Annals of Gastroenterology

Evaluating spleen volume in inflammatory bowel disease

2025-10-02T20:33:44+03:00

Crohn’s disease (CD) and ulcerative colitis (UC), known as inflammatory bowel disease (IBD), are characterized by immune system dysregulation. The spleen holds a primary role in systemic inflammation and immune responses. Splenic involvement or splenomegaly in IBD patients may result from secondary causes, such as portal hypertension, myeloproliferative diseases, amyloidosis, splenic abscesses or granulomas. Current research on the direct association between IBD and spleen volume (SV) has expanded significantly. In CD, SV is predominantly
increased, and is associated with worsen clinical outcomes. Successful treatment with infliximab often leads to a reduction in the elevated SV. Patients with UC often present spleens with invariant SV, or smaller spleens than those observed in CD, as UC typically affects a more limited part of the gastrointestinal tract compared to CD. However, reduction of SV in UC can also indicate relapsing pancolitis. Recent genetic data also suggest that an increased SV serves as a potential risk factor for the development of IBD, emphasizing the possible bidirectional
causal relationship between IBD and SV. Shared pathogenic pathways, including intestinal immune activation, tumor necrosis factor-α activation, bowel toxin absorption and lymphatic tissue involvement, might explain the splenic and intestinal immune dysfunction. Thus, the measurement of SV and its adjustment for body mass index or weight, factors that affect the spleen size, may serve as a potential indicator for IBD monitoring, predicting disease-related flares and complications, and evaluating the response to current biologics. Nonetheless, further insights into the underlying pathogenic pathways linking SV and IBD are considered imperative.

Keywords Spleen volume, spleen, inflammatory bowel disease, ulcerative colitis, Crohn’s disease
Ann Gastroenterol 2025; 38 (5): 465-471

Managing inflammatory bowel disease in patients receiving cancer-associated chemotherapy and beyond

2025-10-02T20:33:45+03:00

Managing patients with inflammatory bowel disease (IBD) and a current or previous history of cancer is becoming increasingly common. This scoping review aims to provide an up-to-date overview of the available literature on the management of IBD in cancer patients, including those in remission and those undergoing active cancer treatment. This scoping review was conducted, using PubMed, EMBASE and Scopus, to identify studies on IBD management in adult patients with active or prior malignancy, published between January 2019 and July 2024. Search terms included “inflammatory bowel disease” and “malignancy”. Thirty-three studies met the criteria for
inclusion; most were retrospective cohort studies. Seventeen studies analyzed incident risk of new or recurrent malignancy after starting IBD medications in patients with prior cancer. Most of these studies suggest a limited risk of cancer recurrence after restarting IBD medications. The remaining studies looked at IBD patients receiving active cancer therapy, assessing the risk of IBD relapse and/or the side effects of cancer therapy in IBD patients. Most IBD patients treated with cytotoxic chemotherapy did not experience relapse of IBD activity during therapy. However, those on either hormonal chemotherapies or immune checkpoint inhibitors were more likely to experience IBD relapse, although the data are inconsistent. This review highlights the limited cancer recurrence
risk associated with IBD therapies in cancer patients. Individualized, multidisciplinary approaches are essential for managing IBD in patients with a history of cancer. Future research should prioritize large-scale prospective studies to guide IBD and cancer management.

Keywords Inflammatory bowel disease, neoplasms, chemotherapy, biological products, scoping review

Ann Gastroenterol 2025; 38 (5): 472-487

Disparities in the burden of gastrointestinal diseases: a comprehensive analysis of data from randomized clinical trials from 2000-2023

2025-10-02T20:33:45+03:00

Background Gastrointestinal (GI) conditions, such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), metabolic dysfunction-associated steatotic liver disease (MASLD), and gastroesophageal reflux disease (GERD) are major contributors to morbidity and the healthcare burden. Randomized controlled trials (RCTs) are essential for advancing evidence-based medicine, but disparities in participant recruitment often limit the generalizability of trial findings. This study aimed to investigate demographic disparities in GI-related clinical trials, comparing trial populations to real-world data in order to identify gaps in recruitment.

