Carcinoid syndrome caused by a pulmonary carcinoid mimics intestinal manifestations of ulcerative colitis: A case report.

BACKGROUND: Pulmonary carcinoids are rare, low-grade malignant tumors characterized by neuroendocrine differentiation and relatively indolent clinical behavior. Most cases present as a slow-growing polypoidal mass in the major bronchi leading to hemoptysis and pulmonary infection due to blockage of the distal bronchi. Carcinoid syndrome is a paraneoplastic syndrome caused by the systemic release of vasoactive substances that presents in 5% of patients with neuroendocrine tumors. Due to such nonspecific presentation, most patients are misdiagnosed or diagnosed late and may receive several courses of antibiotics to treat recurrent pneumonia before the tumor is diagnosed. CASE SUMMARY: We report the case of a 48-year-old male who presented with cough, dyspnea, a history of recurrent pneumonitis, and therapy-refractory ulcerative colitis that completely subsided after the resection of a pulmonary carcinoid. CONCLUSION: We report and emphasize pulmonary carcinoid as a differential diagnosis in patients with nonresponding inflammatory bowel diseases and recurrent pneumonia.

Health care resource use and costs among patients with carcinoid syndrome in France: Analysis of the National Health Insurance Database.

OBJECTIVES: Carcinoid syndrome (CS) develops in approximately 20% of patients with neuroendocrine tumours (NET). This study described healthcare resource utilization and its associated costs among patients with NET and CS, using the French national health care data system. METHODS: Patients were included if they had a hospital stay associated with the code E34.0 "CS" and at least one delivery of a somatostatin analogue (SSA) between 01/01/2012 and 31/12/2016. The end of the analysis was either 31/12/2017 or the date of death, whichever occurred first. Mean overall costs were described by item of expenditure and by periods. RESULTS: 646 patients were included: 64yo, 55% men, 64% and 15% had NET from the small-intestine or lung, respectively. Among them, 309 patients were incident and 271 died during the study period. Mean overall cost per person per month (PPPM) was €2,892: €3,273 for the first year following diagnosis, €2,574 in "middle-years" and €5,039 within the year preceding death. The two most costly expenditure items were drugs (€1,695 PPPM) and hospital stays (€870 PPPM). CONCLUSION: The first year following diagnosis and the year preceding death are the two periods representing the highest costs for CS care in France. Successful disease management may contribute to lower costs in the intermediate period.

Breakthrough Symptoms Remain an Unmet Need in Symptomatic Patients With Neuroendocrine Tumors and Carcinoid Syndrome.

OBJECTIVES: The aims of the study were to assess the effects of breakthrough carcinoid syndrome symptoms on well-being in neuroendocrine tumor (NET) patients insufficiently controlled on long-acting somatostatin analog (SSA) and to assess patient experience with treatment options, physician communication, and disease information sources. METHODS: This study surveyed US NET patients from 2 online communities, experiencing at least one symptom, by utilizing a 64-item questionnaire. RESULTS: One hundred patients participated: 73% female, 75% age 56 to 75 years, and 93% White. Primary tumor distribution was as follows: gastrointestinal NET (n = 55), pancreatic NET (n = 33), lung NET (n = 11), and other NET (n = 13). All patients were actively treated with one long-acting SSA and experiencing breakthrough symptoms: diarrhea, flushing, or other (13% experienced one, 30% two, 57% greater than two). More than one third of treated patients experienced carcinoid-related symptoms daily. Sixty percent of respondents reported not having short-acting "rescue" treatment available, impacting well-being though anxiety or depression (45%), trouble exercising (65%), sleeping (57%), employment (54%), and maintaining friendships (43%). CONCLUSIONS: Breakthrough symptoms remain an unmet need, even in treated patients with NETs. Though still relying on physicians, NET patients are now also using the Internet. Improved awareness of optimal SSA use may improve syndrome control.

Arterial function, biomarkers, carcinoid syndrome and carcinoid heart disease in patients with small intestinal neuroendocrine tumours.

