Search

Background: The Endoscopic Purse-string Suture (EPSS) technique has gained attention for its potential in closing large defects following gastrointestinal procedures. However, its application in fistula closure is not as widely reported. This study aims to evaluate the safety and efficacy of EPSS and naso-jejunal tube feeding in the closure of duodenal cutaneous fistulas and gastric cutaneous fistulas., Methods: This single-center retrospective study, conducted from September 2020 to September 2023 at Tongji University in Shanghai, China, examined the outcomes of EPPS and nasojejunal feeding for patients with gastric and duodenal cutaneous fistulas (n = 10). Demographic data, fistula characteristics, procedure technique and outcomes were evaluated., Results: In this study, the average size of a fistula opening was 7.9 ± 4.6 mm. The operations took an average of 25.8 ± 5.6 min. Patients typically needed naso-jejunal tube feeding for a median of 14.0 days, with an interquartile range (IQR) of 7.7-19.0 days. The median duration of hospital stay post-operation was 16.5 days, with an IQR of 7.0-25.0 days. Nine patients were successful in their initial fistula closure using the EPSS technique. The other patient underwent a second EPSS and, ultimately, all patients experienced complete healing and fully recovered. There were no major adverse events reported., Conclusions: EPSS and naso-jejunal tube feeding are a safe and effective treatment option for duodenal and gastric cutaneous fistulas. Larger, prospective studies are needed to validate these findings and establish the long-term safety and efficacy of this approach., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Intestinal inflammation modifies host physiology to promote the occurrence of colorectal cancer (CRC), as seen in colitis-associated CRC. Gut microbiota is crucial in cancer progression, primarily by inducing intestinal chronic inflammatory microenvironment, leading to DNA damage, chromosomal mutation, and alterations in specific metabolite production. Therefore, there is an increasing interest in microbiota-based prevention and treatment strategies, such as probiotics, prebiotics, microbiota-derived metabolites, and fecal microbiota transplantation. This review aims to provide valuable insights into the potential correlations between gut microbiota and colitis-associated CRC, as well as the promising microbiota-based strategies for colitis-associated CRC.

Re-expression of an embryonic morphogen, Nodal, has been seen in several types of malignant tumours. By far, studies about Nodal's role in colorectal cancer (CRC) remain limited. Ferroptosis is essential for CRC progression, which is caused by cellular redox imbalance and characterized by lipid peroxidation. Herein, we observed that Nodal enhanced CRC cell's proliferative rate, motility, invasiveness, and epithelial-mesenchymal transition (EMT) in vivo and in vitro. Notably, Nodal overexpression induced monounsaturated fatty acids synthesis and increased the lipid unsaturation level. Nodal knockdown resulted in increased CRC cell lipid peroxidation. Stearoyl-coenzyme A desaturase 1 (SCD1) inhibition at least partially abolished the resistance of Nodal-overexpressing cells to RSL3-induced ferroptosis. Mechanistically, SCD1 was transcriptionally up-regulated by Smad2/3 pathway activation in response to Nodal overexpression. Significant Nodal and SCD1 up-regulation were observed in CRC tissues and were associated with CRC metastasis and poor clinical outcomes. Furthermore, bovine serum albumin nanoparticles/si-Nodal nanocomplexes targeting Nodal had anti-tumour effects on CRC progression and metastasis. This research elucidated the role of Nodal in CRC development and revealed a potential gene-based therapeutic strategy targeting Nodal for improving CRC treatment., (© 2023. The Author(s).)

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide because of metastasis. An increasing number of studies have reported that cancer-associated fibroblasts (CAFs) have emerged as the largest component of the stroma and play a critical role in tumor-promoting processes. However, the effects of CAFs on cancer progression and the sensitivity of hepatoma cells to sorafenib are not well characterized. Here, we identified the proteome of CAF-derived exosomes, and unveiled that exosomal Gremlin-1 derived from CAFs contributes to epithelial-mesenchymal transition (EMT) of hepatoma cells and the decrease of the sorafenib sensitivity through regulating Wnt/β-catenin and BMP signaling pathways. Compared to control subjects, the level of plasma exosomal Gremlin-1 was significantly increased in HCC patients. Further studies indicated that plasma exosomal Gremlin-1 may predict sorafenib response in HCC patients. Collectively, our findings uncover CAFs-derived Gremlin-1-rich exosomes promote EMT and decrease the sensitivity of hepatoma cells to sorafenib by Wnt/β-catenin and BMP signaling., (© 2022 Wiley Periodicals LLC.)

