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Purpose: The quality and bias of annotations by annotators (e.g., radiologists) affect the performance changes in computer-aided detection (CAD) software using machine learning. We hypothesized that the difference in the years of experience in image interpretation among radiologists contributes to annotation variability. In this study, we focused on how the performance of CAD software changes with retraining by incorporating cases annotated by radiologists with varying experience. Methods: We used two types of CAD software for lung nodule detection in chest computed tomography images and cerebral aneurysm detection in magnetic resonance angiography images. Twelve radiologists with different years of experience independently annotated the lesions, and the performance changes were investigated by repeating the retraining of the CAD software twice, with the addition of cases annotated by each radiologist. Additionally, we investigated the effects of retraining using integrated annotations from multiple radiologists. Results: The performance of the CAD software after retraining differed among annotating radiologists. In some cases, the performance was degraded compared to that of the initial software. Retraining using integrated annotations showed different performance trends depending on the target CAD software, notably in cerebral aneurysm detection, where the performance decreased compared to using annotations from a single radiologist. Conclusions: Although the performance of the CAD software after retraining varied among the annotating radiologists, no direct correlation with their experience was found. The performance trends differed according to the type of CAD software used when integrated annotations from multiple radiologists were used. [ABSTRACT FROM AUTHOR]

Objective: Despite being a less-invasive procedure, esophagectomy can cause severe infectious complications, such as pneumonia and anastomotic leakage. Herein, we aimed to clarify the inflammatory characteristics of pneumonia/anastomotic leakage after esophagectomy by assessing the difference between the postoperative trends of serum C-reactive protein (CRP) and procalcitonin (PCT) levels in patients with pneumonia/anastomotic leakage using the values on the consecutive postoperative day (POD). Methods: This study included 439 patients who underwent minimally invasive esophagectomy. Serum CRP and PCT levels were measured on PODs 1–7, 10, and 14. Pneumonia and anastomotic leakage were defined as Clavien–Dindo grades ≥ 2. Results: Pneumonia and anastomotic leakage occurred in 96 and 51 patients, respectively. The CRP and PCT levels peaked on POD 3 (11.6 ± 6.8 mg/dL) and POD 2 (0.69 ± 2.9 ng/mL), respectively. Between PODs 3 and 14, CRP levels were significantly higher in patients with pneumonia and anastomotic leakage than in those without complications (P < 0.001). Between PODs 3 and 14, PCT levels were significantly higher in patients with pneumonia; however, on most PODs, there were no significant differences in PCT levels between patients with and without anastomotic leakage. Conclusion: Inflammatory reactions caused by pneumonia may be more intense than those caused by anastomotic leakage after esophagectomy. Postoperative trends in serum CRP and PCT levels may vary depending on the complication type. Pneumonia and anastomotic leakage after esophagectomy can be potentially distinguished by the postoperative trend of PCT values before detailed examinations, such as computed tomography and endoscopy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Studying multiple properties of a material concurrently is essential for obtaining a comprehensive understanding of its behavior and performance. However, this approach presents certain challenges. For instance, simultaneous examination of various properties often necessitates extensive experimental resources, thereby increasing the overall cost and time required for research. Furthermore, the pursuit of desirable properties for one application may conflict with those needed for another, leading to trade-off scenarios. In this study, we focused on investigating adhesive joint strength and elastic modulus, both crucial properties directly impacting adhesive behavior. To determine elastic modulus, we employed a non-destructive indentation method for converting hardness measurements. Additionally, we introduced a specimen apparatus preparation method to ensure the fabrication of smooth surfaces and homogeneous polymeric specimens, free from voids and bubbles. Our experiments utilized a commercially available bisphenol A-based epoxy resin in combination with a Poly(propylene glycol) curing agent. We generated an initial dataset comprising experimental results from 32 conditions, which served as input for training a machine learning model. Subsequently, we used this model to predict outcomes for a total of 256 conditions. To address the high deviation in prediction results, we implemented active learning approaches, achieving a 50% reduction in deviation while maintaining model accuracy. Through our analysis, we observed a trade-off boundary (Pareto frontier line) between adhesive joint strength and elastic modulus. Leveraging Bayesian optimization, we successfully identified experimental conditions that surpassed this boundary, yielding an adhesive joint strength of 25.2 MPa and an elastic modulus of 182.5 MPa. [ABSTRACT FROM AUTHOR]

