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The physical properties of 59 anticancer agents have been examined with respect to solubility in tissue culture media, binding to ultrafiltration materials, and molecular absorbance and fluorescence behavior. Methods for dissolving these agents, which are compatible with in vitro sensitivity testing of human tumor cells to anticancer agents, are reported in this paper. The potential for anticancer agent binding to cellulose nitrate/cellulose acetate and teflon membrane ultrafilters was documented, and quantitation of these anticancer agents based upon absorbance and fluorescence spectroscopy was performed. Post-filtration quantitation of anticancer agents was found to be a reliable method for determining the actual drug concentrations available in tumor cell sensitivity testing in vitro. The properties documented herein are pharmacologically relevant parameters related to in vitro determinations of human tumor cell sensitivity to anticancer agents. [ABSTRACT FROM AUTHOR]

Deals with a study which aimed to determine whether nephrectomy affects survival in metastatic renal cell cancer patients. Methodology used in the study; Results and conclusion.

Background: The value of nephrectomy in metastatic renal-cell cancer has long been debated. Several nonrandomized studies suggest a higher rate of response to systemic therapy and longer survival in patients who have undergone nephrectomy.Methods: We randomly assigned patients with metastatic renal-cell cancer who were acceptable candidates for nephrectomy to undergo radical nephrectomy followed by therapy with interferon alfa-2b or to receive interferon alfa-2b therapy alone. The primary end point was survival, and the secondary end point was a response of the tumor to treatment.Results: The median survival of 120 eligible patients assigned to surgery followed by interferon was 11.1 months, and among the 121 eligible patients assigned to interferon alone it was 8.1 months (P=0.05). The difference in median survival between the two groups was independent of performance status, metastatic site, and the presence or absence of a measurable metastatic lesion.Conclusions: Nephrectomy followed by interferon therapy results in longer survival among patients with metastatic renal-cell cancer than does interferon therapy alone. [ABSTRACT FROM AUTHOR]

Extramammary Paget's Disease (EMPD) is a rare cutaneous, slow growing, intraepithelial adenocarcinoma that can be either primary (intraepithelial arising within the epidermis) or secondary (intraepithelial spread of a visceral carcinoma). Here we present the case of a 63-year-old male with EMPD of the glans penis stemming from underlying urothelial carcinoma. Our treatment decision elected for management with chemotherapy and local treatment with radiation therapy. Subsequent, review of the literature demonstrated a rare disease with a variety of underlying malignancies causing this secondary pathology. Caregivers should be aware of the association of Paget's disease and urothelial cancer and should have a high index of suspicion that erythematous penile lesions may represent Paget's disease and that penile biopsies should be performed early in this setting.

Purpose: The clinical and pathological features of solid or complex cystic renal masses in young adults have not been defined. We present our experience with patients 17 to 45 years old with such renal masses to define the incidence of malignant vs benign lesions, familial tendencies and clinical outcomes., Materials and Methods: The medical records of all patients 17 to 45 years old who presented with a solid or suspicious complex cystic renal mass at 2 tertiary care hospitals between 1988 and 2002 were retrospectively reviewed. Pertinent clinical information was compiled, including age, gender, mode of presentation, renal function, year and type of surgery, pathological analysis and survival data., Results: There were 114 evaluable patients who underwent a total of 119 nephrectomies. Mean patient age was 37.1 years and males comprised 56.1% of the population. Twelve patients had familial renal cell carcinoma (RCC), the von Hippel-Lindau syndrome. Mode of presentation for patients with sporadic disease was symptomatic (55.9%), incidental (35.3%) or unknown (8.8%). Radical nephrectomy, partial nephrectomy and nephroureterectomy were performed in 80 kidneys (67.2%), 37 (31.1%) and 2 (1.7%), respectively. Malignant lesions comprised 79.8% of all masses and 95.8% of these were renal cell carcinoma. Of the RCCs 75.8% were grade 1 or 2 and 89% were organ confined. Young women were much more likely than men to have a benign lesion (36.0% vs 9.5%, p <0.01) and the diversity of histologies was impressive (of the 24 total benign masses 9 were different tumor types). With an average followup of 38.3 months overall survival is 90.2%. Among patients with RCC 84.9% are alive and cancer-free, 11.6% are dead from disease and 3.5% are alive with recurrent disease., Conclusions: We report the largest known series of solid or suspicious complex renal masses in young adults. As expected, familial tumors are more common in this population. While RCC is the most common tumor, a wide variety of potential pathological outcomes are possible, particularly in women, who were much more likely to have a benign lesion. RCC in this patient population appears to have a favorable prognosis, despite symptomatic presentation in the majority of cases.

