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Background: The use of neoadjuvant therapy (NAT) in distal cholangiocarcinoma (dCCA) with regional arterial or extensive venous involvement, is not widely accepted and evidence is sparse., Aim: To synthesise evidence on NAT for dCCA and present the experience of a high-volume tertiary-centre managing dCCA with arterial involvement., Methods: A systematic review was performed according to PRISMA guidance to identify all studies reporting outcomes of patients with dCCA who received NAT. All patients from 2017 to 2022 who were referred for NAT for dCCA at our centre were retrospectively collected from a prospectively maintained database. Baseline characteristics, NAT type, progression to surgery and oncological outcomes were collected., Results: Twelve studies were included. The definition of "unresectable" locally advanced dCCA was heterogenous. Four studies reported outcomes for 9 patients who received NAT for dCCA with extensive vascular involvement. R0 resection rate ranged between 0 and 100% but without survival benefit in most cases. Remaining studies considered either NAT in resectable dCCA or inclusive with extrahepatic CCA. The presented case series includes 9 patients (median age 67, IQR 56-74 years, male:female 5:4) referred for NAT for borderline resectable or locally advanced disease. Three patients progressed to surgery and 2 were resected. One patient died at 14 months with evidence of recurrence at 6 months and the other died at 51 months following recurrence 6 months post-operatively., Conclusion: Evidence for benefit of NAT is limited. Consensus on criteria for uniform definition of resectability for dCCA is required. We propose using the established National-Comprehensive-Cancer-Network ® criteria for pancreatic ductal adenocarcinoma., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Pancreatic cancer, specifically pancreatic ductal adenocarcinoma (PDAC), continues to pose a significant clinical and scientific challenge. The most significant finding of recent years is that PDAC tumours harbour their specific microbiome, which differs amongst tumour entities and is distinct from healthy tissue. This review aims to evaluate and summarise all PDAC studies that have used the next-generation technique, 16S rRNA gene amplicon sequencing within each bodily compartment. As well as establishing a causal relationship between PDAC and the microbiome., Materials and Methods: This systematic review was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. A comprehensive search strategy was designed, and 1727 studies were analysed., Results: In total, 38 studies were selected for qualitative analysis and summarised significant PDAC bacterial signatures. Despite the growing amount of data provided, we are not able to state a universal 16S rRNA gene microbial signature that can be used for PDAC screening. This is most certainly due to the heterogeneity of the presentation of results, lack of available datasets and the intrinsic selection bias between studies., Conclusion: Several key studies have begun to shed light on causality and the influence the microbiome constituents and their produced metabolites could play in tumorigenesis and influencing outcomes. The challenge in this field is to shape the available microbial data into targetable signatures. Making sequenced data readily available is critical, coupled with the coordinated standardisation of data and the need for consensus guidelines in studies investigating the microbiome in PDAC., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Staging laparoscopy (SL) has become commonplace in the preoperative staging pathway for oesophagogastric (OG) cancer. SL is often performed before curative treatment to examine for macroscopic peritoneal metastases (PM) or positive peritoneal cytology (PPC). The aim of this study was to develop an objective risk scoring system to predict both PM and PPC at SL., Methods: A prospectively collected and maintained database of all OG cancer patients treated between 2006 and 2020 was reviewed. Univariate and multivariate analyses were performed to identify risk factors for both PM and PPC at SL. A risk score was produced for both PM and PPC, and then validated internally., Results: Among 968 patients who underwent SL, 96 (9.9%) had PM and 81 (8.4%) had PPC at SL. Tumour site ( p < 0.001), computed tomography (CT) T stage ( p < 0.001) and N stage ( p = 0.029) were significantly associated with PM at SL ( p < 0.001). Tumour site ( p < 0.001), biopsy histology ( p = 0.041), CT T stage ( p < 0.001) and N stage ( p < 0.001) were significantly associated with PPC. The risk scoring model for PM included cancer site and CT T stage. This was successfully tested on the validation set (area under the receiver operating characteristic [AUROC] = 0.730). The risk scoring model for PPC included cancer site, CT T and N stage. This was successfully tested on the validation set (AUROC = 0.773)., Conclusions: The current risk scores are valid tools with which to predict the risk PM and PPC in patients undergoing SL for OG cancer and may help to avoid subjecting patients to unnecessary SL.

