Albumin-to-alkaline phosphatase ratio: A novel prognostic index of overall survival in cholangiocarcinoma patients after surgery

AIM To clarify the prognostic significance of preoperative albumin-to-alkaline phosphatase ratio(AAPR) in cholangiocarcinoma(CCA) subjects receiving surgery.METHODS In this retrospective study, we included 303 CCA patients receiving surgery without preoperative therapy between 2002 and 2014. Clinicopathological characteristics(including AAPR) were analyzed to determine predictors of postoperative overall survival and recurrence-free survival(RFS). In addition,univariate and multivariate Cox proportional hazards models were conducted,followed by application of time-dependent receiver operating curves to identify the optimal cut-off.RESULTS Univariate and multivariate analyses revealed both decreased overall survival[hazard ratio(HR): 2.88, 95%CI: 1.19-5.78] and recurrence-free survival(HR: 2.31,95%CI: 1.40–3.29) in patients with AAPR < 0.41 compared to those with AAPR ≥0.41. The optimal cut-off of AAPR was 0.41. Of the 303 subjects, 253(83.5%) had an AAPR over 0.41. The overall 1-, 3- and 5-year survival rates were 70.2%, 38.0% and 16.5%, respectively in the low(< 0.41) AAPR group, which were significantly lower than those in the high(≥ 0.41) AAPR group(81.7%, 53.9%, and 33.4%,respectively)(P < 0.0001). Large tumor size, multiple tumors, and advanced clinical stage were also identified as significant predictors of poor prognosis.CONCLUSION Our outcomes showed that AAPR was a potential valuable prognostic indicator in CCA patients undergoing surgery, which should be further confirmed by prospective studies. Moreover, it is necessary to investigate the mechanisms concerning the correlation of low AAPR with poor post-operative survival in CCA patients.

Complete or partial split in associating liver partition and portal vein ligation for staged hepatectomy: A systematic review and meta-analysis

BACKGROUND Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)has been adopted by liver surgeons in recent years.However,high morbidity and mortality rates have limited the promotion of this technique.Some recent studies have suggested that ALPPS with a partial split can effectively induce the growth of future liver remnant(FLR)similar to a complete split with better postoperative safety profiles.However,some others have suggested that ALPPS can induce more rapid and adequate FLR growth,but with the same postoperative morbidity and mortality rates as in partial split of the liver parenchyma in ALPPS(p-ALPPS).AIM To perform a systematic review and meta-analysis on ALPPS and p-ALPPS.METHODS A systematic literature search of PubMed,Embase,the Cochrane Library,and ClinicalTrials.gov was performed for articles published until June 2019.Studies comparing the outcomes of p-ALPPS and ALPPS for a small FLR in consecutive patients were included.Our main endpoints were the morbidity,mortality,and FLR hypertrophy rates.We performed a subgroup analysis to evaluate patients with and without liver cirrhosis.We assessed pooled data using a random-effects model.RESULTS Four studies met the inclusion criteria.Four studies reported data on morbidity and mortality,and two studies reported the FLR hypertrophy rate and one study involved patients with cirrhosis.In the non-cirrhotic group,p-ALPPS-treated patients had significantly lower morbidity and mortality rates than ALPPStreated patients[odds ratio(OR)=0.2;95%confidence interval(CI):0.07–0.57;P=0.003 and OR=0.16;95%CI:0.03-0.9;P=0.04].No significant difference in the FLR hypertrophy rate was observed between the two groups(P>0.05).The total effects indicated no difference in the FLR hypertrophy rate or perioperative morbidity and mortality rates between the ALPPS and p-ALPPS groups.In contrast,ALPPS seemed to have a better outcome in the cirrhotic group.CONCLUSION The findings of our study suggest that p-ALPPS is safer than ALPPS in patients without cirrhosis and exhibits the same rate of FLR hypertrophy.

Signature based on molecular subtypes of deoxyribonucleic acid methylation predicts overall survival in gastric cancer

BACKGROUND Gastric cancer(GC) ranks as the third leading cause of cancer-related death worldwide. Epigenetic alterations contribute to tumor heterogeneity in early stages.AIM To identify the specific deoxyribonucleic acid(DNA) methylation sites that influence the prognosis of GC patients and explore the prognostic value of a model based on subtypes of DNA methylation.METHODS Patients were randomly classified into training and test sets. Prognostic DNA methylation sites were identified by integrating DNA methylation profiles and clinical data from The Cancer Genome Atlas GC cohort. In the training set, unsupervised consensus clustering was performed to identify distinct subgroups based on methylation status. A risk score model was built based on Kaplan-Meier, least absolute shrinkage and selector operation, and multivariate Cox regression analyses. A test set was used to validate this model.RESULTS Three subgroups based on DNA methylation profiles in the training set were identified using 1061 methylation sites that were significantly associated with survival. These methylation subtypes reflected differences in T, N, and M category, age, stage, and prognosis. Forty-one methylation sites were screened as specific hyper-or hypomethylation sites for each specific subgroup. Enrichment analysis revealed that they were mainly involved in pathways related to carcinogenesis, tumor growth, and progression. Finally, two methylation sites were chosen to generate a prognostic model. The high-risk group showed a markedly poor prognosis compared to the low-risk group in both the training [hazard ratio(HR) = 2.24, 95% confidence interval(CI): 1.28-3.92, P < 0.001] and test(HR = 2.12, 95%CI: 1.19-3.78, P = 0.002) datasets.CONCLUSION DNA methylation-based classification reflects the epigenetic heterogeneity of GC and may contribute to predicting prognosis and offer novel insights for individualized treatment of patients with GC.

