Adoption of Universal Testing in Endometrial Cancers for Microsatellite Instability Using Next-Generation Sequencing.

PURPOSE: To assess implementation of a next-generation sequencing (NGS) assay to detect microsatellite instability (MSI) as a screen for Lynch syndrome (LS) in endometrial cancer (EC), while determining and comparing characteristics of the four molecular subtypes. METHODS: A retrospective review was performed of 408 total patients with newly diagnosed EC: 140 patients who underwent universal screening with NGS and 268 patients who underwent screening via mismatch repair immunohistochemistry (MMR IHC) as part of a historical screening paradigm. In the NGS cohort, incidental POLE and TP53 mutations along with MSI were identified and used to characterize EC into molecular subtypes: POLE-ultramutated, MSI high (MSI-H), TP53-mutated, and no specific molecular profile (NSMP). In historical cohorts, age- and/or family history-directed screening was performed with MMR IHC. Statistical analysis was performed using a t-test for continuous variables and chi-square or Fisher's exact test for categorical variables. RESULTS: In the NGS cohort, 38 subjects (27%) had MSI-H EC, 100 (71%) had microsatellite stable EC, and two (1%) had an indeterminate result. LS was diagnosed in two subjects (1%), and all but five patients completed genetic screening (96%). Molecular subtypes were ascertained: eight had POLE-ultramutated EC, 28 had TP53-mutated EC (20%), and 66 (47%) had NSMP. MSI-H and TP53-mutated EC had worse prognostic features compared with NSMP EC. Comparison with historical cohorts demonstrated a significant increase in follow-up testing after an initial positive genetic screen in the MSI NGS cohort (56% v 89%; P = .001). CONCLUSION: MSI by NGS allowed for simultaneous screening for LS and categorization of EC into molecular subtypes with prognostic and therapeutic implications.

Are Columnar Cell Lesions the Earliest Non-Obligate Precursor in the Low-Grade Breast Neoplasia Pathway?

Columnar cell lesions (CCLs) of the breast comprise a spectrum of morphologic alterations of the terminal duct lobular unit involving variably dilated and enlarged acini lined by columnar epithelial cells. The World Health Organization currently classifies CCLs without atypia as columnar cell change (CCC) and columnar cell hyperplasia (CCH), whereas flat epithelial atypia (FEA) is a unifying term encompassing both CCC and CCH with cytologic atypia. CCLs have been increasingly recognized in stereotactic core needle biopsies (CNBs) performed for the assessment of calcifications. CCLs are believed to represent the earliest non-obligate precursor of low-grade invasive breast carcinomas as they share molecular alterations and often coexist with entities in the low-grade breast neoplasia pathway. Despite this association, however, the risk of progression of CCLs to invasive breast carcinoma appears low and may not exceed that of concurrent proliferative lesions. As the reported upgrade rates of pure CCL/FEA when identified as the most advanced high-risk lesion on CNB vary widely, the management of FEA diagnosed on CNB remains controversial. This review will include a historical overview of CCLs and will examine histologic diagnostic criteria, molecular alterations, prognosis and issues related to upgrade rates and clinical management.

Outcome-based Validation of Confluent/Expansile Versus Infiltrative Pattern Assessment and Growth-based Grading in Ovarian Mucinous Carcinoma.

