Risk factors for anastomotic leak and postoperative morbidity after right hemicolectomy for colon cancer: results from a prospective, multi-centre, snapshot study in China.

BACKGROUND: Right hemicolectomy is the standard treatment for right-sided colon cancer. There is variation in the technical aspects of performing right hemicolectomy as well as in short-term outcomes. It is therefore necessary to explore best clinical practice following right hemicolectomy in expert centres. METHODS: This snapshot study of right hemicolectomy for colon cancer in China was a prospective, multicentre cohort study in which 52 tertiary hospitals participated. Eligible patients with stage I-III right-sided colon cancer who underwent elective right hemicolectomy were consecutively enrolled in all centres over 10 months. The primary endpoint was the incidence of postoperative 30-day anastomotic leak. RESULTS: Of the 1854 patients, 89.9 per cent underwent laparoscopic surgery and 52.3 per cent underwent D3 lymph node dissection. The overall 30-day morbidity and mortality were 11.7 and 0.2 per cent, respectively. The 30-day anastomotic leak rate was 1.4 per cent. In multivariate analysis, ASA grade > II (P < 0.001), intraoperative blood loss > 50 ml (P = 0.044) and D3 lymph node dissection (P = 0.008) were identified as independent risk factors for postoperative morbidity. Extracorporeal side-to-side anastomosis (P = 0.031), intraoperative blood loss > 50 ml (P = 0.004) and neoadjuvant chemotherapy (P = 0.004) were identified as independent risk factors for anastomotic leak. CONCLUSION: In high-volume expert centres in China, laparoscopic resection with D3 lymph node dissection was performed in most patients with right-sided colon cancer, and overall postoperative morbidity and mortality was low. Further studies are needed to explore the optimal technique for right hemicolectomy in order to improve outcomes further.

Exosomal circRNAs as novel potential biomarkers for colorectal adenoma.

Growing evidences have revealed that exosomal miRNAs, lncRNAs, and circRNAs play a pleiotropic role in tumor biology. Cell-cell communication mediated by exosomes has been considered to be a key factor in the malignant progression of colorectal cancer. However, the importance of exosome-derived circRNAs in the biological function and clinical significance of colorectal adenoma remains elusive. In this study, we aimed to identify altered circRNA expression profiles in exosomes isolated from plasma of patients with colorectal adenoma using high-throughput sequencing. Exosomes were confirmed by western blotting, transmission electron microscopy, and NanoSight assay. The sequencing data indicated that there are 413 differentially expressed circRNAs including 112 upregulated and 301 downregulated circRNAs in colorectal adenoma patients compared with controls. GO analysis and the circRNA-miRNA-mRNA network were performed to predict the potential function of circRNAs, and demonstrate the putative mechanisms in colorectal adenoma. Collectively, our findings revealed that plasma exosomal circRNAs may be a potential noninvasive biomarker for the detection of colorectal adenoma, and provided new insights into colorectal adenoma-carcinoma sequence.

Preoperative Hepatic and Regional Arterial Chemotherapy in Patients Who Underwent Curative Colorectal Cancer Resection: A Prospective, Multi-center, Randomized Controlled Trial.

OBJECTIVE: To evaluate the effects of the addition of preoperative hepatic and regional arterial chemotherapy (PHRAC) on prognosis of stage II and III colorectal cancer (CRC) in a multicenter setting. SUMMARY OF BACKGROUND DATA: Our previous single-center pilot trial suggested that PHRAC in combination with surgical resection could reduce the occurrence of liver metastasis (LM) and improve survival in CRC patients. METHODS: A prospective multi-center randomized controlled trial was conducted from December 2008 to December 2012 at 5 hospitals in China. Eligible patients with clinical stage II or III CRC who underwent curative resection were randomized to receive PHRAC plus adjuvant therapy (PHRAC arm) or adjuvant therapy alone (control arm). The primary endpoint was DFS. Secondary endpoints were cumulative LM rates, overall survival (OS), and safety (NCT00643877). RESULTS: A total of 688 patients from 5 centers in China were randomly assigned (1:1) to each arm. The five-year DFS rate was 77% in the PHRAC arm and 65% in the control arm (HR = 0.61, 95% CI 0.46-0.81; P = 0.001). The 5-year LM rates were 7% and 16% in the PHRAC and control arms, respectively (HR = 0.37, 95% CI 0.22-0.63; P < 0.001). The 5-year OS rate was 84% in the PHRAC arm and 76% in the control arm (HR = 0.61, 95% CI 0.43-0.86; P = 0.005). There were no significant differences regarding treatment related morbidity or mortality between the two arms. CONCLUSIONS: The addition of PHRAC could improve DFS in patients with stage II and III CRC. It reduced the incidence of LM and improved OS without compromising patient safety. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00643877.

