Routine utilization of machine perfusion in liver transplantation:Ready for prime time?

The last decade has been notable for increasing high-quality research and dramatic improvement in outcomes with dynamic liver preservation.Robust evidence from numerous randomized controlled trials has been pooled by meta-analyses,providing the highest available evidence on the protective effect of machine perfusion(MP)over static cold storage in liver transplantation(LT).Based on a protective effect with less complications and improved graft survival,the field has seen a paradigm shift in organ preservation.This editorial focuses on the role of MP in LT and how it could become the new“gold standard”.Strong collaborative efforts are needed to explore its effects on long-term outcomes.

Risk factors for postoperative pancreatic fistula: Analysis of 539 successive cases of pancreaticoduodenectomy

AIM To analyze the risk factors for pancreatic fistula after pancreaticoduodenectomy.METHODS We conducted a retrospective analysis of 539 successive cases of pancreaticoduodenectomy performed at our hospital from March 2012 to October 2015. Pancreatic fistula was diagnosed in strict accordance with the definition of pancreatic fistula from the International Study Group on Pancreatic Fistula. The risk factors for pancreatic fistula were analyzed by univariate analysis and multivariate logistic regression analysis.RESULTS A total of 269(49.9%) cases of pancreatic fistula occurred after pancreaticoduodenectomy,including 71(13.17%) cases of grade A pancreatic fistula,178(33.02%) cases of grade B,and 20(3.71%) cases of grade C. Univariate analysis showed no significant correlation between postoperative pancreatic fistula(POPF) and the following factors: age,hypertension,alcohol consumption,smoking,history of upper abdominal surgery,preoperative jaundice management,preoperative bilirubin,preoperative albumin,pancreatic duct drainage,intraoperative blood loss,operative time,intraoperative blood transfusion,Braun anastomosis,and pancreaticoduodenectomy(with or without pylorus preservation). Conversely,a significant correlation was observed between POPF and the following factors: gender(male vs female: 54.23% vs 42.35%,P = 0.008),diabetes(non-diabetic vs diabetic: 51.61% vs 39.19%,P = 0.047),body mass index(BMI)(≤ 25 vs > 25: 46.94% vs 57.82%,P = 0.024),blood glucose level(≤ 6.0 mmol/L vs > 6.0 mmol/L: 54.75% vs 41.14%,P = 0.002),pancreaticojejunal anastomosis technique(pancreatic duct-jejunum double-layer mucosa-to-mucosa pancreaticojejunal anastomosis vs pancreatic-jejunum single-layer mucosa-tomucosa anastomosis: 57.54% vs 35.46%,P = 0.000),diameter of the pancreatic duct(≤ 3 mm vs > 3 mm: 57.81% vs 38.36%,P = 0.000),and pancreatic texture(soft vs hard: 56.72% vs 29.93%,P = 0.000). Multivariate logistic regression analysis showed that gender(male),BMI > 25,pancreatic duct-jejunum double-layer mucosa-to-mucosa pancreaticojejunal anastomosis,pancreatic duct diameter ≤ 3 mm,and soft pancreas were risk factors for pancreatic fistula after pancreaticoduodenectomy.CONCLUSION Gender(male),BMI > 25,pancreatic duct-jejunum double-layer mucosa-to-mucosa pancreaticojejunal anastomosis,pancreatic duct diameter ≤ 3 mm,and soft pancreas were risk factors for pancreatic fistula after pancreaticoduodenectomy.

Application of nucleoside analogues to liver transplant recipients with hepatitis B

Hepatitis B is a common yet serious infectious disease of the liver, affecting millions of people worldwide. Liver transplantation is the only possible treatment for those who advance to end-stage liver disease. Donors positive for hepatitis B virus(HBV) core antibody(HBc Ab) have previously been considered unsuitable for transplants. However, those who test negative for the more serious hepatitis B surface antigen can now be used as liver donors, thereby reducing organ shortages. Remarkable improvements have been made in the treatment against HBV, most notably with the development of nucleoside analogues(NAs), which markedly lessen cirrhosis and reduce post-transplantation HBV recurrence. However, HBV recurrence still occurs in many patients following liver transplantation due to the development of drug resistance and poor compliance with therapy. Optimized prophylactic treatment with appropriate NA usage is crucial prior to liver transplantation, and undetectable HBV DNA at the time of transplantation should be achieved. NA-based and hepatitis B immune globulin-based treatment regimens can differ between patients depending on the patients' condition, virus status, and presence of drug resistance. This review focuses on the current progress in applying NAs during the perioperative period of liver transplantation and the prophylactic strategies using NAs to prevent de novo HBV infection in recipients of HBc Ab-positive liver grafts.

