Complete genome sequence of "Bacillaceae sp. strain IKA-2": a cold-active, amylase-producing bacterium from ikaite columns in SW Greenland.

Bacillaceae sp. strain IKA-2 is a bacterium isolated from the permanently cold and alkaline ikaite columns in the Ikka Fjord in SW Greenland (61°12'05″N; 48°00'50″W). The bacterium grows well at 10°C in a substrate buffered to pH 10. It has a genome size of 4,424,890 bp and a guanine-cytosine (GC) content of 36.2%. The genome harbors genes involved in hydrolysis of long carbohydrates and in protection against cold shock.

Mycoheterotrophic Epirixanthes (Polygalaceae) has a typical angiosperm mitogenome but unorthodox plastid genomes.

BACKGROUND AND AIMS: Fully mycoheterotrophic plants derive carbon and other nutrients from root-associated fungi and have lost the ability to photosynthesize. While mycoheterotroph plastomes are often degraded compared with green plants, the effect of this unusual symbiosis on mitochondrial genome evolution is unknown. By providing the first complete organelle genome data from Polygalaceae, one of only three eudicot families that developed mycoheterotrophy, we explore how both organellar genomes evolved after loss of photosynthesis. METHODS: We sequenced and assembled four complete plastid genomes and a mitochondrial genome from species of Polygalaceae, focusing on non-photosynthetic Epirixanthes. We compared these genomes with those of other mycoheterotroph and parasitic plant lineages, and assessed whether organelle genes in Epirixanthes experienced relaxed or intensified selection compared with autotrophic relatives. KEY RESULTS: Plastomes of two species of Epirixanthes have become substantially degraded compared with that of autotrophic Polygala. Although the lack of photosynthesis is presumably homologous in the genus, the surveyed Epirixanthes species have marked differences in terms of plastome size, structural rearrangements, gene content and substitution rates. Remarkably, both apparently replaced a canonical plastid inverted repeat with large directly repeated sequences. The mitogenome of E. elongata incorporated a considerable number of fossilized plastid genes, by intracellular transfer from an ancestor with a less degraded plastome. Both plastid and mitochondrial genes in E. elongata have increased substitution rates, but the plastid genes of E. pallida do not. Despite this, both species have similar selection patterns operating on plastid housekeeping genes. CONCLUSIONS: Plastome evolution largely fits with patterns of gene degradation seen in other heterotrophic plants, but includes highly unusual directly duplicated regions. The causes of rate elevation in the sequenced Epirixanthes mitogenome and of rate differences in plastomes of related mycoheterotrophic species are not currently understood.

Peroxisome proliferator-activated receptor gamma expression in urothelial carcinomas of the bladder: association with differentiation, proliferation and clinical outcome.

AIMS: Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-activated transcriptional factor that regulates the transcription of various target genes. Our purpose is to investigate the clinicopathologic and prognostic significance of PPARgamma expression in human urothelial bladder cancer (BUC). METHODS: Immunohistochemistry was applied in 117 paraffin-embedded specimens of human BUC to detect the proteins PPARgamma and Ki67. The image analysis method was used for the evaluation of the immunohistochemical staining. RESULTS: PPARgamma protein was localized in the nuclei of the malignant cells. Its expression was inversely associated with the stage of BUCs (p<0.001), tumor grade (p=0.007) and the expression of the proliferation marker Ki67 (p=0.015) while it was found to exert a favorable effect on patients' overall survival (p=0.001). CONCLUSION: The findings of the present study suggest that in BUC, PPARgamma expression can identify patients with a better prognosis who suffer from more differentiated, non-invasive tumors, of a low proliferative potential.

Prognostic value of microsatellite instability determined by immunohistochemical staining of hMSH2 and hMSH6 in urothelial carcinoma of the bladder.

