Sunitinib-related high-grade proteinuria and allograft dysfunction in a kidney recipient: a rare case report.

BACKGROUND: Sunitinib-induced high-grade proteinuria and irreversible renal allograft dysfunction are rare conditions. Here, we present a patient who had received renal allograft and later developed metastatic clear cell renal cell carcinoma(cc-mRCC), for which he was prescribed sunitinib. High-grade proteinuria, hypoalbuminemia, peripheral edema and renal allograft dysfunction (manifesting as an increase in the serum creatinine concentration) occurred 5 months after sunitinib prescription. CASE PRESENTATION: The patient was a 58-year-old male who had end-stage renal disease with regular hemodialysis through arteriovenous fistula for 17 years since 1998 and received a renal allograft from a deceased kidney donor in 2015. Unfortunately, in 2019, the patient developed cc-mRCC originating from the left native kidney. We suggested a needle biopsy on left native kidney or radical left nephrectomy, but the patient refused. Sunitinib was prescribed. Follow-up urine analysis showed proteinuria (500 mg/dL) 2 weeks after sunitinib prescription. He was hospitalized 5 months later because of body weight gain, decreased urine output, pitting edema of both lower extremities, and shortness of breath. The image studies showed progression in his cc-mRCC. His serum creatinine level and spot urine protein at admission increased to 4.26 mg/dL and 300 mg/dL, respectively. He agreed on a biopsy for the renal allograft and the pathology studies showed focal segmental glomerulosclerosis, acute interstitial nephritis, and acute tubular injury. Based on the time sequence of clinical presentations with the laboratory and pathological findings, sunitinib-induced renal allograft dysfunction secondary to high-grade proteinuria was most likely. Despite of discontinuation of sunitinib and increased dose of everolimus, renal impairment progressed. Thus, he had to receive hemodialysis starting 2 week after hospitalization. Unfortunately, the patient died of advanced metastasis despite of aggressive medical treatments 3 weeks after admission. CONCLUSION: This case report is a reminder that renal allograft dysfunction can happen secondary to proteinuria after taking sunitinib. Hence, clinicians must regularly check renal function and urine protein for renal allograft recipients. Monitoring and modifying drug prescription, especially sunitinib, is necessary if persistent proteinuria accompanied by deteriorating serum creatinine level occurs. Renal biopsy may be considered if more evidence is required to make a differential diagnosis.

The high incidence of JC virus infection in urothelial carcinoma tissue in Taiwan.

Human polyomaviruses, JC virus (JCV) and BK virus (BKV), usually remain latent in kidney and urothelial tissue after primary infection. Infection with human polyomavirus has still not been correlated conclusively with malignancy of kidney and urothelial tissue. The present study investigated further the possible relationship between JCV/BKV infection and urothelial carcinoma. Tissue samples were examined from 33 urothelial carcinomas and 5 renal cell carcinomas for JCV/BKV infection, using nested PCR with primers common to both JCV and BKV. The viral genotypes were further verified by endonuclease digestion and DNA sequencing following the PCR. In addition, immunohistochemistry and Western blotting were also performed to detect viral large tumor protein (LT) and the late capsid protein (VP1) in the tissue samples. The results from nested PCR showed that 90.1% (30/33) of the urothelial carcinomas samples and all of the renal cell carcinomas samples (5/5) were JCV DNA positive. Both archetypal and re-arranged JCV genotypes were detected. On the other hand, BKV DNA was detected in only one (3%) of the urothelial carcinoma tissue samples. The immunohistochemical results showed that 30% (10/33) of urothelial carcinoma tissues was stained positive for large tumor antigen (LT). However, the structural protein VP1 was not detectable in any of the tissue samples examined. The present study demonstrated that JCV is highly prevalent in urothelial carcinoma tissue as is the expression of large tumor antigen. Therefore, the findings support the hypothesis that JCV infection is associated with urothelial carcinoma.

Safety and efficacy of tubeless percutaneous nephrolithotomy in patients on anti-platelet therapy and cirrhotic patients.

