The rising incidence of neuroendocrine tumors (NETs) and delayed motherhood raise concerns about pregnancy outcomes and management, yet data remain scarce. This national cohort study, conducted through the GTE and RENATEN-ENDOCAN networks, included 17 women with NETs who experienced 26 pregnancies, resulting in 27 births. Maternal and fetal outcomes were analyzed based on tumor status, presence of carcinoid syndrome, and treatments during pregnancy. Early postpartum tumor evolution was evaluated using mRECIST on CT scans at 1 and 6 months after delivery. Median maternal age at first pregnancy was 31. Among women with resected localized NETs, 71.4% remained in remission post-pregnancy, while 28.6% experienced recurrence. In metastatic NETs, disease remained stable in 50% of cases, with 21.4% showing progression. Most progression was observed on 1-month postpartum scans. No worsening of carcinoid syndrome symptoms occurred. The overall cesarean rate was 16.7%, increasing to 25% in those with carcinoid syndrome. Live birth rates were high: 94.4% under surveillance and 91% under somatostatin analog (SSA) therapy. Intrauterine growth restriction rate was higher in patients receiving SSA therapy, while birth weight and length were not affected. No developmental issues were observed by age 2. Pregnancy is generally safe and successful in women with NETs. No major safety concerns were observed with SSA; however, these findings should be interpreted cautiously given the small sample size. Their use should remain individualized within a multidisciplinary approach, with early postpartum tumor assessment to optimize fetal and maternal outcomes.

The Clinical Impact of Patent Foramen Ovale in Patients With Carcinoid Heart Disease.

26-CCC-19205-ACC CARCINOID SYNDROME BEYOND THE VALVES: INTRACARDIAC METASTASES WITH SEVERE TRICUSPID DISEASE

Pellagra may complicate functioning pulmonary atypical carcinoid and present as a subtle acral dermatosis rather than the classical photo-distributed rash. In neuroendocrine tumor patients with chronic diarrhea and new skin changes, clinicians should suspect niacin deficiency and consider empiric nicotinamide, even when niacin assays are unavailable.

Persistent facial flushing as a cutaneous manifestation of carcinoid syndrome.

There is debate regarding the optimal management of small-bowel neuroendocrine tumours (SBNETs), particularly concerning upfront resection in various clinical presentations. While symptom phenotypes are known to influence survival, their impact on technical surgical quality, especially in the emergency setting, remains poorly defined. This study evaluates whether symptom phenotype compromises the delivery of guideline-concordant surgical care. A retrospective analysis of 108 consecutive SBNET resections (2000-2023) at a specialized tertiary centre was performed. Patients were stratified into four phenotypes: obstructive/perforation (n = 54), carcinoid syndrome (22), asymptomatic/incidental (22), and other symptoms (9). Operative metrics, including lymph-node harvest (LNY) and margin status (R0/R1), were compared alongside overall survival (OS). Symptom phenotype was a predictor of operative urgency and approach. Obstructive cases required emergency surgery in 50% of instances compared to ≤ 11% in all other groups (p < 0.001). Synchronous liver metastases were most prevalent in the carcinoid syndrome phenotype (50%) and lowest in the asymptomatic group (5%) (p = 0.002). Despite these disparities in presentation and urgency, technical quality markers were uniform across all groups: median LNY ranged from 10 to 13 (p = 0.426), R1/R2 margin rates were statistically similar (p = 0.290), and median length of stay was 8 days for all cohorts (p = 0.311). Multivariable analysis identified the asymptomatic phenotype as independently protective for OS (HR 0.42, p = 0.032), while liver metastasis was the strongest adverse prognostic factor (HR 3.25, p < 0.001). Symptom phenotype dictates operative urgency and reflects disease burden but does not compromise the technical standards of surgery in a specialized unit. These findings suggest that high-quality, guideline-concordant lymphadenectomy is achievable even in emergency obstructive presentations, and correspondingly, access to specialized surgical oncology expertise may be sought even in obstructed patients to ensure technical quality is maintained.

