Annals of Gastroenterology

Landscape of B lymphocytes and plasma cells in digestive tract carcinomas

Konstantina Dimopoulou — 2025-01-14

Digestive tract carcinomas are the most commonly occurring cancers worldwide, but their prognosis with traditional treatments remains poor. T lymphocytes are well-recognized as crucial components of effective anti-tumor immunity, and current immunotherapeutic strategies concentrate mainly on T-cell-mediated immunity reinforcement, whereas the role of B lymphocytes and plasma cells (PCs) has been neglected in the past, and it is only recently that these cells have been considered as key players in the tumor microenvironment (TME). In this review, we describe the complex dual role of B lymphocytes and PCs in promoting and inhibiting tumor progression in the TME of digestive tract carcinomas, and we demonstrate their prognostic value. Furthermore, we highlight their controversial function in cancer and nominate them as additional therapeutic targets for the development of new treatment interventions that might alter the dismal prognosis of digestive tract tumors.

Keywords B lymphocytes, plasma cells, digestive tract carcinomas

Ann Gastroenterol 2025; 38 (1): 1-11

Diagnostic approach to patients with suspected motility disorders: one size does not fit all

Theodoros Voulgaris — 2025-01-14

Background Dysphagia and retrosternal chest pain are considered typical manifestations of major esophageal motility disorders (mEMD). High-resolution manometry (HRM) is the gold standard for mEMD diagnosis, while endoscopy and barium swallow are ancillary tools. We aimed to investigate the frequency of mEMD among patients referred for HRM with typical compared to non-typical symptoms. We also evaluated endoscopic and barium swallow data from patients with mEMD who underwent HRM.

Methods We retrospectively collected epidemiological, endoscopic, barium swallow, and HRM data from 302 patients. Atypical symptoms were considered to be heartburn, regurgitation, globus, oropharyngeal dysphagia, and epigastric pain.

Results The main referral symptoms were: esophageal dysphagia, 58.3%; chest pain, 13.7%; heartburn, 8.9%; regurgitation, 8.3%; and globus/oropharyngeal dysphagia/epigastric pain, 10.8%. A diagnosis of mEMD was more common when typical symptoms existed (69.9% vs. 15.4%, P<0.001). The majority of patients with mEMD in HRM, independently of their symptoms, had an abnormal barium study (typical: 94.8% vs. non-typical: 100%, P=0.633), while compatible endoscopic data tended to be observed more frequently among patients with typical symptoms (69.1% vs. 40%, P=0.057). An HRM diagnosis of mEMD among patients with compatible findings from either barium swallow or endoscopic examination was statistically more frequent among patients with typical symptoms (92.4% vs. 52.6%, P<0.001).

Conclusions More than half of patients referred for HRM will be diagnosed with mEMD, at a higher rate when typical symptoms are reported. A lack of compatible endoscopic and barium swallow findings, in the absence of typical symptoms, makes the diagnosis of mEMD almost impossible.

Keywords Major esophageal motility disorders, typical symptoms, high-resolution manometry, upper gastrointestinal endoscopy, time-barium esophagogram

Ann Gastroenterol 2025; 38 (1): 12-19

Peroral endoscopic myotomy (Z-POEM) versus flexible endoscopic septotomy (FES) for treatment of Zenker’s diverticulum: does either make the cut? A systematic review and meta-analysis of outcomes

Sahib Singh — 2025-01-14

Background Endoscopic treatments of symptomatic Zenker’s diverticulum (ZD) include flexible endoscopic septotomy (FES) and, more recently, peroral endoscopic myotomy (Z-POEM). Data comparing these techniques are limited. We conducted a meta-analysis evaluating FES vs. Z-POEM for symptomatic ZD.

Methods Multiple databases were searched from inception to September 2024. Our primary outcomes were clinical and technical success. Secondary outcomes included adverse events, length of hospital stay (LOS), procedure time, and recurrence. A random-effects model was used, and outcomes were represented as pooled rates, relative risk (RR) and standardized mean difference (SMD), along with 95% confidence intervals (CI).

Results Seven studies with 580 patients (Z-POEM=274, FES=306) were included. Mean age ranged from 68.9-74.9 years. The diverticulum size was not statistically different between the 2 groups: SMD -3.78 (-11.68 to 4.12), P=0.35. The pooled technical success was similar for Z-POEM and FES: RR 0.99 (95%CI 0.96-1.02; I2=0%); P=0.4. Clinical success rate was significantly higher for Z-POEM compared to FES: RR 1.11 (95%CI 1.04-1.18; I2=16%); P=0.001. There were no statistically significant differences between the 2 treatment modalities in pooled rate of recurrence, adverse events, LOS or procedural time.