Methods A cross-sectional analysis was conducted using data from United States RCTs from 2000-2023 that focused on major GI conditions: IBD, IBS, MASLD, and GERD. Demographic variables, including age, sex, gender, race and ethnicity, were collected and compared to real-world data from national health surveys. Descriptive statistics summarized the demographic distribution within the trials and highlighted disparities.

Results The analysis revealed significant disparities in recruitment across multiple GI conditions. Despite the growing burden of chronic diseases in older populations, older adults were underrepresented across trials, as a majority of participants were aged between 18 and 65 years. Sex and gender disparities were also observed, with underrepresentation of females in IBD trials and overrepresentation in IBS and MASLD trials, and no representation of gender diverse individuals. White participants were mostly overrepresented, while Black, Asian, and Hispanic individuals were underrepresented in several trials.

Conclusion This study underscores the need for more inclusive recruitment strategies in clinical trials to ensure diverse representation across age, sex, gender, and race.

Keywords Disparities, gastrointestinal, randomized controlled trial, diversity
Ann Gastroenterol 2025; 38 (5): 488-496

Device Failures and Patient-related Adverse Events Associated With Small Bowel Capsule Endoscopy: a 20-year MAUDE Database Analysis.

2025-10-02T20:33:45+03:00

Background and Aims: Small bowel capsule endoscopy (SBCE) is a critical tool in the evaluation of small bowel bleeding, detection of small bowel neoplasms and diagnosing Crohn's disease (CD). The object of this study was to examine device failures and clinical adverse events in SBCE, including those involving the patency capsule (PC) system, using user- generated reports from the U.S. Food and Drug Administration Manufacturer and User Facility Device Experience (MAUDE) database.

Methods: We analyzed post marketing surveillance data for SBCE data for the most frequently used capsule system (Pillcam®) from the MAUDE database from January 2000 until January 2024.

Results: In total, 307 medical device reports with 440 device malfunctions and 675 patient-related adverse events were identified. The most reported events were entrapment of the device (n= 236, 76.9%), failure to transmit record (n= 38, 12.4%) and failure to record (n=35, 11.4%). The most commonly reported patient-related adverse events were a foreign body retained in patient (n= 154, 50.2% ), unintentional exposure to radiation (n= 122, 39.7%), and unintended exposure to anesthesia (n= 72, 23.5%).

Conclusions: Findings from the MAUDE database regarding SBCE devices provide valuable information on device failure and patient-related adverse events. This knowledge helps operators to optimize patient selection and reduce patient risk.

Tertiary referral for double balloon enteroscopy in small bowel Crohn’s disease: a retrospective assessment of diagnostic impact

2025-10-02T20:33:46+03:00

Background Diagnosing isolated small bowel Crohn’s disease (CD) can be challenging, as symptoms, imaging, and capsule endoscopy (CE) can mimic other diseases. Double balloon enteroscopy (DBE) directly evaluates the small bowel. We describe the impact of tertiary referral for DBE in patients with known or suspected small bowel CD.

Methods We carried out a retrospective review of a single tertiary-center DBE database from February 2009 to May 2013. Patients referred for DBE for known or suspected small bowel CD, based on CE, imaging and/or symptoms were included. The primary outcome was the change in diagnosis and/or management after referral for DBE. A descriptive statistical analysis was performed.

Results A total of 108 patients were included, 10 with established CD and 98 with suspected/ruleout CD. DBE changed management in 8/10 patients with known CD. In patients with suspected CD, the diagnosis was confirmed in 39/98 (40%), and management was changed in 32 of those 39 (82%). An alternative diagnosis was made or CD was ruled out in 59/98 (60%) patients with suspected CD. Prior to DBE, starting CD therapy was recommended in 24/98 (25%) patients, but DBE confirmed CD in only 15 of those 24 (63%).

Conclusions Tertiary referral for DBE in suspected CD confined to the small bowel is valuable for investigating the findings from noninvasive testing, such as CE or imaging. DBE can guide CD management and establish accurate diagnoses. Physicians should consider DBE when the diagnosis of isolated small bowel CD is not confirmed by histology.

