Integrative tumor board: transitional cell carcinoma of the bladder.
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Aged↗
Biomedical subjects
Donald L Lamm
Publications and source records attributed to Donald L Lamm.
Bladder cancer: current optimal intravesical treatment.
Superficial bladder cancer can be treated surgically, but patients are at high risk for recurrence. Tumors are categorized as low, intermediate, and high-risk based on grade, stage, and pattern of recurrence. Low-risk tumors are best treated with a single instillation of chemotherapy (thiotepa, doxorubicin, or mitomycin) (Lamm, 2002). Though effective, the toxicity of bacillus Calmette-Guerin immunotherapy (BCG) restricts its use to treat higher-grade tumors. Intermediate risk tumors can be treated with chemotherapy as well, but will often require immunotherapy. High-risk tumors are best treated with intravesical BCG using a 3-week maintenance schedule. Side effects of BCG immunotherapy can be decreased by logarithmic reductions in dose. Patients who fail BCG may be rescued with BCG plus interferon alfa or radical cystectomy.
Adjuvants, Immunologic↗
Superficial bladder cancer therapy.
Bladder cancer treatment remains a challenge despite significant improvements in preventing disease progression and improving survival. Intravesical therapy has been used in the management of superficial transitional cell carcinoma (TCC) of the urinary bladder (i.e. Ta, T1, and carcinoma in situ) with specific objectives which include treating existing or residual tumor, preventing recurrence of tumor, preventing disease progression, and prolonging survival. The initial clinical stage and grade remain the main determinant factors in survival regardless of the treatment. Prostatic urethral mucosal involvement with bladder cancer can be effectively treated with Bacillus Calmette-Guerin (BCG) intravesical immunotherapy. Intravesical chemotherapy reduces short-term tumor recurrence by about 20%, and long-term recurrence by about 7%, but has not reduced progression or mortality. Presently, BCG immunotherapy remains the most effective treatment and prophylaxis for TCC (Ta, T1, CIS) and reduces tumor recurrence, disease progression, and mortality. Interferons, Keyhole-limpet hemocyanin (KLH), bropirimine and Photofrin-Photodynamic Therapy (PDT) are under investigation in the management of TCC and early results are encouraging. This review highlights and summarizes the recent advances in therapy for superficial TCC.
Administration, Intravesical↗
Antitumor activity of common antibiotics against superficial bladder cancer.
OBJECTIVES: The recurrence rate for superficial bladder tumors treated with complete resection averages 88%. Intravesical chemotherapy decreases the recurrence rate by only 14%; thus, new chemotherapeutic agents are needed. Antibiotics are often used to prevent infections after transurethral resection of bladder tumors. Oral intake of antibiotics results in significantly greater concentrations in the urine than in the serum. Our objective was to evaluate four commonly used urinary antibiotics for their cytotoxic activity against bladder cancer cells at clinically relevant concentrations. METHODS: Three human transitional cell carcinoma lines--HTB9 (grade 2), T24 (grade 3), and TccSup (grade 4)--were exposed to ciprofloxacin, trimethoprim-sulfamethoxazole, cefazolin, or nitrofurantoin at concentrations from 0 (control) to 1000, 1000, 5000, and 2000 microg/mL, respectively, for 96 hours. Cytotoxicity was evaluated using the MTT colorimetric assay. Six replicates were used for each data point, and the results are reported as the mean +/- standard deviation. RESULTS: Significant cytotoxicity (P <0.001) was seen, starting at 12.5 microg/mL (HTB9, TccSup) and 50 microg/mL (T24) for ciprofloxacin, 31.25 microg/mL (HTB9, TccSup) and 62.5 microg/mL (T24) for trimethoprim-sulfamethoxazole, 19.5 microg/mL (HTB9) and 156.3 microg/mL (T24, TccSup) for cefazolin, and 7.8 microg/mL (HTB9, T24, TccSup) for nitrofurantoin. Cytotoxicity was dose dependent for all four antibiotics, and the maximal effect did not differ among antibiotics. CONCLUSIONS: Commonly used antibiotics exhibit significant dose-dependent cytotoxicity against bladder cancer cells at concentrations achievable in the urine after oral administration. The administration of antibiotics after transurethral resection of bladder tumors might prevent seeding of cancer cells and thereby decrease the recurrence rate. Preclinical data such as these must be considered in the design of clinical trials addressing recurrence after transurethral resection of bladder tumors.
