Tina Hernandez-Boussard

Abstract

To examine hospital resources associated with patient outcomes for aortic valve replacement (AVR), including inpatient adverse events and mortality.We used the Nationwide Inpatient Sample to identify AVR procedures from 1998 to 2010 and the American Hospital Association Annual Survey to augment hospital characteristics. Primary outcomes included mortality and the development of adverse events, identified using standardized patient safety indicators (PSI). Patient and hospital characteristics associated with PSI development were evaluated using univariate and multivariate analyses.An estimated 410,157 AVRs at 5009 hospitals were performed in the US between 1998 and 2010. The number of procedures grew annually by 4.72% (p = 0.0003) in high volume hospitals, 4.48% in medium volume hospitals (p < 0.0001), and 2.03% in low volume hospitals (p = 0.154). Mortality was highest in low volume hospitals, 4.70%, decreased from 4.14% to 3.73% in medium and high volume hospitals, respectively (p = 0.0002). Rates of PSIs did not vary significantly across volume terciles (p = 0.254). Multivariate logistic regression analysis showed low volume hospitals had increased risk of mortality as compared with high volume hospitals (odds ratio [OR]: 1.42; 95% confidence interval [CI]: 1.01 to 2.00), while hospital volume was not associated with adverse events. PSI development was associated with small hospitals as compared with large (OR: 1.63, 95% CI: 1.16 to 2.28) and inversely associated with higher nurse-to-patient ratio (OR: 0.94, 95% CI: 0.90 to 0.99).The volume-outcomes relationship was associated with mortality outcomes but not postoperative complications. We identified structural differences in hospital size, nurses-to-patient ratio, and nursing skill level indicative of high quality outcomes.

View details for DOI 10.1111/jocs.12284

View details for PubMedID 24417274

Abstract

The unclear relationship of obesity to incident melanoma and nonmelanoma skin cancer (NMSC) risks was evaluated in the large, geographically diverse longitudinal, prospective Women's Health Initiative (WHI) observational study. Risks of melanoma and NMSC in normal weight women were compared with risks in overweight [body mass index (BMI) = 25-29.0 kg/m(2)] and obese (BMI ≥ 30 kg/m(2)) women, using Cox proportional hazards models for melanoma and logistic regression for NMSC. Over a mean 9.4 years of follow-up, there were 386 melanoma and 9,870 NSMC cases. Risk of melanoma did not differ across weight categories (P = 0.86), whereas in fully adjusted models, NMSC risk was lower in overweight [OR, 0.93; 95% confidence interval (CI), 0.89-0.99] and obese (OR, 0.85; 95% CI, 0.80-0.91) women (P < 0.001). Excess body weight was not associated with melanoma risk in postmenopausal women but was inversely associated with NMSC risk, possibly due to lower sun exposure in overweight and obese women. This supports previous work demonstrating the relationship between excess body weight and skin cancer risk. Cancer Epidemiol Biomarkers Prev; 22(12); 2412-5. ©2013 AACR.

View details for DOI 10.1158/1055-9965.EPI-13-0647

View details for PubMedID 24042260

Abstract

Breast reconstruction improves quality-of-life of breast cancer patients. Different reconstructive options exist, yet commentary in the plastic surgery literature suggests that financial constraints are limiting access to autologous reconstruction (AR). This study follows national trends in breast reconstruction and identifies factors associated with reconstructive choices. Data were obtained from the Nationwide Inpatient Sample from 1998 to 2008. Patients were categorized as having either implant or ARs. Bivariate and multivariate regression analysis identified variables associated with receiving implants versus AR. Physician fee schedules were analyzed using national average Medicare physician reimbursement rates. From 1998 to 2008, 324,134 breast reconstructions were performed. Reconstructions increased 4% per year. The proportion of implant reconstructions increased 11% per year, whereasARs decreased 5% per year (p < 0.05). Our model showed that the odds of having implant-based versus AR were significantly associated with age, disease severity, payer type, hospital teaching status, and year of surgery. Year of surgery was the strongest predictor of implant reconstruction; patients receiving breast reconstructive surgery in 2009 were three times more likely to have implant breast reconstructive surgery compared with similar patients in 2002. Medicare reimbursement steadily declined for AR over a similar time frame. From 1998 to 2008, autologous breast reconstruction has significantly declined, parallel to a decrease in physician reimbursement. Our data found no significant change in patient characteristics supporting the lack of choice of AR. Further research is warranted to better understand this shift to implant reconstruction and to ensure future access of these complex reconstructive procedures.

View details for DOI 10.1111/tbj.12148

View details for PubMedID 23758582

View details for Web of Science ID 000322759500074

Abstract

To assess how common it is to have multiple overlapping meta-analyses of randomized trials published on the same topic.Survey of published meta-analyses.PubMed.Meta-analyses published in 2010 were identified, and 5% of them were randomly selected. We further selected those that included randomized trials and examined effectiveness of any medical intervention. For eligible meta-analyses, we searched for other meta-analyses on the same topic (covering the same comparisons, indications/settings, and outcomes or overlapping subsets of them) published until February 2013.Of 73 eligible meta-analyses published in 2010, 49 (67%) had at least one other overlapping meta-analysis (median two meta-analyses per topic, interquartile range 1-4, maximum 13). In 17 topics at least one author was involved in at least two of the overlapping meta-analyses. No characteristics of the index meta-analyses were associated with the potential for overlapping meta-analyses. Among pairs of overlapping meta-analyses in 20 randomly selected topics, 13 of the more recent meta-analyses did not include any additional outcomes. In three of the four topics with eight or more published meta-analyses, many meta-analyses examined only a subset of the eligible interventions or indications/settings covered by the index meta-analysis. Conversely, for statins in the prevention of atrial fibrillation after cardiac surgery, 11 meta-analyses were published with similar eligibility criteria for interventions and setting: there was still variability on which studies were included, but the results were always similar or even identical across meta-analyses.While some independent replication of meta-analyses by different teams is possibly useful, the overall picture suggests that there is a waste of efforts with many topics covered by multiple overlapping meta-analyses.

View details for DOI 10.1136/bmj.f4501

View details for Web of Science ID 000322247400002

View details for PubMedID 23873947

Abstract

Lumpectomy is performed in a small but growing proportion of men with breast cancer. It is unknown whether men undergoing breast-conserving surgery (BCS) receive care compliant with breast cancer treatment guidelines. Patients with breast cancer in the surveillance, epidemiology, and end results (SEER) database who underwent lumpectomy between 1983 and 2009 were identified. Gender differences in the receipt of lymph node staging and adjuvant radiation therapy were assessed. Multivariate logistic regression was utilized to evaluate the independent association of gender on these outcomes. The influence of gender on breast cancer-specific survival (BCSS) was analyzed. 382,030 of 824,408 (46.3 %) women compared to 712 of 6,039 (11.8 %) men with breast cancer underwent lumpectomy. Men were older, more likely to be black, less likely to have stage I disease and more likely to have stage IV disease. Only 59.2 % of men had lymph nodes sampled at the time of surgery compared to 81.6 % of women (p < 0.0001). In addition, only 35.4 % of men received adjuvant breast radiation therapy compared to 69.8 % of women (p < 0.0001). After controlling for age, race, stage, grade, and year of diagnosis, female gender was significantly associated with receiving adjuvant radiation therapy (OR 2.9, 95 % CI 2.4-3.4) and lymph node staging (OR 1.6, 95 % CI 1.3-1.90). Five- and ten-year BCSS were 88.0 and 83.5 % for men compared to 93.2 and 88.2 % for women (p < 0.001). Men with breast cancer are less likely to receive lymph node staging or adjuvant radiation therapy following BCS compared to women.

View details for DOI 10.1007/s10549-013-2517-y

View details for PubMedID 23572298

Abstract

Although mastectomy is considered the gold standard for male breast cancer (MBC), the utilization of lumpectomy and its impact on outcomes in MBC patients has not been previously studied.The Surveillance, Epidemiology and End Results (SEER) database was used to identify all MBC patients who underwent either mastectomy or less than mastectomy (i.e., lumpectomy) between 1983 and 2009.A total of 4707 (86.8 %) men underwent mastectomy and 718 (13.2 %) underwent lumpectomy. A greater proportion of patients underwent lumpectomy later in the study period (1983 to 1986, 10.6 %, vs. 2007 to 2009, 15.1 %). A greater percentage of lumpectomy patients were 80 years or older (21.3 % vs. 16.3 %), had stage IV disease (7.3 % vs. 3.1 %), and received no lymph node sampling (34.3 % vs. 6.9 %). Only 35.4 % of patients underwent adjuvant radiotherapy after lumpectomy. Ten-year breast cancer-specific survival and overall survival were 82.8 % and 46.9 %, respectively, in lumpectomy patients vs. 77.3 % and 46.4 %, respectively, in mastectomy patients. On Cox proportional hazards regression, lumpectomy was not independently associated with worse breast cancer-specific survival (odds ratio 1.09, 95 % confidence interval 0.87-1.37) or overall survival (odds ratio 1.12, 95 % confidence interval 0.98-1.27) after controlling for age, race, stage, and grade, as well as whether radiotherapy was received.Lumpectomy is performed in a small but growing proportion of MBC patients. These patients are not only older and more likely to have advanced disease at the time of diagnosis, but they also are less likely to receive standard of care therapy, such as lymph node sampling and adjuvant radiotherapy. Despite these observations, breast cancer-specific survival is unaffected by the type of surgery.

View details for DOI 10.1245/s10434-013-2918-5

View details for Web of Science ID 000317308200021

View details for PubMedID 23460016

Abstract

The rising incidence of nonmelanoma skin cancer (NMSC) is well documented, but data are limited on the number of visits and treatment patterns of NMSC in the outpatient setting.To evaluate practice and treatment patterns of NMSC in the United States over the last decade and to characterize differences according to sex, age, race, insurance type, and physician specialty.Adults with an International Classification of Diseases, Ninth Revision, diagnosis of NMSC were included in this cross-sectional survey study of the National Ambulatory Medical Care Survey between 1995 and 2007. Primary outcomes included population-adjusted NMSC visit rates and odds ratios of receiving a procedure for NMSC using logistic regression.Rates of NMSC visits increased between 1995 and 2007. The number of visits was significantly higher in men, particularly those aged 65 and older. Fifty-nine percent of NMSC visits were associated with a procedure, and the individuals associated with that visit were more likely to be male, to be seen by a dermatologist, and to have private-pay insurance.Nonmelanoma skin cancer visit rates increased from 1995 to 2007 and were higher in men than women. Visits to a dermatologist are more likely to be associated with a procedure for NMSC, and there may be discrepancies in treatment patterns based on insurance type and sex.

View details for DOI 10.1111/dsu.12092

View details for Web of Science ID 000317018200010

View details for PubMedID 23331766

Abstract

Despite advancements in the diagnosis and treatment of peripheral vascular disease, major lower extremity amputations are still performed at high rates with non-negligible economic burdens. Peri-operative morbidity and mortality is greater for patients who receive an above knee amputation (AKA) compared to patients who receive a below knee amputation (BKA). We sought to further evaluate what variables affect whether a patient receives a BKA versus an AKA using the Nationwide Inpatient Sample (NIS).From 2005 to 2008, all adult AKA and BKA procedures were identified in the NIS. Patients with trauma and oncologic diagnoses were excluded from the analysis. Rates of AKA and BKA were evaluated according to patient demographics, co-morbidities, extent of pre-amputation vascular intervention, hospital setting/type, and geographic region. Multivariate logistic regression and 2-way ANOVA analyses was used to determine statistical significance.A total of 228,624 patients met inclusion criteria (126,076 BKA, 102,548 AKA). Patients who received an AKA were more likely to be female (p<0.0001), older (p<0.0001), have non-private insurance (p<0.0001), and have a higher Elixhauser Co-morbidity Index (p<0.0001). Patients who received a BKA were more likely to have hypertension, diabetes, and a spinal cord injury (p<0.0001). Less limb salvage vascular interventions were attempted in low-volume hospitals and in patients who subsequently received AKA (p<0.0001), while more limb salvage vascular interventions were performed at high-volume centers where more BKA procedures were performed (p<0.0001). The majority of major amputations were performed in southern states (46.4%), and more BKA procedures were performed in urban and teaching hospitals (p<0.0001).Using the NIS database we found important differences between patients who receive a BKA versus an AKA. These differences are broadly observed between patient demographics, race, and co-morbidities, as well as insurance type, geographic region, and hospital type. Our findings highlight the need for more aggressive surveillance and preventative care of at risk populations.

View details for DOI 10.1016/j.avsg.2013.11.008

View details for PubMedID 24365081

Abstract

Reintervention rates after repair of abdominal aortic aneurysm (AAA) are higher for endovascular repair (EVAR) than for open repair, mostly due to treatment for endoleaks, whereas open surgical operations for bowel obstruction and abdominal hernias are higher after open repair. However, readmission rates after EVAR or open repair for nonoperative conditions and complications that do not require an intervention are not well documented. We sought to determine reasons for all-cause readmissions within the first year after open repair and EVAR.Patients who underwent elective AAA repair in California during a 6-year period were identified from the Health Care and Utilization Project State Inpatient Database. All patients who had a readmission in California ?1 year of their index procedure were included for evaluation. Readmission rates and primary and secondary diagnoses associated with each readmission were analyzed and recorded.From 2003 to 2008, there were 15,736 operations for elective AAA repair, comprising 9356 EVARs (60%) and 6380 open repairs (40%). At 1 year postoperatively, the readmission rate was 52.1% after open repair and 55.4% after EVAR (P=.0003). The three most common principle diagnoses associated with readmission after any type of AAA repair were failure to thrive, cardiac issues, and infection. When stratified by repair type, patients who underwent open repair were more likely to be readmitted with primary diagnoses associated with failure to thrive, cardiac complications, and infection compared with EVAR (all P<.001). Those who underwent EVAR were more likely, however, to be readmitted with primary diagnoses of device-related complications (P=.05), cardiac complications, and infection.Total readmission rates within 1 year after elective AAA repair are greater after EVAR than after open repair. Reasons for readmission vary between the two cohorts but are related to the magnitude of open surgery after open repair, device issues after EVAR, and the usual cardiac and infectious complications after either intervention. Systems-based analysis of these causes of readmission can potentially improve patient expectations and care after elective aneurysm repair.

