Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Objective:The aim of this study was to evaluate the safety and efficacy of elective rectal resection for rectal cancer in adults by robotic surgery compared with conventional laparoscopic surgery.Summary of Background Data:Technological advantages of robotic surgery favor precise dissection in narro

Robotic Versus Laparoscopic Minimally Invasive Surgery for Rectal Cancer: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Robotic versus laparoscopic surgery for middle and low rectal cancer (REAL): short-term outcomes of a multicentre randomised controlled trial.

Emerging Trends in the Etiology, Prevention, and Treatment of Gastrointestinal Anastomotic Leakage.

MicroRNAs (miRNAs) are small noncoding RNAs playing a fundamental role in the regulation of gene expression. Evidence accumulating in the past decades indicate that they are capable of simultaneously modulating diverse signaling pathways involved in a variety of pathophysiological processes. In the present review, we provide a comprehensive overview of the function of a highly conserved group of miRNAs, the miR-181 family, both in physiological as well as in pathological conditions. We summarize a large body of studies highlighting a role for this miRNA family in the regulation of key biological processes such as embryonic development, cell proliferation, apoptosis, autophagy, mitochondrial function, and immune response. Importantly, members of this family have been involved in many pathological processes underlying the most common neurodegenerative disorders as well as different solid tumors and hematological malignancies. The relevance of this miRNA family in the pathogenesis of these disorders and their possible influence on the severity of their manifestations will be discussed. A better understanding of the miR-181 family in pathological conditions may open new therapeutic avenues for devasting disorders such as neurodegenerative diseases and cancer.

https://www.mdpi.com/1422-0067/21/6/2092/pdf

The Pervasive Role of the miR-181 Family in Development, Neurodegeneration, and Cancer

The objective of this meta-analysis was to compare the clinical and oncologic outcomes of robotic low anterior resection (R-LAR) with conventional laparoscopic low anterior resection (L-LAR). A search in the MEDLINE, Embase, and Ovid databases was performed for studies published before July 2014 that compared the clinical and oncologic outcomes of R-LAR and L-LAR. The methodological quality of the selected studies was assessed. Depending on statistical heterogeneity, a fixed or random effects model was used for the meta-analysis. The clinical and oncologic outcomes evaluated included operative time, estimated blood loss, length of hospital stay, rate of conversion to open surgery, post-operative complications, circumferential margin status, and number of lymph nodes collected. Eight studies, including 324 R-LAR cases and 268 conventional L-LAR cases, were analyzed. The meta-analysis showed that R-LAR was associated with a shorter hospital stay (mean difference (MD) = −1.03; 95 % confidence interval (CI) = −1.78, −0.28; P = 0.007), lower conversion rate (odds ratio (OR) = 0.08; 95 % CI = 0.02, 0.31; P = 0.0002), lower rate of circumferential margin involvement (OR = 0.5; 95 % CI = 0.25, 1.01; P = 0.05), and lower overall complication rate (MD = 0.65; 95 % CI = 0.43, 0.99; P = 0.04) compared with L-LAR. There was no difference in operative time (MD = 28.4; 95 % CI = −3.48, 60.27; P = 0.08), the number of lymph nodes removed (MD = −0.63; 95 % CI = −0.78, 2.05; P = 0.38), and days to return of bowel function (MD = −0.15; 95 % CI = −0.37, 0.06; P = 0.17). R-LAR was shown to be associated with a shorter hospital stay, lower conversion rate, lower rate of circumferential margin involvement, and lower overall complication rate compared with L-LAR. There were no differences in operative time, the number of lymph nodes removed, and days to return of bowel function.

/pdf/robotic-versus-laparoscopic-low-anterior-resection-for-4tex44k7cg.pdf

Robotic versus laparoscopic low anterior resection for rectal cancer: a meta-analysis.

The emerging role of microRNA-181A (miR-181A) in CRC patients with late liver metastases was studied. In the present study we investigated the association between expression and mechanism of miRNA-181A, liver metastasis and prognosis of colorectal cancer (CRC). The expression of miR-181A and PTEN in CRC patients with late liver metastases was higher than that of the normal (control) group, whereas the expression of miR-181A and PTEN was lower in all pathological groups (TNM I-TNM IV). Overall survival (OS) of lower expression miR-181A CRC patients with late liver metastases was higher than that of higher expression miR-181A CRC patients with late liver metastases. The expression of miR-181A and PTEN in the colon cell line NCM460 was lower than that of the colon cancer SW620 cell line. Upregulation of miR-181A promoted cell viability and inhibited apoptosis of SW620 cells, suppressed PTEN expression and activated phosphorylation of AKT (p-AKT) in SW620 cells. Additionally, downregulation of miR-181A inhibited cell viability of SW620 cells through promotion of PTEN and inhibition of p-AKT. Together, our results indicate that miR-181A expression is associated with CRC patients with late liver metastases through PTEN/AKT signaling.

