Familial occurrence of an association of multiple intestinal atresia and choanal atresia: a new syndrome?

We report on two familial cases from a non-consanguineous marriage, presenting multiple intestinal and choanal atresia. Massive hydramnios and dilatation of the bowel were observed at 29 weeks of gestation during routine ultrasound scan of a healthy mother. The fetal karyotype was normal and cystic fibrosis screening was negative. Regular scans were performed throughout the pregnancy. The child was born at 34 weeks gestation. Choanal atresia was diagnosed at birth and abdominal investigations showed multiple atresia interesting both the small bowel and the colon. Further interventions were necessary because of recurrent obstructions. During the following pregnancy, a dilatation of the fetal intestinal tract was detected by ultrasonography at 27 weeks of gestation. Pregnancy was interrupted. Post-mortem examination of the fetus confirmed the stenosis of long segments of the small intestine associated with areas of colonic atresia. In both cases, histology and distribution were consistent with those reported in hereditary multiple intestinal atresia (HMIA). An association between multiple intestinal and choanal atresia has never been reported. We suggest it could correspond to a new autosomal recessive entity for which cytogenetic investigations and high-resolution array CGH revealed no visible anomalies.

Combined endoscopic-laparoscopic resection of colon polyps.

Aims: To analyze the current literature on combined endoscopic-laparoscopic resection of colon polyps and to compare this new approach to standard laparoscopic colonic resection for polyps not suitable for endoscopic resection. Results: Several studies demonstrated that with a combined endoscopic-laparoscopic approach, polyps were successfully resected in 82-91% with a low morbidity of 3-10% and a short hospital stay of 1-2 days. Segmental laparoscopic resection was necessary in only 9-12%, but had a conversion rate to open surgery of 15% with an average hospital stay of 6-11 days. A cancerous polyp was found in 6-13% after a combined approach, with lymph node metastasis in 6%. Recurrent polyps after a combined endoscopic-laparoscopic resection seem to be rare, but follow-up of most studies is short and incomplete. Conclusion: Combined endoscopic-laparoscopic resection of colon polyps is feasible, safe, and has a high success rate. Malignant lesions can be treated laparoscopically during the same operation, avoiding the need for a second procedure, and with good long-term oncologic outcome.

Systematic review of delayed postoperative hemorrhage after pancreatic resection

Objective:This review assesses the presentation,management, and outcome of delayed postpancreatectomy hemorrhage (PPH) and suggests a novel algorithm as possible standard of care.Methods: An electronic search of Medline and Embase databases from January 1990 to February 2010 was undertaken. A random-effect meta-analysis for success rate and mortality of laparotomy vs. interventional radiology after delayed PPH was performed.Results: Fifteen studies including 248 patients with delayed PPH were included. Its incidence was 3?3%. A sentinel bleed heralding a delayed PPH was observed in 45% of cases. Pancreatic leaks or intraabdominal abscesses were found in 62%. Interventional radiology was attempted in 41%, and laparotomy was undertaken in 49%. On meta-analysis comparing laparotomy vs. interventional radiology, no significant difference could be observed in term of complete hemostasis (76% vs. 80%; P = 0?35). A statistically significant difference favored interventional radiology vs. laparotomy in term of mortality (22% vs. 47%; P = 0?02).Conclusion: Proper and early management of postoperative complications, such as pancreatic leak and intraabdominal abscess, minimizes the risk of delayed PPH. Sentinel bleeding needs to be thoroughly investigated. If a pseudoaneurysm is detected, it has to be treated by interventional angiography, in order to prevent a further delayed PPH. Early angiography and embolization or stenting is safe and should be the procedure of choice. Surgery remains a therapeutic option if no interventional radiology is available, or patients cannot be resuscitated for an interventional treatment.

Enhanced-reality video fluorescence: a real-time assessment of intestinal viability.