View details for DOI 10.1016/j.jvs.2012.07.005

View details for Web of Science ID 000312833800016

View details for PubMedID 23164606

Abstract

The study aimed to better define the epidemiology of idiopathic acute pancreatitis (IAP).We identified admissions with primary diagnosis of acute pancreatitis (AP) in Nationwide Inpatient Sample between 1998 and 2007. Idiopathic AP was defined as all cases after excluding International Classification of Diseases, Ninth Revision, codes for other causes of AP (including biliary, alcoholic, trauma, iatrogenic, hyperparathyroidism, hyperlipidemia, etc).Among the primary admissions for AP, 26.9% had biliary pancreatitis, 25.1% alcoholic, and 36.5% idiopathic. Idiopathic AP had estimated 81,8025 admissions with a mean hospitalization of 5.6 days. Patients with IAP accounted for almost half of the fatalities among the cases of AP (48.2%) and had a higher mortality rate than both patients with biliary pancreatitis and patients with alcoholic pancreatitis (1.9%, 1.5%, and 1.0%, respectively, P < 0.01). Forty-six percent of patients with biliary pancreatitis underwent cholecystectomy during the index hospitalization, compared with 0.42% of patients with IAP. Patients with IAP had a demographic distribution similar to that of patients with biliary AP (female predominant and older), which was distinct from patients with alcoholic pancreatitis (male predominant and younger). There was a gradual but steady decrease in the incidence of IAP, from 41% in 1998 to 30% in 2007.Despite improving diagnostics, IAP remains a common clinical problem with a significant mortality. Standardization of the clinical management of these patients warrants further investigation.

View details for DOI 10.1097/MPA.0b013e3182572d3a

View details for Web of Science ID 000312560200001

View details for PubMedID 22750972

Abstract

Improving quality of health care is a global priority. Before quality benchmarks are established, we first must understand rates of adverse events (AEs). This project assessed risk-adjusted rates of inpatient AEs for soft tissue reconstructive procedures.Patients receiving soft tissue reconstructive procedures from 2005 to 2010 were extracted from the Nationwide Inpatient Sample. Inpatient AEs were identified using patient safety indicators (PSIs), established measures developed by Agency for Healthcare Research and Quality.We identified 409,991 patients with soft tissue reconstruction and 16,635 (4.06%) had a PSI during their hospital stay. Patient safety indicators were associated with increased risk-adjusted mortality, longer length of stay, and decreased routine disposition (P < 0.01). Patient characteristics associated with a higher risk-adjusted rate per 1000 patients at risk included older age, men, nonwhite, and public payer (P < 0.05). Overall, plastic surgery patients had significantly lower risk-adjusted rate compared to other surgical inpatients for all events evaluated except for failure to rescue and postoperative hemorrhage or hematoma, which were not statistically different. Risk-adjusted rates of hematoma hemorrhage were significantly higher in patients receiving size-reduction surgery, and these rates were further accentuated when broken down by sex and payer.In general, plastic surgery patients had lower rates of in-hospital AEs than other surgical disciplines, but PSIs were not uncommon. With the establishment of national basal PSI rates in plastic surgery patients, benchmarks can be devised and target areas for quality improvement efforts identified. Further prospective studies should be designed to elucidate the drivers of AEs identified in this population.

View details for DOI 10.1097/SAP.0b013e318297791e

View details for PubMedID 24108144

Abstract

Severe obesity remains the leading public health concern of the industrialized world, with bariatric surgery as the only current effective enduring treatment. In addition to gastric bypass, gastric banding and sleeve gastrectomy have emerged as viable treatment options for the severely obese. Occasionally, poor postoperative psychological adjustment has been reported. It has been previously demonstrated that breath alcohol content (BAC) levels and time to sober were increased in postoperative gastric bypass patients. The aim of this study was to examine whether alcohol metabolism in patients undergoing restrictive-type bariatric procedures is also altered.Nine patients undergoing laparoscopic adjustable gastric banding (LAGB) and 7 patients undergoing laparoscopic sleeve gastrectomy (LSG) were recruited. Preoperatively, 3-month and 6-month BAC and time to sober were measured after administration of 5 ounces of red wine. In addition, participants were asked to complete a questionnaire of drinking habits.The 16 total participants achieved a mean 44.7% 6-month excess weight loss. There were no significant changes in peak BAC or time to sober from preoperative levels (0.033%, 67.8 min, respectively) to 3 months (0.032%, 77.1 min, respectively, p = 0.421) or 6 months (0.035%, 81.2 min, respectively, p = 0.198).Patients undergoing LAGB and LSG do not share the same altered alcohol metabolism as seen in gastric bypass patients. However, all bariatric surgery patients should be counseled regarding alcohol use.

View details for DOI 10.1016/j.jamcollsurg.2012.06.008

View details for Web of Science ID 000308910300003

View details for PubMedID 22770864

Abstract

Ruptured abdominal aortic aneurysm (rAAA) is a critically time-sensitive condition with outcomes dependent on rapid diagnosis and definitive treatment. Emergency department (ED) death reflects the hemodynamic stability of the patient upon arrival and the ability to mobilize resources before hemodynamic stability is lost. The goals of this study were to determine the incidence and predictors of ED death for patients presenting to EDs with rAAAs.Data for patients presenting with International Classification of Disease, 9th Revision, Clinical Modification codes for rAAA from 2006 to 2008 were extracted from discharge data using the Nationwide Emergency Department Sample (NEDS), Healthcare Cost and Utilization Project, and Agency for Healthcare Research and Quality. The NEDS is the largest stratified weighted sample of US hospital-based ED visits with links to inpatient files. We compared those transferred to those admitted and treated. Sample weights were applied to produce nationally representative estimates. Patient and hospital factors associated with transfer were identified using multivariate logistic regression. These factors were then analyzed for a relationship with ED deaths.A total of 18,363 patients were evaluated for rAAAs. Of these, 7% (1201) died in the ED, 6% (1160) were admitted and died without a procedure, 42% (7731) were admitted and died after repair, and 41% (7479) were admitted, treated, and survived. Transfers accounted for 4% (793) of all ED visits for rAAAs. ED death was more likely for patients seen in nonmetropolitan hospitals (12.7%) vs metropolitan nonteaching (7.0%) or metropolitan teaching hospitals (4.5%; P < .0001). Compared with other regions, the West had a higher ED mortality rate (9.6% vs 5.1%-6.9%; P = .0038). On multivariate analysis, ED death was associated with hospital groups exhibiting both high and low transfer rates.ED death remains a significant cause for mortality for rAAAs and varies by hospital type, rural/urban location, and geographic region. Both delays in ED arrival and delays in providing definitive care may contribute to increased ED death rates, suggesting that improved regional systems of care may improve survival after rAAA.

View details for DOI 10.1016/j.jvs.2012.02.025

View details for Web of Science ID 000308085500010

View details for PubMedID 22560234

Abstract

Pathologic response to preoperative chemotherapy for colorectal liver metastases (CLM) is associated with survival after hepatectomy. Histologically, dominant response patterns include fibrosis, necrosis and/or acellular mucin, but some of these changes can appear without previous chemotherapy and their individual correlation with outcome is unknown.Pathology slides from patients who underwent CLM resection (irrespective of preoperative chemotherapy status) were rereviewed by a blinded pathologist. Pathologic response was recorded as the summation of percentage necrosis, fibrosis and acellular mucin. Associations between pathologic response, its components, preoperative chemotherapy, and survival were analyzed.Pathology slides were rereviewed in 366 patients undergoing CLM resection from 2003 to 2007. Preoperative chemotherapy was administered in 249 (68 %) patients, who, when compared to no preoperative chemotherapy patients, had higher rates of overall pathologic response (57 vs. 46 %, P < .01), fibrosis (21 vs. 12 %, P < .01) and acellular mucin (6 vs. 3 %, P = .05) but similar rates of necrosis (30 vs. 31 %, P = .30). In patients receiving preoperative chemotherapy, overall pathologic response ? 75 % (5 year, 83 vs. 47 %, P < .01) and fibrosis ? 40 % (5 year, 87 vs. 51 %, P < .01) independently correlated with disease-specific survival after hepatectomy. Preoperative hepatic artery infusion chemotherapy (P = .04) and bevacizumab (P = .05) were marginally associated with overall pathologic response and fibrosis, respectively.Fibrosis is the predominant chemotherapy-related pathologic alteration driving the association of treatment response with survival after CLM resection. Necrosis in CLM is not related to chemotherapy or outcome.

View details for DOI 10.1245/s10434-012-2335-1

View details for Web of Science ID 000308357100005

View details for PubMedID 22476753

Abstract

Obesity and its consequences are a major health concern. There are conflicting reports regarding utilization of preventive health-care services among obese patients. Our objective was to determine whether obese patients receive the same preventive care as normal weight patients. Weighted patient clinic visit data from the National Ambulatory Medical Care Survey (NAMCS) were analyzed for all adult patient visits with height/weight data (N = 866,415,856) from 2005 to 2007. Preventive care practice patterns were compared among different weight groups of normal, obese, and morbidly obese. Obese patients received the least number of preventive exams with a clear gradient present by weight. Obese patients were significantly less likely to receive cancer screening including breast examination (normal weight, reference, obese, odds ratio (OR), 0.8), mammogram (obese OR, 0.7), pap smear (obese OR, 0.7), pelvic exam (obese OR, 0.8), and rectal exam (obese OR, 0.7). The obese population also received less tobacco (obese OR, 0.7) and injury prevention education (obese OR, 0.7), yet significantly more diet, exercise, and weight reduction education. Significant differences in clinic practice patterns relative to normal weight patients were also evident with more physician referral (obese OR, 1.2) and less likely to see physician at the index clinic visit (obese OR, 0.8) and less likely to receive psychotherapy referral (obese OR, 0.6). Significant gaps in preventive care exist for the obese including cancer screening, tobacco cessation and injury prevention counseling, and psychological referral. Although obese patients received more weight-related education, this emphasis may have the consequence of de-emphasizing other needed preventive health measures.

View details for DOI 10.1038/oby.2011.258

View details for Web of Science ID 000306920900013

View details for PubMedID 21818146

Abstract

To determine national outcome differences between laparoscopic Roux-en-Y gastric bypass (LRYGB) and open Roux-en-Y gastric bypass (ORYGB).Retrospective cohort study.The Nationwide Inpatient Sample.Patients undergoing ORYGB and LRYGB.Outcome measures were number of procedures performed, patient and hospital characteristics, patient complications, mortality, length of stay, resource use, and Agency for Healthcare Research and Quality Patient Safety Indicators. Both demographic and outcomes variables were compared by either t test or ?2 analysis, with regression analysis adjusting for confounding variables.The ORYGB and LRYGB cohorts consisted of 41 094 and 115 177 cases, respectively. From 2005 to 2007, LRYGB was more commonly performed than ORYGB (72% vs 28%; P < .001) and at high-volume hospitals (69% vs 61%; P < .001). A higher percentage of ORYGB compared with LRYGB patients were Medicare (9.3% vs 7.1%) and Medicaid (10.4% vs 5.9%; P < .01) beneficiaries. More ORYGB patients compared with LRYGB patients were discharged with nonroutine dispositions (7.7% vs 2.4%; P = .005), died (0.2% vs 0.1%; P < .001), and had 1 or more complications (18.7% vs 12.3%; P < .001). All Patient Safety Indicator rates were higher for ORYGB. Patients who had ORYGB compared with LRYGB also had longer median lengths of stay (3.5 vs 2.4 days; P < .001) and higher total charges ($35 018 vs $32 671; P < .001). Patients who had LRYGB had a lower odds ratio than patients who had ORYGB for both mortality (odds ratio, 0.54; P < .001) and having 1 or more complications (odds ratio, 0.66; P < .001) even after adjusting for confounding variables.In this population-based study, LRYGB provided greater safety than ORYGB even after adjusting for patient-level socioeconomic and comorbidity differences.

View details for Web of Science ID 000305428500014

View details for PubMedID 22786543

Abstract

Obese men have lower serum levels of testosterone, dehydroepiandrosterone (DHEA) and prostate-specific antigen (PSA), but an increased risk of dying from prostate cancer. The aim of this study was to examine the effect of surgically induced weight loss on serum testosterone, DHEA and PSA levels in obese men.Consecutive men undergoing Roux-en-Y gastric bypass (RYGB) participated in a prospective, longitudinal study. Main outcomes were changes were body mass index (BMI), percentage excess weight loss, serum levels of testosterone, DHEA and PSA, PSA mass and plasma volume, measured before operation and 3, 6 and 12 months later.In 64 patients, mean BMI fell from 48.2 kg/m(2) before operation to 39.2, 35.6 and 32.4 kg/m(2) at 3, 6 and 12 months after RYGB. Testosterone levels rose significantly from 259 ng/dl to 386, 452 and 520 ng/dl respectively. Serum PSA levels increased significantly from 0.51 ng/ml to 0.67 ng/ml at 12 months. There were no significant changes in DHEA or PSA mass.RYGB normalizes the serum testosterone level. PSA levels increase with weight loss and may be inversely correlated with changes in plasma volume, indicating that PSA levels may be artificially low in obese men owing to haemodilution.

