Ileal Carcinoid Research Articles

Multimodality assessment of cardiac metastasis in a patient with ileal carcinoid.

Multimodality assessment of cardiac metastasis in a patient with ileal carcinoid.

Primary ileal carcinoid presenting with metastatic ovarian tumours and florid carcinoid syndrome: a multidisciplinary care challenge

Primary ileal carcinoid presenting with metastatic ovarian tumours and florid carcinoid syndrome: a multidisciplinary care challenge

S4114 Ileal Carcinoid With Carcinoid Syndrome

S4114 Ileal Carcinoid With Carcinoid Syndrome

Cutaneous metastases of non-cutaneous neuroendocrine neoplasms: A histopathologic review of 15 cases.

Cutaneous metastases from non-cutaneous neuroendocrine neoplasms are rare; however, distinction from primary neuroendocrine carcinomas of the skin (Merkel cell carcinoma) guides clinical management. We performed a retrospective review from September 1, 2010 to September 30, 2020 of the histopathologic, immunohistochemical, and clinical characteristics of metastatic neuroendocrine neoplasms to the skin from non-cutaneous primaries. Fourteen patients were identified for the study (nine males and five females; mean age of 59.5 years). Fifteen skin specimens from 14 patients were available for review. At the time of skin biopsy, a known non-cutaneous neuroendocrine neoplasm was present in 50% of patients. Primary sites of neuroendocrine carcinoma included lung (n=5), terminal ileum (n=2), and one each from prostate, breast, rectum, uterus, esophagus, and sinus, with one unknown (suspected bladder malignancy). Eleven of fourteen patients are dead of disease; one was lost to follow-up. All 15 specimens showed subcutaneous/deep dermal involvement with six involving the papillary dermis and one involving the epidermis. The tumors ranged from well to poorly differentiated. Two of fifteen specimens showed focal CK20 positivity (one metastatic uterine small cell carcinoma and one metastatic ileal carcinoid). TTF-1 was performed in 13 specimens and was positive in six, of which two were of non-pulmonary origin. While immunohistochemical stains, in particular CK20, CK7, and TTF-1, are integral in the workup of confirming the origin of neuroendocrine tumors found in the skin, results vary and are often non-specific for a single primary site. Therefore, complete radiologic imaging as well as clinical correlation should be recommended to further aid in the identification of a non-cutaneous primary neoplasm.

1175 Ileal Carcinoid Tumors Detected During Screening versus Diagnostic Colonoscopy: Comparison of Tumor Characteristics

INTRODUCTION: Small intestinal carcinoid tumors are the most common type of small bowel malignancy observed. Most are indolent and incidentally found in asymptomatic patients undergoing ileal intubation during routine colonoscopy. Our aim was to survey all patients diagnosed with ileal carcinoid and to compare tumor characteristics for those discovered during screening or diagnostic colonoscopy. METHODS: We reviewed all ileal carcinoid tumor cases from 2005-2018. For each case, we recorded patient age, colonoscopy indication at diagnosis, timing of prior colonoscopy (if ever performed), coexistence of adenomatous polyps in the colon, carcinoid tumor size and stage after resection, and disease-free survival. RESULTS: Twenty-nine (29) cases of ileal carcinoid tumor were identified. Mean patient age at diagnosis was 64. In 5 cases, the tumor was initially identified during urgent surgical evaluation of obstructive symptoms and not during colonoscopy. In the remaining 24 cases, tumors were initially detected during colonoscopy with ileal intubation. Of these, 13 were having initial screening or surveillance. The remaining 11 were having diagnostic evaluation of symptoms, abnormal findings on CT imaging, or both. Table 1 compares carcinoid features for cases detected during screening versus diagnostic colonoscopy. A prior colonoscopy was performed within the preceding 10-year period in 11 cases, and of these, only 3 included terminal ileum intubation. Adenomatous colon polyps were found in 11 of 24 patients, with advanced adenomas identified in 3. Tumor size ranged from 0.5 to 3.7 cm (mean 1.8 cm). Lymph nodes were involved in 21 of 24 patients. In the 3 patients without lymph node involvement, tumors were small (0.5, 0.5, 0.6 cm). At diagnosis, only 1 patient had distant metastases and eventually died from tumor complications 42 months later. Another patient died from an unrelated cause at 99 months after diagnosis. Mean survival-to-date for the remaining 22 patients is 57 months with a range of 2-172 months. CONCLUSION: In our series, most patients with ileal carcinoid tumors were initially diagnosed during colonoscopy rather than during urgent surgery. Nearly all carcinoids discovered during colonoscopy were associated with lymph node involvement at the time of diagnosis. Most, however, did not have or develop distant metastases and have enjoyed prolonged survival. No significant differences in carcinoid tumor size or stage were observed between patients having screening versus diagnostic colonoscopy.