Objective: The aim of the present study was to compare long-term post-resection oncological outcomes between A-IPMN and PDAC., Summary Background Data: Knowledge of long term oncological outcomes (e.g recurrence and survival data) comparing between adenocarcinoma arising from intraductal papillary mucinous neoplasms (A-IPMN) and pancreatic ductal adenocarcinoma (PDAC) is scarce., Methods: Patients undergoing pancreatic resection (2010-2020) for A-IPMN were identified retrospectively from 18 academic pancreatic centres and compared with PDAC patients from the same time-period. Propensity-score matching (PSM) was performed and survival and recurrence were compared between A-IPMN and PDAC., Results: 459 A-IPMN patients (median age,70; M:F,250:209) were compared with 476 PDAC patients (median age,69; M:F,262:214). A-IPMN patients had lower T-stage, lymphovascular invasion (51.4%vs. 75.6%), perineural invasion (55.8%vs. 71.2%), lymph node positivity (47.3vs. 72.3%) and R1 resection (38.6%vs. 56.3%) compared to PDAC(P<0.001). The median survival and time-to-recurrence for A-IPMN versus PDAC were 39.0 versus19.5months (P<0.001) and 33.1 versus 14.8months (P<0.001), respectively (median follow-up,78 vs.73 months). Ten-year overall survival for A-IPMN was 34.6%(27/78) and PDAC was 9%(6/67). A-IPMN had higher rates of peritoneal (23.0 vs. 9.1%, P<0.001) and lung recurrence (27.8% vs. 15.6%, P<0.001) but lower rates of locoregional recurrence (39.7% vs. 57.8%; P<0.001). Matched analysis demonstrated inferior overall survival (P=0.005), inferior disease-free survival (P=0.003) and higher locoregional recurrence (P<0.001) in PDAC compared to A-IPMN but no significant difference in systemic recurrence rates (P=0.695)., Conclusions: PDACs have inferior survival and higher recurrence rates compared to A-IPMN in matched cohorts. Locoregional recurrence is higher in PDAC but systemic recurrence rates are comparable and constituted by their own distinctive site-specific recurrence patterns., Competing Interests: Conflicts of interest: None, (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Untreated pancreatic exocrine insufficiency (PEI) results in substantial patient harm. Upper gastrointestinal surgery (bariatric metabolic surgery and oesophagogastric resection) affects the delicate physiology of pancreatic exocrine function and may result in PEI. The aim of this study was to assimilate the literature on incidence, diagnosis, and management of PEI after bariatric metabolic surgery and oesophagogastric resection., Methods: A systematic review of PubMed, MEDLINE, and Embase databases identified studies investigating PEI after non-pancreatic upper gastrointestinal surgery. Meta-analyses were undertaken for incidence of PEI and benefit of pancreatic enzyme replacement therapy., Results: Among 1620 patients from 24 studies included in quantitative synthesis, 36.0% developed PEI. The incidence of PEI was 23.0 and 50.4% after bariatric metabolic surgery and oesophagogastric resection respectively. Notably, the incidence of PEI was 44% after biliopancreatic diversion with duodenal switch and 66.2% after total gastrectomy. The most common diagnostic test used was faecal elastase 1 (15 of 31 studies), with less than 200 µg/g being diagnostic of PEI. A total of 11 studies considered the management of pancreatic exocrine insufficiency, with 78.6% of patients responding positively to pancreatic enzyme replacement when it was prescribed., Conclusion: PEI is common after non-pancreatic upper gastrointestinal surgery and patients may benefit from enzyme replacement therapy., (© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Surgical resection is a part of the treatment pathways for the management of pancreatic cancer with arterial involvement. Arterial resection in this context is however not widely supported due to the paucity and diversity of the reported evidence in the literature. The aim of this systematic review is the presentation and analysis of the current evidence in the field., Methods: A systematic literature search of PubMed, MEDLINE and the Cochrane Library was performed for eligible studies, following the PRISMA guidelines. Information on baseline characteristics, peri-operative outcomes, survival outcomes and histopathological findings were extracted for pooling and analysis., Results: Eight studies with a total of 170 patients were included in the analysis. One hundred and thirty-five patients had a pancreaticoduodenectomy (PD) and 35 had a total pancreatectomy (TP) with arterial resection. Perioperative morbidity was 43.5% and mortality was 4.5%. Median overall survival (OS) was 12.7 months (range, 10.5-22.2 months). Overall 3- and 5-year survival for this cohort was reported at 6.6% (range, 0-42.4%) and 3.3% (range, 0-6.6%) respectively. Resection margins were clear (R0) in a median of 75% of patients. Only a median of 45% of patients received neo-adjuvant chemotherapy., Conclusions: Arterial resection can be performed with an acceptable peri-operative morbidity and mortality. However, survival outcomes are still not convincing and future efforts should concentrate on patient and disease biology selection., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tgh.amegroups.com/article/view/10.21037/tgh-23-33/coif). The authors have no conflicts of interest to declare., (2023 Translational Gastroenterology and Hepatology. All rights reserved.)

