Cognitive impairment in gynecologic cancers: a systematic review of current approaches to diagnosis and treatment.

PURPOSE: To review the etiology and assessment of chemotherapy-related cognitive impairment (CRCI). To explore current treatment and prevention strategies for CRCI and propose future research goals in the field of gynecologic oncology. METHODS: Computerized searches in PubMed of cognitive impairment in cancer between 2000 and 2012 were conducted. The inclusion criteria were randomized control trials evaluating treatment of CRCI and search terms 'cognitive function, cognitive impairment, cognitive decline, chemobrain, chemofog, and cancer'. RESULTS: To date, numerous modalities have been utilized for assessing CRCI in patients undergoing therapy. It has been proposed to move towards web-based assessment modalities as a possible standard. Few studies have aimed to elucidate possible treatment and prevention options for CRCI; even less in the field of gynecologic oncology. Only seven of these studies were subjected to randomized control trials. Only one of these studies looked at treatment in patients with gynecologic cancers. CONCLUSIONS: The etiology of CRCI is multi-factorial. Following from this, there is no consensus on the best way to assess CRCI although objective measures are more reliable. One must extrapolate data from the non-gynecologic cancer literature, even venturing to non-cancer literature, to explore the treatment and prevention of CRCI. The methods found in these areas of research have not yet been applied to CRCI in gynecologic oncology.

Simultaneous characterization of somatic events and HPV-18 integration in a metastatic cervical carcinoma patient using DNA and RNA sequencing.

OBJECTIVE: Integration of carcinogenic human papillomaviruses (HPVs) into the host genome is a significant tumorigenic factor in specific cancers including cervical carcinoma. Although major strides have been made with respect to HPV diagnosis and prevention, identification and development of efficacious treatments for cervical cancer patients remains a goal and thus requires additional detailed characterization of both somatic events and HPV integration. Given this need, the goal of this study was to use the next generation sequencing to simultaneously evaluate somatic alterations and expression changes in a patient's cervical squamous carcinoma lesion metastatic to the lung and to detect and analyze HPV infection in the same sample. MATERIALS AND METHODS: We performed tumor and normal exome, tumor and normal shallow whole-genome sequencing, and RNA sequencing of the patient's lung metastasis. RESULTS: We generated over 1.2 billion mapped reads and identified 130 somatic point mutations and indels, 21 genic translocations, 16 coding regions demonstrating copy number changes, and over 36 genes demonstrating altered expression in the tumor (corrected P < 0.05). Sequencing also revealed the HPV type 18 (HPV-18) integration in the metastasis. Using both DNA and RNA reads, we pinpointed 3 major events indicating HPV-18 integration into an intronic region of chromosome 6p25.1 in the patient's tumor and validated these events with Sanger sequencing. This integration site has not been reported for HPV-18. CONCLUSIONS: We demonstrate that DNA and RNA sequencing can be used to concurrently characterize somatic alterations and expression changes in a biopsy and delineate HPV integration at base resolution in cervical cancer. Further sequencing will allow us to better understand the molecular basis of cervical cancer pathogenesis.

Assessing the risk of a clinically significant infection from a Microneedle Array Patch (MAP) product.

Microneedle Array Patches (MAPs) are an emerging dosage form that creates transient micron-sized disruptions in the outermost physical skin barrier, the stratum corneum, to facilitate delivery of active pharmaceutical ingredients to the underlying tissue. Numerous MAP products are proposed and there is significant clinical potential in priority areas such as vaccination. However, since their inception scientists have hypothesized about the risk of a clinically significant MAP-induced infection. Safety data from two major Phase 3 clinical trials involving hundreds of participants, who in total received tens of thousands of MAP applications, does not identify any clinically significant infections. However, the incumbent data set is not extensive enough to make definitive generalizable conclusions. A comprehensive assessment of the infection risk is therefore advised for MAP products, and this should be informed by clinical and pre-clinical data, theoretical analysis and informed opinions. In this article, a group of key stakeholders identify some of the key product- and patient-specific factors that may contribute to the risk of infection from a MAP product and provide expert opinions in the context of guidance from regulatory authorities. Considerations that are particularly pertinent to the MAP dosage form include the specifications of the finished product (e.g. microbial specification), it's design features, the setting for administration, the skill of the administrator, the anatomical application site, the target population and the clinical context. These factors, and others discussed in this article, provide a platform for the development of MAP risk assessments and a stimulus for early and open dialogue between developers, regulatory authorities and other key stakeholders, to expedite and promote development of safe and effective MAP products.

The smoking N-back: a measure of biased cue processing at varying levels of cognitive load.

