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Background Malnutrition is associated with poor survival in pancreatic cancer patients. Nutritional scores show great heterogeneity diagnosing malnutrition. The aim of this study was to find the score best suitable to identify patients with malnutrition related to worse survival after surgery for pancreatic ductal adenocarcinoma (PDAC). This study represents a follow‐up study to the prospective NURIMAS Pancreas trial that evaluated short term impact of nutritional score results after surgery. Methods Risk of malnutrition was evaluated preoperatively using 12 nutritional assessment scores. Patients were followed‐up prospectively for at least 3 years. Patients at risk for malnutrition were compared with those not at risk according to each score using Kaplan–Meier survival statistics. Results A total of 116 patients receiving a PDAC resection in curative intent were included. Malnutrition according to the Subjective Global Assessment score (SGA), the Short Nutritional Assessment Questionnaire (SNAQ), and the INSYST2 score was associated with worse overall survival (SGA: at‐risk: 392 days; not at‐risk: 942 days; P = 0.001; SNAQ: at‐risk: 508 days; not at‐risk: 971 days; P = 0.027; INSYST2: at‐risk: 538 days; not at risk: 1068; P = 0.049). In the multivariate analysis, SGA (hazard ratio of death 2.16, 95% confidence interval 1.34–3.47, P = 0.002) was associated with worse overall survival. Conclusions Malnutrition as defined by the Subjective Global Assessment is independently associated with worse survival in resected PDAC patients. The SGA should be used to stratify PDAC patients in clinical studies. Severely malnourished patients according to the SGA profit from intensified nutritional therapy should be evaluated in a randomized controlled trial.

Objective Advances in multimodality treatment paralleled increasing numbers of complex pancreatic procedures with major vascular resections. The aim of this meta-analysis was to evaluate the current outcomes of arterial resection (AR) in pancreatic surgery. Methods A systematic literature search was carried out from January 2011 until January 2020. MOOSE guidelines were followed. Predefined outcomes were morbidity, pancreatic fistula, postoperative bleeding and delayed gastric emptying, reoperation rate, mortality, hospital stay, R0 resection rate, and lymph node positivity. Duration of surgery, blood loss, and survival were also analyzed. Results Eight hundred and forty-one AR patients were identified in a cohort of 7111 patients. Morbidity and mortality rates in these patients were 66.8% and 5.3%, respectively. Seven studies (579 AR patients) were included in the meta-analysis. Overall morbidity (48% vs 39%, p = 0.1) and mortality (3.2% vs 1.5%, p = 0.27) were not significantly different in the groups with or without AR. R0 was less frequent in the AR group, both in patients without (69% vs 89%, p p p = 0.037). Conclusions Arterial resections increase the complexity of pancreatic surgery, as demonstrated by relevant morbidity and mortality rates. Careful patient selection and multidisciplinary planning remain important.

The optimal surgical strategy for pancreatic neuroendocrine tumors (PNETs) is unknown. However, current guidelines recommend a watch-and-wait strategy for small nonfunctional PNETs (NF-PNETs). The aim of this study is to investigate the risk stratification and prognostic significance of lymph node metastasis (LNM) of PNETs to guide decision-making for lymphadenectomy. The MEDLINE and Web of Science databases were systematically searched for studies reporting either risk factors of LNM in resected PNETs or survival of patients with LNM. The weighted average incidence of LNM was calculated according to tumor characteristics. Random-effects metaanalyses were performed, and pooled hazard ratios (HR) and their 95% confidence intervals (CI) were calculated to determine the impact of LNM on overall survival (OS). In subgroup analyses, NF-PNETs were assessed. From a total of 5883 articles, 98 retrospective studies with 13,374 patients undergoing resection for PNET were included. In all PNETs, the weighted median rates of LNM were 11.5% for small (≤ 2 cm) PNETs and 15.8% for G1 PNETs. In NF-PNETs, the rates were 11.2% for small PNETs and 10.3% for G1 PNETs. LNM of all PNETs (HR 3.87, 95% CI 3.00–4.99, P

