Clinical studies demonstrated a correlation between sleep dysfunction and intestinal diseases. However, the detailed interactions and underlying mechanisms linking sleep disruption to intestinal microenvironment remain poorly understood. We employed the Curling Prevention by Water (CPW) paradigm to establish a mouse model of sleep deprivation (SD) for durations ranging from 0 to 96 h. The dynamic changes in the intestinal microenvironment were systematically profiled using multi-omics approaches, including metagenomic sequencing, untargeted metabolomics and RNA sequencing. The causal role of microbial dysbiosis and the underlying mechanisms were further investigated using germ-free mice, fecal microbiota transplantation (FMT), flow cytometry, and targeted intervention. The intestinal microenvironment was highly sensitive to SD. Distinct microbial communities and metabolite profiles were observed among brief SD (< 24 h of SD), prolonged SD (24–96 h of SD) and control. Brief SD triggered a self-regulatory response of the gut microbiota, characterized by an increase in certain beneficial bacteria (e.g., Parabacteroides goldsteinii). In contrast, prolonged SD shaped a pro-inflammatory microbial structure, characterized by reduced Akkermansia muciniphila and enriched Pseudomonadota. Multi-omics analysis revealed that SD significantly inhibited microbial bile acid metabolism, particularly taurodeoxycholic acid (TDCA), and impaired intestinal barrier function while suppressing the intestinal immune response to bacteria antigens. Mechanistically, SD exacerbated intestinal barrier damage by inhibiting the TDCA/group 3 innate lymphoid cells (ILC3)/IL-22 axis. Supplementation with TDCA effectively restored ILC3 function, IL-22 production, and barrier integrity in SD mice. Furthermore, FMT from patients with sleep dysfunction significantly disturbed intestinal microenvironment and increased serum cortisol by regulating gut microbiota and inhibiting TDCA/ILC3/IL-22 axis. This study dynamically delineates how SD disrupts intestinal homeostasis by reshaping the gut microbiota and suppressing the TDCA/ILC3/IL-22 axis. These findings provide novel mechanistic insights and identify potential therapeutic targets for sleep dysfunction-associated intestinal complications.
BACKGROUND Perineal small bowel fistula (PSF) is a highly debilitating complication of radical pelvic malignancy resections. It is typically driven by empty pelvis syndrome (EPS) and chronic adhesive disease. Current therapeutic guidelines lack standardization. AIM To evaluate an etiology-driven surgical algorithm, where procedures are chosen based on the underlying mechanism, aiming to improve closure rates. METHODS Retrospective cohort analysis was performed on 28 consecutive patients who underwent definitive repair for complex PSF. Patients were stratified into two surgical groups based on etiology: Group 1 (n = 15) underwent modified pelvic floor reconstruction for structural defects or EPS; group 2 (n = 13) underwent internal intestinal plication for extensive adhesions or tumor recurrence. Overall survival was calculated from the date of definitive surgery to the last follow-up or death. RESULTS The study cohort (mean age 56.6 years) included patients with rectal (35.7%), gynecological (35.7%), and various other pelvic malignancies. There were no significant baseline demographic differences between the groups. A significant correlation was observed between fistula etiology and surgical strategy (P = 0.02). While reconstruction was the exclusive surgical approach for patients with EPS (100%), plication was predominantly utilized for cases of tumor recurrence (66.7%). The overall fistula closure rate was 89.3% (25/28), showing no significant difference between group 1 (86.7%) and group 2 (92.3%; P = 1.0). However, group 2 experienced a significantly longer mean time to postoperative flatus (6.8 days vs 4.2 days; P = 0.002). The median follow-up time for the entire cohort was 34.5 months (range: 9.0-107.0 months). Overall survival was comparable across the two surgical groups (32.0 months vs 37.0 months; P = 0.66). CONCLUSION Managing complex PSFs requires a tailored approach. Employing an etiology-driven strategy, specifically pelvic floor reconstruction for structural voids (EPS) and internal intestinal plication for “frozen” adhesive conditions, achieves > 89% closure rates with acceptable morbidity.
