Cancer cells induce interleukin-22 production from memory CD4+ T cells via interleukin-1 to promote tumor growth.

IL-22 has been identified as a cancer-promoting cytokine that is secreted by infiltrating immune cells in several cancer models. We hypothesized that IL-22 regulation would occur at the interface between cancer cells and immune cells. Breast and lung cancer cells of murine and human origin induced IL-22 production from memory CD4+ T cells. In the present study, we found that IL-22 production in humans is dependent on activation of the NLRP3 inflammasome with the subsequent release of IL-1ß from both myeloid and T cells. IL-1 receptor signaling via the transcription factors AhR and RORγt in T cells was necessary and sufficient for IL-22 production. In these settings, IL-1 induced IL-22 production from a mixed T helper cell population comprised of Th1, Th17, and Th22 cells, which was abrogated by the addition of anakinra. We confirmed these findings in vitro and in vivo in two murine tumor models, in primary human breast and lung cancer cells, and in deposited expression data. Relevant to ongoing clinical trials in breast cancer, we demonstrate here that the IL-1 receptor antagonist anakinra abrogates IL-22 production and reduces tumor growth in a murine breast cancer model. Thus, we describe here a previously unrecognized mechanism by which cancer cells induce IL-22 production from memory CD4+ T cells via activation of the NLRP3 inflammasome and the release of IL-1ß to promote tumor growth. These findings may provide the basis for therapeutic interventions that affect IL-22 production by targeting IL-1 activity.

Dual-energy CT for the evaluation of silicone breast implants.

OBJECTIVE: The evaluation of breast implants for rupture is currently the domain of ultrasound and MRI, while mammography is of very limited diagnostic value. Recently, specific visualisation of silicone has become feasible using dual-energy CT. Our objective was to evaluate whether it is feasible to identify silicone in breast implants by dual-energy CT and to reliably diagnose or rule out ruptures. METHODS: Seven silicone breast implant specimens were examined on dual-source CT at 100- and 140-kV tube potential with a 0.8-mm tin filter (collimation 128 × 0.6 mm, current-time products 165 and 140 mAsref with modulation, rotation time 0.28 s, pitch 0.55). Two patients scheduled for implant removal or replacement were examined with identical parameters. RESULTS: The silicone of the implant specimens showed a strong dual-energy signal. In one patient, both implants were intact, while a rupture was identified in the other patient. Ultrasound, MRI, surgical findings and histology confirmed the dual-energy CT diagnosis. CONCLUSION: Dual-energy CT may serve as an alternative technique for speedy evaluation of silicone breast implants. Specific clinical studies are required to determine the diagnostic accuracy and define indications for this technique.

Acceptance of routine or case-based inquiry for intimate partner violence: a mixed method study.

BACKGROUND: The prevalence and detrimental health effects of intimate partner violence have resulted in international discussions and recommendations that health care professionals should screen women for intimate partner violence during general and antenatal health care visits. Due to the lack of discussion on routine or case-based inquiry for intimate partner violence during antenatal care in Germany, this study seeks to explore its acceptability among pregnant German women. METHODS: A mixed methods approach was used, utilizing a self-administered survey on the acceptability of routine or case-based inquiry for intimate partner violence in a university hospital's maternity ward in Munich and in-depth interviews with seven women who experienced violence during pregnancy. RESULTS: Of the 401 women who participated in the survey, 92 percent were in favor of routine or case-based inquiry for intimate partner violence during antenatal care. Acceptance of routine or case-based inquiry for intimate partner violence during antenatal care was significantly associated with women's experiences of child sexual abuse, being young, less educated, single or divorced and smoking during pregnancy. Open-ended survey questions and in-depth interviews stressed adequate training for screening, sufficient time and provision of referral information as important conditions for routine or case-based inquiry for intimate partner violence. CONCLUSIONS: Women in this study showed an overwhelming support for routine or case-based screening for intimate partner violence in antenatal care in Germany. Until adequate training is in place to allow providers to inquire for intimate partner violence in a professional manner, this study recommends that health care providers are made aware of the prevalence and health consequences of violence during pregnancy.

