Learning curve of laparoscopic living donor right hepatectomy.

BACKGROUND: The feasibility and learning curve of laparoscopic living donor right hepatectomy was assessed. METHODS: Donors who underwent right hepatectomy performed by a single surgeon were reviewed. Comparisons between open and laparoscopy regarding operative outcomes, including number of bile duct openings in the graft, were performed using propensity score matching. RESULTS: From 2014 to 2018, 103 and 96 donors underwent laparoscopic and open living donor right hepatectomy respectively, of whom 64 donors from each group were matched. Mean(s.d.) duration of operation (252·2(41·9) versus 304·4(66·5) min; P < 0·001) and median duration of hospital stay (8 versus 10 days; P = 0·002) were shorter in the laparoscopy group. There was no difference in complication rates of donors (P = 0·298) or recipients (P = 0·394) between the two groups. Total time for laparoscopy decreased linearly (R2 = 0·407, ß = -0·914, P = 0·001), with the decrease starting after approximately 50 procedures when cases were divided into four quartiles (2nd versus 3rd quartile, P = 0·001; 3rd versus 4th quartile, P = 0·023). Although grafts with bile duct openings were more abundant in the laparoscopy group (P = 0·022), no difference was found in the last two quartiles (P = 0·207). CONCLUSION: Laparoscopic living donor right hepatectomy is feasible and an experience of approximately 50 cases may surpass the learning curve.

ANTECEDENTES: Se evaluó la viabilidad y la curva de aprendizaje de la hepatectomía derecha de donante vivo MÉTODOS: Se llevó a cabo una revisión de los donantes sometidos a hepatectomía derecha por un único cirujano. Las comparaciones entre el abordaje abierto y laparoscópico con respecto a los resultados operatorios, incluyendo el número of aberturas de los conductos biliares en el injerto se realizó utilizando un análisis de emparejamiento por puntaje de propensión. RESULTADOS: Desde 2014 a 2018, 96 y 103 donantes fueron sometidos a hepatectomía derecho de donante vivo por cirugía abierta y laparoscópica, respectivamente, de los cuales 64 donantes fueron emparejados para ambos grupos. La media del tiempo operatorio (304,3 ± 66,5 versus 252,2 ± 41,9 minutos, P < 0,001) y la mediana de la estancia hospitalaria fueron más cortas en el grupo de cirugía laparoscópica (10 versus 8 días, P = 0,002). No hubo diferencias entre ambos grupos en las tasas de complicaciones de los donantes (P = 0,298) o receptores (P = 0,394). El tiempo total de la laparoscopia disminuyó linealmente (R2= 0,407, ß = -0,914, P = 0,001) y esta disminución comenzó a partir aproximadamente de los 50 casos realizados cuando los casos fueron divididos en cuatro cuartiles (segundo a tercero y tercero a cuarto, P = 0,001 y P = 0,023, respectivamente). Aunque los injertos con aperturas de los conductos biliares fueron más numerosos en el grupo laparoscópico (P = 0,022), no se hallaron diferencias en los dos últimos cuartiles (P = 0,207). CONCLUSIÓN: La hepatectomía derecha de donante vivo por vía laparoscópica es viable, y una experiencia de aproximadamente 50 casos, puede superar la curva de aprendizaje.

Laparoscopic right posterior sectionectomy versus laparoscopic right hemihepatectomy for hepatocellular carcinoma in posterior segments: Propensity Score Matching Analysis.

