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ABSTRACT: The aim of the study was to investigate the role of 2-[fluorine-18]-fluoro-2-deoxy-d-glucose positron emission tomography (FDG PET) in the diagnosis of recurrent ovarian cancer.
One hundred six FDG PET scans performed in 54 patients in the follow-up after cytoreductive surgery and chemotherapy of ovarian cancer were reevaluated. Fifty-eight scans were performed in patients with suspected recurrence and 48 scans in patients who were clinically disease free. Thirty-seven PET scans were validated by histology and 66 studies by a median follow-up of 22 months in disease-free patients or 12 months in patients with recurrent disease. Three scans were validated by concordant positive findings of tumor marker CA125, computed tomography, and FDG PET.
FDG PET correctly identified recurrent disease in 73/88 cases. PET ruled out recurrent disease in 15/18 cases. The sensitivity and specificity for PET were 83 and 83%, respectively. In patients with suspected disease, sensitivity was 94% compared to 65% in patients judged clinically disease free. The sensitivity of PET was 96% if suspicion of recurrence was based on a rise of CA125 alone. PET preceded the conventional diagnosis by a median of 6 months in patients judged clinically free of disease. The median relapse-free interval after a negative PET scan was 20 months.
FDG PET provides the chance to detect recurrent ovarian cancer at an earlier stage during follow-up. Patients with a negative PET scan have a longer relapse-free interval than patients with a positive PET scan.
Gynecologic Oncology 12/2001; 83(2):310-5. · 3.89 Impact Factor
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ABSTRACT: Sertoli-Leydig cell tumors (SLCTs) represent a rare group of sex-cord stromal tumors of the ovary of unknown pathogenesis. We report a SLCT of intermediate differentiation with peritoneal recurrence and lymph node metastasis 12 months after removal, including cytogenetic analysis by comparative genomic hybridization and fluorescence in situ hybridization, which showed trisomy 8 as sole unbalanced karyotypic aberration. Our results provide evidence that a simple numeric chromosomal abnormality in SLCT may be associated with a malignant phenotype and suggest that the molecular pathogenesis of SLCT may be different from ovarian granulosa-stromal cell tumors.
Human Pathlogy 06/2001; 32(5):559-62. · 2.88 Impact Factor
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ABSTRACT: To test the value of DNA image cytometry in the differential diagnosis of hyperplastic endometrial lesions and endometrial carcinoma on a series of 153 cases of simple hyperplasia (n = 71), complex hyperplasia (n = 28), complex atypical hyperplasia (n = 11) and endometrial adenocarcinoma (n = 43).
Monolayer smears were prepared from three 50-micron-thick sections by a cell separation technique and were stained according to Feulgen. The DNA content of 250 epithelial cells, chosen randomly, was determined using a TV image analysis system (CM-1, Hund, Wetzlar, Germany). The DNA content of 30 lymphocytes served as an internal standard for the normal diploid value in every case. Different DNA cytometric parameters and the mean nuclear area were calculated.
Cases of adenocarcinoma and complex atypical hyperplasia (n = 54) were defined as clinically "positive" as these patients are normally treated by hysterectomy. The remaining cases of simple and complex hyperplasia (n = 99) were interpreted as clinically "negative" as conservative therapy is usually preferred. Requesting a specificity of > 90%, high sensitivity rates were calculated for ploidy imbalance (94%), mean ploidy (91%), diploid deviation quotient (91%), DNA stemline ploidy (87%) and 2c deviation index (85%), based on suitable thresholds. Entropy (76%), 5c exceeding events (63%), mean nuclear area (48%) and 9c exceeding events (6%) revealed lower sensitivity values. 5c Exceeding events (P = .0117) and mean nuclear area (P = .0392) were helpful in differentiating between atypical hyperplasia and endometrial carcinoma as the data distribution was significantly different with the U test.
Our results indicate that DNA single cell cytometry is a highly relevant tool in the differential diagnosis of endometrial lesions and could be used as a complementary diagnostic method, especially in histomorphologically difficult cases.
Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology 05/2001; 23(2):123-8. · 0.41 Impact Factor
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ABSTRACT: Infiltrating ductal (DC) and lobular carcinoma (LC) of the breast represent the most frequently observed varieties of invasive breast cancer, characterized by differences in their histological and clinical properties. Although comparative genomic hybridization (CGH) of invasive breast carcinomas has revealed a complex and consistent pattern of DNA copy number changes, the data with regard to type specific aberrations are limited. A comprehensive study was therefore performed on 19 LCs and 29 DCs to ascertain type-specific differences of unbalanced DNA copy number changes by CGH. Statistical analysis revealed significantly higher frequencies for underrepresentation of chromosomes 16q (p<0.01), 22 (p<0.05), and 17q (p<0.05), and a lower frequency for overrepresentation of chromosome 8q (p<0.01) in LC. Similar frequencies of non-random chromosomal changes in LC and DC were obtained for gain of 1q (74%/59%) and loss of 19p (53%/52%), parts of 1p (42%/41%) and 11q (21%/24%). Less frequently, gains mainly involving parts of chromosomes 20q, 20p, 3q, and 5p and partial losses of chromosomes 17p and 13 were observed in both groups of tumours. Minimal regions of overlapping amplifications were mapped to 17q23 exclusively in DC (17%) and 11q13-q14 in both DC and LC (21% and 11%, respectively). High occurrences of DNA copy number decreases were detected at the distal part of chromosomes 1p, 19 and 22, but further analysis is required to confirm these imbalances. It is suggested that the observed differences are involved in the development of type-specific properties of DC and LC.
The Journal of Pathology 01/2001; 193(1):40-7. · 6.32 Impact Factor
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ABSTRACT: We evaluated the role of clinical non-overt stage III diabetic nephropathy concerning the development of more frequent hypertensive complications during pregnancies of women requiring insulin.
122 unselected pregnant women treated with insulin were enrolled in the study, of whom 56 were type-1 diabetic patients and 66 patients had gestational diabetes. In 24-h urine samples, excretion rates of albumin (UAE) and beta(2)-microglobulin were determined by nephelometric analysis and a radioimmunoassay, respectively. These parameters were also measured in the serum as well as HbA(1c), fructosamine and daily blood glucose profiles.
Sixteen (15.7%) women had an elevated UAE (>30 mg/24 h), of whom three had macroalbuminuria (UAE>300 mg/24 h). Thirteen (12.7%) insulin-treated women showed microalbuminuria during pregnancy, eight with type-1 diabetes and five with gestational diabetes requiring insulin. In the entire group hypertension was observed in seven (6.9%) women of whom six had microalbuminuria. The sensitivity and specificity were 85.7% and 92.6%, respectively. The positive predictive value reached 46.2%, whereas the negative predictive value was 98.9%.
Measurement of UAE in diabetic pregnancies seems to be an useful additional parameter for risk evaluation of hypertensive disorders.
European Journal of Obstetrics & Gynecology and Reproductive Biology 08/2000; 91(2):155-8. · 1.97 Impact Factor
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ABSTRACT: It was shown in experimental and clinical investigations, that the biological behavior of malignant tumors is reflected by their proliferative activity. PCNA and Ki-67-Antigen are two nuclear antigens and considered to represent important markers of proliferation. We investigated their proliferation index in primary ovarian carcinomas and correlated the results with tumor stage, grading, histological type and survival.
The expression of PCNA and Ki-67-Antigen was immunohistochemically evaluated using the monoclonal antibodies MIB-1 and PC 10 on formalin-fixed, paraffin-embedded tissue of 49 patients. Statistical data were calculated by means of Fisher's Exact Test and Pearson's Chi 2 Test, survival was estimated by Kaplan Meier Curves.
