Carcinoid Research Articles

Clinico-Pathological Characteristics and Long-Term Outcomes of Incidental Appendiceal Carcinoid Tumors in Children

Background: Appendiceal carcinoid tumors are uncommon in children and are usually found incidentally during histopathological examination after appendectomy. Objectives: The aim of this study was to investigate the clinicopathologic characteristics and long-term outcomes of appendiceal carcinoid tumors in children. Methods: Patients under 18 years old with a diagnosis of appendiceal carcinoid tumor were analyzed. Demographical, clinical, radiological, surgical, and pathological data and long-term outcomes were evaluated. Results: A total of 10 (0.64%) appendiceal carcinoid tumors were found in 1562 appendectomy specimens. The mean age of children with appendiceal carcinoid tumors was 12.6 years, and the male-to-female ratio was 2:3. Tumor localization was at the tip of the appendix in 9 (90%) patients. Seven (70%) tumors were smaller than 1 cm, while 3 (30%) tumors were between 1 and 2 cm. The depth of tumor penetration reached the subserosa in 8 (80%) patients and the mesoappendix in the remaining 2 (20%) cases. Surgical margins were intact in all patients, and no additional surgery was performed. The patients were followed up for an average of 42.4 months, and no recurrence was detected. Conclusions: Appendiceal carcinoid tumors usually have nonspecific clinical-radiological findings and are almost always detected incidentally during the histopathological analysis of appendectomy specimens resected due to acute appendicitis. According to histopathology results, close follow-up and advanced surgical and medical treatments should be considered when necessary. Although the survival of patients is good, the possibility of colorectal malignancies should not be overlooked during follow-up.

Smart dual imprinted Origami 3D-ePAD for selective and simultaneous analysis of vanillylmandelic acid and 5-hydroxyindole-3-acetic acid carcinoid cancer biomarkers using graphene quantum dots coated with dual molecularly imprinted polymers

Measuring the levels of the biomarkers vanillylmandelic acid (VMA) and 5-Hydroxyindole-3-acetic acid (5-HIAA) is a valuable tool for clinical diagnosis not only of neuroblastoma or carcinoid syndrome, but also of essential hypertension, depression, migraine, and Tourette's syndrome. Herein, we explore using graphene quantum dots (GQDs) coated with molecularly imprinted polymer (MIP) as novel dual-imprinted sensors for selective and simultaneous determination of VMA and 5-HIAA in urine and plasma samples. The dual-MIP was successfully coated on the GQDs core via co-polymerization of (3-aminopropyl) triethoxysilane (APTES) and tetraethyl orthosilicate (TEOS), acting as functional and cross-linking monomers, respectively. In addition, we successfully created the dual imprinted VMA and 5-HIAA shell on the GQDs' core via a one-pot synthesis. We fabricated a facile and ready-to-use Origami three-dimensional electrochemical paper-based analytical device (Origami 3D-ePAD) for simultaneous determination of VMA and 5-HIAA using a GQDs@dual-MIP modified graphene electrode (GQDs@dual-MIP/SPGE). The Origami 3D-ePAD was designed to form a voltammetric cell on a three-layer foldable sheet with several advantages. For example, they were quickly assembled and enhanced the device's physical durability with the hydrophobic backup sheet. The developed dual imprinted Origami 3D-ePAD leads to substantially enhanced sensitivity and selectivity to electrochemical signal amplification generated from increasing the electrode-specific surface area, electrocatalytic activity, and the large numbers of dual imprinted sites for VMA and 5-HIAA detection. The synthetic recognition sites are highly selective for 5-HIAA and VMA molecules with an imprinting factor of 8.46 and 7.10, respectively. Quantitative analysis relying on square wave voltammetry reveals excellent linear dynamic ranges of around 0.001–25 μM, with detection limits of 0.023 nM for 5-HIAA and 0.047 nM for VMA (3Sb, n = 3). The Origami 3D-ePAD provides high accuracy and precision (i.e., recovery values of 5-HIAA ranged from 82.98 to 98.40 %, and VMA ranged from 83.28 to 104.39 %), and RSD less than 4.37 %) in urine and plasma samples without any evidence of interference. Hence, it is well suited as a facile and ready-to-use disposable device for point-of-care testing. It is straightforward, cost-effective, reproducible, and stable. Furthermore, it allows for rapid analysis (analysis time ∼20s) useful in medical diagnosis and other relevant fields.

