Biphasic sarcomatoid carcinoma or carcinosarcoma of the breast: prognosis and therapy.

Biphasic sarcomatoid carcinoma of the breast represents only 0.2% of all breast cancer. Due to its rarity and repetitive reclassifications little is known about optimal treatment modalities. These tumours form a diagnostic and therapeutic challenge. The present report describes our experience with a case of biphasic sarcomatoid carcinoma of the breast and a review of the relevant literature is discussed.

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.

Detection of estrogen DNA-adducts in human breast tumor tissue and healthy tissue by combined nano LC-nano ES tandem mass spectrometry.

For the first time estrogen DNA-adducts were identified in DNA human breast tumor tissue using nano-LC coupled to nano-Electrospray Tandem Mass Spectrometry. Normal breast tissue was analyzed analogously. The data obtained in the five breast tumor and five adjacent normal tissue samples were compared qualitatively, but no straightforward difference was observed. Prior to LC-MS analysis the DNA was enzymatically hydrolyzed to a nucleoside pool. The DNA-hydrolysates were directly injected onto a column switching system developed for on-line sample clean-up and subsequent analysis of the DNA-adducts. In four patients using Premarin, DNA-adducts of 4-hydroxy-equilenin (4OHEN) were detected. All except three samples contained DNA-adducts from 4-hydroxy-estradiol or 4-hydroxy-estrone. Also DNA isolated from eight alcohol fixed and paraffin embedded breast tumor tissue showed the presence of different estrogen DNA-adducts. Worthwhile mentioning is the presence of adducts responding to m/z 570 > m/z 454 transition. This is a well-known SRM-transition indicative for the presence of the 2'-deoxyguanosine (dGuo) adduct of Benzo[a]pyrene.

Invasive papillary carcinoma of the male breast.

Intracystic papillary carcinoma of the male breast is a very rare disease with only a few cases reported in the literature. A case is described and the additional value of MRI is discussed. To our knowledge, this is the first report regarding the MRI findings of an intracystic papillary carcinoma of the male breast.

Prevalence of human papillomavirus in elderly women with cervical cancer.

To investigate the relation between the prevalence of human papillomavirus (HPV) and age in cervical cancer patients, material from 93 patients with Ia-IIb cervical carcinoma was analyzed for the presence of HPV by both type-specific and general primer polymerase chain reaction. Patients were divided into 2 groups: 64 years or younger, and 65 years and older. There was no statistically significant difference in either the prevalence of HPV DNA or distribution of genotypes amongst the 2 groups. Therefore, HPV detection can be equally well used in the management and follow-up of elderly cervical cancer patients.

Human papillomavirus infection in the female population of Antwerp, Belgium: prevalence in healthy women, women with premalignant lesions and cervical cancer.

Worldwide there is a strong relation between the presence of human papillomavirus (HPV) and the development of cervical cancer. This study investigated the prevalence and genotype of HPV in women with normal smears, women with premalignant lesions and women with cervical cancer in Antwerp, Belgium. Type-specific polymerase chain reaction (PCR) for HPV types 16 and 18 and general primer PCR (GP5+/6+) was performed on DNA extracted from paraffin-embedded tissue from women with lesions or fresh material from controls. HPV was detected in 11% of controls, 61% of women with atypia, 77% of women with CIN lesions and 88% of women with cervical carcinoma (chi2 trend, 273, p<0.001). The odds ratio for high-risk HPV types was 9.3 for atypia (95%CI. 4.3-19.8), 33.6 for CIN lesions (95%CI, 19.3-58.6) and 78.8 for cervical cancer (95%CI, 39.2-158.3). In total, 19 different HPV genotypes were detected, including five low risk HPV types. Seven of the 14 high-risk HPV types were detected in cervical cancer patients. Based on our study it is suggested that a prophylactic vaccine based on a cocktail of a limited number of high-risk HPV types should be considered in order to protect most women from developing cervical cancer.

Reduction of visible bone metastases by clodronate therapy in breast cancer.

The current report describes a 57-year-old patient with multiple bone metastases 14 years after her initial treatment for breast cancer. The only therapy the patient received for her osteolytic lesions was oral clodronate (800 mg/daily), as she refused any other kind of treatment. On bone scintigraphy the number of visible bone metastases diminished slowly and after two years only a few minor lesions could be seen. Together with this report the value of oral clodronate as anti-osteolytic therapy in breast cancer patients is discussed.

The importance of biological factors (bcl-2, bax, p53, PCNA, MI, HPV and angiogenesis) in invasive cervical cancer.