Somatostatin analogs such as octreotide are frequently used in the prevention of carcinoid syndrome in the perioperative period following neuroendocrine tumor resection. This is the first reported case of ventricular asystole associated with postoperative intravenous octreotide infusion in a patient with previous congenital cardiac surgery. We present the case of a 62-year-old white British male patient with a history of previous congenital cardiac surgery who sustained multiple episodes of ventricular asystole and associated loss of cardiac output during octreotide infusion. Recurrent asystole ceased following discontinuation of the octreotide infusion. Physicians caring for patients receiving intravenous octreotide should be aware of the potential arrhythmogenic adverse effects. While specific risk factors for octreotide-associated arrhythmias are not generally understood, previous cardiac surgery could potentially be one of these. Risk stratification guidance regarding patient groups requiring heightened monitoring while receiving intravenous octreotide is required. Monitoring recommendations may involve invasive blood pressure monitoring and telemetry in these cases.

Carcinoid syndrome (CS), the most prevalent neuroendocrine tumor (NET)-related hormonal syndrome, is associated with impaired survival. However, the contribution of NET-specific death in patients with this syndrome is currently unknown. This study aimed to evaluate overall survival (OS), prognostic factors, and causes of death in patients with CS. We retrospectively included patients with CS treated between 1995 and 2021 at our ENETS Center of Excellence. We used Kaplan-Meier curves and log-rank tests to perform survival analyses, and a Cox proportional hazards model to calculate mortality hazard ratios (HRs). A total of 295 of 427 included patients with CS died during follow-up, and cause of death was recorded in 255 patients. In 231 (90.6%) patients, the cause of death was NET-specific. Median OS was 7.1 years, and 65.1% and 34.1% of CS patients were alive at 5 and 10 years, respectively. Multivariate analysis identified age (HR, 1.06; P<.001), WHO tumor grade 2 (HR, 2.11; P=.01), plasma chromogranin A (CgA) level of 200 to 940 µg/L (HR, 1.64; P=.04), CgA level >940 µg/L (HR, 3.18; P<.001), and primary lung NET (HR, 1.77; P=.008) as negative predictors of survival. The presence of carcinoid heart disease (HR, 1.01; P=.97) was not associated with OS in a multivariate model due to interaction with CgA levels. Patients with CS are likely to succumb to their disease, with >90% of mortality being NET-specific. Age, tumor grade, primary lung origin, and CgA levels were independent predictors of mortality. These findings indicate that there is an urgent need for advances in therapeutic options for patients with CS.

Small intestinal neuroendocrine tumour (siNET) has distinct features and disease course compared to other gastrointestinal neuroendocrine tumours. While they mostly present with subtle symptoms, they also can present acutely requiring emergency surgical intervention. We assessed the impact of surgical intervention timing on oncological outcomes of siNET. A retrospective observational single centre cohort study of all patients diagnosed with siNET, and received surgical intervention at a tertiary level hospital between 2008 and 2025. A total of 66 patients were diagnosed with SiNET. 22 patients were excluded due to incomplete data (9 patients) and not meeting the eligibility criteria (13 patients). Total of 44 patients met the inclusion criteria, with 30% underwent emergency resection (n = 13) and 70% underwent elective resection (n = 31). Small bowel obstruction represented the most common cause for emergency presentations (61%), while incidental radiological findings (39%) and carcinoid syndrome (35%) accounted for most elective presentations. Emergency cases were associated with the absence of pre-operative somatostatin receptor imaging, less findings of mesenteric mass (31% vs. 81%), more likelihood of post operative macroscopic residual disease (46% vs. 23%) and disease specific mortality (75% vs. 23%). However, there was no statistically significant difference between the two groups in primary and secondary oncological outcomes. There were no operative or in-hospital mortality in either group as well as no significant difference in complications rates between the groups. Although emergency surgery was associated with limited preoperative staging and higher proportion of R2 resections, no statistically significant differences in overall survival, recurrence-free survival, carcinoid symptom resolution or local complications were observed. However, these results need to be interpreted cautiously due to the small sample size of the study.

