Evidence map›Paper›PMID 36936198›Full record

ArticleTherapeutic advances in medical oncology2023

Diagnostic value of whole-mount crypt analysis of ileal biopsy specimens for the patients with familial small intestinal neuroendocrine tumors.

Yoshitatsu Sei, Joanne Forbes, Ben Da, Ehsan Chitsaz, Jianying Feng, Xilin Zhao, Marybeth S Hughes, Stephen A Wank

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Therapeutic advances in medical oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.4field-weighted citation impact, top 36% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 2 citations in OpenAlex.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Yoshitatsu SeiDigestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID https://orcid.org/0000-0002-3073-5126
Joanne ForbesDigestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Ben DaDigestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Ehsan ChitsazDigestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Jianying FengDigestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Xilin ZhaoDigestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Marybeth S HughesSurgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Stephen A WankChief, Gastroenterology Section, Digestive Disease Branch, National Institute of Diabetes, Digestive & Kidney Diseases, 10 Center Drive, Bldg 10, Rm 9C-101, MSC1804, Bethesda, MD 20892-1385, USA.
National Institutes of Health · USNational Institute of Diabetes and Digestive and Kidney Diseases · US

Funding

Natural History of Familial Carcinoid TumorZIADK071010 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI WANK, STEPHEN · 2009 to 2025
$13.6M
6 · The paper itself

Abstract

Background and Aims: Early-stage small intestinal neuroendocrine tumors (SI-NETs) are generally asymptomatic and difficult to diagnose. As a result, patients often present with late-stage incurable disease. SI-NETs originate from enterochromaffin (EC) cells, which develop enteroendocrine cell (EEC) clusters consisting of a subset of EC cells at the crypt bottom at an early stage of tumor progression. In a familial form of SI-NET, EEC clusters arise in a multifocal and polyclonal fashion. We sought to determine whether early detection and analysis of cryptal EEC clusters could provide insight into the development of SI-NETs and allow successful pre-symptomatic screening for at risk family members of patients with SI-NETs. Methods: Isolated crypts from endoscopic ileal biopsies or surgically removed specimens from 43 patients with familial SI-NET and 20 controls were formalin-fixed, immunostained for chromogranin A, and examined by confocal three-dimensional analysis for the presence of EEC cluster formations. Results: Examination of multiple areas of macroscopic tumor-free mucosa in surgically resected specimens from patients with familial SI-NET revealed widely distributed, independent, multifocal EEC micro-tumor formations of varying sizes. Consistent with this finding, randomly sampled ileal biopsy specimens identified aberrant crypt containing endocrine cell clusters (ACECs) in patients. ACECs were found exclusively in patients (23/43, 53%) and not in controls (0/20). Furthermore, analysis of positions and numbers of EECs in crypts and ACECs indicated significant increases in EECs at the crypt bottom, predominantly at positions 0 and 1' ( Conclusion: This study indicates that SI-NETs develop from deep crypt EC cells to become ACECs, micro-tumors, and ultimately gross tumors. This process occurs widely throughout the distal small intestine in patients with familial SI-NETs consistent with but not exclusively explained by germline disease. Finally, analysis of crypts from ileal biopsies could contribute in part to earlier diagnostic screening processes avoiding late-stage presentation of incurable disease.

Indexed as

biopsycarcinoidcryptenterochromaffinfamilialilealmultifocalneuroendocrine

Identifiers

PMID36936198
PMCPMC10014972
OpenAlexW4324123410

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.