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The number of lymph node metastasis (LNM) is a strong prognostic factor in the treatment of colorectal cancer (CRC). However, the impact of the mesentery location on LNM remains unclear. We assessed the impact LNM location on the recurrence of stage III CRC.Subjects with CRC and pathologically positive LNM were enrolled retrospectively. We defined three groups: LNM adjacent to the tumour (group A), metastases with horizontal or vertical spread (group B), and metastases with both horizontal and vertical spread (group C). Recurrence-free survival (RFS) was the primary outcome measure used for the study.A total of 241 (Group A: 121, B: 90, and C: 30) patients were recruited for the study. Multivariate analysis by Cox regression model indicated LNM location to be an independent predisposing risk factor for recurrence [group B: Hazard ratio (HR) 2.01, 95% Confidential interval (CI) 1.12-3.60, P = 0.019; group C: HR 3.00, 95% CI 1.34-6.72, P = 0.008]. Addition of mesentery spread to the N classification was significant risk factor for recurrence (mN2a: HR 2.01, 95% CI 1.07-3.78, P = 0.029; mN2b: HR 3.96, 95% CI 2.12-7.40, P 0.01). Comparison of Harrell's C-index values was conducted, and the modified N staging risk was 0.6377, whereas the TNM N stage classification was 0.5869.Mesentery location of LNM was a risk factor and consideration of it might be beneficial for accurate prediction of CRC prognosis.

Metformin has been reported to be associated with improved cancer prognosis when used in combination with chemotherapy and/or radiotherapy. In this study, we present a systematic review and meta-analyses of studies evaluating the association of tumor pathological response with the use of metformin during neoadjuvant chemoradiotherapy (NACRT) in rectal and esophageal/gastroesophageal cancer patients.We systematically searched databases for articles that compared concurrent metformin use with no metformin use in cancer patients treated with NACRT following the PRISMA 2020. The design and quality of the collected studies were reviewed, and meta-analyses were performed on the pathologic complete response (pCR) rate, tumor regression grade (TRG), T factor downstaging, and N factor downstaging.Three databases were searched, and 220 papers were screened. Five retrospective cohort study papers were eligible for the meta-analysis, with a total of 2041 patients. The included papers contained only rectal and esophageal/gastroesophageal cancers. In the metformin group, the pCR rate was 26% [20-32%], and metformin was associated with the pCR rate (odds ratio [OR] = 0.51 [0.34-0.76], p 0.01). Meta-regression analysis of the pCR rate showed a positive correlation with adenocarcinoma (coefficient = 0.13 [0.02-0.25], p = 0.03) and fluoropyrimidine anticancer drug use (coefficient = 0.01 [0.001-0.02], p = 0.03).The results suggest that metformin is associated with pCR rate when used in combination with NACRT. The association of metformin and pCR rate in combination with fluoropyrimidine anticancer drugs was observed mostly for adenocarcinoma patients.

Objective The relationship between preoperative mean corpuscular volume and postoperative prognosis has been reported in some cancers recently, but no certain consensus has been reached, especially for colorectal cancer. We evaluated the usefulness of mean corpuscular volume as a prognostic factor in colorectal cancer patients. Methods This study included 1003 patients with colorectal cancer who underwent curative surgery in a single institution. The relationship between mean corpuscular volume values and postoperative recurrence was evaluated by fractional polynomial model. Based on the result, patients were divided into groups according to mean corpuscular volume values. Clinicopathological factors and long-term outcomes were compared between the groups. Results The risk of postoperative recurrence according to mean corpuscular volume value showed a J-shaped curve, suggesting that both low and high mean corpuscular volume have high risk. Low mean corpuscular volume (≤84 fl) group was oncologically advanced in terms of pathological tumor stage, histological grade and lymphatic invasion with higher inflammation markers. High mean corpuscular volume (>95 fl) group had higher frequency of drinking habit with higher values of aspartate aminotransferase, alanine aminotransferase and γ-glutamyl transpeptidase. Abnormal mean corpuscular volume group including these two groups showed significantly worse disease-free survival than the other (P < 0.001). Multivariate analysis suggested that abnormal mean corpuscular volume was an independent risk factor for postoperative recurrence (hazard ratio, 1.344; 95% confidence interval, 1.005–1.796; P = 0.046). Furthermore, its prognostic impact was more significant in pStage III than in other stages. Conclusion Preoperative low and high mean corpuscular volume is a poor prognostic factor in colorectal cancer patients. It could be a predictive marker to estimate worse survival outcome after surgery.

