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.

BACKGROUND: SARS-CoV-2 (COVID-19) is transmitted via infectious respiratory particles. Infectious respiratory particles are released when an infected person breathes, coughs, or speaks. Several studies have measured respiratory particle concentrations through focusing on activities such as breathing, coughing, and short speech. However, few studies have investigated the effect of speech duration. METHODS: This study aimed to clarify the effects of speech duration and volume on the respiratory particle concentration. Study participants were requested to speak at three voice volumes across five speech durations, generating 15 speech patterns. Participants spoke inside a clean booth where particle concentrations and voice volumes were measured and analyzed during speech. RESULTS: Our findings suggest that as speech duration increased, the aerosol number concentration also increased. Through focusing on individual differences, we considered there might be super-emitters who emit more aerosol particles than the average human. Two participants were identified as statistical outliers (aerosol number concentration, n = 1; mass concentration, n = 1). CONCLUSIONS Considering speech duration may improve our understanding of respiratory particle concentration dynamics. Two participants were identified as potential super-emitters.
Humans ; Male ; Speech/physiology* ; Adult ; Female ; COVID-19/transmission* ; Respiratory Aerosols and Droplets ; Voice ; SARS-CoV-2 ; Time Factors ; Young Adult ; Aerosols/analysis*

Objective: To evaluate the long-term efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer. Methods: This was the follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with homologous recombination-deficient, platinum-sensitive, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who had completed 3–4 lines of chemotherapy and were poly(ADP-ribose) polymerase inhibitor naïve. Participants received niraparib (starting dose, 300 mg) once daily in continuous 28-day cycles until objective disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was confirmed objective response rate (ORR), as assessed using Response Evaluation Criteria in Solid Tumors version 1.1. Safety evaluations included treatment-emergent adverse events (TEAEs). Results: 20 patients were enrolled in the study and included in both efficacy and safety analyses. Median total study duration was 759.5 days. Median dose intensity was 201.3 mg/ day. Confirmed ORR was 60.0% (90% confidence interval [CI]=39.4–78.3); 2 patients had complete response and 10 patients had partial response. Median duration of response was 9.9 months (95% CI=3.9–26.9) and the disease control rate was 90.0% (95% CI=68.3–98.8).The most common TEAEs were anemia (n=15), nausea (n=12), and decreased platelet count (n=11). TEAEs leading to study drug dose reduction, interruption, or discontinuation were reported in 16 (80.0%), 15 (75.0%), and 2 patients (10.0%), respectively. Conclusion The long-term efficacy and safety profile of niraparib was consistent with previous findings in the equivalent population in non-Japanese patients. No new safety signals were identified.

Objective: To evaluate the long-term efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer. Methods: This was the follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with homologous recombination-deficient, platinum-sensitive, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who had completed 3–4 lines of chemotherapy and were poly(ADP-ribose) polymerase inhibitor naïve. Participants received niraparib (starting dose, 300 mg) once daily in continuous 28-day cycles until objective disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was confirmed objective response rate (ORR), as assessed using Response Evaluation Criteria in Solid Tumors version 1.1. Safety evaluations included treatment-emergent adverse events (TEAEs). Results: 20 patients were enrolled in the study and included in both efficacy and safety analyses. Median total study duration was 759.5 days. Median dose intensity was 201.3 mg/ day. Confirmed ORR was 60.0% (90% confidence interval [CI]=39.4–78.3); 2 patients had complete response and 10 patients had partial response. Median duration of response was 9.9 months (95% CI=3.9–26.9) and the disease control rate was 90.0% (95% CI=68.3–98.8).The most common TEAEs were anemia (n=15), nausea (n=12), and decreased platelet count (n=11). TEAEs leading to study drug dose reduction, interruption, or discontinuation were reported in 16 (80.0%), 15 (75.0%), and 2 patients (10.0%), respectively. Conclusion The long-term efficacy and safety profile of niraparib was consistent with previous findings in the equivalent population in non-Japanese patients. No new safety signals were identified.

Objective: To evaluate the long-term efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer. Methods: This was the follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with homologous recombination-deficient, platinum-sensitive, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who had completed 3–4 lines of chemotherapy and were poly(ADP-ribose) polymerase inhibitor naïve. Participants received niraparib (starting dose, 300 mg) once daily in continuous 28-day cycles until objective disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was confirmed objective response rate (ORR), as assessed using Response Evaluation Criteria in Solid Tumors version 1.1. Safety evaluations included treatment-emergent adverse events (TEAEs). Results: 20 patients were enrolled in the study and included in both efficacy and safety analyses. Median total study duration was 759.5 days. Median dose intensity was 201.3 mg/ day. Confirmed ORR was 60.0% (90% confidence interval [CI]=39.4–78.3); 2 patients had complete response and 10 patients had partial response. Median duration of response was 9.9 months (95% CI=3.9–26.9) and the disease control rate was 90.0% (95% CI=68.3–98.8).The most common TEAEs were anemia (n=15), nausea (n=12), and decreased platelet count (n=11). TEAEs leading to study drug dose reduction, interruption, or discontinuation were reported in 16 (80.0%), 15 (75.0%), and 2 patients (10.0%), respectively. Conclusion The long-term efficacy and safety profile of niraparib was consistent with previous findings in the equivalent population in non-Japanese patients. No new safety signals were identified.

