Liver resection is justified for multinodular hepatocellular carcinoma in selected patients with cirrhosis: A multicenter analysis of 1,066 patients

BackgroundThe role of liver resection for multinodular (≥3 nodules) hepatocellular carcinoma (HCC) remains unclear, especially among patients with severe underlying liver disease. We sought to evaluate surgical outcomes among patients with cirrhosis and multinodular HCC undergoing liver resection.MethodsUsing a multicenter database, outcomes among cirrhotic patients who underwent curative-intent resection of HCC were examined stratified according to the presence or absence of multinodular disease. Perioperative mortality and morbidity, as well as overall survival (OS) and recurrence-free survival (RFS) were compared between the two groups.ResultsAmong 1066 cirrhotic patients, 906 (85.0%) had single- or double-nodular HCC (the non-multinodular group), while 160 (15.0%) had multinodular HCC (the multinodular group). There were no differences in postoperative 30-day mortality and morbidity among non-multinodular versus multinodular patients (1.8% vs. 1.9%, P = 0.923, and 36.0% vs. 39.4%, P = 0.411, respectively). In contrast, 5-year OS and RFS of multinodular patients were worse compared with non-multinodular patients (34.6% vs. 58.2%, and 24.7% vs. 44.5%, both P < 0.001). On multivariable analyses, tumor numbers ≥5, total tumor diameter ≥8 cm and microvascular invasion were independent risk factors for decreased OS and RFS after resection of multinodular HCC in cirrhotic patients.ConclusionsLiver resection can be safely performed for multinodular HCC in the setting of cirrhosis with an overall 5-year survival of 34.6%. Tumor number ≥5, total tumor diameter ≥8 cm and microvascular invasion were independently associated with decreased OS and RFS after resection in cirrhotic patients with multinodular HCC.     

Real-world role of performance status in surgical resection for hepatocellular carcinoma: A multicenter study

BackgroundThe Barcelona Clinic Liver Cancer (BCLC) categorizes a patient with performance status (PS)-1 as advanced stage of hepatocellular carcinoma (HCC) and surgical resection is not recommended. In real-world clinical practice, PS-1 is often not a contraindication to surgery for HCC. The aim of current study was to define the impact of PS on the surgical outcomes of patients undergoing liver resection for HCC.Methods1,531 consecutive patients who underwent a curative-intent resection of HCC between 2005 and 2015 were identified using a multi-institutional database. After categorizing patients into PS-0 (n = 836) versus PS-1 (n = 695), perioperative mortality and morbidity, overall survival (OS) and recurrence-free survival (RFS) were compared.ResultsOverall perioperative mortality and major morbidity among patients with PS-0 (n = 836) and PS-1 (n = 695) were similar (1.4% vs. 1.6%, P = 0.525 and 9.7% vs. 10.2%, P = 0.732, respectively). In contrast, median OS and RFS was worse among patients who had PS-1 versus PS-0 (34.0 vs. 107.6 months, and 20.5 vs. 60.6 months, both P < 0.001, respectively). On multivariable Cox-regression analyses, PS-1 was independently associated with worse OS (HR: 1.301, 95% CI: 1.111–1.523, P < 0.001) and RFS (HR: 1.184, 95% CI: 1.034–1.358, P = 0.007).ConclusionsPatients with PS-1 versus PS-0 had comparable perioperative outcomes. However, patients with PS-1 had worse long-term outcomes as PS-1 was independently associated with worse OS and RFS. Routine exclusion of HCC patients with PS-1 from surgical resection as recommended by the BCLC guidelines is not warranted.     

