Treatment and outcome in metastatic lobular breast cancer in the prospective German research platform OPAL.

PURPOSE: Evidence about routine treatment and outcome of patients with invasive lobular cancer (ILC) is limited, especially regarding metastatic disease. Here we present prospective real-world data of patients with metastatic ILC (mILC) as compared to patients with metastatic invasive ductal cancer (mIDC) receiving systemic therapy in routine care in Germany. METHODS: Prospective data on patient and tumor characteristics, treatments, and outcomes of patients with mILC (n = 466) and mIDC (n = 2100), recruited between 2007 and 2021 into the Tumor Registry Breast Cancer/OPAL were analyzed. RESULTS: Compared to mIDCs, patients with mILC were older at start of first-line treatment (median 69 vs. 63 years) and had more often lower grade (G1/G2: 72.8% vs. 51.2%), hormone receptor (HR)-positive (83.7% vs. 73.2%) and less often HER2-positive (14.2% vs. 28.6%) tumors, which metastasized more frequently to the bone (19.7% vs. 14.5%) or peritoneum (9.9% vs. 2.0%), and less frequently to the lungs (0.9% vs. 4.0%). Median OS of patients with mILC (n = 209) and mIDC (n = 1158) was 30.2 months [95% confidence interval (CI) 25.3, 36.0] and 33.7 months [95% CI 30.3, 37.9], respectively. Multivariate survival analysis did not show a significant prognostic impact of the histological subtype [HR mILC vs. mIDC 1.18 (95% CI 0.97-1.42)]. CONCLUSION: Overall, our real-world data confirm clinicopathological differences between mILC and mIDC breast cancer patients. Despite patients with mILC presenting with some favorable prognostic factors, ILC histopathology was not associated with a better clinical outcome in multivariate analysis, suggesting the need for more tailored treatment strategies for patients with the lobular subtype.

Pathologic complete response (pCR) to neoadjuvant treatment with or without atezolizumab in triple-negative, early high-risk and locally advanced breast cancer: NeoTRIP Michelangelo randomized study.

BACKGROUND: High-risk triple-negative breast cancers (TNBCs) are characterized by poor prognosis, rapid progression to metastatic stage and onset of resistance to chemotherapy, thus representing an area in need of new therapeutic approaches. Programmed death-ligand 1 (PD-L1) expression is an adaptive mechanism of tumour resistance to tumour-infiltrating lymphocytes, which in turn are needed for response to chemotherapy. Overall, available data support the concept that blockade of PD-L1/programmed cell death protein 1 checkpoint may improve efficacy of classical chemotherapy. PATIENTS AND METHODS: Two hundred and eighty patients with TNBC were enrolled in this multicentre study (NCT002620280) and randomized to neoadjuvant carboplatin area under the curve 2 and nab-paclitaxel 125 mg/m2 intravenously (i.v.) on days 1 and 8, without (n = 142) or with (n = 138) atezolizumab 1200 mg i.v. on day 1. Both regimens were given q3 weeks for eight cycles before surgery followed by four cycles of an adjuvant anthracycline regimen. The primary aim of the study was to compare event-free survival (EFS), and an important secondary aim was the rate of pathological complete response (pCR defined as the absence of invasive cells in breast and lymph nodes). The primary population for all efficacy endpoints is the intention-to-treat (ITT) population. RESULTS: The ITT analysis revealed that pCR rate after treatment with atezolizumab (48.6%) did not reach statistical significance compared to no atezolizumab [44.4%: odds ratio (OR) 1.18; 95% confidence interval 0.74-1.89; P = 0.48]. Treatment-related adverse events were similar with either regimen except for a significantly higher overall incidence of serious adverse events and liver transaminase abnormalities with atezolizumab. CONCLUSIONS: The addition of atezolizumab to nab-paclitaxel and carboplatin did not significantly increase the rate of pCR in women with TNBC. In multivariate analysis, the presence of PD-L1 expression was the most significant factor influencing the rate of pCR (OR 2.08). Continuing follow-up for the EFS is ongoing, and molecular studies are under way.

Strong impact of MammaPrint and BluePrint on treatment decisions in luminal early breast cancer: results of the WSG-PRIMe study.

