[Gender medicine in diseases of the upper gastrointestinal tract]. / Gendermedizin bei Erkrankungen des oberen Gastrointestinaltrakts.

Benign and malignant diseases of the upper gastrointestinal tract show gender-specific differences. The frequent gastroesophageal reflux disease is a prime example: men have an erosive reflux disease more often than women and are also younger at the time of onset. The rate of progression to a metaplastic Barrett's esophagus is also higher in men. In the case of achalasia, there are indications that surgical treatment by laparoscopic Heller's myotomy and semifundoplication 180° according to Dor leads to a markedly better improvement in the symptoms in women compared to men, although they showed a more pronounced dilation of the tubular esophagus. The female hormone status influences the localization and histopathology of adenocarcinoma of the esophagogastric junction and gastric carcinoma. Premenopausal and postmenopausal carcinomas differ significantly in women. In addition, high microsatellite instability (MSI high) is more frequent in women and is associated with a generally significantly better prognosis. The MSI high gastric carcinomas of women show better survival than MSI high carcinomas of men. The future inclusion of gender-specific aspects in studies of the upper gastrointestinal tract is desirable in order to generate adequate data and to enable differentiated treatment stratification in the future.

POEM for non-achalasia spastic oesophageal motility disorders.

Non-achalasia oesophageal motility disorders (NAOMD) represent a heterogeneous group of rare diseases, including oesophagogastric junction outflow obstruction, distal oesophageal spasm, and hypercontractile oesophagus. Despite the differing aetiological, manometric and pathophysiological characteristics, these disorders are unified by similar clinical presentation, including dysphagia and chest pain. The management of these disorders remain a challenge for the clinician. Pharmacotherapy, botulinum toxin injection, endoscopic dilation, and laparoscopic Heller myotomy have been employed, with limited efficacy in the majority of patients. Currently, there are no controlled studies in literature that suggest which is the best management of these diseases. Since its introduction in clinical practice, PerOral Endoscopic Myotomy (POEM) has emerged as a very promising, minimally invasive and effective treatment for oesophageal achalasia. No longer after the first uses, POEM has been successfully used also for the management of selected patients with NAOMD, However, currently available data are limited by small study sample sizes and short-term follow-up.

Per oral endoscopic myotomy for achalasia.

Achalasia, characterized by impaired lower esophageal sphincter (LES) relaxation and failed peristalsis, stands out as the most widely recognized primary esophageal motility disorder. It manifests with dysphagia to solid and liquid foods, chest pain, regurgitation, and weight loss, leading to significant morbidity and healthcare burden. Traditionally, surgical Heller myotomy and pneumatic dilation were the primary therapeutic approaches for achalasia. However, in 2009, Inoue and colleagues introduced a groundbreaking endoscopic technique called peroral endoscopic myotomy (POEM), revolutionizing the management of this condition. This review aims to comprehensively examine the recent advancements in the POEM technique for patients diagnosed with achalasia, delving into critical aspects, such as the tailoring of the myotomy, the prevention of intraprocedural adverse events (AEs), the evaluation of long-term outcomes, and the feasibility of retreatment in cases of therapeutic failure.

Cricopharyngeal achalasia and upper oesophageal endoscopic myotomy (CP-POEM).

Cricopharyngeal achalasia (CPA), also known as cricopharyngeal bar, is a rare motor disorder affecting the upper oesophageal sphincter. This comprehensive literature review focuses on clinical aspects that can assist physicians in daily decision-making. The diagnosis of CPA is primarily based on symptoms of upper dysphagia and radiological identification of a posterior bar. However, the diagnostic process is not standardized and necessitates a multimodal approach, including radiological, endoscopic, and manometric studies performed by various specialists. Treatment options for CPA include botulinum toxin injection, endoscopic balloon dilatation, open or endoscopic surgery, and cricopharyngeal peroral endoscopic myotomy (CP-POEM). CP-POEM is the latest indication for POEM and has shown promising results with minimal adverse events, though high-quality evidence is still lacking.

Gastroesophageal reflux following peroral endoscopic myotomy for achalasia: Bumps in the road to success.

