[Testicular toxoplasmosis: a rare case of a testicular mass]. / Toxoplasmosis testicular: un caso raro de masa testicular.

Toxoplasma gondii is an intracellular protozoan infecting birds and mammals. Acute infection is asymptomatic in immune competent people. For immune deficient patients (acquired immune deficiency syndrome, lymphoma patients or those under steroids to prevent organ transplantation rejection) infection may be lethal. We describe an uncommon case of testicular toxoplasmosis in patient under steroids after organ transplantation with no positive serum test for HIV and/or systemic toxoplasmosis.

Toxoplasmosis testicular: un caso raro de masa testicular / Testicular toxoplasmosis: a rare case of mass testicular

El Toxoplasma gondii es un protozoario intracelular que infecta aves y mamíferos. La infección aguda es asintomática en pacientes inmunocompetentes. En pacientes con deficiencia inmunológica (síndrome de la inmunodeficiencia adquirida, linfomas o pacientes sometidos a terapia con corticoides para prevención derechazo de transplante de órganos) la infección puede ser fatal. Nosotros describimos un caso poco común de toxoplasmosis testicular en paciente sometido a transplante renal hace 6 años con serología negativa para el virus VIH y sin toxoplasmosis sistémica (AU)

Toxoplasma gondii is an intracellular protozoan infecting birds and mammals. Acute infection is asymptomatic in immune competent people. For immune deficient patients (acquired immune deficiency syndrome, lymphoma patients or those under steroids to prevent organ transplantation rejection) infection may be lethal. We describe an uncommon case of testicular toxoplasmosis in patient under steroids after organ transplantation with no positive serum test for HIV and/or systemic toxoplasmosis (AU)

Natural rubber latex sensitisation and allergy in patients with spina bifida, urogenital disorders and oesophageal atresia compared with a normal paediatric population.

BACKGROUND: Natural rubber latex (NRL) contains proteins which, after repeated contact with latex products and an allergic predisposition (atopy), can lead to sensitisation (specific IgE against NRL proteins) or allergy (type 1 allergy with symptoms from urticaria to allergic shock). Spina bifida patients are known to be a high risk group for latex allergy and sensitisation due to numerous operations beginning soon after birth. In the study presented here we compared spina bifida patients with patients who also underwent repeated operations beginning soon after birth (urological malformations) or underwent surgery once in the neonatal period but had numerous anaesthesias because of repeated treatment with a bougie (oesophageal atresia). In this setting the influence of surgery and anaesthesia on NRL-sensitisation was investigated. MATERIALS AND METHODS: We investigated the prevalence of NRL-specific IgE (> 0.35 kU/l, ImmunoCAP system, Pharmacia) in a normal paediatric population (neither atopic nor having undergone surgery) (group I), spina bifida patients (group II), children with urogenital malformations (group III) and children with oesophago-tracheal malformations (group IV). RESULTS: The highest rate of NRL-sensitised patients was found in the spina bifida group (II) (48 %), followed by groups III and IV with 17 % each, compared to 4 % for the control group. NRL-allergic reactions were noted only in the patients with spina bifida and the urological malformation group (18 % in group II, 8 % in Group III). Apart from atopy the number of operations could be identified as a risk factor for the development of NRL-sensitisation and allergy (group II, III). The prevalence of latex allergy was lower after repeated anaesthesia (group IV) than after repeated surgery. CONCLUSIONS: In addition to the known high risk group of spina bifida patients, other patients with congenital malformations and early surgery also have a significant risk for latex sensitisation. When treating patients with malformations requiring repeated surgery, prophylactic measures similar to those for spina bifida patients should be considered.

Use of bisphosphonates can dramatically improve pain in advanced hormone-refractory prostate cancer patients.

