AIM: To study the role of autophagy and the relationship between retinoic acid receptor α(RARα) and autophagy in liver ischemia and reperfusion(IR) injury.METHODS: All-trans retinoic acid(ATRA) was ...administered to mice for two weeks before operation. Reverse transcription-polymerase chain reaction and Western blot were used to detect the expression levels of related factors. To demonstrate the role of RARα,LE540,a RARα inhibitor,was used to treat hepatocytes injured by H2O2 in vitro.RESULTS: ATRA pretreatment noticeably diminished levels of serum alanine aminotransferase and as-partate aminotransferase as well as the degree of histopathological changes. Apoptosis was also inhibited,whereas autophagy was promoted. In vitro,RARα was inhibited by LE540,which resulted in decreased autophagy and increased apoptosis. Similarly,the expression of Foxo3 a and p-Akt was downregulated,but Foxo1 expression was upregulated.CONCLUSION: This research provides evidence that ATRA can protect the liver from IR injury by promoting autophagy,which is dependent on Foxo3/p-Akt/Foxo1 signaling.
Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies in China. Most HCC patients are first diagnosed at an advanced stage, and systemic treatments are the mainstay of ...treatment. Summary: In recent years, immune checkpoint inhibitors have made a breakthrough in the systemic treatment of middle-advanced HCC, breaking the single therapeutic pattern of molecular-targeted agents. To better guide the clinical treatment for effective and safe use of immunotherapeutic drugs, the Chinese Association of Liver Cancer and Chinese Medical Doctor Association has gathered multidisciplinary experts and scholars in relevant fields to formulate the “Chinese Clinical Expert Consensus on Immunotherapy for Hepatocellular Carcinoma (2021)” based on current clinical studies and clinical medication experience for reference in China. Key Messages: The consensus contained 17 recommendations, including the preferred regimen for first- and second-line immunotherapy, evaluation and monitoring before/during/after treatment, management of complications, precautions for special patients, and potential population for immunotherapy.
The progress toward clinical translation of imaging biomarkers for mass-forming intrahepatic cholangiocarcinoma (MICC) is slower than anticipated. Questions remain on the biologic behavior underlying ...imaging traits. We developed and validated imaging-based prognostic systems for resected MICCs with an appraisal of tumor immune microenvironment (TIME) underpinning patient-specific imaging traits.
Between January 2009 and December 2019, a total of 322 patients who underwent dynamic CT/MRI and curative-intent resection for MICC at three hepatobiliary institutions were retrospectively recruited, divided into training (n=193) and validation (n=129) datasets. Two radiological and clinical scoring (RACS) systems, one integrating preoperative and one integrating pre-and postoperative variables, were developed using Cox regression analysis. We then prospectively analyzed the TIME of tissue samples from 20 patients who met study criteria from January 2021 to December 2021 using multiplexed immunofluorescence.
Pre-and postoperative MICC-RACS systems built on carbohydrate antigen 19-9, albumin, tumor number, radiological/pathological nodal status, pathological necrosis and three radiological traits (arterial enhancement pattern, tumor boundary and capsular retraction), demonstrated good performance in predicting disease-specific (C-statistic＞0.80) and disease-free (C-statistic＞0.75) survival that outperformed rival models and staging systems across study cohorts (P＜0.05 for all). Patients with MICC-RACS score of 0-2 (low-risk), 3-5 (medium-risk) and ≥6 (high-risk) had incrementally worse prognosis after surgery. Significant differences in spatial distribution and infiltration level of immune cells were identified between arterial enhancement patterns. Enhanced infiltration of immunosuppressive Tregs and M2-like macrophages at invasive margin were noted in tumors with distinct boundary and capsular retraction, respectively.
Our MICC-RACS systems are simple but powerful prognostic tools that may facilitate the understanding of spatially distinct TIMEs and patient-tailored immunotherapy approach.
The progress toward clinical translation of imaging biomarkers for mass-forming intrahepatic cholangiocarcinoma (MICC) is slower than anticipated. Questions remain on the biologic behavior of MICC underlying imaging traits. In this study, we proposed novel and easy-to-use tools, built on radiological and clinical features, that demonstrated good performance in predicting the prognosis either before or after surgery and outperformed rival models/systems across major imaging modalities. The characteristic radiological traits integrated into prognostic systems (arterial enhancement pattern, tumor boundary and capsular retraction) were highly correlated with heterogeneous tumor-immune microenvironments, thereby renovating treatment paradigms for this difficult-to-treat disease.
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●We proposed novel and simple but powerful prognostic tools for MICC.●MICC-RACS systems can predict the prognosis either before or after surgery.●MICC-RACS systems outperform rival models and staging systems.●Radiological traits integrated into systems are highly correlated with TIMEs.●MICC-RACS systems may facilitate patient-tailored immunotherapy approach.
BACKGROUND： It is well-known that steatotic liver is more susceptible to ischemia-reperfusion （I/R） injury during liver transplantation, liver resection and other liver surgeries. The increasing ...incidence of non-alcoholic fatty liver disease （NAFLD） decreases the availability of liver donors. Although steatotic liver is now accepted as a source of liver for trans- plantation, NAFLD exacerbates the liver injury after liver surgery. The present study was to investigate the protective role of ankaflavin in steatotic liver I/R injury.