The growth pattern (confluent/expansile versus infiltrative) in primary ovarian mucinous carcinoma (OMC) is prognostically important, and the International Collaboration on Cancer Reporting (ICCR) currently recommends recording the percentage of infiltrative growth in this tumor type. Histologic grading of OMC is controversial with no single approach widely accepted or currently recognized by the World Health Organization Classification of Tumours. Since ovarian carcinoma grade is often considered in clinical decision-making, previous literature has recommended incorporating clinically relevant tumor parameters such as growth pattern into the OMC grade. We herein validate this approach, termed Growth-Based Grade (GBG), in an independent, well-annotated cohort from 2 institutions. OMCs with available histologic material underwent review and grading by Silverberg, International Federation of Obstetrics and Gynecology (FIGO), and GBG schema. GBG categorizes OMCs as low-grade (GBG-LG, confluent/expansile growth, or ≤10% infiltrative invasion) or high-grade (GBG-HG, infiltrative growth in >10% of tumor). The cohort consisted of 74 OMCs, 53 designated as GBG-LG, and 21 as GBG-HG. Using Silverberg grading, the cohort had 42 (57%) grade 1, 28 (38%) grade 2, and 4 (5%) grade 3 OMCs. Using FIGO grading, 50 (68%) OMCs were grade 1, 23 (31%) grade 2, and 1 (1%) grade 3. Follow-up data was available in 68 patients, of which 15 (22%) had cancer recurrence. GBG-HG tumors were far more likely to recur compared with GBG-LG tumors (57% vs. 6%; χ 2P <0.0001). Silverberg and FIGO grading systems also correlated with progression-free survival in univariate analysis, but multivariate analysis showed only GBG to be significant (hazard ratio: 10.9; Cox proportional regression P =0.0004). Seven patients (10%) died of disease, all of whom had GBG-HG (log-rank P <0.0001). Multivariate analysis showed that the percentage of infiltrative growth was the only factor predictive of disease-specific survival (hazard ratio: 25.5, Cox P =0.02). Adding nuclear atypia to GBG categories did not improve prognostication. Our study validates the prognostic value of the GBG system for both disease-free survival and disease-specific survival in OMC, which outperformed Silverberg and FIGO grades in multivariate analysis. Thus, GBG should be the preferred method for tumor grading.

Benign Metastasizing Leiomyoma in the Lung Presenting in a Phyllodes-Like Pattern Mimicking a Biphasic Tumor: A Case Report.

Primary biphasic tumors of the lung are rare. Lung lesions with a biphasic pattern are far more commonly primary or metastatic soft tissue tumors with entrapped native respiratory epithelium, giving the false impression of a biphasic tumor. We report a case of bilateral benign metastasizing leiomyomas in a 69-year-old female where the tumor cells diffusely entrapped native respiratory glands in a phyllodes-like pattern. The radiographic characteristics and histologic appearance were not immediately diagnostic and covered a wide differential. Reaching the final diagnosis required the use of immunohistochemical studies as well as correlation with the patient's history and radiographic findings. To the best of our knowledge, this is the first report of pulmonary benign metastasizing leiomyoma presenting in a phyllodes-like pattern. This case illustrates the importance of considering entrapment of native lung epithelium in the differential diagnosis of biphasic-appearing lung tumors.

SRY-box transcription factor 10 is a highly specific biomarker of basal-like breast cancer.

AIMS: Basal-like breast cancer is an aggressive molecular subtype associated with younger age and early relapse. Most cases lack expression of oestrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2, limiting targeted therapeutic options. Basal-like breast cancer is defined by the expression of genes in the outer/basally located epithelial layer of mammary glands, including those encoding cytokeratin (CK) 5 and CK14, and epidermal growth factor receptor (EGFR). SRY-box transcription factor 10 (SOX10), for which there is a readily available immunohistochemical stain, is expressed in a subset of breast cancers, particularly triple-negative carcinomas. In this study, we sought to: (i) assess the association between SOX10 expression and intrinsic molecular subtypes as defined by Prediction Analysis of Microarray 50 (PAM50) gene expression; and (ii) compare the performance of SOX10 with that of other surrogate markers of the basal-like subtype, including CK5, EGFR, nestin, and inositol polyphosphate 4-phosphatase type II (INPP4B). METHODS AND RESULTS: SOX10 immunostaining was performed on tissue microarrays constructed from a contemporary series enriched for ER-negative and weakly ER-positive cancers that had also undergone PAM50 gene profiling. A total of 211 cases were informative for both SOX10 immunohistochemistry and PAM50 subtype, including 103 basal-like cancers. Staining for SOX10 was positive in 73 of 103 basal-like cancers and in only two of 108 cancers of other subtypes (P < 0.001), resulting in a sensitivity of 70.9% and a specificity of 98.1%. SOX10 was more specific than the other tested basal markers, and the results were independent of ER status. CONCLUSIONS: SOX10 is a moderately sensitive, but highly specific, immunohistochemical biomarker for the basal-like intrinsic subtype of breast cancer, which, unlike other commonly used immunohistochemical biomarkers, is independent of hormone receptor status.

