pirarubicin and Kidney-Neoplasms

The circadian timing of surgery, anticancer drugs, radiation therapy, and biologic agents can result in improved toxicity profiles, tumor control, and host survival. Optimally timed cancer chemotherapy with doxorubicin or pirarubicin (06:00h) and cisplatin (18:00h) enhanced the control of advanced ovarian cancer while minimizing side effects, and increased the response rate in metastatic endometrial cancer. Therapy of metastatic bladder cancer with doxorubicin-cisplatin was made more tolerable by this same circadian approach resulting in a 57% objective response rate. This optimally timed therapy is also effective in the adjuvant setting, decreasing the expected frequency of metastasis from locally advanced bladder cancer. Circadian fluorodeoxyuridine (FUDR) continuous infusion (70% of the daily dose given between 15:00h and 21:00h) has been shown effective for metastatic renal cell carcinoma resulting in 29% objective response and stable disease of more than 1 yr duration in the majority of patients. Toxicity is reduced markedly when FUDR infusion is modulated to circadian rhythms. In a multicenter trial in patients with metastatic renal cell cancer, patients were randomized to a flat or a circadian-modified FUDR infusion. This study confirmed a significant difference in toxicity and dose intensity, favoring the circadian-modified group. Hormone refractory metastatic prostate cancer has been treated with circadian-timed FUDR chemotherapy; however, without objective response. Biological agents such as interferon-alpha and IL-2 have shown low but effective disease control in metastatic renal cell cancer, however, with much toxicity. Each of these cytokines shows circadian stage dependent toxicity and efficacy in model systems. In summary, the timing of anthracycline, platinum, and fluoropyrimidine-based drug therapies during the 24h is relevant to the toxic therapeutic ratio of these agents in the treatment of gynecologic and genitourinary cancers.

Topics: Animals; Antineoplastic Agents; Carcinoma, Renal Cell; Cell Cycle; Chronotherapy; Circadian Rhythm; Cisplatin; Doxorubicin; Endometrial Neoplasms; Female; Floxuridine; Genital Neoplasms, Female; Humans; Kidney Neoplasms; Male; Ovarian Neoplasms; Prostatic Neoplasms; Rats; Urinary Bladder Neoplasms; Urogenital Neoplasms

Autologous bone marrow transplantation (ABMT) and peripheral blood stem cell transplantation (PBSCT) are increasingly used to support high-dose chemotherapy for solid tumors of childhood. In this review we described practical aspects of myeloablative chemotherapy rescued by ABMT, PBSCT or combination of ABMT and PBSCT for the treatment of children with high-risk solid tumor, involving our experiences in 15 cases. Indication, method of harvesting bone marrow and peripheral blood stem cells, cryopreservation, transplantation, selection of anti-neoplastic agents for preconditioning, nutritional and G-CSF support, engraftment and outcomes for prognosis were discussed. In comparing the engraftment of stem cells between ABMT and PBSCT, the acceleration of platelet and erythrocyte recovery is less impressive, although there is a tendency to more rapid recovery of granulocyte in PBSCT group. The outcomes are distinctly improved only in patients who showed complete remission after induction chemotherapy, radiation and surgical excision. A better prognosis will be conferred especially in neuroblastoma and entities of small round cell tumor. It is noteworthy that relapses can occur as distant metastasis considerable years after complete clinical remission. This may be largely contributed by contaminated malignant cells in both harvested bone marrow and peripheral blood stem cells. There is no significant difference between the relapse rates after ABMT and PBSCT.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Purging; Bone Marrow Transplantation; Carboplatin; Child; Combined Modality Therapy; Cryopreservation; Doxorubicin; Etoposide; Hematopoietic Stem Cell Transplantation; Humans; Kidney Neoplasms; Neoplasms; Neuroblastoma; Rhabdomyosarcoma; Wilms Tumor

