[Surgical therapy of malignant liver tumors: resection and transplantation].
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to A Weimann.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
OBJECTIVE: This article describes the experience with liver transplantation in patients with irresectable neuroendocrine hepatic metastases. SUMMARY BACKGROUND DATA: Liver transplantation has become an established therapy in primary liver cancer. On contrast, there is little experience with liver transplantation in secondary hepatic tumors. So far, in the majority of patients being transplanted for irresectable liver metastases, long-term results have been disappointing because of early tumor recurrence. Because of their biologically less aggressive nature, the metastases of neuroendocrine tumors could represent a justified indication for liver grafting. METHODS: In a retrospective study, the data of 12 patients who underwent liver transplantation for irresectable neuroendocrine hepatic metastases were analyzed regarding survival, tumor recurrence, and symptomatic relief. RESULTS: Nine of 12 patients currently are alive with a median survival of 55 months (range, 11.0 days to 103.5 months). The operative mortality was 1 of 12, 2 patients died because of septic complications or tumor recurrences or both 6.5 months and 68.0 months after transplantation. all patients had good symptomatic relief after hepatectomy and transplantation. Four of the nine patients who are alive have no evidence of tumor with a follow-up of 2.0, 57.0, 58.0, and 103.5 months after transplantation. CONCLUSIONS: In selected patients, liver transplantation for irresectable neuroendocrine hepatic metastases may provide not only long-term palliation but even cure. Regarding the shortage of donor organs, liver grafting for neuroendocrine metastases should be considered solely in patients without evidence of extrahepatic tumor manifestation and in whom all other treatment methods are no longer effective.
Nef is a regulatory gene product of human immunodeficiency virus type 1 (HIV-1) and other primate lentiviruses which enhances virion infectivity by an unknown mechanism. We report here that Nef is detectable at moderate levels in preparations of HIV-1 virions which lack active viral protease (PR). Significantly smaller amounts of intact Nef were present in wild-type virion preparations. Instead, a smaller Nef-related product with an apparent molecular mass of 18 kDa was associated with wild-type virions, indicating that packaging of Nef resulted in cleavage by the viral PR. The presence of the HIV-1 PR inhibitor A77003 during virus production prevented the appearance of the 18-kDa Nef product and caused an accumulation of full-length Nef in virion preparations. Nef associated with comparable efficiency with viral particles produced by the Gag polyproteins of HIV-1 and Moloney murine leukemia virus, indicating that no specific interaction with a virion component is required for the incorporation of Nef. The N-terminal 86 amino acids of Nef were sufficient for packaging into virions. A nonmyristylated form of Nef associated with viral particles with considerably lower efficiency, suggesting that Nef gains access into nascent virions primarily as a consequence of its affinity for membranes. Our results raise the possibility that Nef enhances infectivity directly as a component of the virion.
Human immunodeficiency virus type 1 (HIV-1) incorporates the cellular peptidyl-prolyl cis-trans isomerase cyclophilin A (CyPA), the cytosolic receptor for the immunosuppressant cyclosporin A (CsA). CsA inhibits the incorporation of CyPA and reduces HIV-1 virion infectivity but is inactive against closely related primate lentiviruses that do not interact with CyPA. The incorporation of CyPA into HIV-1 virions is mediated by a specific interaction with a proline-containing, solvent-exposed loop in the capsid (CA) domain of the Gag polyprotein. CsA, which disrupts the interaction with CA, binds at the active site of CyPA. To test whether active-site residues are also involved in the interaction with HIV-1 CA, we used a panel of previously characterized active-site mutants of human CyPA. Expression vectors for epitope-tagged wild-type and mutant CyPA were transfected into COS-gamma cells along with HIV-1 proviral DNA, and the virions produced were analyzed for the presence of tagged proteins. Cotransfection of the wild-type expression vector led to the incorporation of readily detectable amounts of epitope-tagged CyPA into HIV-1 virions. One CyPA mutant with a substantially decreased sensitivity to CsA was incorporated with wild-type efficiency, demonstrating that the requirements for binding to CsA and to HIV-1 CA are not identical. The remaining six CyPA mutants were incorporated with markedly reduced efficiency, providing in vivo evidence that HIV-1 CA interacts with the active site of CyPA.