BackgroundCarcinoid syndrome from pulmonary carcinoids without hepatic metastases is rare and diagnostically challenging when biochemical markers are normal.Case PresentationA woman in her mid‐60 s presented with an incidental right adrenal mass during evaluation for dyspnea and elevated D‐dimer. She reported a 20‐year history of paroxysmal tachycardia and 5 years of episodic flushing, profuse sweating, exertional dyspnea, and fine tremors triggered by minimal physical activity. Imaging revealed a 3.6 cm lipid‐rich adrenal adenoma and an 8 × 10 mm left upper lobe pulmonary nodule. Comprehensive biochemical evaluation was normal: 24 h urinary 5‐hydroxyindoleacetic acid 6 mg/d (normal 0–15), chromogranin A 50 ng/mL (normal 0–187), plasma metanephrine 0.12 nmol/L (normal 0.00–0.49), and normetanephrine 0.68 nmol/L (normal 0.00–0.89), excluding pheochromocytoma. Fine needle aspiration of the left pulmonary nodule confirmed a typical carcinoid tumor. Left upper lobe trisegmentectomy revealed low‐grade neuroendocrine neoplasm (pT1b pN0) with minimal mitotic activity (<1 per 10 HPF) and no necrosis. Postoperative 68Ga‐DOTATATE PET/CT demonstrated a radiotracer‐avid suspicious right lower lobe nodule (SUVmax 2.8) without hepatic metastases. Surgery markedly improved carcinoid syndrome symptoms, with residual episodes responding to long‐acting octreotide 20–30 mg every 4 weeks.DiscussionThis case illustrates that pulmonary carcinoid tumors can present with carcinoid syndrome despite normal biochemical markers and the absence of hepatic metastases. The temporal improvement following resection and response to octreotide established the diagnosis when biochemical testing was uninformative.ConclusionClinicians should maintain high suspicion for pulmonary carcinoids in patients with unexplained paroxysmal symptoms, even with negative biochemical testing and absent metastatic disease.

Pancreatic exocrine insufficiency (PEI) is an under-recognised cause of chronic diarrhoea in patients with neuroendocrine tumours (NETs). If left untreated or undertreated, PEI can lead to complications such as oxalate nephropathy (ON), which may result in loss of kidney function and potentially limit oncologic treatment options, including peptide receptor radionuclide therapy (PRRT). We present a man in his late 60s with a small bowel NET who developed persistent, uncontrolled diarrhoea for several years. The diarrhoea was attributed to multiple factors, including secretory NET (ie, carcinoid syndrome), bile acid diarrhoea and PEI secondary to somatostatin analogue therapy. Due to financial constraints, the patient was unable to consistently take pancreatic enzyme replacement therapy (PERT). Years after the diagnosis of NET, the patient developed a new onset worsening of kidney function. Further work-up, including a kidney biopsy, confirmed ON, which significantly limited subsequent treatment options, including PRRT. Routine screening for PEI and early initiation of PERT should be considered in all NET patients with chronic diarrhoea to prevent ON and preserve future treatment options.

Flushing in Carcinoid Syndrome.

Abstract Introduction Neuroendrocine tumours are rare neoplasms most commonly arising from the gastrointestinal system. Half of affected patients develop carcinoid syndrome characterised by vasomotor symptoms. Of these, 50% will develop carcinoid heart disease, with major morbidity and mortality due to right heart abnormalities. These are caused by the paraneoplastic effects of secreted vasoactive substances which bind to cardiac valve receptors, inducing fibroblast activation, progressive tricuspid and pulmonary dysfunction, and right-sided heart failure. Gallium-68 Fibroblast Activation Protein Inhibitor ([68Ga]FAPI) binds to activated fibroblasts, the key effector cells of valvulopathy in carcinoid heart disease, providing a readout of fibroblast activity. We used [68Ga]FAPI to investigate activated fibroblasts in patients with carcinoid syndrome. Methods In this prospective observational cohort study, patients with a history of carcinoid syndrome with and without associated heart disease, and healthy control volunteers, underwent hybrid [68Ga]FAPI positron emission tomography and magnetic resonance imaging. [68Ga]FAPI uptake was quantitatively assessed, with the maximal standardised uptake value (SUVmax) recorded within the defined region of interest, and divided by the right atrial blood pool uptake to provide a target-to-background ratio (TBRmax). We investigated tricuspid valvular [68Ga]FAPI uptake in patients and its’ relationship with key markers of disease severity and outcomes. Results Seventeen patients with active carcinoid syndrome (68±10 years; 53% male) and 9 control volunteers (60±6 years, 56% male) were included. Three patients had a confirmed diagnosis of carcinoid heart disease based on echocardiography findings. Visual [68Ga]FAPI uptake was observed in the tricuspid valve of all 3 patients with carcinoid heart disease as well as 7 patients with no overt valvular disease on echocardiography (figure 1). Intensity of valvular (tricuspid) fibroblast activation was highest in those with carcinoid heart disease, but was also higher in patients with carcinoid syndrome without valvular disease compared to control volunteers (Figure 2a, TBRmax 1.97 ± 0.1 versus 1.65 ± 0.2 versus 1.50 ± 0.2 respectively, ANOVA p=0.02). There was no relationship between tricuspid [68Ga]FAPI uptake and N-terminal pro B-type natriuretic peptide (NT-proBNP) (r=0.345, p=0.248), but a strong correlation with urinary 5-hydroxyindoleacetic acid (5-HIAA) (Figure 2b, r=0.645, p=0.005) Conclusion In patients with carcinoid syndrome, we demonstrate for the first time that valvular fibroblast activity can be visualised and quantified using [68Ga]FAPI. Patients with and without overt tricuspid valve disease had increased [68Ga]FAPI uptake which correlated with disease severity. Further work is required to explore the clinical implications of these observations given the emergence of disease-modifying therapy that may attenuate carcinoid-associated heart disease.

