Hepatocellular carcinoma and intrahepatic cholangiocarcinoma incidence between 2006 and 2015 in China: estimates based on data from 188 population-based cancer registries

Background:Hepatocellular carcinoma(HCC)and intrahepatic cholangiocarcinoma(ICC)are the most common subtypes of primary liver cancer,but nationwide incidence of both liver cancer subtypes have never been reported in China.We aimed to estimate the most recent incidence of HCC and ICC and temporal trends in China based on the most updated data from high qualified population-based cancer registries(covering 13.1%of the national population),in comparison to those in the United States at the same period.Methods:We used data from 188 Chinese population-based cancer registries covering 180.6 million population of China to estimate the nationwide incidence of HCC and ICC in 2015.And 22 population-based cancer registries’data were used to estimate the trends of HCC and ICC incidence from 2006 to 2015.Multiple imputation by chained equations method was used to impute liver cancer cases with unknown subtype(50.8%).We used data from 18 population-based registries from the Surveillance,Epidemiology,and End Results program to analyze incidence of HCC and ICC in the United States.Results:In China,an estimated 301,500 and 61,900 newly diagnosed HCC and ICC occurred in 2015.The overall age-standardized rates(ASRs)of HCC incidence decreased by 3.9%per year.For ICC incidence,the overall ASR was relatively stable,but increased in the population of over 65 years old.Subgroup analysis by age showed that the ASR of HCC incidence had the sharpest decline in population who were less than 14 years old and received neonatally hepatitis B virus(HBV)vaccination.In the United States,though the incidence of HCC and ICC were lower than those in China,the overall HCC and ICC incidence increased by 3.3%and 9.2%per year.Conclusions:China still faces with a heavy burden of liver cancer incidence.Our results may further support the beneficial effect of Hepatitis B vaccination on reduction of HCC incidence.Both healthy lifestyle promotion and infection control are needed for future liver cancer control and prevention for China and the United States.

A review of 2022 Chinese clinical guidelines on the management of hepatocellular carcinoma: updates and insights

Significant improvements in the management of hepatocellular carcinoma(HCC)during the past three years have urged the timely update of clinical guidelines in China.In brief,aMAP score is newly recommended as an effective risk stratification tool to predict HCC occurrence especially for non-cirrhotic patients.Biomarker-based surveillance including 7 micro-RNA panel and GALAD score are advocated to assist early diagnosis.China liver cancer(CNLC)staging system proposed in the 2017 guideline continues to be the standard model for staging with modifications in the treatment allocations.Conversion therapies using multi-modal,high intensity strategies are advocated to facilitate subsequent resection for patients with technically unresectable CNLC stage Ia,Ib,IIa HCC,or technically resectable IIb,IIIa HCC.Super-selective transcatheter arterial chemoembolization(TACE)with the assistance of Cone-Beam CT if necessary is recommended to guarantee the efficacy of TACE.Hepatic arterial infusion chemotherapy(HAIC)using oxaliplatin,fluorouracil,and leucovorin(FOLFOX)regimen alone or in combination with systemic therapy is recommended for TACE-refractory patients or for patients with locally advanced HCC.The systemic treatments for HCC have evolved considerably since atezolizumab plus bevacizumab,and suntilimab plus bevacizumab analogue showing superior survival benefit to sorafenib,and donafenib with comparable efficacy with sorafenib are added to the first-line treatments.In addition to regorafenib,apatinib,camrelizumab and tislelizumab are added as the second-line systemic therapies for patients who progressed on sorafenib.Updates in the 2022 Barcelona Clinic Liver Cancer(BCLC)guidelines and Japanese Society of Hepatology(JSH)consensus statement are also introduced and compared with the 2022 Chinese guidelines.