OBJECTIVE: Our aim was to evaluate a fluorescence-based enhanced-reality system to assess intestinal viability in a laparoscopic mesenteric ischemia model. MATERIALS AND METHODS: A small bowel loop was exposed, and 3 to 4 mesenteric vessels were clipped in 6 pigs. Indocyanine green (ICG) was administered intravenously 15 minutes later. The bowel was illuminated with an incoherent light source laparoscope (D-light-P, KarlStorz). The ICG fluorescence signal was analyzed with Ad Hoc imaging software (VR-RENDER), which provides a digital perfusion cartography that was superimposed to the intraoperative laparoscopic image [augmented reality (AR) synthesis]. Five regions of interest (ROIs) were marked under AR guidance (1, 2a-2b, 3a-3b corresponding to the ischemic, marginal, and vascularized zones, respectively). One hour later, capillary blood samples were obtained by puncturing the bowel serosa at the identified ROIs and lactates were measured using the EDGE analyzer. A surgical biopsy of each intestinal ROI was sent for mitochondrial respiratory rate assessment and for metabolites quantification. RESULTS: Mean capillary lactate levels were 3.98 (SD = 1.91) versus 1.05 (SD = 0.46) versus 0.74 (SD = 0.34) mmol/L at ROI 1 versus 2a-2b (P = 0.0001) versus 3a-3b (P = 0.0001), respectively. Mean maximal mitochondrial respiratory rate was 104.4 (±21.58) pmolO2/second/mg at the ROI 1 versus 191.1 ± 14.48 (2b, P = 0.03) versus 180.4 ± 16.71 (3a, P = 0.02) versus 199.2 ± 25.21 (3b, P = 0.02). Alanine, choline, ethanolamine, glucose, lactate, myoinositol, phosphocholine, sylloinositol, and valine showed statistically significant different concentrations between ischemic and nonischemic segments. CONCLUSIONS: Fluorescence-based AR may effectively detect the boundary between the ischemic and the vascularized zones in this experimental model.

Unexpected bleeding following eyelid tumor resection leading to the rare diagnosis of acquired haemophilia.

BACKGROUND: Our goal is to report for the first time in the literature a case of uncontrolled bleeding after an oculoplastic surgical procedure leading to the diagnosis of acquired haemophilia. HISTORY AND SIGNS: An 82-year-old patient underwent tumor excision and reconstruction of his right lower eyelid. On the same day, uncontrolled bleeding occurred that resisted optimal blood pressure control, external compression, surgical haemostasis and wound revision. Usual coagulation screening tests were normal, except for a slightly prolonged activated partial thromboplastin time. THERAPY AND OUTCOME: Extensive coagulation check was performed, which showed a severely reduced factor VIII due to the presence of an inhibitor. The bleeding was immediately stopped after administration of recombinant factor VIIa. After healing of the wound, factor VIIa treatment was replaced by immunosuppressive therapy. The factor VIII inhibitor became unmeasurable and remained so for three months after stopping the immunosuppressive therapy. CONCLUSIONS: Ophthalmologists confronted with unexpected uncontrolled bleeding should think about the possibility of blood dyscrasia, in particular acquired haemophilia.

Extensive (8 to 12 cm2) noncircumferential endoscopic mucosal resection for early esophageal cancer.

Background: Endoscopic mucosal resection (EMR) is an appealing method for treating intramucosal esophageal cancer but must comply with the following stringent requirements: proper preoperative staging, complete resection of the lesion, obtaining a resected specimen for histologic analysis of safety margins, and squamous reepithelialization without stricture formation. Methods: A rigid esophagoscope was created to resect up to 12 cm(2) of esophageal mucosa in a single specimen and at a constant depth through the submucosa. Under visual control, the esophageal mucosa is sucked into a transparent window and resected with a thin diathermy wire loop in 10 seconds. After extensive preclinical studies in a sheep model, this article reports our early experience in humans. Results: Twenty-one hemi-circumferential EMRs were performed for 11 dysplastic Barrett's esophagi and 10 early squamous cell carcinomas with no perforation, one hemorrhage controlled by embolization of the left gastric artery, and one incomplete resection. Deep safety margins were clear in 19 of 21 resected specimens (2 patients, unfit for operations, had submucosal invasion of squamous cell carcinoma and adenocarcinoma, respectively). Lateral margins were not clear by definition in 7 circumferential Barrett's esophagi, but were clear in 4 incomplete Barrett's esophagi and 10 early squamous cell carcinomas. Conclusions: Large EMRs of 12 cm(2) can safely be performed at the submucosal level in the esophagus. Although feasible in one session, circumferential EMR in humans is not yet advisable because of the risk of stricture formation during the healing phase. The rate of complications of this series of 21 EMRs in humans is acceptable. (Ann Thorac Surg 2010; 89: S2151-5) (C) 2010 by The Society of Thoracic Surgeons

