Comparison of cheeses from goats fed 7 forages based on a new health index.

This study proposed the General Health Index of Cheese (GHIC) as an indicator for the presence of health-promoting compounds in cheese and compared the antioxidant capacity and phenolic and fatty acid contents of cheeses from goats consuming 7 forage species. Ninety-one homogeneous Red Syrian goats were randomly assigned to 1 of 7 feeding treatments (Festuca arundinacea, Hordeum vulgare, Triticosecale, Pisum sativum, Trifolium alexandrinum, Vicia sativa, and Vicia faba minor). The housed goat groups received the scheduled forage ad libitum. Forage species affected the antioxidant capacity, the phenolic and fatty acid contents, the Health Promoting Index, and the GHIC. Trifolium alexandrinum, Triticosecale, and Hordeum vulgare showed a clear advantage in terms of beneficial fatty acids content in goat cheese. Cheese from the Triticosecale group also showed a high antioxidant capacity value even if its polyphenol content was intermediate compared with others. Trifolium alexandrinum and Triticosecale had the highest value of the new index GHIC. This comparison suggests that there are important differences in fatty acid profile and polyphenol content among cheeses from goats fed grasses and legumes commonly used in the Mediterranean area. In this first approach, GHIC index, which combines the positive components found in cheese, seems to be a useful tool to provide an indication concerning the general health value of the product.

Trabectedin in Ovarian Cancer: is it now a Standard of Care?

In patients with recurrent ovarian cancer, the choice of second-line therapy is complex. Several factors have to be considered, such as platinum-free interval (PFI), residual toxicity from the previous treatments, BRCA1/2 gene mutation status. Trebectedin is a minor groove DNA binder derived from a marine organism that has shown efficacy in different settings in ovarian cancer therapy. It has been approved in the treatment of partially platinum sensitive (PPS) (PFI between 6 and 12 months) relapsed ovarian cancer according to the statistically significant progression-free survival (7.3 versus 5.8 months) and overall survival (22.2 versus 18.9 months) benefit compared with single-agent pegylated liposomal doxorubicin (PLD) in the OVA 301 phase III trial. This drug has been shown to prolong the time to first subsequent treatment and improve the efficacy of further platinum-based chemotherapy. The role of trabectedin/PLD followed by platinum combination compared with the reverse sequence in PPS is actually in evaluation in the INOVATYON phase III study, which will clarify the best sequence to be adopted in this setting. Trabectedin has been shown to be active in patient carriers of BRCA mutations, probably for its mechanism of action directly affecting DNA and it is actually tested as a single agent in some phase III trials in BRCA mutated and BRCAness ovarian cancer patients. Trabectedin is also active on the immune system. There is, therefore, the rational for new trials of a combination with immune checkpoint inhibitors.

Quality-of-life analysis of the MITO-8, MaNGO, BGOG-Ov1, AGO-Ovar2.16, ENGOT-Ov1, GCIG study comparing platinum-based versus non-platinum-based chemotherapy in patients with partially platinum-sensitive recurrent ovarian cancer.

Background: MITO-8 showed that prolonging platinum-free interval by introducing non-platinum-based chemotherapy (NPBC) does not improve prognosis of patients with partially platinum-sensitive recurrent ovarian cancer. Quality of life (QoL) was a secondary outcome. Patients and methods: Ovarian cancer patients recurring or progressing 6-12 months after previous platinum-based chemotherapy (PBC) were randomized to receive PBC or NPBC as first treatment. QoL was assessed at baseline, third and sixth cycles, with the EORTC C-30 and OV-28 questionnaires. Mean changes and best response were analysed. Progression-free survival, response rate, and toxicity are also reported for proper interpretation of data. All analyses were based on intention-to-treat. Results: Out of the 215 patients, 151 (70.2%) completed baseline questionnaire, balanced between the arms; thereafter, missing rate was higher in the NPBC arm. At mean change analysis, C30 scores were prevalently worse in the NPBC than PBC arm, statistical significance being attained for emotional functioning, global health status/QoL, fatigue, and dyspnoea (effect sizes ranging from 0.30 to 0.51). Conversely, as for OV28 scale, the other chemotherapy side-effects item was significantly worse with PBC at three and six cycles, with a larger effect size (0.70 and 0.54, respectively). At best response analysis, improvement of emotional functioning and pain and worsening of peripheral neuropathy and other chemotherapy side-effects were significantly more frequent in the PBC arm. Progression-free survival (median 9 versus 5 months, P = 0.001) and objective response rate (51.6% versus 19.4%, P = 0.0001) were significantly better with PBC. Allergy, blood cell count, alopecia, nausea, musculoskeletal, and neurological side-effects were more frequent and severe with PBC; hand-foot skin reaction, rash/desquamation, mucositis, and vascular events were more frequent with NPBC. Conclusion: MITO-8 QoL analysis shows that deterioration of some functioning and symptom scales is lower with PBC, with improvement of emotional functioning and pain, despite worsening of toxicity-related items. ClinicalTrials.gov: NCT00657878.

