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A 40-year-old Japanese female was referred to our institution with a high serum lactate dehydrogenase level. Computed tomography (CT) showed a large right adrenal tumor, 14 cm in size without distant metastases. The patient was clinically diagnosed with T2N0M0 adrenocortical carcinoma and underwent right adrenalectomy. The pathological diagnosis was adrenocortical carcinoma with negative surgical margin. The patient was administered mitotane for 2 years as adjuvant therapy. Subsequently, CT revealed asynchronous multiple metastases, including liver, lung, left kidney, and right acetabulum. The patient received 15 courses of EDP (a combination of etoposide, doxorubicin, and cisplatin) plus mitotane therapy, and had stable disease without new lesions.

Aim To identify novel diagnostic markers for renal cell carcinoma (RCC), we analyzed miRNAs in serum extracellular vesicles (EVs). Materials and methods EVs were purified from serum of healthy controls and patients with localized and advanced RCC using T-cell immunoglobulin domain and mucin domain-containing protein 4 conjugated to magnetic beads. miRNA profiling of EVs was conducted by microarray analysis. miRNA expression was examined by quantitative reverse transcription-polymerase chain reaction. Lastly, proteomic analysis of RCC cells transfected with a miRNA inhibitor was performed to identify its potential targets. Results Microarray analysis revealed that nine miRNAs were increased by more than 1.5-fold in EVs from patients with RCC. Among them, miRNA-4525 was significantly elevated; miRNA-4525 expression was higher in RCC tissue than in the adjacent normal tissue. Proteomic analysis identified alpha fetoprotein and albumin as its potential targets. Conclusion These findings suggest the potential of miRNA-4525 in serum EVs as a novel biomarker for advanced RCC.

OBJECTIVE To investigate long-term changes in lower urinary tract symptoms (LUTS) in patients with prostate cancer (PC) who underwent low-dose-rate brachytherapy with iodine-125 (LDR-BT). PATIENTS AND METHODS In this retrospective study, 313 patients with localized PC underwent LDR-BT at Gifu University hospital between August 2004 and December 2013. The International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), and quality of life due to urinary symptoms (IPSS-QOL) were measured before LDR-BT; at 1, 3, 6, 9, 12, 24, 36, 48, and 60 months after LDR-BT; and annually thereafter. Study endpoints were chronological changes in IPSS, OABSS, and IPSS-QOL compared to pretreatment values. A multivariable non-linear regression model with robust sandwich estimator evaluated association between outcomes and time with adjustment for covariates. RESULTS All scores worsened immediately after LDR-BT compared to preoperative scores. However, symptoms improved with time and returned to baseline in 18–36 months. After a 5-year follow-up after LDR-BT, OABSS significantly worsened in almost all patients compared to baseline although there were gradual improvements in less than 5 years after LDR-BT. CONCLUSIONS Our results may be of clinical importance in selecting treatment modalities for patients with localized PC and long-term survival after definitive therapy.

Granulocyte colony-stimulating factor (G-CSF)-producing bladder cancer is a rare variant subtype of bladder cancer with a poor prognosis. Pembrolizumab has improved overall survival in bladder cancer and is widely used as a standard second-line treatment. However, no reports on G-CSF-producing cancer treated by pembrolizumab are available. We report a case of the pathologically evaluated antitumor effect of pembrolizumab, a programmed death-1 immune checkpoint inhibitor antibody, in G-CSF-producing bladder cancer. A 53-year-old male patient underwent 4 courses chemotherapy with a combination of gemcitabine and carboplatin before a radical cystectomy with ileal neobladder. Four months after the surgery, local recurrence was detected in the pelvis and therefore pembrolizumab was used. One week after its administration, the patient showed increased mucus in his urine. A computed tomography scan and cystoscopy revealed a fistula between the ileum and the neobladder. He subsequently underwent partial ileectomy and repair of the neobladder-ileum fistula. Pathology-diagnosed tumor response to pembrolizumab in the metastatic tumor showed predominant infiltration by lymphocytes, unlike that in the primary bladder cancer. The patient has shown complete response and no recurrence at 1 year after the beginning of treatment, and therapy is still continuing. Although many questions still remain regarding the treatment of G-CSF-producing bladder cancer, pathologic evaluation of the present case suggests that treatment with pembrolizumab may be one option for G-CSF-producing bladder cancer that has failed chemotherapy treatment, similar to non-G-CSF-producing bladder cancer.

Background: The aim of this study was to compare the surgical and oncological outcomes and complications of laparoscopic radical cystectomy (LRC) to those of open radical cystectomy (ORC) in patients with muscle-invasive bladder cancer (MIBC). Methods: Our study focused on patients with histologically confirmed stage T2–T4a urothelial carcinoma of the bladder without distant metastases, who underwent LRC (LRC group) or ORC (ORC group). The primary endpoints in this study were the overall survival (OS) and recurrence-free survival (RFS) rates. Results: In this study, 59 patients, 17 underwent LRC and 42 underwent ORC, were enrolled. The 2-year OS rate was 100% in the LRC group and 88.0% in the ORC group (p = 0.85). The 2-year RFS rate was 63.5% in the LRC group and 69.5% in the ORC group (p = 0.321). On multivariate analysis, the histological type, positive lymph node, and positive resection margin were significantly associated with the OS rates. Conclusions: This study suggested that LRC may achieve similar oncological outcomes and fewer perioperative complications and less blood loss compared to ORC. Therefore, LRC should be considered as one of the treatment options for patients with MIBC.

This study aimed to evaluate predictive factors for graft loss in patients who received kidney transplantation (KT) from living kidney donors (LKDs) at a single institute in Japan.Our study focused on patients with end-stage renal disease who underwent KT from LKDs and were followed up for at least 1 year after surgery. The primary end point was graft survival (GS). GS after KT was analyzed using the Kaplan-Meier method. GS according to subgroup classification was analyzed using the log-rank test. A multivariate analysis was performed using a Cox proportional hazard model.The median follow-up period was 105.5 months after KT. The 5- and 10-year GS rates were 97.8% and 96.0% in KT recipients (KTRs) without posttransplant diabetes mellitus (PTDM) and 89.9% and 63.2% in those with PTDM, respectively. The rate of graft loss was significantly higher in KTRs with PTDM than in those without PTDM (P .001). Of the KTRs whose diabetes mellitus (DM) was cured after KT, those who underwent dialysis because of diabetic nephropathy had no graft loss. In the multivariate analysis, the serum creatinine level at 1 month after KT, PTDM, and human leukocyte antigen mismatches were significantly associated with graft loss after KT.In this study, the rate of graft loss in KTRs with PTDM was significantly higher than that of KTRs without PTDM. However, among KTRs whose DM was cured after KT, those who underwent dialysis because of diabetic nephropathy had no graft loss.

