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Biomedical subjects

W Tjalma

Publications and source records attributed to W Tjalma.

At least 19 recordsLinked to original sources

Endometrial safety after 5 years of continuous combined transdermal estrogen and intrauterine levonorgestrel delivery for postmenopausal hormone substitution.

OBJECTIVE: To investigate endometrial histology and thickness of the endometrium after long-term use of continuous transdermal estrogen substitution combined with intrauterine release of levonorgestrel (LNG) in postmenopausal women. DESIGN: A 5-year non-comparative prospective clinical trial. SUBJECTS: Out of 182 symptomatic postmenopausal women using estrogen substitution therapy (EST) combined with a novel T-shaped LNG-releasing intrauterine system (Femilis Slim LNG-IUS), to prevent endometrial proliferation and bleeding, only those women (n=102) who used two consecutive LNG-IUSs, were isolated with the aim to study the long-term effects on the endometrium. The mean age of the women was 57 years (range 47-71). The majority of women received percutaneous 17beta estradiol, 1.5mg daily, or an equivalent dose by patch or orally, on a continuous basis. MAIN OUTCOME MEASURES: Endometrial histology and ultrasonographic evidence of endometrial suppression, after a period of approximately 5 years of use. The mean duration of use of the regimen was 70 months (range 25-98). RESULTS: The dominant endometrial histologic picture was that of inactive endometrium characterized by glandular atrophy and stroma decidualization (Kurman classification 5b). No cases of endometrial hyperplasia were found. On transvaginal ultrasound, this corresponds with a thin endometrium (< or = 5 mm). CONCLUSION: The results of this 5-year study in 102 postmenopausal women using EST demonstrates that the LNG-IUS effectively opposes the estrogenic effect on the endometrium resulting in strong suppression during the entire period of EST. Due to its high efficacy and absence of systemic effects on organ tissues (e.g., breasts), target delivery in the uterine cavity could be a preferred route to administer a progestagen in women using EST.

Administration, Cutaneous↗

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↗

Magnetic resonance imaging in breast cancer.

AIM: Due to its high sensitivity, magnetic resonance (MR) mammography is increasingly used as adjunct to mammography and ultrasound. The technique, however, has a relatively limited specificity. Therefore, it may only be used for specific indications. One of the indications is preoperative staging of breast carcinoma. This review serves to give an overview of the studies published on the role of MR in preoperative local staging. METHODS: We reviewed studies of the role of MR mammography in the detection of breast carcinomas and in the assessment of the diameter and extent of carcinomas. We also reviewed published studies on detection of multifocal and multicentric carcinomas that were occult on mammography and ultrasound. Advantages and drawbacks of preoperative MR mammography and the effect on treatment, as reported in different published studies, are described. The review is based on a search of PubMed, using specific terms for the different topics. RESULTS: MR has the highest sensitivity to detect invasive carcinomas and is best in assessment of tumor extent, including detection of multifocal, multicentric and bilateral disease. CONCLUSION: MR mammography is a valuable adjunct to conventional imaging in the preoperative local staging of breast cancer.

Breast Neoplasms↗

Postpartum hemorrhage: practical approach to a life-threatening complication.

Postpartum haemorrhage (PPH) occurs in 5% of all deliveries and is responsible for a major part of maternal mortality. Adequate attendance to this complication can mean the difference between life and death. A well-trained staff together with clear and simple guidelines can make a significant difference to the patient. The aim of this article is to offer a practical guide for the management of PPH; a flowchart is presented. When faced with refractory hemorrhage, one can switch to interventional therapy or surgery. Efficiency and speed play a key part in the approach to this life threatening bleeding.

Female↗

Preoperative breast MRI in patients with invasive lobular breast cancer.

To investigate the use of MRI in preoperative characterization of invasive lobular breast cancer (ILC) and in detection of multifocal/multicentric disease. We retrospectively reviewed T1-weighted FLASH 3D precontrast and postcontrast MR images together with subtraction images of 26 women with histopathologically proven invasive lobular cancer. Two experienced radiologists described tumor patterns of ILC independently. MR findings of unifocal, multifocal, single quadrant and multiquadrant disease were correlated with results of other imaging techniques and compared with histopathological findings as gold standard. Most ILC presented on MRI as a single spiculated/irregular, inhomogeneous mass (pattern 1, n=12) or as a dominant lesion surrounded by multiple small enhancing foci (pattern 2, n=8). Multiple small enhancing foci with interconnecting enhancing strands (pattern 3) and an architectural distortion (pattern 4) were both described in three cases. There was one case of a focal area of inhomogeneous enhancement (pattern 5) and one normal MR examination (pattern 6). Unifocal and multifocal lesions were identified on MRI in four patients with normal conventional imaging. In nine women, multiple additional lesions or more extensive multiquadrant disease were correctly identified only on MRI. MRI may play an important role in the evaluation of patients with ILC, which is often difficult to diagnose on clinical examination and conventional imaging and more likely occur in multiple sites and in both breasts. However, false-negative MR findings do occur in a small percentage of ILC.

