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Managing colon cancer with intestinal nonrotation, a type of congenital intestinal malrotation, is challenging due to the presence of anatomical abnormalities and severe adhesions. When patients have nonrotation, it is markedly more difficult to determine which vessels correspond to the colic vessels and ileal vessels until all vascular branching patterns become evident. The optimal approach for right‐sided colon cancer with intestinal nonrotation has yet to be established. In the present case of ascending colon cancer with intestinal nonrotation, we performed laparoscopic right hemicolectomy with D3 dissection using a modified cranial approach. This approach involves tracing, without resecting, branches from the superior mesenteric vein and superior mesenteric artery in a cranial‐to‐caudal manner until the ileocolic artery and ileocolic vein, which course toward the cecum, are identified, followed by the dissection of the colic vessels and lymph nodes in a caudal‐to‐cranial fashion. [ABSTRACT FROM AUTHOR]

Aim Method Results Conclusion The purpose of this Dutch retrospective population‐based study was to evaluate how short‐term outcomes and inter‐hospital variability after right hemicolectomy for colon cancer have evolved between 2012 and 2020.Patients who underwent right hemicolectomy for primary solitary colon cancer between 1 January 2012 and 31 December 2020 and were registered in the Dutch Colorectal Audit were included. Surgical characteristics and outcomes were assessed during three time periods (2012–2014, 2015–2017, 2018–2020). Complications and mortality were the primary outcomes, and reintervention, readmission and length of stay secondary outcomes.In total, 29 274 patients were included. Significant increase in minimally invasive surgery (51.1% 2012–2014, 73.2% 2015–2017, 85.0% 2018–2020), increase in conversion (6.6%, 7.8%, 9.1%, P < 0.001) and decrease in acute/urgent resections (15.9%, 11.7%, 10.9%, P < 0.001) were found. The overall complication rate was slightly lower in the third period (30.9%, 30.6%, 28.8%, P = 0.004), primarily because of decreasing non‐surgical complications (19.7%, 20.6%, 17.6%, P < 0.001), while surgical complications remained unchanged (17.5%, 18.3%, 18.2%, P = 0.277). Postoperative mortality was 3.4%, 2.3% and 3.5%, respectively. Reintervention rate slightly decreased (9.4%, 8.3%, 8.6%, P < 0.001). The proportion of patients admitted for more than 6 days decreased over time (54.3%, 42.4%, 34.3%, P < 0.001), with an increase in readmission rate (7.4%, 6.8%, 9.3%, P < 0.001). Inter‐hospital variability decreased over time for complications, length of stay and conversion.This study shows a national decreasing inter‐hospital variability in clinical outcomes after right hemicolectomy and a decrease in postoperative complications. Despite increasing use of laparoscopy, surgical complications and mortality remained stable over time. [ABSTRACT FROM AUTHOR]

Xylooligosaccharides (XOS) are considered a potent source of prebiotics for humans. The global prebiotic market is expanding in size, was valued at USD 6.05 billion in 2021, and is expected to grow at a 14.9% compound annual growth rate between 2022 and 2030, indicating a huge demand. These XOS are non‐digestible pentose sugar oligomers comprising mainly xylose. Xylose is naturally present in the lignocellulosic biomass (LCB), fruits and vegetables. Apart from the prebiotic effect, these XOS have been reported to reduce blood cholesterol, possess antioxidant effects, increase calcium absorption, reduce colon cancer risk, and benefit diabetic patients. The primary use of XOS is reported in the feed industry followed by health, medical use, food and drinks. LCB mainly contains glucan, xylan and lignin. After glucan, xylan is the second‐highest available sugar on the globe composed of xylose. Therefore, the xylan fraction of LCB has great significance in producing food, feed and energy. Glucan has been exploited for the commercial production of ethanol, xylitol, furfural, hydroxymethyl furfural and glucose. As of now, xylan has limited applications. Therefore, xylan can be exploited to convert to XOS. The production of XOS from LCB fraction not only helps to produce these at a very low price, but also helps in the reduction of greenhouse gases. Its use in food and drinks is increasing as it can be derived from the abundantly and cheaply available LCB. The article provides a review on the production, purification and characterization of XOS in view of their use as nutraceuticals. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Objective: Splenic flexure mobilization (SFM) is a major challenge in laparoscopic left hemicolectomy. This study aims to assess the safety and effectiveness of the pancreas-guided SFM technique during laparoscopic left hemicolectomy. Methods: From January 2018 to December 2023, 352 patients with left-sided colon cancer underwent laparoscopic left hemicolectomy. Based on the SFM method used, the patients were divided into the pancreas-guided group (167 cases) or the "Three Approaches Roundabout"/classic group (185 cases). Clinicopathologic characteristics and intraoperative and postoperative variables were compared between the two groups. Results: The two groups had no significant differences in baseline indicators (P > 0.05). All surgeries were successful without needing to convert to laparotomy, and there were no combined organ resections involving the spleen or pancreas in either group. The mean duration of surgery was significantly lower in the pancreas-guided group than in the classic group (P < 0.01). The median volume of intraoperative blood loss in the pancreas-guided group was lower than that in the classic group (P < 0.01). Through video playback, it was found that the retro-pancreatic space had been entered during operation in 8 cases (4.3%) in the classic group, while there were no such occurrences in the pancreas-guided group. This difference was statistically significant (P < 0.05). The difference in the number of lymph nodes cleared, postoperative hospital stays, and incidence of complications were not statistically significant (all P > 0.05) between the groups. Conclusion: The pancreas-guided SFM technique is a safe and feasible option for laparoscopic left hemicolectomy. Our study's findings suggest that this approach facilitates accurate access to the correct anatomic plane, potentially improving surgical efficiency. [ABSTRACT FROM AUTHOR]