Manipulations capable of breaking host tolerance to induce tissue-specific T cell-mediated inflammation are of central importance to tumor immunotherapy and our understanding of autoimmunity. We demonstrate that androgen ablative therapy induces profuse T cell infiltration of benign glands and tumors in human prostates. T cell infiltration is readily apparent after 7-28 days of therapy and is comprised predominantly of a response by CD4+ T cells and comparatively fewer CD8+ T cells. Also, T cells within the treated prostate exhibit restricted TCR Vbeta gene usage, consistent with a local oligoclonal response. Recruitment/activation of antigen-presenting cells in treated prostate tissues may contribute to local T cell activation. The induction of T cell infiltration in prostate tissues treated with androgen ablation may have implications for the immunotherapeutic treatment of prostate cancer as well as other hormone-sensitive malignancies, including breast carcinoma.

Metastatic renal cancer is responsive in some cases to immunotherapeutic agents. Indications for nephrectomy in the face of metastatic disease have traditionally included palliation of symptoms caused by the primary tumor, and nephrectomy combined with metastatectomy in patients with resectable metastases. Recent findings from a Southwest Oncology Group trial strongly suggest that cytoreductive nephrectomy, combined with immunotherapy, may also result in improved survival in patients with unresectable metastases.

The role of cytoreductive surgery in patients with metastatic renal cancer remains controversial. Recent data from our Southwest Oncology Group trial suggest that cytoreduction confers an approximately 50% increase in median survival for such patients when they are treated with interferon-alfa-2b immunotherapy. The timing of cytoreduction, and in which patients it may be most applicable, are discussed herein.

Background: Dietary fatty acids may influence prostate carcinogenesis. Although the standard for assessing dietary effects in humans is the semiquantitative food-frequency questionnaire, the extent to which self-reported intake correctly ranks prostatic exposure is unknown., Objective: The objective was to examine the correlation between reported intakes of different fatty acids and their concentrations in prostate tissue., Design: This was a cross-sectional study of 52 men undergoing surgical resection of the prostate gland. Usual dietary intake of saturated, total unsaturated, oleic, and linoleic fatty acids over the previous year was estimated with use of a 122-item version of the Health Habits and History Questionnaire. Concentrations in prostate tissue were measured directly by use of gas chromatography in healthy tissue collected at the time of surgery and were expressed as a percentage of total fatty acids. Correlations with 4 measures of dietary intake [g/d, g/d adjusted for total daily energy intake, % of total fat (as g/d), and % of total energy] were evaluated by Spearman's rank-order correlation coefficients., Results: Linoleic acid concentrations in prostate tissue were significantly correlated with dietary intake expressed as g/d adjusted for total energy [r = 0.29 (95% CI: 0.03, 0.49), P = 0.04], % of total fat [r = 0.36 (0.14, 0.550), P = 0.008], and % of total energy [r = 0.28 (0.04, 0.49), P = 0.042], but not as g/d. Although mean concentrations of saturated, total unsaturated, and oleic fatty acids in prostate tissue resembled mean intakes for the group, prostatic concentrations did not correlate with individual intakes., Conclusion: Self-reported intake of fatty acids is a satisfactory marker of prostatic exposure at the group level, but, with the exception of linoleic acid, does not correctly rank individuals with respect to intensity of exposure.

Purpose: The consumption of various fatty acids has been associated with advanced stage and fatal prostate cancer. While numerous mechanisms have been postulated, to our knowledge there physiological data linking exposure and prognosis in humans are lacking. We examined prostatic levels of individual fatty acids in relation to the prevalence of histopathological characteristics associated with invasiveness and the risk of progression in 49 men undergoing radical prostatectomy for localized prostate cancer., Materials and Methods: Fatty acids were measured using capillary gas chromatography in fresh nonmalignant prostate tissue collected at surgery. Markers of invasiveness and increased risk of progression (Gleason sum 7 or greater, perineural invasion, anatomical or surgical margin involvement, extracapsular extension, seminal vesical involvement and stage T3 tumor) were evaluated separately. Each marker was dichotomized into a yes (case) and no (control) level with patients grouped accordingly. Mean concentrations were compared using the Wilcoxon rank sum test., Results: The percent of total prostatic polyunsaturated fat and polyunsaturated-to-saturated fat ratios were significantly lower in the presence of perineural invasion, seminal vesical involvement and stage T3 tumor (p = 0.02 to 0.049). alpha-Linolenic acid was significantly lower when tumor extended to an anatomical or surgical margin (p = 0.008). The omega-3 and omega-3-to-omega-6 fatty acid ratios were 1.5 to 3.3-fold lower in cases than in controls, reaching borderline significance in nearly all comparisons (p = 0.052 to 0.097). Saturated and monounsaturated fatty acids were not associated with the traits examined., Conclusions: These data suggest that polyunsaturated fatty acids and perhaps essential fatty acids in particular help to regulate prostate carcinogenesis in humans.