A 34-year-old woman underwent total hysterectomy for management of uterine leiomyoma. At the same time, a paraurethral tumor (2 cm in size) was diagnosed based on magnetic resonance imaging (MRI). However, the patient was not treated for the tumor considering its small size. Eight years later, the patient was referred to our institution with a chief complaint of urethral bleeding. Computed tomography revealed a paraurethral mass at the same location, which was 13 cm in size. A percutaneous needle biopsy was performed and the tumor was diagnosed as leiomyoma. Tumor extirpation was performed and immunohistochemical analysis of the specimen demonstrated positive estrogen and progesterone receptors. Recurrence was not observed on MRI taken 6 months after the surgery. Paraurethral leiomyoma is rare, but relatively common in young women.

The risk of malignant neoplasms increases in kidney transplantation (KT) recipients (KTRs). However, Japanese registry studies have not been reported since 2000. We retrospectively reviewed the medical records of 346 patients who underwent KT at Gifu University Hospital, Japan since 2000. Patients were divided into two groups based on whether they developed malignancy after KT or not. The incidence, type of malignancy, risk factors, and prognosis for malignancy were examined. In this study, 22 de novo malignant neoplasms were identified in 20 KTRs (7.3%), with a median follow-up period of 8.2 years. Cumulative incidence of any malignant neoplasms was 1.1% within 1 year and 4.4% within 5 years. The 5-year overall survival (OS) rates were 71.8% in KTRs with malignant neoplasms and 98.6% in KTRs without malignant neoplasms. Uni- and multivariate analysis revealed that age at KT and acute rejection (AR) episode were significant predictors for incidence of malignancy. The development of malignant neoplasms was associated with poor OS and graft survival. We consider that appropriate screening and investigation of symptoms are important for KTRs, particularly for older KTRs at transplantation and those with AR episode.

Background Cabazitaxel (CBZ) is now widely used for prostate cancer (PC) patients resistant to docetaxel (DOC), however, most patients eventually acquire resistance. It will, therefore, be of great benefit to discover novel therapeutic target for the resistance. We aimed to identify candidate therapeutic targets for CBZ-resistance by proteomic analysis of extracellular vesicles (EVs) isolated from serum of DOC-resistant PC patients who later developed CBZ-resistance as well as those harvested from culture medium of DOC- and CBZ-resistant PC cell lines. Methods Using T-cell immunoglobulin domain and mucin domain-containing protein 4 (Tim4) conjugated to magnetic beads, EVs were purified from serum of PC patients with DOC-resistance that was collected before and after acquiring CBZ-resistance and conditioned medium of DOC-resistant (22Rv1DR) and CBZ-resistant (22Rv1CR) PC cell lines. Protein analysis of EVs was performed by nanoLC-MS/MS, followed by a comparative analysis of protein expression and network analysis. The cytotoxic effect of a phosphatidylinositol-3-kinase (PI3K) inhibitor, ZSTK474, was evaluated by WST-1 assay. The expression and phosphorylation of PI3K and PTEN were examined by western blot analysis. Results Among differentially regulated proteins, 77 and 61 proteins were significantly increased in EVs from CBZ-resistant PC cell line and patients, respectively. A comparison between the two datasets revealed that six proteins, fructose-bisphosphate aldolase, cytosolic nonspecific dipeptidase, CD63, CD151, myosin light chain 9, and peroxiredoxin-6 were elevated in EVs from both cell line and patients. Network analysis of the increased EV proteins identified pathways associated with CBZ-resistance including PI3K signaling pathway. ZSTK474 significantly inhibited growth of 22Rv1CR cells and improved their sensitivity to CBZ. In 22Rv1CR cells, PI3K was activated and PTEN that inhibits PI3K was deactivated. Conclusions Proteomic analysis of serum EVs was successfully accomplished by using Tim-4 as a tool to isolate highly purified EVs. Our results suggest that the combination use of CBZ and PI3K inhibitor could be a promising treatment option for CBZ-resistant PC patients.

Aim: To identify novel diagnostic markers for renal cell carcinoma (RCC), we analyzed miRNAs in serum extracellular vesicles (EVs). Materials and Methods: EVs were purified from serum of healthy controls and patients with localized and advanced RCC using T-cell immunoglobulin domain and mucin domain-containing protein 4 conjugated to magnetic beads. miRNA profiling of EVs was conducted by microarray analysis. miRNA expression was examined by quantitative reverse transcription-polymerase chain reaction. Lastly, proteomic analysis of RCC cells transfected with a miRNA inhibitor was performed to identify its potential targets. Results: Microarray analysis revealed that nine miRNAs were increased by more than 1.5-fold in EVs from patients with RCC. Among them, miRNA-4525 was significantly elevated; miRNA-4525 expression was higher in RCC tissue than in the adjacent normal tissue. Proteomic analysis identified alpha fetoprotein and albumin as its potential targets. Conclusion: These findings suggest the potential of miRNA-4525 in serum EVs as a novel biomarker for advanced RCC.

We developed a dual-channel diffuse correlation spectroscopy system, which was validated by simultaneous blood flow measurement of the skeletal muscles of the upper and lower limbs during the head-up-tilt test.

