Jonathan Assayag

The use of pioglitazone and the risk of bladder cancer in people with type 2 diabetes: nested case-control study

Objective To determine if the use of pioglitazone is associated with an increased risk of incident bladder cancer in people with type 2 diabetes. Design Retrospective cohort study using a nested case-control analysis. Setting Over 600 general practices in the United Kingdom contributing to the general practice research database. Participants The cohort consisted of people with type 2 diabetes who were newly treated with oral hypoglycaemic agents between 1 January 1988 and 31 December 2009. All incident cases of bladder cancer occurring during follow-up were identified and matched to up to 20 controls on year of birth, year of cohort entry, sex, and duration of follow-up. Exposure was defined as ever use of pioglitazone, along with measures of duration and cumulative dosage. Main outcome measure Risk of incident bladder cancer associated with use of pioglitazone. Results The cohort included 115 727 new users of oral hypoglycaemic agents, with 470 patients diagnosed as having bladder cancer during follow-up (rate 89.4 per 100 000 person years). The 376 cases of bladder cancer that were diagnosed beyond one year of follow-up were matched to 6699 controls. Overall, ever use of pioglitazone was associated with an increased rate of bladder cancer (rate ratio 1.83, 95% confidence interval 1.10 to 3.05). The rate increased as a function of duration of use, with the highest rate observed in patients exposed for more than 24 months (1.99, 1.14 to 3.45) and in those with a cumulative dosage greater than 28 000 mg (2.54, 1.05 to 6.14). Conclusion The use of pioglitazone is associated with an increased risk of incident bladder cancer among people with type 2 diabetes.

Correlating metabolic activity on 18F-FDG PET/CT with histopathologic characteristics of osseous and soft-tissue sarcomas: a retrospective review of 136 patients.

OBJECTIVE The objective of our study was to determine whether there is a statistically significant correlation between metabolic activity of osseous and soft-tissue sarcomas as measured by the maximum standardized uptake value (SUV(max)) on (18)F-FDG PET/CT and histopathologic characteristics such as mitotic counts, the presence of necrosis, and the presence of a myxoid component. MATERIALS AND METHODS We retrospectively evaluated 238 consecutive patients with known soft-tissue or osseous sarcoma who underwent (18)F-FDG PET/CT for initial staging or assessment for recurrence of disease. The SUV(max) of each primary or of the most intense metastatic lesion was measured and was compared with the histologic data provided in the final pathology reports. RESULTS Histopathologic data were available for 136 sarcomas. The median SUV(max) values of sarcomas with mitotic counts of less than 2.00 (per 10 high-power fields [HPF]), 2.00-6.99, 7.00-16.24, and 16.25 or greater were 5.0, 6.6, 10.3, and 13.0, respectively (p = 0.0003). The median SUV(max) for the sarcomas with necrosis (90 patients) was 8.6 and for those without necrosis (43 patients), 6.0 (p = 0.026). The median SUV(max) for the sarcomas without a myxoid component (118 patients) was 7.7 and with a myxoid component (16 patients) was 6.2 (p = 0.28). CONCLUSION There was a statistically significant correlation between the mitotic count and the SUV(max) as well as between the presence of tumor necrosis and the SUV(max). Although a correlation between the presence of a myxoid component and SUV(max) was shown, it was not found to be statistically significant. These findings improve on the current information in the literature regarding the use of PET/CT for guidance in sarcoma biopsy. Correlating the SUV(max) with histologic markers that also feature prominently in major sarcoma grading systems may help improve the accuracy of grading and of prognostication by allowing the SUV(max) to potentially serve as a surrogate marker in these grading systems, particularly in cases in which there is interobserver disagreement in the pathologic diagnosis or in cases in which the sarcoma cannot be properly classified on the basis of histopathologic evaluation alone.

Altered Hepatic Metabolic Activity in Patients With Hepatic Steatosis on FDG PET/CT

OBJECTIVE FDG PET studies frequently use the liver as an internal reference organ to assess the significance of FDG uptake in pathologic processes involving other organs. The purpose of this study was to assess whether hepatic steatosis has a significant effect on the standardized uptake value (SUV) of the liver. SUBJECTS AND METHODS This prospective case-control study analyzed FDG PET/CT scans of patients with frank hepatic steatosis on the unenhanced CT portion of the study. Maximum SUVs (corrected for both body weight [SUV(bw)] and lean body mass [SUV(lbm)]) in 37 patients with hepatic steatosis were compared with those in 37 control patients without hepatic steatosis. RESULTS Patients with hepatic steatosis had statistically significant smaller mean (± SD) values than did the control subjects for liver SUV(lbm) (1.91 ± 0.57 vs 2.17 ± 0.36), liver SUV(lbm)-mediastinum ratio (1.23 ± 0.19 vs 1.35 ± 0.19), and liver SUV(bw)-mediastinum ratio (1.24 ± 0.16 vs 1.39 ± 0.22). CONCLUSION Hepatic steatosis results in a small statistically significant decrease in hepatic metabolic activity, as measured by FDG PET. However, because the degree of change is small, compared with healthy control subjects, this decrease is unlikely to have any clinical significance on the use of the liver as an internal reference organ.

