Effect of ipragliflozin on liver function in Japanese type 2 diabetes mellitus patients: subgroup analysis of a 3-year post-marketing surveillance study (STELLA-LONG TERM).

The STELLA-LONG TERM prospective post-marketing surveillance study assessed ipragliflozin in Japanese patients with type 2 diabetes mellitus (T2DM). This subgroup analysis of patients with liver impairment used the final 3-year results. Data on patients, adverse drug reactions (ADRs), and changes in glycemic parameters and liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], gamma-glutamyl transpeptidase [γ-GTP] and alkaline phosphatase [ALP]) were collected, and the fatty liver index (FLI) was calculated. In the effectiveness analysis (n = 8,763), baseline liver function was normal in 2,605 patients (ALT <31/<21 U/L [men/women]) and abnormal in 3,277 (ALT ≥31/≥21 U/L). The abnormal liver function group had higher mean body weight and BMI than the normal liver function group (p < 0.001). In the safety analysis (n = 11,051), urinary tract infections, genital infections and hepatic disorders were more common in the abnormal than normal liver function group (2.25% vs. 1.07%; 1.78% vs. 1.14% and 1.85% vs. 1.01%). In the abnormal liver function group, there were significant (p < 0.001) decreases from baseline at 36 months in AST and ALT (from 38.8 and 53.7 U/L to 29.3 and 37.7 U/L, respectively), γ-GTP (from 75.4 to 51.7 U/L) and ALP (from 254.8 to 234.5 U/L), which were greater than in the normal liver function group. FLI reductions at 36 months were significant (p < 0.001) in subgroups with baseline FLI of ≥30 or ≥60. In conclusion, ipragliflozin improved liver function over 3 years in patients with impaired liver function, although ADRs occurred more frequently than in the normal liver function group.

Kif1c regulates osteoclastic bone resorption as a downstream molecule of p130Cas.

Podosome formation in osteoclasts is an important initial step in osteoclastic bone resorption. Mice lacking c-Src (c-Src-/- ) exhibited osteopetrosis due to a lack of podosome formation in osteoclasts. We previously identified p130Cas (Crk-associated substrate [Cas]) as one of c-Src downstream molecule and osteoclast-specific p130Cas-deficient (p130CasΔOCL-/- ) mice also exhibited a similar phenotype to c-Src-/- mice, indicating that the c-Src/p130Cas plays an important role for bone resorption by osteoclasts. In this study, we performed a cDNA microarray and compared the gene profiles of osteoclasts from c-Src-/- or p130CasΔOCL-/- mice with wild-type (WT) osteoclasts to identify downstream molecules of c-Src/p130Cas involved in bone resorption. Among several genes that were commonly downregulated in both c-Src-/- and p130CasΔOCL-/- osteoclasts, we identified kinesin family protein 1c (Kif1c), which regulates the cytoskeletal organization. Reduced Kif1c expression was observed in both c-Src-/- and p130CasΔOCL-/- osteoclasts compared with WT osteoclasts. Kif1c exhibited a broad tissue distribution, including osteoclasts. Knockdown of Kif1c expression using shRNAs in WT osteoclasts suppressed actin ring formation. Kif1c overexpression restored bone resorption subsequent to actin ring formation in p130CasΔOCL-/- osteoclasts but not c-Src-/- osteoclasts, suggesting that Kif1c regulates osteoclastic bone resorption in the downstream of p130Cas (191 words). SIGNIFICANCE OF THE STUDY: We previously showed that the c-Src/p130Cas (Cas) plays an important role for bone resorption by osteoclasts. In this study, we identified kinesin family protein 1c (Kif1c), which regulates the cytoskeletal organization, as a downstream molecule of c-Src/p130Cas axis, using cDNA microarray. Knockdown of Kif1c expression using shRNAs in wild-type osteoclasts suppressed actin ring formation. Kif1c overexpression restored bone resorption subsequent to actin ring formation in osteoclast-specific p130Cas-deficient (p130CasΔOCL-/- ) osteoclasts but not c-Src-/- osteoclasts, suggesting that Kif1c regulates osteoclastic bone resorption in the downstream of p130Cas.