View details for DOI 10.1002/bjs.8693

View details for Web of Science ID 000303150700016

View details for PubMedID 22302466

Abstract

Patient safety is a national priority. Patient Safety Indicators (PSIs) monitor potential adverse events during hospital stays. Surgical specialty PSI benchmarks do not exist, and are needed to account for differences in the range of procedures performed, reasons for the procedure, and differences in patient characteristics. A comprehensive profile of adverse events in vascular surgery was created.The Nationwide Inpatient Sample was queried for 8 vascular procedures using ICD-9-CM codes from 2005 to 2009. Factors associated with PSI development were evaluated in univariate and multivariate analyses.A total of 1,412,703 patients underwent a vascular procedure and a PSI developed in 5.2%. PSIs were more frequent in female, nonwhite patients with public payers (p < 0.01). Patients at mid and low-volume hospitals had greater odds of developing a PSI (odds ratio [OR] = 1.17; 95% CI, 1.10-1.23 and OR = 1.69; 95% CI, 1.53-1.87). Amputations had highest PSI risk-adjusted rate and carotid endarterectomy and endovascular abdominal aortic aneurysm repair had lower risk-adjusted rate (p < 0.0001). PSI risk-adjusted rate increased linearly by severity of patient indication: claudicants (OR = 0.40; 95% CI, 0.35-0.46), rest pain patients (OR = 0.78; 95% CI, 0.69-0.90), ulcer (OR = 1.20; 95% CI, 1.07-1.34), and gangrene patients (OR = 1.85; 95% CI, 1.66-2.06).Patient safety events in vascular surgery were high and varied by procedure, with amputations and open abdominal aortic aneurysm repair having considerably more potential adverse events. PSIs were associated with black race, public payer, and procedure indication. It is important to note the overall higher rates of PSIs occurring in vascular patients and to adjust benchmarks for this surgical specialty appropriately.

View details for DOI 10.1016/j.jamcollsurg.2012.01.045

View details for Web of Science ID 000303724200009

View details for PubMedID 22425449

Abstract

To examine the relationship between hospital volume and in-hospital adverse events.Patient safety indicator (PSI) was used to identify hospital-acquired adverse events in the Nationwide Inpatient Sample database in abdominal aortic aneurysm, coronary artery bypass graft, and Roux-en-Y gastric bypass from 2005 to 2008.In this observational study, volume thresholds were defined by mean year-specific terciles. PSI risk-adjusted rates were analyzed by volume tercile for each procedure.Overall, hospital volume was inversely related to preventable adverse events. High-volume hospitals had significantly lower risk-adjusted PSI rates compared to lower volume hospitals (p < .05).These data support the relationship between hospital volume and quality health care delivery in select surgical cases. This study highlights differences between hospital volume and risk-adjusted PSI rates for three common surgical procedures and highlights areas of focus for future studies to identify pathways to reduce hospital-acquired events.

View details for DOI 10.1111/j.1475-6773.2011.01310.x

View details for Web of Science ID 000301229300012

View details for PubMedID 22091561

Abstract

Previous studies in other medical specialties have shown a significant percentage of publications represented in residency applications are not actually published. A comprehensive evaluation of applicants to plastic surgery residency over an extended period has not been previously reported in the literature. The purpose of our study was to determine the incidence of misrepresented or "phantom" publications in plastic surgery residency applicants and to identify possible predisposing characteristics.We used the Electronic Residency Application Services database to our plastic surgery residency program during a 4-year period from 2006 to 2009. Applicant demographic information and listed citations were extracted. Peer-reviewed journal article citations were verified using robust methods including PubMed, Institute for Scientific Information (ISI) Web of Knowledge, and Google. Unverifiable articles were categorized as phantom publications and then evaluated with respect to applicant demographic information and characteristics.During the 4-year study period, there were 804 applications (average, 201 applicants per year). There was a total of 4725 publications listed; of which, 1975 had been categorized as peer-reviewed journal articles. Two hundred seventy-six (14%) of peer-reviewed publications could not be verified and were categorized as phantom publications. There was an overall significant positive trend in percentage of phantom publications during the 4 application years (P = 0.005). A positive predictive factor for having phantom publications was being a foreign medical graduate (P = 0.02). A negative predictive factor for phantom publications was being a female applicant (P = 0.03). There also appeared to be a positive correlation with the number of publications listed and likelihood of phantom publications.Among plastic surgery residency applicants, we found a significant percentage of unverifiable publications. There are several possible explanations for our findings, which include the fact that plastic surgery is a highly sought-after specialty and applicants may feel the need to appear competitive to residency programs. Publications are an important aspect of the residency selection process and factors into applicant ranking, but our study suggests publications listed in plastic surgery residency applications may not necessarily be an accurate representation of actual published articles. Program directors and faculty are advised to scrutinize listed publications carefully when evaluating applicants.

View details for DOI 10.1097/SAP.0b013e31823d2c4e

View details for Web of Science ID 000301800600015

View details for PubMedID 22421486

Abstract

Emphasis has been placed on quality and patient safety in medicine; however, little is known about whether quality over time has actually improved in areas such as patient safety indicators (PSIs).To determine whether national trends for hospital PSIs have improved from 1998 to 2007.Using PSI criteria from the Agency for Healthcare Research and Quality, PSIs were identified in the Nationwide Inpatient Sample (NIS) for all eligible inpatient admissions between 1998 and 2007. Joinpoint regression was used to estimate annual percentage changes (APCs) for PSIs.Annual percent change for PSIs.From 1998 to 2007, 7.6 million PSI events occurred for over 69 million hospitalizations. A total of 14 PSIs showed statistically significant trends. Seven PSIs had increasing APC: postoperative pulmonary embolism or deep vein thrombosis (8.94), postoperative physiological or metabolic derangement (7.67), postoperative sepsis (7.17), selected infections due to medical care (4.05), decubitus ulcer (3.05), accidental puncture or laceration (2.64), and postoperative respiratory failure (1.46). Seven PSIs showed decreasing APCs: birth trauma injury to neonate (-17.79), failure to rescue (-6.05), postoperative hip fracture (-5.86), obstetric trauma-vaginal without instrument (-5.69), obstetric trauma-vaginal with instrument (-4.11), iatrogenic pneumothorax (-2.5), and postoperative wound dehiscence (-1.8).This is the first study to establish national trends of PSIs during the past decade indicating areas for potential quality improvement prioritization. While many factors influence these trends, the results indicate opportunities for either emulation or elimination of current patient safety trends.

View details for DOI 10.1111/j.1475-6773.2011.01361.x

View details for Web of Science ID 000299041600007

View details for PubMedID 22150789

Abstract

Objective :? Our study aimed to use national data to assess the perioperative outcomes of craniosynostosis surgical repair. Design :? Data were obtained from the Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project Kids Inpatient Database from 1997, 2000, 2003, and 2006. Setting :? Community hospitals in the United States. Patients :? The cohort was identified using the ICD-9-CM procedure codes for craniosynostosis surgical repair (2.01, 2.03, 2.04, 2.06). Main Outcome Measures(s) :? We determined patient and hospital characteristics. We clustered patients by age group (<7 months, 7 to 12 months, 1 to 3 years) and assessed mortality, comorbidities, mean length of stay (LOS), and total charge. We performed logistic regression with our dependent variable being longer average hospital stay: LOS >4.2 days. Results :? We found 3426 patients. Average age at the time of surgery was 181 days (SD 84). Average length of stay was 4.2 days. The majority of the patients were boys (66%), white (71%), and insured (93%). Nearly all patients underwent surgery in a teaching hospital (98%) in urban centers (99%). Approximately 10% of patients experienced an acute complication, most commonly hemorrhages or hematomas and airway or respiratory failure. Patients ages 1 to 3 years had the highest rates of comorbidities and a longer LOS. Mortality rate was <1%. Conclusions :? Craniosynostosis surgery is safe with low rates of mortality and acute complications. LOS >4.2 appears to be associated more with comorbidities than with complications. Higher rates of comorbidities and LOS >4.2 days for patients age 1 to 3 years warrant addition research to assess potential barriers to care.

View details for PubMedID 23030675

View details for Web of Science ID 000298256900020

Abstract

Bariatric surgery is an effective treatment for morbid obesity, which is increasingly recognized as a familial disease. Healthy behavior transmission may be enhanced by family relationships.To determine changes in weight and healthy behavior in patients who underwent Roux-en-Y gastric bypass surgery and their family members.Prospective, longitudinal, and multidimensional health assessment before and 1 year after index Roux-en-Y gastric bypass surgery.An academic bariatric center of excellence, from January 1, 2007, through December 31, 2009.Eighty-five participants (35 patients, 35 adult family members, and 15 children <18 years old).Roux-en-Y gastric bypass surgery and associated dietary and lifestyle counseling.Weight and expected body mass index (calculated as weight in kilograms divided by height in meters squared). Secondary outcomes were waist circumference, quality of life (36-Item Short Form or Pediatric Quality of Life Inventory), healthy behaviors, eating behaviors, and activity levels.Participants were grouped by relationship to patient for analysis with paired 2-sample t tests. Before the operation, 60% of adult family members and 73% of children of patients undergoing Roux-en-Y gastric bypass surgery were obese. At 12 months after the operation, significant weight loss was observed in obese adult family members (from 234 to 226 lb; P = .01). There was a trend for obese children to have a lower body mass index than expected for their growth curve (31.2 expected vs 29.6 observed; P = .07). Family members increased their daily activity levels (adults, from 8 to 17 metabolic equivalent task-hours, P = .005; and children, from 13 to 22, P = .04). Adult family members also had improved eating habits with less uncontrollable eating (from 35 to 28; P = .01), emotional eating (from 36 to 28; P = .04), and alcohol consumption (from 11 drinks per month to 1 drink per month; P = .009).Gastric bypass surgery may render an additional benefit of weight loss and improved healthy behavior for bariatric patients' family members.

View details for Web of Science ID 000295942300018

View details for PubMedID 22006878

Abstract

An important facet of laparoscopic surgery is its psychomotor component. As this aspect of surgery gains attention, lessons from other psychomotor-intense fields such as athletics have led to an investigation of the benefits of "warming up" prior to entering the operating room. Practical implementation of established methods of warm-up is hampered by a reliance on special equipment and instrumentations that are not readily available. In light of emerging evidence of translatability between video-game play and operative performance, we sought to find if laparoscopic task performance improved after warming up on a mobile device balance game.Laparoscopic novices were randomized into either the intervention group (n = 20) or the control group (n = 20). The intervention group played a mobile device balance game for 10 min while the control group did no warm-up whatsoever. Assessment was performed using two tasks on the ProMIS laparoscopic simulation system: "object positioning" (where small beads are transferred between four cups) and "tissue manipulation" (where pieces of plastic are stretched over pegs). Metrics measured were time to task completion, path length, smoothness, hand dominance, and errors.The intervention group made fewer errors: object positioning task 0.20 versus 0.70, P = 0.01, tissue manipulation task 0.15 versus 0.55, P = 0.05, total errors 0.35 versus 1.25, P = 0.002. The two groups performed similarly on the other metrics.Warm-up using a mobile device balance game decreases errors on basic tasks performed on a laparoscopic surgery simulator, suggesting a practical way to warm-up prior to cases in the operating room.

View details for DOI 10.1016/j.jss.2011.03.015

View details for Web of Science ID 000295128600013

View details for PubMedID 21529831

View details for Web of Science ID 000293814400076

View details for DOI 10.1097/FPC.0b013e32833ffb56

View details for Web of Science ID 000291633300011

View details for PubMedID 21048526

Abstract

The decision to proceed with digital replantation in the elderly can be challenging. In addition to success of the replanted part, perioperative morbidity and mortality must be considered. The purpose of this study was to compare adverse events in patients less than 65 years of age compared with those 65 years and older after digital replantation. We hypothesize that there is an increased incidence of mortality and sentinel adverse events in patients aged 65 and older.We obtained data from the Nationwide Inpatient Sample over a 10-year period from 1998 to 2007. Replantation was identified using International Classification of Diseases-9 procedure codes for finger and thumb reattachment (84.21 and 84.22). Adverse events were identified using Patient Safety Indicators (PSI) to identify adverse events occurring during hospitalization. We used the Charlson index to study medical comorbidities and bivariate statistics.During the study period 15,413 finger and thumb replantations were performed in the United States, with 616 performed on patients age 65 and older. The overall in-hospital mortality was 0.04% with no statistical difference when factoring age. For the entire group, the percentage of PSI was 0.6%, the most common being postoperative deep venous thrombosis and pulmonary embolus. Overall, there was no difference in PSI between the 2 groups. The older group had a higher rate of transfusion, 4% versus 8% (p < .05) and were more likely to have a nonroutine disposition (ie, nursing home) (p < .001). We found no correlation between the Charlson index and PSI.This study found no difference in sentinel perioperative complications or mortality when comparing replantation patients under 65 years of age and those age 65 and older. Age alone should not be an absolute contraindication to finger replantation. Instead, the patient's functional demands, type of injury, general state of health, and rehabilitative potential should drive the decision of whether to proceed with replantation.

