Changes in vascular endothelial growth factor (VEGF) after chemoendocrine therapy in breast cancer.

PURPOSE: Angiogenesis has been proposed as a possible target for anticancer treatment, either by inhibition of the production of angiogenic factors or by inhibition of endothelial cell proliferation. The impact of preoperative chemoendocrine therapy is unknown in the regulation of angiogenic factors, but recent reports suggest that anticancer drugs have antiangiogenic activity. METHODS: The expression of two angiogenic factors VEGF and Angiopoetin-1 were quantified at different concentrations of doxorubicin, docetaxel, tamoxifen, exemestane and letrozol on MCF-7 and T47D cells. RESULTS: Low-drug concentrations led to increased VEGF-A gene transcription whereas high (10-fold increased) drug concentrations suppressed gene expression. A similar cell reaction was observed for VEGF protein with a smaller variety in the extent of modulation. Incubation of MCF-7 cells to different drugs showed a similar dose-dependent modulation of Angiopoietin-1 gene expression with enhancement at low-drug concentrations. CONCLUSION: Treatment of breast cancer cells following a preoperative protocol showed a dose-dependent expression of VEGF and Angiopoetin-1. Only high-drug concentrations were followed by a decreased secretion of both factors whereas low concentrations induced up-regulation of VEGF and Angiopoietin 1.

Large-core needle biopsy for diagnosis and treatment of breast lesions.

PURPOSE: Large-core needle biopsy (LCNB) has become a more widely used technique in the evaluation of breast lesions. This study was undertaken to access the accuracy of percutaneous LCNB on breast lesions and the impact on further proceeding. METHODS: A retrospective review of imaging-guided LCNB of 159 breast lesions was done. 143 LCNB were taken with ultrasound guided automated spring gun biopsy and 16 stereotactic-guided with vacuum-assisted biopsy device. Histology and morphobiological parameters were compared with subsequent material from surgery. RESULTS: In 113 core biopsies (71%), an infiltrating breast cancer was diagnosed, 5 biopsies (3%) yielded in-situ/atypical lesions and a benign lesion was shown in 38 cases (24%). In 3 cases, insufficient/necrotic material was obtained. 108 patients underwent subsequent surgery. In 100/108 cases (93%), histology on LCNB and surgery was identical. LCNB was false negative in 5 core biopsies (5%). Immunhistochemical stains of hormone receptors, bcl-2, c-erbB-2, p53 and MIB-1 was comparable on LCNB and on surgical material. Based on the results of LCNB, 17/113 patients (15%) with infiltrating carcinoma were primarily treated with hormones or with neoadjuvant therapy. 32/38 patients (84%) with benign lesions were followed up by imaging control. CONCLUSIONS: In patients with benign lesions on imaging, open biopsies can be avoided by LCNB. In patients with biopsy proven carcinoma, therapy planning is improved. The addition of morphobiological parameters allows early individual treatment.

[Clinical experience with large-core needle biopsies of the breast and evaluation of histopathology]. / Klinische Erfahrungen mit perkutanen Biopsien der Brust und deren histologische Beurteilung.

OBJECTIVE: Interventional techniques allow a microinvasive diagnostic of breast lesions. We examined the reliability of large core needle biopsies for histologic diagnosis on breast lesions. MATERIAL AND METHODS: 143 ultrasound guided automated spring gun biopsies and 16 stereotactic guided vacuum-assisted device biopsies were analyzed. Indications included confirmation of malign or benign lesions and diagnosis of suspicious lesions. RESULTS: In 113 biopsies (71%) an invasive breast carcinoma was diagnosed, in 5 biopsies (3%) in situ/atypical lesions were seen and 38 cases (24%) showed benign lesions. Based on the bioptic results, 108 patients underwent subsequent surgery. An identical histology was seen in 100/108 patients (93%), 5 biopsies were false negative (5%) and 3 specimens yielded necrotic/insufficient material. The immunohistochemical results of percutaneous biopsies and surgical specimens were comparable. 17 out of 113 patients (15%) with biopsy proven carcinoma were treated with neoadjuvant therapy. 32/38 patients with benign lesions were follow-up clinically. CONCLUSION: Ultrasound- or stereotactic guided percutaneous biopsies are methods to confirm histological diagnosis. Based on the biopsy results the, number of surgical excisions can be reduced and treatment of biopsy proven carcinoma can be improved by individual presurgical planing.

