Cluster analysis defines four groups of Japanese patients with adult-onset Still's disease.

OBJECTIVES: To define groups and characterize differences in the prognosis of patients with adult-onset Still's disease (AOSD). METHODS: We performed a retrospective cohort study. Patients with AOSD were grouped using hierarchical unsupervised cluster analysis according to age, sex, clinical features, and laboratory data. The primary endpoints were overall survival and drug-free remission rate. RESULTS: A total of 153 patients with AOSD were placed into four clusters. Those in Cluster 1 had a young onset, tended to be female, and had fewer complications and moderate ferritin concentrations. Those in Cluster 2 had a young onset and had more complications and higher ferritin concentrations. Those in Cluster 3 had a young onset, tended to be male, and had no lymphadenopathy and fewer complications. Those in Cluster 4 had an older onset, tended to be female, and had more complications and higher ferritin concentrations. Overall survival tended to be lower (P = .0539) in Cluster 4, and drug-free remission was higher in Clusters 1, 2, and 3 [hazard ratios (HRs) 2.19, 3.37, and 3.62 vs. Cluster 4, respectively]. CONCLUSIONS: Four groups of AOSD that have distinct clinical manifestations, ferritin concentrations, severity, and drug-free remission rate were identified, which were lowest in Cluster 4. Graphical Abstract.

Usefulness of the severity classification for predicting drug-free remission in Japanese patients with adult-onset Still's disease.

OBJECTIVES: To investigate the usefulness of severity classification for predicting outcomes in patients with adult-onset Still's disease (AOSD). METHODS: This was a multi-centre retrospective cohort study. AOSD patients were classified into mild, moderate, and severe groups based on severity classification (Japanese Ministry of Health, Labour and Welfare) during the initial treatment, and clinical features were compared among these groups. The primary endpoints were the AOSD-related mortality and drug-free remission rate. For comparison, the same analysis was performed in parallel for patient groups stratified by the modified Pouchot systemic score. RESULTS: According to severity classification, 49 (35%), 37 (26%), and 56 patients (39%) were classified into mild, moderate, and severe groups, respectively. Patients in the severe group showed higher frequency of severe complications and the use of biological agents. Although AOSD-related survival was not significantly different (p = .0776), four of the five fatal cases were classified into the severe group. The severe group showed a reduced rate of drug-free remission (p = .0125). Patient groups classified by systemic score did not correlate with survival or drug-free remission. CONCLUSIONS: Severity classification is useful for predicting outcomes in patients with AOSD.

Impact of dietary compositions and patterns on the prevalence of nonalcoholic fatty liver disease in Japanese men: a cross-sectional study.

BACKGROUND: This study aimed to examine the impact of dietary compositions and patterns on nonalcoholic fatty liver disease (NAFLD) morbidity in Japanese men. METHODS: We conducted a cross-sectional study of 281 individuals who underwent comprehensive medical examinations during health screening. Dietary intake was assessed using a semi-quantitative food frequency questionnaire, and factor analysis was performed to detect dietary patterns. NAFLD was diagnosed by the presence of fatty liver on abdominal ultrasonography in nondrinkers (< 30 g/day), and patients were categorized into control (n = 192) and NAFLD groups (n = 89). RESULTS: Compared with the control group, the NAFLD group consumed fewer mushrooms. Three dietary patterns were identified, namely, a healthy pattern, a western pattern, and a snack pattern. The score of healthy pattern was negatively correlated with the risk of NAFLD. Compared with the lowest tertile of the healthy pattern, the middle tertile was associated with a lower risk of NAFLD after adjusting for age, physical activity, and smoking (odds ratio: 0.47, 95% confidence interval: 0.25-0.91). After further adjustments for body mass index, the middle tertile was associated with a lower risk of NAFLD (odds ratio: 0.46, 95% confidence interval: 0.23-0.92). CONCLUSIONS: A healthy dietary pattern comprising frequent intake of seaweeds, vegetables, mushrooms, pulses, and potatoes and starches was associated with a lower risk of NAFLD in Japanese men. In our opinion, this healthy pattern closely resembles the Japanese Washoku diet, indicating that adherence to Washoku may help prevent NAFLD.

