Shifting perspectives in coronary involvement of polyarteritis nodosa: case of 3-vessel occlusion treated with 4-vessel CABG and review of literature.

BACKGROUND: Polyarteritis Nodosa (PAN) is a systemic vasculitis (SV) historically thought to spare the coronary arteries. Coronary angiography and contemporary imaging reveal coronary stenosis and dilation, which are associated with significant morbidity and mortality. Coronary arteries in PAN are burdened with accelerated atherosclerosis from generalized inflammation adding to an inherent arteritic process. Traditional atherosclerotic risk factors fail to approximate risk. Few reports document coronary pathology and optimal therapy has been guarded. METHODS: Database publication query of English literature from 1990-2022. RESULTS: Severity of coronary involvement eludes laboratory monitoring, but coronary disease associates with several clinical symptoms. Framingham risk factors inadequately approximate disease burden. Separating atherosclerosis from arteritis requires advanced angiographic methods. Therapy includes anticoagulation, immunosuppression and revascularization. PCI has been the mainstay, though stenting is confounded by vagarious alteration in luminal diameter and reports of neointimization soon after placement. CONCLUSIONS: When graft selection avoids the vascular territory of SV's, CABG offers definitive therapy. We have contributed report of a novel CABG configuration in addition to reviewing, updating and discussing the literature. Accumulating evidence suggests discrete clinical symptoms warrant suspicion for coronary involvement.

The association between left main coronary artery calcium and cardiovascular-specific and total mortality: The Coronary Artery Calcium Consortium.

BACKGROUND AND AIMS: Left main (LM) coronary artery disease is associated with greater myocardial infarction-related mortality, however, coronary artery calcium (CAC) scoring does not account for disease location. We explored whether LM CAC predicts excess mortality in asymptomatic adults. METHODS: Cause-specific cardiovascular and all-cause mortality was studied in 28,147 asymptomatic patients with non-zero CAC scores in the CAC Consortium. Multivariate regression was performed to evaluate if the presence and burden of LM CAC predict mortality after adjustment for clinical risk factors and the Agatston CAC score. We further analyzed the per-unit hazard associated with LM CAC in comparison to CAC in other arteries. RESULTS: The study population had mean age of 58.3 ±â€¯10 years and CAC score of 301 ±â€¯631. LM CAC was present in 21.7% of the cases. During 312,398 patient-years of follow-up, 1,907 deaths were observed. LM CAC was associated with an increased burden of clinical risk factors and total CAC, and was independently predictive of increased hazard for all-cause (HR 1.2 [1.1, 1.3]) and cardiovascular disease death (HR 1.3 [1.1, 1.5]). The hazard for death increased proportionate to the percentage of CAC localized to the LM. On a per-100 Agatston unit basis, LM CAC was associated with a 6-9% incremental hazard for death beyond knowledge of CAC in other arteries. CONCLUSIONS: The presence and high burden of left main CAC are independently associated with a 20-30% greater hazard for cardiovascular and total mortality in asymptomatic adults, arguing that LM CAC should be routinely noted in CAC score reports when present.

In vitro biologic efficacy of sunitinib drug-eluting beads on human colorectal and hepatocellular carcinoma-A pilot study.

PURPOSE: Sunitinib drug eluting beads (DEB) are a novel anti-angiogenic bead preparation for use in transarterial chemoembolization. However, systematic studies of sunitinib DEB's effect on cancer cells have not been reported. Herein, we assess their direct biologic efficacy against carcinoma cell lines and correlate cell viability with drug release in vitro. MATERIALS AND METHODS: Sunitinib-HCl (10mg/mL) in Milli-Q water was mixed with LC Bead® 300-500µm (Biocompatibles UK Ltd.). Loading and release were assessed by measurement of drug UV absorbance using UV-visible spectrophotometer. Viability of human colorectal cancer (CRC, HCT116 and HT29) and hepatocellular carcinoma (HCC, HepG2) cells upon exposure to sunitinib DEB was measured using a bioluminescent assay. Drug concentration during exposure was quantified using HPLC. RESULTS: When added to cultured HepG2 cells, sunitinib DEB rapidly inhibited viability with a significant decrease observed within 1 hour of incubation. Viability of HCT116 and HT29 cells decreased relatively slower, with significant reductions observed after 8 and 24 hours, respectively. After 24 hours there was nearly complete inhibition of all three cell lines. There was no difference in viability observed between cells treated with 5 µl, 10 µL, or 20 µL of sunitinib DEB. HPLC analysis of the cell culture supernatant demonstrated saturation of the cell medium within approximately 4 hours for each amount added, with sunitinib achieving a final concentration of 17.61 µM (SE ±1.01). CONCLUSIONS: Sunitinib can be efficiently loaded to and released from LC beads, and the resulting sunitinib DEB demonstrate strong in vitro inhibition of human CRC and HCC cells.

Connecting cancer biology and clinical outcomes to imaging in KRAS mutant and wild-type colorectal cancer liver tumors following selective internal radiation therapy with yttrium-90.

