Progression to detrusor muscle invasion during urothelial carcinoma surveillance is associated with poor prognosis.

OBJECTIVE: To evaluate survival in patients after radical cystectomy (RC) who presented with non-muscle-invasive urothelial carcinoma and progressed to muscle invasion during surveillance. Our secondary objective was to evaluate the association between clinical factors before RC and survival. PATIENTS AND METHODS: In all, 981 consecutive Mayo Clinic RC patients without a history of radiation or systemic chemotherapy were reviewed. Of these, 190 had RC after they progressed from non-muscle invasive disease to muscle invasion (progressed to ≥pT2). These patients were compared to 310 patients who had RC before muscle invasion (≤pT1), and 481 patients who had muscle invasion at initial presentation (presented with ≥pT2). Survival estimates were generated using the Kaplan-Meier method and compared using the log-rank test, while adjusted analyses were performed using Cox proportional hazard regression models. RESULTS: Patients who progressed to muscle invasion on surveillance had a higher risk of death than patients who initially presented with muscle invasion (overall survival hazard ratio [HR] 1.3; 95% confidence interval [CI] 1.0, 1.5). The estimated 5-year cancer-specific survival was 85.4% for patients presenting with ≤pT1, 52.9% for patients who progressed to ≥pT2, and 62.4% for patients who presented with ≥pT2 (P < 0.001). The corresponding 5-year overall survival rates were 70.0%, 42.1%, and 49.5% (P < 0.001). Of the patients who initially presented with non-muscle-invasive disease, progression to muscle invasion was associated with increased risk of cancer-specific death (adjusted HR 2.38; 95% CI 1.6, 3.5). Lack of information about patients who presented without muscle invasion and never received RC is the major limitation of this study. CONCLUSIONS: Despite close surveillance, many patients who progress to muscle invasion will die from bladder cancer. Patients who progress to muscle invasion on surveillance seem to have particularly aggressive disease and may benefit from multimodal treatments.

Downstaging to non-invasive urothelial carcinoma is associated with improved outcome following radical cystectomy for patients with cT2 disease.

INTRODUCTION: Pathologic stage is a critically important prognostic factor after radical cystectomy (RC) that is used to guide the use of secondary therapies. However, the risk of disease recurrence, for patients clinically diagnosed with muscle-invasive tumors who are found not to have muscle-invasive disease at RC are poorly defined. Therefore, we reviewed the long-term outcomes in patients who were downstaged to non-invasive urothelial carcinoma at time of RC. METHODS: We identified 1,177 consecutive patients with muscle-invasive urothelial carcinoma of the bladder who underwent radical cystectomy at our institution between 1980 and 1999 without neoadjuvant therapy. Postoperative disease recurrence and survival were estimated using the Kaplan-Meier method and compared using the log rank test. Cox proportional hazard regression models were used to analyze the impact of pathologic stage on survival. RESULTS: Pathologic downstaging to non-muscle invasive disease was identified in 538 (45.7 %) patients. The 10-year cancer-specific survival was 84.1, 77.4, 71.1 and 58.5 % for those with pT0, pTis, pT1 and pT2 tumors, respectively. On multivariate analysis, the risk of cancer-specific mortality was significantly decreased for patients with non-muscle invasive disease than those with organ-confined muscle invasion (RR-0.39; p = 0.002). There was no difference in disease-specific mortality among patients who had non-invasive (pT0, pTa, or pTis) disease (p = 0.19). CONCLUSIONS: Downstaging from clinical muscle-invasive bladder cancer to non-muscle invasive disease at RC is associated with a significant reduction in cancer-specific mortality. However, even patients with residual non-muscle invasive disease may suffer disease recurrence and require continued surveillance after surgery.

Patch test results may vary depending on where testing is performed: a comparison of patch test results from three geographically distinct sites in the USA.

