Prior Infarcts, Reactivity, and Angiography in Moyamoya Disease (PIRAMD): a scoring system for moyamoya severity based on multimodal hemodynamic imaging.

OBJECTIVE Quantification of the severity of vasculopathy and its impact on parenchymal hemodynamics is a necessary prerequisite for informing management decisions and evaluating intervention response in patients with moyamoya. The authors performed digital subtraction angiography and noninvasive structural and hemodynamic MRI, and they outline a new classification system for patients with moyamoya that they have named Prior Infarcts, Reactivity, and Angiography in Moyamoya Disease (PIRAMD). METHODS Healthy control volunteers (n = 11; age 46 ± 12 years [mean ± SD]) and patients (n = 25; 42 ± 13.5 years) with angiographically confirmed moyamoya provided informed consent and underwent structural (T1-weighted, T2-weighted, FLAIR, MR angiography) and hemodynamic (T2*- and cerebral blood flow-weighted) 3-T MRI. Cerebrovascular reactivity (CVR) in the internal carotid artery territory was assessed using susceptibility-weighted MRI during a hypercapnic stimulus. Only hemispheres without prior revascularization were assessed. Each hemisphere was considered symptomatic if localizing signs were present on neurological examination and/or there was a history of transient ischemic attack with symptoms referable to that hemisphere. The PIRAMD factor weighting versus symptomatology was optimized using binary logistic regression and receiver operating characteristic curve analysis with bootstrapping. The PIRAMD finding was scored from 0 to 10. For each hemisphere, 1 point was assigned for prior infarct, 3 points for reduced CVR, 3 points for a modified Suzuki Score ≥ Grade II, and 3 points for flow impairment in ≥ 2 of 7 predefined vascular territories. Hemispheres were divided into 3 severity grades based on total PIRAMD score, as follows: Grade 1, 0-5 points; Grade 2, 6-9 points; and Grade 3, 10 points. RESULTS In 28 of 46 (60.9%) hemispheres the findings met clinical symptomatic criteria. With decreased CVR, the odds ratio of having a symptomatic hemisphere was 13 (95% CI 1.1-22.6, p = 0.002). The area under the curve for individual PIRAMD factors was 0.67-0.72, and for the PIRAMD grade it was 0.845. There were 0/8 (0%), 10/18 (55.6%), and 18/20 (90%) symptomatic PIRAMD Grade 1, 2, and 3 hemispheres, respectively. CONCLUSIONS A scoring system for total impairment is proposed that uses noninvasive MRI parameters. This scoring system correlates with symptomatology and may provide a measure of hemodynamic severity in moyamoya, which could be used for guiding management decisions and evaluating intervention response.

Planning-free cerebral blood flow territory mapping in patients with intracranial arterial stenosis.

A noninvasive method for quantifying cerebral blood flow and simultaneously visualizing cerebral blood flow territories is vessel-encoded pseudocontinuous arterial spin labeling MRI. However, obstacles to acquiring such information include limited access to the methodology in clinical centers and limited work on how clinically acquired vessel-encoded pseudocontinuous arterial spin labeling data correlate with gold-standard methods. The purpose of this work is to develop and validate a semiautomated pipeline for the online quantification of cerebral blood flow maps and cerebral blood flow territories from planning-free vessel-encoded pseudocontinuous arterial spin labeling MRI with gold-standard digital subtraction angiography. Healthy controls (n = 10) and intracranial atherosclerotic disease patients (n = 34) underwent 3.0 T MRI imaging including vascular (MR angiography) and hemodynamic (cerebral blood flow-weighted arterial spin labeling) MRI. Patients additionally underwent catheter and/or CT angiography. Variations in cross-territorial filling were grouped according to diameters of circle of Willis vessels in controls. In patients, Cohen's k-statistics were computed to quantify agreement in perfusion patterns between vessel-encoded pseudocontinuous arterial spin labeling and angiography. Cross-territorial filling patterns were consistent with circle of Willis anatomy. The intraobserver Cohen's k-statistics for cerebral blood flow territory and digital subtraction angiography perfusion agreement were 0.730 (95% CI = 0.593-0.867; reader one) and 0.708 (95% CI = 0.561-0.855; reader two). These results support the feasibility of a semiautomated pipeline for evaluating major neurovascular cerebral blood flow territories in patients with intracranial atherosclerotic disease.

