Living-related versus living-unrelated kidney transplantation using tacrolimus initial immunosuppression.
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Biomedical subjects
Publications and source records attributed to B Ringe.
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According to its different location, clinical features, treatment modalities and prognosis, intrahepatic cholangiocarcinoma should be well differentiated from proximal bile duct carcinoma. There is no therapeutic measure with curative potential apart from surgical treatment. Partial or extended hepatectomy is the treatment of choice in cholangiocarcinoma. Thereby, hilar resection in combination with hepatectomy is increasingly performed in proximal bile duct carcinomas. In most centers liver transplantation is not considered as a therapeutic option for irresectable cholangiocarcinomas.
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BACKGROUND: Early retransplantation is the therapy of choice in patients with initial graft nonfunction (INF). In rare cases the patients' conditions deteriorate dramatically with severe cardiovascular and/or pulmonary insufficiency while on the waiting list for retransplantation. In this life-threatening situation removal of the graft and temporary portocaval shunt before allocation of a new liver proved to be effective. Our experience with this two-stage hepatectomy and subsequent liver transplantation in patients with complicated INF is reported. METHODS: Hepatectomy was performed in 20 patients with INF associated with severe cardiovascular and pulmonary insufficiency while on the waiting list for emergency liver retransplantation. The mean age was 41.75+/-16.64 years. The time period between primary transplantation and hepatectomy was 2.80+/-2.84 days with a range from 1 to 9 days. RESULTS: Hepatectomy reduced the need for vasopressive agents and improved pulmonary function in the majority of patients. Four patients died before a liver was available due to brain death in one patient and multiorgan failure in three patients. In the remaining 16 patients liver transplantation could be performed after 19.82+/-15.34 hr (range 6.58 to 72.50 hr). Two of the 16 transplanted patients died on the first postoperative day due to multiorgan failure and pneumonia. The remaining 14 of 16 patients survived retransplantation, but 7 died between days 13 and 105 mostly due to sepsis. Seven patients were discharged from the hospital in good condition and show long-term survival. CONCLUSION: Hepatectomy was able to stabilize the cardiovascular and pulmonary function. This study confirms the beneficial effects of hepatectomy and subsequent liver transplantation as a life-saving procedure in patients with INF complicated by cardiovascular and/or pulmonary instability.
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Cholangiocarcinoma is a primary liver tumor arising from the small bile ducts within the liver. According to its different location, clinical features, frequency of metastases, treatment modalities and prognosis, intrahepatic cholangiocarcinoma should well be differentiated from proximal bile duct carcinoma. To date, there is no therapeutic measure with curative potential apart from surgical treatment. Partial hepatectomy is the treatment of choice. It is of overriding importance to achieve microscopically tumor-free margins. However, only few patients treated in an early stage have a prolonged recurrence-free survival or a chance for cure. Liver transplantation is not an alternative therapeutic option for unresectable cholangiocarcinoma, due to early tumor recurrence in almost all recipients. Liver transplantation has a place in preventing cholangiocarcinoma in primary sclerosing cholangitis, although the timing of replacement is still a matter of debate. Results of surgery need further improvement by adjuvant or neoadjuvant treatment protocols.
We investigated the prophylactical administration of liposomal amphotericin B (Ambisome) in the early phase after liver transplantation (LTx). Fifty-eight patients received Ambisome prophylactically after LTx. Ambisome (1 mg kg-1 day-1) was given intravenously for 7 days after LTx. Immunosuppressive prophylaxis was cyclosporin A (CsA) based in 11 patients. Forty-seven patients had a tacrolimus-based immunosuppressive regimen. CsA and tacrolimus dosages were adjusted to trough levels of 150-250 ng ml-1 (EMIT) and 5-15 ng ml-1 (MEIA II) respectively. Three patients died from sepsis due to Aspergillus fumigatus infection. Reasons for a fatal outcome were foudroyant Aspergillus pneumonia in a patient transplanted for fulminant hepatic failure on post-operative day (pod) 8; Aspergillus sepsis with severe endocardidtis in a patient with two retransplantations for graft non/dysfunction on pod 24; and disseminated aspergillosis due to Aspergillus fumigatus in a patient retransplanted for primary non-function (pod 19). All three patients underwent haemofiltration for renal failure. One patient with Candida albicans sepsis (pod 4) recovered under increased dosage of Ambisome (3 mg kg-1 per day). Ambisome (1 mg kg-1 per day) seems to be beneficial against systemic Candida infections. However, the onset of systemic Aspergillus infections could not be prevented. Obviously, higher Ambisome doses appear to be necessary against Aspergillus. We recommend the use of Ambisome (3 mg kg-1 per day) for patients with risk factors such as graft dys-/non-function, retransplantation, haemofiltration and complicated acute liver failure to prevent invasive aspergillosis.
