Publications

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    ABSTRACT: Evidence suggests superiority of breast conserving surgery (BCS) plus radiation over mastectomy alone for treatment of early stage breast cancer. Whether the superiority of BCS plus radiation is related to the surgical approach itself or to the addition of adjuvant radiation therapy following BCS remains unclear. We conducted a retrospective cohort study of women with breast cancer diagnosed from 1994-2012. Data regarding patient and tumor characteristics and treatment specifics were captured electronically. Kaplan-Meier survival analyses were performed with inverse probability of treatment weighting to reduce selection bias effects in surgical assignment. Data from 5335 women were included, of which two-thirds had BCS and one-third had mastectomy. Surgical decision trends changed over time with more women undergoing mastectomy in recent years. Women who underwent BCS versus mastectomy differed significantly regarding age, cancer stage/grade, adjuvant radiation, chemotherapy, and endocrine treatment. Overall survival was similar for BCS and mastectomy. When BCS plus radiation was compared to mastectomy alone, 3-, 5-, and 10-year overall survival was 96.5 vs 93.4%, 92.9 vs 88.3% and 80.9 vs 67.2%, respectively. These analyses suggest that survival benefit is not related only to the surgery itself, but that the prognostic advantage of BCS plus radiation over mastectomy may also be related to the addition of adjuvant radiation therapy. This conclusion requires prospective confirmation in randomized trials. © 2014 Marshfield Clinic.
    Clinical medicine & research. 12/2014;
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    ABSTRACT: To evaluate the ability of the McGill Brisbane Symptom Score (MBSS) to predict survival in resectable pancreatic head adenocarcinoma (PHA) patients.
    World journal of gastroenterology : WJG. 09/2014; 20(34):12226-32.
  • Adedayo A Onitilo, Jessica M Engel, Rachel V Stankowski
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    ABSTRACT: Before the advent of the human epidermal growth factor receptor 2 (HER2)-targeted monoclonal antibody trastuzumab, HER2-positive breast cancers were difficult to treat and had a poor prognosis. Adjuvant trastuzumab is now an important part of the treatment regimen for many women with HER2-positive breast cancer and has undoubtedly resulted in a significant improvement in prognosis, but it is associated with a risk for cardiotoxicity. In this review, we describe the prevalence, patient characteristics, and risk factors for cardiotoxicity associated with use of adjuvant trastuzumab. Understanding risk factors for trastuzumab-induced cardiotoxicity and appropriate patient monitoring during trastuzumab treatment allows for safe and effective use of this important adjuvant therapy.
    Therapeutic advances in drug safety. 08/2014; 5(4):154-66.
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    ABSTRACT: Routine mammography screening and early detection are important prognostic indicators for breast cancer. Geographical and seasonal barriers to mammography services and relationship to breast cancer stage at diagnosis were examined.
    Rural and remote health 07/2014; 14(3):2738. · 0.98 Impact Factor
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    ABSTRACT: Context.-The results of studies among patients with antithrombin deficiency have suggested that the use of warfarin will increase the level of antithrombin. Objective.-To reevaluate the effect of warfarin on antithrombin levels using an automated amidolytic method in current use. Design.-Antithrombin levels were measured in patients who were receiving warfarin for atrial fibrillation and were compared with antithrombin levels in preoperative patients who had not received warfarin. Results.-Patients receiving warfarin had a mean antithrombin level of 100.40% (range, 81%-153%). Patients not receiving warfarin had a mean antithrombin level of 99.97% (range, 79%-120%). The Student t test was not significant for a difference between the mean antithrombin levels of the 2 populations. Conclusions.-The use of warfarin does not increase the level of antithrombin in patients receiving the drug.
    Archives of pathology & laboratory medicine 07/2014; 138(7):967-968. · 2.78 Impact Factor
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    ABSTRACT: We developed an algorithm for the identification of patients with type 2 diabetes and ascertainment of the date of diabetes onset for examination of the temporal relationship between diabetes and cancer using data in the electronic medical record (EMR).
