Graft-versus-host disease (GVHD) after liver transplantation is uncommon and the outcome is often fatal. A firm diagnosis of GVHD is difficult because the clinical triad of skin rash, marrow failure and diarrhoea can be indistinguishable from drug reaction or viral infection, and the presence of donor lymphocyte chimerism is not specific. We describe a case of severe GVHD in a female patient after liver transplantation from a male cadaveric donor. Skin biopsy showed characteristic changes of GVHD. Using Y-chromosome-specific fluorescent in situ hybridisation (FISH), male lymphocytes were demonstrated in 10% of marrow cells and in 90% of lymphocytes infiltrating the dermal epidermal junction. Donor human leucocyte antigens (HLAs) were detected in the peripheral blood, buccal mucosa and skin by polymerase chain reaction. The GVHD subsided with steroid and anti-thymocyte globulin, but recurred on tailing off of treatment. Despite maximum supportive therapy, including random donor leucocyte infusion, and marrow infusion from a HLA-identical sibling, the patient succumbed to sepsis. Our results showed the utility of combining morphological features with molecular techniques using FISH and HLA typing in confirming a diagnosis of GVHD.

Adult↗

PubMed2000

International sharing of split liver grafts in Asia: initial experience.

The donor shortage problem is particularly serious in Asia and has markedly limited progress in liver transplantation. The increasing demand has, in fact, made it necessary to resort to living donor liver transplantation in both pediatric and adult recipients. Nevertheless, expanding the use of split liver allografts is yet another option to increase the supply. This has a wide potential application on a regional level because most liver transplant programs are still small and may have limited resources in terms of being able to do two transplants in one sitting. The first experience of overseas sharing of split liver grafts in Asia took place in January 1999. The graft was from a 35-yr-old donor from Kaohsiung, Taiwan, who sustained irreversible brain damage in a vehicular accident and had optimal conditions for multiorgan donation. The liver was split ex vivo and the left lateral segment was given to a 3-yr-old girl with biliary atresia at the Chang Gung Memorial Hospital. The extended right lobe split graft was transported to Hong Kong and transplanted into a 51-yr-old male patient with end-stage hepatitis C cirrhosis who was then in a state of acute failure with hepatorenal syndrome. Graft function was excellent in both recipients and the patient from Taiwan was discharged without any complications. Unfortunately, the Hong Kong recipient developed a cerebrovascular accident and required a reoperation for bile leakage from the cut surface of the liver in the early postoperative period. He has made a steady recovery since then; graft function has remained good and his kidneys have recovered. Both patients are currently alive and well 11 months post-transplant. This initial experience of overseas sharing of split liver grafts in Asia demonstrates its feasibility. It has a potentially wide applicability and could lead to the establishment of a formal organ-sharing network in the region. Established competence and mutual trust among the participating liver transplant teams would be essential in perpetuating such a graft-multiplying strategy on an organized basis.

Adult↗

PubMed2000

Microsatellite analysis in post-transplantation lymphoproliferative disorder to determine donor/recipient origin.

Post-transplantation lymphoproliferative disorders (PTLD) are a group of heterogeneous diseases that occur after organ transplantation. Determination of the origin of the tumor cells not only provides clues to its possible pathogenetic mechanism, but also gives prognostic guidance in the clinical management of patients. We reviewed the clinicopathological features of four cases of PTLD that developed after solid organ transplantation. Using microsatellite analysis performed on paraffin-embedded tissue and using multiple, highly polymorphic markers, we have successfully determined the recipient/donor origin of the tumor cells in all of them. The time of onset of the PTLD ranged from 5 to 11 mo. All cases were diffuse large cell lymphomas of B-cell lineage, and the two cases that have been tested for EBV by in situ hybridization were positive. Three of the 4 PTLD were of donor origin and these three patients died of diseases unrelated to PTLD. The single patient with PTLD of recipient origin died of disseminated PTLD. The mean survival length of the three patients with donor origin was 26.3 mo, whereas that of the patient with recipient origin was 12 mo. Our results indicate a relatively high incidence of PTLD of donor origin among our patients with solid organ transplantation, as compared to other reported series. Moreover, the finding of the relatively indolent nature of PTLD of donor origin supports that determination of the donor/recipient origin of PTLD is of prognostic significance.

