The Cooperative Italian FLIN Study Group: prevalence and clinico-pathological features of colorectal laterally spreading tumors.

BACKGROUND AND STUDY AIMS: Laterally spreading tumors (LSTs) are increasingly recognized as important precursors of colorectal carcinoma. The clinical behavior of these large nonpolypoid lesions is still uncertain. The aim of the present study was to assess prevalence and clinico-pathological features of LSTs in a large Italian cohort of patients. METHODS: The study was a subgroup analysis of a large database of patients undergoing total colonoscopy. The database originated from a multicenter cross-sectional observational study involving 80 centers throughout Italy. RESULTS: Data from 27,400 total colonoscopies were analyzed. Precancerous lesions were detected in 5609 patients. Of these, LSTs were identified in 254 patients (4.5%; 95% confidence interval [CI] 3.5-6.2). Granular-type LSTs (G-LSTs) accounted for 83% of the cases (211/254). LSTs were predominant in the proximal colon (154, 60.6%). A total 231 lesions were endoscopically removed, with histology being available for 242. Neoplasia was confirmed in 225 lesions (93.4%) (143 low grade adenoma, 76 high grade adenoma, and six submucosal cancer). The six cases of submucosally invasive carcinoma were diagnosed in five G-LST and one nongranular LST (NG-LST). The risk of containing advanced histology was not increased in G-LST compared with NG-LST (odds ratio [OR] 1.55, 95%CI 0.73-3.27); it was significantly higher in lesions with large nodules (OR 3.09, 95%CI 1.05-9.04; P = 0.041) or depressed surface (OR 4.27, 95%CI 1.24-14.61; P = 0.021). CONCLUSIONS: LSTs represent approximately 5% of all precancerous colorectal lesions in the Italian population and are prevalent in the proximal colon. These lesions are no more likely to harbor advanced histology than similar-sized polypoid lesions. Large nodularity or depressed surface are risk factors for advanced histology.

How to predict a high rate of inappropriateness for upper endoscopy in an endoscopic centre?

BACKGROUND: Inappropriateness of upper endoscopy (EGD) indication causes decreased diagnostic yield. Our aim of was to identify predictors of appropriateness rate for EGD among endoscopic centres. METHODS: A post-hoc analysis of two multicentre cross-sectional studies, including 6270 and 8252 patients consecutively referred to EGD in 44 (group A) and 55 (group B) endoscopic Italian centres in 2003 and 2007, respectively, was performed. A multiple forward stepwise regression was applied to group A, and independently validated in group B. A <70% threshold was adopted to define inadequate appropriateness rate clustered by centre. RESULTS: discrete variability of clustered appropriateness rates among the 44 group A centres was observed (median: 77%; range: 41-97%), and a <70% appropriateness rate was detected in 11 (25%). Independent predictors of centre appropriateness rate were: percentage of patients referred by general practitioners (GP), rate of urgent examinations, prevalence of relevant diseases, and academic status. For group B, sensitivity, specificity and area under receiver operating characteristic curve of the model in detecting centres with a <70% appropriateness rate were 54%, 93% and 0.72, respectively. CONCLUSIONS: A simple predictive rule, based on rate of patients referred by GPs, rate of urgent examinations, prevalence of relevant diseases and academic status, identified a small subset of centres characterised by a high rate of inappropriateness. These centres may be presumed to obtain the largest benefit from targeted educational programs.

Prevalence of nonpolypoid colorectal neoplasia: an Italian multicenter observational study.

