The TANDEM investigation: efficacy and tolerability of levodopa-carbidopa intestinal gel in (LCIG) advanced Parkinson's disease patients.

The TANDEM investigation was carried out in 17 Italian Movement Disorder centers on behalf of a joint initiative of neurologist members of the Italian Academy for Parkinson's disease and Movement Disorders (LIMPE-DISMOV Academy) and gastroenterologist members of the Italian Society of Digestive Endoscopy (SIED) to evaluate the efficacy and tolerability of levodopa-carbidopa intestinal gel (LCIG) in patients with advanced Parkinson's disease (PD) in routine medical care. Motor scores in "ON" and OFF" state (UPDRS-III), complications of therapy (UPDRS-IV), activities of daily living, sleep disorders and quality of life were evaluated at baseline and at two follow-up assessments (FUV1 and FUV2) within the initial 12-month LCIG treatment. In 159 patients (55% males) with a mean age of 69.1 ± 6.6 years and a diagnosis of PD since 13.6 ± 5.5 years, the UPDRS-III total score (in "OFF") decreased from baseline (45.8 ± 13.2) to FUV1 (41.0 ± 17.4; p < 0.001) and FUV2 (40.5 ± 15.5; p < 0.001), the UPDRS-IV total score decreased from baseline (8.8 ± 2.9) to FUV1 (5.1 ± 3.4; p < 0.001) and FUV2 (5.5 ± 3.2; p < 0.001). The percentage of patients exhibiting freezing, dystonia, gait/walking disturbances, falls, pain and sleep disorders was significantly reduced. Twenty-eight device complications were reported and 11 (6.9%) patients prematurely terminated the study. LCIG after 12-month treatment led to sustained improvement of time spent in "OFF", complications of therapy, PD-associated symptoms and sleep disorders. LCIG tolerability was consistent with the established safety profile of LCIG.

The importance of a second opinion in the diagnosis of Barrett’s esophagus: a 'real life' study

Background: Barrett's esophagus is a precancerous lesion, and its identification with the early detection of dysplasia is of paramount importance to prevent adenocarcinoma onset. However, there is still debate on the correct pathological identification of Barrett’s esophagus (and of associated dysplasia), and most studies have been conducted in an experimental setting. Aims: To assess previous uncertain diagnoses of Barrett’s (with and without dysplasia) via a second opinion of an expert pathologist in a real life setting. Patients and methods: Histological sections of 32 suspected Barrett’s patients from ten general Pathology units were centralized into one single unit in which an expert pathologist reviewed the slides blindly. Results: Overall, in 78% of cases there was diagnostic discordance; in particular, in 64% of cases the presence of low grade dysplasia was not confirmed. Of interest, 28% of cases with the original diagnosis were reclassified as non-Barrett’s. Conclusions: The pathological diagnosis of Barrett’s esophagus, especially with regard to the presence of dysplasia, is still misinterpreted, particularly in the setting of general pathology units. Thus, a second opinion from an experienced pathologist may help in the interpretation of the results and in starting appropriate followup programs (AU)

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The importance of a second opinion in the diagnosis of Barrett's esophagus: a "real life" study.

BACKGROUND: Barrett's esophagus is a precancerous lesion, and its identification with the early detection of dysplasia is of paramount importance to prevent adenocarcinoma onset. However, there is still debate on the correct pathological identification of Barrett's esophagus (and of associated dysplasia), and most studies have been conducted in an experimental setting. AIMS: To assess previous uncertain diagnoses of Barrett's (with and without dysplasia) via a second opinion of an expert pathologist in a real life setting. PATIENTS AND METHODS: Histological sections of 32 suspected Barrett's patients from ten general Pathology units were centralized into one single unit in which an expert pathologist reviewed the slides blindly. RESULTS: Overall, in 78% of cases there was diagnostic discordance; in particular, in 64% of cases the presence of low grade dysplasia was not confirmed. Of interest, 28% of cases with the original diagnosis were reclassified as non-Barrett's. CONCLUSIONS: The pathological diagnosis of Barrett's esophagus, especially with regard to the presence of dysplasia, is still misinterpreted, particularly in the setting of general Pathology units. Thus, a second opinion from an experienced pathologist may help in the interpretation of the results and in starting appropriate follow-up programs.

