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Few studies have been published on the long-term outcomes of patients with gastric neuroendocrine tumors (gNETs). We analyzed their management over a two-decade period, focusing on endoscopic and clinical outcomes. Clinical, laboratory, endoscopic, surgical, and histopathological data from Types 1 and 3 gNETs histologically diagnosed between March 2000 and December 2021 at the European Institute of Oncology (IEO, Milan) were retrospectively collected. Sixty-nine patients were included (60 Type 1, 9 Type 3): 53 (77%) were treated endoscopically, 6 (9%) surgically, and 10 (14%) did not receive any treatment. Overall, 293 lesions were removed endoscopically: 74% by forceps, 20% by endoscopic mucosal resection (EMR), and 5% by endoscopic submucosal dissection (ESD). No differences were observed between EMR and ESD in terms of complete resection rate (p value = .50) and complications rate (p value = .084). The median follow-up period was 5.8 years (range: 0.3-20.5), during which no gNET-related deaths were observed. Metachronous gNETs developed in 60% of patients with Type 1 gNET. Six patients with lymph node metastases (LNM) were younger (p value = .006) and had larger lesions (p value <.001) than patients without LNM. Most Type 1 gNETs were successfully excised using forceps, with EMR and ESD being equally effective. The presence of incomplete resection was not associated with a worse prognosis, which remains excellent in this highly recurrent disease. Younger age and a size ≥10 mm were associated with an increased risk of LNM. CLINICAL TRIAL REGISTRATION: Project code UID 2854., (© 2024 British Society for Neuroendocrinology.)

Background: Successful bowel preparation (BP) for colonoscopy depends on the instructions, diet, the laxative product, and patient adherence, which all affect colonoscopy quality. Nevertheless, there are no laxatives which combine effectiveness, safety, easy self-administration, good patient acceptance, and low cost. However, mannitol, a sugar alcohol, could be an attractive candidate for use in clinical practice if it is shown to demonstrate adequate efficacy and safety., Aims: The present phase II dose-finding study compared three doses of mannitol (50, 100, and 150 g) to identify the best dose to be used in a subsequent phase III study., Methods: The Boston Bowel Preparation Scale, caecal intubation rate, adherence, acceptability, and safety profile, including measurement of potentially dangerous colonic gas concentrations (CH 4 , H 2 , O 2 ), were considered in all patients. A weighted algorithm was used to identify the best mannitol dose for use in the subsequent study., Results: The per-protocol population included 60 patients in the 50 g group, 54 in the 100 g group, and 49 in the 150 g group. The 100 g dose was the best as it afforded optimal colon cleansing efficacy (94.4% of patients had adequate BP), adherence, acceptability, and safety, including negligible gas concentrations., Conclusions: The present study demonstrated that the colon cleansing efficacy and safety of mannitol were dose dependent. Conversely, gas concentrations were not dose dependent and negligible in all patients. Combined evaluation of efficacy, tolerability, and safety, using a weighted algorithm, determined that mannitol 100 g was the best dose for the phase III study., (© 2022. The Author(s).)

This study aimed to define the pharmacokinetics (PKs) of oral mannitol used as an osmotic laxative for bowel preparation for colonoscopy. The PKs of oral mannitol was evaluated in a substudy as part of a phase II dose-finding, international, multicenter, randomized, parallel-group, endoscopist-blinded study. Patients were randomly assigned to take 50, 100, or 150 g mannitol. Venous blood samples were drawn at baseline (T 0 ), 1 h (T 1 ), 2 h (T 2 ), 4 h (T 4 ), and 8 h (T 8 ) after completion of mannitol self-administration. The mean mannitol plasma concentrations (mg/ml) were dose-dependent with a consistent difference among doses. The mean maximum concentration (C max ) ± SD was 0.63 ± 0.15, 1.02 ± 0.28, and 1.36 ± 0.39 mg/ml, in the three dosage groups, respectively. The mean area under the curve from zero to infinity (AUC 0-∞ ) was 2.667 ± 0.668, 4.992 ± 1.706, and 7.403 ± 3.472 mg/ml*h in the 50, 100, and 150 g mannitol dose groups, respectively. Bioavailability was similar in the three dose groups and was just over 20% (0.243 ± 0.073, 0.209 ± 0.081, and 0.228 ± 0.093 in the 50, 100, and 150 g mannitol dose groups, respectively). The present study showed that the bioavailability of oral mannitol is just over 20% and is similar for the three tested doses (50, 100, and 150 g). The linear increase in C max , AUC 0-t8 , and AUC 0-∞ must be considered when choosing the oral mannitol dose for bowel preparation to avoid its systemic osmotic effects., (© 2022 NTC SRL and The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background : Gastrointestinal stromal tumors (GISTs) are most frequently located in the stomach. In the setting of a multidisciplinary approach, surgery represents the best therapeutic option, consisting mainly in a wedge gastric resection. (1) Materials and methods: Between January 2010 to September 2020, 105 patients with a primary gastrointestinal stromal tumor (GISTs) located in the stomach, underwent surgery at three surgical units. (2) Results: A multi-institutional analysis of minimally invasive series including 81 cases (36 laparoscopic and 45 robotic) from 3 referral centers was performed. Males were 35 (43.2%), the average age was 66.64 years old. ASA score ≥3 was 6 (13.3%) in the RS and 4 (11.1%) in the LS and the average tumor size was 4.4 cm. Most of the procedures were wedge resections ( N = 76; 93.8%) and the main operative time was 151 min in the RS and 97 min in the LS. Conversion was necessary in five cases (6.2%). (3) Conclusions: Minimal invasive approaches for gastric GISTs performed in selected patients and experienced centers are safe. A robotic approach represents a useful option, especially for GISTs that are more than 5 cm, even located in unfavorable places.

