Surgical Management of Solid Pseudopapillary Tumor of the Pancreas.

BACKGROUND AND OBJECTIVES: Although solid pseudopapillary tumor (SPT) of the pancreas is rare, its diagnosis has increased severalfold in the past decades. We present our experience in the management of SPT, including a patient who experienced tumor rupture during laparoscopy pancreatic resection. METHODS: Data on all patients with SPT who were subjected to surgical treatment were retrospectively obtained. RESULTS: Of 20 patients evaluated, 17 (85%) were females. The mean age was 31 years. Tumor size varied from 2.7 × 1.5 to 13.5 × 10.0 cm, with a mean of 6.4 × 7.6 cm. The most common location was the tail and/or body of the pancreas (14 patients [70%]). Pancreatic tumor resection was performed in 19 patients (50%). The type of resection depended on tumor location and size: distal pancreatectomy (n = 13), pancreatoduodenectomy (n = 5), and central pancreatectomy (n = 1) Pancreatic resection was performed via laparoscopy in 7 patients who underwent distal pancreatectomy. Tumor resection was not performed in only 1 patient (5%), due to invasion of mesenteric vessels and presence of liver metastases. One patient had tumor rupture during laparoscopic resection, with no apparent macroscopic dissemination of the tumor. All 19 patients who underwent SPT resection had no tumor recurrence, including a patient with capsule invasion and another patient with tumor rupture during surgical dissection. The mean follow-up time was 38 months (range, 6-72 months). CONCLUSION: Complete SPT resection is possible in most patients, with a low recurrence rate. Because of its large size, laparoscopic resection of SPT's should be performed only by experienced surgeons to avoid tumor rupture.

Preemptive living donor kidney transplantation: do the benefits extend to all recipients?

BACKGROUND: Preemptive kidney transplantation (prior to the institution of dialysis) avoids the morbidity and mortality of dialysis; however, detailed studies of high-risk patients are lacking. The aim of the current study was to compare recent outcomes of preemptive (P) versus nonpreemptive (NP) living donor kidney transplantation with an emphasis on high-risk recipients. METHODS: We retrospectively analyzed 438 sequential solitary living donor kidney transplants at our institution between January 2000 and December 2002. In all, 44% were preemptive. NP recipients were dialyzed for 21+/-36 months (range 1-312 months). RESULTS: Overall, three-year patient survival was similar in the NP and P groups. When stratified by diabetes and age >65 years, P and NP recipients again showed similar survival. Death-censored three-year graft survival was better in the P group (97% vs. 90%, P=0.01), but was not significant by multivariate analysis. Delayed graft function was more frequent in NP vs. P (10% vs. 4%; P=0.01), but other early complications were similar including: acute rejection, 16% vs. 11% (P=0.11); primary nonfunction, 3% vs. 2% (P=0.38); and wound complications, 19% vs. 17% (P=0.54). Glomerular filtration rate at three years was similar in the two groups (53+/-23 preemptive vs. 52+/-20 ml/min nonpreemptive; P=0.37). CONCLUSION: With prompt referral and workup, preemptive kidney transplantation can be performed successfully in a large percentage of renal allograft recipients. Preemptive transplantation avoids unnecessary dialysis and should be emphasized as initial therapy for many patients with end-stage renal disease.

Omega-3 fatty acids improve appetite in cancer anorexia, but tumor resecting restores it.

