Primary osteosarcoma of the uterus: a report of two cases.

Primary extraskeletal osteosarcoma is an uncommon disease and has been reported to affect the uterus only rarely. Less than 20 cases have so far been reported in the English literature. The common clinical presentation is heavy bleeding per vaginam, and in virtually all cases, the diagnosis has been made at an advanced stage of the disease. Various authors have recommended adjuvant chemotherapy, but outcomes have so far been uniformly poor, with survival extended by months rather than years. We present two cases of this rare condition, which were diagnosed four months apart within our histopathology laboratory andconfirmed the very late presentation of the disease in one and the poor survival of both patients. Funding: None declared.

The pathologist in Ghana and potential for research.

One of the neglected areas of clinical medical practice in developing countries is the field of Laboratory Medicine. As a result, the important role of the laboratory physician in diagnosis of disease and subsequent management of patients is not much appreciated. Even more worrying is lack of appreciation of the research potential of laboratory medicine, considering that it provides a repository of confirmatory data on many human disorders; data that have been usefully employed for the study of various diseases in developed parts of the world. It is perhaps, the reason that many diseases peculiar to developing countries still remain untamed. My experience in the practice of anatomical pathology in several countries has taught me that the specialty, as with other specialties of laboratory medicine in Ghana needs more attention, with regards to its development to the level where it can meet its clinical functions satisfactorily. When this is ensured, it would also provide the necessary vital contribution to research that has characterised its practice in more advanced countries. More exposure of the specialty to undergraduate medical students must be encouraged in order to attract trainees into the specialty. Along with this exposure must go an increase in infrastructure and the necessary facilities to permit growth of the specialty. Research potential of the specialty must be harnessed and fully supported financially to help in unravelling peculiar disease problems of our locality. To achieve this, I have re-emphasised the need for a special fund to drive scientific research in Ghana. FUNDING: None.

Ovarian Tumors in Children and Adolescents: A 10-Yr Histopathologic Review in Korle-Bu Teaching Hospital, Ghana.

To determine the histopathologic types, frequency of occurrence, age distribution, presenting signs, and symptoms of ovarian tumors in children and adolescents diagnosed at the Korle-Bu Teaching Hospital all histopathology slides and request cards of ovarian tumors diagnosed in subjects aged, 0 to 19 yr over a 10-yr period (2001-2010) were reviewed. Biographical and clinical data of the patients were collected. The results were entered into Epi-info to determine the frequency of various ovarian tumors in different age groups and their association with presenting signs and symptoms. A total of 67 (9.5%) ovarian tumors were diagnosed in patients aged 0 to 19 yr of a total of 706 diagnosed in all age groups during the period. The majority [44 (65.7%)] were germ cell tumors, the commonest being mature cystic teratoma. Burkitt lymphoma was the single most common malignant tumor, comprising 6(9%) of all the tumors, although as a group malignant germ cell tumors were still the most common malignant ovarian tumors in children and adolescents. Although germ cell tumors were the most common tumors in this age group (both benign and malignant), Burkitt lymphoma, a peculiar malignant tumor in this subregion, was the single most common malignant tumor of the ovary.

Molecular basis for the effects of zinc deficiency on spermatogenesis: An experimental study in the Sprague-dawley rat model.

INTRODUCTION: The objective of this study is to investigate the molecular mechanisms underlying the effects of zinc deficiency on spermatogenesis in the Sprague-Dawley (SD) rat. MATERIALS AND METHODS: Three groups of eight adult male SD rats were maintained for 4 weeks on a normal diet as control, zinc deficient diet and zinc deficient diet with zinc supplementation of 28 mg zinc/kg body weight respectively. Using standard techniques, the following parameters were compared between the three groups of experimental animals at the end of 4 weeks: (a) Serum zinc, magnesium (Mg), copper (Cu), selenium (Se) and cadmium (Cd), (b) serum sex hormones, malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPX), (c) interleukin-4 (IL-4), tumor necrosis factor-alpha (TNF-α), Bcl-2, Bax and caspase-3 expression in the testes, (d) assessment of apoptosis of testicular cells using electron microscopy and (e) testicular volume and histology using the orchidometer and Johnsen score, respectively. RESULTS: The zinc deficient group showed a reduction of testicular volume, serum concentrations of Zn, Cu, Se, Mg, SOD, GPX, IL-4, Bcl-2 and testosterone (P < 0.05), as well as increased levels of serum Cd, MDA and tissue TNF-α, Bax, caspase-3 and apoptosis of the germ cells (P < 0.05) compared with control and zinc supplementation groups. CONCLUSION: Zinc deficiency is associated with impaired spermatogenesis because of reduced testosterone production, increased oxidative stress and apoptosis. These findings suggest that zinc has a role in male reproduction.