BACKGROUND AND AIMS:: This study was designed to analyze the feasibility of laparoscopic right posterior sectionectomy compared to laparoscopic right hemihepatectomy in patients with hepatocellular carcinoma located in the posterior segments. MATERIAL AND METHODS:: The study included patients who underwent either laparoscopic right posterior sectionectomy or laparoscopic right hemihepatectomy for hepatocellular carcinoma located in segment 6 or 7 from January 2009 to December 2016 at Samsung Medical Center. After 1:1 propensity score matching, patient baseline characteristics and operative and postoperative outcomes were compared between the two groups. Disease-free survival and overall survival were compared using Kaplan-Meier log-rank test. RESULTS:: Among 61 patients with laparoscopic right posterior sectionectomy and 37 patients with laparoscopic right hemihepatectomy, 30 patients from each group were analyzed after propensity score matching. After matching, baseline characteristics of the two groups were similar including tumor size (3.4 ± 1.2 cm in laparoscopic right posterior sectionectomy vs 3.7 ± 2.1 cm in laparoscopic right hemihepatectomy, P = 0.483); differences were significant before matching (3.1 ± 1.3 cm in laparoscopic right posterior sectionectomy vs 4.3 ± 2.7 cm in laparoscopic right hemihepatectomy, P = 0.035). No significant differences were observed in operative and postoperative data except for free margin size (1.04 ± 0.71 cm in laparoscopic right posterior sectionectomy vs 2.95 ± 1.75 cm in laparoscopic right hemihepatectomy, P < 0.001). Disease-free survival (5-year survival: 38.0% in laparoscopic right posterior sectionectomy vs 47.0% in laparoscopic right hemihepatectomy, P = 0.510) and overall survival (5-year survival: 92.7% in laparoscopic right posterior sectionectomy vs 89.6% in laparoscopic right hemihepatectomy, P = 0.593) did not differ between the groups based on Kaplan-Meier log-rank test. CONCLUSION:: For hepatocellular carcinoma in the posterior segments, laparoscopic right posterior sectionectomy was feasible compared to laparoscopic right hemihepatectomy when performed by experienced laparoscopic surgeons.

Early Vs Late Liver Retransplantation: Different Characteristics and Prognostic Factors.

BACKGROUND: East Asia is a known endemic area for hepatitis B, and living donor liver transplantation is mainly performed. Liver retransplantation (ReLT) is expected to become an increasing problem because of a shortage of organs. This study aimed to compare early and late ReLT with consideration of specific circumstances and disease background of East Asians. METHODS: Between October 1996 and January 2015, 51 patients underwent ReLT; we performed a retrospective analysis of data obtained from medical records of the patients. Clinical characteristics, indication, causes of death, survival rate, and prognostic factors were investigated. RESULT: The survival rate for early ReLT (n = 18) was 51.5% and that for late ReLT (n = 33) was 50.1% at 1 year postoperatively. Continuous venovenous hemodialysis and the use of mechanical ventilators were more frequent, and pre-retransplant intensive care unit stay and prothrombin time was longer in early ReLT than in late ReLT. Operation time was longer and the amount of intraoperative blood loss was greater in late ReLT than in early ReLT. Multivariate analysis showed that a higher C-reactive protein level increased mortality in early ReLT (P = .045), whereas a higher total bilirubin level increased the risk of death in late ReLT (P = .03). CONCLUSION: Patients with early ReLT are likely to be sicker pre-retransplantation and require adequate treatment of the pretransplant infectious disease. On the other hand, late ReLT is likely to be technically more difficult and should be decided before the total bilirubin level increases substantially.

Comparison of Posttransplant Outcomes in Living Donor Liver Transplantation for Obese and Nonobese Recipients.

BACKGROUND: Although living donor liver transplantation for obese recipients has increased, it has not been determined that posttransplant outcomes in obese recipients are inferior compared with nonobese recipients. METHODS: From January 2001 to December 2016, there was a total of 58 (6%) obese patients (body mass index ≥30) in a cohort of 973 adult patients that underwent living donor liver transplantation. Propensity score matching and classification were performed based on the type of obesity, and there were 58 patients in the obese group and 141 patients in the nonobese group. We performed comparative analysis of posttransplant outcomes including Model for Early Allograft Function (MEAF) scoring and early allograft dysfunction (EAD). RESULTS: EAD was found in 11 (19%) and 31 (22%) patients in the obese and nonobese groups, respectively (P = .71). The obese group had a higher MEAF score than the nonobese group (5.2 vs 4.5, P = .007). The mean hospitalization of the obese group was shorter than in the nonobese group (32 vs 42 days, P = .003). Other posttransplant outcomes were similar between the obese and nonobese groups, including acute cellular rejection (8 vs 10 cases, P = .17), early graft failure (8 vs 12 cases, P = .30), index hospital mortality (6 vs 11 cases, P = .58), and comprehensive complication index (26.0 vs 24.6, P = .76). CONCLUSION: Posttransplant outcomes of the obese group were not inferior to the nonobese group. However, obesity can impact the severity of EAD and the incidence of early graft failure, based on significantly higher MEAF scores.

Long-term Outcomes for Liver Transplant Recipients in Terms of Hepatic Encephalopathy.