/pdf/expression-and-mechanism-of-microrna-181a-on-incidence-and-26av5pzzth.pdf

Expression and mechanism of microRNA-181A on incidence and survival in late liver metastases of colorectal cancer

Bcl2-associated athanogene 3 (BAG3) has been reported to be elevated in various tumors. However, it is unclear whether BAG3 has a functional role in the initiation and progression of colorectal cancer (CRC). Here, we collected CRC samples and cell lines to validate the pathway by using gene and protein assays. RT-PCR showed that the expression of BAG3 mRNA in CRC tissues was obviously higher than that in non-tumor tissues (p < 0.001). Immunohistochemical analysis showed that immunoreactivity of BAG3 was found in most CRC tissues and strongly correlated with TNM stage (p = 0.001), differentiation (p = 0.003), and metastasis (p = 0.010). Low expression of BAG3 in HCT-8 significantly reduced cellular proliferation, migration, and invasion. The analysis of in vitro cell showed that HCT-8 cells were exposed to si-BAG3, and its growth was inhibited depending on modulation of cell cycle G1/S checkpoints and cell cycle regulators, involving cyclin D1, cyclin A2, and cyclin B1. Furthermore, suppression of the epithelial-mesenchymal transition (EMT) by si-BAG3 is linked to the decreased expression of E-cadherin and the increased expression of N-cadherin, vimentin, and MMP9. In conclusion, in the present study, we demonstrated that BAG3 overexpression plays a critical role in cell proliferation, migration, and invasion of colorectal cancer. Our data suggests targeted inhibition of BAG3 may be useful for patients with CRC.

BAG3 regulates cell proliferation, migration, and invasion in human colorectal cancer.

Abstract Background Colorectal cancer (CRC) is the second leading cause of cancer-related deaths globally. It is essential to identify new CRC-associated therapeutic targets and diagnostic biomarkers. Previous studies have demonstrated that a series of circular RNAs (circRNAs) play a crucial role in CRC pathogenesis. This study assessed the potential of hsa_circ_0064559 in tumor cell growth and progression of CRC. Methods Six pairs of matched CRC and normal colorectal tissue samples were sequenced using the Affymetrix Clariom D array. Using RNA interference, the expression of thirteen circRNAs was knocked down in CRC cells. The proliferation of CRC cell lines (RKO and SW620 cells) was detected using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Apoptosis and cell cycle were determined by flow-cytometric analysis. An in vivo study uses nude mice to establish a CRC mouse model. The differentially expressed genes were analyzed using Affymetrix primeview human GeneChip array and verified by polymerase chain reaction. Results Affymetrix Clariom D array analysis revealed that thirteen circRNAs were upregulated in CRC. The proliferation of CRC cell lines was decreased, while the proportion of apoptotic and G1 phase cells was higher after hsa_circ_0064559 knockdown. In vivo xenograft nude mice model revealed that the volume and weight of the tumor were reduced by hsa_circ_0064559 knockdown. In Affymetrix primeview human GeneChip array, we found six upregulated genes (STAT1, ATF2, TNFRSF10B, TGFBR2, BAX, and SQSTM1) and two downregulated genes (SLC4A7 and CD274) related to apoptosis and proliferation of colorectal cancer cells after hsa_circ_0064559 knockdown. Conclusions The hsa_circ_0064559 knockdown could inhibit the proliferation, promote apoptosis in CRC cell lines in vitro, and inhibit the development of CRC tumors in vivo. The mechanism may be related to activating a wide range of signaling pathways. The hsa_circ_0064559 may be a potential biomarker for early diagnosis or prognosis of CRC and a novel drug target for CRC therapy. 

/pdf/circular-rna-hsa-circ-0064559-affects-tumor-cell-growth-and-28fknbsu.pdf

Circular RNA hsa_circ_0064559 affects tumor cell growth and progression of colorectal cancer

Objective
To investigate the expression level of high mobility group box-1 (HMGB1) in human colorectal cancer and its relation with different clinicopathological characteristics and prognosis of colorectal cancer patients.


Methods
Immunohistochemical method was used to detect the HMGB1 expression in tissue samples of 86 colorectal cancer patients and 32 normal colorectal tissue samples. Positive rates of HMGB1 expression were compared among different clinicopathological characteristics. Relation of HMGB1 expression with survival was analyzed.


Results
HMGB1 expression was mainly in colorectal cancer cell nucleus, with a few appearance of co-expression in nucleus and cytoplasm. Positive rate of HMGB1 expression in normal tissues was significantly lower than that in colorectal cancers [9.4% (3/32) vs. 66.3% (57/86) , P=0.000], and it was much higher in large cancers, lower differentiation, invasion to outside serosa, advanced clinical stage and lymph node metastasis (all P 0.05) . Survival analysis showed that 3-year survival rate of patients with positive HMGB1 expression was significantly lower as compared to those with negative HMGB1 expression (56.1% vs. 85.7%, P=0.021) , meanwhile it was significantly lower in patients with co-expression in nucleus and cytoplasm as compared to those with simple nuclear expression (41.4% vs. 75.0%, P=0.013) .


Conclusions
HMGB1 expression in colorectal cancer is high, and its positive rate increases with the low differentiation, invasion and metastasis. HMGB1 co-expression in nucleus and cytoplasm indicates poor prognosis of colorectal cancer patients.


Key words: 
Colorectal neoplasms; High mobility group box-1 (HMGB1); Immunohistochemistry; Clinical pathological features; Prognosis

[Expression of high mobility group box-1 in colorectal cancer and its clinical significance].

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