Adult↗

PubMed2000

Indications for liver transplantation in patients with chronic hepatitis B and C virus infection and hepatocellular carcinoma.

Patients with chronic hepatitis B virus (HBV) infection were not accepted for liver transplantation in Asia in the past because the hepatitis B immune globulin (HBIG) used to prevent post-transplantation recurrence was very expensive and it was generally believed that Asians with hepatitis B fared worse than Caucasians after liver transplantation. The availability of lamivudine has altered the indication of liver transplantation for these patients. Twenty-five Chinese patients with chronic HBV infection were given lamivudine as primary prophylaxis against HBV re-infection before transplantation. Five patients died within 40 days of transplantation. After a median follow-up period of 14 months (range, 5-39), 17 patients had lost serum HBsAg from 4 days to 27 months post transplantation, but it reappeared in three patients 4-12 months later. Antibody to HBsAg was detected periodically in the serum of 1 patients who had lost HBsAg. At the last follow-up, six patients were HBsAg-positive and HBV DNA was detected in only one of them. The indication for liver transplantation for chronic hepatitis C virus (HCV) infection is not as strict as for patients with chronic HBV infection because the long-term survival is similar to that of non-hepatitis C patients, even though re-infection by HCV in the recipients is nearly universal. The main issue in the selection of patients with HCV for liver transplantation is therefore identification of criteria that can predict re-infection and development of cirrhosis. These include factors such as multiple episodes of rejection, use of OKT3, pre-transplant viral load and genotype, but reports are not consistent and so there are no well-defined selection criteria. The selection criteria for patients with hepatocellular carcinoma are now well defined. Many studies have confirmed that a tumour > 5 cm, and showing vascular invasion, and poor differentiation adversely affects survival. In practice, only patients with a tumour < 5 cm and Child's C cirrhosis are accepted for liver transplantation. Transarterial oily chemoembolization and intralesional alcohol injection are used to control or down-stage the tumour while patients wait for a cadaveric liver graft.

Antiviral Agents↗

PubMed2000

Intracerebral hemorrhage after liver transplantation.

We report 5 patients with intracerebral hemorrhage after orthotopic liver transplantation (OLT) and identify the possible risk factors. Between November 1991 and April 1999, 75 adult patients received 77 orthotopic liver transplants at Queen Mary Hospital, Hong Kong. Five patients (6.5%) developed intracerebral hemorrhage postoperatively. Clinical and laboratory data were reviewed, and potential risk factors were analyzed. The 5 patients developed intracerebral hemorrhage within 40 days (range, 1 to 37 days; median, 4 days) after OLT. The mortality rate was 80% (4 of 5 patients). The intraoperative blood transfusion volume (median, 17,200 mL; range, 15,750 to 30,360 mL) administered to patients who developed intracerebral hemorrhage postoperatively was significantly greater than that (median, 6,990 mL; range, 1,840 to 22,680 mL) for patients without the complication (P =.0008). Massive intraoperative transfusion (>15,000 mL) was required in all 5 patients (100%) with intracerebral hemorrhage but only 9 of 72 patients (12.5%) in the other group (P =.0001). Four of 5 patients (80%) with intracerebral hemorrhage had intraoperative hypotension compared with 7 of 72 patients (9.7%) in the other group (P =.001). No significant difference was found in age, prothrombin time (PT), activated partial thromboplastin time (APTT), incidence of hypertension, bleeding at extracerebral sites, cyclosporine A neurotoxicity, thrombocytopenia, hemodialysis, and sepsis between the patients with and without intracerebral bleeding. However, the median cumulative score of coagulation parameters (PT, APTT, platelet count) was significantly greater in the group with than without intracerebral bleeding (median score, 3 v 1; P =.023). Intracerebral hemorrhage is 1 of the most disastrous complications after OLT. Intraoperative hypotension, massive intraoperative transfusion, and coagulopathy may be correlated with this complication.