Comparison of the Perioperative and Postoperative Outcomes of Ileal Conduit and Cutaneous Ureterostomy: A Propensity Score-Matched Analysis.

INTRODUCTION: To compare perioperative and postoperative outcomes related to urinary diversion (UD) between ileal conduit and cutaneous ureterostomy following open radical cystectomy (ORC). METHODS: This retrospective study included 232 patients with bladder cancer who underwent ORC and subsequent UD (ileal conduit, n = 123; cutaneous ureterostomy, n = 109) at Kobe University and related hospitals between January 2007 and December 2016. A propensity score method was used to adjust the preoperative status of the two groups, and the perioperative and postoperative outcomes were compared between matched cohorts. In addition, we evaluated several factors predicting renal deterioration. RESULTS: In the matched cohorts, 87 patients were included in each group. While the operative time and postoperative fasting periods were significantly longer in patients with ileal conduit in comparison to those with cutaneous ureterostomy (both p < 0.001), there were no differences in blood loss or duration of hospitalization. Although the incidence of grade ≥III perioperative complications was similar between the two groups, the incidence of postoperative recurrent pyelonephritis in the cutaneous ureterostomy group was significantly higher than that in the ileal conduit group (25.3 and 11.4%, respectively; p = 0.030), and cutaneous ureterostomy was identified as a significant predictor of a decrease in the estimated glomerular filtration rate with an odds ratio of 2.13 (95% confidence interval, 1.19-3.85; p = 0.010). CONCLUSIONS: The perioperative safety of ileal conduit was comparable to that of cutaneous ureterostomy, and cutaneous ureterostomy was a significant risk factor for pyelonephritis and subsequent renal deterioration, suggesting that ileal conduit may be preferable to cutaneous ureterostomy.

External validation of nomograms for prediction of progression-free survival and liver toxicity in patients with advanced renal cell carcinoma treated with pazopanib.

BACKGROUND: Nomograms have been developed for the prediction of progression-free survival (PFS) and liver toxicity in patients with advanced renal cell carcinoma (RCC) who are treated with pazopanib. The objectives of this study were to review clinical outcomes, to perform an external validation of these nomograms and to develop a new nomogram in Japanese patients. METHODS: A retrospective chart review of 150 Japanese patients with advanced RCC who received pazopanib at Kobe University Hospital and affiliated hospitals from March 2014 to June 2017 was performed. We evaluated the clinical efficacy and safety of pazopanib using logistic regression analysis to analyze the prognostic factors for overall survival (OS) and PFS. For nomogram validation, concordance index (C-index) and calibration were used. RESULTS: The median PFS and OS in this study was 13.1 and 37.4 months, respectively. Multivariate analyses identified prognostic factors for OS (number of metastasis, white blood cell (WBC) count and lactate dehydrogenase) and PFS (number of metastasis, WBC count). The C-index of nomograms for 12-month PFS was 0.598. The C-index of nomograms for liver toxicity was 0.558. A new Nomogram for predicting 12-month PFS for patients who received pazopanib was developed and performed internal validation. The C-index of the nomogram was 0.768. CONCLUSION: The clinical effect and safety of pazopanib reported in this study was similar to previous studies. This study suggests careful application of nomograms to Japanese patients treated with pazopanib. We have developed a new nomogram for predicting 12-month PFS with pazopanib therapy from Japanese patients.

Effect of ipragliflozin on liver function in Japanese type 2 diabetes mellitus patients: a subgroup analysis of the STELLA-LONG TERM study (3-month interim results).