623 Background: Somatostatin analogs (SSA) are the mainstay treatment for advanced giNETs. However, more needs to be understood about the interchangeability and efficacy of commercially available options in sequential use. This study aimed to assess the efficacy of the lanreotide (Lan)—octreotide (Octre) switch in patients with advanced giNETs who experienced no disease progression during octreotide therapy. Methods: This retrospective cohort study analyzed patients with advanced giNETs treated at a single Brazilian cancer center between 2009 and 2021. We included all patients who received octreotide without disease progression and subsequently switched to lanreotide, due to institutional changes in local guidelines. Endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). Results: Among 199 patients with advanced giNETs treated with SSA, 53 transitioned to lanreotide after octreotide and were evaluated. The median age was 54 years (range 21 - 83). The majority had midgut (N=32, 60.4%) or pancreatic (N=16, 30.2%) tumors, with Ki67 index ≤ 2% (N=28, 52.8%) or 3 - 20% (N=20, 37.7%). Carcinoid syndrome was present in 25 patients (47%). Thirty-three patients (62.3%) received octreotide 20 mg before transitioning, while 20 (37.7%) received octreotide 40 mg. The median duration of previous octreotide use before transitioning to lanreotide was 34 months. The ORR and DCR with lanreotide were 10.6% and 89.4%, respectively. With a median follow-up of 34 months, 17 patients experienced progression or death, and the median PFS was not reached. The three-year PFS was 67.2% (95% CI 52.6% - 78.2%). PFS was not affected by previous octreotide dosage (40 mg vs 20 mg: HR 0.63, 95% CI 0.22 - 1.81, P=0.400) or duration (&gt; 36 vs ≤ 36 months: HR 1.44, 95% CI 0.53 - 3.88, P=0.464). With 14 deaths during the follow-up period, the three-year OS was 72.4% (95% CI 57.7% - 82.7%). Conclusions: Our data suggest that switching to lanreotide after octreotide in giNETs without progression maintains the efficacy of SSA, regardless of previous octreotide dosage or duration.

Adrenaline (epinephrine) is an endogenous catecholamine with potent β₁-adrenergic, moderate β₂-, and α₁-adrenergic activity, widely used in resuscitation and critical care. At lower infusion rates, it increases cardiac output and decreases systemic vascular resistance. While at higher doses it will result in greater inotropy and peripheral vasoconstriction, with potential adverse effects such as arrhythmias, lactic acidosis, and ischemia. This review synthesises contemporary evidence surrounding adrenaline's physiological and pharmacological profile, highlighting its role in cardiac arrest, perioperative medicine, sepsis, toxidromes, and specific contraindicated states. Clinical trials, including PARAMEDIC-2 and various observational registries, support adrenaline's effectiveness in achieving return of spontaneous circulation but raise concerns regarding neurological outcomes. The timing and dosing of adrenaline administration, particularly in non-shockable rhythms and in-hospital cardiac arrests, appear critical to optimising survival. Specific scenarios, such as post-cardiac surgery, neurosurgery, tamponade, and paediatric sepsis, demand tailored approaches due to distinct haemodynamic and pharmacological considerations. Conversely, adrenaline use may be contraindicated or require modification in patients with hypertrophic cardiomyopathies, carcinoid syndrome, or catecholamine-sensitive conditions. Despite its ubiquitous role in acute care, ongoing research is needed to define optimal dosing strategies and identify patient subgroups most likely to benefit from its use. Thoughtful, context-specific administration of adrenaline is essential to balancing efficacy with risk across the spectrum of emergency and perioperative medicine.