Androgenetic/Biparental Mosaic/Chimeric Conceptions With a Molar Component: A Diagnostic and Clinical Challenge.

Hydatidiform moles (HM) are gestational trophoblastic diseases which arise due to an imbalance in genetic material and which are morphologically characterized by enlarged and irregular chorionic villi and trophoblastic hyperplasia, among other features. The morphologic differential diagnosis for HM encompasses a number of entities including androgenetic/biparental mosaic/chimeric (ABMC) conceptions, an interesting duo of lesions with a nonmolar form (placental mesenchymal dysplasia) and a molar form (typically with a complete HM component). ABMC conceptions contain a mixture of 2 cell populations (1 androgenetic and 1 biparental) and arise as a result of mosaicism (mitotic error in a zygote) or chimerism (fusion of 2 zygotes). Because of their unique molecular underpinnings, these rare lesions show a number of findings including the presence of multiple villous populations, discordant p57 immunostaining, and mixed genotypes. ABMC conceptions are important to accurately diagnose as the molar form in particular carries a risk for persistent gestational trophoblastic diseases and thus requires appropriate treatment and follow-up. In this report, we provide detailed characterizations of 2 such cases of ABMC conceptions with a molar component. Both patients (ages 34 and 31) were in the first trimester of pregnancy and had ultrasound findings concerning for HM. Increased comprehension of the pathogenesis and morphology of ABMC conceptions, combined with ancillary techniques including p57 immunohistochemistry, fluorescence in situ hybridization, and molar genotyping, has allowed us to accurately and efficiently identify these lesions. However, a number of pitfalls exist which may lead to misdiagnosis.

Ulipristal Acetate Prior to Surgery for Endometriosis.

Selective progesterone receptor modulators may have a role in the treatment of endometriosis. The aim of this report is to review the effect of ulipristal acetate (UPA) on endometriosis lesions and symptoms in women treated prior to surgery. A pathology review of eutopic endometrium and endometriotic lesions was conducted by two gynecologic pathologists. The main outcome measures reported are pain reduction, amenorrhea, and pathologic progesterone receptor modulator-associated endometrial changes (PAECs). Overall, fifteen women with endometriosis received UPA over a 27-month study period. UPA was administered in an intermittent fashion in the majority of patients while 27% of patients had continuous treatment, between 6 and 24 months. Eleven (73%) patients reported amenorrhea on UPA and 11 (92%) of 12 patients with pain reported pain reduction or resolution. Fourteen patients (93%) proceeded with surgical management. Thirteen (93%) patients underwent excision of suspected endometriosis at surgery. Twelve cases (86%) had concurrent eutopic endometrium specimens and PAEC was identified in 58% (n = 7). Among the 14 cases that underwent surgery, a total of 49 extraovarian sites were sampled. Endometriosis was definitively identified in 31 (63%) of these sites. Three cases (21%) showed morphologic features similar to PAEC within foci of endometriosis. All cases of PAEC-like features in endometriosis also had PAEC in the endometrium. These patients had all noted pain reduction and amenorrhea preoperatively. In conclusion, PAECs may be found in endometriosis lesions in patients treated with UPA. Further prospective investigation is required to evaluate the efficacy and safety of SPRMs in women with endometriosis.

Evaluation of Intraoperative Assessments in the Management of Endometrial Carcinoma: A Retrospective Quality Assurance Review.

