Factors influencing the presence of potentially explosive gases during colonoscopy: Results of the SATISFACTION study.

This study tested the hypothesis that bowel preparation with mannitol should not affect the colonic concentration of H2 and CH4 . Therefore, the SATISFACTION study, an international, multicenter, randomized, parallel-group phase II-III study investigated this issue. The phase II dose-finding part of the study evaluated H2 , CH4 , and O2 concentrations in 179 patients randomized to treatment with 50 g, 100 g, or 150 g mannitol. Phase III of the study compared the presence of intestinal gases in 680 patients randomized (1:1) to receive mannitol 100 g in single dose or a standard split-dose 2 L polyethylene glycol (PEG)-Asc preparation (2 L PEG-Asc). Phase II results showed that mannitol did not influence the concentration of intestinal gases. During phase III, no patient in either group had H2 or CH4 concentrations above the critical thresholds. In patients with H2 and/or CH4 levels above detectable concentrations, the mean values were below the risk thresholds by at least one order of magnitude. The results also highlighted the effectiveness of standard washing and insufflation maneuvers in removing residual intestinal gases. In conclusion, bowel cleansing with mannitol was safe as the concentrations of H2 and CH4 were the same as those found in patients prepared with 2 L PEG-Asc. In both groups, the concentrations of gases were influenced more by the degree of cleansing achieved and the insufflation and washing maneuvers performed than by the preparation used for bowel cleansing. The trial protocol was registered with ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT04759885) and with EudraCT (eudract_number: 2019-002856-18).

Epstein-Barr Virus (EBV) acute acalculous cholecystitis in an immunocompromised adult patient: a case report and a literature review of a neglected clinical presentation.

Primary Epstein-Barr virus (EBV) infection may present with self-limiting abdominal involvement, characterized by hepatitis with mild elevation of aminotransferases, splenomegaly, and rarely with acute acalculous cholecystitis (AAC). Usually, treatment of EBV related AAC is symptomatic, without the need for surgery. Here, we describe a severe case of AAC occurring as the first manifestation of infectious mononucleosis in a young adult woman, receiving treatment with interleukin 6 receptor (IL-6r) inhibitor for rheumatoid arthritis (RA); moreover, we have performed a review of the literature on EBV-related AAC.

Posterior Reversible Encephalopathy Syndrome After Azathioprine Administration in Severe Ulcerative Colitis.

Posterior reversible encephalopathy syndrome is a rare syndrome characterized by brain edema and neurological symptoms, often resulting from several drugs. Treatment is based on discontinuation, and diagnosis is thus essential. Only 13 cases of posterior reversible encephalopathy syndrome have been reported in inflammatory bowel diseases, and we present the first after azathioprine in adults. A 56-year-old patient with active ulcerative colitis was found unconscious 5 days after the institution of azathioprine. Right-sided hemiplegia was found after the patient regained consciousness. Magnetic resonance imaging showed altered signal associated with diffusion restriction in the occipital lobe and cerebral vasogenic edema. Complete regression of neurological signs occurred after azathioprine discontinuation.

Role of Ulcerative Colitis Endoscopic Index of Severity (UCEIS) versus Mayo Endoscopic Subscore (MES) in Predicting Patients' Response to Biological Therapy and the Need for Colectomy.

BACKGROUND: The main goal in the treatment of ulcerative colitis (UC) is to achieve mucosal healing. Despite being unvalidated, the most widely used scoring system is the Mayo endoscopic subscore (MES). However, the recently established and validated Ulcerative Colitis Endoscopic Index of Severity (UCEIS) represents an interesting alternative method in assessing endoscopic disease activity. OBJECTIVE: Due to a lack of reliable prognostic factors, the aim of this study was to investigate the diagnostic accuracy of the UCEIS and the MES, in predicting response to biological therapy and the need for colectomy. METHODS: We conducted a retrospective, uncontrolled, single-center study on UC patients with endoscopically active disease even with concomitant conventional and/or biological therapy, who had already started or had been changed a biological treatment. RESULTS: Sixty-one UC patients were enrolled. At baseline, 71% were naive to biological therapies and 41% had an extensive colitis. At control time (median time of 11.5 months), MES and UCEIS scores significantly decreased from those at baseline (from 2.6 to 1.8 and 5 to 3.2, respectively, p < 0.001). UCEIS, but not MES, was found to be significantly associated with unresponsiveness to therapy (p = 0.040). Moreover, when UCEIS was ≥7, all patients underwent colectomy after a median time of 5 months (p < 0.001). CONCLUSION: UCEIS may be superior to MES because of its accuracy and predictive role. Therefore, UCEIS should be considered for use in daily clinical practice.