Background: Anastomotic leakage after esophagectomy is a common complication. Laser Doppler flowmetry (LDF) can quantitatively evaluate the blood flow in the gastric conduit. Methods: A total of 326 patients who underwent thoracoscopic/robot‐assisted esophagectomy followed by gastric conduit reconstruction and end‐to‐side anastomosis were enrolled. We divided the gastric conduit into zones I (dominated by the right gastroepiploic vessels), II (dominated by the left gastroepiploic vessels), and III (perfused with short gastric vessels). Before pulling up the gastric conduit to the neck, LDF values were measured at the pylorus, the border between zones I and II (zone I/II), the border between zones II and III (zone II/III), and the gastric conduit tip (tip). The blood flow ratio was calculated as the LDF value divided by the LDF value at the pylorus. Results: Anastomotic leakage developed in 32 of 326 patients. Leakage was significantly associated with the blood flow ratio at the tip (p < 0.001), but not at zone I/II, zone II/III, and the anastomotic site. The receiver‐operating characteristic curve analysis identified an anastomotic leakage cutoff ratio of 0.41 (at the tip). A multivariate Cox analysis showed that a blood flow ratio <0.41 at the tip was an independent risk factor for anastomotic leakage (p < 0.001). Conclusion: Anastomotic leakage after esophagectomy was significantly associated with the blood flow ratio at the tip of the gastric conduit. Preservation of the blood supply to the tip via the gastric wall might contribute to a decreased incidence of anastomotic leakage. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The mechanical properties of polyurethane compounds were experimentally investigated by changing the composition of their components. Polyol components (polyoxypropylene glycol: PPG, polyoxytetramethylene glycol: PTMG, and polycarbonatediol: PCD) were mixed with monomeric methylene diphenyl diisocyanate to synthesize polyurethane pre-polymer, mixed with chain extenders (1,4'-butanediol: 1,4'-BD or dimethylthiotoluene diamine: DMTDA), and cured, to prepare four types of polyurethane resins. Tensile tests were conducted using a mechanical testing machine with a strain rate of approximately 0.3 s−1 and a hydraulic high-speed tensile testing machine with a strain rate of approximately 500 s−1. The temperature was controlled to be −40°C, −10°C, or 25°C. When PTMG was used as the polyol, the stress-strain relationship was less sensitive to temperatures and loading rates, and the material properties exhibited a relatively good balance between elongation and strength. Additionally, the use of 1,4'-BD as a chain extender resulted in higher elongation and lower strength than the use of DMTDA. Conversely, the stress-strain relationship was dramatically altered by the test conditions when PPG and PCD were used as the polyol and embrittlement under a combination of low temperature and high strain rate was confirmed. Furthermore, there were certain compositional combinations that exhibit necking at low temperatures. [ABSTRACT FROM AUTHOR]

Machine learning is extensively used in material research and development, including adhesion technology. However, it requires a large dataset to train the models for optimizing, developing, and designing new adhesives. This study proposes a novel testing machine that enables quick high-throughput measurements of the shear strength of adhesively bonded joints. A small cylindrical butt shear joint (BSJ) specimen placed in a holder was pushed by a metal specimen pusher until failure; during this process, the force and displacement were recorded. This testing machine can be used to quickly conduct the measurement by simply placing the specimen in a holder and pushing it. A comparison of the average shear strength measured by this method and that measured by single-lap shear tests, coupled with stress analysis using finite element simulation suggested that the proposed method can measure the shear strength more accurately, where a higher level of pure shear can be achieved in the adhesive layers with a lower degree of stress concentration and smaller peeling stress at the extremities of the adhesives. This indicates that the shear strength of adhesively bonded joints can be measured quickly using the proposed testing method, thereby facilitating the development of new adhesives using machine learning. [ABSTRACT FROM AUTHOR]

Giant cell tumor of bone (GCTB) is a rare bone tumor with osteolytic features, composed of stromal cells with a monotonous appearance, macrophages, and osteoclast-like giant cells. GCTB is commonly associated with a pathogenic mutation in the H3-3A gene. While complete surgical resection is the standard cure for GCTB, it often results in local recurrence and, rarely, metastasis. Thus, an effective multidisciplinary treatment approach is necessary. Although patient-derived cell lines is an essential tool for investigating novel treatment strategies, there are only four GCTB cell lines available in public cell banks. Therefore, this study aimed to establish novel GCTB cell lines and successfully created NCC-GCTB6-C1 and NCC-GCTB7-C1 cell lines from two patients' surgically removed tumor tissues. These cell lines exhibited H3-3A gene mutations, consistent proliferation, and invasive properties. After characterizing their behaviors, we performed high-throughput screening of 214 anti-cancer drugs for NCC-GCTB6-C1 and NCC-GCTB7-C1 and integrated their screening data with those of NCC-GCTB1-C1, NCC-GCTB2-C1, NCC-GCTB3-C1, NCC-GCTB4-C1, and NCC-GCTB5-C1 that we previously established. We identified histone deacetylase inhibitor romidepsin as a possible treatment for GCTB. These findings suggest that NCC-GCTB6-C1 and NCC-GCTB7-C1 could be valuable tools for preclinical and basic research on GCTB. [ABSTRACT FROM AUTHOR]

Wood, as one of the important materials to make music instruments, has many drawbacks, including its sensitivity to changes in temperature and humidity, the lack of available wood resources, the significant variability of wood, and the demanding level of expertise needed. New materials such as composites are needed to be developed to be substitutes for woods. In this study, a finite element (FE)-based machine learning method is proposed to design a xylophone using sandwich beam as a substitute to wood. A finite element (FE) procedure based on a higher order layer-wise beam theory is developed. In addition, a machine learning model is developed to predict the natural frequencies of sandwich beams. The model is designed and trained to consider the results obtained from developed FE procedure as input and predict accurate natural frequencies. The results recorded from this model are compared with the experimental values. Then, inverse analysis is performed to design sandwich beam of different geometric sizes for constrained natural frequencies using machine learning. [ABSTRACT FROM AUTHOR]

