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Purpose This study aimed to evaluate the image quality and diagnostic value of compressed sensing-sensitivity encoding (CS-SENSE) accelerated 3-dimensional (3D) T2-weighted turbo spin-echo (T2W TSE) sequence in patients with rectal cancer compared with conventional 3D and 2-dimensional (2D) sequences. Methods A total of 54 patients who underwent the above three sequences were enrolled. Two radiologists independently reviewed the image quality using an ordinal 5-point Likert scale. The quantitative measurement was performed to calculate the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). The diagnostic value was assessed using TN staging, extramural vascular invasion and mesorectal fascia status. Friedman and McNemar’s tests were applied for comparative analysis. Results Forty-two patients were successfully included. Compared with 3D and 2D sequences, the CS-SENSE 3D sequence speeded up by 39% and 23%, respectively. The edge sharpness of CS-SENSE 3D images was similar to that of 3D and 2D images. The noise of CS-SENSE 3D images was comparable to that of 3D images but higher than that of 2D images. The SNRtumor and SNRrectal wall of CS-SENSE 3D images were considerably lower than those of 3D and 2D images. The CNR of CS-SENSE 3D images was similar to that of 3D images but lower than that of 2D images. However, no considerable differences were noted in diagnostic value among the three sequences. Conclusions CS-SENSE 3D T2 sequence provided comparable diagnostic performance, with substantially reduced imaging time and no significant sacrifices in image quality. This technique may serve as a reliable tool for evaluating rectal cancer. Graphical abstract

Recently, serum exosomal circular RNAs (circRNAs) were applied to discriminate cancer patients from healthy individuals, indicating that exosomal circRNAs have the potential to be novel biomarkers for cancer diagnosis. This study aims to summarize the role of exosomal circRNAs in cancer diagnosis by a meta-analysis.A comprehensive literature search was conducted up to July 2021 in PubMed, Web of Science, EMBASE, and Cochrane Database. To evaluate the diagnostic value, the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were pooled. Threshold effect followed by subgroup analysis and meta-regression were performed to explore the source of heterogeneity. Sensitivity analysis was performed to assess the stability of this meta-analysis model. Fagan plots and likelihood ratio scattergrams were used to explore the potential clinical significance.Ten eligible studies with 514 controls and 557 patients were included in this diagnostic meta-analysis. The pooled sensitivity, specificity, PLR, NLR, and DOR were 0.75 (95% CI: 0.65-0.83), 0.84 (95% CI, 0.78-0.89), 5.87 (95% CI, 3.67-9.38), 0.28 (95% CI, 0.19-0.40), and 21.15 (95% CI, 10.25-43.68), respectively. The AUC was 0.89 (95% CI, 0.86-0.91). Sensitivity analysis showed that four studies had an impact on the pooled results and mainly contributed to the heterogeneity. Fagan's nomogram revealed that the prior probability of 20%, the post probability positive, the post probability negative were 59% and 6%, respectively.Our results suggested that exosomal circRNAs might serve as powerful biomarkers in detecting cancers with high sensitivity and specificity. However, more well-designed and multicenter diagnostic tests are needed to validate our results.

Protein citrullination, including histone H1 and H3 citrullination, is important for transcriptional regulation, DNA damage response, and pluripotency of embryonic stem cells (ESCs). Tripartite motif containing 28 (Trim28), an embryonic development regulator involved in ESC self-renewal, has recently been identified as a novel substrate for citrullination by Padi4. However, the physiological functions of Trim28 citrullination and its role in regulating the chromatin structure and gene transcription of ESCs remain unknown. In this paper, we show that Trim28 is specifically citrullinated in mouse ESCs (mESCs), and that the loss of Trim28 citrullination induces loss of pluripotency. Mechanistically, Trim28 citrullination enhances the interaction of Trim28 with Smarcad1 and prevents chromatin condensation. Additionally, Trim28 citrullination regulates mESC pluripotency by promoting transcription of Nanog and Klf4 which it does by increasing the enrichment of H3K27ac and H3K4me3 and decreasing the enrichment of H3K9me3 in the transcriptional regulatory region. Thus, our findings suggest that Trim28 citrullination is the key for the epigenetic activation of pluripotency genes and pluripotency maintenance of ESCs. Together, these results uncover a role Trim28 citrullination plays in pluripotency regulation and provide novel insight into how citrullination of proteins other than histones regulates chromatin compaction.

