Low pneumoperitoneum pressure on venous thromboembolism in laparoscopic colorectal cancer surgery: A randomized controlled study.

INTRODUCTION: Venous thromboembolism (VTE) poses a significant risk in colorectal cancer surgeries due to hypercoagulability and the anatomical challenges of the pelvic cavity. With the advancement of minimally invasive techniques, intraoperative strategies for preventing VTE may prove to be effective. This study explores the effects of intraoperative pneumoperitoneum pressures on VTE incidence following colorectal cancer surgeries. METHODS: This single center parallel randomized controlled double-blind, trial involved 302 patients undergoing elective laparoscopic or robotic colorectal surgery. Patients were randomized to either a standard pneumoperitoneum pressure group (SP: 15 mmHg) or a low-pressure group (LP: 10 mmHg). Primary outcomes measured were the incidence of VTE, including symptomatic and asymptomatic DVT and PE. Secondary outcomes included postoperative D-dimer levels, surgery duration, blood loss, surgeon satisfaction, and oncological quality. RESULTS: Out of 302 randomized patients, 275 were evaluable post exclusions, with 138 in the SP group and 137 in the LP group. The incidence of VTE was 10.9 % in the SP and 13.9 % in the LP group, with no significant difference between the two (P = 0.450). Secondary outcomes such as D-dimer levels, surgery duration, and blood loss showed no significant differences between two groups. Surgeon satisfaction and oncological outcomes were similarly comparable. CONCLUSIONS: The trial demonstrated no significant difference in the incidence of VTE between standard and low pneumoperitoneum pressures. This suggests that lower pressures may not necessarily provide a benefit in reducing postoperative VTE in colorectal cancer surgeries.

Magnetic resonance imaging radiomics-based prediction of severe inflammatory response in locally advanced rectal cancer patients after neoadjuvant radiochemotherapy.

PURPOSE: To predict severe inflammatory response after neoadjuvant radiochemotherapy in locally advanced rectal cancer (RC) patients using magnetic resonance imaging (MRI) radiomics models. METHODS: This retrospective study included patients who underwent radical surgery for RC cancer after neoadjuvant radiochemotherapy between July 2017 and December 2019 at XXX Hospital. MRI radiomics features were extracted from T2WI images before (pre-nRCT-RF) and after (post-nRCT-RF) neoadjuvant radiochemotherapy, and the variation of radiomics features before and after neoadjuvant radiochemotherapy (delta-RF) were calculated. Eight, eight, and five most relevant features were identified for pre-nRCT-RF, post-nRCT-RF, and delta-RF, respectively. RESULTS: Eighty-six patients were included and randomized 3:1 to the training and test set (n = 65 and n = 21, respectively). The prediction model based on delta-RF had areas under the curve (AUCs) of 0.80 and 0.85 in the training and test set, respectively. A higher rate of difficult operations was observed in patients with severe inflammation (65.5% vs. 42.9%, P = 0.045). CONCLUSION: The prediction model based on MRI delta-RF may be a useful tool for predicting severe inflammatory response after neoadjuvant radiochemotherapy in locally advanced RC patients.

CircZFR promotes colorectal cancer progression via stabilizing BCLAF1 and regulating the miR-3127-5p/RTKN2 axis.

Aberrant expression of circular RNAs (circRNAs) is frequently linked to colorectal cancer (CRC). Here, we identified circZFR as a promising biomarker for CRC diagnosis and prognosis. CircZFR was upregulated in CRC tissues and serum exosomes and its level was linked to cancer incidence, advanced-stages, and metastasis. In both in vitro and in vivo settings, circZFR promoted the growth and spread while suppressing apoptosis of CRC. Exosomes with circZFR overexpression promoted the proliferation and migration of cocultured CRC cells. Mechanistically, epithelial splicing regulatory protein 1 (ESRP1) in CRC cells may enhance the production of circZFR. BCL2-associated transcription factor 1 (BCLAF1) bound to circZFR, which prevented its ubiquitinated degradation. Additionally, circZFR sponged miR-3127-5p to boost rhotekin 2 (RTKN2) expression. Our TCP1-CD-QDs nanocarrier was able to carry and deliver circZFR siRNA (si-circZFR) to the vasculature of CRC tissues and cells, which inhibited the growth of tumors in patient-derived xenograft (PDX) models. Taken together, our results show that circZFR is an oncogenic circRNA, which promotes the development and spread of CRC in a BCLAF1 and miR-3127-5p-dependent manner. CircZFR is a possible serum biopsy marker for the diagnosis and a desirable target for further treatment of CRC.

