Adjuvant combination chemotherapy (AMF) following radical resection of carcinoma of the pancreas and papilla of Vater--results of a controlled, prospective, randomised multicentre study.

Between 1984 and 1987, 61 radically resected patients with carcinoma of the pancreas (n = 47) or the papilla of Vater (n = 14) were randomised either into postoperative adjuvant combination chemotherapy (AMF); 5-fluorouracil 500 mg/m2, doxorubicin 40 mg/m2, mitomycin C 6 mg/m2 (n = 30) once every 3 weeks for six cycles, or into a control group (no adjuvant chemotherapy) (n = 31). The median survival in the treatment group was 23 months compared with 11 months (P = 0.02, median test) in the control group, dependent on a survival benefit in the treatment group during the initial 2 years (P = 0.04 generalised Wilcoxon). The long-term prognosis was the same with an identical survival after 2 years (P = 0.10, power = 0.83). The observed 1, 2, 3 and 5-year survivals in the treatment group were 70, 43, 27 and 4% compared with 45, 32, 30 and 8 in the control group. 1 patient succumbed to sepsis probably attributable to chemotherapy. Cardiotoxicity and nephrotoxicity were recorded in 2 patients. These results suggest that adjuvant chemotherapy does postpone the incidence of recurrence in the first 2 years following radical surgery but increased cure rate was not observed.

Carcinoma of the pancreas and papilla of Vater--assessment of resectability and factors influencing resectability in stage I carcinomas. A prospective multicentre trial in 472 patients.

Between 1984 and 1987, 472 patients with histologically or cytologically verified carcinomas of the pancreas or papilla of Vater, were accrued in the Norwegian Pancreatic Cancer Trial. Surgical assessment revealed resectability in 29% (94 of 330) of the pancreatic tumours and 89% (25 of 28) of the papillar tumours. Tumours of the pancreatic head were resectable in 32% (84 of 259). The sensitivities of the different diagnostic methods in patients with resectable tumours were: FNAC (fine needle aspiration cytology) 80%, ERCP (endoscopic retrograde cholangio-pancreatography) 78%, PTC (percutaneous transhepatic cholangiography) 73%, ERCP with duct cytology 67%, CT (computed tomography) 58%, US (ultrasound) 42% and angiography 22%. The positive predictive values (PV+) in resectable disease were: US 29%, CT 35%, ERCP 43% and angiography 44%. Corresponding figures for unresectable disease were US 95%, CT 97%, ERCP 75% and angiography 88%. Resectable tumours of the pancreas and papilla of Vater had an average macroscopic diameter of 3.2 x 3.4 cm and 2.2 x 2.3 cm, respectively. Tumour size increased with stage. Increasing tumour size and abdominal pain combined with short diagnostic delay both decreased resectability rate, whereas a combination of long diagnostic delay and abdominal pain had a more favorable resectability rate. Radical pancreatic surgery, if effective in the treatment of carcinoma of the pancreas or papilla of Vater, should not be undertaken if any preoperative diagnostic test demonstrates signs of indisputable unresectability. Available methods for the evaluation of resectability in patients lacking such signs are insufficient. This necessitates exploratory laparotomy in many patients.

Carcinoma of the pancreas and papilla of Vater: presenting symptoms, signs, and diagnosis related to stage and tumour site. A prospective multicentre trial in 472 patients. Norwegian Pancreatic Cancer Trial.

During the period 1984-87, 472 patients with histologically or cytologically verified carcinoma of the pancreas (n = 442) or the papilla of Vater (n = 30) were accrued. Diagnostic investigations were performed in accordance with the ordinary routines of 38 Norwegian hospitals. Jaundice at presentation, found in 47% of the patients, indicated a relatively low staging. Abdominal pain or weight loss, present in 72% and 58%, respectively, indicated higher staging. The sensitivities of the diagnostic investigations were 1) endoscopic retrograde cholangiopancreatography (ERCP), 79%, and computed tomography (CT), 75%; 2) ultrasonography (US), 57%; angiography performed in 18% to assess unresectability, sensitivity, 43%; fine-needle aspiration cytology performed in 27%, sensitivity, 86%; and percutaneous transhepatic cholangiography (PTC) performed solely on papillar and head tumours in 16%, sensitivity, 85%. In stage I, PTC and ERCP had a sensitivity of 78%; CT, 52%; and US, 40%. Patient's, physician's, and diagnostic delay averaged 1.8, 2.4, and 4.0 months, respectively. The delays were shortest in stage I and papillar carcinomas.

Tamoxifen therapy in unresectable adenocarcinoma of the pancreas and the papilla of Vater.

Between 1984 and 1987, 176 Norwegian patients with histologically verified unresectable pancreatic adenocarcinoma were randomized to double-blind treatment with oral tamoxifen (30 mg daily; 48 men and 44 women) or placebo (47 men and 37 women). Analysis of oestrogen receptor activity in the carcinomas was not performed. There were no statistically significant differences between the two groups according to age, Karnofsky performance index, tumour node metastasis (TNM) stage, operative treatment or other patient characteristics. The tamoxifen or placebo treatment continued to death or to 10 months after accrual into the trial was stopped. In the tamoxifen group, the mean and median survivals were 205 and 115 days, respectively. These values did not differ statistically from the 192 and 122 days, respectively, observed in the placebo group. Additional retrospective analyses of sex and stage revealed no beneficial effect of tamoxifen upon survival. For women in stage III (any T N1 M0), mean and median survivals were 255 and 191 days, respectively, compared with values of 84 and 45 days, respectively, in the placebo group (P = 0.011). After 2.5 years, three (7 per cent) women in the tamoxifen group were still alive compared with no survivors in the placebo group. No male patients survived beyond 2.5 years. This therapeutic result in a small subgroup of women is probably incidental and not an effect of tamoxifen.