PURPOSE: The WSG-PRIMe Study prospectively evaluated the impact of the 70-gene signature MammaPrint® (MP) and the 80-gene molecular subtyping assay BluePrint® on clinical therapy decisions in luminal early breast cancer. METHODS: 452 hormone receptor (HR)-positive and HER2-negative patients were recruited (N0, N1). Physicians provided initial therapy recommendations based on clinicopathological factors. After prospective risk classification by MammaPrint/BluePrint was revealed, post-test treatment recommendations and actual treatment were recorded. Decisional Conflict and anxiety were measured by questionnaires. RESULTS: Post-test switch (in chemotherapy (CT) recommendation) occurred in 29.1% of cases. Overall, physician adherence to MP risk assessment was 92.3% for low-risk and 94.3% for high-risk MP scores. Adherence was remarkably high in "discordant" groups: 74.7% of physicians initially recommending CT switched to CT omission following low-risk MP scores; conversely, 88.9% of physicians initially recommending CT omission switched to CT recommendations following high-risk MP scores. Most patients (99.2%) recommended to forgo CT post-test and 21.3% of patients with post-test CT recommendations did not undergo CT; among MP low-risk patients with pre-test and post-test CT recommendations, 40% did not actually undergo CT. Luminal subtype assessment by BluePrint was discordant with IHC assessment in 34% of patients. Patients' State Anxiety scores improved significantly overall, particularly in MP low-risk patients. Trait Anxiety scores increased slightly in MP high risk and decreased slightly in MP low-risk patients. CONCLUSIONS: MammaPrint and BluePrint test results strongly impacted physicians' therapy decisions in luminal EBC with up to three involved lymph nodes. The high adherence to genetically determined risk assessment represents a key prerequisite for achieving a personalized cost-effective approach to disease management of early breast cancer.

Somatic tinnitus prevalence and treatment with tinnitus retraining therapy.

OBJECTIVES: Somatic tinnitus originates from increased activity of the dorsal cochlear nucleus, a cross-point between the somatic and auditory systems. Its activity can be modified by auditory stimulation or somatic system manipulation. Thus, sound enrichment and white noise stimulation might decrease tinnitus and associated somatic symptoms. The present uncontrolled study sought to determine somatic tinnitus prevalence among tinnitus sufferers, and to investigate whether sound therapy with counselling (tinnitus retraining therapy; TRT) may decrease tinnitus-associated somatic symptoms. METHODS: To determine somatic tinnitus prevalence, 70 patients following the TRT protocol completed the Jastreboff Structured Interview (JSI) with additional questions regarding the presence and type of somatic symptoms. Among 21 somatic tinnitus patients, we further investigated the effects of TRT on tinnitus-associated facial dysesthesia. Before and after three months of TRT, tinnitus severity was evaluated using the Tinnitus Handicap Inventory (THI), and facial dysesthesia was assessed with an extended JSI-based questionnaire. RESULTS: Among the evaluated tinnitus patients, 56% presented somatic tinnitus-including 51% with facial dysesthesia, 36% who could modulate tinnitus by head and neck movements, and 13% with both conditions. Self-evaluation indicated that TRT significantly improved tinnitus and facial dysesthesia in 76% of patients. Three months of TRT led to a 50% decrease in mean THI and JSI scores regarding facial dysesthesia. CONCLUSIONS: Somatic tinnitus is a frequent and underestimated condition. We suggest an extension of the JSI, including specific questions regarding somatic tinnitus. TRT significantly improved tinnitus and accompanying facial dysesthesia, and could be a useful somatic tinnitus treatment.

Acute external ear lesions: clinical aspects, assessment and management.

Acute external ear lesions: clinical aspects, assessment and management. We reviewed the literature concerning the assessment and the management of the external ear traumas, which is not very rich. Nevertheless, we outlined the practical attitudes in the four major conditions met: the auricular haematoma, the auricular perichondritis, the auricular laceration and auricular bums. All these pathologies must be promptly treated because there is a risk of perichondritis, which can destroy the cartilage and will result in a severely deformed ear. Auricular haematomas must be drained as soon as possible, lacerations with exposed cartilage must be stitched urgently, and burnt ears should be washed, coated with alginates (Flaminal@) and covered with a loose dressing. Antibioprophyl- axy should always be prescribed after a complete microbiological sampling.

