Letter to the Editor: Less can be more, rethinking colonic biopsy strategies for microscopic colitis in the era of green endoscopy

Abstract

In this issue recently published in the World Journal of Gastrointestinal Pharmacology and Therapeutics, Leung et al present data that challenge a long-standing recommendation in microscopic colitis (MC): Routine bilateral colonic biopsies. In a large cohort of treatment-naïve patients, right-sided biopsies demonstrated a diagnostic yield of 100%, whereas left-sided biopsies were less sensitive (92%) and never independently diagnostic in this cohort when right-sided samples were available. These findings invite reconsideration of established biopsy protocols, particularly in light of value-based care and green endoscopy principles. This article examines the evidentiary basis of current guidelines, explores the implications for efficiency and sustainability, and calls for evidence-guided refinement of MC biopsy recommendations.

Key Words: Microscopic colitis; Colon biopsy; Diagnostic yield; Guideline revision; Green endoscopy; Value-based care

Core Tip: Routine bilateral colonic biopsies for suspected microscopic colitis (MC) are rooted more in tradition than contemporary evidence. Emerging data suggest that right-sided colonic biopsies alone may be sufficient for diagnosis, without compromising accuracy. Reconsidering biopsy strategies offers an opportunity to maintain diagnostic rigor while reducing procedural burden, costs, and environmental impact-aligning MC diagnosis with principles of precision and sustainable gastroenterology.

TO THE EDITOR

Microscopic colitis (MC) occupies an uneasy intersection of certainty and doubt. Clinically, it is a well-established cause of chronic, non-bloody diarrhea. Histologically, it is definitive. Endoscopically, however, it is often indistinguishable from normal mucosa, compelling reliance on random biopsies for diagnosis.

From this uncertainty emerged a defensive strategy: Bilateral colonic sampling to guard against missed disease. Over time, this approach evolved from prudent caution into standardized recommendation, reinforced by international guidelines including those from the British Society of Gastroenterology (BSG) and other expert consensus groups advocating right- and left-sided biopsies in suspected MC. Importantly, contemporary international guidance-including the 2021 European guidelines and Spanish consensus statements-recommend obtaining at least 2–3 biopsies from both the right and left colon in suspected MC, reflecting a precautionary approach rooted in presumed patchiness. Yet dogma, once established, rarely interrogates itself. In this issue published in the World Journal of Gastrointestinal Pharmacology and Therapeutics, Leung et al[1] ask a question that guideline committees must now confront: Does routine bilateral sampling reflect contemporary evidence-or inherited precaution?

Patchiness revisited: Evidence over assumption

The rationale for bilateral biopsies stems from the long-standing concept of patchy histological distribution. While earlier histopathological literature suggested variability, contemporary data have been limited regarding segment-specific diagnostic yield.

Leung et al[1] provide quantitative clarity: Right-sided biopsy sets: 150/150 diagnostic (100%). Left-sided biopsy sets: 145/158 diagnostic (92%). Container-level yield: 98% (right) vs 91% (left). Paired sampling: 10% had positive right with negative left; none had positive left with negative right. Rectal yield: 75%. Critically, left-sided biopsies were never independently diagnostic in this cohort when right-sided biopsies were available. That qualifier matters. It prevents overgeneralization while preserving the force of the finding. The asymmetry is not subtle-it is systematic. If left-sided biopsies do not change diagnosis in paired analyses, are they contributing to diagnostic rigor-or perpetuating diagnostic ritual? The relatively lower diagnostic yield from rectal biopsies (75%) further reinforces the limitations of distal-only strategies. This finding aligns with American Society for Gastrointestinal Endoscopy standards and prior meta-analytic evidence supporting full colonoscopy over flexible sigmoidoscopy in the evaluation of chronic diarrhea when MC is suspected[2,3].

