Purpose: Interindividual differences in DNA repair capacity not only modify individual susceptibility to carcinogenesis, but also affect individual response to cancer treatment. Nucleotide excision repair (NER) is one of the major DNA repair pathways in mammalian cells involved in the removal of a wide variety of DNA lesions. Polymorphisms in NER genes may influence DNA repair capacity and affect clinical outcome of bladder cancer treatment.Experimental Design: To test the influence of NER gene polymorphisms on superficial bladder cancer outcome (recurrence and progression), we conducted a follow-up study of 288 patients with superficial bladder cancer. Median follow-up among patients who were recurrence-free at the end of observation was 21.7 months from diagnosis. The specific polymorphic loci examined include XPA [A/G at 5' untranslated region (UTR)], XPC (poly AT, Ala(499)Val, Lys(939)Gln, XPD (Asp(312) Asn, Lys(751)Gln), XPG (His(1104)Asp), ERCC 1 (G/T at 3' UTR), and ERCC6 (Met(1097)Val, Arg(1230)Pro).Results: The ERCC6 (Met(1097)Val) polymorphism had a significant impact on recurrence: carriers of at least one variant allele (Val) had a significantly higher recurrence risk than carriers of the wild-type allele (Met/Met; hazard ratio, 1.54; 95% confidence interval, 1.02-2.33). There were no overall statistically significant differences in the distributions of the other polymorphisms between patients with and without recurrence. However, when we combined these variant genotypes, there was a significant trend for an increased recurrence risk with an increasing number of putative high-risk alleles. Using individuals with five or fewer putative high-risk alleles as the reference group, individuals with six to seven risk alleles and individuals with eight or more risk alleles had higher recurrence risks, with hazard ratios of 0.92 (0.54-1.57) and 2.53 (1.48-4.30), respectively (P for trend < 0.001). There was also a significant trend for shorter recurrence-free survival time with increasing number of variant alleles (log rank test, P = 0.0007). When we stratified the patients according to intravesical Bacillus Calmette-Guerin treatment, we found a significant trend for shorter recurrence-free survival time in patients with variant alleles of XPA or ERCC6 polymorphisms who received Bacillus Calmette-Guerin treatment (log rank test, P = 0.078 and 0.022, respectively). There were no significant individual or joint associations between these polymorphisms and progression.Conclusions: These data suggest that interindividual differences in DNA repair capacity may have an important impact on superficial bladder cancer recurrence. A pathway-based approach is preferred to study the effects of individual polymorphism on clinical outcomes.

BACKGROUND. Frequently, a renal mass is identified when patients with cancer undergo studies for staging or surveillance. In determining whether it represents a metastasis, patients are frequently subjected to percutaneous renal biopsies. The authors evaluated their experience with this dilemma to formulate management guidelines.METHODS. The authors reviewed the medical records of 100 consecutive patients with nonrenal malignancies diagnosed with renal masses at presentation or follow-up. Renal mass histology was available for all patients after nephrectomy or biopsy. Clinical characteristics were assessed to identify factors predictive for a renal metastasis versus a primary renal neoplasm.RESULTS. The only factors predictive of a metastasis to the kidney were progression of the nonrenal malignancy and lack of enhancement of the renal mass (P < 0.0001). Forty-six patients (46%) had evidence of progression of their nonrenal malignancy in addition to the renal mass. In these patients, the probability of a metastasis to the kidney was 86% (95% confidence interval [CI], 57.2-98.2%) without renal mass enhancement and 32% (95% CI, 14-55%) with enhancing renal masses. None of the 54 patients without signs of progression of their nonrenal malignancy proved to have metastases to the kidney, regardless of the imaging characteristics of the mass (zero probability; 95% CI, 0-7%; P < 0.001).CONCLUSIONS. in patients presenting with renal masses and another clinically localized malignancy, renal mass biopsies were not indicated, as the mass rarely represented a metastasis. These patients may opt for close surveillance or extirpation based on the prognosis of their nonrenal malignancy. Cancer 2004;101:2195-201. (C) 2004 American Cancer Society.

PURPOSE:We previously demonstrated that overexpression of interleukin 8 (IL-8) in human transitional cell carcinoma (TCC) resulted in increased tumorigenicity and metastasis. This increase in tumor growth and metastasis can be attributed to the up-regulation in the expression and activity of the metalloproteinases MMP-2 and MMP-9.EXPERIMENTAL DESIGN:To investigate whether targeting IL-8 with a fully human anti-IL-8 antibody (ABX-IL8) could be a potential therapeutic strategy for controlling TCC growth, we studied its effects on TCC growth in vitro and in an in vivo mouse model. Human TCC cell lines 253J B-V and UM UC3 (high IL-8 producers), 253J (low IL-8), and 253J transfected with the IL-8 gene (high producer) were used.RESULTS:ABX-IL8 had no effect on TCC cell proliferation in vitro. However, in the orthotopic nude mouse model, after 4 weeks of treatment (100 micro g/week, i.p.), a significant decrease in tumor growth of both cell lines was observed. IL-8 blockade by ABX-IL8 significantly inhibited the expression, activity, and transcription of MMP-2 and MMP-9, resulting in decreased invasion through reconstituted basement membrane in vitro. The down-regulation of MMP-2 and MMP-9 in these cells could be explained by the modulation of nuclear factor-kappaB expression and transcriptional activity by ABX-IL8.CONCLUSIONS:Our data point to the potential use of ABX-IL8 as a modality to treat bladder cancer and other solid tumors, either alone or in combination with conventional chemotherapy or other antitumor agents.

