Intraoperative assessment of vascular access.

PURPOSE: The intraoperative quality assessment of the arteriovenous fistula for hemodialysis is an essential process to limit early failure due to technical problems or inadequate vascular quality. This step is not clearly defined in the literature with no recommendations. METHODS: We selected published articles related to the topic of intraoperative quality control of the vascular access for hemodialysis. RESULTS: The intraoperative blood flow measurement greater than 120 ml/min in autologous fistula and less than 320 ml/min in arteriovenous graft was described as predictive factors for early failure. CONCLUSIONS: The blood flow measurement should be performed after the confection of the anastomosis. When blood flow is limited, fistulography is an essential step to assess patency.

Physiological function of PARbZip circadian clock-controlled transcription factors.

PARbZip proteins (proline and acidic amino acid-rich basic leucine zipper) represent a subfamily of circadian transcription factors belonging to the bZip family. They are transcriptionally controlled by the circadian molecular oscillator and are suspected to accomplish output functions of the clock. In turn, PARbZip proteins control expression of genes coding for enzymes involved in metabolism, but also expression of transcription factors which control the expression of these enzymes. For example, these transcription factors control vitamin B6 metabolism, which influences neurotransmitter homeostasis in the brain, and loss of PARbZip function leads to spontaneous and sound-induced epilepsy that are frequently lethal. In liver, kidney, and small intestine, PAR bZip transcription factors regulate phase I, II, and III detoxifying enzymes in addition to the constitutive androstane receptor (CAR), one of the principal sensors of xenobiotics. Indeed, knockout mice for the three PARbZip transcription factors are deficient in xenobiotic detoxification and display high morbidity, high mortality, and accelerated aging. Finally, less than 20% of these animals reach an age of 1 year. Accumulated evidences suggest that PARbZip transcription factors play a role of relay, coupling circadian metabolism of xenobiotic and probably endobiotic substances to the core clock circuitry of local circadian oscillators.

Allergen-specific antibody and cytokine responses, mast cell reactivity and intestinal permeability upon oral challenge of sensitized and tolerized mice.

BACKGROUND: Food allergy has reached an epidemic level in westernized countries and although central mechanisms have been described, the variability associated with genetic diversity underscores the still unresolved complexity of these disorders. OBJECTIVE: To develop models of food allergy and oral tolerance, both strictly induced by the intestinal route, and to compare antigen-specific responses. METHODS: BALB/c mice were mucosally sensitized to ovalbumin (OVA) in the presence of the mucosal adjuvant cholera toxin, or tolerized by intra-gastric administrations of OVA alone. Antibody titres and cytokines were determined by ELISA, and allergic status was determined through several physiologic parameters including decline in temperature, diarrhoea, mast cell degranulation and intestinal permeability. RESULTS: OVA-specific antibodies (IgE, IgGs and IgA in serum and feces) were produced in sensitized mice exclusively. Upon intra-gastric challenge with OVA, sensitized mice developed anaphylactic reactions associated with a decline of temperature, diarrhoea, degranulation of mast cells, which were only moderately recruited in the small intestine, and increased intestinal permeability. Cytokines produced by immune cells from sensitized mice included T-helper type 2 cytokines (IL-5, IL-13), but also IL-10, IFN-gamma and IL-17. In contrast, all markers of allergy were totally absent in tolerized animals, and yet the latter were protected from subsequent sensitization, demonstrating that oral tolerance took place efficiently. CONCLUSION: This work allows for the first time an appropriate comparison between sensitized and tolerized BALB/c mice towards OVA. It highlights important differences from other models of allergy, and thus questions some of the generally accepted notions of allergic reactions, such as the protective role of IFN-gamma, the importance of antigen-specific secretory IgA and the role of mucosal mast cells in intestinal anaphylaxis. In addition, it suggests that IL-17 might be an effector cytokine in food allergy. Finally, it demonstrates that intestinal permeability towards the allergen is increased during challenge.

Acute ulcerative jejunal diverticulitis: case report of an uncommon entity.

