Applying Lyon consensus criteria in the work-up of patients with extra-oesophageal symptoms - A multicentre retrospective study.

BACKGROUND: The diagnosis of gastro-oesophageal reflux disease (GERD) based on otolaryngologist's assessment of laryngoscopic findings remains contentious in terms of sensitivity and specificity. AIMS: To evaluate GERD prevalence, applying Lyon 2.0 Consensus criteria, in patients with extra-oesophageal symptoms undergoing laryngoscopic examination and impedance-pH monitoring. METHODS: In this retrospective assessment, we included 470 patients with extra-oesophageal symptoms, either isolated or combined with typical symptoms, who had been referred to six tertiary Italian Gastroenterology Units between January and December 2020. Of these, 274 underwent 24-h impedance-pH monitoring and laryngoscopy off PPI therapy. GERD diagnosis followed Lyon Consensus 2.0 criteria, incorporating mean nocturnal baseline impedance when pH-impedance monitoring was inconclusive. RESULTS: Laryngoscopic examination revealed pathological findings (predominantly posterior laryngitis) in 71.2% (195/274). GERD was diagnosed in 29.2% (80/274) via impedance-pH monitoring. The prevalence of GERD in patients with positive or negative laryngoscopy was similar (32.3% vs. 21.5%, p = 0.075). No significant difference in proximal reflux occurrences was noted between positive and negative laryngoscopy groups (33.3% vs. 24.1%, p = 0.133). Laryngoscopy demonstrated sensitivity and specificity of 78.8% and 32.0%, respectively, with a positive predictive value (PPV) of 32.3% and negative predictive value (NPV) of 28.4%. In contrast, a threshold of four concurrent laryngoscopic signs, identified in only eight patients, demonstrated a PPV of 93.8% and a NPV of 73.6% (sensitivity 25.4%, specificity 99.2%). CONCLUSION: This study underscores the limited diagnostic accuracy of laryngoscopy, emphasising the necessity of impedance-pH monitoring for confirming GERD diagnoses using Lyon 2.0 criteria in patients with suspected extra-oesophageal symptoms.

Alcohol consumption pattern and risk of Barrett's oesophagus and erosive oesophagitis: an Italian case-control study.

Knowledge about the association between alcohol and Barrett's oesophagus and reflux oesophagitis is conflicting. In this case-control study we evaluated the role of specific alcoholic beverages (red and white wine, beer and liquors) in 339 Barrett's oesophagus and 462 oesophagitis patients compared with 619 endoscopic controls with other disorders, recruited in twelve Italian endoscopic units. Data on alcohol and other individual characteristics were obtained from structured questionnaires. No clear, monotonic significant dose-response relationship was pointed out for red wine. However, a generalised U-shaped trend of Barrett's oesophagus/oesophagitis risk due to red wine consumption particularly among current drinkers was found. Similar results were also found for white wine. Liquor/spirit consumption seemed to bring about a 1·14-2·30 risk excess, although statistically non-significant, for current Barrett's oesophagus/oesophagitis drinkers. Statistically significant decreasing dose-response relationships were found in Barrett's oesophagus for frequency and duration of beer consumption. Similar, but less clear downward tendencies were also found for oesophagitis patients. In conclusion, although often not statistically significant, our data suggested a reduced risk of Barrett's oesophagus and oesophagitis with a low/moderate intake of wine and beer consumption. A non-significant increased risk of Barrett's oesophagus/oesophagitis was observed with a higher intake of any type of heavy alcohol consumption, but no conclusion can be drawn owing to the high number of non-spirit drinkers and to the small number of drinkers at higher alcohol intake levels.

Smoking as an independent determinant of Barrett's esophagus and, to a lesser degree, of reflux esophagitis.

