Identification of ACAA1 and HADHB as potential prognostic biomarkers based on a novel fatty acid oxidation-related gene model in head and neck squamous cell carcinoma: A retrospective study.

OBJECTIVES: To investigate the importance of fatty acid oxidation (FAO)-related genes in predicting the progression and prognosis of head and neck squamous cell carcinoma (HNSCC). METHODS: The FAO-related gene prognostic model was established employing Cox regression analyses, during which accuracy and sensitivity of the gene model were evaluated in The Cancer Genome Atlas (TCGA) internal testing and Gene Expression Omnibus (GEO) external validation cohorts. Ultimately, hub genes were identified among 13 model genes using STRING and Cytoscape, with preliminary validation carried out through immunohistochemistry. RESULTS: The model, which comprised 13 genes (ABCD2, ACAA1, ACACB, AKT1, CNR1, CPT1C, CROT, ECHDC2, ETFA, HADHB, IRS2, LONP2, and SLC25A17), was established. On the basis of the median risk score, the two cohorts were grouped into low-and high-risk groups in the subsequent test and validation, and the former exhibited significantly higher survival rates than the latter. Nomograms were established based on prognostic factors, including stage and risk score, and individualized for the prediction of HNSCC patients. Ultimately, immunohistochemical staining showed that ACAA1 and HADHB were significantly under-expressed in HNSCC, with a favorable prognosis associated with low HADHB and high ACAA1. CONCLUSIONS: The gene prognostic model has illustrated promising capability in predicting the prognosis, and ACAA1 and HADHB might serve as potential therapeutic biomarkers for HNSCC patients.

Design, synthesis and biological evaluation of novel 9-methyl-9H-purine and thieno[3, 2-d]pyrimidine derivatives as potent mTOR inhibitors.

The mammalian target of rapamycin (mTOR) has been proved to be an effective target for cancer therapy. Two kinds of mTOR inhibitors, the rapalogs and mTOR kinase inhibitors (TORKi), have been developed and clinically validated in several types of malignancies. Compared with rapalogs, TORKi can exert better antitumor activity by inhibiting both mTORC1 and mTORC2, but the clinical development of current TORKi candidates has been relative slow, more TORKi with novel scaffold need to be developed to expand the current pipelines. In this study, a series of 9-methyl-9H-purine and thieno[3, 2-d]pyrimidine derivatives were designed, synthesized and biological evaluation. Most of these compounds exhibited good mTOR kinase inhibitory activity and selectivity over PI3Kα. Subsequent antiproliferative assay allowed us to identify the lead compound 15i, which display nanomolar to low micromolar IC50s against six human cancer cell lines. 15i could induce cell cycle arrest of MCF-7, PC-3 and A549 cells at the G0/G1 phase and suppress the migration and invasion of these cancer cells by suppressing the phosphorylation of AKT and P70S6 kinase. It could also regulate autophagy-related proteins to induce autophagy. Therefore, 15i would be a starting point for the development of new TORKi as anticancer drug.

Identification of a selective BRD4 PROTAC with potent antiproliferative effects in AR-positive prostate cancer based on a dual BET/PLK1 inhibitor.

BRD4-targeted proteolysis targeting chimera (PROTAC) have exhibited promising in vitro and in vivo anticancer activity in a number of cancer models. However, the clinical development of current reported BRD4-PROTACs have stagnated, largely due to the safety risks caused by their poor degradation selectivity. In this study, we designed and synthesized a series of PROTACs based on our recently reported dual BET/PLK1 inhibitor WNY0824, which led to the discovery of an isoform-selective and potent BRD4-PROTAC 12a (WWL0245). WWL0245 exhibited excellent selective cytotoxicity in the BETi sensitive cancer cell lines, including AR-positive prostate cancer cell lines. It could also efficiently induce ubiquitin-proteasomal degradation of BRD4 in AR-positive prostate cancer cell lines, with sub-nanomolar half-maximal degrading concentration (DC50) and maximum degradation (Dmax) > 99%. Moreover, WWL0245 induced cell cycle arrest at the G0/G1 phase and apoptosis in AR-positive prostate cancer by downregulation of the protein levels of AR, PSA and c-Myc as well as transcriptionally suppressed AR-regulated genes. WWL0245 was thus expected to be developed as a promising drug candidate for AR-positive prostate cancer and a valuable tool compound to study the biological function of BRD4.

Exercise-Training Regulates Apolipoprotein B in Drosophila to Improve HFD-Mediated Cardiac Function Damage and Low Exercise Capacity.

