Translational gastroenterology and hepatology最新文献

Background: The prognosis of gastric cancer (GC) patients with human epidermal growth factor receptor 2 (HER2) positive was poor. To illustrate the underlying effective and distinctive molecular characteristics of programmed cell death protein 1 (PD-1) blockade in the treatment of GC with HER2 positive, we analyzed the survival outcome of PD-1 inhibitors combination regimen as the first-line treatment for GC patients with HER2-positive in China.

Methods: This retrospective real-world study compared the prognoses of first-line systemic treatment of PD-1 inhibitors combined with trastuzumab and chemotherapy (PTC group) and trastuzumab and chemotherapy (TC group) in Chinese patients with HER2-positive GC, and then further to identify the specific and molecular characteristics of PD-1 inhibitors treatment by hierarchical analysis. The patients were matched using propensity score matching (PSM). Overall survival (OS) and progression-free survival (PFS) were used as the primary and secondary endpoints of the study.

Results: A total of 95 patients with HER2-positive GC receiving first-line treatment at Zhongshan Hospital of Fudan University from January 2019 to September 2022 were included. The median OS (24.67 vs. 16.00 months, P=0.01) and median PFS (15.57 vs. 7.57 months, P=0.008) of patients with HER2-positive GC who received PTC regimen were longer than those treated by TC regimen as first-line systemic treatment after PSM analysis. In hierarchical analysis, we discovered that programmed cell death ligand 1 (PD-L1) positive expression in tumor tissues was not a predictor of PD-1 inhibitors in HER2-positive GC. However, PD-L1 was an indicator of better survival outcomes by combined trastuzumab treatment in all GC patients. Furthermore, in the subgroup analysis, we found that the median OS for the PTC group was longer by nearly 8 months than the TC group in patients with HER2 gene copy number [HER2 fluorescence in situ hybridization (FISH) test] more than six, while the median OS for the PTC group was longer by approximately 12 months than the TC group in patients with HER2-positive GC with TP53 mutations.

Conclusions: The results suggested that patients with HER2-positive GC could benefit from PD-1 inhibitors combination with trastuzumab and chemotherapy, especially patients with HER-2 FISH more than six and TP53 mutations.

Background and objective: Acute appendicitis (AA) is a leading cause of emergency abdominal surgery worldwide, with surgical intervention as its mainstay of treatment. As a primarily clinical diagnosis, it is important for physicians to have ample information to diagnose cases accurately. Given the high rates of negative appendectomies, robust diagnostic workups are crucial to minimize unnecessary surgeries and consider adjunct therapy. Various etiologies, including parasitic infections, are associated with AA. In this review, we report that Schistosoma spp., Enterobius vermicularis (E. vermicularis), Taenia spp., and Ascaris lumbricoides (A. lumbricoides) contribute to or mimic AA. As globalization expands, areas once considered "safe zones" for parasites now face higher risks. It is therefore increasingly important for physicians in all countries to recognize the association between parasites and AA and include proper investigations for high-risk patients. Our findings aim to assist physicians on when to consider a parasitic infection and AA, potentially reducing the number of negative appendectomies, as some parasitic infections can be treated with medication alone.

Methods: To our knowledge, this narrative review incorporating three databases (PubMed, Ovid and Embase), is the first to synthesize research on the relationship between parasites and AA. Articles were screened using Covidence, and inclusion criteria required references to Schistosoma spp., E. vermicularis, Taenia spp., and A. lumbricoides. We limited results to English and French manuscripts published between 1949 and 2023. Two independent reviewers performed title and abstract screening, followed by full-text analysis, ultimately selecting 71 studies that met the inclusion criteria.

Key content and findings: Our analysis identifies four parasitic organisms strongly associated with AA-Schistosoma spp., E. vermicularis, Taenia spp., and A. lumbricoides-and highlights countries where these infections are most prevalent. Furthermore, it highlights the need for more research in this area as causal relationships are still yet to be made.

Conclusions: While strong associations exist between parasitic infections and AA, further research is needed to establish a causal relationship.

