Efficacy and safety of sirolimus early conversion protocol in liver transplant patients with hepatocellular carcinoma: A single-arm, multicenter, prospective study.

Mammalian target of rapamycin (mTOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant (LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival (RFS) in hepatocellular carcinoma (HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specific for the first 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefits for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data. Trial register: Trial registered at http://www.chictr.org.cn: ChiCTR2100042869.

The expression profiles of circRNAs in lung tissues from rats with lipopolysaccharide-induced acute respiratory distress syndrome: A microarray study.

The development of circular RNA (circRNA) microarray has facilitated the study of the role of circRNAs in regulating gene expression through a circRNA-miRNA-mRNA network. In our study, microarray was performed to detect the expression profiles of circRNAs during lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS). Twenty rats were randomly divided into 2 groups, the control group and the LPS group, 10 rats in each group. Three rats each from both groups were randomly selected. Using circRNA microarray data, we compared the circRNA expression profiles in lung tissues between these 6 rats. The most differentially expressed circRNA species from these profiles were validated and optimized as ARDS biomarkers and potential therapeutic targets. Overall, 395 and 562 circRNAs were significantly up- and down-regulated in LPS group vs. control group, respectively. Six up-regulated and 4 down-regulated circRNAs from the top 10 candidates were eventually selected to be validated. Among them, only 4 up-regulated circRNAs (mmu_circRNA_19423, rno_circRNA_010489, rno_circRNA_011426, mmu_circRNA_30664) and 1 down-regulated circRNA (rno_circRNA_005564) exhibited significant validation. The 5 highest ranking target miRNAs of these 5 validated circRNAs were predicted according to the miRNA support vector regression method. This is the first study to investigate circRNA expression profile and a large number of aberrantly expressed circRNAs were revealed during ARDS. The significantly over- or under-expressed circRNA may represent a novel biomarker and be developed as a novel therapeutic target for the clinical management of ARDS. The results are preliminary and need to be confirmed in further well-designed studies with larger sample size.

Autophagy inhibitor 3-methyladenine alleviates overload-exercise-induced cardiac injury in rats.

Overload-exercise (OE) causes myocardial injury through inducing autophagy and apoptosis. In this study we examined whether an autophagy inhibitor 3-methyladenine (3-MA) could alleviate OE-induced cardiac injury. Rats were injected with 3-MA (15 mg/kg, iv) or saline before subjected to various intensities of OE, including no swim (control), 2 h swim (mild-intensity exercise, MIE), 2 h swim with 2.5% body weight overload (moderate OE; MOE), 5% overload (intensive OE; IOE) or 2.5% overload until exhausted (exhaustive OE; EOE). After OE, the hearts were harvested for morphological and biochemiacal analysis. The cardiac morphology, autophagosomes and apoptosis were examined with H&E staining, transmission electron microscopy and TUNEL analysis, respectively. Autophagy-related proteins to (LC3-II/I and Beclin-1) and apoptosis-related proteins (Bcl-2/Bax) were assessed using Western blotting. Our results showed that compared with the control, MIE did not change the morphological structures of the heart tissues that exhibited intact myocardial fibers and neatly arranged cardiomyocytes. However, IOE resulted in irregular arrangement of cardiomyocytes and significantly increased width of cardiomyocytes, whereas EOE caused more swollen and even disrupted cardiomyocytes. In parallel with the increased OE intensity (MOE, IOE, EOE), cardiomyocyte autophagy and apoptosis became more and more prominent, evidenced by the increasing number of autophagosomes and expression levels of LC3-II/I and Beclin-1 as well as the increasing apoptotic cells and decreasing Bcl-2/Bax ratio. 3-MA administration significantly attenuated OE-induced morphological changes of cardiomyocytes as well as all the autophagy- and apoptosis-related abnormalities in MOE, IOE and EOE rats. Thus, the autophagy inhibitor 3-MA could alleviate OE-induced heart injury in rats.

Mild hypothermia pretreatment protects hepatocytes against ischemia reperfusion injury via down-regulating miR-122 and IGF-1R/AKT pathway.