View details for DOI 10.1016/j.jhsa.2011.01.031

View details for Web of Science ID 000290185700017

Abstract

Subclinical microemboli documented on diffusion-weighted magnetic resonance imaging (DWI) are common following carotid artery stenting (CAS) procedures despite absence of neurological symptoms. This study was to evaluate risk factors predictive of microemboli in patients undergoing protected CAS with a distal embolic protection device. All CAS patients who received pre- and postprocedural magnetic resonance imaging (MRI) evaluations for carotid interventions at a single academic institution from July 2004 to December 2008 were examined. Microemboli were defined by new hyperintensities on postoperative DWI with corresponding decreased diffusion. Risk factors including patient demographics, medical comorbidities, clinical symptoms, lesion morphologies, and perioperative information were examined, and logistic regression analyses were utilized to determine predictors of CAS-related microemboli. A total of 204 patients underwent carotid interventions (76 CAS and 128 carotid endarterectomies) during the study period; 167 of them, including 67 CAS patients, received both preoperative and postoperative MRIs. Among those who underwent protected CAS, the incidence of microemboli was 46.3% despite a relative low incidence of associated neurological symptoms (2.9%). Univariate and multivariate regression analyses showed that date of procedure (odds ratio [OR] 30.6 and p?=?0.019) and preoperative transient ischemic attack symptoms (OR 9.24 and p?=?0.009) were independent predictors of developing postoperative changes on DWI in the ipsilateral hemisphere, and age >76 years was predictive of having new lesions on DWI in the contralateral hemisphere (OR 6.11 and p?=?0.026). Our study underscores that certain risk factors are significantly associated with CAS-related microemboli and that physician experience and patient selection are essential in improving outcome of CAS procedures.

View details for DOI 10.1055/s-0031-1272546

View details for PubMedID 22532767

Abstract

Severe obesity remains the leading public health crisis of the industrialized world, with bariatric surgery the only effective and enduring treatment. Poor psychological adjustment has been occasionally reported postoperatively. In addition, evidence suggests that patients can metabolize alcohol differently after gastric bypass.Preoperatively and at 3 and 6 months postoperatively, 19 Roux-en-Y gastric bypass (RYGB) patients' breath alcohol content (BAC) was measured every 5 minutes after drinking 5 oz red wine to determine peak BAC and time until sober in a case-crossover design preoperatively and at 6 months postoperatively.Patients reported symptoms experienced when intoxicated and answered a questionnaire of drinking habits. The peak BAC in patients after RYGB was considerably higher at 3 months (0.059%) and 6 months (0.088%) postoperatively than matched preoperative levels (0.024%). Patients also took considerably more time to return to sober at 3 months (61 minutes) and 6 months (88 minutes) than preoperatively (49 minutes). Postoperative intoxication was associated with lower levels of diaphoresis, flushing, and hyperactivity and higher levels of dizziness, warmth, and double vision. Postoperative patients reported drinking considerably less alcohol, fewer preferred beer, and more preferred wine than before surgery.This is the first study to match preoperative and postoperative alcohol metabolism in gastric bypass patients. Post-RYGB patients have much higher peak BAC after ingesting alcohol and require more time to become sober. Patients who drink alcohol after gastric bypass surgery should exercise caution.

View details for DOI 10.1016/j.jamcollsurg.2010.09.020

View details for Web of Science ID 000287466200010

View details for PubMedID 21183366

Abstract

To determine the incidence of neonatal endogenous endophthalmitis in the United States between 1998 and 2006 and to identify associated risk factors.Retrospective cohort study.We used the Nationwide Inpatient Sample database, a 20% representative sample of all hospital discharges in the United States, to help refine our understanding of this condition. International Classification of Diseases, ninth edition, codes for endophthalmitis, sepsis, and suspected endophthalmitis risk factors in hospitalized infants and neonates were searched in the database and were tracked over time. The main outcome measure was incidence of neonatal endophthalmitis over the study period.Of 3.64 million live births in 1998, 317 newborns were identified with endophthalmitis (8.71 cases per 100 000 live births). Of 4.14 million live births in 2006, only 183 newborns were identified with endophthalmitis (4.42 cases per 100 000 live births) by comparison. The incidence of endophthalmitis decreased at a rate of 6% per year (P = .01130) between 1998 and 2006. Neonates with endophthalmitis were more likely to have systemic bacteremia (odds ratio, 21.114; P < .0001), Candidemia (odds ratio, 2.356; P < .0001), a birth weight of less than 1500 g (odds ratio, 1.215; P < .0001), and retinopathy of prematurity (odds ratio, 2.052; P < .0001).We objectively validated the commonly held belief that Candidemia, bacteremia, retinopathy of prematurity, and low birth weight are significant risk factors for endophthalmitis development in infants, which seems to have had a decreasing incidence in recent years.

View details for DOI 10.1016/j.ajo.2010.07.008

View details for Web of Science ID 000286081200011

View details for PubMedID 20970776

View details for Web of Science ID 000283811500684

Abstract

The veteran population is routinely screened for post-traumatic stress disorder (PTSD). The prevalence of obesity in this population continues to increase. We examined whether weight loss outcomes in veterans with PTSD is comparable to results in veterans who do not suffer from PTSD, after gastric bypass. We also examined the effect of bariatric surgery on PTSD symptoms.This retrospective review of prospective data compares veterans with and without PTSD who underwent laparoscopic gastric bypass. Differences between the means of age, initial BMI, and percent excess weight loss were compared between the groups using a Student's t test. Pearson's chi(2) was used to evaluate the relationship between a diagnosis of PTSD, major depressive disorder (MDD), and other Axis I psychiatric disorders. A similar analysis was done to assess for a relationship between PTSD and obesity-related comorbidities, including diabetes mellitus (DM), hypertension (HTN), hyperlipidemia, and GERD.We identified 24 patients who had gastric bypass and a diagnosis of PTSD before surgery and compared them to those without PTSD. Both groups had a similar mean age and initial BMI. There was no significant difference between the percent excess weight lost after 1 year follow-up between the PTSD group (66%) and the non-PTSD group (72%) (p = 0.102). In assessing comorbid conditions, we found a significant association between the diagnosis of PTSD and MDD (p = 0.002), PTSD and other Axis I disorders (p = 0.004), and PTSD and GERD (p = 0.002). However, we saw no significant association between PTSD and DM (p = 0.977), HTN (p = 0.332), and obstructive sleep apnea (OSA) (p = 0.676). The severity of PTSD symptoms fluctuated in the postoperative period.Veterans with PTSD have comparable weight loss to those without PTSD after gastric bypass. In addition, surgery does not seem to have an adverse effect on PTSD symptoms, although PTSD symptomatology tends to fluctuate over time. Further study in this patient population is warranted.

View details for DOI 10.1007/s00464-009-0866-8

View details for Web of Science ID 000279488400015

View details for PubMedID 20063014

Abstract

Surgical robotics has been promoted as an enabling technology. This study tests the hypothesis that use of the robotic surgical system can significantly improve technical ability by comparing the performance of both experts and novices on a complex laparoscopic task and a robotically assisted task.Laparoscopic experts (LE) with substantial laparoscopic and robotic experience (n = 9) and laparoscopic novices (LN) (n = 20) without any robotic experience performed sequentially 10 trials of a suturing task using either robotic or standard laparoscopic instrumentation fitted to the ProMIS surgical simulator. Objective performance metrics provided by ProMIS (total task time, instrument pathlength, and smoothness) and an assessment of learning curves were analyzed.Compared with LNs, the LEs demonstrated significantly better performance on all assessment measures. Within the LE group, there was no difference in smoothness (328 +/- 159 vs 355 +/- 174; P = .09) between robot-assisted and standard laparoscopic tasks. An improvement was noted in total task time (113 +/- 41 vs 132 +/- 55 sec; P < .05) and instrument pathlengths (371 +/- 163 vs 645 +/- 269 cm; P < .05) when using the robot. This advantage in terms of total task time, however, was lost among the LEs by the last 3 trials (114 +/- 40 vs 118 +/- 49 s; P = .84), while instrument pathlength remained better consistently throughout all the trials. For the LNs, performance was significantly better in the robotic trials on all 3 measures throughout all the trials.The ProMIS surgical simulator was able to distinguish between skill levels (expert versus novice) on robotic suturing tasks, suggesting that the ProMIS is a valid tool for measuring skill in robot-assisted surgery. For all the ProMIS metrics, novices demonstrated consistently better performance on a suturing task using robotics as compared to a standard laparoscopic setup. This effect was less evident for experts who demonstrated improvements only in their economy of movement (pathlength), but not in the speed or smoothness of performance. Robotics eliminated the early learning curve for novices, which was present when they used standard laparoscopic tools. Overall, this study suggests that, when performing complex tasks such as knot tying, surgical robotics is most useful for inexperienced laparoscopists who experience an early and persistent enabling effect. For experts, robotics is most useful for improving economy of motion, which may have implications for the highly complex procedures in limited workspaces (eg, prostatectomy).

View details for DOI 10.1016/j.surg.2009.11.002

View details for Web of Science ID 000278532300011

View details for PubMedID 20045162

Abstract

Coronary artery disease (CAD) is the leading cause of death in the industrialized world with obesity as a leading preventable risk factor. Roux-en-Y gastric bypass (RYGB) and laparoscopic adjustable gastric banding (LAGB) have been shown to improve certain biochemical cardiovascular risk factors (BCRFs) at 1 year post-op, however no study has directly compared the 12-month BCRF improvements of RYGB vs. LAGB.At a single academic institution (2004-2009), we measured BCRF in 838 consecutive bariatric patients (765 RYGB, 73 LAGB) pre-operatively and at 12 months post-operatively. BCRF included total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides (Trig), Trig/HDL ratio, lipoprotein(a) (Lp(a)), homocysteine (HmC), high sensitivity C-reactive protein (hs-CRP), fasting insulin (FI), and hemoglobin A1C (Hgb A1C). Pre-op and 12-month post-op values were compared by a paired t test of equal variance.At 12 months post-op, RYGB patients had lost 77% of their excess weight and had significant improvements in TC, LDL, HDL, Trig, Trig/HDL, HmC, hs-CRP, FI, and Hgb A1C. LAGB patients lost 47.6% of their excess weight and had significant improvements in Trig, Trig/HDL, HmC, hs-CRP, and Hgb A1C. Having RYGB instead of LAGB was predictive of significantly greater improvements in TC at 12 months post-operatively.In this study, both RYGB and LAGB demonstrated significant weight loss and improvements in BCRF at 12 months post-op. RYGB produced significant improvements in a greater number of BCRFs and in some instances the 12-month post-op BCRF values were significantly lower risk in RYGB vs. LAGB patients.

View details for DOI 10.1007/s11695-010-0088-0

View details for Web of Science ID 000276470700007

View details for PubMedID 20186576

Abstract

DNA amplifications, leading to the overexpression of oncogenes, are a cardinal feature of lung cancer and directly contribute to its pathogenesis. To uncover such novel alterations, we performed an array-based comparative genomic hybridization survey of 128 non-small-cell lung cancer cell lines and tumors. Prominent among our findings, we identified recurrent high-level amplification at cytoband 22q11.21 in 3% of lung cancer specimens, with another 11% of specimens exhibiting low-level gain spanning that locus. The 22q11.21 amplicon core contained eight named genes, only four of which were overexpressed (by transcript profiling) when amplified. Among these, CRKL encodes an adapter protein functioning in signal transduction, best known as a substrate of the BCR-ABL kinase in chronic myelogenous leukemia. RNA-interference-mediated knockdown of CRKL in lung cancer cell lines with (but not without) amplification led to significantly decreased cell proliferation, cell-cycle progression, cell survival, and cell motility and invasion. In addition, overexpression of CRKL in immortalized human bronchial epithelial cells led to enhanced growth factor-independent cell growth. Our findings indicate that amplification and resultant overexpression of CRKL contribute to diverse oncogenic phenotypes in lung cancer, with implications for targeted therapy, and highlight a role of adapter proteins as primary genetic drivers of tumorigenesis.

View details for DOI 10.1038/onc.2009.437

View details for Web of Science ID 000275392400002

View details for PubMedID 19966867

View details for Web of Science ID 000279279800020

Abstract

Subclinical microemboli on diffusion-weighted magnetic resonance imaging (DWI) have been identified immediately following carotid revascularization procedures, but the clinical significance and long-term effects are largely unknown. The purpose of this study was to evaluate long-term radiographic outcomes of these DWI lesions.Patients who underwent perioperative magnetic resonance imaging (MRI) evaluations for carotid interventions at a single institution from July 2004 to December 2008 were evaluated, particularly those who had additional follow-up MRI. DWI with apparent diffusion coefficient (ADC), fluid-attenuated inversion recovery (FLAIR), and T2-weighted MRI images were compared to determine long-term effect of microemboli.One-hundred sixty-eight consecutive patients (68 carotid artery stenting [CAS] and 100 carotid endarterectomy [CEA]) who received perioperative MRI were included. All CAS were performed with an embolic protection device. The incidence of microemboli was significantly higher in the CAS group than the CEA group (46.3% and 12%, respectively, P < .05) despite a relative low incidence of procedure-associated neurologic symptoms in both groups (2.9% vs 2%). Thirty patients (16 CAS and 14 CEA) who had follow-up MRI were further analyzed and a total of 50 postoperative DWI lesions (mean size 46.57 mm(2); range 16 to 128 mm(2)) were identified among them. During a mean MRI follow-up of 10 months (range, 2 to 23 months), residual MRI abnormalities were only identified in DWI lesions larger than 60 mm(2) on postoperative MRI and on postoperative FLAIR images (n = 5, P < .001). The CEA group had fewer but larger ipsilateral distributed emboli (total 12 lesions, mean 79 mm(2)) compared with the CAS group (total 38 lesions, mean 27.5 mm(2), P < .05).The majority of microemboli do not have long-term radiographic sequelae. Size and hyperintensity on postoperative FLAIR are predictive of residual brain structure abnormality, and further neurocognitive evaluations are warranted.