BACKGROUND: Liver transplantation (LT) is thought to resolve cognitive deficit due to hepatic encephalopathy (HE). The aim of this study was to determine the factors associated with the outcomes of patients with HE after LT. METHODS: The authors reviewed the medical records of 388 patients with HE who underwent LT from 1996 to 2014. RESULTS: There were 282 patients with grade 1-2 HE and 106 patients classified as grade 3-4. Patients in the latter group had a tendency for a more decompensated hepatic condition than patients with grade 1-2 HE. HE sequelae were only associated with grade 3-4 HE with borderline significance (P = .05). The cumulative 1-, 3-, and 5-year overall survival (OS) of patients with grade 1-2 HE were 81.9%, 77.3%, and 74.6%, whereas those of in patients with grade 3-4 HE were 77.4%, 73.3%, and 72.2%, respectively (P = .75). CONCLUSION: The sequelae of HE were only associated with the grade 3-4 HE. Aggressive treatment of HE prior to LT may prevent patients from deteriorating into high-grade HE, which could further contribute to improving the outcomes after LT.

Prognostic Factors Predicting Poor Outcome in Living-Donor Liver Transplantation for Fulminant Hepatic Failure.

BACKGROUND: Living-donor liver transplantation (LDLT) has been accepted as feasible treatment for fulminant hepatic failure (FHF), although it has generated several debatable issues. In this study, we investigated the prognostic factors predicting fatal outcome after LDLT for FHF. METHODS: From April 1999 to April 2011, 60 patients underwent LT for acute liver failure, including 42 patients for FHF at Samsung Medical Center, Seoul, Korea. Among 42 patients, 30 patients underwent LDLT for FHF, and the database of these patients was analyzed retrospectively to investigate the prognostic factors after LDLT for FHF. RESULTS: Among 30 patients, 7 patients (23%) died during the in-hospital period within 6 months, and 23 patients (77%) survived until recently. In univariate analyses, donor age (>35 years), graft volume (GV)/standard liver volume (SLV) (<50%), cold ischemic time (>120 minutes), hepatic encephalopathy (grade IV), hepato-renal syndrome (HRS), and history of ventilator care were associated with fatal outcome after LDLT for FHF. In multivariate analyses, HRS, GV/SLV (<50%), and donor age (>35 years) were significantly associated with fatal outcome. Although the statistical significance was not shown in this analysis (P = .059), hepatic encephalopathy grade IV also appears to be a risk factor predicting fatal outcome. CONCLUSIONS: The survival of patients with FHF undergoing LDLT was comparable to that in published data. In this study, HRS, GV/SLV <50%, and donor age >35 years are the independent poor prognostic factors.

Comparative Analysis of the Clinical Outcomes of Liver Transplantation for Probable and Definite Auto-immune Hepatitis by International Diagnostic Scoring Criteria.

BACKGROUND: Liver transplantation (LT) is an effective treatment for patients with end-stage liver disease caused by auto-immune hepatitis (AIH). However, diagnosis of AIH can be challenging for patients with end-stage liver disease at the time of transplantation. We classified patients into "probable" or "definite" AIH groups, using the diagnostic criteria of the International Autoimmune Hepatitis Group, and compared the clinical outcomes of AIH after LT in these 2 groups. METHODS: We performed a retrospective study of 18 patients who were diagnosed with AIH and underwent LT from March 2003 to March 2015 at a single institute. Of the 18 patients, 8 were diagnosed with definite AIH and 10 were diagnosed with probable AIH, according to the international scoring criteria. We evaluated the patient characteristics, recurrence rate, graft loss, and survival rates after LT. RESULTS: The mean follow-up duration was 59.3 months. Age, sex, medical condition at transplantation, warm ischemic time, cold ischemic time, and Model for End-Stage Liver Disease score did not differ significantly between the 2 groups. No patient died after LT in either group, but 1 patient in the definite AIH group had graft failure. In Kaplan-Meier analysis, the 5-year recurrence rates of the definite and probable groups were 14.3% and 0%, respectively (P = .992). CONCLUSIONS: The recurrence of definite AIH appeared to be higher than that of probable AIH. However, careful immunosuppressive therapy allowed the long-term survival of both definite and probable AIH patients after LT.

Use of Dexmedetomidine in Liver Transplant Recipients With Postoperative Agitated Delirium.

