Clinical Case Summary

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare aggressive non-Hodgkin lymphoma with poor prognosis. We present a case of colonic T-cell lymphoma diagnosed in a patient with refractory chronic diarrhoea.
A 60-year-old Chinese female with a family history of colon cancer had recurrent admissions with extensive workup for a 4-month history of chronic watery non-bloody diarrhoea and 12-kg weight loss. Initial blood tests showed normochromic normocytic anaemia and hypokalaemia. Stool studies were negative for infections but demonstrated elevated calprotectin and low elastase. Coeliac and autoimmune workup returned negative. A Computed Tomography scan showed prominent nonspecific central mesenteric abdominal nodes without pancreas or small bowel abnormalities.
Initial colonoscopy revealed a 2mm descending colon polyp and normal looking colonic mucosa. Random terminal ileum and colonic biopsies were unremarkable. Polyp histology showed focally increased intraepithelial lymphocytes insufficient to diagnose microscopic colitis.
Working differentials included pancreatic insufficiency, small intestinal bacterial overgrowth and irritable bowel syndrome. She was treated with various drugs including Rifaximin, Pancrelipase and Nortriptyline. However, her symptoms persisted with increasing stool calprotectin levels. A repeat colonoscopy performed 2 months after the initial endoscopy, showed normal colonic mucosa again. However, random colonic biopsies histology demonstrated florid intraepithelial lymphocytosis and immunohistochemistry stains confirming MEITL. Systemic chemotherapy was initiated and her diarrhoea resolved.
Though MEITL classically involves the small bowel, our case demonstrated florid colonic involvement. This patient’s indolent presentation illustrated the diagnostic pitfall of a normal looking colon during colonoscopy, raising the importance of random colonic biopsies and repeat evaluation in persistent unexplained diarrhoea.

References

Illustrative material: Endoscopic images showing normal-appearing colonic mucosa. Histological sections demonstrating intraepithelial lymphocytosis on initial colon biopsy. Subsequent biopsy on repeat colonoscopy with immunohistochemistry showing CD3, CD8, CD56, granzyme B, and TIA-1 positivity
References:
Ozaka S, Inoue K, Okajima T, et al. Monomorphic epitheliotropic intestinal T-cell lymphoma presenting as melena with long-term survival: A case report and review of literature. World J Gastroenterol. 2021;27(38):6501-6510. doi:10.3748/wjg.v27.i38.6501
Afzal A, Esmaeili A, Ibrahimi S, Farooque U, Gehrs B. Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma With Extraintestinal Areas of Peripheral T-Cell Lymphoma Involvement. Cureus. 2020;12(8):e10021. Published 2020 Aug 25. doi:10.7759/cureus.10021
Tian S, Xiao SY, Chen Q, Liu H, Ping J. Monomorphic epitheliotropic intestinal T-cell lymphoma may mimic intestinal inflammatory disorders. Int J Immunopathol Pharmacol. 2019;33:2058738419829387. doi:10.1177/2058738419829387
Shin SY. A Rare Case of Intestinal T-cell Lymphoma with Multiple Complications. JDCR 2023;11:114-118. doi.org/10.52927/jdcr.2023.11.2.114
Sun ZH, Zhou HM, Song GX, Zhou ZX, Bai L. Intestinal T-cell lymphomas: a retrospective analysis of 68 cases in China. World J Gastroenterol. 2014;20(1):296-302. doi:10.3748/wjg.v20.i1.296

Introduction

Irritable bowel syndrome (IBS) pathophysiology is multifactorial, with fermentable, oligo, di- and mono-saccharides and polyols (FODMAP) playing a role in symptom induction, presumably through osmotic effects and rapid colonic fermentation. While dietary studies assessed effects on symptoms, few have investigated the direct impact on colonic motility.