Without the temponade effect over nephrostomy tube, postoperative hemorrhage is a major concern to the safety of tubeless percutaneous nephrolithotomy (PCNL) in patients with bleeding tendency. In this study, we would like to report our experience of performing tubeless PCNLs in these patients. At the end of PCNL, we cauterized the bleeding points in access tract for hemostasis to facilitate the achievement of tubeless PCNL. We identified and reviewed 16 patients under antiplatelet agent therapy and 6 patients with liver cirrhosis from 598 tubeless PCNLs performed in a single institute. Among the 16 patients undergoing anti-platelet therapy, the average stone size was 2.8 cm. The average operation time was 84.7 min. The stone-free rate was 87.5%. The average postoperative hospital stay was 3.8 days. Two patients (12.5%) experienced urinary tract infections after operation. There was no uncontrolled hemorrhage during and after operation and only one patient needed postoperative blood transfusion. No patient experienced any thromboembolic complication. Of the six patients with liver cirrhosis, the average stone size was 3.3 cm. The average operation time was 77.5 min. The stone-free rate is 83.4%. The average postoperative hospital stay was 4.0 days. No patient received blood transfusion after operation. There was no patient experiencing urinary tract infection after operation. Our results suggest that with careful hemostasis, tubeless PCNL is a safety modality in the treatment of urinary stone disease in patients on chronic anti-platelet therapy and cirrhotic patients.

The correlation between TWIST, E-cadherin, and beta-catenin in human bladder cancer.

PURPOSE: Epithelial-to-mesenchymal transition (EMT)- related factors are known to contribute to the invasion and migration of multiple cancers. However, the expression levels of and the relationship between TWIST, E-cadherin, and beta-catenin in bladder cancer are not yet known. Therefore, this study investigated the relationship between TWIST, E-cadherin, and beta-catenin in tissue specimens and cell lines of bladder cancer. METHODS: Microarrays of bladder cancer tissue and bladder cancer cell lines were used to study the expression levels of TWIST, E-cadherin, and beta-catenin, with disease stage and grade using immunohistochemistry. Moreover, the siRNAs of TWIST, E-cadherin, and beta-catenin were transfected into the bladder cancer cell lines to study any relationship between these factors. RESULTS: The levels of TWIST and beta-catenin were upregulated with increasing grade of malignancy. In contrast, the corresponding results for E-cadherin were just the opposite. Furthermore, inhibition of the expression of TWIST elevated the expression of E-cadherin, but reduced the expression of beta-catenin. However, reduction of beta-catenin by siRNA had no influence on TWIST, but up-regulated the expression of E-cadherin. CONCLUSION: TWIST may act upstream of E-cadherin, which can indirectly regulate the expression levels of beta-catenin. The EMT factors TWIST, E-cadherin, and beta-catenin may be a cluster of biomarkers for the metastatic progression of bladder cancer.

Analysis of the effects of cyproheptadine on bladder cancer through big data.

This study was designed to compare the efficacy of Cyproheptadine (CY) in patients with bladder cancer (BC) who received different therapeutic modalities. We used the database from a hospital in Taiwan for analysis. We included patients diagnosed as having bladder cancer from January 1, 2008, to December 31, 2017. The patient cohort comprised those who received different treatments, and we compared patients who received CY with those who did not. In total, 627 patients were included, and the mean follow-up duration was 3.26 years. All data were filtered out by 230 million data and 119 patients had used CY. Among them, 32 patients were used over 3 months of CY. The CY treatment curve shown by Kaplan-Meier survival curves for patients treated is higher than that of the non-CY effect. The value of Chi-squared statistic was 4.138 with associated p-value less than 0.05. Two survival curves shown by the result of the log rank test differ significantly. The grouping variable different treatments for non-CY and CY has a significant influence on survival rate. These results suggest that the use of CY may improve the survival rate of patients with BC.

Needle Tip Culture after Prostate Biopsy: A Tool for Early Detection for Antibiotics Selection in Cases of Post-Biopsy Infection.