This subgroup analysis of STELLA-LONG TERM, an ongoing 3-year post-marketing surveillance study on the long-term efficacy and safety of ipragliflozin, assessed the effect of ipragliflozin on liver function in type 2 diabetes mellitus (T2DM) patients. Patients were divided according to baseline liver function (normal [male: ALT ≤30, female: ALT ≤20], abnormal [male: ALT ≥31, female: ALT ≥21]). We evaluated changes in aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (γ-GTP), alkaline phosphatase (ALP), and fatty liver index (FLI) at 3 months of treatment; the proportion of patients with abnormal liver function whose liver function normalized after 3 months of treatment; and correlations between changes in ALT levels and efficacy variables/laboratory values. Liver function was normal in 2,570 and abnormal in 3,239 patients. Only patients with abnormal liver function showed a statistically/clinically significant decrease in AST, ALT, γ-GTP, and ALP levels at 3 months (all p < 0.05 vs. baseline). The FLI significantly decreased from 63.2677 ± 26.4363 (baseline) to 56.7137 ± 27.6484 (3 months) (p < 0.05) in the overall patient population. Liver function normalized in 20.5% (543/2,648) of patients with abnormal liver function. There was no obvious correlation between changes in ALT and changes in efficacy/laboratory parameters. Liver function improved after 3-month treatment with ipragliflozin in T2DM patients with abnormal liver function.

Improved cardiometabolic risk factors in Japanese patients with type 2 diabetes treated with ipragliflozin: a pooled analysis of six randomized, placebo-controlled trials.

To examine differential improvements among cardiovascular risk factors in response to treatment with ipragliflozin in Japanese type 2 diabetes mellitus (T2DM) patients, we conducted a pooled analysis of six randomized, double-blind trials of Japanese T2DM patients who received ipragliflozin 50 mg/day or placebo and had patient-level data for cardiometabolic risk parameters. Risk factors included glycated hemoglobin (HbA1c), body weight, homeostatic model assessment for insulin resistance and beta-cell function (HOMA-R and HOMA-beta, respectively), systolic blood pressure, fasting serum insulin concentrations, and the concentration of uric acid, lipids, and liver enzymes from baseline to end of treatment (EOT; 12-24 weeks). The primary endpoint of each trial was the change in HbA1c from baseline to EOT. Changes in risk factors from baseline to EOT were compared between ipragliflozin-treated and placebo groups, and between two subgroups (high- and low-risk groups for each parameter). All parameters, except low-density lipoprotein cholesterol (LDL-C) and non high-density lipoprotein cholesterol (non HDL-C), improved significantly in the ipragliflozin group. Subgroup analysis revealed a significantly greater improvement in the high-risk group versus low-risk group in HbA1c, HOMA-R, HOMA-beta, aspartate transaminase, alanine transaminase, and gamma-glutamyltransferase, but not in any of the lipid parameters or blood pressure. Liver function improvement in the ipragliflozin group was significantly correlated with changes in body weight, HbA1c, HOMA-beta, and HOMA-R. This analysis demonstrated that, in Japanese T2DM patients, ipragliflozin 50 mg/day was associated with improvements in cardiometabolic risk factors, except for LDL-C and non HDL-C.

Trichosporon asteroides Isolated from Cutaneous Lesions of a Suspected Case of "paracoccidioidomycosis ceti" in a Bottlenose Dolphin (Tursiops truncatus).