PURPOSE: To define the prognostic factors after surgical resection of bile duct carcinomas at the hepatic bifurcation. PATIENTS AND METHODS: The retrospective single-center experience details 151 patients after surgical resection of central bile duct carcinoma performed between 1971 and 1995. Tumor removal was accomplished by resection of the bile duct bifurcation either alone (group I, n = 33), in combination with hepatic resection (group II, n = 77), or combined with hepatic and vascular resection (group III, n = 41). Survival analysis was performed by the Kaplan-Meier method and the relationship between each of the clinicopathologic variables and survival was assessed by the log-rank test. Multivariate results were confirmed using Cox regression. RESULTS: The overall hospital mortality rate was 9.9% and depended on the extent of resection (group 1, 6.1%; group II, 7.8%; group III, 17.1%). After exclusion of hospital deaths, the overall patient survival rate was 28.4% at 5 and 15.5% at 10 years, with a median survival duration of 2.05 +/- 0.23 years. Univariate survival analysis identified tumor size, lymph node metastases, residual tumor stage, and tumor grading as factors with a statistically significant prognostic impact. Survival prognosis was not influenced by the site of the tumor according to the classification of Bismuth and Corlette, extent of resection, International Union Against Cancer (UICC) stage, perineural and vascular invasion, age, or sex. In a multivariate Cox analysis, only lymph node metastases and residual tumor stage proved to be of independent prognostic significance. CONCLUSION: Resection of central bile duct carcinoma is feasible in many patients and a favorable outcome after resection is mainly determined by curative resection and the absence of lymph node metastases.
PURPOSE: The indication for liver transplantation in malignant liver tumors has been controversial due to disappointing results and shortage of donor organs. The authors evaluated the experience and results of a single center in order to define present indications and selection criteria in hepatobiliary malignancy. PATIENTS AND METHODS: Retrospective analysis of 212 patients who underwent liver transplantation for malignant tumors between 1972 and 1995: Primary hepatobiliary tumors: hepatocellular carcinoma, n = 124 (with underlying cirrhosis, n = 86; fibrolamellar subtype, n = 8); intrahepatic bile duct (cholangiocellular) carcinoma, n = 24; proximal bile duct carcinoma, n = 29; other uncommon entities (n = 15); secondary liver tumors: neuroendocrine, n = 11, and nonendocrine, n = 9. RESULTS: Survival rates in primary liver cancer were correlated to International Union Against Cancer (UICC) tumor stage. For hepatocellular and proximal bile duct carcinoma significantly better outcome was found in UICC-tumor stage I and II versus III and IV. No long-term survival was found after transplantation for intrahepatic bile duct carcinoma, hemangiosarcoma and nonendocrine liver metastases. Comparison of transplant and resected patients with hepatocellular carcinoma stage I and II with underlying cirrhosis showed better survival after transplantation: 1-, 3-, 5-year survival rate of 83.3% versus 76.9%, 75.8% versus 44.0%, 60.6% versus 44.0%, and median survival 96.5 versus 23.2 months. Although this difference was not significant, no patient died from tumor recurrence in the transplant group versus three in the resection group. DISCUSSION AND CONCLUSIONS: Patients with malignant tumors can be selected for transplantation with predictable likelihood for long-term survival. According to the present data, liver transplantation can be considered in unresectable UICC-stage II hepatocellular and proximal bile duct carcinoma, the uncommon entities fibrolamellar carcinoma, epitheliod hemangioendothelioma and hepatoblastoma as well as liver metastases from neuroendocrine tumors. UICC-stage II and IV hepatocellular carcinoma as well as intrahepatic bile duct carcinoma, hemangiosarcoma and metastases from nonendocrine tumors should be excluded from transplantation alone. For hepatocellular carcinoma, multimodality treatment protocols have had a proven impact on the prevention of early recurrence and prolongation of survival. There is evidence that liver transplantation in still resectable hepatocellular carcinoma with underlying cirrhosis might be more appropriate in order to cure the cancer-bearing disease.
Cholangiocarcinoma is the second most frequent malignant tumor, after hepatocarcinoma, of the liver; it is diagnosed in approximately 10% of the cases. This retrospective study reviewed follow-up in 50 patients with intrahepatic cholangiocarcinoma treated from June 1979 through February 1993. Among these 50 patients, 32 underwent liver resection and 18 had a liver transplantation. After resection, the median survival was 13.9 months. Tumor stage was seen to have an effect on the Kaplan-Meier plots although the differences were not significant. Four patients died from tumor recurrence more than five years after curative resection, 4 patients are living today. After transplantation, the median survival was 5 months. Among the 18 patients, 1 recipient who had a stage II tumor is currently living 42 months after transplantation with no evidence of recurrence. Despite the high degree of malignancy of intrahepatic cholangiocarcinoma, a certain number of patients do benefit from liver resection, justifying this aggressive surgical approach. Inversely, transplantation does not appear to be an exceptional therapeutic alternative. In the future, cholangiocarcinomas will require multimodal therapeutics.
