pancreastatin and Malignant-Carcinoid-Syndrome

Neuroendocrine tumors (NETs) have a propensity to metastasize to the liver, often resulting in massive tumor burden and hepatic dysfunction. While transarterial chemoembolization (TACE) is effective in treating patients with NET metastatic to the liver, there are limited data on its utility and benefit in patients with large hepatic involvement. The aim of our study was to determine the clinical benefit and complication rate of TACE in patients with massive hepatic tumor burden.. Medical records were reviewed in patients with grade 1 or 2 NETs with hepatic metastasis at our institution from January 2000 to September 2014 who underwent TACE. Of 201 total patients, 68 had massive hepatic tumor burden involving >75 % of liver parenchyma.. Carcinoid syndrome was present in 40 (59 %) patients, and 57 (84 %) of the 68 patients were symptomatic from their disease. Complications beyond post-TACE syndrome occurred in 21.7 % of patients, with the most common complication being cardiac arrhythmias. The 30-day mortality rate was 7 %. Biochemical response was observed in 78 % of patients, while symptomatic relief and radiographic response was achieved in 85 and 82 % of patients, respectively. Median overall survival following TACE was 28 months, with 1-, 2-, and 5-year overall survival of 76, 54, and 26 %, respectively.. In spite of massive tumor burden, clinical and biochemical improvements were seen in the majority of patients. Morbidity was acceptable and reversible but with a fairly high mortality rate of 7 %. TACE should still be considered in selective patients with massive hepatic tumor burden from metastatic NET for symptom control and palliation.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Arrhythmias, Cardiac; Chemoembolization, Therapeutic; Chromogranin A; Female; Humans; Length of Stay; Liver Neoplasms; Male; Malignant Carcinoid Syndrome; Middle Aged; Patient Selection; Retrospective Studies; Risk Assessment; Survival Rate; Symptom Assessment; Treatment Outcome; Tumor Burden; Young Adult

Chromogranin A (CgA) is a useful marker of neuroendocrine tumors in humans. Here we describe and compare two immunoassay methods for determination of CgA, a radioimmunoassay (RIA) and an enzyme linked immunoassay (ELISA). The detection limit of the ELISA was lower than that of the RIA method (2 ng/ml versus 10 ng/ml, respectively), though the CgA RIA method covered a wider range than the CgA ELISA (10-920 ng/ml versus 2-500 ng/ml, respectively). There was no cross-reactivity with synthetic human and porcine pancreastatin (PST) in the two assays. There was a significant positive correlation between levels of CgA in sera from patients with carcinoid disease, measured by the two methods (r = 0.9, p < 0.0001), and the values were in the same range. Similarly, serum CgA levels in normal controls were also in the same range when assayed by the two methods. A commercially available porcine PST RIA method was evaluated, especially with respect to the influence of Sep-Pak extraction of serum on the levels of pancreastatin-like immunoreactivity (PST-LI). Ten sera from carcinoid patients were treated with Sep-Pak extraction, and levels of PST-LI were determined in non-extracted and extracted sera. There was a significant positive correlation between the concentrations of PST-LI measured in extracted and non-extracted carcinoid sera (r = 0.9, p < 0.002), and the levels were in the same range. There was also a significant positive correlation between levels of CgA and PST-LI in 49 carcinoid sera (r = 0.8, p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Antibody Specificity; Biomarkers, Tumor; Chromogranin A; Chromogranins; Cross Reactions; Enzyme-Linked Immunosorbent Assay; Humans; Malignant Carcinoid Syndrome; Nervous System Neoplasms; Neurosecretory Systems; Pancreatic Hormones; Radioimmunoassay; Swine

Pancreastatin-like immunoreactivity has been demonstrated in human carcinoid tumors by immunohistochemistry and radioimmunoassay, employing antisera raised to a synthetic C-terminal fragment of porcine pancreastatin. Immunohistochemistry revealed intense immunoreactivity in all tumors. By radioimmunoassay, high concentrations of pancreastatin-like immunoreactivity were measured in carcinoid tumors arising from the fore-gut (mean +/- S.D. and range: 369 +/- 955 and 9.4-3670 pmol g-1, respectively, n = 14), mid-gut (mean +/- S.D. and range: 1354 +/- 1538 and 337-3978 pmol g-1, respectively, n = 5) and in metastases associated with mid-gut tumors (mean +/- S.D. and range: 684 +/- 739 and 31-2255 pmol g-1, respectively, n = 7), compared to corresponding normal tissues (less than 1.4 pmol g-1). Individuals with hepatic metastases and carcinoid syndrome had elevated circulating levels of pancreastatin-like immunoreactivity (mean +/- S.D. and range: 770 +/- 1249 and 42-4120 pmol l-1; n = 12), significantly above the normal, fasting range (mean +/- S.D. and range: 14.9 +/- 7.5 and 4-37.5 pmol l-1, respectively, n = 42). However, patients with non-metastatic carcinoid tumors (n = 4), who had been clinically cured after primary tumor resection, had plasma levels within the normal range. Chromatographic analysis of extracts of primary lung and ileal tumors, hepatic metastases from ileal tumors and plasma from individuals with carcinoid syndrome revealed molecular heterogeneity of pancreastatin-like immunoreactivity.

Topics: Adult; Aged; Amino Acid Sequence; Blotting, Western; Carcinoid Tumor; Chromatography, Gel; Chromatography, High Pressure Liquid; Chromogranin A; Female; Humans; Intestinal Neoplasms; Liver Neoplasms; Male; Malignant Carcinoid Syndrome; Middle Aged; Molecular Sequence Data; Pancreatic Hormones; Radioimmunoassay