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Pancreatic cancer still has one of the worst prognoses of all solid malignancies, despite developments in cancer knowledge and care. Research into pancreatic cancer has not fully translated into clinical improvements and as a result, fewer than 1% of patients survive 10 years post-diagnosis. This bleak outlook for patients could be improved by earlier diagnosis. The human erythrocyte phosphatidylinositol glycan class A (PIG-A) assay monitors the mutation status of the X-linked PIG-A gene by measuring glycosyl phosphatidylinositol (GPI)-anchored proteins on the extracellular surface. We have previously identified an elevated PIG-A mutant frequency in oesophageal adenocarcinoma patients and here investigate whether this could be seen in a pancreatic cancer cohort, given the urgent need for novel pancreatic cancer biomarkers. In our pilot study, an elevated PIG-A mutant frequency (5.775 × 10−6 (95% CI 4.777–10) mutants per million) was seen in pancreatic cancer patients (n = 30) when compared to the non-cancer control group (n = 14) who had an erythrocyte mutant frequency of 4.211 × 10−6 (95% CI 1.39–5.16) mutants per million (p = 0.0052). A cut-off value of 4.7 mutants per million provided an AUROC of 0.7595 with a sensitivity of 70% and specificity of 78.57%. A secondary measure of DNA damage in an alternative blood cell population also showed an increase in peripheral lymphocytes using the cytokinesis-block micronucleus assay (p = 0.0164) (AUROC = 0.77, sensitivity = 72.22%, specificity = 72.73%). The micronucleus frequency and PIG-A status show some potential as blood-based biomarkers of pancreatic cancer, but further investigations of these DNA damage tests are required to assess their utility in pancreatic cancer diagnosis.

Background: Gallbladder cancer (GBC) is rare but aggressive. The extent of surgical intervention for different GBC stages is non-uniform, ranging from cholecystectomy alone to extended resections including major hepatectomy, resection of adjacent organs and routine extrahepatic bile duct resection (EBDR). Robust evidence here is lacking, however, and survival benefit poorly defined. This study assesses factors associated with recurrence-free survival (RFS), overall survival (OS) and morbidity and mortality following GBC surgery in high income countries (HIC) and low and middle income countries (LMIC). Methods: The multicentre, retrospective Operative Management of Gallbladder Cancer (OMEGA) cohort study included all patients who underwent GBC resection across 133 centres between 1st January 2010 and 31st December 2020. Regression analyses assessed factors associated with OS, RFS and morbidity. Findings: On multivariable analysis of all 3676 patients, wedge resection and segment IVb/V resection failed to improve RFS (HR 1.04 [0.84–1.29], p = 0.711 and HR 1.18 [0.95–1.46], p = 0.13 respectively) or OS (HR 0.96 [0.79–1.17], p = 0.67 and HR 1.48 [1.16–1.88], p = 0.49 respectively), while major hepatectomy was associated with worse RFS (HR 1.33 [1.02–1.74], p = 0.037) and OS (HR 1.26 [1.03–1.53], p = 0.022). Furthermore, EBDR (OR 2.86 [2.3–3.52], p < 0.0010), resection of additional organs (OR 2.22 [1.62–3.02], p < 0.0010) and major hepatectomy (OR 3.81 [2.55–5.73], p < 0.0010) were all associated with increased morbidity and mortality. Compared to LMIC, patients in HIC were associated with poorer RFS (HR 1.18 [1.02–1.37], p = 0.031) but not OS (HR 1.05 [0.91–1.22], p = 0.48). Adjuvant and neoadjuvant treatments were infrequently used. Interpretation: In this large, multicentre analysis of GBC surgical outcomes, liver resection was not conclusively associated with improved survival, and extended resections were associated with greater morbidity and mortality without oncological benefit. Aggressive upfront resections do not benefit higher stage GBC, and international collaborations are needed to develop evidence-based neoadjuvant and adjuvant treatment strategies to minimise surgical morbidity and prioritise prognostic benefit. Funding:Cambridge Hepatopancreatobiliary Department Research Fund.

Background Oncological outcomes are comparable between octogenarians and younger patients after pancreatoduodenectomy for pancreatic ductal adenocarcinoma Methods A multicentre case-control study of octogenarians matched on complexity of surgery with consecutive younger controls who underwent PD for PDAC (2008–2017). Results Some 220 patients were included, 110 octogenarians (age 81 (80–83)) and 110 controls (age 69 (62–74)). Charlson Comorbidity Index score was higher in octogenarians than controls (7 (6–8) vs 5 (4–6)), p Conclusions In selected fit octogenarians, equivalent survival is achievable. Centralisation and multimodal therapy are key. Pre-operative risk stratification using at ECOG and albumin level can be used to identify an appropriate population.

