Small Bowel Carcinoid Tumors Research Articles

Radiopathological review of small bowel carcinoid tumours

Small bowel carcinoid tumours are endocrine tumours of the gastrointestinal tract. This pictorial essay will review the pathology, clinical features, treatment and prognosis and illustrate the radiographic, computed tomographic, sonographic, magnetic resonance and nuclear medicine appearances of small bowel carcinoid tumours.

A proposed staging system for small bowel carcinoid tumors based on an analysis of 6,380 patients

A proposed staging system for small bowel carcinoid tumors based on an analysis of 6,380 patients

A proposed staging system for small bowel carcinoid tumors based on an analysis of 6,380 patients

Background Little is known about the long-term prognosis of small bowel carcinoids because currently no staging system exists. Methods A search of the Surveillance, Epidemiology and End Results (SEER) database identified 6,380 patients with small bowel carcinoid tumors from 1977 to 2004. Patients were analyzed according to various clinicopathologic factors and a tumor (T1, T2, T3), lymph node (N0, N1), and metastasis (M0, M1) staging system was created according to these parameters. Results Among the 6,380 patients, 2,985 women and 3,395 men, with a median age of 66 years (range 14–98), the median tumor size was 1.9 cm (range .1–30 cm). Multivariate analysis demonstrated that age, size of the primary tumor, and depth of invasion were significant factors. Four stages were created according to statistically significant prognostic factors: 13% of patients were classified into stage I, 31% into stage II, 16% into stage III, and 40% into stage IV. Five-year survival rates were 96%, 87%, 74%, and 43% for stages I through IV, respectively. Conclusions The newly developed TNM staging system accurately discriminates prognosis for small bowel carcinoid tumors.

Le DOTATOC-( 68Ga) pour l’imagerie TEP des tumeurs endocrines digestives : présentation d’un cas et revue de la littérature

68Ga is a positron emitter, obtained from a 68Ge/ 68Ga generator, which can be used to label peptides of clinical interest. DOTATOC is a tracer of high affinity for the type 2 somatostatin receptors and is used for imaging of tumours which are expressing them, including endocrine tumours. We report on the case of a patient with a history of small bowel carcinoid tumour with hepatic metastases, treated by somatostatin analogues, in whom somatostatin receptor scintigraphy showed three liver foci and DOTATOC-( 68Ga) PET/CT highlighted much more liver lesions. Two recent studies emphasised on the superiority of DOTATOC-( 68Ga) PET over somatostatin receptor scintigraphy, and its complementarity with CT, especially for the diagnosis of bone metastases. DOTATOC-( 68Ga) PET/CT, which associates the specificity of somatostatin receptor scintigraphic detection with the spatial resolution of PET and the anatomical precision of CT, seems to be promised to a brilliant future, the more so as it offers many advantages to the patient: a shorter waiting time, one single image acquisition and a satisfying dosimetry.

High‐resolution analysis of genetic alterations in small bowel carcinoid tumors reveals areas of recurrent amplification and loss

Carcinoid tumors of the small intestine are characterized by an indolent clinical course, secretion of neuropeptides, and resistance to standard cytotoxic chemotherapy. To evaluate the molecular events underlying carcinoid tumorigenesis, we used high-resolution arrays of single nucleotide polymorphisms to study chromosomal gains and losses in 24 primary and metastatic small bowel carcinoid tumors derived from 18 patients. Regions of gain or loss comprising whole chromosomes or large chromosomal regions constituted the most common class of anomalies. Loss of all or most of chromosome 18 was the commonest finding, evident in 11 of the 18 cases. Heterozygosity was also lost on chromosome arms 9p and 16q. The amplitude of observed gains was modest in comparison to those reported in some other tumor types. One focal region of recurrent gain on 14q mapped to the locus of the gene encoding the antiapoptotic protein DAD1, and immunohistochemical staining confirmed DAD1 protein expression in tumor samples. This detailed study of an uncommon neoplasm provides a basis to investigate putative oncogenes and tumor suppressor genes in intestinal carcinoid tumors.