Neuroendocrine neoplasms have heterogeneous morphological features and varying clinical manifestations, which in turn influences their therapeutic approach. Histologically, based on cell morphology, they can be divided into neuroendocrine tumors and neuroendocrine carcinomas. Clinically, they are subdivided into functioning (in the presence of a specific tumor syndrome) and nonfunctioning (in cases where only general, nonspecific symptoms are observed). One of the most common clinical manifestations of functioning neuroendocrine tumors is carcinoid syndrome, caused by the tumor’s secretion of multiple hormonal amines and peptides, primarily serotonin. In most cases, these tumors are relatively indolent. However, as the disease slowly progresses, patients may experience delayed complications such as carcinoid heart disease, mesenteric fibrosis, malnutrition, and vitamin deficiencies. Carcinoid syndrome can also rapidly worsen to a life-threatening complication known as a carcinoid crisis. Given the multifaceted and insidious nature of carcinoid syndrome, effective treatment relies on the indispensable role of a multidisciplinary team consisting of gastroenterologists, endocrinologists, radiologists, oncologists, nuclear medicine physicians, surgeons, cardiologists, and nutritionists.

Paraneoplastic neurological syndromes (PNS) represent a rare but clinically significant group of disorders that arise as indirect effects of cancer through immune-mediated mechanisms. They differ from direct tumor invasion, metastasis, or treatment-related toxicity, and often precede cancer diagnosis, making early recognition essential. This review outlines the distinctions between carcinoid syndrome, paraneoplastic endocrine/metabolic syndromes, and PNS, highlighting their clinical relevance in oncology education. We summarize current knowledge on the pathophysiology, clinical spectrum, diagnostic approaches, and management strategies for PNS. Emphasis is placed on their educational value as models for interdisciplinary learning, diagnostic reasoning, and integration of oncology with neurology. Improved awareness among medical trainees and oncologists can enhance early detection, appropriate management, and patient outcomes.

Neuroendocrine neoplasms (NENs) originate mainly in the digestive system and lungs and are classified as neuroendocrine carcinomas (NECs) or neuroendocrine tumors (NETs). Breast metastases from NENs are rare, accounting for only 1% of breast neoplasms, but may be more frequent than expected. This study aimed to characterize patients with breast metastatic NENs through a literature review. A systematic review was conducted using PubMed, Embase, LILACS, and OpenGrey databases through July 2024. Eligible studies included case reports, case series, or cross-sectional studies documenting at least one breast metastatic NEN case confirmed by histopathology or imaging. Eighty-one articles with 138 cases were included. The mean age was 52.9 (SD 12.18) years, and three patients were male. NETs were more common than NECs (82.6 vs 14.5%), and the small intestine was the primary site in 45.3% of cases, followed by the lung (26.6%). Breast lesions were the first clinical manifestation in 24.8% of cases. Carcinoid syndrome symptoms occurred in 21.4% of patients. Ultrasonography revealed hypoechoic lesions with irregular margins, and mammography showed poorly defined margins. Chemotherapy was used in 57.4% of patients, typically with etoposide and platinum, and somatostatin analogs were administered to 36.2% of patients. Surgical resection of the primary tumor occurred in 74.6% of cases, and metastasis resection occurred in 73.5%. This review highlights the importance of accurate diagnosis, as a significant number of cases were initially misdiagnosed as primary breast tumors. Proper diagnostic evaluation can improve patient outcomes.

