Andree Faridi

Her-2/neu Gene Amplification and Protein Expression in Primary Male Breast Cancer

The role of HER-2/neu in male breast cancer is not well defined. The purpose of the current study was to measure the frequency of HER-2/neu expression in primary male breast cancer, to demonstrate HER-2/neu gene amplification in cases found to be positive for protein overexpression, and to correlate HER-2/neu positivity with clinicopathological variables. Formalin-fixed, paraffin-embedded archival material from 99 primary male breast carcinomas was evaluated by immunohistochemistry (IHC) using the HercepTest™ (DAKO Corp., Hamburg, Germany). Scoring was performed according to established guidelines. All cases demonstrating HER-2/neu staining by IHC (1+/2+ and 3+) were analyzed for HER-2/neu gene amplification by fluorescence in situ hybridization (FISH) utilizing the PathVysion™ assay (Vysis Corp., Downers Grove, Illinois) to assess HER-2/neu amplification status. The immunohistochemical staining of the HER-2/neu protein revealed HER-2/neu positivity in 15/99 (15.1%) cases, eight tumors showed 2+ and 7 tumors 3+ staining. HER-2/neu gene amplification was observed in 11/99 cases (11,1%), and all of the 3+ and 4/8 from the 2+ cases were amplified. HER-2/neu gene amplification/protein overexpression did not correlate with tumor state, histological grade or estrogen/progesterone receptor status nor the axillary lymph node status. This is the first comprehensive study of HER-2/neu gene amplification by FISH analysis in primary male breast cancer. Compared to female primary breast cancer the percentage of HER-2/neu positivity in our study was lower. Our data provide first evidence for HER-2/neu gene amplification in male breast cancer. Further studies should be addressed on the potential application of the monoclonal rhuMAB HER-2/neu antibody for treatment of HER-2/neu positive male breast cancer.

Anal sphincter injury during vaginal delivery--an argument for cesarean section on request?

Abstract Aims: Fear of damage to the pelvic floor from vaginal delivery and long-term sequelae (urinary and anal incontinence) sometimes being cited as an indication for cesarean section on request. The aim of the present study was to compare the effects of vaginal delivery versus elective cesarean section on anal sphincter function. Material and methods: We studied 71 consecutive women six weeks before delivery, 52 of them 4–6 weeks after delivery, and all patients with occult sphincter lesions 3months after delivery. A bowel function questionnaire was completed, and anal endosonography, manometry, and measurement of the pudendal-nerve terminal motor latency were performed. Results: Forty-two (80,8 percent) patients were delivered vaginally, ten (19,2 percent) by elective cesarean section at term. Clinically recognized anal sphincter injuries occurred in 9.5 percent (4) of patients, two of them developed incontinence for gas. The overall incidence of anal incontinence after vaginal delivery was 4.8 percent. Occult sphincter defects were identified endosonographically in 19 percent (8) of women, there was no reported case of any anal incontinence 3 months after delivery. No woman delivered by cesarean section had altered anal continence or any significant change in anal pressures, rectal sensibility, and PNTML. Conclusion: Severe sphincter tear is the single most important factor leading to anal incontinence in women, whereas occult sphincter defects are rarely associated with short-term sequelae, but may predispose to the development of anal incontinence later on in life. Elective cesarean section should be recommended for women at increased risk for anal incontinence.

Long-term Follow-up and Prognostic Significance of Angiogenic Basic Fibroblast Growth Factor (bFGF) Expression in Patients with Breast Cancer

The development of distant metastasis in breast cancer patients is the key step towards worse prognosis. The angiogenic basic fibroblast growth factor (bFGF) has been associated with tumorigenesis and metastasis in several human cancers. Therefore, bFGF expression was studied by immunohistochemistry in 111 patients with primary breast cancer. The results were correlated with prognostically relevant clinico-pathological features. such as tumor stage, grading. nodal stage and survival. bFGF was expressed in approximately 70% of the breast cancer tissues; 30% of the tumors showed strongly positive staining. With the exception of histological grading (p < 0.05), no correlation was found between the extent of bFGF expression and prognostic parameters. Analysis of survival showed a significantly (p < 0.05) prolonged survival for patients with a concomitant absence of axillary lymph node metastasis and bFGF immunoreactivity. Our data suggest that increased bFGF expression is a novel parameter for worse prognosis in nodal-negative breast cancer patients.

