Comprehensive review of hepatocellular carcinoma with portal vein tumor thrombus:State of art and future perspectives

Background:Despite advances in the diagnosis of patients with hepatocellular carcinoma(HCC),70%-80%of patients are diagnosed with advanced stage disease.Portal vein tumor thrombus(PVTT)is among the most ominous signs of advanced stage disease and has been associated with poor survival if untreated.Data sources:A systematic search of MEDLINE(PubMed),Embase,Cochrane Library and Database for Systematic Reviews(CDSR),Google Scholar,and National Institute for Health and Clinical Excellence(NICE)databases until December 2022 was conducted using free text and MeSH terms:hepatocellular carcinoma,portal vein tumor thrombus,portal vein thrombosis,vascular invasion,liver and/or hepatic resection,liver transplantation,and systematic review.Results:Centers of surgical excellence have reported promising results related to the individualized surgical management of portal thrombus versus arterial chemoembolization or systemic chemotherapy.Critical elements to the individualized surgical management of HCC and portal thrombus include precise classification of the portal vein tumor thrombus,accurate identification of the subgroups of patients who may benefit from resection,as well as meticulous surgical technique.This review addressed five specific areas:(a)formation of PVTT;(b)classifications of PVTT;(c)controversies related to clinical guidelines;(d)surgical treatments versus non-surgical approaches;and(e)characterization of surgical techniques correlated with classifications of PVTT.Conclusions:Current evidence from Chinese and Japanese high-volume centers demonstrated that patients with HCC and associated PVTT can be managed with surgical resection with acceptable results.

Simultaneous portal and hepatic vein embolization is better than portal embolization or ALPPS for hypertrophy of future liver remnant before major hepatectomy: A systematic review and network meta-analysis

Background:Post-hepatectomy liver failure(PHLF)is the Achilles’heel of hepatic resection for colorectal liver metastases.The most commonly used procedure to generate hypertrophy of the functional liver remnant(FLR)is portal vein embolization(PVE),which does not always lead to successful hypertrophy.Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)has been proposed to overcome the limitations of PVE.Liver venous deprivation(LVD),a technique that includes simultaneous portal and hepatic vein embolization,has also been proposed as an alternative to ALPPS.The present study aimed to conduct a systematic review as the first network meta-analysis to compare the efficacy,effectiveness,and safety of the three regenerative techniques.Data sources:A systematic search for literature was conducted using the electronic databases Embase,PubMed(MEDLINE),Google Scholar and Cochrane.Results:The time to operation was significantly shorter in the ALPPS cohort than in the PVE and LVD cohorts by 27 and 22 days,respectively.Intraoperative parameters of blood loss and the Pringle maneuver demonstrated non-significant differences between the PVE and LVD cohorts.There was evidence of a significantly higher FLR hypertrophy rate in the ALPPS cohort when compared to the PVE cohort,but non-significant differences were observed when compared to the LVD cohort.Notably,the LVD cohort demonstrated a significantly better FLR/body weight(BW)ratio compared to both the ALPPS and PVE cohorts.Both the PVE and LVD cohorts demonstrated significantly lower major morbidity rates compared to the ALPPS cohort.The LVD cohort also demonstrated a significantly lower 90-day mortality rate compared to both the PVE and ALPPS cohorts.Conclusions:LVD in adequately selected patients may induce adequate and profound FLR hypertrophy before major hepatectomy.Present evidence demonstrated significantly lower major morbidity and mortality rates in the LVD cohort than in the ALPPS and PVE cohorts.

