Maria Shevchuk

The Effect of Finasteride on the Expression of Vascular Endothelial Growth Factor and Microvessel Density: A Possible Mechanism for Decreased Prostatic Bleeding in Treated Patients

PURPOSE Several studies have confirmed the benefit of finasteride in limiting hematuria from benign prostatic hyperplasia. Vascular endothelial growth factor (VEGF), a potent stimulator of angiogenesis, and microvessel density have been independently evaluated in the mechanism of decreased bleeding observed in patients treated with finasteride. We evaluated the expression of VEGF and suburethral prostatic microvessel density in patients with benign prostatic hyperplasia treated with finasteride. MATERIALS AND METHODS The study included 24 patients undergoing prostatic surgery for benign disease, of whom 12 were given finasteride for a minimum of 6 weeks before surgery and the remaining 12 served as controls. Sections from the prostatic urothelium and hyperplastic prostate were individually stained for CD34 specific for nascent blood vessels and VEGF. Analysis of each specimen was performed in a blinded fashion. Microvessel density was calculated by counting the number of positively stained blood vessels on 10 consecutive, nonoverlapping, high power fields within the suburethral and hyperplastic prostate compartments. VEGF expression was examined by immunohistochemistry. Statistical analysis of the results was performed using Students t test. RESULTS Prostatic suburethral VEGF expression and microvessel density were significantly lower in the finasteride group compared to controls (p <0.05). Differences in VEGF expression and microvessel density at the level of the hyperplastic prostate were not found to be significantly different between the 2 groups. CONCLUSIONS Decreased expression of VEGF by finasteride inhibits angiogenesis and significantly decreases microvessel density in prostatic suburethral tissue. This sequential relationship provides histochemical insight into the mechanism by which finasteride reduces prostatic urethral bleeding.

Decreased Suburethral Prostatic Microvessel Density In Finasteride Treated Prostates: A Possible Mechanism For Reduced Bleeding In Benign Prostatic Hyperplasia

PURPOSE We evaluated the influence of finasteride on prostatic microvessel density to elucidate a mechanism of decreased bleeding in finasteride treated patients with hematuria secondary to benign prostatic hyperplasia (BPH). MATERIALS AND METHODS A total of 22 patients with clinical BPH and gross hematuria who underwent prostate reductive surgery between 1998 and 2000 were prospectively evaluated. The prostate from 10 finasteride treated and 12 untreated patients was immunohistochemically stained for CD-34. Microvessel density analysis was performed by quantifying positive stained blood vessels located within the stroma of hyperplastic nodules as well as in the suburethral portion of the prostate. RESULTS Mean microvessel density plus or minus standard deviation in finasteride treated patients was significantly lower in the suburethral portion of the prostate versus untreated controls (14.0 +/- 2.8 versus 20.2 +/- 5.3 vessels per high power field, p <0.05). In the nodular hyperplasia there was no statistically significant difference in the treatment and control groups (mean 17.5 +/- 2.8 and 16.7 +/- 4.6 vessels per high power field, respectively). CONCLUSIONS Finasteride significantly decreases suburethral prostatic microvessel density in patients with BPH, which may explain its efficacy for decreasing BPH associated bleeding.

HIV in testis: quantitative histology and HIV localization in germ cells

The testes of AIDS patients invariably show decreased spermatogenesis and are atrophic. These testicular changes can be grouped into three categories: (1) spermatogenesis present, but decreased; (2) spermatogenic arrest at primary spermatocyte stage; and (3) Sertoli only (or almost Sertoli only). The purpose of this study is 2-fold: firstly, to quantitate the numbers and types of germ cells in these three groups as compared with normals. In addition the presence of HIV-1 DNA positive germ cells was quantitated by PCR in situ hybridization. HIV-1 was identified in 14 of 15 testes from HIV infected adults, and was present in 25-33% of residual germ cells. There was an average of 18.9 HIV infected germs cells/tubule in the spermatogenesis group, 6.3 HIV infected germs cells in the spermatogenic arrest group, and 0.25 HIV infected germ cells in the almost Sertoli only group. HIV-1 DNA was absent in three of the three preadolescent boys testes (HIV acquired in utero). This study quantitates the degree of germ cell loss in AIDS patients and quantitates the degree of HIV positivity of the residual germ cells, thus shedding more light on the testicular HIV burden, with its possible repercussions for sexual transmission of HIV.