Assessment of surgical outcomes of off-clamp open partial nephrectomy without renorrhaphy for ≥T1b renal tumours.

PURPOSE: To assess the surgical outcomes of off-clamp open partial nephrectomy without renorrhaphy. In the era of robot-assisted surgeries, open partial nephrectomy remains a surgical option for ≥ T1b renal tumours. Although the necessity of renal pedicle clamping and renorrhaphy in open partial nephrectomy for larger tumours remains to be discussed, reports on this issue are rare. METHODS: Twenty-seven open partial nephrectomies for ≥ T1b renal tumours were performed without renal pedicle clamping or renorrhaphy. A soft coagulation system was used to control bleeding from the resection bed. Surgical results, complications, and predictors of perioperative estimated glomerular filtration rate (eGFR) preservation at 1 month and 3 months after surgery were analysed. RESULTS: The median estimated volume of blood loss was 420 mL. The rates of perioperative eGFR preservation were 88.9 and 87.3% at 1 and 3 months after surgery, respectively. Tumour size was an independent predictor of perioperative eGFR preservation at 1 month after surgery, whereas age and exophytic/endophytic properties of the tumour were independent predictors of perioperative eGFR preservation at 3 months after surgery. CONCLUSION: Open partial nephrectomy without renal pedicle clamping or renorrhaphy could be safely performed for ≥ T1b renal tumours, even when tumours were entirely endophytic and located close to the renal pedicle. Mild perioperative eGFR reduction was observed. Although surgical indications should be carefully considered in these cases, off-clamp open partial nephrectomy without renorrhaphy is a feasible procedure for patients with ≥ T1b renal tumours.

Clinical features of elderly-onset Adult-onset Still's disease.

OBJECTIVES: To clarify the characteristics of patients with elderly-onset Adult-onset Still's disease (AOSD). METHODS: Patients were classified into elderly-onset (>60 years: 47 patients) and younger-onset (≤60 years: 95 patients) groups according to their age at diagnosis of AOSD. Clinical features, treatments, and prognosis were compared between the elderly-onset and younger-onset groups. RESULTS: In the elderly-onset group, compared with the younger-onset group, typical skin rashes were less frequent (21.3% vs 58.9%, respectively; p < .0001), whereas pleuritis (27.7% vs 7.4%, respectively; p = .0011) and disseminated intravascular coagulation (19.1% vs 2.1%, respectively; p = .0004) were more frequent, and serum ferritin levels were higher (median 12,700 ng/ml vs 2526 ng/ml, respectively; p < .0001). Overall survival and AOSD-related survival were reduced (p = .0006 and p = .0023, respectively) and drug-free remission was less frequent (p = .0035) in the elderly-onset group compared with the younger-onset group. CONCLUSIONS: Our results demonstrated that elderly-onset AOSD patients had several characteristics that differed from younger-onset AOSD patients, including less typical skin lesions, more AOSD-related complications, higher ferritin levels, and poorer prognoses.

Rituximab maintenance therapy for patients with antineutrophil cytoplasmic antibody-associated vasculitis in Japan.

OBJECTIVES: We examined the efficacy and safety of rituximab (RTX) maintenance therapy for patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in Japan. METHODS: We conducted a retrospective study using a multi-center cohort database of vasculitis patients. All maintenance treatment courses were divided into three groups: a RTX group, a group treated with other immunosuppressant drugs (IS) and a group receiving glucocorticoid monotherapy (GC). The primary endpoint was the comparison of relapse-free survival after 1 year. We also analyzed the occurrence of severe adverse events (SAEs) to assess safety. RESULTS: We included 123 courses of 107 patients (RTX n = 14, IS n = 64, GC n = 45). Twelve of 14 in the RTX group patients were diagnosed with granulomatosis with polyangiitis (GPA). The relapse-free survival of RTX maintenance therapy was comparable to that in the other groups (p = .122). After 1 year of treatment, the RTX group was administered lower steroid doses and one-third of them could withdraw corticosteroid. The overall incidence of SAE was 0.54/patient-year in the RTX group, 0.39/patient-year in the IS group and 0.34/patient-year in the GC group. CONCLUSION: RTX maintenance therapy could be effective and safe in Japanese GPA patients.

