Comparative study of oncologic efficacy of cephalomedial to lateral dissection versus medial to lateral dissection in laparoscopic total mesorectal excision for rectal cancer: An RCT study.

BACKGROUND AND OBJECTIVES: We compared the 3-year overall survival between cephalomedial-to-lateral approach proctectomy (CEMP) and medial-to-lateral approach proctectomy (MAP) in patients undergoing laparoscopic total mesorectal excision for rectal cancer. The advantages of CEMP and the clinical value of No. 253 lymph nodes resection have not been objectively analyzed in literature. METHODS: This was a prospective, two-arm, multicenter, single-blinded, randomized trial. The primary endpoint was 3-year overall survival, and secondary endpoints included safety, feasibility, oncological radicality (including number of No. 253 lymph nodes harvested), short-term outcome, 3-year disease-free survival, rate of postoperative complications, mortality, and rate of recurrence. RESULTS: From May 2016 to July 2020, 506 patients were enrolled-256 in the CEMP group and 250 in the MAP group. Comparison of overall survival and disease-free survival showed that there was treatment benefit in the CEMP group (28.22 ± 12.12 vs. 27.44 ± 13.06, p = 0.485; 27.24 ± 12.01 vs. 26.42 ± 12.81; p = 0.457). More No. 253 lymph nodes were harvested in the CEMP group, and cases with positive No. 253 lymph nodes had worse prognosis in stage III. Surgical safety was equal for both approaches. CONCLUSIONS: Dissection of No. 253 lymph nodes may be important to improve clinical prognosis, but further studies with larger samples are needed to confirm this finding.

Rab27A promotes cellular apoptosis and ROS production by regulating the miRNA-124-3p/STAT3/RelA signalling pathway in ulcerative colitis.

Ulcerative colitis (UC) is a multifactorial inflammatory disease, and increasing evidence has demonstrated that the mechanism of UC pathogenesis is associated with excessive cellular apoptosis and reactive oxygen species (ROS) production. However, their function and molecular mechanisms related to UC remain unknown. In this study, Rab27A mRNA and protein were proven to be overexpressed in intestinal epithelial cells of UC patients and DSS-induced colitis mice, compared with control (P < 0.05). And Rab27A silencing inhibits inflammatory process in DSS-induced colitis mice (P < 0.05). Then, it was shown that knockdown of Rab27A suppressed apoptosis and ROS production through modulation of miR-124-3p, whereas overexpression of Rab27A promoted apoptosis and ROS production in LPS-induced colonic cells. In addition, enhanced expression of miR-124-3p attenuated apoptosis and ROS production by targeting regulation of STAT3 in LPS-induced colonic cells. Mechanistically, we found Rab27A reduced the expression and activity of miR-124-3p to activate STAT3/RelA signalling pathway and promote apoptosis and ROS production in LPS-induced colonic cells, whereas overexpression of miR-124-3p abrogated these effects of Rab27A. More importantly, animal experiments illustrated that ectopic expression of Rab27A promoted the inflammatory process, whereas overexpression of miR-124-3p might interfere with the inflammatory effect in DSS-induced colitis mice. In summary, Rab27A might modulate the miR-124-3p/STAT3/RelA axis to promote apoptosis and ROS production in inflammatory colonic cells, suggesting that Rab27A as a novel therapeutic target for the prevention and treatment of UC patients.

Increased epoxyeicosatrienoic acids may be part of a protective mechanism in human ulcerative colitis, with increased CYP2J2 and reduced soluble epoxide hydrolase expression.

BACKGROUND: Previous preclinical evidence has suggested that the elevation of epoxyeicosatrienoic acids (EETs) derived from the cytochrome P450 (CYP) epoxygenases-dependent metabolism of arachidonic acid has important anti-inflammatory effects. However, the levels of EETs and their synthetic and metabolic enzymes in human ulcerative colitis has not been evaluated. METHOD: To evaluate EETs and the expression of relevant CYP isoforms and the metabolizing enzyme, soluble epoxide hydrolase (sEH), tissue biopsies were collected from 16 pairs of ulcerative colitis patients' tissues and matched with adjacent non-inflamed tissues. EETs were extracted from tissue homogenates and analyzed by liquid chromatography coupled with tandem mass spectrometry. RESULTS: The concentration of EETs was higher in ulcerative colitis tissues compared with matched adjacent non-inflamed tissues (1.91 ±â€¯0.98 ng/mg vs. 0.96 ±â€¯0.77 ng/mg, mean ±â€¯SD, P < 0.01). As shown by immunohistochemistry, sEH was present in the cytoplasm and intestinal mucosa and showed a decline in ulcerative colitis tissues compared with matched adjacent non-inflamed tissues. Western blot analyses showed reduced sEH expression in ulcerative colitis tissues compared with matched adjacent non-inflamed tissues, whereas CYP2J2 increased in ulcerative colitis tissues (P < 0.05). However, there was no statistically significant difference observed in CYP2C8 and CYP2C9 protein expression between them (P > 0.05). CONCLUSION: Our data suggest that the increase in EET levels may be part of a protective mechanism in ulcerative colitis. Furthermore, the concentration of EETs could be a key factor for drug therapy for ulcerative colitis.