PURPOSE: Carcinoid heart disease (CHD) is a life-threatening complication of carcinoid syndrome (CS) characterised by tricuspid regurgitation (TR). However, there is an unmet need for earlier diagnosis of CHD. We cross-sectionally assessed the prevalence and potential predictive or diagnostic markers for CS and CHD in a contemporary cohort of patients with small intestinal neuroendocrine tumours (SI-NETs). METHODS: Biochemical characteristics, hepatic tumour load, measures of arterial and endothelial function, atherosclerosis, and transthoracic echocardiography were analysed in a prospective cross-sectional setting. RESULTS: Among the 65 patients studied, 29 (45%) had CS (CS+ ), and 3 (5%) CHD. CS+ was characterised by significantly higher hepatic tumour load, S-5-HIAA and fP-CgA, higher frequency of diarrhoea and flushing, and more frequent PRRT compared to CS- (for all, P < 0.05). Central systolic, central mean, and central end-systolic blood pressures were significantly higher in CS+ than in CS- (for all, P < 0.05). Subjects with grades 2-4 TR had higher hepatic tumour burden, fP-CgA, and S-5-HIAA compared to those with grades 0-1 TR, but measures of vascular function did not differ. fP-CgA (P = 0.017) and S-5-HIAA (P = 0.019) but not proBNP increased significantly according to the severity of TR. CONCLUSION: Although CS is common, the prevalence of CHD was found to be lower in a contemporary cohort of SI-NET patients than previously anticipated. Measures of arterial or endothelial function or carotid atherosclerosis do not identify subjects with mild TR. Echocardiography remains the most sensitive means to diagnose CHD in CS patients with high tumour burden and elevated CgA and 5-HIAA.

Recent Advances in the Diagnosis and Management of Carcinoid Syndrome.

Carcinoid syndrome, a paraneoplastic condition linked with the release of multiple humoral factors, affects around 30-40% of patients with well-differentiated neuroendocrine tumours. Carcinoid syndrome has a major and unfavourable impact on patients' quality of life; it raises costs when compared to non-functioning neuroendocrine tumours; and it causes patients' lifestyles to alter, such as food, job, physical activity, and social life. Somatostatin analogues have been the first-line therapy for individuals with neuroendocrine tumours and carcinoid disease for decades. While these drugs give considerable relief from carcinoid syndrome symptoms, clinical progression is unavoidable, necessitating further research into newer treatment measures. Carcinoid tumours are sometimes difficult to diagnose because of their vague or nonspecific symptoms. There have been several advancements in all aspects of carcinoid syndrome, as well as novel therapeutics, in the previous few years. New epidemiological studies show that it is becoming more common; increasing insights into the pathogenesis of its various clinical manifestations and its natural history: definition of prognostic factors; new methods to verify its presence; the development of new drugs to treat its various manifestations, both initially and in somatostatin-refractory cases; and an increased understanding of the pathogenesis, natural history, and management of the disease. An all language literature search was conducted on MEDLINE, COCHRANE, EMBASE, and Google Scholar till November 2021. The following search strings and Medical Subject Headings (MeSH) terms were used: "Recent advances", "Carcinoid syndrome", "Neuroendocrine Neoplasms" and "Carcinoid heart disease". We comprehensively reviewed the literature on the pathogenesis, clinical features, and newer treatment modalities for Carcinoid Syndrome. Recent advancements in research and management have resulted from advances in our understanding of the aetiology of carcinoid syndrome. The development of molecular indicators of aggressiveness improved serum tumour markers, and the molecular aetiology of carcinoid heart disease are all possible because of advances in molecular biology. We conducted a comprehensive review to update knowledge regarding the pathophysiology, diagnostic protocols, and current and newer treatments for carcinoid syndrome, which presently requires a multidisciplinary approach, due to the complexity of the illness's aetiology, diagnosis, and therapy.

Clinical Features and Prognosis of Patients with Carcinoid Syndrome and Carcinoid Heart Disease: A Retrospective Multicentric Study of 276 Patients.