BACKGROUND: Mild hypothermia has been well known as an effective way to reduce ischemia reperfusion injury (IRI), while the mechanisms are still unclear. More and more evidences have indicated that miRNAs should been involved in the regulation of IRI and expecially some miRNAs have shown temp-responsiveness for temperature variation. Therefore, the role of miR-122 in mild hypothermia pretreatment after IRI was investigated. METHODS: We established a LO2 cell anoxia-reoxygenation injury model to simulate liver IRI. Five groups of differently pretreated L02 cells were studied. ALT, AST and LDH as well as cell viability were measured. Flow cytometric analysis was used to evaluate the apoptosis. The expression of miR-122 was quantified by qRT-PCR. Insulin-like growth factor 1 receptor (IGF-1R), protein kinase B (p-AKT), AKT, forkhead box O3a (p-FOXO3a) and Caspase3 were examined using western blot analysis. RESULTS: We found that mild hypothermia pretreatment could reduce the hepatocellular injury and induce a significant down-regulation in miR-122 expression after IRI. However, those effects of protection were attenuated by overexpressed miR-122 blockade. We further demonstrated that down-regulation of miR-122 promoted IGF-1R translation and AKT activity, suppressed FOXO3a activity and Caspase3 expression after mild hypothermia pretreatment, which was abrogated by miR-122 mimic. CONCLUSION: Our data clearly demonstrate that mild hypothermia pretreatment can down-regulate miR-122 to protect hepatocytes against IRI through activation IGF-1R/AKT signaling pathway and inhibit cells apoptosis.

Fucoidan reduces inflammatory response in a rat model of hepatic ischemia-reperfusion injury.

Ischemia-reperfusion (I/R) injury after a liver transplant is a major cause of severe complications that lead to graft dysfunction. Fucoidan, a complex of sulfated polysaccharides derived from marine brown algae, demonstrated antiapoptotic as well as potential anti-inflammatory properties in previous studies. Fucoidan has also shown protective effects on I/R-injured kidney and heart. However, whether fucoidan can attenuate hepatic I/R injury has not been examined. To clarify the role of fucoidan in hepatic I/R injury, Sprague-Dawley rats were subjected to sham operation or ischemia followed by reperfusion with treatment of saline or fucoidan (50, 100, or 200 mg·(kg body mass)(-1)·d(-1)). The fucoidan-treated group showed decreased levels of alanine aminotransferase and aspartate aminotransferase compared with the control group. Myeloperoxidase and malondialdehyde activities and mRNA levels of CD11b in the fucoidan-treated group were significantly decreased. Hepatocellular swelling/necrosis, sinusoidal/vascular congestion, and inflammatory cell infiltration were also attenuated in the fucoidan group. The expression of TNF-α, IL-6, IL-1ß, CXCL-10, VCAM-1, and ICAM-1 were markedly decreased in the samples from the fucoidan-treated group. Fucoidan largely prevented activation of the inflammatory signaling pathway, compared with the control group. In summary, fucoidan can protect the liver from I/R injury through suppressing activation of the inflammatory signaling pathway, as well as the expression of inflammatory mediators, and inflammatory cell infiltration.

Donor-Derived Transmission of Scedosporiosis in Kidney Transplant Recipients from a Systemic lupus erythematosus donor.

Donor-derived infection (DDI) associated with Scedosporium spp is extremely rare, and results in a very poor prognosis. The present study reports a probable DDI due to Scedosporium boydii (S. boydii) from a donor with neuropsychiatric systemic lupus erythematosus. Two recipients developed Scedosporiosis after kidney transplantation from the same donor. Recipient 1 died of central nervous system infection due to S. boydii based on the clinical presentations, and the positive metagenomic next-generation sequencing (mNGS) and culture results for the cerebrospinal fluid. The other recipient with urinary tract obstruction due to S. boydii, which was identified through the positive culture and mNGS results of the removed stents, was successfully treated by stent replacement and voriconazole administration. Undiagnosed disseminated donor infection and the transmission of S. boydii should be given attention, particularly when the donor and recipients have primary immunodeficiency disease. The screening of donors and recipients for S. boydii using mNGS may be helpful in guiding antifungal prophylaxis and treatment recipients, due to its higher sensitivity and shorter diagnostic time relative to other traditional techniques.

Effect of neoadjuvant cetuximab, capecitabine, and radiotherapy for locally advanced rectal cancer: results of a phase II study.