PCNA-expression was shown in all ovarian carcinomas and Ki-67-Antigen-expression was detected with one exception (98%) in all tumors, too. No correlation could be found between Ki-67-Antigen-expression and the prognostic factors mentioned above, whereas a high PCNA-expression was significantly correlated with the tumor grading (G3), (p < 0.05). Patients with ovarian carcinomas with high PCNA proliferation index showed the tendency of a shorter overall survival.
Ki-67-Antigen and PCNA-expression could be detected in almost all primary ovarian carcinomas. PCNA compared to Ki-67-Antigen is considered to be more useful for the determination of the proliferative activity of ovarian carcinomas, although there was shown just a tendency of overall survival dependent on PCNA-expression, and there was a significant correlation only between PCNA-proliferation index and tumor grading.
Zentralblatt für Gynäkologie 01/2000; 122(7):361-7.
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ABSTRACT: We report on a patient with an eight-year history on maintenance hemodialysis treatment without residual renal function in whom pregnancy was successfully managed through to the 29th week. During this time, under carefully modified dialysis treatment, the nephrologic course, as well as materno-fetal flow relationships were unremarkable. Fetal development was appropriate for gestational age. However, pregnancy was complicated by polyhydramnios, which necessitated i.v. tocolysis. In the 28 + 6th week of gestation, cesarean section was performed because of an antibiotic-resistant fever of unclear origin which ceased within two days of delivery. Although the postnatal course of the adequately developed baby was complicated by the respiratory distress syndrome, normal development continued. We emphasize that the intensive interdisciplinary cooperation of nephrologists and obstetricians is imperative for the successful management of pregnancy under these conditions. In these pregnancies, the main fetal problems consist of premature labor because of polyhydramnios, preterm delivery, intrauterine growth retardation and stillbirth. The mother is threatened by the development of superimposed pre-eclampsia, left ventricular failure because of volume overload and progressive anemia. In order to maintain a well-balanced homeostasis, intensification of dialysis therapy by an increase in frequency and duration is the most important therapeutic approach. Accurate fetal monitoring including frequent examination of the feto-maternal circulation by Doppler sonography as well as attentive surveillance of the mother is required to recognize the above mentioned complications.
Renal Failure 10/1999; 21(5):533-9. · 0.82 Impact Factor
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ABSTRACT: The purpose of the present study was to evaluate the clinical significance of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) for endothelial cell activation in pre-eclampsia. Therefore, we determined and compared the correlations between these cytokines and circulating adhesion molecules in the sera of pre-eclamptic pregnant women, normotensive pregnant women and nonpregnant women.
The soluble adhesion molecules VCAM-1, ICAM-1, E-selectin, and P-selectin were determined in the serum of 38 pre-eclamptic pregnant women and 40 normotensive pregnant and nonpregnant controls using ELISA-techniques. We correlated these serum concentrations with the serum levels of TNF-alpha and IL-1beta, respectively, also determined by ELISA.
Elevated serum levels of VCAM-1 and E-selectin could be detected in pre-eclamptic patients, with and without HELLP-syndrome. In contrast, no increased serum concentration of ICAM-1, P-selectin, TNF-alpha and IL-1beta were found in these patients. While significant correlation between VCAM-1 and E-selectin could be determined (r=0.604; p<0.001) no unambiguous correlations, however, were found between TNF-alpha or between IL-1beta and the examined adhesion molecules or the selectins.
In contrast to in vitro investigations on cultured umbilical vein endothelium, our experimental results indicate that the cytokines TNF-alpha and IL-1beta can not explain endothelial cell activation, and that their measurement in serum is not useful for the detection of pre-eclampsia.
