Luigi Familiari

Risk factors for post-ERCP pancreatitis in high- and low-volume centers and among expert and non-expert operators: a prospective multicenter study.

OBJECTIVES:Prospective studies have identified a number of patient- and procedure-related independent risk factors for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis, with different conclusions, so various questions are still open. The endoscopists expertise, case volume, and case mix can all significantly influence the outcome of ERCP procedures, but have been investigated little to date.METHODS:We identified patient- and procedure-related risk factors for post-ERCP pancreatitis and the impact of the endoscopists experience and the centers case volume, using univariate and multivariate analysis, in a multicenter, prospective study involving low- and high-volume centers, over a 6-month period.RESULTS:A total of 3,635 ERCP procedures were included; 2,838 (78%) ERCPs were performed in the 11 high-volume centers (median 257 each) and 797 in the 10 low-volume centers (median 45 each). Overall, 3,331 ERCPs were carried out by expert operators and 304 by less-skilled operators. There were significantly more grade 3 difficulty procedures in high-volume centers than in low-volume ones (P<0.0001). Post-ERCP pancreatitis occurred in 137 patients (3.8%); the rates did not differ between high- and low-volume centers (3.9% vs. 3.1%) and expert and non-expert operators (3.8% vs. 5.5%). However, in high-volume centers, there were 25% more patients with patient- and procedure-related risk factors, and the pancreatitis rate was one-third higher among non-expert operators. Univariate analysis found a significant association with pancreatitis for history of acute pancreatitis, either non-ERCP- or ERCP-related and recurrent, young age, absence of bile duct stones, and biliary pain among patient-related risk factors, and >10 attempts to cannulate the Vaters papilla, pancreatic duct cannulation, contrast injection of the pancreatic ductal system, pre-cut technique, and pancreatic sphincterotomy, among procedure-related risk factors. Multivariate analysis also showed that a history of post-ERCP pancreatitis, biliary pain, >10 attempts to cannulate the Vaters papilla, main pancreatic duct cannulation, and pre-cut technique were significantly associated with the complication.CONCLUSIONS:A history of pancreatitis among patient-related factors, and multiple attempts at cannulation among procedure-related factors, were associated with the highest rates of post-ERCP pancreatitis. Pre-cut sphincterotomy, although identified as another significant risk factor, appeared safer when done early (fewer than 10 attempts at cannulating), compared with repeated multiple cannulation. The risk of post-ERCP pancreatitis was not associated with the case volume of either the single endoscopist or the center; however, high-volume centers treated a larger proportion of patients at high risk of pancreatitis and did a significantly greater number of difficult procedures.

IL-1β Converting Enzyme Is a Target for Nitric Oxide-Releasing Aspirin: New Insights in the Antiinflammatory Mechanism of Nitric Oxide-Releasing Nonsteroidal Antiinflammatory Drugs

Caspase-1, the IL-1β converting enzyme (ICE), is required for intracellular processing/maturation of IL-1β and IL-18. NO releasing nonsteroidal antiinflammatory drugs (NSAIDs) are a new class of NSAID derivatives that spare the gastric mucosa. Here, we tested the hypothesis that NCX-4016, a NO-aspirin derivative, inhibits proinflammatory cytokine release from endotoxin (LPS)-challenged monocytes. Our results demonstrated that exposing LPS-stimulated human monocytes to NCX-4016 resulted in a 40–80% inhibition of IL-1β, IL-8, IL-12, IL-18, IFN-γ, and TNF-α release with an EC50 of 10–20 μM for IL-1β and IL-18. Incubating LPS-primed monocytes with NCX-4016 resulted in intracellular NO formation as assessed by measuring nitrite/nitrate, intracellular cGMP concentration, and intracellular NO formation. Exposing LPS-stimulated monocytes to aspirin or celecoxib caused a 90% inhibition of prostaglandin E2 generation but had no effect on cytokine release. NCX-4016, similar to the NO donor S-nitroso-N-acetyl-d-l-penicillamine, inhibited caspase-1 activity with an EC50 of ≈20 μM. The inhibition of caspase-1 by NCX-4016 was reversible by the addition of DTT, which is consistent with S-nitrosylation as the mechanism of caspase-1 inhibition. NCX-4016, but not aspirin, prevented ICE activation as measured by assessing the release of ICE p20 subunit. IL-18 immunoneutralization resulted in a 60–80% reduction of IL-1β, IL-8, IFN-γ, and TNF-α release from LPS-stimulated monocytes. Taken together, these data indicate that incubating human monocytes with NCX-4016 causes intracellular NO formation and suppresses IL-1β and IL-18 processing by inhibiting caspase-1 activity. Caspase-1 inhibition is a new, cycloxygenase-independent antiinflammatory mechanism of NO-aspirin.