"Paracoccidioidomycosis ceti" is a rare zoonotic fungal infection affecting dolphins and is endemic worldwide. The causative agents are Paracoccidioides species; however, it is impossible to isolate the fungal species. We isolated Trichosporon asteroides from multifocal, irregularly raised skin lesions on a female bottlenose dolphin (Tursiops truncatus) captured off coast of Japan, which was suspected to have "paracoccidioidomycosis ceti." An abundance of round, yeast-like cells was detected in a potassium hydroxide direct-mount specimen of the skin samples; however, nested PCR targeting the partial sequence of 43-kDa glycoprotein-coding gene correspondent to Paracoccidioides sp. was negative. Biopsied tissue samples were cultured on brain heart infusion agar plates supplemented with chloramphenicol, 1% yeast extract, and 4% sodium chloride (4% NaCl-BHI), on Mycosel agar with 4% sodium chloride (4% NaCl-Mycosel), and on potato dextrose agar supplemented with chloramphenicol (CPDA) at 35 °C for 4 weeks. Cream-colored and wrinkled colonies consisting of hyphae and arthroconidia grew on 4% NaCl-BHI and CPDA, while film-like colonies composed of arthroconidia and round yeast-like cells developed on 4% NaCl-Mycosel. Although these primary cultures resembled fresh isolates of P. brasiliensis, they were identified as Trichosporon asteroides based on routine mycological studies and the internal transcribed spacer regions of ribosomal RNA sequences. The results suggested that trichosporonosis caused by T. asteroides might remain latent among cases of "paracoccidioidomycosis ceti" diagnosed without cultures and molecular biological analysis.

Severe pes planovalgus successfully treated in a patient with mutilating rheumatoid arthritis using a new surgical approach involving medial malleolar resection and medial displacement of the talus: A case report.

We report the case of a 56-year-old female with mutilating rheumatoid arthritis, who developed severe pes planovalgus. The foot was successfully reconstructed through a combination of osteotomies, including medial displacement of the talus accompanied by resection of the medial malleolus. This maneuver enabled a ∼1-cm medial displacement of the hindfoot while minimizing the adverse effect on forefoot rotation.

Clinical features, outcomes, and survival factor in patients with vertebral osteomyelitis infected by methicillin-resistant staphylococci.

PURPOSE: To elucidate clinico-radiological features, therapeutic outcomes, and survival factors of vertebral osteomyelitis patients infected by methicillin-resistant staphylococci (MRS). METHODS: Vertebral osteomyelitis patients admitted to the orthopaedic department between 2007 and 2011 (n = 248) were selected for this multicenter study. We compared patients' backgrounds, therapeutic course, and in-hospital mortality between MRS and methicillin-susceptible staphylococci (MSS). We also examined survival factors of vertebral osteomyelitis due to MRS. RESULTS: Sixteen patients of MRS vertebral osteomyelitis and 55 patients of MSS were included in this study. In MRS vertebral osteomyelitis, the rates of comorbid diabetes mellitus, involvement of >2 vertebral bodies, in-hospital mortality, and operation of surgical debridement were higher compared to those in MSS vertebral osteomyelitis. Univariate analysis showed that operation of surgical debridement was a factor related to survival in MRS patients. CONCLUSIONS: Higher rate of comorbid diabetes mellitus, involvement of >2 vertebral bodies, in-hospital mortality, and performing surgical debridement are peculiar features of MRS vertebral osteomyelitis compared to MSS vertebral osteomyelitis. If patients with MRS vertebral osteomyelitis respond poorly to antibiotic therapy, it might be better to consider surgical debridement not to lose an opportunity of operation due to exacerbation of systemic conditions.

Radiologic Patterning of Hallux Deformity in Rheumatoid Arthritis and Its Relationship to Flatfoot.