Crohn’s disease (CD) often necessitates surgical intervention, with temporary stoma creation after intestinal resection (IR) being a crucial decision. This study aimed to construct novel models based on machine learning (ML) to predict temporary stoma formation after IR for CD. Patient data who underwent IR for CD at our center between July 2017 and March 2023 were collected for inclusion in this retrospective study. Eligible CD patients were randomly divided into training and validation cohorts. Feature selection was executed using the least absolute shrinkage and selection operator. We employed three ML algorithms including traditional logistic regression, novel random forest and XG-Boost to create prediction models. The area under the curve (AUC), accuracy, sensitivity, specificity, precision, recall, and F1 score were used to evaluate these models. SHapley Additive exPlanation (SHAP) approach was used to assess feature importance. A total of 252 patients with CD were included in the study, 150 of whom underwent temporary stoma creation after IR. Eight independent predictors emerged as the most valuable features. An AUC between 0.886 and 0.998 was noted among the three ML algorithms. The random forest (RF) algorithms demonstrated the most optimal performance (0.998 in the training cohort and 0.780 in the validation cohort). By employing the SHAP method, we identified the variables that contributed to the model and their correlation with temporary stoma formation after IR for CD. The proposed RF model showed a good predictive ability for identifying patients at high risk for temporary stoma formation after IR for CD, which can assist in surgical decision-making in CD management, provide personalized guidance for temporary stoma formation, and improve patient outcomes.
Crohn's disease (CD), a type of inflammatory bowel disease (IBD), is a chronic disorder involving any part of the gastrointestinal tract. Ileocecal resection may serve as a more effective treatment option for early CD. However, the potential relationship and mechanisms between the ileocecum and remission induction of CD are still elusive. In this study, we conducted 16S rRNA sequencing and liquid chromatography-tandem mass spectrometry (LC-MS/MS) on 68 terminal ileal mucosa and mesentery samples from 34 patients with CD. The results showed an improvement in the microbial health of the ileal mucosa and mesentery in patients with CD after ileocecal resection. In addition, specific spatial alterations in microbiota and metabolites were observed before and after surgery. Furthermore, differentially expressed metabolites in the ileal mucosa and mesentery were subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The findings of this study support the therapeutic value of ileocecal resection in CD from a multi-omics perspective and may guide the clinical translation of microbiome-based strategies for precise treatment of CD.
[Objectives] To investigate the clinical effectiveness of laparoscopic surgical techniques in the treatment of patients with radiation-induced intestinal fistula. [Methods] The clinical data of 14 patients with radiation-induced intestinal fistula who underwent laparoscopic surgical techniques at the Center for Difficult and Complicated Abdominal Surgery, Tenth People’s Hospital of Tongji University from January 2020 to December 2024 were retrospectively analyzed. The basic information about the patients, surgical-related conditions, and postoperative follow-up conditions (follow-up through telephone or outpatient visits) were recorded. [Results] Among the 14 patients, the primary tumor diagnoses included 8 cases of cervical cancer, 2 cases of prostate cancer, and 4 cases of rectal cancer; the intestinal fistula diagnoses included 7 cases of recto-vaginal fistula, 2 cases of vesico-rectal fistula, 1 case of vesico-sigmoid fistula, 1 case of recto-vaginal fistula combined with vesico-rectal fistula, 1 case of rectal fistula, 1 case of small intestine-vaginal fistula, and 1 case of small intestine-presacral fistula; the number of previous surgeries ranged from 2 to 4. In this radiation-induced intestinal fistula surgery: all patients underwent laparoscopic exploration, among whom 6 patients underwent totally laparoscopic surgery, and 8 patients were converted to open surgery after laparoscopic exploration and partial adhesion lysis to complete other surgical procedures; the operative time ranged from 2 to 7 hours; the hospital stay ranged from 5 to 34 days. One patient underwent emergency surgery due to severe intra-abdominal infection and died of disseminated intravascular coagulation on the 10th day after surgery; one patient had an anastomotic leakage 1 month after surgery, underwent ileostomy, and had the ileostomy reversed 6 months later; the remaining 12 patients had good postoperative recovery and showed good food intake and defecation during the 3-month postoperative follow-up. [Conclusion] Based on emphasizing the perioperative management of patients with radiation-induced intestinal fistula, optimizing the methods of preoperative localization and Trocar layout strategy, and with the implementation by an experienced surgical team, the overall safety and feasibility of laparoscopic surgical techniques for radiation-induced intestinal fistula are good.
