Fabio Romeo

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.

Safety of cold polypectomy for <10mm polyps at colonoscopy: a prospective multicenter study.

BACKGROUND Cold polypectomy techniques (without electrocautery) by means of biopsy forceps or snare are widely adopted for the removal of subcentimetric polyps. However, few data are available on the safety of this approach. The aim of this study was to assess the safety of cold polypectomy for subcentimetric polyps, as well as the rate of advanced neoplasia in these lesions. PATIENTS AND METHODS In a prospective multicenter trial, consecutive patients with at least one < 10-mm polyp at colonoscopy were prospectively included. All of the < 10-mm polyps detected within the study period were removed by cold polypectomy. The rates of immediate or delayed bleeding and other complications were assessed at 7 and 30 days after cold polypectomy by telephone calls. The rate of advanced histology was also assessed. Predictive variables of postpolypectomy bleeding or advanced neoplasia were identified by multivariate analysis. RESULTS A total of 1015 < 10-mm polyps in 823 patients (15.5 % on antiplatelet agents) were removed. Of these, 822 (81 %) were ≤ 5 mm and 193 (19 %) were 6 - 9 mm. Immediate postpolypectomy bleeding occurred in 18 patients, corresponding to a per-patient and per-polyp bleeding rate of 2.2 % (95 % confidence interval [CI] 1.2 % - 3.2 %) and 1.8 % (95 %CI 1 % - 2.6 %), respectively. Therapy with antiplatelet agents (odds ratio [OR] 4; 95 %CI 1.5 - 10.6) and larger polyp size (OR 2; 95 %CI 1.1 - 6.9) were independent predictors of bleeding. Bleeding was successfully treated by endoscopic hemostasis in all cases and required no further medical intervention. Advanced neoplasia prevalence in polyps ≤ 5 mm was as high as 8.7 %. CONCLUSIONS The results from this study showed the high safety of a cold polypectomy approach for subcentimetric polyps. This was due to the low rate of postpolypectomy bleeding and to the high efficacy of endoscopic hemostasis in its treatment. The high rate of advanced neoplasia in polyps ≤ 5 mm should prompt some caution on the management of these lesions following detection at computed tomography colonography or colon capsule endoscopy.

The role of MAPK in governing lymphocyte adhesion to and migration across the microvasculature in inflammatory bowel disease

Lymphocyte recruitment is a key pathogenic event in inflammatory bowel disease (IBD). Adhesion of T cells to human intestinal microvascular endothelial cells (HIMEC) is mediated by ICAM‐1, VCAM‐1 and fractalkine (FKN), but the signaling molecules that orchestrate this process have yet to be identified. Because MAPK play an important role in the response of many cell types to pro‐inflammatory stimuli, we assessed the functional role of p38 MAPK, p42/44 MAPK and JNK in the regulation of lymphocyte adhesion to and chemotaxis across the microvasculature in IBD. We found that the MAPK were phosphorylated in the bowel microvasculature and human intestinal fibroblasts of patients with IBD but not of healthy individuals. Stimulation of HIMEC with TNF‐α triggered phosphorylation of the MAPK, and up‐regulation of VCAM‐1, FKN and ICAM‐1. Blockade of p38 decreased the expression of all MAPK by 50% (p<0.01), whereas inhibition of p42/44 decreased the expression of ICAM‐1 and FKN by 50% (p<0.01). Treatment of human intestinal fibroblasts with TNF‐α elicited production of IL‐8 and MCP‐1, which was reduced (p<0.05) by blockade of p38 and p42/44. Finally, blockade of p38 and p42/44 reduced lymphocyte adhesion to (p<0.05) and transmigration across (p<0.05) HIMEC monolayers. These findings suggest a critical role for MAPK in governing lymphocyte influx into the gut in IBD patients, and their blockade may offer a molecular target for blockade of leukocyte recruitment to the intestine.

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.

