Cellular proliferation, cell death, and liver histology in Gambusia affinis after dietary exposure to benzidine and 2-aminofluorene.

Chronic exposure to arylamines through diet and/or smoking has been associated with genetic changes and tumorigenesis. Cellular proliferation, apoptosis, and histological changes in liver tissue were investigated in Gambusia affinis (G affinis) after chronic dietary exposure to 6.9 mM and 0.069 mM concentrations of benzidine (BZ), 2-aminofluorene (2AF), and their combination for 4, 8, and 12 weeks, respectively. The proliferation assay indicated non-dose-dependent increases in cellular proliferation over the controls for all treatment groups at 4 and 12 weeks but not at 8 weeks except for the low dose of 2AF. The apoptosis assay showed effects in the low-dose group of 2AF and BZ at 4 weeks only. Hematoxylin/eosin staining of liver tissue revealed an increase in oval/spindle cell proliferation and altered foci formation in the treated groups compared with controls. These results demonstrate a mammalian-like response to 2AF and BZ in G affinis liver.

Activation of REST/NRSF target genes in neural stem cells is sufficient to cause neuronal differentiation.

REST/NRSF is a transcriptional repressor that acts at the terminal stage of the neuronal differentiation pathway and blocks the transcription of several differentiation genes. REST/NRSF is generally downregulated during induction of neuronal differentiation. The recombinant transcription factor REST-VP16 binds to the same DNA binding site as does REST/NRSF but functions as an activator instead of a repressor and can directly activate the transcription of REST/NRSF target genes. However, it is not known whether REST-VP16 expression is sufficient to cause formation of functional neurons from neural stem cells (NSCs). Here we show that regulated expression of REST-VP16 in a physiologically relevant NSC line growing under cycling conditions converted the cells rapidly to the mature neuronal phenotype. Furthermore, when grown in the presence of retinoic acid, REST-VP16-expressing NSCs activated their target, as well as other differentiation genes that are not their direct target, converting them to the mature neuronal phenotype and enabling them to survive in the presence of mitotic inhibitors, which is a characteristic of mature neurons. In addition, these neuronal cells were physiologically active. These results showed that direct activation of REST/NRSF target genes in NSCs with a single transgene, REST-VP16, is sufficient to cause neuronal differentiation, and the findings suggested that direct activation of genes involved in the terminal stage of differentiation may cause neuronal differentiation of NSCs.

Prospective evaluation of patient satisfaction after the use of brachytherapy specific educational materials for cervical cancer.

BACKGROUND: Cervical cancer patients are faced with an enormous amount of medical information in a complex oncology field with sophisticated treatments including brachytherapy. We investigated the use of enhanced vs. standard brachytherapy-specific educational materials on patient-reported satisfaction during the informed consent process for intracavitary high-dose-rate brachytherapy. METHODS AND MATERIALS: A single-institution, prospective, randomized trial was performed to study patient-reported satisfaction with novel educational materials for high-dose-rate brachytherapy in women undergoing definitive radiation for cervical cancer. RESULTS: Fourteen women receiving informed consent with a customized educational booklet were randomized between no further intervention and take-home educational materials. The weighted average for 10 of 11 survey questions was higher in the intervention arm but ranged between 4 (agree) and 5 (strongly agree) for all questions in both arms. The mean weighted patient satisfaction scores ± standard deviations in the control arm and the intervention arms were 54.3 ± 6.4 and 57.5 ± 2.7, respectively (p = 0.26). CONCLUSIONS: Knowledge acquisition is presumed to be part of the coping process for women facing increased stress during a cancer diagnosis. A brachytherapy-specific, visual, patient-educational booklet and take-home materials used to supplement the informed consent process for high-dose-rate brachytherapy resulted in high levels of patient-reported satisfaction among women treated with cervical cancer.

A failure modes and effects analysis study for gynecologic high-dose-rate brachytherapy.

