Unmet needs in Barret's esophagus diagnosis and treatment: a narrative review.

Background and Objective: This narrative review discusses Barrett's esophagus management in the context of perceived deficiencies or controversies. Barrett's adenocarcinoma incidence has not clearly been impacted by Barrett's screening and surveillance. Methods: The following report was derived from articles using PubMed and Google searches. The search was concentrated on Barrett's esophagus screening and management guidelines. Key Content and Findings: Comprehensive literature searches that highlight potential deficiencies or controversies regarding the current approach to Barrett's esophagus were employed. Esophageal adenocarcinoma incidence is rapidly increasing and this malignancy usually presents in an advanced and unresectable state. This is despite the significant expenditure of resources and time in endoscopic screening for and surveillance of Barrett's esophagus. Thus, more widespread screening for Barrett's esophagus may be considered. In addition, there are apparent inefficiencies and precision lack in the performance of endoscopic surveillance. This relates mainly to the lack of endoscopic cues for dysplasia. On the other hand, relatively low-risk subjects have frequent screening or surveillance procedures increasing cost. Lastly, endoscopic ablation for Barrett's with dysplasia has moderately good efficacy, especially for eradication of dysplasia, but mandates intensive post-therapy endoscopic surveillance. There is some concern for subsurface development of advanced Barrett's lesions. Fortunately, there is intense research in improving Barrett's esophagus diagnosis and treatment. Our narrative review will delineate deficiencies and potential measures to remedy them. Conclusions: In conclusion, screening for Barrett's esophagus and surveillance in Barrett's subjects have minimal established benefits, but proposed changes in screening practices and innovations in Barrett's esophagus endoscopic surveillance and dysplasia therapy have great promise.

The Impact of COVID-19 Infection on Miscellaneous Inflammatory Disorders of the Gastrointestinal Tract.

The novel coronavirus pandemic of COVID-19 has emerged as a highly significant recent threat to global health with about 600,000,000 known infections and more than 6,450,000 deaths worldwide since its emergence in late 2019. COVID-19 symptoms are predominantly respiratory, with mortality largely related to pulmonary manifestations, but the virus also potentially infects all parts of the gastrointestinal tract with related symptoms and manifestations that affect patient treatment and outcome. COVID-19 can directly infect the gastrointestinal tract because of the presence of widespread angiotensin-converting enzyme 2 receptors in the stomach and small intestine that can cause local COVID-19 infection and associated inflammation. This work reviews the pathopysiology, clinical manifestations, workup, and treatment of miscellaneous inflammatory disorders of the gastrointestinal tract other than inflammatory bowel disease.

Diarrhea and Coronavirus Disease 2019 Infection.

The global coronavirus disease-2019 (COVID-19) pandemic has caused significant morbidity and mortality, thoroughly affected daily living, and caused severe economic disruption throughout the world. Pulmonary symptoms predominate and account for most of the associated morbidity and mortality. However, extrapulmonary manifestations are common in COVID-19 infections, including gastrointestinal (GI) symptoms, such as diarrhea. Diarrhea affects approximately 10% to 20% of COVID-19 patients. Diarrhea can occasionally be the presenting and only COVID-19 symptom. Diarrhea in COVID-19 subjects is usually acute but is occasionally chronic. It is typically mild-to-moderate and nonbloody. It is usually much less clinically important than pulmonary or potential thrombotic disorders. Occasionally the diarrhea can be profuse and life-threatening. The entry receptor for COVID-19, angiotensin converting enzyme-2, is found throughout the GI tract, especially in the stomach and small intestine, which provides a pathophysiologic basis for local GI infection. COVID-19 virus has been documented in feces and in GI mucosa. Treatment of COVID-19 infection, especially antibiotic therapy, is a common culprit of the diarrhea, but secondary infections including bacteria, especially Clostridioides difficile, are sometimes implicated. Workup for diarrhea in hospitalized patients usually includes routine chemistries; basic metabolic panel; and a complete hemogram; sometimes stool studies, possibly including calprotectin or lactoferrin; and occasionally abdominal CT scan or colonoscopy. Treatment for the diarrhea is intravenous fluid infusion and electrolyte supplementation as necessary, and symptomatic antidiarrheal therapy, including Loperamide, kaolin-pectin, or possible alternatives. Superinfection with C difficile should be treated expeditiously. Diarrhea is prominent in post-COVID-19 (long COVID-19), and is occasionally noted after COVID-19 vaccination. The spectrum of diarrhea in COVID-19 patients is presently reviewed including the pathophysiology, clinical presentation, evaluation, and treatment.

