Definition, Pathogenesis, and Management of That Cursed Dyspepsia.

Dyspepsia is an umbrella term used to encompass a number of symptoms thought to originate from the upper gastrointestinal tract. These symptoms are relatively nonspecific; not surprisingly, therefore, a myriad of conditions may present with any one or a combination of these symptoms. Therein lays the clinician's first challenge: detecting the minority who may have a potentially life-threatening disorder, such as gastric cancer, from a population whose symptoms are, for the most part, considered functional in origin. The second challenge lies in the definition and management of those individuals with functional dyspepsia (FD); the major focus of this review. The Rome process has addressed the issue of FD definition and a look back at the evolution of Rome criteria for this disorder illustrates the complexities that have so frustrated us. There has been no shortage of hypotheses to explain symptom pathogenesis in FD; initially focused on gastric sensorimotor dysfunction, these have now strayed well into the duodenum and have come to entertain such factors as immune responses and the microbiome. FD has proven to be an equally challenging area for therapeutics; while the staple approaches of acid suppression and eradication of Helicobacter pylori have some limited efficacy in select populations, strategies to ameliorate symptoms in the majority of sufferers based on presumed pathophysiology have largely foundered. Lacking a validated biomarker(s) FD continues to be an elusive target and is likely to remain so until we can better define the various phenotypes that it must surely contain.

Topical steroids in eosinophilic esophagitis: Systematic review and meta-analysis of placebo-controlled randomized clinical trials.

BACKGROUND AND AIMS: Eosinophilic esophagitis (EoE) is a clinicopathologic condition characterized by symptoms of esophageal dysfunction in the presence of eosinophil-predominant inflammation of esophageal mucosa. Topical steroids are recommended as first line pharmacologic therapy in EoE. We aimed to determine the efficacy of topical steroids in inducing histologic and clinical remission in children and adults with EoE. METHODS: We performed a systematic search of the MEDLINE, EMBASE, Scopus, and Cochrane library databases for studies investigating the efficacy of topical steroids in EoE. We collected data on the number of patients, dose and duration of therapy, complete and partial histological response, and clinical improvement. We performed meta-analysis of placebo-controlled randomized clinical trials using Review Manager version 5.2. We used funnel plots to evaluate for publication bias. RESULTS: Five studies that included 174 patients with EoE were included in the meta-analysis. Topical fluticasone was administered in three studies involving 114 patients, and topical budesonide in two studies involving 60 patients. Patients treated with topical steroids, as compared with placebo, had higher complete histological remission (odds ratio [OR] 20.81, 95% confidence interval [CI] 7.03, 61.63) and partial histological remission (OR 32.20, 95% CI 6.82, 152.04). There was a trend towards improvement in clinical symptoms with topical steroids as compared with placebo but it did not reach statistical significance (OR 2.72, 95 %CI 0.90, 8.23). CONCLUSIONS: Topical corticosteroids seem to be effective in inducing histological remission but may not have similar significant impact in improving clinical symptoms of EoE. Studies with large sample size are needed to uniformly validate symptom improvement in EoE.

The use of combination biological or small molecule therapy in inflammatory bowel disease: A retrospective cohort study.

OBJECTIVE: There are limited data on using more than one biologic or small molecule drug combined to treat patients with inflammatory bowel disease. The aim of our study was to determine the effectiveness and safety of combination biologic use in inflammatory bowel disease. METHODS: We identified patients with Crohn's disease or ulcerative colitis who received treatment with a combination of two biologics or a biologic and a small molecule drug from 2015 to 2019 for persistent disease activity or concomitant rheumatological or dermatological disease. The primary end-point was effectiveness, based on improvements in inflammatory markers, clinical, and endoscopic remission. The secondary end-point was safety. RESULTS: Of the 50 patients treated with combination therapy there were significantly more patients in clinical and endoscopic remission at follow-up compared to baseline (50% vs 14%, P = 0.0018, delta 36%, 95% confidence interval [CI] 0.13-0.53; and 34% vs 6%, P = 0.0039, delta 28%, 95% CI 0.09-0.47), respectively. Median erythrocyte sedimentation rate (17 mm/h vs 13 mm/h, P = 0.002) and C-reactive protein (5.00 mg/dL vs 2.35 mg/dL, P = 0.002) also decreased posttreatment. There were eight serious adverse events and no deaths CONCLUSIONS: Combination biologic therapy appears to be an effective option for patients with refractory inflammatory bowel disease or concomitant autoimmune disease that is inadequately controlled by biologic monotherapy. There was an increased risk of serious infection compared with biologic monotherapy; however, this risk might be minimized by discontinuing immunomodulators prior to initiating combination therapy. Large prospective studies are needed to confirm these findings.