Background: Crohn's disease (CD) is a chronic nonspecific inflammatory bowel disease (IBD) with an increasing incidence worldwide. The etiology of CD is still obscure, but microbial dysbiosis has been recognized as an essential factor contributing to CD. However, few studies have revealed the microbiome's signatures and reciprocal correlations between multiple sites in patients with CD over different disease stages. This study investigated the specific microbial architectures of the oral cavity, sputum, and ileum in patients with CD in the active and remission stages., Methods: Microbial samples from the oral cavity, sputum, and ileum were collected from patients with CD in the active and remission stages and healthy controls. The microbial composition was assessed by 16S ribosomal RNA (rRNA) gene sequencing. In addition, bioinformatics methods were used to demonstrate the microbial signatures, functional changes, and correlations between microbiota and clinical data in CD., Results: Compared with healthy controls, a distinct microbiota dysbiosis in the oral cavity, sputum, and ileum of patients with CD was identified, characterized by alterations in microbiota biodiversity and composition. The oral cavity and sputum microbiota showed significantly lower microbial diversity in patients with CD than in healthy controls. In terms of microbiota composition, the microbiota changes in the oral cavity of patients with CD were similar to those in the sputum, while they were different from those in the ileum. In the oral cavity and sputum of patients with CD, a lower relative abundance of Firmicutes and Actinobacteria was observed compared to healthy controls, which was most prominent in the active stage. In contrast, an increased relative abundance of Fusobacteria , Porphyromonas , and Haemophilus was observed in patients with CD. The predicted metabolic pathways involved in the oral cavity, sputum, and ileum were similar, predominantly involving metabolism, environmental information processing, and genetic information processing., Conclusion: The results revealed the alterations of microbiota architecture in the oral cavity, sputum, and ileum of patients with CD, which varied across disease stages. Studying microbiota dysbiosis may bring new insights into the etiology of CD and lead to novel treatments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xia, Gao, Wu, Sun, Wan, Wu, Fichna, Yin and Chen.)

Accumulating evidence indicates that gut microbiota dysbiosis contributes to colorectal cancer and adenoma. However, a few studies revealed the altered gut mycobiota architecture in colorectal cancer. The present study characterized the gut mycobiota profiles in adenoma and colorectal cancer patients by metagenomic sequencing. Malassezia restricta increased, while Leucoagaricus_sp_SymCcos and fungal_sp_ARF18 significantly decreased in adenoma. Phanerochaete_chrysosporium , Lachancea_waltii , and Aspergillus_rambellii were the top 3 fungi that were significantly enriched in colorectal cancer, while Candida_versatilis , Pseudocercospora_pini_densiflorae , and Candida_sp_JCM_15000 were dominant in the healthy controls. Thirteen fungi, ranked as critical biomarkers in diagnosing colorectal cancer, showed positive associations among all samples. Lachancea_waltii and Phanerochaete_chrysosporium showed the most significant association within CRC. The values of area under the receiver-operating characteristics curve (AUROC) of selected 13 mycobiota were 0.926 in the training model and 0.757 in the 10-fold validation model. Our study provided a reliable investigation of the alterations of gut mycobiota in the development of colorectal cancer and established a convincing diagnostic model for colorectal cancer, which might improve the treatment strategy for colorectal cancer in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gao, Xia, Wu, Zhong, Sun, Zhu, Huang, Wu, Yin, Yang, Chen and Qin.)

Background: Treatment of rectovaginal fistulas (RVFs) is extremely difficult. No standard surgical procedure is accepted worldwide. The aim of this article was to evaluate a minimally invasive procedure for the repair of mid-low rectovaginal fistula., Methods: This is a retrospective review of 17 patients who underwent minimally invasive surgery for the repair of mid-low rectovaginal fistulas (located in the lower or middle one-third of the vaginal wall) at our center between August 2016 and October 2018. The anal approach was adopted for 12 patients: 6 patients were treated directly by rectal mucosal advancement flap (RMAF) with transanal endoscopic surgery (TES), while the other 6 patients underwent initial TES exploration followed by RMAF procedure under direct vision. The vaginal approach was adopted for 5 patients: 3 patients were treated under TES directly and the other 2 were treated under direct vision after initial TES exploration. A total of 9 (52.94%) patients received diverting ileostomy-5 anal approach patients and 4 vaginal approach patients., Results: Median age of the patients was 46 years (range 10-76 years), and median BMI was 21.9 (range 17.9-28.1). Median operative time was 75 min (range 60-120 min), and median duration of postoperative hospital stay was 8 days (range 6-15 days). Recurrence was seen in 3/12 anal approach patients vs. 0/5 vaginal approach patients. Both the median preoperative and the median postoperative Wexner score were 0 (range 0-2). The median follow-up time was 8 months (range 2-24). No severe complications occurred in any patient., Conclusion: The TES procedure for the treatment of mid-low rectovaginal fistulas avoids any incision of the abdomen and perineal area and appears to be a safe and feasible procedure. This minimally invasive technique is still evolving and is likely to gain wide acceptance in the near future.