Accuracy of narrow-band imaging in predicting colonoscopy surveillance intervals and histology of distal diminutive polyps: results from a multicenter, prospective trial

BACKGROUND In vivo prediction of colorectal polyp histology by narrow-band imaging (NBI) could potentially avoid post-polypectomy histologic examination or resection of diminutive lesions, thereby reducing costs and risk. OBJECTIVE To assess whether NBI is able to predict colonoscopy surveillance intervals and histology of distal diminutive polyps according to American Society for Gastrointestinal Endoscopy (ASGE) criteria. DESIGN Prospective, multicenter study. SETTING Five endoscopic centers. PATIENTS Consecutive patients undergoing colonoscopy in 5 centers were included. INTERVENTION Participating endoscopists were required to pass a before-study qualifying examination. Histology of polyps that were <10 mm was predicted at NBI and assigned a designation of high or low confidence. MAIN OUTCOME MEASUREMENTS Accuracy of high-confidence NBI prediction for polyps ≤5 mm in predicting surveillance intervals and negative predictive value (NPV) for adenomatous histology in the rectosigmoid colon were compared with the ASGE thresholds (90% agreement, 90% NPV). RESULTS A total of 278 patients (mean age, 63 years; 58% male) were enrolled. At colonoscopy, 574 (97.3%) polyps <10 mm (429 ≤5 mm, 60% adenomatous) were retrieved for histologic analysis. Sensitivity, specificity, positive and negative predictive values, and accuracy of high confidence-NBI predictions for adenomatous histology in lesions ≤5 mm were 90%, 88%, 89%, 89%, and 89%, respectively. High-confidence characterization of polyps ≤5 mm predicted the correct surveillance interval in 92% to 99% of cases, according to the American and European guidelines. NPV of high-confidence NBI for adenomatous histology for the rectosigmoid colon lesions ≤5 mm was 92%. LIMITATIONS Only experienced endoscopists were included. CONCLUSION High-confidence prediction of histology for polyps ≤5 mm appears to be sufficiently accurate to avoid post-polypectomy histologic examination of the resected lesions as well as to allow rectosigmoid hyperplastic polyps to be left in place without resection. ( CLINICAL TRIAL REGISTRATION NUMBER NCT01675752.).

Endoscopic flexible treatment of Zenker's diverticulum: A modification of the needle-knife technique

BACKGROUND AND STUDY AIM Endoscopic treatment of Zenkers diverticulum has been successfully reported over the last 10 years using different approaches. The hook-knife is a new device originally developed for endoscopic submucosal dissection procedures. This study aimed to investigate the safety and efficacy of endoscopic myotomy performed with the hook-knife. PATIENTS AND METHOD From July 2005, 32 consecutive patients (23-male, mean age 74.8 years) with dysphagia secondary to the presence of Zenkers diverticulum were prospectively enrolled. Myotomy was performed using a straight-end transparent hood to the tip of the scope and the hook-knife for the incision of the bridge between the Zenkers diverticulum and the esophagus. Clinical outcome was evaluated assigning a dysphagia symptom score from 0 (symptoms absent) to 4 (inability to swallow saliva). RESULTS General anesthesia was used in 4 patients, deep sedation with propofol in 23 patients, while midazolam was used in 5 patients. The mean procedural time was 28 minutes. Complications occurred in 2 patients (6.25 %). At 1 month follow-up, the mean dysphagia score was significantly improved from 2.9 to 0.6 ( P < 0.001) with 87.5 % of patients free of symptoms and 4 patients with dysphagia that was persistent but milder than before the treatment. Three of these 4 patients underwent a successful second endoscopic treatment with complete relief of dysphagia; one was not re-treated because of advanced age (92 years). During the follow-up period (23.87 +/- 9.6 months), 2 patients developed dysphagia recurrence. The overall success rate was 90.6 %. CONCLUSIONS Diverticulectomy with a flexible scope and the hook-knife may represent a safe and effective alternative treatment for patients with Zenkers diverticulum.