We recently published in GUT the outcomes of acute pancreatitis (AP) and coexisting SARS-CoV-2 infection.1 A number of patients who were SARS-CoV-2 positive had AP of unknown aetiology (25%) speculating SARS-CoV-2 as a cause for AP similar to other viruses.2 However, most patients did not complete investigations to exclude other causes of AP. In addition, SARS-CoV-2 infection may cause aberrant glycometabolic control,3 however it is unknown if this increases the risk of long-term diabetes mellitus (DM). The follow-up data were collected 12 months from the date of recruitment for 1476 patients (118 patients who were SARS-CoV-2 positive and 1358 patients who were negative) to establish an aetiology for AP and development of DM. Among the 118 patients who were SARS-CoV-2 positive, 35 patients had idiopathic or unknown aetiology AP. Sixteen patients underwent either MRCP (n=13) or EUS (n=4) and the remaining patients underwent biochemical investigations to exclude other causes of AP. The final aetiology of AP was available for 83 (70.3%) patients and included gallstones (56, 47.4%), alcohol (19, 16.1%), post ERCP (2, 1.7%) and other (6, 5.1%). Overall, 23 patients had a change of aetiology, and in 35 (29.7%) patients AP was considered idiopathic. Patients who were SARS-CoV-2 positive were more likely to have idiopathic AP (34.7% vs 13.9%, p

Background Pancreatoduodenectomy (PD) is frequently the surgical treatment indicated for a number of pathologies. Elderly patients may be denied surgery because of concerns over poor perioperative outcomes. The aim of this study was to evaluate postoperative clinical outcomes and provide evidence on current UK practice in the elderly population after PD. Methods This was a multicentre retrospective case–control study of octogenarians undergoing PD between January 2008 and December 2017, matched with younger controls from seven specialist centres in the UK. The primary endpoint was 90-day mortality. Secondary endpoints were index admission mortality, postoperative complications, and 30-day readmission rates. Results In total, 235 octogenarians (median age 81 (range 80–90) years) and 235 controls (age 67 (31–79) years) were included in the study. Eastern Cooperative Oncology Group performance status (median 0 (range 0–3) versus 0 (0–2); P = 0.010) and Charlson Co-morbidity Index score (7 (6–11) versus 5 (2–9); P = 0.001) were higher for octogenarians than controls. Postoperative complication and 30-day readmission rates were comparable. The 90-day mortality rate was higher among octogenarians (9 versus 3 per cent; P = 0.030). Index admission mortality rates were comparable (4 versus 2 per cent; P = 0.160), indicating that the difference in mortality was related to deaths after hospital discharge. Despite the higher 90-day mortality rate in the octogenarian population, multivariable Cox regression analysis did not identify age as an independent predictor of postoperative mortality. Conclusion Despite careful patient selection and comparable index admission mortality, 90-day and, particularly, out-of-hospital mortality rates were higher in octogenarians.

The centralisation of pancreatic cancer (PC) services still varies worldwide. This study aimed to assess the impact that a centralisation has had on patients in South Wales, UK. A retrospective cohort analysis of patients in South Wales, UK, with PC prior to (2004–2009), and after (2010–2014) the formation of a specialist centre. Patients were identified using record linkage of electronic health records. The overall survival (OS) of all 3413 patients with PC increased from a median (IQR) 10 weeks (3–31) to 11 weeks (4–35), p = 0.038, after centralisation. The OS of patients undergoing surgical resection or chemotherapy alone did not improve (93 weeks (39–203) vs. 90 weeks (50–95), p = 0.764 and 33 weeks (20–57) vs. 33 weeks (19–58), p = 0.793). Surgical resection and chemotherapy rates increased (6.1% vs. 9.2%, p

Item does not contain fulltext BACKGROUND: A radical left pancreatectomy in patients with pancreatic ductal adenocarcinoma (PDAC) may require extended, multivisceral resections. The role of a laparoscopic approach in extended radical left pancreatectomy (ERLP) is unclear since comparative studies are lacking. The aim of this study was to compare outcomes after laparoscopic vs open ERLP in patients with PDAC. METHODS: An international multicenter propensity-score matched study including patients who underwent either laparoscopic or open ERLP (L-ERLP; O-ERLP) for PDAC was performed (2007-2015). The ISGPS definition for extended resection was used. Primary outcomes were overall survival, margin negative rate (R0), and lymph node retrieval. RESULTS: Between 2007 and 2015, 320 patients underwent ERLP in 34 centers from 12 countries (65 L-ERLP vs. 255 O-ERLP). After propensity-score matching, 44 L-ERLP could be matched to 44 O-ERLP. In the matched cohort, the conversion rate in L-ERLP group was 35%. The L-ERLP R0 resection rate (matched cohort) was comparable to O-ERLP (67% vs 48%; P = 0.063) but the lymph node yield was lower for L-ERLP than O-ERLP (median 11 vs 19, P = 0.023). L-ERLP was associated with less delayed gastric emptying (0% vs 16%, P = 0.006) and shorter hospital stay (median 9 vs 13 days, P = 0.005), as compared to O-ERLP. Outcomes were comparable for additional organ resections, vascular resections (besides splenic vessels), Clavien-Dindo grade ≥ III complications, or 90-day mortality (2% vs 2%, P = 0.973). The median overall survival was comparable between both groups (19 vs 20 months, P = 0.571). Conversion did not worsen outcomes in L-ERLP. CONCLUSION: The laparoscopic approach may be used safely in selected patients requiring ERLP for PDAC, since morbidity, mortality, and overall survival seem comparable, as compared to O-ERLP. L-ERLP is associated with a high conversion rate and reduced lymph node yield but also with less delayed gastric emptying and a shorter hospital stay, as compared to O-ERLP.