Pancreatic ductal adenocarcinoma (PDAC) is an oligosymptomatic disease, that is usually diagnosed in an advanced tumor stage. Traditionally, only the small subset of patients with tumors that showed no signs of vascular infiltration and distant metastases proceeded to surgery-still the only curative therapeutic modality to date. The remaining majority of patients received palliative chemotherapy or chemoradiation, usually with gemcitabine monotherapy. While gemcitabine monotherapy results in improved survival compared to best supportive care, most patients still succumb to the disease under therapy in a relatively short amount of time. Over the last years and decades, paradigms have shifted in PDAC treatment and potent multidrug chemotherapy protocols, including gemcitabine plus nab-paclitaxel and FOLFIRINOX, result in sufficient downstaging of advanced tumors in many patients. In this context, more and more patients are eligible for exploration and often resection. In this review we discuss the current state of the art in the clinical management and surgical treatment of patients with locally advanced pancreatic cancer, including classifications of locally advanced and borderline disease and surgical strategies for extended resections. An emphasis is put on arterial and venous resections and their outcome. In the end, we discuss current gaps in the literature and propose directions future research endeavors should focus on.

Initial recurrence mapping of resected pancreatic ductal adenocarcinoma (PDAC) could help in stratifying patient subpopulations for optimal postoperative follow-up. The aim of this systematic review and meta-analysis was to investigate the initial recurrence patterns of PDAC and to correlate them with clinicopathological factors.MEDLINE and Web of Science databases were searched systematically for studies reporting first recurrence patterns after PDAC resection. Data were extracted from the studies selected for inclusion. Pooled odds ratios (ORs) and 95 per cent confidence intervals were calculated to determine the clinicopathological factors related to the recurrence sites. The weighted average of median overall survival was calculated.Eighty-nine studies with 17 313 patients undergoing PDAC resection were included. The weighted median rates of initial recurrence were 20·8 per cent for locoregional sites, 26·5 per cent for liver, 11·4 per cent for lung and 13·5 per cent for peritoneal dissemination. The weighted median overall survival times were 19·8 months for locoregional recurrence, 15·0 months for liver recurrence, 30·4 months for lung recurrence and 14·1 months for peritoneal dissemination. Meta-analysis revealed that R1 (direct) resection (OR 2·21, 95 per cent c.i. 1·12 to 4·35), perineural invasion (OR 5·19, 2·79 to 9·64) and positive peritoneal lavage cytology (OR 5·29, 3·03 to 9·25) were significantly associated with peritoneal dissemination as initial recurrence site. Low grade of tumour differentiation was significantly associated with liver recurrence (OR 4·15, 1·71 to 10·07).Risk factors for recurrence patterns after surgery could be considered for specific surveillance and treatments for patients with pancreatic cancer.El mapeo del patrón de recidiva inicial tras la resección de un adenocarcinoma ductal pancreático (pancreatic ductal adenocarcinoma, PDAC) podría ayudar a estratificar subpoblaciones de pacientes para un seguimiento postoperatorio óptimo. El objetivo de esta revisión sistemática con metaanálisis fue investigar los patrones de recidiva inicial de PDAC y correlacionarlos con factores clínico-patológicos. MÉTODOS: Se realizaron búsquedas sistemáticas en las bases de datos MEDLINE y Web of Science para seleccionar estudios que presentaran información sobre los patrones de recidiva inicial después de la resección del PDAC. Se extrajeron los datos de los estudios seleccionados para su inclusión en el metaanálisis. Se calcularon las razones de oportunidades agrupadas (pooled odds ratio, OR) y los i.c. del 95% para definir los factores clínico-patológicos relacionados con las localizaciones de la recidiva. Se estimó el promedio ponderado de la mediana de la supervivencia global.Se incluyeron 89 estudios con 17.313 pacientes a los que se realizó una resección por PDAC. Las tasas medias ponderadas de las localizaciones de la recidiva inicial fueron del 20,8% para la locorregional, 26,5% para las hepáticas, 11,4% para el pulmón y 13,5% para la diseminación peritoneal. La mediana ponderada de supervivencia global fue de 19,8 meses (locorregional), 15,0 meses (hígado), 30,4 meses (pulmón) y 14,1 meses (diseminación peritoneal). El metaanálisis demostró que la resección R1 (inicial) (OR 2,21, i.c. del 95% 1,12-4,35), la invasión perineural (OR 5,19; i.c. del 95% 2,79-9,64) y la positividad de la citología del lavado peritoneal (OR 5,29; i.c. del 95% 3,03-9,25) se asociaron significativamente con la diseminación peritoneal como localización de recidiva inicial. El bajo grado de diferenciación tumoral se asoció significativamente con la recidiva hepática (OR 4,15; i.c. del 95%: 1,71-10,07). CONCLUSIÓN: Se podrían tener en cuenta estos factores de riesgo de los patrones de recidiva tras la cirugía para realizar un seguimiento y tratamiento específicos en pacientes con cáncer de páncreas.

