Carcinoid Research Articles

Omitting hemicolectomy for patients with appendiceal neuroendocrine tumours of 1–2 cm

Omitting hemicolectomy for patients with appendiceal neuroendocrine tumours of 1–2 cm

Atypical revelation of atypical lung carcinoid; back pain after SARS-COV2 vaccination: A case report

Background: Carcinoids make nearly 2% of all lung tumors, and the typical carcinoid are more frequent than atypical carcinoid (AC). Case presentation: We report a histologically confirmed AC case of a 23-years old male patient; revealed by back chest pain as the first presentation; after a covid vaccination. Past medical history revealed that the patient had received the covid-19 vaccine in the days before the presentation. Contrast-enhanced computed tomography scan of the thorax revealed a tumor mass of the right fowler. Conclusion: To our knowledge; this is the first case in literature. Whether bronchial carcinoid tumors are infrequent; they should be considered as differential diagnosis in patients even younger, with recurrent respiratory symptoms as timely and quick diagnosis is essential for curative intervention. We reported a first a COVID-19 vaccine- revealing symptoms of a bronchial atypical carcinoid, the characteristics that led to this phenomenon stay unclear, more studies are needed.

Carcinoid Syndrome Induced B12 Deficiency Resulting in Subacute Combined Degeneration (P9-4.007)

<h3>Objective:</h3> To describe a case of B12 deficiency with an unclear initial workup. <h3>Background:</h3> B12 deficiency is a commonly seen disorder which may present with a myriad of symptoms and neuro-imaging findings. These findings overlap with several other demyelinating and vitamin deficiency disorders making a thorough workup essential. This workup requires testing of several serum markers as well as neuro-imaging to rule out other etiologies of a patient’s symptoms. One such etiology of B12 deficiency is carcinoid syndrome related malabsorption of B12. Adding to the complexity this diagnosis can be a normal/elevated B12 level with an absence of any other clear diagnosis. <h3>Design/Methods:</h3> Case Report <h3>Results:</h3> A fourty-two-year-old patient with carcinoid tumor presented to the hospital with progressive numbness over the previous two years. Workup demonstrated unimpressive CSF studies and serum workup, including an elevated B12 level. Neuro-imaging demonstrated no significant demyelinating findings but with abnormal edema signal with patchy enhancement predominantly in the dorsal columns of the ventral cervical spinal cord. Due to the lack of evidence supporting an alternative diagnosis along with classic MRI findings and a history of recent B12 supplemental injection, the patient was diagnosed with B12 deficiency and discharged home on B12 supplementation with close follow up. After follow up, the patient reported improvement of her symptoms with appropriate B12 supplementation. <h3>Conclusions:</h3> This case highlights the challenge that diagnosing progressive numbness attributable to B12 deficiency can present, along with the myriad of etiologies which may contribute to the diagnosis. It reinforces the importance of detailed history taking with regards to a patient’s medical history, such as carcinoid syndrome, and recent medications taken at home, like B12 injections, which may help delineate a diagnosis or have acutely normalized and hidden a chronic B12 deficiency. <b>Disclosure:</b> Dr. Chilukuri has nothing to disclose. Dr. Houghton has nothing to disclose. Miss Binkley has nothing to disclose.

Typical Pulmonary Carcinoid Tumours and the Relevance of Ki-67 Index: A Tertiary Centre Experience in South Australia

Pulmonary carcinoid tumours are a rare type of neuroendocrine primary lung malignancy. The WHO classifies carcinoids as typical (TC) and Atypical Carcinoid (AC) based on mitotic rate and necrosis on histology [1,2]. It is widely accepted that TC has a better overall prognosis than AC. A higher stage (the presence of nodal or metastatic disease) at presentation is correlated with poorer outcomes [3].

Bronchial Typical Carcinoid with Carcinoid Syndrome Successfully Treated with Everolimus and Octreotide: a Case Report

Background. Bronchopulmonary typical carcinoid tumors with distant metastasis and carcinoid syndrome are rare. Case. We report the case of a 77-year-old woman diagnosed with a bronchial typical carcinoid in the right middle lobe bronchus and multiple liver metastases. The patient presented with facial flushing and diarrhea, and the serotonin blood levels were elevated, indicative of carcinoid syndrome. Combination therapy with everolimus and octreotide maintained the patient in a healthy condition for approximately two years until she died in 2019. Conclusion. Bronchial typical carcinoids with multiple liver metastases and carcinoid syndrome in our patient was well-managed by combination therapy with everolimus and long-acting release octreotide.

