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1.  Adrenal Nodular Hyperplasia in Hereditary Leiomyomatosis and Renal Cell Cancer 
The Journal of urology  2012;189(2):430-435.
Purpose
Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is characterized by cutaneous leiomyomas, uterine fibroids, and aggressive papillary renal cell carcinoma (RCC). A number of our HLRCC patients were found to have atypical adrenal nodules and which were further evaluated to determine if these adrenal nodules were associated with HLRCC.
Methods
HLRCC patients underwent a comprehensive clinical and genetic evaluation. Clinical presentation, anatomic and functional imaging, endocrine evaluation, pathologic examination and the results from germline mutation testing were reviewed.
Results
Twenty of 255 HLRCC patients (7.8%) were found to have primary adrenal lesions. Among these, three were found to have bilateral adrenal lesions and four were found to have multiple nodules. Two patients had ACTH-independent hypercortisolism. A total of 27 adrenal lesions were evaluated. The imaging characteristics of five (18.5%) of these lesions were not consistent with adenoma by non-contrast CT criteria. PET imaging was positive in 7 of 10 cases (70%). Twelve nodules were surgically resected from ten adrenal glands. Pathologic examination revealed macronodular adrenal hyperplasia in all specimens.
Conclusions
Unilateral and bilateral adrenal nodular hyperplasia was detected in a subset of patients affected with HLRCC. A functional endocrine evaluation is recommended when an adrenal lesion is discovered. Imaging frequently demonstrates lesions that are not typical of adenomas and PET imaging may be positive. To date, no patient has been found to have adrenal malignancy and active surveillance of HLRCC adrenal nodules appears justified.
doi:10.1016/j.juro.2012.07.139
PMCID: PMC4435969  PMID: 22982371
HLRCC; kidney cancer; adrenal nodule; fumarate hydratase
2.  Alcohol quantity and type on risk of recurrent gout attacks: An internet-based case-crossover study 
The American journal of medicine  2014;127(4):311-318.
Objectives
Although beer and liquor have been associated with risk of incident gout, wine has not. Yet anecdotally, wine is thought to trigger gout attacks. Further, how much alcohol intake is needed to increase the risk of gout attack is not known. We examined the quantity and type of alcohol consumed on risk of recurrent gout attacks.
Methods
We conducted a prospective internet-based case-crossover study in the United States among participants with gout and who had at least one attack during the one year of follow-up. We evaluated the association of alcohol intake over the prior 24 hours as well as the type of alcoholic beverage with risk of recurrent gout attack, adjusting for potential time-varying confounders.
Results
This study included 724 participants with gout (78% men, mean age 54 years). There was a significant dose-response relationship between amount of alcohol consumption and risk of recurrent gout attacks (p<0.001 for trend). The risk of recurrent gout attack was 1.36 (95% CI: 1.00 to 1.88) and 1.51 (95% CI: 1.09 to 2.09) times higher for >1–2 and >2–4 alcoholic beverages, respectively, compared with no alcohol consumption in the prior 24 hours. Consuming wine, beer, or liquor, was each associated with an increased risk of gout attack.
Conclusions
Episodic alcohol consumption, regardless of type of alcoholic beverage, was associated with an increased risk of recurrent gout attacks, including potentially with moderate amounts. Persons with gout should limit alcohol intake of all types to reduce the risk of recurrent gout attacks.
doi:10.1016/j.amjmed.2013.12.019
PMCID: PMC3991555  PMID: 24440541
gout attacks; alcohol; triggers; internet; case-crossover
3.  Nocturnal Risk of Gout Attacks 
Objective
Several plausible mechanisms and anecdotal descriptions suggest that gout attacks often occur at night, although there are no scientific data supporting this. We undertook this study to evaluate the hypothesis that gout attacks occur more frequently at night.
Methods
We conducted a case-crossover study to examine the risk of acute gout attacks in relation to the time of the day. Gout patients were prospectively recruited and followed up via the internet for 1 year. Participants were asked about the following information concerning their gout attacks: the date and hour of attack onset, symptoms and signs, medication use, and purported risk factors during the 24- and 48-hour periods prior to the gout attack. We calculated the odds ratios (ORs) of gout attacks (with 95% confidence intervals [95% CIs]) according to three 8-hour time blocks of the day (i.e., 12:00 am to 7:59 am, 8:00 am to 3:59 pm [reference], and 4:00 pm to 11:59 pm) using conditional logistic regression.
Results
Our study included 724 gout patients who experienced a total of 1,433 attacks (733, 310, and 390 attacks during the first, second, and third 8-hour time blocks, respectively) over 1 year. The risk of gout flares in the 8-hour overnight time block (12:00 am to 7:59 am) was 2.36 times higher than in the daytime (8:00 am to 3:59 pm) (OR 2.36 [95% CI 2.05–2.73]). The corresponding OR in the evening (4:00 pm to 11:59 pm) was 1.26 (95% CI 1.07–1.48). These associations persisted among those with no alcohol use and in the lowest quintile of purine intake in the 24 hours prior to attack onset. Furthermore, these associations persisted in subgroups according to sex, age group, obesity status, diuretic use, and use of allopurinol, colchicine, and nonsteroidal antiinflammatory drugs.