Pembrolizumab combined with lenvatinib as non-first-line therapy in patients with refractory biliary tract carcinoma

Background:A therapeutic strategy involving combined treatment with lenvatinib plus pembrolizumab(LEP)has demonstrated a relatively high antitumor response in several solid tumors;however,the efficacy and safety of LEP in patients with refractory bile tract carcinoma(BTC)remains unknown.Methods:This is a single-arm study for a preliminary assessment of the efficacy and tolerability of LEP in patients who experienced progression from prior systemic treatments.Pre-treatment tumor tissues were collected to retrospectively evaluate the expression status of PDL1.Results:Thirty-two patients received second-line and above treatment with LEP.Overall,the objective response rate(ORR)was 25%,the disease control rate(DCR)was 78.1%,and the clinical benefit rate(CBR)was 40.5%.The median progression-free survival(PFS)was 4.9 months(95%CI:4.7–5.2 months),and the median overall survival(OS)was 11.0 months(95%CI:9.6–12.3 months).For tolerability,no grade 5 serious adverse events(AEs)were reported.All patients had any-grade AEs,and 59.3%of the patients experienced grade 3 AEs,while only 1 patient experienced a grade 4 AE of stomach bleeding.Fatigue was the most common AE,followed by hypertension and elevated aminotransferase levels.Retrospective analysis for PDL1 expression revealed that PDL1 positive tumor cells were associated with improved clinical benefits and survival outcomes.Conclusions:LEP is a promising alternative as a non-first-line therapeutic regimen for patients with refractory BTC.Furthermore,well-designed prospective clinical trials with a control arm are still needed to obtain more evidences to confirm the efficacy and safety of this particular regimen as well as the role of PDL1 expression.

Downstaging and resection of hepatocellular carcinoma in patients with extrahepatic metastases after stereotactic therapy

Background:A combination of tyrosine kinase inhibitors(TKIs)and anti-PD-1 antibodies with local regional therapy has elicited yield substantial clinical benefits in patients who have hepatocellular carcinoma(HCC)with extrahepatic metastases.Using this treatment strategy to convert HCC patients with extrahepatic metastases from unresectable to resectable has not yet been reported.Methods:Consecutive hepatocellular carcinoma patients with extrahepatic metastases who received first-line therapy with a combination of TKIs and anti-PD-1 antibodies and at least one local regional therapy were analysed.Results:Nine patients with localized disease who received first-line systemic therapy were enrolled.At baseline,all of them had oligometastatic disease,namely,Barcelona Clinic Liver Cancer stage C(or Chinese Liver Cancer stage IIIB).The most common treatment administered was lenvatinib plus anti-PD-1 antibody and transarterial chemoembolization,and the median time span from systemic therapy to surgery was 3.2(IQR,2.8-6.2)months.Three patients achieved a pathological complete response.Six patients underwent laparoscopic surgery,and the other 3 patients underwent open surgery.After a median follow-up of 10.2(IQR,8.6-20.0)months,7 patients survived without disease recurrence,and 2 experienced tumour recurrence.All patients had any-grade AEs,and 55.6%of the patients experienced grade 3 AEs.Fatigue was the most common AE,followed by elevated aminotransferase levels and hypertension.Conclusions:Stereotactic therapy is a feasible conversion therapy for HCC patients with extrahepatic metastases to become resectable.This is the first study to analyse therapeutic outcomes of patients receiving these therapies for HCC with extrahepatic metastases.

Single Nucleotide Polymorphism rs10919543 in FCGR2A/ FCGR3A Region Confers Susceptibility to Takayasu Arteritis in Chinese Population

Background： Takayasu arteritis （TA） is a rare inflammatory arteriopathy of unknown etiology. The aim of this study was to investigate the genetic susceptibility to TA in a Chinese population. Methods： Four single nucleotide polymorphisms （SNPs） those locate in the IL12B region （rs56167332）, the MLX region （rs665268）, the FCGR2A/FCGR3A locus （rsi0919543）, and the HLA-B/M1CA locus （rs12524487）, associated with TA in different population, were genotyped in 123 Chinese TA patients and 147 healthy controls from January 2013 to August 2014. A Chi-square test was used to test for genotype/allele frequencies variants. Results： Among the four SNPs, rs 10919543 was found to be significantly associated with TA in the studied population. The GG genotype of rs 10919543 at the FCGR2A/FCGR3A locus is a high risk factor （odds ratio [OR] = 6.532, 95% confidence interval [C1] = 2.402 - 17.763, P 〈 0.001 ） for TA. Among TA patients, the level of eosinophil granulocytes （Eos） in the peripheral blood was observed to be higher in the GG group of rs 10919543 （n = 23, Eos = 0. I 1 [0.08, 0.17] x 109/L） than the GA ＋ AA group （n = 100, Eos = 0.08 [0.05, 0.13] 10/L, P = 0.028）. No correlation between the genotypes of the other three SNPs and TA patients was observed. Conclusions： Our findings revealed unique genetic pattern in Chinese TA patients that may be partly responsible for the higher risk of TA in this population. FCGR2A/FCGR3A-related immune disorder might contribute to the etiology of TA.