Ileal neuroendocrine tumors detected during screening or diagnostic colonoscopy – case series and comparison of tumor characteristics.

doi:10.21203/rs.3.rs-2086473/v1

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Ileal neuroendocrine tumors detected during screening or diagnostic colonoscopy – case series and comparison of tumor characteristics.

https://doi.org/10.21203/rs.3.rs-2086473/v1

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Journal Publication

published 26 Dec, 2022

Read the published version in Journal of Gastrointestinal Cancer →

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Purpose: Small intestinal neuroendocrine tumors are the most common type of small bowel malignancy observed. Ileal tumors are often found in patients undergoing ileal intubation during colonoscopy. Our aim was to compare ileal neuroendocrine tumor characteristics when discovered during screening versus diagnostic colonoscopy.

Methods: We reviewed all ileal neuroendocrine tumor cases from 2005-2021. We recorded patient age, gender, colonoscopy indication at diagnosis, timing of prior colonoscopy (if ever performed) and whether ileal intubation was performed, tumor size and stage after resection, and disease-free survival.

Results: Twenty-eight ileal neuroendocrine tumor cases were diagnosed at colonoscopy. Fifteen patients were having initial screening or surveillance. The remaining 13 were having diagnostic evaluation of symptoms, abnormal CT imaging, or abnormal stool test results. A prior colonoscopy was performed within the preceding 10-year period in 14 cases, and of these, 8 did not include terminal ileum intubation. Tumor size ranged from 0.5 to 3.7 cm and mean size was nearly identical in screening and diagnostic groups (1.7 vs 1.9 cm). Lymph nodes were involved in 25 of 28 patients. At diagnosis, 2 patients had distant metastases. Mean survival-to-date was similar for both groups as well (85 vs 88 months).

Conclusion: Nearly all ileal neuroendocrine tumors discovered during colonoscopy were associated with nodal metastasis at the time of diagnosis. Most, however, have enjoyed prolonged survival. No significant difference in tumor size, stage, or survival was observed between patients having screening versus diagnostic colonoscopy. Our findings support performing routine ileal intubation during colonoscopy for all indications.

neuroendocrine tumor

small intestine

ileum

colonoscopy

Neuroendocrine tumors (NETs) are the most common type of small bowel malignancy. [1] Most occur within 60 cm of the terminal ileum and have a greater propensity for nodal or distant metastasis at time of diagnosis relative to NETs originating from other sites. Ileal NETs comprise 89% of small bowel NETs and often cause symptoms, though they may be found incidentally during routine screening colonoscopy when the terminal ileum is carefully examined. [2-4] Reports have shown that ileal NETs, even when smaller than 1 cm, can involve regional lymph nodes. [5] Speculating possible benefit from earlier discovery of ileal NETs, our aim was to compare tumor characteristics and patient survival when discovered during screening colonoscopy vs diagnostic colonoscopy.

We identified 28 patients with ileal NET found during colonoscopy between 2005 and 2021. Mean patient age at diagnosis was 60. All patients underwent surgical resection. Table 1 illustrates demographic and tumor-related details for the 15 patients who were asymptomatic and having colon cancer screening or surveillance. Table 2 details the remaining 13 patients who were having diagnostic evaluation of symptoms, abnormal computed tomography or abnormal stool testing. Tumor size ranged from 0.5 to 3.7 cm (mean 1.8 cm). Lymph nodes were involved in 25 of 28 patients (89%). In 3 patients without lymph node involvement, tumors were small (0.5, 0.5, 0.6 cm). The smallest tumor that was associated with nodal metastasis was 0.8 cm. At diagnosis, two patients had distant metastases. One had carcinoid syndrome and died from tumor complications 42 months later. The other remains alive at 84 months after diagnosis. One patient with T2N1 staging at diagnosis eventually died from an unrelated cause at 99 months. Another patient with nodal involvement at diagnosis developed liver metastases 8 years later and remains stable on treatment. Mean survival-to-date was nearly identical in screening and diagnostic groups (85 vs 88 months).

