Proximal-To-Distal Gradient and Its Implications in Differentiation and Prognosis in Colorectal Neuroendocrine...

Area of Science:

• Gastroenterology
• Oncology
• Developmental Biology

Background:

• Colorectal neuroendocrine neoplasms (CR-NENs) are traditionally classified as midgut or hindgut derivatives.
• This binary classification may oversimplify the complex developmental continuum of these tumors.
• Investigating a proximal-to-distal gradient is crucial for optimal stratification.

Purpose of the Study:

• To determine if CR-NEN phenotype and prognosis follow a continuous proximal-to-distal gradient.
• To identify the optimal stratification strategy for CR-NENs.
• To compare continuous spatial modeling with traditional categorical approaches.

Main Methods:

• Analysis of 1,158 patients from the RGETNE registry.
• Modeling anatomical location as a continuous variable using restricted cubic splines.
• Comparing prognostic performance using Akaike Information Criterion (AIC).

Main Results:

• A distinct proximal-to-distal gradient was observed in CR-NENs.
• Continuous modeling showed superior fit for Ki-67, outperforming categorical methods.
• Anatomical position was an independent prognostic factor, with increased risk distally.
• The midgut-hindgut dichotomy provided the most efficient statistical fit for predicting recurrence.

Conclusions:

• CR-NENs exhibit a topographical biological continuum.
• Continuous modeling is optimal for molecular research and assessing tumor aggressiveness.
• Traditional discrete classifications (midgut-hindgut or anatomical segments) remain most robust for clinical risk stratification and trial design.