Apolipoprotein B plays an essential role in systemic lipid metabolism, and it is closely related to cardiovascular diseases. Exercise-training can regulate systemic lipid metabolism, improve heart function, and improve exercise capacity, but the molecular mechanisms involved are poorly understood. We used a Drosophila model to demonstrate that exercise-training regulates the expression of apoLpp (a homolog of apolipoprotein B) in cardiomyocytes, thereby resisting heart insufficiency and low exercise capacity caused by obesity. The apoLpp is an essential lipid carrier produced in the heart and fat body of Drosophila. In a Drosophila genetic screen, low expression of apoLpp reduced obesity and cardiac dysfunction induced by a high-fat diet (HFD). Cardiac-specific inhibition indicated that reducing apoLpp in the heart during HFD reduced the triglyceride content of the whole-body and reduced heart function damage caused by HFD. In exercise-trained flies, the result was similar to the knockdown effect of apoLpp. Therefore, the inhibition of apoLpp plays an important role in HFD-induced cardiac function impairment and low exercise capacity. Although the apoLpp knockdown of cardiomyocytes alleviated damage to heart function, it did not reduce the arrhythmia and low exercise capacity caused by HFD. Exercise-training can improve this condition more effectively, and the possible reason for this difference is that exercise-training regulates climbing ability in ways to promote metabolism. Exercise-training during HFD feeding can down-regulate the expression of apoLpp, reduce the whole-body TG levels, improve cardiac recovery, and improve exercise capacity. Exercise-training can downregulate the expression of apoLpp in cardiomyocytes to resist cardiac function damage and low exercise capacity caused by HFD. The results revealed the relationship between exercise-training and apoLpp and their essential roles in regulating heart function and climbing ability.

The effect of aging on VEGF/VEGFR2 signal pathway genes expression in rat liver sinusoidal endothelial cell.

Liver sinusoidal endothelial cells (LSECs) play a key role in the initiation and neoangiogenesis of liver regeneration. We presume that the abnormity of the VEGF/VEGFR2 and its pathway gene Id1, Wnt2 and HGF expression in aged LSECs may be an important mechanism to affect liver regeneration of the elderly. LSECs from two different groups (adult and old) were isolated in a rodent model, and observed by SEM and TEM. The adult and old rats were underwent 70% partial hepatectomy. The proliferation of hepatocytes and LSECs were analyzed by Immunofluorescence staining. The expression of VEGF/VEGFR2 and its pathway gene in isolated LSECs and liver tissue after hepatectomy were detected by qRT-PCR and Western blot. There is a decreased number of endothelial fenestrae in the LSECs of the old group, compared to the adult group. The old group had a lower expression of VEGF/VEGFR2 and its pathway gene than the adult groups (p < 0.01). The results of western blot were consistent with those of qRT-PCR. The hepatocytes had a high proliferation rate at first 4 days after hepatectomy, and a significantly higher proliferation rate in the adult group. The LSECs began to proliferate after 4 days of hepatectomy, and showed a quantity advantage in the adult group. The adult group had a significantly higher expression of VEGF/VEGFR2 and its pathway gene after hepatectomy than the old group (p < 0.01). LSCEs turn to be defenestration in structure and have a low expression of VEGF/VEGFR2 and its pathway gene with aging.

Identification of a potent and selective phosphatidylinositol 3-kinase δ inhibitor for the treatment of non-Hodgkin's lymphoma.

PI3Kδ has proved to be an effective target for anti-lymphoma drugs. However, the application of current approved PI3Kδ inhibitors has been greatly limited due to their specific immune-mediated toxicity and increased risk of infection, it is necessary to develop more PI3Kδ inhibitors with new scaffold. In this study, SAR study with respect to piperazinone-containing purine derivatives led to the discovery of a potent and selective PI3Kδ inhibitor, 4-(cyclobutanecarbonyl)-1-((2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methyl)piperazin-2-one (WNY1613). WNY1613 exhibits good antiproliferative activity against a panel of non-Hodgkin's lymphoma (NHL) cell lines by inducing cancer cell apoptosis and inhibiting the phosphorylation of PI3K and MAPK downstream components. In addition, it can also prevent the tumor growth in both SU-DHL-6 and JEKO-1 xenograft models without observable toxicity. WNY1613 thus could be developed as a promising candidate for the treatment of NHL after subsequent extensive pharmacodynamics and pharmacokinetics investigation.