Sonographic Differential Diagnosis in Deep Infiltrating Endometriosis: The Bowel.

Up to one-third of fertile-age women with severe endometriosis suffer from colonic involvement. Transvaginal ultrasonography has become a first-line diagnostic tool for the study of the pelvis and more specifically for the diagnosis of pelvic endometriosis. Accuracy of pelvic ultrasound for deep endometriosis increases with operator experience, but the difficulties in the differential diagnosis with diseases that can afflict the bowel tract remain a challenge. We reviewed noteworthy cases referred for secondary level diagnosis suspected of bowel endometriosis in which the subsequent ultrasound led to an alternative diagnosis. This case series aims to highlight awareness for both experts and less-experienced operators the possible differential diagnoses of bowel lesions that initially resemble endometriosis.

Gut microbiota and cancer: How gut microbiota modulates activity, efficacy and toxicity of antitumoral therapy.

Gut microbiota is involved in gastrointestinal carcinogenesis. Also, it modulates the activity, efficacy and toxicity of several chemotherapy agents, such as gemcitabine, cyclophosphamide, irinotecan, cisplatin and 5-Fluorouracil, and target therapy, such as tyrosine kinase inhibitors. More recently, accumulating data suggest that the composition of gut microbiota may also affect efficacy and toxicity of cancer immunotherapy. Therefore, the manipulation of gut microbiota through antibiotics, probiotics, prebiotics or fecal transplantation has been investigating with the aim to improve efficacy and mitigate toxicity of anticancer drugs.

Colorectal Anastomotic Stenosis: Lessons Learned after 1643 Colorectal Resections for Deep Infiltrating Endometriosis.

STUDY OBJECTIVE: To evaluate the incidence, risk factors, and treatment of colorectal anastomotic stenosis in patients who undergo rectosigmoid resection for deep infiltrating endometriosis (DIE). DESIGN: Retrospective analysis of a prospective database (Canadian Task Force classification III). SETTING: Public medical center. PATIENTS: All women who underwent laparoscopic rectosigmoid resections for DIE at our hospital between January 2002 and December 2016. INTERVENTION: All patients were evaluated clinically and endoscopically at 1 month and 3 months after bowel resection. Stenosis was defined as a lack of passage through the anastomosis of a 12-mm proctoscope. Symptomatic stenosis was defined as the presence of endoscopically confirmed stricture accompanied by at least 2 of the following symptoms: constipation, need to push, tenesmus, and ribbon stools. Only patients with symptomatic stenosis were studied. Demographic data, surgical techniques, and postoperative complications were recorded prospectively. Treatments and outcomes of anastomotic symptomatic strictures were analyzed. MEASUREMENTS AND MAIN RESULTS: A total of 1643 patients underwent laparoscopic rectosigmoid resection at our hospital between January 2002 and December 2016. Among these, 104 patients (6.3%) presented with symptomatic anastomotic stenosis. The median patient age was 27 years (range, 23-44 years), and the median interval between diagnosis and the onset of symptomatic stenosis was 57 days (range, 21-64 days). The only statistically significant predictors of anastomotic stenosis were the presence of ileostomy (p = .01) and previous pelvic surgery (p = .002). Treatment of choice was always conservative. Of the 104 patients in the study cohort, 90 (86.5%) underwent 3 endoscopic dilatations. No patient required reoperation. CONCLUSION: The anastomotic stricture is a recognized complication in patients following intestinal resection for DIE, and protective ileostomy is the sole modifiable factor related to anastomotic stenosis. Endoscopic dilatation is a valid option to treat this complication.