BACKGROUND: Tumor growth leads to cancer anorexia that is ameliorated using omega-3 fatty acids (omega-3FA). We hypothesize that omega-3FA modulates up-regulation of hypothalamic orexigenic neuropeptide Y (NPY) and down-regulation of anorexigenic alpha melanocyte-stimulating hormone (alpha-MSH) and serotonin 1B receptors (5-HT(1B)-receptors) in tumor-bearing rats. METHODS: Twenty-eight tumor-bearing rats were fed either chow (TB-Control) or omega-3FA (TB-omega-3FA). When anorexia developed in TB-Control rats, they and a cohort of TB-omega-pi-3 rats were killed. The rest had their tumor resected (R-Control and R-omega-3FA), and when anorexic TB-Controls normalized their food intake, brains were removed for hypothalamic immunocytochemical study of NPY, alpha-MSH, and 5-HT(1B)-receptor antibodies concentrations. Comparison among slides were assessed by image analysis and analyzed by ANOVA and t test. RESULTS: At anorexia, hypothalamic NPY in arcuate nucleus (ARC) increased by 38% in TB-omega3FA versus TB-Control, whereas alpha-MSH decreased 64% in ARC and 29% in paraventricular nucleus (PVN). Omega-3FA diet in anorexia (TB-omega-3FA vs R-omega-3FA) produced similar qualitative changes of NPY (22% increase) and alpha-MSH (31% decrease) in ARC, with concomitant decrease of 37% in 5-HT(1B)-receptors in PVN, confirming the influence of omega-3FA on the hypothalamic food intake modulators. However, after tumor resection (TB-Control vs R-Control) a 97% increase in NPY and a 62% decrease in alpha-MSH occurred that was significantly greater than in rats fed omega-3FA diet. CONCLUSION: Tumor resection and omega-3FA modifies hypothalamic food intake activity, up-regulating NPY and down-regulating alpha-MSH and 5-HT(1B)-receptors. Tumor resection in anorexic rats on chow diet restored hypothalamic NPY, alpha-MSH, and food intake quantitatively more than in rats fed omega3FA diet.

Changes in GI hormones and their effect on gastric emptying and transit times after Roux-en-Y gastric bypass in rat model.

BACKGROUND: We determined whether Roux-en-Y gastric bypass (RYGB)-induced protracted weight loss is associated with an increase in anorectic peptide YY (PYY) and decreased gastrointestinal (GI) motility. METHODS: RYGB and control sham-operated GI intact obese (SO Obese) and sham-operated GI intact pair-fed (PF) rats were studied. Postoperatively, body weight (BW) and food intake were measured for 90 days. Rats were killed to measure PYY, ghrelin, cholecystokinin (CCK), and glucagonlike peptide-1 (GLP-1). Ninety-day food intake trends were examined by quadratic trend analysis. On the basis of a 28-day weight loss rate, PYY also was measured at 14 and 28 days. Peak 28-day PYY results corresponded with peak BW loss rate; thus, gastric emptying (GE) and intestinal transit time were measured. Data were analyzed by analysis of variance and Tukey's pairwise multiple comparison. RESULTS: At 90 days, BW in SO Obese versus PF versus RYGB rats was 801 +/- 15 g versus 661 +/- 24 g versus 538 +/- 32 g respectively (P < .05). Concentrations of plasma PYY were increased, while plasma ghrelin was decreased in RYGB versus SO Obese and PF (P < .05). CCK and GLP-1 were unchanged. In RYGB versus controls, PYY was increased at 14 and 28 days but was most elevated at 28 days. In RYGB versus controls, GE was delayed (P < .05) and intestinal transit time was longer (P < .05). CONCLUSIONS: After RYGB, an increase in PYY and a decrease in ghrelin occurred, probably explaining the decrease in food intake, the slower GE and transit time, which contributed to weight loss. Longitudinal studies can be performed with the use of our RYGB model, providing insight into weight loss mechanisms by generating long-term follow-up data currently not available in human studies.

Effects of omega-3 fatty acids on orexigenic and anorexigenic modulators at the onset of anorexia.

In cancer anorexia, a decrease in food intake (FI) occurs concomitant with changes in orexigenic peptides such as neuropeptide Y (NPY) and anorexigenic peptides such as alpha-melanocyte-stimulating hormone (alpha-MSH) and anorexigenic neurotransmitter serotonin. omega-3 Fatty acid (omega-3FA) inhibits cytokine synthesis, and delays tumor appearance, tumor growth, and onset of anorexia in tumor-bearing rats. We hypothesize that, in cancer anorexia, omega-3FA is associated with quantitative reversal of hypothalamic NPY, alpha-MSH, and serotonin receptor (5-HT(1B)-receptor) enhancing FI. Fischer rats were divided into: MCA tumor bearing fed chow (TB-Chow) or omega-3FA diet (TB-omega-3FA) and controls: non-tumor bearing fed chow (NTB-Chow) or omega-3FA diet (NTB-omega-3FA). Rats were euthanized at anorexia and brains were removed for hypothalamic immunohistochemical study, using NPY, alpha-MSH, and 5-HT(1B)-receptor-specific antibodies and slides assessed by image analysis. Immunostaining specificity was controlled by omission of primary or secondary antibodies and pre-absorption test. At anorexia, FI decreased (P < 0.05) in TB-Chow but did not change in TB-omega-3FA rats. In TB-omega-3FA vs. TB-Chow, NPY immunoreactivity increased 38% in arcuate nucleus (ARC; P < 0.05), and 50% in magnocellular paraventricular nucleus (mPVN; P < 0.05). alpha-MSH decreased 64% in ARC and 29% in mPVN (P < 0.05). 5-HT(1B)-receptor immunoreactivity decreased 13% only in supraoptic nucleus (P < 0.05). No immunoreactivity was found in the control sections. omega-3FA modified hypothalamic peptides and 5-HT-(1B)-receptor immunoreactivity at anorexia, concomitant with an increase in FI, were probably mediated by omega-3FA inhibition of tumor-induced cytokines.

