Impact of clinical and histopathological parameters on disease specific survival in patients with collecting duct renal cell carcinoma: development of a disease specific risk model.

PURPOSE: Collecting duct renal cell carcinoma is a rare, aggressive histological subtype of renal cell carcinoma. Since few groups have evaluated the oncological prognosis in these patients based on clinical and pathological parameters, we assessed parameters prognostic for disease specific mortality. MATERIALS AND METHODS: From a cohort of 14,047 patients with renal cell carcinoma we retrieved the records of 95 with collecting duct renal cell carcinoma at a total of 16 European and American centers of the CORONA (Collaborative Research on Renal Neoplasms Association) and SATURN (Surveillance and Treatment Update Renal Neoplasms) projects, and another 2 centers. Multivariable Cox regression analysis was applied to determine the influence of parameters on disease specific mortality. Median followup was 48.1 months (IQR 24-103). RESULTS: The disease specific survival rate at 1, 2, 5 and 10 years was 60.4%, 47.3%, 40.3% and 32.8%, respectively. American Society of Anesthesiologists (ASA) score 3-4, tumor size greater than 7 cm, stage M1, Fuhrman grade 3-4 and lymphovascular invasion independently predicted disease specific mortality. Based on these parameters, patients were divided into 26 (27%) at low, 13 (14%) at intermediate and 56 (59%) at high risk with a 5-year disease specific survival rate of 96%, 62% and 8%, respectively (bootstrap corrected c-index 0.894, 95% CI 0.820-0.967, p <0.001). CONCLUSIONS: While patients with collecting duct renal cell carcinoma are commonly diagnosed at advanced stage and have poor prognosis after surgery, a subset has excellent survival. Histopathological features can help risk stratify patients based on the described, highly accurate risk model to predict disease specific mortality, facilitating patient counseling and risk based clinical decision making for adjuvant therapy and clinical trial inclusion.

Ki-67, mini-chromosome maintenance 2 protein (MCM2) and geminin have no independent prognostic relevance for cancer-specific survival in surgically treated squamous cell carcinoma of the penis.

UNLABELLED: What's known on the subject? and what does the study add?: Only little and partly contradictory data are currently published about the prognostic role of immunohistochemically detectable proliferation-associated biomarkers in surgically treated squamous cell carcinoma of the penis (SCCP), and no data are available at present about their usefulness for refining the delineation between different Broders' grading categories (e.g. still G2 or just G3 SCCP?). Moreover, the accuracy of various conventional histopathological parameters for predicting cancer-specific survival (CSS) in surgically treated SCCP has not been systematically evaluated yet. Based on the so far largest study cohort encompassing 158 consecutive patients with surgically treated PSCCs characterised by means of a central histopathological review, our data add the following to the currently available literature: (i) Ki-67, mini-chromosome maintenance 2 protein (MCM2), and geminin indicate a more aggressive behaviour in SCPP but do not represent independent prognostic parameters in the multivariable analysis in terms of CSS, (ii) these three biomarkers are not helpful for refining the delineation between different Broders' grading categories at the immunohistochemical level, and (iii) the conventional histopathological parameters staging, grading, nodal involvement, and lymphovascular invasion are independent prognostic parameters that together achieve a predictive accuracy of 82% for CSS. OBJECTIVE: To assess the role of cell proliferation-associated biomarkers to predict cancer-specific survival (CSS) in patients with surgically treated squamous cell carcinoma of the penis (SCCP). PATIENTS AND METHODS: A multicentre study enrolling 158 consecutive patients with surgically treated SCCP was performed. After conducting a central histopathological review, the staining profiles of Ki-67, mini-chromosome maintenance 2 protein (MCM2) and geminin were evaluated for their correlation with conventional histopathological criteria and their prognostic relevance for predicting CSS in a multivariable Cox proportional hazards regression model (median [interquartile range] follow-up 33 [6-63] months). RESULTS: Staining evaluation showed high interobserver agreement (92-96%). Ki-67 and MCM2 displayed a significant positive correlation with histological tumour grade, lymphovascular invasion (LVI) and nodal status, whereas geminin expression only correlated with tumour grade. The 5-year CSS for the entire study cohort was 62%. Univariable analysis showed a significant prognostic impact of Ki-67 (P = 0.026), MCM2 (P = 0.007), and geminin (P = 0.036). In multivariable analysis, only pT (hazard ratio [HR] 1.67; P = 0.003) and pN stage (HR 2.62; P = 0.015) as well as tumour grade (HR 1.89; P = 0.036) and LVI (HR 2.66; P = 0.028) were identified as independent prognostic parameters for CSS. The accuracy of the Cox model for CSS prediction was 0.820 (95% confidence interval 0.741-0.898). CONCLUSIONS: At present, conventional histopathological criteria remain the most powerful predictors of CSS in surgically treated SCCP. Due to overlapping staining profiles, Ki-67, MCM2 and geminin, either singly or in various combinations, failed to immunohistochemically refine the boundaries between Broders' grading categories. Ki-67, MCM2 and geminin do not represent independent prognostic parameters but reflect a more aggressive behaviour in surgically treated SCCP. Further studies are needed to clarify the currently contradictory predictive role of proliferation-associated biomarkers in terms of predicting nodal involvement in SCCPs.

