Hisanao Chisuwa

Living related liver transplantation in adults.

OBJECTIVEnTo evaluate the outcome of living related liver transplantation (LRLT) in adult patients and to assess graft size disparity and graft regeneration.nnnSUMMARY BACKGROUND DATAnAlthough LRLT has been accepted as an optional life-saving procedure for pediatric patients with end-stage liver disease, the feasibility of LRLT for adult patients has not been reported with reference to a clinical series.nnnMETHODSnAdult-to-adult LRLT was performed using whole left lobar grafts in 13 patients (5 with primary biliary cirrhosis, 6 with familial amyloid polyneuropathy, 1 with biliary atresia, and 1 with citrullinemia). The 13 donors comprised 5 husbands, 3 sons, 2 sisters, 2 fathers, and 1 mother. The ratio of the graft volume to standard liver volume (GV/SV ratio) was calculated for use as a parameter of graft size disparity.nnnRESULTSnAlthough the liver graft was markedly small for size (GV/SV ratio 32%-59% at the time of LRLT), none of the 13 patients developed postoperative liver failure. Eleven of the patients are still alive and well with satisfactory graft function 2 to 35 months after LRLT. Graft liver volume increased rapidly after LRLT and approximated the standard liver volume with time.nnnCONCLUSIONSnOur LRLT program for adult patients has produced good results. LRLT in adults can be indicated for selected donor-recipient combinations.

Long-term results of living-related donor liver graft transplantation: a single-center analysis of 110 transplants.

BACKGROUNDnDifficulties of cadaveric donation and serious donor shortage have led to the development and popularization of living-related donor liver graft transplantation (LRLT). Because the history of this procedure is rather short, important aspects specific to this procedure have not been sufficiently documented. The objective of this study was to analyze a single centers 10-year experience with 110 LRLT in pediatric and adult patients with end-stage liver diseases.nnnMETHODSnThe medical records of 110 consecutive patients who underwent LRLT were reviewed. The recipients were comprised of 72 children and 38 adults. The graft volume corresponded to 26-192% of the recipients standard liver volume. The relationship between pretransplant covariates and patient and graft survival was analyzed. Actuarial patient/graft survival rates were determined at 1, 3, and 5 years. The type and incidence of posttransplant complications were analyzed, as was long-term graft function.nnnRESULTSnThe 1-, 3-, and 5-year actuarial patient and graft survival rates were 88%, 85%, and 85%, respectively. Log-rank test demonstrated that ABO-compatibility predicted patient survival rate, whereas patient age, underlying disease, patients clinical status, donor-recipient relation, donor age, and graft volume/standard liver volume ratio did not. Long-term liver function remains excellent. All the donors have returned to normal daily lives with an uneventful course.nnnCONCLUSIONSnLRLT is an efficacious procedure that provides excellent short-term and long-term survival. The indication criteria for both recipient and donor were legitimate in this series, except for transplant across ABO-incompatibility. Cautious expansion of this procedure may be justified under the situation of serious shortage of cadaveric donor.

Living liver donation: preoperative assessment, anatomic considerations, and long-term outcome1

Background. A major prerequisite for living donor liver transplantation (LDLT) as an acceptable treatment modality is thoughtful consideration of the donor. However, there has been no comprehensive audit of living liver donation focusing on issues such as donor selection, anatomic surveys, and long-term outcome. Methods. Between June 1990 and January 2002 at our institution, 160 LDLTs were performed and 177 patients were referred for LDLT. For these patients, a total of 203 potential donors were screened. The process of donor selection, safety of donor hepatectomy, and postoperative morbidity were investigated. Additionally, an anonymous questionnaire was administered to 100 donors who had undergone LDLT more than 3 years previously. Results. Thirty-eight (19%) of the 203 donor candidates were excluded. Precise estimation of the hepatic anatomy was indispensable for donor safety. None of the donors showed prolonged postoperative liver dysfunction nor developed complications requiring reoperation or readmission. There was no donor mortality. The responses to the questionnaire indicated that 95% of the living donors had not felt coerced to donate and that 5% were neutral about coercion pressure. There were no severe postoperative aftereffects, but minor problems were reported by 51% of the respondents. Conclusions. Our appraisal of the perioperative and long-term postoperative course of LDLT donors revealed that although most donors are satisfied after undergoing LDLT, there is a need for strict attention to the process of donor selection and long-term postoperative follow-up. The outcome of the present series seems to confirm the safety of donor hepatectomy.