Keywords Crohn’s disease, diagnosis, enteritis, double balloon enteroscopy

Ann Gastroenterol 2025; 38 (5): 505-510

Effectiveness of upadacitinib in ulcerative colitis patients with prior tofacitinib exposure: a systematic review and meta-analysis

2025-10-02T20:33:46+03:00

Background Upadacitinib, a selective Janus kinase (JAK) inhibitor, is a recently approved therapy for moderate-to-severe ulcerative colitis (UC). Limited data are available on its efficacy in patients previously exposed to tofacitinib, a non-selective JAK inhibitor. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy of upadacitinib in UC patients with prior tofacitinib treatment.

Methods PubMed, Embase, Web of Science, and Cochrane Library were queried for studies evaluating the effectiveness of upadacitinib in UC patients with prior tofacitinib treatment. Primary outcomes included clinical remission, steroid-free clinical remission (SFCR), and clinical response. Secondary outcomes were the mean decrease in fecal calprotectin, and adverse events. Statistical analyses were performed using R, calculating pooled proportions with 95% confidence intervals (CI) for dichotomous outcomes and mean differences with 95%CI for continuous outcomes using a random-effects model.

Results Five studies, with 127 patients, were included in the final analysis. Upadacitinib increased pooled clinical remission rates by 57% (95%CI 0.32-0.80), SFCR rates by 52% (95%CI 0.26-0.78), and clinical response rates by 75% (95%CI 0.44-0.96). Upadacitinib reduced mean fecal calprotectin levels by 597.59% (95%CI 350.94-844.324). Adverse events, such as headache, acne vulgaris, rash, nasopharyngitis and infections, were reported in 34% of patients (95%CI 0.11-0.62).

Conclusions Our meta-analysis indicates that upadacitinib may be an effective treatment for patients with prior tofacitinib exposure, demonstrating significant clinical remission, SFCR, and clinical response. Larger clinical trials are needed to establish long-term outcomes.

Keywords Upadacitinib, tofacitinib, inflammatory bowel disease, ulcerative colitis

Ann Gastroenterol 2025; 38 (5): 511-518

Bezlotoxumab for the prevention of recurrent Clostridioides difficile infection for patients with cancer

2025-10-02T20:33:46+03:00

Background Several clinical factors increase the susceptibility of cancer patients to Clostridioides difficile infection (CDI), often resulting in lower CDI treatment response rates and higher rates of recurrent CDI (rCDI). Bezlotoxumab, a monoclonal antibody targeting and neutralizing C. difficile toxin B, demonstrates a significant reduction in rCDI rates compared to standard of care alone in the general population. However, the effectiveness of bezlotoxumab in the cancer patient population requires further investigation. We assessed the incidence of rCDI within 90 days of bezlotoxumab treatment in patients with cancer.

Methods This was a single-center retrospective cohort study conducted at a tertiary care cancer center, including patients who received bezlotoxumab with standard-of-care antibiotics for CDI or rCDI between March 2016 and January 2023. Descriptive analyses were conducted.

Results A total of 177 patients with cancer who received bezlotoxumab were included. Most (76.8%) experienced <2 CDI episodes, whereas 23.2% experienced ≥2 episodes. Bezlotoxumab was administered a median of 10 days (interquartile range [IQR] 5-12.5) after symptom onset, and fidaxomicin was the most frequently used concurrent antibiotic (41.2%). Eleven patients (6.2%) underwent fecal microbiota transplantation before or after bezlotoxumab treatment. The overall 90-day rCDI recurrence rate was 6.2% (11 patients), with a median time to recurrence of 50 days (IQR 25-58).

Conclusions Bezlotoxumab demonstrated high efficacy in reducing rCDI within a 90-day period after administration, compared to rates in the non-cancer population. The findings suggest that administration of bezlotoxumab for rCDI prevention should be considered, given the improvement in the outcome of this high-risk group.