INTRODUCTION: Carcinoid syndrome is the most frequent functional syndrome of neuroendocrine neoplasia. It is characterized by flushing, diarrhea, wheezing, hypotension, and exanthema and may cause carcinoid heart disease. METHODS: We assessed clinical characteristics and prognosis of patients with carcinoid syndrome and carcinoid heart disease in 276 patients from 3 referral centers. RESULTS: Carcinoid syndrome patients had a mean age of 57 years (range 21-84) and a normal BMI of 24.9 (SD 4.5; range 13.8-39.6). Most primaries were of small bowel or unknown primaries with distant metastasis in 94.6%. Flushing was the most frequent symptom in 74.3% of patients, followed by diarrhea in 68.8%, and wheezing in 40.9%. Pain was described by 45.3%, weakness by 23.5%, and weight loss of >10% in 6 months by 30.1% of patients. Carcinoid heart disease was diagnosed in 37.3% of patients (n = 104) by echocardiography and involved predominantly in the tricuspid valve. Combinations with other valve defects were common. Somatostatin analogs were taken by 80.4% of patients and 17% needed additional loperamide/opium tincture. Surgery and peptide receptor radiotherapy were most frequent treatments. The median survival of patients with carcinoid syndrome after diagnosis was 9 years. Prognosis was significantly impaired by male sex and diagnosis of carcinoid heart disease but surprisingly significantly increased by the presence of symptoms flushing and weakness. DISCUSSION/CONCLUSION: Carcinoid syndrome is associated with extensive disease and primaries in small bowels or of unknown primary. Weight loss, weakness, and pain are frequent, and carcinoid heart disease is diagnosed in more than one-third of patients.

Percutaneous Image-Guided Core Needle Biopsy of Neuroendocrine Tumors: How Common Is Intraprocedural Carcinoid Crisis?

PURPOSE: To retrospectively evaluate the incidence of carcinoid crisis, other complications, and physiologic disturbances during percutaneous image-guided core needle biopsy of neuroendocrine tumors (NETs) in the lung and the liver. MATERIALS AND METHODS: Between January 2010 and January 2020, 106 computed tomography (CT) or ultrasound (US)-guided core needle biopsies of lung and liver NETs were performed in 95 consecutive adult patients. The mean age was 64 ± 13 years, and 48% were female. The small bowel was the most common primary site (33%, 31/95), and 32 (34%) patients had pre-existing symptoms of carcinoid syndrome. The mean tumor size was 3.2 ± 2.6 cm, and mean number of passes was 3.4 ± 1.6. A 17/18-gauge needle was used in 91% (96/106) of the biopsies. Thirteen (12%) patients received either outpatient or prophylactic octreotide. RESULTS: No patients experienced carcinoid crisis or needed octreotide, inotropes, vasopressors, or resuscitation. A single biopsy procedure (0.9%, 1/106) was complicated by bleeding that required angiographic hepatic artery embolization. Changes in pre-biopsy- versus post-biopsy systolic blood pressure and heart rate were -1.6 mm Hg (P = .390) and 0.6 beat/min (P = .431), respectively. Tumor functional status, overall tumor burden, and the elevation of neuroendocrine markers were not associated with intraprocedural physiologic disturbances. There were 4 minor complications (0.4%, 4/106) associated with the biopsy procedure that were not attributed to hormone excretion from tumor manipulation. CONCLUSIONS: Percutaneous image-guided core biopsy of NETs is safe, with low complication rate and no definite carcinoid crisis in the current cohort.

Time to Sustained Improvement in Bowel Movement Frequency with Telotristat Ethyl: Analyses of Phase III Studies in Carcinoid Syndrome.

