Trends in health information seeking among cancer and non-cancer adults between 2003 and 2005: A descriptive analysis of Health Information National Trends Survey (HINTS) data

Cancer is the second leading cause of death in the United States. With the advent of new technologies, changes in health care delivery, and multiplicity of provider types that patients must see, cancer care management has become increasingly complex. The availability of cancer health information has been shown to help cancer patients cope with the management and effects of their cancers. As a result, more cancer patients are using the internet to find resources that can aid in decision-making and recovery. ^ The Health Information National Trends Survey (HINTS) is a nationally representative survey designed to collect information about the experiences of cancer and non-cancer adults with health information sources. The HINTS survey focused on both conventional sources as well as newer technologies, particularly the internet. This study is a descriptive analysis of the HINTS 2003 and HINTS 2005 survey data. The purpose of the research is to explore the general trends in health information seeking and use by US adults, and especially by cancer patients. ^ From 2003 to 2005, internet use for various health-related activities appears to have increased among adults with and without cancer. Differences were found between the groups in the general trust in information media, particularly the internet. Non-cancer respondents tended to have greater trust in information media than cancer respondents. ^ The latter portion of this work examined characteristics of HINTS respondents that were thought to be relevant to how much trust individuals placed in the internet as a source of health information. Trust in health information from the internet was significantly greater among younger adults, higher-earning households, internet users, online seekers of health or cancer information, and those who found online cancer information useful. ^

Management and outcomes of anorectal infection in the cancer patient

Background. The objective of this retrospective cohort study is to examine the presentation and outcomes for a contemporary series of cancer patients with anorectal infection. In addition, we seek to identify factors which are associated with surgical intervention. ^ Methods. The study cohort was identified from ICD-9 codes for diagnosis of infection of the anal and rectal region and patients who underwent a surgical oncology consultation between 1/2000 and 12/2006. Clinical presentation, treatment rendered, and outcomes were retrospectively recorded. ^ Results. Of the 100 patients evaluated by the surgical oncology service for anorectal infection, 42 were treated non-operatively and 58 underwent surgical intervention. Factors associated with surgical intervention based on logistic multivariable analysis included the diagnosis of an abscess (odds ratio [OR] 10.5; 95% confidence interval [CI] 2.9-38.5) and the documentation of erythema on physical examination (OR 3.1; 95% CI 1.1-8.4). Thrombocytopenia (platelets < 50,000) was associated with non-operative management (OR 0.3; 95% CI 0.1-0.7). Incision and drainage was the most common surgical procedure (79%) while a wide debridement for a necrotizing soft tissue infection was required in 2 patients. Infection-specific 90-day mortality was only 1% (N=1). However, the median overall survival for the entire cohort was only 14.4 months (95% CI 7.9-19.5). ^ Conclusions. Non-operative management is a reasonable treatment option for anorectal infection in patients with cancer. Identification of an abscess, erythema on physical exam, and thrombocytopenia were associated with management strategy. Although rare, necrotizing soft tissue infections are associated with significant mortality. ^

