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Background: The role of portal vein resection for pancreatic cancer is well established but not for pancreatic neuroendocrine neoplasms. Evidence from studies providing information on long-term outcome after venous resection in pancreatic neuroendocrine neoplasms patients is lacking. Methods: This is a multicenter retrospective cohort study comparing pancreaticoduodenectomy with vein resection with standard pancreaticoduodenectomy in patients with pancreatic neuroendocrine neoplasms. The primary endpoint was to evaluate the long-term survival in both groups. Progression-free survival and overall survival were calculated using the method of Kaplan and Meier, but a propensity score-matched cohort analysis was subsequently performed to remove selection bias and improve homogeneity. The secondary outcome was Clavien-Dindo ≥3. Results: Sixty-one (11%) patients underwent pancreaticoduodenectomy with vein resection and 480 patients pancreaticoduodenectomy. Five (1%) perioperative deaths were recorded in the pancreaticoduodenectomy group, and postoperative clinically relevant morbidity rates were similar in the 2 groups (pancreaticoduodenectomy with vein resection 48% vs pancreaticoduodenectomy 33%). In the initial survival analysis, pancreaticoduodenectomy with vein resection was associated with worse 3-year progression-free survival (48% pancreaticoduodenectomy with vein resection vs 83% pancreaticoduodenectomy; P < .01) and 5-year overall survival (67% pancreaticoduodenectomy with vein resection vs 91% pancreaticoduodenectomy). After propensity score matching, no significant difference was found in both 3-year progression-free survival (49% pancreaticoduodenectomy with vein resection vs 59% pancreaticoduodenectomy; P = .14) and 5-year overall survival (71% pancreaticoduodenectomy with vein resection vs 69% pancreaticoduodenectomy; P = .98). Conclusion: This study demonstrates no significant difference in perioperative risk with a similar overall survival between pancreaticoduodenectomy and pancreaticoduodenectomy with vein resection. Tumor involvement of the superior mesenteric/portal vein axis should not preclude surgical resection in patients with locally advanced pancreatic neuroendocrine neoplasms.

Psychology students struggle to recall, recognise or explain how they would select appropriate statistics for common research designs. These selection skills are underpinned by structural awareness, which is the ability to look past the surface (or topic) features of a research design and focus instead on its deep structural characteristics. Although most psychology undergraduates display limited structural awareness, it can be trained. In this pre-registered experiment, we designed and evaluated a novel method of training structural awareness. This training method made use of StatHand, a free iOS and web application, in scaffolded activities designed to highlight how the structural (but not surface) characteristics of a research design determine the selection of an appropriate statistical analysis. Bayesian analyses clearly indicated that this training was effective. Specifically, trained undergraduate psychology students (n = 50) out-performed an un-trained control group (n = 52) on five measures of structural awareness (performance on two sets of triad judgement tasks, two sets of explanation tasks and a scenario generation task) immediately following training, and again one week later (ð = 0.71 to 1.60). At both time points, the trained students also showed greater selection skills than the un-trained control students (ð = 0.52 and 0.57). Finally, on five of these six outcome measures, the trained students showed no decrease in performance between the two time points. Educators are encouraged to consider how they can adapt our methods and materials for deployment in a classroom context or online activities.

The Division of Cancer Prevention of the National Cancer Institute (NCI) and the Office of Disease Prevention of the National Institutes of Health co-sponsored the Translational Advances in Cancer Prevention Agent Development Meeting on August 27 to 28, 2020. The goals of this meeting were to foster the exchange of ideas and stimulate new collaborative interactions among leading cancer prevention researchers from basic and clinical research; highlight new and emerging trends in immunoprevention and chemoprevention as well as new information from clinical trials; and provide information to the extramural research community on the significant resources available from the NCI to promote prevention agent development and rapid translation to clinical trials. The meeting included two plenary talks and five sessions covering the range from pre-clinical studies with chemo/immunopreventive agents to ongoing cancer prevention clinical trials. In addition, two NCI informational sessions describing contract resources for the preclinical agent development and cooperative grants for the Cancer Prevention Clinical Trials Network were also presented.

BACKGROUND AND AIM: Genetic alterations in intrahepatic cholangiocarcinoma (iCCA) are increasingly well characterized, but their impact on outcome and prognosis remains unknown. APPROACH AND RESULTS: This bi-institutional study of patients with confirmed iCCA (n = 412) used targeted next-generation sequencing of primary tumors to define associations among genetic alterations, clinicopathological variables, and outcome. The most common oncogenic alterations were isocitrate dehydrogenase 1 (IDH1; 20%), AT-rich interactive domain–containing protein 1A (20%), tumor protein P53 (TP53; 17%), cyclin-dependent kinase inhibitor 2A (CDKN2A; 15%), breast cancer 1–associated protein 1 (15%), FGFR2 (15%), polybromo 1 (12%), and KRAS (10%). IDH1/2 mutations (mut) were mutually exclusive with FGFR2 fusions, but neither was associated with outcome. For all patients, TP53 (P < 0.0001), KRAS (P = 0.0001), and CDKN2A (P < 0.0001) alterations predicted worse overall survival (OS). These high-risk alterations were enriched in advanced disease but adversely impacted survival across all stages, even when controlling for known correlates of outcome (multifocal disease, lymph node involvement, bile duct type, periductal infiltration). In resected patients (n = 209), TP53mut (HR, 1.82; 95% CI, 1.08–3.06; P = 0.03) and CDKN2A deletions (del; HR, 3.40; 95% CI, 1.95–5.94; P < 0.001) independently predicted shorter OS, as did high-risk clinical variables (multifocal liver disease [P < 0.001]; regional lymph node metastases [P < 0.001]), whereas KRASmut (HR, 1.69; 95% CI, 0.97–2.93; P = 0.06) trended toward statistical significance. The presence of both or neither high-risk clinical or genetic factors represented outcome extremes (median OS, 18.3 vs. 74.2 months; P < 0.001), with high-risk genetic alterations alone (median OS, 38.6 months; 95% CI, 28.8–73.5) or high-risk clinical variables alone (median OS, 37.0 months; 95% CI, 27.6-not available) associated with intermediate outcome. TP53mut, KRASmut, and CDKN2Adel similarly predicted worse outcome in patients with unresectable iCCA. CDKN2Adel tumors with high-risk clinical features were notable for limited survival and no benefit of resection over chemotherapy. CONCLUSIONS: TP53, KRAS, and CDKN2A alterations were independent prognostic factors in iCCA when controlling for clinical and pathologic variables, disease stage, and treatment. Because genetic profiling can be integrated into pretreatment therapeutic decision-making, combining clinical variables with targeted tumor sequencing may identify patient subgroups with poor outcome irrespective of treatment strategy.