PURPOSE: To investigate biopsy needle tip culture after prostate biopsies for bacteria prediction and antibiotics selection. MATERIALS AND METHODS: From May 2017 to April 2019, 121 patients who underwent a prostate biopsy were enrolled. All biopsy needle tips were sent for aerobic and anaerobic culture. Patients were divided into positive and negative culture groups. Perioperative data were recorded and compared between the two groups. The culture time and susceptibility of febrile patients were analyzed. Blood cultures were conducted for all patients who experienced fever after biopsy. The time and results of the needle and blood cultures were recoded for descriptive analysis. RESULTS: There were 59 (48.8%) positive needle cultures. Other than fever (p = 0.023), there were no statistical significances in clinical data between the two groups. Fever occurred in eight patients, and seven febrile patients had positive needle cultures, six of whom had positive blood cultures. These six needle and blood cultures were consistent with the susceptibility test results. As compared to the waiting time for blood cultures, target antibiotics were administered at an average of 48.0 h earlier based on needle cultures. None of the patients with positive anaerobic cultures developed a fever, while all eight febrile patients had negative anaerobic cultures. CONCLUSION: Fevers developed at statistically significant higher rate among those who had positive needle cultures. Needle and blood cultures were consistent with the susceptibility test results. Needle cultures can help us administer target antibiotics earlier to febrile patients without the need to wait for blood cultures.

The aggressiveness of urinary tract urothelial carcinoma increases with the severity of chronic kidney disease.

OBJECTIVE: To assess, in a retrospective cohort, urinary tract urothelial carcinoma (UT-UC) in patients with various stages of chronic kidney disease (CKD) and their clinicopathological features, as patients with end-stage renal disease (ESRD) have a higher incidence of UT-UC, but the relationship between early stages of CKD and characteristics of UT-UC are less well known. PATIENTS AND METHODS: The study included 267 patients with pathologically confirmed UT-UC from January 1994 to December 2006; all had a physical examination (blood pressure), and measurements of laboratory data (serum creatinine, serum haemoglobin) and pathological data. The glomerular filtration rate (GFR) was calculated using the Modification of Diet in Renal Disease equation. Patients were divided into three groups by individual GFR (mL/min), i.e. >60 (no/mild CKD), 30-60 (CKD stage 3) and <30 (CKD stage 4/5). RESULTS: The CKD stages included 81 (30.3%) patients with none/mild CKD, 121 (45.3%) with CKD stage 3 and 65 (24.3%) with CKD stage 4/5. There was a significant and parallel increase in the frequency of UT-UC as CKD severity increased from none/mild CKD to stage 3 (11% vs 55%), and from CKD stage 3 to 4/5 (55% vs 71%; P < 0.05). Pathologically, the frequency of high-grade and high T stage UT-UC in patients with CKD stage 3 (90% and 35%, respectively) and CKD stage 4/5 (91% and 29%, respectively) were significantly greater than in the group with none/mild CKD (P < 0.001). Advanced age and more distant metastasis were independent risk factors for patient survival. CONCLUSION: The aggressiveness of UT-UC increased with the severity of CKD, and this might have important clinical consequences.

Tubeless percutaneous nephrolithotomy for geriatric patients.

AIM: To evaluate the safety of tubeless percutaneous nephrolithotomy (PCNL) in geriatric patients. MATERIALS AND METHOD: This is a retrospective review of 401 patients who received tubeless PCNL in a single institute. Among these, 50 were performed in patients aged older than 70 years (group 1), while 351 were performed in the remaining younger patients (group 2). RESULTS: There was no significant difference in stone size between the 2 groups (3.6 +/- 1.9 vs. 3.5 +/- 2.0 cm). The average operative time was similar in both groups (92.8 +/- 34.5 vs. 86.6 +/- 32.0 min). The stone-free rate in groups 1 and 2 was 68.0% (34/50) and 83.8% (294/351), respectively, which was statistically significantly different. The average postoperative hospital stay was longer in group 1 (4.6 +/- 3.4 days) than in group 2 (3.9 +/- 2.5 days), but the difference was not statistically significant. There was no significant difference in postoperative urinary tract infection rate and blood transfusion rate in both groups (urinary tract infection: 18.0 vs. 8.8%; blood transfusion: 4 vs. 2.6%). Two patients in group 1 and 3 patients in group 2 experienced pulmonary complications. There was no other severe complication. CONCLUSION: Tubeless PCNL is a safe procedure for the treatment of geriatric patients with urolithiasis.