Eighty patients with measurable metastatic colon or renal cancer, melanoma, or sarcoma entered these Phase II studies. A dose of 25 mg/m2/day of Pirarubicin (THP) for 3 consecutive days every 4 weeks for the first patients, and then 20 mg/m2/day for 3 days every 3 weeks was given by i.v. push. These patients received 225 cycles for a median cumulative dose of 165 mg/m2 (range: 55-630). The mean number of cycles given was 2.8 (range: 1-8). Only 3 partial responses and 18 stable disease (22%) were observed. Hematologic toxicity was the main problem; it was responsible for one death and a 19% and 44% incidence of grade 3 and 4 WHO neutropenia, respectively. Alopecia was rare (4%). Chemotherapy was discontinued in three cases because of suspicion of cardiac toxicity, but only one patient had a significant drop in left ventricular ejection fraction at a cumulative THP dosage of 120 mg/m2. A lack of efficacy in renal and colon cancer and melanoma was presupposed and confirmed by these trials. Due to pretreatment with anthracycline in most patients, definite evaluation of THP in soft tissue sarcoma could not be given.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Carcinoma; Colonic Neoplasms; Doxorubicin; Drug Administration Schedule; Humans; Kidney Neoplasms; Melanoma; Middle Aged; Sarcoma; Soft Tissue Neoplasms

The role of surgery was evaluated in 19 stage III and 102 stage IV neuroblastoma patients, all of whom were treated with intensive induction chemotherapy by the Study Group of Japan between January 1985 and March 1990. For stage III neuroblastoma, surgical intervention at the primary site was performed in 18 of the 19 patients, 9 during and 9 after the first three cycles of A1 regimen, consisting of high-dose cyclophosphamide, vincristine, THP-adriamycin, and cis-platinum. Gross complete resection of primary tumor and regional lymph nodes was feasible in 17 of the 19 patients (89%), and the survival rate for the 17 patients were 79%, 70%, and 70% at 2 years, 3 years, and 4 years, respectively. For stage IV, surgical intervention at the primary site was performed in 92 of the 102 patients (90%): 30 cases during the first 3 cycles of A1 chemotherapy and 62 cases after that, with gross complete resection accomplished in 81 of the 102 patients (79%). The 81 patients with gross complete resection achieved had a better prognosis than those 11 patients with partial resection (P less than .05). Overall survival rate was 62% at 2 years for 27 patients who underwent complete resection after 3 cycles of A1 when resolution of all metastases was obtained, whereas the survival was 52% at 2 years for 31 patients who similarly underwent complete resection but when evidence of persistent metastases was present. Patients in whom the ipsilateral kidney was preserved at surgery had an outcome superior to that of those with associated nephrectomy (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cyclophosphamide; Doxorubicin; Humans; Infant; Japan; Kidney Neoplasms; Neoplasm Staging; Nephrectomy; Neuroblastoma; Preoperative Care; Vincristine

Clear cell sarcoma of the kidney (CCSK) is a rare and aggressive malignant renal tumor. We describe our experience with neoadjuvant transcatheter arterial chemoembolization (TACE) and systematic chemotherapy for the treatment of advanced CCSK in children.. Between January 2010 and December 2016, seven patients (3 boys and 4 girls; median 2.2 years) with advanced CCSK received preoperative TACE of renal artery and systemic chemotherapy. The chemoembolic emulsion for TACE consisted of cisplatin, pirarubicin, vindesine, and iodized oil. Preoperative systemic chemotherapy with vindesine, ifosfamide, and etoposide was administered three weeks after TACE. Nephrectomy was performed three weeks after systemic chemotherapy. After surgery, patients received radiotherapy and postoperative chemotherapy.. No cardiotoxicity, renal insufficiency, or hepatic dysfunction was found in any patients. Grade II-III marrow suppression developed in four patients. One patient with tumor progress during neoadjuvant therapy failed to successfully undergo surgery and died. Six patients underwent nephrectomy after neoadjuvant therapy. Median follow-up period was 49.5 months (range, 11-83 months). Five patients have recurrence-free survival. One patient is still in postoperative chemotherapy after nephrectomy, radiotherapy and thoracoscopic resection of lung metastases.. Neoadjuvant TACE and systemic chemotherapy appeared to be feasible in the treatment of advanced CCSK in this pilot study.. A case series with no comparison group.. Level IV.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemoembolization, Therapeutic; Child; Child, Preschool; Cisplatin; Combined Modality Therapy; Doxorubicin; Female; Humans; Infant; Iodized Oil; Kidney; Kidney Neoplasms; Male; Neoadjuvant Therapy; Nephrectomy; Pilot Projects; Retrospective Studies; Sarcoma, Clear Cell; Treatment Outcome; Vindesine

