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Forty-eight patients with chronic recurrent pancreatitis treated by resection of the head of the pancreas were restudied more than a year post-operatively. In addition to general features such as symptoms, alcohol consumption and work ability, faecal weight, its fat content, fat and fatty acid balance and faecal chymotrypsin were measured. According to the patients' own estimate, late results were good or very good in 70-90%. Faecal fat content and balance indicated high-grade exocrine pancreatic insufficiency in 80 and 90%, respectively. But it was easily controlled by drugs. In a third of the cases there was the need to supplement the diet with medium-chain triglycerides. Its components are satisfactorily absorbed even when the fat utilisation is severely abnormal.

The efficacy and safety of tacrolimus- and cyclosporine-based immunosuppressive regimens were compared in a prospectively defined subgroup of kidney transplant recipients from the European, open, multicentre, 2:1 randomised, parallel group study. Patients were stratified as high risk for immunological events if they had a panel-reactive antibodies grade greater than 80% and/or a previous transplant functional for less than 1 year. The primary efficacy variables evaluated were the incidence of acute rejection, steroid usage and patient and graft survival. Safety was assessed based on adverse events and laboratory evaluations. At 1 year, the tacrolimus group (n = 22) had a lower incidence of biopsy-proven acute rejection (31.8%) and a higher graft survival (86.0%) than the 11 patients in the cyclosporine group (54.5% and 72.0%, respectively). The frequencies of adverse events were similar between the two groups. The tacrolimus regimen appears more beneficial for high risk patients than cyclosporine.

Zusammenfassung Ziel: Vorgestellt wird im Rahmen eines radikalen Konzeptes zur chirurgischen, hyperthermen und chemotherapeutischen Behandlung von Patienten mit Peritonealkarzinose die szintigraphische Überprüfung der Funktion intraperitoneal liegender Katheter zur regionalen intraperitonealen Chemotherapie. Methoden: Zur Verwendung vorgeschlagen wird die Applikation von Tc-99m-DTPA, durchmischt in 500 ml 0,9%iger NaCI-Lösung. Applikationsprobleme, die intraperitoneale Verteilung und der zeitliche Verlauf der Resorption des Tracers werden anhand von 26 Applikationen an 20 Patienten dargestellt. Ergebnisse: Eine Leckage und drei Partialverschlüsse, die sich umgehend revidieren ließen, traten auf. Es zeigte sich, daß über den Peritoneal-Dialyse-Katheter das obere und auch das rechte Abdomen sowie die zentrale Region weniger gut erreicht werden. Im Einzelfall können erhebliche Fehlverteilungen vorliegen: Bis zu 40% des Abdomens bleiben tracerfrei. Schlußfolgerungen: Bei groben Fehlverteilungen ist die Indikation zur erneuten regionalen Chemotherapie sehr zurückhaltend zu sehen. Allerdings lassen sich aufgrund der derzeitigen Datenlage konzeptionelle Rückschlüsse oder Änderungen des individuellen Therapiekonzepts nicht begründen. Denkbar ist, daß bei Patienten mit einer groben Fehlverteilung, insbesondere mit Aussparung der Regionen und konsekutiv gehäuftem Auftreten von Rezidiven, auf die geschlossene Chemotherapie verzichtet werden kann und dann bei Notwendigkeit eine erneute offene Chemotherapie indiziert ist. Das hier vorgestellte Verfahren ist auf einfache, nicht belastende Weise in der Lage, diese Patientengruppe zu erkennen. Im bisherigen Kollektiv waren etwa 20% (4/19 Patienten) betroffen.

In patients with active Crohn's disease and in a control group the fatty acid profiles in the whole lipid fraction of ileal and colonic mucosal biopsy specimens were determined by capillary gas chromatography. The biopsy specimens in Crohn's disease patients were taken from the inflamed terminal ileum as well as from the inflamed and macroscopically normal colon. Compared with controls the fatty acid distribution in the inflamed ileal mucosa was significantly characterised by (a) a decrease of 18:2 n6 and 18:3 n3 accompanied by a substantial increase of the highly polyunsaturated fatty acids 20:4 n6, 22:4 n6, and 22:6 n3 and (b) a higher unsaturation index of total fatty acids compared with controls. These changes were similar in the inflamed colon. Additionally, both the inflamed and the macroscopically normal colonic mucosa showed an increase of saturated (18:0) and a decrease of monounsaturated fatty acids (18:1 n9). Fatty acid profiles of ileum and colon showed side variations in controls, but not in the Crohn's disease group. These data suggest that in Crohn's disease changes in the distribution of polyunsaturated fatty acids seem to be the general feature of inflamed mucosa in small and large intestine. Results further suggest that colonic fatty acid metabolism in Crohn's disease is altered by degrees, showing changes in saturated and monounsaturated fatty acids as an additional, primary event.