Objective: To assess the frequency of adverse events associated with periendoscopic management of direct oral anticoagulants (DOACs) in patients undergoing elective GI endoscopy and the efficacy and safety of the British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) recommendations (NCT02734316)., Design: Consecutive patients on DOACs scheduled for elective GI endoscopy were prospectively included. The timing of DOAC interruption and resumption before and after the procedures were recorded, along with clinical and procedural data. Procedures were stratified into low-risk and high-risk for GI-related bleeding, and patients into low-risk and high-risk for thromboembolic events. Patients were followed-up for 30 days for major and clinically relevant non-major bleeding events (CRNMB), arterial and venous thromboembolism and death., Results: Of 529 patients, 38% and 62% underwent high-risk and low-risk procedures, respectively. There were 45 (8.5%; 95% CI 6.3% to 11.2%) major or CRNMB events and 2 (0.4%; 95% CI 0% to 1.4%) thromboembolic events (transient ischaemic attacks). Overall, the incidence of bleeding events was 1.8% (95% CI 0.7% to 4%) and 19.3% (95% CI 14.1% to 25.4%) in low-risk and high-risk procedures, respectively. For high-risk procedures, the incidence of intraprocedural bleeding was similar in patients who interrupted anticoagulation according to BSG/ESGE guidelines or earlier (10.3%vs10.8%, p=0.99), with a trend for a lower risk as compared with those who stopped anticoagulation later (10.3%vs25%, p=0.07). The incidence of delayed bleeding appeared similar in patients who resumed anticoagulation according to BSG/ESGE guidelines or later (6.6%vs7.7%, p=0.76), but it tended to increase when DOAC was resumed earlier (14.4%vs6.6%, p=0.27). The risk of delayed major bleeding was significantly higher in patients receiving heparin bridging than in non-bridged ones (26.6%vs5.9%, p=0.017)., Conclusion: High-risk procedures in patients on DOACs are associated with a substantial risk of bleeding, further increased by heparin bridging. Adoption of the BSG/ESGE guidelines in periendoscopic management of DOACs seems to result in a favourable benefit/risk ratio., Trial Registration Number: NCT02734316; Pre-results., Competing Interests: Competing interests: FR received grants outside the submitted work from BMS/Pfizer and Boehringer Ingelheim. FD received grants outside the submitted work from BMS/Pfizer, Boehringer Ingelheim, Daiichi Sankyo, Roche and Sanofi., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Our main objective was to determine the neuropathological correlates of dementia in patients with Lewy body disease (LBD). Furthermore, we used data derived from clinical, neuropathological and genetic studies to investigate boundary issues between Dementia with Lewy bodies (DLB) and Parkinson's disease with (PDD) and without (PDND) dementia., Methods: One hundred and twenty-one cases with a neuropathological diagnosis of LBD and clinical information on dementia status were included in the analysis (55 PDD, 17 DLB and 49 PDND). We carried out topographical and semi-quantitative assessment of Lewy bodies (LB), Aβ plaques and tau-positive neuropil threads (NT). The APOE genotype and MAPT haplotype status were also determined., Results: The cortical LB (CLB) burden was the only independent predictor of dementia (OR: 4.12, P < 0.001). The total cortical Aβ plaque burden was an independent predictor of a shorter latency to dementia from onset of motor signs (P = 0.001). DLB cases had a higher LB burden in the parietal and temporal cortex, compared to PDD. Carrying at least one APOE ϵ4 allele was associated with a higher cortical LB burden (P = 0.02), particularly in the neocortical frontal, parietal and temporal regions., Conclusions: High CLB burden is a key neuropathological substrate of dementia in LBD. Elevated cortical LB pathology and Aβ plaque deposition are both correlated with a faster progression to dementia. The higher CLB load in the temporal and parietal regions, which seems to be a distinguishing feature of DLB, may account for the shorter latency to dementia and could be mediated by the APOE ϵ4 allele., (© 2015 British Neuropathological Society.)

