Predicting short-term major postoperative complications in intestinal resection for Crohn's disease: A machine learning-based study.

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.

Timing of individualized surgical intervention in Crohn's disease.

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.

Laparoscopic vs open surgery in ileostomy reversal in Crohn's disease: A retrospective study.

BACKGROUND: Although minimally invasive surgery is becoming more commonly applied for ileostomy reversal (IR), there have been relatively few studies of IR for patients with Crohn's disease (CD). It is therefore important to evaluate the potential benefits and risks of laparoscopy for patients with CD. AIM: To compare the safety, feasibility, and short-term and long-term outcomes of laparoscopic IR (LIR) vs open IR (OIR) for the treatment of CD. METHODS: The baseline characteristics, operative data, and short-term (30-d) and long-term outcomes of patients with CD who underwent LIR and OIR at our institution between January 2017 and January 2020 were retrieved from an electronic database and retrospectively reviewed. RESULTS: Of the 60 patients enrolled in this study, LIR was performed for 48 and OIR for 12. There were no statistically significant differences in baseline characteristics, operation time, intraoperative blood loss, days to flatus and soft diet, postoperative complications, hospitalization time, readmission rate within 30 d, length of hospitalization, hospitalization costs, or reoperation rate after IR between the two groups. However, patients in the LIR group more frequently required lysis of adhesions as compared to those in the OIR group (87.5% vs 41.7%, respectively, P < 0.05). Notably, following exclusion of patients who underwent enterectomy plus IR, OIR was more advantageous in terms of postoperative recovery of gastrointestinal function and hospitalization costs. CONCLUSION: The safety and feasibility of LIR for the treatment of CD are comparable to those of OIR with no increase in intraoperative or postoperative complications.

Laparoscopy for Crohn's disease: A comprehensive exploration of minimally invasive surgical techniques.

BACKGROUND: Along with the unceasing progress of medicine, Crohn's disease (CD), especially complex CD, is no longer a taboo for minimally invasive surgery. However, considering its special disease characteristics, more clinical trials are needed to confirm the safety and feasibility of laparoscopic surgery for CD. AIM: To investigate the safety and feasibility of laparoscopic enterectomy for CD, assess the advantages of laparoscopy over laparotomy in patients with CD, and discuss comprehensive minimally invasive surgical techniques in complex CD. METHODS: This study prospectively collected clinical data from patients with CD who underwent enterectomy from January 2017 to January 2020. It was registered in the Chinese clinical trial database with the registration number ChiCTR-INR-16009321. Patients were divided into a laparoscopy group and a traditional laparotomy group according to the surgical method. The baseline characteristics, operation time, intraoperative blood loss, temporary stoma, levels of abdominal adhesion, pathological characteristics, days to flatus and soft diet, postoperative complications, hospitalization time, readmission rate within 30 d, and hospitalization cost were compared between the two groups. RESULTS: A total of 120 eligible patients were enrolled into the pre-standardized groups, including 100 in the laparoscopy group and 20 in the laparotomy group. Compared with the laparotomy group, the postoperative hospitalization time in the laparoscopy group was shorter (9.1 ± 3.9 d vs 11.0 ± 1.6 d, P < 0.05), the days to flatus were fewer (2.8 ± 0.8 d vs 3.5 ± 0.7 d, P < 0.05), the days to soft diet were fewer (4.2 ± 2.4 d vs 6.2 ± 2.0 d, P < 0.05) and the intraoperative blood loss was less (103.3 ± 80.42 mL vs 169.5 ± 100.42 mL, P < 0.05). There were no statistically significant differences between the two groups in preoperative clinical data, operation time (149.0 ± 43.8 min vs 159.2 ± 40.0 min), stoma rate, levels of abdominal adhesion, total cost of hospitalization, incidence of postoperative complications [8.0% (8/100) vs 15.0% (3/20)], or readmission rate within 30 days [1.0% (1/100) vs 0.00 (0/20)]. CONCLUSION: Compared with laparotomy, laparoscopic enterectomy promotes the recovery of gastrointestinal function, shortens the postoperative hospitalization time, and does not increase the incidence of postoperative complications. Laparoscopic enterectomy combined with varieties of minimally invasive surgical techniques is a safe and acceptable therapeutic method for CD patients with enteric fistulas.

The NmrA-like family domain containing 1 pseudogene Loc344887 is amplified in gallbladder cancer and promotes epithelial-mesenchymal transition.

The expression pattern and biological role of long non-coding RNA (lncRNA) in cancer has been reported to be involved in many cancers. Here, we report the expression and biological role of a newly discovered lncRNA NmrA-like family domain containing 1 pseudogene (Loc344887) in gallbladder cancer (GBC). In this study, we found that the expression of Loc344887 was significantly elevated in GBC tissues and cell lines when compared with matched normal tissues and normal epithelial bile duct cell line, respectively. High Loc344887 was associated with larger tumor size. Loc344887 was upregulated significantly after ectopic expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in GBC cells. Downregulation of Loc344887 in GBC cells suppressed cell proliferation, blocked cells in G0/S phase, and decreased the migration and invasion cell numbers. In addition, downregulation of Loc344887 decreased the expression of transcription factor Twist, mesenchymal marker Vimentin, and N-cadherin and increased the expression of epithelial maker E-cadherin, which could prompt a mesenchymal-to-epithelial transition phenotype. These results demonstrated that Loc344887 might contribute to cell proliferation and epithelial-to-mesenchymal transition process in GBC, which might be a potential therapeutic target.

