Objective: The package inserts are official clinical decision-making documents that provide pharmacological treatment information. However, it has been noted that package inserts on perinatal drug usage differ greatly from expert opinions. This study identified Japanese package insert drugs that are contraindicated for pregnant women and compared them to foreign risk categories.Methods: The survey included 19,022 drugs on the drug pricing list as of April 2022, with package inserts available on the Pharmaceuticals and Medical Devices Agency website. We retrieved the package inserts with the word “pregnant” in the “Contraindications” section and reviewed the descriptions to exclude those that satisfied the exclusion criteria. We also checked the foreign risk categories of contraindicated ingredients for pregnant women. This study used the Australian Therapeutic Goods Administration’s categorization for prescribing medicines in pregnancy (the TGA classification).Results: Of the 19,022 medicines studied, 4,111 (21.6%) were contraindicated for pregnant women. Conversely, 19 (5.1%) ingredients categorized under the relatively safe TGA classifications A, B1, and B2 were also contraindicated for pregnant Japanese women.Conclusion: This study revealed that Japanese package inserts contraindicate over 20% of drugs for pregnant women. On the other hand, some forbidden ingredients did not match the foreign risk categories. Therefore, healthcare professionals should be aware of the limitations of Japanese package inserts concerning pregnant women and make careful decisions based on both package inserts and additional drug information.

Background/Aims: Asymptomatic esophageal eosinophilia (aEE) is considered to be a potential precursor of eosinophilic esophagitis (EoE). However, there are few clinical parameters that can be used to evaluate the disease. Therefore, we aimed to clarify the factors involved in the symptoms of EoE by examining the clinicopathological differences between aEE and EoE. Methods: We reviewed 41 patients with esophageal eosinophilia who underwent endoscopic ultrasonography and high-resolution manometry. They were divided into the aEE group (n=16) and the EoE group (n=25) using the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease score. The patients’ clinicopathological findings were collected and examined. Results: The median Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease score was 3.0 in the aEE group and 10.0 in the EoE group. There was no significant difference in patient characteristics, endoscopic findings and pathological findings. The cutoff value for wall thickening was 3.13 mm for the total esophageal wall thickness and 2.30 mm for the thickness from the surface to the muscular layer (total esophageal wall thickness: 84.0% sensitivity, 75.0% specificity; thickness from the surface to the muscular layer: 84.0% sensitivity, 68.7% specificity).The high-resolution manometry study was abnormal in seven patients (43.8%) in the aEE group and in 12 (48.0%) in the EoE group. The contractile front velocity was slower in the EoE group (p=0.026). Conclusions The esophageal wall thickening in the lower portion of the esophagus is an important clinical factors related to the symptoms in patients with EoE.

Background/Aims: Asymptomatic esophageal eosinophilia (aEE), characterized by eosinophil infiltration in the esophagus without clinical symptoms, has been reported as a precursor of eosinophilic esophagitis (EoE). Nevertheless, no report exists on the long-term clinical course of the disease. Therefore, this study aimed to investigate the long-term clinical course of aEE over 5 years, including the symptomatic conversion rate and the effect of treatments. Methods: We reviewed 28 patients with aEE who had been followed up for over 5 years with endoscopic monitoring. The basal characteristics of patients were compared with those of 58 patients diagnosed with EoE during the same period. Patients’ clinicopathological findings were collected and examined. Results: No significant differences in basal characteristics and histopathological findings were observed between the patients with aEE and those with EoE. The median follow-up duration was 64 months. Among the 28 patients with aEE, seven were treated with proton pump inhibitor or potassium-competitive acid blocker and the remaining 21 opted for follow-up with no medication.Among the treated patients, six (85.7%) exhibited endoscopic and pathologic improvements.Among the cases followed up without medication, the findings worsened in two (9.5%), improved spontaneously in seven (33.3%), and were unchanged in 12 (57.1%), and three (14.3%) developed symptoms at a mean time of 40 months. Symptoms developed in cases where endoscopic and pathologic findings remained unchanged or worsened during follow-up. Conclusions Some patients with aEE had improved findings without treatment, whereas others developed symptoms, emphasizing the importance of long-term monitoring and individualized treatment decisions.

Tohoku Medical and Pharmaceutical University Hospital uses an information form created by doctors and pharmacists to provide postoperative information to patients who undergo nephrectomy at the Department of Urology. The form recommends that patients' physicians change prescriptions and adjust medication doses considering post-nephrectomy deterioration of renal function in patients with a single remaining kidney. Of the 7 patients who used this information form, prescription changes were made in 4 patients. An information form jointly created by a physician and pharmacist may affect prescription changes.

