Clinical Case Summary

A middle-aged man underwent screening colonoscopy during which a diminutive (3–4 mm) polyp was removed by cold snare polypectomy. The procedure was uneventful. Within hours, he developed painless scrotal swelling. Examination revealed subcutaneous emphysema confined to the scrotum (scrotal crepitus) with a soft, non-tender abdomen. He remained afebrile with stable vital signs. Abdominal computed tomography (CT) demonstrated retroperitoneal free air tracking into the scrotum (pneumoscrotum) with no intraperitoneal free air or fluid. Despite the absence of peritoneal signs, the atypical location of free air prompted surgical consultation. An exploratory laparotomy was performed. Intraoperatively, no colonic perforation or contamination was identified, including at the polypectomy site. The air leak was presumed to stem from a sealed microperforation or mucosal defect that allowed retroperitoneal air dissection. The patient had an uneventful recovery and was discharged on postoperative day five. Pneumoscrotum is a rare but recognized complication of colonoscopy, usually resulting from retroperitoneal air dissection without overt perforation (1–3). Most reported cases have been managed conservatively; however, when air dissects into atypical anatomical compartments or if clinical uncertainty exists, surgical exploration may be warranted to exclude a full-thickness injury (2,3). This case highlights the need for individualized management based on clinical and radiological findings, and underscores a rare complication of a routine colonoscopic polypectomy.

References

1) Singh S, Thakur M. Pneumoscrotum after colonoscopy. Can J Gastroenterol. 2008;22(4):411–413.
— This case report describes an instance of pneumoscrotum following colonoscopic polypectomy, managed conservatively. It highlights air dissection from retroperitoneum into the scrotum and notes the rarity of the condition.

2) Graepler F, Lauer UM, Horger MS, et al. Pneumoscrotum after colonoscopic polypectomy. Endoscopy.2007;39(Suppl 1):E90.
— A rare case of post-polypectomy pneumoscrotum requiring laparotomy. No perforation was found intraoperatively, underscoring that extensive air can dissect without overt bowel rupture.

3) Fu KI, Sano Y, Kato S, et al. Pneumoscrotum: a rare manifestation of perforation associated with therapeutic colonoscopy. World J Gastroenterol. 2005;11(32):5061–5063.
— This article presents pneumoscrotum as a clinical manifestation of colonic microperforation and describes the potential retroperitoneal air pathway into the scrotum.

Introduction

Besides analgesia, opioids affect gastrointestinal (GI) motility, including decreased bowel peristalsis and delayed gastric emptying. Peripherally acting mu-opioid receptor antagonists, like naloxegol, are approved for treating opioid-induced constipation.

Aims & Methods

We aimed to evaluate the effects of naloxegol on opioid-induced lower GI tract dysfunction using magnetic resonance imaging (MRI) to assess changes in colonic volumes in healthy volunteers (HV).
In this double-blind, randomised, three-way crossover study, 15 HV complete three study visits, separated by ≥1 week washout, with administration of 25 mg naloxegol + 60 mg codeine, 60 mg codeine + placebo, or double placebo. During each visit, five abdominal MRI scans (each 20 min.) are obtained at 30 min intervals, at baseline, after drug intake, after a standardized 44 g oatmeal and 100 mL Nutridrink (313 kCal) meal, after a second drug dose, and after a bisacodyl 10 mg suppository administration. Colonic segmental volumes were quantified from all MRI scans using Entrolytics (Motilent, London, UK) in the ascending, transverse, descending, and rectosigmoid colon. We recorded the passage of stool during the study visit. Results are presented as medians with min. and max. P-values <0.05 are considered statistically significant. Adjusted p-values are used in case of post-hoc analysis.

Results

Interim analysis on 8 HVs (mean age 36±5y, 75% females) revealed that two subjects made stool on 2 mornings before the study visit. Four subjects passed stool in the double placebo group (2 postprandial, 2 post-bisacodyl), and 2 of them passed stool in the other 2 groups as well, around the same time. A significant scan x group effect was found for the whole colon volumes (p<0.05). More specifically, there was a significant difference in median ascending colon volumes between the scans (p=0.03), and especially in the double placebo group (Table). Although there was no significant difference in the median transverse colon volumes, bisacodyl led to a significant decrease in descending colon volume (p<0.0001), more specifically in the naloxegol+codein group and the double placebo group (ps<0.05), but not in the codein+placebo group. No significant differences in volumes of the rectosigmoid were detected.