Jejunal diverticulosis is a rare entity with variable clinical and anatomical presentations. Its reported incidence varies from 0.05% to 6%. Although there is no consensus on the management of asymptomatic jejunal diverticular disease, some complications are potentially life threatening and require early surgical treatment. We report a case of an 88-year-old man investigated for acute abdominal pain with a high biological inflammatory syndrome. Inflammation of multiple giant jejunal diverticulum was discovered at abdominal computed tomography (CT). As a result of the clinical and biological signs of early peritonitis, an emergency surgical exploration was performed. The first jejunal loop showed clear signs of jejunal diverticulitis. Primary segmental jejunum resection with end-to-end anastomosis was performed. Histopathology report confirmed an ulcerative jejunal diverticulitis with imminent perforation and acute local peritonitis. The patient made an excellent rapid postoperative recovery. Jejunal diverticulum is rare but may cause serious complications. It should be considered a possible etiology of acute abdomen, especially in elderly patients with unusual symptomatology. Abdominal CT is the diagnostic tool of choice. The best treatment is emergency surgical management.

Antigen-secretory IgA immune complexes are retro-transported into mouse Peyer's patches: immunotargeting to dendritic cells

RÉSUMÉ Les plaques de Peyer (PP) représentent le site d'entrée majeur des pathogènes au niveau des muqueuses intestinales. Après avoir traversé la cellule M, l'antigène est pris en charge par les cellules dendritiques (DC) de la région sub-épithéliale du dôme des PP. Ces dernières activent une réponse immunitaire qui conduit à la production de l'IgA de sécrétion (SIgA), l'anticorps majeur au niveau muqueux. Des études précédentes dans notre laboratoire ont démontré qu'après administration de SIgA dans des anses intestinales de souris, les SIgA se lient spécifiquement aux cellules M, entrent dans les PP, et sont éventuellement internalisées par les DC. Le but de ce travail est de comprendre la relevance biologique de l'entrée des SIgA dans les PP et leur relevance physiologique dans l'homéostasie mucosale. Dans un premier temps, nous avons montré en utilisant une méthode de purification optimisée basée sur une isolation magnétique, que, en plus des DC myéloïdes (CD11c+/CD11b+) et des DC lymphoïdes (CD11c+/CD8+), les PP de souris contiennent un nouveau sous-type de DC exprimant les marqueurs CD11c et CD19. L'utilisation de la microscopie confocale nous a permis de démontrer que les DC myéloïdes internalisent des SIgA, contrairement aux DC lymphoïdes qui n'interagissent pas avec les SIgA, alors que le nouveau sous-type de DC exprimant CD19 lie les SIgA. En plus, nous avons démontré qu'aucune des DC de rate, de ganglion bronchique ou de ganglion inguinal interagit avec les SIgA. Dans le but d'explorer si les SIgA peuvent délivrer des antigènes aux DC des PP in vivo, nous avons administré des complexes immunitaires formés de Shigella flexneri complexées à des SIgA, dans des anses intestinales de souris. Nous avons observé une entrée dans les PP, suivie d'une migration vers les ganglions mésentériques drainants, contrairement aux Shigella flexneri seules, qui n'infectent pas la souris par la voie intestinale. Shigella flexneri délivrée par SIgA n'induit pas de destruction tissulaire au niveau de l'intestin. En plus de l'exclusion immunitaire, ces résultats suggèrent un nouveau rôle des SIgA, qui consiste à transporter des antigènes à l'intérieur des PP dans un contexte non-inflammatoire. RÉSUMÉ DESTINÉ À UN LARGE PUBLIC L'intestin a pour rôle principal d'absorber les nutriments digérés tout au long du tube digestif, et de les faire passer dans le compartiment intérieur sanguin. Du fait de son exposition chronique avec un monde extérieur constitué d'aliments et de bactéries, l'intestin est un