INTRODUCTION: Recent cognitive models of drug addiction have emphasized attentional bias to drug-related cues. This bias manifests as increased accessibility to affect-laden drug-related content relative to less emotionally evocative stimuli and ideation. We examined whether biased processing of smoking-related content would differentially affect performance on a cognitive task as a function of smoking status and task complexity. METHODS: Twenty-one smokers and 15 nonsmokers completed increasingly difficult 1-, 2-, and 3-back versions of the Smoking N-back task. RESULTS: There were no reaction time effects that included smoking status nor was there an effect for accuracy on the 1-back task. However, smokers showed poorer accuracy on matched trials relative to nonmatched trials for smoking words on the 2- and 3-back tasks, which involve more effortful cognitive processing. Among nonsmokers, this effect was present within the 3-back condition only. CONCLUSIONS: These findings suggest that cognitive bias to drug-related cues may be modulated by task complexity. Future research on cognitive bias should better account for this factor. Additional research will be needed to validate these findings by controlling for various potential confounds (e.g., nicotine withdrawal, task fatigue) as well as determine the clinical relevance of cognitive bias across varying levels of task complexity.

Evaluation and comparison of the electrostatic dust print lifter and the electrostatic detection apparatus on the development of footwear impressions on paper.

The Electrostatic Dust Print Lifter (EDPL) and the Electrostatic Detection Apparatus(2) (ESDA(2)) were compared to determine if both processes could be used to develop footwear impressions of the same or similar quality and in what order they should be used to develop the highest quality footwear impression. The sensitivity of each technique was also evaluated. The quality of the footwear impressions developed was determined by comparing 25 individual characteristics present on the known shoe to the footwear impressions developed using each technique. The footwear impressions were made by stepping on paper placed over several different surfaces, which included: linoleum, industrial Berber carpet, nylon carpet placed over a (3/8)-in. pad, ceramic tile, cardboard, 1-in. foam, 4-in. foam, cement, asphalt, grass, and mulch. Each of the papers placed on these surfaces was developed using the EDPL before the ESDA(2) and vice versa. The sensitivity test for the ESDA(2) was conducted by processing 10 sheets of stacked paper that were stepped on with the known shoe, beginning with the top sheet. The sensitivity test for the EDPL was conducted by processing 10 sheets of paper stepped on with the known shoe in succession. This study determined the footwear impressions developed using the EDPL were of better comparative value than impressions developed with the ESDA(2). On average, 72.4% of the individual characteristics from the known impression were identified on images developed when the EDPL was used first compared with an average of 38.9% when the ESDA(2) was used first. Therefore, if only one technique is used, the EDPL should be chosen. The sensitivity test determined the ESDA(2) develops high-quality footwear impressions on only the top sheet of paper. No footwear impressions were developed on any sheets under the top sheet of paper. The sensitivity test also determined the EDPL results increase in quality as the amount of dust residue decreases on the surface.

Disparities in Vulvar Cancer Reported by the National Cancer Database: Influence of Sociodemographic Factors.

OBJECTIVE: To assess whether there is an association of patient sociodemographic factors with stage at diagnosis, treatment, and overall survival in patients with vulvar cancer in the National Cancer Database. METHODS: This was a retrospective cohort study of patients with primary squamous vulvar carcinoma identified from the National Cancer Database (1998-2004). Multivariate logistic regression was conducted to examine risk factors associated with advanced-stage (stage III or IV) disease at diagnosis. Multivariable Cox regression models were performed to explore risk factors associated with 5-year all-cause mortality. RESULTS: Of 11,153 patients, 42.3% (n=4,713) were diagnosed with stage I disease, 24.6% (n=2,745) stage II, 22.9% (n=2,556) stage III, and 10.2% (n=1,139) stage IV. Advanced stage was significantly associated with older age, nonprivate insurance, and treatment at a lower case volume center (P<.01). Of note, roughly 30% of patients with advanced-stage disease did not receive radiation therapy. Within the advanced stages, age 60 years or older and insurance type were associated with decreased survival (P<.01). In stage III disease, only black race and treatment at a community hospital were associated with a lower risk of death (P<.01). CONCLUSION: Patient sociodemographic and clinical characteristics are significantly associated with vulvar cancer stage presentation, treatment, and survival. Unfortunately, within this disease, surgical approaches and adjuvant radiation do not appear consistent. LEVEL OF EVIDENCE: II.

Extensive cutaneous metastases of ovarian cancer after prolonged response to liposomal doxorubicin.

•Cutaneous metastases are rare and clinically challenging to manage. When present, they often represent end-stage disease.•Treatments for cutaneous metastases are limited, and primarily palliative in nature.