Journal of Gastroenterology最新文献

Background: The prognosis and recurrence patterns of early-diagnosed pancreatic ductal adenocarcinoma (PDAC), particularly following surgical resection, remain unclear.

Methods: This multicenter retrospective study analyzed patients who underwent surgical resection for PDAC between 2005 and 2023. Patients were categorized according to pathological stages 0, I, and II. Recurrence patterns and survival outcomes were compared among the three groups. Multivariate analysis was performed to identify independent risk factors for remnant pancreatic recurrence, including early-stage disease, postoperative follow-up of more than 5 years, and receipt of adjuvant chemotherapy.

Results: A total of 349 patients were included: 51 with stage 0, 77 with stage I, and 221 with stage II PDAC. The 5-year overall survival rates were 87%, 71%, and 49% for patients with stage 0, I, and II PDAC, respectively. Remnant pancreatic recurrence was observed in 10% of patients with stage 0 PDAC and 18% of patients with stage I PDAC, compared with 5% of those with stage II PDAC. Recurrence was significantly more frequent in stage I (P < 0.001) and tended to be higher in stage 0 (P = 0.062) than in stage II. Multivariate analysis identified pathological stage 0-I and postoperative follow-up of > 5 years as independent risk factors for remnant pancreatic recurrence.

Conclusions: Patients with early-stage PDAC exhibit a higher risk of remnant pancreatic recurrence than those with stage II disease. These findings underscore the importance of long-term pancreas-focused surveillance in early-stage PDAC to enable timely detection of late recurrence and potentially improve patients outcomes.

Background: Very-early-onset inflammatory bowel disease (VEO-IBD), representing cases diagnosed before age 6 years, is increasing in prevalence. Although VEO-IBD often presents as severe, treatment-resistant disease requiring biologic agents, studies showing the effectiveness of biologics, such as ustekinumab (UST) and vedolizumab (VDZ), remain limited.

Methods: We retrospectively analyzed patients with VEO-IBD treated for at least a year from 13 institutions in Japan, evaluating clinical course including effectiveness of biologics, such as infliximab (IFX), adalimumab (ADL), UST, and VDZ. Patients with monogenic IBD were excluded. Steroid-free clinical remission (SFCR) and treatment persistence were assessed separately for first-line and for second-line or subsequent biologic therapies.

Results: We studied 101 VEO-IBD patients (56% male; median age, 3.6 years), including 40 with Crohn's disease, 52 with ulcerative colitis, and 9 with unclassified IBD. Biologics were used in 67 patients, most commonly infliximab (IFX; n = 52), followed by UST (n = 38), adalimumab (ADL; n = 23), and VDZ (n = 21). As first-line therapy, IFX and ADL achieved 1-year SFCR rates of 19% and 46%, with persistence rates of 36% and 48%. Despite being used mainly as second-line or subsequent therapies, UST and VDZ showed 1-year SFCR rates of about 45% and 36%, and maintained persistence of 79% and 46%, respectively, with UST demonstrating higher persistence than TNF-α inhibitors (P < 0.01). No discontinuations due to infusion reactions or other adverse events occurred with UST or VDZ.

Conclusion: UST and VDZ were effective and well tolerated even when used as second-line or subsequent therapies for VEO-IBD.

Background: Lenvatinib is widely used in hepatocellular carcinoma (HCC), but its efficacy following atezolizumab plus bevacizumab remains unclear. This study compared the therapeutic impact of lenvatinib administered after immunotherapy, following its use as a first-line systemic therapy.

Methods: This retrospective study analyzed patients with unresectable HCC who received lenvatinib either after atezolizumab plus bevacizumab as second-line therapy or as first-line therapy. Propensity score matching (PSM) was applied to balance baseline characteristics. Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were compared.