OBJECTIVES Pancreatic neuroendocrine neoplasms include well-differentiated tumors (PanNETs) and poorly differentiated carcinomas (PanNECs). Previous reports suggested a role for platinum-based therapy largely in PanNEC. We sought to investigate the role of platinum-based therapy in pancreatic neuroendocrine neoplasms regardless of tumor grade and differentiation. METHODS Patients with pancreatic neuroendocrine neoplasms treated with platinum-based therapy at Memorial Sloan Kettering (1994-2016) and Verona University Hospital (2008-2016) were retrospectively identified. Response to treatment by RECIST v1.1, overall survival, and progression-free survival were defined. Among patients with available tissue, DAXX, ATRX, Rb, and p53 expression was evaluated to support the histologic grade of differentiation. RESULTS Fifty PanNETs, 29 PanNECs, and 22 high-grade tumors with undeterminable differentiation were included. No patients achieved complete response. Overall rate of partial response was 31%, 41% for PanNEC, and 20% for PanNETs. Among PanNETs, partial response was achieved in 33% of G1 (2/6), 10% of G2 (2/19), and 24% of G3 (6/25) tumors. Median overall survival was 29.3 months for PanNETs and 10.9 months for PanNEC (P < 0.001). There was no significant difference in median progression-free survival (P = 0.2). CONCLUSIONS Platinum-based therapies demonstrated increased activity in PanNEC; however, promising efficacy was also observed in PanNETs, irrespective of grade.

Peer-assisted study sessions (PASS) are an international, widely adopted, supplementary instruction programme that has shown to have multiple academic benefits for students. However, PASS attendance rates across the world are typically very low, and the reasons for this are unclear. (1) To test the predictability of the theory of planned behaviour (TPB) on PASS attendance and subsequently students’ academic performance; (2) To assess the role of students’ motivation within the TPB; e.g. can motivation close the intention–behaviour gap and (3) To test whether a large-scale intervention based on the TPB can improve PASS attendance and subsequently improve students’ academic performance. TPB measures, academic motivation, PASS attendance, and final unit grade were assessed three times pre-intervention across two Australian universities (N = 965) and modelled using latent variable analysis. The intervention consisted of a series of ‘PASS Facts’ delivered to students (total N = 2087) via multiple media. The findings showed that the TPB predicted PASS attendance and performance. Academic motivation predicted performance, but it did not close the intention–behaviour gap nor moderate the PASS attendance–performance relationship. Furthermore, in all three implementations, the interventions did not increase the theoretical constructs. The TPB is useful for predicting PASS attendance and can be extended to predict students’ performance. Future research should investigate factors other than academic motivation to attempt to close the intention–behaviour gap. Future research may also develop a more active intervention, wherein students can practice a skill (i.e. time management) instead of passively receiving messages.

The aims of this project were to characterize tiger salamander (Ambystoma tigrinum) spermatozoa motility over time, when excreted as either milt or spermic urine prior to packaging into a spermatophore, and to determine the effect of temperature on sperm motility. A split-plot design was utilized to assess the motility of the two pre-spermatophore sample types at two temperatures, 0°C and 20°C (n = 10 for each treatment). Spermiation was induced through exogenous hormone treatment of luteinizing hormone releasing hormone analog in order to collect both milt and spermic urine, which were evaluated for motility, divided into two separate aliquots, and subsequently stored in either an ice-bath (0°C) or on the benchtop (20°C). The decay rate of sperm motility was assessed by reevaluating subsamples at 0.5, 1, 2, 3, 5, 7, and 24 hours following the initial assessment. Results showed that sperm stored at 0°C had significantly higher progressive, non-progressive, and total motility for both sperm collection types over time. An interaction was found between collection type and time, with milt exhibiting lower initial motility that was more sustainable over time, compared to spermic urine. For both milt and spermic urine, motility decreased rapidly with storage duration, indicating samples should be used as soon as possible to maximize motility for in-vitro fertilization and cryopreservation. This is the first study to describe the differences in sperm motility between milt and spermic urine from an internally fertilizing caudate and demonstrates the benefits of near freezing temperatures on sperm longevity.

Background Pancreatic metastases (PM) from renal cell carcinoma (RCC) are uncommon. We herein describe the long-term outcomes associated with pancreatectomy at two academic institutions, with a specific focus on 10-year survival. Methods This investigation was limited to patients undergoing pancreatectomy for PM between 2000 and 2008 at the University of Verona and Memorial Sloan Kettering Cancer Center, allowing a potential for 10 years of surveillance. The probabilities of further RCC recurrence and RCC-related death were estimated using a competing risk analysis (method of Fine and Gray) to account for patients who died of other causes during follow-up. Results The study population consisted of 69 patients, mostly with isolated metachronous PM (77%). The median interval from nephrectomy to pancreatic metastasectomy was 109 months, whereas the median post-pancreatectomy follow-up was 141 months. The 10-year cumulative incidence of new RCC recurrence was 62.7%. In the adjusted analysis, the relative risk of repeated recurrence was significantly higher in PM synchronous to the primary RCC (sHR = 1.27) and in patients receiving extended pancreatectomy (sHR = 3.05). The 10-year cumulative incidence of disease-specific death was 25.5%. The only variable with an influence on disease-specific death was the recurrence-free interval following metastasectomy (sHR = 0.98). In patients with repeated recurrence, the 10-year cumulative incidence of RCC-related death was 35.4%. Conclusion In a selected group of patients followed for a median of 141 months and mostly with isolated metachronous PM, resection was associated with a high possibility of long-term disease control in surgically fit patients with metastases confined to the pancreas.

PURPOSE: To evaluate the associations between computed tomography (CT) imaging features extracted from the structured American Pancreatic Association (APA)/Society of Abdominal Radiology (SAR) template and overall survival in patients with resected pancreatic ductal adenocarcinoma (PDAC). METHODS: This retrospective analysis included consecutive patients with PDAC who consented to genomic tumor testing and underwent preoperative imaging and curative intent surgical resection from December 2006 to July 2017. Two radiologists assessed preoperative CT imaging using the APA/SAR PDAC reporting template. Univariable associations between overall survival and imaging variables were evaluated using Cox proportional hazards regression. RESULTS: The study included 168 patients (66 years ± 11; 91 women). 126/168 patients (75%) received upfront surgical resection whereas 42/168 (25%) received neoadjuvant therapy prior to surgical resection. In the entire cohort, features associated with decreased overall survival were tumor arterial contact of any kind (hazard ratio (HR) 1.89, 95% CI 1.13–3.14, p=0.020), tumor contact with the common hepatic artery (HR 2.33, 95% CI 1.35–4.04, p=0.009) and portal vein deformity (HR 3.22, 95% CI 1.63–6.37, p=0.003). In the upfront surgical group, larger tumor size was associated with decreased overall survival (HR 2.30, 95% CI 1.19–4.42, p=0.013). In the neoadjuvant therapy group, the presence of venous collaterals was the only feature associated with decreased overall survival (HR 2.28, 95% CI 1.04–4.99, p=0.042). CONCLUSION: The application of the APA/SAR pancreatic adenocarcinoma reporting template may identify predictors of survival that can aid in preoperative stratification of patients.