The aim of this study was to evaluate the effect of biologics on the risk of advanced-stage inflammatory bowel disease (IBD)-associated intestinal cancer from a nationwide multicenter data set.The medical records of patients with Crohn's disease (CD) and ulcerative colitis (UC) diagnosed with IBD-associated intestinal neoplasia (dysplasia or cancer) from 1983 to 2020 were included in this study. Therapeutic agents were classified into 3 types: biologics, 5-aminosalicylic acid, and immunomodulators. The pathological cancer stage was compared based on the drug used in both patients with CD and UC.In total, 1,042 patients (214 CD and 828 UC patients) were included. None of the drugs were significantly associated with cancer stage in the patients with CD. In the patients with UC, an advanced cancer stage was significantly associated with less use of biologics (early stage: 7.7% vs advanced stage: 2.0%, P0.001), 5-aminosalicylic acid, and immunomodulators. Biologic use was associated with a lower incidence of advanced-stage cancer in patients diagnosed by regular surveillance (biologics [-] 24.5% vs. [+] 9.1%, P = 0.043), but this was not the case for the other drugs. Multivariate analysis showed that biologic use was significantly associated with a lower risk of advanced-stage disease (odds ratio = 0.111 [95% CI, 0.034-0.356], P0.001).Biologic use was associated with a lower risk of advanced IBD-associated cancer in patients with UC but not with CD. The mechanism of cancer progression between UC and CD may be different and needs to be further investigated.

Background/aim The role of brahma-related gene 1 (BRG1)-associated factor 57 (BAF57), a transcription factor, has been determined in prostate, breast, and ovarian cancer. However, the relationship between BAF57 and colorectal cancer (CRC) is obscure. Thus, we examined the functional correlation between BAF57 expression and oncological malignancy in CRC in vitro. Materials and methods BAF57 expression in WiDr and HT29 CRC cell lines and clinical specimens from CRC patients was analysed by western blotting and/or RT-PCR. BAF57 expression was down-regulated in WiDr cells through siRNA transfection. An invasion assay was also performed to assess malignancy. Results BAF57 was expressed in both human CRC cell lines. Overall survival and recurrence-free survival rates were significantly reduced in high BAF57-expressing specimens. BAF57 expression was an independent predictive factor for long-term survival. Conclusion BAF57 correlates with oncological malignancy and may be a novel therapeutic target in CRC.

Risk stratification is required to improve the management of pouchitis with ulcerative colitis (UC) patients who undergo ileal pouch-anal anastomosis (IPAA). Recently, the colectomy risk score (CRS) has been used to assess UC severity and predict the need for surgery. We explored whether the CRS predicted pouchitis in patients with UC who underwent IPAA. This retrospective study included 168 UC patients who underwent IPAA. Pouchitis was diagnosed according to the pouchitis disease activity index. The primary endpoint was the cumulative incidence of pouchitis. The risk factors for pouchitis using preoperatively obtained data, including the CRS, were investigated. Based on their CRS, patients were assigned to low- (scores 0-3), intermediate- (scores 4-6), and high-risk (scores 7-9) groups. The incidence of pouchitis was estimated using the Kaplan-Meier curve. CRS validity was assessed using the Cox proportional hazards model. During the median 7.2 (interquartile range [IQR] 2.8-11.1) years' follow-up, 37 (28.5%) patients were diagnosed with pouchitis. Patients with pouchitis had significantly higher CRS than patients without pouchitis (median 7.0; IQR, 4.0-7.0 vs median 5.0; IQR, 3.0-7.0). The cumulative incidences of pouchitis in the low-, intermediate-, and high-risk groups were 10.3%, 18.3%, and 36.1% at 5 years, respectively. Thus, the incidence trended to increase significantly as CRS increased. Multivariate analysis revealed high-risk CRS status was an independent predictor of pouchitis (hazard ratio: 18.03; 95% confidence interval 1.55-210.05). CRS is useful in risk stratification for the development of subsequent pouchitis in patients with UC undergoing IPAA.

