Neuregulin-1-ß1 and γ-secretase play a critical role in sphere-formation and cell survival of urothelial carcinoma cancer stem-like cells.

Previously, we investigated gene expression in a high aldehyde dehydrogenase 1 expression (ALDH1high) population of urothelial carcinoma (UC) cells as UC cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) and found that NRG1 expression was upregulated in ALDH1high cells. NRG1 is a trophic factor that contains an epidermal growth factor (EGF)-like domain that signals by stimulating ERBB receptor tyrosine kinases and the cytoplasmic domain. NRG1 has been determined to be involved in frequent gene fusions with other partners in several malignancies and has a role in carcinogenesis through the NRG1 EGF-like domain and its cognitive receptor ERBBs. We thus aimed to elucidate the function of NRG1 in UC CSCs/CICs in this study. Both NRG1α and NRG1-ß1 were preferentially expressed in ALDH1high cells compared with ALDH1low cells; however, siRNA experiments revealed that NRG1-ß1 but not NRG1-α has a role in sphere formation. The EGF-like domain of NRG1 had a role in sphere formation of UC cells to some extent but was not essential. The intracellular domain of NRG1 did not have a role in sphere-formation. Inhibition of γ-secretase suppressed sphere formation. These findings indicate that cleavage of NRG1-ß1 by γ-secretase plays an important role in UC CSC/CIC proliferation; however, the downstream targets of NRG1-ß1 remain elusive.

Incidence and risk factors of postoperative delirium in elderly patients undergoing urological surgery: A multi-institutional prospective study.

OBJECTIVES: To investigate the incidence and risk factors of postoperative delirium among patients aged ≥65 years undergoing elective urological surgery. METHODS: From April 2015 through December 2016, 1023 consecutive patients aged ≥65 years who received transurethral, laparoscopic (with or without robot assistance) or open surgery in eight institutions were enrolled in this prospective observational study. Their preoperative cognitive status was assessed with the Hasegawa Dementia Scale-Revised score. The treating physician or nurse assessed delirium using the Intensive Care Delirium Screening Checklist. Multivariate logistic regression analysis was used to determine predictive factors for postoperative delirium. RESULTS: We analyzed 946 patients whose median age was 74 years (range 65-95 years). Postoperative delirium was observed in 32 patients (3.4%). Multivariate analysis showed that a history of cerebrovascular disease (odds ratio 5.24, 95% confidence interval 2.05-13.40), low Hasegawa Dementia Scale-Revised score <20 points (odds ratio 3.50, 95% confidence interval 1.36-9.02), low serum albumin level <3.5 g/dL (odds ratio 3.12, 95% confidence interval 1.25-7.83) and long surgery duration >4 h (odds ratio 4.94, 95% confidence interval 2.20-11.10) were independent risk factors for the development of postoperative delirium. CONCLUSIONS: The preoperative medical history, cognitive status, low serum albumin level and operative duration were associated with the development of postoperative delirium, although the incidence was just 3.4% in elective urological surgery. The present results suggest that the Hasegawa Dementia Scale-Revised is a useful tool for assessment of the risk for delirium.

[Dosing Schedules and Outcomes in Patients Treated with First-Line Sunitinib for Advanced Renal Cell Carcinoma].

The objective of this study was to determine whether alternative sunitinib schedules (AS) could prolong survival of patients with advanced renal cell carcinoma (RCC) compared to the traditional 4-weeks-on/2- weeks-off schedule (TS). Between August 2008 and December 2014, 58 patients with advanced RCC were treated with sunitinib. We retrospectively reviewed the records of the patients who received first-line sunitinib. The progression-free survival, overall survival, relative dose intensity and toxicity in the AS and TS groups were compared. A total of 38 patients were included in the analysis. AS was used for 22 patients who started to receive sunitinib beginning in December 2012. For these patients, sunitinib was administered with a 2-weeks-on/1-week-off, 2-weeks-on/2-weeks-off or 2-weeks-on/3-weeks-off schedule according to the adverse events and clinical characteristics of each patient. The median progression-free survival was 5 months (95% CI: 3-7) for TS compared to 12 months (95% CI: 7-17) for AS (p＝0.0020). The median overall survival was 17 months (95% CI: 10-20) for TS compared to 57 months (95% CI: 25-57) for AS (p＝0.0006). There was no significant difference between the TS and AS groups (64% versus 71%). The incidence of Grade ≥3 thrombocytopenia in the AS group was smaller than that in the TS group (44% versus 27%). Treatment with sunitinib using AS may provide a better outcome than that with TS. Prospective, randomized trials should be conducted to confirm this speculation.

