Esophageal anatomy and physiology vary across spastic and non-spastic phenotypes of disorders of esophagogastric junction outflow.

BACKGROUND: Pathophysiologic mechanisms of disorders of esophagogastric junction (EGJ) outflow are poorly understood. We aimed to compare anatomic and physiologic characteristics among patients with disorders of EGJ outflow and normal motility. METHODS: We retrospectively evaluated adult patients with achalasia types 1, 2, 3, EGJ outflow obstruction (EGJOO) or normal motility on high-resolution manometry who underwent endoscopic ultrasound (EUS) from January 2019 to August 2022. Thickened circular muscle was defined as ≥1.6 mm. Characteristics from barium esophagram (BE) and functional lumen imaging probe (FLIP) were additionally assessed. KEY RESULTS: Of 71 patients (mean age 56.2 years; 49% male), there were 8 (11%) normal motility, 58 (82%) had achalasia (5 (7%) type 1, 32 (45%) classic type 2, 21 (30%) type 3 [including 12 type 2 with FEPs]), and 7 (7%) had EGJOO. A significantly greater proportion of type 3 achalasia had thickened distal circular muscle (76.2%) versus normal motility (0%; p < 0.001) or type 2 achalasia (25%; p < 0.001). Type 1 achalasia had significantly wider mean maximum esophageal diameter on BE (57.8 mm) compared to type 2 achalasia (32.8 mm), type 3 achalasia (23.4 mm), EGJOO (15.9 mm), and normal motility (13.5 mm). 100% type 3 achalasia versus 0% type 1 achalasia/normal motility had tertiary contractions on BE. Mean EGJ distensibility index on FLIP was lower for type 3 achalasia (1.2 mmHg/mm2 ) and EGJOO (1.2 mmHg/mm2 ) versus type 2 (2.3 mmHg/mm2 ) and type 1 achalasia (2.9 mmHg/mm2 ). CONCLUSIONS: Our findings suggest distinct pathologic pathways may exist: type 3 achalasia and EGJOO may represent a spastic outflow phenotype consisting of a thickened, spastic circular muscle, which is distinct from type 1 and 2 achalasia consisting of a thin caliber circular muscle layer with more prominent esophageal dilation.

Diagnostic methods to measure spastic segment and guide tailored myotomy length in type 3 achalasia.

BACKGROUND: Myotomy length in type 3 achalasia is generally tailored based on segment of spasticity on high-resolution manometry (HRM). Potential of length of tertiary contractions on barium esophagram (BE) or length of thickened circular muscle on endoscopic ultrasound (EUS) to guide tailored myotomy is less understood. This study aimed to assess agreement between spastic segments lengths on HRM, BE, and EUS among patients with type 3 achalasia. METHODS: This retrospective study included adults with type 3 achalasia on HRM between November 2019 and August 2022 who underwent evaluation with EUS and/or BE. Spastic segments were defined as HRM-distance between proximal borders of lower esophageal sphincter and high-pressure area (isobaric contour ≥70 mmHg); EUS-length of thickened circular muscle (≥1.2 mm) from proximal border of esophagogastric junction (EGJ) to the transition to a non-thickened circular muscle; BE-distance between EGJ to proximal border of tertiary contractions. Pairwise comparisons assessed for correlation (Pearson's) and intraclass correlation classification (ICC) agreement. KEY RESULTS: Twenty-six patients were included: mean age 66.9 years (SD 13.8), 15 (57.7%) male. Spastic segments were positively correlated on HRM and BE with good agreement (ICC 0.751, [95% CI 0.51, 0.88]). Spastic segments were negatively correlated with poor agreement on HRM and EUS (ICC -0.04, [-0.45, 0.39]) as well as BE and EUS (ICC -0.03, [-0.47, 0.42]). CONCLUSIONS & INFERENCES: Length of spastic segment was positively correlated on HRM and BE while negatively correlated when compared to EUS, supporting the common use of HRM and highlighting the uncertain role for EUS in tailoring myotomy length for type 3 achalasia.

Impact of COVID-19 infection and vaccination in pancreatobiliary IgG4-related disease patients: An international multicenter study.

