European experts consensus: BRCA/homologous recombination deficiency testing in first-line ovarian cancer

Background: Homologous recombination repair (HRR) enables fault-free repair of double-stranded DNA breaks. HRR deficiency is predicted to occur in around half of high-grade serous ovarian carcinomas. Ovarian cancers harbouring HRR deficiency typically exhibit sensitivity to poly-ADP ribose polymerase inhibitors (PARPi). Current guidelines recommend a range of approaches for genetic testing to identify predictors of sensitivity to PARPi in ovarian cancer and to identify genetic predisposition. Design: To establish a European-wide consensus for genetic testing (including the genetic care pathway), decision making and clinical management of patients with recently diagnosed advanced ovarian cancer, and the validity of biomarkers to predict the effectiveness of PARPi in the first-line setting. The collaborative European experts’ consensus group consisted of a steering committee (n = 14) and contributors (n = 84). A (modified) Delphi process was used to establish consensus statements based on a systematic literature search, conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Results: A consensus was reached on 34 statements amongst 98 caregivers (including oncologists, pathologists, clinical geneticists, genetic researchers, and patient advocates). The statements concentrated on (i) the value of testing for BRCA1/2 mutations and HRR deficiency testing, including when and whom to test; (ii) the importance of developing new and better HRR deficiency tests; (iii) the importance of germline non-BRCA HRR and mismatch repair gene mutations for predicting familial risk, but not for predicting sensitivity to PARPi, in the first-line setting; (iv) who should be able to inform patients about genetic testing, and what training and education should these caregivers receive. Conclusion: These consensus recommendations, from a multidisciplinary panel of experts from across Europe, provide clear guidance on the use of BRCA and HRR deficiency testing for recently diagnosed patients with advanced ovarian cancer

Treatment of patients with metastatic renal cell carcinoma undergoing hemodialysis: Case report of two patients and short literature review

Background: Renal cell carcinoma (RCC) may involve both kidneys. When bilateral nephrectomy is necessary renal replacement therapy is mandatory. Treating such patients with sequential therapy based on cytokines, antiangiogenic factors and mammalian target of rapamycin (mTOR) inhibitors is challenging. Case presentation. The first case, a 50-year-old Caucasian female, underwent a radical right nephrectomy for RCC. Twelve years later she underwent a radical left nephrectomy along with total hysterectomy including bilateral salpingo-oophorectomy for RCC involving the right kidney and ovary. Hemodialysis was necessary because of bilateral nephrectomy. She relapsed with pulmonary metastases and enlarged mediastinal lymph nodes and received cytokine based therapy along with bevacizumab. Therapy was discontinued despite the partial response because of hemorrhagic gastritis. Therapy was switched to an antiangiogenic factor but the patient manifested a parietal brain hematoma and stopped therapy. Subsequently disease relapsed with malignant pleural effusion and pulmonary nodules and a mammalian target of rapamycin inhibitor was administered which was withdrawn only at patient's deteriorating performance status. The patient died of the disease 13 years after the initial diagnosis of RCC.The second case, a 51-year-old, Caucasian male, underwent a radical right nephrectomy for a chromophobe RCC. Six months later he underwent a radical left nephrectomy for RCC that proved to be a clear cell RCC. Due to bilateral nephrectomy hemodialysis was obligatory. Following disease recurrence at the anatomical bed of the right kidney therapy with antiangiogenic factor was administered which led to disease regression. However the patient experienced a left temporal-occipital brain hematoma. A radical excision of the recurrence which histologically proved to be a chromophobe RCC was not achieved and the patient received mTOR inhibitor which led to disease complete response. Nine years after the initial diagnosis of RCC he is disease free and leads an active life. Conclusion: Patients with RCC are in significant risk to manifest bilateral disease. Renal insufficiency requiring hemodialysis poses therapeutic challenges. Clinicians must be aware of the antiangiogenic factors' adverse effects, especially bleeding, that may manifest in higher frequency and more severe in this setting. © 2013 Syrios et al.; licensee BioMed Central Ltd

A comparison of reverse osmosis, nanofiltration and ultrafiltration as concentration processes for skim milk prior to drying