    BMC Medical Informatics and Decision Making 05/2014; 14(1):38. · 1.60 Impact Factor
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    ABSTRACT: Manuscript peer review is essential for ensuring accountability to all involved in the publication process, including authors, journals, and readers. Lack of consensus regarding what constitutes an accountable manuscript peer review process has resulted in varying practices from one journal to the next. Currently, reviewers are asked to make global judgments about various aspects of a paper for review irrespective of whether guided by a review checklist or not, and several studies have documented gross disagreement between reviewers of the same manuscript. We have previously proposed that the solution may be to direct reviewers to concrete items that do not require global judgments but rather provide a specific choice, along with referee justification for such choices. This study evaluated use of such a system via an international survey of health care professionals who had recently reviewed a health care--related manuscript. Results suggest that use of such a peer review system by reviewers does indeed improve interreviewer agreement, and thus, has the potential to support more consistent and effective peer review, if introduced into journal processes for peer review.
    Accountability in Research Policies and Quality Assurance 03/2014; 21(2):109-121.
  • Adedayo A Onitilo
    Clinical Medicine &amp Research 02/2014;
  • Sabo Tanimu, Rafiullah, Jeffrey Resnick, Adedayo A Onitilo
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    ABSTRACT: Oesophageal papillomatosis is a very rare entity, with only 10 cases (including ours) reported in the literature. We report a 51-year-old man with a 25-year history of dysphagia with solids and liquids who failed a trial of proton pump inhibitors and fluticasone. His initial endoscopy revealed a viliform mass with dense eosinophilic infiltrate without neoplasia. Endoscopic ultrasound examination revealed a 4×1.6×0.7 cm mucosal hemicircumferential lesion without regional adenopathy. Pathological findings from the oesophagectomy specimen confirmed oesophageal papillomatosis with no malignancy. Surveillance endoscopy 4 months later revealed the lesion had increased in size. Additional ablative therapies failed, and the patient underwent oesophagectomy. Surveillance CT of the chest and abdomen at 3 months and oesophagogastroduodenoscopy at 6 months were negative. This case illustrates that oesophageal squamous papillomatosis not amenable to medical therapy requires surgical treatment.
    Case Reports 01/2014; 2014(apr30_2).
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    ABSTRACT: Epidermal growth factor receptor (EGFR) inhibitors are approved for treating metastatic colorectal cancer (CRC); KRAS mutation testing is recommended prior to treatment. We conducted a non-inferiority analysis to examine whether KRAS testing has impacted survival in CRC patients. We included 1186 metastatic CRC cases from seven health plans. A cutpoint of July, 2008, was used to define two KRAS testing time period groups: "pre-testing" (n = 760 cases) and "post-testing" (n = 426 cases). Overall survival (OS) was estimated, and the difference in median OS between the groups was calculated. The lower bound of the one-sided 95% confidence interval (CI) for the difference in survival was used to test the null hypothesis of post-testing inferiority. Multivariable Cox regression models were constructed to adjust for covariates. The median unadjusted OS was 15.4 months (95% CI: 14.0-17.5) and 12.8 months (95% CI: 10.0-15.2) in the pre- and post-testing groups, respectively. The OS difference was -2.6 months with one-sided 95% lower confidence bound of -5.13 months, which was less than the non-inferiority margin (-5.0 months, unadjusted p = 0.06), leading to a failure to reject inferiority of OS in the post-testing period. In contrast, in the adjusted analysis, OS non-inferiority was identified in the post-testing period (p = 0.001). Sensitivity analyses using cutpoints before and after July, 2008, also met the criteria for non-inferiority. Implementation of KRAS testing did not influence CRC OS. Our data support the use of KRAS testing to guide administration of EGFR inhibitors for treatment of metastatic CRC without diminished OS.
    PLoS ONE 01/2014; 9(5):e94977. · 3.53 Impact Factor
  • Rafiullah, Sabo Tanimu, Adedayo A Onitilo
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    ABSTRACT: Gangliocytic paragangliomas are rare neuroendocrine tumours residing in the gastrointestinal tract, most commonly the periampullary region. Most are benign tumours with a low malignancy rate. We report a 50-year-old man who presented with acute onset of left-upper quadrant abdominal pain with radiation to the back. An intraluminal mass at the junction of the duodenum with normal pancreatic/hepatic parenchyma was discovered on abdominal CT. Following upper endoscopy and MRI revealing a periampullary lesion, fine-needle aspiration and biopsies were. Immunohistochemistry was positive for synaptophysin and S100HU, consistent with gangliocytic paraganglioma. The benign nature of this tumour and unique anatomy of a separate opening of the pancreatic and common bile ducts led to transduodenal excision with sphincteroplasty, thereby avoiding extensive surgery. Surveillance CT every 6 months and upper endoscopy initially every 6 months (now yearly) revealed no evidence of endoscopic or histological recurrence at 3 years follow-up.
