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Background: Interstitial lung disease/pneumonitis (ILD/pneumonitis) has been identified as a drug-related adverse event of special interest of trastuzumab deruxtecan (T-DXd), but there were a few reports of T-DXd-related ILD/pneumonitis in clinical practice. Methods: Between May 25, 2020 (the launch of T-DXd in Japan) and February 24, 2022, there were 287 physician-reported potential ILD/pneumonitis cases from the Japanese post-marketing all-case surveillance. By February 27, 2022, an independent adjudication committee assessed 138 cases and adjudicated 130 cases as T-DXd-related ILD/pneumonitis. The clinical features and imaging characteristics of these cases were evaluated. Results: The majority of adjudicated T-DXd-related ILD/pneumonitis cases were grade 1 or 2 (100/130, 76.9%). The most common radiological pattern types observed were organizing pneumonia patterns (63.1%), hypersensitivity pneumonitis patterns (16.9%), and diffuse alveolar damage (DAD) patterns (14.6%). Eleven cases (8.5%) from 130 resulted in death; the majority of these (8/11, 72.7%) had DAD patterns. The overall proportion of recovery (including the outcomes of recovered, recovered with sequelae, and recovering) was 76.9%, and the median time to recovery was 83.5 days (interquartile range: 42.25–143.75 days). Most cases (59/71, 83.1%) that were treated with corticosteroids were considered responsive to treatment. Conclusions: This is the first report to evaluate T-DXd-related ILD/pneumonitis cases in clinical practice. Our findings are consistent with previous reports and suggest that patients with DAD patterns have poor outcomes. Evaluation of a larger real-world dataset may further identify predictors of clinical outcome. [ABSTRACT FROM AUTHOR]

With recent developments in ICT, the interest in using large amounts of accumulated data for traffic policy planning has increased significantly. In recent years, data polishing has been proposed as a new method of big data analysis. Data polishing is a graphical clustering method, which can be used to extract patterns that are similar or related to each other by identifying the cluster structures present in the data. The purpose of this study is to identify the travel patterns of railway passengers by applying data polishing to smart card data collected in the Kagawa Prefecture, Japan. To this end, we consider 9,008,709 data points collected over a period of 15 months, ranging from December 1st, 2013 to February 28th, 2015. This dataset includes various types of information, including trip histories and types of passengers. This study implements data polishing to cluster 4,667,520 combinations of information regarding individual rides in terms of the day of the week, the time of the day, passenger types, and origin and destination stations. Via the analysis, 127 characteristic travel patterns are identified in aggregate. [ABSTRACT FROM AUTHOR]

Coronary catheterization by a distal radial approach at the site of the anatomical snuffbox has recently been reported to be both safe and useful. No data are available on the diameter of the distal radial artery (DRA) in Japan, and it is unclear whether the DRA is large enough to withstand the insertion of a conventional sheath by a traditional radial approach. We enrolled 142 patients who underwent coronary catheterization and evaluated the vessel diameter of the DRA using ultrasound. The vessel diameter of the DRA in the anatomical snuffbox (2.6 ± 0.5 mm) was significantly smaller than that of the proximal radial artery (PRA) at the conventional puncture site (3.1 ± 0.4 mm). The difference in vessel diameter between the DRA and PRA was 0.5 ± 0.4 mm, and the DRA/PRA ratio was 0.8 ± 0.1. Although the vessel diameter of the DRA was positively correlated with that of the PRA (r = 0.66, p < 0.0001), in some cases the DRA was extremely small compared to the PRA. When the vessel diameter of the DRA is smaller than the outer diameter of the sheath scheduled for use, we should puncture the PRA at the outset. We could perform coronary catheterization by a distal radial approach without major bleeding or adverse events, and there was no radial artery occlusion at the site of the anatomical snuffbox or the forearm. For coronary catheterization by a distal radial approach, we should evaluate whether there is sufficient vessel diameter using ultrasound before the procedure. In addition, this approach can be an effective option from the viewpoint of radial artery preservation. [ABSTRACT FROM AUTHOR]