Transarterial chemoembolization versus best supportive care for patients with hepatocellular carcinoma with portal vein tumor thrombus：a multicenter study

BackgroundThis study aims to compare the efficacy and safety of treatment after transarterial chemoembolization(TACE) with best supportive care (BSC) in patients with hepatocellular carcinoma (HCC) with PVTT.MethodsThis retrospective study was conducted on 1,040 patients with HCC with PVTT who were treated either with TACE (n = 675) or BSC (n = 365). BSC did not include sorafenib. The two groups of patients were compared with or without propensity score matching. A subgroup analysis was subsequently performed by stratifying patients according to the stages of PVTT in the Cheng's PVTT classification.ResultsIn PVTTtypes I-III, TACE was associated with significantly better overall survival (OS) thanBSC (P < 0.05). Within each type of PVTT for patients who received TACE or BSC, OS was significantly worse in patients with type IVPVTT than in any of the other three types of PVTT (all P < 0.05). TACE was associated with better long-termOS than BSC after propensity score matching or on stratification by the PVTT types.ConclusionTACE was associated with better OS than BSC in HCC patients with PVTT types I-III but not type IV. Patients with type IV PVTT showed the worst prognosis, regardless of whether TACE or BSC was used.     

Albumin-bilirubin (ALBI) grade-based nomogram to predict tumor recurrence in patients with hepatocellular carcinoma

BackgroundTumor recurrence after curative resection is common in hepatocellular carcinoma (HCC), but large-scale long-term prediction on an individual basis has seldom been reported. We aimed to construct an albumin-bilirubin (ALBI) grade-based nomogram to predict tumor recurrence in patients with HCC undergoing surgical resection.MethodsA total 1038 patients with newly diagnosed HCC undergoing curative resection between 2002 and 2016 were enrolled. Baseline characteristics, tumor status and severity of liver functional reserve were collected. The Cox proportional hazards model was used to predict tumor recurrence and construct the nomogram. The performance of the nomogram was evaluated by the discrimination and calibration tests.ResultsAfter a mean follow up time of 30 months, 510 (49%) patients developed tumor recurrence. The cumulative recurrence-free survival at 1, 3, 5, and 10 years were 79%, 51%, 38% and 26%, respectively. In the Cox multivariate model, ALBI grade 2–3, multiple tumors, tumor size equal or large than 2 cm, serum ɑ-fetoprotein level equal or greater than 20 ng/ml and total tumor volume equal or larger than 227 cm³ were independent risk factors associated with tumor recurrence. A nomogram was constructed based on these five variables. Internal validation with 10,380 bootstrapped sample sets had a good concordance of 0.607 (95% of confidence interval: 0.587–0.627). The calibration plots for 1-, 3- and 5-year recurrence-free survival well matched the idealized 45-degree line.ConclusionsALBI is a feasible marker for tumor recurrence. This easy-to-use ALBI grade-based nomogram may predict tumor recurrence for individual HCC patient undergoing surgical resection.     

Impact of ABO-incompatibility on hepatocellular carcinoma recurrence after living donor liver transplantation

BackgroundABO-incompatible (ABO-I) living donor liver transplantation (LDLT) has been reported to have acceptable outcomes in the era of rituximab-based prophylaxis. However, the outcomes of ABO-I LDLT for hepatocellular carcinoma (HCC) remain to be elucidated. This study aimed to clarify the impact of ABO-Incompatibility on oncologic outcomes of LDLT for HCC.MethodsPatients with HCC who underwent ABO-I LDLT were randomly matched by 1:2 ratio to those who underwent ABO-compatible (ABO-C) LDLT according to propensity score. HCC recurrence and patient survival were analyzed using the Kaplan-Meier method and log-rank test.ResultsBetween January 2012 and December 2015, a total of 160 patients underwent LDLT for HCC confirmed by pathology analysis of liver explants. Thirty-nine consecutive patients underwent ABO-I LDLT for HCC, and 78 ABO-C LDLT patients were selected by propensity score matching, which made no significant difference between the two groups in baseline, perioperative, and tumor characteristics. The 1-, 3-, and 5-year recurrence-free survival rates in the ABO-I and ABO-C LDLT groups were 76.9%, 68.5%, 63.6% and 74.4%, 70.5%, 70.5%, respectively (p = 0.77). The site distribution of initial recurrence showed no significant difference between the two groups. The overall survival rates over the same period in the ABO-I and ABO-C LDLT groups were 82.1%, 73.5%, 73.5% and 92.2%, 80.3%, 80.3%, respectively (p = 0.34).ConclusionsABO-I LDLT, having no adverse impact on oncological outcomes, can be a feasible transplant option for HCC.     

