anti-cancer therapy with a venous port].

Home anti-cancer chemotherapy and palliation in the terminal stage were performed for patients with advanced cancer of the digestive system, using a venous port implanted beneath the skin via the subclavian vein. Patients under 75 years of age (5 with esophageal, 61 gastric, 59 colorectal, 5 cholangio, 5 pancreatic, 1 hepatic and 1 ileal cancer) were treated. With two portable balloon pumps, continuous intravenous infusion of 5-FU (300 or 400 mg/body/day) combined low-dose injection of cisplatin (5 mg/body/day) was continued for 10 days, and repeated 3 times for 6 weeks. The response rate was 17.9% in 78 patients according to valuation of the tumor mass. In 119 patients also undergoing a tumor marker evaluation, an effect was seen in 26.1%. No severe side effects such as renal dysfunction or bone marrow suppression were seen, and no special infusion was needed. Therefore, such treatment can be continued for a long time. Use of a venous port should make easy the switchover to HPN and the amelioration of the symptoms of the terminal stage, such as pain, and helps patients cope with the worry. Therefore, the present technique is useful in a series of cancer treatments including surgery, chemotherapy and the amelioration of symptoms.

[Prospective randomized trial comparing modified FAM (5-fluorouracil (5-FU) + adriamycin + mitomycin C) versus 5-FU alone for the treatment of non-resectable pancreatic and biliary tract carcinomas (the 1st trial in non-resectable patients). Study Group of Surgical Adjuvant Therapy for Carcinomas of the Pancreas and Biliary Tract].

The modified FAM (5-fluorouracil (5-FU) + adriamycin (ADR) + mitomycin C (MMC)) therapy (FAM group) was compared with 5-FU mono-therapy (F group) by multi-institutional randomized trial in the patients with cancer of the pancreas or the biliary tract who underwent non-resection. The patients in FAM group received 6 mg/m2 of i.v. MMC during operation, 310 mg/m2 of i.v. 5-FU for 5 days in the 1st and 3rd postoperative weeks and 12 mg/m2 of i.v. ADR in the 2nd postoperative week. Those in F group received only 5-FU course in the administration schedule of FAM group. Among the cases which completed respective whole administration schedules. 35 cases in FAM group and 36 in F group, better effect than partial response (PR) was observed in neither groups, and there was no significant difference between groups with respect to overall/each disease survival duration, progression-suppressed duration and clinical effect. Primary adverse effects were alimentary symptoms and hepatic dysfunction, neither of which was serious, and there was no difference between groups except that hair loss was observed in more cases in FAM group (p less than 0.05). Results in FAM group did not statistically surpass those in F group, but a tendency was observed that FAM group was better than F group in terms of survival duration and clinical effect for cancer of the gall-bladder.

[Prospective randomized trial comparing 1/2 FAM (5-fluorouracil (5-FU) + adriamycin + mitomycin C) versus palliative therapy for the treatment of unresectable pancreatic and biliary tract carcinomas (the 2nd trial in non-resectable patients). Japanese Study Group of Surgical Adjuvant Therapy for Carcinomas of the Pancreas and Biliary Tract].

The efficacy of 1/2 FAM, which consists of 5-fluorouracil (5-FU), adriamycin (ADM) and mitomycin C (MMC), was compared with that of palliative treatment in patients with unresectable pancreatic and biliary tract carcinomas in a multicenter randomized trial. The patients assigned to 1/2 FAM group were treated with 5-FU 200 mg/m2/day IV, ADM 15 mg/m2/day IV and MMC 5 mg/m2/day IV. These 3 drugs were given concurrently as the initial dose within a week after palliative operation, and this regimen was repeated for at least 2 whole courses, at 4-week intervals before the next course of therapy. Those randomized to the control group were subjected to palliative treatment alone. Completely eligible for analysis were 42 cases of the 1/2 FAM group and 41 of the control group. There was no significant difference between the groups with respect to the overall and differentiated survival times according to the tumor sites and the clinical efficacy. As for the duration of 50% inhibition of tumor progression, a significantly better outcome was obtained in 1/2 FAM group. Tumor progression was most significantly inhibited in patients with gallbladder carcinoma. In 1/2 FAM group, tumor reduction was achieved in 1 CR and 2 PR patients. The most frequent adverse reaction was gastrointestinal manifestations, along with diarrhea and alopecia. 1/2 FAM did not contribute to the life prolongation, but inhibited the tumor progression for a significantly longer duration and, to a lesser extent, reduced the tumor size in unresectable pancreatic and biliary tract carcinomas. This regimen is suggested to be useful particularly in the treatment of the latter carcinoma.

[Cell kinetic studies on the gallbladder epithelium in patient with anomalous arrangement of pancreatobiliary duct].

It is well known that the patients with anomalous arrangement of pancreatobiliary duct (AAPBD) are combined with biliary tract cancer. To clarify possible carcinogenesis of the gallbladder with AAPBD, DNA analysis of the gallbladder epithelium was performed in control (9 cases), AAPBD (26), gallbladder cancer confined in mucosa (10) and noncancerous epithelium around the gallbladder cancer (21). The mean values of DNA score, as already reported by us as an indicator of cell kinetics, were 12.1 (control), 27.2 (AAPBD, Type a), 13.3 (AAPBD, Type b), 14.8 (noncancerous epithelium around cancer) and 77.2 (gallbladder cancer confined in mucosa). The values of DNA score in the epithelium of AAPBD (Type a) showed significantly high level, which was next to that of cancer. Type a AAPBD may be supposed to have potential malignancy because of its accelerated cell cycle. But as Type b AAPBD without accelerated cell cycle combines cancer at least as often as Type a, further studies should be performed to reveal the relationship between cell cycle and malignancy.

[Pathophysiology of duodenal papillitis in cholelithiasis].

Pathological features of duodenal papillitis relative to cholelithiasis were analyzed in terms of dilatation of the bile duct, intracholedochal pressure, and histopathological pictures of papillitis, and the following conclusions were drawn: The principal causes of bile duct dilatation appeared to be pathological changes in the papilla per se; Papillitis accompanying choledocholithiasis with cholesterol stone were secondary to those gallstones evacuated from the gallbladder; Calcium bilirubinate stones seemed to be formed primarily as the result of papillitis. In some cases, ascariasis in their past history was thought responsible for the papillitis; and 4. It is suggested that as the papillitis advances, papillary incompetence will emerge.

Bile acid composition affecting cholesterol dissolution rate: a use of multiple regression analysis.

The dissolution rate of cholesterol in human gallbladder bile was measured by a rotating-disk method using 14C-labeled cholesterol, and was compared with concentrations of the biliary lipids. Computed multiple regression analysis of the results showed that the dissolution rate of cholesterol could be presented as a function of the concentrations of deoxycholic and chenodeoxycholic acid (multiple correlation 0.905; F-value 51.8 (p less than 0.001)). To examine the effect of different kinds of bile acids on cholesterol solubilization, the cholesterol solubility in a gallbladder bile with addition of a conjugated bile acid was determined. Greater solubilization of cholesterol was observed in the bile with addition of sodium deoxycholylglycine and chenodeoxycholylglycine than that with addition of sodium cholylglycine. There was no additional enhancement of the solubility with addition of sodium ursodeoxycholylglycine. These results suggest that the cholelitholytic effect of chenodeoxycholic acid may be greater than that of ursodeoxycholic acid, since the administration of chenodeoxycholic or ursodeoxycholic acid to patients with cholesterol gallstones induced different alterations of biliary bile acid composition.