RESUMEN
BACKGROUND AND AIMS: Peroral endoscopic myotomy (POEM) is conducted for patients with esophageal motility disorders based on high-resolution manometry (HRM) findings. However, the impact of POEM on HRM findings and the associations between post-POEM HRM and outcomes have not been clarified. METHODS: In a multicenter, observational, cohort study, patients with achalasia treated by POEM received follow-up HRM. Associations between patient characteristics, POEM procedures, and post-POEM HRM findings, including integrated relaxation pressure (IRP) and distal contractile integral (DCI), were investigated. Furthermore, POEM procedure outcomes were compared with post-POEM HRM findings. RESULTS: Of 2171 patients, 151 (7.0%) showed residual high post-POEM IRP (≥26 mm Hg; Starlet [Starmedical Ltd, Tokyo, Japan]). In a multivariate analysis, high pre-POEM IRPs (odds ratio [OR], 24.3) and gastric myotomy >2 cm (OR, .22) were found to be positive and negative predictive factors of high post-POEM IRPs, respectively. Peristalsis recovery (DCI ≥500 mm Hg/cm/s, at least 1 swallow; Starlet) was visible in 121 of 618 patients (19.6%) who had type II to III achalasia. High pre-POEM IRP (OR, 2.65) and DCI ≥500 (OR, 2.98) predicted peristalsis recovery, whereas esophageal dilation (OR, .42) predicted a risk of no recovery. Extended myotomy did not reveal a significant impact on peristalsis recovery. High or low post-POEM IRP and DCI did not increase the incidence of clinical failure, reflux esophagitis, or symptomatic GERD. CONCLUSIONS: Extended gastric myotomy decreased IRP values, whereas peristalsis recovery depended on the characteristics of achalasia. A residual high post-POEM IRP does not necessarily mean clinical failure. Routine HRM follow-up is not recommended after POEM.
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Acalasia del Esófago , Miotomía , Cirugía Endoscópica por Orificios Naturales , Humanos , Acalasia del Esófago/cirugía , Acalasia del Esófago/etiología , Esfínter Esofágico Inferior/cirugía , Estudios de Cohortes , Resultado del Tratamiento , Esofagoscopía/métodos , Cirugía Endoscópica por Orificios Naturales/efectos adversos , Manometría/métodos , Miotomía/métodosRESUMEN
BACKGROUND: Peroral endoscopic myotomy (POEM) is effective for the management of achalasia and its variants; however, it can be ineffective in some patients. We aimed to develop and validate a risk scoring system to predict the clinical failure of POEM preoperatively. METHODS: Consecutive patients who underwent POEM in 14 high volume centers between 2010 and 2020 were enrolled in this study. Clinical failure was defined as an Eckardt score ofâ≥â4 or retreatment. A risk scoring system to predict the short-term clinical failure of POEM was developed using multivariable logistic regression and internally validated using bootstrapping and decision curve analysis. RESULTS: Of the 2740 study patients, 112 (4.1â%) experienced clinical failure 6 months after POEM. Risk scores were assigned for three preoperative factors as follows: preoperative Eckardt score (1 point), manometric diagnosis (-4 points for type II achalasia), and a history of prior treatments (1 point for pneumatic dilation or 12 points for surgical/endoscopic myotomy). The discriminative capacity (concordance statistics 0.68, 95â%CI 0.62-0.72) and calibration (slope 1.15, 95â%CI 0.87-1.40) were shown. Decision curve analysis demonstrated its clinical usefulness. Patients were categorized into low (0-8 points; estimated risk of clinical failure <â5â%) and high risk (9-22 points; ≥â5â%) groups. The proportions of clinical failure for the categories were stratified according to the mid-term outcomes (log-rank test, Pâ<â0.001). CONCLUSIONS: This risk scoring system can predict the clinical failure of POEM preoperatively and provide useful information when making treatment decisions.
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Procedimientos Quirúrgicos del Sistema Digestivo , Acalasia del Esófago , Miotomía , Cirugía Endoscópica por Orificios Naturales , Humanos , Acalasia del Esófago/diagnóstico , Acalasia del Esófago/cirugía , Estudios de Casos y Controles , Cirugía Endoscópica por Orificios Naturales/efectos adversos , Miotomía/efectos adversos , Resultado del Tratamiento , Esfínter Esofágico Inferior/cirugía , Estudios RetrospectivosRESUMEN
BACKGROUND AND AIM: Absent contractility (AC) and ineffective esophageal motility (IEM) are esophageal hypomotility disorders diagnosed using high-resolution manometry (HRM). Patient characteristics and disease course of these conditions and differential diagnosis between AC and achalasia are yet to be elucidated. METHODS: A multicenter study involving 10 high-volume hospitals was conducted. Starlet HRM findings were compared between AC and achalasia. Patient characteristics including underlying disorders and disease courses were analyzed in AC and IEM. RESULTS: Fifty-three patients with AC and 92 with IEM were diagnosed, while achalasia was diagnosed in 1784 patients using the Chicago classification v3.0 (CCv3.0). The cut-off integrated relaxation pressure (IRP) value at 15.7 mmHg showed maximum sensitivity (0.80) and specificity (0.87) for differential diagnosis of AC from type I achalasia. While most ACs were based on systemic disorders such as scleroderma (34%) and neuromuscular diseases (8%), 23% were sporadic cases. The symptom severity of AC was not higher than that of IEM. Regarding the diagnosis of IEM, the more stringent CCv4.0 excluded 14.1% of IEM patients than the CCv3.0, although patient characteristics did not change. In patients with the hypomotile esophagus, concomitance of reflux esophagitis was associated with low distal contractile integral and IRP values. AC and IEM transferred between each other, paralleling with the underlying disease course, although no transition to achalasia was observed. CONCLUSION: A successful determination of the optimal cut-off IRP value was achieved using the starlet HRM system to differentiate AC and achalasia. Follow-up HRM is also useful for differentiating AC from achalasia. Symptom severity may depend on underlying diseases instead of hypomotility severity.