Introduction: CONTACT is a national multidisciplinary study assessing the impact of the COVID-19 pandemic upon diagnostic and treatment pathways among patients with pancreatic ductal adenocarcinoma (PDAC)., Methods: The treatment of consecutive patients with newly diagnosed PDAC from a pre-COVID-19 pandemic cohort (07/01/2019-03/03/2019) were compared to a cohort diagnosed during the first wave of the UK pandemic ('COVID' cohort, 16/03/2020-10/05/2020), with 12-month follow-up., Results: Among 984 patients (pre-COVID: n = 483, COVID: n = 501), the COVID cohort was less likely to receive staging investigations other than CT scanning (29.5% vs. 37.2%, p = 0.010). Among patients treated with curative intent, there was a reduction in the proportion of patients recommended surgery (54.5% vs. 76.6%, p = 0.001) and increase in the proportion recommended upfront chemotherapy (45.5% vs. 23.4%, p = 0.002). Among patients on a non-curative pathway, fewer patients were recommended (47.4% vs. 57.3%, p = 0.004) or received palliative anti-cancer therapy (20.5% vs. 26.5%, p = 0.045). Ultimately, fewer patients in the COVID cohort underwent surgical resection (6.4% vs. 9.3%, p = 0.036), whilst more patients received no anti-cancer treatment (69.3% vs. 59.2% p = 0.009). Despite these differences, there was no difference in median overall survival between the COVID and pre-COVID cohorts, (3.5 (IQR 2.8-4.1) vs. 4.4 (IQR 3.6-5.2) months, p = 0.093)., Conclusion: Pathways for patients with PDAC were significantly disrupted during the first wave of the COVID-19 pandemic, with fewer patients receiving standard treatments. However, no significant impact on survival was discerned., (© 2023. The Author(s).)

Background: Symptomatic gallstones are common. Ursodeoxycholic acid (UDCA) is a bile acid that dissolves gallstones. There is increasing interest in UDCA for symptomatic gallstones, particularly in those unfit for surgery., Method: A UK clinician survey of use and opinions about UDCA in symptomatic gallstones was performed, assessing clinicians' beliefs and perceptions of UDCA effectiveness. A systematic review was performed in accordance with the PRISMA guidelines. PubMed, MEDLINE, and Embase databases were searched for studies of UDCA for symptomatic gallstones (key terms included 'ursodeoxycholic acid'; 'UDCA'; 'biliary pain'; and 'biliary colic'). Information was assessed by two authors, including bias assessment, with independent review of conflicts., Results: Overall, 102 clinicians completed the survey, and 42 per cent had previous experience of using UDCA. Survey responses demonstrated clinical equipoise surrounding the benefit of UDCA for the management of symptomatic gallstones, with no clear consensus for benefit or non-benefit; however, 95 per cent would start using UDCA if there was a randomized clinical trial (RCT) demonstrating a benefit. Eight studies were included in the review: four RCTs, three prospective studies, and one retrospective study. Seven of eight studies were favourable of UDCA for biliary pain. Outcomes and follow-up times were heterogenous, as well as comparator type, with only four of eight studies comparing with placebo., Conclusion: Evidence for UDCA in symptomatic gallstones is scarce and heterogenous. Clinicians currently managing symptomatic gallstone disease are largely unaware of the benefit of UDCA, and there is clinical equipoise surrounding the benefit of UDCA. Level 1 evidence is required by clinicians to support UDCA use in the future., (© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd.)