Background Although few studies evaluated the significance of random biopsies under white light cystoscopy (WLC) in patients with non‐muscle‐invasive bladder cancer (NMIBC), the findings are controversial. Aim This aim of this study was to evaluate what kind of preoperative covariates were useful as predictive factors in detecting carcinoma in situ (CIS) from normal‐appearing mucosa using random bladder biopsies under WLC. Methods and Results A total of 229 patients with NMIBC underwent initial TUR followed by random biopsies under WLC at Red Cross Takayama Hospital between 2007 and 2016. These patients underwent TUR with complete resection of intravesical visible tumors followed by random biopsies of normal‐appearing mucosa. In this study, random bladder biopsies of normal‐appearing urothelial mucosa, excluding abnormal mucosa, were carried out with a cold punch in the selected intravesical sites. The covariates included age, gender, the urine cytology result, presence of an abnormal mucosa, number of tumors, size of the largest tumors, configuration of the tumor, and tumor type. Abnormal mucosa was defined as reddish or mossy areas at the time of TUR under WLC. The primary endpoint was to determine what kind of preoperative covariates were useful as predictive factors in detecting CIS from normal‐appearing mucosa using random bladder biopsies under WLC. Finally, 212 patients were evaluated, and 67 patients (31.6%) were diagnosed with CIS from normal‐appearing mucosa. In univariate analysis, positive urine cytology, abnormal mucosa, and the number of tumors were significantly associated with concomitant CIS. On multivariate analysis, positive urine cytology and abnormal mucosa were significantly associated with CIS. Conclusion The patients who were diagnosed with positive urine cytology or abnormal mucosa by WLC are ideal candidates for TUR followed by random biopsy of normal‐appearing mucosa.

INTRODUCTION This study aimed to evaluate the chronologic changes in renal function after laparoscopic partial (LPN) or radical nephrectomy (LRN) in patients with clinical T1 renal cell carcinoma. METHODS In this retrospective study, patients with clinical stage T1 renal cell carcinoma who underwent LPN or LRN were divided into three groups, namely, LPN-A group including LPN patients with WIT ≤25 minutes, LPN-B group including LPN patients with WIT >25 minutes, and LRN group. Perioperative complications that occurred within 30 days after surgery were retrieved. All patients were followed-up every 3 months to evaluate the estimated glomerular filtration rate. The primary endpoint of this study was to assess the chronological changes in renal function after surgery. RESULTS A total of 153 patients were enrolled in this study. The change in estimated glomerular filtration rate between day 1 and 2 weeks after surgery was significantly lower in the LPN-B group than in the LPN-A group (p

A 70-year-old man visited a private hospital with the chief complaint of right lower limb pain. Fluorodeoxyglucose-emission tomography (FDG-PET) showed abnormal uptake in the pubic bone, right femur, and ascending colon. The patient was referred to our hospital for further evaluation. The following tumor marker levels were found : prostate-specific antigen (PSA) 20.57 ng/ml, carcinoembryonic antigen (CEA) 108.5 ng/ml, carbohydrate antigen 19-9 (CA19-9) 1,002.1 U/ml. An open pubic bone biopsy was performed. The pathological diagnosis was metastatic adenocarcinoma from prostate cancer. Prostate and ascending colon cancers were clinically diagnosed as T2bN0M1b and T2N0M0, respectively. Laparoscopic colectomy was performed. Androgen deprivation therapy started immediately and the serum PSA level was maintained at0.2 ng/ml during the follow-up period. However, the CEA and CA19-9 were higher than the normal level 2 years after the surgery. In addition, the FDG-PET revealed abnormal uptake in the pubic bone. Thus, a pubic bone biopsy was performed again. The histological diagnosis was metastatic adenocarcinoma from the ascending colon cancer. Although the patient received combination chemotherapy, he died of colon cancer.

This study aimed to evaluate the association between clinical covariates or the prescribed radiation dose for the prostate and rectal hemorrhage in patients with prostate cancer (PCa) who received iodine-125 low-dose-rate brachytherapy (LDR-BT group) or the combination of LDR-BT and external beam radiation therapy (CMT group). In this retrospective study, we reviewed the clinical records of 298 consecutive PCa patients with clinical stage T1c/T2 who underwent LDR-BT between August 2004 and August 2016 at a single institution. The prescribed minimum peripheral doses were 145 Gy for the LDR-BT group and 104 Gy for the CMT group. The dosimetric parameters analyzed were minimal dose received by 90% of the prostate gland, biologically effective dose, and rectal volume receiving 100% (RV100) or 150% of the prescribed dose. The endpoint of this study was the onset of any-grade clinical rectal hemorrhage after treatment. The median follow-up period was 6.8 years. The 5-year overall survival rate was found to be 98.3%, and two patients (0.7%) reported biochemical recurrence during follow-up period. A total of 33 patients (11%) experienced rectal hemorrhage. However, ≥ grade 2 rectal hemorrhage occurred in eight patients (2.7%). On multivariate analysis, CMT, RV100 ≥ 0.66 mL, and hemorrhoids before treatment were identified as predictors of rectal hemorrhage after radiation therapy. Maximal reduction of the rectal dose seems very important to prevent serious rectal hemorrhage. In addition, we should consider the risk of rectal toxicities in patients with abnormalities in the rectal mucosa, especially hemorrhoids.

Ten years ago, a seventy-year-old female underwent extirpation of a left retroperitoneal tumor that was 58×36 mm in size. The pathological diagnosis was malignant peripheral nerve sheath tumor (MPNST) at that time. The patients visited our hospital with the chief complaint of back pain at ten years after surgery. Computer tomography (CT) showed recurrent tumors at the pancreas and the left kidney. Fine-needle aspiration biopsy was performed because of the possibility of pancreatic tumor. The pathological diagnosis was the recurrence of MPNST. The patient underwent extirpation of the recurrent tumors along with the pancreatic body and tail, transverse colon, spleen and left kidney. The definitive diagnosis was dedifferentiated liposarcoma with murine double minute 2 (MDM2) gene amplification and positive of p16Ink4 (p16). The previously resected tumor also revealed MDM2 gene amplification and positive of p16. Based on these results, our diagnosis in this case was recurrence of dedifferentiated liposarcoma. At 6 months after surgery, the patient had no local recurrence or distant metastases.

We report a fatal case of pembrolizumab-induced myasthenia gravis and myocarditis in a patient with metastatic bladder cancer. A 77-year-old man was aware of eye ptosis and diplopia after three weeks from first infusion of pembrolizumab, an anti-programmed cell death protein 1 monoclonal antibodies. He was diagnosed with myasthenia gravis, because he was positive on the edrophonium test and acetylcholine receptor antibody. As his echocardiography also revealed diffuse loss in wall motion with ejection fraction 29%, he was strongly suspected myocarditis. Although he was treated with prednisone and intravenous immunoglobulin, he was suddenly in cardiac arrest and passed away., Highlights • Appropriate therapy for pembrolizumab-induced MG and myocarditis should rapidly need.