BACKGROUND AND OBJECTIVE: Agitated delirium has frequently occurred after liver transplantation in the intensive care unit (ICU) and sedative agents are used to treat patients. Recently, dexmedetomidine has been considered to be a promising agent for agitated delirium. METHODS: This study took place between January 2010 and October 2012 and 42 recipients were retrospectively enrolled. Sixteen recipients were enrolled in the dexmedetomidine group and 26 recipients were placed in the haloperidol group. To compare dexmedetomidine and haloperidol, the total ICU length of stay (ICU LOS), the ICU LOS after drug administration, and the supplemental doses of sedative agents used were assessed. The endpoint was discharge from the ICU. RESULTS: There were no significant drug-related complications in either group. Dexmedetomidine significantly decreased the ICU LOS and ICU LOS after the occurrence of delirium compared to haloperidol (13.7 days vs. 8.3 days, P = .039, 10.1 days vs. 3.1 days, P = .009). In the dexmedetomidine group, the dose of supplemental midazolam needed was lower than in the haloperidol group (1.5 mg vs. 6.85 mg, P < .001). CONCLUSION: Dexmedetomidine is a promising agent for the treatment of ICU-associated agitated delirium in liver transplantation recipients.

Role of Human Leukocyte Antigen Compatibility in Graft Outcomes After Living Donor Liver Transplantation.

PURPOSE: The influence of human leukocyte antigen (HLA) mismatch on liver transplantation has been widely studied, but is still controversial. The aim of this large single-center study was to analyze the role of HLA compatibility between donor and recipient in the graft outcomes of living donor liver transplantation (LDLT). MATERIALS AND METHODS: A total of 925 recipients who had undergone LDLT between March 2001 and April 2012 were retrospectively analyzed. HLA typing was performed using a standard complement-dependent cytotoxicity technique. The degree and type of HLA-A, HLA-B, and HLA-DR mismatch were assessed. We also investigated the posttransplantation laboratory data, incidence of rejection, recurrence of hepatitis B virus (HBV), and graft survival as outcome parameters. RESULTS: The type of HLA-A, HLA-B, and HLA-DR mismatch had no effect on rejection episodes, whereas the beneficial effect of a much lower degree (0-2) of HLA mismatch was notable. Recipients with 2 HLA-B mismatches or recipients with a higher degree of mismatch were associated with elevated bilirubin level, a higher recurrence rate of HBV, and inferior graft survival. A complete mismatch of 2 at the DR locus also decreased graft survival in LDLT recipients. CONCLUSIONS: This study confirmed that the degree of HLA mismatch, as well as the locus-specific type of HLA mismatch, namely B and DR, play a major role in graft outcomes after LDLT. To obtain an improved graft outcome, HLA compatibility should be considered in the setting of LDLT, which provides sufficient time to select a more favorable donor-recipient combination.

Case-matched comparison of ABO-incompatible and ABO-compatible living donor liver transplantation.

BACKGROUND: ABO-incompatible (ABO-I) living donor liver transplantation (LDLT) has a high success rate. There are few detailed comparisons regarding biliary complications, infective complications and patient survival between ABO-compatible (ABO-C) and ABO-I LDLT. The aim was to compare the outcomes of ABO-I LDLT with those of ABO-C LDLT using the matched-pairs method. METHODS: Patients who underwent ABO-I LDLT procedures between 2010 and 2013 were studied. They were matched for significant variables with patients who had ABO-C LDLT (1:2 matching). RESULTS: Forty-seven ABO-I LDLT procedures were included. Ninety-four patients who had ABO-C LDLT were selected as a comparator group. The incidence of cytomegalovirus, bacterial and fungal infections during the first 3 months was similar after ABO-I LDLT and ABO-C LDLT (85 versus 76 per cent, 28 versus 37 per cent, and 13 versus 20 per cent, respectively). Antibody-mediated rejection occurred after two procedures within 2 weeks of transplantation, but liver function improved with plasma exchange in both patients. There were no differences in the rate of acute rejection and biliary complications between ABO-I and ABO-C groups (P = 0.478 and P = 0.511 respectively). Three patients who had ABO-I LDLT developed diffuse intrahepatic biliary complications and progressed to graft failure. The 1-, 2- and 3-year patient survival rates after ABO-I LDLT and ABO-C LDLT were 89 versus 87 per cent, 85 versus 83 per cent, and 85 versus 79 per cent, respectively. CONCLUSION: The short-term outcomes of ABO-I LDLT were comparable to those of ABO-C LDLT in this study. ABO-I LDLT is an effective and safe transplant option with the potential to expand the pool of live donors.