Over the past decade various clinical trials have used monoclonal antibodies as therapeutic agents against solid tumours. No consistent pattern of response or improved survival has yet emerged although antigenic heterogeneity and insufficient accessibility of cells in advanced tumours have been offered as explanations for these failures. We designed a study in which a monoclonal antibody was used to target minimal residual disease in an early stage of tumour cell dissemination in patients with colorectal cancer. Only patients in Dukes' stage C who had undergone curative surgery and were free of manifest residual tumour were admitted. 189 patients with colorectal cancer of stage Dukes' C were randomly assigned to an observation regimen or to postoperative treatment with 500 mg of 17-1A antibody, followed by four 100 mg infusions each month. A balance of risk factors in the two groups was achieved by dynamic randomisation procedure. After a median follow-up of 5 years, antibody treatment reduced the overall death rate by 30% (Cox's proportional hazard, p=0·04, log-rank p=0·05) and decreased the recurrence rate by 27% (p=0·03, p=0·05). The effect of antibody was most pronounced in patients who had distant metastasis as first sign of a relapse (p=0·0014, p=0·002), an effect that was not seen for local relapses (p=0·74, p=0·67). Toxic effects of 17-1A antibody were infrequent, consisting mainly of mild constitutional and gastrointestinal symptoms. During 371 infusions four anaphylactic reactions were seen, all controllable by intravenous steroids and none necessitated admission to hospital. Adjuvant therapy with 17-1A antibody extends life and prolongs remission in patients with colorectal cancer of Dukes' stage C.

Surgical therapy still represents the treatment of choice for patients with primary gastric adenocarcinoma, but surgery may have reached its limits concerning the rate of resectability, postoperative mortality and survival rates. Resectability is as high as 80%, mortality after resection ranges between 3% and 5% and the best survival data can be achieved if potentially curative tumor-free (R0-) resection including systematic lymphadenectomy can be performed. Significant prognostic benefits are to be expected in tumor stages II and IIIA. Most gastric carcinomas, however, are diagnosed in far advanced tumor stages (i.e., stage IIIB and IV) and the survival rates in these patients remain disappointing. Multimodality treatment, consisting of preoperative chemotherapy and surgery, may be an encouraging alternative strategy. By endoscopic ultrasonography and staging laparoscopy it may be possible to identify patients with locally advanced tumors, so that these patients should be subjected to multimodal therapy to improve their prognosis. Primary surgical treatment should be exclusively performed in patients with tumor stages up to IIIA and those who are not eligable for aggressive chemotherapeutic regimens, while the concept of multimodality therapy needs to be investigated in the other cases within controlled prospective clinical trials.

Foci of altered hepatocytes (FAH) including clear cell foci excessively storing glycogen (focal hepatic glycogenosis) are well known as preneoplastic lesions in animal models of hepatocarcinogenesis induced by chemical, physical or viral agents. The occurrence of similar lesions has been studied in a series of 67 explanted and 2 resected human livers using histological and histochemical approaches. A high incidence of FAH was found in the liver of patients suffering from hepatocellular carcinoma(HCC, 14/14) and liver cirrhosis (21/42). FAH were also detected in one patient each with inborn hepatic glycogenosis type 1a, and cholangiocellular carcinoma. Two patients with focal nodular hyperplasia had FAH-like enzymatic changes within these lesions. No FAH were found in 5 donor livers. FAH excessively storing glycogen including clear and mixed cell foci predominated in most cases with these lesions. The focal hepatic glycogenosis was associated with a significantly increased cell proliferation compared to the extrafocal parenchyma, and with alterations in the activity of various enzymes. In the 175 FAH studied by enzyme histochemistry, two enzymes involved in glycogen breakdown, namely glycogen phosphorylase and glucose-6-phosphatase, showed the most consistent changes, being reduced in 98% and 95%, respectively. In addition, the activities of adenosine triphosphatase and gamma-glutamyltransferase were reduced in 46% and 53% of FAH, respectively. Inconsistent changes were observed in FAH concerning a number of other enzymes. The 14 HCCs investigated histochemically often contained clear cell populations rich in glycogen in well differentiated portions, but were poor in glycogen in moderately and poorly differentiated tumors or tumor components. There were some similarities in the enzyme histochemical pattern of HCC and FAH but also important differences were evident. In contrast to FAH, all HCCs (except one carcinoma of the fibrolamellar type) showed an increase in the activity of the mitochondrial glycerol-3-phosphate dehydrogenase, and 50% of the cases had increased glucose-6-phosphate dehydrogenase activity. The activities of glucose-6-phosphatase and gamma-glutamyltransferase usually showed a reactivation, or even an increase compared to the extrafocal parenchyma, in moderately and poorly differentiated HCCs. Our results indicate that the focal hepatic glycogenosis is a putative preneoplastic lesion in human beings similar to laboratory animals. The focal hepatic glycogenosis appears to be a frequent initial step in neoplastic transformation of hepatocytes, a process associated with a fundamental shift in energy metabolism.

