Liver transplantation as an option in patients with cholangiocellular and bile duct carcinoma.
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Publications and source records attributed to A Weimann.
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Our personal experience with 172 patients, the results from the European Liver Transplant Registry and a review of the recent literature are summarized and discussed to define present indications for liver transplantation in hepatobiliary malignancy. The following conditions should be considered contraindications: advanced primary liver tumors with any extrahepatic spread, cholangiocellular carcinoma, hemangiosarcoma and liver metastases from nonendocrine primary tumor. Currently, "favorable" indications include uncommon tumors such as fibrolamellar carcinoma, epithelioid hemangioendothelioma, hepatoblastoma and metastases from endocrine tumors. Further indications may be nonresectable hepatocellular and proximal bile duct carcinoma in tumor stage II. Borderline indications are hepatocellular and proximal bile duct carcinoma in tumor stage III. In advanced tumors confined to the liver, transplantation should be restricted to multimodality treatment protocols. Although there are strong arguments for transplantation in early resectable hepatocellular carcinoma with underlying cirrhosis, it remains an open issue requiring further investigation in a controlled study using the same tumor classification. With regard to limited resources of donor organs, split-liver transplantation permits transplantation in tumor patients without neglecting those with benign diseases.
We report on the clinical presentation and diagnostic findings in 45 patients with Budd-Chiari syndrome. The diagnosis was confirmed by histology at the time of liver transplantation (n = 37) or shunt surgery (n = 8). An underlying disorder could be established only in half of the patients, oral contraceptives as predisposing factor were known in 18 cases. Clinically, abdominal pain and distension as well as hepatomegaly and ascites were most frequent findings, whereas changes in laboratory data were more or less unspecific. By use of repeated ultrasound, a definite diagnosis of a Budd-Chiari syndrome could be confirmed in all cases by obligatory demonstration of obstruction or thrombosis of at least one major liver vein. Hepatic venography revealed only one false-negative result. Celio-mesenteric arteriography plus portography, cavography and preoperative liver biopsy did not present additional diagnostic information. These techniques may contribute to treatment planning of portosystemic shunt surgery or hepatic transplantation. In conclusion, the presence of hepatosplenomegaly, ascites, abdominal pain and distension, especially in combination with a known hypercoagulable state, should alert to the possibility of a Budd-Chiari syndrome. Ultrasound is the diagnostic tool of choice. Hepatic venography should only be performed if even repeated ultrasound is not conclusive.
The indication for (obligatory) splenectomy in case of total gastrectomy for gastric carcinoma remains controversial. Overall, an increase of morbidity, but not of postoperative mortality following splenectomy is assumed. Among the prognostic parameters, splenectomy is not an independent indicator. The indication for splenectomy results from the depth of tumor infiltration, tumor site and pattern of lymph node metastases. In T1/2 lesions of the mid-stomach and of the antrum the spleen may be preserved, but splenectomy should be performed in all advanced tumors, carcinomas of proximal sites and infiltration of the spleen. Surgical radicality may be further increased by simultaneous left pancreatic or left upper quadrant resection.
Fifty-two fluid collections following hepatic surgery were diagnosed in 46 patients, mostly by sonography. These were treated percutaneously. In 7 patients ultrasound-guided puncture was used, in 36 patients catheter drainage was employed and in three drainage was instituted by a catheter in a pre-existing fistula. One patient with a bile leak in the hilar region had to undergo surgery. One patient died of multi organ failure following liver transplantation and another patient with advanced tumour died 78 days after the drainage procedure. The other patients recovered following conservative treatment (93.5%).
In order to investigate the diagnostic value in differential diagnosis of primary liver tumors, color Doppler sonography was used preoperatively in 30 patients. Without difference, tumor hypervascularization was found in patients with hepatocellular carcinoma (2 of 4), cholangiocellular carcinoma (4 of 4), hemangioma (3 of 8), focal nodular hyperplasia (8 of 8), adenoma (3 of 4), and neuroendocrine tumor (n = 1). No vascular signal could be detected in 1 case of adenomatous hyperplasia and 2 cases of hepatocellular carcinoma, one after previous chemoembolization. Hemangioma appeared hypo- or even avascular in 5 of 8 patients. Therefore, according to our experience, the yield of color Doppler sonography is rather low for differential diagnosis and prediction of the tumor dignity. With regard to the surgical procedure, valuable information about tumor extension can be obtained particularly in central lesions close to hilar structures or liver vein confluence. Further indications result from follow-up of tumor vascularization after chemoembolization and chemotherapy.
A rare case of Cruveilhier-Baumgarten syndrome with exceptional deep subcutaneous portosystemic collaterals is reported. Undetected these anastomoses represent potentially dangerous sites for hemorrhage complications. Ultrasound in combination with color-coded duplex sonography is a reliable technique in identifying portosystemic anastomoses as well as in providing valuable information about the etiology of portal hypertension.