Ovarian cancer (OC) is the deadliest gynecological malignancy, having a high mortality rate due to its asymptomatic nature, chemoresistance, and recurrence. However, the proper mechanistic knowledge behind these phenomena is still inadequate. Cancer recurrence is commonly observed due to cancer stem cells which also show chemoresistance. We aimed to decipher the molecular mechanism behind chemoresistance and stemness in OC. Earlier studies suggested that PITX2, a homeobox transcription factor and, its different isoforms are associated with OC progression upon regulating different signaling pathways. Moreover, they regulate the expression of drug efflux transporters in kidney and colon cancer, rendering chemoresistance properties in the tumor cell. Considering these backgrounds, we decided to look for the role of PITX2 isoforms in promoting stemness and chemoresistance in OC cells. In this study, PITX2A/B has been shown to promote stemness and to enhance the transcription of ABCB1. PITX2 has been discovered to augment ABCB1 gene expression by directly binding to its promoter. To further investigate the regulatory mechanism of PITX2 gene expression, we found that TGFβ signaling could augment the PITX2A/B expression through both SMAD and non-SMAD signaling pathways. Collectively, we conclude that TGFβ1-activated PITX2A/B induces stem-like features and chemoresistance properties in the OC cells. Graphical illustration depicts that TGFβ1 enhances PITX2A/B expression through ERK and SMAD signaling pathway. Then, PITX2A/B bind ABCB1 promoter and therefore induce stemness and chemoresistance properties in OC cells. [ABSTRACT FROM AUTHOR]

Activating transcription factor 4 (ATF4) plays a central role in the integrated stress response (ISR) and one overlapping branch of the unfolded protein response (UPR). We recently reported that the splicing inhibitor isoginkgetin (IGG) induced ATF4 protein along with several known ATF4-regulated transcripts in a response that resembled the ISR and UPR. However, the contribution of ATF4-dependent and -independent transcriptional responses to IGG exposure was not known. Here we used RNA-sequencing in HCT116 colon cancer cells and an isogenic subline lacking ATF4 to investigate the contribution of ATF4 to IGG-induced changes in gene expression. Approximately 85% of the IGG-responsive DEGs in HCT116 cells were also differentially expressed in response to the ER stressor thapsigargin (Tg) and these were enriched for genes associated with the UPR and ISR. Most of these were positively regulated by IGG with impaired responses in the ATF4-deficient cells. Nonetheless, there were DEGs that responded similarly in both cell lines. The ATF4-independent IGG-induced DEGs included several metal responsive transcripts encoding metallothionines and a zinc transporter. Taken together, the predominant IGG response was ATF4-dependent in these cells and resembled the UPR and ISR while a second less prominent response involved the ATF4-independent regulation of metal responsive mRNAs. [ABSTRACT FROM AUTHOR]

Cisplatin and oxaliplatin cause the secretion of high mobility group box 1 (HMGB1) protein from cancer cells, which is necessary for initiation of immunogenic cell death (ICD). Calreticulin (CRT) translocation from the endoplasmic reticulum to the plasma membrane is also required; oxaliplatin induces this translocation but cisplatin does not. We have discovered that oxaliplatin causes the secretion of both HMGB1 and HMGB2 from the cell nucleus into the extracellular milieu. We previously showed that cisplatin-mediated secretion of HMGB1 is controlled by the nuclear exporter XPO1 (chromosomal maintenance 1; CRM1). We now find that XPO1 regulates oxaliplatin-mediated secretion of both HMGB1 and HMGB2. XPO1 inhibition causes nuclear accumulation of both proteins, inhibition of oxaliplatin-mediated ferroptosis of colon cancer cells, and inhibition of CRT translocation to the plasma membrane of lung and colon cancer cells. Incubation of cancer cells with cell targeted (CT)-HMGB2 confirmed that HMGB2 is required for the CRT translocation. Furthermore, CT-HMGB2 is three orders of magnitude more potent at inducing CRT translocation than oxaliplatin. The paradox that immunologic cancer cell death is caused by oxaliplatin but not cisplatin has been resolved. Only oxaliplatin secretes HMGB2 to induce translocation of calreticulin to the plasma membrane, which is required for immunologic cell death. [ABSTRACT FROM AUTHOR]

In this paper we study existence and uniqueness of solution stochastic differential equations involving fractional integrals driven by Riemann-Liouville multifractional Brownian motion and a standard Brownian. Then, we obtain approximate numerical solution of our problem and colon cancer chemotherapy effect model are presented to confirm our results. We show that considering time dependent Hurst parameters play an important role to get more realistic results. [ABSTRACT FROM AUTHOR]

Ciliated muconodular papillary tumor (CMPT) is a rare pulmonary tumor, typically occurring in middle-aged and elderly individuals. The molecular mutation spectrum of CMPT remains insufficiently explored. Commonly known driver gene alterations include KRAS, BRAF, EGFR, and ALK rearrangement. This report details the clinicopathological features of 2 patients presenting with CMPT as pulmonary nodules during clinical examinations. Microscopic analysis revealed tumors with glandular or papillary structures, consisting of mucinous cells, ciliated columnar cells, and basal cells. Notably, both patients exhibited STRN::ALK fusion, a finding not previously associated with CMPT. STRN::ALK fusion serves as a target for therapy in various tumors, including non-small cell lung cancer, thyroid cancer, and colon cancer. Consequently, we conducted a review of relevant literature, summarizing the clinicopathological and molecular characteristics of CMPT to facilitate further research. Our insights enhance the understanding of this uncommon tumor and contribute to the expansion of its molecular alteration spectrum. [ABSTRACT FROM AUTHOR]