Role of IkappaB kinase beta in inflammation-mediated breast cancer development

Breast cancer is the second most common farm of cancers and the second leading cause of cancer death for American women. Clinical studies indicate inflammation is a risk factor for breast cancer development. Among the cytokines and chemokines secreted by the infiltrating inflammatory cells, tumor necrosis factor a (TNFα) is considered one of the most important inflammatory factors involved in inflammation-mediated tumorigenesis. ^ Here we found that TNFα/IKKβ signaling pathway is able to increase tumor angiogenesis through activation of mTOR pathway. While investigating which molecule in the mTOR pathway involved in TNFα/IKKβ-mediated mTOR activation, our results showed that IKKβ physically interacts with and phosphorylates TSC1 at Ser487 and Ser511 in vitro and in vivo. Phosphorylation of TSC1 by IKKβ inhibits its association with TSC2, alters TSC2 membrane localization, and thereby activates mTOR. In vitro angiogenesis assays and orthotopic breast cancer model reveals that phosphorylation of TSC1 by IKKβ enhances VEGF expression, angiogenesis and culminates in tumorigenesis. Furthermore, expression of activated IKKβ is associated with TSC1 Ser511 phosphorylation and VEGF production in multiple tumor types and correlates with poor clinical outcome of breast cancer patients. ^ Furthermore, dysregulation of tumor suppressor FOXO3a contributes to the development of breast cancer. We found that overexpression of IKKβ led to inhibition of FOXO3a-mediated transactivation activity. While investigating the underlying mechanisms of IKKβ-mediated dysregulation of FOXO3a, our results showed that IKKβ physically associated with FOXO3a and phosphorylated FOXO3a at Ser644 in vitro and in vivo. The phosphorylation of FOXO3a by IKKβ altered its subcellular localization from nucleus to cytoplasm and promoted its degradation through ubiquitin-proteasome pathway. Mutation of FOXO3a at Ser644 prevented IKKβ-induced ubiquitination and degradation. In vitro cell proliferation assay and orthotopic breast cancer model revealed that phosphorylation of FOXO3a by IKKβ overrode FOXO3a-mediated repression of tumor progression. ^ In conclusion, our findings identify IKKβ-mediated suppressions of both TSC1 and FOXO3a are critical for inflammation-mediated breast cancer development through increasing tumor angiogenesis and evading apoptosis, respectively. Understanding the role of IKKβ in both FOXO3a and TSC/mTOR signaling pathways provides a critical insight of inflammation-mediated diseases and may provide a target for clinical intervention in human breast cancer. ^

The effect of African Americans' ethnographic paradigms and cultural explanatory model of breast cancer in framing the male partner's attitudes and behaviors about the woman's breast cancer diagnosis

The disparate burden of breast cancer-related morbidity and mortality experienced by African American women compared with women of other races is a topic of intense debate in the medical and public health arenas. The anomaly is consistently attributed to the fact that at diagnosis, a large proportion of African American women have advanced-stage disease. Extensive research has documented the impacts of cultural factors and of socioeconomic factors in shaping African American women's breast-health practices; however, there is another factor of a more subtle influence that might have some role in establishing these women's vulnerability to this disease: the lack of or perceived lack of partner support. Themes expressed in the research literature reflect that many African American breast cancer patients and survivors consider their male partners as being apathetic and nonsupportive. ^ The purpose of this study was to learn how African American couples' ethnographic paradigms and cultural explanatory model of breast cancer frame the male partners' responses to the women's diagnosis and to assess his ability to cope and willingness to adapt to the subsequent challenges. The goal of the study was to determine whether these men's coping and adaptation skills positively or negatively affect the women's self-care attitudes and behaviors. ^ This study involved 4 African American couples in which the woman was a breast cancer survivor. Participants were recruited through a community-based cancer support group and a church-based cancer support group. Recruitment sessions were held at regular meetings of these organizations. Accrual took 2 months. In separate sessions, each male partner and each survivor completed a demographic survey and a questionnaire and were interviewed. Additionally, the couples were asked to participate in a communications activity (Adinkra). This activity was not done to fulfill any part of the study purpose and was not included in the data analysis; rather, it was done to assess its potential use as an intervention to promote dialogue between African American partners about the experience of breast cancer. ^ The questionnaire was analyzed on the basis of a coding schema and the interview responses were analyzed on the principles of hermeneutic phenomenology. In both cases, the instruments were used to determine whether the partner's coping skills reflected a compassionate attitude (positive response) versus an apathetic attitude (negative response) and whether his adaptation skills reflected supportive behaviors (the positive response) versus nonsupportive behaviors (the negative response). Overall, the women's responses showed that they perceived of their partners as being compassionate, yet nonsupportive, and the partner's perceived of themselves likewise. Only half of the women said that their partners' coping and adaptation abilities enabled them to relinquish traditional concepts of control and focus on their own well-being. ^ The themes that emerged indicate that African American men's attitudes and behaviors regarding his female partner's diagnosis of breast cancer and his ability to cope and willingness to adapt are influenced by their ritualistic mantras, folk beliefs, religious teachings/spiritual values, existential ideologies, socioeconomic status, and environmental factors and by their established perceptions of what causes breast cancer, what the treatments and outcomes are, and how the disease affects the entire family, particularly him. These findings imply that a culturally specific intervention might be useful in educating African American men about breast cancer and their roles in supporting their female partners, physically and psychologically, during diagnosis, treatment, and recovery. ^