Body composition and energy expenditure were investigated before and 10-14 days after surgery in 44 patients with upper gastrointestinal cancer (23 esophageal and 21 gastric cancer) in order to assess the impact of preoperative weight loss on metabolic adaptation to the surgical trauma and on postoperative complications. Patients were divided in three groups with I: 0-5%, II: 5-10% and III: greater than 10% preoperative weight loss related to the usual body weight. 50% of the patients presented with no or just minor weight loss. Even in case of weight loss greater than 10% no decrease below the ideal body weight was observed. Body cell mass and fat mass were significantly (p less than 0.05) reduced in group III when compared with I. Since energy expenditure and substrate oxidation rates were rather normal in most patients weight loss was considered to be due to tumor related stenosis and dysphagia. More than 50% of the energy requirements were gained from fat oxidation. General criteria of malnutrition were not fulfilled. Perioperative weight loss was lowest (1.6 +/- 4.9 kg) in patients of group III related to group I (2.9 +/- 1.7 kg) and II (5.0 +/- 6.9 kg). Similar elevation of energy expenditure and lipid oxidation with concomitant reduction in glucose oxidation was observed in all groups of patients. This led to a similar decrease of body cell mass. Independent of preoperative weight loss major complications occurred in 8 cases--pneumonia in 6 and leakage of the anastomosis in 2 patients; no patient died. From this study can be concluded that with regard to perioperative weight loss the metabolic response to surgical trauma is adequate even in patients with marked preoperative weight loss. These patients remain compensated and preoperative weight loss is without major effect on postoperative complication rate.
The treatment of unresectable hepatocellular carcinoma (HCC) by liver transplantation remains controversial. In our series, the 5-year survival value for 87 patients who underwent transplantations between 1972 and 1990 was 19.6%. There was no difference in the long-term survival of patients who had underlying cirrhosis and those who did not. In patients with early-stage tumors the long-term prognosis was improved, the 5-year survival in stage II disease being 55.6% according to UICC criteria. Even in some cases of more advanced tumour stage, good long-term results were obtained. In a review of the recent literature, we evaluated prognostic factors to work out criteria for a more differentiated indication for liver transplantation. Resection of increased radicality--which will keep its place as the therapy of choice--and transplantation should be performed complementarily. Further developments will reveal the value of multimodal therapeutic strategies, including chemo-embolisation, chemotherapy and immunotherapy.
Fibrolamellar carcinoma (FLC) is a tumor of the liver that can be differentiated from common hepatocellular carcinoma (HCC). Despite the exceptional role of the clinicopathologic signs and symptoms, true appraisal of the prognosis of the tumor is not clear and remains a controversial issue. To determine the long term prognosis of FLC more precisely, a retrospective study of 20 consecutive patients was performed, with analysis of selected pathologic factors, particularly the TNM staging system. Curative tumor removal (R0) was achieved by partial hepatic resection in 14 patients and total hepatectomy with subsequent replacement of the liver in six patients, respectively. The estimated overall five year survival rate was 36.6 percent. There was an advantage of partial versus total hepatectomy, with median survival times of 44.5 versus 28.5 months. Statistically significant better survival rates at five years were observed in patients with solitary tumors and in instances of absent regional lymph node metastases. Although other factors analyzed did not show significant differences, there was a tendency indicating individual tumor stage was the most significant determinant for prognosis. For further discussion of an apparently more favorable outcome of patients with FLC as compared with common HCC, detailed specification of the tumor stages seems mandatory. From the present analysis, the fibrolamellar variant could not be confirmed to be an independent indicator of better patient survival. The treatment of choice remains radical operation. The goal can, at best, be achieved by a therapeutic concept including partial as well as total hepatectomy, depending on the stage of the tumor.
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Splenomegaly is a common finding in patients with portal hypertension. In the present study the relation between spleen size and blood flow in the splenic and portal vein was evaluated in 33 patients with alcoholic liver cirrhosis and portal hypertension using pulsed Doppler sonography (Ultramark 9, ATL, Solingen, FRG). There was a significant positive correlation between hilar spleen diameter (HD) and splenic vein diameter (r = .73, p less than .001) as expected as the consequence of portal hypertension. However, a positive correlation between HD and splenic vein flow (SBF) was found (r = .67, p less than .001). Furthermore, there was no negative correlation between HD and flow velocity in the splenic vein (r = .01, n.s.). Portal blood flow (830 +/- 360 ml/min) was fairly constant in spite of considerable variations in SBF (range: 120 to 1200 ml/min). The data of the present study indicate that splenomegaly in patients with liver cirrhosis and portal hypertension is not simply the consequence of portal congestion resulting in decreased SBF. Rather, increased SBF serves to maintain portal blood flow and thereby contributes to portal hypertension. In few patients (15%) SBF increased to more than 11/min may be an important factor for the severity of portal hypertension. Surgical shunt treatment should be adjusted in these patients.