Background It has been reported that in conventional open surgery, approximately 10% of surgical gloves are perforated during surgery without being noticed. To protect both the patient and medical staff from harm, double gloving or changing gloves routinely at certain intervals during surgery is recommended. However, whether these protective measures are also necessary for laparoscopic colorectal surgery is unknown because the actual perforation rate during laparoscopic procedures is unclear. Methods Seventy-seven laparoscopic colorectal surgeries were evaluated, and a total of 616 surgical gloves used in the surgeries were collected for analysis. The presence of glove perforation was tested by the standard water-leak test method (EN455-1). Results Seven perforations were detected (1.1%). The duration of the laparoscopic procedure was not a statistically significant risk factor for glove perforation (p = 0.41). Postoperative surgical site infections (SSIs) were observed in 12 cases (15.6%), but there was no significant correlation between the presence of glove perforation and SSI (p = 0.92). According to the bacterial cultivation results, the majority of causative agents of SSI were enterobacteria, which belong to the major gut flora. Conclusion Although the perforation rate was considerably lower than that in open surgery, surgical glove perforation occurred during laparoscopic procedures. Double gloving in laparoscopic colorectal surgery is recommended not to prevent SSI but to protect medical workers from harmful infections after direct contact with the patient.

In laparoscopic surgery (LS) for colorectal cancer (CRC), the relationship between intraoperative end-tidal carbon dioxide concentration (EtCO2) and surgery-related complications remains unexplored. This study assessed the impact of intraoperative EtCO2 on postoperative complications in LS for CRC. In total, 909 patients who underwent LS for CRC were enrolled. Hypocapnia and hypercapnia were defined as EtCO2 40 mmHg, respectively, and the relationships between hypocapnia or hypercapnia duration and postoperative complications were analyzed. The median (range) durations of hypocapnia and hypercapnia were 2.0 (0–8.3) h and 0.3 (0–5.8) h, respectively. Complications were observed in 208 cases (23.0%), which included 37 (4.1%) instances of anastomotic leakage and 86 (9.5%) of superficial surgical site infection (SSI). While the hypercapnia duration was not associated with the short-term outcomes, prolonged hypocapnia was significantly correlated with complications (p = 0.02), specifically superficial SSI (p = 0.005). Multivariate analyses adjusted for confounding factors confirmed that hypocapnia prolongation was an independent risk factor for postoperative superficial SSI [OR 1.19; 95% confidence interval (Cl) 1.03–1.36, p = 0.01]. Intraoperative hypocapnia may be a risk factor for postoperative complications, in particular superficial SSI, in LS for CRC.

Obesity is a risk factor for colorectal cancer (CRC), and the intestinal microbiome is considered to contribute to CRC and obesity. Nonetheless, the role of the intestinal microbiome in obesity-related CRC is unclear. This study aimed to clarify the relationship between obesity-related CRC and the intestinal microbiome using a mouse model.We compared an obese and insulin-resistant type 2 diabetes mouse model [KKAy] to wild-type mice (WT) [C57BL/6 J]. Azoxymethane was intraperitoneally injected to develop a mouse model CRC. At 26 weeks, we compared the number of tumors and the intestinal microbiome. We also compared them across two models, namely, antibiotic cocktail and co-housing.In all models, KKAy mice had a significantly greater number of tumors than WT mice. Analysis showed that the distribution of the intestinal microbiome changed in both models; however, no difference in tumor development was observed. Tumor expression was suppressed only in the antibiotic cocktail model of WT, whereas KKAy mice bore tumors (C57Bl/6 J: KKAy, 0/9:8/8; p 0.001). KKAy mice remained predominantly tumor-bearing in all treatments.Based on the results, the intestinal microbiome may not be associated with tumorigenesis in obesity-related CRC. It may be necessary to think of other facts linked to obesity-related CRC.

