Real-world evidence regarding enfortumab vedotin for unresectable or metastatic urothelial carcinoma is scarce, particularly in Japan. We investigated real-world data focusing on patient background, previous treatments, response, survival and adverse events in patients receiving enfortumab vedotin. A multicentre database was used to register 556 patients diagnosed with metastatic urothelial carcinoma from 2008 to 2023; 34 patients (6.1%) treated with enfortumab vedotin were included. Best radiographic objective responses were evaluated using the Response Evaluation Criteria in Solid Tumors (v1.1) during treatments. Overall survival and progression-free survival were estimated (Kaplan-Meier method). Toxicities were reported according to the Common Terminology Criteria for Adverse Events, version 5.0. The relative dose intensity, which could impact oncological outcomes, was calculated. The median number of enfortumab vedotin therapy cycles was 5. The best objective response to enfortumab vedotin was partial response, stable disease and progressive disease in 19 (56%), 5 (15%) and 10 (29%) patients, respectively. The median overall survival and progression-free survival after the first enfortumab vedotin dose were 16 and 9months, respectively. No significant relationship was observed between survival outcomes after enfortumab vedotin initiation and the enfortumab vedotin relative dose intensity. The median overall survival from first-line platinum-based chemotherapy initiation was 42months. Twenty-six (76%) patients experienced any grade of enfortumab vedotin-related toxicities; eight (24%) experienced Grades 3-4 toxicities, the most common being skin toxicity (any grade, 47%; Grades 3-4, 12%). Here, we report real-world evidence for enfortumab vedotin therapy in Japan. Tumour responses and safety profiles were comparable with those of clinical trials on this novel treatment.

ContextThe efficacy and tolerability of high-flow nasal cannula (HFNC) for relieving dyspnea in advanced cancer patients with limited prognosis requires elucidation. ObjectivesThe primary aim of this trial was to assess the efficacy and tolerability of HFNC regarding dyspnea including severe as well as moderate for longer durations in patients under palliative care. MethodsIn this prospective study, hospitalized patients with advanced cancer who had dyspnea at rest (numeric rating scale, NRS≥3) and hypoxemia were enrolled. They were treated with HFNC for five days in the respiratory unit. Primary endpoint was mean change of modified Borg scale at 24 hours. Key secondary endpoints consisted of mean changes in modified Borg scale during the study period and feasibility (Trial Identifier, UMIN000035738). ResultsBetween February 2019 and February 2022, 25 patients were enrolled and 21 were analyzed. Twenty patients used inspired oxygen and the mean fraction of inspired oxygen (FiO2) was 0.34 (range, 0.21–1.0). At baseline, mean NRS (dyspnea) was 5.9 (range, 3–10). Median survival time was 19 days (range, 3–657). The mean change of modified Borg scale was 1.4 (80% confidence interval [CI]: 0.8–1.9) at 24 hours, 12 patients (57%) showed 1.0 points improvement of modified Borg scale. Within two hours, 15 patients showed 1.0 points improvement of modified Borg scale and such early responders were likely to maintain dyspnea improvement for 24 hours. Nineteen patients could continue HFNC for 24 hours and 11 patients completed five days of HFNC. ConclusionTo our knowledge, this trial is the first prospective study to assess the five-day efficacy and tolerability of HFNC for dyspnea in patients under palliative care. Although this did not reach the prespecified endpoint, about half of the patients showed 1.0 point improvement, a minimally clinically important difference (MCID) in the chronic lung disease. HFNC can be a palliative treatment option in advanced cancer patients with dyspnea.