An international Delphi consensus statement on metabolic dysfunction-associated fatty liver disease and risk of chronic kidney disease

Background:With the rising global prevalence of fatty liver disease related to metabolic dysfunction,the association of this common liver condition with chronic kidney disease(CKD)has become increasingly evident.In 2020,the more inclusive term metabolic dysfunction-associated fatty liver disease(MAFLD)was proposed to replace the term non-alcoholic fatty liver disease(NAFLD).The observed association between MAFLD and CKD and our understanding that CKD can be a consequence of underlying metabolic dysfunction support the notion that individuals with MAFLD are at higher risk of having and developing CKD compared with those without MAFLD.However,to date,there is no appropriate guidance on CKD in individuals with MAFLD.Furthermore,there has been little attention paid to the link between MAFLD and CKD in the Nephrology community.Methods and Results:Using a Delphi-based approach,a multidisciplinary panel of 50 international experts from 26 countries reached a consensus on some of the open research questions regarding the link between MAFLD and CKD.Conclusions:This Delphi-based consensus statement provided guidance on the epidemiology,mechanisms,management and treatment of MAFLD and CKD,as well as the relationship between the severity of MAFLD and risk of CKD,which establish a framework for the early prevention and management of these two common and interconnected diseases.

Validation of the Enhanced Recovery after Surgery (ERAS) society recommendations for liver surgery: a prospective, observational study

Twenty-three recommendations were summarized by the Enhanced Recovery After Surgery(ERAS)society for liver surgery.The aim was to validate the protocol especially with regard to adherence and the impact on morbidity.Methods:Using the ERAS Interactive Audit System(EIAS),ERAS items were evaluated in patients undergoing liver resection.Over a period of 26 months,304 patients were prospectively enrolled in an observational study(DRKS00017229).Of those,51 patients(non-ERAS)were enrolled before and 253 patients(ERAS)after the implementation of the ERAS protocol.Perioperative adherence and complications were compared between the two groups.Results:Overall adherence increased from 45.2%in the non-ERAS group to 62.7%in the ERAS group(P<0.001).This was associated with significant improvements in the preoperative and postoperative phase(P<0.001),rather than in the outpatient and intraoperative phase(both P>0.05).Overall complications decreased from 41.2%(n=21)in the non-ERAS group to 26.5%(n=67)in the ERAS group(P=0.0423),which was mainly due to the reduction of grade 1-2 complications from 17.6%(n=9)to 7.6%(n=19)(P=0.0322).As for patients undergoing open surgery,implementation of ERAS lead to a reduction of overall complications in patients scheduled for minimally invasive liver surgery(MILS)(P=0.036).Conclusions:Implementation of the ERAS protocol for liver surgery according to the ERAS guidelines of the ERAS Society reduced Clavien-Dindo grade 1-2 complications particularly in patients who underwent MILS.The ERAS guidelines are beneficial for the outcome,while adherence to the various items has not yet been satisfactorily defined.

Robotic versus laparoscopic liver resection for huge (≥10 cm) liver tumors: an international multicenter propensity-score matched cohort study of 799 cases

Background:The use of laparoscopic(LLR)and robotic liver resections(RLR)has been safely performed in many institutions for liver tumours.A large scale international multicenter study would provide stronger evidence and insight into application of these techniques for huge liver tumours≥10 cm.Methods:This was a retrospective review of 971 patients who underwent LLR and RLR for huge(≥10 cm)tumors at 42 international centers between 2002-2020.Results:One hundred RLR and 699 LLR which met study criteria were included.The comparison between the 2 approaches for patients with huge tumors were performed using 1:3 propensity-score matching(PSM)(73 vs.219).Before PSM,LLR was associated with significantly increased frequency of previous abdominal surgery,malignant pathology,liver cirrhosis and increased median blood.After PSM,RLR and LLR was associated with no significant difference in key perioperative outcomes including media operation time(242 vs.290 min,P=0.286),transfusion rate rate(19.2%vs.16.9%,P=0.652),median blood loss(200 vs.300 mL,P=0.694),open conversion rate(8.2%vs.11.0%,P=0.519),morbidity(28.8%vs.21.9%,P=0.221),major morbidity(4.1%vs.9.6%,P=0.152),mortality and postoperative length of stay(6 vs.6 days,P=0.435).Conclusions:RLR and LLR can be performed safely for selected patients with huge liver tumours with excellent outcomes.There was no significant difference in perioperative outcomes after RLR or LLR.

