Toshimi Kaido

Impact of Sarcopenia on Survival in Patients Undergoing Living Donor Liver Transplantation

Skeletal muscle depletion, referred to as sarcopenia, predicts morbidity and mortality in patients undergoing digestive surgery. However, the impact on liver transplantation is unclear. The present study investigated the impact of sarcopenia on patients undergoing living donor liver transplantation (LDLT). Sarcopenia was assessed by a body composition analyzer in 124 adult patients undergoing LDLT between February 2008 and April 2012. The correlation of sarcopenia with other patient factors and the impact of sarcopenia on survival after LDLT were analyzed. The median ratio of preoperative skeletal muscle mass was 92% (range, 67–130%) of the standard mass. Preoperative skeletal muscle mass was significantly correlated with the branched‐chain amino acids to tyrosine ratio (r = −0.254, p = 0.005) and body cell mass (r = 0.636, p < 0.001). The overall survival rate in patients with low skeletal muscle mass was significantly lower than in patients with normal/high skeletal muscle mass (p < 0.001). Perioperative nutritional therapy significantly increased overall survival in patients with low skeletal muscle mass (p = 0.009). Multivariate analysis showed that low skeletal muscle mass was an independent risk factor for death after transplantation. In conclusion, sarcopenia was closely involved with posttransplant mortality in patients undergoing LDLT. Perioperative nutritional therapy significantly improved overall survival in patients with sarcopenia.

Portal pressure <15 mm Hg is a key for successful adult living donor liver transplantation utilizing smaller grafts than before

To prevent small‐for‐size syndrome in adult‐to‐adult living donor liver transplantation (A‐LDLT), larger grafts (ie, right lobe grafts) have been selected in many transplant centers. However, some centers are investigating the benefits of portal pressure modulation. Five hundred sixty‐six A‐LDLT procedures using right or left lobe grafts were performed between 1998 and 2008. In 2006, we introduced intentional portal pressure control, and we changed the graft selection criteria to include a graft/recipient weight ratio >0.7% instead of the original value of >0.8%. All recipients were divided into period I (1998‐2006, the era of unintentional portal pressure control; n = 432) and period II (2006‐2008, the era of intentional portal pressure control; n = 134). The selection of small‐for‐size grafts increased from 7.8% to 23.9%, and the selection of left lobe grafts increased from 4.9% to 32.1%. Despite the increase in the number of smaller grafts in period II, 1‐year patient survival was significantly improved (87.9% versus 76.2%). In 129 recipients in period II, portal pressure was monitored. Patients with a portal pressure <15 mm Hg demonstrated better 2‐year survival (n = 86, 93.0%) than patients with a portal pressure ≥15 mm Hg (n = 43, 66.3%). The recovery from hyperbilirubinemia and coagulopathy after transplantation was significantly better in patients with a portal pressure <15 mm Hg. In conclusion, our strategy for A‐LDLT has changed from larger graft–based A‐LDLT to controlled portal pressure–based A‐LDLT with smaller grafts. A portal pressure <15 mm Hg seems to be a key for successful A‐LDLT. Liver Transpl 16:718‐728, 2010.

Tissue factor expression in human colorectal carcinoma

It has been suggested that tissue factor (TF) plays an important role in tumor metastasis. Its expression in sarcoma cells was reported to up‐regulate the vascular endothelial growth factor (VEGF) gene and thereby enhance tumor angiogenesis, which is essential to tumor metastasis. Although many malignant tumors have been reported to express this protein constitutively, recent clinical studies have focused mainly on the correlations among TF expression, tumor progression, and histologic grade. Therefore, to address the role of TF and the underlying mechanism of hematogenous metastasis of colorectal carcinoma, the authors analyzed the correlations among TF expression, hepatic metastasis, and VEGF gene expression in surgical specimens. Furthermore, they analyzed the prognostic significance of TF expression with respect to overall patient survival.

Surgery-related morbidity in living donors for liver transplantation.

Introduction. Complications occur in a considerable proportion of living donors for liver transplantation. In this study, the surgery-related morbidity in living donors for more than 1000 liver transplantations was investigated. Methods. The donor morbidity between June 1990 and August 2007 was analyzed retrospectively and classified by the graft type and time period. The complication severity was graded using the Clavien scoring system. Results. During the study period, 1262 living donors underwent donor operations for liver transplantation. The donors were divided into two groups by the graft type: group RG (n=500), comprising right and extended right lobe grafts, and group LG (n=762), comprising non-right lobe grafts. The overall complication rate was significantly higher in group RG than that in group LG (44.2% vs. 18.8%, P<0.05). The complication severity was worse in group RG than in group LG. Although biliary complications were the most common complications in both the groups, the frequencies differed significantly (RG: 12.2% vs. LG: 4.9%; P<0.05). Short-term complications (within 4 weeks after the donor operation) occurred in 308 donors (24.4% of all donors). Complications after 4 weeks occurred in only 17 donors. Donor age, right lobe donation, and prolonged operation time were found to be independent risk factors for complications by multivariate analyses. Conclusions. Biliary complications were the most common and feared complications in living donors. There were more frequent and severe complications for right and extended right lobe donation than for non-right lobe donation. The possible risks of donor morbidity for different graft types should be understood and carefully considered.