Lacrimal drainage function after cheese wiring of lacrimal passage intubation.

PURPOSE: To investigate how cheese wiring affects lacrimal drainage function by quantitative assessment of tear function and punctal dimensions. METHODS: Patients who underwent lacrimal passage intubation between January 2017 and September 2018 were enrolled prospectively. Among these patients, those with postoperative cheese wiring who received lacrimal passage intubation in one eye met the criteria for further investigation. The subjective symptoms of epiphora, dimensions of puncta, lower tear meniscus, and tear clearance were assessed postoperatively in both the involved eye and untreated contralateral eye. Punctum dimensions were analysed using the digital slit-lamp image. Tear meniscus and tear clearance were assessed by anterior segment optical coherence tomography. RESULTS: Postoperative cheese wiring was observed in 68 of 314 eyes. Among these cases, 36 patients (age 70.5 ± 11.7 years) had cheese wiring only in one eye: with the involvement of both puncta in 15 patients (group A) and only the lower punctum in 21 patients (group B). There was no patient with the involvement of only the upper punctum. While tear function of the involved eyes in group B did not differ from that of the untreated eye, it was significantly decreased in group A compared with that in untreated control eyes (p < 0.05). The tear clearance rate correlated significantly with the upper punctum dimensions (p < 0.05), but not with the lower punctum. CONCLUSION: Analysis of cheese wiring after lacrimal passage intubation with tear function demonstrated that the integrity of the puncta and the canaliculus is important for lacrimal drainage.

ADVERSE EFFECT OF MACULAR INTRARETINAL HEMORRHAGE ON THE PROGNOSIS OF SUBMACULAR HEMORRHAGE DUE TO RETINAL ARTERIAL MACROANEURYSM RUPTURE.

PURPOSE: To investigate the clinical course of submacular hemorrhage associated with ruptured retinal arterial macroaneurysm using swept-source optical coherence tomography. METHODS: This study included 23 eyes of 23 consecutive patients diagnosed with submacular hemorrhage associated with ruptured retinal arterial macroaneurysm. Cases underwent displacement of submacular hemorrhage (vitrectomy + subretinal injection of tissue plasminogen activator + air tamponade) and were followed up for 6 months after surgery. Localization of the preoperative hemorrhage and its effect on preoperative and postoperative best-corrected visual acuity, central retinal thickness, and continuity of the ellipsoid zone were measured. RESULTS: Macular intraretinal hemorrhage (IRH) was observed in 17 eyes (73.9%, IRH [+] group) and was not observed in 6 eyes (26.1%, IRH [-] group). The IRH (+) group showed worse postoperative best-corrected visual acuity values compared with the IRH (-) group (0.89 ± 0.47 in logarithm of the minimal angle of resolution units, Snellen equivalent 20/155 and 0.16 ± 0.23, 20/29, respectively; P < 0.01), smaller central retinal thickness values (97.7 ± 53.5 µm, 173.0 ± 32.3 µm, respectively; P < 0.01), and a higher rate of ellipsoid zone disruption (100%, 33.3%, respectively; P < 0.01). CONCLUSION: Patients with preoperative macular IRH showed lower postoperative visual acuity and worse macular contour after submacular hemorrhage displacement compared with patients without macular IRH.

Prospective assessment of plate-haptic rotationally asymmetric multifocal toric intraocular lens with near addition of + 1.5 diopters.

