Clinical Case Summary

A 69-year-old male presented with dysphagia, food regurgitation, weight loss, and halitosis with a 12-month evolution. An upper endoscopy revealed, at 32 cm from the dental arch, a large food bolus impacted in an area consistent with a large esophageal diverticulum (Figure 1), along with isolated esophageal contractions suggestive of tertiary contractions. A barium swallow study confirmed a distal esophageal diverticulum measuring 6x5 cm (Figure 2). Subsequently, a chest CT scan showed the diverticulum with a large amount of food content inside (Figure 3). High-resolution esophageal manometry (HRM) demonstrated a hypercontractile pattern of the esophageal body in more than 20% of swallows, consistent with a diagnosis of hypercontractile esophagus or Jackhammer esophagus (Figures 4 and 5). Due to the symptoms and the size of the diverticulum, thoracoscopic diverticulectomy was performed, with favorable outcomes.
Esophageal diverticulum are uncommon, with a reported prevalence of 0.06% to 4%. In the case of hypercontractile esophagus, a pulsion mechanism is involved, with mucosal and submucosal protrusion secondary to increased intraesophageal pressure. HRM is useful for diagnosing underlying and triggering motility disorders, as well as guiding therapeutic decisions. Management should be individualized and may range from peroral endoscopic myotomy (POEM) to laparoscopic or open surgery.

References

Figure 1. Endoscopic view of the esophageal diverticulum. A: esophageal lumen. B: diverticular lumen with food bolus inside.

Figure 2. Barium swallow study showing an epiphrenic esophageal diverticulum with a 1 cm diverticular neck.

Figure 3. Chest computed tomography showing a large esophageal diverticulum with food content and an air-fluid level. A: sagittal view. B: axial view.

Figure 4. High-resolution manometry: hypercontractile contraction pattern (Distal Contractile Integral -DCI- >8000 mmHg·s·cm). Horizontal notch in the wave contour (arrow) corresponding to the diverticular neck.

Figure 5. Image of the resected diverticulum compared with a standard surgical scissor (18 cm long).

Introduction

Advanced colorectal neoplasia (ACN) has a high potential for malignancy, and its early detection and removal can effectively reduce the incidence and mortality of colorectal cancer (CRC). A predictive model to estimate the risk of ACN could help direct patients and providers to improve screening efficiency.

Aims & Methods

We aimed to develop a comprehensive risk prediction model specifically for ACN.
A retrospective cross-sectional study was conducted on patients who underwent endoscopy at the Affiliated Wuxi People's Hospital of Nanjing Medical University from January 1, 2021, to December 31, 2023. The researchers collected clinical data, including histopathological results, demographic information, lifestyle features, and medical history. Univariate and multivariable analyses were used to derive a risk prediction model based on the training cohort of the sample, and points were assigned to each variable to create a risk score. Scores with comparable risks were grouped into different risk categories. The model and its scores were tested using the validation cohort.

Results

Among the 2054 participants in the training cohort [mean age, 60 (52, 68) years; 1022 (50.0%) female], the prevalence of ACN was 271 (13.3%). The eight-variable model (sex, age, diabetes, family history of CRC in a first-degree relative, history of colonoscopy history, smoking, gastric histopathological results, and Helicobacter pylori infection history) resulted in two risk categories, with an area under the receiver operating characteristic curve (AUC) of 0.710 (95% CI: 0.679-0.742). In the validation cohort of 495 participants with an ACN prevalence of 62 (12.5%), model performance was comparable (AUC=0.715, 95% CI: 0.649-0.781). The ACN risk was 6.9% and 23.9% in the low- and high-risk groups, respectively, and 14 and 4 participants needed to be screened in the low- and high-risk groups, respectively. Further analysis revealed that three other prediction methods, including the Asia-Pacific Colorectal Screening (APCS) score [0.622 (0.556-0.688), p=0.049], the APCS score-revised edition [0.589 (0.524-0.653), p=0.007], and the colorectal tumor prediction score [0.570 (0.504-0.636), p=0.002], displayed significantly lower AUCs than our prediction ACN model.