CT detection of primary and metastatic ileal carcinoid tumor: rates of missed findings and associated delay in clinical diagnosis.

To determine the rate of missed CT findings of ileal carcinoid tumor prior to pathologic diagnosis and the resultant diagnostic delay. Initially, 74 patients with abdominal and pelvic CT prior to pathologically-proven diagnosis of ileal carcinoid were identified. Patients were excluded when the original CT study (n = 6) or report (n = 4) was not available, resulting in a final cohort of 64 patients (mean age, 58.3years; 29M/35F); 27 (42%) patients had more than one abdominal CT prior to diagnosis. All available CT studies prior to diagnosis were retrospectively reviewed for the presence of the primary ileal tumor and metastatic disease (mesenteric and hepatic). Primary ileal tumors were prospectively missed on at least one CT scan in 64% (32/50) of patients with retrospectively identifiable disease. CT findings of mesenteric spread were missed at least once in 46% (25/54) of cases where present in retrospect. By the final pre-operative CT, hepatic metastases and bowel wall thickening were present in 55% (35/64) and 52% (33/64) of cases, respectively. In patients with missed ileal and/or mesenteric findings resulting in diagnostic delay, mean delay was 40months (range 4-98months). Initial presentation of ileal carcinoid tumor, even with mesenteric involvement, is often missed prospectively at abdominal CT, leading to delay in diagnosis until bowel or mesenteric findings become more obvious, or hepatic metastatic disease manifests. Radiologists should make a concerted effort to evaluate the bowel and mesentery in patients with long-standing vague abdominal symptoms.

Multimodality Imaging of Ileal Neuroendocrine (Carcinoid) Tumor.

OBJECTIVE. The purpose of this article is to provide a multimodality imaging review of ileal carcinoid tumor. CONCLUSION. Ileal carcinoid tumors display a variety of radiologic findings. Delay in diagnosis is common because of initial nonspecific symptoms and subtle imaging findings. Reviewing the multimodality imaging appearance of the primary tumor, metastatic disease, and associated ancillary findings can help improve patient care.

An unusual cause of hypoxia: getting to the heart of the matter

SummaryA 63-year-old female presented to hospital with progressive exertional dyspnoea over a 6-month period. In the year preceding her admission, she reported an intercurrent history of abdominal pain, diarrhoea and weight loss. She was found to be hypoxic, the cause for which was initially unclear. A ventilation–perfusion scan identified a right-to-left shunt. Transoesophageal echocardiography (TOE) demonstrated a significant right-to-left intracardiac shunt through a patent foramen ovale (PFO); additionally severe tricuspid regurgitation was noted through a highly abnormal tricuspid valve. The findings were consistent with carcinoid heart disease with a haemodynamically significant shunt, resulting in profound systemic hypoxia. 24-h urinary 5-hydroxyindoleacetic acid (5-HIAA) and imaging were consistent with a terminal ileal primary carcinoid cancer with hepatic metastasis. Liver biopsy confirmed a tissue diagnosis. The patient was commenced on medical therapy for carcinoid syndrome. She subsequently passed away while undergoing anaesthetic induction for valvular surgery to treat her carcinoid heart disease and PFO.

