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While angiotensin-converting enzyme (ACE) regulates blood pressure by producing angiotensin II as part of the renin-angiotensin system, we recently reported that elevated ACE in neutrophils promotes an effective immune response and increases resistance to infection. Here, we investigate if such neutrophils protect against renal injury in immune complex (IC)-mediated crescentic glomerulonephritis (GN) through complement. Nephrotoxic serum nephritis (NTN) was induced in wild-type and NeuACE mice that overexpress ACE in neutrophils. Glomerular injury of NTN in NeuACE mice was attenuated with much less proteinuria, milder histological injury, and reduced IC deposits, but presented with more glomerular neutrophils in the early stage of the disease. There were no significant defects in T and B cell functions in NeuACE mice. NeuACE neutrophils exhibited enhanced IC uptake with elevated surface expression of FcγRII/III and complement receptor CR1/2. IC uptake in neutrophils was enhanced by NeuACE serum containing elevated complement C3b. Given no significant complement activation by ACE, this suggests that neutrophil ACE indirectly preactivates C3 and that the C3b-CR1/2 axis and elevated FcγRII/III play a central role in IC elimination by neutrophils, resulting in reduced glomerular injury. The present study identified a novel renoprotective role of ACE in glomerulonephritis; elevated neutrophilic ACE promotes elimination of locally formed ICs in glomeruli via C3b-CR1/2 and FcγRII/III, ameliorating glomerular injury.

The specific fatty acid (FA) profile of colostrum may indicate a biological requirement for neonatal calves. The objective of this study was to characterize the FA profile and yields in colostrum, transition milk, and mature milk in primiparous (PP) and multiparous (MP) cows. Colostrum was milked from 10 PP and 10 MP Holstein cows fed the same pre- and postpartum rations. Milkings (M) 2 to 5 and 12 were respectively termed transition and mature milk. Overall, short-chain FA (C4:0 and C6:0) were 61 and 50% lower in colostrum than mature milk, respectively. A parity by milking interaction was also present, with higher C4:0 for PP cows at M2 and for MP cows at M12. Additionally, higher concentrations of C6:0 were present for PP cows at M2 through M4 and for MP cows at M12. Palmitic (C16:0) and myristic (C14:0) acids were 38% and 19% higher in colostrum than mature milk, respectively. However, total saturated FA remained relatively stable. Branched-chain FA were 13% lower in colostrum than mature milk and higher in PP than MP cows throughout the milking period. The proportion of trans-monounsaturated FA (MUFA) was 72% higher in PP cows throughout the milking period, as well as 13% lower in colostrum than mature milk. In contrast, cis-MUFA and total MUFA were not affected by milking nor parity. Linoleic acid (LA) was 25% higher in colostrum than transition and mature milks, but α-linolenic acid (ALA) did not differ. Consequently, the ratio of LA to ALA was 29% higher in colostrum than mature milk and 33% higher in MP cows. Linoleic acid was also 15% higher in MP cows, whereas ALA was 15% higher in PP cows. Conjugated linoleic acid (CLA, cis-9,trans-11) was 2.7-fold higher in PP cows, and no differences between colostrum and mature milk were detected. Overall, polyunsaturated FA (PUFA) from the n-6 and n-3 series were over 40% higher in colostrum compared with transition and mature milk. Milking by parity interactions were present for arachidonic acid (ARA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), and total n-3 PUFA, translating to higher proportions in PP cows in M1 to M3, whereas proportions remained relatively stable throughout the milking period in MP cows. Despite increasing milk yields throughout the subsequent milkings, higher yields of EPA, ARA, DPA, and DHA were present in colostrum than in mature milk. Greater proportions and yields of n-3 and n-6 FA in colostrum may translate to specific requirements for newborn calves. Differences were also observed between PP and MP cows and may reflect different nutrient requirements and partitioning.

This essay examines how maps created by Latina/o youth created “ephemeral forums,” improvised ad hoc spaces that served as music venues in 1990s South Los Angeles. The maps included on “Rock en Español” event flyers demonstrate how Latinx youth envisioned Los Angeles and proclaimed their sense of place in the metropolis at a moment of social and demographic transformation. These maps help us understand how they and other Californians of color create and claim belonging,both past and present.