Self-directed immune-mediated injury to hepatocytes and cholangiocytes results in autoimmune liver disease (AILD). AILD comprises three distinct entities: autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC) and each of these autoimmune conditions has distinct phenotypic, serological, radiologic and laboratory findings. AIH is characterized by injury to the hepatocytes while PBC and PSC occur due to injury to bile ducts. Although, these are considered rare diseases, it is important to note that some patients can present with features characteristic of more than one AILD, and these conditions are described as overlap syndromes (OS). Currently, there is lack of data regarding the epidemiology of OS. Majority of the data regarding the epidemiology of OS comes from single-center and small studies. The clinical features of OS are similar to the underlying AILD. There is also no consensus on how to manage patients with OS and the management is dependent on treating the underlying AILDs. Management of PBC involves use of ursodeoxycholic acid (UDCA), while management of AIH involves the use of steroids and immunosuppressants. In this article, we will review the current literature on various OS and their respective diagnostic criteria. This article will also discuss epidemiology, clinical features, prognosis as well as outcomes among patients with various OS.

Background: Chemotherapy-induced nausea and vomiting (CINV) significantly impact cancer patients' quality of life. Traditional pharmacological treatments often have limited effectiveness and can cause adverse effects. Acupuncture, a key practice in traditional Chinese medicine (TCM), shows promise as a complementary therapy for CINV. The purpose of this study was to explore the effects and underlying mechanisms of acupuncture in treating CINV.

Methods: We employed a multi-faceted approach to comprehensively explore the abnormal performances of CINV model and to elucidate the regulatory effects of acupuncture in treating CINV through the integration of 16S rRNA analysis, serum metabolomics, and network pharmacology.

Results: Acupuncture significantly reduced kaolin consumption, mitigated anorexia, and attenuated body weight loss compared to the model group. Acupuncture was found to modulate the gut microbiota composition, enhancing beneficial taxa and reducing harmful ones. Serum metabolomic analysis revealed significant alterations in metabolic profiles, with acupuncture impacting various metabolites involved in pathways related to fatty acid biosynthesis, urea cycle, and amino acid metabolism. Spearman correlation analysis indicated a significant association between gut microbial taxa and serum metabolites. Furthermore, network pharmacology analysis identified key genes (MAPK1, STAT3, EGFR, AKT1, SRC) and pathways (PI3K/Akt, neuroactive ligand-receptor interaction) associated with the anti-CINV effects of acupuncture. In conclusion, acupuncture holds promise in ameliorating CINV through its multifaceted impact on gut microbiota, serum metabolome, and molecular pathways.

Conclusions: Acupuncture was an adjunctive and important non-drug treatment for CINV, with the protective effects linked to the improvement of gut microbiota disruption and metabolic abnormalities.

Background: Gastroesophageal reflux disease (GERD) presents a complex pathophysiological challenge with intricate interactions among its biological components, yet the mechanisms remain incompletely understood. This study aimed to conduct a quantitative analysis to investigate the concentration and evolution of domain knowledge in GERD research.

Methods: A bibliographic search in PubMed retrieved 18,459 abstracts of experimental studies on GERD, published between 1963 and 2022. Abstracts were scanned automatically for 477 biological components proposed in recent publications, which are represented by a set of (I) genes and molecules (n=180), (II) definition of cytology, histology, and anatomy (n=54), (III) clinical definition (n=243). For each component, semantic synonyms were recovered from catalogues and domain knowledge. The results are visualized as networks indicating the frequency at which different components are referenced together within each abstract.

Results: Over time the GERD network has seen a progression in the increasing of new components and connectivity. The clinical definition appears to be the most abundant, while studies exploring micro-level mechanisms remain notably scarce. Meanwhile, certain pivotal components consistently attract significant attention, forming crucial elements in this multifactorial disease. However, the micro-level analysis reveals a recent plateau in progress, indicating a bottleneck phase currently.

Conclusions: GERD domain knowledge has remained confined within established frameworks over history, highlighting the importance of developing novel integrated research paradigms among endless data to bridge the gap between bench and bedside.

Background: Splenic injury is a rare complication of upper endoscopic procedures described in case reports. These injuries can result in significant morbidity due to the spleen's vascularity and propensity for intraperitoneal bleeds. This review aims to collect data regarding patient characteristics, procedural factors, clinical presentations and treatment courses for analysis.

Methods: A systematic review of case reports on PubMed, Embase, and Web of Science was conducted for splenic injuries following upper endoscopic procedures (as of 14 July 2023). A total of 52 cases from 50 reports were included. All cases were from case reports or series, including conference abstracts, published in English. Cases were excluded if they were: not published in English; dealt with splenic injuries not following upper endoscopic procedures, including colonoscopy; documented a later complication of an upper endoscopic procedure, such as a migrating stent; not case reports or case series, such as review articles. Risk of bias was analyzed with Joanna Briggs Institute critical appraisal tools. Cases were analyzed using descriptive statistics.

