High spectral and spatial resolution MRI of age‐related changes in murine prostate

The purpose of this work was to evaluate high‐resolution echo‐planar spectroscopic MRI of normal and precancerous prostatic changes in a transgenic mouse line. Simian virus large T‐antigen transgenic male mice (N = 7, age = 34 ± 3.7 weeks) with prostatic hyperplasia and intraepithelial neoplasia (PIN) were studied. High spectral and spatial resolution (HiSS) MRI of the water proton signal was compared to the free induction decay (FID) integral image and conventional gradient‐echo and spin‐echo imaging. Water peak‐height images of the prostate produced from HiSS datasets showed improved contrast‐to‐noise ratio (CNR) (P < 0.03), and greater morphological detail (P < 0.004) based on texture analysis. Despite the high spectral resolution of the HiSS datasets, signal‐to‐noise ratio (SNR) compared favorably with that of the FID integral and conventional images. Lobular features in HiSS images of older mice were consistent with hyperplasia seen on histology. A partially deuterated water‐filled catheter was inserted in the mouse rectum for susceptibility matching between the colon interior and exterior to minimize image artifacts. These preliminary results suggest that HiSS MRI provides detailed morphology of the murine prostate and can detect early changes associated with the development of cancer. HiSS MRI of patients may have similar advantages. Magn Reson Med 60:575–581, 2008. © 2008 Wiley‐Liss, Inc.     

Trastuzumab mediated cardiotoxicity in the setting of adjuvant chemotherapy for breast cancer: a retrospective study

Background The incidence and management of trastuzumab-mediated cardiotoxicity outside of clinical trials has not been well described. Objective and methods The aim of the study was to retrospectively evaluate the incidence of cardiac dysfunction, characterize its natural history, and identify the degree of reversibility using cardiac MRI, in a population of HER-2 positive breast cancer patients receiving trastuzumab in the adjuvant setting. Results Out of 152 patients (mean age 52 ± 10 years), 36 (24%) developed trastuzumab mediated cardiomyopathy, the majority asymptomatic. Factors that predicted the development of trastuzumab mediated cardiac dysfunction were a pre-existing history of hypertension, smoking history, and a family history of coronary artery disease. Within 3 months of treatment with trastuzumab, there was a difference in LVEF between the normal cohort and those patients who developed LV systolic dysfunction (61 ± 5% vs. 51 ± 8%, P < 0.01). During the 6-month-followup, 34/36 patients demonstrated subepicardial linear delayed enhancement of the lateral wall of the left ventricle on cardiac MRI, suggesting trastuzumab induced myocarditis. Conclusion Approximately 1 in 4 women may develop LV systolic dysfunction after treatment with adjuvant trastuzumab, necessitating careful patient selection and close serial monitoring using noninvasive cardiac imaging.     

Fine needle aspiration of renal cortical lesions in adults

The role of fine needle aspiration (FNA) biopsy of renal cortical lesions was controversial in the past because the result of the FNA did not affect clinical management. All renal cortical lesions, except metastasis, were subject to surgical resection. However, with the advances in neoadjuvant targeted therapies, knowledge of the renal cortical tumor histological subtype is critical for tailoring clinical trials and follow‐up strategies. At present, there are clinical trials involving the use of novel kinase inhibitors for conventional (clear cell) and papillary renal cell carcinoma. We studied 143 consecutive cases of renal cortical lesions, evaluated after radical or partial nephrectomies over a 2‐year period. An air‐dried smear and a Thinprep® slide were prepared in all cases. The slides were Diff‐Quick and Papanicolaou stained, respectively. The cytology specimens were reviewed and the results were then compared with the histologic diagnosis. Cytology was highly accurate to diagnose conventional RCC, while the accuracy for papillary RCC, chromophobe RCC, and papillary urothelial carcinoma was much lower. Our results indicate that ancillary studies might have an important role in the subclassification of renal cortical neoplasms for targeted treatment. Diagn. Cytopathol. 2010;38:710–715. © 2009 Wiley‐Liss, Inc.     

Stress Echocardiography: Abnormal Tissue Doppler Imaging in the Absence of Cardiac Allograft Vasculopathy in Heart Transplant Recipients