Hypothalamic 5-HT1B-receptor changes in anorectic tumor bearing rats.

Serotonin (5-HT) is an anorectic monoamine and its regulatory effects on feeding are mediated primarily via 5-HT1B-receptors localized in the hypothalamic nuclei, which, apart from the brain stem, are among the most crucial areas of food intake regulation. The distribution of 5-HT1B-receptors in the hypothalamic nuclei was studied in tumor-bearing (TB) rats at the onset of anorexia and in sham-operated control rats, using the peroxidase-anti-peroxidase immunocytochemical method and specific polyclonal antiserum. Semiquantitative image analysis of 5-HT1B-receptor immunostaining was performed on high-resolution digital photomicrographs using the NIH Scion Image analysis program and the data were compared using Student's t-test. Immunostaining detected 5-HT1B-receptor proteins in the same hypothalamic structures in the Controls as in the TB rats. Qualitative and semiquantitative analysis revealed a significant increase in 5-HT1B-receptor expression in the magnocellular neurons of paraventricular and supraoptic hypothalamic nuclei in TB rats versus Controls. In contrast, changes were not significant in the parvocellular portion of paraventricular nucleus or in the lateral hypothalamus including perifornical region. These findings emphasize serotonin's influence on the magnocellular hypothalamic nuclei during developing of cancer anorexia, which is associated with a decrease in food intake.

Normalization of hypothalamic serotonin (5-HT 1B) receptor and NPY in cancer anorexia after tumor resection: an immunocytochemical study.

Tumor growth leads to anorexia and decreased food intake, the regulation of which is via the integrated hypothalamic peptidergic and monoaminergic system. Serotonin (5-HT), an anorectic monoamine acts primarily via 5-HT 1B-receptors in hypothalamic nuclei while neuropeptide Y (NPY) acts an orexigenic peptide. We previously reported that 5-HT 1B-receptors are up regulated while NPY is down regulated in tumor-bearing (TB)-related anorexia, contributing to food intake reduction. In anorectic TB rats we hypothesize that after tumor resection when food intake has reverted to normal, normalization of 5-HT 1B-receptor and NPY will occur. The aim of this study was to demonstrate normalization of these hypothalamic changes compared to Controls. In anorectic tumor-bearing rats after tumor resection (TB-R) and in sham-operated (Control) rats, distribution of 5-HT 1B-receptors and NPY in hypothalamic nuclei was analyzed using peroxidase antiperoxidase immunocytochemical methods. Image analysis of immunostaining was performed and the data were statistically analyzed. Immunostaining specificity was controlled by omission of primary or secondary antibodies and pre-absorption test. Our results show that after TB-R versus Controls a normalization of food intake, 5-H-1B-receptor and NPY expression in the hypothalamus occurs. These data, discussed in context with our previous studies, support the hypothesis that tumor resection results not only in normalization of food intake but also in reversible changes of anorectic and orexigenic hypothalamic modulators.

Neuropeptide Y, alpha-melanocyte-stimulating hormone, and monoamines in food intake regulation.