STAT3 is involved in the progression of several cancers, and has been proposed as target for therapy. Indeed, the multitargeted tyrosine kinase inhibitor drug regorafenib, which indirectly inhibits STAT3, can significantly enhance the effects of anti-programmed death receptor (PD)-1 therapy in hepatocellular carcinoma (HCC) models. Here, we studied the impact of a direct STAT3 inhibitor on the tumor microenvironment and PD-1 blockade efficacy in HCC models.Orthotopic mouse models of HCC (RIL-175 and HCA-1 grafts in syngeneic mice) were used to test the efficacy of the selective STAT3 inhibitor STX-0119 alone or combined with anti-PD-1 antibodies. We evaluated the effects of therapy on tumor vasculature and the immune microenvironment using immunofluorescence (IF), cell viability assay and quantitative real-time (qRT)-PCR in tumor tissues.Combining anti-PD-1 antibodies with a STX-0119 failed to show a growth delay or survival benefit compared to each agent alone or control in any of the HCC models. Interestingly, evaluation of intratumoral CD8+ T cell infiltration by IF showed a significant increase after one-week treatment with STX-0119 (p=0.034). However, STX-0119 treatment simultaneously promoted increased immunosuppression in the tumor microenvironment by increasing the proportion of Tregs, tissue hypoxia and α-SMA activated cancer-associated fibroblasts (CAFs) measured by IF. Consistent with these findings, we found increased immature tumor vessels by IF and VEGF, Tgf-β and Vash2 expression by qPCR.Pharmacologic STAT3 inhibition could significantly enhance CD8

Obesity is a major problem worldwide and has been associated with colorectal cancer development, among other diseases. Ephrin receptors and ligands play an important role in the turnover of the intestinal mucosa and intestinal crypt compartmentalization. It has been hypothesised that obesity-induced inflammation affects ephrin signals, leading to carcinogenesis. Therefore, the aim of the present study was to assess the relationship between Eph-ephrin B signalling, obesity and obesity-associated colorectal cancer. An azoxymethane-induced obesity-associated cancer KKAy mouse model developed in our prior study was used. A total of 46 patients with consecutive colorectal cancer and 48 tumours were analysed. Immunohistological analyses were performed in mouse and human samples, and immunoreactive scores (IRS) were determined. KKAy mice were significantly more prone to cancer development compared with control C57/BL mice (2/15 in C57/BL vs. 10/10 in KKAy; P0.001). TUNEL assay revealed a lower number of apoptotic cells in normal mucosa of KKAy mice (8.8% in C57/BL vs. 3.2% in KKAy; P0.001) and obese patients (9.2% with BMI25 vs. 3.6% with BMI ≥25; P=0.021). Immunohistological analysis revealed that ephrin-B1 was downregulated in normal mucosa from KKAy mice and obese patients (IRS, 2.86 with BMI25 vs. 6.00 with BMI ≥25; P=0.002). Moreover, EphB2 was downregulated in tumours from KKAy mice and obese patients (IRS, 6.58 with BMI25 vs. 3.83 with BMI ≥25; P0.001). The distribution of infiltrated macrophages corresponded to the MCP-1 expression pattern in KKAy mice, and the number of macrophages was also significantly higher in those mice (36.3 in C57/BL vs. 120.0 in KKAy; P=0.029). The findings suggested that obesity results in disruption of EphB2/ephrin-B1 signalling, promoting colorectal cancer development and progression.

Aim: To evaluate the significance of next-generation sequencing-based gene panel testing in surgically resectable colorectal cancer by analyzing real-world data. Materials & methods: A total of 107 colorectal cancer patients who underwent curative surgery were included, and correlations between next-generation sequencing data and clinicopathological findings were evaluated. Results: More combination patterns in gene alteration were identified in advanced-stage tumors than in early-stage tumors. The copy number alteration count was significantly lower in right-sided colon tumors and early-stage tumors. Homologous recombination deficiency was more often identified in advanced-stage tumors, and high homologous recombination deficiency status was useful for identifying high-risk stage II tumors. Conclusion: Homologous recombination deficiency was identified as a useful result of gene panel testing with novel utility in clinical practice.

