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Objectives The objective of this study was to compare the incidence rates (IRs) of infectious diseases, major adverse cardiovascular events (MACEs), and malignancies in RA patients treated with tofacitinib, baricitinib or a TNF inhibitor. Methods We retrospectively analysed the cases of 499 RA patients treated with tofacitinib (n  = 192), baricitinib (n  = 104), or a TNF inhibitor (n  = 203). We determined the IRs of infectious diseases and the standardized incidence ratio (SIR) of malignancies and investigated factors related to infectious diseases. After adjusting the clinical characteristic imbalance by propensity score weighting, we compared the incidence of adverse events between the Janus kinase (JAK)-inhibitor and TNF-inhibitor groups. Results The observational period was 959.7 patient-years (PY), and the median observational period was 1.3 years. The IRs within the JAK-inhibitor treatment group were: serious infectious diseases other than herpes zoster (HZ), 8.36/100 PY; HZ, 13.00/100 PY. Multivariable Cox regression analyses revealed independent risk factors: the glucocorticoid dose in serious infectious diseases other than HZ, and older age in HZ. Two MACEs and 11 malignancies were identified in JAK-inhibitor–treated patients. The overall malignancy SIR was (non-significantly) higher than that of the general population (1.61/100 PY, 95% CI: 0.80, 2.88). The IR of HZ in the JAK-inhibitor–treated group was significantly higher than the TNF-inhibitor-treated group, but there were no significant differences in the IRs of other adverse events between the JAK-inhibitor–treated group and the TNF-inhibitor–treated group, or between the treatment groups of the two JAK inhibitors. Conclusions The infectious disease IR in RA was comparable between tofacitinib and baricitinib, but the IR for HZ in these treatment groups was high compared with that in the TNF inhibitor treatment group. The malignancy rate in the JAK-inhibitor-treated group was high but not significantly different from that of the general population or that of the TNF-inhibitor–treated group. [ABSTRACT FROM AUTHOR]

Aim: Laparoscopic power morcellator (LPM) can be used for tissue retrieval through laparoscopic port site, but the dissemination of uterine and/or myoma tissues is a serious complication. To study the use of LPM for uterine fibroid treatment in Japan, we aimed to perform two national cross‐sectional surveys comprising multiple questionnaires. Methods: The first survey (2011–2013) was conducted in November 2014, and 203 medical institutions responded. The second survey (2017–2019) was conducted in December 2020, and 302 medical institutions were investigated. Results: Overall, 72 104 and 120 425 surgeries and 0.04% and 0.05% cases of postoperative malignancy diagnosis were reported in the first and second surveys, respectively. Magnetic resonance imaging was performed in >90% of the cases in the first and second surveys as preoperative examinations. The frequency of LPM at hysterectomy was 8.9% and 4.6% and the frequency of LPM at laparoscopic myomectomy was 80.4% and 54.8% in the first and second surveys, respectively; both the parameters decreased in the second survey. Conclusions: It is impossible to completely exclude malignant diseases even if extensive preoperative diagnosis has been done before surgery. Therefore, the use of LPM in patients requires careful attention and informed consent in Japan. [ABSTRACT FROM AUTHOR]

The link between inflammation and cancer survival has been the subject of substantial research. The goal of this review is to summarize the evidence on the prognostic value of systemic inflammation score (SIS) in esophageal cancer patients undergoing surgical intervention. PubMed, Scopus, Embase, and Web of Science were searched for relevant articles published until 30th June 2022. We pooled adjusted data on overall survival (OS) and disease-free survival (DFS) using a random-effects meta-analysis model. The review was pre-registered on PROSPER (No. CRD42022340717). Eight studies were included. All studies were conducted either in China or Japan. Six studies showed that patients with SIS of 1-2 had poor OS as compared to those with scores of 0 (HR:1.42 95% CI: 1.24, 1.62 I2=25%). SIS of 1 (HR:1.45 95% CI: 1.18, 1.78 I2=0%) and 2 (HR:1.94 95% CI: 1.49, 2.53 I2=0%) were also associated with poor OS. Two studies compared the SIS score of 2 vs 0-1. Meta-analysis indicated that poor OS was associated with SIS of 2 (HR:1.80 95% CI: 1.25, 2.58). Data from three studies showed that the SIS score did not predict DFS (HR:1.40 95% CI: 0.82, 2.39 I2=91%). SIS can be a novel prognostic indicator for esophageal cancer patients undergoing surgical intervention. Higher SIS is associated with a poor OS, but it does not predict DFS. Future studies are needed to strengthen the current evidence. [ABSTRACT FROM AUTHOR]