Adhesive joints are degraded when exposed to moist conditions, making it essential to assess the permeation distance of absorbed moisture. However, monitoring the water penetration in the adhesive layer is challenging because the adhesive layer is sandwiched between the adherends. To overcome this difficulty, we proposed a new monitoring system using fiber‐type near‐infrared spectroscopy (NIRS), and the moisture distribution at the joint was successfully observed by introducing quartz glass as one side of the substrate. First, the change in the absorbance spectra owing to water absorption by an epoxy adhesive was investigated by immersing epoxy‐coated aluminum alloy plates in temperature‐controlled water. It was found that the water content can be evaluated by monitoring the change in the peak intensity appearing around 1900–1950 nm. Next, water penetration into the adhesive layer sandwiched between the quartz glass and aluminum alloy was investigated by scanning the surface. The water permeation distance was found to change with temperature. Under the 23°C immersion condition, approximately 2.5 mm of water penetration was observed after 8 weeks. Because the simulation results using Fick's law of diffusion showed similar trends, it was experimentally confirmed that Fickian diffusion dominates the water distribution in the adhesive layer. [ABSTRACT FROM AUTHOR]

Musculocontractural Ehlers–Danlos syndrome (mcEDS) is a heritable connective tissue disorder characterized by multiple congenital malformations and progressive connective-tissue-fragility-related manifestations in the cutaneous, skeletal, cardiovascular, visceral, ocular, and gastrointestinal systems. It is caused by pathogenic variants in the carbohydrate sulfotransferase 14 gene (mcEDS-CHST14) or in the dermatan sulfate epimerase gene (mcEDS-DSE). As gastrointestinal complications of mcEDS-CHST14, diverticula in the colon, small intestine, or stomach have been reported, which may lead to gastrointestinal perforation, here, we describe sisters with mcEDS-CHST14, who developed colonic perforation with no evidence of diverticula and were successfully treated through surgery (a resection of perforation site and colostomy) and careful postoperative care. A pathological investigation did not show specific abnormalities of the colon at the perforation site. Patients with mcEDS-CHST14 aged from the teens to the 30s should undergo not only abdominal X-ray photography but also abdominal computed tomography when they experience abdominal pain. [ABSTRACT FROM AUTHOR]

Conducting displacement‐controlled fatigue double cantilever beam tests of a structural acrylic adhesive, two different slopes were observed in the fatigue crack growth (FCG) relationship of the FCG rate versus the strain energy release rate (SERR) parameters depending on the loading conditions. Because fatigue is a two‐parameter problem where stress waveforms contain cyclic and monotonic terms, the contribution of each term toward FCG needs to be clarified. Therefore, each slope was explained using SERR with load range and mean load. In addition, cases were observed where the slope changed with an increasing number of cycles. Accordingly, the FCG rate changes. Understanding the phenomenon is important to estimate the crack position from an engineering point of view. Therefore, FCG was categorized into three types using amplitude and mean displacement. After a sufficient number of fatigue cycles, amplitude played a more dominant role than R‐ratio or mean displacement to determine crack location. Highlights: Two different slopes are observed in the fatigue crack growth (FCG) relationship.Periodic and mean loads are determined as the controlling factors for different slopes.Amplitude versus mean displacement plot is proposed to classify the FCG relationship. [ABSTRACT FROM AUTHOR]

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 of ≥ 4 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 (4.1 %) 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, 95 %CI 0.62–0.72) and calibration (slope 1.15, 95 %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 < 5 %) and high risk (9–22 points; ≥ 5 %) groups. The proportions of clinical failure for the categories were stratified according to the mid-term outcomes (log-rank test, P < 0.001). Conclusions This risk scoring system can predict the clinical failure of POEM preoperatively and provide useful information when making treatment decisions. [ABSTRACT FROM AUTHOR]

Background: Killian–Jamieson diverticulum, which is a relatively rare pharyngoesophageal diverticulum, is difficult to distinguish from Zenker's diverticulum. Because major points of the relevant surgical procedures for these two entities differ, it is important to make an accurate diagnosis. We herein report a case of Killian–Jamieson diverticulum initially diagnosed as Zenker's diverticulum. Case presentation: A 56-year-old man complaining of discomfort during swallowing was diagnosed with pharyngoesophageal diverticulum. He was initially diagnosed with Zenker's diverticulum before surgery, but the diverticulum actually arose from the left side of the esophageal wall, at the level of the cricoid cartilage and below the cricopharyngeal muscle. We therefore ultimately diagnosed this case as Killian–Jamieson diverticulum during surgery, and were able to preserve the muscle above the diverticulum, which would normally have to be cut when treating a case of Zenker's diverticulum. Conclusion: To make an accurate diagnosis, clinical and surgical findings are important to consider, including the location of the diverticulum and the relationship between the diverticula and cricopharyngeal muscles or between the diverticula, thyroid cartilage and cricoid cartilage. [ABSTRACT FROM AUTHOR]

