Acute suppurative terminal cholangitis:Clinical characteristics of a new subtype of acute cholangitis

Background:Acute suppurative terminal cholangitis(ASTC)is rarer than acute obstructive cholangitis and is not well studied.To explore this subtype of acute cholangitis,we described our clinical experience with ASTC.Methods:We performed a retrospective review of patients with ASTC admitted to our center from September 2014 to August 2020.We analyzed their clinical characteristics,including etiology,clinical manifestations,imaging features,treatment and prognosis.Results:A total of 32 ASTC patients were included in the analysis.The majority of the patients had a history of biliary operations,and clinical manifestations were occult and atypical.The positive rate of bacterial culture was 46.9%.All the patients had typical imaging features on computed tomography and magnetic resonance imaging.Treatment with effective antibiotics was provided as soon as diagnosis was established.After treatment,most patients had a good outcome.Elevated levels of total bilirubin,aspartate aminotransferase,procalcitonin and gamma-glutamyltransferase were the characteristics of critically ill patients and were associated with relatively poor prognosis.Conclusions:Our results demonstrated that ASTC should be recognized as a new subtype of acute cholangitis,and that earlier diagnosis and more personalized treatments are needed.

Development and validation of a nomogram model for predicting the risk of gallstone recurrence after gallbladder-preserving surgery

Background:The high incidence of gallstone recurrence was a major concern for laparoscopic gallbladderpreserving surgery.This study aimed to investigate the risk factors for gallstone recurrence after gallbladder-preserving surgery and to establish an individualized nomogram model to predict the risk of gallstone recurrence.Methods:The clinicopathological and follow-up data of 183 patients who were initially diagnosed with gallstones and treated with gallbladder-preserving surgery at our hospital from January 2012 to January 2019 were retrospectively collected.The independent predictive factors for gallstone recurrence following gallbladder-preserving surgery were identified by multivariate logistic regression analysis.A nomogram model for the prediction of gallstone recurrence was constructed based on the selected variables.The C-index,receiver operating characteristic(ROC)curve and calibration curve were used to evaluate the predictive power of the nomogram model for gallstone recurrence.Results:During the follow-up period,a total of 65 patients experienced gallstone recurrence,and the recurrence rate was 35.5%.Multivariate logistic regression analysis revealed that the course of gallstones>2 years[odds ratio(OR)=2.567,95%confidence interval(CI):1.270-5.187,P=0.009],symptomatic gallstones(OR=2.589,95%CI:1.059-6.329,P=0.037),multiple gallstones(OR=2.436,95%CI:1.133-5.237,P=0.023),history of acute cholecystitis(OR=2.778,95%CI:1.178-6.549,P=0.020)and a greasy diet(OR=2.319,95%CI:1.186-4.535,P=0.014)were independent risk factors for gallstone recurrence after gallbladder-preserving surgery.A nomogram model for predicting the recurrence of gallstones was established based on the above five variables.The results showed that the C-index of the nomogram model was 0.692,suggesting it was valuable to predict gallstone recurrence.Moreover,the calibration curve showed good consistency between the predicted probability and actual probability.Conclusions:The nomogram model for the prediction of gallstone recurrence might help clinicians develop a proper treatment strategy for patients with gallstones.Gallbladder-preserving surgery should be cautiously considered for patients with high recurrence risks.

High Seebeck Coefficient Thermally Chargeable Supercapacitor with Synergistic Effect of Multichannel Ionogel Electrolyte and Ti_(3)C_(2)T_(x) MXene-Based Composite Electrode

Thermally chargeable supercapacitors can collect low-grade heat generated by the human body and convert it into electricity as a power supply unit for wearable electronics.However,the low Seebeck coefficient and heat-to-electricity conversion efficiency hinder further application.In this paper,we designed a high-performance thermally chargeable supercapacitor device composed of ZnMn_(2)O_(4)@Ti_(3)C_(2)T_(x)MXene composites(ZMO@Ti_(3)C_(2)T_(x) MXene)electrode and UIO-66 metal–organic framework doped multichannel polyvinylidene fluoridehexafluoro-propylene ionogel electrolyte,which realized the thermoelectric conversion and electrical energy storage at the same time.This thermally chargeable supercapacitor device exhibited a high Seebeck coefficient of 55.4 mV K^(−1),thermal voltage of 243 mV,and outstanding heat-to-electricity conversion efficiency of up to 6.48%at the temperature difference of 4.4 K.In addition,this device showed excellent charge–discharge cycling stability at high-temperature differences(3 K)and low-temperature differences(1 K),respectively.Connecting two thermally chargeable supercapacitor units in series,the generated output voltage of 500 mV further confirmed the stability of devices.When a single device was worn on the arm,a thermal voltage of 208.3 mV was obtained indicating the possibility of application in wearable electronics.