Intraoperative assessment (IA) of uteri is often used to help determine whether to perform lymphadenectomy in patients with endometrial carcinoma. We sought to perform a quality assurance review of the practice of IA at our institution. In a 1-yr period, 107 hysterectomies had an IA performed. Grade of neoplasm in preoperative endometrial biopsy, neoplasm size, depth of myometrial invasion at IA, operative management, and final histologic features were recorded. Operative reports were reviewed to assess the surgeon's interpretation of the IA and the effect on surgical management. The sensitivity and specificity for IA of deep myometrial invasion (>50% myometrial thickness) compared with final histology was 76.9% and 91.1%. The positive predictive value was 71.4%, negative predictive value 93.2% and accuracy 88%. Neoplasm size was provided in 47% of cases. In 10% of patients lymphadenectomy was performed despite low-risk features. IA results were included in the operative report in 87% of cases. There were differences in 8.4% of cases between the IA diagnosis and the surgeon's operative report. IA of deep myometrial invasion is reliable at our institution. Several metrics for quality improvement have been identified as a result of this retrospective review. These include but are not limited to more reliable reporting of neoplasm size, documentation, and communication with gynecologic oncologists.

The Influence of Acculturation on Traumatic Stress Following Childbirth Among Hispanic Adolescents.

INTRODUCTION: Many studies have explored the role of acculturation on health outcomes; however, no studies to date have examined relationships between acculturation and the traumatic stress of childbirth among Hispanic adolescents. METHOD: A convenience sample of 66 Hispanic adolescents 13 to 19 years of age completed the Acculturation Rating Scale for Mexican Americans-II (ARSMA-II), a demographic sheet, birth appraisal scale, and the Impact of Event Scale within 72 hours of birth. RESULTS: Significant associations were found between the ARSMA-II subscales and acculturation proxy variables, excluding language; however, only the Mexican Orientation Subscale and generation proxy variable influenced the birth experience. The study findings showed that Hispanic adolescents reporting a more traumatic childbirth identified closer with the Mexican culture and reported fewer family generations residing in the United States. CONCLUSION: As an overlooked area of research, our findings support the need for additional research related to the traumatic stress of birth among Hispanic adolescents. Using multiple acculturation measurements, including the ARSMA-II, with larger, more diverse samples of adolescents, equally balanced between all categories of acculturation and placement within the five-tier generation matrix, can provide some insightful information and directed health care.

Experiences of Women With Gestational Trophoblastic Neoplasia Treated With High-Dose Chemotherapy and Stem Cell Transplantation: A Qualitative Study.

PURPOSE/OBJECTIVES: To explore the experiences of women with gestational trophoblastic neoplasia during and after treatment to understand their perspectives, priorities, and concerns.
. RESEARCH APPROACH: A descriptive, exploratory study using in-depth semistructured interviews.
. SETTING: All interviews were conducted in a quiet, designated room at Weston Park Hospital in Sheffield, South Yorkshire.
. PARTICIPANTS: Women with gestational trophoblastic neoplasia who had received stem cell transplantation from 2003 to 2013. Ten patients were eligible, and eight agreed to participate.
. METHODOLOGIC APPROACH: Interviews were carried out over the phone and were recorded and transcribed verbatim. Framework analysis was carried out to generate in-depth descriptions of participants' experiences.
. FINDINGS: Participants described significant physical, psychological, and social effects during and following treatment. Recovery was slow, and treatment had long-term effects on sexuality and body image. The impact of the women's diagnosis and treatment on their children was a primary concern.
. INTERPRETATION: The study provided insight into the multidimensional impact of stem cell transplantation, which can continue after treatment. The need for family-centered services for patients with dependent children was identified.
. IMPLICATIONS FOR NURSING: Nurses need to develop services that effectively communicate the challenges of stem cell transplantation to patients and provide family-centered care and late effects and rehabilitation services.

Epithelioid angiosarcoma arising in a uterine leiomyoma with associated elevated CA-125: A case report.

We describe the case of a 67 year old female with longstanding uterine leiomyomas who presented with fatigue, weight loss, elevated CA-125 and an enlarging mass arising from the posterior uterine fundus. Histologic sections of the mass contained a leiomyoma with interspersed foci of malignant epithelioid cells forming anastomosing vascular channels. The neoplastic cells were diffusely positive for CD31 and FLI1, supporting the morphologic impression of epithelioid angiosarcoma. Few cases of epithelioid angiosarcoma arising within a leiomyoma have been described. In this report we discuss this association and describe its relation with elevated CA-125.

