Diagnosis Of Carcinoid Syndrome Research Articles

Gut microbial and functional alterations lead to metagenomic signatures for midgut neuroendocrine tumor patients and for carcinoid syndrome.

Midgut neuroendocrine tumors (NET) derive from enterochromaffin cells, which have an close interrelationship with intestinal microbiota. Recently, we utilized 16S rRNA sequencing to uncover that midgut NET patients have a depleted gut microbiome and a specific fecal microbial signature. This study aims to validate these findings and to further characterize the role of microbes and microbial metabolic pathways in midgut NET patients with and without carcinoid syndrome (CS). Fecal samples from 60 midgut NET patients and 20 household-matched controls were subjected to whole metagenomics sequencing. We found that the gut microbial community composition of midgut NET patients differed from that of controls, with 2 genera, 17 species and 9 microbial pathways showing differential abundance (p < 0.001). No differences in microbial composition were observed between midgut NET patients with and without CS (p < 0.05). However, we did observe changes in inter-genus correlations of Bacteroides, Odoribacter, Parasutterella, Klebsielle, Ruminococcus and Proteobacteria when comparing these two patient groups. A signature of 16 microbial species (area under the receiver operating characteristic curve (AUROC) 0.892) or 18 microbial pathways (AUROC 0.909) accurately predicted the presence of a midgut NET. Furthermore, a microbial signature consisting of 14 functional microbial pathways distinguished CS patients from non-CS patients (AUROC 0.807). This study confirms that the gut microbiome of midgut NET patients is altered at the metagenomic level, which is not related to the presence of CS. A fecal microbial signature could constitute a novel biomarker for the diagnosis of midgut NET or CS.

Biochemical factors in the blood serum of neuroendocrine tumor patients with carcinoid syndrome

Introduction. Carcinoid syndrome is the most common functional syndrome in patients with neuroendocrine tumors. More than 40 biochemical factors are responsible for the manifestation of carcinoid syndrome, among which serotonin is the most important. The study of biochemical markers of carcinoid syndrome and associated carcinoid heart disease is an important aim of laboratory examination in neuroendocrine tumors patients.Aim. Analysis of levels and diagnostic efficiency evaluation of chromogranin A (CgA), serotonin, pro-brain natriuretic peptide (proBNP) and platelet-derived growth factor (PDGF-BB) in the blood serum of neuroendocrine tumors patients with various clinical manifestations, including carcinoid syndrome and carcinoid heart disease.Materials and methods. 66 patients with neuroendocrine tumors of various localizations were examined (pancreas – 24 cases, small intestine – 21, large intestine – 6, lungs – 10, unkown primary focus – 5). 38 patients had liver metastases. In 43 patients, a clinic of carcinoid syndrome was observed, 16 had signs of carcinoid heart disease. The control group consisted of 30 practically healthy people. Serum levels of CgA, serotonin, and PDGF-BB were determined by enzyme immunoassay in microplate format: Chromogranin A NEOLISA (Eurodiagnostica, Sweden), Serotonin ELISA (IBL, German), and PDGF-BB ELISA Kit (Invitrogen, USA). The proBNP analysis was performed on a Cobas e601 automated analyzer (Roche, Switzerland).Results. In carcinoid syndrome, the medians of CgA, serotonin, and proBNP were the highest, differing statistically significantly from the control group. In patients with G3 tumors, the median PDGF-BB was statistically significantly higher than in controls, in contrast to G1 and G2. The highest diagnostic sensitivity in the general neuroendocrine tumors group was in CgA – 63.6 %, with a specificity of 100 %. In patients with carcinoid syndrome, the highest diagnostic sensitivity was characteristic of serotonin and chromogranin A (79 %), while in patients with CAD clinic, proBNP had the highest sensitivity – 93.8 %.Conclusion. The study revealed the high efficiency of СgA, with the highest sensitivity in common forms and tumors with high biological activity. Serotonin can be used in the diagnosis of carcinoid syndrome, associated with cardiofibrosis development. Pro-brain natriuretic peptide is a highly sensitive and specific marker of carcinoid heart disease. The highest levels of PDGF-BB are associated with a high grade of neuroendocrine tumors malignancy.

