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S Groshen

Publications and source records attributed to S Groshen.

At least 73 records · Page 4Linked to original sources
PubMed1997

Variations in treatment of rectal cancer: the influence of hospital type and caseload.

PURPOSE: Surgical options for the treatment of rectal cancer may involve sphincter-sparing procedures (SSP) or abdominoperineal resection (APR). We sought to examine variations in the surgical treatment of rectal cancer for a large, well-defined patient population and specifically to determine if differences exist in management and survival based on hospital type and surgical caseload. METHODS: The Cancer Surveillance Program database for Los Angeles County was used to retrospectively retrieve data on all patients who underwent SSP or APR for rectal adenocarcinoma between 1988 and 1992. RESULTS: A total of 2,006 patients with adenocarcinoma of the rectum underwent SSP or APR during the study period. Overall, 55 percent underwent SSP, and the remaining 45 percent underwent APR. Use of SSP remained relatively constant for each year of the five-year period. Substantial variability was seen in the use of SSP at various hospital types. For localized disease, this varied from as low as 52 percent at teaching hospitals to as high as 78 percent at hospitals approved by the American College of Surgeons (P = 0.067). To examine the role of caseload experience, hospitals were divided into those completing an average of five or fewer rectal cancer cases per year vs. those completing an average of more than five cases per year. For localized disease, hospitals with higher caseloads performed SSP in significantly more cases, 69 vs. 63 percent (P = 0.049). Survival was seen to be significantly improved for patients operated on at hospitals with higher caseloads, in cases of both localized and regional diseases (P < 0.001). CONCLUSION: Surgical choices in the treatment of rectal cancer may vary widely, even in a well-defined geographic region. Although the reasons for this variability are multifactorial, hospital environment and surgical caseload experience seem to have a significant role in the choice of surgical procedure and on survival.

Adenocarcinoma↗
PubMed1997

Pelvic examination, tumor marker level, and gray-scale and Doppler sonography in the prediction of pelvic cancer.

OBJECTIVE: To determine the ability of pelvic examination, tumor marker assessment, and transvaginal ultrasonography, with selected use of Doppler ultrasonography, to predict pelvic malignancy. METHODS: Two hundred twenty-six women scheduled for operative removal of a pelvic mass were entered in the study prospectively. Each woman underwent pelvic examination, tumor marker assessment, and transvaginal ultrasonography preoperatively. Women whose gray-scale findings were suspicious for malignancy underwent Doppler ultrasonography. Suspicious findings included masses that were fixed or irregular on pelvic examination; CA 125 level greater than 35 U/mL; elevations in serum lactic dehydrogenase, alpha-fetoprotein, or hCG; and the presence of a substantial solid component on gray-scale ultrasonography. Suspicious Doppler findings included intratumoral color flow, pulsatility index less than 1.0, or resistance index 0.4 or lower. The findings were correlated with the presence of malignancy. RESULTS: If all three indicators (examination, tumor marker assessment, and gray-scale ultrasound findings) were nonsuspicious, 99% of premenopausal women and 100% of postmenopausal women had benign masses. If all three indicators were suspicious, 77% of premenopausal women and 83% of postmenopausal women had malignant tumors. Logistic regression identified ultrasound impression and tumor size to be significant predictors of malignancy in premenopausal women, whereas CA 125 level and ultrasound impression were significant in postmenopausal women. In patients with suspicious gray-scale findings, recategorization based on Doppler findings resulted in inferior diagnostic indices. CONCLUSIONS: Ultrasonographic tumor size and appearance are the best predictors of pelvic malignancy in premenopausal women, whereas CA 125 level and ultrasonographic appearance are the best predictors in postmenopausal women. Neither color nor spectral Doppler is useful in this setting.

Biomarkers, Tumor↗
PubMed1997

Fifteen-year survival and recurrence rates after radiotherapy for localized prostate cancer.

