A single center analysis of long-term outcomes and survival related risk factors in liver retransplantation.

Background: Liver retransplant is the only option to save a patient with liver graft failure. However, it is controversial due to its poor survival outcome compared to primary transplantation. Insufficient deceased organ donation in Taiwan leads to high waitlist mortality. Hence, living-donor grafts offer a valuable alternative for retransplantation. This study aims to analyze the single center's outcome in living donor liver retransplantation (re-LDLT) and deceased donor liver retransplantation (re-DDLT) as well as the survival related confounding risk factors. Methods: This is a single center retrospective study including 32 adults who underwent liver retransplantation (re-LT) from June 2002 to April 2020. The cohort was divided into a re-LDLT and a re-DDLT group and survival outcomes were analyzed. Patient outcomes over different periods, the effect of timing on survival, and multivariate analysis for risk factors were also demonstrated. Results: Of the 32 retransplantations, the re-LDLT group (n=11) received grafts from younger donors (31.3 vs. 43.75 years, P=0.016), with lower graft weights (688 vs. 1,457.2 g, P<0.001) and shorter cold ischemia time (CIT) (45 vs. 313 min, P<0.001). The 5-year survival was significantly better in the re-LDLT group than in the re-DDLT group (100% vs. 70.8%, P=0.02). This difference was adjusted when only retransplantation after 2010 was analyzed. Further analysis showed that the timing of retransplantation (early vs. late) did not affect patient survival. Multivariate analysis revealed that prolonged warm ischemia time (WIT) and intraoperative blood transfusion were related to poor long-term survival. Conclusions: Retransplantation with living donor graft demonstrated good long-term outcomes with acceptable complications to both recipient and donor. It may serve as a choice in areas lacking deceased donors. The timing of retransplantation did not affect the long-term survival. Further effort should be made to reduce WIT and massive blood transfusion as they contributed to poor survival after retransplantation.

Long-term outcomes of active vaccination against de novo hepatitis B among pediatric recipients of living donor liver transplantations with anti-HBc (+) grafts: a retrospective case-control study.

BACKGROUND: Active vaccination has been utilized to prevent de novo hepatitis B virus infection (DNHB) in anti-HBc (+) grafts after liver transplantation (LT). However, the long-term efficacy of active vaccination and graft/patient outcomes of anti-HBc (+) grafts have yet to be comprehensively investigated. MATERIALS AND METHODS: Among 204 pediatric patients enrolled in the study, 82 recipients received anti-HBc (+) grafts. For DNHB prevention, active vaccination was repeatedly administered prior to transplant. Anti-viral therapy was given to patients with pre-transplant anti-HBs<1000 IU/ ml (non-robust response) for 2 years and discontinued when post-transplant patients achieved anti-HBs>1000 IU/mL, while anti-viral therapy was not given in patients with an anti-HBs titer over 1000 IU/mL. The primary outcome was to investigate the long-term efficacy of active vaccination, while the secondary outcomes included the graft and patient survival rates. RESULTS: Among the 82 anti-HBc (+) transplant patients, 68% of recipients achieved a robust immune response, thus not requiring antiviral therapy. Two patients (2.4%) developed DNHB infection, one of which was due to an escape mutant. With a median follow-up of 150 months, the overall 10-year patient and graft survival rates were significantly worse in recipients of anti-HBc (+) grafts than those of anti-HBc (-) grafts (85.2% vs 93.4%, P=0.026; 85.1% vs 93.4%, P=0.034, respectively). Additionally, the 10-year patient and graft outcomes of the anti-HBc (+) graft recipients were significantly worse than those of the anti-HBc (-) graft recipients after excluding early mortality and non-graft mortality values (90.8% vs 96.6%, P=0.036; 93.0% vs 98.3%, P=0.011, respectively). CONCLUSION: Our long-term follow-up study demonstrates that active vaccination is a simple, cost-effective strategy against DNHB infection in anti-HBc (+) graft patients, whereby the need for life-long antiviral therapy is removed. Notably, both the anti-HBc (+) grafts and patients exhibited inferior long-term survival rates, although the exact mechanisms remain unclear.

PFDN4 as a Prognostic Marker Was Associated with Chemotherapy Resistance through CREBP1/AURKA Pathway in Triple-Negative Breast Cancer.