Implementation of a Transition of Care Coordinator at a Military Treatment Facility.

UNLABELLED: A patient's transition from the inpatient to the outpatient setting is complex and prone to medical errors. This subsequently increases patient morbidity and cost to the healthcare system. METHODS: Our quality improvement initiative used a licensed clinical social worker from within a Family Medicine residency clinic to serve as a Transitions of Care Coordinator (TOCC) with the goal of decreasing patient morbidity and system cost. RESULTS: The number of documented patient contacts by our primary care office in the postdischarge period increased significantly after implementation of the TOCC (3.1% vs 40.2%, P=.01). Pearson correlation during our postimplementation period suggested an inverse relationship between contact by a TOCC and emergency department (ED) and hospital utilization rates (r=-0.68, P=.05 and r=0.062, P=.005, respectively). However, the percentage of ED visits (11.9% vs 20.8%, P=.02) and hospital readmissions (5.6% vs 13.7%, P=.01) significantly increased overall between the pre-and postimplementation periods. CONCLUSIONS: The implementation of a TOCC within a military Family Medicine residency clinic significantly increased the frequency of ED visits and readmissions to the inpatient service for patients discharged from the Family Medicine inpatient service.

Immunohistochemical characterization of appendiceal mucinous neoplasms and the value of special AT-rich sequence-binding protein 2 in their distinction from primary ovarian mucinous tumours.

AIMS: The distinction between primary ovarian mucinous tumours and appendiceal mucinous neoplasms metastatic to the ovary can be challenging, given the overlap of morphological features and immunohistochemical expression of traditional markers. Special AT-rich sequence-binding protein 2 (SATB2) has recently been described as a sensitive and specific marker of colorectal epithelium. This study was to determine its expression in appendiceal mucinous tumours and its role in their distinction from ovarian neoplasms. METHODS AND RESULTS: Immunohistochemistry was performed in tissue microarrays from 32 primary appendiceal mucinous tumours (25 low-grade appendiceal mucinous neoplasms and seven adenocarcinomas) and 40 ovarian mucinous neoplasms (20 borderline tumours and 20 adenocarcinomas). Stains were interpreted as positive or negative by scoring intensity and distribution. SATB2 was positive in 93.8% of appendiceal tumours and in only one ovarian tumour; SATB2 was 97.5% specific for appendiceal origin. CK20, CDX2 and MUC2 were strongly and diffusely positive in appendiceal tumours; ovarian tumours were also positive, but with a patchy distribution and mild intensity. CK7 was expressed in 97.5% of ovarian tumours and in 31.2% of appendiceal tumours. PAX8 was positive in 70% of ovarian tumours, and negative in all appendiceal lesions. CONCLUSIONS: SATB2 is frequently expressed in appendiceal mucinous neoplasms. In the context of a mucinous neoplasm involving the ovary, any SATB2 positivity should raise the possibility of appendiceal origin. Expression of CK20, CDX2 and MUC2 supports appendiceal origin only when diffuse and strong. These and other markers, such as CK7 and PAX8, are recommended in the work-up of ovarian mucinous tumours with any clinical or pathological features suggestive of secondary origin.

Immunohistochemistry in the Diagnosis of Mucinous Neoplasms Involving the Ovary: The Added Value of SATB2 and Biomarker Discovery Through Protein Expression Database Mining.

