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    Factors predictive of gastroesophageal reflux disease and esophageal motility disorders in patients with non-cardiac chest pain. Gomez Cifuentes Juan,Lopez Rocio,Thota Prashanthi N Scandinavian journal of gastroenterology BACKGROUND:Patients with non-cardiac chest pain (NCCP) are referred for esophageal motility testing and pH monitoring since gastroesophageal reflux disease (GERD) and esophageal motility disorders are frequently encountered in these patients. Our aim was to determine the prevalence and distribution of these disorders and to identify predictors of abnormal esophageal function testing. METHODS:We performed a retrospective study of NCCP patients who presented after a negative cardiac evaluation and underwent esophageal manometry, esophageal pH monitoring and upper endoscopy from January 2010 to January 2017. KEY RESULTS:In a total of 177 patients, esophageal motility disorders were diagnosed in 31% and GERD in 35% of the patients. The most common diagnoses were ineffective esophageal motility (IEM) in 14.1%, jackhammer esophagus in 6.8%, diffuse esophageal spasm in 5.1% and achalasia in 2.3% patients. Older age [for every 5-year increment, odds ratio (OR) 1.2 (95% confidence intervals (CI) 1.00-1.3) p = .047] and dysphagia [OR 3.8 (95% CI, 1.9-7.5) p < .001] were predictors of esophageal motility disorders. Older age [for every 5-year increment, OR 1.2 (95% CI, 1.01-1.3) p = .032] was predictive of GERD. Abnormal esophageal testing was associated with male gender [OR 2.2 (95% CI, 1.04-4.6) p = .039], older age [for every 5-year increment, OR 1.2 (95% CI, 1.03-1.3) p = .016] and Caucasian race [OR 3.1 (95% CI, 1.1-8.7) p < .029]. CONCLUSIONS:Approximately two thirds of patients presenting with NCCP have GERD or esophageal motility disorders. Esophageal function testing in NCCP should be considered in older patients, men, Caucasians and those presenting with dysphagia. 10.1080/00365521.2018.1452975
    Esophageal motility disorders: new perspectives from high-resolution manometry and histopathology. Sato Hiroki,Takahashi Kazuya,Mizuno Ken-Ichi,Hashimoto Satoru,Yokoyama Junji,Hasegawa Go,Terai Shuji Journal of gastroenterology High-resolution manometry (HRM) and peroral endoscopic myotomy (POEM) have contributed significantly to the field of esophageal motility disorders in recent years. The development of HRM has categorized various esophageal motility disorders with a focus on a diverse range of manometric anomalies. Additionally, the Chicago classification criteria is widely used for manometric diagnosis. Moreover, POEM was introduced as a minimally invasive radical therapy for achalasia and shows promise for other spastic esophageal motility disorders as well. POEM has also enabled a transluminal endoscopic approach for determining the histology of the esophageal muscle layer, which is expected to assist in elucidating the etiology of disorders associated with esophageal motility. The purpose of this review is to update the diagnosis, pathology, and treatment of esophageal motility disorders, with a focus on the recent advances in this field. 10.1007/s00535-017-1413-3
    Two types of autologous cells in stricture development prevention after complete circular endoscopic dissection in minipig. Juhásová J,Klíma J,Martínek J,Walterová B,Dolezel R,Vacková Z,Kollár M,Juhas S Rozhledy v chirurgii : mesicnik Ceskoslovenske chirurgicke spolecnosti INTRODUCTION:Complete circular endoscopic dissection (CED) is frequently accompanied with post-operative strictures formation in the esophagus. Various types of therapeutic approaches have recently been tested to prevent these strictures, e.g. cell therapy or stenting. METHODS:Miniature pigs of Gottingen/Minnesota origin (n=10) were used in the study. First, we made the complete CED in the mid esophagus; next, the defect was left untreated or covered with mesenchymal stem cells (MSCs) or a mixture of MSCs and primary oral keratinocytes (pOKs) suspension without/with fully covered self-expandable metallic stent (SEMS). Consequently, we performed a control endoscopy with a stent removal, and necropsy was performed 17-36 days after cells application. RESULTS:All CED procedures were completed successfully without serious complications. Although we were able to detect MSCs or pOKs in the post-CED defects up to the 36th day after transplantation, the combination of MSCs or MSCs/pOKs with or without SEMS application did not prevent post-CED strictures development. The mixture of MSCs and pOKs resulted in the formation of cellular aggregates, which were mainly observed in submucosa, and the post-CED defect was covered with collagen fibers containing a thin scarred epithelium, accompanied by various degrees of reconstruction and integrity. CONCLUSION:Suspension application of autologous MSCs alone or in combination with pOKs with or without SEMS was ineffective in the prevention of strictures formation after complete CED. Nevertheless, the presence of MSCs or pOKs in the post-CED defect was confirmed even 5 weeks after transplantation. 10.33699/PIS.2019.98.12.497-508
