Flemming Burcharth

Resection of liver metastases from colorectal cancer: Indications and results

PURPOSE: This study was undertaken to determine the indications for and value of liver resection for metastases from colorectal cancer. METHODS: From 1978 through 1991, 66 patients were operated on for liver metastases from colorectal cancer. All patients had had a curative resection of their colorectal cancer. Forty resections of the liver were major anatomic resections. RESULTS: Five patients died in the postoperative period. All resections were intended to be curative, but in 16 of the patients the resection became noncurative. None of these patients lived more than two years after liver resection. Fifty patients with a curative resection had a three-year survival rate of 36 percent, postoperative death included. Recurrence in the liver was observed in 30 patients (60 percent) from 3 to 33 (median, 11) months after the liver resection. Four patients had repeated resections performed. Two of them are alive without recurrences 34 and 60 months after the first liver resection, respectively. The difference in survival between curative and noncurative liver resection was highly significant (P=0.01). CONCLUSIONS: Sex, age, Dukes stage of primary colorectal cancer, synchronous or metachronous appearance of metastases, or number of metastases could not predict long-term prognosis. The only factors of predictive value were tumor size less than 4 cm in diameter, a free resection margin, and no extrahepatic tumor. If it is possible to do a curative resection, there should be few contraindications against liver surgery as it is the only treatment that can demonstrate long-term survival for approximately one-third of the patients, and it is the only possibility of a cure.

Somatostatin v placebo in bleeding oesophageal varices: randomised trial and meta-analysis.

Abstract Objective: To study whether somatostatin or its derivative octreotide is more effective than placebo for treating bleeding oesophageal varices. Methods: Randomised, double blind trial and meta-analysis with blinded analysis of data and writing of manuscripts. Setting: Departments of medical and surgical gastroenterology in Copenhagen. Subjects: Patients suspected of bleeding from oesophageal varices and of having cirrhosis of the liver. Main outcome measures: Survival, number of blood transfusions, and use of Sengstaken-Blakemore tube. Results: 86 patients were randomised; in each group 16 died within six weeks (95% confidence interval for difference in mortality —19% to 22%). There were no differences between those treated with somatostatin or placebo in median number of blood transfusions (8 v 5, P=0.07, 0 to 4 transfusions) or in numbers of patients who needed balloon tamponade (16 v 13, P=0.54, -11% to 28%). In a meta-analysis of three trials involving 290 patients somatostatin had no effect on survival compared with placebo (P=0.59, odds ratio 1.16; 0.67 to 2.01). For blood transfusions and use of balloon tamponade there was heterogeneity between the trials with no convincing evidence in favour of somatostatin. No placebo controlled trials have been performed with octreotide. Conclusion: Within the limited power of this study and meta-analysis we were unable to show a clinical benefit of somatostatin in the emergency treatment of bleeding oesophageal varices. Key messages Key messages This study failed to show a benefit of somatostatin Meta-analysis of the placebo controlled studies also failed to show a benefit Treatment with somatostatin or octreotide cannot be recommended at present Larger studies are needed to give a definitive answer

Endoprosthesis for Internal Drainage of the Biliary Tract: Technique and Results in 48 Cases

In 48 patients with obstructive jaundice caused by unresectable lesions, a polyethylene tube was inserted into the biliary tract using a percutaneous transhepatic technique. This endoprosthesis provided permanent internal drainage without an external catheter. In 27 patients, bilirubin declined to anicteric or subicteric levels and pruritus subsided. In six patients, endoprosthesis had an intermediate effect, with moderate falls in bilirubin and improvement of their general condition. This method does not seem to increase the risk of percutaneous transhepatic cholangiography, which precedes insertion. It is recommended for patients with inoperable bile duct obstruction and may replace surgical biliodigestive anastomoses in patients with unresectable lesions.

Prevalence of hepatobiliary dysfunction in a regional group of patients with chronic inflammatory bowel disease.

A regional group of outpatients with chronic inflammatory bowel disease (ulcerative colitis, n = 396, and Crohns disease, n = 125) was biochemically screened to estimate the prevalence of hepatobiliary dysfunction. Among the 396 patients with ulcerative colitis, 69 (17%; 95% confidence limits, 14-22%) had at least 1 abnormal laboratory value. Serum bilirubin was elevated in 5%, alkaline phosphatases in 8%, aspartate aminotransferases in 4%, and alanine aminotransferases in 8% of the patients. Two per cent had decreased plasma coagulation factors (2.7 and 10) and serum albumin. Further diagnositc evaluation consisting of ultrasonography, liver biopsy, and endoscopic retrograde cholangiography was performed in patients who had biochemical values more than twice the upper normal limit in two consecutive blood tests within a fortnight. Six patients (1%) fulfilled this criterion. Three patients had primary sclerosing cholangitis, of whom two were primarily diagnosed; one patient had cholangiocarcinoma also primarily diagnosed; and two patients were found to have alcoholic hepatic damage. Among the 125 patients with Crohns disease, 38 (30%; 95% confidence limits, 23-38%) had at least 1 abnormal laboratory value. Serum bilirubin was elevated in 2%, alkaline phosphatases in 18%, asparetate aminotransferases in 3%, and alanine aminotransferases in 10% of the patients. One per cent had decreased plasma coagulation factors (2.7 and 10) and serum albumin concentrations. Three patients (2%) fulfilled the criteria for further evaluation as described above. One patient appeared to have epithelioid granuloma in the liver and one patient had alcoholic liver disease, whereas one patient refused further examination.(ABSTRACT TRUNCATED AT 250 WORDS)

Frequencies and prognostic role of KRAS and BRAF mutations in patients with localized pancreatic and ampullary adenocarcinomas.