PURPOSE: To evaluate the role of smoking in Barrett's esophagus (BE) and erosive esophagitis (E) compared to endoscopic controls with no BE or E. Smoking is considered a cause of both BE and E, but results on this topic are quite controversial. METHODS: Patients with BE (339), E (462) and controls (619: 280 with GERD (gastroesophageal reflux disease)-negative and 339 with GERD-positive anamnesis) were recruited in 12 Italian endoscopy units. Data were obtained from structured questionnaires. RESULTS: Among former smokers, a remarkable upward linear trend was found in BE for all smoking-related predictors. In particular, having smoked for more than 32 years increased the risk more than two times (OR 2.44, 95 % CL 1.33-4.45). When the analysis was performed in the subgroup of subjects with GERD-negative anamnesis, the risk of late quitters (<9 years) passed from OR 2.11 (95 % CL 1.19-3.72) to OR 4.42 (95 % CL 1.52-12.8). A noticeably positive dose-response relationship with duration was seen also among current smokers. As regards E, no straightforward evidence of association was detected, but for an increased risk of late quitters (OR 1.84, 95 % CL 1.14-2.98) in former smokers and for early age at starting (OR 3.63, 95 % CL 1.19-11.1) in GERD-negative current smokers. CONCLUSIONS: Smoking seems to be an independent determinant of BE and, to a lesser degree, of E. The elevation in risk is independent from GERD and is already present in light cigarette smokers. Smoking cessation may reduce, but not remove this risk.

A predictive model identifies patients most likely to have inadequate bowel preparation for colonoscopy.

BACKGROUND & AIMS: An inadequate level of bowel preparation can affect the efficacy and safety of colonoscopy. Although some factors have been associated with outcome, there is no strategy to identify patients at high risk for inadequate preparation. We searched for factors associated with an inadequate level of preparation and tested the validity of a predictive clinical rule based on these factors. METHODS: We performed a prospective study of 2811 consecutive patients who underwent colonoscopy examinations at 18 medical centers; clinical and demographic data were collected before the colonoscopy. Bowel preparation was classified as adequate or inadequate; 925 patients (33%) were found to have inadequate preparation. Multivariate analysis was used to identify factors associated with inadequate preparation, which were expressed as odds ratio (OR) and used to build a predictive model. RESULTS: Factors associated with inadequate bowel preparation included being overweight (OR, 1.5), male sex (OR, 1.2), a high body mass index (OR, 1.1), older age (OR, 1.01), previous colorectal surgery (OR, 1.6), cirrhosis (OR, 5), Parkinson disease (OR, 3.2), diabetes (OR, 1.8), and positive results in a fecal occult test (OR, 0.6). These factors predicted which patients would have inadequate cleansing with 60% sensitivity, 59% specificity, 41% positive predictive value, and 76% negative predictive value; they had an under the receiver operating characteristic curve value of 0.63. Assuming 100% efficacy of a hypothetical regimen to address patients predicted to be at risk of inadequate preparation, the rate would decrease from 33% to 13%. CONCLUSIONS: We identified factors associated with inadequate bowel preparation for colonoscopy and used these to build an accurate predictive model.

[GerdQ: tool for the diagnosis and management of gastroesophageal reflux disease in primary care]. / GerdQ: uno strumento per la diagnosi e la gestione della malattia da reflusso gastroesofageo nella medicina generale.

Diagnosis and effective management of gastroesophageal reflux (GERD) need a new approach. The 2009 Montreal Consensus recommended that the clinical diagnosis of GERD should be made on the presence of troublesome symptoms. GerdQ, a patient centered-self assessment questionnaire, is made to assist health care professionals. Also, it is easy to use, no diagnostic test required, for example without previous specialist referral or endoscopy. GerdQ is a well documented questionnaire, developed on the basis of evidence. GerdQ has three potential uses in clinical practice: (1) to diagnose gastroesophagel reflux disease with an accuracy similar to that of the gastroenterological evaluation; (2) to assess the relative impact of the disease on patient's lives and to assist in choice of treatment; (3) to measure response to treatment over the time.

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.

Improvement of metabolic syndrome following intragastric balloon: 1 year follow-up analysis.