Postoperative morbidity adversely impacts long-term oncologic prognosis following hepatectomy for hepatocellular carcinoma: A multicenter observational study

Background & aimsPostoperative morbidity following hepatectomy for hepatocellular carcinoma (HCC) is common and its impact on long-term oncological outcome remains unclear. This study aimed to investigate if postoperative morbidity impacts long-term survival and recurrence following hepatectomy for HCC.MethodsThe data from a multicenter Chinese database of curative-intent hepatectomy for HCC were analyzed, and independent risks of postoperative 30-day morbidity were identified. After excluding patients with postoperative early deaths (≤90 days), early (≤2 years) and late (>2 years) recurrence rates, overall survival (OS), and time-to-recurrence (TTR) were compared between patients with and without postoperative morbidity.ResultsAmong 2,161 patients eligible for the study, 758 (35.1%) had postoperative 30-day morbidity. Multivariable logistic regression analysis showed that diabetes mellitus, obesity, Child-Pugh grade B, cirrhosis, and intraoperative blood transfusion were independent risks of postoperative morbidity. The rates of early and late recurrence among patients with postoperative morbidity were higher than those without (50.7% vs. 38.8%, P < 0.001; and 41.7% vs. 34.1%, P = 0.017). Postoperative morbidity was associated with decreased OS (median: 48.1 vs. 91.6 months, P < 0.001) and TTR (median: 19.8 vs. 46.1 months; P < 0.001). After adjustment of confounding factors, multivariable Cox-regression analyses revealed that postoperative morbidity was associated with a 27.8% and 18.7% greater likelihood of mortality (hazard ratio 1.278; 95% confidence interval: 1.126–1.451; P < 0.001) and recurrence (1.187; 1.058–1.331; P = 0.004).ConclusionThis large multicenter study provides strong evidence that postoperative morbidity adversely impacts long-term oncologic prognosis after hepatectomy for HCC. The prevention and management of postoperative morbidity may be oncologically important.     

Spontaneous rupture of hepatocellular carcinoma: Optimal timing of partial hepatectomy

BackgroundPartial hepatectomy has been used to treat patients with resectable hepatocellular carcinoma (HCC) which spontaneously ruptured. It is still controversial as to whether emergency partial hepatectomy (EmPH) should be carried out at the time of rupture, or the patients should initially be managed by operative or non-operative treatment to stop the bleeding, followed by staged early or delayed partial hepatectomy when the patient's condition becomes stable.MethodsConsecutive 10-year patients with ruptured HCC managed at our center were included in this study. Patients who underwent partial hepatectomy were further subdivided into the EmPH group, the staged early partial hepatectomy (SEPH) group, and the staged delayed partial hepatectomy (SDPH) group. Univariate and multivariate analyses of factors affecting overall survival(OS) were conducted before and after propensity score matching analyses amongst the included patients. OS, postoperative mortality, recurrence free survival (RFS), and peritoneal metastatic rates were compared. The risk factors of peritoneal metastases were determined using the COX regression analysis.ResultsThe 130 patients who underwent partial hepatectomy were subdivided into the EmPH group (surgery at the time of rupture, n = 30), the SEPH group (surgery ≤ 8 days of rupture, n = 67), and the SDPH group (surgery > 8 days of rupture, n = 33). The remaining 86 patients underwent non-surgical treatment. Partial hepatectomy was an independent predictor of better OS (HR 2.792, P < 0.001). For resectable HCC, the 30-day mortality, OS, and RFS were similar between the EmPH group, and the staged partial hepatectomy (SPH) group which included the patients who underwent SEPH and SDPH. The SEPH group had significantly better OS and RFS. Multivariate COX regression analysis demonstrated that SDPH was strongly associated with postoperative peritoneal dissemination (OR 28.775, P = 0.003).ConclusionPartial hepatectomy provided significantly better survival than non-surgical treatment for patients who presented with ruptured HCC. Early partial hepatectomy within 8 days of rupture which included EmPH (carefully selected) and SEPH, resulted in significantly less patients with peritoneal dissemination and better long-term survival outcomes (especially RFS) than SDPH.     