PURPOSE: The aim of this study was to investigate the efficacy and safety of neoadjuvant cetuximab, capecitabine, and radiotherapy for patients with locally advanced rectal cancer. METHODS: Sixty-three eligible patients were selectively enrolled in this study. Neoadjuvant treatment consisted of cetuximab and capecitabine for 6 weeks and radiotherapy for 5 weeks. Surgical resection was performed 6-8 weeks after the completion of neoadjuvant treatment. KRAS mutation statuses were analyzed retrospectively after the cetuximab treatment. All the patients underwent a standardized postoperative follow-up for at least 3 years. RESULTS: A pathological complete response (pCR) was achieved in eight patients (12.7 %). Overall down-staging was found in 49 patients (77.8 %). The 3-year disease-free survival (DFS) rate and overall survival (OS) rate was 76.2 % and 81.0 %, respectively. The most common adverse events during neoadjuvant treatment were acneiform skin rash (82.5 %), radiodermatitis (46.0 %), and diarrhea (36.5 %). KRAS mutations were detected in 19 of 63 (31.2 %) tumors. The down-staging rate in patients with KRAS wild-type (WT) was significantly higher than patients with KRAS mutation (P = 0.020). There was no significant difference in the pCR rate, 3-year DFS rate or 3-year OS rate between KRAS WT patients and KRAS-mutated patients. CONCLUSION: Neoadjuvant treatment with cetuximab and capecitabine-based chemoradiotherapy is safe and well tolerated. The pCR rate, 3-year DFS rate and OS rate are not superior to the rate of neoadjuvant chemoradiotherapy using two or more cytotoxic agents. The KRAS WT is highly associated with tumor down-staging to cetuximab plus capecitabine-based CRT in patients with LARC.

Hepatic veins anatomy and piggy-back liver transplantation.

BACKGROUND: The piggy-back caval anastomosis technique is widely used in orthotopic liver transplantation although it carries an increased risk of complications, including outflow obstruction and Budd-Chiari syndrome. The aim of this study is to clarify the anatomy and variations of hepatic veins (HVs) draining into the inferior vena cava (IVC), and to classify the surgical techniques of piggy-back liver transplantation (PBLT) based on the anatomy of HVs which can reduce the occurrence of complications. METHODS: PBLT was performed in 248 consecutive cases at our hospital from January 2004 to August 2011. The anatomy of recipients' HVs was determined when removing the native diseased livers. Both anatomy of HVs and short HVs draining into the IVC were recorded. These data were collected and analyzed. RESULTS: We classified anatomic variations of HVs in the 248 livers into five types according to the way of drainage into the IVC: type I (trunk type of left and middle HVs), 142 (57.3%) patients; type II (trunk type of right and middle HVs), 54 (21.8%); type III (trunk type of left, middle and right HVs), 14 (5.6%); type IV (non-trunk type of left, middle and right HVs), of which, type IVa, 16 (6.5%), in the same horizontal plane; type IVb, 18 (7.3%), in different horizontal planes; and type V (segment type), 4 (1.6%). The patients whose HVs anatomy belonged to types I, II and III underwent classical piggy-back liver transplantation. Type IVa patients had classical PBLT via HV venoplasty prior to piggy-back anastomosis, while type IVb patients and type V patients could only have modified PBLT. CONCLUSION: This study demonstrates that HVs can be classified according to the anatomy of their drainage into the IVC and we can use this classification to choose the best operative approach to PBLT.

Current status of sorafenib nanoparticle delivery systems in the treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and one of the leading causes of cancer-related death worldwide. Advanced HCC displays strong resistance to chemotherapy, and traditional chemotherapy drugs do not achieve satisfactory therapeutic efficacy. Sorafenib is an oral kinase inhibitor that inhibits tumor cell proliferation and angiogenesis and induces cancer cell apoptosis. It also improves the survival rates of patients with advanced liver cancer. However, due to its poor solubility, fast metabolism, and low bioavailability, clinical applications of sorafenib have been substantially restricted. In recent years, various studies have been conducted on the use of nanoparticles to improve drug targeting and therapeutic efficacy in HCC. Moreover, nanoparticles have been extensively explored to improve the therapeutic efficacy of sorafenib, and a variety of nanoparticles, such as polymer, lipid, silica, and metal nanoparticles, have been developed for treating liver cancer. All these new technologies have improved the targeted treatment of HCC by sorafenib and promoted nanomedicines as treatments for HCC. This review provides an overview of hot topics in tumor nanoscience and the latest status of treatments for HCC. It further introduces the current research status of nanoparticle drug delivery systems for treatment of HCC with sorafenib.