OBJECTIVE: The present study was designed to analyse the relationship between apoptosis related proteins (bcl-2 and bax), tumour suppressor protein p53, proliferation markers (PCNA and mitotic index), human papillomavirus (HPV) and angiogenesis in cervical cancer and their impact on clinical outcome. STUDY DESIGN: Tumours from 111 patients were assessed by immunohistochemistry for the expression of bcl-2, bax, p53 and PCNA, by PCR for the presence of HPV-DNA, for the quantification of the mitotic index and the microvessel density (CD 31). The results were correlated with various histopathologic characteristics and survival. RESULTS: The multiple Cox's regression analysis for overall survival of all prognostic variables gave as best model: bcl-2 (P<0.001), lymphovascular permeation (P=0.004), mitotic index (P=0.019), tumour grade (P=0.048) and FIGO stage (P=0.070). Subanalysis was performed for the patients where the lymph node status was known (n=79). Adding the lymph node status gave as best model for overall survival bcl-2 (P=0.001), lymphovascular permeation (P=0.003) and mitotic index (P=0.044). However, they hardly influenced the association. CONCLUSION: In the apoptotic pathway of cervical cancer, bcl-2 is one of most important proteins. It can probably not only mediate cell death but also regulate cell growth. A better understanding of their relations will probably provide the basis for more rational cancer therapies in the future.

Observations of an idiopathic granulomatous mastitis.

Idiopathic granulomatous mastitis is a very rare benign breast disease, which mimics breast cancer both clinically and mammographically. Most cases have an unknown aetiology, however, we found an alpha-1-antitrypsin deficiency. A literature review is presented and the controversies in diagnosis and management are discussed.

Intrauterine versus postnatal transport of the preterm infant: a short-distance experience.

AIM: The purpose of this study was to compare neonatal outcome (mortality, respiratory distress syndrome, intraventricular hemorrhage, necrotising enterocolitis, persisting ductus arteriosus, and septicaemia) after intrauterine transport versus neonatal transport in an area where short-distance transport is the rule. METHODS: The study was retrospective in nature. The files of all neonates delivered between 24 and 34 weeks from 1994 to 1998 and transported intrauterine or postnatally to the Antwerp University Hospital were reviewed. Cases of intrauterine fetal death and mothers discharged before delivery were excluded, as were infants with lethal congenital anomalies. RESULTS: A total of 328 deliveries after intrauterine transport, resulting in 416 neonates and 187 neonates transported postnatally were included. The maximum distance patients had to be transported was 40 km. Placental abruption was more frequent in the mothers of the neonatal transport group (13 vs. 5%, P=0.001). Corticosteroids were administered significantly less in the neonatal transport group (67 vs. 13%, P<0.0001). Preterm rupture of the membranes (36 vs. 20%, P<0.0001), preterm labour (73 vs. 36%, P<0.0001), and pre-eclampsia (10 vs. 7%, P<0.0001) were more frequent in the intrauterine transport group and this group had a lower mean birthweight and gestational age. There was no significant difference for overall neonatal mortality, respiratory distress syndrome, intraventricular hemorrhage, necrotising enterocolitis, persisting ductus arteriosus or septicaemia.

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.

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.

[Primary malignant melanoma of the female urethra]. / Primäres malignes Melanom der weiblichen 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.

Trocar implantation metastasis after laparoscopy in patients with advanced ovarian cancer: can the risk be reduced?

OBJECTIVE: The purpose of this study was to determine risk factors for trocar implantation metastasis after diagnostic laparoscopy in patients with primary or recurrent advanced ovarian cancer. STUDY DESIGN: Eighty-three women with primary advanced ovarian cancer and 21 women with recurrent ovarian cancer undergoing a laparoscopy for a tissue diagnosis and for assessment of operability were included in the study. The occurrence of implantation metastasis at the trocar incision scars was analyzed according to clinicopathologic characteristics. RESULTS: A recurrence developed at the trocar site in 7 (58%) of 12 patients undergoing a laparoscopy in which only the skin was closed at the end of the procedure and in 2 (2%) of 92 patients undergoing a laparoscopy with closure of all layers (odds ratio, 63; 95% confidence interval, 10.3-385; P <.001). The International Federation of Gynecology and Obstetrics stage at initial presentation, tumor histologic type, tumor differentiation, maximal tumor diameter at the time of diagnosis, estimated weight of the metastatic tumor, residual tumor after cytoreductive surgery, surgical characteristics, and type of chemotherapy were well balanced among both groups. Patients with implantation metastasis had significantly more ascites (median, 700 mL vs 300 mL; P =.032) and a longer interval between the start of platinum-based chemotherapy or cytoreductive surgery (median, 6 days vs 17 days; P <.01) compared with patients without abdominal wall recurrence. A palpable abdominal wall metastasis developed in none of the patients undergoing a laparoscopy with closure of all layers of the abdomen followed by cytoreductive surgery or chemotherapy within 1 week after the laparoscopy. Kaplan-Meier survival analysis showed that patients with abdominal wall implantation metastasis had a survival rate similar to that of the other patients. CONCLUSIONS: Laparoscopy with careful closure of the peritoneum, rectus sheath, and skin followed by chemotherapy or cytoreductive surgery with excision of the trocar trajectories within 1 week is safe in patients with disseminated ovarian cancer.