Colorectal carcinoma (CRC) is one of the most common malignant tumors in the digestive tract. It was found that butyric acid could inhibit the expression of miR-183 to slow down malignant progression of CRC in the early stage. However, its regulatory mechanism remains unclear. This study screened the IC50 value of butyrate on inhibition of CRC cells malignant progression. Its inhibitory effects were detected by MTT assay, colony formation experiment, Transwell migration experiment, and apoptosis evaluation by flow cytometry. Next, the expressions of miR-183 and DNAJB4 were, respectively, determined in butyrate treated and miR-183 analog or si-DNAJB4-transfected CRC cells to further detect the role of upregulated miR-183 or silencing DNAJB4 in CRC cells malignant progression. Subsequently, the targeted regulatory relationship between miR-183 and si-DNAJB4 was confirmed by bioinformatic prediction tools and double luciferase report genes analysis method. The regulatory mechanism of butyrate on miR-183/DNAJB4 axis signal pathway was evaluated in molecular level, and verified in nude mouse xerograft tumor model and immunohistochemical analysis tests of Ki67 positive rates. The results displayed that butyrate with increased concentration can hinder the proliferation and improve apoptosis of CRC cells by decreasing the expression of miR-183. Thus, butyrate reduces miR-183 expression and increases DNAJB4 expression via the miR-183/DNAJB4 axis, ultimately inhibiting the malignant progression and increasing apoptosis of CRC. While over expression of miR-183 downregulate the expression of DNAJB4, which can reverse the inhibitory effect of butyrate. [ABSTRACT FROM AUTHOR]

Background: Ginseng polysaccharide (GPS) is an ingredient of ginseng with documented anti-tumor properties. However, its effect on colon cancer and the underlying molecular mechanisms have not been investigated clearly. Methods: Cell viability of HT29 and CT26 cells treated with different concentrations of GPS was assessed using the Cell Counting Kit-8 (CCK-8) assay. Western blot assay was used to detect the expression of apoptotic proteins, while the mRNA levels were assessed by real-time quantitative polymerase chain reaction (RT-qPCR). Transwell migration assays were used to examine the migration and invasion of cells. Results: The results revealed that GPS effectively suppressed the proliferation of HT29 and CT26 cells. We demonstrated an upregulation of apoptotic proteins in GPS-treated cells, including Bax, cleaved Caspase-3, and p-p53. GPS treatment also increased the mRNA levels of cytochrome C and Bax. Furthermore, the results showed that GPS treatment concurrently promoted the activation of nucleotide-binding domain leucine-rich family pyrin-containing 3 (NLRP3) inflammasome. Transwell migration assays showed that GPS inhibited the migratory and invasive abilities of colon cancer cells. As expected, inhibition of NLRP3 expression using INF39 attenuated the inhibitory effect of GPS on migration and invasion. Upon NLRP3 inhibition, GPS-induced apoptosis was dramatically alleviated, accompanied by a reduction in the expression of apoptotic proteins. Conclusion: In conclusion, this research provides compelling evidence that the GPS-induced NLRP3 signaling pathway plays a pivotal role in apoptosis of colon cells, suggesting potential clinical implications for the therapeutic intervention of colon cancer. Thus, GPS might be a promising anti-tumor drug for the treatment of colorectal cancer. [ABSTRACT FROM AUTHOR]

Purpose: Few studies have investigated the impact of the surgical proximal and distal margins on colon cancer recurrence. We conducted this study to investigate the effect of resection margins on the prognosis of resectable colon cancer. Methods: We analyzed data on 1458 patients who underwent colorectal resection in our institute between January, 2004 and March, 2020, including 579 patients with resectable colon cancer. The association between the resection margin and recurrence for each oncological status was assessed and the value of the resection length that influenced recurrence was analyzed. Results: Patients who had pT4 colon cancer with margins of more than 7 cm had a trend of fewer recurrences and longer relapse-free survival (RFS) than those with colon cancer of other stages (P = 0.033; hazard ratio [HR], 0.42; 95% confidence interval [CI], 0.20–0.89). Multivariate analysis identified a margin of < 7 cm as an independent risk factor for RFS in patients with pT4 colon cancer (P = 0.023; HR, 2.65; 95% CI 1.013–6.17). No correlation was found between resection margins and recurrence, depending on the extent of lymph node metastasis and tumor location. Conclusion: A resection margin of at least 7 cm should be maintained for patients with pT4 colon cancer. [ABSTRACT FROM AUTHOR]

Purpose: This study investigated the impact of sidedness of colorectal cancer (CRC) in elderly patients on the prognosis. Methods: In a sub-analysis of a multicenter case–control study of CRC patients who underwent surgery at ≥ 80 years old conducted in Japan between 2003 and 2007, both short- and long-term outcomes were compared between right-sided colon cancers (RCCs) and left-sided colorectal cancers (LCCs). RCCs were defined as those located from the cecum to the transverse colon. Results: Among the 1680 patients who underwent curative surgery, 812 and 868 had RCCs and LCCs, respectively. RCCs were more frequent than LCCs in those who were female, had renal comorbidities, and had a history of abdominal surgery. Regarding tumor characteristics, RCCs were larger, invaded more deeply, and were diagnosed as either mucinous or signet ring-cell carcinoma more frequently than LCCs. Regarding the prognosis, patients with RCCs had a significantly longer cancer-specific survival (CS-S) and cancer-specific relapse-free survival (CS-RFS) than those with LCCs. Furthermore, sidedness was determined to be an independent prognostic factor for CS-S and CS-RFS. Conclusion: RCCs, which accounted for half of the cases in patients ≥ 80 years old, showed better long-term outcomes than LCCs. [ABSTRACT FROM AUTHOR]

Introduction: The anastomotic leak (AL) is one of the most feared complications of colorectal surgery, since it is associated with a high rate of morbidity, mortality, length of hospital stay and cost of care. Our aim was to determine the risk factors associated with anastomosis leak in colorectal cancer patients who underwent surgical resection with anastomosis. Methods: A multicentre observational, analytical, retrospective and case-control study was carried out. For each case, two controls were included from three national hospitals from Lima, Peru during the period 2021-2022. To determine the degree of association, multivariate logistic regression model was carried out. Results: A total of 360 patients were included, 120 from each hospital. The mean age of the population was 68.03 ± 14.21 years old. The majority were 65 years old or older (66.1%), 52.8% were female, and 63.3% had clinical stage III. The 40% of the patients had albumin levels lower than 3.5 g/dL. Regarding the surgery, 96.4% were elective, 68.9% underwent open approach, and 80.8% had an operative time of more than 180 minutes. Most of them had right colon cancer (50.8%). In the multivariate analysis, a significant association was found with the age variable (OR = 2.48; 95%CI:1.24-4.97), clinical tumour level (OR = 2.71; 95%CI:1.34-5.48), American Society of Anesthesiologists (ASA) Score (OR = 3.23; 95%CI:1.10-9.50), preoperative serum albumin (OR = 22.2; 95%CI:11.5-42.9). Conclusion: The most important independent risk factors associated with AL among patients with colorectal cancer were pre-operative such as lower preoperative serum albumin levels, followed by a higher ASA Score, clinical-stage III-IV, and an age ≥65 years old. [ABSTRACT FROM AUTHOR]