Double cantilever beam (DCB) tests were conducted by immersing the specimens in temperature-controlled water while applying a creep load using a spring. By introducing a data reduction scheme to the spring-loaded DCB test method, it was confirmed that only a single parameter measurement was sufficient to calculate the energy release rate (ERR). Aluminum alloy substrates bonded with an epoxy adhesive were used, and DCB tests were performed by changing the initial load values, spring constants, and immersion temperatures for two types of surface treatment. The initial applied load and spring constant had no effect on the ERR threshold. In contrast, the threshold decreased with the increasing immersion temperature, but even in the worst case, it was 15% of the critical ERR in the static tests. Using the creep crack growth relationship, it was revealed that there were three phases of creep immersion crack growth in the adhesive joints, and each phase was affected by the temperature. The spring-loaded DCB test method has great potential for investigating the combined effects of creep, moisture, and temperature, and this study has demonstrated the validity of the test method. The long-term durability of adhesive joints becomes increasingly important, and this test method is expected to become widespread. [ABSTRACT FROM AUTHOR]

Pleomorphic liposarcoma (PLPS) is a highly malignant subtype of liposarcoma. It is histologically characterized by the presence of pleomorphic lipoblasts and can be accompanied by morphological foci that demonstrate differentiation to other histological lineages. PLPS is rare and accounts for only 5% of all liposarcomas. PLPS exhibits poor prognosis; distant metastases develop in 30–50% of patients after curative surgical resection, tumor-associated mortality occurs in up to 50% of patients, and effective chemotherapies for PLPS have not been established. The histological accompaniment of other morphological foci is an important prognostic factor for PLPS, and the development of chemotherapies for PLPS considering the histological morphology is necessary. Patient-derived cancer cell lines are critical tools for basic and pre-clinical research to understand diseases and develop chemotherapies. However, only two PLPS-derived cell lines have been reported, and their donor tumor specimens did not histologically accompany morphological foci other than lipoblasts. Thus, there is a need to establish patient-derived PLPS cell lines from various histological morphologies. Here, we report a novel PLPS cell line from a tumor specimen that histologically accompanied pleomorphic and bone-forming foci, and named it NCC-PLPS2-C1. NCC-PLPS2-C1 cells demonstrated constant proliferation, spheroid formation, and invasion capability in vitro. Screening of antitumor agents in NCC-PLPS2-C1 cells showed that bortezomib, romidepsin, and trabectedin were effective against NCC-PLPS2-C1. In conclusion, we report the first PLPS cell line from a tumor specimen that was morphologically accompanied by pleomorphic and born-forming foci. We believe that NCC-PLPS2-C1 will be useful for the development of novel chemotherapies for PLPS. [ABSTRACT FROM AUTHOR]

Myxofibrosarcoma (MFS) is a rare and aggressive mesenchymal malignancy characterized by complex karyotypes with heterogeneous clinical features. The standard treatment for primary MFS is curative resection; however, the utility of systemic chemotherapy and radiotherapy has not been established. Although patient-derived cancer cell lines are a key bioresource for developing novel therapies, the number of MFS cell lines available from public cell banks is limited by the rarity of the disease, and large-scale drug screening has not yet been performed. To address this issue, we aimed to establish and characterize a novel MFS cell line. We successfully established a cell line, NCC-MFS6-C1, which harbors genetic abnormalities common in MFS and exhibits aggressive phenotypes such as continuous growth, spheroid formation, and invasion in tissue culture conditions. We performed drug screening using NCC-MFS6-C1 along with five MFS cell lines established in our laboratory and clarified the response spectrum of 214 existing anticancer agents. We found that two anticancer agents, gemcitabine and romidepsin, showed considerable antiproliferative effects, and these observations were concordant with the findings of our previous report, in which these agents attenuated the proliferation of five previously reported MFS cell lines. We conclude that NCC-MFS6-C1 is a useful resource for studying MFS. [ABSTRACT FROM AUTHOR]

Malignant rhabdoid tumor (MRT) is a sarcoma histologically characterized by rhabdoid cells and genetically characterized by loss of function of the chromatin remodeling complex SWI/SNF induced by SMARCB1 gene deficiency. MRT mainly occurs in children, may arise in various locations, but is predominantly in the central nervous system (CNS) and kidney. Although MRT exhibits poor prognosis, standard treatment has not yet been established due to its extreme rarity. Patient-derived cancer cell lines are critical tools for basic and pre-clinical research in the development of chemotherapy. However, none of the MRT cell lines was derived from adult patients, and only one cell line was derived from the MRT of a soft tissue, despite the clinical behavior of MRT varying according to patient age and anatomic site. Herein, we reported the first cell line of MRT isolated from the soft tissue of an adult patient and named it NCC-MRT1-C1. NCC-MRT1-C1 cells showed a biallelic loss of the SMARCB1 gene. NCC-MRT1-C1 cells demonstrated rapid proliferation, spheroid formation, invasion capability in vitro, and tumorigenesis in nude mice. Screening of antitumor agents in NCC-MRT1-C1 cells resulted in the identification of six effective drugs. In conclusion, we report the first MRT cell line from the soft tissue of an adult patient. We believe that NCC-MRT1-C1 is a useful tool for developing novel chemotherapies for MRT. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 (64.9 %). Age ≥ 65 years (risk ratio [RR] 0.85), male sex (RR 1.11), posterior myotomy (RR 1.12), esophageal myotomy > 10 cm (RR 1.12), and gastric myotomy > 2 cm (RR 1.17) were independently associated with reflux esophagitis. Severe reflux esophagitis was diagnosed in 219 patients (7.5 %). Age ≥ 65 years (RR 1.72), previous treatments (RR 2.21), Eckardt score ≥ 7 (RR 0.68), sigmoid-type achalasia (RR 1.40), and esophageal myotomy > 10 cm (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 (P = 0.03) than after 1 year (P = 0.08). Symptomatic GERD was present in 458 patients (15.9 %). Symptom duration ≥ 10 years (RR 1.28), achalasia diagnosis (RR 0.68), integrated relaxation pressure ≥ 26 (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 (P = 0.04), particularly in PPI users (P < 0.001). 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Oral administration of cystine and theanine (CT) increases glutathione levels to modulate the inflammatory response, which has yet to be sufficiently explored for patients' recovery and early rehabilitation. We planned a randomized, double-blind, placebo-controlled trial to determine whether perioperative oral administration of CT promotes recovery after esophagectomy. Patients were randomized into either CT or placebo groups, who received preoperative and postoperative treatments for 4 and 13 days, respectively. The main outcome measures were triaxial accelerometer readings, inflammation indicators, a 6 min walk test (6MWT), and a quality of life questionnaire (QoR-40). The study involved 32 patients. Although the CT group (n = 16) showed better patient activity across the investigated period, there was no significant difference between the two groups. However, white blood cell count on postoperative days (POD) 2 and 10, neutrophil count (POD 2, 7, and 10), and C-reactive protein level (POD 13) in the CT group were significantly lower than in the placebo group. Furthermore, 6MWT on POD 7 and QoR-40 on POD 13 were significantly higher in the CT group than those in the placebo group. This study suggests that perioperative administration of CT may contribute to early recovery and rehabilitation after esophagectomy via suppression of inflammatory response. [ABSTRACT FROM AUTHOR]

