INTRODUCTION:Barrett esophagus (BE) is the strongest known risk factor for developing esophageal adenocarcinoma (EAC), the second-most lethal cancer in the United States. Esopredict is a novel validated methylation-based biomarker assay that provides precise quantification of neoplastic progression risk in BE patients. Inherit challenges, including tissue heterogeneity, sampling error, interobserver variability, and inconsistent adherence to surveillance biopsy guidelines, may affect the predictive value results of Esopredict obtained at different anatomic locations or different sampling time points.METHODS:To investigate the spatiotemporal performance of Esopredict across multiple spatiotemporal sampling points, we profiled 220 biopsies obtained from 58 BE patients, including 11 patients with overlapping spatial and temporal biopsies. We focused on spatial profiling (i.e., multiple biopsies obtained at several anatomic locations during a single endoscopy) and temporal profiling (i.e., biopsies obtained from multiple endoscopies performed at different time points). Each patient had an initial histologic diagnosis of nondysplastic Barrett esophagus, indefinite for dysplasia, or low-grade dysplasia. Final follow-up (endpoint) biopsies showed either high-grade dysplasia or EAC (progressors), or nondysplastic Barrett esophagus, indefinite for dysplasia, or low-grade dysplasia (nonprogressors). Biopsies were analyzed with Esopredict to compute a progression risk score, which quantified the likelihood of future progression to high-grade dysplasia or EAC within 5 years.RESULTS:In 52 spatially profiled patients, Esopredict demonstrated a sensitivity of 81% (17/21 progressor patients), based on the highest-scoring biopsy from each patient; sensitivity increased to 100% (12/12) when end point biopsies occurred within 5 years of the index (initial) biopsy. In 28 temporally profiled patients, sensitivity was 100% (8/8 patients), based on the biopsy performed at the time point closest to the end point biopsy.DISCUSSION:Esopredict showed high predictive performance in multiple spatiotemporal samples in BE patients. These data further support the use of Esopredict as a robust test to distinguish high-risk BE patients, who may benefit from endoscopic eradication therapy or increased surveillance frequency, from low-risk patients, who may be candidates for less frequent surveillance and noninterventional observation.

Ischemic colitis (IC) should be considered as a cause for gastrointestinal symptoms in patients with recent vigorous physical activity. Vasoconstriction driven by increased sympathetic tone during exercise is believed to mediate exercise-induced IC. In this report, a 21-year-old man with no medical history developed self-resolving, sudden-onset hematochezia and abdominal pain after playing in a collegiate soccer match for 90 minutes. Colonoscopy with biopsy showed changes consistent with IC. He improved without further treatment. In most cases, exercise-induced IC resolves completely with supportive care and correction of hypovolemia. Careful monitoring is appropriate before pursuing further evaluation.

INTRODUCTION: Esophageal adenocarcinoma (EAC) is the second-most lethal cancer in the United States, with Barrett esophagus (BE) being the strongest risk factor. Assessing the future risk of neoplastic progression in patients with BE is difficult; however, high-grade dysplasia (HGD) and early EAC are treatable by endoscopic eradication therapy (EET), with survival rates of 90%. Thus, it would be beneficial to develop a molecular assay to identify high-risk patients, who merit more frequent endoscopic surveillance or EET, as well as low-risk patients, who can avoid EET and undergo less frequent surveillance. METHODS: Deidentified endoscopic biopsies were acquired from 240 patients with BE at 6 centers and confirmed as future progressors or nonprogressors. Tissues were analyzed by a set of methylation-specific biomarker assays. Test performance was assessed in an independent validation set using 4 stratification levels: low risks, low-moderate risks, high-moderate risks, and high risks. RESULTS: Relative to patients in the low-risk group, high-risk patients were 15.2 times more likely to progress within 5 years to HGD or EAC. For patients in the high-risk category, the average risk of progressing to HGD or EAC within 5 years was 21.5%, 4-fold the BE population prevalence within 5 years, whereas low-risk patients had a progression risk of only 1.85%. DISCUSSION: This clinical assay, Esopredict, stratifies future neoplastic progression risk to identify higher-risk patients with BE who can benefit from EET or more frequent surveillance and lower-risk patients who can benefit from reduced surveillance.