A heat flux sensor was developed with micro-electro-mechanical systems (MEMS) technologies for investigating turbulent heat transfer characteristics in engines. The sensor has three thin-film resistance temperature detectors (RTDs) of a square 315 µm on a side on a 900 µm diameter circle in rotational symmetry. The performances of the MEMS systems sensor were tested in an open combustion chamber and a laboratory engine. In the open chamber tests, it was revealed that the MEMS sensor can measure the wall heat fluxes reflecting flow states of gas phase. In addition, the noise was evaluated as 3.8 kW/m2 with the standard deviation against the wall heat flux of a few hundred kW/m2. From these results, it was proved that the MEMS sensor has the potential to observe turbulent heat transfer on the order over 10 kW/m2 in the engine. In the laboratory engine test, the wall heat flux for continuous 200 cycles was measured with a good signal-to-noise ratio. The noise was evaluated as 13.4 kW/m2 with the standard deviation despite the noisy environment. Furthermore, it was proved that the MEMS sensor has the comparable scale with the turbulence in the engine because the three adjacent detectors measured similar but different phase oscillations in the local instantaneous heat fluxes. In addition, a heat flux vector reflecting the state of the local instantaneous heat transfer was visualized by the adjacent three-point measurement. It is expected that the three-point MEMS sensor will be a useful tool for the engine heat transfer research.

We determined minimum inhibitory concentrations (MICs) of 41 antimicrobial agents for 73 clinical strains of Haemophilus influenzae isolated from the urethra of men with acute urethritis and/or epididymitis and examined the strains for the production of β-lactamase. We also compared their antimicrobial susceptibilities with those of H. influenzae strains from respiratory tract or otorhinolaryngological infections that were reported in Japan. The proportion of β-lactamase-nonproducing ampicillin-resistant strains from acute urethritis and/or epididymitis appeared to be lower, but that of β-lactamase-producing ampicillin-resistant strains appeared to be higher, compared with those from respiratory tract or otorhinolaryngological infections. However, their antimicrobial susceptibilities to a variety of other antimicrobial agents would be similar to those from respiratory tract or otorhinolaryngological infections. Almost all of the strains of H. influenzae from acute urethritis and/or epididymitis were susceptible to the agents, including ceftriaxone, quinolones, macrolides, and tetracyclines, commonly prescribed for treatment of acute urethritis based on the MIC breakpoints recommended by the Clinical and Laboratory Standards Institute. Ceftriaxone and quinolones could be effective on H. influenzae-induced urethritis. However, azithromycin treatment failures were reported in acute urethritis caused by H. influenzae strains considered susceptible to azithromycin. Further studies will be needed to determine MIC breakpoints of antimicrobial agents, which are recommended for treatment of urogenital infections, for H. influenzae strains causing these infections. Nevertheless, this study provides useful data regarding antimicrobial susceptibilities of H. influenzae strains isolated from the urogenital tract, which have rarely been studied.

We can construct passing networks when we regard a player as a node and a pass as a link in football games. Thus, we can analyze the networks by using tools developed in network science. Among various metrics characterizing a network, centrality metrics have often been used to identify key players in a passing network. However, a tolerance to players being marked or passes being blocked in a passing network, namely the robustness of the network, has been poorly understood so far. Because the robustness of a passing network can be connected to the increase of ball possession, it would be deeply related to the outcome of a game. Here, we developed position-dependent passing networks of 45 matches by 18 teams belonging to the Japan Professional Football League. Then, nodes or links were continuously removed from the passing networks by two removal methods so that we could evaluate the robustness of these networks against the removals. The results show that these passing networks commonly contain hubs (key players making passes). Then, we analyzed the most robust networks in detail and found that their full backs increase the robustness by often invoking a heavier emphasis on attack. Moreover, we showed that the robustness of the passing networks and the team performance have a positive correlation., 18 pages, 9 figures

There have been few comprehensive studies on Haemophilus influenza-positive urethritis.In this retrospective study, we enrolled 68 men with H. influenzae-positive urethritis, including coinfections with Neisseria gonorrhoeae, Chlamydia trachomatis, and/or genital mycoplasmas: 2, 3, 20, and 43 treated with ceftriaxone, levofloxacin, sitafloxacin, and extended-release azithromycin (azithromycin-SR), respectively. We assessed microbiological outcomes in 54 men and clinical outcomes in 46 with H. influenzae-positive monomicrobial nongonococcal urethritis. We determined minimum inhibitory concentrations (MICs) of 6 antimicrobial agents for 59 pretreatment isolates.H. influenzae was eradicated from the men treated with ceftriaxone, levofloxacin, or sitafloxacin. The eradication rate with azithromycin-SR was 85.3%. The disappearance or alleviation of urethritis symptoms and the decreases in leukocyte counts in first-voided urine were significantly associated with the eradication of H. influenzae after treatment. For the isolates, ceftriaxone, levofloxacin, sitafloxacin, azithromycin, tetracycline, and doxycycline MICs were ≤0.008-0.25, 0.008-0.5, 0.001-0.008, 0.12-1, 0.25-16, and 0.25-2 μg/mL, respectively. The azithromycin MICs for 3 of 4 strains persisting after azithromycin-SR administration were 1 μg/mL. H. influenzae with an azithromycin MIC of 1 μg/mL increased chronologically.H. influenzae showed good responses to the chemotherapies for urethritis. The significant associations of the clinical outcomes of the chemotherapies with their microbiological outcomes suggested that H. influenzae could play pathogenic roles in urethritis. All isolates, except for one with decreased susceptibility to tetracyclines, were susceptible to the examined agents. However, the increase in H. influenzae with an azithromycin MIC of 1 μg/mL might threaten efficacies of azithromycin regimens on H. influenzae-positive urethritis.

The patient underwent laparoscopic left radical nephrectomy for clear cell renal cell carcinoma (ccRCC). After surgery, the patient had multiple lung metastases and underwent the combination therapy of radiofrequency ablation, interferon-alpha, and inteleukin-2. Thereafter, computed tomography showed multiple lymph node and brain metastases. The patient was administered targeted therapy and radiation. Eventually, the patient suddenly complained of dyspnea. An echocardiogram, coronary angiography and magnetic resonance imaging suggested acute heart failure and pericardial effusion due to a metastatic tumor in the cardiac anteroseptal and posterior wall. Nivolumab was administered for cardiac metastases. The patient has been in stable condition with no progression of cardiac metastases after the administration of nivolumab for 22 months.