AIM:To investigate the effects of N-acetylcysteine(NAC) on endoplasmic reticulum(ER) stress and tissue injury during liver ischemia reperfusion injury(IRI).METHODS:Mice were injected with NAC(300 ...mg/kg) intraperitoneally 2 h before ischemia.Real-time polymerase chain reaction and western blotting determined ER stress molecules(GRP78,ATF4 and CHOP).To analyze the role of NAC in reactive oxygen species(ROS)-mediated ER stress and apoptosis,lactate dehydrogenase(LDH) was examined in cultured hepatocytes treated by H2O2 or thapsigargin(TG).RESULTS:NAC treatment significantly reduced the level of ROS and attenuated ROS-induced liver injury after IRI,based on glutathione,malondialdehyde,serum alanine aminotransferase levels,and histopathology.ROS-mediated ER stress was significantly inhibited in NAC-treated mice.In addition,NAC treatment significantly reduced caspase-3 activity and apoptosis after reperfusion,which correlated with the protein expression of Bcl-2 and Bcl-xl.Similarly,NAC treatment significantly inhibited LDH release from hepatocytes treated by H2O2 or TG.CONCLUSION:This study provides new evidence for the protective effects of NAC treatment on hepatocytes during IRI.Through inhibition of ROS-mediated ER stress,NAC may be critical to inhibit the ER-stressrelated apoptosis pathway.
Hemobilia is a rare biliary complication of liver transplantation.The predominant cause of hemobilia is iatrogenic,and it is often associated with traumatic operations,such as percutaneous liver ...intervention,endoscopic retrograde cholangiopancreatography,cholecystectomy,biliary tract surgery,and liver transplantation.Percutaneous transhepatic cholangiography and liver biopsy are two major causes of hemobilia in liver transplant recipients.Hemobilia may also be caused by coagulation defects.It can form intracholedochal hematomas,causing obstructive jaundice.Herein we describe a patient with an intracholedochal hematoma resulting in significant obstructive jaundice after liver transplantation for fulminant hepatic failure.Previous studies have shown that percutaneous transhepatic manipulation is a major cause of hemobilia after liver transplantation,but in our case,percutaneous transhepatic intervention was used to relieve the biliary obstruction and dissolve the biliary clot,with a good outcome.
A previous study has shown that liver or combined liver-kidney transplantation can be a valuable surgical technique for the treatment of polycystic liver disease. Herein, we present the case of a ...35-year-old woman with polycystic liver disease, who underwent orthotopic liver transplantation （OLT） on November 11, 2008. The whole-size graft was taken from a deceased donor （a 51-year-old man who died of a heart attack）. Resection in a patient with massive hepatomegaly is very difficult. Thus, after intercepting the portal hepatic vein, left hepatectomy was performed, then the vena cava was intercepted, the second and third porta hepatic isolated, and fi nally, right hepatectomy was performed. OLT was performed successfully. The recipient did well after transplantation. This case suggested that OLT is an effective therapeutic option for polycystic liver disease and left hepatectomy can be performed fi rst during OLT if the liver is over enlarged.
Gallstone ileus (GI) is characterized by occlusion of the intestinal lumen as a result of one or more gallstones. GI is a rare complication of gallstones that occurs in 1%-4% of all cases of bowel ...obstruction. The mortality associated with GI ranges between 12% and 27%. Classical findings on plain abdominal radiography include: (1) pneumobilia; (2) intestinal obstruction; (3) an aberrantly located gallstone; and (4) change of location of a previously observed stone. The optimal management of acute GI is controversial and can be: (1) enterotomy with stone extraction alone; (2) enterotomy, stone extraction, cholecystectomy and fistula closure; (3) bowel resection alone; and (4) bowel resection with fistula closure. We describe a case to highlight some of the pertinent issues involved in GI management, and propose a scheme to minimize recurrent disease and postoperative complications. We conclude that GI is a rare condition affecting mainly the older population with a female predominance. The advent of computed tomography and magnetic resonance imaging has made it easier to diagnose GI. Enterotomy with stone extraction alone remains the most common surgical method because of its low incidence of complications.
AIM：To study the effect of aprotinin used in orthotopic liver transplantation （OLT） on the intraoperative requirement for blood products and on the incidence of laparotomy for bleeding, thrombotic ...events and mortality.
METHODS： A systematic review of the literature in the electronic database Medline and the Clinic Trials Registry Database was performed. Literature that did not fit our study were excluded. Patients in the reviewed studies were divided into two groups; one group used aprotinin （aprotinin group） while the other did not （control group）. The data in the literature that fit our requirements were recorded. Weighted mean differences （WMD） in the requirements for blood products between the aprotinin group and the control group were tested using a fixed effect model. A Z test was performed to examine their reliability; the Fleiss method of fixed effect model was used to analyze data on postoperative events, and odds ratios （ORs） were tested and merged.
RESULTS： Seven citations were examined in our study. Among them, a requirement for blood products was reported in 4 studies including 321 patients, while postoperative events were reported in 5 studies including 477 patients. The requirement for red blood cells and fresh frozen plasma in the aprotinin group was statistically lower than that in the control group （WMD=-1.80 units, 95% CI,-3.38 to-0.22; WMD=-3.99 units, 95% CI,-6.47 to-1.50, respectively）. However, no significant difference was indicated in the incidence of laparotomy for bleeding, thrombotic events and mortality between the two groups. Analysis on blood loss, anaphylactic reactions and renal function was not performed in this study due to a lack of sufficient information.
CONCLUSION： Aprotinin can reduce the intraoperative requirement for blood products in OLT, and has no significant effect on the incidence of laparotomy for bleeding, thrombotic events and mortality.
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