BACKGROUND AND AIM: Dedicated studies evaluating the impact of COVID-19 on outcomes of pancreatobiliary IgG4 related disease (IgG4-RD) patients are scarce. Whether COVID-19 infection or vaccination would trigger IgG4-RD exacerbation remains unknown. METHODS: Pancreatobiliary IgG4-RD patients ≥ 18 years old with active follow-up since January 2020 from nine referral centers in Asia, Europe, and North America were included in this multicenter retrospective study. Outcome measures include incidence and severity of COVID-19 infection, IgG4-RD disease activity and treatment status, interruption of indicated IgG4-RD treatment. Prospective data on COVID-19 vaccination status and new COVID-19 infection during the Omicron outbreak were also retrieved in the Hong Kong cohort. RESULTS: Of the 124 pancreatobiliary IgG4-RD patients, 25.0% had active IgG4-RD, 71.0% were on immunosuppressive therapies and 80.6% had ≥ 1 risk factor for severe COVID. In 2020 (pre-vaccination period), two patients (1.6%) had COVID-19 infection (one requiring ICU admission), and 7.2% of patients had interruptions in indicated immunosuppressive treatment for IgG4-RD. Despite a high vaccination rate (85.0%), COVID-19 infection rate has increased to 20.0% during Omicron outbreak in the Hong Kong cohort. A trend towards higher COVID-19 infection rate was noted in the non-fully vaccinated/unvaccinated group (17.6% vs 33.3%, P = 0.376). No IgG4-RD exacerbation following COVID-19 vaccination or infection was observed. CONCLUSION: While a low COVID-19 infection rate with no mortality was observed in pancreatobiliary IgG4-RD patients in the pre-vaccination period of COVID-19, infection rate has increased during the Omicron outbreak despite a high vaccination rate. No IgG4-RD exacerbation after COVID-19 infection or vaccination was observed.

Type II achalasia with focal elevated pressures: A distinct manometric and clinical sub-group.

BACKGROUND: Type II achalasia (Ach2) is distinguished from other achalasia sub-types by the presence of panesophageal pressurization (PEP) of ≥30 mmHg in ≥20% swallows on high-resolution manometry (HRM). Variable manometric features in Ach2 have been observed, characterized by focal elevated pressures (FEPs) (focal/segmental pressures ≥70 mmHg within the PEP band) and/or high compression pressures (PEP ≥70 mmHg). This study aimed to examine clinical and physiologic variables among sub-groups of Ach2. METHODS: This retrospective single center study performed over 3 years (1/2019-1/2022) included adults with Ach2 on HRM who underwent endoscopic ultrasound (EUS), functional lumen imaging probe (FLIP), and/or barium esophagram (BE) prior to therapy. Patients were categorized into two overarching sub-groups: Ach2 without FEPs and Ach2 with FEPs. Demographic, clinical, and physiologic data were compared between these sub-groups utilizing unpaired univariate analyses. KEY RESULTS: Of 53 patients with Ach2, 40 (75%) were without FEPs and 13 (25%) had FEPs. Compared with the Ach2 sub-group without FEPs, the Ach2 sub-group with FEPs demonstrated a significantly thickened distal esophageal circular muscle on EUS (1.4 mm [SD 0.9] vs. 2.1 [0.7]; p = 0.02), higher prevalence of tertiary contractions on BE (46% vs. 100%; p = 0.0006), lower esophagogastric junction distensibility index (2.2mm2 /mmHg [0.9] vs 0.9 [0.4]; p = 0.0008) as well as higher distensive pressure (31.0 mmHg [9.8] vs. 55.4 [18.8]; p = 0.01) at 60 cc fill on FLIP, and higher prevalence of chest pain on Eckardt score (p = 0.03). CONCLUSIONS AND INFERENCES: We identified a distinct sub-group of type II achalasia on HRM, defined as type II achalasia with focal elevated pressures. This sub-group uniquely exhibits spastic features and may benefit from personalized treatment approaches.

Evolution and evidence-based adaptations in techniques for peroral endoscopic myotomy for achalasia.