CLINICAL FEATURES OF 15 PATIENTS UNDER SURVEILLANCE FOR RENAL MASSES.

(Objective) We investigated the clinical features of patients under surveillance for localized renal masses. (Methods) This study was a retrospective analysis of 15 patients who were diagnosed as having clinically localized renal cell carcinoma and were placed under surveillance and 68 patients who underwent immediate radical operation for renal masses. (Results) The age at diagnosis in the surveillance group was significantly higher than in the immediate operation group (median, 81 vs. 65 years, respectively, P<0.01). The Charlson Comorbidity Index in the surveillance group was significantly higher than in the immediate operation group (median, 5 vs. 2, respectively, P<0.01) and 10 patients (67%) had complications, which was one of the reasons for surveillance. The median initial tumor size in the surveillance group was 2.5 cm (1.5-10.1). There was no significant difference in the tumor size between the two groups. During a median follow-up of 19 months (6-55) the median tumor growth rate was 0.29 cm per year (-0.19-0.65) in the surveillance group. Of the 15 patients with computed tomography follow-up, four underwent surgical resection of the renal masses after surveillance. The histological diagnosis was clear cell renal cell carcinoma in all four. During follow-up, two patients died of other causes and one patient had bone metastasis but there was no death related to the renal masses in the surveillance group. (Conclusions) The appropriateness of the surveillance should be considered when we initiate surveillance for patients with renal masses because metastasis was detected in one patient in this study. On the other hand, surveillance may be an acceptable management method for elderly or severely comorbid patients because there were two deaths from other causes in the surveillance group.

[Prognostic factors and efficacy of molecular targeted therapy for metastatic clear cell renal cell carcinoma].

We retrospectively reviewed the medical records of patients with metastatic clear cell renal cell carcinoma who received molecular targeted therapy between 2005 and 2011. Cancer-specific survival was analyzed using the Kaplan-Meier method. Predictors of cancer-specific survival were analyzed using the Cox regression hazards model. A total of 89 patients, consisting of 50 first line patients and 39 patients receiving prior cytokine were included in the analysis. The two-year cancer-specific survival rate of the firstlinegroup was 60.2% and that of theprior cytokinethe rapy group was 62.1%. In univariateanalysis, Karnofsky performance status (KPS)＜80%, time from diagnosis to treatment less than one year, bone metastasis and C-reactive protein (CRP)＞1.3 mg/dl in were statistically significant prognostic factors (p＜0.05). In multivariate analysis, time from diagnosis to treatment less than one year (HR 2.46, 95%CI 1.11-5.82, p＝0.025) and CRP (HR 4.92, 95%CI 2.23-11.3, p＜0.001) were independent prognostic factors. Time from diagnosis to treatment less than one year and CRP were independent prognostic factors in patients who received molecular targeted therapy.

Prostate cancer stem-like cells/cancer-initiating cells have an autocrine system of hepatocyte growth factor.

Prostate cancer cells include a small population of cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) that have roles in initiation and progression of the cancer. Recently, we isolated prostate CSCs/CICs as aldehyde dehydrogenase 1-highh (ALDH1(high) ) cells using the ALDEFLUOR assay; however, the molecular mechanisms of prostate CSCs/CICs are still elusive. Prostate CSCs/CICs were isolated as ALDH1(high) cells using the ALDEFLUOR assay, and the gene expression profiles were analyzed using a cDNA microarray and RT-PCR. We found that prostate CSCs/CICs expressed higher levels of growth factors including hepatocyte growth factor (HGF). Hepatocyte growth factor protein expression was confirmed by enzyme linked immunosorbent assay and Western blotting. On the other hand, c-MET HGF receptor was expressed in both CSCs/CICs and non-CSCs/CICs at similar levels. Hepatocyte growth factor and the supernatant of myofibloblasts derived from the prostate augmented prostasphere formation in vitro, and prostasphere formation was inhibited by an anti-HGF antibody. Furthermore, c-MET gene knockdown by siRNA inhibited the prostasphere-forming ability in vitro and tumor-initiating ability in vivo. Taken together, the results indicate that HGF secreted by prostate CSCs/CICs and prostate myofibroblasts has a role in the maintenance of prostate CSCs/CICs in an autocrine and paracrine fashion.