The cost-effectiveness of TheraSphere in patients with hepatocellular carcinoma who are eligible for transarterial embolization

IntroductionThe aim of the study is to estimate the cost-effectiveness of TheraSphere against other embolic treatments in a population with early to intermediate stage hepatocellular carcinoma (HCC) who are unresectable at presentation and are eligible for transarterial embolization (TAE), conventional transarterial chemoembolization (cTACE) or drug-eluting bead TACE (DEB-TACE).Materials and methodsA Markov model was constructed using a UK National Health Service (NHS) perspective, a 20-year time horizon, and four-week cycles. The eight health states included ‘watch and wait’, ‘transplantation’ (pre-, post and post (No HCC)), ‘resection’, ‘no HCC other’, ‘pharmacological management’ and ‘death’. Clinical data were sourced from literature and expert opinion. Resource use and costs were reflective of the NHS, and benefits were quantified using Quality-Adjusted Life Years (QALYs), with utility weights sourced from literature.Comparators were TAE, cTACE and DEB-TACE. The primary output was the Incremental Cost-Effectiveness Ratio (ICER) expressed as cost per QALY gained. An ICER of under £20,000/QALY gained for an intervention is cost-effective and represents efficient use of healthcare resources. Extensive deterministic and probabilistic sensitivity analyses were undertaken.ResultsTheraSphere patients were predicted to gain 0.7 additional QALYs compared to all other treatments. The base case ICERs for TheraSphere were £17,300, £17,279 and £23,020 per QALY gained compared to TAE, cTACE and DEB-TACE, respectively. In the TheraSphere cohort, 87% more patients were predicted to achieve downstaging compared to all other treatment options.ConclusionsThis study indicates that treatment with TheraSphere is a potentially cost-effective option for patients with early to intermediate stage HCC.     

Association of primary tumor location with long-term oncological prognosis following hepatectomy for hepatocellular carcinoma:A multicenter propensity score matching analysis

PurposeThere is a striking laterality in the site of hepatocellular carcinoma (HCC), with a strong predominance for the right side; however, the impact of primary tumor location on long-term prognosis after hepatectomy of HCC remains unclear. This study aimed to investigate the effect of primary tumor location on long-term oncological prognosis after hepatectomy for HCC.Patients and methodsData of consecutive patients undergoing curative hepatectomy for HCC between 2008 and 2017 were analyzed. Overall survival (OS) and recurrence-free survival (RFS) of left-sided HCC (LS group) and right-sided HCC (RS group) were compared by using propensity score matching (PSM) analysis. COX regression analysis was performed to assess the adjusted effect of tumor location on long-term oncological prognosis.ResultsOf the 2799 included patients, 707 (25.3%) and 2092 (74.7%) were in the LS and RS groups, respectively. Using PSM analysis, 650 matched pairs of patients were created. In the PSM cohort, median OS (66.0 vs. 72.0 months, P = 0.001) and RFS (28.0 vs. 51.0 months, P < 0.001) were worse among patients in the LS group compared to individuals in the RS group. After further adjustment for other confounders using multivariable COX regression analyses, HCC located on the left side remained independently associated with worse OS and RFS.ConclusionTumors located on the left side are associated with poorer OS and RFS after hepatectomy for HCC. Careful surgical options selection and frequent follow-up to improve long-term survival may be justified for HCC patients with left-sided primary tumors.     

Comparison of anatomic and non-anatomic resections for very early-stage hepatocellular carcinoma: The importance of surgical resection margin width in non-anatomic resection

