Treatment Of Superficial Bladder Carcinoma Research Articles

One-shot intravesical instillation of the mucous adhesive anticancer agent hydroxypropylcellulose-doxorubicin for the treatment of superficial bladder carcinoma is sufficient to determine antitumor effects.

A 20 mg/20 ml dose of the membrane adhesive anticancer preparation, hydroxypropylcellulose-doxorubicin (HPC-doxorubicin), was instilled into urinary bladders through a catheter for the treatment of superficial bladder carcinomas (Ta-T1). After 14-30 days, the effects of the drug on tumors was examined by cystoscopy, and the residual tumor tissue where reduction in size was observed was resected by transurethral resection (TUR). Therapeutic effects were as follows: a complete response (CR) was found in 6 cases (37.5%), a reduction in size of more than 50% (partial response = PR) in 4 cases (25%), and a less than 25% reduction (no change = NC) in 6 cases (37.5%). In no case was progression of the disease noted. In CR cases, cold cup punch biopsy revealed no tumor cells remaining at the site where the tumor was present before the instillation. Side effects such as bladder irritation were found in 4 cases, but they were only temporary in nature. The one-dose HPC-doxorubicin approach developed by ourselves allowed detection of antitumor effects between 14 and 30 days after the instillation and therefore determination of sensitivities at an earlier stage than with instillation of the conventional water-soluble type of doxorubicin hydrochloride.

Treatment of superficial bladder carcinoma in private practice

Until the mid-1950s, patients with superficial bladder carcinoma were routinely treated with repeat electrocoagulation. Several new developments revolutionized the management of this malignancy, including the introduction of ileal conduits, the growing use of radiotherapy and total cystectomy for the treatment of carcinoma with muscle invasion, the availability of thiotepa, and the development of flexible cystoscopes. Today, the spectrum of chemotherapeutic and immunotherapeutic agents for the treatment of superficial bladder cancer has expanded and a variety of agents are available, each characterized by a distinct therapeutic and side effect profile. The indications for the use of intravesical therapy and guidelines for patient follow-up are outlined. A favorable therapeutic outcome (including good patient compliance) also depends in large part on the degree to which the practitioner provides adequate patient reassurance and education, and encourages dialogue. Personal experience in the private practice setting suggests that the combination of good interpersonal communication and the use of an effective and well-tolerated agent, such as mitomycin, ensures a positive prognosis for most patients with superficial bladder carcinoma.

Hypersen sitivity Systemic Reaction Following Intravesical Bacillus Calmette-Guerin: Successful Treatment With Steroids

Intravesical bacillus Calmette-Guerin (BCG) is an effective treatment for superficial bladder carcinoma. Serious complications, including disseminated BCG infection, are infrequent. We report a case of granulomatous hepatitis with pneumonitis following intravesical administration of BCG. Cultures for mycobacteria were negative in sputum, bronchoalveolar lavage, liver and blood specimens. All symptoms disappeared within days after steroid therapy. Hypersensitivity reaction should be considered in patients with systemic symptoms after immunotherapy with BCG.

Immunophenotypic characterization of the bladder mucosa infiltrating lymphocytes after intravesical BCG treatment for superficial bladder carcinoma.

The lymphocytes infiltrating the bladder mucosa of 28 patients treated with bacillus Calmette-Guérin (BCG) for superficial bladder carcinoma were characterized using an immunohistochemical technique on frozen sections of biopsy specimens obtained during cystoscopy. The inflammatory response induced by BCG consisted mainly of T lymphocytes (CD3+), most of which had the helper/inducer phenotype (CD4+), with a CD4/CD8 ratio greater than 1. A minor subset of lymphocytes were of B phenotype (CD22+). These findings persisted for the whole follow-up period (6-12 months) in spite of a progressive decrease of the inflammatory infiltrate. No difference in the lymphocyte phenotype was observed between nonresponding patients and those who responded to BCG in the short term. It is concluded that, although intravesical BCG therapy does affect the immunocompetent cells of the bladder wall, the BCG-induced antitumor activity is unlikely to depend exclusively on a local immune mechanism.

Superficial bladder cancer: diagnosis, surveillance and treatment.

