Assessing the online objective structured clinical examinations in urology qualifying exam for urology residents in Indonesia during COVID-19 time.

This project aimed to assess the Online National Board of Urology Objective Structured Clinical Examination (OSCE) feasibility in evaluating candidates simultaneously from five urology training centers in Indonesia during the COVID-19 pandemic. Data were collected from two online OSCE simulation trials and the Online National Board of Urology OSCE. A self-administered questionnaire was used to assess examiners and candidates' perception. The average final score of the Online OSCE was compared to previous face-to-face OSCE results. All candidates and examiners (100%) heard and saw clearly the audio-visual in both OSCE simulation trials. None of the candidates had a failing score on the mock exam from all stations. There was a statistically significant difference between the online OSCE and December 2019 face-to-face OSCE. The Online National Board Urology OSCE was feasible and comparable to face-to-face OSCE in evaluating urology candidates. It may be beneficial for the future OSCE method in the medical education system.•Objective Structured Clinical Examination (OSCE) which assesses a broad range of urology candidates' high-level clinical skills, is a more valid and reliable assessment instrument than the traditional oral examination•The Online National Board of Urology OSCE method can help evaluate urology candidates, especially during the unprecedented COVID-19 pandemic.

Comparison of Visual Prostate Symptom Score with the International Prostate Symptom Score and uroflowmetry parameters in assessing men with lower urinary tract symptoms in Dr. Cipto Mangunkusumo National General Hospital, Indonesia.

BACKGROUND: The complexity of International Prostate Symptom Score (IPSS) as an objective questionnaire for lower urinary tract symptoms might be overcome with alternative questionnaire such as the Visual Prostate Symptom Score (VPSS) which uses pictograms instead of questions to illustrate some of the questions addressed in IPSS. METHODS: Male patients older than 45 years with lower urinary tract symptoms were evaluated with Indonesian version of the IPSS and VPSS, for uroflowmetry parameters using a transabdominal ultrasound. Appropriate statistical analysis was used. RESULTS: Of all participants, 24.2% and 11.1% require assistance when answering IPSS and VPSS questionnaires, respectively. The mean age, IPSS total score, VPSS total score, Qmax, voided volume, and postvoid residual volume were 67.4 ± 8.9 years, 13.4 ± 7.8, 10.8 ± 2.7, 13.6 ± 8.6 mL/sec, 248 ± 136 mL, and 54.9 ± 68.3 mL, respectively. Total IPSS, IPSS quality of life (QoL), IPSS question (Q) 2, IPSS Q7, and IPSS Q5 were significantly correlated with total VPSS, VPSS QoL, VPSS Q1, VPSS Q2, and VPSS Q3 [correlation coefficient (r) P value: 0.57, <0.001; 0.76, <0.001; 0.39, <0.001; 0.72, <0.001; 0.50, <0.001, respectively]. VPSS Q3 was significantly correlated with Qmax (r, P value: -0.26, <0.001). There was a significant relationship between the level of education and the ability to complete IPSS questionnaire (P < 0.001). There was no significant relationship between the level of education and the ability to complete VPSS questionnaire (P = 0.649). CONCLUSION: The VPSS was significantly correlated with IPSS and Qmax. The novel questionnaire proved useful as an alternative tool for IPSS for assessing men with lower urinary tract symptoms, especially for those with lower level of education.

A higher PSA-density cut-off level in patients with intermediate PSA values for the early detection of prostate cancer.

The use of PSA-density (PSAD) as an indicator for prostate biopsy at intermediate PSA values has generated controversy. There are investigators who consider that the determination of PSAD is futile, and that it is better to do a prostate biopsy based on PSA values alone, TRUS (Transrectal Ultrasound) findings and/or DRE examinations. Asian countries, especially in the Far East, are considered to have a low incidence of prostate cancer (PCa). However, based on western references, we still measure PSA-density with a cut-off level of 0.15 to promote prostate biopsy in patients with intermediate PSA values (4.1-10.0 ng/ml). Our study aims to evaluate the usefulness of PSAD as an indication for biopsy in patients with intermediate serum PSA values. To evaluate the usefulness of this indicator, we conducted a retrospective study of 132 uncatheterized (to minimize potential bias) BPH and PCa cases that were hospitalized in our department between 1995-1997 (3 years). This group comprised 127 BPH and 5 PCa patients. Mean age was 66.1 +/- 7.69 years; mean PSA was 7.92 +/- 9.289 ng/ml; mean prostate volume was 54.1 +/- 26.72 cc; mean PSAD was 0.15 +/- 0.185. More specifically, there were 49 patients with intermediate PSA values (47 BPH & 2 PCa). The receiver operator characteristic (ROC) curve revealed an optimum cut-off level of 0.19. At this level of PSA density, the measured sensitivity was 100% with a specificity of 79%. We concluded that, in our uncatheterized patients (without retention) series, the PSAD cut-off level for prostate biopsy (0.19) was higher than that in the western world (0.12 or 0.15).