Immunohistochemistry is frequently used to identify ovarian mucinous neoplasms as primary or metastatic; however, there is significant overlap in expression patterns. We compared traditional markers (CK7, CK20, CDX2, PAX8, estrogen receptor, ß-catenin, MUC1, MUC2, and MUC5AC) to 2 novel proteins identified through mining of the Human Protein Atlas expression database: SATB2 and POF1B. The study cohort included 49 primary gastrointestinal (GI) mucinous adenocarcinomas (19 colorectal, 15 gastric, 15 pancreatobiliary), 60 primary ovarian mucinous neoplasms (19 cystadenomas, 21 borderline tumors, 20 adenocarcinomas), and 19 metastatic carcinomas to the ovary (14 lower and 5 upper GI primaries). Immunohistochemistry was performed on tissue microarrays, scored and interpreted as negative (absent or focal/weak) or positive. Metastatic tumors were frequently unilateral (42.8% of tumors from lower and 40% of tumors from upper tract) and ≥10 cm (85.7% of tumors from lower and 80% of tumors from upper tract). CK7 was positive in 88.5% upper GI and 88.3% primary ovarian compared with 24.3% lower GI neoplasms. CK20 and CDX2 were positive in 84.8% and 100% of lower GI tumors, respectively; however, expression was also common in upper GI (CK20 42.8%, CDX2 50%) and primary ovarian neoplasms (CK20 65.7%, CDX2 38.3%). Conversely, SATB2 was more specific for lower GI origin, being positive in 78.8% lower GI but only 11.5% upper GI and 1.7% primary ovarian neoplasms. PAX8 expression was common in primary ovarian neoplasms (75% of all neoplasms, 65% of carcinomas); only 1 (1.5%) GI tumor was positive. MUC2 and ß-catenin were frequently positive in lower GI tumors (96.9% and 51.5%, respectively). Estrogen receptor expression was only seen in primary ovarian neoplasms (13.3%). Nuclear premature ovarian failure 1B (POF1B) expression was seen in malignant tumors regardless of their origin. A panel including CK7, SATB2, and PAX8 separated primary from secondary GI neoplasms with up to 77.1% sensitivity and 99% specificity, outperforming tumor laterality and size. Second-line markers such as CDX2, MUC2, estrogen receptor, MUC1, and ß-catenin increased the sensitivity of immunohistochemistry in excluding lower GI origin. Biomarker search using proteomic databases has a value in diagnostic pathology, as shown with SATB2; however, as seen with POF1B, expression profiles in these databases are not always reproduced in larger cohorts.

Fatal foreign-body granulomatous pulmonary embolization due to microcrystalline cellulose in a patient receiving total parenteral nutrition: all crystals are not what they seem.

Pulmonary foreign-body granulomatous embolization has been described secondary to crystal precipitation in total parenteral nutrition (TPN) as well as when pharmaceutical tablets are crushed and injected intravenously. Extensive granulomatous embolization may cause pulmonary hypertension and death due to acute cor pulmonale. We report the case of a 34-year old woman who had been receiving TPN post-operatively secondary to complications of a paraesophageal hernia repair. During and following receiving TPN, she experienced episodes of hypoxia, tachycardia, fever, and hypotension. Computed tomography scans of the thorax showed centrilobular nodules, tree-in-bud and ground-glass opacities, as well as findings of pulmonary hypertension. Following an episode of hypoxia she was found unresponsive and died despite resuscitative efforts. Microscopic examination of the lungs following post-mortem examination revealed occlusive granulomatous inflammation of the pulmonary arterial vasculature by crystalline material. The morphologic and histochemical patterns of the crystals were suggestive of microcrystalline cellulose, a finding that was confirmed by energy dispersive X-spectroscopy and infrared spectroscopy. Ancillary tests did not support that the crystalline material was the result of TPN precipitation. Foreign-body granulomatous embolization leading to acute core pulmonale may occur as a complication of both intravenous injection of oral medications as well as of TPN crystallization. The source of crystalline material may be difficult to discern based solely on morphological assessment or by histochemical staining. Ancillary studies such as energy dispersive X-spectroscopy or infrared spectroscopy should be performed to definitively discern the two entities.

Effect of early pregnancy following chemotherapy on disease relapse and fetal outcome in women treated for gestational trophoblastic neoplasia.

OBJECTIVE: To examine the effects of early pregnancy (< 12 months following chemotherapy) on a recent cohort of women treated with modern therapies for gestational trophoblastic neoplasia (GTN). STUDY DESIGN: The Charing Cross GTN database was screened between 1998-2012 to identify 1,204 patients treated with either single-agent (61.9%) or multiagent (38.1%) chemotherapy. RESULTS: A total of 23% of single-agent and 15.4% of the multiagent treatment groups conceived within 12 months of chemotherapy, resulting in 255 early pregnancies, with 73.3% resulting in live births. There was no significant increased risk of miscarriage, ectopic pregnancy, second molar pregnancy or stillbirth as compared to the general U.K. population. Intriguingly, the incidence of relapse was only 1.7% in the early pregnancy group as compared to 5.2% in the 963 patients who did not conceive early. CONCLUSION: Women who become pregnant within 12 months postchemotherapy for GTN can be reassured of a likely favorable outcome, although the safest option is still to delay pregnancy for a year.