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%).

Total gastrectomy is discussed as the operation of choice among different surgical approaches for gastric carcinoma. We prefer the performance of an elective total gastrectomy with systematic lymphadenectomy (compartments I and II) and obligatory splenectomy. A retrospective study of 1,704 consecutive cases of gastric carcinomas showed a better outcome following total gastrectomy in relationship to distal subtotal gastrectomy, but these results cannot be used as evidence because of the lack of a prospective study. Nevertheless, a precise analysis of our cases in regard to tumor site and tumor type could show a frequency of only 6% to maximally 30%, in which elective total gastrectomy may represent a procedure too extensive to justify for an oncological course.

Blood ciclosporin (Cs) metabolite pattern in 58 liver grafted patients was routinely monitored by HPLC from the first Cs dose after transplantation until discharge from hospital. Eighteen patients with normal kidney function were allocated to Group I and 14 patients in Group II suffered Cs nephrotoxicity during their clinical course. There were no significant differences between both groups in blood Cs level, kidney function before transplantation, liver function or co-administration of other potentially nephrotoxic drugs. A correlation matrix involving both groups showed a significant correlation between the blood concentration of metabolite M1c9 and serum creatinine and urea, and an inverse correlation with creatinine clearance. During a nephrotoxic episode the blood concentrations of metabolites M1c9 and M1A were significantly elevated in patients in Group II. Analysis of the time course revealed significantly higher blood levels of M19 and M1c9 in Group II patients compared with those in Group I for the first 10 days after transplantation. Serum creatinine and urea concentrations remained significantly elevated, the creatinine clearance being significantly reduced throughout the period of observation. The elevated blood concentrations of ciclosporin metabolites M1c9 and M19 during nephrotoxic episodes suggest that these metabolites are associated with ciclosporin nephrotoxicity. It could not be decided if the elevated metabolite concentrations were the result of and/or the reason for impaired kidney function.

Two patients with Wilson's disease (WD) underwent orthotopic liver transplantation, one for subacute liver failure and the other for severe oesophageal haemorrhage. After transplantation both patients fully recovered within five months, and copper metabolism returned to normal. Follow-up examinations were continued for 4 and 6 years. Clinical as well as electrophysiological testing in these two patients yielded better results than in most of 12 WD-patients being conventionally treated for a similar period or even longer.

From 1982 to 1987 sixty-three children were treated with cyclosporin A and low dose prednisolone after kidney transplantation. Patient survival rate at 4 years after transplantation was 98.3 %, survival rate of living related grafts 100 % (n = 10), and survival rate of cadaveric grafts 73 % (n = 53). Adequate cyclosporin blood levels were achieved in all children with a dosage regimen related to body surface area. Major concerns during the observation period were the loss of glomerular filtration rate from 51.8 to 40.5 ml/min/1.73 m2, a hypertension rate of 77.8 %, and hyperuricemia. Cyclosporin A-side effects were mild. Infections occurred in 11.1 %. Growth retardation in prepu-bertal children improved by 0.74 standard deviations of normal height, and in pubertal children by 0.51. We conclude that cyclosporin A treatment in children enables excellent long term graft survival rates with improved growth rehabilitation, however, the prevention of the cyclosporin associated nephrotoxicity and hypertension remains the major problem.

Intraoperative peritoneal chemohyperthermia (IPCH) followed by one or more courses of closed intraperitoneal chemotherapy via peritonealdialysis-catheter (Zellermann) is a promising concept for treatment of peritoneal carcinomatosis.To prove the functionality of the catheter a scintigraphic method is introduced using a liquid solution of sodium chloride-- Tc-99m-Diethylenetriaminepentaacetic acid (Tc-99m-DTPA) (500 ml). This study was aimed to look for problems over the period of application and to measure the intraperitoneal distribution and resorption of the fluid.One leakage and 3 revisible obstructions occured in 26 applications done in 20 patients. The upper right and the central abdomen was not reached as extensive as the other regions. The abdomen was divided into 9 regions of equal size. In 4 out of 19 patients (20%) the fluid tracer was missed in more than 3 regions (up to 40% of the total area).It is to early to decide whether methological modifications are necessary in these cases, but closed chemotherapies in patients with maldistribution may not be indicated. This will be in particular necessary if there is a relation between the maldistribution and the location of recurrencies. The demonstrated simple scintigraphic method, however, is able to recognize patients at risk.