View details for DOI 10.1016/j.jvs.2009.07.105

View details for Web of Science ID 000272860900010

View details for PubMedID 19837533

View details for Web of Science ID 000271237800075

Abstract

To determine the incidence of retinopathy of prematurity (ROP) based on a national database and to identify baseline characteristics, demographic information, comorbidities, and surgical interventions.Retrospective study based on the National Inpatient Sample from 1997 through 2005.The National Inpatient Sample was queried for all newborn infants with and without ROP. Multivariate logistic regression was used to predict risk factors for ROP.Thirty-four million live births were recorded during the study period. The total ROP incidence was 0.17% overall and 15.58% for premature infants with length of stay of more than 28 days. Our results conclusively demonstrated the importance of low birth weight as a risk for ROP development in infants with length of stay of more than 28 days, as well as association with respiratory conditions, fetal hemorrhage, intraventricular hemorrhage, and blood transfer. An interesting finding was the protective effect conferred by hypoxia, necrotizing enterocolitis, and hemolytic disease of the newborn. Infants with ROP had a higher incidence of undergoing laser photocoagulation therapy, pars plana vitrectomy, and scleral buckle surgery.The current study represents a large, retrospective analysis of newborns with ROP. The multivariate analysis emphasizes the role of birth weight in extended-stay infants, as well as respiratory conditions, fetal hemorrhage, intraventricular hemorrhage, and blood transfer.

View details for DOI 10.1016/j.ajo.2009.04.018

View details for Web of Science ID 000269755400020

View details for PubMedID 19541285

Abstract

Exsanguinating hemorrhage necessitating massive blood product transfusion is associated with high mortality rates. Recent data suggest that altering the fresh frozen plasma to packed red blood cell ratio (FFP:PRBC) results in significant mortality reductions. Our purpose was to evaluate mortality and blood product use in the context of a newly initiated massive transfusion protocol (MTP).In July 2005, our American College of Surgeons-verified Level I trauma center implemented an MTP supporting a 1:1.5 FFP:PRBC ratio, improved communications, and enhanced systems flow to optimize rapid blood product availability. During the 4 years surrounding protocol implementation, we reviewed data on trauma patients directly admitted through the emergency department and requiring 10 or more units PRBCs during the first 24 hours.For the 2 years before and subsequent to MTP initiation, there were 4,223 and 4,414 trauma activations, of which 40 and 37 patients, respectively, met study criteria. The FFP:PRBC ratios were identical, at 1:1.8 and 1:1.8 (p = 0.97). Despite no change in FFP:PRBC ratio, mortality decreased from 45% to 19% (p = 0.02). Other significant findings included decreased mean time to first product: cross-matched RBCs (115 to 71 minutes; p = 0.02), FFP (254 to 169 minutes; p = 0.04), and platelets (418 to 241 minutes; p = 0.01).MTP implementation is associated with mortality reductions that have been ascribed principally to increased plasma use and decreased FFP:PRBC ratios. Our study found a significant reduction in mortality despite unchanged FFP:PRBC ratios and equivalent overall mean numbers of transfusions. Our data underscore the importance of expeditious product availability and emphasize that massive transfusion is a complex process in which product ratio and time to transfusion represent only the beginning of understanding.

View details for DOI 10.1016/j.jamcollsurg.2009.04.016

View details for Web of Science ID 000268747300006

View details for PubMedID 19632596

Abstract

Breast cancer cell lines have been used widely to investigate breast cancer pathobiology and new therapies. Breast cancer is a molecularly heterogeneous disease, and it is important to understand how well and which cell lines best model that diversity. In particular, microarray studies have identified molecular subtypes-luminal A, luminal B, ERBB2-associated, basal-like and normal-like-with characteristic gene-expression patterns and underlying DNA copy number alterations (CNAs). Here, we studied a collection of breast cancer cell lines to catalog molecular profiles and to assess their relation to breast cancer subtypes.Whole-genome DNA microarrays were used to profile gene expression and CNAs in a collection of 52 widely-used breast cancer cell lines, and comparisons were made to existing profiles of primary breast tumors. Hierarchical clustering was used to identify gene-expression subtypes, and Gene Set Enrichment Analysis (GSEA) to discover biological features of those subtypes. Genomic and transcriptional profiles were integrated to discover within high-amplitude CNAs candidate cancer genes with coordinately altered gene copy number and expression.Transcriptional profiling of breast cancer cell lines identified one luminal and two basal-like (A and B) subtypes. Luminal lines displayed an estrogen receptor (ER) signature and resembled luminal-A/B tumors, basal-A lines were associated with ETS-pathway and BRCA1 signatures and resembled basal-like tumors, and basal-B lines displayed mesenchymal and stem/progenitor-cell characteristics. Compared to tumors, cell lines exhibited similar patterns of CNA, but an overall higher complexity of CNA (genetically simple luminal-A tumors were not represented), and only partial conservation of subtype-specific CNAs. We identified 80 high-level DNA amplifications and 13 multi-copy deletions, and the resident genes with concomitantly altered gene-expression, highlighting known and novel candidate breast cancer genes.Overall, breast cancer cell lines were genetically more complex than tumors, but retained expression patterns with relevance to the luminal-basal subtype distinction. The compendium of molecular profiles defines cell lines suitable for investigations of subtype-specific pathobiology, cancer stem cell biology, biomarkers and therapies, and provides a resource for discovery of new breast cancer genes.

View details for DOI 10.1371/journal.pone.0006146

View details for Web of Science ID 000267806300015

View details for PubMedID 19582160

Abstract

Roux-en-Y gastric bypass (RNYGB) surgery offers an effective and enduring treatment for morbid obesity. Gastric bypass may alter gastrointestinal (GI) flora possibly resulting in bacterial overgrowth and dysmotility. Our hypothesis was that daily use of probiotics would improve GI outcomes after RNYGB.Forty-four patients undergoing RNYGB were randomized to either a probiotic or control group; 2.4 billion colonies of Lactobacillus were administered daily postoperatively to the probiotic group. The outcomes of H(2) levels indicative of bacterial overgrowth, GI-related quality of life (GIQoL), serologies, and weight loss were measured preoperatively and at 3 and 6 months postoperatively. Categorical variables were analyzed by chi(2) test and continuous variables were analyzed by t test with a p < 0.05 for significance.At 6 months, a statistically significant reduction in bacterial overgrowth was achieved in the probiotic group with a preoperative to postoperative change of sum H(2) part per million (probiotics = -32.13, controls = 0.80). Surprisingly, the probiotic group attained significantly greater percent excess weight loss than that of control group at 6 weeks (controls = 25.5%, probiotic = 29.9%) and 3 months (38.55%, 47.68%). This trend also continued but was not significant at 6 months (60.78%, 67.15%). The probiotic group had significantly higher postoperative vitamin B12 levels than the control group. Both probiotic and control groups significantly improved their GIQoL.In this novel study, probiotic administration improves bacterial overgrowth, vitamin B12 availability, and weight loss after RNYGB. These data may provide further evidence that altering the GI microbiota can influence weight loss.

View details for DOI 10.1007/s11605-009-0891-x

View details for Web of Science ID 000266821800008

View details for PubMedID 19381735

View details for DOI 10.1097/FPC.0b013e32832e0ed7

View details for Web of Science ID 000267619000011

View details for PubMedID 19525887

Abstract

After an unsuccessful American College of Surgery Committee on Trauma visit, our level I trauma center initiated an improvement program that included (1) hiring new personnel (trauma director and surgeons, nurse coordinator, orthopedic trauma surgeon, and registry staff), (2) correcting deficiencies in trauma quality assurance and process improvement programs, and (3) development of an outreach program. Subsequently, our trauma center had two successful verifications. We examined the longitudinal effects of these efforts on volume, patient outcomes and finances.The Trauma Registry was used to derive data for all trauma patients evaluated in the emergency department from 2001 to 2007. Clinical data analyzed included number of admissions, interfacility transfers, injury severity scores (ISS), length of stay, and mortality for 2001 to 2007. Financial performance was assessed for fiscal years 2001 to 2007. Data were divided into patients discharged from the emergency department and those admitted to the hospital.Admissions increased 30%, representing a 7.6% annual increase (p = 0.004), mostly due to a nearly fivefold increase in interfacility transfers. Severe trauma patients (ISS >24) increased 106% and mortality rate for ISS >24 decreased by 47% to almost half the average of the National Trauma Database. There was a 78% increase in revenue and a sustained increase in hospital profitability.A major hospital commitment to Committee on Trauma verification had several salient outcomes; increased admissions, interfacility transfers, and acuity. Despite more seriously injured patients, there has been a major, sustained reduction in mortality and a trend toward decreased intensive care unit length of stay. This resulted in a substantial increase in contribution to margin (CTM), net profit, and revenues. With a high level of commitment and favorable payer mix, trauma center verification improves outcomes for both patients and the hospital.

View details for DOI 10.1097/TA.0b013e3181a51b2f

View details for Web of Science ID 000267953100035

View details for PubMedID 19590334

Abstract

To examine whether preoperative aneurysm thrombus volume correlated with abdominal aortic aneurysm (AAA) sac regression following endovascular aneurysm repair (EVAR).Clinical records and computed tomographic angiograms (CTAs) from patients undergoing EVAR from 2003 to 2008 were reviewed. Inclusion criteria for this study were available preoperative CTA images, >or=12-month follow-up with surveillance imaging, lack of re-intervention at 12 months, and treatment with commercially available devices. Patients with ruptured AAAs, those requiring an aortomonoiliac stent-graft, and clinical trial cases were excluded. Based on these criteria, satisfactory images and clinical follow-up were available in 100 patients (90 men; mean age 76.8 years, range 55-95). Preoperative CTAs were categorized as demonstrating "minimal," "moderate," or "severe" aneurysm thrombus load by 2 independent examiners blinded to clinical outcome. Percentage of the aortic cross-sectional area occluded by clot (% clot area) was calculated as [(total area) - (luminal area)]/(total area). Multivariate logistic regression analysis was performed to determine predictors of sac shrinkage at long-term follow-up.AAA thrombus was classified as minimal in 24%, moderate in 23%, and severe in 53%. Thrombus area averaged 11%+/-13%, 41%+/-14%, and 72+/-12% in each group, respectively. By multivariate analysis, minimal thrombus (OR = 1.47) and greater AAA diameter (OR = 1.3) were independent predictors of sac regression at 1, 6, and 12 months (all p<0.05). Presence of neck plaque and endoleak were also independent predictors of sac expansion (p<0.05). Patients with severe preoperative thrombus were less likely to demonstrate sac regression even in the absence of endoleak. Thrombus judgment (subjective) and percent clot area (objective) were strongly correlated (R = 0.82, p<0.05). Interobserver agreement on thrombus judgment was 86%.Thrombus burden on preoperative CTA is a strong independent predictor of sac regression following EVAR. If validated by prospective studies, relative thrombus burden should be incorporated into postoperative surveillance algorithms to define procedural success and optimize the timing and cost-effectiveness of cross-sectional imaging.

View details for Web of Science ID 000268117500019

View details for PubMedID 19642793

View details for Web of Science ID 000275277204506

View details for Web of Science ID 000275277204504

Abstract

The relationship between hospital volume and perioperative mortality in pancreaticoduodenectomy has been well established. We studied whether associations exist between hospital volume and hospital clinical resources and between both of these factors to mortality to help explain this relationship.This two-part study reviewed publicly available hospital information from the Leapfrog Group, HealthGrades, and hospital Web sites. Hospitals were evaluated for Leapfrog ICU staffing criteria and Safe Practice Score; HealthGrades five-star rating for complex gastrointestinal procedures and operations; and presence of a general surgery residency, gastroenterology fellowship, and interventional radiology. Evaluation used trend analysis and multiple logistic regression analysis. The second part determined the mortality rate for pancreaticoduodenectomy using inpatient mortality data from the National Inpatient Sample and Leapfrog. Hospitals were categorized by low volume (< or = 10/year), high volume (> or = 11/year), strong clinical support (presence of all support factors), and weak clinical support (absence of any factor). Data were correlated by number of pancreatic resections per hospital, hospital system clinical resources, and operative mortality.As hospital volume increased, statistically significant increases occurred in the frequency of hospitals meeting Leapfrog ICU staffing criteria (p < 0.0001), Leapfrog Safe Practice Score (p = 0.0004), HealthGrades 5-star rating (p < 0.00001), general surgery residency (p < 0.00001), gastroenterology fellowship (p < 0.00001), and interventional radiology services (p < 0.00001). No significant relationships were found between resection volume and any one of the clinical support factors and perioperative death. Presence of strong clinical support was associated with lower mortality (odds ratio = 0.32; p = 0.001).System clinical resources were more influential in operative mortality for pancreatic resection. This might help explain why high-volume hospitals, low-volume surgeons in high-volume institutions, and some lower-volume hospitals with excellent clinical resources have lower perioperative mortality rates for pancreatic resection.

View details for DOI 10.1016/j.jamcollsurg.2009.01.019

View details for Web of Science ID 000270996800005

View details for PubMedID 19476785

Abstract

The external carotid artery (ECA) is an important collateral pathway for cerebral blood flow. Carotid artery stenting (CAS) typically crosses the ECA, while carotid endarterectomy (CEA) includes deliberate ECA plaque removal. The purpose of the present study was to compare the long-term patency of the ECA following CAS and CEA as determined by carotid duplex ultrasound.Duplex ultrasounds and hospital records were reviewed for consecutive patients undergoing CAS between February 2002 and April 2008, and were compared with those undergoing CEA in the same time period. Preoperative and postoperative ECA peak systolic velocities were normalized to the common carotid artery (CCA) as ECA/CCA ratios. A significant (80% or greater) ECA stenosis was defined as an ECA/CCA ratio of 4.0. A change of ratio by more than 1 was defined as significant. Data were analyzed using Student's t test and ?(2) analysis.A total of 86 CAS procedures in 83 patients were performed (81 men, mean age 69.9 years). Among them, 38.4% of patients had previous CEA, 9.6% of whom had contralateral internal carotid artery occlusion. Sixty-seven CAS and 65 CEA patients with complete duplex data in the same time period were included in the analyses. There was no difference in the incidence of severe ECA stenosis on preoperative ultrasound evaluations. During a mean follow-up of 34 months (range four to 78 months), three postprocedure ECA occlusions were found in the CAS group. The likelihood of severe stenosis or occlusion following CAS was 28.3%, compared with 11% following CEA (P<0.025). However, 62% of CEA patients and 57% of CAS patients had no significant change in ECA status. Reduction in the patient's degree of ECA stenosis was observed in 9.4% of CAS versus 26.6% of CEA patients. Overall, immediate postoperative ratios of both groups were slightly improved, but there was a trend of more disease progression in the CAS group during follow-up.CAS is associated with a higher incidence of post-procedure ECA stenosis. Despite the absence of neurological symptoms, a trend toward late disease progression of ECA following CAS warrants long-term evaluation.