Conclusion
These findings provide the first prospective evidence that the risk of gout attacks during the night and early morning is 2.4 times higher than in the daytime. Further, these data support the purported mechanisms and historical descriptions of the nocturnal onset of gout attacks and may have implications for antigout prophylactic measures.
doi:10.1002/art.38917
PMCID: PMC4360969  PMID: 25504842
4.  Goodness gracious great balls of fire 
BMJ Case Reports  2013;2013:bcr2012007903.
doi:10.1136/bcr-2012-007903
PMCID: PMC3618754  PMID: 23505271
5.  Clinical outcomes with bevacizumab-containing and non-bevacizumab–containing regimens in patients with recurrent glioblastoma from US community practices 
Journal of Neuro-Oncology  2015;122(3):595-605.
This analysis evaluated the efficacy and safety of bevacizumab as monotherapy and with irinotecan for recurrent glioblastoma in community-based practices. Adult patients with bevacizumab-naive, recurrent glioblastoma initiating second-line treatment (July 2006–June 2010) were identified using McKesson Specialty Health/US Oncology Network health records. Overall (OS) and progression-free survival (PFS) estimates were analyzed through July 2011 and compared for bevacizumab and non-bevacizumab regimens using the log-rank test. An adjusted Cox proportional hazards model assessed the effects of patient and treatment characteristics on outcomes. The analysis identified 159 patients initiating second-line treatment with a bevacizumab-monotherapy (n = 57), bevacizumab-combination (n = 79), or non-bevacizumab (n = 23) regimen. Patient characteristics were generally similar across groups. In the Cox analyses, OS (hazard ratio [HR] 0.51 [95 % confidence interval (CI) 0.31–0.82]; univariate medians: 8.86 vs. 5.19 months) was significantly longer with bevacizumab-containing regimens. Median PFS was longer with bevacizumab-containing regimens, but did not reach statistical significance (HR 0.64 [95 % CI 0.38–1.09]; univariate medians: 7.00 vs. 4.00 months). Analyses showed that each bevacizumab treatment group relative to non-bevacizumab had a reduced risk of death (bevacizumab-monotherapy regimen: HR 0.56 [95 % CI 0.31–1.03] and bevacizumab-combination regimen: HR 0.34 [95 % CI 0.21–0.68]). Patients receiving the bevacizumab-combination regimen trended toward longer OS and PFS than those receiving the bevacizumab-monotherapy regimen. Rates of bevacizumab-related toxicities were consistent with clinical trial reports.
Electronic supplementary material
The online version of this article (doi:10.1007/s11060-015-1752-y) contains supplementary material, which is available to authorized users.
doi:10.1007/s11060-015-1752-y
PMCID: PMC4436682  PMID: 25773061
Bevacizumab; Recurrent glioblastoma; Community practice; Retrospective analysis
6.  18F-FDG PET/CT as a predictor of hereditary head and neck paragangliomas 
Background
Hereditary head and neck paragangliomas (HNPGLs) account for at least 35% of all HNPGLs, most commonly due to germline mutations in SDHx susceptibility genes. Several studies about sympathetic paragangliomas have shown that 18F-FDG PET/CT was not only able to detect and localize tumors, but also to characterize tumors (18F-FDG uptake being linked to SDHx mutations). However, the data concerning 18FFDG uptake specifically in HNPGLs have not been addressed. The aim of this study was to evaluate the relationship between 18F-FDG uptake and the SDHx mutation status in HNPGL patients.
Methods
18F-FDG PET/CT from sixty HNPGL patients were evaluated. For all lesions, we measured the maximum standardized uptake values (SUVmax), and the uptake ratio defined as HNPGL SUVmax over pulmonary artery trunk SUVmean (SUVratio). Tumor sizes were assessed on radiological studies.
Results
Sixty patients (53.3% with SDHx mutations) were evaluated for a total of 106 HNPGLs. HNPGLs SUVmax and SUVratio were highly dispersed (1.2-30.5 and 1.0-17.0 respectively). The HNPGL 18F-FDG uptake was significantly higher in SDHx versus sporadic tumors on both univariate and multivariate analysis (p=0.002). We developed two models for calculating the probability of a germline SDHx mutation. The first one, based on a per-lesion analysis, had an accuracy of 75.5%. The second model, based on a per-patient analysis, had an accuracy of 80.0%.
Conclusions
18F-FDG uptake in HNPGL is strongly dependent on patient genotype. Thus, the degree of 18F-FDG uptake in these tumors can be used clinically to help identify patients in whom SDHx mutations should be suspected.
doi:10.1111/eci.12239
PMCID: PMC3955826  PMID: 24422786
PET-CT; head and neck paraganglioma; fluorodeoxyglucose; hereditary cancer; radiopharmaceuticals; genetics
7.  Social Service Barriers Delay Care Among Women with Abnormal Cancer Screening 
ABSTRACT
BACKGROUND
Inequity in cancer outcomes for minorities and vulnerable populations has been linked to delays in cancer care that arise from barriers to accessing care. Social service barriers represent those obstacles related to meeting life’s most basic needs, like housing and income, which are often supported by public policy, regulation and services.
OBJECTIVE
To examine the association between social service barriers and timely diagnostic resolution after a cancer screening abnormality.
DESIGN
Secondary analysis of the intervention arm of Boston Patient Navigation Research Program (2007–2008) conducted across six urban community health centers. Subjects with no barriers, other barriers, and social service barriers were compared on their time to diagnostic resolution.
SUBJECTS
Women ≥ 18 years of age with a breast or cervical cancer screening abnormality.
