BMJ Open Gastroenterology最新文献

Objective: Appendiceal adenocarcinoma is a rare cancer with very limited therapeutic options. We aimed to determine whether molecular profiling of advanced appendiceal adenocancer can identify actionable therapeutic alterations.

Methods: We retrospectively analysed cohorts from two large German precision oncology programmes. Patient records and pathology reports from 19 patients with advanced appendiceal adenocarcinoma who were enrolled between 2015 and 2021 were included in this study. We report the molecular features, the resulting molecular tumour board recommendations and their clinical implementation.

Results: In 95% of the tumours, at least one potentially actionable alteration was identified, including mutations in ATM, PIK3CA and AKT1. An elevated tumour mutational burden was identified in 26% of the tumours. A total of 74% of all patients received a molecularly driven treatment recommendation, of which 2 (11%) received the recommended therapy.

Conclusion: Molecular profiling of appendiceal adenocarcinomas revealed potentially actionable alterations in a number of cases.

Objective: Intestinal failure in advanced malignancy is most commonly due to mechanical bowel obstruction. Palliative home parenteral nutrition (HPN) is an option for such patients to meet their nutritional needs. However, there are limited data on overall survival and predictive factors. This study aimed to evaluate the survival of patients receiving palliative HPN and the impact of patient factors on survival.

Methods: This is a single-centre retrospective observational study of patients referred for palliative HPN from 1 January 2020 to 19 November 2024 at the Cambridge University Hospitals NHS Foundation Trust. Demographic, nutritional and medical data were analysed. Survival rates were compared using Kaplan-Meier curves and Cox regression.

Results: 84 patients were referred and 77 were discharged with HPN (median age was 60.9 years (IQR: 51.3-70.4), female 77%). 78% of the underlying primary malignancies were gynaecological and gastrointestinal. Malignant bowel obstruction was the main indication for HPN (86%). Eastern Cooperative Oncology Group performance status (PS) scores were ≤2 in 82% of patients and 75% had an estimated prognosis of >3 months. Median survival was 58 days (IQR 31-108) with a 3-month mortality of 69%. There was no statistical difference in survival by PS, estimated prognosis, underlying malignancy or modified Glasgow Prognostic Score (mGPS).

Conclusions: The overall survival in our study is modest. PS, prognosis, mGPS or tumour type did not show a significant impact on survival. This highlights the challenges in artificial nutrition and emphasises the role of a multidisciplinary team in the care of these patients.

Objective: Deficiencies have been highlighted in acute hospital care for alcohol-related liver disease (ARLD). Such problems may be worse at weekends (WEs). Increased 30-day mortality for WE admissions has been reported for several acute conditions, but data for ARLD are limited. We aimed to compare patient and pathway characteristics between WE and weekday (WD) admissions and investigate the 'weekend effect' on mortality.

Methods: Retrospective cohort study (2008-2018) using linked electronic databases (Hospital Episode Statistics-Clinical Practice Research Datalink and death registration) including 17 575 first emergency admissions identified using the Liverpool ARLD algorithm.

Exposure: WE admission (Saturday or Sunday).

Main outcome: all-cause death within 30 days. Covariates included socio-demographic characteristics, pathway characteristics (pre-admission contacts and admission method) and markers of severity (recorded stage of liver disease, ascites and varices, comorbidity). Alternative risk-adjustment methods were used, including standard regression and propensity-weighted analysis (Inverse Probability of Treatment Weighting).

Results: 3249 admissions (18.5%) were at WE. Unadjusted 30-day mortality was significantly higher for WE versus WD (17.1% vs 15.5%, p=0.018). All models demonstrated increased odds of death for WE admissions with adjusted ORs ranging from 1.15 to 1.23 (relative risk of 1.12-1.19). Causes of death did not vary by admission day and effect was consistent across subgroups. Findings were robust to sensitivity analyses restricting the cohort to patients admitted directly from Accident and Emergency department (A&E), or cirrhosis or ascites but not varices.

