Journal of Gastroenterology and Hepatology最新文献

Background and aim: Sarcopenia and osteoporosis adversely impact the clinical outcomes of patients with chronic liver disease (CLD). The Japan Society of Hepatology (JSH) sarcopenia criteria utilize bioelectrical impedance analysis (BIA) for assessing muscle mass rather than dual-energy X-ray absorptiometry (DXA), which can simultaneously diagnose these comorbidities. We investigated the correlations and interchangeability between the appendicular skeletal muscle mass index (ASMI) values determined using BIA and DXA and evaluated the diagnostic ability of DXA for sarcopenia and osteosarcopenia in patients with CLD.

Methods: This cross-sectional study included 173 patients with CLD. Sarcopenia was defined as low ASMI_BIA according to the JSH and Asian Working Group for Sarcopenia (AWGS) criteria (ASMI_{BIA cutoff}) or low ASMI_DXA according to the AWGS criteria (ASMI_{DXA cutoff}) and low handgrip strength. For women, a provisional cutoff value was set for ASMI_DXA using the ASMI_{BIA cutoff} (ASMI_{DXA-altered cutoff}).

Results: We found that ASMI_BIA and ASMI_DXA were significantly correlated (r = 0.921; P < 0.001). The Bland-Altman plots demonstrated substantial agreement between ASMI_BIA and ASMI_DXA, with a mean difference of 0.0116 kg/m². The prevalence rates of sarcopenia and osteosarcopenia diagnosed using the ASMI_{BIA cutoff} were 26.0% and 17.3%, respectively. The kappa coefficients for the prevalence of sarcopenia and osteosarcopenia were 0.759 and 0.775 between ASMI_{BIA cutoff} and ASMI_{DXA cutoff} and 0.780 and 0.806 between ASMI_{BIA cutoff} and ASMI_{DXA-altered cutoff}, respectively.

Conclusions: The utilization of DXA can facilitate the comprehensive assessment and management of musculoskeletal comorbidities in patients with CLD.

Background and aim: In immunochemical fecal occult blood test (iFOBT) positive subjects, colonoscopy screening can detect colorectal cancers and advanced adenomas, yet most iFOBT-positive subjects find no relevant lower gastrointestinal lesions. Limited data are available on upper gastrointestinal (UGI) cancer risk in iFOBT-positive patients. This study investigated the incidence of UGI malignancies diagnosed within 3 years post-colonoscopy after a positive iFOBT.

Methods: Retrospective analysis of iFOBT-positive patients aged 50-75 years who underwent a colonoscopy at a single institution. All patients with a diagnosis of UGI cancer within 3 years post-colonoscopy were identified by linking with the Queensland Cancer Register. This was used to compare to the geographical population aged 50-74 years based on the Australian Bureau of Statistics and Queensland Cancer Council data.

Results: From 1748 eligible participants, 0.23% (95% confidence interval [CI] 0.06-0.58) were diagnosed with UGI cancer within 3 years post-colonoscopy. This indicates an esophageal cancers rate of 114.42 per 100 000 (95% CI 100.56-298.28) and gastric cancer rate of 57.21 per 100 000 (95% CI 55.76-261.12). Of the patients with a UGI cancer, 75% would have had an unexplained iFOBT. Annual incidence for the same geographic region, ages, and period for the combined esophageal and gastric cancer was 36.08 per 100 000 (95% CI 32.87-39.52).

Conclusions: Among individuals with a positive iFOBT in a bowel cancer screening program, the rates of gastric and esophageal cancers were 2.7 and 7.5 times higher than the general population. Adding gastroscopy to a colonoscopy for iFOBT-positive patients in cancer surveillance programs may be justifiable.

Background and aim: Hepatitis B virus (HBV) reactivation could develop after withdrawal following a finite course of nucleoside analog (NA) therapy, leading to virological and clinical relapses. The genetic heterogeneity in the HBV surface and polymerase genes during finite NA therapy has not been carefully studied.

Methods: Seven chronic HBV-infected patients experiencing relapses following entecavir (ETV; n = 5; Patients 1 to 5) or tenofovir disoproxil fumarate (TDF; n = 2; Patients 6 and 7) withdrawal were included. Sera obtained before treatment and at relapses were retrieved and submitted for DNA extraction and amplicon-specific deep sequencing.

Results: ETV-treated patients had a longer time-to-relapse than that of TDF-treated patients (P = 0.0357). No drug-resistance related polymerase mutation was detected during relapses, except for a low percentage (1.4%) of rtM204I mutation in Patient 1. Two surface truncation mutations (sW216*; 40.9% and sW182*; 4.7%) detected before treatment in two TDF-treated patients (Patients 6 and 7, respectively) were overtaken by the wild types during subsequent drug-withdrawal-related relapses. The simultaneous presence of sG44E (T-cell epitope) and sE164G (B-cell epitope) mutations was associated with failure of HBV e antigen (HBeAg) seroclearance in ETV-treated patients.

