Mixed epithelial endocrine neoplasms of the colon and rectum – An evolution over time: A systematic review
Bibliographic record
Abstract
BACKGROUND: Mixed tumors of the colon and rectum, composed of a combination of epithelial and endocrine elements of benign and malignant potential are rare neoplasms. These can occur anywhere in the gastrointestinal tract and are often diagnosed incidentally. Though they have been a well-documented entity in the pancreas, where the exocrine-endocrine mixed tumors have been known for a while, recognition and accurate diagnosis of these tumors in the colon and rectum, to date, remains a challenge. This is further compounded by the different terminologies that have been attributed to these lesions over the years adding to increased confusion and misclassification. Therefore, dedicated literature reviews of these lesions in the colon and rectum are inconsistent and are predominantly limited to case reports and case series of limited case numbers. Though, most of these tumors are high grade and of advanced stage, intermediate and low grade lesions of these mixed tumors are also increasingly been reported. There are no established independent consensus based guidelines for the therapeutic patient management of these unique lesions. AIM: To provide a comprehensive targeted literature review of these complex mixed tumors in the colon and rectum that chronicles the evolution over time with summarization of historical perspectives of terminology and to further our understanding regarding their pathogenesis including genomic landscape, clinicoradiological features, pathology, treatment, prognosis, the current status of the management of the primary lesions, their recurrences and metastases. METHODS: A comprehensive review of the published English literature was conducted using the search engines PubMed, MEDLINE and GOOGLE scholar. The following search terms ["mixed tumors colon" OR mixed endocrine/neuroendocrine tumor/neoplasm/lesion colon OR adenocarcinoma and endocrine/neuroendocrine tumor colon OR mixed adenocarcinoma and endocrine/neuroendocrine carcinoma colon OR Amphicrine tumors OR Collision tumors] were used. Eligibility criteria were defined and all potential relevant items, including full articles and/or abstracts were independently reviewed, assessed and agreed upon items were selected for in-depth analysis. RESULTS: In total 237 full articles/abstracts documents were considered for eligibility of which 45 articles were illegible resulting in a total of 192 articles that were assessed for eligibility of which 139 have been selected for reference in this current review. This seminal manuscript is a one stop article that provides a detailed outlook on the evolution over time with summarization of historical perspectives, nomenclature, clinicoradiological features, pathology, treatment, prognosis and the current status of the management of both the primary lesions, their recurrences and metastases. Gaps in knowledge have also been identified and discussed. An important outcome of this manuscript is the justified proposal for a new, simple, clinically relevant, non-ambiguous terminology for these lesions to be referred to as mixed epithelial endocrine neoplasms (MEENs). CONCLUSION: MEEN of the colon and rectum are poorly understood rare entities that encompass an extensive range of heterogeneous tumors with a wide variety of combinations leading to tumors of high, intermediate or low grade malignant potential. This proposed new revised terminology of MEEN will solve the biggest hurdle of confusion and misclassification that plagues these rare unique colorectal neoplasms thus facilitating the future design of multi institutional prospective randomized controlled clinical trials to develop and evaluate newer therapeutic strategies that are recommended for continued improved understanding and personal optimization of clinical management of these unique colorectal neoplasms.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.005 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".