Obesity is increasing in severity and prevalence in the United States and represents a major public health issue. No effective pharmacologic treatment leading to sustained weight loss currently exists. The growing interest in the regulation of food intake stems from the current drug treatments for obesity, almost all of which interfere with the monoamine system. Our knowledge of potential interactions between the orexigenic and anorexigenic pathways is limited and fragmented, making the development of targeted drug therapy for obesity difficult. The present review of the interaction of neuropeptides and monoamines emphasizes the complexity of the central mechanisms that regulate feeding behavior. Two main systems are implicated in food intake regulation: neuropeptide Y (NPY) and pro-opiomelanocortin. alpha-Melanocyte-stimulating hormone is a tridecapeptide cleaved from pro-opiomelanocortin that acts to inhibit food intake. The predominant NPY orexigenic receptors are NPY-Y1 and NPY-Y5, and the two anorexigenic melanocortin receptors involved in hypothalamic food intake control are MC3-R and MC4-R. Both neuropeptides interact with monoamines in the hypothalamus to control physiologic states such as hunger, satiation, and satiety. Serotonin suppresses food intake and body weight, acting mainly through the serotonin 1B receptor. Dopamine regulates hunger and satiety by acting in specific hypothalamic areas, through the D1 and D2 receptors. Noradrenaline activation of alpha1- and beta2-adrenoceptors decreases food intake, and stimulation of the alpha2-adrenoceptor increases food intake. A better understanding of the detailed mechanisms underlying the pathogenesis of hyperphagia and hypophagia is needed to develop new therapeutic approaches to obesity.

Gene expression profiles post Roux-en-Y gastric bypass.

BACKGROUND: The hypothalamus is involved in regulation of food intake (FI) and fat deposition. Molecular mechanisms of weight loss after Roux-en-Y gastric bypass (RYGB) were studied by correlating changes in gene expression profiles in hypothalamic arcuate nucleus (ARC) and subcutaneous abdominal fat (SAF). METHOD: Diet-induced obese rats were divided into RYGB, sham-operated (SO-Obese), and sham-operated pair-fed (PF) groups. A non-obese group on a regular chow diet served as control. Body weight (BW) and FI were measured. Rats were killed 10 days after the operation. Plasma was analyzed for biochemical indices, ARC and SAF were analyzed for gene expression profiles. Body SAF was also weighed. Data were analyzed by ANOVA and factor analysis. RESULTS: BW and FI decreased in RYGB versus SO-Obese, as reflected by decreased SAF (53%). Genes similarly expressed in ARC and SAF after RYGB were limited to several genes that predominantly related to metabolic pathways of carbohydrate, fat, neuropeptide, and cytokines. These expression profiles were similar to those seen in chow control and to those seen in a comparison of PF and SO-Obese. CONCLUSIONS: RYGB-induced weight loss is associated with changes in gene profile expressions that could influence metabolic changes, contributing to weight loss.

Changes in hypothalamic neuropeptide Y and monoaminergic system in tumor-bearing rats: pre- and post-tumor resection and at death.

BACKGROUND: Cancer anorexia is influenced by the neuropeptidergic and monoaminergic systems. We hypothesize that serotonin (5-HT), dopamine (DA) and neuropeptide Y (NPY) concentrations in paraventricular (PVN), ventromedial (VMN), and lateral hypothalamus (LHA) areas are abnormal in tumor-bearing rats. METHODS: Fifty-five Fischer rats (240-280 g) were divided into MCA tumor-bearing (TB), nontumor-bearing (NTB), pair-fed (PF), TB sacrificed at the end of experiment (TB-Terminal), TB resection (TB-Resection), NTB sham-operated (NTB-Sham) and pair-fed sham-operated (PF-Sham) groups. Rats were sacrificed at onset of anorexia (TB, NTB, and PF) and 9 days after tumor resection (TB-Resection, NTB-Sham, PF-Sham, and TB-Terminal). Bilateral PVN, VMN, and LHA were harvested for NPY, 5-HT, and DA analyses. RESULTS: Food intake decreased in TB versus NTB (P < .05). In TB versus NTB, an increase of 5-HT in PVN and VMN occurred with a concomitant decrease in DA. NPY in PVN, VMN, and LHA decreased (P < .05). In TB-Resection versus NTB-Sham, 5-HT, DA, NPY, and FI normalized after tumor resection. CONCLUSIONS: Cancer anorexia is associated with abnormal serotonin, dopamine, and NPY concentrations, expressed by an increase in 5-HT and a decrease in DA and NPY. After tumor resection, these alterations normalized, providing evidence that the levels of these substances change with anorexia in tumor-bearing rats.

