The role of N-terminal pro-brain natriuretic peptide, chromogranin A, and 5-hydroxyindoleacetic acid in screening for carcinoid heart disease.

Carcinoid heart disease (CHD) is a serious complication for patients with neuroendocrine tumors (NETs), and early detection is crucial. We aimed to investigate N-terminal pro-brain natriuretic peptide (NT-proBNP), chromogranin A (CgA), and plasma 5-hydroxyindoleacetic acid (P-5-HIAA) as a screening tool for detection of CHD. We prospectively included patients with disseminated small intestinal NETs (SI-NETs) and performed transthoracic echocardiography (TTE), questionnaires, and biochemical assessment of NT-proBNP, CgA, and P-5-HIAA. The presence and severity of CHD was assessed using a scoring system based on echocardiographic characteristics. A total of 93 patients were included in the final analysis. Fifteen (16%) were diagnosed with CHD. The median NT-proBNP (219 ng/L vs. 124 ng/L, p = .05), CgA (3930 pmol/L vs. 256 pmoL/L, p < .0001), and P-5-HIAA (1160 nmol/L vs. 210 nmoL/L, p < .0001) were significantly higher in patients with CHD compared to non-CHD patients. For NT-proBNP, the area under the receiver operating characteristic (AUROC) curve for detection of CHD was 0.67 (95% CI: 0.50-0.84), and at a 260 ng/L cutoff level, the sensitivity and specificity were 46% and 79%. For CgA, the AUROC was 0.91 (95% CI: 0.84-0.97), and at a cutoff level of 598 pmol/L, the sensitivity and specificity were 100% and 69%. For P-5-HIAA, the AUROC was 0.89 (95% CI: 0.80-0.98), and at a cutoff level of 752 nmol/L, the sensitivity and specificity were 92% and 85%. In conclusion, CgA and P-5-HIAA proved excellent markers of CHD while NT-proBNP lacked the required diagnostic accuracy to be used as a screening tool.

The Risk of Second Primary Colorectal Adenocarcinomas Is Not Increased among Patients with Gastroenteropancreatic Neuroendocrine Neoplasms: A Nationwide Population-Based Study.

BACKGROUND: Second primary colorectal adenocarcinomas (SPCA) may occur with a higher frequency in patients with gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). In a nationwide population-based study, we investigated the risk of SPCA in GEP-NEN patients and compared it to the general population. METHODS: Using the nationwide Danish registries, we identified 2,831 GEP-NEN patients (median age 63 years [IQR 50-73 years], 53% women) diagnosed in 1995-2010. We used Cox regression to compare the incidence of SPCA in GEP-NEN patients relative to a gender- and age-matched general population sample of 56,044 persons. RESULTS: We observed 20 SPCAs among the 2,831 GEP-NEN patients with a total time at risk of 14,003 years (incidence = 143 per 100,000 person-years) and 770 colorectal adenocarcinomas in the general population of 56,044 persons with a total time at risk of 466,801 years (incidence = 165 per 100,000 person-years). The hazard ratio (HR) of SPCA from GEP-NEN diagnosis to the end of follow-up was 1.22 (95% CI: 0.78-1.92) in GEP-NEN patients compared to the general population. This nonsignificant association was the result of a strong positive association in the first 6 months after diagnosis of GEP-NEN (HR = 9.43 [95% CI: 4.98-17.86]) followed by a negative association in the remainder of the follow-up period (HR = 0.50 [95% CI: 0.20-1.21]). CONCLUSION: In this population-based study, there was no increased risk of SPCA among GEP-NEN patients. The clinical workup in newly diagnosed GEP-NEN patients likely explains the positive short-term association followed by a negative association.