Background: The addition of impedance to 24-h pH monitoring has allowed detection of weakly acidic reflux, but the extent to which pH-impedance (pH-MII) monitoring improves outcomes is unknown., Methods: This was a prospective observational study. Patients referred for pH or pH-MII monitoring completed a standardized questionnaire on improvement in the dominant symptom, their satisfaction, and treatment at 3 and 12 months after the test during a telephone interview., Results: A total of 184 patients (mean age, 52 years, range, 19-82 years; 35 % with typical symptoms; and 89 % tested off therapy) completed pH (n = 92) or pH-MII monitoring (n = 92) over a period of 15 months. The two arms were similar in terms of demographic, clinical, and endoscopic variables. Ten patients in the pH-MII arm showed evidence of weakly acidic reflux disease. There was no difference in the percentage of patients in the pH and pH-MII monitoring arms who experienced improvement in their dominant symptom after 3 (58 vs. 63 %; p = 0.621) or 12 months (66 vs. 70 %; p = 0.234), and the same was true for patient satisfaction. There were also no between-group difference in the use of proton pump inhibitors (PPIs) after 3 (63 vs. 68.5 %; p = 0.437) or 12 months (47 vs. 60.5 %; p = 0.051). PPIs were prescribed more frequently after a positive test (p < 0.001) although they were used by 45.6 % of the negative patients. Only one patient underwent fundoplication., Conclusions: Two-thirds of patients undergoing pH-MII monitoring experience a positive outcome, similarly to what occurs after traditional pH monitoring. Physicians often pay little attention to the test results, especially if they are negative.

Background: Benign anastomotic colonic stenosis sometimes occur after surgery and usually require surgical or endoscopic dilation. Endoscopic dilation of anastomotic colonic strictures by using balloon or bougie-type dilators has been demonstrated to be safe and effective in multiple uncontrolled series. However, few data are available on safety and efficacy of endoscopic electrocautery dilation. The aim of our study was to retrospectively investigate safety and efficacy of endoscopic electrocautery dilation of postsurgical benign anastomotic colonic strictures., Methods: Sixty patients (37 women; median age 63.6 years, range 22.6-81.7) with benign anastomotic colonic or rectal strictures treated with endoscopic electrocautery dilation between June 2001 and February 2013 were included in the study. Anastomotic stricture was defined as a narrowed anastomosis through which a standard colonoscope could not be passed. Only annular anastomotic strictures were considered suitable for electrocautery dilation which consisted of radial incisions performed with a precut sphincterotome. Treatment was considered successful if the colonic anastomosis could be passed by a standard colonoscope immediately after dilation. Recurrence was defined as anastomotic stricture reappearance during follow-up., Results: The time interval between colorectal surgery and the first endoscopic evaluation or symptoms development was 7.3 months (1.3-60.7). Electrocautery dilation was successful in all the patients. There were no procedure-related complications. Median follow-up was 35.5 months (2.0-144.0). Anastomotic stricture recurrence was observed in three patients who were successfully treated with electrocautery dilation and Savary dilation., Conclusions: Endoscopic electrocautery dilation is a safe and effective treatment for annular benign anastomotic postsurgical colonic strictures.

Background: It has been suggested that multiple rapid swallowing should be added to oesophageal manometry., Aim: To prospectively evaluate whether 10 and 200 mL multiple rapid swallowing provide different information concerning motor function., Methods: 30 consecutive patients with oesophageal symptoms, 13 achalasia patients after successful pneumatic dilation and 19 healthy subjects performed eight 5 mL single swallows, two 10 mL and one 200 mL multiple rapid swallowing., Results: Almost all of the healthy subjects and two-thirds of the patients with oesophageal symptoms showed motor inhibition during both 10 and 200 mL multiple rapid swallowing. The oesophago-gastric pressure gradient was significantly higher during 200 mL multiple rapid swallowing within each group (p < 0.01), and significantly higher in the achalasia patients than in the other two groups (p < 0.0001). Presence of a contraction and increased contraction strength in comparison with single swallows were both more frequent after 10 mL than after 200 mL multiple rapid swallowing in the healthy subjects and the patients (p<0.05)., Conclusion: Motor inhibition could be similarly evaluated by means of 10 and 200 mL multiple rapid swallowing; 10 mL evaluated the after-contraction, whereas 200 mL multiple rapid swallowing was more valuable in identifying increased resistance to outflow., (Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. All rights reserved.)

