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Supplementary Table 1 from Molecular Features of Hormone-Refractory Prostate Cancer Cells by Genome-Wide Gene Expression Profiles

Supplementary Figure 1 Legend from Molecular Features of Hormone-Refractory Prostate Cancer Cells by Genome-Wide Gene Expression Profiles

One of the most critical issues in prostate cancer clinic is emerging hormone-refractory prostate cancers (HRPCs) and their management. Prostate cancer is usually androgen dependent and responds well to androgen ablation therapy. However, at a certain stage, they eventually acquire androgen-independent and more aggressive phenotype and show poor response to any anticancer therapies. To characterize the molecular features of clinical HRPCs, we analyzed gene expression profiles of 25 clinical HRPCs and 10 hormone-sensitive prostate cancers (HSPCs) by genome-wide cDNA microarrays combining with laser microbeam microdissection. An unsupervised hierarchical clustering analysis clearly distinguished expression patterns of HRPC cells from those of HSPC cells. In addition, primary and metastatic HRPCs from three patients were closely clustered regardless of metastatic organs. A supervised analysis and permutation test identified 36 up-regulated genes and 70 down-regulated genes in HRPCs compared with HSPCs (average fold difference > 1.5; P < 0.0001). We observed overexpression of AR, ANLN, and SNRPE and down-regulation of NR4A1, CYP27A1, and HLA-A antigen in HRPC progression. AR overexpression is likely to play a central role of hormone-refractory phenotype, and other genes we identified were considered to be related to more aggressive phenotype of clinical HRPCs, and in fact, knockdown of these overexpressing genes by small interfering RNA resulted in drastic attenuation of prostate cancer cell viability. Our microarray analysis of HRPC cells should provide useful information to understand the molecular mechanism of HRPC progression and to identify molecular targets for development of HRPC treatment. [Cancer Res 2007;67(11):5117–25]

Introduction Trocar site hernia is a potentially serious sequela of laparoscopic procedures that may lead to bowel incarceration and strangulation. We report a case of trocar site hernia secondary to robot-assisted radical prostatectomy. Case presentation A 71-year-old Japanese man underwent robot-assisted radical prostatectomy without any intraoperative events; however, a brief dislodgement of a 12-mm AIRSEAL® trocar occurred. Forty-eight hours after the procedure, the patient exhibited coffee ground vomitus. Computed tomography revealed an intestinal prolapse at the 12-mm AIRSEAL® trocar site. He was diagnosed with a strangulated bowel due to trocar site hernia. Following an emergency exploration, 25 cm of gangrenous intestine was resected, and a functional end-to-end anastomosis was performed. Conclusion In this case, brief dislodgement of the AIRSEAL® trocar may have caused severe subcutaneous emphysema and intestinal sucking. In such situations, certain closure of both, the peritoneum and the fascia, is necessary.

Background Patients with urolithiasis have a lower bone mineral density (BMD) than those without stones, suggesting a potential correlation between calcium stone formation and bone resorption disorders, including osteopenia and osteoporosis. Methods To investigate the influence of BMD on clinical outcomes in urolithiasis, we performed a single-center retrospective cohort study to analyze patients with urolithiasis who underwent both BMD examination and 24-h urine collection between 2006 and 2015. Data from the national cross-sectional surveillance of the Japanese Society on Urolithiasis Research in 2015 were utilized, and additional data related to urinary tract stones were obtained from medical records. The primary outcome was the development of stone-related symptoms and recurrences during follow-up. A total of 370 patients were included in this 10-year study period. Results Half of the patients had recurrent stones, and the two-thirds were symptomatic stone formers. While only 9% of patients had hypercalciuria, 27% and 55% had hyperoxaluria and hypocitraturia, respectively. There was a positive correlation between T-scores and urinary citrate excretion. Both univariate and multivariate analyses demonstrated that female sex was associated with recurrences (odds ratio = 0.44, p = 0.007), whereas a T-score p = 0.037; odds ratio = 0.45, p = 0.01; respectively). Conclusion These results revealed that low T-scores might cause symptoms in patients with urolithiasis, suggesting the importance of BMD examination for high-risk Japanese patients with urolithiasis having hypocitraturia.