MAIN MEASURES
Social service barriers included: income supports, housing and utilities, education and employment, and personal/family stability and safety. Time to event analyses compared across five groups: those with no barriers, one barrier (other), one barrier (social service), two or more barriers (all other), and two or more barriers (at least one social service).
KEY RESULTS
1,481 navigated women; 31 % Hispanic, 27 % Black, 32 % White; 37 % non-English speakers and 28 % had private health insurance. Eighty-eight women (6 %) had social service barriers. Compared to those without social service barriers, those with were more likely to be Hispanic, younger, have public/no health insurance, and have multiple barriers. Those with two or more barriers (at least one social service barrier), had the longest time to resolution compared to the other four groups (aHR resolution < 60 days = 0.27, ≥ 60 days = 0.37).
CONCLUSION
Vulnerable women with multiple barriers, when at least one is a social service barrier, have delays in care despite navigation. The impact of patient navigation may never be fully realized if social service barriers persist without being identified or addressed.
doi:10.1007/s11606-013-2615-x
PMCID: PMC3889949  PMID: 24197626
access to care; cancer; disparities; vulnerable populations
8.  Prediction of the location and size of the stomach using patient characteristics for retrospective radiation dose estimation following radiotherapy 
Physics in medicine and biology  2013;58(24):8739-8753.
Following cancer radiotherapy, reconstruction of doses to organs, other than the target organ, is of interest for retrospective health risk studies. Reliable estimation of doses to organs that may be partially within or fully outside the treatment field requires reliable knowledge of the location and size of the organs, e.g., the stomach, which is at risk from abdominal irradiation. The stomach location and size are known to be highly variable between individuals, but have been little studied. Moreover, for treatments conducted years ago, medical images of patients are usually not available in medical records to locate the stomach. In light of the poor information available to locate the stomach in historical dose reconstructions, the purpose of this work was to investigate the variability of stomach location and size among adult male patients and to develop prediction models for the stomach location and size using predictor variables generally available in medical records of radiotherapy patients treated in the past. To collect data on stomach size and position, we segmented the contours of the stomach and of the skeleton on contemporary Computed Tomography (CT) images for 30 male patients in supine position. The location and size of the stomach was found to depend on body mass index (BMI), ponderal index (PI), and age. For example, the anteroposterior dimension of the stomach was found to increase with increasing BMI (≈0.25 cm per kg/m2) whereas its craniocaudal dimension decreased with increasing PI (≈ −3.3 cm per kg/m3) and its transverse dimension increased with increasing PI (≈ 2.5 cm per kg/m3). Using the prediction models, we generated three dimensional computational stomach models from a deformable hybrid phantom for three patients of different BMI. Based on a typical radiotherapy treatment, we simulated radiotherapy treatments on the predicted stomach models and on the CT images of the corresponding patients. Those dose calculations demonstrated good agreement between predicted and actual stomachs compared with doses derived from a reference model of the body that might be used in the absence of individual CT scan data.
doi:10.1088/0031-9155/58/24/8739
PMCID: PMC4160803  PMID: 24301086
stomach; size and location; predictive models; radiation dose
9.  Increased Risk of Recurrent Gout Attacks with Hospitalization 
The American journal of medicine  2013;126(12):10.1016/j.amjmed.2013.06.026.
Background
While anecdotal evidence suggests that risk of recurrent gout attack increases with hospitalization, no study has formally tested this hypothesis.
Methods
We conducted an online case-crossover study of individuals with gout. We obtained information on gout attacks over a one-year period, including: onset date, symptoms and signs, medications, and exposure to potential risk factors, including hospitalization, during the 2-day hazard period prior to each gout attack. The same exposure information was also obtained over 2-day intercritical gout control periods. We performed conditional logistic regression to examine the relationship of hospitalization with recurrent gout attacks and whether such a relationship was modified by concomitant use of anti-gout medications.
Results
Of 724 participants (mean age 54.5 years, 78.5% male), 35 hospitalizations occurred during either a hazard or control period. The adjusted odds of gout attacks was increased 4-fold with hospitalization (OR 4.05, 95% confidence interval: 1.78–9.19) compared with no hospitalization. The effect of hospitalization tended to attenuate with use of allopurinol, colchicine, or NSAIDs, but not statistically significantly.
Conclusions
Our study confirmed that the risk of gout attacks increases among gout patients during hospitalization. Appropriate measures should be considered for prevention of gout attacks during hospitalization for patients with pre-existing gout.
doi:10.1016/j.amjmed.2013.06.026
PMCID: PMC3838663  PMID: 24054179
10.  Multi-tracer PET imaging of bone metastases from paraganglioma: peripheral halo of uptake on 18F-FLT PET mismatching with central uptake of 18F-FDOPA, 18F-Fdopamine, and 18F-FDG 
European journal of nuclear medicine and molecular imaging  2013;40(12):10.1007/s00259-013-2507-7.
doi:10.1007/s00259-013-2507-7
PMCID: PMC3840388  PMID: 23880966
pheochromocytoma and paraganglioma; bone metastases; PET/CT; 18F-fluorothymidine; 18F-fluorodeoxyglucose; cell proliferation
11.  99mTc-labeled Therapeutic Inhaled Amikacin Loaded Liposomes 
Journal of liposome research  2013;23(4):336-342.