BACKGROUND AND STUDY AIM: The aim of this study was to assess the prevalence of nonpolypoid lesions (NPLs) in Italy and their risk of containing neoplasia or advanced histology. PATIENTS AND METHODS: This was a multicenter cross-sectional observational study on consecutive patients undergoing total colonoscopy over a 3-month period in 80 Italian centers. RESULTS: In all, 27,400 total colonoscopies were analyzed. Cancer was diagnosed in 801 patients (2.9 %). A total of 6553 precancerous lesions were detected in 5609 patients. Of these, 4154 patients (74.1 %) had polypoid lesions and 1455 patients (25.9 %) had NPLs. Therefore, the prevalence of NPLs was 5.3 % (95 %CI 5.0 - 5.6). NPLs larger than 10 mm were detected in 254 patients (17.5 %). NPLs were more predominant in the proximal colon (OR 2.92, 95 %CI 2.56 - 3.43; P < 0.0001 vs. polypoid lesions). Neoplastic tissue was diagnosed in 79.0 % and advanced histology (high-grade intraepithelial neoplasia or more) in 20.9 % of resected lesions. The risk of advanced histology was similar for polypoid and nonpolypoid lesions when adjusted for size. Depressed lesions had the highest risk of advanced histology (OR 10.56, 95 %CI 6.02 - 18.55; P < 0.0000 vs. flat-elevated). Age was an independent predictor of both neoplasia and advanced histology ( P = 0.0001). CONCLUSIONS: NPLs are relatively common in the Italian population, with a prevalence similar to that in other Western series. NPLs are not more aggressive than polypoid lesions, except for those with depressed morphology.

A randomised study of hydro-jet vs. needle injection for lifting colorectal lesions prior to endoscopic resection.

BACKGROUND: Submucosal lifting of lesions prior to endoscopic resection is crucial to reduce complications and improve the technical feasibility of the procedure. AIM: To compare a self-assembled hydro-jet system vs. standard needle injection for tissue elevation prior to endoscopic resection of colorectal lesions. METHODS: Randomised study performed at a single tertiary care institution. Consecutive patients with colonoscopic diagnosis of sessile polyps or non-polypoid lesions >5 mm or laterally spreading tumours. OUTCOME MEASURES: successful elevation, time to proper elevation, completeness of excision, cautery damage, and general histological diagnostic quality (blinded pathologic assessment). RESULTS: 79 patients were randomised to hydro-jet (40 patients, group A) and needle (39 patients, group B) elevation. Successful elevation was achieved in 97.5% and 94.8%, respectively. Time to proper elevation was 8+/-5 s vs. 18+/-3 s (p<0.05). In group A, histology showed selective accumulation of fluid in the submucosa with intact collagen fibres. Damage to muscularis mucosa was never noted in the specimens of group A and in 7 cases of group B (p<0.01). Artefacts from "cautery effect" were very limited. Radial margins of resection could be adequately evaluated in all cases and were negative. CONCLUSIONS: The hydro-jet system is as effective and safe as standard needle injection for tissue elevation prior to endoscopic resection of colorectal lesions, but it is significantly faster.

Blue rubber bleb nevus syndrome.

UNLABELLED: Blue Rubber Bleb Nevus Syndrome (BRBNS) is a rare condition characterized by multiple venous malformations involving the skin and internal organs. The gastrointestinal tract is always involved and intestinal haemorrhage is the most frequent clinical manifestation associated with iron deficiency anaemia. We describe a 10-year-old girl who, since birth, presented numerous venous malformations all over her body and a lymphangioma in the right leg. At the age of 5 years, she also had a severe episode of gastric bleeding requiring a blood transfusion. From this episode, she is suffering from chronic anaemia and this is the reason for admission into our hospital. The endoscopic examination of the gastrointestinal tract revealed multiple giant venous malformations in the oesophagus, stomach, duodenum and in all visible sections of the colon. Endoscopy is the gold standard technique for the diagnosis of BRBNS with GI lesions and also allows immediate therapeutic measures such as argon plasma coagulation, laser photocoagulation, sclerotherapy or band ligation. In addition, pharmacological treatments based on corticosteroids, interferon alfa, vincristine or octreotide have been described for BRBNS. CONCLUSION: Blue Rubber Bleb Nevus Syndrome is a congenital cutaneous and gastrointestinal haemangiomatosis. Its morbidity and mortality depends on involvement of visceral organs and particularly on GI bleeding. The treatment is based on pharmacological or surgical therapy. Overall, the most important step is the follow-up to the presence and the evolution of GI lesions and the possible bleeding.