Lymphadenectomy Around Inferior Mesenteric Artery in Low-Tie vs High-Tie Laparoscopic Anterior Resection: Short- and Long-Term Outcome of a Cohort of 614 Rectal Cancers.

BACKGROUND: Preservation of the left colic artery in low-tie (LT) of inferior mesenteric artery remains controversial compared to high-tie (HT) in the colon and rectal cancers, for lymph node dissection, anastomotic leakage, and oncological outcome. This cohort study aims to analyze short- and long-term outcomes of laparoscopic anterior resections in LT vs HT for rectal cancers. METHODS: We analyzed a cohort of laparoscopic AR for RC from 2013 to 2016 at Renji Hospital, Shanghai, China. Short- and long-term outcome in LT vs HT group were compared for clinico-demographic characteristics, operative-time, lymph node dissection, short-term 30-day outcome, and long-term 3- and 5-year overall survival as well as disease-free survival. The x2, t-test, and logistic regressions analysis were used and p<0.05 was considered significant. RESULTS: The cohort consisted of 614 laparoscopic AR with LT (236) and HT (378). The clinicodemographic characteristics were comparable among the groups. The surgery took longer in LT. The yield of LND was similar. Leakage occurred in 12.21% (n=75). Leakage was fewer in LT than HT, 8.89% vs 14.28%, p=0.047. The postoperative severe complications were higher in HT. The 30-day mortality was nil. The long-term 3- and 5-year overall survival and disease-free survival were similar in LT and HT. CONCLUSION: The LT with preservation of left colic artery had similar lymph node yield, but lower leakage and complications than HT in laparoscopic anterior resections for rectal cancers. The long-term 3- and 5-year overall and disease-free survival were similar in the two groups.

Volume-based histogram analysis of dynamic contrast-enhanced MRI for estimation of gliomas IDH1 mutation status.

PURPOSE: The study aimed to investigate whether isocitrate dehydrogenase 1 (IDH1) mutation status in gliomas can be estimated by volume-based histogram analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). MATERIALS AND METHODS: Preoperative DCE-MRI data of 85 pathologically confirmed glioma patients including 33 carrying IDH1 mutant type (IDH1mut) and 52 with IDH1 wildtype (IDH1wt) were reviewed in a retrospective approach. Regions of interest (ROI) covering entire tumor volume were manually delineated using O.K. software (OmniKinetics, GE Healthcare, China). Histogram parameters of volume transfer constant (Ktrans) and volume of extravascular /extracellular space per unit volume of tissue (Ve) derived from DCE-MRI were obtained. Mann-Whitney U tests were made to compare the differences in histogram parameters of Ktrans and Ve between IDH1mut and IDH1wt in all gliomas and high-grade gliomas (HGGs, grade III and IV). Receiver operator characteristic (ROC) analysis were implemented to assess the diagnostic performance. RESULTS: In histogram parameters of Ktrans and Ve, pairwise comparisons demonstrated statistically significant differences in mean, standard deviation (SD), 90th and 95th percentiles (90%, 95%) values between IDH1mut and IDH1wt in all cases of gliomas and HGGs (P < 0.05, respectively). The ROC analysis revealed that the cut-off values of 95% value of Ktrans (0.097 min-1) and mean value of Ve (0.099) provided the best combination of sensitivity and specificity to distinguish all gliomas with IDH1mut from IDH1wt. In HGGs, the cut-off values of mean value of Ktrans and Ve (0.044 min-1, 0.099) played similar role. CONCLUSION: Volume-based histogram analysis of DCE-MRI performs well in identification of IDH1mut gliomas.

Long non-coding RNA NEAT1 promotes colorectal cancer progression by competitively binding miR-34a with SIRT1 and enhancing the Wnt/ß-catenin signaling pathway.