Background Effective chemotherapy protocols are currently changing the treatment options for metastasized pancreatic cancer. Survival benefits after synchronous metastasectomy have been reported for selected patients. We set out to assess predictive factors of resectability for synchronous metastases after FOLFIRINOX. Methods Consecutive patients with metastatic pancreatic cancer undergoing surgery after FOLFIRINOX between 2011 and 2017 were identified from a prospectively collected database. Surgery following chemotherapy was indicated in patients with no more than six metastatic lesions, no progression detected on CT, and technically resectable disease. Patients who received synchronous metastasectomy were compared with patients who received explorative laparotomy or palliative surgery in terms of predictors of resectability and overall survival. In patients undergoing resection, prognostic factors were examined. Results Of 101 patients scheduled for surgery after FOLFIRINOX, synchronous metastasectomy was performed in 43 cases (43%) and non-resection surgery in 58 cases (57%). The shrinkage rate of the primary tumor on CT (P = 0.04) and the postchemotherapy serum CA19-9 concentration (P = 0.02) were associated with resectability. The median overall survival of the patients undergoing metastasectomy was longer than that of the patients without resection (21.9 months vs 16.4 months, P = 0.006). Postchemotherapy serum CA19-9 value (P = 0.04) and lymph node ratio (P = 0.01) were prognostic factors in the patients undergoing metastasectomy. Conclusions In selected patients who satisfied our surgical criteria, shrinkage rate of primary tumor and postchemotherapy serum CA19-9 level, which predict resectability of metastasized pancreatic cancer, should be considered in decision making to avoid unnecessary surgery.

The benefit of preoperative biliary stenting in the treatment of pancreatic ductal adenocarcinoma is controversially debated. Data from recent meta-analyses favor primary surgery for the majority of resectable pancreatic cancers. Regardless of this evidence, preoperative biliary stenting via endoscopy (EBS) is commonly performed, often before involvement of a surgeon. The goal of this study was to elucidate the association of bile duct stenting, microbiological dislocation of gut flora to the biliary compartment, and major postoperative complications. Patient data was derived from a prospectively maintained database including all pancreatic resections between January 2006 and December 2014. Patients receiving pancreaticoduodenectomy for malignant disease in the head of the pancreas with prior EBS were included. Microbiological data were obtained through conventional culture from intraoperative bile duct swabs. Two hundred ninety-eight patients were enrolled in this study. Severe postoperative complications were associated with stent colonization: Postoperative pancreatic fistula type C occurred more frequently in E. coli–colonized patients (sample estimated odds ratio (OR) = 4.07), and the rate of lymphatic fistula was elevated in Enterococcus-colonized patients (OR = 3.25). Longer stenting duration (> 16 days) was associated with the prevalence of these bacteria. Major surgical complications following pancreaticoduodenectomy, including severe pancreatic fistula, are associated with bacterobilia after EBS. The indication for bile duct stenting should be evaluated in a multidisciplinary setting.