Simple Summary: The neuroendocrine differentiation of tumors is considered to influence the tumor microenvironment through the secretion of various hormones or growth factors. However, cases of neuroendocrine and non-neuroendocrine neoplasms are difficult to compare because of the potential differences in systemic and local immune environments. The analysis of mixed neuroendocrine non-neuroendocrine neoplasms, in which neuroendocrine and non-neuroendocrine components are present in the same tumor, could provide important insights into the effects of neuroendocrine differentiation on tumor microenvironments. However, to the best of our knowledge, this has not been reported yet. Here, we compared the status of the tumor tissue microenvironment, including the infiltrating lymphocytes present, in the neuroendocrine and non-neuroendocrine areas of the same tumor. Factors related to neoangiogenesis and the suppression of tumor immune reactions were more abundant in neuroendocrine than in non-neuroendocrine areas. Therefore, neuroendocrine and non-neuroendocrine tumors differ with respect to the characteristics of both tumor cells and the tumor microenvironment. The tumor microenvironment is considered to play a pivotal role in various human malignancies. Neuroendocrine and non-neuroendocrine neoplasms are considered to have different tumor microenvironments. However, owing to differences in the systemic and/or local immune statuses, tumor microenvironments in different patients may be difficult to compare. Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs), although rare, could be useful for exploring the effects of neuroendocrine differentiation on the tumor microenvironment, because both neuroendocrine and non-neuroendocrine components are present in the same tumor. Here, we examined 33 cases of histologically confirmed MiNENs and evaluated the influence of neuroendocrine differentiation on the tumor microenvironment by comparing tumor-infiltrating lymphocytes, tumor-associated macrophages, and other relevant factors in the two components the same tumor. The immunoreactivity of those examined above was evaluated quantitatively. The values of vasohibin-1-positive density (p < 0.0001) and immunoreactivity (p < 0.0001) (representing the neoangiogenesis status) were significantly higher in neuroendocrine as compared to non-neuroendocrine areas of the same tumors. In addition, the Foxp3/CD8 (p = 0.0717) and the PD-1/CD8 ratios (p = 0.0176) (representing tumor immunity suppression) tend to increase in neuroendocrine carcinomas. Immunoreactivity of CD163, a marker of M2-like macrophages, was also higher in the neuroendocrine areas. Our findings indicate that neuroendocrine and non-neuroendocrine tumors differ from each other with respect to the characteristics of both tumor cells and the tumor microenvironment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: As the population ages, the proportion aged ≥75 years is expected to increase. Many studies on peroral endoscopic myotomy (POEM) as treatment for esophageal achalasia have already been reported; however, few studies have been designed on patients aged ≥75 years. The purpose of this study is to describe the characteristics of esophageal achalasia in patients >75 years and to evaluate the outcomes of POEM. Methods: This study included 121 patients who underwent POEM for esophageal achalasia, which was divided into the geriatric (n = 18) group aged ≥75 and the young (n = 103) group ≤74 years. The characteristics of esophageal achalasia and the short‐term outcomes after POEM in the geriatric group compared with the young group were retrospectively investigated. Results: The median age of the geriatric group was 78 years, and two patients were initially diagnosed with refractory pneumonia, and esophageal achalasia was initially overlooked. The preoperative Eckardt score of the geriatric group was significantly lower than that of the young group (4 vs. 6, P = 0.007), particularly in the regurgitation score. The Eckardt score and integrated relaxation pressure of both groups were significantly improved after POEM (P < 0.001). There were no cases of perioperative complications in the geriatric group. Conclusions: POEM for esophageal achalasia is a safe and effective treatment even in geriatric patients >75 years of age. In geriatric patients with recurrent or intractable pneumonia, it is important to rule out esophageal achalasia. Geriatr Gerontol Int 2021; 21: 788–793. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Esophageal achalasia causes dysphagia following impaired relaxation of the lower esophageal sphincter due to the degeneration of Auerbach's plexus in the esophageal smooth muscle. Recently, peroral endoscopic myotomy (POEM) has become one of the preferred treatment options for esophageal achalasia. However, pathomorphological changes after POEM have not been well examined. Case presentation: A 65-year-old man with a history of POEM for esophageal achalasia was diagnosed with clinical stage II (cT2-N0-M0) thoracic esophageal squamous cell carcinoma and was consequently treated with neoadjuvant chemotherapy followed by thoracoscopic esophagectomy. Intraoperatively, the esophagus appeared dilated, reflecting esophageal achalasia; however, fairly slight fibrous adhesions were observed between the esophagus and the pericardial surface despite previously performed POEM via an anterior incision. Histopathological examination revealed esophageal wall thickening, edema, and fibrosis extending from the lamina propria to the submucosa. Besides, the majority of the inner layer and some proportion of the outer layer of the muscularis propria were found to be missing or atrophic at the esophagogastric junction (EGJ). No ganglion cells could be detected at the Auerbach's plexus. Conclusions: The previous history of POEM did not affect circumferential mediastinal periesophageal dissection during thoracoscopic esophagectomy. Nevertheless, a large proportion of the inner layer of the muscularis propria at the EGJ level seemed to have become lost or atrophic because of the POEM procedure. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The patient was a 44-year-old man with a history of schizophrenia. He had a history of esophageal dysphagia and vomiting and presented with sudden strong epigastric pain. He was taken to a medical emergency center in a state of septic shock. Computed tomography revealed a left thoracic abscess, and esophageal rupture was suspected. He was referred to our department for treatment. Gastrointestinal series and gastrointestinal endoscopy revealed marked esophageal dilation and strong contraction of the lower esophageal sphincter. We, therefore, diagnosed the patient with empyema thoracis secondary to aspiration pneumonia due to esophageal achalasia. Conservative treatment with antibiotics and computed tomography-guided chest drainage was initiated, but the inflammation persisted. Thus, we successfully performed a per-oral endoscopic myotomy to manage achalasia symptoms. [ABSTRACT FROM AUTHOR]