Design, synthesis and structure-activity relationship study of piperazinone-containing thieno[3,2-d]pyrimidine derivatives as new PI3Kδ inhibitors.

Two classes of piperazinone-containing thieno[3,2-d]pyrimidines were designed and synthesized as new PI3Kδ inhibitors in this study. Detailed SAR study with respect to the piperazinone substituents at the 6-position of thieno[3,2-d]pyrimidine core demonstrated that piperazinone-containing thieno[3,2-d]pyrimidines would be more potent and selective for PI3Kδ than their piperazine counterparts, which led to the discovery of several potent PI3Kδ inhibitors with comparable or better antiproliferative activity against a panel of non-Hodgkin lymphoma (NHL) cell lines as compared with idelalisib. Our study will promote the development of new PI3Kδ inhibitors based on piperazinone-containing thieno[3,2-d]pyrimidine scaffold.

Clonal integration in Phragmites australis alters soil microbial communities in an oil-contaminated wetland.

Clonal plants can share information and resources among connected ramets (asexual individuals). Such clonal integration can promote ramet growth, which may further influence soil microbial communities in the rooting zone. Crude oil contamination can negatively affect plant growth and alter soil microbial community composition. However, we still know little about how clonal integration affects soil microbial communities, especially under crude oil contamination. In a coastal wetland, ramets of the rhizomatous plant Phragmites australis in circular plots (60 cm in diameter) were subjected to 0, 5 and 10 mm depth of crude oil, and the rhizomes at the edge of the plots were either severed (preventing clonal integration) or left intact (allowing clonal integration). After three years of treatment, we analysed in each plot soil physiochemical properties and soil microbial community composition. The alpha-diversity of the soil microbial communities did not differ between intact and severed plots, but was overall lower in 10-mm than in 0-mm and 5-mm oil plots. Considering all three oil treatments together, soil microbial community dissimilarity (beta-diversity) was positively correlated with soil property distance in both severed and intact plots. Considering the three oil treatments separately, this pattern was also observed in 10-mm oil plots, but not in 0-mm or 5-mm oil plots. The soil microbial community composition was more sensitive to the oil addition than to the clonal integration. Moreover, the relative abundance of the nitrogen-cycling bacterial taxa was lower in intact than in severed plots, and that of the oil-degrading bacterial taxa increased with increasing oil-addition levels. Our results indicate that clonal integration and oil contamination can influence soil microbial communities independently through changing the relative abundance of the component bacteria taxa, which has important implications for ecosystem functions of the soil food web mediated by clonal plants.

Efficacy of ixazomib for the treatment of relapsed/refractory multiple myeloma: A protocol of systematic review and meta-analysis.

BACKGROUND: Over the past years, ixazomib has been increasingly explored for the treatment of relapsed/refractory multiple myeloma (RRMM). However, its results are still contradictory. This study will explore the efficacy and safety of ixazomib for patients with RRMM. METHODS: A systematic records search of Cochrane Library, PUBMED, EMBASE, CINAHL, ACMD, PsycINFO, WANGFANG, and China National Knowledge Infrastructure will be carried out from their origin to March 31, 2020 with no limitations of language and publication status. Trials will be selected by titles/abstracts, and full manuscripts by 2 independent authors. Data collection will be carried out from eligible trials based on the previous designed criteria. Study quality will be checked using Cochrane risk of bias, and statistical analysis will be administered by RevMan 5.3 software. RESULTS: This study will summarize the current high-quality trials investigating the efficacy and safety of ixazomib for the treatment of patients with RRMM. CONCLUSION: The results of this study may provide convinced evidence on the evidence-based medicine level, and guidance for clinical practice and future studies. INPLASY REGISTRATION NUMBER: INPLASY202040027.

Design, synthesis, and biological evaluation of 4,5-dihydro-[1,2,4]triazolo[4,3-f]pteridine derivatives as novel dual-PLK1/BRD4 inhibitors.

