Nutritional deficiencies after Roux-en-Y gastric bypass for morbid obesity often cannot be prevented by standard multivitamin supplementation

BACKGROUND: Despite the increasing use of Roux-en-Y gastric bypass (RYGBP) in the treatment of morbid obesity, data about postoperative nutritional deficiencies and their treatment remain scarce. OBJECTIVE: The aim of this study was to evaluate the efficacy of a standard multivitamin preparation in the prevention and treatment of nutritional deficiencies in obese patients after RYGBP. DESIGN: This was a retrospective study of 2 y of follow-up of obese patients after RYGBP surgery. Between the first and the sixth postoperative months, a standardized multivitamin preparation was prescribed for all patients. Specific requirements for additional substitutive treatments were systematically assessed by a biologic workup at 3, 6, 9, 12, 18, and 24 mo. RESULTS: A total of 137 morbidly obese patients (110 women and 27 men) were included. The mean (+/-SD) age at the time of surgery was 39.9 +/- 10.0 y, and the body mass index (in kg/m(2)) was 46.7 +/- 6.5. Three months after RYGBP, 34% of these patients required at least one specific supplement in addition to the multivitamin preparation. At 6 and 24 mo, this proportion increased to 59% and 98%, respectively. Two years after RYGBP, a mean amount of 2.9 +/- 1.4 specific supplements had been prescribed for each patient, including vitamin B-12, iron, calcium + vitamin D, and folic acid. At that time, the mean monthly cost of the substitutive treatment was $34.83. CONCLUSION: Nutritional deficiencies are very common after RYGBP and occur despite supplementation with the standard multivitamin preparation. Therefore, careful postoperative follow-up is indicated to detect and treat those deficiencies.