PURPOSE: To determine 15-year survival and recurrence rates after radiotherapy for localized prostate cancer. METHODS: One hundred thirty-six patients with clinically localized prostate cancer treated from 1966 to 1974 with interstitial gold seed and external-beam irradiation were evaluated to determine the probability of recurrence and survival > or = 15 years after therapy. All patients were surgically staged with pelvic lymphadenectomy and none received hormonal therapy before relapse. RESULTS: Overall, 60 patients (44%) have never recurred, although 57% (34 of 60) of these same patients have died of causes other than prostate cancer. Local progression developed in 39% of patients and distant metastases in 42%. At 15 years, the probability of dying of prostate cancer was 33%+/-8% (% +/- 2SE) and of all causes was 72%+/-8%. In clinical stage A2 and B, 29%+/-9% of patients died of their cancer within 15 years, compared with 57%+/-21% in stage C1, while only 18%+/-8% with clinical stage A2 and B and negative lymph nodes died of cancer within this period. In contrast, the prostate cancer mortality rate at 15 years was high for patients with positive nodes regardless of the stage of the primary tumor (73% for A2 and B; 71% for C1). Patients with nodal metastases, poorly differentiated tumors, and advanced local disease all had a significantly (P < .0001) increased risk of cancer death. CONCLUSION: The cancer-specific mortality rate for patients with stage A2 and B tumors and negative nodes compares favorably with other series of patients treated with radiation therapy and > or = 15 years' follow-up evaluation. While local progression rates are high and associated with a substantial risk of prostate cancer death, many patients live with the disease and ultimately die of causes other than prostate cancer.

Adult↗
PubMed1997

Quantitation of intratumoral thymidylate synthase expression predicts for disseminated colorectal cancer response and resistance to protracted-infusion fluorouracil and weekly leucovorin.

PURPOSE: Response rates to fluorouracil (5-FU)-based therapy remain low. As new, active agents are being tested, information regarding specific intratumoral genetic determinants of chemotherapy sensitivity or resistance can be used to plan therapy rationally. Intratumoral thymidylate synthase (TS) quantitation may be among the most important determinants of sensitivity or resistance to 5-FU. MATERIALS AND METHODS: Forty-six disseminated colorectal cancer patients had measurable tumor biopsies for polymerase chain reaction (PCR)-based determination of TS mRNA pretreatment. Protracted infusion of 5-FU 200 mg/m2/d for 21 days with weekly intravenous leucovorin 20 mg/m2 each cycle was given. After two cycles, responses were evaluated. Response data were correlated with independently determined intratumoral ratios of TS/beta-actin mRNA for each patient. RESULTS: TS/beta-actin ratios were successfully obtained for 42 patients (91%). TS/beta-actin ratios ranged from 0.3 x 10(-3) to 18.2 x 10(-3) (median, 3.5 x 10[-3]). Twelve patients (26%) responded to treatment (median TS/beta-actin ratio, 1.7 x 10[+3]). Thirty-four patients did not respond (median TS/beta-actin ratio, 5.6 x 10[-3]). No patient with a TS mRNA level greater than 4.1 x 10(-3) responded. The median TS/beta-actin ratio (3.5 x 10[-3]) significantly segregated responders from nonresponders (P = .001). Median survival for patients with TS/beta-actin ratios < or = 3.5 x 10(-3) was 13.6 months; for patients with TS/beta-actin ratios greater than 3.5 x 10(-3), it was 8.2 months (P = .02). CONCLUSION: For this cohort, the intratumoral TS/beta-actin ratio had a statistically significant association with response and survival. This relationship for other 5-FU schedules remains unknown. Confirmation of these data in a larger patient population could lead to determination of therapy for disseminated colorectal cancer based on a specific intratumoral molecular parameter.

Actins↗
PubMed1997

Phase II study of liposomal doxorubicin in refractory ovarian cancer: antitumor activity and toxicity modification by liposomal encapsulation.

PURPOSE: A phase II study of liposomal doxorubicin was conducted in patients with ovarian cancer who failed to respond to platinum- and paclitaxel-based regimens. Liposomal doxorubicin was selected as a result of its superior activity against ovarian cancer xenografts relative to free doxorubicin and activity in refractory ovarian cancer patients that was noted during the phase I study. PATIENTS AND METHODS: Thirty-five consecutive patients were accrued in two institutions (22 in one and 13 in the other). All had progressive disease after either cisplatin or carboplatin and paclitaxel, or at least one platinum-based and one paclitaxel-based regimen. Patients received intravenous (I.V.) liposomal doxorubicin 50 mg/m2 every 3 weeks with a dose reduction to 40 mg/m2 in the event of grade 3 or 4 toxicities, or a lengthening of the interval to 4 weeks (and occasionally to 5 weeks) with persistence of grade 1 or 2 toxicities beyond 3 weeks. RESULTS: Nine clinical responses (one complete response [CR], eight partial responses [PRs]) were observed in 35 patients (25.7%), with seven of these having been confirmed by two consecutive computed tomographic (CT) measurements. The median progression-free survival was 5.7 months with an overall survival of 1.5 to 24+ months (median, 11 months). Although 13 patients experienced grade 3 or 4 nonhematologic skin and mucosal toxicities (either hand-foot syndrome or stomatitis), with dose modifications, the treatment was very well tolerated. Nausea that was clearly attributable to the drug, hair loss, extravasation necrosis, or decreases in ejection fraction did not occur. CONCLUSION: Liposomal doxorubicin has substantial activity against ovarian cancer refractory to platinum and paclitaxel. The responses achieved with liposomal doxorubicin were durable and maintained with minimal toxicity. This liposomal formulation should be evaluated further in combination with other drugs in less refractory patients.

