Intraductal papillary neoplasm of the bile duct

Intraductal papillary neoplasm of the bile duct(IPNB)is a variant of bile duct carcinoma that is characterized by intraductal growth and better outcomes compared with common cholangiocarcinoma.IPNBs are mainly found in patients from Far Eastern areas,where hepatolithiasis and clonorchiasis are endemic.According to the immunohistochemical profiles of the mucin core proteins,IPNBs are classified into four types:pancreaticobiliary,intestinal,gastric,and oncocytic.Approximately 40%-80%of IPNBs contain a component of invasive carcinoma or tubular or mucinous adenocarcinoma,suggesting that IPNB is a disease with high potential for malignancy.It is difficult to make an accurate preoperative diagnosis because of IPNB’s low incidence and the lack of specificity in its clinical manifestation.The most common abnormal preoperative imaging findings of IPNB are intraductal masses and the involvement of bile duct dilation.Simultaneous proximal and distal bile duct dilation can be detected in some cases,which has diagnostic significance.Cholangiography and cholangioscopy are needed to confirm the pathology and demonstrate the extent of the lesions.However,pathologic diagnosis by biopsy cannot reflect the actual stage in many cases because different foci may be of different stages and because mixed pathologic findings may exist in the same lesion.Surgical resection is the major treatment.Systematic cholangioscopy with staged biopsies and frozen sections is recommended during resection to ensure that no minor tumors are left and that curative resection is achieved.Staging,histologic subtype,curative resection and lymph node metastasis are factors affecting long-term survival.

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.

γ-glutamyl transferase-to-platelet ratio based nomogram predicting overall survival of gallbladder carcinoma

BACKGROUND Gallbladder carcinoma(GBC)carries a poor prognosis and requires a prediction method.Gamma-glutamyl transferase–to–platelet ratio(GPR)is a recently reported cancer prognostic factor.Although the mechanism for the relationship between GPR and poor cancer prognosis remains unclear,studies have demonstrated the clinical effect of both gamma-glutamyl transferase and platelet count on GBC and related gallbladder diseases.AIM To assess the prognostic value of GPR and to design a prognostic nomogram for GBC.METHODS The analysis involved 130 GBC patients who underwent surgery at Peking Union Medical College Hospital from December 2003 to April 2017.The patients were stratified into a high-or low-GPR group.The predictive ability of GPR was evaluated by Kaplan–Meier analysis and a Cox regression model.We developed a nomogram based on GPR,which we verified using calibration curves.The nomogram and other prognosis prediction models were compared using timedependent receiver operating characteristic curves and the concordance index.RESULTS Patients in the high-GPR group had a higher risk of jaundice,were older,and had higher carbohydrate antigen 19-9 levels and worse postoperative outcomes.Univariate analysis revealed that GPR,age,body mass index,tumor–node–metastasis(TNM)stage,jaundice,cancer cell differentiation degree,and carcinoembryonic antigen and carbohydrate antigen 19-9 levels were related to overall survival(OS).Multivariate analysis confirmed that GPR,body mass index,age,and TNM stage were independent predictors of poor OS.Calibration curves were highly consistent with actual observations.Comparisons of timedependent receiver operating characteristic curves and the concordance index showed advantages for the nomogram over TNM staging.CONCLUSION GPR is an independent predictor of GBC prognosis,and nomogram-integrated GPR is a promising predictive model for OS in GBC.

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.