PET/CT联合应用对胆囊癌和胆管癌分期及治疗的影响

Background/Aims: (1) To evaluate the diagnostic value of integrated positron emission and computed tomography (PET/CT) in comparison with contrast-enhanced CT (ceCT) to detect biliary tract tumors and associated distant and regional lymph node metastases and (2) to evaluate the impact of PET/CT on therapy management. Methods: From January 2001 to March 2005, each patient who was treated for a malignancy of the biliary tract underwent PET/CT examination in addition to the standard work-up imaging. Data were prospectively collected and analyzed in comparison with ceCT. Results: Sixty-one patients with malignancies of the biliary tract were included into the study. Diagnosis was proven in all patients either by histology or cytology. PET/CT detected all gallbladder cancers (n = 14). PET/CT and ceCT provided a comparable accuracy for the primary intra-(n = 14) and extra-hepatic cholangiocarcinomas (n = 33). All distant metastases (12/12) were detected by PET/CT, but only 3/12 by ceCT (p < 0.001). Regional lymph node metastases were detected by PET/CT and ceCT in only 12%vs. 24%. PET/CT findings resulted in a change of management in 17%of patients deemed resectable after standard work-up. Conclusions: PET/CT is particularly valuable in detecting unsuspected distant metastases which are not diagnosed by standard imaging. Thus, PET/CT staging has an important impact on selection of adequate therapy.

Loss of LAT1 sex-dependently delays recovery after caerulein-induced acute pancreatitis

BACKGROUND The expression of amino acid transporters is known to vary during acute pancreatitis(AP)except for LAT1(slc7a5),the expression of which remains stable.LAT1 supports cell growth by importing leucine and thereby stimulates mammalian target of rapamycin(mTOR)activity,a phenomenon often observed in cancer cells.The mechanisms by which LAT1 influences physiological and pathophysiological processes and affects disease progression in the pancreas are not yet known.AIM To evaluate the role of LAT1 in the development of and recovery from AP.METHODS AP was induced with caerulein(cae)injections in female and male mice expressing LAT1 or after its knockout(LAT1 Cre/LoxP).The development of the initial AP injury and its recovery were followed for seven days after cae injections by daily measuring body weight,assessing microscopical tissue architecture,mRNA and protein expression,protein synthesis,and enzyme activity levels,as well as by testing the recruitment of immune cells by FACS and ELISA.RESULTS The initial injury,evaluated by measurements of plasma amylase,lipase,and trypsin activity,as well as the gene expression of dedifferentiation markers,did not differ between the groups.However,early metabolic adaptations that support regeneration at later stages were blunted in LAT1 knockout mice.Especially in females,we observed less mTOR reactivation and dysfunctional autophagy.The later regeneration phase was clearly delayed in female LAT1 knockout mice,which did not regain normal expression of the pancreas-specific differentiation markers recombining binding protein suppressor of hairless-like protein(rbpjl)and basic helixloop-helix family member A15(mist1).Amylase mRNA and protein levels remained lower,and,strikingly,female LAT1 knockout mice presented signs of fibrosis lasting until day seven.In contrast,pancreas morphology had returned to normal in wild-type littermates.CONCLUSION LAT1 supports the regeneration of acinar cells after AP.Female mice lacking LAT1 exhibited more pronounced alterations than male mice,indicating a sexual dimorphism of amino acid metabolism.