BACKGROUND AND AIMS:Liquid nitrogen spray cryotherapy (SCT) is an alternative to radiofrequency ablation (RFA) for eradication of dysplastic Barrett's esophagus (BE). We aimed to assess the safety, efficacy, and durability of SCT in a multicenter U.S. registry. METHODS:This is a multicenter prospective registry of adults with BE treated with truFreeze Spray Cryotherapy (Steris, Mentor, Ohio, USA) (4 community and 11 academic sites, 2013-2022). Complete eradication of intestinal metaplasia (CEIM) and dysplasia (CED) were assessed in BE with dysplasia or intramucosal adenocarcinoma. Kaplan-Meier analysis of CEIM and CED was performed. Hazard ratios for CEIM stratified by baseline risk factors were calculated. RESULTS:Among 138 subjects with low-grade dysplasia (24%), high-grade dysplasia (49%), and intramucosal adenocarcinoma (27%), 34% received prior RFA therapy. Subjects received a median of 2 SCT sessions. Adverse events were uncommon, with 5.5% reporting strictures and 0.7% a perforation. Rates of CEIM and CED, respectively, were 66% and 84% after 2 years and 67% and 92% after 3 years. In RFA-naïve patients, CEIM was 77% and CED was 96% at 3 years. Increasing BE length (per centimeter: adjusted hazard ratio, 0.90; 95% confidence interval, 0.83-0.96) and prior treatment with RFA (adjusted hazard ratio, 0.39; 95% confidence interval, 0.22-0.69) were associated with a lower rate of CEIM. Recurrence occurred in 8.8% (n = 6) at a mean follow-up of 2.5 years after CEIM. CONCLUSION:In this largest reported prospective cohort, liquid nitrogen SCT was safe and effective for the treatment of dysplastic and neoplastic BE. Response was lower in those with prior failed RFA; in that cohort, approximately 50% attained CEIM at 3 years.

Supplementary Tables S1 & S2 from Reprimo Methylation Is a Potential Biomarker of Barrett's-Associated Esophageal Neoplastic Progression

Introduction: Endoscopic liquid nitrogen spray cryotherapy (LNSCT) is an established treatment modality for management of dysplastic Barrett’s esophagus (BE) and esophageal cancer (EC). Placement of an orogastric decompression tube (CDT) is required for active and passive venting of nitrogen gas generated during treatment. Currently available CDTs are limited by size (20 Fr) and soft, flexible material (16 Fr). An enhanced, fluoroscopically visible 16 Fr CDT was developed to maintain luminal patency and rigidity despite a smaller caliber. The aim of this study was to evaluate the performance and safety of this new, FDA-cleared CDT. Methods: This multicenter retrospective on-label case series was approved by central IRB. All adult patients with dysplastic BE or EC who underwent LNSCT using the enhanced CDT in February/March 2023 were included. Primary outcomes included ease of operation/use, rate of intraprocedural adverse events and rate of uninterrupted procedure completion (Figure 1). Results: A total of 28 patients (93% male, mean age 67.4 years) from 16 U.S. medical centers met inclusion criteria (Table 1). The most common indication was EC (20, 71.4%). There were 15 patients (57.7%) with a hiatal hernia and 18 patients (64.3%) with luminal stenosis; 3 (10.7%) had narrowing which prohibited endoscope passage. In 12 cases (42.9%), the endoscopist felt a 20Fr CDT could not have been used (due to luminal stenosis). A standard gastroscope was used for most cases (21, 75%). All patients had intraprocedural abdominal monitoring, with only 1 (3.6%) experiencing mild abdominal distension. All procedures were completed successfully without treatment interruption. Tube integrity was maintained in all patients (100%). Compared to the existing/older 16 Fr CDT, most providers rated insertion of this enhanced CDT as easier (24, 87.5%), with easier endoscope maneuverability (26, 92.9%). Conclusion: To date, LNSCT users have had to choose between ease of per-oral CDT insertion and maintenance of adequate decompression during treatment. These data suggest an enhanced 16 Fr CDT is safe, effective and easier to use than the existing (older) 16 Fr CDT. A smaller caliber CDT is especially useful to facilitate treatment in patients with advanced EC, where tumor bulk and luminal stenosis leads to dysphagia. When used in combination with an ultra-thin (5-6 mm diameter) gastroscope, this enhanced CDT could markedly increase the number of EC patients who can receive palliative LNSCT.Figure 1.: Images Demonstrating LNSCT console, 16Fr Enhanced Cryodecompression Tube and Procedure Images from a Patient with Advanced Esophageal Cancer who Underwent LNSCT Using the Enhanced CDT. 1a: LNSCT console/platform. 1b: Enhanced 16Fr CDT with close up view of fluoroscopically visible distal tip of the tube. 1c: Distal esophagus with advanced, lumen constricting esophageal tumor. 1d and 1e: Esophagus at beginning and end of LNSCT for esophageal tumor palliation, showing the spray catheter (white catheter) and enhanced 16Fr CDT (black arrow) in place. Table 1. - Demographic Data and Study Results Summary All Subjects (n = 28) Age (Years) n 28 Mean (SD) 67.4 (14.97) Median 71.0 Min, Max 30, 91 Gender, n (%) Male 26 (92.9%) Female 2 (7.1%) Race, n (%) African American 3 (10.7%) White 25 (89.3%) Procedure Indication, n (%) Benign 8 (28.6%) Malignant 20 (71.4%) Hiatal Hernia, n (%) Yes 15 (57.7%) No 11 (42.3%) Missing 2 Does Patient Have Luminal Stenosis, n (%) Yes 18 (64.3%) No 10 (35.7%) Allows Passage of Endoscope, n (%) Yes 25 (89.3%) No 3 (10.7%) Type of Gastroscope, n (%) Standard 21 (75.0%) Slim 7 (25.0%) Did Patient Receive Abdominal Monitoring, n (%) Yes 28 (100.0%) Did Patient Experience Abdominal Distension, n (%) Yes 1 (3.6%) No 27 (96.4%) Abdominal Distension Severity, n (%) n 1 Mild 1 (100.0%) Was Treatment Interrupted for Distension, n (%) No 28 (100.0%) Was Tube Integrity Maintained, n (%) Yes 28 (100.0%) Ease of Insertion of Enhanced CDT Compared to Existing CDT, n (%) Easier 24 (85.7%) N/A 1 (3.6%) Same 3 (10.7%) Scope Maneuverability Compared to Current 16Fr CDT, n (%) Easier 26 (92.9%) N/A 1 (3.6%) Same 1 (3.6%) Could a 20Fr CDT Have Been Used for This Case, n (%) Yes 16 (57.1%) No 12 (42.9%)