Endoscopic mucosal resection for large and giant sessile and flat colorectal polyps: a single-center experience with long-term follow-up

BACKGROUND AND STUDY AIMS This study examines efficacy, outcome, and complications of endoscopic mucosal resection (EMR) for large (> or = 20 mm) and giant (> or = 40 mm) sessile and flat colorectal polyps. PATIENTS AND METHODS All EMRs carried out at our institution over a 9-year period, for large and giant sessile and flat colorectal polyps with an intensive and regular follow-up were evaluated. The rate of en bloc and piecemeal resection, complications, and recurrence were analyzed. RESULTS A total of 148 polyps were resected in 148 patients. There were 113 large polyps (76.3 %) with a mean size of 25 +/- 4.7 mm (range 20 - 39 mm) and 35 giant polyps (23.7 %) with a mean size of 48.8 +/- 12.5 mm (range 40 - 100 mm). The most frequent location was the rectum, occurring in 43.2 %. All lesions were removed in a single session. En bloc resection was performed in 65 cases (43.9 %) and piecemeal in 83 (56.1 %). Procedural bleeding occurred in 13 EMRs (8.8 %), and one case of early and one case of delayed bleeding also occurred. There were two cases of postpolypectomy syndrome and one case of perforation. Malignancy (intramucosal and invasive cancer) was mostly present in polyps with sessile shape ( P = 0.0013). Follow-up colonoscopy was performed in 142 patients for a mean of 29.8 months. Recurrence was observed in 6/142 (4.2 %) patients and was found more in patients with giant polyps ( P = 0.014). CONCLUSIONS In our experience EMR is a simple and safe procedure for removing large and giant sessile and flat colorectal polyps, and is associated with a very low risk of complication and local recurrence.

Intraductal papillary or mucinous tumors (IPMT) of the pancreas: Report of a case series and review of the literature

OBJECTIVES:Despite a better understanding of these co intraductal papillary or mucinous tumors (IPMT) of the pancreas still present difficulty relating to the predictive factors of malignancy and the risk of relapse after surgical resection. The aim of this study was to report on our experience and to compare it to previously published cases.METHODS:We studied retrospectively 26 patients (mean age 60.3 yr) presenting with IPMT. Of the 26 patients, 19 had surgical resection and seven did not. The main clinical feature was acute pancreatitis occurring in 38% of the patients. Segmental pancreatectomy was performed in all the cases. At pathological assessment of resection margins, tumor resection was considered as complete in 17 cases. Margins exhibited benign mucinous involvement, and resection was considered to be incomplete in one multifocal case and in one case with diffuse spread of the tumor.RESULTS:A total of 11 tumors were benign and five were malignant. Carcinomas were invasive in four cases (two invading the pancreatic parenchyma, one the duodenum, and one the peripancreatic nodes) and in situ in one case. Malignancy was not diagnosed preoperatively except when invasion was evident (duodenal spread). Although main pancreatic duct type and obstructive jaundice appeared as suggestive features for the risk of malignancy, no reliable preoperative predictive factors for malignancy could be identified as regarding to clinical parameters, biological examinations, carcinoembryonic antigen or CA19-9 levels in serum or in pure pancreatic juice, imaging, and cytological methods. Within 40.8 months mean follow-up after surgery (range 2–96 months), three patients (16%), two with malignant and one with benign tumor, had tumor relapse after respectively 7, 27, and 14 months. Margins were positive without malignant features in the two malignant cases and negative in the other case. Tumor relapse was malignant with diffuse spreading in the three cases, and the patients died within 34 months after surgical resection.CONCLUSIONS:Our series and the review of the literature indicate that preoperative indicators of malignancy in IPMT are still lacking. Concerning resection margins, complete tumor resection is usually possible by segmental pancreatectomy. Malignant relapses are not exceptional. Incomplete resection and diffuse or multifocal tumor represent poor prognostic factors. Total pancreatectomy should be considered in such cases.