Conclusions: In conclusion, HBV genome continues to evolve during the courses of finite antiviral therapies. Pre-existing surface truncation mutations can be overtaken by the wild types after relapses. The sG44E/sE164G mutations are associated with failure of HBeAg seroclearance.

Background and aim: Only a few studies have reported the long-term effects of ustekinumab on pediatric Crohn's disease. Therefore, this study aimed to describe the long-term clinical and endoscopic outcomes of ustekinumab and its safety profile in pediatric-onset Crohn's disease with anti-tumor necrosis factor failure.

Methods: Medical records of patients with pediatric-onset Crohn's disease in whom anti-tumor necrosis factor therapy failed and ustekinumab treatment was initiated from 2017 to 2022 at a Japanese tertiary children's hospital were retrospectively reviewed. The primary outcome was the continuation rates at weeks 8, 52, and 106. The secondary outcomes were the steroid-free remission rates at weeks 8, 52, and 106, changes in the Simple Endoscopic Score for Crohn's Disease, and adverse events during follow-up.

Results: Forty-three patients were enrolled. The median ages at diagnosis and ustekinumab introduction were 9.7 (interquartile range: 6.7-13.0) years and 13.6 (interquartile range: 8.0-16.0) years. The median follow-up period was 136 (interquartile range: 102-172) weeks. The continuation rates were 100%, 91%, and 80% at weeks 8, 52, and 106, respectively. The incidence of discontinuation was 6.2% per patient-year of follow-up. The steroid-free remission rates were 44%, 71%, and 80% at weeks 8, 52, and 106, respectively. The Simple Endoscopic Score for Crohn's Disease of patients in clinical remission at the last follow-up significantly decreased (P < 0.01), and the safety profile was acceptable.

Conclusions: Ustekinumab appeared effective in maintaining long-term clinical remission with endoscopic improvement in pediatric-onset Crohn's disease with anti-tumor necrosis factor failure.

Background and aim: Gel immersion (GI) endoscopy provides a good visual field in endoscopic submucosal dissection (ESD); however, its clinical outcomes are poorly understood. This study aimed to compare the treatment outcomes between esophageal gel immersion endoscopic submucosal dissection (GI-ESD) and conventional ESD (C-ESD) to determine the safety and efficacy of GI-ESD.

Methods: The data of 71 consecutive patients who underwent esophageal ESD between April 2021 and March 2023 at a Japanese tertiary center were retrospectively reviewed. GI was achieved using an additional irrigation tube. The treatment outcomes between the GI-ESD and C-ESD groups were compared using inverse probability of treatment weighting (IPTW) to control for confounding factors.

Results: A total of 75 superficial esophageal epithelial neoplasms (41 in the C-ESD and 34 in the GI-ESD groups) were treated using ESD. The mean procedure time in the GI-ESD group was significantly shorter than that in the C-ESD group (59.2 ± 36.2 vs 85.3 ± 45.7 min, P = 0.008). After IPTW adjustment, the mean procedural times were 62.6 ± 36.6 and 82.9 ± 41.7 min in the GI-ESD and C-ESD groups, respectively (P = 0.037), and the incidence rate of muscle layer damage was 4.2% in the GI-ESD group and 30.6% in the C-ESD group (P = 0.001). In the multivariate analysis, specimen size ≥ 30 mm (odds ratio [OR]: 9.44, 95% confidence interval [CI]: 2.46-36.30, P = 0.001) was positively correlated with longer procedural time (≥ 90 min), whereas GI-ESD (OR: 0.19, 95%CI: 0.05-0.68, P = 0.011) showed a negative association.

Conclusions: Esophageal GI-ESD may be useful in terms of safety and time efficiency. The GI technique could be an option for esophageal ESD.

Background and aim: Differentiating between Crohn's disease (CD) and gastrointestinal tuberculosis (GITB) is challenging. We aimed to evaluate the clinical applicability of an artificial intelligence (AI) model for this purpose.

Methods: The AI model was developed and assessed using an internal dataset comprising 1,132 colonoscopy images of CD and 1,045 colonoscopy images of GITB at a tertiary referral center. Its stand-alone performance was further evaluated in an external dataset comprising 67 colonoscopy images of 17 CD patients and 63 colonoscopy images of 14 GITB patients from other institutions. Additionally, a crossover trial involving three expert endoscopists and three trainee endoscopists compared AI-assisted and unassisted human interpretations.

Results: In the internal dataset, the sensitivity, specificity, and accuracy of the AI model in distinguishing between CD and GITB were 95.3%, 100.0%, and 97.7%, respectively, with an area under the ROC curve of 0.997. In the external dataset, the AI model exhibited a sensitivity, specificity, and accuracy of 77.8%, 85.1%, and 81.5%, respectively, with an area under the ROC curve of 0.877. In the human endoscopist trial, AI assistance increased the pooled accuracy of the six endoscopists from 86.2% to 88.8% (P = 0.010). While AI did not significantly enhance diagnostic accuracy for the experts (96.7% with AI vs 95.6% without, P = 0.360), it significantly improved accuracy for the trainees (81.0% vs 76.7%, P = 0.002).