Is obesity an inflammatory disease?

BACKGROUND: Most obese individuals have elevated concentrations of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), markers of inflammation closely associated with diabetes, hypertension, and stroke. HYPOTHESIS: Obesity is a low-grade inflammatory disease, and Roux-en-Y gastric bypass (RYGB) reduces biochemical markers of inflammation and modifies gene expression in hypothalamic food intake/energy-related nuclei and subcutaneous abdominal fat (SAF). METHODS: Obesity was induced in 24 3-week-old Sprague Dawley pups fed a high-energy diet (HED). Three groups (n = 8/group) were studied: RYGB, sham-operated pair-fed, and sham-operated ad libitum HED. Controls were nonobese rats fed chow (n = 6). Rats were killed 10 days after operation, and blood was collected to measure corticosterone and SAF and mesenteric fat to measure IL-6, TNF-alpha, and corticosterone. Total mRNA from arcuate nucleus and SAF purified for gene expression profiling. Data were analyzed with analysis of variance, Mann-Whitney test, and t test. RESULTS: Before operation, the body weight of the obese groups was 493 +/- 7 g and control = 394 +/- 12g. The 10-day postoperative weight was RYGB = 417 +/- 21 g, pair-fed = 436 +/- 14 g, and ad libitum HED = 484 +/- 15 g. Mesenteric and SAF weight decreased in RYGB. Mesenteric/SAF ratio of IL-6, TNF-alpha, corticosterone, and gene profiling showed decrease of inflammation after RYGB. CONCLUSIONS: Gastric bypass reduces biochemical markers of inflammation, suggesting that obesity is an inflammatory condition.

Nicotine infusion into rat ventromedial nuclei and effects on monoaminergic system.

Nicotine increases satiety and reduces food intake (FI). We hypothesize that nicotine influences FI via alteration of serotonin (5HT) and dopamine (DA) concentration in ventromedial nucleus (VMN) and lateral hypothalamic area (LHA). Microdialysis cannulas were implanted into ipsilateral VMN and contralateral LHA. Nicotine or vehicle was infused for 60 min into VMN of overnight food-deprived rats, followed by ad lib food for 40 min. Hypothalamic changes in 5HT and DA concentrations were measured every 20 min. Intra-VMN nicotine induced a long-lasting increase in 5HT concentration and an increase in DA for a short duration in the VMN, associated with an increase in 5HT in the LHA. Our data suggest that the nicotine-induced hypophagia correlates with VMN and LHA monoaminergic changes.

Tumor anorexia: effects on neuropeptide Y and monoamines in paraventricular nucleus.

Paraventricular (PVN) concentrations of neuropeptide Y (NPY), serotonin (5-HT) and dopamine (DA) in anorectic tumor-bearing (TB) rats were measured before and after tumor resection. At onset of anorexia in TB versus non-tumor bearing (NTB) Controls 5-HT increased from 12.19+/-0.49 pg/microg to 14.89+/-0.81 pg/microg ( P<0.05 ) while DA and NPY decreased from 7.34+/-0.42 pg/microg to 4.97+/-0.56 pg/microg and 23.47+/-4.27 pg/microg to 13.64+/-1.44 pg/microg, respectively ( P<0.05 ). After tumor resection, these neuromediators normalized when compared to sham-operated NTB rats. NTB pair-fed Controls were also studied. We conclude that the increased 5-HT and the decreased DA and NPY concentrations in PVN are associated with cancer anorexia and that the NPY food stimulatory effect is linked to serotoninergic and dopaminergic systems in hypothalamus.

Effects of omega-3 fatty acid supplementation on tumor-bearing rats.

