Wayne Frederick

Negative appendectomy: a 10-year review of a nationally representative sample

BACKGROUND Appendectomy remains one of the most common emergency surgical procedures encountered throughout the United States. With improvements in diagnostic techniques, the efficiency of diagnosis has increased over the years. However, the entity of negative appendectomies still poses a dilemma because these are associated with unnecessary risks and costs to both patients and institutions. This study was conducted to show current statistics and trends in negative appendectomy rates in the United States. METHODS A retrospective analysis was conducted using data from the National Inpatient Sample from 1998 to 2007. Adult patients (>18 y) having undergone appendectomies were identified by the appropriate International Classification of Diseases 9th revision codes. Patients with incidental appendectomy and those with appendiceal pathologies, also identified by relevant International Classification of Diseases 9th revision codes, were excluded. The remaining patients represent those who underwent an appendectomy without appendiceal disease. The patients then were stratified according to sex, women were classified further into younger (18-45 y) and older (>45 y) based on child-bearing age. The primary diagnoses subsequently were categorized by sex to identify the most common conditions mistaken for appendiceal disease in the 2 groups. RESULTS Between 1998 and 2007, there were 475,651 cases of appendectomy that were isolated. Of these, 56,252 were negative appendectomies (11.83%). There was a consistent decrease in the negative appendectomy rates from 14.7% in 1998 to 8.47% in 2007. Women accounted for 71.6% of cases of negative appendectomy, and men accounted for 28.4%. The mortality rate was 1.07%, men were associated with a higher rate of mortality (1.93% vs .74%; P < .001). Ovarian cyst was the most common diagnosis mistaken for appendicitis in younger women, whereas malignant disease of the ovary was the most common condition mistaken for appendiceal disease in women ages 45 and older. The most common misdiagnosis in men was diverticulitis of the colon. CONCLUSIONS There has been a consistent decline in the rates of negative appendectomy. This trend may be attributed to better diagnostics. Gynecologic conditions involving the ovary are the most common to be misdiagnosed as appendiceal disease in women.

Inhibition of constitutive NF-kappa B activity by I kappa B alpha M suppresses tumorigenesis.

We have demonstrated that nuclear factor-κB (NF-κB) is constitutively activated in human pancreatic adenocarcinoma and human pancreatic cancer cell lines but not in normal pancreatic tissues or in immortalized, nontumorigenic pancreatic epithelial cells, suggesting that NF-κB plays a critical role in the development of pancreatic adenocarcinoma. To elucidate the role of constitutive NF-κB activity in human pancreatic cancer cells, we generated pancreatic tumor cell lines that express a phosphorylation defective IκBα (S32, 36A) (IκBαM) that blocks NF-κB activity. In this study, we showed that inhibiting constitutive NF-κB activity by expressing IκBαM suppressed the tumorigenicity of a nonmetastatic human pancreatic cancer cell line, PANC-1, in an orthotopic nude mouse model. Immunohistochemical analysis showed that PANC-1-derived tumors expressed vascular endothelial growth factor (VEGF) and induced angiogenesis. Inhibiting NF-κB signaling by expressing IκBαM significantly reduced expression of Bcl-xL and Bcl-2. The cytokine-induced expression of VEGF and Interleukin-8 in PANC-1 cells is also decreased. Taken together, these results suggest that the inhibition of NF-κB signaling can suppress tumorigenesis of pancreatic cancer cells and that the NF-κB signaling pathway is a potential target for anticancer agents.

Molecular Breast Cancer Subtypes in Premenopausal African-American Women, Tumor Biologic Factors and Clinical Outcome

IntroductionBreast cancer is currently viewed as a heterogeneous disease made up of various subtypes, with distinct differences in prognosis. Our goal was to study the distribution and to characterize the clinical and biological factors that influence the behavior and clinical management of the different molecular breast cancer subtypes in premenopausal African-American women.MethodsA retrospective analysis of Howard University Hospital tumor registry, for all premenopausal African-American women aged less than 50 years, diagnosed with breast cancer from 1998–2005, was performed.ResultsThe luminal A subtype was the most prevalent (50.0%), vs basal-cell-like (23.2%), luminal B (14.1%), and HER-2/neu (12.7%). However when stratified by age groups, results showed that in the age group <35 years the basal-cell-like subtype was the most prevalent (55.6%), vs 25.9%, 14.8%, and 5.6% for luminal A, luminal B, and HER-2/neu subtypes, respectively (P < .000). P53 mutation was more prevalent in the basal-cell-like subtype compared to luminal A (48.0% vs 18.6%, P < .01).The expression of the Bcl-2 gene differed by subtype, with the luminal A and luminal B subtypes more likely to overexpress the Bcl-2 gene (89.1% luminal A, 80.0% luminal B vs 47.6% basal-cell-like and 40.0% HER-2/neu, P < .000). Though not statistically significant, HER-2/neu and basal-cell-like subtypes had the shortest survival time (P < .31).ConclusionThe high prevalence of the basal-cell-like subtype in young premenopausal African-American women aged <35 years may contribute to the poorer prognosis observed in this cohort of African-American women.