Aged↗
PubMed1997

Active specific immunotherapy of metastatic melanoma with an antiidiotype vaccine: a phase I/II trial of I-Mel-2 plus SAF-m.

PURPOSE: To determine the toxicity and immunologic activity of an antiidiotype melanoma vaccine that consists of monoclonal antibody I-Mel-2 (MELIMMUNE-2, IDEC Pharmaceuticals, La Jolla, CA) and an immunologic adjuvant SAF-m. PATIENTS AND METHODS: Twenty-six patients with metastatic melanoma, 17 of whom had previously received chemotherapy, were given 2 mg of I-Mel-2 and either 100 micrograms (n = 6) or 250 micrograms (n = 20) of SAF-m. Antiidiotype vaccine was given intramuscularly (IM) biweekly for 4 weeks, and then bimonthly until disease progression. Human antimurine antibodies (HAMA), anti-I-Mel-2 antibodies, and specific antibody (Ab)3 against the melanoma epitope mimicked by the vaccine were titrated before treatment, biweekly from weeks 4 to 12, and every 4 to 8 weeks thereafter. Computed tomographic (CT) scans of the chest, abdomen, and pelvis and magnetic resonance imaging (MRI) of the brain were obtained before and bimonthly during treatment to evaluate responses. RESULTS: Elevated titers of human antimouse antibodies and anti-I-Mel-2 antibodies were associated with clinical antitumor effect (P = .02 and P = .05, respectively). Ab3 was absent in most patients, but was found in the best clinical responder. Fever, myalgias/arthralgias, fatigue, nausea, and headaches were the most common toxicities. Grade III myalgias/arthralgias and headaches required dose reduction of SAF-m in eight patients at the 250-microgram dose. No treatment-related death occurred. Six patients had an antitumor effect: one complete response in liver and lung, two minor responses, and three stable disease. The patient with a complete response has survived nearly 5 years. CONCLUSION: I-Mel-2 antiidiotype vaccine was safe, tolerated best at the 100-microgram dose of SAF-m, and had immunologic and clinical activity.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1997

WAF1/Cip1 gene polymorphism and expression in carcinomas of the breast, ovary, and endometrium.