Hepatomegaly and jaundice as the presenting symptoms of systemic light-chain amyloidosis: A case report

BACKGROUND Light chain(AL)amyloidosis is a plasma cell dyscrasia characterized by the pathologic production and extracellular tissue deposition of fibrillar proteins derived from immunoglobulin AL fragments secreted by a clone of plasma cells,which leads to progressive dysfunction of the affected organs.The two most commonly affected organs are the heart and kidneys,and liver is rarely the dominant affected organ with only 3.9%of cases,making them prone to misdia-gnosis and missed diagnosis.CASE SUMMARY A 65-year-old woman was admitted with a 3-mo history of progressive jaundice and marked hepatomegaly.Initially,based on enhanced computed tomography scan and angiography,Budd-Chiari syndrome was considered and balloon dilatation of significant hepatic vein stenoses was performed.However,addi-tional diagnostic procedures,including liver biopsy and bone marrow-exami-nation,revealed immunoglobulin kapa AL amyloidosis with extensive liver involvement and hepatic vascular compression.The disease course was progre-ssive and fatal,and the patient eventually died 5 mo after initial presentation of symptoms.CONCLUSION AL amyloidosis with isolated liver involvement is very rare,and can be easily misdiagnosed as a vascular disease.

Comprehensive prognostic and immune analysis of sterol Oacyltransferase 1 in patients with hepatocellular carcinoma

BACKGROUND Sterol O-acyltransferase 1(SOAT1)is an important target in the diagnosis and treatment of liver cancer.However,the prognostic value of SOAT1 in patients with hepatocellular carcinoma(HCC)is still not clear.AIM To investigate the correlation of SOAT1 expression with HCC,using RNA-seq and gene expression data of The Cancer Genome Atlas(TCGA)-liver hepatocellular carcinoma(LIHC)and pan-cancer.METHODS The correlation between SOAT1 expression and HCC was analyzed.Cox hazard regression models were conducted to investigate the prognostic value of SOAT1 in HCC.Overall survival and disease-specific survival were explored based on TCGA-LIHC data.Biological processes and functional pathways mediated by SOAT1 were characterized by gene ontology(GO)analysis and the Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis of differentially expressed genes.In addition,the protein-protein interaction network and co-expression analyses of SOAT1 in HCC were performed to better understand the regulatory mechanisms of SOAT1 in this malignancy.RESULTS SOAT1 and SOAT2 were highly expressed in unpaired samples,while only SOAT1 was highly expressed in paired samples.The area under the receiver operating characteristic curve of SOAT1 expression in tumor samples from LIHC patients compared with para-carcinoma tissues was 0.748,while the area under the curve of SOAT1 expression in tumor samples from LIHC patients compared with GTEx was 0.676.Patients with higher SOAT1 expression had lower survival rates.Results from GO/KEGG and gene set enrichment analyses suggested that the PI3K/AKT signaling pathway,the IL-18 signaling pathway,the calcium signaling pathway,secreted factors,the Wnt signaling pathway,the Jak/STAT signaling pathway,the MAPK family signaling pathway,and cell–cell communication were involved in such association.SOAT1 expression was positively associated with the abundance of macrophages,Th2 cells,T helper cells,CD56bright natural killer cells,and Th1 cells,and negatively linked to the abundance of Th17 cells,dendritic cells,and cytotoxic cells.CONCLUSION Our findings demonstrate that SOAT1 may serve as a novel target for HCC treatment,which is helpful for the development of new strategies for immunotherapy and metabolic therapy.

Electrospraying Si/SiO_(x)/C and Sn/C nanosphere arrays on carbon cloth for high-performance flexible lithium-ion batteries

Exploring electrode materials with larger capacity,higher power density and longer cycle life was critical for developing advanced flexible lithium-ion batteries(LIBs).Herein,we used a controlled two-step method including electrospraying followed with calcination treatment by CVD furnace to design novel electrodes of Si/Si_(x)/C and Sn/C microrods array consisting of nanospheres on flexible carbon cloth substrate(denoted as Si/Si_(x)/C@CC,Sn/C@CC).Microrods composed of cumulated nanospheres(the diameter was approximately 120 nm)had a mean diameter of approximately 1.5μm and a length of around 4.0μm,distributing uniformly along the entire woven carbon fibers.Both of Si/Si/Si_(x)/C@CC and Sn/C@CC products were synthesized as binder-free anodes for Li-ion battery with the features of high reversible capacity and excellent cycling.Especially Si/Six/C electrode exhibited high specific capacity of about 1750 mA∙h∙g^(−1)at 0.5 A∙g^(−1)and excellent cycling ability even after 1050 cycles with a capacity of 1388 mA∙h∙g^(−1).Highly flexible Si/Si_(x)/C@CC//LiCoO_(2)batteries based on liquid and solid electrolytes were also fabricated,exhibiting high flexibility,excellent electrical stability and potential applications in flexible wearable electronics.