Inherent grading characteristics of individual pathologists contribute to clinically and prognostically relevant interobserver discordance concerning Broders' grading of penile squamous cell carcinomas.

INTRODUCTION: We assessed the reproducibility and prognostic impact of the Broders' grading system (BGS) in a cohort of 147 patients with surgically treated penile squamous cell carcinomas. MATERIALS AND METHODS: Conventionally stained histology slides were graded according to the BGS in two rounds by two study pathologists. Reproducibility was assessed using ĸ statistics. Multivariable analyses were calculated to predict cancer-specific survival (CSS). The 'mean grade' per pathologist per round was calculated by allocating grade points to each study case (G1-G4: 1-4 points) and dividing the sum of all grade points by the number of cases examined. RESULTS: The BGS showed substantial interobserver variation (59-87% with ĸ = 0.38-0.69) but almost perfect intraobserver reproducibility (91% with ĸ = 0.86 and 96% with ĸ = 0.94, respectively). The 'mean grade' per pathologist remained nearly constant in both rounds of examination (differences ≤0.05 grade points) but differed between the two pathologists (up to 0.4 grade points). In multivariable analyses, the prognostic impact of the BGS in terms of CSS was strongly pathologist-dependent. CONCLUSIONS: Clinically and prognostically relevant interobserver discordance concerning the BGS seems, at least in part, to be attributable to inherent 'aggressive' versus 'reserved' grading characteristics of individual pathologists.

p16(INK4a) is a marker of good prognosis for primary invasive penile squamous cell carcinoma: a multi-institutional study.

PURPOSE: We assessed the prognostic role of p16(INK4a) expression in penile cancer with respect to cancer specific survival. MATERIALS AND METHODS: Based on a multi-institutional collaboration wax embedded tissues from 92 surgically treated patients, including 27 with total and 65 with partial penectomy, were retrospectively evaluated. After a central histopathological review by 1 pathologist a tissue microarray was constructed for p16(INK4a) immunostaining. Two independent pathologists evaluated p16(INK4a) expression, which was correlated with cancer specific survival. The κ statistic was used to assess interobserver variability. Univariate and multivariate Cox proportional hazards analysis was applied to assess the independent effects of prognostic factors on cancer specific survival during a median postoperative followup of 32 months (IQR 6-66). RESULTS: The κ statistic revealed excellent interobserver agreement (κ 0.934, p <0.001). Two and 5-year cancer specific survival rates for the entire study cohort were 86% and 74%, respectively. The 2 and 5-year rates for patients without and with p16(INK4a) expression differed significantly (73% and 57% vs 95% and 85%, respectively, p = 0.011). Univariate analysis revealed p16(INK4a) expression as a significant prognostic factor with respect to cancer specific survival (p = 0.018). Multivariate analysis identified koilocytosis (HR 0.24, 95% CI 0.07-0.83, p = 0.024), p16(INK4a) expression (HR 0.44, 95% CI 0.23-0.84, p = 0.013), and histological stage (HR 3.54, 95% CI 1.88-6.67, p <0.001) and grade (HR 2.47, 95% CI 1.00-6.09, p = 0.049) as independent prognostic factors for cancer specific survival. CONCLUSIONS: Results show that p16(INK4a) seems to be a prognostic parameter for primary invasive penile cancer with excellent interobserver reproducibility. At pathology laboratories without antibodies against p16(INK4a) conventional histological determination of koilocytosis by the pathologist also appears to provide important prognostic information for cancer specific survival.