How do marginalized ethnic communities assert their presence in the American urban space? This article examines maps and location descriptions found in ‘Rock Angelino’ concert flyers, lyrics of songs, and spoken word multimedia pieces as examples of ‘mapping from below’ practices from the 1990s to the near present, which Latinxs have used to place themselves in the historical geography and cultural imaginary of Los Angeles. While people of Latin American descent have been part of Los Angeles since its founding, their presence has often been neglected and diminished in the maps created by government agencies, and in more recent times, by gentrifying real estate enterprises that inaccurately portray the past and present of Los Angeles as a White space with few selective geographical locations of communities of colour. By employing critical geography and cultural history methodologies, this piece demonstrates how Latinxs have been cartographers of their own communities. Most significantly how Latinxs employed their words and sounds as mapping tools with which to chart, examine, narrate and make visible the rich layered histories of Latinxs and communities of colour in Southern California.

Introduction Staphylococcus aureus is part of the human flora, present in the skin and mucous membranes but can become pathogenic, causing a wide spectrum of infections that were initially treated with penicillin. However, were observed some strains with resistance to this antibiotic and, therefore was developed a new antibiotic, the methicillin. After its introduction, arose the first S. aureus with resistance to methicillin (MRSA) due to the presence of a gene known as mecA that encodes an altered penicillin binding protein (PBP2a). In Europe, it is estimated that MRSA are associated to 44% of hospital acquired infections and its mortality rate is around 20%. Objectives Prevalence of MRSA strains in different types of infection in Coimbra district. Methodology Were analysed a total of 539 isolates of S. aureus previously characterized to the antibiotic susceptibility profile in the Hospital and University Center of Coimbra. Through the minimum inhibitory concentration (MIC) of oxacillin we classified our strains into MRSA and S. aureus methicillin-sensitive (MSSA); simultaneously, the mecA gene was detected by Polymerase Chain Reaction (PCR). Results Of the 539 isolates, 49% were considered MRSA and 51% MSSA. All MRSA isolates express the mecA gene, but from the total of 276 MSSA, 191 show this gene but do not express it. MRSA isolates were mostly from respiratory tract samples (48%) and blood cultures (21%) while MSSA were isolated in skin and soft tissue samples (35%). Conclusion MRSA are considered one of the primary pathogens for the development of pneumonia and septicaemia due to its highly virulent potential and the increasing expression of genetic determinants of antimicrobial resistance. Therefore, infections caused by MRSA continue with highly representability in the clinical context and their dissemination is a public health problem.

BACKGROUND: In 2017, the WHO updated their 2010 classification of pancreatic neuroendocrine tumors, introducing a well-differentiated, highly proliferative grade 3 tumor, distinct from neuroendocrine carcinomas. The aim of this study was to investigate the clinical significance of this update in a large cohort of resected tumors.METHODS: Using a multicenter, international dataset of patients with pancreatic neuroendocrine lesions, patients were classified both according to the WHO 2010 and 2017 schema. Multivariable survival analyses were performed, and the models were evaluated for discrimination ability and goodness of fit.RESULTS: Excluding patients with a known germline MEN1 mutation and incomplete data, 544 patients were analyzed. The performance of the WHO 2010 and 2017 models was similar, however surgically resected grade 3 tumors behaved very similarly to neuroendocrine carcinomas.CONCLUSION: The addition of a grade 3 NET classification may be of limited utility in surgically resected patients, as these lesions have similar postoperative survival compared to carcinomas. While the addition may allow for a more granular evaluation of novel treatment strategies, surgical intervention for high grade tumors should be considered judiciously.

Female Mexican fruit flies, Anastrepha ludens (Loew), have the capacity to produce more than 1,000 eggs over their lifetime, but fertility of the eggs will depend on the female's capacity to store semen or to replenish semen through remating or both. The two parameters are interrelated in that sexual receptivity depends to a large degree on insemination status. In this controlled study, we measured sperm depletion in singly mated females with continuous access to oviposition substrates by using a squash technique. The spermathecae were sequentially emptied of sperm over the 3 weeks following copulation. Under laboratory conditions, sperm was always found in the ventral receptacle up to 4 weeks following copulation, but was empty in almost all females by the fifth week. These results mirrored previous measurements of egg fertility in singly mated females, which declines at 26–40 d postcopulation.

