Decreased GM3 correlates with proteinuria in minimal change nephrotic syndrome and focal segmental glomerulosclerosis.

BACKGROUND: Glycolipids on cell membrane rafts play various roles by interacting with glycoproteins. Recently, it was reported that the glycolipid GM3 is expressed in podocytes and may play a role in podocyte protection. In this report, we describe the correlation between changes in GM3 expression in glomeruli and proteinuria in minimal change nephrotic syndrome (MCNS) and focal segmental glomerulosclerosis (FSGS) patients. METHODS: We performed a case-control study of the correlation between nephrin/GM3 expression levels and proteinuria in MCNS and FSGS patients who underwent renal biopsy at our institution between 2009 and 2014. Normal renal tissue sites were used from patients who had undergone nephrectomy at our institution and gave informed consent. RESULTS: Both MCNS and FSGS had decreased GM3 and Nephrin expression compared with the normal (normal vs. MCNS, FSGS; all p < 0.01). Furthermore, in both MCNS and FSGS, GM3 expression was negatively correlated with proteinuria (MCNS: r = - 0.61, p < 0.01, FSGS: r = - 0.56, p < 0.05). However, nephrin expression had a trend to correlate with proteinuria in FSGS (MCNS: r = 0.19, p = 0.58, FSGS: r = - 0.48, p = 0.06). Furthermore, in a simple linear regression analysis, GM3 expression also correlated with proteinuric change after 12 months of treatment (MCNS: r = 0.40, p = 0.38, FSGS: r = 0. 68, p < 0.05). CONCLUSION: We showed for the first time that decreased GM3 expression correlates with proteinuria in MCNS and FSGS patients. Further studies are needed on the podocyte-protective effects of GM3.

Renal functional outcome after laparoscopic partial nephrectomy using dynamic renal scintigraphy.

INTRODUCTION To explore postoperative operation-side renal functional outcome after laparoscopic partial nephrectomy (LPN) using dynamic renal scintigraphy. MATERIALS AND METHODS: Between July 2006 and December 2014, 62 patients with localized renal tumor received ischemic LPN at our institution. Preoperative, 6 months postoperative, and 12 months postoperative split renal functions were evaluated by dynamic renal scintigraphy using radionuclide technetium-99m-mercaptoacetyltriglycine. Postoperative operation-side renal function was calculated. To assess the significant factors affecting postoperative operation-side renal functional decrease, simple regression and multiple regression analyses were carried out. RESULTS: Postoperative operation-side renal functions were significantly decreased to 86.6% at 6 months and 86.9% at 12 months postoperatively (p < 0.0001). Simple regression analyses revealed that postoperative operation-side renal functions were significantly decreased with prolonged warm ischemia time at 6 months and 12 months postoperatively (p = 0.0058 and 0.0032, respectively). Multiple regression analysis identified warm ischemia time as an independent predictive factor for operation-side renal functional decreases at 6 months and 12 months postoperatively (p = 0.0158 and 0.0109, respectively). CONCLUSIONS: Irreversible renal damage using dynamic renal scintigraphy after LPN was observed. With prolongation of warm ischemia time during LPN, postoperative operation-side renal function was significantly decreased.

[A Case of Retroperitoneal Mature Teratoma Successfully Treated by Laparoscopic Adrenalectomy].

We report a case of retroperitoneal mature teratoma which was successfully treated by laparoscopic adrenalectomy. A 37-year-old woman complaining of right abdominal discomfort was referred to our hospital because computed tomography showed an adrenal tumor at another hospital. Magnetic resonance imaging showed a 10 cm adrenal tumor that consisted of fat with calcification. Endocrine examination showed no abnormal findings. Under the suspicion of myelolipoma, we performed laparoscopic right adrenalectomy. Histological diagnosis was mature teratoma. The patient had no recurrence at 5 years after surgery.