Results: Following PSM, 63 matched pairs were analyzed. The "After Atezo + Beva" group had larger and more advanced intrahepatic tumors, but PSM balanced the groups' baseline characteristics. Based on mRECIST, the objective response rate and disease control rate were 41.1% and 80.4% in the "After Atezo + Beva" group, and 49.2% and 76.3% in the first-line group. Based on RECIST version 1.1, these were 25.0% and 80.4% vs. 28.8% and 76.3%, respectively. Median PFS was 4.5 vs. 5.2 months (p = 0.233) and median OS was 14.3 vs. 16.0 months (p = 0.769). Grades ≥ 3 AEs occurred more frequently in the "After Atezo + Beva" group (74.9% vs. 50.8%, p = 0.006), with grades ≥ 3 proteinuria in 31.7% vs. 14.3% (p = 0.020) and grades ≥ 3 fatigue in 12.7% vs. 1.6% (p = 0.033).

Conclusions: Lenvatinib demonstrated comparable efficacy whether used following atezolizumab plus bevacizumab or as first-line therapy in unresectable HCC. These findings support its clinical utility in the post-immune checkpoint inhibitor setting, with attention to AE management.

Background: Pancreatic cancer (PC) has a poor prognosis. To overcome this poor prognosis, early detection is mandatory and the development of highly sensitive biomarkers is required. This study aimed to explore a novel and valuable biomarker based on serum peptidomic analysis for screening patients with PC, especially in the early stages.

Methods: Serum samples were collected from 106 patients with PC between May 2020 and May 2021. Peptidomic profiles were analyzed using BLOTCHIP^®-mass spectrometry (BLOTCHIP^®-MS) and then compared with those of a propensity score-matched healthy cohort of the same size. PC-specific peptides with significant differences between the two groups were selected and quantitatively measured by selective reaction monitoring (SRM). A discriminant formula to calculate a risk index (RI) was developed based on logistic regression analysis. The RI was validated in newly collected serum samples from 131 patients with PC and 131 healthy controls.

Results: Six PC-specific peptides were selected and an RI formula was established. When the RI cutoff value was set at 0.604, the sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve were 84.0%, 93.4%, 92.7%, 85.3%, and 0.935, respectively. They were similarly high in the validation cohort, at 89.3%, 81.7%, 83.0%, 88.4%, and 0.935, respectively. Furthermore, the sensitivity was relatively high at 76.5% even in the early stages (stage 0/1A).

Conclusions: This novel RI based on serum peptide analysis is useful for screening patients with PC, even in the early stages.

Background: Chronic constipation reduces quality of life and imposes a significant economic burden. The introduction of novel agents in Japan has expanded treatment options. This study aimed to establish a cost-effective treatment strategy, considering clinical utility and patient satisfaction.

Methods: Nine treatment strategies were developed, each consisting of three consecutive treatment options selected from five drugs: magnesium oxide (MgO), lubiprostone, linaclotide, elobixibat, and PEG formulation. A Markov state-transition model was used to estimate costs and outcomes. Effectiveness data were derived from a network meta-analysis of spontaneous bowel movements within 24 h (SBM24) using domestic trial data. Expected costs and quality-adjusted life years (QALYs) were calculated from the healthcare payer's perspective.

Results: In the network meta-analysis, lubiprostone had the highest relative risk for SBM24 (2.36), followed by lactulose (1.84) and elobixibat (1.71). Compared to MgO, the lubiprostone-elobixibat-PEG formulation strategy had additional costs of JPY 8,069.5 and a QALY gain of 0.0710, resulting in an incremental cost-effectiveness ratio (ICER) of JPY 113,709/QALY-well below the willingness-to-pay threshold of JPY 5-6 million/QALY. All strategies had ICERs below JPY 200,000/QALY, indicating favorable cost-effectiveness. Sensitivity analyses confirmed that the lubiprostone-elobixibat-PEG formulation strategy remained the most cost-effective, demonstrating its robustness.

Conclusions: The lubiprostone-elobixibat-PEG formulation strategy showed the most favorable cost-effectiveness profile. In addition, novel treatment options, including lubiprostone, linaclotide, elobixibat, and PEG formulation, were found to be cost-effective compared to MgO. Further research is warranted to confirm these findings and support their application in clinical practice.

Background: The Model for End-Stage Liver Disease 3.0 (MELD 3.0) was developed in the United States to improve prioritization for liver transplantation (LT); however, its utility in Japanese patients with liver cirrhosis (LC) and acute decompensation (AD) remains invalidated.