Hand-assisted laparoscopic surgery compared with open resection for mid and low rectal cancer: a case-matched study with long-term follow-up.

BACKGROUND: This study was designed to compare the long-term surgical outcomes of patients with mid and low rectal cancer after open or hand-assisted laparoscopic surgery (HALS). METHODS: A case-matched controlled prospective analysis of 116 patients who underwent hand-assisted laparoscopic surgery (HALS) for stage I to III mid and low rectal cancer from 2005 to 2010 was performed. Contemporary patients who underwent open rectal surgery were matched to the HALS group at the ratio of 1:1. The perioperative clinical outcomes, postoperative pathology, and survival outcomes were compared between the groups. RESULTS: The patient characteristics between the two groups were comparable. Ninety patients in the open group and 85 in the HALS group received sphincter-preserving surgery. HALS resulted in less blood loss and wound infection, faster return to oral diet, shorter postoperative hospital stay, and longer operating time. The two groups had similar complication rates. Lymph node retrieval and involvement of circumferential and distal margins were similar for both procedures. Cumulative incidences of locoregional recurrence, disease-free, or overall survival rates were statistically similar. CONCLUSIONS: This study suggests that HALS for mid and low rectal cancer is acceptable in terms of short-term clinical outcomes and long-term survival results.

Clostridium difficile carriage in hospitalized cancer patients: a prospective investigation in eastern China.

BACKGROUND: Clostridium difficile carriage has been considered as a potential source for the deadly infection, but its role in cancer patients is still unclear. We aimed to identify the clinical and immunological factors that are related to C. difficile carriage in Chinese cancer patients. METHODS: A total of 400 stool samples were collected from cancer patients who received chemotherapy in three hospitals of eastern China. Bacterial genomic DNA was extracted and two toxin genes (tcdA and tcdB) were detected. PCR ribotyping was performed using capillary gel electrophoresis. Concentrations of prostaglandin E2 (PGE2), transforming growth factor beta (TGF-ß) and interleukin-10 (IL-10) were measured using enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: Eighty-two (20.5%) samples were confirmed to be C. difficile-positive and positive for tpi, tcdA, and tcdB genes. The C. difficile-positive rates in patients with diarrhea and no diarrhea were 35% and 19.7%, respectively (p = 0.09). Patients who were younger than 50 years old and were hospitalized for at least 10 days had a C. difficile-positive rate as high as 35%. In contrast, patients who were older than 50 years old and were hospitalized for less than 10 days had a C. difficile-positive rate of only 12.7% (p = 0.0009). No association was found between C. difficile carriage and chemotherapy regimen, antibiotic drug use, or immunosuppressive mediators, such as prostaglandin E2 (PGE2), transforming growth factor beta (TGF-ß), or interleukin-10 (IL-10). Twelve ribotypes of C. difficile were identified, but none of them belonged to ribotype 027. CONCLUSIONS: We conclude that younger patients and those with longer hospitalization stays may be more prone to C. difficile carriage. Studies of larger populations are warranted to clarify the exact role of C. difficile carriage in hospitalized cancer patients in China.

COLORECTAL Polymeric Immunoglobulin Receptor Expression is Correlated with Hepatic Metastasis and Poor Prognosis in Colon Carcinoma Patients with Hepatic Metastasis.

