Enzo Masci

Gabexate for the Prevention of Pancreatic Damage Related to Endoscopic Retrograde Cholangiopancreatography

BACKGROUND Endoscopic retrograde cholangiopancreatography (ERCP) is associated with elevated levels of pancreatic enzymes and pancreatitis. Gabexate, a protease inhibitor, has been used to prevent pancreatic damage related to ERCP. METHODS We conducted a multicenter, double-blind comparison of gabexate (1 g given by intravenous infusion starting 30 to 90 minutes before endoscopy and continuing for 12 hours afterward) with placebo (mannitol and sodium chloride, administered in the same fashion). A total of 435 adults scheduled to undergo ERCP and, when indicated, endoscopic sphincterotomy underwent randomization; 17 were excluded from the final analysis for various reasons. The remaining 418 patients (mean age, 60.4 years)--208 in the gabexate group and 210 in the placebo group--were analyzed. Acute pancreatitis was considered to be present if serum amylase or lipase levels (or both) were five times greater than the upper limits of normal in association with the onset of pancreatic pain. RESULTS After the procedures, 276 patients (66 percent) had elevated pancreatic-enzyme levels; the frequency was similar in the two groups. Mean serum amylase values were higher in the placebo group than in the gabexate group through 24 hours of observation (P=0.03). Twelve patients in the gabexate group and 29 in the placebo group had abdominal pain (6 percent vs. 14 percent, P=0.009). Sixteen patients in the placebo group and five in the gabexate group had acute pancreatitis (8 percent vs. 2 percent, P=0.03). Two patients treated with gabexate and six given placebo had adverse events, all of which resolved. Two patients given placebo died of acute pancreatitis; one was excluded from the evaluation because pancreatitis was present before endoscopy. One patient in the gabexate group died, from a myocardial infarction. CONCLUSION Prophylactic treatment with gabexate reduced pancreatic damage related to ERCP, as reflected by reductions in the extent but not the frequency of elevated enzyme levels and in the frequency of pancreatic pain and acute pancreatitis.

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.

Secretin MRCP and endoscopic pancreatic manometry in the evaluation of sphincter of Oddi function: a comparative pilot study in patients with idiopathic recurrent pancreatitis

BACKGROUND Sphincter of Oddi dysfunction plays an important etiologic role in idiopathic acute recurrent pancreatitis. Sphincter of Oddi manometry is the most accurate test of sphincter of Oddi function, but it is associated with an increased risk of post-procedure pancreatitis and is non-diagnostic in about a third of cases. Secretin MRCP has a diagnostic efficacy comparable to ERCP, but data on its sensitivity with regard to sphincter of Oddi function are lacking. The aim of this study was to compare secretin MRCP and pancreatic sphincter of Oddi manometry for evaluation of sphincter of Oddi function in patients with idiopathic acute recurrent pancreatitis. METHODS Eighteen consecutive patients with idiopathic acute recurrent pancreatitis underwent secretin MRCP and pancreatic sphincter of Oddi manometry/ERCP. Data from 15 patients were suitable for analysis. Fifteen subjects with asymptomatic, non-pancreatic hyperamylasemia matched for age and gender underwent secretin MRCP and served as a control group. RESULTS Sphincter of Oddi manometry documented sphincter dysfunction in 6/15 patients (40%) and secretin MRCP, in 4/15 patients (26.7%). Sphincter of Oddi manometry confirmed the presence of elevated basal sphincter of Oddi pressure in two of the 4 patients with abnormal and other forms of sphincter of Oddi dyskinesia in the other two. None of the control subjects had an abnormal secretin MRCP. Secretin MRCP and sphincter of Oddi manometry were concordant in 13/15 patients (86.7%); positive and negative diagnoses for sphincter of Oddi dysfunction agreed in, respectively, 81.8% and 100% (kappa value 0.706). CONCLUSIONS Secretin MRCP seems to be a useful noninvasive procedure for investigation of pancreatic sphincter of Oddi function, but evaluation in larger series is needed.

Endoscopic palliation in patients with incurable malignant colorectal obstruction by means of self-expanding metal stent: Analysis of results and predictors of outcomes in a large multicenter series

OBJECTIVES To evaluate the short- and long-term efficacy of self-expanding metal stents (SEMSs) in patients with colorectal obstruction and incurable cancer and the related factors that affect outcomes. DESIGN Retrospective analysis of SEMS placement for incurable colorectal obstruction in a 3-year period. SETTING Five tertiary care endoscopic centers. PATIENTS AND INTERVENTION Consecutive patients (N = 201) undergoing stenting for incurable malignant obstruction. MAIN OUTCOME MEASUREMENTS Clinical and technical success of stenting, complications rate, and factors affecting outcomes. RESULTS Technical success was achieved in 184 of 201 patients (91.5%) and clinical success occurred in 165 of 184 patients (89.7%; 82.1% of 201 patients). Technical and clinical failures were more frequent in extrinsic and long colorectal stenoses. Overall, 165 patients had normal bowel movements during follow-up (mean [SD], 115.5 [100.3] days; range, 1-500 days), 15 developed complications, 127 had a functioning SEMS at the time of death, and 23 were alive at completion of the study. Twenty-four (11.9%) major complications occurred: 11 migrations, 12 perforations, and 1 reobstruction. Migration of SEMSs was associated with stent diameter less than 25 mm. Bevacizumab therapy increased the risk of perforation by 19.6-fold. Karnofsky performance status of 50 or less was associated with shorter survival and a 3.7-fold higher risk of death within 6 months after the stent was placed. CONCLUSIONS The use of SEMSs is safe and effective for palliation of incurable malignant colonic obstruction; approximately 75% of patients with SEMSs are able to avoid colostomy.