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Tumor-caused weight loss is frequently associated with a high rate of lipolysis and fat oxidation. In order to differentiate the effect of weight-loss from the tumour-dependent regulation of fat metabolism, we studied weight-stable and well nourished patients (ideal body weight 109 +/- 4% (+/- SEM), body mass index 25.1 +/- 0.9 kg/m2). Parameters of lipolysis (glycerol-, fatty acid concentrations) and the calorimetric determined fat oxidation rate of five male tumor patients were examined before and during an euglycaemic insulinclamp (0.2 mU insulin/kg/min). Concomitant with a high rate of lipolysis (glycerol concentration 112 +/- 20 mumol/l, free fatty acid concentration 0.72 +/- 0.13 mmol/l) and fat oxidation (60% of energy expenditure) there was a low normal insulin level (5.9 +/- 0.5 mU/l). Insulin reduced lipolysis and fat oxidation and stimulated glucose oxidation. Weight-stable tumor patients have a high basal rate of lipolysis and fat oxidation; yet the insulin dependent regulation of the fat metabolism is intact, as we have already shown for weight-losing cancer patients.
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In 21 patients resected for gastric or esophageal malignancy an aberrant left hepatic artery from the left gastric artery was found. The study shows that in systematic lymphadenectomy ligation of the left gastric artery distally from the origin can safely preserve an aberrant hepatic artery without impairment of oncological quality. Related to a control group no difference in the number of resected lymph-nodes and the operation time was observed. Postoperatively there was no problem concerning liver function and surgical morbidity. In real-time sonography the aberrant artery could be postoperatively seen precisely in 19%, but duplex signal was found in 63%. Limited visualization in sonography may be caused by technical problems due to anatomy and overlying air from small-bowel reconstruction after gastrectomy.
Body composition, postprandial symptoms, and social performance were assessed in 41 patients who were free of tumors 16 to 63 months (median, 41 months) after total gastrectomy with Roux-en-Y esophagojejunostomy (n = 15) or jejunal interposition (n = 26). There were no significant differences with respect to age, sex, initial tumor stage, interval since operation, and premorbid weight/height2 (body mass index). The lowest postoperative body mass index (BMI) was 72% +/- 3% of the preillness BMI in patients with Roux-en-Y reconstruction and 79% +/- 2% in patients with jejunal interposition (p less than 0.05). At the time of the study the relative BMI was 88% +/- 2% of the preillness BMI in patients with jejunal interposition but only 81% +/- 3% in patients with the Roux-en-Y reconstruction (p less than 0.01). Muscle mass and lean body mass estimated from anthropometric and bioelectric impedance measurements were correlated with sex (p = 0.0001) and with the mode of reconstruction (p = 0.02) independently, which was confirmed by multiple linear regression. The postprandial symptoms were not significantly associated with changes in body composition except for an inverse relationship between Sigstad's dumping score and the extracellular mass/body cell mass ratio (r = 0.553; p = 0.0002). Of the patients under 60 years of age, 10 of 15 patients with jejunal interposition and two of eight patients with Roux-en-Y reconstruction were back at work (p = 0.057). The persons who had resumed their work had a significantly higher relative BMI (90% +/- 2% vs 82% +/- 3%), lean body mass (53 +/- 3 kg vs 46 +/- 3 kg), and muscle mass (25 +/- 2 kg vs 21 +/- 1 kg) than persons in early retirement. We concluded that preserving the duodenal transit should be a main objective of gastric replacement after total gastrectomy.
Emptying of the gastric substitute and small bowel transit time of a 99mTc-labeled solid test meal were measured in 20 tumor-free patients 13 to 63 (median, 35) months after total gastrectomy with Roux-y (n = 11) and jejunal interposition (n = 9) reconstruction. The emptying half-times ranged from 2 minutes to greater than 20 minutes. Rapid emptying was associated with dumping symptoms (p less than 0.03) and shorter orocoecal transit-time (p less than 0.05). Serum glucose concentrations rose more quickly in jejunal interposition, but the areas under the curve were identical in both groups. The median insulin-to-glucose ratio (areas under the curve) during the 20 minutes after the meal was 11.4 in jejunal interposition and 7.1 in Roux-y esophagojejunostomy (NS). Interposition cases had regained a significantly higher percentage (89%) of their premorbid weight than patients with Roux-y (78%; p less than 0.05). The weight/height2 ratio was above the 50th centile in 45% of interpositions, but below the 50th centile in all patients after the Roux-y mode of reconstruction (p less than 0.05). It is concluded that the emptying velocity of the gastric substitute has no impact on postoperative weight gain. The authors contend that the concept of a gastric substitute pouch is not supported by the findings of this study.