Red cell storage in E-Sol 5 and Adsol additive solutions: paired comparison using mixed and non-mixed study designs.

BACKGROUND AND OBJECTIVES: If transfusion of older stored red cells is found to negatively affect clinical outcome, one possible alternative to shortened outdate is the use of new additive solutions (AS) that ameliorate the storage lesion. Erythro-Sol (E-Sol), a previously developed next-generation AS, has been reformulated into E-Sol 5, which is compatible with current anticoagulants and AS volumes. The effect of E-Sol 5 on red cells during storage compared to current AS has not been reported. MATERIALS AND METHODS: Paired, ABO-matched whole-blood units were collected into CPD anticoagulant, pooled, split and processed into plasma and red cell units with either 110 ml of Adsol or 105 ml of E-Sol 5 within 8 h of collection. In Study 1, paired units in E-Sol 5 and Adsol were sampled on Day 0 and every 7 days up to Day 42 (n = 10). In Study 2, paired units in E-Sol 5 and Adsol were sampled only on Day 0 and Day 42 (n = 10). RESULTS: In Study 1, 2,3 DPG levels were maintained until Day 28 in E-Sol 5 units and Day 14 in Adsol units. ATP levels were higher in E-Sol 5 units until Day 21, after which they were comparable between the two groups. In both studies, metabolic activity was greater in E-Sol 5 units with respect to glucose consumption and lactate production. Morphology scores were higher, and haemolysis and microparticles generated were lower in E-Sol 5 vs. Adsol units. Weekly mixing of units lowered haemolysis and microparticle levels and increased potassium content on Day 42 in both additive solutions. CONCLUSION: Regardless of whether units are mixed weekly or are stored non-mixed, E-Sol 5 slows the progression of the red cell storage lesion and improves the overall in vitro quality of RBC throughout storage.

Breast cancer--new aspects of tumor biology: are calcitriol and cyclooxygenase-2 possible targets for breast cancer?

Up until now there have been many advances in treatment options for breast cancers such as targeted therapies like monoclonal antibodies, tyrosine kinase inhibitors, mTOR antagonists, and vaccines. Despite these advances, there are still many more that warrant further exploration. Two of these targets might be the cyclooxygenase-2 (COX-2), the key enzyme required to convert arachidonic acid to prostaglandins, and calcitriol [1,25(OH)2D3] which is the biologically active form of vitamin D. Both calcitriol and the inhibition of COX-2 have shown antiproliferative and prodifferentiation, as well as pro-apoptotic effects in different malignancies in vitro and in vivo, and the key prostaglandin catabolic enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is known to have tumor suppressor activity. Furthermore, the combination ofcalcitriol and nonsteroidal anti-inflammatory drugs (NSAIDs), such as non-selective and selective COX-2 inhibitors, acting synergistically to achieve significant cell growth inhibition in prostate cancer. Some epidemiological studies suggest that vitamin D confers a moderate benefit against breast cancer while most epidemiological studies presume that NSAIDs confer the same. Nevertheless there is growing body of evidence that COX-2 expression is a fundamental step in breast cancer carcinogenesis. To date, clinical trials have been conducted in patients with different malignancies using treatment strategies including COX-2 inhibitors and calcitriol and are showing partially encouraging results. The goal of this review is to shed light on the association between the prostaglandin as well as vitamin D metabolism relating to the incidence and therapy of breast cancers. Moreover, this review will also highlight potential treatment options, as well as extract any existing interactions between the two metabolisms.

[Assessment of hypoacusis]. / Mise au point d'une hypoacousie.

Hypoacusis is a common complaint among young and older patients. This common symptom addressed in general medicine is often but not always due to a benign disease; sometimes, life-threatening emergencies occur and must be recognised. Moreover, hypoacusis is known to lead to social isolation and nervous breakdown among old people, and to slow down speech learning among children. Unfortunately, the general practitioner is not tooled to assess accurately the hard-of-hearing patient, but nevertheless, he can get easily a first differential diagnosis. First of all, comprehensive history and clinical exam can be quickly carried out. In particular cases, specialised investigations and ENT consultations are indicated. That is why this article is built to answer basic questions to frequent clinical problems involving a reduced audition, and to suggest first-line recommendations.