Robot-assisted partial nephrectomy is widely performed for small renal masses, achieving excellent perioperative and intermediate oncological outcomes. However, long-term oncological, functional, and quality of life outcomes after robot-assisted partial nephrectomy remain unclear. In this study, we aimed to evaluate quality of life at 1 year and oncological and functional outcomes of robot-assisted partial nephrectomy after a minimum follow-up of 5 years.Personal, perioperative, postoperative, functional, oncological, and quality of life data were evaluated. The EQ-5D-5L tool, which incorporates health profiles and a EuroQol Visual Analog Scale, was used to assess quality of life preoperatively and 365 days postoperatively. Regarding oncological and functional outcomes, overall survival, recurrence-free survival, and changes in estimated glomerular filtration rate were calculated.There were few changes in levels between the two time points for all EQ-5D dimensions. The mean change in EQ-5D-5L was 0.020 (95% confidence interval 0.006-0.033, P = 0.006), and in EuroQol Visual Analog Scale score 4.60 (95% confidence interval 2.17-7.02, P = 0.0003). Overall and recurrence-free survival 5 years after robot-assisted partial nephrectomy were 97.9% and 92.8%, respectively. After an early postoperative decrease, the estimated glomerular filtration rate remained stable over time.Robot-assisted partial nephrectomy in patients with a T1 renal tumor is safe, feasible, and effective from the perspective of quality of life and survival, even after 5 years. When making treatment decisions, perioperative and quality of life outcomes should be considered together with long-term oncological outcomes.

Introduction Hemothorax is a rare but life-threatening complication following mini-endoscopic combined intrarenal surgery. Herein, we describe a patient with left staghorn kidney stone who presented with hemothorax following mini-endoscopic combined intrarenal surgery under ureteroscope-assisted ultrasound-guided access. Case presentation A 47-year-old woman with left staghorn kidney stone underwent mini-endoscopic combined intrarenal surgery, after which she developed shortness of breath. Chest radiography and computed tomography confirmed left hemothorax. Conservative management and left intercostal chest drainage were performed without improvement. Subsequently, video-assisted thoracoscopic debridement was performed. Conclusion Hemothorax is a severe complication of mini-endoscopic combined intrarenal surgery, which, regardless of accurate access through an ideal renal calyx under ureteroscope-assisted ultrasound-guided access, may lead to pleural injury. Refinement of the surgical technique and management after percutaneous nephrolithotomy is the key to avoiding life-threatening situations.

Objectives To elucidate the difference in the lithogenesis of calcium oxalate and calcium phosphate stones. Methods Renal papillary tissues were obtained from 23 idiopathic calcium oxalate and seven calcium phosphate stone patients who had undergone endoscopic lithotripsy. Samples were individually collected from two different regions in each patient: the papillary mucosa containing Randall's plaque and mucosa not containing Randall's plaque. A microarray analysis was carried out on those tissues to compare their gene expression patterns. Furthermore, a causal pathway analysis comparing their differences was carried out. Results Cluster analysis showed that gene expression profiles of calcium phosphate stone patients markedly differed from those of calcium oxalate stone patients. Disease and function analysis showed that Randall's plaque-containing tissues of calcium phosphate stone-forming patients had significantly higher movement and migration of mononuclear leukocytes, and lower tendency toward infection and lymph node formation than Randall's plaque-containing tissues of calcium oxalate stone formers. Additional pathway analysis showed increased immune cell signaling in calcium phosphate formers, such as the helper T cell 1 and 2 pathways, which was confirmed by their messenger ribonucleic acid expression. Conclusions The present results show the upregulation of helper T-cell signaling pathways in Randall's plaque-containing papillae in calcium phosphate, but not in calcium oxalate stone formers. Thus, helper T-cell immune responses and the related inflammatory processes seem to lead to the formation of calcium phosphate stones on Randall's plaques.