Surgery for metastatic pancreatic neuroendocrine tumors: a narrative review

Background and Objective:Pancreatic neuroendocrine tumors(PanNETs)are derived from the islet cells of the pancreas and have been increasing in incidence.Most of these tumors are nonfunctional although some can secrete hormones and lead to hormone-specific clinical syndromes.Surgery is the mainstay of treatment for localized tumors,however,surgical resection is controversial in metastatic PanNETs.This narrative review seeks to summarize the current literature surrounding surgery,specifically in the controversial area of metastatic PanNETs,review current treatment paradigms,and understand the benefits of surgery in this group of patients.Methods:Authors searched PubMed using the terms“surgery pancreatic neuroendocrine tumor”,“metastatic neuroendocrine tumor”,and“liver debulking neuroendocrine tumor”from January 1990 to June 2022.Only English language publications were considered.Key Content and Findings:There is no consensus among the leading specialty organizations regarding surgery for metastatic PanNETs.When considering surgery for metastatic PanNETs,tumor grade and morphology,location of the primary tumor,extra-hepatic or extra-abdominal disease,as well as liver tumor burden and metastatic distribution should be considered.Because the liver is the most common site of metastasis and liver failure is the most common cause of death in patients with hepatic metastases,attention is centered here on debulking and other ablative techniques.Liver transplantation is rarely used for hepatic metastases but could be beneficial in a small subset of patients.Retrospective studies have demonstrated improvement in survival and symptoms after surgery for metastatic disease,but the lack of prospective randomized control trials significantly limits analysis of surgical benefits in patients with metastatic PanNETs.Conclusions:Surgery is the standard of care for localized PanNETs,while it remains controversial in metastatic disease.Many studies have shown a survival and symptomatic benefit to surgery and liver debulking in select groups of patients.However,most of the studies on which recommendations are based in this population are retrospective in nature and are subject to selection bias.This presents an opportunity for future investigation.

Predictors and long-term prognosis of early and late recurrence for patients undergoing hepatic resection of hepatocellular carcinoma: a large-scale multicenter study

Recurrence is common among patients undergoing hepatic resection for hepatocellular carcinoma(HCC),which greatly limits long-term survival.We aimed to identify predictors and long-term prognosis of early and late recurrence after HCC resection.Methods:Multicenter data of patients who underwent HCC resection between 2002 and 2016 were analyzed.Recurrence was divided into early(≤2 years)and late recurrence(>2 years after surgery).Predictors of early and late recurrence,and prognostic factors of post-recurrence survival(PRS)were identified by univariate and multivariate analyses.Results:Among 1,426 patients,554(38.8%)and 348(24.4%)developed early and late recurrence,respectively.Independent predictors associated with early recurrence included preoperative alpha-fetoprotein level>400μg/L,resection margin<1 cm,and tumor size>5.0 cm,multiplicity,macrovascular and microvascular invasion,and satellites of the initial tumor at the first diagnosis of HCC;independent predictors associated with late recurrence included male,cirrhosis,and tumor size>5.0 cm,multiplicity,macrovascular and microvascular invasion,and satellites of the initial tumor.Patients with early recurrence had a lower likelihood of undergoing potentially curative treatments for recurrence(37.2%vs.48.0%,P<0.001)and a worse median PRS(13.5 vs.36.6 months,P<0.001)vs.patients who had late recurrence.Multivariate analysis revealed that early recurrence and irregular postoperative surveillance were independently associated with worse PRS[hazard ratio(HR)=1.250,95%CI:1.016-1.538,P=0.035;and HR=1.983,95%CI:1.677-2.345,P<0.001].Conclusions:Predictors associated with early and late recurrence after curative resection for patients with HCC were generally same,although several did differ.Patients with late recurrence had better long-term survival than patients with early recurrence.

Wilson’s disease:practical information for general physicians

Wilson’s disease is an autosomal-recessive disorder with an ATP7B mutation that causes a functional failure of the copper-transporting protein ATP7B(1,2).As a result,unbound copper in the blood increases,and due to copper accumulation,multiple organs show various symptoms,e.g.,Kayser-Fleischer rings,acute liver failure,liver cirrhosis,liver cancer,dysarthria,tremors,character changes,renal disorders,rheumatological symptoms,endocrinopathy,heart failure,and arrhythmias(3,4).This disease afflicts approximately 1 in 40,000 people,with approximately 1 carrier for every 100 people,and early diagnosis is difficult.