Keywords Clostridioides difficile, recurrent, prevention, cancer, bezlotoxumab

Ann Gastroenterol 2025; 38 (5): 519-525

The therapeutic benefits of epigallocatechin gallate in rats with experimentally induced ulcerative colitis are achieved by influencing inflammation and apoptosis

2025-10-02T20:33:46+03:00

Background The potential therapeutic effects of epigallocatechin gallate (EGCG), a compound found in green tea with antioxidant and anti-inflammatory properties, on ulcerative colitis (UC) rats is a significant area of research. This study aimed to investigate the impact of EGCG on inflammation and apoptotic pathways in UC rats.

Methods The study involved inducing UC in rats by administering 2 mL of 4% acetic acid. The UC rats were then treated with 20 mg/kg of EGCG. Colon samples were collected to evaluate gene and protein expression of various factors, including nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), tumor necrosis factor alpha (TNF-α), sphingosine kinase 1 (SphK1), macrophage inflammatory protein 1-alpha (MIP-1α), B-cell lymphoma 2 (BCL2), and BCL2 associated X (BAX), as well as the activities of caspase-3/8/9. Additionally, colon sections were stained with Masson trichrome to investigate tissue fibrosis.

Results Microscopic examination of rat colonic sections stained with Masson trichrome revealed severe damage to the intestinal glands, marked by widespread hemorrhage and extensive fibrosis. Treatment with EGCG reduced the severity of the damage. Additionally, EGCG decreased the expression of several proinflammatory markers, such as NFκB and TNF-α, as well as SphK1, MIP-1α and BAX, reduced caspase-3/8/9 activity, and increased the expression of BCL2.

Conclusions The protective effects of EGCG against UC experimentally induced in rats are achieved by reducing the expression of inflammatory markers such as NFκB, TNF-α and MIP-1α, inhibiting apoptosis by decreasing the expression of BAX and caspases, and increasing the expression of BCL2.

Keywords Ulcerative colitis, rats, epigallocatechin gallate, proinflammatory markers, apoptosis

Ann Gastroenterol 2025; 38 (5): 526-536

The effects of empagliflozin on diuresis and natriuresis in patients with type 2 diabetes mellitus and liver cirrhosis

2025-10-02T20:33:46+03:00

Background We investigated the short-term diuretic and natriuretic effect of empagliflozin, a sodiumglucose linked transporter 2 inhibitor, in patients with cirrhosis and type 2 diabetes mellitus (T2DM).

Methods This was a prospective, single-arm study including 30 patients with T2DM and cirrhosis (Child-Pugh class A/B). Participants received empagliflozin 10 mg for 15 days while continuing their standard treatment. Clinical and biochemical parameters, and urinary samples, using 24-h urine collection, were recorded before and after treatment. Twenty-seven patients continued empagliflozin for 6 months and were assessed for glycemic control and renal function.

Results Empagliflozin increased median daily urine volume by 475 mL (P=0.010) and fractional sodium excretion (FENa) by 16% at day 15 (P=0.030), but the 8 mmol/L increase in 24-h sodium excretion was not significant. Empagliflozin also reduced body weight (-0.8 kg, P<0.001) and systolic blood pressure (-4 mmHg, P=0.029). Glycemic control remained unremarkable at day 15, but improved at 6 months (baseline vs. 6 months: fasting glucose 146 vs. 116 mg/dL, P=0.016; glycosylated hemoglobin 6.2% vs. 6%, P=0.011). Compared to baseline (89.1±20.6 mL/min/1.73m2, estimated glomerular filtration rate declined numerically but not statistically significantly at day 15 (85.2±21.8, P=0.056 and at 6 months (82.8±23.7, P=0.035. No serious adverse events were noticed.

Conclusions Up to 6 months’ empagliflozin administration in patients with cirrhosis and T2DM seems safe and increases urine output and FENa, but its impact on renal function requires further investigation. Larger randomized controlled trials are needed to confirm its long-term efficacy and safety in this setting.