The radiolabeling of the liposome surface can be a useful tool for in vivo tracking of therapeutic drug loaded liposomes. We investigated radiolabeling therapeutic drug (i.e., an antibiotic, amikacin) loaded liposomes with 99mTc, nebulization properties of 99mTc-labeled liposomal amikacin for inhalation (99mTc-LAI), and its stability by size exclusion low pressure liquid chromatography (LPLC). LAI was reacted with 99mTc using SnCl2 dissolved in ascorbic acid as a reducing agent for 10 min at room temperature. The labeled products were then purified by anion exchange resin. The purified 99mTc-LAI in 1.5% NaCl solution was incubated at 4oC to assess its stability by LPLC. The purified 99mTc-LAI was subjected to studies with a clinically used nebulizer (PARI eFlow®) and the Anderson Cascade Impactor (ACI). The use of ascorbic acid at 0.91 mM resulted in a quantitative labeling efficiency. The LPLC profile showed that the liposomal peak of LAI detected by a UV monitor at both 200 nm and 254 nm overlapped with the radioactivity peak of 99mTc-LAI, indicating that 99mTc-LAI is suitable for tracing LAI. The ACI study demonstrated that the aerosol droplet size distribution determined gravimetrically was similar to that determined by radioactivity. The liposome surface labeling method using SnCl2 in 0.91mM ascorbic acid produced 99mTc-LAI with a high labeling efficiency and stability that are adequate to evaluate the deposition and clearance of inhaled LAI in the lung by gamma scintigraphy.
doi:10.3109/08982104.2013.819889
PMCID: PMC4231483  PMID: 23879241
99mTc-labeled liposome-encapsulated amikacin; radiolabeling; size exclusion analysis
12.  Prevalence of Advanced Colorectal Neoplasia in Whites and Blacks Undergoing Screening Colonoscopy in a Safety Net Hospital 
Annals of internal medicine  2013;159(1):13-20.
Background
Blacks are more likely than whites to be diagnosed with colorectal cancer and die of their disease. The extent to which genetic or biologic factors versus disparities in screening rates explain this variance remains controversial.
Objective
To define the prevalence and location of presymptomatic advanced colorectal neoplasia (ACN) among whites and blacks undergoing screening colonoscopy controlling for other epidemiologic determinants of risk.
Design
Cross-sectional survey between March 22, 2005 and January 31, 2012.
Setting
Urban, open-access, academic, safety net hospital in Massachusetts.
Participants
Asymptomatic, average-risk whites (n=1172) and blacks (n=1681) 50 to 79 years of age presenting for screening colonoscopy.
Measurements
Adjusted prevalence and location of ACN, defined as a tubular adenoma ≥ 10 mm in size, any adenoma with villous features or high-grade dysplasia, any dysplastic serrated lesion, or invasive cancer.
Results
The prevalence of ACN was higher among whites than blacks (6.8% vs. 5.0%; P=0.039) but varied by sex (white versus black men, 9.3% vs. 5.7%; white vs. black women, 3.5% vs. 4.3%; P for interaction =0.034). After controlling for exposure to multiple risk factors, black men were 41% less likely than white men (adjusted odds ratio [aOR], 0.59; 95% confidence intervals [CI], 0.39–0.89) to have ACN; conversely, no significant differences were observed for women (aOR, 1.32; 95% CI, 0.73–2.40). Among individuals with ACN, blacks a higher percentage of proximal disease (52% vs. 39%) after adjustment for age and sex (P=0.055).
Limitations
Single institution study; inadequate statistical power for subgroup analyses; recall bias.
Conclusions
Black men are less likely than white men to have ACN at screening colonoscopy in a safety net health care setting. These findings suggest that disparities in access to screening and differential exposure to modifiable risk factors rather than genetic or biologic factors are largely responsible for the higher incidence of CRC among black men. Genetic or biologic factors, however may explain the predilection for proximal disease.
Primary Funding Source
National Cancer Institute
doi:10.7326/0003-4819-159-1-201307020-00004
PMCID: PMC4218749  PMID: 23817700
13.  Current and future trends in the anatomic and functional imaging of head and neck paragangliomas 
Seminars in nuclear medicine  2013;43(6):462-473.
Head and neck paragangliomas (HNPGLs) account for approximately 3% of all paragangliomas (PGLs). Most often, HNPGLs are benign, non-secreting, and slowly progressing. The initial physical examination and biochemical diagnosis usually adds very little to the proper diagnosis of these tumors and therefore, radiologists and nuclear medicine physicians play the pivotal role in providing the initial diagnosis, the locoregional staging, and the plan for detecting potential multicentric or metastatic lesions. Based on several current studies, the most accurate use of HNPGL-specific initial and subsequent imaging modalities must be guided by the knowledge of genetics and the specifically measured biochemical profile of these tumors for the proper management of these patients. Thus, this short review article presents the application of the most up-to-date anatomic and functional imaging approaches to HNPGLs tightly linked to the clinical management of these patients. Based on the most recent studies, 18F-FDOPA PET/CT has been shown to be a useful addition to anatomic imaging in the preoperative localization and molecular assessment of HNPGLs. It is estimated that the frequency of metabolically active PGLs on 18F-FDOPA PET/CT in this region is higher than 90%. 18F-FDG PET/CT should be reserved for patients with hereditary PGL syndromes. Imaging of somatostatin receptors using Octreoscan or 68Ga-labeled somatostatin analogs plays an important role for selecting patients for targeted radiation therapy.