Conclusion

The developed and validated prediction model performed well in identifying individuals with ACN at high risk in asymptomatic Chinese populations. Colonoscopy examinations in these patients were necessary, as they not only facilitated early detection of ACN but also enabled timely intervention to prevent CRC.

Introduction

Chronic liver disease—including alcoholic liver disease (ALD), metabolic dysfunction-associated steatotic liver disease (MASLD), and liver fibrosis/cirrhosis (LFC)—has emerged as a major global health challenge, accounting for over 2 million deaths annually^1-2. Often progressing silently, chronic liver disease is frequently diagnosed at advanced stages, underscoring the urgent need for early identification of at-risk populations through reliable markers³. While recognized risk factors such as insulin resistance, alcohol overuse, and aging contribute to disease development, recent attention has focused on biological ageing acceleration (BioAgeAccel) as a comprehensive, integrative metric reflecting physiological decline, yet the utility in large populations remains underexplored^4-6. In parallel, genetic susceptibility and phenotypic data hold promise for identifying individuals predisposed to chronic liver disease⁷.

Aims & Methods

We conducted research to explore the association between BioAgeAccel, the risk of chronic liver diseases, incorporating genetic susceptibility.

This study included participants from the UK Biobank (UKB) and the All of Us (AoU) two cohort databases. BioAgeAccel was defined as the deviation between an individual’s phenotypic age (PhenoAge) or Klemera-Doubal age (KDMAge) and chronological age. Cox proportional hazards models analyzed the associations between BioAgeAccel and the risk of MASLD, ALD, and LFC, with hazard ratios (HRs) and 95% confidence intervals (CIs), and combined polygenic risk scores (PRS) to quantify genetic predisposition to chronic liver diseases.

Results

In the UKB cohort, accelerated PhenoAge was associated with significantly higher risks of ALD (HR 2.29; 95% CI 2.03-2.58), MAFLD (1.10; 1.04-1.16), and LFC (2.22; 2.01-2.46). Similarly, in the AoU cohort, accelerated PhenoAge was associated with higher risks of ALD (1.97; 1.00-3.88), MAFLD (1.35; 1.15-1.58), and LFC (2.19; 1.48-3.22). Comparable trends were observed for KDMAgeAccel in the UKB. Greater BioAgeAccel was associated with progressively higher risks of ALD and LFC, with these trends consistently. In the UKB, accelerated biological ageing was associated with chronic liver diseases independently of genetic risk and remained significant across PRS levels. Furthermore, compared to individuals with biologically younger ages and low genetic risk, participants with high genetic risk and accelerated PhenoAgeAccel exhibited the highest risk of developing chronic liver diseases, and LDSC revealed a positive genetic correlation between ageing and ALD, with SMR identifying three shared genes.

Table 1: Association between biological ageing acceleration (PhenoAgeAccel) and incident of chronic liver diseases in two datasets

Conclusion

Accelerated biological ageing was associated with increased risk of chronic liver diseases, independently of genetic risk. Identifying individuals with higher BioAgeAccel is crucial for predicting the risk of chronic liver diseases, and indicators related to the calculation of BioAgeAccel can serve as potential targets for interventions.

References

1. GBD 2019 Diseases and Injuries Collaborators. Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396(10258):1204-1222. doi:10.1016/S0140-6736(20)30925-9
2. Devarbhavi H, Asrani SK, Arab JP, Nartey YA, Pose E, Kamath PS. Global burden of liver disease: 2023 update. J Hepatol. 2023;79(2):516-537. doi:10.1016/j.jhep.2023.03.017
3. Wang Y, Huang Y, Chase RC, et al. Global Burden of Digestive Diseases: A Systematic Analysis of the Global Burden of Diseases Study, 1990 to 2019. Gastroenterology. 2023;165(3):773-783.e15. doi:10.1053/j.gastro.2023.05.050
4. Lee YB, Ha Y, Chon YE, et al. Association between hepatic steatosis and the development of hepatocellular carcinoma in patients with chronic hepatitis B. Clin Mol Hepatol. 2019;25(1):52-64. doi:10.3350/cmh.2018.0040
5. Klemera P, Doubal S. A new approach to the concept and computation of biological age. Mech Ageing Dev. 2006;127(3):240-248. doi:10.1016/j.mad.2005.10.004
6. Cohen AA, Milot E, Yong J, et al. A novel statistical approach shows evidence for multi-system physiological dysregulation during aging. Mech Ageing Dev. 2013;134(3-4):110-117. doi:10.1016/j.mad.2013.01.004
7. Martin K, Hatab A, Athwal VS, Jokl E, Piper Hanley K. Genetic Contribution to Non-alcoholic Fatty Liver Disease and Prognostic Implications. Curr Diab Rep. 2021;21(3):8. doi:10.1007/s11892-021-01377-5