BackgroundThe superiority of anatomic resection (AR) over non-anatomic resection (NAR) for very early-stage hepatocellular carcinoma (HCC) has remained a topic of debate. Thus, this study aimed to compare the prognosis after AR and NAR for single HCC less than 2 cm in diameter.MethodsConsecutive patients with single HCC of diameter less than 2 cm who underwent curative hepatectomy between 1997 and 2017 were included in this retrospective study.ResultsIn total, 159 patients were included in this study. Of these, 52 patients underwent AR (AR group) and 107 patients underwent NAR (NAR group). No significant differences were noted in recurrence-free survival (RFS) and overall survival (OS) between the AR and NAR groups (P = 0.236 and P = 0.363, respectively). Multivariate analysis revealed that low preoperative platelet count and presence of satellite nodules were independent prognostic factors of RFS and OS. Wide surgical resection margin did not affect RFS (P = 0.692) in the AR group; however, in the NAR group, RFS was found to be higher with surgical resection margin widths ≥1 cm than with surgical resection margin widths <1 cm (P = 0.038).ConclusionsPrognosis was comparable between the NAR and AR groups for very early-stage HCC with well-preserved liver function. For better oncologic outcomes, surgeons should endeavor in keeping the surgical resection margin widths during NAR ≥1 cm.     

Long-term surgical outcomes of Non alcoholic fatty liver disease associated hepatocellular carcinoma

BackgroundThe global burden of non-alcoholic fatty liver disease (NAFLD) and NAFLD-associated hepatocellular carcinoma (HCC) is steadily rising. We pursued to investigate the results after liver resection for NAFLD-HCC versus hepatitis B virus (HBV)-HCC exploiting Kaplan Meier method, log-rank test and uni/multivariate analysis with the logistic regression models”.MethodsPatients who underwent liver resection for HCC between January 2004 and December 2018 were included. The outcomes of NAFLD-associated HCC were analyzed.ResultsThe prevalence of NAFLD-associated HCC was 8.4%. A significant number of NAFLD patients had no cirrhosis (21 patients; 38.8%). Although NAFLD patients had a significantly better 5-year survival (P = 0.033), NAFLD was not significantly associated with overall survival in multivariate analysis (P = 0.287). However, survival after 5 years declined in NAFLD patients and was similar to HBV. NAFLD was protective against systemic recurrence compared with HBV (P = 0.018), and this was confirmed in multivariate analysis (P = 0.044). Five-year systemic recurrence (P = 0.044) was significantly lower in NAFLD patients and decreased with time from surgery. Multivariate analysis revealed that anatomical liver resection was independently associated with decreased recurrence in NAFLD patients (HR = 0.337; P = 0.033).ConclusionOverall survival is similar between NAFLD-associated HCC and HBV-associated HCC. Despite there being no significant difference between liver function tests, type of surgery performed, liver cirrhosis, size of tumor, number of tumors, pathological factors like satellite nodules and Edmonson Steiner staging, NAFLD-associated HCC shows lower systemic recurrence compared to HBV-associated HCC.     

Role of stratifin (14-3-3 sigma) in adenocarcinoma of gallbladder: A novel prognostic biomarker

BackgroundGallbladder cancer (GBC) is a rare and fatal biliary tract malignancy. Genetic derangements are one of many factors that determine the prognosis of GBC. In this study, the expression of the stratifin (SFN) gene encoding 14-3-3 sigma protein, which is reported to be associated with the metastatic property of cholangiocarcinoma cells, was investigated in GBC.Material and methodsFormalin-fixed paraffin-embedded cancer (n = 37) and non-cancer control tissues (n = 14) of gallbladders from patients who underwent surgical resection from January 2006 to May 2015 were retrieved. The expression of SFN normalized with that of ACTB was determined using RT-qPCR. Multivariate analysis of factors affecting disease-free survival (DFS) and overall survival (OS) including the type of SFN expression was performed.ResultThe average expression level of SFN in cancer was higher than that in control tissues (p = 0.002). The relative SFN expression in cancer tissue was classified as overexpression (n = 14) and control level expression (n = 23) according to the receiver operating characteristic (ROC) curves for discriminating early GBC recurrence or metastasis after surgery. The SFN overexpression group was associated with lower rates of distant metastasis and early tumor recurrence following resection. The univariate analysis demonstrated factors affecting DFS, including resection margin (p < 0.001), lymphovascular invasion (p = 0.040), perineural invasion (p = 0.046), and SFN expression (p < 0.001). The multivariate analysis revealed that the resection margin (p = 0.019) and SFN expression (P = 0.040) were independent prognostic factors of DFS.ConclusionTo achieve the longest survival, margin-free resection is recommended. The overexpression of SFN in GBC is associated with better prognosis, lower rates of early cancer recurrence, and distant metastasis following resection. SFN expression might be a novel prognostic biomarker in GBC treatment. Further studies to elucidate the role of SFN might unveil its clinical benefit in cancer treatment regimens.     

