Cutaneous soft tissue sarcomas: survival-related factors.

Cutaneous sarcomas are a heterogeneous group of rare mesenchymal neoplasms representing less than 1% of malignant tumors. Histology report remains the cornerstone for the diagnosis of these tumors. The most important clinicopathologic parameters related to prognosis include larger tumor size, high mitotic index, head and neck location, p53 mutations, depth of infiltration and histological grade, vascular and perineural invasion as well as the surgical margins status. Applying advanced biopsy techniques might offer more precise assessment of surgical margins, which constitutes a significant precondition for the management of these tumors. The management of cutaneous soft tissue sarcomas requires a multidisciplinary approach. Surgery remains the standard treatment, nonetheless adjuvant therapy may be required, consisting of radiotherapy, chemotherapy, and molecular targeted therapies to improve treatment outcomes. The role of molecular profiling in the treatment of uncontrolled disease is promising, but it may be offered to a relatively small proportion of patients and its use is still considered experimental in this setting. Due to the rarity of the disease, there is a need for knowledge and experience to be shared, pooled, organized and rationalized so that recent developments in medical science can have a major impact on the disease course. Multicenter clinical trials are needed to improve the care of patients with cutaneous sarcomas.

Radiation-Induced Oral Mucositis in Head and Neck Cancer Patients. Five Years Literature Review.

Backround: Radiation-induced oral mucositis consists of a series of relatively frequent side effects after head and neck cancer radiotherapy and has an adverse impact on both regular treatment process and the quality of life of patients. OBJECTIVE: The purpose of the present review is to optimize the current management of radiation-induced oral mucositis in head and neck cancer patients. METHODS: PubMed database research was performed on articles published since 2015 that demonstrated efficacy in the management of radiation-induced oral mucositis in head and neck cancer patients. The study selection included observational, prospective, comparative, randomized, double- blind, placebo-controlled or uncontrolled, and retrospective studies, as well as systematic reviews and metanalyses. RESULTS: From the 931 citations obtained from the search, only 94 articles met the inclusion criteria, including mucosal protectants, anti-inflammatory agents, growth factors, and various miscellaneous and natural agents. Several methods, including both pharmacological and natural agents, have been proposed for the management of oral mucositis. In addition to the already known interventions with strong evidence, according to the Multinational Association of Supportive Care in Cancer and he International Society of Oral Oncology guidelines, further agents have been used. However, a great number of them lack clear evidence, which surely requires the design of more controlled clinical trials for a better assessment of the ideal methods. CONCLUSION: The management of oral mucositis constitutes an active area of research. In light of these results, it is aimed to illustrate those treatment strategies that are most effective regarding the treatment approach of oral mucositis.

Honey Against Radiation-induced Oral Mucositis in Head and Neck Cancer Patients. An Umbrella Review of Systematic Reviews and Meta- Analyses of the Literature.

Backround: Oral mucositis (OM) consists of a major side effect of radiotherapy (RT) in head and neck (H-N) cancer patients and natural honey is gaining more and more scientific interest due to its beneficial effects in tissue repair. OBJECTIVE: The aim of this review is to better clarify the preventive/therapeutic role of honey in the management of OM in patients with H-N cancer undergoing RT with or without chemotherapy (CT). METHODS: We used the PubMed database to retrieve journal articles and the inclusion criteria were only reviews and meta-analyses that illustrated the effective use of honey for either the prevention or treatment of OM in H-N cancer patients receiving either RT alone or in combination with CT. RESULTS: Our search resulted in 92 citations, of which 12 eventually fulfilled the inclusion criteria of our study. Decreased incidence and severity of OM, extended time of occurrence of mucositis, less weight loss and less treatment interruptions were occasionally documented with conventional honey use in the included reviews and meta-analyses. In contrast to conventional honey, manuka honey proved to be weak in improving OM management in the small number of included reviews in our search. CONCLUSION: Conventional honey might constitute a highly promising natural product against OM attracting much scientific interest due to its easy accessibility and low financial cost. Hence, the lack of studies with high evidence requires further advanced research to enhance the existing knowledge about the potential value of honey in radiation-induced OM in H-N cancer patients.

Evaluation of the Irradiated Volume of the Heart and Cardiac Substructures After Left Breast Radiotherapy.

Backround/Aim: Adjuvant radiotherapy in patients with cancer of the left breast may lead to impaired cardiac function. The aim of our prospective study is to evaluate (i) doses to the irradiated volume of the heart and its substructures and (ii) determine whether their correlation with changes in strain echo measurements contribute to the prediction of subclinical heart morbidity. PATIENTS AND METHODS: Twenty-five patients were enrolled in our study. We retrospectively assessed the radiation doses to the whole heart, left anterior descending artery (LAD) and left ventricle (LV). RESULTS: The mean heart dose (MHD) was 152 cGy (SD=50.56 cGy) and the range was 74-279 cGy. The LAD was the most exposed structure, with a mean dose of 448.91 cGy (SD=490.53 cGy) and range of 120-2,057cGy. Finally, the mean LV dose was 149.12 cGy (SD=69.57) with a range of 63-317 cGy. CONCLUSION: The early results of our study showed low radiation exposure of the whole heart and left ventricle, and higher exposure of the LAD. The data that will emerge from the evaluation of strain echo parameters should show whether these associations might be useful in clinical practice for the prediction of early subclinical cardiac changes.

Breast Radiotherapy and Early Adverse Cardiac Effects. The Role of Serum Biomarkers and Strain Echocardiography.