Introduction: The evolution of disease-modifying antirheumatic drugs (DMARDs) for the treatment of rheumatoid arthritis (RA) has improved patient prognosis. However, more real-world safety/effectiveness data comparing methotrexate (MTX), tofacitinib, tumor necrosis factor inhibitors (TNFi), and non-TNFi biologic DMARDs (bDMARDs) are warranted.The CorEvitas RA Japan registry was used to identify patients with rheumatologist-diagnosed RA who initiated MTX/tofacitinib/TNFi/non-TNFi bDMARDs. Safety outcomes included incidence of major adverse cardiovascular events (MACE), total cardiovascular disease, total serious infections, total herpes zoster, and total malignancies (excluding non-melanoma skin cancer). Effectiveness outcomes included change from baseline (Δ) in Clinical Disease Activity Index (CDAI) and proportion of patients achieving a minimum clinically important difference (MCID) in CDAI at month 6. Adjusted regression models were fit; marginal means were estimated.Overall, 1972 patients were included in the safety cohort: MTX (N = 298); tofacitinib (N = 253); TNFi (N = 663); non-TNFi (N = 758). Mean follow-up time was 3.8, 2.9, 3.0, and 2.9 years for MTX, tofacitinib, TNFi, and non-TNFi, respectively. Adjusted incidence rates (IRs, patients with events/100 patient-years [95% confidence intervals]) for MACE and total cardiovascular disease, respectively, were numerically lower for MTX (0.34 [0, 0.83]; 0.42 [0, 0.92]) and TNFi (0.09 [0, 0.27]; 0.61 [0.15, 1.07]) versus tofacitinib (0.48 [0, 1.20]; 2.30 [0.38, 4.22]) and non-TNFi (0.77 [0.35, 1.19]; 1.28 [0.73, 1.82]). Serious infections were numerically higher for non-TNFi (4.47 [3.38, 5.56]); herpes zoster was higher for tofacitinib (7.41 [4.52, 10.29]), versus other groups. IRs for malignancies were comparable between groups. Mean ΔCDAI and rates of achieving MCID in CDAI at month 6 were generally greater with tofacitinib versus other groups.Some variations in incidence of safety outcomes were observed between treatments, while certain effectiveness outcomes favored tofacitinib. Sample size variation between groups and low number of safety events limited the analysis. Further studies are warranted to investigate observed differences.NCT05572567.Methods: The evolution of disease-modifying antirheumatic drugs (DMARDs) for the treatment of rheumatoid arthritis (RA) has improved patient prognosis. However, more real-world safety/effectiveness data comparing methotrexate (MTX), tofacitinib, tumor necrosis factor inhibitors (TNFi), and non-TNFi biologic DMARDs (bDMARDs) are warranted.The CorEvitas RA Japan registry was used to identify patients with rheumatologist-diagnosed RA who initiated MTX/tofacitinib/TNFi/non-TNFi bDMARDs. Safety outcomes included incidence of major adverse cardiovascular events (MACE), total cardiovascular disease, total serious infections, total herpes zoster, and total malignancies (excluding non-melanoma skin cancer). Effectiveness outcomes included change from baseline (Δ) in Clinical Disease Activity Index (CDAI) and proportion of patients achieving a minimum clinically important difference (MCID) in CDAI at month 6. Adjusted regression models were fit; marginal means were estimated.Overall, 1972 patients were included in the safety cohort: MTX (N = 298); tofacitinib (N = 253); TNFi (N = 663); non-TNFi (N = 758). Mean follow-up time was 3.8, 2.9, 3.0, and 2.9 years for MTX, tofacitinib, TNFi, and non-TNFi, respectively. Adjusted incidence rates (IRs, patients with events/100 patient-years [95% confidence intervals]) for MACE and total cardiovascular disease, respectively, were numerically lower for MTX (0.34 [0, 0.83]; 0.42 [0, 0.92]) and TNFi (0.09 [0, 0.27]; 0.61 [0.15, 1.07]) versus tofacitinib (0.48 [0, 1.20]; 2.30 [0.38, 4.22]) and non-TNFi (0.77 [0.35, 1.19]; 1.28 [0.73, 1.82]). Serious infections were numerically higher for non-TNFi (4.47 [3.38, 5.56]); herpes zoster was higher for tofacitinib (7.41 [4.52, 10.29]), versus other groups. IRs for malignancies were comparable between groups. Mean ΔCDAI and rates of achieving MCID in CDAI at month 6 were generally greater with tofacitinib versus other groups.Some variations in incidence of safety outcomes were observed between treatments, while certain effectiveness outcomes favored tofacitinib. Sample size variation between groups and low number of safety events limited the analysis. Further studies are warranted to investigate observed differences.NCT05572567.Results: The evolution of disease-modifying antirheumatic drugs (DMARDs) for the treatment of rheumatoid arthritis (RA) has improved patient prognosis. However, more real-world safety/effectiveness data comparing methotrexate (MTX), tofacitinib, tumor necrosis factor inhibitors (TNFi), and non-TNFi biologic DMARDs (bDMARDs) are warranted.The CorEvitas RA Japan registry was used to identify patients with rheumatologist-diagnosed RA who initiated MTX/tofacitinib/TNFi/non-TNFi bDMARDs. Safety outcomes included incidence of major adverse cardiovascular events (MACE), total cardiovascular disease, total serious infections, total herpes zoster, and total malignancies (excluding non-melanoma skin cancer). Effectiveness outcomes included change from baseline (Δ) in Clinical Disease Activity Index (CDAI) and proportion of patients achieving a minimum clinically important difference (MCID) in CDAI at month 6. Adjusted regression models were fit; marginal means were estimated.Overall, 1972 patients were included in the safety cohort: MTX (N = 298); tofacitinib (N = 253); TNFi (N = 663); non-TNFi (N = 758). Mean follow-up time was 3.8, 2.9, 3.0, and 2.9 years for MTX, tofacitinib, TNFi, and non-TNFi, respectively. Adjusted incidence rates (IRs, patients with events/100 patient-years [95% confidence intervals]) for MACE and total cardiovascular disease, respectively, were numerically lower for MTX (0.34 [0, 0.83]; 0.42 [0, 0.92]) and TNFi (0.09 [0, 0.27]; 0.61 [0.15, 1.07]) versus tofacitinib (0.48 [0, 1.20]; 2.30 [0.38, 4.22]) and non-TNFi (0.77 [0.35, 1.19]; 1.28 [0.73, 1.82]). Serious infections were numerically higher for non-TNFi (4.47 [3.38, 5.56]); herpes zoster was higher for tofacitinib (7.41 [4.52, 10.29]), versus other groups. IRs for malignancies were comparable between groups. Mean ΔCDAI and rates of achieving MCID in CDAI at month 6 were generally greater with tofacitinib versus other groups.Some variations in incidence of safety outcomes were observed between treatments, while certain effectiveness outcomes favored tofacitinib. Sample size variation between groups and low number of safety events limited the analysis. Further studies are warranted to investigate observed differences.NCT05572567.Conclusion: The evolution of disease-modifying antirheumatic drugs (DMARDs) for the treatment of rheumatoid arthritis (RA) has improved patient prognosis. However, more real-world safety/effectiveness data comparing methotrexate (MTX), tofacitinib, tumor necrosis factor inhibitors (TNFi), and non-TNFi biologic DMARDs (bDMARDs) are warranted.The CorEvitas RA Japan registry was used to identify patients with rheumatologist-diagnosed RA who initiated MTX/tofacitinib/TNFi/non-TNFi bDMARDs. Safety outcomes included incidence of major adverse cardiovascular events (MACE), total cardiovascular disease, total serious infections, total herpes zoster, and total malignancies (excluding non-melanoma skin cancer). Effectiveness outcomes included change from baseline (Δ) in Clinical Disease Activity Index (CDAI) and proportion of patients achieving a minimum clinically important difference (MCID) in CDAI at month 6. Adjusted regression models were fit; marginal means were estimated.Overall, 1972 patients were included in the safety cohort: MTX (N = 298); tofacitinib (N = 253); TNFi (N = 663); non-TNFi (N = 758). Mean follow-up time was 3.8, 2.9, 3.0, and 2.9 years for MTX, tofacitinib, TNFi, and non-TNFi, respectively. Adjusted incidence rates (IRs, patients with events/100 patient-years [95% confidence intervals]) for MACE and total cardiovascular disease, respectively, were numerically lower for MTX (0.34 [0, 0.83]; 0.42 [0, 0.92]) and TNFi (0.09 [0, 0.27]; 0.61 [0.15, 1.07]) versus tofacitinib (0.48 [0, 1.20]; 2.30 [0.38, 4.22]) and non-TNFi (0.77 [0.35, 1.19]; 1.28 [0.73, 1.82]). Serious infections were numerically higher for non-TNFi (4.47 [3.38, 5.56]); herpes zoster was higher for tofacitinib (7.41 [4.52, 10.29]), versus other groups. IRs for malignancies were comparable between groups. Mean ΔCDAI and rates of achieving MCID in CDAI at month 6 were generally greater with tofacitinib versus other groups.Some variations in incidence of safety outcomes were observed between treatments, while certain effectiveness outcomes favored tofacitinib. Sample size variation between groups and low number of safety events limited the analysis. Further studies are warranted to investigate observed differences.NCT05572567.ClinicalTrials.gov: The evolution of disease-modifying antirheumatic drugs (DMARDs) for the treatment of rheumatoid arthritis (RA) has improved patient prognosis. However, more real-world safety/effectiveness data comparing methotrexate (MTX), tofacitinib, tumor necrosis factor inhibitors (TNFi), and non-TNFi biologic DMARDs (bDMARDs) are warranted.The CorEvitas RA Japan registry was used to identify patients with rheumatologist-diagnosed RA who initiated MTX/tofacitinib/TNFi/non-TNFi bDMARDs. Safety outcomes included incidence of major adverse cardiovascular events (MACE), total cardiovascular disease, total serious infections, total herpes zoster, and total malignancies (excluding non-melanoma skin cancer). Effectiveness outcomes included change from baseline (Δ) in Clinical Disease Activity Index (CDAI) and proportion of patients achieving a minimum clinically important difference (MCID) in CDAI at month 6. Adjusted regression models were fit; marginal means were estimated.Overall, 1972 patients were included in the safety cohort: MTX (N = 298); tofacitinib (N = 253); TNFi (N = 663); non-TNFi (N = 758). Mean follow-up time was 3.8, 2.9, 3.0, and 2.9 years for MTX, tofacitinib, TNFi, and non-TNFi, respectively. Adjusted incidence rates (IRs, patients with events/100 patient-years [95% confidence intervals]) for MACE and total cardiovascular disease, respectively, were numerically lower for MTX (0.34 [0, 0.83]; 0.42 [0, 0.92]) and TNFi (0.09 [0, 0.27]; 0.61 [0.15, 1.07]) versus tofacitinib (0.48 [0, 1.20]; 2.30 [0.38, 4.22]) and non-TNFi (0.77 [0.35, 1.19]; 1.28 [0.73, 1.82]). Serious infections were numerically higher for non-TNFi (4.47 [3.38, 5.56]); herpes zoster was higher for tofacitinib (7.41 [4.52, 10.29]), versus other groups. IRs for malignancies were comparable between groups. Mean ΔCDAI and rates of achieving MCID in CDAI at month 6 were generally greater with tofacitinib versus other groups.Some variations in incidence of safety outcomes were observed between treatments, while certain effectiveness outcomes favored tofacitinib. Sample size variation between groups and low number of safety events limited the analysis. Further studies are warranted to investigate observed differences.NCT05572567. [ABSTRACT FROM AUTHOR]