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. 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. 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. 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.
BACKGROUND Due to the complexity and numerous comorbidities associated with Crohn’s disease (CD), the incidence of postoperative complications is high, significantly impacting the recovery and prognosis of patients. Consequently, additional studies are required to precisely predict short-term major complications following intestinal resection (IR), aiding surgical decision-making and optimizing patient care. AIM To construct novel models based on machine learning (ML) to predict short-term major postoperative complications in patients with CD following IR. METHODS A retrospective analysis was performed on clinical data derived from a patient cohort that underwent IR for CD from January 2017 to December 2022. The study participants were randomly allocated to either a training cohort or a validation cohort. The logistic regression and random forest (RF) were applied to construct models in the training cohort, with model discrimination evaluated using the area under the curves (AUC). The validation cohort assessed the performance of the constructed models. RESULTS Out of the 259 patients encompassed in the study, 5.0% encountered major postoperative complications (Clavien-Dindo ≥ III) within 30 d following IR for CD. The AUC for the logistic model was 0.916, significantly lower than the AUC of 0.965 for the RF model. The logistic model incorporated a preoperative CD activity index (CDAI) of ≥ 220, a diminished preoperative serum albumin level, conversion to laparotomy surgery, and an extended operation time. A nomogram for the logistic model was plotted. Except for the surgical approach, the other three variables ranked among the top four important variables in the novel ML model. CONCLUSION Both the nomogram and RF exhibited good performance in predicting short-term major postoperative complications in patients with CD, with the RF model showing more superiority. A preoperative CDAI of ≥ 220, a diminished preoperative serum albumin level, and an extended operation time might be the most crucial variables. The findings of this study can assist clinicians in identifying patients at a higher risk for complications and offering personalized perioperative management to enhance patient outcomes.
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.
Locally advanced colon cancer includes stage Ⅲ and high-risk stage Ⅱ colon cancer (with tumor invasion depth of T4 stage). Both national and international guidelines recommend surgery as the primary treatment, followed by adjuvant chemotherapy. However, even with standardized treatment executed, up to 30% of patients still experience recurrence and metastasis. Therefore, strategies to improve the prognosis of patients with advanced colon cancer remains a focal point of research. Most completed and ongoing clinical trials haved focused on neoadjuvant therapy. Unlike rectal cancer, there is not an laternative to sugery when treating locally advanced colon cancer, even after comprehensive neoadjuvant therapy. This article provides a literature review on the current status of comprehensive treatment of locally advanced colon cancer.
本研究回顾性分析1例经自然腔道取标本全腹腔镜胰十二指肠切除术联合全结肠切除术治疗Turcot综合征患者的临床资料,该患者为39岁女性,因上腹痛伴排便习惯改变2个月余入院,既往有脑部恶性肿瘤手术史,入院完善检查发现十二指肠肿瘤、家族性息肉病,结合患者对微创治疗及远期疗效的综合要求行经自然腔道取标本全腹腔镜胰十二指肠切除术联合全结肠切除术。患者术后随访4年余,生存良好,无明显肿瘤复发迹象,本研究提示行经自然腔道取标本全腹腔镜胰十二指肠切除术联合全结肠切除术治疗此类患者安全可行,远期疗效较好。
盆腔局部晚期恶性肿瘤包括盆腔局部进展期或复发的结直肠癌、盆腔局部进展期或区域复发的妇科恶性肿瘤(宫颈癌、子宫内膜癌、卵巢癌)和盆腔局部复发的泌尿系统恶性肿瘤(前列腺癌、膀胱癌).对于这类恶性肿瘤,全盆腔切除是唯一可能的治愈方法,而其安全性和有效性则有赖于几大关键技术的进步,包括泌尿系统风险及功能保存、微创手术、血管切除与重建、邻近骨切除等技术的进步.本文就全盆腔切除治疗盆腔恶性肿瘤的关键技术进步情况进行了文献述评.