BACKGROUND: Telotristat ethyl is approved to treat carcinoid syndrome diarrhea in combination with somatostatin analogs. In TELESTAR and TELECAST phase III studies, patients with carcinoid syndrome received telotristat ethyl 250 or 500 mg 3 times per day (tid) or placebo tid in addition to somatostatin analogs. The aim of this prespecified analysis was to examine the time to reductions in bowel movements (BMs) in the TELESTAR and TELECAST studies using survival analysis methods. METHODS: First occurrence of sustained response was defined as the time to the first day of 2 consecutive weeks with a mean BM frequency improvement of ≥ 30% from baseline during the 12-week double-blind treatment periods. Time to first ≥ 30% worsening in BM frequency was also measured. Treatments were compared with the log-rank test; Cox regression models provided point and confidence interval estimates of the hazard ratios for each trial. RESULTS: In TELESTAR and TELECAST, majority of patients (69%) on telotristat ethyl experienced a sustained ≥ 30% improvement in BM frequency. The median time to sustained reduction of at least 30% in BM frequency was significantly faster (fewer days to onset) for telotristat ethyl compared with placebo in both TELESTAR (250 mg, HR = 2.3 [95% CI, 1.3-4.1, P = 0.004]; 500 mg, HR = 2.2 [95% CI, 1.2-3.9, P = 0.009]) and TELECAST (250 mg, HR = 3.9 [95% CI, 1.6-11.1, P = 0.003]; 500 mg, HR = 4.2 [95% CI, 1.7-11.7, P = 0.002]). In TELECAST, 42% of patients on placebo experienced sustained worsening in BM frequency compared with 20% on telotristat ethyl; no significant difference was observed in TELESTAR. CONCLUSION: The time of onset of sustained BM frequency improvement mean and range are important when considering use of telotristat ethyl in patients with carcinoid syndrome diarrhea. Telotristat ethyl may also reduce sustained worsening in BM frequency. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT01677910, NCT02063659.

Development of the Functional Assessment of Cancer Therapy-Carcinoid Syndrome Symptom Index.

OBJECTIVE: To develop a symptom-focused index to evaluate representative symptoms, treatment side effects, and emotional and functional well-being of patients with carcinoid syndrome (CS). METHODS: The development of the Functional Assessment of Cancer Therapy-Carcinoid Syndrome Symptom Index (FACT-CSI) followed US Food and Drug Administration guidelines for the development of patient-reported outcome (PRO) measures and involved the following: (a) literature review; (b) interviews with 14 CS patients; (c) interviews with 9 clinicians; and (d) instrument development involving input from a range of PRO measure development and CS experts. The resulting draft instrument underwent cognitive interviews with 7 CS patients. RESULTS: Forty-six CS sources were reviewed. Analysis of patient interviews produced 23 patient-reported symptoms. The most frequently endorsed physical symptoms were flushing, diarrhea, abdominal pain, fatigue, and food sensitivity/triggers. Seven priority CS emotional and functional themes were also identified by patients. Expert interviews revealed 12 unique priority symptoms - the most common being diarrhea, flushing, wheezing, edema, abdominal pain/cramping, fatigue, and 8 emotional and functional concerns. Through an iterative process of team and clinical collaborator meetings, data review, item reduction and measure revision, 24 items were selected for the draft symptom index representing symptoms, emotional concerns, global assessment of treatment side effects, and functional well-being. Cognitive interview results demonstrated strong content validity, including positive endorsement of item clarity (>86% across items), symptom relevance (>70% for most items), and overall measure content (86%). CONCLUSIONS: The FACT-CSI is a content-relevant, symptom-focused index reflecting the highest priority and clinically relevant symptoms and concerns of people with CS.

Clinical Benefits of Telotristat Ethyl in Patients With Neuroendocrine Tumors and Low Bowel Movement Frequency: An Observational Patient-Reported Outcomes Study.