Purpose: We identify predictors of extraprostatic extension and positive surgical margins in patients with low risk prostate cancer (prostate specific antigen [PSA] 10 ng./ml. or less, biopsy Gleason score 7 or less and clinical stage T1c-2b)., Materials and Methods: From August 1997 to January 1999, 143 previously untreated patients underwent radical retropubic prostatectomy for clinically localized prostate cancer. A total of 62 patients were low risk, with PSA 10 ng./ml. or less, biopsy Gleason score 7 or less and clinical stage T1c-2b, and had sextant biopsy with separate pathological evaluation of each sextant cores. PSA, clinical stage, biopsy Gleason score, average percentage of cancer in the entire biopsy specimen, maximum percentage of cancer on the most involved core, number of cores involved and bilaterality were evaluated for association with extraprostatic extension, seminal vesicle involvement and positive surgical margins., Results: Of the 62 patients 13 (21%) had extraprostatic extension, 6 (10%) seminal vesicle involvement and 20 (32%) positive surgical margins. Average percentage greater than 10% and maximum percentage greater than 25% were associated with extraprostatic extension (p = 0.01 and 0.004, respectively). Average percentage greater than 10%, maximum percentage greater than 25%, more than 2 cores involved and bilaterality were associated with positive surgical margins (p = 0.007, 0.01, 0.002 and 0.03, respectively). On multivariate analysis maximum percentage remained the only independent predictor of extraprostatic extension (p = 0.03), and the number of cores involved remained an independent predictor of positive surgical margins (p = 0.01). Biopsy Gleason score, PSA and clinical stage did not correlate with extraprostatic extension or positive surgical margins in this patient population., Conclusions: In low risk prostate cancer the extent of biopsy involvement significantly correlates with the risk of extraprostatic extension and positive surgical margins. Biopsy information should be considered when selecting and modifying treatment modalities.

The role of cytoreductive nephrectomy in the management of metastatic renal cancer remains controversial. Recent trials, like SWOG 8949 have suggested the usefulness of this approach at least in selected patients with good performance status and other favorable indicators. The timing of cytoreductive nephrectomy has also been controversial and remains so to this time.

Amyloidosis of the ureter is a rare condition. It is even rarer when it involves both the ureter and bladder. The case presented is the second known case of combined amyloidosis of the bladder and ureter and the first combined case to be treated successfully by ileal ureter replacement. Historically, amyloidosis of the ureter has been treated by nephroureterectomy. Based on the benign nature of the disease, amyloidosis of the ureter is optimally treated with a kidney-sparing procedure such as ileal ureter replacement.

DNA analysis is becoming an important diagnostic and prognostic adjunct test in urinary cytology. The aim of this study was to compare the results of DNA flow cytometry (FCM) with the cytologic diagnosis of bladder washings (BW). DNA ploidy was evaluated in 251 BW. In 65 cases, follow-up surgical biopsies were available. Cytology results were classified as positive and negative, and FCM results were categorized as diploid and aneuploid. Both tests were evaluated independently. Cases were defined as discordant if the cytology was negative and FCM was aneuploid, or if the cytology was positive and FCM was diploid. All discordant cases were reviewed, and positive predictive values (PPV) for FCM and cytology were calculated for cases with follow-up biopsy results. Cytologic evaluation classified 181 cases as negative, with 175 of them diploid and 6 aneuploid; and 70 as positive, with 53 of them diploid and 17 aneuploid. Overall, there were 59 discordant cases (23.5%, with a confidence limit of 18.2-28.8%). Of 6 aneuploid/cytology-negative cases, biopsies were available in 4 cases and showed one grade 1, two grade 2, and one grade 3 urothelial carcinoma (UC). Reanalysis of these 6 cytology specimens showed 1 case that should have been interpreted as positive (false negative), 4 true negatives, and 1 polyoma virus infection. Out of 53 diploid/cytology-positive cases, biopsies were available in 45 cases and showed nine grade 1, 14 grade 2, three grade 3 UCs, 11 UCs in situ, and eight negative biopsies. The PPV for cytology was 85%, and the PPV for FCM was 95%. We concluded that FCM, which requires a large number of cells, often cannot detect small aneuploid populations, which are present particularly in cases of UC in situ., (Copyright 2000 Wiley-Liss, Inc.)

