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Abramson Cancer CenterNCI CANCERLIT® Search: Therapy of Bladder Cancer - April 2002
National Cancer Institute®
Last Modified: April 1, 2002
Table of Contents
1
UI - 11905732
AU - Orellane C
TI -
St John's wort helps to fight bladder cancer.
SO - Lancet Oncol 2001 Jul;2(7):399
2
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. idimo@otenet.gr
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.
3
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.
4
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.
5
UI - 11927341
AU - Soloway MS
TI -
Progression and survival in patients with T1G3 bladder tumors.
SO - Urology 2002 Apr;59(4):631; discussion 631
6
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.
7
UI - 11589061
AU - Huncharek M; Kupelnick B
TI -
Chemotherapeutic prophylaxis of superficial bladder tumors.
SO - Oncology (Huntingt) 2001 Sep;15(9):1106
8
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.
9
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.
10
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.
11
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.
12
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.
13
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.
14
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. cpan1@wpo.it.luc.edu
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.
15
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. hirano@hama-med.ac.jp
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.
16
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.
17
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.
jagillot@prodigy.net
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.
18
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.
19
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.
20
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.
21
UI - 11956495
AU - Droller MJ
TI -
Chemoradiotherapy for muscle invading bladder carcinoma. Final report of
a single institutional organ-sparing program.
SO - J Urol 2002 May;167(5):2297-8
22
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.
23
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.
24
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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