Supplementary Figure S1 from Reprimo Methylation Is a Potential Biomarker of Barrett's-Associated Esophageal Neoplastic Progression

Introduction: Ischemic colitis in young adults is rare. The incidence in adults less than 40 years is 1.1 per 100,000. It can present with abdominal pain and rectal bleeding after vigorous exercise. In one study, 2% of marathon runners reported blood in stool following races, and 20% of runners had positive fecal occult blood test (FOBT) after marathons.1 The aim of this case report is to heighten awareness of ischemic colitis as possible cause for gastrointestinal bleed in those with recent sports activity. Case Description/Methods: The patient is a 21-year-old man college student with no past medical history who presented with abdominal pain, hematochezia and coffee ground emesis after playing nearly the entire 90 minutes of a NCAA Division 1 soccer match. No prior episodes of hematochezia reported, and he denied use of NSAIDs, performance enhancing medications, or illicit substances. On admission, bradycardia and abdominal discomfort were noted. Labs revealed elevated serum creatinine 2.1 mg/dL consistent with acute kidney injury, elevated creatinine kinase (504 U/L) and lactic acidosis (3.1 mmol/L). Abdominal/pelvic CT angiography and upper GI endoscopy were normal. Colonoscopy revealed ischemic colopathy in the splenic flexure, transverse colon, hepatic flexure and ascending colon (Figure 1A and B). Biopsies from ascending and transverse colon were consistent with ischemic colitis (Figure 1C). He was managed with intravenous fluids, and all symptoms resolved within 24 hours. Discussion: Ischemic colitis in young adults is often associated with hypovolemia and decreased colonic perfusion. Increased sympathetic tone during exercise in hot environment can cause decreased blood flow to colon by 50-80%, thus precipitating ischemic colitis. Areas most affected are the “watershed areas,” areas of colon with the least amount of blood supply, typically at the junction of vascular territories. Management depends on the degree of injury. Non-gangrenous colitis typically resolves spontaneously, whereas antibiotics and surgery should be considered in cases of ischemic colitis with hemodynamic instability with associated full thickness necrosis. This case is an example of exercise induced hypovolemia leading to colonic ischemia. Our patient was managed conservatively with intravenous fluids and recommended for two weeks of cessation from athletics. Reference 1Eichner ER. Gastrointestinal Bleeding in Athletes. Phys Sportsmed. 1989;17(5):128-140.Figure 1.: A and B: Scattered and patchy granular areas in ascending and transverse colon consistent with ischemic colopathy; C: Colonic mucosa with focal ischemic changes.