Achalasia can significantly impair the quality of life. The clinical presentation typically includes dysphagia to both solids and liquids, chest pain, and regurgitation. Diagnosis can be delayed in patients with atypical presentations, and they might receive a wrong diagnosis, such as gastroesophageal reflux disease (GERD), owing to overlapping symptoms of both disorders. Although the cause of achalasia is poorly understood, its impact on the motility of the esophagus and gastroesophageal junction is well established. Several treatment modalities have been utilized, with the most common being surgical Heller myotomy with concomitant fundoplication and pneumatic balloon dilatation. Recently, peroral endoscopic myotomy (POEM) has gained popularity as an effective treatment for achalasia, despite a relatively high incidence of GERD occurring after treatment compared to other modalities. The magnitude of post-POEM GERD depends on its definition and is influenced by patient and procedure-related factors. The long-term sequelae of post-POEM GERD are yet to be determined, but it appears to have a benign course and is usually manageable with clinically available modalities. Identifying risk factors for post-POEM GERD and modifying the POEM procedure in selected patients may improve the overall success of this technique.

Diagnostic Utility of High-resolution Esophageal Manometry and Its Correlation with Symptoms.

BACKGROUND: Primary esophageal motility disorders present with a spectrum of symptoms where manometry plays an important role. We designed this study to evaluate the utility of esophageal manometry among various symptoms. MATERIALS AND METHODS: This is a single-center observational study conducted over 5 years in a tertiary referral center. A total of 564 patients who underwent high-resolution esophageal manometry (HREM) using a 16-channel water perfusion system were included in the study. Their clinical profile and manometric findings, as per the Chicago classification version 4.0, were recorded, and the diagnostic utility of HREM with respect to symptoms was studied. RESULTS: Motility disorders were identified in 48.8% of patients, the most common being Achalasia cardia (32.4%). Dysphagia (55.5%) was the most common indication of manometry, followed by gastroesophageal reflux disease (GERD) (34.9%), chest pain (6.2%), and symptoms such as belching, globus, and hiccoughs (3.4%). Among those who were re-classified from Chicago classification v3.0 to v4.0, 21.2% had a newer diagnosis. Among the patients with dysphagia, HREM revealed the highest yield of detecting an abnormal esophageal motility test (70.6%); meanwhile, this yield was much lower in those with GERD (21.8%), chest pain (22.8%), and other symptoms (15.7%). The most common finding among those with dysphagia was Achalasia cardia (55.9%), while the study was normal among those with GERD (78.1%), chest pain (77.1%), and other symptoms (84.2%). The sensitivity and specificity of dysphagia for major motility disorders were 65% and 91%, respectively, with a positive predictive value of 90%. CONCLUSION: HREM has high accuracy and a good diagnostic yield among patients with dysphagia, with the most common finding being Achalasia cardia.

Résumé Contexte:Les troubles primaires de la motilité œsophagienne se manifestent par un spectre de symptômes dans lesquels la manométrie joue un rôle important. Nous conçu cette étude pour évaluer l'utilité de la manométrie œsophagienne parmi divers symptômes.Matériels et méthodes:Il s'agit d'un centre unique étude observationnelle menée sur 5 ans dans un centre de référence tertiaire. Au total, 564 patients ayant subi une chirurgie œsophagienne à haute resolution la manométrie (HREM) utilisant un système de perfusion d'eau à 16 canaux ont été incluses dans l'étude. Leur profil clinique et leurs résultats manométriques, selon la classification de Chicago version 4.0, ont été enregistrés et l'utilité diagnostique du HREM en ce qui concerne les symptômes a été étudiée.Résultats:Des troubles de la motilité ont été identifiés chez 48,8 % des patients, la plus fréquente étant l'Achalasia cardia (32,4 %). La dysphagie (55,5 %) était la l'indication la plus courante de la manométrie, suivie du reflux gastro-œsophagien (RGO) (34,9 %), des douleurs thoraciques (6,2 %) et des symptômes tels que comme les éructations, les globus et le hoquet (3,4 %). Parmi ceux qui ont été reclassés de la classification de Chicago v3.0 à v4.0, 21,2 % avaient un diagnostic. Parmi les patients atteints de dysphagie, l'HREM a révélé le rendement le plus élevé de détection d'un test de motilité œsophagienne anormale (70,6 %); dans le même temps, ce rendement était beaucoup plus faible chez les personnes souffrant de RGO (21,8 %), de douleurs thoraciques (22,8 %) et d'autres symptômes (15,7 %). Le plus courant le résultat parmi les personnes souffrant de dysphagie était l'achalasie cardiaque (55,9 %), tandis que l'étude était normale chez les personnes souffrant de RGO (78,1 %), douleur thoracique (77,1 %) et autres symptômes (84,2 %). La sensibilité et la spécificité de la dysphagie pour les troubles majeurs de la motilité étaient de 65 % et 91 %, respectivement, avec une valeur prédictive positive de 90 %.Conclusion:HREM présente une grande précision et un bon rendement diagnostique chez les patients atteints de dysphagie, la pathologie la plus fréquente étant l'achalasie cardiaque.

