Anatomy of the neural fibers at the superior mesenteric artery-a cadaver study

PURPOSE Most surgeons perform right-sided semicircular clearance of the superior mesenteric artery (SMA) nerve plexus for pancreatic head carcinoma, presuming a linear course of the SMA nerve fibers. The hypothesis was that the SMA nerve plexus fibers follow a non-linear course, and the goal of the present study was to assess the neural fibers distribution along the SMA. METHODS The course of neural fibers along the retropancreatic and suprapancreatic SMA was assessed in 7 cadavers. RESULTS In the retropancreatic course of the vessel, the main nerve cords branch and form a large number of finer nerve branches performing an anti-clockwise rotation of slightly less than 90° around the SMA. Finer nerve branches are located rather close to the vessel, while the main nerve cords are localized in the loose connective tissue of the peripheral parts of the vascular sheath. Nerve fibers around the suprapancreatic SMA run as two main nerve cords framing the artery on the right lateral-ventral and the left lateral to lateral-dorsal side. CONCLUSION The rotation of the nerve fiber around the SMA indicates that a more radical resection of at least 180° of neural tissue around the SMA might be required to achieve tumor clearance in pancreatic cancer with perineural invasion at the uncinate margin

Multivisceral resection of pancreatic neuroendocrine tumours: a report of two cases

Pancreatic neuroendocrine tumours (pNETs) are rare and surgical resection offers the only possibility of cure for localised disease. The role of surgery in the setting of locally advanced and metastatic disease is more controversial. Emerging data suggests that synchronous surgical resection of pancreas and liver may be associated with increased survival. We report two cases of synchronous, one stage multivisceral resections for pNET and associated reconstruction. We highlight the technical issues involved in such extensive resections and demonstrate that one stage multivisceral operations can be achieved safely

Extended lymph node resection versus standard resection for pancreatic and periampullary adenocarcinoma

BACKGROUND Pancreatic and periampullary adenocarcinomas account for some of the most aggressive malignancies, and the leading causes of cancer-related mortalities. Partial pancreaticoduodenectomy (PD) with negative resection margins is the only potentially curative therapy. The high prevalence of lymph node metastases has led to the hypothesis that wider excision with the removal of more lymphatic tissue could result in an improvement of survival, and higher rates of negative resection margins. OBJECTIVES To compare overall survival following standard (SLA) versus extended lymph lymphadenectomy (ELA) for pancreatic head and periampullary adenocarcinoma. We also compared secondary outcomes, such as morbidity, mortality, and tumour involvement of the resection margins between the two procedures. SEARCH METHODS We searched CENTRAL, MEDLINE, PubMed, and Embase from 1973 to September 2020; we applied no language restrictions. SELECTION CRITERIA Randomised controlled trials (RCT) comparing PD with SLA versus PD with ELA, including participants with pancreatic head and periampullary adenocarcinoma. DATA COLLECTION AND ANALYSIS Two review authors independently screened references and extracted data from study reports. We calculated pooled risk ratios (RR) for most binary outcomes except for postoperative mortality, for which we estimated a Peto odds ratio (Peto OR), and mean differences (MD) for continuous outcomes. We used a fixed-effect model in the absence of substantial heterogeneity (I² 25%). Two review authors independently assessed risk of bias, and we used GRADE to assess the quality of the evidence for important outcomes. MAIN RESULTS We included seven studies with 843 participants (421 ELA and 422 SLA). All seven studies included Kaplan-Meier curves for overall survival. There was little or no difference in survival between groups (log hazard ratio (log HR) 0.12, 95% confidence interval (CI) -3.06 to 3.31; P = 0.94; seven studies, 843 participants; very low-quality evidence). There was little or no difference in postoperative mortality between the groups (Peto odds ratio (OR) 1.20, 95% CI 0.51 to 2.80; seven studies, 843 participants; low-quality evidence). Operating time was probably longer for ELA (mean difference (MD) 50.13 minutes, 95% CI 19.19 to 81.06 minutes; five studies, 670 participants; moderate-quality evidence). There was substantial heterogeneity between the studies (I² = 88%; P < 0.00001). There may have been more blood loss during ELA (MD 137.43 mL, 95% CI 11.55 to 263.30 mL; two studies, 463 participants; very low-quality evidence). There was substantial heterogeneity between the studies (I² = 81%, P = 0.02). There may have been more lymph nodes retrieved during ELA (MD 11.09 nodes, 95% CI 7.16 to 15.02; five studies, 670 participants; moderate-quality evidence). There was substantial heterogeneity between the studies (I² = 81%, P < 0.00001). There was little or no difference in the incidence of positive resection margins between groups (RR 0.81, 95% CI 0.58 to 1.13; six studies, 783 participants; very low-quality evidence). AUTHORS' CONCLUSIONS There is no evidence of an impact on survival with extended versus standard lymph node resection. However, the operating time may have been longer and blood loss greater in the extended resection group. In conclusion, current evidence neither supports nor refutes the effect of extended lymph lymphadenectomy in people with adenocarcinoma of the head of the pancreas

