Pacemaker therapy in patients with neurally mediated syncope and documented asystole: Third International Study on Syncope of Uncertain Etiology (ISSUE-3): a randomized trial.

BACKGROUND: The efficacy of cardiac pacing for prevention of syncopal recurrences in patients with neurally mediated syncope is controversial. We wanted to determine whether pacing therapy reduces syncopal recurrences in patients with severe asystolic neurally mediated syncope. METHODS AND RESULTS: Double-blind, randomized placebo-controlled study conducted in 29 centers in the Third International Study on Syncope of Uncertain Etiology (ISSUE-3) trial. Patients were ≥40 years, had experienced ≥3 syncopal episodes in the previous 2 years. Initially, 511 patients, received an implantable loop recorder; 89 of these had documentation of syncope with ≥3 s asystole or ≥6 s asystole without syncope within 12 ± 10 months and met criteria for pacemaker implantation; 77 of 89 patients were randomly assigned to dual-chamber pacing with rate drop response or to sensing only. The data were analyzed on intention-to-treat principle. There was syncope recurrence during follow-up in 27 patients, 19 of whom had been assigned to pacemaker OFF and 8 to pacemaker ON. The 2-year estimated syncope recurrence rate was 57% (95% CI, 40-74) with pacemaker OFF and 25% (95% CI, 13-45) with pacemaker ON (log rank: P=0.039 at the threshold of statistical significance of 0.04). The risk of recurrence was reduced by 57% (95% CI, 4-81). Five patients had procedural complications: lead dislodgment in 4 requiring correction and subclavian vein thrombosis in 1 patient. CONCLUSIONS: Dual-chamber permanent pacing is effective in reducing recurrence of syncope in patients ≥40 years with severe asystolic neurally mediated syncope. The observed 32% absolute and 57% relative reduction in syncope recurrence support this invasive treatment for the relatively benign neurally mediated syncope. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00359203.

Assessing the epidemiology and pattern of care of colorectal cancer in Valais, Switzerland

Background: The Valais's cancer registry (RVsT) of the Observatoire valaisan de le santé (OVS) and the department of oncology of Valais's Hospital conducted a study on the epidemiology and pattern of care of colorectal cancer in Valais. Colorectal cancer is the third cause of death by cancer in Switzerland with about 1600 deaths per year. It is the third most frequent cancer for males and the second most frequent for females in Valais. The number of new colorectal cancer cases (average per year) increased between 1989 and 2009 for males as well as for females in Valais. The number of colorectal cancer death cases (average per year) slightly increased between 1989 and 2009 for males as well as for females in Valais. Age-standardized rates of incidence were stable for males and females in Valais and in Switzerland between 1989 and 2009, while age-standardized rates of mortality decreased for males and females in Valais and Switzerland. Results: 774 cases were recorded (59% males). Median age at diagnosis was 70 years old. Most of cancers were invasive (79%) and the main localization was the colon (71%). The most frequent mode of detection was a consultation for non emergency symptoms (75%), but almost 10% of patients consulted in emergency. 82% of patients were treated within 30 days from diagnosis. 90% of the patients were treated by surgery alone or with combined treatment. The first treatment was surgery, including endoscopic resection in 86% of the cases. The treatment was different according to the localization and the stage of the cancer. Survival rate was 95% at 30 days and 79% at one year. The survival was dependent on the stage and the age at diagnosis. Cox model shows an association between mortality and age (better survival for young people) and between mortality and stage (better survival for the lower stages). Methods: RVsT collects information on all cancer cases since 1989 for people registered in the communes of Valais. RVsT has an authorization to collect non anonymized data. All new incident cancers are coded according to the International Classification of Diseases for Oncology (ICD-O-3) and the stages are coded according to the TNM classification. We studied all cases of in situ and invasive colorectal cancers diagnosed between 2006 and 2009 and registered routinely at the RVsT. We checked for data completeness and if necessary sent questionnaires to avoid missing data. A distance of 15 cm has been chosen to delimitate the colon (sigmoid) and the rectal cancers. We made an active follow-up for vital status to have a valid survival analysis. We analyzed the characteristics of the tumors according to age, sex, localization and stage with stata 9 software. Kaplan-Meier curves were generated and Cox model were fitted to analyze survival. Conclusion: The characteristics of patients and tumors and the one year survival were similar to those observed in Switzerland and some European countries. Patterns of care were close to those recommended in guidelines. Routine data recorded in a cancer registry can be used, not only to provide general statistics, but also to help clinicians assess local practices.