ObjectiveTo assess the prevalence, pre-procedure biomarkers, and management of carcinoid crisis (CC) in a cancer-specific hospital.DesignRetrospective observational study of subjects with carcinoid syndrome (CS) undergoing invasive procedures or systemic therapies over 5 years.MethodsElectronic haemodynamic parameters and patient records were extracted. CC incidence was assessed using strict (SBP <80 mmHg, >10 min) or broad criteria (severe hypotension, hypertension, arrhythmias, >1 min).Results48 patients with CS underwent 71 procedures (35 invasive procedures, 36 systemic therapies). CC did not occur during systemic therapies. Prophylactic octreotide infusion was used in 63% of invasive procedures. CC occurred in 43% of procedures as defined by broad criteria and in 20% as defined by strict criteria. Compared to those without CC, patients with strictly defined CC had higher chromogranin A (P < 0.001), higher 5-HIAA (P = 0.03), higher BNP (P = 0.03), longer hospital stay (P < 0.001), and higher postoperative complications (P < 0.001). Lower intraoperative mean arterial pressure (MAP) correlated with postoperative complications (ρ = −0.55, P = 0.004) and longer hospital stay (ρ = −0.62, P = 0.001). All subjects with strictly defined CC were treated with more than one drug; however, there were five patients with broadly defined CC who did not require treatment for transient haemodynamic instability.ConclusionsPre-operative biomarker assessment is essential to triage CS patients at risk of CC and thereafter trigger a risk-based management pathway. Prolonged intraoperative hypotension correlated best with postoperative outcomes, and is a better definition for CC in our cohort.

Abstract Background Neuroendocrine tumours (NETs) are uncommon cancers that can secrete vasoactive hormones, causing a range of symptoms. Approximately 50% of metastatic small bowel NETs develop carcinoid syndrome, with up to 50% historically developing carcinoid heart disease (CHD). With advances in medical therapy, contemporary characteristics and prognosis of CHD are unclear. Purpose To evaluate clinical characteristics, echocardiographic features, and outcomes of patients with NETs and CHD in a contemporary Canadian cohort and identify factors associated with CHD development and mortality. Methods This retrospective cohort study analyzed patients undergoing echocardiograms at a tertiary cancer centre-affiliated laboratory (2013-2023) with references to NETs or CHD in reports. Patients were classified based on whether they did or did not develop CHD in the study period. Baseline clinical characteristics, treatments, and outcomes were compared between the two groups. Baseline echocardiographic data (≤6 months from NET diagnosis) were reviewed to characterize features associated with CHD development. Interventions were compared between patients who survived &amp;lt;2.5 years after CHD diagnosis and those who survived ≥2.5 years or were alive by the end of the study period. Results In this 10-year period, 87 patients with NETs were identified [42 (48%) female; median age 61 (IQR 53-69) years] and 18 (21%) developed CHD [8 (44%) female; median age 66 (IQR 59-71) years]. Primary NETs of small bowel origin were more common in patients with CHD than those without CHD (83% vs. 55%, p=0.032). CHD patients exclusively had right-sided valve involvement: 100% tricuspid and 61% pulmonary; 2 (11%) had a patent foramen ovale. Compared to non-CHD patients at baseline echo, CHD patients demonstrated higher mean right atrial volume index (41mL/m2 vs 24mL/m2, p=0.001), higher mean right ventricular (RV) basal diameter (40mm vs. 34mm, p=0.006), and more frequent RV dysfunction (22% vs. 0%, p&amp;lt;0.001). Surgical valve replacement was performed in 9 (50%) CHD patients and was indicated but deferred in 6 (33%) due to competing comorbidities. The median survival of CHD patients was 2.4 vs. 13.4 years without CHD (p&amp;lt;0.001). NET progression and refractory heart failure were main reasons for mortality. Among CHD patients, primary NET resection was significantly associated with improved survival (p=0.009). Tyrosine kinase inhibitors and radiation therapy showed trends toward improved survival. Conclusions In our cohort of patients with NETs, CHD prevalence was lower than previously reported with all cases affecting only right-sided valves. Over half developed an indication for valve replacement though many were ineligible. Contemporary therapeutics, including medical and radiation therapies, showed trends toward improved survival. Further studies are needed to determine reasons behind differences in CHD prevalence, valvular involvement, and outcomes in the current era.Study design and findings Table 1.Clinical and echo data