An RNA-RNA crosstalk network involving HMGB1 and RICTOR facilitates hepatocellular carcinoma tumorigenesis by promoting glutamine metabolism and impedes immunotherapy by PD-L1+ exosomes activity

Hepatocellular carcinoma(HCC)is the global leading cause of cancer-related deaths due to the deficiency of targets for precision therapy.A new modality of epigenetic regulation has emerged involving RNA-RNA crosstalk networks where two or more competing endogenous RNAs(ceRNAs)bind to the same microRNAs.However,the contribution of such mechanisms in HCC has not been well studied.Herein,potential HMGB1-driven RNA-RNA crosstalk networks were evaluated at different HCC stages,identifying the mT0RC2 component RICTOR as a potential HMGB1 ceRNA in HBV^(+)early stage HCC.Indeed,elevated HMGB1 mRNA was found to promote the expressio n of RICTOR mRNA through competitively bin ding with the miR-200 family,especially miR-429.Functio nal assays emplo ying overexpressi on or in terference strategies dem on strated that the HMGB1 and RICTOR 3zuntra nslated regions(UTR)epigenetically promoted the malignant proliferation,self-renewal,and tumorigenesis in HCC cells.Intriguingly,in terference agai nst HMGB1 and RICTOR in HCC cells promoted a stron ger an ti-PD-L1 immuno therapy resp on se,which appeared to associate with the production of PD-L1^(+)exosomes.Mechanistically,the HMGB1-driven RNA-RNA crosstalk network facilitated HCC cell glutamine metabolism via dual mechanisms,activating a positive feedback loop involving mT0RC2-AKT-C-MYC to upregulate glutamine synthetase(GS)expression,and inducing mTORCI signaling to derepress SIRT4 on glutamate dehydrogenase(GDH).Meanwhile,this crosstalk network could impede the efficacy of immunotherapy through mTORCI-P70S6K dependent PD-L1 production and PD-L1^(+)exosomes activity.In conclusion,our study highlights the non-coding regulatory role of HMGB1 with implicatio ns for RNA-based therapeutic targeting together with a predictio n of an ti-PD-L1 immuno therapy in HCC.

The portal-umbilical-iliac-systemic venous shunt in liver cirrhosis

A 45-year-old man with 8-year history of hepatitis B virus related liver cirrhosis presented to the hospital.Physical examination revealed jaundice,severe ascites,umbilical hernia,and caput medusae.Laboratory studies showed a total bilirubin level of 4.14 mg per deciliter(normal range,0 to 1.52),a serum creatinine level of 0.92 mg per deciliter(normal range,0.64 to 1.09).

Acquired coarctation of abdominal aorta by hydatid disease

A 45-year-old woman presented to the hospital with severe back pain,inability to stand,and increased blood pressure for 4 months.She had been diagnosed with hepatic hydatid disease 4 years ago but refused any treatment.Physical examination revealed an upper limb blood pressure of 199/104 mmHg,compared to the lower limb’s 113/80 mmHg.CT scans discovered a large hilar mass involved in the abdominal aorta(Panel 1A),pathologic fractures of the T12-L2 vertebras(Panel 1B),and the coarctation of abdominal aorta at the L1 vertebra level(Panel 1C).The patient was treated with Urapidil and Nifedipine for hypertension and Albendazole for hydatid disease.After the blood pressure was controlled at 150/100 mmHg,the patient underwent laminectomy and fusion.Pathological examination confirmed alveolar echinococcosis(AE).The patient was able to walk 3 months after the surgery but died 1 year after the presentation due to disease progression.

The evolution of anatomical hepatectomy:Past,present,and future

The liver contains a complex structure of blood vessels and bile ducts,and the vascular structure is highly variable.The anatomical segmentation of the liver is still controversial,and the Couinaud segmentation method based on the portal vein is more widely used in clinical practice.The treatment of liver tumors and other lesions is closely related to the liver anatomy.The mechanism of liver tumor invasion and metastasis is complex,and it is currently believed that tumor invasion mainly spreads along the portal vein.Anatomic liver resection is an important surgical method for liver diseases,especially liver tumors.This article reviews the vascular structure of the liver,the development of anatomical hepatectomy,blood flow control,surgical planning,intraoperative navigation,minimally invasive surgery,and precise hepatectomy.Anatomic liver resection is a part of precision liver surgery,which is becoming increasingly more precise in terms of surgical evaluation,surgical planning,and surgical operation.New technologies will facilitate precision surgery with less trauma and greater benefits for patients.With the development and advancement of technology,image-based surgical planning and intraoperative surgical navigation will become more widely used in precision liver surgery.