Managements of recurrent hepatocellular carcinoma after liver transplantation: A systematic review

AIM: To investigate the efficacy(survival) and safety of treatments for recurrent hepatocellular carcinoma(HCC) in liver transplantation(LT) patients.METHODS: Literature search was performed on available online databases without a time limit until January 2015. Clinical studies describing survival after HCC recurrence in LT patients were retrieved for a fulltext evaluation. A total of 61 studies were selected: 13 case reports, 41 retrospective case series, and 7 retrospective comparative studies.RESULTS: Based on all included studies, the mean HCC recurrence rate was 16% of all LTs for HCC. A total of 1021 LT patients experienced HCC recurrence. The median time from LT to HCC recurrence was 13 mo(range 2-132 mo). The majority of patients(67%) presented with HCC extra-hepatic recurrences, involving lung, bone, adrenal gland, peritoneal lymph nodes, and rarely the brain. Overall survival after HCC recurrence was 12.97 mo. Surgical resection of localized HCC recurrence and Sorafenib for controlling systemic spread of HCC recurrence were associated with the higher survival rates(42 and 18 mo, res-pectively). However, Sorafenib, especially when combined with m TOR, was frequently associated with severe side effects that required dose reduction or discontinuation CONCLUSION: Management of recurrent HCC in LT patients is challenging and associated with poor prognosis independently of the type of treatment.

International consensus statement on robotic hepatectomy surgery in 2018

The robotic surgical system has been applied in liver surgery. However,controversies concerns exist regarding a variety of factors including the safety,feasibility, efficacy, and cost-effectiveness of robotic surgery. To promote the development of robotic hepatectomy, this study aimed to evaluate the current status of robotic hepatectomy and provide sixty experts' consensus and recommendations to promote its development. Based on the World Health Organization Handbook for Guideline Development, a Consensus Steering Group and a Consensus Development Group were established to determine the topics, prepare evidence-based documents, and generate recommendations. The GRADE Grid method and Delphi vote were used to formulate the recommendations. A total of 22 topics were prepared analyzed and widely discussed during the 4 meetings. Based on the published articles and expert panel opinion, 7 recommendations were generated by the GRADE method using an evidence-based method, which focused on the safety, feasibility, indication,techniques and cost-effectiveness of hepatectomy. Given that the current evidences were low to very low as evaluated by the GRADE method, further randomized-controlled trials are needed in the future to validate these recommendations.

Ciliated hepatic foregut cyst with high intra-cystic carbohydrate antigen 19-9 level

A ciliated hepatic foregut cyst(CHFC)is a rare foregut developmental malformation usually diagnosed in adulthood.Five percent of reported cases of CHFC transform into squamous cell carcinoma.We report the presentation,evaluation,and surgical management of a symptomatic 45-year-old male found to have a 6.2 cm CHFC.Contrast tomography-guided fine-needle aspirationdemonstrated columnar,ciliated epithelium consistent with the histologic diagnosis of CHFC.The intracystic levels of carbohydrate antigen(CA)19-9 and carcinoembryonic antigen(CEA)were extremely high(978118U/m L and 973μg/L,respectively).Histologically,the wall of the cyst showed characteristic pseudopapillae lined with a ciliated stratified columnar epithelium,underlying smooth muscle,an outer fibrous layer and no atypia.Immunohistochemistry for CA19-9 and CEA was positive.This is the first case report of a CHFC in which levels of CA 19-9 and CEA were measured.Our findings suggest that a large sized multilocular cyst and elevated cyst CA19-9 and CEA levels do not exclude a CHFC from consideration in the diagnosis.CHFCs should be included in the differential diagnosis of hepatic lesions.Accurate diagnosis of a CHFC is necessary given its potential for malignant transformation,and surgical excision is recommended.

