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Endoscopic submucosal dissection in patients with early esophageal squamous cell carcinoma: results from a prospective Western series

BACKGROUND Although endoscopic submucosal dissection (ESD) is becoming accepted as an established treatment for superficial esophageal squamous cell neoplasia, the majority of data on this endoscopic modality has been provided by Japanese series. OBJECTIVE To assess the efficacy and safety of ESD for esophageal squamous cell neoplasia in a consecutive series of patients treated in a Western setting. DESIGN AND SETTING Single-center, prospective observational study. PATIENTS AND INTERVENTION From January 2005 to July 2008, 20 patients with superficial esophageal squamous cell neoplasia were treated by ESD. MAIN OUTCOME MEASUREMENTS Rates of en bloc resection, complete resection, and complications were evaluated as short-term outcomes. Overall survival, local or distant recurrence, and postoperative stricture rates were evaluated as long-term outcomes. RESULTS ESD was performed in 20 patients (mean age 64 years, range 46-81 years; 16 men). The mean size of the lesion was 32 mm (range 15-60 mm); it was 30 mm or larger in 14 patients (70%). The mean time of ESD was 89 minutes (range 58-180 minutes). En bloc resection with resection-free margins was achieved in 18 patients (90%), whereas 2 patients presented with incomplete or indeterminate resection. Two cases (10%) of mediastinal emphysema without overt perforation and 1 case (5%) of post-ESD symptomatic stricture were reported. No local or distant post-ESD recurrence occurred in those with resection-free margins at a median follow-up of 18 months. LIMITATIONS Small number of patients and limited follow-up. CONCLUSION This Western series study confirms that ESD is a potentially curative treatment for superficial esophageal squamous cell neoplasia. Early and late complication rates were comparable to those of Japanese series. ESD should be probably considered as the treatment of choice in all large lesions amenable to endoscopic treatment.

A predictive model identifies patients most likely to have inadequate bowel preparation for colonoscopy.

BACKGROUND & AIMS An inadequate level of bowel preparation can affect the efficacy and safety of colonoscopy. Although some factors have been associated with outcome, there is no strategy to identify patients at high risk for inadequate preparation. We searched for factors associated with an inadequate level of preparation and tested the validity of a predictive clinical rule based on these factors. METHODS We performed a prospective study of 2811 consecutive patients who underwent colonoscopy examinations at 18 medical centers; clinical and demographic data were collected before the colonoscopy. Bowel preparation was classified as adequate or inadequate; 925 patients (33%) were found to have inadequate preparation. Multivariate analysis was used to identify factors associated with inadequate preparation, which were expressed as odds ratio (OR) and used to build a predictive model. RESULTS Factors associated with inadequate bowel preparation included being overweight (OR, 1.5), male sex (OR, 1.2), a high body mass index (OR, 1.1), older age (OR, 1.01), previous colorectal surgery (OR, 1.6), cirrhosis (OR, 5), Parkinson disease (OR, 3.2), diabetes (OR, 1.8), and positive results in a fecal occult test (OR, 0.6). These factors predicted which patients would have inadequate cleansing with 60% sensitivity, 59% specificity, 41% positive predictive value, and 76% negative predictive value; they had an under the receiver operating characteristic curve value of 0.63. Assuming 100% efficacy of a hypothetical regimen to address patients predicted to be at risk of inadequate preparation, the rate would decrease from 33% to 13%. CONCLUSIONS We identified factors associated with inadequate bowel preparation for colonoscopy and used these to build an accurate predictive model.