Deforestation of tropical forests has contributed to the formation of fragmented landscapes, surrounded mainly by a matrix of secondary forests, pastures and agriculture. In this study we evaluated the fragment-area effects on the density, diversity and composition of the soil seed bank. Fragments of primary forest of different sizes (1, 10 and 100 ha) and continuous primary forests were sampled in a region of terra firme forest in Central Amazonia. We collected 180 soil samples (45 samples per treatment), and monitored seedling emergence from the soil seed bank in a greenhouse for seven months. Density of emerged seedlings, floristic composition, richness and diversity of species were compared among treatments with Kruskal-Wallis non-parametric test, Mann-Whitney test, Fisher's Alpha diversity index and Non-metric multidimensional scaling (NMDS). Seedling density was inversely proportional to the size of the fragment, being higher in fragments of 1 ha, 10 ha, and lower in the primary forest and fragments of 100 ha. Diversity was higher in the fragments when compared to the primary forests. Melastomataceae was the most abundant family in all treatments. Species composition changed along the disturbance gradient, and is dominated, in the smaller fragments by species that are indicators of degraded environments. Results suggested that the area of the forest fragments affects the size and composition of the soil seed bank, and can significantly influence the potential resilience and regeneration of these sites in the event of natural or anthropic disturbance.

Clinical outcomes of octogenarians undergoing hepatectomy for colorectal liver metastases (CRLM) are poorly characterized. The current study evaluated operative morbidity, mortality and survival outcomes among a contemporary cohort of octogenarians.Patients undergoing their first hepatectomy for CRLM were identified from institutional databases and those ≥80 years old (y) were matched 1:1 to a group of patients80 y. Data pertaining to surgical morbidity/mortality and survival were compared using standard statistical methods.From 2002 to 2012, 1391 hepatectomies were performed for CRLM, 55 (4%) in patients ≥80 y. Major complications occurred twice as frequently among patients ≥80 y [10 (19%) ≥80 y versus 5 (9%)80 y, (p = 0.270)]. No matched patient80 y. died within 90 d of operation, whereas, 4 (7%) patients ≥80 y did, p = 0.125. Median follow-up was significantly longer for the80 y group [44 (1-146) versus. 23 (0-102) mths, p = 0.006]. Probability of disease recurrence was not different between groups (p = 0.123) nor was the cumulative incidence of death from disease (p = 0.371). However, patients ≥80 y had significantly higher incidence of non-cancer related death (p = 0.012).Hepatectomy for CRLM among well-selected octogenarians is reasonable with cancer related survival outcomes similar to those observed in younger patients. However, it is associated with clinically significant morbidity/mortality and continued efforts directed at optimizing perioperative care are necessary to improve early outcomes among octogenarians.

The increasing availability of automated milk dispensers on dairy farms facilitates ad libitum milk supply but weaning calves from high milk allowances is challenging. This study evaluated effects of gradual weaning methods on starter intake, growth, selected blood parameters and weaning distress in ad libitum fed dairy calves during weaning and early post-weaning periods. Thirty-six male Holstein (n = 30) or crossbred (n = 6) calves were individually housed from days 2 to 14 of age and had ad libitum access to milk replacer (MR) from teat buckets. From days 15 to 84 of age, calves were grouped and had ad libitum access to MR, starter, straw and water from automated feeders. At day 35, calves were blocked (age and breed), and randomly assigned to a weaning method: (1) linear fixed (LIN), MR supply was stepped down to 6 l/day on day 36, and linearly reduced between days 36 to 63 from 6 to 2 l/day. (2) Step-down (STEP), MR supply was stepped down to 6 l/day from days 36 to 48, 4 l/day from days 49 to 56 and 2 l/day from days 57 to 63. (3) Dynamic (DYN), at day 36, MR supply was reduced for each individual calf to 75% of the average voluntary consumption between day 29 and 35, then maintained for 9 days, reduced to 50% for 10 days, and to 25% for 9 days. The DYN calves received more MR during weaning than LIN calves, whereas STEP calves had intermediate MR intake. Starter intake was not affected by weaning method. The DYN calves (1.33±0.08 kg/day) grew faster and were heavier than STEP calves (1.10±0.08 kg/day) during post-weaning period, whereas no difference was observed between LIN calves (1.23±0.08 kg/day) and others. At days 70 and 84, concentrations of β-hydroxybutyric acid were higher in LIN calves compared to STEP and DYN calves. Hair cortisol concentrations were not affected by weaning method. During the gradual weaning process CP intake seemed to recovered earlier than metabolizable energy (ME) intake in all treatments, suggesting that ME rather than CP could be the first limiting factor for growth during weaning. These results highlight the post-weaning benefits of DYN and LIN weaning methods when compared with more abrupt step-down strategies.