Sorafenib as third- or fourth-line treatment of advanced gastrointestinal stromal tumour and pretreatment including both imatinib and sunitinib, and nilotinib: A retrospective analysis.

BACKGROUND: Tyrosine kinase inhibitors (TKI) improve the outcome of patients with advanced gastrointestinal stromal tumour (GIST), but treatment failure is frequent, and prognosis then bleak. Smaller trials in this setting suggested activity for sorafenib, a multikinase inhibitor of receptor tyrosine kinases and RAF serine/threonine kinases. PATIENTS AND METHODS: We retrospectively evaluated the efficacy of sorafenib, starting dose 400mg twice daily, in a large community-based cohort of 124 patients treated in 12 European and one United States (U.S.) cancer centre. All but one patient had a WHO performance score 0-2. All had failed both imatinib and sunitinib, 68 patients nilotinib and 26 had failed investigational therapy, too. RESULTS: Twelve (10%) patients responded to sorafenib and 70 (57%) patients achieved disease stabilisation. Sorafenib was moderately tolerated, and toxicity reported in 56% of the patients. Rash, hand-foot-syndrome and diarrhea occurred frequently. Sorafenib dosage was reduced in a third of patients, but this did not have an impact on progression-free survival (PFS) (p=0.15). Median PFS was 6.4months (95% confidence interval [CI], 4.6-8.0months) and median overall survival (OS) 13.5months (95% CI, 10.0-21.0months). Patients with a good performance status and those who responded to sorafenib had a significant better PFS. CONCLUSION: We conclude that sorafenib is active in GIST resistant to imatinib, sunitinib and nilotinib. These results warrant further investigation of sorafenib or similar molecules in GIST.

Hemobilia, a rare cause of acute pancreatitis after percutaneous liver biopsy: diagnosis and treatment by endoscopic retrograde cholangiopancreatography.

We here report the case history of a 75-yr-old woman who developed pancreatitis and recurrent symptomatic, cholestasis-induced hemobilia after percutaneous liver biopsy. An endoscopic sphincterotomy with clot extraction led to relief of symptoms. The risk of hemobilia after percutaneous liver biopsy is less than one per 1000 procedures, and only two cases of acute pancreatitis after percutaneous liver biopsy have previously been reported. To our knowledge, this is the first case in which endoscopic retrograde cholangiopancreatography was used to both diagnostic and therapeutic ends.

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.

How do Swiss Gastroenterologists assess Activity of Inflammatory Bowel Disease in Daily Practice: by Clinical Indices, Endoscopic Activity, or Biomarkers?

Background a nd A ims: There is a n ongoing d ebate which i sthe most appropriate w ay t o measure inflammatory boweldisease (IBD) activity (be it b y clinical i ndices, e ndoscopy, orbiomarkers). Accumulating evidence associates m ucosalhealing with a reduction in I BD-related s urgery andhospitalizations. We a imed to i nvestigate which outcomeparameters are used in daily practice for IBD monitoring.Methods: A q uestionnaire was sent in J uly 2010 t o all boardcertified gastroenterologists in S witzerland to evaluate t heassessment strategy of IBD activity, t he items on whichtherapeutic decisions w ere based upon, and the kind ofbiomarkers used for monitoring IBD activity.Results: Response rate was 57% (153/270). Mean physician'sage was 5 0±9years, mean duration o f gastroenterologicpractice 1 4±8years, 52% of them were working in p rivatepractice a nd 48% in h ospitals. S eventy-eight percent usedclinical activity i ndices as g old standard for IBD activityassessment, followed by 15% choosing endoscopic activity, and7% favouring biomarkers. Gastroenterologists based theirtherapeutic decisions in 70% on clinical activity indices, 24% onendoscopic activity, a nd 6% o n biomarkers. Most frequentlyused biomarkers were C-reactive protein (94%), complete bloodcount (78%) and fecal calprotectin (74%).Conclusions: I n daily p ractice, most IBD patients a remonitored based u pon t heir clinical a ctivity. B iomarkers a reperceived as l ess important compared to clinical andendoscopic activity. S imilar to activity a ssessment, alsotherapeutic decisions a re mostly made on the basis of clinicalactivity indices. The upcoming scientific evidence on the impactof mucosal h ealing does n ot yet seem to influence the dailypractice of gastroenterologists.

