Longitudinal Copy-Number Alteration Analysis in Plasma Cell-Free DNA of Neuroendocrine Neoplasms is a Novel Specific Biomarker for Diagnosis, Prognosis, and Follow-up.

PURPOSE: As noninvasive biomarkers are an important unmet need for neuroendocrine neoplasms (NEN), biomarker potential of genome-wide molecular profiling of plasma cell-free DNA (cfDNA) was prospectively studied in patients with NEN. EXPERIMENTAL DESIGN: Longitudinal plasma samples were collected from patients with well-differentiated, metastatic gastroenteropancreatic and lung NEN. cfDNA was subjected to shallow whole-genome sequencing to detect genome-wide copy-number alterations (CNA) and estimate circulating tumor DNA (ctDNA) fraction, and correlated to clinicopathologic and survival data. To differentiate pancreatic NENs (PNEN) from pancreatic adenocarcinomas (PAAD) using liquid biopsies, a classification model was trained using tissue-based CNAs and validated in cfDNA. RESULTS: One hundred and ninety-five cfDNA samples from 43 patients with NEN were compared with healthy control cfDNA (N = 100). Plasma samples from patients with PNEN (N = 21) were used for comparison with publicly available PNEN tissue (N = 98), PAAD tissue (N = 109), and PAAD cfDNA (N = 96). Thirty percent of the NEN cfDNA samples contained ctDNA and 44% of the patients had at least one ctDNA-positive (ctDNA+) sample. CNAs detected in cfDNA were highly specific for NENs and the classification model could distinguish PAAD and PNEN cfDNA samples with a sensitivity, specificity, and AUC of 62%, 86%, and 79%, respectively. ctDNA-positivity was associated with higher World Health Organization (WHO) grade, primary tumor location, and higher chromogranin A and neuron-specific enolase values. Overall survival was significantly worse for ctDNA+ patients and increased ctDNA fractions were associated with poorer progression-free survival. CONCLUSIONS: Sequential genome-wide profiling of plasma cfDNA is a novel, noninvasive biomarker with high specificity for diagnosis, prognosis, and follow-up in metastatic NENs.

Long-acting octreotide as secondary prevention of chemotherapy-induced diarrhea: proof of concept.

BACKGROUND: The aim of this study is to investigate the role of Octreotide LAR in secondary prevention in patients with chemotherapy-induced diarrhea. METHODS: In this study, patients experiencing CID ≥ grade 2 received 30 mg long-acting octreotide as a monthly injection and the next chemotherapy dose was administrated with a 25% dose decrease. If no CID ≥ grade 2 occurred, subsequent chemotherapy doses were increased to the initial 100% values. The primary endpoint of the study was the diarrhea control rate (< grade 2) for patients receiving the optimal dose of chemotherapy for a minimum of 2 cycles. RESULTS: Twenty-nine patients were included. Ten patients experienced no improvement or ended the study very early after the first injection of octreotide LAR. Nineteen patients had a reduction in the grade of diarrhea after the first administration of Octreotide LAR and a reduced chemotherapy dose. Seven of them (24%) did not reach the end of the study because of disease progression (6) or lost in follow-up (1). Ultimately 12 patients (41%) continued the study till the end. In ten of these twelve patients, there was a significant and persisting reduction of diarrhea while receiving full dose chemotherapy. CONCLUSION: This study suggests that monthly injections with long-acting octreotide might be used as a secondary prevention of chemotherapy-induced diarrhea. Its usefulness and optimal dosage in secondary prevention in combination with antidiarrheal agents needs further research.

Spontaneous dissection of the celiac trunk: a rare cause of abdominal pain--case report and review of the literature.

Spontaneous dissection of the celiac trunk is uncommon and rarely considered in patients presenting with acute onset of epigastric pain. We report the case of a 48-year old male, diagnosed with a spontaneous dissection of the celiac trunk extending towards the common hepatic artery. He was treated conservatively and remained asymptomatic after two years of follow-up. Conservative treatment seems justified in the absence of bowel ischemia or signs of hemorrhage. Initial Computed Tomography angiography revealed the presence of a dissection with a pseudoaneurysm that remained stable and regressed towards a normal Computed Tomography angiography after 7 months of follow-up. Radiologic follow-up is warranted as progression of the dissection and/or total occlusion with or without symptoms can occur. The risk factors, the natural course and optimal treatment remain unclear due to the rarity of the disorder. Our patient had no predisposing cardiovascular risk factors. Nevertheless, we observed a hypertrophic ligamentum arcuatum on Computed Tomography, possibly facilitating the evolution towards a dissection. Next to the case report, we provide a review of the available literature.