Eosinophilic Esophagitis: Cytokines Expression and Fibrotic Markers in Comparison to Celiac Disease.

INTRODUCTION: Eosinophilic esophagitis (EoE) is now recognized as the main inflammatory condition that leads to fibrosis, unlike other chronic inflammatory gastrointestinal diseases, such as celiac disease. The aim of our study is to characterize the collagen deposition and cytokine expression involved in the fibrogenic response in patients affected by EoE in comparison to celiac disease. MATERIALS AND METHODS: Consecutive patients with a clinical suspicion of untreated EoE or active celiac disease were enrolled. In the control group, patients with negative upper endoscopy were included. Total RNA was isolated from biopsy specimens using a commercial kit (SV Total RNA Isolation System, Promega Italia Srl). Quantitative real-time PCR (qRT-PCR) was performed in triplicate using a StepOne™ Real-Time PCR instrument (Thermo Fisher Scientific, Monza, Italy). mRNA encoding for inflammatory molecules: interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin 13 (IL-13), and fibrotic markers: transforming growth factor beta 1 (TGF-ß), mitogen-activated protein kinase kinase kinase 7 (MAP3K7), serpin family E member 1 (SERPINE1), were quantified using TaqMan Gene Expression Assays (Applied Biosystems). RESULTS: In EoE, the qPCR analysis showed an increase in all the inflammatory cytokines. Both IL-5 and Il-3 mRNA expression resulted in a statistically significant increase in oesophageal mucosa with respect to the celiac duodenum, while no differences were present in IL-4 expression. TGF-ß expression was similar to the controls in the mid esophagus but reduced in the distal EoE esophagus (RQ: 0.46 ± 0.1). MAP3K7 expression was reduced in the mid esophagus (RQ: 0.59 ± 0.3) and increased in the distal esophagus (RQ: 1.75 ± 0.6). In turn, the expression of SERPINE1 was increased in both segments and was higher in the mid than in the distal esophagus (RQ: 5.25 ± 3.9, 1.92 ± 0.9, respectively). Collagen deposition was greater in the distal esophagus compared to the mid esophagus [18.1% ± 8 vs. 1.3% ± 1; p = 0.008]. CONCLUSIONS: The present study confirms the esophageal fibrotic involution involving the distal esophagus and shows that the inflammatory pathway in EoE is peculiar to this disease and different from other chronic inflammatory gastrointestinal disorders such as celiac disease.

Does Sleeve Gastrectomy Worsen Gastroesophageal Reflux Disease in Obese Patients? A Prospective Study.

BACKGROUND: To evaluate the impact of laparoscopic sleeve gastrectomy (LSG) and gastric bypass (LGB) on gastroesophageal reflux disease (GERD). METHODS: GERD was evaluated by the Modified Italian Gastroesophageal reflux disease-Health-Related Quality of Life (MI-GERD-HRQL) questionnaire, pH-manometry, endoscopy, and Rx-esophagogram, before and 12 months after surgery. Based on these exams, patients without GERD underwent LSG, and patients with GERD underwent LGB. RESULTS: Thirteen and six patients underwent LSG and LGB, respectively. After LSG, the only statistically significant difference observed at pH-manometry was the median DeMeester score, from 5.7 to 22.7 (P = .0026). De novo GERD occurred in 6 patients (46.2%), with erosive esophagitis in one. The median MI-GERD-HRQL score improved from 3 to 0. Overall, nine patients underwent LGB, but three were lost to follow-up. Preoperative pH-manometry changed the surgical indication from LSG to LGB in 7 out of 9 patients (77.8%). Six patients who underwent LGB completed the study, and at pH-manometry, statistically significant differences were observed in the percentage of total acid exposure time, with the number of reflux episodes lasting >5 minutes and DeMeester score (P = .009). The median MI-GERD-HRQL score improved from 6.5 to 0. Statistically significant differences were not observed at endoscopy and Rx-esophagogram findings in both groups. CONCLUSIONS: LSG has a negative impact on GERD, even in patients without preoperative GERD. LGB confirmed to be the intervention of choice in patients with GERD. Preoperative pH-manometry may identify patients with silent GERD, to candidate them to LGB rather than LSG. pH-manometry should be used more liberally to establish the correct surgical indication on objective grounds.