Antibiotics, Antineoplastic↗
Complications of laparoscopic nephrectomy: the Mayo clinic experience.
PURPOSE: We present the incidence of complications and conversions during laparoscopic nephrectomy performed for various indications and discuss methods to help prevent future complications. MATERIALS AND METHODS: From June 1999 to February 2003 at our institution 285 laparoscopic nephrectomy cases were performed, consisting of 113 radical nephrectomies, 101 donor nephrectomies, 27 simple nephrectomies, 23 partial nephrectomies and 21 nephroureterectomies. We reviewed the data base of patients who underwent laparoscopic nephrectomy to examine complications and analyze factors related to conversion to an open surgical procedure. RESULTS: Major complications occurred in 16 patients (5.6%). Major complications were surgical in 12 patients and medical in 4. Of the major surgical complications 3, 6, 1, 1 and 1 occurred during laparoscopic radical nephrectomy, donor nephrectomy, nephroureterectomy, simple nephrectomy and partial nephrectomy, respectively. The predominant major surgical complication was bleeding requiring conversion to an open surgical procedure. The overall conversion rate was 4% (12 patients), consisting of 6 emergency and 6 elective conversions. The remaining 27 patients experienced minor surgical or postoperative medical problems, such as urinary retention or wound infection. The mortality rate in our series was 0%. CONCLUSIONS: Laparoscopic renal surgery is becoming a routine procedure in the armamentarium of many urologists. Complications that are unique to laparoscopy exist but they should decrease with time with repetition and experience. We have learned many different precautions and procedures that should help decrease the risk of future complications associated with laparoscopic renal surgery.
Female↗
Intravesical therapy for superficial bladder cancer: slow but steady progress.
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Administration, Intravesical↗
Mayo Clinic Scottsdale experience with laparoscopic nephron sparing surgery for renal tumors.
PURPOSE: Nephron sparing surgery is an accepted treatment for small renal masses, of which many have been detected incidentally due to the widespread use of advanced imaging techniques. We report our experience with laparoscopic nephron sparing surgery. MATERIALS AND METHODS: From May 2000 to May 2002 a total of 20 laparoscopic partial nephrectomies were performed in 19 patients. The kidney was mobilized to allow adequate dissection, hemostasis and inspection of the kidney. Cautery, a harmonic scalpel and a TissueLink (TissueLink Medical, Inc., Dover, New Hampshire) device were variably used for dissection and hemostasis. Further hemostasis was then achieved using an argon beam laser with Fibrillar (Fibrillar Ethicon, Somerville, New Jersey), fibrin glue or the TissueLink device. Intact removal and biopsy of the lesion base were done to assess margin status. RESULTS: Mean patient age was 66 years (range 41 to 80). Mean tumor size was 2.1 cm. (range 1 to 7) and average operative time was 130 minutes (range 60 to 210). Mean hospital stay was 2.2 days. Mean estimated blood loss was 120 ml. (range 20 to 400) and no blood transfusions or conversions to an open procedure were required. Complications included intraoperative fragmentation of a tumor in 1 case, postoperative dyspnea, postoperative bleeding and pneumonia in 1. CONCLUSIONS: Laparoscopic partial nephrectomy for small renal tumors was performed safely and effectively. Technique depended on the size and location of the mass. Long-term followup is required to compare cancer control with that of open nephron sparing surgery.
Adult↗
Superficial bladder cancer.
Superficial bladder cancer can be resected with minimal morbidity, but the patients are at high risk for tumor recurrence. Tumors can be divided into low-, intermediate-, and high-risk categories based on tumor grade, stage, and pattern of recurrence. Low-risk tumors are best treated with a single instillation of chemotherapy such as thiotepa, doxorubicin, or mitomycin. Intermediate-risk tumors can be treated with chemotherapy, but, similar to high-risk tumors, will often require immunotherapy. High-risk tumors are best treated with intravesical bacille Calmette-Guérin (BCG) using a 3-week maintenance schedule. Side effects of BCG immunotherapy can be reduced by logarithmic reductions in the dosage of BCG. Patients who fail BCG may be rescued with BCG plus interferon-alfa or radical cystectomy.