Diagnostic and Therapeutic Approach to Small Bowel Carcinoid Tumor. Case Report

Diagnostic and Therapeutic Approach to Small Bowel Carcinoid Tumor. Case Report

Multifocal small-bowel carcinoid tumor causing obscure recurrent gastrointestinal bleeding diagnosed by capsule endoscopy

A 38-year-old woman presented to our hospital with a 2-day history of passing black tarry stools. She had a history of recurrent obscure gastrointestinal bleeding, manifested by hematochezia and iron-deficiency anemia for 2 years, and had had six negative upper endoscopies and six negative colonoscopies prior to this presentation. A small-bowel series and computed tomography of the abdomen were both negative. Because conventional studies failed to find a source of bleeding and because the bleeding persisted, the patient was referred for a small-bowel video capsule endoscopy (Given Imaging Ltd., Yoqneam, Israel). The study was limited due to prolonged retention of the capsule in the stomach but nevertheless it revealed multiple submucosal masses in the distal ileum, some of which were umbilicated and ulcerated, with stigmata of recent bleeding ([Fig. 1], Videos 1, 2).

Carcinoid Tumor of Small Bowel and Colonic Adenocarcinoma, a Concurrent Occurrence in a 77 Year Old Male

Carcinoid Tumor of Small Bowel and Colonic Adenocarcinoma, a Concurrent Occurrence in a 77 Year Old Male

Intermittent Bowel Obstruction Due to a Retained Wireless Capsule Endoscope in a Patient with a Small Bowel Carcinoid Tumour

A 43-year-old man with a history of metastatic carcinoid disease is presented. The patient had symptoms of chronic intermittent abdominal pain two years after undergoing a wireless capsule endoscopy procedure. Radiological examinations revealed a retained capsule endoscope, and the patient underwent exploratory laparotomy with capsule retrieval. To the authors' knowledge, this is the first case presentation of chronic, partial small bowel obstruction caused by unrecognized retention of a capsule endoscope.

Association of DNA methylation and epigenetic inactivation of RASSF1A and beta-catenin with metastasis in small bowel carcinoid tumors

We analyzed promoter methylation of RASSF1A, CTNNB1, CDH1, LAMB3, LAMC2, RUNX3, NORE1A, and CAV1 using methylation-specific PCR in 33 cases of small bowel carcinoid with both matched primary and metastatic tumors. The methylation status of RASSF1A and CTNNB1 were also determined in six primary appendiceal carcinoid tumors. Two neuroendocrine cell lines, NCI-H727 and HTB-119, were analyzed for promoter methylation. Immunohistochemical analyses for RASSF1A and beta-catenin were performed in 28 matched primary and metastatic tumors. Western blot analysis for RASSF1A and beta-catenin was also performed. Normal enterochromaffin cells were unmethylated in all eight genes examined. RASSF1A and CTNNB1 were unmethylated in appendiceal carcinoids. Methylation of RASSF1A and CTNNB1 promoters was more frequent in metastatic compared to primary tumors (p = 0.013 and 0.004, respectively). The NCI-H727 and HTB-119 cells lines were methylated in the RASSF1A promoter region, and after treatment with 5-aza-2'-deoxycytidine (5-AZA), RASSF1A mRNA was expressed in both cell lines. Western blot results for RASSF1A and beta-catenin supported the methylation-specific PCR findings. The other six genes did not show significant differences. These results suggest that increased methylation of RASSF1A and CTNNB1 may play important roles in progression and metastasis of small bowel carcinoid tumors.

Peritoneal carcinomatosis from a small bowel carcinoid tumour

BackgroundPeritoneal carcinomatosis from a gastrointestinal carcinoid tumour is rare and the long-term management and prognosis have not been clearly defined. The natural history is different from gastrointestinal adenocarcinoma, although its capacity to invade regional lymph nodes and generate distal metastasis can make the management more complex. Whilst the development of carcinomatosis is uncommonly reported, it may be higher than expected.Case presentationA 63 years-old woman underwent emergency surgery in 1993 for right iliac fossa pain and a mass that was found to be an ileal carcinoid tumour. Over the next ten years, further surgery was required for disseminated disease with peritoneal carcinomatosis and liver metastasis. Systemic chemotherapy had little effect, although Somatostatin was used effectively to relieve symptoms caused by the disseminated disease (flushing and diarrhoea).ConclusionPeritoneal carcinomatosis from carcinoid tumours is not well documented in the literature. Aggressive surgery must be performed in order to control the disease since chemotherapy has not been reported to be effective. With repeated surgery long-term survival can be achieved in these patients.

Carcinoide intestinal múltiple: Análisis de un caso y revisión de la literatura

Small bowel carcinoid tumors are more common in the distal ileum and they are multiple in 30% of cases. The most common clinical manifestation is abdominal pain and the treatment of choice is surgical excision. We report a 63 years old female consulting for abdominal pain. An intestinal transit by computed axial tomography revealed multiple images compatible with small bowel carcinoid tumors. She had a surgical excision of the involved intestinal segment and the pathological study confirmed the imaging diagnosis. In the follow up, this patients has been asymptomatic.