Our analysis of 28 cases of ileal NET discovered during screening and diagnostic colonoscopy allowed several observations. First, there were no obvious differences in tumor size or survival when tumors were found during either colonoscopy indication, suggesting that even patients with small tumors often present with gastrointestinal symptoms or abnormal testing that drives a need for diagnostic colonoscopy. Second, ileal NETs were frequently found in patients who had a preceding colonoscopy. That ileal intubation was performed on the preceding exam in only 57% suggests that careful ileal exam should be performed during screening and diagnostic colonoscopy whenever possible. The favorable diagnostic yield of this maneuver has been promoted previously in a large cohort. [6] Lastly, although nearly all patients with ileal NET had lymph node metastasis, disease-free survival was excellent in these patients. Similar observations were reported by others detailing ileal NETs found during screening colonoscopy. [7-9] The largest series published to date by Zakaria et al described 9 patients, 7 of whom had either nodal (6) or distant (1) metastasis. Follow-up data was available in 7 of 9 and all were disease-free at 1-4 years. [7] Ten Cate et al detailed 5 patients – all had nodal metastases and remained disease free at 1.5-12.5 years after surgery. [9]

We conclude that tumor characteristics and survival rates for ileal NETs are no different when diagnosed during asymptomatic screening colonoscopy or diagnostically indicated colonoscopy. Although nearly all patients had nodal metastasis at time of diagnosis, prognosis in these patients was excellent. Finally, the findings of our report corroborate conclusions from others that routine ileal intubation adds diagnostic value and should be attempted during screening and diagnostic colonoscopy.

Disclosure of Financial Interests:

Both authors declare that they have no relevant financial interests to disclose.

Funding:

Both authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Author Contributions:

Kaden Narayani participated in the design and development of the protocol/project, submitted the protocol for IRB review, performed data collection and analysis, and participated in manuscript writing and review.

Raj Narayani participated in the design and development of the protocol/project, audited the dataset, refined the data analysis, participated in manuscript writing and review, and submitted the manuscript.

Statement of Compliance with Ethical Standards:

The design and protocol for this study was reviewed by Covenant Health Institutional Review Board and approved for exemption based on criteria under 45 CFR 46.10(b)(4). None of the research performed during the study involved human participants and/or animals. Only historically obtained, unidentifiable human subject data was reviewed in compliance with and after proper review by noted national institutional review board.

Bilimoria KY, Bentrem DJ, Wayne JD, Ko CY, Bennett CL, Talamonti MS. Small bowel cancer in the United States: changes in epidemiology, treatment, and survival over the last 20 years. Ann Surg 2009; 249:63-71. https://doi.org/10.1097/SLA.0b013e31818e4641.
Ahmed M. Gastrointestinal neuroendocrine tumors in 2020. World J Gastrointest Oncol 2020; 12(8):791-807. https://doi.org/10.4251/wjgo.v12.i8.791.
Rorstad O. Prognostic Indicators for Carcinoid Neuroendocrine Tumors of the Gastrointestinal Tract. J Surg Oncol 2005; 89:151–160. https://doi.org/10.1002/jso.20179
Yoon JY, Kumta NA, Kim MK. The Role of Endoscopy in Small Bowel Neuroendocrine Tumors. Clin Endosc 2021; 54(6):818-824. https://doi.org/10.5946/ce.2020.296
Walsh JC, Schaeffer DF, Kirsch R, Pollett A, Manzoni M, Riddell RH, Albarello L. Ileal "carcinoid" tumors-small size belies deadly intent: high rate of nodal metastasis in tumors ≤1 cm in size. Hum Pathol 2016; 56:123-127. https://doi.org/10.1016/j.humpath.2016.05.023
Jeong SH, Lee KJ, Kim YB. Diagnostic value of terminal ileum intubation during colonoscopy. J Gastroenterol Hepatol 2008; 23(1):51-55. https://doi.org/10.1111/j.1440-1746.2007.05151.x
Zakaria A, Alnimer L, Byrd G, Piper M, Raphael M, Warren B, Piper M. Asymptomatic Ileal Neuroendocrine "Carcinoid" Tumor Incidentally Diagnosed on Colorectal Cancer Screening Colonoscopy: Does Routine TI Intubation Matter? Case Rep Gastrointest Med 2021;6620036. https://doi.org10.1155/2021/6620036
Yarze JC, et al. Detection of Asymptomatic Ileal Carcinoid Tumors During Ileal Intubation at Screening Colonoscopy: A Case Series. Am J Gastroenterol 2009; 104:3114-15. https://doi.org/10.1038/ajg.2009.472
Ten Cate EM, et al. Post-surgical Surveillance of Locally Advanced Ileal Carcinoids Found by Routine Ileal Intubation During Screening Colonoscopy: A Case Series. J Med Case Rep 2014; 8:444-46. https://doi.org/10.1186/1752-1947-8-444