Application of cell line based genomic predictors to predict response to targeted therapies in breast cancer

Cancer cell lines can be treated with a drug and the molecular comparison of responders and non-responders may yield potential predictors that could be tested in the clinic. It is a bioinformatics challenge to apply the cell line-derived multivariable response predictors to patients who respond to therapy. Using the gene expression data from 23 breast cancer cell lines, I developed three predictors of dasatinib sensitivity by selecting differentially expressed genes and applying different classification algorithms. The performance of these predictors on independent cell lines with known dasatinib response was tested. The predictor based on weighted voting method has the best overall performance. It correctly predicted dasatinib sensitivity in 11 out of 12 (92%) breast and 17 out of 23 (74%) lung cancer cell lines. These predictors were then applied to the gene expression data from 133 breast cancer patients in an attempt to predict how the patients might respond to dasatinib therapy. Two predictors identified 13 patients in common to be dasatinib sensitive. Sixty two percent of these cases are triple negative (ER-negative, HER2-negative and PR-negative) and 76% are double negative. The result is consistent with the findings from other studies, which identified a target population for dasatinib treatment to be triple negative or basal breast cancer subtype. In conclusion, we think that the cell line-derived dasatinib classifiers can be applied to the human patients. ^

Near infra-red-activatable nanocarriers for selective cancer diagnosis and treatment

Standard treatment strategies for cancer patients include surgery, radiation therapy, and chemotherapy. Although these strategies have been proven effective, they also have associated limitations. An attractive and innovative approach that can be used alone or in combination with the above modalities is based on the systemic or topical administration of a nanomaterial-based photoactive compound. Interaction with light in the near infrared (NIR) region results in either emission of fluorescence, which can be used for photodetection, or absorption of light which results in phototherapy. Nanomaterials have the advantage of providing multi-functional and unique properties in a single device that cannot be readily acquired with conventional small molecular weight compounds. ^ In this study, three different novel nanocarrier systems were designed and evaluated in mediating photodetection and phototherapy in the NIR. The first compound synthesized was a dual-labeled magnetic resonance/optical imaging agent for sentinel lymph node mapping and biopsy. This dual-labeled agent combines the high resolution of magnetic resonance imaging with the highly sensitive detection of optical imaging. The second imaging agent was an activatable optical imaging agent used to monitor cathepsin B activity in vivo and to probe the degradation of poly(L-glutamic acid). This polymeric nanocarrier offers highly sensitive technique for the detection of enzymatic activity, with is not yet possible with small molecular weight compounds. The third agent was a C225-conjugated hollow nanoshell that is targeted to epidermal growth factor receptors. This targeting agent has been demonstrated to mediate photothermal therapy both in vitro and in vivo. ^ These nanocarrier systems are an invaluable tool for the detection of cancer and many other diseases. With improved targeted delivery of these agents, the ability to diagnose diseases will become more sensitive and more specific. Finally, when designed properly, these agents would allow concurrent diagnosis and treatment of patients of various diseases. ^

A new fork for clinical application: Targeting forkhead transcription factors in cancer therapy

