Neoadjuvant chemoradiotherapy before resection of perihilar cholangiocarcinoma: A systematic review

Background: Treatment with neoadjuvant chemoradiotherapy followed by liver transplantation yields promising results in perihilar cholangiocarcinoma (PH-CCA). This study reviews the literature to assess whether there is evidence to justify modern phase Ⅱ studies of neoadjuvant chemoradiotherapy prior to resection of PH-CCA.Data sources: A systematic review of the literature for reports of patients undergoing resection of PH- CCA after neoadjuvant chemoradiotherapy was performed using MEDLINE and EMBASE databases for the period between 1990 and 2019. The keywords and MeSH headings "hilar cholangiocarcinoma", "Klatskin", "chemoradiotherapy" and "chemotherapy" were used. Data were extracted on demographic profile, dis- ease staging, chemoradiotherapy protocols, complications and outcome. Risks of bias were assessed using Cochrane methodology. Results: There were seven reports on this topic, with median recruitment period of 14 (range 4–31) years. The total number of patients in these studies was 87. Interval from completion of neoadjuvant treatment to surgery varied from 3 days to 6 months. Resection was by hepatectomy with three studies reporting an R0 rate of 100%, 24% and 63%, respectively. Three studies reported histopathological evidence of prior treatment response. There were two treatment related deaths at 90 days. Median survival was 19 (95% CI: 9.9–28) months and 5-year survival 20%. Conclusions: There are potential benefits of treatment on both R0 rate and complete response in resected specimens. Scientific equipoise exists in relation to neoadjuvant chemoradiotherapy for PH-CCA.

Glucose metabolic phenotype of pancreatic cancer

AIM: To construct a global "metabolic phenotype" of pancreatic ductal adenocarcinoma(PDAC) reflecting tumour-related metabolic enzyme expression.METHODS: A systematic review of the literature was performed using Ovid SP and Pub Med databases using keywords "pancreatic cancer" and individual glycolytic and mitochondrial oxidative phosphorylation(MOP) enzymes. Both human and animal studies investigating the oncological effect of enzyme expression changes and inhibitors in both an in vitro and in vivo setting were included in the review. Data reporting changes in enzyme expression and the effects on PDAC cells, such as survival and metastatic potential, were extracted to construct a metabolic phenotype. RESULTS: Seven hundred and ten papers were initially retrieved, and were screened to meet the review inclusion criteria. 107 unique articles were identified as reporting data involving glycolytic enzymes, and 28 articles involving MOP enzymes in PDAC. Data extraction followed a pre-defined protocol. There is consistent over-expression of glycolytic enzymes and lactate dehydrogenase in keeping with the Warburg effect to facilitate rapid adenosine-triphosphate production from glycolysis. Certain isoforms of these enzymes were over-expressed specifically in PDAC. Altering expression levels of HK, PGI, FBA, enolase, PK-M2 and LDA-A with metabolic inhibitors have shown a favourable effect on PDAC, thus identifying these as potential therapeutic targets. However, the Warburg effect on MOP enzymes is less clear, with different expression levels at different points in the Krebs cycle resulting in a fundamental change of metabolite levels, suggesting that other essential anabolic pathways are being stimulated. CONCLUSION: Further characterisation of the PDAC metabolic phenotype is necessary as currently there are few clinical studies and no successful clinical trials targeting metabolic enzymes.

Non-operative management of pancreatic trauma in adults

To the Editor:Pancreatic trauma accounts for 0.4%-2.0%of all trauma-related injuries worldwide[1-3].The American Association for the Surgery of Trauma(AAST)categorizes pancreatic injury according to the severity[4].Pancreatic injury involving transection of the gland(grades III to V)typically requires surgical management[4].However,pancreatic trauma,especially in children and young adults,can be managed without surgery[5].This study reports the outcome of a policy of preferential non-operative management of pancreatic trauma in adults.