Breast cancer is the most common malignancy and its incidence is increasing. It is currently mainly treated by clinical chemotherapy, but chemoresistance remains poorly understood. Prefolded proteins 4 (PFDN4) are molecular chaperone complexes that bind to newly synthesized polypeptides and allow them to fold correctly to stabilize protein formation. This study aimed to investigate the role of PFDN4 in chemotherapy resistance in breast cancer. Our study found that PFDN4 was highly expressed in breast cancer compared to normal tissues and was statistically significantly associated with stage, nodal status, subclasses (luminal, HER2 positive and triple negative), triple-negative subtype and disease-specific survival by TCGA database analysis. CRISPR knockout of PFDN4 inhibited the growth of 89% of breast cancer cell lines, and the triple-negative cell line exhibited a stronger inhibitory effect than the non-triple-negative cell line. High PFDN4 expression was associated with poor overall survival in chemotherapy and resistance to doxorubicin and paclitaxel through the CREBP1/AURKA pathway in the triple-negative MDAMB231 cell line. This study provides insightful evidence for the value of PFDN4 in poor prognosis and chemotherapy resistance in breast cancer patients.

Vorinostat decrease M2 macrophage polarization through ARID1A6488delG/HDAC6/IL-10 signaling pathway in endometriosis-associated ovarian carcinoma.

Endometriosis is a common disease in women and may be one of the factors that induces malignant epithelial ovarian tumors. Previous studies suggested that endometriosis is related to ARID1A mutation mediating the expression of HDAC6, but the detailed pathogenic mechanism is still unclear. First, we collected endometriosis-associated ovarian carcinoma (EAOC) clinical samples and examined the expression of HDAC6. Our results found that the high HDAC6 expression group was positively correlated with EAOC histology (P = 0.015), stage (P < 0.000), and tumor size (P < 0.000) and inversely correlated with survival (P < 0.000). We also found that ARID1A6488delG/HDAC6 induced M2 polarization of macrophages through IL-10. In addition, the HDAC inhibitor (HDACi) vorinostat inhibited cell growth and blocked the effect of HDAC6. Tomographic microscopy was used to monitor the live cell morphology of these treated cells, and we found that vorinostat treatment resulted in substantial cell apoptosis by 3 h 42 min. Next, we established a transgenic mouse model of EAOC and found that vorinostat significantly reduced the size of ovarian tumors by inhibiting M2 macrophage polarization in mice. Together, these data demonstrate that the signaling pathway of E4F1/ARID1A6488delG/HDAC6/GATA3 mediates macrophage polarization and provides a novel immune cell-associated therapeutic strategy targeting IL-10 in EAOC.

Management of difficult hepatic artery reconstructions to reduce complications through continual technical refinements in living donor liver transplantations.

BACKGROUND: Hepatic artery reconstruction (HAR) for liver transplantation is crucial for successful outcomes. We evaluated transplantation outcome improvement through continual technical refinements. MATERIALS AND METHODS: HAR was performed in 1448 living donor liver transplants by a single plastic surgeon from 2008 to 2020. Difficult HARs were defined as graft or recipient hepatic artery ≤2 mm, size discrepancy (≥2 to 1), multiple hepatic arteries, suboptimal quality, intimal dissection of graft or recipient hepatic artery (HA), and immediate redo during transplantation. Technique refinements include early vessel injury recognition, precise HA dissection, the use of clips to ligate branches, an oblique cut for all HARs, a modified funneling method for size discrepancy, liberal use of an alternative artery to replace a pathologic HA, and reconstruction of a second HA for grafts with dual hepatic arteries in the graft. RESULTS: Difficult HARs were small HA (21.35%), size discrepancy (12.57%), multiple hepatic arteries (11.28%), suboptimal quality (31.1%), intimal dissection (20.5%), and immediate redo (5.18%). The overall hepatic artery thrombosis (HAT) rate was 3.04% in this series. The average HAT rate during the last 4 years (2017-2020) was 1.46% (6/408), which was significantly lower than the average HAT rate from 2008 to 2016 (39/1040, 3.8%) with a statistical significance (p = 0.025). Treatment for posttransplant HAT included anastomosis after trim back (9), reconstruction using alternatives (19), and nonsurgical treatment with urokinase (9). CONCLUSION: Careful examination of the HA under surgical microscope and selection of the appropriate recipient HA are key to successful reconstruction. Through continual technical refinements, we can reduce HA complications to the lowest degree.