Visual Vignette

Case Presentation: A 66-year-old male presented with ileal carcinoid. A month before, he had undergone a screening colonoscopy, which identified a 1-cm nodule in the terminal ileum. Biopsy showed low-grade, well-differentiated neuroendocrine tumor (carcinoid). He felt well without diarrhea, flushing, or abdominal pain. He had no other significant medical history. A smoker aunt had throat cancer. Physical examination findings were unremarkable. Gallium-68 dodecanetetraacetic acid tyrosine-3-octreotate (DOTATATE) positron emission tomography/computed tomography (PET/CT) with intravenous contrast was done to accurately stage the carcinoid. Three sites of intense DOTATATE uptake were found (Fig. 1, arrows): (1) terminal ileum (standard uptake value [SUV], 7.0) without associated soft-tissue abnormality; (2) left glossopharyngeal sulcus and left tongue base (SUV, 6.0) associated with asymmetric fullness at this location, mild left oropharyngeal narrowing, and a 2.1-cm left cervical node; and (3) uncinate process of the pancreas (SUV, 10.0) without an associated mass but with fatty atrophy of the pancreatic body and tail. For reference: the average SUV of liver and aorta were 5.4 and 0.5, respectively. What is the diagnosis?

Abstract 2260: Haplotypes of chromosome 17q21.31 affect liver metastasis by small intestinal neuroendocrine tumors

Abstract Neuroendocrine tumors are the most common tumors of the small intestine. Very little is known about genetic changes that cause SI-NETs, which have a very low frequency of mutations. SI-NETs are highly metastatic to the liver, and patients with liver metastases have a five year survival rate of less than 50%. Caucasian patients are more likely to develop metastasis than patients of other races. We have studied a 900 kB inversion at chromosome 17q21.31, which is common to Caucasians but rare in other races. Within a collection of 117 Caucasian patients with ileal carcinoids, patients with the inversion haplotype were significantly less likely to have liver metastasis. A second Caucasian-specific haplotype in this region, beta2, was also tested for potential association with metastasis of ileal carcinoids. Unlike the inversion haplotype, beta2 associates with increased metastasis of ileal carcinoids. We suspect that the fact that the metastasis-promoting beta2 haplotype is more common among Caucasians than the metastasis-suppressing inversion haplotype (44% incidence vs. 33% incidence) is probably why Caucasians wind up with a higher frequency of metastasis than races that carry neither beta2 nor the inversion. Citation Format: Shinta Kobayashi, Edaise da Silva, Tanupriya Contractor, Laura Tang, Chris R. Harris. Haplotypes of chromosome 17q21.31 affect liver metastasis by small intestinal neuroendocrine tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2260. doi:10.1158/1538-7445.AM2017-2260

Ileal neuroendocrine tumor metastasis to pancreas and liver: A case report

Introduction: Neuroendocrine tumors (NETs) formally known as carcinoids tumors are neoplasms that arise from enterochromaffin cells. The NETs most commonly occur in the gastro-intestinal tract and predominately within the ileum. Symptomatic ileal NETs have most likely metastasized to the liver at the time of diagnosis. Pancreatic metastasis from ileal NETs are exceptionally rare. Case Report: A 76-year-old female with a primary ileal carcinoid underwent right hemi-colectomy secondary to bowel obstruction. One-year post bowel resection, the patient presented with carcinoid syndrome, imaging revealed a singular hepatic metastasis (segment 2) and a pancreatic tail mass. After radiologic workup with an abdominal CT, PET and octreotide scan a presumed diagnosis of recurrent metastatic NET was made. Multi-disciplinary rounds discussed the case. Laparoscopic distal pancreatectomy, splenectomy and radiofrequency ablation of the liver tumor were performed. Surgical pathology of the pancreatic mass was consistent with primary ileal carcinoid tumor. Conclusion: Ileal NET metastasis to the pancreas is a rare phenomenon. Metastatic NET management should be discussed with a multi-disciplinary team. R0 resection of primary and metastatic NETs offers the only chance of cure. Loco-regional, systemic therapies, and surgical debulking can offer a survival benefit in un-resectable disease or in cases where resection incurs a high perioperative risk.

A Case of Carcinoid Syndrome with Carcinoid Valvular Heart Disease Treated Successfully

A 39-year-old lady presented in early 2011 with Carcinoid syndrome due to Ileal Carcinoid with liver metastases and Carcinoid valvular heart disease with Right heart failure. Liver resection combined with ethanol injection of Liver metastases was carried out after reduction of Central Venous Pressure by an initial Tricuspid valve replacement (TVR), in a staged manner, with resolution of symptoms. This case highlights the necessity of TVR prior to major Liver resection for Liver metastases in Carcinoid heart disease with Tricuspid regurgitation as well as the value of treating Carcinoid heart disease aggressively.

