National Cancer Institute®
Last Modified: April 1, 2002
UI - 11900231
AU - Dimopoulou I; Galani H; Dafni U; Samakovii A; Roussos C; Dimopoulos MA
TI - A prospective study of pulmonary function in patients treated with paclitaxel and carboplatin.
SO - Cancer 2002 Jan 15;94(2):452-8
AD - Department of Pulmonary and Critical Care, Evangelismos Hospital, Medical School, Athens, Greece. firstname.lastname@example.org
BACKGROUND: Adverse effects of paclitaxel and carboplatin have been well described; however, pulmonary toxicity after patients receive this regimen has not been investigated extensively. METHODS: To clarify this issue, 33 consecutive patients who were treated with paclitaxel and carboplatin underwent prospective evaluation of respiratory function, which included pulmonary symptoms, pulmonary function tests (PFTs), arterial blood gas levels, and radiographic studies. Assessment was performed before and after completion of chemotherapy in all patients. Patients with substantial declines in PFTs, defined as a decline > or = 20 percent in forced expiratory volume in 1 second (FEV1), total lung capacity (TLC), or diffusion capacity for carbon monoxide (DLCO), were reassessed 5 months later. RESULTS: After chemotherapy, there were no significant changes in forced vital capacity (FVC; 111%+/-21% of the predicted value before chemotherapy vs. 111+/-20% of the predicted value after chemotherapy), FEV1 (108%+/-24% of the predicted value before chemotherapy vs. 107%+/-22% of the predicted value after chemotherapy), FEV1/FVC ratio (79%+/-8% before chemotherapy vs. 78%+/-6% after chemotherapy), alveolar volume (VA; 95%+/-14% of the predicted value before chemotherapy vs. 96%+/-14% of the predicted value after chemotherapy), or TLC (96%+/-14% of the predicted value before chemotherapy vs. 97%+/-13% of the predicted value after chemotherapy). In contrast, there was a significant decline in DLCO (101%+/-20% of the predicted value before chemotherapy vs. 96+/-21% of the predicted value after chemotherapy; P < 0.05). Arterial blood gas levels did not change after treatment. No patient had decreased FEV1 or TLC levels by > or = 20%, whereas 4 of 33 patients (12%) exhibited a substantial decline (> or = 20%) in DLCO that persisted 5 months after treatment (DLCO at baseline, immediately after chemotherapy, and 5 months after the completion of chemotherapy, respectively: 99%+/-36% of the predicted value vs. 75%+/-28% of the predicted value vs. 74%+/-31% of the predicted value; P < 0.05). None of the 33 patients developed respiratory symptoms or had radiologic signs suggestive of lung toxicity. Among the various risk factors examined, baseline DLCO and FEV1 levels were associated with changes in DLCO post-treatment. CONCLUSIONS: This prospective analysis showed that the combination of paclitaxel with carboplatin induced an isolated decrease in DLCO level in the absence of clinical or radiologic evidence of toxicity. Further studies are needed to clarify whether this reduction in DLCO is predictive of subsequent pulmonary impairment.
UI - 11724131
AU - Ozen H; Ekici S; Uygur MC; Akbal C; Sahin A
TI - Repeated transurethral resection and intravesical BCG for extensive superficial bladder tumors.
SO - J Endourol 2001 Oct;15(8):863-7
AD - Department of Urology, Hacettepe University School of Medicine, Ankara, Turkey.
PURPOSE: We report our experience with repeat transurethral resection (TUR) in a group of patients with superficial bladder tumors in whom complete resection in one session was impossible because of the extensive tumor burden. PATIENTS AND METHODS: Only the patients with such extensive (>10 g of resected tissue) tumors that we were unable to perform complete TUR initially were included in the present study. The patients underwent repeat TUR(s) 4 weeks after the previous one until complete resection of the tumor was achieved. After complete TUR, if the pathology examination confirmed superficial disease, the patients received intracavitery immunotherapy and were followed up thereafter. If pathology examination documented muscle-invasive disease, cystectomy was suggested. RESULTS: Of the 43 patients undergoing repeat TUR, 15 needed a second and 5 needed a third session to achieve complete resection. Of the patients, 28 (65%) had stage T1 and 15 (35%) has stage Ta tumor. Eight patients (19%) otherwise regarded as having superficial tumor were found to have muscle-invasive disease following repeat TURs. The mean follow-up of the remaining 35 patients with superficial disease was 34 months (range 1-126 months). Four of the patients with superficial disease progressed to T2 tumor. However, 16 patients achieved a state of complete response with no tumor recurrences during a mean of 38 months (range 4-126 month). The present protocol achieved bladder sparing in a total of 22 (63%) of the 35 patients with superficial disease. CONCLUSIONS: From the presented series, we suggest that one can use the combination of repeat TUR and intravesical immunotherapy in the management of bulky superficial bladder tumors in an effort to preserve the bladder.