Methods: We retrospectively analyzed 312 patients with LC and first-time AD admitted to our institution between 2012 and 2022. Prognostic accuracy of MELD 3.0 was evaluated at 90 and 180 days after admission by comparison with other predictive models. Prognoses according to cirrhosis etiology and contributing factors were also examined.

Results: MELD 3.0 demonstrated superior prognostic accuracy at day 180 (C-index: 0.770) compared to the original MELD and MELD Na, although its C-index up to day 90 was comparable to that of MELD and MELD Na. A cut-off value of MELD 3.0 > 20.5 predicted LT or liver-related death at day 180. Patients with primary biliary cholangitis (PBC) had poorer outcomes than non-PBC cases through 180 days and remained an independent risk factor in the Cox proportional hazards model incorporating MELD 3.0. A progressive increase in both MELD 3.0 and total bilirubin from day 0 to day 90 after AD was observed specifically in the PBC group, which may have been associated with the poor prognosis at day 180.

Conclusions: MELD 3.0 was effective in predicting 180-day outcomes in Japanese patients with LC and AD. Progressive bilirubin elevation in PBC may be associated with poor prognosis. These findings suggest that early consideration of LT is warranted in patients with PBC.

Background: Ulcerative colitis (UC) presents with diagnostic challenges due to symptom overlap with other gastrointestinal (GI) disorders. Recent studies identify anti-integrin αvβ6 autoantibodies as a promising biomarker for UC. This meta-analysis aims to evaluate the diagnostic accuracy of anti-integrin αvβ6 antibodies in distinguishing UC from healthy individuals and other GI diseases.

Methods: We conducted a systematic literature search of PubMed, Scopus, and Embase up to February, 2025, following PRISMA guidelines. Studies assessing the diagnostic performance of anti-integrin αvβ6 antibodies in UC patients were included. A bivariate random-effects model was used to pool sensitivity and specificity estimates using STATA. Forest plots and SROC curves were generated. Meta-regression and interaction analyses explored the influence of covariates such as control group type, age group, and geographic region on diagnostic performance. Risk of bias was assessed using tool QUADAS-2. Post hoc analyses were conducted to assess the impact of cut-off thresholds and ELISA platforms on the diagnostic performance of anti-integrin αvβ6 antibodies.

Results: Six studies comprising 3887 participants (1904 UC patients) were included in meta-analysis. The pooled sensitivity and specificity of anti-integrin αvβ6 for UC across all comparator groups were 83% (95% CI: 0.70-0.91) and 93% (95% CI: 0.88-0.97), respectively. Diagnostic performance remained consistent across control types for sensitivity but varied significantly for specificity, especially when Crohn's disease was used as a comparator (81%; 95% CI: 0.75-0.86). Multivariate meta-regression identified patient age, geographic region, and control group type as significant modifiers of specificity. Interaction models further confirmed a combined influence of these factors on diagnostic performance. Post hoc analyses revealed that sensitivity remained stable across thresholds (2SD: 0.65, 3SD: 0.87), while specificity varied significantly depending on cut-off values (2SD: 0.89, 3SD: 0.92) and ELISA methodology (0.92 vs. 0.83).

Conclusions: Our meta-analysis demonstrates that anti-integrin αvβ6 antibodies exhibit high diagnostic accuracy for UC, with consistent sensitivity and specificity. Their performance is influenced by patient demographics and study region, suggesting the need for tailored diagnostic criteria in clinical settings.

Background: The prevalence and characteristics of inflammatory bowel disease-associated spondyloarthritis (IBD-SpA) in Japan are unclear. Moreover, methods for screening SpA among IBD patients have not been established.

Methods: This single-center prospective multidisciplinary study included consecutive patients with IBD, which was newly diagnosed within the past 3 years (early IBD). Board-certified rheumatologists examined the patients for disease history and musculoskeletal manifestations, with imaging studies if needed. Questionnaires assessed patient-reported outcomes and Psoriatic Arthritis Screening and Evaluation (PASE) scores.

