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World Journal of Gastroenterology 2014年第11期20卷 3033-3043页

作者： ajith k siriwardena Hepatobiliary Surgery Unit Manchester Royal InfirmaryManchester M13 9WLUnited Kingdom

AIM: To reappraise the hypothesis of xenobiotic induced, cytochrome P450-mediated, micronutrient-deficient oxidative injury in chronic pancreatitis.

关键词： Chronic pancreatitis Cellular injury Oxidative stress Xenobiotics Cytochrome P450

Long-term outcome of patients with chronic pancreatitis treated with micronutrient antioxidant therapy

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Hepatobiliary & Pancreatic Diseases International 2017年第2期16卷 209-214页

作者： Sukitha Namal Rupasinghe ajith k siriwardena Hepatobiliary Surgery Unit Manchester Royal Infirmary Oxford Road Manchester M13 9WL UK

BACkGROUND： Micronutrient antioxidant therapy did not relieve pain in a European randomized trial of patients with chronic pancreatitis without malnutrition. However, intervention was undertaken only for 6 months leaving unanswered the question of whether long-term antioxidant therapy may modulate chronic pancreatitis. The aim of this study is to assess the outcome of long-term use of micronutrient antioxidant therapy in patients with chronic ***： This is a single center clinical cohort report of patients with chronic pancreatitis prescribed micronutrient antioxidant therapy and followed for up to 10 years. Data were collected on demographic detail, clinic pain assessment, insulin requirements, interventions and ***： A group of 30 patients with a diagnosis of chronic pancreatitis constitute the study population. Median age at time of diagnosis was 40 years（range 14-66）; 19（63%） were male and the median duration of symptoms was 2 years（range 0-18）. Alcohol was the dominant cause in 22（73%） patients and 16（53%） patients were Cambridge stage 1. Twenty-four（80%） patients had pain at presentation. During antioxidant treatment of 4 years（range 1-10）, pain decreased but the proportion with abdominal pain compared to those who were pain-free remained constant（P=0.16; two-way ANOVA with Bonferroni correction）. There was a significant increase in requirement for insulin（P=0.028） with time together with use of both endoscopic and surgical ***： This is the first study to report long-term disease-specific outcome in patients with chronic pancreatitis prescribed micronutrient antioxidant therapy. There appears to be no effect of intervention on outcome.

关键词： chronic pancreatitis antioxidant therapy micronutrient Antox outcomes

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

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Hepatobiliary & Pancreatic Diseases International 2021年第2期20卷 110-116页

作者： Minas Baltatzis Santhalingam Jegatheeswaran ajith k siriwardena Regional Hepato-Pancreato-Biliary Surgery Unit Manchester Royal InfirmaryOxford RoadManchester M139WLUK Faculty of Biology Medicine and HealthUniversity of ManchesterManchesterUK

Background:Longitudinal pancreatojejunostomy with partial pancreatic head resection(the Frey procedure)is accepted for surgical treatment of painful chronic ***,conduct and reporting are not standardized and thus,making comparisons *** study assesses the reporting standards of this *** sources:A systematic literature review was performed between January 1987 and January *** 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 ***-three papers providing information on 1205 patients constituted the study *** of bias in included reports was ***: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%)*** terms of morphology,pancreatic duct diameter was reported in 17(52%)studies and diameter of the pancreatic head in 13(39%)*** terms of technique,three(9%)studies reported weight of excised *** were 9(0.7%)procedure-related ***-operative follow-up ranged from 6 to 82.5 *** studies reported post-operative portal ***: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 *** critically compromises the comparison between centers and between *** reporting is necessary for clinicians to assess choice of procedure and for patients to make informed choices when seeking treatment for painful chronic pancreatitis.

关键词： Chronic pancreatitis Frey procedure Reporting Longitudinal pancreatojejunostomy

Cytokine profiles in patients receiving antioxidant therapy within the ANTICIPATE trial

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World Journal of Gastroenterology 2013年第25期19卷 4001-4006页

作者： Nehal Shah ajith k siriwardena Hepato-Pancreato-Biliary Surgery Unit Manchester Royal Infirmary

AIM: To measure a broad profile of pro-and anti-inflammatory cytokines in patients with clinically proven chronic pancreatitis (CP) taking either antioxidant therapy or placebo as part of the larger ANTICIPATE study. METHODS: Patients with chronic pancreatitis were recruited to the ANTICIPATE study following informed consent and were randomised to intervention with either antox version 1.2-based antioxidant therapy or placebo. After a separate ethics committee amendment a subgroup of 7 patients from either arm of the study were selected for additional analysis of cytokines. Cytokines were measured at baseline and after 6 mo of either antox therapy or placebo by biochip array and enzyme-linked immunosorbent assay. RESULTS: Antioxidant therapy and placebo groups were well-matched in terms of age, gender, aetiology of CP, opiate use and disease duration. Baseline antioxidant levels were similar in patients allocated to the antioxidant group as compared to the group al- located to placebo. After 6 mo of antioxidant therapythere was significant elevation in vitamin C levels in the intervention group: 17.6 μg/mL (12.8-29.3 μg/mL) compared to 4.8 μg/mL (1.6-9.1 μg/mL) in placebo (P kines in the antioxidant group compared to placebo [interleukin (IL)-1B, IL-4, IL-6, IL-10, tumor necrosis factor-α] either at baseline or after 6 mo of antioxidant therapy. CONCLUSION: Cytokine levels were low at baseline and at 6 mo despite a significant elevation in plasma antioxidants. In patients with CP, with opiate-dependent abdominal pain, circulating cytokine levels are low suggesting that pain in this disease is not simply a manifestation of inflammation.