The effect of per-oral endoscopic myotomy by achalasia subtype as measured by impedance planimetry.

BACKGROUND: Achalasia is an esophageal motility disorder with three subtypes based on manometry that can treated with per-oral endoscopic myotomy (POEM). With the advent of impedance planimetry (EndoFLIP®), we hypothesized the three achalasia subtypes would have different pre-POEM EndoFLIP® diameter and distensibility index (DI) measurements but would be similar after POEM. METHODS: A single-institution, retrospective review of consecutive POEM cases by a single surgeon-endoscopist team from 04/07/2017 to 08/28/2023. Patients with a diagnosis of achalasia were stratified into type 1, 2, or 3 based on pre-POEM manometry. Patient characteristics, Eckardt scores, and pre-and-post-POEM diameter and DI were compared by subtype with descriptive, univariate, and multivariable linear regression statistics. RESULTS: Sixty-four patients met inclusion criteria, of whom 9(14.1%) had Type 1, 36(56.3%) had Type 2, and 19(29.7%) had Type 3. There were no differences between Types with respect to median pre-POEM Eckardt scores (9[IQR:7-9) vs. 8[IQR:6-9] vs. 7[IQR:5-8], p = 0.148), median post-POEM Eckardt scores (0[IQR:0-1] vs. 0[IQR:0-0] vs. 0[IQR0-0.5], p = 0.112). EndoFLIP® data revealed variation in median pre-POEM diameter and DI between Subtypes (6.9[IQR:6-8.5] vs. 5.5[IQR:5-6.8] vs. 5[IQR:5-6.1], p = 0.025 and 1.8[IQR:1.3-3.2] vs. 0.9[IQR:0.6-1.6] vs. 0.6[IQR:0.5-0.8], p = 0.003, respectively), but not in the change in diameter or DI post-POEM (5.1[IQR:4.3-5.9] vs. 5.1[IQR:4.1-7.1] vs. 5.9[IQR:5-6.4], p = 0.217 and 3.9[IQR:2.5-4.7] vs. 3.4[IQR:2.4-4.7] vs. 2.7[IQR:2.3-3.7], p = 0.461, respectively). However, after adjusting for potentially confounding factors, pre- or post-POEM diameter and DI did not demonstrate statistically significant differences among subtypes. CONCLUSIONS: Achalasia subtypes did not demonstrate different pre-POEM diameters or DI as measured by EndoFLIP® nor are there differences after POEM completion. While achalasia subtypes may have slightly different pathophysiology based on manometry findings, similar pre- and post-POEM impedance planimetry findings, along with similar Eckardt scores, support the use of POEM in the treatment of any achalasia subtype.

Gastroesophageal reflux after per-oral endoscopic myotomy: Management literature.

In this editorial, we respond to a review article by Nabi et al, in which the authors discussed gastroesophageal reflux (GER) following peroral endoscopic myotomy (POEM). POEM is presently the primary therapeutic option for achalasia, which is both safe and effective. A few adverse effects were documented after POEM, including GER. The diagnostic criteria were not clear enough because approximately 60% of patients have a long acid exposure time, while only 10% experience reflux symptoms. Multiple predictors of high disease incidence have been identified, including old age, female sex, obesity, and a baseline lower esophageal sphincter pressure of less than 45 mmHg. Some technical steps during the procedure, such as a lengthy or full-thickness myotomy, may further enhance the risk. Proton pump inhibitors are currently the first line of treatment. Emerging voices are increasingly advocating for the routine combining of POEM with an endoscopic fundoplication method, such as peroral endoscopic fundoplication or transoral incisionless fundoplication. However, more research is necessary to determine the safety and effectiveness of these procedures in the long term for patients who have undergone them.

Gastroesophageal reflux following per-oral endoscopic myotomy: Can we improve outcomes?

