Comprehensive Assessment of Esophageal Disorders Associated with Hiatus Hernia: Insights from Big Data Analysis.

Hiatus hernia (HH) is a prevalent endoscopic finding in clinical practice, frequently co-occurring with esophageal disorders, yet the prevalence and degree of association remain uncertain. We aim to investigate HH's frequency and its suspected association with esophageal disorders. We reviewed endoscopic reports of over 75,000 consecutive patients who underwent gastroscopy over 12 years in two referral centers. HH was endoscopically diagnosed. We derived data on clinical presentation and a comprehensive assessment of benign and malignant esophageal pathologies. We performed multiple regression models to identify esophageal sequela associated with HH. The overall frequency of HH was (16.8%); the majority (89.5%) had small HHs (<3 cm). Female predominance was documented in HH patients, who were significantly older than controls (61.1±16.5 vs. 52.7±20.0; P < 0.001). The outcome analysis of esophageal pathology revealed an independent association between HH, regardless of its size, and erosive reflux esophagitis (25.7% vs. 6.2%; OR = 3.8; P < 0.001) and Barrett's esophagus (3.8% vs. 0.7%; OR = 4.7, P < 0.001). Furthermore, following rigorous age and sex matching, in conjunction with additional multivariable analyses, large HHs were associated with higher rates of benign esophageal strictures (3.6% vs. 0.3%; P < 0.001), Mallory Weiss syndrome (3.6% vs. 2.1%; P = 0.01), and incidents of food impactions (0.9% vs. 0.2%; P = 0.014). In contrast, a lower rate of achalasia was noted among this cohort (0.55% vs. 0%; P = 0.046). Besides reflux-related esophageal disorders, we outlined an association with multiple benign esophageal disorders, particularly in patients with large HHs.

Esclerodermia y alteraciones esofágicas documentadas por manometría / Scleroderma and Esophageal Alterations Documented by Manometry

Introducción: Las manifestaciones gastrointestinales y en especial la disfunción esofágica son frecuentes en pacientes con diagnóstico de esclerosis sistémica. Objetivos: Determinar los hallazgos manométricos en el esófago de pacientes con esclerosis sistémica. Métodos: Se realizó un estudio descriptivo de corte transversal, en 86 pacientes con diagnóstico de esclerosis sistémica que fueron atendidos en el Servicio de Reumatología del Hospital Hermanos Ameijeiras, en el período comprendido de enero de 2020 a diciembre de 2021. Resultados: La edad media fue de 49,5 ± 15,3 años, (94,3 por ciento) en el sexo femenino. El (90,7 por ciento) tenía trastornos de la motilidad esofágica, principalmente los trastornos mayores (58,1por ciento) y el esfínter esofágico corto (62,8 por ciento). La presencia de síntomas como la regurgitación, la pirosis y la disfagia se relacionaron de forma significativa en la mayoría de los parámetros manométricos. De igual forma, el tiempo de evolución de la enfermedad (10,1 ± 9,1 frente a 5,9 ± 5,9 años), el fenómeno de Raynaud (93,9 por ciento frente a 25,0 por ciento) y la esclerosis sistémica difusa (96,2 por ciento frente a 82,4 por ciento) fueron significativamente mayores en pacientes con trastornos de la motilidad esofágica. La edad y el sexo no mostraron una asociación significativa con las alteraciones manométricas. Conclusiones: Se concluye que los pacientes con esclerosis sistémica difusa, fenómeno de Raynaud, a partir de la presencia de los síntomas y de la evolución de la enfermedad tienen una elevada probabilidad de padecer trastornos de la motilidad esofágica(AU)