Background and Aim: To clarify the clinicoepidemiological characteristics of immunoglobulin G4 (IgG4)‐related disease (IgG4‐RD) with malignancy, a nationwide epidemiological survey was conducted. Methods: Immunoglobulin G4‐related disease patients with malignancy who had visited selected hospitals in Japan were surveyed. The study consisted of two stages: the number of IgG4‐RD patients with malignancy was estimated by the first questionnaire and their clinicoepidemiological characteristics were assessed by the second questionnaire. Results: The frequencies of autoimmune pancreatitis (AIP), IgG4‐related sialadenitis, IgG4‐related eye disease, IgG4‐related kidney disease, and IgG4‐related retroperitoneal fibrosis were 44.7%, 20.8%, 14.0%, 5.16%, and 5.12%, respectively. The overall prevalence of malignant disease in IgG4‐RD cases was estimated to be 10 900 per 100 000 cases, which was significantly higher than that of malignant disease in the general population. The prevalence of malignant lymphoma in IgG4‐RD cases was the highest and was estimated to be 1985 per 100 000 cases. IgG4‐related kidney disease had the highest frequency of malignant disease (17.1%). In data from 200 patients, 61 (30.5%) cases of cancer were found 2 years or more before the IgG4‐RD diagnosis, 92 cases (46%) during the 1 year preceding or following IgG4‐RD diagnosis, and 62 cases of cancer (31%) 2 or more years following IgG4‐RD diagnosis. Conclusions: The nationwide survey for IgG4‐RD with malignancy in Japan showed that IgG4‐RD may be related with malignant diseases. [ABSTRACT FROM AUTHOR]

Background: Malignancy after kidney transplantation (KT) is one of the most serious post-transplant complications. This study aimed to investigate the incidence, type, and outcomes of malignancy after pediatric KT. Methods: We performed a retrospective cohort study on pediatric kidney transplant recipients aged 18 years or younger who received their first transplant between 1975 and 2009. Results: Among the 375 children who underwent KT, 212 were male (56.5%) and 163 were female (43.5%) (median age at KT, 9.6 years [interquartile range {IQR}] 5.8–12.9 years). The incidence of malignancy was 5.6% (n = 21). The cumulative incidences of cancer were 0.8%, 2.5%, 2.8%, 4.2%, 5.5%, and 15.6% at 1, 5, 10, 15, 20, and 30 years post-transplantation, respectively. Of 375 patients, 12 (3.2%) had solid cancer and nine (2.4%) had lymphoproliferative malignancy. The median age at the first malignancy was 21.3 years (IQR 11.5–33.3 years). The median times from transplant to diagnosis were 22.3 years (IQR 12.3–26.6 years) for solid cancer and 2.2 years (IQR 0.6–2.8) for lymphoproliferative malignancies. During follow-up, five recipients died due to malignancy. The causes of death were hepatocellular carcinoma in one patient, squamous cell carcinoma in the transplanted kidney in one patient, malignant schwannoma in one patient, and Epstein-Barr virus-related lymphoma in two patients. The mortality rate was 0.79 per 1000 person-years (95% confidence interval 0.38, 1.85). Conclusions: Early diagnosis and treatment of malignancies in transplant recipients is an important challenge. Therefore, enhanced surveillance and continued vigilance for malignancy following KT are necessary. [ABSTRACT FROM AUTHOR]

Backgrounds: Recent studies have reported increased risks of adverse events from systemic corticosteroids even with only low-dose or short-term use. Some patients with asthma experience complications requiring systemic corticosteroids. However, few studies have examined issues associated with administration of systemic corticosteroids for reasons other than asthma among subjects with asthma. Objectives: We investigated patterns of systemic corticosteroid exposure for reasons other than asthma in subjects with asthma. Method: We retrospectively reviewed the records of adult subjects with asthma followed up for >1 year at Yokohama City University Hospital from January 1, 2010, to December 31, 2019. We investigated patterns and reasons for systemic corticosteroid use during follow-up. In addition, factors related to systemic corticosteroid use for reasons likely other than asthma were investigated. Results: Among the 568 subjects with asthma analyzed, 326 (57.4%) had received systemic corticosteroids for some reason. Among those 326 patients, 120 (36.8%) had received systemic corticosteroids for reasons likely other than asthma. Multivariable analysis revealed rheumatoid arthritis, eosinophilic granulomatosis with polyangiitis, other collagen vascular diseases, chronic rhinosinusitis, and malignancy as positively associated with systemic corticosteroid exposure for reasons likely other than asthma in subjects with asthma. Conclusions: About 40% of systemic corticosteroid use in subjects with asthma was for reasons likely other than asthma. Clinicians should be aware of their asthma patients' exposures to systemic corticosteroids for nonasthma reasons, to avoid missing adverse events or underestimating the severity of asthma, and to reduce systemic corticosteroid use. [ABSTRACT FROM AUTHOR]

Summary: Anemia and vitamin D deficiency are associated with allograft failure, and hence, are potential therapeutic targets among kidney transplant recipients (KTRs). We conducted a multicenter, two‐by‐two factorial, open‐label, randomized clinical trial to examine the effects of anemia correction and vitamin D supplementation on 2‐year change in eGFR among KTRs (CANDLE‐KIT). We enrolled 153 patients with anemia and >1‐year history of transplantation across 23 facilities in Japan, and randomly assigned them to either a high or low hemoglobin target (>12.5 vs. <10.5 g/dl) and to either cholecalciferol 1000 IU/day or control. This trial was terminated early based on the planned interim intention‐to‐treat analyses (α = 0.034). Among 125 patients who completed the study, 2‐year decline in eGFR was smaller in the high vs. low hemoglobin group (i.e., −1.6 ± 4.5 vs. −4.0 ± 6.9 ml/min/1.73 m2; P = 0.021), but did not differ between the cholecalciferol and control groups. These findings were supported by the fully adjusted mixed effects model evaluating the rate of eGFR decline among all 153 participants. There were no significant between‐group differences in all‐cause death or the renal composite outcome in either arm. In conclusion, aggressive anemia correction showed a potential to preserve allograft kidney function. [ABSTRACT FROM AUTHOR]

Objective: We reviewed malignancy related maternal deaths in Japan to ascertain if there were avoidable factors.Methods: Malignancy-related maternal death in Japan reported to the Maternal Death Exploratory Committee, from 2010 to 2016 inclusive.Results: There were 12 cases of maternal death caused by malignancy. There were four gastric cancers (two poorly differentiated adenocarcinoma, one signet ring cell carcinoma with adenocarcinoma, one histology not available), 3 leukemia (two acute myeloid leukemia, one aggressive NK cell leukemia), two ureteral cancers (histology not available), one malignant lymphoma (diffuse large B-cell lymphoma with translocation), one brain tumor (gliomatosis cerebri), and one cervical cancer (glassy cell carcinoma). Two gastric cancer patients had chronic gastric pain before conception. In two cases the physicians commented that they had avoided computed tomography and the brain biopsy needed for diagnosis because the patient was pregnant. At diagnosis, the clinical stages were II-IV in 9, and the performance status was 3-5 in 8. Indication for delivery was exacerbated maternal condition in 5, for treatment in 3, spontaneous labor in 3, and one patient declined elective delivery. Median [interquartile rage] (range) gestational weeks of delivery was 29 [24-30] (19-40). One cervical cancer patient had a radical hysterectomy and chemotherapy for 10 months. However, three leukemia and one gastric cancer patients had chemotherapy within 10 d because they deteriorated rapidly. Another seven cases did not have any treatment because of poor general condition or because they remained undiagnosed. In all cases, the Committee considered that there was no evidence of substandard care.Conclusion: In these cases, both the clinical stages and biological degree of malignancy were high. In two-thirds of cases, early termination of the pregnancy was indicated because of deteriorating maternal condition. Chemotherapy was not effective because of short available time for therapy and the advanced stage of the cancers when diagnosed. Encouraging women to have a thorough medical assessment before conception, and early diagnosis and treatment before pregnancy, appears to be the only practical way to reduce deaths from malignancy while a woman is pregnant. [ABSTRACT FROM AUTHOR]

Objective: Tracheal reconstruction is a rare surgical procedure and the actual incidence of or indications for this procedure have not been thoroughly elucidated. We performed the nationwide database analysis to clarify the real-world situation of laryngotracheal surgery requiring cervical tracheal reconstruction.Methods: Patients who underwent surgical treatment for laryngotracheal stenosis or defect from 2008 to 2016 were identified from the Diagnosis Procedure Combination inpatient database, collected from 270 acute care hospitals in Japan. Patients were divided into two groups based on presence/absence of malignancy, and T-tube or tracheotomy dependence at 6 months after surgery was compared between the two groups.Results: One hundred and thirty-four patients (75 males) were identified. The median age at surgery was 65.5 years. The most common indication for surgery was malignancy (n = 60, 44.8%), followed by iatrogenic (n = 25, 18.6%), trauma (n = 6, 4.5%), malformation of the larynx and trachea (n = 6, 4.5%), and chronic inflammatory disease (n = 4, 2.8%). Thyroid cancer was the most common malignancy (n = 38). Thirty patients (22.4%) failed to decannulate within 6 months and malignancy was associated with a lower dependence on T-tube or tracheotomy at 6 months after surgery (adjusted odds ratio: 0.25, 95% confidence interval: 0.08-0.79).Conclusion: A Japanese health insurance claims database provided a useful overview of the clinical features and outcomes of patients who underwent cervical tracheal reconstruction surgery for laryngotracheal stenosis or defect. [ABSTRACT FROM AUTHOR]