UI - 11194623
AU - Neykov K; Donkov I; Mirchov R
TI - [Intravesical chemotherapy with mitomycin C after TUR for superficial bladder carcinoma]
SO - Khirurgiia (Sofiia) 1999;55(5):11-4
AD - Medical University, Department of Urology, Sofia, Bulgaria.
Fifty-four patients mean aged 58.5 years (28 women and 26 men) undergo transurethral resection for superficial bladder carcinoma. Postoperatively 20 mg mitomycin is administered by instillation into the bladder for 8 weeks. Preoperative assessment includes: complete blood count, urea, creatinine, isotope nephrography, ultrasonography, excretory urography and CT scan of pelvis. Multifocal lesions are diagnosed in 22 patients (40.7%). In 36 cases (66.7%) it is a matter of solitary papillomas. The distribution of lesions is as follows: left bladder wall--12 patients (22.2%), right bladder wall--13 (24.07 per cent), trigone--18 (33.3%), and anterior bladder wall--11 (20.03 per cent). Postoperative check-ups: cytological assessment of urine and regular endoscopic study at 3-6 months. Recurrence rate amounts to 42.5% for the maximum follow-up period.
UI - 11271984
AU - Baselli EC; Greenberg RE
TI - Maintenance therapy for superficial bladder cancer.
SO - Oncology (Huntingt) 2001 Jan;15(1):85-8; discussion 88-91
AD - Department of Urology, Temple University Hospital, Philadelphia, Pennsylvania, USA.
Transurethral resection remains the standard for first-line treatment of transitional cell carcinoma of the bladder. This technique clearly defines the pathologic grade and is essential in determining the clinical stage of the bladder tumor. Intravesical therapy is an important adjunct to transurethral resection in the management of patients with superficial bladder cancer, many of whom are at risk for disease recurrence and progression. Pharmacotherapy consisting of cytotoxic and immunomodulating agents has demonstrated utility against superficial transitional cell carcinoma. Bacillus Calmette-Guerin and mitomycin (Mutamycin) remain the more commonly used and most effective agents in the prophylaxis against recurrence and progression of superficial bladder transitional cell carcinoma. Many studies have examined their efficacy at different schedules. This article reviews the traditional intravesical agents that are useful in the therapy and prophylaxis of superficial transitional cell carcinoma of the bladder. It also addresses their long-term efficacy when used as maintenance therapy in higher-risk patients.
UI - 11932357
AU - Hara I; Miyake H; Hara S; Gotoh A; Okada H; Arakawa S; Kamidono S
TI - Optimal timing of radical cystectomy for patients with invasive transitional cell carcinoma of the bladder.
SO - Jpn J Clin Oncol 2002 Jan;32(1):14-8
AD - Department of Urology, Kobe University School of Medicine, Kobe, Japan.
OBJECTIVE: To determine whether the timing of radical cystectomy affects the survival of patients with invasive transitional cell carcinoma (TCC) patients underwent radical cystectomy in our institution. Among them, 50 patients who did not receive any perioperative therapies, including chemotherapy and radiotherapy, were divided into two groups, viz. 28 patients who underwent radical cystectomy within 3 months after the primary diagnosis of invasive bladder cancer (group A) and 22 who underwent radical cystectomy more than 3 months after the primary diagnosis (group B), and we then compared several clinicopathological factors and the survival between these two groups. RESULTS: No significant difference was observed in the patients' clinicopathological characteristics except for age between these two groups. The median follow-up periods for groups A and B were 53 and 48 months, respectively. In groups A and B, an average of 1.2 (range 1-2) and 1.4 (range 1-3) transurethral resections (TURs) of bladder cancer were performed, respectively (p = 0.83). Twenty of 28 patients in group A underwent orthotopic neobladder replacement, whereas only four of 22 underwent neobladder creation (p = 0.001). The recurrence-free, cause-specific and overall survival rates in group A were significantly higher than those in group B (p < 0.05, p < 0.05 and p < 0.05, respectively). Final pathological analysis revealed that the distributions of pathological stage, tumor grade and lymph node metastasis were similar between groups A and B; however, the incidence of vascular involvement in group B was significantly higher than that in group A (p < 0.05), despite the lack of a significant difference in the incidence of vascular involvement in TUR specimens between these two groups. CONCLUSIONS: These findings suggest that radical cystectomy in the early disease process, especially before the occurrence of vascular involvement, may result in the improvement of survival of patients with invasive TCC of the bladder.