Introduction Emerging evidence revealed the active role played by capillary morphogenesis gene 2 (CMG2) during the disease progression and metastasis of some cancers. It was shown that CMG2 was increased in pancreatic tumours in our previous research. The current study further validated this finding for the expression of CMG2 in pancreatic cancer and also dissected its clinical implication. Method Immunochemical staining of CMG2 was performed on a pancreatic cancer tissue microarray (PA2081, Biomax, n = 104). Clinical relevance of CMG2 was analysed in TCGA pancreatic cancer cohort and gene array data (GSE71729) using ANOVA and Kaplan-Meier analyses. Influence of CMG2 on adhesion to a mesothelial cell monolayer was determined using both Mia-PaCa-2 and PANC-1 cell lines with CMG2 knockdown. Result CMG2 is increased significantly in pancreatic ductal adenomas, P Conclusion Elevated CMG2 expression in pancreatic ductal adenocarcinomas is associated with distant metastasis and shorter survival which requires further investigation to shed light on its therapeutic potential. Take-home Message Elevated CMG2 expression in pancreatic ductal adenocarcinomas is associated with distant metastasis and shorter survival.

Kidins220 is a transmembrane scaffold protein involved in several types of cancer. The aim of the present study was to examine the role of Kidins220 in tumorigenesis and disease progression of pancreatic cancer. The relevant signalling pathways including EGFR, EMT, and MMP were also investigated. The expression of Kidins220 was examined at the transcript and protein level. The Kidins220 knockdown cell model was established and its influence on cellular functions was determined. Involvement of Kidins220 in tumorigenesis and metastasis was examined in CD1 mice, respectively. The results showed that, reduced Kidin220 expression was associated with tumorigenesis, metastasis, and overall survival of pancreatic cancer. Knockdown of Kidins220 promoted proliferation, colony formation and tumorigenic capacity of pancreatic cancer cells in vitro and in vivo, respectively. Kidins220 regulated pancreatic cancer cell migration through the EGFR/AKT/ERK signalling pathway. Furthermore, enhanced EMT was observed in the pancreatic cancer cell lines with the knockdown of Kidins220, underlying EGFR regulation. Kidins220 also affected cell invasion via MMP1. A reduced expression of Kidins220 was observed in pancreatic cancer, which is associated with disease progression, distant metastasis and poor prognosis. The loss of Kidins220 in pancreatic cancer may contribute to disease progression through the upregulation of EGFR and downstream signalling.

Background Recently, the first randomized trials comparing minimally invasive distal pancreatectomy (MIDP) with open distal pancreatectomy (ODP) for non-malignant and malignant disease showed a 2-day reduction in time to functional recovery after MIDP. However, for pancreatic ductal adenocarcinoma (PDAC), concerns have been raised regarding the oncologic safety (i.e., radical resection, lymph node retrieval, and survival) of MIDP, as compared to ODP. Therefore, a randomized controlled trial comparing MIDP and ODP in PDAC regarding oncological safety is warranted. We hypothesize that the microscopically radical resection (R0) rate is non-inferior for MIDP, as compared to ODP. Methods/design DIPLOMA is an international randomized controlled, patient- and pathologist-blinded, non-inferiority trial performed in 38 pancreatic centers in Europe and the USA. A total of 258 patients with an indication for elective distal pancreatectomy with splenectomy because of proven or highly suspected PDAC of the pancreatic body or tail will be randomly allocated to MIDP (laparoscopic or robot-assisted) or ODP in a 1:1 ratio. The primary outcome is the microscopically radical resection margin (R0, distance tumor to pancreatic transection and posterior margin ≥ 1 mm), which is assessed using a standardized histopathology assessment protocol. The sample size is calculated with the following assumptions: 5% one-sided significance level (α), 80% power (1-β), expected R0 rate in the open group of 58%, expected R0 resection rate in the minimally invasive group of 67%, and a non-inferiority margin of 7%. Secondary outcomes include time to functional recovery, operative outcomes (e.g., blood loss, operative time, and conversion to open surgery), other histopathology findings (e.g., lymph node retrieval, perineural- and lymphovascular invasion), postoperative outcomes (e.g., clinically relevant complications, hospital stay, and administration of adjuvant treatment), time and site of disease recurrence, survival, quality of life, and costs. Follow-up will be performed at the outpatient clinic after 6, 12, 18, 24, and 36 months postoperatively. Discussion The DIPLOMA trial is designed to investigate the non-inferiority of MIDP versus ODP regarding the microscopically radical resection rate of PDAC in an international setting. Trial registration ISRCTN registry ISRCTN44897265. Prospectively registered on 16 April 2018.

