Purpose Desmoplastic stroma is a cardinal feature of primary pancreatic ductal adenocarcinoma (PDA), but its effects on the biology, prognosis, and therapeutic outcomes in the disease are not known. We developed an automated method to assess tumor stroma density (TSD) and investigated computed tomography (CT) correlates of stroma in PDA. Patients and Methods We collected PDA samples from rapid autopsy and resection series and digitally annotated samples to quantify TSD. A series of patients who had undergone resection also underwent preoperative multiphasic CT imaging. Results Automated and manual assessments of TSD were highly correlated (ρ = 0.65; P < .001). Solid organ metastases had a lower median TSD than primary tumors ( P < .001). Patients whose tumors had high TSD had prolonged recurrence-free survival (hazard ratio [HR] = 0.51; P = .003) and overall survival (HR = 0.57; P = .008). In another independent dataset, patients whose tumors had high TSD had decreased risk for recurrence (HR = 0.03; P = .003) and death (HR = 0.03; P = .003) at time of resection; however, the protective effect of high TSD diminished over time. Patients with a normalized portovenous phase CT tumor enhancement ratio ≥ 0.40 had a longer time to recurrence after resection ( P = .020). Normalized portovenous phase CT tumor enhancement ratio was significantly correlated with TSD ( P = .003). Conclusion Objective quantitative assessment of stroma in PDA revealed several clinically relevant observations. Stroma was less abundant in metastatic PDA, the primary cause of mortality associated with PDA. High stromal content correlated with favorable outcome in patients with resected tumors, implying a protective effect of stroma and suggesting careful consideration of active stromal depletion therapies. Standard, multiphase CT imaging correlated with stroma content and clinical outcome, indicating that noninvasive assessment of stroma is a feasible sensitivity enrichment approach in PDA.

Acute kidney injury (AKI) is a major risk factor for the development of chronic kidney disease (CKD). Persistent oxidative stress and mitochondrial dysfunction are implicated across diverse forms of AKI and in the transition to CKD. In this study, we applied hyperpolarized (HP) 13C dehydroascorbate (DHA) and 13C pyruvate MR spectroscopy to investigate the renal redox capacity and mitochondrial pyruvate dehydrogenase (PDH) activity, respectively, in a murine model of AKI at baseline, and 7 days after unilateral ischemia reperfusion injury (IRI). Compared to the contralateral sham-operated kidneys, the kidneys subjected to IRI showed a significant decrease in the HP 13C Vitamin C/(Vitamin C+DHA) ratio, consistent with a decrease in redox capacity. The kidneys subjected to IRI also showed a significant decrease in the HP 13C bicarbonate/pyruvate ratio, consistent with impaired PDH activity. The IRI kidneys showed a significantly higher HP 13C lactate/pyruvate ratio at day 7 compared to baseline, although the 13C lactate/pyruvate ratio was not significantly different between the IRI and the contralateral sham-operated kidneys at day 7. Arterial spin labeling MRI demonstrated significantly reduced perfusion in the IRI kidneys. Renal tissue analysis showed corresponding increased reactive oxygen species (ROS), and reduced PDH activity in the IRI kidneys. Our results show the feasibility of HP 13C MR for the noninvasive assessment of oxidative stress and mitochondrial PDH activity following renal ischemia reperfusion injury.

Purpose: To investigate the safety and effectiveness of transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) patients with HIV infection. Materials: Ninety TACE procedures (60 conventional TACE, 30 drug-eluting bead TACE) in 31 HIV-positive patients (all men; mean age 57 years; mean CD4 340, 100% on antiretroviral therapy) performed between September 2006 and August 2017 were examined as a part of retrospective study. Risk factors for HCC included chronic hepatitis C (61%), chronic hepatitis B (26%), and multifactorial (13%). Median baseline total bilirubin was 1.1 mg/ dL (range, 0.3-3.7). Mean MELD and Child-Pugh scores prior to TACE were 12 (range, 6-28) and 7 (range, 5-9), respectively. Baseline alpha fetoprotein (AFP) prior to any TACE procedure was less than 10 μg/L in 22% of patients, between 10 and 100 μg/L in 43%, and greater than 100 μg/L in 35%. For 18 patients (58%) TACE was performed for HCC within Milan Criteria as a "bridge" to liver transplant; 5 patients (16%) underwent TACE in an attempt to downstage into Milan Criteria, while 8 patients (26%) underwent TACE for palliative purposes. For each procedure, laboratory and clinical adverse events and response rates were assessed. Overall survival (OS) and transplant rates were also determined. Results: Symptoms of post-embolization syndrome were reported after 46% of TACE procedures. New or worsening hyperbilirubinemia was the most common postprocedure laboratory abnormality (58%). One infectious complication (urinary tract infection) occurred within 1 month of TACE. Complete response and partial response on follow-up cross sectional imaging was noted after 34% and 52% of TACE procedures, respectively. Of 21 eligible transplant candidates, 14 received transplants and 3 remain listed. Of transplant recipients, mean survival or follow-up was 55 months (range, 8-134, 3 transplant recipients deceased). Mean OS for patients not on the transplant list was 16 months from initial treatment, with a mean 3.4 treatment sessions (range, 1-7) per patient. Conclusions: TACE is a safe and effective treatment for HCC in patients with HIV infection.

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1322 days), 125 patients received post-TACE imaging prior to transplant. Results: Recurrence occurred in 9 patients (mean time from transplant, 526 days). Poor treatment response (SD/DP) accounted for 67% (6/9) cases of recurrence and was present in 18% (23/125) of patients prior to transplant (p ¼ 0.0008). When mRECIST categories are further stratified, recurrence was seen in 1.4% (1/71) CR vs 6.5% (2/31) PR vs 18.8% (3/16) SD vs 43% (3/7) DP prior to transplant (p ¼ 0.0025). Mixed HCC/ cholangiocarcinoma tumors at explant (p ¼ 0.004), higher tumor grade at explant (p ¼ 0.04), and lymphovascular invasion at explant (p ¼ 0.007) were also associated with increased incidence of posttransplant recurrence. While a trend in increased pretreatment tumor size and posttranspant recurrence was identified (3.3 cm vs 2.7 cm, p ¼ 0.09), no additional pretransplant variable was identified to suggest an association with posttransplant recurrence in patients who were treated with TACE prior to transplant. Conclusions: Many models have recently been proposed to help identify the risk of posttransplant recurrence in patients with HCC. However, these models are limited by their posttransplant predictive ability. TACE response prior to transplant highlights patients at risk for posttransplant recurrence and could play an important role in liver transplant allocation.

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