Background/aims: Symptom reflux association analysis is especially helpful for evaluation and management of proton pump inhibitor (PPI) re-fractory patients. An accurate calculation requires manual editing of 24-hour multichannel intraluminal impedance-pH (MII-pH) tracings after automatic analysis. Intra- and inter-observer agreement as well as reliability of rapid editing confined to the time around symptomatic episodes are unknown. Aim of this study was to explore these topics in a prospective multicenter study., Methods: Forty consecutive patients who were off PPI therapy underwent MII-pH recordings. After automatic analysis, their tracings were anonymized and randomized. Three experienced observers, each one trained in a different European center, independently per-formed manual editing of 24-hour tracings on 2 separate occasions. Values of symptom index and symptom association proba-bility for acid and non acid reflux were transformed into binary response (i.e., positive or negative)., Results: Intra-observer agreement on symptom reflux association was 92.5% to 100.0% for acid and 85.0% to 97.5% for non-acid reflux. Inter-observer agreement was 100.0% for acid and 82.5% to 95.0% for non-acid reflux. Values for symptom index and symptom association probability were similar. Concordance between 24-hour and rapid (2 minutes-window before each symp-tomatic episode) editings for symptom reflux association occured in 39 to 40 patients (acid) and in 37 to 40 (non-acid), de-pending on the observer., Conclusions: Intra- and inter-observer agreement in classifying patients with or without symptom reflux association at manual editing of 24-hour tracings was high, especially for acid reflux. Classifying patients according to a rapid editing showed excellent con-cordance with the 24-hour one and can be adopted in clinical practice.

Background/aims: Swallowing of cold liquids decreases amplitude and velocity of peristalsis in healthy subjects, using standard manometry. Patients with achalasia and non obstructive dysphagia may have degeneration of sensory neural pathways, affecting motor response to cooling. To elucidate this point, we used high-resolution manometry., Methods: Fifteen healthy subjects, 15 non-obstructive dysphagia and 15 achalasia patients, after pneumatic dilation, were studied. The 3 groups underwent eight 5 mL single swallows, two 20 mL multiple rapid swallows and 50 mL intraesophageal water infusion (1 mL/sec), using both water at room temperature and cold water, in a randomized order., Results: In healthy subjects, cold water reduced distal contractile integral in comparison with water at room temperature during single swallows, multiple rapid swallows and intraesophageal infusion (ratio cold/room temperature being 0.67 [95% CI, 0.48-0.85], 0.56 [95% CI, 0.19-0.92] and 0.24 [95% CI, 0.12-0.37], respectively). A similar effect was seen in non-obstructive dysphagia patients (0.68 [95% CI, 0.51-0.84], 0.69 [95% CI, 0.40-0.97] and 0.48 [95% CI, 0.20-0.76], respectively), whereas no changes occurred in achalasia patients (1.06 [95% CI, 0.83-1.29], 1.05 [95% CI, 0.77-1.33] and 1.41 [95% CI, 0.84-2.00], respectively)., Conclusions: Our data suggest impairment of esophageal reflexes induced by cold water in patients with achalasia, but not in those with non obstructive dysphagia.

The following paper on functional testing of the pharynx includes commentaries on the use of 24-h pH-impedance testing to identify patients with nonacid reflux and the caveats associated with automatic and visual analysis; the potential diagnostic yield of ambulatory high-resolution manomentry (HRM), particularly in identifying non-cardiac chest pain and transient lower esophageal sphincter relaxations; the differential manometric identification of conditions facilitated by using solid swallows, and the advantages of the newly developed ResTech oropharyngeal pH probe in the detection of proximal reflux events., (© 2013 New York Academy of Sciences.)

Background: Transient lower esophageal sphincter relaxation (TLESR) is a vagally mediated reflex that occurs most frequently after a meal. Cardiac vagal tone (CVT) decreases after a meal, and correlates with changes in gastric electrical activity. Furthermore, decreased CVT has been reported in patients with gastro-esophageal reflux disease. We therefore aimed to characterize the association between postprandial changes in CVT and the occurrence of TLESR and reflux., Methods: Ten healthy volunteers underwent simultaneous autonomic nervous system, gastric myoelectric activity, lower esophageal-sphincter pressure, and reflux monitoring for 30 min in the fasting state, followed by a standard meal, and a further 4 h postprandially. Results are in mean ± SEM., Key Results: The number of TLESRs (P < 0.0001) and reflux episodes (P < 0.0001) increased after the meal, while CVT decreased (P < 0.01). Cardiac sensitivity to baroreceptor reflex (CSB) showed similar time course changes to CVT (P = 0.06). During the first postprandial hour there was a strong correlation between the number of TLESRs and reflux episodes with CVT (R(2)  = 0.51 and R(2)  = 0.50, respectively; P < 0.05). There was also an increase in the dominant power and power ratio on electrogastrography (P < 0.05) after the meal., Conclusions & Inferences: In healthy volunteers, the increase in the number of TLESRs and reflux episodes after a meal occurred mostly at a time of reduced CVT. Further studies should explore whether modulation of CVT can modify frequency of TLESRs and also this relationship should be further explored in patients with reflux disease., (© 2013 John Wiley & Sons Ltd.)