Immunohistochemical Approach to the Study of Pulmonary Neuroendocrine Tumors

&#x0D; Background: Tumors that arise from neuroendocrine cells can present throughout the body, most commonly in the gastrointestinal tract and pulmonary systems. Neuroendocrine tumors (NETs) of the lungs account for about 25% of primary lung cancers, as well as 20–25% of primary NETs&#x0D; Objective: To analyze the immune-histochemical aspects of Neuro-endocrine Tumors and apprise the reactivity of various immune-histochemical markers.&#x0D; Methodology: This cross-sectional study was conducted in Pathology Department of Gulab Devi Hospital Lahore from January 2021 to December 2021. Total 112 patients with pulmonary NETs cases diagnosed with medical records patients data, clinical features and radiologic images were obtained and both genders with CT scan findings of lung mass were included in the study. Data was entered and analyzed in SPSS. Gender, diagnosis, techniques etc. were presented as frequency and percentage. Age was presented as mean and SD.&#x0D; Results: The mean age was 45.2+12.1 years. The age range between 20 to 60 years. There were 96(86%) male and 16(14%) female. Typical carcinoid was prevailing in young age group while small cell neuro-endocrine tumor was dominant in older patients. Most of the samples were collected using bronchial biopsy 86(77%), 18(16%) of the samples were collected by CT guided biopsy while 7(6%) were collected by ultrasound guided biopsy and 1(1%) by surgical resection. Patients were diagnosed as small cell lung carcinoma 96(86%), typical carcinoid was the second most common diagnosis 10(9%), large cell lung carcinoma was 4(3.0%) and atypical carcinoid tumor was seen in 2(2%) in cases.&#x0D; Conclusion: SCLC was found to be the predominant pulmonary NET. Chromogranin is less sensitive than synaptophysin, raised Ki67 and TTF1 demarcates SCLC from carcinoid particularly in minute biopsy with obscure morphology.&#x0D; Key words Immunohistochemistry, Neuroendocrine carcinoma, Small cell lung carcinoma.

Multiomic sequencing of paired primary and metastatic small bowel carcinoids

Background: Small bowel carcinoids are insidious tumors that are often metastatic when diagnosed. Limited mutation landscape studies of carcinoids indicate that these tumors have a relatively low mutational burden. The development of targeted therapies will depend upon the identification of mutations that drive the pathogenesis and metastasis of carcinoid tumors. Methods: Whole exome and RNA sequencing of 5 matched sets of normal tissue, primary small intestine carcinoid tumors, and liver metastases were investigated. Germline and somatic variants included: single nucleotide variants (SNVs), insertions/deletions (indels), structural variants, and copy number alterations (CNAs). The functional impact of mutations was predicted using Ensembl Variant Effect Predictor. Results: Large-scale CNAs were observed including the loss of chromosome 18 in all 5 metastases and 3/5 primary tumors. Certain somatic SNVs were metastasis-specific; including mutations in ATRX, CDKN1B, MXRA5 (leading to the activation of a cryptic splice site and loss of mRNA), SMARCA2, and the loss of UBE4B. Additional mutations in ATRX, and splice site loss of PYGL, leading to intron retention observed in primary and metastatic tumors. Conclusions: We observed novel mutations in primary/metastatic carcinoid tumor pairs, and some have been observed in other types of neuroendocrine tumors. We confirmed a previously observed loss of chromosome 18 and CDKN1B. Transcriptome sequencing added relevant information that would not have been appreciated with DNA sequencing alone. The detection of several splicing mutations on the DNA level and their consequences at the RNA level suggests that RNA splicing aberrations may be an important mechanism underlying carcinoid tumors.