Anatomical landmarks for transnasal endoscopic skull base surgery

La résection par voie endoscopique transnasale de tumeurs envahissant la base du crâne antérieure a été récemment décrite. Cette chirurgie requiert une connaissance précise des repères anatomiques endoscopiques afin réduire le risque de complications vasculaires et neurologiques.¦Nous avons réalisé une étude anatomique endoscopique sur 6 têtes dont 3 injectées avec du silicone coloré. Les repères anatomiques pour les abords de 3 régions d'importance clinique ont été étudiés. Les repères pour l'abord de l'apex orbitaire sont le recessus carotidien latéral, l'empreinte du nerf optique, « l'optic strut » et le V2. Leurs rapports avec le canal optique, l'artère carotide interne et les fentes orbitaires supérieures et inférieures sont décrits. Les repères pour l'abord de l'apex pétreux sont le V2 et le nerf vidien qui permettent repérer la portion intrapétreuse de l'artère carotide interne. Les repères pour l'abord de la fosse ptérygomaxillaire sont le V2 et le foramen rotundum, l'artère et le trou sphénopalatins et l'artère maxillaire interne.¦Cette nouvelle approche permettant d'aborder des lésions médianes et paramédianes ouvre de nouvelles perspectives pour des équipes de neurochirurgiens et d'ORL. Ces voies d'abords s'appliquent aussi bien à des résections décompressives à but palliatif qu'à l'exérèse de tumeurs benignes et malignes, bien que les résultats à long terme doivent encore être validés pour cette dernière indication.

Efficient transduction of dendritic cells and induction of a T-cell response by third-generation lentivectors.

In order to induce a therapeutic T lymphocyte response, recombinant viral vaccines are designed to target professional antigen-presenting cells (APC) such as dendritic cells (DC). A key requirement for their use in humans is safe and efficient gene delivery. The present study assesses third-generation lentivectors with respect to their ability to transduce human and mouse DC and to induce antigen-specific CD8+ T-cell responses. We demonstrate that third-generation lentivectors transduce DC with a superior efficiency compared to adenovectors. The transfer of DC transduced with a recombinant lentivector encoding an antigenic epitope resulted in a strong specific CD8+ T-cell response in mice. The occurrence of lower proportions of nonspecifically activated CD8+ cells suggests a lower antivector immunity of lentivector compared to adenovector. Thus, lentivectors, in addition to their promise for gene therapy of brain disorders might also be suitable for immunotherapy.

Fecal calprotectin more accurately reflects endoscopic activity of ulcerative colitis than the Lichtiger Index, CRP, and blood leukocytes

Background: Thus far, the correlation of noninvasive markers with endoscopic activity in ulcerative colitis (UC) according to the modified Baron Index is unknown. We aimed to evaluate the correlation between endoscopic activity and fecal calprotectin (FC), C-reactive protein (CRP), blood leukocytes, and the Lichtiger Index (clinical score). Methods: UC patients undergoing complete colonoscopy were prospectively enrolled and scored clinically and endoscopically in an independent fashion. Fecal and blood samples were analyzed in UC patients and controls. Results: We enrolled 228 UC patients and 52 controls. Endoscopic disease activity correlated best with FC (Spearman's rank correlation coefficient r = 0.821), followed by the Lichtiger Index (r = 0.682), CRP (r = 0.556), and leukocytes (r = 0.401). FC was the only marker discriminating between different grades of endoscopic activity (grade 0, 20}11 mg/g; grade 1, 44}34 mg/g; grade 2, 111}74 mg/g; grade 3, 330}332 mg/g; grade 4, 659}319 mg/g; P = 0.0018 for discriminating grade 0 vs. 1 and P < 0.001 for discriminating all other grades). FC had the highest overall accuracy (91%) to detect endoscopically active disease (modified Baron Index _2), followed by the Lichtiger Index of _4 (77%), CRP larger than 5 mg/L (69%) and blood leukocytosis (58%). Conclusions: FC better correlated with the endoscopic disease activity than clinical activity, CRP, and blood leukocytes. The strong correlation with endoscopic disease activity suggests that FC represents a useful biomarker for noninvasive monitoring of disease activity in UC patients.

