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Metastasis is a well-known poor prognostic factor in cancer. However, the mechanisms how long non-coding RNAs (lncRNAs) regulate metastasis in colorectal cancer (CRC) remain largely unknown. Besides, tumor-associated macrophages (TAMs) play an important role in tumor progression, yet the contribution of lncRNA-mediated crosstalk between TAMs and CRC cells to tumor progression is not well understood. In this study, we report that lncRNA RPPH1 was significantly upregulated in CRC tissues, and the RPPH1 overexpression was associated with advanced TNM stages and poor prognosis. RPPH1 was found to promote CRC metastasis in vitro and in vivo. Mechanistically, RPPH1 induced epithelial–mesenchymal transition (EMT) of CRC cells via interacting with β-III tubulin (TUBB3) to prevent its ubiquitination. Furthermore, CRC cell-derived exosomes transported RPPH1 into macrophages which mediate macrophage M2 polarization, thereby in turn promoting metastasis and proliferation of CRC cells. In addition, exosomal RPPH1 levels in blood plasma turned out to be higher in treatment-naive CRC patients but lower after tumor resection. Compared to CEA and CA199, exosomal RPPH1 in CRC plasma displayed a better diagnostic value (AUC = 0.86). Collectively, RPPH1 serves as a potential therapeutic and diagnostic target in CRC.

BackgroundStrictures are common complications after ileal pouch surgery. The aim of this study is to evaluate the efficacy and safety of endoscopic stricturotomy vs. endoscopic balloon dilation (EBD) in the treatment of pouch inlet strictures.MethodsAll consecutive ulcerative colitis patients with the diagnosis of pouch inlet or afferent limb strictures treated in our Interventional Inflammatory Bowel Disease Unit (i-IBD) from 2008 to 2017 were extracted. The primary outcomes were surgery-free survival and post-procedural complications.ResultsA total of 200 eligible patients were included in this study, with 40 (20.0%) patients treated with endoscopic stricturotomy and 160 (80.0%) patients treated with EBD. Symptom improvement was recorded in 11 (42.3%) patients treated with endoscopic stricturotomy and 16 (13.2%) treated with EBD. Subsequent surgery rate was comparable between the two groups (9 [22.5%] vs. 33 [20.6%], P = 0.80) during a median follow-up of 0.6 years (interquartile range [IQR] 0.4–0.8) vs. 3.6 years (IQR 1.1–6.2) in patients receiving endoscopic stricturotomy and EBD, respectively. The overall surgery-free survival seems to be comparable as well (P = 0.12). None of the patients in the stricturotomy group developed pouch failure, while 9 patients (5.6%) had pouch failure in the balloon dilation group (P = 0.17). Procedural bleeding was seen in three occasions (4.7% per procedure) in patients receiving endoscopic stricturotomy and perforation was seen in three occasions (0.8% per procedure) in patients receiving EBD (P = 0.02). In multivariable analysis, an increased length of the stricture (hazard ratio [HR] 1.4, 95% confidence interval [CI] 1.0–1.8) and concurrent pouchitis (HR 2.5, 95% CI 1.0–5.7) were found to be risk factors for the requirement of surgery.ConclusionEndoscopic stricturotomy and EBD were both effective in treating patients with pouch inlet or afferent limb strictures, EBD had a higher perforation risk while endoscopic stricturotomy had a higher bleeding risk.

Background Constitutive activation of nuclear factor-κB (NF-κB) signaling plays a key role in the development and progression of colorectal carcinoma (CRC). However, the underlying mechanisms of excessive activation of NF-κB signaling remain largely unknown. Methods We used high throughput RNA sequencing to identify differentially expressed circular RNAs (circRNAs) between normal human intestinal epithelial cell lines and CRC cell lines. The identification of protein encoded by circPLCE1 was performed using LC–MS. The function of novel protein was validated in vitro and in vivo by gain or loss of function assays. Mechanistic results were concluded by immunoprecipitation analyses. Results A novel protein circPLCE1-411 encoded by circular RNA circPLCE1 was identified as a crucial player in the NF-κB activation of CRC. Mechanistically, circPLCE1-411 promoted the ubiquitin-dependent degradation of the critical NF-κB regulator RPS3 via directly binding the HSP90α/RPS3 complex to facilitate the dissociation of RPS3 from the complex, thereby reducing NF-κB nuclear translocation in CRC cells. Functionally, circPLCE1 inhibited tumor proliferation and metastasis in CRC cells, as well as patient-derived xenograft and orthotopic xenograft tumor models. Clinically, circPLCE1 was downregulated in CRC tissues and correlated with advanced clinical stages and poor survival. Conclusions circPLCE1 presents an epigenetic mechanism which disrupts NF-κB nuclear translocation and serves as a novel and promising therapeutic target and prognostic marker.