Protein kinase inhibitors and epigenetic regulatory molecules are two main kinds of anticancer drugs developed in recent years. Both kinds of drugs harbor their own advantages and disadvantages in the treatment of cancer, and the development of small molecules which could target at kinases and epigenetic targets simultaneously can avoid the defects of drugs which only targets at kinases or epigenetic proteins. In this study, a series of 4,5-dihydro-[1,2,4]triazolo [4,3-f]pteridine derivatives were designed and synthesized based on the structure of PLK1 inhibitor BI-2536. Subsequent targets affinity screen and antiproliferative activity test led to the discovery of the most potent dual PLK1/BRD4 inhibitor 9b with good potency for both PLK1 (IC50 = 22 nM) and BRD4 (IC50 = 109 nM) as well as favorable antiproliferative activity against a panel of cancer cell lines. 9b could induce cell cycle arrest and apoptosis in acute myeloid leukemia cell line MV 4-11 in a concentration dependent manner. It could also downregulate the transcription of several proliferation-related oncogenes, including c-MYC, MYCN and BCL-2. Finally, in a MV4-11 mouse xenograft model, 9b exhibited favorable in vivo antitumor activity with 66% tumor growth inhibition (TGI) at a dose of 60 mg/kg while without obvious toxicity. This study thus provided us a start point for the development of new dual PLK1/BRD4 inhibitors as anticancer agents.

Preoperative γ-glutamyl transpeptidase to platelet ratio (GPR) is an independent prognostic factor for HBV-related hepatocellular carcinoma after curative hepatic resection.

Liver fibrosis and cirrhosis is associated with the prognosis of patients with hepatocellular carcinoma (HCC) after treatment. The γ-glutamyl transpeptidase to platelet ratio (GPR) is reported to predict significant liver fibrosis and cirrhosis. The aim of this study was to investigate the predictive value of preoperative GPR on the recurrence and survival of patients with HCC who underwent curative hepatectomy.A retrospective review of demographics, medical records, and prognosis of patients with hepatitis B virus (HBV)-related HCC was performed. Overall survival (OS) and disease-free survival (DFS) were evaluated using Kaplan-Meier method, and the log-rank test was used to analyze differences in recurrence and survival. Univariate and multivariate analyses were used for significance of prognostic factor.A total of 357 patients with HBV-related HCC were included in this analysis. The preoperative GPR was associated with recurrence and survival rates, independent of HCC progression or tumor marker levels, in a multivariate analysis. OS was higher in patients with a GPR <0.84 versus ≥084 (5-year survival rates 58.6% vs. 38.5%; P < 0.001). DFS was also worse in patients with a GPR ≥0.84 than in those with GPR <0.84 (5-year recurrence rates 42.8% vs. 22.8%; P < 0.001).GPR score of ≥0.84 represents a major risk factor for the poor prognosis for HBV-related HCC after hepatic resection, and GPR served as an independent predictive factor for HBV-related HCC OS.

The value of the combination of fibrosis index based on the four factors and future liver remnant volume ratios as a predictor on posthepatectomy outcomes.

BACKGROUND: Liver fibrosis and cirrhosis are well-known risk factors for morbidity and mortality after hepatectomy. Fibrosis index based on the four factors (FIB-4) is a non-invasive method for detection of hepatic fibrosis and cirrhosis with high accuracy. This study aimed to evaluate the predictive value of future liver remnant volume ratios (FLRVR)/FIB-4 after liver resection for posthepatectomy outcomes in patients with fibrosis and cirrhosis. METHODS: All patients with severe fibrosis or cirrhosis who underwent a liver resection (≥2 segments) were included. Liver insufficiency was defined according to grade C posthepatectomy liver failure (PLF) proposed by the International Study Group of Liver Surgery (ISGLS). Receiver operating characteristic curves and logistic regression model were used to determine the optimal cutoff of FLRVR/FIB-4 and independent risk factors of postoperative outcomes. RESULTS: The study population consisted of 338 patients. FLRVR/FIB-4 was gradually correlated with short-term outcomes. The optimal value of FLRVR/FIB-4 to predict PLF was 0.13 when considering grade C PLF and postoperative death. A value of 0.24 best predicted postoperative morbidity. At multivariate analysis, FLRVR/FIB-4 remained an independent predictor of PLF (risk ratio(RR) = 0.046; 95% confidence interval (CI): 0.010-0.215; P < 0.001), postoperative morbidity (RR = 0.272; 95% CI: 0.167-0.445; P < 0.001) and mortality(RR =0.058; 95% CI: 0.012-0.277; P < 0.001). CONCLUSION: FLRVR/FIB-4 is an independent predictive factor of postoperative outcomes after liver resection in patients with cirrhosis. It is a useful preoperative investigation for risk stratification before hepatectomy.

Screening for differentially expressed genes in endophytic fungus strain 39 during co-culture with herbal extract of its host Dioscorea nipponica Makino.