European Journal of Obstetrics & Gynecology and Reproductive Biology 09/1999; 86(1):35-41. · 1.97 Impact Factor
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ABSTRACT: We evaluated the clinical significance of 18F-FDG PET to detect malignant ovarian neoplasms and tumor spread. 40 patients (median age: 57.5 years) underwent laparotomy because of clinical suspicion of malignant ovarian tumors or recurrent disease. The results of the preoperatively performed PET were correlated with the postoperative histologic diagnosis and the intraoperatively assessed tumor spread. In 10 of 40 patients benign tumors were found, among which a tubo-ovarian abscess was the only one diagnosed as false positive. 4/30 malignant neoplasms did not originate from the coelomic epithelium, but all were correctly recognized as malignant tumors by PET, as was recurrent ovarian cancer in 12 patients. Out of 14 primary ovarian carcinomas, 2 borderline tumors and 1 well-differentiated adenocarcinoma FIGO stage I were not correctly identified. Considering the tumor type, sensitivity, and specificity were 90%, calculating for the positive and negative predictive value 96% and 75%, respectively, and 90% for the diagnostic accuracy. Those statistical parameters were slightly lower for PET detection of lymph node metastasis and peritoneal carcinomatosis. Although its diagnostic accuracy may vary depending on the clinical application, 18F-FDG PET is basically a suitable method for detecting ovarian malignancies, particularly in patients with relapsed ovarian carcinoma.
International Journal of Gynecological Cancer 04/1999; 9(2):117-122. · 1.65 Impact Factor
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ABSTRACT: Human papillomavirus (HPV) infection is common in cervical intraepithelial neoplasia (CIN). This study investigates HPV detection and typing assay based on polymerase chain reaction amplification of L1 open reading frame with general primers GP5/GP6, followed by enzyme-linked immunosorbent assay detection with type-specific DNA probes. To determine the sensitivity of this assay, formalin-fixed CaSki cells were used as reference cell lines. Fifty copies of viral DNA diluted in DNA from 100,000 noninfected cells could be detected. This assay was also investigated for HPV detection and typing of 67 cervical specimens diagnosed with with CIN III or carcinoma in situ (CIS) and their adjacent squamous epithelium. The CIN III lesions were infected in approximately 80% of the samples, 81% in the neighboring CIN II, and 68% in CIN I. The HPV infection was even detectable in 54% of nondysplastic epithelium located near a CIN III lesion.
Diagnostic Molecular Pathology 04/1999; 8(1):32-8. · 2.26 Impact Factor
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ABSTRACT: We report on Doppler sonographic findings of a dialysis patient with renal anemia during otherwise uncomplicated pregnancy. Uteroplacental and fetoplacental flow relationships before, as well as after the dialysis treatments during the course of the pregnancy were in the normal range. The favorable flow condition in the utero- and fetoplacental circulation was associated with a low hematocrit. This in accordance with previous reports indicates a more favorable maternal and fetal outcome in association with a low hematocrit/hemoglobin concentration.
Clinical hemorheology and microcirculation 10/1998; 19(1):33-7. · 3.40 Impact Factor
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ABSTRACT: The prognostic significance of immunohistochemical markers for cell proliferation [MIB-1, proliferating cell nuclear antigen (PCNA)] and hormone receptor analysis [oestrogen receptor (ER), progesterone receptor (PR)] was tested by means of immunohistometry in a series of 103 breast cancer patients in comparison with the lymph node status N, the tumour size T, histomorphological grading, and the biochemical ER and PR status. Immunohistochemical reactions were performed on 2 microns sections from paraffin-embedded tissue, using an indirect peroxidase method. The proportion of immunostained tumour cell nuclei was determined using a TV-image analysis system. Measurements were performed using a 20 x objective on 40 viewing fields (1.94 mm2, MIB-1 and PCNA) or 20 viewing fields (0.97 mm2, ER and PR). The mean immunopositivity of all viewing fields and the value of the most immunopositive viewing field (MIB-1max, PCNAmax, PRmax, ERmax) were calculated. The mean values and the maximal values were highly correlated (r = 0.903, P < 0.001). After 1:2:1 quantilization, 84.2 per cent of the 412 single measurements revealed mean and maximal values in the same category (P < 0.0001). For each of the four immunohistochemical markers, the prognostic significance of the maximal values was higher than that of the mean values. The highest prognostic significance was found for MIC-1max (P = 0.0002), followed by PRmax (P = 0.0046), ERmax (P = 0.0154), and PCNAmax (P = 0.0161). From the results of a Cox model, a 'prognostic index (PI)' was developed, ranging from -1 to 8: PI = 2 x N + T + MIB-1max-PRmax. The four groups of patients with PI values of < 2, 2-3, 4-5, and > 5 revealed significantly different 7.5-year survival probabilities (P < 0.0001). The simplicity of the PI makes it a clinically useful, routinely applicable, and understandable parameter in the surgical pathology of breast carcinoma.