Purpose: Prostate specific antigen (PSA) exists in bound (complexed) and unbound (free) forms in serum. The percentage of free PSA enhances the specificity of PSA testing for prostate cancer detection. We evaluated the use of percent free PSA preoperatively to predict pathological stage., Materials and Methods: A total of 379 men with prostate cancer and 394 with benign prostatic disease 50 to 75 years old were enrolled in this prospective study at 7 medical centers. All subjects had a palpably benign prostate gland, serum PSA 4.0 to 10.0 ng./ml. and a histologically confirmed diagnosis. The Hybritech Tandem PSA and free PSA assays were used. Of the 379 cancer patients 268 (71%) underwent radical prostatectomy., Results: Higher percent free PSA levels were associated with more favorable histopathological findings in prostatectomy specimens. A value of 15% free PSA provided the greatest discrimination in predicting favorable pathological outcome. Organ confined cancer, Gleason sum less than 7 and small tumors (10% or less involvement of the prostate) were noted in 75% of patients with greater than 15% and only 34% with 15% or less free PSA (p<0.001). Multivariate logistic regression analysis revealed percent free PSA to be the strongest predictor of postoperative pathological outcome (odds ratio 2.25), followed by biopsy Gleason sum (2.06) and patient age (1.35). Total PSA was not predictive in this cohort but has been shown in prior studies to be predictive of outcome when a broader range of PSA values is evaluated., Conclusions: Percent free PSA may be used for risk assessment of the presence (diagnosis) and stage of prostate cancer in men with PSA between 4 and 10 ng./ml. Percent free PSA may be combined with PSA, digital rectal examination and biopsy findings to help predict postoperative pathological stage and grade, and may assist the patient and physician in making more informed treatment decisions.

A limited institution Phase II pilot study was performed using a very low-dose combination of daily s.c. interleukin (IL)-2 with IFN-alpha-2b in patients with advanced renal cancer in an attempt to duplicate or increase the response documented with higher dose schedules without the attendant toxicity profile. We selected a dose of IL-2 with documented immunological activity and combined it with clinically active low-dose IFN. Between August 1994 and September 1996, 19 patients with metastatic renal cell carcinoma, who had been judged incapable of tolerating high-dose i.v. IL-2, were treated with IL-2 (1 million units/m2/day) and IFN (1 million units/day), administered s.c. daily. All treatments were administered on an outpatient basis. Virtually all patients had bulky tumor burden with multiple sites of involvement, including five patients with bone metastases. No major objective responses were observed; however, one patient experienced a minor response lasting 13 months, with an associated improvement in performance status. Median survival was 6 months, and 1-year survival was 16%. Toxicity was generally mild and consisted almost entirely of constitutional symptoms. No serious grade 3 or 4 toxicity was observed, although two patients withdrew from treatment due to treatment-related fatigue. On therapy, mild eosinophilia but no lymphocytosis was noted; in fact, peripheral lymphocyte counts decreased, only to rebound after treatment was discontinued. No toxic deaths occurred. Despite the reasonable tolerability of this daily low-dose s.c. regimen, we conclude that this regimen is an ineffective treatment in metastatic renal cell carcinoma patients who are incapable of tolerating high-dose i.v. IL-2.

Purpose: To investigate the relationship of telomerase activity, telomere length, and DNA ploidy in high grade prostatic intraepithelial neoplasia (PIN)., Materials and Methods: Tissue samples were carefully microdissected to obtain adenocarcinoma or PIN-containing tissue free of cancer. Telomerase activity was measured using the PCR-based telomeric repeat amplification protocol (TRAP). Telomere length was estimated from Southern blots of telomere restriction fragments (TRFs). DNA ploidy of PIN and carcinoma was determined by image analysis of adjacent Feulgen stained tissue sections., Results: Telomerase activity was found in 4 of 25 samples (16%) of high grade PIN. All telomerase positive PIN foci had a diploid DNA content. Although 5 of 25 samples (25%) of high grade PIN foci analyzed were DNA aneuploid, none of these demonstrated telomerase activity. Telomerase positive foci of prostate carcinoma (69% of all cancer foci analyzed) displayed heterogeneity in TRF length, with a mean TRF length two kilobase pairs shorter than that of telomerase negative specimens., Conclusions: Telomerase activity is present in a low percentage of high-grade PIN foci, which are diploid by DNA content measurements.