BACKGROUND: Do patch test results vary from one part of the USA to another? Few reports directly compare the results of patch testing across centers within the USA. OBJECTIVES: Our objective was to compare results of patch testing from three geographically disparate Mayo Clinic sites in the USA to ascertain whether there are any differences in allergic patch test rates. METHODS: We retrospectively reviewed patch test results for patients tested with a standard allergen series using our enterprise-wide protocol for patch testing. We compared data collected from January 1, 2001, through to December 31, 2007, from our practice sites in the Midwest, Southwest, and Southeast regions of the USA. RESULTS: In total, 5063 patients underwent patch testing. The mean (standard deviation) number of allergens tested per patient was 70.3 (3.8) (range: 10-87; interquartile range: 68-73). Analyses were conducted separately for 72 allergens with positive reactions from at least 20 patients. Risk-adjusted positive reaction rates (RAPRRs) for 44 allergens differed significantly (P<0.05) among the geographic sites; RAPRRs differed significantly across all three sites for 11 allergens and between two of the three sites for 33 allergens. CONCLUSIONS: Allergic patch test rates differed among our three practice sites for many allergens. It is likely that many factors contributed to these observed differences, including variations in the population undergoing patch testing, variations in allergen exposure, and variations in climate.

Patch-testing with hairdressing chemicals.

BACKGROUND: Hairdressing chemicals may be associated with allergic contact dermatitis. OBJECTIVE: To review our experience of patch-testing with hairdressing chemicals. METHODS: We reviewed results from patients who underwent patch testing with our standard allergen series (including 15 hairdressing chemicals) and a supplementary "hairdresser series" (18 additional hairdressing chemicals) at Mayo Clinic (Rochester, MN; Scottsdale, AZ; and Jacksonville, FL) from January 1, 2000, through December 31, 2008. RESULTS: Two hundred ten patients (mean age, 53.8 years [SD, 16.9 yr]; female, 94.8%) were patch-tested. The most common sites of dermatitis were the scalp, face, and hands. Patients had widely varying occupations. The most common occupations were cosmetologist (10.5%), housewife (9.5%), and beautician (5.2%); 14.3% were retired. The hairdresser series detected 13 additional patients with allergies (6.4%; 204 patients tested with both series) who would not have been detected with the standard allergen series alone. The highest allergic patch-test rates in the supplemental hairdresser series were with ammonium persulfate (14.4%), 4-aminoazobenzene (13.4%), and pyrogallol (9.1%). CONCLUSIONS: Patch-testing with hairdressing-specific chemicals (standard series plus supplemental hairdresser series) was appropriate for numerous clinical situations and was not limited to patients in hair care occupations. The supplemental hairdresser series helped identify more patients than would have been identified with the standard series alone.

Long-term complications of conduit urinary diversion.

PURPOSE: We evaluated long-term surgical complications and clinical outcomes in a large group of patients treated with conduit urinary diversion. MATERIALS AND METHODS: We identified 1,057 patients who underwent radical cystectomy with conduit urinary diversion using ileum or colon at our institution from 1980 to 1998 with complete followup information. Patients were followed for long-term clinical outcomes and analyzed for the incidence of diversion specific complications. RESULTS: A total of 844 patients died at a median of 4.1 years (range 0.1 to 28.1) following cystectomy. Median followup of the surviving 213 patients was 15.5 years (range 0.3 to 29.1). There were 643 (60.8%) patients with 1,453 complications directly attributable to the urinary diversion performed with a mean of 2.3 complications per patient. Bowel complications were the most common, occurring in 215 patients (20.3%), followed by renal complications in 213 (20.2%), infectious complications in 174 (16.5%), stomal complications in 163 (15.4%) and urolithiasis in 162 (15.3%). The least common were metabolic abnormalities, which occurred in 135 patients (12.8%), and structural complications, which occurred in 122 (11.5%). Increasing age at cystectomy (HR 1.21, p <0.001), increasing Eastern Cooperative Oncology Group performance status (HR 1.23, p = 0.02) and recent era of surgery (HR 1.68, p <0.001) were significantly associated with a higher incidence of complications. CONCLUSIONS: Conduit urinary diversion is associated with a high overall complication rate but a low reoperation rate. Long-term followup of these patients is necessary to closely monitor for potential complications from the urinary diversion that can occur decades later.