UI - 11894003
AU - Stadler WM
TI - Gemcitabine doublets in advanced urothelial cancer.
SO - Semin Oncol 2002 Feb;29(1 Suppl 3):15-9
AD - Section Hematology/Oncology, Cancer Research Center, University of Chicago, Chicago, IL 60637, USA.
Gemcitabine was identified as an active agent in the treatment of urothelial cancer early in its clinical development. A gemcitabine/cisplatin regimen has been shown to lead to comparable survival in a phase III comparison to methotrexate/vinblastine/doxorubicin/cisplatin in the metastatic setting with less toxicity. Nonetheless, cisplatin-related toxicity is not inconsequential. Renal insufficiency limits wide applicability and long-term survival remains poor. A number of additional doublet combinations have thus been investigated. Substitution of carboplatin for cisplatin is feasible but leads to an apparent lower complete response rate. Likewise, combinations of gemcitabine and a taxane are feasible, but with somewhat discouraging response rates. A combination of doxorubicin and gemcitabine has been reported to lead to a 36% complete response rate, but this has not been confirmed. Combinations with targeted therapeutic agents such as the epidermal growth factor receptor inhibitors and trastuzumab have great potential, but the clinical studies have not yet been completed. Copyright 2002, Elsevier Science (USA). All rights reserved.
UI - 11894004
AU - Hussain M; Vaishampayan U; Smith DC
TI - Novel gemcitabine-containing triplets in the management of urothelial cancer.
SO - Semin Oncol 2002 Feb;29(1 Suppl 3):20-4
AD - Division of Hematology/Oncology, Wayne State University and the Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA.
Chemotherapy has been the cornerstone of treatment of advanced urothelial cancer. For a decade, the combination regimen of methotrexate/vinblastine/doxorubicin/cisplatin has been considered the standard for these patients. The need for improved efficacy and reduced toxicity of a predominantly palliative therapy has propelled efforts for new drug development. Of the newly identified agents with documented activity, both gemcitabine and paclitaxel have been evaluated with a platinum and have been incorporated into multiagent chemotherapy combinations. Phase II data from two gemcitabine-based triplets are currently available. Combination gemcitabine/paclitaxel/cisplatin and gemcitabine/paclitaxel/carboplatin have high levels of activity with overall and complete response rates of 76% and 26%, respectively, for the former and 68% and 32%, respectively, for the latter combination. The role of gemcitabine-based multiagent combinations compared with standard therapy awaits evaluation in prospectively randomized trials. Copyright 2002, Elsevier Science (USA). All rights reserved.
UI - 11894002
AU - von der Maase H
TI - Current and future perspectives in advanced bladder cancer: is there a new standard?