Relationship between MTHFR gene polymorphism and risk of thrombosis in postoperative patients with colorectal cancer.

An association between the methylenetetrahydrofolate reductase (MTHFR) C667T genotype and the risk of colorectal cancer, as well as a link between MTHFR gene polymorphism and thrombosis, have been revealed. However, the connection between MTHFR gene polymorphism and the risk of thrombosis in patients with colorectal cancer has remained to be fully elucidated. The present study investigated the link between MTHFR gene polymorphism and basic clinical data, postoperative D-dimer (DDi), postoperative thromboelastogram and postoperative thrombosis in 591 patients who underwent surgery for colorectal cancer. Postoperative DDi, thromboelastogram and postoperative thrombosis were not significantly different among patients with colorectal cancer and different MTHFR genotypes. While the results were 'negative', the present study may help physicians understand that it is not necessary to detect MTHFR polymorphism for therapeutic purposes. Regarding the danger of venous thrombosis, more focus should be placed on the standardized procedural enforcement system for deep vein thrombosis prevention for patients undergoing pelvic and abdominal surgery.

Construction and validation of a novel algorithm based on oncosis-related lncRNAs comprising the immune landscape and prediction of colorectal cancer prognosis.

Colorectal cancer (CRC) has high morbidity and mortality, particularly if diagnosed at an advanced stage. Although there have been several studies on CRC, few have investigated the relationship between oncosis and CRC. Thus, the purpose of the present study was to identify oncosis-related long noncoding RNAs (lncRNAs) and to establish a clinical prognostic model. Original data were acquired from The Cancer Genome Atlas database and PubMed. Differentially expressed oncosis-related lncRNAs (DEorlncRNAs) were identified and were subsequently formed into pairs. Next, a series of tests and analyses, including both univariate and multivariate analyses, as well as Lasso and Cox regression analyses, were performed to establish a receiver operating characteristic curve. A cut-off point was subsequently used to divide the samples into groups labelled as high- or low-risk. Thus, a model was established and evaluated in several dimensions. Six pairs of DEorlncRNAs associated with prognosis according to the algorithm were screened out and the CRC cases were divided into high- and low-risk groups. Significant differences between patients in the different risk groups were observed for several traits, including survival outcomes, clinical pathology characteristics, immune cell infiltration status and drug sensitivity. In addition, PCR and flow cytometry were performed to further verify the model. In summary, a new risk model algorithm based on six pairs of DEorlncRNAs in CRC, which does not require specific data regarding the level of gene expression, was established and validated. This algorithm may be used to predict patient prognosis, immune cell infiltration and drug sensitivity.

Erratum: Co-delivery of 5-fluorouracil and miRNA-34a mimics by host-guest self-assembly nanocarriers for efficacious targeted therapy in colorectal cancer patient-derived tumor xenografts: Erratum.

[This corrects the article DOI: 10.7150/thno.52076.].

Transanal Minimally Invasive Surgery for Rectal Anastomotic Stenosis After Colorectal Cancer Surgery.

BACKGROUND: Anastomotic stenosis is a common complication of colorectal cancer surgery with anastomosis. Transanal minimally invasive surgery is a novel approach to the treatment of anastomotic stenosis. OBJECTIVE: This study aimed to evaluate the efficacy and safety of transanal minimally invasive surgery for anastomotic stenosis treatment. DESIGN: This was a retrospective study. SETTINGS: This study was conducted at a comprehensive cancer center. PATIENTS: This study included patients with rectal anastomotic stenosis who after undergoing colorectal surgery were admitted to the Sir Run Run Shaw Hospital between September 2017 and June 2019. MAIN OUTCOME MEASURES: The primary outcome was the operative success rate. The secondary outcomes were intraoperative variables, postoperative complications, stoma closure conditions, and stenosis recurrence risks. RESULTS: Nine patients, aged 52 to 80 years, with a history of colorectal cancer with end-to-end anastomosis underwent transanal minimally invasive surgery for anastomotic stenosis. The distance between the stenosis and the anal verge ranged from 5 to 12 cm. The mean stenosis diameter was 0.3 cm. Four patients had completely obstructed rectal lumens. Eight of 9 patients successfully underwent transanal minimally invasive surgery radial incision and cutting. The average operation time was 50 minutes. After the procedure, 1 patient had symptomatic procedure-associated perforations but recovered with conservative treatment. No perioperative mortality occurred. One patient underwent transverse colostomy 1 month after transanal minimally invasive surgery because of proximal colon ischemia induced by primary rectal surgery. Eight patients underwent protective loop ileostomy. After transanal minimally invasive surgery, stoma closure was performed in 88% of patients with no stenosis recurrence or obstruction at follow-up (21-42 mo). LIMITATIONS: This study was limited by its small sample size and single-center design. CONCLUSIONS: Transanal minimally invasive surgery provides an excellent operative field, good maneuverability, and versatile instrumentation and is a safe and effective treatment for rectal anastomotic stenosis, especially for severe fibrotic stenosis or complete obstruction. See Dynamic Article Video at http://links.lww.com/DCR/B965 .