IMPORTANCE For many types of epithelial malignant neoplasms that are treated with definitive radiotherapy (RT), treatment prolongation and interruptions have an adverse effect on outcomes. OBJECTIVE To analyze the association between RT duration and outcomes in patients with esophageal cancer who were treated with definitive chemoradiotherapy (CRT). DESIGN, SETTING, AND PARTICIPANTS This study was an unplanned, post hoc secondary analysis of 3 prospective, multi-institutional phase 3 randomized clinical trials (Radiation Therapy O ncology Group [RTOG] 8501, RTOG 9405, and RTOG 0436) of the National Cancer Institute-sponsored NRG Oncology (formerly the National Surgical Adjuvant Breast and Bowel Project, RTOG, and Gynecologic Oncology Group). Enrolled patients with nonmetastatic esophageal cancer underwent definitive CRT in the trials between 1986 and 2013, with follow-up occurring through 2014. Data analyses were conducted between March 2022 to February 2023. EXPOSURES Treatment groups in the trials used standard-dose RT (50 Gy) and concurrent chemotherapy. MAIN OUTCOMES AND MEASURES The outcomes were local-regional failure (LRF), distant failure, disease-free survival (DFS), and overall survival (OS). Multivariable models were used to examine the associations between these outcomes and both RT duration and interruptions. Radiotherapy duration was analyzed as a dichotomized variable using an X-Tile software to choose a cut point and its median value as a cut point, as well as a continuous variable. RESULTS The analysis included 509 patients (median [IQR] age, 64 [57-70] years; 418 males [82%]; and 376 White individuals [74%]). The median (IQR) follow-up was 4.01 (2.93-4.92) years for surviving patients. The median cut point of RT duration was 39 days or less in 271 patients (53%) vs more than 39 days in 238 patients (47%), and the X-Tile software cut point was 45 days or less in 446 patients (88%) vs more than 45 days in 63 patients (12%). Radiotherapy interruptions occurred in 207 patients (41%). Female (vs male) sex and other (vs White) race and ethnicity were associated with longer RT duration and RT interruptions. In the multivariable models, RT duration longer than 45 days was associated with inferior DFS (hazard ratio [HR], 1.34; 95% CI, 1.01-1.77; P = .04). The HR for OS was 1.33, but the results were not statistically significant (95% CI, 0.99-1.77; P = .05). Radiotherapy duration longer than 39 days (vs <= 39 days) was associated with a higher risk of LRF (HR, 1.32; 95% CI, 1.06-1.65; P = .01). As a continuous variable, RT duration (per 1 week increase) was associated with DFS failure (HR, 1.14; 95% CI, 1.01-1.28; P = .03). The HR for LRF 1.13, but the result was not statistically significant (95% CI, 0.99-1.28; P = .07). CONCLUSIONS AND RELEVANCE Results of this study indicated that in patients with esophageal cancer receiving definitive CRT, prolonged RT duration was associated with inferior outcomes; female patients and those with other (vs White) race and ethnicity were more likely to have longer RT duration and experience RT interruptions. Radiotherapy interruptions should be minimized to optimize outcomes.