Introduction: Gastrointestinal manifestations, and especially esophageal dysfunction, are common in patients diagnosed with systemic sclerosis. Objectives: To determine the manometric findings in the esophagus of patients with systemic sclerosis. Methods: A descriptive cross-sectional study was carried out on 86 patients with a diagnosis of systemic sclerosis who were treated in the Rheumatology Service of Hermanos Ameijeiras Hospital from January 2020 to December 2021. Results: The mean age was 49.5 ± 15.3 years, (94.3percent) in females. 90.7percent had esophageal motility disorders, mainly major disorders (58.1percent) and 62.8percent had short esophageal sphincter. The presence of symptoms such as regurgitation, heartburn and dysphagia were significantly related to most manometric parameters. Similarly, the duration of the disease (10.1 ± 9.1 versus 5.9 ± 5.9 years), Raynaud's phenomenon (93.9percent versus 25.0percent) and sclerosis diffuse systemic (96.2percent vs. 82.4percent) were significantly higher in patients with esophageal motility disorders. Age and sex did not show significant association with manometric alterations. Conclusions: It is concluded that patients with diffuse systemic sclerosis, Raynaud's phenomenon, based on the presence of symptoms, and the evolution of the disease, have high probability of suffering from esophageal motility disorders(AU)

Esophageal Stricture: An Uncommon Complication of Cervical Inlet Patch.

Esophageal heterotopic gastric mucosal patches (HGMP), also known as cervical inlet patches (CIP), is a rare but underdiagnosed condition characterized by the presence of salmon-colored, velvety mucosa located in the proximal esophagus, distal to the upper esophageal sphincter. The incidence of CIP ranges from 3% to 10% in adults, and its endoscopic appearance is characterized by a flat or slightly raised salmon-colored patch. In this case, we report a 78-year-old man who presented with symptoms of laryngopharyngeal reflux and dysphagia. An esophagogastroduodenoscopy showed a flat area of salmon-colored patch between 17 and 20 cm from the incisors, suggestive of a CIP complicated by stricture. The biopsy results showed an oxyntic-type mucosa lined with columnar cells consistent with an inlet patch. Esophageal dilation was done with a savory dilator with no resistance at 18 mm. The patient was placed on maintenance acid suppression therapy with proton-pump inhibitors and reported complete resolution of symptoms at the 1-month follow-up.

Heterotopic Gastric Mucosa in the Proximal Esophagus: Prospective Study and Systematic Review on Relationships with Endoscopic Findings and Clinical Data.

Cervical inlet patches (CIP) are common endoscopic findings with uncertain pathogenesis and clinical significance. We aimed to perform a systematic review and prospective study of clinical data and endoscopic findings related to CIP. It was a prospective single-center study conducted between 10/01/2017 and 9/01/2018. Forty patients with histopathologically confirmed CIP were compared with 222 individuals in the reference group. The systematic review was executed in accordance with the PRISMA guideline. Alcohol consumption tended to be higher among patients with CIP (3.0 ± 4.6 vs. 1.9 ± 5.0 standard drinks/week CIP patients and reference group, respectively; p < 0.001). Dysphagia was more frequent among patients with CIP (25% vs. 1.4%, CIP patients and reference group, respectively; p < 0.001), and sore throat and hoarseness were less frequent in patients with CIP (17.5% vs. 26.6% CIP patients and reference group, respectively; p < 0.01). In the multivariate regression analysis, the only risk factor of CIP occurrence was dysphagia (OR 21.9, 95%CI 4.9-98.6; p < 0.001). Sore throat and hoarseness were a reverse-risk factor of CIP diagnosis (OR 0.3, 95%CI 0.1-0.93; p = 0.04). Clinical data and coexisting endoscopic findings were not related to CIP. In the presented study, dysphagia was related to CIP occurrence, and sore throat and hoarseness tended to be less frequent among patients with CIP.

The true prevalence of cervical inlet patch in a specific center dealing with esophageal diseases.