Conclusion

Interim MRI analysis of 8 HVs suggests different colonic motility responses across groups and timepoints. Toilet visits were suppressed in both codeine groups. Different responses to drug and food intake were found in the ascending and descending colon between the naloxegol+codein and double placebo group on one hand compared to the codein+placebo group. Expansion and analysis of the full number of subjects will further clarify insights into the acute colonic responses to opioids and potential reversal by naloxegol.

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

Although traditionally regarded as a vestigial organ, the appendix is increasingly recognized for its potential role in modulating gut immunity and contributing to the development of significant inflammatory or neoplastic intestinal diseases [1]. However, the underlying mechanisms linking the appendix to these immune and pathological processes remain poorly understood. This study aimed to investigate the relationship between the local immune microenvironment and the mutational landscape of rectal carcinomas in the context of prior or progressive appendectomy status.

Aims & Methods

This study aimed to investigate the relationship between the local immune microenvironment and the mutational landscape of rectal carcinomas in the context of prior or progressive appendectomy status.
Patients enrolled in the IMMUNOREACT 1 and 2 studies (NCT04915326 and NCT04917263, respectively) were stratified according to appendectomy status. Immunohistochemical analysis was performed to assess a range of immune markers, including CD3, CD4, CD8, CD8β, Tbet, FoxP3, PD-L1, MSH6, PMS2, and CD80. Additionally, flow cytometry was employed to evaluate the percentage of epithelial cells expressing CD80, CD86, CD40, HLA-ABC, or HLA-DR, as well as to quantify activated CD8+ T cells, CD4+ Th1 cells, and regulatory T cells (Tregs). Non-parametric tests were used.

Results

In this cohort, 41 patients out of 163 underwent appendectomy for other causes (e.g. appendicitis) before having been diagnosed with a rectal cancer. When the two groups were compared for microenvironmental features, in the normal mucosa of patients who had a previous appendectomy there was a higher rate of epithelial cells expressing HLA-abc (p=0,04) and a higher expression of CTLA4 on CD3+ T cells (p=0,03) when compared to appendectomy-naive patients. Within the rectal cancer tissue, a higher expression of CD86 on epithelial (cancer) cells expression was found in patients who already had an appendectomy (p=0,03). In therapy naïve patients, previous appendectomy was associated to a higher activation of CD4+ T helpers (expression of CD25), (p=0.04), and to tendency of higher rate of epithelial cells expressing HLA-abc (p=0,06) and of T cells expressing CTLA-4 (p=0.08). In patients who had neoadjuvant therapy, lower level of PD-L1 on the leukocyte surface were observed in patients who had a previous appendectomy (p=0.039).

Conclusion

Our findings suggest that prior appendectomy may be associated with distinct alterations in the local immune microenvironment of rectal carcinomas, including increased expression of antigen-presenting and immune-regulatory molecules such as HLA-BC, CTLA4, and CD86. In therapy naïve patients, appendectomy seem to increase the activation of T helper cells counterbalanced by an increase of the number of T cells expressing CTLA-4. These immune shifts in both tumour tissue and adjacent healthy mucosa support the hypothesis that the appendectomy may in somehow alter the interaction between epithelia cells and intraepithelial T cells. Further trancriptomic ​analysis will shed light on the effect of appendectomy on mucosal microevironment of ​rectal cancer patients.

References

1. Collard MK, Tourneur-Marsille J, Uzzan M, Albuquerque M, Roy M, Dumay A, Freund JN, Hugot JP, Guedj N, Treton X, Panis Y, Ogier-Denis E. The Appendix Orchestrates T-Cell Mediated Immunosurveillance in Colitis-Associated Cancer. Cell Mol Gastroenterol Hepatol. 2023;15(3):665-687.

Introduction

Ingestible sensors hold the promise to revolutionize the monitoring of gastrointestinal diseases, including inflammatory bowel disease (IBD). These miniature electronic capsules could provide a minimally-invasive, cost-effective, and patient-friendly alternative to traditional endoscopic procedures, with the promise of greatly enhancing disease tracking and management.