Neuroendocrine neoplasms of the small intestine and the appendix - update of the diagnostic and therapeutic guidelines (recommended by the Polish Network of Neuroendocrine Tumours) [Nowotwory neuroendokrynne jelita cienkiego i wyrostka robaczkowego - uaktualnione zasady diagnostyki i leczenia (rekomendowane przez Polską Sieć Guzów Neuroendokrynnych)

Updated Polish recommendations for the management of patients with neuroendocrine neoplasms (NENs) of the small intestine (SINENs) and of the appendix (ANENs) are presented here. The small intestine, and especially the ileum, is one of the most common locations for these neoplasms. Most of them are well-differentiated and slow-growing tumours; uncommonly - neuroendocrine carcinomas. Their symptoms may be untypical and their diagnosis may be delayed or accidental. Najczęściej pierwszą manifestacją ANEN jest jego ostre zapalenie. Typical symptoms of carcinoid syndrome occur in approximately 20-30% of SINENs patients with distant metastases. In laboratory diagnostics the assessment of 5-hydroxyindoleacetic acid concentration is helpful in the diagnosis of carcinoid syndrome. The most commonly used imaging methods are ultrasound examination, computed tomography, magnetic resonance imaging, colonoscopy and somatostatin receptor imaging. Histopathological examination is crucial for the proper diagnosis and treatment of patients with SINENs and ANENs. The treatment of choice is a surgical procedure, either radical or palliative. Long-acting somatostatin analogues (SSAs) are essential in the medical treatment of functional and non-functional SINENs. In patients with SINENs, at the stage dissemination with progression during SSAs treatment, with high expression of somatostatin receptors, radioisotope therapy should be considered first followed by targeted therapies - everolimus. After the exhaustion of the above available therapies, chemotherapy may be considered in selected cases. Recommendations for patient monitoring are also presented.

European Neuroendocrine Tumor Society (ENETS) 2022 Guidance Paper for Carcinoid Syndrome and Carcinoid Heart Disease

European Neuroendocrine Tumor Society (<scp>ENETS</scp>) 2022 Guidance Paper for Carcinoid Syndrome and Carcinoid Heart Disease

In patients with well-differentiated neuroendocrine tumours, there is no apparent benefit of somatostatin analogues after disease control by peptide receptor radionuclide therapy.

Peptide receptor radionuclide therapy (PRRT) and somatostatin analogues (SSAs) are commonly combined as primary treatment for neuroendocrine neoplasms (NEN), and SSAs given as maintenance. We sought to evaluate whether sequential therapy with PRRT followed by SSAs has progression or survival benefits in patients with NEN after disease control by PRRT. This prospective, randomised, single-centre study had as principal eligibility criteria: unresectable, locally advanced, or metastatic, histologically confirmed well-differentiated NEN; no symptoms/biochemical diagnosis of carcinoid syndrome; no SSAs or ≤ 3months of SSAs before PRRT; and stable disease or partial or complete response after PRRT. Altogether, 115 patients were randomised 2:1 to an SSA group (n = 74) given octreotide acetate LAR every 4weeks, or a control group (n = 41) receiving only best supportive care. Octreotide treatment was to stop upon intolerable toxicity or patient refusal, or, at physician/patient discretion, upon NEN progression. The primary endpoint was progression-free survival (PFS), the secondary endpoint, and overall survival (OS). Median (25th-75th percentile) follow-up from the first PRRT activity to death or latest observation was 6.6 (3.18-10.22) years. During that time, 71/115 patients (62%) progressed, 52/74 (70%) in the SSA group, and 19/41 (46%) in the control group (p = 0.01). Eighty-eight/115 patients (76%) died, 58/74 (78%) in the SSA group, and 30/41 (73%) in the control group (p = 0.52). Median (95% CI) PFS was 4.7 (2.8-7.7) years in the SSA group, and 6.4 (4.1-not reached) years in controls. Overall, median OS was 6.6years. Neither PFS nor OS differed between groups (p = 0.129, p = 0.985, respectively). In patients with disease control after PRRT, subsequent SSA treatment appeared not to be associated with better PFS or OS. Whether to continue SSA administration upon progression after PRRT requires evaluation in a prospective, randomised, controlled multicentre study with a relatively homogeneous sample.

Carcinoid Syndrome: A Review.

Carcinoid syndrome (CS) is a paraneoplastic syndrome caused by the release of serotonin and other substances from well-differentiated neuroendocrine tumors (NETs). The hallmark symptoms of carcinoid syndrome are flushing and diarrhea; atypical signs and symptoms can include wheezing, abdominal pain, valvular heart disease, telangiectasias, pellagra, and the complications of mesenteric fibrosis, including ureteral obstruction, bowel obstruction, and bowel ischemia. These symptoms are mediated by the release of serotonin (5-HT), histamine, kallikrein, prostaglandins, and tachykinins. The diagnosis of CS requires these symptoms and corresponding elevations in lab tests. Treatment options include surgery and medical management with somatostatin analogs.

