Carcinoid syndrome-Symptoms and therapeutic approaches.

The carcinoid syndrome (CS) is a constellation of symptoms attributed to hypersecretion of amines, prostaglandins and polypeptides. The cardinal symptoms of CS are flushing, diarrhea and bronchospasm; however, CS may present with various symptoms and signs, as: Skin: cutaneous flushes, cyanosis, pellagra, Gastrointestinal: diarrhea, nausea, abdominal cramps, vomiting, Heart: tricuspid and pulmonic valve thickening causing right heart failure, edema, Respiratory: wheezing, dyspnea.

Cases in a series of carcinoid syndrome and carcinoid heart disease.

Although carcinoid syndrome is regarded as a rare entity, carcinoid patients with evidence of cardiac involvement show a markedly reduced survival time. Patients with advanced signs of right-sided heart failure represent a subgroup at particularly high risk. Echocardiography remains the gold standard to diagnose or confirm structural cardiac involvement in patients with underlying carcinoid disease. This is the notion that propelled us to report on cases of carcinoid syndrome with cardiac involvement. We also review carcinoid syndrome and carcinoid heart disease, and challenges regarding the diagnosis and management of carcinoid heart disease.

Carcinoid syndrome: update on the pathophysiology and treatment.

Approximately 30-40% of patients with well-differentiated neuroendocrine tumors present with carcinoid syndrome, which is a paraneoplastic syndrome associated with the secretion of several humoral factors. Carcinoid syndrome significantly and negatively affects patients' quality of life; increases costs compared with the costs of nonfunctioning neuroendocrine tumors; and results in changes in patients' lifestyle, such as diet, work, physical activity and social life. For several decades, patients with neuroendocrine tumors and carcinoid syndrome have been treated with somatostatin analogues as the first-line treatment. While these agents provide significant relief from carcinoid syndrome symptoms, there is inevitable clinical progression, and new therapeutic interventions are needed. More than 40 substances have been identified as being potentially related to carcinoid syndrome; however, their individual contributions in triggering different carcinoid symptoms or complications, such as carcinoid heart disease, remain unclear. These substances include serotonin (5-HT), which appears to be the primary marker associated with the syndrome, as well as histamine, kallikrein, prostaglandins, and tachykinins. Given the complexity involving the origin, diagnosis and management of patients with carcinoid syndrome, we have undertaken a comprehensive review to update information about the pathophysiology, diagnostic tools and treatment sequence of this syndrome, which currently comprises a multidisciplinary approach.

Carcinoid syndrome: update on the pathophysiology and treatment

Approximately 30-40% of patients with well-differentiated neuroendocrine tumors present with carcinoid syndrome, which is a paraneoplastic syndrome associated with the secretion of several humoral factors. Carcinoid syndrome significantly and negatively affects patients' quality of life; increases costs compared with the costs of nonfunctioning neuroendocrine tumors; and results in changes in patients' lifestyle, such as diet, work, physical activity and social life. For several decades, patients with neuroendocrine tumors and carcinoid syndrome have been treated with somatostatin analogues as the first-line treatment. While these agents provide significant relief from carcinoid syndrome symptoms, there is inevitable clinical progression, and new therapeutic interventions are needed. More than 40 substances have been identified as being potentially related to carcinoid syndrome; however, their individual contributions in triggering different carcinoid symptoms or complications, such as carcinoid heart disease, remain unclear. These substances include serotonin (5-HT), which appears to be the primary marker associated with the syndrome, as well as histamine, kallikrein, prostaglandins, and tachykinins. Given the complexity involving the origin, diagnosis and management of patients with carcinoid syndrome, we have undertaken a comprehensive review to update information about the pathophysiology, diagnostic tools and treatment sequence of this syndrome, which currently comprises a multidisciplinary approach.

Transarterial Chemoembolization for Metastatic Neuroendocrine Tumors With Massive Hepatic Tumor Burden: Is the Benefit Worth the Risk?

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Primary neuroendocrine mediastinal tumor presenting with carcinoid syndrome and left supraclavicular lymphadenopathy: clinico-radiological and pathological features.