The role of the δ-opioid receptor in skin homeostasis and wound healing

Au regard des agressions environnementales constantes que la peau doit endurer, l'équilibre fragile entre l'expression et la répression des gènes épidermiques, nécessaire à la différentiation et la prolifération des kératinocytes, pourrait facilement être perturbé en l'absence des mécanismes de stabilisation robustes. La présence d'un système neuroendocrinien local est donc importante afin de coordonner une réponse aux éventuelles irritations. En effet, l'expression de plusieurs neurohormones, des neurotransmetteurs et des neuropeptides, y compris des dérivés pro-opiomélanocortine comme la ß-endorphine et [Met5]-enképhaline, ainsi que l'expression du récepteur 8-opioïde (DOR) a été démontré dans la peau. Cependant, les mécanismes moléculaires par lesquels ils modulent la fonction des kératinocytes sont mal connus. Le présent travail démontre que la voie de signalisation DOR active spécifiquement la voie ERK 1/2 MAPK dans les lignées cellulaires de kératinocytes humains, inhibant la prolifération des cellules et entraîne une diminution de l'épaisseur épidermique dans un modèle organotypique de peau. De plus, l'expression de DOR retarde nettement l'induction de la kératine 10 (KRT 10) et la kératine 1 (KRT 1) dans une modèle 2D de différentiation in vitro, et supprime l'induction de KRT 10 dans un modèle organotypique de peau. Ceci est accompagné de la dérégulation de l'involucrine (IVL), la loricrine (LOR) et la fïlaggrin (FLG), résultant en une induction nettement réduite de leur expression lors de l'initiation de la différentiation in vitro. De plus, POU2F3 a été identifié comme un facteur de transcription régulant les gènes de différentiation des kératinocytes modulés par DOR. Il a été démontré que la régulation négative de POU2F3 via la voie DOR-ERK affecte les principaux aspects de la fonction des kératinocytes. Toutefois, il est évident que des facteurs supplémentaires influencent la fonctionnalité de la voie DOR elle-même. Le calcium et le contact cellule-cellule augmentent la quantité des récepteurs à la surface cellulaire des kératinocytes. Les kératinocytes dont les récepteurs sont internalisés ne répondent pas de la même manière que ceux possédant des récepteurs fonctionnels localisée à la membrane. Ce travail suggère que lors de signaux intrinsèques ou extrinsèques spécifiques, les kératinocytes sont capable de répondre via le système opioïdergique neuro-epidermique. Cette réponse doit être spatialement et temporairement contrôlée afin d'éviter un déséquilibre de l'homéostasie épidermique et un retard de cicatrisation. La compréhension de ce processus très complexe pourrait permettre à terme le développement de meilleurs traitements des affections cutanées pathologiques. En complément des études précédentes sur des souris DOR-défïcientes, ces données suggèrent que l'activation de DOR dans les kératinocytes humains influence la morphogenèse et l'homéostasie de l'épiderme, et pourrait jouer un rôle lors du processus de cicatrisation. - In view of the constant environmental assaults that the skin must endure, the delicate balance of an eloquent sequence of epidermal gene expression and repression, that is required for appropriate differentiation and proliferation of keratinocytes, might easily become derailed in the absence of robust stabilizing mechanisms. The presence of a local neuroendocrine system is thereby important to coordinate a response towards irritations. In fact, the expression of several neurohormones, neurotransmitters, and neuropeptides, including proopiomelanocortin derivatives, such as ß- endorphin and [Met5]-enkephalin has been shown in skin, as well as expression of the 6-opioid receptor (DOR). However, there is currently a lack of understanding of the molecular mechanisms by which their signalling modulates keratinocyte function. The present work demonstrates that DOR signalling specifically activates the ERK 1/2 MAPK pathway in human keratinocyte cell lines. This activation inhibits cell proliferation, resulting in decreased epidermal thickness in an organotypic skin model. Furthermore, DOR expression markedly delays induction of keratin intermediate filament Keratin 10 (KRT 10) and KRT 1 during in vitro differentiation, and abolishes the induction of KRT 10 in the organotypic skin model. This is accompanied by deregulation of involucrin (IVL), loricrin (LOR), and filaggrin (FLG), illustrated by a markedly reduced induction of their expression upon initiation of differentiation in vitro. Additionally, POU2F3 was identified as a transcription factor mediating the DOR induced regulation of keratinocyte differentiation related genes. It was revealed that DOR-mediated ERK-dependent downregulation of this factor affects key aspects of keratinocyte function. However, it is evident that additional triggers influence the functionality of the DOR itself. Calcium at concentrations above 0.1 mM and cell-cell contact both enhance the presence of receptor molecules on the keratinocytes cell surface. Keratinocytes with internalized receptor do not respond to DOR ligands in the same way as keratinocytes with a functional membrane localized receptor.

A single dose of intravenous esomeprazole decreases gastric secretion in healthy volunteers.

BACKGROUND: Data suggest that esomeprazole decreases gastric secretion. AIMS: To assess the effect of a single i.v. esomeprazole dose on gastric secretion volume 3 h after drug administration, as a primary endpoint, and to evaluate, as secondary endpoints, the reduction 1 and 5 h after dosing; time when the gastric pH was <2.5 and esomeprazole's safety. METHODS: In all, 23 healthy Helicobacter pylori-negative volunteers (10 men, 13 women, mean age 28.2 +/- 6) participated in this single-centre, randomized, double-blind, placebo-controlled, 2-way, single-dose cross-over study. In different sessions, volunteers received i.v. either esomeprazole 40 mg or placebo. An inserted double-lumen nasogastric tube perfused and aspirated gastric liquid. Mechanical fractioned aspiration measured secretion volume; aliquot spectrophotometry assessed gastric secretion volume lost to the duodenum. RESULTS: Three hours post-i.v. esomeprazole, average gastric secretion decreased by 77.6% (vs. baseline) compared to placebo. Values 1 and 5 h after dosing were 73.5% and 74.5%. Five hours after esomeprazole, the gastric pH was <2.5 3.9% of the time and 73.3% after placebo (P < 0.002). Esomeprazole was well-tolerated. No serious adverse events occurred. CONCLUSIONS: Intravenous esomeprazole decreases gastric secretions. The potential clinical impact in averting bronchoaspiration during anaesthesia induction and in intensive care patients should be investigated in further studies.

