Noninvasive biomarkers for the detection of GERD-induced pulmonary injury.

BACKGROUND: The role of gastroesophageal reflux in progressive lung damage is increasingly recognized. We have proposed, based on our work with lung transplant recipients, a novel immune mechanism of pulmonary injury after aspiration of gastric contents, during which higher levels of normally sequestered lung self-antigens (SAgs) collagen V (Col-V) and K-alpha-1 tubulin (Kα1T) in circulating small extracellular vesicles (EVs) induce the production of self-antibodies (SAbs) anti-Col-V and anti-Kα1T. Thus, we aimed to determine whether levels of SAbs or SAgs increased in an animal model of aspiration-induced lung damage in a nontransplant setting. METHODS: We created a murine model of repetitive lung aspiration using C57BL/6J mice. Mice were aspirated weekly with 1 mL/kg of hydrochloric acid (n = 9), human gastric contents (n = 9), or combined (1:1) fluid (n = 9) once, three, or six times (n = 3 in each subgroup; control group, n = 9). Blood samples were periodically obtained, and all animals were sacrificed at day 90 for pathological assessment. SAbs were measured using an enzyme-linked immunosorbent assay; SAgs and NF-κB contained in small EVs were assessed by western blot. RESULTS: Aspirated mice weighed significantly less than controls throughout the study and had histological evidence of pulmonary injury at day 90. Overall, aspirated mice developed higher concentrations of anti-Col-V at day 28 (53.9 ± 28.7 vs. 29.9 ± 4.5 ng/mL, p < 0.01), day 35 (42.6 ± 19.8 vs. 28.6 ± 7.2 ng/mL, p = 0.038), and day 90 (59.7 ± 27.7 vs. 34.1 ± 3.2 ng/mL, p = 0.014) than the control group. Circulating small EVs isolated from aspirated mice on day 90 contained higher levels of Col-V (0.7 ± 0.56 vs. 0.18 ± 0.6 m.o.d., p = 0.009) and NF-κB (0.42 ± 0.27 vs. 0.27 ± 0.09 m.o.d., p = 0.095) than those from controls. CONCLUSIONS: This experimental study supports the theory that gastroesophageal reflux leads to the development of lung damage and an increase of humoral markers that may serve as noninvasive biomarkers to detect asymptomatic lung injury among patients with gastroesophageal reflux disease.

Adoption of telemedicine for obesity treatment during the COVID-19 pandemic achieved comparable outcomes to in-person visits.

Background: During the COVID-19 pandemic, weight loss programs rapidly transitioned to a virtual model, replacing in-person clinic visits. We sought to compare the observed weight loss and adherence to treatment between patients referred for intensive behavioral therapy (IBT) who were treated via telemedicine and those treated in person. Methods: After IRB approval, we conducted a retrospective observational study of patients referred for clinical bariatric IBT between January 2019 and June 2021 who were followed in person or via telemedicine. The primary endpoint was the percentage of excess BMI loss (EBL%); secondary endpoints included treatment adherence, duration of follow-up, and number of completed visits. Results: During the study period, 139 patients were seen for at least one IBT session for weight management: 62 were followed up in person (IP) and 77 via telemedicine (TM). The mean age, baseline BMI, and follow-up duration between the groups were similar. In the IP and TM groups, the EBL% was -24.7 ± 24.7 and -22.7 ± 19.5 (P = 0.989) and loss to follow-up after the first visit was 27.4% and 19.5% (P = 0.269), respectively. Conclusion: For the management of obesity, weight loss programs delivered via telemedicine can achieve similar outcomes to those provided via classical in-person visits. This study suggests that the integration of telecare into clinical practice in bariatric medicine should be considered in the future. Emerging technologies may allow adequate patient follow-up in multiple scenarios, specifically non-critical chronic disorders, and bring unanticipated benefits for patients and healthcare providers.

pHoenix score: development and validation of a novel approach to decrease the number of inconclusive GERD diagnoses.