OBJECTIVE: This study aimed to assess the impact of intragastric balloon (IGB)-induced body weight loss on metabolic syndrome in obese patients and evaluate what happens during 1-year follow-up. METHODS: To this end, data were collected on 143 obese patients (body mass index (BMI) 36.2+/-5.7 kg/m2) who underwent IGB insertion between January 2000 and December 2005. Outcomes were recorded at BioEnterics Intragastric Balloon removal time (t0) and at 6-month (t6) and 12-month (t12) follow-up. RESULTS: Significant BMI, excess body weight loss percentage, and body weight loss percentage (BWL%) were observed at t0 (29.6+/-4.6 kg/m2; 29.3+/-4.8%; 14.1+/-5.7%), followed by partial weight regain at t12 (32.4+/-4.3 kg/m2; 26.1+/-4.9%; 11.2+/-4.6%). Incidence of metabolic syndrome dropped from 34.8% (pre-IGB value) to 14.5% (t0) and 11.6% (t12). Likewise, type 2 diabetes mellitus (DM), hypertriglyceridemia, hypercholesterolemia, and blood hypertension (BH) incidence decreased from 32.6%, 37.7%, 33.4%, and 44.9% (pre-IGB values) to 20.9%, 14.5%, 16.7%, and 30.4% at t0 and 21.3%, 17.4%, 18.9%, and 34.8% at t12. HbA1c blood concentration shifted from an initial value of 7.5+/-2.1% to 5.7+/-1.9% (t0), 5.6+/-0.7% (t6), and 5.5+/-0.9% (t12). Patients suffering from DM or BH stopped or diminished relative drug consumption at t12. Negligible modifications were reported as regards HDL cholesterol and hyperuricemia. CONCLUSION: Weight regain is commonly observed during long-term follow-up after IGB removal. Nevertheless, the maintenance of at least 10% of the BWL%, as reported at 1-year follow-up, is associated with an improvement in metabolic syndrome.

HER-2 overexpression/amplification in Barrett's oesophagus predicts early transition from dysplasia to adenocarcinoma: a clinico-pathologic study.

Barrett's oesophagus (BO) is the primary precursor lesion for oesophageal adenocarcinoma (ADC). The natural history of metaplasia-dysplasia-carcinoma sequence remains largely unknown. HER2/neu oncogene results overexpressed/amplified in preneoplastic lesions and in ADC of the oesophagus and it has been associated with poor prognosis. Our aim was to evaluate the role of HER2 overexpression/amplification in predicting the conversion from precursor lesions to ADC. We retrospectively evaluated by univariate analysis of single variables clinical records and histological specimens of 21 patients with a confirmed diagnosis of BO and/or oesophageal dysplasia. Clinical variables included age, gender, alcohol and smoking intake, presence of symptoms (pyrosis, disphagia) and endoscopic features (length). HER2 status was studied by immunohistochemistry and fluorescence in situ hybridization (FISH) on paraffin-embedded tissue. The end-points were the occurrence of progression and the time-to-progression (TTP) from the initial histologic lesion to the worst pathological pattern. Median age at diagnosis was 63 years (range 37-84). BO median length was 4.5 cm. Progression occurred in 11 of 21 patients and median TTP was 24 months. HER2 was overexpressed/amplified in 8 of 21 (38%) patients. HER2 overexpression/ amplification and the presence of dysplasia were statistically associated with progression (P= 0.038). This study provides evidence for a possible role of HER2 in the transition from dysplasia to ADC of the oesophagus. This fact could help in identifying patients at high risk of malignant transformation.

Predictive factors of mortality from nonvariceal upper gastrointestinal hemorrhage: a multicenter study.