A pilot study assessing tolerance safety and feasibility of diagnostic transnasal esophagogastroduodenoscopy using an improved larger caliber endoscope and an adapted topical anesthesia.

BACKGROUND: Transnasal esophagogastroduodenoscopy (TN-EGDS) is well tolerated by patients and the examination is perceived comfortable without the need of a sedative drug. Conversely, mainly in Western literature, some authors report limitations in illumination, image quality, and working channel as affecting TN-EGDS diffusion. To overcome these disadvantages, a new transnasal endoscope (TNE) was tested but, due to its larger diameter, we have no evidence of its clinical safety and tolerability. A new adapted nasal anesthesia could be useful to improve TNE tolerance. In an independent, not sponsored, pilot prospective study we enrolled, in a busy clinical hospital setting, 30 adult patients receiving nasal atomized Lidocaine and Xylometazoline (XAL) to undergo a diagnostic TN-EGDS with TNE to evaluate its tolerance, safety, and feasibility. METHODS: Three physicians enrolled inpatients and outpatients with indication to diagnostic EGDS during a 6-month period. Main outcome measures were cardio-pulmonary monitoring data and patients' answers to an adapted questionnaire investigating pain, anxiety level, willingness to repeat the examination, operators' scores about endoscopy quality, examination conduction and anesthesia-related complications. RESULTS: The examination was completed by the transnasal route in 100 % of the enrolled patients, endoscopy satisfaction and feasibility were scored to nearly the highest levels by the three different physicians. A total of 29/30 patients (96.6 %) declared the willingness to repeat the same examination if needed. The mean patients' score for overall pain was 3.7 ± 1 SD (range 1-10 by Visual Analog Scale). Mean endoscopy duration was 11.1 ± 2.6 min (range 5.0-19.0). In a total of 17/30 TN-EGDS that lasted more than 11 min, higher heart frequency variations and worse tolerance scores were found (p < 0.05). CONCLUSION: Our pilot study demonstrates that TN-EGDS with TNE and NA is safe, well tolerated, and feasible. The best clinical tolerance is reached when TN-EGDS lasts <11 min.

Rectal laterally spreading tumors successfully treated in two steps by endoscopic submucosal dissection and endoscopic mucosal resection.

BACKGROUND: Endoscopic submucosal dissection (ESD) is an advanced technique of therapeutic endoscopy alternative to endoscopic mucosal resection (EMR) for superficial gastrointestinal neoplasms >2 cm. ESD allows for the direct dissection of the submucosa and large lesions can be resected en bloc. ESD is not limited by resection size, increases histologically complete resection rates and may reduce the local recurrence. Nevertheless, the technique is time-consuming, technically demanding and associated with a high complication rate. To reduce the risk of complications, different devices and technical advances have been proposed with conflicting results and, still, ESD en bloc resections of huge lesions are associated with increased complications. CASE PRESENTATION: We successfully used a combined ESD/EMR technique for huge rectal laterally spreading tumors (LSTs). ESD was used for circumferential resection of 2/3 of the lesion followed by piecemeal resection (2-3 pieces) of the central part of the tumour. In all three patients we obtained the complete dissection of the polyp and the complete histological evaluation in absence of complications and recurrence at 6 months' follow up. CONCLUSIONS: In the treatment of rectal LSTs, the combined treatment - ESD/EMR resection may be considered a suitable therapeutic option, indicated in selected cases as an alternative to surgery, in which the two techniques are neither reliable nor safe separately. However, to confirm our results, larger trials with longer follow up are required together with improvement of the technique and of the technical devices.

Effective bowel cleansing before colonoscopy: a randomized study of split-dosage versus non-split dosage regimens of high-volume versus low-volume polyethylene glycol solutions.