BACKGROUND: The Johnson-DeMeester composite score (DMS) is the historical gold standard for diagnosing gastroesophageal reflux disease (GERD). The Lyon Consensus outlines criteria for diagnosing GERD by pH monitoring, defining normal acid exposure time (AET) as < 4% and pathological as > 6%, presenting diagnostic uncertainty from 4 to 6%. We aimed to (i) calculate the proportion of borderline studies defined by total AET alone that are reclassified as normal or pathological by the DMS, (ii) determine the importance of supine AET for reclassification, and (iii) propose a new classification system using a composite score that considers positional changes. METHODS: This single-center, retrospective, observational study analyzed data from patients with an overall total AET from 2 to 6% on 48-h pH monitoring (Bravo pH capsule). Preselected predictors (supine and upright AET) were included in a model to create a composite score (i.e., pHoenix score) using the regression coefficients. The model was internally validated, and discriminative ability was tested against the DMS and compared to the total AET. RESULTS: We identified 114 patients (80 [70.2%] women; median age, 55 years). Using the total AET, 26 (22.8%) were classified as normal and 88 (77.2%) as borderline; however, using the DMS, 45 (39.5%) were classified as normal and 69 (60.5%) as pathological. The new pHoenix score demonstrated strong discriminative ability (AUC: 0.957 [95% CI 0.917, 0.998]) with high sensitivity and specificity (lower threshold, 94.4% and 79.2%; upper threshold, 87 and 95.8%). Compared to the total AET alone, the pHoenix score significantly decreased the proportion of inconclusive cases (77.2% vs. 13.2%, p < 0.001). CONCLUSION: Total AET has low sensitivity to identify pathological reflux as it disregards supine versus upright reflux. The pHoenix score improves the distinction between normal and pathological cases and reduces ambiguity, offering an alternative approach to diagnosing GERD that addresses the limitations of using total AET alone or the DMS.

Endoscopic assessment of failed fundoplications differs between endoscopists.

BACKGROUND: Despite excellent long-term outcomes, a small proportion of patients who undergo fundoplication with hiatal hernia repair (laparoscopic antireflux surgery [ARS]) for treatment of gastroesophageal reflux disease (GERD) may require reoperation. Esophagogastroduodenoscopy (EGD) assessment in patients presenting with symptom recurrence plays a critical role in surgical planning of redo-ARS by confirming failure of the fundoplication and revealing the pattern of failure. We aimed to compare the findings documented by external endoscopists (i.e., outside physicians) to those documented by internal endoscopists (i.e., operating foregut or thoracic surgeons) before redo-ARS. METHODS: After IRB approval, we conducted a retrospective chart review of patients who underwent redo-ARS at a tertiary surgical center between November 2016 and March 2023. Patients with both external and internal EGD reports were included, and findings from the two reports were compared. RESULTS: Of 197 patients who underwent redo-ARS, both preoperative EGD reports were available for 181 (136 [75.1%] women; median age, 61 years [IQR 53-69]; median BMI, 27.9 kg/m2 [IQR 24.9-31.3]). The median time between primary and redo-ARS was 89 months (IQR 38-153), and the median time between external and internal endoscopic evaluation was 5 months (IQR 2-12). Only 38.9% of external reports mentioned a prior fundoplication. Compared to the operating surgeons, external physicians reported a significantly lower proportion of Barrett's esophagus (52.4%, p < .001), slipped fundoplications (28.8%, p < .001), paraesophageal hernias (20.5%, p < .001), disrupted fundoplications (20%, p < .001), intrathoracic fundoplications (0%, p < .001), and twisted fundoplications (0%, p < .001). CONCLUSIONS: External endoscopists' reports of failed fundoplications are often incomplete and lack relevant details. Discrepancies between nonsurgical endoscopists and experienced surgeons are likely explained by a lack of training and experience to discern and document fundoplication changes accurately. To reduce this gap, we strongly recommend the adoption of standard definitions describing post-fundoplication endoscopic changes and the inclusion of relevant training within educational programs.

Impaired esophagogastric junction relaxation and lung transplantation outcomes.