The Journal of Pathology 05/1998; 185(1):25-31. · 6.32 Impact Factor
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ABSTRACT: Ovarian cancer is the leading cause of death from gynaecological malignancies in western countries, it is diagnosed at an advanced stage in approximately 75% of patients. The current standard treatment for ovarian cancer consists of maximum cytoreductive surgery to reduce tumor residuum to a minimum, followed by platin-based chemotherapy. If an unsuspected ovarian cancer is detected at diagnostic laparoscopy, staging and debulking by laparotomy should be undertaken without delay. For apparently early stages (I or II), appropriate surgical staging is extremely important and will result in the upstaging of about one-third of patients (usually to Stage III). Several retrospective clinical trials show that successful cytoreduction and systemic lymphonodectomy result in an improved survival, but prospective randomized studies have not been performed to evaluate this benefit. Patients who cannot initially be cytoreduced to an optimal stage should be considered candidates for interval cytoreduction after chemotherapy. Repeated surgical debulking in relapsed patients will probably only benefit a small subset of selected patients (e.g. disease-free interval > 2 years). Surgery may also be important for palliation, such as for the treatment of bowel obstruction to improve the patients quality of life. The question still remains whether the observed improved survival rates for patients with ovarian cancer are an effect of primary cytoreductive surgery or tumor biology.
Zentralblatt für Gynäkologie 02/1998; 120(1):3-16.
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ABSTRACT: The characteristic features of the Cantrell-sequence--anterior thoraco-abdominal wall defect with ectopia cordis and diaphragm, sternum, pericardium, and heart defects--have been observed in animals following maternal administration of beta-aminopropionitrile, a toxic amino-acid derivative. We report on an unusual case of the Cantrell-sequence in a premature infant with associated dysmelia, aplasia of the right kidney, cerebellar hypoplasia and circumscribed aplasia of the cutis, which has not been reported previously. Maternal history suggested an occupational exposure to aminopropionitriles prior to pregnancy. Prenatal ultrasound, differential diagnosis, perinatal management, and the teratogenic role of aminopropionitriles in this rare genetic disorder are discussed.
American Journal of Perinatology 11/1997; 14(9):567-71. · 1.32 Impact Factor
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ABSTRACT: Of the present study was to evaluate 18FDG PET as a diagnostic tool in primary and recurrent ovarian cancer.
PET of the abdomen and the pelvis was performed in 26 patients suspected for primary (n = 17) or recurrent (n = 9) ovarian cancer with an ECAT 953/15 scanner 45 min after intravenous administration of 245 MBq 18F-FDG (mean). PET findings were validated by surgery, histology and/or cytology.
Ovarian malignancies or recurrent ovarian cancer were demonstrated by PET in 16 out of 19 cases. Malignancy was excluded in six out of seven cases. False negative findings were obtained in two cases of low malignant potential tumors (LMP) and in one case of low grade serous/mucinous ovarian cystadenocarcinoma. PET yielded one false positive result in a case of salpingoophoritis. Quantitative analysis revealed a mean SUV of 6.8 +/- 2.3 in primary ovarian carcinoma vs. 2.6 +/- 1.2 in benign masses (p < 0.05).
These preliminary data show 18FDG PET to be useful in diagnosis of recurrent ovarian cancer. PET is of limited use in differentiating LMP from benign tumors and ovarian cancer from inflammatory processes. Concerning this differentiation, quantitative analysis does not improve diagnostic accuracy.