Gastrointestinal Bleeding in COVID-19-Infected Patients.

COVID-19 infection is an ongoing catastrophic global pandemic with significant morbidity and mortality that affects most of the world population. Respiratory manifestations predominate and largely determine patient prognosis, but gastrointestinal (GI) manifestations also frequently contribute to patient morbidity and occasionally affect mortality. GI bleeding is usually noted after hospital admission and is often one aspect of this multisystem infectious disease. Although the theoretical risk of contracting COVID-19 from GI endoscopy performed on COVID-19-infected patients remains, the actual risk does not seem to be high. The introduction of PPE and widespread vaccination gradually increased the safety and frequency of performing GI endoscopy in COVID-19-infected patients. Three important aspects of GI bleeding in COVID-19-infected patients are (1) GI bleeding is often from mucosal erosions from mucosal infalammation that causes mild GI bleeding; (2) severe upper GI bleeding is often from PUD or stress gastritis from COVID-19 pneumonia; and (3) lower GI bleeding frequently arises from ischemic colitis associated with thromboses and hypercoagulopathy from COVID-19 infection. The literature concerning GI bleeding in COVID-19 patients is presently reviewed.

Peroral endoscopic myotomy for achalasia.

Peroral endoscopic myotomy (POEM) for achalasia (sometimes also referred as E-POEM to distinguish it from its offshoots such as G-POEM for gastroparesis or Z-POEM for Zenker's diverticula) is the newest treatment modality but has already been well validated as a standard intervention for esophageal achalasia. POEM was conceived as a natural orifice transluminal endoscopic surgery (NOTES) procedure with an incisionless, endoscopic approach to myotomy. It matches or exceeds the efficacy of its surgical counterpart, the laparoscopic Heller myotomy, with superiority for type III (spastic) achalasia. However, there are issues, especially regarding GERD after POEM that will likely result in further refinements of technique and post-procedural care. We will summarize the current status of POEM including description of technique variations and review of comparative data vis a vis Heller myotomy (HM) and pneumatic dilation (PD) and we will delve into some of the seminal issues around GERD assessment, management and prevention.

Solithromycin in Children and Adolescents With Community-acquired Bacterial Pneumonia.

BACKGROUND: Solithromycin is a new macrolide-ketolide antibiotic with potential effectiveness in pediatric community-acquired bacterial pneumonia (CABP). Our objective was to evaluate its safety and effectiveness in children with CABP. METHODS: This phase 2/3, randomized, open-label, active-control, multicenter study randomly assigned solithromycin (capsules, suspension or intravenous) or an appropriate comparator antibiotic in a 3:1 ratio (planned n = 400) to children 2 months to 17 years of age with CABP. Primary safety endpoints included treatment-emergent adverse events (AEs) and AE-related drug discontinuations. Secondary effectiveness endpoints included clinical improvement following treatment without additional antimicrobial therapy. RESULTS: Unrelated to safety, the sponsor stopped the trial prior to completion. Before discontinuation, 97 participants were randomly assigned to solithromycin (n = 73) or comparator (n = 24). There were 24 participants (34%, 95% CI, 23%-47%) with a treatment-emergent AE in the solithromycin group and 7 (29%, 95% CI, 13%-51%) in the comparator group. Infusion site pain and elevated liver enzymes were the most common related AEs with solithromycin. Study drug was discontinued due to AEs in 3 subjects (4.3%) in the solithromycin group and 1 (4.2%) in the comparator group. Forty participants (65%, 95% CI, 51%-76%) in the solithromycin group achieved clinical improvement on the last day of treatment versus 17 (81%, 95% CI, 58%-95%) in the comparator group. The proportion achieving clinical cure was 60% (95% CI, 47%-72%) and 68% (95% CI, 43%-87%) for the solithromycin and comparator groups, respectively. CONCLUSIONS: Intravenous and oral solithromycin were generally well-tolerated and associated with clinical improvement in the majority of participants treated for CABP.