Burden of carcinoid heart disease in patients initiating treatment for carcinoid syndrome.

262 Background: Carcinoid heart disease (CaHD) develops as a complication of uncontrolled carcinoid syndrome (CS) due to overproduction of serotonin. Delayed diagnosis or control of CS may result in a greater prevalence of cardiac involvement. The objective of this study was to determine the burden of CaHD in patients initiating somatostatin analogs (SSA) for CS. Methods: This retrospective study investigated claims for commercially insured adults receiving SSA for CS between 2010 and 2016. Claims were evaluated for markers of CaHD such as tricuspid or pulmonary valve-related disease. Eligible patients had ≥ 1 medical claim for CS, had initiated SSA treatment, were continuously enrolled in their health plan for 30 days prior to SSA initiation and for ≥ 1 year, had no sign of acromegaly, and did not participate in a clinical trial during the study period. Patients were followed as long as they were observed in the dataset. Descriptive statistics examined demographic and treatment characteristics and costs for patients with (cases) and without (controls) a marker for CaHD during the study period. Results: A total of 654 patients with CS met the study criteria, of which 38% (n = 248) already had ≥ 1 marker for CaHD prior to initiating SSA treatment. At least 1 CaHD marker was identified in 46% (n = 185) of patients (cases) during the follow-up period. Except for age, all demographic characteristics were similar between cases and controls (n = 221). Cases were significantly older than controls (mean 67 vs. 64 years, p = 0.004). Average follow-up was 26 months (SD 22.0) for cases and 35 months (SD 24.8) for controls. Average time to observation of first CaHD marker for cases was 16 months (SD 16.7) after SSA initiation; most (84%) had ≥ 2 CaHD markers. Markers of right heart involvement were present in 20% of cases, and aortic or mitral valve involvement in 15% and 24%, respectively. Annual per patient expenditures were significantly higher for cases versus controls (mean [SD]: $51,825 [$70,423] vs $29,068 [$56,454], respectively). Conclusions: This study revealed that CaHD is common among patients with CS both before and after initiating SSA treatment. Early diagnosis and control of CS is necessary to reduce the burden of CaHD.

Pułapki w diagnostyce zespołu rakowiaka

Pułapki w diagnostyce zespołu rakowiaka

Carcinoid heart disease: typical fi ndings on echocardiography and cardiac magnetic resonance

Summary Carcinoid syndrome is often complicated by carcinoid heart disease. Deposition of carcinoid plaques on the endocardium of the tricuspid and pulmonary valves causes the typical echocardiographic iconography with thickening of the leafl ets and valvular insuffi ciency and/or stenosis leading to right heart failure. Additionally, the fi brous plaques can be visualized with cardiac magnetic resonance using delayed enhancement sequences. Accurate assessment of the dimensions of the dilated right ventricle by magnetic resonance implicates therapeutic options and defi nes prognosis. We report the case of a patient with advanced right heart failure as the clue to the diagnosis of carcinoid syndrome. Echocardiography was suggestive. Advanced investigation with magnetic resonance confi rmed carcinoid plaque deposition on the tricuspid and the pulmonary valves, and we also had evidence of plaque deposition in the right ventricle. Multimodality imaging is essential in the investigation of this rare disorder.

Growth of a solitary pulmonary nodule after 6 years diagnosed as oncocytic carcinoid tumour with a high 18‐fluorodeoxyglucose (18F‐FDG) uptake in positron emission tomography‐computed tomography (PET‐CT)

Pulmonary carcinoid tumour is low-grade neuroendocrine malignancy that is seen 1%-2% of all lung neoplasms. Oncocytic carcinoid type is a rarely seen variant of pulmonary carcinoids. As carcinoid tumours have hypometabolic activity, they usually have lower 18-fluorodeoxyglucose (18F-FDG) uptake than expected for lung carcinoma on positron emission tomography (PET). A 45-year-old non-smoking man had a stable solitary pulmonary nodule followed for 6years; the tumour remained the same size (1.5×2.4cm) during this period. The patient was admitted to the hospital with complaints of repetitive sneezing and rhinorrhoea. He also experienced flushing and bronchospasm. His chest X-ray revealed a minimal increase in the size of the solitary pulmonary nodule (2.0×2.8cm). In PET-computed tomography (CT), the parenchymal nodule in the anterior segment of the right lung had a standard uptake value of 38.0mg/mL, which was interpreted as a malignant nodule. He underwent fibre-optic bronchoscopy, but cytology showed no evidence of malignancy. Right upper and middle bilobectomy was performed, and a pulmonary carcinoid tumour with an oncocytic subgroup was diagnosed. The diagnosis of carcinoid syndrome was further confirmed by an elevated 24-h urinary excretion of 5-hydroxyindoleacetic acid. We present a rare case of an oncocytic carcinoid tumour with an increase in the size of a solitary pulmonary nodule after 6years' follow-up. In addition, PET-CT showed a very high 18F-FDG uptake in this patient, which is an unexpected finding with a pulmonary carcinoid tumour.