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Acalasia del Esófago , Trastornos de la Motilidad Esofágica , Humanos , Acalasia del Esófago/diagnóstico , Trastornos de la Motilidad Esofágica/diagnóstico , Japón , ManometríaRESUMEN
OBJECTIVES: High-resolution manometry (HRM) and esophagography are used for achalasia diagnosis; however, achalasia phenotypes combining esophageal motility and morphology are unknown. Moreover, predicting treatment outcomes of peroral endoscopic myotomy (POEM) in treatment-naïve patients remains an unmet need. METHODS: In this multicenter cohort study, we included 1824 treatment-naïve patients diagnosed with achalasia. In total, 1778 patients underwent POEM. Clustering by machine learning was conducted to identify achalasia phenotypes using patients' demographic data, including age, sex, disease duration, body mass index, and HRM/esophagography findings. Machine learning models were developed to predict persistent symptoms (Eckardt score ≥3) and reflux esophagitis (RE) (Los Angeles grades A-D) after POEM. RESULTS: Machine learning identified three achalasia phenotypes: phenotype 1, type I achalasia with a dilated esophagus (n = 676; 37.0%); phenotype 2, type II achalasia with a dilated esophagus (n = 203; 11.1%); and phenotype 3, late-onset type I-III achalasia with a nondilated esophagus (n = 619, 33.9%). Types I and II achalasia in phenotypes 1 and 2 exhibited different clinical characteristics from those in phenotype 3, implying different pathophysiologies within the same HRM diagnosis. A predictive model for persistent symptoms exhibited an area under the curve of 0.70. Pre-POEM Eckardt score ≥6 was the greatest contributing factor for persistent symptoms. The area under the curve for post-POEM RE was 0.61. CONCLUSION: Achalasia phenotypes combining esophageal motility and morphology indicated multiple disease pathophysiologies. Machine learning helped develop an optimal risk stratification model for persistent symptoms with novel insights into treatment resistance factors.
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Shape-reconfigurable materials are crucial in many engineering applications. However, because of their isotropic deformability, they often require complex molding equipment for shaping. A polymeric origami structure that follows predetermined deformed and non-deformed patterns at specific temperatures without molding is demonstrated. It is constructed with a heterogeneous (dynamic and static) network topology via light-induced programming. The corresponding spatio-selective thermal plasticity creates varied deformability within a single polymer. The kinematics of site-specific deformation allows guided origami deployment in response to external forces. Moreover, the self-locking origami can fix its geometry in specific states without pressurization. These features enable the development of shape-reconfigurable structures that undergo on-demand geometry changes without requiring bulky or heavy equipment. The concept enriches polymer origamis, and could be applied with other polymers having similar chemistries. Overall, it is a versatile material for artificial muscles, origami robotics, and non-volatile mechanical memory devices.
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Polímeros , Robótica , Polímeros/química , TemperaturaRESUMEN
BACKGROUND AND AIMS: The etiology of chest pain in achalasia-related esophageal motility disorders and the frequency and risk factors of persistent chest pain after peroral endoscopic myotomy (POEM) remain unclear. METHODS: A multicenter cohort study including 14 hospitals was conducted to elucidate the characteristics of patients with chest pain and the efficacy of POEM. RESULTS: Consecutive cases of achalasia-related esophageal motility disorders included 2294 (64.2%) and 1280 (35.8%) patients with and without chest pain, respectively. Among the 2107 patients with chest pain who underwent POEM, we observed complete remission in 1464 patients (69.5%) and nonremission in 643 patients (30.5%), including a partial response in 619 patients (29.4%) and resistance in 24 patients (1.1%). Multivariate analysis revealed that advanced age (odds ratio [OR], .28), male sex (OR, .70), prior treatment (OR, 1.39), and sigmoid type (OR, .65) were related to the prevalence of chest pain. Long disease duration (OR, .69) and esophageal dilation (OR, .79) were related to decreased severity. POEM improved patients' quality of life that was hindered by chest pain. Early onset (OR, 1.45), advanced age (OR, .58), male sex (OR, .79), prior treatment (OR, 1.37), and posterior myotomy (OR, 1.42) were associated with nonremission after POEM; high-resolution manometry (HRM) findings and myotomy length showed no statistical significance on pain etiology and persistence after POEM. CONCLUSIONS: The prevalence and severity of chest pain were dependent on age, sex, disease duration, prior treatment, and esophageal morphology rather than HRM findings. The efficacy of POEM is satisfactory; however, residual pain was often observed. Excessively long myotomy can be avoided, and anterior myotomy may be recommended.
