CT Attenuation Values Do Not Reliably Distinguish Benign Sclerotic Lesions From Osteoblastic Metastases in Patients Undergoing Bone Biopsy.

BACKGROUND. CT attenuation thresholds that accurately distinguish enostoses from untreated osteoblastic metastases have been published. In the Mayo Clinic practices, these thresholds have been applied more broadly to distinguish benign sclerotic bone lesions other than enostoses from osteoblastic metastases. OBJECTIVE. The purpose of this article is to determine if CT attenuation thresholds allow the distinguishing of benign sclerotic bone lesions from osteoblastic metastases in patients undergoing bone biopsy. METHODS. A retrospective search was conducted to identify sclerotic lesions described on CT between October 7, 1998, and July 15, 2018, that underwent subsequent biopsy. Two musculoskeletal radiologists recorded lesions' maximum and mean attenuation. Using previously published attenuation thresholds, sensitivity and specificity for differentiating benign sclerotic lesions from osteoblastic metastases were calculated. ROC curve analysis was performed to determine if more appropriate attenuation thresholds exist. Intraclass correlation coefficients (ICCs) were computed. RESULTS. A total of 280 patients met inclusion criteria. Of those, 162 had malignant biopsy results and 118 had benign biopsy results. Of the 162 malignant lesions, 81 had received prior treatment. Maximum and mean attenuation were not significantly different between benign and malignant lesions for either reader (all p > .05). For reader 1, to distinguish benign from malignant lesions, a maximum attenuation threshold of more than 1060 HU resulted in sensitivity of 23.7%, specificity of 87.0%, and accuracy of 60.6%. A mean attenuation threshold of greater than 885 HU resulted in sensitivity of 19.5%, specificity of 90.7%, and accuracy 60.7%. ROC curve analysis showed AUCs for mean and maximum attenuation thresholds of 51.8% and 54.6%, respectively. Subgroup analyses of benign versus malignant and treated versus untreated lesions had similar results. Similar findings were obtained for reader 2. The two readers' ICC was 0.946 for maximum attenuation and 0.918 for mean attenuation. CONCLUSION. Published attenuation thresholds for distinguishing enostoses from osteoblastic metastases had slightly decreased specificity and markedly decreased sensitivity when applied to the differentiation of benign sclerotic lesions from osteoblastic metastases in our sample of biopsy-proven lesions. ROC analysis showed no high-performing attenuation threshold alternative. CLINICAL IMPACT. Published CT attenuation thresholds intended for distinguishing enostoses from osteoblastic metastases should not be used more broadly. More accurate alternative thresholds could not be derived.

Left Ventricular Assist Device Therapy and Acute Pancreatitis: Higher Incidence and Worse Clinical Outcomes.

OBJECTIVE: The aim of the study was to compare incidence and outcomes of acute pancreatitis among advanced heart failure therapies. METHODS: Two retrospective cohorts are as follows: A, patients with heart failure presenting to our hospitals and B, the US National Inpatient Sample. Three groups were compared: left ventricular assist device (LVAD) recipients, transplant recipients, and controls who did not qualify for advanced therapies. Primary outcomes were pancreatitis incidence and mortality. Secondary outcomes included kidney failure, multiorgan failure, shock, and health care utilization. RESULTS: Cohort A included 1344 heart failure patients, and cohort B included 677,905 patients with acute pancreatitis. In cohort A, annual pancreatitis incidence was 6.7 cases per 1000 LVAD recipients, 4.1 per 1000 LVAD bridge-to-transplant, 2.3 per 1000 transplant recipients, and 3.2 per 1000 heart failure controls (P = 0.03). Combined, the incidence was 5.6 per 1000 LVAD users and 2.7 in 1000 non-LVAD users (relative risk, 2.1; P = 0.009). In cohort B, increased mortality was seen in LVAD users, but not in transplant recipients. Left ventricular assist device patients had higher odds of kidney failure, multiorgan failure, shock, and intensive care. CONCLUSIONS: Patients with LVAD have double risk of pancreatitis, worse clinical outcomes, and increased healthcare utilization. Studies elucidating the mechanisms behind pancreatic injury in advanced heart failure are suggested.

Trastuzumab and pertuzumab in circulating tumor DNA ERBB2-amplified HER2-positive refractory cholangiocarcinoma.

Cholangiocarcinoma is a heterogeneous and target-rich disease with differences in actionable targets. Intrahepatic and extrahepatic types of cholangiocarcinoma differ significantly in clinical presentation and underlying genetic aberrations. Research has shown that extrahepatic cholangiocarcinoma is more likely to be associated with ERBB2 (HER2) genetic aberrations. Various anti-HER2 clinical trials, case reports and other molecular studies show that HER2 is a real target in cholangiocarcinoma; however, anti-HER2 agents are still not approved for routine administration. Here, we show in a metastatic cholangiocarcinoma with ERBB2 amplification identified on liquid biopsy (circulating tumor DNA (ctDNA) testing), a dramatic response to now over 12 months of dual-anti-HER2 therapy. We also summarize the current literature on anti-HER2 therapy for cholangiocarcinoma. This would likely become another treatment option for this target-rich disease.

Assessment of DNA Damage After Ionizing Radiation Exposure in Patients Undergoing Cardiac Resynchronization Therapy Device Implantation or Atrial Fibrillation Ablation (The RADAR Study).

BACKGROUND: There is limited data regarding effect of prolonged radiation exposure during electrophysiological (EP) procedures on direct DNA damage. Comet test has shown to assess DNA damage following radiation exposure. METHODS: We performed a single-center prospective observational study assessing direct DNA damage using the quantitative comet assay in patients undergoing cardiac resynchronization (CRT) and atrial fibrillation (AF) catheter ablation procedures. Venous comet assay was performed pre, immediately post procedure and at 3-month duration in twenty-two (N=22) patients who underwent catheter ablation for symptomatic AF and fourteen (N=14) patients who underwent CRT implantation. RESULTS: The median [interquartile range (IQR)] fluoroscopy time, radiation dose and dose area product (DAP) were 34.3 (27.97 - 45.48) minutes, 853.07 (611.36 - 1334.76) mGy and 16,994.10 (9,023.65 - 58,845.00) UGym2 in the ablation group and 30.05 (18.75 - 37.33) minutes, 345.00 (165.09 - 924.79) mGy and 11,837.20 [7182.67 - 35567.75] UGym2 in the CRT group. When compared with pre-procedure, there was a statistically significant increase in median (IQR) DNA migration on comet assay in the ablation group immediately post procedure [+6.55 µm (0.78, 10.25, p=0.02)] that subsequently decreased at 3 months [-1.00 µm (-2.20, 0.78), p=0.03] but not in the CRT group. CONCLUSION: There was a significant increase in DNA damage as detected by comet assay immediately post procedure that normalized at 3 months in patients undergoing AF ablation. Further large prospective studies are warranted to evaluate the impact of this prolonged radiation exposure and DNA damage on long-term follow up.