Retention of the Capsule Endoscope

Purpose: Capsule endoscopy (CE) permits direct and painless visualization of small bowel mucosa. It has become a powerful imaging modality in evaluating diseases of the small bowel. Retention of the capsule is one of the most significant potential complications. We aimed to determine the incidence and causes of capsule retention and to investigate the clinical outcomes after capsule retention. Methods: A retrospective review of all patients undergoing CE from June 2002- March 2006 was carried out. Demographics, indication for the CE study, causes of retention found on surgery, and post-operative clinical outcomes were extracted. Results: One thousand patients underwent CE for suspected small bowel disease. Eleven patients (1.1%; 1 male, 10 female; average age 60) were found to have radiologically confirmed capsule retentions. The indication for CE was obscure gastrointestinal bleeding in 8 patients and suspected Crohn's disease in 2 patients. One patient underwent CE for evaluation of possible radiation enteritis associated abdominal pain. Eight patients failed to pass the capsule because of small bowel strictures due to NSAID enteropathy (diaphragm disease). Two patients had capsule retention due to obstructing small bowel carcinoid tumors. Metastatic ovarian cancer with invasion of the ileum was the cause of retention in another patient. All patients remained “asymptomatic,” despite retention of the capsules. Ten patients underwent elective partial small bowel resection and capsule removal. No mortality was associated with these surgeries. Two patients developed mild post-op ileus. Conclusions: Capsule retention in clinical practice appears to be low. In most cases, capsule retention is asymptomatic and is unlikely to cause acute obstruction. Capsule retention always occurs at the site of pathology, therefore surgical removal usually leads to identification and treatment of the underlying small bowel disease. Most common cause of retention in our center appears to be diaphragm disease due to NSAIDs followed by small bowel tumors.

A Novel External Lead Sensor Array Placement Approach for Capsule Endoscopy

A Novel External Lead Sensor Array Placement Approach for Capsule Endoscopy Gary Chen, Oren Goltzer, Jason Shen, Christopher Chang, Shahab Mehdizadeh, James Sul, Rome Jutabha Background: Capsule endoscopy (CE) of the small bowel (SB) & esophagus (ESO) requires placement of 8 lead sensor array over the abdomen that receives image and localization data transmitted from the capsule. This current process of applying lead sensor array to the skin has disadvantages: 1) it is time consuming, and 2) it can be uncomfortable to the patient. We hypothesized that a new external sensor array system could adequately receive transmitted images during CE without significant data loss and have equivalent diagnostic yield with standard skin leads. Methods: We tested this new device on 13 patients from 8/2005-11/2005. 8 patients underwent esophageal CE for GERD and 5 had small bowel CE for OGIB. All 13 patients had 2 sets of sensor arrays, batteries, and data recorders placed concurrently. The standard array was placed on the skin surface of the chest or abdomen in the usual manner (control) while the external array was pre-positioned on a gown that was worn over the skin leads. The total number of captured versus dropped images recorded by the skin and external lead systems were compared visually and then analyzed statistically. Results: 8/8 GERD patients had grade 1-2 reflux esophagitis on CE ESO. 4/5 OGIB patients had small bowel AVM’s while 1 patient had a small bowel carcinoid tumor on CE SB. The same final diagnoses were made on all 13 patients by both standard and novel external lead methods. For the 13 patients, a total of 313793 images were detected on CE procedures with the standard method while 311169 images were detected with the novel external method (99.2% of the control). All of the non-captured images missed by the external array leads occurred in short segments (4-5 frame segments); no prolonged stretches of missing data occurred with either method. The quality of captured CE images was identical between the 2 methods, but CE localization tracings were different, presumably related to movement of the leads during the recording period. Most of the patients preferred the novel external method because of less skin irritation and discomfort during the lead removal process, as well as shorter setup time without the need of removing clothing. Conclusion: 1) A pre-positioned external lead sensor array can achieve CE data without clinically significant loss of image quality and diagnostic yield, 2) localization tracings for CE SB are different due to movement of the external array, 3) more patients preferred the novel external method than the standard method. These preliminary results must be confirmed with larger sample size.