Changing testicular histology in AIDS: its implication for sexual transmission of HIV

OBJECTIVES The understanding of testicular histology in acquired immunodeficiency syndrome (AIDS) is essential, because the sexual route is one of the main means of transmission of the human immunodeficiency virus, which is localized primarily in the germ cells of the testes. It is important to determine whether any changes have occurred in the testicular histologic patterns in the course of the AIDS epidemic. METHODS One hundred forty testicular specimens were available from AIDS autopsies during the AIDS epidemic (1981 to 1998). The epidemic was divided into pre-zidovudine (pre-AZT) therapy (1981 to 1987) and antiviral therapy (1988 to 1998) periods; the latter period was further subdivided on the basis of the particular treatment used. Testicular histology was evaluated and correlated with patient age, CD4 T-cell counts, and pathologic findings in other parts of the body. RESULTS Testicular histologic findings were categorized into three groups: hypospermatogenesis (group S), spermatogenic arrest (group A), and Sertoli cell only (group O). The percentage of AIDS patients with group S histologic findings remained constant throughout the study period: 26% in the pre-AZT and 28% in the antiviral therapy periods. However, there was a reversal in the percentages of patients in groups A and O: group A decreased from 48% (pre-AZT) to 28% (antiviral) and group O increased from 26% (pre-AZT) to 44% (antiviral). There was no correlation between testicular histologic results and patient age or CD4 count. Opportunistic infections and testicular neoplasms were also identified. CONCLUSIONS This study demonstrates that current therapy and prolongation of survival in AIDS patients are associated with a shift in the histologic findings of testes toward a more pronounced loss of germ cells. However, 28% of patients still show significant spermatogenesis at the time of death from AIDS and this subgroup cannot be identified by age or CD4 T-cell counts. The presence of large numbers of residual germ cells in these patients suggests that they may continue to be infectious throughout their disease course.

Association Between Chlamydia trachomatis and Abnormal Uterine Bleeding

The purpose was to identify distinct inflammatory markers in endometrial tissues of women with abnormal uterine bleeding (AUB) and Chlamydia trachomatis infection.

Multiphoton microscopy: a potential intraoperative tool for the detection of carcinoma in situ in human bladder.

CONTEXT Urothelial carcinoma in situ (CIS) is a precursor of invasive bladder cancer, which if left untreated, will likely progress to more aggressive disease. Approximately 50% of CIS lesions are missed on routine cystoscopy owing to their flat architecture. Furthermore, many benign but abnormal-appearing areas may be biopsied owing to lack of cellular resolution of cystoscopes. Multiphoton microscopy (MPM) is an optical imaging technique that generates subcellular-resolution three-dimensional images from unfixed tissue without using exogenous dyes. OBJECTIVE To assess the diagnostic potential of MPM in identifying and differentiating benign from malignant flat bladder lesions, especially CIS. DESIGN Seventy-eight specimens (benign = 46, CIS = 23, invasive = 9, as diagnosed on histopathology) were obtained from flat bladder mucosa via transurethral resection of bladder, cold cup biopsy, or cystectomy, imaged fresh with a commercial benchtop MPM, and submitted for routine histopathology. Multiphoton microscopy and hematoxylin-eosin diagnoses were compared. RESULTS In 77 of 78 specimens (99%), accurate MPM diagnoses (benign/malignant) were given on the basis of their architectural and cytologic features (nuclear to cytoplasmic ratio, pleomorphism, polarity/organization of urothelial layers, etc). The sensitivity and specificity were 97% and 100%, respectively, with positive (malignant) and negative (benign) predictive values of 100% and 98%, respectively. The interobserver agreement, κ, was 0.93. CONCLUSIONS Our study demonstrates the capability of MPM to identify and differentiate benign from malignant flat bladder lesions, especially CIS. With the advent of MPM endoscopes, we foresee their potential as a biopsy guidance tool for early detection and treatment of CIS, thus reducing the rate of biopsies with benign diagnoses and their associated complications.

Proliferative extensor tenosynovitis of the wrist in the absence of rheumatoid arthritis.