Background The optimal nutritional treatment after pancreatoduodenectomy is still unclear. The aim of this meta-analysis was to investigate the impact of routine enteral nutrition following pancreatoduodenectomy on postoperative outcomes. Methods RCTs comparing enteral nutrition (regular oral intake with routine tube feeding) with non-enteral nutrition (regular oral intake with or without parenteral nutrition) after pancreatoduodenectomy were sought systematically in the MEDLINE, Cochrane Library and Web of Science databases. Postoperative data were extracted. Random-effects meta-analyses were performed to compare postoperative outcomes in the two arms, and pooled odds ratios (ORs) or mean differences (MDs) were calculated with 95 per cent confidence intervals. In subgroup analyses, the routes of nutrition were assessed. Percutaneous tube feeding and nasojejunal tube feeding were each compared with parenteral nutrition. Results Eight RCTs with a total of 955 patients were included. Enteral nutrition was associated with a lower incidence of infectious complications (OR 0·66, 95 per cent c.i. 0·43 to 0·99; P = 0·046) and a shorter length of hospital stay (MD –2·89 (95 per cent c.i. –4·99 to –0·80) days; P < 0·001) than non-enteral nutrition. Percutaneous tube feeding had a lower incidence of infectious complications (OR 0·47, 0·25 to 0·87; P = 0·017) and a shorter hospital stay (MD –1·56 (–2·13 to –0·98) days; P < 0·001) than parenteral nutrition (3 RCTs), whereas nasojejunal tube feeding was not associated with better postoperative outcomes (2 RCTs). Conclusion As a supplement to regular oral diet, routine enteral nutrition, especially via a percutaneous enteral tube, may improve postoperative outcomes after pancreatoduodenectomy.

Objective Malnutrition is associated with poor survival in pancreatic cancer patients. Nutritional scores show great heterogeneity diagnosing malnutrition. The aim of this study was to find the score best suitable to identify patients with malnutrition related to worse survival after surgery for PDAC. Methods Risk of malnutrition was evaluated preoperatively using twelve nutritional assessment scores. Patients were followed-up prospectively for at least 3 years. Patients at risk for malnutrition were compared to those not at risk according to each score using Kaplan Meier survival statistics. Results A total of 116 Patients receiving a PDAC resection in curative intent were included. Malnutrition according to the Subjective Global Assessment score (SGA), the Short Nutritional Assessment Questionnaire (SNAQ) and the INSYST2 score was associated with worse overall survival (SGA: at-risk: 392 days; not at-risk: 942 days; p = 0.001; SNAQ: at-risk: 508 days; not at-risk: 971 days; p = 0.027; INSYST2: at-risk: 538 days; not at risk: 1068; p = 0.049). In the multivariate analysis SGA (HR of death 2.22, 95% CI 1.37-3.6, p = 0.002) was associated with worse overall survival. Conclusion Malnutrition as defined by the Subjective Global Assessment is independently associated with worse survival in resected PDAC patients. The SGA should be used to stratify PDAC patients in clinical studies. If severely malnourished patients according to the SGA profit from intensified nutritional therapy should be evaluated in a randomized controlled trial.

Background Acute pancreatitis (AP) is defined as an acute inflammatory attack of the pancreas of sudden onset. Around 25% of patients have either moderately severe or severe disease with a mortality rate of 15–20%. Purpose The aim of this article was to summarize the advances being made in the understanding of this disease and the important role of surgery. Results and conclusions An accurate diagnosis should be made a soon as possible, initiating resuscitation with large volume intravenous fluids and oxygen by mask. Predicted severe disease will require intensive monitoring. Most deaths within the first week are due to multi-organ failure; thus, these patients will require intensive therapy unit management. During the second phase of the disease, death is due to local complications arising from the pancreatic inflammation, requiring accurate identification to determine the correct form of treatment. Acute peripancreatic fluid collections arise 4 weeks and largely resolve on conservative management. Necrotizing pancreatitis causing acute necrotic collections and later walled-off necrosis will require treatment if symptomatic or infected. Initial endoscopic transgastric or percutaneous drainage will resolve less serious collections but necrosectomy using minimally invasive approaches will be needed for more serious collections. To prevent recurrent attacks of AP, causative factors need to be removed where possible such as cholecystectomy and cessation of alcohol. Future progress requires improved management of multi-organ failure and more effective minimally invasive techniques for the removal of necrosis.

