How many serial sections are needed to detect apoptosis in endoscopic biopsies with gastrointestinal graft versus host disease?

Wong, Newton A C S; Marks, David I.

doi:10.1136/jclinpath-2019-206310

Cited by 5 publications

(5 citation statements)

References 11 publications

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“…We found that higher maximum histological grades under any system correlated strongest with steroid therapy. However, we could not establish a histological cut-off to differentiate clinically insignificant aGvHD from significant counterparts by quantifying apoptotic bodies [ 14 , 21 ], even though the apoptotic body counts correlated with the application of steroid therapy. An increase in apoptotic bodies was observed in patients without clinically apparent intestinal aGvHD who had macroscopically bland mucosa; this is consistent with our previously published data [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…First, there are competing diagnostic and grading systems for colon aGvHD, with the Lerner [ 11 ], Sale [ 12 ], and Melson [ 13 ] methods being the most popular; to date, these have not been compared with respect to their diagnostic accuracy and prognostic impact. Second, previous analyses are generally based on a single biopsy per patient only [ 6 , 7 , 14 ]; this disregards the variations in aGvHD manifestations throughout the colon, which are profound [ 8 – 10 , 15 ]. Thus, evaluating multiple biopsy sites per patient using the most appropriate diagnostic system would greatly enhance the histological assessment of aGvHD, thereby guiding both patient management as well as further scientific exploration.…”

Section: Introductionmentioning

confidence: 99%

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An investigation of the diagnostic, predictive, and prognostic impacts of three colonic biopsy grading systems for acute graft versus host disease

et al. 2021

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Acute graft versus host disease (aGvHD) is an important, life-threatening complication after allogeneic hematopoietic stem cell transplantation (alloHSCT). To investigate the value of multiple simultaneous colon biopsies in improving diagnostic accuracy in patients with aGvHD, we retrospectively analyzed 157 patients after alloHSCT. The biopsies were evaluated individually using three established histological grading systems (Lerner, Sale, and Melson). The maximum, minimum, median, and mean histological aGvHD grades were calculated for each patient, and the results were correlated with the Glucksberg grade of clinical manifestation of GvHD, steroid therapy status, and outcome. We found that multiple colon biopsies enhanced diagnostic sensitivity. Moreover, higher histological grades correlated with steroid therapy initiation and refractoriness; the latter particularly occurred when advanced damage was present in all samples and healthy colon mucosa was reduced or absent. On multivariate analysis, the minimal Lerner and Glucksberg grades for intestinal aGvHD were significantly associated with steroid treatment failure. Ninety-nine patients died. The median survival was 285 days after the biopsies were taken. Fifteen patients died from relapse of their underling disorder and 84 from other causes, mostly infection (53 patients) and GvHD (14 patients). Multivariate analysis revealed a significant association between none-relapse mortality and the mean Lerner grade, minimum Melson grade, Glucksberg organ stage, and platelet counts. Thus, we found the Lerner system to be superior to the other grading methods in most instances and histologic evaluation of multiple simultaneously obtained biopsies from the colon to result in a higher diagnostic yield, which helps plan systemic steroid treatment while predicting treatment response and outcome.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

An investigation of the diagnostic, predictive, and prognostic impacts of three colonic biopsy grading systems for acute graft versus host disease

et al. 2021

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“…The presence of granulomas was also assessed in all GI biopsies from two retrospective cohorts of haematopoietic transplant patients: (i) patients with clinically and histologically validated GI GVHD from another study 7 ; and (ii) all patients who had received UCB at the BMTU over a 7-year period.…”

Section: Methodsmentioning

confidence: 99%

The diagnostic and clinical significance of granulomas in gastrointestinal biopsies from haematopoietic transplant patients

Wong

Marks²

2021

Histopathology

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Aims The diagnostic and clinical significance of granulomas in gastrointestinal (GI) biopsies from haematopoietic transplant patients remains disputed, especially following the proposal of cord colitis syndrome (CCS) as a new entity. The aim of the following study was to explore this controversy by identifying such biopsies with granulomas and detailing their clinicopathological associations. Methods and results Twelve patients with granuloma‐containing biopsies were identified from across three scenarios: prospectively during a GI pathologist’s routine practice over a period of 5 years; retrospectively from a cohort of transplant patients with clinically validated GI graft versus host disease (GVHD); and retrospectively from a cohort of patients who had received umbilical cord blood (UCB). Their clinicopathological assessments (which included unique long‐term patient follow‐up) showed that granulomas are only rarely seen across all GI biopsies from haematopoietic transplant patients, and may uncommonly constitute a histological feature of GI GVHD. Granulomas—and especially well‐defined, non‐cryptolytic ones—are more commonly present in GI biopsies from UCB recipients, but do not show any accompanying histological features that are different from those seen in granuloma‐containing biopsies from other patient groups. Furthermore, the three UCB recipients with granuloma‐containing biopsies were clinically diagnosed with GVHD rather than CCS. Finally, polymorphic post‐transplant lymphoproliferative disorder (PTLD) can present histologically as GI granulomatous inflammation that mimics Crohn’s disease. Conclusions Granulomas in GI biopsies of haematopoietic transplant patients may often indicate a treatable aetiology such as GVHD or PTLD. Granulomas are more commonly seen in GI biopsies from UCB recipients, but do not necessarily indicate a diagnosis of CCS.

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“…In the current research, we have already seen the potential of MSC-ApoVs in disease regulation, tissue regeneration, and drug delivery. There are other roles for ApoVs, such as disease diagnosis [82][83][84] and vaccine development. [51] More functions and applications for MSC-ApoVs are yet to be discovered by researchers.…”

Section: Challenges and Perspectivesmentioning

confidence: 99%

Apoptotic Vesicles of MSCs: The Natural Therapeutic Agents and Bio‐Vehicles for Targeting Drug Delivery

Lin

Zhang

2023

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Mesenchymal stem cell (MSC)‐based therapies are increasingly recognized as promising cellular therapeutics and show the ability to treat various diseases. However, the underlying mechanism is not fully elucidated. Some recent studies have shown an unexpected result whereby MSCs undergo rapid apoptosis following administration but still exert therapeutic effects in some disease treatments. Such a therapeutic mechanism is believed to associate with the released apoptotic vesicles from apoptotic MSCs (MSC‐ApoVs). This finding inspires a novel therapeutic strategy for using MSC‐ApoVs for disease treatment. The present review aims to summarize the biogenesis, physiological functions, therapeutic potentials, and related mechanisms of apoptotic vesicles in MSC‐based therapy. In addition, the potential applications of MSC‐ApoVs as natural therapeutic agents and natural drug delivery vehicles are proposed and highlighted. The present review is hoped to provide a general understanding of MSC‐ApoVs in disease treatment and inspire potential applications in targeted drug delivery.

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How many serial sections are needed to detect apoptosis in endoscopic biopsies with gastrointestinal graft versus host disease?

Cited by 5 publications

References 11 publications

An investigation of the diagnostic, predictive, and prognostic impacts of three colonic biopsy grading systems for acute graft versus host disease

An investigation of the diagnostic, predictive, and prognostic impacts of three colonic biopsy grading systems for acute graft versus host disease

The diagnostic and clinical significance of granulomas in gastrointestinal biopsies from haematopoietic transplant patients

Apoptotic Vesicles of MSCs: The Natural Therapeutic Agents and Bio‐Vehicles for Targeting Drug Delivery

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