Bilateral prophylactic skin-reducing nipple-sparing mastectomy with immediate breast reconstruction using only a vascularized dermal-subcutaneous pedicle: technique and possible advantages.

PURPOSE: To present a new surgical technique regarding breast reconstruction after skin-reducing nipple-sparing mastectomy. METHOD: The current trend for immediate breast reconstruction after skin-reducing mastectomy mainly supports the insertion of subpectoral implants or the use of autologous breast reconstruction techniques. Herein for the first time, we present a case of bilateral prophylactic skin-reducing nipple-sparing mastectomy with immediate breast reconstruction, using only a dermal-cutaneous pedicle. RESULTS: The postoperative course was uneventful. Forty days postoperatively the aesthetic result was excellent. CONCLUSIONS: We believe that such technique in selected cases can present several advantages as low cost, reduced possibilities for complications associated to implant insertion or autologous reconstruction techniques and an easier mammography follow-up.

A retrospective investigation of women's experience with breast reconstruction after mastectomy.

PURPOSE: A diagnosis of breast cancer is often accompanied by the fear of loss of previous body image and attractiveness. Hence, many patients opt for reconstructive surgery. This study evaluated the effects of different types of reconstructive surgery after mastectomy on the functional and psychological adjustment of patients. METHODS: In a cohort study, patients, who had breast reconstruction after mastectomy by means of four different allogenic or autologues techniques between 1999-2006 were retrospectively interviewed in person or by telephone. The questions addressed complication rates, physical complaints, functional impairments, body image outcomes, sexuality and patient satisfaction. RESULTS: Of 139 patients, 89 (64.7 %) completed the survey. 32 (35.9 %) patients experienced one or more postoperative complications like seroma, hematoma, infections or necrosis. 16 (20 %) and 13 (16 %) patients reported strong and moderate adverse effects on sexuality, respectively. 62 (70 %) patients indicated that they were actively included in the decision making process. Patient ratings of good or bad medical advice were associated with complication rates (p = 0.008). Patients, who evaluated their first preoperative counseling positively, reported higher consent rates when a re-reconstruction became necessary (p ≤ 0.001). Satisfaction with the functional outcome after reconstruction and satisfaction with the cosmetic result was highly correlated (p < 0.001). CONCLUSIONS: A significant association of patient satisfaction with postoperative complications and the decision for a re-reconstruction was demonstrated. Furthermore, our results emphasize the importance of detailed preoperative counseling for women's adjustment to reconstructive surgery.

Steroid hormone receptor expression in ovarian cancer: progesterone receptor B as prognostic marker for patient survival.

BACKGROUND: There is partially conflicting evidence on the influence of the steroid hormones estrogen (E) and progesterone (P) on the development of ovarian cancer (OC). The aim of this study was to assess the expression of the receptor isoforms ER-α/-ß and PR-A/-B in OC tissue and to analyze its impact on clinical and pathological features and patient outcome. METHODS: 155 OC patients were included who had been diagnosed and treated between 1990 and 2002. Patient characteristics, histology and follow-up data were available. ER-α/-ß and PR-A/-B expression were determined by immunohistochemistry. RESULTS: OC tissue was positive for ER-α/-ß in 31.4% and 60.1% and PR-A/-B in 36.2% and 33.8%, respectively. We identified significant differences in ER-ß expression related to the histological subtype (p=0.041), stage (p=0.002) and grade (p=0.011) as well as PR-A and tumor stage (p=0.03). Interestingly, median receptor expression for ER-α and PR-A/-B was significantly higher in G1 vs. G2 OC. Kaplan Meier analysis revealed a good prognosis for ER-α positive (p=0.039) and PR-B positive (p<0.001) OC. In contrast, ER-ß negative OC had a favorable outcome (p=0.049). Besides tumor grade and stage, Cox-regression analysis showed PR-B to be an independent prognostic marker for patient survival (p=0.009, 95% CI 0.251-0.823, HR 0.455). CONCLUSION: ER-α/-ß and PR-A/-B are frequently expressed in OC with a certain variability relating to histological subtype, grade and stage. Univariate analysis indicated a favorable outcome for ER-α positive and PR-B positive OC, while multivariate analysis showed PR-B to be the only independent prognostic marker for patient survival. In conclusion, ER and PR receptors may be useful targets for a more individualized OC therapy.