OBJECTIVE: Cervical Inlet Patch (CIP) is an interesting entity that is little known and often neglected by endoscopists. It has always been reported as less than expected. In this article, for the first time in the literature, we want to measure the true prevalence of CIP in a center dealing with specific esophageal diseases. PATIENTS AND METHODS: From October 2020 to October 2021, a total of 283 patients, aged 15-95 years, with mainly dyspeptic and reflux-like complaints were included in this study. All endoscopic procedures were performed carefully by a single endoscopist. Patients were examined for any possible presence of CIP, with adequate sedation and time. RESULTS: The prevalence of CIP, which was the primary aim of our study, was detected at a rate of 14.8%. Most CIP was observed as a single lesion (73.8%), and many of them (45.2%) were larger than 10 mm. Plenty of patients had upper endoscopy due to dyspeptic complaints, but only 2.5% of them presented with a preliminary diagnosis of laryngeal reflux. CONCLUSIONS: The true CIP prevalence is higher than reported before. Our result is the highest prevalence rate of CIP was detected in Turkey. In this regard, data coming from centers dealing with specific esophageal diseases may be more reliable and true.

Esophageal Eosinophilia and Eosinophilic Esophagitis in Celiac Children: A Ten Year Prospective Observational Study.

The association between eosinophilic esophagitis and celiac disease is still controversial and its prevalence is highly variable. We aimed to investigate the prevalence of esophageal eosinophilia and eosinophilic esophagitis in a large group of children with celiac disease, prospectively followed over 11 years. METHODS: Prospective observational study performed between 2008 and 2019. Celiac disease diagnosis was based on ESPGHAN criteria. At least four esophageal biopsies were sampled in patients who underwent endoscopy. The presence of at least 15 eosinophils/HPF on esophageal biopsies was considered suggestive of esophageal eosinophilia; at the same time, eosinophilic esophagitis was diagnosed according to the International Consensus Diagnostic Criteria for Eosinophilic Esophagitis. RESULTS: A total of 465 children (M 42% mean age 7.1 years (range: 1-16)) were diagnosed with celiac disease. Three hundred and seventy patients underwent endoscopy, and esophageal biopsies were available in 313. The prevalence of esophageal eosinophilia in children with celiac disease was 1.6% (95% CI: 0.54-2.9%). Only one child was diagnosed as eosinophilic esophagitis; we calculated a prevalence of 0.3% (95% CI: 0.2-0.5%). The odds ratio for an association between eosinophilic esophagitis and celiac disease was at least 6.5 times higher (95% CI: 0.89-47.7%; p = 0.06) than in the general population. CONCLUSION: The finding of an increased number of eosinophils (>15/HPF) in celiac patients does not have a clinical implication or warrant intervention, and therefore we do not recommend routine esophageal biopsies unless clinically indicated.

[Esophageal Lichen Planus - an Underdiagnosed Disease]. / Der Lichen planus des Ösophagus ­ Eine unterschätzte Erkrankung.

An involvement of the esophagus in patients with lichen planus was described for the first time in 1982. Ever since, it has been seen as a rarity. However, studies over the last 10 years have shown a higher prevalence than expected. It may even be supposed that esophageal lichen planus (ELP) is more common than eosinophilic esophagitis. ELP mostly affects middle-aged women. The principal symptom is dysphagia. Endoscopically, ELP is characterized by denudation and tearing of the mucosa, trachealization and hyperkeratosis and esophageal stenosis may occur in patients with long courses of the disease. Histologic findings including mucosal detachment, T-lymphocytic infiltrate, intraepithelial apoptosis (civatte bodies) and dyskeratosis are crucial. Direct immunofluorescence shows fibrinogen deposits along the basement membrane zone. So far, there is no well-established therapy but a treatment with topic steroids is effective in 2/3 of the patients. Common therapy of lichen planus of the skin seems to be ineffective for treatment of ELP. Symptomatic esophageal stenosis should be endoscopically dilated. ELP joins the group of "new" immunologic diseases of the esophagus.

Esophageal disease among childhood cancer survivors-A report from the Childhood Cancer Survivors Study.

