Eustachian tube dysfunction: consensus statement on definition, types, clinical presentation and diagnosis

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A randomised, open-label, phase 2 study of the IDO1 inhibitor epacadostat (INCB024360) versus tamoxifen as therapy for biochemically recurrent (CA-125 relapse)-only epithelial ovarian cancer, primary peritoneal carcinoma, or fallopian tube cancer

Objective Indoleamine 2,3-dioxygenase-1 (IDO1) is a key regulator of immune tolerance in ovarian cancer. This study investigated efficacy and safety of the IDO1 enzyme inhibitor epacadostat versus tamoxifen in patients with biochemical-only recurrence (CA-125 elevation) following complete remission after first-line chemotherapy for advanced epithelial ovarian, primary peritoneal, or fallopian tube cancer. Methods In this open-label, phase 2 study (NCT01685255), patients were randomised 1:1 to epacadostat 600 mg or tamoxifen 20 mg twice daily for successive 28-day cycles and stratified by time since completion of first-line chemotherapy to first CA-125 elevation (3 to < 12 or ≥ 12 months). The primary endpoint was investigator-assessed progression-free survival (PFS; RECIST v1.1). Secondary endpoints included CA-125 response (Gynecologic Cancer InterGroup criteria), overall survival, safety, and tolerability. Results The study was terminated primarily due to slow accrual and lack of evidence of superiority. Median PFS was 3.75 months for epacadostat (n = 22) versus 5.56 months for tamoxifen (n = 20; HR, 1.34 [95% CI, 0.58–3.14]; P = 0.54). Of evaluable patients, 1 (5.0%) epacadostat and 3 (15.8%) tamoxifen patients had confirmed CA-125 responses. The most common treatment-emergent adverse event was fatigue (epacadostat, 36.4%; tamoxifen, 40.0%). Immune-related adverse events, observed with epacadostat only, were primarily rash (18.2%) and pruritus (9.1%). Epacadostat pharmacokinetics/pharmacodynamics were consistent with its known mechanism of action. IDO1 expression was observed in 94% of archival tumour samples. Conclusions This first report of immunotherapy evaluation in biochemical-only relapse ovarian cancer and of IDO1 inhibitor monotherapy in ovarian cancer found no significant difference in efficacy between epacadostat and tamoxifen. Epacadostat was generally well tolerated

High Throughput Interrogation of Somatic Mutations in High Grade Serous Cancer of the Ovary

BACKGROUND:Epithelial ovarian cancer is the most lethal of all gynecologic malignancies, and high grade serous ovarian cancer (HGSC) is the most common subtype of ovarian cancer. The objective of this study was to determine the frequency and types of point somatic mutations in HGSC using a mutation detection protocol called OncoMap that employs mass spectrometric-based genotyping technology. METHODOLOGY/PRINCIPAL FINDINGS:The Center for Cancer Genome Discovery (CCGD) Program at the Dana-Farber Cancer Institute (DFCI) has adapted a high-throughput genotyping platform to determine the mutation status of a large panel of known cancer genes. The mutation detection protocol, termed OncoMap has been expanded to detect more than 1000 mutations in 112 oncogenes in formalin-fixed paraffin-embedded (FFPE) tissue samples. We performed OncoMap on a set of 203 FFPE advanced staged HGSC specimens. We isolated genomic DNA from these samples, and after a battery of quality assurance tests, ran each of these samples on the OncoMap v3 platform. 56% (113/203) tumor samples harbored candidate mutations. Sixty-five samples had single mutations (32%) while the remaining samples had ≥ 2 mutations (24%). 196 candidate mutation calls were made in 50 genes. The most common somatic oncogene mutations were found in EGFR, KRAS, PDGRFα, KIT, and PIK3CA. Other mutations found in additional genes were found at lower frequencies (<3%). CONCLUSIONS/SIGNIFICANCE:Sequenom analysis using OncoMap on DNA extracted from FFPE ovarian cancer samples is feasible and leads to the detection of potentially druggable mutations. Screening HGSC for somatic mutations in oncogenes may lead to additional therapies for this patient population