Summary: Purpose Anorexia induced by cytotoxic chemotherapy on delayed phase is a highly frequent adverse event. We aimed to determine the effects of rikkunshito (RKT) on chemotherapy-induced anorexia (CIA) in patients with lung cancer. Methods This prospective, randomized, cross-over pilot trial included 40 lung cancer patients scheduled to undergo cisplatin-based chemotherapy and randomized to either a group given RKT 7.5 g/day for 14 days (Group A, N = 20) or not (Group B, N = 20), then the treatments were switched. All patients received dexamethasone, palonosetron hydrochloride and aprepitant regardless of group assignment. Rescue drugs were allowed as required. The primary and key secondary endpoints were changes in caloric intake and in plasma acylated ghrelin (AG) levels, respectively. Average daily caloric intake during days 3 to 5 was compared with that on day 1 of each course. Results The primary and key secondary endpoints were analyzed in 31 patients (per protocol population) completing the study. Reduction rate of caloric intake was lower in RKT, than in control courses (18% vs. 25%, P = 0.025). Plasma AG levels significantly declined between days 1 and 3 in RKT (12.3 vs. 7.5 fmol/mL, P < 0.001) and control (10.8 vs. 8.6 fmol/mL, P < 0.001) courses. However, those obviously increased to 8.5 fmol/mL (P = 0.025) by day 5 in RKT course but not in control course (7.7 fmol/mL, P = 0.28). Conclusions Rikkunshito could mitigate CIA and ameliorate plasma AG levels during the delayed phase of CDDP-based chemotherapy in lung cancer patients. Clinical trial registration numbers: UMIN000010748. [ABSTRACT FROM AUTHOR]

The objective of this study was to identify factors predictive of malignancy in patients with polymyositis (PM) and dermatomyositis (DM) in Japan. We conducted a retrospective study of PM and DM patients who were admitted to our hospital between January 1992 and September 2017. Among 134 patients, 29 (21.6%) were diagnosed with cancer in the 3 years prior to and 3 years after the initial diagnosis of PM or DM. According to multivariate analyses, male sex [odds ratio (OR) = 3.65, p = 0.03], old age (OR = 1.05, p = 0.02), and a past history of diabetes mellitus (OR = 10.4, p = 0.005) were associated with an increased risk of malignancy. The absence of interstitial lung disease (ILD) (OR = 0.25, p = 0.03) was also associated with an increased risk of malignancy. Diabetes mellitus was observed in 28.6% of PM and DM patients with malignancy, but in only 7.3% of those with malignancy. Survival was significantly lower in patients with malignancy than in those without malignancy (p < 0.001). Independent factors associated with malignancies in patients with PM or DM were male sex, old age, the absence of ILD, and, especially, a past history of diabetes mellitus. [ABSTRACT FROM AUTHOR]

Background: The background status and the current treatment options of patients with rheumatoid arthritis (RA) who develop malignant lymphoma (ML) and other malignancies are unclear. This study investigated the differences in background factors between ML and other malignancies that occur in RA patients and post-malignancy treatment., Methods: We identified 935 RA patients with new-onset malignancies among 110,571 person-years registered in the National Database of Rheumatic Disease in Japan from 2012 to 2018. Analysis cohorts 1 and 2 included 597 and 490 patients with available data for 1 year before and after the development of malignancies, respectively. Factors associated with the development of ML were longitudinally evaluated by multiple logistic regression analyses., Results: Of the 935 patients (mean age 70.5, standard deviation 9.9), 15.5% had ML; this was comparable to the rate of lung cancer (14.3%). In cohort 1, methotrexate (MTX), biological disease-modifying anti-rheumatic drugs (bDMARDs), and non-steroidal anti-inflammatory drugs (NSAIDs) were used in 74.4%, 23.4%, and 56.7% of ML and in 56.8%, 25.4%, and 35.3% of other malignancies 1 year before the occurrence of malignancies. Clinical disease activity index (CDAI) and C-reactive protein were similar between the two groups. Multivariable analysis showed that MTX use (odds ratio [OR]: 2.22, 95% CI [confidence interval]: 1.32-3.73, p=0.003) and NSAID use (OR: 2.51, 95% CI: 1.58-3.98, p <0.001) were significantly associated with the development of ML versus other malignancies. However, this association was not observed with bDMARDs. In cohort 2, one year after the development of malignancies, MTX was used in none of ML and 41.8% of patients who developed other malignancies. In both malignancy groups, approximately 15% of patients received bDMARDs and 50% received glucocorticoids. IL-6 inhibitors were preferentially prescribed in patients with ML versus those with other malignancies. At year 1, CDAI remission was achieved in 37.3% and 31.1% of patients in the ML and other malignancy groups, respectively., Conclusion: Patients receiving long-term treatment with MTX and NSAIDs may be at a relatively high risk of developing ML. The treatment landscape after developing malignancies differed considerably between patients with ML and other malignancies, and different treatment strategies should be established., Competing Interests: Declaration of Competing Interest TS has received research grants and/or honoraria from Abbvie Japan Co., Ltd., AsahiKASEI Co., Ltd., Astellas Pharma Inc., Ayumi Pharmaceutical, Bristol Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo., Eli Lilly Japan K.K., Mitsubishi-Tanabe Pharma Co., Ono Pharmaceutical, Pfizer Japan Inc., Takeda Pharmaceutical Co. Ltd., and UCB Japan Co. Ltd. TM has received grants and/or honoraria from Abbvie Japan Co., Ltd., AsahiKASEI Co., Ltd., Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo., Eli Lilly Japan K.K., Mitsubishi-Tanabe Pharma Co., Ono Pharmaceutical, Pfizer Japan Inc., Takeda Pharmaceutical Co. Ltd., Taisho Pharmaceutical Co. Ltd., and UCB Japan Co. Ltd. YU has received honoraria from AsahiKASEI Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Gilead Sciences, Inc., Pfizer Japan Inc., and Sanofi K.K. KK has received grants and/or honoraria from Abbvie Japan Co., Ltd., AsahiKASEI Co., Ltd., Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Mitsubishi-Tanabe Pharma Co., Ayumi Pharmaceutical, Bristol Myers Squibb K.K., Taisho Pharmaceutical Co. Ltd., and UCB Japan Co. Ltd, Pfizer Japan Inc., Eisai Co., Ltd., and Gilead Sciences, Inc. All other authors have declared no conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)

Retroperitoneal fibrosis (RPF) is a rare cause of hydronephrosis and progressive renal dysfunction with unidentified origin. RPF is categorized into idiopathic RPF with/without immunoglobulin G4 (IgG4)-related disease (IgG4-RD), and secondary RPF. Identifying the underlying cause is challenging and often associated with delayed diagnosis or therapeutic interventions. We investigated RPF's clinical characteristics based on different etiologies and factors that may help distinguish the underlying causes. We analyzed the cases of 49 patients with RPF that was radiographically diagnosed at our institution (2008-2022). The cohort was 77.6% males; 75.5% had idiopathic RPF and 24.5% had secondary RPF. Among the idiopathic patients, 54.1% had IgG4-RD. The patients were likely to have abdominal pain, lower back pain/lumbago, and constitutional symptoms including generalized fatigue and fever. The idiopathic patients were likely to have higher serum IgG4 and IgG levels and lower serum C3 levels compared to secondary RPF. The IgG4-RPF patients were likely to have higher serum IgG4 levels and lower serum C-reactive protein, ferritin, and C3 levels compared to the idiopathic RPF patients without IgG4-RD. These findings might reflect underlying systemic inflammatory responses. Comprehensive laboratory testing, including serum inflammatory markers and immunological panels, is recommended for radiologically diagnosed RPF patients., Competing Interests: No potential conflict of interest relevant to this article was reported.