Aims & Methods

Using high-resolution colonic manometry (HRCM), we examined the effects of intracolonic fructose, fructans (fructo-oligosaccharides), or mannitol infusion on colonic motility in healthy volunteers (HV).
A double-blind three-way crossover study was conducted in 15 HVs, with a ≥ 2-week wash-out period between visits. After three days of a low FODMAP and low fiber diet, subjects came fasted to the hospital's endoscopy unit. They received a 250 mL water enema before advancing a 36-sensor solid state HRCM catheter with perfusion lumen into the ascending colon via colonoscopy under conscious sedation. After a 1 h recovery period, colonic pressures were recorded 1 h in the fasted state, for 20 min during infusion of FODMAP in the ascending colon (200 mL 290 mOsm/kg fructose, fructans, or mannitol), 2 h post-infusion, and 1 h postprandially after a standardized low-calorie meal. Colonic motor patterns were manually identified and compared between the three FODMAPs, with long ones ≥12 cm and high amplitude ones with at least 3 sensors ≥100 mmHg. Gastrointestinal symptoms were recorded every 15 minutes during the 4.5 h measurement. Results are presented as median with minimum and maximum ranges.

Results

Fifteen HV, 40% male (mean age 32 years (range 19-64 y), mean BMI 22.6 kg/m² (range 19.6-33.1)), completed the three study visits. Post FODMAP infusion, a significant difference in long anterograde patterns (p=0.04) was detected (Table). Postprandially, long synchronous (p=0.001) and long anterograde (LA) (p=0.0008) were more frequently observed with fructans, while mannitol tended to induce long retrograde patterns (p=0.07). Many of the long anterograde patterns were pan-colonic interrupted pressurizations (IP; previously described as related to gas transit; Leibbrandt J Clin Med 2023), and these were significantly more frequent after fructans infusion (p=0.004). High-amplitude retrograde-propagating contractions occurred 36 times in five HV: 50% after mannitol, 25% after fructans, and 25% after fructose infusion. There was no significant difference in gastrointestinal symptoms between the three FODMAPs, although flatulence and abdominal cramps were slightly increased after infusion of fructans.

Conclusion

Fructans and mannitol alter colonic motility patterns in distinct ways. Upon fructan infusion, there is a higher frequency of anterograde and synchronous activity, including interrupted pressurizations, which are suggested to be linked to gas transit. However, the frequency of these motor patterns was not altered by mannitol. These responses to different FODMAPs may contribute to symptom generation in IBS.

References

Van den Houte et al. Gastroenterology 2024
Leibbrandt J et al. Clin Med 2023

Introduction

Low mucosal impedance has been associated with reduced mucosal integrity and is measured during ambulatory pH/impedance monitoring, defined as mean nocturnal baseline impedance (MNBI)¹. More recently, techniques to measure impedance during endoscopy are emerging². In a prospective cohort of patients with EoE (SWALLeOeW Study, ISRCTN17786884, recruitment ongoing) we assessed the technicality of comparing mucosal impedance using MNBI with impedance measured during high-resolution impedance manometry (HRIM).

Aims & Methods

Here we aim to assess the practicability of obtaining mucosal impedance measurements during HRIM and to compare this with impedance measured using MNBI in a group of patients with EoE.
Prospective participants with EoE were assessed with HRIM and MNBI and this was repeated following a treatment period (Oro-dispersible Budesonide). The pooling of repeat measures from an individual participant was deemed to be appropriate in this evaluation as the purpose was to technically validate the process of comparing MNBI with HRIM, rather than to compare individual data points.
MNBI was calculated during a quiescent nocturnal period (Laborie, Ohmega) using the average of distal impedance channels 3 and 5 cm above the proximal border of the LOS¹. Impedance data was obtained during the supine resting period during HRIM and manually exported from the software (Medtronic). Extracted frames were at least 3 respiratory cycles and up to 30 seconds, and impedance was calculated based on the sensors 2.5 and 4.5, or 3.5 and 5.5 cm above the proximal border of the LOS, depending on catheter position.

Results

22 paired HRIM and MNBI measurements were obtained to date, from 15 participants. Reasons for unsuccessful MNBI measurements were not attempting test (n=2), non-tolerance (n=10), Nickel allergy (n=1), drop-out (n=2), or unable to intubate (n=1). Reasons for unsuccessful impedance measurement during HRIM were reflux during resting pressure measurement (n=1), catheter failure (n=3), drop-out (n=2), non-tolerance (n=8) or measurement not attempted (n=2).
The mean impedance values as measured by the two methods were not significantly different: mean MNBI (95% CI): 1570 (1210-1930) ohms, HRIM (95% CI) = 1330 (920-1740) ohms, p = 0.18. The mean difference between MNBI and HRIM was 245 ohms (1380-1870) (5-95^th percentiles).
Using a normality threshold of <1500 ohms³ being suggestive of impaired mucosal integrity, the majority (19/22) of the readings showed agreement between the two methods. Of the three that did not agree, MNBI suggested impaired mucosal integrity in one, and HRIM in the other two.