Enteropathy-associated T-cell lymphoma (EATL), an intestinal tumor of intraepithelial T lymphocytes, is a rare and highly aggressive disease. We herein describe a case of type II EATL with massive pyoid ascites in which a histological examination could not be performed despite emergency laparotomy that was successfully diagnosed using flow cytometry and the cell block technique to analyze the celomic fluid. This case suggests that EATL should be included in the differential diagnosis of pyoid ascites of unknown origin and that flow cytometry and the cell block technique of assessing celomic fluid are useful procedures for diagnosing EATL, especially in cases in which conducting a histological examination is impossible.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Ascites; Carcinoma, Renal Cell; Cyclophosphamide; Doxorubicin; Emergencies; Enteropathy-Associated T-Cell Lymphoma; Fatal Outcome; Female; Flow Cytometry; Humans; Intestinal Perforation; Kidney Neoplasms; Laparotomy; Multiple Organ Failure; Neoplasms, Second Primary; Nephrectomy; Omentum; Pleural Effusion; Prednisolone; Respiration, Artificial; Respiratory Insufficiency; Vincristine

Lexatumumab, a human agonistic monoclonal antibody against tumor necrosis factor (TNF)-related apoptosis-inducing ligand receptor-2 (TRAIL-R2), is a promising molecular-targeted therapeutic agent. Our past study indicated that low concentrations of doxorubicin sensitized renal cell carcinoma (RCC) cells to lexatumumab-mediated apoptosis. The present study was designed to examine the cellular and molecular effects of lexatumumab and anthracyclines in RCC cells. The treatment of human RCC cells with lexatumumab in combination with anthracyclines, epirubicin, and pirarubicin had a synergistic cytotoxicity. A marked synergistic apoptosis was induced by lexatumumab in combination with epirubicin or pirarubicin. Epirubicin and pirarubicin significantly increased the TRAIL-R2 expression at both the mRNA and the protein levels. The combination-induced cytotoxicity was significantly suppressed by the human recombinant DR5:Fc chimeric protein. To further explore the molecular mechanisms in this synergistic cytotoxicity with lexatumumab and anthracyclines, the changes in 84 apoptosis-related genes were evaluated by a quantitative polymerase chain reaction (PCR) array. Among these genes, 18 (CD40LG, FASLG, LTA, TNSF7, FAS, BAG3, BAK1, BAX, BID, BIK, BCL10, caspase-1, caspase-5, caspase-6, caspase-10, TNF receptor-associated factor 1, PYCARD, and CIDEA) were significantly upregulated and eight (TNF receptor-associated factor 4, TNFRSF11B, TNF, BCL2, BCL2L1, BNIP3L, caspase-9, and DAPK1) were downregulated at mRNA levels in RCC cells cotreated with lexatumumab and epirubicin. Furthermore, the upregulation of mRNA levels of PYCARD and CIDEA was confirmed using real-time reverse transcriptase-PCR analysis. The present study demonstrates that anthracylines sensitize RCC cells to lexatumumab-mediated apoptosis by inducing TRAIL-R2 expression, and the utility of PCR array to elucidate the mechanism of synergistic apoptosis.

Topics: Anthracyclines; Antibodies, Monoclonal; Antineoplastic Agents; Apoptosis; Carcinoma, Renal Cell; Caspases; Cell Line, Tumor; Doxorubicin; Drug Synergism; Epirubicin; Humans; Kidney Neoplasms; Polymerase Chain Reaction; Receptors, TNF-Related Apoptosis-Inducing Ligand