Adult↗

Contrast-enhanced MR imaging of breast lesions and effect on treatment.

PURPOSE: To assess the value of local staging with preoperative magnetic resonance imaging (MRI) in patients with suspect breast lesions and the effect on therapeutic approach. MATERIALS AND METHODS: Two hundred and four consecutive women with suspect breast lesions on clinical examination (CE) and/or mammography (MX) and/or ultrasound (US) underwent preoperative contrast-enhanced MRI. Detection of multifocal, multicentric and bilateral breast cancer by all three imaging modalities was evaluated. Results of preoperative breast MRI were discussed with the treating surgeons. The type of therapeutic change after preoperative MRI was marked on a questionnaire (none, additional fine needle aspiration, core biopsy, open biopsy, wider excision, mastectomy) and considered 'necessary' or 'unnecessary' using final histopathological results as gold standard. RESULTS: In 170 patients, breast cancer was diagnosed. MRI detected 96% of multifocal disease and 95% of multicentric disease, whereas MX depicted 37 and 18%, and US 41 and 9% of them, respectively. All bilateral breast cancers were seen on MRI; both MX and US detected 56%. Findings of more extensive disease and unsuspected multiple breast cancer foci identified on MRI only, changed the therapeutic approach correctly in 30.6% of breast cancer patients. Nine unnecessary wider excisions and three unnecessary FNA/core biopsies were performed because MRI overestimated the number or size of malignant lesions. CONCLUSION: Preoperative breast MRI is an important adjunct to conventional imaging in the loco-regional staging of breast cancer and a useful tool in treatment planning.

Adult↗

The correlation of preoperative CT, MR imaging, and clinical staging (FIGO) with histopathology findings in primary cervical carcinoma.

The aim of this study was to compare the preoperative findings of abdominal/pelvic CT and MRI with the preoperative clinical International Federation of Obstetrics and Gynecology (FIGO) staging and postoperative pathology report in patients with primary cancer of the cervix. Thirty-six patients with surgical-pathological proven primary cancer of the cervix were retrospectively studied for preoperative staging by clinical examination, CT, and MR imaging. Studied parameters for preoperative staging were the presence of tumor, tumor extension into the parametrial tissue, pelvic wall, adjacent organs, and lymph nodes. The CT was performed in 32 patients and MRI (T1- and T2-weighted images) in 29 patients. The CT and MR staging were based on the FIGO staging system. Results were compared with histological findings. The group is consisted of stage 0 (in situ):1, Ia:1, Ib:8, IIa:2, IIb:12, IIIa:4, IVa:6, and IVb:2 patients. The overall accuracy of staging for clinical examination, CT, and MRI was 47, 53, and 86%, respectively. The MRI incorrectly staged 2 patients and did not visualize only two tumors; one was an in situ (stage-0) and one stage-Ia (microscopic) disease. The MRI is more accurate than CT and they are both superior to clinical examination in evaluating the locoregional extension and preoperative staging of primary cancer of the cervix.

Adult↗

Folate and Vitamin B(12) deficiency presenting as pancytopenia in pregnancy: a case report and review of the literature.

We present a case of extreme pancytopenia in a 27-year-old pregnant woman. The initial picture was compatible with a severe hematological problem in the category of aplastic anemia, paroxysmal nocturnal hemoglobinuria or even acute leukemia. The further biochemical investigations revealed, however, a folate deficiency. Nowadays this is a very rare cause of pancytopenia. Next to this she also had a Vitamin B(12) deficiency due to intrinsic factor failure. The recent literature is discussed.

Adult↗

The evaluation of proliferative activity in CIN III and microinvasive cervical cancer and its role in recurrence.

