Conventional hemorrhoidectomy is the mainstay of treatment for symptomatic haemorrhoids, but reported postoperative complications remains the main concern. On the contrary, with its minimally invasive nature, laser hemorrhoidoplasty showed the potential to reduce postoperative complications and discomfort. Therefore, we performed a systemic review and meta-analysis to evaluate the postoperative outcome of laser hemorrhoidoplasty compared to conventional hemorrhoidectomies, including Milligan-Morgan and Ferguson techniques. Of all studies from PubMed, EMBASE, Cochrane database, and Google Scholar, we included 17 trials with 1196 patients, of whom 596 (49.8 %) underwent laser hemorrhoidoplasty and 600 (50.2 %) underwent conventional hemorrhoidectomy. The primary outcomes were operative blood loss and postoperative haemorrhage, and the secondary outcomes were the operative time, postoperative pain score, complications, and haemorrhoid recurrence. In this study, we found that laser hemorrhoidoplasty showed benefits in operative blood loss (weighted mean difference [WMD]: -16.43 ml, 95 % confidence interval [CI]: -23.82 to -9.04), postoperative hemorrhage/bleeding (odds ratio [OR]: 0.16, 95 % CI: 0.10 to 0.28), operative time (WMD: -12.42 min, 95 % CI: -14.56 to -10.28), postoperative pain score on day 1 (WMD: -2.50, 95 % CI: -3.13 to -1.88), and anal stenosis (OR: 0.14, 95 % CI: 0.03 to 0.65) in comparison with conventional hemorrhoidectomy. However, incidence of fecal/flatus incontinence, urinary retention and hemorrhoid recurrence were not significantly different between the 2 groups. Consistent results were found in 5 subgroup analyses, including studies with low risk of bias, studies using 1470 nm laser, and studies using 980 nm laser, studies conducted in Asia, and studies conducted in Europe and America.

Colorectal cancer represents one of the most prevalent malignancies globally, with an estimated 140,000 new cases in the United States alone in 2019. Despite advancements in interventions, drug resistance occurs in virtually all patients diagnosed with late stages of colon cancer. Amplified epidermal growth factor receptor (EGFR) signaling is one of the most prevalent oncogenic drivers in patients and induces increased Janus kinase (JAK)/signal transduction and activator of transcription (STAT) and β-catenin functions, all of which facilitate disease progression. Equally important, cancer-associated fibroblasts (CAFs) transformed by cancer cells within the tumor microenvironment (TME) further facilitate malignancy by secreting interleukin (IL)-6 and augmenting STAT3 signaling in colon cancer cells and promoting the generation of cancer stem-like cells (CSCs). Based on these premises, single-targeted therapeutics have proven ineffective for treating malignant colon cancer, and alternative multiple-targeting agents should be explored. Herein, we synthesized a tetracyclic heterocyclic azathioxanthone, MSI-N1014, and demonstrated its therapeutic potential both in vitro and in vivo. First, we used a co-culture system to demonstrate that colon cancer cells co-cultured with CAFs resulted in heightened 5-fluorouracil (5-FU) resistance and tumor sphere-forming ability and increased side populations, accompanied by elevated expression of cluster of differentiation 44 (CD44), β-catenin, leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), and ATP-binding cassette super-family G member 2 (ABCG2). MSI-N1014 suppressed cell viability, colony formation, and migration in both DLD1 and HCT116 cells. MSI-N1014 treatment led to decreased expressions of oncogenic markers, including mammalian target of rapamycin (mTOR), EGFR, and IL-6 and stemness markers such as CD44, β-catenin, and LGR5. More importantly, MSI-N1014 treatment suppressed the transformation of CAFs, and was associated with decreased secretion of IL-6 and vascular endothelial growth factor (VEGF) by CAFs. Furthermore, MSI-N1014 treatment resulted in significantly reduced oncogenic properties, namely the migratory ability, tumor-sphere generation, and resistance against 5-FU. Notably, an increased level of the tumor suppressor, miR-142-3p, whose targets include LGR5, IL-6, and ABCG2, was detected in association with MSI-N1014 treatment. Finally, we demonstrated the therapeutic potential of MSI-N1014 in vivo, where combined treatment with MSI-N1014 and 5-FU led to the lowest tumor growth, followed by MSI-N1014 only, 5-FU, and the vehicle control. Tumor samples from the MSI-N1014 group showed markedly reduced expressions of LGR5, β-catenin, IL-6, and mTOR, but increased expression of the tumor suppressor, miR-142-3p, according to qRT-PCR analysis. Collectively, we present preclinical support for the application of MSI-N1014 in treating 5-FU-resistant colon cancer cells. Further investigation is warranted to translate these findings into clinical settings.