BACKGROUND: Dietary fish oil (rich in omega-3 fatty acids: eicosapentaenoic acid and docosahexaenoic acid) suppresses synthesis and activity of proinflammatory cytokines that induce anorexia. We hypothesized that dietary fish oil reverses the feeding pattern of tumor anorexia, increasing food intake and retarding tumor growth. STUDY DESIGN: Thirty-two Fischer rats were placed in Automated Eater Meter cages and randomly divided into four groups: tumor bearing (TB) rats eating normal chow diet (TB-Chow); TB rats eating chow diet supplemented with omega-3 fatty acids (TB-omega-3FA); Controls, non-tumor bearing (NTB) rats eating normal chow (NTB-Chow); and NTB rats with omega-3 fatty acid supplementation (NTB-omega-3FA). Doses of 10(6) methylcholanthrene (MCA) sarcoma cells were subcutaneously injected in TB rats. Daily food intake, meal size (MZ), meal number (MN), body weight, and tumor volume were measured, and rats were euthanized at onset of anorexia. Data were statistically analyzed using analyses of variance (ANOVA) and t-tests. Data are reported as mean +/- SE. RESULTS: Tumor appeared significantly earlier in TB-Chow than in TB-omega-3FA rats (7.5 +/- 0.3 days versus 11.6 +/- 0.8 days, p < 0.05). Daily food intake declined significantly in TB-Chow versus TB-omega-3FA rats 18 days after tumor inoculation and, at onset of anorexia, was 9.41 +/- 1.77 g/day versus 13.32 +/- 0.81 g/day, p < 0.05. Food intake decreased initially by decrease in meal number (at day 15) followed by a decrease in meal size (at day 18). At onset of anorexia, meal size and meal number were significantly decreased in TB-Chow versus TB-omega-3FA rats (0.75 +/- 0.067 g/meal versus 1.05 +/- 0.08 g/meal, p < 0.05) and (9.5 +/- 1.32 versus 12.79 +/- 0.93 meals/day, p < 0.05), respectively. Tumor volume was significantly smaller in TB-omega-3FA versus TB-Chow rats (7.6 +/- 0.6 cm(3) versus 16.5 +/- 1.0 cm(3), p < 0.05), as was tumor weight (7.5 +/- 2.2 g versus 18.1 +/- 1.6 g, p < 0.05). CONCLUSIONS: In TB rats, omega-3FA improved food intake; restored normal eating pattern, delayed onset of anorexia, tumor appearance, and growth; and prevented body weight loss. Supplementation of omega-3 fatty acids has therapeutic potential in cancer anorexia.

Neurobiologic changes in the hypothalamus associated with weight loss after gastric bypass.

BACKGROUND: Effects of Roux-en-Y gastric bypass (RYGB) on hypothalamic food intake regulation have not been investigated. The hypothalamic arcuate nucleus (ARC) and the magnocellular (m) and parvocellular (p) parts of the paraventricular nucleus (PVN) regulate hunger and satiety, and are under control of the orexigenic neuropeptide Y (NPY), and the anorexigenic alpha-melanocyte stimulating hormone (alpha-MSH) and serotonin (5-HT). We hypothesized that after RYGB, weight loss is associated with hypothalamic down regulation of NPY and up regulation of 5-HT and alpha-MSH. STUDY DESIGN: Obesity was induced in 12 Sprague Dawley rats using a high-energy diet for 7 weeks, and then the rats were divided into three groups (n = 4/group): RYGB, sham-operated pair-fed (PF), and sham-operated ad libitum (obese control). Ten days after operation, immunohistochemical quantification of NPY, alpha-MSH, and 5-HT(1B)-receptors in ARC and PVN was performed. Data were analyzed using ANOVA and Tukey's test. RESULTS: Body weight decreased in RYGB (417 +/- 21 g; mean +/- SE) and in PF (436 +/- 14 g) rats 10 days after operation compared with obese control rats (484 +/- 15 g; p < 0.05 for each comparison). NPY in ARC, pPVN, and mPVN decreased by 43%, 43%, and 61%, respectively in RYGB and by 55%, 42%, and 71% in PF, respectively, compared with obese controls (p < 0.05 for each pairwise comparison). RYGB versus PF did not show differences. alpha-MSH in ARC, pPVN and mPVN increased by 35%, 175%, and 67%, respectively in RYGB and by 29%, 162%, and 116% in PF, respectively, compared with obese controls (each p < 0.05). In mPVN, alpha-MSH significantly decreased by 23% in RYGB versus PF (p < 0.05). 5-HT-(1B)-receptor in pPVN increased by 58% in RYGB and by 26% in PF, compared with obese controls (p < 0.05). Compared with obese controls, 5HT-(1B)-receptor in mPVN increased by 39% in RYGB (p < 0.05) and by 9% in PF (p > 0.05). An increase of 5-HT-(1B)-receptor in pPVN and mPVN occurred in RYGB versus PF (p < 0.05). CONCLUSIONS: Obese rats that undergo weight loss after RYGB demonstrate changes in hypothalamic down regulation of NPY and up regulation of alpha-MSH and serotonin.