    Treatment of experimental esophagogastric myotomy with bone marrow mesenchymal stem cells in a rat model. Mazzanti B,Lorenzi B,Lorenzoni P,Borghini A,Boieri M,Lorenzi M,Santosuosso M,Bosi A,Saccardi R,Weber E,Pessina F Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society BACKGROUND:Over the last 15 years, many studies demonstrated the myogenic regenerative potential of bone marrow mesenchymal stem cells (BM-MSC), making them an attractive tool for the regeneration of damaged tissues. In this study, we have developed an animal model of esophagogastric myotomy (MY) aimed at determining the role of autologous MSC in the regeneration of the lower esophageal sphincter (LES) after surgery. METHODS:Syngeneic BM-MSC were locally injected at the site of MY. Histological and functional analysis were performed to evaluate muscle regeneration, contractive capacity, and the presence of green fluorescent protein-positive BM-MSC (BM-MSC-GFP(+) ) in the damaged area at different time points from implantation. KEY RESULTS:Treatment with syngeneic BM-MSC improved muscle regeneration and increased contractile function of damaged LES. Transplanted BM-MSC-GFP(+) remained on site up to 30 days post injection. Immunohistochemical analysis demonstrated that MSC maintain their phenotype and no differentiation toward smooth or striated muscle was shown at any time point. CONCLUSIONS & INFERENCES:Our data support the use of autologous BM-MSC to both improve sphincter regeneration of LES and to control the gastro-esophageal reflux after MY. 10.1111/nmo.12182
    Tissue engineered esophagus by mesenchymal stem cell seeding for esophageal repair in a canine model. Tan Bo,Wei Ren-Qian,Tan Mei-Yun,Luo Jing-Cong,Deng Li,Chen Xiao-He,Hou Jiang-Long,Li Xiu-Qun,Yang Zhi-Ming,Xie Hui-Qi The Journal of surgical research PURPOSE:Acellular porcine small intestinal submucosa (SIS) has been successfully used for esophagoplasty in dogs. However, this has not led to complete epithelialization and muscular regeneration. We undertook the present study to assess the effect of tissue-engineered esophagus generated by seeding bone marrow mesenchymal stem cells (BMSCs) onto an SIS scaffold (BMSCs-SIS) in a canine model. METHODS:We cultured, passaged, and measured autologous BMSCs and myoblasts with cell proliferation and immunohistochemical assays. We labeled the third passage of BMSCs with PKH-26, a fluorescent dye, before seeded it onto the SIS. We resected canine cervical esophagus to generate a defect 5 cm in length and 50% in circumference, which we repaired with BMSCs-SIS or SIS alone. RESULTS:Four weeks later, barium esophagram demonstrated that esophageal lumen surface of the patch graft was smoother in the BMSCs-SIS group compared with the SIS group. Histological examination suggested a strong similarity between BMSCs and esophageal myoblasts in terms of morphology and function. Although both BMSCs-SIS and SIS repaired the esophageal defects, we noted complete re-epithelialization with almost no inflammation only in the former group. By 12 wk after the surgery, we observed long bundles of skeletal muscles only in the BMSCs-SIS group, where the microvessel density was also much greater. CONCLUSIONS:Bone marrow mesenchymal stem cells on an SIS scaffold can promote re-epithelialization, revascularization, and muscular regeneration. This approach may provide an attractive option for esophageal regeneration. 10.1016/j.jss.2012.07.054