POEM, GPOEM, and ZPOEM.

Our tripartite narrative review discusses Peroral Endoscopic Myotomy (POEM), gastric POEM (GPOEM) and POEM for Zenker's diverticula (ZPOEM). POEM is the prototypical procedure that launched the novel "3rd space endoscopy" field of advanced endoscopy. It revolutionized achalasia therapy by offering a much less invasive version of the prior gold standard, the laparoscopic Heller myotomy (HM). We review in detail indications, outcomes, technique variations and comparative data between POEM and HM particularly with regard to the hotly debated issue of GERD. We then proceed to discuss two less illustrious but nevertheless important offshoots of the iconic POEM procedure: GPOEM for gastroparesis and ZPOEM for the treatment of hypopharyngeal diverticula. For GPOEM, we discuss the rationale of pylorus-directed therapies, briefly touch on GPOEM technique variations and then focus on the importance of proper patient selection and emerging data in this area. On the third and final part of our review, we discuss ZPOEM and expound on technique variations including our "ultra-short tunnel technique". Our review emphasizes that, despite the superiority of endoscopy over surgery for the treatment of hypopharyngeal diverticula, there is no clear evidence yet of the superiority of the newfangled ZPOEM technique compared to the conventional endoscopic myotomy technique practiced for over two decades prior to the advent of ZPOEM.

Inflammatory bowel disease and pregnancy: fertility, complications and treatment.

Inflammatory bowel disease (IBD) is commonly diagnosed and treated in the young population. Therefore, it is common that women anticipating or undergoing pregnancy will have to cope with the additional burden of their IBD. Pregnancy in an IBD patient also presents challenges for the practitioner, in that the usual diagnostic and therapeutic armamentarium of potential tests and therapies is disrupted. This review covers the implications of IBD for fertility, pregnancy and offspring, and discusses the management of IBD in pregnancy.

Burgeoning study of sentinel-node analysis on management of early gastric cancer after endoscopic submucosal dissection.

Endoscopic submucosal dissection (ESD) represents an organ-preserving alternative to surgical resection of early gastric cancer. However, even with ESD yielding en-bloc resection specimens, there are concerns regarding tumor spread such as with larger lesions, ulcerated lesions, undifferentiated pathology and submucosal invasion. Sentinel node navigational surgery (SNNS) when combined with ESD offers a minimally invasive alternative to the traditional extended gastrectomy and lymphadenectomy if lack of lymph node spread can be confirmed. This would have a clear advantage in terms of potential complications and quality of life. However, SNNS, though useful in other malignancies such as breast cancer and melanoma, may not have a sufficient sensitivity for malignancy and negative predictive value in EGC to justify this as standard practice after ESD. The results of SNNS may improve with greater standardization and more involved dissection, technological innovations and more experience and validation such that the paradigm for post-ESD resection of EGC may change and include SNNS.

Learning Curve for Endoscopic Submucosal Dissection With an Untutored, Prevalence-Based Approach in the United States.

BACKGROUND & AIMS: Endoscopic submucosal dissection (ESD) is widely used in Asia to resect early-stage gastrointestinal neoplasms, but use of ESD in Western countries is limited. We collected data on the learning curve for ESD at a high-volume referral center in the United States to guide development of training programs in the Americas and Europe. METHODS: We performed a retrospective analysis of consecutive ESDs performed by a single operator at a high-volume referral center in the United States from 2009 through 2017. ESD was performed in 540 lesions: 449 mucosal (10% esophageal, 13% gastric, 5% duodenal, 62% colonic, and 10% rectal) and 91 submucosal. We estimated case volumes required to achieve accepted proficiency benchmarks (>90% for en bloc resection and >80% for histologic margin-negative (R0) resection) and resection speeds >9cm2/hr. RESULTS: Pathology analysis of mucosal lesions identified 95 carcinomas, 346 premalignant lesions, and 8 others; the rate of en bloc resection increased from 76% in block 1 (50 cases) to a plateau of 98% after block 5 (250 cases). The rate of R0 resection improved from 45% in block 1 to >80% after block 5 (250 cases) and ∼95% after block 8 (400 cases). Based on cumulative sum analysis, approximately 170, 150, and 280 ESDs are required to consistently achieve a resection speed >9cm2/hr in esophagus, stomach, and colon, respectively. CONCLUSIONS: In an analysis of ESDs performed at a large referral center in the United States, we found that an untutored, prevalence-based approach allowed operators to achieve all proficiency benchmarks after ∼250 cases. Compared with Asia, ESD requires more time to learn in the West, where the untutored, prevalence-based approach requires resection of challenging lesions, such as colon lesions and previously manipulated lesions, in early stages of training.