A multivariate analysis of clinical and morphological prognostic factors in squamous cell carcinoma of the vulva.

Clinical and histological data of 168 patients with squamous cell carcinoma of the vulva were analyzed with respect to survival. 151 patients underwent surgery, 12 patients were treated with primary radiation and in 5 patients no treatment was performed. Follow-up lasted from at least 2 up to 22 years' posttreatment. In univariate analysis, the following factors were highly significant: presurgery lymph node status, tumor infiltration beyond the vulva, tumor grading, histological inguinal lymph node status, pre- and postsurgery tumor stage, depth of invasion and tumor diameter. In the multivariate analysis (Cox regression), the most powerful factors were shown to be histological inguinal lymph node status, tumor diameter and tumor grading. The multivariate logistic regression analysis worked out as main prognostic factors for metastases of inguinal lymph nodes: presurgery inguinal lymph node status, tumor size, depth of invasion and tumor grading. Based on these results, tumor biology seems to be the decisive factor concerning recurrence and survival. Therefore, we suggest a more conservative treatment of vulvar carcinoma. Patients with confined carcinoma to the vulva, with a tumor diameter up to 3 cm and without clinical suspected lymph nodes, should be treated by wide excision/partial vulvectomy with ipsilateral lymphadenectomy.

Morphologic criteria for the prognosis of serous cystadenocarcinoma of the ovary.

143 cases of serous ovarian cystadenocarcinoma were studied to establish the prognostic relevance of specific macroscopic and microscopic criteria. Significant differences in the survival rate were found depending on TNM classification, age, residual tumor mass, ascites, and degree of invasion. The prognosis was significantly better for normotypical or predominantly cystic tumors as well as for those with mononuclear infiltration, little histological atypia, or limited invasion. No prognostic relevance was found, however, for cytologic criteria such as Broder's grading and rate of mitosis.

[The value of colposcopy and portio biopsy in preventive examination]. / Zum Stellenwert der Kolposkopie und der Portiobiopsie bei der Vorsorgeuntersuchung.

133 patients attending the colposcopy-laser outpatient consultations were examined simultaneously by cytology, colposcopy and punch biopsy. A cone biopsy was taken 25 patients and one patient was hysterectomised later. A comparison between cytology and histology revealed 17.1% false negative smear results. Cytology and histology showed the same result in 84.6%. The highest percentage of high-grade dysplasia was found in colposcopy with signs of punctation and/or mosaicism. A similar diagnosis was achieved in 92.3% of cases comparing punch with cone biopsy. Simultaneous use of cytology, colposcopy and punch biopsy enables reliable diagnosis and follow-up of dysplastic lesions of the cervix. Besides, one can use punch biopsy as basic histology for local destructive manoeuvres such as laser vaporisation.

Pseudolymphoma of the nipple.

Pseudolymphoma of the breast is a rare benign disorder. To avoid over-treatment or misdiagnosis of a malignancy of the breast, exact histological diagnosis is important. We report on a 69-year-old patient, who presented with symptoms of mastitis.

[Condylomata acuminata in pregnancy. Is there an indication for Cesarean section?]. / Condylomata acuminata in der Schwangerschaft. Besteht eine Sektioindikation?

Condylomata acuminata are very rare in children, although the prevalence of clinically or cytologically visible human papilloma virus infections is high. We report on a 28-year old G IV, P II with genital warts at the time of delivery, who had a baby boy without any signs of HPV-infection. The condylomata of the mother persisted, and subsequently laser vaporisation was performed one year after delivery. One year after laser therapy, a recurrent HPV-infection in the mother was detected. At this time, her two year old son had condylomata on his scrotum. The same serotypes, HPV 6 and 11, could be identified in the mother and child. With this case report, we discuss the possible ways of transmission and consequent clinical management of HPV infections in pregnancy.

Evaluation of steroid hormone receptors with respect to tumor cellularity.

The cellularity grade of 350 carcinomas of the breast was determined in retrospect, and from these results 3 corrective factors were established. After biochemically assessing the concentrations of estrogen and progesterone receptors, these were compared with tumor size, histological type and cellularity. As expected, ductal carcinomas showed higher average hormone receptor concentrations than lobular or medullary carcinomas. There was no evidence of a positive correlation between receptor concentration and cellularity grade. Many times, an initially negative receptor status in the lobular carcinomas with their relative paucity of cells was modified to a positive status. Accordingly, further possible therapeutic approaches should be discussed with respect to tumor cellularity.