Mismatch repair (MMR) genes are involved in the recognition and repair of acquired DNA damage, which arises during cell division, thus playing an essential role in preserving genetic stability. Immunohistochemistry was applied to 130 specimens from urothelial carcinoma (UC) of the bladder to detect expression of MMR gene products hMSH2 and hMSH6, and to investigate its clinicopathological and prognostic value. hMSH2 and hMSH6 protein expression was exclusively detected in the nuclei of malignant cells. Of the 112 cases evaluable for hMSH2, 29 (25.9%) were negative and of the 130 UCs evaluable for hMSH6, 64 (49.2%) were negative, and were thus considered to depict MSI. Nuclear hMSH2 values were statistically lower in non-invasive UCs (Ta-T1) (p=0.013) and in carcinomas with decreased p53 staining (p=0.04). Lower hMSH6 values were more often met in well-differentiated tumors (p<0.0001) and in tumors with low expression of p53 (p=0.016), topoIIalpha and caspase 3 (p=0.017 and p=0.018, respectively). Both hMSH2- and hMSH6-negative immunoreactions were found to have a favorable impact on overall patient survival (p=0.041 and p=0.034, respectively), this finding being further verified in the multivariate analysis of hMSH2 (p=0.026). This is the first study to show that lack (and not reduction designated according to various cut-off points) of hMSH2 and hMSH6 correlated with non-invasive tumors of lower grade and is of favorable prognostic significance in patients suffering from bladder carcinoma.

Hydatid disease of the urinary tract: an update.

Hydatid disease constitutes an endemic zoonosis caused by different species of the cestode Echinococcus. The main organs affected are the liver and the lungs. Echinococcosis of the urinary tract is an extremely rare medical condition, met in 2-4% of cases. This pathologic entity has to be included in the differential diagnosis of occupying lesions of the urinary tract at any age, especially among patients in endemic areas. Meticulous laboratory and imaging control when taking into consideration the suspicion for the disease, can guarantee an accurate diagnosis and successful outcome.

Levobupivacaine intravesical injection for superficial bladder tumor resection--possible, effective, and durable. Preliminary clinical data.

BACKGROUND: General and spinal anesthesia are currently in widespread use during transurethral bladder tumor resection. However, local anesthetic methods are claimed to provide sufficient intra-operative analgesia and satisfactory post-operative pain management. We evaluated whether local levobupivacaine infiltration of the tumor would result in outcomes, in terms of intra-operative analgesia, similar to those for utilization of general anesthesia. Post-operative analgesia and patient satisfaction were also assessed. PATIENTS AND METHODS: Twenty patients with recurrent solitary bladder tumors were randomly allocated in two groups. Group A, underwent tumor resection under general anesthesia and group B was treated with resection after local levobupivacaine infiltration. Post-operative analgesia was evaluated with utilization of a visual analogue scale, ranging from 0 to 10, with higher scores indicating more intense pain perception. RESULTS: Group A patients demonstrated significantly lower visual analogue scale scores at t=0, which peaked at 4 h post-operatively. Group B scores were higher at t=0, declined over a 2 h interval and reached zero after t=4 h. Patients younger than 60 years and women benefitted more. Local anaesthesia was the method of pain control preferred by 90% of patients. CONCLUSION: Local levobupivacaine infiltration for transurethral bladder tumor resection seems feasible, providing intra and post-operative pain control. In this preliminary setting, general anesthesia provided a higher level of pain control in the immediate post-operative period (<4 h) while local levobupivacaine infiltration demonstrated excellent late post-operative analgesia (>4 h). Also, patients seem to prefer local to general anesthesia in future surgery.

Comparison of prolonged warm and cold ischemia on the solitary kidney during partial nephrectomy in a rabbit model.

The aim of this study was to investigate the patterns of renal function recovery during partial nephrectomy (PN) on an experimental solitary kidney rabbit model and establish the upper tolerable time limits of applied ischemia. Forty-eight New Zealand rabbits underwent an open right nephrectomy and after 30 days, the animals were clustered into five groups (A, B, C, D, E). The first four groups received an open left PN, under different types of ischemia. Groups A (n = 8) and B (n = 10) were subjected to 90 and 60 min of warm ischemia (WI), respectively, while groups C (n = 10) and D (n = 10) received 90 and 120 min of cold ischemia (CI) with ice-slush cooling. Group E (n = 10) served as sham group. Serum determinations of creatinine (SCr) and BUN were recorded preoperatively and on postoperative days (POD) 1, 3, 6 and 15. The animals were euthanized and the remaining kidneys were harvested and evaluated microscopically. The type and duration of ischemia were statistically significant parameters (P < 0.001). Groups B, C and D exhibited a similar pattern of recovery from trial initiation to the 15th POD (P = 0.788 and P = 0.068, respectively). Group A was extremely differentiated, with 100% mortality caused by uremia. The microscopic findings were consistent to the serum biochemistry. In our solitary kidney rabbit model, the upper limits of tolerable WI seem to be set on 60 min. CI can safely preserve the model's renal function--even up to 120 min.