Background The proportion of diabetics among patients requiring renal replacement therapy continues to increase in most western countries. The acceptance rate for renal transplantation varies among transplant centers and is influenced by the current opinion on the outcome of transplantation in diabetics. Controlled data on patient and graft survival in type I diabetics, however, are scarce. Methods We performed a retrospective case-control analysis on patient and graft survival and the cardiovascular morbidity of patients with type I diabetes after renal transplantation versus carefully matched non-diabetic transplant recipients. Match criteria were duration of previous hemodialysis, age and date of renal transplantation. Moreover, risk factors for cardiovascular disease in uremic patients were evaluated at the time of registration for renal transplantation and at the end of the observation period. Results Seventy-seven matched pairs were enclosed. Patient survival was significantly worse in the diabetic patients, graft survival was comparable in both groups, when graft loss because of patient's death was censored. In the diabetic patients, risk of death (odds ratio: 4.38) as well as the prevalence of cardiovascular morbidity (odds ratio: 4.47) were significantly higher than in the matched nondiabetic controls. Cox regression analysis showed that diabetes mellitus was an independent risk factor for patient survival; no association was found with hypertension, hyperlipidemia, hyperparathyroidism, calcium x phosphate product, body mass index and HbA1c. Cardiovascular morbidity, however, was already significantly higher in the diabetic group at the time of registration. Conclusions Diabetes mellitus type I has a dominant impact on morbidity and mortality after renal transplantation and is associated with an approximately 4-fold higher risk of death. Cardiovascular disease accounts for the significantly worse long-term outcome of diabetic patients after renal transplantation.

To evaluate the tolerability of single oral SDZ RAD doses in stable renal transplant recipients and the pharmacokinetics of ascending SDZ RAD doses when coadministered with steady-state cyclosporin A microemulsion (Neoral).This randomized, double-blind, placebo-controlled, sequential study involved 54 patients in six treatment groups; a different SDZ RAD dose (0.25, 0. 75, 2.5, 7.5, 15, 25 mg) was assessed in each group. Patients received a single oral dose of SDZ RAD (n=6) or placebo (n=3) with their usual Neoral dose. SDZ RAD and cyclosporin A pharmacokinetic parameters were determined.All SDZ RAD doses were well tolerated, with no discontinuations due to adverse events, serious adverse events, or deaths. Similar proportions of patients receiving SDZ RAD and placebo had at least one adverse event (44% and 50%, respectively). Mean changes in laboratory variables (baseline to endpoint) showed no clinically meaningful differences between SDZ RAD and placebo groups. SDZ RAD was absorbed rapidly and showed dose-proportional pharmacokinetics (dose: 2.5-25 mg), based on systemic exposure. Multiple postabsorptive phases in the pharmacokinetic profile indicate tissue distribution. The elimination half-life ranged from 24 to 35 h across the five highest dose groups. Pharmacokinetics were similar in men and women. Co-administration of escalating single oral SDZ RAD doses did not affect steady-state cyclosporin A pharmacokinetics.SDZ RAD was well tolerated; safety profiles of SDZ RAD and placebo were similar. SDZ RAD pharmacokinetics were dose-proportional across the range 2.5-25 mg in conjunction with cyclosporin A-based therapy, according to systemic exposure. Cyclosporin A pharmacokinetics were not affected by coadministration of single oral doses of 0.25-25 mg SDZ RAD.

The liver plays a central role in the production and metabolism of lipoproteins, regulating their synthesis and degradation. The protein content of the lipoproteins are the so-called apolipoproteins. Some of the apolipoproteins serve as cofactors for enzymatic reactions, as ligands for interaction with specific receptors, and as structural proteins. Apolipoprotein B (apoB) is the primary structural component of the atherogenic low density lipoprotein (LDL) particles and has a specific binding region for interacting with the LDL-receptor. In contrast, apolipoprotein A-I (apoA-I) represents the primary protein content of the high density lipoprotein (HDL) particles, which interacts with the putative HDL-receptor, and stimulates the enzymatic reaction of lecithin-cholesterol acyltransferase (LCAT) resulting in esterified cholesterol, which is the essential step in the process of reverse cholesterol transport.We studied lipid parameters in arterial and hepatic venous serum samples from 52 patients with cirrhosis and from 16 patients in the clinically stable long-term course after liver transplantation. Splanchnic blood flow was measured (indocyanine-green steady-state infusion) and hepatic extraction/production rates were calculated. To assess the influence of the clinical stage of established cirrhosis, the quantitated parameters were statistically analyzed.In cirrhosis, apolipoprotein A-I levels are decreased depending on the clinical stage (p0.01). This parameter showed excellent correlations to liver function tests. Triglycerides (TG) (p0.05) and cholesterol (Chol) (p0.05) were reduced as well, whereas apolipoprotein B levels did not change. In cirrhosis, hepatic production of both cholesterol and triglycerides were decreased (p0.05 each), as well as hepatic extraction of free fatty acids (FFA) (p0.01). Except for cholestatic liver disease with raised serum cholesterol (p0.05) and apolipoprotein B levels (p0.001), the etiology of cirrhosis had no impact on the observed serum lipid alterations.The serum concentrations of the determined lipid parameters depend primarily on liver function. Decreased liver function was associated with reduced extraction of free fatty acids and reduced cholesterol and triglyceride synthesis. Liver transplantation restored the lipid abnormalities to normal. Finally, apolipoprotein A-I served as an excellent parameter for predicting liver function in the studied patients.