BACKGROUND: Adequate bowel cleansing is essential for a high-quality, effective, and safe colonoscopy. OBJECTIVES: To evaluate the degree of colon cleansing comparing split-dosage versus non-split-dosage intake of two different polyethylene glycol (PEG) volumes (low-volume PEG + ascorbic acid vs standard-volume PEG-electrolyte solution) and to identify predictors of poor bowel cleansing. DESIGN: Single-blind, active control, randomized study. SETTING: Tertiary-care institutions in Italy. PATIENTS: This study involved adult patients undergoing elective colonoscopy. INTERVENTION: Colonoscopy with different bowel preparation methods. MAIN OUTCOME MEASUREMENTS: Degree of bowel cleansing. RESULTS: We randomized 895 patients, and 868 patients were finally included in intention-to-treat (ITT) analysis. Overall compliance was excellent (97%) for both preparation methods. No difference in tolerability was recorded. Palatability was superior with low volume compared with high volume (acceptable or good 58% vs 51%, respectively, P < .005), independently of intake schedule. PEG plus ascorbic acid produced the same degree of cleansing as standard-volume PEG-electrolyte solution (77% vs 73.4%, respectively, within the split-dosage group and 41.7% vs 44.3%, respectively, within the non-split-dosage group). Independently of PEG volumes, the split-dosage regimen produced markedly superior cleansing results over the same-day method (good/excellent 327/435, 75.2% vs 186/433, 43.0%, P = .00001). Maximum cleansing was observed in colonoscopies performed within 8 hours from the last fluid intake versus over 8 hours from the last fluid intake (P < .001). The degree of bowel cleansing affected both cecal intubation (failed intubation 11.7% with fair/poor preparation vs 1.2% with good/excellent preparation, P = .00001) and polyp detection rates (12.2% with fair/poor vs 24.6% with good/excellent preparation, P = .001). Aborted procedures were significantly more frequent in the non-split-dosage arm (21.2% vs 6.9%, odds ratio [OR] 3.60 [2.29-5.77], P < .0001). Independent predictors of poor bowel cleansing were male sex (OR 1.45 [1.08-1.96], P = .014) and a non-split-dosage bowel preparation schedule (OR 2.08 [1.89-2.37], P = .0001). CONCLUSION: Low-volume PEG plus ascorbic acid is as effective as high-volume PEG-electrolyte solution but has superior palatability. A split-dosage schedule is the most effective bowel cleansing method. Colonoscopy should be performed within 8 hours of the last fluid intake.

Ten and eight-day sequential therapy in comparison to standard triple therapy for eradicating Helicobacter pylori infection: a randomized controlled study on efficacy and tolerability.

BACKGROUND: Sequential therapy (SQT) is effective in the eradication of Helicobacter pylori and could become an alternative to standard triple therapy (STT). AIM: To compare the efficacy and tolerability of SQT, for either 8 or 10 days, with a 7-day STT. METHODS: A total of 270 naive H. pylori-positive patients were randomized to receive: SQT for 8 days (SQT-8, n=90) or 10 days (SQT-10, n=90) including esomeprazole 20 mg twice daily (bid) associated with amoxicillin 1000 mg bid (early 4 and 5 d, respectively), followed by esomeprazole 20 mg bid associated with clarithromycin 500 mg bid plus tinidazole 500 mg bid (last 4 and 5 d, respectively); STT (n=90) including esomeprazole 20 mg bid plus amoxicillin 1000 mg bid and clarithromycin 500 mg bid for 7 days. Tolerability was assessed by scoring the severity of symptoms. RESULTS: Eradication rates after SQT-8 and SQT-10 were higher than that of after STT at both intention-to-treat (83% and 86% vs. 66%, P<0.02) and per-protocol analysis (90% and 88% vs. 75%, P<0.05), whereas no difference was found between the 2 SQTs. CONCLUSIONS: This study shows that SQT, for 8 or 10 days, is well tolerated and highly effective in H. pylori eradication and could represent a valid alternative to STT. Further studies, with more power, on larger populations and from other countries are necessary to validate the present findings.

Look out before polypectomy in patients with diverticular disease--a case of a large, inverted diverticulum of the colon resembling a pedunculated polyp.