SO - Semin Oncol 2002 Feb;29(1 Suppl 3):3-14
AD - Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
The methotrexate/vinblastine/doxorubicin/cisplatin (MVAC) regimen has been the standard treatment in patients with locally advanced and metastatic urothelial cancer for the past 15 years. The minimal or moderate survival benefit-depending on prognostic features-and the severe toxicity associated with the MVAC regimen have made the search for new drugs and drug combinations of utmost importance to increase efficacy and/or decrease toxicity. In this respect, the taxanes and gemcitabine are promising new drugs. Paclitaxel and docetaxel as single agents have yielded overall response rates of 7% to 56%, depending on whether the patients have received prior chemotherapy for metastatic disease. The combination of paclitaxel and cisplatin has been explored in three studies with a total of 104 evaluable patients, a pooled overall response (OR) rate of 61%, and a complete response (CR) rate of 20%. There are two studies of docetaxel and cisplatin with a total of 91 evaluable patients, an OR rate of 54%, and a CR rate of 16%. The OR rate for paclitaxel and carboplatin in six studies was 43%, with a CR rate of 13%; however, the reported median survival was only 8.5 to 9.5 months. The OR rate for single-agent gemcitabine based on five studies was 26%, with a CR rate of 9%, which was apparently independent of whether the patients had received prior chemotherapy. The OR rate for gemcitabine and cisplatin in four phase II studies ranged from 41% to 57%, with a CR rate of 15% to 22% and a median survival of 12.5 to 14.3 months. Based on the encouraging results for the combination of gemcitabine and cisplatin (GC), a randomized phase III trial comparing GC and MVAC was begun in late 1996. This study of 405 randomized patients showed that the two regimens were associated with similar response rates, time to progression, and overall survival, whereas GC was associated with less toxicity than MVAC. On the basis of this superior risk-benefit ratio, the GC regimen should be favored as a new standard treatment in patients with locally advanced and metastatic urothelial cancer. Other promising combinations include gemcitabine and paclitaxel, with or without cisplatin, and the combination of ifosfamide, paclitaxel, and cisplatin. The triple combination of gemcitabine, paclitaxel, and cisplatin has yielded an OR rate of 78%, a CR rate of 28%, and a median survival of 24 months. An international phase III trial comparing this triple combination with GC in patients with locally advanced and metastatic urothelial cancer has now been initiated. Copyright 2002, Elsevier Science (USA). All rights reserved.
UI - 11894006
AU - Misset JL
TI - Brief communication: use of the multitargeted antifolate pemetrexed (Alimta) in genitourinary cancer.
SO - Semin Oncol 2002 Feb;29(1 Suppl 3):36-9
AD - Hopital St-Louis, Paris, France.
Pemetrexed (Alimta, LY231514) is a novel, multitargeted antifolate that is broadly active in a wide variety of solid tumors, including genitourinary malignancies. This agent has also shown clinically relevant activity in combination with other agents, including gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN). Further investigation is warranted in advanced disease and adjuvant settings. Copyright 2002, Elsevier Science (USA). All rights reserved.
UI - 8501821
AU - Theuer CP; FitzGerald DJ; Pastan I
TI - A recombinant form of Pseudomonas exotoxin A containing transforming growth factor alpha near its carboxyl terminus for the treatment of bladder cancer.
SO - J Urol 1993 Jun;149(6):1626-32
AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
The epidermal growth factor receptor (EGFR) is overexpressed on the superficial layers of malignant urothelium and is suspected of playing a role in tumor progression. TP40 is a chimeric protein composed of transforming growth factor-alpha (TGF alpha) fused to a modified form of Pseudomonas exotoxin A (PE) that is selectively cytotoxic to EGFR-bearing cells and is currently undergoing clinical study for the intravesical therapy of bladder cancer. We constructed a recombinant toxin PE35/TGF alpha-KDEL as an improved agent for the local therapy of EGFR-bearing bladder cancer. PE35/TGF alpha-KDEL does not require intracellular proteolysis to generate a carboxyl-terminal fragment capable of reaching the target cell cytosol and contains a modified carboxyl-terminal sequence KDEL, that increases toxin activity. These features make PE35/TGF alpha-KDEL from 10- to 700-fold more potent than TP40 on four human bladder cancer cell lines. PE35/TGF alpha-KDEL may be a useful agent for treatment of EGFR-bearing cancers.
UI - 10532707
AU - Pan CX; Koeneman KS
TI - A novel tumor-specific gene therapy for bladder cancer.
SO - Med Hypotheses 1999 Aug;53(2):130-5
AD - Department of Microbiology, Loyola University Medical Center, Maywood, IL 60153, USA. email@example.com
Gene therapy has been successfully used to treat genetic diseases. Currently, much investigation involves the role of gene therapy in malignant tumors. One problem associated with the retroviral system used for gene therapy is its non-specificity. Herein a vector delivery system is described, using human telomerase reverse transcriptase (hTRT) promotor, which can specifically affect telomerase-positive tumor cells while sparing nearby telomerase-negative cells. By combining a self-containing Cre/loxP site-specific recombination system into the design, this vector will destroy telomerase-positive, p53-negative tumor cells, while sparing normal cells which are telomerase-positive with wild type p53 (such as activated lymphocytes). This vector design appears especially suited to bladder transitional cell carcinoma, because of easy access transurethrally and high rate of local recurrence, and biologically secondary to high proportion of telomerase activity and p53 dysfunction.