PURPOSE: To improve the quality of our gynecologic brachytherapy practice and reduce reportable events, we performed a process analysis after the failure modes and effects analysis (FMEA). METHODS AND MATERIALS: The FMEA included a multidisciplinary team specifically targeting the tandem and ring brachytherapy procedure. The treatment process was divided into six subprocesses and failure modes (FMs). A scoring guideline was developed based on published FMEA studies and assigned through team consensus. FMs were ranked according to overall and severity scores. FM ranking >5% of the highest risk priority number (RPN) score was selected for in-depth analysis. The efficiency of each existing quality assurance to detect each FM was analyzed. RESULTS: We identified 170 FMs, and 99 were scored. RPN scores ranged from 1 to 192. Of the 13 highest-ranking FMs with RPN scores >80, half had severity scores of 8 or 9, with no mode having severity of 10. Of these FM, the originating process steps were simulation (5), treatment planning (5), treatment delivery (2), and insertion (1). Our high-ranking FM focused on communication and the potential for applicator movement. Evaluation of the efficiency and the comprehensiveness of our quality assurance program showed coverage of all but three of the top 49 FMs ranked by RPN. CONCLUSIONS: This is the first reported FMEA process for a comprehensive gynecologic brachytherapy procedure overview. We were able to identify FMs that could potentially and severely impact the patient's treatment. We continue to adjust our quality assurance program based on the results of our FMEA analysis.

Implant time and process efficiency for CT-guided high-dose-rate brachytherapy for cervical cancer.

PURPOSE: This investigation details the time and teamwork required for CT-guided tandem and ring high-dose-rate brachytherapy. METHODS AND MATERIALS: From 2010 to 2012, 217 consecutive implantations were identified on 52 patients. We gathered key workflow times: preoperative, applicator insertion, CT image, treatment planning, treatment, patient recovery, and total time in clinic. Linear fixed-effects models were used, and key workflow times were the outcome variables and factors including age, body mass index, stage, outside referral, number of implant per patient, number of implants per day, and year of implantation were examined as fixed effects. RESULTS: Of the 52 patients, 62% of the patients were Fédération Internationale de Gynécologie et d'Obstétrique Stage 2B, 88% were treated with concurrent chemotherapy, and 23% were treated at an outside facility and referred for the procedure. The mean times (minutes) for each step were as follows: preoperative evaluation, 93; insertion, 23; imaging, 45; treatment planning, 137; treatment, removal, and recovery, 115; total clinic time, 401. For the insertion time, the greater implant number per patient was significantly associated with a decreased total insertion time, with and without adjusting for other covariates, p = 0.002 and p = 0.0005, respectively. Treatment planning time was expedited with increasing number of implant per patient and comparing treatment times in 2012 with those in 2010, p = 0.01 and p < 0.0001, respectively. CONCLUSIONS: Gynecologic brachytherapy requires a skillfully coordinated and efficient team approach. Identifying critical components and the time required for each step in the process is needed to improve the safety and efficiency of brachytherapy. Continuous efforts should be made to enhance the optimal treatment delivery in high-dose-rate gynecologic brachytherapy.

The development of a telemedical cancer center within the Veterans Affairs Health Care System: a report of preliminary clinical results.

In order to optimize the delivery of multidisciplinary cancer care to veterans, our institution has developed a regional cancer center with a telemedical outreach program. The objectives of this report are to describe the organization and function of the telemedical cancer center and to report our early clinical results. The Veterans Affairs Health Care System is organized into a series of integrated service networks that serve veterans within different areas throughout the United States. Within Veterans Integrated Service Network 20 (Washington, Alaska, Idaho, Oregon) we have developed a regional cancer center with telemedicine links to four outlying facilities within the service area. The telemedical outreach effort functions through the use of a multidisciplinary telemedicine tumor board. The tumor board serves patients in outlying facilities by providing comprehensive, multidisciplinary consultation for the complete range of malignancies. For individuals who do require referral to the cancer center, the tumor board serves to coordinate the logistical and clinical details of the referral process. This program has been in existence for 1 year. During that time 85 patients have been evaluated in the telemedicine tumor board. Sixty-two percent of the patients were treated at their closest facility; 38% were referred to the cancer center for treatment and/or additional diagnostic studies. The patients' diagnoses included the entire clinical spectrum of malignant disease. Preliminary clinical results demonstrate the program is feasible and it improves access to multidisciplinary cancer care. Potential benefits include improved referral coordination and minimization of patient travel and treatment delays.