    Oral administration of conditioned medium obtained from mesenchymal stem cell culture prevents subsequent stricture formation after esophageal submucosal dissection in pigs. Mizushima Takeshi,Ohnishi Shunsuke,Hosono Hidetaka,Yamahara Kenichi,Tsuda Momoko,Shimizu Yuichi,Kato Mototsugu,Asaka Masahiro,Sakamoto Naoya Gastrointestinal endoscopy BACKGROUND AND AIMS:Endoscopic submucosal dissection (ESD) for esophageal cancer often causes postoperative stricture when more than three fourths of the circumference of the esophagus is dissected. Mesenchymal stem cells are a valuable cell source in regenerative medicine, and conditioned medium (CM) obtained from mesenchymal stem cells reportedly inhibits inflammation. In this study we evaluated whether CM could prevent esophageal stricture after ESD. METHODS:We resected a semi-circumference of pig esophagus by ESD. We prepared CM gel by mixing with 5% carboxymethyl cellulose and endoscopically applied it onto the wound bed immediately after ESD and on days 8 and 15 (weekly CM group) or administered it orally from days 1 to 4 (daily CM group). We also injected triamcinolone acetonide into the remaining submucosa immediately after ESD (steroid group). We killed the pigs on day 8 or day 22 to measure the stricture rate and to perform histologic analysis. RESULTS:Stricture rate in weekly and daily CM groups and steroid groups were significantly lower than in the control group on day 22. Moreover, CM significantly attenuated the number of activated myofibroblasts and fiber thickness on day 22. CM also significantly decreased the infiltration of neutrophils and macrophages compared with the control group on day 8. CONCLUSIONS:CM gel prevents esophageal stricture formation by suppressing myofibroblast activation and fibrosis after the infiltration of neutrophils and macrophages. Oral administration of CM gel is a promising treatment for the prevention of post-ESD stricture. 10.1016/j.gie.2017.01.024
    Anatomic-manometric correlation of the upper esophageal sphincter: a concurrent US and manometry study. Hernandez Lyndon V,Dua Kulwinder S,Surapaneni Sri Naveen,Rittman Tanya,Shaker Reza Gastrointestinal endoscopy BACKGROUND:The pharyngoesophageal segment commonly referred to as the upper esophageal sphincter (UES) generates a high-pressure zone (HPZ) between the pharynx and the esophagus. However, the exact anatomical components of the UES-HPZ remain incompletely determined. OBJECTIVE:To systematically define the US signature of various components of the pharyngoesophageal junction and to determine how these structures contribute to the development of the UES-HPZ. DESIGN:Prospective, experimental study. SETTING:Tertiary Academic Medical Center. PATIENTS:This study involved 18 healthy volunteers. INTERVENTION:We studied 5 participants by using a high-frequency US miniprobe (US-MP) and concurrent fluoroscopy and another 13 participants by using the US-MP and concurrent manometry. MAIN OUTCOME MEASUREMENTS:Relative contribution of various muscles in the UES-HPZ. RESULTS:Manometrically, the UES-HPZ had a median length of 4.0 cm (range 3.0-4.5 cm). A C-shaped muscle, believed to represent the cricopharyngeus muscle, was observed for a median length of 3.5 cm (range 2.0-4.0 cm). The oval configuration representing the esophageal contribution to the UES was seen in 10 of 13 participants (77%) at the distal HPZ (esophagus to UES transition zone). The flat configuration of the inferior constrictor muscle was noted in 7 of 13 participants (54%) at the proximal HPZ (UES to pharynx transition zone). There were 4 to 5 wall layers versus 3 layers in the distal and proximal HPZ, respectively. The mean (+/- SD) muscle thickness was relatively constant along the length of the UES-HPZ. LIMITATIONS:Air artifacts in the UES-HPZ. CONCLUSION:The configuration and layers of the UES-HPZ vary along its length. The upper esophagus is a significant contributor to the distal UES-HPZ. 10.1016/j.gie.2010.04.029
    A case of diffuse esophageal spasm successfully treated by steroid therapy. Funaki Yasushi,Iida Akihito,Shimozato Akihiro,Yamaguchi Junji,Tanabe Atsushi,Tamura Yasuhiro,Izawa Shinya,Ogasawara Naotaka,Sasaki Makoto,Kasugai Kunio Nihon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology A 53-year-old man was admitted to our hospital with anterior chest pain and difficulty swallowing. Computed tomography revealed significant esophageal wall thickening. Esophageal intraluminal manometry revealed uncoordinated contraction and strong peristaltic pressure associated with the chest pain. The patient was subsequently diagnosed with diffuse esophageal spasm (DES). His serum immunoglobulin E level was high, and peripheral blood eosinophilia was observed. No eosinophilic infiltration was detected in the esophageal mucosa on endoscopic biopsy. It was presumed that this case of DES was induced by allergic disease. Treatment with 30 mg of oral prednisolone led to a prompt resolution of symptoms;the thickness of the esophageal wall decreased, and the simultaneous contractions disappeared. However, given the presence of a strong peristaltic wave, nutcracker esophagus (NE) was also suspected. This was a rare case of atypical DES induced by allergic disease and associated with NE.