BACKGROUND: To prospectively evaluate surgical results following implantation of rotationally asymmetric, plate-haptic, refractive segmented multifocal toric intraocular lenses (IOLs) with near addition of + 1.5 diopters (D) (Lentis Comfort LS-313 MF15T, Oculentis GmbH). METHODS: In 59 eyes of 41 patients, ocular examinations were conducted before and 1 day, 1 week, 1, 3, and 6 months after surgery. Uncorrected (UDVA) and corrected (CDVA) distance visual acuity, uncorrected (UIVA) and distance-corrected (DCIVA) intermediate visual acuity at 70 cm, and uncorrected (UNVA) and distance-corrected (DCNVA) near visual acuity at 30 cm were tested. A defocus curve was drawn, and the degree of disturbing photic phenomena were questioned. RESULTS: The IOL showed excellent rotational stability; the average absolute rotation was 1.66 ± 1.17 degrees from 1 day 1 to 6 months postoperatively, and 98.1 and 100% of eyes yielded rotation of less than 5 and 10 degrees, respectively. Postoperative distance and intermediate visual acuity were highly satisfactory; UDVA, CDVA, UIVA, and DCIVA were about 20/20, 20/16, 20/25, 20/25, respectively. Near visual acuity was suboptimal; UNVA and DCNVA were at approximately 20/60. The defocus curve analysis showed that 20/25 and 20/40 uncorrected visual acuity was attained at as close as 60 and 40 cm, respectively. Contrast sensitivity was within a normal range, and subjective photic phenomena were minimum. CONCLUSIONS: The refractive segmented, rotationally asymmetric multifocal toric IOLs with + 1.5 D near addition showed superb rotational stability and highly satisfactory distance and intermediate vision. Contrast sensitivity was high and incidence of photic symptoms was very low. TRIAL REGISTRATION: This study was registered at JAPIC Clinical Trials Information, ID: JapicCTI-183,877, https://www.clinicaltrials.jp/cti-user/trial/Search.jsp (February 5, 2018).

Evaluation of time courses of agreement between minutely obtained transcutaneous blood gas data and the gold standard arterial data from spontaneously breathing Asian adults, and various subgroup analyses.

BACKGROUND: Usual clinical practice for arterial blood gas analysis (BGA) in conscious patients involves a one-time arterial puncture to be performed after a resting period of 20-30 min. The aim of this study was to evaluate the use of transcutaneous BGA for estimating this gold standard arterial BGA. METHODS: Spontaneously breathing Asian adults (healthy volunteers and respiratory patients) were enrolled (n = 295). Transcutaneous PO2 (PtcO2) and PCO2 (PtcCO2) were monitored using a transcutaneous monitor (TCM4, Radiometer Medical AsP, Denmark) with sensors placed on the chest, forearm, earlobe or forehead. Transcutaneous BGA at 1-min intervals was compared with arterial BGA at 30 min. Reasonable steps to find severe hypercapnia with PaCO2 > 50 mmHg were evaluated. RESULTS: Sensors on the chest and forearm were equally preferred and used because of small biases (n = 272). The average PCO2 bias was close to 0 mmHg at 4 min, and was almost constant (4-5 mmHg) with PtcCO2 being higher than PaCO2 at ≥8 min. The limit of agreement for PCO2 narrowed over time: ± 13.6 mmHg at 4 min, ± 7.5 mmHg at 12-13 min, and ± 6.3 mmHg at 30 min. The limit of agreement for PO2 also narrowed over time (± 23.1 mmHg at 30 min). Subgroup analyses showed that the PaCO2 and PaO2 levels, gender, and younger age significantly affected the biases. All hypercapnia subjects with PaCO2 > 50 mmHg (n = 13) showed PtcCO2 ≥ 50 mmHg for until 12 min. CONCLUSIONS: Although PtcCO2 is useful, it cannot completely replace PaCO2 because PCO2 occasionally showed large bias. On the other hand, the prediction of PaO2 using PtcO2 was unrealistic in Asian adults. PtcCO2 ≥ 50 mmHg for until 12 min can be used as a screening tool for severe hypercapnia with PaCO2 > 50 mmHg.