Approximately 70% of all bladder cancers are superficial at the time of presentation. Superficial bladder cancer includes tumors confined to the urothelium (clinical stage Ta) or lamina propria (stage T1) and flat carcinoma in situ (stage Tis). Because the biological behavior of bladder neoplasms is variable, several important prognostic factors must be addressed. Multivariate analyses have shown that factors predictive of tumor recurrence and tumor progression include multifocal tumors, high grade tumors, T1 tumors and positive urinary cytology after transurethral resection (TUR). The patient with superficial bladder cancer should be monitored via endoscopy supplemented by urinary cytology, using either voided or bladder irrigation specimens and urinalysis. Frequent intravenous urography is not required, even in high grade tumors, as long as the clinical and pathologic studies remain negative and the patient is asymptomatic. The "gold standard" of treatment for superficial bladder carcinoma is TUR of the entire tumor. Despite TUR, new tumors will occur in approximately 50% of all patients; those at highest risk for tumor recurrence and progression require adjuvant intravesical therapy after TUR. A variety of drugs are used as intravesical therapy, including thiotepa, mitomycin C, doxorubicin hydrochloride, Bacillus Calmette-Guerin (BCG), epirubicin, and interferon. Although associated with the most toxicity, BCG appears to be the most efficacious agent in increasing the time to recurrence and progression and in reducing the recurrence rate.

表在性膀胱腫瘍に対する Verapamil 併用 HPC-adriamycin の膀胱内注入療法

A new form of hydroxypropylcellulose-adriamycin (HPC-ADM), which was supplemented with verapamil, a known calcium antagonist, in order to potentiate the antineoplastic effect of HPC-ADM, was synthesized and used for the treatment of superficial bladder carcinoma for clinical evaluation. The results are reported in this paper. A total of 23 patients who were treated for bladder carcinoma during a 2-year period (1987-1988) were subjected in this study. All patients were diagnosed cases of superficial bladder carcinoma as follows; Ta, 3 cases, T1, 18 cases and Tis, 2 cases. For the injection protocol, firstly HPC-ADM solution supplemented with verapamil was introduced into the urinary bladder via the urethra. After 2-3 weeks, the efficacy of the drug against the tumor was evaluated by cystoscope. Patients in whom the drug were found to be effective received increased administration of drug. In cases in whom the drug was found to be ineffective, different drugs for further treatment were adopted. The average frequency and amount of drug was 2.3 times and 45.2 mg, respectively. Complete responses achieved in 9 of 23 cases (39.1%). Of the 23 cases, 4 cases was with PR and 10 with NC. No cases were found to be with PD. Side effects were observed in 4 of the 23 cases (17.4%), however, severe side effects were not recognized. The important aspect in applying the method of intravesical therapy is that it makes enhanced antineoplastic potency possible with concomitant reduction of side effects and prevents the invasion of tumor.

Systemic Bacillus-Calmette Guerin Infection after Transurethral Administration for Superficial Bladder Carcinoma

It is well known that intravesical bacillus Calmette-Guerin therapy is a safe and effective treatment for superficial bladder carcinoma with few serious complications. However, we report a case of pneumonitis, hepatitis, azotemia, fever and pancytopenia in a patient after transurethral administration of bacillus Calmette-Guerin. Even though severe systemic complications are rare, patients who have high fevers or signs of other systemic manifestations require documentation of the extent of the infection. Also, we address the use of prophylactic antituberculous drugs, not only to prevent these symptoms but also to raise the questions of diminishing the immunological effect of the treatment.