Combined Modality Therapy↗
Intravesical bacillus Calmette-Guerin reduces the risk of progression in patients with superficial bladder cancer: a meta-analysis of the published results of randomized clinical trials.
PURPOSE: We determine if intravesical bacillus Calmette-Guerin (BCG) reduces the risk of progression after transurethral resection to stage T2 disease or higher in patients with superficial (stage Ta, T1 or carcinoma in situ) bladder cancer. MATERIALS AND METHODS: A meta-analysis was performed of the published results of randomized clinical trials comparing transurethral resection plus intravesical BCG to either resection alone or resection plus another treatment other than BCG. RESULTS: We identified 24 trials with progression information on 4,863 patients. Based on a median followup of 2.5 years and a maximum of 15 years, 260 of 2,658 patients on BCG (9.8%) had progression compared to 304 of 2,205 patients in the control groups (13.8%), a reduction of 27% in the odds of progression on BCG (OR 0.73, p = 0.001). The percent of patients with progression was low (6.4% of 2,880 patients with papillary tumors and 13.9% of 403 patients with carcinoma in situ, reflecting the short followup and relatively low risk patients entered in many of the trials. The size of the treatment effect was similar in patients with papillary tumors and in those with carcinoma in situ. However, only patients receiving maintenance BCG benefited. There was no statistically significant difference in treatment effect for either overall survival or death due to bladder cancer. CONCLUSIONS: Intravesical BCG significantly reduces the risk of progression after transurethral resection in patients with superficial bladder cancer who receive maintenance treatment. Thus, it is the agent of choice for patients with intermediate and high risk papillary tumors and those with carcinoma in situ.
Administration, Intravesical↗
Chemoprevention of bladder cancer.
The data presented herein, although highly supportive for a protective role of various nutrients against bladder cancer, are far from definitive. Many authorities question the validity of current recommendations for nutritional chemoprevention against bladder cancer. The reason for the wide variations reported in epidemiologic studies lies in the nature of observational studies. Dietary studies are limited in their conclusions because the protection afforded by the consumption of a particular nutrient may be multifactorial, with different components of the food exerting potential chemopreventive effects. Furthermore, measuring levels of nutrients in the food intake of populations is confounded by factors that might affect these levels and also the incidence of cancer. For example, vitamin A can come from animal or vegetarian sources. Because animal fat has been identified as a potential carcinogen in man, depending on the source of the vitamin, varying levels of protection might be deduced. In addition, chemoprevention studies using dietary supplements are expected to have mild effects, and large studies would be required to confirm statistical significance. Even with agents such as intravesical chemotherapy, only half the studies achieve statistical significance [29]. Prospective randomized trials with a large sample size, longer follow-up, and an extended duration of treatment are needed to clarify the association between micronutrients and cancer protection. With these caveats in mind, several recommendations can be made. Simple measures, such as drinking more fluids (especially water), can have a profound impact on the incidence of bladder cancer. Vitamins are being extensively studied in chemopreventive trials for different cancers. There is strong evidence for a chemoprotective effect of vitamin A in bladder cancer. The authors recommend 32,000 IU/day of vitamin A initially, with lower doses (24,000 IU) for persons less than 50 kg. Because liver toxicity is a possibility with long-term administration, the dose should be decreased to 16,000 IU after 3 years. High doses of beta-carotene should be avoided based on a large clinical trial reporting a 25% increase in the number of cases of prostate cancer and a statistically significant increase in the incidence of lung cancer. Vitamin B6 has been studied in several clinical trials in bladder cancer. The US-based Veterans Administration cooperative study found benefit for vitamin B6 when given as a single agent. Data for vitamins C and E are insufficient to recommend either agent as stand-alone treatment. Nonetheless, each of these