Relationship Between the Pathologic Subtype/Initial Stage and Microliths in Testicular Germ Cell Tumors.

OBJECTIVES: To investigate the relationship between microliths and germ cell tumor histologic subtypes and determine whether microliths correlate with tumor stage at diagnosis. METHODS: A total of 1249 patients with testicular cancer seen between 1999 and 2013 were evaluated; 346 of 1249 patients (28%) with primary testicular tumors and sonographic imaging of unaffected testicular tissue formed the analytic cohort. Age, ethnicity, tumor histologic subtype, and stage at diagnosis were extracted from the medical record. Two examiners concurrently recorded the highest number of microliths per image of unaffected testicular tissue. RESULTS: A total of 175 of 346 patients (51%) had 1 or more microliths; 69 of 346 (20%) had more than 5 microliths per image. The histologic percentage of seminomas positively correlated with the microlith count (rs = 0.12; P = .036); the histologic percentage of embryonal components negatively correlated with the microlith count (rs = -0.15; P = .007). A higher microlith count was associated with a lower stage at diagnosis (P = .0243). Subgroup analysis of pure seminomas suggested a trend toward a higher microlith count in patients with lower-stage disease at diagnosis (P= .07). No association was found between the tumor stage at diagnosis and microlith count in patients with greater than 50% embryonal components of tumors (P= .55). No association was found between microliths and age, tumor size, and presence of lymphovascular/rete testis invasion (P = .120, .500, .629, and .155, respectively). CONCLUSIONS: Patients with testicular cancer who have microliths may be more likely to have a higher percentage of seminomas and a lower percentage of embryonal components in their primary tumors. Microliths also showed an association with earlier stages of disease at diagnosis.

A phase I trial of high dose gefitinib for patients with leptomeningeal metastases from non-small cell lung cancer.

INTRODUCTION: There are few effective treatment options for leptomeningeal metastasis (LM) in non-small-cell lung cancer (NSCLC). This study assessed the feasibility of high-dose gefitinib in patients with LM from NSCLC harboring EGFR mutations or prior systemic response to EGFR-TKI. METHODS: This phase I open-label trial of a novel gefitinib dosing schedule employed a 3+3 design. Eligible NSCLC patients with LM had known EGFR mutations and/or prior response to EGFR-TKI. Patients alternated 2 weeks of high-dose daily gefitinib (dose levels: 750 mg, 1000 mg, 1250 mg) with 2 weeks of maintenance therapy (500 mg daily). Primary endpoints were safety and toxicity. Secondary endpoints included overall survival (OS), neurological progression-free survival, radiological response, and cytological response in cerebrospinal fluid (CSF). RESULTS: Seven patients were treated: 3 at 750 mg dose level, 4 at 1000 mg dose level. There were no DLTs at the 750 mg dose level, and one DLT (toxic epidermal necrolysis) at the 1000 mg dose level. The study was closed due to slow accrual. Median neurological PFS was 2.3 months (range 1.6-4.0 months); median OS was 3.5 months (range 1.6-5.1 months). Though there were no radiologically documented remissions of LM disease, four patients had improvement in neurological symptoms. One patient cleared their CSF of NSCLC cells, while 2 others had decrease in malignant cells in CSF. CONCLUSION: Although the MTD was not defined due to slow accrual, this study provides important information about the tolerability and CSF penetration of high-dose gefitinib as a therapeutic option for modest palliation for NSCLC patients with LM and a known EGFR mutation.

The management of retroperitoneal lymphadenopathy in spermatocytic seminoma of the testicle.

Spermatocytic seminoma is an extremely rare clinically and pathologically distinct subtype of testicular cancer that infrequently metastasizes and typically yields a good prognosis. While retroperitoneal lymphadenopathy in the typical testicular cancer patient often harbors metastatic disease, in a patient with spermatocytic seminoma this finding should be viewed with suspicion, and pathologic confirmation of metastatic disease is essential. We present a 49-year-old man with spermatocytic seminoma and retroperitoneal and mesenteric lymphadenopathy who was found to have concurrent low-grade lymphoma.

Peripheral artery disease is associated with severe impairment of vascular function.

Patients with peripheral artery disease (PAD) have higher cardiovascular event rates than patients with established coronary artery disease (CAD) and abnormal endothelial function predicts cardiovascular risk in PAD and CAD. We investigated the hypothesis that PAD is associated with a greater degree of impairment in vascular function than CAD. We used several non-invasive tests to evaluate endothelial function in 1320 men and women with combined PAD and CAD (n = 198), PAD alone (n = 179), CAD alone (n = 466), or controls aged > 45 years without CAD or PAD (n = 477). Patients with PAD had lower brachial artery flow-mediated dilation (5.1 ± 3.9% PAD and CAD, 5.9 ± 4.4% PAD alone) compared to patients with CAD alone (7.0 ± 4.5%) and no PAD or CAD (8.1 ± 5.1%, p < 0.0001). In multivariable models adjusting for clinical covariates and the presence of CAD, PAD remained associated with lower flow-mediated dilation (p < 0.0001). PAD was associated also with lower nitroglycerin-mediated dilation and reactive hyperemia. Patients with both PAD and CAD had a lower digital pulse amplitude tonometry (PAT) ratio in unadjusted models but not in adjusted models. Flow-mediated dilation was modestly associated with PAT ratio in patients with atherosclerotic disease (r = 0.23, p < 0.0001) but not among control participants (r = 0.008, p = 0.93). Our findings indicate that patients with PAD have greater impairment of vasodilator function and are consistent with the possibility that endothelial dysfunction may contribute to adverse cardiovascular prognosis in PAD.