Manometric and pH-monitoring changes after laparoscopic sleeve gastrectomy: a systematic review.

PURPOSE: Aim of this systematic review is to assess the changes in esophageal motility and acid exposure of the esophagus through esophageal manometry and 24-hours pH-monitoring before and after laparoscopic sleeve gastrectomy (LSG). METHODS: Articles in which all patients included underwent manometry and/or 24-hours pH-metry or both, before and after LSG, were included. The search was carried out in the PubMed, Embase, Cochrane, and Web of Science databases, revealing overall 13,769 articles. Of these, 9702 were eliminated because they have been found more than once between the searches. Of the remaining 4067 articles, further 4030 were excluded after screening the title and abstract because they did not meet the inclusion criteria. Thirty-seven articles were fully analyzed, and of these, 21 further articles were excluded, finally including 16 articles. RESULTS: Fourteen and twelve studies reported manometric and pH-metric data from 402 and 547 patients, respectively. At manometry, a decrease of the lower esophageal sphincter resting pressure after surgery was observed in six articles. At 24-hours pH-metry, a worsening of the DeMeester score and/or of the acid exposure time was observed in nine articles and the de novo gastroesophageal reflux disease (GERD) rate that ranged between 17.8 and 69%. A meta-analysis was not performed due to the heterogeneity of data. CONCLUSIONS: After LSG a worsening of GERD evaluated by instrumental exams was observed such as high prevalence of de novo GERD. However, to understand the clinical impact of LSG and the burden of GERD over time further long-term studies are necessary.

Sleeve gastrectomy and gastroesophageal reflux: a comprehensive endoscopic and pH-manometric prospective study.

BACKGROUND: The impact of sleeve gastrectomy (SG) on gastroesophageal reflux disease (GERD) is still greatly debated. Most of the current evidence available is solely based on symptom evaluation or medication use, while a minority have implemented objective functional measurements. OBJECTIVE: To better comprehend the pathophysiological mechanisms involved in the genesis of GERD after SG. SETTING: University Hospital, Italy. METHODS: A total of 21 patients affected by morbid obesity and eligible for SG were prospectively enrolled in the present study. Patients were evaluated by means of endoscopy, high-resolution manometry (HRM), 24-hour pH monitoring, and the Gastroesophageal Reflux Disease Health-Related Quality of Life questionnaire. RESULTS: Follow-up was completed at least 1 year post operation (mean follow-up, 14.3 ± 2.1 mo) by 19 patients. Body mass index decreased from 41.2 ± .9 to 26.8 ± .8 kg/m2 (P < .001). Distal contractile integral significantly decreased from 2772.8 ± 399.9 mm Hg/s/cm to 2060.4 ± 338.9 mm Hg/s/cm (P = .01). The 24-hour pH monitoring showed an overall reduction tendency of acid reflux, although this was not statistically significant. All analyzed endoscopic findings withstood substantial pejorative modifications after SG (P < .01). Distal contractile integral values at baseline predicted postoperative Z-line upward migration; HRM, distal latency, and DeMeester score at baseline predicted the development of erosive esophagitis at follow-up, by bootstrap estimates of a logistic regression. CONCLUSIONS: Postoperative GERD-related esophageal sequelae should be carefully considered after SG. Our results demonstrate how acid reflux does not seem to play a relevant role in the pathophysiology of post-SG GERD. Baseline HRM can help stratify the risk of developing erosive esophagitis and Z-line upward migration after SG, while postoperative endoscopic surveillance should be encouraged regardless of the presence or absence of symptoms.

Effects of Laparoscopic Sleeve Gastrectomy on Quality of Life Related to Gastroesophageal Reflux Disease.