Background/aim In previous work we showed that expression of heat-shock protein 27 (HSP27; encoded by HSPB1) was associated with inherent resistance to 5-fluorouracil (5-FU). However, the relationship between HSP27 and acquired resistance remains unknown. Materials and methods We generated an acquired resistance model (WiDr-R) of a colon cancer cell line by exposing WiDr cells to 5-FU. Cell viability assays under treatment with 5-FU, as well as down-regulation of HSP27 using small interfering HSP27 RNA, were performed. HSP27 mRNA and protein expression was analyzed using real-time polymerase chain reaction and western blotting. Results 5-FU-acquired resistance induced overexpression of HSP27 mRNA and protein levels in WiDr-R cells. Furthermore, siRNA knockdown of HSP27 in WiDr-R cells reduced 5-FU-acquired resistance. Conclusion These findings demonstrate that HSP27 is associated with 5-FU resistance in human colon cancer cell cells and suggest that HSP27 regulation represents a novel approach to overcoming chemoresistance in colorectal cancer.

The aim of this study was to clarify the role of Methicillin-resistant Staphylococcus aureus (MRSA) carriers in the development of surgical site infection (SSI) after colorectal surgery.MRSA is commonly implicated in hospital-acquired infections. Active surveillance culture (ASC) using the nasal swab test is useful to detect MRSA in surgical patients. We hypothesized that MRSA carriers would be more susceptible to SSI after colorectal surgery METHODS: Patients who underwent ASC between 2010 and 2013 were included in this study. The incidence of SSI was compared between MRSA carriers and non-carriers using the chi-square test. The odds ratio for SSI was computed using logistic regression analyses.Among 355 patients, 12 (3.4%) were identified as MRSA carriers and 343 as non-carriers. Of all the patients, 65 patients (18.3%) developed an SSI. Of these, 6 cases were in MRSA carriers and 59 cases were in non-carriers (p 0.01). This meant that half of the 12 MRSA carriers developed an SSI, compared with only 17.2% of non-carriers (59 cases out of 343 patients). Therefore, MRSA carriers had a significantly higher risk of SSI (adjusted odds ratio = 4.77 [1.37 to 16.6], p = 0.01).Detection of MRSA via ASC is significantly associated with the development of SSI after colorectal surgery. These findings indicate that ASC for MRSA is useful to predict an SSI.

Several recent studies suggest that serum anti-p53 antibodies (s-p53-Abs) may be combined with other markers to detect esophageal and colorectal cancer. In this study, we assessed the sensitivity and specificity of s-p53-Abs detection of a new electrochemiluminescence immunoassay (ECLIA; Elecsys anti-p53). Elecsys anti-p53 assay was used to analyze the level of s-p53-Abs in blood sera from patients with esophageal or colorectal cancer taken before treatment. Control blood sera from healthy volunteers, patients with benign diseases, and patients with autoimmune diseases served as a reference. In addition, squamous cell carcinoma antigen (SCC-Ag) and cytokeratin 19 fragments (CYFRA21-1) were assessed in patients with esophageal cancer, and carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 were assessed in patients with colorectal cancer. Samples from 281 patients with esophageal cancer, 232 patients with colorectal cancer, and 532 controls were included in the study. The median value of s-p53-Abs in control samples was

Introduction Recently, clinical studies have revealed that smoking can contribute to the poor prognosis of colorectal cancer (CRC) and, additionally, can be a risk factor for pulmonary metastasis of CRC. However, there has been no basic research regarding the underlying molecular mechanism. The purpose of this study was to clarify the mechanism by which smoking causes pulmonary metastasis of CRC. Methods First, pulmonary metastasis model mice inhaled cigarette smoke or air (control) for 1 h once a day for 3 weeks. We attempted to clarify the effect of smoking on the incidence of pulmonary metastasis. On the 15th day, CMT-93 cells were injected into the tail vein. At 6 and 8 weeks following injection, the extent of pulmonary metastasis was evaluated using in vivo micro CT. After the last CT examination, the mice were sacrificed, and the lungs were extracted for pathological examination. Results The number of mice with pulmonary metastases in the smoking group was significantly higher than in the control group. Three weeks of smoking induced mild inflammation in the lungs, as evidenced by increases in the levels of IL-6 and TNF-α in bronchoalveolar lavage. Moreover, the adhesion-related molecule ICAM-1 was overexpressed in pulmonary tissue, which allowed drained cancer cells to remain in the lung and contribute to the formation of pulmonary metastasis. Conclusion Collectively, cigarette smoking may contribute to the pathogenesis and development of pulmonary metastasis in CRC through enhancement of adhesion and inflammation.