[Evaluation of the renal replacement therapy on the liver transplant patients with acute renal failure].

OBJECTIVE: To analyze the preoperative risk factors on liver transplant recipients with acute renal failure(ARF), and to evaluate renal replacement therapy (RRT) as a transitonary therapy before liver transplantation. METHODS: Liver transplant recipients with acute renal failure treated with renal replacement therapy between January 1st, 2001 and January 1st, 2008 in our center were retrospected. Clinical characteristics, the kinds of RRT and prognosis were analyzed; Logistic regression was applied to analyze the parameters that can forecast the motality of the liver transplant recipients with acute renal failure. RESULTS: Of the patients who received RRT, 30% survived to liver transplantation, 67.5% died while waiting for liver transplantation. The dead had a higher multiple organ dysfunction score (MODS), and lower mean arterial pressure than those survived to liver transplantation. There was no significant difference in the duration of RRT between continuous renal replacement therapy (CRRT) patients and hemodialysis patients. CRRT patients had a higher MODS, lower mean arterial pressure, lower serum creatinine than hemodialysis patients. Lower mean arterial pressure was statistically associated with higher risk of mortality. CONCLUSION: Though mortality was high, RRT helps part (30%) of patients survive to liver transplantation. Therefore, considering the high mortality without transplantation, RRT is acceptable for liver transplant recipients with ARF.

Liver support therapy with molecular adsorbents recirculating system in liver failure: a summary of 252 cases from 14 centers in China.

BACKGROUND: A liver support therapy, named molecular adsorbents recirculating system (MARS), has been used for more than 700 liver failure patients in China. We made here a summary to evaluate the effects of MARS treatment in different applications with emphasis on hepatitis B virus (HBV) based liver failure. METHODS: This report analyzed data of 252 patients (mean age (44.9+/- 12.7) years) in three groups: acute severe hepatitis (ASH), subacute severe hepatitis (SSH) and chronic severe hepatitis (CSH). The largest group was CSH (156 patients, 61.9%), and 188 patients (74.6%, 188/252) were infected with HBV. RESULTS: MARS treatments were associated with significant reduction of albumin bound toxins and water-soluble toxins. Most of the patients showed a positive response with a significant improvement of multiple organ function substantiated by a significant increase in prothrombin time activity (PTA) and median arterial pressure (MAP). There was a decrease in hepatic encephalopathy (HE) grade and Child-Turcotte-Pugh (CTP) scale. Thirty-nine of 188 HBV patients (20.7%) dropped out of the commendatory consecutive therapy ending with lower survival of 43.6% while the rest of the 149 patients had a survival rate of 62.4%. Survival within the ASH and SSH groups were 81.2% and 75.0%, respectively. In the CSH group, end stage patients were predominant (65/151, 43%), whereas the early and middle stage patients had a better prognosis: early stage survival, including orthotopic liver transplantation (OLT) survival of 91.7%, middle stage survival of 75%, end stage survival of 33.8%. CONCLUSIONS: MARS continues to be the most favorable extracorporeal treatment for liver support therapy in China for a wide range of conditions, including the majority of hepatitis B related liver failure conditions. The appropriate application of MARS for the right indications and stage of hepatic failure, as well as the fulfillment of prescribed treatments, will lead to the optimal therapeutic result.

[Piggy-back liver transplantation in treating acute liver failure patients: a report of 15 cases].

OBJECTIVE: To study the clinical significance of piggy-back liver transplantation in treating acute liver failure (ALF). METHODS: Fifteen ALF patients (13 caused by HBV and 2 with acute Wilson disease) had piggy-back liver transplantations (PBLT) in our hospital from Sept 1999 to Feb 2006. The outcomes of these patients were retrospectively analyzed. RESULTS: One year survival rate of the 15 patients was 87% (13/15). Excellent outcome was achieved in the 2 acute Wilson disease cases: their corneal Kayser-Fleischer rings disappeared and serum ceruloplasmin levels returned to normal. Among the 15 cases, one died of severe pulmonary infection and another died of multiple organ system failure on the 6th and 11th postoperative days. HBsAg positivity was observed in 13 cases before liver transplantation. Eleven patients survived and later received anti-HBV treatment recommended by the American Association for the Study of Liver Diseases. Their HBsAg became negative. CONCLUSION: Liver transplantation is an effective therapy for ALF and can improve survival rate significantly.