Where there is no paramedic: the Sachigo Lake Wilderness Emergency Response Education Initiative.

Aaron Orkin and colleague describe their collaboration that developed, delivered, and studied a community-based first response training program in a remote indigenous community in northern Canada.

Evaluation of a multiple ecological level child obesity prevention program: Switch what you Do, View, and Chew.

BACKGROUND: Schools are the most frequent target for intervention programs aimed at preventing child obesity; however, the overall effectiveness of these programs has been limited. It has therefore been recommended that interventions target multiple ecological levels (community, family, school and individual) to have greater success in changing risk behaviors for obesity. This study examined the immediate and short-term, sustained effects of the Switch program, which targeted three behaviors (decreasing children's screen time, increasing fruit and vegetable consumption, and increasing physical activity) at three ecological levels (the family, school, and community). METHODS: Participants were 1,323 children and their parents from 10 schools in two states. Schools were matched and randomly assigned to treatment and control. Measures of the key behaviors and body mass index were collected at baseline, immediately post-intervention, and 6 months post-intervention. RESULTS: The effect sizes of the differences between treatment and control groups ranged between small (Cohen's d = 0.15 for body mass index at 6 months post-intervention) to large (1.38; parent report of screen time at 6 months post-intervention), controlling for baseline levels. There was a significant difference in parent-reported screen time at post-intervention in the experimental group, and this effect was maintained at 6 months post-intervention (a difference of about 2 hours/week). The experimental group also showed a significant increase in parent-reported fruit and vegetable consumption while child-reported fruit and vegetable consumption was marginally significant. At the 6-month follow-up, parent-reported screen time was significantly lower, and parent and child-reported fruit and vegetable consumption was significantly increased. There were no significant effects on pedometer measures of physical activity or body mass index in the experimental group. The intervention effects were moderated by child sex (for fruit and vegetable consumption, physical activity, and weight status), family involvement (for fruit and vegetable consumption), and child body mass index (for screen time). The perception of change among the experimental group was generally positive with 23% to 62% indicating positive changes in behaviors. CONCLUSION: The results indicate that the Switch program yielded small-to-modest treatment effects for promoting children's fruit and vegetable consumption and minimizing screen time. The Switch program offers promise for use in youth obesity prevention.

SWITCH: rationale, design, and implementation of a community, school, and family-based intervention to modify behaviors related to childhood obesity.

BACKGROUND: Although several previous projects have attempted to address the issue of child obesity through school-based interventions, the overall effectiveness of school-based programs on health-related outcomes in youth has been poor. Thus, it has been suggested that multi-level interventions that aim to influence healthy lifestyle behaviors at the community, school and family levels may prove more successful in the prevention of childhood obesity. METHODS/DESIGN: This paper describes the rationale, design, and implementation of a community-, school-, and family-based intervention aimed at modifying key behaviors (physical activity, screen time (Internet, television, video games), and nutrition) related to childhood obesity among third through fifth graders in two mid-western cities. The intervention involves a randomized study of 10 schools (5 intervention and 5 control schools). The intervention is being conducted during the duration of the academic year - approximately 9 months - and includes baseline and post-intervention measurements of physical activity, dietary intake, screen time and body composition. DISCUSSION: We hope this report will be useful to researchers, public health professionals, and school administrators and health professionals (nurses and physical/health educators) seeking to develop similar prevention programs. It is obvious that more collaborative, inter-disciplinary, multi-level work is needed before a proven, effective intervention package to modify behaviors related to childhood obesity can be generally recommended. It is our hope that SWITCH is a step in that direction. TRIAL REGISTRATION: ClinicalTrials.gov NCT00685555.