Conclusion

Measuring impedance during HRIM appears to be comparably practicable to MNBI measurement in patients with EoE, with the same numbers of successful measurements achieved by the two methods. Comparison of this preliminary data also indicates good agreement between methods. Impedance measurement during HRIM could provide a faster method of assessing mucosal integrity in EoE, whilst simultaneously assessing oesophageal motility. Further work in the SWALLeOeW study will correlate mucosal impedance findings with the Eosinophilic Oesophagitis Histology Scoring System⁴ and assess impedance change in response to treatment.

References

1. Hoshikawa, Y. et al. Measurement of Esophageal Nocturnal Baseline Impedance: A Simplified Method. J Neurogastroenterol Motil 26, 241–247 (2020).
2. Lei, W.-Y., Vaezi, M. F., Naik, R. D. & Chen, C.-L. Mucosal impedance testing: A new diagnostic testing in gastroesophageal reflux disease. Journal of the Formosan Medical Association 119, 1575–1580 (2020).
3. Sifrim, D. et al. Normal values and regional differences in oesophageal impedance-pH metrics: a consensus analysis of impedance-pH studies from around the world. Gut gutjnl-2020-322627 (2020).
4. Collins, M. H. et al. Newly developed and validated eosinophilic esophagitis histology scoring system and evidence that it outperforms peak eosinophil count for disease diagnosis and monitoring. Diseases of the Esophagus 30, (2016).

Introduction

The Atmo Capsule is a wireless motility capsule that senses and telemetrically transmits measurements of hydrogen (H₂) and carbon dioxide (CO₂) along the gut. In the colon, luminal concentrations of H₂ and CO₂ represent the metabolic activity of the microbial community. We hypothesized that delayed colonic transit would lead to altered gas profiles due to earlier depletion of fermentable substrates relative to transit time and/or facilitation of contact between methanogens and hydrogen (Levitt et al. CGH 2006).

Aims & Methods

The Atmo Capsule was administered to subjects with suspected upper and/or lower gut dysmotility. Colonic transit times (CTT) ≥ 59 h were considered delayed. Luminal H₂ and CO₂ concentrations (as time-normalized, area-under-the-curve [TN-AUC], [%.h]/h) were evaluated across the entire colon. Regional colonic profiles were evaluated per quartile of relative colonic transit, with quartiles 1 and 4 indicative of the proximal and distal colon, respectively. Gas measures were included if ≥ 50% of data were available for the corresponding segment. Fermentation profiles were estimated by the ratio of quartile 1:4 values, and time to peak concentrations were evaluated relative to CTT. Data were analyzed via Mann-Whitney test.

Results

The Atmo Capsule was administered to 209 subjects (median age 41; 188 female) with 170 yielding valid data on both colonic transit and colonic gas concentrations. Delayed colonic transit was identified in 60/170 (35%) subjects. In subjects with delayed CTT, H₂ concentrations tended to be higher in the proximal colon and lower in the distal colon with no overall difference across the region compared with those with normal transit (Table 1). CO₂ concentrations were higher throughout the colon except in the distal colon in subjects with delayed CTT. Peak concentrations of colonic H₂ and CO₂ were higher (H2, 8.7 h vs 5.9 %.h/h, p<0.01; CO2, 37.4 vs 29.9 %.h/h, p<0.01) and tended to occur earlier (H₂, 35.9 vs 47.0 % of colonic transit p=0.14; CO₂, 49.1 vs 86.8 % colonic transit, p<0.01) in patients with delayed compared with normal CTT.

Table 1. Gas profiles in patients with delayed colonic transit and correlation with symptom profiles. Data shown as median (interquartile range) and analyzed via Mann-Whitney test.

Conclusion

Colonic gas profiles, as measured via the Atmo Capsule, differed in patients with delayed compared with normal CTT, with patterns suggesting progressive depletion of fermentable substrates and/or conversion of H2 to methane during transit in those with delayed transit.