BACKGROUND/AIMS: Increased expression of polymeric immunoglobulin receptor (pIgR) in tumor tissue has been detected in various cancer forms. However, the clinical relevance of pIgR in colon cancer hepatic metastasis remains uncertain. The aim of this study was to assess the prognostic value of pIgR in patients with colon carcinoma hepatic metastasis after hepatic resection. METHODOLOGY: Genome-wide gene expression analysis was used to evaluate the expression of pIgR in cryopreserved tissue from liver metastases of colon cancer and in the corresponding primary colon cancer tissues from one patient with hepatic metastatic colon cancer. pIgR expression was further confirmed by quantitative real-time PCR in cryopreserved primary colon carcinoma and paired hepatic metastasis tissues from 32 patients with hepatic metastatic colon cancer and by immunohistochemistry in paraffin-embedded primary colon carcinoma and paired hepatic metastasis tissues from 136 patients with liver metastasis from colon carcinoma who underwent hepatic resection. The relation between pIgR expression and clinicopathologic factors and long-term prognosis in these 136 patients was retrospectively examined. The prognostic significance of negative or positive pIgR exspression in colon carcinoma hepatic metastasis was assessed using Kaplan-Meier survival analysis and log-rank tests. RESULTS: Positive expression of pIgR was correlated with liver metastasis of colon cancer. Univariate analysis indicated significantly worse overall survival (OS) for patients with a positive pIgR expression in colon carcinoma hepatic metastasis than for patients with a negative pIgR expression. Multivariate analysis showed positive-pIgR in colon carcinoma hepatic metastasis to be an independent prognostic factor for OS after hepatic resection (P = 0.021). CONCLUSIONS: Positive expression of pIgR was statistically significantly associated with poor prognosis of patients with colon carcinoma hepatic metastasis. pIgR could be a novel predictor for poor prognosis of patients with colon carcinoma hepatic metastasis after hepatic resection.

Current landscape of preoperative neoadjuvant therapies for initial resectable colorectal cancer liver metastasis.

Colorectal cancer liver metastasis (CRLM) presents a clinical challenge, and optimizing treatment strategies is crucial for improving patient outcomes. Surgical resection, a key element in achieving prolonged survival, is often linked to a heightened risk of recurrence. Acknowledging the potential benefits of preoperative neoadjuvant chemotherapy in managing resectable liver metastases, this approach has gained attention for its role in tumor downsizing, assessing biological behavior, and reducing the risk of postoperative recurrence. However, the use of neoadjuvant chemotherapy in initially resectable CRLM sparks ongoing debates. The balance between tumor reduction and the risk of hepatic injury, coupled with concerns about delaying surgery, necessitates a nuanced approach. This article explores recent research insights and draws upon the practical experiences at our center to address critical issues regarding considerations for initially resectable cases. Examining the criteria for patient selection and the judicious choice of neoadjuvant regimens are pivotal areas of discussion. Striking the right balance between maximizing treatment efficacy and minimizing adverse effects is imperative. The dynamic landscape of precision medicine is also reflected in the evolving role of gene testing, such as RAS/BRAF and PIK3CA, in tailoring neoadjuvant regimens. Furthermore, the review emphasizes the need for a multidisciplinary approach to navigate the complexities of CRLM. Integrating technical expertise and biological insights is crucial in refining neoadjuvant strategies. The management of progression following neoadjuvant chemotherapy requires a tailored approach, acknowledging the diverse biological behaviors that may emerge. In conclusion, this review aims to provide a comprehensive perspective on the considerations, challenges, and advancements in the use of neoadjuvant chemotherapy for initially resectable CRLM. By combining evidence-based insights with practical experiences, we aspire to contribute to the ongoing discourse on refining treatment paradigms for improved outcomes in patients with CRLM.

Heterogeneity-related anticancer therapy response differences in metastatic colon carcinoma: new hints to tumor-site-based personalized cancer therapy.

