Gregor Mikuz

Testicular Torsion: Late Results with Special Regard to Fertility and Endocrine Function

Late results were determined for 42 patients who had undergone detorsion and fixation for unilateral testicular torsion in the prepubertal and pubertal age. Exocrine and endocrine function for the testes was determined in 30 patients who had reached postpuberal age. Patients who underwent detorsion and fixation 8 hours or less after the onset of symptoms had normal-sized testicles and only slight changes in testicular morphology. When treatment was delayed and detorsion was done more than 8 hours later a marked decrease was observed in testicular size. The exocrine function in patients with torsion was reduced. The semen quality, as judged by 2 semen analyses, was normal in 15 patients, doubtful in 3 and pathological in 12. Even when detorsion was done 4 hours or less after the onset of symptoms the exocrine function of the testes was normal in only 50 per cent of the cases. In patients with doubtful and pathological sperm analyses higher follicle-stimulating and luteinizing hormone levels were observed.

Ep-CAM overexpression in breast cancer as a predictor of survival

The epithelial glycoprotein Ep-CAM is overexpressed in colon cancer and breast cancer. We assessed the frequency and prognostic significance of Ep-CAM in tissue specimens from 205 patients with invasive breast cancer, by immunohistochemical staining with a monoclonal antibody specific for the Ep-CAM antigen. Ep-CAM overexpression was found in 35.6% of samples and was associated with poor disease-free and overall survival.

Prognostic factors and reporting of prostate carcinoma in radical prostatectomy and pelvic lymphadenectomy specimens

This paper, based on the activity of the Morphology-Based Prognostic Factors Committee of the 2004 World Health Organization-sponsored International Consultation, describes various methods of handling radical prostatectomy specimens for both routine clinical use and research purposes. The correlation between radical prostatectomy findings and postoperative failure is discussed in detail. This includes issues relating to pelvic lymph node involvement, detected both at the time of frozen section and in permanent sections. Issues of seminal vesicle invasion, including its definition, routes of invasion and relationship to prognosis, are covered in detail. The definition, terminology and incidence of extra-prostatic extension are elucidated, along with its prognostic significance relating to location and extent. Margins of resection are covered in terms of their definition, the etiology, incidence and sites of positive margins, the use of frozen sections to assess the margins and the relationship between margin positivity and prognosis. Issues relating to grade within the radical prostatectomy specimen are covered in depth, including novel ways of reporting Gleason grade and the concept of tertiary Gleason patterns. Tumor volume, tumor location, vascular invasion and perineural invasion are the final variables discussed relating to the prognosis of radical prostatectomy specimens. The use of multivariate analysis to predict progression is discussed, together with proposed modifications to the TNM system. Finally, biomarkers to predict progression following radical prostatectomy are described, including DNA ploidy, microvessel density, Ki-67, neuroendocrine differentiation, p53, p21, p27, Bcl-2, Her-2/neu, E-cadherin, CD44, retinoblastoma proteins, apoptotic index, androgen receptor status, expression of prostate-specific antigen and prostatic-specific acid phosphatase and nuclear morphometry.

Prognostic and predictive factors and reporting of prostate carcinoma in prostate needle biopsy specimens

The information provided in the surgical pathology report of a prostate needle biopsy of carcinoma has become critical in the subsequent management and prognostication of the cancer. The surgical pathology report should thus be comprehensive and yet succinct in providing relevant information consistently to urologists, radiation oncologists and oncologists and, thereby, to the patient. This paper reflects the current recommendations of the 2004 World Health Organization-sponsored International Consultation, which was co-sponsored by the College of American Pathologists. It builds on the existing work of several organizations, including the College of American Pathologists, the Association of Directors of Anatomic and Surgical Pathologists, the Royal Society of Pathologists, the European Society of Urologic Pathology and the European Randomized Study of Screening for Prostate Cancer.

Prognostic significance of Ep-CAM AND Her-2/neu overexpression in invasive breast cancer.