Comparison of two dosing regimens of gabexate in the prophylaxis of post-ERCP pancreatitis

OBJECTIVES:A continuous 13-h infusion of gabexate starting 30–90 min before endoscopic cholangiopancreatography (ERCP) can reduce postprocedural pancreatitis, the onset of which is generally observed within the first 6 h after ERCP. This study was designed to verify whether a 6.5-h infusion of gabexate was as effective as a 13-h infusion, at the same concentration, for reducing the incidence of post-ERCP pancreatitis (primary endpoint) and pancreatic hyperenzymemia and pain (secondary endpoints).METHODS:A total of 434 patients (201 male and 233 female; mean age 63.9 yr, range 18–96 yr) scheduled for ERCP were prospectively recruited in 25 Italian centers. Patients were randomized double-blind to two treatment groups. All subjects enrolled were first treated with a 500-mg continuous intravenous infusion of gabexate, starting 30 min before the endoscopic maneuvers and continuing up to 6.5 h after it. Over the next 6.5 h, 214 patients (group I) continued the infusion of gabexate (for a total of 1 g over 13 h) and 220 patients (group II) were given placebo (saline solution).RESULTS:The overall incidence of acute pancreatitis was 1.8% (eight patients), which included 1.4% in group I (three of 214 patients) and 2.2% in group II (five of 220 patients). Serum amylase and lipase values over time, peak levels of the two enzymes, pancreatic pain, and need for analgesics did not significantly differ in the two groups.CONCLUSIONS:These results suggest that a 6.5-h infusion of gabexate (for a total of 500 mg) is not less effective than a 13 h infusion, with evident savings.

Endoscopic closure of acute iatrogenic perforations during diagnostic and therapeutic endoscopy in the gastrointestinal tract using metallic clips: A literature review

Iatrogenic perforations that occur during the endoscopic procedures are generally surgically managed, even if some authors prefer a non‐surgical approach in selected cases. The endoscopic application of metallic clips has been widely used in the gastrointestinal (GI) tract for hemostasis and also for marking lesions. Since 1993 several series of endoscopic perforations treated with endoclips have been described in the literature. In this review we offer a descriptive analysis of the reported cases of the acute iatrogenic perforation, describing the closure of different perforations occurring in the GI tract, treated with metallic clips.

Fully covered self-expandable metallic stents in benign biliary strictures: a multicenter study on efficacy and safety

BACKGROUND AND STUDY AIM Benign biliary diseases include benign biliary stricture (BBS), lithiasis, and leaks. BBSs are usually treated with plastic stent placement; use of uncovered or partially covered metallic stents has been associated with failure related to mucosal hyperplasia. Some recently published series suggest the efficacy of fully covered self-expandable metal stents (FCSEMSs) in BBS treatment. We aimed to assess the efficacy and safety of FCSEMS in a large series of patients with BBS and a long follow-up.  PATIENTS AND METHODS Prospective multicenter clinical study at three tertiary referral centers: ISMETT/UPMC Italy, Palermo, San Paolo Hospital, Milan, and the ARNAS Civico Hospital, Palermo, Italy. All consecutive patients with BBS were treated with placement of FCSEMS rather than plastic stents, as first approach (11 patients, 17.7 %), or as a second approach after failure of other treatments (51 patients, 82.2 %). RESULTS From January 2008 to March 2011, 62 patients (40 male) were included. Mean period of FCSEMS indwelling was 96.7 days (standard deviation [SD] 6.5 days). In 15 patients (24.2 %) the SEMS migrated. Resolution of BBS occurred in 56 patients (90.3 %), while in 6 (9.6 %) the treatment failed. Mean (SD) follow-up after SEMS removal was 15.9 (10) months. FCSEMS placement as first- or second-line approach showed no difference in failure. Recurrence was observed in 4 /56 patients (7.1 %); all were transplant recipients: P = 0.01; odds ratio (OR) 1.2, confidence interval (CI) 1.1 - 1.3. CONCLUSIONS Despite the noteworthy migration rate, FCSEMSs should be considered effective for refractory benign biliary strictures. Further studies are needed to assess their role as a first approach in the management of BBS.