Effects of Luteolin on Human Breast Cancer Using Gene Expression Array: Inferring Novel Genes.

Taraxacum officinale (dandelion) is often used in traditional Chinese medicine for the treatment of cancer; however, the downstream regulatory genes and signaling pathways mediating its effects on breast cancer remain unclear. The present study aimed to explore the effects of luteolin, the main biologically active compound of T. officinale, on gene expression profiles in MDA-MB-231 and MCF-7 breast cancer cells. The results revealed that luteolin effectively inhibited the proliferation and motility of the MDA-MB-231 and MCF-7 cells. The mRNA expression profiles were determined using gene expression array analysis and analyzed using a bioinformatics approach. A total of 41 differentially expressed genes (DEGs) were found in the luteolin-treated MDA-MB-231 and MCF-7 cells. A Gene Ontology analysis revealed that the DEGs, including AP2B1, APP, GPNMB and DLST, mainly functioned as oncogenes. The human protein atlas database also found that AP2B1, APP, GPNMB and DLST were highly expressed in breast cancer and that AP2B1 (cut-off value, 75%) was significantly associated with survival rate (p = 0.044). In addition, a Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the DEGs were involved in T-cell leukemia virus 1 infection and differentiation. On the whole, the findings of the present study provide a scientific basis that may be used to evaluate the potential benefits of luteolin in human breast cancer. Further studies are required, however, to fully elucidate the role of the related molecular pathways.

Metronomic vinorelbine is an excellent and safe treatment for advanced breast cancer: a retrospective, observational study.

Advanced breast cancer (ABC) has become a chronic disease. In such a situation, an effective therapy with low toxicities and economically acceptable is needed. Metronomic vinorelbine (mVNR) has been proved to be effective on the control of MBC. The aim of this study is to evaluate the efficacy and safety of mVNR as the salvage therapy for patients with ABC. Oral vinorelbine (VNR) was administered at 70 mg/m2, fractionated on days 1, 3, and 5, for 3 weeks on and 1 week off. Once the mVNR was combined with trastuzumab, or was combined with bevacizumab, the schedule was changed to 2 weeks on and 1 week off. Clinical data of patients with ABC who had received treatment with mVNR and tumor characteristics were collected and analyzed. From Mar. 2013 to Dec, 2020, there were 90 patients with ABC received mVNR. The overall response rate was 53.3% and overall disease control rate (DCR) was 78.9% in this study, including 4 (4.4%) cases reached complete response, 44 (48.9%) cases reached partial response and 23 (25.6%) cases were table disease. The median time to treatment failure (TTF) of the Lumina A patients was 13.3 months, Lumina B patients was 9.1 months, Her-2 enrich patients was 8.9 months, and triple negative breast cancer (TNBC) patients was 5.6 months. Median overall survival time for Lumina A, Lumina B, Her-2 enrich and TNBC were 54.6 months, 53.3 months, 59.5 months and 24.5 months separately. Side effects were minimal and manageable. Metronomic VNR can be an effective treatment for ABC either works as a switch maintenance or salvage therapy. In combination with target therapy or hormonal therapy, mVNR can further improve TTF and DCR with minimal toxicities. Further study should focus on the optimal dosage, schedule and combination regimen.

Can Microscopic Biliary Reconstruction Reduce Biliary Complication Rate in ABO-Incompatible Adult Living Donor Liver Transplantation?