Hallux deformities other than hallux valgus, especially those in the sagittal plane, have not yet been elucidated in the feet of patients with rheumatoid arthritis. The objectives of the present study were to classify rheumatoid arthritis hallux deformity in both the horizontal and the sagittal planes and investigate its relationship with flatfoot. Using a cross-sectional study design, we assessed patients with rheumatoid arthritis (527 feet in 274 patients) using radiographs and classified the deformity patterns of the great toes using cluster analysis. Of the 274 patients, the range of motion in the metatarsophalangeal joint was clinically investigated in 44 (16.1%) patients. The great toes could be divided into 5 clusters according to the characteristic configuration as follows: cluster I (normal type), cluster II (hallux valgus type), cluster III (boutonniere type), cluster IV (boutonniere with hallux valgus type), and cluster V (swan-neck type). Radiographic measurements revealed the characteristic deformities of each cluster, including splayed foot for cluster II; flat foot, metatarsal primus elevatus, and plantar displacement of the proximal phalanx for cluster III; and a mixture of these characteristics for cluster IV. Plantar displacement of the proximal phalanx, which was a specific characteristic of the boutonniere deformity, correlated significantly with the decreased dorsiflexion in the metatarsophalangeal joint. Our classification method revealed the relationship of hallux deformity in the sagittal plane to flatfoot and also demonstrated the usefulness of measuring basal phalanx displacement in predicting the range of motion of the metatarsophalangeal joint.

Seroepidemiological Prevalence of Multiple Species of Filoviruses in Fruit Bats (Eidolon helvum) Migrating in Africa.

Fruit bats are suspected to be a natural reservoir of filoviruses, including Ebola and Marburg viruses. Using an enzyme-linked immunosorbent assay based on the viral glycoprotein antigens, we detected filovirus-specific immunoglobulin G antibodies in 71 of 748 serum samples collected from migratory fruit bats (Eidolon helvum) in Zambia during 2006-2013. Although antibodies to African filoviruses (eg, Zaire ebolavirus) were most prevalent, some serum samples showed distinct specificity for Reston ebolavirus, which that has thus far been found only in Asia. Interestingly, the transition of filovirus species causing outbreaks in Central and West Africa during 2005-2014 seemed to be synchronized with the change of the serologically dominant virus species in these bats. These data suggest the introduction of multiple species of filoviruses in the migratory bat population and point to the need for continued surveillance of filovirus infection of wild animals in sub-Saharan Africa, including hitherto nonendemic countries.

Isolation and characterization of a novel alphaherpesvirus in fruit bats.

UNLABELLED: Bats are known to harbor emerging RNA viruses. Recent studies have used high-throughput sequencing technology to identify various virus species, including DNA viruses that are harbored by bats; however, little is known about the nature of these potentially novel viruses. Here, we report the characterization of a novel herpesvirus isolated from an Indonesian pteropodid bat. The virus, tentatively named fruit bat alphaherpesvirus 1 (FBAHV1), has a double-stranded DNA genome of 149,459 bp. The phylogenetic analyses suggested that FBAHV1 is phylogenetically grouped with simplexviruses within the subfamily Alphaherpesvirinae. Inoculation of FBAHV1 into laboratory mice caused a lethal infection. Virus infection was observed in lung, liver, and brain tissue. Serological and PCR screening revealed that fruit bats infected with FBAHV1 or its related virus are widely distributed in Indonesia. The identification of FBAHV1 makes a considerable contribution to our understanding of simplexviruses associated with bats. IMPORTANCE: Bats are known to harbor emerging viruses, such as lyssaviruses, henipaviruses, severe acute respiratory syndrome-like coronaviruses, and filoviruses. Although alphaherpesviruses are disseminated in humans and other animals, there is little information about their distribution in bats. Here, we isolated a previously unknown alphaherpesvirus from an Indonesian fruit bat. Genome sequence analysis suggested that the virus is a member of the genus Simplexvirus within the subfamily Alphaherpesvirinae, which also includes common human viruses, such as herpes simplex virus 1 and herpes simplex virus 2. FBAHV1 is the first bat-derived alphaherpesvirus whose complete genome has been sequenced.

Detection of novel polyomaviruses in fruit bats in Indonesia.