History of Urinary Retention Is a Risk Factor for Infection after Prostate Biopsy: A Nationwide, Population-Based Cohort Study.

BACKGROUND AND AIM: Infection or bleeding after transrectal prostate biopsy remains a concern of both patients and urologists. We explored the risk of association of certain co-morbidities with both complications. PATIENTS AND METHODS: Using the Taiwan National Health Insurance Research Database, we identified patients undergoing prostate biopsy from 2000 to 2013. We used logistic multivariable regression to search for associations between post-biopsy hospitalization and the two co-morbidities within a year after biopsy. RESULTS: Among 3,601 prostate biopsies, 100 infections (3.77%) and 52 (1.44%) bleeding-related emergency room visits and hospitalizations were recorded within 30 days after biopsy. The group having the biopsy as an inpatient exhibited older age (p < 0.0001) and a higher percentage of having diabetes mellitus (p = 0.015) than patients without either complication. The logistic multivariable regression analysis showed that urinary retention, freedom from diabetes, and performance as an outpatient procedure were independent risk factors for infection-related hospitalization (odds ratios 1.81, 1.96, and 1.72; p values 0.031, 0.037, and 0.010, respectively). CONCLUSION: Patients with a recent history of urinary retention have a higher probability of infection-related hospitalization after prostate biopsy.

Hyperbaric oxygen therapy for cyclophosphamide-induced intractable refractory hemorrhagic cystitis in a systemic lupus erythematosus patient.

Hemorrhagic cystitis is a complication of systemic lupus erythematosus and is also a common side effect after cyclophosphamide therapy. Intractable hemorrhagic cystitis is not unusual and may be a life-threatening condition; it has no effective noninvasive treatment at present. We report a case of hemorrhagic cystitis with intractable refractory bleeding that occurred in a 40-year-old woman after cyclophosphamide treatment for systemic lupus erythematosus. The hemorrhage was resistant to various therapies but resolved after hyperbaric oxygen therapy. There was no recurrent hematuria after hyperbaric oxygen therapy during 6 months of follow-up.

Delayed pneumothorax after tubeless percutaneous nephrolithotomy.

Percutaneous nephrolithotomy is the treatment of choice for large urinary stone and staghorn stone. Supracostal access through the upper calyx provides a straight tract along the long axis of the kidney and is the optimal route for the treatment of staghorn stone. However, the supracostal access bears higher risk for pleural or lung injury resulting in hydrothorax or pneumothorax. Percutaneous nephrolithotomy induced pneumothorax usually occurs immediately after operation. We report a case of delayed pneumothorax after tubeless percutaneous nephrolithotomy for a complete staghorn stone.

Evaluation of urinary bladder fibrogenesis in a mouse model of long-term ketamine injection.

Long-term ketamine abuse has been shown to affect the lower urinary tract and result in interstitial cystitis-like syndrome. However, the causative mechanism of ketamine-induced dysfunction remains unclear. The present study aimed to investigate the physiological, histological and molecular changes on ketamine­associated cystitis (KC) in a mouse model. Both male and female Balb/c mice were separately distributed into the control group (normal saline) and ketamine group, which received ketamine hydrochloride (100 mg/kg/day) daily by intraperitoneal injection for a total period of 20 weeks. In each group, the urine was analyzed by gas chromatography­mass spectrometry to measure the concentration of ketamine and its metabolites. Urinary frequency and urine volume were examined to investigate the urinary voiding functions. Mice bladders were excised for cDNA microarray and hematoxylin and eosin (HE) staining. The ketamine and metabolites were detected only in ketamine­treated mice urine. The voiding interval was reduced in the male mice group after 20 week ketamine administration. Additionally, the result of cDNA array analysis revealed a number of gene expression levels involved in chronic wound healing response and collagen accumulation, which were closely associated with fibrosis progression in the connective tissue. In HE staining of the bladder tissue, the ketamine-injected mice exhibited prominently denser blood vessel distribution in the submucosal layer. Based on the evidence in the present study, a mechanism that delineates fibrosis formation of urinary bladder induced by the pathogenesis of ketamine abuse can be constructed.

