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ObjectivesKi-67, a marker of cellular proliferation, is associated with prognosis across a wide range of tumours, including gastroenteropancreatic neuroendocrine neoplasms (NENs), lymphoma, urothelial tumours and breast carcinomas. Its omission from the classification system of pulmonary NENs is controversial. This systematic review sought to assess whether Ki-67 is a prognostic biomarker in lung NENs and, if feasible, proceed to a meta-analysis.Research design and methodsMedline (Ovid), Embase, Scopus and the Cochrane library were searched for studies published prior to 28 February 2019 and investigating the role of Ki-67 in lung NENs. Eligible studies were those that included more than 20 patients and provided details of survival outcomes, namely, HRs with CIs according to Ki-67 percentage. Studies not available as a full text or without an English manuscript were excluded. This study was prospectively registered with PROSPERO.ResultsOf 11 814 records identified, seven studies met the inclusion criteria. These retrospective studies provided data for 1268 patients (693 TC, 281 AC, 94 large cell neuroendocrine carcinomas and 190 small cell lung carcinomas) and a meta-analysis was carried out to estimate a pooled effect. Random effects analyses demonstrated an association between a high Ki-67 index and poorer overall survival (HR of 2.02, 95% CI 1.16 to 3.52) and recurrence-free survival (HR 1.42; 95% CI 1.01 to 2.00).ConclusionThis meta-analysis provides evidence that high Ki-67 labelling indices are associated with poor clinical outcomes for patients diagnosed with pulmonary NENs. This study is subject to inherent limitations, but it does provide valuable insights regarding the use of the biomarker Ki-67, in a rare tumour.Prospero registration numberCRD42018093389.

IntroductionThe omission of the immunohistochemical proliferation marker Ki-67 labelling index (henceforth, simply Ki-67) from the 2015 WHO classification system of pulmonary neuroendocrine tumours (Lung-NETs) as a prognostic and grading criterion remains controversial. This systematic review along with meta-analysis will be conducted to assess the prognostic/grading utility of Ki-67 in Lung-NETs.MethodsThis systematic review will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. A systematic search of MEDLINE Ovid, Embase, Scopus and the Cochrane Library will be performed from the inception of each database to 28 February 2019 for studies investigating any role of Ki-67 in Lung-NETs. Only full papers published in English detailing survival outcomes and HRs according to Ki-67 will be included. The primary endpoint will be establishing whether Ki-67 is a reliable marker in determining prognosis and thus assessing grade of Lung-NETs patients.Ethics and disseminationEthical approval will not be required as this is an academic review of published literature. Findings will be disseminated through the preparation of a manuscript for publication in a peer-reviewed journal as well as presentation at national and international conferences.PROSPERO registration numberCRD42018093389

Pancreatic neuroendocrine tumors (PanNETs) are rare tumors but incidence is increasing. An increasing number of these tumors are diagnosed incidentally when they are small (<2 cm) and when patients are asymptomatic. The European Neuroendocrine Tumor Society (ENETS) recommends conservative watch and wait policy for these patients. However, best surgical approach (parenchyma-sparing or formal oncological resection) for these small tumors when surgery is indicated is currently unknown. Parenchyma-sparing resections such as enucleation is associated with higher risk of post-operative morbidity compared to formal oncological resections. They are also be associated with potentially inadequate surgical margin clearance and with lack of lymphadenectomy for full pathological staging.Method: This study is a retrospective study and the aim is to analyze pre-operative clinical predictors of nodal metastases for small PanNETs to identify which patients are at a lower risk of lymph node metastases and are therefore suitable for parenchyma-sparing resection.Conclusion: The primary endpoint of this study is to determine if pre-operative clinical predictors such as tumor size are associated with lymph node involvement in small PanNETs.