Prognostic impact of the expression of ALDH1 and SOX2 in urothelial cancer of the upper urinary tract.

Aldehyde dehydrogenase 1 (ALDH1) and sex determining region-Y-related high mobility group box 2 (SOX2) have been identified as putative cancer stem-like cell/tumor-initiating cell markers in various cancer tissues. The aim of this study was to elucidate the prognostic impact of these putative cancer stem-like cell/tumor-initiating cell markers in upper urinary tract urothelial cell carcinoma. Immunohistochemical staining for ALDH1 and SOX2 was carried out on archival specimens from 125 patients with upper urinary tract urothelial cell carcinoma who underwent radical nephroureterectomy. The prognostic value of ALDH1 and SOX2 expression and other clinicopathological features was evaluated. On univariate analysis, tumor grade, pathological T stage, pathological N stage, lymphovascular invasion, ALDH1 expression and SOX2 expression were associated with a poor prognosis. On multivariate analysis, the independent factors of prognosis were tumor grade (P=0.014), pathological N stage (P=0.005) and ALDH1 expression (P=0.002). In subgroup analysis, those subgroups with no positive, one positive or two positive results in immunohistochemistry for ALDH1 and SOX2 expression had estimated 5-year cancer-specific survival rates of 80%, 49% and 22%, respectively (P<0.001). Neither ALDH1 nor SOX2 expression correlated with intravesical recurrence after radical nephroureterectomy. These findings suggest that cancer stem-like cells/tumor-initiating cells are linked to more aggressive behavior of upper urinary tract urothelial cell carcinoma, supporting the current cancer stem cell hypothesis. Thus, therapeutic targeting of cancer stem-like cells/tumor-initiating cells in upper urinary tract urothelial cell carcinoma is a future possibility.

Potential survival benefit of anti-apoptosis protein: survivin-derived peptide vaccine with and without interferon alpha therapy for patients with advanced or recurrent urothelial cancer--results from phase I clinical trials.

We previously identified a human leukocyte antigen (HLA)-A24-restricted antigenic peptide, survivin-2B80-88, a member of the inhibitor of apoptosis protein family, recognized by CD8+cytotoxic T lymphocytes (CTL). In a phase I clinical trial of survivin-2B80-88 vaccination for metastatic urothelial cancer (MUC), we achieved clinical and immunological responses with safety. Moreover, our previous study indicated that interferon alpha (IFN α ) enhanced the effects of the vaccine for colorectal cancer. Therefore, we started a new phase I clinical trial of survivin-2B80-88 vaccination with IFN α for MUC patients. Twenty-one patients were enrolled and no severe adverse event was observed. HLA-A24/survivin-2B80-88 tetramer analysis and ELISPOT assay revealed a significant increase in the frequency of the peptide-specific CTLs after vaccination in nine patients. Six patients had stable disease. The effects of IFN α on the vaccination were unclear for MUC. Throughout two trials, 30 MUO patients received survivin-2B80-88 vaccination. Patients receiving the vaccination had significantly better overall survival than a comparable control group of MUO patients without vaccination (P = 0.0009). Survivin-2B80-88 vaccination may be a promising therapy for selected patients with MUC refractory to standard chemotherapy. This trial was registered with UMIN00005859.

[Clinical and pathological features of the best candidates for active surveillance-retrospective analysis of patients with radical prostatectomy].

To develop a more clinically relevant protocol and identify the best candidates for active surveillance (AS), we examined the pathological features of radical prostatectomy (RP) specimens of patients who met the Japanese AS protocol criteria. Of 342 patients who underwent RP between 2000 and 2010, 58 (17.0%) eligible for the Japanese AS protocol were retrospectively identified. Pathological features of biopsy specimens and RP specimens were compared to reveal the incidences of up-grading, up-staging and insignificant cancer. We also tried to identify preoperative clinical and pathological factors that accurately predicted the insignificant cancer in the surgical specimens. Up-grading (Gleason score ≥7) and upstaging (≥pT3) were observed in 32 (55.2%) and 6 (10.3%) patients, respectively. Insignificant cancer was observed in 19 (32.8%). Dominant tumors were located in the peripheral zone (PZ) in 34 (58.6%) patients and in the transition zone (TZ) in 24 (41.4%). Multivariate analysis revealed that prostate-specific antigen density ＜0.15 ng/ml/cm3 was a significant independent factor to predict insignificant cancer (odds ratio 6.70, p＝0.036). Larger dominant tumors were associated more frequently with up-grading and up-staging (p=0.038 and p=0.021, respectively), and were more likely to be located in the TZ (P = 0.027). Our results suggest that the risk of up-grading and up-staging should be considered in patients who met the Japanese protocol. Larger dominant tumors were associated more frequently with up-grading and up-staging.