AimThe impact of pelvis on the development of anastomotic leak (AL) in rectal cancer (RC) patients who underwent anterior resection (AR) remains unclear. The aim of this study was to evaluate the impact of pelvic dimensions on the risk of AL.MethodsA total of 1058 RC patients undergoing AR from January 2013 to January 2016 were enrolled. Pelvimetric parameters were obtained using abdominopelvic computed tomography scans.ResultsUnivariate analyses showed that pelvic inlet, pelvic outlet, interspinous distance, and intertuberous distance were significantly associated with the risk for AL (P < 0.05). Multivariate analysis confirmed that pelvic inlet and intertuberous distance were independent risk factors for AL (P < 0.05). Significant factors from multivariate analysis were assembled into the nomogram A (without pelvic dimensions) and nomogram B (with pelvic dimensions). The area under curve (AUC) of nomogram B was 0.72 (95% CI 0.67–0.77), which was better than the AUC of nomogram A (0.69, [95% CI 0.65–0.74]), but didn’t reach a statistical significance (P = 0.199). Decision curve supported that nomogram B was better than nomogram A.ConclusionPelvic dimensions, specifically pelvic inlet and intertuberous distance, seemed to be independent predictors for postoperative AL in RC patients. Pelvic inlet and intertuberous distance incorporated with preoperative radiotherapy, preoperative albumin, conversion, and tumor diameter in the nomogram might provide a clinical tool for predicting AL.

Xihuang pill, an approved Chinese medicine formula (state medical permit number. Z11020073), is a commonly used adjuvant drug for cancer patients in China. Xihuang pill has a satisfactory effect in treating breast cancer in clinics, especially triple-negative breast cancer (TNBC), which is the most aggressive type of breast cancer, and finite effective therapies. However, the mechanism of Xihuang pill in treating TNBC remains unclear. The present study aims to explore the pharmacological mechanism of Xihuang pill in treating advanced TNBC. We identified the main chemical components of Xihuang pill by using HPLC-Q-TOF-MS/MS. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis shows that serum containing Xihuang pill (XS) had no obvious killing effect on any subtype of breast cancer cells, but it inhibited mammosphere colony formation of two TNBC cell lines (4T1 and HCC1806 cells) and could enhance the inhibitory effect of paclitaxel (PTX) on the proliferation of 4T1 and HCC1806 cells when combined with PTX. Seventy-six active compounds in Xihuang pill, their 300 protein targets, and 16667 TNBC stem cell–related genes were identified. The drug–herb–active compound–target gene–disease network and enrichment analyses were constructed with 190 overlapping candidate targets. Through text mining and molecular docking, the target gene NR3C2 and its active compound naringenin were selected for further validation. According to the TCGA database, we observed that a high expression of NR3C2 promoted a higher survival probability regarding overall survival (OS). In vitro experiments indicated that naringenin presented an identical effect to XS, possibly by regulating the NR3C2 expression. Overall, this study explored the effect of Xihuang pill in treating advanced TNBC cells and showed that naringenin, which is the key active compound of Xihuang pill, could lessen the stemness of TNBC cells to produce a synergistic effect on PTX by regulating the NR3C2 gene.

Abstract Background Clostridium difficile infection (CDI) is traditionally considered a colon-affecting disease with frequent pseudomembrane formation. However, multiple case reports have documented the existence of CDI in the small bowel, and the literature on outcome of C difficile enteropathy (CDE) is sparse. The aims of our study are to identify risk factors and to assess patient-related outcomes associated with CDE. Methods This is a case-control study involving 112 patients at our tertiary care center. Patients with an ileostomy who tested positive for C difficile toxins were assigned to the study group (n = 34). The control group included patients with an ileostomy who tested negative for the C difficile toxins (n = 78). Via chart review, we collected data on baseline characteristics, laboratory values, potential risk factors, and outcome measures. Results Patients in the study and control groups were comparable in baseline and laboratory characteristics. In univariate analysis, CDE was associated with a history of smoking (hazard ratio [HR], 2.1; 95% confidence interval [CI], 1.06-4.3; P = 0.034), the presence of alcohol use (HR, 3.7; 95% CI, 1.05-12.8; P = 0.042), and older median age at the time of ileostomy (HR, 1.2; 95% CI, 1.07-1.3; P = 0.001). In multivariate analysis, no significant association between established CDI risk factors (eg, prior exposure to antibiotics and the use of proton pump inhibitors or histamine 2 receptor blockers) and the risk for the CDE was found. Only a history of alcohol intake was found to be associated with CDE (HR, 3.9; 95% CI, 1.09-14.1; P = 0.036). No significant difference in mortality was found in the study and control groups (2.9% vs 1.3%, P = 0.52), but patients with CDE were more likely to have acute kidney injury (AKI) than those without CDE (odds ratio, 4.0; 95% CI, 1.2-13.0. P = 0.023). Conclusions We identified a history of alcohol use a risk factor for CDE. Furthermore, CDE was found be associated with an increased risk for developing AKI.