Value of radiofrequency ablation in the treatment of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a malignant disease that substantially affects public health worldwide.It is especially prevalent in east Asia and sub-Saharan Africa,where the main etiology is the endemic status of chronic hepatitis B.Effective treatments with curative intent for early HCC include liver transplantation,liver resection(LR),and radiofrequency ablation(RFA).RFA has become the most widely used local thermal ablation method in recent years because of its technical ease,safety,satisfactory local tumor control,and minimally invasive nature.This technique has also emerged as an important treatment strategy for HCC in recent years.RFA,liver transplantation,and hepatectomy can be complementary to one another in the treatment of HCC,and the outcome benefits have been demonstrated by numerous clinical studies.As a pretransplantation bridge therapy,RFA extends the average waiting time without increasing the risk of dropout or death.In contrast to LR,RFA causes almost no intraabdominal adhesion,thus producing favorable conditions for subsequent liver transplantation.Many studieshave demonstrated mutual interactions between RFA and hepatectomy,effectively expanding the operative indications for patients with HCC and enhancing the efficacy of these approaches.However,treated tumor tissue remains within the body after RFA,and residual tumors or satellite nodules can limit the effectiveness of this treatment.Therefore,future research should focus on this issue.

Diagnosis and management of autoimmune pancreatitis:Experience from China

AIM： To determine the clinical, radiographic and pathologic characteristics, diagnostic and treatment modalities in patients with autoimmune pancreatitis （AIP）. METHODS： In this retrospective study, the data of patients with diagnosed chronic pancreatitis （CP） between 1995 and 2006 in Chinese PLA General Hospital were included to screen for the cases with AIP, according to the following diagnostic criteria： （1） diagnostic histopathologic features, and abound IgG4-positive plasma cells on pancreatic tissues; （2） characteristic imaging on computed tomography and pancreatography, together with increased serum IgG, y-globulin levels or presence of autoantibodies; （3） response to steroid therapy. The clinical, radiographic and pathologic characteristics, diagnostic and treatment modalities, and outcome of AIP cases were reviewed. RESULTS： Twenty-five （22 male, 3 female; mean age 54 years, 36-76 years） out of 510 CP patients were diagnosed as AIP, which accounted for 49% （21/43） of CP population undergoing surgical treatment in the same period. The main clinical manifestations included intermittent or progressive jaundice in 18 cases （72%）, abdominal pain in 11 （44%）, weight loss in 10 （40%）, and 3 cases had no symptoms. The imaging features consisted of pancreatic enlargement, especially in the head of pancreas （18 cases）, strictures of main pancreatic duct and intrapancreatic bile duct. Massive lymphocytes and plasma cells infiltration in pancreatic tissues were showed on pathology, as well as parenchymal fibrosis. Twenty-three patients were misdiagnosed as pancreaticobiliary malignancy, and 21 patients underwent exploratory laparotomy, theremaining 4 patients dramatically responded to steroid therapy. No pancreatic cancer occurred during a mean 46-mo follow-up period. CONCLUSION： AIP patients always are subjected to mistaken diagnosis of pancreatic cancer and an unnecessary surgical exploration, due to its similarity in clinical features with pancreatic cancer. The differential diagnosis with high index of suspicion of AIP would improve the diagnostic accuracy for AIR

Hepatectomy for hepatocellular carcinoma in the era of liver transplantation

The aim of management of hepatocellular carcinoma(HCC)is to improve the prognosis of the patients by radical resection and preserve remnant liver function.Although liver transplantation is associated with a lower tumor recurrence rate,this benefit is counteracted by long-term complications.Therefore,hepatectomy could be the first choice of treatment in selected patients with HCC.However,the higher frequency of tumor recurrence and the lower rate of resectability after hepatectomy for HCC led to an unsatisfactory prognosis.New strategies are required to improve the long-term outcome of HCC after hepatectomy.In this paper,we introduce some strategies to increase the low rate of resectability and reduce the high rate of tumor recurrence.Some aggressive treatments for tumor recurrence to extend long-term survival are also involved.We believe that hepatectomy combined with other therapies,such as portal vein embolization,transarterial chemoembolization,radioembolization,antiviral treatment,radiofrequency ablation and salvage transplantation,is a promising treatment modality for HCC and may improve survival greatly.