Trans-arterial chemoembolization + radiofrequency ablation versus surgical resection in hepatocellular carcinoma – A meta-analysis

BackgroundHepatocellular Carcinoma (HCC) remains the third most common cause of cancer death worldwide, with countries in Asia being affected the most. The mainstay of curative therapy for early HCC is radiofrequency ablation (RFA) or surgery; either surgical resection (SR) or liver transplantation. Latest evidence however suggests that combination of TACE+ RFA may provide outcomes comparable to SR.AimTo compare oncologic outcomes and safety profile of TACE + RFA to SR alone in HCC.Materials and methodsA systematic review was conducted through Pubmed, EMBASE and Cochrane Library for literature published before April 2019. Outcomes measured were disease-free survival(DFS), overall survival(OS) and major complications. DFS was further divided into local tumour progression(LTP), intrahepatic distant recurrence(IDR) and distant metastasis(DM).ResultsEight retrospective studies and one randomized controlled trial, involving 1892 patients met eligibility criteria and were included. Unadjusted pooled analysis demonstrated no significant difference in 1-year, 3-year and 5-year OS and 1-year DFS between TACE+RFA and SR. SR had superior 3-year DFS (OR 0.78, 95% CI 0.62–0.98, p = 0.03) and 5-year DFS (OR 0.74, 95% CI 0.58–0.95, p = 0.02) compared to TACE+RFA. When analysing only the propensity matched data, the difference in 3-year DFS and 5-year DFS was not significant. TACE+RFA had a higher LTP rate (OR 2.48, 95% CI 1.05–5.86, p = 0.04) compared to SR but IDR and DM rates were not significant.Discussion and conclusionTACE+RFA offer comparable oncologic outcomes in patients with HCC as compared with SR and with added benefit of lower morbidity.     

Long-term outcomes of deceased donor liver transplantation in hepatocellular carcinoma patients with portal vein tumor thrombus: A multicenter study

BackgroundThe incidence of portal vein tumor thrombus (PVTT) has been reported to be as high as approximately 10%–40% in patients with hepatocellular carcinoma (HCC). The long-term prognosis of deceased donor liver transplantation (DDLT) in HCC patients with PVTT remains unknown.MethodsData of 961 HCC patients who underwent DDLT between 2015 and 2018 in six centers were analyzed. Based on the Milan criteria (MC) and Cheng's classification of PVTT, the patients were divided into 4 groups: within MC, beyond MC without PVTT, type 1 PVTT, and type 2 PVTT groups.Results489 (50.9%) were within the MC, 296 (30.8%) beyond the MC but without PVTT, 83 (8.6%) type 1 PVTT, and 93 (9.7%) type 2 PVTT. Kaplan-Meier analysis showed that type 1 or 2 PVTT patients with alpha-fetoprotein (AFP) ≤ 100 ng/mL had overall survival (OS) similar to that of patients within the MC (P = 0.957), and superior OS (P = 0.003 and 0.009) and recurrence-free survival (RFS) (P = 0.038 and <0.001) than those of patients beyond the MC and PVTT patients with AFP > 100 ng/mL. Multivariable Cox-regression analysis identified type 1 and 2 PVTT to be independent risk factor for RFS [hazard ratio (HR) 1.523 95% confidence interval (CI) 1.162–1.997, P = 0.002], but not for OS (HR 1.283, 95%CI 0.922–1.786, P = 0.139).ConclusionHCC patients with type 1 or 2 PVTT may be acceptable candidates for DDLT. To achieve better outcomes, preoperative AFP levels should be seriously considered when selecting patients with PVTT for DDLT.     