Keywords Cirrhosis, diabetes, empagliflozin, diuresis, natriuresis

Ann Gastroenterol 2025; 38 (5): 537-544

Impact of overt and subclinical hepatogenous diabetes and metformin treatment on circulatory function, renal function and hemodynamics, inflammatory activity, and prognosis in patients with cirrhosis and ascites

2025-10-02T20:33:47+03:00

Background Hepatogenous diabetes (HD) is common in advanced cirrhosis. The oral glucose tolerant test (OGTT) is frequently diagnostic, as fasting blood glucose (FBG) may be normal. We investigated the impact of FBG- and OGTT-diagnosed HD, and metformin treatment, on circulatory function, renal function and perfusion, and inflammatory activity in patients with cirrhosis and ascites. Also, long-term prognosis of HD under metformin/metformin-based treatment was assessed.

Methods Mean arterial pressure (MAP), cardiac output (CO), systemic vascular resistance (SVR) as MAP/CO ratio, plasma renin activity (PRA), plasma aldosterone, glomerular filtration rate (GFR), renal blood flow (RBF), and plasma levels of lipopolysaccharide-binding protein (LBP), tumor-necrosis factor-α (TNF-α) and interleukin-6 were evaluated at baseline in patients with and without HD, and after 6 months of metformin treatment for newly diagnosed HD.

Results Compared to OGTT-HD (n=34) and no-HD (n=37), FBG-HD patients (n=35; newlydiagnosed, n=13) had significantly lower SVR (P=0.02/P=0.01), GFR (P=0.01/P=0.008) and RBF (P=0.02/P=0.01), and significantly higher CO (P=0.04/P=0.03), PRA (P=0.009/P=0.006), and levels of LBP (P=0.01/P=0.008) and TNF-α (P=0.03/P=0.02). Initiation of metformin in OGTTHD and FBG-HD patients induced significant increases in SVR (P=0.02/P=0.04), GFR (P=0.02/
P=0.04) and RBF (P=0.04/P=0.05), and significant decreases in PRA (P=0.02/P=0.03) and LBP (P=0.02/P=0.04). Three-year survival in OGTT-HD was significantly higher than in FBG-HD (75.3% vs. 55.3%; P=0.03) and similar to no-HD (81.7%).

Conclusions Circulatory function and renal function and perfusion are aggravated by FBG-HD compared to OGTT-HD or no-HD, possibly because of greater inflammatory activity, while they improve significantly after metformin treatment. Early treatment of HD with metformin may improve prognosis.

Keywords Hepatogenous diabetes, oral glucose tolerant test, metformin, systemic inflammation, circulatory function

Ann Gastroenterol 2025; 38 (5): 545-553

Endoscopic ultrasonography-guided gastroenterostomy for malignant and benign gastric outlet obstruction: a systematic review and meta-analysis

2025-10-02T20:33:47+03:00

Background Endoscopic ultrasonography-guided gastroenterostomy (EUS-GE) with a lumenapposing metal stent has been proposed as a treatment for patients with gastric outlet obstruction (GOO). We performed a systematic review and meta-analysis to compute the technical success, clinical success and complication rates of EUS-GE in treating GOO due to either neoplastic or benign diseases.

Methods The literature search was conducted in PubMed, EMBASE and the Cochrane Central Register of Controlled Trials, from inception until January 23, 2025, according to the PRISMA and MOOSE statement guidelines. The primary objective was to assess both technical and clinical success. A secondary outcome was to rate the adverse events.

Results Data from 39 studies involving 2845 patients were analyzed. The pooled technical success rate was 95.1%, and the procedure was successful in 95.3% and 95.1% of patients with malignant or benign diseases, respectively. Clinical success was achieved in 93.5% of all patients where the procedure had technical success, and in 93.1% and 94.4% of those treated for malignant and benign conditions, respectively. The overall rate of adverse events was 18.5%, including perforation (4.4%), bleeding (2.7%), stent migration (1.4%), stent closure (3.3%), infection (4.4%), and fistula (2.3%). The procedure-related mortality was 1.4%.

Conclusion EUS-GE appears to be a viable approach for the treatment of GOO patients, for both malignant and benign diseases, with favorable outcomes and an acceptable safety profile.