OBJECTIVE To compare short-term clinical outcomes after Kimura and Warshaw minimally invasive distal pancreatectomy (MIDP). BACKGROUND Spleen preservation during distal pancreatectomy can be achieved by either preservation (Kimura) or resection (Warshaw) of the splenic vessels. Multicenter studies reporting outcomes of Kimura and Warshaw spleen-preserving MIDP are scarce. METHODS Multicenter retrospective study including consecutive MIDP procedures intended to be spleen-preserving from 29 high-volume centers (≥15 distal pancreatectomies annually) in eight European countries. Primary outcomes were secondary splenectomy for ischemia and major (Clavien-Dindo grade ≥III) complications. Sensitivity analysis assessed the impact of excluding ('rescue') Warshaw procedures which were performed in centers that typically (>75%) performed Kimura MIDP. RESULTS Overall, 1095 patients after MIDP were included with successful splenic preservation in 878 patients (80%), including 634 Kimura and 244 Warshaw procedures. Rates of clinically relevant splenic ischemia (0.6% vs. 1.6%, p = 0.127) and major complications (11.5% vs 14.4%, p = 0.308) did not differ significantly between Kimura and Warshaw MIDP, respectively. Mortality rates were higher after Warshaw MIDP (0.0% vs. 1.2%, p = 0.023), and decreased in the sensitivity analysis (0.0% vs 0.6%, p = 0.052). Kimura MIDP was associated with longer operative time (202 vs 184 min, p = 0.033) and less blood loss (100 vs 150 ml, p < 0.001) as compared to Warshaw MIDP. Unplanned splenectomy was associated with a higher conversion rate (20.7% vs 5.0%, p < 0.001). CONCLUSION Kimura and Warshaw spleen-preserving MIDP provide equivalent short-term outcomes with low rates of secondary splenectomy and postoperative morbidity. Further analyses of long-term outcomes are needed.

Introduction: Ampullary adenocarcinoma (AAC) is a rare malignancy with great morphological heterogeneity, which complicates the prediction of survival and, therefore, clinical decision-making. The aim of this study was to develop and externally validate a prediction model for survival after resection of AAC. Materials and methods: An international multicenter cohort study was conducted, including patients who underwent pancreatoduodenectomy for AAC (2006–2017) from 27 centers in 10 countries spanning three continents. A derivation and validation cohort were separately collected. Predictors were selected from the derivation cohort using a LASSO Cox proportional hazards model. A nomogram was created based on shrunk coefficients. Model performance was assessed in the derivation cohort and subsequently in the validation cohort, by calibration plots and Uno's C-statistic. Four risk groups were created based on quartiles of the nomogram score. Results: Overall, 1007 patients were available for development of the model. Predictors in the final Cox model included age, resection margin, tumor differentiation, pathological T stage and N stage (8th AJCC edition). Internal cross-validation demonstrated a C-statistic of 0.75 (95% CI 0.73–0.77). External validation in a cohort of 462 patients demonstrated a C-statistic of 0.77 (95% CI 0.73–0.81). A nomogram for the prediction of 3- and 5-year survival was created. The four risk groups showed significantly different 5-year survival rates (81%, 57%, 22% and 14%, p < 0.001). Only in the very-high risk group was adjuvant chemotherapy associated with an improved overall survival. Conclusion: A prediction model for survival after curative resection of AAC was developed and externally validated. The model is easily available online via www.pancreascalculator.com.

Introduction: \ud 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.\ud \ud Methods: \ud 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.\ud \ud Results: \ud 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.\ud \ud Conclusion: \ud 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.

Guidelines advocate minimally invasive drainage rather than open surgery for infected pancreatic necrosis (IPN) after acute pancreatitis. We hypothesized that the conservative approach could be extended even further by treating patients using an antibiotics-only protocol.Between June 2009 and July 2017, patients with IPN were selectively managed with carbapenem antibiotics for a minimum of 6 weeks. We compared these patients with patients who underwent minimal access retroperitoneal pancreatic necrosectomy (MARPN) for IPN to identify characteristics of this patient group.Of 33 patients with radiologically proven IPN, 13 patients received antibiotics without any surgical or radiological intervention and resulted in no disease-specific mortality and one case of pancreatic insufficiency. In comparison, 44 patients underwent MARPN with a mortality of 20%, and 81.8% developed pancreatic insufficiency. The modified Glasgow score and computed tomography severity score was less in the antibiotic-only group (P0.001 and P=0.014, respectively). Patients who underwent MARPN had lower serum haemoglobin and albumin levels (P=0.030 and 0.001, respectively), and a higher C-reactive protein (P=0.027).Conservative treatment of IPN with antibiotics is a valid management option for haemodynamically stable patients experiencing less severe disease, requiring careful selection by experienced clinicians.

The neutrophil-to-lymphocyte ratio (NLR) is thought to reflect cancer disease burden. To assess the prognostic ability of the NLR on overall survival in patients with resectable, pancreatic cancer a meta-analysis of published literature was undertaken.A systematic review was performed independently by two authors using PubMed, Ovid MEDLINE and Embase databases. Included studies detailed the pre-operative NLR and overall survival of pancreatic cancer patients.Of the 214 studies retrieved using the search strategy, 8 studies involving 1519 patients were included in the meta-analysis. Only one study did not find a statistically significant association between a high NLR and OS. The pooled Hazard Ratio was 1.77 (95% CI [1.45-2.15]; p0.01). The NLR cut-off values ranged from 2 to 5. There was low to moderate inter-study heterogeneity (IA high pre-operative NLR indicates a worse prognosis than in patients with a low NLR. There is potential to use the NLR to direct therapies. A specific cut-off value has not been established from this study and so further research is required.