The p53 gene is altered in approximately 50% of human cancers and is considered to be important in the pathogenesis of these malignancies. The p53 protein product regulates the transition from G1 to S phase of the cell cycle and entry to the DNA damage repair pathway. As alterations in this pathway appear to be important in a variety of human cancers, downstream effector proteins of p53 are potential sites for somatic alterations. WAF1/Cip1, also known as WAF1, Cip1, sdi1, or CAP20, codes for a 21-kd protein (p21WAF1/Cip1), which was recently described as a universal inhibitor of cyclins and is thus critical in cell cycle control. Mutations in WAF1/Cip1 are potentially important in human malignancies because they could affect the control of the cell cycle. To understand whether mutations of WAF1/Cip1 occur in cancer, we screened 53 cases of invasive breast carcinoma, 35 cases of ductal carcinoma in situ (DCIS), 53 ovarian carcinomas, and 47 endometrial carcinomas in the second exon of WAF1/Cip1 (90% of the open reading frame). p21WAF1/Cip1 expression was characterized with immunohistochemistry. Cells from the blood of 21 normal individuals were also characterized using single-strand conformational polymorphism analysis, DNA sequencing and restriction analysis. Single-strand conformational polymorphism analysis demonstrated an altered mobility pattern for exon 2 in 12 invasive breast cancers (22.6%), 5 DCIS of the breast (14%), 8 invasive ovarian carcinomas (15%), and 9 endometrial carcinomas (19%). In total, 209 samples were screened, and 38 cases (18.2%) had an altered codon 31. Each case with altered single-strand conformational polymorphism, analyzed by DNA sequencing and/or restriction analysis, showed the same alteration of codon 31, a C to A transversion encoding a change in amino acid sequence from serine to arginine (31Ser-->31Arg). DNA from the blood of 21 normal individuals showed the same alteration in WAF1/Cip1 in 4 cases (19%). Furthermore, paired normal tissue was available for 3 of 20 breast carcinomas with the Ser31Arg transversion. Normal DNA from all 3 cases showed the same 31Arg alteration as found in the tumor tissue. These results indicate that codon 31 is a polymorphic site and that the serine to arginine shift is a polymorphism. p21WAF1/Cip1 expression, identified by immunohistochemistry, was found to vary in a pattern that depended both on the tissue type and on the presence or absence of the codon 31 polymorphism. Using pair-wise comparisons in breast DCIS, we found higher protein expression in tumor nuclei as compared with benign stromal cell nuclei (P = 0.002) or normal ductal epithelium (P = 0.005). Invasive breast cancer specimens showed a trend in p21WAF1/Cip1 immunostaining similar to DCIS but did not reach statistical significance (P = 0.12). However, when cases with extensive desmoplastic reaction were excluded, a statistically significant association (P = 0.019) similar to that in DCIS was noted. In contrast to the breast tumors, ovarian carcinomas exhibited significantly greater p21WAF1/Cip1 expression in the benign stromal (fibroblast) nuclei surrounding the tumor than in the carcinoma cell nuclei (P = 0.016). Endometrial carcinoma revealed no difference in staining when comparing benign tissue with carcinoma (P = 0.99); however, unlike breast and ovarian carcinomas in which there was no correlation between p21WAF1/Cip1 expression and the presence or absence of the alteration at the 31st codon, endometrial carcinomas showed an increased percentage of immunopositive nuclei associated (P = 0.056) with 31Arg. These results demonstrate tissue-specific expression patterns of WAF1/Cip1 in different tumors which appears to be characteristic of the tumor type.

Breast Neoplasms↗
PubMed1997

Relationship of tumor angiogenesis and nuclear p53 accumulation in invasive bladder cancer.

The purpose of this investigation was to evaluate the relationship between tumor angiogenesis and nuclear p53 accumulation in invasive bladder cancer. We studied 161 patients with invasive transitional cell carcinoma of the bladder who had previously undergone radical cystectomy. Analysis was performed to determine the presence of p53 nuclear accumulation and extent of tumor-associated angiogenesis. p53 status identified a group of patients at high risk for tumor progression (p53-altered tumors), and microvessel density determinations added additional prognostic information by identifying a subset of aggressive tumors within the wild-type p53 subgroup. At 5 years, patients with tumors exhibiting no evidence of p53 alterations and low microvessel counts demonstrated 3% recurrence and 88% survival, compared to 43% recurrence and 59% overall survival for patients with intermediate vessel counts and 61% recurrence and 43% overall survival for patients with the highest vessel counts (P < 0.001 and P = 0.003, respectively). Angiogenesis also provides additional prognostic information to patients with tumors that demonstrate p53 alterations. An association between angiogenesis and p53 status did exist (P = 0. 05); however, 27% of the tumors that showed no evidence of p53 alterations exhibited high microvessel counts, and 26% of tumors with evidence of p53 alterations had low microvessel counts. Tumor-associated angiogenesis adds additional useful prognostic information to that which is obtained from p53 status in patients with invasive transitional cell carcinoma of the bladder. Although an association between p53 status and the degree of angiogenesis was identified, other factors appear to play a role in the regulation of tumor-induced neovasularization.

Biomarkers, Tumor↗
PubMed1996

Initial studies on active immunization of HIV-infected subjects using a gp120-depleted HIV-1 Immunogen: long-term follow-up.