关键词： Chronic pancreatitis Antioxidant therapy Cytokine

Neoadjuvant chemoradiotherapy before resection of perihilar cholangiocarcinoma: A systematic review

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Hepatobiliary & Pancreatic Diseases International 2020年第2期19卷 103-108页

作者： Minas Baltatzis Santhalingam Jegatheeswaran ajith k.siriwardena Regional Hepato-Pancreato-Biliary Surgery Unit Manchester Royal InfirmaryOxford RoadManchester M139WLUK Faculty of Biology Medicine and HealthUniversity of ManchesterManchester M139WLUK

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 *** 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.

关键词： Perihilar cholangiocarcinoma Neoadjuvant Chemotherapy Radiotherapy Surgery

Improving definition of the term “synchronous liver metastases” from colorectal cancer

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Hepatobiliary & Pancreatic Diseases International 2016年第5期15卷 458-460页

作者： Anthony kC Chan ajith k siriwardena Hepatobiliary Surgery Unit Manchester Royal Infirmary 0xford Road Manchester M13 9WL UK

The liver is the most frequent site of metastasis in colorectal cancer with up to a quarter of patients having liver metastases at the time of initial diagnosis and a further third subsequently developing liver *** who present with metastatic liver disease after treatment of the primary(termed metachronous disease)receive care focused on this new metastatic *** contrast,the management of patients who present with colorectal cancer and concurrent liver

关键词： Improving definition of the term synchronous liver metastases from colorectal cancer

Multidisciplinary management of patients with post-inflammatory pancreatic necro

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Hepatobiliary & Pancreatic Diseases International 2021年第1期20卷 1-3页

作者： Santhalingam Jegatheeswaran Joe Geraghty ajith k siriwardena Regional Hepato-Pancreato-Biliary Surgery Unit Manchester Royal InfirmaryOxford RoadManchester M139WLUK Department of Gastroenterology Manchester Royal InfirmaryOxford RoadManchester M139WLUK Faculty of Biology Medicine and HealthUniversity of ManchesterManchester M139PLUK

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 *** 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.

关键词： acute patients sustained

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

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Hepatobiliary & Pancreatic Diseases International 2022年第5期21卷 508-510页

作者： Santhalingam Jegatheeswaran Louise M Finch Maya C siriwardena ajith k siriwardena Regional Hepato-Pancreato-Biliary Surgery Unit Manchester Royal InfirmaryOxford RoadManchester M139WLUK Warwick Medical School WarwickUK Faculty of Biology Medicine and HealthUniversity of ManchesterManchesterUK

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.

关键词： pancreatitis acute terminology

Glucose metabolic phenotype of pancreatic cancer

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World Journal of Gastroenterology 2016年第12期22卷 3471-3485页

作者： Anthony kC Chan Jason IE Bruce ajith k siriwardena Regional Hepato-Pancreato-Biliary Surgery Unit Manchester Royal Infirmary Faculty of Life Sciences University of Manchester

AIM: To construct a global "metabolic phenotype" of pancreatic ductal adenocarcinoma(PDAC) reflecting tumour-related metabolic enzyme ***: 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.

关键词： Metabolism Pancreatic cancer Warburg effect Metabolic inhibitor Glycolysis krebs cycle

Quality of life assessment in patients with chronic pancreatitis receiving antioxidant therapy

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World Journal of Gastroenterology 2010年第32期16卷 4066-4071页

作者： Nehal S Shah Alistair J Makin Aali J Sheen ajith k siriwardena Hepatobiliary Surgery Unit Manchester Royal InfirmaryManchester M13 9WLUnited Kingdom Department of Gastroenterology Manchester Royal InfirmaryManchester M13 9WLUnited Kingdom

AIM:To undertake a baseline study comparing quality of life(QoL) in patients with chronic pancreatitis(CP) on Antox to those with CP,matched for disease duration,who were not on this ***:CP was defined according to the Zurich *** eight consecutive patients with CP who were taking Antox(antioxidants) were compared with 69 consecutive control CP patients not on *** Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core questions 30 and Pancreatic Modification(28 questions) were used to assess *** of a total of 137 patients 28 in each group were matched for disease duration(within 12 mo).Median disease duration was 8(1-22) years in the Antox group and 7(1-23) years in the Non-Antox cohort(P = NS,Mann-Whitney U-test).Other parameters(age,gender,etiology,endocrine and exocrine insufficiency) were similar between ***:Median visual analogue pain score in the Antox group was 3(0-8) compared with 6(0-8) in the Non-Antox group(P king,patients with CP taking antox had better scores than non-antox controls.

关键词： Chronic pancreatitis Antioxidants Quality of life Assessment Management