Balanced propofol sedation administered by nonanesthesiologists: The first Italian experience

AIM To assess the efficacy and safety of a balanced approach using midazolam in combination with propofol, administered by non-anesthesiologists, in a large series of diagnostic colonoscopies. METHODS Consecutive patients undergoing diagnostic colonoscopy were sedated with a single dose of midazolam (0.05 mg/kg) and low-dose propofol (starter bolus of 0.5 mg/kg and repeated boluses of 10 to 20 mg). Induction time and deepest level of sedation, adverse and serious adverse events, as well as recovery times, were prospectively assessed. Cecal intubation and adenoma detection rates were also collected. RESULTS Overall, 1593 eligible patients were included. The median dose of propofol administered was 70 mg (range: 40-120 mg), and the median dose of midazolam was 2.3 mg (range: 2-4 mg). Median induction time of sedation was 3 min (range: 1-4 min), and median recovery time was 23 min (range: 10-40 min). A moderate level of sedation was achieved in 1561 (98%) patients, whilst a deep sedation occurred in 32 (2%) cases. Transient oxygen desaturation requiring further oxygen supplementation occurred in 8 (0.46%; 95% CI: 0.2%-0.8%) patients. No serious adverse event was observed. Cecal intubation and adenoma detection rates were 93.5% and 23.4% (27.8% for male and 18.5% for female, subjects), respectively. CONCLUSION A balanced sedation protocol provided a minimalization of the dose of propofol needed to target a moderate sedation for colonoscopy, resulting in a high safety profile for non-anesthesiologist propofol sedation.

Su1540 Self-Expandable Biodegradable Stent in the Management of Refractory Benign Colorectal Strictures: Preliminary Results From a Pilot Study

Su1540 Self-Expandable Biodegradable Stent in the Management of Refractory Benign Colorectal Strictures: Preliminary Results From a Pilot Study Alessandro Repici, Giacomo Rando, Fabio Romeo, Nico Pagano, Alessandra Carlino, Eva Vitetta, Gabriele Delconte, Giuseppe Strangio, Silvio Danese, Daniel D. Ferreira, Alberto Malesci Servizio di Endoscopia Digestiva, IRCCS Istituto Clinico Humanitas, Rozzano (MI), Italy Self-expanding metal stents (SEMS) are an established treatment for palliation of malignant colorectal strictures and as a bridge to surgery for acute malignant colonic obstruction. Patients with benign colonic strictures may potentially benefit from stent placement, but little and controversial data exist for this indication. Aim of this study was to evaluate the efficacy and safety of biodegradable stents in the management of benign refractory colorectal strictures. A single center pilot study including patients with benign strictures located within 25 from anal verge refractory to mechanical or pneumatic dilation (at least 3 sessions). Exclusion criteria were: presence of concomitant fistula, suspicion of malignancy, diverticulosis, previous stent placment and stricture located too close to the anus ( 5cm). Outcome was evaluated clinically and as ability to pass through the stricture with a regular size colonoscope. Data were prospectively collected in an electronic database and follow-up was scheduled with endoscopic control after 14, 30, 90 days and afterwards at monthly interval by telephone interview. The stent used was an esophageal biodegradable stent (Ella, Czech Rep), in two different size 25 and 30 mm. Stent was placed under fluoroscopic and endoscopic control. Results: 11 consecutive patients (8M/3F, mean age 58.8y) were enrolled from September 2009. The etiologies of the stricture were: postsurgical anastomotic (n 8), radiation-induced (n 2), and Crohn’s (n 1) disease. Mean stricture length was 2.4 cm (2-4 cm). Stent placement was technically successful for all patients. No perforation occurred in the present series. Stent migration occurred in 4 patients after 4 days, 10 days, 14 days and 3 weeks respectively. One of these patients developed an acute obstruction after stent migration and underwent emergency surgery. Two patients are under periodic dilation and one was retreated with a second biodegradable stent. One patient presented with acute bowel occlusion due to fecal impaction 2 months after stent placement and was successfully treated by endoscopy. Mean follow-up was 7.5 months (range 4-14 months). Among the 7 patients who maintained the stent until its complete degradation, 5 remained asymptomatic and didn’t develop stricture recurrence. Two patients (one with radiation-induced and one with post-surgical stricture) developed symptomatic stricture recurrence and are currently treated with periodic dilation. Placement of biodegradable stent may represent a potential therapeutic alternative in patients with refractory colorectal strictures. High migration rate (36.3%) is a major drawback of this approach. The development of dedicated biodegradable colorectal stent (with anti-migration design) which better fit the colorectal anatomy could help in reducing the migration rate.