Clinical Case Summary

The gastrointestinal tract is the most common site for primary extranodal non-Hodgkin lymphoma (NHL), with small intestinal and ileocecal NHL accounting for 8.6% and 7.0%, respectively. However, primary ileal diffuse large B-cell lymphoma (DLBCL) presenting as a submucosal tumor (SMT)-like lesion is exceedingly rare. We report a case of primary ileal DLBCL resected via endoscopic mucosal resection (EMR).
A 67-year-old woman presented with intermittent left abdominal pain for six days. Initial abdominal CT suggested partial intestinal obstruction and eccentric thickening of the terminal ileum, with enlarged adjacent lymph nodes. Colonoscopy revealed an SMT-like lesion in the terminal ileum with smooth surface mucosa, measuring approximately 10 × 10 mm. Endoscopic ultrasound (EUS) showed a hypoechoic lesion originating from the muscularis mucosae. After obtaining informed consent from the patient and her family, endoscopic EMR was performed. Histopathology revealed a small round cell tumor, raising suspicion of lymphoma. Immunohistochemistry confirmed the diagnosis of B-cell non-Hodgkin lymphoma. Molecular testing showed no BCL2 or C-MYC rearrangement, leading to a final diagnosis of non-germinal center B-cell-like (non-GCB) DLBCL. Bone marrow biopsy demonstrated normal marrow without infiltration. PET-CT confirmed localized disease, and the patient received R-CHOP chemotherapy.
Primary ileal DLBCL presenting as an SMT-like lesion is extremely rare, and accurate diagnosis is challenging with current endoscopic techniques such as EUS and magnifying endoscopy with narrow-band imaging. Endoscopic resection can be employed for both diagnostic and therapeutic purposes. In this case, timely detection, rapid intervention, definitive diagnosis, and effective multidisciplinary collaboration (involving imaging, endoscopy, pathology, and chemotherapy) provided the patient with optimal treatment, resulting in a favorable prognosis.

Introduction

Gastric emptying is controlled by phasic gastric contractions which occur at a frequency of ~3 cycles per minute (cpm) in phase with gastric slow waves. Tests to measure slow waves cannot directly detect abnormal contractions. The Atmo Capsule possesses an accelerometer that measures changes in capsule orientation and can thus detect gastric contractions. We analyzed accelerometer data to define its capability to characterize gastric contraction frequency and amplitude in patients with suspected dysmotility, and to assess if frequency or amplitude vary in relation to transit delay.

Aims & Methods

Gut transit was measured by the Atmo Capsule in 209 subjects: 48 with predominant upper GI (UGI) symptoms alone (suspected gastroparesis), 21 with lower GI (LGI) symptoms (suspected slow colon transit) alone, and 140 with combined UGI+LGI symptoms. This analysis utilized data from subjects recording valid gastric emptying time (GET) measures and did not incur protocol deviations affecting gastric transit. Delays in GET were categorized as: normal, <5 h; delayed, 5-10 h; severely delayed, ≥10 h. Fast Fourier Transformation (FFT) of the accelerometer data allows for the identification and analysis of the dominant gastric frequency and amplitude using 10-minute windows and a cutoff frequency of 4.5 cpm. Variability of frequency and amplitude measures were estimated by calculating interquartile range (IQR) and range (max-min) values and were analyzed in relation to presenting symptoms and gastric emptying delays.

Results

Gastric data from 190 subjects were suitable for analysis: gastric contractions with dominant frequencies of 3.30 cpm (IQR 0.47, range 1.47) and amplitudes of 0.10 arbitrary units (au) (IQR 0.04, range 0.14) were detected in 185 (97%) of subjects. Mean contraction frequency tended to be higher in those with delayed GET compared with no delay (p=0.016) and severe delay (p=0.005) (Table 1). Frequency IQR (p=0.002) and range (p=0.002) were higher for GET delay vs. no delay, while range was higher in severe GET delay vs no delay (p<0.001). Mean amplitude was higher in subjects with severe GET delay compared with normal delay (p=0.008) and normal transit (p=0.001). Amplitude IQR and range were both higher in those with severe GET delay compared with normal delay (p=0.002; p=0.001) and no delay (p<0.001 for both). Frequency metrics were similar irrespective of predominant symptoms. Amplitude means (p=0.022), IQR (p=0.030) and range (p=0.0004) were higher for UGI vs. LGI symptoms.