Single-Center Experience of Consecutive 522 Cases of Hepatic Artery Anastomosis in Living-Donor Liver Transplantation.

OBJECTIVE: The aim of this study was to clarify risk factors and outcome of hepatic arterial complication after living-donor liver transplantations (LDLT). METHODS: From 2004 to 2010, 522 consecutive LDLTs were performed. We used univariate and multivariate analysis to identify the risk factor on a retrospective basis, and then analysis was performed for adult cases. Hepatic arterial complication included thrombosis, stenosis, and pseudoaneurysm. RESULTS: The arterial complication rate was 4.79% (25 cases). Each complication was 9 thromboses, 14 stenoses, and 2 pseudoaneurysms. Preoperative hemoglobin was significantly associated with thrombosis (P = .021), and arterial size with stenosis (P = .037). We could not find any association between arterial complications and biliary stricture. However, the outcome of biliary stricture treatment was associated with arterial stenosis. Of 9 cases with thrombosis, 7 patients underwent rearterialization and 2 were treated with low-molecular-weight heparin (LMWH). Of 14 stenosis cases, 2 patients were treated with the use of balloon dilatation, 10 patients were observed under LMWH, and 2 patients underwent retransplantation. In cases of pseudoaneurysm, 1 patient underwent revision of the aneurysm and the other was observed. CONCLUSIONS: In our cohort, preoperative low hemoglobin level was a risk factor for thrombosis and artery size a risk factor for stenosis.

Influence of hepatitis B virus reactivation on the recurrence of HBV-related hepatocellular carcinoma after curative resection in patients with low viral load.

It is unclear whether the reactivation of hepatitis B virus (HBV) influences the prognosis of hepatocellular carcinoma (HCC) after resection in patients with chronic hepatitis B. The aim of this study was to identify the influence of HBV reactivation on the recurrence of hepatitis B-related HCC after curative resection in patients with low viral load (HBV DNA <2000 IU/mL). We retrospectively analysed a total of 130 patients who underwent curative resection for HBV-related early stage HCC (single nodule; <5 cm/two or three nodules; <3 cm) with pre-operative HBV DNA levels <2000 IU/mL with serial HBV DNA tests. The predictive factors including HBV reactivation for the recurrence of HBV-related HCC after curative resection were investigated. Fifty-three patients (41%) had HBV reactivation after resection among 130 patients. HBV reactivation was observed in 22 of 53 patients with undetectable baseline HBV DNA and in 31 of 77 patients with detectable baseline HBV DNA. Cumulative recurrence rates after resection at 1, 2 and 3 years were 17.0%, 23.3% and 31.4%, respectively. The multivariable analysis demonstrated that the risk factors for the recurrence were the presence of microvascular invasion (hazard ratio (HR) 2.62, P = 0.003), multinodularity (HR 4.61, P = 0.005), HBV reactivation after resection (HR 2.03, P = 0.032) and HBeAg positivity (HR 2.06, P = 0.044). HBV reactivation after curative resection is associated with the recurrence of HBV-related HCC in patients with low viral load.

Serpin peptidase inhibitor clade A member 1 is a biomarker of poor prognosis in gastric cancer.