The Use of Aspirin and the Risk of Mortality in Patients with Prostate Cancer

PURPOSE The association between the use of aspirin and mortality in patients with prostate cancer remains uncertain. We determine whether the use of aspirin in patients with prostate cancer is associated with a decreased risk of prostate cancer mortality and all cause mortality. MATERIALS AND METHODS Using the United Kingdom National Cancer Data Repository, Clinical Practice Research Datalink and associated databases, we identified a cohort of men with nonmetastatic prostate cancer between 1998 and 2009, followed until 2012. Cox proportional hazards models were used to estimate adjusted HRs with 95% CIs of mortality outcomes associated with post-diagnostic use of aspirin defined as a time-varying exposure. Effect modification by pre-diagnostic aspirin use was also assessed. RESULTS The cohort included 11,779 men followed for 5.4 years (SD 2.9). Post-diagnostic aspirin use was associated with an increased risk of prostate cancer mortality (HR 1.46, 95% CI 1.29-1.65) and all cause mortality (HR 1.37, 95% CI 1.26-1.50). These increased risks were restricted to patients initiating aspirin after the prostate cancer diagnosis (HR 1.84, 95% CI 1.59-2.12, and HR 1.70, 95% CI 1.53-1.88, respectively), and not in patients who were already exposed to aspirin before the diagnosis (HR 0.97, 95% CI 0.81-1.16 and HR 0.98, 95% CI 0.87-1.18, respectively). CONCLUSIONS The post-diagnostic use of aspirin is not associated with a decreased risk of prostate cancer outcomes. Increased risks were restricted to patients initiating these drugs after their diagnosis, suggesting a noncausal association.

Post-diagnostic use of beta-blockers and the risk of death in patients with prostate cancer.

BACKGROUND Recent observational studies have produced conflicting results with respect to beta-blocker use after prostate cancer diagnosis and mortality outcomes. OBJECTIVE To determine whether post-diagnostic use of beta-blockers is associated with prostate cancer mortality and all-cause mortality. PATIENTS AND METHODS A cohort of 6270 men newly-diagnosed with non-metastatic prostate cancer between 1st April 1998, and 31st December 2009, followed until 1st October 2012, was identified using large population-based electronic databases from the United Kingdom. Time-dependent Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of mortality outcomes associated with post-diagnostic use of beta-blockers. Secondary analyses were performed to examine the independent effects of non-selective beta-blockers, as well as cumulative duration of use. RESULTS During a mean follow-up time of 3.8 years (standard deviation: 2.7 years), 1761 deaths occurred, including 715 from prostate cancer. Post-diagnostic use of beta-blockers was not associated with a decreased risk of prostate cancer mortality (HR: 0.97, 95% CI: 0.72-1.31) and all-cause mortality (HR: 0.97, 95% CI: 0.81-1.16). There was no statistically significant association for non-selective beta-blockers (prostate cancer mortality, HR: 1.05, 95% CI: 0.72-1.53 and all-cause mortality, HR: 0.94, 95% CI: 0.74-1.18), and no statistically significant trends of cumulative duration of use for both mortality outcomes. CONCLUSION The use of beta blockers, including those of the non-selective type, was not associated with a decreased risk of prostate cancer and all-cause mortality.

Resumption of Warfarin Therapy After Gastrointestinal Tract Bleeding: Benefit or Bias?

formation than conventional “typical” vs “atypical” distinctions. Our study is internally valid because symptoms were validated against the gold standard, coronary angiography. Our modest sample size is sufficiently powered; in addition, our study represents “real-world” practice and is one of the few prospective studies of cardiac symptoms to date. In conclusion, the symptom continuum according to sex and gender has empirically demonstrated the substantial overlap of shared symptoms between men and women with obstructive CAD. This information can help clinicians to better contextualize symptoms associated with obstructive CAD rather than adhering to the conventional “typical” and “atypical” angina distinction. Future studies should seek to test and validate the symptom continuum according to gender in diverse patient populations.