Should we abstain from Gleason score 2-4 in the diagnosis of prostate cancer? Results of a German multicentre study.

PURPOSE: The present study analysed the loss of prognostic information related to the abandonment of Gleason score (GS) 2-4 by the International Society of Urological Pathology (ISUP-2005). METHODS: Within a 10-year period prior to the modification of GS, 856 patients (mean age 64.2 years) underwent radical prostatectomy (RP). The grade of agreement between GS in biopsy and definitive histology was calculated by Kappa statistics (κ). Univariable and multivariable influence of different preoperatively available parameters on disease-free survival (DFS) were assessed. The mean follow-up period was 39 months. RESULTS: Concordance between GS in biopsy versus RP samples was 58% (κ-value 0.354) and was improved by an increased number of biopsy cores. Undergrading in biopsy was present in 38% and not significantly enhanced by an extended time-period between biopsy and RP (threshold 90 d). PSA level, clinical tumour stage, fraction of positive cores (dichotomized at 34%), cases of RP per year and institution (dichotomized at 75), and GS independently influenced DFS. An upgrading to GS ≥ 7 was found in only 5.7% of patients presenting with GS 2-4 in the biopsy. Independent from definitive histology, patients with GS 2-4 had a significantly better prognosis compared to patients with a higher GS. CONCLUSIONS: The present study shows an independent prognostic impact of GS in biopsy samples classified according to the previous classification. The elimination of GS 2-4 by the ISUP 2005 results in a considerable loss of pretherapeutic prognostic information and therefore should be questioned in particular with regard to the increasing demand for active surveillance regimens.

Pathological upstaging detected in radical cystectomy procedures is associated with a significantly worse tumour-specific survival rate for patients with clinical T1 urothelial carcinoma of the urinary bladder.

OBJECTIVE: Due to their variable oncological course, clinical stage T1 (cT1) urothelial carcinomas of the bladder (UCBs) are the subject of controversial discussion with regard to indication for radical cystectomy (RC).This study aimed to evaluate the frequency and prognosis of upstaging in patients undergoing RC due to UCB. MATERIAL AND METHODS: Clinical and pathological records of 607 patients, having undergone RC for treatment of UCB in cT1N0M0, were summarized in a multi-institutional database. Cancer-specific survival (CSS) and overall survival (OS) rates were calculated. A multivariable prognostic model predicting the possibility of an upstaging in RC specimens was developed based on clinical information. RESULTS: In 210patients (35%) an upstaging (> pT1 and/or pN+) was detected in the RC specimen. Five-year CSS was 86%, 78%, 60%and 34%, respectively, for tumour stages < pT2N0 (n = 397), pT2N0 (n = 78), > pT2N0 (n = 63)and pN+ (n = 69) (p < 0.001). In a multivariable Cox regression model, pN stage, pT stage and lymphovascular invasion (LVI) revealed an independent influence on CSS (OS: pN, pT, age). An upstaging of cT1 tumours was enhanced by the criteria of G3 tumour grading and absent Tis in the transurethral resection of the bladder (TURB)specimen. Detection of LVI in RC specimens was also independently associated with an upstaging and, therefore, is recommended as a relevant prognostic parameter for the histopathological evaluation of TURB specimens. CONCLUSIONS: More than one-third of patients with cT1 tumours had an upstaging that was associated with significant prognosis deterioration. Further valid markers are required for an early identification of these patients. LVI represents such a criterion and, therefore, should be evaluated in prospectively designed trials with accurate histopathological assessment of TURB specimens.

Is radical oncosurgery justified for the treatment of primary malignant fibrous histiocytoma of the urinary bladder? Report of two cases and analyses of disease-specific survival rates based on a review of the literature.