Role of pparß in irradiation mediated intestinal damage

Les récepteurs activés proliférateurs de peroxisomes (PPARs) appartiennent à la grande famille des récepteurs nucléaires et ont été impliqué dans plusieurs processus physiologiques. Parmi les trois isotypes PPAR, PPARβ est bien connu pour son rôle dans les décisions déterminant le destin des cellules, notamment dans les processus de prolifération, de différentiation et d'apoptose. Ce rôle a particulièrement été souligné comme protecteur dans les contextes de survie cellulaire et de cicatrisation. Il est fortement exprimé dans l'intestin grêle. Notre groupe a déjà rapporté sa présence importante dans les cryptes duodénales, où se trouvent les cellules souches intestinales. Précédemment, nous avons aussi fait remarquer le rôle de PPARβ dans la differentiation des cellules de Paneth, par la régulation négative de la signalisation Ihh de l'épithélium intestinal. Malgré sa capacité de figurer parmi les tissus du corps qui se régénèrent le plus rapidement, l'épithélium intestinal est particulièrement sensible aux attaques cytotoxiques, surtout celles dues à la radiothérapie des cancers abdomino-pelviens. Cela peut donner lieu à des lésions gastro-intestinal en tant qu'effet indésirable d'une exposition aiguë et chronique à l'irradiation. En raison du rôle protecteur de PPARβ le but de cette étude était de comprendre les voies de signalisation moléculaires régulées par PPARβ qui sont impliquées dans les réponses des cellules intestinales aux dommages causés par l'irradiation.Afin de déchiffrer les mécanismes moléculaires sous-jacents, un modèle in-vitro d'une lignée cellulaire - HT-29 a été utilisée. Il n'y a cependant pas de preuve d'un effet protecteur de PPARβ dans divers contextes d'endommagement cellulaire testés in-vitro. Ceci contraste avec les observations in-vivo qui indiquent que l'irradiation provoque une létalité supérieure dans les souris PPARβ-/- par rapport aux souris PPARβ+/+, entre autre correlée avec une apoptose augmentée des cellules souches intestinales à 4h après irradiation. En plus, le décès plus important de cellules mésenchymateuses a été observé dans les souris PPARβ-/-, 8 jours après irradiation. Moins nombreuses, ces cellules se sont également détachées de la matrice extracellulaire reliant l'épithélium et le mésenchyme. Nous stipulons qu'in-vivo, PPARβ participe au dialogue entre le mésenchyme et l'épithélium, ce qui est concordant avec le délai observé lors de la réparation tissulaire. Ce dialogue entre l'épithélium et le mésenchyme, n'existe pas de la même manière in-vitro. Il en résulte donc un défaut de réponse mésenchymale médiée par PPARβ, d'où le paradoxe entre les conditions in-vivo et in-vitro.Ces observations indiquent l'implication possible de PPARβ dans les lesions actiniques, en tant que conséquence naturelle de la radiothérapie de patients avec un cancer. Les mécanismes précis de l'action de PPARβ nécessitent une exploration approfondie de son rôle physiologique dans ce contexte.

Protective effect of intravitreal injection of vasoactive intestinal peptide-loaded liposomes on experimental autoimmune uveoretinitis.

PURPOSE: The aim of this study was to investigate the effect of a single intravitreal (i.v.t.) injection of vasoactive intestinal peptide (VIP) loaded in rhodamine-conjugated liposomes (VIP-Rh-Lip) on experimental autoimmune uveoretinitis (EAU). METHODS: An i.v.t. injection of VIP-Rh-Lip, saline, VIP, or empty-(E)-Rh-Lip was performed simultaneously, either 6 or 12 days after footpad immunization with retinal S-antigen in Lewis rats. Clinical and histologic scores were determined. Immunohistochemistry and cytokine quantification by multiplex enzyme-linked immunosorbent assay were performed in ocular tissues. Systemic immune response was determined at day 20 postimmunization by measuring proliferation and cytokine secretion of cells from inguinal lymph nodes (ILNs) draining the immunization site, specific delayed-type hypersensitivity (DTH), and the serum concentration of cytokines. Ocular and systemic biodistribution of VIP-Rh-Lip was studied in normal and EAU rats by immunofluorescence. RESULTS: The i.v.t. injection of VIP-Rh-Lip performed during the afferent, but not the efferent, phase of the disease reduced clinical EAU and protected against retinal damage. No effect was observed after saline, E-Rh-Lip, or VIP injection. VIP-Rh-Lip and VIP were detected in intraocular macrophages and in lymphoid organs. In VIP-Rh-Lip-treated eyes, macrophages expressed transforming growth factor-beta2, low levels of major histocompatibility complex class II, and nitric oxide synthase-2. T-cells showed activated caspase-3 with the preservation of photoreceptors. Intraocular levels of interleukin (IL)-2, interferon-gamma (IFN-gamma), IL-17, IL-4, GRO/KC, and CCL5 were reduced with increased IL-13. At the systemic level, treatment reduced retinal soluble autoantigen lymphocyte proliferation, decreased IL-2, and increased IL-10 in ILN cells, and diminished specific DTH and serum concentration of IL-12 and IFN-gamma. CONCLUSIONS: An i.v.t. injection of VIP-Rh-Lip, performed during the afferent stage of immune response, reduced EAU pathology through the immunomodulation of intraocular macrophages and deviant stimulation of T-cells in ILN. Thus, the encapsulation of VIP within liposomes appears as an effective strategy to deliver VIP into the eye and is an efficient means of the prevention of EAU severity.