Patch testing with a large series of metal allergens: findings from more than 1,000 patients in one decade at Mayo Clinic.

BACKGROUND: The standard allergen series used in patch testing contains metals that most commonly cause allergic contact dermatitis, but testing with additional metal allergens is warranted for select patients. OBJECTIVE: To report our experience with patch testing of metals. METHODS: We retrospectively analyzed outcomes of 1,112 patients suspected of having metal allergies. Patients were seen from January 1, 2000, through December 31, 2009. Patch testing was performed with 42 metal preparations (6 in the standard series, 36 in the metal series). RESULTS: Patch testing most commonly was performed for patients with oral disease (almost half the patients), hand dermatitis, generalized dermatitis, and dermatitis affecting the lips, legs, arms, trunk, or face. At least one positive reaction was reported for 633 patients (57%). Metals with the highest allergic patch-test reaction rates were nickel, gold, manganese, palladium, cobalt, Ticonium, mercury, beryllium, chromium, and silver. Metals causing no allergic patch-test reactions were titanium, Vitallium, and aluminum powder. Metals with extremely low rates of allergic patch-test reactions included zinc, ferric chloride, and tin. Reaction rates varied depending on metal salt, concentration, and timing of readings. CONCLUSION: Many metals not in the standard series were associated with allergic patch-test reactions. The many questions raised by these findings, concerning patch testing with individual metals, will be the subject of future studies.

Patch testing with natural rubber latex: the Mayo Clinic experience.

BACKGROUND: delayed hypersensitivity reactions to natural rubber latex (NRL) have been recognized. These reactions may contribute to allergic contact dermatitis. We therefore have undertaken patch testing of patients with NRL if they are suspected to have allergic contact dermatitis to rubber. OBJECTIVE: to review results of patch testing with NRL (January 1, 2000, through December 31, 2007). METHODS: patients suspected of having allergic contact dermatitis from rubber who underwent patch testing with NRL were identified retrospectively. For safety reasons, patients with immediate hypersensitivity to NRL were excluded from patch testing. RESULTS: of 148 patients patch-tested with NRL, 3 (2.0%) had an allergic patch-test reaction. CONCLUSIONS: NRL is as common a cause of allergic contact dermatitis as many of the other allergens included in a specialized rubber allergen series. Patients suspected to be allergic to rubber should be patch-tested with NRL (provided they do not have type 1 hypersensitivity to NRL).

Results of Goeckerman treatment for psoriasis in children: a 21-year retrospective review.

Goeckerman treatment has been used for the management of widespread psoriasis in children for several decades at Mayo Clinic. We aimed to review our institutional experience with the effectiveness of Goeckerman treatment for psoriasis in children. We retrospectively reviewed the records of pediatric patients who underwent Goeckerman treatment over a 21-year period (1983-2003). The main outcome measure was improvement in psoriasis. During the study period, 65 children received Goeckerman treatment for predominantly widespread, recalcitrant psoriasis. The mean age was 11.6 years (range, 3 mos to 18 yrs), and the female-to-male ratio was 2:1. Psoriasis improved in all patients: 55 patients (85%) had >80% clearance of their psoriasis. The only adverse effect was folliculitis, occurring in 27 patients (42%). Mean duration of follow-up was 2.6 years (range, 17 days-18.2 yrs); average duration of remission was 2.6 years (range, 2 mos-12.79 yrs). Goeckerman treatment is an effective treatment for widespread psoriasis in children.

Patch-testing with plastics and glues series allergens.

BACKGROUND: Few US studies have reported results of patch testing with plastics and glues. OBJECTIVE: To report our institution's results of testing patients suspected of allergy to plastics and glues with a comprehensive plastics and glues series and to compare these results with previously published data. METHODS: Retrospective review of results of patch-testing with plastics and glues allergens at our institution between 2000 and 2007. In total, 444 patients were patch-tested with up to 56 plastics and glues allergens in the specialized series and up to five plastics and glues allergens in a baseline series. Positive-reaction rates were compared to other patch testing reports. RESULTS: Of patients, 97 (22%) had irritant reactions, and 201 (45%) had at least one allergic reaction. Bis(2-dimethylaminoethyl) ether 1%, benzoyl peroxide 1%, epoxy resin, bisphenol F 0.25%, 2-hydroxyethyl methacrylate 2%, and 2-hydroxyethyl acrylate 0.1% had the highest allergy reaction rates. Testing with specialized series identified 193 patients with plastics and glues allergy, of whom 162 were not identified by testing with baseline series alone. CONCLUSION: For patients suspected of allergy to plastics and glues, patch-testing with specialized series of plastics and glues allergens is an important adjunct to patch-testing with baseline series.