To examine whether serum β2-microglobulin (β2-MG) could improve the prediction performance for kidney failure with replacement therapy (KFRT) among patients with diabetic nephropathy (DN). Patients with biopsy-proven DN at Nara Medical University Hospital were included. The exposure of interest was log-transformed serum β2-MG levels measured at kidney biopsy. The outcome variable was KFRT. Multivariable Cox regression models and competing-risk regression models, with all-cause mortality as a competing event, were performed. Model fit by adding serum β2-MG levels was calculated using the Akaike information criterion (AIC). The net reclassification improvement (NRI) and integrated discrimination improvement (IDI) indexes were used to evaluate the improvement of predictive performance for 5-year cumulative incidence of KFRT by serum β2-MG levels. Among 408 patients, 99 developed KFRT during a median follow-up period of 6.7 years. A higher serum β2-MG level (1-unit increase in log-transformed serum β2-MG level) was associated with a higher incidence of KFRT, even after adjustments for previously known clinical and histological risk factors (hazard ratio [95% confidence interval {CI}]: 3.30 [1.57-6.94] and subdistribution hazard ratio [95% CI]: 3.07 [1.55-6.06]). The addition of log-transformed serum β2-MG level reduced AIC and improved the prediction of KFRT (NRI and IDI: 0.32 [0.09-0.54] and 0.03 [0.01-0.56], respectively). Among patients with biopsy-proven DN, serum β2-MG was an independent predictor of KFRT and improved prediction performance. In addition to serum creatinine, serum β2-MG should probably be measured for DN.

To clarify whether perioperative immunonutrition is effective in adult patients with or without malnutrition undergoing elective surgery for head and neck (HAN) or gastrointestinal (GI) cancers. It is important to avoid postoperative complications in patients with cancer as they can compromise clinical outcomes. There is no consensus on the efficacy of perioperative immunonutrition in patients with or without malnutrition undergoing HAN or GI cancer surgery. We searched MEDLINE (PubMed), MEDLINE (OVID), EMBASE, Cochrane Central Register of Controlled Trials, Web of Science Core Selection, and Emcare from 1981 to 2022 using search terms related to immunonutrition and HAN or GI cancer. We included randomized controlled trials. Intervention was defined as immunonutritional therapy including arginine, n-3 omega fatty acids, or glutamine during the perioperative period. The control was defined as standard nutritional therapy. The primary outcomes were total postoperative and infectious complications, defined as events with a Clavien-Dindo classification grade ≥ II that occurred within 30 days after surgery. Of the 4825 patients from 48 included studies, 19 had upper GI cancer, 9 had lower, and 8 had mixed cancer, whereas 12 had HAN cancers. Immunonutrition reduced the total postoperative complications (relative risk ratio: 0.78; 95% CI, 0.66-0.93; certainty of evidence: high) and infectious complications (relative risk ratio: 0.71; 95% CI, 0.61-0.82; certainty of evidence: high) compared with standard nutritional therapy. Nutritional intervention with perioperative immunonutrition in patients with HAN and GI cancers significantly reduced total postoperative complications and infectious complications.

The aim of this study was to evaluate the intra-abdominal status related to postoperative pancreatic fistula by combining postoperative fluid collection and drain amylase levels. We retrospectively reviewed the data of 203 patients who underwent distal pancreatectomy and classified their postoperative abdominal status into four groups based on postoperative fluid collection size and drain amylase levels. We also evaluated the incidence of clinically relevant postoperative pancreatic fistula in each group according to C-reactive protein values. The incidence of clinically relevant postoperative pancreatic fistula in the entire cohort (n = 203) was 28.1%. Multivariate analysis revealed that postoperative fluid collection, drain amylase levels, and C-reactive protein levels are considerable risk factors for clinically relevant postoperative pancreatic fistula. In the subgroup with large postoperative fluid collection and high drain amylase levels, 65.9% of patients developed clinically relevant postoperative pancreatic fistula. However, no significant difference was observed in C-reactive protein levels between patients with clinically relevant postoperative pancreatic fistula and those without it. In contrast, in the subgroup with a large postoperative fluid collection size or a high amylase level alone, a significant difference was observed in C-reactive protein values between the patients with clinically relevant postoperative pancreatic fistula and those without it. Postoperative fluid collection status and the C-reactive protein value provide a more precise assessment of intra=abdominal status related to postoperative pancreatic fistula after distal pancreatectomy. This detailed analysis may be a clinically reasonable approach to individual drain management.