To assess the frequency and prognostic impact of Ep‐CAM and Her‐2/neu overexpression in patients with breast cancer and to determine its relationship with other prognostic markers, 205 breast cancer patients with a median follow‐up of 10.8 years were enrolled in this retrospective study. Overexpression of Ep‐CAM and Her‐2/neu in tumor tissue samples was assessed by immunohistochemistry. Tumors presenting a Her‐2/neu 2+ staining were additionally analyzed by FISH to exclude false positive results. Ep‐CAM and Her‐2/neu overexpression was found in 35.6% and 19.5% of the tumor samples, respectively. Both Ep‐CAM and Her‐2/neu overexpression were predictive for poor disease‐free (DFS) and disease‐related overall survival (DROS). Concurrent Ep‐CAM and Her‐2/neu overexpression was present in 13.2% of tumor specimens and had an additive negative impact on DFS and DROS. This minority of patients had a median time to relapse of only 34 months, whereas the median time to relapse was not reached in the patient population without Her‐2/neu and Ep‐CAM overexpression. By multivariate analysis Ep‐CAM overexpression proved to be an indicator of poor prognosis, independent of tumor size, histologic grade, hormone receptor expression and Her‐2/neu overexpression. In conclusion, overexpression of Ep‐CAM and Her‐2/neu complement each other as predictors for poor prognosis in patients with invasive breast cancer. Determination of these tumor markers should help in assigning breast cancer patients to 1 of 3 distinct risk categories.

A working group classification of focal prostate atrophy lesions

Focal atrophy is extremely common in prostate specimens. Although there are distinct histologic variants, the terminology is currently nonstandardized and no formal classification has been tested for interobserver reliability. This lack of standardization hampers the ability to study the biologic and clinical significance of these lesions. After informal and formal meetings by a number of the authors, focal atrophy lesions were categorized into 4 distinct subtypes as follows: (i) simple atrophy, (ii) simple atrophy with cyst formation, (iii) postatrophic hyperplasia, and (iv) partial atrophy. In phase 1 of the study, pathologists with varying levels of experience in prostate pathology were invited to view via the Internet a set of “training” images with associated descriptions of lesions considered typical of each subtype. In phase 2 of the study, each participant provided diagnoses on a series of 140 distinct “test” images that were viewed over the Internet. These test images consisted of the 4 subtypes of atrophy and images of normal epithelium, high grade prostatic intraepithelial neoplasia, and carcinoma. The diagnoses for each image from each pathologist were compared with a set of “standard” diagnoses and the κ statistic was computed. Thirty-four pathologists completed both phases of the study. The interobserver reliability (median κ) for classification of lesions as normal, cancer, prostatic intraepithelial neoplasia, or focal atrophy was 0.97. The median κ for the classification of atrophy lesions into the 4 subtypes was 0.80. The median percent agreement with the standard diagnosis for the atrophy subtypes were: simple 60.6%, simple with cyst formation 100%; postatrophic hyperplasia 87.5%; partial atrophy 93.9%. The lower percentage for simple atrophy reflected a propensity to diagnose some of these as simple atrophy with cyst formation. Seven pathologists completed the phase 2 analysis a second time, and their intraobserver reproducibility was excellent. Three of 4 pathologists with low agreement with the standard diagnosis for simple atrophy improved their scores after repeating the analysis after re-examination of the “training set” of images. In conclusion, these criteria for variants of focal prostate atrophy may facilitate studies to examine the relation between various patterns of prostate atrophy and prostate cancer.

Detection and clinical outcome of urinary bladder cancer with 5-aminolevulinic acid-induced fluorescence cystoscopy : A multicenter randomized, double-blind, placebo-controlled trial.

The medical community lacks results from prospective controlled multicenter studies of the diagnostic efficacy of 5‐aminolevulinic acid (5‐ALA) cystoscopy on tumor recurrence in patients with superficial bladder tumors.