Association of tumor morphology with long-term prognosis after liver resection for patients with a solitary huge hepatocellular carcinoma-a multicenter propensity score matching analysis

Background:A solitary hepatocellular carcinoma(HCC)without macrovascular invasion and distant metastasis,regardless of tumor size,is currently classified as early-stage disease by the latest Barcelona Clinic Liver Cancer(BCLC)staging system.While the preferred treatment is surgical resection,the association of tumor morphology with long-term survival outcomes after liver resection for a solitary huge HCC of≥10 cm has not been defined.Methods:Patients who underwent curative liver resection for a solitary huge HCC were identified from a multicenter database.Preoperative imaging findings were used to define spherical-or ellipsoidal-shaped lesions with smooth edges as balloon-shaped HCCs(BS-HCCs);out-of-shape lesions or lesions of any shape with matt edges were defined as non-balloon-shaped HCCs(NBS-HCCs).The two groups of patients with BS-HCCs and NBS-HCCs were matched in a 1:1 ratio using propensity score matching(PSM).Clinicopathologic characteristics,long-term overall survival(OS)and recurrence-free survival(RFS)were assessed.Results:Among patients with a solitary huge HCC,74 pairs of patients with BS-HCC and NBS-HCC were matched.Tumor pathological features including proportions of microvascular invasion,satellite nodules,and incomplete tumor encapsulation in the BS-HCC group were lower than the NBS-HCC group.At a median follow-up of 50.7 months,median OS and RFS of all patients with a solitary huge HCC after PSM were 27.8 and 10.1 months,respectively.The BS-HCC group had better median OS and RFS than the NBS-HCC group(31.9 vs.21.0 months,P=0.01;and 19.7 vs.6.4 months,P=0.015).Multivariate analyses identified BS-HCC as independently associated with better OS(HR=0.592,P=0.009)and RFS(HR=0.633,P=0.013).Conclusions:For a solitary huge HCC,preoperative imaging on tumor morphology was associated with prognosis following resection.In particular,patients with BS-HCCs had better long-term survival following liver resection versus patients with large NBS-HCCs.

Optimizing management of patients with pancreatic exocrine insufficiency

Pancreatic exocrine insufficiency(PEI)is related to decreased pancreatic enzyme availability and/or activity(1).Multiples underlying mechanisms can cause PEI,such as loss of functioning parenchyma(chronic pancreatitis,pancreatic resections,pancreatic cancer...),decreased secretion despite intact parenchyma(obstruction of the pancreatic duct,decreased endogenous stimulation,intraduodenal inactivation of pancreatic secretions),and asynchrony(gastric resections,Roux-en-Y gastric by-pass)(1).

The promise of precision medicine:how biomarkers are shaping the future of cholangiocarcinoma treatment

Cholangiocarcinoma(CCA)is the second most frequent primary malignant neoplasm of the hepatobiliary system.Unfortunately,CCA is often diagnosed at an advanced stage,when potentially curative surgical treatments are not recommended.The probability of achieving complete resection in patients who undergo surgery is about 25%(1)and even when complete tumor removal is achieved,the risk of recurrence is greater than 50%.Identification and validation of reliable biomarkers is crucial for the early detection,accurate diagnosis,appropriate staging/prognosis,therapy selection and effective monitoring of patients with biliary tract cancers(BTCs)(Figure 1).Achieving early diagnosis remains a challenge to improve survival and,although many promising biomarkers have been identified(2),to date none have reached clinical practice.

Large,multifocal or portal vein-invading hepatocellular carcinoma(HCC)downstaged by Y90 using personalized dosimetry:safety,pathological results and outcomes after surgery