This editorial is an analysis the review article by Nabi et al recently published in this journal. Achalasia Cardia is a disease whose pathophysiology is still unclear. It is known that there is inflammation of unknown aetiology leading to loss of ganglion cells in the muscularis propria. The end result is lower oesophageal sphincter spasm, loss of receptive relaxation, decreased oesophageal peristalsis, all leading on to varying degrees of dysphagia. The treatment of this condition is palliative in nature, performed by myotomy of the lower oesophagus either surgically or endoscopically. Gastroesophageal reflux disease (GERD) has been associated with the myotomy performed, particularly with the Peroral Endoscopic Myotomy (POEM) procedure. Nabi et al have provided an excellent overview of the latest developments in predicting, preventing, evaluating, and managing GERD subsequent to POEM. Based on this theme, this review article explores the concept of using histology of the oesophageal muscle layer, to grade the disease and thereby help tailoring the length/type of myotomy performed during the POEM procedure. In the future, will a histology based algorithm available preoperatively, help modify the POEM procedure, thereby decreasing the incidence of GERD associated with POEM?

Two onset types of achalasia and the long-term course to diagnosis.

BACKGROUND: Recently, the incidence of achalasia has been increasing, but its cause remains unknown. This study aimed to examine the initial symptoms and the course of symptoms and to find new insights into the cause and course of the disease. METHODS: Altogether, 136 patients diagnosed with achalasia by high-resolution manometry (HRM) were enrolled. Questionnaires and chart reviews were conducted to investigate the initial symptoms, time from onset to diagnosis, and comorbidities, as well as the relationship between HRM results, time to diagnosis, and symptom severity. RESULTS: In total, 67 of 136 patients responded to the questionnaire. The median ages of onset and diagnosis were 42 and 58 years, respectively. The median time from onset to diagnosis was 78.6 months, with 25 cases (37.3%) taking > 10 years to be diagnosed. The symptom onset was gradual and sudden in 52 (77.6%) and 11 (16.4%) patients, respectively. Of the 11 patients with acute onset, three (27.3%) developed anhidrosis at the same time. There was no correlation between the time from onset to diagnosis and esophageal dilatation, resting LES pressure, or mean integrated relaxation pressure (IRP). No correlation was also found between the degree of symptoms and resting LES pressure or IRP. CONCLUSION: Esophageal achalasia can have acute or insidious onsets. This finding may help to elucidate the cause of achalasia.

Navigating reflux disease after achalasia treatments: Balancing risks and benefits.

The peroral endoscopic myotomy (POEM) procedure has revolutionized the management of achalasia in many centres around the world as it offers patients a minimally invasive endoscopic solution to their dysphagia caused by achalasia. Alongside its success in alleviating dysphagia, concerns regarding postoperative gastroesophageal reflux disease have emerged as a pertinent issue which are not fully resolved. In this study, Nabi et al have comprehensively reviewed the topic of the prediction, prevention and management of gastroesophageal reflux after POEM. POEM is a purely endoscopic procedure which is usually performed without any anti-reflux procedure. Certain patients may be better served by a laparoscopic Heller's myotomy and fundoplication and it is important that gastroenterologists and surgeons provide comprehensive risks and benefits of each achalasia treatment option so that patients can decide what treatment is best for them. This article by Nabi et al provides a comprehensive review of the current status of this issue to allow these discussions to occur.

Primary achalasia diagnosed during pregnancy: rare cause of nausea and vomiting.

Nausea and vomiting during pregnancy are very common; however, when persistent symptoms lead to severe malnutrition, other conditions should be considered. We present a patient with severe postprandial nausea and vomiting resulting in 120 lb weight loss. She was treated for presumed hyperemesis gravidarum but diagnosed with achalasia type 1 upon further work-up. The pregnancy was further complicated by fetal growth restriction, shortened cervix and preterm premature rupture of membranes, and resulted in delivery at 26 weeks of gestation. Postpartum, she underwent a peroral endoscopic myotomy procedure and has returned to normal body mass index.The differential for nausea/vomiting is broad, and major medical conditions can manifest for the first time during pregnancy. Severe malnutrition adversely affects maternal and fetal health. Further work-up should be pursued when symptoms cannot otherwise be explained.

Novel scale for evaluating the therapeutic efficacy of per-oral endoscopic myotomy in achalasia.