Clinical experience with a new endoscopic over-the-scope clip system for use in the GI tract

BACKGROUND The newly designed over-the-scope clip (OTSC) seems to overcome several limitations of current clipping system, such as size and opening-closing force, allowing better control of gastric or colonic bleeding and/or deep wall defect or perforation. AIMS The aim of this retrospective analysis was to describe the new endoscopic device and evaluate our first clinical experience. PATIENTS AND METHODS We treated with the OTSC system 9 patients (range, 58-85 years; 6 men, 3 women) with bleeding and/or deep wall lesions of the GI tract. The OTSC system is composed of an application cap, which is mounted onto the distal tip of the endoscope and a connected releasing mechanism, installed on the handle of the scope. The rotation of the handle allows the release of the clip by a two tube sliding mechanism. RESULTS All applications resulted successful, i.e. haemostasis was achieved, and/or wall defects could be closed. No complication was observed that could be ascribed to the clip itself or to the technique. CONCLUSIONS The OTSC system is a new endoscopic tool for compression of large tissue areas and its indications are nonvaricose bleedings difficult to control and lesions or perforations of the GI tract. The initial clinical use of this clipping device proved to be efficient and effective.

High efficacy of endoscopic submucosal dissection for rectal laterally spreading tumors larger than 3 cm

BACKGROUND Endoscopic submucosal dissection (ESD) was recently developed to allow en bloc resection of early neoplasia of the GI tract, including colorectal neoplasia. The endoscopic technique is technically demanding and not yet standardized, and new devices are needed. OBJECTIVE This study aimed to evaluate the efficacy and safety of a new device that combines the functions of injection and cutting. DESIGN Prospective, pilot, single-arm study. METHODS Consecutive patients with rectal laterally spreading tumors (LSTs) 3 cm or larger unsuitable for en bloc resection were enrolled. ESD was performed with a new device that allows cutting and coagulation as well as a needleless, tissue-selective mucosal and submucosal elevation through an axial water-jet channel. MAIN OUTCOME MEASUREMENT The primary endpoint of the study was the en bloc resection rate achieved with ESD in a Western hospital setting. RESULTS Overall, ESD was attempted in 40 consecutive patients (27 male, mean age 65.3 years) with rectal LSTs larger than 3 cm (72.5% LSTs, nongranular type, 5% depressed type, 22.5% protruding type). The mean lesion size was 46.8 ± 10.9 mm (range 33-80 mm). The mean procedure time was 86.1 ± 35.5 minutes (range 40-190 minutes). The en bloc resection rate was 90% (36/40). In the remaining patients, resection was completed with a piecemeal approach. The rate of curative resection (R0) was 32 of 40 LSTs (80%). Two patients with submucosal invasion were referred for surgery. Perforation occurred in 1 patient (2.5%), which was managed conservatively. Postoperative bleeding occurred in 2 patients (5%) and was treated by endoscopic hemostasis. LIMITATIONS Single-center study with a relatively small number of patients. CONCLUSIONS ESD is a safe and effective method to provide en bloc and curative resection of large rectal LSTs. The operating time and adverse event rate were comparable to those of previously published data from Japanese experts.

The role of K-ras gene mutation analysis in EUS-guided FNA cytology specimens for the differential diagnosis of pancreatic solid masses: a meta-analysis of prospective studies

BACKGROUND Differential diagnosis of pancreatic solid masses with EUS-guided FNA (EUS-FNA) is still challenging in about 15% of cases. Mutation of the K-ras gene is present in over 75% of pancreatic adenocarcinomas (PADC). OBJECTIVE To assess the accuracy of K-ras gene mutation analysis for diagnosing PADC. DESIGN We systematically searched the electronic databases for relevant studies published. Data from selected studies underwent meta-analysis by use of a bivariate model providing a pooled value for sensitivity, specificity, diagnostic odds ratio, and summary receiver operating characteristic curve. SETTING Meta-analysis of 8 prospective studies. PATIENTS Total of 931 patients undergoing EUS-FNA for diagnosis of pancreatic solid masses. INTERVENTION K-ras mutation analysis. MAIN OUTCOME MEASUREMENTS Diagnostic accuracy of K-ras mutation analysis and of combined diagnostic strategy by using EUS-FNA and K-ras mutation analysis in the diagnosis of PADC. RESULTS The pooled sensitivity of EUS-FNA for the differential diagnosis of PADC was 80.6%, and the specificity was 97%. Estimated sensitivity and specificity were 76.8% and 93.3% for K-ras gene analysis, respectively, and 88.7% and 92% for combined EUS-FNA plus K-ras mutation analysis. Overall, K-ras mutation testing applied to cases that were inconclusive by EUS-FNA reduced the false-negative rate by 55.6%, with a false-positive rate of 10.7%. Not repeating EUS-FNA in cases in which mutation testing of the K-ras gene is inconclusive would reduce the repeat-biopsy rate from 12.5% to 6.8%. LIMITATIONS Small number of studies and between-study heterogeneity. CONCLUSION K-ras mutation analysis can be useful in the diagnostic work-up of pancreatic masses, in particular when tissue obtained by EUS-FNA is insufficient, and the diagnosis inconclusive.