En Bloc Endoscopic Resection of Large Pedunculated Brunner's Gland Hamartoma: A Case Report.

Brunner's gland hamartoma (BGH) is an uncommon benign tumor arising from alkaline-based mucin-secreting glands of the duodenum. These lesions are typically discovered incidentally during upper gastrointestinal endoscopy or radiological diagnostics, even though they can eventually lead (in the case of increasing size) to obstructive or hemorrhagic symptoms. We report the case of a 67-year-old Caucasian man with two episodes of melena and epigastric pain during the last month. Esophagogastroduodenoscopy revealed a large pedunculated and eroded polyp inside the antrum with a 2-cm-long stalk arising from the anterior wall of the duodenal bulb. Endoscopic ultrasonography showed a submucosal lesion with homogeneous hyperechoic parietal thickening and some central gaps. The muscularis was undamaged. No lymphadenopathy was observed. We performed an en bloc endoscopic resection of the polyp. The size of the whole piece was approximately 6 × 3 × 2 cm, pseudocapsulated and tough in consistency. In the case presented, the en bloc endoscopic removal was successful despite the size of the tumor.

Bronchial reacutization and gastroesophageal reflux: is there a potential clinical correlation?

BACKGROUND: Pepsin plays a role in gastroesophageal reflux (GER). Aims of this study were to verify if pepsin could be the cause of frequent bronchial exacerbations and to check if the persistence of chronic respiratory symptoms were correlated with pre-existing respiratory diseases. METHODS: From January to May 2016, 42 patients underwent a diagnostic bronchoscopy. All patients had a history of at least one bronchial exacerbation during the previous year. Bronchial lavage fluid specimens were obtained. A semiquantitative assessment of pepsin in the samples was carried out based on the intensity of the test sample. RESULTS: Pepsin was present in 37 patients (88%), but in patients with bronchial asthma and chronic obstructive pulmonary disease (COPD), the finding of pepsin in the bronchoalveolar fluid was 100%. There was a strong positive statistical correlation between pepsin detection and radiological signs of GER (ρ=0.662), and between pepsin detection and diagnosis (ρ=0.682). No correlation was found between the bacteriology and the presence of pepsin in the airways (ρ=0.006). CONCLUSIONS: The presence of pepsin in the airways shows the occurrence of reflux. The persistence of respiratory symptoms by at least 2 months suggest an endoscopic bronchial examination. This straightforward test confirms the cause possible irritation of the airways and may prevent further diagnostic tests, such as an EGD or pH monitoring esophageal.

A germline predictive signature of response to platinum chemotherapy in esophageal cancer.

Platinum-based neoadjuvant therapy is the standard treatment for esophageal cancer (EC). At present, no reliable response markers exist, and patient therapeutic outcome is variable and very often unpredictable. The aim of this study was to understand the contribution of host constitutive DNA polymorphisms in discriminating between responder and nonresponder patients. DNA collected from 120 EC patients treated with platinum-based neoadjuvant chemotherapy was analyzed using drug metabolism enzymes and transporters (DMET) array platform that interrogates polymorphisms in 225 genes of drug metabolism and disposition. Four gene variants of DNA repair machinery, 2 in ERCC1 (rs11615; rs3212986), and 2 in XPD (rs1799793; rs13181) were also studied. Association analysis was performed with pTest software and corrected by permutation test. Predictive models of response were created using the receiver-operating characteristics curve approach and adjusted by the bootstrap procedure. Sixteen single nucleotide polymorphisms (SNPs) of the DMET array resulted significantly associated with either good or poor response; no association was found for the 4 variants mapping in DNA repair genes. The predictive power of 5 DMET SNPs mapping in ABCC2, ABCC3, CYP2A6, PPARG, and SLC7A8 genes was greater than that of clinical factors alone (area under the curve [AUC] = 0.74 vs 0.62). Interestingly, their combination with the clinical variables significantly increased the predictivity of the model (AUC = 0.78 vs 0.62, P = 0.0016). In conclusion, we identified a genetic signature of response to platinum-based neoadjuvant chemotherapy in EC patients. Our results also disclose the potential benefit of combining genetic and clinical variables for personalized EC management.