Purpose: Lung transplant recipients are known to be at risk of a postoperative malignancy. In Western countries, skin cancer and post-transplant lymphoproliferative disorder (PTLD) are the most common malignancies in this cohort. We conducted this study to evaluate the characteristics of postoperative malignancies in Japanese patients following living-donor lobar lung transplantation (LDLLT) or cadaveric lung transplantation (CLT). Methods: We reviewed the medical records of 120 Japanese patients who underwent either LDLLT ( n = 62) or CLT ( n = 58) between April 2002 and July 2015. Results: Postoperative malignancy developed in 11 patients (9.2 %), as PTLD in 7, breast cancer in 1, gastric cancer in 1, glioblastoma in 1, and adenocarcinoma of unknown primary in 1. Twenty-six (21.7 %) of the 120 transplant patients had a history of malignancy pre-transplant; however, the postoperative malignancies were all de novo without any recurrence of the original disease. The malignancies developed after LDLLT in six patients (9.7 %) and after CLT in 5 patients (8.6 %). Three of the four patients with solid organ malignancies had distant metastasis at diagnosis. Three patients died of PTLD and one patient died of gastric cancer. Conclusions: PTLD occurred after both LDLLT and CLT. There was no case of skin cancer in this series of Japanese patients, suggesting ethnic differences. Solid organ malignancies in lung transplant recipients tended to progress rapidly. [ABSTRACT FROM AUTHOR]

Objectives: To investigate and compare the risk for malignancy in rheumatoid arthritis (RA) patients treated with biologics in Japan to the general population. Methods: Data for 14,440 patients from 335 institutions who were given infliximab, etanercept, adalimumab, golimumab, tocilizumab, or abatacept were retrieved from the SafEty of biologics in Clinical Use in Japanese patients with RhEumatoid arthritis (SECURE) database. Results: We identified 333 incidents of malignancies in 320 patients during 49,320 patient-years (PY). The age- and sex-standardized incidence rate (ASR) (95% confidence interval [CI]) for overall malignancy of the SECURE cohort was 313.9/105 PY (271.4-361.3), and the standardized incidence rate ratio (SIR) (95% CI) was 0.745 (0.667-0.826). The ASR was decreased compared to the estimated incidence rate of malignancies in the Japanese general population (462.4/105 PY). The SIRs for site-specific nonhematopoietic malignancies of the SECURE cohort were not significantly elevated compared to the Japanese general population. A significant increase of SIR for malignant lymphoma (6.183, 95% CI, 4.809-7.643) was found in the SECURE cohort, similar to or slightly higher than the SIR previously reported from Japanese cohorts for RA patients. Conclusions: Continued vigilance with larger numbers of patients, longer observation periods, and inclusion of different biologics are recommended. [ABSTRACT FROM AUTHOR]

Little is known about the risk factors for long-term poor outcome in pediatric renal transplantation. Between 1973 and 2010, 111 renal transplants (92 living donations) were performed in 104 children (56 males, mean age, 12.5 yr) at the Social Insurance Chukyo Hospital, and followed-up for a mean period of 13.6 yr. The patient survival at 1, 5, 10, 15, 20 (living- and deceased-donor transplants), and 30 yr (living-donor transplants only) was 98.1%, 92.8%, 87.8%, 84.9%, 82.6%, and 79.3%. The graft survival at 1, 5, 10, 15, 20, and 30 yr was 92.0%, 77.3%, 58.4%, 50.8%, 38.5%, and 33.3%. The most common cause of graft loss was CAI, AR, death with functioning, recurrent primary disease, ATN, and malignancy. Donor gender, ATN, malignancy/cardiovascular events, and eras affected patient survival. AR and CAI were the risk factors for graft loss. The evolved immunosuppression protocols improved the outcome by reducing AR episodes and ATN but not CAI, suggesting CAI as the major risk factor for graft loss. CAI was correlated with AR episodes, CMV infection, and post-transplant hypertension. Strategies for preventing the risk factors for malignancy/cardiovascular events and CAI, including hypertension/infection, are crucial for better outcomes. [ABSTRACT FROM AUTHOR]

Background: Physician attire influences perceptions of care. This study was conducted to evaluate the impact of physician attire on perceptions of care by patients and families in a Japanese palliative care unit., Methods: From November 2018 to February 2020, patients and family members admitted to the Palliative Care Unit at Jichi Medical University Hospital were recruited and completed a survey consisting of 4 demographic questions and 15 questions regarding perceptions of care. A 7-point Likert scale (1 = strongly agree, 4 = neutral, 7 = strongly disagree) was used to judge attire (name tag, long sleeve white coat, short sleeve white coat, scrubs, scrub color, jeans, sneakers) addressing patient and overall impact on perception of care., Results: Of 203 patients admitted, 79 were enrolled. Surveys were received from 23 patients and 52 family members. Patients and families want physicians to wear name tags (median, interquartile range) (2, 1-2) and white coats (3, 2-4). Patients want to be addressed by surnames (2, 1.5-4). Patients and family members have neutral opinions about short sleeve white coats (4, 4-4) and scrubs (4, 4-4). Jeans were not liked (4, 4-6) while sneakers are acceptable (3, 2-4). The impact of attire on perceptions of care is significantly (p = .04) greater for patients (3, 2-4) than family members (4, 3-4)., Conclusion: Patients and family members prefer their physicians to wear name tags and white coats and address patients by surnames. Physician attire has a significantly greater impact on perceptions of care for patients than family members in a palliative care unit.

The article presents a case study of a 12-year-old neutered male Japanese domestic cat admitted to the veterinary hospital due to coughing, dysorexia, diarrhea and vomiting. The cat died after a month of its first visit to the hospital and researchers did an autopsy to determine the cause of his death. Moreover, results of ultrasonography revealed that the cat had malignant and metastasizing cardiac ganglioneuroma.

To determine the incidence of malignancy and site-specific malignancies in Japanese patients with rheumatoid arthritis (RA). In a prospective large observational cohort study named IORRA, 7,566 patients with RA were enrolled from April 2001 to April 2005 and were followed up to October 2005. Occurrence of malignancy was originally collected by patient reports of IORRA survey biannually from April 2001 to October 2005, and was confirmed by medical records. Standardized incidence rate (SIR) of the observed-to-expected cancer incidence and 95% confidence intervals (95% CI) were then calculated. Factors obtained at first enrollment in IORRA were assessed for association with risk of malignancy using the Cox proportional hazards model. A total of 177 malignancies in 173 patients (58 in men, 115 in women) were identified during the observation period of 25,567 person-years. The age- and sex-standardized incidence rate of malignancy was 437.1 (men, 706.8; women, 366.1) per 100,000 person-years. The SIR of malignancy was slightly excess (SIR 1.18, [95% CI 1.02-1.37]) in all patients, but 1.29 (95% CI 0.99-1.67) in men, and 1.13 (95% CI 0.94-1.36) in women. A significant excess of lymphoma (SIR 6.07, [95% CI 3.71-9.37]) and lung cancer (SIR 2.29, [95% CI 1.57-3.21]), whereas decreased incidence of colorectal cancer (SIR 0.49, [95% CI 0.26-0.83]), were found. Male gender and older age were identified as risk factors for malignancy. A slight excess in the incidence of overall malignancy and highly excess of lymphoma in Japanese RA patients was demonstrated. [ABSTRACT FROM AUTHOR]

We report six cases of autoimmune acquired coagulation factor VIII deficiency, which is a rare bleeding disorder. It is an autoimmune disease, however, there are various causes. We experienced cases with malignancy, co-exist with another autoimmune disease, pregnancy, and unknown epidemiology with repeated bleeding episode. All patients were controlled the acute bleeding phase and they have been under treatment with immunosuppression. [ABSTRACT FROM AUTHOR]

Anti-laminin 332 mucous membrane pemphigoid (MMP) is an autoimmune blistering disease characterized by predominant mucosal lesions and autoantibodies against laminin 332. The exact diagnosis of anti-laminin 332 MMP is important since nearly 30% of patients develop solid cancers. This study compared two independently developed diagnostic indirect immunofluorescence (IF) tests based on recombinant laminin 332 expressed in HEK239 cells (biochip mosaic assay) and the migration trails of cultured keratinocytes rich in laminin 332 (footprint assay). The sera of 54 anti-laminin 332 MMP, 35 non-anti-laminin 332 MMP, and 30 pemphigus vulgaris patients as well as 20 healthy blood donors were analyzed blindly and independently. Fifty-two of 54 and 54/54 anti-laminin 332 MMP sera were positive in the biochip mosaic and the footprint assay, respectively. In the 35 non-anti-laminin 332 MMP sera, 3 were positive in both tests and 4 others showed weak reactivity in the footprint assay. In conclusion, both assays are easy to perform, highly sensitive, and specific, which will further facilitate the diagnosis of anti-laminin 332 MMP., Competing Interests: DZ and ES have obtained grants from Euroimmun, Lübeck, for research and development projects. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Goletz, Giurdanella, Holtsche, Nijenhuis, Horvath, Diercks, Zillikens, Hashimoto, Schmidt and Pas.)