BACKGROUND: In a previous study, we reported that serpin peptidase inhibitor clade A member 1 (serpinA1) is upregulated in Snail-overexpressing gastric cancer. Although serpinA1 has been studied in several types of cancer, little is known about its roles and mechanisms of action. In this study, we examined the role of serpinA1 in the migration and invasion of gastric cancers and determined its underlying mechanism. METHODS: Expression levels were assessed by western blot analyses and real-time PCR. Snail binding to serpinA1 promoter was analysed by chromatin immunoprecipitation (ChIP) assays. The roles of serpinA1 were studied using cell invasion and migration assays. In addition, the clinicopathologic and prognostic significance of serpinA1 expression were validated in 400 gastric cancer patients using immunohistochemical analysis. RESULTS: Overexpression of Snail resulted in upregulation of serpinA1 in gastric cancer cell lines, AGS and MKN45, whereas knockdown of Snail inhibited serpinA1 expression. Chromatin immunoprecipitation analysis showed that overexpression of Snail increased Snail recruitment to the serpinA1 promoter. Overexpression of serpinA1 increased the migration and invasion of gastric cancer cells, whereas knockdown of serpinA1 decreased invasion and migration. Moreover, serpinA1 increased mRNA levels and release of metalloproteinase-8 in gastric cancer cells. Serpin peptidase inhibitor clade A member 1 was observed in the cytoplasm of tumour cells and the stroma by immunohistochemistry. Enhanced serpinA1 expression was significantly associated with increased tumour size, advanced T stage, perineural invasion, lymphovascular invasion, lymph node metastases, and shorter overall survival. CONCLUSIONS: Serpin peptidase inhibitor clade A member 1 induces the invasion and migration of gastric cancer cells and its expression is associated with the progression of gastric cancer. These results may provide a potential target to prevent invasion and metastasis in gastric cancer.

Expanded criteria for liver transplantation in patients with hepatocellular carcinoma.

Liver transplantation (LT) is one of the few effective treatment options for hepatocellular carcinoma (HCC). Our aim in this study was to evaluate the risk factors for HCC recurrence and propose new criteria for LT based on pretransplantation findings. One hundred eighty patients who underwent LT for HCC between 2002 and 2008 were reviewed retrospectively. Outcome measures included maximal tumor size and number of tumors revealed by radiological studies before transplantation, demographics, and tumor recurrence. Maximal tumor size >6 cm, >7 tumors, and alpha-fetoprotein (AFP) levels >1000 ng/mL were identified as independent prognostic factors of HCC recurrence in univariate and multivariate analysis. Disease-free survival rate in patients with a maximal tumor size ≤6 cm, ≤7 tumors, and/or AFP levels ≤1000 ng/mL at 1, 3, and 5 years was 97.9%, 91.5%, and 90.0%, respectively, but the 1-, 3-, and 5-year disease-free survival rate of patients who had a maximal tumor size >6 cm, >7 tumors, and/or AFP levels >1000 ng/mL was 61.9%, 47.6%, and 47.6%, respectively (P < .001). In conclusion, LT can improve the survival of patients with advanced HCC if they have a maximal tumor size ≤6 cm, tumor number ≤7, and/or AFP levels ≤1000 ng/mL.

Change of hepatitis B virus DNA and covalently closed circular DNA status in liver graft after liver transplantation.

Recurrence of hepatitis B virus (HBV) occurs despite prophylaxis, and covalently closed circular DNA (cccDNA) is thought to play a role owing to its resistance to prophylactic agents used. The aim of this study was to evaluate the changes of HBV DNA and cccDNA within the liver graft during liver transplantation (LT). Polymerase chain reaction (PCR) primers and probes were designed to measure total HBV DNA (tDNA) and cccDNA by real-time PCR. One hundred fifty samples from 70 patients who underwent LT for HBV were used for analysis. A 1st biopsy was taken from the donor before donor hepatectomy (Bx1), a 2nd from the recipient after reperfusion (Bx2), and a 3rd (Bx3) during follow-up after LT in 18 patients. Both tDNA and cccDNA after reperfusion were detected more frequently in pre-LT HBeAg(+) and high-HBV DNA titer recipients. However, the type and duration of antiviral agents and presence of mutation before LT did not influence the presence of tDNA or cccDNA in Bx2. tDNA positivity within the graft decreased from 41.4% to 22.2% during follow-up, but cccDNA did not (4.3% in Bx2 and 5.6% in Bx3). Although HBV recurrence was not related to pre-LT recipient HBeAg or HBV DNA titer, the presence of tDNA after reperfusion had strong correlation. The presence of tDNA within the graft is influenced by pre-LT viral replicative status, and although its presence decreases with prophylaxis, it is strongly correlated with recurrence. cccDNA does not have a role in predicting recurrence but is preserved within the graft despite prophylaxis.

Prediction of biliary complications after living-donor liver transplantation based on serum cytokine profile.