Primary mediastinal neuro-endocrine tumor is very rare. The primary modality to evaluate the lesion is computed tomography, to know disease extent, involvement of various structures, vascular invasion and metastasis. Histo-pathological and immuno-histochemical confirmation is mandatory. We report a rare case of primary neuroendocrine mediastinal tumor/atypical carcinoid in a young male who presented with carcinoid syndrome and left supraclavicular lymphadenopathy. Complete diagnostic work up was done followed by histo-pathological and immuno-histochemical confirmation. Later on patient underwent radical surgery followed by chemotherapy. The patient is currently on follow up. Neuroendocrine carcinoma of the thymus generally follows an aggressive clinical course.The biologic behavior is directly related to grade and degree of differentiation. This case report of primary low grade neuroendocrine tumor/atypical carcinoid adds to the biological behavior of this tumor and sheds light on the radiological and pathological features of neuroendocrine carcinomas.

Carcinoid syndrome diagnosed by echocardiography.

Right heart failure is a common presentation to both general physicians and cardiologists. Echocardiography is a useful investigation, and usually imaging of the liver is confined to helping estimate the right atrial pressure. We report a case of right heart failure where incidental imaging of the liver architecture during transoesophageal echocardiography helped in establishing the final diagnosis.

Comparison of prognostic value of tissue Doppler imaging in carcinoid heart disease versus the value in patients with the carcinoid syndrome but without carcinoid heart disease.

The aim of this study was to evaluate the prognostic value of tissue Doppler imaging (TDI) in carcinoid heart disease (CHD). We prospectively enrolled 56 consecutive patients with proved digestive endocrine tumor and carcinoid syndrome. All patients underwent serial conventional, contrast, and TDI echocardiographic studies. The end point was all-cause mortality. Mean follow-up was 34 +/- 21 months. At the end of follow-up, 30 patients (54%) presented right CHD and 13 patients (23%) left CHD. A progression of CHD was documented in 23 patients (41%). Twenty-two patients (39%) died during follow-up. According to mortality receiver operating characteristic curves, ratio of early transmitral flow velocity to early diastolic mitral annulus velocity (E/e' ratio) associated with an optimal sensitivity of 80% and specificity of 90% was 8. Mortality rate was significantly higher when the E/e' ratio was >or=8 (94% vs 10% when E/e' ratio was <8, p <0.0001). Using univariate analysis, the following factors were associated with death: left-sided CHD (p = 0.07) and E/e' ratio >or=8 (p <0.0001). The only independent marker of death detected by multivariate analysis was an E/e' ratio >or=8 (odds ratio 6.2, 95% confidence interval 1.95 to 19.7, p = 0.002). In conclusion, TDI used during routine transthoracic echocardiography can be helpful to identify high-risk patients with CHD.

Stenting of the superior mesenteric vein in midgut carcinoid disease with large mesenteric masses.

BACKGROUND: Midgut carcinoid (MGC) tumors generally develop in the small intestine and in >50% of cases also present with lymph node metastases in the mesentery. The majority of these tumors are surgically resectable, but a fraction are inoperable and may cause obstruction of the superior mesenteric vein (SMV), often associated with stasis of the intestinal wall and severe symptoms. These symptoms include severe abdominal pain, attacks of diarrhea, and malnutrition. METHODS: Seven patients with severe MGC including a large fibrotic inoperable mesenteric mass and severe symptoms were studied. After an obstructed SMV and signs of venous stasis in the small intestine were demonstrated, an expandable stent was inserted after puncturing an intrahepatic portal venous branch. The associated venography, patient symptoms, and radiological signs on computed tomography (CT) scans were evaluated. RESULTS: Four patients demonstrated resolution of their symptoms. In one patient who had intra-abdominal lymph leakage/chyloperitoneum, a complete normalization of the circulation followed and the intra-abdominal lymph leakage stalled. The venographies demonstrated normalization of the venous blood flow through the SMV, and CT scans demonstrated reduction in the thickness of the intestinal wall. In two cases there were no changes in the symptoms, and in one case a slight worsening of the symptoms ensued. In general, reductions of symptoms were associated with the degree of normalization of venous blood flow. CONCLUSIONS: We conclude that in selected patients with MGC stenting of the SMV may improve symptoms.

[Right ventricular failure as the presenting manifestation of a carcinoid syndrome]. / Atteinte cardiaque droite révélatrice d'un syndrome carcinoïde.