Redistribution of gastric blood flow by embolization of gastric arteries before esophagectomy.

Background. Anastomotic leak remains a common and potentially deleterious complication after esophagectomy. Preoperative embolization of the left gastric artery and splenic artery (PAE) has been suggested to lower anastomotic leak rates. We present the results of our 5-year experience with this technique.Methods. All patients undergoing PAE before esophagectomy since introduction of this technique in 2004 were compared in a 1: 2 matched-pair analysis with patients without PAE. Matching criteria were type of anastomosis, neoadjuvant treatment, comorbidity, and age. Data were derived from a retrospective chart review from 2000 to 2006 that was perpetuated as a prospective database up to date. Outcome measures were anastomotic leak, overall complications, and hospital stay.Results. Between 2000 and 2009, 102 patients underwent esophagectomy for cancer in our institution with an overall leak rate of 19% and a mortality of 8%. All 19 patients having PAE since 2004 were successfully matched 1: 2 to 38 control patients without PAE; both groups were similar regarding demographics and operation characteristics. Two PAE (11%) and 8 control patients (21%) had an anastomotic leak, but the difference was statistically not significant (p = 0.469). Overall and major complication rates for PAE and control group were 89% versus 79% (p = 0.469) and 37% versus 34% (p = 1.000), respectively. Median intensive care unit and hospital stay were 3 versus 3 days (p = 1.000) and 22 versus 17 days (p = 0.321), respectively.Conclusions. In our experience, PAE has no significant impact on complications and anastomotic leak in particular after esophagectomy. (Ann Thorac Surg 2011;91:1556-61) (C) 2011 by The Society of Thoracic Surgeons

Effects of gastric bypass and gastric banding on glucose kinetics and gut hormone release

Rapport de Synthèse : Introduction : outre son effet bénéfique sur le poids, la chirurgie bariatrique améliore de façon considérable l'homéostasie glucide chez les patients diabétiques. Cette amélioration survient très tôt dans la période post-opératoire, avant que le poids ne soit réduit de manière importante. De plus, les interventions chirurgicales qui "court-circuitent" une partie de l'intestin grêle, telle que le by-pass gastrique, apparaissent être plus efficaces que les interventions purement restrictives, telles que le cerclage gastrique. Objectifs : cette étude a pour but d'étudier la cinétique du glucose et la sécrétion d'hormones gastro-intestinales, consécutive à l'ingestion d'une dose charge de glucose, chez des patients opérés d'un by-pass ou d'un cerclage gastrique. Méthodes : nous avons comparé des groupes de femmes non diabétiques ayant bénéficié d'un by-pass gastrique (BPG, n=8) ou d'un cerclage gastrique (CG, n=6) à un groupe de femmes contrôles d'âge et de poids appariées n'ayant subi aucune intervention bariatrique (C, n=8). L'étude a été réalisée alors que le poids des volontaires était stable, soit entre 9 et 48 mois après le BPG, et 25 à 85 mois après le CG. Nous avons étudié, pendant les 4 heures qui ont suivies l'ingestion d'une dose charge de glucose; la cinétique du glucose ingéré et du glucose total à l'aide d'un glucose radio-activement marqué, ainsi que la cinétique de l'insuline et de différentes hormones gastro-intestinales. Résultats : l'apparition du glucose exogène dans la circulation systémique est plus rapide chez les patients opérés d'un BPG et s'accompagne d'une hyperglycémie postprandiale plus brève. La réponse insulinique est également plus précoce et plus importante que dans les deux autres groupes. S'agissant des hormones gastro-intestinales, on observe dans la période postprandiale une augmentation de PYY et de GLP-1 et une suppression de la grehline significativement plus importante après BPG. Discussion : ces différentes observations suggèrent que le BPG est associé à de profonds changements de la cinétique du glucose et des altérations de la régulation d'hormones gastro-intestinales. Les modifications susmentionnées apparaissant être secondaires aux modifications anatomiques consécutives au BPG, i.e. la mise "hors-circuit" de l'estomac distal et de l'intestin grêle proximal, compte tenu du fait qu'elles ne sont pas observées après CG. Finalement, la stimulation de PYY et de GLP-1 ainsi que la suppression postprandiale plus importante de ghréline est compatible avec la diminution spontanée de la prise alimentaire observée chez les patients opérés d'un BPG.