Intimate partner violence and its association with pregnancy loss and pregnancy planning.

OBJECTIVE: To examine the effect of physical partner violence on pregnancy loss and unplanned pregnancy. DESIGN: Cross-sectional, self-reported questionnaire survey. SETTING: A maternity ward of a university hospital in Munich, Germany. SAMPLE: Women who gave birth within the previous seven days. METHODS: The effects of physical partner violence on pregnancy loss and unplanned pregnancy were estimated using descriptive statistics based on χ(2) tests, bivariate logistic regression and multivariate logistic regression. MAIN OUTCOME MEASURES: Physical partner violence was assessed using the Abuse Assessment Screen, information on pregnancy loss was derived from women's medical files and the assessment of pregnancy planning was based on women's self-reports. RESULTS: The survey had a response rate of 73%; 29% of the women experienced pregnancy loss, 13% reported that their last pregnancy was unplanned and 4% revealed physical violence by a current or previous partner. Physical partner violence was significantly associated with pregnancy loss (odds ratio 8.33, 95% confidence interval 2.01-34.59) and unplanned last pregnancy (odds ratio 5.03, 95% confidence interval 1.21-21.26), even after adjusting for other commonly known explanatory factors, such as number of children, women's age and women's and their partners' education level and employment, marital status, financial situation and support during pregnancy. CONCLUSIONS: Physical partner violence is an important factor in understanding pregnancy loss and unplanned pregnancy. Inquiring about the existence of intimate partner violence among these women might help to identify women in need of domestic violence services.

Late Presentation at Primary Diagnosis of Breast Cancer: Patients' Personality Characteristics and Attitudes.

INTRODUCTION: Breast cancer (BC) is the most common cancer in women worldwide. Despite screening and information efforts, about 10% of patients present with tumor size T3 or T4 at primary diagnosis. Late presentation is associated with more advanced tumor stage and consecutively with worse survival rates. OBJECTIVE: This study aimed to evaluate whether patients with a late presentation at primary BC diagnosis differ in their personality from those with early diagnosis. METHODS: In this bicentric, observational study, personality traits, positive and negative affectivity, anxiety, spirituality, illness beliefs, and sociodemographic characteristics were assessed in BC patients who presented with T-stages 3 or 4 (late presenters) and T-stages 1 or 2 (controls) at initial diagnosis. RESULTS: Forty patients (20 controls, 20 late presenters) were interviewed. "Late presenters" perceived their disease as long lasting and had significantly more "positive affectivity" in the current trait. Although no significant associations were found, there was a trend for late presenters to have higher education levels, less spiritual longing, less accurate explanation of their illness, less anxiety in the trait scale, and more conscientiousness than the controls. CONCLUSION: As patients with late presentation for BC differ in specific psychological and sociodemographic characteristics from patients with early BC, the findings of this pilot project warrant additional investigations to identify further specific characteristics and motivations. Identifying patients at risk for late presentation and encouraging them to accept an earlier diagnosis could help to improve their therapy and, finally, their outcome.

Worldwide first experiences with vacuum-assisted closure as alternative treatment method to repair defects of an extended thoracic wall recurrence of breast cancer.