OBJECTIVES: From an Italian Registry of patients with upper gastrointestinal hemorrhage (UGIH), we assessed the clinical outcomes and explored the roles of clinical, endoscopic, and therapeutic factors on 30-day mortality in a real life setting. METHODS: Prospective analysis of consecutive patients endoscoped for UGIH at 23 community and tertiary care institutions from 2003 to 2004. Covariates and outcomes were defined a priori and 30-day follow-up obtained. Logistic regression analysis identified predictors of mortality. RESULTS: One thousand and twenty patients were included. A total of 46 patients died for an overall 4.5% mortality rate. In all, 85% of deaths were associated with one or more major comorbidity. Sixteen of 46 patients (35%) died within the first 24 h of the onset of bleeding. Of these, eight had been categorized as ASA class 1 or 2 and none of them was operated upon, despite a failure of endoscopic intention to treatment in four. Regression analysis showed advanced age, presence of severe comorbidity, low hemoglobin levels at presentation, and worsening health status as the only independent predictors of 30-day mortality (P < 0.001). The acute use of a PPI exerted a protective effect (OR 0.23, 95% CI 0.09-0.73). Recurrent bleeding was low (3.2%). Rebleeders accounted for only 11% of the total patients deceased (OR 3.27, 95% CI 1.5-11.2). CONCLUSIONS: These results indicate that 30-day mortality for nonvariceal bleeding is low. Deaths occurred predominantly in elderly patients with severe comorbidities or those with failure of endoscopic intention to treatment.

Fluorescence in situ hybridization to evaluate dysplasia in Barrett's esophagus: a pilot study.

BACKGROUND: Histological disagreement is frequent in the diagnosis and grading of dysplasia in Barrett's esophagus (BE). AIMS: To identify selective markers for dysplasia in BE and to improve the differentiation between low-grade dysplasia (LGD) and high-grade dysplasia (HGD). METHODS: Eight BE esophageal mucosectomies (7 males) were analyzed by conventional histology and immunohistochemistry for p53 and Fluorescence In situ Hybridization (FISH) for chromosomes X, Y, 4, 8, 17, 18. The female mucosectomy was considered as a control for the XY probe. RESULTS: p53 confirmed multifocal dysplasia in all cases. All patients displayed increased aneusomy for chromosomes 4, 8, 17 and 18 along the sequence of cancer progression. There was also a trend for chromosome 8 to be below the FISH cutoff; 50% of cases showed aneusomy for chromosome 18 in areas with differing grades of dysplasia. Aneusomy was increased for chromosomes 4 and 17, to a similar extent in LGD and HGD. In male specimens, the presence of chromosome Y was revealed in Barrett's mucosa and LGD, but not in HGD and intramucosal carcinoma. CONCLUSIONS: FISH in BE may be useful diagnostic to confirm the diagnosis of HGD. Loss of chromosome Y might be a selective marker of HGD in male patients.

[Giant intrathyroidal parathyroid cyst with hyperparathyroidism: a case report]. / Voluminosa cisti paratiroidea intratiroidea determinante iperparatiroidismo. Caso clinico.

Parathyroid cysts are rare lesions. A correct pre-operative diagnosis is rarely formulated. The Authors report a case of young woman with hyperparathyroidism do to a giant intrathyroidal parathyroid cyst. Aetiology, diagnosis and management are discussed.

Endoscopic mucosal resection for high-grade dysplasia and intramucosal carcinoma in Barrett's esophagus: an Italian experience.

AIM: To evaluate endoscopic mucosal resection (EMR) in patients with high-grade dysplasia (HGD) and/or intramucosal cancer (IMC) in Barrett's esophagus (BE). METHODS: Between June 2000 and December 2003, 39 consecutive patients with HGD (35) and/or IMC (4) underwent EMR. BE >30 mm was present in 27 patients. In three patients with short segment BE (25.0%), HGD was detected in a normal appearing BE. Lesions had a mean diameter of 14.8+/-10.3 mm. Mucosal resection was carried out using the cap method. RESULTS: The average size of resections was 19.7+/-9.4 x 14.6+/-8.2 mm. Histopathologic assessment post-resection revealed 5 low-grade dysplasia (LGD) (12.8%), 27 HGD (69.2%), 2 IMC (5.1%), and 5 SMC (-12.8%). EMR changed the pre-treatment diagnosis in 10 patients (25.6%). Three patients with SMC underwent surgery. Histology of the surgical specimen revealed 1 T0N0 and 2 T1N0 lesions. The remaining two patients were cancer free at 32.5 and 45.6 mo, respectively. A metachronous lesion was detected after 25 mo in one patient with HGD. Intra-procedural bleeding, controlled at endoscopy, occurred in four patients (10.3%). After a median follow-up of 34.9 mo, all patients remained in remission. CONCLUSION: In the medium term, EMR is effective and safe to treat HGD and/or IMC within BE and is a valuable staging method. It could become an alternative to surgery.