BACKGROUND With the introduction of rituximab, ABO-incompatible (ABOi) living donor liver transplantation (LDLT) has been considered a feasible and safe procedure to overcome the shortage of organ donors. However, higher biliary complication rates remain an unresolved problem in the ABOi group. In our center, biliary anastomosis has been done with microscopic biliary reconstruction (MBR), which effectively reduced the biliary complication rate. The aim of the current study was to investigate whether the microscopic approach reduced anastomotic biliary complications in ABOi LDLT. MATERIAL AND METHODS From March 2006 to December 2018, 30 adult ABOi and 60 ABO-compatible (ABOc) LDLT patients were selected from over 1300 recipients through 1: 2 propensity score-matched cohorts. All patients received MBR during the transplantation. Biliary complications included bile leakage and biliary stricture. Patients with diffuse intrahepatic biliary stricture were excluded from analysis. RESULTS Patient characteristics were similar in the 2 groups. There was no in-hospital mortality in the ABOi LDLT. The long-term survival rates of the ABOi patients were comparable to those of the patients that underwent ABOc LDLT (87.1% vs 87.4%, P=0.964). Those in the ABOi group with anastomotic biliary complications were about 40%, which was higher than in the ABOc patients (40% vs 15%, P=0.01). CONCLUSIONS Microscopic biliary reconstruction does not help to reduce the high biliary complication rate in ABOi LDLT. Further investigation and identification regarding other risk factors and precautionary measures involving immunologic and adaptation mechanisms are needed.

Excellent Outcome in Living Donor Liver Transplantation: Treating Patients With Acute-on-Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF) is a fatal condition, and liver transplantation (LT) is a vital option for these patients. However, the result of living donor LT (LDLT) for ACLF is not well investigated. This study investigated the outcomes of LDLT in patients with ACLF compared with patients without ACLF. This was a single-center, retrospective, matched case-control study. From July 2002 to March 2017, a total of 112 patients with ACLF who underwent LDLT were enrolled according to the consensus of the Asian Pacific Association for the Study of the Liver. A total of 224 patients were selected for control comparison (non-ACLF) with demographic factors (sex, age, and body mass index) matched (1:2). Patients with ACLF were stratified into ACLF 1, 2, and 3 categories according to the number of organ failures based on the Chronic Liver Failure-Sequential Organ Failure Assessment score. Survival and surgical outcomes after LDLT were analyzed. The Model for End-Stage Liver Disease and Child-Turcotte-Pugh scores in the ACLF group were significantly higher than those in the non-ACLF group (P < 0.001). The 90-day, 3-year, and 5-year survival rates in the ACLF and non-ACLF groups were 97.3%, 95.5%, 92.9%, respectively, and 96.9%, 94.2%, and 91.1%, respectively (P = 0.58). There was more intraoperative blood loss in the ACLF group than in the non-ACLF group (P < 0.001). The other postoperative complications were not significantly different between the groups. A total of 20 patients (17.9%) in the ACLF group presented with 3 or more organ system dysfunctions (ACLF 3), and the 90-day, 3-year, and 5-year survival rates were comparable with those of ACLF 1 and ACLF 2 (P = 0.25). In carefully selected patients, LDLT gives excellent outcomes in patients with ACLF regardless of the number of organs involved. Comprehensive perioperative care and timely transplantation play crucial roles in saving the lives of patients with ACLF.

The efficacy and toxicity of adjuvant S-1 schedule with 2-week administration followed by 1-week rest in gastric cancer patients.

BACKGROUND: This study aimed to investigate the clinical outcome of adjuvant S-1 with 2-week administration followed by a 1-week rest for locally advanced gastric cancer (GC) patients. METHODS: The current study was a single retrospective cohort study that focused on the efficacy and toxicity of adjuvant S-1 with a 3-week schedule. A total of 60 patients who underwent total or subtotal gastrectomy plus D2 lymph node dissection and adjuvant S-1 treatment were identified. S-1 treatment began within 4 weeks after the operation; it was administered orally for 2 weeks, followed by a 1-week rest. The dose of S-1 was adjusted depending on adverse events (AEs), with at least 80 mg administered daily. The completion of 1-year S-1 was defined as S-1 continuation for 1 year with over 70% of the planned dose. Patients were followed up with for 5 years postoperatively and underwent hematologic tests and assessments of clinical symptoms every 3-6 weeks for 1 year after surgery. Computed tomography of the abdomen and panendoscopy were performed every 6 months during the first 2 years and at 1-year intervals thereafter until year 5 after surgery. RESULTS: The completion rate of 1-year adjuvant S-1 was 71.7%, and the 3-year disease-free survival and overall survival rates were 70.2% and 79.5%, respectively. Seventeen patients did not complete S-1 for 1 year, including 11 patients with tumor recurrence and 6 patients who developed intolerance. Most AEs of S-1 were grade 1-2, and the most frequent AEs (>20%) included anemia, fatigue, pigmentation, nausea, and diarrhea. The most common grade 3-4 AE was fatigue, which was observed in 6.7% of patients. Most patients tolerated the side effects. CONCLUSIONS: The results of our study confirm that the efficacy and safety of schedule modification of adjuvant S-1 treatment in patients with GC who underwent gastrectomy with D2 lymph node dissection are equal to those in a previous phase 3 study.