In 1987, exploratory clinical studies were initiated to determine whether the development of AIDS in HIV-infected individuals might be delayed or prevented by immunization with an inactivated HIV preparation. Preclinical studies had shown the preparation to be safe and immunogenic. Twenty-three patients with biopsy-confirmed persistent generalized lymphadenopathy (CDC III) and two with asymptomatic HIV infection and CD4 lymphocyte counts between 135 and 769/mm3 were studied, of whom eight (32%) had additional HIV-related symptoms. Over a 3-year period, they received a median of eight open-label inoculations of 100 micrograms of inactivated gp 120-depleted HIV-1 Immunogen in incomplete Freund's adjuvant (IFA). Clinical, general laboratory, immunologic, and virologic parameters were followed for up to 6 years. No serious treatment-related adverse experiences were reported, nor was accelerated HIV disease progression seen. Twelve patients developed a delayed-type hypersensitivity response (HIV-DTH) to the immunogen and nine showed fourfold or greater increases in anti-p24 antibody titers. In the follow-up period, 10 of the 25 patients developed AIDS and one with Kaposi's sarcoma (KS) at baseline progressed. Of the 12 patients who became HIV-DTH-responsive, one developed an opportunistic infection (OI), occurring approximately 5 years from study onset, and subsequently died. One additional HIV-DTH responder developed KS. Of the 13 patients who remained HIV-DTH-nonresponsive, nine (69%) progressed to AIDS and seven of these have died. Differences were also observed in terms of HIV-DNA copy number, CD4 percentages, and anti-p24 antibody patterns between the HIV-DTH-responsive and -nonresponsive groups, suggesting a more favorable clinical course in the former. HIV-1 Immunogen in IFA appears to be safe and immunogenic. Further studies are indicated to determine clinical efficacy of the HIV Immunogen as well as the significance of the apparent correlation between HIV-DTH responsivity and a more favorable clinical course.

AIDS Vaccines↗
PubMed1996

Comparison of conditional quality of life terminology and visual analogue scale measurements.

Two common formats for grading quality of life parameters are descriptive choices (mild, moderate, severe) and visual analogue scales. However the quantitative relationship between descriptive terminology and visual analogue scale scores has not been determined. A content neutral questionnaire was administered to 213 evaluable subjects who were asked to place the descriptors 'mildly', 'moderately', and 'severely' (presented in random order) on 100mm visual analogue scales. Visual analogue scales were presented without and then with hashmarks at 25mm, 50mm, and 75mm. Median visual analogue scale values for the descriptive terms differed significantly without hashmarks ('mildly' = 24mm', moderately' = 43mm, 'severely' = 84mm; p < 0.001) and also with hashmarks ('mildly' = 31mm, 'moderately' = 49mm, 'severely' = 85mm; p < 0.001). Comparison of interquartile range values (25th-75th percentile) revealed a distinct meaning for 'severely' (68-93mm) but marked overlap between 'mildly' (10-45mm) and 'moderately' (22-53mm). Errors of order (order other than 'mildly' < 'moderately' < 'severely') were made by 91 subjects. The discrepancy 'moderately' < 'mildly' accounted for most of these errors (72 subjects). Median values for 'mildly', 'moderately', and 'severely' are distinct and approximately linear on a visual analogue scale for large populations. However there is significant confusion between the terms 'mildly' and 'moderately' for individual subjects. Visual analogue scales can reveal finer quantitative differences than descriptive terms but require a significant time commitment for instruction and administration. Descriptive terms on a word-graphic scale or descriptive terms with numerical values to reenforce order of severity (0 = absent, 1 = 'mildly', 2 = 'moderately', 3 = 'severely') may be reasonable alternatives.

Adolescent↗
PubMed1996

H-2Ld-alloreactive T cell hybridomas utilize diverse V alpha and V beta T cell receptor chains.

We have sequenced the TCRs from Ld-specific alloreactive T cell hybridomas, whose reactivities we have found to be quite representative of those of a primary dm2 anti-BALB/cJ mixed lymphocyte reaction. We find V beta 6, V beta 7, V beta 8 and V beta 10 gene segments. V alpha usage is diverse, although closely related to that from peptide-specific Ld-restricted CTLs. V alpha-V beta selection provides evidence of preferential pairing. Amino acid frequency analysis shows that the alpha CDR2 region is rich in charged amino acids, in contrast to the beta CDR2 region. Our data suggests the beta chain may be more immunoglobulin-like than the alpha chain, and that charge complementarity may be important in TCR-MHC interactions. We do not consider our results to be contradictory to those previously reported but rather they may represent an early, more diverse response.

Amino Acid Sequence↗
PubMed1996

Thymidylate synthase mRNA level in adenocarcinoma of the stomach: a predictor for primary tumor response and overall survival.