Updated Systematic Review of Achalasia, with a Focus on POEM Therapy.

AIM: To systematically review clinical presentation, diagnosis, and therapy of achalasia, focusing on recent developments in high-resolution esophageal manometry (HREM) for diagnosis and peroral endoscopic myotomy (POEM) for therapy. METHODS: Systematic review of achalasia using computerized literature search via PubMed and Ovid of articles published since 2005 with keywords ("achalasia") AND ("high resolution" or "HREM" or "peroral endoscopic myotomy" or "POEM"). Two authors independently performed literature searches and incorporated articles into this review by consensus according to prospectively determined criteria. RESULTS: Achalasia is an uncommon esophageal motility disorder, usually manifested by dysphagia to solids and liquids, and sometimes manifested by chest pain, regurgitation, and weight loss. Symptoms often suggest more common disorders, such as gastroesophageal reflux disease (GERD), thus often delaying diagnosis. Achalasia is a predominantly idiopathic chronic disease. Diagnosis is typically suggested by barium swallow showing esophageal dilation; absent distal esophageal peristalsis; smoothly tapered narrowing ("bird's beak") at esophagogastric junction; and delayed passage of contrast into stomach. Diagnostic findings at high-resolution esophageal manometry (HREM) include: distal esophageal aperistalsis and integrated relaxation pressure (trough LES pressure during 4 s) > 15 mmHg. Achalasia is classified by HREM into: type 1 classic; type 2 compartmentalized high pressure in esophageal body, and type 3 spastic. This classification impacts therapeutic decisions. Esophagogastroduodenoscopy is required before therapy to assess esophagus and esophagogastric junction and to exclude distal esophageal malignancy. POEM is a revolutionizing achalasia therapy. POEM creates a myotomy via interventional endoscopy. Numerous studies demonstrate that POEM produces comparable, if not superior, results compared to standard laparoscopic Heller myotomy (LHM), as determined by LES pressure, dysphagia frequency, Eckardt score, hospital length of stay, therapy durability, and incidence of GERD. Other therapies, including botulinum toxin injection and pneumatic dilation, have moderately less efficacy and much less durability than POEM. CONCLUSION: This comprehensive review suggests that POEM is equivalent or perhaps superior to LHM for achalasia in terms of cost efficiency, hospital length of stay, and relief of dysphagia, with comparable side effects. The data are, however, not conclusive due to sparse long-term follow-up and lack of randomized comparative clinical trials. POEM therapy is currently limited by a shortage of trained endoscopists.

Potential role of new technological innovations in nonvariceal hemorrhage.

The present armamentarium of endoscopic hemostatic therapy for non-variceal upper gastrointestinal hemorrhage includes injection, electrocautery and clips. There are newer endoscopic options such as hemostatic sprays, endoscopic suturing and modifications of current options including coagulation forceps and over-the-scope clips. Peptic hemorrhage is the most prevalent type of nonvariceal upper gastrointestinal hemorrhage and traditional endoscopic interventions have demonstrated significant hemostasis success. However, the hemostatic success rate is less for other entities such as Dieulafoy's lesions and bleeding from malignant lesions. Novel innovations such as endoscopic submucosal dissection and peroral endoscopic myotomy has spawned a need for dependable hemostasis. Gastric antral vascular ectasias are associated with chronic gastrointestinal bleeding and usually treated by standard argon plasma coagulation (APC), but newer modalities such as radiofrequency ablation, banding, cryotherapy and hybrid APC have been utilized as well. We will opine on whether the newer hemostatic modalities have generated success when traditional modalities fail and should any of these modalities be routinely available in the endoscopic toolbox.