BACKGROUND/AIMS: Heterogeneity in primary tumor and related metastases may result in different response to anticancer therapy. Previous work revealed that there were heterogeneity in primary colon carcinoma and matched lymphatic and hepatic metastases. Whether such heterogeneity in primary colon carcinoma and corresponding lymphatic and hepatic metastases would result in different response to anticancer therapy is unknown. METHODOLOGY: To investigate whether the heterogeneity in primary colon carcinoma and matched lymphatic and hepatic metastases would result in different response to anticancer therapy, patient-derived tumor tissue (PDTT) xenograft models of colon carcinoma with lymphatic and hepatic metastases were used to evaluate the response to VEGF-targeted therapy (bevacizumab) in combination with chemotherapy (capecitabine). RESULTS: All xenografts of primary colon carcinoma and corresponding lymphatic and hepatic metastases in nude mice responded to VEGF-targeted therapy in combination with chemotherapy. However, chemotherapy alone resulted in significantly higher tumor growth inhibition rate in xenogfafts of primary colon carcinoma than that of corresponding lymphatic and hepatic metastasis (p < 0.01). VEGF-targeted therapy in combination with chemotherapy resulted in significantly higher tumor growth inhibition rate in xenogfafts of colon carcinoma lymphatic metastasis than that of corresponding primary colon carcinoma and hepatic metastasis (p < 0.001). CONCLUSIONS: Our results demonstrate that primary colon carcinoma and its corresponding lymphatic and hepatic metastases have different response rate to chemotherapy and to VEGF-targeted therapy in combination with chemotherapy. This study provides us new hints to tumor-site-based personalized cancer therapy in metastatic colon carcinoma.

Can immunotherapy reinforce chemotherapy efficacy? a new perspective on colorectal cancer treatment.

As one of the main threats to human life (the fourth most dangerous and prevalent cancer), colorectal cancer affects many people yearly, decreases patients' quality of life, and causes irreparable financial and social damages. In addition, this type of cancer can metastasize and involve the liver in advanced stages. However, current treatments can't completely eradicate this disease. Chemotherapy and subsequent surgery can be mentioned among the current main treatments for this disease. Chemotherapy has many side effects, and regarding the treatment of this type of tumor, chemotherapy can lead to liver damage, such as steatohepatitis, steatosis, and sinus damage. These damages can eventually lead to liver failure and loss of its functions. Therefore, it seems that other treatments can be used in addition to chemotherapy to increase its efficiency and reduce its side effects. Biological therapies and immunotherapy are one of the leading suggestions for combined treatment. Antibodies (immune checkpoint blockers) and cell therapy (DC and CAR-T cells) are among the immune system-based treatments used to treat tumors. Immunotherapy targets various aspects of the tumor that may lead to 1) the recruitment of immune cells, 2) increasing the immunogenicity of tumor cells, and 3) leading to the elimination of inhibitory mechanisms established by the tumor. Therefore, immunotherapy can be used as a complementary treatment along with chemotherapy. This review will discuss different chemotherapy and immunotherapy methods for colorectal cancer. Then we will talk about the studies that have dealt with combined treatment.

Cholesterol in colorectal cancer: an essential but tumorigenic precursor?

Colorectal cancer (CRC) is one of the most lethal human malignancies, and with the growth of societies and lifestyle changes, the rate of people suffering from it increases yearly. Important factors such as genetics, family history, nutrition, lifestyle, smoking, and alcohol can play a significant role in increasing susceptibility to this cancer. On the other hand, the metabolism of several macromolecules is also involved in the fate of tumors and immune cells. The evidence discloses that cholesterol and its metabolism can play a role in the pathogenesis of several cancers because there appears to be an association between cholesterol levels and CRC, and cholesterol-lowering drugs may reduce the risk. Furthermore, changes or mutations of some involved genes in cholesterol metabolism, such as CYP7A1 as well as signaling pathways, such as mitogen-activated protein kinase (MAPK), can play a role in CRC pathogenesis. This review summarized and discussed the role of cholesterol in the pathogenesis of CRC as well as available cholesterol-related therapeutic approaches in CRC.

Multiple thread ligations versus stapled hemorrhoidopexy on operative outcomes of grade III hemorrhoids: A retrospective cohort study.