Laparoscopic Gastric Banding Outcomes Do Not Depend on Device or Technique. Long-Term Results of a Prospective Randomized Study Comparing the Lapband® and the SAGB®.

BACKGROUND: Gastric banding still represents one of the most widely used bariatric procedures. It provides acceptable weight loss in many patients, but has frequent long-term complications. Because different types of bands may lead to different results, we designed a randomized study to compare the Lapband® with the SAGB®. We hereby report on the long-term results. METHODS: Between December 1998 and June 2002, 180 morbidly obese patients were randomized between Lapband® or SAGB®. Weight loss, long-term morbidity, and need for reoperation were evaluated. RESULTS: Long-term weight loss did not differ between the two bands. Patients who maintained their band had an acceptable long-term weight loss of between 50 and 60 % EBMIL. In both groups, about half the patients developed long-term complications, with about 50 % requiring major redo surgery. There was no difference in the overall rates of long-term complications or failures between the two groups, but patients who had a Lapband® were significantly more prone to develop band slippage/pouch dilatation (13.3 versus 0 %, p < 0,001). CONCLUSIONS: Although in the absence of complication, gastric banding leads to acceptable weight loss; the long-term complication and major reoperation rates are very high independently from the type of band used or on the operative technique. Gastric banding leads to relatively poor overall long-term results and therefore should not be considered the procedure of choice for the treatment of morbid obesity. Patients should be informed of the limited overall weight loss and the very high complication rates.

A practical right-sided incisional gastropexy technique for treatment or prevention of gastric dilatation volvulus

Yhteenveto: Käytännöllinen oikeanpuoleinen viiltogastropeksia mahalaukun laajentumisen ja kiertymisen hoitona tai ennaltaehkäisynä

Roux-en-y Gastric Bypass is Superior to Gastric Banding in Non-superobese Patients. a Matched-case Study with Five-year Follow-up

Background: Roux-en-Y gastric bypass (RYGBP) and gastric banding (GB) are the two most popular bariatric procedures. Only few studies have compared their results and follow-up duration is usually limited to <3 years. Patients and Methods: Using our prospective bariatric database, we matched non-superobese GB to RYGBP patients for sex, age and BMI to RYGBP. Follow-up considered up to five years. Results: 442 patients were matched in 221 pairs. Mean age (38,6) and mean BMI (43) were identical. Overall operative morbidity was higher after RYGBP (17,2 versus 5,4 %, p<0,001), but major morbidity was similar (3,6 versus 2,2 %, p=0,57). More patients developed long-term complications after GB (43,9 % versus 19 %, p<0,001), and more required reoperations (24,4 % versus 12 %, p=0,001). After RYGBP, reoperations were mainly due to internal hernias (87 %), with no reversal, whereas 18,5 % of the GB patients required band removal. Even including only patients who retained their band, weight loss after RYGBP was better throughout the study period, with 5-year EBMIL of 77,6 % and 61,7 % (p<0,001) after RYGBP and GB respectively. RYGBP was associated with better food tolerance and greater improvement of the lipid profile. Conclusions: GB is associated with a smaller overall operative morbidity and similar major morbidity, but with more long-term complications, more reoperations, a significant number of reversal or conversion procedures, and reduced weight loss when compared with RYGBP. Five-year results of RYGBP are superior to GB and patients should be informed accordingly.

