Digestive and Liver Disease最新文献

Background: Early life factors for inflammatory bowel disease are likely to impact the gut microbiota.

Aim: We investigated the associations between early exposures and inflammatory bowel disease.

Methods: This case-control study was nested within the CO·MMUNITY cohort. Cases of Crohn's disease (CD) and ulcerative colitis (UC) were identified using validated algorithms. All cases and randomly selected controls were invited to complete a questionnaire including early life exposures. Analyses were conducted by logistic regression and causal mediation (direct/indirect effects for passive/active smoking).

Results: Early introduction of solid foods at 3-6 months tended to increase CD risk compared to later introduction (>6 months): OR = 1.23; 95 % CI: 0.96-1.56, but not of UC. Exclusive breastfeeding tended to decrease the risk of CD (OR = 0.77; 95 % CI: 0.55-1.08), less so for UC. Antibiotics tended to decrease CD (OR = 0.89; 95 % CI: 0.74-1.07) and UC (OR = 0.88; 95 % CI: 0.71-1.09). No association was found between pets and CD or UC. Passive smoking increased CD risk (OR = 1.23; 95 % CI: 1.00-1.51), 20 % of which was mediated by active smoking, but not UC.

Conclusion: Differences were noticed in early risk factors for CD and UC. The impact of passive smoking was largely independent of active smoking, highlighting its importance for prevention.

Background: Catenin beta 1 (CTNNB1) mutations are one of the most common mutations involved in hepatocellular carcinoma (HCC) progression. However, the association between CTNNB1 mutations and HCC remains controversial.

Methods: Five tumor samples with wild-type CTNNB1 and three tumor samples with CTNNB1 mutations were collected from patients with HCC for whole transcriptome sequencing. Selected ncRNAs and mRNAs were validated by qPCR in 48 HCC tumors. Selected ncRNA regulatory axes were verified in HCC cells by transfecting mimics and inhibitors of miRNA.

Results: A network of differentially expressed (DE) lncRNA/circRNA-miRNA-mRNA was constructed to explore the effects of CTNNB1 mutations on ncRNA regulation. TXNRD1, CES1, MATN2, SERPINA5, lncRNA STAT4-210, hsa_circ_0007824, hsa_circ_0008234, hsa-miR-205-5p and hsa-miR-199a-5p were verified at the RNA expression level to validate the sequencing results. The down-up-down axes GLIS3-209/circ_0085440-miR-205-5p-GHRHR and WNK2-213-miR-3940-3p-LY6E were verified at the expression level, and proved to inhibit and promote cell proliferation, respectively.

Conclusion: This study demonstrated CTNNB1 mutations associated ncRNA regulatory axes playing different roles in HCC cell proliferation, providing novel insights into the controversial role of CTNNB1 in HCC.

Background: Anti-glycoprotein 2 (anti-GP2) IgA and antineutrophil-cytoplasmic antibodies to proteinase 3 (PR3-ANCA) have been reported as predictive markers of cholangiocarcinoma (CCA) in patients with primary sclerosing cholangitis (PSC), but their prevalence in CCA patients without PSC remains unclear.

Methods: This study involved Asian discovery (n = 118) and European validation (n = 38) cohorts of CCA patients without PSC, alongside 49 Asian and 82 European pancreatic ductal adenocarcinoma (PDAC) patients, 21 with benign pancreatic neoplasms (BPN) and 45 with hepatocellular carcinoma (HCC), and 157 healthy controls (HC) from Asia and Europe. We analyzed the prevalence of PR3-ANCA, IgA and IgG against GP2₁ and GP2₄, and the CA19-9 levels.

Results: Anti-GP2₁ IgA was the most prevalent in both CCA cohorts (discovery: 55.1 %; validation: 42.1 %) and significantly higher than in other groups except PDAC (all p < 0.05). It demonstrated the best diagnostic performance in distinguishing CCA from disease controls and HC, outperforming tumor markers. No significant correlation was found between anti-GP2₁ IgA levels and CA19-9 levels.

Conclusion: Our findings show that anti-GP2₁ IgA revealing the loss of mucosal tolerance is a potential novel diagnostic biomarker for CCA.

Background: Autoimmune gastritis (AIG) leads to increased gastrin (G) levels due to hypo-achlorhydria, providing proliferative stimuli on the gastric mucosa.

Aims: To evaluate the incidence and characteristics of gastric polyps in AIG patients across six tertiary centers in Italy.