PURPOSE: We tested the hypothesis that polymerase chain reaction (PCR) quantitation of the enzyme thymidylate synthase (TS) within a primary adenocarcinoma of the stomach, has an inverse relationship to response and survival for patients who receive fluorouracil (5FU)-based chemotherapy. PATIENTS AND METHODS: Before systemic chemotherapy, the genetic expression of TS (TSmRNA level) was determined using a PCR method. Gene expression was calculated by determining the ratio between the amount of radiolabeled PCR product with the linear amplification range of the TS gene and the beta-actin gene. Chemotherapy consisted of two cycles of protracted infusion (PI) 5FU 200 mg/m2/d administered for 3 weeks with leucovorin 20 mg/m2/w. Cisplatin 100 mg/m2 was administered on day 1. RESULTS: Sixty-five patients with primary gastric cancer had a median TS mRNA level of 4.6 x 10(-3) (range, 0.9 to 20.1 x 10(-3)). Thirty-five percent of patients had measurable responses in their primary tumors. The mean gastric cancer TSmRNA level in responding and resistant patients is statistically significant (P < .001). The median survival time was 43+ months for treated patients with TSmRNA levels less than the median and 6 months for those with TS m-RNA levels greater than the median (P = .003). CONCLUSION: The genetic expression of TS (TSmRNA level) influences response to 5FU-based chemotherapy and survival for a cohort of patients with primary gastric cancer. Confirmation of these data could lead to therapeutic decisions based on specific molecular properties within a tumor.

Adenocarcinoma↗
PubMed1996

Impact of moderate dose of postoperative radiation on urinary continence and potency in patients with prostate cancer treated with nerve sparing prostatectomy.

PURPOSE: We analyzed the impact on potency and urinary continence of moderate doses of radiation (45 to 54 Gy.) given postoperatively after nerve sparing prostatectomy. MATERIALS AND METHODS: Between 1983 and 1992, 294 of 762 prostate cancer patients were selected to undergo nerve sparing prostatectomy. Subjective patient reports regarding potency and urinary continence status were obtained preoperatively, 1 year postoperatively or 1 year after completion of radiation. RESULTS: Of the 294 patients 105 received postoperative radiotherapy (45 to 54 Gy.) to the prostatic bed. There were patients with more advanced stages of disease in the irradiated group, including 89% with stages C and D1 (pT3N0 and pT1 to 3, N1 to 3), compared to 14% with stages C and D1 (pT3N0 and pT1 to 3, N1 to 3) in the nonirradiated group (p < 0.001). No difference in urinary continence was noted in the irradiated (94%) compared to the nonirradiated group (92%, p = 0.64). Of the patients who underwent bilateral nerve sparing prostatectomy 44% who received and 48% who did not receive radiation had recovered potency at 1 year (p = 0.76). Of those who underwent unilateral nerve sparing prostatectomy 10% who received and 33% who did not receive radiation had recovered potency at 1 year (p = 0.14). Using multivariate analysis patient age younger than 63 years and bilateral versus unilateral nerve sparing procedures were significant predictors of potency. CONCLUSIONS: Our retrospective study suggests that at 1 year after treatment moderate doses of postoperative radiotherapy did not have a significant impact on the recovery of urinary continence and potency after nerve sparing prostatectomy. However, longer followup is required to determine the impact of this radiation protocol on long-term preservation of potency after nerve sparing prostatectomy.

Combined Modality Therapy↗
PubMed1996

Transitional cell carcinoma involving the prostate with a proposed staging classification for stromal invasion.