Effective communication is a generic competency essential to clinical practice. However, access to work-integrated placements where such competencies are traditionally developed is diminishing, compelling universities to develop supplementary placement opportunities in the form of simulated learning environments (SLE). Virtual or digital patient (VP) placements are an attractive SLE model, but evidence of their efficacy for developing student communication competence is limited. In the current study, 82 second-year undergraduate speech pathology students completed one half-day placement, requiring them to use conversation interaction skills to build rapport with a VP across two 10-minute interactions, separated by clinical educator (CE) feedback and self-reflection. Each student’s interactions were rated by CEs on 25 communication competencies and, following the second interaction, students completed retrospective pre-placement and post-placement self-ratings of their communication skills, knowledge and confidence. CEs’ ratings of students’ performance were significantly higher following the second interaction than they were following the first (median ηp2 = .710). Furthermore, the students’ post-placement self-ratings were significantly higher than their retrospective pre-placement ratings (median dav = 1.25). These findings suggest that VP placements as simulated clinical learning opportunities support speech pathology education, and may have positive implications for all health professions.

Background The aim of the present study was to evaluate the impact of routine NGT decompression after PD on postoperative outcomes in the era of an enhanced recovery after surgery (ERAS) protocol. Materials and methods A retrospective review of all patients undergoing PD between January 2015 and October 2017 at our institution was performed comparing routine post-operative NGT decompression versus omission. The incidence of delayed gastric emptying, post-operative pancreatic fistula, hospital length of stay, operative time, 30-day readmission rate as well the time to first oral intake were evaluated. Results Out of 149 patients who underwent PD, 65 maintained post-operative NGT decompression while post-operative NGT decompression was omitted in 84 patients. No differences were noted in delayed gastric emptying rates (both p>0.05). The median length of stay (9 days for NGT group versus 8.5 days for no NGT group) and 30-day readmission rates (13.8% versus 15.5%, respectively) were similar (p=0.781). Compared with patients who had routine post-operative NGT placed, those who had omission of a post-operative NGT had a lower need for reinsertion, shorter time to PO intake, and a lower likelihood of extended length of stay. Conclusions In the era of ERAS protocols, we observed no association between routine post-operative NGT decompression after PD and improved postoperative outcomes.

MINI: Patients with colorectal liver metastases and available KRAS data treated with resection and with or without adjuvant hepatic artery infusion chemotherapy were retrospectively evaluated. Adjuvant hepatic artery infusion was independently associated with improved outcomes regardless of KRAS mutational status. Adjuvant hepatic artery infusion may mitigate the worse outcomes seen in patients with resectable KRAS-MUT CRLM. OBJECTIVE To investigate the impact of adjuvant hepatic artery infusion (HAI) in relation to KRAS mutational status in patients with resected colorectal cancer liver metastases (CRLM). BACKGROUND Patients with KRAS-mutated CRLM have worse outcomes after resection. Adjuvant HAI chemotherapy improves overall survival after liver resection. METHODS Patients with resected CRLM treated at MSKCC with and without adjuvant HAI who had available KRAS status (wild-type, WT; mutated, MUT) were reviewed from a prospectively maintained institutional database. Correlations between KRAS status, adjuvant HAI, clinical factors, and outcomes were analyzed. Cox proportional hazard model was used to adjust for confounders. RESULTS Between 1993 and 2012, 674 patients (418 KRAS-WT, 256 MUT) with a median follow up of 6.5 years after resection were evaluated. Fifty-four percent received adjuvant HAI. Tumor characteristics (synchronous disease, number of lesions, clinical-risk score, 2-stage hepatectomy) were significantly worse in the HAI group; however, there were more patients with resected extrahepatic metastases in the no-HAI group. In KRAS-WT tumors, 5-year survival was 78% for patients treated with HAI versus 57% for patients without HAI [hazard ratio (HR) 0.51, P < 0.001]. In KRAS-MUT tumors, 5-year survival was 59% for patients treated with HAI versus 40% for patients without HAI (HR 0.56, P < 0.001). On multivariate analysis, HAI remained associated with improved OS (HR 0.53, P < 0.002) independent of KRAS status and other clinicopathologic factors. CONCLUSION Adjuvant HAI after resection of CRLM is independently associated with improved outcomes regardless of KRAS mutational status. Adjuvant HAI may mitigate the worse outcomes seen in patients with resectable KRAS-MUT CRLM.

Background and AimsA subset of pancreatic ductal adenocarcinomas (PDACs) is highly resistant to systemic chemotherapy, but no markers are available in clinical settings to identify this subset. We hypothesized that chemotherapy-resistant PDACs express a glycan biomarker called sTRA. Methods. We tested this marker to identify treatment-resistant PDAC in multiple systems: sets of cell lines, organoids, and isogenic cell lines; primary tumors; and blood plasma from cohorts of human subjects. Results. Among a panel of 27 cell lines, high levels of cell-surface sTRA identified higher resistance to seven chemotherapeutics used against PDAC. Using primary tumors from two different cohorts, patients who were positive for a gene-expression classifier for sTRA received no statistically significant benefit from adjuvant chemotherapy, in contrast to those negative for the signature. In another cohort, using direct measurements of sTRA in tissue microarrays by quantitative immunofluorescence, patients who were high in sTRA again had no statistically significant benefit from adjuvant chemotherapy. Further, a blood-plasma test for the sTRA glycan identified the PDACs that showed rapid relapse following neoadjuvant chemotherapy. This blood test performed with 96% specificity and 56% sensitivity in a blinded cohort using samples collected before the start of treatment. Conclusion. These findings establish that tissue or plasma sTRA can identify PDACs that are resistant to neoadjuvant or adjuvant chemotherapy. This capability could help apply systemic treatments more precisely and facilitate biomarker-guided trials targeting resistant PDAC.

This paper contributes to the burgeoning field of surgical data science. Specifically, multi-modal integration of relevant patient data is used to determine who should undergo a complex pancreatic resection. Intraductal papillary mucinous neoplasms (IPMNs) represent cystic precursor lesions of pancreatic cancer with varying risk for malignancy. We combine radiomic analysis of diagnostic computed tomography (CT) with protein markers extracted from the cyst fluid to create a unified prediction model to identify high-risk IPMNs. Patients with high-risk IPMN would be sent for resection, whereas patients with low-risk cystic lesions would be spared an invasive procedure. We extracted radiomic features from CT scans and combined this with cyst-fluid markers. The cyst fluid model yielded an area under the curve (AUC) of 0.74. Adding the QI model improved performance with an AUC of 0.88. Radiomic analysis of routinely acquired CT scans combined with cyst fluid inflammatory markers provides accurate prediction of risk of pancreatic cancer progression.