This review also concludes that it is expected that in the near future, these patients will indeed benefit from new diagnostic approaches based on the identification of new targets by molecular profiling studies that will result in the development of novel PGL specific radiopharamceuticals.
doi:10.1053/j.semnuclmed.2013.06.005
PMCID: PMC3792493  PMID: 24094713
Positron emission tomography; computed tomography; paraganglioma; radiopharmaceuticals; genetics; head and neck
14.  Impact of Depression on the Intensity of Patient Navigation for Women with Abnormal Cancer Screenings 
Patient navigation is increasingly being used to support vulnerable patients to receive timely and quality medical care. We sought to understand whether patients with depression utilize additional patient navigation services after abnormal cancer screening. We compared depressed and non-depressed women using three different measures of intensity of patient navigation: number of patient-navigator encounters, encounter time, and number of unique barriers to care. The study population consisted of 1,455 women who received navigation after abnormal screening for breast or cervical cancer at one of six community health centers in Boston. Navigators spent a median of 60–75 minutes over one or two encounters per participant, with 49% of participants having one or more documented barrier to care. Depressed women did not differ in total numbers of encounters, encounter time, or unique barriers compared with non-depressed women. Our findings suggest that pre-existing depression does not predict which women will utilize additional navigation services.
doi:10.1353/hpu.2014.0045
PMCID: PMC4184058  PMID: 24509033
Patient navigation; depression; women’s health; cancer screening; navigation intensity
15.  Functional characterization of non-metastatic paraganglioma and pheochromocytoma by 18F-FDOPA PET: focus on missed lesions 
Clinical endocrinology  2013;79(2):170-177.
SUMMARY
Aims and methods
To evaluate the clinical value of 18F-fluorodihydroxyphenylalanine (18F-FDOPA) PET in relation to tumour localization and the patient’s genetic status in a large series of pheochromocytoma/paraganglioma (PHEO/PGL) patients and to discuss in detail false-negative results.
A retrospective study of PGL patients who were investigated with 18F-FDOPA PET or PET/CT imaging in two academic endocrine tumour centers was conducted (La Timone University Hospital, Marseilles, France and National Institutes of Health (NIH), Bethesda, MD, USA).
Results
One hundred sixteen patients (39.7% harboring germline mutations in known disease susceptibility genes) were evaluated for a total of 195 PHEO/PGL foci. 18F-FDOPA PET correctly detected 179 lesions (91.8%) in 107 patients (92.2%).
Lesion-based sensitivities for parasympathetic PGLs (head, neck, or anterior/middle thoracic ones), PHEOs, and extra-adrenal sympathetic (abdominal or posterior thoracic) PGLs were 98.2% [96.5% for Timone and 100% for NIH], 93.9% [93.8% and 93.9%], and 70.3% [47.1% and 90%], respectively (P<0.001).
Sympathetic (adrenal and extra-adrenal) SDHx-related PGLs were at a higher risk for negative 18F-FDOPA PET than non-SDHx-related PGLs (14/24 vs 0/62, respectively, p<0.001). By contrast, the risk of negative 18F-FDOPA PET was lower for parasympathetic PGLs regardless of the genetic background (1/90 in SDHx vs 1/19 in non-SDHx tumours, p= 0.32).
18F-FDOPA PET failed to detect 2 head and neck PGLs (HNPGL), likely due to their small size, while most missed sympathetic PGL were larger and may have exhibited a specific 18F-FDOPA-negative imaging phenotype. 18F-FDG PET detected all the missed sympathetic lesions.
Conclusions
18F-FDOPA PET appears to be a very sensitive functional imaging tool for HNPGL regardless of the genetic status of the tumours. Patients with false-negative tumours on 18F-FDOPA PET should be tested for SDHx mutations.
doi:10.1111/cen.12126
PMCID: PMC3610811  PMID: 23230826
Positron emission tomography; 18F-fluorodihydroxyphenylalanine; paraganglioma; radiopharmaceuticals; genetics
16.  Tumor Localization and Biochemical Response to Cure in Tumor-Induced Osteomalacia 
Tumor-induced osteomalacia (TIO) is a rare disorder of phosphate wasting due to fibroblast growth factor-23 (FGF23)-secreting tumors that are often difficult to locate. We present a systematic approach to tumor localization and post-operative biochemical changes in 31 subjects with TIO. All had failed either initial, or re-localization (in case of recurrence or metastases at outside institutions). Functional imaging with 111Indium-octreotide with single photon emission computed tomography (octreo-SPECT or SPECT/CT), and 18fluorodeoxyglucose positron emission tomography/CT (FDG-PET/CT) were performed, followed by anatomic imaging (CT,MRI). Selective venous sampling (VS) was performed when multiple suspicious lesions were identified or high surgical risk was a concern. Tumors were localized in 20/31 subjects (64.5%). Nineteen of 20 subjects underwent octreo-SPECT imaging, and 16/20 FDG-PET/CT imaging. Eighteen of 19 (95%) were positive on octreo-SPECT, and 14/16 (88%) on FDG-PET/CT. Twelve of 20 subjects underwent VS; 10/12 (83%) were positive. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were: sensitivity=0.95, specificity=0.64, PPV=0.82 and NPV=0.88 for octreo-SPECT; sensitivity=0.88, specificity=0.36, PPV=0.62 and NPV=0.50 for FDG-PET/CT. Fifteen subjects had their tumor resected at our institution, and were disease-free at last follow-up. Serum phosphorus returned to normal in all subjects within 1-5 days. In 10 subjects who were followed for at least 7 days postoperatively, intact FGF23 (iFGF23) decreased to near undetectable within hours and returned to the normal range within 5 days. C-terminal FGF23 (cFGF23) decreased immediately but remained elevated, yielding a markedly elevated cFGF23/iFGF23 ratio. Serum 1,25-dihydroxyvitamin D3 (1,25D) rose and exceeded the normal range. In this systematic approach to TIO tumor localization Octreo-SPECT was more sensitive and specific, but in many cases FDG-PET/CT was complementary. VS can discriminate between multiple suspicious lesions and increase certainty prior to surgery. Sustained elevations in cFGF23 and 1,25D were observed, suggesting novel regulation of FGF23 processing and 1,25D generation.