Aims: The aim of this bibliometric analysis was to identify the main topics and publications that have enhanced our understanding and influenced the management of intraductal papillary mucinous neoplasm (IPMN). Methods: The Thompson Reuters Web of Science database was searched using the terms 'Intraductal papillary mucinous neoplasm', or 'IPMN' to identify all English language manuscripts for the study. The 100 most cited articles were further analyzed by journal, topic, year, author and institution. Results: Results: Total 2,833 eligible manuscripts were identified. The median (range) citation number was 129 (93–1006). The most cited paper presented consensus guidelines regarding the management of IPMN (1006 citations). The Annals of Surgery published the highest number of manuscripts (n = 13) and subsequently had the highest number of citations (n = 2889). The USA published most manuscripts within the top 100 (n = 46). The most discussed topic was IPMN management (n = 29), incorporating diagnosis and surgery. The second most commonly discussed topic was histology (n = 18). Conclusion: This bibliometric analysis highlights how advances in the histological evaluation of IPMN have influenced current management strategies for IPMN. This manuscript highlights the most cited and influential references related to IPMN and serves as a guide to the most popular IPMN research themes.

Whether patients who undergo resection of ampullary adenocarcinoma have a survival benefit from adjuvant chemotherapy is currently unknown. The aim of this study was to compare survival between patients with and without adjuvant chemotherapy after resection of ampullary adenocarcinoma in a propensity score-matched analysis.An international multicentre cohort study was conducted, including patients who underwent pancreatoduodenectomy for ampullary adenocarcinoma between 2006 and 2017, in 13 centres in six countries. Propensity scores were used to match patients who received adjuvant chemotherapy with those who did not, in the entire cohort and in two subgroups (pancreatobiliary/mixed and intestinal subtypes). Survival was assessed using the Kaplan-Meier method and Cox regression analyses.Overall, 1163 patients underwent pancreatoduodenectomy for ampullary adenocarcinoma. After excluding 187 patients, median survival in the remaining 976 patients was 67 (95 per cent c.i. 56 to 78) months. A total of 520 patients (53·3 per cent) received adjuvant chemotherapy. In a propensity score-matched cohort (194 patients in each group), survival was better among patients who received adjuvant chemotherapy than in those who did not (median survival not reached versus 60 months respectively; P = 0·051). A survival benefit was seen in patients with the pancreatobiliary/mixed subtype; median survival was not reached in patients receiving adjuvant chemotherapy and 32 months in the group without chemotherapy (P = 0·020). Patients with the intestinal subtype did not show any survival benefit from adjuvant chemotherapy.Patients with resected ampullary adenocarcinoma may benefit from gemcitabine-based adjuvant chemotherapy, but this effect may be reserved for those with the pancreatobiliary and/or mixed subtype.Actualmente se desconoce si la quimioterapia adyuvante ofrece un beneficio en la supervivencia de los pacientes que se someten a resección de un adenocarcinoma ampular. El objetivo de este estudio fue comparar la supervivencia mediante la concordancia estimada por emparejamiento por puntaje de propensión, entre pacientes con y sin quimioterapia adyuvante después de la resección de un adenocarcinoma ampular. MÉTODOS: Se realizó un estudio internacional de cohortes multicéntrico, que incluyó a los pacientes que se sometieron a una duodenopancreatectomía por adenocarcinoma ampular (2006-2017) en 13 centros de seis países. Los puntajes de propensión se usaron para emparejar a los pacientes que recibieron quimioterapia adyuvante con los que no; tanto en la cohorte completa como en dos subgrupos (subtipo pancreaticobiliar / mixto e intestinal). La supervivencia se evaluó utilizando el método de Kaplan-Meier y las regresiones de Cox.En total, 1.163 pacientes fueron sometidos a una duodenopancreatectomía por adenocarcinoma ampular. Después de excluir a 179 pacientes, la mediana de supervivencia de los 976 pacientes restantes fue de 67 meses (i.c. del 95%, 56-78), de los cuales un total de 520 pacientes (53%) recibieron quimioterapia adyuvante. En una cohorte de emparejamiento por puntaje de propensión (194 versus 194 pacientes), la mediana de supervivencia fue mejor en los pacientes tratados con quimioterapia adyuvante en comparación con aquellos sin quimioterapia adyuvante (no se alcanzó la mediana de supervivencia versus 60 meses, respectivamente; P = 0,051). En el subtipo pancreaticobiliar/mixto se observó un beneficio en la supervivencia; no se alcanzó la mediana de supervivencia en pacientes que recibieron quimioterapia adyuvante versus 32 meses en el grupo sin quimioterapia, P = 0,020. El subtipo intestinal no mostró beneficio en la supervivencia de la quimioterapia adyuvante. CONCLUSIÓN: Los pacientes con adenocarcinoma ampular resecado pueden beneficiarse de la quimioterapia adyuvante basada en gemcitabina, pero este efecto podría reservarse para aquellos pacientes con subtipo de tumor pancreaticobiliar y/o mixto.