Cisplatin can be safely administered to ovarian cancer patients with hypersensitivity to carboplatin.

OBJECTIVE: Hypersensitivity reactions (HSR) are frequently reported in patients rechallenged with carboplatin for recurrent ovarian cancer (ROC) and represent a critical issue, since discontinuation of the platinum-based therapy could affect prognosis. Several strategies to allow platinum rechallenge have been described, with controversial outcomes. The aim of this study is to illustrate a 10-year experience with cisplatin in patients with a previous HSR to carboplatin or at risk for allergy. METHODS: A retrospective review of all patients with platinum sensitive ROC retreated with carboplatin was performed between January 2007 and May 2016 at the Istituto Nazionale Tumori, Fondazione "G. Pascale", Naples. RESULTS: Among 183 patients, 49 (26.8%) presented HSR to carboplatin, mainly during second line therapy. Mean number of cycles before HSR was 8 (range 3-17). G2, G3 and G4 reaction were detected in 83%, 15% and 2% of patients, respectively. In a multivariate analysis including age, hystotype, BRCA status, previous known HSR, and combination drug administered, only the type of carboplatin-based doublet used as 2nd line therapy was found to significantly affect HSR development, with a protective effect of PLD (pegylated liposomal doxorubicin) (p = 0.014, OR = 0.027). Thirty seven patients (77%) with a previous HSR to carboplatin were rechallenged with cisplatin. Treatment was generally well tolerated. 5 patients (13.1%) experienced mild HSR to cisplatin, successfully managed in all cases. 14 patients were treated with cisplatin even without a carboplatin-related HSR due to other allergies. Among these, only one developed HSR (7.1%). CONCLUSIONS: Cisplatin rechallenge is a feasible approach in patients experiencing HSR to carboplatin to maintain the beneficial effect of platinum while reducing hypersensitivity-related risks.

Prospective phase II trial of trabectedin in BRCA-mutated and/or BRCAness phenotype recurrent ovarian cancer patients: the MITO 15 trial.

BACKGROUND: Current evidence suggest that trabectedin is particularly effective in cells lacking functional homologous recombination repair mechanisms. A prospective phase II trial was designed to evaluate the activity of trabectedin in the treatment of recurrent ovarian cancer patients presenting BRCA mutation and/or BRCAness phenotype. PATIENTS AND METHODS: A total of 100 patients with recurrent BRCA-mutated ovarian cancer and/or BRCAness phenotype (≥2 previous responses to platinum) were treated with trabectedin 1.3 mg/mq i.v. q 3 weeks. The activity of the drug with respect to BRCA mutational status and to a series of polymorphisms [single-nucleotide polymorphisms (SNPs)] involved in DNA gene repair was analyzed. RESULTS: Ninety-four were evaluable for response; in the whole population, 4 complete and 33 partial responses were registered for an overall response rate (ORR) of 39.4. In the platinum-resistant (PR) and -sensitive (PS) population, an ORR of 31.2% and 47.8%, and an overall clinical benefit of 54.2% and 73.9%, respectively, were registered. In the whole series, the median progression-free survival (PFS) was 18 weeks and the median overall survival (OS) was 72 weeks; PS patients showed a more favorable PFS and OS compared with PR patients. BRCA gene mutational status was available in 69 patients. There was no difference in ORR, PFS and OS according to BRCA 1-2 status nor any association between SNPs of genes involved in DNA repair and NER machinery and response to trabectedin was reported. CONCLUSIONS: Our data prospectively confirmed that the signature of 'repeated platinum sensitivity' identifies patients highly responsive to trabectedin. In this setting, the activity of trabectedin seems comparable to what could be obtained using platinum compounds and the drug may represent a valuable alternative option in patients who present contraindication to receive platinum. EUDRACT NUMBER: 2011-001298-17.

Intravesical chemo-immunotherapy in non muscle invasive bladder cancer.

Non-Muscle-Invasive-Bladder-Cancer represents 75-85% of the new bladder cancer cases per year. Trans-uretral vesical resection is the milestone for diagnosis and therapy. After primary treatment, recurrence is frequent depending on the presence of several established risk factors: multiplicity, T dimension, prior recurrence. In some patients disease progress to an advanced stage. Adjuvant chemo-immunotherapy has been widely used depending on the risk category assigned on the basis of the risk factors for recurrence. In low risk categories a one shot treatment with chemotherapy is considered the standard treatment without any maintenance therapy. In intermediate risk patients, adjuvant induction therapy and maintenance chemotherapy or immunotherapy for at least one year is recommended. In high risk patients adjuvant induction and maintenance immunotherapy until 3 years is considered the best strategy. In this review data on the different drugs used in this setting will be discussed.