Reduced insulin secretion in normoglycaemic patients with beta-thalassaemia major.

AIMS: To assess insulin sensitivity and secretion in the fasting state in regularly transfused patients with beta-thalassaemia major with normal glucose response during an oral glucose tolerance test and to estimate its possible relation to iron overload. METHODS: We measured fasting glucose, insulin and C-peptide levels in 24 patients with beta-thalassaemia major and 18 control subjects matched for age and body mass index. Insulin sensitivity and insulin release index were calculated according to the homeostasis model assessment (HOMA). Correlations with age, body mass index and serum ferritin were also calculated. RESULTS: Fasting glucose levels in patients were increased compared with control subjects (5.5 +/- 0.12 vs. 4.7 +/- 0.13 mmol/l, mean +/- SEM, P < 0.001). Pancreatic B-cell insulin secretion in the fasting state (estimated by SC(HOMA)) was lower in thalassaemic patients (SC(HOMA) 88.5 +/- 11.11 vs. 184.3 +/- 23.72 in control subjects, P < 0.001). Patients were then divided into those with impaired (IFG) and normal (NFG) fasting glucose. SC(HOMA) was higher in the patients with NFG compared with those with IFG patients (110.6 +/- 17.63 vs. 66.3 +/- 10.88, respectively, P < 0.05) but estimated insulin sensitivity (ISI(HOMA)) was similar. Plasma values of C-peptide correlated positively with ferritin (r = 0.42, P = 0.04) and SC(HOMA) (r = 0.45, P = 0.02) and negatively with ISI(HOMA) (r = -0.43, P = 0.03). CONCLUSIONS: These results support the concept that impaired B-cell function, as reflected by a reduction in the insulin secretion index, is present in beta-thalassaemic patients with normoglycaemia before changes in oral glucose tolerance tests are apparent.

Solitary hydatid cyst in the pelvis: a case report.

Hydatid disease mainly affects the liver and the lungs. Pelvic involvement have been rarely reported in the literature. Herein we present a rare case of isolated hydatid cyst of pelvis attached to the urinary bladder.

Hydatid disease of the seminal vesicle: a rare presentation of hydatid cyst.

Seminal vesicle belongs to the unusual sites of the hydatid cyst presentation. Even though the patient had a history of surgically treated hydatid disease of the liver, however, solitary echinococcal cyst of the seminal vesicle is a rare condition. Surgical removal of the cyst intact is the treatment of choice.

Cyclooxygenase-2 protein expression in relation to apoptotic potential and its prognostic significance in bladder urothelial carcinoma.

BACKGROUND: Cyclooxygenase-2 (COX-2), a critical enzyme in the conversion of arachidonic acid to prostaglandin E2, influences the biological behavior of human tumors, being involved in carcinogenesis, tumor progression, reduced apoptosis and differentiation. The aim of the present study was to investigate the role of COX-2 protein expression in urothelial carcinoma (UC) of the urinary bladder in relation to clinicopathological data and indices of apoptotic potential. MATERIALS AND METHODS: Immunohistochemistry was applied to 134 paraffin-embedded specimens of UC for the detection of COX-2, p53, bcl-2, caspase-3, bax protein, MLH1 and hTERT. RESULTS: Ninety-four UCs (70.1%) had an enhanced expression of COX-2. The COX-2 semi-quantitative expression was unrelated to tumor grade and local invasion, but it was positively linked with caspase-3 (CPP32) and bax protein semi-quantitative immunoreactivity (p = 0.007 and p = 0.026), as well as with the quantitative expression of MLH1 (p = 0.019). COX-2 was also found to be inversely correlated with the nuclear localization of the catalyst component of the telomerase complex, hTERT (p = 0.009). Multivariate statistical analysis showed that COX-2 immunopositivity was independently associated with worse prognosis of patients with non muscle-invasive UCs (p = 0.002). CONCLUSION: COX-2 overexpression, being possibly a subsequence of apoptosis activation, is associated with an unfavorable overall survival of patients with pTa-T1 UCs.