Metastasis remains the major cause of death from colon cancer. We intend to identify differentially expressed genes that are associated with the metastatic process and prognosis in colon cancer. ATP synthase epsilon subunit (ATP5E) gene was found to encode the mitochondrial F₀F₁ ATP synthase subunit epsilon that was overexpressed in tumor cells compared to their normal counterparts, while other genes encoding the ATP synthase subunit were repressed in public microarray datasets. CRC cells in which ATP5E was silenced showed markedly reduced invasive and migratory abilities. ATP5E inhibition significantly reduced the incidence of distant metastasis in a mouse xenograft model. Mechanistically, increased ATP5E expression resulted in a prominent reduction in E-cadherin and an increase in Snail expression. Our data also showed that an elevated ATP5E level in metastatic colon cancer samples was significantly associated with the AMPK-AKT-hypoxia-inducible factor-1α (HIF1α) signaling axis; silencing ATP5E led to the degradation of HIF1α under hypoxia through AMPK-AKT signaling. Our findings suggest that elevated ATP5E expression could serve as a marker of distant metastasis and a poor prognosis in colon cancer, and ATP5E functions via modulating AMPK-AKT-HIF1α signaling.

5-Fluorouracil (5-FU) regimen remains the backbone of the first-line agent to treat colon cancer, but often these patients develop resistance. Cancer stem cells (CSC’s) are considered as one of the key contributors in the development of drug resistance and tumor recurrence. We aimed to provide preclinical evidence for Antrodia cinnamomea (AC), as a potential in suppressing colon cancer CSC’s to overcome 5-FU drug-resistant. In-vitro assays including cell viability, colony formation, AC + 5-FU drug combination index and tumor sphere generation were applied to determine the inhibitory effect of AC. Mouse xenograft models also incorporated to evaluate in vivo effect of AC. AC treatment significantly inhibited the proliferation, colony formation and tumor sphere generation. AC also inhibited the expression of oncogenic markers (NF-κB, and C-myc), EMT/metastasis markers (vimentin and MMP3) and stemness associated markers (β-catenin, SOX-2 and Nanog). Sequential treatment of AC and 5-FU synergized and reduces colon cancer viability both in vivo and in vitro. Mechanistically, AC mediated anti-tumor effect was associated with an increased level of tumor suppressor microRNAs especially, miR142-3p. AC can be a potent synergistic adjuvant, down-regulates cancer stemness genes and enhances the antitumor ability of 5-FU by stimulating apoptosis-associated genes, suppressing inflammation and metastasis genes through miR142-3p in colon cancer.

Background/objective: The reduced-port approach can overcome the limitations of single-incision lapa-roscopic surgery while maintaining its advantages. Here, we compared the effects of robotic reduced -port surgery and conventional laparoscopic approaches for left-sided colorectal cancer.Methods: Between January 2015 and December 2016, the clinicopathological characteristics and treat-ment outcomes of 17 patients undergoing robotic reduced-port surgery and 49 patients undergoing laparoscopic surgery for left-sided colorectal cancer were compared.Results: The two groups were comparable in almost all outcome measures except for the distal resection margin, which was significantly longer in the laparoscopic group (P < 0.001). The between-group dif-ferences in reoperation, incisional hernia development, and overall and progression-free survival were nonsignificant; however, the total hospital cost was significantly higher in the robotic group than in the laparoscopic group (US$13779.6 +/- US$3114.8 vs. US$8556.3 +/- US$2056.7, P < 0.001). Conclusion: Robotic reduced-port surgery for left-sided colorectal cancer is safe and effective but more expensive with no additional benefit compared with the conventional laparoscopic approach. This observation warrants further evaluation.(c) 2023 Asian Surgical Association and Taiwan Robotic Surgery Association. Publishing services by Elsevier B.V. All rights reserved. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).

Tumor recurrence from cancer stem cells (CSCs) and metastasis often occur post-treatment in colorectal cancer (CRC), leading to chemoresistance and resistance to targeted therapy. MYC is a transcription factor in the nuclei that modulates cell growth and development, and regulates immune response in an antitumor direction by mediating programmed death ligand 1 (PD-L1) and promoting CRC tumor recurrence after adjuvant chemotherapy. However, the molecular mechanism through which c-MYC maintains stemness and confers treatment resistance still remains elusive in CRC. In addition, recent reports demonstrated that CRC solid colon tumors expresses C-X-C motif chemokine ligand 8 (CXCL8). Expression of CXCL8 in CRC was reported to activate the expression of PD-L1 immune checkpoint through c-MYC, this ultimately induces chemoresistance in CRC. Accumulating studies have also demonstrated increased expression of CXCL8, matrix metalloproteinase 7 (MMP7), tissue inhibitor of metalloproteinase 1 (TIMP1), and epithelial-to-mesenchymal transition (EMT) components, in CRC tumors suggesting their potential collaboration to promote EMT and CSCs. TIMP1 is MMP-independent and regulates cell development and apoptosis in various cancer cell types, including CRC. Recent studies showed that TIMP1 cleaves CXCL8 on its chemoattractant, thereby influencing its mechanistic response to therapy. This therefore suggests crosstalk among the c-MYC/CXCL8/TIMP1 oncogenic signatures. In this study, we explored computer simulations through bioinformatics to identify and validate that the MYC/CXCL8/TIMP1 oncogenic signatures are overexpressed in CRC, Moreover, our docking results exhibited putative binding affinities of the above-mentioned oncogenes, with our novel small molecule, RV59, Finally, we demonstrated the anticancer activities of RV59 against NCI human CRC cancer cell lines both as single-dose and dose-dependent treatments, and also demonstrated the MYC/CXCL8/TIMP1 signaling pathway as a potential RV59 drug target.