Traditional surgical planning of liver surgery is modified by 3D interactive quantitative surgical planning approach： a single-center experience with 305 patients

BACKGROUND： Decision making and surgical planning are to achieve the precise balance of maximal removal of target lesion, maximal sparing of functional liver remnant volume, and minimal surgical invasiveness and therefore, crucial in liver surgery. The aim of this prospective study was to validate the accuracy and predictability of 3D interactive quantitative surgical planning approach （IQSP）, and to evaluate the impact of IQSP on traditional surgical plans based on 2D images. METHODS： A total of 305 consecutive patients undergoing hepatectomy were included in this study. Surgical plans were created by traditional 2D approach using picture archiving and communication system （PACS） and 3D approach using IQSP respectively by two groups of physicians who did not know the surgical plans of the other group. The two surgical plans were submitted to the chief surgeon for selection before operation. The specimens were weighed. The two surgical plans were compared and analyzed retrospectively based on the operation results. RESULTS： The two surgical plans were successfully developed in all 305 patients and all the 3D IQSP surgical plans were selected as the final decision. Total 278 patients successfully underwent surgery, including 147 uncomplex hepatectomy and 131 complex hepatectomy. Twenty-seven patients were withdrawn from hepatectomy. In the uncomplex group, the two surgical plans were the same in all 147 patients and no statistically significant difference was found among 2D calcu- lated resection volume （2D-RV）, 3D IQSP calculated resection volume （IQSP-RV） and the specimen volume. In the complex group, the two surgical plans were different in 49 patients （49/131, 37.4%）. According to the significance of differences, the 49 different patients were classified into three grades. No statistically significant difference was found between IQSP-RV and specimen volume. The coincidence rate of territory analy- sis of IQSP with operation was 92.1% （93/101） for 101 patients of anatomic hepatectomy. CONCLUSIONS： The accuracy and predictability of 3D IQSP were validated. Compared with traditional surgical planning, 3D IQSP can provide more quantitative information of anatomic structure. With the assistance of 3D IQSP, traditional surgical plans were modified to be more radical and safe.

Incidence of port-site metastasis after undergoing robotic surgery for biliary malignancies

AIM： To investigate the incidence of clinically detected port-site metastasis （PSM） in patients who underwent robotic surgery for biliary malignancies. METHODS： Using a prospective database, the patients undergoing fully robotic surgery for biliary malignan- cies between January 2009 and January 2011 were in- cluded. Records of patients with confirmed malignancy were reviewed for clinicopathological data and informa- tion about PSM. RESULTS： Sixty-four patients with biliary tract cancers underwent robotic surgery, and sixty patients met the inclusion criteria. The median age was 67 year （range： 40-85 year）. During a median 15-mo follow-up period, two female patients were detected solitary PSM after robotic surgery. The incidence of PSM was 3.3%. Pa- tient 1 underwent robotic anatomatic left hemihepa- tectomy and extraction of biliary tumor thrombi for an Klatskin tumor. She had a subcutaneous mass located at the right lateral abdominal wall near a trocar scar. Patient 2 underwent robotic pancreaticoduodenectomy for distal biliary cancer. She had two metachronous subcutaneous mass situated at the right lateral abdomi- nal wall under a same trocar scar at 7 and 26 mo. The pathology of the excised PSM masses confirmed meta- static biliary adenocarcinoma. CONCLUSION： The incidence of PSIVls after robotic surgery for biliary malignancies is relatively low, and biliary cancer can be an indication of robotic surgery.

Efficiency and safety of radiofrequency-assisted hepatectomy for hepatocellular carcinoma with cirrhosis:A single-center retrospective cohort study