OBJECTIVE: To evaluate the proliferation activity in CIN III lesions and Ia1 carcinoma according to the risk of recurrence. STUDY DESIGN: The proliferation markers PCNA (proliferating cell nuclear antigen) and mitotic index were studied in 75 patients with CIN III and in 20 patients with an Ia1 squamous carcinoma of the cervix by staining representative tissue sections for the PCNA and assessing the mitotic index. Associations between the studied proliferation markers and various histopathologic characteristics as well as recurrence were assessed. RESULTS: Three groups of PCNA were constituted: <20, 20--40, > OR =40% positive tumour nuclei, which contained, respectively, 45 (47%), 29 (31%), and 21 (22%) patients. Microinvasive carcinomas have a higher proliferation activity than CIN III (PCNA P=0.005; mitotic index P=0.094). For CIN III, there was a significantly lower risk for recurrence in the group with lower mitotic activity, compared to the group with higher mitotic activity (Kaplan-Meier: log-rank testing P=0.044). Significance was, however, not reached for the different PCNA categories (Kaplan-Meier, log-rank test P=0.068). Multiple regression analysis showed that in our population of CIN III lesions, only age of diagnosis and treatment modality were relevant (independent) prognostic indicators for recurrence. CONCLUSIONS: In CIN III lesions there is evidence for an association between proliferation activity and the risk of recurrence. The observed crude association weakens when adjusting for age at diagnosis and treatment modality. Apparently this feature is associated with more aggressive biological behaviour and could be used to identify women who are at higher risk of recurrence.

Adult↗

The association between vascular endothelial growth factor, microvessel density and clinicopathological features in invasive cervical cancer.

OBJECTIVE: The aim of this study was to analyse the vascular endothelial growth factor (VEGF) expression in a series of cervical carcinomas and to compare the results with the microvessel density (MVD) and clinicopathological features. STUDY DESIGN: The immunoreactivity for VEGF was studied in 130 invasive cervical carcinomas and in 22 patients with a carcinoma in situ of the cervix. The results were compared with the MVD. RESULTS: Staining for VEGF of less then 50% per slide occurred in 80% of the invasive carcinomas and in 82% of the in situ carcinomas. The median MVD was 261 vv/mm(2) (range: 11-1000) in the invasive group and 146 vv/mm(2) (range: 25-536) in the in situ group. Unlike the microvessel density there was no association between VEGF expression and survival. The MVD was higher in VEGF poorer (<50%) tumours (P=0.055). Beside tumour histology (P=0.012) there were no other significant relationships between the remaining histopathological findings and VEGF expression. CONCLUSION: Tissue VEGF expression has no prognostic value in contrast with the MVD in patients with invasive cervical cancer.

Adenocarcinoma↗

[Primary malignant melanoma of the female urethra].

Primary malignant melanomas of the urethra are extremely rare. Clinically they are usually mistaken for other malignant diseases or even benign lesions. The case of a 66-year-old woman is reported, who presented with local bleeding of the urethra. Macroscopically a polypoid tumor was seen on the meatus externus of the urethra. A biopsy was taken and the histology report revealed a malignant melanoma. There were no signs of metastases and therefore the treatment consisted of a wide local excision only. A review of literature regarding therapy and prognosis is presented.

Aged↗

Neoadjuvant chemotherapy versus primary debulking surgery in advanced ovarian cancer.

Primary surgical cytoreduction followed by chemotherapy usually is the preferred management of advanced (stage III or IV) ovarian cancer. The presence of residual disease after surgery is one of the most important adverse prognostic factors for survival. Neoadjuvant chemotherapy has been proposed as an alternative approach to conventional surgery as initial management of bulky ovarian cancer, with the goal of improving surgical quality. Since 1989, we have been treating advanced epithelial ovarian cancer with neoadjuvant chemotherapy instead of primary cytoreductive surgery in approximately half of the patients with stage III-IV disease. Selection of neoadjuvant chemotherapy was based on disease-related characteristics (eg, metastatic tumor load, stage of disease, performance status). Since 1993, open laparoscopy also has been used to aid in evaluating operability. A retrospective analysis of 338 patients was conducted to compare outcomes during 1989 to 1998, when neoadjuvant chemotherapy was used, with those observed during 1980 to 1988, when all patients underwent primary cytoreductive surgery. Crude 3-year survival rates were higher and postoperative mortality rates were lower during the second time period compared with the first. Overall, the results suggest that neoadjuvant chemotherapy results in survival rates in selected patients with advanced ovarian cancer that are comparable with those associated with primary cytoreductive surgery. Patients with stage IV disease, total metastatic tumor load greater than 1,000 g, uncountable plaque-shaped peritoneal metastases, and/or a poor performance status are probably the best candidates for this alternative approach. A prospective randomized study of neoadjuvant chemotherapy and primary cytoreductive surgery is ongoing.

Adult↗

Validation of nuclear texture, density, morphometry and tissue syntactic structure analysis as prognosticators of cervical carcinoma.