患者,男性,66岁,2020年10月因多灶食管癌于外院行"胸腹腔镜食管癌根治术+纵隔淋巴结清扫+部分胃切除代食道+空肠营养性造口术".术后病理提示:(食管上段)鳞状细胞癌,标本上切缘(-),标本下切缘(-);组织分化程度:中-低分化;浸润深度:浸润至黏膜下层;脉管内癌栓(+),神经侵犯(-),另送上切缘(+).(右侧喉返神经旁淋巴结)查见淋巴结(1/3)见癌转移,余送检淋巴结均无癌转移.术后并发食管吻合口瘘,在胃镜下行瘘口夹闭术失败.但在胃镜检查的同时发现声门下有新生物,病理活检提示:(声门下)鳞状细胞癌.
Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract with an increasing incidence worldwide. Comprehensive therapy for CD focuses on symptom control and healing the intestinal mucosa to improve the quality of life and prevent complications. Surgical intervention plays a vital role in comprehensive therapy. However, deciding the optimal timing for surgical intervention has long been a focus of controversy. This review provides insights into the timing of surgery for CD and guides clinicians in daily treatment.
患者女,41岁。2021年6月出现便血,呈鲜红色。同年8月肠镜检查提示:距肛门口6 cm以下至肛门见1个隆起凹陷性病变,黏膜坏死有渗出,触之易出血,占肠腔周径约4/5。肛门口可见隆起肿物,质地硬。同时患者诉阴道内有排气、排便,色黄。直肠指检:左侧卧位肛门口见肿物突出,直肠下端5 cm至肛门3~6点方向可触及质硬肿块,不可推动,指套退出有染血。下腹部增强MRI检查:直肠、肛管占位,考虑恶性肿瘤性病变,侵及外膜及邻近盆底肌,直肠周围间隙、盆腔及两侧腹股沟区多发淋巴结部分肿大(图1A)。经肛门碘水造影:直肠肠腔部分狭窄,考虑直肠阴道瘘存在。血常规检查:红细胞3.18×10 12/L,血红蛋白54 g/L。诊断为直肠肛管占位、直肠阴道瘘、重度贫血。予以输血、肠外营养等对症治疗后,择期行腹腔镜下女性后盆腔廓清术(腹腔镜下腹会阴直肠切除+经腹子宫扩大切除+双侧输卵管卵巢切除+阴道部分切除+阴道会阴成形术)。病理检查提示:肛管鳞癌,中分化,癌浸润肠壁全层至肠壁外纤维结缔组织,局灶累及阴道壁,部分至黏膜面伴溃疡形成。肿瘤大小:7.0 cm×4.0 cm×3.5 cm,未见明确神经、脉管侵犯(图1B、1C)。肠周淋巴结未见癌转移(0/17)。(253组淋巴结)未见癌转移(0/8)。免疫组化检查:肿瘤细胞ck-p(+),ck7(+),ck20(-),villin(+),p63(+),p40(+),ck5/6(+),p16(+),p53(++),cea(+),cd34(血管+),pd-1(-),pd-11(tps:3%;cps:5),ki-67(70%+)。术后随访半年,患者会阴部伤口已愈合,造口皮肤红润,通畅,未发现并发症。术后序贯化学治疗,未见肿瘤复发征象。
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.