[Experience in the use of bronchofibroscopy in the treatment for acute lung injury after liver transplantation].

OBJECTIVE: To evaluate retrospectively the clinical therapeutic effects of the application of bronchofibroscopy(BFS) in the treatment of acute lung injury (ALI) after liver transplantation. METHODS: Fifty-eight patients with ALI caused by various kinds of reasons after liver transplantation were divided into two groups depending on whether the BFS was undertaken (group A, n=36) or not (group B, n=22), and the clinical therapeutic effects were evaluated by comparing the length of intensive care unit (ICU) stay and mechanical ventilation, mortality rate of ALI, morbidity and mortality rate of acute respiratory distress syndrome (ARDS) and changes in arterial blood gas analysis before and after BFS treatment. RESULTS: The length of ICU stay [(11+/-4) days vs. (16+/-4) days] and mechanical ventilation [(9+/-5) days vs. (14+/-5) days, both P<0.01] in group A were shorter, and mortality rate of ALI (11.1% vs. 36.4%), morbidity rate (27.8% vs. 54.5%, P<0.05 and P<0.01) and mortality rate of ARDS [40.0% (4/10) vs. 66.7% (8/12)] were lower in group A compared with group B (P>0.05). Arterial partial pressure of oxygen (PaO(2)), partial pressure of carbon dioxide (PaCO(2)), arterial oxygen saturation (SaO(2)), and oxygenation index (PaO(2)/FiO(2)) after treatment were much better than those before BFS in group A and the differences were significant (all P<0.01). CONCLUSION: BFS is a kind of safe and effective treatment measure for ALI after liver transplantation and is worthwhile to recommend.

[Ischemic postconditioning and its application in organ transplantation].

The concept of "ischemic postconditioning" was first raised in 2002, and the following 5 year research shows that it can protect organs from reperfusion injury. Although the mechanism of ischemic postconditioning is similar to ischemic preconditioning in many ways, it still has its own characteristics. Reperfusion injury is an inevitable problem in organ transplantation. It may accelerate the function recovery of the transplants to lessen the reperfusion injury. So ischemic postconditioning may have a fine prospect in organ transplantation for its good controllability during reperfusion. This article is going to briefly introduce the distinct mechanisms of ischemic postconditioning to protect organs from reperfusion injury and approach the possibilities of its application in organ transplantation.

[Effect of anti-ICOS monoclonal antibody combined with low-dose CsA on chronic rejection of heart grafts in rats].

OBJECTIVE: To evaluate the effect of anti-inducible costimulator monoclonal antibody (anti-ICOS-Ab) combined with low-dose cyclosporine (CsA) on the survival quality and chronic rejection of heart allografts in rats. METHODS: The rats' heterotopic cardiac transplantation model was established by Ono's method. The recipient rats were randomly divided into an isotransplantation control group and an allotransplantation experiment group. The experiment group was re-classified into a placebo group, a normal-dose CsA group, an anti-ICOS-Ab group, a low-dose CsA group, and an anti-ICOS-Ab combined with low-dose CsA group. The survival time of grafts was monitored. The cardiac grafts were harvested for histological analysis. Flow cytometric analysis was employed to detect the population of CD25+CD4+ in peripheral lymphocytes from recipients with a long-term surviving graft. RESULTS: The survival time of the cardiac allografts in CsA-treated groups was significantly longer than that in placebo group (P<0.05). The survival time of the cardiac allografts in anti-ICOS-Ab combined with low-dose CsA group was significantly longer than that in low dose CsA-treated group (P<0.05). There was no significant difference in the survival time of the cardiac grafts between the anti-ICOS-Ab group and the placebo group (P>0.05). Compared with the normal-dose CsA group, the chronic rejection lesions of the anti-ICOS-Ab combined with low-dose CsA treatment group significantly were alleviated in the long-term survival grafts, and the proportion of CD4+CD25+ regulatory T cell increased in peripheral blood. CONCLUSION: The anti-ICOS-Ab combined with low-dose CsA can prolong the survival of cardiac allografts and alleviate the chronic rejection significantly. The high expression level of CD4+CD25+ regulatory T cell is beneficial to the long-term survival of grafts.