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Acalasia del Esófago , Trastornos de la Motilidad Esofágica , Miotomía , Cirugía Endoscópica por Orificios Naturales , Dolor en el Pecho/epidemiología , Dolor en el Pecho/etiología , Estudios de Cohortes , Acalasia del Esófago/etiología , Acalasia del Esófago/cirugía , Trastornos de la Motilidad Esofágica/epidemiología , Trastornos de la Motilidad Esofágica/etiología , Esfínter Esofágico Inferior/cirugía , Humanos , Japón/epidemiología , Masculino , Manometría/métodos , Miotomía/efectos adversos , Miotomía/métodos , Cirugía Endoscópica por Orificios Naturales/efectos adversos , Cirugía Endoscópica por Orificios Naturales/métodos , Calidad de Vida , Resultado del TratamientoRESUMEN
BACKGROUND : Gastroesophageal reflux disease (GERD) and reflux esophagitis remain problems after peroral endoscopic myotomy (POEM). This study aimed to elucidate the risk factors and long-term course of reflux esophagitis and symptomatic GERD after POEM. METHODS : This multicenter cohort study involved 14 high volume centers. Overall, 2905 patients with achalasia-related esophageal motility disorders treated with POEM were analyzed for reflux esophagitis, severe reflux esophagitis (Los Angeles classification C or D), and symptomatic GERD. RESULTS : Reflux esophagitis was diagnosed in 1886 patients (64.9â%). Age ≥â65 years (risk ratio [RR] 0.85), male sex (RR 1.11), posterior myotomy (RR 1.12), esophageal myotomy >â10âcm (RR 1.12), and gastric myotomy >â2âcm (RR 1.17) were independently associated with reflux esophagitis. Severe reflux esophagitis was diagnosed in 219 patients (7.5â%). Age ≥â65 years (RR 1.72), previous treatments (RR 2.21), Eckardt score ≥â7 (RR 0.68), sigmoid-type achalasia (RR 1.40), and esophageal myotomy >â10âcm (RR 1.59) were factors associated with severe reflux esophagitis. Proton pump inhibitors (PPIs) were more effective for reflux esophagitis at 5-year follow-up (Pâ=â0.03) than after 1 year (Pâ=â0.08). Symptomatic GERD was present in 458 patients (15.9â%). Symptom duration ≥â10 years (RR 1.28), achalasia diagnosis (RR 0.68), integrated relaxation pressure ≥â26 (RR 0.60), and posterior myotomy (RR 0.80) were associated with symptomatic GERD. The incidence of symptomatic GERD was lower at 5-year follow-up compared with that after 1 year (Pâ=â0.04), particularly in PPI users (Pâ<â0.001). CONCLUSIONS : The incidence of severe reflux esophagitis was low after POEM, but excessive myotomy for older patients with previous treatments should be avoided. Early phase symptomatic GERD is non-acid reflux dependent and the natural course is favorable, basically supporting conservative treatment.
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Acalasia del Esófago , Esofagitis Péptica , Reflujo Gastroesofágico , Miotomía , Cirugía Endoscópica por Orificios Naturales , Anciano , Estudios de Cohortes , Acalasia del Esófago/complicaciones , Acalasia del Esófago/epidemiología , Acalasia del Esófago/cirugía , Esfínter Esofágico Inferior/cirugía , Esofagitis Péptica/epidemiología , Esofagitis Péptica/etiología , Reflujo Gastroesofágico/epidemiología , Reflujo Gastroesofágico/etiología , Humanos , Japón/epidemiología , Masculino , Miotomía/efectos adversos , Miotomía/métodos , Cirugía Endoscópica por Orificios Naturales/efectos adversos , Cirugía Endoscópica por Orificios Naturales/métodos , Inhibidores de la Bomba de Protones , Factores de Riesgo , Resultado del TratamientoRESUMEN
INTRODUCTION: In patients with type 2 diabetes mellitus (T2DM), bone fragility increases fracture risk. Teriparatide (TPTD) improves bone strength, and exercise therapy suppresses blood glucose levels in T2DM. In this study, the combined effects of TPTD and exercise therapy on trabecular and cortical bone were examined in advanced T2DM model rats. MATERIALS AND METHODS: Thirty-week-old Otsuka Long-Evans Tokushima Fatty rats were divided into four groups (n = 9-10 in each group at two time points): Cont group (vehicle-treated control), TPTD group (TPTD 30 µg/kg injected subcutaneously, 3 times/week), Exe group (treadmill exercise, 10 m/min, 60 min/day, 5 times/week), and Comb group (TPTD-treated and treadmill exercise combined). Five and 10 weeks after treatment, bone mineral density (BMD), bone strength, and bone micro-architecture were measured. RESULTS: TPTD and combined treatment significantly increased BMDs of the lumbar spine and femur compared to the Cont group (p < 0.05 to p < 0.01). In the three-point bending test of the femur, only combined treatment increased the maximum load at 5 weeks compared with the Cont and Exe groups (p < 0.01). In the compression test of the distal femoral metaphysis, both TPTD and combined treatment increased the trabecular bone strength compared with the Cont and Exe groups (p < 0.05 to p < 0.01). Although TPTD and combined treatment improved the micro-architecture of trabecular bone (p < 0.05 to p < 0.01), only combined treatment improved the micro-structures of cortical bone from 5 weeks of treatment (p < 0.05 to p < 0.01). CONCLUSION: The combination of TPTD and treadmill exercise increased BMD and trabecular and cortical bone strength of the femur with improved micro-architecture in T2DM model rats.