Partial cricotracheal resection for congenital subglottic stenosis in children: the effect of concomitant anomalies.

OBJECTIVE: To review the surgical outcomes of partial cricotracheal resection in children with severe congenital subglottic stenosis and define the effect of concomitant anomalies or syndromes affecting outcome. METHODS: Forty-one children with subglottic stenosis of congenital and mixed (acquired on congenital) etiologies who underwent partial cricotracheal resection were identified from a prospectively collected database. Children with congenital subglottic stenosis and concomitant anomalies/syndromes were compared to children with congenital subglottic stenosis with no syndromes or concomitant anomalies. Operation-specific decannulation rates and complication rates were the primary outcome measures. We performed a two-sample test of proportion using the STATA-10 software for categorical variables to detect differences in proportions. Significance was set at p value<0.05. RESULTS: Twenty-seven (66%) of 41 children had concomitant anomalies/syndromes and 14 (34%) had congenital subglottic stenosis without concomitant anomalies/syndromes. Four patients needed revision surgery in the concomitant anomaly group and two patients needed revision surgery in the non concomitant anomaly group before achieving decannulation. The operation-specific decannulation rate in the concomitant anomaly group was 85% and 86% in the non anomaly group. When compared to children without concomitant anomaly, children with concomitant anomalies were more likely to have delayed decannulation following partial cricotracheal resection. However, this difference was not found to be statistically significant. The complication and operation-specific decannulation rates after partial cricotracheal resection were comparable to children without concomitant anomalies. Mortality rate was 11% (three of 27 patients) in the group with associated congenital anomalies or syndromes. Two patients succumbed to the primary pathology and one patient died due to tracheostomy-tube obstruction. There was no post-operative death in the non anomaly group. CONCLUSION: Partial cricotracheal resection can be done safely and effectively in children with concomitant anomalies/syndromes to achieve decannulation. The post-operative course may be prolonged but the decannulation and the complication rates are comparable to those children with congenital subglottic stenosis without concomitant anomalies.

Gastrointestinal disease following heart transplantation.

With advances in heart transplantation, a growing number of recipients are at risk of developing gastrointestinal disease. We reviewed our experience with gastrointestinal disease in 92 patients undergoing 93 heart transplants. All had follow-up, with the median time 4.8 years (range 0.5-9.6 years). During the period of the study we progressively adopted a policy of low immunosuppression aiming toward monotherapy with cyclosporine. Nineteen patients (20.6%) developed 28 diseases related to the gastrointestinal tract. Thirteen patients required 18 surgical interventions, five as emergencies: closure of a duodenal ulcer, five cholecystectomies (one with biliary tract drainage), a sigmoid resection for a diverticulitis with a colovesical fistula, a colostomy followed by a colostomy takedown for an iatrogenic colon perforation, appendectomy, two anorectal procedures, and six abdominal wall herniorrhaphies. At the onset of gastrointestinal disease, 8 patients were on standard triple-drug immunosuppression, all of them within 6 months of transplantation; 13 were on double-drug immunosuppression; and 7 were on cyclosporine alone. All the patients with perforations/fistulas were on steroids. Among the 11 infectious or potentially infectious diseases, 10 were on triple- or double-drug immunosuppression. One death, a patient who was on triple-drug immunosuppression, had a postmortem diagnosis of necrotic and hemorrhagic pancreatitis. Except for an incisional hernia following a laparoscopic cholecystectomy, there was no morbidity and, importantly, no septic complications. We concluded that a low immunosuppression policy is likely to be responsible for the low morbidity and mortality of posttransplant gastrointestinal disease, with a lower incidence of viscous perforation/fistula and infectious gastrointestinal disease.