Candidate Genes as Biomarkers in Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome Based on mRNA Expression Profile by Next-Generation RNA-Seq Analysis.

Up until now, the regulation mechanism at the level of gene during lipopolysaccharide- (LPS-) induced acute respiratory distress syndrome (ARDS) remains unclear. The discovery of differentially expressed genes (DEGs) between LPS-induced ARDS rats and normal rats by next-generation RNA sequencing analysis is of particular interest for the current study. These DEGs may help clinical diagnosis of ARDS and facilitate the selection of the optimal treatment strategy. Randomly, 20 rats were equally divided into 2 groups, the control group and the LPS group. Three rats from each group were selected at random for RNA sequencing analysis. Sequence reads were obtained from Illumina HiSeq4000 and mapped onto the rat reference genome RN6 using Hisat2. We identified 5244 DEGs (Fold_Change > 1.5, and P < 0.05) in the lung tissues from LPS-treated rats compared with normal rats, including 1413 upregulated and 3831 downregulated expressed genes. Lots of chemokine family members were among the most upregulated genes in LPS group. Gene ontology (GO) analysis revealed that almost all of the most enriched and meaningful biological process terms were mainly involved in the functions like immune-inflammation response and the pathways like cytokine-cytokine receptor interaction. We also found that, as for GO molecular function terms, the enriched terms were mainly related to chemokines and cytokines. DEGs with fold change over 100 were verified by quantitative real-time polymerase chain reaction and reanalyzed by gene-gene coexpression network, and the results elucidated central roles of chemokines in LPS-induced ARDS. Our results revealed some new biomarkers for uncovering mechanisms and processes of ARDS.

Parkin deficiency elevates hepatic ischemia/reperfusion injury accompanying decreased mitochondrial autophagy, increased apoptosis, impaired DNA damage repair and altered cell cycle distribution.

Hepatic ischemia/reperfusion injury (HIRI) serves a causative role in postoperative hepatocyte death; however, the mechanisms underlying HIRI remain unclear. Mitochondrial autophagy, with apoptosis, cell cycle distribution and DNA damage repair, may be regarded as a regulatory factor post­HIRI. Parkin, a novel ubiquitin ligase, has been reported to increase mitochondrial autophagy and decrease apoptosis. However, the association between Parkin, mitochondrial autophagy and other regulatory factors in HIRI is unclear. In the present study, the effects of Parkin on HIRI were investigated, using hepatocytes and livers from male Sprague Dawley rats subjected to simulated in vivo HIRI. The results of the present study demonstrated that Parkin expression and mitochondrial autophagy were upregulated post­HIRI, leading to decreased hepatocyte death. Parkin knockdown suppresses the level of mitochondrial autophagy and promotes hepatocyte apoptosis by suppressing apoptosis regulator Bcl­2 function post­HIRI. In addition, Parkin deficiency alters cell cycle distribution and impairs DNA damage repair post­HIRI. In conclusion, Parkin facilitates mitochondrial autophagy and DNA damage repair, inhibits apoptosis, and modulates the cell cycle, leading to increased hepatocyte survival, demonstrating that Parkin may act as a protective regulatory factor post HIRI.

Pedicled greater omentum flap for preventing bile leak in liver transplantation patients with poor biliary tract conditions.

BACKGROUND: Bile leak remains a main complication in liver transplantation patients with poor biliary tract conditions, mainly caused by an insufficient blood supply or dysplasia of the biliary tract. Although Roux-en-Y modus operandi can be adopted, the risk of other complications of the biliary tract such as infection increases. Using pedicled greater omentum flaps to wrap the anastomotic stoma, which increases the biliary tract blood supply, may reduce the incidence of bile leak. METHODS: Fourteen patients undergoing piggy-back liver transplantation and having poor biliary tract conditions were treated with pedicled greater omentum flaps to wrap the anastomotic stoma of the biliary tract. Their clinical data were analyzed retrospectively. RESULTS: Of the 14 patients, only one (7.1%) had a mild bile leak on the 8th day post-operation and fully recovered after symptomatic treatment. The other patients had no biliary complications. CONCLUSIONS: Using pedicled greater omentum flaps to wrap the anastomotic stoma of the biliary tract is an effective way to prevent bile leak in liver transplantation patients, especially those with poor biliary tract conditions. However, experience with this surgical technique still needs to be further explored.