Disease-specific survival (DSS) rates were evaluated in 20 patients with primary malignant fibrous histiocytoma (MFH) of the bladder. The most common pathologic finding was the pleomorphic subtype of MFH (55%) with a mean tumor size of 6.8 cm. 10 patients underwent surgery without and 6 patients with adjuvant therapy. Local and systemic rates of progression were 30 and 60% after surgery only compared with 16.7 and 50% after surgery with adjuvant therapy. Although none of the patients showed metastatic dissemination at the time of diagnosis, overall 1- and 2-year DSS rates of only 47.8 and 31.9% were observed. Hence, after the onset of clinical symptoms, the disease runs a very aggressive course regardless of the therapeutic options employed. Although distant dissemination seems to be rare at the time of diagnosis, the prognostic outcome is dismal. The rarity and inconsistency of the currently available case reports on MFH of the bladder hampers the development of therapeutic guidelines. Advanced studies enrolling a larger number of patients with appropriate clinical and pathological data are needed to compare the beneficial effects of various treatment options.

Urinary collecting system invasion reflects adverse long-term outcome and is associated with simultaneous metastatic spread at the time of surgery and with multilocular dissemination during postsurgical follow-up in renal cell cancer.

OBJECTIVES: To assess the prognostic implication of urinary collecting system invasion (CSI) in renal cell cancer (RCC). METHODS: Surveying a mean follow-up of 85 months, we investigated a cohort of 834 patients after radical (n = 710) or partial (n = 124) nephrectomy. At the time of surgery, 63 patients (7.6%) suffered from metastatic RCC. Various histopathologic parameters were analysed, and cancer specific survival (CSS) curves were individualized for each parameter. Furthermore, multivariate analysis was accomplished. RESULTS: Collecting system invasion was independently associated with a significant decline in CSS and was associated with simultaneous metastatic spread at the time of surgery and multilocular (involvement of at least two different organ systems) dissemination. CONCLUSIONS: The prognostic implication of CSI in RCC appears to be more complex than expected. Therefore, pathologists should report on CSI to enable selection of patients to be investigated in prospective studies which are needed to clarify the prognostic role of CSI in RCC.

Expression of prostatic acid phosphatase (PSAP) in transurethral resection specimens of the prostate is predictive of histopathologic tumor stage in subsequent radical prostatectomies.

Clinical management of incidental prostate cancer (IPC) remains challenging since its clinical course cannot be predicted by conventional histopathology. Aiming to define predictive factors in IPC, we correlated the immunohistochemically detected expression of prostate-specific antigen (PSA), prostatic acid phosphatase (PSAP), alpha-methylacyl-CoA racemase (AMACR, p504s), and androgen receptor in transurethral resection specimens with Gleason scores and histologic staging on the corresponding radicals in a cohort of 54 patients (mean age, 65.9 years; range, 49-80 years). PSAP expression showed a significant correlation with tumor staging (rho = -0.37; p = 0.02) but not with Gleason scores (rho = -0.06; p = 0.69). K-statistics revealed a highly significant moderate interobserver agreement concerning the evaluation of PSAP staining (K = 0.47; p < 0.001). In contrast, the other markers assessed failed to correlate with conventional histopathology. Therefore, PSAP might be predictive of tumor stage in IPC and represent a valuable adjunct for clinical decisions in terms of individual therapeutic management.

Expression of CD44s in incidental prostate cancer is more strongly associated with Gleason scores on subsequent radical prostatectomies than conventional prognostic parameters.

OBJECTIVE: Incidental prostate cancer (IPC) has a substantially variable clinical course which cannot be predicted by conventional histopathologic examination of transurethral resection specimens of the prostate (TURP chips). Therefore, efforts should be directed towards defining the natural history of individual IPC. Recently, expression of CD44s (standard isoform), a transmembranous glycoprotein, has been linked to prognostic outcome in prostate cancer, but its prognostic role in IPC has been neglected so far. METHODS: We present a multicentre study which evaluates immunohistochemically the largest cohort of IPC patients to date, aiming to correlate CD44s expression in the TURP chips with histopathologic outcome parameters (Gleason scores and histologic staging) performed on subsequent radical prostatectomies (RPs) in a cohort of 54 patients who underwent prostatectomy due to IPC. RESULTS: CD44s expression recorded in the TURP chips showed a stronger (inverse) association with Gleason scores performed on the corresponding RPs than did other conventional prognostic variables and, therefore, might become a valuable adjunct to better predict outcome in IPC prior to radical prostatectomy. CONCLUSION: Advanced prospective studies should aim to define cut-point values of CD44s expression for separating aggressive tumours from their indolent counterparts, and should also assess possible associations with clinical follow-up data (e.g. progression-free survival) in IPC.