endroit susceptible aux infections et a donc besoin d'empêcher l'entrée de microbes. Pour cela, l'intestin est tapissé de "casernes" appelées les plaques de Peyer, qui appartiennent à un système de défense appelé système immunitaire muqueux. Les plaques de Peyer sont composées de différents types de cellules, ayant pour rôle de contrôler l'entrée de microbes et de développer une réaction immunitaire lors d'infection. Cette réaction immunitaire contre les microbes (antigènes) débute par la prise en charge de l'antigène par des sentinelles, les cellules dendritiques. L'antigène est préparé de façon à être reconnu par d'autres cellules appelées lymphocytes T capables d'activer d'autres cellules, les lymphocytes B. La réaction immunitaire résulte dans la production par les lymphocytes B d'un anticorps spécifique appelé IgA de sécrétion (SIgA) au niveau de la lumière intestinale. De manière classique, le rôle de SIgA au niveau de la lumière intestinale consiste à enrober les microbes et donc exclure leur entrée dans le compartiment intérieur. Dans ce travail, nous avons découvert une nouvelle fonction des SIgA qui consiste à introduire des antigènes dans les plaques de Peyer, et de les diriger vers les cellules dendritiques. Sachant que les SIgA sont des anticorps qui ne déclenchent pas de réactions de défense violentes dites inflammatoires, l'entrée des antigènes via SIgA serait en faveur d'une défense intestinale maîtrisée sans qu'il y ait d'inflammation délétère. Ces résultats nous laissent supposer que l'entrée d'antigènes via SIgA pourrait conduire le système immunitaire muqueux à reconnaître ces antigènes de manière appropriée. Ce mécanisme pourrait expliquer les désordres immunitaires de types allergiques et maladies auto-immunitaires que l'on rencontre chez certaines personnes déficientes en IgA, chez qui cette lecture d'antigènes de manière correcte serait inadéquate. ABSTRACT Peyer's patches (PP) represent the primary site for uptake and presentation of ingested antigens in the intestine. Antigens are sampled by M cells, which pass them to underlying antigen-presenting cells including dendritic cells (DC). This leads to the induction of mucosal T cell response that is important for the production of secretory IgA (SIgA), the chief antibody at mucosal surfaces. Previous studies in the laboratory have shown that exogenous SIgA administrated into mouse intestinal loop binds specifically to M cells, enter into PP, and is eventually internalized by DC. The aim of this work is to understand the biological significance of the SIgA uptake by PP DC and its physiological relevance for mucosal homeostasis. As a first step, we have shown by using an optimized MACS method that, in addition to the CD11c+/CD11b+ (myeloid DC) and CD11c+/CD8+ (lymphoid DC) subtypes, mouse PP contain a novel DC subtype exhibiting both CD11c and CD19 markers. By using a combination of MACS isolation and confocal microscopy, we have demonstrated that in contrast to the lymphoid DC which do not interact with SIgA, the myeloid DC internalize SIgA, while the CD19+ subtype binds SIgA on its surface. Neither spleen DC, nor bronchial-lymph node DC, nor inguinal lymph node DC exhibit such a binding specificity. To test whether SIgA could deliver antigens to PP DC in vivo, we administered SIgA-Shigella flexneri immune complexes into mouse intestinal loop containing a PP. We found that (i) SIgA-Shigella flexneri immune complexes enter the PP and are internalized by sub-epithelial dome PP DC, in contrast to Shigella flexneri alone that does not penetrate the intestinal epithelia in mice, (ii) immune complexes migrate to the draining mesenteric lymph node, (iii) Shigella flexneri carried via SIgA do not induce intestinal tissue destruction. Our results suggest that in addition to immune exclusion, SIgA transports antigens back to the PP under non-inflammatory conditions.

Sensate lateral arm flap for defects of the lower leg.