Stricter national standards are required for credentialing of endoscopic-retrograde-cholangiopancreatography in the United States.

Endoscopic-retrograde-cholangiopancreatography (ERCP) is now a vital modality with primarily therapeutic and occasionally solely diagnostic utility for numerous biliary/pancreatic disorders. It has a significantly steeper learning curve than that for other standard gastrointestinal (GI) endoscopies, such as esophagogastroduodenoscopy or colonoscopy, due to greater technical difficulty and higher risk of complications. Yet, GI fellows have limited exposure to ERCP during standard-three-year-GI-fellowships because ERCP is much less frequently performed than esophagogastroduodenoscopy/colonoscopy. This led to adding an optional year of training in therapeutic endoscopy. Yet many graduates from standard three-year-fellowships without advanced training intensely pursue independent/unsupervised ERCP privileges despite inadequate numbers of performed ERCPs and unacceptably low rates of successful selective cannulation of desired (biliary or pancreatic) duct. Hospital credentialing committees have traditionally performed ERCP credentialing, but this practice has led to widespread flouting of recommended guidelines (e.g., planned privileging of applicant with 20% successful cannulation rate, or after performing only 7 ERCPs); and intense politicking of committee members by applicants, their practice groups, and potential competitors. Consequently, some gastroenterologists upon completing standard fellowships train and learn ERCP "on the job" during independent/unsupervised practice, which can result in bad outcomes: high rates of failed bile duct cannulation. This severe clinical problem is indicated by publication of ≥ 12 ERCP competency studies/guidelines during last 5 years. However, lack of mandatory, quantitative, ERCP credentialing criteria has permitted neglect of recommended guidelines. This work comprehensively reviews literature on ERCP credentialing; reviews rationales for proposed guidelines; reports problems with current system; and proposes novel criteria for competency. This work advocates for mandatory, national, written, minimum, quantitative, standards, including cognitive skills (possibly assessed by a nationwide examination), and technical skills, assessed by number performed (≥ 200-250 ERCPs), types of ERCPs, success rate (approximately ≥ 90% cannulation of desired duct), and letters of recommendation by program director/ERCP mentor. Mandatory criteria should ideally not be monitored by a hospital committee subjected to intense politicking by applicants, their employers, and sometimes even competitors, but an independent national entity, like the National Board of Medical Examiners/American Board of Internal Medicine.

Systematic review of safety and efficacy of therapeutic endoscopic-retrograde-cholangiopancreatography during pregnancy including studies of radiation-free therapeutic endoscopic-retrograde-cholangiopancreatography.

AIM: To systematically review safety/efficacy of therapeutic endoscopic-retrograde-cholangiopancreatography (ERCP) performed during pregnancy, considering fetal viability, fetal teratogenicity, premature delivery, and future postpartum development of the infant. METHODS: Systematic computerized literature search performed using PubMed with the key words "ERCP" and "pregnancy". Two clinicians independently reviewed the literature, and decided on which articles to incorporate in this review based on consensus and preassigned priorities. Large clinical trials, meta-analyses, systematic reviews, and controlled trials were assigned higher priority than review articles or small clinical series, and individual case reports were assigned lowest priority. Dr. Cappell has formal training and considerable experience in conducting systematic reviews, with 4 published systematic reviews in peer-reviewed journals indexed in PubMed during the last 2 years, and with a PhD in neurophysiology that involved 5 years of training and research in biomedical statistics. RESULTS: Advances in imaging modalities, including abdominal ultrasound, MRCP, and endoscopic ultrasound, have generally obviated the need for diagnostic ERCP in non-pregnant and pregnant patients. Clinical experience with performing ERCP during pregnancy is burgeoning, with > 500 cases of therapeutic ERCP reported in the literature, aside from a national registry study of 58 patients. These studies show that therapeutic ERCP has a very high rate of technical success in clearing the bile duct of gallstones, and has a relatively low and acceptable rate of maternal and fetal complications. The great majority of births after therapeutic ERCP are full-term, have normal birth weights, and are healthy. A recent trend is performing ERCP without radiation to eliminate radiation teratogenicity. Systematic literature review reveals 147 cases of ERCP without fluoroscopy in 8 clinical series. These studies demonstrate extremely high technical success in endoscopically removing choledocholithiasis, favorable maternal outcomes with rare maternal ERCP complications, and excellent fetal outcomes. ERCP without fluoroscopy generally confirms proper biliary cannulation by aspiration of yellow bile per sphincterotome or leakage of yellow bile around an inserted guide-wire. CONCLUSION: This systematic literature review reveals ERCP is relatively safe and efficacious during pregnancy, with relatively favorable maternal and fetal outcomes after ERCP. Recommendations are provided about ERCP indications, special ERCP techniques during pregnancy, and prospects for future research.

