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Biomedical subjects

P van Diest

Publications and source records attributed to P van Diest.

10 recordsLinked to original sources
PubMed2006

Alterations in the p53 pathway and prognosis in advanced ovarian cancer: a multi-factorial analysis of the EORTC Gynaecological Cancer group (study 55865).

PURPOSE: The study was designed to determine independent prognostic variables in suboptimally debulked advanced ovarian cancer patients entered in the randomised phase III study EORTC 55865. EXPERIMENTAL DESIGN: Retrospectively collected paraffin blocks from 169 patients with stages IIb-IV epithelial ovarian cancer, taken at primary debulking surgery, were analysed. All patients were treated with cyclophosphamide and cisplatin (CP), and followed up for a median of 10 years. Expression of p53, bcl-2, P21, Ki-67 and HER-2 status was assessed by immunohistochemistry (IHC). RESULTS: Expression of p21, a downstream effector of the p53 gene, was found to be a favourable prognostic factor for survival (HR 0.58, CI 0.36-0.94, p=0.025) in addition to FIGO stage (HR 1.54, CI 1.08-2.21, p=or<0.02). For progression free survival (PFS), both p21 (HR 0.52) and Ki-67 (HR 0.6) were significant factors. CONCLUSION: P21 overexpression is a positive prognostic factor for survival and PFS in advanced ovarian carcinoma with residual lesions of more than 1 cm.

Adult↗
PubMed2002

Cyclin A is a prognostic indicator in early stage breast cancer with and without tamoxifen treatment.

Overexpression of G1-S regulators cyclin D1 or cyclin A is frequently observed in breast cancer and is also to result in ligand-independent activation of oestrogen receptor in vitro. This might therefore, provide a mechanism for failure of tamoxifen treatment. We examined by immunohistochemical staining the effect of deregulation of these, and other cell cycle regulators on tamoxifen treatment in a group of 394 patients with early stage breast cancer. In univariate analysis, expression of cyclin A, Neu, Ki-67 index, and lack of OR expression were significantly associated with worse prognosis. When adjusted by the clinical model (for lymph node status, age, performance status, T-classification, grade, prior surgery, oestrogen receptor status and tamoxifen use), only overexpression of cyclin A and Neu were significantly associated with worse prognosis with hazard ratios of, respectively, 1.709 (P=0.0195) and 1.884 (P=0.0151). Overexpression of cyclin A was found in 86 out of the 201 OR-positive cases treated with tamoxifen, and was the only independent marker associated with worse prognosis (hazard ratio 2.024, P=0.0462). In conclusion, cyclin A is an independent predictor of recurrence of early stage breast cancer and is as such a marker for response in patients treated with tamoxifen.

Aged↗
PubMed2001

Reconstruction after total en bloc sacrectomy for osteosarcoma using a custom-made prosthesis: a technical note.

STUDY DESIGN: A report of an innovative technique to restore the lumbosacral junction after resection of primary highly malignant osteosarcoma of the sacrum involving the whole sacrum, soft tissues, and adjacent posterior parts of both iliac wings. OBJECTIVES: To describe the planning and design of a custom-made sacral prosthesis, the surgical technique, and clinical and functional outcome of the patient. SUMMARY OF BACKGROUND DATA: Although there have been case reports about reconstruction methods after total sacrectomy, to date, there has not been a reported clinical case of successful reconstruction using an individual designed prosthesis based on a three-dimensional real-sized model. METHODS: A 42-year-old woman was referred with progressive neurologic impairment due to primary osteosarcoma of the sacrum invading surrounding structures. Based on a three-dimensional real-sized model, a detailed surgical plan was developed to assure safe, wide surgical margins. In addition, the model enabled design and testing of a custom-made sacral prosthesis, to provide stable lumbosacral reconstruction. RESULTS: After induction chemotherapy, a staged anteroposterior resection-reconstruction was successfully performed. After surgery, a superficial wound dehiscence was promptly treated. Within 3 weeks after surgery, mobilization began, and the adjuvant chemotherapy was continued. At the 36-month follow-up, the patient was disease free, had a stable, painless spinopelvic junction, and could walk short distances using ankle orthoses and crutches. Radiographs show complete incorporation of the pelvic grafts and unchanged position of the implant. CONCLUSIONS: In planning and performing a total sacrectomy, including substantial parts of iliac wings, a three-dimensional real-sized model offers surgeons distinct advantages. Wide bony resection margins can be drawn on the model, and an individual custom-made prosthesis to re-establish spinopelvic continuity can be designed and tested before the intervention.

Adult↗
PubMed2001

New chromosomal regions with high-level amplifications in squamous cell carcinomas of the larynx and pharynx, identified by comparative genomic hybridization.