Background: Achalasia has been reported to be associated with esophageal cancers (ECs). However, owing to the rarity of achalasia, details of achalasia-related ECs are not well investigated. Method: The incidence of ECs in Japanese patients with achalasia and achalasia-related esophageal motility disorders (EMDs) was estimated, and risk factors for achalasia-related ECs were determined. Characteristics of ECs and treatment courses were also analyzed. Results: Between 2010 and 2019, 2714 Japanese patients with achalasia and achalasia-related EMDs were recorded in 7 high-volume centers; 24 patients (21 men, 3 women) developed ECs. The incidence of ECs was estimated at 0.078 and 0.28 per 100 person-years from the onset and the diagnosis of disease, respectively. Kaplan–Meier estimate suggested that, in addition to a long history of achalasia, advanced age, male sex, and regular alcohol consumption were statistically significant risk factors for EC development. A prevalence of 40 ECs (12.5% multiple lesions, and 22.7% metachronal lesions) was also noted, predominantly distributed over the thoracic esophagus. All were histologically diagnosed as squamous cell carcinoma. Superficial ECs were successfully treated with endoscopic treatment in all cases, except one. Achalasia-related Barret esophagus was extremely rare, and Barret adenocarcinoma was not detected in our cohort. Conclusion: The high relative risk of ECs was clarified in Japanese achalasia patients, although the absolute risk remained low. Therefore, surveillance endoscopy may be recommended in limited patients with several aforementioned risk factors determined. Superficial cancer can be treated with endoscopic treatment. Multiple and metachronal ECs should be screened. [ABSTRACT FROM AUTHOR]

Although adhesive-adherend interfaces play an important role in improving adhesive joint strength, their observation is a challenging task. If the adhesive and adherend can be clearly separated, the interface can be observed directly. Because this was fortunately achieved with the combination of a second-generation acrylic adhesive and several plastics, the differences in the formation of sea-island structures at interfaces was verified as related to adhesive strength. Phase mapping, stiffness measurements, and thermal analysis were conducted with atomic force microscopy (AFM) to investigate the physical properties of the sea-island structures. The internal adhesive structure observed by AFM was in good agreement with the transmission electron microscopy analyses. The structure of the adhesive-adherend interface that showed a good bonding strength was similar to the internal structure, forming a large acrylic-rich island and rubber-rich sea. In the case of plastics with low surface energies, however, the interface formed a distinctive structure with small acrylic islands in a rubber sea. The difference in the formation of the sea-island structure is considered to be related to the wettability of the adhesive to the adherends, and it was revealed that a stronger interface corresponds to a structure more closely resembling that of the inside. [ABSTRACT FROM AUTHOR]