doi:10.1002/jbmr.1881
PMCID: PMC3900247  PMID: 23362135
FGF23; hypophosphatemia; mineral metabolism; vitamin D
17.  Molecular Imaging of Neuroendocrine Tumors 
Seminars in oncology  2010;37(6):662-679.
Neuroendocrine tumors (NET) are a heterogeneous group of tumors that arise from neuroendocrine cells. These tumors may arise from various organs, including lung, thymus, thyroid, stomach, duodenum, small bowel, large bowel, appendix, pancreas, adrenal, and skin. Most are well differentiated and have the ability to produce biogenic amines and various hormones. NET usually occur sporadically but they also be associated with various familial syndromes. For the vast majority of NET, surgical resection is the treatment of choice whenever feasible. Localization of NET prior to surgery and for staging and follow-up relies on both anatomic and functional imaging modalities. In fact, the unique secretory characteristics of these tumors lend themselves to imaging by molecular imaging modalities, which can target specific metabolic pathways or receptors. Neuroendocrine cells have a variety of such target receptors and pathways for which radiopharmaceuticals have been developed, including [123I/131I]-metaiodobenzylguanidine (MIBG), [ 111In]pentetreotide, [68Ga] somatostatin analogs, [18F] fluorodeoxyglucose (FDG), [11C/18F] dihydroxyphenylalanine (DOPA), [11C] 5-hydroxytryptophan (5-HTP) 99mTc pentavalent dimercaptosuccinic acid ([99mTc] (V) DMSA, and [18F] fluorodopamine (FDA). Here, we review the molecular imaging approaches for NET using various radiopharmaceuticals.
doi:10.1053/j.seminoncol.2010.10.015
PMCID: PMC4003904  PMID: 21167384
18.  Aid-Assisted Decision-Making and Colorectal Cancer Screening 
Background
Shared decision-making (SDM) is a widely recommended yet unproven strategy for increasing colorectal cancer (CRC) screening uptake. Previous trials of decision aids to increase SDM and CRC screening uptake have yielded mixed results.
Purpose
To assess the impact of decision aid–assisted SDM on CRC screening uptake.
Design
RCT.
Setting/participants
The study was conducted at an urban, academic safety-net hospital and community health center between 2005 and 2010. Participants were asymptomatic, average-risk patients aged 50–75 years due for CRC screening.
Intervention
Study participants (n=825) were randomized to one of two intervention arms (decision aid plus personalized risk assessment or decision aid alone) or control arm. The interventions took place just prior to a routine office visit with their primary care providers.
Main outcome measures
The primary outcome was completion of a CRC screening test within 12 months of the study visit. Logistic regression was used to identify predictors of test completion and mediators of the intervention effect. Analysis was completed in 2011.
Results
Patients in the decision-aid group were more likely to complete a screening test than control patients (43.1% vs 34.8%; p=0.046) within 12 months of the study visit; conversely, test uptake for the decision aid and decision aid plus personalized risk assessment arms was similar (43.1% vs 37.1%; p=0.15). Assignment to the decision-aid arm (AOR 1.48; 95% CI=1.04, 2.10), black race (AOR 1.52, 95% CI=1.12, 2.06) and a preference for a patient-dominant decisionmaking approach (AOR, 1.55; 95% CI=1.02, 2.35) were independent determinants of test completion. Activation of the screening discussion and enhanced screening intentions mediated the intervention effect.
Conclusions
Decision aid–assisted SDM has a modest impact on CRC screening uptake. A decision aid plus personalized risk assessment tool is no more effective than a decision aid alone.
doi:10.1016/j.amepre.2012.08.018
PMCID: PMC3966107  PMID: 23159252
19.  Purine-rich foods intake and recurrent gout attacks 
Annals of the rheumatic diseases  2012;71(9):1448-1453.
Objective
To examine and quantify the relation between purine intake and the risk of recurrent gout attacks among gout patients.
Methods
The authors conducted a case-crossover study to examine associations of a set of putative risk factors with recurrent gout attacks. Individuals with gout were prospectively recruited and followed online for 1 year. Participants were asked about the following information when experiencing a gout attack: the onset date of the gout attack, clinical symptoms and signs, medications (including antigout medications), and presence of potential risk factors (including daily intake of various purine-containing food items) during the 2-day period prior to the gout attack. The same exposure information was also assessed over 2-day control periods.
Results
This study included 633 participants with gout. Compared with the lowest quintile of total purine intake over a 2-day period, OR of recurrent gout attacks were 1.17, 1.38, 2.21 and 4.76, respectively, with each increasing quintile (p for trend <0.001). The corresponding OR were 1.42, 1.34, 1.77 and 2.41 for increasing quintiles of purine intake from animal sources (p for trend <0.001), and 1.12, 0.99, 1.32 and 1.39 from plant sources (p=0.04), respectively. The effect of purine intake persisted across subgroups by sex, use of alcohol, diuretics, allopurinol, NSAIDs and colchicine.