Diverticular disease of the colon may be responsible for abdominal symptoms requiring colonoscopy, which may reveal the presence of concomitant polyps. A polyp found during colonoscopy in patients with colonic diverticular disease may be removed by endoscopic polypectomy with electrosurgical snare, a procedure associated with an incidence of perforation of less than 0.05%. The risk of such a complication may be higher in the event of an inverted colonic diverticulum, which may be misinterpreted as a polypoid lesion at colonoscopy. To date, fewer than 20 cases of inverted colonic diverticula, diagnosed at colonoscopy or following air contrast barium enema, have been reported in the literature. The present report describes a 68-year-old woman who underwent a screening colonoscopy, which revealed a voluminous pedunculated polyp that was recognized to be an inverted giant colonic diverticulum before endoscopic polypectomy.

Predicting mortality in non-variceal upper gastrointestinal bleeders: validation of the Italian PNED Score and Prospective Comparison with the Rockall Score.

OBJECTIVES: We sought (i) to validate a new prediction rule of mortality (Progetto Nazionale Emorragia Digestiva (PNED) score) on an independent population with non-variceal upper gastrointestinal bleeding (UGIB) and (ii) to compare the accuracy of the Italian PNED score vs. the Rockall score in predicting the risk of death. METHODS: We conducted prospective validation of analysis of consecutive patients with UGIB at 21 hospitals from 2007 to 2008. Outcome measure was 30-day mortality. All the variables used to calculate the Rockall score as well as those identified in the Italian predictive model were considered. Calibration of the model was tested using the chi2 goodness-of-fit and performance characteristics with receiver operating characteristic (ROC) analysis. The area under the ROC curve (AUC) was used to quantify the diagnostic accuracy of the two predictive models. RESULTS: Over a 16-month period, data on 1,360 patients were entered in a national database and analyzed. Peptic ulcer bleeding was recorded in 60.7% of cases. One or more comorbidities were present in 66% of patients. Endoscopic treatment was delivered in all high-risk patients followed by high-dose intravenous proton pump inhibitor in 95% of them. Sixty-six patients died (mortality 4.85%; 3.54-5.75). The PNED score showed a high discriminant capability and was significantly superior to the Rockall score in predicting the risk of death (AUC 0.81 (0.72-0.90) vs. 0.66 (0.60-0.72), P<0.000). Positive likelihood ratio for mortality in patients with a PNED risk score >8 was 16.05. CONCLUSIONS: The Italian 10-point score for the prediction of death was successfully validated in this independent population of patients with non-variceal gastrointestinal bleeding. The PNED score is accurate and superior to the Rockall score. Further external validation at the international level is needed.

Alpha- and beta-tubulin expression in rectal cancer development.

BACKGROUND: Microtubules are involved in cell growth and division, motility, signalling and in the development and maintenance of cell shape. Consequently, the non-equilibrium dynamics of these microtubules can be crucial to cellular function, including cancer development. Although the involvement of tubulins in human development has been well investigated, the role of alpha- and beta-tubulins in human tumorigenesis still remains controversial. The aim of this study was to investigate alpha- and beta-tubulin protein expression in rectal cancer development. PATIENTS AND METHODS: By immuno-histochemistry, using alpha- and beta-tubulin monoclonal antibodies, 66 patients were examined, 32 of whom (22 male, 10 female; range 31-60 years, mean age 49.5 years) had preneoplastic lesions discovered during endoscopic surveillance, which were classified as mild, moderate and severe dysplastic polyps of the rectum, and 34 had invasive adenocarcinomas (24 male, 10 female; range 39-60 years, mean 52 years) of the rectum, with no local or distant metastases at the time of surgical resection. RESULTS: In preneoplastic lesions, no statistically significant relationship was found among alpha- and beta-tubulin protein expression, grade of dysplasia, or other clinical data. Statistical association among alpha- and beta-tubulin immunoreactivity and Dukes' stages B and C was found with p = 0.017 and p = 0.009, respectively. No statistical relationship was found between alpha- and beta-tubulin protein expression among different grades of dysplasia. On the contrary, a significant relationship was detected among tubulins in different stages of cancer. CONCLUSION: In this preliminary study a significant difference of alpha- and beta-tubulin protein expressions was found in polyps and invasive cancer of the rectum, indicating a possible role of tubulins in invasive, but not in preinvasive cancer development. This preliminary data suggest the possibility of performing alpha- and beta-tubulin protein expression in order to identify B stage versus C stage rectal cancer, before surgical treatment.