Adult↗

PubMed2000

Value of intra-arterial calcium stimulated venous sampling for regionalization of pancreatic insulinomas.

BACKGROUND: Intra-arterial calcium stimulation with hepatic venous sampling (ASVS) for insulin gradients has been reported to be the most sensitive preoperative localizing technique for insulinomas. We reviewed our experience with ASVS to localize and guide the treatment of insulinomas over the past decade. METHODS: Eighteen patients who underwent ASVS before surgical exploration for insulinoma were studied. The accuracy of ASVS was compared with intraoperative findings and other localizing studies. RESULTS: There were no complications arising from the procedures. A more than 2-fold step-up in insulin level 30 to 60 seconds after injection to at least 1 feeding artery was observed in 16 patients. Fourteen of the 16 solitary tumors (87.5%) were correctly located; 100% (6/6 tumors) at the head and 80% (8/10 tumors) at the body/tail. The overall accuracy of this test was 89%, compared with 11%, 33%, 38%, and 63% of ultrasonography, computed tomography, magnetic resonance imaging, and endoscopic ultrasonography, respectively. Six enucleations and 10 distal resections were performed, which included 2 laparoscopic procedures. The combination of intraoperative ultrasonography with preoperative ASVS identified all tumors. CONCLUSIONS: ASVS is the most accurate preoperative localization tool for the localization of insulinomas and, in combination with intraoperative ultrasonography, can enhance surgical success.

Adult↗

PubMed2000

Technical refinement in adult-to-adult living donor liver transplantation using right lobe graft.

OBJECTIVE: To report the authors' experience with living donor liver transplantation in adults using right lobe liver grafts, performed by a modified technique. SUMMARY BACKGROUND DATA: The initial results of seven living donor liver transplants in adults using extended right lobe grafts were satisfactory, but serious complications occurred in two donors, and six recipients required repeat laparotomy. Another 11 similar operations were performed. Further evaluation was made with the aim of improving the postoperative outcome. METHODS: From December 1996 to August 1998, 11 patients underwent living donor liver transplantation using right lobe grafts. The first four patients underwent surgery using methods previously designed and the next seven underwent a modification designed to minimize devitalized tissues on the liver transection surface, improve hepatic venous drainage, and reduce the number of hepatic duct orifices. RESULTS: There were no donor deaths. Donor complications included cholestasis (n = 1) and minor wound infection (n = 1). All the first four recipients required a repeat laparotomy for infected necrotic liver transection surface (n = 1), acute pancreatitis (n = 1), hepatic vein thrombosis (n = 1), and leakage from one of the two bilioenteric anastomoses (n = 1). The patient with hepatic vein thrombosis died. In the last seven recipients, all of whom survived the operation, one required a repeat laparotomy with the discovery of a methicillin-resistant Staphylococcus aureus culture of fibrinous exudate at the left subphrenic peritoneum, and another had right hepatic duct stump necrosis. The latter was likely related to hypovolemic shock secondary to bleeding from the right saphenous vein on removal of a hemofiltration catheter. Comparison of the incidence of repeat laparotomy between the first four and the remaining seven recipients showed a significant trend of improvement. Combining the result of the seven patients reported previously, the improvement in terms of relaparotomy rate is significant. CONCLUSION: With modification of surgical technique, living donor liver transplantation in adults using right lobe liver grafts can become a relatively safe procedure.

Adolescent↗

PubMed2000

Significance of resection margin in hepatectomy for hepatocellular carcinoma: A critical reappraisal.