Cancer-associated fibroblasts (CAFs) play crucial roles in enhancing cell survival, proliferation, invasion, and metastasis. We previously showed that hepatocellular carcinoma-derived CAFs (H-CAFs) promoted proliferation of hepatocellular carcinoma (HCC) cells. This study aimed to further explore the role of CAFs in HCC epithelial-mesenchymal transition (EMT) and the underlying mechanism. High CAF density was significantly associated with liver cirrhosis, inferior clinicopathologic characteristics, elevated EMT-associated markers, and poorer survival in human HCC. Within HCC cells, EMT was induced after co-culture with H-CAFs. Secretomic analysis showed that IL-6 and HGF were the key EMT-stimulating cytokines secreted by H-CAFs. Proteomic analysis revealed that TG2 was significantly upregulated in HCC cells with EMT phenotypes. Overexpression of TG2 promoted EMT of HCC cells, and knockdown of TG2 remarkably attenuated the H-CAF-induced EMT. Furthermore, during EMT, TG2 expression was enhanced after HCC cells were stimulated by IL-6, but not HGF. Inhibition of the IL-6/STAT3 signaling decreased TG2 expression. The principal TG2 transcription control element and a potential STAT3 binding site were identified using promoter analysis. Hence, H-CAFs facilitates HCC cells EMT mediated by IL-6, which in turn activates IL-6/IL6R/STAT3 axis to promote TG2 expression., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Few studies have assessed the short- and long-term outcomes of laparoscopically assisted natural orifice specimen extraction (NOSE) in patients with sigmoid colon and rectal tumors. We investigated the short- and long-term outcomes of patients undergoing laparoscopic-assisted NOSE for tumors of the sigmoid colon and rectum. Methods: Ninety-eight patients with sigmoid colon and rectal tumors undergoing laparoscopic-assisted NOSE were included. The tumor was classified according to its distance from the anal verge: Group 1 (15-30 cm), Group 2 (5-15 cm), and Group 3 (≤5 cm). In Group 1 patients, a laparoscopic surgical specimen collection bag was used as a special transrectal device. In Group 2 patients, transanal endoscopic microsurgery device and specimen collection bag were used. In Group 3 patients, a Lone-Star retractor was used. The demographic characteristics and intra- and postoperative outcomes were measured. Results: In Group 1, 1 patient had respiratory disease and 1 had enterocolitis as short-term postoperative complications. One patient showed intestinal obstruction as a long-term postoperative complication. In Group 2, 2 patients had an ileus, 1 had an anastomotic leak, 2 had urinary retention, and 1 had respiratory disease as short-term complications. Only one patient had a long-term complication: anastomotic stenosis. In Group 3, short-term complications were present in 3 patients: 1 had hemorrhage, 1 had urinary retention, and 1 had respiratory disease. Long-term complications included one case of anastomotic stenosis and one of intestinal obstruction. Conclusions: NOSE is safe and cosmetically and theoretically superior to conventional laparoscopy when different devices are used according to the tumor's location.