[A case of Crohn's disease developing bladder rupture 4 months after laparoscopic sigmoidectomy with partial cystectomy for vesicosigmoidal fistula].

A 32-year-old well-nourished man having a vesicosigmoidal fistula due to Crohn's disease received laparoscopic sigmoidectomy with partial cystectomy. The bladder wall was closed with an all-layer running suture and additional interrupted sutures using 2-0 Vicryl. Four months after surgery, the suture site on the bladder showed perforation to the abdominal cavity. Since the same event occurred again 6 months after surgery, open partial cystectomy was performed to repair the perforated site 8 months after the initial surgery. The perforated site showed a thinning bladder wall composed of normal urothelium, scar tissue and thin detrusor muscle. Non-caseating granuloma was not found in the specimen, even though it was slightly observed in the margin of the detrusor muscle resected in the initial surgery. Although it was possible that the persisting activity of Crohn's disease, subclinical impaired nutrition due to Crohn's disease or insufficient suturing of the bladder wall were involved in the bladder rupture, the definitive cause remains unknown.

Ureteral calculi secondary to a gradually migrated acupuncture needle.

We herein presented a case of calculi secondary to a migrated acupuncture needle. A 74-year-old woman with a history of acupuncture therapy for lumbago was referred to our hospital for treatment of ureteral and renal pelvic calculi. Abdominal multi-detector computed tomography scans showed ipsilateral hydronephrosis and two calculi secondary to a migrated acupuncture needle. First, a percutaneous nephrolithotomy was performed to extract two calculi and fine needle fragments from the pelvis. Subsequently, residual needle fragments and calculi in the ureter were then removed by flexible transurethral lithotripsy using a holmium laser. In the present case, the formation of the calculi was caused by a migrated acupuncture needle. Calculi and needle fragments were removed safely endoscopically because the whole calculi and needle fragments were located in the ureteral lumen.

[Prognostic factors in patients with metastatic renal cell carcinoma].

To identify prognostic factors for survival and risk classification in Japanese patients, we studied clinical parameters in 79 patients with metastatic renal cell carcinoma (mRCC) treated at our institution from 1988 to 2004. Univariate and multivariate analyses were performed to identify prognostic factors for survival. In univariate analysis, the absence of nephrectomy, metastasis at first visit, ECOG performance status (PS) 2 or more, liver metastasis, brain metastasis, low hemoglobin (0.3, and serum lactate dehydrogenase (LDH) higher than 1.5 times the upper normal limit were significantly associated with poor outcome. Multivariate analysis demonstrated that two variables remained significant : hepatic metastasis and high LDH. Hepatic metastasis, high LDH, nephrectomy, metastasis at first visit, poor ECOG PS and CRP >0.3 were used to categorize patients into three groups. The 2-year survival rate was 72.9% for the patients with no or one risk factor, 40.2% for those with two and 15.1% for those with three or more. According to Motzer's criteria, the 2-year survival rates for patients with favorable risk, intermediate risk, and poor risk were 85.1, 33.0, and 13.1 % respectively. Our prognostic criteria are simple, and can be used to categorize Japanese patients with mRCC into three risk groups.

[Liver metastasis with portal vein tumor thrombosis as a late recurrence of chromophobe renal cell carcinoma].

We report a case of liver metastasis with portal vein tumor thrombosis from chromophobe renal cell carcinoma (RCC). A 62-year-old man was noted to have a wedge-shaped low density area in the liver by computed tomography thirteen years after radical nephrectomy. Hepatic arterioportal shunt was suspected because liver biopsy did not show malignancy. Several months later, the patient showed aggravation of liver function which did not improve regardless of anticoagulant therapy. Recurrent liver biopsy revealed metastatic RCC. Autopsy showed portal vein tumor thrombus from RCC in the liver.

Serum testosterone level is a useful biomarker for determining the optimal treatment for castration-resistant prostate cancer.