Early-stage gallbladder cancer in the Surveillance, Epidemiology, and End Results database: effect of extended surgical resection.

HYPOTHESIS Extended surgical resection (ESR) may improve survival in patients with early-stage primary gallbladder cancer. DESIGN Retrospective analysis of findings in the Surveillance, Epidemiology, and End Results (SEER) database. SETTING Academic research. PATIENTS Individuals with potentially surgically curable gallbladder cancer (Tis, T1, or T2) who underwent a surgical procedure. MAIN OUTCOME MEASURES Overall survival, number of lymph nodes (LNs) excised, and results of simple cholecystectomy vs ESR. RESULTS We identified 3209 patients with early-stage gallbladder cancer (11.7% Tis, 30.1% T1, and 58.2% T2). On multivariate analysis, decreased survival was noted among patients older than 60 years (hazard ratio, 1.57; 95% confidence interval, 1.30-1.90), among patients with more advanced cancer (1.99; 1.46-2.70 for T1; 3.29; 2.45-4.43 for T2), and among patients with disease-positive LNs (1.65; 1.39-1.95 for regional; 2.58; 1.54-4.34 for distant) (P < .001 for all), while increased survival was observed among female patients (0.82; 0.70-0.96; P = .02) and among patients undergoing ESR (0.59; 0.45-0.78; P < .001). The survival advantage of ESR was seen only in patients with T2 lesions (0.49; 0.35-0.68; P < .001). Lymph node excision data were available for a subset of 2507 patients, of whom 68.2% had no LN excised, 28.2% had 1 to 4 LNs excised, and 3.6% had 5 or more LNs excised. On multivariate analysis, patients with 1 to 4 LNs excised had a survival benefit over those with no LN excised (HR, 0.55; 95% CI, 0.46-0.66; P < .001), and patients with 5 or more LNs excised had a survival benefit over patients with 1 to 4 LNs removed (0.63; 0.40-0.96; P = .03). Lymph node excision improved survival in patients with T2 lesions (0.42; 0.33-0.53; P < .001 for patients with 1-4 LNs excised). CONCLUSION Extended surgical resection, LN excision, or both may improve survival in certain patients with incidentally discovered gallbladder cancer.

Treatment and Survival Outcome for Molecular Breast Cancer Subtypes in Black Women

Objective:To analyze whether the local-regional surgical treatments (breast-conserving therapy, mastectomy) resulted in different overall survival, distant metastasis-free survival, and locoregional recurrence-free survival rates for the various molecular breast cancer subtypes. Summary Background Data:Molecular gene expression profiling has been proposed as a new classification and prognostication system for breast cancer. Current recommendation for local-regional treatment of breast cancer is based on traditional clinicopathologic variables. Methods:Retrospective analysis of 372 breast cancer cases with assessable immunohistochemical data for ER, PR, and Her-2/neu receptor status, diagnosed from 1998 to 2005. Molecular subtypes analyzed were luminal A, luminal B, basal like, and Her-2/neu. Results:No substantial difference was noted in overall survival, and locoregional recurrence rate between the local-regional treatment modalities as a function of the molecular breast cancer subtypes. The basal cell-like subtype was an independent predictor of a poorer overall survival (hazard ratio [HR] = 2.52, 95% confidence interval [CI] 1.28–4.97, P < 0.01) and a shorter distant metastasis-free survival time (HR = 3.61, 95% CI 1.27–10.2, P < 0.01), and showed a tendency toward statistical significance as an independent predictor of locoregional recurrence (HR = 3.57, 95% CI 0.93–13.6, P = 0.06). Conclusions:The basal cell-like subtype is associated with a worse prognosis, a higher incidence of distant metastasis, and may be more prone to local recurrence when managed with breast-conserving therapy.

An Exploratory Analysis of Fear of Recurrence among African-American Breast Cancer Survivors

BackgroundFear of recurrence (FOR) is a psychological concern that has been studied extensively in cancer survivors but has not been adequately examined in African-American breast cancer survivors.PurposeThis exploratory study describes the extent and nature of FOR in African-American breast cancer survivors. FOR is examined in relation to socio-demographic characteristics, treatment-related characteristics, psychological distress, and quality of life (QOL).MethodsParticipants completed questionnaires assessing FOR, psychological distress, QOL, and demographic and treatment characteristics. Pearson r correlations, t tests, and ANOVAs were used to determine the association between FOR and demographic and treatment-related characteristics. Hierarchical multiple regression models were performed to investigate the degree to which FOR dimensions account for the variance in QOL and psychological distress.ResultsFifty-one African-American breast cancer survivors participated in this study. The mean age of participants was 64.24 (SD = 12.3). Overall fears as well as concerns about death and health were rated as low to moderate. Role worries and womanhood worries were very low. Inverse relationships were observed between age and FOR dimensions. FOR was positively correlated with measures of psychological distress and negatively correlated with QOL. FOR significantly accounted for a portion of the variance in QOL and distress after controlling for other variables.ConclusionsThis study suggests that African-American women in this sample demonstrated some degree of FOR. Results indicate that FOR among African-American breast cancer survivors decreases with age and time since diagnosis and co-occurs with psychological distress as well as diminished quality of life.