Background: We evaluated malignancy according to the characteristics of pericardial fluid in symptomatic Japanese patients undergoing pericardiocentesis and computed tomography (CT)., Methods: This was a retrospective, single-center, observational study of 125 symptomatic patients undergoing pericardiocentesis. The patients were classified into two groups: a malignancy group and a non-malignancy group, according to the primary disease and cytology of the pericardial effusion (PE). We compared the pericardial fluid sample and CT measurements between both groups., Results: All patients were diagnosed as having exudative PE by Light's criteria. PE with malignant cells was demonstrated in 76.8% of the malignancy group patients. Pericardial to serum lactate dehydrogenase (LDH) ratio > 0.6, as one of Light's criteria, was associated with malignancy (p = 0.017). Lower serum brain natriuretic peptide (BNP) concentration was also associated with malignancy (BNP: 126.9 ± 89.8 pg/ml vs 409.2 ± 97.7 pg/ml, malignancy vs non-malignancy groups, respectively; p = 0.037). A significant difference was observed in pericardial fluid glucose level between the malignancy and non-malignancy groups (pericardial fluid glucose: 78.24 ± 48.29 mg/dl vs 98.41 ± 44.85, respectively; p = 0.048). Moreover, CT attenuation values (Hounsfield units (HU)) tended to be higher in the malignancy group vs the non-malignancy group (22.7 [interquartile range (IQR), 17.4-26.0] vs 17.4 [IQR, 13.7-26.4], respectively; p = 0.08). The sensitivity and specificity of pericardial fluid glucose level ≤ 70 mg/dl and CT attenuation values > 20 HU were 40.9% and 89.6%, respectively, in the malignancy group. The positive- and negative predictive values of pericardial fluid glucose level ≤ 70 mg/dl and CT attenuation values > 20 HU were 85.7% and 50.0%, respectively, in the malignancy group. Pericardial fluid glucose level ≤ 70 mg/dl and CT attenuation values > 20 HU were cutoff values associated with malignancy (p = 0.012)., Conclusions: Lower pericardial fluid glucose level with higher CT attenuation values may suggest malignancy-related PE.

The aim of the study was to investigate the incidence of and risk factors for de novo malignancy after heart transplantation (HTx) in a single center. We assessed 102 consecutive patients who received HTx and were followed-up in our center regularly for > 1 year from June 2006 to May 2018. We investigated the incidence of and risk factors for de novo malignancy. The cumulative incidence of each malignancy type during the follow-up period was one (0.98%) for skin cancer, four (3.92%) for nonskin solid organ cancer, and six (5.88%) for posttransplant lymphoproliferative disorder (PTLD). The percentage of patients with more than one infectious event ≤ 1 year after HTx was higher in the malignancy group than in the non-malignancy group. Furthermore, Kaplan-Meier analysis revealed that the incidence rate of infectious events was higher in patients with malignancies than in those without (log-rank P < 0.001). After dividing malignancies into a PTLD group and a solid organ malignancy group, we found that negative Epstein-Barr virus serostatus, cytomegalovirus-positive antigenemia, and the occurrence of any viral or gastrointestinal infectious event at ≤ 1 year were more frequent in patients with PTLD than in patients without it. The survival rate was significantly lower for patients with solid organ malignancy than for patients without malignancy. In conclusion, there was a correlation between infectious events and de novo malignancy, particularly in patients with PTLD. We should confirm this finding by conducting a larger cohort study.

Background: Glycemic variability has been suggested to be related to some unfavorable outcomes, but malignancy development has not been evaluated. The aim of this study was to evaluate the association of glycemic variability with malignancy development among the population without diabetes.Methods: We conducted a retrospective cohort study at a large teaching hospital in Tokyo, Japan, from 2005 to 2016. We included all participants without diabetes who underwent voluntary health check-ups. Our outcome was the development of any malignancy. As a measure of glycemic variability, we calculated the quotient of CV in HbA1c and categorized subjects into quartile groups. A Cox proportional hazard model was applied, adjusting for patient demographics and social and family histories.Results: A total of 42,731 participants were included in this study; the mean age was 53.8 and 48.3% were male. During the median follow up of 2639 (interquartile range (IQR):1787-3662) days, 2435 participants (5.7%) developed malignancies. Participants who had larger glycemic variability (CV in HbA1c; hazard ratio (HR) 1.15, 95%confidence interval (CI):1.02-0.31 for the second quartile group; HR 2.20, 95%CI:1.95-2.48 for the third quartile group, HR 4.66, 95%CI:4.16-5.21 for the fourth quartile group, compared to first quartile group) had a significantly higher risk of malignancies.Conclusion: We found an association between large glycemic variability and a high risk of future malignancies in a dose-dependent manner among people without diabetes. This finding suggests that maintaining a constant level of glucose may have favorable effects on cancer prevention in people without diabetes. [ABSTRACT FROM AUTHOR]

Study Objectives: Continuous positive airway pressure (CPAP) improves quality of life in patients with obstructive sleep apneas. However, the long-term benefit in all-cause mortality and cardiovascular death are limited among Japanese., Methods: We conducted a retrospective study of patients treated in our sleep clinic in Okinawa, Japan. All patients with full-scale polysomnography from September 1990 to December 2010 were investigated in terms of outcomes such as death (dates and causes of death) between 2012 and 2013 by chart review, telephone calls, and letters of inquiry. Propensity-score matching was performed to balance baseline characteristic differences between a CPAP user group and a nonuser group. The primary outcomes were all-cause mortality and a composite of cardiovascular disease mortality, such as heart disease and stroke, between the two groups., Results: The CPAP user group, almost double in number, had more severe obstructive sleep apnea, more comorbidities, smoking, and alcohol consumption compared to the nonuser group but no significant difference in Epworth Sleepiness Scale. Propensity-score matching selected 1,274 of 4,519 patients as the CPAP user group and 1,274 of 2,128 as the CPAP nonuser group. Mean age of the patients was 52.3 (±13.5) years and 79% were men. After a median follow-up of 79 (interquartile interval, 24 to 128) months in the CPAP user group and 73.5 (interquartile interval, 26 to 111) in the non-CPAP group, death from all causes occurred in 53 (4.2%) patients in CPAP user group and in 94 (7.4%) patients in CPAP nonuser group. The leading cause of death was malignancy in each group. The hazard ratios for all-cause mortality and cardiovascular disease deaths were 0.56 (95% confidence interval (CI), 0.41-0.78) and 0.54 (95% CI, 0.28-1.03) between CPAP user group and CPAP nonuser group, respectively., Conclusions: In obstructive sleep apnea patients, CPAP use was associated with lower all-cause mortality., (© 2021 American Academy of Sleep Medicine.)

Objective Recent studies suggest a significant association between sarcoidosis and malignancy, although the results have remained controversial. The aim of this study is to evaluate the clinical features of patients with sarcoidosis associated with malignant diseases in Japan. Patients We conducted a medical record review of all sarcoidosis patients in Tohoku University Hospital between January 1, 1981, and May 31, 2017. Methods The clinical records and pathology reports for each patient were screened, and the clinical characteristics of malignancies as well as sarcoidosis were reviewed. Results A total of 52 (18.8%) patients with malignancy were identified among 277 patients with sarcoidosis. Among those 52 patients, we identified 62 with malignant diseases. These patients were older and more likely to be women than the remaining 225 (81.2%) sarcoidosis patients without malignancy. The most prevalent malignant disease was breast cancer (14 cases, 22.6%), followed by stomach cancer (8 cases, 12.9%) and lung cancer (7 cases, 11.3%). Among the 14 patients with both sarcoidosis and breast cancer, 8 (57.1%) were diagnosed with breast cancer before sarcoidosis. All of these eight cases had undergone surgical resection of the cancer. Conclusion This study showed a higher incidence of patients with both sarcoidosis and malignancy in Japan than in some western countries. Breast cancer is the most prevalent malignant disease. The high frequency of sarcoidosis after surgical resection of breast cancer may suggest a causative association between malignancy and the development of sarcoidosis.