The implications of impaired esophagogastric junction relaxation (i.e. esophagogastric junction outflow obstruction and achalasia) in lung transplants recipients (LTRs) are unclear. Thus, we examined the prevalence and clinical outcomes of LTRs with an abnormally elevated integrated relaxation pressure (IRP) on high-resolution manometry before lung transplantation (LTx). After IRB approval, we reviewed data on LTRs who underwent LTx between January 2019 and August 2022 with a preoperative median IRP >15 mmHg. Differences in overall survival and chronic lung allograft dysfunction (CLAD)-free survival between LTRs with a normalized median IRP after LTx (N-IRP) and those with persistently high IRP (PH-IRP) were assessed using Kaplan-Meier curves and the log-rank test. During the study period, 352 LTx procedures were performed; 44 (12.5%) LTRs had an elevated IRP before LTx, and 37 (84.1%) completed a postoperative manometry assessment (24 [70.6%] males; mean age, 65.2 ± 9.1 years). The median IRP before and after LTx was 18.7 ± 3.8 mmHg and 12 ± 5.6 mmHg, respectively (P < 0.001); the median IRP normalized after LTx in 24 (64.9%) patients. Two-year overall survival trended lower in the N-IRP group than the PH-IRP group (77.2% vs. 92.3%, P = 0.086), but CLAD-free survival (P = 0.592) and rates of primary graft dysfunction (P = 0.502) and acute cellular rejection (P = 0.408) were similar. An abnormally elevated IRP was common in LTx candidates; however, it normalized in roughly two-thirds of patients after LTx. Two-year survival trended higher in the PH-IRP group, despite similar rates of primary graft dysfunction and acute cellular rejection as well as similar CLAD-free survival between the groups.

Cruroplasty with or without mesh? A systematic literature review with a novel time-organized proportion meta-analysis.

BACKGROUND: Improved outcomes with the use of non-absorbable mesh (NAM) for inguinal hernia repairs led to its rapid adoption for hiatal hernia (HH) repairs; however, feared complications occurred, and the trend shifted toward using absorbable mesh (AM). We aimed to analyze the literature assessing objective HH recurrence rates after primary laparoscopic cruroplasty with or without the use of different mesh types. METHODS: A systematic literature review with both pairwise and time-organized proportion meta-analyses of articles published between January 1993 and September 2022 was performed using the MEDLINE, EMBASE, and Taylor & Francis databases to identify relevant studies comparing groups undergoing cruroplasty with suture repair (SR) alone, AM, NAM, or partially absorbable mesh (PAM). Studies documenting an objective follow-up ≥ 6 months were included. The primary outcome was the HH recurrence rate confirmed by barium esophagram or upper GI endoscopy. RESULTS: A total of 34 studies met the inclusion criteria, including 6 randomized clinical trials, 25 retrospectives studies, and 3 prospective cohort studies. A total of 2170 subjects underwent laparoscopic HH repair and completed an objective follow-up ≥ 6 months after surgery; the objective recurrence rate was 20.8% (99/477) at a mean follow-up of 25.8 ± 16.4 months for the SR group, 20.6% (244/1187) at 28.1 ± 13.8 months for the AM group, 13.7% (65/475) at 30.8 ± 15.3 months for the NAM group, and 0% (0/31) at 32.5 ± 13.5 months for the PAM group. However, the pairwise meta-analysis revealed that overall mesh use was not superior to SR in preventing long-term HH recurrence. CONCLUSION: The use of AM does not appear to reduce HH recurrence compared to SR alone. Although the data favors NAM to decrease objective HH recurrence in the mid-term, the long-term (≥ 48 months) recurrence rate was similar with or without any type of mesh.

Brief guidelines for beginners on how to perform and analyze esophageal high-resolution manometry.