Skim milk was concentrated by reverse osmosis (RO), nanofiltration (NF) and ultrafiltration (UF) and the retentates were spray-dried. The resulting powders were reconstituted to 25% TS and sterilised to evaluate their heat stability. Reverse osmosis led to maximum retention of calcium, a fall in pH for its retentate and its reconstituted powder. All RO powders produced a weak gel on heating. Some calcium was lost during NF and a greater amount during UF. Their resulting reconstituted powders had a higher pH than those produced by RO. Powders produced by UF showed poor heat stability. Only one powder produced by NF showed good heat stability. This could be improved by addition of stabilisers at appropriate addition rates

An ovarian mature cystic teratoma evolving in squamous cell carcinoma: A case report and review of the literature

Mature cystic teratomas (MCT), also known as dermoid cysts, are the most common ovarian germ cell tumors and the most common ovarian neoplasms in patients younger than 20 years. Malignant transformation (MT) is a rare complication of MCTs which may occur in 1–2% of the cases. Squamous cell carcinoma (SCC) is the most frequent histology arising from MCTs and its appearance depends on diverse risk factors such as patient's age, the size of the tumor and levels of serum tumor markers. Diagnosis and treatment constitute a big challenge due to the rarity and the aggressive course of this entity. Adjuvant chemotherapy has a leading role in the treatment of MCT-arising SCC, while the use of radiotherapy or chemoradiation is still under consideration. Herein, we report a case of a post-menopausal woman, presenting with mild symptoms and a large pelvic mass deriving from the left ovary occurring as dermoid cyst. Simultaneously, we review the literature stressing out the prognostic factors and the treatment options for MCT arising SCC according to traditional and new therapy-strategies

Pancreatic adenocarcinoma-associated polymyositis treated with corticosteroids along with cancer specific treatment: Case report

Background: Adenocarcinoma of the pancreas only rarely is associated with inflammatory myopathy. In this setting, polymyositis may be treated with glucocorticoids in combination with cancer specific treatment.Case presentation: We present the case of a 52-year-old man with stage IIA pancreatic tail adenocarcinoma who underwent surgical treatment and six months into therapy with gemcitabine he developed symmetrical, painful, proximal muscle weakness with peripheral oedema. Re-evaluation with imaging modalities, muscle histology and biochemistry conferred the diagnosis of polymyositis associated with pancreatic cancer progression. The patient was treated with glucocorticoids along with gemcitabine and erlotinib which resulted in complete remission within six months. He remained in good health for a further six months on erlotinib maintenance therapy when a new computer tomography scan showed pancreatic cancer relapse and hence prompted 2ndline chemotherapy with gemcitabine.Conclusions: Polymyositis associated with pancreatic cancer may respond to glucocorticoids along with cancer specific treatment. © 2011 Syrios et al; licensee BioMed Central Ltd

Palliative gastrectomy and other factors affecting overall survival in stage IV gastric adenocarcinoma patients receiving chemotherapy: A retrospective analysis

Objective: Most patients with gastric cancer present with locally advanced or metastatic disease and usually receive palliative therapy. We sought to identify factors influencing overall survival in patients with stage IV gastric cancer receiving palliative chemotherapy. Patients and methods: The records of 311 patients with histological diagnosis of gastric adenocarcinoma were retrospectively reviewed and 17 clinicopathological and therapeutic parameters were evaluated for their influence on overall survival. Results: In multivariate analysis nine factors were found to independently influence survival: no previous palliative gastrectomy [Hazard ratio (HR, 12; CI 7.969-18.099)], single agent chemotherapy instead of combination chemotherapy (HR, 1.35; CI 1.068-1.721), histological grade III (HR, 1.39; 95% CI 1.098-1.782), the presence of hepatic (HR, 1.6; 95% CI 1.246-2.073) and abdominal metastasis (HR, 1.33; 95% CI 1.039-1.715), CA 72-4 > 7 U/L (HR, 1.39; 95% CI 1.026-1.887), LDH > 225 U/L (HR, 1.72; 95% CI 1.336-2.236], need for blood transfusions (HR, 1.58; 95% CI 1.213-2.082), and weight loss > 5% (HR, 1.96; 95% CI 1.352-2.853) at the time of initial diagnosis. Patients were stratified as low (0-2 factors), intermediate (3-6 factors) and high (7-9 factors) risk and the median survival was 76, 40 and 11 weeks, respectively. Conclusion: Nine clinical and laboratory factors that adversely affect survival in patients with stage IV gastric cancer who receive chemotherapy were identified. Their concurrent presence seems to have an additive effect as patients with seven to nine factors have the worse prognosis. Palliative gastrectomy and combination chemotherapy appear to be associated with improved survival. © 2010 Elsevier B.V. All rights reserved