Results of patch testing to personal care product allergens in a standard series and a supplemental cosmetic series: an analysis of 945 patients from the Mayo Clinic Contact Dermatitis Group, 2000-2007.

BACKGROUND: Patch testing to a standard screening series of allergens in combination with supplemental cosmetic allergens is often used to diagnose allergic contact dermatitis due to personal care products. OBJECTIVE: To report results of patch testing to skin care product allergens contained in a standard series and a supplemental cosmetic series and to compare efficacy of this combined series in detecting positive reactions to personal care product allergens with the efficacy of various standard screening series. METHODS: Positive reaction rates to skin care product allergens were tabulated for patients who underwent patch testing to both standard and cosmetic series allergens at Mayo Clinic between 2000 and 2007. Data were compared with skin care allergens detected on standard screening series, including the thin-layer rapid use epicutaneous (TRUE) test. RESULTS: Of 945 patch-tested patients, 68.4% had at least one positive reaction and 47.3% had at least two positive reactions. Also, 49.4% of patients reacted to at least one preservative; 31.2% reacted to at least one fragrance/botanical additive. Compared with use of our standard series and cosmetic series, use of the TRUE test would have missed 22.5% of patients with preservative allergy, 11.3% with fragrance/botanical allergy, and 17.3% with vehicle allergy. LIMITATIONS: Various allergens tested over time, patch test reading by residents, and lack of confirmation of allergen in personal care products. CONCLUSION: Standard patch-test screening series miss a substantial number of patients with skin care product ingredient allergy.

Multifactorial, site-specific recurrence model after radical cystectomy for urothelial carcinoma.

BACKGROUND: A scoring algorithm of site-specific disease recurrence after cystectomy for urothelial carcinoma was designed. METHODS: Identified were 1388 patients who underwent radical cystectomy for nonmetastatic urothelial carcinoma between 1980 and 1998. Clinical, surgical, and pathologic features were evaluated for associations with 4 locations of site-specific disease recurrence: upper urinary tract, abdomen/pelvis, thoracic region, and bone. Recurrence-free survival rates were estimated using the Kaplan-Meier method. Cox proportional hazards models were fit to test associations with disease recurrence. RESULTS: A total of 493 (35.5%) patients experienced at least 1 recurrence. There were 67, 388, 143, and 145 patients with recurrences to the upper tract, abdomen/pelvis, thoracic region, and bone at a median of 3.1 years, 1.1 years, 1.3 years, and 1.0 years, respectively. Pathologic T4 stage (hazard ratio [HR], 2.84; P=.006), positive ureteral margins (HR, 5.71; P<.001), and multifocality (HR, 2.07; P=.009) were found to be independent predictors of upper tract recurrence. Pathologic T3 (HR, 2.30; P<.001) and T4 stage (HR, 3.55; P<.001), lymph node invasion (HR, 1.97; P<.001), extent of lymphadenectomy (pNx [HR, 1.66; P=.002] and <10 lymph nodes [HR, 1.52; P<.001]), multifocality (HR, 1.80; P<.001), and prostatic involvement (HR, 1.45; P=.019) were found to be independent predictors of abdominal/pelvic recurrence. Features independently associated with thoracic recurrence included pathologic T3 (HR, 2.61; P<.001) and T4 (HR, 3.39; P<.001), lymph node invasion (HR, 2.64; P<.001), extent of lymphadenectomy (pNx [HR, 1.89; P=.019] and <10 lymph nodes [HR, 1.58; P<.030]), and multifocality (HR, 1.79; P<.001). Pathologic T3 (HR, 3.45; P<.001) and T4 stage (HR, 3.87; P<.001), lymph node invasion (HR, 1.79; P=.006), occupational exposure to radiation (HR, 2.97; P=.003), and a positive urethral margin (HR, 2.28; P=.039) were found to be independent predictors of osseous recurrence. Macroscopic hematuria (HR, 0.52; P=.009) and obesity (HR, 0.59; P=.027) were found to be protective and negatively associated with upper tract and osseous recurrence, respectively. Scoring algorithms to predict the likelihood of disease recurrence to these sites were developed using regression coefficients from the multivariable models. CONCLUSIONS: Scoring algorithms based on independent predictors of site-specific recurrence were presented. These models may be used to tailor postoperative surveillance to the individual patient based upon clinicopathologic features at the time of cystectomy.