Objectives: The incidence of colorectal cancer (CRC) has exhibited regional variability in North Africa and the Middle East, with a steady increase in Algeria. Despite this trend, limited data exist on the epidemiology of CRC in northwestern Algeria. Our study aimed to investigate the epidemiological characteristics of CRC in this region. Methods: We conducted a retrospective study examining 255 confirmed CRC cases through medical records from patients at the Sidi Bel Abbes anti-cancer centre. Results: The mean age of the study participants was 59 ± 13 years. The results showed a higher incidence in males (57%) than in females, and colon (62%) than rectal cancer. Within this cohort, 47% had a pre-existing medical condition, while 39% had a family history of cancer. Adenocarcinomas were the prevailing histological subtype in 94% of CRC cases. Compared with colon cancer, rectal cancer was less often diagnosed at stage IV of the disease (OR = 0.75; 95% CI = 0.09, 4.86; p = 0.8) and more likely in early-onset patients (OR = 2.27; 95% CI = 1.25, 4.17; p = 0.007). Men were at a higher risk of being diagnosed with metastatic CRC primarily hepatic metastases (OR = 2.03; 95% CI = 1.07, 3.99; p = 0.033) and pulmonary metastases (OR = 2.50; 95% CI = 1.07, 6.59; p = 0.045). Conclusion: This study may provide a comprehensive glimpse into CRC epidemiology in northwest Algeria. Understanding regional differences is the key to implementing specific preventive and interventional strategies. [ABSTRACT FROM AUTHOR]

Phyllostachys heterocycla is well-known for its high diversity of bioactive metabolites, which are the reason for its various potential medical uses for which anticancer activity has been proven. Herein, Phyllostachys heterocycla extract was prepared in two different metallic nanoparticle formulas such as iron oxide nanoparticle-boron, and iron oxide nanoparticle-humic acid (Fe2O3 NP-B and Fe2O3 NP-HA) with average particle sizes of 12.25 nm and 15.80 nm, respectively. Phyllostachys heterocycla extract and the two nano-formulas were investigated to obtain their cytotoxic activity. The crude extract exhibited potent cytotoxic activity against the ovarian (OVCAR-3) cancer cell line, with IC50 values of 16.3 µg/mL. In comparison, the two nano-loaded forms displayed a much more promising cytotoxic activity with IC50 values of 0.9 µg/mL for Fe2O3 NP-HA, and 6.4 µg/mL for Fe2O3 NP-B. Additionally, NP-HA and NP-B showed potent cytotoxic activities against prostate (PC-3) and pancreatic (Panc1) cancer cell lines with IC50 values of 2.31, 6.3 µg/mL for Fe2O3 NP-HA, and 14.9, 16.8 µg/mL for Fe2O3 NP-B. For apoptosis investigation, Fe2O3 NP-HA induced total ovarian apoptotic cell death by a 87.34-fold change, and necrosis by 1.29-fold change. Regarding cell cycle analysis, Fe2O3 NP-HA-PHE arrested the cell proliferation of OVCAR-3 cells in S-phase, with an increased cell population at S-phase of 42.6%. Additionally, it confirmed the apoptosis mechanism by inhibiting the antiapoptotic gene and activating the proapoptotic gene markers. Moreover, upon continuation of our phytochemical investigation of the plant, additional chemical components of the crude extract of Phyllostachys heterocycla were isolated using various chromatographic techniques. As a result, six compounds were isolated. By using different spectroscopic data, the chemical structures of the pure isolated compounds were assigned as stigmasterol (1), glyceryl monobehenate (2), vanillic acid (3), ferulic acid (4), catechin (5), and thymidine (6). These isolated compounds were previously reported for their potent cytotoxic activities against panel of cancer cell lines including pancreatic cancer and prostate cancer cell lines (Ferulic acid), beside the anti-tumor potential against ovarian cell lines (Stigmasterol). In addition to the cytotoxic activity against human larynx carcinoma HepG-2 cell lines (Catechin), human breast cancer MCF7 (Thymidine), and human colon cancer cell line HT-29 (Vanillic acid). Which may explain the significant cytotoxic and anticancer properities of the crude extract of Phyllostachysheterocycla. [ABSTRACT FROM AUTHOR]

Beilschmiedia acuta is a species of plant of the Lauraceae family and of the genus Beilschmiedia. The plant is used traditionally in the treatment of cancer and gastrointestinal infections. The plant has antibacterial and cytotoxic activities. In the present review, its cytotoxic potential was highlighted. It was found that the leaf and bark methanol extracts of the plant had cytotoxic toxic effects against several human cancer cell lines, including CCRF-CEM leukemia cells and its multidrug-resistant subline, CEM/ADR5000 cells, HCT116 p53+/+ colon cancer cells and its resistant clones HCT116 p53-/-, U87MG glioblastoma cells and its resistant U87MG.ΔEGFR subline, MDA-MB-231-pcDNA3 breast cancer cells, and its resistant subline, MDA-MB-231-BCRP as well as HepG2 hepatocarcinoma cells. It was also highlighted the leaf extract could be used to fight drug resistance of colon cancer. Further scientific investigations should be carried out on this plant to identify its bioactive constituents and to produce phytomedicines to combat several types of cancer. [ABSTRACT FROM AUTHOR]