Coming Back to the Basics. Comment on Cangir et al. A CT-Based Radiomic Signature for the Differentiation of Pulmonary Hamartomas from Carcinoid Tumors. Diagnostics 2022, 12, 416

We read with great interest the article by Cangir et al., “A CT-Based Radiomic Signature for the Differentiation of Pulmonary Hamartomas from Carcinoid Tumors”, published on 5 February 2022 [...]

Reply to Perrella et al. Coming Back to the Basics. Comment on "Cangir et al. A CT-Based Radiomic Signature for the Differentiation of Pulmonary Hamartomas from Carcinoid Tumors. Diagnostics 2022, 12, 416".

We thank to Dr. Perrella and and his fellow authors for your kind letter and thoughtful comments [...].

Chemokine Receptor CXCR4 Radioligand Targeted Therapy Using 177Lutetium-pentixather for Pulmonary Neuroendocrine Cancers.

Intermediate to high-grade lung neuroendocrine tumors (NETs; i.e., atypical carcinoid tumors) and neuroendocrine carcinomas (NECs) are currently difficult to cure. These tumors were found to express the CXCR4 G-protein coupled receptor that can be targeted with radioligands. PCR and flow cytometric analysis of lung NET and NEC cell lines using an anti-CXCR4 antibody demonstrated that all cell lines tested expressed CXCR4. PET/CT imaging with 68Galium-pentixafor in mouse xenografts of NETs and NECs verified tumor targeting that was blocked by a CXCR4 agonist. Clonogenic survival analysis demonstrated a more than additive enhancement of killing when 1 μM auranofin (a thioredoxin reductase inhibitor) was used as a radiosensitizer in combination with 177Lu-pentixather (10 μCi). DMS273 small cell lung cancer xenografts in female nude mice treated with 25 μCi/g 177Lu-pentixather induced inhibition of tumor growth and resulted in an increase in overall survival without causing unacceptable normal tissue toxicities. Immunohistochemical staining of 95 retrospective human samples (containing 90 small cell lung carcinomas) demonstrated 84% CXCR4 positivity. In a multivariable analysis of this cohort that included age, gender, stage, primary site, SSTR2 status, and CXCR4 status, Cox regression models determined that only distant metastasis at presentation (P < 0.01) and a CXCR4 H-score >30 (P = 0.04) were significantly associated with reduced survival. Prospective clinical testing of patient tumors identified CXCR4-positivity in 76% of 21 NECs, 67% of 15 lung NETs (including 8 of 10 atypical carcinoids), and 0% of 25 non-lung NETs (including 5 NETS G3s). These data support the hypothesis that CXCR4-targeted theranostics can be utilized effectively for select NETs and NECs.

Carcinoid tumor of the appendix with clinical picture of acute appendicitis, urgently operated on by laparoscopic appendectomy. Presentation of clinical case

Carcinoid tumor of the appendix with clinical picture of acute appendicitis, urgently operated on by laparoscopic appendectomy. Presentation of clinical case

Complete Regression of Endobronchial Carcinoid Tumor after an Endoscopic Biopsy.

An 80-year-old woman who had been diagnosed with an endobronchial carcinoid tumor visited our hospital for treatment with an endoscopic technique. However, a bronchoscopic examination at our hospital showed spontaneous regression of the tumor at the orifice of the right middle lobar bronchus. Chest computed tomography five months later revealed no local recurrence. This is the second report of an endobronchial carcinoid tumor vanishing after an endoscopic biopsy.