TIMP-2 regulates 5-Fu resistance via the ERK/MAPK signaling pathway in colorectal cancer.

5-Fluorouracil (5-Fu) is the first-line chemotherapeutic option for colorectal cancer. However, its efficacy is inhibited by drug resistance. Cytokines play an important role in tumor drug resistance, even though their mechanisms are largely unknown. Using a cytokine array, we established that tissue inhibitor metalloproteinase 2 (TIMP-2) is highly expressed in 5-Fu resistant colorectal cancer patients. Analysis of samples from 84 patients showed that elevated TIMP-2 expression levels in colorectal patients were correlated with poor prognostic outcomes. In a 5-Fu-resistant patient-derived xenograft (PDX) model, TIMP-2 was also found to be highly expressed. We established an autocrine mechanism through which elevated TIMP-2 protein levels sustained colorectal cancer cell resistance to 5-Fu by constitutively activating the ERK/MAPK signaling pathway. Inhibition of TIMP-2 using an anti-TIMP-2 antibody or ERK/MAPK inhibition by U0126 suppressed TIMP-2 mediated 5-Fu-resistance in CRC patients. In conclusion, a novel TIMP-2-ERK/MAPK mediated 5-Fu resistance mechanism is involved in colorectal cancer. Therefore, targeting TIMP-2 or ERK/MAPK may provide a new strategy to overcome 5-Fu resistance in colorectal cancer chemotherapy.

Primary colonic lymphoma: report of two cases and a literature review.

Primary colonic lymphoma is a very rare malignant tumor with no standard treatment. We report two cases of primary colonic lymphoma successfully treated with surgery and chemotherapy, and chemotherapy alone, respectively. The first case was a 61-year-old woman who presented with abdominal pain of more than 1 month. The patient was diagnosed with a colonic tumor, and immunohistochemical examinations confirmed the initial diagnosis of colonic lymphoma. The patient underwent laparoscopic-assisted right hemicolectomy followed by postoperative adjuvant chemotherapy with the cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen, combined with targeted therapy with rituximab (R-CHOP). The second case was a 78-year-old man who presented with a complaint of abdominal distention for more than 1 year. Diffuse large B-cell lymphoma was definitively diagnosed by immunohistochemical examinations, and the patient underwent systemic chemotherapy with the R-CHOP regimen. Primary colonic lymphoma is a rare type of non-Hodgkin's lymphoma (NHL), and the clinical treatment is not standardized, unlike for many other types of lymphoma. Therefore, treatment is mainly based on the patient's symptoms to determine whether surgery or systemic chemotherapy is appropriate. Rituximab is effective in some patients and may play an important role in the treatment of unresectable or asymptomatic colonic lymphoma.

[Corrigendum] LYPD8 regulates the proliferation and migration of colorectal cancer cells through inhibiting the secretion of IL­6 and TNF­α.

