First-line therapies for H. pylori infection in Italy: a pooled-data analysis.

Background: Curing H. pylori infection remains challenging, and the use of most effective first-line therapy represents a therapeutic cornerstone. To monitor the efficacy of first-line therapies in Italy, we designed a systematic review with pooled- data analysis of data published in the last 15 years. Methods: The search was focused on standard regimens and adult patients. Studies that included modified therapy regimens, pediatric patients, case series with less than 5 patients, and those in language other than English were excluded. Results: A total of 40 studies, with 74 therapeutic arms and 13,539 patients were evaluated. Among the 14-day triple therapies, the combination with proton pump inhibitor (PPI), clarithromycin and amoxicillin achieved the highest (77.9%) success rate, whilst the lowest success rate (62.7%) was observed following the 14-day PPI, clarithromycin and tinidazole regimen. The overall efficacy of triple therapies significantly decreased from 75.7% to 72.1% in the last decade. Sequential (88.3% on 3431 patients), concomitant (88.8% on 376 patients), and the bismuth-based quadruple therapy with three-in-one capsule, containing bismuth subcitrate potassium (140 mg), metronidazole (125 mg), tetracycline (125 mg) (90.4% on 999 patients) achieved similarly high eradication rates, but data on concomitant are still limited. The bismuth-based was associated with the higher (38.7%) incidence of side-effects. Conclusions: Data found that all triple therapies, irrespective of drug combination and therapy duration, should be abandoned in Italy due to their unacceptable low success rates. Monitoring the efficacy of standard first-line therapies in other countries could be clinically useful for both patients and clinicians.

Optimal processing of ESD specimens to avoid pathological artifacts.

BACKGROUND: En bloc endoscopic submucosal dissection (ESD) has been recently introduced as a treatment for precancerous/neoplastic gastrointestinal conditions. The aim of the present study was histological assessment of en bloc ESD specimens. METHODS: Fifty-three ESD specimens were positioned over a cellulose acetate support (40 specimens; 12 from the upper gastrointestinal tract and 28 from the lower gastrointestinal tract) or pinned with nails on polystyrene or cork (13 specimens; 7 from the upper gastrointestinal tract and 6 from the lower gastrointestinal tract). We cut consecutive 2 mm-thick sections stained with hematoxylin and eosin. From the first and the last sections, we obtained a second slide, after a 180° rotation and re-embedding. The quality of ESD samples was scored as inadequate, suboptimal and adequate, based on the amount of crushing, shearing and stretching artifacts that were scored from 0 (absent) to 2 (diffuse or maximum). From the sum of these we obtained a global artifact score (GAS). RESULTS: Removed lesions were: adenocarcinoma (5 cases), neuroendocrine tumor (NET) G1 (1 case), premalignant conditions, including adenomatous polyps (41 cases) and hyperplastic lesions (6 cases). A positive deep surgical margin was found in 8/53 cases (15%): high- and low-grade dysplastic glands were detected in 5 cases, low-grade adenocarcinoma in 2, and NET cells in 1. Dysplastic glands were detected in the lateral surgical margins of 12 ESD specimens (23%). Among the ESD specimens positioned on the cellulose acetate support, apart from the modifications due to electrocoagulation, 2 (5%) showed shearing modifications. In the group of ESD specimens fixed with nails, 5 (38%) showed shearing, 10 (77%) crushing artifacts, 11 (85%) stretching and 11 (85%) multiple holes caused by the nails. On the basis of these data all histological specimens from ESD on cellulose acetate were adequate (GAS 0-1).However, in the group of ESD fixed with nails, 1 was adequate (GAS 0), 11 suboptimal (GAS 2-5) and 1 inadequate (GAS 6). CONCLUSIONS: Specific devices including cellulose support and adequate sampling blocks can be helpful to perform accurate histological assessment of ESD specimens after en bloc ESD for precancerous/neoplastic gastrointestinal lesions, with complete analysis of the status of the margins and the entirely en bloc evaluation of the lesion.

Cameron lesions: A still overlooked diagnosis. Case report and systematic review of literature.