Periampullary Adenocarcinoma with Incidental Gastric Carcinoid Tumor: Report of an Extremely Rare Case

Periampullary neoplasms are a heterogeneous group of tumors arising within 2 cm of the ampulla of Vater. Neuroendocrine tumors can originate throughout the entire body from neuroendocrine cells. These neoplasms exhibit deep differences, according to their origin and biological behavior. The synchronous presence of a primary tumor in patients affected by a neuroendocrine tumor is reported in the literature; incidence is variable and the most common site is the gastrointestinal tract. Here we report a case of 68 years old female presented with jaundice, anorexia and weight loss. She was mildly anaemic. Gall bladder was palpable. There was no organomegaly. Her CT scan and MRCP revealed a growth in periampullary region. So she underwent Whipple’s procedure. Histopathological report showed synchronous presence of periampullary carcinoma and a carcinoid tumor in stomach. As the carcinoid tumor was nonfunctioning and very small in size, it was not identified in pre-operative work up. J Shaheed Suhrawardy Med Coll 2021; 13(2): 183-186

Prognosis of Unresected vs Resected Small Pulmonary Carcinoid Tumors

BackgroundPrevious studies have shown that overall survival after lung resection for pulmonary carcinoid tumors is favorable. It is unclear what the prognosis is for observation rather than resection for small carcinoid tumors. MethodsWe queried the National Cancer Database to identify patients presenting with primary pulmonary carcinoid tumors between 2004 and 2017. We included patients with small (<3 cm) primary pulmonary carcinoids, who were observed or underwent a lung resection. To minimize confounding by indication, we used propensity score matching, while accounting for age, sex, race, insurance type, Charlson-Deyo comorbidity score, typical and atypical histology, tumor size, and year of diagnosis. We used Kaplan-Meier survival analyses to compare 5-year overall survival in the matched cohorts. ResultsOf 8435 patients with small pulmonary carcinoids, 783 (9.3%) underwent observation and 7652 (91%) underwent surgical resection. After propensity score matching, surgical resection was associated with improved 5-year overall survival (66% vs 81%, P < .001). No significant difference in overall survival was found between wedge and anatomic resection (88% vs 88%, P = .83). In patients undergoing resection, lymph node sampling at the time of wedge and anatomic resection increased 5-year overall survival (90% vs 86%, P = .0042; 88% vs 82%, P = .04, respectively). ConclusionsSurgical resection of small pulmonary carcinoids is associated with improved survival compared with observation. When surgical resection is performed, wedge and anatomic resection result in similar survival, and lymph node sampling improves survival.

Improving Small Lesion Segmentation in CT Scans using Intensity Distribution Supervision: Application to Small Bowel Carcinoid Tumor.

Finding small lesions is very challenging due to lack of noticeable features, severe class imbalance, as well as the size itself. One approach to improve small lesion segmentation is to reduce the region of interest and inspect it at a higher sensitivity rather than performing it for the entire region. It is usually implemented as sequential or joint segmentation of organ and lesion, which requires additional supervision on organ segmentation. Instead, we propose to utilize an intensity distribution of a target lesion at no additional labeling cost to effectively separate regions where the lesions are possibly located from the background. It is incorporated into network training as an auxiliary task. We applied the proposed method to segmentation of small bowel carcinoid tumors in CT scans. We observed improvements for all metrics (33.5% → 38.2%, 41.3% → 47.8%, 30.0% → 35.9% for the global, per case, and per tumor Dice scores, respectively.) compared to the baseline method, which proves the validity of our idea. Our method can be one option for explicitly incorporating intensity distribution information of a target in network training.

Fully-automated detection of small bowel carcinoid tumors in CT scans using deep learning.

