"How I Do It"-Radical Right Colectomy with Side-to-Side Stapled Ileo-Colonic Anastomosis.

BACKGROUND AND OBJECTIVE: Standardization of surgical technique helps to reproduce excellent clinical outcomes, especially in teaching institutions. We aim to describe in detail our established approach for oncological right colectomy. TECHNIQUE: The right colon is mobilized in a five-step latero-inferior approach starting off with (1) the terminal ileum, visualizing the duodenum and the head of pancreas. (2) The ascending colon is dissected from the retroperitoneum, and takedown of the hepatic flexure is completed coming retrograde from the transverse colon (3). (4) Transection of the remaining retroperitoneal attachments completes exposure of the duodenum and mobilization of the right colon. (5) Ileocolic vessels are dissected out and divided close to their origin, and the mesocolon is divided. We then establish intestinal continuity by use of a side-to-side stapled technique. (1) The arms of a linear cutting stapler are inserted via transverse incisions at the anti-mesenteric sides of the terminal ileum and the transverse colon (tenia) and fired. (2) The enterotomy site is closed by removal of the specimen using a second transverse firing of the linear cutting stapler. An important final step is the (3) reinforcement of the anastomotic ends and the crossing of the staple lines; an omental patch and closure of the mesenteric window are optional. CONCLUSION: The suggested standardized five-step lateral-to-medial dissection of the right colon and the three-step side-to-side stapled technique for ileo-colonic anastomosis are easy to learn and to reproduce. Careful adherence to pivotal technical details will help to obtain an optimal oncological outcome and a consistently low leak rate around 2 %.

Allergen-induced IgE-dependent gut inflammation in a human PBMC-engrafted murine model of allergy.

BACKGROUND: Humanized murine models comprise a new tool to analyze novel therapeutic strategies for allergic diseases of the intestine.¦OBJECTIVE: In this study we developed a human PBMC-engrafted murine model of allergen-driven gut inflammation and analyzed the underlying immunologic mechanisms.¦METHODS: Nonobese diabetic (NOD)-scid-γc(-/-) mice were injected intraperitoneally with human PBMCs from allergic donors together with the respective allergen or not. Three weeks later, mice were challenged with the allergen orally or rectally, and gut inflammation was monitored with a high-resolution video miniendoscopic system, as well as histologically.¦RESULTS: Using the aeroallergens birch or grass pollen as model allergens and, for some donors, also hazelnut allergen, we show that allergen-specific human IgE in murine sera and allergen-specific proliferation and cytokine production of human CD4(+) T cells recovered from spleens after 3 weeks could only be measured in mice treated with PBMCs plus allergen. Importantly, these mice had the highest endoscopic scores evaluating translucent structure, granularity, fibrin, vascularity, and stool after oral or rectal allergen challenge and a strong histologic inflammation of the colon. Analyzing the underlying mechanisms, we demonstrate that allergen-associated colitis was dependent on IgE, human IgE receptor-expressing effector cells, and the mediators histamine and platelet-activating factor.¦CONCLUSION: These results demonstrate that allergic gut inflammation can be induced in human PBMC-engrafted mice, allowing the investigation of pathophysiologic mechanisms of allergic diseases of the intestine and evaluation of therapeutic interventions.

Rendu-Osler disease: treatment with oestrogen/progestagen versus octreotide.

In Rendu-Osler disease, haemorrhages due to gastrointestinal vascular malformations are common. Surgical and endoscopic treatments for haemorrhage due to gastrointestinal vascular malformations are compromised when lesions are diffuse, escape identification or are inaccessible to treatment. Hormonal treatment with oestrogen and progestagens is still controversial based on contradictory results from two randomised clinical trials. Although somatostatin and its long-acting analogue, octreotide, have been reported to be beneficial in preventing rebleeding, there is no consensus on this type of treatment. This case report shows how the combination of ethinyloestradiol and norethisterone markedly reduced the need for blood transfusions with few side effects in one patient; in comparison, octreotide seems less effective but this could be related to a worsening of the disease.

High magnification cystoscopy in the primary diagnosis of bladder tumors.