A whole blood flow cytometric determination of platelet activation by unfractionated and low molecular weight heparin in vitro

The influence of unfractionated (Heparin-Natrium) and low-molecular heparin (Fragmin(R)) on platelet activation in whole blood was investigated by FACS analysis in vitro using antibodies against glycoprotein (gp) IIb/IIIa (CD 41), GMP 140 (CD 62P), gp 53 (CD 63) and fibrinogen. Samples were also labeled with anti-gp Ib (CD 42b). Neither unfractionated heparin (UFH) nor low molecular weight heparin (LMWH) led to significant (i.e., p<0.05) changes in fluorescence intensities of platelets labeled with anti-gp IIb/IIIa or anti-gp 53. Significant platelet activation due to unfractionated heparin could be observed by labeling with anti-GMP 140 (UFH: p=0.009; LMWH: p=0.16). The proportion of platelets with surface-bound fibrinogen was significantly increased (UFH: p=0.00006; LMWH: p=0.008). After incubation with heparins, activation ability of platelets by adenosine diphosphate (ADP) was significantly increased. The potentiating action of unfractionated heparin was larger. Therefore, flow cytometric results of platelet activation in patients receiving heparin should be interpreted carefully.

Neonatal platelet activation in preeclampsia.

Preeclampsia is associated with an increased platelet activation, however, there are few studies concerning platelet activation of the newborn. The aim of our study was to compare platelet activation in newboms of preeclamptic mothers to newborns of healthy mothers by using whole blood flow cytometry. Blood samples were obtained from 20 newborns (10 healthy controls, 10 cases of preeclampsia/HELLP [hemolysis, elevated liver enzymes, and low platelet count] syndrome) during cesarean section. Antibodies against the following antigens were used as markers for platelet activation: CD 41, CD62P, CD 63, and platelet-bound fibrinogen. In addition to the basal platelet activation, the ability of platelets to undergo activation as a result of in vitro incubation with a weak agonist (adenosine diphosphate) was evaluated. A significant difference between the groups concerning basal platelet activation could only be seen for platelet-bound fibrinogen; the control group showed a higher extent of platelet activation (16.6 ± 11.3 vs. 6. 1 ± 4.9; p = 0.03). Incubation with adenosine diphosphate in the control group resulted in minor increases of platelet activation, which was significant only for platelet-bound fibrinogen (16.6± 11.3 vs. 42.5 ± 22.1; p = 0.02). However, the preeclamptic group showed significantly increased levels of platelet activation for all used markers after in vitro activation (CD 41 : 115.6 ± 18.2 vs. 163.2 ± 29.6; p = 0.002; CD62P: 2.4 ± 0.4 vs. 3.9 ± 0.3; p < 0.001; CD 63: 2.7 ± 0.5 vs. 3.7 ± 0.6; p = 0.002; platelet-bound fibrinogen: 6.1 ± 4.9 vs. 55.1± 9.1; p < 0.001). Preeclampsia or HELLP syndrome is therefore associated with an increased susceptibility to neonatal platelets, even against weak activators such as adenosine diphosphate. Whether this results from peculiarities in the fetal vascular environment or maternal influences is yet uncertain.

Treatment with Combinations of the Anti-HER2 Antibody Trastuzumab and Capecitabine in Advanced Metastatic Breast Cancer Patients - a Pilot Study