Methods: A multicentric, cross-sectional study enrolled patients with AIG diagnosed from January 2000 to June 2023, who underwent at least one endoscopy. Data on demographics, clinical history, biochemical profiles, and endoscopic and histopathological findings were systematically collected.

Results: Among 612 AIG patients followed for a median of 4 years, 222 (36.3 %) developed at least one gastric polyp. Of these, 214 were non-endocrine lesions detected in 162 patients, including 151 inflammatory (70.5 %), 29 adenomatous (13.6 %), 18 fundic gland polyps (8.4 %), 13 adenocarcinomas (6.1 %), and one MALT lymphoma. Additionally, 108 patients had gastric neuroendocrine neoplasms (gNENs), with 48 also having non-endocrine polyps. Older age and higher gastrin and chromogranin A levels were associated with polyp occurrence. No differences in OLGA/OLGIM stages or Helicobacter pylori status were noted among patients with and without lesions.

Conclusion: This large multicentric study underscores the substantial occurrence of gastric polyps in AIG patients, including notable rates of gNENs and adenocarcinomas, emphasizing the importance of proactive endoscopic surveillance and histopathological examination for effective management.

Introduction: Cisplatin, nab-paclitaxel, capecitabine, and gemcitabine (PAXG) regimen activity was assessed in a single institution phase II trial (PACT-19) on pancreatic ductal adenocarcinoma (PDAC). The PACT-31 study explored the external validity of PACT-19 results.

Materials and methods: Patients aged ≥18 and ≤75 years with KPS ≥70, and PDAC diagnosis receiving PAXG in the participating institutions were eligible and categorized as follows: A) PACT-19; B) PACT-31-HSR; C) PACT-31-non-HSR. With a sample of 175 patients, assuming a target 1-year overall survival of 60 % for metastatic and of 80 % for non-metastatic patients, the trial will be considered successful with the 1-year OS falling into the 95 % CI.

Results: Data from 68 PACT-19 and 168 PACT-31 patients were retrieved. After 124 events, 1yOS was 52.5 % (95 %CI: 44.6-60.4 %) for metastatic and 80.5 % (95 %CI: 71.9-89.1 %) for non-metastatic patients. Survival overlapped between PACT-19 and PACT-31-HSR (median 17.6 and 17.4 months, p = 0.21) and was significantly shorter in PACT-31-non-HSR (median 11.3 months; p = 0.03). Differences of dose-intensity, use of maintenance therapy, and treatment after progression between PACT-31-HSR and non-HSR were evidenced.

Discussion: PACT-19 results have external validity. The outcome difference between HSR and non-HSR centers endorses the need of creating a hub-and-spoke network aimed at sharing the expertise on rare-diseases.

Background and aim: Suboptimal disease control (SDC) and its contributing factors in IBD according to STRIDE-II criteria is unclear. IBD-PODCAST was a non-interventional, international, multicenter real-world study to assess this.

Methods: Data from the Italian IBD cohort (N=220) are presented here. Participants aged ≥19 with confirmed IBD diagnosis of ≥1 year were consecutively enrolled. A retrospective chart review and cross-sectional assessment by physicians and patients within the past 12 months were performed. SDC or optimal disease control was assessed using adapted STRIDE-II criteria.

Results: At the index date, 53.4 % of 116 CD patients and 49.0 % of 104 UC patients had SDC, mainly attributed to a Short Inflammatory Bowel Disease Questionnaire score <50, failure to achieve endoscopic remission, and the presence of active extra-intestinal manifestations in both diseases. Disease monitoring with imaging and/or endoscopy during the previous year was conducted in ∼50 % of patients, with endoscopy performed in ∼40 %. Potential therapeutic adjustments were reported for half of the patients.

Conclusions: This study highlights SDC in a significant portion of IBD Italian patients. These results emphasize the need for more proactive management strategies in both CD and UC patients.

Background: Factors associated with the risk of pancreatic adenocarcinoma (PDAC) may play a role in the development and progression of Intraductal Papillary Mucinous Neoplasms (IPMNs). However, data are limited.

Aim: To compare exposome factors in three groups of patients with "high or low-risk" IPMNs, as assessed at diagnosis and during a 24-months follow-up, and with PDAC.

Methods: Patients were matched (same sex, age ±5) 1:1. Exposure variables were compared across groups using Kruskal-Wallis, ANOVA, or Chi-square tests with Bonferroni correction.