AIM: To assess the efficiency and safety of radiofrequencyassisted hepatectomy in patients with hepatocellular carcinoma(HCC) and cirrhosis.METHODS: From January 2010 to December 2013, 179 patients with HCC and cirrhosis were recruited for this retrospective study. Of these, 100 patients who received radiofrequency-assisted hepatectomy(RF+ group) were compared to 79 patients who had hepatectomy without ablation(RF- group). The primary endpoint was intraoperative blood loss. The secondary endpoints included liver function, postoperative complications, mortality, and duration of hospital stay.RESULTS: The characteristics of the two groups were closely matched. The Pringle maneuver was not used in the RF+ group. There was significantly less median intraoperative blood loss in the RF+ group(300 vs 400 m L, P = 0.01). On postoperative days(POD) 1 and 5, median alanine aminotransferase was significantly higher in the RF+ group than in the RF- group(POD 1: 348.5 vs 245.5, P = 0.01; POD 5: 112 vs 82.5, P = 0.00), but there was no significant difference between the two groups on POD 3(260 vs 220, P = 0.24). The median AST was significantly higher in the RF+ group on POD 1(446 vs 268, P = 0.00), but there was no significant difference between the two groups on POD 3 and 5(POD 3: 129.5 vs 125, P = 0.65; POD 5: 52.5vs 50, P = 0.10). Overall, the rate of postoperative complications was roughly the same in these two groups(28.0% vs 17.7%, P = 0.11) except that post hepatectomy liver failure was far more common in the RF+ group than in the RF- group(6% vs 0%, P = 0.04).CONCLUSION: Radiofrequency-assisted hepatectomy can reduce intraoperative blood loss during liver resection effectively. However, this method should be used with caution in patients with concomitant cirrhosis because it may cause severe liver damage and liver failure.

Inhalation of hydrogen gas reduces liver injury during major hepatotectomy in swine

AIM： To study the effect of H2 gas on liver injury in massive hepatectomy using the Intermittent Pringle maneuver in swine. METHODS： Male Bama pigs （n = 14） treated with ketamine hydrochloride and Sumianxin Ⅱ as induc- tion drugs followed by inhalation anesthesia with 2% isoflurane, underwent 70% hepatotectomy with loss of bleeding less than 50 mL, and with hepatic pedicle occlusion for 20 min, were divided into two groups： Hydrogen-group （n = 7）, the pigs with inhalation of 2% hydrogen by the tracheal intubation during major hepa- totectomy; Contrast-group （n= 7）, underwent 70% hepatotectomy without inhalation of hydrogen. Hemo- dynamic changes and plasma concentrations of alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, hyaluronic acid （HA）, tumor necrosis factor-α （TNF-α）, interleukin-6 （IL-6）, and malondialdehyde （MDA） in liver tissue were measured at pre-operation, post-hepatotectomy （PH） 1 h and 3 h. The apoptosis and proliferating cell nuclear antigen （PCNA） expres- sion in liver remnant were evaluated at PH 3 h. Then we compared the two groups by these marks to evalu- ate the effect of the hydrogen in the liver injury during major hepatotectomy with the Pringle Maneuver in the swine. RESULTS： There were no significant differences in body weight, blood loss and removal liver weight be- tween the two groups. There was no significant differ- ence in changes of portal vein pressure between two groups at pre-operation, PH 30 min, but in hydrogen gas treated-group it slightly decrease and lower than its in Contrast-group at PH 3 h, although there were no significant difference （P = 0.655）. ALT and AST in Hydrogen-group was significantly lower comparing to Contrast-group （P = 0.036, P = 0.011, vs P = 0.032, P = 0.013） at PH 1 h and 3 h, although the two groups all increased. The MDA level increased between the two group at PH i h and 3 h. In the hydrogen gas treated- group, the MDA level was not significantly significant at pre-operation and significantly low at PH 1 h and 3 h comparing to Contrast-group （P = 0.0005, P = 0.0004）. In Hydrogen-group, the HA level was also significantly low to Contrast-group （P = 0.0005, P = 0.0005） al- though the two groups all increased at PH 1 h and 3 h. The expression of cluster of differentiation molecule 31 molecules Hydrogen-group was low to Contrast-group. However, PCNA index （%） was not statistically signifi- cant between the two groups （P = 0.802）. Micropho- tometric evaluation of apoptotic index （AI） in terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-stained tissue after hepatotectomy for 3h, the AI% level in the hydrogen was significantly low to Contrast-group （P = 0.012）. There were no significant difference between Hydrogen-group and Contrast- group at pre-operation （P = 0.653, P = 0.423）, but after massive hepatotectomy, the TNF-α and IL-6 levels increase, and its in Hydrogen-group was significantly low compared with Contrast-group （P = 0.022, P = 0.013, vs P = 0.016, P= 0.012）, respectively. Hydro- gen-gas inhalation reduce levels of these markers and relieved morphological liver injury and apoptosis.CONCLUSION： H2 gas attenuates markedly ischemia and portal hyperperfusion injury in pigs with massive hepatotectomy, possibly by the reduction of inflamma- tion and oxidative stress, maybe a potential agent for treatment in clinic.