Hepatic artery infusion (HAI) combined with systemic chemotherapy is a treatment strategy for patients with unresectable liver-only or liver-dominant colorectal liver metastases (CRLM). Although HAI has previously been performed in only a few centers, this study aimed to describe patient selection and initial perioperative outcomes during implementation of a new HAI program.The study enrolled patients with CRLM selected for HAI after multi-disciplinary review November 2018-January 2020. Demographics, prior treatment, and perioperative outcomes were assessed. Objective hepatic response was calculated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.During a 14-month period, 21 patients with CRLM underwent HAI pump placement. Of these 21 patients, 20 (95%) had unresectable disease. Most of the patients had synchronous disease (n = 18, 86%) and had received prior chemotherapy (n = 20, 95%) with extended treatment cycles (median 16; interquartile range, 8-22; range, 0-66). The median number of CRLMs was 7 (range, 2-40). Operations often were performed with combined hepatectomy (n = 4, 19%) and/or colectomy/proctectomy (n = 11, 52%). The study had no 90-day mortality. The overall surgical morbidity was 19%. The HAI-specific complications included pump pocket seroma (n = 2), hematoma (n = 1), surgical-site infection (n = 1), and extrahepatic perfusion (n = 1). HAI was initiated in 20 patients (95%). The hepatic response rates at 3 months included partial response (n = 4, 24%), stable disease (n = 9, 53%), and progression of disease (n = 4, 24%), yielding a 3-month hepatic disease control rate (DCR) of 76%.Implementation of a new HAI program is feasible, and HAI can be delivered safely to selected patients with CRLM. The initial response and DCR are promising, even for patients heavily pretreated with chemotherapy.

Background KRAS, TP53, CDKN2A, and SMAD4 are established driver genes in pancreatic ductal adenocarcinoma (PDAC). This study was aimed at determining whether the mutational status of driver genes and those involved in DNA repair pathways are associated with clinical outcomes for individuals who undergo resection. Methods Eligible individuals were those who underwent resection of PDAC and consented to targeted sequencing of their primary tumor via Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT). Genomic alterations were determined on the basis of MSK-IMPACT results from formalin-fixed, paraffin-embedded samples. Associations between genomic alterations and clinical outcomes were assessed. Results Targeted sequencing was performed on 283 primary tumors resected between 2004 and 2017. The median follow-up was 23 months among survivors. Alterations in KRAS and TP53 were associated with worse overall survival (OS) in comparison to wild type (median for KRAS, 38.8 months [95% CI, 33.0-45.5 months] vs 91.0 months [95% CI, 34.8 months to not available (NA)]; P = .043; median for TP53, 37.4 months [95% CI, 32.1-42.8 months] vs 65.0 months [95% CI, 33.0 months to NA]; P = .035). KRAS G12D mutations were associated with worse OS (median, 31.6 months [95% CI, 25.3-45.5 months] vs 39.2 months [95% CI, 37.4-75.2 months]; P = .012). TP53 truncating mutations (median, 39.6 months [95% CI, 32.4-75.2 months] vs 33.9 months [95% CI, 24.0-39.0 months]; P = .020) and those associated with loss of heterozygosity (median, 26.6 months [95% CI, 21.6-44.2 months] vs 39.2 months [95% CI, 34.5-49.1 months]; P = .048) had decreased OS. TP53 alterations were independently associated with OS in a multivariate analysis (hazard ratio, 1.54; 95% CI, 1.01-2.33; P = .042). Individuals with germline alterations in homologous recombination deficiency (HRD) genes had improved OS in comparison with those without them (median, not reached vs 37.0 months; 95% CI, 33.0-49.8 months; P = .035). Conclusions In patients with resected PDAC, genomic alterations in KRAS and TP53 are associated with worse outcomes, whereas alterations in HRD genes are associated with a favorable prognosis. Further studies are needed to better define these alterations as biomarkers in resected PDAC.

Acute (< 96 h) exposure to elevated environmental CO2 (hypercarbia) induces a pH disturbance in fishes that is often compensated by concurrent recovery of intra- and extracellular pH (pHi and pHe, respectively; coupled pH regulation). However, coupled pH regulation may be limited at PCO2 tensions far below levels that some fishes naturally encounter. Previously, four hypercarbia tolerant fishes had been shown to completely and rapidly regulate heart, brain, liver, and white muscle pHi during acute exposure to>4 kPa PCO2 (preferential pHi regulation) before pHe compensation was observed. Here we test the hypothesis that preferential pHi regulation is a wide spread strategy of acid-base regulation among fish by measuring pHi regulation in 10 different fish species that are broadly phylogenetically separated, spanning 6 orders, 8 families and 10 genera. Contrary to previous views, we show that preferential pHi regulation is the most common strategy for acid-base regulation within these fishes during exposure to severe acute hypercarbia and that this strategy is associated with increased hypercarbia tolerance. This suggests preferential pHi regulation may confer tolerance to the respiratory acidosis associated with hypercarbia and we propose that it is an exaptation that facilitated key evolutionary transitions in vertebrate evolution, such as the evolution of air breathing.

120 Background: Hepatic artery infusion (HAI) is a liver directed therapy to treat unresectable or resected colorectal liver metastases (CRLM) and unresectable intrahepatic cholangiocarcinoma (ICC). Historically, HAI has only been performed at few specialized centers; however, there is increasing expansion to new centers. We previously reported safety outcomes of our index year of HAI therapy. We now report safety, feasibility, efficacy and oncologic outcomes for an expanded cohort of 62 patients in an established HAI program. Methods: Patients selected for HAI by multidisciplinary review were evaluated for demographics and perioperative outcomes. Objective hepatic response was calculated according to RECIST 1.1. Overall, hepatic and extrahepatic progression-free survival (PFS) were calculated by the Kaplan-Meier method on an intent-to-treat basis. Results: 62 patients were treated with HAI from November 2018-September 2021: 46 for unresectable CRLM, 8 as adjuvant HAI for resected CRLM, and 8 for unresectable ICC. Median age was 54.5 years (range 32-80), 58% were male, and 97% received prior chemotherapy (median 12 cycles, range 0-66). Hepatectomy (18, 29%) and/or colectomy/proctectomy (27, 43.5%) was performed concurrently with pump placement, and 19 (30.6%) were performed robotically. Median operating time was 265 minutes (range 130-526), estimated blood loss was 100 mL (range 22-1000) and length of stay was 5 days (range 1-19). HAI-specific complications occurred in 14% (Table). Floxuridine (FUDR) was initiated in 95% of patients a median of 18.5 days after surgery. Of the 38 patients who received HAI for unresectable CRLM and had measurable disease on imaging, 3- and 6-month hepatic disease control was achieved in 86% (8 partial response [PR], 22 stable disease [SD], 5 progressed [PD]) and 89% (1 complete response, 8 PR, 8 SD, 2 PD), respectively. For patients with at least 3 months follow-up, median PFS, hepatic PFS and extrahepatic PFS were 13 months, 13 months, and 13 months, respectively. Conclusions: HAI can be safely and effectively delivered to well-selected patients with CRLM and ICC. Response rates, disease control and PFS in heavily treated patients with unresectable CRLM comparable to high-volume centers can be achieved at new programs with appropriate expertise. These data support the mission of the newly formed HAI Consortium to critically evaluate efficacy and innovation in HAI therapy through multi-institutional collaboration and contemporary prospective trials.[Table: see text]