Multidisciplinary treatment of early stage endometrial cancer.

Endometrial cancer is a highly curable malignancy when it presents as uterine-confined disease, but the prognosis for metastatic or recurrent endometrial cancer is poor. For those patients which are diagnosed at an early stage, surgery alone may be adequate for cure and clinical outcome is often favorable, with approximately 80 % of cases surviving at 5 years. However, after primary diagnosis and treatment, roughly 20-30% of patients are expected to recur within the following 5 years. Adjuvant treatment for endometrial cancer is not yet clearly defined. FIGO Stage I-III endometrial cancer patients, usually undergo surgery and some of them are offered adjuvant treatment based on risk assessment. Grade, age, stage are considered all independent risk factors for recurrence. Radiotherapy (RT) has been considered the adjuvant treatment of choice for decades, being able to reduce local recurrence rate and improving progression free survival, but without any impact on overall survival. In the last two decades, a shift toward the use of systemic chemotherapy (CT) in addition or instead of radiation has occurred, although few prospective studies have been performed in this field.

[The euthyroid sick syndrome. Its incidence and clinical significance in an internal medicine department]. / Sindrome del malato eutiroideo. Incidenza e significato clinico in un reparto di medicina interna.

In this paper the authors have evaluated the incidence and the clinical implications of sick euthyroid syndrome (SES) in a group of 144 patients in a department of internal medicine. SES is an alteration of thyroid hormone values in the absence of a thyroid disease, which is seen in patients suffering from serious diseases. Having classified SES into 3 subgroups according to the different alterations seen in the values of T3, T4, FT3, FT4, TSH, rT3 and TBG, they show the hypotheses that explain the biochemical mechanisms which are at the basis of these hormonal alterations. Fourteen of the 144 patients under observation were excluded as they were suffering from ascertained or subclinical thyroid disease. Thirty (23% of cases) of the remaining 130 patients had alterations of the thyroid hormones in accordance with SES diagnosis. Of these 30 patients, 19 had hormone values found in SES type I (63%), 2 in SES type II (6.5%) and 9 in SES type III (30.5%). In SES type I the diseases seen, in order of frequency, were: obstructive chronic bronchopneumopathy with acute respiratory failure, diabetic ketoacidosis, neoplasms, ischemic heart disease, cardiac failure, chronic renal failure, liver diseases, acute cerebral vasculopathies, sepsis and collagenopathies. The disease seen in the 2 cases of SES type II was obstructive chronic bronchopneumopathy with acute respiratory failure. In SES type III the diseases seen were, in order of frequency: diabetic ketoacidosis, lung diseases, ischemic heart disease, cardiac failure, peripheral arteriopathies, acute cerebral vasculopathies, neoplasms, liver diseases, acute renal failure. The incidence of SES in 23% of the admitted to hospital patients was found to be slightly higher than in other studies; this could be explained by a stricter selection of inpatients: in fact self-sufficient patients or those not needing urgent admission, were sent to an efficient out patient clinic where necessary examinations were quickly carried out, hospitalization being reserved for patients with more serious illnesses. We would like to underline how the incidence of SES is much greater than that of what is known as thyroid disease (23% compared to 5%), thereby confirming that it is the most frequent cause of alterations of thyroid hormones. With regard to the pathogenetical hypotheses, it is confirmed that in SES, the reduction of T3 values is accompanied by an increase in the values of rT3 as for reduced activity of 5-desiodinasis enzyme. In SES type III the increase of T4 values is due to the increase of TBG resulting in an increase in the link for T4 and therefore a reduced peripheral hormone activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Colchicina no tratamento de esclerodermia regional. / Colchicine in the treatment of regional scleroderma

A colchicina tem sido indicada no tratamento de esclerodermia por sua atuacao sobre a colagenase e os microtubulos do reticulo endosplamatico do fibroblasto, impedindo a extrusao de fibras colagenas. Os autores apresentam os resultados obtidos com o uso da colchicina (1,5 e 3mg/dia) em cinco pacientes acometidos por esclerodermia facial (morfeia difusa I, esclerose multifocal 3, forma em "golpe de sabre" I) Os pacientes, todos dos sexo feminino e cor branca, grupo etario assim constituido 9, 11, 12, 25, 35 anos, foram acompanhados durante doze meses.Tendo em conta dificuldade na interpretacao a inutilidade dos parametros laboratorias na esclerodermia focal, os criterios de avaliacao levados em conta constituiram-se em area de superficie corporal acometida, grau de aderencia da pele aos planos profundos, evolucao das areas de hipercromia e biopsia da pele Os resultados demosntraram atenuacao consistente da extensao da area corporal acometida (30-40%), elasticidade da pele (50-60%), da hipercromia e regressa do halo de infiltracao com diminuicao da zona de aderencia central