Tumor necrosis factor receptor-associated factor 3 (TRAF3) is an anti-inflammatory molecule that negatively regulates the non-canonical nuclear factor-κB pathway. Although TRAF3 haploinsufficiency (TRAF3 HI) can influence innate and adaptive immune cells, its effect on inflammatory bowel disease (IBD) development remains unclear. Here, we report the first case of severe early-onset IBD with a novel TRAF3 variant leading to HI, successfully treated with ustekinumab. A 6-year-old girl with a recurrent parotitis, otitis media, tonsilitis, and atopic dermatitis developed IBD involving the stomach, small intestine, and colon. At diagnosis, the immunoglobulin (Ig)G and IgA levels were relatively high, and lymphocyte subsets showed increased counts of plasmablasts, class-switch recombination B cells, and circulating T-follicular helper cells. Treatment with azathioprine and infliximab failed to maintain remission marked by several relapses accompanied by erythema nodosum and arthritis; however, ustekinumab, an anti-interleukin (IL)-12/23p40 antibody, led to long-term clinical remission, normalizing the Ig level and reducing abnormal lymphocyte counts. Whole-exome sequencing revealed a novel heterozygous mutation in TRAF3 [p.(Pro487Leufs*8)], resulting in TRAF3 under-expression. Our case may highlight the contribution of TRAF3 HI to the development of IBD and provide insights into IBD pathophysiology, suggesting the involvement of the IL-12/23-T-follicular helper cell pathway affected by genetic mutations.

Even within a hospital, the prognosis after a cardiac arrest is extremely poor if intervention starts only after the event; thus, early recognition and intervention is crucial to reduce inhospital cardiac arrests. This paper aims to assess the results of in-clinic surveys conducted for the implementation of the Rapid Response System (RRS) at our hospital and changes in awareness after awareness initiatives. Excluding the neonatal intensive care unit, all wards were targeted for implementation, with the creation of criteria for requesting the RRS and hospital-wide awareness initiatives. Four items were defined for the request criteria—namely, (1) respiration, (2) circulation, (3) state of consciousness, and (4) others (any concerns)—with a request being warranted if any one of these criteria was met. A pre-awareness survey revealed that respiratory rates were recorded only 6.9% of the time on average, indicating inadequate observation of respiratory rates across all wards. In response to this issue, we announced that respiratory status should be observed at least once a day, which resulted in the recording rate improving to 68.2% after 2 months. Survey results before and after the awareness initiatives among doctors and nurses showed a significant increase in RRS awareness. The percentage of nurses who answered “well aware” or “somewhat aware” increased from 34.8% to 77.6%, and from 63.4% to 88.0% among doctors. However, while the introduction of the RRS was relatively well-received by nurses struggling with on-site responses, some doctors questioned the necessity of the RRS. Upon implementation, it is important to make it known that it is a hospital-wide effort. Simplifying and thoroughly utilizing the request criteria can lead to early recognition of abnormalities. Since it is not easy to gain doctors’ understanding, it is necessary to listen to the needs and requests of each department and patiently continue awareness activities before implementation

Objective: This multi-center retrospective study aimed to clarify the characteristics, diagnostic accuracy, treatment outcomes, and prognostic factors of uterine serous carcinoma (USC) in Japanese women. Methods: The medical records of 193 patients who were treated between 2006 and 2008 at 24 participating institutions in the Japanese Clinical Oncology Group were examined, and pathological slides of 188 patients were re-checked through central pathology review (CPR), hematoxylin-eosin staining, and immunohistochemistry. Results: USC was confirmed in 144 of the 188 (76.6%) patients using CPR, and only 50% were correctly diagnosed preoperatively. Forty-three patients were diagnosed with non-serous carcinoma, whereas one patient had metastasis from another organ. The average age was 65.7 years, and 19% of patients had a history of other cancers. The incidence of stage III–IV disease was 52.8%, and lymph node metastasis was found in 28.5% of patients. Extrauterine spread and distant metastasis occurred in 39% and 14% of patients, respectively. The 2-year overall survival and progression-free survival (PFS) rates were 56% and 42%, respectively. The PFS of patients with stage I and II who underwent complete staging surgery was 92.3%, and that of those without lymph node dissection or omentectomy was 33.3%. Patients with USC had a significantly worse prognosis than 43 patients with non-serous carcinoma. Conclusion USC in Japanese women has characteristics different from those of endometrioid carcinoma, worse prognosis, and is difficult to diagnose preoperatively. Complete surgical staging is necessary even for early-stage disease. Additionally, new adjuvant treatment strategies, including molecular targeted therapy, should be explored.