Object: Controversy remains regarding the safety and efficacy of hemorrhoid ligation and stapled hemorrhoidopexy (SH) in the treatment of hemorrhoids. The study was to explore the operative outcomes of patients underwent multiple thread ligations (MTL) with SH for the management of grade III hemorrhoids. Methods: This cohort study included patients who underwent MTL (MTL group, 128 cases) or SH (SH group, 141 cases) for grade III hemorrhoids between June 2019 and May 2021. A total of 115 patients in MTL group and 115 patients in SH group were finally included by propensity score matching with a ratio of 1:1. The primary outcome was the recurrence of prolapse within 6 months. Secondary outcomes were operative time, post-operative pain scores, hospital stay, the incidence of complications, Wexner incontinence score, and quality of life of patients with constipation at 6 months post procedure. Results: Multiple thread ligations and SH resulted in comparable recurrence within 6 months of follow-up, with five and seven cases of recurrence, respectively, (P = 0.352). The two groups had comparable outcomes in terms of post-operative pain, hospital stay, Wexner incontinence scores, and constipation-related quality of life (all P > 0.05). The median operative time was 16 min (15-18 min) in the MTL group versus 25 min (16-33 min) in the SH group (P < 0.01). Univariate analysis showed that the MTL technique had a lower risk of postoperative bleeding than that with the SH technique (P < 0.05). Conclusion: The study indicated that the MTL technique might achieve comparable operative outcomes compared with the SH technique for the management of grade III hemorrhoids, nevertheless, MTL seemed to be associated with less risk of surgical bleeding than SH.

Harnessing Ferroptosis to Overcome Drug Resistance in Colorectal Cancer: Promising Therapeutic Approaches.

Drug resistance remains a significant challenge in the treatment of colorectal cancer (CRC). In recent years, the emerging field of ferroptosis, a unique form of regulated cell death characterized by iron-dependent lipid peroxidation, has offered new insights and potential therapeutic strategies for overcoming drug resistance in CRC. This review examines the role of ferroptosis in CRC and its impact on drug resistance. It highlights the distinctive features and advantages of ferroptosis compared to other cell death pathways, such as apoptosis and necrosis. Furthermore, the review discusses current research advances in the field, including novel treatment approaches that target ferroptosis. These approaches involve the use of ferroptosis inducers, interventions in iron metabolism and lipid peroxidation, and combination therapies to enhance the efficacy of ferroptosis. The review also explores the potential of immunotherapy in modulating ferroptosis as a therapeutic strategy. Additionally, it evaluates the strengths and limitations of targeting ferroptosis, such as its selectivity, low side effects, and potential to overcome resistance, as well as challenges related to treatment specificity and drug development. Looking to the future, this review discusses the prospects of ferroptosis-based therapies in CRC, emphasizing the importance of further research to elucidate the interaction between ferroptosis and drug resistance. It proposes future directions for more effective treatment strategies, including the development of new therapeutic approaches, combination therapies, and integration with emerging fields such as precision medicine. In conclusion, harnessing ferroptosis represents a promising avenue for overcoming drug resistance in CRC. Continued research efforts in this field are crucial for optimizing therapeutic outcomes and providing hope for CRC patients.

Specific intracellular retention of circSKA3 promotes colorectal cancer metastasis by attenuating ubiquitination and degradation of SLUG.

Our previous study demonstrated that tumor-suppressor circular RNAs (circRNAs) can be specifically secreted outside of colorectal cancer (CRC) cells within exosomes to maintain tumor cell fitness. However, whether tumor-driving circRNAs can be specifically retained in cells to facilitate tumor progression remains unknown. In this study, circRNA-seq showed that circSKA3 was significantly upregulated in CRC tissues but downregulated in serum samples from CRC patients. In addition, circSKA3 promoted CRC progression in vitro and in vivo and was retained in CRC cells via a specific cellmotif element. Interestingly, the cellmotif element was also the site of interaction of circSKA3 with SLUG, which inhibited SLUG ubiquitination degradation and promoted CRC epithelial-mesenchymal transition (EMT). Moreover, FUS was identified as a key circularization regulator of circSKA3 that bound to the key element. Finally, we designed and synthesized specific antisense oligonucleotides (ASOs) targeting circularization and cellmotif elements, which repressed circSKA3 expression, abolished the SLUG-circSKA3 interaction, and further inhibited CRC EMT and metastasis in vitro and in vivo.