S1 versus Doublet Regimens as Adjuvant Chemotherapy in Patients with Advanced Gastric Cancer after Radical Surgery with D2 Dissection-A Propensity Score Matching Analysis.

BACKGROUND: Fluoropyrimidine- and platinum-based doublet regimen is the standard treatment of adjuvant chemotherapy (AC) for gastric cancer (GC). Our study aims to compare S1 with doublet regimens as AC in patients with advanced GC after radical surgery with D2 dissection. METHODS: Patients who were diagnosed with GC and underwent a curative surgery with D2 dissection followed by AC were enrolled into our study. A propensity score matching analysis was performed to reduce the selection bias. Kaplan-Meier curves were estimated for recurrence-free survival (RFS) and overall survival (OS). Cox regression models were conducted for survival. RESULTS: After propensity sore matching, 64 patients with S1 and 64 patients with doublet regimens were identified. The median RFS (p = 0.355) and OS (p = 0.309) were both insignificant between S1 and ST. Cox regression analysis demonstrated that pathologic stage and lymph node ratio (LNR) were independently correlated with survival. Patients were then stratified into low risk and high risk groups. The median RFS (p < 0.001) and OS (p < 0.001) had significant differences between low risk and high risk. In the high-risk group, doublet regimens were strongly associated with survival (p = 0.020) as compared with S1. While in the low-risk group, doublet regimen and S1 did not have statistically different survival benefits. CONCLUSIONS: Our study demonstrated that doublet regimens are superior to S1 in high-risk groups, and that survival outcomes are similar between doublet regimens and S1 in low-risk groups. Our prognostic model might have clinical implications for AC.

Bilateral proficiency over time leads to reduced donor morbidity in living donor hepatectomy.

BACKGROUND: Although left-lobe donation is considered safer, right-sided donor hepatectomy predominates in adult living donor liver transplantation (LDLT). We hypothesized that bilateral proficiency with donor hepatectomy reduces overall donor complications. METHODS: A retrospective review of 834 adult LDLT donors (221 left lobes) from January 2004 to December 2014 was performed, dividing cases into two eras based on left-graft experience. Donor complications within 6 months were investigated, focusing on graft side and surgical era. RESULTS: The overall complication rate was 17.6%, and was higher in right-lobe donors. In Era 2, during which left-lobe donation rates were three times higher, total complications decreased (14.7% vs. 20.9%, P=0.02). A significant reduction in postoperative ascites accounted for the lower overall complication rate. The proportion of major biliary complications (BCs) was halved from 62.5% to 25.0%. Right-lobe donor complications also decreased significantly (15.8% vs. 22.9%, P=0.032), demonstrating that it was not only increased left-lobe donations leading to lowered complication rates, but also greater experience with donor hepatectomy in general. CONCLUSIONS: Accumulating experience with bilateral donor hepatectomy leads to decreased donor morbidity and comparable outcomes for right and left lobes, further enhancing the goal of donor safety while balancing recipient needs.

What happened in 133 consecutive hepatic artery reconstruction in liver transplantation in 1 year?