Conclusion: First ARLD admissions at the WE experienced a 12-19% increase in 30-day mortality risk compared with WD. Although residual confounding cannot be excluded, this suggests the possibility of avoidable mortality among those hospitalised at WEs. Services should be alert to risks of WE effects when planning care.

Objective: Current patient-reported outcome measures (PROMs) for chronic constipation (CC) have been predominantly developed for Western populations, often neglecting cultural factors critical to Asian contexts. This study aimed to psychometrically validate the Asian Constipation Assessment Initiative Questionnaire (ACAIQ), codesigned with patients experiencing CC and clinicians in Singapore, and examine the effect of constipation awareness on symptom reporting.

Methods: A cross-sectional study enrolled 259 participants with CC (Rome IV criteria) and 153 healthy controls between 9 December 2022 and 19 March 2024. Participants completed the ACAIQ alongside established PROMs. Structural validity, internal consistency, test-retest reliability and criterion validity were evaluated following Consensus-based Standards for the Selection of Health Measurement Instruments guidelines. The influence of constipation awareness on symptom reporting and Rome IV criteria was analysed using non-parametric statistical tests.

Results: ACAIQ-SYM (symptom severity scale) demonstrated strong structural validity (comparative fit index=0.968, Tucker-Lewis Index=0.958, root mean square error of approximation=0.06), internal consistency and reproducibility (α=0.88, intraclass correlation coefficient≥0.70). However, the ACAIQ-QoL (quality of life scale) exhibited structural inconsistencies, necessitating further refinement. Aware participants reported more severe symptoms than unaware and controls (p<0.05). Notably, 71.4% of participants with CC were unaware of their condition, underscoring the importance of constipation awareness in symptom perception and reporting.

Conclusion: ACAIQ-SYM is a valid tool for assessing constipation symptoms in Asian populations. The significant impact of awareness on symptom reporting highlights the need for patient education. Further refinement of ACAIQ-QoL is necessary to ensure a comprehensive evaluation of QoL. Once optimised, ACAIQ could improve digital health platforms, patient-clinician engagement and personalised CC management strategies.

Objective: This study aimed to explore the lived experiences and coping strategies of patients with short bowel syndrome (SBS) prescribed teduglutide and weaning off home parenteral nutrition (HPN), and to compare the quality of life (QOL) of these patients to patients with SBS but not prescribed teduglutide.

Methods: A qualitative study was conducted, with patients recruited from a specialist HPN clinic. Participants completed handwritten semi-structured daily diaries for 6 weeks and a validated Home Parenteral Nutrition-Quality of Life (HPN-QOL) paper-based questionnaire as part of what aimed to be a mixed methods cross-tracks study. Participants were age-matched with patients with SBS receiving HPN but not prescribed teduglutide, and these 'controls' also completed the HPN-QOL questionnaire. Data analysis involved qualitative analysis of diary entries using grounded theory methodology and descriptive analysis of HPN-QOL questionnaire responses.

Results: Five participants completed the study and were matched with four 'controls'. All participants and 'controls' reported a high QOL with no differences observed between patients prescribed and not prescribed teduglutide. Qualitative analysis revealed that participants engaged in iterative cycles of problem-focused action and emotion-focused coping strategies to manage their condition and wean off parenteral nutrition (PN). Key subthemes included polyphagia and pleomorphism in diet, fatigue-related emotional distress and positive reframing using an objective scientific lens. Decisional regret was absent, participants agreed that treatment with teduglutide was the right choice for them, despite its challenges. Their goal of independence from PN was the main motivating factor.

Conclusion: This study provides valuable insights into the lived experiences and coping strategies of patients with SBS prescribed teduglutide to wean off PN. The findings underscore the importance of healthcare teams understanding these everyday challenges to facilitate shared decision-making and tailor care plans. Further research is needed to explore the long-term impact of teduglutide on QOL, including the validation of tools to screen for fatigue-related emotional distress and the development of targeted interventions to support patients during the weaning process.

