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Compared to Sendai-positive patients, the Sendai negative group were younger (67 years vs. 70 years; P=0.039), mostly female (65.7% vs. 47.8%; P < 0.001), had higher rates of family history of pancreatic cancer (23.2 % vs. 9.8%%; P < 0.001), and lower rates of diabetes (14.3% vs. 32.2%; P=0.049). Among Sendai-negative patients, 12 (12.1%) had IPMN with high-grade dysplasia and only one patient (1.0%) had invasive carcinoma which was significantly lower compared to Sendai-positive patients (high-grade: 26.0%; invasive carcinoma: 28.7%; P < 0.001). The 5-year estimated overall survival was 84% in Sendai-negative patients with low-risk IPMN, which was comparable to 85.7% in Sendai-positive patients with high-risk IPMN (P=0.84; figure). [Extracted from the article]

B Presenter: b A. Floortje van Oosten MD | Johns Hopkins University School of Medicine B Background: b Improved systemic and radiation therapies administered as induction therapy have driven a trend of more aggressive operations in patients with locally advanced pancreatic ductal adenocarcinoma (PDAC) that was historically considered technically unresectable. Herein, we present a technical report describing our surgical experience of tumors considered locally advanced with long segment encasement of the superior mesenteric vein (SMV), celiac axis (CA), or the inferior pancreaticoduodenal artery (IPDA) or gastroduodenal artery (GDA) preluding distal pancreatectomy-celiac axis resection (DP-CAR). The option then remains to keep the mesocaval shunt and implant the other branch into the portal vein or to transpose the mesocaval shunt to the portal vein. [Extracted from the article]

BACKGROUND Hyperandrogenemia is associated with several clinical disorders in which both reproductive dysfunction and metabolic changes may coexist [i.e. polycystic ovary syndrome (PCOS), obesity and congenital adrenal hyperplasia]. Moreover, there is growing evidence that the elevated levels of circulating androgens in obese girls may lead to an increased neuroendocrine drive to the reproductive axis, similar to that associated with PCOS. METHODS To test whether androgen exposure in the childhood and adolescent period could lead to pubertal alterations in LH secretory patterns, female rhesus monkeys received subcutaneous testosterone implants prepubertally beginning at 1 year of age, maintaining a 3.7-fold increase (P = 0.001) in circulating testosterone levels over cholesterol-implant controls (n = 6/group) into the post-pubertal period. In early adulthood, pulsatile secretion of LH was measured over 12 h during the early follicular phase of a menstrual cycle, and responsiveness of the pituitary to gonadotrophin-releasing hormone was determined. In addition, ultrasounds were performed to assess ovarian morphology and glucose tolerance testing was performed to assess insulin sensitivity. RESULTS The timing of menarche was similar between groups. Testosterone-treated animals had a significantly greater LH pulse frequency during the early follicular phase compared with controls (P = 0.039) when measured at 5 years of age. There was a larger LH response to GnRH when testosterone-treated animals were 4 years of age (P = 0.042), but not when the animals were 5 years old (P = 0.57). No differences were seen in insulin sensitivity or ovarian morphology, and the groups showed similar rates of ovulation in early adulthood. CONCLUSIONS Exposure to increased levels of androgens over the course of pubertal development appears to trigger physiological changes in the neural drive to the reproductive axis that resemble those of obese hyperandrogenemic girls in early adulthood and are characteristic of PCOS. [ABSTRACT FROM PUBLISHER]

Abstract: This study examined whether regular exercise training, at a level that would be recommended for middle-aged people interested in improving fitness could lead to improved cognitive performance and increased blood flow to the brain in another primate species. Adult female cynomolgus monkeys were trained to run on treadmills for 1 h a day, 5 days a week, for a 5 month period (n=16; 1.9±0.4 miles/day). A sedentary control group sat daily on immobile treadmills (n=8). Half of the runners had an additional sedentary period for 3 months at the end of the exercise period (n=8). In all groups, half of the monkeys were middle-aged (10–12 years old) and half were more mature (15–17 years old). Starting the fifth week of exercise training, monkeys underwent cognitive testing using the Wisconsin General Testing Apparatus (WGTA). Regardless of age, the exercising group learned to use the WGTA significantly faster (4.6±3.4 days) compared to controls (8.3±4.8 days; P=0.05). At the end of 5 months of running monkeys showed increased fitness, and the vascular volume fraction in the motor cortex in mature adult running monkeys was increased significantly compared to controls (P=0.029). However, increased vascular volume did not remain apparent after a 3-month sedentary period. These findings indicate that the level of exercise associated with improved fitness in middle-aged humans is sufficient to increase both the rate of learning and blood flow to the cerebral cortex, at least during the period of regular exercise. [Copyright &y& Elsevier]