Mechanisms associated with abnormal E-cadherin immunoreactivity in human bladder tumors.

The involvement of E-cadherin in the progression of carcinoma is supported by a large number of studies showing an inverse relationship between E-cadherin immunoreactivity and tumor aggressiveness. However, the mechanisms leading to decreased E-cadherin immunoreactivity are still unclear. Comparison of Northern blotting and immunohistochemistry in a series of 49 frozen bladder tumors revealed that, in 16 of 23 tumors with abnormal staining, clear mRNA down-regulation occurred. In the 7 cases without mRNA down-regulation, no structural anomalies of E-cadherin could be detected by Southern blotting, Western blotting or PCR-SSCP. Western blotting confirmed that, in 6 of these tumors, E-cadherin was down-regulated at the protein level. This down-regulation was accompanied by down-regulation of alpha-catenin and, to a lesser extent, of beta- or gamma-catenin. However, Northern-blot analysis indicated that expression of the 3 catenins is maintained at the mRNA level. Thus our data show that, in bladder tumors, mRNA down-regulation accounts for about two thirds (16/23) of tumors with abnormal staining and that post-transcriptional down-regulation of E-cadherin occurs in 6/23 of these tumors.

Expression of periglandular tenascin-C and basement membrane laminin in normal prostate, benign prostatic hyperplasia and prostate carcinoma.

OBJECTIVE: To evaluate the structural relationship of the distribution between tenascin (tenascin-C, an extra-cellular matrix glycoprotein involved in stromal-epithelial interactions in both normal and pathological conditions) and laminin, an important component of the basement membrane, in normal and neoplastic human prostate, and to establish whether changes in the basement membrane are accompanied by changes in tenascin staining. MATERIALS AND METHODS: Seventy-five snap-frozen prostate samples representing normal glands, nodular benign prostatic hyperplasia and prostate carcinoma were stained for tenascin. From these, 15 samples were selected for dual-immunofluorescence staining and a confocal laser scan microscope was used to simultaneously visualize tenascin and laminin immunoreactivity. RESULTS: Tenascin was expressed in the extracellular matrix, mainly at the periphery of the glands, in tumour foci and blood vessels. In cases with intact basement membranes, e.g. normal glands and hyperplastic lesions, tenascin expression was weak. Low- and moderate-grade tumours were characterized by strong tenascin expression, while laminin expression was weak and/or showed discontinuities, indicating disturbances in basement membrane composition. High-grade tumours had sparse tenascin staining and a marked loss of laminin immunoreactivity. CONCLUSION: These results indicate that periglandular tenascin expression correlates with the integrity of the basement membrane in the human prostate. By influencing stromal-epithelial interactions, tenascin may play a role in maintaining tissue homeostasis in the prostate.

Relation between aberrant alpha-catenin expression and loss of E-cadherin function in prostate cancer.

It is now well documented that E-cadherin expression correlates inversely with tumor grade in various carcinomas including prostate cancer. We also demonstrated a statistically significant correlation between decreased E-cadherin expression and progression-free period in early stage patients treated by radical prostatectomy and decreased survival in patients with advanced stage disease. We now study the relationship between E cadherin and alpha-catenin expression, because in prostate cancer cell lines, mutational inactivation of the alpha-catenin gene can be the cause of the impaired E-cadherin function. Twenty patients treated by radical prostatectomy and 32 advanced stage patients were evaluated immunohistochemically for E-cadherin and alpha-catenin expression. The results were related to tumor grade and disease progression. Four patients in the radical prostatectomy group had aberrant E-cadherin and alpha-catenin expression and showed disease progression. The other 16 patients were free of progression and had normal E-cadherin and alpha-catenin expression. In the advanced stage group, 4 of 13 patients with normal E-cadherin staining showed aberrant alpha-catenin expression and 2 patients (50%) progressed, compared with only 22% progression in patients with both normal E-cadherin and alpha-catenin expression. The other 19 patients with aberrant E-cadherin and alpha-catenin staining had the poorest prognosis. Our results suggest that loss of alpha-catenin expression could be one of the mechanisms responsible for the loss of E-cadherin-mediated cell-cell adhesion in human prostate cancer and might in some cases provide prognostic information.

Changes in keratin expression during the development of benign prostatic hyperplasia.