Keywords Endoscopic ultrasonography, gastroenterostomy, gastric outlet obstruction, lumenapposing metal stent

Ann Gastroenterol 2025; 38 (5): 554-563

Trends and outcomes of endoscopic ultrasound-guided drainage and pancreatic necrosectomy for acute necrotizing pancreatitis

2025-10-02T20:33:47+03:00

Background Use of endoscopic ultrasound (EUS)-guided interventions has resulted in an expanding domain of non-surgical endoscopic methods for treating acute necrotizing pancreatitis (ANP). We examined the current trends and outcomes of EUS-guided drainage and endoscopic necrosectomy in the United States.

Methods This observational retrospective study used the Nationwide Inpatient Sample database (2016-2020) to identify adult patients with ANP who underwent endoscopic necrosectomy, based on ICD-10-CM codes. Univariate and multivariate logistic regression, and linear models were used to examine the outcomes of ANP in patients who underwent endoscopic necrosectomy in comparison to patients who had no such interventions.

Results Among 11,212 ANP cases identified, 493 (4.4%) underwent endoscopic necrosectomy. The patients’ mean age was 49.6 years and they were predominantly male (66.8%). There was a steady increase in ANP admissions (542 to 3180) and endoscopic necrosectomy (0% to 5.8%) from 2016-2020. Endoscopic intervention had lower odds for systemic inflammatory response syndrome (P=0.038), but higher odds for venous thromboembolism (P=0.006). Hospital costs (P<0.001), charges (P<0.001), and length of hospital stay (LOS) (P<0.001) were greater for patients with endoscopic intervention. Procedural adverse events were rare (5.9%), and were associated with significantly greater LOS (P=0.004), higher hospital costs (P=0.018) and charges (P=0.004), but no difference in mortality (P=0.899).

Conclusions Endoscopic necrosectomy for ANP increased from 2016-2020 and was associated with low risk for adverse events or mortality, but greater LOS and costs compared to conservative non-interventional management. Further research is required to optimize patient selection and address the economic implications.

Keywords Acute pancreatitis, necrotizing pancreatitis, pancreatic necrosis, endoscopic necrosectomy, endoscopic ultrasound-guided drainage

Ann Gastroenterol 2025; 38 (5): 564-569

Effectiveness of prophylactic pancreatic stents in preventing post-endoscopic retrograde cholangiopancreatography pancreatitis in high-risk patients: a 16-year comprehensive study

2025-10-02T20:33:47+03:00

Background Cannulation of the common bile duct (CBD) during endoscopic retrograde cholangiopancreatography (ERCP) can be technically challenging, especially when repeated unintended pancreatic duct cannulation occurs. We evaluated the effectiveness of prophylactic pancreatic stent (PS) placement in preventing post-ERCP pancreatitis (PEP) under such conditions. This is the first comprehensive study of its kind conducted in Greece, and one of the few in Europe.

Methods This retrospective study included patients who underwent their first ERCP between January 1, 2008, and March 1, 2024, and received a PS after inadvertent pancreatic duct cannulation on 3 or more attempts. From 2015 onward, rectal diclofenac was administered to all patients as a preventive measure for PEP.

Results In a total of 6080 ERCP procedures, 421 patients met the inclusion criteria (46.1% male; mean age 67.8±15.8 years). The most common indications were choledocholithiasis (57.7%), malignant obstruction (26.6%), and benign CBD strictures (5.7%). Successful CBD cannulation during the initial session was achieved in 86.4% of cases. Additional techniques included transpancreatic sphincterotomy (2.6%) and needle-knife precut (1.4%). A second ERCP was performed in 7.8% of cases, achieving successful CBD cannulation in all. PEP occurred in 4.9% of patients, with severe cases accounting for only 0.7%. PEP was significantly more frequent in women (P=0.001), while diclofenac did not significantly reduce its incidence (P=0.4). There were 3 deaths, 1 related to PEP (0.2%).

Conclusion PS placement effectively reduces severe PEP risk following difficult CBD cannulation and supports high success rates in repeat ERCP, while diclofenac showed no significant additional benefit.

Keywords Endoscopic retrograde cholangiopancreatography, pancreatitis, pancreatic stents, prevention

Ann Gastroenterol 2025; 38 (5): 570-576

Reassessing Clostridioides difficile trends and racial disparities

2025-10-02T20:33:47+03:00

Authors’ reply

2025-10-02T20:33:48+03:00