Mung bean (Vigna radiata) is an immunomodulatory medicinal plant, which is recognized as a component of a traditional postpartum diet. The liver plays a crucial role in fatty acid synthesis under t...

Recent clinical and experimental evidence has evoked the concept of the gut–brain axis to explain mutual interactions between the central nervous system and gut microbiota that are closely associated with the bidirectional effects of inflammatory bowel disease and central nervous system disorders1–4. Despite recent advances in our understanding of neuroimmune interactions, it remains unclear how the gut and brain communicate to maintain gut immune homeostasis, including in the induction and maintenance of peripheral regulatory T cells (pTreg cells), and what environmental cues prompt the host to protect itself from development of inflammatory bowel diseases. Here we report a liver–brain–gut neural arc that ensures the proper differentiation and maintenance of pTreg cells in the gut. The hepatic vagal sensory afferent nerves are responsible for indirectly sensing the gut microenvironment and relaying the sensory inputs to the nucleus tractus solitarius of the brainstem, and ultimately to the vagal parasympathetic nerves and enteric neurons. Surgical and chemical perturbation of the vagal sensory afferents at the hepatic afferent level reduced the abundance of colonic pTreg cells; this was attributed to decreased aldehyde dehydrogenase (ALDH) expression and retinoic acid synthesis by intestinal antigen-presenting cells. Activation of muscarinic acetylcholine receptors directly induced ALDH gene expression in both human and mouse colonic antigen-presenting cells, whereas genetic ablation of these receptors abolished the stimulation of antigen-presenting cells in vitro. Disruption of left vagal sensory afferents from the liver to the brainstem in mouse models of colitis reduced the colonic pTreg cell pool, resulting in increased susceptibility to colitis. These results demonstrate that the novel vago-vagal liver–brain–gut reflex arc controls the number of pTreg cells and maintains gut homeostasis. Intervention in this autonomic feedback feedforward system could help in the development of therapeutic strategies to treat or prevent immunological disorders of the gut. A liver–brain–gut neural circuit responds to the gut microenvironment and regulates the activity of peripheral regulatory T cells in the colon by controlling intestinal antigen-presenting cells in a muscarinic signalling-dependent manner.

Patients with longstanding inflammatory bowel disease are at high risk of developing intestinal cancers. In this study, we aimed to elucidate the differences between intestinal cancers associated with ulcerative colitis and Crohn's disease.Intestinal cancers in ulcerative colitis and Crohn's disease patients treated between 1983 and 2020 at 43 Japanese institutions were retrospectively analyzed..A total of 1505 intestinal cancers in 1189 ulcerative colitis and 316 Crohn's disease patients were studied. Almost all of ulcerative colitis-associated cancers (99%) were in the colon and rectum, whereas half of Crohn's disease-associated cancers (44%) were in the anus, with 11% in the small intestine. Ulcerative colitis-associated cancers were diagnosed more frequently by surveillance (67% vs. 25%, P 0.0001) and at earlier stages (stages 0-1, 71% vs. 27%, P 0.0001) compared with Crohn's disease-associated cancers. Colorectal cancers associated with Crohn's disease showed a significantly worse 5-year overall survival rate than those associated with ulcerative colitis (stage 2, 76% vs. 89%, P = 0.01, stage 3, 18% vs. 68%, P = 0.0009, and stage 4, 0% vs. 13%, P = 0.04). Surveillance correlated with earlier diagnoses for ulcerative colitis- and Crohn's disease-associated intestinal cancers, whereas shorter intervals between endoscopic examinations correlated with an earlier cancer diagnosis in ulcerative colitis patients but not in Crohn's disease patients.The clinical and oncological features of ulcerative colitis- and Crohn's disease-associated cancers were very different. Crohn's disease-associated cancers were diagnosed at more advanced stages and were detected less frequently by surveillance. Additionally, they showed a significantly poorer prognosis.