vitamins is known to have beneficial effects, including improved function of the immune system. It is possible that only a small percentage of patients with bladder cancer respond to vitamins B6, C, or E, yet each is safe, nontoxic, and inexpensive. In an effort to pool the efficacy of individual agents and to increase the power of study, the authors evaluated the combination of vitamins A, B6, C, and E in a double-blind trial. The observed 50% 5-year reduction in tumor recurrence was highly significant and greater than would be expected for any of the individual ingredients and suggests that combinations of nutritional agents may be most appropriate. A large-volume study along similar lines is being conducted. Among the numerous other compounds and dietary substances purported to have chemopreventive effect, soybeans, garlic, and green tea stand out as having the greatest promise and can freely be recommended to patients. For synthetically synthesized agents such as celecoxib, piroxicam, or DFMO, recommendations must be deferred until the results of clinical trials are conclusively in favor of their use. Many of the dietary factors found to be protective against bladder cancer are being investigated in other cancers and are beneficial to general health. Although naturally occurring nutrients are ideal, especially because the delicate balance of various micronutrients might be impossible to synthesize in the laboratory, the general population finds it easier to take vitamin supplements. Unfortunately, dietary changes such as decreasing fat and increasing fruit and vegetable intake are more difficult to initiate. There is a mistaken notion that simply because an agent is naturally occurring, it cannot be as beneficial as taking a substance synthesized in the laboratory. Even in a high-risk group such as nuclear-bomb survivors in Japan, high consumption of vegetables and fruit is protective against bladder cancer [44]. Encouraging patients to follow an essentially healthy food habit lifestyle will be a significant contribution in the fight against cancer.
Anti-Inflammatory Agents, Non-Steroidal↗
Mayo Clinic Scottsdale Experience with laparoscopic nephroureterectomy.
OBJECTIVES: To evaluate the efficacy of laparoscopic nephroureterectomy for patients with transitional cell carcinoma of the upper urinary tract. METHODS: Eighteen patients underwent attempted transperitoneal laparoscopic nephroureterectomy between June 2000 and October 2002. Mean patient age was 67.5 years. The specimen was removed intact through a 7- to 9-cm extraction incision in the lower midline. In the majority of patients, the distal ureter was dissected through the extraction incision. RESULTS: Sixteen cases were completed laparoscopically. Two cases required conversion to an open procedure. In these cases, dense fibrosis was present around the renal hilum preventing further dissection. The mean operative time was 180 minutes, and the mean estimated blood loss was 160 mL. The mean length of stay was 3.3 days. Complications included the 2 conversions, and 1 patient with a postoperative Mallory Weiss tear. No port-site or distant metastasis occurred; however, 1 patient developed a retroperitoneal recurrence. CONCLUSION: Laparoscopic nephroureterectomy is an alternative to open nephroureterectomy. Cases with high-stage and grade may cause the laparoscopic dissection to be difficult. The extraction incision allows for easy dissection of the distal ureter.
Aged↗
Cisplatin, gemcitabine and paclitaxel triplet chemotherapy in 50 patients with advanced or metastatic urothelial cancer.
At West Virginia University in Morgantown, we conducted a phase 2 study to investigate 50-mg/m2 cisplatin, 1,000-mg/m2 gemcitabine, and 75-mg/m2 paclitaxel (CGP) "triplet" chemotherapy for advanced urothelial cancer. Fifty patients received CGP days 1 and 8 of a 3- to 4-week cycle. Transitional cell carcinoma alone occurred in 38 patients; 12 had mixed histologic findings (adenocarcinoma or squamous cell carcinoma). Thirty-one (M0) had advanced regional disease; 19 (M1) had metastases. NCI performance status was 0 to 2 in 33 patients and 3 to 4 in 17 patients. Grade 3 or 4 toxicity occurred in 33% of patients administered 218 chemotherapy cycles. Objective tumor responses occurred in 11 M1 patients (complete in 2) and in 17 M0 patients (complete in 11). Median survival was 13.5 (M1) and 16.8 (M0) months. Our study shows that CGP for urothelial cancer is effective and has manageable toxicity. Seventy percent of our patients were ineligible for standard clinical trials.
Adult↗