Long-term survival of breast cancer patients with brain metastases: subanalysis of the BMBC registry.

BACKGROUND: Up to 30% of metastatic breast cancer (BC) patients develop brain metastases (BM). Prognosis of patients with BM is poor and long-term survival is rare. Identification of factors associated with long-term survival is important for improving treatment modalities. PATIENTS AND METHODS: A total of 2889 patients of the national registry for BM in BC (BMBC) were available for this analysis. Long-term survival was defined as overall survival (OS) in the upper third of the failure curve resulting in a cut-off of 15 months. A total of 887 patients were categorized as long-term survivors. RESULTS: Long-term survivors compared to other patients were younger at BC and BM diagnosis (median 48 versus 54 years and 53 versus 59 years), more often had HER2-positive tumors (59.1% versus 36.3%), less frequently luminal-like (29.1% versus 35.7%) or triple-negative breast cancer (TNBC) (11.9% versus 28.1%), showed better Eastern Cooperative Oncology Group (ECOG) performance status (PS) at the time of BM diagnosis (ECOG 0-1, 76.9% versus 51.0%), higher pathological complete remission rates after neoadjuvant chemotherapy (21.6% versus 13.7%) and lower number of BM (n = 1, BM 40.9% versus 25.4%; n = 2-3, BM 26.5% versus 26.7%; n ≥4, BM 32.6% versus 47.9%) (P < 0.001). Long-term survivors had leptomeningeal metastases (10.4% versus 17.5%) and extracranial metastases (ECM, 73.6% versus 82.5%) less frequently, and asymptomatic BM more often at the time of BM diagnosis (26.5% versus 20.1%), (P < 0.001). Median OS in long-term survivors was about two times higher than the cut-off of 15 months: 30.9 months [interquartile range (IQR) 30.3] overall, 33.9 months (IQR 37.1) in HER2-positive, 26.9 months (IQR 22.0) in luminal-like and 26.5 months (IQR 18.2) in TNBC patients. CONCLUSIONS: In our analysis, long-term survival of BC patients with BM was associated with better ECOG PS, younger age, HER2-positive subtype, lower number of BM and less extended visceral metastases. Patients with these clinical features might be more eligible for extended local brain and systemic treatment.

Esteem 2 middle ear implant: our experience.

INTRODUCTION: The Esteem is a totally implantable hearing system that uses piezoelectric technology. It is indicated in case of moderate to severe stable sensorineural hearing loss with a minimum discrimination score of 60% and a middle ear which is anatomically and functionally intact. Its two components (sensor and driver) are positioned and fixed in the mastoid cavity and coupled respectively to the incus body and capitulum with cement. STUDY DESIGN: Retrospective study. SETTINGS: Tertiary referral center. MATERIALS AND METHODS: Pure-tone average (PTA) gain in the implanted ear was calculated at 1, 2, and 4 KHz, word recognition score (WRS) gain at 50 dB SPL, and average WRS (AWRS) gain at 40, 55, and 70 dB SPL. WRS was also evaluated in silence and noise. All patients were asked to fill in the abbreviated profile of hearing aid benefit (APHAB) questionnaire pre- and postoperatively as well as an Esteem questionnaire. RESULTS: Thirteen patients received implants between May 2008 and April 2010. Five minor complications occurred (1 temporary partial facial palsy, 1 secondary healing difficulty, and 3 revision surgeries for poor and deteriorating functional results and progressive gain loss after use of a heart defibrillator). Two patients (15%) suffered major complications and their implants had to be removed 4 months postoperatively because of a Staphylococcus aureus wound infection. One patient underwent reimplantation 6 months later. Mean PTA gain was 25 ± 11 dB, mean WRS gain at 50 dB SPL was 64 ± 33%, and mean AWRS gain was 40 ± 20%. WRS in silence and with a signal-noise ratio of 10, 0, and -5 dB was 91 ± 11, 85 ± 14, 71 ± 19, and 64 ± 30%, respectively. The APHAB questionnaire revealed 84% of satisfaction improvement compared to the previous classic hearing aid. CONCLUSION: The totally implantable hearing device Esteem 2 can offer good functional and satisfaction results. Careful selection of patients is required, however, based on hearing tests, exclusion of middle ear ventilation problems, and CAT-scan middle ear anatomy. Specific surgical training and experience are also needed. The implant is safe and only associated with classic auditory implant complications.