Italian consensus guidelines for the diagnostic work-up and follow-up of cystic pancreatic neoplasms.

This report contains clinically oriented guidelines for the diagnostic work-up and follow-up of cystic pancreatic neoplasms in patients fit for treatment. The statements were elaborated by working groups of experts by searching and analysing the literature, and then underwent a consensus process using a modified Delphi procedure. The statements report recommendations regarding the most appropriate use and timing of various imaging techniques and of endoscopic ultrasound, the role of circulating and intracystic markers and the pathologic evaluation for the diagnosis and follow-up of cystic pancreatic neoplasms.

The role of K-ras gene mutation analysis in EUS-guided FNA cytology specimens for the differential diagnosis of pancreatic solid masses: a meta-analysis of prospective studies.

BACKGROUND: Differential diagnosis of pancreatic solid masses with EUS-guided FNA (EUS-FNA) is still challenging in about 15% of cases. Mutation of the K-ras gene is present in over 75% of pancreatic adenocarcinomas (PADC). OBJECTIVE: To assess the accuracy of K-ras gene mutation analysis for diagnosing PADC. DESIGN: We systematically searched the electronic databases for relevant studies published. Data from selected studies underwent meta-analysis by use of a bivariate model providing a pooled value for sensitivity, specificity, diagnostic odds ratio, and summary receiver operating characteristic curve. SETTING: Meta-analysis of 8 prospective studies. PATIENTS: Total of 931 patients undergoing EUS-FNA for diagnosis of pancreatic solid masses. INTERVENTION: K-ras mutation analysis. MAIN OUTCOME MEASUREMENTS: Diagnostic accuracy of K-ras mutation analysis and of combined diagnostic strategy by using EUS-FNA and K-ras mutation analysis in the diagnosis of PADC. RESULTS: The pooled sensitivity of EUS-FNA for the differential diagnosis of PADC was 80.6%, and the specificity was 97%. Estimated sensitivity and specificity were 76.8% and 93.3% for K-ras gene analysis, respectively, and 88.7% and 92% for combined EUS-FNA plus K-ras mutation analysis. Overall, K-ras mutation testing applied to cases that were inconclusive by EUS-FNA reduced the false-negative rate by 55.6%, with a false-positive rate of 10.7%. Not repeating EUS-FNA in cases in which mutation testing of the K-ras gene is inconclusive would reduce the repeat-biopsy rate from 12.5% to 6.8%. LIMITATIONS: Small number of studies and between-study heterogeneity. CONCLUSION: K-ras mutation analysis can be useful in the diagnostic work-up of pancreatic masses, in particular when tissue obtained by EUS-FNA is insufficient, and the diagnosis inconclusive.

Interobserver agreement in contrast harmonic endoscopic ultrasound.

BACKGROUND AND AIM: Contrast harmonic endoscopic ultrasound (CH-EUS) was recently introduced to clinical practice; its reproducibility among endosonographers is unknown. Our aim was to assess the interobserver agreement (IA) in CH-EUS. METHODS: Fifteen endosonographers (eight experienced and seven non-experienced) from 11 Italian EUS centers evaluated 80 video-cases (40 solid pancreatic lesions, 20 pancreatic cystic lesions and 20 submucosal lesions) of CH-EUS, according to the degree of enhancement, the pattern of distribution and the washout of the contrast agent. IA within each group and between the two groups of observers was assessed with the Fleiss kappa statistic. RESULTS: Overall IA was moderate for the uptake and fair for the pattern of distribution and the washout. In solid pancreatic lesions, IA was moderate for the uptake and fair for the pattern and the washout. In cystic pancreatic lesions, IA was uniformly moderate for the assessment of uptake, slight for the pattern and fair for the washout. In submucosal tumors, IA was substantial for the uptake, slight for the pattern and fair for the washout. Non-experienced endosonographers demonstrated, in most cases, comparable IA with the experienced ones. CONCLUSIONS: Interobserver agreement among endosonographers for CH EUS was satisfactory. In particular, overall IA varied from slight to substantial, being fair in the majority of cases. Inherent structural features of the lesions, as well as technical differences between the variables assessed, could have accounted for the fluctuation of the results. Outcomes of IA were reproducible between experienced and non-experienced endosonographers.