EUS and EUS-guided FNA/core biopsies in the evaluation of subepithelial lesions of the lower gastrointestinal tract: 10-year experience.

BACKGROUND AND OBJECTIVE: The widespread use of colonoscopy has led to an increasing number of subepithelial lesions (SELs) being detected in the lower gastrointestinal (GI) tract. This study aimed to analyze the utility of EUS and its role in the management of lower GI SELs. PATIENTS AND METHODS: Records of all patients who were referred for lower EUS evaluation of a SEL at a tertiary center between 2007 and 2018 were retrospectively reviewed after IRB approval. Data collection included patient/lesion characteristics, technical details of procedure, and pathology results. RESULTS: A total of 47 patients underwent EUS examinations for the evaluation of 49 suspected SEL in the lower GI tract (2 patients had 2 SELs each). Out of the 49 suspected lesions, the most frequent location was in the rectum (30/49, 61.2%). EUS showed extraluminal compression in 2 cases (2/49, 4.1%) and intraluminal lesions were identified in 40 cases (40/49, 81.6%). In 7 patients (7/49, 14.3%), no lesion could be identified by EUS. Twenty (20/49, 40.8%) SELs were malignant or had malignant potential. Twenty-six EUS-guided fine-needle aspirations (FNAs) and 14 EUS-core biopsies were performed. EUS-FNA alone was able to correctly diagnose 15/26 (57.7%) of the lower SELs. When EUS-guided fine needle biopsies (FNB) were performed during the same procedure, the final diagnosis was confirmed in 21/26 (80.8%) cases. There was only one procedure-related complication caused by use of narcotics. CONCLUSION: EUS-guided FNA/FNB are feasible and safe techniques for assessing lower GI SELs and provide valuable information regarding lesion characteristics and their malignant potential with high diagnostic accuracy.

Efficacy of Nasobiliary Tubes and Biliary Stents in Management of Patients with Bile Leak after Liver Transplantation: A Systematic Review.

BACKGROUND/AIMS: Bile leak is one of the most common complications of liver transplantation. The treatment options for bile leaks include conservative management, surgical re-intervention, percutaneous drainage and endoscopic drainage. We aimed to perform a systematic review to identify the efficacy of endoscopic treatment in the resolution of post-transplant bile leaks. METHODS: Two independent reviewers performed systematic literature search in PubMed, ISI Web of Science, grey literature and relevant references in May 2017. Human studies in English with documented post-liver transplant bile leaks were included. RESULTS: Thirty-four studies were included in the final analysis. The pooled efficacy of biliary stents for the resolution of post-transplant bile leaks was 82.43% compared with 87.15% efficacy of nasobiliary tubes. The efficacy of biliary stents was lower for anastomotic leaks (69.23%) compared to T-tube (90.9%) or cut-surface/ cystic duct stump related leaks (92.8%). Similarly, the efficacy of nasobiliary tube was also lower for anastomotic leaks (58.33%) compared to T-tube or cut-surface related leaks (100%). CONCLUSION: In this systematic review, the overall efficacy was 82.43% in biliary stent group, and 87.15% in nasobiliary tube group. Both biliary stent and nasobiliary tube were more effective in managing non-anastomotic leaks compared to anastomotic leaks.

The role of ferric carboxymaltose in the treatment of iron deficiency anemia in patients with gastrointestinal disease.