Background Although the outcome of patients with recurrent esophageal cancer following radical esophagectomy is extremely poor, long-term survival can be achieved with multimodal therapy, including surgical resection of the recurrent lesion. Developing a treatment strategy is a critical issue; therefore, we examined the indications and optimal timing for surgical treatment in patients with recurrence. Methods A total of 184 patients with recurrent esophageal cancer after radical esophagectomy were studied between 2001 and 2015, with a focus on surgical resection. Results The first recurrence site was the lymph nodes (124 cases; 67%) [neck (35; 19%), mediastinum (82; 45%), abdomen (35; 19%)], lung (36; 20%), liver (32; 17%), pleura (18; 10%), bone (13; 7%), etc. Second-line treatment following recurrence was surgery (8 cases), chemoradiotherapy (89 cases), chemotherapy (64 cases), and best supportive care (23 cases). Patients with single organ or solitary recurrence and recurrence more than 8 months after surgery had better prognoses. All the surgical cases had single-site recurrence (lung-3, cervical lymph nodes-3, colon-1, and brain-1). Good prognosis was expected for the patients with lung or cervical lymph node recurrence. Conclusion Surgical treatment for recurrent esophageal cancer following radical esophagectomy was considered beneficial for the recurrence of cervical lymph node or lung metastasis of solitary lesions at least 8 months after esophagectomy. Immune checkpoint inhibitors have recently been indicated for esophageal cancer and expected for improving prognosis, and the role of surgery in multidisciplinary treatment for metastatic recurrence needs repeated investigation. [ABSTRACT FROM AUTHOR]

Background: Per-oral endoscopic myotomy (POEM) is an endoscopic procedure whereby the esophageal muscle is incised in order to lower the lower esophageal sphincter (LES) pressure. Since the time it was first performed in 2008 and subsequently reported on in 2010 by Inoue et al., POEM has been shown to be safe and effective for straight type of achalasia. On the other hand, the efficacy of POEM had been controversial for patients with achalasia of the sigmoid type, in which a high LES pressure is accompanied by morphological changes, including dilation, acute angulation, and rotation. The aim of this study is to evaluate the safety and efficacy of POEM in patients with sigmoid type of achalasia.Methods: Between May 2015 and December 2017, 16 patients with a sigmoid type of achalasia underwent POEM in our institute. The POEM procedure was the same as that for the straight type of achalasia. The double-scope technique was used to check the distal end of the submucosal tunnel from the gastric side. The primary endpoint was improvement of Eckardt score at 2 months after POEM. The secondary endpoints comprised operating time, change in the esophageal angulation, and adverse events.Results: All patients underwent POEM without severe adverse events. The respective parameters before and after POEM significantly differed in terms of mean (SD) Eckardt score [4.9 (2.0) vs. 0.4 (0.6), p < 0.01], LES pressure [19.4 (10.2) vs. 9.2 (6.4), p < 0.01], and integrated relaxation pressure [17.6 (9.2) vs. 7.9 (5.5), p < 0.01]. The average operation time was 94.7 ± 31.4 min. The average esophageal angulation was 88.4° ± 23.1° before POEM and 109.5° ± 16.7° after POEM (p < 0.01). Four patients had postoperative complications that were treated conservatively.Conclusions: POEM can improve both LES pressure and esophageal angulation in patients with sigmoid achalasia. [ABSTRACT FROM AUTHOR]

Background: While anastomotic leakage, recurrent laryngeal nerve paralysis, and pneumonia are well-known complications of esophagectomy, the incidence of hiatal hernia after esophagectomy for carcinoma has been reported to only be between 0.6 and 10%. We report a very rare case of hiatal hernia with transverse colon rupture in the mediastinum after esophagectomy in a 65-year-old woman. Case presentation: The patient underwent definitive chemoradiotherapy for clinical stage IIA esophageal squamous cell carcinoma and salvage esophagectomy with gastric tube reconstruction through a posterior mediastinum route for residual carcinoma. Three years after the initial surgery, two metastatic nodules in the lateral and posterior segments of the liver were detected on follow-up CT and were treated with oral anticancer drugs. After 6 months, the patient was readmitted for anorexia. Upon admission, computed tomography revealed an ileus caused by a hiatal hernia. Emergent operative repair was performed; an incarcerated herniation of the transverse colon was perforated in the mediastinum, and partial transverse colon resection and colostomy were performed. Intensive care was required to control septic shock after surgery, and the patient was discharged on the 53rd postoperative day. Conclusions: Cases of hiatal hernia with digestive tract prolapsing into the mediastinum after esophagectomy with reconstruction through posterior mediastinum are rare but potentially life-threatening complications. [ABSTRACT FROM AUTHOR]