Aims & Methods

To enable real-time, minimally-invasive monitoring of gut health, we developed the Gastrointestinal Smart Module (GISMO), a highly miniaturized ingestible sensor (3 times smaller than video capsules) that measures redox balance, pH, and temperature throughout the GI tract.
Redox balance plays a key role in regulating the intestinal barrier and mediating interactions among the host, immune system, and gut microbiota. In conditions like IBD, gastrointestinal cancers, and irritable bowel syndrome (IBS), disruptions in immune response and shifts in the gut microbiome can destabilize the balance of oxidants and antioxidants^1,2. This imbalance leads to oxidative stress, detectable through altered redox signals.
After validation in both lab and pre-clinical models, the GISMO system was tested in healthy participants.

Results

In this first-in-human trial, 66 sensors were administered to 15 healthy participants. The GISMO system demonstrated feasibility, safety, and ease of use. Participants reported ease in swallowing the sensors and expressed willingness to ingest multiple capsules. No device-related adverse events occurred throughout the study. GISMO is the first device capable of measuring in vivo redox balance, providing high-resolution data every 20 seconds. The data revealed consistent profiles from an oxidative environment in the stomach to a strongly reducing environment in the colon. This group of self-reported healthy volunteers exhibited low inter- and intra-subject variability, providing a reliable baseline for future comparative studies in patient populations.

Conclusion

This trial marks the first in vivo measurement of redox balance along the human gut, paving the way for new insights into the role of redox balance in maintaining gut homeostasis, inflammation, and the gut microbiome. The ability to conduct frequent and simple monitoring could revolutionize the way gastrointestinal diseases are tracked and managed.

References

1. Campbell, E. L. & Colgan, S. P. Control and dysregulation of redox signalling in the gastrointestinal tract. Nat Rev Gastroenterol Hepatol 16, 106–120 (2019).
2. Bourgonje, A. R. et al. Oxidative Stress and Redox-Modulating Therapeutics in Inflammatory Bowel Disease. Trends Mol Med 26, 1034–1046 (2020).

Disclosure

AE, FL, NVH, RA have filed a patent application on sensing in the gastrointestinal tract with the European (EP4197437A1) and U.S. (US20230190178A1) patent office. FL, AE, and RS have filed a patent application on measuring and localizing inflammation in the gut (application no. EP 24217111.4) with the European patent office. TTo, IDCM, AE, FL have filed a patent application on localization of an ingestible device (application no. EP24222150.5).

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.

Introduction

This study aims to assess the impact of antithrombotic therapy on endoscopic findings in patients hospitalized for upper gastrointestinal bleeding.

Aims & Methods

We carried out a prospective, single-center cross-sectional study including 332 patients between June 2020 and February 2025. Patients were classified as antithrombotic (AT) users if they were receiving antiplatelet agents (such as low-dose aspirin or thienopyridines) and/or anticoagulants (including vitamin K antagonists, direct oral anticoagulants, or heparin).

Results

The mean age of the study population was 59 ± 16.7 years, with a marked male predominance (77.1%). Among them, 63 patients (19%) were receiving antithrombotic (AT) therapy—41 on antiplatelet agents and 39 on anticoagulants. Patients in the AT group were significantly older (68 vs. 57 years; p < 0.001) and had a higher burden of comorbidities (75.8% vs. 16.7%; p < 0.001). However, there were no significant differences between the AT and non-AT groups regarding the presence of active bleeding at endoscopy (12.7% vs. 16.8%; p = 0.425) or the need for endoscopic hemostasis (7.9% vs. 16%; p = 0.1).
In multivariate analysis, after adjustment for age, sex, comorbidities, active bleeding, and AT use, only the presence of active bleeding was independently associated with the need for endoscopic hemostasis. Specifically, active bleeding at endoscopy increased the odds of requiring hemostasis by 26-fold (OR: 26, 95% CI: 12.9–62.15; p < 0.001), whereas AT therapy was not an independent predictor (OR: 0.386, 95% CI: 0.105–1.42; p = 0.154).

Conclusion

In older patients receiving antithrombotic therapy and admitted for upper gastrointestinal bleeding, the risk of active bleeding during endoscopy and the need for endoscopic hemostasis do not appear to be increased.