Ideally, reconstruction of lower extremity soft tissue defects includes not only an esthetically pleasing 3-dimensional shape and solid anchoring to the underlying structures to resist shear forces, but should also address the restoration of sensation. Therefore, we present a prospective study on defect reconstruction of the lower leg and ankle to evaluate the role of sensate free fasciocutaneous lateral arm flap and the impact of sensory nerve reconstruction. Thirty patients were allocated randomly to the study group (n = 15) that obtained end-to-side sensate coaptation using the lower lateral cutaneous brachial nerve to the tibial nerve using the epineural window technique, or to the control group reconstructed without nerve coaptation. At 1-year follow-up the patients were evaluated for pain sensation, thermal sensibility, static and moving 2-point discrimination, and Semmes-Weinstein monofilament tests. Data from both groups were compared and statistically analyzed with the Mann-Whitney U test and the Fisher exact test. Flaps of the study group reached a static and moving 2-point discrimination and Semmes-Weinstein monofilament tests nearly equal to the contralateral leg area and significantly better than flaps of the control group. Donor damage morbidity of the tibial nerve did not occur. To our point of view resensation should be carried out by end-to-side neurorrhaphy to the tibial nerve because of the superior restoration of sensibility.

The Four Different Types of Internal Hernia Occurring After Laparascopic Roux-en-Y Gastric Bypass Performed for Morbid Obesity: Are There Any Multidetector Computed Tomography (MDCT) Features Permitting Their Distinction?

BACKGROUND: Four different types of internal hernias (IH) are known to occur after laparoscopic Roux-en-Y gastric bypass (LRYGBP) performed for morbid obesity. We evaluate multidetector row helical computed tomography (MDCT) features for their differentiation. METHODS: From a prospectively collected database including 349 patients with LRYGBP, 34 acutely symptomatic patients (28 women, mean age 32.6), operated on for IH immediately after undergoing MDCT, were selected. Surgery confirmed 4 (11.6%) patients with transmesocolic, 10 (29.4%) with Petersen's, 15 (44.2%) with mesojejunal, and 5 (14.8%) with jejunojejunal IH. In consensus, 2 radiologists analyzed 13 MDCT features to distinguish the four types of IH. Statistical significance was calculated (p < 0.05, Fisher's exact test, chi-square test). RESULTS: MDCT features of small bowel obstruction (SBO) (n = 25, 73.5%), volvulus (n = 22, 64.7%), or a cluster of small bowel loops (SBL) (n = 27, 79.4%) were inconsistently present and overlapped between the four IH. The following features allowed for IH differentiation: left upper quadrant clustered small bowel loops (p < 0.0001) and a mesocolic hernial orifice (p = 0.0003) suggested transmesocolic IH. SBL abutting onto the left abdominal wall (p = 0.0021) and left abdominal shift of the superior mesenteric vessels (SMV) (p = 0.0045) suggested Petersen's hernia. The SMV predominantly shifted towards the right anterior abdominal wall in mesojejunal hernia (p = 0.0033). Location of the hernial orifice near the distal anastomosis (p = 0.0431) and jejunojejunal suture widening (p = 0.0005) indicated jejunojejunal hernia. CONCLUSIONS: None of the four IH seems associated with a higher risk of SBO. Certain MDCT features, such as the position of clustered SBL and hernial orifice, help distinguish between the four IH and may permit straightforward surgery.

Superior vena cava syndrome caused by invasive epidermoid carcinoma.

Lung cancer is the most frequent cause of superior vena cava (SVC) syndrome. Malignant SVC syndrome is generally considered a contraindication to curative resection, although palliative bypasses are done for symptoms that do not respond to medical therapy. However, a majority of patients with such advanced disease die of complications caused by the primary tumor rather than distant metastasis. We present the case of one patient with lung cancer invading the mediastinal structures. Combined resection and replacement of the SVC with a segment of Dacron vascular graft was performed. Postoperative survival time was 24 months.