[Laser therapy of the vulva, perineal area and uterine cervix]. / Lasertherapie an der Vulva, im Perianalbereich und an der Portio.

Within a period of two years 205 patients of our colposcopy-laser-outpatient department have been treated with a 40 Watt CO2-laser. 97 patients had dysplastic or condylomatous lesions of the portio, 85 ones condylomas in the vulvar, vaginal or perianal regions. 70 per cent of laser vaporisations had been done ambulatoryly. Complication rate following laser conisation was 12 per cent, following laser vaporisation 0 per cent. The rate of recurrent or persistent dysplasias was 12 per cent, of condylomas 18 per cent on an average observation time of 16 months.

Diagnosis and follow-up of atypical hyperplasia of corpus endometrium--a critical methodological investigation.

Within 5 years 181 patients were diagnosed with grade I and grade II atypical hyperplasia (AH) in the curettage material of 4193 specimens at the University Department of Gynecology and Obstetrics in Tübingen. In 62.6% of grade I and in 38.8% of grade II AH, concomitant endometrial polyps were observed, rarely cystic alterations as well. Especially with AH grade II, most polyps exhibited epithelial proliferation. Plurifocality and in situ residuals of AH were seen (grade I 38.5%, grade II 77.3%). In the same time period 345 endometrial carcinomas were found. Due to embedding techniques and the observation that only approximately 60% of the cavum uteri surface is reached via curettage, diagnostic security is quite limited. It has been published that women with AH have a higher risk of developing endometrial carcinoma. A control curettage after 6 months or a wide indication for hysterectomy is recommended after atypical endometrial hyperplasia has been demonstrated.

[Suspected abortion: morphologic aspects--value of histological examination of curettage specimen in suspected abortion and extra-uterine pregnancy]. / Abortverdacht: Morphologische Aspekte--Aussagefähigkeit der histologischen Untersuchung des Abradates bei Abort- und EUG-Verdacht.

Curettage specimens of 104 patients with clinically suspected abortion and unknown localization have been examined histologically. 50 patients with defined ectopic pregnancy, 51 patients with proved abortion and 50 patients with legal abortion had been used to compare with. In two cases syncytial cells could be proved histologically and by this an abortion could be verified. We could see decidually transformed endometrium in all cases with uncertain or certain formerly intrauterine localization of pregnancy. Opposite to this in ectopic pregnancy we could observe this only in 54 per cent. Summarizing our results in abortions as well as in ectopic pregnancies similar histologic findings could be seen.

Endometrial cancer associated with polycystic ovaries in young women.

Two women (17 and 36 years old) are presented, who complained about abnormal vaginal bleeding. The rare diagnosis of an adenocarcinoma of the corpus uteri with concomitant polycystic ovaries (Stein-Leventhal-Syndrome) was made.

[Analysis of lymph node status and lymph node morphology in cervix cancer operated by the Wertheim-Meigs-Okabayashi method]. / Analyse des Lymphknotenstatus und der Lymphknotenmorphologie bei nach Wertheim-Meigs-Okabayashi operierten Kollumkarzinomen.

We evaluated in the histologic labor, of the Department of Obstetrics and Gynaecology of the Tübingen University 133 specimens of cervical carcinomas stages I and II operated on according to Wertheim-Meigs-Okabayashi. Topic of this analysis is lymph node status, concomitant alterations and lymphangiosis carcinomatosa. On the average 22.1 lymph nodes (1-58) have been removed. 12.8 per cent of cervical carcinomas had metastases, on the average 3 ones. 78.6 per cent of the metastases were localized in nondilymphatici interiliaci, 14.3 per cent in nodi iliaci communes. 5-year survival with metastases was 70.6 per cent, without 90.5 per cent. Over all a lymphangiosis carcinomatosa in 20.3 per cent was detectable. In 59.9 per cent of the lymph node metastases additionally a lymphangiosis carcinomatosa was present, on the contrary only 9.9 per cent of tumour-free ones. 5-year survival with lymphangiosis carcinomatosa was 70.4 per cent and 92.4 per cent without. Regressive changes, mostly as vacat fat, were observed in like the same percentage both in tumour positive and tumourfree lymph nodes.