PURPOSE: We investigated the effect on survival of transitional cell carcinoma of the prostatic urethra, ducts and stroma, and determined the difference between prostatic stromal involvement occurring via direct extension through the bladder wall versus stromal invasion arising intraurethrally. MATERIALS AND METHODS: Between August 1971 and December 1989, 489 men underwent radical cystoprostatectomy for transitional cell carcinoma, including 143 (29.2%) identified with prostate involvement by transitional cell carcinoma, in the cystectomy specimen. Patients were separated into 2 groups: 1-19 in whom the primary bladder tumor extended full thickness through the bladder wall to invade the prostate (classified as P4a) and 2-124 in whom prostate involvement arose from within the prostatic urethra. RESULTS: Five-year recurrence-free and overall survival rates were 25 and 21%, respectively, in group 1 versus 64 and 55%, respectively, in group 2. In the 124 patients in group 2 survival rates were similar for those with prostatic urethral tumors or carcinoma in situ and ductal tumors (no stromal invasion). Five-year overall survival rates without and with stromal invasion were 71 and 36%, respectively (p < 0.0001). Transitional cell carcinoma of the prostatic urethra or ducts does not alter survival predicted by primary bladder stage alone. Prostatic stromal invasion arising intraurethrally significantly decreases survival, which varies based on primary bladder stage (64.6% in stage P1, 30.8% in stages P2/P3a and 13.6% in stage P3b, p = 0.0001). P1 bladder tumors with prostatic stromal invasion arising intraurethrally had a significantly higher survival rate than P4a tumors (64.6 versus 21%, p = 0.0001). P3b bladder tumors with stromal invasion had a survival rate similar to that of P4a tumors (p = 0.78). CONCLUSIONS: Prostatic urethral or ductal transitional cell carcinoma does not alter survival determined by primary bladder stage alone and it should not be classified as P4a. Prostatic stromal involvement arising intraurethrally significantly decreases survival predicted by primary bladder stage alone. P1 bladder tumors with prostatic stromal invasion arising intraurethrally have a significantly higher survival rate than P4a tumors and they should be separately classified as P1str. Muscle invasive (P2/P3a) bladder tumors with stromal invasion have a higher survival rate than P4a tumors (no statistical significance) and they should be designated separately (that is P2str). P3b bladder tumors with prostatic stromal invasion arising intraurethrally are indistinguishable from P4a tumors.

Adult↗
PubMed1996

Urethral recurrence in patients with orthotopic ileal neobladders.

PURPOSE: We identified the risk of urethral recurrence following cystectomy for transitions cell bladder carcinoma, stratified by pathological characteristics of the bladder tumor and type of urinary diversion. MATERIALS AND METHODS: The pathological characteristics and clinical courses of 174 men with a Kock ileal neobladder and 262 with a cutaneous urinary diversion were analyzed for time to urethral recurrence. RESULTS: Urethral recurrence was identified in 34 patients at a median of 1.6 years after cystectomy, for an overall 7.9% 5-year risk of recurrence. Carcinoma in situ (p = 0.71) and multifocality (p = 0.17) did not independently confer an increased risk of recurrence. Prostatic urethral involvement, particularly stromal invasion, significantly increased the probability of recurrence (p < 0.001). Patients with a Kock ileal neobladder had a significantly lower probability of recurrence compared to those with cutaneous diversion (p = 0.015), even when associated with prostatic urethral involvement. CONCLUSIONS: Patients with a Kock ileal neobladder have a lower risk of urethral recurrence than those with cutaneous urinary diversion, even when associated with a high risk pathological condition predicting increased risk of urethral recurrence.

Aged↗
PubMed1996

Phase I and pharmacokinetic study of oral UFT, a combination of the 5-fluorouracil prodrug tegafur and uracil.

UFT is an oral preparation combining the 5-fluorouracil (FU) prodrug tegafur (FT) and uracil (U) in a 1:4 ratio, which is commercially available in Japan for the treatment of breast and gastrointestinal cancers. We sought to determine the tolerance of daily oral UFT and to relate this tolerance to the pharmacokinetics of FT and/or the derived FU, while exploring the possibility of circadian FU kinetics contributing to the results. A 28-day schedule followed by 2 weeks rest was began at the initial level of 300 mg/m2/day administered either at 8 a.m. or at 6 p.m. At the following level, 400 mg/m2/day patients were randomly assigned to a split-dose administration or to the above single, timed dose administration. Intolerance to single dosing was clearly demonstrated, and only the split dosing was advanced to 500 mg/m2/day. When this level proved too toxic, 400 mg/m2 was studied further on a 7 a.m., 3 p.m., and 11 p.m. (every 8 h) schedule. Pharmacology was determined on selected patients. In the single dose administration, areas under the curves of FU were higher following p.m. dosing, although substantial interpatient variation was present. Toxicities (diarrhea and neutropenia) were more severe in patients receiving the drug in single daily doses. We conclude that the kinetics of FT are saturable, with disproportionate increases in area under the curve (and toxicities) as dose levels are increased. With divided dosing, tolerance improves. UFT at a dose of 400 mg/m2/day administered as three divided doses (every 8 h) is suitable for Phase II studies, although toxicity requiring cessation of drug administration prior to completion of 28-day cycles will occur in some patients.

Administration, Oral↗