INTRODUCTION: Loco-regional recurrences of the breast cancer are associated with a bad prognosis. Often costly autologous-tissue treatment as a surgery aiming at repairing the defects is necessary. PATIENTS AND METHODS: Four female patients were treated with the vacuum-assisted closure (VAC)-system in context with the recurrence resection. In all cases a primary local masking was not possible. RESULTS: In the described cases the wounds healed well during the post-operative phase. There occurred no problems either during the radiation treatment or during chemotherapy in the case of lying VAC-Systems. CONCLUSION: Using vacuum-assisted wound closure one can avoid autologous-tissue treatment in the case of extensive loco-regional recurrences.

Phyllodes tumour of the breast: clinical follow-up of 33 cases of this rare disease.

OBJECTIVE: The "cystosarcoma phyllodes" of the breast is a rare entity which accounts for 0.5% of all breast neoplasms. The aim of our study was to analyse the clinical management with respect to patient outcome. STUDY DESIGN: The data of 5270 patients with primary breast neoplasms treated in our department between 1984 and 2005 were retrospectively analysed for the histopathologic diagnosis of a cystosarcoma phyllodes. The clinical data was analysed with respect to tumour grading and size, treatment and prognosis. RESULTS: Retrospective analysis of 5270 patients with primary breast neoplasms revealed 33 patients. In the histopathological analysis, tumour grade was classified as benign in 40%, borderline in 27% and malignant in 33% of patients. Breast conserving surgery was conducted in 58% of the patients, mastectomy in 42%. Only one patient was treated with adjuvant radiotherapy after primary surgery. Mean tumour size was 6.9 cm, and no lymph node infiltration was found in the 10 patients who received axillary lymph node dissection. Local recurrence occurred in eight patients (26%). The local recurrence rate was 50% in malignant, 20% in borderline and only 8% in benign tumours. Distant metastases were seen in three patients (9%) with malignant phyllodes tumours. Neither regarding age at primary diagnosis nor in tumour size there was a significant difference between patients with local recurrence or metastatic spread and those without (p=0.284 tumour size; p=0.739 for age; Mann-Whitney U-test). CONCLUSION: Histopathological classification appears to be the strongest prognostic factor in this disease.

The risk of non-sentinel metastases in primary breast cancer.

BACKGROUND: Sentinel node biopsy (SNB) has been established as standard of surgical care in primary breast cancer. If the sentinel node (SN) is negative, axillary dissection (ALND) is not necessary, but if the SN is positive ALND is warranted. This analysis evaluated associated risk factors for non-sentinel metastases in the case of a positive SN. PATIENTS AND METHODS: A retrospective analysis of all SNB performed between 10/1999 and 07/2005 was carried out. RESULTS: A total of 406 patients were included: 214 patients (51%) had SNB with ALND while 197 patients (49%) had SNB only. In 41 of 109 nodal-positive patients, the SN was the only nodal metastasis. In the multivariate analysis, the number of positive SN and the presence of lymphatic vessel infiltration were significant risk factors for additional non-sentinel metastases (p = 0.05 and 0.047, respectively). The risk for non-sentinel metastases was 25.9% without and 59.2% with these risk factors, respectively. CONCLUSION: If the SN is positive, ALND remains obligatory.

Obstetrical and gynecological writing and publishing in Europe.

OBJECTIVE: To assess the number and quality of scientific articles published by authors from the European Union (EU) and Germany in the field of obstetrics and gynecology. STUDY DESIGN: Scientific articles published during the years 1980-2003 covered by the Journal Citation Report (JCR) were considered, with a focus on the impact factor (IF), authors' origin, journal country and publishing language. RESULTS: In 2003, there are 53 journals listed by the JCR for the field category 'obstetrics and gynecology', with altogether 3201 publications listed in the Science Citation Index (SCI). From the year 1980, the total number of publications increased persistently. Looking at the top 20 journals in the field of obstetrics and gynecology, there are 12 journals from the US, 8 from Europe. None of these journals has an IF>10 but 30 journals show an IF>1. Over the last 25 years, a growing importance of the English language as scientific language can be observed. CONCLUSION: These data indicate an important role of European research in the field of obstetrics and gynecology comparable to that of US-American research. The English language is gaining importance as scientific language, displacing other languages and contributing to a loss of impact of non-English journals.