Schnitzler's syndrome: A female elderly case presenting intractable non-pruritic febrile urticarial rush.

Schnitzler's syndrome is an acquired autoinflammatory disease characterized by chronic urticarial rash and monoclonal gammopathy (predominantly IgM type). A 75-year-old Japanese woman complained of high fever and non-pruritic urticarial rash appearing almost every day for 3 years. Her abnormal laboratory data included leukocytosis and neutrophilia with elevated erythrocyte sedimentation rate and C-reactive protein level. Hyperglobulinemia of IgA and IgM was also noted. Histological analysis revealed perivascular and interstitial neutrophilic infiltration without any signs of vasculitis. Immunofixation analysis confirmed IgM-kappa-type monoclonal gammopathy. Oral prednisolone initially improved her symptoms, but recurrence was observed upon its tapering. The addition of colchicine successfully controlled her symptoms and allowed a reduction in the dose of systemic steroid.

Suppression of joint destruction with subcutaneous tocilizumab for Japanese patients with rheumatoid arthritis in clinical practice.

Objectives: To investigate the efficacy of suppressing joint destruction with subcutaneous tocilizumab (TCZ-SC) for Japanese rheumatoid arthritis (RA) patients in the real-world clinical setting.Methods: This 1-year prospective, multicenter study included 110 RA patients in whom TCZ-SC was newly initiated. Primary endpoint was the change from baseline in vdH-modified total Sharp score (mTSS) at week 52. Structural remission was defined as yearly mTSS of 0.5 or less. Disease activity was evaluated using the disease activity score (DAS28-ESR) and clinical disease activity index (CDAI).Results: At baseline, the patients' mean age was 58.6 years, and the mean disease duration was 10.6 years. The proportion of patients who were naïve for biologics was 44.5%, and 64.5% concomitantly received methotrexate. The yearly mTSS showed significant improvement from 9.41 before TCZ-SC initiation to -0.15 after 52 weeks. The structural remission rate was 76.1%. After 52 weeks, the DAS28-ESR and CDAI remission rates were 52% and 21%, respectively. Although the previous usage of biologics and baseline disease activity significantly affected the clinical remission, no factors with significant effects on structural remission were identified.Conclusion: These findings support the efficacy of TCZ-SC in suppressing disease activity as well as joint destruction over a 1-year period.

Results of lamellar macular hole-associated epiretinal proliferation embedding technique for the treatment of degenerative lamellar macular hole.

PURPOSE: To investigate the outcomes of embedding lamellar hole-associated epiretinal proliferation (LHEP) into retinal cleavage for the surgical treatment of degenerative lamellar macular hole (LMH). METHODS: We retrospectively reviewed the medical records of 34 consecutive eyes of degenerative LMH patients who underwent vitrectomy with LHEP embedding and who were followed up for at least 12 months. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), and macular structure preoperatively and at the final follow-up were compared. RESULTS: The mean (±SD) follow-up period was 30.0 ± 17.7 months. Twelve patients (35.3%) were men, and the mean age was 69.6 ± 10.1 years. Twenty-three eyes (67.6%) underwent simultaneous cataract surgery. BCVA was significantly improved at the final visit, from 0.31 ± 0.25 logarithm of the minimum angle of resolution units to 0.10 ± 0.25 (P < 0.01). This improvement in mean BCVA at the final postoperative visit occurred regardless of whether the eyes underwent simultaneous cataract surgery, from 0.30 ± 0.26 preoperatively to 0.04 ± 0.16 (P < 0.01) in the "with cataract surgery" group and from 0.32 ± 0.26 preoperatively to 0.21 ± 0.35 (P < 0.05) in the "without cataract surgery" group. CRT was also significantly improved at the final visit, from 123.2 ± 42.6 µm preoperatively to 191.2 ± 42.6 µm (P < 0.01). External limiting membrane and ellipsoid zone defects were detected in 17 (50.0%) and 15 (44.1%) eyes, respectively, but these were resolved in 10 (58.8%) and 7 (46.7%) eyes, respectively, at the final visit. No intraoperative or postoperative complications were observed. CONCLUSIONS: Embedding LHEP may be an effective and safe procedure to treat degenerative LMH.