Achalasia is an esophageal motility disorder characterized by impaired lower esophageal sphincter (LES) relaxation and failed peristalsis. Common clinical manifestations include dysphagia to solid and liquid foods, chest pain, regurgitation, and weight loss, resulting in significant morbidity and healthcare burden. Historically, surgical Heller myotomy and pneumatic dilation were the first-line therapeutic options for achalasia. This convention was shaken in 2009 when Inoue and colleagues introduced an endoscopic approach to dissect the muscle fibers of the LES, known as peroral endoscopic myotomy (POEM). Since incorporation of POEM into standard practice, the overall myotomy technique has remained unchanged; however, adaptations in the thickness and length of myotomy have evolved. Full-thickness myotomy is recognized to have similar clinical success and faster procedure times compared with selective circular muscle myotomy. Although myotomy length for type 1 and type 2 achalasia has classically been >6 cm, recent studies demonstrated similar outcomes with reduction of myotomy length to <3 cm. Length of myotomy for type 3 achalasia has been tailored to treat the entire length of spastic muscle segment, and the modality to gauge the optimal thickness and length of myotomy in this group has yet to be established. In addition to changes in POEM technique, the postoperative management of POEM has also changed, favoring reduced postprocedure imaging, antibiotic use, and hospitalizations.

Microbiome of the Aerodigestive Tract in Health and Esophageal Disease.

The diverse human gut microbiome is comprised of approximately 40 trillion microorganisms representing up to 1000 different bacterial species. The human microbiome plays a critical role in gut epithelial health and disease susceptibility. While the interaction between gut microbiome and gastrointestinal pathology is increasingly understood, less is known about the interaction between the microbiome and the aerodigestive tract. This review of the microbiome of the aerodigestive tract in health, and alterations in microbiome across esophageal pathologies highlights important findings and areas for future research. First, microbiome profiles are distinct along the aerodigestive tract, spanning the oral cavity to the stomach. In patients with reflux-related disease such as gastro-esophageal reflux disease, Barrett's esophagus, and esophageal adenocarcinoma, investigators have observed an overall increase in gram negative bacteria in the esophageal microbiome compared to healthy individuals. However, whether differences in microbiome promote disease development, or if these shifts are a consequence of disease remains unknown. Interestingly, use of proton pump inhibitor therapy is also associated with shifts in the microbiome, with distinct shifts and patterns along the aerodigestive tract. The relationship between the human gut microbiome and esophageal pathology is a ripe area for investigation, and further understanding of these pathways may promote development of novel targets in prevention and therapy for esophageal diseases.

Overview and comparison of guidelines for management of pancreatic cystic neoplasms.

Pancreatic cysts are identified at an increasing frequency. Although mucinous cystic neoplasms represent a pre-malignant condition, the majority of these lesions do not progress to cancer. Over the last 10 years several societies have established guidelines for the diagnosis, initial evaluation and surveillance of these lesions. Here we provide an overview of five commonly used guidelines: 2015 American Gastroenterological Association, 2017 International Association of Pancreatology, American College of Gastroenterology 2018, European Study Group and American College of Radiology. We describe the similarities and differences between the methods used to formulate these guidelines, the population they target and their approaches towards initial evaluation and surveillance of cystic lesions.

Systematic review of modifiable risk factors for kidney cancer.

To perform a systematic review of modifiable risk factors associated with the incidence of renal cell cancer (RCC). A systematic search of the literature was conducted using PubMed, Cochrane, and Web of Science databases from January 1996 until August 2017. We also extracted articles from the reference lists of identified studies and reviews. We targeted modifiable risk factors for RCC to include exercise, smoking, alcohol, diet, obesity, hypertension, and diabetes. We utilized predefined inclusion criteria and the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. We identified a total of 464 relevant articles and excluded 209 via title and 130 after abstract review. We thoroughly reviewed a total of 125 manuscripts. Seven supplementary tables describe (a) case controls and (b) prospective cohort studies. We summarize the tables in figures to visualize the overall impact of these studies association (beneficial, harmful, or null) with RCC. Total physical activity if beneficial (10/12 studies), smoking is harmful (13/14 studies), alcohol was protective (i.e., beneficial, 13/16 studies), diet was indeterminate (13 beneficial, 13 harmful, and 9 nulls), obesity and hypertension were overwhelmingly harmful (36/36 studies and 17/18, respectively), and diabetes was detrimental (23/27 studies). Modifiable risk factors play an essential role in the development of RCC, and we should develop targeted RCC prevention strategies in at-risk individuals.

Predictors of Survival for Patients with Acute Decompensated Heart Failure Requiring Extra-Corporeal Membrane Oxygenation Therapy.