The effects of poetry-writing SANTEL on erotic body image in remission of cancer in women: a pilot study

International audienceAbstract Aim: Our pilot study aims to describe the effects ofa new specific and structured protocol focused on poetic/erotic writing (named SANTEL) on the (re)sexualization ofbody image in women, who have experienced cancer.Procedure: The protocol consists of four steps: to choose alist of erotic verses focused on the body parts, to fill a semistructuredpoetic text, to write sentences after target phraseson the body; and in the end, to write a free poem. Mrs V.suffered from breast cancer, and one breast was removed.She and her husband participated in this poetic writing protocol,separately. We analyzed the linguistic metaphors ofthe body by QSR Nvivo10 software.Results: Using this protocol, we showed discourse variationsof metaphors before and after the experience of writing.Patient V used “I feel like an alien” as a starting metaphorto describe her cancer experience and after poetic writingsessions, she used other bodily metaphors like “My body isa flower” and “My sensual and white flesh”.Conclusion: This poetic perspective promises a type of“perceptive-literary surgery”, characterized by a sensualinvestment process after remission: a poetic reconstructionof erotic body image.Les effets d'un protocole d'écriture poétique SANTEL sur l'image érotique du corps dans le traitement du cancer féminin : étude pilote The effects of poetry-writing SANTEL on erotic body image in remission of cancer in women: a pilot study A. Santarpia · J. Tellène · M. Carrier Résumé Objectif : Cette étude pilote de type qualitative et exploratoire vise à décrire les effets d'un nouveau protocole d'écriture poético-érotique (nommée SANTEL) sur la rééro-tisation de l'image du corps chez une femme, ayant vécu un cancer. Matériel et méthodes : Il s'agit d'un protocole composé de quatre étapes : une liste des phrases à caractères poétiques et érotiques à choisir, un texte à trous à remplir, des amorces de phrases ciblées sur le corps et en fin un poème libre. Madame V. a subi un cancer du sein nécessitant une ablation complète. Madame V. et son conjoint exécutent le protocole d'écriture séparément. Nous montrons les variations discursives des métaphores utilisées avant et après l'expérience de l'écriture, à travers le logiciel d'analyse qualitative QSR NVivo10. Résultats : Madame V. passera de la métaphore initiale « je me sens une extraterrestre » vers la plus atténuée « Non. Je me dis qu'extraterrestre c'était peut-être un peu énorme ». En plus, elle utilisera de nouvelles métaphores linguistiques du corps pour raconter son image du corps telles que « ce corps de chair blanche » et « une fleur qui s'ouvre délicatement ». Conclusion : Cet exercice spécifique d'écriture promet un type de « chirurgie perceptive-littéraire » dans le processus d'investissement sensuel et affectif après la rémission, une reconstruction perceptive et poétique de l'image érotique du corps. Mots clés Métaphores perceptives · Image du corps · Cancer féminin · Corps érotique · Écriture poétique · Chirurgie perceptive-littéraire · Logiciel QSR NVivo10. Abstract Aim: Our pilot study aims to describe the effects of a new specific and structured protocol focused on poetic/ erotic writing (named SANTEL) on the (re)sexualization of body image in women, who have experienced cancer. Procedure: The protocol consists of four steps: to choose a list of erotic verses focused on the body parts, to fill a semi-structured poetic text, to write sentences after target phrases on the body; and in the end, to write a free poem. Mrs V. suffered from breast cancer, and one breast was removed. She and her husband participated in this poetic writing protocol , separately. We analyzed the linguistic metaphors of the body by QSR Nvivo10 software. Results: Using this protocol, we showed discourse variations of metaphors before and after the experience of writing. Patient V used " I feel like an alien " as a starting metaphor to describe her cancer experience and after poetic writing sessions, she used other bodily metaphors like " My body is a flower " and " My sensual and white flesh ". Conclusion: This poetic perspective promises a type of " perceptive-literary surgery " , characterized by a sensual investment process after remission: a poetic reconstruction of erotic body image. Keywords Bodily metaphors · Body image · Feminine cancer · Erotic body · Poetry writing · Perceptive-literary surgery · QSR Nvivo10 software