Understanding environmental constraints and associated physiological adaptations of culture organisms is key for the implementation of off-shore grow-out facilities. In the southeast Pacific Ocean along the coasts of Chile and Peru, seasonal upwelling events lead to hypoxic conditions, which are projected to increase in both frequency and intensity with climate change. Aquaculture operations must take into account the physiological adaptability of a species for environmental conditions. For Cojinoba (Seriolella violacea), a native target species for aquaculture diversification in northern Chile, little is known in regard to physiological capacity for hypoxia. Therefore, hypoxia tolerance studies were conducted followed by measurement of resting and active metabolism and associated energy facilitation in response to hypoxia in juvenile Cojinoba. Hypoxia tolerance studies found they were resilient to dissolved oxygen levels of 1.0 mg O2 Lˉ1 for 8 h. Swimming metabolism studies exposed Cojinoba to normoxia (7.5 mg O2 Lˉ1) or hypoxia (1.0 mg O2 Lˉ1), and quantified minimum metabolic rate (MO2 min), active metabolic rate (MO₂ max), critical swimming speed (Ucrit) and associated energetic metabolites and hematological variables. In hypoxia, there was a decrease in MO₂ max (34%) leading to a large (82%) decrease in aerobic metabolic scope. MO2 min decreased as well by 12%, with lactate increasing presumably to temporarily maintain basic metabolic function. In addition, Ucrit decreased by 53% in hypoxia, although tail beat frequency was similar in normoxia and hypoxia up to a velocity of 40 cm s−1. Moreover, although erythrocyte concentration increased in hypoxia, hemolysis was observed in exercised fish in this condition. There was a notable increase (5-fold compared to normoxia) in lactate levels of exercised fish in the hypoxia group, which suggests a quick conversion to anaerobic metabolic pathways to maintain energy balance when swimming in hypoxic environments. Therefore, Cojinoba have adaptive responses that may facilitate survival during severe hypoxic events although overall physiological performance is diminished.

Background Low central venous pressure (LCVP) anesthesia reduces blood loss during hepatic resection and historically has required a central venous catheter (CVC) for intra-operative monitoring. The aim of this study was to assess the effect of an evolution of practice to CVP monitoring without CVC on the perioperative outcomes after liver resection. Methods A retrospective study of partial hepatectomy patients from 2007 to 2016 who were over 18 years of age was performed. Results Of 3903 patients having partial hepatectomy, 2445 (62%) met inclusion criteria, and 404 (16%) had a CVC. Overall morbidity (33% non-CVC vs 38% CVC P = 0.076), major morbidity (16% vs 20% P = 0.067), and infective complications (superficial wound infection) 3% vs 4% P = 0.429; deep wound infection (5% vs 6% P = 0.720) did not differ between the two groups. In multivariate analysis, superficial wound infection, deep wound infection, and major complications were not associated with the presence of a CVC. All-cause mortality at 90 days was associated with CVC presence (OR 3.45, CI 1.74–6.85, P = 0.001) and age (OR 1.05, CI 1.02–1.08, P Conclusion Since the adoption of non-invasive CVP monitoring, there has been no increase in adverse peri-operative outcomes.

Tailwater recovery (TWR) systems are being implemented on agricultural landscapes to reduce nutrient loss and save water on the landscape for irrigation. These systems are a large financial investment for both the United States Department of Agriculture Natural Resources Conservation Service (USDA NRCS) and private producers with total costs ranging from $400,000 to 900,000. Although economic analyses of TWR systems have been modeled, analyses of implemented TWR systems have yet to be completed. Economic studies are necessary to guide adaptive management of conservation funding for appropriation in methods with the greatest return. Therefore, an analysis was conducted on the costs and benefits of TWR systems by first comparing net present value (NPV) and benefit-to-cost ratios (BCR) of operation scenarios with and without TWR systems, as well as, with and without sediment reduction benefits. Second, the impact of the level of USDA NRCS financial assistance on NPV was evaluated. Three discount rates of 3, 7, and 10% were used on both rented and owned land schemes. Five TWR system scenarios were used in the investigation including dryland, irrigated, irrigation improvements, TWR systems, and TWR systems with external benefits of sediment loss mitigation. NPV and BCRs were positive and greater than one for TWR systems if producers owned the land but remained negative or less than one if land was rented. Beyond improvements to irrigation infrastructure, farms with a TWR system installed lost NPV of $51 to $328 per ha. Therefore, TWR systems are not considered to be economically viable when land is not owned.

Populations of Black Buffalo Ictiobus niger, a broadly-distributed catostomid species native to the Mississippi River basin, are in decline, similar to many other catostomids. Artificial propagation and culture are frequently a part of native species recovery plans, and developing formulated diets is a critical component of these plans. However, studies establishing protein requirements for catostomids are limited, particularly for larger juvenile to sub-adult sizes, even though catostomids are commonly reared to these sizes. Therefore, we conducted a 10-week growth study to evaluate optimal protein levels in juvenile (age-1) Black Buffalo (mean ± SE: total length = 218.7 ± 0.8 mm, weight = 148.5 ± 1.6 g). Five practical diets were formulated to contain 30, 34, 38, 41, and 45% crude protein with each diet fed to four replicate tanks (400-L) containing 10 fish each. Fish fed a diet containing 41% crude protein had greater biomass gain (total weight gain for all fish in the tank) when compared to other diets. Individual weight gain (percent increase) was greater in fish fed diets containing 41% and 45% protein compared to lower protein diets. Results from this study suggest a diet with 41% crude protein would produce optimal growth for juvenile (age-1) Black Buffalo.