Background This study aims to determine the real incidence of pericolic lymph nodes metastasis beyond 10 cm proximal to the tumor (pPCN) and its prognostic significance in rectal cancer patients. Methods Consecutive patients with rectal cancer underwent curative resection between 2015 and 2017 were included. Margin distance was marked and measured in vivo and lymph nodes were harvested on fresh specimens. Clinicopathological characteristics and oncological outcomes (3-year overall survival (OS) and disease-free survival (DFS)) were analyzed between patients with pPCN and patients without pPCN (nPCN). Results There were 298 patients in the nPCN group and 14 patients (4.5%) in pPCN group. Baseline characteristics were balanced except more patients received preoperative or postoperative chemoradiotherapy in pPCN group. Preoperative more advanced cTNM stage (log-rank p = 0.005) and intraoperative more pericolic lymph nodes beyond 10 cm proximal to the tumor (PCNs) (log-rank p = 0.002) were independent risk factors for pPCN. The maximum short-axis diameter of mesenteric lymph nodes ≥8 mm was also contributed to predicting the pPCN. pPCN was an independent prognostic indicator and associated with worse 3-year OS (66% vs 91%, Cox p = 0.033) and DFS (58% vs 92%, Cox p = 0.012). Conclusion The incidence of pPCN was higher than expected. Patients with high-risk factors (cTNM stage III or more PCNs) might get benefits from an extended proximal bowel resection to avoid residual positive PCNs.

Lysophosphatidic acid receptor 6 (LPAR6) is a G protein–coupled receptor that plays critical roles in cellular morphology and hair growth. Although LPAR6 overexpression is also critical for cancer cell proliferation, its role in liver cancer tumorigenesis and the underlying mechanism are poorly understood. Here, using liver cancer and matched paracancerous tissues, as well as functional assays including cell proliferation, quantitative real-time PCR, RNA-Seq, and ChIP assays, we report that LPAR6 expression is controlled by a mechanism whereby hepatocyte growth factor (HGF) suppresses liver cancer growth. We show that high LPAR6 expression promotes cell proliferation in liver cancer. More importantly, we find that LPAR6 is transcriptionally down-regulated by HGF treatment and that its transcriptional suppression depends on nuclear receptor coactivator 3 (NCOA3). We note that enrichment of NCOA3, which has histone acetyltransferase activity, is associated with histone 3 Lys-27 acetylation (H3K27ac) at the LPAR6 locus in response to HGF treatment, indicating that NCOA3 transcriptionally regulates LPAR6 through the HGF signaling cascade. Moreover, depletion of either LPAR6 or NCOA3 significantly inhibited tumor cell growth in vitro and in vivo (in mouse tumor xenograft assays), similar to the effect of the HGF treatment. Collectively, our findings indicate an epigenetic link between LPAR6 and HGF signaling in liver cancer cells, and suggest that LPAR6 can serve as a biomarker and new strategy for therapeutic interventions for managing liver cancer.

Colorectal cancer (CRC) is one of the most common malignant tumours, with multiple driving factors and biological transitions involved in its development. Claudin‐2 (CLDN2), a well‐defined component of cellular tight junction, has been indicated to associate with CRC progression. However, the function of CLDN2 and the underlying mechanism whereby the downstream signalling transduction is regulated in CRC remains largely unclear. In this study, we demonstrated that CLDN2 is upregulated in CRC samples and associated with poor survival. And CLDN2 depletion significantly promotes N‐myc downstream‐regulated gene 1 (NDRG1) transcription, leading to termination of the CRC growth and metastasis in vitro and in vivo. Mechanistically, this process promotes CLDN2/ZO1/ZONAB complex dissociation and ZONAB shuttle into nucleus to enrich in the promoter of NDRG1. Thus, this study reveals a novel CLDN2/ZO1/ZONAB‐NDRG1 axis in CRC by regulating the expression of EMT‐related genes and CDKIs, suggesting CLDN2 may serve as a promising target for CRC treatment., CLDN2/ZO1/ZONAB‐NDRG1 axis in CRC regulate EMT and cell proliferationDownregulation of CLDN2 promotes ZONAB relocation to nucleus and NDRG1 transcription2