Results: A total of 151 patients were enrolled in each of the three groups (453 overall). The proportion of current smokers was progressively higher in "low-risk", "high-risk" IPMNs and PDAC patients (8.1 %, 11.2 %, 23.3 %; p = 0.0002). The three groups did not differ in terms of ever or heavy smoking, BMI, history of diabetes, cancer, cholecystectomy or chronic pancreatitis, use of statins or aspirin, and family history of cancer. A history of peptic ulcer was more common in PDAC (7.2 %) than in either "low-risk" (2.0 %) or "high-risk" (2.6%) IPMNs (p = 0.02, not significant after Bonferroni correction).

Conclusion: Active smoking seems associated with the progression of IPMNs to malignancy, and cessation of active smoking might be advised in patients with IPMN.

Background: The prognostic value and clinical relevance of tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) in esophageal squamous cell carcinoma (ESCC) remain unclear.

Aims: To investigate the prognostic value and functional involvement of TILs in ESCC.

Methods: We included 40 patients across different stages of ESCC from Xinjiang. Multiplex fluorescent immunohistochemistry characterized TILs and TAMs. TILs in different tumor regions were quantified and correlated with overall survival (OS) using log-rank test and Cox regression analyses.

Results: Invasive ESCC exhibited increased CD4 T cells and Tregs compared to carcinoma in situ, with a higher Tregs/CD4 T cells ratio (p < 0.05). TAMs, primarily in stromal regions, were significantly associated with Foxp3+ cells (p < 0.05). Higher infiltration of stromal TAMs and a higher CD4/CD8 T cells ratio correlated with poorer OS, while a higher CD8 T/Foxp3+ cells ratio indicated better survival. Multivariate Cox analysis revealed TNM stage, tumor length, and stromal CD4/CD8 T cells ratio as independent prognostic factors (p < 0.05). An immune prognostic risk score-based nomogram was constructed to predict patient outcomes.

Conclusions: The spatial distribution and abundance of TILs significantly correlated with prognosis, providing a useful immune classification for ESCC.

Background and aims: Bevacizumab-based chemotherapy is a recommended first-line treatment for metastatic colorectal cancer (mCRC). Robust biomarkers with clinical practice applicability have not been identified for patients with this treatment. We aimed to evaluate the prognostic yield of serum mid-infrared spectroscopy (MIRS) on patients receiving first-line bevacizumab-based chemotherapy for mCRC.

Methods: We conducted an ancillary analysis from a multicentre prospective study (NCT00489697). All baseline serums were screened by attenuated total reflection method. Principal component analysis and unsupervised k-mean partitioning methods were performed blinded to all patients' data. Endpoints were progression-free survival (PFS) and overall survival (OS).

Results: From the 108 included patients, MIRS discriminated two prognostic groups. First group patients had significantly lower body mass index (p = 0.026) and albumin levels (p < 0.001), and higher levels of angiogenic markers, lactate dehydrogenase and carcinoembryonic antigen (p < 0.001). In univariate analysis, their OS and PFS were shorter with respective medians: 17.6 vs 27.9 months (p = 0.02) and 8.7 vs 11.3 months (p = 0.03). In multivariate analysis, PFS was significantly shorter (HR = 1.74, p = 0.025) with a similar trend for OS (HR = 1.69, p = 0.061).

Conclusion: By metabolomic fingerprinting, MIRS proves to be a promising prognostic tool for patients receiving first-line bevacizumab-based chemotherapy for mCRC.

Background: Locally advanced rectal cancer can cause severe symptomatic pelvic morbidity such as pain, haemorrhage or bowel obstruction for frail or metastatic patients, which are often unfit to undergo surgery or intense systemic treatment. The most frequent radiation schedule is 25 Gy/ 5f but the optimal dose is yet to determine. Our aim was to conduct a systematic review on the efficacy and toxicity of the published radiation schedules of palliative rectal cancer.

Methods: Systematic literature of the Medline, Embase and Cochrane library databases were performed throughout the year 2023. Published articles on palliative external beam radiation therapy (EBRT) for locally advanced or metastatic rectal cancer reporting on symptom palliation, overall survival (OS) and quality of life (QOL) were eligible for inclusion.

Results: Thirteen studies were included, five of them were prospective studies. There were large variations in radiation schedules, associated chemotherapy and palliative care. Pooled overall symptomatic response rate was 71 %, while response rates were respectively 90 %, 85 %, and 84 % for pain, bleeding, and pelvic symptoms. Acute toxicities were mostly mild genitourinary or gastrointestinal.

Conclusions: Short course palliative radiation for LARC for frail or metastatic patients is efficient for symptom palliation with few adverse effects. A short course EBRT with an integrated IMRT boost on the tumoral volume could be of interest.