OBJECTIVES: We evaluated carcinoid syndrome (CS) symptoms and the real-world effectiveness of telotristat ethyl (TE) among patients with ≤3 bowel movements (BM) per day. METHODS: Patients with CS initiating TE between March and November 2017 could participate in a nurse support program collecting demographic and CS symptom data before TE initiation (baseline) and during ≥1 monthly follow-up within 3 months. Symptoms for patients averaging ≤3 BM/d at baseline were evaluated using pre/post-Student t tests. RESULTS: Sixty-eight patients reported ≤3 BM/d at baseline. Symptom burden was high and similar to participants with higher daily BM frequency. After 3 months of TE, most patients reported stable or improved symptoms with significant improvements in urgency (88%; mean [SD], -13.2 [32.2]), stool consistency (88%; -1.3 [2.0]), BMs per day (81%; -0.2 [1.2]), abdominal pain (86%; -13.7 [25.8]), nausea (85%; -30.9 [35.7]), and daily flushing episodes (83%; -1.7 [4.4]; all except BMs per day, P < 0.05). CONCLUSIONS: This analysis illustrates high CS symptom burden among patients with relatively low daily BM frequency. After initiating TE, patients reported significant improvements in urgency, stool consistency, abdominal pain, nausea, and flushing episodes. Clinicians and population health managers should consider CS symptom burden beyond daily BM frequency when evaluating treatment selection.

Serotonin pathway in carcinoid syndrome: Clinical, diagnostic, prognostic and therapeutic implications.

Carcinoid syndrome represents the most common functional syndrome that affects patients with neuroendocrine neoplasms. Its clinical presentation is really heterogeneous, ranging from mild and often misdiagnosed symptoms to severe manifestations, that significantly worsen the patient's quality of life, such as difficult-to-control diarrhoea and fibrotic complications. Serotonin pathway alteration plays a central role in the pathophysiology of carcinoid syndrome, accounting for most clinical manifestations and providing diagnostic tools. Serotonin pathway is complex, resulting in production of biologically active molecules such as serotonin and melatonin, as well as of different intermediate molecules and final metabolites. These activities require site- and tissue-specific catalytic enzymes. Variable expression and activities of these enzymes result in different clinical pictures, according to primary site of origin of the tumour. At the same time, the biochemical diagnosis of carcinoid syndrome could be difficult even in case of typical symptoms. Therefore, the accuracy of the diagnostic methods of assessment should be improved, also attenuating the impact of confounding factors and maybe considering new serotonin precursors or metabolites as diagnostic markers. Finally, the prognostic role of serotonin markers has been only evaluated for its metabolite 5-hydroxyindole acetic acid but, due to heterogeneous and biased study designs, no definitive conclusions have been achieved. The most recent progress is represented by the new therapeutic agent telotristat, an inhibitor of the enzyme tryptophan hydroxylase, which blocks the conversion of tryptophan in 5-hydroxy-tryptophan. The present review investigates the clinical significance of serotonin pathway in carcinoid syndrome, considering its role in the pathogenesis, diagnosis, prognosis and therapy.

Management of Diarrhea in Patients With Carcinoid Syndrome.

Neuroendocrine tumors (NETs) arise from enterochromaffin cells found in neuroendocrine tissues, with most occurring in the gastrointestinal tract. The global incidence of NETs has increased in the past 15 years, likely due to better diagnostic methods. Small-bowel NETs are frequently associated with carcinoid syndrome (CS). Carcinoid syndrome diarrhea occurs in 80% of CS patients and poses a substantial symptomatic and economic burden. Patients with CS diarrhea frequently suffer from diarrhea and flushing and report corresponding impairment in quality of life, requiring substantial changes in daily activities and lifestyle. Treatment paradigms range from surgical debulking to liver-directed therapies to treatment with somatostatin analogs, nonspecific anti-diarrheal agents, and a tryptophan hydroxylase inhibitor. Other causes of diarrhea, including steatorrhea, short bowel syndrome, and bile acid malabsorption, should be considered in NET patients with refractory diarrhea. More therapeutic options are needed for symptomatic management of patients with NETs, and better understanding of the pathophysiology can empower clinicians with improved patient care.

Carcinoid Syndrome: Updates and Review of Current Therapy.