OBJECTIVE: To evaluate the performance of karyometry and histometry in the prediction of survival, recurrence and response of early-stage invasive cervical carcinoma. STUDY DESIGN: Nuclear morphometry, chromatin texture and tissue architecture (characterized by syntactic structure analysis) were measured using a semiautomated image analysis system on 46 cases of Feulgen-stained tissue sections. The performance of the features was compared to that of clinical features, reported to be the best prognosticators until now, such as age, lympho-vascular permeation, histologic type, stage and grade. A K nearest neighbor classifier was used for classification. RESULTS: In the prediction of three-year survival, recurrence and response, syntactic structure analysis proved to be the best performer. Classification rates were, respectively, 100%, 94.4% and 94.5%. In all classifications, karyometric and histometric features outperformed clinical features. In general, the best performing features described differences in second-order population statistics (standard deviations). CONCLUSION: The results show that a quantitative analysis based on nuclear morphology, chromatin texture and histology can be considered an excellent aid in the prognosis of invasive cervical carcinoma. The measurements are not hampered by the need to undertake complete resections and are suited to daily practice when implemented in a semiautomated image analysis system.

Adult↗

Angiogenesis in cervical intraepithelial neoplasia and the risk of recurrence.

OBJECTIVE: We sought to investigate whether angiogenesis can predict the risk of recurrence of cervical intraepithelial neoplasia after treatment. STUDY DESIGN: Microvessel density was studied in 75 patients with grade 3 cervical intraepithelial neoplasia and in 20 patients with microinvasive squamous carcinoma (International Federation of Gynecology and Obstetrics stage IA1) of the uterine cervix by staining representative tissue sections with the specific endothelial marker anti-CD31. The microvessel density was determined with a digital image analyzer. The results were correlated with clinical and histopathologic data. RESULTS: The mean vessel density was 264 per field (range, 86-674 per field) in grade 3 cervical intraepithelial neoplasia and 378 per field (range, 161-848 per field; P = .001) in microinvasive squamous carcinoma. Thirteen patients with grade 3 cervical intraepithelial neoplasia had recurrent cervical intraepithelial neoplasia (microvessel density, recurrent vs nonrecurrent; not significant). Multiple regression analysis in the noninvasive group confirmed that the mean vessel density (P = .121) had no prognostic value. Furthermore, it showed that the age at diagnosis (P = .011), menopausal status (P = .052), and treatment modality (P = .022) proved to be independent prognostic factors for recurrence. CONCLUSIONS: During the progression from noninvasive to microinvasive cervical carcinoma, the microvessel density increases significantly. However, the vessel density does not predict recurrence of noninvasive lesions.

Adult↗

Chest wall resection for local recurrence of breast cancer. Presented at the 99th Meeting of the Royal Belgium Society of Obstetrics and Gynecology, Brussels May 9th 1998, Belgium.

We present three cases of chest wall resection for locally recurrent breast cancer and a Medline review of the current literature. In selected cases full thickness resection of the chest wall may be used as a salvage procedure to improve the quality of life and prolong the survival at low morbidity and mortality.

Adult↗

Prenatal diagnosis of a constitutional interstitial deletion of chromosome 5 (q15q31.1) presenting with features of congenital contractural arachnodactyly.

Prenatal diagnosis of a constitutional interstitial deletion of chromosome 5 (q15q31.1) in a 30-year-old woman is reported. At 21 weeks of pregnancy, routine fetal ultrasounds showed the presence of apparently isolated bilateral club feet. Fetal karyotyping documented an interstitial deletion of the long arm of chromosome 5: 46,XX,del(5) (q15q31) in all 50 analyzed metaphases. Because such deletion is associated with severe psychomotor retardation, the pregnancy was terminated. Postmortem karyotyping of skin fibroblasts confirmed the presence of this interstitial de novo deletion in all mitoses. The breakpoints on 5q were analyzed by fluorescent in situ hybridization and were localized at 5q15 and q31.1. This case illustrates the importance of fetal karyotyping in cases of isolated club feet. At autopsy, the fetus presented had minor anomalies and contractures of knee and hip joints. These clinical findings could fit the diagnosis of congenital contractural arachnodactyly (CCA) or Beals syndrome. CCA is caused by a defect in the fibrillin-2 (FBN2) gene. This gene was previously mapped on 5q23-31. Our molecular studies of both parents and the fetus, using an intragenic polymorphic GT repeat, showed that the FBN2 gene was deleted in the fetus and that the de novo interstitial deletion occurred on the paternally inherited chromosome 5. Thus, CCA may be caused by a loss of function of the FBN2 gene. Clinical findings in this fetus and those of other described cases with interstitial 5q deletions are reviewed, and similarities with CCA are stressed.

Abnormalities, Multiple↗