回腸カルチノイドの4例

本邦では非常に稀である回腸カルチノイドを，過去10年間で4例経験したため報告する．平均年齢55歳（52-57歳），男:2例・女:2例，主訴は便潜血陽性2例・腹痛2例であった．内視鏡所見として，回腸末端に黄色調の粘膜下腫瘍を認め，全例に生検を施行し，術前にカルチノイドの確定診断に至った．CT検査では，2例に所属リンパ節腫大が指摘されたが，遠隔転移は認めず，根治切除が可能と判断し，全例に腹腔鏡下回盲部切除術（D3郭清）を施行した．病理診断は，平均腫瘍径20mm（12-30mm），深達度は固有筋層，全例に近傍の所属リンパ節転移を認め，pT2N1M0，pStage IIIBであった．補助療法は施行せず，4例とも無再発生存中である．

MicroRNA-133a inhibits cell proliferation, colony formation ability, migration and invasion by targeting matrix metallopeptidase 9 in hepatocellular carcinoma.

MicroRNA‑133a (miR‑133a) is downregulated in various types of human malignancy, including hepatocellular carcinoma (HCC), renal cell carcinoma, esophageal squamous cell carcinoma, bladder cancer, ileal carcinoid and rhabdomyosarcoma. The aim of the present study was to examine the effects of miR‑133a on HCC cell proliferation, colony formation, migration and invasion. miR‑133a was transfected into the HCC HepG2 and SMMC‑7721 cell lines and the expression levels of miR‑133a were determined; in addition, cell viability assays, colony formation assays, cell migration assays, cell invasion assays, western blot analyses and luciferase assays were performed in the HCC cell lines. The results demonstrated that miR‑133a significantly inhibited cell proliferation, colony formation, migration and invasion in HepG2 and SMMC‑7721 cells. To the best of our knowledge, the present study also provided the first evidence that miR‑133a directly downregulated the expression of matrix metallopeptidase 9 (MMP‑9) in the HCC cells. In conclusion, the results of the present study indicated that miR‑133a may have suppressed cell proliferation, colony formation, migration and invasion via the downregulation of MMP‑9 in HCC cell lines. Therefore, MMP‑9 may be used for the development of novel molecular markers and therapeutic approaches to inhibit hepatocellular carcinoma metastasis.

Role of computed tomography angiography in detection and staging of small bowel carcinoid tumors.

Small-bowel carcinoid tumors are the most common form (42%) of gastrointestinal carcinoids, which by themselves comprise 70% of neuroendocrine tumors. Although primary small bowel neoplasms are overall rare (3%-6% of all gastrointestinal neoplasms), carcinoids still represent the second most common (20%-30%) primary small-bowel malignancy after small bowel adenocarcinoma. Their imaging evaluation is often challenging. State-of-the-art high-resolution multiphasic computed tomography together with advanced postprocessing methods provides an excellent tool for their depiction. The manifold interactive parameter choices however require knowledge of when to use which technique. Here, we discuss the imaging appearance and evaluation of duodenal, jejunal and ileal carcinoid tumors, including the imaging features of the primary tumor, locoregional mesenteric nodal metastases, and distant metastatic disease. A protocol for optimal lesion detection is presented, including the use of computed tomography enterography, volume acquisition, computed tomography angiography and three-dimensional mapping. Imaging findings are illustrated with a series of challenging cases which illustrate the spectrum of possible disease in the small bowel and mesentery, the range of possible appearances in the bowel itself on multiphase data and extraluminal findings such as the desmoplastic reaction in mesentery and hypervascular liver metastases. Typical imaging pitfalls and pearls are illustrated.

Small Bowel Carcinoids: A Single Surgeon's Experience in Southern India.

