Clinicopathological predictors of chemoresponsiveness in epithelial ovarian cancer: a preliminary institutional study

Objective: One-third of women with epithelial ovarian cancer are resistant to standard platinum-based chemotherapy, and insufficient data exist in predicting response to chemotherapy. We describe the clinical and pathological factors of patients with complete and incomplete response to treatment. Method: In this retrospective study, data was reviewed from 75 medical charts of 243 patients with primary epithelial ovarian cancers as a preliminary study. All patients underwent chemotherapy and cytoreductive surgery for primary disease. Fifty-six patients had complete response (CR) to chemotherapy and 19 had incomplete response (IR). Fifty-eight and 17 patients had optimal and suboptimal cytoreductive surgery, respectively. Clinical and pathological factors were compared in patients with complete and incomplete response to treatment, and optimal and suboptimal surgery. Overall survival (OS), cancer-specific survival (CSS), and time to recurrence (TTR) were estimated using the Kaplan-Meier method for patient groups. Results: The majority of patients in both the CR and IR groups were diagnosed at advanced stage ovarian cancer. The CR group had significantly lower preoperative CA125 and was more likely to have optimal chemotherapy. The CR group was also more likely to have lymph nodes removed during cytoreductive surgery. A significantly lower percentage of CR patients died from the disease and had statistically longer disease free survival. Patients who underwent suboptimal surgery had significantly shorter survival, but no difference existed in the time until recurrence between patients with optimal and suboptimal surgery. OS, CSS, and TTR were significantly increased in the CR group and in patients that had optimal surgery. Conclusion: Complete response during treatment and optimal surgery significantly increases OS, CSS, and TTR. Preoperative CA125 and lymph node removal during surgery may be predictive of complete treatment response

Ultrasound evaluation of pelvic masses seen within a university gynecologic oncology clinic: does the scan location matter?

To quantify variations in the reporting of ultrasound characteristics of adnexal masses between local ultrasound centers and a tertiary care center for women referred to gynecologic oncology for evaluation of a pelvic mass. This study also sought to evaluate whether a gynecologic oncologist’s impression regarding the suspicion for malignancy differed based upon the information provided in the local ultrasound report as compared to the tertiary care center ultrasound report

Primary radiation as initial management in endometrial cancer: investigating EBRT, IMRT and HDR brachytherapy

For patients with endometrial cancer at increased risk of perioperative morbidity, primary radiation therapy is an effective alternative treatment option. However, there has been no consensus on radiation technique and little data on outcomes. Our aim was to identify factors which determine patient selection for primary radiation, investigate treatment efficacy of radiation compared to surgical management of endometrial cancer and to evaluate different radiation modalities including external beam radiation therapy alone or with a boost of either high dose rate brachytherapy or intensity-modulated radiation therapy for differences in toxicities, recurrence-free interval, cancer-specific survival and overall survival

Small cell carcinoma of the cervix: a retrospective analysis of characteristics important in outcomes

To assess clinical characteristics and treatment modalities in patients with small cell carcinoma of the cervix and the effect this has on overall (OS) and recurrence free survival (RFS)

Multimodal perioperative pain protocol for gynecologic oncology laparotomy is associated with reduced hospital length of stay and improved patient pain scores

The primary objective was to evaluate the impact of a multimodal perioperative pain regimen on length of hospital stay for patients undergoing laparotomy with a gynecologic oncologist

Superficial versus deep lymph node dissection in early stage vulvar carcinoma

Our primary objective was to evaluate the difference in overall survival, recurrence rate, and post-operative morbidity related to superficial versus deep inguinal lymphadenectomy in squamous cell carcinoma of the vulva

Multimodal perioperative pain protocol for Gynecologic Oncology laparotomy reduces length of hospital stay

Our primary objective was to evaluate the impact of a multimodal perioperative pain regimen on length of hospital stay for patients undergoing laparotomy with a gynecologic oncologist

Social capital, social inclusion and changing school contexts: a Scottish perspective

This paper synthesises a collaborative review of social capital theory, with particular regard for its relevance to the changing educational landscape within Scotland. The review considers the common and distinctive elements of social capital, developed by the founding fathers – Putnam, Bourdieu and Coleman – and explores how these might help to understand the changing contexts and pursue opportunities for growth

HECTD2 Is Associated with Susceptibility to Mouse and Human Prion Disease

Prion diseases are fatal transmissible neurodegenerative disorders, which include Scrapie, Bovine Spongiform Encephalopathy (BSE), Creutzfeldt-Jakob Disease (CJD), and kuru. They are characterised by a prolonged clinically silent incubation period, variation in which is determined by many factors, including genetic background. We have used a heterogeneous stock of mice to identify Hectd2, an E3 ubiquitin ligase, as a quantitative trait gene for prion disease incubation time in mice. Further, we report an association between HECTD2 haplotypes and susceptibility to the acquired human prion diseases, vCJD and kuru. We report a genotype-associated differential expression of Hectd2 mRNA in mouse brains and human lymphocytes and a significant up-regulation of transcript in mice at the terminal stage of prion disease. Although the substrate of HECTD2 is unknown, these data highlight the importance of proteosome-directed protein degradation in neurodegeneration. This is the first demonstration of a mouse quantitative trait gene that also influences susceptibility to human prion diseases. Characterisation of such genes is key to understanding human risk and the molecular basis of incubation periods

Epigenetic Silencing of Host Cell Defense Genes Enhances Intracellular Survival of the Rickettsial Pathogen Anaplasma phagocytophilum

Intracellular bacteria have evolved mechanisms that promote survival within hostile host environments, often resulting in functional dysregulation and disease. Using the Anaplasma phagocytophilum–infected granulocyte model, we establish a link between host chromatin modifications, defense gene transcription and intracellular bacterial infection. Infection of THP-1 cells with A. phagocytophilum led to silencing of host defense gene expression. Histone deacetylase 1 (HDAC1) expression, activity and binding to the defense gene promoters significantly increased during infection, which resulted in decreased histone H3 acetylation in infected cells. HDAC1 overexpression enhanced infection, whereas pharmacologic and siRNA HDAC1 inhibition significantly decreased bacterial load. HDAC2 does not seem to be involved, since HDAC2 silencing by siRNA had no effect on A. phagocytophilum intracellular propagation. These data indicate that HDAC up-regulation and epigenetic silencing of host cell defense genes is required for A. phagocytophilum infection. Bacterial epigenetic regulation of host cell gene transcription could be a general mechanism that enhances intracellular pathogen survival while altering cell function and promoting disease