Ovarian Cancer in Ghana, a 10 Year Histopathological Review of Cases at Korle Bu Teaching Hospital.

To determine the histopathological types, age distribution, presenting signs and symptoms of ovarian cancers diagnosed at the Korle-Bu Teaching Hospital, Ghana. All histopathology slides and request cards of ovarian cancers diagnosed over a ten-year period (2001 to 2010) were reviewed and the cancers classified according to the World Health Organization 1999 classification. Biographical and clinical data of the patients were collected and results entered into Epi-info to determine the frequency, age distribution and clinical presentation of the various types of ovarian cancer. There were 192 (27.2%) ovarian cancers out of 706 ovarian tumours. Epithelial cancers were the most common: 100 (52.1%), followed by sex cord stromal cancers 66 (34.4%). Majority of epithelial cancers were serous adenocarcinomas (71/100) while most sex cord stromal cancers were adult granulosa cell tumours 46 (69.7%). The mean age of patients with adenocarcinoma was 49 years while that of the 46 adult granulosa cell tumours was 46.5 years. Patients present with varying combinations of symptoms and signs and ovarian cancers present at an earlier age compared to other populations, with the age of presentation being slightly lower for sex cord stromal cancers compared to adenocarcinomas. There are no specific symptoms or signs associated with ovarian cancer at presentation, to assist with diagnosis.

Combined ciprofloxacin and amikacin prophylaxis in the prevention of septicemia after transrectal ultrasound guided biopsy of the prostate.

PURPOSE: A steady increase in the incidence of septicemia after prostate biopsy in our unit between 2001 and 2005 prompted us to review our prophylactic antibiotic regimen. We compared the incidence of septicemia in patients undergoing prostate biopsy between 2001 and 2005 when only oral ciprofloxacin was used prophylactically (group 1) to the incidence among patients undergoing biopsy between 2006 and 2010 when a single dose of intravenous amikacin was added to ciprofloxacin (group 2). MATERIALS AND METHODS: In group 1 the 300 patients were given 500 mg oral ciprofloxacin twice daily 1 day before and for 2 days after the biopsy while in group 2 the 897 patients, in addition to the ciprofloxacin previously mentioned, received 500 mg intravenous amikacin 30 minutes before the biopsy. Patients admitted to the hospital with septicemia after prostate biopsy had urine and blood culture and sensitivity tests. The number of patients in whom septicemia developed in each group after prostate biopsy and the microorganisms isolated from the urine and blood of such patients were compared using the chi-square test. RESULTS: Septicemia was seen in 24 of 300 (8%) and 15 of 897 (1.7%) patients in groups 1 and 2, respectively (p <0.001). In group 1 the rate of septicemia after prostate biopsy was 2.1% and 13% in 2001 and 2005, respectively (p <0.001). In group 2 the rate of septicemia was 1.5% in 2006 and 1.6% in 2010 (p <0.25). Escherichia coli resistant to quinolones was responsible for 33 of 39 (84.6%) septicemic cases. CONCLUSIONS: The addition of amikacin to ciprofloxacin prophylaxis significantly reduces the incidence of septicemia after prostate biopsy.

The role of combined measurement of tissue mRNA levels of AMACR and survivin in the diagnosis and risk stratification of patients with suspected prostate cancer.