The FUSE binding proteins FBP1 and FBP3 are potential c-myc regulators in renal, but not in prostate and bladder cancer.

BACKGROUND: The three far-upstream element (FUSE) binding proteins (FBP1, FBP2, and FBP3) belong to an ancient family of single-stranded DNA binding proteins which are required for proper regulation of the c-myc proto-oncogene. Whereas it is known that c-myc alterations play a completely different role in various carcinomas of the urogenital tract, the relevance of FBPs is unclear. METHODS: FBP1, FBP3 and c-myc expression was studied in 105 renal cell, 95 prostate and 112 urinary bladder carcinomas by immunohistochemistry using tissue microarrays. RESULTS: High rates of FBP1 and FBP3 expression were observed in all cancer types. There was a concomitant up-regulation of FBP1 and FBP3 in renal cell and prostate carcinomas (p < 0.001 both). C-myc expression was detectable in 21% of prostate, 30% of renal and 34% of urothelial carcinomas. Interestingly, strong FBP1 and FBP3 expression was associated with c-myc up-regulation in clear cell renal cell carcinomas (p < 0.001 and 0.09 resp.), but not in bladder or prostate cancer. CONCLUSION: The correlation between FBP1/FBP3, c-myc and high proliferation rate in renal cell carcinoma provides strong in vivo support for the suggested role of FBP1 and FBP3 as activators of c-myc. The frequent up-regulation of FBP1 and FBP3 in urothelial and prostate carcinoma suggests that FBPs also have an important function in gene regulation of these tumors.

Expression of alpha-methylacyl-CoA racemase correlates with histopathologic grading in noninvasive bladder cancer.

Alpha-methylacyl-CoA racemase (AMACR, p504S), an enzyme involved in cellular energy metabolism by the oxidation of branched-chain fatty acids, is a biomarker that is known to be overexpressed in prostatic and colorectal carcinoma as well as in papillary renal cell carcinoma. We aimed to correlate its immunohistochemically detected expression with histopathological grading in noninvasive bladder cancer in order to hint at a so far unknown role of AMACR in the pathobiology of this tumor entity. Therefore, a cohort of 163 patients (mean age 65.3 years) diagnosed with noninvasive bladder cancer was immunohistochemically investigated in terms of AMACR expression. There was variable positive AMACR staining in 52 (31.9%) of the cases investigated. All tumors were graded by three independent clinical histopathologists according to the 1973 World Health Organization (WHO) and the 1998 WHO/International Society of Urological Pathology (ISUP) system. We found a significant positive correlation between AMACR expression and higher tumor grades using both histopathologic grading schemes. These novel findings clearly allow including high-grade noninvasive bladder carcinomas in the group of AMACR-positive neoplasms and might reflect a so far unknown role of AMACR racemase in the pathobiology and tumor cell energy metabolism of the latter tumor entity.

Complications and risk factors of transrectal ultrasound guided needle biopsies of the prostate evaluated by questionnaire.

BACKGROUND: Transrectal ultrasound guided prostate needle biopsies are routinely performed to diagnose and stage prostate cancer. We prospectively evaluated the safety, morbidity, and complication rate. MATERIALS AND METHODS: We studied 336 patients who underwent transrectal ultrasound guided prostate needle biopsy. A post-biopsy questionnaire was sent to the patients 4 weeks after biopsy concerning questions about minor complications. Information on major complications was obtained by telephone interview. RESULTS: There were 2 major and 48 minor complications. The most common complication was hematuria in 6.5% of cases, followed by pain while urinating in 6.0% of cases. There was no statistically significance difference between hematuria and aspirin/thrombolytic drug use (P = 0.170) and between positive microbiology in urine and elevated temperature (P = 0.665). CONCLUSIONS: Transrectal ultrasound guided prostate needle biopsy is safe for diagnosing prostate cancer with few major and minor complications. Aspirin/thrombolytic drug use in patients' history is no risk factor for hematuria. Positive microbiology in urine before biopsy is no risk factor for a higher infection rate.