Antifibrotic effects of cyclosporine A on TGF-ß1-treated lung fibroblasts and lungs from bleomycin-treated mice: role of hypoxia-inducible factor-1α.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disorder that is characterized by aberrant tissue remodeling and the formation of fibroblastic foci that are composed of fibrogenic myofibroblasts. TGF-ß1 is one of the factors that are responsible for fibrosis as it promotes fibroblast to myofibroblast differentiation (FMD) and is associated with up-regulation of α-smooth muscle actin. Therefore, inhibition of FMD may represent an effective strategy for the treatment of IPF. Here, we describe the treatment of human lung fibroblasts (WI-38 and HFL-1 cells) with cyclosporine A (CsA), which reduces TGF-ß1-induced FMD via degradation of hypoxia-inducible factor-1α (HIF-1α). In addition, in primary myofibroblast-like cells that were obtained from a patient with pulmonary fibrosis, treatment with CsA and an HIF-1α inhibitor (HIFi) decreased the expression levels of α-smooth muscle actin and fibronectin, which indicated that CsA and HIFi promote dedifferentiation of myofibroblasts. In mice intratracheally administered CsA or HIFi at an early fibrotic stage [7, 8, and 9 d postinstillation (dpi) of bleomycin], marked alleviation of lung fibrosis was observed at 14 dpi. These results suggest that CsA exhibits antifibrotic effects by degrading HIF-1α and that the CsA-HIF-1α axis provides new insights into therapeutic options for the treatment of IPF.-Yamazaki, R., Kasuya, Y., Fujita, T., Umezawa, H., Yanagihara, M., Nakamura, H., Yoshino, I., Tatsumi, K., Murayama, T. Antifibrotic effects of cyclosporine A on TGF-ß1-treated lung fibroblasts and lungs from bleomycin-treated mice: role of hypoxia-inducible factor-1α.

[Recurrent Urothelial Carcinoma in the Uretero-Vesical Junction Treated with Partial Ureterectomy and Ureteroneocystostomy during Long-Term Follow-Up : A Case Report].

A 54-year-old woman who had been treated with transurethral resection of bladder tumor for nonmuscle invasive urothelial carcinoma approximately nine years before presented with gross hematuria. Cystoscopy demonstrated a papillary tumor at the left side of the ureteral orifice. Magnetic resonance imaging showed a 1.3 cm non-muscle invasive lesion in the lower ureter from the ureteral orifice. She suffered from connective tissue disease treated with steroids. To avoid renal failure, we performed partial ureterectomy and ureteroneocystostomy. Pathological findings revealed pT1 urothelial carcinoma with negative surgical margin. There have been no signs of recurrence during eight years of follow-up after the last treatment.

Impact of five-tiered Gleason grade groups on prognostic prediction in clinical stage T3 prostate cancer undergoing high-dose-rate brachytherapy.

BACKGROUND: We evaluated a five-tiered Gleason grade groups arising from the 2014 International Society of Urological Pathology consensus conference on prognostic prediction in clinical stage T3a (extracapsular invasion) and T3b (seminal vesicle involvement) prostate cancer undergoing high-dose-rate brachytherapy (HDR-BT). METHODS: From November 2003 to December 2012, 283 patients with stage T3 prostate cancer received HDR-BT and external beam radiation therapy (EBRT) with long-term androgen deprivation therapy (ADT). Of these, 203 (72%) and 80 (28%) patients had stage T3a and T3b disease, respectively. The mean dose to 90% of the planning target volume was 7.5 Gy/fraction of HDR-BT. After five fractions, EBRT with 10 fractions of 3 Gy was administered. All patients first underwent ≥6 months of neoadjuvant ADT, and adjuvant ADT continued for 36 months. Median follow-up was 74 months from the start of radiotherapy. RESULTS: The 10-year biochemical recurrence (BCR) -free rate for stage T3a and T3b disease was 79% and 64%, respectively (P = 0.0083). The 10-year cancer-specific survival (CSS) rate for stage T3a and T3b was 96% and 91%, respectively (P = 0.0305). Although grade groups ≥4 were independent predictors for BCR in cT3a patients (P = 0.0270), they failed to significantly predict prostate cancer-specific mortality (PCSM) among cT3a patients. Among cT3b patients, grade group 5 was a significant predictor of both BCR (P = 0.0017) and PCSM (P = 0.0233). Among stage T3a patients, no significant difference existed in 10-year CSS between grade groups 5 and 4 (94% vs 97%, P = 0.3960). In contrast, grade group 5 had a significantly worse outcome in 10-year CSS than grade group 4 among stage T3b patients (74% vs 100%, P = 0.0350). CONCLUSIONS: Stage T3a patients with grade groups 4/5 and stage T3b with grade group 4 had fairly low PCSM risk. Approximately one of four patients among stage T3b patients with grade group 5 showed PCSM after combined HDR-BT and EBRT with long-term ADT. Stage T3b patients with grade group 5 may have a greater risk for PCSM.