Strain 39 is an endophytic fungus which was isolated from Dioscorea nipponica Makino (DNM). After Strain 39 co-cultured with ethanol extract of DNM rhizomes for several days, the content of saponins in this culture mixture would be obviously increased. To analyze the mechanism of this microbial transformation, we used the differential display reverse transcription polymerase chain reaction (DDRT-PCR) method to compare the transcriptomes between Strain 39 cultured in normal PD medium and in PD medium which added ethanol extract of DNM rhizomes. We amplified 29 DDRT-PCR bands using 12 primer combinations of three anchored primers and five random primers, and six bands were re-amplified. Analysis of real-time PCR and sequence alignment showed that three clones were up-regulated in sample group: squalene epoxidase, squalene synthase, and catalase, one clone was expressed only in sample group. The possible roles and origins of the above genes were discussed, and the molecular mechanism of Strain 39 biotransformation was speculated. This study is the first report of the molecular biotransformation mechanism of saponins production by endophytic fungus of DNM.

Major hepatectomy is safe for hepatocellular carcinoma in elderly patients with cirrhosis.

BACKGROUND: Because of an increasing aging population worldwide, a greater number of elderly patients are being considered for hepatic resection. The objective of this retrospective pair-matched study was to assess the influence of age on postoperative outcomes after major hepatectomy (resection of three or more Couinaud segments) in elderly patients with hepatocellular carcinoma (HCC) and cirrhosis. PATIENTS AND METHODS: A retrospective review of patient demographics, diagnoses, surgical treatments, and early postoperative outcomes was performed. RESULTS: A total of 208 HCC patients with cirrhosis underwent major hepatectomy between 2007 and 2012. The mortality rate was 3.57% in patients aged 70 years or more (group E) compared with 1.32% in those aged below 70 years (group Y; P=0.630). The overall complication rates were 53.57% in group E and 47.37% in group Y (P=0.427). Increasing age was independently associated with postoperative pneumonia (P<0.001), bacteremia (P=0.026), and respiratory failure requiring reintubation (P=0.028). A total of 25.00% of patients had a Clavien-Dindo classification grade of 3a or more in group E compared with 13.16% in group Y (P=0.040). In multivariate analysis, intraoperative red blood cell transfusion of 5 U or more (P=0.016; hazard ratio 4.812; 95% confidence interval 1.332-17.384) was a predictor of higher morbidity in the elderly. CONCLUSION: With rigorous screening of patients and improvement of perioperative management and operative techniques, major hepatectomy can be safely performed on HCC patients aged 70 years or more with liver cirrhosis. Intraoperative red blood cell transfusion of 5 U or more was predictive of higher morbidity in the elderly. Surgeons should take care to minimize the likelihood of intraoperative blood transfusion in elderly patients.

Pig-islet xenotransplantation: recent progress and current perspectives.

Islet xenotransplantation is one prospective treatment to bridge the gap between available human cells and needs of patients with diabetes. Pig represents an ideal candidate for obtaining such available cells. However, potential clinical application of pig islet still faces obstacles including inadequate yield of high-quality functional islets and xenorejection of the transplants. Adequate amounts of available islets can be obtained by selection of a suitable pathogen-free source herd and the development of isolation and purification method. Several studies demonstrated the feasibility of successful preclinical pig-islet xenotransplantation and provided insights and possible mechanisms of xenogeneic immune recognition and rejection. Particularly promising is the achievement of long-term insulin independence in diabetic models by means of distinct islet products and novel immunotherapeutic strategies. Nonetheless, further efforts are needed to obtain much more safety and efficacy data to translate these findings into clinic.

Prognostic role of neutrophil-to-lymphocyte ratio in colorectal cancer: a systematic review and meta-analysis.

The prognostic role of inflammation index like neutrophil-to-lymphocyte ratio (NLR) in colorectal cancer (CRC) remains controversial. We conduct a meta-analysis to determine the predictable value of NLR in the clinical outcome of CRC patients. The analysis was carried out based on the data from 16 studies (19 cohorts) to evaluate the association between NLR and overall survival (OS) and progression-free survival (PFS) in patients with CRC. In addition, the relationship between NLR and clinicopathological parameters was assessed. Hazard ratio (HR) or odds ratio (OR) with its 95% confidence interval (CI) was used as the effect size estimate. Our analysis results indicated that elevated pretreatment NLR predicted poorer OS (HR: 1.813, 95% CI: 1.499-2.193) and PFS (HR: 2.102, 95% CI: 1.554-2.843) in patients with CRC. Increased NLR is also significantly associated with the poorer differentiation of the tumor (OR: 1.574, 95% CI: 1.226-2.022) and higher carcino-embryonie antigen (CEA) level (OR: 1.493, 95% CI: 1.308-1.705). By these results, we conclude that NLR gains a prognostic value for patients with CRC. NLR should be monitored in CRC patients for rational stratification of the patients and adjusting the treatment strategy.