Cameron lesions are erosive-ulcerative alterations of gastric mucosa occurring in patients with large hiatal hernia, potentially causing gastrointestinal bleeding and iron deficiency anaemia. Diagnosis may be challenging, and not infrequently erosions are overlooked at endoscopy, so that repeated and unnecessary diagnostic procedures are performed, particularly in those patients with chronic anaemia. We described two peculiar cases of patients with iron deficiency anaemia in whom Cameron lesions were either overlooked or misinterpreted. By reviewing data of 22publications reporting endoscopic and clinical data of 140patients, we noted a large prevalence of females (75%). The most frequent presenting symptoms were anaemia (62%) and overt gastrointestinal bleeding (36%). Noteworthy, as many as 69% of patients underwent one or more previous upper endoscopy before diagnosis of Cameron lesion was achieved. Patients were mainly treated with proton pump inhibitor (PPI) therapy and iron supplementation. Moreover, endoscopic haemostasis was performed in 10% of case, blood transfusion was required in one third of cases, and a similar quote of patients underwent a surgical approach for hiatal hernia repair. The observation that as many as 60% patients were already receiving standard PPI therapy when diagnosis was performed would suggest that either long-term treatment with adequate dose PPI or surgical approach for hiatal hernia repair is required. In conclusion, Cameron lesion is still an overlooked diagnosis in patients with iron deficiency anaemia in whom a 5-9.2% prevalence has been reported.

Complications during colonoscopy: prevention, diagnosis, and management.

Colonoscopy is largely performed in daily clinical practice for both diagnostic and therapeutic purposes. Although infrequent, different complications may occur during the examination, mostly related to the operative procedures. These complications range from asymptomatic and self-limiting to serious, requiring a prompt medical, endoscopic or surgical intervention. In this review, the complications that may occur during colonoscopy are discussed, with a particular focus on prevention, diagnosis, and therapeutic approaches.

Non-steroidal anti-inflammatory drug - induced transient reactive papulotranslucent acrokeratoderma.

Transient reactive papulotranslucent acrokeratoderma (TRPA) is an unusual skin condition characterized by the rapid and transient development of symmetric, edematous white papules with eccrine duct prominence on the palms after exposure to water. We present the case of a 28-year-old woman diagnosed in our clinic with TRPA induced by the use of a non-steroidal anti-inflammatory drug. The possible pathophysiology and treatment options are discussed.

Prevalence and risk factors of extrapancreatic malignancies in a large cohort of patients with intraductal papillary mucinous neoplasm (IPMN) of the pancreas.

BACKGROUND: The objectives of this study are to estimate prevalence and incidence of extrapancreatic malignancies (EPMs) among intraductal papillary mucinous neoplasms (IPMNs) of the pancreas, and to identify risk factors for their occurrence. PATIENTS AND METHODS: We conducted multicentric cohort study in Italy from January 2010 to January 2011 including 390 IPMN cases. EPMs were grouped as previous, synchronous (both prevalent) and metachronous (incident). We calculated the observed/expected (O/E) ratio of prevalent EPMs, and compared the distribution of demographic, medical history and lifestyle habits. RESULTS: Ninety-seven EPMs were diagnosed in 92 patients (23.6%), among them 78 (80.4%) were previous, 14 (14.4%) were synchronous and 5 (5.2%) were metachronous. O/E ratios for prevalent EPMs were significantly increased for colorectal carcinoma (2.26; CI 95% 1.17-3.96), renal cell carcinoma (6.00; CI 95% 2.74-11.39) and thyroid carcinoma (5.56; CI 95% 1.80-12.96). Increased age, heavy cigarette smoking, alcohol consumption and first-degree family history of gastric cancer are significant risk factors for EPMs, while first-degree family history of colorectal carcinoma was borderline. CONCLUSION: We report an increased prevalence of EPMs in Italian patients with IPMN, especially for colorectal carcinoma, renal cell and thyroid cancers. A systematic surveillance of IPMN cases for such cancer types would be advised.

Esophageal chemical clearance is impaired in gastro-esophageal reflux disease--a 24-h impedance-pH monitoring assessment.