BACKGROUND:The impact of aging on the immune system is unequivocal and results in an altered immune status termed immunosenescence. In humans, the mechanisms of immunosenescence have been examined almost exclusively in blood. However, most immune cells are present in tissue compartments and exhibit differential cell (e.g., memory T cells -TM) subset distributions. Thus, it is crucial to understand immunosenescence in tissues, especially those that are exposed to pathogens (e.g., intestine). Using a human model of oral live attenuated typhoid vaccine, Ty21a, we investigated the effect of aging on terminal ileum (TI) tissue resident memory T (TRM) cells. TRM provide immediate adaptive effector immune responsiveness at the infection site. However, it is unknown whether aging impacts TRM S. Typhi-responsive cells at the site of infection (e.g., TI). Here, we determined the effect of aging on the induction of TI S. Typhi-responsive TRM subsets elicited by Ty21a immunization.RESULTS:We observed that aging impacts the frequencies of TI-lamina propria mononuclear cells (LPMC) TM and TRM in both Ty21a-vaccinated and control groups. In unvaccinated volunteers, the frequencies of LPMC CD103- CD4+ TRM displayed a positive correlation with age whilst the CD4/CD8 ratio in LPMC displayed a negative correlation with age. We observed that elderly volunteers have weaker S. Typhi-specific mucosal immune responses following Ty21a immunization compared to adults. For example, CD103+ CD4+ TRM showed reduced IL-17A production, while CD103- CD4+ TRM exhibited lower levels of IL-17A and IL-2 in the elderly than in adults following Ty21a immunization. Similar results were observed in LPMC CD8+ TRM and CD103- CD8+ T cell subsets. A comparison of multifunctional (MF) profiles of both CD4+ and CD8+ TRM subsets between elderly and adults also showed significant differences in the quality and quantity of elicited single (S) and MF responses.CONCLUSIONS:Aging influences tissue resident TM S. Typhi-specific responses in the terminal ileum following oral Ty21a-immunization. This study is the first to provide insights in the generation of local vaccine-specific responses in the elderly population and highlights the importance of evaluating tissue immune responses in the context of infection and aging.TRIAL REGISTRATION:This study was approved by the Institutional Review Board and registered on ClinicalTrials.gov (identifier NCT03970304 , Registered 29 May 2019 - Retrospectively registered).

BACKGROUND:Over 6 million esophagogastroduodenoscopy (EGD) procedures are performed in the United States each year. Patients having anesthesia for advanced EGD procedures, such as interventional procedures, are at high risk for hypoxemia. METHODS:Our primary study aim was to evaluate whether high-flow nasal cannula (HFNC) oxygen reduces the incidence of hypoxemia during anesthesia for advanced EGD. Secondarily, we studied whether HFNC oxygen reduces hypercarbia or hypotension. After obtaining written informed consent, adults having anesthesia for advanced EGD, expected to last longer than 15 minutes, were randomly assigned to receive HFNC oxygen or standard nasal cannula (SNC) oxygen. The primary outcome was occurrence of one or more hypoxemia events during anesthesia, defined by arterial oxygen saturation <92% for at least 15 consecutive seconds. Secondary outcomes were occurrence of one or more hypercarbia or hypotension events. A hypercarbia event was defined by a transcutaneous CO2 measurement 20 mm Hg or more above baseline, and a hypotension event was defined by a mean arterial blood pressure measurement 25% or more below baseline. RESULTS:Two hundred seventy-one adult patients were enrolled and randomized, and 262 patients completed study procedures. Eight randomized patients did not complete study procedures due to changes in their anesthesia or endoscopy plan. One patient was excluded from analysis because their procedure was aborted after 1 minute. Patients who received HFNC oxygen (N = 132) had a significantly lower incidence of hypoxemia than those who received SNC oxygen (N = 130; 21.2% vs 33.1%; hazard ratio [HR] = 0.59 [95% confidence interval {CI}, 0.36-0.95]; P = .03). There was no difference in the incidence of hypercarbia or hypotension between the groups. The HR for hypercarbia with HFNC oxygen was 1.29 (95% CI, 0.89-1.88; P = .17), and the HR for hypotension was 1.25 (95% CI, 0.86-1.82; P = .25). CONCLUSIONS:HFNC oxygen reduces the incidence of hypoxemia during anesthesia for advanced EGD and may offer an opportunity to enhance patient safety during these procedures.

MicroRNA (miR)−141‐3p, which functions as an oncogene in multiple malignancies, has been shown to be highly overexpressed in esophageal cancer cells in our previous work. miR‐141‐3p is predicted to bind the messenger RNA (mRNA) of tuberous sclerosis complex 1 (TSC1), a tumor suppressor, with high affinity. In this study, we investigated the expression and functional interaction between miR‐141‐3p and TSC1 in esophageal cancer cells. Experiments were conducted in four esophageal cancer lines and in tumor cells isolated from human esophageal cancer specimens by laser capture microdissection. miR‐141‐3p expression was measured by real time and droplet digital PCR. Biotinylated RNA pull‐down and luciferase reporter assays were used to assess binding. miR‐141‐3p function was tested by assessing proliferation, migration, invasion, and induction of autophagy following its silencing. We found that miR‐141‐3p levels were increased in TE7, OE33, and TE10 esophageal cancer cells compared to FLO‐1 cells, with similar heterogeneity observed in human esophageal cancer specimens. Silencing of miR‐141‐3p led to increased TSC1 protein expression in these cells and was associated with increased TSC1 translation. Binding studies reveal that miR‐141‐3p binds to each of the predicted binding sites in the 3′‐untranslated region of TSC1 mRNA. Following miR‐141‐3p silencing, TE7, OE33, and TE10 cells exhibited decreased proliferation, migration, and invasion, as well as enhanced autophagy. Importantly, these phenotypic effects were replicated by overexpression of TSC1 alone in these cells. Our results indicate that miR‐141‐3p functions in an oncogenic capacity in a subset of esophageal cancer cells, in part by suppressing TSC1 expression.