Ischemic preconditioning versus intermittent clamping of portal triad in liver resection: A meta-analysis of randomized controlled trials.

AIM: To compare the clinical outcome of patients undergoing liver resection under ischemic preconditioning (IP) versus intermittent clamping (IC). METHODS: A systematic published work search was conducted to detect randomized controlled trials (RCT) comparing IP and intermittent clamping of the portal triad. A meta-analysis was conducted to estimate postoperative morbidity and mortality, blood loss, transfusion requirement, and liver injury based on the levels of bilirubin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Meta-analysis was performed using either the fixed-effects model or random-effects model. RESULTS: Five RCT published between 2006 and 2012 containing a total of 403 patients were eligible for final analysis. Meta-analysis of operative time showed it was lower in the IP group than the IC group with weighted mean difference (WMD) of -18.23 (95% confidence interval (CI), -28.58 to -7.87; P = 0.0006). Meta-analysis of ALT levels indicated lower levels in the IP group on postoperative days 3 and 7 (WMD on day 3: -45.27, 95% CI, -49.92 to -40.62; P < 0.00001; I(2) = 0%; WMD on day 7: -24.33, 95% CI, -28.04 to -20.62; P < 0.00001; I(2) = 0%). Meta-analyses revealed no significant difference in blood loss, transfusion requirement, mortality, morbidity, ischemic duration, hospital stay, AST and bilirubin levels on postoperative days 1, 3 and 7, and ALT levels on postoperative day 1 between IP and IC groups. CONCLUSION: On currently available evidence, IP does not offer a satisfying benefit to patients undergoing hepatic resection. However, they have lower operative time and less liver injury after liver resections.

Diagnosis and treatment of hepatic tuberculosis: report of five cases and review of literature.

Hepatic tuberculosis is uncommon, lack of specific clinical manifestations and imaging features, so it can easily be misdiagnosed in clinical. Herein, we discuss variety of its forms and summarize the diagnosis and treatment of hepatic tuberculosis in this paper. Five cases of hepatic tuberculosis are described. The diagnosis, treatment and outcome of the patients are discussed. Image examination associated with image-guided fine needle aspiration biopsy is the best diagnostic method. In our center, three patients underwent needle biopsy and confirmed hepatic tuberculosis. In addition, two patients preoperative misdiagnosed as cholangiocarcinoma were confirmed hepatic tuberculosis by postoperative pathology. Three patients underwent surgical procedures along with anti-tubercular drug therapy, two patients received only anti-tubercular drug therapy. The renal post-transplantation patient with hepatic tuberculosis eventually died of multiple organ failure (MODS). The other four patients were followed for 48~120 months, yielding no recurrence of hepatic tuberculosis. In conclusion, hepatic tuberculosis usually associated with atypical clinical manifestations. Image examination associated with image-guided fine needle aspiration biopsy is the best diagnostic method. Anti-TB treatment is effective in most of cases. However, if there are indications for surgery or difficult to diagnose, surgical procedures along with anti-tubercular drug therapy could be adopted.

Treatment of late biliary stricture after blunt abdominal trauma.

BACKGROUND: Extrahepatic bile duct injury from blunt abdominal trauma is severe and very rare. However, no definitive treatment has been proposed for biliary strictures caused by blunt abdominal trauma. METHODS: Four cases of late biliary stricture following the initial repair of the liver rupture because of the blunt abdominal trauma are described. The diagnosis, treatment, and outcome of the complications are discussed. RESULTS: One patient received bile drainage because of biliary peritonitis on admission. He underwent a right hepatectomy and a Roux-en-Y anastomosis on the left bile duct because of right lobar atrophy 3 months later. Cholangiojejunostomy was performed in the other three patients using the Hepp-Couinaud technique. The patients were followed for 5-37 months, yielding no recurrence of the biliary stricture or cholangitis. CONCLUSION: Surgical intervention should be used after the failure of repeating endoscopic stenting or percutaneous drainage. The Hepp-Couinaud technique could provide a wide and accurate leakproof mucosa-to-mucosa anastomosis that is responsible for excellent results.