Hyperpolarized¹³C-Pyruvate Metabolism as a Surrogate for Tumor Grade and Poor Outcome in Renal Cell Carcinoma—A Proof of Principle Study

Differentiating aggressive clear cell renal cell carcinoma (ccRCC) from indolent lesions is challenging using conventional imaging. This work prospectively compared the metabolic imaging phenotype of renal tumors using carbon-13 MRI following injection of hyperpolarized [1-13C]pyruvate (HP-13C-MRI) and validated these findings with histopathology. Nine patients with treatment-naïve renal tumors (6 ccRCCs, 1 liposarcoma, 1 pheochromocytoma, 1 oncocytoma) underwent pre-operative HP-13C-MRI and conventional proton (1H) MRI. Multi-regional tissue samples were collected using patient-specific 3D-printed tumor molds for spatial registration between imaging and molecular analysis. The apparent exchange rate constant (kPL) between 13C-pyruvate and 13C-lactate was calculated. Immunohistochemistry for the pyruvate transporter (MCT1) from 44 multi-regional samples, as well as associations between MCT1 expression and outcome in the TCGA-KIRC dataset, were investigated. Increasing kPL in ccRCC was correlated with increasing overall tumor grade (ρ = 0.92, p = 0.009) and MCT1 expression (r = 0.89, p = 0.016), with similar results acquired from the multi-regional analysis. Conventional 1H-MRI parameters did not discriminate tumor grades. The correlation between MCT1 and ccRCC grade was confirmed within a TCGA dataset (p &lt; 0.001), where MCT1 expression was a predictor of overall and disease-free survival. In conclusion, metabolic imaging using HP-13C-MRI differentiates tumor aggressiveness in ccRCC and correlates with the expression of MCT1, a predictor of survival. HP-13C-MRI may non-invasively characterize metabolic phenotypes within renal cancer.</jats:p

Export market participation with sunk costs and firm heterogeneity

In this article we investigate the importance of sunk costs, firm characteristics and spillovers from nearby exporters on a firm's decision to participate in exporting. The empirical analysis involves the estimation of a nonstructural, discrete choice, dynamic model with firm heterogeneity. By using panel data for Estonian companies from 1994 to 1999 we find that: (i) both sunk costs and observable firm characteristics are important determinants of export market participation; (ii) previous history matters, in that, if a firm has been exporting the previous period or the period before, it significantly increases the likelihood of the firm exporting in the current period; (iii) larger firms with high capital intensity and foreign ownership are more likely to be exporters; (iv) operating in an export-oriented industry increases a firm's likelihood of exporting.

Role of preoperative MR imaging in the evaluation of patients with persistent or recurrent gynaecological malignancies before pelvic exenteration

PURPOSE: To determine the diagnostic performance of MRI in assessing local tumour extent and evaluate associations between MRI features and survival in patients undergoing MRI before pelvic exenteration for persistent or recurrent gynaecological cancers. METHODS AND MATERIALS: The study included 50 patients with persistent or recurrent gynaecological malignancies who underwent pelvic exenteration between January 1999 and December 2011 and had MRI at most 90 days before surgery. Two radiologists independently assessed invasion of adjacent organs (on a 5-point scale). Diagnostic accuracy, inter-reader agreement, and associations between organ invasion on MRI and patient survival were evaluated. RESULTS: Areas under receiver operating characteristic curves (AUCs) for invasion of the bladder, rectum and pelvic sidewall were 0.96, 0.90 and 0.98 for reader 1 and 0.95, 0.88 and 0.90 for reader 2. Corresponding sensitivities/specificities were 87.0 %/92.6 %, 81.3 %/97.0 % and 87.5 %/97.2 % for reader 1, and 87.0 %/100.0 %, 75.0 %/97.0 % and 75.0 %/94.4 % for reader 2. Inter-reader agreement was excellent for organ invasion (κ = 0.81-0.85). Pelvic sidewall invasion on MRI was associated with overall and recurrence-free survival (P = 0.01-0.04 for the two readers). CONCLUSION: Preoperative MRI is accurate in predicting organ invasion. It may guide surgical planning and serve as a predictive biomarker in patients undergoing pelvic exenteration for gynaecological malignancies. KEY POINTS: • MRI can accurately assess bladder and rectal wall invasion before major surgery. • MRI identifies patients requiring extended pelvic exenteration by detecting sidewall invasion. • Inter-reader agreement for detecting organ invasion and tumor size is excellent. • Pelvic sidewall invasion on MRI is associated with shorter overall and recurrence-free survival