Purpose: To define the effects of body mass index (BMI) on operative outcomes for both gastroenterological and cardiovascular surgery, using the National Clinical Database (NCD) of the Japanese nationwide web-based database. Methods: The subjects of this study were 288,418 patients who underwent typical surgical procedures between January 2011 and December 2012. There were eight gastroenterological procedures, including esophagectomy, distal gastrectomy, total gastrectomy, right hemicolectomy, low anterior resection, hepatectomy of >1 segment excluding the lateral segment, pancreaticoduodenectomy, and surgery for acute diffuse peritonitis ( n = 232,199); and five cardiovascular procedures, including aortic valve replacement, total arch replacement (TAR), descending thoracic aorta replacement (descending TAR), and on- or off-pump coronary artery bypass grafting ( n = 56,219). The relationships of BMI with operation time and operative mortality for each procedure were investigated, using the NCD. Results: Operation times were longer for patients with a higher BMI. When a BMI cut-off of 30 was used, the operation time for obese patients was significantly longer than that for non-obese patients, for all procedures except esophagectomy ( P < 0.01). The mortality rate based on BMI revealed a U-shaped distribution, with both underweight and obese patients having high mortality rates for almost all procedures. Conclusions: This Japanese nationwide study provides solid evidence to reinforce that both obesity and excessively low weight are factors that impact operative outcomes significantly. [ABSTRACT FROM AUTHOR]

A questionnaire-based survey on chemotherapy-induced anemia (CIA) in cancer patients was conducted between September and November 2010. The number of patients treated with chemotherapy, rate of blood transfusion, volume of blood transfused, severity of anemia, and factors affecting blood transfusion were analyzed according to the type of cancer, in an attempt to clarify the current status of CIA in Japan. During the survey period, among the eight types of cancer analyzed (breast, lung, stomach, colorectal, liver, gynecologic cancer, urologic cancer, and malignant lymphoma), chemotherapy was given to 5.4-13.6 % (mean 9.2 %) of patients, among whom 1.6-24.0 % (mean 7.5 %) required blood transfusion. The number of units of red blood cells transfused was 3.9-7.3 units (mean 5.9 units) per patient. According to a nationwide patient survey conducted by the Ministry of Health, Labour and Welfare, it is estimated that approximately 146,000 units of red blood cells, which account for 2.2 % of the annual total supply of red blood cell products, are transfused to cancer patients with CIA yearly. In addition, it is estimated that annually approximately 172,000 cancer patients with CIA, accounting for 40 % of patients receiving chemotherapy, have hemoglobin (Hb) levels below 10 g/dL. Possible factors affecting blood transfusion include a history of chemotherapy and radiotherapy, as well as the use of platinum agents. In patients who received red blood cell transfusions, the average Hb level prior to chemotherapy was 9.5 g/dL, and the average lowest Hb level after starting chemotherapy was 6.9 g/dL. By contrast, in patients who did not receive transfusion, these values were 11.6 and 10.4 g/dL, respectively. Furthermore, in all cancer types, almost no red blood cell transfusion was performed in patients with an Hb level of 8.0 g/dL or higher, but also many patients with an Hb level of 6.9 g/dL or lower did not receive red blood cell transfusions. There was no significant difference in the ratio of adverse events following blood transfusion in this survey compared with that in the nationwide survey. The present results demonstrate the strict restriction of red blood cell transfusion to cancer patients with CIA. Therefore, there is a need to consider the use of alternative therapies to allogeneic blood transfusion, such as erythropoiesis-stimulating agents, to increase Hb levels, and consequently improve the quality of life in cancer patients with CIA. [ABSTRACT FROM AUTHOR]

Background: Traditional Japanese medicine, known as Kampo medicine, consists of mixtures of several medicinal herbs widely used to treat upper gastrointestinal disorders in Japan. Rikkunshito, one of these medicines, has not been evaluated with respect to its influence on gastrointestinal motor activity. We investigated the effect of rikkunshito on upper gastrointestinal motility and plasma ghrelin concentrations in conscious dogs. Methods: Contractile response to intragastric administration of rikkunshito was studied via surgically implanted force transducers. A powdered extract of rikkunshito (1.3, 2.7, and 4.0 g) dissolved in water was administered into the stomachs of normal and vagotomized dogs before feeding and gastric emptying was evaluated. Several inhibitors of gastrointestinal motility (atropine, hexamethonium, and ondansetron) were injected intravenously before intragastric administration of rikkunshito. Plasma acylated ghrelin levels after intragastric administration of rikkunshito were measured. Results: In a fasting state, intragastric administration of rikkunshito induced phasic contractions in the duodenum and jejunum in normal dogs. Rikkunshito-induced contractions were inhibited by atropine, hexamethonium and ondansetron. In vagotomized dogs, rikkunshito induced phasic contractions, similar to normal dogs. Gastric emptying was accelerated by intragastric administration of rikkunshito in a dose-dependent manner. The plasma acylated ghrelin level 150 min after intragastric administration of 4.0 g of rikkunshito was significantly higher than the control value. Conclusions: Intragastric administration of rikkunshito stimulates gastrointestinal contractions in the interdigestive state through cholinergic neurons and 5-HT type 3 receptors. Moreover, rikkunshito increases plasma acylated ghrelin levels. Rikkunshito may alleviate gastrointestinal disorders through its prokinetic effects. [ABSTRACT FROM AUTHOR]