Colorectal cancer (CRC) is one of the most common malignant tumors in the world. CRC recurrence and metastasis cause poor prognosis. ANGPTLs (angiopoietin-like proteins) are a family of proteins that are widely involved in metabolic disease and tumorigenesis. The roles of ANGPTLs in CRC are still controversial and deserve further research. In this study, several databases were employed to explore the expression profiles, prognostic values, genetic alterations, potential biological function, and immune infiltration correlation of ANGPTLs in CRC. The expression of ANGPTL4 was significantly positively correlated with the stage of CRC. Therefore, cell and molecular experiments were further performed to explore the roles of ANGPTL4. Our results showed that the transcriptions of ANGPTLs in colon cancer and rectal cancer tissues were lower than those in normal tissues, but the protein expression varied among different ANGPTLs. In addition, the high expression of ANGPTLs led to a relatively poor oncological outcome. Specifically, the expression of ANGPTL4 is significantly positively correlated with the stage of CRC. Further investigation revealed that ANGPTLs are mainly involved in signal transduction and the regulation of transcription, while KEGG pathway analyses demonstrated pathways in cancer. Additionally, we also observed that ANGPTL4 could promote the proliferation and migration of CRC cells, and four specific small molecule compounds had potential ANGPTL4-binding capabilities, suggesting the clinical application of these small molecule compounds on CRC treatment. Our findings imply the prognostic values and potential therapeutic targets of ANGPTLs in CRC.

Exosomes or other extracellular vesicles released from cells play an important role in cell-to-cell communication by transferring bio-information (DNA, coding/non-coding RNA, and proteins), which indicates parental cell status to recipient cells in the extracellular environment. Increasingly, evidence shows that tumor-derived exosomes mediate tumor pre-metastatic niche (PMN) remodeling to establish a supportive and receptive niche to promote tumor cell colonization and metastasis. Uptake of genetic information by target cells in the extracellular environment triggers epigenetic changes that contribute to PMN formation. Here, we provide a comprehensive overview of the current understanding of exosomes-mediated reprogramming of cells in PMN formation.

BackgroundMagnetic resonance imaging (MRI)-based lymph node staging remains a significant challenge in the treatment of rectal cancer. Pretreatment evaluation of lymph node metastasis guides the formulation of treatment plans. This systematic review aimed to evaluate the diagnostic performance of MRI in lymph node staging using various morphological criteria.MethodsA systematic search of the EMBASE, Medline, and Cochrane databases was performed. Original articles published between 2000 and January 2021 that used MRI for lymph node staging in rectal cancer were eligible. The included studies were assessed using the QUADAS-2 tool. A bivariate random-effects model was used to conduct a meta-analysis of diagnostic test accuracy.ResultsThirty-seven studies were eligible for this meta-analysis. The pooled sensitivity, specificity, and diagnostic odds ratio of preoperative MRI for the lymph node stage were 0.73 (95% confidence interval [CI], 0.68–0.77), 0.74 (95% CI, 0.68–0.80), and 7.85 (95% CI, 5.78–10.66), respectively. Criteria for positive mesorectal lymph node metastasis included (A) a short-axis diameter of 5 mm, (B) morphological standard, including an irregular border and mixed-signal intensity within the lymph node, (C) a short-axis diameter of 5 mm with the morphological standard, (D) a short-axis diameter of 8 mm with the morphological standard, and (E) a short-axis diameter of 10 mm with the morphological standard. The pooled sensitivity/specificity for these criteria were 75%/64%, 81%/67%, 74%/79%, 72%/66%, and 62%/91%, respectively. There was no significant difference among the criteria in sensitivity/specificity. The area under the receiver operating characteristic (ROC) curve values of the fitted summary ROC indicated a diagnostic accuracy rate of 0.75–0.81.ConclusionMRI scans have minimal accuracy as a reference index for pretreatment staging of various lymph node staging criteria in rectal cancer. Multiple types of evidence should be used in clinical decision-making.

A first-line biologic treatment for metastatic colorectal cancer (mCRC) is still controversial. We, therefore, performed a meta-analysis to determine the efficacy of first-line cetuximab versus bevacizumab for RAS and BRAF wild-type mCRC. In March 2018, an electronic search of the following biomedical databases was performed: PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov and Web of Knowledge. Randomized controlled trials (RCTs) and prospective or observational cohort studies (OCSs) were included. Subgroup analyses of all RCTs were performed in all outcomes. All statistical analyses were performed using RevMan software 5.3. Two RCTs and three OCSs, involving a total 2576 patients, were included. The meta-analysis reported that cetuximab was associated with a longer overall survival (OS) [HR 0.89, 95% CI (0.81–0.98); p = 0.02], a higher ORR [RR 1.11, 95% CI (1.03–1.19); p = 0.006], higher complete response [RR 3.21, 95% CI (1.27–8.12); p = 0.01] and a greater median depth of response than bevacizumab. However, no significant difference was observed between cetuximab and bevacizumab groups for PFS, DCR, partial response, progressive disease, curative intent metastasectomy, EORR and incidence of grade 3 or higher adverse events. In the subgroup meta-analyses of the RCTs, inconsistent results compared to the main analysis, however, were found, in the ORR, DCR and curative intent metastasectomy. The current evidence indicates that compared to bevacizumab treatment, cetuximab provides a clinically relevant effect in first-line treatment against mCRC, at the cost of having lower stable disease.