Overall prognostic impact of C-reactive protein level in patients with metastatic renal cell carcinoma treated with sorafenib.

C-reactive protein (CRP) is an independent prognostic factor for renal cell carcinoma (RCC). The aim of the present study was to investigate the overall prognostic impact of CRP in patients with metastatic RCC treated with sorafenib. Between April 2008 and December 2014, 40 consecutive patients with metastatic RCC were treated with sorafenib at our institution. The patients were divided into two cohorts according to the pretreatment CRP level: (i) a normal CRP cohort (≤0.30 mg/dl) and (ii) an elevated CRP cohort (>0.30 mg/dl). Kaplan-Meier overall survival analysis was carried out. The effects of selected variables on survival were assessed by multivariate regression using the Cox proportional hazards model. The normal CRP cohort included 16 patients (40.0%) and the elevated CRP cohort included 24 patients (60.0%). The normal CRP cohort showed significantly longer overall survival than the elevated CRP cohort (median, 52.0 vs. 17.0 months; P=0.0072). On multivariate analysis, normal CRP predicted longer overall survival (hazard ratio, 0.367; 95% confidence interval, 0.147-0.914; P=0.0313). Pretreatment normal CRP predicted better overall survival in patients with metastatic RCC treated with sorafenib and CRP level may be a useful biomarker for predicting overall survival of patients treated with sorafenib.

Clinical characteristics of pulmonary nocardiosis in immunocompetent patients.

Pulmonary nocardiosis is a rare but potentially serious infection typically in immunosuppressed patients (ISPs). It is also known to occur in immunocompetent patients (ICPs). However, little is currently known regarding the clinical characteristics and radiographic findings of pulmonary nocardiosis specifically in ICPs. In this study, 30 patients with pulmonary nocardiosis were identified and 10 were considered to be colonized. Of all patients with pulmonary nocardiosis, 12 patients were ICPs and 18 were ISPs. Although half of ISPs were infected by Nocardia nova, ICPs were affected by various Nocardia species. Compared with ISPs, chest CT findings of ICPs showed a higher prevalence of bronchiectasis (67% vs 6%, p < .01) and centrilobular nodular opacities (67% vs 11%, p < .01), both of which are often seen in pulmonary nontuberculous mycobacterial disease. Additionally, nontuberculous mycobacterium was isolated from 6 of 21 ICPs with positive Nocardia species culture. Therefore, we recommend that physicians carefully differentiate pulmonary nocardiosis from pulmonary nontuberculous mycobacterial disease in ICPs.

[A Case of Primary Adrenal Malignant Lymphoma with Inferior Vena Cava Thrombus].

We report a case of primary adrenal malignant lymphoma with inferior vena cava thrombus which was successfully treated by surgical resection and chemotherapy. A 77-year-old woman complained of right back pain. Computed tomography and magnetic resonance imaging showed right adrenal tumor which had a diameter of 27 mm with inferior vena cava thrombus. Under the diagnosis of malignant adrenal tumor, surgical resection and vena cava replacement were performed. Histopathological examination revealed diffuse large B-cell lymphoma. After the operation, she received 6 courses of adjuvant chemotherapy, and has been alive without evidence of recurrence for 3 years.

Bidirectional role of IL-6 signal in pathogenesis of lung fibrosis.