Conclusions Our analysis shows that Z-POEM and FES in the treatment of symptomatic ZD are both associated with high technical success and a good safety profile, and have comparable procedural times and rates of recurrence. Z-POEM may offer higher rates of clinical success at follow up.

Keywords Zenker’s diverticulum, Z-POEM, septotomy

Ann Gastroenterol 2025; 38 (1): 20-27

Simethicone with or without N-acetylcysteine as premedication in esophagogastroduodenoscopy: a systematic review and meta-analysis

Caroline Tanadi — 2025-01-14

Background The impairment of gastrointestinal mucosa visibility during esophagogastroduodenoscopy (EGD), due to the presence of foam and bubbles, may lead to reduced quality in the EGD results. The combination of simethicone, a defoaming agent, along with N-acetylcysteine (NAC), which has mucolytic properties, has been proposed to improve the visibility of the mucosa. This study aimed to evaluate the effectiveness of pre-procedural
administration of simethicone and N-acetylcysteine in improving mucosal visibility, procedure time and mucosal cleansing volume needed during EGD.

Methods We conducted a comprehensive literature search from inception to November 23, 2023, in PubMed, CENTRAL, ProQuest, SAGE, and JSTOR. We included randomized clinical trials that investigated the effects of simethicone with or without NAC as premedication in EGD. For the quantitative analysis, standardized mean difference (SMD) was used to assess continuous outcomes and risk ratio for dichotomous outcomes. The Cochrane risk of bias 2 tool was used to evaluate the risk of bias.

Results This meta-analysis comprised a total of 20 studies and found that simethicone with or without NAC improved mucosal visibility compared with control (SMD -1.27, 95% confidence interval [CI] -1.74 to -0.81, P<0.001). The combination of simethicone and NAC was significantly better than simethicone alone (SMD -0.68, 95%CI -1.08 to -0.28, P=0.001). Simethicone with or without NAC also shortened the procedure time compared to control
(MD -1.40, 95%CI -2.67 to -0.12, P=0.03). The risk of bias was low with a moderate grade of certainty.

Conclusion The administration of simethicone with or without NAC may improve EGD quality.

Keywords Simethicone, N-acetylcysteine, premedication, esophagogastroduodenoscopy, metaanalysis

Ann Gastroenterol 2025; 38 (1): 28-40

Early rebleeding rate following endoscopic treatment of colonic diverticular bleeding: a systematic review and meta-analysis

Isha Delaleeuwe — 2025-01-14

Background Various endoscopic treatment options are available for managing colonic diverticular bleeding (CDB). We conducted a systematic review and meta-analysis to assess the effectiveness of these endoscopic interventions in achieving hemostasis in patients with CDB, focusing on early rebleeding rate (ERR) within 30 days.

Methods A systematic literature search of the PubMed and Cochrane Library databases was performed for articles published between January 2008 and December 2023. Studies evaluating endoscopic clipping, with or without epinephrine injection, endoscopic band ligation (EBL) and endoscopic snare ligation (EDSL) in the treatment of CDB were included. The primary outcome was the overall pooled ERR following successful hemostasis. Secondary outcomes addressed ERRs associated with various hemostatic endoscopic techniques, and pooled ERRs for both direct and indirect clipping methods. Results are presented as pooled rates and odds ratio (OR) with 95% confidence intervals (CI).

Results Sixteen studies were included, comprising 1435 patients with definite CDB of whom 1273 received endoscopic hemostatic treatment. Overall pooled ERR was 14.73% (95%CI 9.33-20.14%). Pooled ERRs were 9.83% (95%CI 7.41-12.26%) in the EBL/EDSL group and 22.32% (95%CI 12.48-32.16%) in the endoscopic clipping group (P=0.02). A subgroup analysis of the clipping group showed a significant difference between the pooled ERRs favoring direct clipping: 12.04% (95%CI 3.06-21.02%) vs. 27.74% (95%CI 18.34-37.14%), P=0.02. The measured effect favors direct over indirect clipping in reducing early rebleeding episodes: OR 0.45, 95%CI 0.24-0.85; P=0.01.

Conclusion In the management of patients presenting with CDB, EBL/EDSL and direct clipping showed significantly lower ERRs compared to indirect clipping.