Purpose: Locally recurrent prostate cancer can be a debilitating disease. Perineal pain associated with rectal involvement by prostate cancer is difficult to palliate by conventional methods. We describe a group of patients who had intractable perineal pain due to locally recurrent prostate cancer and underwent total pelvic exenteration for palliation.Materials and Methods: We retrospectively reviewed the data for men who underwent total pelvic exenteration with urinary and colonic diversion at our institution between October 1995 and October 2002 for the relief of perineal pain from prostate cancer. Patients were selected for consideration for surgical extirpation on the basis of the presence of biopsy proven recurrent prostate cancer and evidence of rectal invasion on sonography. All patients received radiation therapy and hormonal therapy and had intractable perineal or pelvic pain resistant to narcotics.Results: A total of 14 men underwent total pelvic exenteration for palliation during the 7-year period evaluated. There were no perioperative deaths. There were 7 postoperative events, including pulmonary embolus in 2 patients, and ileus, wound infection, cholecystitis, stomal stenosis and pelvic abscess in 1 patient each. After exenteration all patients had significant relief of pain and 11 (79%) had complete relief of pain symptoms. For these 11 patients the average symptom-free period was 14.1 months (range 3 to 36). Seven patients eventually died of disease, with the median period from exenteration to death being 24 months.Conclusions: Total pelvic exenteration is effective therapy for palliation of perineal pain associated with locally recurrent prostate cancer and can also effectively palliate other local symptoms such as hematuria, ureteral obstruction, voiding dysfunction and rectal incontinence. This procedure can be performed with acceptable morbidity in a highly select group of patients.

The purpose of the study was to determine the accuracy of the monoclonal antibody (Mab) [Prostascint, Cytogen, Inc.] scan for the detection of nodal metastases using histologic examination of surgical lymphadenectomy specimens as the standard of reference. We reviewed the records of 31 patients who had undergone biopsy after monoclonal antibody scan. Histologic evaluation was obtained for a total of 31 patients and 43 pathology samples. When analyzed by surgical site, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the Mab scan were 94%, 42%, 53%, 92% and 65%, respectively. When analyzed by individual patient, the same data for the Mab scan were 100%, 33%, 62%, 100% and 68%, respectively. Current noninvasive studies are not sufficiently accurate to reliably determine the presence of metastatic nodal disease from prostate cancer. This series illustrates the importance of rigorous clinical evaluation of future methods that are designed to detect microscopic metastatic disease of any neoplasm.

No AccessJournal of UrologyCLINICAL UROLOGY: Case Reports1 Oct 2002Ventral Bladder Hernia Following Tubal Ligation Alberto A. Peña, Carlos E. Bermejo, and Ian M. Thompson Alberto A. PeñaAlberto A. Peña More articles by this author , Carlos E. BermejoCarlos E. Bermejo More articles by this author , and Ian M. ThompsonIan M. Thompson More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)64491-6AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Ventral Bladder Hernia Following Tubal Ligation." The Journal of Urology, 168(4 Part 1), p. 1502 References 1 : Repair of urinary bladder herniation. Am J Surg1944; 63: 69. Crossref, Google Scholar 2 : Ventral bladder hernia following Marshall-Marchetti-Krantz procedure for stress urinary incontinence. Urology1986; 28: 114. Crossref, Medline, Google Scholar 3 : Bladder hernias. Urology1980; 15: 127. Crossref, Medline, Google Scholar From the Division of Urology, University of Texas Health Science Center, San Antonio, Texas© 2002 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited by Varnell B, Bachman S, Quick J, Vitamvas M, Ramshaw B and Oleynikov D (2008) Morbidity associated with laparoscopic repair of suprapubic herniasThe American Journal of Surgery, 10.1016/j.amjsurg.2008.08.006, VOL. 196, NO. 6, (983-988), Online publication date: 1-Dec-2008. Volume 168Issue 4 Part 1October 2002Page: 1502 Advertisement Copyright & Permissions© 2002 by American Urological Association, Inc.Keywordshernia, ventralpostoperative complicationsbladderMetrics Author Information Alberto A. Peña More articles by this author Carlos E. Bermejo More articles by this author Ian M. Thompson More articles by this author Expand All Advertisement PDF downloadLoading ...