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Conservadores de la Densidad Ósea , Enfermedades Óseas Metabólicas , Diabetes Mellitus Tipo 2 , Condicionamiento Físico Animal , Teriparatido , Animales , Densidad Ósea , Conservadores de la Densidad Ósea/farmacología , Enfermedades Óseas Metabólicas/terapia , Diabetes Mellitus Tipo 2/terapia , Ratas , Teriparatido/farmacologíaRESUMEN
BACKGROUND AND AIM: The perioperative management and clinical course of per-oral endoscopic myotomy for patients receiving antithrombotic therapy remains unknown. This study aimed to clarify the status of antithrombotic therapy in per-oral endoscopic myotomy and to determine its safety and efficacy. METHODS: Patients treated with per-oral endoscopic myotomy from 2010 to 2019 in seven high-volume centers in Japan were retrospectively investigated. The patients' characteristics and antithrombotic agent management were analyzed; clinical outcomes were compared with those without antithrombotic agents. RESULTS: Of 2752 patients who underwent per-oral endoscopic myotomy, 120 patients on antithrombotic therapy (mean age 71.0 years, American Society of Anesthesiologists class II-IV [67.5%]) were identified. Antiplatelet, anticoagulant, and a combination of antithrombotic agents were used in 82, 30, and 8 patients, respectively. The perioperative management adhered to the therapeutic endoscopy guidelines published by the Japanese Society of Gastroenterological Endoscopy in most patients (88.3%). A poorer clinical baseline status (American Society of Anesthesiologists class II-IV; 67.0% vs 24.3%) and the sigmoid type (40.7% vs 22.3%) were more frequently observed in patients with achalasia on antithrombotic therapy. However, the clinical success (Eckardt score ≤ 3; 97.6% vs 94.6) and adverse event rates, such as bleeding and thromboembolic events (5.5% vs 4.7%), did not show inferiority. CONCLUSIONS: Per-oral endoscopic myotomy on antithrombotic therapy is safe and effective. However, caution is required as patients on antithrombotic therapy tend to have poorer baseline health and achalasia statuses. Our experience should help establish perioperative management with antithrombotic therapy.
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Fibrinolíticos , Miotomía , Cirugía Endoscópica por Orificios Naturales , Anciano , Acalasia del Esófago/tratamiento farmacológico , Acalasia del Esófago/cirugía , Fibrinolíticos/uso terapéutico , Humanos , Japón , Miotomía/efectos adversos , Cirugía Endoscópica por Orificios Naturales/efectos adversos , Atención Perioperativa , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
AIM: To elucidate the impact of the coronavirus disease 2019 (COVID-19) on the practice of high-resolution manometry (HRM) and peroral endoscopic myotomy (POEM) in Japan. METHODS: We utilized a large-scale database involving 14 high-volume centers in Japan to investigate changes in the numbers of HRM and POEM procedures performed and outcomes of POEM between 2019 and 2020. A questionnaire survey was also conducted to analyze pandemic-associated changes in the HRM and POEM protocols. RESULTS: Compared to that in 2019, the number of HRM and POEM procedures decreased by 17.2% (1587-1314) and 20.9% (630-498), respectively. These declines were prominent during the state of emergency from April to May 2020, particularly in pandemic areas. HRM and POEM in nonpandemic areas were relatively unaffected. From 2019 to 2020, there was a 0.4% (254-248) decrease in POEM cases within the prefecture, but the number outside the prefecture decreased by 33.6% (372-247). During the pandemic, the safety and efficacy of POEM were maintained. The implementation of personal protective equipment (PPE) measures varied among facilities, and PPE for POEM was relatively insufficient compared to that for HRM. CONCLUSION: The COVID-19 pandemic influenced HRM and POEM practices in Japan. It is necessary to establish a sufficient system for HRM and POEM in each hospital as well as countrywide to overcome the effects of the pandemic.