Diagnosis and treatment options of vulvar cancer: a review.

INTRODUCTION: Vulvar cancer is a rare malignancy in women. However, within the past decade, a distinct increase in the incidence of vulvar intraepithelial neoplasia (VIN) as a precursor lesion, and an increase of vulvar cancer have been reported within Europe and the USA. Surgery is the first choice in treating patients with vulvar cancer, especially in its early stages. In an attempt to decrease the incidence of complications, research was made into modifications of the surgical procedure without compromising the prognosis. The replacement of radical vulvectomy by less wide local excision is one of these modifications. As vulvar cancer is relatively rare, it is possible to give evidence-based treatment recommendations, but usually on a low evidence level. Aim of this paper is to elucidate diagnostics and surgical treatment options in the management of vulvar cancer. MATERIALS AND METHODS: We searched major databases (i.e. pubmed) with the following selection criteria: vulvar cancer, en bloc resection, triple incision, and sentinel node biopsy. CONCLUSIONS: Today, the operative therapy is much less radical and more emphasized on individualized therapeutic concepts. The tendency is to leave the ultraradical surgical options which suffer from high morbidity towards less radical, minimal invasive techniques. Due to the rarity of the disease further studies will have to be performed by international collaborative groups.

Leiomyosarcoma of the vulva.

Malignant tumors of the vulva soft tissue are uncommon. About 1-3% are sarcomas. They can be mistaken as benign lesions, leading to misdiagnosis and mistreatment. A case of a 71-year-old woman with a leiomyosarcoma of the vulva is presented. The surgical excision of the lesion is described and there were no additional malignancies or lesions found. There was no need for adjuvant therapy.

[Somatic tinnitus (review). A consequence of plasticity and bimodal integration in the dorsal cochlear nucleus]. / Les somatoacouphènes (revue) : une conséquence de la plasticité et de l'int gration bimodale dans le noyau cochléaire dorsal.

Somatic tinnitus is a peculiar tinnitus type that can be defined as a tinnitus that can be modulated in intensity and/or pitch by manipulating some regions of the head and neck but also as tinnitus associated with facial pain or dysesthesis in the same area. Those areas are innervated by the trigeminal nerve and the cervical plexus. This can be explained by functional connections between the trigeminal system and the auditory brainstem and mid-brain. A literature overview shows how different messages coming from the head and neck are able to modulate the hearing information. Tinnitus is generated by an increase of the spontaneous discharges of the dorsal cochlear nucleus neurons, tonotopic reorganisation and an increase of the neural synchronism in the auditory cortex. Trigeminal stimulations have an influence on the activity of the dorsal cochlear nucleus especially in case of an associated hearing loss.

Characteristics of patients with brain metastases from human epidermal growth factor receptor 2-positive breast cancer: subanalysis of Brain Metastases in Breast Cancer Registry.