Quality of life in patients with esophageal stenting for the palliation of malignant dysphagia.

Incidence of esophageal cancer (EC) is rising more rapidly in the Western world than that of any other cancer. Despite advances in therapy, more than 50% of patients have incurable disease at the time of presentation. This precludes curative treatment and makes palliative treatment a more realistic option for most of these patients. Dysphagia is the predominant symptom in more than 70% of patients with EC and although several management options have been developed in recent years to palliate this symptom, the optimum management is not established. Self-expanding metal stents (SEMS) are a well-established palliation modality for dysphagia in such patients. Health-related quality of life (HRQoL) is becoming a major issue in the evaluation of any therapeutic or palliative intervention. To date, only a few published studies can be found on Medline examining HRQoL in patients with advanced EC treated with SEMS implantation. The aim of this study was to review the impact on HRQoL of SEMS implantation as palliative treatment in patients with EC. All Medline articles regarding HRQoL in patients with advanced EC, particularly those related to SEMS, were reviewed. In most studies, relief of dysphagia was the only aspect of HRQoL being measured and SEMS implantation was compared with other palliative treatments such as brachytherapy and laser therapy. SEMS insertion provides a swift palliation of dysphagia compared to brachytherapy and no evidence was found to suggest that stent implantation is different to laser treatment in terms of improving dysphagia, recurrent dysphagia and better HRQoL, although SEMS insertion has a better technical success rate and also reduces the number of repeat interventions.

Role of Confocal Laser Endomicroscopy in Detection of Residual Barrett's Esophagus after Radiofrequency Ablation.

Endoscopic endoluminal radiofrequency ablation (RFA) is a novel and promising modality for Barrett's esophagus (BE) treatment. Actually the only surveillance method after the ablation treatment is random biopsies throughout the whole treated area. Confocal laser endomicroscopy (CLE) is a new endoscopic imaging tool that permits high-resolution microscopic examination of the gastrointestinal tract. The technology has garnered increasing attention because of its ability to provide real-time "optical" biopsy specimens, with a very high sensitivity and specificity. This paper summarize the potential application of CLE in the surveillance of the reepithelialization of BE, after endoscopic RFA.

Programmed cell death 4 (PDCD4) expression during multistep Barrett's carcinogenesis.

AIM: To test the contribution of programmed cell death 4 (PDCD4) tumour suppressor gene in Barrett's carcinogenesis. METHODS: PDCD4 immunohistochemical expression was assessed in 88 biopsy samples obtained from histologically proven long-segment Barrett's mucosa (BM; 25 non-intestinal columnar metaplasia, 25 intestinal metaplasia (IM), 16 low-grade intraepithelial neoplasia (LG-IEN), 12 high-grade IEN (HG-IEN) and 10 Barrett's adenocarcinoma (BAc)). As controls, 25 additional samples of native oesophageal mucosa (N) were obtained from patients with dyspepsia. To further support the data, the expression levels of miR-21, an important PDCD4 expression regulator, in 14 N, 5 HG-IEN and 11 BAc samples were determined by quantitative real-time PCR analysis. Results PDCD4 immunostaining decreased progressively and significantly with the progression of the phenotypic changes occurring during Barrett's carcinogenesis (p<0.001). Normal basal squamous epithelial layers featured strong PDCD4 nuclear immunoreaction (mostly coexisting with weak-moderate cytoplasmic staining). Non-intestinal columnar metaplasia and intestinal metaplasia preserved a strong nuclear immunostaining; conversely, a significant decrease in PDCD4 nuclear expression was seen in dysplastic (LG-IEN and HG-IEN) and neoplastic lesions. Weak-moderate cytoplasmic immunostaining was evident in cases of LG-IEN, while HG-IEN and BAc samples showed weak cytoplasmic or no protein expression. As expected, miR-21 expression was significantly upregulated in HG-IEN and BAc samples, consistently with PDCD4 dysregulation. CONCLUSIONS: These data support a significant role for PDCD4 downregulation in the progression of BM to BAc, and confirm miR-21 as a negative regulator of PDCD4 in vivo. Further efforts are needed to validate PDCD4 as a potential prognostic marker in patients with Barrett's oesophagus.

