The application of cytogenetics and fluorescence in situ hybridization to fine‐needle aspiration in the diagnosis and subclassification of renal neoplasms

BACKGROUND:

Percutaneous fine‐needle aspiration (FNA) cytology is an important diagnostic test for the evaluation and management of selected renal masses. Cytogenetic analysis of cytology specimens can serve as an adjunct for precise classification because certain tumors are associated with specific chromosomal aberrations. This study summarizes our experience with the application of conventional cytogenetics and fluorescence in situ hybridization (FISH) to renal FNA specimens.

METHODS:

All percutaneous renal FNAs performed during 2005 through 2008 were identified from the electronic pathology database. Results of cytogenetic and FISH analyses were correlated with the final diagnoses of the renal FNAs.

RESULTS:

A total of 303 renal FNAs were performed. During an onsite assessment, a portion of the cytology specimen was allocated for cytogenetic analysis in 74 cases. Karyotypic analysis or FISH was successful in 44 (59%) of these. Characteristic chromosomal abnormalities were observed in 27 cases. In 17 cases, a karyotype revealed a combination of trisomies/tetrasomies and in another 5 cases, FISH revealed trisomy 7 and 17, both of which are consistent with papillary renal cell carcinoma (RCC). Two cases showed 3p deletions consistent with clear cell RCC. Trisomy 3 was observed in 1 case of clear cell RCC. Monosomy 1 and 17 was observed in a case of papillary RCC comprised oncocytic cells. In 1 case of primary renal synovial sarcoma, FISH revealed a rearrangement at the SYT locus (18q11.2).

CONCLUSIONS:

Renal FNA specimens are amenable to analysis by cytogenetics and FISH in the diagnosis and subclassification of renal neoplasms. Cancer (Cancer Cytopathol) 2010. © 2010 American Cancer Society.     

Incidence and epidemiology of non‐Hodgkin lymphoma and risk of second malignancy among 22 466 survivors in Israel with 30 years of follow‐up

Previous studies have shown an increase risk of second malignancies after non‐Hodgkin's lymphoma (NHL), which is probably related to a combination of factors including genetic predisposition, molecular background, host immunological status and therapy administered. Here, we determined the incidence of NHL and risk of second solid tumours and haematological malignancies among survivors of NHL diagnosed in Israel during 1980–2011. Data were collected from the records of the Israeli National Cancer Registry. The total cohort of 24 666 NHL‐patients included 22 601 Jews and 2065 Arabs. Median age of diagnosis for Jews was 61.3 years and 48.2 for Arab patients. Of the Jews with NHL, 11 265 (50%) were of European–American origin, 5005 (22%) Asian or African and 6114 (27%) were born in Israel. Second cancers were recorded in 2010 NHL survivors, 1918 Jews and 92 Arabs, representing a rate of 8.5%, and 4.5% o, respectively. Second malignancies in all recorded sites were more frequent than in the general population, with a standardized incidence ratio (SIR) of 1.28 for Jewish men, 1.25 for Jewish women, 1.73 for Arab men and 1.98 for Arab women. This higher risk was even more pronounced for the 309 cases with secondary haematological malignancies (secondary haematological malignancies of 1.97, 1.81, 4.48 and 4.15, respectively). Our findings show that there is an increased risk of second malignancies occurring after diagnosis of NHL in Israel, particularly for haematological malignancies such as leukaemia and NHL. The differences we report in the incidence of NHL and the types of second malignancies occurring among Jews and Arabs suggest that ethnicity and genetic susceptibility may be important relevant risk factors. Copyright © 2016 John Wiley & Sons, Ltd.     

Smoky coal,tobacco smoking,and lung cancer risk in Xuanwei,China

Objectives

Lung cancer rates in Xuanwei are the highest in China. In-home use of smoky coal has been associated with lung cancer risk, and the association of smoking and lung cancer risk strengthened after stove improvement. Here, we explored the differential association of tobacco use and lung cancer risk by the intensity, duration, and type of coal used.

