Biomedical subjects
Publications and source records attributed to C A Hulsbergen-van de Kaa.
We investigated whether smoking is associated with mutations in the Von Hippel-Lindau (VHL) gene in 337 cases of sporadic renal cell carcinoma (RCC) among 120 852 people followed for 11.3 years; the findings suggest that smoking causes RCC independently of VHL gene mutations.
We report a young girl who died in an Addisonian crisis due to previously undiagnosed congenital adrenal hyperplasia (CAH), in whom ovarian adrenal rest tissue was detected at postmortem histopathological examination. This is a very rare complication in female patients with CAH with only two previously reported cases.
We describe a 35-year-old man who was initially treated with standard inguinal orchiectomy and prophylactic radiotherapy for Stage I seminomatous germ cell tumor of the testis. We report the case because of the unique nature of the later disease recurrence, which was a solitary cranial bony recurrence that extended both intracranially and extracranially. The patient had complete remission after combined cisplatin-based chemotherapy.
The classification of azoospermia into obstructive or non-obstructive is largely based on medical history, physical examination and biochemical markers in serum and semen. However, the most accurate parameter for diagnosis is the testicular histology. The predictive value of the percutaneous epididymal sperm aspiration (PESA), FSH, LH, testosterone, inhibin-B and testicular volume was investigated for their accuracy to predict a complete spermatogenesis (Johnsen score > or =8) in order to replace the testicular histology. The specificity and sensitivity of FSH, inhibin-B, LH, testosterone, testicular volume, and the presence of sperm in a PESA procedure was evaluated in 147 azoospermic males attending the centre for infertility diagnosis. A positive PESA outcome presented the highest sensitivity and specificity to predict a Johnsen score > or =8 (93 and 94% respectively) compared with FSH (90 and 19%), inhibin-B (88 and 57%) and testicular volume (95 and 45%). Differences in clinical presentation were observed between patients with positive sperm retrieval with PESA, depending on the aetiology of obstruction. In conclusion, the presence of spermatozoa in the epididymis (PESA+) correlates with a Johnsen score > or =8 and is the most accurate parameter to predict complete spermatogenesis compared with clinical or biochemical parameters. Between obstructive azoospermic patients, the clinical parameters observed varied according to the aetiology.
OBJECTIVES: To compare retrospectively the treatment results of surveillance and primary retroperitoneal lymph node dissection (RPLND) of patients with clinical Stage I nonseminomatous germ cell tumors of the testis (NSGCT) in two institutions in The Netherlands. METHODS: From 1982 to 1994, 90 consecutive patients with clinical Stage I NSGCT were prospectively entered in a surveillance protocol in Amsterdam (group 1). In the same period, 101 patients with clinical Stage I NSGCT underwent primary RPLND in Nijmegen (group 2). Both patient populations were comparable for patient age, presence of vascular invasion, and embryonal cell components in the primary tumor. All patients in group 1 with relapse, except for 2, were treated with cisplatin-based chemotherapy. All patients in group 2 with vital tumor in the RPLND specimen were treated with two adjuvant courses of combined chemotherapy (cisplatin, etoposide, and bleomycin). RESULTS: In group 1, at a median follow-up of 7.7 years, 23 patients (26%) had relapse. The median time to relapse was 12 months. Relapses were located retroperitoneally (n = 18, 78%), in the lung (n = 3, 13%), scrotally (n = 1, 4%), and combined in the liver, lung, and pleura (n = 1, 4%). After treatment of relapses (chemotherapy in 21 and/or surgery in 11), only 1 patient died of disseminated disease. A disease-free survival rate of 98.5% was achieved at the median follow-up. The main toxicities consisted of short-lasting leukopenia, accompanied by infection (13%). Four patients reported cardiovascular and four neuropathy complaints. In group 2, the median follow-up was 6.9 years. In 31 patients (30.7%), vital tumor was found retroperitoneally; after two courses of combined chemotherapy, none of them had a relapse. Seven patients with pathologic Stage I disease (6.4%) had a pulmonary relapse within 1 year after surgery. No retroperitoneal relapses were found. After chemotherapy, 6 patients with relapse were salvaged, and 1 died of disseminated disease. The disease-specific survival rate in group 2 was 98% at the median follow-up. The most frequent surgical complications were lymphocele (n = 3), small bowel obstruction (n = 3), and abdominal pain (n = 3). The antegrade ejaculation rate was 94%. CONCLUSIONS: Excellent treatment results in terms of disease-free survival can be achieved in Stage I NSGCT with both surveillance and primary RPLND. Patients with pathologic Stage II disease adjuvantly treated with chemotherapy did not have any relapse and consequently all survived. Most complications after both treatment strategies are reversible. The choice of treatment should be based on balanced information and not on dogmatic principles.
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Within normal human prostate epithelium, basal and luminal cells can be discriminated by their expression of keratins (K). While basal cells express K5/14, luminal cells show expression of K8/18 and an intermediate cell population can be identified by co-expression of K5/18. Prostate cancer is predominantly composed of luminal and neuroendocrine cells, while a minority of cells have a basal phenotype. In order to distinguish between basal and intermediate cells, and to assess the effects of androgen deprivation on prostate cancer, 56 human prostate cancer metastases and three cancer cell lines were characterized using antibodies to K5, K14, K18, and the neuroendocrine marker chromogranin A (ChA). The staining was performed on paraffin tissue and visualized by the avidin-biotin-peroxidase complex method. Protein expression was quantified as the number of positive cells in 20 high power fields (HPF; 400x). Keratin expression in the prostate cancer cell lines LNCaP, DU145, and PC3 was analysed by immunofluorescence with triple staining and confocal laser scanning microscopy. Prostate cancer metastases were consistently positive for K18 and negative for K14, irrespective of hormonal therapy. K5 expression was displayed in 28.9% of the tumours without treatment, in 75% after androgen deprivation, and in 57.1% of hormone-escaped prostate carcinomas. After androgen deprivation, the number of K5-expressing cells increased significantly. While androgen-dependent prostate cancer showed a median of 0 cells/20 HPF (range 0-50), regressed tumours displayed 22.5 (range 0-65) and hormone-escaped tumours 7.5 (range 0-361) positive cells/20 HPF. Expression of ChA was observed in 47.4% of the androgen-dependent tumours. The number of neuroendocrine cells was not significantly affected in regressed or hormone-escaped disease. The androgen-dependent cell line LNCaP stained for K18, while the androgen-independent lines DU145 and PC3 both expressed K5 and 18. Expression of K5 in the absence of K14 identifies the existence of an intermediate cell population in prostate carcinoma. Accumulation of intermediate cells in regressed and hormone-escaped prostate cancer indicates that for their survival, these cells are androgen-independent.