Meat quality, as defined by its colour stability is the main sensory attribute of lamb meat that drives consumer preference and purchase decision. The ‘bright red’ colour in meat, perceived by consumers as an indicator of freshness and superior product quality, can be further enhanced by highly oxidizing packaging methods. Overtime, these packaging methods also accelerate the deterioration of colour, flavour and texture. To delay that, meat processors and retailers have adopted the use of antioxidants into animal diets. Based on the work described in this thesis, under similar experimental conditions, it was found that vitamin E is more effective than plant extracts at maintaining the colour stability of lamb meat.

Various segments of Variscan crust are currently exposed in Iberia in response to successive tectonic events during the Variscan orogeny itself and subsequent extensional and compressive events during the Alpine cycle, all accompanied by surface erosion, and collectively contributing to their exhumation. We review the main characteristics and geodynamic contexts of the metamorphic complexes developed in Iberia during the Variscan cycle, which include: (i) LP-HT complexes associated to the Cambrian-Early Ordovician rift stage; (ii) HP-LT complexes associated to subduction; and (iii) syn-to-post-collisional, MP and LP/HT complexes from the hinterland to the foreland fold-and thrust belts. All the above contexts are illustrated with case studies. Finally, a review of Variscan metamorphism in the Pyrenees and Catalan Coastal Ranges, located far away from the Rheic suture is also presented. published

When supplementing lamb diets with vitamin E, an equivalence factor of 1.36 is used to discriminate between RRR-α-tocopheryl acetate and all-rac-α-tocopheryl acetate. However, more recent studies suggest a need for new equivalence factors for livestock animals. The current study aimed to determine the effect of RRR- and all-rac-α-tocopheryl acetate supplementation on α-tocopherol deposition in lamb tissues. A total of 108 Rasa Aragonesa breed lambs were fed increasing amounts of all-rac-α-tocopheryl acetate (0.25, 0.5, 1.0 and 2.0 g/kg compound feed) or RRR-α-tocopheryl acetate (0.125, 0.25, 0.5 and 1.0 g/kg compound feed) by adding them to a basal diet that contained 0.025 g/kg feed of all-rac-α-tocopheryl acetate as part of the standard vitamin and mineral mixture. The diets were fed for the last 14 days before slaughtering at 25.8±1.67 kg BW. Within 20 min after slaughter samples of muscle, heart, liver, brain and spleen were frozen at -20°C until α-tocopherol analysis. Increased supplementation of either vitamin E sources led to a significant increase (P0.001) in α-tocopherol concentration in all tissues studied. The tissue with the highest α-tocopherol concentration was the liver followed by spleen, heart and muscle. At similar supplementation levels (0.25, 0.50 and 1.0 g/kg compound feed), α-tocopherol content in the selected tissues was not affected by α-tocopherol source. However, the ratios between RRR- and all-rac-α-tocopheryl acetate increased with the increasing α-tocopherol supplementation (at 0.25 and 1.0 g/kg compound feed), from 1.06 to 1.16 in muscle, 1.07 to 1.15 in heart, 0.91 to 0.94 in liver and 0.98 to 1.10 in spleen. The highest relative proportion of Ʃ2S (sum of SSS-, SSR-, SRS- and SRR-α-tocopherol)-configured stereoisomers was found in the liver of lambs supplemented with all-rac-α-tocopheryl acetate accounting for up to 35 to 39% of the total α-tocopherol retained, whereas the proportion of Ʃ2S-configured stereoisomers in the other tissues accounted for14%. Increasing all-rac-α-tocopheryl acetate supplementation was also found to affect the 2R-configured stereoisomer profile in muscle, heart and spleen with increasing proportions of RRS-, RSR- and RSS- at the cost of RRR-α-tocopherol. In all tissues, the relative proportion of all non-RRR-stereoisomers in lambs receiving RRR-α-tocopheryl acetate was lower than RRR-α-tocopherol. These results confirm that the relative bioavailability of RRR- and all-rac-α-tocopheryl acetate is dose- and tissue-dependent and that a single ratio to discriminate the two sources cannot be used.