Degree of concordance between double-balloon enteroscopy and capsule endoscopy in obscure gastrointestinal bleeding: a multicenter study.

BACKGROUND AND STUDY AIMS: Capsule endoscopy is considered the diagnostic procedure of choice in patients with obscure gastrointestinal bleeding (OGIB). Double-balloon endoscopy (DBE) offers both diagnostic and therapeutic potential, but is invasive, complex, and time-consuming. The aim was to evaluate diagnostic agreement between capsule endoscopy and DBE in patients with OGIB, and secondarily the diagnostic gain of DBE when capsule endoscopy detected only blood or clots in the small-bowel lumen. METHODS: Multicenter prospective study carried out at six institutions in Italy. RESULTS: 193 patients (119 men, mean age 61.6 +/- 16.2) first underwent capsule endoscopy and then DBE. The most frequent positive findings at capsule endoscopy were vascular lesions (74 patients, 38.3 %), blood or clot in the lumen (34, 17.6 %), and tumor mass (20, 10.4 %). The most frequent findings at DBE were vascular lesions (72 patients, 37.3 %), neoplasia (30, 15.5 %) and ulcers/inflammatory lesions (12, 6.2 %). Overall kappa coefficient was 0.46 (95 %CI 0.38 - 0.54), with maximum concordance for vascular (0.72 [95 %CI 0.59 - 0.84]) and inflammatory (0.78 [0.58 - 0.99]) lesions and minimum for polyps (0.46 [0.16 - 0.80]). Blood in the lumen was the only positive finding at capsule endoscopy in 34 cases; of these, 12 had negative DBE findings whereas 10 had vascular lesions, 6 neoplasia, 1 ulcer, and 5 diverticula. CONCLUSION: Capsule endoscopy and DBE have good agreement for vascular and inflammatory lesions but not for polyps or neoplasia. DBE provides valuable adjunctive information, particularly in patients with neoplasia or polyp at capsule endoscopy. DBE clarified the origin of bleeding in two-thirds of patients with capsule endoscopy showing only blood in the lumen.

Acrylate glue injection for acutely bleeding oesophageal varices: A prospective cohort study.

BACKGROUND: Acrylate glue injection is seldom performed in patients with bleeding oesophageal varices. AIM: To assess efficacy and safety of acrylate glue injection in patients with bleeding oesophageal varices, as well as the impact of this technique on subsequent variceal ligation. METHODS: Prospective study on 133 consecutive cirrhotic patients treated by intravariceal injection of undiluted N-butyl-2-cyanoacrylate into the bleeding varix. Outcome measures were initial haemostasis, recurrent bleeding, complications and mortality at 6 weeks. RESULTS: 52 patients were actively bleeding at endoscopy and 81 showed stigmata of recent haemorrhage. Initial haemostasis was achieved in 49/52 active bleeders (94.2% [95% CI 85.1-98.5]). Overall, early recurrent bleeding occurred in 7 patients (5.2% [95% CI 2.3-10.1]). No major procedure-related complication was recorded. At 6 weeks, death occurred in 11 patients, with an overall bleeding-related mortality of 8.2% [95% CI 5.8-15.3]. Mortality was higher in active (15.4% [95% CI 6.9-28.1]) than non-active bleeders (3.7% [95% CI 0.8-10.4], OR 4.7 [95% CI 1.05-28.7], p=0.02). Of those surviving the first bleeding episode, 112 patients subsequently underwent ligation. No technical difficulties were encountered in performing the banding procedure which was successfully completed in all cases. CONCLUSIONS: Emergency injection of acrylate glue is safe and effective for the treatment of acute bleeding oesophageal varices and does not hamper subsequent variceal ligation.