Risk assessment for urinary stones has been mainly based on urinary biochemistry. We attempted to identify the risk factors for urinary stones by statistically analyzing urinary biochemical and inflammation-related factors. Male participants (age, 20–79 years) who visited Nagoya City University Hospital were divided into three groups: a control group (n = 48) with no history of stones and two stone groups with calcium oxalate stone experience (first-time group, n = 22; recurring group, n = 40). Using 25-µL spot urine samples, we determined the concentrations of 18 candidate urinary proteins, using multiplex analysis on a MagPix® system. In univariate logistic regression models classifying the control and first-time groups, interleukin (IL)-1a and IL-4 were independent factors, with significantly high areas under the receiver operating characteristic curve (1.00 and 0.87, respectively, P

Background: We previously discovered that renal macrophages (Mφs) phagocytose renal calcium oxalate monohydrate (COM) crystals. This study investigated the processing of engulfed crystals using in vitro models. Methods: J774.1 mouse Mφs were exposed to COM crystals and observed for 24 h using polarized light microscopy with/without cytochalasin B (CB), an inhibitor of phagocytosis, to confirm active crystal phagocytosis. LysoTracker and immunohistochemical staining using transmission electron microscopy for lysosomal-associated membrane protein 1 were used to confirm engulfed COM crystal uptake into lysosomes. Diachronic tracking of specific Mφs was performed to capture the entire course of engulfed COM crystal processing using polarized light microscopy. Follow-up studies of fluorescent COM (f-COM) crystals using imaging cytometry were performed in the presence and absence of nigericin to dissipate the pH gradient in acidic organelles. Results: Phagocytosis rates increased with COM density and were significantly lower in cells treated with CB (p < 0.01). We observed that engulfed crystals colocalized within lysosomes of the Mφs; moreover, diachronic observation indicated that the engulfed COM crystals were subdivided during Mφ division and eliminated by the 7th day of culture. Additionally, imaging cytometry showed that the fluorescence level of f-COM crystals in the nigericin (–) group after 48 h was significantly lower than that in the nigericin (+) group. Conclusions: This study confirmed active phagocytosis and lysosomal processing of engulfed COM crystals by Mφs. This discovery is expected to contribute to the development of future drugs that enhance the COM crystal phagocytic ability of Mφs.

INTRODUCTION AND OBJECTIVE:Renal puncture in endoscopic combined intrarenal surgery (ECIRS) greatly affects success rates and perioperative complications. We developed a method to determine the ide...

Background Robot-assisted radical prostatectomy (RARP) is commonly performed using the transperitoneal (TP) approach with six trocars over an 8-cm distance in the steep Trendelenburg position. In this study, we investigated the feasibility and the benefit of using the extraperitoneal (EP) approach with six trocars over a 4-cm distance in a flat or 5° Trendelenburg position. We also introduced four new steps to the surgical procedure and compared the surgical results and complications between the EP and TP approach using propensity score matching. Methods Between August 2012 and August 2016, 200 consecutive patients without any physical restrictions underwent RARP with the EP approach in a less than 5° Trendelenburg position, and 428 consecutive patients underwent RARP with the TP approach in a steep Trendelenburg position. Four new steps to RARP using the EP approach were developed: 1) arranging six trocars; 2) creating the EP space using laparoscopic forceps; 3) holding the separated prostate in the EP space outside the robotic view; and 4) preventing a postoperative inguinal hernia. Clinicopathological results and complications were compared between the EP and TP approaches using propensity score matching. Propensity scores were calculated for each patient using multivariate logistic regression based on the preoperative covariates. Results All 200 patients safely underwent RARP using the EP approach. The mean volume of estimated blood loss and duration of indwelling urethral catheter use were significantly lower with the EP approach than the TP approach (139.9 vs 184.9 mL, p = 0.03 and 5.6 vs 7.7 days, p