The aim of this study was to assess splenic volume and to correlate unidimensional measurements with reference volumetric changes in chemotherapy-treated patients with colorectal cancer (CRC) liver metastases.Forty consecutive patients were selected from the cohort of a previously reported study of chemotherapy-related morbidity following major hepatectomy for CRC liver metastases. Patients were treated for 6 months prior to resection, with imaging performed at baseline and after 6 months of chemotherapy. Three unidimensional spleen measurements were recorded-width, thickness, and height (W, T, and H). Reference splenic volume was measured at baseline and after chemotherapy. The best unidimensional splenic measurement was determined by regression analysis. The 95% CI for the predicted values and R (2) values was calculated for each regression. The percentage of volume increase at 6 months was calculated.W and H showed the highest correlation with splenic volume prior to and following chemotherapy (R (2) = 0.65-0.74, p 0.001), while T showed a low correlation (R (2) = 0.11 and 0.18, p 0.05). The mean reference splenic volume increased after 6 months of chemotherapy compared to baseline (326 vs. 278 mL). Splenic volume changes showed the highest correlation with changes in W (R (2) = 0.56, p 0.001), then H (R (2) = 0.40, p 0.001), but were not significantly correlated with changes in T (R (2) = 0.01, p = 0.055).Our results show the potential utility of measuring changes in splenic width to predict clinically significant changes in splenic volume in chemotherapy-treated patients with CRC liver metastases.

In patients with colorectal cancer liver metastases (CRCLM), chemotherapy-induced hepatic injury is associated with increased splenic volume, thrombocytopenia, and decreased long-term survival. The current study investigates the relationship between change in splenic volume after preoperative chemotherapy and development of postoperative complications.The study group consisted of 80 patients who underwent resection of CRCLM; half received neoadjuvant chemotherapy for 6 months before resection (n = 40) and the other half did not (n = 40). The study group was compared with two control groups: a normal group composed of patients undergoing cholecystectomy for benign disease (n = 40) and a group of untreated, nonmetastatic colorectal cancer (CRC) patients (n = 40). Splenic volume was measured by CT/MRI volumetry. In the study group, the nontumoral liver was graded for steatosis and sinusoidal injury; operative and outcomes characteristics were also analyzed.Before chemotherapy, CRCLM patients had normalized spleen volumes of 3.2 ± 1.1 mL/kg, significantly higher than normal (2.5 ± 0.8 mL/kg; p0.001) and nonmetastatic CRC (2.6 ± 1.3 mL/kg; p0.05) patients, with higher splenic volume after 6 months of chemotherapy (4.2 ± 1.7 mL/kg; p0.01). After chemotherapy, splenic volume increase was associated with any perioperative complication (p0.01) and major complications (p0.05). Patients with ≥39% splenic volume increase (maximal chi-square test) were significantly more likely to have major complications (p0.01). Spleen volume changes were not correlated with change in platelet count (R(2) = 0.03; p = 0.301).In patients with CRCLM, the presence of liver metastases and chemotherapy are associated with higher splenic volume. Percent splenic volume increase after 6 months of chemotherapy can aid preoperative risk stratification, as it was an independent predictor of major postoperative complications.

To date, hepatic artery infusion (HAI) chemotherapy has primarily been investigated in the setting of colorectal cancer liver metastases (CRLM). Few studies have been conducted in North America regarding HAI chemotherapy for primary liver cancers (PLC) or noncolorectal liver metastases (non-CRLM). Despite decades of evaluation, controversy surrounding the use of HAI chemotherapy still exists. In this article the methods of HAI chemotherapy delivery, technical aspects of catheter and pump insertion, and specific complications of HAI chemotherapy are discussed. Outcomes of clinical trials and reviews of HAI chemotherapy in the setting of CRLM, PLC, and non-CRLM are evaluated.