Endocytoscopy can identify dysplasia in aberrant crypt foci of the colorectum: a prospective in vivo study.

BACKGROUND AND STUDY AIM: A catheter-type endocytoscope has recently been developed that is able to provide in vivo cellular images of gastrointestinal mucosa. Aberrant crypt foci (ACF) represent the earliest precursor of colorectal cancer featuring the dysplasia-carcinoma sequence. The aim of the current study was to assess the potential of the endocytoscopy system (ECS) in the "in vivo" detection of dysplasia in colorectal ACF. PATIENTS AND METHODS: Consecutive patients with colorectal ACF were studied with endocytoscopy. Blinded endoscopic and histological assessments were obtained. Lesions were excised en bloc for histology. RESULTS: A total of 48 colorectal lesions were examined in 41 patients. The mean duration of the ECS procedure was 44 +/- 12 minutes (range 31 - 62 minutes). The quality of ECS images was rated as good in 39/48, medium in six, and poor in three (6.2 %). It was possible to observe lesions at the cellular level and evaluate both cellular and structural atypia in vivo. In normal mucosa, crypts had preserved individuality and round-shaped contours. Nuclei were located at the basal third of the crypt in a single line, and the lumen was circular. In dysplastic ACF, crypt contours were polygonal, cell nuclei were elongated with pseudostratification toward the luminal half of the crypt and irregularly arranged, and the lumen was linear. In all, 23 endocytoscopic images were labeled as dysplastic and 25 as nondysplastic. Histology confirmed low-grade dysplasia in 21/23 cases (91.4 % sensitivity). Absence of dysplasia was confirmed in the remaining 25 cases (100 % specificity). Interobserver agreement between trained endoscopist and pathologist was good (wK 0.68; 95 % CI 0.59 - 0.78). CONCLUSIONS: Endocytoscopy provides real-time histological images in vivo, with clear visualization of cellular details and features of dysplasia in colorectal ACF.

Successful endoscopic treatment of Bouveret's syndrome by mechanical lithotripsy.

Gastric outlet obstruction secondary to the impaction of large biliary stones into the duodenum (Bouveret's syndrome) is a well-known complication of biliary lithiasis, most often requiring surgical intervention. We report a case of successful endoscopic removal of a large stone impacted in the duodenal bulb by means of mechanical lithotripsy.

Diagnostic value of endoscopic markers for celiac disease in adults: a multicentre prospective Italian study.

AIM: Some endoscopic features of duodenal mucosa are marker of mucosal injury, the most common cause being celiac disease (CD). The aim of this study was to prospectively assess the diagnostic value of the endoscopic markers for the diagnosis of CD in the adult population undergoing routine upper endoscopy. METHODS: This was a prospective multicenter study conducted at 37 Italian endoscopic centers. A total of 509 consecutive patients submitted to routine upper endoscopy who presented one or more of following endoscopic markers were included: 1) mucosal mosaic pattern in the bulb and/or descending duodenum (DD); 2) nodularity in the bulb and/or DD; 3) scalloping of Kerkring's folds; 4) reduction in the number or absence of folds in the DD. 4 biopsies samples were taken from descending duodenum. In patients with histological findings consistent with CD, according to Oberhuber classification, sierologic test (EMA, tTGA) were performed for confirm the diagnosis. RESULTS: At endoscopy, 249 patients showed an isolated marker; 260 subjects showed a coexistence of more than one marker; 369 patients (72.5%) presented mucosal lesions at histological examination and in 347 of these patients the diagnosis of CD was confirmed by serologic markers (94.0%). For 10 patients the diagnosis remained uncertain because of negative sierology and exclusion of other other cause of mucosal lesions. The diagnosis of CD was made in 61.3% patients who showed the mosaic pattern, in 65.7% of patients with nodular mucosa, in 64.4% of patients with scalloping of folds, in 40.2% of patients with reduction of folds, and in 61.5% of patients with loss of folds and in 83.6% of patients who showed the coexistence of more than one marker. The endoscopic markers overall had a PPV of 68% for the diagnosis of CD; the markers that singularly have demonstrated a higher correlation with CD are: mosaic mucosa of DD (PPV 65.0%), nodular mucosa of the bulb and DD (PPV 75.5%), and scalloping of folds (PPV 64.4%). CONCLUSION: The study confirms the important role of endoscopy in the diagnostic process of CD not only for the bioptic sampling in patients with clinical suspicion of CD, but especially for the opportunity to evaluate alterations of the duodenal mucosa suggestive of CD in the general population and, consequently, to identify those patients who should undergo a duodenal biopsy.