RAS-ERK-MAPK (Mitogen-activated protein kinase) pathway plays an essential role in proliferation, differentiation, and tumor progression. In this study, we showed that ERK downregulated FOXO3a through directly interacting with and phosphorylating FOXO3a at Serine 294, Serine 344, and Serine 425. ERK-phosphorylated FOXO3a was degraded by MDM2-mediated ubiquitin-proteosome pathway. FOXO3a phosphorylation and degradation consequently promoted cell proliferation and tumorigenesis. However, the non-phosphorylated FOXO3a mutant, which was resistant to the interaction and degradation by MDM2, resulted in inhibition of tumor formation. Forkhead O transcription factors (FOXOs) are important in the regulation of cellular functions including cell cycle arrest and cell death. Perturbation of FOXOs function leads to deregulated cell proliferation and cancer. Inactivation of FOXO proteins by activation of cell survival pathways, such as PI3K/AKT/IKK, is associated with tumorigenesis. Our study will further highlight FOXOs as new therapeutic targets in a broad spectrum of cancers. ^ Chemotherapeutic drug resistance is the most concerned problem in cancer therapy as resistance ultimately leads to treatment failure of cancer patients. In another study, we showed that blocking ERK activity with AZD6244, an established MEK1/2 inhibitor currently under human cancer clinical trials, enhances FOXO3a expression in various human cancer cell lines in vitro, and also in human colon cancer cell xenografts in vivo. Knocking down FOXO3a and its downstream gene Bim impaired AZD6244-induced growth suppression, whereas restoring activation of FOXO3a sensitized human cancer cell to AZD6244-induced growth arrest and apoptosis. More importantly, AZD6244-resistant cancer cells showed impaired endogenous FOXO3a nuclear translocation, reduced FOXO3a-Bim promoter association and significantly decreased Bim expression in response to AZD6244. AZD6244-resistant cancer cells can be sensitized to API-2 (an AKT inhibitor) and LY294002 (a PI3K inhibitor) in suppressing cell growth and colony formation, these inhibitors were known to enhance FOXO3a activity/nuclear translocation through inhibiting PI3K-AKT pathway. This study reveals novel molecular mechanism contributing to AZD6244-resistance through regulation of FOXO3a activity, further provides significant clinical implication of combining AZD6244 with PI3K/AKT inhibitors for sensitizing AZD6244-resistant cancer cells by activating FOXO3a. FOXO3a activation can be an essential pharmacological target and indicator to mediate and predict AZD6244 efficacy in clinical use. ^

Role of ovarian cancer antigen CA125/MUC16 in development and cancer

Cancer antigen 125 (CA125) is a tumor antigen that is routinely used to monitor the disease progress and the outcome of treatment in ovarian cancer patients. Elevated serum levels of CA125 are detected in over 80% of epithelial ovarian cancer patients. CA125 is a high molecular weight (>1M Dalton) mucin-type glycoprotein encoded by the MUC16 gene on human chromosome 19. Although MUC16 has served as the best serum marker for monitoring growth of ovarian cancer, roles for MUC16 in normal physiology and ovarian cancer are largely unknown. To understand the biological functions of MUC16, I characterized a mouse Muc16 homolog on chromosome 9 by means of expression pattern profiling, phenotype analysis of Muc16 knockout mice, and in vitro and in vivo studies of Muc16 null transformed ovarian surface epithelial (OSE) cells. ^ The mouse Muc16 homolog shares a conserved genomic structure with human MUC16. In addition to being expressed in mouse ovarian cancer, mouse Muc16 mRNA and protein were expressed in the mesothelia covering the heart, lung, ovary, oviduct, spleen, testis, and uterus. The conserved genomic structure and expression pattern of mouse Muc16 to human MUC16 suggests that mouse Muc16 is the ortholog of human MUC16. To understand the biological functions of Muc16, I generated Muc16 knockout mice. Muc16 knockout mice were viable, fertile and normal by one year of age. However, between 18 and 24 months of age, Muc16 knockout mice developed various tissue abnormalities such as ovarian cysts and tumors of the liver and other peritoneal organs. To determine the role of MUC16 in ovarian cancer progression, I established Muc16 null transformed ovarian surface epithelial (OSE) cell lines, following the same method to develop mouse model of epithelial ovarian cancer (Orsulic et al., 2002). Loss of Muc16 did not affect cell morphology, cell proliferation rate, or tumorigenic potential. However, Muc16-null OSE cells showed decreased attachment to extracellular matrix proteins as well as to primary mouse peritoneal mesothelial cells. Peritoneal mesothelia are the most frequent implantation sites of ovarian cancer. Furthermore, a pilot transplantation assay suggests that Muc16 null transformed OSE cells formed less disseminated tumors in the peritoneal cavity compared to wild-type OSE cells. ^ In conclusion, these results demonstrate that MUC16 is not required for normal mouse development or reproduction, but plays important roles in tissue homeostasis, ovarian cancer cell adhesion and dissemination. This study provides the first in vivo evidence of the roles of MUC16 in development, as well as ovarian cancer progression and dissemination. These studies offer valuable insights into possible mechanisms of ovarian cancer development and potential molecular targets for ovarian cancer treatment. ^