Body mass index (BMI) and mutations of tumor suppressor gene p53 (TP53) in patients with urinary bladder cancer.

OBJECTIVE: Obesity is estimated to account for up to 20% of all cancer deaths. Mutations of TP53 are frequently correlated with tumor development and progression. We evaluated the effect of body mass index (BMI) and mutation status of tumor suppressor gene p53 (TP53) on patients with urinary bladder cancer. MATERIALS AND METHODS: Clinical samples were used from 75 patients with tumors of the urinary bladder. Mutation status in TP53 exons 5, 6, 7, and 8 was analyzed by temperature gradient gel electrophoresis of exon-specific PCR products and by sequence analysis. Statistical analysis included Pearson's correlation. RESULTS: For noninvasive bladder cancer, the mutation frequency in TP53 was 44.6%, while for invasive bladder cancer the mutation frequency in TP53 was 84.2%. Normal weight, overweight, and patients with obesity had a TP53 mutation frequency of 68.4%, 44.8%, and 25%, respectively (P < 0.05). CONCLUSIONS: TP53 mutation frequently occurs in higher stages of bladder tumors. Body mass index is not associated with a higher TP53 mutation frequency in our study, but BMI should be included for collecting data of bladder cancer risk profile.

Penile entrapment in a plastic bottle - a case for using an oscillating splint saw.

Penile entrapment is a rare but serious urological emergency, which can easily lead to stangulation and infarction. We report a case of penile entrapment in a polyethylene terephthalate (PET) bottle in a 49-year-old male. Attempts to cut the bottle with a scalpel or a glass saw were ineffective. Finally, the bottle neck was cut longitudinally with an oscillating saw intended for cutting plaster casts.

The white pulp in the setting of the septic spleen caused by different bacteria: a comparative morphometric study.

In the past little attention has been paid to histomorphologic changes accompanying the phenomenon of the septic spleen, thus indirectly reinforcing the old axiom that the spleen is an organ of mystery. It is especially noteworthy that the relationship between different causative bacteria and histopathologic abnormalities of the white pulp has not been investigated. In this study morphometric analysis was performed on the white pulp of 30 spleens obtained at autopsy from individuals with premortal sepsis. A strictly defined age- and sex-matched control group was analyzed for statistical comparison. Our findings demonstrate a significant depletion of B- and T-areas in the septic spleen, accompanied by a significant tendency towards reactive germinal center hyperplasia regardless of the type of bacteria responsible. However, depletion of splenic B-areas was shown to be significantly pronounced in the setting of premortal enterococcemia in comparison with a panel of gram-negative flagellated bacteria. It is felt that certain bacterial virulence factors (e.g. flagellation and/or structural components of the cell wall) might be pathogenetically involved in the observed changes, reflecting a partially different activation of splenic lymphocytes in the setting of the septic spleen.

Intrauterine torsion of a testicular teratoma: a case report.

Neonatal testicular tumors and intrauterine testicular torsions are very rare. The presented case is the first describing intrauterine torsion of a descended testis with a teratomatous tumor. Immediately after birth, right hemiscrotal swelling was seen in a preterm male newborn. Surgical intervention showed extravaginal testicular torsion and a highly differentiated testicular teratoma with haemorrhagic infarction. The testis was removed (orchiectomy). Over a period of twelve months no signs of tumor recurrence were found. While being extremely rare, testicular tumors should be included in the differential diagnosis of neonatal scrotal swelling.

Evaluation of the prognostic significance of perirenal fat invasion and tumor size in patients with pT1-pT3a localized renal cell carcinoma in a comprehensive multicenter study of the CORONA project. Can we improve prognostic discrimination for patients with stage pT3a tumors?