Background: Metastatic HER2-overexpressing breast cancer patients mostly are intensively pretreated patients. Tumor progression requires an effective and well tolerated treatment. Here, we report of a study with capecitabine/trastuzumab combination therapy, with regard to tumor response and safety in advanced metastatic breast cancer overexpressing HER2. Patients and Methods: A cohort of 20 metastatic patients suffering from HER2-overexpressing carcinoma were treated with capecitabine/trastuzumab. The patients had progressive disease after taxane/trastuzumab combination therapy. All patients received a standard dose of capecitabine 1,250 mg/m2 twice daily, administered on days 1-14, combined with 2 mg/kg weekly trastuzumab. Trastuzumab treatment was continued from previous treatment regimens. Safety and tolerability of this regimen were evaluated. Results: Response rate and time to progression were documented. The median number of treatment cycles was 10 (range: 3-18). The median dose of capecitabine was 2,100 mg/m2 daily. 2 patients were reported to have complete response, 6 partial response, and 5 stable disease. 7 patients had progressive disease. Median time to progression was 30 weeks. The treatment was well tolerated with little side effects. Only palmar-plantar erythema and gastrointestinal disorders required dose reductions. Conclusion: Combination of capecitabine/trastuzumab is an effective and safe regimen in pretreated HER2-positive metastatic breast cancer. Our results comfirm preclinical observations of an at least additive effect of HER2 antibody treatment with capecitabine.

Histologische Befunde an Silikonimplantat-Kapseln der Brust in Abhängigkeit von der Liegezeit

Objective: The aim of this histological investigation of capsular tissue adjacent to silicone breast implants is to describe the time-dependent nature of changes in the fibrous implant capsule. Methods: Forty-one silicone breast implants were removed from 31 patients. The patients had a median age of 53.6 years. Twenty-three implants had smooth surfaces and 18 implants had textured surfaces. Implants and capsules were removed completely in every case. After analysis of the implant capsule, capsular thickness, signs of cellular inflammation, calcifications in the implant capsule, the presence of silicone degradation products and a synovia-like metaplasia are described. Results: Depending on the implant duration we found silicone degradation products in 32% of the capsules. Signs of cellular inflammation were recognised in 49.5% of the capsules without correlation to implant duration. Synovia-like metaplasia occurred mainly in the early implant period (p<0.001) and was more frequent around textured implants. Histological results in older implants are a greater capsular thickness (p < 0.001), calcification (p <0.001) and the clinical occurrence of a capsular contraction. Conclusions: In summary, the histologic changes around implants seem to be dynamic in nature, and implant duration and shell type play a significant role.

Das Plattenepithelkarzinom des kleinen Beckens nach zurückliegender Hysterektomie bei Benignität des Uterus - Kasuistiken und differenzialdiagnostische Darstellung

We describe two patients with disseminated squamous cell carcinoma in the pelvis 14 and 22 years after hysterectomy for benign reasons. Tumor spread was consistent with squamous cell carcinoma of the cervix. Both patients underwent complete surgical removal of all gross tumor and received postoperative radiochemotherapy. The differential diagnosis of squamous cell carcinoma in the pelvis after remote hysterectomy for benign indications includes recurrent cancer of the cervix or endometrium, vaginal cancer, squamous cell carcinoma of the ovary, and carcinoma arising from squamous metaplasia of the urogenital tract.

Anorektale Inkontinenz als Folge der vaginalen Geburt

Obstetric trauma is the most common cause of anal incontinence in women. Incontinence is usually for gas, but some women are incontinent of solid or liquid stool. Women are frequently too embarrassed by anal incontinence to raise the issue with a physician. Vaginal delivery can result in direct muscular injury to the anal sphincter and indirect neurologic injury to the pelvic floor. Anal endosonography has shown a 30% rate of occult sphincter defects in women after their first vaginal delivery. About a third of these women develop anal incontinence or urgency, but the long-term clinical significance of these findings is unclear. Routine mediolateral episiotomy does not protect against anal sphincter trauma and midline episiotomy is associated with an increased rate of sphincter tears. Overall, anal sphincter tears occur at 0.4% to 7% of deliveries. About 19% to 58% of these women are incontinent at 6 months and symptoms can persist in up to 30%. Subsequent vaginal deliveries after an anal sphincter tear 1 increase the risk of anal incontinence. Elective cesarean delivery should be discussed with women with a persistent sphincter defect or transient fecal incontinence. Cesarean delivery is not associated with clinically significant long-term pelvic floor morbidity. Methods to prevent perineal trauma during vaginal delivery include restricting episiotomy and using vacuum extraction instead of forceps delivery, Obstetricians should be aware of the prevalence of and risk factors for the development of fecal incontinence and ask patients specifically about urinary and anal incontinence.