Incidence, prevention, risk factors, and prediction of venous thromboembolism in Chinese patients after colorectal cancer surgery: a prospective, multicenter cohort study.

BACKGROUND: Venous thromboembolism (VTE) is a common and serious complication after colorectal cancer (CRC) surgery. Few large-sample studies have reported VTE incidence and management status after CRC surgery in China. This study aimed to investigate the incidence and prevention of VTE in Chinese patients after CRC surgery, identify risk factors for developing VTE, and construct a new scoring system for clinical decision-making and care planning. METHODS: Participants were recruited from 46 centers in 17 provinces in China. Patients were followed up for 1 month postoperatively. The study period was from May 2021 to May 2022. The Caprini score risk stratification and VTE prevention and incidence were recorded. The predictors of the occurrence of VTE after surgery were identified by multivariate logistic regression analysis, and a prediction model (CRC-VTE score) was developed. RESULTS: A total of 1836 patients were analyzed. The postoperative Caprini scores ranged from 1 to 16 points, with a median of 6 points. Of these, 10.1% were classified as low risk (0-2 points), 7.4% as moderate risk (3-4 points), and 82.5% as high risk (≥5 points). Among these patients, 1210 (65.9%) received pharmacological prophylaxis, and 1061 (57.8%) received mechanical prophylaxis. The incidence of short-term VTE events after CRC surgery was 11.2% (95% CI 9.8-12.7), including deep venous thrombosis (DVT) (11.0%, 95% CI 9.6-12.5) and pulmonary embolism (PE) (0.2%, 95% CI 0-0.5). Multifactorial analysis showed that age (≥70 years), history of varicose veins in the lower extremities, cardiac insufficiency, female sex, preoperative bowel obstruction, preoperative bloody/tarry stool, and anesthesia time at least 180 min were independent risk factors for postoperative VTE. The CRC-VTE model was developed from these seven factors and had good VTE predictive performance ( C -statistic 0.72, 95% CI 0.68-0.76). CONCLUSIONS: This study provided a national perspective on the incidence and prevention of VTE after CRC surgery in China. The study offers guidance for VTE prevention in patients after CRC surgery. A practical CRC-VTE risk predictive model was proposed.

[Hand-assisted laparoscopic surgery in radical resection of rectal cancer].

OBJECTIVE: To investigate the application experience and clinical effects of hand-assisted laparoscopic radical resection for rectal cancer. METHODS: The clinical data of 156 patients with rectal cancer treated with hand-assisted laparoscopic surgery between August 2009 and April 2011 were analyzed retrospectively. RESULTS: The operative procedures of 156 patients were completed successfully and 1 case was converted to laparotomy (0.6%). The mean operation time was (125 ± 35) minutes; the mean intraoperative blood loss was (118 ± 60) ml; the mean time of bowel function recovery was (60 ± 8) hours; the median postoperative hospital stay was (9.5 ± 2.2) days. The mean number of lymph nodes dissection was (14 ± 5). Five patients (3.2%) had postoperative complications. All the patients were followed up. There had been no local recurrence or trocar site implantation metastasis. CONCLUSION: Hand-assisted laparoscopic surgery approach for the curative resection of rectal cancer is safe and effective and has broad prospects in clinical application.

Prognostic impact of mitofusin 2 expression in colon cancer.