No touch isolation technique for the prevention of postoperative recurrence of hepatocellular carcinoma after liver transplantation-combined with trans-arterial radioembolization

IntroductionTransarterial radioembolization (TARE) is recently emerging treatment modality using radiation from Yttrium-90 through the transarterial approach. It usually is used in the intermediate stage and unresectable hepatocellular carcinoma (HCC).No touch isolation technique is a way to prevent the spread of tumors by pre-ligating the vessels around the tumor with minimal touch during surgery. We hoped that if we were to use these techniques, we would be able to control all viable tumors before liver transplantation. Then we could get better outcomes even in the advanced hepatocellular carcinoma patients.MethodsWe performed living donor liver transplantation using no touch isolation technique in the patients who had multinodular hepatocellular carcinoma and extremely high AFP, PIVKA-II level after TARE and conventional TACE.Results36 years old female patient had liver cirrhosis with hepatitis B virus infection and multiple hepatocellular carcinoma in both lobes. Hepatologist decided to do TARE and additional conventional TACE for viable tumors. After that treatment, AFP and PIVKA-II level were dramatically decreased, we decided to proceed of living donor liver transplantation because the patient's treatment response was extremely good.ConclusionsNo touch isolation technique combined with TARE for recipient hepatectomy might be helpful in advanced stage hepatocellular carcinoma patients.     

Sirolimus-based immunosuppression improves the prognosis of liver Transplantation Recipients with low TSC1/2 expression in hepatocellular carcinoma beyond the Milan Criteria

BackgroundThe use of the immunosuppressive agent sirolimus (SRL) following liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) is controversial. Sirolimus is a typical mammalian target of rapamycin (mTOR) inhibitor, and tuberous sclerosis 1-tuberous sclerosis 2 complex (TSC1/TSC2) is an important negative effector in the mTOR pathway. In this study, we investigated the effect of SRL-based immunosuppression on the prognosis of LT recipients with HCC beyond the Milan criteria based on TSC1/2 expression and explored the effect of TSC1 on HCC in vitro and in vivo.MethodsWe retrospectively analyzed 120 HCC patients who underwent LT in our hospital between January 1, 2015 and December 30, 2018. All patients had HCC beyond the Milan criteria and were divided into the SRL group (n = 50) and non-SRL group (n = 70). TSC1/2 expression levels in paraffin-embedded tissues were determined by immunohistochemistry (IHC) and then analyzed as subgroups. Overall survival (OS) and disease-free survival (DFS) were analyzed using the Kaplan-Meier method. TSC1 expression was silenced in Huh-7 and Bel-7402 cell lines for further cell function experiments.Results88.3% of patients were HBV LT recipients. The SRL group exhibited better DFS and OS compared to the non-SRL group (P = 0.02, P = 0.003). Subgroup (TSC1-based or TSC2-based) analyses revealed that patients with low TSC1 or TSC2 expression benefited from sirolimus (DFS: P = 0.046, OS: P = 0.006 for TSC1; DFS: P = 0.05, OS: P = 0.003 for TSC2) compared with patients with high expression. TSC1 knockdown in Huh-7 and Bel-7402 HCC cell lines activated the mTORC1 pathway and enhanced cell proliferation, migration and sensitivity to SRL in vitro and in vivo.ConclusionTSC1/2 expression could be used to predict the prognosis of patients with HCC beyond the Milan criteria who underwent SRL-based immunosuppression following LT. TSC1 knockdown promoted HCC malignancy and enhanced sensitivity to SRL.     

A nomogram to predict early postoperative recurrence of hepatocellular carcinoma with portal vein tumour thrombus after R0 liver resection: A large-scale,multicenter study