BACKGROUND: Up to 40% of patients with metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer develop brain metastases (BMs). Understanding of clinical features of these patients with HER2-positive breast cancer and BMs is vital. PATIENTS AND METHODS: A total of 2948 patients from the Brain Metastases in Breast Cancer registry were available for this analysis, of whom 1311 had primary tumors with the HER2-positive subtype. RESULTS: Patients with HER2-positive breast cancer and BMs were-when compared with HER2-negative patients-slightly younger at the time of breast cancer and BM diagnosis, had a higher pathologic complete response rate after neoadjuvant chemotherapy and a higher tumor grade. Furthermore, extracranial metastases at the time of BM diagnosis were less common in HER2-positive patients, when compared with HER2-negative patients. HER2-positive patients had more often BMs in the posterior fossa, but less commonly leptomeningeal metastases. The median overall survival (OS) in all HER2-positive patients was 13.2 months (95% confidence interval 11.4-14.4). The following factors were associated with shorter OS (multivariate analysis): older age at BM diagnosis [≥60 versus <60 years: hazard ratio (HR) 1.63, P < 0.001], lower Eastern Cooperative Oncology Group status (2-4 versus 0-1: HR 1.59, P < 0.001), higher number of BMs (2-3 versus 1: HR 1.30, P = 0.082; ≥4 versus 1: HR 1.51, P = 0.004; global P = 0.015), BMs in the fossa anterior (HR 1.71, P < 0.001), leptomeningeal metastases (HR 1.63, P = 0.012), symptomatic BMs at diagnosis (HR 1.35, P = 0.033) and extracranial metastases at diagnosis of BMs (HR 1.43, P = 0.020). The application of targeted therapy after the BM diagnosis (HR 0.62, P < 0.001) was associated with longer OS. HER2-positive/hormone receptor-positive patients showed longer OS than HER2-positive/hormone receptor-negative patients (median 14.3 versus 10.9 months; HR 0.86, P = 0.03), but no differences in progression-free survival were seen between both groups. CONCLUSIONS: We identified factors associated with the prognosis of HER2-positive patients with BMs. Further research is needed to understand the factors determining the longer survival of HER2-positive/hormone receptor-positive patients.

A multicentre, randomised, double-blind, phase II study to evaluate the tolerability of an induction dose escalation of everolimus in patients with metastatic breast cancer (DESIREE).

BACKGROUND: Stomatitis is one of the main reasons to discontinue everolimus in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC). To decrease stomatitis and subsequently early treatment discontinuations or dose reductions, the DESIREE trial investigated the use of a stepwise dose-escalation schedule of everolimus (EVE esc). PATIENTS AND METHODS: DESIREE is a phase II, multicentre, randomised, double-blind, placebo-controlled trial in patients with HR+/HER2- mBC and progression/relapse after nonsteroidal aromatase inhibitor treatment. Patients were randomised to EVE esc (2.5 mg/day, week 1; 5 mg/day, week 2; 7.5 mg/day, week 3; 10 mg/day, weeks 4-24) or everolimus 10 mg/day (EVE 10mg) for 24 weeks plus exemestane. The primary endpoint was the incidence of stomatitis episodes grade ≥2 within 12 weeks of treatment. The secondary endpoints included toxicity, relative total dose intensity (RTDI) and quality of life (QoL). RESULTS: A total of 160 patients were randomised and 156 started treatment (EVE esc: 80; EVE 10mg: 76). The median age of patients was 64 years (range 33-85), 56.3% patients in the EVE esc arm versus 42.1% in the EVE 10mg arm had liver metastasis (P = 0.081) and 62.5% versus 51.3% received over one metastatic therapy line (P = 0.196). Within 12 weeks, the incidence of stomatitis episodes grade ≥2 was significantly lower in the EVE esc arm compared with the EVE 10mg arm (28.8% versus 46.1%; odds ratio 0.47, 95% confidence interval 0.24-0.92; P = 0.026). Toxicity was in line with the known safety profile without new safety concerns. The median RTDI was 91.1% in the EVE esc arm versus 80.0% in the EVE 10mg arm (P = 0.329). Discontinuation rate in the first 3 weeks was 6.3% versus 15.8%, respectively (P = 0.073). QoL was comparable between the two treatment arms. CONCLUSIONS: A dose-escalation schema of everolimus over 3 weeks can be successfully used to reduce the incidence of high-grade stomatitis in the first 12 weeks of treatment in patients with HR+/HER2- mBC. TRIAL REGISTRATION: ClinicalTrials.govNCT02387099; https://clinicaltrials.gov/ct2/show/NCT02387099.

Epidemiology of vulvar and vaginal cancer in Germany.