Polyscias fulva (Hiern) Harms. (Araliaceae) is a medicinal plant used in the treatment of various types of illness including infectious diseases and cancers. The present chapter aimed at compiling the ethnopharmacological uses, the phytochemistry, and the cytotoxicity of this plant. P. fulva has many pharmacological properties including antioxidant, anti-inflammatory, antivenereal, antibacterial, antifungal, and anticancer activities. Botanicals from this plant had cytotoxic effects on several human cancer cell lines, including multidrug-resistant phenotypes such as P-glycoprotein overexpressing CEM/ADR5000 leukemia cells, breast cancer resistance protein-transfected (BCRP) MDA-MB-231-BCRP breast cancer cells, Tumor suppressor p53 knockout cells (HCT116 p53-/-) colon cancer cells, and mutation-activated epidermal growth factor receptor-transfected U87MG. ΔEGFR glioblastoma cells. P. fulva selectively showed antiproliferative effects against breast, prostate, colon, lung, stomach, and ovarian cancer, and hematological cancer cell lines. The cytotoxic phytochemicals identified in this plant include oleanolic acid, alpha-hederin, quercetin, β-sitosterol, and β-sitosterol-β-D-glucoside. Finally, P. fulva as well as its constituents may be useful in the development of novel drugs to fight cancer including the refractory phenotypes. [ABSTRACT FROM AUTHOR]

Objective: This large database study assessed whether extended pharmacologic prophylaxis for venous thromboembolism after colon cancer resection was associated with improved oncologic survival. Background: Heparin derivatives may confer an antineoplastic effect via a variety of mechanisms (eg, inhibiting angiogenesis in the tumor microenvironment). Studies evaluating the oncologic benefit of heparin and its derivatives have been limited in postsurgical patients. Multiple society guidelines recommend consideration of 30-day treatment with low molecular weight heparin to reduce venous thromboembolism risk after abdominopelvic cancer surgery. However, utilization of extended prophylaxis remains low. Methods: Surveillance, Epidemiology, and End Results-Medicare data were used to identify patients (age 65+) undergoing resection for nonmetastatic colon cancer from 2016 to 2017. The primary outcomes were overall and cancer-specific survival. Log-rank testing and multivariable Cox regression compared survival in patients who received extended prophylaxis versus those who did not in an inverse propensity treatment weighted cohort. Results: A total of 20,102 patients were included in propensity-weighting and analyzed. Eight hundred (3.98%) received extended pharmacologic prophylaxis. Overall survival and cancer-specific survival were significantly higher in patients receiving prophylaxis on log-rank tests (P=0.0017 overall, P= 0.0200 cancer-specific). Multivariable Cox regression showed improved overall survival [adjusted hazard ratio 0.66 (0.56-0.78)] and cancer-specific survival [adjusted hazard ratio 0.56 (0.39-0.81)] with prophylaxis after controlling for patient, treatment, and hospital factors. Conclusions: Extended pharmacologic prophylaxis after colon cancer resection was independently associated with improved overall and cancer-specific survival. These results suggest a potential antineoplastic effect from heparin derivatives when used in the context of preventing postsurgical venous thromboembolism. [ABSTRACT FROM AUTHOR]

Despite advances in diagnosis and treatment, racial disparities continue to exist in colorectal cancer (CRC) survival. This study aims to characterize the CRC survival differences among racial and ethnic minority groups. The Surveillance, Epidemiology, and End Results (SEER) database was used to identify adults diagnosed with CRC from 2015 to 2019. Demographics, disease characteristics, surgical treatment, stages, and survival data for individuals who are Hispanic, Black, Southeast Asian, Chinese, American Indian and Alaskan Native (AIAN), Asian Indian and Pakistani (AIP), and Native Hawaiian and Other Pacific Islanders (NHOPI) were extracted. Survival analysis was done using the Kaplan-Meier survival curve. Multivariate analysis was done with the Cox proportional hazard model. There were 40 091 individuals with CRC. NHOPI had the youngest median age of 59 years, while Chinese individuals had the oldest median age of 65 years. From the total sample of their respective subgroups, 43.8% of Black patients and 36.7% of AIAN patients had a median household income of <$60 000, while 55.3% of Southeast Asian patients, 59.7% of Chinese patients, 55.8% of AIP patients, and 65.6% of NHOPI patient had a median household income >$70 000. The 1-year survival rate was lower for patients who were Hispanic (62.0%), Black (60.9%), and AIAN (63.1%). Even after multivariate analysis, Black patients had a significant hazard ratio (HR) of 1.21 (95% confidence interval [95% CI]: 1.05-1.38), while AIP had a HR of 0.68 (95% CI 0.55-0.84), compared to AIAN. Other significant variables that were linked with survival included older age, advanced stage of CRC, a median household income <$60 000, male sex, no surgery, subtotal colectomy/hemicolectomy, and total colectomy. Further studies are needed to elucidate the specific causes of these differences and create appropriate strategies to reduce this survival disparity. [ABSTRACT FROM AUTHOR]