Computed tomographic angiography for diagnosis of post-pancreatoduodenectomy hemorrhage

To the Editor:Even in high volume specialist hepato-pancreato-biliary surgery centres,hemorrhage after pancreatoduodenectomy remains a feared and potentially lethal complication[1]and an important cause of postoperative morbidity and mortality[2].Whilst early hemorrhage after pancreatoduodenectomy is typically managed by re-operation,detection and treatment of bleeding later in the postoperative course can be problematic.Patients who are hemodynamically unstable with evidence of brisk bleeding are usually treated by urgent re-operation.However,not all bleeding episodes present in such a dramatic fashion.The“sentinel bleed”–a harbinger of major hemorrhage–represents a clinical opportunity for detection and treatment[3].Traditionally,patients who presented with luminal bleeding episodes with hematemesis or melena underwent fibre optic endoscopy as first-line investigation whereas patients presenting with a bleed into surgical drains would have undergone selective mesenteric angiography[4].

The terminology of the 2012 Atlanta consensus conference on post-inflammatory collections after acute pancreatitis:An assessment of utilization in practice

To the Editor The report of the 1992 Atlanta consensus conference provided a framework for standardization of the terminology for description of acute pancreatitis and its complications[1].Terms such as“pancreatic phlegmon”which had historically been subjected to differential interpretation were discontinued and modern terminology was introduced[1].With subsequent clinical usage and with the accrual of new knowledge it became clear that further changes were necessary.

Multidisciplinary management of patients with post-inflammatory pancreatic necro

Current knowledge of the pathophysiology of acute pancreatitis indicates that pancreatic injury originates at the acinar cell level and then extends through a spectrum of damage ranging from mild peri-acinar inflammatory infiltration and edema to extensive pancreatic parenchymal and peri-pancreatic necrosis[1,2].Clinical acute pancreatitis correlates closely with this range of injury with the majority of patients experiencing mild disease,some having transient organ dysfunction which typically recovers after adequate resuscitation(moderate acute pancreatitis)and a variable minority exhibiting sustained organ failure together with radiological evidence of pancreatic necrosis(severe acute pancreatitis)[2,3].Worldwide,the management of this latter category of patients with severe acute pancreatitis remains a challenge.There is no effective direct medical treatment and there is no role for early pancreatic debridement[3,4].This article provides a concise summary of current multidisciplinary management of patients with post-inflammatory pancreatic necrosis.

Reporting of longitudinal pancreatojejunostomy with partial pancreatic head resection(the Frey procedure) for chronic pancreatitis: A systematic review

Background:Longitudinal pancreatojejunostomy with partial pancreatic head resection(the Frey procedure)is accepted for surgical treatment of painful chronic pancreatitis.However,conduct and reporting are not standardized and thus,making comparisons difficult.This study assesses the reporting standards of this procedure.Data sources:A systematic literature review was performed between January 1987 and January 2020.The keyword and Medical Subject Heading"chronic pancreatitis"was used together with the individual operation term"Frey pancreatojejunostomy".Reports were included if they provided original information on conduct and outcome.Thirty-three papers providing information on 1205 patients constituted the study population.Risk of bias in included reports was assessed.Results:Etiology of chronic pancreatitis(alcohol)was reported in 26 of 28(93%)studies,duration of symptoms prior to surgery in 19(58%)studies and pre-operative opiate use in 12(36%)studies.In terms of morphology,pancreatic duct diameter was reported in 17(52%)studies and diameter of the pancreatic head in 13(39%)studies.In terms of technique,three(9%)studies reported weight of excised parenchyma.There were 9(0.7%)procedure-related deaths.Post-operative follow-up ranged from 6 to 82.5 months.No studies reported post-operative portal hypertension.Conclusions:There is substantial heterogeneity between studies in reporting of clinical baseline,morphology of the diseased pancreas,operative detail and outcome after longitudinal pancreatojejunostomy with partial pancreatic head resection.This critically compromises the comparison between centers and between surgeons.Structured reporting is necessary for clinicians to assess choice of procedure and for patients to make informed choices when seeking treatment for painful chronic pancreatitis.