View details for PubMedID 22477547

Abstract

Triage of the trauma patient in the field is a complex and challenging issue, especially deciding when to use aeromedical transport. The American College of Surgeons Committee on Trauma recently defined an acceptable under-triage rate [seriously injured patient not taken to a trauma center (TC)] as 5%, whereas over-triage rates may be as high as 25% to 50%. Effective utilization of prehospital helicopter transport requires both accurate assessment of patients and effective communication. The rural county adjacent to our developed trauma system uses standardized triage criteria to identify patients for direct transport to our TCs. We hypothesized these criteria accurately identify major trauma victims (MTV) and further that communication could be simplified to expedite transport.Prehospital personnel use a MAP (mechanism, anatomy, and physiology) scoring system to triage trauma patients. Patients with > or = 2 "hits" are defined as MTV. In 2004, the triage policy was changed so that MTV would be transported directly to a TC without base hospital consultation (previously required). The Emergency Medical Services (EMS) Medical Director reviewed cases transported to the TC to determine the appropriateness of triage decisions (over- and under-triage using the American College of Surgeons Committee on Trauma definitions). Data were compared before and after this policy change.For 2004 to 2006, we evaluated 676 air transports to TC and compared them to 468 in the prior 56 months. The overall transport rate increased slightly 7% to 10%. During the study period the over-triage rate was 31% compared with 21%, before the policy change. The MAP triage tool yielded a 93.8% sensitivity and a 99.5% specificity. Therefore, it determined the need for air-medical transport out of a rural environment into an established trauma system with > 90% accuracy.Prehospital personnel can accurately use a trauma triage tool to identify MTV. Eliminating base station contact, a potential for introducing communication error, did increase over-triage but still well within accepted limits. The system change also resulted in the transport of a greater proportion of minor trauma patients who later proved to have major injuries.

View details for DOI 10.1097/TA.0b013e31818bbfc2

View details for Web of Science ID 000261706000010

View details for PubMedID 19077609

Abstract

Despite several meta-analyses and randomized controlled trials showing no benefit to patients, mechanical bowel preparation (MBP) remains the standard of practice for patients undergoing elective colorectal surgery.We performed a systematic review of the literature of trials that prospectively compared MBP with no MBP for patients undergoing elective colorectal resection. We searched MEDLINE, LILACS, and SCISEARCH, abstracts of pertinent scientific meetings and reference lists for each article found. Experts in the field were queried as to knowledge of additional reports. Outcomes abstracted were anastomotic leaks and wound infections. Meta-analysis was performed using Peto Odds ratio.Of 4,601 patients (13 trials), 2,304 received MBP (Group 1) and 2,297 did not (Group 2). Anastomotic leaks occurred in 97(4.2%) patients in Group 1 and in 81(3.5%) patients in Group 2 (Peto OR = 1.214, CI 95%:0.899-1.64, P = 0.206). Wound infections occurred in 227(9.9%) patients in Group 1 and in 201(8.8%) patients in Group 2 (Peto OR = 1.156, CI 95%:0.946-1.413, P = 0.155).This meta-analysis demonstrates that MBP provides no benefit to patients undergoing elective colorectal surgery, thus, supporting elimination of routine MBP in elective colorectal surgery.In conclusion, MBP is of no benefit to patients undergoing elective colorectal resection and need not be recommended to meet "standard of care."

View details for DOI 10.1007/s11605-008-0594-8

View details for Web of Science ID 000260282200037

View details for PubMedID 18622653

View details for Web of Science ID 000259796601370

View details for Web of Science ID 000259796600335

Abstract

Lung cancer is a leading cause of cancer death, where the amplification of oncogenes contributes to tumorigenesis. Genomic profiling of 128 lung cancer cell lines and tumors revealed frequent focal DNA amplification at cytoband 14q13.3, a locus not amplified in other tumor types. The smallest region of recurrent amplification spanned the homeobox transcription factor TITF1 (thyroid transcription factor 1; also called NKX2-1), previously linked to normal lung development and function. When amplified, TITF1 exhibited increased expression at both the RNA and protein levels. Small interfering RNA (siRNA)-mediated knockdown of TITF1 in lung cancer cell lines with amplification led to reduced cell proliferation, manifested by both decreased cell-cycle progression and increased apoptosis. Our findings indicate that TITF1 amplification and overexpression contribute to lung cancer cell proliferation rates and survival and implicate TITF1 as a lineage-specific oncogene in lung cancer.

View details for DOI 10.1038/sj.onc.1211012

View details for Web of Science ID 000256468500015

View details for PubMedID 18212743

Abstract

Pancreatobiliary cancers have among the highest mortality rates of any cancer type. Discovering the full spectrum of molecular genetic alterations may suggest new avenues for therapy. To catalogue genomic alterations, we carried out array-based genomic profiling of 31 exocrine pancreatic cancers and 6 distal bile duct cancers, expanded as xenografts to enrich the tumor cell fraction. We identified numerous focal DNA amplifications and deletions, including in 19% of pancreatobiliary cases gain at cytoband 18q11.2, a locus uncommonly amplified in other tumor types. The smallest shared amplification at 18q11.2 included GATA6, a transcriptional regulator previously linked to normal pancreas development. When amplified, GATA6 was overexpressed at both the mRNA and protein levels, and strong immunostaining was observed in 25 of 54 (46%) primary pancreatic cancers compared to 0 of 33 normal pancreas specimens surveyed. GATA6 expression in xenografts was associated with specific microarray gene-expression patterns, enriched for GATA binding sites and mitochondrial oxidative phosphorylation activity. siRNA mediated knockdown of GATA6 in pancreatic cancer cell lines with amplification led to reduced cell proliferation, cell cycle progression, and colony formation. Our findings indicate that GATA6 amplification and overexpression contribute to the oncogenic phenotypes of pancreatic cancer cells, and identify GATA6 as a candidate lineage-specific oncogene in pancreatobiliary cancer, with implications for novel treatment strategies.

View details for DOI 10.1371/journal.pgen.1000081

View details for Web of Science ID 000256869100012

View details for PubMedID 18535672

View details for Web of Science ID 000255101506282

View details for Web of Science ID 000255101506308

Abstract

PharmGKB is a knowledge base that captures the relationships between drugs, diseases/phenotypes and genes involved in pharmacokinetics (PK) and pharmacodynamics (PD). This information includes literature annotations, primary data sets, PK and PD pathways, and expert-generated summaries of PK/PD relationships between drugs, diseases/phenotypes and genes. PharmGKB's website is designed to effectively disseminate knowledge to meet the needs of our users. PharmGKB currently has literature annotations documenting the relationship of over 500 drugs, 450 diseases and 600 variant genes. In order to meet the needs of whole genome studies, PharmGKB has added new functionalities, including browsing the variant display by chromosome and cytogenetic locations, allowing the user to view variants not located within a gene. We have developed new infrastructure for handling whole genome data, including increased methods for quality control and tools for comparison across other data sources, such as dbSNP, JSNP and HapMap data. PharmGKB has also added functionality to accept, store, display and query high throughput SNP array data. These changes allow us to capture more structured information on phenotypes for better cataloging and comparison of data. PharmGKB is available at www.pharmgkb.org.

View details for DOI 10.1093/nar/gkm1009

View details for Web of Science ID 000252545400160

View details for PubMedID 18032438

Abstract

Prostate cancer is clinically heterogeneous, ranging from indolent to lethal disease. Expression profiling previously defined three subtypes of prostate cancer, one (subtype-1) linked to clinically favorable behavior, and the others (subtypes-2 and -3) linked with a more aggressive form of the disease. To explore disease heterogeneity at the genomic level, we carried out array-based comparative genomic hybridization (array CGH) on 64 prostate tumor specimens, including 55 primary tumors and 9 pelvic lymph node metastases. Unsupervised cluster analysis of DNA copy number alterations (CNA) identified recurrent aberrations, including a 6q15-deletion group associated with subtype-1 gene expression patterns and decreased tumor recurrence. Supervised analysis further disclosed distinct patterns of CNA among gene-expression subtypes, where subtype-1 tumors exhibited characteristic deletions at 5q21 and 6q15, and subtype-2 cases harbored deletions at 8p21 (NKX3-1) and 21q22 (resulting in TMPRSS2-ERG fusion). Lymph node metastases, predominantly subtype-3, displayed overall higher frequencies of CNA, and in particular gains at 8q24 (MYC) and 16p13, and loss at 10q23 (PTEN) and 16q23. Our findings reveal that prostate cancers develop via a limited number of alternative preferred genetic pathways. The resultant molecular genetic subtypes provide a new framework for investigating prostate cancer biology and explain in part the clinical heterogeneity of the disease.

View details for DOI 10.1158/0008-5472.CAN-07-0673

View details for Web of Science ID 000249679500013

View details for PubMedID 17875689

Abstract

The Stanford Microarray Database (SMD; http://smd.stanford.edu/) is a research tool and archive that allows hundreds of researchers worldwide to store, annotate, analyze and share data generated by microarray technology. SMD supports most major microarray platforms, and is MIAME-supportive and can export or import MAGE-ML. The primary mission of SMD is to be a research tool that supports researchers from the point of data generation to data publication and dissemination, but it also provides unrestricted access to analysis tools and public data from 300 publications. In addition to supporting ongoing research, SMD makes its source code fully and freely available to others under an Open Source license, enabling other groups to create a local installation of SMD. In this article, we describe several data analysis tools implemented in SMD and we discuss features of our software release.

View details for DOI 10.1093/nar/gkl1019

View details for Web of Science ID 000243494600151

View details for PubMedID 17182626

Abstract

With the completion of the Human Genome Project, a new emphasis is focusing on the sequence variation and the resulting phenotype. The number of data available from genomic studies addressing this relationship is rapidly growing. In order to analyze these data as a whole, they need to be integrated, aggregated and annotated in a timely manner. The Pharmacogenetics and Pharmacogenomics Knowledge Base PharmGKB; () assembles and disseminates these data and their associated metadata that are needed for unambiguous identification and replication. Assembling these data in a timely manner is challenging, and the scalability of these data produce major challenges for a knowledge base such as PharmGKB. However, it is only through rapid global meta-annotation of these data that we will understand the relationship between specific genotype(s) and the related phenotype. PharmGKB has confronted these challenges, and these experiences and solutions can benefit all genome communities.

View details for Web of Science ID 000243893500009

View details for PubMedID 17233563

Abstract

Breast cancer is a leading cause of cancer-death among women, where the clinicopathological features of tumors are used to prognosticate and guide therapy. DNA copy number alterations (CNAs), which occur frequently in breast cancer and define key pathogenetic events, are also potentially useful prognostic or predictive factors. Here, we report a genome-wide array-based comparative genomic hybridization (array CGH) survey of CNAs in 89 breast tumors from a patient cohort with locally advanced disease. Statistical analysis links distinct cytoband loci harboring CNAs to specific clinicopathological parameters, including tumor grade, estrogen receptor status, presence of TP53 mutation, and overall survival. Notably, distinct spectra of CNAs also underlie the different subtypes of breast cancer recently defined by expression-profiling, implying these subtypes develop along distinct genetic pathways. In addition, higher numbers of gains/losses are associated with the "basal-like" tumor subtype, while high-level DNA amplification is more frequent in "luminal-B" subtype tumors, suggesting also that distinct mechanisms of genomic instability might underlie their pathogenesis. The identified CNAs may provide a basis for improved patient prognostication, as well as a starting point to define important genes to further our understanding of the pathobiology of breast cancer. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat

View details for DOI 10.1002/gcc.20366

View details for Web of Science ID 000240601400005

View details for PubMedID 16897746

Abstract

The development of the Functional Genomics Investigation Ontology (FuGO) is a collaborative, international effort that will provide a resource for annotating functional genomics investigations, including the study design, protocols and instrumentation used, the data generated and the types of analysis performed on the data. FuGO will contain both terms that are universal to all functional genomics investigations and those that are domain specific. In this way, the ontology will serve as the "semantic glue" to provide a common understanding of data from across these disparate data sources. In addition, FuGO will reference out to existing mature ontologies to avoid the need to duplicate these resources, and will do so in such a way as to enable their ease of use in annotation. This project is in the early stages of development; the paper will describe efforts to initiate the project, the scope and organization of the project, the work accomplished to date, and the challenges encountered, as well as future plans.

View details for Web of Science ID 000240210900016

View details for PubMedID 16901226

View details for PubMedID 16610446

Abstract

DNA amplifications and deletions frequently contribute to the development and progression of lung cancer. To identify such novel alterations in small cell lung cancer (SCLC), we performed comparative genomic hybridization on a set of 24 SCLC cell lines, using cDNA microarrays representing approximately 22,000 human genes (providing an average mapping resolution of <70 kb). We identified localized DNA amplifications corresponding to oncogenes known to be amplified in SCLC, including MYC (8q24), MYCN (2p24) and MYCL1 (1p34). Additional highly localized DNA amplifications suggested candidate oncogenes not previously identified as amplified in SCLC, including the antiapoptotic genes TNFRSF4 (1p36), DAD1 (14q11), BCL2L1 (20q11) and BCL2L2 (14q11). Likewise, newly discovered PCR-validated homozygous deletions suggested candidate tumor-suppressor genes, including the proapoptotic genes MAPK10 (4q21) and TNFRSF6 (10q23). To characterize the effect of DNA amplification on gene expression patterns, we performed expression profiling using the same microarray platform. Among our findings, we identified sets of genes whose expression correlated with MYC, MYCN or MYCL1 amplification, with surprisingly little overlap among gene sets. While both MYC and MYCN amplification were associated with increased and decreased expression of known MYC upregulated and downregulated targets, respectively, MYCL1 amplification was associated only with the latter. Our findings support a role of altered apoptotic balance in the pathogenesis of SCLC, and suggest that MYC family genes might affect oncogenesis through distinct sets of targets, in particular implicating the importance of transcriptional repression.