Maintaining quality of life after major lung resection for carcinoid tumor

BackgroundPulmonary carcinoid is a rare diagnosis with surgery remaining the standard treatment of choice. However, resection may impact patients’ daily activities due to decreased lung volume reserve and postoperative pain. Our study aims to compare the impact of different types of surgical resection on the post-operative quality of life with the application of a strict peri-operative pulmonary care program.MethodsPatients who underwent surgery for bronchopulmonary carcinoid tumors in a tertiary cancer center between August, 2017 and March, 2020 were identified and demographic data was collected. Patients were contacted via phone for the qualitative and quantitative assessment of pain and quality of life, utilizing the Arabic version of Short-form McGill Pain Questionnaire and Activity of Daily Living (ADL) instrument respectively. Lung reserve was assessed before and after surgery. Statistical analysis used Chi-Square for categorical variables and ANOVA for continuous variables.ResultsA total of 16 patients underwent different type of resection. The majority were male (n = 10; 63%) with a mean age of 44 years (19–81). Most common clinical stage was stage I (n = 12, 75%) with typical carcinoid features recorded in more than half of the cases (n = 11, 69%). Almost all patients underwent surgical excision (n = 15, 94%) with negative resection margin and no major post-operative complications. Bilobectomy was the most frequent procedure (n = 6, 40%) and video-assisted thoracoscopic surgery (VATS) was utilized in 8 patients (50%). Expected changes were recorded in pre- and postoperative pulmonary function test with an average drop of 10 in FEV1 and 14 mL/min/mmHg in DLCO. The majority of patients (n = 15, 94%) were totally independent doing daily activities. Mild intermittent pain was found in 7 patients (44%) who scored an average intensity of 1.6 out of 10.ConclusionsExcellent long-term outcomes can be achieved following surgical resection of pulmonary carcinoid tumors with little to no effect on patients’ lung function and quality of life in regard to performance status and post-operative pain when a good peri-operative pulmonary, physical rehabilitation, and pain management programs are adopted and strictly implemented.

Case series of ovarian neuroendocrine carcinoma: overview of clinicopathological features

BackgroundOvarian neuroendocrine carcinoma (O-NEC) is a relatively uncommon neoplasm, and the current knowledge regarding its diagnosis and management is limited. In this series, our objective was to provide an overview of the clinicopathological characteristics of the disease by analyzing clinical case data to establish a theoretical foundation for the diagnosis and management of O-NEC.Case presentationWe included three patients in the present case series, all of whom were diagnosed with primary O-NEC based on pathomorphological observation and immunohistochemistry. Patient 1 was a 62-year-old patient diagnosed with small cell carcinoma (SCC) of the pulmonary type. Post-surgery, the patient was diagnosed with stage II SCC of the ovary and underwent standardized chemotherapy; however, imaging examinations conducted at the 16-month follow-up revealed the existence of lymph node metastasis. Unfortunately, she passed away 21 months after the surgery. The other two patients were diagnosed with carcinoid tumors, one at age 39 and the other at age 71. Post-surgery, patient 2 was diagnosed with a carcinoid in the left ovary, whereas patient 3 was diagnosed with a carcinoid in her right ovary based on clinical evaluation. Neither of the cases received adjuvant therapy following surgery; however, they have both survived for 9 and 10 years, respectively, as of date.ConclusionPrimary O-NECs are rare and of diverse histological types, each of which has its own unique biological features and prognosis. SCC is a neoplasm characterized by high malignancy and a poor prognosis, whereas carcinoid tumors are of lesser malignancy and have a more favorable prognosis.

Incidental Carcinoid Tumor of the Appendix After Appendectomy During Pregnancy

Incidental Carcinoid Tumor of the Appendix After Appendectomy During Pregnancy

Abstract 12851: Severe Right and Left-Sided Multi-Valvular Carcinoid Heart Disease Associated With Ovarian Carcinoid Tumor

Carcinoid tumors are neuroendocrine neoplasms that secrete vasoactive substances, primarily serotonin, and have an incidence of approximately 2 in 100,000 people. Up to 60% of carcinoid tumors result in carcinoid heart disease (CHD), and unlike other carcinoid tumors, ovarian carcinoid tumors can involve the heart without liver metastasis. By bypassing the liver, ovarian carcinoid tumors can result in CHD in the absence of liver metastasis. We present a rare case of a 40-year-old female who presented in cardiogenic shock requiring inotropic support with echocardiographic evidence of preserved left ventricular systolic function (LVEF 50-55%) and multiple retracted leaflets that exhibited poor coaptation resulting in severe mitral regurgitation, torrential tricuspid regurgitation, and moderate-to-severe aortic regurgitation. Her left heart catheterization revealed non-obstructive coronary artery disease. A non-contrast CT torso revealed an isolated large septated left ovarian cystic mass (7.1x5.2 x7.1cm) without any other mass or lesion. In the setting of an elevated CA-125 (536units/mL, normal 0-35units/mL) and 24-hour urinary 5-HIAA (12.1mg, normal 2-9mg) with a normal CEA, CHD was suspected as the most likely diagnosis given the isolated ovarian mass and severe valvular disease. She underwent triple valve surgery in which valvular pathology revealed myxoid degeneration. Her post-operative course was complicated by multi-organ failure requiring multiple inotropes and V-A ECMO shortly thereafter, but the patient unfortunately passed away. While there are a few documented cases of CHD from ovarian carcinoid (less than 0.5% of cases) and left-sided CHD (less than 10% of cases), this is the first documented case, to our knowledge, describing severe right and left-sided CHD associated with a suspected ovarian carcinoid tumor.

