A proposed staging system for rectal carcinoid tumors based on an analysis of 4701 patients

Landry, Christine S.; Brock, Guy; Scoggins, Charles R.; McMasters, Kelly M.; Martin, Robert C.G.

doi:10.1016/j.surg.2008.05.005

Cited by 73 publications

(56 citation statements)

References 10 publications

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“…1,2 Similar to the epithelial neoplasms of the gastrointestinal tract, there is significant morphological and immunohistochemical diversity across neuroendocrine tumors of the tubular gut. However, unlike epithelial neoplasms of the gastrointestinal tract little is known about the molecular heterogeneity or genetic underpinnings of neuroendocrine tumors of the tubular gut.…”

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confidence: 99%

Heterogeneity in signaling pathways of gastroenteropancreatic neuroendocrine tumors: a critical look at notch signaling pathway

et al. 2013

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The molecular pathogenesis of gastroenteropancreatic neuroendocrine tumors is largely unknown. We hypothesize that gastroenteropancreatic neuroendocrine tumors are heterogeneous with regard to these signaling pathways and these differences could have a significant impact on the outcome of clinical trials. We selected 120 well-differentiated neuroendocrine tumors including tumors originating in pancreas (n ¼ 74), ileum (n ¼ 31), and rectum (n ¼ 15). Immunohistochemistry was performed on tissue microarrays using the following antibodies: NOTCH1, HES1, HEY1, pIGF1R, and FGF2. Gene profiling study was performed by using human genome U133A 2.0 array and data were analyzed. The gene profiling results were selectively confirmed by using quantitative reverse-transcription PCR. Initial immunohistochemical analysis showed NOTCH1 was uniformly expressed in rectal neuroendocrine tumors (100%), a subset of pancreatic neuroendocrine tumors (34%), and negative in ileal neuroendocrine tumors. Similarly, a downstream target of NOTCH1, HES1 was preferentially expressed in rectal neuroendocrine tumors (64%), a subset of pancreatic neuroendocrine tumors (10%), and uniformly negative in ileal neuroendocrine tumors. Messenger RNAs for NOTCH1, HES1, and HEY1 were 2.32-, 2.44-, and 2.39-folds, respectively, higher in rectal neuroendocrine tumors as compared with ileal neuroendocrine tumors. Global gene expression profiling showed 95 genes were differentially expressed in small intestinal vs rectal neuroendocrine tumors, with changes as high as 50-fold. These genes were concentrated in several signal transduction pathways including cancer endocrine pathway and cell growth/proliferation pathway. The differential expression of selected genes including ISL LIM homeobox 1, cathepsin B, glucagon, and tryptophan hydroxylase 1 were confirmed by qPCR and immunohistochemistry. Our results confirm the heterogeneity in signaling pathways of gastroenteropancreatic neuroendocrine tumors. NOTCH1 inhibitors are unlikely to provide benefit in ileal neuroendocrine tumors; conversely, their efficacy in rectal neuroendocrine tumors needs further study. Further analysis of signaling pathways is critical for designing clinical trials in gastroenteropancreatic neuroendocrine tumors.

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confidence: 99%

Heterogeneity in signaling pathways of gastroenteropancreatic neuroendocrine tumors: a critical look at notch signaling pathway

et al. 2013

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“…Endoscopic treatment was performed prior to surgery in 7 patients (cases 2, 3, 5, 7, 11, 17 and 19). Trans-anal local resection was performed in 4 patients (cases [17][18][19][20] and each of those cases was followed for >70 months (mean, 116), with no recurrence identified at the time of writing. Radical surgery consisting of rectal resection with a lymphadenectomy was performed in 16 (cases 1-16) of the 20 patients (Table II).…”

Section: Resultsmentioning

confidence: 99%

“…Several factors, including tumor size, depth of invasion, presence of lymphovascular invasion, presence of central depression and Ki-67 ratio, have been reported to be associated with metastasis (2)(3)(4)(5)(6)16,17). Tumors smaller than 10 mm in size without infiltration to the proper muscle layer can usually be removed in an endoscopic procedure.…”

Section: Introductionmentioning

confidence: 99%

Clinicopathological characteristics of rectal carcinoid patients undergoing surgical resection

et al. 2012

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Abstract. The aim of this study was to clarify the clinical aspects, histopathological features and prognosis of patients with rectal carcinoids, focusing on properties associated with metastasis, in order to gain insights into appropriate management. A total of 20 patients (15 males, 5 females; mean age, 54.9 years; range, 23-71) who underwent surgery for rectal carcinoid tumors at the Department of Colorectal Surgery, Hyogo College of Medicine, between May 2000 and January 2011 were analyzed. Ki-67 immunostaining was performed in 13 cases with available tumor tissue specimens. Of the 20 patients, a radical operation including rectal resection with a lymphadenectomy was performed in 16. The mean tumor size was 11.9 mm (3-25 mm) and lymph node metastasis was confirmed in 9 cases, including 3 with lesions no greater than 7 mm in diameter. Overall, 16 (80%) of the tumors were localized in the submucosal layer and 4 (20%) involved the proper muscle layer. Ki-67 labeling index and lymphovascular invasion were shown to be associated with lymph node and/or distant metastasis by multiple logistic regression analysis, but were not statistically significant in ANOVA findings. Lymph node metastasis from rectal carcinoids, even those smaller than 10 mm in diameter, was not a rare event. More attention should be given to decision-making, including the possibility of endoscopic resection for the treatment of rectal carcinoid tumors regardless of size.

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“…Tumors between 1 and 2 cms have been traditionally treated by local excision, however recent evidence suggest that tumor size greater than 1 cm along with lympho-vascular invasion and involvement of the muscularis propria is associated with tumor metastases and recurrence. [13,14] Consideration for rectal resection with TME should therefore be given for tumors between 1-2 cms, particularly if other adverse features [15] For left colon WDNET, as these tumors are rare, there is little evidence to identify patients that are LN negative and therefore could be excised endoscopically. Again if the tumor can be removed by polypectomy or EMR with negative margins and is less than 1 cm this would seem a reasonable treatment option.…”

Section: Managementmentioning

confidence: 99%

“…The reported 5 year survival rates for metastatic disease range from 17 to 20 %. [13,24] High Grade Neuroendocrine Carcinomas Compared to WDNET, HGNEC is essentially an entirely different disease. It is occurs much less frequently however behaves much more aggressively much more like the pulmonary equivalent, small cell carcinoma.…”

Section: Managementmentioning

confidence: 99%

Hindgut Neuroendocrine Neoplasia

Smith

Nandakumar

2015

Indian J Surg Oncol

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A proposed staging system for rectal carcinoid tumors based on an analysis of 4701 patients

Cited by 73 publications

References 10 publications

Heterogeneity in signaling pathways of gastroenteropancreatic neuroendocrine tumors: a critical look at notch signaling pathway

Heterogeneity in signaling pathways of gastroenteropancreatic neuroendocrine tumors: a critical look at notch signaling pathway

Clinicopathological characteristics of rectal carcinoid patients undergoing surgical resection

Hindgut Neuroendocrine Neoplasia

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