Incidence and Outcomes of Repositioning Surgery to Correct Misalignment of Toric Intraocular Lenses.

PURPOSE: To analyze the incidence and appropriate timing of repositioning surgery to correct misalignment of acrylic foldable toric intraocular lenses (IOLs). DESIGN: Retrospective, multicenter case series. PARTICIPANTS: Patients who had undergone phacoemulsification and implantation of toric IOL at 8 surgical sites. METHODS: Patient charts were reviewed to collect data on repositioning surgery of toric IOLs. MAIN OUTCOME MEASURES: Incidence, timing, and outcomes of repositioning surgery. RESULTS: Among 6431 eyes implanted with toric IOLs, 42 eyes (0.653%) of 42 patients underwent repositioning surgery at an average of 9.9±7.5 days (range, 0-30 days) after IOL implantation. The repositioning surgery significantly reduced misalignment from 32.9°±15.7° to 8.8°±9.7° (P < 0.001), which was measured at 7.6±5.0 weeks postoperatively. Refractive cylinder was significantly reduced from 2.4±1.1 diopters (D) to 1.1±0.8 D (P < 0.001). There was a significant negative correlation between the interval from cataract surgery to repositioning procedure and the degree of residual misalignment (r = -0.439, P < 0.001). The residual misalignment was 13.1°±13.5° when the repositioning surgery was performed within 6 days after cataract surgery, whereas the residual misalignment was 6.3°±5.9° when the IOL was repositioned 7 days or later (P < 0.001). In 2 eyes that were treated within 24 hours after cataract surgery, the IOL re-rotated significantly, and additional surgical intervention was required. CONCLUSIONS: Toric IOLs were repositioned in 0.653% of cases. A relationship was found between the timing of repositioning surgery and surgical outcome. These data suggest that repositioning surgery should be performed 1 week after IOL implantation.

High-dose prednisolone after intravenous methylprednisolone improves prognosis of acute exacerbation in idiopathic interstitial pneumonias.

BACKGROUND AND OBJECTIVE: Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) (AE-IPF) is a poor prognostic disorder. AE is also reported to occur in other idiopathic interstitial pneumonias (IIPs). There are limited data available regarding the effectiveness of treatment for AE-IIPs. The objective of this study was to clarify the prognostic impact of the initial dose of prednisolone (PSL) for treating AE-IIPs. METHODS: Eighty-five patients with AE-IIPs, diagnosed according to the criteria of the Japanese Respiratory Society, were enrolled in this study (IPF/non-IPF: 63/22 patients) from 2004 to 2013. We performed multivariate Cox proportional hazard regression analysis to identify poor prognostic factors. HRCT patterns at the onset of AE-IIPs were classified as diffuse or non-diffuse. We evaluated the prognostic significance of the initial dose of PSL by adjusting for other prognostic factors. RESULTS: Median survival time (MST) after AE-IIPs diagnosis was 49 days. MST of AE-IPF and AE-non-IPF was 39 and 49 days, respectively. A diffuse HRCT pattern, lower serum IgG and higher serum surfactant protein-D at AE diagnosis, long-term oxygen therapy (LTOT) before AE and positive pressure ventilation (PPV) use for AE were significant poor prognostic factors for all patients, as were LTOT before AE and lower serum IgG for no-PPV patients. High-dose PSL ≥ 0.6 mg/kg was a significant prognostic factor for no-PPV patients after adjusting for other prognostic factors. CONCLUSION: We concluded that a dose of PSL ≥ 0.6 mg/kg after i.v. high-dose methylprednisolone therapy should be recommended for the treatment of AE-IIPs.