    BMJ case reports. 01/2014; 2014.
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    ABSTRACT: Breast cancer is the most common cancer amongst women in the United States and around the world. Although widespread use of adjuvant chemotherapeutic and hormonal agents has improved mortality from breast cancer, it remains challenging to determine on an individual basis who will benefit from such treatments and who will be likely to encounter toxicities. With the rising costs of healthcare and the introduction of new targeted therapies, use of biomarkers has emerged as a method of assisting with breast cancer diagnosis, prognosis, prediction of therapeutic response, and surveillance of disease during and after treatment. In the following review, prognostic and therapeutic biomarkers, their utility in the management of patients with breast cancer, and current recommendations regarding their clinical use will be discussed.
    Current pharmaceutical design 11/2013; · 4.41 Impact Factor
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    Journal of the American College of Surgeons 11/2013; 217(5):960-2. · 4.50 Impact Factor
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    ABSTRACT: An Australian state database was used to test the validity of the Quantitative tumor/node/metastasis (QTNM) staging system for assessing prognosis of differentiated thyroid cancer (DTC) on the basis of four variables quantified at diagnosis (histopathology, age, node involvement, and tumor size). Using the Queensland Cancer Registry (QCR), we identified 788 cases of DTC diagnosed from 1982 to 2006 with complete staging information. Causes of death were ascertained by linking the QCR database with the Australian National Death Index. Subjects were staged according to AJCC TNM 7th edition and QTNM, and cancer-specific survival (CSS) was calculated by the Kaplan-Meier method. Cancer-specific mortality was observed in 22 (2.8 %) patients, with 10-year CSS for the cohort of 97.0 % at a median follow-up of 262.8 months. QTNM stage specific cancer survival at 10 years was 99.6, 97.0, and 78.6 % for low-, intermediate-, and high-risk groups, respectively. This was comparable to the original US dataset in which the QTNM was initially studied, and it fared better at discriminating survival than the standard TNM system, where there was overlap in survival between stages. The current study validates the QTNM system in an Australian cohort and shows at least equivalent discriminatory capacity to the current TNM staging system. The QTNM utilized prognostic variables of significance to produce an optimal three-stage stratification scheme. Given, its advantage in clearly discriminating between prognostic groups, clinical relevance and simplicity of use, we recommend that TNM be replaced with QTNM for risk stratification for both recurrence and CSS.
    Endocrine 10/2013; · 3.53 Impact Factor
  • Jessica Engel, Darlene Plank, Adedayo Onitilo
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    ABSTRACT: Background/Aims Advanced pancreatic cancer has a poor overall prognosis. Fear, anxiety, sadness, and uncertainty are common responses felt by many who are diagnosed with this unfortunate disease, as well as feeling a variety of discomforts related to the cancer itself. Faced with limited time, many hope for longevity while maintaining as good a quality of life as possible. After diagnosis, a multitude of considerations are thought to be essential and beneficial for the patient, caregivers, and medical care providers, including addressing advanced illness planning related to coping, decision-making, cancer treatment, symptom management, and end-of-life care. While the recognition of those considerations is thought to contribute to improved quality of care, often these topics or related interventions are not fully addressed or implemented, potentially leading to a less than ideal experience for the patient with advanced pancreatic cancer. The goal of this study is to evaluate care patterns for advanced pancreatic cancer, address completeness of care based on current standards and guidelines, and provide recommendations for improved overall care and support. Methods Data from the Marshfield Clinic electronic medical record and cancer registry will be electronically and manually abstracted. All patients diagnosed with stage IV pancreatic cancer from 2010-2012 will be included to reflect current care patterns. Data will include patient and cancer characteristics; cancer treatment; presence and management of significant symptoms; number and reason for hospitalization(s); whether or not prognosis and treatment options were discussed; and whether palliative/hospice care and other supportive care referrals were offered or occurred. Comprehensive review of the literature will be undertaken to compile present standards and guidelines regarding advanced cancer care. Results Planned analyses include summary of patient and cancer characteristics, including survival; and determination of variability and commonalities in patient care coordination and utilization of supportive services. Conclusions Understanding the met and unmet needs of patients with advanced pancreatic cancer will lead to improved quality of care and quality of life. Results of this study will be used to write a guideline for improved care and support.