Recognition of Gram-positive Intestinal Bacteria by Hybridoma- and Colostrum-derived Secretory Immunoglobulin A Is Mediated by Carbohydrates.

Humans live in symbiosis with 10(14) commensal bacteria among which >99% resides in their gastrointestinal tract. The molecular bases pertaining to the interaction between mucosal secretory IgA (SIgA) and bacteria residing in the intestine are not known. Previous studies have demonstrated that commensals are naturally coated by SIgA in the gut lumen. Thus, understanding how natural SIgA interacts with commensal bacteria can provide new clues on its multiple functions at mucosal surfaces. Using fluorescently labeled, nonspecific SIgA or secretory component (SC), we visualized by confocal microscopy the interaction with various commensal bacteria, including Lactobacillus, Bifidobacteria, Escherichia coli, and Bacteroides strains. These experiments revealed that the interaction between SIgA and commensal bacteria involves Fab- and Fc-independent structural motifs, featuring SC as a crucial partner. Removal of glycans present on free SC or bound in SIgA resulted in a drastic drop in the interaction with Gram-positive bacteria, indicating the essential role of carbohydrates in the process. In contrast, poor binding of Gram-positive bacteria by control IgG was observed. The interaction with Gram-negative bacteria was preserved whatever the molecular form of protein partner used, suggesting the involvement of different binding motifs. Purified SIgA and SC from either mouse hybridoma cells or human colostrum exhibited identical patterns of recognition for Gram-positive bacteria, emphasizing conserved plasticity between species. Thus, sugar-mediated binding of commensals by SIgA highlights the currently underappreciated role of glycans in mediating the interaction between a highly diverse microbiota and the mucosal immune system.

Secretory IgA: an actor of the interplay between the commensal flora and the intestinal immune system?

In the gastro-intestinal tract,Peyers patches have been describedas a major inductive site for mucosalsecretory IgA (SIgA) responses directedagainst pathogens. The classicalview is that SIgAserves as the firstline of defense against microorganismsby agglutining potential invadersand faciliting their clearance byperistaltic and mucociliary movements,a mechanism called immuneexclusion. Our laboratory has shownthat SIgA is not only able to be"retrotransported" into Peyers patchesvia the associated M cells, but also todeliver sizeable cargos in the form ofSIgA-based immune complexes, resultingin the onset of non-inflammatorytype of responses. Such a novelfunction raises the question of thepossible role of mucosal SIgA in theinterplay with commensal bacteriaand the contribution of the antibody inbacterial homeostasis. To address thisquestion, Lactobacillus rhamnosus(LPR) was administered into a mouseligated loop comprising a Peyerspatch, in association or not with SIgA.The fate of fluorescently labelled bacteriawas followed by laser scanningconfocal microscopy at different incubationtimes. After 2 hours of incubationin the loop, LPR bacteria arefound more abundantly in thesubepithelial dome (SED) regionwhen they are coated with SIgA thanLPR administered alone despite theyare absent from neighboring villi.Herein, it is shown that this mechanismof entry involves M cells inPeyers pathes. After their sampling byM cells, bacteria are engulfed by thedendritic cells of the subjacent SEDregion. Interestingly, LPR bacteriaare found coated by the endogenousnatural SIgA present in mice intestinalsecretions, confirming the requirementof SIgA for this type of entry.The subsequent effect on the maturationof dendritic cells after interactionwith LPR was investigated in vitroin presence or not of SIgA by measuringthe expression of CD40, CD80and CD86 surface markers with flowcytometry analyses. Results show thatDCs respond in the same way in presenceof SIgA than with LPR bacteriaalone, indicating that SIgA does notmodulate the interaction betweenDCs and bacteria in this context. Thiswork gives new evidences about theinvolvement of SIgA in the mechanismby which the intestinal immunesystem permanently checks the contentof the intestine.

Transhiatal laparoscopic resection of intrathoracic esophageal duplication in a 6-month-old boy.

We report the case of a 6-month-old boy known antenatally to have a mediastinal cyst. Postnatal workup showed a noncommunicating compressive cyst bound to the lower third of the native esophagus. He underwent its removal by transhiatal laparoscopy. This appears to be the first case of laparoscopic removal of a thoracic esophageal duplication cyst in a child.