OBJECTIVE: Our aim was to evaluate the usefulness of serum testosterone to guide treatment decision for castration-resistant prostate cancer (CRPC). METHODS: We conducted a retrospective analysis of 115 patients with CRPC treated with either abiraterone (n = 43) or enzalutamide (n = 72). A serum testosterone level was measured at time of starting of abiraterone or enzalutamide. We determined whether serum testosterone influenced the outcomes of androgen receptor (AR)-targeted therapy. RESULTS: In the very-low testosterone group (<5 ng/dl), the rate of prostate-specific antigen (PSA) response was significantly higher among patients treated with abiraterone compared to enzalutamide (62 vs. 32%, respectively; P = 0.033), with no difference in the low testosterone group (5-<50 ng/dl) (93 vs. 81%, respectively; P = 0.429). During the median follow-up of 26 months, PSA progression-free survival was significantly longer in the low testosterone group than in the very-low testosterone group (12.2 vs. 4.5 months, P<0.001). In the very-low testosterone group, enzalutamide use (HR 3.07, 95% CI 1.36-6.94; P = 0.007), primary androgen deprivation therapy <12 months (HR 2.50, 95% CI 1.23-5.08; P = 0.011) and bone metastases (HR 2.60, 95% CI 1.20-5.64; P = 0.015) were significantly associated with PSA progression. CONCLUSION: Patients with a serum testosterone level ≥5 ng/dl were more likely to receive therapeutic benefits from AR-targeted therapy compared to those with serum testosterone levels <5 ng/dl. However, even for those with a very low serum testosterone level, the efficacy of abiraterone was slightly higher than that of enzalutamide. Therefore, serum testosterone level is a useful biomarker for informing treatment selection for CRPC.

GRIK2 has a role in the maintenance of urothelial carcinoma stem-like cells, and its expression is associated with poorer prognosis.

Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are small sub-population of cancer cells that are endowed with higher tumor-initiating ability, self-renewal ability and differentiation ability. CSCs/CICs could be isolated as high aldehyde dehydrogenase 1 activity cells (ALDH1high) from various cancer samples. In this study, we isolated urothelial carcinoma CSCs/CICs as ALDHhigh cells and investigated the molecular aspects. ALDH1high cells showed greater sphere-forming ability and higher tumor-initiating ability in immune-deficient mice than those of ALDH1low cells, indicating that CSCs/CICs were enriched in ALDH1high cells. cDNA microarray analysis revealed that an ionotropic glutamate receptor glutamate receptor, ionotropic, kainate 2 (GRIK2) was expressed in ALDH1high cells at a higher level than that in ALDH1low cells. GRIK2 gene knockdown by siRNAs decreased the sphere-forming ability and invasion ability, whereas GRIK2 overexpression increased the sphere-forming ability, invasion ability and tumorigenicity, indicating that GRIK2 has a role in the maintenance of CSCs/CICs. Immunohistochemical staining revealed that higher levels of GRIK2 and ALDH1 expression were related to poorer prognosis in urinary tract carcinoma cases. The findings indicate that GRIK2 has a role in the maintenance of urothelial CSCs/CICs and that GRIK2 and ALDH1 can be prognosis prediction markers for urinary tract carcinomas.

[Hydrodistention of the bladder in patients with interstitial cystitis--clinical efficacy and its association with immunohistochemical findings for bladder tissues].

We retrospectively analyzed the clinical relevance of hydrodistention under anesthesia for patients having urgency and/or lower abdominal pain who were clinically diagnosed as having interstitial cystitis (IC) from May 1996 to May 2005. Their symptoms were refractory to anticholinergic or antiinflammatory agents. Hydrodistention was performed under general or spinal anesthesia with direct vision by cystoscopy and irrigation fluid was instilled into the bladder at a pressure of 80 cmH2O. Cystoscopic findings revealed glomerulation in 26 patients (96%), cracking in 10 (37%) and Hunner's ulcer in 3. Twenty-four patients (89%) obtained improvement of the objective symptoms after treatment. However, symptoms soon deteriorated in 16 patients, and the average duration of efficacy was only 4.7 months (SD; +/-3.7). There were two episodes of complication in this treatment. Bladder rupture occurred during hydrodistention, but was successfully managed with simple percutaneous perivesical drainage. One patient with acute pyelonephritis was treated with an antimicrobial agent without any additional treatment. Although bladder specimens were examined by immunohistochemistry, tryptase and c-kit were not linked with the mast cell count, severity of symptoms or treatment efficacy. Hydrodistention of the bladder may be recommended as the first treatment choice for patients with IC because it provides relatively high efficacy. However, the short duration of the efficacy requires a second-line treatment option for better management of patients with IC.