Purpose of reviewIn bladder cancer, discrimination between benign and malignant tissue may remain tricky with current endoscopic tools. On the basis of our recent experience with high-magnification cystoscopy, compared with other tools such as optical coherence tomography or confocal laser endomicroscopy, it is suggested here that this discrimination may well be feasible endoscopically. The clinical potential of these systems that are being developed as complementary tools to the current endoscopic equipment is reviewed.Recent findingsAt present, white-light cystoscopy, either assisted by fluorescence cystoscopy or narrow-band imaging, is proposed for the global cystoscopic examination of bladder cancer patients. Both techniques compete to help to reduce the recurrence rate by improving exophytic tumor detection, and the extent of carcinoma in situ and high-grade dysplasia. All of which are important prognosis factors for disease progression. In addition, recent findings on neoangiogenesis that accompanies early stage bladder cancer show that this may also be an important observable switch in bladder cancerogenesis, as it is found very early in tumor development. The high magnification cystoscopy as a complementary tool to fluorescence cystoscopy allows classification of the vessel patterns on fluorescence positive sites, and thus facilitates the discrimination between cancerous and noncancerous lesions. This information may be useful to reduce the false positive rate of fluorescence cystoscopy.SummaryEmerging technologies aiming at a real-time in-situ discrimination between benign and malignant tissue during endoscopic bladder exploration is a promising development for the monitoring of bladder cancer patients.

Bihippocampal damage with emotional dysfunction: impaired auditory recognition of fear.

A right-handed man developed a sudden transient, amnestic syndrome associated with bilateral hemorrhage of the hippocampi, probably due to Urbach-Wiethe disease. In the 3rd month, despite significant hippocampal structural damage on imaging, only a milder degree of retrograde and anterograde amnesia persisted on detailed neuropsychological examination. On systematic testing of recognition of facial and vocal expression of emotion, we found an impairment of the vocal perception of fear, but not that of other emotions, such as joy, sadness and anger. Such selective impairment of fear perception was not present in the recognition of facial expression of emotion. Thus emotional perception varies according to the different aspects of emotions and the different modality of presentation (faces versus voices). This is consistent with the idea that there may be multiple emotion systems. The study of emotional perception in this unique case of bilateral involvement of hippocampus suggests that this structure may play a critical role in the recognition of fear in vocal expression, possibly dissociated from that of other emotions and from that of fear in facial expression. In regard of recent data suggesting that the amygdala is playing a role in the recognition of fear in the auditory as well as in the visual modality this could suggest that the hippocampus may be part of the auditory pathway of fear recognition.

Is the diagnostic yield of upper GI endoscopy improved by the use of explicit panel-based appropriateness criteria?

BACKGROUND: Increasing the appropriateness of use of upper gastrointestinal (GI) endoscopy is important to improve quality of care while at the same time containing costs. This study explored whether detailed explicit appropriateness criteria significantly improve the diagnostic yield of upper GI endoscopy. METHODS: Consecutive patients referred for upper GI endoscopy at 6 centers (1 university hospital, 2 district hospitals, 3 gastroenterology practices) were prospectively included over a 6-month period. After controlling for disease presentation and patient characteristics, the relationship between the appropriateness of upper GI endoscopy, as assessed by explicit Swiss criteria developed by the RAND/UCLA panel method, and the presence of relevant endoscopic lesions was analyzed. RESULTS: A total of 2088 patients (60% outpatients, 57% men) were included. Analysis was restricted to the 1681 patients referred for diagnostic upper GI endoscopy. Forty-six percent of upper GI endoscopies were judged to be appropriate, 15% uncertain, and 39% inappropriate by the explicit criteria. No cancer was found in upper GI endoscopies judged to be inappropriate. Upper GI endoscopies judged appropriate or uncertain yielded significantly more relevant lesions (60%) than did those judged to be inappropriate (37%; odds ratio 2.6: 95% CI [2.2, 3.2]). In multivariate analyses, the diagnostic yield of upper GI endoscopy was significantly influenced by appropriateness, patient gender and age, treatment setting, and symptoms. CONCLUSIONS: Upper GI endoscopies performed for appropriate indications resulted in detecting significantly more clinically relevant lesions than did those performed for inappropriate indications. In addition, no upper GI endoscopy that resulted in a diagnosis of cancer was judged to be inappropriate. The use of such criteria improves patient selection for upper GI endoscopy and can thus contribute to efforts aimed at enhancing the quality and efficiency of care. (Gastrointest Endosc 2000;52:333-41).