Background Apalutamide, a nonsteroidal potent androgen receptor antagonist, was safe and effective in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and metastatic-CRPC (mCRPC) in global studies. In this phase 1 study, safety, pharmacokinetics (PK), and efficacy of apalutamide were evaluated in Japanese patients with mCRPC. Methods In this open-label, multi-center study, patients received apalutamide 240 mg (once-daily, orally) for first 1 week (PK week) during which PK parameters were assessed. 1 week later (Cycle 1 Day1), after reassessing safety, continuous daily dosing (4 weeks/cycle; once-daily orally) was initiated. Endpoints evaluated were: safety, tolerability, PK and antitumour efficacy of apalutamide. Dose-limiting toxicities (DLTs) were evaluated during PK week and Cycle 1. Results All six patients received apalutamide. The most common treatment-emergent adverse events (TEAEs) were abdominal discomfort, nasopharyngitis, dysgeusia, rash, and hot flush [2/6 patients (33.3%) each]. No death or DLTs were reported. Grade 3 TEAEs were spinal-cord compression and renal disorder (1/6 patient each). In continuous daily dosing period, PK steady-state of apalutamide was reached approximately by week 4. A significant accumulation of apalutamide was observed (mean accumulation index 3.55), based on AUC0–24. Median (range) serum prostate-specific antigen level decreased from 54.42 (8.92–310.11) ng/mL at baseline to 11.70 (0.37–47.74) ng/mL at week 12 with ≥ 50% reduction in 4/6 (66.7%) patients and 90% reduction in 2/6 (33.3%) patients. Conclusion Apalutamide had manageable safety profile, without any DLT or any new safety signals, and favourable efficacy in Japanese mCRPC patients. Thus, it was ascertained to be an adequate dosage regimen in Japanese mCRPC patients. Trial registration ClinicalTrials.gov identifier: NCT02162836. Electronic supplementary material The online version of this article (10.1007/s10147-019-01526-7) contains supplementary material, which is available to authorized users.

Unlike urinary tract infection (UTI), asymptomatic bacteriuria (ABU) should not be treated, with some exceptions such as pregnant women and patients who will undergo traumatic urologic interventions. However, there has been no clinically available marker for their differential diagnosis. Exosomes or small extracellular vesicles carry proteins contained in cells from which they are derived, thus having the potential as a biomarker of several diseases. On the basis of the hypothesis that the molecular signature of exosomes in urine may differ between UTI and ABU patients, we examined if urinary exosomes could serve as a marker for their differential diagnosis. Exosomes were isolated by ultracentrifugation or affinity-based method from cell culture medium of monocytic THP-1 and uroepithelial SV-HUC-1 cells and human urine. Protein expression was examined by Western blot analysis, ELISA, and CLEIA. The results showed that the levels of intracellular signalling molecules Akt and ERK and transcription factor NF-κB increased in exosomes isolated from THP-1 and SV-HUC-1 cells cocultured with Escherichia coli and/or treated with lipopolysaccharide. In urinary exosomes of UTI patients, Akt significantly diminished, and an exosomal marker CD9 showed a trend to decrease after treatment with antimicrobial agents. More importantly, Akt and CD9 levels in urinary exosomes were higher in UTI patients than in ABU patients, which was also observed after correction by urine creatinine. Collectively, these results suggest that Akt and CD9 in urinary exosomes could be useful markers for differential diagnosis of UTI and ABU.

OBJECTIVES We treated men with gonococcal urethritis with a single-dose regimen of 1 g of ceftriaxone, which is recommended as the first-line treatment for gonorrhoea in Japan, to determine its microbiological outcomes and tolerability. METHODS We enrolled 255 men with gonococcal urethritis and treated them with a single-dose regimen of 1 g of ceftriaxone. We evaluated its microbiological outcomes and tolerability. We also determined ceftriaxone MICs for pretreatment isolates of Neisseria gonorrhoeae collected from the patients. RESULTS The microbiological efficacy of the ceftriaxone regimen, which was determined between 5 and 9 days after treatment in 111 men based on the Japanese guideline for clinical research on antimicrobial agents in urogenital infections, was 100%. In the 194 men who returned to the clinic between 2 and 41 days after treatment, 191 (98.5%; 95% CI 96.8%-100%) were negative for N. gonorrhoeae after treatment. Ceftriaxone MICs determined for 136 pretreatment isolates obtained from these 194 men ranged from 0.001 to 0.25 mg/L. One isolate persisting after treatment exhibited a ceftriaxone MIC of 0.008 mg/L. For two isolates persisting after treatment, ceftriaxone MICs were not determined. Seven adverse events were observed in 7 (3.2%) of the 220 men treated with the ceftriaxone regimen. Four men had diarrhoea classified as grade 1. Three had urticaria during ceftriaxone administration, with one event classified as grade 1 and two events classified as grade 3. CONCLUSIONS A single-dose regimen of 1 g of ceftriaxone was microbiologically effective against gonococcal urethritis and was safe and tolerable.

Objectives To detect microorganisms responsible for male acute urethritis and to define the microbiology of non-gonococcal urethritis. Methods The present study comprised 424 men with symptoms and signs compatible with acute urethritis. Their urethral swabs and first-voided urine underwent detection of the microorganisms. Demographic characteristics and clinical features of Mycoplasma genitalium-, Ureaplasma urealyticum-, Haemophilus influenza-, adenovirus- or Herpes simplex virus-positive monomicrobial non-gonococcal urethritis, or all-examined microorganism-negative urethritis in heterosexual men were compared with urethritis positive only for Chlamydia trachomatis. Results Neisseria gonorrhoeae was detected in 127 men (30.0%). In 297 men with non-gonococcal urethritis, C. trachomatis was detected in 143 (48.1%). In 154 men with non-chlamydial non-gonococcal urethritis, M. genitalium (22.7%), M. hominis (5.8%), Ureaplasma parvum (9.1%), U. urealyticum (19.5%), H. influenzae (14.3%), Neisseria meningitidis (3.9%), Trichomonas vaginalis (1.3%), human adenovirus (16.2%), and Herpes simplex virus types 1 (7.1%) and 2 (2.6%) were detected. Although some features of monomicrobial non-chlamydial non-gonococcal urethritis or all-examined microorganism-negative urethritis were significantly different from those of monomicrobial chlamydial non-gonococcal urethritis, most features were superimposed. Conclusions Predicting causative microorganisms in men with non-gonococcal urethritis based on demographic and clinical features is difficult. However, the present study provides useful information to better understand the microbiological diversity in non-gonococcal urethritis, and to manage patients with non-gonococcal urethritis appropriately.