The rare event of a benign mesenchymal tumor of the liver is described since its cystic transformation resembled hydatid disease through the presence of Echinococcus. Ultrasound and computerized tomography showed a cystic mass within the liver of a 57 year-old woman with upper abdominal pain. This was interpreted as hydatid disease and an evacuation procedure was performed. The histopathology of a minute specimen was interpreted as consistent with chronic inflammation in a cyst wall. Five years later, a recurrence of the parasite was suspected, and complete excision of the mass and resection of a bile fistula was performed. The histopathological examination revealed a large benign schwannoma with regressive cystic changes, proven by positive immunoreaction for the neurogenic marker S-100 protein. Revision of old paraffin blocks of tissue taken during the first operation was able to retrospectively confirm the identical tumor by the same markers. Occurrence of schwannomas in parenchymatous organs or the retroperitoneum is extremely rare and may lead to asymptomatic growth with cystic changes, causing considerable difficulties in imaging procedures. Overall, the primary complete excision of cystic masses within the liver seems to be the best approach in discovering their real nature and to ultimately cure them.

Angiotensin converting enzyme (ACE) inhibitors have been successfully used for treatment of proteinuria after renal transplantation (RTx). Factors possibly responsible for the great inter-patient variance of the antiproteinuric effect (APE) have not yet been investigated in renal-transplanted patients.28 patients after RTx with a persistent proteinuria of more than 1.25 g/d were treated prospectively with does of fosinopril (10-15 mg/d) which were not effective on systemic arterial blood pressure. Prior to initiation of fosinopril, renal graft biopsy was performed in all patients and renal graft artery stenosis was excluded by duplex ultrasound. Serum creatinine and proteinuria were measured prior to, as well as 3 and 8 months after initiation of ACE inhibition, mean arterial pressure was controlled via 24-h measurement and repeated spot measurements. Reduction of proteinuria was correlated with renal histology, serum creatinine, creatinine clearance, mean arterial blood pressure, sodium excretion before therapy and the relative changes of these parameters during therapy respectively.Therapy had to be stopped in 8/28 patients due to side effects including rise of serum creatinine (n = 4). Three patients were excluded due to non-compliance. In the remaining patients (n = 17) proteinuria was reduced from 2.94 +/- 1.66 to 1.82 +/- 1.39 and 2.48 +/- 3.05 g/d after 3 and 8 months respectively, in the mean +/- SD. There was a significant inverse correlation between the APE and the extent of benign nephrosclerosis, interstitial fibrosis and tubular atrophy. No correlation of the APE to any of the other parameters could be demonstrated.Fosinopril can be administered effectively in a subgroup of proteinuric renal transplant recipients. However, because of a high proportion of patients developing side effects, careful monitoring is obligatory. Our results show that the lesser the degree of chronic morphological injury, the greater is the antiproteinuric effect. Thus, the degree of pre-existing histologically proven damage of the graft may serve as an indicator for the antiproteinuric efficacy of ACE inhibitor therapy after RTx.

Hepatic graft reperfusion is associated with inflammatory processes of unknown relevance to the fate of graft. This study aimed to clarify this relevance by histochemical analyses of human hepatic grafts.Paired tissue samples were taken at the end of cold preservation and 2 hr after reperfusion (n=39). From six additional grafts, biopsies were performed at the end of cold preservation only. Injury or inflammatory markers of sinusoidal endothelium (von Willebrand factor-related antigen [vWF]), Kupffer cells (25F9), platelets (CD62), neutrophil leukocytes (CD11b), interleukin (IL)-1beta, intercellular adhesion molecule (ICAM)-1, and HLA-DR were evaluated semiquantitatively by indirect immunoperoxidase staining. Steatosis was also evaluated by hematoxylin and eosin staining.vWF, CD62+ platelet aggregation, CD11b+ leukocytes, and IL-1beta levels increased after reperfusion, and these levels correlated with prereperfusion levels. Not only vWF, CD62+ platelets, CD11b+ leukocytes, IL-1beta, ICAM-1, and steatosis after reperfusion, but also IL-1beta, ICAM-1, and steatosis before reperfusion correlated with postoperative peak transaminase. Furthermore, vWF, CD11b+ leukocytes, 25F9+ macrophages, and ICAM-1 after reperfusion were associated with primary graft nonfunction and strong expressions of ICAM-1 or HLA-DR with early acute rejection. Although some markers (IL-1beta, CD62+ platelets, and CD11b+ leukocytes) correlated with preharvesting parameters (donor age or length of intensive care unit stay), none showed any significant correlation with cold preservation.Synergistic inflammatory events in the hepatic graft at reperfusion, which have a significant impact on the later clinical course, are largely defined and precipitated by injury or activation of nonparenchymal cells preceding reperfusion or even graft harvesting.