AIM: To determine whether the measurement of tissue mRNA levels of AMACR and survivin has a role in distinguishing prostate cancer (PCa) from benign lesions and high risk from low-risk PCa in men with suspected PCa. METHODS: TRUS prostate biopsies from 170 patients with suspected PCa were used to measure the mRNA levels of AMACR and survivin using semi-quantitative RT-PCR technique. The diagnosis, staging and risk stratification of PCa was based on established clinical criteria. The ability of tissue mRNA levels to distinguish benign from malignant prostate and high- and low-risk PCa was assessed. The diagnostic value for the two genes was evaluated by calculating their individual and combined sensitivity and specificity, which were compared with that of PSA. RESULTS: Histological examination showed 90/170 (53%) of patients had benign prostate pathology, while 80/170 (47%) had PCa. Tissue mRNA levels of both AMACR and survivin were able to distinguish benign from PCa biopsies (p<0.0001) and also high-risk from low-risk PCa cases (p<0.02, p<0.05, respectively). Compared with serum PSA levels, the combined use of tissue mRNA levels of AMACR and survivin yielded a higher detection specificity (84 vs. 22%). CONCLUSION: Based on AMACR and survivin combined sensitivity and specificity, these mRNA markers can be used as an adjunct to distinguish patients with and without PCa and in men with PCa may help to identify those with low- or high-risk PCa.

The effect of prostate tissue inflammation in benign prostatic hyperplasia on enhancer of zeste homolog 2 ribonucleic acid expression.

BACKGROUND AND OBJECTIVES: Enhancer of zeste homolog 2 (EZH2) has been recently found to regulate several genes involved in immunoresponse and autocrine inflammation network. The aim of the study was to quantitate EZH2 messenger ribonucleic acid (mRNA) expression, evaluate its relation to conditions of prostatitis associated with benign prostatic hyperplasia (BPH), and correlate it with the levels of the inflammatory marker interlukin 6 (IL-6). DESIGN AND SETTING: Cross-sectional study in Middle Eastern men with BPH and prostatitis or BPH only. PATIENTS AND METHODS: Transrectal ultrasound-guided prostate biopsies were collected from 106 patients suspected of having prostate cancer; however, the histology revealed BPH. Upon further pathological examination, 56 of these cases were identified as BPH with prostatitis and classified as: acute prostatitis (n=13); active chronic prostatitis (n=32); and, chronic inactive prostatitis (n=12). Serum IL-6 levels and EZH2 mRNA expression were measured and compared between patient groups. RESULTS: EZH2 mRNA was overexpressed in BPH with prostatitis patients compared to BPH only patients (P<.0001). BPH with active chronic prostatitis had higher EZH2 expression than BPH with acute or chronic inactive prostatitis compared to BPH only (P=.05 and .73, respectively). EZH2 mRNA expression showed a negative correlation with IL-6 concentrations in BPH with prostatitis patients (rs=-0.31, P=.02). EZH2 overexpression was associated with an increased risk of having BPH with prostatitis (crude odds ratio 0.20, 95% CI 0.06-0.65, P=.0076). CONCLUSIONS: EZH2 mRNA expression correlates positively with prostatitis conditions associated with BPH and negatively with serum IL-6 levels. This supports the possible involvement of EZH2 mRNA overexpression in the development of prostate inflammation, and its new regulatory role in suppressing the expression of some inflammatory network genes.

Urinary survivin mRNA expression and urinary nuclear matrix protein 22 BladderChek® and urine cytology in the detection of transitional cell carcinoma of the bladder.

OBJECTIVE: To compare the diagnostic performance of urine cytology (UC), survivin mRNA expression, and the NMP22 BladderChek® (NMP22BC) test for the detection, grading and staging of transitional cell carcinoma (TCC) of the bladder. MATERIALS AND METHODS: Voided urine samples collected from 25 healthy controls and 80 patients diagnosed with TCC of the bladder were subjected to UC, the NMP22BC test and reverse-transcription real-time PCR for survivin mRNA expression. RESULTS: Survivin mRNA expression showed the highest sensitivity (87.5%) followed by the NMP22BC test (61.3%) while UC exhibited the lowest sensitivity (40%). All three urine markers had a similar specificity of 96% (95% CI 80.5-99.3%). Survivin mRNA expression was the only urine marker that showed a significant difference in relation to tumour histological grade (χ(2) 8.5, p = 0.015). None of the three urine markers was significantly related to tumour pathological stages. CONCLUSION: The diagnostic sensitivity of urinary survivin mRNA expression was superior to that of UC and the NMP22BC test and correlates with tumour pathological grade but not stage.