We retrieved clinical data of 13 men having herpes simplex virus (HSV)-induced non-gonococcal urethritis (NGU) without visible herpetic lesions. They visited a clinic in Sendai, Japan, between April 2013 and December 2015. All the men complained of dysuria. Meatitis was observed in 9 of the 13 men. Mononuclear cells were observed in the urethral smears from 9 men. The 13 men were treated with azithromycin or sitafloxacin regimen. First-voided urine (FVU) specimens became negative for HSV in 8 of the 10 men who returned to the clinic after antibacterial treatment, and urethritis symptoms were alleviated. However, herpetic lesions were observed at the follow-up visits in 3 men, and 2 of them were still positive for HSV in their FVU. HSV could be a cause of acute urethritis without causing visible herpetic lesions. The shedding of HSV from the urethra would spontaneously cease with alleviation of urethritis symptoms in most cases of HSV-induced NGU without antiviral therapy. However, new herpetic lesions could be developed in some cases. Early antiviral therapy is beneficial for patients with HSV infections. The development of meatitis and the mononuclear cell response in the urethral smear could be helpful to diagnose HSV-induced NGU. Therefore, we should presumptively initiate anti-HSV therapy for patients with signs and symptoms suggestive of HSV-induced NGU at their first presentation.

Radical cystectomy remains the gold standard for treatment of muscle-invasive bladder cancer. Robot-assisted radical cystectomy has technical advantages over laparoscopic radical cystectomy and has emerged as an alternative to open radical cystectomy. Despite the advancements in robotic surgery, experience with total intracorporeal reconstruction of urinary diversion remains limited. Most surgeons have carried out the hybrid approach of robot-assisted radical cystectomy and extracorporeal reconstruction of urinary diversion, as intracorporeal reconstruction of urinary diversion remains technically challenging. However, intracorporeal reconstruction of urinary diversion might potentially proffer additional benefits, such as decreased fluid loss, reduction in estimated blood loss and a quicker return of bowel function. The adoption of intracorporeal ileal neobladder reconstruction has hitherto been limited to high-volume academic institutions. In the present review, we compare the totally intracorporeal robot-assisted radical cystectomy approach with open radical cystectomy and robot-assisted radical cystectomy + extracorporeal reconstruction of urinary diversion in muscle-invasive bladder cancer patients.

We analyzed the 23S rRNA, gyrA and parC genes of Chlamydia trachomatis DNAs from men with urethritis and determined microbiological outcomes of an extended-release azithromycin (azithromycin-SR) regimen (2 g once daily for 1 day) and a sitafloxacin regimen (100 mg twice daily for 7 days) for chlamydial urethritis to clarify the macrolide and fluoroquinolone resistance status of clinical strains of C. trachomatis. We amplified the portions of 2 alleles of the 23S rRNA gene and the gyrA and parC genes from C. trachomatis DNAs in 284 first-voided urine specimens from men with chlamydial urethritis by PCR and sequenced their PCR products. We enrolled 369 men with chlamydial urethritis, comprising 314 and 55 treated with the azithromycin-SR regimen and the sitafloxacin regimen, respectively. Alleles 1 and/or 2 of the 23S rRNA gene were analyzed in 162 specimens. No mutations were found in the sequenced regions, including the central portion of domain V. The gyrA and parC genes were analyzed in 118 and 113 specimens, respectively. No amino acid changes were found within the quinolone resistance-determining region of the gyrA gene and in the sequenced region of the parC gene. The microbiological outcomes of the azithromycin-SR and sitafloxacin regimens were assessed in 176 and 30 men, respectively. The eradication rates were 96.0% (95% CI 93.1%–98.9%) for the azithromycin-SR regimen and 100% for the sitafloxacin regimen. Clinical strains of C. trachomatis with macrolide and/or fluoroquinolone resistance would be uncommon, and azithromycin or fluoroquinolone regimens could be recommended as treatments for chlamydial infections.

Ureaplasma parvum, which has been recognised as a coloniser in the male urethra, is detected in some men with non-gonococcal urethritis. In this study, we quantified the 16 S rRNA genes of U. parvum by a real-time polymerase chain reaction-based assay in first-voided urine from 15 symptomatic and 38 asymptomatic men who were positive only for U. parvum. We also determined the leukocyte counts by automated quantitative urine particle analysis in their first-voided urine. Positive correlations were observed between copies of the 16 S rRNA genes of U. parvum/ml and the leukocyte counts/µl in first-voided urine ( p = 0.0019). The loads of ≥104 copies of the 16 S rRNA gene/ml, corresponding to ≥5 × 103 cells of U. parvum/ml, were significantly associated with the presence of ≥12.5 leukocytes/µl in first-voided urine that might document the presence of inflammatory responses in the urethra. However, a large portion of the subjects (83.0%) had bacterial loads of 3 cells of U. parvum/ml, and 79.5% of them showed