A meta-analytic review of stand-alone interventions to improve body image

Objective Numerous stand-alone interventions to improve body image have been developed. The present review used meta-analysis to estimate the effectiveness of such interventions, and to identify the specific change techniques that lead to improvement in body image. Methods The inclusion criteria were that (a) the intervention was stand-alone (i.e., solely focused on improving body image), (b) a control group was used, (c) participants were randomly assigned to conditions, and (d) at least one pretest and one posttest measure of body image was taken. Effect sizes were meta-analysed and moderator analyses were conducted. A taxonomy of 48 change techniques used in interventions targeted at body image was developed; all interventions were coded using this taxonomy. Results The literature search identified 62 tests of interventions (N = 3,846). Interventions produced a small-to-medium improvement in body image (d+ = 0.38), a small-to-medium reduction in beauty ideal internalisation (d+ = -0.37), and a large reduction in social comparison tendencies (d+ = -0.72). However, the effect size for body image was inflated by bias both within and across studies, and was reliable but of small magnitude once corrections for bias were applied. Effect sizes for the other outcomes were no longer reliable once corrections for bias were applied. Several features of the sample, intervention, and methodology moderated intervention effects. Twelve change techniques were associated with improvements in body image, and three techniques were contra-indicated. Conclusions The findings show that interventions engender only small improvements in body image, and underline the need for large-scale, high-quality trials in this area. The review identifies effective techniques that could be deployed in future interventions

Comparison between two methods of working length determination and its effect on radiographic extent of root canal filling: a clinical study [ISRCTN71486641]

BACKGROUND: Obtaining a correct working length is critical to the success of endodontic therapy. Different methods have been used to identify this crucial measurement. The Aim of this clinical study was to compare the effect of working length determination using apex locator alone or in combination with working length radiograph on the apical extent of root canal filling. METHODS: A total number of 66 patients, 151 canals were randomized into two groups, In group (I) working length was determined by apex locator alone, while in group (II) working length was determined by apex locator confirmed by working length radiograph, length of obturation was assessed, and the total number of radiographs was recorded. The data were analyzed using SAS system and T. tests were carried out. Statistical significance was considered to be P ≤ 0.05. RESULTS: Sixty seven canals in group I were treated with a mean distance from the tip of root canal filling to radiographic apex -0.5 mm ± 0.5 and a mean of a total number of radiographs of 2.0, while in group II eighty four canals were treated with a mean distance from the tip of root canal filling to radiographic apex -0.4 mm ± 0.5 and a mean of a total number of radiographs of 3.2. There was no statistically significant difference in the mean distance from the tip of root filling to radiographic apex between group I and group II (P > 0.05). CONCLUSION: The practice of using electronic apex locator in the determination of working length is useful and reliable with no statistical difference of the radiographic extent of root canal filling when using apex locator alone or in combination with working length radiograph. Under the clinical conditions of this study, it is suggested that the correct use of an apex locator alone could prevent the need for further diagnostic radiographs for determination of working length. This method can be useful in patients who need not to be exposed to repeated radiation because of mental, medical or oral conditions

Extended weekly dose-dense paclitaxel/carboplatin is feasible and active in heavily pre-treated platinum-resistant recurrent ovarian cancer