OBJECTIVE To build a prognostic score for patients with primary chemotherapy undergoing surgery for pancreatic cancer based on pathological parameters and preoperative Carbohydrate antigen 19-9 (CA19-9) levels. BACKGROUND Prognostic stratification after primary chemotherapy for pancreatic cancer is challenging and prediction models, such as the AJCC staging system, lack validation in the setting of preoperative chemotherapy. METHODS Patients with primary chemotherapy resected at the Massachusetts General Hospital between 2007 and 2017 were analyzed. Tumor characteristics independently associated with overall survival were identified and weighted by Cox-proportional regression. The pancreatic neoadjuvant Massachusetts-score (PANAMA-score) was computed from these variables and its performance assessed by Harrel concordance index and area under the receiving characteristics curves analysis. Comparisons were made with the AJCC staging system and external validation was performed in an independent cohort with primary chemotherapy from Heidelberg, Germany. RESULTS A total of 216 patients constituted the training cohort. The multivariate analysis demonstrated tumor size, number of positive lymph-nodes, R-status, and high CA19-9 to be independently associated with overall survival. Kaplan-Meier analysis according to low, intermediate, and high PANAMA-score showed good discriminatory power of the new metrics (P < 0.001). The median overall survival for the three risk-groups was 45, 27, and 12 months, respectively. External validation in 258 patients confirmed the prognostic ability of the score and demonstrated better accuracy compared with the AJCC staging system. CONCLUSION The proposed PANAMA-score, based on independent predictors of postresection survival, including pathologic variables and CA19-9, not only provides better discrimination compared to the AJCC staging system, but also identifies patients at high-risk for early death.

The number of lymph nodes to be resected in surgery for non-pancreatic periampullary cancer remains unclear.The Surveillance, Epidemiology, and End Results (SEER) database was used to gather information from a large retrospective cohort. To define a novel, reasonable cut-off associated with survival, we stratified patients into subgroups depending on the number of resected lymph nodes.1481 nodal-negative patients resected for periampullary cancer (excluding pancreatic ductal adenocarcinoma) were included. The median number of resected lymph nodes was ten. Median overall survival in the subgroup with less than 10 removed lymph nodes was 40 months, while median survival for patients with ≥10 lymph nodes was 97 months (p 0.001). A significant survival benefit was seen if ≥ 16 lymph nodes were harvested (median survival, 117 months), while no further benefit was observed if more than 21 nodes were removed (median survival,120 months).Sixteen or more resected lymph nodes are associated with improved survival in node-negative periampullary carcinoma. We propose to aim at harvesting and analyzing at least 16 lymph nodes.

Site-specific outcomes of resection for periampullary cancer have not been analyzed on a large, registry-based scale. We assessed data on periampullary cancers from the SEER database. Site- and stage-specific outcomes were analyzed. Resection was compared to no resection. Resection was the main therapy in stages 1 and 2 (resection vs. no resection, 8644 vs. 7208 patients), was less frequent in stage 3 (1248 vs. 2783 patients) and was rarely—but still—used in stage 4 disease (541 vs. 11,212 patients). Pancreatic head (75.7%), 11.4% distal bile duct, 7.7% ampullary, and 5.3% duodenal cancers. Cancer subtype-independent median survival was 22.0 (resection) vs. 7.0 months (no resection) in stages 1 and 2, 21.0 vs. 8.0 months in stage 3, and 10.0 vs. 3.0 months in stage 4. Subtype-dependent median survival (resection vs. no resection) was 18.0 vs. 5.0 months in pancreatic head, 19.0 vs 4.0 months in distal bile duct, 41.0 vs 7.0 months in ampullary, and 38.0 vs 4.0 months in duodenal adenocarcinoma. On multivariable analysis, patient comorbidities, marital and insurance status, and income all influenced the decision to undergo resection. Surgery is still underutilized in the treatment of periampullary cancers. Patients with cancers originating from the duodenum or the ampulla of Vater benefit most from resectional surgery.

