Objective: There are few reports of the long-term outcomes of elderlypatients with prostate cancer. We analyzed data from our institution from the past 12years, including the patient history, treatment methods, and prognosis of patients withprostate cancer aged 80 years or more.

Patients and Methods: A total of 179 cases of prostate cancer in patientsaged 80 years or more were retrospectively evaluated. We divided them chronologically intogroups A, B, C, and D: Group A included 40 cases from 2002–2004; Group B, 48 cases from2005–2007; Group C, 46 cases from 2008–2010; and Group D, 45 cases from 2011–2013.

Results: Sixty-one (30%) patients changed treatment course. Interestingly,no cancer deaths occurred in the patients who changed treatment course. Although 14 (7.8%)cancer deaths occurred (A: B: C: D = 4: 4: 6: 0, respectively), all occurred in 2011 orlater.

Conclusion: In our study, over 50 patients who underwent treatment survivedfor 5 years or more. By treating prostate cancer in elderly patients when appropriate, wecan lower the mortality rate due to prostate cancer. Our results support the activetreatment of prostate cancer in elderly patients.

Inflammatory bowel disease is a chronic disease of unknown origin that requires long-term treatment. The optical duration of maintenance treatment once remission has been achieved remains unclear. When discussing a de-escalation strategy, not only the likelihood of relapse but also, the outcome of retreatment for relapse after de-escalation should be considered. Previous evidence has demonstrated controversial results for risk factors for relapse after de-escalation due to the various definitions of remission and relapse. In fact, endoscopic or histologic remission has been suggested as a treatment target; however, it might not always be indicative of a successful drug withdrawal. For better risk stratification of relapse after de-escalation, it may be necessary to evaluate both the current and previous treatments. Following de-escalation, biomarkers should be closely monitored. In addition to the risk of relapse, a comprehensive understanding of the overall outcome, such as the long-term safety, patient quality of life, and impact on healthcare costs, is necessary. Therefore, a shared decision-making with patients on a case-by-case basis is imperative.

Capsule endoscopy (CE) is emerging as an important investigation in inflammatory bowel disease (IBD); common types include the standard small bowel CE and colon CE. More recently, the pan-enteric CE was developed to assess the large and small bowel in patients with Crohn’s disease (CD). Emerging indications include noninvasive assessment for mucosal healing (both in the small bowel and the colon) and detection of postoperative recurrence in patients with CD. Given the increasing adoption, several CE scoring systems have been specifically developed for IBD. The greatest concern with performing CE, particularly in CD, is capsule retention, but this can be overcome by performing cross-sectional imaging such as magnetic resonance enterography and using patency capsules before performing the procedure. The development of software for automated detection of mucosal abnormalities typically seen in IBD may further increase its adoption.

Background/Aims: Risks of long-term steroid use in patients with ulcerative colitis (UC) outweigh the benefits, thus dosing should be tapered once a response is achieved. Colonoscopy is a key technique for assessing disease severity and optimizing treatment involving steroids. This retrospective longitudinal cohort study of patients with UC explored factors associated with the duration of systemic steroid use. Methods: The Japan Medical Data Center database, an employer-based insurance claims database, was used to select individuals initiating prednisolone, with a prescription issued between January 1, 2010, and January 31, 2018. The study included adults with a confirmed diagnosis of UC, who had received ≥1 year of continuous treatment with 5-aminosalicylic acid, biologics, or thiopurine. Factors associated with prednisolone duration were assessed using a multivariate regression model. Results: Median duration of prednisolone treatment was 98 days, and colonoscopy was performed ≤1 month before or at the first prescription of prednisolone (index date) in 32.8% of patients (607/1,853). Shorter durations of prednisolone treatment were associated with colonoscopy ≤1 month before or at the index date and higher prednisolone dose at index date, with incidence rate ratios (IRRs) of 0.776 (95% confidence interval [CI], 0.682–0.884; P<0.001) and 0.998 (95% CI, 0.996–1.000; P=0.018), respectively. Charlson Comorbidity Index scores of 1 and ≥2 predicted longer prednisolone treatment (IRR, 1.332; 95% CI, 1.174–1.511; P<0.001 and IRR, 1.599; 95% CI, 1.357–1.885; P<0.001, respectively). Conclusions Performing colonoscopy before or at the time of initiating steroid was associated with a shorter duration of steroid use in patients with UC.