Colonoscopy often is recommended after an episode of diverticulitis to exclude missed colorectal cancer (CRC). This is a controversial recommendation based on limited evidence. We estimated the prevalence and odds of CRC and advanced colorectal neoplasia on colonoscopy in patients with diverticulitis compared with CRC screening. Using data from the Gastrointestinal Quality Improvement Consortium registry, we performed a cross-sectional study with patients ≥40 years old undergoing outpatient colonoscopy for an indication of diverticulitis follow-up evaluation or CRC screening. The primary outcome was CRC. The secondary outcome was advanced colorectal neoplasia. Odds ratios (ORs) and 95% CIs were calculated. We identified 4,591,921 outpatient colonoscopies performed for screening and 91,993 colonoscopies for diverticulitis follow-up evaluation. CRC prevalence was 0.33% in colonoscopies for screening and 0.31% in colonoscopies for diverticulitis. Compared with screening, patients with diverticulitis were less likely to have CRC (adjusted OR, 0.84; 95% CI, 0.74–0.94). CRC prevalence decreased to 0.17% in colonoscopies performed for diverticulitis only. Compared with screening, patients with diverticulitis as the only indication were less likely to have CRC (adjusted OR, 0.49; 95% CI, 0.36–0.68). CRC prevalence increased to 1.43% in patients with complicated diverticulitis. Compared with screening, patients with complicated diverticulitis were more likely to have CRC (adjusted OR, 3.57; 95% CI, 1.59–8.01). The risk of CRC cancer is low in most patients with diverticulitis. Patients with complicated diverticulitis are the exception. Our results suggest that colonoscopy to detect missed CRC should include diverticulitis patients with a complication and those not current with CRC screening. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer, a prevalent gastrointestinal carcinoma, has a high risk for recurrence when locally advanced and remains lethal when in an advanced stage. Prognostic biomarkers may help in better delineating the aggressiveness of this disease in individual patients and help to tailor appropriate therapies. CDX2, a transcription factor of gastrointestinal differentiation, has been proposed as a biomarker for good outcomes and could also be a marker of specific sub-types amenable to targeted therapies. Methods: Colorectal cancers from The Cancer Genome Atlas (TCGA) colorectal cohort and colon cancers from the Sidra-LUMC AC-ICAM cohort were categorized according to their expressions of CDX2 mRNA. Groups with CDX2 suppression were compared with cancers showing no suppression regarding their clinical and genomic characteristics. Results: CDX2-suppressed colorectal cancers showed a high prevalence of Microsatellite Instability (MSI) and a lower prevalence of chromosomal Instability (CIN) compared to non-CDX2-suppressed cancers. In addition, CDX2-suppressed cancers had a higher prevalence of mutations in several receptor tyrosine kinase genes, including EGFR, ERBB3, ERBB4, RET, and ROS1. In contrast, CDX2-suppressed cancers displayed lower mutation frequencies than non-CDX2-suppressed cancers in the genes encoding for the two most frequently mutated tumor suppressors, APC and TP53, and the most frequently mutated colorectal cancer oncogene, KRAS. However, CDX2-suppressed colorectal cancers had a higher prevalence of mutations in alternative genes of the WNT/APC/β-catenin and KRAS/BRAF/MEK pathways. In addition, they showed frequent mutations in DNA damage response (DDR) genes, such as BRCA2 and ATM. Conclusion: CDX2-suppressed colorectal cancers constitute a genomically distinct subset of colon and rectal cancers that have a lower prevalence of KRAS, APC, and TP53 mutations, but a high prevalence of mutations in less commonly mutated colorectal cancer genes. These alterations could serve as targets for personalized therapeutics in this subset. [ABSTRACT FROM AUTHOR]

Background: It is projected that, by 2040, the number of new cases of colorectal cancer (CRC) will increase to 3.2 million, and the number of deaths to 1.6 million, highlighting the need for prevention strategies, early detection and adequate follow-up. In this study, we aimed to provide an overview of the progress in personalized medicine of CRC in Serbia, with results and insights from the Institute for Oncology and Radiology of Serbia (IORS), and to propose guidance for tackling observed challenges in the future. Methods: Epidemiological data were derived from official global and national cancer registries and IORS electronic medical records. Germline genetic testing for Lynch syndrome was performed by Next Generation Sequencing. RAS and BRAF mutation analyses were performed using qPCR diagnostic kits. Results: Epidemiology and risk factors, prevention and early detection programs, as well as treatment options and scientific advances have been described in detail. Out of 103 patients who underwent germline testing for Lynch syndrome, 19 (18.4%) showed a mutation in MMR genes with pathogenic or likely pathogenic significance and 8 (7.8%) in other CRC-associated genes (APC, CHEK2, MUTYH). Of 6369 tested patients, 50.43% had a mutation in KRAS or NRAS genes, while 9.54% had the V600 mutation in the BRAF gene. Conclusions: Although significant improvements in CRC management have occurred globally in recent years, a strategic approach leading to population-based systemic solutions is required. The high incidence of young-onset CRC and the growing elderly population due to a rise in life expectancy will be especially important factors for countries with limited healthcare resources like Serbia. [ABSTRACT FROM AUTHOR]

Background: Colon cancer is the third most common type of cancer. High lymphovascular levels are linked to a number of cancers, including colon cancer, while lymph vascular invasion levels as a predictor of outcome are not well understood. Objective: Determine the influence of lymphovascular invasion on the recurrence of colon cancer. Patients and Methods: it was collected 126 colon cancer patients who had surgery and additional chemotherapy. The patients attended in the Baquba teaching hospital oncology centre and the Al Jawad oncology centre of Alkadhemiya hospital. Results: it was shown in this study that the high percentage ages of colon cancer patients was between 55-60 years, and there were more in women (57 %) than in men (43 %). The most common stage of the tumours was stage 3 (42.9 %), and in grade 2 (76.2 %). In terms of return, in this study, 71.4 % of people who had lymphovascular invasion positive and had a return of cancer in a percentage 73.3% of colon cancer patients. Conclusion: LVI plays an essential role for increasing recurrence of colon cancer, and there were a strong link between them. [ABSTRACT FROM AUTHOR]

Background and aims: Colorectal cancer is the third most common cancer worldwide, accounting for 10% of cancer deaths. Therefore, this study was performed with the aim of spatial analysis of risk factors for colorectal cancer in Iran. Method: This study was conducted ecologically using STEPS information (The WHO Stepwise Approach to NCD Risk Factor Surveillance) in Iran. To analyze the data, the researcher used cluster analysis and Geographically Weighted Regression methods with the help of ArcGIS version 10. Results: The results of OLS analysis showed that there was a significant relationship between tobacco consumption (B = 0.571, p‐value = 0.044) and smoking (B = 0.772, p‐value = 0.010) and the incidence of colon cancer (CC). There was also a significant relationship between abdominal obesity and the incidence of rectal cancer (RC) (B = 0.061, p‐value = 0.027). Conclusion: This study showed that (CC) high‐risk areas are located in central and northern parts of Iran, and the significant risk factors related to CC and RC were found to be tobacco use, cigarette smoking, and abdominal obesity. These findings are helpful to inform policymakers to plan screening services to reduce CC and RC, especially in high‐risk populations. [ABSTRACT FROM AUTHOR]