    Calculation of esophageal variceal wall tension by ultrasonic microprobe and noninvasive pressure measurements. Zhu Saihong,Liu Xunyang,Huang Feizhou,Nei Wanping,Liu Bo,Li Reizheng,Cai Lifeng,Wang Wei,Yang Minshi,Ren Shuping Romanian journal of gastroenterology OBJECTIVE:To calculate esophageal variceal wall tension by sonographic and noninvasive pressure measurements and to study the role of esophageal variceal wall tension in predicting the likelihood of esophageal variceal rupture. METHODS:In 28 patients with esophageal varices, a 20 MHz ultrasonographic transducer was used to image esophageal varices; the radius and wall thickness of the varices were calculated. Esophageal variceal pressure measurements were obtained noninvasively. The correlation between the esophageal wall tension and esophageal variceal pressure gradient were studied. RESULTS:There was a linear correlation between the esophageal wall tension and the variceal pressure gradient after curve fitting (r=0.87, p < 0.05). CONCLUSION:Esophageal variceal wall tension is an important parameter in predicting variceal rupture.
    Relationship between esophageal muscle thickness and intraluminal pressure: an ultrasonographic study. Pehlivanov N,Liu J,Kassab G S,Puckett J L,Mittal R K American journal of physiology. Gastrointestinal and liver physiology A number of studies show a close temporal relationship between the rate of change in muscle thickness as detected by high-frequency intraluminal ultrasonography (HFIUS) and intraluminal pressure measured by manometry. There is a marked variability in esophageal contraction amplitude from one swallow to another at a given level in the esophagus and along the length of the esophagus. Furthermore, peristaltic pressures are higher in the distal compared with the proximal esophagus. The goal of this study was to evaluate the relationship between the baseline and peak muscle thickness and the contraction amplitude during swallow-induced contractions along the length of the esophagus. Fifteen normal subjects were studied using simultaneous esophageal pressures and HFIUS or HFIUS alone. Recordings were made during baseline and standardized swallows in the lower esophageal sphincter (LES) and at 2, 4, 6, 8, and 10 cm above the LES. HFIUS images were digitized, and esophageal muscle thickness and peak contraction amplitudes were measured. In the resting state, muscle thickness is higher in the LES compared with the rest of the esophagus. Baseline muscle thickness is also significantly higher at 2 cm vs. 10 cm above the LES. In a given subject and among different subjects, there is a good relationship between peak muscle thickness and peak peristaltic pressures (r = 0.55) at all sites along the length of the esophagus. The positive correlation between pressure and muscle thickness implies that the mean circumferential wall stress is fairly uniform from one swallow to another, irrespective of the contraction amplitude. 10.1152/ajpgi.2001.280.6.G1093
    Vascular pressure bands on high-resolution esophageal manometry with impedance studies. Lis Steffen,Vachhani Herit,Tanner Samuel,Leopold Andrew,Zitomer Samantha,Bhuta Rajiv,Schey Ron,Malik Zubair,P Parkman Henry Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus Horizontal pressure bands on high-resolution esophageal manometry with impedance (HREMI) tracings are often seen and thought to be due to cardiovascular structures compressing the esophagus. The aim of this study was to determine the prevalence and location of vascular pressure bands on HREMI studies and correlate these pressure bands to bolus clearance. HREMI studies in supine and upright positions from patients and normal volunteers were reviewed. Pressure bands were defined as bands of horizontal pressure greater than the 20 mmHg isobaric contour. Each swallow was reviewed with impedance to determine if bolus transit was impaired by the band. 38.6% of 251 patients and 36.4% of 11 normal controls had a pressure band present. There were a greater number of bands in supine versus upright position (patients: 130 vs. 25, P < 0.001 and controls: 6 vs. 1). Patients with pressure bands had similar demographics (age, gender, BMI) compared to those without. Average distal contractile integral of bands was greater in supine compared to upright (133 ± 201 vs. 60 ± 148 mmHg cm s, P < 0.05). Bands were commonly located clustered at 46 and 72% of esophageal length. Bolus transit was impaired by bands in 20.4% of supine and 14.0% of upright swallows. Vascular pressure bands can have a prominent appearance on HREMI studies, present in, being more prevalent and having greater pressure in the supine than the upright position. These vascular bands, when present, may impair esophageal transit. 10.1093/dote/doz093