Role of transcription factor PROX1 in colon cancer metastasis

Initiation and progression of most colorectal cancers (CRCs) are driven by hyper-activation of the canonical Wnt/ß-catenin/TCF signaling pathway. However, a basal level of activation of this pathway is necessary for intestinal cell homeostasis; thus only CRC-specific effectors of this pathway could be exploited as potential clinical targets. PROX1 is an evolutionary conserved transcription factor with multiple roles in several tissues in embryogenesis, and increasing relevance in cancer. PROX1 is a colon cancer-specific Wnt target in the intestine, thus it might represent a therapeutic target. The role of PROX1 in promoting the transition from early to highly-dysplastic adenoma was previously described [1], Importantly, tumor metastasis is a leading cause of cancer-related mortality. Frequently, micrometastases are already present in patients at the time of diagnosis, therefore better understanding of the mechanisms regulating growth of macrometastatic lesions is important for the development of novel treatment approaches. In this study we showed that PROX1 is expressed in colon cancer stem cell and promotes the outgrowth of metastatic lesions. Firstly, we analyzed the expression of PROX1 in advanced CRCs and their metastases. We found that PROX1 over-expression is a feature of microsatellite stable tumors (~85% of microsatellite stable (MSS) CRCs), which generally have worse prognosis in comparison to microsatellite unstable CRCs. Analysis of primary CRCs and corresponding metastatic lesions showed that PROX1 expression is conserved, or increased in metastases. Further bioinformatics analysis of tumor and metastases gene expression profiles showed that PROX1 is co- expressed with stem cell and progenitor markers. Moreover, in inducible ApcmLgr5-EGFP-lres-CreERT2 model, Prox1+ cells marked a sub-population of Lgr5+ stem cells and subsequent transient amplifying cell population. Orthotopic model of CRC and lung colonization assays in mice demonstrated that PROX1 promotes tumor cell outgrowth in metastatic lesions, while it has no effect on primary tumor growth, invasion, and survival in circulation or cell extravasation. In vitro, PROX1 expressing tumor cells demonstrated strongly increased capacity to form spheroids, and increased survival and proliferation under hypoxic or nutrient-deprivation conditions. By monitoring cellular respiration under these conditions, we found that PROX1 expressing cells exhibit a better metabolic adaptation to changes in fuel source. Autophagy inhibitors, prevented growth both in vitro and in vivo of PROX1 expressing cells. Importantly, conditional inactivation of PROX1 after the establishment of metastases prevented further growth of macroscopic lesions resulting in stable disease. In summary, we identified a novel mechanism underlying the ability of metastatic colon cancer stem and progenitor cells to survive and grow in target organs through metabolic adaptation. Our results establish PROX1 as a key factor of CRC metastatic disease where it promotes survival of metastatic colon cancer stem-like cells, through their metabolic adaptation in sub-optimal microenvironments - L'initiation et la progression de la plupart des cancers colorectaux (CRC) sont entraînées par une hyper-activation de la voie métabolique Wnt/ß- caténine/TCF. Toutefois, un niveau d'activation minimal de Wnt est nécessaire pour l'homéostasie des cellules intestinales ; ainsi seuls des effecteurs spécifiques du CRC- de cette voie pourraient être exploités comme des cibles cliniques potentielles. PROX1 est un facteur de transcription évolutif conservé avec de multiples rôles dans plusieurs tissus durant l'embryogenèse et une pertinence croissante dans le cancer. PROX1 est une cible Wnt spécifique dans le cancer de l'intestin, donc il pourrait représenter une cible thérapeutique. Le rôle de PROX1 durant l'évolution de la maladie d'un stade précoce jusqu'à l'adénome hautement dysplasique a été décrit précédemment. Surtout, la métastase des tumeurs est une cause majeure de mortalité liée au cancer. Souvent, les micro-métastases sont déjà présentes chez les patients au moment du diagnostic, c'est pourquoi une meilleure compréhension des mécanismes régulant la croissance des lésions macrométastatiques est importante pour le développement de nouvelles approches thérapeutiques. Dans cette étude, nous avons prouvé que PROX1 est exprimé dans les cellules souches du cancer du côlon et favorise l'apparition de lésions métastatiques. Nous avons d'abord analysé l'expression de PROX1 dans des CRC avancés ainsi que dans leurs métastases. Nous avons constaté que la surexpression de PROX1 est une caractéristique des tumeurs stables microsatellites (~85% du MSS CRC), qui ont généralement un pronostic défavorable par rapport aux microsatellites CRC instables. L'analyse des CRC primaires et de leurs métastases liées a montré que l'expression de PROX1 est conservée, voire augmentée dans les métastases. A l'aide d'une base de données de tumeurs et métastases, nous avons observé une co- régulation de PROX1 entre cellules souches et marqueurs de progéniteurs mais pas avec des cellules différenciées. De plus, en utilisant un modèle Apcm Lgr5-EGFP-IRES-CreERT2 inductible, les cellules Prox1+ ont marqué une sous-population de cellules LGR& capable de produire une lignée. Un modèle orthotopique de cancer colorectal et des essais de colonisation du poumon chez la souris ont démontré que PROX1 favorise l'excroissance des cellules tumorales dans les lésions métastatiques, alors qu'il n'a aucun effet sur la croissance tumorale primaire, l'invasion ou une extravasation des cellules. In vitro, les cellules tumorales exprimant PROX1 ont démontré une forte augmentation de leur capacité à former des sphéroïdes, ainsi qu'une augmentation de la survie et de la prolifération dans des conditions hypoxiques ou lors de privation de nutriments. En contrôlant la respiration cellulaire dans ces conditions, nous avons constaté que les cellules exprimant PROX1 présentent une meilleure adaptation métabolique à l'évolution des sources de carburant. Des inhibiteurs de l'autophagie, suggérant une approche thérapeutique potentielle, ont tué à la fois in vitro et in vivo les cellules exprimant PROX1. Surtout, l'inactivation conditionnelle de PROX1 après l'apparition de métastases a empêché la croissance des lésions macroscopiques résultant en une maladie stable. En résumé, nous avons identifié un nouveau mécanisme mettant en évidence la capacité des cellules souches du cancer du côlon métastatique à survivre et à se développer dans les organes cibles grâce à l'adaptation métabolique. Nos résultats définissent PROX1 comme un facteur clé du cancer colorectal métastatique en favorisant la survie des cellules souches métastatiques apparentées au cancer du colon grâce à leur adaptation métabolique aux microenvironnements défavorables.