View details for DOI 10.1038/sj.onc.1208997

View details for Web of Science ID 000234406400014

View details for PubMedID 16116477

Abstract

The molecular basis of renal aging is not completely understood.We used global gene expression monitoring by cDNA microarrays to identify age associated genes in human kidney samples. Our samples included young (8 weeks-8 years, N= 4), adult (31-46 years, N= 7), and old kidneys (71-88 years, N= 9).Old kidneys had more glomerulosclerosis, tubular atrophy, interstitial fibrosis, and fibrous intimal thickening in small arteries. We identified approximately 500 genes that were differentially expressed among the three age groups. Old kidneys appeared to have increased extracellular matrix turnover and a nonspecific inflammatory response, combined with a reduction in processes dependent on energy metabolism and mitochondrial function. Quantitative supervised bioinformatics analyses of adult and old kidney expression data correlated the expression of 255 gene profiles with renal pathology scores. Microarray class prediction analysis (PAM) identified 50 unique genes that segregated old kidneys into two distinct clusters: those more similar within age class (OO, N= 5) versus old kidneys more similar to adult kidneys (OA, N= 4). The expression of six functionally significant genes was further validated by quantitative reverse transcription-polymerase chain reaction (RT-PCR) (FN1, MMP7, TNC, SERPIN3A, BPHL, CSPG2) in the experiment group and, subsequently, confirmed independently in 17 additional old and adult age-stratified test kidney samples. The p53 inducible gene, CSPG2, performed best in separating OO kidneys from adults and OA samples in this analysis.The method described in this study using independent validation samples can be envisioned to test utility of the identified genes in assessing age-related changes that contribute to decline in renal function.

View details for Web of Science ID 000233204300022

View details for PubMedID 16316342

Abstract

Microarray-based formats offer a high-resolution alternative to conventional, chromosome-based comparative genomic hybridization (CGH) methods for assessing DNA copy number alteration (CNA) genome-wide in human cancer. For murine tumors, array CGH should provide even greater advantage, since murine chromosomes are more difficult to individually discern. We report here the adaptation and evaluation of a cDNA microarray-based CGH method for the routine characterization of CNAs in murine tumors, using mouse cDNA microarrays representing approximately 14,000 different genes, thereby providing an average mapping resolution of 109 kb. As a first application, we have characterized CNAs in a set of 10 primary and recurrent lymphomas derived from a Myc-induced murine lymphoma model. In primary lymphomas and more commonly in Myc-independent relapses, we identified a recurrent genomic DNA loss at chromosome 3G3-3H4, and recurrent amplifications at chromosome 3F2.1-3G3 and chromosome 15E1/E2-15F3, the boundaries of which we defined with high resolution. Further, by profiling gene expression using the same microarray platform, we identified within CNAs the relevant subset of candidate cancer genes displaying comparably altered expression, including Mcl1 (myeloid cell leukemia sequence 1), a highly expressed antiapoptotic gene residing within the chr 3 amplicon peak. CGH on mouse cDNA microarrays therefore represents a reliable method for the high-resolution characterization of CNAs in murine tumors, and a powerful approach for elucidating the molecular events in tumor development and progression in murine models.

View details for DOI 10.1038/sj.onc.1208751

View details for Web of Science ID 000231718100004

View details for PubMedID 16007205

Abstract

Pancreatic cancer, the fourth leading cause of cancer death in the United States, is frequently associated with the amplification and deletion of specific oncogenes and tumor-suppressor genes (TSGs), respectively. To identify such novel alterations and to discover the underlying genes, we performed comparative genomic hybridization on a set of 22 human pancreatic cancer cell lines, using cDNA microarrays measuring approximately 26,000 human genes (thereby providing an average mapping resolution of <60 kb). To define the subset of amplified and deleted genes with correspondingly altered expression, we also profiled mRNA levels in parallel using the same cDNA microarray platform. In total, we identified 14 high-level amplifications (38-4934 kb in size) and 15 homozygous deletions (46-725 kb). We discovered novel localized amplicons, suggesting previously unrecognized candidate oncogenes at 6p21, 7q21 (SMURF1, TRRAP), 11q22 (BIRC2, BIRC3), 12p12, 14q24 (TGFB3), 17q12, and 19q13. Likewise, we identified novel polymerase chain reaction-validated homozygous deletions indicating new candidate TSGs at 6q25, 8p23, 8p22 (TUSC3), 9q33 (TNC, TNFSF15), 10q22, 10q24 (CHUK), 11p15 (DKK3), 16q23, 18q23, 21q22 (PRDM15, ANKRD3), and Xp11. Our findings suggest candidate genes and pathways, which may contribute to the development or progression of pancreatic cancer.

View details for DOI 10.1593/neo.04586

View details for Web of Science ID 000230209600002

View details for PubMedID 16036106

Abstract

Many soft tissue tumors recapitulate features of normal connective tissue. We hypothesize that different types of fibroblastic tumors are representative of different populations of fibroblastic cells or different activation states of these cells. We examined two tumors with fibroblastic features, solitary fibrous tumor (SFT) and desmoid-type fibromatosis (DTF), by DNA microarray analysis and found that they have very different expression profiles, including significant differences in their patterns of expression of extracellular matrix genes and growth factors. Using immunohistochemistry and in situ hybridization on a tissue microarray, we found that genes specific for these two tumors have mutually specific expression in the stroma of nonneoplastic tissues. We defined a set of 786 gene spots whose pattern of expression distinguishes SFT from DTF. In an analysis of DNA microarray gene expression data from 295 previously published breast carcinomas, we found that expression of this gene set defined two groups of breast carcinomas with significant differences in overall survival. One of the groups had a favorable outcome and was defined by the expression of DTF genes. The other group of tumors had a poor prognosis and showed variable expression of genes enriched for SFT type. Our findings suggest that the host stromal response varies significantly among carcinomas and that gene expression patterns characteristic of soft tissue tumors can be used to discover new markers for normal connective tissue cells.

View details for DOI 10.1371/journal.pbio.0030187

View details for Web of Science ID 000229992900019

View details for PubMedID 15869330

Abstract

Recent studies have demonstrated that both mouse and human alpha beta TCR(+)CD3(+)NK1.1(-)CD4(-)CD8- double-negative regulatory T (DN Treg) cells can suppress Ag-specific immune responses mediated by CD8+ and CD4+ T cells. To identify molecules involved in DN Treg cell function, we generated a panel of murine DN Treg clones, which specifically kill activated syngeneic CD8+ T cells. Through serial cultivation of DN Treg clones, mutant clones arose that lost regulatory capacity in vitro and in vivo. Although all allogeneic cardiac grafts in animals preinfused with tolerant CD4/CD8 negative 12 DN Treg clones survived over 100 days, allograft survival is unchanged following infusion of mutant clones (19.5 +/- 11.1 days) compared with untreated controls (22.8 +/- 10.5 days; p < 0.001). Global gene expression differences between functional DN Treg cells and nonfunctional mutants were compared. We found 1099 differentially expressed genes (q < 0.025%), suggesting increased cell proliferation and survival, immune regulation, and chemotaxis, together with decreased expression of genes for Ag presentation, apoptosis, and protein phosphatases involved in signal transduction. Expression of 33 overexpressed and 24 underexpressed genes were confirmed using quantitative real-time PCR. Protein expression of several genes, including Fc epsilon RI gamma subunit and CXCR5, which are >50-fold higher, was also confirmed using FACS. These findings shed light on the mechanisms by which DN Treg cells down-regulate immune responses and prolong cardiac allograft survival.

View details for Web of Science ID 000228234600014

View details for PubMedID 15814674

Abstract

The Stanford Microarray Database (SMD) (http://smd.stanford.edu) is a research tool for hundreds of Stanford researchers and their collaborators. In addition, SMD functions as a resource for the entire biological research community by providing unrestricted access to microarray data published by SMD users and by disseminating its source code. In addition to storing GenePix (Axon Instruments) and ScanAlyze output from spotted microarrays, SMD has recently added the ability to store, retrieve, display and analyze the complete raw data produced by several additional microarray platforms and image analysis software packages, so that we can also now accept data from Affymetrix GeneChips (MAS5/GCOS or dChip), Agilent Catalog or Custom arrays (using Agilent's Feature Extraction software) or data created by SpotReader (Niles Scientific). We have implemented software that allows us to accept MAGE-ML documents from array manufacturers and to submit MIAME-compliant data in MAGE-ML format directly to ArrayExpress and GEO, greatly increasing the ease with which data from SMD can be published adhering to accepted standards and also increasing the accessibility of published microarray data to the general public. We have introduced a new tool to facilitate data sharing among our users, so that datasets can be shared during, before or after the completion of data analysis. The latest version of the source code for the complete database package was released in November 2004 (http://smd.stanford.edu/download/), allowing researchers around the world to deploy their own installations of SMD.

View details for Web of Science ID 000226524300119

View details for PubMedID 15608265

Abstract

Microarray-based comparative genome hybridization experiments generate data that can be mapped onto the genome. These data are interpreted more easily when represented graphically in a genomic context.We have developed Caryoscope, which is an open source Java application for visualizing microarray data from array comparative genome hybridization experiments in a genomic context. Caryoscope can read General Feature Format files (GFF files), as well as comma- and tab-delimited files, that define the genomic positions of the microarray reporters for which data are obtained. The microarray data can be browsed using an interactive, zoomable interface, which helps users identify regions of chromosomal deletion or amplification. The graphical representation of the data can be exported in a number of graphic formats, including publication-quality formats such as PostScript.Caryoscope is a useful tool that can aid in the visualization, exploration and interpretation of microarray data in a genomic context.

View details for DOI 10.1186/1471-2105-5-151

View details for Web of Science ID 000225769900002

View details for PubMedID 15488149

Abstract

Most GISTs require oncogenic activation of the KIT or PDGFRA receptor tyrosine kinase proteins, and the genomic mechanisms of oncogene activation are heterogeneous. Notably, the kinase mutation type correlates with both tumor biology and imatinib response. For example, GISTs with KIT exon 11 mutations are typically gastric and have excellent imatinib response, whereas those with KIT exon 9 mutations generally arise in the small bowel and are less responsive to imatinib. To identify genes that might contribute to these biological differences, we carried out gene expression profiling of 26 GISTs with known KIT and PDGFRA mutational status. Expression differences were then evaluated further by RNA in situ hybridization, immunohistochemistry, and immunoblotting. Unsupervised hierarchical clustering grouped tumors with similar mutations together, but the distinction between the different groups was not absolute. Differentially expressed genes included ezrin, p70S6K, and PKCs, which are known to have key roles in KIT or PDGFRA signaling, and which might therefore contribute to the distinctive clinicopathological features in GISTs with different mutation types. These gene products could serve as highly selective therapeutic targets in GISTs containing the KIT or PDGFRA mutational types with which they are associated.

View details for DOI 10.1038/sj.onc.1208056

View details for Web of Science ID 000224331600004

View details for PubMedID 15326474

View details for Web of Science ID 000224109400023

Abstract

Expression profiling studies classified breast carcinomas into estrogen receptor (ER)+/luminal, normal breast-like, HER2 overexpressing, and basal-like groups, with the latter two associated with poor outcomes. Currently, there exist clinical assays that identify ER+/luminal and HER2-overexpressing tumors, and we sought to develop a clinical assay for breast basal-like tumors.To identify an immunohistochemical profile for breast basal-like tumors, we collected a series of known basal-like tumors and tested them for protein patterns that are characteristic of this subtype. Next, we examined the significance of these protein patterns using tissue microarrays and evaluated the prognostic significance of these findings.Using a panel of 21 basal-like tumors, which was determined using gene expression profiles, we saw that this subtype was typically immunohistochemically negative for estrogen receptor and HER2 but positive for basal cytokeratins, HER1, and/or c-KIT. Using breast carcinoma tissue microarrays representing 930 patients with 17.4-year mean follow-up, basal cytokeratin expression was associated with low disease-specific survival. HER1 expression was observed in 54% of cases positive for basal cytokeratins (versus 11% of negative cases) and was associated with poor survival independent of nodal status and size. c-KIT expression was more common in basal-like tumors than in other breast cancers but did not influence prognosis.A panel of four antibodies (ER, HER1, HER2, and cytokeratin 5/6) can accurately identify basal-like tumors using standard available clinical tools and shows high specificity. These studies show that many basal-like tumors express HER1, which suggests candidate drugs for evaluation in these patients.

View details for Web of Science ID 000223454600011

View details for PubMedID 15328174

Abstract

Using gene microarray expression profiling, we previously found that apolipoprotein D (Apo D) was highly expressed in dermatofibrosarcoma protuberans (DFSP). In this study, we confirm that Apo D is highly and relatively specifically expressed in DFSP using immunohistochemistry. A tissue microarray containing 421 soft tissue tumors was constructed and stained with antibodies against Apo D and CD34. Cytoplasmic immunostaining for Apo D was found in 9 of 10 typical DFSPs. In addition, 3 of 3 Bednar tumors and 2 of 3 giant cell fibroblastomas stained in conventional sections. In contrast, Apo D was immunoreactive in only a very small subset of a diverse collection of other soft tissue tumors, including Malignant Fibrous Histiocytoma (MFH), glomus tumor, neurofibroma, and malignant peripheral nerve sheath tumors. Immunostains for Apo D were negative in conventional sections of 16 fibrous histiocytomas, and an additional 12 variants of fibrous histiocytoma. Digital images of all immunohistochemical and hematoxylin and eosin tissue microarray stains are available at the accompanying website (http://microarray-pubs.stanford.edu/tma_portal/apod/). We conclude that Apo D is strongly expressed in DFSPs and neural lesions and may be useful in differentiating DFSP from fibrous histiocytoma.