Foxp3 enhances HIF-1α target gene expression in human bladder cancer through decreasing its ubiquitin-proteasomal degradation.

Hypoxia-inducible factor-1α (HIF-1α) can control a transcriptional factor forkhead box P3 (Foxp3) protein expression in T lymphocyte differentiation through proteasome-mediated degradation. In this study, we unveil a reverse regulatory mechanism contributing to bladder cancer progression; Foxp3 expression attenuates HIF-1α degradation. We first demonstrated that Foxp3 expression positively correlates with the metastatic potential in T24 cells and can increase the expression of HIF-1α-target genes, such as vascular endothelial growth factor (VEGF) and glucose transporter (GLUT). Foxp3 protein can bind with HIF-1α, particularly under hypoxia. In vivo ubiquination assay demonstrated that Foxp3 can decrease HIF-1α degradation in a dose-dependent manner. Knocking-down of Foxp3 expression blocks in vivo tumor growth in mice and prolongs mice's survival, which is associated with von Willebrand factor expression. Thirty-three of 145 (22.8 %) bladder tumors exhibit Foxp3 expression. Foxp3 expression is an independent predictor for disease progression in superficial bladder cancer patients (p = 0.032), associated with less number of intratumoral CD8+ lymphocyte. The metaanalysis from 2 published datasets showed Foxp3 expression is positively associated with GLUT-4,-9, and VEGF-A, B-, D expression. This reverse post-translational regulation of HIF-1α protein by Foxp3 provides a new potential target for developing new therapeutic strategy for bladder cancer.

Methylomics analysis identifies ZNF671 as an epigenetically repressed novel tumor suppressor and a potential non-invasive biomarker for the detection of urothelial carcinoma.

The molecular mechanism underlying the lethal phenomenon of urothelial carcinoma (UC) tumor recurrence remains unresolved. Here, by methylation microarray, we identified promoter methylation of the zinc-finger protein gene, ZNF671 in bladder UC tumor tissue samples, a finding that was independently validated by bisulphite pyrosequencing in cell lines and tissue samples. Subsequent assays including treatment with epigenetic depressive agents and in vitro methylation showed ZNF671 methylation to result in its transcriptional repression. ZNF671 re-expression in UC cell lines, via ectopic expression, inhibited tumor growth and invasion, in possible conjunction with downregulation of cancer stem cell markers (c-KIT, NANOG, OCT4). Clinically, high ZNF671 methylation in UC tumor tissues (n=96; 63 bladder, 33 upper urinary tract) associated with tumor grade and poor locoregional disease-free survival. Quantitative MSP analysis in a training (n=97) and test (n=61) sets of voided urine samples from bladder UC patients revealed a sensitivity and specificity of 42%-48% and 89%-92.8%, respectively, for UC cancer detection. Moreover, combining DNA methylation of ZNF671 and 2 other genes (IRF8 and sFRP1) further increased the sensitivity to 96.2%, suggesting a possible three-gene UC biomarker. In summary, ZNF671, an epigenetically silenced novel tumor suppressor, represents a potential predictor for UC relapse and non-invasive biomarker that could assist in UC clinical decision-making.

Cauterization of access tract for nephrostomy tube-free percutaneous nephrolithotomy.