Bypass gastrique: prise en charge des complications et désagrements alimentaires [Gastric bypass: management of complications and food tolerance]

La chirurgie bariatrique est le seul traitement qui permette une perte pondérale significative sur le long terme mais le succès d'une telle intervention repose avant tout dans une sélection et une préparation attentive du patient. Une bonne connaissance des implications de l'opération permet de favoriser un changement de comportement alimentaire et par là aussi de diminuer les complications et les désagréments alimentaires. L'éducation du patient n'a de sens que si elle s'inscrit dans une prise en charge pluridisciplinaire, comprenant également un suivi diététique, planifié sur le long terme. La mastication, la vitesse d'ingestion des aliments, le fait de renoncer aux boissons gazeuses et de devoir boire régulièrement entre les repas, sont les éléments les plus difficiles à mettre en place pour le patient. Bariatric surgery is the only treatment inducing effective weight loss on the long term. The success of such an intervention is possible by carefully selecting and educating the candidates. Good understanding of the bariatric surgery implications allows the patients to modify their eating habits and thus decrease complications and food intolerance. Therefore patient education requires a multidisciplinary approach which implies the follow-up of a dietician on the long term. Mastication, speed of food ingestion, avoidance of carbonated beverages as well as the obligation to drink at frequent and regular intervals are the most difficult aspects to be taught to the patients

Reduction of ARNT in myeloid cells causes immune suppression and delayed wound healing.

Aryl hydrocarbon receptor nuclear translocator (ARNT) is a transcription factor that binds to partners to mediate responses to environmental signals. To investigate its role in the innate immune system, floxed ARNT mice were bred with lysozyme M-Cre recombinase animals to generate lysozyme M-ARNT (LAR) mice with reduced ARNT expression. Myeloid cells of LAR mice had altered mRNA expression and delayed wound healing. Interestingly, when the animals were rendered diabetic, the difference in wound healing between the LAR mice and their littermate controls was no longer present, suggesting that decreased myeloid cell ARNT function may be an important factor in impaired wound healing in diabetes. Deferoxamine (DFO) improves wound healing by increasing hypoxia-inducible factors, which require ARNT for function. DFO was not effective in wounds of LAR mice, again suggesting that myeloid cells are important for normal wound healing and for the full benefit of DFO. These findings suggest that myeloid ARNT is important for immune function and wound healing. Increasing ARNT and, more specifically, myeloid ARNT may be a therapeutic strategy to improve wound healing.

Influence of triamcinolone intravitreal injection on retinochoroidal healing processes.

To analyze the effects of triamcinolone intravitreal injection on the wound healing processes after argon laser retinal photocoagulation, wild type C57BL/6J mice, 8-12 weeks old underwent a standard argon laser photocoagulation protocol. After pentobarbital anesthesia and pupil dilatation, argon laser lesions were induced (50microm, 400mW, 0.05s). Two photocoagulation impacts created two disc diameters from the optic nerve in both eyes. The photocoagulated mice were divided into four groups: Group I (n=12), photocoagulation controls, did not receive any intravitreous injection. Group II (n=12), received an intravitreous injection of 1microl of balanced salt solution (BSS). Group III (n=12), received an intravitreous injection of 1microl containing 15microg of triamcinolone acetonide (TAAC) in BSS. Two mice from each of these three groups were sacrificed at 1, 3, 7, 14 days and 2 and 4 months after photocoagulation. Group IV (n=10) received 1.5, 3, 7.5, 15, or 30microg of TAAC and were all sacrificed on day 14. The enucleated eyes were subjected to systematic analysis of the cellular remodeling processes taking place within the laser lesion and its vicinity. To this purpose, specific antibodies against GFAP, von Willebrand factor, F4/80 and KI67 were used for the detection of astrocytes, activated Müller cells, vascular endothelial cells, infiltrating inflammatory cells and actively proliferating cells. TUNEL reaction was also carried out along with nuclear DAPI staining. Temporal and spatial observations of the created photocoagulation lesions demonstrate that 24h following the argon laser beam, a localized and well-delineated affection of the RPE cells and choroid is observed in mice in Groups I and II. The inner retinal layers in these mice eyes are preserved while TUNEL positive (apoptotic) cells are observed at the retinal outer nuclear layer level. At this stage, intense staining with GFAP is associated with activated retinal astrocytes and Müller cells throughout the laser path. From day 3 after photocoagulation, dilated new choroidal capillaries are detected on the edges of the laser lesion. These processes are accompanied by infiltration of inflammatory cells and the presence of proliferating cells within the lesion site. Mice in Group III treated with 15microg/mul of triamcinolone showed a decreased number of infiltrating inflammatory cells and proliferating cells, which was not statistically significant compared to uninjected laser treated controls. The development of new choroidal capillaries on the edges of the laser lesion was also inhibited during the first 2 months after photocoagulation. However, on month 4 the growth of new vessels was observed in these mice treated with TAAC. Mice of Group IV did not show any development of new capillaries even with small doses. After argon laser photocoagulation of the mouse eye, intravitreal injection of triamcinolone markedly influenced the retina and choroid remodeling and healing processes. Triamcinolone is a powerful inhibitor of the formation of neovessels in this model. However, this inhibition is transient. These observations should provide a practical insight for the mode of TAAC use in patients with wet AMD.