Purpose: This study aimed to evaluate the significance of Next-generation sequencing (NGS)-based gene panel testing in resectable colorectal cancers (CRC)s by analyzing real-world data collected prospectively from patients. Methods: Patients with CRC who underwent surgery from July 2018 to February 2020 at our institution were included, and correlations between various NGS data and clinicopathological findings were evaluated. Results: Overall, 107 patients were included in this study. The tumor stage was I in 28 cases (26.2%), II in 40 cases (37.4%), III in 32 cases (29.9%), and IV in 7 cases (6.5%). Actionable gene alterations were found in 97.2% of the cases. Co-alteration analysis suggested that either TP53- or APC-related alterations were more frequently found in early-stage tumors (stage I). The copy number alteration count was significantly lower in right side colon tumors than in tumors in other locations (P < 0.05). Homologous recombination deficiency (HRD) was more often identified in stage IV tumors than in stage I or II tumors (P < 0.05). Moreover, high HRD status was suggested to be useful for identifying high-risk stage II tumors (P < 0.05). Conclusion: In this study, real-world NGS data represented the biological features of CRCs. HRD was identified as a useful result of gene panel testing with novel utility in clinical practice.

ObjectiveThis study aims to indicate whether the CT value of the mesorectum could be correlated with the incidence of anastomotic leakage (AL) in laparoscopic surgery for rectal cancer.MethodsThe study subjects included 173 patients who underwent laparoscopic anterior resection (LAR) for rectal cancer from September 2005 to 2016 in our institution as well as reliable contrast-enhanced CT preoperatively. Univariate and multivariate analyses were performed to determine the correlation between surgical outcomes, including AL and CT value of the mesorectum.ResultsAL was observed in 30 (17.3%) patients. Amongst short-term surgical outcomes, overall complication showed significant correlation with the CT value of the mesorectum (P = 0.003). In addition, AL was the only factor, which significantly correlated with the CT value of the mesorectum (P = 0.017). By plotting receiver operating characteristic curve, −75 HU was the threshold of the CT value of the mesorectum for predicting AL with an area under the curve of 0.772. Categorized into two groups as per the threshold, low group showed significantly higher incidence of AL (OR, 2.738; 95% CI, 1.105–6.788; P = 0.030) as well as whole complications (OR, 4.431; 95%CI, 1.912–10.266; P = 0.001).ConclusionThe CT value of the mesorectum may be a helpful preoperative radiological biomarker to predict AL after LAR for rectal cancer.

BackgroundMetformin is a commonly used drug for the treatment of diabetes. Accumulating evidence suggests that it exerts anti-cancer effects in many cancers, including colorectal cancer. However, the underlying molecular mechanisms of colorectal cancer metastasis remain unclear.MethodsColorectal cancer cell lines were treated with metformin, and cell proliferation, invasion, and migration were analyzed in vitro. The relationship between metformin and the AMPK–mTOR axis was assessed by western blot analysis and transfection with small interfering RNA. A colorectal cancer xenograft mouse model was used to observe the effects of metformin on liver metastasis. Immunohistochemical analysis was performed on liver metastatic tumors.ResultsIn in vitro experiments, metformin significantly inhibited the proliferation, migration, and invasion only in HCT116 and SW837 cells, but not in HCT8 and Lovo cells. Only in HCT116 and SW837, a change in AMPK–mTOR expression was observed in a dose-dependent manner. In colorectal cancer xenograft mice, the liver metastatic rate (10% vs. 50%, p = 0.05) and the number of liver metastatic nodules (0.1/body vs. 1.2/body, p = 0.04) were significantly lower in the metformin group. Tumor proliferation and EMT were decreased and apoptosis was promoted only in metastatic liver tumors of mice treated with metformin.ConclusionThe molecular mechanism of the anti-cancer effects of metformin involves repression of mTOR pathways via AMPK activation. Moreover, the differences in metformin sensitivity depend on the response of the AMPK–mTOR pathway to metformin. Our study provides a theoretical basis for the anti-metastatic treatment of colorectal cancer using metformin.