BACKGROUND: Various signals are known to participate in the pathogenesis of lung fibrosis. Our aim was to determine which signal is predominantly mobilized in the early inflammatory phase and thereafter modulates the development of lung fibrosis. METHODS: Mice received a single dose of 3 mg/kg body weight of bleomycin (BLM) and were sacrificed at designated days post-instillation (dpi). Lung homogenates and sections from mice in the early inflammatory phase were subjected to phospho-protein array analysis and immunofluorescence studies, respectively. Bronchoalveolar lavage fluid (BALF) from mice was subjected to an enzyme-linked immunosorbent assay (EIA) for interleukin (IL)-6 and evaluation of infiltrated cell populations. The effects of endogenous and exogenous IL-6 on the BLM-induced apoptotic signal in A549 cells and type 2 pneumocytes were elucidated. In addition, the effect of IL-6-neutralizing antibody on BLM-induced lung injury was evaluated. RESULTS: Phospho-protein array revealed that BLM induced phosphorylation of molecules downstream of the IL-6 receptor such as Stat3 and Akt in the lung at 3 dpi. At 3 dpi, immunofluorescence studies showed that signals of phospho-Stat3 and -Akt were localized in type 2 pneumocytes, and that BLM-induced IL-6-like immunoreactivity was predominantly observed in type 2 pneumocytes. Activation of caspases in BLM-treated A549 cells and type 2 pneumocytes was augmented by application of IL-6-neutralizing antibody, a PI3K inhibitor or a Stat3 inhibitor. EIA revealed that BLM-induced IL-6 in BALF was biphasic, with the first increase from 0.5 to 3 dpi followed by the second increase from 8 to 10 dpi. Blockade of the first increase of IL-6 by IL-6-neutralizing antibody enhanced apoptosis of type 2 pneumocytes and neutrophilic infiltration and markedly accelerated fibrosis in the lung. In contrast, blockade of the second increase of IL-6 by IL-6-neutralizing antibody ameliorated lung fibrosis. CONCLUSIONS: The present study demonstrated that IL-6 could play a bidirectional role in the pathogenesis of lung fibrosis. In particular, upregulation of IL-6 at the early inflammatory stage of BLM-injured lung has antifibrotic activity through regulating the cell fate of type 2 pneumocytes in an autocrine/paracrine manner.

[A Case of Holmium: YAG Laser Resection of Superficial Bladder Tumor (HoLRBT)].

We present a case of holmium : YAG laser resection of superficial bladder tumor (HoLRBT). A 73-year-old male was referred to our hospital with elevated prostatic specific antigen. Due to difficulty of urination, holmium : YAG laser enucleation of the prostate was performed under the diagnosis of benign prostatic hyperplasia. During the surgery, superficial bladder tumor was incidentally identified, and HoLRBT was performed. After the operation, histopathological examination revealed urothelial carcinoma, G2 ＞ G1, pTa. The patient has been subsequently followed up for 9 months, and there areno evidence of recurrence. Changing the holmium : YAG laser energy setting can potentially be effective and safe to approach a superficial bladder tumor.

[A Case of Emphysematous Pyelonephritis with Pneumoderma Treated by Open Surgical Drainage].

Emphysematous pyelonephritis (EPN) is an acute, severe necrotizing infection of the renal parenchyma and perirenal tissue. A 72-year-old female patient with uncontrolled diabetes mellitus was admitted to a hospital with loss of consciousness and, fever. Laboratory data suggested acute inflammation and hyperosmolar hyperglycemic syndrome. The left EPN was accurately diagnosed after abdominal computed tomographic (CT) scan revealed renal parenchymal gas and fluid within the subcutaneous tissue and mediastinum. The patient was transferred to our institution and underwent emergent open surgical drainage. However, a CT scan performed 3 days after the drainage revealed the presence of fluid in the left perinephric space. CT-guided drainage of the left perinephric fluid was performed. The patient was finally discharged after complete recovery from severe inflammation.

Therapeutic effect of lung mixed culture-derived epithelial cells on lung fibrosis.