A novel bismuth(III) trifluoro‐methanesulfonate‐catalyzed and environmentally benign synthetic strategy for the construction of a wide range of structurally diverse, sophisticated [5,6,5]‐oxygen‐containing tricyclic frameworks with easy‐to handle propargylic alcohols and 2‐allylphenols as substrates in the presence of Bi(OTf)3 and AgOTf is described. This Lewis acid catalyzed [3+2] annulation protocol, which tolerates a great deal of functional groups, proceeds through a sequential Meyer‐Schuster rearrangement, nucleophilic substitution, 5‐exo‐trig cyclization, 5‐endo‐trig cyclization, and proton exchange sequences, affording a versatile approach for accessing oxygen‐containing tricyclic skeletons in moderate‐to‐excellent yields. In addition, most of the obtained compounds exhibited anti‐tumor activities against three types of human cancer cell lines in vitro, including Caco‐2 colon cancer cells, MCF‐7 breast cancer cells, and Hepg‐2 liver cancer cells. [ABSTRACT FROM AUTHOR]

Chronic inflammation is a factor in the development of cancer, and probiotics play a role in preventing or treating inflammation as an adjuvant therapy. To investigate potential probiotics for the prevention of colitis-associated colorectal cancer (CAC), Bifidobacterium bifidum H3-R2 and Lactococcus lactis KLDS4.0325 were used to examine the effects on colon cancer cells and in an inflammation-related cancer animal model. The results revealed that B. bifidum H3-R2 in combination with L. lactis KLDS4.0325 caused apoptosis in colon cancer cells by increasing caspase-3 and caspase-9 protein levels, enhancing Bax expression, and lowering Bcl-2 expression. In addition, the combination of the two strains relieved the tissue damage; reduced proinflammatory cytokines, myeloperoxidase (MPO) activity, and hypoxia-inducible factor 1-alpha (HIF-1α) level; upregulated anti-inflammatory cytokines; increased colonic tight junction protein expression; regulated intestinal homeostasis by inhibiting NLRP3 inflammasome signaling pathway; and improved the imbalance of gut microbiota in animal models. Moreover, the combination of the two strains had a greater preventive impact than each strain alone. These findings are supportive of clinical studies and product development of multi-strain probiotic preparations for diseases associated with colitis. [ABSTRACT FROM AUTHOR]

Background: Different detection platforms can lead to significant differences in the results of CA19-9. Here, a case of a 38-year-old male colon cancer patient who underwent CA19-9 testing on two platforms after surgery. Methods: We first inspect the instrument to confirm its normal operation and good indoor quality control. Then, we conduct dilution experiments to eliminate interference from heterophilic antibodies, compare and analyze inherent differences with other platforms, and regularly follow up to dynamically monitor the patient's condition. Results: During follow-up, the patient's CA19-9 levels rose consistently on both platforms, leading to tumor recurrence two years later, missing optimal treatment. Conclusions: Dynamic monitoring of tumor markers should be based on a stable platform and combined with imaging examinations. For abnormal elevated results, humanistic care is needed to address the patient's fear and doubts about the test results. [ABSTRACT FROM AUTHOR]

Cancer poses a significant threat due to its aggressive nature, potential for widespread metastasis, and inherent heterogeneity, which often leads to resistance to chemotherapy. Lung cancer ranks among the most prevalent forms of cancer worldwide, affecting individuals of all genders. Timely and accurate lung cancer detection is critical for improving cancer patients’ treatment outcomes and survival rates. Screening examinations for lung cancer detection, however, frequently fall short of detecting small polyps and cancers. To address these limitations, computer-aided techniques for lung cancer detection prove to be invaluable resources for both healthcare practitioners and patients alike. This research implements an enhanced EfficientNetB1 deep learning model for accurate detection and classification using histopathological images. The proposed technique accurately classifies the histopathological images into three distinct classes: (1) no cancer (benign), (2) adenocarcinomas, and (3) squamous cell carcinomas. We evaluated the performance of the proposed technique using the histopathological (LC25000) lung dataset. The preprocessing steps, such as image resizing and augmentation, are followed by loading a pretrained model and applying transfer learning. The dataset is then split into training and validation sets, with fine-tuning and retraining performed on the training dataset. The model’s performance is evaluated on the validation dataset, and the results of lung cancer detection and classification into three classes are obtained. The study’s findings show that an enhanced model achieves exceptional classification accuracy of 99.8%. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests that deregulated RNA splicing factors play critical roles in tumorigenesis; however, their specific involvement in colon cancer remains largely unknown. Here we report that the splicing factor RBM25 is overexpressed in colon cancer, and this increased expression correlates with a poor prognosis of patients with colon cancer. Functionally, RBM25 ablation suppresses the growth of colon cancer cells both in vitro and in vivo. Mechanistically, our transcriptome-wide analysis of splicing events revealed that RBM25 regulates a large number of cancer-related alternative splicing events across the human genome in colon cancer. Particularly, RBM25 regulates the splicing of MNK2 by interacting with the poly G rich region in exon 14a, thereby inhibiting the selection of the proximal 3′ splice site (ss), resulting in the production of the oncogenic short isoform, MNK2b. Knockdown of RBM25 leads to an increase in the MNK2a isoform and a decrease in the MNK2b isoform. Importantly, re-expression of MNK2b or blocking the 3′ ss of the alternative exon 14a with ASO partially reverses the RBM25 knockdown mediated tumor suppression. Moreover, MNK2b levels were significantly increased in colon cancer tissues, which is positively correlated with the expression level of RBM25. Collectively, our findings uncover the critical role of RBM25 as a key splicing factor in colon cancer, suggesting its potential as a prognostic marker and therapeutic target. [ABSTRACT FROM AUTHOR]