Survivin downregulation is associated with vasectomy-induced spermatogenic damage and apoptosis.

OBJECTIVE: To evaluate the expression of the apoptotic genes survivin, Bax and Bcl-2 in vasectomized rabbits and to determine their relation with vasectomy-induced spermatogenic impairment and germ cell apoptosis. MATERIALS AND METHODS: Twelve adult rabbits (6-12 months old) were divided into three groups: sham control, unilateral vasectomy or bilateral vasectomy. Six months after vasectomy, testicular tissue was analyzed for germ cell apoptosis and DNA fragmentation by the TUNEL assay and gel electrophoresis, respectively. Spermatogenesis was assessed using the Johnsen score. The relative gene expression of survivin, Bax and Bcl-2 was measured using reverse transcription followed by real-time PCR. RESULTS: Compared to sham animals, a significant decrease in testicular survivin mRNA levels was measured in the two vasectomy animal groups (p < 0.05). This was accompanied by a significant increase in the Bax:Bcl-2 ratio in the vasectomized animals (p < 0.05). In addition, these data showed positive correlation with enhanced apoptotic index, damage to spermatogenesis and DNA fragmentation after vasectomy. CONCLUSION: These findings demonstrate that vasectomy-induced damage to spermatogenesis due to testicular apoptosis may be associated with survivin downregulation and Bax overexpression.

Comparison of the sensitivity and specificity of urine cytology, urinary nuclear matrix protein-22 and multitarget fluorescence in situ hybridization assay in the detection of bladder cancer.

OBJECTIVE: This study aimed to compare the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of urine cytology, BladderChek® nuclear matrix protein-22 (NMP22) and UroVysion™ fluorescence in situ hybridization (FISH) tests in patients with newly diagnosed bladder cancer, those with recurrent bladder cancer, and those with bladder cancer but in remission during surveillance. MATERIAL AND METHODS: Voided urine samples obtained from 178 patients with suspected or known bladder cancer about to undergo diagnostic or surveillance cystoscopy and 25 control subjects without the disease were divided into four and used for urine culture and cytology, NMP22 BladderChek and UroVysion FISH tests. The sensitivity, specificity, PPV and NPV for each test were calculated. Comparison was made between the ability of each test to detect bladder cancer in the three category of patients listed. RESULTS: Of the 178 patients with bladder cancer, 43 were newly diagnosed, 58 had recurrent disease and 77 were in remission. The sensitivity of each test in newly diagnosed patients was: urine cytology 28%, NMP22 88% and FISH 80%; and in patients with recurrent disease: urine cytology 33%, NMP22 57% and FISH 85%. The mean specificity for urine cytology, NMP22 and FISH was 95%, 67% and 48%, respectively. CONCLUSION: Of the tests used in the study for detection of bladder cancer, NMP22 appeared to be most cost-effective and rapid, with relatively high sensitivity and specificity in all categories of patients. The NMP22 test may be considered a new gold standard for the assessment of patients with known or suspected bladder cancer.

Long term testicular ischemia-reperfusion injury-induced apoptosis: involvement of survivin down-regulation.

Testicular torsion is associated with damage to the testicular tissue as a result of ischemia-reperfusion injury (IRI) and induction of apoptosis leading to progressive damage to spermatogenesis. Survivin is suggested to be an important regulator in the control of the mitochondrial apoptotic pathway, although its role in torsion-induced IRI is unknown. Therefore, we sought to evaluate testicular survivin expression after long term IRI induced by testicular torsion. Survivin expression was measured by real-time PCR in 6-12 month old New Zealand white rabbits divided into three groups (4 animals/group): group (A) sham control, group (B) ischemia alone for 60 min and group (C) ischemia for 60 min followed by reperfusion for 6 months. Germ cell apoptosis was evaluated by TUNEL assay, Bax/Bcl-2 ratio and DNA fragmentation. The Johnsen score was used to assess testicular morphological damage, while lipid peroxidation was used as an indicator for oxidative stress. Survivin expression was detected in all testicular tissue samples. The rate of survivin expression after IRI was significantly higher (p<0.05) compared with ischemic only and sham control testes. Its expression in IRI samples was inversely correlated with the significant increase (p<0.05) in apoptosis, oxidative levels and spermatogenic damage. In conclusion, down-regulation of testicular survivin expression after long term IRI to the testis and its association with apoptosis induction suggests its involvement in the regulation of this apoptotic pathway. These findings also identify survivin as a potential new target for the prevention of germ cell death during testicular torsion.