Reflux oesophagitis in Italy (Diomede project).

AIMS: A multicentric observational study was performed to update the available information on reflux oesophagitis in Italy. METHODS: In phase I, the number and severity of reflux oesophagitis diagnosed in 1 year (2003) were reported together with the associated endoscopic findings. In phase II, oesophagitis patients consecutively referred in a 3-month period were analysed. A multivariate analysis was used to identify the risk factors for severe oesophagitis. RESULTS: 253,992 upper endoscopies were collected. The overall prevalence of oesophagitis was 14.8% and the endoscopic findings associated with oesophagitis were hiatus hernia (46.3%), duodenal ulcer (10.7%), gastric ulcer (3.6%) and Barrett's oesophagus (2.9%). In phase II, 1542 reflux oesophagitis patients were analysed (60.3% males; mean age 50.7 +/-16.6 years). Only 53.4% of patients reported heartburn and/or regurgitation as main complaint. Severe symptoms, age > 50 years, hiatus hernia and male gender were identified as independent predictors of severe oesophagitis. CONCLUSIONS: Oesophagitis is the most frequent among the peptic diseases of the upper gastro-intestinal tract. Only half of the oesophagitis patients reported typical reflux symptoms as dominant. Advanced age, male gender, severe symptoms and hiatus hernia were independent risk factors for severe disease.

Endoscopic palliation of malignant obstructive jaundice: an evidence-based review.

Endoscopic stent insertion is considered the method of choice for palliative treatment of malignant biliary obstruction. Nonetheless, relevant studies are often underpowered or outdated and do not compare actual surgical outcomes with latest stent technology. Purpose of this review was to assess, with an evidence-based methodology, the role of endoscopic versus surgical palliation of patients with malignant obstructive jaundice with special reference to clinical effectiveness, safety aspects and economic outcomes.

Predictive value of magnification chromoendoscopy for diagnosing invasive neoplasia in nonpolypoid colorectal lesions and stratifying patients for endoscopic resection or surgery.

BACKGROUND AND STUDY AIMS: In nonpolypoid colorectal lesions, the presence of irregular, distorted glands in the colon (a disrupted crypt pattern) on magnification chromoendoscopy (MCE) is strongly associated with submucosal invasive cancer. The aim of the present study was to evaluate the ability of MCE to differentiate between an invasive crypt pattern and a noninvasive crypt pattern, including nonneoplastic lesions, and to assess the ability of this MCE classification to predict invasiveness and allow patients to be selected for endoscopic resection or surgical resection. PATIENTS AND METHODS: In a prospective study including 1560 colonoscopies, 153 flat or depressed colorectal lesions were evaluated with MCE among 534 colorectal lesions; the remainder had a polypoid appearance. The pit pattern was classified as nonneoplastic (type II) or neoplastic (types III - V), and the latter was subdivided into noninvasive (types III or IV) or submucosally invasive (type V). Lesions with a nonneoplastic and noninvasive neoplastic appearance were resected endoscopically if technically feasible, whereas those with a type V pattern were resected surgically. The resection specimens were analyzed histologically in relation to the Vienna classification. RESULTS: Using this management strategy based on the pit pattern, 86 % (n = 70) of the type II lesions were hyperplastic; the remaining 11 had low-grade intraepithelial neoplasia. Type III and IV lesions (n = 58) represented either low-grade or high-grade intraepithelial neoplasia in 95 % of the cases. Three patients had sm1 (n = 2) or sm2/3 invasive cancers. Among the patients with type V lesions (n = 14), 11 had invasive cancers (four sm1 and seven sm2/3). Endoscopic differentiation based on the pit pattern thus had a positive predictive value (PPV) of 86 % and a negative predictive value of 96 % for distinguishing between nonneoplastic and neoplastic lesions. The pit pattern criteria for distinguishing between invasive and noninvasive neoplasia (including nonneoplastic lesions), and hence the choice between endoscopic and surgical resection, had a PPV of 79 % and a NPV of 98 %. Excluding nonneoplastic lesions, the NPV would be 95 %. CONCLUSIONS: The endoscopic pit pattern on MCE has only a moderate predictive value for nonneoplastic lesions, so that leaving these flat hyperplastic lesions in place on the basis of the endoscopic magnification appearance alone cannot be generally recommended. However, MCE has a good predictive value for guiding management toward either endoscopic resection (if technically feasible) or surgical resection.