Disclosure

The authors have declared no conflict of interest.

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

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

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

Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) has been performed as an alternative treatment when endoscopic retrograde cholangiopancreatography (ERCP) fails. However, EUS-HGS carries the risk of adverse events (AEs) such as peritonitis and recurrent biliary obstruction (RBO). To lower the risk of AEs, guidelines recommend the use of covered metallic stents (MS) for EUS-HGS. Several studies suggest that MS with high axial force (AF) may lead to a higher incidence of AEs such as pancreatitis and cholecystitis when MS is placed across the major duodenal papilla during ERCP. Studies comparing MS with high and low AF in EUS-HGS are scarce. MS with low AF may lower the incidence of AE in EUS-HGS. This study aimed to compare the efficacy and safety of MS with low AF (EGIS™ biliary (S&G Biotech)) and high AF (Niti-S™ biliary S-type (Taewoong Medical)).

Aims & Methods

We retrospectively reviewed consecutive patients with unresectable malignant biliary obstruction who underwent EUS-HGS with either EGIS or Niti-S across seven institutions in Japan from January 2019 to December 2022. Patients who had undergone prior biliary drainage, such as percutaneous transhepatic biliary drainage, endoscopic nasobiliary drainage, deployment of metal or plastic stents during ERCP, or EUS-HGS using a plastic stent were excluded. A matched cohort of patients was obtained using 1-to-2 propensity score matching: history of cholecystectomy, performance status, ascites, and antegrade stenting. Outcome measures included technical and clinical success, early and late AEs, time to RBO (TRBO), and overall survival (OS). Technical success, clinical success, TRBO, and OS were defined according to the Tokyo criteria 2024. AEs associated with EUS-HGS procedures were evaluated according to the adverse events in gastrointestinal endoscopy (AGREE) classification. Peritonitis was diagnosed when abdominal rebound tenderness and fluid collection on computed tomography (CT) were observed.

Results

Among 162 patients, 123 patients were eligible for the study (39 for Niti-S and 84 for EGIS). After balancing the two groups, the matched cohorts included 27 patients in the Niti-S group and 54 patients in the EGIS group. There were no significant differences in technical success rate (100% vs. 100%, p = 1.00) and clinical success rate (88.9% vs. 98.1%, p = 0.11). The RBO rates were 22.2% and 29.6% (p = 0.60). The median TRBO was 85 days for the Niti-S group and was 213 days for the EGIS group (p = 0.37), and there was no significant difference in median OS (75 vs. 112 days, p = 0.21). Early AE occurred in 10 patients (37.0%) in the Niti-S group and 8 patients (14.8%) in the EGIS group (p = 0.045). In the Niti-S group, there were 8 cases of peritonitis, 4 cases of stent migration, 2 cases of sepsis, 1 case of bleeding, and 1 case of biloma. In the EGIS group, there were 3 cases of peritonitis, 1 case of stent migration, 2 cases of cholangitis, 1 case of pancreatitis, 1 case of sepsis, and 1 case of biloma. Both groups contained cases in which multiple adverse events occurred in a single patient. Late AE were observed in 2 patients (7.4%) in the Niti-S group and 4 patients (7.4%) in the EGIS group (p = 1.00). In the Niti-S group, there were 2 cases of stent migration into the oesophagus. In the EGIS group, there was 1 case of pseudoaneurysm, 2 cases of liver abscess, and 1 case of cholecystitis.

Conclusion

The use of MS with low AF may help reduce the incidence of early AE in patients undergoing EUS-HGS.