Nuklearmedizin 10/1997; 36(7):228-33. · 1.28 Impact Factor
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ABSTRACT: Uterine metastases of malignant tumours are rare. Among extragenital malignancies breast cancers of the lobular type most likely spread out to this site. The respective diagnosis is rendered more difficult by the late onset of clinical symptoms that may imitate the picture of primary uterine cancer. We report on a patient with advanced invasive lobular breast cancer (ILC) where this form of metastazation was detected after conization for PAP IVa. Especially in patients with advanced lobular breast cancer and suspicious symptoms (such as pathologic PAP-Smear, conspicuous colposcopic finding, vaginal bleeding, growth-progressive uterus and hyperplastic endometrium) the possibility of uterine metastases should be included in preoperative planning.
Zentralblatt für Gynäkologie 02/1997; 119(10):500-2.
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Journal of Obstetrics and Gynaecology 01/1997; 17(1):61. · 0.54 Impact Factor
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ABSTRACT: Conventional transvaginal ultrasound-and transvaginal colour Doppler flow were used to assess morphology and circulation of pelvic masses.
One hundred and nine adnexal masses in 101 women were examined between January 1993 and September 1994. Morphology was classified after a score published by Sassone et al. in 1991. Doppler waveforms using the lowest resistance index (RI), the pulsatility index (PI) and peak flow velocity were used for analysis. Ninety five patients underwent laparotomy. Following histopathological evaluation best cut-off values, sensitivity and specificity were calculated. Score results were compared with Doppler results and a combination of both methods.
A combination of Doppler sonography and conventional transvaginal sonography led to a sensitivity of 74.0% and a specificity of 73.7%. Eight out of 15 malignant masses were classified as stage I. An analysis of the false positive diagnoses showed that important information can be gained when Doppler sonography is performed. In particular, on solid appearing adnexal masses, Doppler sonography leads to a high accuracy (84.6%).
Colour Doppler sonography is not applicable in routine clinical practice, but can give important additional information in specific cases. For solid appearing masses and in early ovarian malignancy, Doppler sonography facilitates the preoperative discrimination between benign and malignant processes.
European Journal of Obstetrics & Gynecology and Reproductive Biology 02/1996; 64(1):79-85. · 1.97 Impact Factor
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ABSTRACT: A 24-year-old patient with dysgerminoma of the right ovary and hypoplastic left ovary was screened for chromosomal aberration. Triple-X syndrome was found in the oral epithelium and lymphocyte culture, while chromosomal in situ hybridization of the tumor itself showed a normal XX karyotype. Although trisomy X and dysgerminoma are coincidental findings in our case report, women with malignant germ cell tumors and abnormal genitalia should be checked for chromosomal aberrations to exclude anomalies carrying a Y chromosome.
International Journal of Gynecology & Obstetrics 08/1995; 50(1):51-3. · 2.05 Impact Factor
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ABSTRACT: Postpartal screening of undetected gestational diabetes has proven to be difficult. Rapid decrease in diabetogenic hormones and normalisation of the former delayed insulin-response make it difficult to detect disturbed glucose tolerance in the puerperium. Therefore, glycolysated serum proteins offer the opportunity for retrospective diagnosis. They allow an evaluation of the patient's carbohydrate metabolism, retrospectively over several weeks. In this context, we were most interested in the significance of fructosamine. In a prospective study covering 12 months, 123 patients with several risk factors for gestational diabetes underwent a 100 g glucose tolerance test in the puerperium. Furthermore, we measured fructosamine and glycolysated hemoglobin. A carbohydrate intolerance could be detected by the oral glucose tolerance test in 22.7%. In 12.2% of the cases, glycolysated hemoglobin was found to be higher than 5.5%. Fructosamine levels were normal for all patients, with a mean value of 1.84 mmol/l. Even though fructosamine concentration was significantly higher (p < 0.05) in patients with a pathologic glucose tolerance, our study showed the oral glucose tolerance test to be better to detect unknown gestational diabetes than measurement of serum fructosamine.
Zentralblatt für Gynäkologie 01/1995; 117(5):269-73.