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

Complications of different ventilation strategies in endoscopic laryngeal surgery: a 10-year review.

BACKGROUND: Spontaneous ventilation, mechanical controlled ventilation, apneic intermittent ventilation, and jet ventilation are commonly used during interventional suspension microlaryngoscopy. The aim of this study was to investigate specific complications of each technique, with special emphasis on transtracheal and transglottal jet ventilation. METHODS: The authors performed a retrospective single-institution analysis of a case series of 1,093 microlaryngoscopies performed in 661 patients between January 1994 and January 2004. Data were collected from two separate prospective databases. Feasibility and complications encountered with each technique of ventilation were analyzed as main outcome measures. RESULTS: During 1,093 suspension microlaryngoscopies, ventilation was supplied by mechanical controlled ventilation via small endotracheal tubes (n = 200), intermittent apneic ventilation (n = 159), transtracheal jet ventilation (n = 265), or transglottal jet ventilation (n = 469). Twenty-nine minor and 4 major complications occurred. Seventy-five percent of the patients with major events had an American Society of Anesthesiologists physical status classification of III. Five laryngospasms were observed with apneic intermittent ventilation. All other 24 complications (including 7 barotrauma) occurred during jet ventilation. Transtracheal jet ventilation was associated with a significantly higher complication rate than transglottal jet ventilation (P < 0.0001; odds ratio, 4.3 [95% confidence interval, 1.9-10.0]). All severe complications were related to barotraumas resulting from airway outflow obstruction during jet ventilation, most often laryngospasms. CONCLUSIONS: The use of a transtracheal cannula was the major independent risk factor for complications during jet ventilation for interventional microlaryngoscopy. The anesthetist's vigilance in clinically detecting and preventing outflow airway obstruction remains the best prevention of barotrauma during subglottic jet ventilation.

Endoluminal surgical triangulation: overcoming challenges of colonic endoscopic submucosal dissections using a novel flexible endoscopic surgical platform: feasibility study in a porcine model.

BACKGROUND: Colonic endoscopic submucosal dissection (ESD) is challenging as a result of the limited ability of conventional endoscopic instruments to achieve traction and exposure. The aim of this study was to evaluate the feasibility of colonic ESD in a porcine model using a novel endoscopic surgical platform, the Anubiscope (Karl Storz, Tüttlingen, Germany), equipped with two working channels for surgical instruments with four degrees of freedom offering surgical triangulation. METHODS: Nine ESDs were performed by a surgeon without any ESD experience in three swine, at 25, 15, and 10 cm above the anal verge with the Anubiscope. Sixteen ESDs were performed by an experienced endoscopist in five swine using conventional endoscopic instruments. Major ESD steps included the following for both groups: scoring the area, submucosal injection of glycerol, precut, and submucosal dissection. Outcomes measured were as follows: dissection time and speed, specimen size, en bloc dissection, and complications. RESULTS: No perforations occurred in the Anubis group, while there were eight perforations (50 %) in the conventional group (p = 0.02). Complete and en bloc dissections were achieved in all cases in the Anubis group. Mean dissection time for completed cases was statistically significantly shorter in the Anubis group (32.3 ± 16.1 vs. 55.87 ± 7.66 min; p = 0.0019). Mean specimen size was higher in the conventional group (1321 ± 230 vs. 927.77 ± 229.96 mm(2); p = 0.003), but mean dissection speed was similar (35.95 ± 18.93 vs. 23.98 ± 5.02 mm(2)/min in the Anubis and conventional groups, respectively; p = 0.1). CONCLUSIONS: Colonic ESDs were feasible in pig models with the Anubiscope. This surgical endoscopic platform is promising for endoluminal surgical procedures such as ESD, as it is user-friendly, effective, and safe.