Altered expression of CD44 and DKK1 in the progression of Barrett's esophagus to esophageal adenocarcinoma.

Barrett's esophagus (BE) is an acquired condition in which the normal lining of the esophagus is replaced by intestinal metaplastic epithelium. BE can evolve to esophageal adenocarcinoma (EAC) through low-grade dysplasia (LGD) and high-grade dysplasia (HGD). The only generally accepted marker for increased risk of EAC is the presence of HGD, diagnosed on endoscopic biopsies. More specific markers for the prediction of EAC risk are needed. A tissue microarray was constructed comprising tissue samples from BE, LGD, HGD, and EAC. Marker expression was studied by immunohistochemistry using antibodies against CD44, DKK1, CDX2, COX2, SOX9, OCT1, E-cadherin, and beta-catenin. Immunostaining was evaluated semi-quantitatively. CD44 expression decreased in HGD and EAC relative to BE and LGD. DKK1 expression increased in HGD and EAC relative to BE and LDG. CDX2 expression increased in HGD but decreased in EAC. COX2 expression decreased in EAC, and SOX9 expression increased only in the upper crypt epithelial cells in HGD. E-cadherin expression decreased in EAC. Nuclear beta-catenin was not significantly different between BE, LGD, and HGD. Loss of CD44 and gain of DKK1 expression characterizes progression from BE and LGD to HGD and EAC, and their altered expression might indicate an increased risk for developing an EAC. This observation warrants inclusion of these immunohistochemically detectable markers in a study with a long patient follow-up.

Gaslini's tracheal team: preliminary experience after one year of paediatric airway reconstructive surgery.

Background: congenital and acquired airway anomalies represent a relatively common albeit challenging problem in a national tertiary care hospital. In the past, most of these patients were sent to foreign Centres because of the lack of local experience in reconstructive surgery of the paediatric airway. In 2009, a dedicated team was established at our Institute. Gaslini's Tracheal Team includes different professionals, namely anaesthetists, intensive care specialists, neonatologists, pulmonologists, radiologists, and ENT, paediatric, and cardiovascular surgeons. The aim of this project was to provide these multidisciplinary patients, at any time, with intensive care, radiological investigations, diagnostic and operative endoscopy, reconstructive surgery, ECMO or cardiopulmonary bypass. Aim of this study is to present the results of the first year of airway reconstructive surgery activity of the Tracheal Team.Methods: between September 2009 and December 2010, 97 patients were evaluated or treated by our Gaslini Tracheal Team. Most of them were evaluated by both rigid and flexible endoscopy. In this study we included 8 patients who underwent reconstructive surgery of the airways. Four of them were referred to our centre or previously treated surgically or endoscopically without success in other Centres.Results: Eight patients required 9 surgical procedures on the airway: 4 cricotracheal resections, 2 laryngotracheoplasties, 1 tracheal resection, 1 repair of laryngeal cleft and 1 foreign body removal with cardiopulmonary bypass through anterior tracheal opening. Moreover, in 1 case secondary aortopexy was performed. All patients achieved finally good results, but two of them required two surgeries and most required endoscopic manoeuvres after surgery. The most complex cases were the ones who had already been previously treated.Conclusions: The treatment of paediatric airway anomalies requires a dedicated multidisciplinary approach and a single tertiary care Centre providing rapid access to endoscopic and surgical manoeuvres on upper and lower airways and the possibility to start immediately cardiopulmonary bypass or ECMO.The preliminary experience of the Tracheal Team shows that good results can be obtained with this multidisciplinary approach in the treatment of complicated cases. The centralization of all the cases in one or few national Centres should be considered.