Background:Transarterial radioembolization(TARE)has recently been recognized as a bridging/downstaging therapy to surgery for early hepatocellular carcinomas(HCCs)with high rates of complete pathological necrosis(CPN)on liver explants.In patients with portal vein tumoral thrombus(PVTT),multifocal or large tumors,TARE has mainly a palliative role and surgery remains controversial in this poor-prognosis population.Personalized dosimetry recently proved to outperform standard dosimetry used in prior negative Y90 randomized-controlled trials.Methods:In this retrospective study,we evaluated safety,radiological and pathological response and outcomes in HCC patients with PVTT,multifocal or large tumors,who underwent surgery after downstaging using TARE with Y90-loaded glass microspheres with personalized dosimetry.Results:Between December 2015 and October 2021,18 unresectable patients(14/18 with PVTT)had surgery(16 resections,2 liver transplantations)6.2 months(range,2-14.6 months)after a single Y90 treatment.No 90-day mortality was reported.Objective modified response criteria in solid tumors(mRECIST)response were noted in all but one patient.Complete and extensive(50-99%)necrosis was observed in 36%and 45%of tumors,respectively.The post-treatment tumor-absorbed dose significantly differed depending on the extent of pathological necrosis(P=0.045).Median overall survival and progression-free survival(PFS)were respectively of 61.8 months[95%CI:31.4 months-not reached(NR)]and 49.3 months(95%CI:14 months-NR).PFS was longer in patients with complete imaging response[median NR(none recurred or died)vs.21.5 months(95%CI:10.1 months-NR),P<0.001]and in those with complete pathological response[median NR vs.22.5 months(95%CI:10.1 months-NR),P<0.001].Conclusions:Y90 TARE using personalized dosimetry can provide high rates of imaging and pathological response in patients with PVTT,large or multifocal HCC.Subsequent surgery is safe and leads to outcomes far exceeding expectations in an otherwise poor prognosis population with no chance for cure.

Liver transplantation for non-resectable colorectal liver metastases

At present,there are no absolute practice guidelines for liver transplants in colorectal liver metastases(CRLM),and treatment protocols for unresectable CRLM are institution-specific(1).One of the first prospective studies evaluating the safety of liver transplants for CRLM was the SECA-I trial(1,2).A 5-year overall survival rate of 60% was observed in this trial,which far outperformed survival with chemotherapy alone(3).In the SECA-Ⅱ trial,enrollment was increased,and patients with better prognostic factors,including at least a 10% response to chemotherapy before the transplant,were selected.

Subharmonic scattering of ultrasound contrast agent microbubbles may be an effective and promising tool for portal vein pressure estimation

Portal hypertension(PH)is a commonly observed syndrome in patients with cirrhosis and other chronic liver diseases(1).It is closely associated with severe clinical complications,including upper gastrointestinal hemorrhage,ascites,hepatic encephalopathy,and liver failure(2-6).Portal vein pressure(PVP)is a prognostic indicator for patients with cirrhosis,and PH is a contraindication for hepatectomy(7,8).Currently,the gold standard for assessing PVP is the measurement of PVP gradient[hepatic venous pressure gradient(HVPG)],which is indirectly determined by placing a catheter in the hepatic vein(3).

A narrative review of the current and future role of robotic surgery in liver surgery and transplantation

Background:Minimally invasive surgery(MIS)is the technique of choice in selected patients for the treatment of liver tumors.The robotic approach is considered today the natural evolution of MIS.The application of the robotic technique in liver transplantation(LT)has been recently evaluated,especially in the living donation.The aim of this paper is to review the current role of the MIS and robotic donor hepatectomy in the literature and to evaluate the possible future implication in the transplant field.Methods:We conducted a narrative review using PubMed and Google Scholar for reports published so far,using the following keywords:minimally invasive liver surgery,laparoscopic liver surgery,robotic liver surgery,robotic living donation,laparoscopic donor hepatectomy and robotic donor hepatectomy.Results:Several advantages have been claimed in favor of robotic surgery:three-dimensional(3-D)imaging with stable and high-definition view;a more rapid learning curve than the laparoscopic one;the lack of hand tremors and the freedom of movements.Compared to open surgery,the benefits showed in the studies evaluating the robotic approach in the living donation are:less postoperative pain,the shorter period before returning to normal activity despite sustaining longer operation time.Furthermore,the 3-D and magnification view makes the technique excellent in distinguishing the right plane of transection,vascular and biliary anatomy,associated with high precision of the movements and a better bleeding control(essential for donor safety)and lower rate of vascular injury.Conclusions:The current literature does not fully support the superiority of the robotic approach versus laparoscopic or open method in living donor hepatectomy.Robotic donor hepatectomy performed by teams with high expertise and in properly selected living donors is safe and feasible.However,further data are necessary to evaluate properly the role of robotic surgery in the field of living donation.

The difficulty of medical decision-making:should patients be involved?

Introduction The success or failure of treatment has long been attributed to the doctors alone,but the role of patients in the medical decision-making(MDM)process has often been ignored.As medical development and health needs increase,the desire of patients to participate in MDM continues to grow.This raises the question:should patients be involved in such a highly professional medical activity?How can their involvement bring better clinical benefits?