PURPOSE: To optimize and determine the value of dual-phase contrast material-enhanced three-dimensional (3D) magnetic resonance (MR) angiography for preoperative evaluation of the blood supply to the liver. MATERIALS AND METHODS: Dual phase 3D MR angiography of the hepatic arteries and portal vein was performed in 140 patients. In 80 patients, the value of fat saturation, digital image subtraction, an anticholinergic agent, and a high-caloric meal were evaluated. In the next 60 patients, MR angiographic and digital subtraction angiographic (DSA) image quality and diagnostic value were compared. RESULTS: Fat-saturated images were of significantly better quality (P < .01) than non-fat-saturated images. Digital image subtraction was useful in only 23 of 40 patients. The injection of an anticholinergic agent was superfluous, whereas administration of a high-caloric meal helped in demonstration of the superior mesenteric artery and portal vein. Classification on MR angiograms of the arterial blood supply was correct in 57 of 60 patients. All arterial and portal venous lesions were seen on MR angiograms, and MR angiograms had a significantly higher subjective image-quality ranking than did DSA images in the evaluation of the portal vein (P < .05). CONCLUSION: Fat saturation and use of a high-caloric meal improve the results of MR angiography of hepatic vessels. MR angiography was comparable to DSA for evaluation of the arterial system and was superior for demonstration of the portal vein; therefore, MR angiography could replace intraarterial DSA.
PURPOSE: Tumor recurrence is the major limitation of long-term survival after liver transplantation for hepatocellular carcinoma (HCC) or fibrolamellar carcinoma (FLC). Understanding tumor-biologic characteristics is important for selection of patients and for development of adjuvant therapeutic strategies. PATIENTS AND METHODS: The study included 69 patients who underwent potentially curative liver transplantation for HCC/FLC and survived for more than 150 days; minimum follow-up was 33 months. Frequency, localization, and timing of recurrence were analyzed and compared with primary tumor and patient characteristics. RESULTS: Tumor recurrence was observed in 39 patients at 67 locations. Hematogenous spread was the major route of tumor recurrence (87%), and the most frequent sites were the liver (62%), lung (56%), and bone (18%). Parameters associated with recurrence were absence of cirrhosis, tumor size greater than 5 cm, more than five nodules, vascular infiltration, and International Union Against Cancer (UICC) stage IVA. Selective intrahepatic recurrence was found in nine patients (23%); it was associated with highly differentiated tumors, lack of vascular infiltration, and male sex. Recurrence at multiple sites was found predominantly in young patients (< or = 40 years) and for multicentric (> 5) primary tumors. Recurrences were observed within a wide time range after transplantation (43 to 3,204 days; median, 441 days); late recurrences (> 1,000 days, n = 8) were associated with highly differentiated or fibrolamellar tumors and low UICC stages. Surgical treatment was the only therapeutic option associated with prolonged survival after recurrence. CONCLUSION: In transplant recipients, hepatocellular carcinomas vary considerably in their pattern and kinetics of metastases. Tumor cells may persist in a dormant state for long time periods before giving rise to clinical metastases. Surgical treatment of recurrence should be considered whenever possible.