Small bowel carcinoid tumours are indolent neuroendocrine tumours usually seen in the 6(th) and 7(th) decades. Most often, they are silent with non-specific symptoms. They generate serotonin, provoking a desmoplastic reaction in the mesentery leading to bowel ischemia and obstruction. While CECT abdomen can help raise suspicion and show regional spread, elevated 24-hour urinary 5-HIAA levels, histopathology and immunohistochemistry for Chromogranin A are confirmatory. To analyse a single surgeon's experience of clinical features and diagnosis of carcinoid tumours of the small intestine. Retrospective study conducted at MS Ramaiah Medical College and Hospital, Bangalore, India. Fourteen cases of carcinoid of the small bowel presenting to our institution over a 9-year period between December 2005 and November 2014 comprised the study. This included 10 males to 4 females aged 43 to 67 years (Mean: 54.4 years). The patients were investigated using x-ray abdomen, barium study, CECT abdomen, colonoscopy and 24-hour urinary 5- HIAA levels. All patients were surgically treated and histological examination of the resected tumours and immunohistochemistry for Chromogranin A was performed. Twelve patients with ileal carcinoids presented with long standing intestinal colic and sub-acute obstruction. Two patients with jejunal carcinoids had epigastric pain. X-ray abdomen was suggestive of small bowel obstruction in 12 patients. CECT abdomen done in 6 patients, showed ileal narrowing causing proximal dilatation; and cocooining of ileal loops at ileo-caecal junction in 2 cases. Ten patients underwent segmental resection-anastomosis of the tumour-bearing intestine while 4 patients underwent a right hemicolectomy. Lymph node spread was seen in 8 patients of whom 4 had liver metastases. Histopathology and Chromogranin A positivity confirmed the diagnoses. Postoperatively, 24-hour urinary 5-HIAA was mildly elevated in 2 patients. 12 patients were disease free at mean follow up of 4.3 years. 2 patients died due to inanition at 3 and 5 months postoperatively. Carcinoid tumours of small intestine are uncommon in southern India. But they should be considered as differential diagnosis when intestinal tuberculosis is suspected in the elderly presenting with intestinal colic or sub-acute obstruction. They are associated with good prognosis after adequate resection.

Post-surgical surveillance of locally advanced ileal carcinoids found by routine ileal intubation during screening colonoscopy: a case series

IntroductionCarcinoid tumors are the most common type of small bowel tumor, and the incidence is rising. The majority of small bowel carcinoid tumors arise within 60cm of the ileocecal valve. The addition of ileoscopy to screening colonoscopy can detect asymptomatic small bowel carcinoid tumors and improve long-term prognosis through early surgical resection. Ileoscopy is a brief procedure with a high success rate and minimal complications beyond those of colonoscopy. The use of ileoscopy during screening colonoscopy has led to an increase in the early-stage detection of locoregional small bowel carcinoid tumors that can be completely treated with surgery alone, and as such has improved long-term prognosis in these patients.Case presentationsFive asymptomatic Caucasian patients, 3 males and 2 females, from 53 to 70 years old (mean age, 60 years old), were diagnosed with locoregional ileal carcinoids during routine colonoscopy with ileoscopy. Since having an ileocolectomy and without adjuvant treatment, no patient has developed tumor recurrence over a follow-up period of one and half to 12 and a half years.ConclusionThe early detection of carcinoid tumors by ileoscopy during screening colonoscopy can lead to increased long-term survival in patients with locally invasive disease. The high success rate and brief duration of the procedure, in addition to the lack of associated morbidity and mortality suggest that with further studies, routine ileoscopy during colonoscopy may be promising in the diagnosis of small bowel carcinoid tumors.

Looking beyond lymph nodes: Beware of the lurking pseudoaneurysm!

An arteriovenous fistula of the superior mesenteric vessels leading to pseudoaneurysm formation is rare and most commonly occurs after blunt trauma or surgery. We describe a case of a superior mesenteric artery–superior mesenteric vein (SMA/SMV) pseudoaneurysm that was initially misinterpreted as an enlarging hypervascular nodal metastasis on surveillance computed tomography (CT) in a patient who had undergone ileal carcinoid resection. When the case was discussed at the specialist multidisciplinary meeting to consider surgical resection, it was noted that the apparent “hypervascular node” on CT had a signal void character on magnetic resonance imaging, which is atypical for a lymph node. Coronal CT reformat demonstrated a vascular origin from the superior mesenteric trunk. This resulted in the correct diagnosis of a pseudoaneurysm secondary to an SMA/SMV fistula. This avoided an unnecessary repeat surgery, and the patient underwent endovascular repair. In our patient, the distal was closed by 3-mm coils and the proximal was closed by an Amplatzer plug with successful results. Hence, it is crucial for radiologists to have a systematic approach and understanding of vascular-related abnormalities to avoid misdiagnosis that can potentially lead to unwanted morbidity.