Background & Aims: Many patients with gastroesophageal reflux disease (GERD) have persistent reflux despite treatment with proton pump inhibitors (PPIs). Mixed gas-liquid reflux events are more likely to be perceived as symptomatic. We used esophageal impedance monitoring to investigate whether esophageal gas is processed differently among patients with GERD who do and do not respond to PPI therapy., Methods: We performed a prospective study of 44 patients with typical reflux symptoms with high levels of esophageal acid exposure during a 24-hour period; 18 patients were fully responsive, and 26 did not respond to PPI therapy. Twenty-four-hour pH impedance recordings were analyzed for fasting and prandial air swallows and reflux characteristics, including the presence of gas in the refluxate., Results: PPI-refractory patients had a higher number (83.1 ± 12.7 vs 47.8 ± 7.3, P < .05) and rate (10.5 ± 1.4 vs 5.9 ± 0.8/10 minutes, P < .05) of prandial air swallows than patients who responded to PPI therapy; they also had a higher number (25.5 ± 4.0 vs 16.8 ± 3.3, P < .05) and proportion (70% ± 0.03% vs 54% ± 0.06%, P < .05) of postprandial, mixed gas-liquid reflux. Symptoms of PPI-refractory patients were more often preceded by mixed gas-liquid reflux events than those of PPI responders. Fasting air swallowing and other reflux characteristics did not differ between patients who did and did not respond to PPIs., Conclusions: Some patients with GERD who do not respond to PPI therapy swallow more air at mealtime than those who respond to PPIs and also have more reflux episodes that contain gas. These factors, combined with mucosal sensitization by previous exposure to acid, could affect perception of symptoms. These patients, who can be identified on standard 24-hour pH impedance monitoring, might be given behavioral therapy to reduce mealtime air swallowing., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)

We report a 66-year-old man with a spinal, extradural solitary fibrous tumor showing unique retiform and papillary architecture. The patient presented in May 2008 with worsening right-sided lower back pain and urinary frequency. Magnetic resonance imaging of the spine documented a heterogeneously enhancing dumbbell-shaped extradural lesion causing cord compression at T11/12 level. The tumor extended to the paravertebral soft tissue and invaded the right adjacent vertebral pedicles and laminae. An angiogram showed prominent vascular supply mainly from the right T11 radicular artery. The patient underwent surgery to relieve cord compression in May 2008 and a second operation following embolization with coils in October 2009. No recurrence was observed at the last neuroimaging follow-up in June 2012. The tumor was composed of vimentin, CD34, Bcl-2, and CD99-positive rounded or slightly elongated cells with scant cytoplasm and oval to spindle nuclei. Several pseudovascular spaces reminiscent of the rete testis were present, and several of them contained papillary projections. Cytologic atypia was minimal, and mitotic activity was low. Focal infiltration of the paraspinal adipose tissue was seen at microscopic level. To our knowledge, retiform and papillary features have never been reported in a solitary fibrous tumor., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Aims: The aim of this study is to evaluate the pathological features, serum hormone levels and ex vivo cultures of pituitary adenomas that occur in rats affected by MENX syndrome. MENX is multiple endocrine neoplasia syndrome caused by a germline mutation in the cell cycle inhibitor p27. Characterization of MENX adenomas is a prerequisite to exploit this animal model for molecular and translational studies of pituitary adenomas., Methods: We investigated MENX pituitary adenomas with immunohistochemistry, double immunofluorescence, electron microscopy, reverse transcription polymerase chain reaction (RT-PCR), measurement of serum hormone levels and ex vivo cultures., Results: Adenomas in MENX rats belong to the gonadotroph lineage. They start from 4 months of age as multiple neoplastic nodules and progress to become large lesions that efface the gland. Adenomas are composed of chromophobic cells predominantly expressing the glycoprotein alpha-subunit (αGSU). They show mitotic activity and high Ki67 labelling. A few neoplastic cells co-express gonadotropins and the transcription factor steroidogenic factor 1, together with growth hormone or prolactin and Pit-1, suggesting that they are not fully committed to one cell lineage. Ex vivo cultures show features similar to the primary tumour., Conclusions: Our results suggest that p27 function is critical to regulate gonadotroph cells growth. The MENX syndrome represents a unique model to elucidate the physiological and molecular mechanisms mediating the pathogenesis of gonadotroph adenomas., (© 2012 The Authors. Neuropathology and Applied Neurobiology © 2012 British Neuropathological Society.)

Background: Few data are available comparing intragastric pH measured with the traditional catheter-based and the more recent wireless system (Bravo), and also comparing intraesophageal and intragastric pH during reflux events. Aims of our study were to elucidate these points., Methods: Eleven subjects with functional dyspepsia underwent placement of a Bravo capsule 9 cm below the squamo-columnar junction (SCJ) and of a dual-electrode catheter, so that the distal electrode was located 9 cm below and the proximal one 6 cm above the SCJ., Key Results: The wireless system showed lower intragastric pH than the traditional catheter in the postprandial period (median 2.2 wireless vs 2.7 catheter, P < 0.05) but not in the whole 24 h. Moreover, during the 24 h, minimum intraesophageal pH during reflux events was lower than the simultaneous pH in the gastric body recorded using the catheter (2.2 vs 2.4, P < 0.01) and in the postprandial period lower than the one recorded using both techniques (2.3 vs 2.8 wireless and 3.2 catheter, P < 0.001)., Conclusions & Inferences: (i) after meals, in the 1st 2 h postprandial pH in the gastric body is significantly lower when measured with the wireless capsule than with the traditional catheter, presumably because of less buffering by food in proximity of the mucosa, (ii) during reflux events intraesophageal pH is lower than pH in the gastric body, in accordance with the notion of greater intragastric acidity in the subcardial region., (© 2012 Blackwell Publishing Ltd.)