Significance of des-gamma-carboxy prothrombin in selection criteria for living donor liver transplantation for hepatocellular carcinoma.

Des‐gamma‐carboxy prothrombin (DCP) levels reportedly correlate with histological features of hepatocellular carcinoma (HCC). We examined serum DCP as a predictor of HCC recurrence in 144 patients who underwent living donor liver transplantation. Receiver operating characteristics (ROC) analysis revealed superiority of DCP and AFP over preoperative tumor size or number for predicting recurrence. Multivariate analysis revealed tumor size >5 cm, ≥11 nodules, and DCP >400 mAU/mL as significant independent risk factors for recurrence. Incidence of microvascular invasion (62% vs. 27%, p = 0.0003) and poor differentiation (38% vs. 16%, p = 0.0087) were significantly higher for patients with DCP >400 mAU/mL than for patients with DCP ≤400 mAU/mL. In ROC analysis for patients with ≤10 nodules all ≤5 cm to predict recurrence, area under the curve was much higher for DCP than for AFP (0.84 vs. 0.69). Kyoto criteria were thus defined as ≤10 nodules all ≤5 cm, and DCP ≤400 mAU/mL. The 5‐year recurrence rate for 28 patients beyond‐Milan but within‐Kyoto criteria was as excellent as that for 78 patients within‐Milan criteria (3% vs. 7%). The preoperative DCP level offers additional information regarding histological features, and thus can greatly improve patient selection criteria when used with tumor bulk information.

Impact of quality as well as quantity of skeletal muscle on outcomes after liver transplantation

Intramuscular fat accumulation has come to be associated with loss of muscle strength and function, one of the components of sarcopenia. However, the impact of preoperative quality of skeletal muscle on outcomes after living donor liver transplantation (LDLT) is unclear. The present study evaluated the intramuscular adipose tissue content (IMAC) and psoas muscle mass index (PMI) in 200 adult patients undergoing LDLT at our institution between January 2008 and October 2013. Correlations of IMAC with other factors, overall survival rates in patients classified according to IMAC or PMI, and risk factors for poor survival after LDLT were analyzed. IMAC was significantly correlated with age (r = 0.229, P = 0.03) and PMI (r = −0.236, P = 0.02) in males and with age (r = 0.349, P < 0.001) and branched‐chain amino acid (BCAA)‐to‐tyrosine ratio (r = −0.250, P = 0.01) in females. The overall survival rates in patients with high IMAC or low PMI were significantly lower than those for patients with normal IMAC or PMI (P < 0.001, P < 0.001, respectively). Multivariate analysis showed that high IMAC [odds ratio (OR) = 3.898, 95% confidence interval (CI) = 2.025‐7.757, P < 0.001] and low PMI (OR = 3.635, 95% CI = 1.896‐7.174, P < 0.001) were independent risk factors for death after LDLT. In conclusion, high IMAC and low PMI were closely involved with posttransplant mortality. Preoperative quality and quantity of skeletal muscle could be incorporated into new selection criteria for LDLT. Perioperative nutritional therapy and rehabilitation could be important for good outcomes after LDLT. Liver Transpl 20:1413‐1419, 2014.

Posttransplant Bacteremia in Adult Living Donor Liver Transplant Recipients

Infectious complications such as bacteremia after living donor liver transplantation (LDLT) are associated with significant morbidity and mortality. We retrospectively analyzed the frequency and characteristics of posttransplant bacteremia in 181 adult LDLT recipients between April 2006 and November 2009, and we evaluated the risk factors for posttransplant bacteremia. One hundred seventeen episodes of bacteremia occurred in 62 of 181 recipients (34.3%) within 12 days (median) after transplantation (range = 1‐71 days). The most frequently isolated pathogens were Pseudomonasaeruginosa (26 episodes), methicillin‐resistant coagulase‐negative staphylococci (22 episodes), and Enterococcus sp. (11 episodes). The overall survival rate at 1 year for patients with bacteremia (n = 62) was significantly lower than the rate for patients without bacteremia (n = 119; 69.6% versus 92.3%, respectively, P < 0.0001). Multivariate analysis showed that Child‐Pugh class C (P = 0.0002), preoperative massive pleural effusion or ascites requiring drainage (P = 0.0384), postoperative cytomegalovirus infection (P = 0.0014), ABO incompatibility (P = 0.0188), and older donor age (P = 0.015) were independent risk factors for postoperative bacteremia. In conclusion, bacteremia occurred at a high rate after adult LDLT and induced a higher mortality rate in those who developed it. Infection control may play a pivotal role in improving early outcomes after LDLT. Liver Transpl 16:1379–1385, 2010.