Depression, Anxiety and Anger in Subtypes of Irritable Bowel Syndrome Patients

The present study aimed to elucidate the differences in depression, anxiety, anger, and quality of life in a sample of non-psychiatric IBS patients, starting from the hypothesis that IBS subtypes may have different symptomatic expressions of negative emotions with different outcomes on quality of life measures. Forty-two constipation-predominant IBS (C-IBS) subjects and 44 diarrhea-predominant IBS (D-IBS) subjects, after an examination by a gastroenterologist and a total colonoscopy, underwent a clinical interview and psychometric examination for the assessment of depression, anxiety, anger and quality of life. IBS subtypes showed different symptomatic profiles in depression, anxiety and anger, with C-IBS patients more psychologically distressed than D-IBS subjects. Affective and emotional symptoms should be considered as specific and integral to the syndrome, and recognizing the differences between IBS subtypes may have relevant implications for treatment options and clinical outcome.

Optical coherence tomography evaluation of ulcerative colitis: the patterns and the comparison with histology.

HYPOTHESIS:The optical coherence tomography (OCT) is an imaging modality based on infrared light backscattering properties of tissues. OCT studies documented the disappearance of crypts and the alteration in light backscattering as features of ulcerative colitis (UC) in human colon. This technique should be more and more able to identify tissue microstructures with a resolution that is nearly that of histology (optical biopsy).AIM:To evaluate whether there are OCT patterns specific for UC and to compare the overall technique performance with the histology.METHODS:A total of 27 patients (20–76 yr) with UC underwent OCT imaging during a total colonoscopy. The OCT images were collected both from affected and normal sites in active UC or disease in remission. Two biopsies of the same sites were acquired. The OCT images were separately scored. Two pathologists blinded to the endoscopic and OCT patterns scored the samples.RESULTS:Three OCT patterns were identified: the mucosal backscattering alteration (MBA), the delimited dark areas (DDA), and the layered colonic wall (LCW). In colon affected segments of active and UC in remission, these patterns showed a good correspondence with the histology. Moreover, in 14/25 (56%) normal sites above the affected segment, the OCT documented the pathological features, confirmed only in 10/14 by the histology. Thus, the assessed sensitivity and specificity of OCT in normal segments of UC patients have been 100% and 69%, respectively.CONCLUSIONS:The in vivo OCT correctly detected disease features in endoscopically affected colon segments, but even in apparently normal segments of UC patients.

Ischemic Colitis Following Colonoscopy in a Systemic Lupus Erythematosus Patient: Report of a Case

BACKGROUNDIschemic colitis is an uncommon complication in patients with systemic lupus erythematosus but may be precipitated by colonoscopy.CASE REPORTA 43-year-old female with systemic lupus erythematosus under treatment with immunosuppressive drugs and prednisone was submitted to colonoscopy because of a change in bowel habit. Apart from the presence of a small metaplastic polyp, colonoscopy showed only a few erythematosus areas in the sigma and left colon. Four hours after colonoscopy, the patient developed lower colic abdominal pain and mucous diarrhea followed by rectal bleeding from ischemic colitis. The patient was successfully treated with fluids, spasmolytic drugs, sodic heparin, antibiotics and enteral feeding.CONCLUSIONSAwareness of the risk of this potential complication, secondary to colonoscopy, in patients with connective tissue disorders may lead to a prompt diagnosis and effective treatment, with a successful outcome.