Oesophageal manometry in early and definite systemic sclerosis.

The objective of this study was to evaluate the oesophageal dysfunction in patients with "early" systemic sclerosis (SSc), as defined by LeRoy and Medsger, to compare it with that of patients with definite SSc, and to correlate it with other features of the disease. Oesophageal manometry results were retrospectively evaluated in 181 patients classified by the 2001 LeRoy and Medsger criteria and the 1980 American College of Rheumatology (ACR) criteria: group 1: limited SSc: Raynaud's phenomenon plus specific nailfold capillaroscopy abnormalities and/or autoantibodies; group 2: limited cutaneous SSc not satisfying the ACR criteria (lcSSc ACR-); group 3: lcSSc ACR+; group 4: diffuse cutaneous SSc. Peristaltic abnormalities in the oesophageal body were present in 73 of 125 patients with SSc ACR+ (groups 3 and 4) compared with 13 of 56 with SSc ACR- (groups 1 and 2) (p < 0.0001). They were more severe in patients with more advanced disease (1 vs 2; 1 vs 3; 1 vs 4; 2 vs 4; p < 0.05) and in patients anti-Scl-70+ than in patients anticentromere positive (p = 0.02). Abnormalities of the lower oesophageal sphincter (LES) were present in 35 of 125 patients with SSc ACR+ and 11 of 56 with SSc ACR- (not statistically different). They were correlated with forced vital capacity (FVC) (LES pressure: p = 0.0005; LES length: p = 0.0004). Abnormalities of the oesophageal body and of the LES were found in 21 and 16% of 46 patients without oesophageal symptoms. Oesophageal manometry can detect abnormalities in a sizeable proportion of patients with "early SSc" not fulfilling the ACR criteria, including asymptomatic patients. The correlation between LES abnormalities and FVC suggests a possible causal relationship between these disease manifestations.

Is esophageal pH monitoring used appropriately in an open-access system? A prospective multicenter study.

OBJECTIVES: To evaluate the referral patterns and indications for esophageal pH monitoring in an open-access system and to determine whether these indications conform to practice guidelines of the American Gastroenterological Association (AGA). METHODS: A total of 851 consecutive patients referred for ambulatory pH monitoring to nine open-access gastrointestinal units over a 12-month period received a structured interview. The indication for the examination was decided by the physician performing the procedure, on the basis of the patient's clinical history and main complaint. RESULTS: Three hundred and twenty-three (38%) examinations were for indications in accordance with the guidelines. The proportion of appropriate requests in each center ranged from 34% to 47%. This figure was not significantly different in larger gastrointestinal units (more than 150 examinations per year) and smaller ones (35% and 40%; p= 0.14). The proportion of appropriate requests was 45% for gastroenterologists, 38% for surgeons, 32% for other specialists, and 24% for primary care physicians (PCPs) (p < 0.001). The percentage of appropriateness was significantly different between gastrointestinal specialists and PCPs (p < 0.001 vs gastroenterologists, p= 0.015 vs GI surgeons), and between gastroenterologists and other specialists (p= 0.006). The underuse of an empirical trial of acid-suppression therapy in patients with suspected reflux disease and the overuse of this test to confirm a diagnosis in patients with erosive esophagitis and in endoscopy-negative cases with typical symptoms responding completely to antisecretory therapy accounted for most of the referrals, which was not in accordance with the guidelines. CONCLUSIONS: In an open-access system, a high proportion of esophageal pH studies are done for indications not consistent with published guidelines, particularly among the examinations not requested by gastrointestinal specialists. Further education is still needed on the appropriate use of esophageal pH monitoring and management of gastroesophageal reflux disease (GERD).