An 8-year retrospective review of patch testing with rubber allergens: the Mayo Clinic experience.

BACKGROUND: Allergic contact dermatitis from rubber chemicals is increasingly recognized. OBJECTIVE: To review the results of patch testing with rubber allergens from January 1, 2000, through December 31, 2007. METHODS: Patients who underwent patch testing with a specialized series of rubber allergens were identified. RESULTS: In total, 773 patients (64.2% female; mean age, 48.6 years) were patch-tested with a rubber series (27 allergens), and 739 (95.6%) were concomitantly patch-tested with a standard allergen series. Commonly affected sites of dermatitis were the hand (49.7%), foot (15.9%), leg (12.0%), and arm (10.9%). The most common occupations were health care worker (16.3%) and homemaker (6.5%); 11.3% were retired. The rate of allergic reaction to at least one rubber allergen was 245 of 773 (31.7%). The allergens that most commonly yielded positive reactions were 4,4-dithiodimorpholine 1% (28/286 [9.8%]), thiuram mix (56/739 [7.6%]), and diphenylguanidine 1% (57/759 [7.5%]). CONCLUSION: Rubber is a frequent cause of allergic contact dermatitis. Patch testing with a rubber series improved the ability to diagnose allergic contact dermatitis caused by rubber.

Significance of distal ureteral margin at radical cystectomy for urothelial carcinoma.

PURPOSE: Urothelial carcinoma develops from a diffusely susceptible mucosa and, thus, patients who undergo cystectomy are at risk for upper tract recurrence. Management of the distal ureter at cystectomy remains controversial and the impact of a sequential sectioning strategy remains unclear. MATERIALS AND METHODS: We identified 1,397 patients who underwent radical cystectomy for nonmetastatic urothelial carcinoma from 1980 to 1998. All patients underwent frozen section analysis of the distal ureteral specimen. When positive, additional specimens were obtained. We evaluated the impact of a positive ureteral margin and the effect of ultimately obtaining a negative margin after sequential resection. RESULTS: At last followup 432 patients (31%) had died of urothelial carcinoma a median of 1.8 years after cystectomy. Median followup in the 315 patients alive at last evaluation was 14.0 years. A total of 178 patients (12.7%) had a positive initial ureteral margin and only 31 (2.2%) had a positive final resection margin. Associations of margin status with overall and cancer specific survival were not statistically significant. Of 1,397 patients 69 (4.9%) experienced upper tract recurrence at a median of 3.1 years. Positive initial margin status and final margin status were associated with upper tract recurrence (p <0.001). CONCLUSIONS: Patients with positive ureteral margins at cystectomy are at increased risk for upper tract recurrence. With a serial sectioning strategy most positive initial margins can be converted to negative final margins. Patients who undergo conversion to a negative final margin with serial sectioning are at decreased risk for upper tract disease.

Thioguanine nucleotides and thiopurine methyltransferase in immunobullous diseases: optimal levels as adjunctive tools for azathioprine monitoring.