Background: We investigated whether tigecycline (TIGE) is more effective than talc in inducing pleurodesis in rabbits., Methods: Fifty-six New Zealand rabbits were utilized in a two-phase study: Effects at 14 d (phase I) and at 28 d (phase II) were assessed. Saline solution (SAL n = 3), talc slurry (TALC 200 mg/kg, n = 5), and TIGE at different concentrations (mg/kg): TIGE0.5 (n = 5); TIGE1 (n = 5); TIGE3 (n = 5); TIGE25 (n = 5); TIGE50 (n = 5) were randomly injected, for each phase, through a right chest drainage. TIGE0.5 and TIGE1 were ineffective during phase I and were thus excluded from further investigation. At post mortem examination, pleurodesis was graded grossly and microscopically by three observers blinded to treatment groups., Results: Phase I: pleurodesis was more effective in TIGE25 and TIGE50 (P < 0.001); TALC was better than TIGE0.5 (P < 0.001), and TIGE1 (P = 0.49), macroscopically. Pleural thickness was significantly higher in TIGE25 compared with SAL, TALC, TIGE0.5, TIGE1, and TIGE3 (P < 0.01). No significant differences were evident between TALC and TIGE3, both macroscopically (P = 0.90) and microscopically (inflammation P = 0.99, fibrosis P = 0.96, pleural thickness P = 0.99). Phase II: better effectiveness of TIGE50 compared with all other groups (P < 0.001) except TIGE 25 (P = 0.29); results similar to phase I for TALC and TIGE3 (P = 0.99), macroscopically. Microscopically greater inflammation in TALC compared with TIGE3 (P < 0.05) and in TIGE50 to TIGE3 (P = 0.05). Significant complications occurred in all TIGE50 group. One of TIGE25 and one of TIGE50 died of respiratory distress and of right hemothorax+ascites, respectively., Conclusions: Intrapleural TIGE3 mg/kg is as effective as talc in inducing pleurodesis in rabbits. The intrapleural TIGE toxicity threshold was reached at TIGE25 mg/kg concentration., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The diffuse variant of supravalvular aortic stenosis (SVAS) is one of the most rare congenital vascular pathological conditions of adulthood. Due to its rarity, surgical treatment of this clinical entity is still a matter of debate because of the variable degree of aortic narrowing, presence of multilevel obstruction, and age at presentation, all factors that strongly influence the disease prognosis. We report a case of an adult patient with an extremely calcified diffuse SVAS who underwent successful replacement of the ascending aorta through the interposition of a tubular prosthesis. Six months' follow-up showed complete relief of the aortic gradient and an improvement in clinical performance.

Aim: Biliary leaks are widely reported complications of cholecystectomy, but standard management remains undecided. The objective of our study was to report the role of symptoms, biochemical tests, and ERCP in patients with a leak., Materials and Methods: Twenty-one patients (8 M, 26-77 years) with suspected post-cholecystectomy biliary leak were retrospectively studied. Symptoms and liver tests (LTs) after surgery were monitored. Trends of LTs were considered positive if increases at >48 h were seen. ERCP was performed in all patients. Findings at endoscopy and treatments were reported. Outcome results were obtained for all patients., Results: Seventeen of 21 patients had persistent biliary leak at ERCP, because of direct injury (n = 10), accessory duct (n = 4), or cystic duct stump (n = 3). Eleven of 17 patients (six without symptoms), had distal obstruction because of surgical injury (n = 8), stone (n = 2), or cholangiocarcinoma (n = 1) and underwent stenting (n = 4), naso-biliary drainage, NBD (n = 3), or surgery (n = 4). Among the six patients without obstruction (four without symptoms), stenting was performed in two and NBD in four. The four patients without apparent leak underwent NBD. Impairment of LTs was present in ten out of eleven (91%) patients with obstruction versus six of ten (60%) without obstruction. No complications occurred after ERCP. During a median follow-up of 33 months (cholangiocarcinoma excluded) all but one remained asymptomatic., Conclusions: Symptoms and trend of LTs were not predictive of biliary obstruction in patients with a leak after cholecystectomy. Both endotherapy and surgery had favorable outcomes.