To the Editor: In 2009, 2010, and 2013, Neisseria gonorrhoeae strains H041 (ceftriaxone MIC of 2 mg/L), F89 (ceftriaxone MIC of 1 mg/L), and A8806 (ceftriaxone MIC of 0.5 mg/L) were isolated from samples from patients in Japan (1), France (2) and Australia (3), respectively. In Japan, no other clinical N. gonorrhoeae strains with decreased susceptibility to ceftriaxone were reported until 2014, when clinical strain {"type":"entrez-nucleotide","attrs":{"text":"GU140106","term_id":"268370439","term_text":"GU140106"}}GU140106 (ceftriaxone MIC of 0.5 mg/L) was isolated from a man in in Nagoya, Japan. We report details of this case and sequencing results of the penA gene for the strain. The study was approved by the Institutional Review Board of the Graduate School of Medicine, Gifu University, Japan. N. gonorrhoeae strain {"type":"entrez-nucleotide","attrs":{"text":"GU140106","term_id":"268370439","term_text":"GU140106"}}GU140106 was isolated from a urethral swab sample from a man with acute urethritis. The man had received fellatio, without condom use, from a female sex worker in Nagoya in December 2013. He visited our clinic in January 2014 for urethral discharge. Culture of a urethral swab sample was positive for N. gonorrhoeae. We used the Cobas 4800 CT/NG Test (Roche Molecular Systems Inc., Pleasanton, CA, USA) to test a first-voided urine sample; results were positive for N. gonorrhoeae but negative for Chlamydia trachomatis. The infection was treated with a single-dose regimen of ceftriaxone (1 g) administered by intravenous drip infusion. Two weeks later, the man reported no symptoms, and his first-voided urine sample was negative for leukocytes. The test-of-cure for N. gonorrhoeae was not performed. The female sex worker could not be examined for the presence of N. gonorrhoeae strain {"type":"entrez-nucleotide","attrs":{"text":"GU140106","term_id":"268370439","term_text":"GU140106"}}GU140106 in her pharynx. The strain was confirmed to be a gonococcal species by testing with Gonochek-II (TCS Biosciences Ltd, Buckingham, UK), the HN-20 Rapid system identification test (Nissui, Tokyo, Japan), and the Aptima Combo 2 assay for CT/NG (Hologic, Inc., Bedford, MA, USA) and by 16S rRNA gene sequencing and porA pseudogene PCR (4). MICs of antimicrobial drugs for {"type":"entrez-nucleotide","attrs":{"text":"GU140106","term_id":"268370439","term_text":"GU140106"}}GU140106 were as follows, as determined by using the agar dilution method: 2.0 mg/L for penicillin G, 1.0 mg/L for tetracycline, 2.0 mg/L for cefixime, 0.5 mg/L for ceftriaxone, 8.0 mg/L for levofloxacin, 0.5 mg/L for azithromycin, and 32.0 mg/L spectinomycin. The strain was determined to be resistant to penicillin G, tetracycline, cefixime, ceftriaxone, and levofloxacin, according to criteria of the European Committee on Antimicrobial Susceptibility Testing (5) The penA gene of strain {"type":"entrez-nucleotide","attrs":{"text":"GU140106","term_id":"268370439","term_text":"GU140106"}}GU140106 was sequenced as previously described (6); results showed the presence of a novel mosaic penicillin-binding protein 2 (PBP2; GenBank accession no. {"type":"entrez-nucleotide","attrs":{"text":"LC056026","term_id":"965690016","term_text":"LC056026"}}LC056026) (Figure). Multilocus sequence typing (MLST) and N. gonorrhoeae multiantigen sequence typing (NG-MAST) of {"type":"entrez-nucleotide","attrs":{"text":"GU140106","term_id":"268370439","term_text":"GU140106"}}GU140106 were performed as previously reported (8,9). MLST assigned strain {"type":"entrez-nucleotide","attrs":{"text":"GU140106","term_id":"268370439","term_text":"GU140106"}}GU140106 to sequence type 7363, the same as strains H041 and A8806 (1,2). NG-MAST assigned strain {"type":"entrez-nucleotide","attrs":{"text":"GU140106","term_id":"268370439","term_text":"GU140106"}}GU140106 to sequence type 6543. MLST and NG-MAST results for {"type":"entrez-nucleotide","attrs":{"text":"GU140106","term_id":"268370439","term_text":"GU140106"}}GU140106 differed from those for F89 (3). Figure Sequences of altered amino acids in penicillin-binding protein 2 (PBP2) of Neisseria gonorrhoeae strains with decreased susceptibility to oral cephalosporins and strains with resistance to ceftriaxone. Strain {"type":"entrez-nucleotide","attrs":{"text":"GU140106","term_id":"268370439","term_text":"GU140106"}} ... Since the naming of the mosaic PBP2 associated with decreased susceptibilities to oral cephalosporins as pattern X (6), various PBP2 mosaic structures have been discovered. Mosaic PBP2 structures are basically composed of fragments analogous to PBP2s in Neisseria species. Before strain H041 emerged, strains harboring mosaic PBP2s had been resistant to oral cephalosporins but susceptible to ceftriaxone. H041 (ceftriaxone MIC of 2 mg/L) had additional novel amino acid changes, including A311V, V316P, and T483S, in its mosaic PBP2. The presence of substitutions A311V, V316P, and T483S was reported to be responsible for resistance to ceftriaxone (7). Like strain H041, strains {"type":"entrez-nucleotide","attrs":{"text":"GU140106","term_id":"268370439","term_text":"GU140106"}}GU140106 and A8806 (ceftriaxone MICs of 0.5 mg/L) had substitutions A311V and T483S, but instead of substitution V316P, they had substitution V316T. In addition, {"type":"entrez-nucleotide","attrs":{"text":"GU140106","term_id":"268370439","term_text":"GU140106"}}GU140106 had several changes in positions 227–281 that were not present in other strains. These alterations might also contribute to the decreased susceptibility to ceftriaxone. On the basis of pharmacodynamic analyses (10), a 1-g dose of ceftriaxone (the recommended first-line treatment for gonorrhea in Japan) would be effective against genital gonorrhea caused by strains exhibiting decreased susceptibility to ceftriaxone (e.g., strains {"type":"entrez-nucleotide","attrs":{"text":"GU140106","term_id":"268370439","term_text":"GU140106"}}GU140106 and A8806). However, such strains could be resistant to lower-dose regimens, including 250-mg and 500-mg doses of ceftriaxone. This N. gonorrhoeae strain, {"type":"entrez-nucleotide","attrs":{"text":"GU140106","term_id":"268370439","term_text":"GU140106"}}GU140106, was isolated from the urethra of a man who received fellatio from a female sex worker; thus, the bacteria could have derived from her pharynx. N. gonorrhoeae strain H041 was previously isolated from the pharynx of a female sex worker (1). To prevent the emergence and spread of ceftriaxone-resistant N. gonorrhoeae, pharyngeal gonorrhea must be treated. It is uncertain whether a 1-g dose of ceftriaxone would be effective against pharyngeal gonorrhea caused by strains with decreased susceptibility to ceftriaxone, and this regimen might facilitate the selection of such strains from oral cephalosporin-resistant strains in the pharynx. The emergence of N. gonorrhoeae {"type":"entrez-nucleotide","attrs":{"text":"GU140106","term_id":"268370439","term_text":"GU140106"}}GU140106 in Japan suggests that new strategies (not just increased ceftriaxone doses), including combination treatment with ceftriaxone and another class of antimicrobial drugs and multiple dose regimens of ceftriaxone, might be required to treat pharyngeal gonorrhea.