The role of cardiovascular comorbidities in ovarian cancer survival

Objective. One facet of cancer care that often goes ignored is comorbidities, or diseases that exist in concert with cancer. Comorbid conditions may affect survival by influencing treatment decisions and prognosis. The purpose of this secondary data analysis was to identify whether a history of cardiovascular comorbidities among ovarian cancer patients influenced survival time at the University of Texas M. D. Anderson Cancer Center. The parent study, Project Peace, has a longitudinal design with an embedded randomized efficacy study which seeks to improve detection of depressive disorders in ovarian, peritoneal, and fallopian tube cancers. ^ Methods. Survival time was calculated for the 249 ovarian cancer patients abstracted by Project Peace staff. Cardiovascular comorbidities were documented as present, based upon information from medical records in addition to self reported comorbidities in a baseline study questionnaire. Kaplan-Meier survival curves were used to compare survival time among patients with a presence or absence of particular cardiovascular comorbidities. Cox Regression proportional models accounted for multivariable factors such as age, staging, family history of cardiovascular comorbidities, and treatment. ^ Results. Among our patient population, there was a statistically significant relationship between shorter survival time and a history of thrombosis, pericardial disease/tamponade, or COPD/pulmonary hypertension. Ovarian cancer patients with a history of thrombosis lived approximately half as long as patients without thrombosis (58.06 months vs. 121.55 months; p=.001). In addition, patients who suffered from pericardial disease/tamponade had poorer survival than those without a history of pericardial disease/tamponade (48 months vs. 80.07 months; p=.002). Ovarian cancer patients with a history of COPD or pulmonary hypertension had a median survival of 60.2 months, while the median survival for patients without these comorbidities was 80.2 months (p=.014). ^ Conclusion. Especially because of its relatively lower survival rate, greater emphasis needs to be placed on the potential influence of cardiovascular comorbid conditions in ovarian cancer.^

Quality of life, symptom experience, and use of complementary and alternative medicine among women with ovarian cancer