Background Estimation of the risk of malignancy in intraductal papillary mucinous neoplasia (IPMN) of the pancreas is a clinical challenge. Several routinely used clinical factors form the basis of the current consensus guidelines. This study aimed to determine the predictive values of the most commonly assessed risk factors. Methods A meta-analysis of individual risk factors of malignancy in IPMN was performed. Contingency tables were derived from these data, and sensitivity, specificity, negative and positive predictive values, and diagnostic odds ratios (DOR) were determined. Hierarchical summary receiver operating characteristic (HSROC) curves for each factor were calculated and the respective area under the curve (AUC) was assessed. Results A total of 3443 studies were screened initially. Analysis of recent literature revealed 60 studies with 13 relevant risk factors including clinical, serological and radiological parameters. The largest area under the HSROC curve was found for weight loss (0·84) and jaundice/raised bilirubin level (0·80), followed by increased carcinoembryonic antigen (CEA) (0·79) or carbohydrate antigen (CA) 19-9 (0·78) levels. The most sensitive factors were patient age (71 per cent) and mural nodules (65 per cent), and jaundice/raised bilirubin level (97 per cent) and increased CEA level (95 per cent) were most specific. None of the analysed factors reached a positive or negative level of prediction beyond 90 per cent. Conclusion None of the established criteria safely distinguishes malignant from non-malignant lesions.

The risk of malignancy in branch duct intraductal papillary mucinous neoplasia of the pancreas (BD-IPMN) is controversially debated. An increasing number of studies report on outcomes using the Sendai or Fukuoka consensus criteria for treatment decision-making. The objective of this work was to evaluate the diagnostic accuracy of the Sendai and Fukuoka criteria.We systematically reviewed studies on Sendai or Fukuoka criteria-guided management of BD-IPMN. Pooled sensitivity, specificity and diagnostic odds ratios as compound measures of diagnostic accuracy were calculated from studies matching the inclusion criteria. The meta-analysis was performed using a random effects model.Fifteen studies with a total of 2710 patients were included. Twelve of these used the Sendai criteria. In these studies, 23% of Sendai-negative patients had a high grade dysplastic lesion or an invasive carcinoma in final histology. Pooled sensitivity was 56%, specificity was 74% and the diagnostic odds ratio for malignancy in Sendai-positive lesions was 7.45. When the results of follow-up examinations were included, diagnostic accuracy improved significantly (14.66, p 0.001). Three studies were identified that used the Fukuoka criteria for decision making. Of 200 patients with Fukuoka-negative lesions who underwent surgery, 22 had a malignant lesion in final histology (11%). Pooled sensitivity was 83%, specificity was 53% and the diagnostic odds ratio was 8.76.The Fukuoka criteria have considerably improved sensitivity but still lack adequate specificity. For further reduction of a potential surgical overtreatment of BD-IPMN, the development of criteria with an increased specificity is required.

Background & Aims Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas can progress to cancer. Biomarkers have been identified that were reported to increase the accuracy of identification of malignant lesions; we performed a systematic review of the accuracy of these markers. Methods We performed a systematic review of published studies on biomarkers of malignant IPMNs by searching MEDLINE and Web of Science databases from January 2005 through December 2017. Our methods were developed based on the Meta-analysis Of Observational Studies in Epidemiology guidelines. Pooled sensitivity, specificity, receiver operating characteristic curves, and their respective areas under the curve (AUC) were calculated from groups of markers (cell-, protein-, or DNA-based) measured in samples collected before and after surgery. A hypothetical test model was developed to determine how to meaningfully amend the revised Fukuoka guidelines, focusing on increasing test specificity for patients with IPMNs that have worrisome features. Results We collected data from 193 published studies, comprising 12,297 patients, that analyzed 7 preoperative and 21 postoperative markers of IPMNs. The 3 biomarkers that identified malignant IPMNs with the largest AUC values were pancreatic juice cytology (AUC, 0.84; sensitivity, 0.54; specificity, 0.91), serum protein carbohydrate antigen 19-9 (AUC, 0.81; sensitivity, 0.45; specificity, 0.90), and cyst fluid cytology (AUC, 0.82; sensitivity, 0.57; specificity, 0.84). A combination of cytologic and immunohistochemical analysis of MUC1 and MUC2 in pancreatic juice samples identified malignant IPMNs with the largest AUC and sensitivity values (AUC, 0.85; sensitivity, 0.85; specificity, 0.65). In a test model, inclusion of cytologic analysis of pancreatic juice in the guideline algorithm significantly increased the specificity of detection of malignant IPMNs. Conclusions In a systematic review, we found cytologic analysis of pancreatic juice to have the greatest effect in increasing the specificity of detection of malignant IPMNs. We propose addition of this test to the Fukuoka guidelines for assessment of patients with IPMNs with worrisome features.