Evaluación de un nuevo método de sutura para la cirugía endoscopica transluminal a través de orificios naturales en un modelo animal

Natural Orifice Transluminal Endoscopic Surgery (NOTES) is a novel, potentially less invasive alternative to laparoscopic surgery. However, the problems of transluminal access and closure represent significant obstacles to its successful introduction in humans. Objective: to evaluate the feasibility and safety of a novel device designed for transluminal access and closure in a survival porcine model. Subjects: Four adult female Yorkshire pigs were used in the study. Interventions: While under general anesthesia, the animals were prepared with multiple tap water enemas followed by instillation of an antibiotic suspension and povidone-iodine lavage. At a distance of 15 to 20 cm from the anus, the prototype device (LSI Solutions, Victor, NY, USA) deployed a circumscribing purse-string suture around the planned incision site and subsequently used a blade mechanism to create a 2.5-cm linear incision. The transcolonic incision was then closed by cinching and securing the purse-string suture with a titanium knot by use of a separate hand-activated suture-locking device. Main Outcome Measurements: The animals were monitored daily for signs of peritonitis and sepsis and were survived for 14 days. The peritoneal cavity was examined for peritonitis, and the colonic incision site was examined for wound dehiscence, pericolic abscess formation, and gross adhesions. Tissue samples from both incisional and random peritoneal sites were obtained for histologic examination. Results: Transcolonic incision and closure were successful in all 4 animals. The device performed in a rapid and reproducible fashion. All animals recovered without septic complications. At necropsy, there was no evidence of peritonitis, abscesses, or wound dehiscence. Salpingocolonic and colovesicular adhesions were noted in 3 of 4 animals. Histologic examination revealed microabscesses at the incision site in all animals. Conclusions: The prototype incision and closure device represents a promising solution to the problems of transluminal access for NOTES. The presence of incision-related adhesions and microabscesses signal the need for further refinement in aseptic technique. 

Myosin Vs organize actin cables in fission yeast.

Myosin V motors are believed to contribute to cell polarization by carrying cargoes along actin tracks. In Schizosaccharomyces pombe, Myosin Vs transport secretory vesicles along actin cables, which are dynamic actin bundles assembled by the formin For3 at cell poles. How these flexible structures are able to extend longitudinally in the cell through the dense cytoplasm is unknown. Here we show that in myosin V (myo52 myo51) null cells, actin cables are curled, bundled, and fail to extend into the cell interior. They also exhibit reduced retrograde flow, suggesting that formin-mediated actin assembly is impaired. Myo52 may contribute to actin cable organization by delivering actin regulators to cell poles, as myoV defects are partially suppressed by diverting cargoes toward cell tips onto microtubules with a kinesin 7-Myo52 tail chimera. In addition, Myo52 motor activity may pull on cables to provide the tension necessary for their extension and efficient assembly, as artificially tethering actin cables to the nuclear envelope via a Myo52 motor domain restores actin cable extension and retrograde flow in myoV mutants. Together these in vivo data reveal elements of a self-organizing system in which the motors shape their own tracks by transporting cargoes and exerting physical pulling forces.

Small Bowel Bacterial Overgrowth is found in 71% of IBS patients and associated symptoms respond wel to Rifaximin in a phase IV trial