Percutaneous nephrolithotomy (PCNL) is considered to be the first line of treatment for large renal stones. Though PCNL comes with higher morbidity, its efficacy is unbeaten by other minimally invasive modalities. However, potential complications, such as bleeding, occur. Improved skills and modifications of the procedure may reduce the probability of adverse outcomes. This article discusses the current trends and standards in PCNL technique with special focus on all important steps as positioning, access, instruments, dilation, disintegration, and exit, including outcomes, complication management, and training modalities.

Objectives: To evaluate the efficacy of tegafur–uracil (UFT), a prodrug of 5-fluorouracil, plus cisplatin and dexamethasone in patients with docetaxel-refractory prostate cancers. Methods: Twenty-five patients with docetaxel-refractory prostate cancer were administered oral UFT plus intravenous cisplatin (UFT-P therapy) and dexamethasone. Treatment responses were assessed monthly via prostate-specific antigen (PSA) level measurements. Treatment-related adverse events and overall survival were also assessed. Results: UFT-P therapy resulted in decreased PSA levels in 14 (56%) patients and increased PSA levels in 11 (44%). In patients with increased PSA levels, 7 (64%) of the 11 patients displayed decreased PSA doubling times. The UFT-P therapy response rate was 84% (21/25 patients). Imaging studies revealed that tumor shrinkage during UFT-P therapy occurred in 1 patient in whom bilateral hydronephrosis caused by lymph node metastasis improved. The median survival time from docetaxel initiation was 36 months. In UFT-P-treated patients, the median PSA progression and overall survival times were 6 and 14 months, respectively. UFT-P treatment-related adverse events were mild diarrhea, general fatigue, and anorexia. Treatment was not discontinued for any of the patients. UFT-P therapy did not cause serious hepatic or renal dysfunction or pancytopenia. Conclusions: UFT-P therapy is a safe and effective treatment for patients with docetaxel-refractory prostate cancer, although large-scale, multicenter, prospective studies are needed to validate these findings.

INTRODUCTION AND OBJECTIVE:We reported earlier that hands-on training (HOT) significantly improved the SWL success rate from 66.3% to 87.2% at the AUA annual meeting 2012. In this study, we tracked...

INTRODUCTION AND OBJECTIVE:Development of kidney stones has been linked to metabolic syndrome, which is characterized by insulin resistance (IR). In this prospective study, we followed the baseline...

INTRODUCTION AND OBJECTIVES:Partial nephrectomy for endophytic tumor is not only difficult to identify the tumor site but also the risk of positivity surgical margin and prolongation of warm ischem...

INTRODUCTION AND OBJECTIVES:Kidney stone development has been linked to metabolic syndrome (MetS), which is characterized by insulin resistance. In a previous cross-sectional analysis, we reported ...

BACKGROUND Immunoglobulin (Ig) G2 subclass deficiency is known to be associated with recurrent bacterial respiratory infections caused by capsulated bacteria and is found mostly in pediatric patients. However, its impact after allogeneic hematopoietic stem cell transplantation (HSCT) has not been fully assessed. METHODS We retrospectively evaluated the relationship between IgG2 subclass levels and bacterial pneumonia in 74 adult patients who survived longer than 2 years after allogeneic HSCT. RESULTS During the evaluation period, nine patients developed bacterial pneumonia. The median IgG2 level was significantly lower in patients with an infectious episode than in those without (143 mg/dL vs 287 mg/dL; P