Background/Aims: Thiopurines are key drugs for inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD). Recently, NUDT15 polymorphism (R139C, c.415C > T) has been shown to be associated with thiopurineinduced adverse events in Asian populations. In patients with the C/T genotype, low-dose thiopurine treatment is recommended, but its long-term efficacy and tolerability remain unclear. This study aimed to uncover the long-term efficacy and appropriate dosage of thiopurine for IBD patients with the C/T genotype. Methods: A total of 210 patients with IBD (103 UC and 107 CD) determined to have NUDT15 R139C variants were enrolled. Clinical data were retrospectively reviewed from medical records. Results: Of 46 patients (21.9%) with the C/T genotype, 30 patients (65.2%) were treated with thiopurines. Three of whom (10.0%) discontinued thiopurine treatment due to adverse events and 27 of whom continued. The median maintenance dosage of 6-mercaptopurine was 0.25 mg/kg/day (range, 0.19–0.36 mg/kg/day), and 6-thioguanine nucleotides level was 230 (104–298) pmol/8 × 108 red blood cells. Cumulative thiopurine continuation rates for 120 months for patients with the C/C and C/T genotypes were not significantly different (P= 0.895). Cumulative non-relapse rates in the patients with UC treated with thiopurine monotherapy and surgery-free rates in CD patients treated with combination therapy (thiopurines and anti-tumor necrosis factor-α agents) for maintenance remission were not significantly different at 60 months (C/C vs. C/T, P= 0.339 and P= 0.422, respectively). Conclusions Low-dose thiopurine treatment is an effective and acceptable treatment for patients with C/T genotype.

Background/Aims: Esophageal motility disorders (EMDs) contribute to the pathophysiology of gastroesophageal reflux disease. However, the causes of EMDs and their impact on gastroesophageal reflux disease-associated symptoms remain unknown. This study aims to elucidate clinical features associated with various types of EMDs in patients with heartburn symptoms. Methods: Of the 511 patients who underwent high-resolution manometry, 394 who were evaluated for heartburn symptoms were examined. Patients subjected to high-resolution manometry were classified into 4 groups: outflow obstruction group, hypermotility group, hypomotility group, and normal motility group. Symptoms were evaluated using 3 questionnaires. Patient characteristics and symptoms for each EMD type were compared with those of the normal motility group. Results: Of the 394 patients, 193 (48.9%) were diagnosed with EMDs, including 71 with outflow obstruction, 15 with hypermotility, and 107 with hypomotility. The mean dysphagia score was significantly higher in each of the 3 EMD groups compared with those with normal motility. The mean acid reflux and dyspepsia scores were significantly lower in the outflow obstruction group (P < 0.05). The mean body mass index and median Brinkman index were significantly higher in the hypermotility group (P = 0.001 and P = 0.018, respectively), whereas the mean diarrhea and constipation scores were significantly lower in the hypomotility group (P < 0.05). Conclusions The results of our study indicate that different EMDs have distinct characteristics. Cigarette smoking and high body mass index were associated with esophageal hypermotility. Assessment of the dysphagia symptom scores may help identify patients with EMDs.

Background/Aims: Esophageal motility disorders (EMDs) contribute to the pathophysiology of gastroesophageal reflux disease. However, the causes of EMDs and their impact on gastroesophageal reflux disease-associated symptoms remain unknown. This study aims to elucidate clinical features associated with various types of EMDs in patients with heartburn symptoms. Methods: Of the 511 patients who underwent high-resolution manometry, 394 who were evaluated for heartburn symptoms were examined. Patients subjected to high-resolution manometry were classified into 4 groups: outflow obstruction group, hypermotility group, hypomotility group, and normal motility group. Symptoms were evaluated using 3 questionnaires. Patient characteristics and symptoms for each EMD type were compared with those of the normal motility group. Results: Of the 394 patients, 193 (48.9%) were diagnosed with EMDs, including 71 with outflow obstruction, 15 with hypermotility, and 107 with hypomotility. The mean dysphagia score was significantly higher in each of the 3 EMD groups compared with those with normal motility. The mean acid reflux and dyspepsia scores were significantly lower in the outflow obstruction group (P < 0.05). The mean body mass index and median Brinkman index were significantly higher in the hypermotility group (P = 0.001 and P = 0.018, respectively), whereas the mean diarrhea and constipation scores were significantly lower in the hypomotility group (P < 0.05). Conclusions The results of our study indicate that different EMDs have distinct characteristics. Cigarette smoking and high body mass index were associated with esophageal hypermotility. Assessment of the dysphagia symptom scores may help identify patients with EMDs.

