Regula Markwalder

Radical Cystectomy for Bladder Cancer Today—A Homogeneous Series Without Neoadjuvant Therapy

PURPOSE To investigate the effect of pelvic lymph node dissection and radical cystectomy for transitional cell cancer of the bladder on recurrence-free and overall survival, pelvic recurrences, and metastatic patterns in a homogeneous group. PATIENTS AND METHODS A consecutive series of patients undergoing pelvic lymphadenectomy and radical cystectomy between 1985 and 2000 was analyzed. All patients were staged N0, M0 preoperatively, and no patient received neoadjuvant radio/chemotherapy. Pathologic characteristics based on the 1997 tumor-node-metastasis system, recurrence-free/overall survival, and metastatic patterns were determined. RESULTS Five hundred seven patients (age 66 +/- 12 years) with a mean follow-up time of 45 months (range, 0.1 to 176 months) were analyzed. Five-year recurrence-free and overall survival were, respectively, 73% and 62% for patients with organ-confined, lymph node-negative tumors (n = 217; < or = pT2, pN0) and 56% and 49% for non-organ-confined, lymph node-negative tumors (n = 166; > pT2, pN0). Positive lymph nodes were found in 124 (24%) patients who had a 5-year recurrence-free (33%) or overall (26%) survival. Isolated local recurrences were observed in 3% of patients with organ-confined tumors (< or = pT2, pN0), 11% with non-organ-confined tumors (> pT2, pN0), and 13% with positive lymph nodes (any pT, pN+). Distant metastases developed in 25% of patients with organ-confined tumors, 37% with non-organ-confined tumors, and 51% with positive lymph nodes. CONCLUSION Despite negative preoperative staging, pelvic lymphadenectomy and cystectomy for bladder cancer reveal a high percentage of unsuspected nodal metastases (24%) that have a 25% chance for long-term survival. This procedure also ensures a low pelvic recurrence rate even in lymph node-positive patients, and patients with locally advanced cancer have a 56% probability of 5-year recurrence-free survival.

Is a Limited Lymph Node Dissection An Adequate Staging Procedure for Prostate Cancer

PURPOSE Generally lymph node dissection is only considered a staging procedure for prostate cancer. Therefore, the need for meticulous lymph node dissection is often questioned and only sampling is suggested. We performed a prospective study to identify the pattern of lymph node metastasis in prostate cancer and determine how extensive lymph node dissection must be not to under stage cases. MATERIALS AND METHODS All patients with clinically organ confined prostate cancer, no prior hormonal treatment, negative preoperative staging computerized tomography and bone scan, who underwent radical prostatectomy between 1989 and 1999, were evaluated prospectively as to the number and location of lymph node metastasis. A meticulous lymph node dissection was performed along the external iliac vein, obturator nerve and internal iliac (hypogastric) vessels. Nodes from each location and side were submitted separately for histological evaluation. RESULTS In 365 patients with a median serum prostate specific antigen of 11.9 ng./ml. (range 0.4 to 172) the median number of nodes removed was 21 (range 6 to 50). Lymph nodes were positive in 88 (24%) patients and the median number of positive nodes was 2 (range 1 to 19). Internal iliac lymph nodes were positive in 51 (58%) of the 88 patients, including 34 with additional positive lymph nodes along the external iliac vein and/or obturator nerve. Internal iliac lymph nodes alone were positive in 17 (19%) of 88 patients. CONCLUSIONS There were significant numbers of lymph node metastases at all 3 different areas of lymphadenectomy. Positive lymph nodes were found along the internal iliac artery in more than half (58%) of the patients and exclusively in 19%. Therefore, we consider lymph node dissection along the internal iliac (hypogastric) vessels essential for representative staging. Without this dissection a fifth of node positive cases would have been under staged and diseased nodes would have remained in more than half of the cases.

Pelvic lymph node metastases from bladder cancer: outcome in 83 patients after radical cystectomy and pelvic lymphadenectomy.

PURPOSE We evaluate the outcome in patients with node positive bladder cancer with particular reference to the effect of individual characteristics of positive nodes on survival after meticulous pelvic lymphadenectomy at cystectomy. MATERIALS AND METHODS This prospective analysis contains 452 cases of bladder cancer staged preoperatively as N0M0, managed with pelvic lymphadenectomy and cystectomy between 1984 and 1997. A total of 83 (18%) patients with histologically confirmed node positive disease are included in our study. RESULTS The median overall survival of patients with positive nodes was 20 months. Median 5-year survival was 29%. Patients who survived were found with positive nodes at each site in the pelvis. The median survival of 57 patients with less than 5 positive nodes was 27 months, compared with 15 months for 26 with 5 nodes or more (log-rank test p = 0.0027). Median survival of 26 patients with no lymph node capsule perforation was 93 months, compared with 16 months for 57 with capsule perforation (p = 0.0004). The median survival of 18 patients with a maximum diameter of lymph node metastasis up to 0.5 cm. was 64 months, compared with 16 months for 65 with nodal metastasis greater than 0.5 cm. (p = 0.024). Contralateral positive nodes were found in 16 of 39 (41%) patients with unilateral bladder cancer. CONCLUSIONS Long-term survival is possible with node positive bladder cancer. Those patients with few as well as smaller and, therefore, unsuspected nodal metastases, and those without lymph node capsule perforation have the best results after removal of pelvic metastatic nodal disease. Because patients who survive may be found regardless of the site of pelvic nodal metastases, meticulous bilateral pelvic lymphadenectomy is warranted in all patients at the time of attempted curative cystectomy for bladder cancer, particularly if there is no clinical evidence of nodal involvement.