BACKGROUND: The immediate challenges during microvascular reconstruction of hepatic artery (HAR) during liver transplantation (LT) can be many. Hence, in order to give a cross sectional view of these problems this study over a period of 1 year, showing our routine practice, was taken up. METHODS: From January 2015 to December 2015, a total of 133 LTs were performed in Kaohsiung Chang Gung Memorial Hospital, Taiwan. All hepatic artery (HA) reconstructions were performed by a microvascular surgeon under an operating microscope. RESULTS: In the 133 patients, one artery was anastomosed in 123 (92.5%) patients, two in 9 (6.8%) patients and three in 1 (0.7%) of the patient. Eleven (8.3%) arteries were less than 2 mm in size (1-1.9 mm). There were intimal dissections (IDs) involving either the donor or the recipient arteries of mild to severe nature in 9 (6.8%) patients. Immediately following graft arterial anastomosis, either there was no flow or an intraoperative hepatic artery thrombosis (HAT) was found in nine (7.1%-8 LDLT, 4.8%-1 DDLT) patients. Immediate re-do anastomosis was done in all of these patients who did well in the follow-up. The overall post-operative success rate was 99.2%. One patient (0.8%) developed postoperative HAT due to infection during follow up and died due to sepsis. CONCLUSIONS: Small vessels or HA injury are the frequently encountered problems by a micro vascular surgeon. The other problems could be ID, need to do multiple reconstructions, immediate HAT and ability to re-do the HAR immediately.

The surgical challenges of salvage living donor liver transplantation for Hepatocellular carcinoma; The cumulative experience of 100 cases - A retrospective cohort study and a propensity score analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) is increasingly managed by liver resection first then salvage liver transplantation in case of recurrence within accepted criteria. Many reports compared the safety of the salvage against the primary surgery in the setting of deceased donation but the difference in case of living donation is not sufficiently defined. Salvage living donor liver transplantation (SLDLT) is believed to be a more challenging surgery than primary living donor liver transplantation (PLDLT) due to operative field adhesions, in addition to the inherent difficulties particularly short vasculobiliary stumps. In this report, we compared both pathways from a surgical perspective in a homogenous LDLT-only cohort. MATERIALS AND METHODS: Over 15 years, 448 LDLTs for HCC were performed in a single liver transplant institution in Taiwan, including PLDLT (n = 348) and SLDLT (n = 100). A retrospective comparative review of the surgical outcomes of both pathways using a propensity score matching model (1-1, 100 pairs) was performed with adjustment for age, Child score and MELD score. The surgical outcome and survival were compared across 2 time eras. RESULTS: The operative data showed that SLDLT surgery encountered more extensive adhesions (57% vs. 0%, p < 0.001), longer operative duration (650 vs. 618 min, p=0.04), and was followed by more incidence of re-exploration (16% vs. 5%, p=0.01), than the PLDLT surgery. There was no significant difference regarding the incidence of in-hospital mortality, vascular and biliary complications, or overall survival (OS). The 1-year OS of SLDLT was inferior to PLDLT in the first 50 cases (90% vs. 98%, p=0.03), then the same OS was found in the 2nd 50 cases (96% vs. 96%, p=0.9). CONCLUSIONS: The SLDLT surgery is a demanding lengthy procedure with extensive adhesions and possibility of frequent re-explorations. Significant case load and high centre volume are important factors for safe practice of SLDLT and better cumulative OS.

Prediction of the Development of Persistent Massive Ascites After Living Donor Liver Transplantation Using a Perioperative Risk Score.

BACKGROUND: Persistent massive ascites (PMAS) longer than 14 days after living donor liver transplantation is not uncommon and associated with worse outcome. A predictive risk scoring system was constructed after analysis of recipient, graft, and surgery-related factors. METHODS: We retrospectively reviewed adult living donor liver transplantation recipients from 2005 to 2011 after excluding cases that experienced any intervention for perioperative vascular-related events. Two groups were identified, PMAS and non-PMAS. The score was constructed from significant factors using weighted odds ratios (OR). RESULTS: The study population included 439 recipients. Persistent massive ascites was evident in 74 cases (17%). Five significant risk predictors were identified in multivariate analysis: pretransplant serum creatinine greater than 1.5 mg/dL (OR, 5.693; weighted OR, 2), recipient spleen to graft volume ratio greater than 1.3 (OR, 4.466; weighted OR, 2), left lobe graft (OR, 3.196; weighted OR, 1), more than 1000 mL ascites at laparotomy (OR, 2.541; weighted OR, 1), and graft recipient weight ratio less than 0.8 (OR, 2.419; weighted OR, 1). The clinical scoring system was constructed and ranged from 0 to 7. Receiver operating characteristic analysis showed an area under the curve (0.778, P < 0.001). Internal validation of the score showed an area under the curve of 0.783. The 5- and 10-year survival rates for the non-PMAS versus the PMAS groups were 89% and 84% versus 81% and 48%, respectively (P = 0.001). CONCLUSIONS: The PMAS score is a predictive pretransplant clinical tool. A Clinical cutoff score of 4 might be decision-changing. Pretransplant correction of renal functions, deciding to harvest a large graft and/or consideration of splenic artery embolization could reduce the risk of PMAS.