Background BK virus (BKV) is the cause of nephropathy. Because BKV nephropathy can progress to graft loss, early diagnosis of BKV infection is very important. In this study, we aimed to investigate the utility of quantifying cells with intranuclear inclusion bodies (decoy cells) in urinary sediment for the screening and monitoring of BKV infection in renal transplant recipients at our hospital. Methods This was a retrospective single-center study. Urine sediment examination was performed at each outpatient visit, and the number of decoy cells was measured in the whole microscopic field. Patients (n = 41) were divided into the BK viremia group (blood positive for BKV DNA by polymerase chain reaction [PCR]) and non-BK viremia group (blood negative for BKV DNA by PCR), and the decoy cell count in urinary sediments was examined. Results The maximum decoy cell count was significantly higher (P = 0.04) in the BK viremia group than in the non-BK viremia group. In the receiver operating characteristic curve for the maximum decoy cells, the cutoff value was 507 cells. The area under the receiver operating characteristic curve was 0.8774 (95% confidence interval, 0.7739-0.9810). The number of decoy cells at the time of appearance in the BK viremia group was not significantly different from that in the non-BK viremia group. However, the BK viremia group showed an increasing trend, whereas the non-BK viremia group showed a decreasing trend, in the number of decoy cells. There was a positive correlation between the number of decoy cells and the data from the urine BKV-DNA PCR quantification (correlation coefficient [r] = 0.74). Conclusions Measurement of decoy cells in urinary sediments may predict early BKV infection, and if performed quickly, it may be useful for screening and continuous monitoring of BKV infection in renal transplant recipients.

Of 73 clinical strains of Haemophilus influenzae isolated from the urethra of men with urogenital infections, we enrolled 6 strains (8.2%) with levofloxacin (LVFX) minimum inhibitory concentrations (MICs) of ≥0.03 μg/ml in this study. All the strains were isolated from non-gonococcal urethritis (NGU). We amplified the quinolone resistance-determining region of the gyrA gene and the analogous region of the parC gene from bacterial DNAs by PCR and sequenced the PCR products. Two strains with a LVFX MIC of 0.03 μg/ml had an amino acid change of Asp88 to Gly in GyrA. One with a LVFX MIC of 0.06 μg/ml had a change of Asp88 to Tyr in GyrA. Two with respective LVFX MICs of 0.12 and 0.25 μg/ml had a change of Ser84 to Leu in GyrA. One with a LVFX MIC of 1 μg/ml had changes of Ser84 to Leu in GyrA and of Ser84 to Ile in ParC. Multilocus sequence typing showed two strains with a change of Asp88 to Gly in GyrA had the same sequence type, but the others had sequence types different from each other. Single amino acid changes in GyrA alone or single changes in both GyrA and ParC could contribute to decreased susceptibility to fluoroquinolones in H. influenzae isolates from NGU. Most of the isolates with GyrA and/or ParC alterations would be multiclonal. The prevalence of such isolates would be relatively low, and they would still be susceptible to fluoroquinolones commonly prescribed for treatment of NGU.

The authors present a case report of collecting duct carcinoma (CDC) that responded to nivolumab, a programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody, following the failure of systemic treatment with chemotherapy and targeted therapy. The patient underwent right radical nephrectomy and segmentectomy of the lung following chemotherapy. Fifteen months following the first surgery, segmentectomy and subsequent second-line chemotherapy were performed for recurrence in the lung. Targeted therapy with temsirolimus for recurrence of the lung and lymph node metastases was ultimately used for 30 months. However, the temsirolimus treatment failed to suppress the growth of metastatic lesions. Nivolumab resulted in complete response of the lung metastasis, and it stabilized the lymph node metastasis. PD-L1 was highly expressed in both primary tumor and the metastatic regions. Therapy with nivolumab is ongoing. These findings suggest that treatment with nivolumab may be considered for metastatic and treatment-failure CDC.

We propose an innovative method for aluminum doping of 4H-SiC with passivation films, induced by XeF excimer laser irradiation in AlCl3 aqueous solution (28.6 wt%). A 100-nm thick Si passivation film was deposited on an n-type 4H-SiC substrate by physical vapor deposition. Using a laser beam (200 μm × 170 μm) with an irradiation fluence of 0.5–5.0 J/cm 2 , 1–300 shots were administered. After laser irradiation of 1.0 J/cm 2 and 300 shots, an Al-Si-O compound film was formed on the SiC surface. The compound film was removed by chemical wet etching and plasma treatment. After the removal of the compound film, no irradiation damage was observed on the SiC surface. From the results of secondary ion mass spectrometry measurements, high concentration aluminum doping (about 1 × 10 20 /cm 3 at the surface) was confirmed. The I-V characteristics of the junction between the n-type substrate and the irradiation area indicated clear rectification with a large on/off ratio of 9 decades in the range of ±10 V. When forward biased, electroluminescence phenomenon with a peak at 387 nm, corresponding to the electroluminescence of SiC’s band gap, was confirmed. These results prove the achievement of Al doping of n-type SiC to p-type using laser irradiation without any damage to the SiC surface.

We observed fluoroquinolone treatment failures in 2 men with Mycoplasma genitalium-positive non-gonococcal urethritis in Japan. A fluoroquinolone regimen of sitafloxacin 100 mg twice daily for 7 days failed to eradicate M. genitalium. In both cases, M. genitalium had fluoroquinolone resistance-associated amino acid changes both in GyrA and ParC and a macrolide resistance-associated mutation in the 23S rRNA gene. The emergence of such multi-drug resistant strains can threaten antimicrobial chemotherapy for M. genitalium infections in Japan, because we will lose the first- (azithromycin) and second-line (sitafloxacin) antimicrobial agents to treat M. genitalium infections. We prescribed an extended minocycline regimen of minocycline 100 mg twice daily for 14 days for our patients, and the regimen was successful in eradicating the M. genitalium. The extended minocycline regimen might be an option that we can try when treating multi-drug resistant M. genitalium infections in clinical practice.

A 26-year-old woman with gross hematuria was seen in a previous hospital. Magnetic resonance imaging (MRI) showed a tumor at the dome of the urinary bladder with invasion outside of the bladder wall. The patient underwent transurethral resection of the bladder tumor (TUR-BT). From the result of the pathological examination, the tumor was suggested to be carcinosarcoma of the bladder. The patient was then referred to our hospital for treatment. We performed radical cystectomy and ileal conduit diversion. Pathological examination of the excised specimen revealed an inflammatory myofibroblastic tumor as the basis for immunostaining of anaplastic lymphoma kinase (ALK).