BACKGROUND: Elevation in the serum immunoglobulin-G4 (IgG4) level has been used as a diagnostic marker to distinguish autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDAC), but its true utility is ill-defined. This study evaluates the clinical utility of IgG4 in differentiating AIP from PDAC. METHODS: All patients evaluated in the hepatopancreaticobiliary surgery clinics with measured serum IgG4 were included. Patients were divided into normal IgG4 (

Trace element and 87Sr/86Sr isotope analyses of fish pectoral fin rays offer non-destructive methods for determining habitat use. In this study, water and fin ray samples were analyzed for Gulf Sturgeon Acipenser oxyrinchus desotoi from the Choctawhatchee River Basin (FL and AL, USA) and compared with reference samples from Atlantic Sturgeon A. o. oxyrinchus held at controlled salinities (0, 10, 33 ppt). Samples were analyzed using inductively coupled plasma mass spectrometry, with a multi-collector for 87Sr/86Sr. In water, Sr, Ba, Mn and Zn differed between freshwater and saline habitats, with increases in Sr and decreases in Ba, Mn and Zn. 87Sr/86Sr decreased upstream to downstream with lowest values in saline habitats. In the reference study, water trace element concentrations and 87Sr/86Sr corresponded to those in pectoral fin rays. 87Sr/86Sr was higher in pectoral fin ray than water, due to influence of diet, which differed with salinity. In wild fish, trace elements in pectoral fin rays indicated freshwater emigration to saline habitats primarily occurred in the second to third growth zone with some heterogeneity in the population (4%

Best management practices are being implemented throughout the Lower Mississippi River Alluvial Valley with the aim of alleviating pressures placed on downstream aquatic systems by sediment and nutrient losses from agricultural land; however, research evaluating the performance of tailwater recovery (TWR) systems, an increasingly important practice, is limited. This study evaluated the ability of TWR systems to retain sediment and nutrients draining from agricultural landscapes. Composite flow-based samples were collected during flow events (precipitation or irrigation) over a two-year period in six TWR systems. Performance was evaluated by comparing concentrations and loads in water entering TWR systems (i.e., runoff or influent) from agricultural fields to water overflow exiting TWR systems (effluent). Tailwater recovery systems did not reduce concentrations of solids and nutrients, but did reduce loads of solids, phosphorus (P), and nitrogen (N) by 43%, 32%, and 44%, respectively. Annual mean load reductions were 1,142 kg solids, 0.7 kg of P, and 3.8 kg of N. Performance of TWR systems was influenced by effluent volume, system fullness, time since the previous event, and capacity of the TWR system. Mechanistically, TWR systems retain runoff on the agricultural landscape, thereby reducing the amount of sediment and nutrients entering downstream waterbodies. System performance can be improved through manipulation of influential parameters.

PURPOSE: Clinician gestalt may hold unexplored information that can be capitalized upon to improve existing nomograms. The study objective was to evaluate physician ability to predict 2-year overall survival (OS) in resected pancreatic ductal adenocarcinoma (PDAC) patients based on preoperative clinical characteristics and routine CT imaging. METHODS: Ten surgeons and two radiologists were provided with a clinical vignette (including age, gender, presenting symptoms, and pre-operative CA19-9 when available) and preoperative CT scan for 20 resected PDAC patients and asked to predict the probability of each patient reaching 2-year OS. Receiver operating characteristic curves were used to assess agreement and to compare performance with an established institutional nomogram. RESULTS: Ten surgeons and 2 radiologists participated in this study. The area under the curve (AUC) for all physicians was 0.707 (95%CI 0.642–0.772). Attending physicians with >5 years experience performed better than physicians with

Pancreatic adenocarcinoma is associated with poor overall prognosis. Complete surgical resection is the only possible option for cure. As such, increasingly complex surgical techniques including sophisticated vascular reconstruction are being used. Continued advances in surgical techniques, in conjunction with use of combination systemic therapies, and radiation therapy have been suggested to improve outcomes. A key aspect to surgical success is reporting of pivotal findings beyond absence of distant metastases, such as tumor size, location, and degree of tumor involvement of specific vessels associated with potential perineural tumor spread. Multiphase contrast-enhanced multidetector CT and MRI are the imaging modalities of choice for pretreatment staging and presurgical determination of resectability. Imaging modalities such as endoscopic ultrasound and fluorine-18-2-fluoro-2-deoxy-D-glucose imaging with PET/CT are indicated for specific scenarios such as biopsy guidance and confirmation of distant metastases, respectively. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Crappie, Pomoxis spp., are popular game fish throughout North America and are produced by public and private hatcheries. However, production is limited by a lack of information on tank culture and induced spawning methods. Development of techniques for storage of sperm and in vitro fertilization would increase flexibility in spawning. Therefore, techniques for sperm cryopreservation were examined in white crappie, Pomoxis annularis. Sperm from adult wild white crappie were used to evaluate sperm extender, cryoprotectant agent and concentration, and cooling technique based on post-thaw sperm motility. Percent egg fertilization was also compared between sperm stored in the two best cryopreservation protocols and two different osmotic activator solutions. Sperm were cryopreserved using treatment combinations of two extenders (350 mOsmol/kg Hanks' balanced salt solution [HBSS] and 350 mOsmol/kg Ca2+free HBSS) and two cryoprotectants (dimethyl sulfoxide [DMSO] and methanol) at concentrations of 5, 10, and 15% that were cooled at four different rates: 5, 10, 20, and 40 C/min. Post-thaw sperm motility and fertilization rates indicated white crappie sperm can be cryopreserved using either extender, cryoprotectants of either 5% DMSO or 10% methanol, and cooling at 40 C/min. A follow-up experiment demonstrated sperm in suspensions on ice retained viability after overnight transport.

Within the Lower Mississippi Alluvial Valley, conservation practices are being utilized to mitigate nutrient loading to streams from agricultural landscapes. This study was conducted to determine the potential to use solids, phosphorus (P) and nitrogen (N) captured by tailwater recovery (TWR) systems for reuse onto production fields through irrigation applications. Seven TWR systems were assessed for seasonal changes in nutrient concentrations and application loads. Samples were collected every three weeks from 2013 to 2015 for seasonal analyses and weekly during the 2014 and 2015 growing seasons for nutrient load analyses. Water samples collected in spring contained greater concentrations of solids than samples collected in winter and summer. In addition, spring samples contained greater concentrations of nitrate–nitrite than samples collected in all other seasons, and spring samples also contained higher ammonium than summer and fall samples. Mean nutrient loads per hectare recycled onto the landscape for an irrigation season were 325.10 kg ha−1 solids, 0.86 kg ha−1 P, and 7.26 kg ha−1 N, with the N being 77% organic. TWR systems can be used to recycle solids, P and N onto agricultural landscapes through irrigation events; however, nutrient loads will not be sufficient to alter agronomic fertilizer recommendations.

Proteomics can be used to characterize quality defects including pale, soft, and exudative (PSE) meat (pork and poultry), woody broiler breast meat, reddish catfish fillets, meat toughness, and beef myoglobin oxidation. PSE broiler meat was characterized by 15 proteins that differed in abundance in comparison to normal broiler breast meat, and eight proteins were differentially expressed in woody breast meat in comparison to normal breast meat. Hemoglobin was the only protein that was differentially expressed between red and normal catfish fillets. However, inducing low oxygen and/or heat stress conditions to catfish fillets did not lead to the production of red fillets. Proteomic data provided information pertaining to the protein differences that exist in meat quality defects. However, these data need to be evaluated in conjunction with information pertaining to genetics, nutrition, environment of the live animal, muscle to meat conversion, meat quality analyses and sensory attributes to understand causality, protein biomarkers, and ultimately how to prevent quality defects.