Various techniques of isolated liver perfusions have been described, using hepatic artery or both hepatic artery and portal vein. In this paper the technique of isolated arterial liver perfusion is presented. Twelve patients suffering from non-resectable liver tumors underwent this approach. All of them had been previously unsuccessfully treated by resection or systemic chemotherapy. The liver perfusions were performed without technical problems. No operative death occurred. The mean operating time was 413 +/- 29 min. Although the perfusion medium was oxygenated and the absolute anoxic period was shorter than 10 min in all cases the perfused livers showed a marked postoperative increase of liver enzyme levels. Further studies should be aimed at reducing this hepatic injury and simplifying the complex surgical procedure.

Budd-Chiari syndrome is characterized by hepatic venous outflow obstruction, which often leads to death as a result of portal hypertension and liver failure. Venous decompressive shunt surgery and liver transplantation represent efficient surgical treatments of Budd-Chiari syndrome. In the case presented here, severe intrahepatic compression of the inferior vena cava (IVC) was caused by the hypertrophic caudate lobe. A mere portocaval shunt was not feasible because of a large pressure gradient across the intrahepatic stenosis. A two-step procedure with preoperative radiological dilation and stenting of the intrahepatic IVC followed by a portocaval shunt was successfully performed. Consequently, liver transplantation and its subsequent immunosuppression could be avoided.

Clinical studies revealed that the size of the margin of resection and the microscopic findings at the edge of the specimen did not influence the rate of recurrence. Regarding early lesions of Crohn's disease, the aim of the present study was to identify morphological alterations which are able to explain the clinical findings and are in accordance with the operative procedure. In the present study the resection margins of 29 patients with Crohn's disease were investigated using the scanning electron microscope. Seventy-three percent of patients with histopathologically unaffected resection margins in the small bowel and 71% in the large bowel showed early lesions. These consisted of mucosal architectural alterations, epithelial bridge formation and goblet cell hyperplasia and hypertrophy. Curative resection is not possible, independent of the resection margins. The morphological findings underline the correctness of the usual operative procedure, namely limited resections in Crohn's disease.

Gastrointestinal neuroendocrine tumors are slowly growing and metastases are often limited to the liver. As a result of their favorable biological behavior these tumors have a relatively good prognosis even in metastatic stage. Due to a variety of therapeutic options patients with malignant neuroendocrine tumors may survive for extended periods of time up to ten years. Often a combination of different treatments and also alternation between the different therapeutic regimes is needed. A patient with excessive WDHA-syndrome and severe metabolic disturbances due to a pancreatic VIPoma with metastatic spread into the liver and abundant hormonal secretion is presented. Cytotoxic agents (streptozocin, 5-fluorouracil and adriamycin) were able to alleviate clinical symptoms and to control tumor growth for six years. Analogues of somatostatin (octreotide) and interferon alpha had been very useful in controlling clinical symptoms and tumor progress for 18 months. Cytotoxic agents or octreotide were not able, however, to achieve any permanent cure. Eventually, treatment failure occurred with dramatic progression of symptoms and tumor growth, unresponsive to any medical therapy. Consequently, total hepatectomy and liver transplantation together with extirpation of the pancreatic primary tumor was performed and succeeded in providing a normal life to the patient. In our opinion the overall outcome of patients with metastatic VIPoma may be improved best by maintaining the patients on medical therapy until treatment failure occurs. In case of extended hepatic metastases orthotopic liver transplantation might be considered for patients with symptomatic disease who no longer respond to conventional treatment modalities.

While liver hemangioma and focal nodular hyperplasia are not considered an indication for surgery in asymptomatic patients resection has been recommended for hepatocellular adenoma because of the risk of rupture and malignant transformation. Problems arise from differential diagnosis and the appropriate surgical radicality including the indication for liver transplantation. This retrospective analysis deals with 58 patients who underwent surgery for hepatocellular adenoma: resection of different extension: n = 54, liver transplantation n = 4. In 39.6% of the patients the tumor was an incidental finding. In 62.0% of the character of the lesion was unclear prior to surgery. Tumor rupture and bleeding occurred in 17.2%, malignant transformation in 6.9%. Surgical morbidity was 27.6%, mortality 5.2% with the transplant patients alive for 1.5, 7, 9 and 10 years. Two and five years after resection 2 patients developed hepatocellular carcinoma in the liver remnant. The results confirm the indication for surgery in hepatocellular adenoma. Diagnostic approach for solid liver tumors without serum increase of tumor markers should rule out FNH and hemangioma. In all other patients surgery should be considered whenever possible with the radicality of malignant disease. Liver transplantation can be discussed even in asymptomatic patients with multiple adenoma.