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.

Second trimester maternal dimeric inhibin-A in the multiple-marker screening test for Down's syndrome.

The aim of this study was to evaluate the additional value of dimeric inhibin-A serum concentration in second trimester multiple-marker screening tests for pregnancies affected by Down's syndrome. We anticipated that second trimester maternal serum dimeric inhibin-A concentrations would be altered in pregnancies complicated by fetal Down's syndrome and that dimeric inhibin-A would perform better than one of the three substances analysed in the multiple-marker screening test currently in use. A total of 1156 serum samples were screened for dimeric inhibin-A in parallel with the routine classic triple test screening programme performed on a random obstetric population. Classic triple test performance was compared with detection rates obtained after substitution of unconjugated oestriol by inhibin-A and with the performance of inhibin-A and alpha-fetoprotein alone. Absolute dimeric inhibin-A maternal serum concentrations of Down's syndrome pregnancies were indeed significantly higher than those of normal pregnancies in our screened population. The performance of dimeric inhibin-A in combination with the multiple-marker screening test, however, is limited because of its strong correlation with intact human chorionic gonadotrophin.

Dimeric inhibin serum values as markers of ovarian activity in pill-free intervals.

Levels of inhibin A and B as well as other hormones in serum samples obtained during the pill-free interval in women taking combined oral contraceptives (OC) were measured to asses the extent of ovarian activity during that period. Type of pill and day of pill-free interval were recorded during routine gynecologic check-ups, if patients were in the pill-free period and had taken their pills regularly in the previous cycle. In addition to inhibin A and B, serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and progesterone were also quantified. Inhibin B levels rise significantly in parallel with rising levels of FSH, LH, and E2. Progesterone levels were completely suppressed and inhibin A levels rose slightly but insignificantly. Inhibins are sensitive biochemical markers of ovarian activity in pill-free intervals.

PIP: Serum values of dimeric inhibin A and B were measured to assess the restoration of pituitary and ovarian activity during the pill-free interval in women taking combined oral contraceptives. 175 healthy women 18-35 years of age from five areas in Belgium were enrolled and monitored during routine gynecologic examinations. During the 7 day pill-free interval, inhibin B levels rose significantly in parallel with rising levels of follicle-stimulating hormone, luteinizing hormone, and estradiol. Progesterone levels were completely suppressed. Inhibin A levels rose slightly but insignificantly, reflecting an absence of development of preovulatory follicles. These findings indicate that inhibins are sensitive biochemical markers of ovarian activity in pill-free intervals. Inhibin B appears to be predominantly a product of the cohort of developing primary and subsequent early antral follicles, while inhibin A secretion is more indicative of dominant follicular and corpus luteum function.

The addition of indomethacin to betamimetics for tocolysis: any benefit for the neonate?

OBJECTIVE: To study the influence on the neonate of indomethacin administered to the mother as an additional tocolytic. STUDY DESIGN: The neonatal outcome in 76 closely matched low birth weight infants was compared retrospectively: those whose mothers received indomethacin together with betamimetics formed the study group, those whose mothers received only betamimetics formed the control group. RESULTS: There was an increased incidence of respiratory distress syndrome (RDS) in the study group (97% versus 45%; P<0.001), an increased need for surfactant use (68% versus 26%; P<0.001) and increased ventilatory support, and an increased incidence of bronchopulmonary dysplasia (BPD) (47% versus 24%; P=0.03). Gestation could not be prolonged significantly by the addition of indomethacin. CONCLUSION: Indomethacin as an additional tocolytic agent was associated with an increased incidence of RDS, surfactant use and BPD but did not significantly prolong gestation.

Spontaneous rupture of the uterine artery in pregnancy.

A case of spontaneous rupture of the uterine artery in the third trimester of pregnancy is described. Review of the literature reveals only three similar cases. Clinical signs are sudden abdominal pain with hemodynamic collapse and a decrease in the level of hemoglobin. Treatment consists in performing a laparotomy with suturing of the ruptured artery.