Il monastero benedettino di S. Giorgio in Braida a Verona: nuove prospettive di ricerca sulla rifabbrica romanica (sec. XII)

L’attuale aspetto rinascimentale della chiesa di San Giorgio in Braida è frutto di una serie di interventi promossi dai canonici veneziani di San Giorgio in Alga a partire dalla fine del XV secolo. Il monastero benedettino, tuttavia, fu fondato nella metà dell’XI secolo e completamente ricostruito fra il terzo e il quarto decennio del secolo successivo per volere del vescovo Bernardo. L’articolo ripercorre le vicende storiche dell’istituzione in età medievale e rende nota l’esistenza di alcune parti della compagine romanica tuttora inedite, che permettono d’inserire il cantiere di San Giorgio in Braida nel contesto delle coeve manifestazioni architettoniche veronesi

Biomarker panel predicts survival after resection in pancreatic ductal adenocarcinoma: a multi-institutional cohort study.

Background: Up to 60% of patients who undergo curative-intent pancreatic ductal adenocarcinoma (PDAC) resection experience disease recurrence within six months. We recently published a systematic review of prognostic immunohistochemical biomarkers in PDAC and shortlisted a panel of those reported with the highest level of evidence, including p53, p16, Ca-125, S100A4, FOXC1, EGFR, mesothelin, CD24 and UPAR. This study aims to discover and validate the prognostic significance of a combinatorial panel of tumor biomarkers in patients with resected PDAC. Methods: Patients who underwent PDAC resection were included from a single institution discovery cohort and a multi-institutional validation cohort. Tumors in the discovery cohort were stained immunohistochemically for all nine shortlisted biomarkers. Biomarkers significantly associated with overall survival (OS) were reevaluated as a combinatorial panel in both discovery and validation cohorts for its prognostic significance. Results: 224 and 191 patients were included in the discovery and validation cohorts, respectively. In both cohorts, S100A4, Ca-125 and mesothelin expression were associated with shorter OS. In both cohorts, the number of these biomarkers expressed was significantly associated with OS (discovery cohort 36.8 vs. 26.4 vs 16.3 vs 12.8 months, P &lt; 0.001; validation cohort 25.2 vs 18.3 vs 13.6 vs 11.9 months, P = 0.008 for expression of zero, one, two and three biomarkers, respectively). On multivariable analysis, expression of at least one of three biomarkers was independently associated with shorter OS. Conclusion: Combinations of S100A4, Ca-125 and mesothelin expression stratify survival after resection of localized PDAC. Co-expression of all three biomarkers is associated with the poorest prognostic outcome

Determination of "borderline resectable" pancreatic cancer - A global assessment of 30 shades of grey.

BackgroundPancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a poor prognosis. Accurate preoperative assessment using computed tomography (CT) to determine resectability is crucial in ensuring patients are offered the most appropriate therapeutic strategy. Despite the use of classification guidelines, any interobserver variability between reviewing surgeons and radiologists may confound decisions influencing patient treatment pathways.MethodsIn this multicentre observational study, an international group of 96 clinicians (42 hepatopancreatobiliary surgeons and 54 radiologists) were surveyed and asked to report 30 pancreatic CT scans of pancreatic cancer deemed borderline at respective multidisciplinary meetings (MDM). The degree of interobserver agreement in resectability among radiologists and surgeons was assessed and subgroup regression analysis was performed.ResultsInterobserver variability between reviewers was high with no unanimous agreement. Overall interobserver agreement was fair with a kappa value of 0.32 with a higher rate of agreement among radiologists over surgeons.ConclusionInterobserver variability among radiologists and surgeons globally is high, calling into question the consistency of clinical decision making for patients with PDAC and suggesting that central review may be required for studies of neoadjuvant or adjuvant approaches in future as well as ongoing quality control initiatives, even amongst experts in the field

International Validation of a Nomogram to Predict Recurrence after Resection of Grade 1 and 2 Nonfunctioning Pancreatic Neuroendocrine Tumors

Background: Despite the low recurrence rate of resected nonfunctional pancreatic neuroendocrine tumors (NF-pNETs), nearly all patients undergo long-term surveillance. A prediction model for recurrence may help select patients for less intensive surveillance or identify patients for adjuvant therapy. The objective of this study was to assess the external validity of a recently published model predicting recurrence within 5 years after surgery for NF-pNET in an international cohort. This prediction model includes tumor grade, lymph node status and perineural invasion as predictors. Methods: Retrospectively, data were collected from 7 international referral centers on patients who underwent resection for a grade 1-2 NF-pNET between 1992 and 2018. Model performance was evaluated by calibration statistics, Harrel's C-statistic, and area under the curve (AUC) of the receiver operating characteristic curve for 5-year recurrence-free survival (RFS). A sub-analysis was performed in pNETs >2 cm. The model was improved to stratify patients into 3 risk groups (low, medium, high) for recurrence. Results: Overall, 342 patients were included in the validation cohort with a 5-year RFS of 83% (95% confidence interval [CI]: 78-88%). Fifty-eight patients (17%) developed a recurrence. Calibration showed an intercept of 0 and a slope of 0.74. The C-statistic was 0.77 (95% CI: 0.70-0.83), and the AUC for the prediction of 5-year RFS was 0.74. The prediction model had a better performance in tumors >2 cm (C-statistic 0.80). Conclusions: External validity of this prediction model for recurrence after curative surgery for grade 1-2 NF-pNET showed accurate overall performance using 3 easily accessible parameters. This model is available via www.pancreascalculator.com

Ampullary cancers harbor ELF3 tumor suppressor gene mutations and exhibit frequent WNT dysregulation

The ampulla of Vater is a complex cellular environment from which adenocarcinomas arise to form a group of histopathologically heterogenous tumors. To evaluate the molecular features of these tumors, 98 ampullary adenocarcinomas were evaluated and compared to 44 distal bile duct and 18 duodenal adenocarcinomas. Genomic analyses revealed mutations in the WNT signaling pathway among half of the patients and in all three adenocarcinomas irrespective of their origin and histological morphology. These tumors were characterized by a high frequency of inactivating mutations of ELF3, a high rate of microsatellite instability, and common focal deletions and amplifications, suggesting common attributes in the molecular pathogenesis are at play in these tumors. The high frequency of WNT pathway activating mutation, coupled with small-molecule inhibitors of β-catenin in clinical trials, suggests future treatment decisions for these patients may be guided by genomic analysis

Genomic characterization of malignant progression in neoplastic pancreatic cysts

Intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) are non-invasive neoplasms that are often observed in association with invasive pancreatic cancers, but their origins and evolutionary relationships are poorly understood. In this study, we analyze 148 samples from IPMNs, MCNs, and small associated invasive carcinomas from 18 patients using whole exome or targeted sequencing. Using evolutionary analyses, we establish that both IPMNs and MCNs are direct precursors to pancreatic cancer. Mutations in SMAD4 and TGFBR2 are frequently restricted to invasive carcinoma, while RNF43 alterations are largely in non-invasive lesions. Genomic analyses suggest an average window of over three years between the development of high-grade dysplasia and pancreatic cancer. Taken together, these data establish non-invasive IPMNs and MCNs as origins of invasive pancreatic cancer, identifying potential drivers of invasion, highlighting the complex clonal dynamics prior to malignant transformation, and providing opportunities for early detection and intervention