Long non-coding RNA H19 regulates FOXM1 expression by competitively binding endogenous miR-342-3p in gallbladder cancer.

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.

Overexpression of LncRNA-ROR predicts a poor outcome in gallbladder cancer patients and promotes the tumor cells proliferation, migration, and invasion.

LncRNA-ROR has been reported to be involved in many kinds of human cancers. However, whether LncRNA-ROR is involved in gallbladder cancer progression remains largely unknown. The objective of this study is to investigate the role of LncRNA-ROR in gallbladder cancer. We found that LncRNA-ROR expression level was upregulated in gallbladder cancer tissues (P < 0.05) and was significantly associated with tumor sizes (P < 0.05) and lymph node metastasis (P < 0.05). High expression of LncRNA-ROR was significantly associated with poor prognosis in gallbladder cancer patients (P < 0.05). Moreover, knockdown of LncRNA-ROR inhibited cell proliferation, migration, and invasion. The epithelial-mesenchymal transition (EMT) phenotype induced by TGF-ß1 was reversed after LncRNA-ROR knocking down in SGC-996 and Noz cells. LncRNA-ROR plays an important role in the development of gallbladder cancer and mediates the EMT in gallbladder cancer. LncRNA-ROR might act as a marker of prognosis and therapeutic target for gallbladder cancer.

The lncRNA MALAT1 functions as a competing endogenous RNA to regulate MCL-1 expression by sponging miR-363-3p in gallbladder cancer.

Gallbladder carcinoma (GBC) is an aggressive neoplasm, and the treatment options for advanced GBC are limited. Recently, long non-coding RNAs (lncRNAs) have emerged as new gene regulators and prognostic markers in several cancers. In this study, we found that metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) expression was up-regulated in GBC tissues (P < 0.05). Luciferase reporter assays and RNA pull down assays showed that MALAT1 is a target of miR-363-3p. Real-time quantitative PCR and Western blot analysis indicated that MALAT1 regulated Myeloid cell leukaemia-1 (MCL-1) expression as a competing endogenous RNA (ceRNA) for miR-363-3p in GBC cells. Furthermore, MALAT1 silencing decreased GBC cell proliferation and the S phase cell population and induced apoptosis in vitro. In vivo, tumour volumes were significantly decreased in the MALAT1 silencing group compared with those in the control group. These data demonstrated that the MALAT1/miR-363-3p/MCL-1 regulatory pathway controls the progression of GBC. Inhibition of MALAT1 expression may be to a novel therapeutic strategy for gallbladder cancer.

Down-regulation of Transducin-Like Enhancer of Split protein 4 in hepatocellular carcinoma promotes cell proliferation and epithelial-Mesenchymal-Transition.

BACKGROUND: Transducin-Like Enhancer of Split protein 4 (TLE4) has been reported to be involved in some subsets of acute myeloid leukemia and colorectal cancer. In the present study, we aimed to explore the role of TLE4 in tumorigenesis and cancer progression in hepatocellular carcinoma (HCC). METHODS: The expression pattern of TLE4 in HCC was determined by Western-blot and qRT-PCR, gain-of-function and loss-of-function was used to explore the biological role of TLE4 in HCC cells. A xenograft model was established to confirm its effects on proliferation. RESULTS: The protein expression levels of TLE4 were significantly down-regulated in HCC tissues compared to matched adjacent normal liver tissues. In vitro, down-regulation of TLE4 in Huh7 or SMMC-7721 promoted cell proliferation and ectopical expression of TLE4 in Hep3B or Bel-7404 suppressed cell proliferation. In addition, the cell colony formation ability was enhanced after down-regulation of TLE4 expression in Huh-7 but suppressed after over-expression in Hep3B. Furthermore, down-regulation of TLE4 increased the cell invasion ability, as well as increased the expression level of Vimentin and decreased that of E-cadherin, indicating a phenotype of epithelial-mesenchymal transition (EMT) in HCC cells. On the contrary, ectopical expression of TLE4 in HCC cells decreased the cell invasion ability and inhibited EMT. In vivo, compared to control group, xenograft tumor volumes were significantly decreased in TLE4 overexpression group. CONCLUSIONS: These results demonstrated that TLE4 might play important regulatory roles in cellular proliferation and EMT process in HCC.

Long non-coding RNA MINCR promotes gallbladder cancer progression through stimulating EZH2 expression.