There is limited information addressing the occurrence of esophageal strictures among the growing population of survivors of childhood cancer. Using the Childhood Cancer Survivor Study, we analyzed data from 17,121 5-year survivors and 3400 siblings to determine the prevalence and risk factors for esophageal strictures. Prevalence among survivors was 2.0% (95% confidence interval [CI]: 1.8-2.2%), representing a 7.6-fold increased risk compared to siblings. Factors significantly associated with risk of esophageal stricture included diagnosis of Hodgkin lymphoma, greater chest radiation dose, younger age at cancer diagnosis, platinum chemotherapy, and hematopoietic stem cell transplantation. While uncommon, survivors are at risk for therapy-related esophageal strictures.

Esophageal Epidermoid Metaplasia: Clinical Characteristics and Risk of Esophageal Squamous Neoplasia.

INTRODUCTION: Esophageal epidermoid metaplasia (EEM) is a rare disease. METHODS: Patients with EEM diagnosed between 2014 and 2020 were reviewed. RESULTS: Forty EEM cases were identified. EEM occurred in 9 (23%) patients before, concordant, or after esophageal squamous cell carcinoma (ESCC). EEM was associated with previous esophageal lichen planus in 5 patients, Barrett's esophagus 7, and esophageal adenocarcinoma 1. EEM was focal in 28 (70%) or diffuse in 12 (30%) and not detected in 45% on recent previous endoscopy. DISCUSSION: EEM is a premalignant underrecognized condition associated with multiple conditions. Close follow-up or endoscopic treatment may be warranted because of its ESCC association.

Anticholinergic, anti-depressant and other medication use is associated with clinically relevant oesophageal manometric abnormalities.

BACKGROUND: Medications can affect gastrointestinal tract motility. However, their effects on oesophageal motility in particular are often not as widely known or may be underestimated. AIM: To review the effect of existing medication use on high-resolution oesophageal manometry (HRM) in a 'real-world' setting. METHODS: Adult patients with upper gut symptoms and normal endoscopy or imaging who had HRM over a 22-month period were analysed. Achalasia and major disorders of peristalsis were excluded. All medications taken within 24 hours of the procedure were prospectively recorded and compared with HRM results, controlling for age, gender and proton pump inhibitor use. RESULTS: A total of 502 patients (323 female, mean age 51) were recruited. Of these, 41.2% had normal oesophageal HRM, while 41.4% had ineffective oesophageal motility (IOM) and 7.6% had oesophagogastric junction outflow obstruction (OGJOO). Serotonin/norepinephrine reuptake inhibitors (SNRI) and opioids were associated with significantly higher resting lower oesophageal sphincter pressure. Benzodiazepines and opioids were associated with elevated integrated relaxation pressure. SNRI and inhaled beta-agonists were associated with increased distal contractile index, whereas calcium channel blockers were associated with a lower distal contractile index. Odds ratio of being on anticholinergics was higher in IOM patients vs normal (3.6, CI 1.2-10.8). Odds ratio for anticholinergics, inhaled beta-agonists, anticonvulsants, SNRIs and opioids (trend) were all > 3 for OGJOO patients vs normal. CONCLUSION: Many medication classes are associated with abnormal HRM variables and diagnoses such as OGJOO and IOM; some of these associations are probably causal. These possible links should be taken into consideration during manometry interpretation.

Age at Initiation and Frequency of Screening to Prevent Esophageal Squamous Cell Carcinoma in High-risk Regions: an Economic Evaluation.

The aim of this study was to identify the economic screening strategies for esophageal squamous cell carcinoma (ESCC) in high-risk regions. We used a validated ESCC health policy model for comparing different screening strategies for ESCC. Strategies varied in terms of age at initiation and frequency of screening. Model inputs were derived from parameter calibration and published literature. We estimated the effects of each strategy on the incidence of ESCC, costs, quality-adjusted life-year (QALY), and incremental cost-effectiveness ratios (ICERs). Compared with no screening, all competing screening strategies decreased the incidence of ESCC from 0.35% to 72.8%, and augmented the number of QALYs (0.002-0.086 QALYs per person) over a lifetime horizon. The screening strategies initiating at 40 years of age and repeated every 1-3 years, which gained over 70% of probabilities that was preferred in probabilistic sensitivity analysis at a $1,151/QALY willingness-to-pay threshold. Results were sensitive to the parameters related to the risks of developing basal cell hyperplasia/mild dysplasia. Endoscopy screening initiating at 40 years of age and repeated every 1-3 years could substantially reduce the disease burden and is cost-effective for the general population in high-risk regions.