Background: Self-expandable metal stents (SEMSs) are widely used in patients with distal malignant biliary obstruction. A SEMS that can avoid occlusion as much as possible is desirable., Aims: The aim of this multicenter single-arm prospective study was to assess the clinical effectiveness and safety of a novel fully covered braided SEMS., Methods: We enrolled consecutive patients with distal malignant biliary obstruction between February 2016 and November 2017 at ten tertiary-care medical centers., Results: We included 79 patients with a median age of 76 years; 47 (59.5%) patients were men. The technical and clinical success rate was 98.7% and 93.6%, respectively. Recurrent biliary obstruction occurred in 14 patients (17.9%); stent ingrowth, overgrowth, migration, and other occurred in five (6.4%), four (5.1%), four (5.1%), and one (1.3%) patients, respectively. All reinterventions in patients with recurrent biliary obstruction were successful via the transpapillary approach. Adverse events occurred in 15 patients (19.2%); cholangitis, pancreatitis, and others occurred in ten (12.8%), three (3.8%), and two (2.6%) patients, respectively. The stent patency probability at 6 months was 48.5%. Median time to stent patency was 171 days, median time to recurrent biliary obstruction was 536 days, and median survival time was 195 days., Conclusions: We confirmed the utility and safety of a novel fully covered braided SEMS with low axial force and high radial force in patients with malignance biliary obstruction. This novel SEMS is recommended in patients with distal malignant biliary obstruction.

Dermatomyositis (DM) is an autoimmune inflammatory disease characterized by skin eruptions and myositis. Anti-transcriptional intermediary factor 1-γ antibody (anti-TIF1-γ Ab) is one of the most frequently detected myositis-specific autoantibodies and adults positive for anti-TIF1-γ have markedly higher rates of malignancy. Our aim was to determine the clinical associations of anti-TIF1-γ levels in 31 Japanese adult DM patients positive for anti-TIF1-γ. We determined associations between the anti-TIF1-γ index and patient characteristics and disease severities. Sixteen patients with anti-TIF1-γ Ab had concomitant malignancies. A mild positive correlation was found between the levels of serum creatine phosphokinase at the first visit and anti-TIF1-γ levels. In contrast, there was no significant difference in the anti-TIF1-γ Ab index between patients with and without malignancy. Dysphagia tended to be observed in patients with malignancy. On sequential analysis, anti-TIF1-γ levels in patients without malignancy were lower or turned negative after treatment for DM. Ab titers tended to be sustained in patients with stage IV malignancies. Interestingly, a re-increase in the Ab titer was observed on recurrence of malignancy or increase in DM activity. Four patients were completely cured of their malignancies, and anti-TIF1-γ levels in three patients turned negative with the loss of DM activity. These data suggest that higher anti-TIF1-γ titers may not directly indicate the presence of malignancy. Nevertheless, longitudinal changes in the anti-TIF1-γ index in individual patients may partially reflect activities of both DM and malignancy., (© 2020 Japanese Dermatological Association.)

Aims: Endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is performed safely and effectively in elderly patients; however, whether ESD for EGC in elderly patients with frailty is safe and improves prognosis remains unclear., Methods: In total, 142 patients aged ≥80 years who underwent ESD for EGC between September 2008 and September 2014 were included. We compared outcomes between patients with frailty and those without frailty. Frailty was assessed using the Clinical Frailty Scale (CFS) based on a patient's status before admission. Study endpoints were short- and long-term clinical outcomes after ESD., Results: Patients were allocated into two groups: no frailty (CFS 1-3, n = 101) versus frailty (CFS 4-7, n = 41). Short-term clinical outcomes, specifically, adverse events and curability, did not differ between the two groups. For the long-term clinical outcomes, patients with frailty had significantly worse outcomes after ESD than those without frailty (the 3-year overall survival rates were 73.2% vs. 93.1%; P < 0.001 with log-rank test). The Cox proportional hazards model showed that frailty was only an independent risk factor for poor prognosis., Conclusions: ESD for EGC is safe for elderly patients with or without frailty. However, elderly patients with frailty have a significantly poorer prognosis than those without frailty after ESD. Our results indicate that the frailty evaluation may be helpful to determine whether ESD for EGC should be performed. Geriatr Gerontol Int 2020; 20: 461-466., (© 2020 Japan Geriatrics Society.)

The HOTAIR gene encodes a long noncoding RNA (lncRNA), which functions in development and tumorigenesis. A single nucleotide polymorphism (SNP) rs920778 in the HOTAIR gene, has been recurrently studied for susceptibility to many cancers including oesophageal cancer, gastric cancer, lung cancer, and hepatocellular carcinoma. Most of these studies were conducted in Chinese populations, and a few in Turkish, Iranian, and Portuguese populations. They mostly give rise to controversial results. It still remains largely unknown whether the cancer risk is conferred in a Japanese population. Here, we established an association study on the representative SNP rs920778, to examine its contribution to the presence of cancer in consecutive autopsy cases in the JG-SNP database. A total of 1373 subjects (mean age 80) including 827 cancer positive and 546 cancer negative subjects were analyzed. As a result, the occurrence of overall cancer was not associated with the rs920778 polymorphism (p > 0.05). For each cancer type, we did not find association except for lung cancer (p = 0.04) which was more likely a by-chance association after multiple testing. Our findings imply that rs920778 polymorphism does not affect total cancer presence and the effect on specific cancer types is also weak in the Japanese population., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) was developed with the aim of further improving the diagnostic performance of endoscopic ultrasound. Although novel puncture needles have been specifically designed for collecting sufficient tissue specimens, clinical studies have indicated no clear difference in diagnostic performance between these novel needles and conventional puncture needles. Recently, a needle with Franseen geometry was developed specifically for EUS-FNA biopsy. Due to the characteristic shape of its tip, the Franseen needle is expected to be effective for scraping tissues, thus potentially increasing the diagnostic accuracy of EUS-FNA biopsy. We plan to carry out a prospective, multicenter, open-labeled, controlled trial to compare conventional and Franseen needles in terms of the diagnostic accuracy of EUS-FNA for evaluating the malignancy of pancreatic mass lesions., Methods/design: The study will enroll 520 patients with pancreatic mass managed at any of 21 participating endoscopic centers. Lesion samples obtained using 22G conventional and Franseen needles will be assessed to compare the efficacy and safety of these two types of needles in EUS-FNA for evaluating the malignancy of mass lesions in the pancreas. Tissue samples will be fixed in formalin and processed for histologic evaluation. For the purpose of this study, only samples obtained with the first needle pass will be used for comparing the: (i) accuracy of the malignancy diagnosis, (ii) sensitivity and specificity for the malignancy diagnosis, (iii) procedure completion rate, (iv) sample cellularity, and (v) incidence of complications. Patient enrollment begins on July 17, 2018., Discussion: The outcomes of this study may provide insight into the optimal needle choice for evaluating the malignancy of pancreatic solid lesions, thus aiding in the development of practice guidelines for pancreatic diseases., Trial Registration: University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR), UMIN000030634. Registered on 29 December 2017. http://www.umin.ac.jp/ Version number: 01.2017.12.28.

Background: Acute kidney injury (AKI) is associated with higher mortality and cardiovascular events. However, association between AKI and non-cardiac events such as infection or malignancy is largely unknown., Methods: This is a retrospective cohort study. Inclusion criteria were adults who underwent non-cardiac surgery from 2007 to 2011 at Nara Medical University Hospital. Exclusion criteria were urological surgery, obstetric surgery, missing creatinine values peri-operatively, and pre-operative dialysis. The end of observation period was at the end of 2015 or loss to follow-up. A predictor was AKI defined by KDIGO criteria within 1-week post-operatively. Outcomes were hospitalization for infection or diagnoses of malignancy. Associations between AKI and outcomes were examined by Cox regression models., Results: Among 6692 subjects, 445 (6.6%) developed AKI. During median follow-up of 4.0 years, there were 485 hospitalizations for infection and 1138 diagnoses of malignancy (2.0 and 5.1 events/100 patient-years, respectively). After adjustment for potential confounders, AKI was independently associated with hospitalization for infection and diagnoses of malignancy (Hazard ratio [95% confidence interval]: 1.64 [1.23-2.20] and 1.31 [1.06-1.61], respectively). Excluding recurrence of malignancy from outcomes and analyses limited to those who recover renal function by the time of discharge yielded similar results. Absolute lymphocyte counts were significantly lower and neutrophil-to-lymphocyte ratios were significantly higher among those with AKI., Conclusions: AKI was significantly associated with hospitalization for infection and development of malignancy during long-term follow-up. Those with AKI might be in persistent immunosuppressed state.