Value of Real-Time Elastography Targeted Biopsy for Prostate Cancer Detection in Men With Prostate Specific Antigen 1.25 ng/ml or Greater and 4.00 ng/ml or Less

PURPOSE We assessed the prostate cancer detection rate of real-time elastography targeted biopsy in men with total prostate specific antigen 1.25 ng/ml or greater and 4.00 ng/ml or less. MATERIALS AND METHODS Real-time elastography using an EUB 8500 Hitachi ultrasound system (Hitachi Medical, Tokyo, Japan) was done in 94 men with a mean age of 57.4 years (range 35 to 77) with increased prostate specific antigen between 1.25 ng/ml or greater and 4.00 ng/ml or less (mean 3.20, range 1.30 to 4.00) and a free-to-total prostate specific antigen ratio of less than 18%. Real-time elastography was done to evaluate peripheral zone tissue elasticity and hard areas were defined as suspicious. Targeted biopsies with a maximum of 5 cores were done in suspicious areas, followed by 10-core systematic biopsy. We analyzed the cancer detection rate of real-time elastography and systematic biopsy. RESULTS Cancer was found in 27 of 94 patients (28.7%). Real-time elastography detected cancer in 20 patients (21.3%) and systematic biopsy detected it in 18 (19.1%). Positive cancer cores were found in real-time elastography targeted cores in 38 of 158 cases (24%) and in systematic cores in 38 of 752 (5.1%) (chi-square test p <0.0001). The cancer detection rate per core was 4.7-fold greater for targeted than for systematic biopsy. CONCLUSIONS Real-time elastography targeted biopsy allows prostate cancer detection in men with prostate specific antigen 1.25 ng/ml or greater and 4 ng/ml or less with a decreased number of cores compared with that of systematic biopsy.

CD30 expression in seminoma

In testicular germ cell tumors the CD30 antigen has been shown to be regularly expressed in embryonal carcinoma and was thus suggested as a marker for this particular neoplasm. Very recently, it has been proven that the monoclonal antibody Ber-H2 is suitable for the detection of this membrane antigen in paraffin sections. We conducted an immunohistochemical study to investigate the CD30 expression in a large series of different presentations of seminoma (ie, pure, mixed, and spermatocytic) because there is evidence from several sources that embryonal carcinoma is histogenetically closely related to, and probably derives from, seminoma. Sections from formalin-fixed, paraffin-embedded tissue from 38 cases of testicular seminomas were immunostained for the demonstration of the CD30 antigen using the monoclonal antibody Ber-H2, cytokeratins, and placental alkaline phosphatase following an indirect streptavidin-peroxidase regimen. In selected cases, immunostainings were performed on consecutive sections to investigate a possible colocalization of CD30 and cytokeratins in seminoma. Specific immunostaining for CD30 in seminoma cells could be detected in single minute foci in 4 of 21 cases of pure classic seminoma. Seminomatous components of mixed tumors showed CD30 positivity in single, but also multiple, foci in 7 of 14 cases. CD30 immunoreactivity in seminoma cells occurred with and without colocalized expression of cytokeratin. Spermatocytic seminoma (n = 3) as well as intratubular germ cell neoplasia in tumor adjacent parenchyma (n = 36) were negative in all cases investigated. We conclude that in testicular germ cell tumors, the expression of CD30 is not restricted to embryonal carcinoma but can also be found focally in seminoma, adding further evidence for a close relationship between these two tumors. The prevalence of CD30 expression in seminomatous components of mixed tumors, as well as the coexpression with cytokeratins, suggest that CD30 expression in seminomas might indicate their upcoming transformation to embryonal carcinoma. This conclusion coincides with a model featuring seminoma in a central role of germ cell tumor development.

Contrast‐enhanced ultrasonography using cadence‐contrast pulse sequencing technology for targeted biopsy of the prostate

To evaluate contrast‐enhanced ultrasonography (US) using cadence‐contrast pulse sequencing (CPS) technology, compared with systematic biopsy for detecting prostate cancer, as grey‐scale US has low sensitivity and specificity for detecting prostate cancer.