View details for Web of Science ID 000222891400012

View details for PubMedID 15252314

View details for DOI 10.1371/journal.pbio.0020207

View details for Web of Science ID 000222977900012

Abstract

Given that gene duplication is a major driving force of evolutionary change and the key mechanism underlying the emergence of new genes and biological processes, this study sought to use a novel genome-wide approach to identify genes that have undergone lineage-specific duplications or contractions among several hominoid lineages. Interspecies cDNA array-based comparative genomic hybridization was used to individually compare copy number variation for 39,711 cDNAs, representing 29,619 human genes, across five hominoid species, including human. We identified 1,005 genes, either as isolated genes or in clusters positionally biased toward rearrangement-prone genomic regions, that produced relative hybridization signals unique to one or more of the hominoid lineages. Measured as a function of the evolutionary age of each lineage, genes showing copy number expansions were most pronounced in human (134) and include a number of genes thought to be involved in the structure and function of the brain. This work represents, to our knowledge, the first genome-wide gene-based survey of gene duplication across hominoid species. The genes identified here likely represent a significant majority of the major gene copy number changes that have occurred over the past 15 million years of human and great ape evolution and are likely to underlie some of the key phenotypic characteristics that distinguish these species.

View details for PubMedID 15252450

Abstract

Distinguishing between Spitz nevus and melanoma presents a challenging task for clinicians and pathologists. Most of these lesions are submitted entirely in formalin for histologic analysis by conventional hematoxylin and eosin-stained sections, and fresh-frozen material for ancillary studies is rarely collected. Molecular techniques, such as comparative genomic hybridization (CGH), can detect chromosomal alterations in tumor DNA that differ between these 2 lesions. This study investigated the ability of high-resolution array-based CGH to serve as a diagnostic test in distinguishing Spitz nevus and melanoma using DNA isolated from formalin-fixed and paraffin-embedded samples. Two of 3 Spitz nevi exhibited no significant chromosomal alterations, while the third showed gain of the short arm of chromosome 11p. The latter finding has previously been described as characteristic of a subset of Spitz nevi. The 2 melanomas showed multiple copy number alterations characteristic of melanoma such as 1q amplification and chromosome 9 deletion. This study has shown the utility of array-based CGH as a potential molecular test in distinguishing Spitz nevus from melanoma. The assay is capable of using archival paraffin-embedded, formalin-fixed material; is technically easier to perform as compared with conventional CGH; is more sensitive than conventional CGH in being able to detect focal alterations; and can detect copy number alterations even with relatively small amounts of lesional tissue as is typical of many skin tumors.

View details for Web of Science ID 000189276600004

View details for PubMedID 15163005

Abstract

Dermatofibrosarcoma protuberans (DFSP) is an aggressive spindle cell neoplasm. It is associated with the chromosomal translocation, t(17:22), which fuses the COL1A1 and PDGFbeta genes. We determined the characteristic gene expression profile of DFSP and characterized DNA copy number changes in DFSP by array-based comparative genomic hybridization (array CGH). Fresh frozen and formalin-fixed, paraffin-embedded samples of DFSP were analyzed by array CGH (four cases) and DNA microarray analysis of global gene expression (nine cases). The nine DFSPs were readily distinguished from 27 other diverse soft tissue tumors based on their gene expression patterns. Genes characteristically expressed in the DFSPs included PDGF beta and its receptor, PDGFRB, APOD, MEOX1, PLA2R, and PRKCA. Array CGH of DNA extracted either from frozen tumor samples or from paraffin blocks yielded equivalent results. Large areas of chromosomes 17q and 22q, bounded by COL1A1 and PDGF beta, respectively, were amplified in DFSP. Expression of genes in the amplified regions was significantly elevated. Our data shows that: 1) DFSP has a distinctive gene expression profile; 2) array CGH can be applied successfully to frozen or formalin-fixed, paraffin-embedded tumor samples; 3) a characteristic amplification of sequences from chromosomes 17q and 22q, demarcated by the COL1A1 and PDGF beta genes, respectively, was associated with elevated expression of the amplified genes.

View details for Web of Science ID 000186769800024

View details for PubMedID 14633610

Abstract

We used DNA microarrays to characterize the global gene expression patterns in surface epithelial cancers of the ovary. We identified groups of genes that distinguished the clear cell subtype from other ovarian carcinomas, grade I and II from grade III serous papillary carcinomas, and ovarian from breast carcinomas. Six clear cell carcinomas were distinguished from 36 other ovarian carcinomas (predominantly serous papillary) based on their gene expression patterns. The differences may yield insights into the worse prognosis and therapeutic resistance associated with clear cell carcinomas. A comparison of the gene expression patterns in the ovarian cancers to published data of gene expression in breast cancers revealed a large number of differentially expressed genes. We identified a group of 62 genes that correctly classified all 125 breast and ovarian cancer specimens. Among the best discriminators more highly expressed in the ovarian carcinomas were PAX8 (paired box gene 8), mesothelin, and ephrin-B1 (EFNB1). Although estrogen receptor was expressed in both the ovarian and breast cancers, genes that are coregulated with the estrogen receptor in breast cancers, including GATA-3, LIV-1, and X-box binding protein 1, did not show a similar pattern of coexpression in the ovarian cancers.

View details for Web of Science ID 000186738300005

View details for PubMedID 12960427

Abstract

The Stanford Microarray Database (SMD; http://genome-www.stanford.edu/microarray/) serves as a microarray research database for Stanford investigators and their collaborators. In addition, SMD functions as a resource for the entire scientific community, by making freely available all of its source code and providing full public access to data published by SMD users, along with many tools to explore and analyze those data. SMD currently provides public access to data from 3500 microarrays, including data from 85 publications, and this total is increasing rapidly. In this article, we describe some of SMD's newer tools for accessing public data, assessing data quality and for data analysis.

View details for DOI 10.1093/nar/gkg078

View details for Web of Science ID 000181079700020

View details for PubMedID 12519956

Abstract

The explosion in the number of functional genomic datasets generated with tools such as DNA microarrays has created a critical need for resources that facilitate the interpretation of large-scale biological data. SOURCE is a web-based database that brings together information from a broad range of resources, and provides it in manner particularly useful for genome-scale analyses. SOURCE's GeneReports include aliases, chromosomal location, functional descriptions, GeneOntology annotations, gene expression data, and links to external databases. We curate published microarray gene expression datasets and allow users to rapidly identify sets of co-regulated genes across a variety of tissues and a large number of conditions using a simple and intuitive interface. SOURCE provides content both in gene and cDNA clone-centric pages, and thus simplifies analysis of datasets generated using cDNA microarrays. SOURCE is continuously updated and contains the most recent and accurate information available for human, mouse, and rat genes. By allowing dynamic linking to individual gene or clone reports, SOURCE facilitates browsing of large genomic datasets. Finally, SOURCEs batch interface allows rapid extraction of data for thousands of genes or clones at once and thus facilitates statistical analyses such as assessing the enrichment of functional attributes within clusters of genes. SOURCE is available at http://source.stanford.edu.

View details for DOI 10.1093/nar/gkg014

View details for Web of Science ID 000181079700050

View details for PubMedID 12519986

Abstract

TP53 encodes p53, which is a nuclear phosphoprotein with cancer-inhibiting properties. In response to DNA damage, p53 is activated and mediates a set of antiproliferative responses including cell-cycle arrest and apoptosis. Mutations in the TP53 gene are associated with more than 50% of human cancers, and 90% of these affect p53-DNA interactions, resulting in a partial or complete loss of transactivation functions. These mutations affect the structural integrity and/or p53-DNA interactions, leading to the partial or complete loss of the protein's function. We report here the results of a systematic automated analysis of the effects of p53 mutations on the structure of the core domain of the protein. We found that 304 of the 882 (34.4%) distinct mutations reported in the core domain can be explained in structural terms by their predicted effects on protein folding or on protein-DNA contacts. The proportion of "explained" mutations increased to 55.6% when substitutions of evolutionary conserved amino acids were included. The automated method of structural analysis developed here may be applied to other frequently mutated gene mutations such as dystrophin, BRCA1, and G6PD.

View details for Web of Science ID 000173628700008

View details for PubMedID 11793474

Abstract

The Stanford Microarray Database (SMD) stores raw and normalized data from microarray experiments, and provides web interfaces for researchers to retrieve, analyze and visualize their data. The two immediate goals for SMD are to serve as a storage site for microarray data from ongoing research at Stanford University, and to facilitate the public dissemination of that data once published, or released by the researcher. Of paramount importance is the connection of microarray data with the biological data that pertains to the DNA deposited on the microarray (genes, clones etc.). SMD makes use of many public resources to connect expression information to the relevant biology, including SGD [Ball,C.A., Dolinski,K., Dwight,S.S., Harris,M.A., Issel-Tarver,L., Kasarskis,A., Scafe,C.R., Sherlock,G., Binkley,G., Jin,H. et al. (2000) Nucleic Acids Res., 28, 77-80], YPD and WormPD [Costanzo,M.C., Hogan,J.D., Cusick,M.E., Davis,B.P., Fancher,A.M., Hodges,P.E., Kondu,P., Lengieza,C., Lew-Smith,J.E., Lingner,C. et al. (2000) Nucleic Acids Res., 28, 73-76], Unigene [Wheeler,D.L., Chappey,C., Lash,A.E., Leipe,D.D., Madden,T.L., Schuler,G.D., Tatusova,T.A. and Rapp,B.A. (2000) Nucleic Acids Res., 28, 10-14], dbEST [Boguski,M.S., Lowe,T.M. and Tolstoshev,C.M. (1993) Nature Genet., 4, 332-333] and SWISS-PROT [Bairoch,A. and Apweiler,R. (2000) Nucleic Acids Res., 28, 45-48] and can be accessed at http://genome-www.stanford.edu/microarray.

View details for Web of Science ID 000166360300039

View details for PubMedID 11125075

Abstract

The tumor suppressor p53 gene is the most frequently mutated gene in human cancer. To date, more than 10,000 mutations have been described in the literature, and these data are available in various electronic formats on the World Wide Web. Here we describe the structure and format of the different p53 datasets maintained and curated at the International Agency for Research on Cancer (IARC) in Lyon, France. These include p53 somatic mutations (more than 10,000 entries), p53 germline mutations (144 entries), and p53 polymorphisms (13 entries), with the somatic mutations organized into a relational database using AccessTM. The main features of these datasets are (1) controlled entry with standardized format and restricted vocabulary, (2) inclusion of annotations on individual characteristics and exposures, and (3) a classification of pathologies based on the International Classification of Diseases for Oncology (ICD-O). In addition, several interfaces have been developed to analyze the data in order to produce mutation spectra, codon analyses, or visualization of the mutation with the tertiary structure of the protein. All datasets and tools for analysis are available at http://www.iarc.fr/p53/homepage.

View details for Web of Science ID 000081207100001

View details for PubMedID 10447253

Abstract

Mutations in the p53 gene are common in lung cancer. Using data from the the International Agency for Research on Cancer p53 mutation database (R1), we have analyzed the distribution and nature of p53 mutations in 876 lung tumors described in the literature. These analyses confirm that G to T transitions are the predominant type of p53 mutation in lung cancer from smokers. The most frequently mutated codons include 157, 158, 179, 248, 249, and 273, and several of them (157, 248, and 273) have been shown to correspond to sites of in vitro DNA adduct formation by metabolites of polycyclic aromatic hydrocarbons (PAHs) such as benzo(a)pyrene. Furthermore, most of the base changes at codons 248, 249, and 273 in lung cancer differ from those commonly observed at these codons in other cancers reported in the database. Thus, lung cancer from smokers shows a distinct, unique p53 mutation spectrum that is not observed in lung cancer from nonsmokers. These results further strengthen the association between active smoking, exposure to PAHs, and lung cancer. They also indicate that a different pattern of mutations occurs in nonsmokers, and this observation may help to identify other agents causally involved in lung cancer in nonsmokers.

View details for Web of Science ID 000075380700018

View details for PubMedID 9637795

Abstract

Since 1989, about 570 different p53 mutations have been identified in more than 8000 human cancers. A database of these mutations was initiated by M. Hollstein and C. C. Harris in 1990. This database originally consisted of a list of somatic point mutations in the p 53 gene of human tumors and cell lines, compiled from the published literature and made available in a standard electronic form. The database is maintained at the International Agency for Research on Cancer (IARC) and updated versions are released twice a year (January and July). The current version (July 1997) contains records on 6800 published mutations and will surpass the 8000 mark in the January 1998 release. The database now contains information on somatic and germline mutations in a new format to facilitate data retrieval. In addition, new tools are constructed to improve data analysis, such as a Mutation Viewer Java applet developed at the European Bioinformatics Institute (EBI) to visualise the location and impact of mutations on p53 protein structure. The database is available in different electronic formats at IARC (http://www.iarc. fr/p53/homepage.htm ) or from the EBI server (http://www.ebi.ac.uk ). The IARC p53 website also provides reports on database analysis and links with other p53 sites as well as with related databases. In this report, we describe the criteria for inclusion of data, the revised format and the new visualisation tools. We also briefly discuss the relevance of p 53 mutations to clinical and biological questions.

View details for Web of Science ID 000071778900049

View details for PubMedID 9399837