Squamous cell carcinomas of the head and neck generally exhibit complex karyotypes. To gain better knowledge of the changes in the subgroup of laryngeal and pharyngeal squamous cell carcinoma, chromosomal gains and losses were investigated in 42 predominantly late-stage tumours, using comparative genomic hybridization. On average, 11.2 gains and 6.8 losses were found. Gains were detected in high frequencies at 1q, 3q, 5p, 7q, 8q, 11q13, 17q, and 18p, and losses at 3p, 4p, 5q, 11qter, and 18q. Neither the number nor the type of abnormalities, nor the occurrence of specific chromosome changes, was found to be related to DNA ploidy, tumour stage, or degree of differentiation. Apart from low-level gains, many high-level amplifications were identified, in particular 3q24-qter (15 cases). Other regions recurrently involved were 11q13 (7 cases), 18p (5 cases), 18q11.2 (4 cases), and 8q23-24 and 11q14-22 (3 cases). Many of these amplified regions have not been reported before. Over half of all loci harbour genes coding for growth factors and growth factor receptors, suggesting an important role for such genes in squamous cell tumourigenesis and in the progression of late-stage tumours.

Adult↗
PubMed1996

Standardized mitotic counts in breast cancer. Evaluation of the method.

Twenty-one pathologists and technicians participated in a study evaluating the variation present in mitotic counts for prognostication of breast cancer. The participants counted the mitotic figures in 20 breast cancer samples from ten high power fields (mitotic activity index, MAI, giving the results in mitotic figures per 10 fields) and also made a correction for field size and area fraction of the neoplastic epithelium to get the standardized mitotic index (volume fraction corrected mitotic index, or M/VV index, giving the result in mitotic figures per square mm of neoplastic epithelium). The difference in variation between the two methods was not big, but the standardized mitotic index (SMI) showed consistently smaller variation among all participants and different subgroups. Experienced pathologists had the highest variation in mitotic counts, and specially trained technicians, the lowest. The efficiency of the mitotic counts in grading (the grading efficiency) was used to evaluate the mitotic counts. In groups without special training for mitotic counts the mean grading efficiency was lower (experienced and training pathologists both on average had the potential to grade 88% of the cases correctly) than in the group specially trained for the purpose (trained technicians had the potential to grade 95% of the cases correctly). Among the specially trained technicians, the grading efficiency was of the same magnitude as the grading efficiency achieved in determining the S-Phase fraction of cells from paraffin embedded breast cancers by flow cytometry in different laboratories. The results suggest that special training is helpful in making mitotic counts more reproducible, and that in trained hands, the mitotic counts give results comparable to more sophisticated methods of determining proliferative activity in breast cancer.

Breast Neoplasms↗
PubMed1993

Prognostic importance of DNA flow cytometric variables in rhabdomyosarcomas.

AIM: To determine whether DNA ploidy patterns and S phase fraction offer prognostic information in patients with rhabdomyosarcoma (RMS). METHODS: DNA flow cytometry was performed on formalin fixed, paraffin wax embedded samples from primary tumours, and metastatic deposits or recurrences in 70 patients. DNA histogram analysis was done using a semi-automated cell cycle analysis program. RESULTS: Of the 70 primary tumours, 23 were DNA diploid, 32 DNA aneuploid, eight DNA multiploid, and seven DNA tetraploid. The prognosis for DNA aneuploid patterns was favourable, intermediate within the group of DNA tetraploid tumours and poor among patients with DNA diploid and DNA multiploid tumours (p = 0.009). In multivariate analysis (Cox regression model) DNA ploidy was an important independent prognostic factor, along with TNM stage, localisation, and histopathological classification. Ten out of 32 patients with a high S phase fraction (> 15%) with primary RMS achieved long term survival in contrast to 20 out of 29 patients with a low S phase fraction (< or = 15%) (p = 0.008). In 24 cases the DNA ploidy of cases of relapse was analysed. Of the 15 cases, in which stem line changes had occurred, 13 died of disease. No stem line changes were noted in nine cases and in this group four patients died of disease (p = 0.02). CONCLUSIONS: Assessment of DNA ploidy and S phase fraction in primary RMS and evaluation of stem line changes in cases of relapse are important variables in predicting prognosis.

Adolescent↗
PubMedDate not supplied

Endonasal venular permeability in rats exposed to the cold.

Sixteen rats were killed 22 hrs after being injected with a dose of 4 mCi(198)Au mixed with 16 mg of inert colloidal gold/100g body wt. The anterior nasal mucosa of the septum and turbinates in 10 rats which were injected and kept in a temperature of 5-7 degrees C showed mean radioactive counts 2-3 times higher than those recorded in the same areas in 6 control rats kept in ordinary room temperature (22 degrees C). In all sixteen rats the highest counts were obtained in the RES organs, namely the liver, spleen, adrenals and the bone marrow, in descending order. Other tissues revealed no significant radioactivity except for minor counts in the lungs and kidneys. The importance of these findings regarding the localisation of granulomatous diseases and vasculitis in the nose is discussed.

Animals↗