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

BACKGROUND: For an effective bone graft for reconstruction of the maxillofacial region, an adequate vascular network will be required to supply blood, osteoprogenitor cells, and growth factors. We previously reported that the secretomes of bone marrow-derived mesenchymal stem cells (MSC-CM) contain numerous growth factors such as insulin-like growth factor (IGF)-1, transforming growth factor (TGF)-β1, and vascular endothelial growth factor (VEGF), which can affect the cellular characteristics and behavior of regenerating bone cells. We hypothesized that angiogenesis is an important step for bone regeneration, and VEGF is one of the crucial factors in MSC-CM that would enhance its osteogenic potential. In the present study, we focused on VEGF in MSC-CM and evaluated the angiogenic and osteogenic potentials of MSC-CM for bone regeneration. METHODS: Cytokines in MSC-CM were measured by enzyme-linked immunosorbent assay (ELISA). Human umbilical vein endothelial cells (HUVECs) were cultured with MSC-CM or MSC-CM with anti-VEGF antibody (MSC-CM + anti-VEGF) for neutralization, and tube formation was evaluated. For the evaluation of bone and blood vessel formation with micro-computed tomography (micro-CT) and for the histological and immunohistochemical analyses, a rat calvarial bone defect model was used. RESULTS: The concentrations of IGF-1, VEGF, and TGF-β1 in MSC-CM were 1515.6 ± 211.8 pg/mL, 465.8 ± 108.8 pg/mL, and 339.8 ± 14.4 pg/mL, respectively. Tube formation of HUVECs, bone formation, and blood vessel formation were increased in the MSC-CM group but decreased in the MSC-CM + anti-VEGF group. Histological findings suggested that new bone formation in the entire defect was observed in the MSC-CM group although it was decreased in the MSC-CM + anti-VEGF group. Immunohistochemistry indicated that angiogenesis and migration of endogenous stem cells were much more abundant in the MSC-CM group than in the MSC-CM + anti-VEGF group. CONCLUSIONS: VEGF is considered a crucial factor in MSC-CM, and MSC-CM is proposed to be an adequate therapeutic agent for bone regeneration with angiogenesis.
Animals ; Blood Vessels ; Bone Regeneration ; Culture Media, Conditioned ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Human Umbilical Vein Endothelial Cells ; Humans* ; Immunohistochemistry ; Insulin-Like Growth Factor I ; Intercellular Signaling Peptides and Proteins ; Mesenchymal Stromal Cells* ; Osteogenesis ; Rats ; Stem Cells ; Transforming Growth Factors ; Transplants ; Vascular Endothelial Growth Factor A

Extracolonic involvement of the gastrointestinal tract is extremely uncommon in ulcerative colitis (UC) and rarely found in the upper gastrointestinal tract or in postoperative cases since it typically responds to steroids. Here we report a case of UC complicated by extensive ileal inflammation that was refractory to steroids. A 20-year-old man was diagnosed with UC of typical pancolitis without ileal involvement and started treatment with pH-dependent mesalazine and oral prednisolone. Although his symptoms transiently resolved, the condition flared when the steroid dose was tapered down. Computed tomography revealed marked thickening of the ileal wall, and capsule endoscopy and balloon-assisted enteroscopy found diffuse mucosal inflammation with ulcers in the ileum. On the contrary, the inflammation in the colon and rectum was improving. Since the response to the second steroid course was inadequate, treatment with adalimumab and 6-mercaptopurine was initiated and finally achieved clinical and endoscopic remission. The investigation of small intestinal lesions is necessary in patients with UC whose clinical deterioration cannot be explained by colonic lesions.
6-Mercaptopurine ; Adalimumab* ; Capsule Endoscopy ; Colitis, Ulcerative* ; Colon ; Enteritis* ; Gastrointestinal Tract ; Humans ; Ileum ; Inflammation ; Inflammatory Bowel Diseases ; Mesalamine ; Prednisolone ; Rectum ; Steroids ; Ulcer* ; Upper Gastrointestinal Tract ; Young Adult

