Michihiro Hayashi

Impact of graft size mismatching on graft prognosis in liver transplantation from living donors

BACKGROUND Although living donor liver transplantation for small pediatric patients is increasingly accepted, its expansion to older/larger patients is still in question because of the lack of sufficient information on the impact of graft size mismatching. METHODS A total of 276 cases of living donor liver transplantation, excluding ABO-incompatible, auxiliary, or secondary transplants, were reviewed from graft size matching. Forty-three cases were highly urgent cases receiving intensive care preoperatively. Cases were categorized into five groups by graft-to-recipient weight ratio (GRWR): extra-small-for-size (XS; GRWR<0.8%, 17 elective and 4 urgent cases), small (S; 0.8< or =GRWR< 1.0%, 21 and 7), medium (M; 1.0< or =GRWR<3.0%, 119 and 19), large (L; 3.0< or =GRWR<5.0%, 67 and 10), and extra-large (XL; GRWR> or =5.0%, 9 and 3). RESULTS Smaller-for-size grafts were associated not only with larger and older recipients, but also with rather older donors. Posttransplant bilirubin clearance was delayed and aspartate aminotransferase corrected by relative graft size was higher in XS and S. Posttransplant hemorrhage and intestinal perforation were more frequent in XS and S, and vascular complications and acute rejection were more frequent in larger-for-size grafts. Consequently, graft survival in XS (cumulative 58% and actuarial 42% at 1 year) and S (76% and 74%) was significantly lower compared with that in M (93% and 92%) in elective cases. Graft survival in L (83% and 82%) and XL (75% and 71%) did not reach statistical significance. CONCLUSIONS The use of small-for-size grafts (less than 1% of recipient body weight) leads to lower graft survival, probably through enhanced parenchymal cell injury and reduced metabolic and synthetic capacity. Although large-for-size grafts are associated with some anatomical and immunological disadvantages, the negative impact is less pronounced.

Right lobe graft in living donor liver transplantation.

BACKGROUND For the sake of donor safety in living donor liver transplantation (LDLT), the left lobe is currently being used most often for the graft. However, size mismatch has been a major obstacle for an expansion of the indication for LDLT to larger-size recipients, because a left lobe graft is not safe enough for them. METHODS In 1998, LDLT using a right lobe graft was introduced and performed on 26 recipients to overcome the small-for-size problem. The right lobe, which does not include the middle hepatic vein of the donor, was used. Initially, indication for right lobe LDLT was basically defined as an estimated left lobe graft volume/recipient body weight ratio (GRWR) of <0.8%, which was later raised to <1.0%. RESULTS All the donors recovered from the operation without persistent complications. Two donors with transient bile leakage were successfully treated with a conservative approach. A right lobectomy resulted in more blood loss (337+/-175 ml), and a longer operative time (6.67+/-0.85 hr) than a lateral segmentectomy, but not a left lobectomy. Grafts with a GRWR >0.8% were implanted in all recipients, except for two, who received relatively smaller right lobes (GRWR of 0.68% and 0.66%). In one of these two, the right lobe from the donor was used as the orthotopic auxiliary graft. Postoperative transitory increases in total bilirubin and aspartate transaminoferase for right lobe donors were higher than those for the left lateral segmentectomy. Nineteen recipients (73.1%) were successfully treated with this procedure. The causes of death were not specific for right lobe LDLT, except for one patient with a graft that had multiple hepatic venous orifices. These multiple and separate anastomoses of the hepatic veins caused an outflow block as a result of a positional shift of the graft, which finally led to graft loss. CONCLUSION Our experience suggests that right lobe grafting is a safe and effective procedure, resulting in the expansion of the indication for LDLT to large-size recipients. How to deal with the possible variation in the anatomy of the right lobe graft should be given attention throughout the procedure.