BACKGROUND: Impedance-pH monitoring allows assessment of retrograde and antegrade intra-esophageal movement of fluids and gas. Reflux is followed by volume clearance and chemical clearance, elicited by secondary and swallow-induced peristalsis, respectively. We aimed to assess whether chemical clearance is impaired in gastro-esophageal reflux disease (GERD). METHODS: Blinded retrospective review of impedance-pH tracings from patients with erosive reflux disease (ERD) and non-erosive reflux disease (NERD), and from proton pump inhibitor (PPI)-refractory patients before and after laparoscopic fundoplication. The number of refluxes followed within 30 s by swallow-induced peristaltic waves was divided by the number of total refluxes to obtain a parameter representing chemical clearance namely the postreflux swallow-induced peristaltic wave (PSPW) index. KEY RESULTS: The PSPW index was significantly lower in 31 ERD (15%) and in 44 NERD (33%) off-PPI patients than in 30 controls (75%), as well as in 18 ERD (16%) and in 48 NERD (31%) on-PPI patients than in 26 on-PPI functional heartburn (FH) cases (67%) (P < 0.05 for all comparisons). In 29 PPI-refractory patients, the median PSPW index was unaltered by otherwise effective antireflux surgery (20% postoperatively, 21% preoperatively). The overall sensitivity, specificity, positive, and negative predictive values of the PSPW index in identifying GERD patients were 97%, 89%, 96%, and 93%. CONCLUSIONS & INFERENCES: Impairment of chemical clearance is a primary pathophysiological mechanism specific to GERD: it is unaffected by medical/surgical therapy, is not found in FH, and is more pronounced in ERD than in NERD. Using the PSPW index could improve the diagnostic efficacy of impedance-pH monitoring.

Reflux parameters as modified by EsophyX or laparoscopic fundoplication in refractory GERD.

BACKGROUND: EsophyX is a novel transoral incisionless fundoplication device developed to mimic surgical fundoplication. EsophyX fundoplication improves acid reflux parameters in proton pump inhibitor (PPI)-responsive GERD patients but its efficacy in refractory GERD has been scarcely studied. AIM: To assess reflux parameters before and after EsophyX or laparoscopic fundoplication and their relationship with symptoms in refractory GERD. METHODS: In an open-label study, we enrolled prospectively patients with heartburn/regurgitation persisting despite high-dose PPI therapy. Impedance-pH monitoring was performed on PPI therapy before intervention and off PPI therapy 3 months after intervention. RESULTS: Ten patients chose to undergo EsophyX (EndoGastric Solutions, Redmond, WA, USA) fundoplication while ten chose laparoscopic fundoplication, and the baseline characteristics were comparable. Distal and proximal refluxes were significantly reduced post-operatively in the surgical but not in the endoscopic group and the median values were significantly lower in the former than in the latter. The oesophageal acid exposure time was normal in 50% of cases after EsophyX and in 100% of cases after surgery (P=0.033); the number of distal refluxes was normal in 20% and 90% of cases (P=0.005) and the number of proximal refluxes was normal in 40% and 100% of cases (P=0.011), respectively. A positive persisting symptom-reflux association was found post-operatively in 6/10 patients in the EsophyX group and in 0/10 patients in the surgical group (P=0.011). CONCLUSIONS: In patients with refractory GERD, EsophyX fundoplication is significantly less effective than laparoscopic fundoplication in improving reflux parameters and accordingly, in inducing symptom remission.

Endoscopic treatment of gastrointestinal fistulas using an over-the-scope clip (OTSC) device: case series from a tertiary referral center.

Gastrointestinal perforations and post-surgical fistulas are dreaded complications that dramatically increase morbidity and mortality. A new endoscopic over-the-scope clip (OTSC) system may be potentially useful for sealing visceral perforations in several clinical settings. We evaluated the advantages and clinical impact of the placement of OTSCs on the management of non-malignant gut leaks in 12 consecutive patients. OTSCs of 9.5 or 10.5 mm were used, according to the diameter of the defect within the wall. The indications for treatment were mainly related to post-surgical fistulas. Healing of the fistula was assessed by endoscopic or radiological means, and failed only once. No OTSC-related complications occurred. Endoscopic closure of perforations and post-surgical fistulas with the OTSC system is a simple and minimally invasive technique. This approach, when feasible, may be less expensive and more advantageous than a surgical approach.