Results: We identified 85 eligible patients with early IBD, 22 (25.9%) of whom had Crohn's disease, 63 (74.1%) had ulcerative colitis, and 3 (3.5%) had IBD-SpA diagnosed prior to study enrollment. Rheumatologist evaluations identified additional seven SpA cases, resulting in a total of 10 patients (11.8%) with IBD-SpA (1: axial, 9: peripheral). IBD patients without SpA often presented with back pain (52%) and peripheral joint pain (24%), whereas arthritis, cervical and thoracic pain, and inflammatory back pain were more frequent in IBD-SpA. Newly identified IBD-SpA cases tended to have lower-limb arthritis, dactylitis, and enthesitis, compared with previously diagnosed IBD-SpA cases. For patients with active SpA symptoms in the past 6 months, PASE demonstrated that the area under the receiver operating characteristic curve was 0.87 (95% confidence interval: 0.68, 1.00). The optimal cut-off (33 points) had a sensitivity of 0.88 and specificity of 0.88.

Conclusions: This prospective study found rheumatologist evaluation increased SpA diagnosis and 11.8% of Japanese early IBD patients had IBD-SpA. PASE questionnaires may be effective for screening SpA among IBD patients.

Background: Immunoglobulin G4 (IgG4)-related gastrointestinal diseases (IgG4-GID) are becoming increasingly recognized. However, few cases have been reported, and the disease concept is not yet well established. This study aimed to elucidate the clinical features of IgG4-GID.

Methods: This nationwide multicenter retrospective study collected 37 cases of IgG4-GID, which were classified and analyzed based on the pathological findings and the presence or absence of IgG4-related diseases in other organs. The pathological possibility of IgG4-GID was classified as definite, highly likely, probable, or unlikely based on the presence of typical pathological findings, number of IgG4-positive cells, and adequacy of histological evaluation.

Results: Thirteen patients were classified as unlikely to undergo pathological evaluation. Among the remaining 24 cases, 20 had other organ involvement (pathologically definite, n = 8; highly likely, n = 6; probably, n = 6). The four cases without the involvement of other organs were classified as definite. After defining definite and highly likely cases, 18 cases of IgG4-GID were identified. The most commonly affected organs were the stomach (n = 12) and the duodenum (n = 6), with one case involving both. Endoscopic findings most frequently showed ulcers (n  = 7), followed by submucosal tumor (SMT)-like morphology (n  = 6). Treatments included surgery (n  = 8; SMT-like cases), steroids (n  = 2), and proton pump inhibitors or potassium-competitive acid blockers (n  = 3), with all cases showing improvement.

Conclusions: IgG4-GID exhibits characteristic pathological findings and various endoscopic features. Although many patients respond to treatment, some undergo surgery; thus, increased awareness may help avoid unnecessary surgeries.

Background: Overt hepatic encephalopathy (OHE) is a severe complication of liver cirrhosis. However, data on its incidence, prognostic significance, and associated risk factors in patients without OHE at baseline remain limited.

Methods: A multicenter retrospective cohort study was conducted by reviewing records of hospitalized patients with cirrhosis at three institutions in Japan. OHE was defined as West Haven grade ≥ 2 and its incidence during the follow-up was estimated using the cumulative incidence function. Prognostic factors were assessed using Cox proportional hazards regression analysis, with OHE and hepatocellular carcinoma (HCC) development treated as time-dependent covariates. Independent predictors for OHE development were analyzed using fine-gray proportional hazards regression analysis.

Results: Among 652 patients, the median age was 67 years, and 53% were male. The median model for end-stage liver disease (MELD) score was 9. During a median follow-up period of 3.2 years, 136 patients (21%) developed OHE and 183 patients (28%) died. The cumulative incidence of OHE at 1, 3, and 5 years was 8%, 16%, and 20%, respectively. Multivariable analysis demonstrated that OHE development (hazard ratio [HR], 3.07; 95% confidence interval [CI], 1.99-4.75) was a significant independent prognostic factor, regardless of age, sex, liver functional reserve, and HCC development. Furthermore, multivariable analysis identified lower body mass index, higher MELD score, lower albumin levels, and higher ammonia levels as independent predictors for OHE development.

Conclusions: OHE development is common and increases mortality among patients with cirrhosis. Therefore, close monitoring of high-risk populations is warranted for early management of OHE.