Accuracy of cystoscopy in predicting histologic features of bladder lesions.

PURPOSE: To correlate individual endoscopist impressions of the nature (benign/malignant) of a urothelial lesion and, in the case of malignancy, "clinical" grade and stage of bladder lesions with the histologic findings after transurethral biopsy/resection. Furthermore, we compared the assessments of trainees and experienced urologists. PATIENTS AND METHODS: We considered 146 patients submitted to cystoscopy and transurethral excision of tumors or biopsy of suspect regions. Clinical and pathologic diagnoses were compared, and the agreement between reports was assessed by calculating kappa statistics. RESULTS: Complete agreement between the cystoscopic and histologic diagnoses was found in 131 of 146 cases. Both specialists and trainees had a tendency to overdiagnose bladder cancer, and they were not effective in predicting the precise stage: complete agreement with the pathologic stage was observed in 66.1% and 64.5% of cases, respectively. Grade was assessed correctly in 55.1% and 54.3% of the cases. The two teams of surgeons expressed complete agreement in the prediction of stage in 78.7% of cases (kappa 0.658) and of grade in 73.2% of cases (kappa 0.584). CONCLUSIONS: Our study confirms the diagnostic value of cystoscopy, given the high recognizability of the malignant nature of a lesion by both specialists and trainees. However, cystoscopy is less satisfactory for the characterization of the stage and grade of a cancer. The comparative assessment of the endoscopic and pathologic findings could prove useful to assess the effectiveness of training in endoscopy.

Docetaxel and cisplatin with granulocyte colony-stimulating factor (G-CSF) versus MVAC with G-CSF in advanced urothelial carcinoma: a multicenter, randomized, phase III study from the Hellenic Cooperative Oncology Group.

PURPOSE: The combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) represents the standard regimen for inoperable or metastatic urothelial cancer, but its toxicity is significant. We previously reported a 52% response rate (RR) using a docetaxel and cisplatin (DC) combination. The toxicity of this regimen compared favorably with that reported for MVAC. We thus designed a randomized phase III trial to compare DC with MVAC. PATIENTS AND METHODS: Patients with inoperable or metastatic urothelial carcinoma; adequate bone marrow, renal, liver, and cardiac function; and Eastern Cooperative Oncology Group performance status < or = 2 were randomly assigned to receive MVAC at standard doses or docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) every 3 weeks. All patients received prophylactic granulocyte colony-stimulating factor (G-CSF) support. RESULT: Two hundred twenty patients were randomly assigned (MVAC, 109 patients; DC, 111 patients). Treatment with MVAC resulted in superior RR (54.2% v 37.4%; P =.017), median time to progression (TTP; 9.4 v 6.1 months; P =.003) and median survival (14.2 v 9.3 months; P =.026). After adjusting for prognostic factors, difference in TTP remained significant (hazard ratio [HR], 1.61; P =.005), whereas survival difference was nonsignificant at the 5% level (HR, 1.31; P =.089). MVAC caused more frequent grade 3 or 4 neutropenia (35.4% v 19.2%; P =.006), thrombocytopenia (5.7% v 0.9%; P =.046), and neutropenic sepsis (11.6% v 3.8%; P =.001). Toxicity of MVAC was considerably lower than that previously reported for MVAC administered without G-CSF. CONCLUSION: MVAC is more effective than DC in advanced urothelial cancer. G-CSF-supported MVAC is well tolerated and could be used instead of classic MVAC as first-line treatment in advanced urothelial carcinoma.

Non-endothelial KDR/flk-1 expression is associated with increased survival of patients with urothelial bladder carcinomas.

AIMS: To investigate the immunohistochemical expression of KDR/flk-1 in a series of 114 urothelial bladder carcinomas in relation to clinicopathological parameters, Ki67, p53 and Bcl-2 protein expression and patient survival. KDR/flk-1 is a high-affinity tyrosine kinase receptor for vascular endothelial growth factor (VEGF), on vascular endothelium. However, there is increasing evidence that KDR/flk-1 is also expressed by normal non-endothelial and tumour cells. METHODS AND RESULTS: Immunohistochemistry was performed on paraffin sections using monoclonal and polyclonal antibodies. Statistical analysis was univariate (chi2 log rank test) and multivariate (Cox's model). KDR/flk-1 expression was observed in the cytoplasm of cancerous cells in 68.4% of cases. No statistically significant associations were observed between KDR/flk-1 expression and grade or stage of urothelial carcinomas, Ki67, p53 or Bcl-2 expression. In contrast, widespread KDR/flk-1 expression in more than 50% of cancerous cells was associated with increased survival, on univariate and multivariate analysis (P = 0.0119 and P = 0.042, respectively). CONCLUSIONS: Although the biological significance of non-endothelial KDR/flk-1 expression has not yet been elucidated, its association with better patient survival may be related to the failure of non-endothelial KDR/flk-1 to mediate angiogenic and mitogenic effects.