Small bowel carcinoid tumor is a rare neoplasm and increasing in incidence. Patients with small bowel carcinoid tumors often experience long delays in diagnosis due to the vague symptoms, slow growth of tumors, and lack of clinician awareness. Computed tomography (CT) is the most common imaging study for diagnosis of small bowel carcinoid tumor. It is often used with positron emission tomography (PET) to capture anatomical and functional aspects of carcinoid tumors and thus to increase thesensitivity. We compared three different kinds of methods for the automatic detection of small bowel carcinoid tumors on CT scans, which is the first to the best of ourknowledge. Thirty-three preoperative CT scans of 33 unique patients with surgically-proven carcinoid tumors within the small bowel were collected. Ground-truth segmentation of tumors was drawn on CT scans by referring to available 18 F-DOPA PET scans and the corresponding radiology report. These scans were split into the trainval set (n = 24) and the test positive set (n= 9). Additionally, 22 CT scans of 22 unique patients who had no evidence of the tumor were collected to comprise the test negative set. We compared three different kinds of detection methods, which are detection network, patch-based classification, and segmentation-based methods. We also investigated the usefulness of small bowel segmentation for reduction of false positives (FPs) for each method. Free-response receiver operating characteristic (FROC) curves and receiver operating characteristic (ROC) curves were used for lesion- and patient-level evaluations, respectively. Statistical analyses comparing the FROC and ROC curves were alsoperformed. The detection network method performed the best among the compared methods. For lesion-level detection, the detection network method, without the small bowel segmentation-based filtering, achieved sensitivity values of (60.8%, 81.1%, 82.4%, 86.5%) at per-scan FP rates of (1, 2, 4 ,8), respectively. The use of the small bowel segmentation did not improve the performance ( ). For patient-level detection, again the detection network method, but with the small bowel segmentation-based filtering, achieved the highest AUC of 0.86 with a sensitivity of 78% and specificity of 82% at the Youdenpoint. The carcinoid tumors in this patient population were very small and potentially difficult to diagnose. The presented method showed reasonable sensitivity at small numbers of FPs for lesion-level detection. It also achieved a promising AUC for patient-level detection. The method may have clinical application in patients with this rare and difficult to detectdisease.

Primary lung cancer in children and adolescents: Analysis of a surveillance, epidemiology, and end results database.

The incidence of primary lung cancer (LC) in children and adolescence was rare. We analyzed data from a SEER database to better define the incidence, clinical characters, pathology, treatment, and outcomes of rare primary malignant pulmonary tumors in childhood and adolescence. Patients were chosen from the SEER database (SEER*Stat 8.4.0 software) from 2000 to 2019 and all patients were pathologically diagnosed with primary malignant tumors of the lung and bronchus. Demographic characteristics of patients (age, gender, race, primary site, laterality, location, differentiation grade, operation methods, histology, and history of radiotherapy and chemotherapy), as well as TNM stage and survival time, were collected. A total of 301 cases of children ≤19 years of age with a primary malignant pulmonary tumor were reported to the SEER database from 2000 to 2019. There were 143 men (47.5%) and 158 women (52.5%). Whites represented majority of patients (79.7%), followed by Black (13.6%) and others (6.7%). As for the primary site, the main site was the lower lobe (33.2%), followed by the upper lobe (26.9%). Most of the patients (80.4%) underwent surgery. Lobectomy (39.9%) is the main operation method. Only 28 (9.3%) patients received radiotherapy and 112 (37.2) patients received chemotherapy. Carcinoid tumor was the most common histology (29.6%), followed by pulmonary blastoma (PB) (22.3%), mucoepidermoid carcinoma (MEC) (12.3%), adenocarcinoma (10.3%), neuroendocrine tumor (NET) (5.7%), squamous cell carcinoma (SCC) (5.3%), atypical carcinoma (2.3%). The mean follow-up time was 100 months. For the entire group of children and adolescents, the 1-year OS was 89.1%, and the 3-year overall survival (OS) was 79.7%. the 5-year OS was 77.9%, the 10-year OS was 75.7%, and the 15-year OS was 73.9%. And 1-year lung cancer specificity survival (LCSS) was 89.8%, and the 3-year LCSS was 80.4%. the 5-year LCSS was 79.4%, the 10-year LCSS was 77.7%, and the 15-year LCSS was 75.9%. The OS of atypical carcinoma, carcinoid tumor, and MEC were in the top three. Primary LC in children and adolescent were rare and histopathological diverse. Fortunately, children and adolescents with LC had an overall favorable outcome after treatment. Histology, differentiation grade, surgery, TNM stage, and therapeutic modalities have important influence on OS. The further treatment experience of each pathological type would make better evidence-based practice possible.

Typical Carcinoid Tumor Cases Causing Ectopic ACTH Syndrome: Dramatic Response to Surgery.