Conclusions: This AI model shows potential in aiding the accurate differential diagnosis between CD and GITB, particularly benefiting less experienced endoscopists.

Background and aim: M2-polarized tumor-associated macrophages (M2 TAMs) are known to promote cancer progression, and exosomes are crucial mediators of communication within the tumor microenvironment (TME). However, the specific role of exosomes derived from M2 TAMs in pancreatic cancer (PC) progression remains poorly understood. Tyrosine kinase binding protein (TYROBP, also known as DAP12 for DNAX activating protein-12) is a transmembrane signal transduction polypeptide that interacts with immune cell receptors, influencing cellular functions via signal transduction pathways. TYROBP is prominently found in M2 TAMs exosomes, facilitating its transfer to PC cells and suggesting a potential role in PC pathogenesis.

Methods: This study initially confirmed the presence of TYROBP in M2 TAMs exosomes and its transfer to PC cells via exosomes. The impact of TYROBP on PC proliferation, apoptosis, migration, and invasion was investigated. Special attention was given to TYROBP's influence on PC metastasis and its underlying mechanisms, focusing particularly on the CD44/AKT/ERK signaling pathway.

Results: TYROBP expression in PC cells did not significantly affect tumor cell proliferation or apoptosis but demonstrated a notable inhibitory effect on migration and invasion, which was mediated through the CD44/AKT/ERK pathway. Both in vivo and in vitro experiments consistently showed that TYROBP enhanced PC metastasis.

Conclusions: This study elucidates that TYROBP plays a direct role in promoting PC metastasis through its association with M2 TAMs polarization. Therefore, TYROBP represents a potential novel therapeutic target for interventions aimed at combatting PC progression.

Background and aim: Tofacitinib and aminosalicylic acid (5-ASA) are commonly used to treat ulcerative colitis (UC). However, evidence on the effect of concomitant 5-ASA use in patients receiving tofacitinib is limited. This study investigated the effects of 5-ASA combined with tofacitinib in UC patients.

Methods: This retrospective cohort study used data from the Medical Data Vision database, including patients with UC treated with tofacitinib from May 2018 to April 2022. Patients were grouped according to tofacitinib dosage and assessed for the efficacy of concomitant 5-ASA use. The primary endpoint was clinical relapse.

Results: A total of 1213 patients with UC were included in the analysis, with 416 in the 5 mg BID group and 797 in the 10 mg BID group. In the 5 mg BID group, the cumulative relapse-free rate was significantly higher in patients receiving concomitant 5-ASA (P < 0.0001). Multivariate Cox regression analysis confirmed that concomitant 5-ASA use significantly reduced the risk of clinical relapse (adjusted hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.31-0.70). In the 10 mg BID group, no significant difference was noted in the cumulative relapse-free rate between patients treated with and without 5-ASA (P = 0.445). Similarly, multivariate Cox regression analysis indicated that concomitant 5-ASA use did not significantly affect relapse risk (adjusted HR, 0.97; 95% CI, 0.71-1.32).

Conclusions: Concomitant 5-ASA use reduced the risk of relapse in patients on 5 mg tofacitinib BID, suggesting benefits at lower doses. However, no significant benefit was observed with 5-ASA use in those 10 mg tofacitinib BID.

Background and aim: The risk of developing a second primary malignancy differs among colorectal cancer patients in different age groups. This study aimed to investigate the differences in prognosis and clinicopathological features of patients with early-onset colorectal cancer and late-onset colorectal cancer who developed second primary malignancies.

Methods: The study included 15 489 patients who underwent surgery for colorectal cancer at Fudan University Shanghai Cancer Center between January 2008 and December 2018. Data pertaining to these patients were derived from the database.

Results: A total of 680 (4.5%) patients subsequently developed a second primary malignancy. Considering death as a competing event, the 10-year cumulative risk of second primary malignancy for early-onset colorectal cancer was 5.3%, compared with 7.3% for late-onset colorectal cancer. Cox analysis showed that late-onset colorectal cancer, colon cancer, smaller tumor size, and fewer tumor nodules without residual lymph node structure, chemotherapy, and radiotherapy were independent risk factors for second primary malignancy. In our patient cohort, early-onset colorectal cancer was associated with better prognosis compared to late-onset colorectal cancer, for both overall survival and second primary malignancy-free survival. In addition, there was insufficient evidence that early-onset colorectal cancer also affected prognosis after the occurrence of second primary malignancies.

Conclusions: The risk of early-onset colorectal cancer subsequently developing second primary malignancy was significantly lower than late-onset colorectal cancer, and the second primary malignancies of early-onset colorectal cancer were more likely to be colorectal cancer. Overall survival and second primary malignancy-free survival of early-onset colorectal cancer were consistently better than late-onset colorectal cancer.