OBJECTIVE: To prospectively determine optimal levels of 6-thioguanine nucleotide for disease remission in patients with immunobullous disease treated with azathioprine. DESIGN: Prospective, longitudinal study. Laboratory tests and clinical evaluations were performed monthly for 6 months and then every 2 to 3 months (median follow-up, 13.4 months). SETTING: Tertiary care medical center. PATIENTS: Twenty-seven patients with immunobullous disease treated with azathioprine were enrolled during a 2-year period. Twelve met the criteria for evaluation of optimal levels of 6-thioguanine nucleotide. MAIN OUTCOME MEASURES: Blood levels of 6-thioguanine nucleotide, 6-methylmercaptopurine, and thiopurine methyltransferase by polymerase chain reaction and enzyme activity were measured longitudinally during treatment. RESULTS: The range of 6-thioguanine nucleotide was 48 to 457 pmol/8 x 10(8) red blood cells (RBCs), with an average optimal level of 190.7 pmol/8 x 10(8) RBCs for all patients. The mean optimal levels were 179.4 and 205.6 pmol/8 x 10(8) RBCs for pemphigus and pemphigoid, respectively. Limited disease required less 6-thioguanine, with a mean of 145.3 pmol/8 x 10(8) RBCs. Longitudinal induction of thiopurine methyltransferase activity was observed during treatment. Patients with recalcitrant disease showed higher induction of enzyme activity (with an increase of 9.1 to 23.6 U/mL of RBCs above baseline) than did those with responsive disease. CONCLUSIONS: Optimal levels of 6-thioguanine nucleotide metabolites for disease remission in dermatology patients are 150 to 300 pmol/8 x 10(8) RBCs. High levels of the inactive metabolite 6-methylmercaptopurine and induction of thiopurine methyltransferase are associated with recalcitrant disease.

Expression and significance of androgen receptor coactivators in urothelial carcinoma of the bladder.

Urothelial carcinoma (UC) of the bladder is approximately three times more common in men than women. While the etiology for this gender difference in incidence remains unknown, a role for androgen receptor (AR) signaling has been suggested. The mechanisms by which AR activity is regulated in UC cells, however, are largely elusive. Here, we explore the significance of coregulators that are critical for the formation of a functional AR transcriptional complex, in UC cells. Using two AR-positive UC cell lines, TCC-SUP and UMUC3, we demonstrate the expression of the coactivators NCOA1, NCOA2, NCOA3, CREBBP, and EP300 in UC cells. small interfering RNA-mediated knockdown of the AR or any of these coactivators markedly impacted cell viability and abrogated androgen-dependent cell proliferation. Noteworthy, contrary to AR-positive prostate cancer cells, expression of these AR-associated coactivators was not androgen regulated in UC cells. To assess the clinical relevance of coactivator expression, we performed immunohistochemistry on paraffin-embedded sections from 55 patients with UC of the bladder. We found that while 24 out of 55 (44%) of tumors expressed the AR, each of the coactivators was expressed by 85-100% of the bladder cancers. Moreover, we noted a significant downregulation of NCOA1 expression in tumors versus adjacent, non-tumor bladder urothelium, with a mean of 68% (range 0-100) of tumor cells demonstrating NCOA1 staining versus a mean of 81% (range 0-90) of non-tumor cells (P=0.03). Taken together, our data suggest an important role for AR-associated coactivators in UC and point toward differences in the regulation of AR activity between bladder and prostate cancer cells.

Functional and oncological outcomes after orthotopic neobladder reconstruction in women.