BACKGROUND: Symptom scales for achalasia after per-oral endoscopic myotomy (POEM) are lacking. This study aimed to propose a new scale based on the conventional Eckardt score (c-ES) and evaluate persistent symptoms that impair patients' quality of life (QOL) post-POEM. METHODS: Dysphagia, regurgitation, and chest pain frequencies were assessed using a 6-point scale modified-ES (m-ES) after POEM, with "occasional" symptoms on the c-ES further subdivided into three-period categories on m-ES. Symptom severity was further evaluated using a 5-point scale ranging from 1 to 5 points, with a score ≥ 3 points defined as persistent symptoms impairing QOL. We analyzed the correlation between the m-ES and severity score, diagnostic performance of the m-ES for persistent symptoms, and overlaps between each residual symptom. RESULTS: Overall, 536 patients (median follow-up period, 2.9 years) post-POEM were included in this multicenter study. Significant correlations were observed between the m-ES and severity scores for dysphagia (r = 0.67, p < 0.01), regurgitation (r = 0.73, p < 0.01), and chest pain (r = 0.85, p < 0.01). Twenty-six patients (4.9%) had persistent symptoms post-POEM, and 23 of them had m-ES-specific symptom frequency ≥ once a month, which was determined as the optimal frequency threshold for screening persistent symptoms. The total m-ES predicted persistent symptoms more accurately than the total c-ES (area under the curve: 0.95 vs. 0.79, p < 0.01). Furthermore, dysphagia and chest pain were the major residual symptoms post-POEM covering 91.4% of regurgitation. CONCLUSIONS: The new post-POEM scale successfully evaluated the QOL-based patient symptom severities. Our study implied the possibility of a simpler scale using residual dysphagia and chest pain.

Achalasia in pregnancy.

Achalasia is characterised by incomplete relaxation of the lower oesophageal sphincter and aberrant oesophageal peristaltic activity resulting in impaired oesophageal emptying. This rare condition in pregnancy is unique as both the disease and its treatment are associated with fetomaternal risks and complications. A woman in her early 30s, gravida 3 para 2 at 35 weeks' pregnancy with suspected oesophageal achalasia, presented with shortness of breath, cough and fever following frequent bouts of vomiting and fluid regurgitation. She was diagnosed with aspiration pneumonia complicated by severe metabolic acidosis, malnutrition syndrome and fetal growth restriction. Following stabilisation of the acute clinical problems, delivery was expedited via caesarean section. Postpartum endoscopy confirmed the diagnosis of achalasia as per initial suspicion. Definitive surgery was performed several months later after optimisation of the patient's nutritional status. This case illustrates the life-threatening complications of achalasia in pregnancy.

The evolution of the treatment of esophageal achalasia. Chronicle of a 35-year journey.

Over the last few decades, significant improvement has been made in both the evaluation and treatment of esophageal achalasia. The Chicago classification, today in version 4.0, is now the standard for diagnosis of achalasia, providing a classification into 3 subtypes with important therapeutic and prognostic implications. Therapy, which was at first mostly limited to pneumatic dilatation, today includes minimally invasive surgery and peroral endoscopic myotomy, allowing for a more tailored approach to patients and better treatment of recurrent symptoms. This review chronicles my personal experience with achalasia over the last 35 years, describing the progress made in the treatment of patients with achalasia.

Laparoscopic heller myotomy versus peroral endoscopic myotomy for the treatment of achalasia.

PURPOSE OF REVIEW: To compare different therapeutic modalities and determine their role in the treatment of esophageal achalasia. RECENT FINDINGS: The last 3 decades have seen a significant improvement in the diagnosis and treatment of esophageal achalasia. Conventional manometry has been replaced by high-resolution manometry, which has determined a more precise classification of achalasia in three subtypes, with important treatment implications. Therapy, while still palliative, has evolved tremendously. While pneumatic dilatation was for a long time the main choice of treatment, this approach slowly changed at the beginning of the nineties when minimally invasive surgery was adopted, initially thoracoscopically and then laparoscopically with the addition of partial fundoplication. And in 2010, the first report of a new endoscopic technique - peroral endoscopic myotomy (POEM) - was published, revamping the interest in the endoscopic treatment of achalasia. SUMMARY: This review focuses particularly on the comparison of POEM and laparoscopic Heller myotomy (LHM) with partial fundoplication as primary treatment modality for esophageal achalasia. Based on the available data, we believe that LHM with partial fundoplication should be the primary treatment modality in most patients. POEM should be selected when surgical expertise is not available, for type III achalasia, for the treatment of recurrent symptoms, and for patients who had prior abdominal operations that would make LHM challenging and unsafe.