BACKGROUND: The current TNM system for renal cell carcinoma (RCC) merges perirenal fat invasion (PFI) and renal vein invasion (RVI) as stage pT3a despite limited evidence concerning their prognostic equivalence. In addition, the prognostic value of PFI compared to pT1-pT2 tumors remains controversial. OBJECTIVE: To analyze the prognostic significance of PFI, RVI, and tumor size in pT1-pT3a RCC. DESIGN, SETTING, AND PARTICIPANTS: Data for 7384 pT1a-pT3a RCC patients were pooled from 12 centers. Patients were grouped according to stages and PFI/RVI presence as follows: pT1-2N0M0 (n=6137; 83.1%), pT3aN0M0 + PFI (n=1036; 14%), and pT3aN0M0 (RVI ± PFI; n=211; 2.9%). INTERVENTION: Radical nephrectomy or nephron-sparing surgery (NSS) (1992-2010). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cancer-specific survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional-hazards regression models, as well as sensitivity and discrimination analyses, were used to evaluate the impact of clinicopathologic parameters on cancer-specific mortality (CSM). RESULTS AND LIMITATIONS: Compared to stage pT1-2, patients with stage pT3a RCC were significantly more often male (59.4% vs 53.1%) and older (64.9 vs 62.1 yr), more often had clear cell RCC (85.2% vs 77.7%), Fuhrman grade 3-4 (29.4% vs 13.4%), and tumor size >7 cm (39.1% vs 13%), and underwent NSS less often (7.5% vs 36.6%; all p<0.001). According to multivariate analysis, CSM was significantly higher for the PFI and RVI ± PFI groups compared to pT1-2 patients (hazard ratio [HR] 1.94 and 2.12, respectively; p<0.001), whereas patients with PFI only and RVI ± PFI did not differ (HR 1.17; p=0.316). Tumor size instead enhanced CSM by 7% per cm in stage pT3a (HR 1.07; p<0.001) with a 7 cm cutoff yielding the highest prediction accuracy. CONCLUSIONS: Since the prognostic impact of PFI and RVI on CSM seems to be comparable, merging both as stage pT3a RCC might be justified. Enhanced prognostic discrimination of stage pT3a RCC appears to be possible by applying a tumor size cutoff of 7 cm within an alternative staging system. PATIENT SUMMARY: Prognosis prediction for patients with localized renal cell carcinoma up to stage pT3a can be enhanced by including tumor size with a cutoff of 7 cm as an additional parameter in the TNM classification system.

FISH--a new noninvasive method for the diagnosis of urinary bladder carcinomas.

Urinary bladder carcinoma is one of the most frequent malignant tumour diseases. The frequency increases with advancing age. The knowledge increase about genetic changes in tumour cells opens the possibility of a new noninvasive diagnosis with the help of fluorescence in situ hybridization (FISH). Comparable data are obtained by application of different diagnostic methods (fluorescence in situ hybridization, urinary bladder cancer ELISA, urinary cytology, histopathology) at different times from 6 coincidentally selected patients (preoperation, biopsy material and postoperation). The FISH test proved to be a sensitive method and correlated with the histopathological data.

Does the width of the surgical margin of safety or premalignant dermatoses at the negative surgical margin affect outcome in surgically treated penile cancer?

AIMS: To evaluate the prognostic impact of the width of negative surgical margins (NSM) and associated and preinvasive lesions at the NSM in patients with penile squamous cell cancer (PSC). METHODS: Enrolling 87 patients with NSM who underwent surgery for PSC, the archived margin slides and entirely wax-embedded surgical margins were retrieved from the pathology files. After step sections were cut, margins were stained with antibodies against CK5/6, p16, p53 and Ki-67 and subjected to in situ hybridisation for high-risk human papillomavirus (HPV). All NSM were histologically examined for squamous hyperplasia (SH), lichen sclerosus (LS) and subtypes of penile intraepithelial neoplasia (PeIN). Then, histological findings were correlated with cancer-specific mortality (CSM, median follow-up 34 months; IQR 6-70). RESULTS: All NSM were negative for high-risk HPV and exhibited SH (p16 and p53 negative, Ki-67 variably positive), LS (p16 negative, variable p53 and Ki-67 positivity) and differentiated PeIN (dPeIN; p16 negative, Ki-67 positive, variable p53 positivity) in 28 (32%), 30 (34%) and 22 (25%) cases, respectively, whereas PeIN subtypes other then dPeIN did not occur. Pathological tumour stage was the only independent predictive parameter with respect to CSM in the multivariable analysis (p=0.001). CONCLUSIONS: SH, LS and dPeIN are frequent histological findings at the NSM of surgically treated PSC. However, neither the width of the NSM nor dPeIN, LS or SH at the NSM influences prognostic outcome.