Although Cushing's Syndrome (CS) is usually caused by pituitary/adrenal adenomas, in the remaining few cases, Adrenocorticotrophic hormone (ACTH) is secreted by extrapituitary neuroendocrine tumors (NET). In typical pulmonary / bronchial carcinoid tumors leading to ectopic ACTH syndrome (EAS). The main principle of treatment is the localization of the ACTH-secreting tumor and its surgical removal. In this case report, we aimed to present two typical carcinoid cases, whose ACTH and cortisol levels returned to normal after lung surgery for ectopic ACTH. One of the cases, a 32-year-old female patient with CS symptoms and signs, was referred to our department after detecting a lesion in the left lower lobe in the thorax CT, which did not show an obvious focus on cranial MRI. The other patient, a 36-year-old male, had previously undergone adrenalectomy for Cushing's syndrome and was admitted to the emergency department due to adrenal insufficiency. The lesion seen in the right lower lobe on thorax CT was evaluated as an ectopic ACTH focus. After the tumors of the patients were resected according to surgical principles, CS clinic regressed, and ACTH and cortisol values returned to normal. Pathological examinations of the surgically resected tumors were reported as typical carcinoid. With surgically removed typical carcinoids tumors, excellent longterm survival results can be achieved and hypercortisolism can be controlled.

223P Surgery versus bronchoscopic cryotherapy for the treatment of lung carcinoid tumors: An overview of 5-year experience

223P Surgery versus bronchoscopic cryotherapy for the treatment of lung carcinoid tumors: An overview of 5-year experience

Mediastinal teratoma with double malignant transformation

We report a case of a 65-year-old woman with retrosternal discomfort, dyspnea, and weight loss in whom the computed tomography showed a multicystic mass with fat content and calcified wall in the anterior mediastinum. After surgical resection, pathological examination revealed synchronous primary colorectal adenocarcinoma and primary carcinoid tumor arising in a mediastinal mature cystic teratoma. Treatment with oxaliplatin and capecitabine was instituted, and subsequent checkups showed no evidence of recurrence. Malignant transformation of mature cystic teratoma is a rare complication that occurs in 1–3% of these tumors and consists of a nongerm cell malignant tumor arising from a preexisting mature teratoma. Any of the constituent tissues of a teratoma has the potential to undergo malignant transformation. In case of limited disease, treatment should be surgical. There is no consensus regarding adjuvant treatment, and the existence of a double neoplastic lineage may complicate the choice of chemotherapy treatment.

Clinical profile, surgical management and outcome of bronchial carcinoids - a single centre experience

Background and objectives: Bronchial carcinoid tumors are neuroendocrine neoplasms that range from low-grade typical carcinoids to more aggressive atypical carcinoids and, therefore demonstrate a wide spectrum of clinical behaviors, histologic features and outcome. The aim of the present study was to investigate the clinical profile, surgical management and outcome of bronchial carcinoids at a single centre over two years period. Materials and methods: Patients with a final histologic diagnosis of bronchial carcinoid tumor were included in the study. Evaluation comprised of clinical history and physical examination, postero-anterior and lateral chest radiographs, and computed tomographic (CT) scans of the chest and upper abdomen (including liver and adrenal glands). Performance status was assessed by the Karnofsky scale. Pulmonary function tests were performed routinely. Results: A total of 18 patients were included in the study. Out of 18 cases, 10 (55.6%) were female and 8 (44.4%) were males. Sixteen (88.9%) patients had typical carcinoid tumor and 2 (11.1%) had atypical carcinoid tumor. The tumor was located in the right lung in 11 (61.1%) and in the left lung in 7 patients (38.9%). Surgeries included 15 standard lobectomies and 3 bronchial sleeve resection. At one month post surgery, there was 13-22% increase in post operative FEV1 in patients who underwent bronchial sleeve resection while in patients who underwent lobectomy, the post operative FEV1 was 84% of pre-operative FEV1. Post surgery, all patients were in group A as per Karnofsky performance status. Conclusion: Standard care of bronchial carcinoid tumors is surgical resection, and the surgical approach should depend on tumor’s size, location and histology. IMC J Med Sci. 2023; 17(2):003. DOI: https://doi.org/10.55010/imcjms.17.013 *Correspondence: Farooq Ahmad Ganie, Department of Cardiovascular and Thoracic Surgery, SKIMS, Soura, Srinagar, Kashmir, India. Email: farooq.ganie@ymail.com

Clinical characteristics and endoscopic findings in autoimmune gastritis – A retrospective study