Objective: To get insight into usefulness of 96-h wireless monitoring in diagnosis of gastro-esophageal reflux disease (GERD) and in patients' management., Material and Methods: 51 patients who underwent 96-h wireless and 51 matched patients who underwent 24-h traditional pH monitoring were enrolled and retrospectively contacted with a structured telephone interview., Results: In the wireless group, the 96-h recording improved (p < 0.05) the diagnostic yield compared with the first 48-h recording by allowing Symptom Association Probability to be measured in eight more patients and by decreasing indeterminate tests from 11 to 5. After pH monitoring, concordance between results of the test and treatment for GERD was higher in the wireless compared with the traditional group, 78% versus 58% of the patients (p < 0.05). Both improvement/disappearance of the clinically relevant symptom and satisfaction (score of 1-10) at time of the telephone interview were however similar in the two groups, 73% versus 65% and 7.0 versus 6.5., Conclusions: Wireless pH monitoring prolonged to 96 h increased the likelihood to exclude/confirm GERD as the cause of the clinically relevant symptoms in those patients with an indeterminate result for GERD after the first 48 h. Outcome was however similar to the one of traditional pH monitoring.

Delayed gastric emptying in a variable proportion of patients with gastro-oesophageal reflux disease has been observed in most series, however a relationship between delayed gastric emptying and increased gastro-oesophageal reflux has not been convincingly demonstrated. Enhanced postprandial accommodation and delayed emptying of the proximal stomach have been described, but some controversy exists. Impaired primary peristalsis is often present especially in patients with oesophagitis and its prevalence increases with increasing severity of inflammatory mucosal lesions. Patients with gastro-oesophageal reflux disease often have defective triggering of secondary peristalsis independently of presence of oesophagitis. It is presently unclear if impaired oesophageal motility is a primary defect or an irreversible consequence of inflammation. Attempts at pharmacological improvement of impaired oesophageal motility have been so far disappointing. Patients with partially preserved neuromuscular structures need to be identified in order to select them for new prokinetic therapy., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background: Long-term follow-up studies of achalasia after pneumatic dilation, mostly retrospective, have shown variable results., Aim: To examine the outcome of achalasia after pneumatic dilation using a prospective follow-up programme., Methods: One or two dilations (first dilation treatment) in 77 patients to achieve stable (>1 year) remission and patients followed up with yearly clinical and manometric assessments. Endoscopy, pH monitoring and barium swallow were also performed., Results: A total of 69 patients achieved stable remission and were followed up for 5.6 years (3-10.7) [median (IQ range)], whereas six patients underwent cardiomyotomy and two experienced a perforation. Twelve of the 69 patients relapsed after 2.6 years (1.7-5.1): nine of 12 underwent one to two further dilations. Six-year remission rate (by Kaplan-Meyer estimates) was 82% after first dilation treatment and 96% after all dilations. Continuous antisecretory treatment was clinically needed in 16%, oesophagitis present in 7% and reflux pathological in 28% of the patients. Beneficial effects of dilation on oesophageal motility and on diameter of the oesophageal body at barium swallow were maintained during follow-up., Conclusions: A management strategy including sessions of pneumatic dilation until stable remission and a standardized follow-up is highly successful in the long term. Gastro-oesophageal reflux is clinically relevant in a minority of patients.

Background: In the era of screening colonoscopy, assessment of operator competence is warranted., Aim: To evaluate feasibility of a computer simulator (CS) use for assessment of competence in colonoscopy by investigating performance of expert endoscopists at CS., Subjects: Twenty expert endoscopists involved in screening colonoscopy., Methods: Experts returned a questionnaire regarding personal practice (duration of activity, number of colonoscopies in the last year and assistance by a nurse) and performances (percentage of caecal intubation and polyp detection rate). One easy and one difficult colonoscopy were proposed at CS in randomized order., Results: Participation rate was 75%. Caecal intubation rate in clinical practice was more than 90% for all experts. At CS, time to caecal intubation and number of attempts for ileal intubation were significantly lower during easy versus difficult colonoscopy (P<0.01 for both items); interestingly, percentage of mucosa explored was higher (P<0.05) during the difficult simulation. Withdrawal time >/=6 min was achieved by 40 and 33% of experts during the easy and difficult simulation, respectively. Independent of simulation difficulty, time with loop was lower (P<0.05) for experts using hands-free insertion (n = 8) compared with those using nurse assistance in their clinical practice (n = 7). No correlation was found between scores at CS and performance in clinical practice., Conclusion: Scores at CS are sensitive to the rate of technical difficulty and nurse assistance during daily practice. Withdrawal time is often shorter than required for high accuracy in polyp detection. CS could be a well-accepted tool for assessment of competence.