Abstract 18974: Transcatheter Tricuspid Valve Replacement in a Symptomatic Bioprosthetic Tricuspid Stenosis Patient With Carcinoid Heart Disease: A Case Report

Background: Patients with carcinoid heart disease are prone to the development of mild to severe tricuspid regurgitation with or without accompanying tricuspid stenosis. We present an interesting case of a patient with bioprosthetic tricuspid valve stenosis secondary to carcinoid heart disease undergoing transcatheter tricuspid valve replacement (TTVR). Case history: The patient is a 64-year-old female with metastatic carcinoid syndrome and subsequent tricuspid valve replacement with 25 mm Magna ease bovine pericardial valve. The surgery was complicated by carcinoid crisis, pneumothorax, and complete heart block. She presented with worsening shortness of breath with exertion. Echocardiography revealed severe tricuspid stenosis associated with a severely dilated right atrium, moderate pulmonary stenosis. Transesophageal echocardiography confirmed carcinoid degeneration of the bioprosthetic tricuspid valve. CT chest and abdomen with contrast showed consistent findings of severe tricuspid stenosis, metastatic carcinoid tumor with new foci in liver, lungs. Ischemic evaluation with angiography revealed normal coronaries. Decision making: The patient was evaluated by the heart team and was considered to be a prohibitive risk patient for redo surgery. We then evaluated her suitability for transcatheter valve replacement, and the patient was felt suitable for undergoing valve-in-valve transcatheter tricuspid valve replacement via the right internal jugular vein approach because of the coaxial alignment of the valve through this route. The patient successfully underwent this procedure with a 26 mm balloon-expandable valve without any complications and is currently in NYHA class I functional status. Conclusion: Carcinoid syndrome can affect bioprosthetic tricuspid valves and transcatheter valve replacement may be advantageous in replacing the affected bioprosthetic valves by reducing morbidity and mortality.

Fulminant hypercorticism due to ACTG producing pheochromocytoma

Endogenous hypercorticism (EH) is a severe symptom complex caused by hypercortisolemia; according to the etiology, ACTH-dependent and ACTH-independent variants are distinguished, which, according to the literature, occur in 70-80% and 20-30% of cases, respectively. A rare cause of ACTH-dependent endogenous hypercorticism is ACTH-ectopic syndrome (ACTH-ES) (about 15-20% of cases). ACTH-ES is a syndrome of adrenocorticotropic hormone (ACTH) hyperproduction by neuroendocrine tumors of extrahypophyseal origin. Various tumors can secrete ACTH: bronchopulmonary carcinoid, small cell lung cancer, less frequently, thymus carcinoid, islet cell tumors and pancreatic carcinoid, medullary thyroid cancer, carcinoid tumors of the intestine, ovaries, as well as pheochromocytoma (PCC).This publication presents a clinical case of rarely detected paraneoplastic ACTH production by pheochromocytoma. Thepatient had clinical manifestations of hypercorticism, therefore, she applied to the Russian National Research Center of Endocrinology of the Ministry of Health of Russia. During the examination Cushing's syndrome (CS) was confirmed, multispiral computed tomography (MSCT) of the abdominal cavity revealed a voluminous formation of the left adrenal gland. Additional examination recorded a multiple increase in urinary catecholamine levels. Subsequently, the patient underwent left-sided adrenalectomy. The diagnosis of pheochromocytoma was confirmed morphologically, immunohistochemical study demonstrated intensive expression of chromogranin A and ACTH by tumor cells.

Should sampling of three N2 stations be a quality metric for curative resection of stage I lung cancer?