WEANING OF IMMUNOSUPPRESSION IN LIVING DONOR LIVER TRANSPLANT RECIPIENTS

Background. Some reported studies have indicated the possibility of immunosuppression withdrawal in cadaveric liver transplantation. The aim of this study was to evaluate the possibility and feasibility of weaning living donor liver transplant recipients from immunosuppression. Methods. From June of 1990 to October of 1999, 63 patients were considered to be weaned from immunosuppression. They consisted of 26 electively weaned patients and 37 either forcibly or incidentally weaned patients (nonelective weaning) due to various causes but mainly due to infection. Regarding elective weaning, we gradually reduced the frequency of tacrolimus administration for patients who survived more than 2 years after transplantation, maintained a good graft function, and had no rejection episodes in the preceding 12 months. The frequency of administration was reduced from the conventional b.i.d. until the start of weaning to q.d., 4 times a week, 3 times a week, twice a week, once a week, twice a month, once a month, and finally, the patients were completely weaned off with each weaning period lasting from 3 to 6 months. The reduction method of nonelective weaning depended on the clinical course of each individual case. When the patients were clinically diagnosed to develop rejection during weaning, then such patients were treated by a reintroduction of tacrolimus or an additional steroid bolus when indicated. Results. Twenty-four patients (38.1%) achieved a complete withdrawal of tacrolimus with a median drug-free period of 23.5 months (range, 3–69 months). Twenty-three patients (36.5%) are still being weaned at various stages. Sixteen patients (25.4%) encountered rejection while weaning at median period of 9.5 months (range, 1–63 months) from the start of weaning. All 16 were easily treated with the reintroduction of tacrolimus or additional steroid bolus therapy. Conclusions. We were able to achieve a complete withdrawal of immunosuppression in some selected patients. Although the mechanism of graft acceptance in these patients has yet to be elucidated, we believe that a majority of long-term patients undergoing living donor liver transplantation may, thus, be potential candidates to be successfully weaned from immunosuppression.

Biliary Anastomotic Complications in 400 Living Related Liver Transplantations

Abstract. The purpose of this study was to evaluate the cause and outcome of biliary anastomotic complications occurring after living related liver transplantation (LRLT). A database of 391 patients undergoing 400 LRLT from June 1990 to August 1998 was reviewed. The overall incidence of biliary anastomotic complications was 18.2% (71 patients). There were 45 bile leaks, 35 anastomotic strictures, and the bile duct was ligated inadvertently in 3 cases. Univariative analysis revealed that the manner of stent usage, intrapulmonary shunting, and gender of recipients were significant risk factors for leakage. Anastomotic leaks, cytomegalovirus infection, hepatic artery complications, and gender of recipients were significant risk factors for stricture. In pediatric patients older than 2 years old, ABO blood type compatibility was another risk factor for leakage and stricture. Choice of stent usage and earlier transplantation for patients with intrapulmonary shunting should reduce the rate of biliary leaks, and prophylaxis of leaks for patients with intrapulmonary shunting, and minimizing hepatic artery complications should reduce the rate of biliary stricture after LRLT. Avoidance of ABO-incompatible donors or innovative immunosuppression in ABO-incompatible transplantation should be considered in children.

Noninvasive evaluation of graft steatosis in living donor liver transplantation

Background. Hepatic steatosis affects graft function as well as postoperative recovery of donors in living donor liver transplantation. Liver macrovesicular steatosis in living donors was assessed using quantitative X-ray computed tomography (CT) analysis and histological examination of intraoperative liver biopsy. Methods. A total of 266 living donors with complete pretransplant CT data and intraoperative “time 0” biopsy were included in the study. Liver biopsy specimen obtained during donor operation was examined for macrovesicular steatosis and was classified as none; mild (<30%); moderate (30%–60%); or severe (>60%). Liver-to-spleen CT attenuation values ratio (L/S ratio) on noncontrast-CT was evaluated for its usefulness as an index of hepatic steatosis in comparison with other parameters including body mass index (BMI) and serum liver function tests (gamma-glutamyl transpeptidase, alanine aminotransferase, aspartate aminotransferase, cholinesterase, and total cholesterol) using receiver operating characteristic (ROC) analysis. Results. Histological grade of macrovesicular steatosis was none in 198 patients (74.4%), mild in 50 (18.8%), moderate in 15 (5.7%), and severe in 3 (1.1%). The median L/S ratios for the respective histological grades were 1.20 (range: 1.00–1.46), 1.12 (0.83–1.37), 1.01 (0.74–1.21), and 0.90 (0.70–0.99) (P<0.0001). The ROC curve for L/S ratio was located closest to the upper left corner, and the area under the curve of L/S ratio was significantly larger than that of any other preoperative variables. Conclusion. L/S ratio calculated from preoperative CT can be a useful tool to discriminate hepatic macrovesicular steatosis. Based on the present results, the optimal cut-off value for L/S ratio to exclude more than moderate steatosis would be 1.1.