Correlation between gallstones and abdominal symptoms in a random population. Results from a screening study.

A population sample of 2464 persons between 20 and 70 years of age was included in a screening study designed for establishing gallstone prevalence rates and the frequency distribution of abdominal symptoms in groups with and without gallstone(s). The response rate was 55.6%. Two hundred and eighty-five persons had unoperated gallstone disease, as diagnosed by ultrasound. They were compared with 1044 individuals without ultrasonographically detected gallstones. The frequency distribution of epigastric and/or substernal burning, upper or lower abdominal pain, intolerance to fatty food, nausea and/or vomiting, and jaundice was similar for the two groups. Of the screened population 35% have had to see a physician for abdominal symptoms, with no difference between the two groups. In conclusion, abdominal symptoms are common in individuals with and without gallstone(s), but no differences were found in frequency distribution of symptoms between the groups. Consequently, gallstone disease is asymptomatic in the vast majority of individuals. The high proportion of abdominal symptoms in the population with gallstone(s) combined with increasing ultrasonographic activities may lead to unjustifiable cholecystectomies.

Fine-needle aspiration cytology of focal liver lesions. Advantages and limitations.

Fine-needle aspiration cytology of focal liver lesions was performed 192 times in 175 patients over a 5-year period. Ultrasonic guidance was used for 153 punctures; the others were done peroperatively or on a palpable mass. A correct diagnosis of malignancy was obtained in 89/111 cases (80.2%), and of metastases (adenocarcinoma) to the liver in 71/84 (84.5%). The total of nonrepresentative aspirates was 26 (13.5%). The overall accuracy of cytologic evaluation was 87.5%, with 79.5% sensitivity and 100% specificity in malignant disease. The predictive values of positive and negative results were, respectively, 100% and 75.8%. There were no false positive tests, but 12.5% false negatives. No complications following the aspiration procedure were seen. Fine-needle aspiration biopsy is simple and safe, but the relatively high proportion of nonrepresentative aspirates is a problem. Possibly a more aggressive approach with multiple punctures may lessen this incidence and enhance the diagnostic accuracy in hepatic malignancy.

Ultrasonically and fluoroscopically guided therapeutic percutaneous catheter drainage of the gallbladder.

Percutaneous gallbladder drainage was performed in 16 poor surgical risk patients; 13 had acute cholecystitis, 1 had cholangitis and septicemia, 1 had undergone removal of a gallbladder calculus, and 1 had pancreatic carcinoma with bile duct occlusion. Catheterization and drainage of the gallbladder succeeded primarily in all patients. Catheter dislodgement occurred within 24 h in 1 patient without any side effects. One 87-year-old patient died 14 h after the insertion of the catheter from reasons unrelated to the drainage procedure. Percutaneous removal of gallbladder calculi failed in 3 patients, 2 of whom had been successfully treated for cholecystitis by catheter drainage. Percutaneous gallbladder drainage is a fast, low-risk, inexpensive procedure well suited for the treatment of acute, poor surgical risk patients.

Prevalence of gallstones in a Norwegian population.

A population sample of 2464 persons between 20 and 70 years of age was invited to participate in a screening study designed for establishing gallstone prevalence rates. The diagnosis of gallstones was based on an ultrasonographic examination. The overall response rate after the primary invitation was 55.6%. Gallbladder stones were diagnosed in 300 persons, giving a crude prevalence of 21.9%. Total age-adjusted prevalence rates were 17.7% in men and 21.2% in women. From age group 20-29 years to age group 60-69 years the prevalence rates increased from 4.9% to 37.0% in men and from 6.0% to 41.3% in women. The age- and sex-specific rates are comparable to those of more recent studies from Scandinavia but are markedly higher than prevalence rates in a Norwegian study from 1960.

A low molecular weight heparin (KABI 2165) for prophylaxis of postoperative deep venous thrombosis.

In a prospective double-blind trial, low molecular weight (LMW) heparin (KABI 2165) 5,000 U (anti-Xa) once daily was compared with conventional heparin 5,000 IU twice daily, both given subcutaneously, as regards prevention of postoperative deep venous thrombosis (DVT) in 52 patients undergoing major abdominal surgery. Radioactive fibrinogen uptake test (FUT) was used for DVT screening. DVT, diagnosed from positive FUT, developed in two patients from each group, but could be phlebographically confirmed in only one (LMW) case. No intergroup differences were found in peroperative blood loss or requirements for blood transfusion. Complications attributable to the prophylactic regimens were few. In the LMW-heparin group, the anti-Xa levels measured during operation showed considerable variation, the higher activities (greater than 0.30 U/ml) being nonsignificantly associated with increased blood loss. Studies with lower doses of LMW-heparin are recommended.

Budd-Chiari syndrome with obstruction of the inferior caval vein: successful treatment by cavosplenoatrial shunt.

A 27-year-old man had a 10-month history of recurrent ascites, massive edema, and extreme fatigue. The diagnosis of Budd-Chiari syndrome with severe stenosis of the retrohepatic part of the inferior caval vein had been established. Medical treatment had failed to prevent further deterioration. A single 14 mm Gore-Tex graft (W.L. Gore & Associates, Inc. Elkton, Md.) was used to establish a cavosplenoatrial shunt. The postoperative recovery was uneventful. All signs of ascites and edema disappeared within 8 weeks after surgery. In connection with repair of a ventral hernia 8 months later, a liver biopsy specimen revealed partial normalization of liver histology and an angiography demonstrated a patent shunt. Two and a half years after the initial operation he developed a bleeding peptic ulcer demanding emergency surgery. The shunt was again found patent. Three years after the first operation the patient is free of symptoms and working full time.