MMP-3 mRNA and MMP-3 and MMP-1 proteins in bladder cancer: a comparison with clinicopathologic features and survival.

Matrix metalloproteinases (MMPs) are proteolytic enzymes important at several points during multistep neoplastic progression. Although MMP-1 and MMP-3 have been implicated in the progression of various human cancers, their expression in bladder cancer has not been addressed. Immunohistochemistry (Strept-ABC-HRP method) and in situ hybridization were performed to detect MMP-1 protein, MMP-3 protein, and MMP-3 mRNA, respectively, in 59 transitional cell bladder carcinomas. To assess the role of these MMPs in bladder cancer, their expression was evaluated in relation to known clinicopathologic parameters and patients' disease-free and overall survival. Immunoreactivity for MMP-1 and MMP-3 proteins was observed in the cytoplasm of cancer cells in 30.5% and 24% of samples, respectively. Transcripts for MMP-3 mRNA were localized in stromal cells in 71.2% of cases and in cancer cells in 49% of cases. MMP-1 immunoreactivity demonstrated a statistically significant association with deeply invasive and grade III tumors versus superficial and lower grade tumors. MMP-3 protein immunoreactivity and MMP-3 mRNA immunolocalization did not associate with the parameters studied. However, MMP-3 mRNA localization in stromal cells demonstrated a borderline association with poor patients' disease-free and overall survival. In conclusion, the authors' results demonstrate a differential expression between MMP-1 and MMP-3 in bladder cancer; MMP-1 appears to participate in invasiveness and possibly in loss of differentiation in urothelial carcinomas in contrast to MMP-3.

Predictive value of topoisomerase II alpha immunostaining in urothelial bladder carcinoma.

AIMS: The nuclear enzyme DNA topoisomerase II has been shown to be required for chromatin condensation and chromosomal segregation during mitosis; its isoform topo II alpha is linked with active cell proliferation in mammalian cells. The aim of this study was to examine the relation of the expression of topo II alpha to the biological behaviour of conventional urinary bladder cancer. METHODS: Formalin fixed, paraffin wax embedded tissue from 94 specimens of bladder urothelial cancer were immuno-histochemically stained for topo II alpha. For each case, a topo II alpha index was determined. A similar index had been determined for Ki-67, a known cell proliferation marker. Each case had also been graded, staged, and evaluated for DNA ploidy as well as for p53 and bcl-2 immunoreactivity. RESULTS: Raised topo II alpha expression (in > or = 10% of malignant nuclei) correlated with two adverse prognosticators--high grade (p = 0.027) and invasion of the muscularis propria (p = 0.013), but with no other evaluated parameter. By multivariate survival analysis using Cox's proportional hazard model, high expression of topo II alpha was found to be predictive for worse survival (p = 0.0047). Patients' age, tumour stage, and grade were also retained as independent prognostic factors (p = 0.0349, p = 0.00005, and p = 0.0130, respectively). The negative influence of increased topo II alpha immunopositivity on patients' survival was also seen in the subgroup of patients with non-muscle invasive carcinomas (p = 0.0004), in patients with a bcl-2 negative phenotype (p = 0.0330), and in those with low Ki-67 indices (p = 0.0341). CONCLUSIONS: Because topo II alpha and Ki-67 failed to demonstrate a significant interrelation, they appear to be different molecules that both function at separate phases in the complex process of cellular proliferation. The assessment of increased topo II alpha immunoreactivity in specimens from urothelial carcinomas might help to select patients (particularly among those with superficial tumours) in the worse prognostic categories for new therapeutic strategies.

Extravesical foreign body presenting as a bladder tumor.