In recent years, accumulating evidence has indicated that long non-coding RNAs (lncRNAs) are powerful factors influencing the progression of multiple malignancies. Although a relationship between the lncRNA NEAT1 (nuclear enriched abundant transcript 1) and colorectal cancer has previously been reported, the functional mechanism underlying the involvement of NEAT1 in colorectal cancer remains unknown. In this study, we report that NEAT1 expression is up-regulated in colorectal cancer tissues, which correlates with advanced clinical features, poor overall survival and disease free survival. Up-regulated NEAT1 promotes cell proliferation and metastasis of colorectal cancer both in vitro and in vivo. Moreover, NEAT1 functions as an oncogene influencing cell viability and invasion in part by serving as a competing endogenous RNA (ceRNAs) modulating miRNA-34a expression, leading to subsequent repression of the miR-34a/SIRT1 axis and activation of the Wnt/ß-catenin signaling pathway. Taken together, our study demonstrates that the lncRNA NEAT1 may serve as a prognostic biomarker and a potential therapeutic target in colorectal cancer.

Monopolar Electrosurgical Scissors Versus Harmonic Scalpel in Robotic Anterior Resection of Rectal Cancer: A Retrospective Cohort Study.

Background: Robot-assisted surgical techniques have been introduced in recent years as an alternative minimally invasive approach for colorectal surgery. In practice, we found that the monopolar electrosurgical scissors had its unique advantages in preservation of the pelvic autonomic nerves. We performed a retrospective review of short-term results between using monopolar electrosurgical scissors and harmonic scalpel in robotic anterior resection (using the da Vinci® Surgical System) in rectal cancer patients. Method: Forty-six patients who underwent robotic anterior resection of rectal cancer from June 2016 to January 2018 were retrospectively analyzed and compared. Twenty-two cases underwent resection using monopolar electrosurgical scissors and 24 cases underwent resection using the harmonic scalpel. Patient characteristics, perioperative clinical results, complications, and pathological results were compared between two groups. Results: There were not significantly different patient characteristics between the two groups. The mean operative time was lesser in the monopolar electrosurgical scissors group than in the inharmonic scalpel group [95.59 ± 21.44 minutes versus 81.45 ± 13.89 minutes, P < .01]. The mean estimated blood loss was lesser in the monopolar electrosurgical scissors group than in the inharmonic scalpel group [48.64 ± 19.35 mL versus 61.82 ± 24.23 mL, P = .03]. The complication rate was 18.2% in the monopolar electrosurgical scissors group and 16.7% in the harmonic scalpel group (P = .89). The mean time of postoperational urinary catheter was lesser in the monopolar electrosurgical scissors group [3.73 ± 1.16 days versus 4.59 ± 1.71 days, P = .02]. The day to first passing flatus [3.45 ± 0.80 days versus 3.59 ± 1.14 days, P = .67], feeding time [4.50 ± 1.00 days versus 4.05 ± 1.87 days, P = .35], hospital stay [8.18 ± 3.74 days versus 8.68 ± 3.44 days, P = .52], and the mean number of harvested lymph nodes of detection [13.59 ± 1.71 versus 13.77 ± 1.41, P = .67] were comparable between procedures. Conclusion: Monopolar electrosurgical scissors were used safely and effectively in robotic anterior resection of rectal cancer (using the da Vinci Surgical System). The use of monopolar electrosurgical scissors has benefits in performing blunt and sharp separation in narrow pelvic and cheaper hospitalization expenses.

Expression of CHD5 may serve as an independent biomarker of prognosis in colorectal cancer via immunohistochemical staining.

Chromodomain helicase DNA binding protein 5 (CHD5) acts as a tumor suppressor in various types of cancer and belongs to CHD protein family. However, no prognostic role for CHD5 has yet been indicated in colorectal cancer. Therefore, the aim of this study was to investigate a possible association between CHD5 expression and colorectal cancer prognosis. Furthermore, immunochemistry was used to investigate CHD5 expression in 310 CRC tissue specimens. Expression of CHD5 significantly positively correlated with the lymphatic metastasis (P=0.007). The prognostic value of CHD5 in relation to overall survival was analyzed by Kaplan-Meier analysis and Cox proportional hazard models. The mean and medium follow-up times after surgery were 5.5 and 6.6 years, respectively. A total of 150 patients died during the 13 years of follow-up in the survey period. We also demonstrated that overall survival was poor in CRC patients with low expression of CHD5 (P=0.003). Accordingly, multivariate analysis identified low CHD5 expression as an independent risk factor (P=0.014), especially in elderly patients or those with late stage cancers. We suggest that CHD5 could serve as an independent prognostic biomarker for colorectal patients. This finding also should be verified by other research groups.