Background: Mitofusin 2 (MFN2) is involved in several biological processes, including cancer. MFN2 is downregulated in some types of cancer and inhibits cancer cell proliferation, migration, and invasion. However, the relationship between MFN2 and colon cancer remains unknown. Methods: In this study, MFN2 expression was investigated using The Cancer Genome Atlas (TCGA) and the Human Protein Atlas (HPA), and the associations between prognostic factors and survival outcomes were assessed via univariate and multivariate analyses. Functional enrichment analyses based on Kyoto Encyclopedia of Genes and Genomes (KEGG) resource and Gene Set Enrichment Analysis (GSEA) were carried out. Results: MFN2 was downregulated in colon cancer tissues compared with paracancerous colon tissues (P<0.001), and low MFN2 expression was associated with an advanced tumor stage (stage IV vs. stage I, P=0.03; stage I-III vs. stage IV, P=0.003). MFN2 immunohistochemistry (IHC) staining was medium to high in colon normal tissues, but MFN2 IHC staining was faint or not identified in colorectal cancer (CRC) tumor tissues. MFN2 expression was either low or non-existent in colon cancer distinct cell clusters, according to differential gene analysis. Univariate analysis revealed that MFN2 expression in colon cancer patients was significantly associated with the stage [odds ratio (OR) =0.29 for stage IV vs. stage I, P=0.001], T-stage (OR =0.20 for T4 vs. T1, P=0.033), and distant metastasis (OR =0.31 for M1 vs. M0, P=0.000). Furthermore, Kaplan-Meier survival analysis revealed that patients with colon cancer and high MFN2 expression have a better prognosis than those with low MFN2 expression (P=0.002). MFN2 (hazard ratio =0.95, 95% confidence interval: 0.92-0.99, P=0.007) was an independent predictor of colon cancer according to univariate and multivariate Cox models. Finally, GSEA results showed that the KEGG GALACTOSE METABOLISM, APOPTOSIS, and VEGF SIGNALING pathways were activated in the high MFN2 mRNA expression group, whereas the KEGG RIBOSOME pathway was inhibited in the low MFN2 expression group. Conclusions: Our research revealed MFN2 to be a promising predictive biomarker and therapeutic target for colon cancer.

Nomogram Predicting the Survival of Young-Onset Patients with Colorectal Cancer Liver Metastases.

Background: Although the global prevalence of colorectal cancer (CRC) is decreasing, there has been an increase in incidence among young-onset individuals, in whom the disease is associated with specific pathological characteristics, liver metastases, and a poor prognosis. Methods: From 2010 to 2016, 1874 young-onset patients with colorectal cancer liver metastases (CRLM) from the Surveillance, Epidemiology, and End Results (SEER) database were randomly allocated to training and validation cohorts. Multivariate Cox analysis was used to identify independent prognostic variables, and a nomogram was created to predict cancer-specific survival (CSS) and overall survival (OS). Receiver operating characteristic (ROC) curve, C-index, area under the curve (AUC), and calibration curve analyses were used to determine nomogram accuracy and reliability. Results: Factors independently associated with young-onset CRLM CSS included primary tumor location, the degree of differentiation, histology, M stage, N stage, preoperative carcinoembryonic antigen level, and surgery (all p < 0.05). The C-indices of the CSS nomogram for the training and validation sets (compared to TNM stage) were 0.709 and 0.635, and 0.735 and 0.663, respectively. The AUC values for 1-, 3-, and 5-year OS were 0.707, 0.708, and 0.755 in the training cohort and 0.765, 0.735, and 0.737 in the validation cohort, respectively; therefore, the nomogram had high sensitivity, and was superior to TNM staging. The calibration curves for the training and validation sets were relatively consistent. In addition, a similar result was observed with OS. Conclusions: We developed a unique nomogram incorporating clinical and pathological characteristics to predict the survival of young-onset patients with CRLM. This may serve as an early warning system allowing doctors to devise more effective treatment regimens.

Primary Tumor Resection Provides Survival Benefits for Patients with Synchronous Brain Metastases from Colorectal Cancer.