To evaluate the therapeutic effect of preoperative transcatheter arterial chemoembolization (TACE) combined with short-term systematic chemotherapy in the treatment of advanced Wilms tumor.. This was a retrospective study on 66 patients with unilateral advanced Wilms tumor, age 5 months to 11 years (median, 2.9 years; 30 boys and 36 girls), treated at our institution between 1995 and 2007. Characteristics of the patient population were maximal tumor diameter > 10 cm, or involvement of periaortic lymph nodes, or inferior vena cava invasion, or distal metastasis, or tumor with anaplastic histology. Patients were divided into three groups. Twenty patients were treated with conventional preoperative chemotherapy (PC group) using vindesine, actinomycin D, and pirarubicin for 4 weeks; 21 patients were treated in the TACE group with preoperative renal arterial chemoembolization using Lipiodol-pirarubicin-vindesine emulsion; and 25 patients were treated with preoperative chemoembolization combined with short-term systematic chemotherapy (T+S) for 2 weeks.. No drug-induced cardiotoxicity, nephrotoxicity, or hepatic dysfunction was observed. Complete surgical removal of the tumor was achieved in 12 (65.0%), 17 (80.9%), and 22 (88.0%) patients in the PC, TACE, and T+S groups, respectively (T+S group vs PC group, P = .030). The 2-year relapse-free survival rates were 65.0%, 80.9%, and 100.0% in the PC, TACE, and T+S groups, respectively (T+S vs PC, P = .001).. From our experience, preoperative chemoembolization combined with short-term systematic chemotherapy is able to achieve higher rates of complete tumor resection and relapse-free survival in the treatment of advanced Wilms tumor.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemoembolization, Therapeutic; Chemotherapy, Adjuvant; Child; Child, Preschool; China; Dactinomycin; Disease-Free Survival; Doxorubicin; Ethiodized Oil; Female; Humans; Infant; Kaplan-Meier Estimate; Kidney Neoplasms; Male; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm Staging; Nephrectomy; Retrospective Studies; Survival Rate; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; Vindesine; Wilms Tumor

Anti-Fas monoclonal antibody (mAb) kills Fas-expressing cells by apoptosis. Several anticancer agents also mediate apoptosis and may share common intracellular pathways leading to apoptosis with Fas. Thus, we reasoned that combination treatment of drug-resistant cells with anti-Fas mAb and drugs might overcome their resistance. We investigated whether anticancer agents enhance Fas-mediated apoptosis and cytotoxicity against renal cell carcinoma (RCC) cells. Treatment of ACHN RCC cells with anti-Fas mAb in combination with 5-fluorouracil, vinblastine, IFN-alpha, or IFN-gamma did not overcome resistance to these agents. However, combination treatment with anti-Fas mAb and Adriamycin (ADR) resulted in a synergistic cytotoxic effect. Furthermore, synergy was also obtained even when the exposure time was shortened from 24 h to 8 or 2 h. Synergy was also achieved in four other RCC cell lines and five freshly derived human RCC cells. Treatment with anti-Fas mAb in combination with epirubicin or pirarubicin also resulted in a synergistic cytotoxic effect on ACHN cells. Similar results were achieved with a combination of humanized anti-Fas mAb and ADR. Incubation of ACHN cells with ADR augmented the expression of Fas and p53, but not Bcl-2, Bax, or caspase-3. However, the activity of caspase-3 itself was apparently enhanced after treatment with ADR alone or combined treatment with anti-Fas mAb. The synergy obtained in cytotoxicity with anti-Fas mAb and ADR was also achieved in apoptosis. Exposure of ACHN cells and freshly derived RCC cells to ADR enhanced their susceptibility to lysis by peripheral blood lymphocytes and tumor-infiltrating lymphocytes. This study demonstrates that combination treatment of RCC cells with anti-Fas mAb and ADR might overcome their resistance. The sensitization required a low concentration of ADR and a short exposure time, thus supporting the potential in vivo application of a combination of ADR and anti-Fas mAb or immunotherapy in the treatment of ADR- and/or immunotherapy-resistant RCC.