Plastic wound protectors decreased surgical site infections following laparoscopic-assisted colectomy for colorectal cancer: A retrospective cohort study.

Laparoscopic surgery is widespread and safe for the management of patients with colorectal cancer (CRC). Although the use of standard surgical techniques can prevent perioperative wound infections, surgical site infections (SSIs) remain an unresolved complication in laparoscopic-assisted colectomy. The present study investigated the ability of plastic wound protectors applied to the extraction incision during the externalized portion of the procedure to reduce the rate of infection in laparoscopic-assisted colectomy. We completed a retrospective review of the medical records of patients who underwent nonemergent laparoscopic-assisted between January 2015 and June 2016. Outcomes for patients with and without the use of a wound protector were compared. A total of 109 patients were included in this study. There was 1 patient in the wound protector group (n = 57) and 7 in the nonwound protector group (n = 52) who developed a wound infection at the colon extraction site (P = .02). Furthermore, the average postoperative hospital stay in the wound protector group was shorter compared to the nonwound protector group (7.47 ±â€Š0.24 vs 8.73 ±â€Š0.54 days, P = .03). In conclusion, this study indicates that the use of a plastic wound protector during laparoscope-assisted colectomy does reduce postoperative wound infection rates, and the wound protectors are beneficial for specimen extraction and digestive tract reconstruction.

TEAD1 enhances proliferation via activating SP1 in colorectal cancer.

Colorectal cancer (CRC) is the most common type of gastrointestinal cancer. However, up to date, the specific mechanism for CRC proliferation remains unclear. Transcriptional enhancer activator domain 1 (TEAD1) is a transcription factor belongs to the TEAD family, which plays an important role in cancers progression. Here, we investigated the role of TEAD1 in CRC, and found that overexpression of TEAD1 was proved to increase colorectal cancer cells proliferation, whereas, knockdown of TEAD1 reduces the growth of cancer cells by BrdU assay, cell cycle analysis and MTT assay. Furthermore, we performed luciferase assay and chromatin immunoprecipitation assay to investigate the underlying mechanism of TEAD1 in CRC system, and observed that TEAD1 could enhance the expression levels of SP1, by directly binding to its promoter. In summary, we provided evidence for a novel mechanism regulating growth and proliferation in colorectal cancer.

The clinical impact of ICOS signal in colorectal cancer patients.

The inducible T-cell co-stimulator (ICOS) belongs to the B7-CD28 immunoglobulin superfamily, which is currently the subject of intense study due to great successes gained in treatment of different malignancies by disrupting their family members. However, the role of ICOS played in colorectal cancer (CRC) remains poorly understood. A tissue microarray (n = 310) was stained with the ICOS specific antibody and ICOS expression is decreased in patients with either lymphatic or distant metastasis and inversely associated with CEA level and TNM stage of CRC patients. Importantly, high ICOS expression is significantly correlated with overall survival (OS) of CRC patients (n = 230, p < 0.001), and ICOS expression is also proved to be an independent prognostic factor by multivariate analysis. Surgical excised CRC specimens (n = 26) were enzymatically digested to get the tumor-infiltrating leukocytes and ICOS is mainly expressed on CD4(+) T cells and its ligand ICOSL is detected on macrophages and tumor cells. ICOS expression level is associated with increased cytotoxic T lymphocyte antigen (CTLA)-4 (p < 0.001) and programmed death (PD-1) (p = 0.005) expression on T cells and more infiltrated CD8(+) T cells (p < 0.001). Interestingly, ICOS(+)CD4(+) cells isolated from tumor tissues have high T-bet and interferon (IFN)γ expression, the characteristics of Th1 cells, compared to ICOS(-)CD4(+) cells. In addition, the correlation between the percentage of ICOS(+)CD4(+) T cells in tumor tissue and peripheral blood was detected. Conclusively, expression of ICOS is associated with improved survival in CRC and percentage of ICOS(+)CD4(+) cells acting as Th1 cells in either primary tumor tissue or peripheral blood may be a clinical biomarker for good prognosis of CRC patients.

High expression of Rab3D predicts poor prognosis and associates with tumor progression in colorectal cancer.