Objectives To evaluate the effect of potassium-sodium citrate on the development of computed tomography-detected renal microcalculi into symptomatic stones in calcium stone-forming patients. Methods Patients (aged 20–80 years) with history of calcium component stones who visited Nagoya City Hospital, Nagoya, Aichi, Japan, between April 2009 and June 2014 were included. They were retrospectively divided into those who did not receive potassium-sodium citrate (non-citrate group, n = 157) and those who did (citrate group, n = 60). For patients in both groups, we evaluated blood and urine biochemistry and sediment, number of computed tomography-detected microcalculi, number of asymptomatic microcalculi disappearances, and pain events. Observations were made at study initiation and 12 months later. Results The citrate group showed a significantly increased urine pH (P < 0.001) and daily citrate excretion (P < 0.001) over the study period. The non-citrate group showed increased numbers of microcalculi at study completion (P = 0.002); over the same period, the number of microcalculi in the citrate group decreased significantly (P = 0.03). Additionally, multivariable analysis showed more asymptomatic microcalculi disappearances (odds ratio 2.84, 95% confidence interval 1.49–5.39) and fewer pain events (odds ratio 0.37, 95% confidence interval 0.16–0.72) in the citrate group than in the non-citrate group. A sex-adjusted analysis showed more asymptomatic microcalculi disappearances (odds ratio 3.96, 95% confidence interval 1.57–10.02) and fewer pain events (odds ratio 0.22, 95% confidence interval 0.07–0.70) in women than in men after citrate treatment. Conclusions Potassium-sodium citrate prevents the development of renal microcalculi into symptomatic stones in calcium stone-forming individuals.

An inflammatory myofibroblastic tumor (IMT) is a distinctive neoplasm composed of myofibroblastic and fibroblastic spindle cells, accompanied by inflammatory infiltration of plasma cells, lymphocytes, and eosinophils. IMTs rarely occur in the urinary bladder. It is important to distinguish this tumor from other malignant spindle cell tumors. Herein, we report a patient with an IMT showing muscle invasion, who underwent a transurethral resection of the bladder tumor and, at a later date, partial cystectomy. The resected tumor specimen revealed a proliferation of spindle-shaped cells on a background of plasma cells and lymphocytes. Immunohistochemical staining showed the tumor to be positive for anaplastic lymphoma kinase (ALK), smooth muscle actin, and vascular endothelial growth factor (VEGF). Such histopathological findings were indicative of an IMT, suggesting the use of inhibitors of ALK and VEGF as pharmacotherapy.

Randall plaques (RPs) can contribute to the formation of idiopathic calcium oxalate (CaOx) kidney stones; however, genes related to RP formation have not been identified. We previously reported the potential therapeutic role of osteopontin (OPN) and macrophages in CaOx kidney stone formation, discovered using genome-recombined mice and genome-wide analyses. Here, to characterize the genetic pathogenesis of RPs, we used microarrays and immunohistology to compare gene expression among renal papillary RP and non-RP tissues of 23 CaOx stone formers (SFs) (age- and sex-matched) and normal papillary tissue of seven controls. Transmission electron microscopy showed OPN and collagen expression inside and around RPs, respectively. Cluster analysis revealed that the papillary gene expression of CaOx SFs differed significantly from that of controls. Disease and function analysis of gene expression revealed activation of cellular hyperpolarization, reproductive development, and molecular transport in papillary tissue from RPs and non-RP regions of CaOx SFs. Compared with non-RP tissue, RP tissue showed upregulation (˃2-fold) of LCN2, IL11, PTGS1, GPX3, and MMD and downregulation (0.5-fold) of SLC12A1 and NALCN (P

A 26-year-old man presented with fever, multiple lymphadenopathies, polyclonal hypergammaglobulinemia, and an elevated serum interleukin-6 (IL-6) level. Multicentric Castleman disease (MCD) was diagnosed by lymph node biopsy. Treatment with prednisolone (PSL) was initiated; however, its efficacy was limited. During PSL tapering, rapidly progressive anemia and thrombocytopenia developed concurrently with increased reticulocyte level, elevated serum LDH level, decreased haptoglobin level, and positive direct Coombs test. Based on these findings, Evans syndrome, which is a concurrent development of autoimmune hemolytic anemia and immune thrombocytopenia, was confirmed. The PSL dose was increased but was ineffective. Therefore, treatment with tocilizumab was initiated, and the clinical findings of both MCD and Evans syndrome improved. The clinical course of this case suggests that tocilizumab could be a treatment option for Evans syndrome complicated with MCD. Three other cases of Evans syndrome complicated with MCD have also been reported; however, this is the first case that shows the efficacy of tocilizumab as treatment for both MCD and Evans syndrome.