Table 1. Dominant gastric frequencies and amplitudes in relation to gastric emptying delays. Data shown as median (interquartile range) and analyzed via Kruskal-Wallis test.

Conclusion

The Atmo Capsule accelerometer reliably characterizes 3 cpm gastric contraction frequency and amplitude in subjects with proposed delays in gut transit. Increased variabilities in contraction frequency and amplitude were defined in those with severely delayed gastric emptying and increased amplitude variability was found for predominant upper GI symptoms. We propose these higher variations identified by accelerometry may reflect hypomotility or contractile dropout, suggesting additional clinical utility of the Atmo Capsule in suspected gastroparesis.

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

A large proportion of Inflammatory Bowel Disease (IBD) patients also develop liver diseases, predominantly primary sclerosing cholangitis (PSC), and more than 80% of PSC patients also have IBD. Coexistence of both diseases in patients, increase of five times the risk of developing a colorectal cancer, and causes liver transplantation failure. Both of IBD and PSC have no curative treatment yet, and the impact of IBD on liver homeostasis and reciprocally the impact of PSC on intestinal barrier (IB) remain largely unknown.

Aims & Methods

The aims of the study were to investigate the impact of (1) mouse models of IBD on liver homeostasis and (2) the impact of mouse models of PSC on IB integrity. Two models of colitis have been used. A model was conducted by adding 3% DSS in drinking water for five days, followed by two days of regular water. The second model of colitis was performed using a pre-sensitizing step involving subcutaneous injection of 2% oxazolone and five day later, a rectal injection of 1.5% oxazolone. As PSC mouse models, we used intra-peritoneal injection of 1µL/g mice weight of CCl₄ twice a week for 8 weeks and another model with a 0.1% diethyl 1,4-dihydro-2,4,6-trimethyl-3,5-pyridinedicarboxylate within diet for 3 weeks. Colitis and cholangitis severities were monitored by food consumption, macroscopic observations as well as calculation of Disease Activity Index which sum up scores of weight loss, bleeding and stool consistency. Fecal samples were tested for calprotectin and lipocalin by ELISA to estimate gut inflammation. Intestinal permeability (IP) was investigated in vivo by estimation of FITC-Dextran quantity in mice’s sera after oral administration and at mice sacrifice in ileum and colon tissues by measuring the flux of fluorescein sodium salt in Ussing chamber. To study liver homeostasis, we performed pathological analysis (H&E and Sirius red staining), and real-time PCR with a focus on fibrosis markers, bile acids metabolism and metabolic pathways.

Results

IBD models induced strong alteration of colonic homeostasis including increased fecal markers of inflammation (Calprotectin and Lipocalin-2) and tissues mRNA expression of inflammatory cytokines (Ifng…). These models of colitis were also accompanied by elevated IP and impaired liver genes expression level of fibrosis (Col3a1) and fatty acids metabolism (Fasn…), as well as cholesterol and bile acids transporters (Abcb11…). This was found to be correlated with impaired enterohepatic circulation of bile acids in the gut. Furthermore, an increase expression of mRNA markers of inflammation (Cxcl1…) was only observed in the liver of the DSS colitis model. However, no alteration of liver homeostasis, including infiltrated immune cells or fibrosis was revealed by histological analysis. PSC mouse models induced strong alterations of liver homeostasis and were associated with altered gut homeostasis shown by a strong increased IP.

Conclusion

Our data demonstrate that IBD colitis models impair liver homeostasis, while PSC models disrupt intestinal integrity. The data obtained from both IBD and PSC models demonstrated a significant increase in intestinal permeability, thereby underscoring it’s potential as an association between those diseases. Further investigations are ongoing in ours models as a next step will be to study a combination of both protocols to explore disease progression and severity.