We developed three e-learning systems for endoscopists to acquire the necessary skills to improve the diagnosis of early gastric cancer (EGC) and demonstrated their usefulness using randomized controlled trials. The subjects of the three e-learning systems were “detec­tion”, “characterization”, and “preoperative assessment”. The contents of each e-learning system included “technique”, “knowledge”, and “obtaining experience”. All e-learning systems proved useful for endoscopists to learn how to diagnose EGC. Lecture videos describing “the technique” and “the knowledge” can be beneficial. In addition, repeating 100 self-study cases allows learners to gain “experience” and improve their diagnostic skills further. Web-based e-learning systems have more advantages than other teaching methods because the number of participants is unlimited. Histopathological diagnosis is the gold standard for the diagnosis of gastric cancer. Therefore, we developed a comprehensive diagnostic algorithm to standardize the histopathological diagnosis of gastric cancer. Once we have successfully shown that this algorithm is helpful for the accurate histopathological diagnosis of cancer, we will complete a series of e-learning systems designed to assess EGC accurately.

Background: /Aim: The aim of this study was to compare the therapeutic efficacy of ablation and surgery in solitary hepatocellular carcinoma (HCC) measuring ≤5 cm with a large HCC cohort database. Methods: The study included consecutive 2,067 patients with solitary HCC who were treated with either ablation (n=1,248) or surgery (n=819). Th e patients were divided into three groups based on the tumor size and compared the outcomes of the two therapies using propensity score matching. Results: No significant difference in recurrence-free survival (RFS) or overall survival (OS) was found between surgery and ablation groups for tumors measuring ≤2 cm or >2 cm but ≤3 cm. For tumors measuring >3 cm but ≤5 cm, RFS was significantly better with surgery than with ablation (3.6 and 2.0 years, respectively, P=0.0297). However, no significant difference in OS was found between surgery and ablation in this group (6.7 and 6.0 years, respectively, P=0.668). Conclusion The study suggests that surgery and ablation can be equally used as a treatment for solitary HCC no more than 3 cm in diameter. For HCCs measuring 3-5 cm, the OS was not different between therapies; thus, ablation and less invasive therapy can be considered a treatment option; however, special caution should be taken to prevent recurrence.

Background/Aims: Image-enhanced endoscopy can detect superficial oro-hypopharyngeal squamous cell carcinoma; however, reliable endoscopy of the pharyngeal region is challenging. Endoscopy under general anesthesia during transoral surgery occasionally reveals multiple synchronous lesions that remained undetected on preoperative endoscopy. Therefore, we aimed to determine the lesion detection capability of endoscopy under general anesthesia for superficial oro-hypopharyngeal squamous cell carcinoma. Methods: This retrospective study included 63 patients who underwent transoral surgery for superficial oropharyngeal squamous cell carcinoma between April 2005 and December 2020. The primary endpoint was to compare the lesion detection capabilities of preoperative endoscopy and endoscopy under general anesthesia. Other endpoints included the comparison of clinicopathological findings between lesions detected using preoperative endoscopy and those newly detected using endoscopy under general anesthesia. Results: Fifty-eight patients (85 lesions) were analyzed. The mean number of lesions per patient detected was 1.17 for preoperative endoscopy and 1.47 for endoscopy under general anesthesia. Endoscopy under general anesthesia helped detect more lesions than preoperative endoscopy did (p<0.001). The lesions that were newly detected on endoscopy under general anesthesia were small and characterized by few changes in color and surface ruggedness. Conclusions Endoscopy under general anesthesia for superficial squamous cell carcinoma is helpful for detecting multiple synchronous lesions.

Background/Aims: Several studies have assessed the effect of cool temperature on colonic peristalsis. Transient receptor potential melastatin 8 (TRPM8) is a temperature-sensitive ion channel activated by mild cooling expressed in the colon. We examined the antispasmodic effect of cool temperature on colonic peristalsis in a prospective, randomized, single-blind trial and based on the video imaging and intraluminal pressure of the proximal colon in rats and TRPM8-deficient mice. Methods: In the clinical trial, we randomly assigned a total of 94 patients scheduled to undergo colonoscopy to 2 groups: the mildly cool water (n = 47) and control (n = 47) groups. We used 20 mL of 15°C water for the mildly cool water. The primary outcome was the proportion of subjects with improved peristalsis after treatment. In the rodent proximal colon, we evaluated the intraluminal pressure and performed video imaging of the rodent proximal colon with cool water administration into the colonic lumen. Clinical trial registry website (Trial No. UMIN-CTR; UMIN000030725). Results: In the randomized controlled trial, after treatment, the proportion of subjects with no peristalsis with cool water was significantly higher than that in the placebo group (44.7% vs 23.4%; P < 0.05). In the rodent colon model, cool temperature water was associated with a significant decrease in colonic peristalsis through its suppression of the ratio of peak frequency (P < 0.05). Cool temperaturetreated TRPM8-deficient mice did not show a reduction in colonic peristalsis compared with wild-type mice. Conclusion For the first time, this study demonstrates that cool temperature-dependent suppression of colonic peristalsis may be associated with TRPM8 activation.