Breast cancer radiotherapy has a clear benefit for both long-term survival and local recurrence rate. However, there is still much concern about the early radiation-induced heart toxicity. This article aimed to clarify the impact of certain cardiac biomarkers and strain echocardiographic imaging on the detection of early cardiac dysfunction. Several studies that reported changes in either echocardiographic and/or serum levels measurements after breast radiotherapy were searched. Despite the established role of cardiac biomarkers to predict late cardiotoxicity after radiotherapy, data concerning early cardiac damage are still lacking. Furthermore, although strain echocardiography represents a specific tool for the detection of cardiac morbidity in certain diseases, much interest concerns its role in the prediction of early heart failure after radiotherapy. Identification of new tools for the detection of early cardiotoxicity after breast radiotherapy may minimize the side-effects of therapeutic modalities in the clinical setting.

DARPP32, STAT5 and STAT3 mRNA expression ratios in glioblastomas are associated with patient outcome.

Based on recent developments in glioblastoma subtyping, we examined DARPP32 (PPP1R1B), a neuronal marker against STAT5 and STAT3 that are pro-oncogenic in glioblastoma. mRNA ratios of DARPP32, STAT1, STAT3, STAT5A and STAT5B were assessed in routinely diagnosed gliomas s including a series of glioblastomas from patients (n = 67) treated with chemoradiotherapy (temozolomide), out of which 88 % had sequencing validated IDH-negative disease. DARPP32/STAT1 (p = 0.0007), DARPP32/STAT3 (p = 0.0004) and DARPP32/STAT5B (p = 0.0039) ratios were significantly higher in grade II and III as compared to grade IV tumours. The same high ratios were also associated with absence of immunohistochemically assessed AKT/PKB phosphorylation and survivin protein expression. High DARPP32/STAT3, DARPP32/STAT5B, and STAT5B/STAT3 ratios were associated with longer patient progression free (PFS) and overall survival (OS). Upon multivariate analysis, total/subtotal removal of the tumour (HR:0.431; 95%CI:0.241-0.771, Wald p = 0.005), high DARPP32/STAT5B (HR:0.341; 95%CI:0.169-0.690; Wald p = 0.003) and STAT5B/STAT3 mRNA ratios (HR:0.480; 95%CI:0.280-0.824; Wald p = 0.008) were independent favorable parameters for prolonged PFS. Extent of surgery (HR:0.198; 95%CI:0.101-0.390; p < 0.001) and high DARPP32/STAT5A ratios (HR:0.320; 95%CI:0.160-0.638, p = 0.001) were independently predictive for longer OS. The presented approach is applicable for prospective validation and appears promising towards an effective glioblastoma patient stratification in addition to IDH mutations. These data may contribute to understanding the biology of gliomas with respect to their potential neuronal characteristics and justify STAT-inhibiting therapeutic interventions in the same tumour system.

Initiation of GnRH antagonist on Day 1 of stimulation as compared to the long agonist protocol in PCOS patients. A randomized controlled trial: effect on hormonal levels and follicular development.

BACKGROUND The optimal time for GnRH antagonist initiation is still debatable. The purpose of the current randomized controlled trial is to provide endocrine and follicular data during ovarian stimulation for IVF in patients with polycystic ovarian syndrome (PCOS) treated either with a long GnRH agonist scheme or a fixed day-1 GnRH antagonist protocol. METHODS Randomized patients in both groups (antagonist: n = 26; long agonist: n = 52) received oral contraceptive pill treatment for three weeks and a starting dose of 150 IU of follitropin beta. The primary outcome was E(2) level on Day 5 of stimulation, while secondary outcomes were follicular development, LH during ovarian stimulation and progesterone levels. RESULTS Significantly more follicles on days 5, 7 and 8 of stimulation, significantly higher estradiol (E(2)) levels on days 1, 3, 5, 7 and 8 and significantly higher progesterone levels on days 1, 5 and 8 of stimulation were observed in the antagonist when compared with the agonist group. E(2) was approximately twice as high in the antagonist when compared with the agonist group on day 5 of stimulation (432 versus 204 pg ml(-1), P lt; 0.001). These differences were accompanied by significantly lower LH levels on days 3 and 5 and significantly higher LH levels on days 1, 7 and 8 of stimulation in the antagonist when compared with the agonist group. CONCLUSIONS In PCOS patients undergoing IVF, initiation of GnRH antagonist concomitantly with recombinant FSH is associated with an earlier follicular growth and a different hormonal environment during the follicular phase when compared with the long agonist protocol.

Administration of methylprednisolone to prevent severe ovarian hyperstimulation syndrome in patients undergoing in vitro fertilization.

OBJECTIVE: To determine whether administration of methylprednisolone to high-risk women undergoing IVF/ICSI helps reduce the development of OHSS. DESIGN: Retrospective clinical controlled study. SETTING: IVF unit. PATIENT(S): One thousand ten women who underwent IVF/ICSI from January 9, 1997, to December 31, 1999. Ninety-one patients who were at high risk for OHSS were identified by using standard criteria. INTERVENTION(S): Methylprednisolone, 16 mg/d starting on day 6 of the stimulation and tapered after the first pregnancy test (day 13 after embryo transfer). MAIN OUTCOME MEASURE(S): Occurrence of OHSS. RESULT(S): A significantly lower proportion of methylprednisolone recipients than untreated participants developed OHSS (10.0% vs. 43.9%). Treatment recipients had more oocytes retrieved and more embryos fertilized than did untreated participants. Methylprednisolone treatment was equally effective in preventing OHSS in all causes of infertility and was effective independent of the number of IVF trials and pregnancy rates. CONCLUSION(S): Treatment with methylprednisolone appears to reduce the risk for OHSS. This treatment thus helps to avoid hospitalization, reduces cycle cancellations, and improves the cost-effectiveness of IVF cycles.