OBJECTIVE: To review our experience with orthotopic neobladder reconstruction (ONR) in women, highlighting functional and oncological outcomes, as ONR has been used increasingly for urinary diversion in women after radical cystectomy (RC), largely due to a better understanding of the natural history of urothelial cell carcinoma (UCC) and of the anatomy underlying the female continence mechanism, but defining the safety and long-term efficacy of ONR remain important to expanding its use. PATIENTS AND METHODS: We identified 59 women who had RC with ONR between 1995 and 2006 at the Mayo Clinic. Their records were reviewed for clinicopathological demographics, and functional and oncological outcomes. RESULTS: The median (range) age at surgery of the women was 62 (20-82) years, and the median follow-up was 29.2 (1-141) months. Fifty-three women had RC for malignant disease, including UCC in 47. Five women (8.5%) required resection of the anterior vaginal wall during surgery, while 39 (66%) had concurrent hysterectomy. One patient had a positive surgical margin, at the left distal ureter, on final pathology. Thirteen (22%) patients had perioperative complications, including two (3%) who required reoperation. In addition, three patients (5%) developed a neobladder-vaginal fistula after RC with ONR, requiring surgical repair. At the last follow-up, daytime urinary continence (defined as needing no pads) was reported by 44/49 (90%) patients, while 28/49 (57%) had achieved continence at night. Seventeen (31%) patients required intermittent self-catheterization to facilitate emptying of the neobladder. Fifteen (28%) women had recurrence of disease, at a median of 8 (2-36) months after ONR, including seven (13%) who developed a pelvic recurrence. Twelve (20%) patients died during the follow-up, with four (8%) dying from UCC at a median of 14 (11-65) months after surgery. CONCLUSION: ONR provides a safe and effective option for urinary diversion in women, with oncological and functional outcomes similar to those for men. Thus, the technique remains a preferred option for urinary diversion in appropriately selected women treated with RC.

T-cell coregulatory molecule expression in urothelial cell carcinoma: clinicopathologic correlations and association with survival.

PURPOSE: Aberrant expression of T-cell coregulatory molecules has been investigated as a mechanism by which certain cancers may evade host immune surveillance. We evaluated expression of the T-cell coregulators B7-H1, B7-H3, and PD-1 in urothelial cell carcinoma (UCC) of the bladder. EXPERIMENTAL DESIGN: Immunohistochemistry for B7-H1, B7-H3, and PD-1 was done on paraffin-embedded sections from 318 consecutive patients with UCC who underwent radical cystectomy. Expression was correlated with clinicopathologic outcomes and postoperative survival. RESULTS: B7-H3 was widely expressed in UCC, as 222 of 314 (70.7%) tumors showed positive staining. Expression of B7-H3 in UCC was significantly increased compared with adjacent, nontumor urothelium, as a median of 70% of tumor cells expressed B7-H3, compared with 20% of cells in nontumor specimens (P < 0.001). The increase in B7-H3 expression was independent of tumor stage (P = 0.13). Expression of B7-H1 by UCC tumors (P < 0.001) and PD-1 by tumor-infiltrating lymphocytes (P = 0.012) were significantly associated with increased pathologic stage. Patients who had received intravesical bacillus Calmette-Guerin before cystectomy tended to show increased expression of B7-H3 (P = 0.023) and PD-1 (P = 0.071) but were less likely to express B7-H1 (P = 0.027). Moreover, for the subset of patients with organ-confined disease (n = 167), B7-H1 expression independently predicted all-cause mortality after cystectomy (hazard ratio, 3.18; 95% confidence interval, 1.74-5.79; P < 0.001). CONCLUSIONS: B7-H3 is highly expressed in UCC across tumor stages, whereas B7-H1 and PD-1 expression are associated with advanced disease. B7-H1 expression predicts mortality after cystectomy for patients with organ-confined tumors. These molecules may represent novel diagnostic or prognostic markers, as well as therapeutic targets, for patients with UCC.

Delayed patch test reading after 5 days: the Mayo Clinic experience.