Table 1 Ileal NET cases identified during screening/surveillance colonoscopy

Patient	Age	Colonoscopy indication	Prior colonoscopy (ago)	Ileum seen?	Tumor Size (cm)	Stage	Survival (months)	Deceased?	CgA
1	74	screening	Y (10 years)	NA	1.0	T2N1	70	N	normal
2	66	screening	N	NA	3.7	T3N1	108	N	normal
3	67	screening	N	NA	2.5	T3N1	115	N	498
4	52	screening	N	NA	2.0	T2N1*	117	N	NA
5	72	screening	N	NA	1.5	T2N1	88	N	108
6	56	screening	N	NA	2.3	T2N1	49	N	119
7	82	surveillance	N	NA	1.0	T2N1	211	N	NA
8	53	surveillance	Y (2 years)	N	2.8	T3N1	103	N	129
9	69	surveillance	Y (5 years)	N	0.5	T1N0	98	N	normal
10	76	surveillance	Y (9 years)	N	1.0	T2N1	56	N	NA
11	71	surveillance	Y (6 years)	N	1.4	T3N1	50	N	NA
12	58	surveillance	Y (7 years)	Y	1.5	T3N1	63	N	NA
13	77	surveillance	N	NA	0.9	T2N1	43	N	normal
14	55	screening	Y (5 years)	N	1.1	T2N1	19	N	normal
15	66	surveillance	Y (5 years)	Y	1.8	TxNxM1	84	N	41

*patient developed metastases 8 years after original diagnosis; CgA: chromogranin A value; NA: not available

Table 2 Ileal NET cases identified during diagnostic colonoscopy

Patient	Age	Colonoscopy indication	Prior colonoscopy (ago)	Ileum seen?	Tumor Size (cm)	Stage	Survival (months)	Deceased?	CgA
1	60	abnormal CT findings	Y (3 years)	Y	3.5	TxNxM1	42	Y	225
2	46	GI bleeding	N	NA	1.6	T2N1	111	N	normal
3	48	abnormal CT findings	Y (9 months)	Y	0.8	T2N1	166	N	normal
4	46	abdominal pain/altered bowel habit	N	NA	0.6	T1N0	185	N	NA
5	58	abnormal CT findings	Y (4 years)	N	2.0	T2N1	99	Y	NA
6	61	positive mt-sDNA	N	NA	2.5	T3N1	48	N	68
7	59	positive FIT	Y (5 years)	N	1.5	T2N1	186	N	NA
8	65	positive FIT	Y (3 years)	N	2.0	T1N1	77	N	1002
9	48	abdominal pain/GI bleeding	N	NA	1.5	T3N1	52	N	1119
10	48	GI bleeding	N	NA	3.5	T3N1	53	N	NA
11	68	altered bowel habit	N	NA	0.5	T1N0	41	N	491
12	50	diarrhea; Crohn ileitis	Y (2 years)	Y	2.5	T3N1	20	N	normal
13	41	diarrhea/GI bleeding	N	NA	2.5	T3N1	35	N	NA

CT: computed tomography scan; GI: gastrointestinal; FIT: fecal immunochemical test; mt-sDNA: multi-target stool DNA test; CgA: chromogranin A value; NA: not available

No competing interests reported.

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Journal Publication

published 26 Dec, 2022

Read the published version in Journal of Gastrointestinal Cancer →

Editorial decision: Major revision
08 Dec, 2022
Reviews received at journal
06 Dec, 2022
Reviewers agreed at journal
09 Oct, 2022
Reviewers invited by journal
24 Sep, 2022
Editor assigned by journal
24 Sep, 2022
Submission checks completed at journal
23 Sep, 2022
First submitted to journal
20 Sep, 2022

You are reading this latest preprint version

Ileal neuroendocrine tumors detected during screening or diagnostic colonoscopy – case series and comparison of tumor characteristics.

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