Following the publication of the above paper, the authors realized that, in their follow­up experiments, the STAT3 and p65 antibodies they used had already expired prior to the results being published. This affected the confidence that the authors could place in the results published in Figs. 1 and 3E. In addition, the findings were also inconsistent with Fig. 4A and B, potentially causing confusion for the readers. The authors therefore repeated some of these experiments with newly purchased antibodies; they also changed the RT-qPCR results. In the published manuscript, the authors investigated the expression of LYPD8 mRNA expression in tissues from stages I, II, and III whereas in the revised manuscript they have investigated stages II and IV. In addition, the authors have supplemented the manuscript with new transwell assays. The revised figures are presented on the next two pages (Figs 1-4). Repeating these particular experiments has resulted in the following changes being necessary to the text of the published paper (changes are highlighted in bold): i) The fourth sentence in the Abstract, on p. 2389, should read as follows: "The results revealed that the expression of LYPD8 was significantly reduced in the CRC tissue compared with that in precancerous tissue and normal tissue, particularly in stage IV tissue." ('III' has been changed to 'IV'). ii) In the Materials and methods section, "Histological analysis" subsection on p. 2390, the last three sentences should be replaced with the following text: "The histological sections were then stained with the DAB Kit (cat. no. PV­9000; ZSGB­BIO, Beijing, China). All sections were observed under a bright­field microscope (Nikon Corporation, Tokyo, Japan)." iii) In the "Cell culture" subsection in the right­hand column, the first four sentences should be revised to the following: "Four CRC cell lines (SW480, SW620, HCT116 and RKO) were used. SW480 (ATCC® CCL­228™, organism, human; tissue, colon; disease, colorectal adenocarcinoma), SW620 (ATCC® CCL­227™, organism, human; tissue, colon; derived from metastatic site, lymph node; disease, colorectal adenocarcinoma), HCT116 (ATCC® CCL­247™, organism, human; tissue, colon; disease, colorectal carcinoma) and RKO (ATCC® CRL­2577™, organism, human; tissue, colon; disease, carcinoma) cells were purchased from the American Type Culture Collection (Manassas, VA, USA). The four cell lines within passages 10 were used in all experiments, and the cell lines were maintained at 37˚C in a humidified incubator containing 5% CO2". Also, in line 8 of p. 2391, the cell lines here should be changed to "SW480, SW620 and HCT116 cells", and on line 11, "HT29 cells" should be changed to "RKO cells". iv) In the Results section, the following changes to the text are necessary: In the "Correlation of the expression of LYPD8 with STAT3/P65 phosphorylation and IL­6/TNF­α secretion in patients with CRC" subsection, in the second sentence, "immunofluorescence" should have been written as "immunohistochemistry", and the fourth sentence should have read as follows: "The results of the western blotting showed that the levels of p­P65/P65 and p­STAT3/STAT3 gradually increased between stage II and IV (Fig. 1B and C)." Then, the three sentences starting on line 7 on p. 2391 should now read as follows: "Following this, the gene expression levels of LYWPD8 in stage II and IV CRC tissue, precancerous tissue, and normal tissue were assessed using RT­qPCR analysis (Fig. 2C). Compared with the precancerous tissue and normal tissue, the gene expression of LYPD8 was significantly reduced in stage II and IV tissues. Furthermore, the expression of LYPD8 was reduced in stage IV tissue compared with that in stage II tissue." v) In the subsequent subsection, "Construction and overexpression of LYPD8 in CRC cells", the first sentence should have read as follows: "The plasmid DNA for overexpressing LYPD8 was constructed using the eukaryotic expression vector (pIRES2), as shown in Fig. 3A and B, and the relative expression levels of LYPD8 in the RTO, SW480 HCT116 and SW620 cells were examined by RT-qPCR analysis. vi) In the "Overexpression of LYPD8 inhibits CRC cell proliferation and migration" subsection, the penultimate sentence as it appears towards the foot of p. 2392 should now read as follows: "As shown in Fig. 4C and D, a more marked inhibitory effect on cell migration was observed in the LYPD8 OE group compared with that in the control, LYPD8 OE + IL­6 and LYPD8 OE + TNF­α groups." vi) In the Discussion, the sentence starting on p. 2394, right­hand column, line 10 should read as follows: "By contrast, the expression of LYPD8 was significantly reduced in stage II and IV CRC tissues." vii) Finally, some revisions were necessary to the descriptions in the figure legends for Figs. 1, 2 and 4, as follows (only the affected text is included, and the changes are indicated in bold): Figure 1. STAT3 and P65 are activated in colonic tumor tissues from patients. (A) Representative immunohistochemistry images revealing activated STAT3 and P65 in colonic cancer tissue and precancerous tissue. Scale bar, 100 µm. (B) Representative western blotting revealing the expression of p­P65, P65, p­STAT3 and STAT3 in stages II and IV colonic tumor tissues. GAPDH was used as a control. (C) Band intensities of western blotting for p­P65/P65 and p­STAT3/STAT3 in stage II and IV tissues were analyzed. The data are reported as the mean ± standard deviation of experiments (n=4). **P<0.05, phosphorylation levels of STAT3 in stage II tissues vs. in stage IV tissues. Figure 2. Association between IL­6/TNF­α and the expression of LYPD8 in colonic tumor tissue, precancerous tissue and normal tissue at different stages. (A) IL­6 and (B) TNF­α secretion were analyzed by ELISA in stage II and IV colonic tumor tissue and precancerous tissue. (C) Gene expression of LYPD8 in stage II and IV colonic tumor tissue and precancerous tissue. ß­actin was used as a control. The data are reported as the mean ± standard deviation of experiments (n=6). **P<0.01, LYPD8 mRNA expression of normal tissue, precancerous tissue vs. colonic tumor tissue in stage II and IV tissues. Figure 4. Effects of the overexpression of LYPD8 on SW480 cell proliferation and migration. (A) Cell viability of the Control, LYPD, LYPD8 OE + IL­6 and LYPD8 OE + TNF­α groups of SW480 cells. (B) SW480 cells were treated with different concentrations (0.5, 1 and 2 µM) of niclosamide and different concentrations (5, 15 and 30 µM) of JSH­23, respectively. (C) Numbers of migratory SW480 cells from the Control, LYPD8, LYPD8 OE + IL­6 and LYPD8 OE + TNF­α groups. (D) Transwell assay of SW480 cells from the (a) Control, (b) LYPD8 OE, (c) LYPD8 OE + IL­6 and (d) LYPD8 OE + TNF­α groups (magnification, ×200).  Note that the replacement of the original figures and these revisions made to the text do not drastically alter the overall conclusions reported in the study. The authors are very grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum; furthermore, they apologize for any inconvenience caused to the readership of the Journal. [the original articles was published in Oncology Reports 41: 2389­2395, 2019; DOI: 10.3892/or.2019.7034].