Ex vivo liver resection followed by autotransplantation in radical resection of gastric cancer liver metastases:A case report

BACKGROUND Radical resection of gastric cancer liver metastases(GCLM)can increase the 5-year survival rate of GCLM patients.However,patients may lose the theoretical feasibility of surgery due to the critical location of liver metastasis in some cases.CASE SUMMARY A 29-year-old woman had a chief complaint of chronic abdominal pain for 1 year.Abdominal computed tomography and magnetic resonance imaging examinations suggested a mass of unknown pathological nature located between the first and second hila and the margin of the lower segment of the right lobe of the liver.The anterior wall of the gastric antrum was unevenly thickened.The diagnosis of(gastric antrum)intramucosal well-differentiated adenocarcinoma was histopathologically confirmed by puncture biopsy with gastroscopy guidance.She underwent radical resection(excision of both gastric tumors and ex vivo liver resection followed by autotransplantation simultaneously)followed by XELOX adjuvant chemotherapy.Without serious postoperative complications,the patient was successfully discharged on the 20th day after the operation.Pathological examination of the excised specimen indicated that gastrectomy with D2 lymph node dissection for primary gastric tumors and R0 resection for liver metastases were achieved.The resected mass was confirmed to be poorly differentiated gastric carcinoma(hepatoid adenocarcinoma with neuroendocrine differentiation)with liver metastases in segments VIII.No recurrence or metastasis within the liver was found during a 7.5-year follow-up review that began 1 mo after surgery.CONCLUSION Application of ex vivo liver resection followed by autotransplantation in radical resection for GCLM can help selected patients with intrahepatic metastases located in complex sites obtain a favorable clinical outcome.

Outcomes of liver transplantation for end-stage biliary disease: A comparative study with end-stage liver disease

AIM: To evaluate the outcomes of patients with endstage biliary disease(ESBD) who underwent liver transplantation, to define the concept of ESBD, the criteria for patient selection and the optimal operation for decision-making.METHODS: Between June 2002 and June 2014, 43 patients with ESBD from two Chinese organ transplantation centres were evaluated for liver transplantation. The causes of liver disease were primary biliary cirrhosis(n = 8), cholelithiasis(n = 8), congenital biliary atresia(n = 2), graft-related cholangiopathy(n = 18), Caroli's disease(n = 2), iatrogenic bile duct injury(n = 2), primary sclerosing cholangitis(n = 1), intrahepatic bile duct paucity(n = 1) and Alagille's syndrome(n = 1). The patients with ESBD were compared with an end-stage liver disease(ESLD) case control group during the same period, and the potential prognostic values of multiple demographic and clinical variables were assessed. The examined variables included recipient age, sex, pre-transplant clinical status, pre-transplant laboratory values, operation condition and postoperative complications, as well as patient and allograft survival rates. Survival analysis was performed using Kaplan-Meier curves, and the rates were compared using log-rank tests. All variables identified by univariate analysis with P values < 0.100 were subjected to multivariate analysis. A Cox proportional hazard regression model was used to determine the effect of the study variables on outcomes in the study group.RESULTS: Patients in the ESBD group had lower model for end-stage liver disease(MELD)/paediatric end-stage liver disease(PELD) scores and a higher frequency of previous abdominal surgery compared to patients in the ESLD group(19.2 ± 6.6 vs 22.0 ± 6.5, P = 0.023 and 1.8 ± 1.3 vs 0.1 ± 0.2, P = 0.000). Moreover, theoperation time and the time spent in intensive care were significantly higher in the ESBD group than in the ESLD group(527.4 ± 98.8 vs 443.0 ± 101.0, P = 0.000, and 12.74 ± 6.6 vs 10.0 ± 7.5, P = 0.000). The patient survival rate in the ESBD group was not significantly different from that of the ESBD group at 1, 3 and 5 years(ESBD: 90.7%, 88.4%, 79.4% vs ESLD: 84.9%, 80.92%, 79.0%, χ2 = 0.194, P = 0.660). The graftsurvival rates were also similar between the two groups at 1, 3 and 5 years(ESBD: 90.7%, 85.2%, 72.7% vs ESLD: 84.9%, 81.0%, 77.5%, χ2 = 0.003, P = 0.958). Univariate analysis identified MELD/PELD score(HR = 1.213, 95%CI: 1.081-1.362, P = 0.001) and bleeding volume(HR = 0.103, 95%CI: 0.020-0.538, P = 0.007) as significant factors affecting the outcomes of patients in the ESBD group. However, multivariate analysis revealed that MELD/PELD score(HR = 1.132, 95%CI: 1.005-1.275, P = 0.041) was the only negative factor that was associated with short survival time.CONCLUSION: MELD/PELD criteria do not adequately measure the clinical characteristics and staging of ESBD. The allocation system based on MELD/PELD criteria should be re-evaluated for patients with ESBD.

