Comparison of abdominal MRI with diffusion-weighted imaging to 68Ga-DOTATATE PET/CT in detection of neuroendocrine tumors of the pancreas.

PURPOSE: The aim of the study was to evaluate contrast-enhanced MRI, diffusion-weighted MRI (DW MRI), and (68)Ga-DOTATATE positron emission tomography (PET)/CT in the detection of intermediate to well-differentiated neuroendocrine tumors (NET) of the pancreas. METHODS: Eighteen patients with pathologically proven pancreatic NET who underwent MRI including DW MRI and PET/CT within 6 weeks of each other were included in this retrospective study. Two radiologists evaluated T2-weighted (T2w), T2w + DW MRI, T2w + contrast-enhanced T1-weighted (CE T1w) MR images, and PET/CT for NET detection. The sensitivity and level of diagnostic confidence were compared among modalities using McNemar's test and a Wilcoxon signed rank test. Apparent diffusion coefficients (ADC) of pancreatic NETs and normal pancreatic tissue were compared with Student's t test. RESULTS: Of the NETs, 8/23 (34.8 %) and 9/23 (39.1 %) were detected on T2w images by observers 1 and 2, respectively. Detection rates improved significantly by combining T2w images with DW MRI (observer 1: 14/23 = 61 %; observer 2: 15/23 = 65.2 %; p < 0.05) or CE T1w images (observer 1: 14/23 = 61 %; observer 2: 15/23 = 65.2 %; p < 0.05). Detection rates of pancreatic NET with PET/CT (both observers: 23/23 = 100 %) were statistically significantly higher than with MRI (p < 0.05). The mean ADC value of NET (1.02 ± 0.26 × 10(-3) mm(2)/s) was statistically significantly lower than that of normal pancreatic tissue (1.48 ± 0.39 × 10(-3) mm(2)/s). CONCLUSION: DW MRI is a valuable adjunct to T2w imaging and comparable to CE T1w imaging in pancreatic NET detection, quantitatively differentiating between NET and normal pancreatic tissue with ADC measurements. (68)Ga-DOTATATE PET/CT is more sensitive than MRI in the detection of pancreatic NET.

In vivo confocal microscopy of corneal small fiber damage in diabetes mellitus.

BACKGROUND: Advanced diabetic keratopathy includes impaired corneal sensation, reduced tear secretion, conjunctival squamous metaplasia, and goblet cell loss, as well as susceptibility to corneal erosions and ulcerations. It is thought to be a form of generalized diabetic neuropathy. Early diagnosis of nerve fiber degeneration is essential to prevent further damage. METHODS: We examined the corneal innervation pattern of patients with diabetes mellitus type 1 and 2 of various durations by in vivo confocal microscopy, and correlated our findings to the severity of diabetic retinopathy, corneal sensation, peripheral diabetic neuropathy in the lower limb, and nephropathy. RESULTS: Nerve fiber length (NFL) was significantly different between patients without diabetic retinopathy and controls (p = 0.028). In patients with non-proliferative diabetic retinopathy (NPDR) and patients with proliferative diabetic retinopathy (PDR), nerve fiber parameters including density (NFD), NFL, and corneal nerve branching (NB) showed a difference with increasing significance compared to healthy persons. A history of nephropathy and/or peripheral neuropathy (all p < 0.001), decreased corneal sensation (all p < or = 0.03), and pathological vibration sensation (p < or = 0.04) were significantly associated with a decrease in NFD, NFL, and NB (except vibration sensation). Unexpectedly, diabetic patients with normal corneal and vibration sensation demonstrated significant changes in NFD (p = 0.005), NFL, and NB (both p = 0.001) compared to healthy volunteers with intact corneal and vibration sensation. CONCLUSION: Confocal microscopy is a valuable tool for demonstrating subtle corneal nerve alterations in vivo. It is capable of demonstrating diabetic nerve fiber damage earlier than corneal sensation testing and vibration perception assessment in the lower limb.

Prognostic factors and outcomes in metastatic uveal melanoma treated with programmed cell death-1 or combined PD-1/cytotoxic T-lymphocyte antigen-4 inhibition.