We report a case of a 72-year-old woman with a tumor arising from a colostomy site that had been created 25 years earlier when rectal amputation was performed for perforated sigmoid cancer. She was referred to our hospital due to complaints of pain from the colostomy. The diagnosis was carcinoma arising at the colostomy site with lymph node metastasis. Laparoscopic surgery was performed by attaching an Applied Alexis® wound retractor to the incision site of the colostomy. Lymph node dissection was performed and the left hemicolon was resected. Carcinoma arising from a colostomy site is rare. Laparoscopic surgery was considered to be a useful procedure because it allows for lymph node dissection and intestinal mobilization with minimal invasiveness.

A chest X-ray taken during a medical checkup for a 75-year-old man revealed a nodular shadow in the right middle lung field. Chest computed tomography (CT) for further examination showed an intra-abdominal tumor as an additional finding, and the patient was referred to our department. Contrast-enhanced CT revealed a tumor (16×10×5 cm) in the left upper to middle abdomen. The tumor had a clear border and uniform fat density inside. It compressed the stomach to the ventral side, but the patient had no subjective symptoms. Magnetic resonance imaging also showed the tumor contained a uniform fatty component inside, as well as no obvious non-fatty components. An intra-abdominal lipoma was suspected, but the possibility of a welldifferentiated liposarcoma could not be ruled out due to its size. During curative surgery, intraoperative findings revealed a soft tumor, weighing 612 g, with a well-defined border in the mesentery of the transverse colon. Pathological findings showed proliferation of mature adipocytes without malignancy. We report here this case of mesenteric lipoma, a rare intraabdominal tumor, and review the relevant literature.

A 57-year-old man was admitted to our hospital with adhesive bowel obstruction following pancreaticoduodenectomy performed for cholangiocarcinoma 4 months earlier. After admission, the patient remained nil per os and was closely observed. On the third day of admission, he developed worsening abdominal pain, and computed tomography revealed strangulation of the small intestinal mesentery dorsal to the superior mesenteric artery, with prolapse of the small intestine into the right upper quadrant to form a closed loop. Strangulated bowel obstruction secondary to internal hernia was diagnosed, and he underwent emergency surgery. Intraoperatively, we detected a hernia orifice formed by the mesentery and peritoneum at the site of the defect following resection of the ligament of Treitz, and we observed that approximately 2 m of the small intestine had prolapsed into the right upper quadrant. The herniated intestine was returned to the abdominal cavity, and the hernia orifice was sutured following hernia reduction. Few reports have described an internal hernia after pancreaticoduodenectomy; however, it has been reported that this operation can result in various types of internal hernia because of the complicated reconstructive procedure. Here we report our findings in this unique case together with a literature review.

The patient was an 80-year-old man who was diagnosed with cStage IIIB non-small cell lung cancer (NSCLC) and early gastric cancer. The advanced lung cancer was treated with chemotherapy while the gastric cancer was monitored. Immune checkpoint inhibitors were effective against the lung cancer for a long period, but new gastric cancer appeared and progressed to an advanced stage, necessitating total gastrectomy 5 years after the diagnosis of NSCLC. The patient is currently being treated with a molecular targeted agent for progression of the lung cancer after gastrectomy. In the future, the number of cases with multiple primary cancers will increase alongside aging of the population and advances in cancer treatment, and a system for tumor-agnostic treatment selection and medical treatment will be necessary.

A 63-year-old man was admitted to our hospital in March 2017 with dysphagia and right homonymous hemianopsia. We diagnosed him with esophagogastric junction cancer (adenocarcinoma) with metastases to the cerebral occipital lobe, bone, and lymph nodes. After one cycle of 5FU + cisplatin (FP), the brain metastasis was resected because of the hemiplegic symptoms he developed. Histology of the resected tissue showed no viable tumor cells. After three cycles of FP, the primary lesion and metastases were resolved. Upper gastrointestinal endoscopy revealed a scar at the primary site. This was considered a complete response (CR). In April 2018, CT revealed a mass at the cardia, which was considered as lymph node metastases with gastric wall invasion. Although two additional cycles of FP were administered for recurrent tumors, the efficacy was progressive. In August 2018, proximal gastrectomy and D1 + lymph node dissection were performed. The pathological diagnosis was gastric intramural metastases and lymph node metastases (ypN1 [2/22]). Weekly paclitaxel therapy was administered for three months after surgery. Two years have passed since the last surgery without recurrence. We report a rare case of esophagogastric junction cancer with brain, bone, and gastric intramural metastases that responded to combined modality therapy.