This report describes the application of intraoperative ultrasound at the explanted liver during ex situ liver surgery. A 55-year-old woman underwent extracorporeal liver resection for multilocular metastases of a duodenal leiomyosarcoma. At surgery, routine intraoperative ultrasound (5-MHz probe) was performed before hepatectomy at the completely mobilized but still normally perfused liver. After hepatectomy ultrasound of the liver was repeated at the back table. By use of the ultrasonographic examination at the back table all the metastases seen with usual intraoperative ultrasound could be confirmed. In addition, one metastasis with a diameter of 6 mm was detected which had neither been suggested by peroperative computer tomography and sonography nor by intraoperative ultrasound or surgical exploration. In cases of extracorporeal liver surgery the combination of in situ and ex situ sonography may improve the identification of hepatic metastases.
Early enteral nutrition is widely accepted for its support of organ structure and function ("gut injury hypothesis") and reduction of infectious complications and hypermetabolism in critically ill postoperative or postinjury patients. Nineteen severely injured patients (Injury Severity Score 40.3 +/- 11.6) were studied for the feasibility of early enteral nutrition via a duodenal feeding tube. Despite maxillary fractures, rhinoliquorrhea and blunt abdominal trauma the enteral feeding was mostly started immediately after trauma. Intermittent diarrhea or constipation resolved after reduction of the feeding rate within 1 or 2 days. Total enteral nutrition could not be realized in all cases; a central venous line was always additionally necessary. However, the goal was not complete enteral nutrition but a continuous enteral supply to maintain the integrity of the gut. The study has shown that early enteral nutrition via a duodenal feeding tube is also feasible in severely injured patients. The expenditure to overcome the technical and organizational problems seems to be justified. Enterally fed patients may have a better outcome that those in whom only parenteral is employed.
OBJECTIVES: The authors evaluated the experience and results of a single center in surgical treatment of proximal bile duct carcinoma. SUMMARY BACKGROUND DATA: Whenever feasible, surgery is the appropriate treatment in proximal bile duct carcinoma. To improve survival rates and with special regard to liver transplantation, the extent of surgical radicalness remains an open issue. PATIENTS AND METHODS: Retrospective analysis of 249 patients who underwent surgery for proximal bile duct carcinoma via the following procedures: resection (n = 125), liver transplantation (n = 25), and exploratory laparotomy (n = 99). Survival rates were calculated according to the Kaplan-Meier method, uni- and multivariate analysis of prognostic factors, and log rank test (p < 0.05). RESULTS: Survival rates after resection and liver transplantation are correlated with international Union Against Cancer (UICC) tumor stage (resection: overall 5-year, 27.1%; stage I and II, 41.9%; stage IV, 20.7%; liver transplantation: overall 5-year, 17.1%; stage I and II, 37.8%; stage IV, 5.8%). Significant univariate prognostic factors for survival after liver resection were lymph node involvement (N category), tumor stage, tumor-free margins, and vascular invasion; for transplantation, they were local tumor extent, N category, tumor stage, and infiltration of liver parenchyma. For resection and transplantation, a multivariate analysis showed prognostic significance of tumor stage and tumor-free margins. CONCLUSION: Resection remains the treatment of choice in proximal bile duct carcinoma. Whenever possible, decisions about resectability should be made during laparotomy. With regard to the observation of long-term survivors, liver transplantation still can be justified in selected patients with stage II carcinoma. It is unknown whether more radical procedures, such as liver transplantation combined with multivisceral resections, will lead to better outcome in advanced stages. With regard to palliation, surgical drainage of the biliary system performed as hepatojejunostomy can be recommended.
The regulation of mediator release in human intestinal mast cells is largely unknown. Apart from IgE receptor crosslinking no secretagogues have been described so far. This study examined the effect of two cytokines (c-kit ligand and interleukin 3) and other agonists on human intestinal mast cell function. Cells were isolated from surgery specimens of 47 patients undergoing intestinal resection because of tumours or inflammatory bowel disease. Cell suspensions contained 3.6% mast cells (mean of 50 experiments). After preincubation without or with c-kit ligand or interleukin 3, cells were stimulated by IgE receptor crosslinking, C5a or formyl-methionyl-leucyl-phenylalanine (fMLP). Histamine and sulphidoleukotriene release was measured in supernatants. The sequential stimulation of the cells with c-kit ligand and IgE receptor crosslinking induced the release of high amounts of histamine and leukotrienes, whereas each agonist by itself induced only marginal mediator release. Interleukin 3 induced no release by itself, but enhanced the IgE receptor dependent release, possibly by an indirect mechanism. No significant mediator release was seen in response to C5a and fMLP, even if the cells were pretreated with c-kit ligand. The mediator release, particularly that of leukotrienes, was higher in cells isolated from actively inflamed tissue from patients with inflammatory bowel disease compared with controls. In conclusion, it was found that, apart from IgE receptor crosslinking, c-kit ligand and interleukin 3 regulate mediator release in human intestinal mast cells. The enhancement of mediator release by cytokines may be of particular relevance in the pathogenesis of inflammatory bowel diseases and food intolerance reactions.