Topics: Acridine Orange; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; bcl-2-Associated X Protein; Carcinoma, Renal Cell; Caspase 3; Caspases; Dose-Response Relationship, Drug; Doxorubicin; Drug Interactions; Epirubicin; fas Receptor; Fluorescent Dyes; Fluorouracil; Humans; Immunohistochemistry; Interferon-alpha; Interferon-gamma; Kidney Neoplasms; Lymphocytes, Tumor-Infiltrating; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Time Factors; Tumor Cells, Cultured; Tumor Suppressor Protein p53; Vinblastine

The patient was a 71-year-old man who had been diagnosed as having a left renal pelvic cancer with liver metastasis. We performed total left nephroureterectomy with lymphnode cleaning and partial resection of the liver. Because abdominal CT 5 months after the operation revealed multiple metastasis of the liver, we performed chemotherapy with a regimen consisting of methotrexate 50 mg (intravenous injection), cisplatin 30 mg and pirarubicin 20 mg (intraarterial infusion), and leucovorin 3 mg (intramuscular injection), three times at intervals of 6 hours. Ten days after chemotherapy, CT revealed the disappearance of most of the liver metastatic lesions, and a partial response was obtained. We are now performing the regimen at an interval of a month to a month and one-half to control the metastatic lesions.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Transitional Cell; Cisplatin; Doxorubicin; Hepatic Artery; Humans; Infusions, Intra-Arterial; Infusions, Intravenous; Injections, Intramuscular; Kidney Neoplasms; Kidney Pelvis; Leucovorin; Liver Neoplasms; Lymph Node Excision; Lymphatic Metastasis; Male; Methotrexate

We evaluated the usefulness of in vitro tumor culture system using a specialized collagen gel matrix (CGM assay) as a chemosensitivity test.. Chemosensitivity results of CGM assay were compared with other in vivo and in vitro assays on an implantable murine bladder tumor cell line (MBT-2). In addition we investigated the possibility of the clinical use of CGM assay using clinical specimens obtained from urogenital malignant tumor patients by comparing the result with that of the other chemosensitivity test, SDI testing using single cells (conventional SDI test). Methods of CGM assay were as follows. Tumor tissues on the collagen gel matrices were incubated under the existence of anticancer drugs following 4 days preculture. Drug sensitivities were evaluated by counting the number of viable cells adjusted to the tumor weight.. Inhibition rates in MBT-2 were high in the order of mitomycin C, cisdiamminedichloroplatinum (II), (2"R)-4'-0-tetrahydropyranyl adriamycin. Four of 6 anticancer drugs were decided as chemosensitive drugs. These results corresponded to the results of the antitumor effects on subcutaneously transplanted MBT-2 in vivo, moreover was correlated well with those of the conventional SDI test. Twenty of 22 cases, including 11 of 13 bladder cancer cases, 1 of 3 renal cancer cases, 2 of 3 testicular cancer cases and 1 of 1 adrenal cortical cancer cases, were evaluable in the clinical study of the CGM assay. Corresponding rates between the results of the CGM assay and those of the conventional SDI test performed simultaneously in 12 cases were excellent for each anticancer drug.. This CGM assay can serve as an effective tool for chemosensitivity testing because of its convenience and high evaluable rate.

Topics: Animals; Antineoplastic Agents; Bleomycin; Carcinoma, Renal Cell; Cisplatin; Collagen; Culture Media; Doxorubicin; Drug Screening Assays, Antitumor; Etoposide; Female; Humans; Kidney Neoplasms; Mice; Mice, Inbred C3H; Mitomycin; Urinary Bladder Neoplasms; Vinblastine

We report a case of left renal cell carcinoma extending into vena cava with malignant peritoneal mesothelioma. A 41-year-old man presented to our outpatient clinic with macroscopic hematuria. Upon laparotomy, numerous white nodules were identified on diaphragm and serosa of liver, stomach, small intestine and mesentery. Biopsied specimen showed malignant mesothelioma of peritoneum and renal cell carcinoma of left kidney. He was treated with intraperitoneal cisplatinum and intravenous pirarubicin for mesothelioma, and chemoembolization for renal tumor. After two courses of therapy, he suffered from disseminated intravascular coagulation and died of subarachnoid hemorrhage. Autopsy revealed that intraperitoneal nodules were markedly decreased in number and renal tumor had changed into hemorrhagic necrosis, but tumor thrombus in vena cava had little necrotic change.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Renal Cell; Cisplatin; Doxorubicin; Embolization, Therapeutic; Humans; Kidney Neoplasms; Male; Mesothelioma; Neoplasms, Multiple Primary; Peritoneal Neoplasms