A simplified method of stabilization and hemostasis for minimally invasive coronary artery bypass.

We describe a simple method to achieve both hemostasis and stabilization of the left anterior descending coronary artery during minimally invasive coronary artery bypass grafting. This technique allows the surgeon to perform a precise anastomosis of the left internal mammary artery to the target vessel on a beating heart.

Diagnosis and workup of 522 consecutive patients with neuroendocrine neoplasms in Switzerland.

BACKGROUND: Neuroendocrine neoplasms (NENs) are difficult to diagnose. We used SwissNET data to characterise NEN patients followed in the two academic centres of western Switzerland (WS), and to compare them with patients followed in eastern Switzerland (ES) as well as with international guidelines. METHOD: SwissNET is a prospective database covering data from 522 consecutive patients (285 men, 237 women) from WS (n = 99) and ES (n = 423). RESULTS: Mean ± SD age at diagnosis was 59.0 ± 15.7 years. Overall, 76/522 experienced a functional syndrome, with a median interval of 1.0 (IQR: 1.0-3.0) year between symptoms onset and diagnosis. A total of 51/522 of these tumours were incidental. The primary tumour site was the small intestine (29%), pancreas (21%), appendix (18%) and lung (11%) in both regions combined. In all, 513 functional imaging studies were obtained (139 in WS, 374 in ES). Of these, 381 were 111In-pentetreotide scintigraphies and 20 were 68Ga-DOTATOC PET. First line therapy was surgery in 87% of patients, medical therapy (biotherapy or chemotherapy) in 9% and irradiation in 3% for both regions together. CONCLUSION: Swiss NEN patients appear similar to what has been described in the literature. Imaging by somatostatin receptor scintigraphy (SRS) is widely used in both regions of Switzerland. In good accordance with published guidelines, data on first line therapy demonstrate the crucial role of surgery. The low incidence of biotherapy suggests that long-acting somatostatin analogues are not yet widely used for their anti-proliferative effects. The SwissNET initiative should help improve compliance with ENETS guidelines in the workup and care of NEN patients.