In 2015, the American Gastroenterological Association recommended the discontinuation of radiographic surveillance after 5 years for patients with stable pancreatic cysts. The current study evaluated the yield of continued surveillance of pancreatic cysts up to and after 5 years of follow up.A prospectively maintained registry of patients evaluated for pancreatic cysts was queried (1995-2016). Patients who initially underwent radiographic surveillance were divided into those with5 years and ≥5 years of follow up. Analyses for the presence of cyst growth (5 mm increase in diameter), cross-over to resection, and development of carcinoma were performed.A total of 3024 patients were identified, with 2472 (82%) undergoing initial surveillance. The ≥5 year group (n = 596) experienced a greater frequency of cyst growth (44% vs. 20%; P0.0001), a lower rate of cross-over to resection (8% vs 11%; P = 0.02), and a similar frequency of progression to carcinoma (2% vs 3%; P = 0.07) compared with the5 year group (n = 1876). Within the ≥5 year group, 412 patients (69%) had demonstrated radiographic stability at the 5-year time point. This subgroup, when compared with the5 year group, experienced similar rates of cyst growth (19% vs. 20%; P= 0.95) and lower rates of cross-over to resection (5% vs 11%; P0.0001) and development of carcinoma (1% vs 3%; P= 0.008). The observed rate of developing cancer in the group that was stable at the 5-year time point was 31.3 per 100,000 per year, whereas the expected national age-adjusted incidence rate for this same group was 7.04 per 100,000 per year.Cyst size stability at the 5-year time point did not preclude future growth, cross-over to resection, or carcinoma development. Patients who were stable at 5 years had a nearly 3-fold higher risk of developing cancer compared with the general population and should continue long-term surveillance.

Major liver resection for perihilar cholangiocarcinoma (PHC) is associated with a 22% to 33% postoperative liver failure incidence. The aim of this study was analyze the predictive value of future liver remnant (FLR) volume for postoperative liver failure after resection for PHC and to develop a risk score to improve patient selection for portal vein embolization. A consecutive series of 217 patients underwent major liver resection for PHC between 1997 and 2014 at 2 Western centers; FLR volumes were calculated with CT volumetry; other variables included jaundice at presentation, immediate preoperative bilirubin, and preoperative cholangitis. The FLR volume was categorized as 45%. A risk score for postoperative liver failure (grade B/C according to the International Study Group of Liver Surgery criteria) was developed using multivariable logistic regression with 5 predefined variables. Postoperative liver failure incidence was 24% and liver failure-related mortality was 12%. Risk factors for liver failure were FLR volume 50 μmol/L (>2.9 mg/dL) (odds ratio 4.3; 95% CI 1.7 to 10.7), and preoperative cholangitis (odds ratio 3.4; 95% CI 1.6 to 7.4) were risk factors for liver failure. These variables were included in a risk score that showed good discrimination (area under the curve 0.79; 95% CI 0.72 to 0.86) and ranking patients in 3 risk sub-groups with predicted liver failure incidence of 4%, 14%, and 44%. The selection of patients for portal vein embolization using only liver volume is insufficient, considering the other predictors of liver failure in PHC patients. The proposed risk score can be used for selection of patients for portal vein embolization, for adequate patient counseling, and identification of other modifiable risk factors besides liver volume

Poor oral health appears to be a risk factor for pancreatic cancer, possibly implicating the oral microbiota. In this pilot study, we evaluated the characteristics of the oral microbiota in patients with pancreatic ductal adenocarcinoma (PDAC), intraductal papillary mucinous neoplasms (IPMN), and healthy controls. Forty newly diagnosed PDAC patients, 39 IPMN patients, and 58 controls, excluding current smokers and users of antibiotics, provided saliva samples. Common oral bacterial species were comprehensively surveyed by sequencing of the 16S rRNA microbial genes. We obtained measures of diversity and the mean relative proportions of individual taxa. We explored the degree to which these measures differed according to respondent characteristics based on individual interviews. PDAC cases did not differ in diversity measures from either controls or IPMN cases. PDAC cases had higher mean relative proportions of Firmicutes and related taxa, while controls had higher mean relative proportions of Proteobacteria and related taxa. Results were generally similar when comparing PDAC to IPMN cases. Among IPMNs and controls combined, younger individuals had higher levels of several taxa within the Proteobacteria. The only other variable consistently related to mean relative proportions was mouthwash use, with taxa within Firmicutes more common among users. While there were no differences in diversity of the oral microbiota among these groups, there were differences in the mean relative proportions of some taxa. Characteristics of the oral microbiota are not associated with most measures of oral health.

The alligator gar Atractosteus spatula is a primitive fish species, occupying a wide range of temperature and salinity habitats. Long-distance movements are limited, leading to genetic differentiation between inland and coastal populations. Unknown is whether physiological capacity differs between geographically separated populations, particularly for traits important to osmoregulation in saline environments. Alligator gar from inland and coastal populations were reared in a similar environment and exposed to temperature (10, 30 °C) and salinity (0, 20 ppt) extremes to determine whether iono- and osmoregulatory ability differed between populations. There were few differences in osmoregulatory ability between populations, with similar gill, blood and gastrointestinal tract osmoregulatory parameters. Blood plasma osmolality, ion concentrations, intestinal pH and bicarbonate base concentrations, intestinal fluid osmolality, ion concentrations and gill Na+, K+-ATPase (NKA) activity were similar between populations. Notably, gar from both populations did not osmoregulate well at low temperature and high salinity, with elevated plasma osmolality and ion concentrations, low gill NKA, and little evidence of gastrointestinal tract contribution to ionic and base regulation based on a lack of intestinal fluid and low base content. Therefore, the hypothesis that coastal gar would have improved osmotic regulatory ability in saline environments as compared to inland alligator gar was not supported, suggesting physiological capacity may be retained in primitive species possibly due to its importance to their persistence through time.

Re-operation is advised for patients with T1b or greater incidental gallbladder cancer (GBCA). The presence of residual disease (RD) impacts resectability, chemotherapy, and survival. This study created a preoperative model to predict RD at re-operation. Patients with re-operation for incidental GBCA from 1992–2015 were included. The relationship between pathology data from initial cholecystectomy and RD at re-operation was assessed with logistic regression and classification and regression tree (CART) analysis. Two hundred fifty-four patients were included and 188 underwent definitive re-resection (74.0%). Distant RD was identified in 69 (27.2%) patients and locoregional only RD in 82 (32.3%). On multivariate analysis, T3 (OR 22.7, 95% CI 5.5–94.4) and poorly differentiated tumors (OR 4.3, 95% CI 1.4–13.3) were associated with RD (p