INTRODUCTION: Approximately 85% of patients who die from prostate cancer present the spread of bone metastases. Even though the radiological appearance of such metastases is osteoblastic, it is now known that these lesions coexist in their microenvironment with blastic and lytic lesions. The process always begins with bone lysis by osteoclast proliferation, paralleling nearby bone deposition. The treatment options are palliative and have poor clinical response with short-lived improvement. We have studied the clinical effect of bisphosphonates (clodronate) in the treatment of skeletal complications from prostate cancer. MATERIALS AND METHODS: In an open prospective study, 58 patients with hormone-refractory prostate cancer with bone metastases were assessed from November 2000 to September 2003. The mean age was 70.3 y (range: 51-87 y). Bone scintigraphy, plain X-ray, assaying of prostate-specific antigen (PSA) and biochemical tests were requested before and following treatment. Patients were previously and subsequently assessed using the visual pain scale (0-10) and Karnofsky's index after the first and second intravenous (i.v.) infusions (administration of i.v. clodronate every 28 days) and every 4-6 months thereafter. Student's t-test was used for statistical analysis. RESULTS: A total of 53 patients (91.4%) showed improvement after the first and/or second cycle, which persisted for at least 4 months (average 6.3 months). The averages on the visual pain scale improved from 7.4 (range: 2-8) to 2.4 (0-7) and on Karnofsky's index from 43 (32-58) to 73 (50-82). The radiological appearance of the metastases improved in 27 patients (46.5%) and there were few relapses (six patients; 10.3%). CONCLUSIONS: Clodronate was effective in the treatment of skeletal complications from prostate cancer. There was an objective response in 91.4% of treated patients, with a marked improvement in the subjective visual pain scale evaluation as well as on Karnofsky's index, with low side effects.

Capecitabine in hormone-resistant metastatic prostatic carcinoma - a phase II trial.

The objective of the trial is to evaluate the efficacy of capecitabine in patients with metastatic hormone-resistant prostate carcinoma (HRPC), in terms of prostate-specific antigen (PSA) response and clinical benefit (decrease of pain or analgesic score) and its safety profile. In all, 25 patients with HRPC were enrolled on a phase II trial of capecitabine (Xeloda) at a dose of 1250 mg m(-2) orally twice daily on days 1-14 every 21 days. The inclusion criteria were PSA serum levels >3 x upper limit of normal, a WHO performance status 0-2, age <85 years and adequate bone marrow, liver and renal function. In patients with grade 2 or higher haematological toxicity on day 1 of the treatment cycle, therapy was first delayed, and then continued at a lower dose. Trial end points were PSA response and clinical benefit defined by quality of life (QL) data and analgesic consumption. The median age of patients was 70 years (range 54-85 years). A median of three cycles of capecitabine was administered (range 1-8). PSA response was observed in three patients (12%, 95% CI 3-31%), with times to tumour progression of 18, 21 and 35 weeks, respectively. In these patients, the response durations were 12, 17 and 32 weeks, respectively. Minor PSA regression was also seen in two further patients. The median time to tumour progression of all patients was 12 weeks (95% CI 9-15 weeks). Haematological toxicity was minor, with leukopenia grade 3 observed in one patient. There were three deaths during trial treatment, respectively, due to sepsis following mucositis and leukopenia, presumed sepsis with mucositis induced by chemotherapy and concomitant radiotherapy and cerebral dysfunction progressing to coma. Hand-foot syndrome grades 2 and 3 were observed in four patients each. Clinical benefit was observed in five patients (20%, CI 7-41%). Based on toxicity data, we recommend a lower starting dose of 1000 mg x m(-2) orally twice daily. While capecitabine has some activity in HRPC, as suggested by observed PSA responses, we conclude that it is not worthwhile to investigate capecitabine monotherapy in a phase III trial. Combinations of capecitabine with other agents, such as vinorelbine or docetaxel, may prove to be more effective.

Vinorelbine in androgen-independent metastatic prostatic carcinoma--a phase II study.