Co-delivery of 5-fluorouracil and miRNA-34a mimics by host-guest self-assembly nanocarriers for efficacious targeted therapy in colorectal cancer patient-derived tumor xenografts.

Rationale: A co-delivery system that can transport chemotherapeutic drugs and nucleotide drugs to distinct targets in tumors is an attractive strategy for cancer therapy. In this study, well-defined targeted quantum dot (QD)-based multifunctional nanocarriers were developed through self-assembly driven by host-guest interactions. 5-fluorouracil (5-FU) and microRNA-34a mimics (miR-34a(m)) were co-administered to achieve synergistic effects for colorectal cancer (CRC) therapy for the first time. Furthermore, the CRC patient-derived tumor xenograft (PDX) model, which closely mimics human CRC tumor pathological properties, was used for evaluating the therapeutic effect in this research. Methods: Multiple ß-cyclodextrin (CD)-attached QD nanoparticles were used as host molecules. An adamantane (ADA)-modified TCP1 peptide-targeting ligand (TCP1) was used as the guest molecule. 5-FU and miR-34a(m) were loaded into TCP1-CD-QD nanocarriers, which were used to treat CRC in vitro and in vivo. In addition, the CRC PDX model was used to evaluate the treatment efficacy of this co-delivery system. Results: 5-FU and miR-34a(m) can be efficiently encapsulated into TCP1-CD-QD nanocarriers and delivered into CRC cells, which led to the inhibition of the proliferation and migration of CRC cells in vitro and suppression of tumor growth in a CRC cell-derived tumor xenograft model. The obtained data further suggested that co-delivery of 5-FU and miR-34a(m) could achieve synergistic effects for CRC therapy. Notably, targeted therapy via the co-delivery of 5-FU and miR-34a(m) by TCP1-CD-QD nanocarriers significantly inhibited the growth of PDX tumors. Conclusions: These studies strongly indicate that such a nanocarrier-based co-delivery system is a promising combined therapeutic strategy that utilizes chemotherapeutic drugs and nucleotide drugs for enhancing colorectal cancer targeting and synergistic therapy.

Low-residue versus clear liquid diet before colonoscopy: An updated meta-analysis of randomized, controlled trials.

Great value in the early identification and treatment of adenomatous polyps or early canceration using colonoscopy has been recognized. A clear colonoscopic vision brought by good intestinal preparation will become crucial. Several studies have completed using the low-residue diet (LRD) versus a clear liquid diet (CLD) the day before colonoscopy that presenting contradictory results. Therefore, a more comprehensive and updated meta-analysis is needed to summarize the findings on the effects of LRD and CLD on intestinal preparation and the quality of coloscopy.The comprehensive search was performed in PubMed/MEDLINE, Scopus, Cochrane databases (February 2020). LRD vs CLD before colonoscopy were included in this study. Mantel-Haenszel or DerSimonian and Laird models with the relative risk (RR) to evaluate differences in intestinal preparation, tolerance, readiness to repeat preparation, detected of a polyp, and overall adverse reactions.Total 16 studies (N = 3413) were eligible. Patients with LRD compared with CLD indicated significantly better of tolerability (RR 0.92;95% CI,0.85-0.99; P < .05) and willingness to repeat intestinal preparation (RR 0.86; 95% CI 0.79-0.93; P < .05), but no differences with adequate intestinal preparations, detected polyp or overall adverse reactions (all P > .05).Patients with LRD the day before colonoscopy show better tolerance and willingness to repeat intestinal preparation, and no difference with adequate intestinal preparations compared with CLD, but the recommended level of evidence is weak. However, in terms of the detection rate of intestinal adenomas, the LRD group is not weaker than the CLD group, for its evidence level is high, and can significantly reduce the hunger experience of patients.