Objective: In late 1970s, occupational exposure to antineoplastic agents was reported. Various countries, including Japan, have published guidelines for handling antineoplastic agents. Surveys are still being conducted to determine the levels of environmental exposure to antineoplastic agents at individual hospitals, and incidents of contamination are often reported. This study provides details regarding a literature survey conducted to evaluate the actual state of environmental contamination by antineoplastic agents and identify the related issues in order to promote environmental monitoring.Methods: The literature search was carried out from January 1, 1990 to July 31, 2017. PubMed and Ichushi-Web were searched with the following keywords: “antineoplastic agents,” “occupational exposure,” “surface contamination,” and “environmental monitoring.”Results: Following the literature search, 117 papers were included in the analysis. The findings showed that contamination by antineoplastic agents was widely reported in hospitals and places where antineoplastic drugs were not handled. The findings of this study regarding the actual state of environmental exposure are partial, as there is a lack of information on retail pharmacies and homes of outpatients who have received chemotherapy.Discussion: Therefore, further investigation is warranted. In addition, according to the current Japanese guidelines, published in 2015, environmental surveillance is not required to reduce contamination by antineoplastic agents. To promote environmental monitoring, we feel that it is necessary to determine a new survey method and the clarify optimum interval of environmental monitoring.

BACKGROUND: Sedentary behaviors have recently become an important public health issue. We aimed to investigate the relationship between screen time and nutrient intake in children and adolescents. METHODS: The present study was conducted in 2013. Data were collected from children and adolescents aged between 6 and 15 years old in Shika town. Questionnaires were distributed to 1459 subjects, 1414 of whom participated in the study (96.9%). Sedentary behaviors were assessed based on participants' screen behaviors (television (TV) viewing, personal computer (PC) use, and mobile phone (MP) use). The main outcomes were the intake of nutrients from a validated food frequency questionnaire. Analysis of covariance (ANCOVA) was used to examine the significance of differences in nutrient intake estimates. Multivariate linear regression analyses, adjusting for age, BMI, and physical activity, were used to provide parameter estimates (β) and 95% CI for the relationship between screen time and nutrient intake. RESULTS: In boys, longer TV viewing times correlated or tended to correlate with a lower intake of protein, potassium, calcium, iron, vitamin K, vitamin B-2, and total dietary fiber. In girls, longer TV viewing times correlated with a lower intake of protein, sodium, calcium, vitamin D, and vitamin B-2. Longer TV viewing times correlated with a higher intake of n-6 fatty acids in girls. PC use was related or tended to be related to a lower intake of potassium, iron, vitamin K, and folic acid in boys, but not in girls. A relationship was observed between MP use and a lower intake of vitamin K in boys, and MP use and a higher intake of vitamin D in girls. CONCLUSIONS The present results revealed that longer TV viewing times are associated with less protein, minerals, vitamins, and total dietary fiber intake in children and adolescents. It was also revealed that boys with PC use have less minerals and vitamins. These results support the need to design intervention programs that focus on decreasing TV viewing time in both sexes and PC use in boys while encouraging adherence to dietary guidelines among children and adolescents.
Adolescent ; Body Mass Index ; Child ; Cross-Sectional Studies ; Diet ; Energy Intake ; Exercise ; Female ; Humans ; Japan ; Male ; Screen Time ; Sedentary Behavior ; Sex Factors ; Socioeconomic Factors

BACKGROUND/AIMS: Colonic diverticular hemorrhage (DH) was a rare disease until the 1990s, and its incidence has increased rapidly since 2000 in Japan. In recent years, colonic DH has been the most frequent cause of lower gastrointestinal bleeding (LGIB). Nearly all cases of DH are mild, with the bleeding often stopping spontaneously. Some cases, however, require surgery or arterial embolization. In this study, using a cohort at Fukuoka University Chikushi Hospital, we investigated factors associated with severe colonic DH. METHODS: Among patients with LGIB who underwent colonoscopy at our hospital between 1995 and 2013, DH was identified in 273 patients. Among them, 62 patients (22.7%) were defined as having severe colonic DH according to recurrence of bleeding in a short period, and/or the necessity of transfusion, arterial embolization, or surgery. We then evaluated risk factors for severe DH among DH patients in this retrospective cohort. RESULTS: Among the 273 patients with DH, use of non-steroidal anti-inflammatory drugs (NSAIDs) (odds ratio [OR], 2.801; 95% confidence interval [CI], 1.164–6.742), Charlson Risk Index (CRI) ≥2 (OR, 3.336; 95% CI, 1.154–7.353), right-sided colonic DH (OR, 3.873; 95% CI, 1.554–9.653), and symptoms of cerebral hypoperfusion (such as light-headedness, dizziness, or syncope) (OR, 2.926; 95% CI, 1.310–6.535) showed an increased risk of severe DH even after controlling for other factors. CONCLUSIONS: Severe DH occurred in 23% of DH patients, and NSAID use, CRI ≥2, right-sided colonic DH, and symptoms of cerebral hypoperfusion are suggested to be predictors of severe DH.
Anti-Inflammatory Agents, Non-Steroidal ; Cohort Studies ; Colon* ; Colonoscopy ; Dizziness ; Hemorrhage* ; Humans ; Incidence ; Japan ; Rare Diseases ; Recurrence ; Retrospective Studies ; Risk Factors*