Conclusions
The study findings suggest that acute purine intake increases the risk of recurrent gout attacks by almost fivefold among gout patients. Avoiding or reducing amount of purine-rich foods intake, especially of animal origin, may help reduce the risk of gout attacks.
doi:10.1136/annrheumdis-2011-201215
PMCID: PMC3889483  PMID: 22648933
20.  Epidemiology, Treatment Patterns, and Outcomes of Metastatic Soft Tissue Sarcoma in a Community-Based Oncology Network 
Sarcoma  2014;2014:145764.
Purpose. To assess epidemiology, treatment patterns, and outcomes of metastatic soft tissue sarcoma (mSTS) patients in USA community oncology practices. Methods. This retrospective, descriptive study used US Oncology's iKnowMed electronic health records database. Adults (≥18 years) with mSTS and at least two visits between July 2007 and June 2010 were included. Key outcomes were practice patterns, overall survival (OS), and progression-free survival (PFS). Results. 363 mSTS patients (174 treated and 189 untreated) met the prespecified exclusion/inclusion criteria. The most common subtypes were leiomyosarcoma (n = 104; 29%), liposarcoma (n = 40; 11%), and synovial sarcoma (n = 12; 3%); the remainder (n = 207; 57%) comprised 27 histologic subtypes. Treated patients were younger and had lower ECOG scores; 75% and 25% received first-line combination or monotherapy, respectively. Median OS of treated and untreated patients was 22 and 17 months, respectively, and 29 months in patients with the three most common subtypes. Before controlling for effects of covariates, younger age and lower ECOG scores were associated with better OS and PFS. Conclusion. This study provides insights into mSTS epidemiology, treatment patterns, and outcomes in a large community-based oncology network. These results warrant further studies with larger cohorts.
doi:10.1155/2014/145764
PMCID: PMC3942092  PMID: 24683310
21.  Cherry Consumption and the Risk of Recurrent Gout Attacks 
Arthritis and rheumatism  2012;64(12):4004-4011.
Objective
To study the relation between cherry intake and the risk of recurrent gout attacks among individuals with gout.
Methods
We conducted a case-crossover study to examine associations of a set of putative risk factors with recurrent gout attacks. Individuals with gout were prospectively recruited and followed online for one year. Participants were asked about the following information when experiencing a gout attack: the onset date of the gout attack, symptoms and signs, medications (including anti-gout medications), and potential risk factors (including daily intake of cherries and cherry extract) during the 2-day period prior to the gout attack. We assessed the same exposure information over 2-day control periods. We estimated the risk of recurrent gout attacks related to cherry intake using conditional logistic regression.
Results
Our study included 633 individuals with gout. Cherry intake over a 2-day period was associated with a 35% lower risk of gout attacks compared with no intake (multivariate odds ratio [OR] = 0.65, 95% CI: 0.50-0.85). Cherry extract intake showed a similar inverse association (multivariate OR=0.55, 95% CI: 0.30-0.98). The effect of cherry intake persisted across subgroups by sex, obesity status, purine intake, alcohol use, diuretic use, and use of anti-gout medications. When cherry intake was combined with allopurinol use, the risk of gout attacks was 75% lower than periods without either exposure (OR=0.25, 95% CI: 0.15-0.42).
Conclusions
These findings suggest that cherry intake is associated with a lower risk of gout attacks.
doi:10.1002/art.34677
PMCID: PMC3510330  PMID: 23023818
Cherry; gout; case-crossover study
22.  Evaluating Use Characteristics for the Oncotype Dx 21-Gene Recurrence Score and Concordance With Chemotherapy Use in Early-Stage Breast Cancer 
Journal of Oncology Practice  2013;9(4):182-187.
Patients who are younger, have better ECOG performance status, or have higher grade tumors are more likely to undergo recurrence score testing.
Purpose:
Oncotype Dx 21-gene assay recurrence score (RS) predicts recurrence of early-stage breast cancer (ESBC). We investigated whether patient, tumor, or practice characteristics drive its use and explored Oncotype DX RS and chemotherapy use in subgroups.
Methods:
Patients with ESBC with documented estrogen receptor–positive, lymph node–negative, human epidermal growth factor receptor 2–negative tumors registered within McKesson Specialty Health's iKnowMed electronic health record were included. Patient and practice characteristics by region and size were analyzed. The association between Oncotype DX RS value and use of chemotherapy were assessed.
Results:
The study included 6,229 patients. Of these, 1,822 (29%) had an Oncotype DX RS result. Test use was 36%, 38%, 34%, 25%, and 6%, respectively, in patients age ≤ 45, 46-55, 56-65, 66-75, and ≥ 76 years; 33%, 25%, and 9% in patients with Eastern Cooperative Oncology Group performance status of 0, 1, and ≥ 2; 7%, 9%, 25%, 38%, 27%, and 10% in T1mic, T1a, T1b, T1c, T2, and T3 tumors; and 26%, 32%, and 33% for grades 1, 2, and 3 tumors. Of the 1,822 patients with available Oncotype DX RS, adjuvant chemotherapy use was 6%, 42%, and 84% in the low-, intermediate-, and high-risk groups.