Squamous cell carcinoma of the liver arising from a non-parasitic cyst is a rare entity of a primary liver tumor with an unfavourable prognosis. We report a case of a patient with a cyst in the right lobe leading to upper abdominal symptoms and respiratory discomfort. Malignancy was not suspected from the clinical findings or repeated cytological examination of the cyst fluid. However, the blood stained brown color of the cyst fluid was unusual. Cyst recurrence after six attempts of conservative treatment with sonography guided drainage over a period for more than one year led to laparotomy with cyst unroofing. Because frozen section from the cyst wall revealed the unexpected finding of squamous cell carcinoma right hemihepatectomy was performed during the same operation. The patient is alive more than four years after surgery without cyst or tumor recurrence. The difficulties in establishing diagnosis are confirmed by the review of other reports. In the diagnosis and treatment of symptomatic non-parasitic liver cysts possible malignancy has to be considered. In case of proven carcinoma radical surgery with partial hepatectomy should be performed.
The value of color-coded duplex sonography in the assessment of combined kidney and pancreatic transplantations (KTX/PTX) was studied in 9 patients. In normal graft function the median resistive index (RI) was 0.69 (range 0.60-0.80) for the kidney and 0.61 (range 0.55-0.70) for the pancreas. Ten episodes of graft dysfunction (kidney n = 4; pancreas n = 6) were observed. During renal rejection and hemolytic uremic syndrome the RI was above 0.80. In pancreatic rejection the RI exceeded 0.80 while all other causes of pancreatic dysfunction were not associated with changes in the RI. Color-coded duplex sonography may prove to be a reliable noninvasive diagnostic method in the evaluation of the posttransplant course after combined KTX/PTX, in particular in the diagnosis of pancreatic rejection.
A review of the recent literature about liver cancers shows the increasing role of hepatitis C as a risk factor for the development of hepatocellular carcinoma. A new discussion has arisen with regard to the association between the use of oral contraceptives and hepatocellular carcinoma. Patients at risk for developing liver cancer can be identified and should undergo thorough follow-up to detect cancer at an early stage. Surgical resection remains the treatment of choice whenever feasible. Because of disappointing results and limited availability of donor organs, liver transplantation must be considered only in selected patients with unresectable tumors. There are also arguments recommending transplantation in early resectable hepatocellular carcinoma in patients with cirrhosis to cure the underlying cancer-bearing disease. Improvement of survival can be expected by promising multimodality treatment protocols that have been started during the past few years. Further studies should also investigate the role of immunosuppression in the treatment of tumor recurrence. For patients excluded from resection and transplantation, the most effective treatment options are transarterial chemoembolization and, in small lesions, percutaneous ethanol injection therapy. In small tumors, combination therapy seems to be even more appropriate.
Successful use of laparoscopic cholecystectomy requires good cooperation between surgeon and gastroenterologist. Standard preoperative workup includes detailed history of the patient, blood chemistry of serum bilirubin and liver enzymes as well as sonography for the detection of common bile duct stones. Intravenous cholangiography can be performed to diagnose anatomic variations of the bile ducts. In case of common bile duct stones "therapeutic splitting" by endoscopic retrograde cholangiography with sphincterotomy and gallstone extraction preoperatively may help to avoid unnecessary conventional open cholecystectomy.
Explore the source record for details and available documents.
Occasioned by a recurrent urinary infection, ultrasonography was performed on a 41-year-old otherwise healthy woman. There were no abnormal renal findings, but a 4.5 x 4.5 cm space-occupying lesion with the echo-typical pattern of an haemangioma was found in the right lobe of the liver. Magnetic resonance imaging and dynamic computed tomography demonstrated compression of the vena cava by the tumour which was localized to the caudate lobe. The T2-weighed pictures suggested a cavernous haemangioma which extended from the vena cava at the diaphragm to the portal vein bifurcation. Obstruction to flow became evident 10 months later as oedema of the lower legs, giving the indication for surgical removal of the haemangioma. The benign tumour was enucleated under total vascular occlusion without significant blood loss pre- and post-operatively. The patient was discharged symptom-free on the 13th postoperative day.