OBJECTIVE: To evaluate the influence of the width and histologic involvement of the resection margin on postoperative recurrence after resection of hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: The significance of the resection margin in hepatectomy for HCC remains controversial. A precise evaluation of the effects of the width and histologic involvement of the resection margin on postoperative recurrence is required to clarify the issue. METHODS: Two hundred eighty-eight patients with macroscopically complete resection of HCC were divided into groups with narrow (<1 cm) or wide (>/=1 cm) resection margins. The two groups were compared for postoperative recurrence rate and pattern of recurrence. A further analysis was performed to investigate the effects of histologic involvement of the resection margin on postoperative recurrence. RESULTS: Recurrence rates were similar between 150 patients with a narrow margin and 138 patients with a wide margin; the groups were comparable in other clinicopathologic variables. Most recurrent tumors occurred in the liver remnant at a segment distant from the resection margin or at multiple segments. Thirty-four patients had margin involved histologically by microscopic invasion from the main tumor (n = 13), venous tumor thrombi (n = 13), or microsatellites separate from the main tumor (n = 8). These patients had significantly higher recurrence rates than those with a histologically clear margin. However, a positive histologic margin was not a significant risk factor for recurrence by multivariate analysis. Tumor stage and perioperative transfusion were the only independent risk factors. CONCLUSIONS: The width of the resection margin did not influence the postoperative recurrence rates after hepatectomy for HCC. A positive histologic margin was associated with a higher incidence of postoperative recurrence, but in most patients this was related to the underlying venous invasion or microsatellites. Most intrahepatic recurrences were considered to arise from intrahepatic metastasis by means of venous dissemination, which a wide resection margin could not prevent.

Aged↗

PubMed2000

Risk factors, prevention, and management of postoperative recurrence after resection of hepatocellular carcinoma.

OBJECTIVE: To evaluate the current knowledge on the risk factors for recurrence, efficacy of adjuvant therapy in preventing recurrence, and the optimal management of recurrence after resection of hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: The long-term prognosis after resection of HCC remains unsatisfactory as a result of a high incidence of recurrence. Prevention and effective management of recurrence are the most important strategies to improve the long-term survival results. METHODS: A review of relevant English articles was undertaken based on a Medline search from January 1980 to July 1999. RESULTS: Pathologic factors indicative of tumor invasiveness such as venous invasion, presence of satellite nodules, large tumor size, and advanced pTNM stage, are the best-established risk factors for recurrence. Active hepatitis activity in the nontumorous liver and perioperative transfusion also appear to enhance recurrence. Recent molecular research has identified tumor biologic factors such as the proliferative and angiogenic activities of the tumor as new risk factors for recurrence. There is a lack of convincing evidence for the efficacy of neoadjuvant or adjuvant therapy in preventing recurrence. Retrospective studies suggested that postoperative hepatic arterial chemotherapy might improve disease-free survival, but results were conflicting. For the management of postoperative recurrence, studies have consistently indicated that surgical resection should be the treatment of choice for localized recurrence, be it in the liver remnant or extrahepatic organs. Transarterial chemoembolization and percutaneous ethanol injection are widely used to prolong survival in patients with unresectable intrahepatic recurrence, and combined therapy with these two modalities may offer additional benefit. CONCLUSIONS: Knowledge of the risk factors for postoperative recurrence provides a basis for logical approaches to prevention. Minimal surgical manipulation of tumors to prevent tumor cell dissemination, avoidance of perioperative blood transfusion, and suppression of chronic hepatitis activity in the liver remnant are strategies that may be useful in preventing recurrence. The efficacy of postoperative adjuvant regional chemotherapy deserves further evaluation. New concepts on the influence of tumor biologic factors such as angiogenic activity on recurrence of HCC suggest a potential role of novel approaches such as antiangiogenesis for adjuvant therapy in the future. Currently, the most realistic approach in prolonging survival after resection of HCC is early detection and aggressive management of recurrence. Randomized trials are needed to define the roles of various treatment modalities for recurrence and the benefit of multimodality therapy.

Antineoplastic Combined Chemotherapy Protocols↗