Recent advance in living donor liver transplantation.

Living donor liver transplantation (LDLT)has been performed in more than 2000 cases around the world. This procedure is considered to have certain advantages over cadaveric liver transplantation, because detailed preoperative evaluation of the donor liver is possible and superior graft quality is available. The indication has recently been widened to include adult patients. The results of LDLT have been reported to be very good. In this article,several considerations on LDLT,including living donor selection and application to adult patients, are discussed. Between June 1990 and March 2001, 143 patients underwent LDLT at Shinshu University Hospital. During this period, 160 patients were determined to be candidates for liver transplantation in our institution, and 185 candidates were evaluated as potential donors for these patients. Thirty-eight of 185 donor candidates were excluded for reasons including liver dysfunction and withdrawal of consent. The recipients included 60 adults, 50 (83%) of whom are currently alive. Taking into account the worldwide shortage of cadaveric organ donation,the importance of LDLT will probably never diminish. This procedure should be established on the basis of profound consideration of donor safety as well as accumulated expertise of hepatobiliary surgery.

Fatal hemophagocytic syndrome after living-related liver transplantation: a report of two cases.

BACKGROUNDnHemophagocytic syndrome (HPS) is a serious hematological disorder caused by activated T lymphocytes in immunologically compromised patients. There is no report of HPS in liver transplant recipients.nnnMETHODSnAmong 135 patients who underwent living-related liver transplantation between June 1990 and October 2000, HPS developed in two pediatric patients (1.5%) on the 15th and 134th postoperative day, respectively. The courses of these patients were evaluated.nnnRESULTSnThe cause of HPS was unknown in patient 1 and suspected to be Epstein-Barr virus infection in patient 2. The course of patient 2 was also complicated by posttransplant lymphoproliferative disorder. Both patients had high fever, pancytopenia, coagulopathy, and marked elevation of serum-soluble interleukin 2 receptor, serum ferritin, and urine beta2-microglobulin levels. The diagnosis was established based on clinical findings, laboratory data, and bone marrow biopsy. Both patients died in an acute course despite intensive care.nnnCONCLUSIONSnHPS should be recognized as a severe hematological complication in liver transplant patients. Prompt institution of adequate treatment is necessary to prevent fatality.

Systemic reactive amyloidosis associated with Castleman's disease: serial changes of the concentrations of acute phase serum amyloid A and interleukin 6 in serum.

A case is reported of a 21 year old woman who suffered from Castlemans disease and systemic reactive amyloidosis. The serum concentrations of serum amyloid A (SAA) and interleukin 6 (IL-6) were extremely high and amyloid protein was immunohistochemically identified as AA. After surgical excision of a large retroperitoneal lymph node with the pathological findings of plasma cell type of Castlemans disease, both serum SAA and IL-6 declined, showing a similar pattern of reduction curves. All clinical symptoms and laboratory abnormalities greatly improved. The biochemical feature of Castlemans disease is abnormal production of IL-6 and this cytokine continuously may stimulate the synthesis of an amyloid precursor, SAA, causing systemic reactive (AA) amyloidosis. This pathogenetic theory is strongly supported by the present study.

Life-threatening veno-occlusive disease after living-related liver transplantation.

Veno-occlusive disease (VOD) can develop in association with the administration of cytotoxic chemotherapeutic agents and irradiation. In solid-organ transplant settings, azathioprine has been implicated as a predisposing factor. VOD with fatal outcome occurred in a post liver-transplant recipient who had never been exposed to any agents that have the potential to induce VOD. At onset, the disease manifested clinically as gross ascites and progressive jaundice and was observed after clinically diagnosed acute graft rejection. The disease was confirmed by histologic examinations. Histologic studies of biopsy samples from this patient revealed that most small hepatic veins less than 300 microm in diameter were affected, exhibiting concentric intimal thickening with sparse inflammatory cells. A few of the hepatic veins exhibited active endotheliitis with occasional extension of inflammation to neighboring centrilobular areas. Despite intensified immunosuppression, the observed fibrous obliterative changes were irreversible. Although the cause of VOD in this patient is tentative, the damage to the endothelium, associated with acute rejection, is likely to be attributable. VOD deserves recognition as one of the causes for liver dysfunction and persistent ascites after liver transplantation.