Three cases of an unusual cause of haematemesis: black oesophagus.

Black oesophagus, also termed acute oesophageal necrosis or Gurvits syndrome, is an uncommon but well-characterised entity predominantly involving the lower oesophagus. Co-morbidity-such as diabetes mellitus, hypertension, chronic liver or kidney or pulmonary disease-predisposes to this condition. On endoscopy, it appears as a diffuse, circumferential, black discolouration. Though poorly understood, tissue hypoperfusion appears central to its pathogenesis. Tackling the underlying predisposing co-morbidity and supportive management are the mainstay of therapy. Despite early diagnosis and prompt treatment, the outcome may be unfavourable and is related to the underlying aetiology. We report a case series of three patients of acute oesophageal necrosis who presented to us with symptoms of acute upper gastrointestinal bleeding and improved with conservative management.

Esophagogastroduodenoscopy and Esophageal Involvement in Patients with Pemphigus Vulgaris.

Pemphigus vulgaris (PV) is a rare autoimmune blistering disease involving the skin and mucous membranes. The prevalence of esophageal involvement remains uncertain. The aim of our study was to determine the frequency of esophageal involvement in patients with PV. This is a single-center electronic database retrospective review of patients with a diagnosis of PV. Data abstracted included demographics, disease characteristics (biopsy results, symptoms, areas affected, treatments), and esophagogastroduodenoscopy (EGD) reports. Of the 111 patients that met eligibility criteria, only 22 (19.8%) underwent EGD. Demographic data were similar except those who underwent EGD were more likely to be female (77.3% vs. 51.7%, p = 0.05) and have hypertension (50.0% vs. 24.7%, p = 0.04). Esophageal symptoms were common in both groups; however, those experiencing dysphagia were more likely to undergo EGD (50.0% vs. 20.2%, p = 0.007). Those who underwent EGD had more refractory disease (≥ 3 treatment modalities: 100% vs. 58.4%, p < 0.001), but did not differ in areas affected. Of those who underwent EGD, only 4 (18.2%) had esophageal abnormalities either prior to PV diagnosis (1) or during a disease flare (3). Those having a flare were more likely to experience odynophagia (69.2%) or weight loss (61.5%), p = 0.02 and p = 0.05, respectively. While esophageal symptoms were common in our cohort of PV patients, a minority of patients underwent EGD, and the vast majority of those were unremarkable. This suggests that while esophageal symptoms are common in PV, permanent esophageal injury is more rare.

Oral Health-Related Quality of Life After Gastric Bypass Surgery.

OBJECTIVE: The aim was to examine how individuals treated for obesity with gastric bypass (GBP) surgery perceived their oral health and oral health-related quality of life (OHRQoL). METHOD: All individuals in one Swedish region who had undergone GBP surgery (n = 1182) were sent a postal questionnaire 2 years after surgery. The questionnaire comprised items on sociodemographics, oral symptoms and the Oral Health Impact Profile-49 to assess the OHRQoL. RESULTS: The mean age was 47.6 years with 75% females, response rate 55.3%. The self-perceived oral health was rated low by 45% of the respondents. Gender differences were seen, for instance, regarding hypersensitive teeth (men 18.8%, women 30.8%, p = 0.003). Nine out of ten reported at least one oral impact experienced sometimes, fairly or very often, according to the Oral Health Impact Profile-49 (OHIP-49). The mean additive OHIP-49 score was 30.3 (SD 36.1). The associations between self-reported oral health and OHRQoL were consistent throughout. Tooth hypersensitivity generated an OR of 2.28 (95% CI 2.28-8.46) of having ≥ 2 impacts on OHRQoL. CONCLUSION: A large proportion of individuals having undergone GBP surgery reported problems with their oral health and impacts on their OHRQoL, indicating a need for medical and dental staff-surgeons and general practitioners as well as other health professionals-to offer oral health promotion and prevention measures.