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COVID-19 , Acalasia del Esófago , Trastornos de la Motilidad Esofágica , Miotomía , Cirugía Endoscópica por Orificios Naturales , COVID-19/epidemiología , Acalasia del Esófago/cirugía , Trastornos de la Motilidad Esofágica/cirugía , Esfínter Esofágico Inferior , Esofagoscopía/métodos , Humanos , Japón/epidemiología , Manometría/métodos , Miotomía/métodos , Cirugía Endoscópica por Orificios Naturales/métodos , Pandemias/prevención & control , Resultado del TratamientoRESUMEN
OBJECTIVES: Indications for peroral endoscopic myotomy (POEM) and endoscopic submucosal dissection (ESD) in patients with achalasia concomitant with esophageal carcinoma (EC) are unclear. This study aimed to clarify the role of POEM in cases of achalasia concomitant with EC and to elucidate the indications for ESD and efficient surveillance for EC. METHODS: We conducted a multicenter cohort study at 14 hospitals in Japan, including 3707 cases of achalasia-related esophageal motility disorders (EMDs). Factors contributing to EC risk, the characteristics of EC, and clinical outcomes of POEM/ESD were analyzed. RESULTS: In patients undergoing POEM, screening and surveillance endoscopy throughout a 1-year period resulted in diagnosis of 72.1% new EC cases. Of 62 patients with 123 ECs, 40.3% had multiple or metachronous lesions within 37.5 months. EC was predominantly observed in the middle thoracic esophagus (58.5%) and posteriorly (73.2%). POEM had comparable safety and efficacy in cases of concomitant EC even after ESD. Endoscopic en bloc resection was performed in 95.8% and 89.3% of ECs diagnosed before and after POEM, respectively (P = 0.351); however, ESD on the POEM-line was impaired by fibrosis. Multivariate analysis revealed risk factors for EC, including regular alcohol consumption, a history of smoking, advanced age, and extended disease duration. Alcohol intake and smoking had a synergistic effect on EC development. CONCLUSIONS: Screening and surveillance of POEM help in detecting EC. ESD is feasible in achalasia, although on the POEM-line is challenging. Surveillance endoscopy for EC is recommended for cases with specific risks and a history of ECs.
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Carcinoma , Resección Endoscópica de la Mucosa , Acalasia del Esófago , Miotomía , Cirugía Endoscópica por Orificios Naturales , Estudios de Cohortes , Endoscopía Gastrointestinal/métodos , Acalasia del Esófago/diagnóstico , Acalasia del Esófago/cirugía , Esfínter Esofágico Inferior/cirugía , Humanos , Japón/epidemiología , Miotomía/métodos , Cirugía Endoscópica por Orificios Naturales/métodos , Resultado del TratamientoRESUMEN
OBJECTIVES: Patients with esophageal motility disorders (EMDs) including achalasia after gastric surgery have not been thoroughly characterized. Furthermore, the efficacy of peroral endoscopic myotomy (POEM) in this population should be clarified. METHODS: In this retrospective multicenter study of 3707 patients with EMDs, 31 patients (0.8%) had a history of gastric surgery. Patient characteristics and POEM efficacy were compared between patients with and without previous gastric surgery. RESULTS: In patients with EMD after gastric surgery, age at EMD diagnosis was higher (72.0 years), male sex was predominant (90.3%), and the American Society of Anesthesiologists physical status score was higher (≥II, 48.4%). High-resolution manometry (HRM) findings did not reveal significant differences. In patients who underwent gastric surgery, atrophic gastritis was common (80.6%), and gastric cancer was the primary surgical indication (32.3%). Distal gastrectomy was performed in 28 patients (90.3%). POEM was effective (3.3% adverse events; 100% treatment success). The incidence rates of reflux esophagitis (RE) and symptomatic gastroesophageal reflux disease (GERD) were 60.0% and 16.7%, respectively, without significant intergroup differences, and severe RE was not observed in the long-term follow-up. Extended gastric myotomy was a risk factor for RE. CONCLUSION: Patients with gastric surgery often present severe disease manifestations; the surgical indication is mainly gastric cancer. HRM findings can be similarly used for diagnosis in patients with and without gastric surgery. POEM maintains safety and efficacy with acceptable RE and symptomatic GERD rates. To prevent RE, extended myotomy should be avoided.