Purpose: Effects of laparoscopic sleeve gastrectomy (LSG) on gastroesophageal reflux disease (GERD) symptoms are controversial. Our aim is to evaluate the effects of LSG on GERD symptoms in obese patients using a validated quality-of-life questionnaire. Methods: Records of 100 patients (median body mass index [BMI] 44.4 kg/m2, range 35-63.6) without hiatal hernia or severe GERD were analyzed. GERD symptoms were evaluated by GERD Health-Related Quality-of-Life (HRQL) questionnaire before and after surgery. Weight loss and comorbidity resolution were recorded. Results: Median GERD-HRQL scores decreased from 7 (range 0-44) to 3 (0-34) (P = .025) (median follow-up 56 months [range 7-136]). GERD-HRQL scores improved in 55 patients and worsened in 21; de novo GERD was observed in 10; no change occurred in 14 patients (differences being statistically significant: P = <.0001). On multilinear regression analysis, total preoperative GERD-HRQL score and postoperative BMI were independent variables for overall postoperative GERD-HRQL score: higher total preoperative GERD-HRQL score was associated with improved postoperative GERD-HRQL scores, whereas higher postoperative BMI was associated with worse total postoperative GERD-HRQL score. Resolution of diabetes, hypertension, and sleep apnea syndrome occurred in 84.4%, 68%, and 89.7% of patients, respectively. Conclusions: In obese patients, although LSG was associated with statistically significantly improved postoperative GERD-HRQL scores at mid-term follow-up in 55% of patients, only preoperative GERD-HRQL score and postoperative BMI were independent predictors of GERD after LSG. Higher overall preoperative GERD-HRQL score was associated with improved postoperative GERD-HRQL score. However, further research is needed to assess how to predict GERD outcome.

The central role of psychopathology and its association with disease severity in inflammatory bowel disease and irritable bowel syndrome.

BACKGROUND: Biopsychosocial models for both organic and functional gastrointestinal (GI) disorders can be found in the literature. To clarify the role of psychopathological factors and their relationship with GI symptom severity, several studies have examined them in inflammatory bowel disease (IBD) - occasionally distinguishing between ulcerative colitis (UC) and Crohn's disease (CD) - and in irritable bowel syndrome (IBS), leading to unclear results. AIMS: We aimed to evaluate the psychopathological features of IBD and IBS patients in comparison with healthy individuals and assess the association with disease severity. MATERIALS AND METHODS: Sixty-nine IBD outpatients, of which 35 UC and 34 CD, and 75 IBS ones were consecutively recruited at the third level Gastroenterological Center of our University Hospital; 76 healthy controls were also recruited. The psychological status was assessed with the Symptom Checklist-90-Revised (SCL-90-R). RESULTS: IBD and IBS patients showed significantly higher scores on the SCL-90-R Global Severity Index (GSI) and subscales than controls (all p-values<0.001), and IBS patients showed significantly higher GSI, depression, and anxiety scores than IBD patients (all p-values<0.01). Psychopathology was comparable between UC and CD patients. In IBD and IBS patients the SCL-90-R GSI was significantly associated with disease severity (p<0.001). CONCLUSIONS: The presence of chronic bowel symptoms, either organic or functional, is linked to a greater severity of psychopathology compared to the general population, possibly as a consequence of higher loads of stress due to the symptoms affecting everyday life. In both IBD and IBS patients, greater disease severity and worse psychopathological functioning are related.

Opioid-induced bowel dysfunction: suggestions from a multidisciplinary expert Board.

Constipation, one of the adverse effects of opioid therapy with a major impact on quality of life, is still an unmet need for cancer patients, particularly those with an advanced and progressive disease, and for non-cancer patients chronically treated with opioids. The awareness of this condition is poor among healthcare providers, despite the recent publication of guidelines and consensus conferences. An early multidisciplinary approach of opioid-induced bowel dysfunction (OIBD), based on available therapies of proven effectiveness, could support clinicians in managing this condition, thus increasing patients' adherence to pain therapy. Several Italian experts involved in the management of patients suffering from pain (anaesthesia pain therapy, oncology, haematology, palliative care, gastroenterology) joined in a Board in order to draw up an expert opinion on OIBD. The most frequent and still unsolved issues in this field were examined, including a more comprehensive definition of OIBD, the benefits of early intervention to prevent its occurrence and the most appropriate use of peripherally acting mu-opioid receptor antagonists (PAMORAs). The use of the recently introduced PAMORA naloxegol was analysed, in light of the current literature. The Board proposed a solution for each open issue in the form of recommendations, integrated with the contribution of representatives from different disciplines and often accompanied by procedural algorithms immediately usable and applicable in daily clinical practice. Safety and quality of life of the patient suffering from pain and from the adverse effects of pain therapies have been the mainstays of this expert opinion, in cooperation with general practitioners and caregivers.