Supra-nutritional vitamin E supplementation is a commonly used approach to delay lipid oxidation and colour deterioration in lamb and beef meat marketed under modified atmosphere packaging. However, these applications lack a precise calibration of dose for the desired effect and, in addition, limited information is available regarding the use of natural vitamin E for this purpose.Three hundred and sixty Rasa Aragonesa lambs were fed diets supplemented with all-rac-α-tocopheryl acetate (250, 500, 1000 and 2000 mg kgThe quantification of these effects demonstrated that the biological activity value of 1.36 used to distinguish both vitamin E sources is not appropriate for meat quality enhancing properties. © 2017 Society of Chemical Industry.

The pericytic (perivascular myoid cell) family of tumors is a distinctive group of mesenchymal neoplasms encountered in superficial sites and only rarely seen in viscera. The pericytic family subtends a spectrum of lesions, namely, glomus tumors and variants; myopericytoma, including myofibroma; and angioleiomyoma. In light of the contemporary classification of pericytic lesions, we identified and reviewed 17 cases of renal pericytic tumors from the files of 6 referral centers. These tumors presented over an age range of 17 to 76 years (mean 46.7, median 53), with essentially equal male-female ratio. History of hypertension (available in 11 patients) was noted in 7 (64%), which persisted even after surgical resection, including in 2 younger patients (17 and 30 years). The tumors (1.7-11.0 cm) included glomus tumors (n=11); glomangiomyoma (n=1); glomus tumor with atypical features (n=1); and angioleiomyoma (n=1), as well as tumors showing features overlapping pericytic tumor subtypes (n=3). The histomorphology observed in these renal examples closely resembled that of their soft tissue counterparts, a subset with symplastic changes and atypical features, and pericytic immunophenotype. Despite large size and deep site, no progression was identified during a median of 7 months follow-up (1-62 months). In context of prior reported experience, our series identifies a wide morphologic spectrum, including lesions presenting composite morphologies. Taken with the experience of others, our series further corroborates that malignant behavior is rare, and that criteria associated with aggression among soft tissue pericytic tumors may not be predictive for those in the kidney.

Purpose To investigate whether perioperative hepatic arterial infusion pump chemotherapy (HAI) was associated with overall survival (OS) in patients who had a complete resection of colorectal liver metastases (CLM). Methods Patients who underwent a complete resection of CLM between 1992 and 2012 were included from a single-center prospectively maintained database. All patients who received HAI also received perioperative systemic chemotherapy. Propensity score analysis was used to match patients for seven known prognostic factors. Results A total of 2,368 consecutive patients underwent a complete resection of CLM, with a median follow-up of 55 months. The median OS for patients with HAI (n = 785) was 67 months versus 44 months without HAI (n = 1,583; P < .001), despite more advanced disease in the HAI group. OS at 10 years was 38.0% versus 23.8% without HAI. For patients who received modern systemic chemotherapy (n = 1,442), the median OS was 67 months with HAI and 47 months without HAI ( P < .001). The hazard ratio adjusted by propensity score demonstrated longer OS with HAI: 0.67 (95% CI, 0.59 to 0.76; P < .001). A pronounced difference in median OS was found for patients with node-negative colorectal cancer (129 months with HAI v 51 months without; P < .001) and a low clinical risk score of 0 to 2 points (89 months with HAI v 53 months without; P < .001). Conclusion Patients who received HAI had a median OS of approximately 2 years longer than patients without HAI. The strong association was independent of the use of modern systemic chemotherapy and remained in propensity score analysis. Patients with node-negative primary tumors or a low clinical risk score seemed to benefit most from HAI.

Fistula Risk Score (FRS) is a previously developed tool to assess the risk of clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreatoduodenectomy (PD).Prospectively collected databases from 4 university affiliated and non-affiliated HPB centers in United States and Canada were used. The influence of individual baseline characteristics, FRS and FRS group on CR-POPF was assessed in univariate and multivariate analyses. FRS calculator performance was assessed using a C-statistic.444 patients were identified. Pathology, soft pancreas texture and pancreatic duct size were associated with CR-POPF rates (p 0.001 for each); EBL was not (p = 0.067). The negligible risk group consisted of 50 (11.3%) patients, low risk of 118 (26.6%), moderate 234 (52.7%) and high risk group of 42 (9.5%) patients. The overall rate of CR-POPF was 20%. Of the patients in the negligible risk group, 2% developed CR-POPF, 13.6% of the low risk, 23.1% moderate and 42.9% in the high risk group (p 0.001). Overall C-statistic was 0.719.FRS is robust and able to stratify the risk of developing CR-POPF following PD in diverse North American academic and non-academic institutions. The FRS should be used in research and to guide clinical management of patients post PD in these institutions.

