Current role of hepatopancreatoduodenectomy for the management of gallbladder cancer and extrahepatic cholangiocarcinoma:A systematic review

BACKGROUND Hepatopancreatoduodenectomy(HPD)is the simultaneous combination of hepatic resection,pancreaticoduodenectomy,and resection of the entire extrahepatic biliary system.HPD is not a universally accepted due to high mortality and morbidity rates,as well as to controversial survival benefits.AIM To evaluate the current role of HPD for curative treatment of gallbladder cancer(GC)or extrahepatic cholangiocarcinoma(ECC)invading both the hepatic hilum and the intrapancreatic common bile duct.METHODS A systematic literature search using the PubMed,Web of Science,and Scopus databases was performed to identify studies reporting on HPD,using the following keywords:‘Hepatopancreaticoduodenectomy’,‘hepatopancreatoduodenectomy’,‘hepatopancreatectomy’,‘pancreaticoduodenectomy’,‘hepatectomy’,‘hepatic resection’,‘liver resection’,‘Whipple procedure’,‘bile duct cancer’,‘gallbladder cancer’,and‘cholangiocarcinoma’.RESULTS This updated systematic review,focusing on 13 papers published between 2015 and 2020,found that rates of morbidity for HPD have remained high,ranging between 37.0%and 97.4%,while liver failure and pancreatic fistula are the most serious complications.However,perioperative mortality for HPD has decreased compared to initial experiences,and varies between 0%and 26%,although in selected center it is well below 10%.Long term survival outcomes can be achieved in selected patients with R0 resection,although 5–year survival is better for ECC than GC.CONCLUSION The present review supports the role of HPD in patients with GC and ECC with horizontal spread involving the hepatic hilum and the intrapancreatic bile duct,provided that it is performed in centers with high experience in hepatobiliarypancreatic surgery.Extensive use of preoperative portal vein embolization,and preoperative biliary drainage in patients with obstructive jaundice,represent strategies for decreasing the occurrence and severity of postoperative complications.It is advisable to develop internationally-accepted protocols for patient selection,preoperative assessment,operative technique,and perioperative care,in order to better define which patients would benefit from HPD.

Polymorphism AGT2(rs4762)is involved in the development of dermatologic events:Proof-of-concept in hepatocellular carcinoma patients treated with sorafenib

BACKGROUND Dermatologic adverse events(DAEs)are associated with a better outcome in patients with hepatocellular carcinoma(HCC)irrespective of the therapeutic agent received.The exact mechanisms associated with the development of DAEs are unknown although several studies point to direct toxicity of tyrosine kinase inhibitors(TKIs)to the skin or an immune-mediated reaction triggered by the oncologic treatment.As is the case in other conditions,individual genetic variants may partially explain a higher risk of DAEs.AIM To evaluate the contribution of several gene variants to the risk of developing DAEs in HCC patients treated with TKIs.METHODS We first analyzed 27 single-nucleotide polymorphisms(SNPs)from 12 genes selected as potential predictors of adverse event(AE)development in HCC patients treated with sorafenib[Barcelona Clinic Liver Cancer 1(BCLC1)cohort].Three additional cohorts were analyzed for AGT1(rs699)and AGT2(rs4762)polymorphisms-initially identified as predictors of DAEs:BCLC2(n=79),Northern Italy(n=221)and Naples(n=69)cohorts,respectively.The relation between SNPs and DAEs and death were assessed by univariate and multivariate Cox regression models,and presented with hazard ratios and their 95%confidence intervals(95%CI).RESULTS The BCLC1 cohort showed that patients with arterial hypertension(AHT)(HR=1.61;P value=0.007)and/or AGT SNPs had an increased risk of DAEs.Thereafter,AGT2(rs4762)AA genotype was found to be linked to a statistically significant increased probability of DAEs(HR=5.97;P value=0.0201,AA vs GG)in the Northern Italy cohort by multivariate analysis adjusted for BCLC stage,ECOG-PS,diabetes and AHT.The value of this genetic marker was externally validated in the cohort combining the BCLC1,BCLC2 and Naples cohorts[HR=3.12(95%CI:1.2-8.14),P value=0.0199,AGT2(rs4762)AA vs AG genotype and HR=2.73(95%CI:1.18-6.32)P value=0.0188,AGT2(rs4762)AA vs GG genotype].None of the other gene variants tested were found to be associated with the risk of DAE development.CONCLUSION DAE development in HCC patients receiving TKIs could be explained by the AGT2(rs4762)gene variant.If validated in other anti-oncogenic treatments,it might be considered a good prognosis marker.