High incidence of childhood hemolytic uremic syndrome in Switzerland is associated with indicators of livestock farming intensity

Background: Hemolytic-uremic syndrome (HUS) is a multisystem disorder associated with significant morbidity and mortality. Typically, HUS is preceded by an episode of (bloody) diarrhea mostly due to Shiga-toxin (Stx) producing Escherichia coli (STEC). The main reservoir for STEC is the intestine of healthy ruminants, mostly cattle, and recent studies have revealed an association between indicators of livestock density and human STEC infection or HUS, respectively. Nationwide data on HUS in Switzerland have been established through the Swiss Pediatric Surveillance Unit (SPSU) [Schifferli et al. Eur J Pediatr. 2010; 169:591-8]. Aims: Analysis of age-specific incidence rate of childhood HUS and possible association of Shiga-toxin associated HUS (Stx-HUS) with indicators of livestock farming intensity. Methods: Epidemiological and ecological analysis based on the SPSU data (1997-2003) and the database of the Swiss Federal Statistical Office (data on population and agriculture). Results: One hundred-fourteen cases were registered, 88% were ≤5 years old. The overall annual incidence rate was 1.42 (0.60-1.91) and 4.23 (1.76-6.19) per 100000 children ≤5 and ≤16 years, respectively (P = 0.005). Stx-HUS was more frequent compared to cases not associated with STEC (P = 0.002). The incidence rate for Stx-HUS was 3.85 (1.76-5.65) in children ≤5, compared to 0.27 (0.00-0.54) per 100'000 children 5-16 years (P = 0.002), respectively. The incidence rate of cases not associated with STEC infection did not significantly vary with age (P = 0.107). Compared to data from Scotland, Canada, Ireland, Germany, England, Australia, Italy, and Austria the annual incidence rate of HUS in young children is highest in Switzerland. Ecological analysis revealed strong association between the incidence rate of Stx-HUS and indicators of rural occupation (agricultural labourer / population, P = 0.030), farming intensity (livestock breeding farms / population, P = 0.027) and cattle density (cattle / cultivated area, P = 0.013). Conclusions: Alike in other countries, HUS in Switzerland is mostly associated with STEC infection and affects predominantly young children. However, the incidence rate is higher compared to countries abroad and is significantly correlated with indicators of livestock farming intensity. The present data support the impact of direct and indirect contact with animals or fecal contaminants in transmission of STEC to humans.

Cricotracheal resection for laryngeal invasion by thyroid carcinoma: our experience.

Invasion of the laryngeal framework by thyroid carcinoma requires specific surgical techniques and carries a higher rate of complications that deserve to be highlighted. We reviewed our data from 1995 to 2012 and found six patients with laryngotracheal invasion by thyroid carcinoma. All underwent total thyroidectomy and single-stage cricotracheal resection, plus anterolateral neck dissection. Three had airway obstruction that necessitated prior endoscopic debulking. None of the patients needed a tracheotomy. There were four cases of papillary carcinoma, and two cases of undifferentiated carcinoma. One patient died of complications of the procedure (anastomotic dehiscence and tracheo-innominate artery fistula). Another died 2 months after the procedure from local recurrence and aspiration pneumonia. One case presented recurrence at 15 months, which was managed by re-excision and adjuvant radiotherapy; after 26 months of follow-up, he has no evidence of locoregional recurrence. The three other patients are alive without evidence of disease at 6, 18 and 41 months, respectively. Cricotracheal resection for subglottic invasion by thyroid carcinoma is an effective procedure, but carries significant risks of complications. This could be attributed to the devascularisation of the tracheal wall due to the simultaneous neck dissection, sacrifice of the strap muscles or of a patch of oesophageal muscle layer. We advocate a sternocleidomastoid flap to cover the anastomosis. Cricotracheal resection for subglottic invasion can be curative with good functional outcomes, even for the advanced stages of thyroid cancer. Endoscopic debulking of the airway prior to the procedure avoids tracheotomy.