Worldwide, colorectal cancer (CRC) is one of the most common malignancies. At presentation, metastatic spread is observed in approximately 20 % of patients with a further 50 % developing metastases during their disease course. In patients who develop metastases, 80 % have some form of liver involvement. The only treatment for patients with isolated colorectal cancer liver metastases (CRLM) associated with potential long-term survival and cure is surgery. Unfortunately, most patients (75–80 %) have disease that is not amenable to surgical intervention. However, recent advances in all areas of the management of CRLM have resulted in more numerous treatment options for this population of patients. Developments in diagnosis, medical therapy (chemotherapy, targeted therapy), nonsurgical locoregional therapy (ablation, embolization, hepatic artery infusion chemotherapy), and surgical therapy have expanded the treatment armamentarium for patients with CRLM and subsequently increased the complexity of management. Many newer therapies/treatment strategies have proven effective; however, there is debate regarding the ideal clinical implementation. In order to optimize clinical outcomes in patients with CRLM, awareness of current and emerging therapies and treatment strategies is essential.

Resection of colorectal liver metastases (CRLM) is associated with improved survival; however, the impact of time to resection on survival is unknown. The current multi-institutional study sought to evaluate the influence of time from diagnosis (Dx) to resection (Rx) on survival outcomes among patients with resectable, metachronous CRLM and to compare practice patterns across hospitals.Medical records of patients with ≤4 metachronous CRLM treated with surgery were reviewed and analyzed retrospectively. Time from Dx to Rx was analyzed as a continuous variable and also dichotomized into 2 groups (group 1: Dx to Rx3 months and group 2: Dx to Rx ≥3 months) for additional analysis. Survival time distributions after resection were estimated using the Kaplan-Meier method. Between-group univariate comparisons were based on the log-rank test and multivariable analysis was done using Cox proportional hazards model.From 2000 to 2010, six hundred and twenty-six patients were identified. Type of initial referral (p0.0001) and use of neoadjuvant (p = 0.04) and/or adjuvant (p0.0001) chemotherapy were significantly different among hospitals. Patients treated with neoadjuvant chemotherapy (n = 108) and those with unresectable disease at laparotomy (n = 5) were excluded from final evaluation. Median overall survival and recurrence-free survival were 74 months (range 63.8 to 84.2 months) and 29 months (range 23.9 to 34.1 months), respectively. For the entire cohort, longer time from Dx to Rx was independently associated with shorter overall survival (hazard ratio = 1.12; 95% CI, 1.06-1.18; p0.0001), but not recurrence-free survival. Median overall survival for group 1 was 76 months (range 62.0 to 89.2 months) vs 58 months (range 34.3 to 81.7 months) in group 2 (p = 0.10). Among patients with available data pertaining to adjuvant chemotherapy (N = 457; 318 treated and 139 untreated), overall survival (87 months [range 71.2 to 102.8 months] vs 48 months [range 25.3 to 70.7 months]; p0.0001), and recurrence-free survival (33 months [range 25.3 to 40.7 months] vs 22 months [range 14.5 to 29.5 months]; p = 0.05) were improved significantly.In select patients undergoing initial resection for CRLM, longer time from Dx to Rx is independently associated with worse overall survival. In addition, despite uniform disease characteristics, practice patterns related to definitely resectable CRLM vary significantly across hospitals.