Background:A combination of S-1 and cisplatin has been shown to be effective with acceptable safety for the first-line treatment of far-advanced gastric cancer in Japan. This is the first randomised phase II trial to compare S-1+paclitaxel with S-1+cisplatin in this setting.Methods:Patients with unresectable and/or recurrent advanced gastric cancer were randomly assigned to receive one of the two regimens: S-1 (40 mg m−2 twice daily) on days 1-14 plus paclitaxel (60 mg m−2) on days 1, 8, and 15 of a 4-week cycle (S-1+paclitaxel) or S-1 (40 mg m−2 twice daily) on days 1-21 plus cisplatin (60 mg m−2) on day 8 of a 5-week cycle (S-1+cisplatin). The primary end point was the response rate (RR). Secondary end points included progression-free survival (PFS), overall survival (OS), and safety.Results:A total of 83 patients were eligible for safety and efficacy analyses. In the S-1+paclitaxel and S-1+cisplatin groups, RRs (52.3% vs 48.7%; P=0.74) and median PFS (9 vs 6 months; P=0.50) were similar. The median OS was similar in the S-1+paclitaxel and S-1+cisplatin groups (16 vs 17 months; P=0.84). The incidence of grade 3 or higher haematological toxicity was 19.0% with S-1+paclitaxel and 19.5% with S-1+cisplatin. The incidence of grade 3 or higher non-haematological toxicity was 14.2% with S-1+paclitaxel and 17.1% with S-1+cisplatin.Conclusion:S-1+paclitaxel was suggested to be a feasible and effective non-platinum-based regimen for chemotherapy in patients with advanced gastric cancer. Our results should be confirmed in multicenter, phase III-controlled clinical trials. [ABSTRACT FROM AUTHOR]

Family and twin studies have indicated that genetic factors have an important role in panic disorder (PD), whereas its pathogenesis has remained elusive. We conducted a genome-wide copy number variation (CNV) association study to elucidate the involvement of structural variants in the etiology of PD. The participants were 2055 genetically unrelated Japanese people (535 PD cases and 1520 controls). CNVs were detected using Genome-Wide Human SNP array 6.0, determined by Birdsuite and confirmed by PennCNV. They were classified as rare CNVs (found in <1% of the total sample) or common CNVs (found in 5%). PLINK was used to perform global burden analysis for rare CNVs and association analysis for common CNVs. The sample yielded 2039 rare CNVs and 79 common CNVs. Significant increases in the rare CNV burden in PD cases were not found. Common duplications in 16p11.2 showed Bonferroni-corrected P-values <0.05. Individuals with PD did not exhibit an increased genome-wide rare CNV burden. Common duplications were associated with PD and found in the pericentromeric region of 16p11.2, which had been reported to be rich in low copy repeats and to harbor developmental disorders, neuropsychiatric disorders and dysmorphic features. [ABSTRACT FROM AUTHOR]

To identify susceptibility genes for endometriosis in Japanese women, genome-wide association (GWA) analysis was performed using two case-control cohorts genotyped with the Affymetrix Mapping 500K Array or Genome-Wide Human SNP Array 6.0. In each of the two array cohorts, stringent quality control (QC) filters were applied to newly obtained genotype data, together with previously analyzed data from the Japanese Integrated Database Project. After QC-based filtering of samples and single nucleotide polymorphisms (SNPs) in each cohort, 282 838 SNPs in both genotyping platforms were tested for association with endometriosis using a meta-analysis of the two GWA studies with 696 patients with endometriosis and 825 controls. The meta-analysis revealed that a common susceptibility locus conferring a large effect on the disease risk was unlikely. On the other hand, an excess of SNPs with P-values <10−4 (36 vs 28 SNPs expected by chance) was observed in the meta-analysis. Of note, four of the top five SNPs with P-values <10−5 were located in and around IL1A (interleukin 1α), which might be a functional candidate gene for endometriosis. Further studies with larger case-control cohorts will be necessary to elucidate the genetic risk factors. [ABSTRACT FROM AUTHOR]