High-resolution manometry (HRM) is a diagnostic tool for surgeons, gastroenterologists and other healthcare professionals to evaluate esophageal physiology. The Chicago Classification (CC) system is based on a consensus of worldwide experts to minimize ambiguity in HRM data acquisition and diagnosis of esophageal motility disorders. The most updated version, CCv4.0, was published in 2021; however, it does not provide step-by-step guidelines (i.e., for beginners) on how to assess the most important HRM metrics. This paper aims to summarize the basic guidelines for conducting a high-quality HRM study including data acquisition and interpretation, based on CCv4.0, using Manoview ESO analysis software, version 3.3 (Medtronic, Minneapolis, MN).

Prevalence and severity of abdominal bloating in patients with gastroesophageal reflux disease.

Abdominal bloating (AB) is a common symptom among patients with gastroesophageal reflux disease (GERD); however, in clinical practice, its prevalence is likely underestimated due to the lack of objective tools to measure its frequency and severity. It is associated with dissatisfaction and worse quality of life, but data on its prevalence before and after mechanical control of GERD (i.e. fundoplication, magnetic sphincter augmentation, and antireflux mucosectomy) are lacking. To assess and determine the pre- and postoperative prevalence and severity of AB among patients with GERD, we conducted a structured literature search using MeSH and free-text terms in MEDLINE (via Pubmed), EMBASE, and Taylor & Francis Online between January 1977 and October 2022. Fifteen articles reporting the prevalence or severity of AB using quality-of-life questionnaires before or after antireflux surgery (ARS) were included. Overall, a high prevalence of AB before ARS was found. A decline in the prevalence and severity of AB was documented postoperatively in most cases independent of the surgical approach. Among surgical approaches, a complete fundoplication had the highest reported postoperative AB. Overall, patients reported less severe and less frequent AB after ARS than before. The traditional belief that postoperative bloating is a sequela of ARS should be reevaluated.

Pulmonary and esophageal function in lung transplantation: Fundamental principles and clinical application.

The lungs and esophagus have a close anatomical and physiological relationship. Over the years, reflux-induced pulmonary injury has gained wider recognition, but the full effects of pulmonary disease on esophageal function are still unknown. Intrathoracic pressure dynamics potentially affect esophageal function, especially in patients with end-stage lung disease, both obstructive and restrictive. Lung transplantation is the only viable option for patients with end-stage pulmonary disease and has provided us with a unique opportunity to study these effects as transplantation restores the intrathoracic environment. Esophageal and foregut functional testing before and after transplantation provide insights into the pathophysiology of the foregut-pulmonary axis, such as how underlying pulmonary disease and intrathoracic pressure changes affect esophageal physiology. This review summarizes the available literature and shares the research experience of a lung transplant center, covering topics such as pre- and posttransplant foregut function, esophageal motility in lung transplant recipients, immune-mediated mechanisms of graft rejection associated with gastroesophageal reflux, and the role of antireflux surgery in this population.

Diagnosis and management of anastomotic leaks after Ivor Lewis esophagectomy: a single-center experience.

PURPOSE: Esophageal anastomotic leaks (ALs) after esophagectomy are a common and serious complication. The incidence, diagnostic approach, and management have changed over time. We described the diagnosis and management of patients who developed an esophageal AL after an Ivor Lewis esophagectomy at our center. METHODS: After IRB approval, we queried our prospectively maintained database for patients who developed an esophageal AL after esophagectomy from August 2016 through July 2022. Data pertaining to demographics, comorbidities, surgical and oncological characteristics, and clinical course were extracted and analyzed. RESULTS: During the study period, 145 patients underwent an Ivor Lewis esophagectomy; 10 (6.9%) developed an AL, diagnosed a median of 7.5 days after surgery, and detected by enteric contents in wound drains (n = 3), endoscopy (n = 3), CT (n = 2), and contrast esophagogram (n = 2). Nine patients (90%) had an increasing white blood cell count and additional signs of sepsis. One asymptomatic patient was identified by contrast esophagography. All patients received enteral nutritional support, intravenous antibiotics, and antifungals. Primary treatment of ALs included endoscopic placement of a self-expanding metal stent (SEMS; n = 6), surgery (n = 2), and SEMS with endoluminal vacuum therapy (n = 2). One patient required surgery after SEMS placement. The median length of ICU and total hospital stays were 11.5 and 22.5 days, respectively. There was no 30-day mortality. CONCLUSION: The incidence of esophageal ALs at our center is similar to that of other high-volume centers. Most ALs can be managed without surgery; however, ALs remain a significant source of postoperative morbidity despite clinical advancements that have improved mortality.