Local Resection of Primary Tumor in Upfront Stage IV Breast Cancer.

BACKGROUND: This study aimed to identify the association of local surgery of the primary tumor in metastatic breast cancer (MBC) patients with overall survival (OS) and prognostic factors. PATIENTS AND METHODS: Patients with primary MBC (1990-2006) were included in our retrospective analysis (n = 236). 83.1% had surgery for the primary tumor. OS was evaluated using Kaplan-Meier estimates. Predictive factors for OS were determined. RESULTS: Median follow-up was 123 months for all patients still alive at the time of analysis. In univariate analysis, patients with surgery of the primary tumor had significantly prolonged OS (28.9 vs. 23.9 months). Within the surgery group, patients with MBC limited to 1 organ system had a better outcome (39.3 vs. 24.9 months), as did asymptomatic patients. Independent risk factors for shorter OS were hormone receptor negativity, symptoms, and involvement of ≥ 1 organ system. CONCLUSION: Patient selection for local therapy was confounded by a more favorable profile and a lesser tumor burden before surgery, which might implicate a bias. Nevertheless, our univariate results indicate that local surgery of the primary tumor in MBC patients could be considered as part of the therapeutic regimen in selected patients. However, larger patient numbers are needed to prove these findings in the multivariate model.

[Sentinel lymph node biopsy in breast cancer: state of the art]. / Die Sentinellymphknoten-Entfernung beim Mammakarzinom: Derzeitiger Stand.

Axillary lymph node excision of level I and II with at least 10 lymph nodes is the operative gold standard for invasive breast cancer. Axillary lymph node excision is a diagnostic procedure for histopathologic tumor classification, for assessment of prognosis, local tumor control and adjuvant therapy decision. The sentinel node biopsy is a minimal-invasive procedure to determine the axillary lymph node status by excision of one or more sentinel nodes. This procedure is being increasingly implemented in breast cancer surgery. The classical axillary lymph node excision can be replaced by sentinel node biopsy if sentinel nodes are free of invasion in the intraoperative as well as in the final histopathological report. Sentinel node biopsy can become an operative routine procedure only in a quality-controlled environment.

Thyroid hormone receptor (TR)alpha and TRbeta expression in breast cancer.

UNLABELLED: There is evidence that breast cancer patients suffer from thyroid disorders. However, the relation between thyroid receptor (TR) expression and breast cancer remains unknown so far. Therefore, the aim of this study was an immunohistochemical analysis of TR expression in breast cancer patients. MATERIALS AND METHODS: The expression of the combined antibody TRalpha1 and 2 and TRalpha1 or 2 alone as well as the expression of combined TRbeta1 and 2 and TRbeta1 or 2 alone was investigated with specific monoclonal or polyclonal antibodies in 82 patients. All patients presented with a first diagnosis of sporadic breast cancer. The ABC method was used for staining and staining intensities were analyzed using the IRS score. RESULTS: Both TRalpha and TRbeta were expressed in the nuclei of breast cancer cells. In 24% (28/78) of the slides TRalpha1 and 2 IRS was positive. Immunopositivity for TRalpha1 was found in 55/78 slides, for TRalpha 2 in 54/79 slides (71 and 68%, respectively). The expression of TRbeta1 and 2 showed a positive detection in 33/77 (43%) of the slides, for TRbeta1 it was 43/79 (54%), for TRbeta2 60/76 (79%). Significant correlations of the expression of TRs - especially TRalpha2 - were found with further prognostic histopathological parameters such as tumor size, axillary lymph node involvement, grading and hormone receptor status. Multivariate analysis showed a trend for TRalpha2 as an independent predictor of disease-free and overall survival. DISCUSSION: Our results revealed specific alterations in the expression of TRs - especially of TRalpha2 - in breast cancer patients, suggesting it as a marker with possible prognostic validity.