Background Pancreaticoduodenectomy is often required in patients with duodenal adenoma and adenocarcinoma and these patients generally have soft pancreatic texture and small pancreatic ducts, the two most significant factors associated with post-operative pancreatic fistula (POPF). The aims of the study were to evaluate the rate of POPF and long-term outcomes for patients with duodenal adenoma and adenocarcinoma who underwent curative resection. Methods This retrospective study (2004-2014) examined patients treated surgically with non-ampullary duodenal tumours (NADTs) in two hepatopancreaticobiliary units in Victoria, Australia, and Swansea, UK. Results There were 49 resections performed including 33 pancreaticoduodenectomies, five pancreas-preserving total duodenectomies and 11 segmental duodenal resections. Median length of follow-up was 23.5 months. Final histopathology revealed 18 duodenal adenomas and 31 adenocarcinomas. POPF rate for NADTs was 28.9% (of which 54.5% were grade C) compared to 14.5% for all other pathologies. Grade C POPF was associated with poorer survival outcomes (hazard ratio = 6.73; P = 0.005). The 5-year overall survival for patients with duodenal adenocarcinoma was 66.5%. Conclusion Due to the soft pancreatic texture and small pancreatic duct, pancreatic resection for NADTs is associated with a high rate of POPF which contributes to reduced survival. Nevertheless, surgery is associated with favourable 5-year survival compared to pancreatic resection for pancreatic adenocarcinoma.

International audience; OBJECTIVE: The aim of this study was to compare oncological outcomes after minimally invasive distal pancreatectomy (MIDP) with open distal pancreatectomy (ODP) in patients with pancreatic ductal adenocarcinoma (PDAC). BACKGROUND: Cohort studies have suggested superior short-term outcomes of MIDP vs. ODP. Recent international surveys, however, revealed that surgeons have concerns about the oncological outcomes of MIDP for PDAC. METHODS: This is a pan-European propensity score matched study including patients who underwent MIDP (laparoscopic or robot-assisted) or ODP for PDAC between January 1, 2007 and July 1, 2015. MIDP patients were matched to ODP patients in a 1:1 ratio. Main outcomes were radical (R0) resection, lymph node retrieval, and survival. RESULTS: In total, 1212 patients were included from 34 centers in 11 countries. Of 356 (29%) MIDP patients, 340 could be matched. After matching, the MIDP conversion rate was 19% (n = 62). Median blood loss [200?mL (60-400) vs 300?mL (150-500), P = 0.001] and hospital stay [8 (6-12) vs 9 (7-14) days, P \textless 0.001] were lower after MIDP. Clavien-Dindo grade >=3 complications (18% vs 21%, P = 0.431) and 90-day mortality (2% vs 3%, P \textgreater 0.99) were comparable for MIDP and ODP, respectively. R0 resection rate was higher (67% vs 58%, P = 0.019), whereas Gerota's fascia resection (31% vs 60%, P \textless 0.001) and lymph node retrieval [14 (8-22) vs 22 (14-31), P \textless 0.001] were lower after MIDP. Median overall survival was 28 [95% confidence interval (CI), 22-34] versus 31 (95% CI, 26-36) months (P = 0.929). CONCLUSIONS: Comparable survival was seen after MIDP and ODP for PDAC, but the opposing differences in R0 resection rate, resection of Gerota's fascia, and lymph node retrieval strengthen the need for a randomized trial to confirm the oncological safety of MIDP.

Background: The laparoscopic approach in distal pancreatectomy is associated with higher rates of splenic preservation compared to open surgery. Although favorable postoperative short-term outcomes have been reported in open spleen-preserving distal pancreatectomy when compared to distal pancreatectomy with splenectomy, it is unclear whether this observation applies to the laparoscopic approach. The aim of this study is to compare laparoscopic spleen-preserving distal pancreatectomy (LSPDP) with laparoscopic distal pancreatectomy with splenectomy (LDPS). Study design: This is a UK wide, propensity score-matched study, including patients who underwent LSPDP or LDPS between 2006 and 2016. Short-term outcomes were compared between LSPDP and LDPS according to intention to treat. Additionally, risk factors for unplanned splenectomy were explored. Results: A total of 456 patients were included from eleven centers (229 LSPDP and 227 LDPS). We were able to match 173 LSPDP cases to 173 LDPS cases, according to intention to treat. No differences were seen in postoperative morbidity between the groups. The only identified risk factor for unplanned splenectomy was tumor size ≥ 30 mm. Conclusions: Preserving the spleen during laparoscopic distal pancreatectomy is not associated with a lower postoperative morbidity compared to sacrificing the spleen. Tumor size is a risk factor for unplanned splenectomy.

Pseudoaneurysms in the celiac territory are mostly managed conservatively. Endovascular thromboembolisation with or without stenting is currently the standard treatment with good outcome. We present a case of a patient with chronic pancreatitis who initially underwent endovascular treatment for presumed splenic artery pseudoaneurysm and subsequently required surgical intervention for complicated unnamed artery pseudoaneurysm. Radiological diagnosis was instrumental in guiding the ensuing surgical procedure and the patient made a good postoperative recovery.