BackgroundPortal vein tumour thrombus (PVTT) is a significant poor prognostic factor for hepatocellular carcinoma (HCC). Patients with PVTT limited to a first-order branch or above of the main portal vein (MPV) could benefit from R0 liver resection (LR). A nomogram is needed to predict early postoperative recurrence (ER) in HCC patients with PVTT and to guide selection of these patients for adjuvant therapy to reduce postoperative recurrence risks.MethodsHCC patients with PVTT limited to a first-order branch or above of the MPV after R0 LR as an initial therapy were included. A nomogram using data from a retrospective training cohort was developed with the Cox regression model. The model was tested in a prospective internal validation cohort and three external validation cohorts.ResultsOf 979 patients, 657 developed postoperative ER (67.1%). ER occurred in 165 of 264 patients (62.5%) in the training cohort, 146 of 218 patients (70.0%) in the internal validation cohort, and 204 of 284 patients (71.8%), 77 of 113 patients (68.1%), and 65 of 100 patients (65%) in the three external validation cohorts, respectively. The nomogram included the following variables: hepatitis B surface antigen (HBsAg), PVTT, HBV DNA, satellite nodules, α-fetoprotein, and tumour diameter. The ROC were 0.836, 0.763, 0.802, 0.837, and 0.846 in predicting ER in the five respective cohorts.ConclusionA nomogram was developed and validated to predict postoperative ER in patients with HCC with PVTT after R0 LR. This nomogram could select appropriate patients with high ER risks for postoperative adjuvant therapy.     

Impact of concurrent splenectomy and esophagogastric devascularization on surgical outcomes of partial hepatectomy for hepatocellular carcinoma in patients with clinically significant portal hypertension: A multicenter propensity score matching analysis

PurposePortal hypertension due to cirrhosis is common among patients with hepatocellular carcinoma (HCC). This study aimed to compare the outcomes of partial hepatectomy in patients with HCC and clinically significant portal hypertension (CSPH) with or without concurrent splenectomy and esophagogastric devascularization (CSED).Patients and methodsFrom a multicenter database, patients with HCC and CSPH who underwent curative-intent hepatectomy were identified. Postoperative morbidity and mortality, and long-term overall survival (OS) were compared in patients with and without CSED before and after propensity score matching (PSM).ResultsOf the 358 enrolled patients, 86 patients underwent CSED. Before PSM, the postoperative 30-day morbidity and mortality rates were comparable between the CSED and non-CSED group (both P > 0.05). Using PSM, 81 pairs of patients were created. In the PSM cohort, the 5-year OS rate of the CSED group were significantly better than the non-CSED group (52.9% vs. 36.5%, P = 0.046). The former group had a significantly lower rate of variceal bleeding on follow-up (7.4% vs. 21.7%, P = 0.014). On multivariate analysis, CSED was associated with significantly better OS (HR: 0.39, P < 0.001).ConclusionHepatectomy and CSED can safely be performed in selected patients with HCC and CSPH, which could improve postoperative prognosis by preventing variceal bleeding, and prolonging long-term survival.     

Nomogram for predicting gastric cancer recurrence using biomarker gene expression

BackgroundRecently, researchers have tried to predict patient prognosis using biomarker expression in cancer patients. The aim of this study was to develop a nomogram predicting the 5-year recurrence-free probability (RFP) of gastric cancer patients using prognostic biomarker gene expression.MethodsWe enrolled 360 patients in the training data set to develop the predictive model and nomogram. We analyzed the patients’ general variables and the gene expression levels of 10 prognostic biomarker candidates between the nonrecurrence and recurrence groups. We also performed external validation using 420 patients from the validation data set.ResultsThe final nomogram was composed of age, sex, and the expression levels of CAPZA, PPase, OCT-1, PRDX4, gamma-enolase, and c-Myc. The five-year RFPs were 89%, 75%, 54% and 32% for the patients in the low-risk, intermediate-risk, high-risk and very-high-risk groups in the development cohort, respectively. In the external validation cohort, the 5-year RFPs were 89%, 75%, 63% and 60%, respectively. The areas under the curve were 0.718 (95% CI, 0.65–0.78) and 0.640 (95% CI, 0.57–0.70) for the training and validation data sets, respectively. The RFP Kaplan-Meier curves were significantly different among the 4 groups in the training and validation data sets (p < 0.0001).ConclusionThis newly developed nomogram using gene expression can predict the 5-year RFP for gastric cancer patients after surgical treatment. We hope that this nomogram will help in the therapeutic decision between endoscopic treatment and gastrectomy.