Results: The mean age was 56 years, with a median of 55 years, and a range of 21-86 years. Prior abdominal surgeries were identified in 31% of cases (16/52), and chronic pancreatitis in 15% (9/52). Procedural difficulty was reported in 21% (11/52). Most occurred following endoscopic retrograde cholangiopancreatography (ERCP) (71%, 37/52). Common symptoms were abdominal pain (79%, 41/52), hypotension and/or tachycardia (67%, 35/52), and postoperative drops in hemoglobin (58%, 30/52). Mean time to symptom onset was 21 hours, with a median of 4 hours, and a range of 0-144 hours. Most were diagnosed with computerized tomography (69%, 36/52), followed by laparotomy (17%, 9/52). Most were treated surgically (76%, 40/52). Most patients recovered fully (82%, 42/51).

Conclusions: Splenic injury is a rare complication of upper endoscopy that should be considered given the risk for delayed diagnosis and mortality. Most patients presented with abdominal pain and signs of hemorrhagic shock, although many had delayed onset of symptoms. Potential risk factors include prior abdominal surgeries, chronic pancreatitis, and difficult or prolonged procedures. Our review was limited by a low number of cases and inconsistent reporting of variables, which limited our statistical analysis.

Surgical resection is the gold standard for the treatment of intrahepatic cholangiocarcinoma, whenever possible. In selected patients with involvement of the inferior vena cava, the hepatic veins or both, an aggressive surgery requiring vascular resection-reconstruction can be safely performed in experienced hands. Different approaches, including "ex situ", "ante situm" and "in situ" liver resection with or without the use of veno-venous bypass or cold liver perfusion can be used. We present the case of a 70-year-old woman presenting with a 5.5 cm mass located in the segment I compatible with an intrahepatic cholangiocarcinoma. A left hepatectomy extended to the segment I, right paracaval portion along with the resection of the anterior wall of the vena cava and the middle hepatic vein, together with its subsequent reconstruction using the autologous left branch of the portal vein was performed using a veno-venous bypass and hypothermic "in situ" liver perfusion. Major liver resections with vascular reconstructions that require more than 60 minutes of clamping and veno-venous bypass can be accomplished more safely using "in situ" cooling of the liver. The postoperative course was characterized by mild hepatic failure and the patient was discharged on postoperative day 20. In the five years of follow-up, the patient was in good clinical condition and disease-free, but in 2023, she passed away for a disease recurrence.

Background: Hepatitis C virus (HCV) infection causes extrahepatic manifestations involving B-cell dysregulation and autoantibody production. This study aimed to elucidate the positivity rates of four autoantibodies [anti-nuclear antibody (ANA), anti-smooth muscle antibody (ASMA), anti-liver kidney microsomal type 1 (anti-LKM1), and anti-mitochondrial antibody (AMA)] in patients with chronic hepatitis C (CHC) before and after direct-acting antiviral (DAA) therapy compared to those in healthy controls.

Methods: This study enrolled prospectively collected plasma samples from 201 CHC patients [median age, 62 years; 49.8% women; 100% sustained virological response (SVR)] from eight hospitals before and after DAA therapy and 127 healthy individuals. Autoantibodies were detected using indirect immunofluorescence.

Results: The positivity rate of ANA was higher in CHC patients than in healthy controls (32.3% vs. 21.3%, P=0.03) at pretreatment (PreTx) and decreased at SVR (32.3% vs. 23.9%, P=0.009). Female sex and higher globulin levels were related to ANA positivity in the control and CHC patient groups. Thirty-seven (57%) of 65 patients with ANA-positive HCV at PreTx maintained ANA-positivity at SVR. Among the 136 ANA-negative patients at PreTx, 11 (8%) showed newly positive ANA conversion at SVR. Patients with ANA positivity at SVR (n=48) were older and had a higher proportion of advanced liver disease than ANA-negative patients (n=153).

Conclusions: ANA positivity was observed in one-third of CHC patients at PreTx, which was significantly higher than that in healthy controls and decreased after SVR. CHC patients with ANA positivity after SVR were older and had more advanced liver disease than those with ANA negativity, suggesting persistent immune dysregulation after cure.