PURPOSE: To determine whether pathologic colorectal tumor KRAS mutation status is correlated with progression-free survival (PFS) by imaging after selective internal radiation therapy with Yttrium-90 (SIRT Y90) for metastatic colorectal cancer in the liver (mCRC). MATERIALS AND METHODS: This was an IRB approved, HIPAA compliant retrospective cohort study. Consecutive patients with unresectable mCRC with documented KRAS mutation status treated at a single center from 2002 to 2013 with SIRT Y90 were investigated. Treatment response was compared between KRAS wild-type (wt) and mutant (mut) using an anatomic tumor response criteria based on RECIST 1.0. Kaplan-Meier estimation and Cox regression analysis were used to measure progression-free survival (PFS) and to assess independent prognostic factors for PFS. RESULTS: 82 of 186 patients met review criteria. 33 (40.2%) patients were identified as KRAS mut. PFS was longer in KRAS wt (median 166 days [95% CI 96-258 days]) vs. mut (median 91 days [95% CI 79-104 days], p = 0.002). KRAS mut patients were 1.48 times more likely to progress at first follow-up imaging than wt (95% CI 1.06-2.08, p = 0.024). Univariate analysis identified high pre-SIRT Y90 INR, KRAS wt, any use of anti-EGFR therapy, and post-SIRT Y90 chemotherapy as prognostic factors for longer PFS. In multivariate analysis, only KRAS wt was an independent prognostic factor for longer PFS (RR: 1.80 [95% CI 1.08-2.99], p = 0.024). CONCLUSION: Longer PFS is associated with KRAS wt vs. mut following SIRT Y90.

90Y Radioembolization Lung Shunt Fraction in Primary and Metastatic Liver Cancer as a Biomarker for Survival.

OBJECTIVE: The aim of this study was to investigate pre-90Y lung shunt fraction (LSF) as a prognostic factor for overall survival (OS) in 90Y (resin/glass) planning 99mTc-MAA hepatopulmonary shunt studies for primary (hepatocellular carcinoma [HCC], intrahepatic cholangiocarcinoma) and metastatic liver tumors. METHODS: A total of 366 consecutive patients with primary and metastatic liver tumors underwent pre-90Y shunt study and 90Y radioembolization (mean age, 59.2 years; 55% were male). MAA (mean activity, 3.65 mCi) was administered via the proper hepatic artery. Shunted lung activity was obtained by planar scintigraphy. Median LSF values for primary tumors and metastases were compared with OS from first 90Y therapy via Kaplan-Meier estimation and log-rank test. Correlations between LSF and tumor involvement on baseline cross-sectional imaging were analyzed using Pearson coefficient (r). Patients with LSF of greater than 20% were deemed unsuitable for 90Y. RESULTS: The study included 79 (21.5%) colorectal, 73 (20%) neuroendocrine, 70 (19.1%) HCC, 40 (10.9%) intrahepatic cholangiocarcinoma, 40 (10.9%) melanoma, 20 (5.5%) breast, and 44 (12%) other tumors including lung and pancreatic cancers. Lung shunt fractions of less than 10% and 10% to 20% were observed in 235 patients (64.2%) and 131 patients (35.8%), respectively. Median LSFs were as follows: colorectal cancer (7.60%), neuroendocrine tumor (7.01%), HCC (11.47%), cholangiocarcinoma (7.00%), melanoma (6.00%), breast cancer (7.00%), and others, including lung and pancreatic metastases to the liver (8.36%). The HCC median LSF was significantly higher than that in non-HCC tumors, 11.47% versus 7.10% (P < 0.001). High LSF (≥ 10%) in HCC correlated with poorer survival from first 90Y compared with low LSF (<10%; 4.5 vs 16.4 months, P = 0.003). Similarly, for metastatic disease, high LSF demonstrated significantly poorer survival compared with low LSF in colorectal liver metastases (13.5 vs 7.0 months, P = 0.013), neuroendocrine liver metastases (33.0 vs 9.1 months, P < 0.001), and melanoma liver metastases (12.0 vs 5.0 months, P = 0.03). No correlation between tumor burden on cross-sectional imaging and LSF was observed (r = 0.35). CONCLUSIONS: In patients who are candidates for 90Y therapy, higher LSF is a poor prognostic factor for OS in HCC and metastatic liver tumors.

KRAS Status as an Independent Prognostic Factor for Survival after Yttrium-90 Radioembolization Therapy for Unresectable Colorectal Cancer Liver Metastases.

PURPOSE: To evaluate Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation status as a prognostic factor for survival after yttrium-90 ((90)Y) radioembolization for colorectal cancer (CRC) liver metastases. MATERIALS AND METHODS: Consecutive patients with unresectable CRC liver metastases and documented KRAS mutation status who were treated with (90)Y radioembolization during the period 2007-2014 were investigated. Patient demographics, disease characteristics, therapy regimens, and overall survival (OS) from first (90)Y radioembolization were compared between patients with KRAS wild-type (wt) and mutant status. Kaplan-Meier estimation and Cox regression were used for survival analysis and to assess independent prognostic factors for OS. RESULTS: Of 186 patients, 104 underwent KRAS mutation analysis before (90)Y radioembolization, with 45 (43.3%) identified as mutant. The wt and mutant groups were similar in demographics, liver status, overall performance status, and tumor characteristics (all P > .05). Mean time from liver metastasis to (90)Y radioembolization was greater in patients with KRAS wt status (P = .033). A greater percentage of wt patients received anti-epidermal growth factor receptor therapies before (90)Y radioembolization (66.1% vs 8.9%; P < .001). Median OS from first (90)Y radioembolization was significantly greater in KRAS wt patients (9.5 mo vs 4.8 mo; P = .041). Univariate analysis identified Child-Pugh class, carcinoembryonic antigen (CEA), chemotherapy after (90)Y radioembolization, KRAS status, and treatment-induced toxicity as prognostic factors for OS. Multivariate Cox regression analysis demonstrated Child-Pugh class, CEA, and KRAS status to be independent prognostic factors for OS, even when correcting for the effect of chemotherapy after (90)Y radioembolization. CONCLUSIONS: Patients with CRC and KRAS wt may derive greater survival benefit from (90)Y radioembolization therapy than patients with KRAS mutant.