Background: Sex hormone-binding globulin (SHBG), a glycoprotein synthesized by hepatocytes, has been linked to insulin resistance and hepatic lipid metabolism and is suggested to be associated with nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate the association of SHBG with NAFLD in Chinese adults., Methods: We conducted a community-based, cross-sectional study in China involving 2912 participants aged 40-75 years old. All participants underwent detection for hepatic fat infiltration by ultrasound in addition to providing complete medical history and undergoing physical and blood biochemical examinations. The association of serum SHBG with the presence of NAFLD was reported by adjusted odds ratio after applying logistic regression models. To further explore the relationship between SHBG and NAFLD, mRNA expression of SHBG and hepatocyte nuclear factor 4-α (HNF4α), as well as intrahepatic triglycerides, were determined from the liver tissues of 32 subjects with different degrees of steatosis., Results: Serum SHBG levels in patients with NAFLD (median, 43.8 nmol/L; interquartile range, 33.4-56.8 nmol/L) were significantly lower than those in non-NAFLD subjects (median, 63.4 nmol/L; interquartile range, 47.6-83.1 nmol/L). Serum SHBG levels were inversely correlated with WHR, trunk fat percentage, glucose, HOMA-IR, TG, UA and DHEAS, and were positively correlated with HDL-C levels (all p  <  0.001). Logistic regression analysis indicated that serum SHBG levels were negatively associated with the presence of NAFLD in all subjects, as well as the subgroups stratified by sex, BMI and HOMA-IR (all p  <  0.05). In human liver tissues, SHBG and HNF4α mRNA expression decreased along with the elevated grade of hepatic steatosis. Both SHBG and HNF4α mRNA expression levels were negatively correlated with intrahepatic triglycerides., Conclusions: These results demonstrate that SHBG levels were negatively associated with the presence of NAFLD in middle-aged and elderly Chinese adults., Competing Interests: Written informed consent was provided by all participants, and the study was approved by the Ethics Committee of the School of Public Health at Sun Yat-sen University (Approval Number ZDGWYL2009–3, Registration Number NCT03179657, www.ClinicalTrials.gov), which meets the ethical standards established in the Declaration of Helsinki.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Hepatic ischemia reperfusion injury (IRI) is an inevitable clinical problem for liver surgeons. Because microRNAs (miRNAs) participate in various hepatic pathophysiological processes, this study aimed to explore the role and potential mechanism of miR-124 in hepatic IRI., Methods: A liver IRI model was established in rats. The differential expression of miRNAs was detected using microarrays, and the expression of miR-124 was measured by qRT-PCR. A hydrogen peroxide (H2O2)-induced oxidative stress apoptosis model was also established. Cell apoptosis was detected by flow cytometry, and viability was detected by CCK8. The expression of Rab38 was detected by Western blotting and qRT-PCR, and a luciferase reporter assay was used to verify the expression of the miR-124 target gene., Results: The miRNA spectrum changes dramatically after hepatic IRI in rats, and miR-124 is significantly down-regulated after liver IRI. MiR-124 decreases the H2O2-induced apoptosis of human hepatic L02 cells by up-regulating the activation of the AKT pathway. Rab38 is a target gene of miR-124 and is involved in H2O2-induced apoptosis. Interference with the expression of the Rab38 gene can protect hepatic L02 from H2O2-induced apoptosis by increasing the phosphorylation of AKT. These protective effects of miR-124 are attenuated by over-expression of Rab38., Conclusions: Many miRNAs are involved in hepatic IRI in rats, and miR-124 is significantly decreased in this model. MiR-124 significantly decreases the H2O2-induced apoptosis of human hepatic L02 cells by targeting the Rab38 gene and activating the AKT pathway., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: To explore the expression of Yes-associated protein (YAP) in hepatocellular carcinoma (HCC) patients, and assess its prognostic value to recurrence of HCC after liver transplantation (LT)., Methods: Collected data of 105 consecutive patients undergoing LT for HCC were analyzed retrospectively. The immunohistochemistry was used to detect the expression of YAP, Mst1, Lats1/2, pYAP, pLats1/2 and pMst1/2 in tumor tissues. Contingency table and χ(2)-test were used to investigate the correlation between expression of YAP, Mst1, Lats1/2 and clinical characteristics. Univariate survival analysis and Multivariate Cox regression analysis were also performed to analyze the correlation of clinical and pathological factors with tumor recurrence after LT. The Kaplan-Meier method and log-rank test were used to analyze HCC-specific disease-free survival (DFS) rate., Results: Forty patients fulfilled Milan criteria with 1-, 2-, 3- and 5-years DFS of 86.7, 84.6, 84, 84%, respectively. The positive rates of YAP, Lats1/2, Mst1 in HCC were 51.4, 45.7, 64.8%, respectively. YAP expression in HCC tumors was significantly associated with tumor size (p = 0.041), venous infiltration (p = 0.002), AJCC tumor stage (p = 0.027). Lats1/2 expression was significantly associated with tumor size (p = 0.001) and AJCC tumor stage (p = 0.019). Mst1 expression was also significantly associated with tumor size (p = 0.042). HCC-specific DFS was significantly longer for patients with YAP negative expression compared with patients with YAP positive expression (1-, 2-, 3- and 5-years DFS of 71.7, 65.3, 65.3, 65.3 vs. 42.5, 36.6, 32.5, 30.4%, respectively, log-rank = 12.89, p < 0.001). Multivariate Cox regression analysis indicated that YAP expression (HR = 2.011, p = 0.020) in HCC was an independent prognostic factor for HCC-specific DFS after liver transplantation., Conclusions: YAP is an independent prognostic marker for tumor recurrence for HCC patients after liver transplantation., (© 2015 S. Karger AG, Basel.)