P4 Stump Approach for Intraoperative Portal Vein Stenting in Pediatric Living Donor Liver Transplantation: An Innovative Technique for a Challenging Problem.

OBJECTIVE: The aim of this study was to evaluate the utility of the P4 stump stenting approach for treating portal vein (PV) complications in pediatric living donor liver transplantation (LDLT). BACKGROUND: PV complications cause significant morbidity and mortality in pediatric LDLT. Biliary atresia in the backdrop of pathological PV hypoplasia and sclerosis heightens the complexity of PV reconstruction. The authors developed a novel approach for intraoperative PV stenting via the graft segment 4 PV stump (P4 stump) to address this challenge. METHODS: From April 2009 to December 2016, 15 pediatric LDLT recipients (mean age 10.3 ±â€Š5.0 months, mean graft-recipient weight ratio 3.70%) underwent intraoperative stenting for suboptimal PV flow (<10 cm/s) or PV occlusion after collateral ligation and graft repositioning. Under portography, metallic stents were deployed via the reopened P4 stump of the left lateral segment grafts. RESULTS: PV diameter and peak flow increased significantly after stent placement (2.93 ±â€Š1.74 to 7.01 ±â€Š0.91 mm and 2.0 ±â€Š9.2 to 17.3 ±â€Š3.5 cm/s, respectively, P = 0.001 for both), and there were no technical failures. Stents in all surviving patients remained patent up to 8 years (mean 27.7 months), with no vascular or biliary complications. After implementation of the P4 approach, the incidence of variceal bleeding as a late complication decreased from 7% to zero. CONCLUSION: The P4 stump stenting approach affords procedural convenience, ease of manipulation, and consistent results with the potential for excellent long-term patency in children despite continued growth. This technique obviates the need for more demanding post-transplant stenting, and may become a substitute for complicated revision surgery, portosystemic shunting, or retransplantation.

Liver Transplantation for High Risk Hepatocellular Carcinoma After Liver Resection: A Sequential or Salvage Approach?

BACKGROUND Liver transplantation (LT) is the best radical treatment of hepatocellular carcinoma (HCC). Salvage liver transplantation (SalvLT) provides good outcomes for recurrent HCC cases after initial curative liver resection (LR). However, the salvage strategy is not feasible in all situations due to aggressive recurrences. Recently, sequential liver transplantation (SeqLT) was proposed for cases that show adverse pathological features after LR, thus LT is performed pre-emptively before recurrence. In this report, we compared the outcomes of SalvLT and SeqLT for surgical treatment of HCC. MATERIAL AND METHODS One hundred and ten cases underwent LR for HCC, then were subjected to either SalvLT (n=91) or SeqLT (n=19), from January 2001 to December 2015. For cases that underwent several LR before LT, we collected the data of the last LR before transplantation. A comparison was made according to pre- and post-transplant clinical and pathological variables. Survival analysis and comparison between both pathways are provided. RESULTS The median interval (months) between LR and LT for the SeqLT group and the SalvLT group were 9.6 and 22.2, respectively. (p=0.01). The LR histopathological features were similar in both groups. In the SalvLT group, the histopathological comparison between the criteria of last LR and the criteria of liver explants revealed that 14 cases advanced from stage I to stage II, one cases from stage I to stage IIIa, one case from stage I to stage IIIb, one case from stage I to stage IIIc, three cases from stage II to stage IIIb and one case from stage II to stage IIIc. The overall rate of pathological upstaging in the SalvLT group was 27%. The incidence of post-transplant HCC recurrence was 5% (1/19) and 11% (10/91) for the SeqLT and SalvLT groups, respectively (p=0.4). The incidence of post-LT in-hospital mortality was 0% among the SeqLT group and 2% (2/91) among the SalvLT group. The estimated rates of five-year overall survival and cancer specific survival for the SeqLT group versus the SalvLT group were (92.3% versus 87.6%; p=0.4) and (92.3% versus 91.9%; p=0.7), respectively. CONCLUSIONS The SeqLT approach might be associated with low incidence of cancer recurrence, better overall survival, and less operative mortality. Another possible benefit is the avoidance of aggressive non-transplantable HCC recurrences. More studies and/or randomization are required for highre evidence conclusions.