Abstract Objectives: Autoimmune gastritis (AG) is a rare condition that increases the risk of developing stomach adenocarcinomas or carcinoid tumours. The objectives of the present research were to summarise the clinical traits of AG patients, together with gastroscopic and histopatho-logic findings, demographic data, and hematologic characteristics. Patients and methods: A medical centre assessed 58 AG patients from January 2019 to December 2022. Results: The majority of the patients were female (73.7%), and the mean age of the participants at the time of the diagnosis was 57.7 ± 12.1 years. We identified pernicious anaemia (54.4%), iron deficiency anaemia (21.1%), as well as autoimmune disorders (96.5%). Though 78.9% of patients reported having gastrointestinal symptoms, 69% presented exclusively upper gastrointestinal symptoms, 17% only had lower, and 14% had concurrent upper and lower gastrointestinal symptoms. All 58 AG patients were examined for associated gastric lesions, although abnormal injuries were detected in only 22 of them. One patient (1.8%) had adenocarcinoma, while five patients (8.8%) had type 1 neuroendocrine tumours (NET). In addition, hyperplastic polyps were found in 16 (28.1%) individuals. Conclusions: Other autoimmune diseases were present with AG, which showed a female predominance. Clinicians should give AG more significant thought by allowing access to interdisciplinary teams.

Incidental diagnosis of appendiceal neuroendocrine (carcinoid) tumors during benign gynecologic surgery: a case series

Incidental diagnosis of appendiceal neuroendocrine (carcinoid) tumors during benign gynecologic surgery: a case series

Synthesis and Pharmacological Evaluation of the derivatives of 1,4-dihydropyridine: A Pleiotropic Molecule with Antiulcer activity

As previously researches indicate that 1,4-Dihydropyridine is a versatile molecule and it is clearly shown that it possesses different therapeutic activity in versatile disease. It shows different activity such as anticancer, anticonvulsant, anticoagulant, anti-alzheimer, antitubercular and antiulcer. Various adverse effects of proton pump inhibitors and H2 blockers were reported by many Investigators. These are Gastric cancer, Colon cancer, Gastric carcinoid tumor, gastrointestinal infection and many others. A good antiulcer potential of 1,4 Dihydropyridine with aromatic primary amine substitution seen here, with that reason our research work to conduct synthesis of 1,4 dihydropyridine derivative by replacement with some other aromatic primary amine scaffolds, and to evaluate the antiulcer potency of 1,4 Dihydropyridine. All chemicals were purchased from verified companies. Characterization of these synthesized molecules were performed by various spectroscopic methods and evaluated for in-vivo antiulcerogenic potential by using different animal models. A series of approximately in 25 numbers 1, 4 Dihydropyridine derivatives were synthesized and characterized on their spectroscopic studies. Antiulcer activity was performed in ethanol induced gastric lesions followed with five different models. In series of approximately 25 derivatives synthesized compound A5, A6, B5 and B6 shows significant activity in comparison to standard drug i.e.Omeprazole and among all compound, A5 and B6 (30mg/kg) shown potent antiulcer activity. Our final remark clearly stated that 1,4 Dihydropyridine previously established as calcium channel blocker, must shown antiulcer potential and all synthesized compound can serve as leads for new antiulcer agents after further investigation.

Emerging Immunotherapeutic and Diagnostic Modalities in Carcinoid Tumors.

Evasion of innate immunity represents a frequently employed method by which tumor cells survive and thrive. Previously, the development of immunotherapeutic agents capable of overcoming this evasion has realized pronounced clinical utility across a variety of cancer types. More recently, immunological strategies have been investigated as potentially viable therapeutic and diagnostic modalities in the management of carcinoid tumors. Classic treatment options for carcinoid tumors rely upon surgical resection or non-immune pharmacology. Though surgical intervention can be curative, tumor characteristics, such as size, location, and spread, heavily limit success. Non-immune pharmacologic treatments can be similarly limited, and many demonstrate problematic side effects. Immunotherapy may be able to overcome these limitations and further improve clinical outcomes. Similarly, emerging immunologic carcinoid biomarkers may improve diagnostic capabilities. Recent developments in immunotherapeutic and diagnostic modalities of carcinoid management are summarized here.