UI - 11911292
AU - Hirano Y; Kageyama S; Ushiyama T; Suzuki K; Fujita K
TI - Clinical usefulness of chemotherapy based on an in vitro chemosensitivity test in urothelial cancer patients.
SO - Anticancer Res 2001 Nov-Dec;21(6A):4061-6
AD - Department of Urology, Hamamatsu University School of Medicine, Hamamatsu City, Japan. firstname.lastname@example.org
BACKGROUND: We evaluated the clinical usefulness of individualized chemotherapy based on an in vitro chemosensitivity test, i.e., the histoculture drug response assay (HDRA), for urothelial cancer. MATERIALS AND METHODS: 62 clinically obtained cancer specimens were studied. Each specimen was tested for sensitivity to nine anticancer drugs. The antitumor effect was calculated as the inhibition rate to their control values. The HDRA effective cytotoxic drugs were selected for clinical treatment. RESULTS: HDRA was possible in 58 out of 62 specimens (93.5%). Their chemosensitivity showed a wide variety even among the same histological category. No correlation was seen between histological grade and chemosensitivity. The effect of chemotherapy on the measurable lesions was studied in 12 patients and good clinical responses were obtained in 7 of them (58.3%). All 7 responders were the patients who received drugs predicted to be effective by HDRA. In 8 out of the 12 patients (66.7%), including 7 true-positive and 1 true-negative, HDRA correctly predlicted the clinical effect of chemotherapy. CONCLUSION: The HDRA might be feasible for predicting the efficacy and, therefore, selecting the proper anticancer drug for individual patients.
UI - 11899843
AU - Kaczmarek P; Buczynski A; Niemirowicz J; Gnitecki W; Kocur E; Karpinski
TI - J [Lipids peroxidation in platelets in patients with bladder cancer treated with Mycobacterium suspension]
SO - Pol Merkuriusz Lek 2001 Dec;11(66):484-6
AD - Oddzial Urologii Szpitala Ministerstwa Spraw Wewnetrznych i Administracji w Lodzi.
Platelet is blood's morphotic element in which intense energy metabolism takes place, which makes it possible to participate in the complex processes of the organism's homeostasis. The aim of the study was to analyse aerobic metabolism in the platelets, taking into consideration lipids peroxidation in patients with bladder cancer treated with the bacillus Calmette-Guerin (BCG) Mycobacterium suspension. The determination of superoxide dismutase (SOD-1) and malonyl dialdehyde (MDA) concentration activity constituted this evaluation's parameters. A group of 12 patients (4 women and 8 men) aged 54-67 years (average age 61) in which superficial bladder cancer was diagnosed were included in the study. Electroresection was carried out and subsequently, after 14 days, BCG Mycobacterium suspension was administered in intravesical instillations, in a 6-week cycle according to Morales. The material for the study was venous blood taken from the patients in three periods (before treatment, after the last clyster and 30 days after treatment) into the tubes with the addition of 1% EDTA in the ratio of 9 blood volumes to anticoagulant's one volume. Superoxide dismutase activity (Cu Zn--SOD) was determined according to Misra and Fridovich. The values were expressed in lamellar protein U/g protein. MDA concentration in platelet's TBARS was determined according to Pansa et al. MDA concentration included in TBARS was expressed in nmol/109 platelets. The controls were healthy volunteers in the same age range. In unaided studies a significant rise in superoxide dismutase (SOD-1) activity was obtained with the 1574.606 average before treatment > 2137.03 after treatment and 2646.4 after a month observation. Whereas MDA concentration increased in non-treated patients to 1.97, after treatment it dropped down significantly to 1.55 and sustained the downward trend after 30-day observation 1.4 nmol/109 platelets. The use of BCG intravesical clysters causes lipids peroxidation inhibition (decrease in MDA concentration) and the increase of SOD-1 activity results in smaller aggregation of platelets, preventing the formation of neoplastic metastases.
UI - 11730000
AU - Gilloteaux J; Jamison JM; Arnold D; Summers JL
TI - Autoschizis: another cell death for cancer cells induced by oxidative stress.