Rab3D belongs to Rab protein family. Previous reports showed that the expression of Rab3D was dysregulated in various types of cancer. Rab3D belongsRab3D belongs. However, little is known about the role of Rab3D in carcinogenesis and progression of colorectal cancer (CRC). Here, we first evaluated the expression of Rab3D in 32 fresh CRC and matched normal tissues and found Rab3D was dramatically increased in CRC tissues compared to normal tissues (p<0.001). Furthermore, immunochemistry was used to investigate Rab3D expression in 300CRC tissue specimens. The expression of Rab3D significantly positively correlated with the tumor size (p=0.041), CEA level (p=0.007), tumor classification (p=0.030), lymphatic metastasis (p<0.001), distant metastasis (p=0.013) and clinical stage (p=0.003). We also demonstrated that overall survival is poor in CRC patients with high expression of Rab3D (p<0.001). Finally, we showed that Rab3D activated Akt/GSK3ß/Snail pathway and induced EMT process in colorectal cancer cells. In conclusion, this study establishes increased Rab3D expression is associated with invasiveness of CRC cells, and Rab3D expression status may serve as a reliable prognostic biomarker in CRC patients.

MicroRNA-187 inhibits tumor growth and invasion by directly targeting CD276 in colorectal cancer.

Aberrantly expressed microRNAs contribute to the initiation and progression of human cancers. However, the underlying functions of microRNA-187 (miR-187) in colorectal cancer (CRC) remain largely unexplored. Here, we demonstrated that miR-187 was significantly down-regulated in CRC tissues and cell lines compared to their normal counterparts. By Kaplan-Meier analysis, we revealed that decreased miR-187 expression was closely associated with shorter overall survival and relapse-free survival of patients with CRC. By gain- and loss-of-function studies, we showed that miR-187 remarkably suppressed CRC cell proliferation, migration, invasion, and promoted cell apoptosis. Furthermore, bioinformatics analysis and luciferase reporter assay identified that CD276 was the direct functional target of miR-187 in CRC. Genetic silencing of CD276 recapitulated similar phenotype as observed in over-expression of miR-187, and restoration of CD276 completely rescued the inhibitory effect of miR-187 in CRC cells. Taken together, our study implied the essential roles of miR-187 in suppressing CRC progression, and a novel link between miR-187 and CD276 in CRC.

Increased expression of Rab5A predicts metastasis and poor prognosis in colorectal cancer patients.

Rab5A is reported to correlate with cancer development and progression. The purpose of this study is to explore the association between Rab5A expression and the clinical characteristics of colorectal cancer (CRC). Data containing three independent investigations from Oncomine database demonstrated that Rab5A is overexpression in CRC compared with normal tissue, similar result was also found in 32 matched CRC tissue samples by qPCR. The protein expression of Rab5A was examined in 390 CRC specimens and the results showed that high expression of Rab5A was significantly correlated with tumor size (P = 0.008), serum CEA (P = 0.002), liver metastasis (P = 0.014) and clinical stage (P = 0.010). Kaplan-Meier method suggested that overexpression of Rab5A protein expression had shorter overall survival times in CRC patients (P < 0.001). Multivariate Cox regression analysis confirmed Rab5A expression, tumor size and clinical stage as independent prognostic factor in CRC. In conclusion, the data indicated that higher expression of Rab5A was observed in CRC tissues and Rab5A may be identified as a useful predictor of metastasis and prognosis for CRC.

ATAD2 Overexpression Identifies Colorectal Cancer Patients with Poor Prognosis and Drives Proliferation of Cancer Cells.

ATPase family AAA domain-containing 2 (ATAD2) has been identified as a critical modulator involved in cell proliferation and invasion. The purpose of this study was to explore the expression of ATAD2 in CRC tissues as well as its relationship with degree of malignancy. Data containing three independent investigations from Oncomine database demonstrated that ATAD2 is overexpressed in CRC compared with normal tissue, and similar result was also found in 32 pairs of CRC tissues by qPCR. The protein expression of ATAD2 was examined in six CRC cell lines and 300 CRC specimens. The results showed that high expression of ATAD2 was significantly correlated with tumor size (P < 0.001), serum CEA (P = 0.012), lymph node metastasis (P = 0.018), liver metastasis (P = 0.025), and clinical stage (P = 0.004). Kaplan-Meier method suggested that higher ATAD2 protein expression significantly associated with the overall survival (OS) of CRC patients (P < 0.001) and was an independent predictor of poor OS. Functional studies showed that suppression of ATAD2 expression with siRNA could significantly inhibit the growth in SW480 and HCT116 cells. These results indicated that ATAD2 could serve as a prognostic marker and a therapeutic target for CRC.