Unmasking carcinoma-associated fibroblasts: Key transformation player within the tumor microenvironment.

Fibroblasts have gained increasing attention in tissue desmoplasia, especially in tumors. Activated fibroblasts from various sources modulate matrix composition and stiffness associated with organ fibrosis as well as tumor progression. More importantly, cancer-associated fibroblasts (CAFs) interacts with both cancer cells and other stromal cells, providing a tumor-promoting microenvironment for tumor invasion and metastasis. However, CAF biology is not fully understood due to its heterogeneity. Here, we describe the main transforming cues that contribute to CAF activation and unveil the expanding CAF heterogeneity associated with tumor progression in multiple aspects. Finally, we summarize the prospective promising and challenging stroma-targeted anti-tumor strategies.

CXCL-13 Regulates Resistance to 5-Fluorouracil in Colorectal Cancer.

PURPOSE: 5-Fluorouracil (5-Fu) is used as a conventional chemotherapy drug in chemotherapy for patients with advanced colorectal cancer, but many patients still suffer from treatment failure due to 5-Fu resistance. Emerging observations revealed the important role of chemokine (C-X-C motif) ligand 13 (CXCL-13) in tumor microenvironment and its relationship with prognosis in patients with colorectal cancer. This study is designed to reveal the important role of CXCL-13 in causing colorectal cancer resistance to 5-Fu. MATERIALS AND METHODS: CXCL-13 levels of patient's serum or cell culture supernatants were measured separately by enzyme-linked immunosorbent assay. In cell assays, cell viability is detected by Cell Counting Kit-8. Therefore, the recombinant human CXCL-13 was used to simulate its high expression in cells while its antibody and siRNA were used to reduce CXCL-13 expression in cells. RESULTS: In this study, we demonstrated that CXCL-13 is associated with 5-Fu resistance by culture medium exchange experiments and cytokine arrays of colorectal cancer resistant and nonresistant cells. Clinical studies showed that CXCL-13 is highly expressed in the serum of 5-Fu-resistant patients. High levels of serum CXCL-13 also predict a worse clinical outcome. The addition of recombinant CXCL-13 cytokine resulted in 5-Fu resistance, while its antibody overcame 5-Fu resistance, and knockdown of CXCL-13 expression by siRNA also reduced 5-Fu resistance, which can be saved by added recombination CXCL-13. CONCLUSION: These results not only identify a CXCL-13 mediated 5-Fu resistance mechanism but also provide a novel target for 5-Fu-resistant colorectal cancer in prevention and treatment strategies.

A novel scoring system predicting survival benefits of palliative primary tumor resection for patients with unresectable metastatic colorectal cancer: A retrospective cohort study protocol.

The role of palliative primary tumor resection (PPTR) in improving survival in patients with synchronous unresectable metastatic colorectal cancer (mCRC) is controversial. In this study, we aimed to evaluate whether our novel scoring system could predict survival benefits of PPTR in mCRC patients.In this retrospective cohort study consecutive patients with synchronous mCRC and unresectable metastases admitted to Sir Run Run Shaw Hospital between January 2005 and December 2013 were identified. A scoring system was established by the serum levels of carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9), neutrophil/lymphocyte ratio (NLR), and lactate dehydrogenase (LDH). Patients with scores of 0, 1-2, or 3-4 were considered as being in the low, intermediate, and high score group, respectively. Primary outcome was overall survival (OS).A total of 138 eligible patients were included in the analysis, of whom 103 patients had undergone PPTR and 35 had not. The median OS of the PPTR group was better than that of the Non-PPTR group, with 26.2 and 18.9 months, respectively (P < .01). However, the subgroup of PPTR with a high score (3-4) showed no OS benefit (13.3 months) compared with that of the Non-PPTR group (18.9 months, P = .11). The subgroup of PPTR with a low score (52.1 months) or intermediate score (26.2 months) had better OS than that of the Non-PPTR group (P < .001, P = .017, respectively).A novel scoring system composed of CEA, CA19-9, NLR, and LDH values is a feasible method to evaluate whether mCRC patients would benefit from PPTR. It might guide clinical decision making in selecting patients with unresectable mCRC for primary tumor resection.