The impact of margin width on overall survival (OS) in the context of other prognostic factors after resection for colorectal liver metastases is unclear. We evaluated the relationship between resection margin and OS utilizing high-resolution histologic distance measurements.A single-institution prospectively maintained database was queried for all patients who underwent an initial complete resection of colorectal liver metastases between 1992 and 2012. R1 resection was defined as tumor cells at the resection margin (0 mm). R0 resection was further divided into 3 groups: 0.1 to 0.9 mm, 1 to 9 mm, and 10 mm or greater.A total of 4915 liver resections were performed at Memorial Sloan Kettering Cancer Center between 1992 and 2012, from which 2368 patients were included in the current study. Half of the patients presented with synchronous disease, 43% had solitary metastasis, and the median tumor size was 3.4 cm. With a median follow-up for survivors of 55 months, the median OS of the R1, 0.1 to 0.9 mm, 1 to 9 mm, and 10 mm or more groups was 32, 40, 53, and 56 months, respectively (P0.001). Compared with R1 resection, all margin widths, including submillimeter margins correlated with prolonged OS (P0.05). The association between the margin width and OS remained significant when adjusted for all other clinicopathologic prognostic factors.Resection margin width is independently associated with OS. Wide margins should be attempted whenever possible. However, resection should not be precluded if narrow margins are anticipated, as submillimeter margin clearance is associated with improved survival. The prolonged OS observed with submillimeter margins is likely a microscopic surrogate for the biologic behavior of a tumor rather than the result of surgical technique.

The aim of this study is to determine the prevalence of diabetes mellitus (DM) in patients with intraductal papillary mucinous neoplasm of the pancreas (IPMN) and compare rates of new/progressive DM between IPMN patients undergoing pancreatectomy versus observation. Patients diagnosed with IPMN were identified from institutional databases, divided into two groups based on treatment type, pancreatectomy versus clinical observation, and subsequently evaluated. Standard demographic and clinicopathologic variables, fasting glucose, diabetic status, and pancreatic volume data, were obtained and compared between groups. One hundred thirty-four IPMN patients were identified; 103 (77 %) underwent pancreatectomy and 31 (23 %) were observed. Baseline DM rate was 18 % (24/134). This was not different between groups [17 % (17/103) resected vs. 23 % (7/31) observed, p = 0.51]. Median follow-up was 53 months and new/progressive DM occurred in 37 (28 %) patients with no difference between groups [29 (28 %) resected vs. 8 (26 %) observed, p = 0.74]. Among resected patients, degree of dysplasia was associated with increase risk of new/progressive DM [moderate dysplasia OR 5.76 (1.24–26.79) and severe dysplasia OR 9.43 (1.54–57.74), p = 0.04], while procedure type and remnant volume were not. The incidence and prevalence of DM among patients with IPMN was high and did not differ between resected and observed groups. Degree of dysplasia, not the amount of resected pancreas, was associated with increased risk of DM, suggesting that the presence or development of DM may be a marker of malignant progression. Confirmatory studies are required.

Purpose To evaluate the use of locoregional therapy in patients with hepatocellular carcinoma (HCC) with and without extrahepatic disease (EHD). Materials and Methods Patients who underwent locoregional therapy for HCC were identified from institutional databases. Clinicopathologic and treatment characteristics were compared between patients with and without EHD. Survival and progression were assessed using the Kaplan-Meier method, and multivariate analysis was completed. Results Of 224 patients, 39 (17%) had radiologic evidence of EHD. Patients without EHD were older than patients with EHD (68.8 y ± 10.1 vs 65.0 y ± 11.7, P = .04); underlying liver disease/function and tumor characteristics were not different. Type of locoregional therapy (hepatic artery embolization vs drug-eluting bead transarterial chemoembolization, P = .12; radiofrequency ablation + embolization, P = .07) was similar. Progression occurred in 75% (169/224) of patients. Progression-free survival (PFS) did not differ between the 2 groups (13 [10.3–15.7] mo EHD vs18 [14.6–21.4] mo no EHD, P=.13). Overall survival (OS) was 13 (4.1–21.9) months and 25 (20.4–29.6) months in the EHD and no EHD groups, respectively ( P = .02). On multivariate analysis, systemic therapy after locoregional treatment was the only variable independently associated with PFS (hazard ratio [HR] 0.70 [0.49–1.00], P = .04); EHD (HR 1.60 [1.02–2.50], P = .04) and tumor size (HR 1.77 [1.21–2.58], P = .003) were independently associated with worse OS. Conclusions Patients with HCC and limited EHD treated with locoregional therapy had worse OS than patients without EHD; PFS was not different. Use of systemic therapy after locoregional therapy was independently associated with improved PFS in this cohort. Further prospective studies of locoregional, systemic, and combination therapies are necessary to improve outcome in these high-risk patients.