References

Levitt MD, Furne JK, Kuskowski M, Ruddy J. Stability of human methanogenic flora over 35 years and a review of insights obtained from breath methane measurements. Clin Gastroenterol Hepatol. 2006 Feb;4(2):123-9. doi: 10.1016/j.cgh.2005.11.006. PMID: 16469670.

Disclosure

These authors disclose the following: Braden Kuo, Anthony J. Lembo, Eammon M.M. Quigley, Satish S.C. Rao, and William D. Chey serve on the Medical Advisory Board of Atmo Biosciences. Michael Cline and Baharak Moshiree served on the Medical Advisory Board of Atmo Biosciences. Braden Kuo has received funding from NIH, Vanda, Atmo Biosciences, and Takeda and has consulted for Evoke, Takeda, Ironwood, Novo Nordisk, Cindome, and Neurogastrx. Thomas Abell has received funding from Gastric Dysrhythmias, Neurogastrx, NIH GpCRC, and Vanda and has consulted for Enterra Medical, Novo Nordisk, Nuvaira, and Vanda. Anthony J. Lembo has received funding from Ardelyx, Biomerica, GSK, Ironwood, Takeda, and Vibrant and holds stock with Allurion, Bristol Myer Squibb, and J&J. Abigail Stocker has received funding from Cindome, Enterra Medical, and Vanda. William D. Chey has received funding from Atmo Biosciences, Commonwealth Diagnostics Intl, QOL Medical, and Salix; has consulted for AbbVie, Ardelyx, Biomerica, Comvita, Gemelli, Ironwood, Nestle, QOL Medical, Phathom, Redhill, Salix, Vibrant, and Takeda; has filed patents with My Nutrition Health, Digital Manometry, and Rectal Expulsion Device; and holds stock options with Coprata, Evinature, Food Marble, Kiwi Bioscience, and Modify Health. The remaining authors disclose no conflicts.

Introduction

Emerging epidemiologic evidence suggested that moderate-to-vigorous physical activity (MVPA) was associated with a lower risk of steatotic liver disease (SLD).¹ However, several issues remain unanswered. First, prospective association between PA and hepatic steatosis was less investigated, with few studies mainly in Western populations,^{2, 3} but not in Chinese populations. Second, since sedentary behavior and PA are interrelated and may jointly affect the health outcomes,⁴ a key concern is whether moderate-to-vigorous physical activity (MVPA) can mitigate the detrimental link between sedentary time and SLD. Moreover, PA was shown to affect the gut microbiome by altering the bile acid profile and promoting the production of metabolites such as short-chain fatty acids^5,6 with benefit to SLD in animal models.⁷ However, PA-related gut microbes and metabolites, as well as their associations with SLD risk were rarely investigated at the population level.

Aims & Methods

We investigated the association between PA and the SLD risk in a cohort of 2,942 adults from the Anhui Liver Disease Study (ALDS), in which PA and SLD were measured using a validated self-reported questionnaire and transient elastography, respectively. In a subset of ALDS (n=330), we further identified gut microbial changes and serum metabolites related to MVPA assessed by accelerometer, and examined their associations with SLD risk. Fecal samples for 16S ribosomal RNA sequencing were collected twice (1-year apart) to evaluate 1-year microbial changes, targeted metabolomics analysis of baseline serum samples was performed using liquid chromatography tandem mass spectrometry, while PA was measured using a wrist-worn accelerometer for 3 consecutive days at baseline. Cox and Logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs) with 95%CIs, respectively.