Endoluminal gastroplication (ELGP) was the first endoscopic therapy for gastroesophageal reflux disease (GERD). Data on the long-term outcomes, including the plication status and data from Asian populations, are limited. The aim of this study was to evaluate the short-term and long-term effectiveness and safety of ELGP for GERD in the Japanese population. This was an open-label, prospective, multicenter trial of ELGP. Forty-eight patients with GERD were enrolled. The procedure involved placing circumferential plications 1–2 cm below the GE junction using the EndoCinch system. Outcome measurements were improvement of heartburn, medication use, endoscopic Los Angeles grade, durability of plications, 24-h esophageal acid exposure, esophageal manometry, and frequency of adverse events. During the 24-month follow-up, the rate of complete resolution of heartburn ranged from 54 to 66%, the rate of discontinuation or reduction of PPI/H2RA use ranged from 65 to 76%, and the rate of endoscopic classification to grade O ranged from 66 to 81%. The status with more than one plication remaining was associated with higher rates of improvement of heartburn, PPI/H2RA use, and endoscopic findings as compared with those associated with the loss of all plications. A modest decrease of the esophageal acid exposure level, but no change of the manometric parameters, was observed after ELGP. No serious adverse events were observed. In this 24-month follow-up study conducted in Japanese subjects, ELGP was found to be effective in about 60% of patients with GERD, and the procedure was safe. [ABSTRACT FROM AUTHOR]

Abstract  We report a case of a granular cell tumor (GCT) covered by squamous cell carcinoma (SCC) in the esophagus. A 69-year-old Japanese man was admitted to our hospital for treatment of superficial esophageal cancer detected by upper gastrointestinal endoscopy. Endoscopic examination revealed a shallow ulcer in the esophagus, 28–32 cm from the incisor teeth. The pathological findings of a biopsy of the lesion were moderately differentiated SCC. Thus, we performed partial esophagectomy with two-field (thoraco-abdominal) lymph node dissection. Microscopic examination of the surgical specimen revealed intraepithelial SCC with minimal invasion, and a GCT, 3 × 1 mm in size, in the submucosa just beneath the SCC. Cytoplasmic granules in the GCT were positive for periodic acid-Schiff. Immunohistochemically, the GCT was strongly positive for S-100 protein. To our knowledge, this is the first published report of a GCT covered by SCC in the esophagus. [ABSTRACT FROM AUTHOR]

Rhabdomyosarcomas of the perianal and perineal regions are uncommon. This study was performed to clarify the clinical characteristics and guidelines of surgical treatment of patients with perianal and perineal rhabdomyosarcomas younger than 20 years of age. Twenty-nine patients, 26 patients identified in the Japanese literature and three of our own, were analyzed and the results were compared with the data reported from the Intergroup Rhabdomyosarcoma Study Group (IRSG). Female predominance and a twin-peak age distribution in infancy and adolescence were characteristic findings of the Japanese patients that were not observed in the IRSG studies. The demographic differences between the two groups were attributed to the differences in demographics of patients younger than 10 years of age. Of the 29 patients, 17 were categorized into clinical groups III/IV and 21 patients into stages 3/4. Alveolar histology was diagnosed in 18 patients. In patients more than 10 years of age, the female predominance was more prominent and the incidences of advanced clinical groups/stages and alveolar histology were significantly higher than those in patients younger than 10 years of age. Inguinal lymph nodes were always involved in patients with lymph node metastases and three patients developed metastases to the breast. Information regarding the survival time was available for 18 patients and the 5-year overall survival was 20%. Two patients with a group I/stage 2 tumor and one with a group II/stage 3 tumor survived for more than 2 years with no evidence of the disease. In these patients, the tumors were excised by primary surgery or primary reexcision and they were not accompanied by lymph node metastasis. Based on these data, complete tumor resection prior to chemotherapy should be pursued and the inguinal lymph nodes should be at least sampled because nodal involvement is closely associated with the patient's prognosis. [ABSTRACT FROM AUTHOR]