Serum chitinase activity prognosticates metastasis of colorectal cancer.

BACKGROUND: This study aimed to evaluate the value of chitinase activity in prognosticating the occurrence of metastasis in and prognosis of patients with colorectal cancer (CRC). METHODS: The chitinase activity in four different groups, namely 335 CRC patients without distant metastasis at their first visit (Group 1), 51 patients with CRC having synchronous liver metastasis (Group 2), 100 healthy age-matched controls (Group 3) and 40 patients with liver cancer (Group 4), were assayed using an enzyme-linked immunosorbent assay. The Cox proportional hazards ratio model and Kaplan-Meier curve were used to identify the association between chitinase activity and the clinical outcome of CRC patients without metastasis in the training set and testing set at their first visit. An in vitro Transwell experiment was performed to evaluate the migration of colon cancer cells. RESULTS: Patients with high chitinase activity had a significantly higher metastasis risk than those with low chitinase activity in the training and testing sets during follow-up, both at stage I/II and stage III. Further, multivariate analysis revealed that chitinase activity was an independent risk factor prognosticating liver metastases (P = 0.001). The combination of chitinase activity and lymph node metastasis status increased the accuracy of the prognosis of liver metastases after radical resection (P = 0.454E-011). In addition, chitinase promoted CRC cell migration in vitro. CONCLUSIONS: Chitinase activity can prognosticate the occurrence of metastasis in patients with CRC. Moreover, the combination of chitinase activity and N stage increased the power of prognosticating the occurrence of metastasis. Inhibiting chitinase activity may serve as a new strategy to treat metastases of CRC.

LYPD8 regulates the proliferation and migration of colorectal cancer cells through inhibiting the secretion of IL­6 and TNF­α.

Ly6/Plaur domain­containing 8 (LYPD8) contributes to the segregation of intestinal microbiota and intestinal epithelia and is critical for the prevention of intestinal inflammation. However, its relevance in cancer biology remains to be fully elucidated. The present study aimed to clarify the biological effects of LYPD8 on colon cancer tissue from patients and colorectal cancer (CRC) cells. The results revealed that the expression of LYPD8 was significantly reduced in the CRC tissue compared with that in precancerous tissue and normal tissue, particularly in stage III tissue. The results also revealed increased levels of P65 and signal transducer and activator of transcription 3 (STAT3) phosphorylation and increased secretion of interleukin­6 (IL­6) and tumor necrosis factor­α (TNF­α) in CRC tissue compared with levels in precancerous tissue. Supporting these findings, the levels of secreted TNF­α and IL­6 were significantly reduced when LYPD8 was overexpressed in human CRC cells, and the secretion of TNF­α and IL­6 were positively associated with the phosphorylation of STAT3 and P65. However, this trend was restored upon supplementation with TNF­α and IL­6 in CRC cells. Furthermore, the overexpression of LYPD8 in CRC cells significantly inhibited CRC cell proliferation and migration. Overall, the LYPD8­mediated tumor­inhibiting role involves a direct effect on the secretion of IL­6/TNF­α in CRC cells by reducing the phosphorylation of STAT3 and P65.

Relationship between exposure to PM2.5 and lung cancer incidence and mortality: A meta-analysis.