Parasites of urological importance.

With the world increasingly becoming a global village, transnational and transcontinental migration has become the order of the day. It is expected that migrants will take with them some diseases (including parasites) which are normally endemic in their countries of origin, to their host countries. Similarly, environmental changes that result from development of water resources, global warming, growth and migration of population can facilitate the spread of parasites. In this review we describe the epidemiology, presentation, diagnosis and treatment options of parasites that urologists may encounter. Notably among these parasites are Schistosoma haematobium, Echinococcus granulosus, Wuchereria bancrofti and Onchocerca volvulus.

The importance of determining the aggressiveness of prostate cancer using serum and tissue molecular markers.

Incidental prostate cancer (PCa) has been demonstrated at autopsy in about 80% of men aged 80 years and above and also in 10%-15% of younger men aged 30-50 years in the United States. These data imply a wide variation in aggressiveness of prostate cancer, from indolent tumors to aggressive cancers that kill the patients. The use of prostate specific antigen (PSA) in screening for PCa may detect even indolent disease for which radical prostatectomy may not be necessary. Currently available criteria such as histological grade, PSA level, stage of the disease do not always predict outcome. Furthermore, only about 80% of men with metastatic PCa will respond to first line hormone manipulation and once the patient develops hormone resistant prostate cancer (HRPCa), survival remains poor. Recent genomic and proteomic studies have provided many novel molecular markers that may help to redefine prognostic parameters. This paper is a review of studies using these novel markers in order to determine whether prostate cancer patients with the following characteristics have more aggressive cancer than those without: a) high serum levels of cathepsin B, survivin, Her - 2 / neu, IGFBP-2; b) low serum stefin A, IGFBP-3, c) positive immuno-staining of primary tumors for Her-2/neu, survivin and cathepsin B / stefin A ratio > 1 and d) gene expression of AMACR, HER-2/neu, high Bcl-2: Bax ratio and EZH2 in cancer cells. These markers have been chosen for review because they are among the most promising markers emerging currently.

Experimental colitis is associated with ultrastructural changes in inflamed and uninflamed regions of the gastrointestinal tract.

OBJECTIVES: The objective of this study was to examine the ultrastructural changes in cell organelles such as mitochondria, endoplasmic reticulum (ER) and Golgi apparatus in inflamed colon and uninflamed ileum in colitic rats. MATERIALS AND METHODS: Colitis was induced in rats by intracolonic administration of trinitrobenzenesulfonic acid (TNBS). The animals were sacrificed on day 5 after TNBS administration and colonic and ileal samples were used for estimation of myeloperoxidase (MPO) activity, malondialdehyde (MDA) concentration, histologic examination and transmission electron microscopy. RESULTS: TNBS caused a significant reduction in body weight and an increase in MPO activity in colonic, but not in the ileal samples in animals with colitis. MDA levels were increased both in inflamed colon and the uninflamed ileal segments in colitis. Electron microscopy revealed swelling of mitochondria with broken cristae and disruption of the inner membrane. Colitis also caused fragmentation of the ER with loss of ribosomes and swelling of the Golgi apparatus with distended vesicles in both smooth muscle and epithelial cells in the ileal and colonic segments. These changes were absent in the control rats without colitis. CONCLUSIONS: These findings demonstrate ultrastructural deformities in both the mucosa and smooth muscle in inflamed and uninflamed regions of the gastrointestinal tract in experimental colitis. The structural changes in mitochondria are responsible for reduced ATP, while abnormalities in the ER and the Golgi apparatus may explain a generalized effect on protein synthesis, trafficking and targeting mechanisms, and may account for physiological changes seen in experimental colitis.

Gerodermia osteodysplastica/wrinkly skin syndrome: report of three patients and brief review of the literature.