Impact of methotrexate dose on efficacy of adalimumab in Japanese patients with rheumatoid arthritis: Results from registered data analyses.

OBJECTIVE: Upper limit of methotrexate (MTX) for patients with rheumatoid arthritis (RA) was recently increased from 8 to 16 mg/week in Japan. We therefore examined the effect of concomitant MTX dose on the efficacy of adalimumab (ADA) in clinical practice. METHOD: Sixty-one consecutive RA patients treated with ADA were followed for minimum 52 weeks and retrospectively compared by MTX dose; patients receiving concomitant MTX of 10 mg/week or more (MTX ≥10 mg group) and <10 mg/week (MTX <10 mg group). Disease activity and remission were evaluated by the disease activity score 28 (DAS28) criteria. RESULTS: The MTX ≥10 mg group consistently showed better improvement in DAS28 and resulted in more patients (52.8%) with DAS28-remission compared with the MTX <10 mg group (26.1%). Multivariate analysis showed that MTX ≥10 mg had a significant effect on DAS28 remission with odds ratio of 5.12. ADA retention rate was 72.2% in MTX ≥10 mg group compared with 52.0% in MTX <10 mg group. Discontinuation of ADA due to adverse events were comparable in the MTX ≥10 mg and MTX <10 mg groups (11.1% vs. 12.0%). CONCLUSIONS: These findings support the critical role of concomitant MTX in the efficacy of ADA, and recommend use of MTX ≥10 mg in Japanese RA patients.

Clinical outcome of urachal cancer in Japanese patients.

BACKGROUND: The outcome of treatment of Japanese patients with urachal cancer is not well known. The purpose of this study is to clarify the characteristics and outcomes of Japanese patients with urachal cancer. MATERIALS AND METHODS: The medical records of patients with urachal cancer who were treated in our hospital between 1994 and 2014 were retrospectively reviewed and statistically analyzed. RESULTS: We found 28 patients who had been diagnosed with urachal cancer and treated in our hospital during the study period. The median age of these patients was 52.3 years [interquartile range (IQR), 46.0-56.8 years]. Seventeen patients underwent surgery in our department. The median observation period of these patients was 42.6 months (IQR, 21.1-49.7 months). Among patients who had undergone surgery, cancer recurred in 7 (41 %). The estimated median time from surgery to recurrence and overall survival (OS) period were 35.8 months [95 % confidence interval (CI), 7.7 months-not determined] and not reached, respectively. Seventeen patients received chemotherapy for metastatic disease. The estimated median OS time from initial metastasis was 23.5 months (95 % CI, 11.8-33.3 months). CONCLUSIONS: Urachal cancer is usually locally advanced at presentation and it has a high risk of distant metastases. However, long-term survival following surgical treatment occurs in a significant fraction of patients. This study indicates the current treatment results for patients with urachal cancer in Japanese clinical practice. To establish a standard operation method and chemotherapy, a multicenter, prospective study is needed in a larger population in the future.

Magnetic resonance enterocolonography in detecting erosion and redness in intestinal mucosa of patients with Crohn's disease.

BACKGROUND AND AIM: In Crohn's disease (CD), assessment of disease activity and extension is important for clinical management. Endoscopy is the most reliable tool for evaluating disease activity in these patients and it distinguishes between lesions based on ulcer, erosion, and redness. Magnetic resonance imaging (MRI) is less invasive than endoscopy; however, the sensitivity of MRI in detecting lesions is believed to be lower, and whether MRI can detect milder lesions has not been studied. The aim of this study was to compare the detection ability of magnetic resonance enterocolonography (MREC) with ileocolonic endoscopy in patients with CD. METHODS: A total of 27 patients with CD underwent both MREC and ileocolonoscopy. There were 55 lesions (18 ileum and 37 colon) endoscopically detected, and the findings of MREC were compared with each ileocolonoscopic finding to determine sensitivity and specificity. RESULTS: For a positive lesion defined as having at least one of the following: wall thickness, edema, diffusion-weighted imaging (DWI) high intensity and relative contrast enhancement (RCE) on MREC, the sensitivities were 100% for ulcer, 84.6% for erosion, and 52.9% for redness, suggesting an ability to detect milder lesions such as erosion or redness. Moreover, RCE values were well correlated with the severity of endoscopically identified active lesions. CONCLUSION: MREC findings may be useful not only for evaluation of ulcers, but also for detection of endoscopically identified milder lesions in CD, suggesting a clinical usefulness of MREC for disease detection and monitoring.