Patients with inflammatory bowel disease (IBD) are at a higher risk of developing colitis-associated colorectal cancer. The aim of the present study was to investigate the role of CD73 in IBD-associated tumorigenesis. A mouse model of colitis-associated tumorigenesis (CAT) induced by azoxymethane and dextran sulfate sodium was successfully constructed. Model mice were injected with CD73 inhibitor or adenosine receptor agonist. Colon length, body weight loss and tumor formation were assessed macroscopically. Inflammatory cytokine measurement and RNA sequencing on colon tissues were performed. Inhibition of CD73 by adenosine 5′-(α,β-methylene) diphosphate (APCP) suppressed the severity of CAT with attenuated weight loss, longer colons, lower tumor number and smaller tumor size compared with the model group. Activation of adenosine receptors using 1-(6-amino-9H-purin-9-yl)-1-deoxy-N-ethyl-β-D-ribofuranuronamide (NECA) exacerbated CAT. Histological assessment indicated that inhibition of CD73 reduced, while activation of adenosine receptors exacerbated, the histological damage of the colon. Increased expression of pro-inflammatory cytokines (tumor necrosis factor-α and interleukin-6) in colonic tissue was detected in the NECA group. According to RNA sequencing results, potential oncogenes such as arachidonate 15-lipoxygenase (ALOX15), Bcl-2-like protein 15 (Bcl2l15) and N-acetylaspartate synthetase (Nat8l) were downregulated in the APCP group and upregulated in the NECA group compared with the model group. Therefore, inhibition of CD73 attenuated IBD-associated tumorigenesis, while activation of adenosine receptors exacerbated tumorigenesis in a C57BL/6J mouse model. This effect may be associated with the expression of pro-inflammatory cytokines and the regulation of ALOX15, Bcl2l15 and Nat8l.

Continent ileostomy (CI) was once a prevalent surgical technique for patients who required total proctocolectomy but then gave way to ileal pouch-anal anastomosis (IPAA) after 1980. Although IPAA has been the gold standard procedure preferred by most patients when total proctocolectomy is required, due to its imitation of physiological function of rectum and preserved function of anus, various complications have been observed with a relatively high rate of morbidity that could affect pouch longevity. Once serious complications such as pelvic abscesses and/or fistula occur, the pouch often needs to be removed. In addition, for some patients with a shortened small intestine or foreshortened mesentery, it is impossible for the ileal pouch to reach the pelvic floor, thus making the creation of an IPAA difficult. Previously, most of these patients would be referred for an end ileostomy, with an associated poor quality of life. In this circumstance, we propose that CI may deserve a reappraisal and serve as an alternative. In this article, we review the indications, contraindications, technique evolution, and outcomes of CI.

Objective The objective of this study was to evaluate the efficacy of stricturoplasty and endoscopic balloon dilatation in the treatment for ileal pouch strictures. Method Consecutive inflammatory bowel disease patients with pouch strictures seen at our Pouch Center from 2002 to 2012 were studied. The efficacy and safety of stricturoplasty (vs. endoscopic balloon dilation) were evaluated with both univariate and multivariate analyses. Results A total of 167 patients met the inclusion criteria, including 16 (9.6 %) with surgical stricturoplasty and 151 (90.4 %) with endoscopic balloon dilation. Ninety-four patients (56.3 %) were male, with a mean age at the diagnosis of pouch stricture of 41.6 ± 13.2 years. Fifty-one patients (30.5 %) had multiple pouch strictures, while 100 (59.9 %) patients had strictures at the pouch inlet. The mean length of pouch strictures was 1.2 ± 0.6 cm. No difference was found between the stricturoplasty and endoscopic dilation groups in clinicopathological variables, except for the degree of strictures ( p  = 0.019). After a mean follow-up of 4.1 ± 2.6 years, pouch stricture recurred in 92 patients (55.1 %) and 21 (12.6 %) patients developed pouch failure. The time interval between the procedure and pouch stricture recurrence or pouch failure was longer in the stricturoplasty group than that in the endoscopic dilation group ( p  < 0.001). Patients in the two groups had similar overall pouch survival rates and stricture-free survival rates. In the multivariate analysis, stricturoplasty vs. endoscopic dilation was not significantly associated with either overall pouch survival or stricture-free survival. There was no difference in the procedure-associated complication rates between the two groups. Conclusion Surgical stricturoplasty and endoscopic dilation treatment are complimentary techniques for pouch strictures. Repeated endoscopic dilatations are often required, while surgical stricturoplasty appeared to yield a longer time interval to stricture recurrence or pouch failure.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.An amendment to this paper has been published and can be accessed via a link at the top of the paper.