The purpose of this study was to evaluate the efficacy of vinorelbine treatment in terms of prostate-specific antigen (PSA) response and clinical benefit (decrease of pain or analgesic score for the subgroup of patients with pain), as well as its toxicity in patients with progressive metastatic androgen-independent prostatic carcinoma. 44 patients with prostatic carcinoma progressing after orchiectomy or during treatment with hormonal agents were treated with vinorelbine at a dose of 30 mg/m(2) intravenously (i.v.) on days 1 and 8 of a 21-day cycle. Inclusion criteria were metastatic progressive prostatic carcinoma with prostate-specific antigen (PSA) serum levels >/=3 x upper limit of normal, World Health Organization (WHO) performance status /=2 was observed on the day of scheduled vinorelbine administration. 9 patients received less than three cycles, 6 due to rapid tumour progression. Treatment at day 1 had to be delayed in 13.7% of 183 cycles. Treatment at day 8 had to be omitted in 19.7% of all cycles. Grade >/=3 granulocytopenia occurred in 18% of patients. 4 patients had severe constipation. In 7 patients (15.9%, Confidence Interval (CI) 6.6-30.1%), a PSA response (>/=50% reduction of PSA levels) was observed. Among 8 patients with measurable disease, 3 had partial remission and 1 no change. Median time to PSA progression in 43 assessable patients was 11.9 weeks (range 3-52 weeks). Median duration of PSA response was 14 weeks (9-30 weeks). Clinical benefit was seen in 7 of 31 cases (23%) with baseline pain, there was no association with PSA response. Vinorelbine is a fairly well tolerated drug with a moderate single agent activity in patients with androgen-refractory prostate cancer.

Reduction of latex sensitisation in spina bifida patients by a primary prophylaxis programme (five years experience).

Spina bifida patients represent a group with the highest risk for latex sensitisation and allergy with life-threatening symptoms mostly during surgery. At the end of 1995 we initiated a primary latex prophylaxis around and during surgery and anaesthesia of all spina bifida patients. The aim of our study was to investigate the prevalence of latex sensitisation in the spina bifida patients born during the five years after establishing latex prophylaxis in the Cologne Children's Hospital in December 1995. We investigated 34 serum samples of 27 spina bifida patients (mean age 2.4 years) for specific IgE antibodies against latex allergens (CAP system) and compared these patients born after 1995 with 38 spina bifida patients up to 5 years of age (mean 3.1 years) born before. In the prophylaxis group two of 27 patients (7 %), one of them with two operations outside the Children's Hospital, had low specific IgE against latex ( 100 kU/l (mean 22.6 kU/l, min 0.4 kU/l). Sera of 22 patients remained negative for latex IgE (min. 1, max. 19, mean 4.3 operations). By primary latex prophylaxis during surgery, anaesthesia and in paediatric wards the prevalence of latex sensitisation can be significantly reduced even in the high risk group of spina bifida patients. Problems can arise by the need for surgery in hospitals not experienced in the treatment of spina bifida patients, where latex prophylaxis is neglected.

Comparison of positivity frequency of bcl-2 expression in prostate adenocarcinoma with low and high Gleason score.

CONTEXT: Multiple genetic and epigenetic factors have been implicated in the oncogenesis and progression of prostate cancer. The major difficulty is in that the clinical management stems from the reality that reliable and accurate prognostic biomarkers are not available and that effective treatment regimens forming hormone-resistant prostate cancers are yet to be developed. Among the most important regulators of apoptosis and programmed cell death is the bcl-2 gene and its related proteins. Elevated levels of bcl-2 protein may contribute to the progression of prostate cancers to a metastatic and hormone-insensitive state characterized by poor responses to chemotherapy. OBJECTIVE: To characterize the expression of bcl-2 proteins as a prognostic factor in humans. DESIGN: A retrospective approach. SETTING: Urology section, Federal University of São Paulo. DIAGNOSTIC TEST USED: Immunohistochemical analysis using bcl-2 protein antibody and normal staining by hematoxylin-eosin. MAIN MEASUREMENTS: Prognostic relations and protein expression were evaluated considering the total sample (28) divided into two groups, high (8 to 10) and low (2 to 4), separated according to the histological differentiation grade (Gleason score) with 10 and 18 samples, respectively. RESULTS: The differentiation of grade into two groups separated according to the Gleason score in low and high types presented different bcl-2 expression (P < 0.001). CONCLUSION: The higher frequency of bcl-2 immunostaining in tumor samples was observed in association with more advanced Gleason scores and suggests that an increase in the ratio of this anti-apoptotic protein often occurs during progression of prostate cancers.