Purpose Angiopoietin-like 4 (ANGPTL4) was recently shown to be associated with cancer progression but little is known about its contribution to cancer metabolism. The purpose of this study was to elucidate the role of ANGPTL4 in glucose metabolism in colorectal cancer (CRC). Methods Immunohistochemical staining of CRC specimens classified 84 patients into two groups according to ANGPTL4 expression. Clinicopathological characteristics, gene mutation status obtained by next-generation sequencing, and fluorodeoxyglucose (FDG) uptake measured by positron emission tomography/computed tomography (PET/CT) were compared between the two groups. Furthermore, the impact of ANGPTL4 expression on cancer metabolism was investigated by a subcutaneous xenograft mouse model using the ANGPTL4 knockout CRC cell line and glucose transporter (GLUT) expression was evaluated. Results There were significantly more cases of T3/4 tumours (94.3% vs. 57.1%, P < 0.001) and perineural invasion (42.9% vs. 22.4%, P = 0.046) in the ANGPTL4-high group than in the low group. Genetic exploration revealed a higher frequency of KRAS mutation (54.3% vs. 22.4%, P = 0.003) in the ANGPTL4-high tumours. All the FDG uptake parameters were significantly higher in ANGPTL4-high tumours. In vivo analysis showed a significant reduction in tumor size due to ANGPTL4 knockout with lower expression of GLUT1 and GLUT3, and suppression of AKT phosphorylation. Conclusion ANGPTL4 regulates the expression of GLUTs by activating the PI3K-AKT pathway and thereby promoting glucose metabolism in CRC. These findings establish a new functional role of ANGPTL4 in cancer progression and lay the foundation for developing a novel therapeutic target.

Imaging and measuring compression stresses secure a safe and healthy life. Compression stresses in kPa range are not easily detected by conventional mechanoresponsive materials because microscopic molecular motion of the chromophores is not induced by such weak stresses. Moreover, imaging of the stress distribution is not achieved so far. The present study shows a sponge device combining two stimuli-responsive materials, a capsule releasing interior liquid and color-changing polymer in responses to compression stress and chemical stimulus, respectively. The stimuli-responsive capsule is dispersed on a melamine sponge comprised of the fibers with coating the layered polydiacetylene (PDA). The application of weak compression stresses induces collapse of the capsules, outflow of the interior liquid, and subsequent irreversible color change of PDA. The cascading response in the sponge device colorimetrically enables imaging of the distribution and measuring the strength of the compression stresses in kPa range. Furthermore, the device demonstrates imaging and measuring unknown weak compression stresses applied by the irregular-shaped objects. A couple of clinical issues in surgical operation of intestine are studied using the stress-imaging sponge device. The device and its design strategy can be applied to stress imaging in a variety of fields.

Organ/space surgical site infection (SSI) is a significant clinical problem. The postdiagnosis course of organ/space SSIs and the impact of its early diagnosis on clinical outcomes are yet to be clarified. Thus, we aimed to investigate the association between the timing of diagnosis and the clinical outcome of organ/space SSI.This retrospective, single-center cohort study evaluated patients who underwent elective gastrointestinal or hepatopancreatobiliary surgery between 2016 and 2020. Clinical outcomes were compared between the early group (ie, SSI diagnosed until postoperative day [POD] 4) and normal-late group (ie, SSI diagnosed after POD 5). The primary outcome was the final C-reactive protein (CRP) level within 14 d after organ/space SSI diagnosis.In total, 110 patients were evaluated. The median time of diagnosis was 7 d postoperatively (interquartile range, 5-9 d postoperatively). Compared with the normal-late group, the early group included a higher proportion of patients with Clavien-Dindo grade ≥IIIb (8/21 vs 11/89,Early diagnosed organ/space SSI are originally severe and may therefore be detected earlier. Importantly, early diagnosed organ/space SSI is likely to be severe and refractory.