Dysphagia is a common presenting symptom in esophageal cancer. Poor nutrition and diminished quality of life are often the result. Traditional options to manage dysphagia – esophageal stents, radiation, chemotherapy, and dilation – all have limitations. Liquid nitrogen spray cryotherapy (truFreeze, CSA Medical, Inc., Lexington, Massachusetts, United States) has been used successfully to treat inoperable early-stage esophageal cancer and to palliate dysphagia in locally advanced tumors [1]. This non-contact method uses liquid nitrogen at –196° to effectively freeze and destroy esophageal tumors with excellent tolerability and safety profile.

Abstract Background Salmonella enterica serovar Typhi (S. Typhi) is a highly invasive bacterium that infects the human intestinal mucosa and causes ~ 11.9–20.6 million infections and ~ 130,000–223,000 deaths annually worldwide. Oral typhoid vaccine Ty21a confers a moderate level of long-lived protection (5–7 years) in the field. New and improved vaccines against enteric pathogens are needed but their development is hindered by a lack of the immunological correlates of protection especially at the site of infection. Tissue resident memory T (TRM) cells provide immediate adaptive effector immune responsiveness at the infection site. However, the mechanism(s) by which S. Typhi induces TRM in the intestinal mucosa are unknown. Here, we focus on the induction of S. Typhi-specific CD4+TRM subsets by Ty21a in the human terminal ileum lamina propria and epithelial compartments. Methods Terminal ileum biopsies were obtained from consenting volunteers undergoing routine colonoscopy who were either immunized orally with 4 doses of Ty21a or not. Isolated lamina propria mononuclear cells (LPMC) and intraepithelial lymphocytes (IEL) CD4+TRM immune responses were determined using either S. Typhi-infected or non-infected autologous EBV-B cell lines as stimulator cells. T-CMI was assessed by the production of 4 cytokines [interferon (IFN)γ, interleukin (IL)-2, IL-17A and tumor necrosis factor (TNF)α] in 36 volunteers (18 vaccinees and 18 controls volunteers). Results Although the frequencies of LPMC CD103+ CD4+TRM were significant decreased, both CD103+ and CD103− CD4+TRM subsets spontaneously produced significantly higher levels of cytokines (IFNγ and IL-17A) following Ty21a-immunization. Importantly, we observed significant increases in S. Typhi-specific LPMC CD103+ CD4+TRM (IFNγ and IL-17A) and CD103− CD4+TRM (IL-2 and IL-17A) responses following Ty21a-immunization. Further, differences in S. Typhi-specific responses between these two CD4+TRM subsets were observed following multifunctional analysis. In addition, we determined the effect of Ty21a-immunization on IEL and observed significant changes in the frequencies of IEL CD103+ (decrease) and CD103− CD4+TRM (increase) following immunization. Finally, we observed that IEL CD103− CD4+TRM, but not CD103+ CD4+TRM, produced increased cytokines (IFNγ, TNFα and IL-17A) to S. Typhi-specific stimulation following Ty21a-immunization. Conclusions Oral Ty21a-immunization elicits distinct compartment specific immune responses in CD4+TRM (CD103+ and CD103−) subsets. This study provides novel insights in the generation of local vaccine-specific responses. Trial registration This study was approved by the Institutional Review Board and registered on ClinicalTrials.gov (identifier NCT03970304, Registered 29 May 2019—Retrospectively registered, http://www.ClinicalTrials.gov/NCT03970304 )

Liquid nitrogen spray cryotherapy (SCT) has been shown to be safe and effective in achieving complete eradication of intestinal metaplasia (CEIM) in Barrett's esophagus (BE). However, rates of recurrence after successful CEIM in registry patients are incompletely described.