Twenty milligrams of (2"R)-4'-O-tetrahydropyranyladriamycin (THP) was administered intravenously to 14 patients with renal cell carcinoma and 11 with urinary bladder tumor at the start of surgery. Heparinized peripheral blood samples were collected at regular intervals and separated into plasma and blood cell fractions by centrifugation for the estimation of the THP concentration. The THP concentrations in the surgical specimens were also studied. In the tissue of renal cell carcinoma, the nuclear fraction was obtained by fractionation in order to estimate the THP concentration. The THP concentrations of the plasma and blood cell fractions in both renal cell carcinoma and urinary bladder tumor gradually decreased with the lapse of time after administration. In renal cell carcinoma, grade 3 tumors revealed lower tissue and nuclear concentrations of THP than those of grade 1 and 2 tumors. Likewise, the tissue and nuclear concentrations of high-stage tumors were lower than those of low-stage tumors. On the other hand, in urinary bladder tumors, the THP concentrations in the tumors were found to be higher than those in normal urinary mucosa and muscle.

Topics: Carcinoma, Renal Cell; Combined Modality Therapy; Doxorubicin; Humans; Infusions, Intravenous; Kidney Neoplasms; Urinary Bladder Neoplasms

A Phase II clinical trial of a new anthracycline, (2''R)-4'-0-tetrahydropyranyladriamycin (THP), was performed in 137 patients with urological malignancies. Out of them, 111 patients were evaluated for tumor responses and 125 patients were evaluated for adverse effects. In cases of intravenous administration, overall response rate was 18.5% (22.2% for bladder cancer, 30.0% for tumors of the renal pelvis and ureter, and 6.7% for prostatic cancer). In the case of intra-arterial administration, overall response rate was 42.9% (50.0% for bladder cancer). For 50 patients with superficial bladder cancer intravesical chemotherapy with THP was performed. Sixteen patients showed complete disappearance of the tumor, 2 patients showed more than 90% tumor regression and 12 patients showed more than 50% tumor regression, respectively. Overall response rate was 60%. Cardiotoxicity was minimal. Alopecia was noted in a total of 16 patients, but this was minimal. Leukocytopenia was the major adverse effect among patients undergoing systemic THP administration. In conclusion, THP was most effective against transitional cell carcinoma of the urinary tract.

Topics: Adult; Aged; Alopecia; Anorexia; Carcinoma, Transitional Cell; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Female; Humans; Infusions, Parenteral; Kidney Neoplasms; Leukopenia; Male; Middle Aged; Urinary Bladder Neoplasms; Urologic Neoplasms

Each of 5 patients with renal cell carcinoma and urinary bladder tumor who were operated on at the department of urology, Hamamatsu University School of Medicine and its affiliated hospitals, received 20 mg of 4'-O-tetrahydropyranyladriamycin (THP) intravenously at the beginning of surgery. Heparinized peripheral blood samples were collected at regular intervals and separated in plasma and blood cell fractions by centrifugation for the estimation of THP. The THP concentration of the surgical specimen was also studied. In renal cell carcinoma, the surgical specimen was divided into cytoplasm and nuclear fractions, and the THP concentration in each fraction was measured. The THP concentration gradually decreased in the plasma and blood cell fractions with passage of time after the administration in both renal cell carcinoma and urinary bladder tumor. In renal cell carcinoma, although the tumor revealed a lower concentration of THP compared with the normal renal cortex and medulla, the nuclear fraction of the tumor showed a higher concentration than those of the normal renal cortex and medulla. In contrast to renal cell carcinoma, the THP concentration of the urinary bladder tumor was found to be higher than those of the normal urinary bladder mucosa and muscle.

Topics: Carcinoma, Renal Cell; Chromatography, High Pressure Liquid; Doxorubicin; Humans; Injections, Intravenous; Kidney Neoplasms; Tissue Distribution; Urinary Bladder Neoplasms