Reflux patterns in patients with short-segment Barrett's oesophagus: a study using impedance-pH monitoring off and on proton pump inhibitor therapy.

BACKGROUND: In short-segment Barrett's oesophagus (SSBO) heartburn may be absent and oesophageal acid exposure time (OAET) assessed with pH-only monitoring may be normal. By detecting reflux episodes independently of their acidity, multichannel intraluminal impedance-pH (MII-pH) monitoring allows a comprehensive characterization of reflux events, either off or on proton pump inhibitor (PPI) therapy. AIM: To assess reflux parameters by MII-pH monitoring in newly diagnosed SSBO, at baseline and as modified with PPI therapy. METHODS: Short-segment Barrett's oesophagus was defined by oesophageal intestinal metaplasia up to 3 cm in length. 24-h MII-pH monitoring was performed before and during PPI therapy. RESULTS: Fifty patients were studied prospectively. Normal OAET was found at baseline in 15 patients (30%), 8 and 2 of whom with a higher than normal number of acid and weakly acidic refluxes, respectively. Overall, abnormal reflux parameters were detected by MII-pH monitoring in 90% of patients. Reflux events were prevalent in the upright period. On PPI therapy, acid refluxes decreased and a correspondent increase in weakly acidic refluxes was observed (median from 48.5 to 9 and from 16 to 57.5, respectively) (P < 0.001). CONCLUSIONS: Acid refluxes, mainly in the upright period, characterize SSBO. PPI therapy transforms acid refluxes into weakly acidic refluxes.

The influence of endoscopic biliary stents on the accuracy of endoscopic ultrasound for pancreatic head cancer staging.

BACKGROUND AND STUDY AIMS: Biliary stents have been found to interfere with endoscopic ultrasound (EUS) tumor (T) and nodal (N) staging in patients with periampullary cancer. Our aim was to determine whether this also occurs in patients with pancreatic head cancer. PATIENTS AND METHODS: We studied a consecutive series of patients who were undergoing preoperative EUS for diagnosis and staging of suspected pancreatic cancer, some of whom had biliary stents in situ and some of whom did not. The main end point was the uni- and multivariate association of biliary stenting with T and N mis-staging by EUS. The surgical T and N stages were used as gold standards. RESULTS: A total of 65 patients were identified (19 with biliary stents in situ and 46 without). Surgical stage T4 was found more frequently in patients with stents (53% vs. 22%, P = 0.014). The T stage by EUS was correct in 85% of the patients without biliary stents and in 47% of the patients with stents. The frequency of mis-staging by EUS was significant only among patients with a biliary stent. The distribution by EUS N stage did not differ significantly from the surgical N-stage distribution in the two groups of patients. According to the multivariate analysis, patients with stents were 6.55 times more likely to be incorrectly T staged (95% confidence interval [CI] 1.69-25.49) and 3.71 times more likely to be incorrectly N staged (95% CI 1.11-12.45) than patients without stents. CONCLUSIONS: The results add support to the recommendation that EUS staging of pancreatic head neoplasms should be performed prior to stent placement.

Acute gastric anisakiasis: an Italian experience.

Anisakidosis is a parasitic disease of the human gastrointestinal tract caused by ingestion of larvae of marine nematodes such as Anisakis spp. or, rarely, Pseudoterranova spp., present in raw or undercooked fish. We report the first series of gastric Anisakis infection (anisakiasis) from a single centre in Italy. In our department, we observed 3 cases, all in women who were urgently hospitalized following intense epigastric pain and vomiting, developed after the ingestion of raw fish. The patients underwent urgent gastroscopy within a few hours. In each, a worm was extracted from the gastric mucosa by means of biopsy forceps. This was followed by prompt clinical improvement. The worm was identified by its macroscopic and microscopic characteristics as an Anisakis spp. larva (L3). In 2 cases, laboratory tests revealed marked leukocytosis and eosinophilia in the peripheral blood 3-4 days after ingestion of the raw fish. The diagnosis of anisakiasis can be made by endoscopy, radiology and abdominal ultrasound, but is often made only at surgery. In the gastric form of the disease, urgent gastroscopy has both a diagnostic and a therapeutic role, because the worm can be removed by means of biopsy forceps.