Is HPB robotic-assisted surgery an evolution or a revolution in laparoscopy?

Robotic-assisted surgery technology demonstrates a new prospect for surgery.Its advantages are particularly prominent in specific surgery divisions or for specific surgical procedures,which has set off a new wave of surgical technology following laparoscopic surgery.Looking back at the history of surgical development over the past century,there have been many technological waves,some of which have become classics and standards,some of which are constantly evolving,and some of which have been gradually abandoned in practice.In the context of the increasingly mature and accurate laparoscopic surgery,which has become a standard operation of many types of surgery,the government,medical institutions and surgeons should carefully consider the role and future development of robotic-assisted surgery.

Impact of pure laparoscopic surgery on bile duct division of living donor left lateral section procurement

Background:Although laparoscopic living donor left lateral section liver procurements represents an established and safe procedure,there remains much discussion on this topic.In particular,the issue of whether laparoscopic living donor liver procurement increases the difficulty of the surgery and potential complications for recipients continue to confound experts in this field.Methods:In this report,data from 180 cases of living donor left lateral section liver transplantation patients were analyzed retrospectively.Of these 180 cases,106 grafts were procured by open surgery and 74 by pure laparoscopic surgery.Results:While surgery durations and blood loss were decreased in donors from the laparoscopic surgery group,increased biliary openings of grafts and relatively high peak aspartate aminotransferase(AST)levels were present in both donors and recipients with this procedure.Conclusions:Laparoscopic living donor left lateral section liver procurement represents a safe and effective procedure for both donors and recipients.However,laparoscopic surgery can more frequently lead to multiple biliary tracts in the graft and its impact on the prognosis of recipients remains uncertain.Use of routine X-ray based intraoperative cholangiography may help to reduce this problem.

Foregut bypass vs.restrictive bariatric procedures for nonalcoholic fatty liver disease:a meta-analysis of 3,355 individuals

Background:Bariatric surgery represents an important treatment option for severely obese patients with nonalcoholic fatty liver disease(NAFLD).However,there remains inadequate data regarding the effects of different bariatric procedures on various NAFLD parameters,especially for histological outcomes.Thus,this meta-analysis aimed to compare the effects of restrictive bariatric procedures and foregut bypass on the metabolic,biochemical,and histological parameters for patients with NAFLD.Methods:Medline and Embase were searched for articles relating to bariatric procedures and NAFLD.Pairwise meta-analysis was conducted to compare efficacy of bariatric procedures pre-vs.post-procedure with subgroup analysis to further compare restrictive against foregut bypass procedures.Results:Thirty-one articles involving 3,355 patients who underwent restrictive bariatric procedures(n=1,460)and foregut bypass(n=1,895)were included.Both foregut bypass(P<0.01)and restrictive procedures(P=0.03)significantly increased odds of fibrosis resolution.Compared to restrictive procedures,foregut bypass resulted in a borderline non-significant decrease in fibrosis score(P=0.06)and significantly lower steatosis score(P<0.001).For metabolic parameters,foregut bypass significantly lowered body mass index(P=0.003)and low-density lipoprotein(P=0.008)compared to restrictive procedures.No significant differences were observed between both procedures for aspartate aminotransferase(P=0.17)and alkaline phosphatase(P=0.61).However,foregut bypass resulted in significantly lower gamma-glutamyl transferase than restrictive procedures(P=0.01)while restrictive procedures resulted in significantly lower alanine transaminase than foregut bypass(P=0.02).Conclusions:The significant histological and metabolic advantages and comparable improvements in biochemical outcomes support the choice of foregut bypass over restrictive bariatric procedures in NAFLD management.

AASLD practice guidance on drug,herbal,and dietary supplement-induced liver injury:also useful for hepatobiliary surgeons

Drug-induced liver injury(DILI)is a term used to describe an unexpected liver reaction to drugs,but also to herbal products and dietary supplements(HDS).In the current therapeutic armamentarium,only a small number of available drugs are still capable of causing liver damage in overdose.These include,in addition to paracetamol-the prototypical example of this group-niacin(now rarely used to treat hypercholesterolaemia),intravenous methotrexate and probably ketamine(an intravenous hypnotic used in critically ill patients for rapid sequence induction)(1).