Lésions iatrogènes des voies biliaires lors de la cholécystectomie laparoscopique

Objective: Laparoscopic cholecystectomy (LC) has become the gold standard in the treatment of symptomatic cholelithiasis. The aim of this study was to determine the frequency of occurrence and risk factors of iatrogenic bile duct injuries (IBDI) in the LC and study their treatment modalities. Methods: Between January 2000 and December 2011, a series of 13 patients (6 men, 7 women, mean age 66.7 years, mean BMI 27.9 kg/m2) underwent IBDI in our institution for 2'840 LC performed. These patients were identified retrospectively using a wide range of classification codes in our medical center for archiving. Their medical records were examined individually to identify a IBDI. Results: The frequency of IBDI was 0.46% (n=13). The most common indication for surgery was acute cholecystitis (69.2%). The main cause was the confusion of the common bile duct with the cystic duct in 38.5% of cases. Strasberg classification applied to our sample identified the following injuries: A (n=4), D (n=4), E1 (n=3) and E5 (n=2). They were diagnosed intraoperatively in 46.2% of cases and postoperatively in 53.8% of cases. The rate of type D lesions was significantly higher in the group with intraoperative recognition (p= 0.009), while the rate of type A lesions was significantly higher in the group with postoprative recognition (p = 0.026). Intraoperatively, 83.3% of the lesions were treated by primary suture with a biliary drainage and a hepatico-jejunal anastomosis was performed immediately in one case (16.7%). Postoperatively, 85.7% of the lesions were treated by non-surgical techniques in first- line and 4 of them have undergone biliary surgery later. The total number of therapeutic procedures for each IBDI after LC was significantly higher when the diagnosis was made postoperatively (3.4 vs. 1.5, p= 0.040). Conclusion: This study has identified a patient at risk of IBDI, this one is relatively old, overweight and has an inflammatory environment. Misidentification of biliary anatomy remains the main cause. There is a clear relationship between the timing of recognition and the type of injury involved. The primary suture with adequate drainage seems to be the method of choice for intraoperative discovery, while in case of postoperative recognition, the treatment must be adapted after a multidisciplinary consensus by combining interventional radiology, endoscopy and surgery.

A 338-bp proximal fragment of the glucose transporter type 2 (GLUT2) promoter drives reporter gene expression in the pancreatic islets of transgenic mice.

The high Km glucose transporter GLUT2 is a membrane protein expressed in tissues involved in maintaining glucose homeostasis, and in cells where glucose-sensing is necessary. In many experimental models of diabetes, GLUT2 gene expression is decreased in pancreatic beta-cells, which could lead to a loss of glucose-induced insulin secretion. In order to identify factors involved in pancreatic beta-cell specific expression of GLUT2, we have recently cloned the murine GLUT2 promoter and identified cis-elements within the 338-bp of the proximal promoter capable of binding islet-specific trans-acting factors. Furthermore, in transient transfection studies, this 338-bp fragment could efficiently drive the expression of the chloramphenicol acetyl transferase (CAT) gene in cell lines derived from the endocrine pancreas, but displayed no promoter activity in non-pancreatic cells. In this report, we tested the cell-specific expression of a CAT reporter gene driven by a short (338 bp) and a larger (1311 bp) fragment of the GLUT2 promoter in transgenic mice. We generated ten transgenic lines that integrated one of the constructs. CAT mRNA expression in transgenic tissues was assessed using the RNAse protection assay and the quantitative reverse transcribed polymerase chain reaction (RT-PCR). Overall CAT mRNA expression for both constructs was low compared to endogenous GLUT2 mRNA levels but the reporter transcript could be detected in all animals in the pancreatic islets and the liver, and in a few transgenic lines in the kidney and the small intestine. The CAT protein was also present in Langerhans islets and in the liver for both constructs by immunocytochemistry. These findings suggest that the proximal 338 bp of the murine GLUT2 promoter contain cis-elements required for the islet-specific expression of GLUT2.