BACKGROUND: Uveal melanoma (UM) is an ocular malignancy with high potential for metastatic spread. In contrast to cutaneous melanoma, immunotherapy has not yet shown convincing efficacy in patients with UM. Combined immune checkpoint blockade with checkpoint programmed cell death-1 (PD-1) and checkpoint cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibition has not been systematically assessed for UM to date. PATIENTS AND METHODS: Patients with metastatic UM treated with either PD-1 inhibitor monotherapy or combined PD-1 inhibitor and ipilimumab (an anti-CTLA-4 monoclonal antibody) were included from 20 German skin cancer centres. Records from 96 cases were analysed for treatment outcomes. Clinical and blood parameters associated with overall survival (OS) or treatment response were identified with multivariate Cox regression and binary logistic regression. RESULTS: Eighty-six patients were treated with PD-1 inhibitors only (n = 54 for pembrolizumab, n = 32 for nivolumab) with a centrally confirmed response rate of 4.7%. Median OS was 14 months for pembrolizumab-treated and 10 months for nivolumab-treated patients (p = 0.765). Fifteen patients were treated with combined immune checkpoint blockade with partial response observed in two cases. Median OS was not reached in this group. Multivariate Cox regression identified Eastern Cooperative Oncology Group (ECOG) performance status (p = 0.002), elevated serum levels of lactate dehydrogenase (LDH) (p = 0.002) and C-reactive protein (CRP) (p = 0.001), and a relative eosinophil count (REC) <1.5% (p = 0.002) as independent risk factors for poor survival. Patients with elevated CRP and LDH and a REC <1.5% were at highest risk for disease progression and death (p = 0.001). CONCLUSIONS: Blood markers predict survival in metastatic UM treated with immune checkpoint blockade. Normal serum levels of LDH and CRP and a high REC may help identify patients with better prognosis.

The role of diffusion-weighted MRI in assessment of inflammatory bowel disease.

AIM: To evaluate the role of diffusion-weighted MRI (DW-MRI) in detecting and differentiating acute from chronic bowel inflammation in patients with Crohn's disease (CD). MATERIALS AND METHODS: MR-enteroclysis examinations with DW-MRI were reviewed from 24 patients with histologically proven CD. Segments of bowel were evaluated for acute and chronic inflammation in three different reviews of the MRI images: T2w alone, T2w + DWI, and T2w + CET1w. Mean ADC values of normal bowel segments, as well as bowel segments with acute and chronic inflammation were calculated and compared. Analyses of receiver-operating characteristic (ROC) curve were performed. RESULTS: Hundred and forty four bowel segments in total were reviewed. Inflammation was present in 45 segments. Acute inflammation was present in 31 segments, chronic inflammation in 14. 98 bowel segments showed no inflammatory activity. Sensitivity and specificity for differentiation between normal and inflamed bowel segments was 0.6, 0.67, and 0.80 on T2w, T2w + DWI, and T2w + CET1w datasets, respectively. Specificities for differentiation between normal and inflamed bowel segments were 0.96, 0.96, and 0.98. Sensitivities for differentiation between acute and chronically inflamed bowel segments were 0.85, 0.91, and 0.96, and specificities were 0.88, 0.89, and 1.0, respectively. The mean ADC value of normal bowel (2.18 ± 0.37 × 10(-3) mm(2)/s) was statistically significantly greater than the mean value of inflamed bowel segments (p < 0.001). The mean ADC value of acutely inflamed bowel segments was statistically significantly lower than that of chronically inflamed bowel segments (1.09 ± 0.18 × 10(-3) vs. 1.55 ± 0.21 × 10(-3) mm(2)/s) (p < 0.001). Estimated area under the ROC curve for the diagnosis of acute vs. chronic inflammation was 0.950. A threshold of ADC value of 1.41 × 10(-3) mm(2)/s was optimal for calculation of sensitivity and specificity. CONCLUSION: DW-MRI improves detection and differentiation of acute vs. chronic inflammatory changes of the bowel in patients with CD compared to T2w-images alone.