BACKGROUND: Some patients may have delayed allergic patch test reactions that are not identified with a typical 5-day reading protocol. OBJECTIVE: To identify allergens with delayed-positive reactions and to determine whether a late reading (day 7-9) can be substituted for the day-5 reading. METHODS: We retrospectively reviewed medical records of patients who underwent patch testing for suspected allergic contact dermatitis from October 1997 through December 2006 and returned for delayed readings between days 7 and 10 or beyond. (This cohort was predominantly patients with suspected allergies to metals and corticosteroids). RESULTS: A total of 36,064 individual reactions (471 allergens, 372 patients) were interpreted on day 5 and at least once during days 7 through 21. We analyzed the 170 allergens that were each tested in at least 50 patients. The 4 allergens with the highest percentage of delayed-positive reactions were gold sodium thiosulfate 0.5% (delayed-positive reactions in 22/353 patients), dodecyl gallate 0.25% (6/105), palladium chloride 2% (8/194), and neomycin sulfate 20% (10/253). We observed a low number of delayed-positive readings for p-phenylenediamine 1% (1/251) and for corticosteroids. Reactions to certain preservative and fragrance allergens dissipated after the day-5 reading. Most reactions that dissipated after day 5 were mild, whereas the reactions that became apparent after day 5 were strong. LIMITATIONS: This was a retrospective study. Most patients had suspected allergies to metals and corticosteroids. CONCLUSION: Late patch test readings (day 7 or beyond) were useful when interpreting reactions to metals and topical antibiotics, but it was not useful in the diagnosis of reactions to other allergens, including topical corticosteroids. Because reactions to certain fragrance and preservative allergens may dissipate after 5 days, patch test reactions therefore are optimally read at days 3 and 5, but an additional reading on day 7 or beyond is useful if patch tests to metals and topical antibiotics are performed.

Changing trends and allergens in the patch test standard series: a mayo clinic 5-year retrospective review, january 1, 2001, through december 31, 2005.

OBJECTIVE: To present and interpret results of patch testing with the Mayo Clinic standard series over 5 years. DESIGN: Retrospective study. A standardized patch testing technique was used. Data were recorded on a standardized computer program from January 1, 2001, to December 31, 2005, and analyzed. SETTING: Tertiary referral center. PATIENTS: Patients who were referred for patch testing. INTERVENTION: Patch testing with the "standard series," ie, a standard series of allergens used by most clinicians to identify the most common offending allergens in patients with allergic contact dermatitis. MAIN OUTCOME MEASURES: Number of patients patch tested, allergens used over this period, and rates of allergic patch test reactions to allergens. RESULTS: A total of 3854 patients (mean age, 55.1 years; age range, 6.2-99.4 years; 2576 female [66.8%]) were tested. All dermatologists in the department performed patch testing. The mean number of allergens included was 69.3 (range, 6-87). There were 2664 patients with at least 1 positive reaction (69.1%) and 1933 with 2 or more positive reactions (50.2%). Metals, fragrances, topical antibiotics, preservatives, and individual allergens used in hair-care products, topical corticosteroids, glues, plastics, and rubber were still the most common allergen groups associated with allergic patch test reactions. CONCLUSIONS: We describe the structure of the patch testing service at our referral center. Ongoing analysis of our patch test reaction rates allows us to recommend broad, clinically relevant, and up-to-date allergens for testing.

Population-based case-control study of PSA and DRE screening on prostate cancer mortality.

OBJECTIVES: The efficacy of screening for prostate cancer (PCa) with digital rectal examination (DRE) and prostate-specific antigen (PSA) measurement has not been proved in randomized clinical trials. In an earlier case-control study, we found that DRE might reduce PCa mortality. The present case-control study assessed the association between PSA and DRE testing and PCa mortality. METHODS: The case subjects included 74 Olmsted County residents who had died from 1992 to 2005 with PCa as the underlying cause of death. From 1 to 3 community control subjects (alive at time of case subject's death) were matched to each case subject. The medical records were reviewed to identify DREs and PSA determinations performed 0 to 5 years before the date the case was diagnosed (index date). Tests performed in the absence of symptoms were considered to be "screening tests." Conditional logistic regression analysis was used to estimate the odds ratios and 95% confidence intervals for the association of screening (defined in multiple ways) and PCa mortality. RESULTS: From 1 to 5 years before the index date, control subjects were more likely than case subjects to have undergone a previous screening PSA test or DRE (81.3% versus 60.8%, P = 0.0005). The unadjusted odds ratio associated with a previous screening PSA test or DRE was 0.34 (95% confidence interval 0.18 to 0.63), and the odds ratio adjusted for potential confounders was 0.35 (95% confidence interval 0.17 to 0.71). PSA testing was frequently done in conjunction with DRE, making evaluation of the individual effects difficult. CONCLUSIONS: The results of this case-control study suggest a potential benefit of screening by PSA testing and/or DRE on PCa mortality.