OPINION STATEMENT: Carcinoid syndrome (CS) is a complex disorder caused by functional neuroendocrine tumors (NETs). This debilitating disease is characterized by hyper-secretion of biologically active substances eliciting major hormonal symptoms burden and fibrotic changes that are often challenging for management. There have been a number of insights that have substantially advanced treatments since the introduction of somatostatin analogs (SSAs). Second-line treatments are needed in a substantial proportion of patients with advanced disease that have uncontrolled hormone secretion on the highest labeled doses of SSAs. International guidelines suggest several available options including dose escalation of SSAs, interferon alpha, everolimus, radionuclide therapy, liver-directed therapies, and the novel tryptophan hydroxylase 1 inhibitor, telotristat ethyl. The clear preference of one second-line therapy over the other is not stated since their relative and long-term efficacy are largely unknown, and standardized approach of hormonal response assessment is lacking in the literature. In the clinical setting, the treatment of CS is guided in conjunction with patients' performance status, tumor origin, grade, stage, and growth rate, with regard to both anti-hormonal, as well as anti-proliferative effect. There is an unmet need for further well-designed randomized placebo-controlled and head-to-head studies that systematically assess CS symptom control and biochemical response following a specific intervention.

Generalized Cytokine Increase in the Setting of a Multisystem Clinical Disorder and Carcinoid Syndrome Associated with a Novel NLRP12 Variant.

BACKGROUND: Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are a group of cytoplasmic sensors that survey danger signals released by invading pathogens or damaged tissue. Mutations in the NLRP subfamily affect pro-inflammatory mediators and cause nonspecific systemic symptoms. AIMS: We sought to identify a potential genetic etiology of an inflammatory syndrome in a patient that presented with an atypical multisystem illness with carcinoid syndrome as well as atopic and autoimmune features. METHODS: Exome sequencing was performed using the Agilent SureSelect Clinical Research Exome XT kit on an Illumina HiSeq 2500. Longitudinal monitoring of pro-inflammatory cytokines was performed. RESULTS: We identified a novel variant (heterozygous c.536C > T [p.Thr179Ile]) in the NLRP12 gene in a 63-year-old woman and her daughter, who presented with an unusual clinical syndrome that differs from autoinflammatory disorders previously reported in association with the NLRP subfamily gene mutations. This NLRP12 variant was predicted to be pathogenic by functional analysis through Hidden Markov Models (FATHMM). Both the mother and the daughter had episodes of abdominal pain, fever, diarrhea, skin rash, hypothyroidism, and elevated urine 5-hydroxyindoleacetic acid (5-HIAA) levels. The proband also had elevated serum levels of pro-inflammatory (IL-1ß, IL-6, IL-12, and TNF-α), Th1 (IL-2, IFN-γ), and Th2 (IL-4, IL-5, IL-13) cytokines, but not of Th17 (IL-17) and IL-10. CONCLUSION: This report adds to the expanding spectrum of clinical manifestations attributed to the NLRP subfamily gene variants and suggests a role of NLRP12 in the regulation of multiple cytokines.

Real-world treatment patterns, resource use and costs of treating uncontrolled carcinoid syndrome and carcinoid heart disease: a retrospective Swedish study.

OBJECTIVES: To quantify healthcare resource use (HRU) and costs in relation to carcinoid syndrome (CS) and carcinoid heart disease (CHD) in a real-world setting, and to provide perspective on treatment patterns. MATERIALS AND METHODS: Patient data and HRU were collected retrospectively from three Swedish healthcare registers. Adult patients diagnosed with metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) grade 1 or 2 and CS who purchased somatostatin analogs (SSAs), and experienced controlled (defined by SSAs use) and uncontrolled (defined by SSAs dose escalation) CS for ≥8 months during the study period were included. Patients diagnosed with CHD from the date of the GEP-NET diagnosis were included in the CHD study group. RESULTS: Overall, total HRU cost increased with uncontrolled CS and CHD. Total resource cost was 15,500€/patient during controlled CS (8 months), rising to 21,700€/patient during uncontrolled CS (8 months), representing an increase of ∼40% (6200€/patient). Costs/patient were driven mainly by SSA use, tumor-related medical interventions and examinations. The total mean cost/year of disease was 1100€/patient without CHD, compared to 4600€/patient with CHD, a difference of 3500€/patient. Excluding SSA cost burden, the main drivers of increased cost in CHD patients were surgical interventions and echocardiography. CONCLUSIONS: This study provides a comprehensive overview of the treatment patterns and burden of uncontrolled CS symptoms and CHD using Swedish national register data. Increases in medical interventions and examinations HRU and increased SSA use suggest that SSA dose escalation alone may not effectively control the symptoms associated with uncontrolled CS, highlighting an unmet treatment need in this patient group.