We conducted a meta-analysis to examinine the relationship between exposure to PM2.5 and lung cancer incidence and mortality. In total, 17 studies met our inclusion criteria and provided information necessary to estimate the change in lung cancer risk per 10 µg/m3 increase in exposure to PM2.5. The random-effects model was used to estimate the relative risk (RR) for specific PM2.5 values. The meta-estimate for lung cancer risk associated with PM2.5 was 1.11 for mortality (95% CI: 1.05, 1.18) and 1.08 (95% CI: 1.03, 1.12) for incidence. Analyses by continent showed that the meta-estimate for lung cancer mortality associated with PM2.5 was greatest in North America [1.15 (95% CI: 1.07, 1.24)], followed by Asia [1.12 (95% CI: 0.94, 1.35)], and then Europe [1.05 (95% CI: 1.01, 1.10)]. Lung cancer incidence associated with PM2.5 was greatest in Asia [1.09 (95% CI: 1.03, 1.15)], followed by North America [1.06 (95% CI: 1.01, 1.11)], and then Europe [1.03 (95% CI: 0.61, 1.75)]. In subgroup analyses of country, the mortality meta-estimate for developed countries was 1.14 (95% CI: 1.06, 1.23), and for developing countries was 1.03 (95% CI: 1.00, 1.07). The incidence meta-estimate for developed countries was 1.07 (95% CI: 0.96, 1.20), and was similar to that of developing countries, 1.07 (95% CI: 1.06, 1.09). In subgroup analyses of males and females, the meta-estimate for lung cancer mortality associated with PM2.5 was greater for males [1.26 (95% CI: 1.15, 1.40)] than for females [1.17 (95% CI: 0.98, 1.39)]. The meta-estimate for lung cancer incidence associated with PM2.5 was greater for males [1.23 (95% CI: 0.83, 1.81)] than for females [1.15 (95% CI: 1.12, 1.18)]. In subgroup analyses of smoking status, the meta-estimate for lung cancer mortality associated with PM2.5 for former smokers was 1.46 (95% CI: 0.84, 2.55), for current smokers was 1.33 (95% CI: 1.20, 1.49), and for never smokers was 1.16 (95% CI: 1.02, 1.33), respectively. The meta-estimate for lung cancer incidence associated with PM2.5 for former smokers was 1.19 (95% CI: 0.95, 1.50), for never smokers was 1.10 (95% CI: 0.76, 1.59), and for current smokers was 1.03 (95% CI: 0.87, 1.21). The relative risks of a relationship between PM2.5 and lung cancer incidence and mortality were 1.08 (95% CI: 1.03, 1.12) and 1.11 (95% CI: 1.05, 1.18), respectively. These findings will provide some evidence for policy makers and public health practitioners worldwide.

Human cytomegalovirus infection and colorectal cancer risk: a meta-analysis.

Human cytomegalovirus infection (HCMV) has been recently considered as a factor for tumorigenesis. The current study used meta-analytical techniques to explore the prevalence of HCMV in tumor tissues and the relationship between human cytomegalovirus and colorectal cancer (CRC) risk. 11 studies detecting HCMV DNA in tumor tissues were included in meta-analysis. The prevalence rate and odds ratio (OR) were two main parameters. The overall prevalence of human cytomegalovirus DNA in tumor tissues were 27.5% (95% CI = 17.2%-37.8%). Binary logistic regression showed that the studies reported before 2010 involving formalin-fixed specimens from patients in developed region represented a lower proportion of HCMV. The tumor tissues had a significantly higher rate of virus infection compared with normal tissues (OR = 6.59, 95% CI = 4.48-9.69, I2 = 0%, P = 0.71). Subgroup analysis revealed the prevalence of the virus didn't differ in patients with different tumor stages, in tumor cells with different histologic grades, also in different kinds of specimen (polyp and adenocarcinoma). The results of current study suggested a statistically association between the virus infection and an increased risk of colorectal cancer.

The prognostic value of CSCs biomarker CD133 in NSCLC: a meta-analysis.

The prognostic value of cancer stem cells (CSCs) marker CD133 in non-small-cell lung cancer (NSCLC) remains controversial. We performed this meta-analysis of 32 eligible studies to clarify the prognostic value of CD133 and provide evidence for CSCs hypothesis. We calculated pooled hazard ratio (HR) for survival outcomes and pooled odds ratio (OR) for clinical parameters associated with CD133 in total 3595 NSCLC patients by STATA. Our results showed that NSCLC patients with higher CD133 expression had shorter overall survival time only in Asian patients (HR = 3.80, 95% CI: 3.12-4.04, p < 0.001; I2 = 32%) but not in Caucasian patients (HR = 1.15, 95% CI: 0.88-1.52, p = 0.307; I2 = 0%), suggesting that differential prognostic value of CD133 in distinct ethnic group. We speculated that the intrinsic EGFR gene status of CSCs might be responsible for this racial difference. Additionally, we found that higher expression of CD133 was associated with poor differentiation (OR = 2.03, 95% CI: 1.32-3.14, p = 0.001) and lymph node metastasis (OR = 2.39, 95% CI: 1.62-3.52, p < 0.001) but there was no significant difference of CD133 expression between adenocarcinoma and squamous carcinoma (OR = 1.13, 95% CI: 0.93-1.38, p = 0.3) in NSCLC patients. These results may provide a new therapeutic perspective on the treatment of NSCLC patients according to the expression of CD133 in distinct ethnic group.