The objectives of this dissertation were to determine the quality of life in women with ovarian cancer and the association of their physical and emotional well-being with the number of symptoms, duration of symptoms, and the scores of common symptoms of ovarian cancer; to study the prevalence of complementary and alternative medicine techniques for symptom relief and its association with the number of symptoms, age, education, insurance, comorbidity, and satisfaction with medical care they received, and their pre-diagnostic experience of symptoms.^ This study was based on a secondary data analysis of a study of early detection of ovarian cancer. A sample of 139 women with ovarian cancer was recruited and was administered a questionnaire comprised of questions on their quality of life, their symptoms and what they did about the symptoms, whether they used any complementary and alternative medicine techniques, and other medical conditions they had. Out of this sample, 53 patients underwent in-depth interviews relating to their symptoms before the diagnosis and their experiences with the health care system leading to the ovarian cancer diagnosis. ^ In article #1, ovarian cancer patients were observed to have significantly poorer quality of life on all subscales and summary scores except pain, compared to that of the general population of US women. Physical well-being scores were negatively associated with the number of symptoms before diagnosis and a significant negative association of comorbidity index was observed with physical well-being. Higher education and increase in time since diagnosis was found to have better physical scores. Emotional well-being scores showed marginally significant associations with number of symptoms and bloating. ^ In article #2, a thematic content analysis of the ovarian cancer patients’ interviews revealed that on recognition of their symptoms women first assumed their symptoms to be a normal transient occurrence due to a pre-existing disease condition, or due to some other disease. A series of misattributions of their symptoms on their and their doctors’ part impacted their health care seeking.In article #3, a significantly greater likelihood of CAM use with an increase in the number of symptoms was observed.^ Based on the foregoing results, it is important to educate women on possible signs of ovarian cancer and also to educate doctors about the results of current research regarding ovarian cancer diagnosis. This will help to avoid a delay in getting a diagnosis and improve women’s quality of life. It emphasizes the diagnosis of ovarian cancer in earlier stages by more sensitive screening techniques. This study emphasizes the importance of consideration of comorbidity in any quality of life research. Additionally, educating women in the safe use of CAM techniques carries immense significance because the efficacy and safety of many of the currently advertized CAM products has not been scientifically validated. Further research is needed to confirm the findings of this study. ^

Physical activity among breast and prostate cancer survivors: Barriers, facilitators and maintenance following the FRESH START trial

Research provides evidence of the positive health effects associated with regular physical activity participation in all populations. Activity may prove to be especially beneficial in those with chronic conditions such as cancer. However, the majority of cancer patients and survivors do not participate in the recommended amount of physical activity. The purpose of this dissertation was to identify factors associated with physical activity participation, describe how these factors change as result of a diet and exercise intervention, and to evaluate correlates of long term physical activity maintenance. ^ For this dissertation, I analyzed data from the FRESH START trial, a randomized, single-blind, phase II clinical trial focused on improving diet and physical activity among recently diagnosed breast and prostate cancer survivors. Analyses included both parametric and non-parametric statistical tests. Three separate studies were conducted, with sample sizes ranging from 400 to 486. ^ Common barriers to exercise, such as “no willpower,” “too busy,” and “I have pain,” were reported among breast and prostate cancer survivors; however, these barriers were not significantly associated with minutes of physical activity. Breast cancer survivors reported a greater number of total barriers to exercise as well as higher proportions reporting individual barriers, compared to prostate cancer survivors. Just less than half of participants reduced their total number of barriers to exercise from baseline to 1-year follow-up, and those who did reduce barriers reported greater increases in minutes of physical activity compared to those who reported no change in barriers to exercise. Participants in both the tailored and standardized intervention groups reported greater minutes of physical activity at 2-year follow-up compared to baseline. Overall, twelve percent of participants reached recommended levels of physical activity at both 1- and 2-year follow-up. Self-efficacy was positively associated with physical activity maintenance, and the number of total barriers to exercise was inversely associated with physical activity maintenance. ^ Results from this dissertation are novel and informative, and will help to guide future physical activity interventions among cancer survivors. Thoughtfully designed interventions may encourage greater participation in physical activity and ultimately improve overall quality of life in this population. ^

Genetic susceptibility, cigarette smoking, and wood dust exposure in lung cancer: Case control analyses