There is increasing evidence of the efficacy of dose-dense therapy in the management of platinum-resistant/refractory ovarian cancer. We report our experience of extended weekly carboplatin and paclitaxel in this population group. Twenty patients with platinum-resistant/refractory ovarian cancer received carboplatin AUC 3 and paclitaxel 70 mg m−2 on day 1, 8, 15 q 4 weekly for six planned cycles. Toxicity was assessed using Common Toxicity Criteria. Response was evaluated using radiological and CA125 criteria. Median age was 61 years (range 40–74 years). Median number of prior therapies is three (range 1–8). Response rate was 60% by radiological criteria (RECIST) and 76% by CA125 assessment. Grade 3 toxicities consisted of neutropenia (29% of patients) and anaemia (5%). One patient experienced grade 4 neutropenia. No grade 3/4 thombocytopaenia was reported. Fatigue, nausea and peripheral neuropathy were the most frequent non-hematological side effects. Median progression-free survival was 7.9 months and overall survival was 13.3 months. The dynamics of response to dose-dense therapy were as rapid as with front-line therapy within the same patient. This dose-dense regimen can be extended to at least 18 weekly cycles over 6 months and is well tolerated with high response rates in heavily pre-treated, platinum-resistant ovarian cancer. It forms a highly active and tolerable cytotoxic scaffold to which molecular-targeted therapies can be added in platinum-resistant ovarian cancer

Genomic activation of the EGFR and HER2-neu genes in a significant proportion of invasive epithelial ovarian cancers

<p>Abstract</p> <p>Background</p> <p>The status of the EGFR and HER2-neu genes has not been fully defined in ovarian cancer. An integrated analysis of both genes could help define the proportion of patients that would potentially benefit from targeted therapies.</p> <p>Methods</p> <p>We determined the tumour mutation status of the entire tyrosine kinase (TK) domain of the EGFR and HER2-neu genes in a cohort of 52 patients with invasive epithelial ovarian cancer as well as the gene copy number and protein expression of both genes in 31 of these patients by DGGE and direct sequecing, immunohistochemistry and Fluorescent in Situ Hybridisation (FISH).</p> <p>Results</p> <p>The EGFR was expressed in 59% of the cases, with a 2+/3+ staining intensity in 38%. HER2-neu expression was found in 35%, with a 2/3+ staining in 18%. No mutations were found in exons 18–24 of the TK domains of EGFR and HER2-neu. High polysomy of the EGFR gene was observed in 13% of the invasive epthelial cancers and amplification of the HER2-neu gene was found in 10% and correlated with a high expression level by immunohistochemistry.</p> <p>Mutations within the tyrosine kinase domain were not found in the entire TK domain of both genes, but have been found in very rare cases by others.</p> <p>Conclusion</p> <p>Genomic alteration of the HER2-neu and EGFR genes is frequent (25%) in ovarian cancer. EGFR/HER2-neu targeted therapies should be investigated prospectively and specifically in that subset of patients.</p

Motor Cortex Representation of the Upper-Limb in Individuals Born without a Hand

The body schema is an action-related representation of the body that arises from activity in a network of multiple brain areas. While it was initially thought that the body schema developed with experience, the existence of phantom limbs in individuals born without a limb (amelics) led to the suggestion that it was innate. The problem with this idea, however, is that the vast majority of amelics do not report the presence of a phantom limb. Transcranial magnetic stimulation (TMS) applied over the primary motor cortex (M1) of traumatic amputees can evoke movement sensations in the phantom, suggesting that traumatic amputation does not delete movement representations of the missing hand. Given this, we asked whether the absence of a phantom limb in the majority of amelics means that the motor cortex does not contain a cortical representation of the missing limb, or whether it is present but has been deactivated by the lack of sensorimotor experience. In four upper-limb amelic subjects we directly stimulated the arm/hand region of M1 to see 1) whether we could evoke phantom sensations, and 2) whether muscle representations in the two cortices were organised asymmetrically. TMS applied over the motor cortex contralateral to the missing limb evoked contractions in stump muscles but did not evoke phantom movement sensations. The location and extent of muscle maps varied between hemispheres but did not reveal any systematic asymmetries. In contrast, forearm muscle thresholds were always higher for the missing limb side. We suggest that phantom movement sensations reported by some upper limb amelics are mostly driven by vision and not by the persistence of motor commands to the missing limb within the sensorimotor cortex. We propose that prewired movement representations of a limb need the experience of movement to be expressed within the primary motor cortex