Objectives The frequencies and prognostic role of KRAS and BRAF mutations in patients operated on for pancreatic ductal adenocarcinomas (PDACs) and ampullary adenocarcinomas (A-ACs) are scantily studied. Methods KRAS and BRAF mutations were analyzed in formalin-fixed, paraffin-embedded tumor samples from primarily chemotherapy-naive patients operated on with radical intentions for PDAC (n = 170) and A-AC (n = 107). Results Eighty percent of PDAC patients had KRAS mutations (codon 12 mutations: 74%) and 67% with A-AC (codon 12 mutations: 54%). BRAF mutations were less common, 16% in PDAC and 12% in A-AC, and no V600E mutations were found. Fourteen percent with PDAC and 7% with A-AC had mutations in both KRAS and BRAF. Multivariate analysis, including KRAS status, stage, and American Society of Anesthesiologists physical status classification system score, demonstrated that KRAS mutations in patients with A-AC were associated with short recurrence-free survival (RFS) (hazard ratio, 2.45; 95% confidence interval, 1.19–5.06; P = 0.015) and overall survival (OS) (1.93, 95% 1.12–3.31; P = 0.018). KRAS mutations in patients with PDAC were not associated with RFS and OS. BRAF mutations were not associated with RFS and OS. Conclusions KRAS mutations frequencies were high in PDAC and A-AC. KRAS mutations were associated with poor prognosis in patients with A-AC, but not in patients with PDAC.

Ultrasonically Guided Percutaneous Implantation of Iodine-125 Seeds in Pancreatic Carcinoma

Cancer of the pancreas is most often not diagnosed before it has reached unresectable stages. The development of effective palliative treatment for these patients and for those with recurrence after resection is clearly needed. The present study reports the results of ultrasonically guided percutaneous implantation of 125I seeds in 19 patients with cancer of the pancreas. Twelve patients had further adjuvant external radiation. Despite satisfactory seed placement and delivery of the planned radiation dose in most cases, clinical improvement was lacking or only slight and short-lived. No difference in survival or palliation was observed between patients treated with seeds alone compared with patients treated with seeds and external radiation. Survival after seed implantation was short (median 140 days, range 7-401 days). Ultrasonically guided percutaneous implantation of 125I seeds cannot be recommended in the treatment of unresectable carcinoma of the pancreas.

CT for Assessment of Pancreatic and Periampullary Cancer

Over a period of 2 years, 77 patients, strongly suspected of having pancreatic cancer, had abdominal CT as part of the diagnostic work-up. The CT images were reviewed by 2 radiologists who did not know the clinical course, the surgical procedure, or the final diagnosis. The positive predictive value of CT for the diagnosis of pancreatic cancer was 92% (82–97%) and the negative predictive value 69%) (41–89%). The 95% confidence limits of the positive predictive value of CT in staging the extent of periampullary cancer in 52 patients varied between 21 to 79% and 59 to 100%, with the lowest values in diagnosis of liver metastases. The confidence limits for the negative predictive values in staging varied between 17 to 56% and 67 to 94%, with the highest values concerning liver metastases. We conclude that CT cannot be used as the only diagnostic procedure for confirming or excluding the diagnosis of pancreatic or periampullary cancer, and that the staging of periampullary cancer by CT alone is too inaccurate for the evaluation of resectability.

THE COLOSTOMY PLUG: A NEW DISPOSABLE DEVICE FOR A CONTINENT COLOSTOMY

A new disposable device for colostomy control is described. It is a two-piece system consisting of an adhesive base plate and a disposable colostomy plug, attachable to the plate. The plug is made of a soft, pliable plastic material with open cells, containing a carbon filter which allows flatus to pass odour-free. It is packed and compressed in a water-soluble film, which disintegrates immediately after insertion, allowing the plug to expand and prevent the passage of faeces. The device has been tested in 53 patients. Faecal continence and the passage of flatus without noise or odour was achieved in 90%. The median application period until the plug became obstructed with mucus or faeces was 8 h (range 5-24 h or more), the application period being somewhat longer for patients who used bowel irrigation. Patients not using bowel irrigation applied a colostomy bag during the night.

Pancreatic Pseudocysts during First Attack of Acute Pancreatitis

One hundred and forty-eight patients admitted with their first episode of acute pancreatitis were examined by ultrasonography. During the acute attack 1 or more pseudocysts were found in 19 patients (13%), pancreatic abscess in 2, whereas 127 had a normal or swollen pancreas. Two small cysts resolved spontaneously, eight were cured after ultrasonically guided needle aspiration or catheter drainage, and cystogastrostomy was necessary in four cases. One patient refused treatment. Abscesses requiring surgical drainage developed in four of the patients with pseudocysts. The study showed that pseudocysts may appear as early as within 1 week of the first episode of acute pancreatitis. Some pseudocysts may resolve spontaneously, and ultrasonically guided aspiration or drainage may cure approximately half of the pseudocysts.

Pancreatic Secretion of Zinc and Copper in Normal Subjects and in Patients with Chronic Pancreatitis

Pancreatic secretion of zinc and copper in duodenal juice were measured in 7 healthy persons and in 9 patients with chronic pancreatitis. Stimulation with cholecystokinin and secretin increased secretion of zinc in healthy persons but not in patients. Copper secretion was not influenced. In patients with chronic pancreatitis, the correlations between zinc secretion, and amylase and trypsin secretion were significant while in healthy subjects they were not. Possibly pancreatic zinc secretion in the duodenal juice might be used as a measure of exogenic pancreatic function, and determination of zinc in duodenal juice may replace enzyme determinations in the diagnosis of chronic pancreatitis.