Microarrays of bladder cancer tissue are highly representative of proliferation index and histological grade.

The number of genes suggested to play a role in cancer biology is rapidly increasing. To be able to test a large number of molecular parameters in sufficiently large series of primary tumours, a tissue microarray (TMA) approach has been developed where samples from up to 1000 tumours can be simultaneously analysed on one glass slide. Because of the small size of the individual arrayed tissue samples (diameter 0.6 mm), the question arises of whether these specimens are representative of their donor tumours. To investigate how representative are the results obtained on TMAs, a set of 2317 bladder tumours that had been previously analysed for histological grade and Ki67 labelling index (LI) was used to construct four replica TMAs from different areas of each tumour. Clinical follow-up information was available from 1092 patients. The histological grade and the Ki67 LI were determined for every arrayed tumour sample (4x2317 analyses each). Despite discrepancies in individual cases, the grade and Ki67 information obtained on minute arrayed samples were highly similar to the data obtained on large sections (p<0.0001). Most importantly, every individual association between grade or Ki67 LI and tumour stage or prognosis (recurrence, progression, tumour-specific survival) that was observed in large section analysis could be fully reproduced on all four replica TMAs. These results show that intra-tumour heterogeneity does not significantly affect the ability to detect clinico-pathological correlations on TMAs, probably because of the large number of tumours that can be included in TMA studies. TMAs are a powerful tool for rapid identification of the biological or clinical significance of molecular alterations in bladder cancer and other tumour types.

High-throughput tissue microarray analysis of 3p25 (RAF1) and 8p12 (FGFR1) copy number alterations in urinary bladder cancer.

Studies by comparative genomic hybridization revealed that the chromosomal regions 3p25 and 8p11-p12 are recurrently amplified in bladder cancer. To investigate the prevalence of DNA copy number alterations in these chromosomal regions and study their clinical significance, we used probes for the RAF1 (3p25) and FGFR1 (8p12) genes for fluorescence in situ hybridization. A tissue microarray containing 2317 tumors was analyzed. The analysis revealed RAF1 amplification in 4.0% and FGFR1 amplification in 3.4% of interpretable tumors. In addition, deletions were found at the 3p25 locus in 2.2% and at the 8p11-12 locus in 9.9% of interpretable tumors. Both amplifications and deletions of RAF1 and FGFR1 were significantly associated with high tumor grade (P < 0.0001), advanced stage (P < 0.0001), and poor survival (P < 0.05) if tumors of all of the stages where analyzed together. RAF1 amplifications were associated with subsequent tumor progression in pT1 carcinomas (P < 0.05). The marked differences in the frequency of all of the analyzed changes between pTa grade 1/grade 2 and pT1-4 carcinomas support the concept of these tumor groups representing different tumor entities.

High-throughput tissue microarray analysis of cyclin E gene amplification and overexpression in urinary bladder cancer.

Studies by comparative genomic hybridization revealed that the 19q13 chromosomal region is frequently amplified in bladder cancer. The cyclin E gene (CCNE), coding for a regulatory subunit of cyclin-dependent kinase 2, has been mapped to 19q13. To investigate the role of cyclin E alterations in bladder cancer, a tissue microarray of 2,317 specimens from 1,842 bladder cancer patients was constructed and analyzed for CCNE amplification by fluorescence in situ hybridization and for cyclin-E protein overexpression by immunohistochemistry. Fluorescence in situ hybridization analysis showed amplification in only 30 of the 1,561 evaluable tumors (1.9%). Amplification was significantly associated with stage and grade (P: < 0.0005 each). Immunohistochemically detectable cyclin E expression was strong in 233 (12.4%), weak in 354 (18.9%), and negative in 1, 286 of the 1,873 interpretable tumors. The majority (62.1%) of CCNE-amplified tumors were strongly immunohistochemistry-positive (P: < 0.0001). The frequency of protein expression increased from stage pTa (22.2%) to pT1 (45.5%; P: < 0.0001) but then decreased for stage pT2-4 (29.4%; P: < 0.0001 for pT1 versus pT2-4). Low cyclin E expression was associated with poor overall survival in all patients (P: < 0.0001), but had no prognostic impact independent of stage. It is concluded that cyclin E overexpression is characteristic to a subset of bladder carcinomas, especially at the stage of early invasion. This analysis of the prognostic impact of CCNE gene amplification and protein expression in >1,500 arrayed bladder cancers was accomplished in a period of 2 weeks, illustrating how the tissue microarray technology remarkably facilitates the evaluation of the clinical relevance of molecular alterations in cancer.