通过外科手术将肿瘤完全切除,是肿瘤根治的重要手段.已有文献表面对这部分患者进行辅助治疗有助于提高患者无病生存率以及总体生存率.术后辅助治疗的临床决策又取决于肿瘤分期.本文将围绕常见的消化道肿瘤及妇科肿瘤等肿瘤的术后辅助治疗进行综述,尝试初步解答肿瘤术后患者辅助治疗的临床决策问题.
BACKGROUND:Long non-coding RNA (lncRNA) H19 has been reported to involve in many kinds of human cancers and functions as an oncogene. Our previous study found that H19 was over-expressed in gallbladder cancer (GBC) and was shown to promote tumor development in GBC. However, the competing endogenous RNA (ceRNA) regulatory network involving H19 in GBC progression has not been fully elucidated. We aim to detect the role of H19 as a ceRNA in GBC.METHODS AND RESULTS:In this study, the expression of H19 and miR-342-3p were analyzed in 35 GBC tissues and matched normal tissues by using quantitative polymerase chain reaction (qRT-PCR). We demonstrated H19 was overexpressed and negatively correlated with miR-342-3p in GBC. By dual-luciferase reporter assays, RNA-binding protein immunoprecipitation (RIP) and RNA pull-down assays, we verified that H19 was identified as a direct target of miR-342-3p. QRT-PCR and Western-blotting assays demonstrated that H19 silencing down-regulated, whereas over-expression enhanced the expression of miR-342-3p targeting FOXM1 through competitively 'sponging' miR-342-3p. Furthermore, transwell invasion assays and cell cycle assays indicated that H19 knockdown inhibited both cells invasion and proliferation, but this effects was attenuated by co-transfection of siRNA-H19 and miR-342-3p inhibitor in GBC cells. In vivo, tumor volumes were decreased significantly in H19 silenced group compared to the control group, but was attenuated by co-transfection of shRNA-H19 and miR-342-3p inhibitor, which were stablely constructed through lenti-virus vector.CONCLUSION:Our results suggest a potential ceRNA regulatory network involving H19 regulates FOXM1 expression by competitively binding endogenous miR-342-3p in GBC. This mechanism may contribute to a better understanding of GBC pathogenesis and provides potential therapeutic strategy for GBC.
患者男,36岁,因"反复腹痛12年,腹痛、腹胀伴呕吐4 d"就诊。既往有克罗恩病病史,长期内科药物治疗。入院后体格检查示中下腹压痛,可触及下腹部包块。入院后完善相关检查,诊断为大肠克罗恩病(活动期)、小肠梗阻、乙状结肠狭窄、重度营养不良。予留置经鼻肠梗阻导管,排除手术禁忌证后择期行腹腔镜结肠次全切除+回盲部切除+肠粘连松解+小肠排列术+回肠造口术。术后患者恢复良好,出院后随访患者一般情况良好,未发生严重并发症。克罗恩病合并腹内疝继发急性肠梗阻临床罕见,本文通过介绍此例患者的发病、诊断和治疗情况,为此类患者的治疗提供参考,提高临床医师对克罗恩病合并腹内疝的认识。
本研究对28例经组织活检或手术病理证实的胃肠道淋巴瘤实验室检查、影像学检查、内镜检查及临床资料进行回顾性分析。结果表明28例原发性胃肠淋巴瘤患者中男性占50%,包括12例胃淋巴瘤,7例小肠淋巴瘤,7例结肠淋巴瘤,2例胃结肠多发淋巴瘤。有7例患者出现血清CA125升高。手术21例,其中因肠梗阻、出血、穿孔急诊手术10例,术前误诊为胃肠癌、炎症性肠病、胃肠道间质瘤共计11例。胃肠道淋巴瘤容易误诊,外科医师要重视淋巴瘤的综合诊断,避免对多部位胃肠淋巴瘤漏诊,遵循病理金标准,不盲目手术,同时要关注存在碰撞瘤的可能。