A surgical rat model of human Roux-en-Y gastric bypass.

Obesity affects 30% of the United States population and its detrimental effects are obesity-related metabolic diseases. For patients refractory to conventional weight loss therapy, gastric bypass surgery is one of the proven methods for inducing a sustained weight loss and reversing the metabolic sequelae of obesity. To understand the mechanisms of weight loss and the amelioration of related metabolic comorbid conditions, a reproducible animal model is needed. We report our developmental experience with rat models of sequential Roux-en-Y gastric bypass after reproducing the diet-induced obesity that characterizes the hallmarks of human obesity. Four experiments were performed to induce weight reduction through successive modifications: In Experiment 1 a 20% stapled gastric pouch with a 16 cm biliary-pancreatic limb and a 10 cm alimentary limb accomplished sufficient weight loss within 10 days to ameliorate metabolic changes associated with obesity, but the occurrence of gastrogastric fistulas prevented sustained weight loss; in Experiment 2 the model was improved by dividing the stomach to avoid gastrogastric fistula, but again sustained weight loss was not achieved; in Experiment 3 the biliary-pancreatic limb was lengthened from 16 to 30 cm, reducing the common channel to approximately 18 cm. Sustained weight loss was achieved for 28 days. In Experiment 4 the model in Experiment 3 was modified by dividing the stomach between two rows of staples. Sustained weight loss was observed for 67 days. We developed a reproducible rat model of Roux-en-Y gastric bypass. The existence of this model opens a new field of research in which to study the metabolic sequelae of obesity and the mechanisms of weight loss.

Liver transplantation in a patient with complex anomaly of the inferior vena cava.

BACKGROUND: After the introduction of noninvasive imaging exams, congenital anomalies of the inferior vena cava (IVC) have become more commonly recognized. We report the first successful orthotopic liver transplantation (OLT) performed in an asymptomatic adult with complex IVC anomaly: duplication of the infrarenal IVC, azygos continuation of the IVC, agenesia of the hepatic portion of the IVC and presence of several anomalous veins communicating the common iliac vein and the IVC of one side with the contralateral side. METHODS: This complex anomaly was diagnosed with a venous abdominal angio CT. RESULTS: At liver transplantation, the short suprahepatic portion of the IVC was identified and clamped. The right, middle, and left hepatic veins were sectioned and joined in a single, wide cuff, using venoplasty. This single orifice was anastomosed to the suprahepatic IVC of the new liver. No venovenous bypass was employed. The patient had an uneventful postoperative course. A post transplantation venous abdominal angio CT showed normal blood flow at the anastomosis of the hepatic veins of the receptor and the IVC of the new liver. CONCLUSIONS: This report is important to alert liver transplant teams of the possibility of complex IVC in asymptomatic adult individuals. Identification of these anatomical anomalies is vital to reduce the risk of serious hemorrhage and other operative complications during OLT.

Omega-3 fatty acids and anorexia.

PURPOSE OF REVIEW: To review the mechanisms of action of omega-3 fatty acids and their role in the brain, as well as their therapeutic implications in anorexia. RECENT FINDINGS: Recent studies have demonstrated that omega-3 fatty acids modulate changes in the concentrations and actions of several orexigenic and anorexigenic neuropeptides in the brain, including neuropeptide Y, alpha-melanocyte stimulating hormone and the neurotransmitters serotonin and dopamine. In patients with acute and chronic inflammatory conditions, low tissue concentrations of omega-3 fatty acids and high concentrations of proinflammatory cytokines are found, in association with anorexia and decreased food intake. The data suggest that omega-3 fatty acid supplementation suppresses proinflammatory cytokine production and improves food intake by normalizing hypothalamic orexigenic peptides and neurotransmitters. SUMMARY: Based on current data, omega-3 fatty acid supplementation has a role in the treatment of anorexia by stimulating the production and release of orexigenic neurotransmitters in food intake regulatory nuclei in the hypothalamus.