Pancreatic neuroendocrine tumours (PNET) is a rare disease and in the absence of metastases, surgical resection is recommended. Key factors affecting survival in PNETs are the stage and grade of the disease, but there is increasing evidence suggesting lymph node involvement is associated with shorter disease-free and overall survival. Ability to predict the likelihood of lymph node involvement at the time of diagnosis would affect surgical decision making in these patients. A systemic inflammatory index such as neutrophil to lymphocyte ratio or platelet to lymphocyte ratio has been associated with poor prognosis in several cancers.Method: This study is a retrospective multi-centre study. The data including pre-operative inflammatory markers such as haemoglobin, neutrophil, lymphocyte counts and pathological data including number of positive lymph nodes, tumour grade and size, are collected to assess the association between inflammatory index and lymph node involvement.Conclusion: This study aims to assess the value of routinely available pre-operative haematological markers in predicting lymph node involvement in non-functioning PNETs.

IntroductionCONTACT 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).MethodsThe 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.ResultsAmong 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).ConclusionPathways 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.

Background The clinico-oncological outcomes of precursor epithelial subtypes of adenocarcinoma arising from intraductal papillary mucinous neoplasms (A-IPMN) are limited to small cohort studies. Differences in recurrence patterns and response to adjuvant chemotherapy between A-IPMN subtypes are unknown. Methods Clincopathological features, recurrence patterns and long-term outcomes of patients undergoing pancreatic resection (2010–2020) for A-IPMN were reported from 18 academic pancreatic centres worldwide. Precursor epithelial subtype groups were compared using uni- and multivariate analysis. Results In total, 297 patients were included (median age, 70 years; male, 78.9%), including 54 (18.2%) gastric, 111 (37.3%) pancreatobiliary, 80 (26.9%) intestinal and 52 (17.5%) mixed subtypes. Gastric, pancreaticobiliary and mixed subtypes had comparable clinicopathological features, yet the outcomes were significantly less favourable than the intestinal subtype. The median time to recurrence in gastric, pancreatobiliary, intestinal and mixed subtypes were 32, 30, 61 and 33 months. Gastric and pancreatobiliary subtypes had worse overall recurrence ( p  = 0.048 and p  = 0.049, respectively) compared with the intestinal subtype but gastric and pancreatobiliary subtypes had comparable outcomes. Adjuvant chemotherapy was associated with improved survival in the pancreatobiliary subtype ( p  = 0.049) but not gastric ( p  = 0.992), intestinal ( p  = 0.852) or mixed subtypes ( p  = 0.723). In multivariate survival analysis, adjuvant chemotherapy was associated with a lower likelihood of death in pancreatobiliary subtype, albeit with borderline significance [hazard ratio (HR) 0.56; 95% confidence interval (CI) 0.31–1.01; p  = 0.058]. Conclusions Gastric, pancreatobiliary and mixed subtypes have comparable recurrence and survival outcomes, which are inferior to the more indolent intestinal subtype. Pancreatobiliary subtype may respond to adjuvant chemotherapy and further research is warranted to determine the most appropriate adjuvant chemotherapy regimens for each subtype.

Acute pancreatitis is a common surgical emergency. Identifying variations in presentation, incidence and management may assist standardisation and optimisation of care. The objective of the study was to document the current incidence management and outcomes of acute pancreatitis against international guidelines, and to assess temporal trends over the past 20 years. A prospective four-month audit of patients with acute pancreatitis was performed across the Wessex region. The Atlanta 2012 classifications were used to define cases, severity and complications. Outcomes were recorded using validated systems and correlated against guideline standards. Case ascertainment was validated with clinical coding and hospital episode statistics data. A total of 283 patient admissions with acute pancreatitis were identified. Aetiology included 153 gallstones (54%), 65 idiopathic (23%), 29 alcohol (10%), 9 endoscopic retrograde cholangiopancreatography (3%), 6 drug related (2%), 5 tumour (2%) and 16 other (6%). Compliance with guidelines had improved compared with our previous regional audit. Results were 6.5% mortality, 74% severity stratification, 23% idiopathic cases, 65% definitive treatment of gallstones within 2 weeks, 39% computed tomography within 6-10 days of severe pancreatitis presentation and 82% severe pancreatitis critical care admission. The Atlanta 2012 severity criteria significantly correlated with critical care stay, length of stay, development of complications and mortality (2% vs 6% vs 36%, < 0.0001). The incidence of acute pancreatitis in southern England has risen substantially. The Atlanta 2012 classification identifies patients with severe pancreatitis who have a high risk of fatal outcome. Acute pancreatitis management is seen to have evolved in keeping with new evidence and updated clinical guidelines.