Resolution of regional disparities in cancer mortality is global challenge. Establishing an equal system of cancer treatment throughout the country is required under the Cancer Control Act in Japan. The types of treated cancer may reflect practical experience at the institutions and cooperation to other institutions. This study investigated the types treated at the institutions in rural communities of Japan. A questionnaire survey was conducted for 811 public rural institutions (clinics and small-to-middle-sized hospitals [< 200 beds]) in 2013. The survey's items included the types of treated cancer (14 categories: stomach, colon, breast, liver, biliary tract, pancreatic, prostate, esophageal, lung, renal, urinary tract, testicular, hematopoietic, and others) and the first five types were defined as major cancers. The data were analyzed between hospitals and clinics. The response rate was about 60%, and of 177 hospitals and 281 clinics, 54 hospitals (30%) and 10 clinics (3%) reported the types of cancer. The median number of cancer types in hospitals was significantly greater than that of clinics (4 [interquartile range 3.0-7.8]) vs. 1 [1.0-1.8], P < 0.01). The prevalence of hospitals treating at least one of five major cancers was significantly greater than that of clinics (96% vs. 30%, P < 0.01). The prevalence of clinics treating prostate cancer was significantly greater than that of hospitals (31% vs. 70%, P = 0.03). In conclusion, most types of cancer are treated at small-to-middle-sized hospitals, except for prostate cancer, providing basic information about cancer treatment in rural communities of Japan.

Aim/introduction: Primary Sjögren's syndrome (pSS) is a prototypical systemic autoimmune disease that manifests with various signs and symptoms. Although some studies have examined these manifestations over the long-term course of the disease, the association between initial clinical and immunological factors and subsequent long-term manifestations has not been fully elucidated. The aim of this study is to identify initial clinical and immunological factors associated with subsequent manifestations in patients with pSS., Method: A retrospective review was performed in pSS patients who were followed up over a 10-year period in our department. Clinical and immunological data, including serum immunoglobulin (Ig) and autoantibody levels, were collected and statistically analyzed., Result: We analyzed 91 patients who were followed up in our department. The proportion of patients with extraglandular involvement decreased from 90% to 73%, while eight patients developed extraglandular organ involvement. Extraglandular involvement at 10 years more frequently occurred in patients with hyper-IgG than those without hyper-IgG at initial testing (P < 0.01). Extraglandular organ involvement at 10 years more frequently occurred in rheumatoid factor (RF)-positive patients at the time of SS diagnosis (P < 0.05). Malignancy occurred in 9% of patients. Age, lower CH50 and thrombocytopenia were significantly associated with malignancy. Extraglandular organ involvement was associated with the presence of hyper-IgG and RF positivity (P < 0.01 and P < 0.05)., Conclusion: Our study identified important initial clinical and immunological factors associated with subsequent manifestations in patients with pSS over a long follow-up period. pSS patients with RF and hyper-IgG at diagnosis may have a higher risk of subsequent extraglandular involvement., (© 2018 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Background: Because of aggressive immunosuppression, heart transplant recipients have a high risk of de novo malignancy, which is a major cause of death and worse prognosis, regardless of the type. However, the impact of de novo malignancy on Japanese heart transplant recipients is unknown., Methods: We analyzed 103 Japanese heart transplant recipients over 18-years-old at the time of transplantation between April 1999 and April 2017. Patient characteristics and prognosis were compared between heart transplant recipients with or without de novo malignancy after heart transplantation (HTx). Additionally, univariate and multivariate analyses for the risk factors of de novo malignancy after HTx were performed., Results: De novo malignancy developed in 7 patients (6.8%; post-transplant lymphoproliferative disorders, n=3; Bowen's disease, n=1; colon cancer, n=2; bladder cancer, n=1). Follow-up time and previous antibody mediated rejection (AMR)≥grade 1 were risk factors of de novo malignancy after HTx in multivariate analysis (OR: 1.19, 95% CI: 1.00-1.42, p=0.043; and OR: 10.7, 95% CI: 1.37-83.68, p=0.038, respectively). History of malignancy was a potential risk factor, albeit not significant (OR: 23.05, 95% CI: 0.99-534.53, p=0.071). The survival rates in patients with de novo malignancy was significantly lower than in those without de novo malignancy (3-year survival rate: 100% versus 67%, p=0.0025)., Conclusions: Long follow-up time and previous AMR≥grade 1 were risk factors of de novo malignancy after HTx. Japanese heart transplant recipients with de novo malignancy have worse prognosis; therefore, screening examinations are important for early diagnosis., (Copyright © 2018 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: In Japan, freeze-dried live attenuated varicella-zoster vaccine is available for adults aged ≥50 years to prevent herpes zoster. However, limited evidence has been accumulated regarding vaccine safety for patients with underlying illnesses, who have been considered as the high-risk group for herpes zoster., Methods: A prospective cohort study of 1200 healthy adults and 300 patients with underlying illnesses such as malignancy, diabetes mellitus, autoimmune diseases, and renal diseases was conducted. All subjects were vaccinated and then their adverse events (AEs) were followed for 28 days after vaccination. Key safety measures included any AEs, severe AEs (SAEs), and vaccine-related AEs such as injection-site AEs and systemic AEs. The frequencies and 95% confidence intervals of AEs were calculated., Results: During the follow-up period, 2 SAEs (bone fracture and acute cholecystitis) among healthy adults and 1 SAE (disseminated mycobacteriosis) among patients with underlying illnesses were reported, although none of them was diagnosed as vaccine-related. Vaccine-related AEs were reported in 42% of healthy adults and patients with underlying illnesses, and the proportions were similar between the groups. The most frequent AEs were injection-site AEs in both groups (i.e., 41 and 39%), and systemic AEs were observed in 4% of both groups. Only among healthy adults, those with a history of herpes zoster were more likely to report injection-site AEs than those without a history of herpes zoster (53% vs 39%)., Conclusions: The present study confirmed the safety of freeze-dried, live attenuated varicella-zoster vaccine even in patients with underlying illnesses. A history of herpes zoster might be related to development of injection-site AEs in healthy adults., Trial Registration: The study was prospectively registered on Japic-Clinical Trials Information as JapicCTI-163415 on October 31, 2016.

Autoantibodies in patients with myositis may associate with specific clinical manifestations. This study aimed to identify a subset of patients with myositis carrying antinuclear matrix protein 2 (anti-NXP-2) antibodies using an unlabeled immunoprecipitation (IP) assay, and clarify the features of these patients in a Chinese cohort. We developed novel methods for unlabeled protein IP and immunoblotting of Myc-tagged truncated NXP-2 fragments for anti-NXP-2 detection. The sera of 120 Chinese adult patients with myositis were screened for anti-NXP-2 by IP and immunoblot. Anti-NXP-2 antibodies were detected in 10 of the 120 patients (8.3%) using the established unlabeled protein IP and immunoblotting, with 70% (7/10) exhibiting either heliotrope rash or Gottron's papules. All 10 anti-NXP-2-positive patients exhibited myopathy and 60% complained of dysphagia. Severe diffuse calcinosis (10%) and nasopharyngeal carcinoma (10%) were each only present in single anti-NXP-2-positive patients with myositis. Antibodies against Ro-52 were found in four living but not in three deceased anti-NXP-2-positive patients. A comprehensive review of 13 anti-NXP-2 studies demonstrated markedly lower anti-NXP-2 prevalence among adult patients with myositis and lower association of anti-NXP-2 with calcinosis in Japan, China, and Hungary than in the USA and Italy. Anti-NXP-2 antibody association with internal malignancy in adult patients varied from 0 to 50% across different studies. A novel IP assay was developed to detect patients with myositis expressing anti-NXP-2. Calcinosis and malignancy are rare in Chinese adult patients with myositis positive for anti-NXP-2. Literature review indicated highest anti-NXP-2 prevalence and association of anti-NXP-2 with calcinosis in US and Italian myositis cohorts.

Ovarian cryopreservation and autotransplantation could be of potential value for preservation of fertility in the patients with various malignancies. Ovarian tissue should be cryopreserved actively for fertility preservation, but stored tissue should be autotransplanted with much caution until reliable methods are established to detect minimal residual disease in grafts in precise and reproducible manners. [Copyright &y& Elsevier]