Biliary tract complications are the main concern associated with living-donor liver transplantation (LDLT). Many laboratory parameters have been studied for the early detection of post-LDLT complications, including various cytokines. To explore immunologic activation status and its clinical significance, the cytokine secretion patterns of LDLT patients who developed biliary complications were analyzed. Serum samples from LDLT recipients were collected 1 day before and 3, 7, 14, and 30 days after transplantation. Each sample was tested for interleukin (IL) 2, IL-4, IL-6, IL-8, IL-10, IL-12, interferon-α, and tumor necrosis factor α with the use of multiplex bead flow cytometry. Fifteen patients without any complications and 6 patients with biliary complications showed differential serum cytokine profiles. The biliary complication group (4 biliary stricture and 2 biliary obstruction patients) displayed significantly increased concentrations of IL-2 and IL-12 on post-transplantation days 3 and 7 and of IL-4 on post-transplantation day 7. Profiling cytokine secretion in the serum of patients in the first month of LDLT may be helpful for the prediction and diagnosis of biliary complications within 1 year.

PATHOME: an algorithm for accurately detecting differentially expressed subpathways.

The translation of high-throughput gene expression data into biologically meaningful information remains a bottleneck. We developed a novel computational algorithm, PATHOME, for detecting differentially expressed biological pathways. This algorithm employs straightforward statistical tests to evaluate the significance of differential expression patterns along subpathways. Applying it to gene expression data sets of gastric cancer (GC), we compared its performance with those of other leading programs. Based on a literature-driven reference set, PATHOME showed greater consistency in identifying known cancer-related pathways. For the WNT pathway uniquely identified by PATHOME, we validated its involvement in gastric carcinogenesis through experimental perturbation of both cell lines and animal models. We identified HNF4α-WNT5A regulation in the cross-talk between the AMPK metabolic pathway and the WNT signaling pathway, and further identified WNT5A as a potential therapeutic target for GC. We have demonstrated PATHOME to be a powerful tool, with improved sensitivity for identifying disease-related dysregulated pathways.

Implication of donor-recipient age gradient in the prognosis of graft outcome after deceased-donor kidney transplantation.

PURPOSE: Successful kidney transplantation leads to greater survival and improved quality of life for patients with end-stage renal disease. Among the most important influences on graft outcomes is donor age. We evaluated the relationships between the donor-recipient age gradient (DRAG) and the graft outcomes after deceased-donor kidney transplantation (DDKT). METHODS: From February 1995 to March 2011, a consecutive series of 526 adult DDKT recipients were analyzed. DRAG values were divided into two groups (negative versus positive years) and then four groups (≤-21, -20 to -1, 0 to 20, and ≥21 years). RESULTS: Median age of donors and recipients were 39 (range, 1-75) and 41 (range, 18-74) years, respectively. The degree of DRAG was not associated with episodes of allograft rejection. High or low DRAG had no effect on posttransplant serum creatinine levels or estimated glomerular filtration rates. However, negative levels of DRAG, particularly less than -20 years, were significantly correlated with superior 10-year death-censored graft survival (86.4% and 83.1% vs 72.2% vs 53.9%; overall P = .031), but not increased overall graft or patient survival. CONCLUSION: This study demonstrated that DRAG is a prognostic indicator of long-term graft outcomes after DDKT.

Can the kidney weight and recipient body weight ratio predict long-term graft outcome in living donor kidney transplantation?

We investigated the effect of the donor kidney weight (Kw) to recipient body weight (Rw) ratio (Kw/Rw) on long-term graft function. To investigate the impact of the Kw/Rw ratio on the graft function, we retrospectively collected data from 213 kidney transplant recipients at least 5 years Post-transplantations. Renal function showed a positive correlation with the Kw/Rw ratio until 5 years after transplantation (at 60 months after transplantation, R = 0.158, P = .023); however, this ratio does not affect graft survival (P = .794). We used the mixed-effect model to identify the factors that affect the estimated glomerular filtration rate (eGFR) over time. In univariate analysis, donor age, BSA, kidney weight, and Kw/Rw ratio were associated with eGFR. To identify independent factors that affect to the eGFR, multivariate analysis using a mixed model was applied. Donor age (P < .001) and Kw/Rw ratio (P < .001) were independent factors that affected the eGFR. To identify the cutoff values of the Kw/Rw ratio and donor age that affect long-term graft function, multiple testing using a mixed model was applied. The cutoff value for the Kw/Rw ratio was 3.16 (P = .0104) and the cutoff value of donor age was 44 years (P = .0001). Based on our results, we conclude that the Kw/Rw ratio and donor age are important factors for the long-term function of graft.