BACKGROUND AND PURPOSE: Percutaneous nephrolithotomy (PCNL) is now a popular method for removal of renal and ureteral stones. Placement of a nephrostomy tube after the completion of PCNL has been considered a standard procedure by most urologists, but some authors have recently challenged this practice. Bleeding is one of the most prevalent problems after nephrostomy tube-free percutaneous renal surgery. To diminish the possibility of postoperative bleeding, we cauterized the PCNL tract to make it bloodless. The efficacy and safety of this procedure were reviewed in this study. PATIENTS AND METHODS: From March 2001 to March 2003, 51 patients underwent PCNL with a one-stage procedure and a single access tract. The stone size ranged from 1.0 to 7.0 cm (mean 2.7 +/- 1.4 cm). A holmium:YAG laser and pneumatic lithotripter were used. After stone extraction, a 6F double-J catheter was inserted antegrade. The access tract was checked, and the bleeding points were cauterized. No nephrostomy tube was inserted, but a Penrose drain was left overnight. Perforation of the collecting system was not a contraindication to tubeless PCNL. RESULTS: The stone-free rate was 80.4%, including five patients with complete staghorn stones. Twenty-one patients required postoperative analgesics. Only one patient had urine leakage for longer than 24 hours. Transient low fever was noted in five patients, but no patient experienced severe urinary tract infection. Delayed hemorrhage (1 week after the operation) secondary to irritation by the double-J ureteral stent was noted in one patient. The average postoperative hospital stay was 2.2 days (range 1-3 days). No patient required a blood transfusion. No urinoma was noted on the postoperative ultrasound follow-up. CONCLUSION: Nephrostomy tube-free percutaneous renal surgery is a safe and effective procedure for selected patients with minimal hemorrhage after PCNL. Cauterization of tract bleeding points may make this modification a more secure procedure and make it suitable for more patients.

Loss of nuclear prothymosin-α expression is associated with disease progression in human superficial bladder cancer.

In this paper, we report a study on the clinical relevance of prothymosin-α expression and its correlation with intratumoral Foxp3(+) and CD8(+) lymphocytes (Foxp3(+)TIL and CD8(+)TIL) in bladder cancer patients. We used immunohistochemical staining for prothymosin-α, Foxp3, and CD8 on 101 tumor specimens harvested by endoscopic resection. The results were correlated with clinicopathological variables and clinical outcome in bladder cancer patients, particularly in 73 patients with superficial disease, using the log-rank test and Cox proportional hazard model. Overall, of the tumors, 30 % were negative, 34 % showed nuclear, and 37 % showed cytoplasmic prothymosin-α expression. Foxp3(+)TILs were detected in 11 % of patients (nonnuclear vs. nuclear, p = 0.096). Patients with a history of urothelial carcinoma have a higher frequency of nonnuclear prothymosin-α expression than those without (p = 0.016, chi-square test). By univariate and multivariate analyses of cases with superficial disease, grade and stage were identified as independent predictors for recurrence-free survival (p = 0.016 and 0.016, respectively). Higher stage and nonnuclear prothymosin-α expression independently predict shorter progression-free survival (p = 0.006 and 0.043, respectively). The presence of Foxp3(+)TILs was significantly associated with disease progression by univariate analysis (p = 0.022), but not by multivariate analysis (p = 0.147). In vitro assays showed that J82 cells which express ectopically nuclear prothymosin-α exhibit higher growth rate and secrete less TGF-ß1 than those with cytoplasmic expression or control cells. Altogether, prothymosin-α expression is a determinant of disease progression in superficial bladder cancer. Foxp3(+)TILs tend to be found more often in bladder cancer with nonnuclear prothymosin-α expression. Future study is required to unravel their interaction.

Prognostic relevance of preoperative circulating CD8-positive lymphocytes in the urinary bladder recurrence of urothelial carcinoma.