Objectives: This review aims to introduce preoperative scoring systems to predict lymph node metastasis (LNM) and ongoing clinical trials to investigate the therapeutic role of lymphadenectomy for endometrial cancer. Methods: We summarized previous reports on the preoperative prediction models for LNM and evaluated their validity to omit lymphadenectomy in our recent cohorts. Next, we compared characteristics of two ongoing lymphadenectomy trials (JCOG1412, ECLAT) to examine the survival benefit of lymphadenectomy in endometrial cancer, and described the details of JCOG1412. Results: Lymphadenectomy has been omitted for 64 endometrial cancer patients who met lowrisk criteria to omit lymphadenectomy using our scoring system (LNM score) and no lymphatic failure has been observed. Other two models also produced comparable results. Two randomized phase III trials to evaluate survival benefit of lymphadenectomy are ongoing for endometrial cancer. JCOG1412 compares pelvic lymphadenectomy alone with pelvic and para-aortic lymphadenectomy to evaluate the therapeutic role of para-aortic lymphadenectomy for patients at risk of LNM. For quality assurance of lymphadenectomy, we defined several regulations, including lower limit of the number of resected nodes, and submission of photos of dissected area to evaluate thoroughness of lymphadenectomy in the protocol. The latest monitoring report showed that the quality of lymphadenectomy has been well-controlled in JCOG1412. Conclusion Our strategy seems reasonable to omit lymphadenectomy and could be generalized in clinical practice. JCOG1412 is a high-quality lymphadenectomy trial in terms of the quality of surgical procedures, which would draw the bona-fide conclusions regarding the therapeutic role of lymphadenectomy for endometrial cancer.

Objective：To investigate the physical functions of peripheral arterial disease (PAD) patients undergoing endovascular treatment (EVT), and their association with physical activity before EVT.Methods：One hundred and one PAD patients underwent EVT. Physical functions were specified as grip strength, walking speed, and the weight ratio of knee extension isometric muscle strength (KEIS). We divided the patients into 3 groups, based on the amount of physical activity per week：(a) low activity (0 kcal/week：n＝52), (b) moderate activity (0 kcal to less than 500 kcal/week：n＝22), and (c) high activity (more than 500 kcal/week：n＝27). Physical activity data were collected using an international standardized physical activity questionnaire. A multivariate regression analysis (cumulative logit model) was used to evaluate the association between physical activity (low activity, moderate activity, high activity) and KEIS＜0.4 kgf/kg.Results：The averages of the physical functions were：grip strength (kg；Men 28.1, Women 16.6), walking speed (m/s；Men 1.10, Women 0.96), KEIS (kgf/kg；Men 0.42, Women 0.28). The prevalence of KEIS＜0.4 kgf/kg was 56.4％ (n＝57). KEIS＜0.4 kgf/kg was not significantly different between low and moderate activity groups (Odds：0.99, p＝0.98). However, KEIS＜0.4 kgf/kg was significantly different between low and high activity groups (Odds：5.02, p＝0.007).Conclusion：Physical functions were lower in PAD patients undergoing EVT than in healthy adults of the same age, and KEIS was related to physical activity before EVT.

Objective：To investigate the physical functions of peripheral arterial disease (PAD）patients undergoing endovascular treatment (EVT), and their association with physical activity before EVT.Methods：One hundred and one PAD patients underwent EVT. Physical functions were specified as grip strength, walking speed, and the weight ratio of knee extension isometric muscle strength (KEIS). We divided the patients into 3 groups, based on the amount of physical activity per week：(a) low activity (0 kcal/week：n＝52), (b）moderate activity (0 kcal to less than 500 kcal/week：n＝22), and (c) high activity (more than 500 kcal/week：n＝27). Physical activity data were collected using an international standardized physical activity questionnaire. A multivariate regression analysis (cumulative logit model) was used to evaluate the association between physical activity (low activity, moderate activity, high activity) and KEIS＜0.4 kgf/kg.Results：The averages of the physical functions were：grip strength (kg；Men 28.1, Women 16.6), walking speed (m/s；Men 1.10, Women 0.96), KEIS (kgf/kg；Men 0.42, Women 0.28). The prevalence of KEIS＜0.4 kgf/kg was 56.4％ (n＝57). KEIS＜0.4 kgf/kg was not significantly different between low and moderate activity groups (Odds：0.99, p＝0.98). However, KEIS＜0.4 kgf/kg was significantly different between low and high activity groups (Odds：5.02, p＝0.007).Conclusion：Physical functions were lower in PAD patients undergoing EVT than in healthy adults of the same age, and KEIS was related to physical activity before EVT.