Expression and potential roles of sodium-potassium ATPase and E-cadherin in human gastric adenocarcinoma.

BACKGROUND: Gastric adenocarcinoma originates from an abnormal epithelium. The aim of this study was to investigate the expression of sodium-potassium ATPase (NKA), a transmembrane protein located in the epithelium for Na+ and K+ transportation, and E-cadherin, which are both crucial for the epithelium and adherens junction, as potential gastric cancer biomarkers. METHODS: 45 patients diagnosed with gastric adenocarcinoma were recruited. Immunohistochemistry and immunofluorescence were conducted to for localization of NKA α1-, ß1-isoform, and E-cadherin. NKA enzyme activity was determined by NADH-linked methods and immunoblotting of NKA α1-, ß1-isoform, and E-cadherin were performed to evaluate protein expression. RESULTS: Immunostaining revealed that NKA was co-localized with E-cadherin in the glands of the gastric epithelium. Both NKA activity and α1-isoform protein expression were reduced in the study group (P < 0.05), indicating impaired NKA functions. In the adherens junctions, the NKA ß1-isoform and E-cadherin were significantly reduced in the study groups (P < 0.05), indicating the adhesion force between cells may have been weakened. CONCLUSIONS: A significant decrease in NKA function (protein and activity) and E-cadherin in tumor lesions appear promising biomarker for gastric adenocarcinoma. Therefore, developing screening methods for detecting NKA function may be beneficial for the early diagnosis of gastric cancer. In our knowledge, this study was the first to investigate the NKA and E-cadherin expression in the relation of gastric adenocarcinoma in human patients.

Active immunization for prevention of De novo hepatitis B virus infection after adult living donor liver transplantation with a hepatitis B core antigen-positive graft.

De novo hepatitis B virus (DNHB) infections may occur in recipients who do not receive prophylaxis after liver transplantation (LT) with antibody to hepatitis B core antigen (anti-HBc)-positive donor grafts. Active immunization has been shown to prevent DNHB in pediatric recipients. Our aim is to investigate the efficacy of HBV vaccination for preventing DNHB in adult living donor liver transplantation (LDLT). In total, 71 adult antibody to hepatitis B surface antigen (anti-HBs)-negative LDLT patients who received anti-HBc+ grafts from 2000 to 2010 were enrolled into this study. Patients were given hepatitis B virus vaccinations with the aim of achieving anti-HBs > 1000 IU/L before transplant and >100 IU/L after transplant. The cohort was stratified into 3 groups: patients with pretransplant anti-HBs titer of > 1000 IU/L without the need for posttransplant prophylaxis (group 1, n = 24), patients with pretransplant low titer of <1000 IU/L who were given posttransplant lamivudine prophylaxis and responded appropriately to posttransplant vaccination by maintaining anti-HBs titers of > 100 IU/L (group 2, n = 30), and low titer nonresponders (anti-HBs titer of < 100 IU/L despite vaccination), for whom lamivudine was continued indefinitely (group 3, n = 17). All DNHB occurred in group 3 patients with posttransplant anti-HBs levels of < 100 IU/L, with an incidence rate of 17.6% compared with 0% in patients with posttransplant anti-HBs levels of > 100 IU/L (P = 0.001). A pretransplant anti-HBs level of >1000 IU/L was significantly associated with early attainment and a sustained level of posttransplant anti-HBs of >100 IU/L (P < 0.001). Active immunization is effective in preventing DNHB in adult LDLT if the posttransplant anti-HBs level is maintained above 100 IU/L with vaccination. Antiviral prophylaxis can be safely discontinued in patients who obtain this immunity. Liver Transplantation 23 1266-1272 2017 AASLD.