Gerodermia osteodysplastica and wrinkly skin syndrome are rare autosomal recessive disorders. Due to the many phenotypic similarities in these two conditions, it has been proposed that they represent the same disorder. Both conditions are well delineated in the genetic literature, but despite skin involvement being a striking feature, they are rarely reported in dermatology journals. In this report, we describe three Arab children from two consanguineous families who exhibit overlapping features of gerodermia osteodysplastica and wrinkly skin syndrome. All the patients had dysmorphic facial features, wrinkled skin more marked on the hands and feet, hyperextensible joints, intrauterine growth retardation, developmental delay, congenital dislocation of hips, and osteoporosis. Our observations also support the contention that gerodermia osteodysplastica and wrinkly skin syndrome have the same clinical spectrum; however, this needs to be confirmed at the molecular level.

Relative contribution of digital rectal examination and transrectal ultrasonography in interpreting serum prostate-specific antigen values for screening prostate cancer in Arab men.

BACKGROUND: This study was conducted to determine the utility of digital rectal examination (DRE), transrectal ultrasonography (TRUS) and serum prostate-specific antigen (PSA) in the diagnosis of prostate cancer in men in Arabia, an are of the world with a relatively low incidence of this disease. PATIENTS AND METHODS: 329 patients suspected of having prostate cancer on account of raised serum PSA level (>4 ng/ml), DRE or TRUS findings, underwent TRUS-guided prostate biopsy. Raised PSA individually as well as combined, or a lesion suspicious of carcinoma on DRE or TRUS was recorded as PSA(+), DRE(+) or TRUS(+), respectively. The contribution of DRE, TRUS and serum PSA to the diagnosis of prostate cancer was analysed. RESULTS: Of the 329 patients who had prostate biopsies 109 cases (33.1%) had PCa. Of these 109 patients 56 (51%) had DRE(+), 77 (42%) had TRUS(+) and 49 (66%) had both DRE(+) and TRUS(+). Statistical analysis revealed that DRE(+) tripled the probability for cancer. PSA over a range of 10-50 ng/mL demonstrated an increasing cancer probability ranging from 2 to 3 fold. TRUS(+) was only significantly associated with cancer risk if PSA was elevated. The presence of all three factors increased the cancer probability by 6 to 7 fold. CONCLUSION: TRUS findings are dependent on PSA for interpretation while DRE(+) with elevated PSA makes PCa more likely.

Patients' tolerance and early complications of transrectal sonographically guided prostate biopsy: prospective study of 300 patients.

PURPOSE: To determine the degree of pain and discomfort associated with transrectal sonography (TRS)-guided biopsy of the prostate and to analyze the complications associated with this procedure. METHODS: Three hundred men referred as part of an investigation to exclude prostate cancer were studied. The reasons for referral were suspected prostate cancer due to increased serum prostate-specific antigen level (>4 ng/ml), the finding of a palpable nodule or greater firmness of one prostatic lobe than the other on digital rectal examination, or the finding of a suspicious area of neoplasm of the prostate on TRS biopsy. All TRS-guided biopsies were performed as outpatient procedures without anesthesia. Ciprofloxacin prophylaxis was used in all patients before biopsy. Tolerance of the procedure was recorded immediately after the examination and graded on a scale of 0-4 as follows: 0, no pain; 1, very mild pain; 2, moderate pain; 3, severe pain; 4, intolerable pain. Complications recorded in the first week after the procedure were analyzed. They included mild pain, self-limiting hematuria, hematospermia, rectal bleeding, severe hematuria, septicemia, severe hemorrhage of the anus, and vasovagal attack. RESULTS: Out of 300 TRS-guided biopsies, 10 early complications were recorded. The most frequent was septicemia, which was seen in 5 cases (1.7%). Hematuria occurred in 29 patients, 3 of which were severe. Rectal bleeding and vasovagal attack occurred in 1 patient each. All patients made a full recovery with appropriate conservative management. Ten cases (3.33%) of severe pain (grade 3) and intolerable pain (grade 4) were observed. Three out of these 10 patients completed the procedure. The procedure was terminated in 1 patient, and 6 patients required local anesthetic due to perianal disease. CONCLUSIONS: TRS-guided prostate biopsy can be performed without local anesthesia in 90% of patients. Prophylactic antibiotics are mandatory to minimize approximately infectious complications.