Multicentre retrospective study on endoscopic ultrasound complications.

BACKGROUND: Endoscopic ultrasonography, both conventional and interventional, has been used increasingly during the past 20 years and is deemed a safe technique. Its complication rate, however, has been studied to only a limited extent. This multicentre investigation sought to establish the complication rate for a large number of endoscopic ultrasonography procedures. METHODS: By means of a questionnaire, we collected data from six centres on the number of endoscopic ultrasonography examinations performed and divided them into conventional and interventional examinations of the upper and lower gastrointestinal tract. Information was obtained on technical modalities such as instruments and sedation and, for interventional endoscopic ultrasonography, indications, pre-procedural exams and technical details (needle calibre, number of passes) had to be specified. Complications were classified as mild, moderate, severe or fatal and their onset as immediate, early or late. Variables that entered into the analysis of complication rate included type of endoscopic ultrasonography instrument used, type and site of lesion biopsied, number of needle passes and operator experience. RESULTS: Eleven thousand five hundred thirty nine endoscopic ultrasonographic procedures were reported, of which 10,731 were conventional and 808 interventional. No deaths occurred; there were 14 (0.12%) complications, 5 (0.046%) of them following conventional endoscopic ultrasonography and 9 (1.11%) after interventional endoscopic ultrasonography. Seven complications were mild, four moderate and three severe. CONCLUSIONS: Both conventional and interventional endoscopic ultrasonography were confirmed to be acceptably safe techniques.

Endoscopic treatment of postsurgical external pancreatic fistulas.

BACKGROUND AND STUDY AIMS: External pancreatic fistulas (EPFs) are managed primarily by conservative treatment with a success rate of 40-90%. Failures of conservative therapy have traditionally been dealt with using surgery; however, major morbidity and mortality are associated with operative treatment. The aim of this study was to evaluate the feasibility and effectiveness of endoscopic treatment in the closure of EPF. PATIENTS AND METHODS: A total of 16 consecutive patients with EPF (12 men, four women; median age 50, range 21-66) underwent an attempt at endoscopic management after failure of conservative therapy. Four patients had chronic pancreatitis. All patients had EPFs occurring after open abdominal surgery. The mean interval between the onset of the fistula and our intervention was 108 days (range 27-365 days). The mean output volume of the fistula was 205 ml/d (range 50-600 ml/ d). The aim of treatment was to lower the pancreatic duct pressure and to bypass the ductal disruption by placement of drains and/or stents to induce fistula healing. RESULTS: In all, 13 biliary and nine pancreatic sphincterotomies were performed in order to gain access to the pancreatic duct. Access through the minor papilla was required in one patient. Complete visualization of the main pancreatic duct as well as of the fistulous tract was obtained in 12 patients (75%). Treatment consisted of placement of a nasal pancreatic drain (NPD) across the pancreaticojejunal anastomosis in one patient after duodenopancreatectomy. In 11 of the remaining 15 patients (73%) a NPD could be placed in the pancreatic duct across the ductal leakage (n = 9) or nearby (n = 2). One patient died 24 hours after endoscopic treatment from severe sepsis and massive pulmonary embolism. Endoscopic drainage was effective in healing the EPF in all patients in whom NPDs had been successfully placed, except one. The fistula in this patient healed completely after insertion of an 8.5-Fr pancreatic stent. The mean interval between endoscopic treatment and fistula closure was 8.8 days (range 2-33 days). No complications related to the endoscopic treatment were recorded in this series. In the 12 successfully treated patients, fistulas did not recur in any of the 11 surviving patients after a mean follow-up of 24.7 months (range 3-63 months). CONCLUSIONS: Endoscopic pancreatic drainage, when feasible, is safe and effective for EPF and should be considered as a first-line therapy when EPFs do not respond to conservative therapy.