CRL4, a well-defined E3 ligase, has been reported to be upregulated and is proposed to be a potential drug target in ovarian cancers. However, the biological functions of CRL4 and the underlying mechanism regulating cancer chemoresistance are still largely elusive. Here, we show that CRL4 is considerably increased in cisplatin-resistant ovarian cancer cells, and CRL4 knockdown with shRNAs is able to reverse cisplatin-resistance of ovarian cancer cells. Moreover, CRL4 knockdown markedly inhibits the expression of BIRC3, one of the inhibitors of apoptosis proteins (IAPs). Besides, lower expression level of BIRC3 is associated with better prognosis of ovarian cancer patients, and BIRC3 knockdown in ovarian cancer cells can recover their sensitivity to cisplatin. More importantly, we demonstrate that CRL4 regulates BIRC3 expression by mediating the STAT3, but not the PI3K pathway. Therefore, our results identified CRL4 as an important factor in ovarian cancer chemoresistance, suggesting that CRL4 and BIRC3 may serve as novel therapeutic targets for relapsed patients after treatment with cisplatin and its derivative to overcome the bottle neck of ovarian cancer chemoresistance.

Background: To explore the clinical characteristics, diagnosis and treatment of obturator hernia.Methods: Eighty-six patients who were diagnosed as obturator hernia by abdominal CT in the Department of Gastrointestinal Surgery of our hospital between 2009 and 2019 were enrolled in this study. Patient characteristics, surgical method, postoperative complications and mortalities were retrospectively reviewed, and the patients were followed by telephone or clinic visit to check for the recurrence.Results: 30 days mortality rate of 5.5% and 46.1% were observed in surgery group and non-surgery group, respectively. Surgery was performed as an emergency procedure in 59 cases and elective procedure in 14 cases depending on different hernia contents, intestinal necrosis and signs of peritonitis. In the emergency surgery group, segmental intestinal resection with anastomosis was performed in 24 patients(24/59, 40.7%). There were 4 deaths(4/59, 6.8%) in this group ,all of which occurred in patients undergoing SI resections. In contrast, no bowel resection, postoperative complications, or death occurred in the elective surgery group. 3 -year recurrence rates of 5.1% (3/59)and 7.1%(1/14) were observed in the emergency surgery and the elective surgery group, respectively. Conclusions: CT examination plays an important role in improving the diagnostic rate of obturator hernia. In elderly people with comorbidities, timely surgical treatment is the key to improve the efficacy of obturator hernia and prevent the deterioration of the condition. In addition, postoperative mortality is significantly associated with bowel resection and postoperative complications.

Additional file 3: Supplemental Table 3. Literature concerned the relationship between the length of proximal bowel resection and oncological outcomes in patients with colorectal cancer.

Additional file 1.

Additional file 1: Supplement Table 1. Cox regression analysis of prognostic factors for overall survival and disease-free survival in patients with IV stage rectal cancer.

This study aimed to explore the mechanism of lung metastases of colorectal cancer. The expression of CXCR4, CXCR7, and CXCL12 in colorectal cancer and lung metastases was analyzed by the immunohistochemical (IHC) method. Further, the study aimed at getting new insights into the role of CXCL12 in lung metastasis. A total of 41 patients who underwent surgical resections for both colorectal cancer and lung metastasis were retrospectively selected for this study. Also, 41 patients who underwent lung resection for benign lung disease were selected as the control group. In the in vivo experiment, the mice were injected with exosomes isolated from CT26. The mice with and without injection were sacrificed 3 weeks later. The lung tissue was analyzed by the IHC method and quantitative real-time PCR. The expression of CXCR7 and CXCL12 was significantly higher in lung metastases than in paired primary lesions. The expression of CXCL12 was significantly higher in the noncancerous lung tissue of patients with CRC than in patients with benign lung disease. Also, the expression of CXCL12 in the lung was higher in mice with exosome education. The results inferred that the expression of CXCR7 and CXCL12 was significantly higher in lung metastases than in primary tumors. Their combination could promote colorectal cancer lung metastasis. The expression of CXCL12 was elevated before metastasis. And this effect was induced by exosomes.