Keywords Colonic diverticular bleeding, endoscopy, hemostasis, treatment

Ann Gastroenterol 2025; 38 (1): 41-50

Impact of pericarditis on cardiovascular complications and healthcare utilization in patients with inflammatory bowel disease: a National Inpatient Sample study

Ayushi Garg — 2025-01-14

Background Inflammatory bowel disease (IBD), which affects over 2.3 million people in the USA, involves chronic gut inflammation and can lead to cardiovascular complications, including pericarditis. Whether pericarditis in IBD patients is caused by medication, or by the disease itself, remains unclear. Our study aimed to determine the prevalence of pericarditis in IBD and its impact on cardiac complications, outcomes and resource utilization.

Methods NIS data were obtained for IBD patients from 2016-2020. Outcomes were assessed using multivariate logistic regression, adjusting for demographics, hospital characteristics, comorbidities, and IBD etiology.

Results In our study of 1.52 million IBD patients, 0.6% had pericarditis, of whom a majority were women (54.1%) and white (76.3%), over 65 years old (43.1%), enrolled in Medicare (51.7%), and living in urban areas (96.3%). Adjusting for confounding factors, IBD patients with pericarditis had higher odds of cardiac arrest (adjusted odds ratio [aOR] 2.73, 95% confidence interval [CI] 1.90-3.91), cardiogenic shock (aOR 6.42, 95%CI 4.77-8.64), and ventricular arrhythmia (aOR 2.13, 95%CI 1.63-2.78 (P<0.001 for all).

Conclusions Our study found that pericarditis, though rare at 0.6%, significantly impacts cardiovascular health and healthcare utilization in IBD patients, with higher prevalence of pericarditis in older individuals, females, and those with comorbidities such as diabetes, hypertension or chronic kidney disease highlighting the need for further research to enhance therapeutic approaches and patient care.

Keywords Inflammatory bowel disease, pericarditis, cardiovascular complications, cardiac arrest, cardiogenic shock

Ann Gastroenterol 2025; 38 (1): 51-59

Endoscopic management of ileal pouch–anal anastomosis strictures: meta-analysis and systematic literature review

Parth Patel — 2025-01-14

Background Restorative proctocolectomy with ileal pouch–anal anastomosis (IPAA) is a common surgical procedure for ulcerative colitis and familial adenomatous polyposis. IPAA strictures are a known complication, often requiring surgical intervention. Endoscopic interventions offer a less invasive alternative, but their safety and efficacy remain uncertain.

Methods A comprehensive literature search was performed to identify pertinent studies. Outcomes assessed were technical success, clinical success (immediate and end of follow up), pouch failure rate and adverse events. Pooled estimates were calculated using random effects models with a 95% confidence interval.

Results A total of 607 patients from 9 studies were included. Technical success, defined as the ability to pass the endoscope through the stricture, was achieved in 97.4% of patients. Immediate clinical success, defined as symptom improvement post-intervention, was seen in 44.5% of patients. Clinical success at the end of follow up was observed in 81.7% of patients. However, 6.8% of patients experienced pouch failure and ultimately 14.5% required surgical intervention for refractory strictures or complications. Endoscopic intervention-related serious adverse events occurred in 3.9% of patients, including perforation and major post-procedural bleeding.

Conclusions Endoscopic interventions for IPAA strictures demonstrate high technical success rates, providing a less invasive option for managing this complication. While clinical success rates immediately post-procedure and at end of follow up are promising, a significant proportion of patients ultimately require surgical intervention for pouch failure or refractory strictures.

Keywords Ileal pouch–anal anastomosis, endoscopic balloon dilation, stricturotomy

Ann Gastroenterol 2025; 38 (1): 60-67

Diverticulosis and neoplastic lesions in screening colonoscopy: a large, multicenter study

Paolo Fedeli — 2025-01-14

Background Data on the potential association between diverticulosis and colonic neoplastic lesions are still controversial. We investigated this issue in subjects who underwent screening colonoscopy.

Methods We reviewed the data of subjects with a positive fecal immunological test who underwent a first colonoscopy in the national colorectal screening program. Endoscopic and histological reports were evaluated, using both univariate and multivariate analyses to search for an association between diverticulosis and colonic neoplastic lesions.

Results Data from 5050 subjects (males: 52.2%; mean age: 61.7±6.5 years) observed in the 7 participating centers were considered. Diverticula were found in 2176 (43.1%) cases; at least 1 adenoma was detected in 2277 (45.1%) patients, at least 1 advanced adenoma in 842 (16.7%); and cancer was diagnosed in 159 (3.1%) cases. By univariate analysis, the prevalence of adenomas in patients with diverticula (46.7%, 95% confidence interval [CI] 44.6-48.8%) was significantly higher than in controls (43.8%, 95%CI 42.1-45.7%; P=0.041), while prevalences of both advanced adenomas (13.8%, 95%CI 16.3-19.5%) and cancers (2.4%, 95%CI 1.7-3.1% vs. 3.7%, 95%CI 3.1-4.4%) were lower. By multivariate analysis, only male sex (odds ratio [OR] range: 1.54-2.05) and age (OR range: 1.03-1.05) were found to
be independent variables associated with different neoplastic lesions in the colon, whilst diverticulosis was not.