OBJECTIVE: The relationship between different types of epithelial cells in the prostate and the regulatory mechanism underlying benign prostatic hyperplasia (BPH) are still obscure as is the association between BPH and prostate carcinoma (PCa.) On the basis of keratin immunophenotyping, a subpopulation of cells in normal rat prostate and human PCa have been identified as candidates for the 'amplifying cell' in the stem cell model. In this model the basal cell is described as being associated with the stem cell. From this precursor an intermediate cell type develops which may differentiate into the luminal-type cell. In this study these different cell types are investigated in the development of isolated BPH and BPH associated with PCa, using monoclonal antibodies to intermediate filaments of the keratin class. METHODS: We immunohistochemically stained 64 snap-frozen human prostatic tissues, using monoclonal antibodies against keratin 14 (marker for putative 'stem cell'), keratin 18 (marker for putative 'transit cell'), and MAb RCK103 (marker for putative 'amplifying cell' or intermediate cell). RESULTS: In basal cell hyperplasia, an atypical form of BPH, keratins previously associated with intermediate cells were frequently detected. Cells with this keratin phenotype were detected in the luminal compartment of BPH, and were more prevalent in BPH adjacent to PCa. This keratin expression pattern was similar to that of PCa. CONCLUSION: On the basis of keratin phenotyping we demonstrated that large numbers of cells with the keratin expression pattern of so-called intermediate cells were identified in BPH associated with PCa, while in isolated BPH these cells were infrequently found. This supports the concept that BPH with intermediate phenotype may have premalignant potential. Furthermore this is suggestive of an etiologic relationship between the two diseases.

Expression of markers for transitional cell carcinoma in normal bladder mucosa of patients with bladder cancer.

PURPOSE: Because we have found that random mucosal biopsies have no additional prognostic value to conventional histopathology, we studied biopsies of histologically normal bladder mucosa with several molecular markers believed to be associated with the development of transitional cell carcinoma. MATERIALS AND METHODS: Six groups of patients with an increasing stage of bladder tumor were selected: (1) benign disease (for example, benign prostatic hyperplasia, n = 8); (2-4) low (n = 10), intermediate (n = 9) and high risk (n = 7) superficial tumors; (5) progressive superficial tumors resistant to optimal conservative therapy (n = 6); (6) invasive or disseminated tumors at presentation (n = 5). We studied the expression of cytokeratin (used as an epithelial marker), fibronectin, E-cadherin (HECD-1), I-CAM, human leukocyte antigen (HLA)-I, HLA-II and epidermal growth factor receptor (EGF-R) in cold-cup biopsies of normal mucosa. RESULTS: Fibronectin, HECD-1, I-CAM and HLA-II expression showed no significant changes in the different groups. There was a significant increase in the expression of HLA-I (p = .003) and EGF-R (p = .0001) with a higher stage of the tumor. CONCLUSION: An increasing EGF-R expression in normal looking mucosa of patients with increasing stages of bladder tumors could be a prognostic factor or might indicate that this increase in expression is not tumor specific but is seen in the whole bladder.

Decreased E-cadherin expression is associated with poor prognosis in patients with prostate cancer.

Decreased levels of the cell-cell adhesion molecule E-cadherin are associated with loss of differentiation in a number of human carcinomas. However, the value of E-cadherin as a prognostic marker in these cancers is largely undetermined. A previous study of E-cadherin levels in prostate cancer revealed that almost 50% of tumors examined had reduced or absent levels of this protein (Umbas et al., Cancer Res., 52: 5104-5109, 1992). To determine the potential prognostic significance of this finding, prostate cancer specimens from 89 patients were evaluated immunohistochemically for E-cadherin expression, and the results were related to histopathological grade, tumor stage, presence of metastases, and survival. As previously observed, a significant inverse correlation was found between E-cadherin expression and tumor grade. Importantly, we also found significant correlations between E-cadherin expression and tumor stage and overall survival. Sixty-three percent of the tumors that extended beyond the prostate capsule (T3-4) versus 33% of the tumors confined to the prostate (T1-2) had aberrant expression (chi 2 = 8.1, P < 0.005). Seventy-six percent of the primary tumors from patients that presented with metastases showed aberrant staining compared to 32% from patients without metastases (chi 2 = 14.9; P < 0.001). The life table analysis showed a significantly higher survival rate for patients with normal staining compared to patients with aberrant expression (chi 2 = 20.4, P < 0.001 by log rank test). Moreover, abnormal expression of E-cadherin correlated significantly with progression after radical prostatectomy (P < 0.005). These results suggest that E-cadherin expression can serve as a prognostic indicator for the biological potential of prostate cancer.

Increased expression of high mobility group protein I(Y) in high grade prostatic cancer determined by in situ hybridization.