Background: Brain metastases (BMs), particularly synchronous brain metastases, in colorectal cancer (CRC) patients are uncommon. The survival benefit of primary tumor resection (PTR) in patients with metastatic colorectal cancer is controversial. Whether PTR can bring survival benefits to patients with BMs of CRC has not been reported. Methods: From 2010 to 2016, 581 CRC patients with BMs from the Surveillance, Epidemiology, and End Results (SEER) database were divided into PTR and non-PTR groups. The log-rank test was used to compare the survival distributions. The Kaplan-Meier method was used to estimate survival. By controlling additional prognostic factors, a Cox proportional multivariate regression analysis was used to estimate the survival benefit of PTR. Results: The median overall survival for CRC patients with synchronous BMs was 3 months, with a 1-year survival rate of 27.2% and a 2-year survival rate of 12.8%. The PTR group contained 171 patients (29.4%), whereas the non-PTR group had 410 patients (70.6%). Patients who underwent PTR had a 1-year survival rate of 40.2% compared to 21.7% in those who did not (p < 0.0001). Cox proportional analysis showed that patients ≥60 years (hazard ratio [HR] 1.718, 95% confidence interval [CI] 1.423−2.075, p < 0.0001) had a shorter OS than patients < 60 years of age. OS was better in CEA-negative than in CEA-positive patients (HR 0.652, 95% CI 0.472−0.899, p = 0.009). Patients in whom the primary tumor was removed had considerably improved prognoses (HR 0.654, 95% CI 0.531−0.805, p < 0.0001). Subgroup analysis revealed that the PTR group achieved a survival advantage except for patients with CEA negative. Conclusions: Patients with synchronous BMs from CRC may benefit from primary tumor resection (PTR). Age, CEA level, and PTR were independent prognostic risk factors for CRC patients with synchronous BMs.

Menstrual Blood-Derived Stem Cells as Delivery Vehicles for Oncolytic Adenovirus Virotherapy for Colorectal Cancer.

Oncolytic adenoviruses (Ads) have potential applications in cancer therapy due to their ability to replicate and induce tumor cell death. However, their clinical application has been limited by the lack of efficient cell-based delivery systems that can provide protection from immune attack and prevent virus clearance by neutralizing antibodies. We previously demonstrated that menstrual blood-derived mesenchymal stem cells (MenSCs) can specifically target tumor cells and serve as a novel drug delivery platform. We engineered CRAd5/F11 chimeric oncolytic Ads that can infect MenSCs and preserve their tumor targeting ability in vitro. MenSCs loaded with these Ads were transplanted in a mouse tumor model. We found that a large number of the CRAd5/F11 viruses were accumulated in tumor site and mediated marked inhibitory effects against colorectal cancer (CRC). Thus, we concluded that MenSC-cloaked oncolytic Ads hold great potential as a novel virus-delivery platform for the therapy of various cancers, including CRC.

Upregulation of AKIP1 contributes to metastasis and progression and predicts poor prognosis of patients with colorectal cancer.

BACKGROUND: A kinase-interacting protein 1 (AKIP1) has been reported to play an important role in the development and progression of cancer. However, the clinicopathological and biological roles of AKIP1 in colorectal cancer (CRC) remain largely unknown. The aim of this study was to investigate AKIP1 protein expression in CRC and determine the correlation between AKIP1 protein expression and clinicopathological features, as well as prognosis in CRC patients. MATERIALS AND METHODS: AKIP1 protein expression was determined by immunohistochemical analysis using tissue microarrays of CRC. We also used an siRNA approach to knock down AKIP1 expression and determine the effect of AKIP1 on CRC cell migration by transwell analysis. RESULTS: AKIP1 expression in CRC tissue was significantly higher compared with that of noncancerous colorectal mucosa (P<0.001). Further analysis showed that AKIP1 expression was significantly associated with tumor diameter, TNM stage, and lymph node metastasis (P<0.05). Kaplan-Meier survival analysis demonstrated that patients with a positive AKIP1 expression had significantly poorer overall survival rates when compared with those with negative AKIP1 expression (P=0.031). Multivariate analysis using the Cox proportional hazard model, however, revealed that AKIP1 expression was not a significant independent prognostic factor for CRC. Transwell assay showed that the migration potential of si-AKIP1-transfected cells was significantly reduced when compared with control cells. CONCLUSION: Elevated AKIP1 expression may contribute to metastasis and progression of CRC. Moreover, high AKIP1 expression in CRC significantly correlated with a patient's shorter survival time. Therefore, AKIP1 may be a useful prognostic marker for CRC and a promising novel target for the treatment of CRC.