Iron deficiency anemia (IDA) is the most common form of nutritional anemia worldwide. Iron plays a pivotal role in vital functioning of almost every organ system. IDA affects both physical and psychological functioning of humans. Oral iron is considered as first-line therapy for the treatment of IDA due to low cost, good safety profile and ease of administration. However, the absorption of oral iron is affected by several factors and incidence of gastrointestinal side effects can lead to lack of adherence to therapy as well as poor efficacy. This has led to the emergence of intravenous iron therapy which is clearly superior to oral iron with higher increment of hemoglobin levels and rapid replenishment of iron stores. Ferric carboxymaltose (FCM) is a novel non-dextran intravenous iron form which has been approved for use in patients with iron deficiency who have had inadequate response to oral iron therapy, intolerance to oral iron, or nondialysis-dependent chronic kidney disease. The safety and efficacy of using FCM for the treatment of IDA has been demonstrated in several clinical trials. One dose can provide a large amount of iron and has a very short infusion time. It should be considered as first-line therapy in patients with active inflammation like inflammatory bowel disease when gastrointestinal absorption of oral iron may be compromised. It should also be given to patients who have inadequate response to oral iron therapy. It has been shown to be noninferior to other intravenous iron formulations with a good safety profile and produced fewer anaphylactic reactions.

Diagnosis of cystic lymphangioma of the colon by endoscopic ultrasound: Biopsy is not needed!

Cystic lymphangioma of the colon (CLC) is a rare benign lesion that is usually asymptomatic and found incidentally during colonoscopy. Limitations in the conventional noninvasive diagnostic techniques have led to surgical resection of these lesions for diagnostic confirmation. Classic endoscopic ultrasound (EUS) findings of colonic cystic lymphangioma are submucosal anechoic cystic spaces with septations, intact muscularis propria, and no solid component. Patients who are asymptomatic with lesions having classic appearance as cystic lymphangioma with EUS can be observed without any intervention. We herein report a case of cystic lymphangioma of distal transverse colon in an asymptomatic patient diagnosed noninvasively using 20-MHz miniprobe EUS and managed conservatively without any surgical intervention.

The role of endoscopic ultrasound in pancreatic cancer screening.

Pancreatic cancer (PC) is a highly lethal cancer. Despite a significant advancement in cancer treatment, the mortality rate of PC is nearly identical to the incidence rates. Early detection of tumor or its precursor lesions with dysplasia may be the most effective approach to improve survival. Screening strategies should include identification of the population at high risk of developing PC, and an intense application of screening tools with adequate sensitivity to detect PC at an early curable stage. Endoscopic ultrasound (EUS) and magnetic resonance imaging (MRI) seem to be the most promising modalities for PC screening based on the data so far. EUS had an additional advantage over MRI by being able to obtain tissue sample during the same examination. Several questions remain unanswered at this time regarding the age to begin screening, frequency of screening, management of asymptomatic pancreatic lesions detected on screening, timing of resection, and extent of surgery and impact of screening on survival. Novel techniques such as needle-based confocal laser endomicroscopy (nCLE), along with biomarkers, may be helpful to identify pancreatic lesions with more aggressive malignant potential. Further studies will hopefully lead to the development of strategies combining EUS with other technological/biological advancements that will be cost-effective and have an impact on survival.

EUS-Guided Needle-Based Confocal Laser Endomicroscopy: A Novel Technique With Emerging Applications.

