Hyperamylasemia grade versus drain fluid amylase: which better predicts pancreatectomy outcomes?

BackgroundThe clinical importance of postoperative hyperamylasemia (POHA) grade is unknown. Our objectives were to evaluate the association of POHA grade with clinically relevant postoperative pancreatic fistula (CR-POPF) and compare its prognostic utility against postoperative day 1 drain fluid amylase (DFA-1).MethodsPatients who underwent pancreatectomy from January 2019 through March 2020 were identified in the ACS NSQIP pancreatectomy-targeted dataset. POHA grade was assigned using post-operative serum amylase and clinical sequelae. The primary outcome was CR-POPF within 30 days. The association of POHA grade with CR-POPF was assessed using multivariable logistic regression, and c-statistics were used to compare POHA grade versus DFA-1.ResultsPOHA occurred in 520 patients at 98 hospitals, including 261 (50.2%) with grade A, 234 (45.0%) with grade B, and 25 (4.8%) with grade C POHA. CR-POPFs were increased among patients with grade B (66.2%, OR 9.28 [5.84–14.73]) and C (68.0%, OR 10.50 [3.77–29.26]) versus grade A POHA (19.2%). POHA-inclusive models better predicted CR-POPF than those with DFA-1 alone (p < 0.002) and models with both predictors outperformed POHA alone (p = 0.039).ConclusionPOHA grade represents a measure of post-pancreatectomy outcomes that predicts CR-POPF and outperforms DFA-1 but must be aligned with new international definitions.     

The reality of cholangiocarcinoma in India– real world data from a tertiary referral centre

BackgroundCholangiocarcinomas (CCA) are rare tumours originating from bile duct. Due to their asymptomatic nature they are usually diagnosed when the disease is advanced. Little data exists with respect to their incidence and treatment outcomes in low and middle income countries.MethodA retrospective analysis of a prospectively maintained database of all patients with perihilar (pCCA) and intrahepatic (iCCA) CCA registered between January 2012 and December 2018 was performed.ResultsA total of 760 patients, 427 (56.2%) diagnosed with pCCA and 333 (43.8%) of iCCA were included. Patients with localised, locally advanced and metastatic disease in pCCA were 45.5%, 25.9%, 8.5% and that in iCCA were 22.1%, 10.1% and 67.7% respectively. Only 141 (43.9%, 57 - iCCA, 84 -pCCA) of the total 321 patients started on some definitive cancer directed therapy could complete the intended treatment. The overall curative resection rate for all patients of iCCA was 14.5% whereas for patients of pCCA it was only 10.5%.ConclusionMore than half of CCA patients are not able to complete their intended treatment, being worse for pCCA as compared to iCCA. Early referral and centralisation of treatment for this complex disease might be the way forward to achieve optimal outcomes.     

Prognostic models to predict survival in patients with pancreatic cancer: a systematic review

BackgroundPancreatic ductal adenocarcinoma (PDAC) has poor survival. Current treatments offer little likelihood of cure or long-term survival. This systematic review evaluates prognostic models predicting overall survival in patients diagnosed with PDAC.MethodsWe conducted a comprehensive search of eight electronic databases from their date of inception through to December 2019. Studies that published models predicting survival in patients with PDAC were identified.Results3297 studies were identified; 187 full-text articles were retrieved and 54 studies of 49 unique prognostic models were included. Of these, 28 (57.1%) were conducted in patients with advanced disease, 17 (34.7%) with resectable disease, and four (8.2%) in all patients. 34 (69.4%) models were validated, and 35 (71.4%) reported model discrimination, with only five models reporting values >0.70 in both derivation and validation cohorts. Many (n = 27) had a moderate to high risk of bias and most (n = 33) were developed using retrospective data. No variables were unanimously found to be predictive of survival when included in more than one study.ConclusionMost prognostic models were developed using retrospective data and performed poorly. Future research should validate instruments performing well locally in international cohorts and investigate other potential predictors of survival.     