Clinical, Endoscopic, and Histologic Findings at the Distal Esophagus and Stomach Before and Late (10.5 Years) After Laparoscopic Sleeve Gastrectomy: Results of a Prospective Study with 93% Follow-Up.

OBJECTIVE: Perform a prospective study based on sequential clinical, endoscopic, and histologic evaluations of the foregut late after laparoscopic sleeve gastrectomy (LSG) in obese patients. After LSG, several studies have suggested an increase in the incidence of clinical gastroesophageal reflux (GERD) while others have reported an improvement but based mainly on clinical questionnaires. METHODS: Prospective study of 104 consecutive patients submitted to LSG. Several postoperative endoscopic and histologic evaluations of the esophagogastric junction (EGJ) and the gastric tube (GT) were performed and correlated with symptomatic findings. RESULTS: According to clinical preoperative findings, patients were divided into non-refluxers (Group I) and refluxers (Group II). Seven patients were unreachable, leaving 97 (93%) for late evaluation. Among Group I, 58.5% developed de novo GERD, while in Group II just 13.6% showed the disappearance of them. Endoscopic evaluations showed progressive deterioration of the EGJ in Group I, with the development of erosive esophagitis (EE), hiatal hernia (HH), and dilated cardia in a large proportion of them. In the GT, the presence of bile was seen in 40%, and an open immobile pylorus was detected in 82%. Short-segment Barrett's esophagus (BE) appeared in 4%. CONCLUSIONS: Patients submitted to LSG showed a significant and progressive increase in the presence of "de novo" GERD. Also, an increased duodenogastric reflux was seen through an open and immobile pylorus. Therefore, based on these results, it seems like LSG is a "pro-reflux" surgical procedure, which should be continuously evaluated late after surgery.

Pattern of oesophageal diseases in Madinah region, Saudi Arabia: An 11 years experience.

The oesophagus can be a site for a variety of lesions including inflammatory disorders, infections, mechanical conditions, toxic and physical injuries, vascular disorders and neoplastic conditions. hence the oesophageal diseases have a wide spectrum of pathological features. An understanding of histopathological details of oesophageal diseases is essential for their accurate diagnosis and management. The main objective of our study was to provide a comprehensive audit of oesophageal diseases in the province of Madinah in Saudi Arabia. From January 2006 to December 2017, were viewed the histopathological patterns of oesophageal lesions in patients at a tertiary care referral hospital who were diagnosed with oesophageal disease after upper gastroendoscopy. Of the 201 patients, 144 (71.6%) cases were found to be non-neoplastic and 57 (28.4%) cases were neoplastic. Our findings were comparable with earlier studies that helped establish a baseline of an oesophageal disease pattern, on the basis of histopathological examinations.

Esophageal symptoms and their lack of association with high-resolution manometry in systemic sclerosis patients / Falta de asociación de síntomas esofágicos con la manometría de alta resolución en pacientes con esclerosis sistémica

Background: The esophageal involvement in systemic sclerosis (SSc) causes impact in the morbidity and mortality. High resolution manometry assesses esophageal involvement. Our aim was to categorize esophageal motor disorder in patients with SSc by HRM. Methods: We carried out an observational, descriptive and cross-sectional study. All patients underwent HRM as well as semi-structured interviews to assess frequency and severity of upper GI symptoms. Patients also completed the gastroesophageal reflux questionnaire (Carlsson-Dent). Results: We included 19 patients with SSc, 1 with morphea, and 1 with scleroderma sine scleroderma. Dysphagia and heartburn were the most frequent symptoms (61% each). We found an abnormal HRM in 15 (71.4%) patients. We found no statistically significant association between clinical or demographic variables and an abnormal HRM, or between any upper GI symptom and HRM findings. Conclusion: We observed a high prevalence of esophageal symptoms and of HRM abnormalities. However, there was no clear association between symptomatology and HRM findings. HRM does not seem to accurately predict upper GI symptomatology