A risk score system to timely manage treatment in Crohn's disease: a cohort study.

BACKGROUND: Clinical severity and intestinal lesions of Crohn's disease (CD) usually progress over time and require a step up adjustment of the therapy either to prevent or to treat complications. The aim of the study was to  develop a simple risk scoring system to assess in individual CD patients the risk of disease progression and the need for more intensive treatment and monitoring. METHODS: Prospective cohort study (January 2002-September 2014) including 160 CD patients (93 female, median age 31 years; disease behavior (B)1 25%, B2 55.6%, B3 19.4%; location (L)1 61%, L3 31.9%, L2 6%; L4 0.6%; perianal disease 28.8%) seen at 6-12-month interval. Median follow-up 7.9 years (IQR: 4.3-10.5 years). Poisson models were used to evaluate predictors, at each clinical assessment, of having the following outcomes at the subsequent clinical assessment a) use of steroids; b) start of azathioprine; c) start of anti-TNF-α drugs; d) need of surgery. For each outcome 32 variables, including demographic and clinical characteristics of patients and assessment of CD intestinal lesions and complications, were evaluated as potential predictors. The predictors included in the model were chosen by a backward selection. Risk scores were calculated taking for each predictor the integer part of the Poisson model parameter. RESULTS: Considering 1464 clinical assessments 12 independent risk factors were identified, CD lesions, age at diagnosis < 40 years, stricturing behavior (B2), specific intestinal symptoms, female gender, BMI < 21, CDAI> 50, presence of inflammatory markers, no previous surgery or presence of termino-terminal anastomosis, current use of corticosteroid, no corticosteroid at first flare-up. Six of these predicted steroids use (score 0-9), three to start azathioprine (score 0-4); three to start anti-TNF-α drugs (score 0-4); six need of surgery (score 0-11). The predicted percentage risk to be treated with surgery within one year since the referral assessment varied from 1 to 28%; with azathioprine from 3 to 13%; with anti-TNF-α drugs from 2 to 15%. CONCLUSIONS: These scores may provide a useful clinical tool for clinicians in the prognostic assessment and treatment adjustment of Crohn's disease in any individual patient.

Hiatoplasty with Crura Buttressing versus Hiatoplasty Alone during Laparoscopic Sleeve Gastrectomy.

INTRODUCTION: In obese patients with hiatal hernia (HH), laparoscopic sleeve gastrectomy (LSG) with cruroplasty is an option but use of prosthetic mesh crura reinforcement is debated. The aim was to compare the results of hiatal closure with or without mesh buttressing during LSG. METHODS: Gastroesophageal reflux disease (GERD) was assessed by the Health-Related Quality of Life (GERD-HRQL) questionnaire before and after surgery in two consecutive series of patients with esophageal hiatus ≤ 4 cm2. After LSG, patients in group A (12) underwent simple cruroplasty, whereas in group B patients (17), absorbable mesh crura buttressing was added. RESULTS: At mean follow-up of 33.2 and 18.1 months for groups A and B, respectively (p = 0.006), the mean preoperative GERD-HRQL scores of 16.5 and 17.7 (p = 0.837) postoperatively became 9.5 and 2.4 (p = 0.071). In group A, there was no difference between pre- and postoperative scores (p = 0.279), whereas in group B, a highly significant difference was observed (p = 0.002). The difference (Δ) comparing pre- and postoperative mean scores between the two groups was significantly in favor of mesh placement (p = 0.0058). CONCLUSIONS: In obese patients with HH and mild-moderate GERD, reflux symptoms are significantly improved at medium term follow-up after cruroplasty with versus without crura buttressing during LSG.

Simple versus reinforced cruroplasty in patients submitted to concomitant laparoscopic sleeve gastrectomy: prospective evaluation in a bariatric center of excellence.