163 Long-term follow-up of patients with the carcinoid syndrome

Carcinoid heart disease (CaHD) may occur in patients presenting with carcinoid tumor and carcinoid syndrome. Studies evaluating the echocardiographic follow-up of these patients remain rare. The aim of this prospective study was to assess the progression of CaHD. We studied 90 consecutive patients presenting with carcinoid tumor and carcinoid syndrome. All patients underwent annual transthoracic echocardiographic studies and biological carcinoid markers. We used a previous validated score of CaHD severity. At baseline, prevalence of right- and left-sided CaHD was 32% and 8%, respectively, whereas at the end of follow-up (mean FU: 38 months), this prevalence was respectively 52% and 20%. Correlations were strong between urinary 5-HIAA and CaHD score (r = 0.86, p < 0.0001). All patients with at least 3 years of carcinoid syndrome and increased level of urinary 5-HIAA presented with echocardiographic evidence of CaHD. Interestingly, after three years of echocardiographic follow-up of treated patients with carcinoid syndrome but without CaHD, no patients developed CaHD. Prevalence of CaHD remains high and increases during follow-up. Carcinoid heart disease progresses over time, highlighting the need for echocardiographic follow-up once the diagnosis of carcinoid syndrome is made. On the other hand, after three years of normal follow-up, treated patients don’t develop CaHD.

Bioprosthetic Pulmonary and Tricuspid Valve Replacement in Carcinoid Heart Disease From Ovarian Primary Cancer

Carcinoid tumors usually originate in the gastrointestinal tract, but in rare instances they may arise in other organs. A patient with severe tricuspid and pulmonary regurgitation because of carcinoid syndrome successfully underwent double valve replacement using bioprostheses. The patient was finally diagnosed with carcinoid heart disease from an isolated ovarian carcinoid cancer. The diagnosis of carcinoid syndrome should be recognized as an etiology in patients with organic tricuspid and pulmonary regurgitation without left valvular disease.

Carcinoid Heart Disease: Medical and Surgical Considerations

Carcinoid tumors are rare, arising in 1.2-2.1 per 100,000 people in the general population per year.1 In 20%-30% of patients, the initial presentation occurs as a result of peptide production, ie, carcinoid syndrome. The malignant carcinoid syndrome consists of flushing, gastrointestinal hypermotility (secretory diarrhea), bronchospasm, and carcinoid heart disease. The syndrome is caused by the release of the vasoactive substances 5-hydroxytryptamine (serotonin), 5-hydroxytryptophan, histamine, bradykinins, tachykinins, and prostaglandins. The diagnosis of carcinoid syndrome is usually suspected by clinical features and confirmed by elevation of the byproduct of serotonin metabolism, 5hydroxy indole acetic acid (5HIAA). The urinary 5-HIAA (24hour collection) is a specific and reproducible test that provides a reliable biological marker for the assessment of tumor activity and the response to intervention.2 Measurement of circulating plasma chromogranin A, a protein produced by neuroendocrine cells, has also become a useful marker for carcinoid tumor diagnosis and follow-up.3,4

Carcinoid apudoma arising in a glomus jugulare tumor: Review of endocrine activity in glomus jugulare tumors

Previous reports of endocrine activity of glomus jugulare tumors have been of pheochromocytomas but not carcinoid apudomas. This paper is to alert the otolaryngologist to the presence of carcinoid apudomas in glomus jugulare tumors. A patient with a long history of explosive diarrhea, facial flushing, and violent headaches, the symptom of carcinoid syndrome, was cured after removal of his large glomus jugulare tumor. The diagnosis of carcinoid syndrome is made with a good history and confirmed with a 24 hour urine collection for 5 Hydroxy indole acetic acid (5 Hiaa). a series of patients treated at the Johns Hopkins Hospital for glomus jugulare tumors is reviewed for the presence of endocrine activity and the literature on endocrine active glomus jugulare tumors is presented. Preoperative evaluation for the presence of both pheochromocytoma and carcinoid apudoma is recommended for all patients with glomus jugulare tumors.