    Clinical Medicine &amp Research 09/2013; 11(3):133.
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    ABSTRACT: Background/Aims Early diagnosis of breast cancer is an important prognostic indicator and missed mammograms represent missed opportunities for earlier diagnosis. Geographical access to mammography services is an important factor in mammography screening. In rural regions, mammography access can be problematic and longer travel distance has been shown to adversely affect early breast cancer detection in rural populations, although results are mixed. Recent advances in geographic information systems (GIS) technology allows for more accurate determination of point distance and travel time via road networks. The goal of the present study was to utilize modern GIS technology to determine the association between geographic proximity to mammogram centers and stage of breast cancer at diagnosis. Methods Female patients with an initial diagnosis of primary breast cancer at the Marshfield Clinic between January 1, 2002 and December 30, 2008 were identified electronically through the Marshfield Clinic/St. Joseph's Hospital cancer registry. Patients were classified by stage of breast cancer and analyzed to determine whether a correlation existed between stage and distance to closest facility, distance to visited facility, and rural or urban address location. ESRI ArcGIS Desktop version 10.0, ArcInfo license, Business Analyst extension, and StreetMap Premium using data from TeleAtlas 2010 were used to geocode point features and the ArcGIS Geocoding toolbar, Review/Rematch Addresses tool was used to substantiate the results. Results A total of 1,368 patients with breast cancer was analyzed. A trend of increased travel time to nearest facility with increasing stage at diagnosis was observed (P = 0.0643), where median travel time was 17.1 minutes for stage 0 breast cancer and 23.9 min for stage 4 breast cancer. Significantly fewer mammograms were performed in the winter months (November through February) and the difference was particularly striking for patients living 30 or more miles from a mammography center (P = 0.0448). Conclusions Using modern GIS technology, we showed that travel time affects mammogram utilization and thus stage at breast cancer diagnosis in the Marshfield Clinic service area. In rural areas, travel time and seasonal road conditions may impact on decisions to undergo mammography screening.
    Clinical Medicine &amp Research 09/2013; 11(3):131.
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    ABSTRACT: Type 2 diabetes mellitus is characterized by prolonged hyperinsulinemia, insulin resistance, and progressive hyperglycemia. Disease management relies on glycemic control through diet, exercise, and pharmacological intervention. The goal of the present study was to examine the effects of glycemic control and the use of glucose-lowering medication on the risk of breast, prostate, and colon cancer. Patients diagnosed with type 2 diabetes mellitus (N=9486) between 1 January 1995 and 31 December 2009 were identified and data on glycemic control (hemoglobin A1c, glucose), glucose-lowering medication use (insulin, metformin, sulfonylurea), age, BMI, date of diabetes diagnosis, insurance status, comorbidities, smoking history, location of residence, and cancer diagnoses were electronically abstracted. Cox proportional hazards regression modeling was used to examine the relationship between glycemic control, including medication use, and cancer risk. The results varied by cancer type and medication exposure. There was no association between glycemic control and breast or colon cancer; however, prostate cancer risk was significantly higher with better glycemic control (hemoglobin A1c≤7.0%). Insulin use was associated with increased colon cancer incidence in women, but not with colon cancer in men or breast or prostate cancer risk. Metformin exposure was associated with reduced breast and prostate cancer incidence, but had no association with colon cancer risk. Sulfonylurea exposure was not associated with risk of any type of cancer. The data reported here support hyperinsulinemia, rather than hyperglycemia, as a major diabetes-related factor associated with increased risk of breast and colon cancer. In contrast, hyperglycemia appears to be protective in the case of prostate cancer.