BACKGROUND: Crural closure in addition to laparoscopic sleeve gastrectomy (LSG) represents a valuable option for the synchronous management of morbid obesity and hiatal defects, providing good outcomes in terms of weight loss and gastroesophageal reflux disease (GERD) symptoms control. The aim of this prospective study was to evaluate the safety and effectiveness of the reinforced cruroplasty during LSG compared with a concurrent group of simple cruroplasty. METHODS: The study groups included 96 morbidly obese patients who underwent simultaneous LSG and cruroplasty. Group A: 48 patients with hiatal areal defect <4 cm(2) and normal pillars (simple posterior cruroplasty); group B: 48 patients with hiatal areal defect >4 and <8 cm(2) with weakness of the right pillar (on-lay synthetic absorbable mesh-reinforced cruroplasty). Upper GI symptoms were assessed by Roma III standard questionnaire. Endoscopy, imaging, esophageal 24-h pH monitoring and HR manometry were performed in cases of persistent or recurrent symptoms after surgery. RESULTS: Mortality rate was nil. The conversion rate to open was 1 %. Intra-operative diagnosis of hiatal hernia occured in 41 patients (42.7 %). Mesh-related complications were none. Perioperative complications occurred in four patients (4.1 %). After 19- to 21-month follow-up, GERD symptom remission occurred in 89 % of patients. GERD symptoms were detected postoperatively in eight patients: six in group A (five symptomatic and radiological recurrences and one persistent) and two in group B (one persistent and one de novo GERD) (P < 0.05). CONCLUSIONS: The synthetic absorbable mesh offers an effective option for crural repair during LSG with no clinical recurrences at 19 months. The midterm results of this prospective comparative study evaluating two different technical options for cruroplasty confirm that the simultaneous procedures are safe and cruroplasty is effective in mild-to-moderate GERD control .

The effect of parathyroidectomy on chronic constipation in patients affected by primary hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is usually associated with chronic constipation; however, its prevalence is not defined by standardized criteria. The aim of the study was to evaluate both the prevalence of chronic constipation, defined by the standardized Rome diagnostic criteria III (Rome III) in PHPT, and the effect of parathyroidectomy (PTx). Fifty postmenopausal PHPT patients and 50 sex- and age-matched controls were studied. Each patient underwent mineral metabolism biochemical evaluation and completed a questionnaire and a 2-week diary card about bowel habits. PHPT patients were reevaluated after 6 months. According to Rome III, 40 % of PHPT patients had chronic constipation compared with 12 % of controls (p = 0.0002). The only difference between constipated PHPT patients (group A, n = 20) and those without constipation (group B, n = 30) was higher mean PTH values (79.9 ± 18.7 ng/l vs. 65.4 ± 26.0 ng/l; p = 0.03), which predicted the presence of constipation (p = 0.004, OR 1.059, CI 1.011-1.059). Forty percent of PHPT patients had undergone PTx. In group A, constipation was resolved in 80 % of patients after PTx compared to none of the same group who had not undergone PTx (p = 0.0007). In group B, 17.6 % of patients who had not undergone PTx became, after 6 months, constipated. According to Rome III, a higher prevalence of chronic constipation in PHPT patients was observed compared with controls. PTH levels predicted constipation. A significant reduction of chronic constipation was reported following successful surgery.

Morphologically and immunohistochemically undifferentiated gastric neoplasia in a patient with multiple metastatic malignant melanomas: a case report.

INTRODUCTION: Malignant melanoma is a neoplasia which frequently involves the gastrointestinal tract (GIT). GIT metastases are difficult to diagnose because they often recur many years after treatment of the primary cutaneous lesion and also manifest clinically at an advanced stage of the neoplasia. Furthermore, GIT metastases can appear in various morphological forms, and therefore immunohistochemistry is often useful in distinguishing between a malignant melanoma and other malignancies. CASE PRESENTATION: We report the case of a 60-year-old man with a multiple metastatic melanoma who underwent an upper endoscopy to clarify the possible involvement of the gastric wall with a mass localized in the upper abdomen involving the pancreas and various lymph nodes, which was previously described with computed tomography. Clinically, the patient reported a progressive loss of appetite, nausea and vomiting. The upper endoscopy and histological examination revealed a gastric location of an undifferentiated neoplasm with an absence of immunohistochemical characteristics referable to the skin malignant melanoma that was removed previously. CONCLUSION: The present case report shows the difficulty in diagnosing a metastatic melanoma in the GIT and therefore, it seems worthwhile to consider metastatic malignant melanoma in the differential diagnosis of undifferentiated neoplasia.