SO - Ital J Anat Embryol 2001;106(2 Suppl 1):79-92
AD - Department of Urology, Summa Health System, Akron, Ohio 44304, USA. email@example.com
Scanning and transmission electron microscopy (SEM and TEM) were employed to characterize the cytotoxic effects of vitamin C (VC), Vitamin K3 (VK3) or a VC:VK3 combination on a human bladder carcinoma cell line (T24) following vitamin treatment. T24 cells exposed to VC alone showed membrane defects. VK3-treated cells show greater damage than VC treated cells because they exhibit membrane defects, cytoskeletal damage, excision of cytoplasm, and a substantial decrease in the number of viable cells. VC: VK3 treatment exacerbates the damages, especially intranuclear and nucleolar and induces an extreme reduction of cell size by cytoplasmic self-excision. Conversely, the nuclear envelope remains intact and the rough endoplasmic reticulum (RER) maintains its integrity until karyorrhexis occurs through a new phenomenon of cell death that we have named "autoschizis". From our morphological studies and previous biochemical reports on the topic, we are able to propose that this autoschizic cell death found is induced by oxidative stress.
UI - 11956428
AU - Solsona E; Iborra I; Ricos JV; Monros JL; Rubio J; Almenar S
TI - Clinical panurothelial disease in patients with superficial bladder tumors: therapeutic implications.
SO - J Urol 2002 May;167(5):2007-11
AD - Departments of Urology and Pathology, Instituto Valenciano de Oncologia, Valencia, Spain.
PURPOSE: We established the prognostic and therapeutic implications of panurothelial involvement in patients with superficial bladder tumors for optimizing therapeutic approaches in those at risk for panurothelial involvement. MATERIALS AND METHODS: We studied the records of 35 patients with clinical panurothelial disease. Since all of these patients presented with high risk superficial bladder cancer during followup, they were included in specific therapeutic and followup regimens. Radical procedures or conservative therapies were indicated mainly according to pathological examination and the recurrence pattern. RESULTS: Panurothelial involvement was a late stage of a recurrent and diffuse process that essentially developed in sequences, in which all patients presented with high risk superficial bladder tumors. This process involved continued relapse after panurothelial involvement developed. Notably 19 patients (79.1%) at risk for recurrence had repeat relapse in the urothelium. In the upper urinary tract 12 patients (34.3%) had bilateral involvement, including 7 (41.2%) of 17 patients after cystectomy. We identified 2 subgroups of patients. The subgroup with a better prognosis included 27 patients in whom late panurothelial disease developed step by step after a complete response to intravesical therapy, including 14 (51.8%) who were free of disease. The other subgroup with a poor prognosis included 8 patients with concurrent bladder carcinoma in situ and prostate involvement as well as early panurothelial disease, of whom only 2 (25%) were disease-free. All patients underwent many therapeutic approaches. A mean of 7.5 surgical procedures per patient were done, including a mean of 5.5 transurethral resections, a mean of 1 conservative approach to the upper urinary tract and a mean of 1.1 radical procedures. At a median followup of 111 months 10 patients (28.5%) were disease-free but only 7 (20%) retained the bladder, while 19 (54.3%) died of tumor. CONCLUSIONS: Patients with high risk superficial bladder multifocal tumors and associated bladder carcinoma in situ are at high risk for panurothelial involvement. Radical cystectomy may be recommended in these patients when initially or during followup, concurrent high risk superficial bladder tumors and prostate involvement develop or prostate involvement recurs. For the upper urinary tract conservative therapies may be advisable when noninfiltrating tumors are diagnosed even after cystectomy due to the high rate of bilateral new onset disease. When cystectomy is performed, extended excision of the upper urinary tract and pyelo-intestinal anastomosis may be considered.
UI - 11956429
AU - Chang SS; Cookson MS; Baumgartner RG; Wells N; Smith JA Jr
TI - Analysis of early complications after radical cystectomy: results of a collaborative care pathway.
SO - J Urol 2002 May;167(5):2012-6
AD - Department of Urologic Surgery and Patient Care Services, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2765, USA.