Malignant ascites-derived exosomes have been demonstrated to participate in tumor metastasis. In peritoneal metastasis, normal mesothelial cells (MCs) can be converted into carcinoma-associated fibroblasts (CAFs) by mesothelial-mesenchymal transition (MMT). Herein, we evaluated the effect of malignant ascites-derived exosomes on peritoneal MCs in vitro and in vivo experiments to determine whether exosomes could educate MCs and contribute to peritoneal metastasis. Under the treatment of ascites-derived exosomes, peritoneal MCs showed increased ability to proliferate and migrate. Expression of CAFs specific proteins markers in MCs, including fibroblast activation protein (FAP), alpha-smooth muscle actin (α-SMA), and fibronectin, were increased after treatment of exosomes. In clinical samples test, TGF-β1 was found to be overexpressed in both malignant ascites and malignant ascites-derived exosomes, and the high volume of TGF-β1 may be responsible for peritoneum fibrosis. In addition, exosomes can increase xenograft tumor growth by suppressing the inhibitive ability on tumor cells by MCs. Besides, CAFs specific proteins markers including FAP, α-SMA, and vimentin were increased in clinical peritoneal biopsies. The immunohistochemical staining for mice tumor biopsies also revealed increased expression of fibronectin and FAP, along with decreased expression of E-cadherin and VCAM-1 after exosomes treatment. Thus, malignant ascites-derived exosomes may be of importance in the development of peritoneal metastasis by facilitating MCs to proliferate and convert into CAFs by TGF-β1 induced MMT.

Colorectal cancer (CRC) is the fourth most common carcinoma with an increasing incidence in China [1]. In addition, comparing to solitary tumors, synchronous colorectal carcinoma (synchronous CRC) is a rare type of colorectal malignancy, which is defined as more than one primary colorectal carcinoma detected in one patient at the time of initial presentation [2]. The range of prevalence is 1.1%–8.1% of all colorectal cancers [3]. Synchronous CRC is often seen in males, and a previous large-scale study determined the male/female ratio as 1.85 [4]. The other known higher risk factors include inflammatory bowel diseases, Lynch syndrome, familial adenomatous polyposis, and adenomas/hyperplasic polyposis [5–8]. Moreover, the chromosomal instability, microsatellite instability (MSI), and gene methylation account for various predisposing lesions or factors for synchronous CRC [9]. Although synchronous CRC is identified as a significant entity at the clinical and molecular level, the clinical and pathological features and prognosis are yet controversial [5]. In addition, the results of previous studies which evaluated the prognostic significance of synchronous CRC are conflicting. Thus, the common consensus is reached on the occurrence of synchronous CRC as an independent predictive factor of survival as compared to solitary CRC after the operation [5,10,11]; the expected long-term survival rates of patients with synchronous CRC are yet controversial [12]. The present study aimed to compare the various clinicopathological features and short-term/long-term cancer-specific outcomes between synchronous and solitary CRC by a matched pair analysis with stratification based on age, sex, American Society of Anesthesiologists (ASA) class, BMI, cancer grade, tumor location, and tumor stage.

Background Cachexia has a devastating impact on survival and quality of life for many cancer patients and contributes to nearly one-third of all cancer deaths; also, it is associated with poor responses to chemotherapy and survival. A better understanding of the underlying mechanisms of cancer-associated cachexia (CAC), coupled with effective therapeutic approaches, will improve management of progressive functional impairment in cancer patients. Salidroside, a phenylpropanoid glycoside in Rhodiola rosea L, has been reported to possess potential anti-fatigue, anti-ageing, and anti-Alzheimer's disease properties. It is widely consumed as a nutritional supplement, but its effects on CAC and the possible mechanism remain a mystery. Methods In the murine models of cachexia induced by CT-26 and Lewis lung carcinoma (LLC) tumour, respectively, main features of CAC were determined after treatment of salidroside or chemotherapy. In vitro experiments were performed using murine C2C12 myotubes, which were treated by tumour necrosis factor-α. Levels of several critical muscle-related signal proteins such as mammalian target of rapamycin (mTOR), p-mTOR, and myosin heavy chain (MyHC) were examined using western blot both in vitro and in vivo. Results In the present study, we showed the exciting effect of salidroside on the treatment of CAC. In CT-26 and LLC models, respectively, salidroside treatment could effectively preserve the tumour-free body weight, decrease loss of adipose and gastrocnemius muscles, alleviate tumour burden, and prolong their survival time. Additionally, in combined chemotherapy, salidroside could synergistically enhance the anti-tumour activity of cisplatin, especially decreased or eliminated chemotherapy-induced cachexia. Further analysis demonstrated that salidroside could significantly increase expression of mTOR, p-mTOR, and MyHC in gastrocnemius muscle. Also, results in vitro showed that salidroside could not only obviously increase mTOR, p-mTOR, and MyHC expression in C2C12 myotubes but also effectively rescue their down-regulation induced by tumour necrosis factor-α. Conclusions In the current study, the exciting effect of salidroside on CAC suggested that salidroside supplementation might be a promising approach for a multi-targeted therapy for the treatment of CAC.