From defensive abundance to diagnostic precision

This study reframes the biopsy conversation from “How much is safe?” to “How much is sufficient?” Gastroenterology, like much of medicine, has historically favored abundance in the face of uncertainty. More biopsies feel safer. More containers feel thorough. Yet redundancy is not synonymous with rigor.

Through paired and container-level analyses, Leung et al[1] demonstrate that diagnostic certainty in MC may be achieved through targeted precision rather than maximal sampling. Their findings suggest that bilateral biopsy protocols may represent precautionary excess rather than evidence-based necessity. Importantly, this does not imply that bilateral sampling is wrong—only that its routine application may require recalibration.

Sustainability and value: From ethical ideal to measurable variable

Perhaps the most forward-looking dimension of this work is its integration of sustainability as a measurable outcome. The authors quantified histopathology processing time (mean 8 minutes 37 seconds per container) and estimated carbon impact, calculating that elimination of redundant left-sided containers across their study period could have saved the equivalent of approximately 1500 miles of car travel in emissions. These numbers are not symbolic-they are operational. In high-volume endoscopy units, small inefficiencies compound. If two diagnostic strategies yield equivalent outcomes, the one requiring fewer resources aligns more closely with value-based care and green endoscopy principles. Sustainability, in this framework, is not a constraint on quality. It is a dimension of quality.

Balancing enthusiasm with nuance

A persuasive argument must anticipate critique. Leung et al’s study[1] is retrospective and derived from a limited number of institutions. Sampling was not protocolized, and disease subtype distribution (lymphocytic vs collagenous colitis) may vary regionally[1].

Importantly, right-sided predominance was observed across both lymphocytic and collagenous colitis subtypes in this cohort, suggesting that the findings are not subtype-restricted; however, prospective multicenter validation is required to confirm generalizability across diverse populations and practice settings.

Furthermore, subtle endoscopic findings were not systematically incorporated into biopsy targeting strategies. Whether advanced imaging or directed sampling might further refine protocols warrants investigation. These limitations do not weaken the study’s central message. They contextualize it-and underscore the need for prospective evaluation rather than reflex dismissal.

Guidelines under the microscope

Guidelines shape not only practice, but professional norms. The BSG and other consensus bodies have appropriately emphasized that MC cannot be excluded without colonic biopsy. However, the specific requirement for bilateral sampling has rested on limited distributional evidence. Notably, current European (2021) and Spanish guidelines mandate obtaining multiple biopsies from both the right and left colon; however, the findings of Leung et al[1] challenge the necessity of routine left-sided sampling when right-sided biopsies are positive, raising important questions regarding the proportionality of existing recommendations[4,5]. The present data meet a reasonable threshold for guideline reassessment-not wholesale abandonment, but recalibration. Precaution is virtuous. Perpetual precaution without re-evaluation is not.

Policy-oriented call to action: Toward proportionate evolution

Guideline committees now face an opportunity to model evidence-responsive leadership. At minimum, the findings of Leung et al[1] justify: Re-evaluating the routine requirement for left-sided biopsies in suspected MC. Recognizing right-colon-focused sampling as a potentially sufficient diagnostic standard. Acknowledging evidentiary gaps underpinning bilateral biopsy recommendations. Integrating efficiency and sustainability metrics into future guideline frameworks. Encouraging prospective, multicenter validation studies. Guideline evolution need not be abrupt-but it must be responsive.

The question is no longer whether right-sided biopsies can diagnose MC-they demonstrably can. The question is whether our policies will adapt accordingly. If medicine is to embrace value-based care and green endoscopy not as slogans but as standards, biopsy protocols for MC represent a pragmatic and immediately actionable starting point.

Looking forward

This article does not call for conformity. It calls for reconsideration. Leung et al[1] have supplied the data. The responsibility now lies with the field-to debate, validate, and, if warranted, recalibrate. When evidence challenges dogma, progress depends not on defensiveness, but on disciplined reflection. The question has been asked. It deserves an answer.