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Acalasia del Esófago , Trastornos de la Motilidad Esofágica , Reflujo Gastroesofágico , Miotomía , Cirugía Endoscópica por Orificios Naturales , Neoplasias Gástricas , Humanos , Masculino , Anciano , Acalasia del Esófago/cirugía , Acalasia del Esófago/complicaciones , Neoplasias Gástricas/complicaciones , Japón/epidemiología , Cirugía Endoscópica por Orificios Naturales/efectos adversos , Trastornos de la Motilidad Esofágica/etiología , Trastornos de la Motilidad Esofágica/cirugía , Reflujo Gastroesofágico/etiología , Resultado del Tratamiento , Esfínter Esofágico Inferior/cirugíaRESUMEN
BACKGROUND: With the development of high-resolution manometry (HRM) and peroral endoscopy, more patients with esophageal motility disorders (EMDs) including achalasia are diagnosed and treated. The characteristics of Japanese patients with EMDs are unknown and should be elucidated. METHODS: A large-scale database analysis was performed at seven high-volume centers in Japan. EMDs between 2010 and 2019 were analyzed. RESULTS: A total of 1900 patients were diagnosed with treatment naïve achalasia on esophagography. A long disease history was related to the sigmoid and dilated esophagus, and patients' symptom severity declined as achalasia progressed to the sigmoid type. Among 1700 patients received starlet HRM, 1476 (86.8%) completed the examination. Long disease history and sigmoid achalasia were identified as risk factors for the failure of HRM examination. Type I achalasia was the most common type found on starlet HRM, and 45.1% of patients with achalasia had lower esophageal sphincter (LES) pressure within the normal range. Type III had a high age of onset and mild symptom severity, compared to the other two subtypes. Type III achalasia, esophagogastric outflow obstruction (EGJ-OO), jackhammer esophagus (JE), and diffuse esophageal spasm (DES) were relatively rare compared to type I-II achalasia. The clinical characteristics of EGJ-OO, JE, and DES were generally close to those of achalasia. CONCLUSION: This first large-scale database analysis indicates that more Japanese patients with achalasia are type I and have a normal range of LES pressure on starlet HRM. Failure of HRM is not rare; therefore, esophagography continuously has a complementary role in achalasia diagnosis.
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Acalasia del Esófago , Trastornos de la Motilidad Esofágica , Acalasia del Esófago/diagnóstico por imagen , Acalasia del Esófago/etiología , Trastornos de la Motilidad Esofágica/complicaciones , Trastornos de la Motilidad Esofágica/diagnóstico , Trastornos de la Motilidad Esofágica/epidemiología , Humanos , Japón/epidemiología , ManometríaRESUMEN
BACKGROUND: Thioredoxin reductase 1 (TXNRD1) and heme oxygenase-1 (HO-1) are both involved in the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and play key roles in antioxidant responses. In patients with esophageal squamous cell carcinoma (ESCC), the correlation between the expression of these two proteins and the therapeutic response to neoadjuvant chemoradiation therapy (NACRT), as well as the difference in their expression after chemoradiotherapy, remains unknown. METHODS: Proteins involved in the Nrf2 pathway were immunolocalized in carcinoma cells in ESCC patients on NACRT with 5-fluorouracil and cisplatin, followed by esophagectomy. The 8-hydroxydeoxyguanosine (8-OHdG) levels were used to quantify reactive oxygen species. The changes in immunoreactivity before and after NACRT (Δ) were assessed. RESULTS: Tumor reduction following NACRT was significantly attenuated in pre-therapeutic biopsy specimens associated with high HO-1 status. TXNRD1Δ, HO-1Δ, and 8-OHdGΔ were significantly different in the ineffective and effective groups. The overall survival was significantly lower in high Nrf2 and TXNRD1 groups. In addition, high TXNRD1 expression was an independent prognostic factor in the multivariate analysis of overall survival. CONCLUSIONS: The study findings indicate that HO-1 status in pre-therapeutic biopsy specimens could predict response to NACRT, and TXNRD1 status could predict overall survival of ESCC patients.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/patología , Hemo-Oxigenasa 1/genética , Hemo-Oxigenasa 1/uso terapéutico , Humanos , Factor 2 Relacionado con NF-E2/uso terapéutico , Terapia Neoadyuvante , Tiorredoxina Reductasa 1/genéticaRESUMEN
INTRODUCTION: Although teriparatide (TPTD) and exercise may improve osteoporosis, muscle atrophy, and fat metabolism during ageing, the effects of treatment with a combination of TPTD and exercise on these factors remain unclear. Therefore, this study examined the effects of TPTD and exercise on bone, skeletal muscle, and fat in ovariectomized and tail-suspended rats. MATERIALS AND METHODS: Seven-month-old female Wistar rats were ovariectomized and subjected to tail suspension. The rats were then randomized into one of the following four groups (n = 20/group) after 4 weeks: control group, treated with TPTD vehicle and no exercise; TPTD group (30 µg/kg TPTD, 3 days/week); Exercise group (treadmill at 12 m/min, 60 min/day, 5 days/week); and Combined group treated with TPTD and treadmill exercise. After 1 and 8 weeks of treatment, bone, skeletal muscle, and fat tissue parameters were evaluated. RESULTS: TPTD improved bone mineral density (BMD), bone structure, bone strength at the femoral metaphysis, and the percentage of skeletal muscle mass, and decreased the percentage of fat mass and the adipose volume in the bone marrow. Treadmill exercise increased BMD, bone strength of cancellous bone, and the percentage of skeletal muscle mass, and decreased the percentage of fat mass as seen on dual-energy X-ray absorptiometry. Furthermore, combined treatment significantly affected BMD, bone structure, and bone strength of cortical bone at the femoral diaphysis. CONCLUSION: TPTD or treadmill exercise improved bone, skeletal muscle, and fat mass. Combination therapy with TPTD and exercise had synergistic effects on BMD, structure, and bone strength in ovariectomized, tail-suspended rats.