Esophageal intramural pseudodiverticulosis associated with esophageal perforation

Abstract: We report a rare case of esophageal intramural pseudodiverticulosis with lower esophageal stricture which perforated into the peritoneal cavity after the patient vomited. A 61-year-old man was admitted with severe chest and epigastric pain after dysphagia and vomiting. Under a diagnosis of upper gastrointestinal perforation, laparotomy was performed. The anterior wall of the abdominal esophagus was found to have ruptured, and proximal gastrectomy with abdominal esophagectomy was performed. His-tological examination revealed esophageal intramural pseudodiverticulosis with esophageal stricture distal to the site of rupture, and postoperative endoscopy showed diffuse pseudodiverticulosis in the remaining esophagus. The patient is free of symptoms 5 years after the surgery. This case suggests that careful treatment may be indicated in patients with esophageal intramural pseudodiverticulosis with stricture and elevated intraluminal pressure, to minimize the possibility of severe complications such as esophageal perforation.

RELATIONSHIP BETWEEN IN VIVO FK506 CLEARANCE AND IN VITRO 13-DEMETHYLATION ACTIVITY IN LIVING-RELATED LIVER TRANSPLANTATION

BACKGROUNDnAlthough it is important to maintain an appropriate blood concentration of FK506 after liver transplantation, significant interindividual variability in the actual FK506 dosage has been observed, presumably due to the wide variability of cytochrome P450 3A4 activity in liver microsomes.nnnMETHODSnA study was conducted in patients undergoing living-related liver transplantation and their donors to investigate the relationship between the in vitro FK506 demethylation activity in graft liver microsomes and the in vivo blood clearance of FK506. Liver biopsy tissue was obtained from 17 living donors to measure the in vitro formation rate of 13-demethyl derivative (M-I: the major metabolite of FK506). Erythromycin N-demethylation activity in vitro was also assessed in 11 cases. The FK506 blood clearance (CLss) was calculated from its constant infusion rate and steady-state blood concentration on day 4 after transplantation in 17 recipients.nnnRESULTSnThe FK506 infusion rate varied 4.6-fold from 8.3 to 38.4 ng/min/kg. The mean CLss of FK506 was 22.1+/-10.8 ml/min (10.1-45.2 ml/min). The M-I formation rate showed a wide variability, ranging from 0.098 to 0.571 nmol/min/mg protein. A significant correlation was observed between the in vitro estimated total metabolic ability of the graft for FK506 (M-I formation rate x graft weight) and the in vivo CLss of FK506 (r=0.770, P<0.001). Erythromycin N-demethylation (0.066-0.443 nmol/min/mg protein) showed a strong correlation with the M-I formation rate (r=0.891, P<0.01).nnnCONCLUSIONSnThe in vivo FK506 clearance can mainly reflect in vitro FK506 demethylation activity.

Efficacy of quantitative analysis of Epstein-Barr virus-infected peripheral blood lymphocytes by in situ hybridization of EBER1 after living-related liver transplantation : A case report

BACKGROUNDnWe describe a 1-year-old female who underwent living-related liver transplantation for biliary atresia and developed Epstein-Barr virus (EBV)-related posttransplant lymphoproliferative disorder. This disorder was resolved after withdrawal of immunosuppression therapy and administration of a high dose of acyclovir.nnnMETHODSnTo quantify the extent of EBV activation and EBV load in peripheral blood, we measured the levels of EBV-infected peripheral lymphocytes by in situ hybridization (ISH) of EBV-encoded small mRNA 1 (EBER1).nnnRESULTSnThe decline in the number of EBER1-positive lymphocytes (from 362/50,000 mononuclear cells to 0/50,000) after treatment was in accord with the patients clinical improvement.nnnCONCLUSIONSnThis finding showed that quantitative analysis of EBV-infected peripheral lymphocytes by ISH of EBER1 is very useful for monitoring the EBV load and response to treatment of patients with EBV-related disorders. Furthermore, ISH may become an important tool for the early diagnosis and prevention of life-threatening posttransplant lymphoproliferative disorder in posttransplant patients.