Bats are an important natural reservoir for a variety of viral pathogens, including polyomaviruses (PyVs). The aims of this study were: (i) to determine which PyVs are present in bats in Indonesia and (ii) to analyze the evolutionary relationships between bat PyVs and other known PyVs. Using broad-spectrum polymerase chain reaction (PCR)-based assays, we screened PyV DNA isolated from spleen samples from 82 wild fruit bats captured in Indonesia. Fragments of the PyV genome were detected in 10 of the 82 spleen samples screened, and eight full-length viral genome sequences were obtained using an inverse PCR method. A phylogenetic analysis of eight whole viral genome sequences showed that BatPyVs form two distinct genetic clusters within the proposed genus Orthopolyomavirus that are genetically different from previously described BatPyVs. Interestingly, one group of BatPyVs is genetically related to the primate PyVs, including human PyV9 and trichodysplasia spinulosa-associated PyV. This study has identified the presence of novel PyVs in fruit bats in Indonesia and provides genetic information about these BatPyVs.

Detection of coronavirus genomes in Moluccan naked-backed fruit bats in Indonesia.

Bats have been shown to serve as natural reservoirs for numerous emerging viruses including severe acute respiratory syndrome coronavirus (SARS-CoV). In the present study, we report the discovery of bat CoV genes in Indonesian Moluccan naked-backed fruit bats (Dobsonia moluccensis). A partial RNA-dependent RNA polymerase gene sequence was detected in feces and tissues samples from the fruit bats, and the region between the RdRp and helicase genes could also be amplified from fecal samples. Phylogenetic analysis suggested that these bat CoVs are related to members of the genus Betacoronavirus.

Japanese nationwide surveillance in 2011 of antibacterial susceptibility patterns of clinical isolates from complicated urinary tract infection cases.

To investigate antimicrobial susceptibility patterns of various bacterial pathogens isolated from complicated urinary tract infection (UTI) cases, the Japanese Society of Chemotherapy, the Japanese Association of Infectious Disease, and the Japanese Society of Clinical Microbiology conducted the second nationwide surveillance from January to September 2011. With the cooperation of 42 medical institutions throughout Japan, 1036 strains belonging to 8 clinically relevant bacterial species were collected. Among methicillin-resistant Staphylococcus aureus (MRSA) strain, the vancomycin (VCM) MIC for 5.5% (3/55) of the strains was 2 µg/mL. Ampicillin, VCM, and linezolid were relatively active against 209 Enterococcus faecalis strains. The proportion of fluoroquinolone (FQ)-resistant strains was >20%. The MIC90 of FQs against the 382 Escherichia coli strains was 2-64 mg/L and the proportion resistant to FQs was approximately 30%. However, susceptibility of E. coli to sitafloxacin was still high (MIC90 = 2 mg/L). Fifty-eight (15.2%) of 382 E. coli, 6 (4.5%) of 132 Klebsiella pneumoniae, 1 (2.4%) of 41 Klebsiella oxytoca and 4 (6.8%) of 59 Proteus mirabilis strains were suspected of producing extended-spectrum beta-lactamase. Of 93 Pseudomonas aeruginosa strains, the proportions resistant to imipenem, amikacin, and ciprofloxacin were 21.5%, 4.3%, and 20.4%, respectively. Four strains (4.3%) were found to be multidrug-resistant. In complicated UTI cases, all of MRSA and E. faecalis were susceptible to all anti-MRSA agents. Sitafloxacin was active against other FQ-resistant E. coli strains. The isolation of extended-spectrum beta-lactamase-producing and multidrug-resistant strains increased.

Partial transmalleolar approach for lateral impingement after total ankle arthroplasty: a case report.

Advances in implant technology have made total ankle arthroplasty an increasingly popular alternative to arthrodesis for the management of ankle arthritis. However, a frequent complication of the procedure is nerve impingement related to either to heterotrophic bone growth or the prosthesis itself. Successful resolution of this complication presents a challenge to clinicians. We present a case of lateral impingement following total ankle arthroplasty that was successfully treated using a partial transmalleolar approach to effect a partial osteotomy of the lateral malleolus and create a fragment attached to the anterior talofibular and calcaneofibular ligaments. This approach provides a good operative field in the lateral gutter with minimal soft tissue impairment. It also facilitates curettage, and resolution of tissue impingement. The osteotomy site healed fully by 3 months postoperative, and the pain around the lateral malleolus resolved. Furthermore, the patient's score on the Japanese Society for Surgery of the Foot Ankle/Hindfoot Scale improved from 33 preoperatively to 82 at 6 months postoperative.