Introduction of endoscopic submucosal dissection in the West.

Endoscopic submucosal dissection (ESD) is well established in Asia as a modality for selected advanced lesions of both the upper and lower gastrointestinal tract, but ESD has not attained the same niche in the West due to a variety of reasons. These include competition from traditional surgery, minimally invasive surgery and endoscopic mucosal resection. Other obstacles to ESD introduction in the West include time commitment for learning and doing procedures, a steep learning curve, special equipment, lack of mentors, cost issues, interdisciplinary conflicts, concern regarding complications and lack of support from institutions and interfacing departments. There are intrinsic differences in pathology prevalence (e.g., early gastric cancer) between the two regions that are less conducive for ESD implementation in the West. We will elaborate on these issues and suggest measures as well as a protocol to overcome these obstacles and hopefully allow introduction of ESD as a tenable option for appropriate patients.

Spiral enteroscopy-assisted ERCP in bariatric-length Roux-en-Y anatomy: a large single-center series and review of the literature (with video).

BACKGROUND: Deep enteroscopy-assisted ERCP (DEA-ERCP) in post-bariatric Roux-en-Y (RY) anatomy is challenging. Laparoscopy-assisted ERCP (LA-ERCP) and EUS-directed transgastric ERCP (EDGE) are technically easier and faster but are more invasive and morbid procedures. Therefore, we have used DEA-ERCP as our first-line approach, reserving EDGE and LA-ERCP for cases in which adjunctive techniques that cannot be performed through an enteroscope are required (eg, EUS-FNA, sleeve sphincter of Oddi manometry), or DEA-ERCP failures. The 2 main methods for DEA-ERCP are balloon- and spirus-assisted. Current literature on spiral enteroscopy ERCP (SE-ERCP) in bariatric RY anatomy is scant with low success rates reported. Our center has nearly exclusively used SE-ERCP for bariatric patients. Here, we report one of the largest such series to date. METHODS: This is a retrospective cohort study of consecutive patients with bariatric-length RY anatomy who had SE-ERCP from December 2009 to October 2016 at a tertiary care center, by one operator (S.N.S.). Primary outcomes included success at reaching the papilla, cannulation success, success of desired therapeutic intervention, and overall SE-ERCP success. RESULTS: Thirty-five SE-ERCPs were performed (28 in bariatric RY gastric bypass and 7 other long-limb RY surgical reconstructions). The papilla was reached in 86% (30/35) of cases. Cannulation success in patients in whom deep cannulation was indicated (28/30) was 100% (28/28 cases, including the 24 cases with native papilla). Therapeutic ERCP success was 100% (28/28). Overall SE-ERCP success was 86% (30/35). Median length of stay was 3 days. Median procedure time was 189 minutes. Reasons for SE-ERCP failures included RY anastomosis stricture, adhesions (2), long Roux limb, and redundant small bowel. Two of these patients underwent interventional radiology-guided percutaneous biliary drainage, 2 patients had laparoscopy-assisted ERCP, and 1 patient had EUS-guided antegrade cholangioscopy with sphincteroplasty and stone clearance. There were no adverse events. CONCLUSION: With sufficient allotted time (median procedure time ∼3 hours) and high operator experience (a single-operator volume that exceeds that of other published series), SE-ERCP is safe and effective in bariatric, long-limb RY patients with an overall success rate of 86%, which is higher than previously reported.