Monitoring Intravesical Bacillus Calmette-Guerin Treatment of Superficial Bladder Carcinoma by Postoperative Urinary Cytology

We studied 51 patients with superficial bladder carcinoma who had been treated with transurethral resection of all gross tumor followed by intravesical bacillus Calmette-Guerin weekly for 6 weeks. Within 72 hours of either the first or second quarterly cystoscopic surveillance examination after bacillus Calmette-Guerin therapy, a conventional cytology study was obtained. Of these patients 8 (15.7 per cent) had positive, 9 (17.6 per cent) suspicious and 34 (66.7 per cent) negative postoperative cytology studies. Subsequent tumor recurrence was defined as a positive biopsy or visible papillary tumors on cystoscopic examination. All 8 patients with a positive postoperative cytology study had tumor recurrence at a median interval of 4 months. Of the 9 patients with a suspicious study 7 (77.8 per cent) had recurrent tumor at a median interval of 7 months and 2 (22.2 per cent) had no evidence of disease at 16 and 19 months, respectively. Of the 34 patients with a negative postoperative cytology study 13 (38.2 per cent) had tumor recurrence after a median interval of 4 months and 21 (67.8 per cent) had no evidence of disease after a median of 25 months. The tumor recurrence rate in patients with a positive or suspicious postoperative cytology study was significantly greater than that of patients with a negative study (p equals 0.001, Fisher’s exact test). Postoperative cytology appears to be a significant prognostic indicator following transurethral resection and intravesical bacillus Calmette-Guerin treatment of superficial bladder carcinoma.

Monitoring Endoscopic Treatment of Superficial Bladder Carcinoma by Postoperative Urinary Cytology

Transurethral resection was the only modality of treatment in 39 patients with long-standing, recurrent, superficial bladder carcinoma. Postoperative urinary cytology was performed within 3 days of each endoscopy. Tumor recurrence was defined by the presence of a positive biopsy or visible papillary tumors on followup cystoscopic examination. Tumor recurred in 38 patients (97.4 per cent) and 1 patient (2.6 per cent) has remained free of disease 74 months following transient positive postoperative cytology. Among the 38 recurrences 15 (39.5 per cent) were positive, 3 (7.9 per cent) suspicious and 20 (52.6 per cent) negative at the postoperative cytological examination. The interval to recurrence did not differ significantly among the 3 groups. The failure of a negative postoperative cytology study to predict a durable response to treatment by transurethral resection reflects the polychronotopic nature of superficial bladder tumors in this select patient population and suggests the need for adjuvant therapy.

Biological potentials of interferons relevance in the systemic treatment of superficial bladder carcinoma

Interferons (IFN) are a class of glycoproteins which have antiviral, antiproliferative and immunomodulating properties. Three major classes of IFN are characterized today on the basis of antigenic and physical-chemical properties. They modulate various immunological functions and can be characterized as biological response modifiers. In addition, they have direct cytotoxic effects on tumor cells. Since 1978, interferons have been in clinical use as antineoplastic agents in patients with superficial bladder tumors. The first reports on the treatment of superficial bladder tumors with natural IFN preparations offered encouraging results. Recently published data with systemically applied recombinant IFN alpha-2, however, did not confirm the good results previously reported. One of the reasons for these conflicting results might be the different types of IFN alpha used. Since laboratory results have demonstrated that reduction of the tumor cell multiplication rate can be influenced by the concentration of IFN, topical application, e.g. in the therapy of superficial bladder carcinoma, may offer more promising results in comparison to systemic application. Further knowledge on the immunomodulatory and anticellular mechanisms is needed in order to allow a successful application of IFN in the treatment of cancer.

Intravesical treatment of superficial bladder carcinoma with interferons

The high incidence of tumor recurrence and the multifocal occurrence of superficial bladder carcinoma have stimulated the idea of intracavitary treatment for therapy and prophylaxis. However, all potent agents have been shown to exhibit severe side effects. Interferons (IFN) are known to inhibit the proliferation of various bladder carcinoma cell lines in vitro. In this study the efficacy of topical administration of IFN was investigated in 10 patients with recurrent superficial bladder carcinoma without evidence of local or distant metastases. The patients had had 1–6 tumor recurrences prior to treatment. Starting 5–8 days following transurethral resection, 5×107 IU IFN alpha-2 (arg) were given intravesically twice a week for 6 weeks. The first examination, including cystoscopy and cytological evaluation of urine, was performed 6 weeks later. Except for occasional urinary tract infections, no side effects were observed. At the first follow-up examination 3 months following the beginning of treatment, tumor recurrence was observed in 6 out of 10 patients. In these patients there was no change regarding tumor stage and grade prior to and following IFN treatment. Since in vitro investigations have demonstrated a correlation between IFN receptor status and growth inhibition, determination of IFN receptors in the membrane of bladder carcinoma might be helpful to those patients who could benefit from IFN treatment.