OBJECTIVE: Tumor-infiltrate lymphocytes (TIL) have been associated with favorable outcomes in various tumors including urothelial carcinoma (UC). There is little literature about peripheral blood lymphocytes (PBL). Our objective is to investigate the clinical significance and relevance of PBL on the outcomes of UC patients. MATERIALS AND METHODS: Ninety UC treated patients at Chia-Yi Christian hospital were enrolled. Preoperative PBLs were collected and analyzed for the percentage of each subpopulation of lymphocyte using flow cytometry. The prognostic values were calculated by using Kaplan-Meier curve and Cox progression model for univariate and multivariate analyses, respectively. Furthermore, available tumor specimens from 27 patients were further analyzed for number of CD8(+) tumor infiltrating lymphocytes (TIL) using immunohistochemistry. The correlation between percentage of CD8+ PBL and number of CD8+ TIL was analyzed using a linear regression model. RESULTS: The log-rank test showed that tumor location (urinary bladder vs. upper urinary tract), enrolled status (primary or recurrent), and CD8(+) PBL were significant prognostic indicators of recurrence (P values, 0.043, 0.039, and 0.018, respectively). Cox analyses showed that CD8(+) PBL was the sole independent prognostic indicator for recurrence-free survival (P = 0.048). The results using a linear regression analysis showed there was a reverse correlation between CD8(+) TIL and PBL (r(2) = 0.635, P < 0.0001). CONCLUSIONS: In our investigation, preoperative CD8(+) PBL was an independent predictor for bladder recurrence. The percentages of CD8(+) PBL were reversely correlated with the number of TIL. Such findings may benefit in the decision for subsequent intravesical therapy after surgery.

Bilateral ureteral complete obstruction with huge spontaneous urinoma formation in a patient with advanced bladder cancer.

Spontaneous rupture of the collecting system with extravasation of urine and urinoma formation is usually associated with urinary tract obstruction by a ureteral calculus. Tumor growth is an extremely rare cause of urinary extravasation. Here we report a case of bilateral obstructive uropathy with a huge spontaneous left retroperitoneal urinoma caused by advanced infiltrative transitional cell carcinoma of the urinary bladder. The point of leakage was located in the left renal pelvis. The urinary leakage ceased after percutaneous nephrostomy drainage, and the patient subsequently underwent radical cystoprostatectomy. Histopathology revealed a high-grade urothelial carcinoma of the urinary bladder with pelvic lymph node metastasis. The patient refused any adjuvant treatment and expired 6 months after the operation from disseminated metastasis from bladder cancer.

Dysfunction of natural killer cells in patients with transitional cell carcinoma.

Previous studies had established that transforming growth factor-beta1 (TGF-beta1) is highly expressed in bladder tumor, facilitating progression and spreading of the cancerous cells. Here, we report that both the number and the cytotoxic function of natural killer (NK) cells are decreased in patients with superficial transitional cell carcinoma (TCC). In consistent with previously reported findings, the plasma TGF-beta1 concentration is also elevated in patients with superficial TCC. In vitro, the cytotoxic function of NK cells was impaired by the presence of TGF-beta1. Hence, our data suggested elevated concentration of serum TGF-beta1 in loss of NK cytotoxicity in superficial TCC patients, implicating altered innate immunity may correlate with the incidence of TCC.

High Dickkopf-1 expression is associated with poor prognosis in patients with advanced urothelial carcinoma.

Although Dickkopf-1 (DKK1) has been demonstrated to be associated with tumorigenesis in various types of human tumors, a correlation between DKK1 and urothelial carcinoma (UC) has not been reported. In the present study, the correlation between DKK1 expression and UC progression was investigated. Seventy-five UC patients were enrolled. The expression of DKK1 in serum and UC tissue was detected by ELISA, real-time PCR and Western blotting. Prognostic significance was assessed by using Kaplan-Meier survival estimates and log-rank tests. The results showed that serum levels of DKK1 were significantly higher in the UC patients with muscle-invasive (p=0.0001) and high-grade tumors (p=0.00001) as compared to the controls. A high-serum DKK1 was also associated with poor disease-free survival in the UC patients (hazard ratio=2.44; 95% CI 1.10-5.40; p=0.028). Furthermore, DKK1 was also overexpressed in 93% (41/44) of the UC tissues. Therefore, the findings indicate that the expression of DKK1 is associated with UC progression.