Endoscopic ultrasound (EUS) has emerged as an excellent tool for imaging the gastrointestinal tract, as well as surrounding structures. EUS-guided fine-needle aspiration (EUS-FNA) has become the standard of care for the tissue sampling of a variety of masses and lymph nodes within and around the gut, providing further diagnostic and staging information. Confocal laser endomicroscopy (CLE) is a novel endoscopic method that enables imaging at a subcellular level of resolution during endoscopy, allowing up to 1000-fold magnification of tissue and providing an optical biopsy. A new procedure that has been developed in the past few years is needle-based confocal laser endomicroscopy (nCLE), which involves a mini-CLE probe that can be passed through a 1 9-gauge needle during EUS-FNA. This enables the real-time visualization of tissue at a microscopic level, with the potential to further improve the diagnostic accuracy of EUS-FNA. The device has been studied in animals as well as in humans, and the results so far have been promising. Recently, this method has also been used for the visualization of regulatory proteins and receptors in the pancreas, setting a cornerstone for nCLE in molecular imaging. The aim of this article is to review the role of EUS-guided nCLE in modern endoscopy and its implications in molecular imaging.

Role of endoscopic ultrasound in diagnosis and management of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is an aggressive tumor and a leading cause of cancer-related deaths globally. The mortality rate remains high despite many advances in treatment. HCC is frequently diagnosed late in its course due to lack of classical symptoms at earlier stages. Endoscopic ultrasound (EUS) has emerged as an important diagnostic tool for the diagnostic evaluation, staging, and treatment of gastrointestinal tract disorders. EUS-guided fine needle aspiration has been a valuable addition to EUS by being able to obtain tissue under direct visualization. Here, we review the potential role of EUS in the diagnosis and management of HCC. EUS seems to be a safe and reliable alternative method for obtaining tissue for diagnosis of liver cancer, especially for lesions that are inaccessible by traditional methods. EUS could play an important role in the diagnosis and management of HCC.

Utility of confocal laser endomicroscopy in identifying high-grade dysplasia and adenocarcinoma in Barrett's esophagus: a systematic review and meta-analysis.

Confocal laser endomicroscopy (CLE) is a novel endoscopic technique that has emerged as an important tool in the in-vivo visualization and detailed assessment of the mucosal layer and subcellular structures in Barrett's esophagus. Current guidelines recommend four-quadrant random biopsies for identification of high-grade dysplasia (HGD) in Barrett's esophagus. However, random biopsies are associated with sampling error and inconsistent histopathologic interpretation. CLE, by providing targeted biopsies, could decrease the sampling error and increase the yield of detection of HGD/adenocarcinoma [esophageal adenocarcinoma (EAC)]. We carried out a meta-analysis to evaluate the diagnostic accuracy of the CLE-based targeted biopsies in detecting HGD/adenocarcinoma compared with four-quadrant random biopsies. A search using medical subject headings (MeSH) terms and keywords was performed in the MEDLINE and Cochrane review databases and relevant studies were identified. All the studies that compared the diagnostic yield from CLE-based targeted biopsies to detect HGD/adenocarcinoma with a gold standard of histopathology were included and a meta-analysis was carried out to estimate the pooled sensitivity, specificity, and positive and negative likelihood ratios using Meta-Disc software. There were a total of seven studies with 345 patients and 3080 lesions that were finally included in the meta-analysis. All the studies had reported per-lesion analyses; however, only four of the seven studies had data reported on per-patient analyses. 'Per-lesion' analysis for the diagnosis of HGD/adenocarcinoma yielded a pooled sensitivity and specificity of 68% [95% confidence interval (CI) of 64-73%] and 88% (95% CI of 87-89%), respectively. The pooled positive and negative likelihood ratios were 6.56 (95% CI of 3.61-11.90) and 0.24 (95% CI of 0.09-0.63), respectively. Similar numbers were calculated on the basis of 'per-patient' basis, which showed a pooled sensitivity and specificity of 86% (95% CI of 74-96%) and 83% (95% CI of 77-88%), respectively. The pooled positive and negative likelihood ratios were 5.61 (95% CI of 2.00-15.69) and 0.21 (95% CI of 0.08-0.59), respectively. CLE, by providing targeted biopsies, has a good diagnostic accuracy in identifying HGD/EAC; however, the overall prevalence of HGD/EAC in the studies included was much higher than what would be seen in clinical practice and these results should be interpreted with caution. Because of its relatively low sensitivity and negative predictive value, CLE may currently not replace standard biopsy techniques for the diagnosis of HGD/EAC in Barrett's esophagus.