PURPOSE: We examined our recent series of patients who underwent radical cystectomy to determine and analyze the early perioperative morbidity of the procedure in a contemporary series treated with the guidance of a clinical pathway. MATERIALS AND METHODS: We reviewed the records of 304 within 30 days of the procedure. Potential variables predictive of early morbidity were analyzed, including patient age, gender, race, American Society of Anesthesiologists score, type of urinary diversion, smoking history, estimated blood loss, transfusion requirement, pathological stage and operative time. RESULTS: The overall minor complication rate was 30.9% (94 of 304 patients). Postoperative ileus was the most common minor complication, affecting 54 patients (18%). Increased blood loss and major complications predicted a significantly higher likelihood of ileus on multivariate analysis (p = 0.02 and 0.001, respectively). Major complications in 15 patients (4.9%) correlated with higher American Society of Anesthesiologists score, surgical intensive care unit admission and transfusion requirement (p = 0.01, <0.001 and 0.001, respectively). The early mortality rate was 0.3% (1 patient). CONCLUSIONS: Within the framework of a clinical pathway, radical cystectomy can be performed safely with an acceptable rate of early minor and major complications. Delay in the return of bowel function is the most common minor complication. Increased estimated blood loss, transfusion requirement and a major complication predicted a higher likelihood of postoperative ileus. The acceptable rate of early morbidity in this series in a 5-year period validates its use in patients undergoing radical cystectomy.
UI - 11956438
AU - Wammack R; Wricke C; Hohenfellner R
TI - Long-term results of ileocecal continent urinary diversion in patients treated with and without previous pelvic irradiation.
SO - J Urol 2002 May;167(5):2058-62
AD - Department of Urology, University of Mainz School of Medicine, Mainz, Germany.
PURPOSE: Patients who receive pelvic irradiation may require urinary diversion to manage complications resulting from progressive malignancy or radiotherapy. The choice of urinary diversion is an important issue and remains controversial. We characterized the long-term outcome of urinary diversion with a continent ileocecal reservoir in patients who received pelvic irradiation versus those who underwent urinary diversion without previous irradiation. MATERIALS AND METHODS: Continent urinary diversion with an ileocecal reservoir (Mainz pouch 1) was performed in 36 irradiated patients in a 9-year period. Morbidity, mortality, the reoperative rate and parameters associated with the surgical procedure were determined at a median followup of 57 months. Results were compared with those in 385 nonirradiated patients who received the same type of continent diversion after cystectomy for bladder cancer. RESULTS: Irradiated patients had a significantly higher rate of serious complications after ileocecal urinary diversion than nonirradiated controls. Continence mechanism failure occurred in 25% of patients in the irradiated group and 5.7% in nonirradiated patients, stomal complications were noted in 38.8% and 10.6%, and ureteral complications developed in 22.2% and 6.5%, respectively. CONCLUSIONS: In patients who have received pelvic radiotherapy, ileocecal Mainz pouch 1 continent urinary diversion is associated with a high rate of serious complications and should be avoided.
UI - 11547071
AU - Smith E; Yoon J; Theodorescu D
TI - Evaluation of urinary continence and voiding function: early results in men with neo-urethral modification of the Hautmann orthotopic neobladder.
SO - J Urol 2001 Oct;166(4):1346-9
AD - Department of Urology, University of Virginia Health Sciences Center, Charlottesville, Virginia, USA.
PURPOSE: At our institution we use the Hautmann orthotopic bladder replacement with a chimney and neo-urethral modification. A neo-urethral tube allows tension-free intestino-urethral anastomosis, thus providing application of this procedure for patients who may otherwise not qualify due to the inability of the small bowel to reach the urethra. However, this neo-urethral tube may also enhance continence by providing significant intra-abdominal urethral length. Conversely, such a modification may be associated with a higher degree of urinary retention. Early evaluation and reporting on the results of this and urinary reconstruction with Hautmann repair using chimney and neo-urethral modifications. We performed a retrospective analysis of urinary function and continence with data obtained from patient questionnaires completed preoperatively and at each postoperative office visit. The examining physician chart notes were reviewed for information about urinary retention. The American Urological Association symptom score and voiding bother index were used to assess urinary function and bother, respectively. Urinary continence was defined as the complete absence of any form of urinary leakage protection. RESULTS: Of the 14 patients 12 were completely continent day and night, with a median followup of 17 months. There were 2 patients who wore pads less than 7 months after surgery. Improvement of urinary continence appeared to continue up to 12 months postoperatively. Despite this encouraging effect, when our data were compared to the published literature, we noted a somewhat increased incidence of patients requiring clean intermittent catheterization to manage significant post-void urinary residuals. We had no patients with urethro-intestinal strictures who required clean intermittent catheterization. CONCLUSIONS: The neo-urethral tube modification appears to have a significant and favorable impact on urinary continence while seeming to be associated with a trend towards an increased rate of chronic urinary retention. Longer followup will be required to determine whether this higher rate of chronic urinary retention will remain stable or change with time.