Background We investigated the impact of postoperative membranous urethral length and other anatomic characteristics of the pelvic floor shape as measured by magnetic resonance imaging on the improvement in continence following robotic-assisted radical prostatectomy. Methods We retrospectively reviewed data from 73 patients who underwent postoperative prostate magnetic resonance imaging following robotic-assisted radical prostatectomy between 2013 and 2018. Patient demographics; pre-, peri-, and post-operative parameters; and pelvic anatomic features on magnetic resonance imaging were reviewed. Patients who used no urinary incontinence pads or pads for protection were considered to have achieved complete continence. Results Urinary continence was restored in 27.4, 53.4, 68.5, and 84.9% of patients at 1, 3, 6, and 12 months after robotic-assisted radical prostatectomy, respectively. When patients were divided into early and late continence groups based on urinary continence at 3 months after robotic-assisted radical prostatectomy, no significantly different clinical characteristics or surgical outcomes were found. However, the mean membranous urethral length (18.5 mm for the early continence group vs. 16.9 mm for the late continence group), levator muscle width (7.1 vs. 6.5 mm, respectively), and bladder neck width on the trigone side (7.2 mm vs. 5.4 mm, respectively) were significantly different between groups (all p p = 0.038) and bladder neck width (odds ratio, 1.585; 95% confidence interval, 1.050–2.393; p = 0.028) were associated with the period of early urinary continence. Conclusions Postoperative membranous urethral length and bladder neck width were significantly associated with early urinary continence recovery after robotic-assisted radical prostatectomy. It is highly recommended that surgeons focus on preserving the membranous urethral length and increasing the bladder neck width on the trigone side during surgery to achieve optimal continence outcomes after robotic-assisted radical prostatectomy.

The clinical need for platelet transfusions is increasing; however, donor-dependent platelet transfusions are associated with practical problems, such as the limited supply and the risk of infection. Thus, we developed a manufacturing system for platelets from a donor-independent cell source: a human adipose-derived mesenchymal stromal/stem cell line (ASCL). The ASCL was obtained using an upside-down culture flask method and satisfied the minimal criteria for defining mesenchymal stem cells (MSCs) by The International Society for Cellular Therapy. The ASCL showed its proliferation capacity for ≥2 months without any abnormal karyotypes. The ASCL was cultured in megakaryocyte induction media. ASCL-derived megakaryocytes were obtained, with a peak at day 8 of culture, and ASCL-derived platelets (ASCL-PLTs) were obtained, with a peak at day 12 of culture. We observed that CD42b+ cells expressed an MSC marker (CD90) which is related to cell adhesion. Compared with peripheral platelets, ASCL-PLTs exhibit higher levels of PAC1 binding, P-selectin surface exposure, ristocetin-induced platelet aggregation, and ADP-induced platelet aggregation, as well as similar levels of fibrinogen binding and collagen-induced platelet aggregation. ASCL-PLTs have lower epinephrine-induced platelet aggregation. The pattern of in vivo kinetics after infusion into irradiated immunodeficient NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ mice was similar to that of platelet concentrates. ASCL-PLTs have similar characteristics to those of peripheral platelets and might have an additional function as MSCs. The establishment of the ASCL and its differentiation into ASCL-PLTs do not require gene transfer, and endogenous thrombopoietin is used for differentiation. The present protocol is a simple method that does not require feeder cells, further enhancing the clinical application of our approach.