Objective: The purposes of this trial were to demonstrate the feasibility and effectiveness of the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced cervical cancer patients in the phase I/II prospective clinical trial. Methods: Patients with FIGO stage IB2-IVA uterine cervical cancer pretreatment width of which was ≥5 cm measured by magnetic resonance imaging were eligible for this clinical trial. The protocol therapy included 30–30.6 Gy in 15–17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP, followed by 24 Gy in 4 fractions of HBT and pelvic radiotherapy with a central shield up to 50–50.4 Gy in 25–28 fractions. The primary endpoint of phase II part was 2-year pelvic progression-free survival (PPFS) rate higher than historical control of 64%. Results: Between October 2015 and October 2019, 73 patients were enrolled in the initial registration and 52 patients proceeded to the secondary registration. With the median follow-up period of 37.3 months (range, 13.9–52.9 months), the 2- PPFS was 80.7% (90% confidence interval [CI]=69.7%–88%). Because the lower range of 90% CI of 2-year PPFS was 69.7%, which was higher than the historical control ICBT data of 64%, therefore, the primary endpoint of this study was met. Conclusion The effectiveness of HBT were demonstrated by a prospective clinical study. Because the dose goal determined in the protocol was lower than 85 Gy, there is room in improvement for local control. A higher dose might have been needed for tumors with poor responses.

Background/Aims: Crohn’s disease is a chronic disorder; therefore, it is essential to investigate long-term safety and efficacy of treatments. This study assessed the safety and effectiveness of adalimumab for up to 3 years in Japanese patients with Crohn’s disease in real-world settings. Methods: This was a multicenter, single-cohort, observational study of patients with Crohn’s disease. Safety assessments included incidence of adverse drug reactions. Effectiveness assessments included clinical remission, mucosal healing, and Work Productivity and Activity Impairment (WPAI). Results: The safety and effectiveness analysis populations comprised 389 and 310 patients, respectively. Mean (standard deviation) exposure to adalimumab in the safety analysis population was 793.4 (402.8) days, with a 58.1% retention rate. A total of 105 patients (27.0%) and 43 patients (11.1%) experienced adverse drug reactions and serious adverse drug reactions, respectively, with no patient reporting tuberculosis or hepatitis B. Infections and serious infections were reported in 37 patients (9.5%) and 17 patients (4.4%), respectively. Malignancy was reported as an adverse drug reaction in 2 patients (0.5%). Remission rate increased from 37.8% (98/259) at baseline to 73.9% (167/226) at week 4 and remained > 70% over 3 years. Proportion of patients without mucosal ulcerations increased from 2.7% (2/73) at baseline to 42.3% (11/26) between years > 2 to ≤ 3. WPAI improvement started at 4 weeks, with the overall work impairment score improving from 42.7 (n = 102) at baseline to 26.9 (n = 84) at 4 weeks. Conclusions Results from this study confirm the long-term safety and effectiveness of adalimumab treatment in Japanese patients with Crohn’s disease in the real-world setting.

Trousseau's syndrome is a condition in which thromboembolic events are triggered by hypercoagulation caused by a malignancy. Here, we report two cases in which gynecologic cancer was detected after cerebral infarction. Patient 1 was a 66-year-old gravida 0, para 0 who presented with left-sided arm and leg weakness. Head magnetic resonance imaging (MRI) facilitated a diagnosis of cerebral infarction. Subsequent contrast computed tomography (CT) revealed an ovarian tumor, and she underwent surgery on day 8 after admission. The tumor was diagnosed as ovarian clear cell carcinoma on pathological examination. She received adjuvant chemotherapy and the cancer has not progressed in more than 2 years after the surgery. Patient 2 was a 41-year-old gravida 1, para 1 who presented with impairment of consciousness, right hemiplegia, and aphasia. Head MRI facilitated a diagnosis of cerebral infarction. Contrast MRI and contrast CT findings were suggestive of endometrial cancer, and she underwent surgery on day 19 after admission. The cancer was diagnosed as grade 3 endometrial cancer on pathological analysis. She received adjuvant chemotherapy and the cancer has not progressed in more than 4 years after the surgery. Although treatment of the primary disease is considered to affect prognosis in Trousseau’s syndrome, many patients have poor survival prospects because, when detected, their cancer is too advanced to be treated surgically. These cases illustrate the need for close cooperation with other departments such as neurology and cerebrovascular surgery to ensure that these cancers are diagnosed quickly and the opportunity to start multimodality treatment is not missed.