Cell-based therapy is recognized as one of potential therapeutic options for lung fibrosis. However, preparing stem/progenitor cells is complicated and not always efficient. Here, we show easily prepared cell populations having therapeutic capacity for lung inflammatory disease that are named as 'lung mixed culture-derived epithelial cells' (LMDECs). LMDECs expressed surfactant protein (SP)-C and gave rise to type I alveolar epithelial cells (AECs) in vitro and in vivo that partly satisfied type II AEC-like characteristics. An intratracheal delivery of not HEK 293 cells but LMDECs to the lung ameliorated bleomycin (BLM)-induced lung injury. A comprehensive analysis of bronchoalveolar fluid by western blot array revealed that LMDEC engraftment could improve the microenvironment in the BLM-instilled lung in association with stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 signaling axis. SDF-1 enhanced both migration activity and differentiating efficiency of LMDECs. Further classification of LMDECs by flow cytometric study showed that a major population of LMDECs (LMDEC(Maj), 84% of total LMDECs) was simultaneously SP-C(+), CD44(+), CD45(+), and hematopoietic cell lineage(+) and that LMDECs included bronchioalveolar stem cells (BASCs) showing SP-C(+)Clara cell secretory protein(+)stem cell antigen (Sca)1(+) as a small population (1.8% of total LMDECs). CD44(+)-sorted LMDEC(Maj) and Sca1(+)-sorted LMDECs equally ameliorated fibrosis induced by BLM like LMDECs did. However, infiltrated neutrophils were observed in Sca1(+)-sorted LMDEC-treated alveoli that was not typical in LMDEC(Maj)- or LMDEC-treated alveoli. These findings suggest that the protective effect of LMDECs against BLM-induced lung injury depends greatly on that of LMDEC(Maj). Furthermore, the cells expressing both alveolar epithelial and hematopoietic cell lineage markers (SP-C(+)CD45(+)) that have characteristics corresponding to LMDEC(Maj) were observed in the alveoli of lung and increased approximately threefold in response to BLM instillation. Taken together, LMDECs newly classified in the present study are easily culture expanded and have a potential role in future regenerative cell therapy for pulmonary fibrosis.

Predictors of benign histology in clinical T1a renal cell carcinoma tumors undergoing partial nephrectomy.

The anatomical characteristics of renal tumors have been classified using several systems. An association between tumor anatomical characteristics and postoperative histological diagnosis can be expected. The present study aimed to assess the rate of and predictive factors for benign histological findings for renal tumors diagnosed as T1a by preoperative imaging. From January 2000 through December 2010, 149 patients underwent partial nephrectomy (either open or laparoscopic) for T1a renal cell carcinoma. The frequency of benign histological findings was evaluated. Logistic regression analysis estimated the relative importance of predictive factors. The overall frequency of benign lesions was 8.1%. Multivariate analysis identified three statistically significant predictive factors for benign lesions: age, sex and exophytic tumor property (P = 0.0356, 0.0183 and 0.0330, respectively). The present findings suggest that exophytic tumors on preoperative imaging are more likely to be benign at histology after partial nephrectomy.

Bone dissemination of prostate cancer after holmium laser enucleation of the prostate: a case report and a review of the literature.

We report a case of dissemination of prostate cancer after holmium laser enucleation of the prostate in an 80-year-old patient. The patient presented at hospital because of nocturia. Transrectal ultrasound-guided biopsy was carried out because of high serum prostate-specific antigen (3.55 ng/mL), but it showed no malignancies. Benign prostate hyperplasia was diagnosed, and he was started on an α1-blocker. Although the urinary symptom improved with silodosin, acute urinary retention occurred 3 years after therapy began. Holmium laser enucleation of the prostate for relief of bladder outlet obstruction enabled discharge of urine. Pathological examination of the resected tissue found adenocarcinoma with a high Gleason score, 4 + 5. Serum alkaline phosphatase increased rapidly after holmium laser enucleation, and bone scintigraphy confirmed multiple bone metastases. Prostate cancer, T1bN0M1b, was diagnosed.

[Investigation of changes in sexual and ejaculatory functions after holmium laser enucleation of the prostate (HoLEP)].

Changes in sexual function and ejaculatory function in patients who had undergone holmium laser enucleation of the prostate (HoLEP) were investigated using questionnaires. In this study, 77 patients on whom HoLEP was performed at our department from July 2010 to December 2010 were included. Of the 77 patients, the number of patients who could achieve an erection increased from 36 (46.8%) preoperatively to 52 (67.5%) postoperatively after HoLEP. Although postoperative ejaculatory dysfunction was found in 38 (73%) of 52 patients, 47 (90%) experienced orgasms, regardless of ejaculation, which is a high rate. With respect to ejaculatory satisfaction, patients who experienced an ejaculation had significantly higher satisfaction levels than those who did not. These results suggest that changes in postoperative ejaculatory function might affect satisfaction levels of ejaculation.

