Gastroenterology Report最新文献

We report on an infant girl with biliary atresia, who, at the age of 6 months, received a living-related liver transplantation (LRLT), (segments II/III) from her 37-year-old healthy mother. Five months after LRLT, the child developed skin lesions on sunlight exposed skin areas. Based on plasma fluorescence scanning, biochemical findings and DNA testing variegate porphyria (VP) was diagnosed in the girl. In this remarkable case hepatic heme synthesis was induced in the transplanted liver through medication (metamizole), stress and infection (cholangitis), unmasking previously undiscovered partial enzyme deficiency of PPOX. LRLT with subsequent manifestation of heterozygous VP in very early childhood has not been described hitherto. Our report will increase awareness of "rare risks" for "rare diseases" in liver transplantation.

Background: The prognosis of a pancreatic neuroendocrine neoplasm (pNEN) is closely correlated with histological grade. While the role of tomoelastography in predicting tumor grades has been explored in various cancers, evidence regarding its association with the histological grade and clinical features of pNENs remains limited. This study aimed to investigate the association between tomoelastographic parameters and the histological grade and key clinical characteristics of pNENs.

Methods: A retrospective study was conducted on 62 patients with pathologically confirmed pNENs, all of whom underwent tomoelastography prior to surgery without receiving neoadjuvant treatment. Patients were categorized into three groups: G1 (n = 28), G2 (n = 30), and G3/neuroendocrine carcinoma (NEC) (n = 4). The relationship between the tomoelastography parameters and clinicopathological characteristics was analysed by using the Kruskal-Wallis test, Spearman correlation, and ordinal logistic regression. Receiver-operating characteristic curves were used for evaluating the diagnostic performance of tomoelastography.

Results: The shear wave speed (c), representing stiffness in tomoelastography, increased with tumor grade (1.63 m/s for G1 vs 2.23 m/s for G2 vs 2.53 m/s for G3&NEC, P < 0.001). Parameter c was positively correlated with the tumor size (r = 0.59, P < 0.001) and Ki67 index (r = 0.44, P < 0.001), and was notably higher in lesions with distant or regional lymph node metastases than in those without metastases. Identified as a hazardous factor for tumor grade (odds ratio = 3.92, 95% confidential interval [CI]: 1.88-8.16), c showed good performance in discriminating between G1 and G2 (area under the curve = 0.81, 95% CI: 0.70-0.93, P < 0.001).

Conclusion: Tomoelastography offers a promising quantitative tool for assessing the histological grade of pNENs and identifying more aggressive tumor behavior via increased tissue stiffness.

Background: 5-fluorouracil (5-FU)-based chemotherapy remains the backbone of metastatic colorectal cancer (CRC) treatment, although therapeutic resistance limits long-term benefit. Combination with bevacizumab improves outcomes in some patients, but biomarkers capable of predicting benefit are lacking. Notch signalling and altered expression of its ligand Jagged1 (JAG1) have been implicated in CRC progression, yet their relevance in bevacizumab-treated patients and their regulation by 5-FU remain unclear.

Methods: JAG1 protein levels were quantified in tumour samples from patients with metastatic CRC (n = 60) by using enzyme-linked immunosorbent assay and correlated with clinical outcomes. In vitro experiments using HCT15 and SW480 CRC cell lines were used to assess the effects of combining 5-FU and the γ-secretase inhibitor N-[N-(3,5-difluorophenacetyl-l-alanyl)]-S-phenylglycine t-butyl ester (DAPT) on proliferation using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Notch pathway, stemness, epithelial-mesenchymal transition (EMT), and apoptosis markers were assessed by using quantitative PCR and/or Western blotting. The angiogenic capacity of the secretome was examined by using tube-formation assays.

Results: Among patients receiving bevacizumab, those with low tumour JAG1 expression exhibited longer progression-free survival and time to progression than patients with high JAG1 expression. In vitro, DAPT plus 5-FU synergistically reduced CRC-cell viability, enhanced apoptosis and autophagy, reduced the expression of stemness and EMT-related genes, and impaired tube formation. Soluble JAG1 was detected in conditioned media, with higher levels following combination treatment in HCT15 cells.

Conclusions: High tumour JAG1 expression identifies metastatic CRC patients with poorer outcomes when treated with a bevacizumab-containing regimen, supporting its potential as a prognostic biomarker. Mechanistically, Notch inhibition enhances the antitumour effects of 5-FU, suggesting that its combination with γ-secretase inhibitors may improve therapeutic efficacy in CRC.

Gastric or gastroesophageal junction cancer (GC/GEJC) ranks as the fifth leading cause of cancer-related mortality worldwide. Curative-intent surgery remains the cornerstone of treatment for locally advanced GC/GEJC. However, a substantial proportion of patients still experience disease recurrence even after complete resection. Based on the pivotal results of the FLOT4 and ESOPEC trials, perioperative FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) has been established as the standard of care for patients with locally advanced upper gastrointestinal tract adenocarcinoma, including GC/GEJC, in Western countries, whereas surgery followed by adjuvant chemotherapy remains the standard in Asia. The positive findings from the PRODIGY and RESOLVE trials have further supported neoadjuvant and perioperative strategies in Asia, fostering a trend toward global harmonization. Following the first global collaboration in KEYNOTE-585, the randomized phase III MATTERHORN trial represented a major milestone by demonstrating, for the first time, a significant improvement in event-free survival and overall survival with the addition of durvalumab to perioperative FLOT. This provided the first global phase III evidence supporting the integration of immune checkpoint inhibitors with perioperative chemotherapy in GC/GEJC. In this review, we spotlight the paradigm shift in perioperative treatment and address challenges associated with implementing FLOT plus durvalumab in daily practice. We also discuss future therapeutic directions, including molecularly targeted therapies and novel multimodal approaches. The MATTERHORN trial has set the global stage for advancing the management of resectable GC/GEJC, heralding the beginning of a new era.

Drug-induced liver injury with autoimmune-like features is an uncommon yet clinically significant adverse effect of several medications, including statins. Although generally considered safe, atorvastatin has been associated with rare cases of hepatotoxicity that mimic autoimmune hepatitis on histology. We describe a 53-year-old woman with recently diagnosed chronic kidney disease who developed progressive jaundice and right upper quadrant pain shortly after starting atorvastatin. Laboratory evaluation revealed a mixed pattern of liver injury with worsening liver function tests, while serologic studies for viral hepatitis, autoimmune markers, and metabolic diseases were negative. Imaging ruled out biliary or structural abnormalities. Liver biopsy showed features compatible with autoimmune hepatitis. Given the diagnostic challenge, particularly in seronegative presentations, causality and phenotype assessment tools are essential. The updated Roussel Uclaf Causality Assessment Method (RUCAM) is a validated, widely used instrument with good reproducibility in both idiosyncratic DILI and drug-induced autoimmune hepatitis (DIAIH). Similarly, although the Simplified Autoimmune Hepatitis Score was developed for idiopathic autoimmune hepatitis, it can help identify immunemediated features in DILI when interpreted in a clinical context. In this patient, a RUCAM and S-AIH score of 6, together with compatible histology and a clear temporal association with atorvastatin, supported the diagnosis of statin-induced autoimmune-like hepatitis. The patient received corticosteroids, achieving marked clinical and biochemical improvement. This case highlights the need to consider DILI with autoimmune features in patients with unexplained liver injury after recent statin exposure. When autoimmune serologies are negative, liver biopsy and structured tools such as updated RUCAM and S-AIH are crucial to establish the diagnosis and guide timely immunosuppressive therapy. Although rare, statin-induced autoimmune-like hepatitis is serious but potentially reversible.