Incidence of Small Bowel Cancer in the United States and Worldwide: Geographic, Temporal, and Racial Differences

To examine the demographic and geographic patterns of small bowel cancer incidence in the United States and worldwide. Incidence data from the Surveillance, Epidemiology, and End Results (SEER) program between 1973 to 2000 were used to analyze the four histologic types of small bowel cancer, adenocarcinomas, carcinoid tumors, lymphomas, and sarcomas. International comparisons were made using data from Cancer Incidence in Five Continents (CIVIII). Geographic correlations between small bowel and both large bowel and stomach cancer incidence, were performed. Men had higher rates than women for all types of small bowel cancer. Blacks had almost double the incidence of carcinomas and carcinoid tumors compared to whites (10.6 vs. 5.6 per million people; 9.2 vs. 5.4 per million people, respectively). Small bowel cancer incidence has risen, with the greatest increase for carcinoid tumors (21%) and black men (120%). A geographic correlation between small and large bowel cancer incidence, but not small bowel and stomach cancer, were observed. Small bowel cancer incidence in the U.S. is higher in blacks compared to whites, particularly for carcinomas and carcinoid tumors. Small bowel cancer incidence is rising, particularly in black men. The geographic correlation between large and small bowel cancer suggests shared etiologies.

The Capsule Identifies Obscure Primary Carcinoids in the Small Intestine

Purpose: Carcinoid tumors are a heterogeneous group. Midgut carcinoid accounts for approximately 50% of all carcinoid tumors in adults, the majority of which arise in the ileum. Since the clinical symptoms are often vague and unrecognized until disease becomes advanced, a majority of patients have metastatic disease at time of diagnosis. It is important to determine the location of the primary since, to a considerable degree, it directs management and predicts outcome. The aim of this study was to assess the utility of wireless video capsule endoscopy in identifying a suspected intestinal primary in patients with demonstrated metastatic carcinoid and no detectable primary on standard investigation. Methods: A retrospective chart review was performed and 24 patients with metastatic carcinoid of unknown primary origin were encountered. Patients' baseline characteristics, clinical presentations, radiological evaluations, chemistries, and therapies were all recorded. All patients underwent wireless video capsule endoscopy in search of a primary lesion after having negative localizing or nonspecific findings on EGD/Colonoscopy, Small Bowel Series, CT scan and OctreoScan®. Results: Of the 24 patients, 8 (33.3%) had positive findings on capsule examination, suggesting a primary carcinoid tumor. All had previously diagnosed metastatic carcinoid on needle biopsy. 5 of these (62.5%) had an ileal primary, 1 (12.5%) had a jejeunal primary, and 2 (25%) were simply classified as a mid small bowel primary. In all cases this positive finding changed management. 7 of the 8 patients (87.5%) underwent surgery and had confirmed small bowel carcinoid tumors. 1 patient who had very advanced disease and was not operated upon had a change in his chemotherapy regimen after the positive capsule finding. Of the 16 patients who had negative capsule studies, 6 had metastatic carcinoid diagnosed by liver biopsy, 1 had an orbit biopsy, 1 had a mesenteric mass biopsy, 1 had a lymph node biopsy, and 3 had significantly abnormal chemical markers (urine 5-HIAA, chromogranin A, and serotonin) strongly indicating carcinoid. No primary was found in 12 of the 16 patients, whereas in 4 patients the primary was proven by biopsy to be in the pancreas. Conclusions: We conclude that wireless video capsule endoscopy is useful in detecting carcinoid tumors originating in the small bowel and not detected by any other conventional method. This localization is significantly important in directing treatment and management of these patients.

Microsatellite instability and gene mutations in transforming growth factor‐beta type II receptor are absent in small bowel carcinoid tumors

Microsatellite instability (MSI) with concomitant mutations in the coding region of transforming growth factor-beta type II receptor (TGFbetaRII) results in an aberrant growth-regulatory phenotype in colorectal carcinomas. The authors postulated that a similar mechanism occurred during the malignant evolution of small bowel carcinoid tumors. Mutational analysis of two coding regions in the TGFbetaRII gene associated with MSI and BAT-26 within intron 5 of the mismatch repair gene, hMSH2, was undertaken in small bowel carcinoids (n = 14), lymph node metasasis (n = 1) and liver metastases (n = 5). Quantitative PCR analysis [TAQMAN, Applied Biosystems, Foster City, CA] was then undertaken to examine gene alterations in mismatch repair genes (hMLH1 and hMSH2) in small bowel carcinoids (n = 7) and matched normal mucosa (n = 5). Staining was then analyzed using quantitative tissue array profiling (AQUA analysis) in a small bowel EC carcinoid tissue microarray (n = 55 tumors) with immunostaining against TGFbetaRII and MSH2. Mutational examination of the TFGbetaRII gene and BAT-26 demonstrated that MSI was not present in any carcinoid material. Q RT-PCR analysis demonstrated statistically significant increased message levels of hMSH2 but not hMLH1 in carcinoid tumors. Quantitative analysis of membrane TGFbetaRII immunostaining using AQUA demonstrated that TGFbetaRII expression was down-regulated (P < 0.0002) in thirty-three primary small bowel carcinoids that exhibited lymph node and liver metastases compared to normal mucosa. AQUA analysis of nuclear MSH2 immunostaining demonstrated no differences for MSH2 between normal tissue and carcinoid tumor metastasis. Small bowel carcinoids characterized by variable expression of TGFbetaRII, did not exhibit MSI and had no differences in MSH2 expression. The molecular events leading to the formation of carcinoid tumors in the small bowel were different from those resulting in epithelial carcinomas. The usually slow-growing and relatively nonaggressive carcinoid tumors had variable expression of TGFbetaRII but were associated with the retention of mismatch repair protein function and a microsatellite-stable phenotype.