比较在之间开并且为憩室炎的 Hartmanns 过程的 laparoscopic 颠倒

AIM: To compare the open and laparoscopic Hartmann’s reversal in patients first treated for complicated diverticulitis.METHODS: Forty-six consecutive patients with diverticular disease were included in this retrospective,singlecenter study of a prospectively maintained colorectal surgery database.All patients underwent conventional Hartmann’s procedures for acute complicated diverticulitis.Other indications for Hartmann’s procedures were excluded.Patients underwent open(OHR) or laparoscopic Hartmann’s reversal(LHR) between 2000 and 2010,and received the same pre-and post-operative protocols of cares.Operative variables,length of stay,short-(at 1 mo) and long-term(at 1 and 3 years) postoperative complications,and surgery-related costs were compared between groups.RESULTS: The OHR group consisted of 18 patients(13 males,mean age ± SD,61.4 ± 12.8 years),and the LHR group comprised 28 patients(16 males,mean age 54.9 ± 14.4 years).The mean operative time and the estimated blood loss were higher in the OHR group(235.8 ± 43.6 min vs 171.1 ± 27.4 min;and 301.1 ± 54.6 mL vs 225 ± 38.6 mL respectively,P = 0.001).Bowel function returned in an average of 4.3 ± 1.7 d in the OHR group,and 3 ± 1.3 d in the LHR group(P = 0.01).The length of hospital stay was significantly longer in the OHR group(11.2 ± 5.3 d vs 6.7 ± 1.9 d,P 【 0.001).The 1 mo complication rate was 33.3% in the OHR(6 wound infections) and 3.6% in the LHR group(1 hemorrhage)(P = 0.004).At 12 mo,the complication rate remained significantly higher in the OHR group(27.8% vs 10.7%,P = 0.03).The anastomotic leak and mortality rates were nil.At 3 years,no patient required re-intervention for surgical complications.The OHR procedure had significantly higher costs(+56%) compared to the LHR procedure,when combining the surgery-related costs and the length of hospital stay.CONCLUSION: LHR appears to be a safe and feasible procedure that is associated with reduced hospitality stays,complication rates,and costs compared to OHR.

Impact of previous cyst-enterostomy on patients' outcome following resection of bile duct cysts

AIM:To analyze the impact of previous cyst-enterostomy of patients underwent congenital bile duct cysts(BDC) resection.METHODS:A multicenter European retrospective study between 1974 and 2011 were conducted by the French Surgical Association.Only Todani subtypes I and IVb were included.Diagnostic imaging studies and operative and pathology reports underwent central revision.Patients with and without a previous history of cystenterostomy(CE) were compared.RESULTS:Among 243 patients with Todani types I and IVb BDC,16 had undergone previous CE(6.5%).Patients with a prior history of CE experienced a greater incidence of preoperative cholangitis(75% vs 22.9%,P < 0.0001),had more complicated presentations(75% vs 40.5%,P = 0.007),and were more likely to have synchronous biliary cancer(31.3% vs 6.2%,P = 0.004) than patients without a prior CE.Overall morbidity(75% vs 33.5%;P < 0.0008),severe complications(43.8% vs 11.9%;P = 0.0026) and reoperation rates(37.5% vs 8.8%;P = 0.0032) were also significantly greater in patients with previous CE,and their Mayo Risk Score,during a median follow-up of 37.5 mo(range:4-372 mo) indicated significantly more patients with fair and poor results(46.1% vs 15.6%;P = 0.0136).CONCLUSION:This is the large series to show that previous CE is associated with poorer short-and longterm results after Todani types I and IVb BDC resection.

Delayed and short course of rapamycin prevents organ rejection after allogeneic liver transplantation in rats

AIM To test whether a delayed and short course of rapamycin would induce immunosuppressive effects following allogeneic orthotopic liver transplantation(OLT) in rats.METHODS Allogeneic OLTs were performed using Dark Agoutilivers transplanted into Lewis recipients, and syngeneic OLTs were performed using the Lewis rat strain. Rapamycin(1 mg/kg per day) was administered by gavage from day 4 to day 11 post-transplantation. Lymphocyte cellular compartments were analyzed by flow cytometry in draining lymph nodes, non-draining lymph nodes and the spleen at days 11 and 42 in rapamycin-treated rats, untreated control rats and syngeneic grafted rats. Skin grafts from Dark agouti or from F344 RT were performed at day 30 on liver grafted rats treated with rapamycin.RESULTS An 8-d course of rapamycin treatment initiated 4 d following transplantation resulted in the survival of grafted rats for more than 100 d. In contrast, untreated rats died of liver failure within 13 to 21 d. The analysis of the cellular compartment revealed an increase in two cellular subpopulations, specifically myeloid-derived suppressor cells(MDSCs) and CD8+CD45RClow T cells, without major modifications in the regulatory T cell(Treg) compartment in treated rats in the early stages after grafting. We evaluated the ability of treated rats to reject third-party allogeneic skin grafts to confirm their immune competence. In contrast, when skin was collected from rats syngeneic to the grafted liver, it was not rejected.CONCLUSION Our results demonstrate that short and delayed rapamycin treatment allows for tolerance in allogeneic OLT. The results also allowed for the identification of the mechanisms of tolerance induced by rapamycin by identifying MDSCs and CD8+CD45RClow T cells as associated with the state of tolerance.