Objective: Fontan-associated liver disease (FALD) results from haemodynamic changes following the Fontan procedure for congenital heart disease and is associated with poorer outcomes. The prevalence of Fontan is rising due to improved survival; however, little is known about predictors of advanced liver fibrosis in adult patients. This study aimed to determine the accuracy of non-invasive fibrosis assessment tools (NIT) in predicting histologically confirmed advanced liver fibrosis in an adult Fontan cohort attending Mater Misericordiae University Hospital.

Methods: Patient demographics, congenital cardiac variables and fibrosis biomarkers were recorded including liver stiffness measurement (LSM) via transient elastography, Fibrosis-4 (FIB-4) and Aspartate aminotransferase-to-Platelet Ratio Index (APRI) scores. Biopsies, taken between 2017 and 2024, were staged using the congestive hepatic fibrosis score. Analysis was performed using SPSS.

Results: 71 patients (58% male) were included. The median age was 25 years. 62% had histological advanced fibrosis. There were no significant bleeding events post biopsy. Overall, advanced fibrosis was associated with a closed Fontan fenestration (p=0.022) and higher LSM, although with a weak correlation (p=0.04, r=0.25, area under the curve (AUC) 0.65), but not with APRI or FIB-4. There was no difference in rates of advanced fibrosis between sex (p=0.84). In females, higher APRI was associated with advanced fibrosis (p=0.045, r=0.41, AUC 0.73).

Conclusions: The majority of Fontan patients have advanced liver fibrosis in their third decade. A patent Fontan fenestration appears to reduce the risk of advanced fibrosis. Despite an association with higher LSM, there was no cut-off which could negate the need for biopsy in a significant population. Our data suggest that the discriminatory ability of NIT may vary according to sex. Liver biopsy is safe and remains the only method of reliably diagnosing advanced fibrosis in FALD.

Objective: Recent evidence supports diagnosing coeliac disease without biopsy in patients with significantly elevated tissue transglutaminase (IgA-tTG) antibodies. However, the implementation of this no-biopsy approach relies on accurate and consistent serological testing across laboratories. In this nationwide survey, we aimed to evaluate the availability and variability of coeliac disease testing across the UK.

Methods: We conducted a cross-sectional telephone survey of biomedical scientists and laboratory managers from National Health Service trusts and health boards across England, Wales, Scotland, and Northern Ireland. Data collected included assay types, reporting methods, upper limit of normal (ULN) thresholds, turnaround times, total IgA testing, and anti-endomysial antibodies (EMAs) availability.

Results: A total of 356 sites were approached, with a 96% response rate (n=342). Of responding sites, 177 performed coeliac serology tests in-house, while 165 transferred samples externally. Among sites performing tests, 12 different IgA-tTG assays were identified, with considerable variability in ULN thresholds ranging from 3 to 30 IU/mL, even within laboratories using the same assays. The median turnaround time for IgA-tTG results was 7 days (range 1-21 days). Only 43% of laboratories routinely measured total IgA when IgA-tTG was requested. EMA testing was available in 83% of laboratories.

Conclusion: Significant variability exists in coeliac serology testing across UK laboratories which poses a challenge for the implementation of the no-biopsy approach in clinical practice. Efforts to standardise serological testing are urgently needed. Until such standardisation is achieved, local assay validation remains critical.

Objective: Alcohol-related liver disease (ArLD) is a leading cause of liver-related mortality, but affects a minority of people with alcohol use disorder (AUD). Of people with AUD, only those with ArLD require hepatologist input, necessitating case stratification. However, many are referred with established cirrhosis, when opportunities for intervention are limited. We report the evaluation of a novel primary care pathway using the enhanced liver fibrosis (ELF) test for early detection and stratification of ArLD patients.

Methods: The ELF alcohol pathway (EAP) was established in January 2020 and evaluated in May 2023. General practitioner referrals to a single liver centre using the EAP were compared with standard care (SC) referrals. The presence of steatosis constituted an 'appropriate' referral. The prevalence of structural ArLD and each stage of fibrosis was assessed, with liver status ascertained through electronic patient records.