Extracapsular Extension of Pelvic Lymph Node Metastases From Urothelial Carcinoma of the Bladder Is an Independent Prognostic Factor

Purpose To analyze the prognostic impact of risk factors for urothelial carcinoma of the bladder (UCB) with pelvic lymph node (LN) metastases. Patients and Methods We analyzed a consecutive series of 507 patients with UCB who were preoperatively staged N0M0. One hundred one of 124 eligible patients who were treated with radical cystectomy and standardized extended bilateral pelvic lymphadenectomy with curative intent and had postoperatively confirmed LN metastases were evaluated in regard to recurrence-free and overall survival. Results A median of 22 nodes per patient (range, 10 to 43 nodes) were removed and examined. Median recurrence-free and overall survival durations were 17 months and 21 months (range for both, 1 to 191 months), respectively. In the multivariate analysis for recurrence-free survival, extracapsular extension of LN metastases was the strongest prognostic factor (P = .019). Other variables such as tumor stage (pT1/2 v pT3 and pT4), the number (< five v ≥ five), and the percentage (< 20...

Long-term experience with bacillus Calmette-Guerin therapy of upper urinary tract transitional cell carcinoma in patients not eligible for surgery.

PURPOSE Carcinoma in situ and urothelial tumors of the upper urinary tract become problematic in cases of bilateral occurrence or solitary kidney. Perfusions with bacillus Calmette-Guerin (BCG) have been reported beneficial, however, only long-term results will determine the validity of this treatment. MATERIALS AND METHODS We retrospectively evaluated the results of BCG therapy for upper urinary tract disease in 37 patients. All 37 patients had undergone previous surgical treatment for urothelial cancer, had a positive cytology or biopsy for upper urinary tract cancer and were ineligible for radical nephroureterectomy with a bladder cuff. After placement of a 10Fr nephrostomy tube with the patient under local anesthesia 6 weekly perfusions of BCG were administered after radiological documentation of unhindered flow from the renal pelvis to the bladder or urinary diversion. A total of 25 renal units were treated with curative intent for carcinoma in situ and 16 renal units were treated for Ta or higher urothelial tumors in an adjuvant setting after endoscopic resection. RESULTS In 37 patients 41 renal units were treated with BCG perfusions and were followed for a median of 42 months (range 8 to 137). In 1 patient BCG inflammation and in 2 others severe septicemia developed after the first perfusion. There was no tumor seeding along the nephrostomy tract in any patient. BCG perfusion therapy did not alter renal function. Overall median survival was 42 months (range 1 to 137), median recurrence-free survival was 21 months (1 to 137) and progression-free survival was 34 months (1 to 118). Of the 37 patients 14 (38%) died of urothelial cancer, 11 of other causes (29%) and 12 (33%) are alive. CONCLUSIONS BCG perfusion therapy of the upper urinary tract for papillary tumors or carcinoma in situ is a valid treatment option with acceptable side effects for patients not amenable to conventional radical surgical therapy. BCG therapy of upper urinary tract urothelial tumors may prevent patients from requiring dialysis and provides cure in those with carcinoma in situ of the upper urinary tract. In this negatively selected patient population BCG buys time for some but does not provide cure except for carcinoma in situ.

Estrogen and progesterone receptors in meningiomas in relation to clinical and pathologic features

Tumor estradiol and progesterone binding sites were studied in 34 patients with meningioma. Twenty of the meningiomas contained very low titers (mean, 45 fmol/g of tumor; range, 0-201 fmol/g of tumor) of a nonspecific cytoplasmic [3H]estradiol binding component, whereas 26 of the tumors contained high titers of specific high-affinity cytosol [3H]promegestone (R5020; progesterone) binding sites (mean, 1476 fmol/g of tumor; range, 0-8328 fmol/g of tumor). No nuclear binding activity for [3H]estradiol could be detected in 12 of the 34 meningiomas studied, irrespective of the progesterone binding activity. There was no correlation between high progesterone binding activity and the age or the sex of the patient, nor between tumor location and cellular mitotic index. However, progesterone binding activity was present more frequently in meningothelial (95%, 18/21 patients) than in transitional (55%, 5/9 patients) or fibroplastic (25%, 1/4 patients) tumor histologic types. These data suggest that the cellular biosynthesis of the progesterone binding component in meningiomas is not estrogen regulated as it is in other classic estrogen target tissues, such as the breast.