Introduction: The SARS-CoV-2 pandemic presented healthcare providers with an extreme challenge to provide cancer services. The impact upon the diagnostic and treatment capacity to treat pancreatic cancer is unclear. This study aimed to identify national variation in treatment pathways during the pandemic., Methods: A survey was distributed to all United Kingdom pancreatic specialist centres, to assess diagnostic, therapeutic and interventional services availability, and alterations in treatment pathways. A repeating methodology enabled assessment over time as the pandemic evolved., Results: Responses were received from all 29 centres. Over the first six weeks of the pandemic, less than a quarter of centres had normal availability of diagnostic pathways and a fifth of centres had no capacity whatsoever to undertake surgery. As the pandemic progressed services have gradually improved though most centres remain constrained to some degree. One third of centres changed their standard resectable pathway from surgery-first to neoadjuvant chemotherapy. Elderly patients, and those with COPD were less likely to be offered treatment during the pandemic., Conclusion: The COVID-19 pandemic has affected the capacity of the NHS to provide diagnostic and staging investigations for pancreatic cancer. The impact of revised treatment pathways has yet to be realised., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Many studies have explored factors relating to post-operative pancreatic fistula (POPF); however, the original definition (All-POPF) was revised to include only 'clinically relevant' (CR) POPF. This study identified variables associated with the two International Study Group on Pancreatic Surgery definitions to identify which variables are more strongly associated with CR-POPF., Methods: A systematic review identified all studies reporting risk factors for POPF (using both International Study Group on Pancreatic Fistula definitions) following pancreatoduodenectomy. The primary outcome was factors associated with CR-POPF. Meta-analyses (random effects models) of pre-, intra- and post-operative factors associated with POPF in more than two studies were included., Results: Among 52 774 patients All-POPF (n = 69 studies) and CR-POPF (n = 53 studies) affected 27% (95% confidence interval (CI 95% ) 23-30) and 19% (CI 95% 17-22), respectively. Of the 176 factors, 24 and 17 were associated with All- and CR-POPF, respectively. Absence of pre-operative pancreatitis, presence of renal disease, no pre-operative neoadjuvant therapy, use of post-operative somatostatin analogues, absence of associated venous or arterial resection were associated with CR-POPF but not All-POPF., Conclusion: In conclusion this study demonstrates wide variation in reported rates of POPF and that several risk factors associated with CR-POPF are not used within risk prediction models. Data from this study can be used to shape future studies, research and audit across ethnic and geographic boundaries in POPF following pancreatoduodenectomy., (© 2020 Royal Australasian College of Surgeons.)

Bochdalek hernias rarely contain an intrathoracic kidney, and there are few reports of their operative repair. A woman presented with progressive dyspnoea limiting her quality of life. Imaging showed a Bochdalek hernia containing omentum, large bowel and the left kidney. The woman was unexpectedly admitted to the intensive care unit with respiratory failure secondary to gallstone pancreatitis whilst awaiting elective repair of her hernia. Surgical repair of the hernia was performed via laparotomy with cholecystectomy to treat both problems. The woman recovered well and is independently mobile without any exertional dyspnoea.

Background: Lung resection remains the gold standard treatment for early stage lung cancer; prediction of postoperative lung function is a key selection criterion for surgery with the aim of determining risk of postoperative dyspnoea. We aimed to identify the different prediction techniques used, and compare their accuracy., Methods: A systematic review and meta-analysis sought to synthesise studies conducted that assess prediction of postoperative lung function up to 18/02/2018 (n = 135). PROBAST was used to assess risk of bias in studies, 17 studies were judged to be at low risk of bias., Findings: Meta-analysis revealed CT volume and density measurement to be the most accurate (mean difference 71 ml) and precise (standard deviation 207 ml) of the reported techniques used for predicting FEV1; evidence for predicting gas transfer was lacking., Interpretation: The evidence suggests using CT volume and density is the preferred technique in the prediction of postoperative FEV1. Further studies are required to ensure that the methods and thresholds we propose are linked to patient reported outcomes., Funding: Salary support for NKO, RM, PN, BN, and AMT was provided by University Hospitals Birmingham NHS Foundation Trust., Competing Interests: AMT reports grants from Grifols Biotherapeutics, grants from Alpha-1 Foundation, personal fees from CSL Behring, grants and non-financial support from Arrowhead Inc, outside the submitted work. NKO, JH-S, RM, PN, and BN have no conflict of interest to declare., (© 2019 Published by Elsevier Ltd.)

Background: Mortality following lung cancer resection has been shown to double between 30 and 90 days and readmission following surgery is associated with an increased risk of mortality. The aim of this study was to describe the causes of readmission and mortality and enable the identification of potentially modifiable factors associated with these events., Methods: Prospective cohort study at a United Kingdom tertiary referral centre conducted over 55 months. Binary logistic regression was used to identify factors associated with death within 90 days of surgery., Results: The 30 day and 90 day mortality rates were 1.4% and 3.3% respectively. The most common causes of death were pneumonia, lung cancer and Acute Respiratory Distress Syndrome/Multi Organ Failure. Potentially modifiable risk factors for death identified were: Postoperative pulmonary complications (Odds ratio 6.1), preoperative lymphocyte count (OR 0.25), readmission within 30 days (OR 4.2) and type of postoperative analgesia (OR for intrathecal morphine 4.8). The most common causes of readmission were pneumonia, shortness of breath and pain., Conclusions: Postoperative mortality is not simply due to fixed factors; the impacts of age, gender and surgical procedure on postoperative survival are reduced when the postoperative course of recovery is examined. Perioperative immune function, as portrayed by the occurrence of infection and lower lymphocyte count in the immediate perioperative period, and pain control method are strongly associated with 90 day mortality; further studies in these fields are indicated as are studies of psychological factors in recovery., Clinical Registration Number: ISRCTN00061628., (Copyright © 2019. Published by Elsevier Ltd.)