Infliximab Therapy Inhibits Inflammation-Induced Angiogenesis in the Mucosa of Patients With Crohn's Disease

OBJECTIVES:Inflammation-driven angiogenesis contributes to the pathogenesis of inflammatory bowel disease (IBD). In line with this, the efficacy of inhibitors of angiogenesis has been demonstrated in experimental models of colitis. Currently, the ability of infliximab, an anti-tumor necrosis factor-α (TNF-α) agent that is highly beneficial in patients with IBD, to affect mucosal angiogenesis in patients with Crohns disease (CD) and ulcerative colitis (UC) is unknown.METHODS:Patients with active CD (n=14) were treated with infliximab for 1 year, and peripheral blood and intestinal mucosa samples were collected before and after treatment. Mucosal angiogenesis was evaluated by CD31 and Ki-67 staining in endoscopic biopsies at baseline (week 0) and at week 54. The release of vascular endothelial growth factor-A (VEGF-A) by cultured mucosal extracts was measured by enzyme-linked immunosorbent assay (ELISA), before and after administration of infliximab, as well as in cultures of human intestinal fibroblasts (HIFs) stimulated with TNF-α in the presence or absence of infliximab. Migration of human intestinal microvascular endothelial cells (HIMECs) was investigated by migration assays.RESULTS:Microvessel density was significantly higher in the mucosa from patients with CD compared with tissue from healthy control individuals. Of the 14 patients, 8 (57%) showed a clinical remission in response to infliximab, which was associated with a significant reduction of microvascular density. Morphometric vessel analysis further confirmed the significant reduction of the area of vascular section after administration of infliximab. Furthermore, the expression levels of the proliferation marker Ki-67 in endothelial cells were significantly reduced after treatment. The mucosal concentration of VEGF-A was also significantly decreased, whereas in vitro exposure of HIF to infliximab virtually abolished TNF-α-induced VEGF-A production. These phenomena did not occur in patients who showed no clinical response to infliximab.CONCLUSIONS:Administration of infliximab downregulates mucosal angiogenesis in patients with CD and restrains production of VEGF-A by mucosal fibroblasts. It is proposed that this ameliorates inflammation-driven angiogenesis in the gut mucosa and contributes to the therapeutic efficacy of blockade of TNF-α.

A new metal stent with a controlled-release system for palliation of malignant dysphagia: a prospective, multicenter study