Conclusion This large, multicenter study found no significant association between diverticulosis and neoplastic lesions in subjects who underwent screening colonoscopy.

Keywords Diverticulosis, adenoma, cancer, screening, colonoscopy

Ann Gastroenterol 2025; 38 (1): 68-71

Immune checkpoint inhibitor-associated gastrointestinal adverse events in patients with colorectal cancer

Antonio Pizuorno Machado — 2025-01-14

Background Immune checkpoint inhibitors (ICI) target microsatellite instability-high (MSI-H) tumors with success. The incidence and characteristics of ICI-related colitis (IMC) in patients with MSI-H colorectal cancers (CRC) are unclear.

Methods We performed a retrospective analysis of adult patients with CRC who received ICI between June 1, 2014, and December 31, 2022, including data on IMC observed up to 3 months after the last dose of ICI. Patients’ demographics, oncologic profile, endoscopic features, treatment and clinical outcomes were evaluated.

Results Of 474 patients with CRC receiving ICI during our study period, 18 developed IMC (3.8%). The majority were Caucasian (88.8%), male (61.1%), and their median age was 69.5 years. Of these patients, 50% received combination therapy with anti-PD-1/L1 and CTLA-4; 66.6% had MSI-H colorectal cancer, 11.1% had a second cancer-melanoma, while 61.2% and 66.7% had grade 1-2 colitis and diarrhea respectively. Endoscopic evaluation was used in 5 patients, of whom 2 had ulcerative inflammation necessitating selective immunosuppressive therapy with biologics. Therapy was withheld in 61.1% because of toxicity; 41.4% and 5.8% were noted to have median Common Terminology Criteria for Adverse Events grade 2 liver and pancreas toxicity respectively. The majority of our cohort received steroid therapy.

Conclusions The lower severity of IMC, compared to toxicity in other ICI-treated cancers, may be influenced by the tumor microenvironment in MSI-H colorectal cancer after ICI exposure. Larger prospective studies are necessary to determine the role of tumor biology and the gut microbiome in the disease profile and severity of IMC.

Keywords Immune checkpoint inhibitors, colorectal cancer, immune-related adverse event, colitis

Ann Gastroenterol 2025; 38 (1): 72-79

Gastrointestinal cancer incidence after lung transplantation in sarcoidosis patients

Graham Saeed — 2025-01-14

Background The risk of gastrointestinal (GI) cancer after lung transplantation (LTx) in sarcoidosis patients is not well defined. Given the cancer risks linked to sarcoidosis and organ transplantation, this study investigated the incidence of GI de novo malignancies (DNM), comparing LTx recipients with sarcoidosis or idiopathic pulmonary fibrosis (IPF).

Methods We analyzed data from the United Network for Organ Sharing registry, including adults with sarcoidosis or IPF who underwent LTx between May 2005 and December 2018. The primary outcome was the incidence of GI DNM by March 2023.

Results Of 7996 lung transplant recipients, 108 (1.35%) developed GI malignancies posttransplantation. Among these, 662 patients (9%) had sarcoidosis and 7334 (91%) had IPF. Sarcoidosis patients showed a non-significant trend toward a higher risk of GI malignancies compared to those with IPF (subhazard ratio 1.72, 95% confidence interval 0.90-3.29; P=0.099), with no observed difference in the risk of non-GI cancers.

Conclusions The overall incidence of GI DNM following LTx is low, and sarcoidosis does not appear to increase the risk of GI cancers compared to IPF. This finding suggests that enhanced GI cancer screening beyond standard guidelines may not be warranted in this population, allowing for targeted surveillance of more prevalent malignancies in sarcoidosis patients post-LTx.

Keywords Gastrointestinal cancer, de novo malignancy, idiopathic pulmonary fibrosis, immunosuppression, lung transplantation

Ann Gastroenterol 2025; 38 (1): 80-84

The treatment interventions and targets of cancer cachexia research during the past decade: a systematic review of the literature

Panagiotis Filis — 2025-01-14

Background Cachexia is a detrimental multifactorial syndrome that has been strongly associated with cancer. A growing body of data concerning its management is being generated from the ongoing advances of experimental cancer cachexia research. This study aimed to delineate the broad landscape of cancer cachexia research, by comprehensively presenting the treatment interventions and targets of cancer cachexia during the past decade.