At the time of surgery, occult metastases (micrometastases) are present in more than 50% of colorectal cancer patients, and the liver is the most frequent site of apparent metastatic disease. Frequently, adjuvant chemotherapy is unable to prevent tumor recurrence. Thus, novel therapeutic strategies are warranted. The aim of this study was to establish a model of human colon cancer metastatic to the liver of nude mice, to assess, in this setting, the therapeutic efficacy of radioimmunotherapy (RAIT) compared to standard chemotherapy and to evaluate, in a Phase I/II trial, the toxicity and therapeutic efficacy of RAIT in colorectal cancer patients with small volume disease metastatic to the liver. Multiple liver metastases of the human colon cancer cell line GW-39 were induced by intrasplenic injection of a 10% tumor cell suspension. Whereas controls were left untreated, therapy was initiated on day 10 or 20 after tumor inoculation with the 131I-labeled, low affinity anticarcinoembryonic antigen (anti-CEA) monoclonal antibody (MAb), F023C5 (Ka = 10(7) liters/mol), or the high-affinity anti-CEA MAb, MN-14 (Ka = 10(9) liters/mol), or chemotherapy (5-fluorouracil/leucovorin (folinic acid) versus irinotecan) at their respective maximum tolerated doses (MTDs). Twelve colorectal cancer patients with small volume disease metastatic to the liver (all lesions < or = 2.5 cm) were entered into a mCi/m2-based Phase I dose escalation study with 131I-labeled humanized version of MN-14, hMN-14. The patients were given single injections, starting at 50 mCi/m2 and escalating in 10-mCi/m2 increments. The MTD was defined as the dose level at which < or = 1 of 6 patients develop grade 4 myelotoxicity. In the mice, untreated controls died from rapidly progressing hepatic metastases at 6-8 weeks after tumor inoculation. The life span of mice treated with 5-fluorouracil/leucovorin was prolonged for only 1-3 weeks, whereas irinotecan led to a 5-8-week prolongation. In contrast, at their respective MTDs, the 131I-labeled low-affinity anti-CEA MAb, F023C5, led to a 20% permanent cure rate, and the high affinity MAb, MN-14, led to an 80% permanent cure rate, when therapy was initiated at 10 days after tumor inoculation. In the 20-day-old tumor stage, although it prolonged life, 131I-F023C5 was unable to achieve cures, whereas 131I-MN-14 was still successful in 20%. Histologically, no remaining viable tumor cells could be demonstrated in these animals surviving > 6 months. In patients, the MTD was reached at 60 mCi/m2 of hMN-14 (at 70 mCi/m2, two of three grade 4 myelotoxicities). Of 11 assessable patients, 2 had partial remissions (corresponding to an objective response rate of 18%), and 5 (45%) had minor/mixed responses or experienced stabilization of previously rapidly progressing disease. These data suggest that in small volume disease, RAIT may be superior to conventional chemotherapy. Antibodies of higher affinity seem to be clearly superior. The clinical response rates in patients with small volume disease are encouraging, being comparable to the response rates of conventional chemotherapeutic regimens but with fewer side effects. Ongoing studies will show whether treatment at the MTD will further improve therapeutic results.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
The outcome of clinical organ transplantations has improved considerably during the last decade, mainly due to the introduction and administration of new drugs for immunosuppression. Our knowledge of basic immune reactions has led to the development of a variety of new immunosuppressants that promise higher selectivity and additive or synergistic drug effects combined with less toxicity. This article gives a brief update of the immunosuppressive currently used in clinical organ transplantation.
Situs inversus is a rare anatomical abnormality that is often associated with multiple, complex malformations. In the past, patients with situs inversus were considered unsuitable candidates for transplantation or organ donation because associated visceral, and especially vascular, anomalies pose special technical difficulties. Recently, several cases of successful liver transplantation in recipients with situs inversus have been published using modified surgical techniques. This report reviews the literature and describes our own experience, including two liver graft recipients with complete and incomplete situs inversus, and one patient who underwent successful transplantation using a liver from a donor with situs inversus.
Treatment of ureteral stenosis has been attempted in many patients with transplanted kidneys. Treatment with the Acucise catheter system is a new approach for such patients. Published results of the approach in eight patients promise safety, effectiveness, and low perioperative morbidity. We report two cases of transplant ureteral stenosis treated with Acucise. One patient with stenosis of the pyeloureteral junction was treated successfully and has been free of recurrence for 9 months. The other patient had long-distance stenosis of the lower portion of the transplant ureter. Acucise incision was successful, but the patient had to undergo uretero-neocystostomy because of a ureteroperitoneal fistula. We use these cases to illustrate the disadvantages of endourological ureteral surgery as a standard therapeutic approach after renal transplantation. We suggest that Acucise is reliable when used in patients with uncomplicated short-distance ureteral stenosis; however, patients with long-distance stenosis or stenosis caused by heavily scarred periureteral tissue will not profit from it because of a higher complication rate.
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