Limited Value of Ga-68-DOTATOC-PET-CT in Routine Screening of Patients with Multiple Endocrine Neoplasia Type 1.

BACKGROUND: Routine screening is recommended for patients with multiple endocrine neoplasia type 1 (MEN1) to enable early detection and treatment of associated neuroendocrine neoplasms (NEN). Gallium68-DOTATOC-Positron emission tomography combined with computed tomography (Ga-68-DOTATOC-PET-CT) is a very sensitive and specific imaging technique for the detection of sporadic neuroendocrine tumors. The present study evaluated the value of Ga-68-DOTATOC-PET-CT in routine screening of patients with MEN1. METHODS: Between January 2014 and March 2016, all MEN1 patients underwent Ga-68-DOTATOC-PET-CT in addition to conventional imaging (computed tomography of the thorax, magnetic resonance imaging of the abdomen and pituitary, endoscopic ultrasonography). The diagnostic yield of conventional imaging and Ga-68-DOTATOC-PET-CT was prospectively documented and compared, and treatment changes caused by the addition of Ga-68-DOTATOC-PET-CT were recorded. RESULTS: Conventional imaging detected 145 NENs, mainly pancreaticoduodenal NENs (n = 117, 81%), in 31 of 33 MEN1 patients. Ga-68-DOTATOC-PET-CT detected 55 NENs in 23 of the 33 patients (p = 0.0001). Ninety (62%) NENs detected by conventional imaging were missed by DOTATOC-PET-CT. The majority of missed lesions were pNEN (n = 68; 74%). The sensitivity of Ga-68-DOTATOC-PET-CT for NENs <5, 5-9, 10-19 and ≥20 mm was 0, 29, 81 and 100%, respectively. However, Ga-68-DOTATOC-PET-CT detected more liver and lymph node metastases in patients with known metastatic disease, which did not lead to a change of patients' management. In one patient (3%), Ga-68-DOTATOC-PET-CT was the only imaging modality that detected a small intestine NEN and led to potentially curative surgery. CONCLUSION: Ga-68-DOTATOC-PET-CT cannot be recommended for routine screening of MEN1 patients. It might provide important additional information in patients with suspected or known metastatic disease.

Contrast-enhanced CT imaging in patients with chronic kidney disease.

Renal microvascular rarefaction characterizes chronic kidney disease (CKD). In murine models of CKD, micro-CT imaging reflected capillary rarefaction using quantification of renal relative blood volume (rBV). In addition, micro-CT imaging revealed morphological alterations of the intrarenal vasculature including reduced vascular branching and lumen diameter. Here, we retrospectively quantified rBV in contrast-enhanced CT angiography in patients and found that, compared to non-CKD patients, those with CKD and renal fibrosis had significantly reduced rBV in the renal cortex. rBV values closely mirrored capillary rarefaction in the corresponding nephrectomy specimens. In patients with follow-up CT angiography, reduction of renal function was paralleled by a decline in rBV. Using virtual autopsy, i.e., postmortem CT angiography, morphometry of intrarenal arteries in 3D-rendered CT images revealed significantly reduced arterial diameter and branching in CKD compared to non-CKD cases. In conclusion, in CKD patients, contrast-enhanced CT imaging with quantification of rBV correlates with functional renal vasculature, whereas virtual autopsy allows morphometric analyses of macrovascular changes. Importantly, the observed vascular alterations in CKD patients mirror those in animals with progressive CKD, suggesting a high relevance of animal models for studying vascular alterations in CKD and renal fibrosis.

Bronchopulmonary Neuroendocrine Neoplasms and Their Precursor Lesions in Multiple Endocrine Neoplasia Type 1.

OBJECTIVE: The prevalence and clinical behavior of bronchopulmonary neuroendocrine tumors (bNET) associated with multiple endocrine neoplasia type 1 (MEN1) are not well defined. This study aimed to determine the prevalence, potential precursor lesions and prognosis of bNET in patients with MEN1. METHODS: A database of 75 prospectively collected MEN1 cases was retrospectively analyzed for bNET. Patient characteristics, imaging and treatment were evaluated. Resection specimens of operated patients were reassessed by two specialized pathologists. Available CT scans of the whole cohort were reviewed to determine the prevalence of bronchopulmonary nodules. RESULTS: Five of the 75 MEN1 patients (6.6%; 2 male, 3 female) developed histologically confirmed bNET after a median follow-up of 134 months. The median age at diagnosis of bNET was 47 years (range 31-67), and all patients were asymptomatic. Four patients underwent anatomic lung resections with lymphadenectomy; the remaining patient with multiple lesions had only a wedge resection of the largest bNET. Tumor sizes ranged from 7 to 32 mm in diameter, and all bNET were well differentiated. Two patients had lymph node metastases. Two of 4 reevaluated resection specimens revealed multifocal bNET, and 3 specimens showed tumorlets (up to 3) associated with multifocal areas of a neuroendocrine cell hyperplasia within the subsegmental bronchi. One bNET-related death (1.3%) occurred during long-term follow-up. Review of the available CT scans of the patients without proven bNET revealed small bronchopulmonary lesions (≥3 mm) in 16 of 53 cases (30.2%). CONCLUSIONS: bNET in MEN1 might be more common than previously recognized. Their natural course seems to be rather benign. Multifocal tumorlets and multifocal neuroendocrine cell hyperplasia might represent their precursor lesions.

Contrast-enhanced postmortem computed tomography in clinical pathology: enhanced value of 20 clinical autopsies.

Postmortem computed tomography (PMCT) is a modern tool that complements autopsy diagnostics. In clinical autopsies, a major cause of death is cardiovascular disease. To improve the performance of PMCT in cardiovascular disease, full body angiography was developed (PMCT angiography [PMCTA]). Twenty PMCTA scans generated before autopsy were compared with native PMCT and clinical autopsy. The objective of the study was to quantify the additional diagnostic value of adding angiography to native imaging and to compare PMCT and PMCTA findings to autopsy findings. The diagnosis of the cause of death was identical or overlapped in 80% of the cases that used PMCTA and 70% that used PMCT. The additional diagnostic yield given by PMCT and PMCTA in combination with autopsy was 55%. PMCT yielded additional diagnoses in the musculoskeletal system. The greatest additional diagnostic value of PMCTA was in association with cardiovascular diagnoses. The accuracy of PMCTA for cardiac causes of death was 80%, and the positive predictive value was 90%. The findings indicate that native PMCT cannot display the cardiovascular system sufficiently clearly for high-quality diagnostic assessment. However, PMCTA is a powerful tool in autopsy cases with a history of cardiovascular disease and/or a suspected cardiovascular cause of death. The combination of PMCTA and clinical autopsy enhances diagnostic quality and completeness of the autopsy report. Furthermore, in cases without consent or with a restricted consent for clinical autopsy, PMCTA has the potential to provide information on cardiovascular causes of death.