Long-term outcome of living related liver transplantation for patients with intrapulmonary shunting and strategy for complications

BACKGROUND In 320 living related liver transplantation performed between June 1990 and September 1997, there were 21 living related liver transplantation for patients with intrapulmonary shunting, manifested by digital clubbing, cyanosis, and dyspnea. We report the long-term outcome for more 6 months and our strategy to overcome complications in these recipients. PATIENTS A total of 21 patients (age range 2-33 years, 19 children and 2 adults, 6 males and 15 females) were classified into three grades according to shunt ratio calculated by TcMAA pulmonary scintigraphy; 5 in mild group (shunt ratio: less than 20%), 6 in moderated group (20%-40%), and 10 in severe group (more than 40%). The original underlying liver disease was biliary atresia in all patients. RESULTS Spearmens correlation coefficient rank test revealed that shunt ratio correlated significantly with PaO2 in room air (P=0.0001), PaO2 in 100% oxygen (P=0.0004), hematocrit (P=0.0276), and period of dyspnea before transplantation (P=0.023). COMPLICATIONS Wound infection occurred in 80, 66, and 80%, and bile leakage in 20, 0, 40% in mild, moderate, and severe group, respectively. Patients who had portal vein thrombosis, and intracranial complication were classified as severe group and the incidence was 20 and 20%, respectively. The patient actuarial one year survival was 80, 66.7, and 48%, in mild, moderate, and severe group, respectively, although there was no significant difference. All patients who survived improved hepatopulmonary syndrome and the length of period required for the resolution was significantly correlated to the preoperative shunt ratio (P=0.023). COMMENTS Patients with severe shunting are susceptible to wound infection and bile leak. The trend of higher incidence of portal thrombosis and intracranial complications in the severe group was closely related high hematocrit. Secure surgical technique to reduce bile leak and delayed primary wound closure to reduce wound infection were found to be effective. Anticoagulant therapy by infusing heparin through the portal vein followed by coumadin could prevent fatal portal vein thrombosis without counter risk of fatal cerebral hemorrhage.

Auxiliary partial orthotopic living donor liver transplantation as an aid for small-for-size grafts in larger recipients.

BACKGROUND In countries where living donors are the only source of liver grafts, restrictions on graft size are a serious obstacle for the expansion of indications for adult recipients. To overcome this problem, auxiliary partial orthotopic liver transplants (APOLT*) was performed on the basis of the concept that the residual native liver would support the graft function until the graft had grown enough to function by itself. METHODS APOLT as an aid for small-for-size (SFS) grafts was reviewed retrospectively to evaluate its feasibility. Between April 1995 and March 1998, 20 recipients underwent APOLT, which was indicated because of a SFS graft in 15 of them. The indication was based on the estimated graft/recipients body weight ratio (GRWR). If the ratio was <0.8%, APOLT was performed. The other 5 patients had a graft with a GRWR >0.8% and underwent APOLT on the basis of the residual native liver supporting the graft function temporarily, 4 for supplementation of the defective enzyme in metabolic liver diseases and one for leaving the potential of the regeneration of the native liver in fulminant hepatic failure. The recipients who underwent APOLT because of a SFS graft were categorized as the SFS group, and the others were the second group. RESULTS In the SFS group, the age of the recipients ranged from 13 to 48 (median 23). The original indications of this group were fulminant hepatic failure in 2 recipients, acute deterioration of chronic liver diseases in 3, Wilsons disease in 2, biliary atresia in 4, primary biliary cirrhosis in 3, and primary sclerosing cholangitis (PSC) in one. The actual GRWR ranged from 0.45 to 0.72 (median 0.55). The graft was implanted after resection of the left lateral segment of the native liver. Except in the first two patients, the portal vein to the residual native liver was completely transected so that all of the portal blood drained into the graft liver. This procedure was successful in 9 patients. The cause of death in the other 6 was mainly infection. The mortality rate among the recipients with signs of advanced liver failure, such as massive ascites or hepatic coma, was higher, even though APOLT was used to support the SFS graft. In the second group, in the other five recipients who underwent APOLT for other indications, one recipient with fulminant hepatic failure died of sepsis caused by the dehiscence of bilio-enteric anastomosis. CONCLUSIONS APOLT as an aid for a SFS graft is technically viable. This procedure can thus expand the indication of living donor liver transplants for adult recipients when the native liver retains some functional capability to support the grafted liver during the immediate postoperative period.