Intraductal optical coherence tomography for investigating main pancreatic duct strictures

BACKGROUND AND STUDY AIMS:Optical coherence tomography (OCT) permits high-resolution imaging of tissue microstructures using a probe that can be inserted into the main pancreatic duct (MPD) through a standard endoscopic retrograde cholangiopancreatography (ERCP) catheter. This prospective study was designed to assess the diagnostic capacity of OCT to differentiate between nonneoplastic and neoplastic lesions in patients with MPD segmental strictures.PATIENTS AND METHODS:Twelve consecutive patients with documented MPD segmental stricture were investigated by endoscopic ultrasonography (EUS), with fine-needle aspiration cytology if necessary, and ERCP, followed by brush cytology and OCT scanning.RESULTS:OCT recognized a differentiated three-layer architecture in all cases with normal MPD or chronic pancreatitis, while in all the neoplastic lesions the layer architecture appeared totally subverted, with heterogeneous backscattering of the signal. The accuracy of OCT for detection of neoplastic tissue was 100% compared with 66.7% for brush cytology. In one case, neither OCT scanning nor brush cytology was possible because of the severity of the stricture.CONCLUSIONS:This pilot study showed that OCT is feasible during ERCP, in cases of MPD segmental stricture, and was superior to brush cytology in distinguishing nonneoplastic from neoplastic lesions.

Hemospray Application in Nonvariceal Upper Gastrointestinal Bleeding: Results of the Survey to Evaluate the Application of Hemospray in the Luminal Tract.

Background: Hemospray TM (TC-325) is a novel hemostatic agent licensed for use in nonvariceal upper gastrointestinal bleeding (NVUGIB) in Europe. Goals: We present the operating characteristics and performance of TC-325 in the largest registry to date of patients presenting with NVUGIB in everyday clinical practice. Methods: Prospective anonymized data of device performance and clinical outcomes were collected from 10 European centers using the multicentre SEAL survey (Survey to Evaluate the Application of Hemospray in the Luminal tract). TC-325 was used as a monotherapy or as second-line therapy in combination with other hemostatic modalities at the endoscopists’ discretion. Results: Sixty-three patients (44 men, 19 women), median age 69 (range, 21 to 98) years with NVUGIB requiring endoscopic hemostasis were treated with TC-325. There were 30 patients with bleeding ulcers and 33 with other NVUGIB pathology. Fifty-five (87%) were treated with TC-325 as monotherapy; 47 [85%; 95% confidence interval (CI), 76%-94%] of them achieved primary hemostasis, and rebleeding rate at 7 days was 15% (95% CI, 5%-25%). Primary hemostasis rate for TC-325 in patients with ulcer bleeds was 76% (95% CI, 59%-93%). Eight patients, who otherwise may have required either surgery or interventional radiology, were treated with TC-325 as second-line therapy after failure of other endoscopic treatments, all of whom achieved hemostasis following the adjunct of TC-325. Conclusions: This multicentre registry identifies potentially useful characteristics of Hemospray (TC-325) when used either as monotherapy or as a rescue therapy in a wide variety of ulcer and nonulcer NVUGIB.

Second-line levofloxacin-based triple schemes for Helicobacter pylori eradication

BACKGROUND The recommended second-line therapy for Helicobacter pylori (H. pylori) eradication is a quadruple regimen that fails in up to 30% of patients. Several recent studies suggest levofloxacin-based triple therapies as an alternative rescue treatment. However, dosage and length of levofloxacin-based regimens have not been established. AIM To compare the efficacy and tolerability of four second-line levofloxacin-based schemes for H. pylori eradication. METHODS One hundred and sixty patients (aged 18-70 years, 72 male patients) who were H. pylori positive after standard triple therapies were randomised to receive esomeprazole 20mg b.d. and amoxicillin 1g b.d. plus levofloxacin 500 mg o.d., for 7 or 10 days (Groups A and B) or levofloxacin 500 mg b.d. for 7 days or 10 days (Groups C and D). H. pylori status was assessed by 13-C Urea Breath Test or rapid urease test, before and 6 weeks after therapy. Incidence of side effects was evaluated by a questionnaire. RESULTS No dropouts were observed. Eradication of H. pylori infection was successful in: 65% of patients in Group A; 90% in Group B; 70% in Group C; 85% in Group D. Based upon duration of treatment, eradication rates were: 67.5% in 7 days groups and 87.5% in 10 days groups (p=0.004). Dosage of levofloxacin did not affect the eradication rates (77.5% both in the once daily and twice daily groups). Mild adverse events were reported overall in 16% of patients (22.5% in 7 days groups; 27.5% in 10 days groups; p=0.58; 12% in the once daily group; 32.5% in the twice daily group; p=0.04). CONCLUSIONS 10 days levofloxacin-based second-line regimens were effective in curing H. pylori infection in more than 85% of patients with a lower incidence of adverse effects in levofloxacin single-dosage scheme. The 10 days levofloxacin-based regimens were more effective than 7 days course of treatment showing that duration of therapy is the crucial factor affecting eradication rate.