Materials and methods

We conducted a population-based case-control study of 260 male lung cancer cases and 260 age-matched male controls. Odds ratios (OR) and 95% confidence interval (CI) for tobacco use was calculated by conditional logistic regression.

Results

Use of smoky coal was significantly associated with an increased risk of lung cancer, and tobacco use was weakly and non-significantly associated with lung cancer risk. When the association was assessed by coal use, the cigarette-lung cancer risk association was null in hazardous coal users and elevated in less hazardous smoky coal users and non-smoky coal users. The risk of lung cancer per cigarette per day decreased as annual use of coal increased (>0–3 tons: OR: 1.09; 95% CI: 1.03–1.17; >3 tons: OR: 0.99; 95% CI: 0.95–1.03). Among more hazardous coal users, attenuation occured at even low levels of usage (>0–3 tons: OR: 1.02; 95% CI: 0.91–1.14; >3 tons: OR: 0.94; 95% CI: 0.97–1.03).

Conclusion

We found evidence that smoky coal attenuated the tobacco and lung cancer risk association in males that lived in Xuanwei, particularly among users of hazardous coal where even low levels of smoky coal attenuated the association. Our results suggest that the adverse effects of tobacco may become more apparent as China's population continues to switch to cleaner fuels for the home, underscoring the urgent need for smoking cessation in China and elsewhere.     

Building community capacity in public health: the role of action-oriented partnerships.

Public health practice increasingly is concerned with the capacity and performance of communities to identify, implement, strengthen, and sustain collective efforts to improve health. The authors developed ways to assist local Turning Point partnerships to improve their community public health system as a secondary outcome of their work on the expressed needs of the community. Using focus groups, meeting minutes, attendance records, and meeting observation, the authors fed information back to the partnerships on systems change. A public health systems improvement plan supportive of local partnerships' work on specific health issues was funded and the collaborative research agenda was further refined.     

A meta-analysis of bladder cancer and diesel exhaust exposure

The aim of this study is to review and summarize the available epidemiologic studies of bladder cancer and occupational exposure to diesel exhaust. We retrieved relevant studies and abstracted their characteristics and results. We assessed the heterogeneity of the results to decide whether to perform a fixed-effects model meta-analysis. We identified 35 relevant studies. No overall meta-analysis was performed because of heterogeneity in results. Results of railroad workers (N = 14) suggested an increased occurrence of bladder cancer, but we did not conduct a meta-analysis. The summary relative risk (RR) among truck drivers was 1.17 (95% confidence interval [CI] = 1.06-1.29, 15 studies) and that among bus drivers was 1.33 (95% CI = 1.22-1.45, 10 studies). Ten studies considered diesel exhaust exposure based on a job exposure matrix or a similar approach; the summary RR for these studies was 1.13 (95% CI = 1.00-1.27). A positive dose-response relation was suggested by 10 of the 12 studies that provided relevant information. The summary RR for high diesel exposure was 1.44 (95% CI = 1.18-1.76). There was some evidence of publication bias, however, with a lack of small studies with null or negative results. Our review suggests that exposure to diesel exhaust may increase the occurrence of bladder cancer, but the effects of misclassification, publication bias, and confounding cannot be fully taken into account.     

Smoking status,usual adult occupation,and risk of recurrent urothelial bladder carcinoma: data from The Cancer Genome Atlas (TCGA) Project

Purpose

Tobacco smoking and occupational exposures are the leading risk factors for developing urothelial bladder carcinoma (UBC), yet little is known about the contribution of these two factors to risk of UBC recurrence. We evaluated whether smoking status and usual adult occupation are associated with time to UBC recurrence for 406 patients with muscle-invasive bladder cancer submitted to The Cancer Genome Atlas (TCGA) project.

Methods

Kaplan–Meier and Cox proportional hazard methods were used to assess the association between smoking status, employment in a high-risk occupation for bladder cancer, occupational diesel exhaust exposure, and 2010 Standard Occupational Classification group and time to UBC recurrence.