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Adiposidad/efectos de los fármacos , Huesos/fisiología , Suspensión Trasera , Músculo Esquelético/fisiología , Ovariectomía , Condicionamiento Físico Animal , Teriparatido/farmacología , Absorciometría de Fotón , Animales , Biomarcadores/metabolismo , Fenómenos Biomecánicos/efectos de los fármacos , Peso Corporal , Densidad Ósea/efectos de los fármacos , Conservadores de la Densidad Ósea/farmacología , Huesos/diagnóstico por imagen , Huesos/efectos de los fármacos , Femenino , Fémur/diagnóstico por imagen , Fémur/efectos de los fármacos , Fémur/metabolismo , Humanos , Músculo Esquelético/efectos de los fármacos , Ratas Wistar , Teriparatido/administración & dosificación , Tibia/diagnóstico por imagen , Tibia/efectos de los fármacos , Tibia/fisiología , Microtomografía por Rayos XRESUMEN
BACKGROUND AND AIM: Achalasia is a rare disease, with an incidence of one in 100 000. Genetic factors and autoimmune involvement have been reported in its etiology, and their involvement is strongly suspected, especially in patients with familial achalasia and those with comorbid hereditary or autoimmune diseases. However, these special types of achalasia are rare, and their frequency and clinical characteristics remain unclear. METHODS: This retrospective, multicenter cohort study included Japanese patients with a diagnosis of achalasia, treated between 2010 and 2019 across six tertiary centers in Japan. The frequency and clinical characteristics of special types of achalasia, namely, familial achalasia, achalasia with a comorbid hereditary disease, and achalasia with a comorbid autoimmune disease, were retrospectively investigated using a large-scale multicenter database. RESULTS: During the study period, 1115 patients were treated for achalasia at six tertiary centers. Familial achalasia, achalasia with a comorbid hereditary disease, and achalasia with a comorbid autoimmune disease occurred in 7 (0.63%), 11 (0.99%), and 27 (2.4%) patients, respectively. Familial achalasia had a slightly younger age of onset (37.6 ± 12.1 years old) and a higher incidence in male patients (six patients; 85.7%). Down's syndrome was the most common hereditary comorbidity, and thyroid disease was the most common autoimmune comorbidity. CONCLUSIONS: We clarified the frequency and clinical characteristics of special types of achalasia. Although special types of achalasia are rare, these comorbidities should be considered when treating patients with achalasia.
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Enfermedades Autoinmunes , Acalasia del Esófago , Adulto , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/epidemiología , Estudios de Cohortes , Acalasia del Esófago/diagnóstico , Acalasia del Esófago/epidemiología , Acalasia del Esófago/genética , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: Muir-Torre syndrome (MTS), which accounts for a small subset (1-3 %) of Lynch syndrome (LS), is an autosomal dominant genetic disorder characterized by sebaceous gland or keratoacanthoma associated with visceral malignancies. Most families with MTS have pathogenic germline variants (PGV) in MSH2. Sarcomas are not common on the LS tumor spectrum, and sarcomas associated with MTS are extremely rare. CASE PRESENTATION: Here we report a myxofibrosarcoma of the abdominal wall in a 73-year-old man with a sebaceoma that occurred synchronically, leading to a diagnosis of MTS. The loss of MLH1 and PMS2 protein expression was detected in immunohistochemistry, and high-frequency microsatellite instability (MSI-H) was also confirmed. A germline genetic analysis revealed that he harbored the MLH1 PGV. CONCLUSIONS: This is the first case of MSI-H myxofibrosarcoma with MTS in an MLH1 PGV carrier. Although rare, we should recognize that sarcomas can be part of the spectrum of LS and MTS.