This case control study was conducted to assess the association between lung cancer risk, mutagen sensitivity (a marker of cancer susceptibility), and a putative lung carcinogen, wood dust exposure. There were 165 cases (98 African-Americans, 67 Mexican-Americans) with newly diagnosed, previously untreated lung cancer, and 239 controls, frequency-matched on age, sex, and ethnicity.^ Mutagen sensitivity ($\ge$1 break/cell) was associated with a statistically significant elevated risk for lung cancer (odds ratio (OR) = 4.1, 95% confidence limits (CL) = 2.3,7.2). Wood dust exposure was also a significant predictor of risk (OR = 2.8, 95% CL = 1.2,6.6) after controlling for smoking and mutagen sensitivity. When stratified by ethnicity, wood dust exposure was a significant risk factor for African-Americans (OR = 4.0, 95% CL = 1.4,11.5), but not for Mexican-Americans (OR = 1.5, 95% CL = 0.3,7.1). Stratified analysis suggested a greater than multiplicative interaction between wood dust exposure and both mutagen sensitivity and smoking.^ The cases had significantly more breaks on chromosomes 4 and 5 than the controls did with ORs of 4.9 (95% CL = 2.0, 11.7) and 3.9 (95% CL = 1.6, 9.3), respectively. Breaks at 4p14, 4q27, 4q31, 5q21-22, 5q31, and 5q33 were significantly more common in lung cancer patients than in controls. Lung cancer risk had a dose-response relationship with breaks on chromosomes 4 and 5. Cigarette smoking had a strong interaction with breaks on chromosomes 2, 4, and 5.^ In a molecular cytogenetic study, using chromosome painting and G-banding, we showed that: (1) the proportion of chromosome 5 abnormalities surviving as chromosome-type aberrations remained significantly higher in cells of lung cancer cases (14%) than in controls (5%) (P $<$ 0.001). However, no significant differences were detected in chromosome 4 abnormalities between cases and controls; (2) the proportion of chromosome 5q13-22 abnormalities was 5.3% in the cases and 0.7% in the controls (P $<$ 0.001). 5q13-22 regions represented 40% of all abnormalities on chromosome 5 in the cases and only 14% in the controls.^ This study suggests that mutagen sensitivity, wood dust exposure, and cigarette smoking were independent risk factors for lung cancer, and the susceptibility of particular chromosome loci to mutagenic damage may be a genetic marker for specific types of lung cancer. ^

Evaluating alternative therapies. Support/imagery and immune function in breast cancer: A pilot study

Cancer patients increasingly request alternative therapies such as imagery techniques and support groups. Although research suggests evidence of enhanced psychosocial functioning with supportive group therapy and enhanced immune function with imagery techniques, studies are anecdotal or limited to case studies or descriptive reports. The efficacy of these alternative therapies should be validated by randomized, controlled trials and the mechanisms of action mediating immune function and outcome examined.^ In a 12-month pilot study, we evaluate the feasibility of conducting a controlled study with clinical trial methodology to test the effects of imagery/relaxation and support on quality of life, emotional well-being, and immune function for women after breast cancer. Using a randomized pre-post test design with three intervention waves, we assigned women (n = 47) to either standard care (n = 15), standard care plus 6-weekly support sessions (n = 16) or imagery/relaxation sessions (n = 16).^ The primary aim of this pilot study is to determine the feasibility of conducting a clinical trial of alternative therapies in a clinical care setting. Secondary aims are to determine parameter estimates for the effects of the two treatment groups on quality of life, coping, social support, and immune function and describe methodology issues related to trials of alternative therapies.^ The research provides direction for future studies of alternative therapies by describing the recruitment, clinical trial experience, and related methodology issues. The study extends previous work by differentiating the effects of support group from mental imagery among outpatient groups who are homogeneous regarding cancer type and treatment stage. The study provides data for future longitudinal studies of disease progression by differentiating the effectiveness of interventions designed to enhance quality of life, coping, social support, and immune function and subsequently, alter the clinical course of disease. ^

Anesthetic choices and breast cancer recurrence: A retrospective cohort study of risk factors