Abstract Femoroacetabular impingement has increasingly been recognized as a cause of primary hip osteoarthritis; however, its epidemiological indications remain unclear. We aimed to clarify the epidemiological indications and factors associated with cam deformity in a large-scale population-based cohort in Japan. Overall, 1,480 participants (491 men, 989 women; mean age, 65.3 years) analyzed in the third survey of the Research on Osteoarthritis/Osteoporosis Against Disability study were included. The α angle and spinopelvic parameters (lumbar lordosis [LL], sacral slope [SS], pelvic tilt, and pelvic incidence) were radiographically measured. Cam deformity was defined as an angle ≥ 60°. Overall, 7.3% of patients had cam deformity on at least one side. Cam deformity prevalence tended to increase with age; a higher percentage of men was observed in the group with cam deformity than in that without it in the univariate analysis. LL and SS were significantly lower in the group with cam deformities. No relationship was observed between cam deformity and hip pain. Factors associated with α angle were examined via multiple regression analysis; α angle was significantly associated with age and male sex. Thus, α angle and cam deformity prevalence increase with age in Japanese individuals. Accordingly, cam deformity can be a developmental disease.

The coronavirus disease 2019 (COVID-19) pandemic impacted various parts of society, including Japanese children with allergies. This study investigated risk factors for pediatric allergic diseases associated with the state of emergency owing to the COVID-19 pandemic in Japan, including during school closures. Parents of pediatric patients (0-15 years) with allergies were enrolled and queried regarding the impact of school closure on pediatric allergies compared to that before the COVID-19 pandemic. A valid response was obtained from 2302 parents; 1740 of them had children with food allergies. Approximately 4% (62/1740) of the parents reported accidental food allergen ingestion was increased compared to that before the COVID-19 pandemic. Accidental ingestion during school closures was associated with increased contact with meals containing allergens meant for siblings or other members of the family at home. The exacerbation rate during the pandemic was highest for atopic dermatitis at 13% (127/976), followed by allergic rhinitis at 8% (58/697), and bronchial asthma at 4% (27/757). The main risk factors for worsening atopic dermatitis, allergic rhinitis, and bronchial asthma were contact dermatitis of the mask area (34/120 total comments); home allergens, such as mites, dogs, and cats (15/51 total comments); and seasonal changes (6/25 total comments), respectively. The main factors affecting allergic diseases were likely related to increased time at home, preventive measures against COVID-19, and refraining from doctor visits. Children with allergies were affected by changes in social conditions; however, some factors, such as preventing accidental ingestion and the management of allergens at home, were similar to those before the COVID-19 pandemic. Patients who had received instructions on allergen avoidance at home before the pandemic were able to manage their disease better even when their social conditions changed.

Introduction: Oral immunotherapy (OIT) imposes a burden on parents and their children with food allergies (FAs). We already developed a questionnaire for OIT-related Parental Burden (OIT-PB) scale. However, the previous questionnaire had some problems. This study modified OIT-PB and verified its reliability and validity. Methods: A 20-item draft covering the physical and mental burdens caused by OIT was prepared jointly with multiple allergists. The Food Allergy Quality of Life Questionnaire-Parental Burden (FAQLQ-PB) and Stress Response Scale-18 (SRS-18) were used to verify concurrent validity. A questionnaire survey was administered during treatment to parents of FA children who had started OIT for the first time. An additional OIT-PB survey was performed at one specific institution 1 week after the posttreatment survey. Results: The responses of 64 of the 76 recruited parents were analyzed. Of the 20 questions, 1 item was excluded owing to the floor effect, 1 was excluded because its commonality was less than 0.2, and 2 were excluded because their factor loading values were less than 0.4. Factor analysis was used to classify the OIT-PB into the following 4 subscales: “burden caused by adherence to treatment plan,” “anxiety about symptom-induced risk,” “burden due to patient’s eating behavior,” and “anxiety about treatment effect.” The Cronbach’s α for all 16 items of the OIT-PB was 0.893; Cronbach’s α for each subscale was 0.876, 0.898, 0.874, and 0.717. The re-test reliability coefficient was 0.864 (95% confidence interval [CI]: 0.720−0.937, p < 0.001). A significant positive correlation was found between the OIT-PB and FAQLQ-PB (R = 0.610 [95% CI: 0.422−0.747], p < 0.001) and the SRS-18 (R = 0.522 [95% CI: 0.306–0.687], p < 0.001). A significant negative correlation was found between the rate of increase in OIT food intake and the “anxiety about treatment effect” score (R = −0.355 [95% CI: −0.558–0.112], p < 0.001). Parents of children on the hen’s egg OIT treatment scored higher on the “burden due to patient’s eating behavior” subscale than did parents of children on the milk and wheat OIT treatment. Conclusion: The burden of OIT experienced by parents can be broadly classified into four categories. The modified OIT-PB was able to evaluate them individually and was shown to have reliability and validity. This scale is expected to be useful in the development of OIT that considers not only therapeutic effect but also the burden experienced by FA children and their parents.

