Vulvar cancer: epidemiology, clinical presentation, and management options.

EPIDEMIOLOGY: Vulvar cancer can be classified into two groups according to predisposing factors: the first type correlates with a HPV infection and occurs mostly in younger patients. The second group is not HPV associated and occurs often in elderly women without neoplastic epithelial disorders. HISTOLOGY: Squamous cell carcinoma (SCC) is the most common malignant tumor of the vulva (95%). CLINICAL FEATURES: Pruritus is the most common and long-lasting reported symptom of vulvar cancer, followed by vulvar bleeding, discharge, dysuria, and pain. THERAPY: The gold standard for even a small invasive carcinoma of the vulva was historically radical vulvectomy with removal of the tumor with a wide margin followed by an en bloc resection of the inguinal and often the pelvic lymph nodes. Currently, a more individualized and less radical treatment is suggested: a radical wide local excision is possible in the case of localized lesions (T1). A sentinel lymph node (SLN) biopsy may be performed to reduce wound complications and lymphedema. PROGNOSIS: The survival of patients with vulvar cancer is good when convenient therapy is arranged quickly after initial diagnosis. Inguinal and/or femoral node involvement is the most significant prognostic factor for survival.

Application of ex vivo micro-computed tomography for assessment of in vivo fluorescence and plain radiographic imaging for monitoring bone metastases and osteolytic lesions.

The intracardiac injection model is a commonly used in vivo model to test therapeutic response in bone metastases. However, few studies have critically compared the performance of different imaging methods in terms of sensitivity and quantitative assessment of osteolytic lesions. We performed in vivo optical and plain radiographic imaging of bone metastases followed by high-sensitivity ex vivo micro-computed tomography (micro-CT) imaging. This approach allowed for quantitative assessment of in vivo imaging techniques using fluorescence and plain radiography. Comparison of lesions detected in vivo by fluorescent optical imaging with ex vivo micro-CT revealed that the limited spatial resolution of fluorescent optical imaging may underestimate the number of bone metastases. Radiography was compared with micro-CT for the detection of osteolytic lesions. When using dichotomous yes/no grading, there was a 64% agreement in detection of osteolytic lesions. When subjective semiquantitative grading methods were used to assess the extent of osteolytic lesions, a positive association between the micro-CT grades and the square root of the radiography-based grades was observed (p < 0.05). Micro-CT also showed a significant association with fluorescent optical values; however, no such association was observed between lesion scores based on radiographs and those based on fluorescent imaging. The findings reveal an approximate two-fold sensitivity for micro-CT compared to plain radiography in the detection of osteolytic lesions. Significant associations between micro-CT-based osteolytic lesion grade and tumor growth characterized by increased fluorescent area document the value of these two techniques for the assessment of osteolytic bone metastases.

Results of the Zometa cost-utility model for the german healthcare system based on the results of the ABCSG-12 study.

BACKGROUND: The ABCSG-12 trial investigated the efficacy of gonadotropin-releasing hormone (GnRH)analogs in combination with tamoxifen or anastrozole + or - zoledronic acid (4 mg, q6m for 3 years) in 1,803 premenopausal women with hormone receptor-positive (HR+) breast cancer. After 48 months of follow-up, there was a 36% improvement in the disease-free survival (DFS) (recurrence-free survival 35%) using zoledronic acid. Based on these data, the costutility of zoledronic acid was calculated for the German healthcare system. MATERIALS AND METHODS: Costs of surveillance, adverse effects, recurrence, contralateral breast cancer, metastasis, and end-of-life care were determined based on the Einheitlicher Bewertungsmabetastab (EBM 2009) and the diagnosis-related groups (DRG) system. Utilities were surveyed with a questionnaire (n = 95). Estimation of the cost-utility was made by calculating the incremental costeffectiveness ratio (ICER) per quality-adjusted life year (QALY), using a Markov model. RESULTS: Including zoledronic acid as adjuvant therapy for 3 years resulted in total costs of euro 2,262. The use of zoledronic acid is dominant when clinical efficacy and quality of life are taken into consideration (- euro 45.83/QALY) (95% confidence interval (CI) - euro 1,838 to E 2,375; 0.02-0.41 QALY). The sensitivity analyses present with a probability of 90% that the cost per QALY gained are

Cost-effectiveness analysis of anastrozole versus tamoxifen in adjuvant therapy for early-stage breast cancer - a health-economic analysis based on the 100-month analysis of the ATAC trial and the German health system.

BACKGROUND: In the 'Arimidex', Tamoxifen Alone or in Combination (ATAC) trial, the aromatase inhibitor (AI) anastrozole had a significantly better efficacy and safety profile than tamoxifen as initial adjuvant therapy for hormone receptor-positive (HR+) early breast cancer (EBC) in postmenopausal patients. To compare the combined long-term clinical and economic benefits, we carried out a cost-effectiveness analysis (CEA) of anastrozole versus tamoxifen based on the data of the 100month analysis of the ATAC trial from the perspective of the German public health insurance. PATIENTS AND METHODS: A Markov model with a 25-year time horizon was developed using the 100-month analysis of the ATAC trial as well as data obtained from published literature and expert opinion. RESULTS: Adjuvant treatment of EBC with anastrozole achieved an additional 0.32 quality-adjusted life-years (QALYs) gained per patient compared with tamoxifen, at an additional cost of D 6819 per patient. Thus, the incremental cost effectiveness of anastrozole versus tamoxifen at 25 years was D 21,069 ($30,717) per QALY gained. CONCLUSIONS: This is the first CEA of an AI that is based on extended follow-up data, taking into account the carryover effect of anastrozole, which maintains the efficacy benefits beyond therapy completion after 5 years. Adjuvant treatment with anastrozole for postmenopausal women with HR+ EBC is a cost-effective alternative to tamoxifen.

Assessment of reliability endometrial brush cytology in detection etiology of late postmenopausal bleedings.

We evaluated the possibility of discovering bleeding causes in late postmenopausal period with cytological examination of material received by endometrial brush in comparison with Pap test and fractionated curettage. Sixty-two women in late postmenopausal period with cervical canal bleeding, treated in gynecological department of clinical hospital in Osijek, were cytological and histological processed. Final diagnosis in 29 from 62 (46.8%) women with late postmenopausal bleeding was cancer. 25 (40.3%) women had endometrial adenocarcinoma and 4 (6.5%) of them had squamous endocervical carcinoma. Two women had endometrial precancerous (3.2%). With Pap test accurate diagnosis was set up in 13 from 25 (52.0%) women with endometrial adenocarcinoma and in all of them with squamous endocervical carcinoma. With endometrial brush accurate diagnosis was set up in 14 from 25 (56.0%) women with endometrial adenocarcinoma and in 3 from 4 (75.0%) women with squamous endocervical carcinoma. With fractional curettage the diagnosis of endometrial adenocarcinoma was accurately correct in 21 from 25 (84.0%) women and in all of them with squamous endocervical carcinoma. Cytological examination of material derived with endometrial brush, alike vaginal cytology, is not enough reliable method in our conditions for discovering bleeding causes in late postmenopausal period. Diagnostic exactness of procedure could be increased by histopathological examination of material from endometrial brush procedure and with ultrasound evaluation of endometrium thickness.