An increasing proportion of patients aged more than 70 years old are suffering from colorectal cancers. This study aimed to compare the short- and long-terms outcomes between open surgery (OS) or conventional laparoscopic surgery (LS) and hand-assisted laparoscopic surgery (HALS) in treatment of these elderly patients with right colon cancers. We retrospectively reviewed patients who underwent right colon resections for cancers in our institution between June, 2009 and December, 2014. Short- and long-terms outcomes including surgical endpoints, postsurgical recovery data, postoperative morbidity and mortality, overall survival and disease-free survival were compared among OS, LS, and HALS groups. All data were analyzed by SPSS 22.0. Finally, 69 consecutive patients (OS = 26, LS = 24, HALS = 19) with right colon cancers were included in the analysis. Compared with OS, HALS was associated with less time to first anus exhaust (P = .013), first liquid diet (P = .045), and first soft diet (P = .036). Meanwhile, there were significant less operative time (P = .0027), blood loss (P

Isoliquiritigenin (ISL) is an important flavonoid component of licorice and has been reported to possess anti-inflammatory and antioxidant properties, but its exact mechanism of action remains poorly understood. Previously, we demonstrated that ISL could suppress IL-6 expression in multiple myeloma. Here, we further characterized the anti-inflammatory effects of ISL in several psoriasis models, including the keratin 14/vascular endothelial growth factor (VEGF) transgenic mouse, the imiquimod (IMQ)-induced psoriasis-like mouse, and the human keratinocytes HaCaT and NHEK in vitro. We found that ISL ameliorated the inflammatory process in psoriasis models but not in their respective controls. Moreover, the anti-inflammatory effects of ISL were attributed to the suppression of nuclear factor-κB (NF-κB) activity, which consequently resulted in the reduction of pro-inflammation cytokines IL-6 and IL-8 expression. In conclusion, ISL exhibited anti-inflammatory effects in psoriasis models, by downregulating IL-6 and IL-8 via suppression of NF-κB activity, suggesting that ISL might serve as a potential candidate for treatment of psoriasis and other autoimmune inflammatory diseases.ISL could ameliorate the inflammatory process of psoriasis. ISL could suppress NF-κB and subsequent production of a series of pro-inflammatory cytokines. Dual-inhibitory activity against IL-6 and IL-8 of ISL is implemented via inhibiting NF-κB. ISL exerts no inhibitory effects on normal human keratinocytes or wild-type Balb/c mice, implying its low toxicity and safety.

Background Although conventional laparoscopic and hand-assisted laparoscopic surgery for colorectal cancer is widely used today, there remain many technical challenges especially for right colon cancer in obese patients. Herein, we develop a novel hand-assisted laparoscopic surgery (HALS) with complete mesocolic excision (CME), D3 lymphadenectomy, and a total “no-touch” isolation technique (HALS-CME) in right hemicolectomy to overcome these issues. According to previous clinic practice, this novel procedure is not only feasible and safe but has several technical merits. However, the feasibility, short-term minimally invasive virtues, long-term oncological superiority, and potential total “no-touch” isolation technique benefits of HALS-CME should be confirmed by a prospective randomized controlled trial. Methods/design This is a single-center, open-label, noninferiority, randomized controlled trial. Eligible participants will be randomly assigned to the HALS-CME group or to the laparoscopic surgery with CME, D3 lymphadenectomy, and total “no-touch” isolation technique (LAP-CME) group, or to conventional laparoscopic surgery with CME and D3 lymphadenectomy (cLAP) group at a 1:1:1 ratio using a centralized randomization list. Primary endpoints include safety, efficacy, and being oncologically clear, and 3-year disease-free, progression-free, and overall survival. Second endpoints include operative outcomes (operation time, blood loss, and incision length), pathologic evaluation (grading the plane of surgery, length of proximal and distal resection margins, distance between the tumor and the central arterial high tie, distance between the nearest bowel wall and the same high tie, area of mesentery resected, width of the chain of lymph-adipose tissue, length of the central lymph-adipose chain, number of harvested lymph nodes), and postoperative outcomes (pain intensity, postoperative inflammatory and immune responses, postoperative recovery). Discussion This trial will provide valuable clinical evidence for the feasibility, safety, and potential total “no-touch” isolation technique benefits of HALS-CME for right hemicolectomy. The hypothesis is that HALS-CME is feasible for the radical D3 resection of right colon cancer and offers short-term safety and long-term oncological superiority compared with conventional laparoscopic surgery. Trial registration ClinicalTrials.gov, NCT02625272. Registered on 8 December 2015. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2084-3) contains supplementary material, which is available to authorized users.