Clinical response to induction chemotherapy predicts improved survival outcome in urothelial carcinoma with clinical lymph nodal metastasis treated by consolidative surgery.

BACKGROUND: To determine the indications for post-chemotherapy consolidative surgery in patients with clinical lymph node (LN) metastatic (cN+) urothelial carcinoma (UC). METHODS: Sixty UC patients with measurable cN+ but without detectable systemic visceral/bone dissemination received induction platinum-based chemotherapy. Consolidative surgery was offered to all patients except for those with progressive disease. We retrospectively analyzed the clinicopathological response to induction chemotherapy and identified prognostic factors for overall survival (OS). RESULTS: The primary cancer site was the urinary bladder in 31 patients (52 %) and upper urinary tract in 29 (48 %). The median number of chemotherapy courses was 4. Forty-five patients (75 %) showed a clinically objective response to the induction chemotherapy. Fifty-one patients (85 %) underwent subsequent consolidative surgery. Histopathological analysis indicated pT0 status in 10 (20 %) and pN0 in 17 (33 %). When all 60 patients were considered, clinical tumor response was found to be significantly correlated with achievement of pathological complete response. At the median follow-up of 22 months, the median progression-free survival and OS periods were excellent: 18.6 and 31.6 months, respectively. In the multivariate analysis, clinical tumor response was found to be an independent pre-surgical prognostic factor for OS, and pathologically negative lymph node, negative resection margin, more LNs removed, and negative lymphovascular invasion were found to be independent post-surgical prognostic parameters for OS. CONCLUSIONS: The median OS in induction chemotherapy followed by consolidative surgery was very encouraging. Our results suggest that achieving a good clinical response to pre-surgical induction chemotherapy is a good indication for subsequent consolidative surgery in UC patients with cN+ to improve OS through a good pathological response.

CIN85 is required for Cbl-mediated regulation of antigen receptor signaling in human B cells.

The aberrant regulation of B-cell receptor (BCR) signaling allows unwanted B cells to persist, thereby potentially leading to autoimmunity and B-cell malignancies. Casitas B-lineage lymphoma (Cbl) proteins suppress BCR signaling; however, the molecular mechanisms that control Cbl function in human B cells remain unclear. Here, we demonstrate that CIN85 (c-Cbl interacting protein of 85 kDa) is constitutively associated with c-Cbl, Cbl-b, and B-cell linker in B cells. Experiments using CIN85-overexpressing and CIN85-knockdown B-cell lines revealed that CIN85 increased c-Cbl phosphorylation and inhibited BCR-induced calcium flux and phosphorylation of Syk and PLCγ2, whereas it did not affect BCR internalization. The Syk phosphorylation in CIN85-overexpressing and CIN85-knockdown cells was inversely correlated with the ubiquitination and degradation of Syk. Moreover, CIN85 knockdown in primary B cells enhanced BCR-induced survival and growth, and increased the expression of BcLxL, A1, cyclin D2, and myc. Following the stimulation of BCR and Toll-like receptor 9, B-cell differentiation- associated molecules were up-regulated in CIN85-knockdown cells. Together, these results suggest that CIN85 is required for Cbl-mediated regulation of BCR signaling and for downstream events such as survival, growth, and differentiation of human B cells.