An endoscopic approach to the management of surgical bile duct injuries: nine years’ experience

BACKGROUND The evaluation of the endoscopic treatment of surgical bile duct injuries, especially in the management of post-operative strictures, remains controversial. AIM The aim of this study was to evaluate the feasibility of using endoscopic management from a study of the clinical reports of two of the main endoscopy units in Sicily. PATIENTS AND METHODS A total of 137 consecutive patients were selected. There were 85 simple biliary fistulas: 64 from the cystic duct stump; 19 from the gall bladder bed; and two from intra-hepatic bile ducts. There were 52 biliary lesions: 15 complete transections; 12 incomplete lesions of the common bile duct with six associated strictures; five complete or incomplete sections of the right antero-medial duct; and 20 incomplete strictures (without leak). RESULTS The success rate was 96.3% for simple biliary fistulas. Endoscopic therapy was feasible only in 40.6% of lesions of the common bile duct or the right antero-medial duct (13/32), but with 100% success. In the case of strictures (with or without associated leak), there was a good outcome in 88.2% of patients who completed the therapeutic procedure. CONCLUSIONS Endoscopic management of simple biliary fistulas and incomplete lesions of the common bile duct is the preferred approach. If continued for 12-24 months, with the placement of three or more 10F stents, the management of stenoses is guaranteed to yield good results.

Appropriateness guidelines and predictive rules to select patients for upper endoscopy: A nationwide multicenter study

OBJECTIVES:Selecting patients appropriately for upper endoscopy (EGD) is crucial for efficient use of endoscopy. The objective of this study was to compare different clinical strategies and statistical methods to select patients for EGD, namely appropriateness guidelines, age and/or alarm features, and multivariate and artificial neural network (ANN) models.METHODS:A nationwide, multicenter, prospective study was undertaken in which consecutive patients referred for EGD during a 1-month period were enrolled. Before EGD, the endoscopist assessed referral appropriateness according to the American Society for Gastrointestinal Endoscopy (ASGE) guidelines, also collecting clinical and demographic variables. Outcomes of the study were detection of relevant findings and new diagnosis of malignancy at EGD. The accuracy of the following clinical strategies and predictive rules was compared: (i) ASGE appropriateness guidelines (indicated vs. not indicated), (ii) simplified rule (≥45 years or alarm features vs. <45 years without alarm features), (iii) logistic regression model, and (iv) ANN models.RESULTS:A total of 8,252 patients were enrolled in 57 centers. Overall, 3,803 (46%) relevant findings and 132 (1.6%) new malignancies were detected. Sensitivity, specificity, and area under the receiver-operating characteristic curve (AUC) of the simplified rule were similar to that of the ASGE guidelines for both relevant findings (82%/26%/0.55 vs. 88%/27%/0.52) and cancer (97%/22%/0.58 vs. 98%/20%/0.58). Both logistic regression and ANN models seemed to be substantially more accurate in predicting new cases of malignancy, with an AUC of 0.82 and 0.87, respectively.CONCLUSIONS:A simple predictive rule based on age and alarm features is similarly effective to the more complex ASGE guidelines in selecting patients for EGD. Regression and ANN models may be useful in identifying a relatively small subgroup of patients at higher risk of cancer.

Optical coherence tomography in inflammatory bowel disease: prospective evaluation of 35 patients.

PurposeOptical coherence tomography is a technique using infrared light in tissues of the gastrointestinal tract and human colon affected by inflammatory diseases. We evaluated whether there are specific patterns of optical coherence tomography for inflammatory bowel disease and compared the technique performance to the histology.MethodsOptical coherence tomography was performed in 35 patients (18 men; 31 ulcerative colitis, 4 Crohn’s disease). The images were obtained from affected and normal colon at endoscopy. Two biopsies of the sites visualized were taken. Two endoscopists scored the images, and two pathologists, blind to the endoscopy and optical coherence tomography, performed the histologic evaluation.ResultsThree optical coherence tomography patterns were identified: 1) mucosal backscattering alteration, 2) delimited dark areas, and 3) layered colonic wall. Compared with the histology, mucosal backscattering alteration was the most effective in recognizing the disease in patients (P = 0.007 in colon segments affected, and P < 0.001 in normal segments). The sensitivity and specificity have been 100 and 78 percent, respectively.ConclusionsThe in vivo optical coherence tomography correctly detected inflammatory bowel disease features in affected and apparently normal colon, and allowed to discriminate patterns for active ulcerative colitis and Crohn’s disease.