Associating liver partition and portal vein ligation or combined transarterial chemo-embolisation and portal vein embolisation for staged hepatectomy for HBV-related hepatocellular carcinoma

Many patients with hepatocellular carcinoma are diagnosed with large tumours at an advanced stage.In addition,conditions such as liver fibrosis,cirrhosis,portal hypertension,viral load,and portal vein thrombosis due to either non-neoplastic or portal vein tumour thrombus limit the indications for surgical management to a select subset of individuals(1).

Improving actual survival after hepatectomy for intrahepatic cholangiocarcinoma—still a long way to go

Complete resection stands as the only potentially curative treatment.Being often late diagnosed,vascular and biliary structures are frequently involved owing to centrally located and/or large lesions at the time of diagnosis.Consequently,complete resection can require complex hepatectomy often on diseased liver,associated with important risks of mortality and morbidity while benefits in terms of prolonged survival remain often uncertain.To date,only one large series investigating actual long-term survival after curative-intent hepatectomy reported an actual 5-year OS of 13%(1).Indeed,around two thirds of patients experience recurrence,mostly to the liver,and eventually die of disease recurrence(2).These observations suggest first that patient selection for resection might be inadequate.Second,surgery alone seems not able to provide sufficient disease control.For instance,recurrence is frequently observed even with early tumours classified AJCC 8th Edition stage IA disease resulting in an estimated 5-year disease specific survival nearing 60%only.

Systemic review of the robustness of randomized controlled trials for the treatment of cholangiocarcinoma in three domains: survival-inferred fragility index, restricted mean survival time, and the spin effect

Background:The vast majority of patients with cholangiocarcinoma(CC)have advanced disease at diagnosis and are candidates for palliative treatment only.The robustness of the randomized controlled trials regarding the treatment of CC are assessed.Methods:A systematic review of all randomized control trials(RCT)of treatments for both intra-and extrahepatic CC between 2010 and 2020 was performed.The survival-inferred fragility index(SIFI;the minimum number of reassignments of the best survivors between arms that would overturn the statistical outcomes)was calculated.In addition,the gain,or loss,in survival in RCTs was evaluated by the restricted mean survival time(RMST)difference.Finally,the level of spin i.e.,misrepresentation of study outcomes,was measured in inconclusive studies to assess distorted reporting strategies.Results:Out of 6,167 studies retrieved,11 could be retained for full text revision(7 with both intra-and extrahepatic CC,3 with peri-hilar CC,and 1 with peri-hilar or distal CC).Only 3 studies included resected patients(2 with both intra-and extrahepatic CC and 1 with peri-hilar or distal CC).Nine studies investigated systemic chemotherapy(including 3 after surgical resection),one study evaluated photodynamic therapy,and another investigated the use of an endoscopically inserted stent in the biliary tract.The median SIFI was−2[interquartile range(IQR):−6.25,−0.25]across all studies.Overall,the median RMST difference was 0.56 months(IQR:0.10,0.95).Finally,for inconclusive studies,the level of spin was high,moderate,and low in respectively 12.5%,25%,and 62.5% of the studies.Conclusions:RCTs of CC showed a low degree of robustness with a frequent proportion of associated spin.

The quest for optimal and reliable guidelines based on robust evidence for the treatment of cholangiocarcinoma

In 1991,Gordon H.Guyatt described the evidence-based medicine(EBM)as“a focus on educating front-line clinicians in assessing the credibility of research evidence,understanding the results of clinical studies,and determining how best to apply the results to their everyday practice”(1).In 2010,Graham et al.defined clinical guidelines as“statements that include recommendations intended to optimize patient care that are informed by a systematic review of the evidence and an assessment of the benefits and harms of alternative care options”(2).Since 2010,the number of clinical guidelines increased exponentially,and the query on PubMed with the term“new guidelines”produces 59,773 results.