Impact of preoperative quality as well as quantity of skeletal muscle on survival after resection of pancreatic cancer

BACKGROUND Skeletal muscle depletion, referred to as sarcopenia, is predictive of mortality in patients undergoing digestive operations. The impact of muscle quality on outcomes, however, is unclear. This retrospective study investigated the impact of preoperative skeletal muscle quantity and quality on survival in patients undergoing resection of pancreatic cancer. METHODS We investigated 230 patients who underwent resection of pancreatic cancer between 2004 and 2013. The quantity and quality of skeletal muscle, indicated by psoas muscle mass index (PMI) and intramuscular adipose tissue content (IMAC), were measured in preoperative computed tomography images. Overall survival (OS) and recurrence-free survival (RFS) rates were compared according to PMI and IMAC, and prognostic factors after pancreatic resection were assessed. RESULTS The OS and RFS rates in patients with low PMI were lesser than in those with normal/high PMI (P < .001, P < .001), with a mean survival time of 17.7 and 33.2 months, respectively. The OS and RFS rates in patients with high IMAC also were less than in those with normal/low IMAC (P < .001, P = .003) (mean survival time = 21.5 and 56.5 months, respectively). Low PMI (low muscle mass) and high IMAC (low muscle quality) were independent prognostic factors of poor OS (hazard ratio [HR] = 1.999, P < .001; HR = 2.527, P < .001) and RFS (HR = 1.607, P = .007; HR = 1.640, P = .004), respectively. CONCLUSION Preoperative sarcopenia, indicating low quality and quantity of skeletal muscle, is closely related to mortality after resection of pancreatic cancer.

Splenectomy does not offer immunological benefits in ABO-incompatible liver transplantation with a preoperative rituximab.

Background. Preformed anti-ABO antibodies are primarily responsible for antibody-mediated rejection (AMR) after ABO-incompatible (ABO-I) liver transplantation (LT) resulting in lethal hepatic necrosis and biliary complications. Splenectomy, an integral part of protocol for ABO-I LT, decreases anti-ABO antibodies. With the preoperative rituximab prophylaxis, role of the splenectomy for ABO-I LT is now under debate. We investigated the necessity of splenectomy by retrospective analyses of the short-term anti-ABO antibody response and long-term outcomes of ABO-I LT. Methods. Thirty-seven ABO-I LTs performed from May 2006 through July 2009, at Kyoto University Hospital, Kyoto, Japan, were retrospectively analyzed. Twenty-seven patients who underwent splenectomy (splenectomy group) received 329.6±35.8 mg rituximab 17.7±11.9 days before living donor LT. Ten patients without splenectomy (nonsplenectomy group) received 320.0±10.3 mg rituximab 26.6±21.3 days before transplantation. All patients received a posttransplant hepatic artery infusion with prostaglandin E1 and methylprednisolone. Perioperative anti-ABO immunoglobulin M and immunoglobulin G antibody titers, rejections, biliary complications, infections, and survival results were compared. Results. Preoperative rituximab with plasma exchange effectively reduced anti-ABO antibodies in both patient groups at the time of LT. There was no statistically significant difference observed in anti-ABO immunoglobulin M and immunoglobulin G antibody titers between the “splenectomy” and “nonsplenectomy” groups during the initial 8 weeks. The clinical outcomes, including AMR, biliary complications, infections, and survival, were similar in both the groups. Conclusions. Preoperative rituximab effectively decreased the anti-ABO antibodies sufficiently to prevent the AMR irrespective of splenectomy. Splenectomy does not offer any immunological benefit in ABO-I LT with preoperative rituximab.

Lower Limit of the Graft-to-Recipient Weight Ratio Can Be Safely Reduced to 0.6% in Adult-to-Adult Living Donor Liver Transplantation in Combination with Portal Pressure Control

INTRODUCTION The goal of this study was to examine whether the lower limit of the graft-to-recipient weight ratio (GRWR) can be safely reduced to make better use of a left-lobe graft in adult-to-adult living donor liver transplantation (LDLT) in combination with portal pressure control. PATIENTS AND METHODS Beginning in December 2007, our institution actively selected left-lobe grafts for use in liver transplantation seeking to minimize the risks to healthy donors. We gradually decreased the lower limit of the GRWR to preferentially select a left-lobe over a right-lobe graft: from ≥0.7% beginning in December 2007 to ≥0.6% beginning in April 2009. A portal pressure control program, targeting final portal pressures below 15 mm Hg, was also introduced to overcome small-for-size graft problems. The ratio of left-lobe grafts among all adult-to-adult LDLT grafts and the donor complication rate (defined as Clavien grade ≥ III, excluding wound infection) were compared between two time periods: June 1999 to November 2007 (period 1, n = 541) and December 2007 to February 2010 (period 2, n = 119). Overall survival rates were also compared between those recipients of a GRWR < 0.8% and those with a GRWR ≥ 0.8% in 198 recipients who underwent LDLT at our institution between April 2006 and February 2010. RESULTS Left-lobe grafts use increased from period 1 (65/541 recipients; 12.0%) to period 2 (50/119 recipients; 42.0%; P < .001). The donor complication rate tended to decrease from 13.8% in period 1 to 9.3% in period 2 (P = .115). The overall survival rate in 52 recipients with a GRWR < 0.8% did not differ from that in 146 recipients with a GRWR ≥ 0.8%. CONCLUSIONS The lower limit of the GRWR can be safely reduced to 0.6% in adult-to-adult LDLT in combination with portal pressure control.