Background: The most significant predictor of long‐term survival in heart transplant patients is the development of accelerated cardiac allograft vasculopathy (CAV). Several studies have demonstrated the usefulness of dobutamine stress echocardiography (DSE) for screening CAV, by detecting regional wall motion abnormalities. Tissue Doppler imaging (TDI)‐derived indices during DSE allow for the early detection of ischemic heart disease (IHD), prior to a reduction in regional or global systolic function. These indices include a reduction in annular systolic velocity (S′), a decrease in early diastolic annular velocity (E′), and prolongation of time to E′. In cardiac transplant patients, the application of these TDI abnormalities during DSE remains unknown. Objective: The objective of this study was to evaluate the pattern of (TDI‐derived indices of systolic and diastolic function during DSE in cardiac transplant patients without evidence of CAV. Methods: A retrospective evaluation of 30 patients (mean age 54 ± 11 years) who had both DSE and coronary angiography was performed. The control group consisted of 15 patients referred to rule out coronary artery disease while the study group consisted of 15 cardiac transplant patients referred for routine annual follow‐up. During each stage of DSE, tissue Doppler measurements of systolic (S′), early (E′), and late (A′) diastolic velocities of the lateral annulus were taken. Results: All 30 patients had normal DSE based on systolic regional function and normal coronary angiograms with no stenosis >50%. There was no difference in hemodynamic parameters during the DSE at baseline and with stress. Despite normal coronaries, cardiac transplant patients demonstrated lower S′, E′, and A′ velocities at peak stress compared to the control patients. Conclusion: Dobutamine‐induced augmentation of TDI velocities of the lateral annulus, normally observed in the absence of ischemia in nontransplanted adults, is reduced in cardiac transplant recipients.     

Intraoperative frozen section assessment of pelvic lymph nodes during radical prostatectomy is of limited value

Study Type – Therapy (case series)
Level of Evidence 4

OBJECTIVE

To evaluate the accuracy of frozen section (FS) assessment of pelvic lymph nodes (PLNs) during radical prostatectomy (RP) in a large contemporary cohort; and to analyse the contribution of FS to surgical decision making in this setting.

PATIENTS AND METHODS

During a 4‐year period at a single institution, RPs with PLN dissection (PLND) were reviewed. The number and size of the PLNs, and the size of metastases were measured.

RESULTS

FS was performed on 349 bilateral PLNDs. Overall, 28 (8%) cases were positive for metastasis, 11 of which were detected by FS (39%). The 17 false negatives, all of which contained metastases smaller than 5 mm, were due to failure to identify and freeze the positive PLNs (11), failure to section at the level of the metastatic tumour (four), or interpretative error (two). The sensitivity was not affected by the number of sampled nodes. The size of metastasis was the determining factor for the accuracy of FS, with metastases of ≥5 mm having a sensitivity of 100%, and metastases of <5 mm having a sensitivity of 10%. Among the 11 true positives, RP was aborted in eight cases and continued in three. During the same period, 261 PLNDs were performed without FS, and 18 (6.9%) had metastases.

CONCLUSIONS

FS is highly accurate in detecting large, grossly evident metastases, but performs poorly on micrometastases. It is recommended that a two‐step approach applied to routine FS starting with a careful gross examination followed by FS for only grossly suspicious PLNs.     

Hypoxia‐inducible factor and mammalian target of rapamycin pathway markers in urothelial carcinoma of the bladder: possible therapeutic implications

What’s known on the subject? and What does the study add? The hypoxia‐inducible factor (HIF) and mammalian target of rapamycin (mTOR) pathways are important in tumorigenesis and novel agents targeting these respective pathways have shown promising activity in several malignancies. The current study demonstrates the expression of HIF and mTOR related pathway markers in urothelial carcinoma providing a rationale for clinical trials evaluating agents targeting these pathways.

OBJECTIVE

To investigate the rationale for using targeted therapies against hypoxia‐inducible factor (HIF) and mammalian target of rapamycin (mTOR) pathways in urothelial carcinoma of the bladder, by studying the immunohistochemical expression of molecules of these pathways in urothelial carcinoma, as recent pre‐clinical studies and clinical trials have shown the potential utility of such targeted therapies.

PATIENTS AND METHODS

Immunohistochemical stains were performed on a tissue microarray prepared from 92 cases of ≥ pT2 urothelial (transitional cell) carcinoma of bladder, using antibodies against HIF‐1α and VEGF‐R2, and phospho‐S6 and phospho‐4E BP1, molecules of HIF and activated mTOR pathways, respectively. Immunoreactivity was graded from 0 to 3+ (0, 0–5%; 1+, 6–25%; 2+, 26–50%; 3+, > 50% tumour cells positive).

RESULTS

In all, 58, 34, 35 and 17% of the tumours showed grade 2–3+ expression of phospho‐4E BP1, phospho‐S6, HIF‐1α and VEGF‐R2, respectively. Moderate correlation for immunoreactivity was observed between molecules within the same pathway [(phospho‐4E BP1 with phospho‐S6 (rho = 0.411), and HIF‐1α with VEGF‐R2 (rho = 0.265)], but not between molecules across pathways.

CONCLUSIONS

Urothelial carcinomas of the bladder express molecules of the HIF and mTOR pathways, providing a rationale for clinical trials evaluating agents targeting these pathways. Correlation between molecules within the same pathway, and not across pathways, suggests that investigating the usefulness of a specific targeted agent might benefit from pre‐treatment evaluation of pathway marker expression.