References

Rabiee, Anahita, and Marina G Silveira. “Primary sclerosing cholangitis.” Translational gastroenterology and hepatology vol. 6 29. 5 Apr. 2021, doi:10.21037/tgh-20-266
Kim, You Sun et al. “Primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD): a condition exemplifying the crosstalk of the gut-liver axis.” Experimental & molecular medicine vol. 55,7 (2023): 1380-1387. doi:10.1038/s12276-023-01042-9

Introduction

Phase Angle (PA) represents a useful bioimpedance analysis-assessable marker of sarcopenia, accurately predicting liver-related hospitalizations in advanced chronic liver disease (ACLD), correlating with C-reactive protein levels. Clinically significant portal hypertension (CSPH) and systemic inflammation constitute the main hepatic decompensation drivers. A relevant proportion of Metabolic dysfunction-associated steatotic liver disease (MASLD) patients present sarcopenia (configuring the paradox of “sarcopenic obesity”), as well as compensated ACLD (cACLD)-MASLD individuals more rapidly progress to decompensation (dACLD) rather than other etiologies. However, the clinical applications of PA have never been specifically investigated in the setting of MASLD.

Aims & Methods

Considering the background, in MASLD, we primarily aimed to evaluate the trend of PA values across the different liver disease progression stages, investigating the relationship with the hepatic decompensation drivers; in dACLD-MASLD, we aimed to estimate the accuracy of the novel PA/C-reactive protein (CRP) index (PAC-I) in predicting 3-month further liver-related events (LREs)-determining hospitalizations.
In this observational study, between December 2023 and January 2025, MASLD patients were consecutively enrolled and stratified according to current LSM and eventual previous LREs in < F3 fibrosis (AF) (n.50), cACLD (n.50), and dACLD (n.50) patients. At baseline, anthropometrical, biochemical, nutritional, and clinical data [including the endoscopic assessment of CSPH and the relative severity (F1, F2, F3) of esophageal varices (OEVs)] were collected. Bioimpedance analysis was adopted to assess body composition parameters. Sarcopenia was diagnosed according to the European Working Group on Sarcopenia (EGWSOP2) criteria. MASLD-dACLD patients were followed up, and further acute decompensation (AD)-LREs-determining hospitalizations [severe ascites, severe hepatic encephalopathy (HE), OEV bleeding, and any acute bacterial infections] in the subsequent 3 months were recorded.

Results

In MASLD patients, PA (°) values inversely correlated with LSM [R: -0.711; p<0.0001], progressively decreasing according to the worsening of liver disease stages, emerging as statistically significantly lower in dACLD compared with cACLD individuals (p<0.0001). In dACLD patients, PA inversely correlated with CRP levels [R: -0.945; p:0.001]. Focusing on CSPH, PA values were significantly lower in > F2-OEV-affected individuals (p<0.0001). Multivariate analysis revealed CSPH (aHR 1.221, p<0.0001), CRP (aHR: 1.112, p:0.002), and PA (aHR: 1.178, p:0.003) as the variables significantly associated with 3-month further LREs’ occurrence in dACLD patients.
ROCy analysis revealed an elevated accuracy and superiority compared to PA alone (AUC PA:0.717; AUC PAC-I: 0.893; p:0.003) of PAC-I in predicting 3-month further LREs’ occurrence, identifying PAC-I < 2.35 as the best cut-off. Consistently, dACLD patients showing baseline PAC-I < 2.35 presented a higher risk [HR: 2.287, p: 0.032] of further LREs.

Conclusion

In MASLD, PA correlates with the main driver of progression, and the PAC-I represents a useful noninvasive tool in predicting short-term liver-related hospitalizations in dACLD patients.

References

1. Espirito Santo Silva DD, Waitzberg DL, Passos de Jesus R, Oliveira LPM, Torrinhas RS, Belarmino G. Phase angle as a marker for sarcopenia in cirrhosis. Clin Nutr ESPEN. 2019 Aug;32:56-60. doi: 10.1016/j.clnesp.2019.05.003. Epub 2019 May 31. PMID: 31221291.
2. Saueressig C, Glasenapp JH, Luft VC, Alves FD, Ferreira PK, Hammes TO, Dall'Alba V. Phase Angle Is an Independent Predictor of 6-Month Mortality in Patients With Decompensated Cirrhosis: A Prospective Cohort Study. Nutr Clin Pract. 2020 Dec;35(6):1061-1069. doi: 10.1002/ncp.10584. Epub 2020 Oct 15. PMID: 33058222.