SPIRIT 2013 Checklist: Recommended items to address in a clinical trial protocol and related documents. (DOC 116 kb)

Background It remains unclear whether or not preservation of the left colic artery (LCA) for colorectal cancer surgery. The objective of this updated systematic review and meta-analysis is to evaluate the current scientific evidence of LCA non-preservation versus LCA preservation in colorectal cancer surgery. Methods A systematic search was conducted in the Medline, Embase, PubMed, Cochrane Library, ClinicalTrials, Web of Science, China National Knowledge Infrastructure and Chinese BioMedical Literature Database, and reference without limits. Quality of studies was evaluated by using the Newcastle-Ottawa scale and the Cochrane Collaboration's tool for assessing the risk of bias. Effective sizes were pooled under a random- or fixed-effects model. The funnel plot was used to assess the publication bias. The outcomes of interest were oncologic consideration including the number of apical lymph nodes, overall recurrence, 5-years overall survival, and 5-years disease-free survival (DFS); safety consideration including overall 30-day postoperative morbidity and overall 30-day postoperative mortality; anatomic consideration including anastomotic circulation, anastomotic leakage, urogenital, and defaecatory dysfunction. Results Twenty-four studies including 4 randomized controlled trials (RCTs) and 20 cohort studies with a total of 8456 patients (4058 patients underwent LCA non-preservation surgery vs 4398 patients underwent LCA preservation surgery) were enrolled in this meta-analysis. The preservation of LCA was associated with significantly less anastomotic leakage (odds ratio 1.23, 95% confidence interval 1.02-1.48, P = .03). In term of sexual dysfunction, urinary retention, the number of apical lymph nodes, and long-term oncologic outcomes, there were no significant differences between the LCA non-preservation and LCA preservation group. It was hard to draw definitive conclusions on other outcomes including operation time, blood loss, the first postoperative exhaust time, and perioperative morbidity and mortality for insufficient data and highly significant heterogeneity among studies. Conclusions The pooled data provided evidence to support the LCA preservation preferred over LCA non-preservation in anastomotic leakage. Future more large-volume, well-designed RCTs with extensive follow-up are needed to draw a definitive conclusion on this dilemma.

Study results on the association between RAD51 gene -135G/C polymorphism and risk of myelodysplastic syndrome (MDS) or acute leukemia are inconsistent. A meta-analysis was conducted to identify the association. A systematic search was performed in PubMed, Embase, CNKI, VIP, Wanfang databases to collect all relevant studies until January 2013. Meta-analysis was carried out using fixed/random model by Review Manager 5.1 and STATA10.0. A total of 10 eligible studies with 2,656 patients and 3,725 controls were included in meta-analysis. Significant association was detected between -135G/C polymorphism and increased MDS risk (CC + GC vs. GG: OR = 1.46, 95% CI = 1.11-1.92; CC vs. GC + GG: OR = 2.45, 95% CI = 1.23-4.89), while no association was observed for acute leukemia. Subgroup analysis by subtypes of acute leukemia and ethnicity showed no significant results either. Our meta-analysis indicated that the -135G/C polymorphism might be associated with increased susceptibility of MDS. However, lack of evidence supported association of this polymorphism with acute leukemia. Additional well-designed studies with larger samples are required to verify our results.