Results

Data on time to recurrence were available for 358 patients over a median follow-up time of 15 months. Of these, 133 (37.2%) experienced a recurrence. Current smokers who smoked for more than 40 pack-years had an increased risk of recurrence compared to never smokers (HR 2.1, 95% CI 1.1, 4.1). Additionally, employment in a high-risk occupation was associated with a shorter time to recurrence (log-rank p = 0.005). We found an increased risk of recurrence for those employed in occupations with probable diesel exhaust exposure (HR 1.8, 95% CI 1.1, 3.0) and for those employed in production occupations (HR 2.0, 95% CI 1.1, 3.6).

Conclusions

These findings suggest smoking status impacts risk of UBC recurrence, although several previous studies provided equivocal evidence regarding this association. In addition to the known causal relationship between occupational exposure and bladder cancer risk, our study suggests that occupation may also be related to increased risk of recurrence.

     

Symmetric double-headed aminopyridines, a novel strategy for potent and membrane-permeable inhibitors of neuronal nitric oxide synthase

We report novel neuronal nitric oxide synthase (nNOS) inhibitors based on a symmetric double-headed aminopyridine scaffold. The inhibitors were designed from crystal structures of leads 1 and 2 (Delker, S. L.; Ji, H.; Li, H.; Jamal, J.; Fang, J.; Xue, F.; Silverman, R. B.; Poulos, T. L. Unexpected binding modes of nitric oxide synthase inhibitors effective in the prevention of cerebral palsy . J. Am. Chem. Soc. 2010, 132, 5437-5442) and synthesized using a highly efficient route. The best inhibitor, 3j, showed low nanomolar inhibitory potency and modest isoform selectivity. It also exhibited enhanced membrane permeability. Inhibitor 3j binds to both the substrate site and the pterin site in nNOS but only to the substrate site in eNOS. These compounds provide a basis for further development of novel, potent, isoform selective, and bioavailable inhibitors for nNOS.     

Effects of urine testing frequency on outcome in a methadone take-home contingency program

We examined the effects of urine testing frequency on treatment outcome in a contingent methadone take-home program. Study patients who submitted<80% opiate and/or cocaine positive urines during a 5-week baseline received 60 mg methadone throughout the study, submitted urine samples on Monday, Wednesday, and Friday, and were randomized into one of three take-home incentive conditions. Study patients could receive three take-home doses per week if one urine sample randomly selected each week (Weekly; n=16) or each month (Monthly; n=18) was negative for opiates and cocaine. Take-homes for Random Drawing control patients (n=19) were determined weekly independent of urine test results. Subjects in the Weekly group showed an immediate increase from baseline in percentage of drug-free urines; those in the Monthly group showed a gradual increase over the first 3 months; and those in Random Drawings showed a decline in percentage of drug-free urines over time. The percentage of patients with sustained (8 or more weeks) opiate and cocaine abstinence was 56.6, 38.9 and 10.5% for Weekly, Monthly and Random Drawing groups, respectively (P<0.002). These results confirm that methadone take-homes contingent on drug-free urines prevent a decline in treatment performance over time and suggest that abstinence can be sustained with urine testing conducted as infrequently as once a month.     

The effectiveness of incentives in enhancing treatment attendance and drug abstinence in methadone-maintained pregnant women

This study examined the effectiveness of short-term contingency management for eliminating cocaine use and increasing full day treatment attendance with pregnant methadone-maintained women randomly assigned to either an escalating voucher incentive schedule (n=44) or non-incentive (n=36) conditions. Full day treatment attendance and urine toxicology for cocaine and heroin were assessed and consequated for 14 days. The escalating voucher incentive schedule significantly increased full day treatment attendance and drug abstinence compared to the non-incentive schedule. These results suggest that reinforcing the co-occurrence of two required behaviors (treatment attendance and abstinence from illicit drug use) is effective, and may be an important adjunct to methadone pharmacotherapy for treating pregnant drug dependent women.