Role of immunotherapy in the prevention of recurrence and invasion of urothelial bladder tumors: a review

Although many different chemotherapeutic regimens for the treatment of superficial bladder cancer have been used, none are considered ideal. This has stimulated investigations of alternative forms of therapy, including immunotherapy. Contained within this therapeutic category are bacterial agents such as Bacille Calmette-Guerin, Corynebacterium parvum and a streptococcal preparation, OK-432, as well as the interferon inducer polyriboinosinic acid-polyribocytidylic and passive immunotherapy with sensitized pig lymphocytes. With the exception of BCG, most forms of immunotherapy have not been been effective in the treatment of superficial bladder carcinoma. This paper reviews immunotherapy with emphasis on the studies of BCG as prophylaxis against and treatment for superficial transitional cell carcinoma of the bladder.

Carcinoma in Situ of Bladder: Clinico-Pathologic Study of Case with a Suggested Approach to Detection

No AccessJournal of Urology1 Oct 1966Carcinoma in Situ of Bladder: Clinico-Pathologic Study of Case with a Suggested Approach to Detection M.R. Melamed, H. Grabstald, and W.F. Whitmore M.R. MelamedM.R. Melamed More articles by this author , H. GrabstaldH. Grabstald More articles by this author , and W.F. WhitmoreW.F. Whitmore More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(17)63292-0AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail © 1966 by The American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byBadalament R, Gay H, Cibas E, Herr H, Whitmore W, Fair W and Melamed M (2018) Monitoring Endoscopic Treatment of Superficial Bladder Carcinoma by Postoperative Urinary CytologyJournal of Urology, VOL. 138, NO. 4 Part 1, (760-762), Online publication date: 1-Oct-1987.Badalament R, Gay H, Cibas E, Herr H, Whitmore W, Fair W and Melamed M (2018) Monitoring Intravesical Bacillus Calmette-Guerin Treatment of Superficial Bladder Carcinoma by Postoperative Urinary CytologyJournal of Urology, VOL. 138, NO. 4 Part 1, (763-765), Online publication date: 1-Oct-1987.Kano M and Iwasaki H (2018) Non-Papillary Carcinoma in Situ of the Bladder: A Clinicopathologic Study of 2 Cases Treated With Radical CystoprostatourethrectomyJournal of Urology, VOL. 122, NO. 1, (116-120), Online publication date: 1-Jul-1979.Althausen A, Prout G and Daly J (2018) Non-Invasive Papillary Carcinoma of the Bladder Associated with Carcinoma in SituJournal of Urology, VOL. 116, NO. 5, (575-580), Online publication date: 1-Nov-1976.Skinner D, Richie J, Cooper P, Waisman J and Kaufman J (2018) The Clinical Significance of Carcinoma in Situ of the Bladder and its Association with Overt CarcinomaJournal of Urology, VOL. 112, NO. 1, (68-71), Online publication date: 1-Jul-1974.Melicow M (2018) Tumors of The Bladder: A Multifaceted ProblemJournal of Urology, VOL. 112, NO. 4, (467-478), Online publication date: 1-Oct-1974.Thelmo W, Seemayer T, Madarnas P, Mount B and Mackinnon K (2018) Carcinoma in Situ of the Bladder with Associated Prostatic InvolvementJournal of Urology, VOL. 111, NO. 4, (491-494), Online publication date: 1-Apr-1974.Kern W, Bales C and Webster W (2018) Cytologic Evaluation of Transitional Cell Carcinoma of the BladderJournal of Urology, VOL. 100, NO. 5, (616-622), Online publication date: 1-Nov-1968. Volume 96Issue 4October 1966Page: 466-471 Advertisement Copyright & Permissions© 1966 by The American Urological Association Education and Research, Inc.MetricsAuthor Information M.R. Melamed More articles by this author H. Grabstald More articles by this author W.F. Whitmore More articles by this author Expand All Advertisement PDF downloadLoading ...