Colchicine reduces procollagen Ⅲ and increases pseudocholinesterase in chronic liver disease

AIM:To test whether colchicine would be an effective antif ibrotic agent for treatment of chronic liver diseases in patients who could not be treated with α-interferon.METHODS:Seventy-four patients(46 males,28 females) aged 40-66 years(mean 53±13 years) participated in the study.The patients were affected by chronic liver diseases with cirrhosis which was proven histologically(n=58);by chronic active hepatitis C(n=4),chronic active hepatitis B(n=2),and chronic persistent hepatitis C(n=6).In the four patients lacking histology,cirrhosis was diagnosed from anamnesis,serum laboratory tests,esophageal varices and ascites.Patients were assigned to colchicine(1 mg/d) or standard treatment as control in a randomized,double-blind trial,and followed for 4.4 years with clinical and laboratory evaluation.RESULTS:Survival at the end of the study was 94.6% in the colchicine group and 78.4% in the control group(P=0.001).Serum N-terminal peptide of type Ⅲ procollagen levels fell from 34.0 to 18.3 ng/mL(P=0.0001),and pseudocholinesterase levels rose from 4.900 to 5.610 mU/mL(P=0.0001) in the colchicine group,while no signif icant change was seen in controls.Best results were obtained in patients with chronic hepatitis C and in alcoholic cirrhotics.CONCLUSION:Colchicine is an effective and safe antifibrotic drug for long-term treatment of chronic liver disease in which fi brosis progresses towards cirrhosis.

Caspase-cleaved cytokeratin-18 and tumour regression in gastro-oesophageal adenocarcinomas treated with neoadjuvant chemotherapy

AIM:To examine cytokeratin-18(CK-18) and caspasecleaved CK-18 expression in tumours and correlate with clinicopathological outcomes including tumour regression grade(TRG) response.METHODS:Formalin-fixed human gastro-oesophageal cancers were constructed into tissue microarrays.The first set consisted of 122 gastric/gastro-oesophageal cancer cases not exposed to neoadjuvant chemotherapy and the second set consisted of 97 gastric/gastrooesophageal cancer cases exposed to pre-operative platinum-based chemotherapy.Expression of CK-18 and caspase-cleaved CK-18 was investigated using immunohistochemistry.RESULTS:CK18 was commonly expressed in gastrooesophageal tumours(92.6%).Fifty-six point seven percent of tumours previously exposed to neoadjuvant chemotherapy were positive for caspase-cleaved CK-18 expression compared to only 24.6% of tumours not previously exposed to neoadjuvant chemotherapy(P = 0.009).In patients who received neoadjuvant chemotherapy,caspase-cleaved cytokeratin-18 expression correlated with favourable TRG response(TRG 1,2 or 3,P = 0.043).CONCLUSION:This is the largest study to date of CK-18 and caspase-cleaved CK-18 expression in gastrooesophageal tumours.We provide the first evidence that caspase-cleaved CK-18 predicts tumour regression with neoadjuvant chemotherapy.

How the COVID-19 pandemic has affected the colorectal cancer screening in Italy:A minireview

The coronavirus disease 2019(COVID-19)pandemic has caused detrimental effects on many aspects of healthcare practice.Screening programs for the commonest malignancies,namely colorectal cancer(CRC),breast cancer and cervical cancer have been discontinued or interrupted since the beginning of restriction measures aimed to limit transmission of the new coronavirus infection.Robust evidence exists in favour of the role of screening campaigns in reducing mortality from CRC.In fact,the majority of pre-malignant lesions of the colon and rectum can be diagnosed with colonoscopy and treated by endoscopic or surgical resection.Besides,colonoscopy screening allows the diagnosis of CRCs in their pre-clinical stage.Italy was one of the first European countries where a high level of COVID-19 infections and deaths was observed,and one of the first where lockdowns and strict measures were adopted to reduce the risk of COVID-19 diffusion among the population.A systematic review of the literature was performed,including the PubMed,Scopus,Web of Sciences,and Reference Citation Analysis databases,with the aim of critically evaluating the impact of the COVID-19 pandemic on CRC screening in Italy.We found that reduction of CRC screening activity surpassed 50%in most endoscopic units,with almost 600000 fewer CRC screening exams conducted in the first 5 mo of 2020 vs the same period of 2019.While the consequences of the discontinuation of endoscopy screening for the prognosis and mortality of CRC will be evident in the next few years,recent data confirm that CRC is currently treated at a more advanced stage than in the pre-COVID-19 era.Since delays in CRC prevention and early diagnosis may translate to increased CRC-specific mortality,world healthcare systems should adopt strategies to maintain the regularity of CRC screening during subsequent peaks of the COVID-19 pandemic,or future events that might hamper screening programs.