We report a 75-year-old woman with a severe and symptomatic valvular tricuspid dysfunction, revealing a carcinoid syndrome, confirmed by an octreotid scan and liver biopsy. Carcinoid heart disease is a common complication of carcinoid syndrome associated with poor prognosis. Despite new pharmacological treatment, valve replacement surgery is the only curative treatment. Early diagnosis and multidisciplinary management could improve prognosis and quality of life of these patients.

Benefits of routine use of coronal and sagittal reformations in multi-slice CT examination of the abdomen and pelvis.

AIM: To evaluate the usefulness of coronal and sagittal reformations from isotropic abdomino-pelvic computed tomography (CT) examinations. METHODS: Fifty consecutive abdomino-pelvic CT examinations were reconstructed into two sets of axial source images: 0.9 mm section width with 0.45 mm reconstruction interval (isotropic) and 4 mm section width with 3 mm reconstruction interval. The isotropic dataset was reformatted into coronal and sagittal stacks with 4 mm section widths. Three readers independently reviewed the three image sets with 4 mm section widths. The coronal and sagittal reformations were compared with the axial images, in the same sitting, for depiction of lesions in various abdominal organs. RESULTS: There was better visualization of lesions in the liver, kidneys, mesentery, lumbar spine, major abdominal vessels, urinary bladder, diaphragm and hips on the coronal reformations compared with source axial images (p<0.05). Sagittal reformations scored better than axial source images for showing lesions in the liver, thoracic spine, abdominal vessels, uterus, urinary bladder, diaphragm and hips (p<0.05). The coronal and sagittal series showed significant additional information in 23 and 17% of patients, respectively. CONCLUSION: Radiologists should consider the routine review of at least one additional plane to the axial series in the interpretation of abdomino-pelvic CT studies.

Carcinoid crisis after injection of 6-18F-fluorodihydroxyphenylalanine in a patient with metastatic carcinoid.

A carcinoid crisis is a severe complication of the carcinoid syndrome that can arise in patients with advanced metastatic neuroendocrine tumors. It can be initiated by stress, catecholamines, and tumor manipulation. In this article, we report a case in which an injection with the catecholamine tracer 6-18F-fluorodihydroxyphenylalanine, used for PET, induced a carcinoid crisis. Octreotide can be used for treatment and should be available. Tracer injection should be slow.

Factors associated with progression of carcinoid heart disease.

BACKGROUND: By releasing vasoactive substances into the circulation, carcinoid tumors can cause right-sided valvular heart disease. Factors associated with the progression of carcinoid heart disease are poorly understood. We conducted a retrospective study to identify such factors. METHODS: Our sample included 71 patients with the carcinoid syndrome who underwent serial echocardiographic studies performed more than one year apart and 32 patients referred directly for surgical intervention after an initial echocardiographic evaluation. A score for carcinoid heart disease was determined on the basis of an assessment of valvular anatomy and function and the function of the right ventricle. An increase of more than 25 percent in the score between studies was considered suggestive of disease progression. Tumor progression was assessed on the basis of abdominal computed tomographic scans and changes in the level of urinary 5-hydroxyindoleacetic acid (5-HIAA), a metabolite of serotonin. RESULTS: Of the patients with serial echocardiographic studies, 25 (35 percent) had an increase of more than 25 percent in the cardiac score. As compared with patients whose score changed by 25 percent or less, these patients had higher urinary peak 5-HIAA levels (median, 265 mg per 24 hours [interquartile range, 209 to 593] vs. 189 mg per 24 hours [interquartile range, 75 to 286]; P=0.004) and were more likely to have biochemical progression (10 of 25 patients vs. 9 of 46, P=0.05) and to have received chemotherapy (13 of 25 vs. 10 of 46, P=0.009). Logistic-regression analysis showed that a higher peak urinary 5-HIAA level and previous chemotherapy were predictors of an increase in the cardiac score that exceeded 25 percent (odds ratio for each increase in 5-HIAA of 25 mg per 24 hours, 1.08 [95 percent confidence interval, 1.03 to 1.13]; P=0.009); odds ratio associated with chemotherapy, 3.65 [95 percent confidence interval, 1.74 to 7.48]; P=0.001). CONCLUSIONS: Serotonin is related to the progression of carcinoid heart disease, and the risk of progressive heart disease is higher in patients who receive chemotherapy than in those who do not.