PURPOSE Proliferative tenosynovitis in the fourth extensor compartment is common in patients with rheumatoid arthritis. It may also occur in the absence of rheumatoid arthritis; the purpose of this study is to describe this clinical condition in a series of patients, to report the results of surgical intervention, and to compare histological findings to those typically seen in rheumatoid tenosynovitis. METHODS This study presents a retrospective case series of 11 patients who do not have rheumatoid arthritis, who had proliferative tenosynovitis of the fourth extensor compartment treated surgically. Relevant features of the clinical presentation, physical examination, radiographic findings, and results of attempts at conservative treatment are described. Surgical pathology specimens were reviewed by a single pathologist to define common histological features and to compare the histology to that which is classically seen in rheumatoid tenosynovitis. RESULTS All patients presented with a painful wrist mass over the fourth extensor compartment. Characteristic in physical examination was severe limitation of active wrist extension with the fingers extended, with improvement when the fingers were flexed into a fist. After tenosynovectomy, wrist extension and grip strength improved. Examination of the surgical pathology specimens revealed a spectrum of pathological findings generally consistent with traumatic tenosynovitis, but a few specimens had rheumatoid-like features. CONCLUSIONS A review of this case series of patients with tenosynovitis but without rheumatoid arthritis demonstrates a distinct clinical condition of exuberant proliferative extensor tenosynovitis blocking proximal tendon excursion, thereby causing pain and limited active wrist extension, as well as a less distinct histological condition with a constellation of findings generally resembling traumatic tenosynovitis. In this group of patients, surgical tenosynovectomy generally yields excellent results. TYPE OF STUDY/LEVEL OF EVIDENCE Therapeutic IV.

Immunopathology of tissue markers in prostate cancer

SummaryProstatic acid phosphatase (PAP) and prostate specific antigen (PSA) are markers for tumors of prostatic origin. The immunoperoxidase staining for these substances is described for both benign prostates and prostatic carcinomas, including several less frequent subtypes. A list is presented of several non prostatic tissues, which can occassionally cross-react with antibodies to PAP and PSA. PSA is found to be the antigen of choice with PAP a valuable adjunct in differential diagnosis of difficult bladder neck lesions and of metastatic tumors. The usefulness of these markers in diagnosis of fine needle aspiration cytology is also examined.

The Effect of BCG on Angiogenesis and Cellular Proliferation in Recurrent Superficial TCC of the Bladder

Purpose: Tumor-associated angiogenesis and increased cellular proliferation in superficial transitional cell carcinoma (TCC) of the bladder represent promising new therapeutic targets, and have emerged as important prognostic indicators for cancer treatment. To our knowledge, these factors have not been studied in recurrent superficial TCC specimens treated with Bacillus Calmette-Guerin (BCG). The purpose of our study was to investigate the clinicopathologic response of BCG instillation on microvessel density (MVD) and cellular proliferation in recurrent superficial TCC of the bladder. Materials and methods: A total of 20 specimens from 10 patients were analyzed: 10 before (control group) and 10 after (treatment group) a 6 week instillation of BCG. In all specimens, tumor grade, MVD and cellular proliferation were analyzed in a blinded fashion. MVD was calculated by counting the number of blood vessels in the superficial lamina propria per high-power field. Immunohistochemistry was used to assess the expr...

Pilot study on the correlation of multiphoton microscopy of human testicular tumors with histology.

338 Background: Partial orchiectomy is becoming more accepted for indications such as a solitary testis, and small nonpalpable testicular masses found incidentally on scrotal ultrasonography. Unfortunately, intraoperative frozen-section pathological analysis is often unable to accurately predict the presence of malignancy. Multiphoton microscopy (MPM) enables in vivo imaging of tissue without the use of labeling techniques and could potentially diagnose testicular tumor pathology. We performed a non-randomized, non-controlled study to evaluate the feasibility of MPM to image testicular biopsies. METHODS Two men with testicular masses underwent radical orchiectomy for primary testicular tumor from June to August 2011. A total of six specimens from testicular tumor and uninvolved testes were imaged with MPM. In order to assess the diagnostic accuracy of MPM, we performed a blinded assessment by three uropathologists. The diagnosis rendered based on these images was then correlated with the findings seen on hematoxylin and eosin (H&E) staining. RESULTS Our diagnosis based on MPM correlated with H&E in five of six (83%) specimens. Images of seminoma acquired with the MPM are easily distinguished from those of teratoma and normal testicular parenchyma. Images of seminoma show abnormal architectural and cellular changes compared to cystic structures often seen with teratoma. CONCLUSIONS Multiphoton microscopy can be used to reliably differentiate between teratoma, seminoma and normal testis tissue in our pilot group. MPM imaging could be potentially applied in intra-operative diagnosis of testicular tumors especially in testis-sparing surgery. Additional imaging of non-seminomatous germ cell tumors and non-germ cell tumors need to performed to verify the ultimate role of this technology.