Conclusion:
Patients who were younger, had better ECOG performance status, or had higher grade tumors were more likely to undergo RS testing. It appears that the RS test may have influenced the decision about whether to administer adjuvant chemotherapy: a low RS score was associated with lower chemotherapy use and a high RS score was associated with higher chemotherapy use.
doi:10.1200/JOP.2012.000638
PMCID: PMC3710166  PMID: 23942918
23.  BOSTON PATIENT NAVIGATION RESEARCH PROGRAM: The Impact of Navigation on Time to Diagnostic Resolution after Abnormal Cancer Screening 
Background
There is a need for controlled studies to assess the impact of patient navigation in vulnerable cancer populations.
Methods
Boston Patient Navigation Research Program conducted a quasi-experimental patient navigation intervention across six federally qualified inner-city community health centers, three assigned to a breast cancer navigation intervention and three assigned to a cervical cancer navigation intervention; each group then served as the control for the other. Eligible women had an abnormal breast or cervical cancer screening test performed at one of the participating health centers during a baseline (2004–2005) or intervention period (2007–2008). Kaplan-Meier survival curves and proportional hazards regression examined the effect of patient navigation on time to definitive diagnosis, adjusting for covariates, clustering by clinic and differences between the baseline and intervention period.
Results
We enrolled 997 subjects in the baseline period and 3,041 subjects during the intervention period, of whom 1,497 were in the navigated arm, and 1,544 in the control arm. There was a significant decrease in time to diagnosis for subjects in the navigated group compared with controls among those with a cervical screening abnormality (aHR 1.46, 95% CI: 1.1–1.9); and among those with a breast cancer screening abnormality who resolved after 60 days (aHR 1.40, 95% CI: 1.1–1.9), with no differences before 60 days.
Conclusions
This study documents a benefit of patient navigation on time to diagnosis among a racially/ethnically diverse inner city population.
Impact
Patient navigation may address cancer health disparities by reducing time to diagnosis following an abnormal cancer screening event.
doi:10.1158/1055-9965.EPI-12-0532
PMCID: PMC3472624  PMID: 23045539
24.  Methadone Dose, Take Home Status and Hospital Admission among Methadone Maintenance Patients 
Journal of addiction medicine  2012;6(3):186-190.
Objectives
Among patients receiving methadone maintenance treatment (MMT) for opioid dependence, receipt of unobserved dosing privileges (take homes) and adequate doses (i.e. ≥ 80mg) are each associated with improved addiction treatment outcomes, but the association with acute care hospitalization is unknown. We studied whether take-home dosing and adequate doses (i.e. ≥ 80 mg) were associated with decreased hospital admission among patients in a MMT program.
Methods
We reviewed daily electronic medical records of patients enrolled in one MMT program to determine receipt of take home doses, methadone dose ≥ 80mg and hospital admission date. Non-linear mixed effects logistic regression models were used to evaluate whether take home doses or dose ≥ 80mg on a given day were associated with hospital admission on the subsequent day. Covariates in adjusted models included age, gender, race/ethnicity, HIV status, medical illness, mental illness, and polysubstance use at program admission.
Results
Subjects (n=138) had the following characteristics: mean age 43 years; 52% female; 17% HIV-infected; 32% medical illness; 40% mental illness; and 52% polysubstance use. During a mean follow-up of 20 months, 42 patients (30%) accounted for 80 hospitalizations. Receipt of take homes was associated with significantly lower odds of a hospital admission (AOR 0.26; 95%CI: 0.11-0.62), whereas methadone dose ≥ 80mg was not (AOR 1.01; 95% CI: 0.56-1.83).
Conclusions
Among MMT patients, receipt of take homes, but not dose of methadone, was associated with decreased hospital admission. Take home status may reflect not only patients’ improved addiction outcomes, but also reduced healthcare utilization.
doi:10.1097/ADM.0b013e3182584772
PMCID: PMC3416958  PMID: 22694929
Methadone maintenance treatment; dose; take home status; hospital admission
25.  The Your Disease Risk Index for Colorectal Cancer Is an Inaccurate Risk Stratification Tool for Advanced Colorectal Neoplasia at Screening Colonoscopy 
Tailoring the use of screening colonoscopy based on the risk of advanced colorectal neoplasia (ACN) could optimize the cost-effectiveness of colorectal cancer (CRC) screening. Our goal was to assess the accuracy of the Your Disease Risk (YDR) CRC risk index for stratifying average risk patients into low- versus intermediate/high-risk categories for ACN. The YDR risk assessment tool was administered to 3,317 asymptomatic average risk patients 50 to 79 years of age just before their screening colonoscopy. Associations between YDR-derived relative risk (RR) scores and ACN prevalence were examined using logistic regression and χ2 analyses. ACN was defined as a tubular adenoma ≥1 cm, tubulovillous or villous adenoma of any size, and the presence of high-grade dysplasia or cancer. The overall prevalence of ACN was 5.6%. Although YDR-derived RR scores were linearly associated with ACN after adjusting for age and gender (P = 0.033), the index was unable to discriminate "below average" from "above/average" risk patients [OR, 1.01; 95% confidence interval (CI), 0.75–1.37]. Considerable overlap in rates of ACN was also observed between the different YDR risk categories in our age- and gender-stratified analyses. The YDR index lacks accuracy for stratifying average risk patients into low- versus intermediate/high-risk categories for ACN.
doi:10.1158/1940-6207.CAPR-12-0014
PMCID: PMC3632311  PMID: 22689913

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