Up-regulated CKS2 promotes tumor progression and predicts a poor prognosis in human colorectal cancer.

Cyclin-dependent kinases regulatory subunit 2 (CKS2) is a cyclin-dependent kinase-interacting protein, which is essential for cell cycle regulation. Elevated expression of CKS2 has been demonstrated in multiple types of human malignancies. However, the clinical significance, oncogenic functions and related mechanisms of CKS2 in colorectal cancer (CRC) remain largely unexplored. In this study, data from Oncomine database revealed that CKS2 is significantly up-regulated in CRC tissues compared with their normal counterparts. Immunohistochemical analysis of a CRC tissue microarray demonstrated that elevated CKS2 expression is closely associated with enhanced TNM stage, larger tumor size and a poor prognosis in patients with CRC. Multivariate Cox regression analysis revealed that CKS2 and TNM stage are two independent prognostic factors for CRC. Suppression of CKS2 expression resulted in decreased cell viability, increased cell apoptosis, cell cycle arrest and reduced expression of cyclins in Caco-2 and SW620 cells. Furthermore, gain and loss of function studies demonstrated that CKS2 promotes cell invasion in CRC cells through regulating claudin1. Taken together, our study reveal that CKS2 is promising prognostic indicator and contributes to tumor progression in CRC, and support that CKS2-related signaling may represent a novel target for CRC therapy.

Prognostic value of regulator of G-protein signaling 6 in colorectal cancer.

Reprogrammed metabolism is a hallmark of cancer cells. Regulator of G-protein signaling 6 (RGS6), which is frequently down-regulated in multiple human malignancies, has been demonstrated to play a critical function in energy metabolism, cell apoptosis and tumorigenesis. However, limited knowledge is known about the expression pattern and prognostic value of RGS6 in colorectal cancer (CRC). In this study, we first observed that RGS6 mRNA and protein is commonly downregulated in 32 paired CRC tissues compared with their normal counterparts. Furthermore, by a large scale of immunohistochemical analysis in a tissue microarray containing 310 cases of CRC specimens, we demonstrated that the protein expression of RGS6 expression is downregulated in 40.97% (127/310) samples and detected that decreasing RGS6 expression is closely correlated with enhanced tumor size, CEA level, T classification, TNM stage, and easier lymphatic and distant metastasis. Meanwhile, Kaplan-Meier survival analysis showed that CRC patients with a lower RGS6 expression have a poorer clinical outcome than those with a higher RGS6 expression. Multivariate Cox regression analysis revealed that RGS6, lymphatic metastasis and distant metastasis are the independent prognostic factors for overall survival rate of CRC patients. Taken together, our studies reveal the prognostic value of RGS6 in CRC and support that RGS6 may act as a molecular target for CRC treatment.

Systematic review of anastomotic leakage rate according to an international grading system following anterior resection for rectal cancer.

BACKGROUND: A generally acceptable definition and a severity grading system for anastomotic leakages (ALs) following rectal resection were not available until 2010, when the International Study Group of Rectal Cancer (ISGRC) proposed a definition and a grading system for AL. METHODS: A search for published data was performed using the MEDLINE database (2000 to December 5, 2012) to perform a systematic review of the studies that described AL, grade AL according to the grading system, pool data, and determine the average rate of AL for each grade after anterior resection (AR) for rectal cancer. RESULTS: A total of 930 abstracts were retrieved; 40 articles on AR, 25 articles on low AR (LAR), and 5 articles on ultralow AR (ULAR) were included in the review and analysis. The pooled overall AL rate of AR was 8.58% (2,085/24,288); the rate of the asymptomatic leakage (Grade A) was 2.57%, that of AL that required active intervention without relaparotomy (Grade B) was 2.37%, and that of AL that required relaparotomy (Grade C) was 5.40%. The pooled rate of AL that required relaparotomy was higher in AR (5.40%) than in LAR (4.70%) and in ULAR (1.81%), which could be attributed to the higher rate of protective defunctioning stoma in LAR (40.72%) and ULAR (63.44%) compared with that in AR (30.11%). CONCLUSIONS: The new grading system is simple that the ALs of each grade can be easily extracted from past publications, therefore likely to be accepted and applied in future studies.