An update of lanreotide acetate for treatment of adults with carcinoid syndrome.

Carcinoid tumors are rare and usually slow-growing. Some patients with advanced metastatic disease however can develop symptoms of carcinoid syndrome, which results in debilitating diarrhea and flushing. Many treatments including chemotherapy were tried unsuccessfully in the past to treat this syndrome. The symptoms of carcinoid syndrome are thought to be related to the ability of the tumors to produce serotonin. The discovery that the production of this hormone can be inhibited by somatostatin led to the development of somatostatin analogues octreotide and lanreotide, which differ from native somatostatin in that they have a longer half-life. These compounds have shown dramatic responses in symptom control and reduction of serotonin metabolites including urinary 5-hydroxyindoleacetic acid (5-HIAA) levels. This review researches the origins of carcinoid tumors, the development of lanreotide as a treatment and future directions for the treatment of carcinoid syndrome.

Partial hepatic resections for metastatic neuroendocrine tumors: perioperative outcomes.

STUDY OBJECTIVE: Partial hepatic resection reduces tumor burden in patients with metastatic neuroendocrine tumors, thereby improving quality and length of life. These procedures can be challenging as well as life-threatening. Our aim was to evaluate our patients' perioperative outcomes and propose a definition for an intraoperative carcinoid crisis relevant to this surgery, given its unique surgical considerations. DESIGN: Retrospective study. SETTING: Mayo Clinic, Rochester, Minnesota. PATIENTS: One hundred sixty-nine patients undergoing partial hepatic resection for metastatic neuroendocrine tumors between 1997 and 2015 were identified retrospectively from a surgical database at Mayo Clinic Rochester. INTERVENTIONS: None. MEASUREMENTS: Intraoperative carcinoid crisis for patients undergoing hepatic resection of neuroendocrine tumors was defined. Patients' medical records were reviewed and data were abstracted describing patient and procedural characteristics and perioperative outcomes. MAIN RESULTS: There were no documented cases of carcinoid crisis (0.0%, 95% C.I. 0.0% to 2.2%). One patient developed clinical findings of an emerging carcinoid crisis, but was successfully treated with doses of octreotide and findings resolved in <10 min. Prophylactically 500 µg octreotide was given subcutaneously in 77% (130/169) of patients preoperatively. CONCLUSIONS: There were no documented cases of carcinoid crisis (0.0%, 95% C.I. 0.0% to 2.2%). Adverse events were infrequent.

Carcinoid-syndrome: recent advances, current status and controversies.

PURPOSE OF REVIEW: To review recent advances and controversies in all aspects of carcinoid-syndrome. RECENT FINDINGS: Over the last few years there have been a number of advances in all aspects of carcinoid syndrome as well as new therapies. These include new studies on its epidemiology which demonstrate it is increasing in frequency; increasing insights into the pathogenesis of its various clinical manifestations and into its natural history: definition of prognostic factors; new methods to verify its presence; the development of new drugs to treat its various manifestations, both initially and in somatostatin-refractory cases; and an increased understanding of the pathogenesis, natural history and management of carcinoid heart disease. These advances have generated several controversies and these are also reviewed. SUMMARY: There have been numerous advances in all aspects of the carcinoid-syndrome, which is the most common functional syndrome neuroendocrine tumors produce. These advances are leading to new approaches to the management of these patients and in some cases to new controversies.