Background: The prevalence of small intestinal bowel bacterial overgrowth (SIBO) in patients with irritable bowel syndrome (IBS) ranges from 43% to 78% as determined by the lactulose hydrogen breath (LHBT) test. Although rifaximine, a non-absorbable antibiotic, has been able to decrease global IBS symptoms as well as bloating in placebo-controlled randomized trials, these results were not repeated in phase IV studies in daily clinical practice. Aim: To assess the prevalence of SIBO in an IBS cohort and to evaluate the treatment response in the IBS cohort affected by SIBO. Methods: Enrolled patients were diagnosed with IBS using the following criteria: fulfillment of the Rome III criteria, absence of alarm symptoms (anemia, weight loss, nocturnal symptoms etc), normal fecal calproectin, normal endoscopic workup including histology. Celiac disease was excluded by serology and/or duodenal biopsy. All patients underwent lactulose hydrogen breath testing (LHBT) for SIBO diagnosis. Patients with SIBO were treated with rifaximine tablets (400mg twice daily for 14 days). Both before and at week 6 after rifaximin treatment, patients completed a questionnaire, where the following criteria were assessed individually using 11-point Likert scales: the bloating, flatulence, abdominal pain, diarrhea, and overall well-being. Results: Hundred-fifty IBS patients were enrolled (76% female, mean age 44 ± 16 years), of whom 106 (71%) were diagnosed with SIBO and consequently treated with rifaximine. Rifaximine treatment significantly reduced the following symptoms as assessed by the symptom questionnaire: bloating (5.5 ± 2.6 before vs. 3.6 ± 2.7 after treatment, p <0.001), flatulence (5 ± 2.7 vs. 4 ± 2.7, p = 0.015), diarrhea (2.9 ± 2.4 vs. 2 ± 2.4, p = 0.005), abdominal pain (4.8 ± 2.7 vs. 3.3 ± 2.5, p <0.001) and resulted in improved overall well-being (3.9 ± 2.4 vs. 2.7 ± 2.3, p <0.001). Thirteen of the 106 treated patients were lost to follow-up (12%). The LHBT was repeated 2-4 weeks after rifaximine treatment in 65/93 (70%) patients. Eradication of SIBO was documented in 85% of all patients (55/65), whereas 15% of patients (10/65) tested positive for SIBO as determined by the LHBT testing. Conclusions: The results of our phase IV trial indicate that a high proportion of IBS patients tested positive for SIBO. IBS symptoms (bloating, flatulence, diarrhea, pain, overall well-being) were significantly diminished following a 2-week treatment with rifaximine. These results support the previous findings of randomized controlled trials that the presence of SIBO is associated with symptom generation in IBS patients and that reduction and/or elimination of SIBO may help to alleviate IBSassociated symptoms.

Severity of endoscopically detected esophageal inflammatory and fibrostenotic features correlates with degree of esophageal eosinophilia in adults with eosinophilic esophagitis

Background: Eosinophilic esophagitis (EoE) has emerged as a leading cause of dysphagia in adults. Characteristic esophageal features on endoscopy include structural/fibrostenotic (rings, narrow caliber, strictures) and inflammatory manifestations (longitudinal furrows, exudates, edema). Aim: The purpose of this study was to correlate the clinical, endoscopic and histopathologic features in adult EoE patients. Methods: A total of 106 encounters of 81 patients with EoE were analyzed. Data included an EoE-directed symptom-severity patient questionnaire evaluating symptoms of dysphagia (frequency, intensity, duration), meal duration, chest pain, and overall symptom severity. Video recordings of endoscopies were reviewed in a blinded manner using a classification and grading scheme for the esophageal features of EoE. Histopathology was reviewed for peak eosinophil count/high power field by pathologists blinded to the patients' clinical status. Associations between endoscopic features, histology and symptoms were evaluated using the Spearman rank correlation analysis. Results: The endoscopic severity of both structural and inflammatory esophageal features of EoE, including rings, exudates, longitudinal furrows, and edema, correlated significantly with peak eosinophil counts (see Table 1). Presence of "crepe paper mucosa" did not demonstrate significant association with peak eosinophil counts. Both structural (rings, narrow-caliber esophagus and strictures) and inflammatory (furrows, exudates and edema) composite endoscopic scores demonstrated a strong correlation with peak eosinophil counts. The strongest association with the degree of esophageal eosinophilia was found with a combination of both structural and inflammatory findings (p < 0.0001). The esophageal diameter (in mm) was negatively correlated with overall symptom severity (Spearman's rho = -0.4883, P = 0.0339). None of the individual or combined patient reported symptoms correlated significantly with either endoscopic or histopathologic findings. Conclusion: The severity of both structural and inflammatory endoscopic features associated with EoE is significantly associated with the degree of esophageal eosinophilia. Patient reported symptom severity was not associated with the degree of esophageal eosinophilia. Esophageal stricture diameter was inversely correlated with EoE symptom severity. The prognostic and therapeutic implications of these observations need to be determined.

Cytostatic lung perfusion results in heterogeneous spatial regional blood flow and drug distribution: evaluation of different cytostatic lung perfusion techniques in a porcine model.