Management of gastro-oesophageal reflux disease: role of proton pump inhibitor test and upper gastro-intestinal endoscopy.

Authors report the available scientific evidence on the role of proton pump inhibitors and upper gastro-intestinal endoscopy in the management of patients with gastro-oesophageal reflux disease. Relative indications, advantages and pitfalls of various diagnostic and therapeutic strategies for cost-effective management of this condition are discussed. The most recent evidence-based guidelines are outlined.

Endoscopic treatment of gastro-oesophageal reflux disease.

Gastro-oesophageal reflux disease is a common chronic disorder which has a severe effect on the patient's quality of life. In view of the high cost of medical therapy and the limitations of surgery, a variety of endoscopic techniques have been developed for the treatment of this condition, and these have shown apparently encouraging results, at least in the short- term. However, several inconsistencies have emerged between the efficacy of endoscopic treatment in improving symptoms and quality of life and a lack of improvement of objective parameters. Controlled studies are urgently needed in order to clarify the potential of endoscopic therapy. Currently, the use of endoscopic treatment should be limited to clinical trials.

Meta-analysis: capsule enteroscopy vs. conventional modalities in diagnosis of small bowel diseases.

BACKGROUND: Prospective trials support the role of capsule enteroscopy as an improvement in diagnosing mucosal lesions in the small bowel. AIM: To determine the diagnostic yield and safety of capsule enteroscopy vs. alternative diagnostic modalities (such as push enteroscopy, small bowel follow-through or enteroclysis) in patients with small bowel diseases. METHODS: A search for prospective studies comparing capsule enteroscopy vs. other diagnostic tests in adults was performed between 1966 and 2005. Selected articles were included in a meta-analysis. Three analyses were run separately, all included studies and studies having occult gastrointestinal bleeding or Crohn's disease as main outcome. RESULTS: Seventeen studies (526 patients) met inclusion criteria. The rate difference (i.e. the absolute pooled difference in the rate of positive findings) between capsule enteroscopy and alternative modalities for small bowel disease was 41% (95% CI 35.6-45.9); 37% (95% CI 29.6-44.1) for occult gastrointestinal bleeding; and 45% (95% CI 30.9-58.0) for Crohn's disease. Failure to visualize the caecum occurred in 13%, significantly more often in occult bleeders (17%) than in patients with Crohn's disease (8%) (P < 0.006). Adverse events were recorded in 29 patients (6%). Capsule retention was more frequent in patients with Crohn's disease (3% vs. 1%, OR 4.37). CONCLUSIONS: Capsule enteroscopy proved significantly superior to push enteroscopy and small bowel radiology in the diagnosis of ileal diseases. Capsule enteroscopy is safe, though prior radiology is still necessary to rule out small bowel strictures in patients with known or suspected Crohn's disease.