BACKGROUND Self-expanding metal stents are frequently used for the palliation of malignant dysphagia. Recently, a new stent design, the Evolution stent (Cook Medical, Limerick, Ireland), was developed. The stent has an internal and external silicone coating to resist tissue ingrowth and uncoated dual flanges on both ends to prevent migration. Its controlled-release system may allow full control and precise positioning of the stent. OBJECTIVE To determine the safety and clinical effectiveness of the Evolution stent for the palliation of dysphagia in patients with malignant strictures located in the esophagus (n = 33 [75%]) or gastric cardia (n = 11 [25%]). METHODS All patients who underwent placement of an esophageal Evolution stent from February to December 2008 received follow-up telephone calls 14 days after treatment and thereafter monthly until death. Data on technical and clinical outcome, complications, and recurrent dysphagia were collected. RESULTS A total of 44 patients (32 [73%] men, median age 74 years [range 48-91 years]) were treated with the Evolution stent. The median tumor length was 6 cm (range 1-11 cm). Stent placement was technically successful in 41 patients. Dysphagia improved from a median of 3 (ability to swallow liquids only) to 1 (ability to eat some solid foods) 4 weeks after stent placement. Major complications occurred in 4 (9%) patients, ie, pneumonia (3 patients) and hemorrhage (1 patient). Two (5%) patients died of pneumonia. Minor complications included gastroesophageal reflux and mild retrosternal pain in 11 (25%) and 4 (9%) patients, respectively. Recurrent dysphagia developed in 11 (25%) patients as a result of tissue ingrowth or overgrowth (6 patients; 14%), food impaction (3 patients; 7%), or stent migration (2 patients; 5%). CONCLUSIONS The Evolution stent is safe and effective for the palliation of dysphagia from esophageal and gastric cardia cancer. Randomized trials are needed to compare this device with other stent designs.

A new regimen of bowel preparation for PillCam colon capsule endoscopy: a pilot study.

BACKGROUND Colon capsule endoscopy (CCE) represents a new diagnostic, endoscopic technology for colonic exploration. Current protocols of preparation led to discordant rates of adequate cleansing level or CCE excretion. AIM To evaluate the effect of a new regimen of bowel preparation for CCE on colon cleansing levels and on rate of capsule excretion. STUDY 60 patients were prospectively enrolled. The new regimen of preparation consisted of a split regimen of PEG administration and of a 45 mL dose of sodium phosphate (NaP). Four senna tablets and a low-residue diet were also included. CCE excretion rate, colon cleansing, and accuracy were assessed. RESULTS Forty-six patients were included in the final analysis, 13 patients (22%) being excluded because of preparation protocol deviations and one due to CCE technical failure (2%). At CCE, bowel preparation was rated as good in 78% of patients, fair in 20% and poor in 2%. CCE excretion rate occurred in 83% of patients. CCE sensitivity and specificity for significant findings was 100% and 95%, respectively. CONCLUSIONS The combination of a split-dose of PEG solution with a low dose of NaP boosters resulted in high rates of adequate cleansing level and CCE excretion.

Complications of endoscopic ultrasound fine needle aspiration on pancreatic cystic lesions: Final results from a large prospective multicenter study

BACKGROUND Endoscopic ultrasound-guided fine needle aspiration of pancreatic cystic lesions has been reported to have a higher complication rate than that of solid lesions, but the real complication rate is unknown. Aim of the study was to identify the complication rate of endoscopic ultrasound-guided fine needle aspiration and related risk factors. METHODS Prospective multicenter study at four referral centres. Data were collected from January 2010 to July 2012, searching for all adverse events related to guided fine needle aspiration. All complications occurring up to day 90 were recorded. RESULTS 298 patients (43.9% male, mean age 63.2 ± 15.4 years) underwent endoscopic ultrasound-guided needle aspiration of pancreatic cystic lesions. Mean size was 34.1 ± 9 mm. Adverse events occurred in 18 patients (6%): mild complications in 12/18 (66.6%), and moderate complications in 6/18 (33.3%). Seven were immediate, 6 early, and 5 late. All resolved with medical therapy. CONCLUSIONS Endoscopic ultrasound-guided fine needle aspiration of pancreatic cystic lesions has been found to be associated with a higher complication rate than for solid lesions; however, the risk rate is acceptable considering the complication grade and the important diagnostic role of the technique in the management of pancreatic cystic lesions.

Consensus guidelines on severe acute pancreatitis

This Position Paper contains clinically oriented guidelines by the Italian Association for the Study of the Pancreas (AISP) for the diagnosis and treatment of severe acute pancreatitis. The statements were formulated by three working groups of experts who searched and analysed the most recent literature; a consensus process was then performed using a modified Delphi procedure. The statements provide recommendations on the most appropriate definition of the complications of severe acute pancreatitis, the diagnostic approach and the timing of conservative as well as interventional endoscopic, radiological and surgical treatments.