Results

From 2020 to 2025, 565 SLD cases were newly diagnosed. MVPA levels were inversely (per 1-SD increase HR=0.91, 95%CI: 0.83–0.99) and sedentary hours were positively associated with the risk of SLD (HR=1.13, 95%CI: 1.03–1.24). Relative to long-low group (i.e., participants with long sedentary time and low MVPA level), HRs (95%CIs) for SLD risk were 1.00 (0.78–1.28), 0.93 (0.73–1.19), and 0.75 (0.58–0.97) for long-high, short-low, and short-high group, respectively. The α-diversity decreased in the low MVPA group (p=0.024) and the β-diversity changed in both low and high MVPA groups (all p=0.001). We identified 14 microbial genera whose relative abundance significantly changed in low or high MVPA group (all p_FDR<0.05). Among these genera, Proteus and Synergistes were associated with both low and high MVPA but in opposite directions, and were associated with SLD with ORs (95%CIs) of 1.15 (1.01–1.32) and 0.91 (0.78–1.06), respectively. Targeted metabolomics showed an inverse association between MVPA and serum L-Valine (β=-0.068, p_FDR=0.031), which was positively related to SLD risk (OR=16.40, 95%CI: 2.67–111.94). Significant correlations were also found between PA-associated microbial genera and L-Valine.

Conclusion

MVPA may modify gut microbial diversity and composition, as well as serum metabolite levels, and is associated with lower SLD risk, whereas sedentary behavior is associated with higher SLD risk.

References

[1] European Association for the Study of the Liver . Electronic address eee, European Association for the Study of D, European Association for the Study of O, et al. EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). J Hepatol 2024;81:492-542.
[2] McDonough DJ, Mathew M, Pope ZC, et al. Aerobic and Muscle-Strengthening Physical Activity, Television Viewing, and Nonalcoholic Fatty Liver Disease: The CARDIA Study. Journal of Clinical Medicine 2023;12.
[3] Liu M, Ye Z, Zhang Y, et al. Accelerometer-derived moderate-to-vigorous physical activity and incident nonalcoholic fatty liver disease. BMC Medicine 2024;22.
[4] Ekelund U, Tarp J, Steene-Johannessen J, et al. Dose-response associations between accelerometry measured physical activity and sedentary time and all cause mortality: systematic review and harmonised meta-analysis. Bmj 2019;366:l4570.
[5] Penney N, Barton W, Posma JM, et al. Investigating the Role of Diet and Exercise in Gut Microbe-Host Cometabolism. mSystems 2020;5.
[6] Campaniello D, Corbo MR, Sinigaglia M, et al. How Diet and Physical Activity Modulate Gut Microbiota: Evidence, and Perspectives. Nutrients 2022;14.
[7] Chen J, Vitetta L. Gut Microbiota Metabolites in NAFLD Pathogenesis and Therapeutic Implications. Int J Mol Sci 2020;21.

Introduction

Eosinophilic Esophagitis (EoE) is a clinicopathological disease that requires an integrated assessment combining clinical, endoscopic, and histological findings. Despite this, treatment decisions often remain symptom based. A treat-to-target strategy has recently been proposed to guide EoE management.

Aims & Methods

Retrospective single-center study of EoE patients followed between March 2012 and January 2024, with ≥12 months of follow-up. Clinical, endoscopic, histological data, and complications were assessed using the I-SEE score.

Results

A total of 82 patients with EoE were evaluated [75.6% (n=62) male, mean age 29 ± 13 years], with 37.8% (n=31) diagnosed during childhood. The most frequent symptom was food impaction (74.4%), and atypical symptoms were more common in pediatric patients (p=0.014). At baseline, 55.1% (n=43) presented with a fibrostenotic phenotype, more frequently in adults (p=0.012), and 32.9% (n=27) had moderate-to-severe disease based on the I-SEE score.
During follow-up, 56.1% (n=46) developed complications, most commonly food impaction requiring endoscopy. The presence of a fibrostenotic phenotype on initial endoscopy was a predictor of complications (OR 3.122; 95% CI 1.210–8.055; p=0.019). Both fibrostenotic phenotype (p=0.018) and moderate-to-severe I-SEE scores (p=0.004) were associated with increased need for therapeutic switching.
At 12 months, 50.0% (n=41) were asymptomatic; however, only 12.2% (n=10) had endoscopic healing and 9.8% (n=8) histologic remission. Throughout the study period, the rates of endoscopic and histologic healing remained below 25%.

Conclusion

The authors highlight the clinical dissociation of inflammatory activity and emphasize the importance of endoscopic and histologic healing to prevent disease progression.

References

Dellon, Evan S., et al. "A clinical severity index for eosinophilic esophagitis: development, consensus, and future directions." Journal of Allergy and Clinical Immunology 150.1 (2022): 33-47.