Results: The EAP was followed by 121 patients. Unnecessary referral (ELF<9.8) was avoided for 24.8% (n=30), with the 91 remaining EAP referrals compared with 197 contemporaneous SC referrals. Most referrals were deemed appropriate (97.5% vs 92.3% for SC and EAP, respectively), but significantly more SC referrals had advanced fibrosis (OR 2.68 (1.50 to 4.93); p<0.001), cirrhosis (OR 6.58 (2.84 to 17.79); p<0.0001) or decompensated cirrhosis (10.7% vs 0%; p<0.001).

Conclusion: Using the EAP facilitated earlier detection of ArLD, with 8% of EAP referrals having established cirrhosis versus 35.5% of SC referrals. Unnecessary specialist referral was avoided for one-quarter of those assessed on the EAP. Pathway uptake was impacted by poor dissemination during the COVID-19 pandemic. Better implementation is warranted.

Objective: Perianal fistulas in Crohn's disease (CD) are associated with a high burden of illness and their treatment is challenging. Recent data indicate promising short-term efficacy of bone marrow-derived mesenchymal stromal cell (bmMSC) therapy. The aim of this case series is to gather more information on the long-term effectiveness and safety.

Methods: Between 2013 and 2017, bmMSCs were administered under compassionate use to patients at a university hospital in Germany, as no stem cell therapy was approved at the time. Inclusion criteria were inactive CD (Harvey-Bradshaw Index <5) without proctitis, at least one treatment-refractory perianal fistula (with or without rectovaginal additional fistulas) and prior tumour necrosis factor-alpha inhibitor and/or surgical exposure. After curettage of the fistula tract, patients received repeated intrafistular injections with up to 300 million bmMSCs. We retrospectively analysed patient records to assess disease course, clinical fistula remission and radiological activity using the modified van Assche index.

Results: Six female patients with a total of 13 fistulas (9 trans-sphincteric, 2 extrasphincteric and 2 rectovaginal) underwent bmMSC application. Median radiological and clinical long-term follow-up was 80 months (range 44-98 months) after first local bmMSC injection. 8 of 13 fistulas (62%) exhibited complete closure. For rectovaginal fistulas, long-term remission (98 months) was 50% (1 of 2). Pelvic MRI showed a decrease in modified Van Assche index from baseline to long-term follow-up. No immediate adverse events related to bmMSC injections were observed. One patient was diagnosed with a local adenocarcinoma of the rectum 106 months after first bmMSC injection. MRI control 11 months prior showed complete fistula remission. The tumour exhibited a female karyotype, while bmMSC had been derived from a male volunteer.

Conclusion: In this analysis, 62% of complex perianal and 50% of rectovaginal fistulas showed long-term remission up to 8 years post-bmMSC therapy. Further real-world data are needed.

Introduction: Cholangiocarcinoma (CCA) carries a high risk of recurrence even after curative resection. Capecitabine is standard adjuvant therapy, but recurrence rates remain significant, particularly in high-risk patients. Immunotherapy has shown promise in advanced CCA, prompting investigation into its role in earlier settings.

Methods and analysis: This multicentre, randomised, open-label phase II trial will compare adjuvant adebrelimab plus capecitabine versus capecitabine alone in patients with high-risk resected CCA. The study is being conducted at four tertiary hospitals in Jiangsu Province, China. Eligible patients will be randomised 1:1. The primary endpoint is 1-year recurrence-free survival rate (1y-RFS rate). Secondary endpoints are overall survival, RFS and safety. Exploratory endpoints are circulating tumour DNA (ctDNA)-based MRD assessment.

Ethics and dissemination: The study is approved by the Institutional Review Board of Jiangsu Provincial People's Hospital (2024-SR571). Informed consent will be obtained from all participants. The findings will be published in peer-reviewed journals and presented at scientific conferences.

Trial registration number: NCT06607276.