[Intravesical instillation of resiniferatoxin for the patients with interstitial cystitis].

Although hydrodistention of the bladder is accepted as the initial treatment for patients with interstitial cystitis (IC), second-line treatment for worsening symptoms is not concretely established. Resiniferatoxin (RTX) desensitizes bladder afferent c-fibers and its intravesical instillation is effective for patients with detrusor overactivity. We studied the clinical relevance of intravesical treatment with RTX for patients with IC. The treatment was performed for 3 patients with incomplete improvement after hydrodistention. All 3 patients were free of bladder pain posttreatment and had slight improvement of the maximum voided volume. Though RTX treatment requires general anesthesia against severe bladder pain it is effective for selected patients with interstitial cystitis and can be potentially used as one of the treatment options.

Expression of hepatocyte growth factor in prostate cancer may indicate a biochemical recurrence after radical prostatectomy.

We previously found that prostate cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) express hepatocyte growth factor (HGF) and that the HGF/c-MET proto-oncogene product (c-MET) signal has a role in the maintenance of prostate CSCs/CICs in an autocrine fashion. HGF is, thus, a novel marker for prostate CSCs/CICs. We hypothesized that high expression of HGF might be related to early recurrence of prostate cancer after radical prostatectomy, and the purpose of the present study was to evaluate the relationship between expression of HGF in prostate tissues and biochemical recurrence after radical prostatectomy. One hundred-one patients with prostate cancer who underwent open or laparoscopic radical prostatectomy from November 2008 to October 2011 with an adequate prostate-specific antigen (PSA) follow-up period, were investigated. Immunohistochemical staining of HGF was compared to biochemical recurrence after radical prostatectomy. Patients with tumors exhibiting HGF positivity of 5% or more had a significantly shorter biochemical recurrence-free period than that of patients whose tumor HGF positivity was less than 5% (p=0.001). In multivariate Cox regression, preoperative PSA and HGF positivity were independent predictors of biochemical recurrence following prostatectomy. Our finding suggests a direct link between expression of HGF, a novel prostate marker of CSCs/CICs, and biochemical recurrence after radical prostatectomy in patients with prostate cancer.

Nuclear, but not cytoplasmic, localization of survivin as a negative prognostic factor for survival in upper urinary tract urothelial carcinoma.

Survivin, a member of the inhibitor of apoptosis protein gene family, inhibits apoptosis and promotes mitosis. We determined whether nuclear or cytoplasmic localization of survivin could predict survival of patients with upper urinary tract urothelial carcinoma (UUTUC). Immunohistochemical staining for survivin was carried out on archival specimens from 125 consecutive patients with UUTUC who underwent radical nephroureterectomy. Nuclear and cytoplasmic staining of survivin was scored and compared with clinicopathologic features and cancer-specific survival (CSS). Nuclear expression of survivin was significantly correlated with tumor grade (p < 0.001), lymphovascular invasion (p = 0.022) and poor survival with an estimated 5-year CSS probability of 54 % for tumors with nuclear expression of survivin vs. 73 % for those without nuclear expression of survivin (hazard ratio = 2.19; 95 % confidence interval = 1.02-4.70; p = 0.043). The 5-year cancer-specific survival rates of patients with cytoplasmic survivin-negative and -positive tumors were 66 and 67 %, respectively. There was no difference in survival between patients with cytoplasmic survivin-negative tumors and those with cytoplasmic survivin-positive tumors. Using univariate analysis, nuclear survivin expression, tumor grade, pathological T stage, pathological N stage, and lymphovascular invasion were the predictive variables for CSS. In contrast, cytoplasmic survivin expression had no prognostic relevance. These data suggest that nuclear accumulation of survivin represents biologic aggressiveness and that nuclear survivin is a negative prognostic marker in patients with resected UUTUC.

Pheochromocytoma with abscess.

We report a case of a 34-year-old man who suffered from pheochromocytoma with an abscess in the right adrenal. He presented with a high fever and back pain. He also had some episodes of headache and palpitation. Serum and urine catecholamine levels were elevated. From computed tomography and (123)I-meta-iodobenzylguanidine scans, his condition was diagnosed as pheochromocytoma with an abscess. Two pairs of blood cultures yielded Streptococcus agalactiae, which was believed to be derived from dental caries. He was successfully treated with antibiotics for his abscess and right adrenalectomy for his pheochromocytoma.