Surgical Repair of Large Hiatal Hernias: Insight from a High-Volume Center.

BACKGROUND: Laparoscopic-assisted hiatal hernia (HH) repair is safe and effective; however, it is unclear whether hernia size affects perioperative outcomes and whether a watch-and-wait strategy is appropriate for patients with asymptomatic large HHs. We aimed to investigate these issues. METHODS: After IRB approval, we queried our prospectively maintained database for patients who underwent primary laparoscopic HH repair at our center between August 2016 and December 2019. All procedures were performed by a single surgeon (SKM). According to the intraoperative findings, HHs were divided into four groups: small (S-HH), medium (M-HH), large (L-HH), or giant (G-HH) when the percentage of herniated stomach was 0% (sliding), < 50%, 50-75%, or > 75%, respectively. Perioperative and mid-term outcomes were analyzed. RESULTS: A total of 170 patients were grouped: S-HH (n = 46), M-HH (n = 69), L-HH (n = 20), and G-HH (n = 35) with mean age of 58.5.6 ± 11.0, 61.9 ± 11.3, 70.7 ± 10.3, and 72.6 ± 9.7 years (p < 0.001), respectively. Compared to M-HH patients, L-HH patients had significantly longer hospital stays (mean 2.8 ± 3.2 vs 1.4 ± 0.91 days; p = 0.001) and more postoperative complications (6/20 [30.0%] vs 3/69 [4.3%]; OR 6.9, 95% CI 5.4-8.4, p < 0.001). At a mean follow-up time of 43.1 ± 25.0 and 43.5 ± 21.6 months for the combined S/M-HH and L/G-HH groups, GERD-Health-Related Quality of Life scores were comparable (S/M-HH: 6.5 ± 10.9 vs L/G-HH: 7.1 ± 11.3; p = 0.63). There was no perioperative mortality. CONCLUSIONS: HHs likely grow with age, reflecting their progressive nature. Laparoscopic L-HH repair was associated with higher morbidity than M-HH repair. Thus, patients with M-HH, even if less symptomatic, should be evaluated by a foregut surgeon. Regardless of HH size, good mid- and long-term quality of life outcomes can be achieved.

Magnetic sphincter augmentation may limit access to magnetic resonance imaging.

Magnetic sphincter augmentation (MSA) is an alternative surgical treatment for gastroesophageal reflux disease; however, >1.5 T magnetic resonance imaging (MRI) is contraindicated for patients who have undergone MSA with the LINX Reflux Management System (Torax Medical, Inc. Shoreview, Minnesota, USA). This drawback can impose a barrier to access of MRI, and cases of surgical removal of the device to enable patients to undergo MRI have been reported. To evaluate access to MRI for patients with an MSA device, we conducted a structured telephone interview with all diagnostic imaging providers in Arizona in 2022. In 2022, only 54 of 110 (49.1%) locations that provide MRI services had at least one 1.5 T or lower MRI scanner. The rapid replacement of 1.5 T MRI scanners by more advanced technology may limit healthcare options and create an access barrier for patients with an MSA device.

Magnetic sphincter augmentation for gastroesophageal reflux in overweight and obese patients.

Magnetic sphincter augmentation (MSA) is a successful treatment option for chronic gastroesophageal reflux disease; however, there is a paucity of data on the efficacy of MSA in obese and morbidly obese patients. To assess the relationship between obesity and outcomes after MSA, we conducted a literature search using MeSH and free-text terms in MEDLINE, EMBASE, Cochrane and Google Scholar. The included articles reported conflicting results regarding the effect of obesity on outcomes after MSA. Prospective observational studies with larger sample sizes and less statistical bias are necessary to understand the effectiveness of MSA in overweight and obese patients.