Transactivation of cellular genes and functional inactivation of p53 by the hepatitis B virus (HBV) X gene-encoded protein (HBx) are proposed as alternative mechanisms for induction of hepatocellular carcinomas (HCCs) in chronic HBV infection. Using an immunohistochemical approach, we studied the expression of HBx in 39 explanted livers with HBV-associated disease. Because the data reported previously have been inconsistent, possibly due to the application of different antibodies, we compared results with 5 polyclonal and 6 monoclonal anti-HBx antibodies from five laboratories. Ten of the 11 antibodies reacted with recombinant HBx by Western blotting, but only 1 polyclonal and 2 monoclonal antibodies reacted specifically with HBx in tissue, and were thus suitable for immunohistochemistry. Three other polyclonal antibodies reacted with tissue components in addition to HBx. One polyclonal and 4 monoclonal antibodies did not recognize the HBx in the tissue. HBx was demonstrated in 16 of 30 (53.3%) cirrhotic livers and 10 of 18 (58.8%) HCCs by all specific antibodies. The expression of HBx, among three HBV antigens examined, was found to be preferentially maintained in HCC and the surrounding liver parenchyma, including focal or nodular preneoplastic lesions. However, the immunoreactivity was always limited to the cytoplasm of a small number of parenchymal and neoplastic cells. The role of X gene expression in HBV-associated human hepatocarcinogenesis remains to be established.

To confirm the results of a number of studies conducted in Europe, the United States, and Japan, this multicenter, randomized trial compared the 12-month efficacy and safety of tacrolimus- and cyclosporine-based immunosuppressive regimens in the prevention of renal allograft rejection.A total of 448 renal transplant recipients were recruited from 15 centers and assigned to receive triple-drug therapy consisting of tacrolimus (n=303) or cyclosporine (n=145) in conjunction with azathioprine and low-dose corticosteroids.At 12 months after transplantation, tacrolimus therapy was associated with a significant reduction in the frequency of both acute (tacrolimus 25.9% vs. cyclosporine 45.7%; P0.001 [absolute difference: 19.8%, 95% confidence interval: 10.0-29.6%]) and corticosteroid-resistant rejection (11.3% vs. 21.6%; P=0.001 [absolute difference: 10.3%, 95% confidence interval: 2.5-18.2%]). Actuarial 1-year patient (tacrolimus 93.0% vs. cyclosporine 96.5%; P=0.140) and graft survival rates (82.5% vs. 86.2%; P=0.380) did not differ significantly between the two treatment groups. Overall, the safety profiles of the tacrolimus- and cyclosporine-based regimens were quite comparable. Infections, renal impairment, neurological complications, and gastrointestinal complaints were frequently reported but were mostly reversible in both groups. Higher incidences of elevated serum creatinine, tremor, diarrhea, hyperglycemia, diabetes mellitus, and angina pectoris were reported in the tacrolimus treatment group, whereas acne, arrhythmia, gingival hyperplasia, and hirsutism were more frequent with cyclosporine treatment.The significant reduction in the incidence of episodes of allograft rejection observed with tacrolimus therapy may have important long-term implications given the prognostic influence of rejection on graft survival.

Between December 1968 and July 1995, 2372 renal transplant recipients were seen regularly in our outpatient clinic. 154 patients (6.5%) of these subsequently developed a malignant tumor. One of the most frequently observed malignancies was a renal cell carcinoma in the native kidneys, found in 12 patients (7.8%; i.e. 0.5% of the total population), two of them with analgesic nephropathy and one with adult polycystic kidney disease. So-called acquired cystic kidney disease of the native kidneys was found in 73% of the patients with renal cell carcinoma. In the patients with renal cell carcinoma the median age at transplantation was 43.9 (39-55) yr. The median time from onset of end-stage renal failure and from transplantation to the appearance of the tumor amounted to 117.3 (43-206) and 75.8 (5-164) months, respectively. Despite nephrectomy, four patients died of the cancer (6-57 months). As a consequence we suggest a regular sonographic screening of the native kidneys twice a year in all renal transplant patients. As in dialysis patients, the main risk factors for the development of renal cell carcinoma seem to be so-called acquired cystic disease of the native kidneys and the underlying renal disease, such as analgesic nephropathy, and obviously not the immunosuppressive regimen after transplantation.