    European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 08/2013; · 2.21 Impact Factor
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    ABSTRACT: OBJECTIVE. Missed mammograms represent missed opportunities for earlier breast cancer diagnosis. The purposes of this study were to identify patient characteristics associated with missed mammograms and to examine the association between missed mammograms and breast cancer stage at diagnosis. MATERIALS AND METHODS. Mammography frequency and cancer stage were retrospectively examined in cases of primary breast cancer diagnosed at our clinic from 2002 to 2008. RESULTS. Regardless of age (median, 62.7 years), women who underwent mammography were more likely to have early-stage (stage 0-II) breast cancer at diagnosis than were those who did not undergo mammography (p < 0.001). Similarly, the number of mammographic examinations in the 5 years before diagnosis was inversely related to stage: 57.3% (94/164) of late-stage cancers were diagnosed in women missing their last five annual mammograms. In a multivariate analysis, family history of breast cancer was most predictive of undergoing mammography (odds ratio, 3.492; 95% CI, 2.616-4.662; p < 0.0001) followed by number of medical encounters (odds ratio, 1.022; 95% CI, 1.017-1.027; p < 0.0001). Time to travel to the nearest mammography center was also predictive of missing mammograms: Each additional minute of travel time decreased the odds of undergoing at least one mammographic examination in the 5 years before cancer diagnosis (odds ratio, 0.990; 95% CI, 0.986-0.993; p < 0.0001). CONCLUSION. Missing a mammogram, even in the year before a breast cancer diagnosis, increases the chance of a cancer diagnosis at a later stage. Interventions to encourage use of mammography may be of particular benefit to women most likely to miss mammograms, including those with no family history of breast cancer, fewer encounters with the health care system, and greater travel distance to the mammography center.
    American Journal of Roentgenology 08/2013; · 2.90 Impact Factor
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    ABSTRACT: Objective Diabetes is more common in cancer survivors than in the general population. The objective of the present study was to determine cancer frequency in a cohort of patients with diabetes and to examine demographic, clinical, and quality of life differences between cancer survivors and their cancer-free peers to inform better individualized care.Methods Self-reported survey data from 3,466 registrants with type 2 diabetes from Australia's National Diabetes Services Scheme (NDSS) were analyzed to compare relevant variables between cancer survivors and cancer-free patients. Analyses were focused on breast and prostate cancer to reflect the most common cancers in women and men, respectively.ResultsFive percent of diabetic women reported a history of breast cancer and 4.2% of men reported a history of prostate cancer. Diabetic patients with a history of breast or prostate cancer were older at time of survey and diabetes diagnosis, less likely to report metformin use (women), and more likely to have two or more comorbidities than their cancer-free peers. More diabetic prostate cancer survivors also reported problems with mobility and performing usual tasks. However, cancer-free diabetic subjects reported a lower diabetes-dependent quality of life than diabetic cancer survivors. There was no association between cancer survivorship and duration of diabetes, indices of glycemic control, obesity, or diabetic complications.Conclusions Cancer survivors comprise a significant minority of diabetic patients that are particularly vulnerable and may benefit from interventions to increase screening and treatment of other comorbidities and promote a healthy lifestyle.
    Clinical Medicine &amp Research 05/2013;
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    ABSTRACT: Background Diagnosis and duration of type 2 diabetes mellitus (DM) appears to be associated with decreased prostate cancer risk. Limitations of previous studies include methods of subject selection and accurate definition of DM diagnosis. We examined the temporal relationship between DM and prostate cancer risk exploring the period of greatest risk starting from the prediabetic to the post-diabetic period using clinical and administrative data to accurately define the date of DM diagnosis.Methods We identified 5,813 men who developed DM between January 1, 1995 and December 31, 2009 (reference date, date of DM onset or matched date for non-diabetic cohort) and 28,019 non-diabetic men matched by age, smoking history, residence, and reference date. Prostate cancer incidence before and after the reference date was assessed using Cox regression modeling adjusted for matching variables, body mass index, insurance status, and comorbidities. Primary outcomes included hazard ratio (HR) and number needed to be exposed to DM for one additional person to be harmed (NNEH) or benefit (NNEB) with respect to prostate cancer risk.ResultsAfter full adjustment, the HR for prostate cancer before DM diagnosis was 0.96 (95% CI 0.85 1.08; P=0.4752), and the NNEB was 974 at DM diagnosis. After the reference date, the fully-adjusted HR for prostate cancer in diabetic men was 0.84 (95% CI 0.72 0.97, P=0.0167), and the NNEB 3 years after DM onset was 425. The NNEB continued to decrease over time, reaching 63 at 15 years after DM onset, suggesting an increasing protective effect of DM on prostate cancer risk over time. No significant difference between the diabetic and non-diabetic cohort was found prior to reference date.Conclusion Prostate cancer risk is not reduced in pre-diabetic men but decreases after DM diagnosis and the protective effect of DM onset on prostate cancer risk increases with DM duration.
    Clinical Medicine &amp Research 05/2013;

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