Objective: To create an authorized translation of the “definition of palliative care” according to WHO using the Delphi method. Methods: Through a palliative care association council (hereafter referred to as the “council”) composed of 18 academic organizations, this research aimed to create an authorized translation draft and develop a consensus for it using the Delphi method according to 54 experts, three from each organization. The main clause and nine subordinate clauses of the document were evaluated from “not at all appropriate” (1 point) to “completely appropriate” (9 points). The standard for consensus was if the median was 7 points or above, or if there was a difference of 5 points or less between the maximum and minimum. The council created an authorized translation in light of the consensus status. Results: Three rounds of the Delphi method were performed; the response rates were 100%, 93%, and 91% respectively. As 30% of the clauses reached the predetermined standard for consensus, the council discussed and considered, established an authorized translation draft, and made a decision upon public comment from each academic organization. Conclusion: Academic organizations associated with palliative care jointly created an authorized translation for the “definition of palliative care” according to WHO.

BACKGROUND/AIMS: An interim analysis of post-marketing surveillance of CT-P13, an infliximab biosimilar, was performed to evaluate its safety and efficacy in Japanese patients with inflammatory bowel disease.METHODS: Patients were prospectively enrolled between November 2014 and March 2017, after the launch of CT-P13 in Japan, and case report forms of patients followed for at least 4 months were analyzed as of July 2018.RESULTS: Of 523 patients in the analysis set, 372 remained on CT-P13 therapy, while 54 (20.2%) of 267 patients with Crohn’s disease, and 97 (37.9%) of 256 patients with ulcerative colitis were withdrawn during follow-up. A total of 144 adverse drug reactions (ADRs) were reported in 106 patients (20.3%). Infusion reaction was the most frequent ADR observed in 49 patients (9.4%). Efficacy parameters decreased immediately after the start of treatment in naïve patients to anti-tumor necrosis factor-α antibody. In the patients switched from originator infliximab for nonmedical reasons, the decreased parameters due to proceeded treatment with the originator were maintained in low ranges, and the treatment continuation rate was high with low ADR incidence. In contrast, in patients switched for medical reasons such as adverse event or loss of response, the incidence of ADRs was high. However, the efficacy parameters were improved, and the treatment continuation rate was not significantly different from that of the naïve patient group.CONCLUSIONS: In this interim analysis, CT-P13 was comparable to the originator infliximab with respect to ADRs and efficacy, and is therefore considered to be a cost-efficient interchangeable biosimilar for Japanese patients with inflammatory bowel disease.
Asian Continental Ancestry Group ; Colitis, Ulcerative ; Drug-Related Side Effects and Adverse Reactions ; Follow-Up Studies ; Humans ; Incidence ; Inflammatory Bowel Diseases ; Infliximab ; Japan ; Necrosis ; Prospective Studies

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease of the gastrointestinal tract, with increasing prevalence worldwide. IBD Ahead is an international educational program that aims to explore questions commonly raised by clinicians about various areas of IBD care and to consolidate available published evidence and expert opinion into a consensus for the optimization of IBD management. Given differences in the epidemiology, clinical and genetic characteristics, management, and prognosis of IBD between patients in Japan and the rest of the world, this statement was formulated as the result of literature reviews and discussions among Japanese experts as part of the IBD Ahead program to consolidate statements of factors for disease prognosis in IBD. Evidence levels were assigned to summary statements in the following categories: disease progression in CD and UC; surgery, hospitalization, intestinal failure, and permanent stoma in CD; acute severe UC; colectomy in UC; and colorectal carcinoma and dysplasia in IBD. The goal is that this statement can aid in the optimization of the treatment strategy for Japanese patients with IBD and help identify high-risk patients that require early intervention, to provide a better long-term prognosis in these patients.
Asian Continental Ancestry Group ; Colectomy ; Colitis, Ulcerative ; Colorectal Neoplasms ; Consensus ; Crohn Disease ; Disease Management* ; Disease Progression ; Early Intervention (Education) ; Epidemiology ; Expert Testimony ; Gastrointestinal Tract ; Hospitalization ; Humans ; Inflammatory Bowel Diseases* ; Japan* ; Prevalence ; Prognosis