A case of pulmonary tuberculosis that developed during nivolumab and ipilimumab treatment for pulmonary adenocarcinoma that recurred two months after completion of anti-tuberculous treatment.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have become key agents in the treatment of non-small cell lung cancer worldwide. However, immune-related adverse events (irAEs) must be addressed to maximize the efficacy of ICIs. Mycobacterium tuberculosis (Mtb) infection is considered as a type of irAE associated with ICIs, but the underlying mechanism is not completely understood. Here, we present a case of pulmonary tuberculosis (TB) that developed during administration of nivolumab and ipilimumab for pulmonary adenocarcinoma that recurred just 2 months after completion of anti-TB treatment. CASE DESCRIPTION: A 67-year-old man with lung adenocarcinoma was referred to our hospital for chemotherapy. He was a former smoker and had been diagnosed with stage IVA (cT4N1M1a) lung adenocarcinoma. Interferon-gamma release assay (IGRA) yielded positive results at the start of treatment. One month after initiating treatment with nivolumab and ipilimumab, he presented with productive cough and Mtb complex was cultured from sputum samples. Two months after completing anti-TB treatment, recurrence of TB was observed. The series of strains were found to be identical. CONCLUSIONS: This represents the first report of pulmonary TB that developed during nivolumab and ipilimumab treatment, and recurred 2 months after completing anti-TB treatment. Physicians should be mindful of the potential for TB recurrence following the use of ICIs, particularly in patients showing positive results from IGRA.

The impact of real-time 3d imaging by ultra-high speed optical coherence tomography in urothelial carcinoma.

BACKGROUND: Optical coherence tomography (OCT) has become a promising diagnostic tool in many medical fields. In particular, noninvasive real-time optical biopsy of internal organs is one of the most attractive applications of OCT, enabling in situ diagnosis of carcinoma at an early stage. We used an ultra-high speed OCT system for real-time three-dimensional (3D) imaging of three excised specimens of advanced urothelial carcinoma (UC) and investigated the association of the images with results from histopathological examination. CASE PRESENTATIONS: Case 1 was a 69-year-old man underwent radical cystectomy for muscle-invasive UC (pT2). Case 2 was a 53-year-old man underwent laparoscopic nephroureterectomy and partial cystectomy for left ureter carcinoma (pT2) and case 3 was a 77-year-old woman underwent radical cystectomy for advanced bladder carcinoma (pT3b). Real-time 3D OCT images of normal bladder wall and ureter showed three layers, including the urothelium, lamina propria, and muscularis layer. In contrast, normal structure was not seen in the muscle-invasive UC area or the scar tissue area. CONCLUSIONS: This study highlighted a new diagnostic method with potential application for UC diagnosis. We will investigate more cases in the future and expect improvement in the diagnosing efficiency of carcinoma in situ or organ-confined muscle-invasive cancer by cystoscopy or ureteroscopy with ultra-high speed OCT.

Stevens-Johnson syndrome induced by sorafenib for metastatic renal cell carcinoma.

Sorafenib is an orally administered active multikinase inhibitor for metastatic renal cell carcinoma that is now considered a standard agent. Skin toxicity, such as hand-foot skin reaction, is one of the frequent adverse effects of sorafenib. On the other hand, sorafenib-induced erythema multiforme is very rare, and Stevens-Johnson syndrome and toxic epidermal necrolysis induced by sorafenib have not been reported. We report the first case of Stevens-Johnson syndrome caused by sorafenib for metastatic renal cell carcinoma.

[A case of colonic adenocarcinoma incidentally occurring in an Indiana pouch].

We present a rare case of colonic adenocarcinoma occurring in an Indiana pouch. A 68-year-old man underwent radical cystectomy with Indiana pouch urinary diversion for the treatment of bladder cancer 16 years ago. He was referred to our hospital for the treatment of a right staghorn stone, left renal stone, and pouch stones. Cystoscopic findings showed a 10×10 mm tumor distal to ureter anastomosis. Under the diagnosis of colonic adenocarcinoma in an Indiana pouch, tumor and stones were successfully removed. Adenocarcinoma occurrence after ureterosigmoidostomy is well-known. However, diagnosis of adenocarcinoma in an Indiana pouch is extremely rare.