Prognostic validity of the American joint committee on cancer eighth edition staging system for well-differentiated pancreatic neuroendocrine tumors

BackgroundThe American Joint Committee on Cancer (AJCC) made improvements for staging pancreatic neuroendocrine tumors (pNETs) in its 8th Edition; however, multicenter studies were not included.MethodsWe collected multicenter datasets (n = 1,086, between 2004 and 2018) to validate the value of AJCC 8 and other coexisting staging systems through univariate and multivariate analysis for well-differentiated (G1/G2) pNETs.ResultsCompared to other coexisting staging systems, AJCC 7 only included 12 (1.1%) patients with stage III tumors. Patients with European Neuroendocrine Tumor Society (ENETS) stage IIB disease had a higher risk of death than patients with stage IIIA (hazard ratio [HR]: 4.376 vs. 4.322). For the modified ENETS staging system, patients with stage IIB disease had a higher risk of death than patients with stage III (HR: 6.078 vs. 5.341). According to AJCC 8, the proportions of patients with stage I, II, III, and IV were 25.7%, 40.3%, 23.6%, and 10.4%, respectively. As the stage advanced, the median survival time decreased (NA, 144.7, 100.8, 72.0 months, respectively), and the risk of death increased (HR: II = 3.145, III = 5.925, and IV = 8.762).ConclusionThese findings suggest that AJCC 8 had a more reasonable proportional distribution and the risk of death was better correlated with disease stage.     

A meta-analysis on salvage surgery as a potentially curative procedure in patients with isolated local recurrent or persistent esophageal cancer after chemoradiotherapy

BackgroundIsolated local recurrent or persistent esophageal cancer (EC) after curative intended definitive (dCRT) or neoadjuvant chemoradiotherapy (nCRT) with initially omitted surgery, is a potential indication for salvage surgery. We aimed to evaluate safety and efficacy of salvage surgery in these patients.Material and methodsA systematic literature search following PRISMA guidelines was performed using databases of PubMed/Medline. All included studies were performed in patients with persistent or recurrent EC after initial treatment with dCRT or nCRT, between 2007 and 2017. Survival analysis was performed with an inverse-variance weighting method.ResultsOf the 278 identified studies, 28 were eligible, including a total of 1076 patients. Postoperative complications after salvage esophagectomy were significantly more common among patients with isolated persistent than in those with locoregional recurrent EC, including respiratory (36.6% versus 22.7%; difference in proportion 10.9 with 95% confidence interval (CI) [3.1; 18.7]) and cardiovascular complications (10.4% versus 4.5%; difference in proportion 5.9 with 95% CI [1.5; 10.2]). The pooled estimated 30- and 90-day mortality was 2.6% [1.6; 3.6] and 8.0% [6.3; 9.8], respectively. The pooled estimated 3-year and 5-year overall survival (OS) were 39.0% (95% CI: [35.8; 42.2]) and 19.4% [95% CI:16.5; 22.4], respectively. Patients with isolated persistent or recurrent EC after initial CRT had similar 5-year OS (14.0% versus 19.7%, difference in proportion −5.7, 95% CI [-13.7; 2.3]).ConclusionsSalvage surgery is a potentially curative procedure in patients with locally recurrent or persistent esophageal cancer and can be performed safely after definitive or neoadjuvant chemoradiotherapy when surgery was initially omitted.     

Major hepatectomy for intrahepatic cholangiocarcinoma or colorectal liver metastases. Are we talking about the same story?

IntroductionMajor hepatectomy (MH) is often needed in the curative management of intrahepatic cholangiocarcinoma (IHCC) and colorectal liver metastases (CRLM). While similar outcomes could be expected after MH for IHCC and CRLM, outcomes seem worse after MH for IHCC. A better understanding of such differences might help improving perioperative outcomes but comprehensive analysis are lacking.MethodsAll patients undergoing curative intent MH for IHCC or CRLM from 2003 to 2009 were included from two dedicated multi-institutional datasets. Preoperative management and short-term outcomes after MH were first compared. Independent predictors of postoperative mortality and morbidity were identified.ResultsAmong 827 patients, 333 and 494 patients underwent MH for IHCC and CRLM, respectively. Preoperative portal vein embolization was more frequently performed in the CRLM group (p < 0.001). MH in the IHCC group required more extended resection (p < 0.001). Postoperative mortality and severe morbidity rates were significantly higher in the IHCC group (7.2% vs. 1.2% and 29.7% vs. 11.1%, p < 0.001, respectively). Main causes for mortality were postoperative liver failure and deep surgical site infection. MH for IHCC was an independent risk factor for mortality (p < 0.001) and severe morbidity (p < 0.001). After propensity score matching (212 patients in each group), the aforementioned differences regarding outcomes remained statistically significant.ConclusionThis study suggests that IHCC patients are inherently more at risk after MH as compared to CRLM patients. Considering that postoperative liver failure was the most frequent cause of death, preoperative planning might have been inadequate in the setting of IHCC while more complex/extended resections should be expected.     