Response and palliation in a phase II trial of gemcitabine in hormone-refractory metastatic prostatic carcinoma. Swiss Group for Clinical Cancer Research (SAKK).

BACKGROUND: In a phase II trial, 43 patients with hormone-refractory prostate cancer were treated with gemcitabine at a dose of 1,200 mg/m2 over 2 hours (later decreased to 1,000 mg/m2 due to hematological toxicity) on days 1, 8 and 15 of a 28 day cycle. PATIENTS AND METHODS: Inclusion criteria were proven tumor progression after hormonal treatment and increased PSA levels, a WHO PS < or = 2, adequate bone marrow reserve, liver and renal function and age < or =, 80 years. Response criteria were based on PSA levels (CR: normalization of PSA, PR: > 50% decrease). Quality of life (QL) was assessed with the EORTC QLQ-C30 on day 1 of each treatment cycle and on day 8 of the first cycle (range of scales 0-100). Physician-rated pain intensity and use of pain medication were assessed at the same timepoints. RESULTS: Hematological toxicity of gemcitabine led to a dose-reduction in 48% of all cycles. Three of forty-three patients (RR = 7%) showed a PSA response: one CR and three PR with time to treatment failure of 8.7, 6.6 and > or = 9.3 months. Seven patients (16%) had stable disease (NC) for a median duration of 7.1 months (range 6.1-11.7 months). There was one case with objective regression of lymph node metastases. Patients reported a considerably impaired health status/QL (n = 41, median = 50) and severe fatigue (n = 41, median = 55.6) at baseline, with no change under treatment. Pain (QLQ-C30) was also severe at baseline (N=41, median=50) but was improved at the end of cycles 1 (n = 33, median change = -16.7, P = 0.0002), 2 (n = 19, median change = -33.3, P = 0.0006), 3 (n = 14, median change = -16.7, P = 0.06) and 4 (n = 9, median change = -33.3, P = 0.04). Patient-rated pain and use of analgesics as combined endpoint yielded palliation for at least 8 weeks in 14 patients (32%). Nine of these patients showed at least stable disease (CR/PR or NC by PSA level), five indicated a benefit in spite of progressive disease. CONCLUSIONS: Gemcitabine in the dose and schedule indicated above has a significant beneficial impact on pain in patients with hormone-refractory prostatic carcinoma despite its limited activity in terms of PSA response and considerable, especially hematological, toxicity.

Transitional cell carcinoma of the vagina with pagetoid spread pattern.

A distinctive variant of a papillary noninvasive transitional cell carcinoma (TCC) of the vagina removed from a postmenopausal woman is described. The neoplasm was evaluated by immunohistochemistry. The designation of this neoplasm as a TCC is supported by its morphological features and its coexpression for cytokeratin (CK) 7 and CK 20. Its main feature is pagetoid infiltration into adjacent vaginal epithelium. This is the second reported case involving a transitional cell metaplasia (TCM) of the vagina, a possible precursor lesion of the TCC.

A phase II study of oral idarubicin as a treatment for metastatic hormone-refractory prostate carcinoma with special focus on prostate specific antigen doubling time. Swiss Group for Clinical Cancer Research, Berne, Switzerland.