Liver transplantation from non–heart beating donors in rats: Influence of viscosity and temperature of initial flushing solutions on graft function

BACKGROUND We evaluated the effect of warm (37 degrees C) versus cold (4 degrees C) solutions as the initial flush for liver preservation from non-heart beating donors in rats. METHODS An initial flush was performed just before donor hepatectomy with cold or warm University of Wisconsin solution (UW), UW without hydroxyethyl starch, sodium lactobionate sucrose solution, or lactated Ringers solution as the control group. A separate group also used as control received no initial flushing. Liver transplantation was performed, and the graft function was determined by survival and assessment of enzyme release. The viscosity of each solution and the vascular resistance of the graft were measured. RESULTS The 7-day survival rate was 83% and 100% in the warm and cold sodium lactobionate sucrose solution groups and 60% and 50% in the warm and cold lactated Ringers solution groups, respectively. In the no-initial-flush group, rats did not survive. The 7-day survival rate was 67% and 0% in the warm and cold UW groups, respectively. Eliminating the hydroxyethyl starch from the cold UW improved the survival to 67%. Serum alanine aminotransferase levels 1 day after transplantation in the no-initial-flush and the cold UW groups were significantly higher than those of the remaining groups. At 4 degrees C the viscosity was higher in the UW (86.2 cp) compared to hydroxyethyl starch-free UW solution (30.9 cp), lactated Ringers solution (24.5 cp), and sodium lactobionate sucrose solution (32.7 cp). The viscosity of UW at 37 degrees C was 34.7 cp. Vascular resistance correlated well with the viscosity. Livers flushed with solutions with a low viscosity showed lower vascular resistance than those flushed with cold UW and led to better survival. CONCLUSIONS These data suggest that the viscosity of the initial flushing solution may play an important role in determining the outcome of organ procurement from non-heart beating donors.

Impact of single-port cholecystectomy on postoperative pain.

This study compared postoperative pain following four‐port laparoscopic cholecystectomy (LC) and single‐port cholecystectomy (SPC).

The Effects Of Cold Preservation On Steatotic Graft Viability In Rat Liver Transplantation

Clinical experience suggests that grafts obtained from steatotic livers result in primary nonfunction more frequently than those from nonsteatotic livers. To date, however, only a few studies have been done to verify the accuracy of this observation. To investigate the effects of cold preservation on steatotic liver viability, liver grafts obtained from rats fed with a choline-deficient diet were transplanted after periods of cold preservation. Recipient survival rates with normal liver grafts were 8/8 (100%) and those with steatotic liver grafts were 7/8 (88%) (P>0.05) after 1-hr preservation with UW solution. After 9-hr preservation, however, these rates decreased significantly to 0/8 (0%) with steatotic grafts (P<0.01), but were not significantly decreased with normal grafts. LDH levels in the effluent at the time of transplantation were 133 IU/L (1-hr) and 512 IU/L (9-hr) in normal livers, but in steatotic livers these were elevated to 598 and 3141 IU/L, respectively (P<0.01). Recovery rates of hepatic blood flow measured by laser Doppler flowmeter after revascularization were 99% (1-hr) and 96% (9-hr) in normal grafts, but in steatotic grafts they were 98% (1-hr) and 63% (9-hr, P<0.01). In addition, the oxidative phosphorylation ability of liver mitochondria obtained from steatotic grafts was decreased significantly after cold preservation. The present results suggest that steatotic liver grafts are prone to lose their viability more easily than normal liver grafts after prolonged periods of cold preservation due to a combination of causes.