OBJECTIVE: Vulvar and vaginal cancers are rare diseases with an incidence rate that increases with age. At present, epidemiological data are rather scarce. This review article provides an epidemiologic overview of these diseases, focussing on recent German data. METHODS: This review article summarizes the information currently available in order to offer an epidemiologic overview. RESULTS: The statistic incidence of vulvar carcinoma has been calculated between 2 and 7 cases per 100,000 women, and that of vaginal carcinoma 0.6-1.0 cases per 100,000 women. These incidence rates, especially concerning intraepithelial neoplasm, have increased heavily since the 1970s. The mean age of vulvar cancer affection is 72 years, and 74 years for vaginal carcinoma. In the case of women below the age of 50, cancer tends to be HPV-associated which implies a coincidence of about 20% for cervical and anal cancer. Various pathological mechanisms are the cause for women above the age of 50. CONCLUSIONS: Due to a change in sexual behavior and an increased rate of HPV infection among younger women, increased incidence of both diseases has to be expected. The age-standardized mortality rate of vulvar carcinoma in Europe is stated at 0.7/100,000 women, and that of vaginal carcinoma at 0.4/100.000 women. To what extent the HPV-vaccination affects incidence and mortality rates is continually being observed.

Compliance to adjuvant therapy in breast cancer patients.

During recent years a continuous reduction of mortality from breast cancer has taken place in the Western countries. We wanted to verify whether the actual therapy for our own cases deviates from our recommendations, although the surgeon, radiotherapist and gynaecological oncologist are on the same premises. We sent out questionnaires to all newly diagnosed breast cancer patients in the last seven years regarding their adjuvant therapy. Comparing these answers to our own recommendation showed a very good compliance regarding chemotherapy and radiation therapy. Adjuvant endocrine therapy showed a very poor compliance with an adherence of 77%. Overall we can conclude that endocrine therapy causes many side-effects that seem to burden the patients. In combination with the duration of the therapy this causes a severe reduction in compliance and length of the therapy.

Immunhistochemical analysis for expression of calpain 1, calpain 2 and calpastatin in ovarian cancer.

Calpains, also called calcium activated neutral proteases (CANP), are expressed ubiquitously. They are intracellular, non-lysosomal cytoplasmic cysteine endopeptidases. Calcium is required for their activation. Their endogenous specific inhibitor is calpastatin, which is expressed ubiquitously and coexists within cells besides calpain. When calcium is present, calpastatin and calpain attach to each other inhibiting the protease. The calpain system plays an important role in many processes including apoptosis, necrosis, ischemia formation and exocytosis. So far, many reports exist on studies about the influence of calpains in different tumors (skin, breast, renal cell and prostate cancers). The role of calpains in pathogenesis or further tumor progression has always been proved in related studies, but their exact function could not be demonstrated. So far, no studies on calpains being involved in the pathogenesis of ovarian cancer have been published. In our study we focused on the expression of the enzymes calpain 1, calpain 2 and their inhibitor calpastatin in normal and malign ovarian tissue. Therefore, we performed immunohistochemical stainings of paraffin slices and evaluated staining intensity (SI), percentage of positive cells (PP) and immunoreactive score (IRS). We evaluated the correlation between enzyme expression in malign and benign ovarian tissues. In malignant ovarian tissue, we found decreased expression, staining intensity and immunoreactive score of calpastatin. With higher grading of the ovarian carcinoma, staining intensity and immunoreactive score of calpain 1 decreased. Staining intensity of calpain 2 in ovarian carcinoma decreased with increasing lymph node status. We clearly demonstrated differences between enzyme expressions in malign and benign tissue. This study could not find any specific function of calpains. Only few studies in the literature have been found that deal with calpain evaluation of ovarian cancer. Additional studies including more patients are required to elucidate the functional role and impact of calpain in tumors in detail.

Successful laser therapy of a papular acantholytic dyskeratosis of the vulva: case report and review of literature.

BACKGROUND: The papular acantholytic dyskeratosis summarizes a collection of papular skin lesions which occur in intertriginous areas and in the genital area. They show a very characteristic histology without the connection to a syndrome such as the Hailey-Hailey disease or the Darier disease. METHODS: We present the case of an affected 45-year-old woman and evaluate the laser therapy as therapeutic option. RESULTS: A long lasting reduction of the symptoms was achieved by paying special attention to involving the deep tissue layers while performing the laser therapy. Despite causing a long and painful healing process, this was the only way to achieve a lasting reduction of the symptoms. CONCLUSIONS: Laser therapy in afflicted areas can improve the symptoms of the papular acantholytic dyskeratosis. The deep tissue laser therapy showed more success than the superficial laser therapy.