Improved Surgical Technique Reduces Complications at the Gastro-jejunostomy After Laparoscopic Roux-en-Y Gastric Bypass

Introduction: Roux-en-Y gastric bypass (RYGBP) is one of the commonest procedure for morbid obesity. It is associated with effective long-term weight loss, but can lead to significant complications, especially at the gastrojejunostomy (GJS) Patients and Methods: All the patients undergoing laparoscopic RYGBP at one of our two institutions were included in this study, in which we compared two different techniques for the construction of the GJS and their effects on the incidence of complications. In group A, anatomosis was performed on the posterior aspect of the gastric pouch. In group B it was performed across the staple line used to form the gastric pouch. A 21-mm circular stapler was used in all patients. Results: A total of 1128 patients were included between June 1999 and September 2009, 639 in group A and 488 in group B. Sixty patients developed a total of 65 complications at the GJS, with 14 (1,2 %) leaks, 42 (3,7 %) stricture, and 9 (0,8 %) marginal ulcers. Leaks (0,2 versus 2 %, p=0,005) and strictures (0,8 versus 5,9%, p<0,0001) were significantly fewer in group B than in group A. Conclusions: Improved surgical technique, with the GJS across the staple line used to form the gastric pouch, significantly reduces the rate of anastomotic complications at the GJS. A circular 21-mm stapler can be used with a low complication rate, and especially a low stricture rate. Additional methods to limit complications at the GJS are probably not routinely warranted.

Caveolin expression changes in the neurovascular unit after juvenile traumatic brain injury: signs of blood-brain barrier healing?

Traumatic brain injury (TBI) is one of the major causes of death and disability in pediatrics, and results in a complex cascade of events including the disruption of the blood-brain barrier (BBB). A controlled-cortical impact on post-natal 17 day-old rats induced BBB disruption by IgG extravasation from 1 to 3 days after injury and returned to normal at day 7. In parallel, we characterized the expression of three caveolin isoforms, cav-1, cav-2 and cav-3. While cav-1 and cav-2 are expressed on endothelial cells, both cav-1 and cav-3 were found to be present on reactive astrocytes, in vivo and in vitro. Following TBI, cav-1 expression was increased in blood vessels at 1 and 7 days in the perilesional cortex. An increase of vascular cav-2 expression was observed 7 days after TBI. In contrast, astrocytic cav-3 expression decreased 3 and 7 days after TBI. Activation of eNOS (via its phosphorylation) was detected 1 day after TBI and phospho-eNOS was detected both in association with blood vessels and with astrocytes. The molecular changes involving caveolins occurring in endothelial cells following juvenile-TBI might participate, independently of eNOS activation, to a mechanism of BBB repair while, they might subserve other undefined roles in astrocytes.