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BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a highly malignant neoplasm. The glucocorticoid (GC)-glucocorticoid receptor (GR) pathway plays pivotal roles in cellular response to various stresses of tumor cells, including chemotherapy. However, the status of the GC-GR pathway in ESCC, including its correlation with chemotherapeutic responses, is largely unknown. METHODS: GR, serum-and glucocorticoid-regulated kinase 1 (Sgk1), and N-myc down regulation gene 1 (NDRG1) were immunolocalized in 98 patients with ESCC who had undergone esophagectomy following neoadjuvant chemotherapy (NAC) with 2 courses of 5-fluorouracil + cisplatin. We also examined biopsy specimens before NAC in 42 cases and compared the results between those before and after NAC. RESULTS: Overall survival (OS) of the patients treated with surgery following NAC was significantly shorter in the group with high GR than that with low GR status (P = 0.0473). Both OS and disease-free survival (DFS) were significantly shorter in both Sgk1- and NDRG1-high groups than in the low groups (OS: Sgk1, P = 0.0055; NDRG1, P = 0.0021; DFS: Sgk1, P = 0.0240; NDRG1, P = 0.0086). Biopsy specimens before NAC showed significantly shorter DFS in the high Sgk1 group (P = 0.0095), while both OS and DFS were shorter in the high NDRG1 group (OS, P = 0.0233; DFS, P = 0.0006) than in the respective low groups. In the high NDRG1 group of biopsy specimens before NAC, the tumor reduction rate by NAC was significantly attenuated (P = 0.021). CONCLUSIONS: High GR, Sgk1, and NDRG1 statuses in ESCC after NAC was significantly associated with an overall worse prognosis, with no significant changes in their expression levels before and after NAC. Therefore, increased activity of the GC-GR pathway with enhanced induction of Sgk1 and NDRG1 in carcinoma cells play pivotal roles in tumor progression and development of chemo-resistance in patients with ESCC undergoing NAC.
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Antineoplásicos/uso terapéutico , Proteínas de Ciclo Celular/metabolismo , Neoplasias Esofágicas/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Proteínas Inmediatas-Precoces/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Receptores de Glucocorticoides/metabolismo , Cisplatino/uso terapéutico , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas de Esófago/metabolismo , Femenino , Fluorouracilo/uso terapéutico , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Terapia Neoadyuvante , Análisis de Supervivencia , Resultado del Tratamiento , Regulación hacia ArribaRESUMEN
BACKGROUND AND AIMS: Peroral endoscopic myotomy (POEM) is an available treatment modalities for achalasia. The reported efficacy of POEM in the only prospective multicenter study was 82%; however, a retrospective multicenter study in Japan reported a higher efficacy rate of 95%. The aim of this study was to prospectively verify treatment outcomes after POEM at multiple facilities in Japan. METHODS: This was a prospective single-arm trial of POEM for achalasia at 8 facilities in Japan between April 2016 and March 2018 to evaluate its safety and efficacy. Patients were re-evaluated at 3 months and up to 1 year after POEM. RESULTS: Among the 233 patients with achalasia who underwent POEM, procedure-related adverse events occurred in 24 patients (10.3%), none of whom required surgical intervention. In the 207 patients satisfying the inclusion criteria, the efficacy rate of POEM, defined by an Eckardt score ≤3 at 1 year, was 97.4% (95% CI, 95.3%-99.7%). The Eckardt score decreased significantly from 6.6 ± 2.0 preoperatively to 1.1 ± 1.1, 1 year after POEM. Postoperative reflux esophagitis, severe reflux esophagitis, and symptomatic GERD were reported in 54.2%, 5.6%, and 14.7%, respectively, and proton pump inhibitors were administered in 21.1%. CONCLUSIONS: Our prospective multicenter study in Japan showed greater efficacy of POEM for achalasia compared with the results of a previous prospective multicenter study. POEM is safe and highly effective for at least 1 year. (Clinical trial registration number: UMIN 000021550.).
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Acalasia del Esófago , Miotomía , Cirugía Endoscópica por Orificios Naturales , Acalasia del Esófago/cirugía , Humanos , Japón/epidemiología , Estudios Prospectivos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
INTRODUCTION: Postmenopausal osteoporosis and dyslipidemia are well-known skeletal and metabolic changes in middle-aged women. We investigated the effects of combined treatments with a selective estrogen receptor modulator (SERM) and exercise on bone and fat parameters in ovariectomized (OVX) rats. MATERIALS AND METHODS: Sixteen-week-old female Sprague-Dawley rats underwent bilateral ovariectomy, and rats were randomized to BZA (bazedoxifene at 0.3 mg/kg/day), Exe (treadmill exercise at 12-15 m/min, 60 min/day, 5 days/week), Comb (BZA and Exe), and Cont (control treated with vehicle and no exercise) groups 8 weeks after ovariectomy. After 4 or 8 weeks of treatment, bone mineral density (BMD) of the total femur and lumbar spine and whole-body percentage fat mass were determined by dual-energy X-ray absorptiometry, and mechanical testing of the femoral shaft, and bone and fat histomorphometric analyses of the proximal tibia were performed. RESULTS: Treadmill exercise had decreased bone marrow adipocytes from 4 weeks of treatment and whole-body percentage fat mass at 8 weeks. BZA increased BMD at the lumbar spine and decreased the whole-body percentage fat mass from 4 weeks and bone marrow adipocytes at 8 weeks. Combination therapy increased BMD for the lumbar spine and decreased bone marrow adipocytes and whole-body percentage fat mass from 4 weeks. CONCLUSION: Combination therapy with BZA and exercise appears effective to improve bone and fat parameters in OVX rats.