Addition of an iliac/obturator lymph node dissection does not improve nodal recurrence or survival in melanoma.

BACKGROUND: Controversy exists regarding the value and indications for inguinal dissection alone or in combination with an iliac/obturator lymph node dissection for melanoma. STUDY DESIGN: We reviewed patients from a multicenter prospective clinical trial and a single center who underwent inguinal dissection alone or combined with an iliac/obturator dissection for cutaneous melanoma. Analyses were stratified and compared by microscopic or macroscopic (palpable or detected by imaging) disease. RESULTS: The study was composed of 134 patients with a median follow-up of 39 months. Indications for inguinal dissection were microscopic disease in 94 (70%) patients and macroscopic nodal disease in 40 (30%) patients. An iliac/obturator dissection yielded tumor-positive pelvic nodes in 25% vs 55% in the microscopic vs macroscopic groups, respectively (p = 0.10). No risk factors for positive pelvic nodes were identified. For both microscopic and macroscopic disease, addition of an iliac/obturator dissection to an inguinal dissection did not significantly reduce the risk of pelvic nodal recurrence. Five-year overall survival rates for 4 groups were compared: microscopic disease, inguinal dissection alone (72%); microscopic disease, iliac/obturator dissection (68%); macroscopic disease, inguinal dissection alone (51%); and macroscopic disease, iliac/obturator dissection (44%) (p = 0.0163). On survival analysis, addition of an iliac/obturator dissection in either microscopic or macroscopic disease did not affect disease-free survival or regional lymph node recurrence-free survival. CONCLUSIONS: The addition of an iliac/obturator dissection to an inguinal dissection for both microscopic and macroscopic nodal disease did not significantly affect lymph node recurrence rates, disease-free survival, or overall survival.

Prognostic significance of tumor infiltrating lymphocytes in melanoma.

The prognostic significance of tumor infiltrating lymphocyte (TIL) response in cutaneous melanoma is controversial. This analysis of data from a prospective, randomized trial included patients with cutaneous melanoma > or = 1.0 mm Breslow thickness who underwent wide local excision and sentinel lymph node (SLN) biopsy. Univariate and multivariate analyses were performed to determine factors associated with TIL response, disease-free survival (DFS), and overall survival (OS). A total of 515 patients were included; TIL response was classified as "brisk" (n = 100; 19.4%) or "non-brisk" (n = 415; 80.6%). Patients in the nonbrisk TIL group were more likely to have tumor-positive SLN (17.6% vs 7%; P = 0.0087). On multivariate analysis, nonbrisk TIL response, increased tumor thickness, and ulceration were significant independent predictors of tumor-positive SLN. By Kaplan-Meier analysis, 5-year DFS rate was 91 per cent for those with a brisk TIL response compared with 86 per cent in the nonbrisk group (P = 0.41). The 5-year OS rates were 95 per cent versus 84 per cent in the brisk versus nonbrisk TIL groups, respectively (P = 0.0083). However, on multivariate analysis, TIL response was not a significant independent factor predicting DFS or OS. TIL response is a significant predictor of SLN metastasis but is not a major predictor of DFS or OS.

Does mitotic rate predict sentinel lymph node metastasis or survival in patients with intermediate and thick melanoma?

BACKGROUND: The significance of mitotic rate (MR) in melanoma remains controversial. METHODS: In this retrospective analysis of a prospective randomized trial that included patients with melanoma of 1.0 mm or greater, all patients underwent wide excision and sentinel node (sentinel lymph node [SLN]) biopsy. Univariate and multivariate analyses were performed to evaluate factors predictive of disease-free survival (DFS) and overall survival (OS). RESULTS: A total of 551 patients had MR reported. A cut-off point of 6 mitoses/mm(2) best discriminated DFS and OS: 455 patients (82.6%) had MR less than 6/mm(2). SLN were tumor-positive in 14.7% of low MR versus 31.3% of high MR patients (P = .0003). There were significant differences in DFS (P = .0014) and OS (P = .0002) between the 2 groups, however, MR failed to remain significant in the multivariate model. CONCLUSIONS: MR is weakly predictive of SLN status but it is not an independent predictor of survival for melanomas 1.0 mm or thicker.