The largest western experience on salvage hepatectomy for recurrent hepatocellular carcinoma: propensity score-matched analysis on behalf of He.RC.O.Le.Study Group

BackgroundWe aimed to evaluate, in a large Western cohort, perioperative and long-term oncological outcomes of salvage hepatectomy (SH) for recurrent hepatocellular carcinoma (rHCC) after primary hepatectomy (PH) or locoregional treatments.MethodsData were collected from the Hepatocarcinoma Recurrence on the Liver Study Group (He.RC.O.Le.S.) Italian Registry. After 1:1 propensity score-matched analysis (PSM), two groups were compared: the PH group (patients submitted to resection for a first HCC) and the SH group (patients resected for intrahepatic rHCC after previous HCC-related treatments).Results2689 patients were enrolled. PH included 2339 patients, SH 350. After PSM, 263 patients were selected in each group with major resected nodule median size, intraoperative blood loss and minimally invasive approach significantly lower in the SH group. Long-term outcomes were compared, with no difference in OS and DFS. Univariate and multivariate analyses revealed only microvascular invasion as an independent prognostic factor for OS.ConclusionSH proved to be equivalent to PH in terms of safety, feasibility and long-term outcomes, consistent with data gathered from East Asia. In the awaiting of reliable treatment-allocating algorithms for rHCC, SH appears to be a suitable alternative in patients fit for surgery, regardless of the previous therapeutic modality implemented.     

维纳托克在肝癌细胞中的抗肿瘤活性及其机制

目的探讨维纳托克(Venetoclax)在HepG2、Hep3B 2个肝癌细胞株的抗癌活性。方法对人肝癌细胞株HepG2、Hep3B细胞株进行体外培养,采用不同浓度的Venetoclax(0、3、10、30μmol/L)处理肝癌细胞,以细胞计数试剂盒(CCK-8)检测细胞活性,0,3,10和30μmol/L Venetoclax作用细胞48 h,锥虫蓝拒染法检测细胞的死亡,0,5μmol/L Venetoclax,作用24 h,流式细胞学检测细胞凋亡率,蛋白质印迹法(Western blot)检测Venetoclax诱导半胱氨酰天冬氨酸特异性蛋白酶(Caspase)-3活化,聚腺苷二磷酸核糖聚合酶(PARP)裂解。组间比较采用t检验。结果Venetoclax对HepG2、Hep3B细胞株均有较强活性抑制作用。不同浓度的Venetoclax处理肝癌细胞48、72 h,Venetoclax在HepG2细胞株中取得的半数细胞活性抑制率(IC50)值分别为46.5μmol/L和14.2μmol/L;在Hep3B细胞的IC50值分别为24.6μmol/L和11.2μmol/L。处理24 h,30.0μmol/L的Venetoclax在HepG2和Hep3B细胞株中诱导57%[对照组、实验组凋亡率分别为(4.00±1.00)%、(56.67±8.51)%,t=-10.650,P<0.01]和54%[对照组、实验组凋亡率分别为(5.67±1.53)%、(54.33±9.87)%,t=-8.440,P<0.01]的肝癌细胞发生凋亡,并能诱导肝癌细胞的Caspase-3活化,PARP裂解,差异均有统计学意义。用0、3、10和30μmol/L的Venetoclax处理48 h,在HepG2细胞株中可诱导3%(3.26±1.71)%,12%[(12.36±1.99)%,(t=-12.36,P<0.05)],32%[(32.38±4.57)%,(t=-10.350,P<0.01)]和67%[(66.71±6.29)%,(t=-16.86,P<0.01)]的细胞死亡,差异均有统计学意义;在Hep3B细胞株诱导2%(1.91±0.68)%,16%[(15.72±3.40)%,(t=-6.890,P<0.05)],42%[(42.39±6.86)%,(t=-10.180,P<0.01)]和73%[(73.32±2.69)%,t=-44.490,P<0.01]的细胞死亡,差异均有统计学意义。应用半胱氨酸蛋白酶(Caspase)抑制剂预处理,Venetoclax对HepG2和Hep3B细胞的死亡率分别从56%(56.71±6.29)%降低至11%(10.70±1.43)%,(t=12.350,P<0.01)和68%(68.05±10.16)%至12%(12.7±6.12)%,(t=8.080,P<0.01),差异有统计学意义。结论Venetoclax能够通过诱导Caspase的活化,诱导肝癌细胞发生凋亡,并对肝癌细胞进行杀伤。