OBJECTIVES: Comparison of doxorubicin uptake, leakage and spatial regional blood flow, and drug distribution was made for antegrade, retrograde, combined antegrade and retrograde isolated lung perfusion, and pulmonary artery infusion by endovascular inflow occlusion (blood flow occlusion), as opposed to intravenous administration in a porcine model. METHODS: White pigs underwent single-pass lung perfusion with doxorubicin (320 mug/mL), labeled 99mTc-microspheres, and Indian ink. Visual assessment of the ink distribution and perfusion scintigraphy of the perfused lung was performed. 99mTc activity and doxorubicin levels were measured by gamma counting and high-performance liquid chromatography on 15 tissue samples from each perfused lung at predetermined localizations. RESULTS: Overall doxorubicin uptake in the perfused lung was significantly higher (P = .001) and the plasma concentration was significantly lower (P < .0001) after all isolated lung perfusion techniques, compared with intravenous administration, without differences between them. Pulmonary artery infusion (blood flow occlusion) showed an equally high doxorubicin uptake in the perfused lung but a higher systemic leakage than surgical isolated lung perfusion (P < .0001). The geometric coefficients of variation of the doxorubicin lung tissue levels were 175%, 279%, 226%, and 151% for antegrade, retrograde, combined antegrade and retrograde isolated lung perfusion, and pulmonary artery infusion by endovascular inflow occlusion (blood flow occlusion), respectively, compared with 51% for intravenous administration (P = .09). 99mTc activity measurements of the samples paralleled the doxorubicin level measurements, indicating a trend to a more heterogeneous spatial regional blood flow and drug distribution after isolated lung perfusion and blood flow occlusion compared with intravenous administration. CONCLUSIONS: Cytostatic lung perfusion results in a high overall doxorubicin uptake, which is, however, heterogeneously distributed within the perfused lung.

Hémorragie digestive aiguë [Acute gastrointestinal bleeding]

Gastrointestinal bleeding is among the major clinical challenges for the gastroenterologists and the initial approach is very complex. For a big part of bleeding lesions, it is important to perform an endoscopic hemostatis after the introduction of an intravenous treatment (that has to be started as soon as there is a clinical suspicion of an upper gastrointestinal bleeding). The significant progresses made during the last years have allowed firstly to see the entire small bowel mucosa (video capsule) and secondly new treatments have successfully replaced surgical interventions.

Swallowed topical corticosteroids reduce the risk for long-lasting bolus impactions in eosinophilic esophagitis.

BACKGROUND: Long-lasting food impactions requiring endoscopic bolus removal occur frequently in patients with eosinophilic esophagitis (EoE) and harbor a risk for severe esophageal injuries. We evaluated whether treatment with swallowed topical corticosteroids is able to reduce the risk of occurrence of this complication. METHODS: We analyzed data from the Swiss EoE Cohort Study. Patients with yearly clinic visits, during which standardized assessment of symptoms, endoscopic, histologic, and laboratory findings was carried out, were included. RESULTS: A total of 206 patients (157 males) were analyzed. The median follow-up time was 5 years with a total of 703 visits (mean 3.41 visits/patient). During the follow-up period, 33 patients (16 % of the cohort) experienced 42 impactions requiring endoscopic bolus removal. We evaluated the following factors regarding the outcome 'bolus impaction' by univariate logistic regression modeling: swallowed topical corticosteroid therapy (OR 0.503, 95%-CI 0.255-0.993, P = 0.048), presence of EoE symptoms (OR 1.150, 95%-CI 0.4668-2.835, P = 0.761), esophageal stricture (OR 2.832, 95%-CI 1.508-5.321, P = 0.001), peak eosinophil count >10 eosinophils/HPF (OR 0.724, 95%-CI 0.324-1.621, P = 0.433), blood eosinophilia (OR 1.532, 95%-CI 0.569-4.118, P = 0.398), and esophageal dilation (OR 1.852, 95%-CI 1.034-3.755, P = 0.017). In the multivariate model, the following factors were significantly associated with bolus impaction: swallowed topical corticosteroid therapy (OR 0.411, 95%-CI 0.203-0.835, P = 0.014) and esophageal stricture (OR 2.666, 95%-CI 1.259-5.645, P = 0.01). Increasing frequency of use of swallowed topical steroids was associated with a lower risk for bolus impactions. CONCLUSIONS: Treatment of EoE with swallowed topical corticosteroids significantly reduces the risk for long-lasting bolus impactions.