Carcinoid Tumors and Fibrosis: An Association with No Explanation

Carcinoid tumors are slow-growing neuroendocrine neoplasms most commonly associated with the gut and broncho-pulmonary system. In many instances, they are identified at surgery for unexplained bowel obstruction or during exploration of the small bowel in search of a primary tumor once distant metastases have been detected. Carcinoid tumors of the small bowel often present with pronounced fibrosis in the peri-tumoral tissues, distant in the heart or lungs, and locally in the peritoneal cavity. Despite medical and therapeutic advances that have alleviated symptoms and prolonged life, a substantial subset of patients develops mesenteric and small bowel carcinoid fibrosis and/or carcinoid heart disease. Fibrosis, and increasingly cardiac heart disease, are important components of intestinal carcinoid disease and are of considerable clinical concern, as both of these conditions reflect a connective tissue disorder whose etiology, biology, and therapy are unknown. In the past, individuals with carcinoid disease died of metastasis and uncontrollable symptomatology. Currently, there exists no clinical method to determine the development of fibrosis and little is understood about the biological basis of fibrosis. The elucidation of the biology and management of fibrosis is thus an issue of paramount clinical and scientific importance in determining appropriate diagnostic and therapeutic strategy. Therefore, the unraveling of the molecular events indicative of fibrosis in these cells and the identification of appropriate therapeutic targets is of considerable patient-care relevance. We have surveyed the world literature over the past 40 yr to evaluate both the incidence of carcinoid processes and track the evolving understanding of this process. In addition, we have provided more current mechanistic information in regard to the biological basis of fibrosis associated with small bowel carcinoid tumors.

Carcinoid Tumor of the Jejunum with Perforation

Perforation is a rare complication of intestinal carcinoid tumor. Only 11 cases have been reported in the literature and most of them were located at the ileum, appendix, and Meckel's diverticulum. A 71-year-old woman presented with postprandial abdominal fullness and complained of significant body weight loss within the previous two months. During admission, she was suffering from acute abdomen. Computed tomography showed free air in the abdomen. Urgent exploratory laparotomy disclosed a predominantly submucosal tumor extending through the thickness of the muscle layer and mucosa with transmural perforation at the jejunum. Histopathological and immunohistochemical studies were typical of carcinoid tumor. We herein report perforation of a small bowel carcinoid tumor at an unusual site.

The importance of smoking and medical history for development of small bowel carcinoid tumor: a European population-based case-control study.

Little is known about the etiology of small bowel carcinoid tumor (SBC), but a few studies have pointed to certain medical and lifestyle factors as potential risk factors. This study aims to evaluate these findings and to identify new associations. A population-based European multicenter case-control study was conducted from 1995 through 1997. Incident histologically verified 35-69 year-old SBC cases (n = 99) and 3335 controls were recruited; 84 cases and 2070 controls were interviewed. Ever being a smoker was associated with SBC (odds ratio = 1.9; 95% confidence interval 1.1-3.2) and increased risk estimates were seen for all smoking categories. SBC was associated with previous gallstone disease and ovariectomy, but only when these conditions occurred within two years prior to the SBC diagnosis. No association was seen for a history of cholecystitis, liver cirrhosis, ulcerative disease, or Crohn's disease. Intake of alcoholic beverages--as well as medical treatments with radioactive substances, hormones, or corticosteroid tablets--were not associated with SBC. This study indicates that tobacco smoking is a risk factor for SBC. The associations with gallstone and ovarian diseases may be due to enhanced medical surveillance during the early phase of the cancer disease.