Dual targeting of Polo-like kinase 1 and baculoviral inhibitor of apoptosis repeat-containing 5 in TP53-mutated hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC),often diagnosed at advanced stages without curative therapies,is the fifth most common malignant cancer and the second leading cause of cancer-related mortality.Polo-like kinase 1(PLK1)is activated in the late G2 phase of the cell cycle and is required for entry to mitosis.Interestingly,PLK1 is overexpressed in many HCC patients and is highly associated with poor clinical outcome.Baculoviral inhibitor of apoptosis repeatcontaining 5(BIRC5)is also highly overexpressed in HCC and plays key roles in this malignancy.AIM To determine the expression patterns of PLK1 and BIRC5,as well as their correlation with p53 mutation status and patient clinical outcome.METHODS The expression patterns of PLK1 and BIRC5,and their correlation with p53 mutation status or patient clinical outcome were analyzed using a TCGA HCC dataset.Cell viability,cell apoptosis,and cell cycle arrest assays were conducted to investigate the efficacy of the PLK1 inhibitors volasertib and GSK461364 and the BIRC5 inhibitor YM155,alone or in combination.The in vivo efficacy of volasertib and YM155,alone or in combination,was assessed in p53-mutated Huh7-derived xenograft models in immune-deficient NSIG mice.RESULTS Our bioinformatics analysis using a TCGA HCC dataset revealed that PLK1 and BIRC5 were overexpressed in the same patient subset and their expression was highly correlated.The overexpression of both PLK1 and BIRC5 was more frequently detected in HCC with p53 mutations.High PLK1 or BIRC5 expression significantly correlated with poor clinical outcome.PLK1 inhibitors(volasertib and GSK461364)or a BIRC5 inhibitor(YM155)selectively targeted Huh7 cells with mutated p53,but not HepG2 cells with wild-type p53.The combination treatment of volasertib and YM155 synergistically inhibited the viability of Huh7 cells via apoptotic pathway.The efficacy of volasertib and YM155,alone or in combination,was validated in vivo in a Huh7-derived xenograft model.CONCLUSION PLK1 and BIRC5 are highly co-expressed in p53-mutated HCC and inhibition of both PLK1 and BIRC5 synergistically compromises the viability of p53-mutated HCC cells in vitro and in vivo.

Effect of histone deacetylase inhibitor on proliferation of biliary tract cancer cell lines

AIM: To explore the effect of histone deacetylase inhibitor, trichostatin A (TSA) on the growth of biliary tract cancer cell lines (gallbladder carcinoma cell line and cholangiocarcinoma cell line) in vivo and in vitro, and to investigate the perspective of histone deacetylase inhibitor in its clinical application. METHODS: The survival rates of gallbladder carcinoma cell line (Mz-ChA-l cell line) and cholangiocarcinoma cell lines (QBC939, KMBC and OZ cell lines) treated with various doses of TSA were detected by methylthiazoy tetrazolium (MTT) assay. A nude mouse model of transplanted gallbladder carcinoma (Mz-ChA-l cell line) was successfully established, and changes in the growth of transplanted tumor after treated with TSA were measured. RESULTS: TSA could inhibit the proliferation of gallbladder carcinoma cell line (Mz-ChA-l cell line) and cholangiocarcinoma cell lines (QBC939, KMBC and OZ cell lines) in a dose-dependent manner. After the nude mouse model of transplanted gallbladder carcinoma (Mz- ChA-l cell line) was successfully established, the growth of cancer was inhibited in the model after treated with TSA. CONCLUSION: TSA can inhibit the growth of cholangiocarcinoma and gallbladder carcinoma cell lines in vitro and in vivo.

Mitofusin-2 mediated mitochondrial Ca2+ uptake 1/2 induced liver injury in rat remote ischemic perconditioning liver transplantation and alpha mouse liver-12 hypoxia cell line models