The regulation of MYC-regulated long non-coding RNAs has been reported to contribute to certain types of cancers. However, the role of MYC-induced long non-coding RNA (MINCR) in the tumorigenesis of gallbladder cancer (GBC) is still largely unknown. In this study, we discovered that MINCR was markedly upregulated in GBC tissues compared with adjacent normal tissues. High MINCR expression levels in GBC were positively associated with tumor volume and lymph node metastasis and were negatively correlated with overall survival (OS). Upregulation of MINCR and enhancer of zeste homolog 2 (EZH2) in GBC coincided with the downregulation of miR-26a-5p in GBC. Mechanistically, MINCR/miR-26a-5p/EZH2 axis was found to be involved in cell proliferation, cell invasive and apoptosis in GBC cells. Moreover, knockdown of MINCR suppressed cell proliferation, decreased S-phase cell numbers, increased cell apoptosis, and inhibited cell invasion by inhibiting the epithelial-mesenchymal transition (EMT) phenomenon in GBC cells. In vivo, tumor volumes were significantly decreased in the MINCR silencing group compared with those in the control group. These results demonstrated that MINCR could potentially be a therapeutic target as well as a prognostic marker in GBC.

Erratum: Upregulation of H19 indicates a poor prognosis in gallbladder carcinoma and promotes epithelial-mesenchymal transition.

[This corrects the article on p. 15 in vol. 6, PMID: 27073719.].

Long non-coding RNA Malat1 promotes gallbladder cancer development by acting as a molecular sponge to regulate miR-206.

Long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (Malat1) functions as an oncogene in many types of human cancer. In this study, we show that Malat1 is overexpressed in gallbladder cancer (GBC) tissue and cells. The high Malat1 levels correlated positively with tumor size and lymphatic metastasis, and correlated negatively with overall survival. We also show that Malat1 functions as a competing endogenous RNA (ceRNA) for miR-206. Because miR-206 directly suppresses expression of ANXA2 and KRAS, which are thought to promote GBC progression, Malat1 binding of miR-206 in GBC tissue and cells has an oncogenic effect. Conversely, Malat1 knockdown inhibits proliferation and invasion by GBC cells while increasing apoptosis. In vivo, silencing Malat1 decreases tumor volume. These results suggest Malat1 could potentially serve as a therapeutic target and prognostic marker for GBC.

Upregulation of H19 indicates a poor prognosis in gallbladder carcinoma and promotes epithelial-mesenchymal transition.

The imprinted oncofetal long non-coding RNA H19 has been reported to be involved in many kinds of human cancers. However, whether lncRNA H19 implicate in oncogenesis and cancer progression in gallbladder cancer remain largely unknown. In the present study, compared with adjacent normal tissues, the level of H19 was significantly upregulated in gallbladder cancer tissues and was positively associated with lymphatic metastasis and tumor size. The overall survival is shorter in those who had higher H19 expression among GBC patients. In vitro, both TGF-ß1 and IL-6 treatment induced upregulation of H19, downregulated the protein level of E-cadherin while increased Vimentin, indicating an epithelial-mesenchymal transition (EMT) phenotype in GBC. The overexpression of H19 in GBC cells enhanced tumor invasion and promoted EMT by upregulated transcription factor Twist1. On the contrary, Loss of function studies indicated that H19 interference in GBC suppressed tumor cell invasion and promoted mesenchymal-epithelial transition (MET) via suppressing Twist expression. In vivo, the volume of the tumors in H19-inteference group was significantly decreased compared to those in the control group of nude mice. Both western-blot and immunohistochemistry confirmed that a MET phenotype existed in the H19 interference group when compared to control group. These results defined H19 as a novel prognostic factor for GBC, and indicated that it might play important regulatory roles in the EMT process.

Long noncoding RNA H19 contributes to gallbladder cancer cell proliferation by modulated miR-194-5p targeting AKT2.

Gallbladder cancer (GBC) is a highly malignant cancer with poor prognosis. Although long noncoding RNA (lncRNA) H19 has been reported to play vital role in many human cancers, whether it is involved in GBC proliferation is still unknown. This study was designed to explore the effect of H19 in GBC cell proliferation. The expression of H19 and AKT2 were significantly elevated in GBC tissues, and the level of miR-194-5p is markedly decreased. Moreover, the RNA levels of H19 and AKT2 were positively correlated, and H19 elevation was significantly associated with tumor size. Cell proliferation decreased significantly after knockdown of H19 in GBC-SD and NOZ cells and after knockdown of AKT2 in NOZ cells. Results from cell cycle studies indicated that the S phase were significantly decreased after knockdown of H19 in NOZ cells but significantly elevated after overexpression of H19 in GBC-SD cells. Furthermore, knockdown of H19 upregulated miR-194-5p levels, yet significantly decreased miR-194-5p targeting AKT2 gene expression in NOZ cells. Inhibitor against miR-194-5p reversed these effects. In addition, overexpression of H19 in GBC-SD cells downregulated miR-194-5p and markedly increased AKT2 expression, and miR-194-5p mimic reversed these effects. Eventually, GBC cells were arrested in G0/G1-phase after H19 knockdown, inhibition of miR-194-5p markedly promoted cells into S-phase and co-transfection of siH19, and miR-194-5p inhibitor exerted mutually counter-regulated effects on cell cycle. These results suggested that H19/miR-194-5p/AKT2 axis regulatory network might modulate cell proliferation in GBC.