Racial Disparity in Surgical Mortality after Major Hepatectomy

BACKGROUND The relationship between surgical mortality and race has not been studied for major hepatectomy. We sought to quantify and explore the nature of racial disparities in surgical mortality after major hepatectomy in a nationally representative cohort of patients. STUDY DESIGN We conducted a retrospective cohort study using data from the Nationwide Inpatient Sample (1998 to 2005). Adult patients undergoing major hepatectomy within 1 day of nontrauma admission were included. Logistic regression models were used to assess the variation of in-hospital mortality by race after adjustment for other risk factors. RESULTS The study cohort consisted of 3,552 observations representing 17,794 patients undergoing major hepatectomy. Unadjusted analyses revealed that African-American patients had a two-fold increased odds of surgical mortality (odds ratio 2.22, 95% CI 1.38 to 3.57) relative to Caucasians. Even after adjustment for other risk factors, African Americans had a two-fold increased odds of surgical mortality (odds ratio 2.15, 95% CI 1.28 to 3.61) relative to Caucasians. Stratified analyses restricting the cohort to patients without comorbidities, those with neoplasms, those with private insurance, or those treated at high-volume hospitals all demonstrated racial disparities in surgical mortality. CONCLUSIONS In-hospital mortality after major hepatectomy varies substantially by race. After adjustment for potential confounders, African-American patients have two-fold higher population-level odds of surgical mortality than Caucasian patients do. Our analyses suggest that clinical factors, insurance status, and hospital factors do not account for these differences. Additional studies to clarify the nature of this disparity and identify targets for intervention are warranted.

Understanding sleep disturbances in African-American breast cancer survivors: A pilot study

The goals of this study were (i) to report the prevalence and nature of sleep disturbances, as determined by clinically significant insomnia symptoms, in a sample of African‐American breast cancer survivors; (ii) to assess the extent to which intrusive thoughts about breast cancer and fear of recurrence contributes to insomnia symptoms; and (iii) to assess the extent to which insomnia symptoms contribute to fatigue.

Features Associated with Successful Recruitment of Diverse Patients onto Cancer Clinical Trials: Report from the American College of Surgeons Oncology Group

BackgroundThe clinical trials mechanism of standardized treatment and follow-up for cancer patients with similar stages and patterns of disease is the most powerful approach available for evaluating the efficacy of novel therapies, and clinical trial participation should protect against delivery of care variations associated with racial/ethnic identity and/or socioeconomic status. Unfortunately, disparities in clinical trial accrual persist, with African Americans (AA) and Hispanic/Latino Americans (HA) underrepresented in most studies.Study DesignWe evaluated the accrual patterns for 10 clinical trials conducted by the American College of Surgeons Oncology Group (ACOSOG) 1999–2009, and analyzed results by race/ethnicity as well as by study design.ResultsEight of 10 protocols were successful in recruiting AA and/or HA participants; three of four randomized trials were successful. Features that were present among all of the successfully recruiting protocols were: (1) studies designed to recruit patients with regional or advanced-stage disease (2 of 2 protocols); and (2) studies that involved some investigational systemic therapy (3 of 3 protocols).DiscussionAA and HA cancer patients can be successfully accrued onto randomized clinical trials, but study design affects recruitment patterns. Increased socioeconomic disadvantages observed within minority-ethnicity communities results in barriers to screening and more advanced cancer stage distribution. Improving cancer early detection is critical in the effort to eliminate outcome disparities but existing differences in disease burden results in diminished eligibility for early-stage cancer clinical trials among minority-ethnicity patients.

The Number of Lymph Nodes Examined Debate in Colon Cancer: How Much is Enough?

BACKGROUND Much debate exists over the significance of the number of lymph nodes (LN) examined after colon resection. MATERIALS AND METHODS The Surveillance, Epidemiology and End Results (SEER) database was queried for patients who presented with colonic adenocarcinoma. Multiple Cox proportional hazard regressions were run using successive LN cut-offs (6-26), first controlling for and then stratifying by T-stage. This was repeated in subsets of patients delineated by LN status. Additional variables controlled for in every regression were age, gender, ethnicity, marital status, number of positive LN, grade, metastases, and extent of surgery. After each regression, a Harrells C statistic and an Akaikes information criterion (AIC) were performed to test the predictive capacity and fit of the model, respectively. RESULTS 128,071 patients met selection criteria. The highest Harrells C statistics among all patients were the cutoffs at 14 LN and 15 LN. Between those, the AIC shows that the cutoff at 15 LN fit the data more closely than the 14 LN cutoff. The models with the best predictive ability and best fit by T-stage were T1, 14 LN; T2, 10 LN; T3, 10 LN; T4, 12 LN. CONCLUSIONS Using a population-based dataset, we show the optimal number of LN examined is dependent upon the patients tumor stage. Across all T-stages, the highest optimal number of LN resected was 15. Since it is possible to estimate but not perfectly predict the stage of a patients tumor preoperatively, we believe the recommendation should be based on the most conservative measure.