ObjectiveIn 2022, the American College of Surgeons Commission on Cancer issued standard 5.8 quality metric for curative lung cancer resections requiring nodal resection from 3 N2 stations. In this report, we compare oncologic outcomes after resection of 3 N2 stations versus 2 N2 stations in stage I non–small cell lung cancer. MethodsA retrospective review from a single institution database was conducted from 2011 to 2020 to identify patients with clinical stage I non–small cell lung cancer. Patients with a history of lung cancer, carcinoid tumors, and ground-glass lesions less than 50% solid component were excluded. The primary outcome was overall survival. Secondary outcomes included disease-free survival, recurrence patterns, and nodal upstaging. ResultsA total of 581 patients were identified and divided into 2 groups based on the number of N2 stations examined: Group A had 2 N2 stations examined (364 patients), and group B had 3 or more N2 stations examined (217 patients). Baseline demographic and clinical characteristics were similar between groups. In group A, N1 and N2 positive nodal stations were present in 8.2% (30/364) and 5.2% (19/364) of patients versus 7.4% (16/217) and 5.5% (12/217), respectively, in group B. Five-year overall survival and disease-free survival were 89% and 74% in group A versus 88% and 78% in group B, respectively. Recurrence occurred in 56 patients (15.4%) in group A (6.6% local and 8.8% distant) and 29 patients (13.4%) in group B (5.1% local and 8.3% distant; P = .73). ConclusionsThere was no significant difference in oncological outcomes in stage I non–small cell lung cancer resections that included 2 N2 stations compared with at least 3 N2 stations examined.

Appendiceal carcinoid tumor presenting as perforated appendicitis in pediatric patients: A case series and review of the literature

Appendiceal carcinoid tumor presenting as perforated appendicitis in pediatric patients: A case series and review of the literature

A case of a giant mediastinal thymic atypical carcinoid tumor

A case of a giant mediastinal thymic atypical carcinoid tumor

Recovery of Tricuspid Valve Function After Resection of a Primary Ovarian Carcinoid Tumor.

Recovery of Tricuspid Valve Function After Resection of a Primary Ovarian Carcinoid Tumor.

Robotic left upper lobectomy with bronchoplasty in a 54-year-old female with a left mainstem bronchial carcinoid tumor.

Robotic left upper lobectomy with bronchoplasty in a 54-year-old female with a left mainstem bronchial carcinoid tumor.

Radiological–pathological correlation in diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH): imaging and histopathology

To review histologically confirmed diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) cases and carry out a detailed pathological-radiological correlation to see if computed tomography (CT) can be used to confidently identify DIPNECH. Twenty-three histologically confirmed DIPNECH patients in the shared database of two NHS Trusts were reviewed. CT images were reviewed by two independent radiologists, each of them with >10 years of experience in thoracic imaging. All histological specimens were reviewed by a single pathologist with >25 years of experience. The diagnosis of DIPNECH was made according to the current World Health Organization (WHO) definition included in the WHO 2015 classification of pulmonary tumours. The results on histology were compared to the presence of nodules and air trapping on CT. Demographic information and, when available, molecular imaging studies and pulmonary function tests were also considered. There are prototypal clinical and radiological findings reflecting the presence of underlying histological DIPNECH: middle-aged women with multiple small and scattered nodules due to the clustering and proliferation of neuroendocrine cells. At least one larger, dominant, lung nodule reflecting a carcinoid tumour is very common and mosaic attenuation/air trapping is seen approximately in 50% of cases in inspiratory scans. Airflow obstruction is rarely associated with histological bronchial or peribronchial fibrosis, which suggests other mechanisms must be involved in its development. CT can be used to predict pathological DIPNECH in the appropriate clinical setting. It is important to consider DIPNECH to avoid overdiagnosis of more sinister conditions such as lung cancer or metastases.

The utility of fluorescence imaging in detecting primary and metastatic small bowel carcinoid tumors

BackgroundOur aim was to investigate utility of indocyanine green (ICG) and autofluorescence (AF) imaging in detection of small bowel primary and metastatic carcinoids. MethodsUsing Institutional Review Board approval, ICG and AF imaging of small bowel carcinoids was performed. Imaging findings were prospectively recorded in operating room and compared with conventional imaging, surgical exploration and pathologic findings. ResultsThere were 16 patients with 23 primary small bowel tumors, 27 mesenteric lymph nodes, 36 liver metastases and 2 peritoneal nodules. Carcinoid tumors exhibited brighter AF signals compared to background. AF imaging was superior to both DOTATATE PET and surgeon inspection/palpation in demonstrating small bowel primaries. Utility for metastatic lymph nodes and peritoneal metastases was limited. Superficial liver metastases exhibited brighter fluorescence compared to background on both ICG and AF imaging. ConclusionsThis is the largest study assessing utility of near-infrared fluorescence imaging in detection of small bowel carcinoids. Our results show promise in the utilization fluorescence imaging to detect occult primary tumors and superficial liver metastases.