Incidentally Detected Ileal Carcinoids During Colonoscopy: A Case Series

Introduction: Incidentally detected small intestinal carcinoids are less frequently associated with distant metastasis when compared to symptomatic tumors. The importance of this cannot be understated because the impact of distant metastases on 5-year survival in these patients is quite dramatic (74% vs 40%). We report a series of 3 cases of small bowel carcinoid tumors incidentally detected at the time of ileal intubation during colonoscopy. Our first patient was a 74-year-old male with a family history of colon cancer in whom screening colonoscopy revealed a 2-cm submucosal lesion in the terminal ileum. Mucosal biopsies were negative for malignancy. Subsequently, an octreotide scan showed significant radiotracer uptake within the terminal ileal mass. He underwent a right hemicolectomy and surgical pathology demonstrated a low-grade pT2N1 malignant carcinoid with local mesenteric spread. He has now been disease-free for 2 years since the surgery. The second patient was a 46-year-old female who underwent a colonoscopy as part of her diagnostic work-up for iron-deficiency anemia. Colonoscopy revealed a 2-cm polyp in the terminal ileum. Mucosal biopsies revealed nests of neuroendocrine cells suspicious for a carcinoid tumor. Her octreotide scan was negative. A right hemicolectomy was successfully performed and surgical pathology revealed a 0.7-cm well-differentiated pT3N0 ileal carcinoid tumor. She is currently disease-free at 6 months of follow-up. Our third patient was a 45-year-old-female with a history of bilateral breast cancer status post bilateral mastectomy, who underwent a screening colonoscopy because of her increased risk of neoplasia secondary to positive BRCA 1 and 2 mutations. The colonoscopy revealed a firm, white, subcentimeter submucosal nodule in the terminal ileum. Mucosal biopsies were consistent with a neuroendocrine tumor and she underwent a successful ileocecectomy with ileocolic anastomosis. Surgical pathology revealed a pT1N0 well-differentiated ileal carcinoid tumor. She is doing well, with no recurrence of disease 18 months after her surgery. The usefulness of routine ileal intubation during colonoscopy is widely debated. Based on our cases, one could argue that it should be attempted in all cases. However, ileal intubation can be technically challenging and may inadvertently prolong colonoscopy procedure time. In view of the relative rarity of significant endoscopic findings in the terminal ileum in patients undergoing screening colonoscopy, the diagnostic yield and efficiency of ileal intubation in these patients should be studied in a large multi-center patient cohort.

HIF signaling pathway in pheochromocytoma and other neuroendocrine tumors.

Hypoxia-inducible factors (HIFs) are transcription factors controlling energy, iron metabolism, erythropoiesis, and development. Dysregulation of these proteins contributes to tumorigenesis and cancer progression. Recent findings revealed the important role of HIFs in the pathogenesis of neuroendocrine tumors, especially pheochromocytoma (PHEO) and paraganglioma (PGL). PHEOs and PGLs are catecholamine-producing tumors arising from sympathetic- or parasympathetic-derived chromaffin tissue. To date, eighteen PHEO/PGL susceptibility genes have been identified. Based on the main signaling pathways, PHEOs/PGLs have been divided into two clusters, pseudohypoxic cluster 1 and cluster 2, rich in kinase receptor signaling and protein translation pathways. Recent data suggest that both clusters are interconnected via the HIF signaling and its role in tumorigenesis is supported by newly described somatic and germline mutations in HIF2A gene in patients with PHEOs/PGLs associated with polycythemia, and in some of them also with somatostatinoma. Moreover, HIFalpha signaling has also been shown to be upregulated in neuroendocrine tumors other than PHEO/PGL. Some of these tumors are components of hereditary tumor syndromes which can be associated with PHEO/PGL, but also in ileal carcinoids or melanoma. HIF signaling appears to be one of the crucial players in tumorigenesis, which could suggest new therapeutic approaches for treatment of neuroendocrine tumors.