BACKGROUND: Treatment of hormone-refractory prostate carcinoma with chemotherapy is purely palliative, and reported response rates have been low. At the time this study was conducted, there was an urgent need for a trial using potentially efficacious drugs, with quality of life (QL), and serial prostate specific antigen (PSA) behavior as endpoints. METHODS: In this Swiss multicenter Phase II study, 30 patients were enrolled to receive oral idarubicin. Patients were administered 35 mg idarubicin on Days 1 and 8 of each cycle, and treatment was repeated every 3 weeks. Assessment was based on response rates, sequential PSA measurements in serum, toxicity, and selected aspects of QL. RESULTS: Twenty-six of 30 patients were evaluable for response, and none of them achieved a response. Three patients had stable disease as their best response, and their PSA levels also remained stable. In all other patients, PSA increased exponentially over time; the median PSA doubling time was 2.1 months (mean, 2.6; range, 0.7-6.1). Toxicity was minimal and consisted mainly of myelosuppression and nausea/vomiting. QL did not change significantly during therapy with regard to general well-being, fatigue, or nausea/vomiting. However, there were improvements in patient-rated and physician-rated pain. CONCLUSIONS: At the dose and schedule used in this study, oral idarubicin showed only minimal efficacy against hormone-refractory prostate carcinoma. In patients who did not respond, PSA doubling times were similar to those in patients who relapsed while receiving only antiandrogen therapy. In future clinical trials, QL and serial PSA behavior should be included in analysis.

Impact of minimal lymph node metastasis on long-term prognosis after radical prostatectomy.

OBJECTIVES: In the management of clinically localized prostate cancer, understanding is of major concern. There is a considerable therapeutic dilemma in those patients in whom staging lymphadenectomy prior to intended radical prostatectomy reveals lymph node metastases. METHODS: Pelvic lymph node dissection and radical retropubic prostatectomy were performed in 132 consecutive patients. Patients with extracapsular disease and/or positive lymph nodes received adjuvant radiotherapy. Median follow-up after surgery was 7 years and 2 months. To study the influence of minimal lymph node metastasis, category pN1 was further subdivided into pN1.1 and pN1.2. Involvement of the prostatic capsule was either classified as infiltration (pT3.1) or performation (pT3.2) of the capsule. RESULTS: Disease-free survival after 10 years was 58% in patients with negative nodes, 37% in category pN1.1, 25% in category pN1.2 and 10% in category pN2. Corrected overall survival was 83% for node-negative patients and 73% for category pN1.1, but it was only 33% for pN1.2 and 29% for pN2. Patients in category pT3.1 had a statistically significant better survival than those in pT3.2. CONCLUSIONS: We conclude that radical prostatectomy combined with adjuvant radiotherapy is a valuable option in prostate cancer patients with minimal lymph node metastasis. When compared to infiltration of the capsule, complete capsular perforation does adversely affect prognosis.

Isoelectric focusing of Tamm-Horsfall glycoproteins: a simple tool for recognizing recurrent calcium oxalate renal stone formers.

Tamm-Horsfall glycoproteins (THPs) from healthy probands and a majority of recurrent calcium oxalate renal stone formers reveal different physicochemical properties when analyzed using isoelectric focusing (IEF). The pI values of THPs from healthy probands are approximately 3.5 while THPs from recurrent renal stone formers have pI values of between 4.5 and 6. The two groups of THPs exhibit completely different protein patterns. The differences in IEF analysis allow differentiation between THPs from healthy probands and recurrent calcium oxalate stone formers and may possibly be used as a simple diagnostic method for the recognition of recurrent calcium oxalate renal stone formers.

Intracytoplasmic sperm injection (ICSI) with testicular sperm extraction (TESE) in non-obstructive azoospermia--two case reports.

Intracytoplasmic sperm injection (ICSI) with microsurgical epididymal sperm extraction (MESA) or testicular sperm extraction (TESE) can be offered to azoospermic men. We report our initial experience of two cases with ICSI-TESE in non-obstructive azoospermia. Both couples had a successful ICSI with embryo transfer. An ongoing triplet pregnancy at 21 weeks is observed.