Immunosuppressive therapy and its influence on perioperative pathophysiology present special challenges in the event of surgical intervention. Immunosuppressive agents alter the patient's response to surgical stress and infectious complications. The often masked signs, even in the case of severe infection, require a high index of suspicion to establish the diagnosis. This may result in a fatal delay of therapy. In addition, the immunosuppressed state increases the patient's susceptibility to infection and leads to an impairment of wound healing. Therefore, careful perioperative clinical monitoring of the patient and complete control of the immunosuppressive therapy are mandatory. Elective operations in immunosuppressed patients should be performed with special caution regarding the potential perioperative risks for the patient and the graft. On the other hand, if there is evidence of, for example, an acute abdominal event, a more aggressive approach is required to rapidly establish the diagnosis and institute appropriate therapy. From the surgical point of view, special emphasis should be placed on wound closure and on anastomotic sutures when operating on a patient receiving immunosuppressive therapy.

A 59-year old male of German origin noticed exercise-independent cardiac arrhythmia two years before admission. An alanine 47 transthyretin variant of Familial Amyloid Polyneuropathy with hypertrophic cardiomyopathy, peripheral sensory-motor polyneuropathy, I, degree AV heart block was diagnosed. To diminish production and deposition of mutant transthyretin and to prevent disease progression orthotopic liver transplantation was performed. Prior to transplant the patient complained of inappetence. Postoperatively, he received a chemically defined enteral nutrition regime that was discontinued after 30 months until return of appetite and weight gain indicated marked improvement. However, a duodenal biopsy still demonstrated amyloid deposits 24 months after transplantation. Echocardiographic findings remained unchanged. Neurologic examination showed an improvement of sensory-motor polyneuropathy with regression of electromyographic changes. Only traces of variant transthyretin were detectable in plasma samples taken 12 months after the operation. During the 3 year follow-up, no additional symptoms have occurred and progression of amyloidosis was prevented. Currently, orthotopic liver transplantation is the only specific treatment to prevent progression of familial amyloid polyneuropathy.

Microchimerism has been suggested to play an important role in the long-term acceptance of allogeneic organ grafts by transplant patients and for the maintenance of a state of donor-specific low responsiveness. In order to elucidate the kinetics of the development of chimerism we have performed a follow-up analysis in 10 pediatric patients with living-related liver transplantation (LRLTx). Blood samples obtained during the first 6 months and at 18 months post-transplant and skin biopsies taken at one month were analysed for the presence of donor cells by PCR using donor-specific HLA-DRB1 primer pairs or primers for a Y chromosome-specific sequence. Furthermore 13 long-term patients more than 2 yr after LRLTx were studied at two different time points. In the follow-up studies donor cells could be demonstrated in the blood of all patients immediately after transplantation. After a gradual decline all patients became chimerism-negative for several weeks or months. At 6 months, however, in five of eight patients tested and at 18 months in six of nine patients donor cells had reappeared. This biphasic pattern in the development of chimerism is proposed to reflect the occurrence of different donor-derived cell populations in the recipient. The population giving rise to the first wave of chimerism probably represents matured cells with a limited lifespan which are released from the graft into the circulation of the recipient during the first weeks after transplantation. The population of cells occurring with the second wave of chimerism is likely to have been generated by donor-derived cells with stem cell potential located either in the graft or in the hematopoetic organs of the recipient after emigration from the graft. This model may be able to explain fluctuations in the incidence and degree of microchimerism described in other patient populations during the first year post-transplant. Of the 13 long-term patients, chimerism could be demonstrated in 11. In seven patients it was detected in both blood and skin, in three patients the results obtained for blood and skin were discordant. In one patient only blood was analysed. It is not clear whether the negative results really reflected the absence of chimerism or whether the number of donor cells was below the level of detectability.

Owing to increasing limitations on resources in health care, there is an urgent need to investigate effectiveness and efficiency of medical procedures. Therefore, we retrospectively studied the courses of 62 surgical patients who required at least 30 days of intensive care regarding mortality, long-term prognosis and quality of life. Additionally, a cost analysis was made using quality-adjusted life years (QALYs). The hospital mortality was 40.3%. The overall median survival time of discharged patients (n = 37) was 3.7 years and the calculated 3-year survival was 56.4%. The most frequent causes of death were septic complications or multiple organ failure in hospitalized patients and tumor relapses in discharged patients. In most of the surviving patients quality of life (median Gastrointestinal Quality of Life Index: 104 points) was good. About 20% of the discharged patients were able to return to work. Although extended intensive care therapy is extremely expensive (DM 68,250 per QALY), these costs are comparable with other accepted procedures in medicine (i.e. hemodialysis). Therefore, economical aspects should not be a generalized reason for withdrawing or withholding intensive care therapy.

A 41-year-old patient with liver cirrhosis due to autoimmune hepatitis received an emergency transjugular portosystemic stent shunt for uncontrolled acute variceal hemorrhage. Because of markedly impaired liver function, liver transplantation was considered to be indicated and was performed on the following day. Intraoperatively, one of the intrahepatic metal stents migrated unnoticed into the pulmonary artery. The postoperative course was uncomplicated and the displaced stent was left in situ. Eighteen months after the transplantation the patient is well with normal liver function and no pulmonary problems.