BACKGROUND/AIMS: Oral mesalazine is an important treatment for ulcerative colitis (UC), and non-adherence to mesalazine increases the risk of relapse. Controlled-release (CR) mesalazine has 2 formulations: tablets and granules. The relative acceptabilities of these formulations may influence patient adherence; however, they have not been compared to date. This study aimed to evaluate the acceptabilities of the 2 formulations of CR mesalazine in relation to patient adherence using a crossover questionnaire survey. METHODS: UC patients were randomly assigned to 2 groups in a 1:1 ratio. Patients in each group took either 4 g of CR mesalazine tablets or granules for 6 to 9 weeks, and then switched to 4 g of the other formulation for a further 6 to 9 weeks. The acceptability and efficacy were evaluated by questionnaires, and adherence was assessed using a visual analog scale. The difference in acceptabilities between the 2 formulations and its impact on adherence were assessed. RESULTS: A total of 49 patients were prospectively enrolled and 33 patients were included in the analysis. Significantly more patients found the tablets to be less acceptable than the granules (76% vs. 33%, P=0.0005). The granules were preferable to the tablets when the 2 formulations were compared directly (73% vs. 21%, P=0.004), for their portability, size, and numbers of pills. The adherence rate was slightly better among patients taking the granules (94% vs. 91%) during the observation period, but the difference was not significant (P=0.139). CONCLUSIONS: CR mesalazine granules are more acceptable than tablets, and may therefore be a better option for long-term medication.
Colitis, Ulcerative ; Drug Compounding ; Humans ; Medication Adherence ; Mesalamine ; Patient Acceptance of Health Care ; Patient Compliance ; Prospective Studies ; Recurrence ; Tablets ; Ulcer ; Visual Analog Scale

Background/Aims: A subgroup analysis was conducted in Japanese patients with moderate to severe ulcerative colitis (UC) enrolled in the phase 3 VISIBLE 1 study, which evaluated the safety and efficacy of a new vedolizumab subcutaneous (SC) formulation. Methods: Eligible patients received open-label infusions of vedolizumab 300 mg intravenous (IV) at weeks 0 and 2 in the induction phase. Patients with clinical response by complete Mayo score at week 6 entered the double-blind maintenance phase and were randomized to vedolizumab 108 mg SC every 2 weeks, placebo, or vedolizumab 300 mg IV every 8 weeks. The primary endpoint was clinical remission (complete Mayo score ≤ 2 points; no individual subscore > 1 point) at week 52. Results: Of 49 patients who entered the induction phase, 22 out of 49 patients (45%) had clinical response at week 6 and were randomized to vedolizumab 108 mg SC (n = 10), placebo (n = 10), or vedolizumab 300 mg IV (n = 2). At week 52, 4 out of 10 patients (40%) who received vedolizumab SC had clinical remission versus 2 out of 10 patients (20%) who received placebo (difference: 20% [95% confidence interval, –27.9 to 61.8]). Two patients (2/10, 20%) who received vedolizumab SC experienced an injection-site reaction versus none who received placebo. Conclusions Our results indicate that the efficacy of vedolizumab SC in a subgroup of Japanese patients with UC are similar with those in the overall VISIBLE 1 study population, and with those established with vedolizumab IV. The safety and tolerability of vedolizumab SC were generally similar to that established for vedolizumab IV. (ClinicalTrials.gov ID NCT02611830; EudraCT 2015-000480-14)

Background/Aims: Mirikizumab is a p19-directed anti-interleukin-23 antibody with potential efficacy against ulcerative colitis (UC). We evaluated the efficacy and safety of mirikizumab in a Japanese subpopulation with moderately to severely active UC from the LUCENT-1 and LUCENT-2 studies. Methods: LUCENT-1 and LUCENT-2 were phase 3, randomized, double-blind, placebo-controlled trials of mirikizumab therapy in adults with moderately to severely active UC. LUCENT-1 was a 12-week induction trial where patients were randomized 3:1 to receive intravenous mirikizumab 300 mg or placebo every 4 weeks (Q4W). Patients achieving a clinical response with mirikizumab following the induction study were re-randomized 2:1 to double-blind treatment with either mirikizumab 200 mg or placebo subcutaneously Q4W during the 40-week maintenance study. The primary outcomes were clinical remission at week 12 of LUCENT-1 and week 40 of LUCENT-2. Results: A total of 137 patients enrolled in Japan were randomized to mirikizumab (n = 102) or placebo (n = 35). Compared with placebo, patients who received mirikizumab showed numerically higher clinical remission at week 12 of induction (32.4% [n = 33] vs. 2.9% [n = 1]) and at week 40 of maintenance (48.9% [n = 23] vs. 28.0% [n = 7]). A greater number of patients achieved key secondary endpoints in the mirikizumab group compared with placebo. The frequency of treatment-emergent adverse events was similar across mirikizumab and placebo groups. Efficacy and safety results observed in the Japanese subpopulation were generally consistent with those in the overall population. Conclusions Mirikizumab induction and maintenance treatments were effective in Japanese patients with moderately to severely active UC. No new safety concerns were identified.