Objectives: After meals, highly acidic gastric juice is present in the subcardial region, the so-called acid pocket. Patients with gastroesophageal reflux disease (GERD) have a higher frequency of acidic reflux. Our aim was to investigate the possible differences in subcardial pH in GERD over 24 h and the role of hiatal hernia (HH), using a wireless capsule., Methods: A total of 14 healthy volunteers (4 men, 24-60 years), 10 GERD patients without HH (4 men, 25-68 years), and 11 GERD patients with HH >or=3 cm (2 men, 46-74 years) underwent 24-h wireless pH monitoring 2 cm below the squamocolumnar junction. All patients had increased 24-h acid reflux. A standardized lunch was given to all study subjects., Results: No capsule detached during the 24-h recording. Median 24-h pH was similar in healthy subjects, and in patients without and with HH, median: 1.4 (interquartile range: 1.2 -1.9), 1.5 (1.3 -1.7), and 1.4 (1.3 -1.7), respectively. Similar results were seen in the supine period. Median pH after the standardized meal was often highly acidic, 2.7 (1.5 - 3.2), 1.9 (1.6 - 2.3), and 2.5 (1.6 - 3.2), respectively. The first minute with a median pH <2 occurred 14 min (4 - 49), 14 min (6 - 25), and 20 min (4 - 43), respectively, P=NS, after the end of the meal. Similar data were observed on pooling all meals together., Conclusions: Subcardial pH is confirmed to be highly acidic early after meals, but it is similar over 24 h in healthy subjects and GERD patients independent of the presence of HH.

The authors present a case of heterotopic central nervous system tissue observed in an 81-year-old male in the form of an ethmoidal polyp. A review of the literature indicates that this is a rare condition characterised by a connective tissue lesion with astrocytic and oligodendrocytic glial cells, which may be located outside the nasal pyramid in some cases and inside the nasal cavity in others. The most important diagnostic aspect involves differentiating these from meningoencephalocele, which maintains an anatomical connection with central nervous system tissue. Contrast-enhanced imaging is essential for diagnosis, as in cases of heterotopic central nervous system tissue, it will demonstrate that there are no connections with intra-cranial tissue. Endoscopic excision is the treatment of choice.

Multiple rapid swallowing (MRS) stimulates neural inhibition resulting in abolition of contractions in the oesophageal body (OB) and complete lower oesophageal sphincter (LOS) relaxation which is followed by peristalsis and LOS contraction. The aim of this study was to evaluate the yield of MRS to detect abnormalities in inhibitory or excitatory oesophageal mechanisms in patients with oesophageal symptoms and either normal standard manometry or ineffective oesophageal motility (IOM). MRS (five water swallows, 2 mL, separated by 2-3 s) was evaluated in 23 healthy subjects, 109 symptomatic patients with normal standard sleeve manometry and in 48 patients with IOM. Healthy subjects had complete inhibition of OB motility during MRS and a strong motor response after MRS, i.e. amplitude of OB contractions in the oesophageal body and LOS tone being higher than after single swallows. Almost 70% of patients with oesophageal symptoms and normal manometry had abnormal MRS, mainly consistent on inability to increase amplitude of OB contractions after MRS. Nearly, half of the patients with IOM were able to normalize OB contractions after MRS. MRS is a simple complementary test that can be added to standard oesophageal manometry. Two-thirds of patients with normal manometry show abnormal MRS that could potentially underlie their symptoms. A normal response to MRS in patients with severe IOM might be used to predict response to prokinetic treatment.

A 54-year-old male, non smoker, began to suffer from persistent dyspnoea and fever. X-ray and CT scan showed a cystic lesion located in the left anterior mediastinum. This lesion was removed instead of the initially scheduled surgical resection with video-assisted thoracoscopic surgery (VATS) preceded by fine needle aspiration (FNA). A diagnosis of thymoma arising in the wall of thymic cyst was made. Such a rare tumour should be taken into consideration in treating patients with a cystic mediastinal lesion, before VATS and FNA.

Background: Twenty-four hours oesophageal pH monitoring is considered the reference-standard for the diagnosis of gastro-oesophageal reflux disease, but it is limited by catheter discomfort and limitations of daily habits., Aim: We evaluated tolerability and impact on food intake and daily activities of catheter-based compared to wireless pH monitoring., Patients: One-hundred and thirty-three consecutive patients with suspected gastro-oesophageal reflux disease were enrolled., Methods: Seventy-eight patients (36 M, 53+/-2 years) underwent the 24 h catheter-based and 55 patients (25 M, 44+/-3 years) the 48 h wireless pH monitoring. Discomfort at placement and during the test was evaluated by 100 mm visual analogue scales. Limitations of food intake and of daily activities were evaluated by standardized questionnaires (score 0 to 3)., Results: Discomfort (mean+/-standard error of the mean) at placement and during the test was 32+/-3 versus 29+/-4 (p=ns) and 37+/-3 versus 22+/-3 (p<0.001) for the catheter-based versus wireless techniques. Limitation of food intake and of daily activities (mean+/-standard error of the mean) were 0.9+/-0.1 versus 0.4+/-0.1 (p<0.05) and 1.2+/-0.1 versus 0.2+/-0.1 (p<0.0001), respectively., Conclusions: The wireless pH monitoring is better tolerated and has minor impact on daily habits compared to the traditional technique. Whether this translates into better diagnostic accuracy remains to be evaluated.