Prognostic implications of extracapsular extension of pelvic lymph node metastases in urothelial carcinoma of the bladder.

To determine whether extracapsular extension of pelvic lymph node metastases from urothelial carcinoma of the bladder is of prognostic significance. From a consecutive series of 507 patients with urothelial carcinoma of the bladder preoperatively staged N0M0, 101 of 124 patients with lymph node metastases detected on histologic examination fulfilled the inclusion criteria for this study and were evaluated. All underwent radical cystectomy between 1985 and 2000 with standardized extended bilateral pelvic lymphadenectomy in curative intent and were prospectively followed for recurrence-free (RFS) and overall (OS) survival. Staging was done according to UICC 2002. A total of 2375 lymph nodes were examined. The median number of nodes examined per patient was 22 (range, 10-43). The median number of positive nodes was 2 (range, 1-24). Median RFS and OS were 17 and 21 months (range for both, 1-191), respectively. The 5-year RFS and OS rates were 32% and 30%, respectively. There were 59 patients (58%) with extracapsular extension of lymph node metastases. They had a significantly decreased RFS (median, 12 vs. 60 months, P = 0.0003) and OS (median, 16 vs. 60 months, P < 0.0001) compared with those with intranodal metastases. There were no significant differences in survival between pN1 and pN2 categories with extracapsular extension of the lymph node metastases (RFS, P = 0.70; OS, P = 0.65) or those without extension (RFS, P = 0.47; OS, P = 0.34). On a multivariate analysis, extracapsular extension of lymph node metastases was the strongest negative predictor for RFS. Meticulous lymph node resection and subsequent thorough histologic examination in patients undergoing radical cystectomy for bladder cancer reveals a high incidence of lymph node-positive disease (24%) despite negative preoperative staging. Lymph node metastases with extracapsular extension in pN1 and pN2 stages carry a very poor prognosis. Therefore, this feature should be used to designate a separate pN category in the staging system. The discrimination of pN1/pN2 in the UICC 2002 classification seems to be arbitrary and of no significant prognostic relevance.

Estrogen and progestin receptors in meningiomas: clinicopathological correlations.

Estradiol and progesterone receptors were studied in 44 patients with meningiomas and correlated to the clinicopathological features and amount of preoperative corticosteroid therapy. Thirty-four (77%) of the meningiomas contained high tilers of specific high-affinity cytosol [3H]promegestone (R 5020) binding sites (mean 2,902 fmol/g tumor; range 0–9,598 fmol/g tumor) whereas only minuscule amounts of a nonspecific cytoplasmic [3H]estradiol binding component (mean 48 fmol/g tumor; range 0–201 fmol/g tumor) were detectable. No nuclear binding activity for [3H]estradiol was demonstrable. There was no convincing correlation between high PR activity and the age, sex, or menopausal status of the patients. The correlation study between the amount of preoperative corticosteroid therapy with the amount of [3H]promegestone binding revealed no dose relationship. Correlating [3H]promegestone content with the histologic type, we found 96% of meningothelial, 71% of transitional, and 40% of fibroplastic; meningiomas to contain progesterone receptors. The necessity of in vitro studies is stressed to assess the biosynthesis and biological activity of the progesterone receptor in meningiomas, which is apparently not estrogen regulated, as is the case in other estrogen target tissues.

Prognostic factors in lymph node metastases of prostatic cancer patients: the size of the metastases but not extranodal extension independently predicts survival

Aims:  To analyse tumour characteristics and the prognostic significance of prostatic cancers with extranodal extension of lymph node metastases (ENE) in 102 node‐positive, hormone treatment‐naive patients undergoing radical prostatectomy and extended lymphadenectomy.

Biological expression of steroid hormone receptors in primary meningioma cells in monolayer culture.

Primary meningiomas have been grown in monolayer culture and tested for the presence of steroid hormone receptors and sensitivity to various steroids and steroid antagonists. None of the 10 solid tumors or the primary cultures derived from them contained estrogen receptors, either in the cytoplasm or in the nucleus. Progesterone receptors were present in 50–70% of the solid tumors and some of the primary cultures. Four of four and five of five primary cultures contained, respectively, androgen and glucocorticoid receptors. When one of the primary cultures was tested for growth sensitivity to estrogen, tamoxifen, progesterone, hydrocortisone, and dihydrotestosterone, the last two had noticeable stimulatory effects on growth by day 5. Interestingly, only androgen and glucocorticoid receptors were present in the primary tumor cells in culture, suggesting that these receptors mediated the effects of their respective hormones on growth.