S-1 plus cisplatin (SP) and capecitabine plus cisplatin (XP) are standard first-line regimens for advanced gastric cancer (AGC) worldwide. We conducted a meta-analysis using individual participant data (IPD) to investigate which is more suitable. IPD from three randomized trials were collected. In these trials, patients with AGC were randomly allocated to SP (S-1 80-120mg for 21days plus cisplatin 60mg/m2 (q5w)) or XP (capecitabine 2000mg/m2 for 14days plus cisplatin 80mg/m2 (q3w)). In 211 eligible patients, median overall survival (OS) for SP versus XP was 13.5 and 11.7months (hazard ratio [HR], 0.787; p = 0.114), progression-free survival (PFS) was 6.2 and 5.1months (HR, 0.767; P = 0.076), and TTF was 5.1 and 4.0months (HR, 0.611; P = 0.001). The most common grade ≥ 3 adverse events with SP or XP were neutropenia (18% vs. 29%) and anorexia (16% vs.18%). Subgroup analysis demonstrated significant interaction between treatment effect and performance status > 1 (HR, 0.685; P = 0.036), measurable lesion (HR, 0.709; P = 0.049), primary upper third tumor (HR, 0.539; P = 0.040), and differentiated type (HR, 0.549; interaction, 0.236; P = 0.019). For the differentiated type, OS was significantly longer in the SP group (13.2months) than in the XP group (11.1months) (HR, 0.549; P = 0.019). For the undifferentiated type, OS was similar in the SP group (14.2months) and in the XP group (12.4months) (HR, 0.868; P = 0.476). SP and XP were both effective and well tolerated. SP might be suitable for the pathological differentiated subtype of AGC. The HERBIS-2, HERBIS-4A, and XParTS II trials were registered with UMIN-CTR as UMIN000006105, UMIN000006755, and UMIN000006045, respectively.

Laparoscopic distal gastrectomy for gastric cancer has become a common procedure in many institutions. As manual palpation is impossible, various methods have been developed to identify the location of the tumor and determine the proximal resection line. Intraoperative endoscopy requires manpower and is time-consuming. The authors take an intraoperative X-ray. Here, we demonstrate our methods and outcomes. We preoperatively applied metal clips just proximal to the tumor through esophagogastroduodenoscopy. During surgery, we applied metal vessel clips to the greater and lesser curvatures of the planned resection line of the stomach and took an intraoperative X-ray to examine the distance between the planned resection line and the tumor. If the distance was appropriate, the stomach was resected on the planned line, and if the distance was judged to be insufficient, the stomach was resected on the more proximal line, as appropriate. An intraoperative frozen section of the proximal resection margin was examined, as appropriate. We performed this method for 71 patients. Tumors were successfully resected together with preoperative endoscopic clips in all patients. In five patients, intraoperative frozen section of the proximal resection margins was positive; however, additional resection confirmed negative margins. One patient underwent total gastrectomy, and the remaining 70 patients underwent distal gastrectomy. An intraoperative X-ray seems to be a simple and useful method for identifying the location of the tumor and determining the proximal resection line.