Background Preoperative chemotherapy is a strategy for converting to resection and/or assessing disease biology before operation. The utility of such an approach in gallbladder carcinoma (GBCA) is unknown. This study evaluated outcomes of GBCA patients treated with chemotherapy for locally advanced or lymph node-involved tumors. Study Design Patients who received systemic chemotherapy for locally advanced or lymph node-positive GBCA were identified from a departmental database. Patients were excluded if there was any evidence of distant metastases or if records were inadequate to determine initial chemotherapy and response. Response Evaluation Criteria in Solid Tumors (RECIST), operative results, and overall survival (OS) were assessed. Results Seventy-four patients were included, from 1992 to 2015. Eighty-nine percent of patients (n = 64) were treated with gemcitabine and 57% with gemcitabine/platinum (n = 42). At initial response assessment, 17 patients (23%) had progression. The remaining patients had stable disease (n = 38, 51%) or partial response (n = 19, 26%). Twenty-two patients (30%) underwent attempt at resection, which was definitive for 10 patients (14%). Median OS for the entire cohort was 14 months (95% CI 11.3 to 17.9). Among patients with surgery, definitive resection was associated with a median OS of 51 months (95% CI 11.7 to 55.3) compared with 11 months (95% CI 4.1 to 23.6) for those with unresectable disease (p = 0.003). Conclusions Even without distant metastases, locally advanced or lymph node-positive GBCA is associated with poor outcomes. Definitive resection was possible in a subset of patients selected for surgery after a favorable response to chemotherapy and was associated with long-term survival. We recommend surgical re-evaluation after chemotherapy to select potential operative candidates.

BACKGROUND Irreversible electroporation (IRE) has emerged as a novel, safe ablative therapy for peri-vascular lesions. However, there remains a paucity of data on long-term outcomes. METHODS We identified patients who underwent open IRE (1/2011-6/2015) for primary and secondary hepatic malignancies. Local ablation-zone recurrence (LR) was determined by cross-sectional imaging. Cumulative incidence (CumI) of LR was calculated and a competing risks regression assessed factors associated with LR. RESULTS Forty patients had 77 lesions treated. The majority of lesions were of colorectal origin (74%). Median tumor size was 1.3 cm (range 0.5-6). Most patients (86%) had prior systemic therapy and 29% received systemic therapy following IRE. With a median follow-up of 25.7 months (range 4.5-58.8 months), 10 lesions in 9 patients recurred locally (CumI: 13.4%, 95%CI: 7.8-22.2%). Median estimated time to LR was not reached and no LR occurred after 19 months. Factors significantly associated with LR included ablation zone size (HR 1.58; 95%CI 1.12-2.23; P = 0.0093) and body mass index (HR 1.21 95%CI 1.10-1.34; P = 0.0001). CONCLUSION IRE LR rates were low after the treatment of well selected, small tumors. This technique is useful for lesions in anatomic locations precluding resection or thermal ablation.

Background The first International conference on Minimally Invasive Pancreas Resection was arranged in conjunction with the annual meeting of the International Hepato-Pancreato-Biliary Association (IHPBA), in Sao Paulo, Brazil on April 19th 2016. The presented evidence and outcomes resulting from the session for minimally invasive distal pancreatectomy (MIDP) is summarized and addressed perioperative outcome, the outcome for cancer and patient selection for the procedure. Methods A literature search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to compare MIDP and open distal pancreatectomy. Patient selection was discussed based on plenary talks, panel discussions and a worldwide survey on MIDP. Results Of 582 studies, 52 (40 observational and 12 case-matched) were included in the assessment for outcome for LDP (n = 5023) vs. ODP (n = 16,306) whereas 16 observational comparative studies were identified for cancer outcome. No randomized trials were identified. MIDP resulted in similar outcome to ODP with a tendency for lower blood loss and shorter hospital stay in the MIDP group. Discussion Available evidence for comparison of MIDP to ODP is weak, although the number of studies is high. Observed outcomes of MIDP are promising. In the absence of randomized control trials, an international registry should be established.

Background In 2005, the International Study Group of Pancreatic Fistula developed a definition and grading of postoperative pancreatic fistula that has been accepted universally. Eleven years later, because postoperative pancreatic fistula remains one of the most relevant and harmful complications of pancreatic operation, the International Study Group of Pancreatic Fistula classification has become the gold standard in defining postoperative pancreatic fistula in clinical practice. The aim of the present report is to verify the value of the International Study Group of Pancreatic Fistula definition and grading of postoperative pancreatic fistula and to update the International Study Group of Pancreatic Fistula classification in light of recent evidence that has emerged, as well as to address the lingering controversies about the original definition and grading of postoperative pancreatic fistula. Methods The International Study Group of Pancreatic Fistula reconvened as the International Study Group in Pancreatic Surgery in order to perform a review of the recent literature and consequently to update and revise the grading system of postoperative pancreatic fistula. Results Based on the literature since 2005 investigating the validity and clinical use of the original International Study Group of Pancreatic Fistula classification, a clinically relevant postoperative pancreatic fistula is now redefined as a drain output of any measurable volume of fluid with an amylase level >3 times the upper limit of institutional normal serum amylase activity, associated with a clinically relevant development/condition related directly to the postoperative pancreatic fistula. Consequently, the former “grade A postoperative pancreatic fistula” is now redefined and called a “biochemical leak,” because it has no clinical importance and is no longer referred to a true pancreatic fistula. Postoperative pancreatic fistula grades B and C are confirmed but defined more strictly. In particular, grade B requires a change in the postoperative management; drains are either left in place >3 weeks or repositioned through endoscopic or percutaneous procedures. Grade C postoperative pancreatic fistula refers to those postoperative pancreatic fistula that require reoperation or lead to single or multiple organ failure and/or mortality attributable to the pancreatic fistula. Conclusion This new definition and grading system of postoperative pancreatic fistula should lead to a more universally consistent evaluation of operative outcomes after pancreatic operation and will allow for a better comparison of techniques used to mitigate the rate and clinical impact of a pancreatic fistula. Use of this updated classification will also allow for more precise comparisons of surgical quality between surgeons and units who perform pancreatic surgery.

Emerging data suggest that not all grade 3 (G3) pancreatic neuroendocrine neoplasms (panNENs) behave the same; tumor differentiation may predict outcome.Patients with G3 panNENs treated at our institution between 1999 and 2014 were identified. Demographics, response to therapy, and overall survival were determined.Forty-five patients were identified, 16 with G3 well differentiated pancreatic neuroendocrine tumors (WD-panNETs) and 29 with poorly differentiated neuroendocrine carcinomas (PDNEC). Median overall survival in G3 WD-panNET patients was 52.2 months (95% confidence interval, 19.3-86.9 months) compared with 10.1 months (95% confidence interval, 6.9-12.4 months) in PDNEC patients (P = 0.0009). Response rate to platinum agents was 10% in G3 WD-panNETs and 37% in PDNEC. Response rate to alkylating agents was 50% in G3 WD-panNETs and 50% in PDNEC.Both G3 WD-panNETs and PDNEC responded to platinum and alkylating agents. Overall survival was significantly greater in G3 WD-panNETs compared with PDNEC. These findings challenge current classification and suggest that G3 panNENs should be classified by morphology.