AIM To investigate the protective mechanism of mitofusin-2 (Mfn2) in rat remote ischemic perconditioning (RIC) models and revalidate it in alpha mouse liver-12 (AML-12) hypoxia cell lines. METHODS Sprague-Dawley rats were divided into three groups (n = 6 each): sham, orthotopic liver transplantation and RIC. After operation, blood samples were collected to test alanine aminotransferase and aspartate aminotransferase. The liver lobes were harvested for histopathological examination, western blotting (WB) and quantitative real-time (qRT)-PCR. AML-12 cell lines were then subjected to normal culture, anoxic incubator tank culture (hypoxia) and anoxic incubator tank culture with Mfn2 knockdown (hypoxia + Si), and data of qRT-PCR, WB, mitochondrial membrane potential (Delta psi m), apoptosis, endoplasmic reticulum Ca2+ concentrations and mitochondrial Ca2+ concentrations were collected. RESULTS Both sham and normal culture groups showed no injury during the experiment. The RIC group showed amelioration of liver function compared with the orthotopic liver transplantation group (P < 0.05). qRTPCR and WB confirmed that Mfn2-mitochondrial Ca2+ uptake 1/2 (MICUs) axis was changed (P < 0.005). In AML-12 cell lines, compared with the hypoxia group, the hypoxia + Si group attenuated the collapse of..m and apoptosis (P < 0.005). The endoplasmic reticulum Ca2+ decrease and mitochondrial Ca2+ overloading observed in the hypoxia group were also attenuated in the hypoxia + Si group (P < 0.005). Finally, qRT-PCR and WB confirmed the Mfn2-MICUs axis change in all the groups (P < 0.005). CONCLUSION Mfn2 participates in liver injury in rat RIC models and AML-12 hypoxia cell lines by regulating the MICUs pathway.

Negative impact of hepatitis B surface seroclearance on prognosis of hepatitis B-related primary liver cancer

AIM To assess the impact of hepatitis B surface(HBs Ag) seroclearance on survival outcomes in hepatitis B-related primary liver cancer.METHODS Information from patients with hepatitis B-related liver cancer admitted in our hospital from 2008-2017 was retrieved. Cases diagnosed with HBs Ag(-) and HBc Ab(+) liver cancer were included in the HBs Ag seroclearance(SC) group. HBs Ag(+) liver cancer patients strictly matched for liver cancer stage(AJCC staging system, 8 th edition), Child-Pugh score, and first diagnosis/treatment method(surgery, ablation and TACE) were assigned to the HBsA g non-seroclearance(NSC) group. Then, clinical, pathological and survival data in both groups were assessed.RESULTS The SC and NSC groups comprised of 72 and 216 patients, respectively. Patient age(P < 0.001) and platelet count(P = 0.001) in the SC group were significantly higher than those of the NSC group. SC group patients who underwent surgery had more intrahepatic cholangiocarcinoma(ICC) and combined HCC-CC(CHC) cases than the NSC group, but no significant differences in tumor cell differentiation and history of liver cirrhosis were found between the two groups. The numbers of interventional treatments were similar in both groups(4.57 vs 5.07, P > 0.05). Overall survival was lower in the SC group than the NSC group(P = 0.019), with 1-,3-, and 5-year survival rates of 82.1% vs 85.1%, 43.2%vs 56.8%, and 27.0% vs 45.2%, respectively. Survival of patients with AJCC stage Ⅰ disease in the SC group was lower than that of the NSC group(P = 0.029).CONCLUSION Seroclearance in patients with hepatitis B-related primary liver cancer has protective effects with respect to tumorigenesis, cirrhosis, and portal hypertension but confers worse prognosis, which may be due to the frequent occurrence of highly malignant ICC and CHC.

Staged management of Budd-Chiari syndrome caused by co-obstruction of the inferior vena cava and main hepatic veins

BACKGROUND: Collateralized intraand extra-hepatic routes in patients with Budd-Chiari syndrome (BCS) were important. This study aimed to investigate the feasibility and clinical outcomes of the staged management of BCS based on the degree of compensation provided by intraor extra-hepatic collateral circulations. METHODS: A total of 103 adult patients with BCS caused by co-obstruction of the inferior vena cava (IVC) and main hepatic veins (MHVs) between March 2001 and October 2009 were enrolled in this study. Based on the pathological classification and degree of hemodynamic compensation by collateral circulations, treatment priority for IVC hypertension was determined in the first-stage treatment. Patients were deemed eligible for second-stage treatment when the first-stage treatment failed to relieve. RESULTS: Imaging results revealed that most patients had collateral circulations to different extents. Based on the degree of compensation provided by these collateral circulations, 74 patients underwent single-stage treatment for IVC hypertension, i.e., radiologic intervention (RI) for 61 patients and surgical procedures (SPs) for 13. One patient was treated for portal hypertension. Twenty-nine patients underwent second-stage treatment (25 underwent RI and SP, and 4 only SP). The general morbidity and mortality after all procedures were 8.3% and 1.5%, respectively. After a median follow-up of 35 months, 4 patients underwent second-stage treatment and 7 underwent recanalization of the IVC/MHVs. Two patients died of hepatocellular carcinoma and 1 died of graft obstruction. CONCLUSION: Staged management produces excellent outcomes for patients with BCS caused by co-obstruction of the IVC and MHVs.