UI - 11857030
AU - Hayes GM; Carpenito C; Davis PD; Dougherty ST; Dirks JF; Dougherty GJ
TI - Alternative splicing as a novel of means of regulating the expression of therapeutic genes.
SO - Cancer Gene Ther 2002 Feb;9(2):133-41
AD - Department of Radiation Oncology, UCLA Center for Health Sciences, Los Angeles, California 90095-1724, USA.
In order to determine the potential of alternative splicing as a means of targeting the expression of therapeutic genes to tumor cells in vivo, a series of episomal plasmid-based "splice-activated gene expression" (pSAGE) vectors was generated, which contain minigene cassettes composed of various combinations of the three alternatively spliced exons present in the differentially expressed adhesion protein CD44R1 (v8, v9, and v10) with or without their corresponding intronic sequences, positioned in-frame between the CD44 leader sequence and a "leaderless" human liver/bone/kidney alkaline phosphatase (ALP) cDNA. Because both the v8-v9 and v9-v10 introns contain multiple in-frame stop codons, the expression and enzymatic activity of ALP are dependent upon the accurate removal of intronic sequences from the pre-mRNA transcripts encoded by these constructs. The various pSAGE constructs were introduced into CD44H-positive (T24) and CD44R1-positive (PC3) target cells by electroporation and transfectants selected in hygromycin B. ALP expression was determined by staining with the ALP substrate, BCIP/INT, and the transfected cells tested for their sensitivity to the inactive prodrug, etoposide phosphate. ALP-mediated dephosphorylation of etoposide phosphate generates the potent topoisomerase II inhibitor etoposide. The data obtained indicate that whereas the v8-v9 intron is spliced in both CD44H- and CD44R1-positive cells, the v9-v10 intron is efficiently and accurately removed only in CD44R1-positive cells. Furthermore, only CD44R1-positive cells were sensitized to etoposide phosphate when transfected with the v9-v10.ALP construct. These data emphasize the potential usefulness of alternative splicing as a novel means of targeting gene expression to tumor cells in vivo.
UI - 11876754
AU - Pages F; Lebel-Binay S; Vieillefond A; Deneux L; Cambillau M; Soubrane
TI - O; Debre B; Tardy D; Lemonne JL; Abastado JP; Fridman WH; Thiounn N Local immunostimulation induced by intravesical administration of autologous interferon-gamma-activated macrophages in patients with superficial bladder cancer.
SO - Clin Exp Immunol 2002 Feb;127(2):303-9
AD - Hopital Europeen Georges Pompidou, Service d'Immunologie Biologique, Unite INSERM 255, France. Franck.PAGES@hop.egp.ap-hop-paris.fr
We conducted a phase I/II clinical trial of the safety and efficacy of intravesical administration of autologous IFN-gamma-activated macrophages (MAK) in patients with superficial bladder cancer. Monocyte-derived MAK cells were prepared in vitro and patients received six instillations of 1.4 x 10(8) to 2.5 x 10(8) cells, once a week, for five consecutive weeks. Treatment was well tolerated, with seven grade 1 and five Grade 2 protocol-related adverse effects. Nine out of 17 included patients had no recurrences during the year following the first instillation of MAK. The aim of the present study was to search for immune parameters related to local immunostimulation induced by MAK. Monitoring of the patients showed that urinary IL-8, GM-CSF and, to a lesser extent, IL-18 were increased following MAK instillations, with inter-individual differences. The urinary IL-8 level was about 10-fold higher than that observed for other cytokines, and its biological activity was reflected by a concomitant increase of urinary elastase, indicating neutrophil activation and degranulation. We also showed that nine out of 12 patients investigated presented an increase of urinary neopterin, a marker of IFN-gamma-activated macrophages, 7 days after MAK instillation, while serum neopterin levels were almost stable. These results are in line with persistence of activated macrophages in the bladder wall after infusions. Moreover, there was evidence of macrophages in urine smears 2 months after the sixth MAK instillation, and the score of macrophages correlated with the quantity of neutrophils in the urine. Overall, this study provides evidence of a local immunostimulation induced by this novel and safe immunotherapeutic approach of MAK instillations in patients with superficial bladder cancer.
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