Antecedentes: La afectación esofágica en la esclerosis sistémica causa impacto en la morbimortalidad. La manometría de alta resolución evalúa la afectación esofágica. Nuestro objetivo fue categorizar el trastorno motor esofágico en pacientes con esclerosis sistémica por HRM. Métodos: Se realizó un estudio observacional, descriptivo y transversal. Todos los pacientes se sometieron a HRM, así como a entrevistas semiestructuradas para evaluar la frecuencia y la gravedad de los síntomas gastrointestinales. Los pacientes también completaron el cuestionario de reflujo gastroesofágico (Carlsson-Dent). Resultados: Se incluyeron 19 pacientes con esclerosis sistémica, uno con morfea y uno con esclerodermia seno esclerodermia. La disfagia y la pirosis fueron los síntomas más frecuentes (un 61% cada uno). Encontramos una HRM anormal en 15 (71,4%) pacientes. No se halló ninguna asociación estadísticamente significativa entre las variables clínicas o demográficas y una HRM anormal, o entre cualquier síntoma GI superior y los hallazgos de HRM. Conclusión: Se observó una alta prevalencia de síntomas esofágicos y de anomalías de la HRM. Sin embargo, no hubo asociación clara entre la sintomatología y los hallazgos de HRM. La HRM no parece predecir con precisión la sintomatología gastrointestinal

Time-to-isolation-guided cryoballoon ablation reduces oesophageal and mediastinal alterations detected by endoscopic ultrasound: results of the MADE-PVI trial.

AIMS: Cryoballoon ablation is safe and efficient for achieving pulmonary vein isolation (PVI) in atrial fibrillation. Structural oesophago-mediastinal lesions, which seem to be associated with an increased risk of the lethal complication of an atrio-oesophageal fistula, have been described. MADE-PVI (Mediastino-oesophageal Alterations Detected by Endosonography after PVI) aimed at evaluating safety of cryoballoon PVI in relation to two different freeze protocols. As time-to-isolation-(TTI)-guided protocol has been reported to be as effective as conventional 'two freeze protocol', we hypothesized a TTI-guided protocol causes less oesophago-mediastinal lesions. METHODS AND RESULTS: Seventy consecutive patients were scheduled for cryoballoon (2nd generation) PVI employing either a conventional protocol (n = 35: 2 × 180 s per vein) or a TTI-guided approach (n = 35: TTI + 120 s per vein or 1 × 180 s in case TTI could not be measured). Oesophagogastroduodenoscopy and endoscopic ultrasound, assessing oesophago-mediastinal alterations (e.g. ulceration, oedema) were performed blinded prior and post-ablation. Post-interventional mediastinal oedematous alterations were detected in 70% with a mean diameter of 14 mm (±0.9 mm), while only 15% revealed large mediastinal oedema >20 mm. Oesophageal lesions due to PVI occurred in 5%. Freeze protocols had a distinct impact on oesophago-mediastinal alterations as mean diameter and frequency of large oedema were significantly increased in patients after conventional protocol PVI (17 mm vs. 11 mm; 26% vs. 6%). Furthermore, every oesophageal lesion was detected in patients with conventional protocol (9%). No major complication occurred in either group. CONCLUSION: The present prospective study demonstrates a significant impact of freeze protocol on oesophago-mediastinal alterations. A TTI-guided protocol reduces mediastino-oesophageal lesions and may reduce short- and long-term complications of cryoballoon PVI.