Abstract: Female cynomolgus monkeys exhibit different degrees of reproductive dysfunction with moderate metabolic and psychosocial stress. When stressed with a paradigm of relocation and diet for 60 days or two menstrual cycles, highly stress resilient monkeys (HSR) continued to ovulate during the stress cycles whereas stress sensitive monkeys (SS) did not. After cessation of stress, monkeys characterized as HSR or SS were administered placebo (PL) or S-citalopram (CIT) for 15 weeks at doses that normalized ovarian steroid secretion in the SS animals and that maintained blood CIT levels in a therapeutic range. After euthanasia, the brain was perfused with 4% paraformaldehyde. The pontine midbrain was blocked and sectioned at 25 μm. The expression of four genes pivotal to serotonin neural function was assessed in the four groups of monkeys (n=4/group). Fev (fifth Ewing variant) ETS transcription factor, tryptophan hydroxylase 2 (TPH2), the serotonin reuptake transporter (SERT), and the 5HT1A autoreceptor were determined at 7–8 levels of the dorsal raphe nucleus with in situ hybridization (ISH) using radiolabeled- and digoxygenin-incorporated riboprobes. Positive pixel area and cell number were measured with Slidebook 4.2 in the digoxigenin assay for Fev. Optical density (OD) and positive pixel area were measured with NIH Image software in the radiolabeled assays for TPH2, SERT and 5HT1A. All data were analyzed with two-way ANOVA. SS monkeys had significantly fewer Fev-positive cells and lower Fev-positive pixel area in the dorsal raphe than HSR monkeys. SS monkeys also had significantly lower levels of TPH2, SERT and 5HT1A mRNAs in the dorsal raphe nucleus than HSR monkeys. However, CIT did not alter the expression of either Fev, TPH2, SERT or 5HT1A mRNAs. These data suggest that SS monkeys have fewer serotonin (5-HT) neurons than HSR monkeys, and that they have deficient Fev expression, which in turn, leads to deficient TPH2, SERT and 5HT1A expression. In addition, the therapeutic effect of CIT is probably achieved through mechanisms other than alteration of 5-HT-related gene expression. [Copyright &y& Elsevier]

Abstract: Female cynomolgus monkeys exhibit different degrees of reproductive dysfunction with moderate metabolic and psychosocial stress. In this study, the expression of four genes pivotal to serotonin neural function was assessed in monkeys previously categorized as highly stress resistant (n=3; normal menstrual cyclicity through two stress cycles), medium stress resistant (n=5; ovulatory in the first stress cycle but anovulatory in the second stress cycle), or low stress resistant (i.e. stress-sensitive; n=4; anovulatory as soon as stress is initiated). In situ hybridization and quantitative image analysis was used to measure mRNAs coding for SERT (serotonin transporter), 5HT1A autoreceptor, MAO-A and MAO-B (monoamine oxidases) at six levels of the dorsal raphe nucleus (DRN). Optical density (OD) and positive pixel area were measured with NIH Image software. In addition, serotonin neurons were immunostained and counted at three levels of the DRN. Finally, each animal was genotyped for the serotonin transporter long polymorphic region (5HTTLPR). Stress sensitive animals had lower expression of SERT mRNA in the caudal region of the DRN (P&#60;0.04). SERT mRNA OD in the caudal DRN was positively correlated with serum progesterone during a pre-stress control cycle (P&#60;0.0007). 5HT1A mRNA OD signal tended to decline in the stress-sensitive group, but statistical difference between averages was lacking in analysis of variance. However, 5HT1A mRNA signal was positively correlated with control cycle progesterone (P&#60;0.009). There was significantly less MAO-A mRNA signal in the stress-sensitive group (P&#60;0.007) and MAO-A OD was positively correlated with progesterone from a pre-stress control cycle (P&#60;0.007). MAO-B mRNA exhibited a similar downward trend in the stress-sensitive group. MAO-B OD also correlated with control cycle progesterone (P&#60;0.003). There were significantly fewer serotonin neurons in the stress-sensitive group. All animals contained only the long form of the 5HTTLPR. Thus, all serotonin-related mRNAs examined in the dorsal raphe to date were lower (SERT, MAO-A) or exhibited a lower trend (5HT1A, MAO-B) in the stress sensitive animals, which probably reflects the lower number of serotonin neurons present. [Copyright &y& Elsevier]

B Presenter: b Alina Hasanain MD | Johns Hopkins University School of Medicine B Background: b Outcomes in patients with pancreatic ductal adenocarcinoma (PDAC) remain poor and are predominantly driven by aggressive systemic disease. The aim of the current study was to assess whether CTC characteristics are associated with the impact of a delay in initiation of adjuvant therapy on patient outcomes. [Extracted from the article]

B Presenter: b Ammar Javed MD | Johns Hopkins University School of Medicine B Background: b Improvements in systemic therapies available for PDAC have resulted in increased utilization and prolonged survival. B Conclusion: b Systemic therapy type, sequence, and duration affect survival in patients with PDAC. In patients who receive less than four months of chemotherapy prior to surgery administration of adjuvant therapy is associated with longer survival. [Extracted from the article]

The article focuses on the complications of biliary anastomotic strictures (BAS) post pancreaticoduodenectomy (PD), and talks of study conducted by Johns Hopkins University School of Medicine, development of postoperative pancreatic fistula (POPF), and independent predictors such as jaundice.