In a previous study using the Dunning rat prostate cancer model, we found high mobility group protein I-(Y) [HMG-I(Y)] to be overexpressed in metastatic tumor lines when compared to nonmetastatic lines. Hence, overexpression of this 12-kDa non-histone chromosomal protein may be associated with tumor progression. Firstly, by Northern analysis we showed that HMG-I(Y) expression increases in high grade prostate tumors. These studies, however, required fresh material, and clinical follow-up was limited. To overcome this problem paraffin-embedded material must be made amenable for determination of HMG-I(Y) expression in retrospective studies. RNA in situ hybridization enables the evaluation of mRNA levels in such material. We studied tumors from 71 patients with prostate cancer. The microscopic analysis of each sample included: (a) hybridization on sections with sense HMG-I(Y) and (b) 28S rRNA probes (nonspecific signal); (c) hybridization with antisense 28S rRNA (RNA preservation); (d) hybridization with an antisense HMG-I(Y) probe [quantification of HMG-I(Y) mRNA in the expressing areas]. Data were quantified using an image analysis system. High expression of HMG-I(Y) was observed in regions with high Gleason grade (4 and 5); whereas in lesions of Gleason grade 3, both weak and no expression was observed. In areas of grade 1 and 2, as well as in normal glands, low or no expression was found. We conclude that HMG-I(Y) expression assessed by RNA in situ hybridization is related to tumor differentiation in prostate cancer. These findings indicate that HMG-I(Y) expression may be a marker in prostate cancer diagnosis, and the possible clinical implication of expression of this gene in malignancy is discussed in this report.

Decreased E-cadherin immunoreactivity correlates with poor survival in patients with bladder tumors.

E-cadherin, an intercellular adhesion molecule, has been shown to behave like an invasion suppressor gene in vitro. This may explain the inverse relation between expression of E-cadherin and tumor grade that was found in certain cancers. We therefore examined E-cadherin expression in bladder cancer samples from patients with known clinical follow-up. Forty-nine snap-frozen specimens (24 superficial and 25 invasive tumors) and 4 samples of normal urothelium were retrospectively analyzed with anti-E-cadherin monoclonal antibodies. In normal urothelium E-cadherin is expressed homogeneously with a typical membranous staining at cell-cell borders. Decreased expression is found in 5 of 24 superficial tumors and in 19 of 25 invasive cancers. Completely negative tumors are infrequent (4 cases). Most of the time a heterogeneous staining, which may correspond to an unstable E-cadherin expression during tumor development, is seen. Decreased E-cadherin expression correlates with both increased grade and stage (chi 2 = 9.5, P < 0.01, and chi 2 = 14.9, P < 0.005, respectively). More importantly, abnormal E-cadherin expression correlates with shorter survival (log rank test: chi 2 = 16.5, P < 0.001). In keeping with its in vitro invasion suppressor function, decreased E-cadherin expression correlates with the clinical aggressiveness of bladder tumors. This is the first report of E-cadherin as a marker with prognostic value. This parameter must now be tested in a large prospective study to assess its precise clinical relevance.

Expression of the cellular adhesion molecule E-cadherin is reduced or absent in high-grade prostate cancer.

E-cadherin is a Ca(2+)-dependent cell adhesion molecule which plays an important role in normal growth and development via mediation of homotypic, homophilic cell-cell interaction. Recent studies suggest that E-cadherin may be important in neoplastic progression as well, particularly as a suppressor of invasion. We have previously demonstrated that the invasive phenotype of rat prostate cancer cells is associated with the decreased expression of E-cadherin (M. J. G. Bussemakers, R. J. A. Van Moorselaar, L. A. Giroldi, T. Ichikawa, J. T. Isaacs, F. M. J. Debruyne, and J. A. Schalken, Cancer Res., 52:2916-2922, 1992). This is of particular interest, since the locus to which the human E-cadherin gene is mapped is frequently involved in allelic loss in prostate cancer (B. S. Carter, C. M. Ewing, W. S. Ward, B. F. Treiger, T. W. Aalders, J. A. Schalken, J. I. Epstein, and W. B. Isaacs, Proc. Natl. Acad. Sci. USA, 87:8751-8755, 1990; U. S. Bergerheim, K. Kunimi, V. P. Collins, and P. Ekman, Genes, Chromosomes Cancer, 3: 215-220, 1991). Impaired E-cadherin function is likely to be associated with aberrant expression of the protein. We therefore analyzed E-cadherin expression in situ by immunohistochemistry in nonmalignant and malignant specimens of human prostatic tissue. Of 92 tumor samples of either primary or metastatic deposits of prostate cancer, 46 had reduced or absent E-cadherin staining when compared to nomalignant prostate, which uniformly stained strongly positive. There was a statistically significant correlation between the decreased expression of E-cadherin and loss of tumor differentiation. Additionally, certain tumors within a histologically similar group could be distinguished by the presence of mixed populations of E-cadherin-negative and -positive cells. The percentage of tumors with aberrant E-cadherin staining increased when clinically localized tumors were compared to either tumors with extensive local progression or metastatic deposits of prostate cancer, suggesting a correlation between loss of E-cadherin and tumor progression. Taken together, these findings suggest that further exploration of E-cadherin as a candidate invasion suppressor molecule in human prostate cancer is warranted.