Methods A systematic literature search was performed in Medline and Scopus databases from January to April 2023. Articles were considered eligible if they described any type of intervention in tumor-bearing rodents to study the effect on prevention or treatment of cancer cachexia. The corresponding signaling and metabolic pathways that were targeted by these interventions were documented.

Results A total of 271 articles were considered eligible for our study. Of these, 176 studies pertained to pharmaceutical interventions with 100 corresponding targets, 58 studies pertained to nutritional interventions with 60 corresponding targets, and 37 studies pertained to exercise interventions with 60 corresponding targets.

Conclusions The continuous evolution of cancer cachexia research has provided a plethora of disease targets and corresponding treatment interventions. Moving forward, the available management strategies should be refined and clinical research should efficiently capitalize on the robust experimental evidence.

Keywords Cancer, cachexia, treatment, mechanism, pathway

Ann Gastroenterol 2025; 38 (1): 85-92

Validation of gender-equity model for liver allocation (GEMA) and its sodium variant (GEMA-Na) in candidates for liver transplantation

Magdalini Adamantou — 2025-01-14

Background The current allocation system for liver transplantation (LT) is based on the sickestfirst policy, using objective variables to ensure equal priority. However, under-prioritization of female patients for LT, compared to males, is well demonstrated and new scores have been proposed to overcome this systematic bias. This study evaluated the ability of these new scores to predict the long-term outcomes of patients with cirrhosis.

Methods The clinical and laboratory characteristics of 694 consecutive candidates for liver transplantation from 2 liver transplant centers were recorded. The model for end-stage liver disease (MELD)-based scores (MELD, MELD-Sodium and MELD 3.0), as well as the Gender-Equity Model for liver Allocation (GEMA) and GEMA-Sodium, were used to assess the severity of liver disease. Patients were followed-up prospectively and their outcomes assessed.

Results During a follow-up period of median length 12 months (range: 4-52), 28.5% of patients died, 21% of patients underwent LT, while 50.5% remained alive. Female patients had significantly lower MELD and MELD-Sodium scores compared to males, attributable to their significantly lower creatinine, while MELD 3.0, GEMA and GEMA-Sodium did not differ between the 2 sexes. In multivariate Cox regression analysis, GEMA-Sodium was the only factor independently associated with death/LT, and showed very good discriminative ability (hazard ratio 1.10, 95% confidence interval 1.073-1.128; P<0.001). These findings were confirmed in several subgroup analyses.

Conclusions Our findings show for the first time the predictive ability of GEMA-Sodium for the long-term outcomes of LT candidates. However, further studies are needed to confirm these findings.

Keywords GEMA, GEMA-Na, MELD, liver transplantation, prognosis

Ann Gastroenterol 2025; 38 (1): 93-99

Clinical features and outcomes of total pancreatic lipomatosis with chronic pancreatitis: a case series

Surinder S. Rana — 2025-01-14

Background Fatty changes in the pancreas are common, whereas total pancreatic lipomatosis (PL) is rare. Commonly associated with various components of metabolic syndrome and metabolicassociated steatotic liver disease, total PL can have various etiologies and can manifest with severe pancreatic exocrine insufficiency.

Method We retrospectively analysed the clinical profile and management outcomes of 8 patients (mean age: 37.1 years; 5 male) with total PL seen at a tertiary care center over the last 15 years.

Results All patients presented with abdominal pain and had coexistent chronic pancreatitis, while 5/8 (62%) patients had metabolic syndrome. None of the patients had a history of acute pancreatitis or congenital syndromes, nor developed pancreatic carcinoma in the follow up. Seven (87%) patients had pancreatic ductal dilatation and calcification. All patients had pancreatic exocrine insufficiency, while 5/8 (52%) patients had endocrine insufficiency. Six (75%) patients were successfully managed with pancreatic endotherapy.

Conclusions Pancreatic endotherapy is safe and effective in the treatment of abdominal pain in patients who have chronic pancreatitis with total PL. These patients have a high frequency of pancreatic exocrine as well as endocrine insufficiency.

Keywords Chronic pancreatitis, fatty pancreas, endosonography, diabetes

Ann Gastroenterol 2025; 38 (1): 100-104

Impact of aspirin on pancreatic cancer

Christos Zavos — 2025-01-14

Authors’ reply

Thanathip Suenghataiphorn — 2025-01-14