Gastrointestinal stromal tumors: report of an audit and review of the literature.

Gastrointestinal stromal tumors (GISTs), tumors characterized by c-KIT mutations, are the most frequent mesenchymal tumors of the digestive tract. The stomach is the most commonly involved site. Localization, size and mitotic rate are reliable predictors of survival and the two milestones of GISTs treatment are surgery and imatinib. This article is aimed to report the data of an audit, carried out on the morphological and clinical aspects of the disease and to review the present knowledge on GISTs. A total of 172 patients with GISTs (M : F=1 : 1; mean age 65 years) were recruited. The stomach was the most frequently involved site. In 50% of the cases the tumor was smaller than 5 cm, whereas major symptoms were observed in 43% of the cases. Predictors of progressive disease were present only in a small percentage of cases but the disease was in the metastatic phase in over 25% of the cases at diagnosis. Familial aggregation was rare but a consistent share of the patients (21%) had other synchronous or metachronous cancers. The most frequent mutations were in-frame deletions and point mutations of c-KIT exon 11. This report confirms in part the available data on GIST in a consecutive series of patients recruited in Italy and shows that only large collaborative multicenter studies provide data sound enough to enable making reasonable clinical and therapeutic choices, and suggests that, as a measure of secondary prevention, a diagnostic definition should be obtained in all submucosal lesions of the GI tract and that GIST patients should be screened for second tumors.

Endoscopic ultrasound: accuracy in staging superficial carcinomas of the esophagus.

BACKGROUND: Endoscopic procedures may represent an alternative to esophagectomy for superficial neoplasms of the esophagus (T1m/T1sm), but they are considered curative only in case of no lymph node involvement. Endoscopic ultrasound (EUS) is the most accurate method to define both T and N staging of esophageal carcinoma. Aims of the study were to assess the staging accuracy of EUS in superficial lesions (T1m and T1sm) of patients who were candidates for esophagectomy or local endoscopic resection and to establish which variables (site of neoplasm, histologic type, macroscopic appearance) can affect the accuracy of EUS in distinguishing between T1m and T1sm lesions. METHODS: The study population consisted of 55 patients with superficial carcinoma of the esophagus who underwent EUS (October 2002 to January 2007). Endoscopic ultrasound features were compared with findings from surgical specimens or samples obtained at mucosectomy. RESULTS: There were 33 patients with adenocarcinoma (60%), which developed on Barrett's esophagus in 27 cases, 21 patients (38%) with squamous cell carcinoma, and 1 (2%) with lymphoepithelial-like carcinoma. All lesions were confirmed as T1 on pathology. Of the 22 (40%) T1m lesions on EUS, 19 (86%) were confirmed as T1m on pathology; of the 33 T1sm on EUS, 22 (66%) were confirmed as T1sm. Positive predictive value of EUS for invasion of the submucosa was 67%, negative predictive value 86%, sensitivity 88%, specificity 63%, and diagnostic accuracy 75%. The accuracy of EUS in evaluating lymph node metastases was 71%, with a negative predictive value of 84%. Endoscopic ultrasound accuracy in differentiating mucosal from submucosal lesions increased from the lower esophagus or gastroesophageal junction to the mid and upper esophagus (71%, 76%, and 100%, respectively; not significant). As for the histologic type, accuracy was 70% for adenocarcinoma and 81% for squamous cell carcinoma, (not significant); for lesions detected as type 0-IIa (13 patients), accuracy was 100%; for type 0-I lesions (23 patients), accuracy was 70% (p = 0.03). CONCLUSIONS: Despite difficulties in differentiating mucosal from submucosal lesions, even with 20-MHz miniprobes, EUS remains an extremely valuable tool when nonsurgical treatments are considered. Its staging accuracy depends on site and macroscopic appearance of the neoplasm.