Although foreign bodies left in the abdominal cavity may remain asymptomatic for long periods, they may also cause serious complications. We present a case of gauze forgotten in the lower abdomen which remained asymptomatic for almost 1 year. When a granuloma had formed, it infiltrated the bladder wall giving the clinical and imaging appearance of an invasive bladder tumor.

Oxidative stress of red blood cells during Bacillus Calmette-Guerin intravesical instillations.

Although Bacillus Calmette-Guerin (BCG) intravesical instillation is widely accepted as a very effective modality in treating bladder carcinoma in situ, and in preventing superficial bladder cancer recurrence, its mechanism of action is not yet fully understood. The antitumor effects of BCG are mostly related to local immunological events but a systemic activation of the immune system cannot be excluded. The objective of the present study was to estimate the systemic production of oxidants during intravesical BCG treatment. Systemic production of oxidants was estimated by assessing the red blood cells (RBC) oxidative stress in twelve patients undergoing BCG immunotherapy for bladder carcinoma in situ. RBC oxidative stress induced by peroxynitrite was determined by luminol-enhanced chemiluminescence. During the treatment period, the RBC oxidative stress revealed a biphasic curve of changes: after an initial 5-fold increase, it dropped to pretreatment levels following the 4th instillation. Intravesical BCG administration induced systemic production of oxygen free radicals that may reflect a systemic activation of the immune system.

Prognostic value of E-cadherin, beta-catenin, P120ctn in patients with transitional cell bladder cancer.

BACKGROUND: Loss of E-cadherin-catenin mediated adhesion is known to play a major role in tumour progression in many human carcinomas. MATERIALS AND METHODS: By means of immunohistochemistry, we have investigated the expression of E-cadherin, beta-catenin and p120ctn in 102 transitional cell bladder carcinomas (TCCs) and statistically analysed these expressions with known clinicopathological parameters and patient survival. RESULTS: Abnormal expression of E-cadherin, beta-catenin and p120ctn was associated with high grade and high stage of TCCs (p < 0.001). Abnormal beta-catenin expression demonstrated a statistically significant correlation with poor patient survival (p = 0.03) while abnormal E-cadherin expression was associated with poor survival in patients with muscle invasive TCCs (p = 0.025). However, in multivariate statistical analysis a suggestive association with poor survival was observed only for E-cadherin (p = 0.06). Simultaneous abnormal expression of all the molecules demonstrated an association of suggestive significance with poor patient survival (p = 0.07). CONCLUSION: E-cadherin expression may be a useful prognostic marker in patients with invasive TCCs.

Docetaxel and cisplatin combination chemotherapy in advanced carcinoma of the urothelium: a multicenter phase II study of the Hellenic Cooperative Oncology Group.

PURPOSE: Both docetaxel and cisplatin have moderate activity in patients with advanced urothelial cancer. We performed a multicenter phase II study in order to assess the efficacy and toxicity of the combination of these two agents in patients with advanced carcinoma of the urothelium. PATIENTS AND METHODS: Sixty-six patients not amenable to curative surgery or irradiation were enrolled onto this cooperative group study and treated on an outpatient basis with docetaxel 75 mg/m2 followed by cisplatin 75 mg/m2, both administered intravenously. Granulocyte-colony stimulating factor was administered subcutaneously at a dose of 5 micrograms/kg daily from day 5 until resolution of neutropenia. The chemotherapy was administered every three weeks for a maximum of six courses in patients without evidence of progressive disease. RESULTS: Thirty-four of sixty-six patients (52%, 95% confidence interval 40%-64%) demonstrated objective responses, with eight achieving clinical complete responses and twenty-six partial responses. A multivariate logistic regression analysis indicated that the patients most likely to respond were those without lung metastasis and without weight loss before treatment. The median duration of response was 6.1 months and the median times to progression and survival for all patients were 5 and 8 months, respectively. Absence of anemia, of liver metastases and of weight loss correlated with longer survival. Grade > or = 3 toxicities included granulocytopenia in 33% of patients, anemia in 14%, diarrhea in 13% and emesis in 7% of patients. CONCLUSION: The combination of docetaxel and cisplatin appeared relatively well tolerated and moderately active in patients with advanced urothelial cancer. The patients most likely to benefit were those without weight loss and without lung or liver metastases.