Objective: The aim of the study was to define histopathologic characteristics that independently predict overall survival (OS) and disease-free survival (DFS), in patients who underwent resection of an ampullary adenocarcinoma with curative intent. Summary Background Data: A broad range of survival rates have been described for adenocarcinoma of the ampulla of Vater, presumably due to morphological heterogeneity which is a result of the different epitheliums ampullary adenocarcinoma can arise from (intestinal or pancreaticobiliary). Large series with homogenous patient selection are scarce. Methods: A retrospective multicenter cohort analysis of patients who underwent pancreatoduodenectomy for ampullary adenocarcinoma in 9 European tertiary referral centers between February 2006 and December 2017 was performed. Collected data included demographics, histopathologic details, survival, and recurrence. OS and DFS analyses were performed using Kaplan–Meier curves and Cox proportional hazard models. Results: Overall, 887 patients were included, with a mean age of 66 ± 10 years. The median OS was 64 months with 1-, 3-, 5-, and 10-year OS rates of 89%, 63%, 52%, and 37%, respectively. Histopathologic subtype, differentiation grade, lymphovascular invasion, perineural invasion, T-stage, N-stage, resection margin, and adjuvant chemotherapy were correlated with OS and DFS. N-stage (HR = 3.30 [2.09–5.21]), perineural invasion (HR = 1.50 [1.01–2.23]), and adjuvant chemotherapy (HR = 0.69 [0.48–0.97]) were independent predictors of OS in multivariable analysis, whereas DFS was only adversely predicted by N-stage (HR = 2.65 [1.65–4.27]). Conclusions: Independent predictors of OS in resected ampullary cancer were N-stage, perineural invasion, and adjuvant chemotherapy. N-stage was the only predictor of DFS. These findings improve predicting survival and recurrence after resection of ampullary adenocarcinoma.

To validate a preoperative predictive score of postoperative pancreatic fistula (POPF). Other risk factors for POPF were sought in an attempt to improve the score.POPF is the major contributor to morbidity after pancreaticoduodenectomy (PD). A preoperative score [using body mass index (BMI) and pancreatic duct width] to predict POPF was tested upon a multicenter patient cohort to assess its performance.Patients undergoing PD at 8 UK centers were identified. The association between the score and other pre-, intra-, and postoperative variables with POPF was assessed.A total of 630 patients underwent PD with 141 occurrences of POPF (22.4%). BMI, perirenal fat thickness, pancreatic duct width on computed tomography and at operation, bilirubin, pancreatojejunostomy technique, underlying pathology, T stage, N stage, R status, and gland firmness were all significantly associated with POPF. The score predicted POPF (P0.001) with a higher predictive score associated with increasing severity of POPF (P0.001). Stepwise multivariate analysis of pre-, intra-, and postoperative variables demonstrated that only the score was consistently associated with POPF. A table correlating the risk score to actual risk of POPF was created.The predictive score performed well and could not be improved. This provides opportunities for individualizing patient consent and selection, and treatment and research applications.

Background Acute pancreatitis (AP) continues to cause significant morbidity and mortality, especially when it leads to infected pancreatic necrosis (IPN). Modern treatment of IPN frequently involves prolonged courses of antibiotics in combination with minimally invasive therapies. This study aimed to update the existing evidence base by identifying the pathogens causing IPN and therefore aid future selection of empirical antibiotics. Methods Clinical data, including microbiology results, of consecutive patients with IPN undergoing minimally invasive necrosectomy at our institution between January 2009 and July 2016 were retrospectively reviewed. Results The results of 40 patients (22 males and 18 females, median age 60 years) with IPN were reviewed. The etiology of AP was gallstones, alcohol, dyslipidemia and unknown in 31, 2, 2 and 5 patients, respectively. The most frequently identified microbes in microbiology cultures were Enterococcus faecalis and faecium (22.5% and 20.0%) and Escherichia coli (20.0%). In 19 cases the cultures grew multiple organisms. The antibiotics with the least resistance amongst the microbiota were teicoplanin (5.0%), linezolid (5.6%), ertapenem (6.5%), and meropenem (7.4%). Conclusion The carbapenem antibiotics, ertapenem and meropenem provide good antimicrobial cover against the common, mainly enteral, microorganisms causing IPN. Culture and sensitivity results of acquired samples should be regularly reviewed to adjust prescribing and monitor for emergence of resistance.

Pancreaticoduodenectomy is often required in patients with duodenal adenoma and adenocarcinoma and these patients generally have soft pancreatic texture and small pancreatic ducts, the two most significant factors associated with post-operative pancreatic fistula (POPF). The aims of the study were to evaluate the rate of POPF and long-term outcomes for patients with duodenal adenoma and adenocarcinoma who underwent curative resection.This retrospective study (2004-2014) examined patients treated surgically with non-ampullary duodenal tumours (NADTs) in two hepatopancreaticobiliary units in Victoria, Australia, and Swansea, UK.There were 49 resections performed including 33 pancreaticoduodenectomies, five pancreas-preserving total duodenectomies and 11 segmental duodenal resections. Median length of follow-up was 23.5 months. Final histopathology revealed 18 duodenal adenomas and 31 adenocarcinomas. POPF rate for NADTs was 28.9% (of which 54.5% were grade C) compared to 14.5% for all other pathologies. Grade C POPF was associated with poorer survival outcomes (hazard ratio = 6.73; P = 0.005). The 5-year overall survival for patients with duodenal adenocarcinoma was 66.5%.Due to the soft pancreatic texture and small pancreatic duct, pancreatic resection for NADTs is associated with a high rate of POPF which contributes to reduced survival. Nevertheless, surgery is associated with favourable 5-year survival compared to pancreatic resection for pancreatic adenocarcinoma.