OBJECTIVES: To compare the accuracy of the detection, localization, and staging of prostate cancer using transrectal three-dimensional (3D) grayscale ultrasonography (3D-US) with conventional transrectal two-dimensional grayscale ultrasonography (2D-US). METHODS: Fifty patients with clinical localized prostate cancer scheduled to undergo radical retropubic prostatectomy and 50 patients with clinical benign prostatic hyperplasia underwent transrectal ultrasound investigations (2D and 3D). The prostate images were retrospectively analyzed by two ultrasound experts unaware of the clinical findings. The images of the prostate cancer group were correlated with the whole-mount histologic specimens of the prostate. RESULTS: All percentages are given for experts 1 and 2. The sensitivity, specificity, and accuracy for the detection of prostate cancer without considering the definitive localization of the tumor for 2D-US was 72% and 76%, 50% and 54%, and 63% and 64%, respectively; for 3D-US, the rates were 82% and 88%, 40% and 42%, and 61% and 65%. The sensitivity, specificity, and accuracy of the combination of 2D-US with 3D-US was 88% and 90%, 36% and 38%, and 62% and 64%, respectively. The sensitivity, specificity, and accuracy for the exact localization of the prostate tumor for 2D-US was 44% and 46%, 50% and 54%, and 47% and 50%, respectively; for 3D-US, they were 52% and 62%, 40% and 42%, and 46% and 52%. The staging of prostate cancer using 3D-US was correct in 49% (expert 1) and in 57% (expert 2) of patients. No difference was observed between 2D-US and 3D-US for accurate staging. Both experts judged the interpretation of 3D-US images as superior to that of 2D-US images. CONCLUSIONS: Although 3D-US had statistically significant increased sensitivity in the detection of lesions and decreased specificity compared with 2D-US, 3D-US did not result in significant clinical improvement in the detection and staging of prostate cancer.
OBJECTIVE: Increased microvessel density (MVD) of prostate cancer seems to be associated with poor prognosis and higher stage. Assessment of MVD using noninvasive methods could be of use in the work-up of patients with prostate cancer. The aim of the present study was to correlate three-dimensional contrast-enhanced power Doppler ultrasound (3D-CE-PDU) findings with MVD characteristics of radical prostatectomy specimens. METHODS: Seven patients with biopsy-proven prostate cancer had 3D-CE-PDU investigations 2-3 weeks after prostate biopsies were taken and prior to radical prostatectomy. The investigations were performed using Levovist contrast agent (Schering AG, Berlin, Germany) in combination with a Voluson 530D ultrasound scanner (Kretz AG, Zipf, Austria). The 7 patients were selected because of lateralization of the contrast enhancement. Histology slides were made of the side with 'contrast enhancement' and of the contralateral 'unenhanced' side and stained according to the catalyzed reporter deposition (CARD) amplification procedure, and MVD parameters were obtained. RESULTS: In all patients the MVD count of the 'enhanced' side was higher than the MVD count of the 'unenhanced' side, averaging 1.93 times higher. On histology all enhanced lesions proved to contain prostate cancer tissue (average maximum diameter 25 mm (range 17-31)). Two patients had a small bilateral tumor lesion (4 and 5 mm respectively) and in total 5 patients had even smaller satellite lesions (1-2 mm). The smaller lesions were not identified using 3D-CE-PDU. CONCLUSIONS: The present study shows that 3D power Doppler contrast ultrasonography is a minimally invasive imaging modality, which has the potential to visualize lesions with increased MVD. This property of 3D-CE-PDU could be used in the detection of prostate cancer.
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Comparative genomic hybridization analysis of a primary osteosarcoma and its metastasis revealed two regions of DNA amplification, one at 17p11.2-12 and one at 19q12-13. Subsequent representational difference analysis of the primary tumor resulted in the isolation of two distinct tumor-amplified DNA fragments originating from chromosome 19. A YAC clone corresponding to one of the two isolated DNA fragments was used for fluorescence in situ hybridization on normal human lymphocyte metaphases and tumor-derived nuclei. This resulted in the localization of this YAC to 19q12-13.1 and confirmed the amplification status of the isolated fragment in the tumors. The availability of such RDA-isolated sequences may be instrumental in the search for genes relevant for tumor development.
Renal failure in the newborn infant is mainly determined by vascular causes. In this report we describe a patient with a particular vascular cause of renal failure. The patient was the product of a twin pregnancy in which the twin partner died in utero. In retrospect, the twins appeared to be monozygotic. As the pregnancy was studied carefully prenatally by ultrasound, we were able to observe the development of this condition, characterized by oliguria, oligohydramnios, and lung hypoplasia: the oligohydramnios sequence. After organ development had been normal initially, renal function was lost and the oligohydramnios sequence developed in the survivor after the co-twin had died in utero.