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Background Effective chemotherapy (CTx) protocols as induction treatment provide increasing opportunities for surgical resection of locally advanced pancreatic cancer (LAPC). Although improved survival after resection of LAPC with CTx has been reported for selected patients, reliable recommendations on the indication for conversion surgery after induction treatment are currently lacking. We investigated the factors predictive of prognosis in resected LAPC after FOLFIRINOX. Methods Consecutive patients with LAPC undergoing curative resection after FOLFIRINOX between 2011 and 2018 were identified from a prospectively maintained database. Relevant clinical parameters and CT findings were examined. A scoring system was developed based on the ratio of hazard ratios for overall survival of all significant predictors. Results A total of 62 patients with LAPC who underwent oncologic resection after FOLFIRINOX were analyzed. Tumor shrinkage, tumor density, and postchemotherapy CA19-9 serum levels were independently associated with overall survival (multivariate analysis: HR = 0.31, 0.17, and 0.18, respectively). One, two, and two points were allocated to these three factors in the proposed scoring system, respectively. The median overall survival of patients with a score from 0 to 2 was significantly shorter than that of patients with a score from 3 to 5 (22.1 months vs. 53.2 months, P < 0.001). Conclusions Tumor density is a novel predictive marker for the prognosis of patients with resected LAPC after FOLFIRINOX. A simple scoring model incorporating tumor density, the tumor shrinkage rate, and CA 19-9 levels identifies patients with a low score, who may be candidates for additional treatment.

Background The treatment of complicated intra-abdominal infections remains a challenge. Both optimal medical and surgical therapy (i.e., source control) are needed to achieve low mortality and morbidity. The objective of this systematic review and meta-analysis is to determine the impact of carbapenem antibiotic therapy compared to other antibiotics in complicated intra-abdominal infections (secondary peritonitis) with an emphasis on mortality and postoperative complications. Methods A systematic literature search from PubMed/Medline and Web of Science databases was carried out. The last search was conducted in August 2022. PRISMA guidelines were followed. Pre-defined outcomes were mortality, treatment success, treatment failure, and adverse events. Results Ten randomized controlled trials, published from 1983 to 2013 with a total of 2377 patients (1255 patients in the carbapenem antibiotics group and 1122 in the control group), were identified. A meta-analysis comparing patients undergoing carbapenem antibiotic therapy and patients receiving other antibiotics was performed. No significant difference regarding mortality (OR 1.19, 95% CI [0.79; 1.82], p = 0.40), treatment success (OR 1.17, 95% CI [0.72; 1.91], p = 0.53), and treatment failure (OR 0.84, 95% CI [0.48; 1.45], p = 0.52) was observed. Carbapenem therapy was associated with fewer adverse events compared to therapy with other antibiotics (OR 0.79, 95% CI [0.65; 0.97], p = 0.022). Conclusion There is currently no evidence that carbapenem antibiotics are superior in terms of mortality, and success or failure for the treatment of complicated intra-abdominal infections (secondary peritonitis). The rate of adverse events is lower under carbapenem therapy compared to control antibiotics. Trial Registration PROSPERO 2018 CRD42018108854.

Background Gastric cancer is one of the most frequent malignancies worldwide. Angiogenic growth factors play a crucial role in mediating the crosstalk between cancer cells and the surrounding microenvironment. In this exploratory study, we investigate the impact of angiogenic proteins within the tumor cell or stroma compartment on survival of patients with gastric cancer. Materials and methods In 29 patients, tumor and stromal compartments were separated using laser capture microdissection. Angiogenic protein expression was measured using a bead-based immunoassay and correlated with tumor stage and overall survival. Results Overall survival was significantly shorter in patients with a high stroma concentration of vascular endothelial growth factor (VEGF)-A (23.5 (±17.6) versus 33.6 (±21.0) mo; P = 0.009) and stem cell factor (22.2 (±18.5) versus 33.6 (±21.8) mo; P = 0.01) compared with patients with a low stroma concentration. High stromal VEGF-D showed a trend toward worse survival (26.8 (±22.0) versus 37.2 (±19.0) mo; P = 0.09). We did not observe any significant correlation between tumor-specific expression of angiogenic cytokines and survival. Conclusions This translational study highlights the difference in clinical impact between tumor and stromal expression of angiogenic proteins. Compartment-specific concentrations of VEGF-A and stem cell factor affect the clinical prognosis and help to identify the best therapy for patients with gastric cancer.

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

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.

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.