Kidins220 (Kinase D-Interacting Substrate, 220kDa), also known as ARMS (ankyrin repeat-rich membrane spanning) is a transmembrane scaffolding protein. Kidins220 acts as a platform for protein-protein interactions to coordinate cell plasticity, migration and neural growth receptor signalling. Present study aims to investigate the involvement of Kidins220 in the disease progression of pancreatic cancer. Pancreatic tumors (n=149) together with paired adjacent background tissues were collected at Peking University Cancer Hospital with written consent from the patients and also an ethical approval from the Peking University Cancer Hospital Research Ethics Committee. Kidins220 transcript levels were determined using real-time PCR. Relevance of Kidins220 transcript levels and pathologic/clinical features was analyzed. Knockdown of Kidins220 was carried out with a lentiviral Kidins220 shRNA. Immunohistochemical (IHC) staining of Kidins220 was performed on a pancreatic tissue microarray (TMA) (PA2081a, US Biomax, Inc., Rockville, MD, USA). A decreased expression of Kidins220 transcripts was observed in pancreatic cancer tissues in comparison with the paired background control (P=0.029). According to the TNM staging, early stage tumors (TNM 1&2) expressed higher levels of Kidins220 transcripts compared with its expression in more advanced tumors (TNM 3&4 stage, p=0.0034). In line with the finding from the Beijing pancreatic cancer cohort, a reduced expression of Kidins220 protein was seen in the pancreatic carcinomas of the TMA using IHC, p Citation Format: Shuo Cai, Ping-Hui Sun, Xiangyu Gao, Ke Ji, Xiuyun Tian, Chunyi Hao, Bilal Al-Sarireh, Paul Griffiths, Steven Hiscox, Jared Tonkington, Jun Cai, Wen G. Jiang, Lin Ye. Reduced kinase D-interacting substrate of 220kDa (Kidins220) in pancreatic cancer promotes EGFR/ERK signaling and disease progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 89.

OBJECTIVES Laparoscopic techniques have been slow to establish a role in pancreatic surgery. Worldwide, laparoscopic left pancreatectomy (LLP) is gaining in popularity; however, there remains little published data from the United Kingdom.We aimed to evaluate the results of LLP performed in a single UK pancreatic unit. METHODS Patients undergoing LLP for lesions in the body and tail of the pancreas between April 2009 and April 2015 were identified. Patient records were reviewed retrospectively. RESULTS Laparoscopic left pancreatectomy was performed on 46 patients, median age, 62 years (range, 19-84). The spleen was preserved in 27 patients (93% of planned), and 6 (13%) operations were converted to open. The overall morbidity rate was 39%; 28 patients had no complications. Significant complications were seen in 7 (15%) patients; this included 3 pancreatic fistula (6.5%) and 1 mortality (2%). Median length of stay was 6 days (range, 3-28). Histology revealed 15 neuroendocrine tumors, 8 adenocarcinomas, 4 mucinous cystadenomas, 1 intraductal papillary mucinous neoplasm, 2 metastases, and 16 other benign pathologies. CONCLUSIONS Laparoscopic pancreatic surgery has a low risk of significant complications. Our results offer encouragement to identify LLP as the gold standard approach for premalignant lesions. Further work should clarify the outcomes for malignant lesions.

Familial adenomatous polyposis affects around 2-10 per 100,000 population. Untreated, it inevitably leads to colon cancer. Prophylactic panproctocolectomy has led to improved survival. The resulting extension to follow-up has revealed that 70-100% of patients with familial adenomatous polyposis go on to develop duodenal polyposis and the lifetime risk of duodenal carcinoma in this group is up to 10%. Treatment for those not locally resectable requires pancreaticoduodenectomy. In recent years, pancreas-preserving total duodenectomy has emerged as a safe alternative to pancreaticoduodenectomy. Endoscopy has previously been safely performed in patients following pancreas-preserving total duodenectomy.We report successful endoscopic ultrasound (EUS) assessment and trans-neoduodenal EUS-guided fine needle aspiration biopsy (EUS-FNA) of the pancreas and adjacent tissue in a 45-year-old man with familial adenomatous polyposis who has previously undergone pancreas-preserving total duodenectomy. EUS confirmed the mass was most likely to represent a metastasis in a local lymph node. EUS-FNA confirmed invasive malignancy. A Kausch-Whipple pancreaticoduodenectomy was performed successfully and post-operative recovery has been excellent.The authors consider this to be the first report of successful EUS and EUS-FNA performed through the neoduodenum fashioned during pancreas-preserving total duodenectomy.