Chronic systolic heart failure (HF) with acute decompensation can result in cardiogenic shock (CS) requiring short-term mechanical circulatory support. We sought to identify predictors of survival for acute decompensated HF (ADHF) patients requiring veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Patients >18 years old treated at our institution with VA-ECMO from 2009 to 2018 for ADHF with CS were studied. Demographic, hemodynamic, and echocardiographic data were collected. The primary outcome was survival to discharge. Fifty-two patients received VA-ECMO for ADHF with CS; 24 (46.2%) survived. Seventeen (32.7%) had suffered cardiac arrest, and 37 (71.2%) were mechanically ventilated. Mean lactate was 4.33 ± 3.45 mmol/L, and patients were receiving 2.7 ± 1.2 vasopressor/inotropic infusions at ECMO initiation; these did not differ significantly between survivors and nonsurvivors. Pre-ECMO cardiac index was 1.84 ± 0.56L/min/m and 1.94 ± 0.63L/min/m in survivors and nonsurvivors, respectively (p = 0.57). In multivariable analysis, only diabetes mellitus (DM; OR, 13.25; CI, 1.42-123.40; p = 0.02) and mineralocorticoid receptor antagonist use (OR, 0.12; CI, 0.02-0.78; p = 0.03) were independent predictors of mortality. Nineteen (79.2%) survivors required durable ventricular assist device. Among ADHF patients receiving VA-ECMO, DM is a powerful predictor of outcomes while markers of clinical acuity including hemodynamics, vasopressor/inotrope use, and lactate are not. The vast majority of survivors required durable left-ventricular assist devices.

The Role of Genetics in Pancreatitis.

Individuals with acute recurrent and chronic pancreatitis may have an inherited predisposition to the development of the disease. Pancreatitis in the setting of a significant family history of the disease can be classified as hereditary or familial pancreatitis. In this article, the authors closely examine the specific genes implicated in pancreatitis, investigate the role of genetic testing for diagnosis, and describe the impact of genetic testing results on clinical management.

Physical Activity Decreases Kidney Cancer Mortality.

BACKGROUND: To investigate associations of kidney cancer mortality with modifiable risk factors of obesity, physical activity, and smoking. METHODS: We evaluate baseline data from US National Health Information Survey from 1998 through 2004 linked to mortality data reporting deaths through 2006. The primary outcome variable was kidney cancer-specific mortality and primary exposure variables were self-reported physical activity and body mass index (BMI). We utilized multivariable adjusted Cox proportional hazards regression models, with delayed entry to account for age at survey interview. RESULTS: Among 222,163 individuals with complete follow-up data we identified 71 kidney cancer-specific deaths. In multivariate analyses, individuals who reported "any physical activity" were 50% less likely [adjusted hazard ratio (adjusted HR) 0.50, 95% CI 0.27-0.93, p = 0.028] to die of kidney cancer than non-exercisers, while obese individuals (BMI ≥ 30 kg/m2) were nearly 3 times more likely (adjusted HR 2.84, 95% CI 1.30-6.23, p = 0.009) compared to those of normal weight (BMI < 25 kg/m2). Compared to never smokers, former smokers were twice as likely to die of kidney cancer (adjusted HR 2.00, 95% CI 1.05-3.80, p = 0.034). CONCLUSION: Physical activity decreases and obesity increases the risk of kidney cancer mortality.

Improving nutritional status in a pediatric cystic fibrosis center.

BACKGROUND: The nutritional status of patients with cystic fibrosis (CF) is strongly associated with pulmonary function, respiratory status and survival. Malnutrition could result from a discrepancy between energy needs and food intake while malabsorption results from pancreatic insufficiency which occurs in 85% of people with CF. METHODS: A quality improvement (QI) project was designed to improve the nutritional status of patients with CF with low Body Mass Index (BMI) between 3 and 19 years of age. An algorithm was developed which included clinic-based assessments of patients' nutritional status and periodic assessment by a dietitian, social worker and/or psychologist during the project. Gastrostomy tube placement and feeding was offered as a last resort to improve caloric intake. RESULTS: 173 patients seen during January-June, 2010, were included in this project. They were classified into four BMI groups and data were collected quarterly through June, 2012. The project target population (BMI percentile ≤ 24) had a median BMI percentile at the start of the project of 11.8. At the end of the project median BMI percentile was 22 (46% improvement). CONCLUSION: Improving nutrition and BMI for patients with CF is achievable. There must be a motivated, multi-disciplinary team that includes patients and families. A patient-specific combination of interventions must be used. These interventions could be quite basic for patients with BMI percentile ≥ 25, yet more elaborate for patients with BMI percentile <25. Clinic-based algorithms such as ours can successfully improve the BMI percentile in patients with CF.