Background: The impact of anesthetic techniques for breast cancer surgery traditionally has been centered on the incidence of acute pain syndromes and complications immediately after surgery. Evaluating anesthesia management beyond short-term effects is an emerging science. Several animal studies have concluded that regional anesthesia independently reduces cancer recurrence and metastasis. A small number of retrospective clinical studies indicate that reductions in cancer recurrence are attributable to anesthesia technique; however, individual risk factors need to be taken into consideration. ^ Purpose: The aims were to: 1) investigate differences in patient, disease and treatment factors between women who received surgical treatment for breast cancer with paravertebral regional and general anesthesia compared to women who received general anesthesia alone; 2) explore patient, disease and treatment factors associated with recurrence of breast cancer; and 3) test the association between type of anesthesia and breast cancer recurrence and survival over 22–46 months following surgery. ^ Methods: This retrospective cohort study included 358 patients with stage 0-III disease who received a partial or total mastectomy without axillary node dissection between October 2006 and October 2008 at a large academic cancer center. Follow-up ended in August 2010 with a median follow-up time of 28.8 months. ^ Results: The patient demographics were equally represented across anesthesia groups. Mean BMI (kg/m2) was greater for the patients who received general anesthesia (GA) alone (29±6.8) compared to those that received paravertebral regional block (PVB) with GA (28±5.1), p=0.001. The PVB with GA group had more advanced stages of disease (p=0.01) and longer surgeries (p=0.01) than the GA only group. Breast cancer recurrence was detected in only 1.7% of the study population. The mean age was 51±18 in those who had a recurrence compared to 58±11 in the non-recurrent group (p=0.06). Overall, no association between anesthesia type and recurrence was found (p=0.53), with an unadjusted estimated hazard ratio of 1.84 (95% CI 0.34–10.08). ^ Conclusions: In contrast to previous retrospective studies in cancer patients receiving surgical and anesthesia treatment, this study was unable to detect a difference in relating type of anesthesia with decreased breast cancer recurrence. Nonetheless, a significant association between BMI and type of anesthesia was observed and should be taken into account in future studies. Because the overall rate of recurrence was very small in this population, a larger study would be needed to detect any differences in rates of recurrence attributable to type of anesthesia. ^

A systematic review of clostridium difficile infection in patients with iatrogenic immunesuppression

Background: Incidence of C. difficile infection (CDI) has increased dramatically in the past decade and is the most frequent cause of nosocomial infectious diarrhea. The outcome of infection may range from mild diarrhea to life-threatening pseudomembranous colitis depending on the immunological response of the host, which is highly compromised in this special population that includes bone marrow transplant (BMT), solid organ transplant (SOT) and cancer patients on cytotoxic chemotherapy. ^ Objectives: We conducted a meta-analysis to assess the incidence rates of CDI and the time to onset of infection in patients with iatrogenic immune suppression. ^ Methods: Original studies were identified through an extensive search of electronic databases including PubMed, Ovid Medline (R), RefWorks and Biological Abstracts and their references. The overall incidence rate of CDI in the immune suppressed population was calculated using random effects model and their 95% confidence interval was derived. Differences in the incidence of CDI and time to onset of infection were calculated between the groups and within the groups. Publication bias was assessed using a funnel plot. Results: Twenty nine published articles involving 7,424 patients met the eligibility requirements. The overall incidence of CDI in the immune suppressed population is 11.1% (95% Confidence Interval (CI): 9.2–13.4%). The incidence of CDI was higher in SOT patients (14.2%, 95% CI: 6.8–21.5%); (p-value-0.022) and in cancer patients on cytotoxic chemotherapy (11.4%, 95% CI: 8.4–15.4%); (p = 0.042) than in BMT patients (10.5%, 95% CI: 7.9–13.1%). In a subgroup analysis of BMT population, the incidence of CDI is significantly higher in patients who received allogeneic BMT (15.1%, 95% CI: 11.2–20.0%; p value <0.0001). Similarly, in the SOT population, the incidence of CDI was higher in patients who underwent liver transplantation (11.0%, 95% CI: 5.6–20.3%); (p= 0.0672). The median time to onset of infection was shorter in BMT patients (p=0.0025). ^ Conclusions: It is evident from the combined analysis of these 29 published studies that the incidence of CDI in the immune suppressed population is higher. However, early diagnosis and treatment of CDI will help reduce the morbidity and mortality due to CDI in this special population.^