The plastic zone at the crack front of an adhesively bonded double cantilever beam (DCB) specimen is analytically expressed considering the deformation of the adhesive layer. The plastic zone length and strain during the crack propagation are obtained, and the effect of the traction–separation profile on the DCB test results is investigated. The fracture energy is given by the area under the traction–separation curve and is not affected by the curve profile. However, the crack length of the DCB specimen is strongly affected by the adhesive deformation, leading to a calculation error in the fracture energy. Therefore, several crack length correction methods have been proposed. An analytical approach to describe the plastic zone at the crack front would help better understand DCB tests for adhesives. In this study, an analytical solution for a DCB test is discussed assuming that the adhesive layer undergoes an elastic–plastic deformation. The elastic zone of the specimen is replaced with a beam on an elastic foundation and the plastic zone with a beam having a uniformly distributed load. Influence of the plastic zone at the crack front in the DCB tests is analytically described by assuming an elastic–perfectly plastic material. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Sarcopenia and osteoporosis are both serious health problems in postmenopausal women. The Asia Working Group for Sarcopenia recommends using the skeletal muscle index (SMI), which is height-adjusted appendicular skeletal muscle mass (ASMM). However, loss of height has been shown to be a common clinical finding in patients with osteoporosis. This study examined the prevalence of presarcopenia using height and arm span, which is a predictor of height, and investigated the diagnostic accuracy for presarcopenia. Methods: A total of 55 post-menopausal osteoporotic patients aged 62– 95 years underwent bioelectrical impedance analysis (BIA) for ASMM measurement and dual-energy X-ray absorptiometry (DXA) scan for bone mineral density (BMD). Anthropometric measurements, including height, weight, and arm span were taken, and body mass index (BMI), SMI, and arm span-adjusted SMI (Arm span SMI) were calculated. Presarcopenia was defined as SMI or Arm span SMI < 5.7 kg/m2 in this study. Results: The prevalence of presarcopenia was 27.3% and 38.2% evaluated by SMI and Arm span SMI, respectively. The prevalence of presarcopenia was higher when evaluated by Arm span SMI than by SMI. In the presarcopenia group diagnosed only by Arm span SMI (n=11), the arm span-height difference was significantly higher (p< 0.001) and the percentage of young adult mean (YAM) femoral neck-BMD was significantly lower (p=0.013) compared to the normal group diagnosed by both SMI and Arm span-SMI (n=29). Conclusion: These results indicated that Arm span SMI might be useful for the diagnosis of sarcopenia in patients with severe osteoporosis and kyphosis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Low-energy extracorporeal shock waves (LESW) have been studied as a new treatment for angina pectoris and several ischemic diseases because of its effect on angiogenesis and inhibition of fibrosis of the heart. The effect of LESW on fibrosis in liver cirrhosis has not been studied. The aim of this study was to verify the amelioration of liver fibrosis by LESW and elucidate its mechanisms in a rat model of drug-induced liver cirrhosis. Male Wistar rats aged 7 weeks were injected with carbon tetrachloride intraperitoneally twice a week for 12 weeks. Eight rats underwent LESW therapy (0.25 mJ/mm2, 4 Hz, 1000 shots) under general anesthesia (shock wave group). Seven rats only underwent general anesthesia (control group). Quantitative analysis showed that the area of fibrosis in the shock wave group was significantly reduced compared with the control group (11,899.9 vs. 23,525.3 pixels per field, p < 0.001). In the shock wave group, the mRNA expression of transforming growth factor (TGF)-β1 was significantly suppressed (0.40-fold, p = 0.018) and vascular endothelial growth factor-B was significantly increased (1.77-fold, p = 0.006) compared with the control group. Serum albumin was significantly higher in the shock wave group than in the control group (3.0 vs. 2.4 g/dl, p = 0.025). Aspartate aminotransferase/alanine aminotransferase ratio decreased by LESW compared with the control group (1.49 vs. 2.04, p = 0.013). These results suggest that LESW therapy ameliorates liver fibrosis by reducing the expression of TGF-β1 and increasing the expression of angiogenic factors, and improves hepatic function. [ABSTRACT FROM AUTHOR]

Background: Peroral endoscopic myotomy (POEM) is a novel, minimally invasive treatment for esophageal achalasia. We retrospectively examined and evaluated the results following POEM to verify the technique's efficacy and safety.Methods: We retrospectively analyzed data for patients who underwent POEM at eight Japanese facilities between September 2008 and October 2015. Pre- and postoperative assessments 3 months and 1 year after POEM included patient interviews, endoscopy, and manometry.Results: A total of 1346 patients underwent POEM during the study period. Achalasia was the straight type in 1105 patients (82%) and the sigmoid type in 241 patients (18%). The average patient age was 47.2 years (range 3-95 years); 617 patients (46%) were men and 729 (54%) were women. Previous treatment included balloon dilatation in 381 patients (28%) and Heller-Dor operation in 43 patients (3%). The average operation time was 99.6 min. The mean length of the myotomy in the esophageal body was 10.8 cm, and the myotomy extended into the stomach a mean of 2.8 cm. The response rate (Eckardt score ≤ 3) was 95.1% 3 months postoperatively and 94.7% 1 year postoperatively. We noted 50 adverse events (3.7%) of Clavien-Dindo classification grade ≤ IIIa, and all resolved with conservative treatment. There were no Clavien-Dindo classification grade ≥ IIIb adverse events. After POEM, erosive esophagitis according to the Los Angeles classification was absent in 37% of the patients, grade A in 33%, B in 24%, C in 6%, and D in 0.2%. Symptomatic gastroesophageal reflux disease after POEM was confirmed in 14.8% of the patients; both erosive esophagitis and symptomatic gastroesophageal reflux disease responded to treatment with a proton-pump inhibitor.Conclusion: Our results confirmed the safety and efficacy of POEM in a large patient series and support POEM as the first-line and standard treatment for esophageal achalasia. [ABSTRACT FROM AUTHOR]