No abstract available.
Crohn Disease* ; Food, Formulated* ; Humans ; Infliximab*

BACKGROUND/AIMS: Anti-tumor necrosis factor drugs (anti-TNF) and thiopurines are important treatment options in patients with inflammatory bowel disease (IBD), including during pregnancy. However, there are limited data on the benefit/risk profile of anti-TNF and thiopurines during pregnancy in Asia. The aim of this study was to analyze pregnancy outcomes of female Japanese IBD patients treated with anti-TNF and/or thiopurines. METHODS: This cross-sectional study assessed pregnancy outcomes in 72 women with IBD. Pregnancy outcomes were compared among 31 pregnancies without exposure to infliximab (IFX), adalimumab (ADA), or thiopurines; 24 pregnancies with exposure to anti-TNF treatment (23 IFX, 1 ADA); 7 pregnancies with exposure to thiopurines alone; and 10 pregnancies with exposure to both IFX and thiopurines. RESULTS: Thirty-five of the 41 pregnancies (85.3%) that were exposed to anti-TNF treatment and/or thiopurines resulted in live births after a median gestational period of 38 weeks. Of the 35 live births, 3 involved premature deliveries; 7, low birth weight; and 1, a congenital abnormality. There were 6 spontaneous abortions in pregnancies that were exposed to anti-TNF treatment (17.7%). Pregnancy outcomes among the 4 groups were similar, except for the rate of spontaneous abortions (P =0.037). CONCLUSIONS: Exposure to anti-TNF treatment or thiopurines during pregnancy was not related to a higher incidence of adverse pregnancy outcomes in Japanese IBD patients except for spontaneous abortion.
Adalimumab ; Abortion, Spontaneous ; Asia ; Asian Continental Ancestry Group ; Congenital Abnormalities ; Cross-Sectional Studies ; Female ; Humans ; Incidence ; Infliximab ; Infant, Low Birth Weight ; Infant, Newborn ; Inflammatory Bowel Diseases* ; Japan* ; Live Birth ; Necrosis* ; Pregnancy ; Pregnancy Outcome* ; Pregnancy*

BACKGROUND: Management of postprandial hyperglycemia is a key aspect in diabetes treatment. We developed a novel system to measure glucose area under the curve (AUC) using minimally invasive interstitial fluid extraction technology (MIET) for simple monitoring of postprandial glucose excursions. In this study, we evaluated the relationship between our system and continuous glucose monitoring (CGM) by comparing glucose AUC obtained using MIET with that obtained using CGM for a long duration. METHODS: Twenty diabetic inpatients wearing a CGM system were enrolled. For MIET measurement, a plastic microneedle array was applied to the skin as pretreatment, and hydrogels were placed on the pretreated area to collect interstitial fluid. Hydrogels were replaced every 2 or 4 hours and AUC was predicted on the basis of glucose and sodium ion levels. RESULTS: AUC predicted by MIET correlated well with that measured by CGM (r=0.93). Good performances of both consecutive 2- and 4-hour measurements were observed (measurement error: 11.7%±10.2% for 2 hours and 11.1%±7.9% for 4 hours), indicating the possibility of repetitive measurements up to 8 hours. The influence of neither glucose fluctuation nor average glucose level over the measurement accuracy was observed through 8 hours. CONCLUSION: Our system showed good relationship with AUC values from CGM up to 8 hours, indicating that single pretreatment can cover a large portion of glucose excursion in a day. These results indicated possibility of our system to contribute to convenient monitoring of glucose excursions for a long duration.
Area Under Curve* ; Extracellular Fluid ; Glucose* ; Humans ; Hydrogel ; Hydrogels ; Hyperglycemia ; Inpatients ; Plastics ; Skin ; Sodium

Rikkunshito is comprised of 8 crude drugs and is used for the treatment of gastrointestinal dysfunctions such as anorexia and heavy stomach feeling. These symptoms are often caused by delay in gastric emptying. Cisplatin is a representative cancer chemotherapeutic drug with severe adverse effects such as anorexia and nausea, that gives rise to a delay in gastric emptying. However, it is still unknown whether rikkunshito has effects on improving the delayed gastric emptying induced by cisplatin. In the present study, we examined the effects of rikkunshito (an Atractylodis rhizoma-containing formula) on cisplatin-induced delay in gastric emptying in the rat. Rikkunshito improved this. Among the crude drugs that comprise rikkunshito, Atractylodis rhizoma, Ginseng radix, Poria and Aurantii nobilis pericarpium individually improved the delay in gastric emptying, suggesting that they all contribute to the action of rikkunshito. Moreover, the effects of these 4 crude drugs in combinations were also examined, and as a result, tended to be stronger when Atractylodis rhizoma was included. On the other hand, when Atractylodis rhizoma was excluded from rikkunshito, the effects were weaker. Meanwhile, atractylenolide III, a specific chemical constituent of Atractylodis rhizoma, improved delay in gastric emptying in a manner similar to that of rikkunshito with Atractylodis rhizoma. These results, taken together, suggest that Atractylodis rhizoma likely contributes greatly to the improving effect of rikkunshito on cisplatin-induced delay in gastric emptying.