Correlation between knee and hindfoot alignment in patients with rheumatoid arthritis: The effects of subtalar joint destruction.

OBJECTIVES: Compensatory hindfoot alignment for deformities at the knee level has been demonstrated in patients with knee osteoarthritis. However, this phenomenon has not been elucidated in patients with rheumatoid arthritis (RA). The aim of this study is to investigate the relationship between knee deformity and hindfoot alignment and the effect of subtalar joint destruction in patients with RA. METHODS: We retrospectively investigated RA patients (110 patients, 205 limbs) using radiographs in the standing anteroposterior knee, standing lateral foot, and hindfoot alignment views. The grade of destruction at the knee and subtalar joints was assigned using Larsen's grading system. The correlation between the femorotibial and tibiocalcaneal angles and the effect of joint destruction on this correlation were analyzed using Pearson's correlation coefficients. RESULTS: There was moderate correlation between the femorotibial and tibiocalcaneal angles in a group of knees with a Larsen grade of ≥ 4 (r = 0.544, p = 0.0239). This correlation was stronger in a group with less damaged subtalar joints with a Larsen grade of ≤ 3 (r = 0.705, p = 0.0049). CONCLUSION: These findings emphasized the importance of examining foot and ankles in patients with RA who undergo total knee arthroplasty.

An inflammatory myofibroblastic tumor exhibiting immunoreactivity to KIT: a case report focusing on a diagnostic pitfall.

Inflammatory myofibroblastic tumors (IMTs) and gastrointestinal stromal tumors (GISTs) are both spindle cell tumors, and occur rarely in the wall of the urinary bladder. In general, immunostaining allows differentiation of IMTs and GISTs. Most IMTs are positive for anaplastic lymphoma kinase (ALK) and negative for KIT, whereas most GISTs are ALK-negative and KIT-positive. Here, we describe a case of a spindle cell tumor in the wall of the urinary bladder. The spindle cells were positive for both ALK and KIT, and it was thus difficult to determine whether the tumor was an IMT or a GIST. We eventually diagnosed an IMT, because ALK gene rearrangement was confirmed by fluorescent in-situ hybridization. Cytoplasmic staining for KIT and the absence of other GIST markers, including DOG1 and platelet-derived growth factor α, indicated that the tumor was not a GIST. Therefore, IMTs should be included in the differential diagnosis of spindle cell tumors, even those that are KIT-positive.

Simultaneous bilateral posterior interosseous nerve palsy caused by rheumatoid synovitis of the elbows.

A 60-year-old woman with rheumatoid arthritis (RA) developed bilateral posterior interosseous nerve palsy. Her left side recovered after conservative treatment. However, her right side, which had been affected previously, did not recover and required surgery. Although conservative therapy, including administration of biologic agents, should be conducted for tight control of RA activity, we recommend surgical treatment when there is recurrence of the disease.

Ureteral obstruction following transurethral resection of bladder cancer within the Hutch's diverticulum.

Here, we report a rare case of bladder cancer within the left congenital periureteral diverticulum, termed the Hutch's diverticulum. Following transurethral resection of the bladder tumor, repeated pyelonephritis was caused by stricture of the diverticulum orifice and ureter. We attempted transurethral dilation and ureteral stenting, but the obstruction did not improve. The patient's renal dysfunction showed gradual progression due to recurrent left pyelonephritis as well as the ureteral obstruction. Therefore, we finally performed a partial cystectomy, involving stricture and ureteral reimplantation. No tumor recurrence was observed over 39 months, and renal dysfunction did not progress following partial cystectomy.