Lateral lymph node (LLN) metastasis is a major cause of local recurrence of advanced rectal cancer. Although there is much controversy between Western and Eastern countries on whether lateral pelvic lymph node dissection (LLND) or neoadjuvant chemo-radiation (nCRT) is preferable for the treatment of LLN metastases, existing retrospective cohorts mainly focus on all middle/low advanced rectal cancer patients, not the specific individuals with suspicion of LLN metastases. The aim of this trial is to assess the efficacy and safety of LLND for rectal cancer patients with suspicion of LLN metastases. This prospective, multicenter, randomized controlled, single-blinded, phase III trial is designed to enroll 512 eligible patients with advanced rectal cancer and preoperative enlarged lateral lymph nodes. The population will be randomly assigned into the solely total mesorectal excision (TME) group or the TME + LLND group after eligible selection. The primary outcomes are to be 3-year local recurrence rate and 3-year disease-free survival, and the secondary outcomes include 3-year overall survival, 1-year sexual and urinary function, and perioperative outcomes. This is the first randomized trial to investigate the efficacy and safety of LLND for advanced low rectal cancer patients with suspicion of LLN metastases; the result is expected to provide new evidence for the treatment of LLN where there is suspicion of metastases in advanced rectal cancer patients. This trial was registered at ClinicalTrials.gov (identifier NCT02614157 ) Registered on 24 November 2015.

Single-nucleotide polymorphisms located in the microRNA biogenesis pathway could alter the risk for developing prostate cancer. The present study was intended to identify common genetic variants responsible for prostate cancer susceptibility in the GEMIN4 gene. The high-resolution melting method was used to genotype seven polymorphisms (rs7813, rs4968104, rs3744741, rs2740348, rs1062923, rs910925, and rs910924) in the GEMIN4 gene in 300 prostate cancer patients and 244 matched controls. The encouraging discovery in this study was in the rs2740348. Patients carrying the variant heterozygote GC genotype in the rs2740348 were at a 36% decreased risk of prostate cancer (odds ratio [OR] = 0.64; 95% confidence interval [CI] = 0.42, 0.99). Similarly, this variant allele carrier showed significant risk for prostate cancer (OR = 0.64). In addition, subjects carrying the homozygote TT genotype in the rs7813 had a significantly increased risk of prostate cancer (OR = 2.53, 95% CI = 1.07, 6.28). Two common haplotypes were found to be associated with decreased risk of prostate cancer. In the subgroup analysis, higher risk of more severity of prostate cancer (clinical stage III and IV) was observed in individuals with the rs7813 TT genotype (OR = 2.64, 95% CI = 1.02, 7.64), while lower risk of more severity of prostate cancer was observed in individuals with the rs3744741 T allele (OR = 0.69, 95% CI = 0.50, 0.96). Overall, our study provides substantial support for the association between the GEMIN4 gene and the risk of prostate cancer.

Background Over half of the patients were diagnosed with colorectal cancer after 70 years of age. The choice of the most suitable chemotherapy strategy is the major challenge for elderly patients. Previous trials indicated that elderly patients with stage II/III colorectal cancer obtained no significant benefits from oxaliplatin-based adjuvant chemotherapy. Therefore, single-agent oral capecitabine is regarded as an effective alternative with retained efficacy and improved flexibility. However, the optimal dose of capecitabine for elderly patients remains controversial. Recent studies have adopted a low-dose strategy (1,000 mg/m2) for elderly patients, but the long-term efficacy of this strategy has not been identified so far. Thus, we designed this trial to investigate non-inferiority of the lower-dose strategy of capecitabine compared with the approved-dose strategy for adjuvant chemotherapy of elderly patients with stage II/III colorectal cancer. Methods LC-ACEC (Low-dose Capecitabine Adjuvant Chemotherapy for Elderly Patients With Stage II/III Colorectal Cancer) is a prospective, randomized, open-label, non-inferiority phase III clinical trial including 926 eligible patients. Patients will be randomly assigned to receive a capecitabine adjuvant chemotherapy strategy of lower dose (1,000 mg/m2 twice daily on days 1 to 14 of every 21 days) or approved dose (1,250 mg/m2 twice daily on days 1 to 14 of every 21 days). The primary outcome is 3-year disease-free survival. Secondary outcomes include 3-year overall survival, toxic and side effects during treatment, completion rate, and quality of life. Discussion This is the first randomized trial to evaluate the efficacy and safety of a low-dose strategy of capecitabine in adjuvant chemotherapy of elderly patients with stage II/III colorectal cancer, and the results are believed to provide new evidence on the treatment of elderly patients with colorectal cancer. Trial registration ClinicalTrials.gov identifier NCT02316535 (Dec. 12, 2014).