Triptolide (TPL), a natural product extracted from Tripterygium wilfordii Hook F, exerts potential anti‐cancer activity. Studies have shown that TPL is involved in multiple cellular processes and signal pathways; however, its pharmaceutical activity in human colorectal cancer (CRC) as well as the underlying molecular mechanism remain elusive. In this study, the effects of TPL on HCT116 human colon cancer cells and CCD841 human colon epithelial cells are first evaluated. Next, the protein targets of TPL in HCT116 cells are identified through an activity‐based protein profiling approach. With subsequent in vitro experiments, the mode of action of TPL in HCT116 cells is elucidated. As a result, TPL is found to selectively inhibit HCT116 cell viability and migration. A total of 54 proteins are identified as the targets of TPL in HCT116 cells, among which, Annexin A1 (ANXA1) and Peroxiredoxin I/II (Prdx I/II) are picked out for further investigation due to their important role in CRC. The interaction between TPL and ANXA1 or Prdx I is confirmed, and it is discovered that TPL exerts inhibitory effect against HCT116 cells through binding to ANXA1 and Prdx I. The study reinforces the potential of TPL in the CRC therapy, and provides novel therapeutic targets for the treatment of CRC. [ABSTRACT FROM AUTHOR]

Corosolic acid (CA) is a well-known natural pentacyclic triterpene found in numerous therapeutic plants that can exhibit many bioactivities including anti-inflammatory and anti-tumor actions. The current investigation explores the chemoprotective roles of CA against azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in rats. Thirty Sprague Dawley rats were grouped in 5 cages; Group A, normal control rats inoculated subcutaneously (sc) with two doses of normal saline and fed orally on 10% tween 20; Groups B-E received two doses (sc) of azoxymethane in two weeks and treated with either 10% tween 20 (group B) or two intraperitoneal injections of 35 mg/kg 5-fluorouracil each week for one month (group C), while group D and E treated with 30 and 60 mg/kg, respectively, for 2 months. The toxicity results showed lack of any behavioral abnormalities or mortality in rats ingested with up-to 500 mg/kg of CA. The present AOM induction caused a significant initiation of ACF characterized by an increased number, larger in size, and well-matured tissue clusters in cancer controls. AOM inoculation created a bizarrely elongated nucleus, and strained cells, and significantly lowered the submucosal glands in colon tissues of cancer controls compared to 5-FU or CA-treated rats. CA treatment led to significant suppression of ACF incidence, which could be mediated by its modulatory effects on the immunohistochemical proteins (pro-apoptotic (Bax) and reduced PCNA protein expressions in colon tissues). Moreover, CA-treated rats had improved oxidative stress-mediated cytotoxicity indicated by increased endogenous antioxidants (SOD and CAT) and reduced lipid peroxidation indicators (MDA). In addition, CA ingestion (30 and 60 mg/kg) suppressed the inflammatory cascades, indicated by decreased serum TNF-α and IL-6 cytokines and increased anti-inflammatory (IL-10) cytokines consequently preventing further tumor development. CA treatment maintained liver and kidney functions in rats exposed to AOM cytotoxicity. CA could be a viable alternative for the treatment of oxidative-related human disorders including ACF. [ABSTRACT FROM AUTHOR]

The malignant behavior and immune escape ability of cancer cells lead to therapeutic failure and poor prognosis for patients with various cancers, including colon cancer. Plexin domain containing 1 (PLXDC1) was initially identified to exert key roles in tumor by regulating angiogenesis and has recently proved to be involved in cell proliferation and migration of glioblastoma and gastric cancer cells. However, its roles in colon cancer remain unclear. In this study, the online bioinformatics databases confirmed high expression of PLXDC1 in colon cancer specimens, which was associated with cancer stages and nodal metastasis. Similarly, the increased expression of PLXDC1 was also validated in our collected samples and colon cancer cells. Moreover, patients with high expression of PLXDC1 had shorter survival, indicating that PLXDC1 might be a potential prognostic predictor for colon cancer patients. Notably, targeting PLXDC1 inhibited cancer cell viability and invasion, and enhanced cell apoptosis. Intriguingly, Tumor Immune Estimation Resource database confirmed that PLXDC1 expression was related to various tumor‐infiltrating immune cells in colon adenocarcinoma including macrophages, and its expression was also correlated with M2‐like macrophage markers. In vitro, colon cancer cells with PLXDC1 downregulation had a reduced ability to recruit and polarize macrophage towards M2 phenotype by decreasing the percentage of CD206+ cells and M2‐like markers (CD206, CD163, arginase1, and interleukin 10 [IL‐10]). Moreover, PLXDC1 knockdown attenuated M2 macrophage‐mediated promotion in cancer cell viability and invasion. Mechanically, inhibition of PLXDC1 suppressed activation of the IL‐6/Signal transducer and activator of transcription 3 (STAT3) signaling. Reactivating the above pathway by transfection with IL‐6 plasmids reversed the suppressive effects of PLXDC1 knockdown on cancer cell malignant behaviors, macrophage recruitment and M2‐like polarization. Thus, PLXDC1 downregulation may inhibit the malignancy of colon cancer cells and their ability to recruit and polarize macrophages towards M2 phenotype by blocking the IL‐6/STAT3 pathway. Together, targeting PLXDC1 may attenuate the progression of colon cancer by direct roles in cancer cells and indirect roles in macrophage polarization, representing a promising therapeutic target for colon cancer patients. [ABSTRACT FROM AUTHOR]

Despite breakthroughs in the development of cancer diagnosis and therapy, most current therapeutic approaches lack precise specificity and sensitivity, resulting in damage to healthy cells. Selective delivery of anti-cancer agents is thus an important goal of cancer therapy. Scorpion venom (SV) and/or body parts have been used since early civilizations for medicinal purposes, and in cultures, SV is still applied to the treatment of several diseases including cancer. SV contains numerous active micro and macromolecules with diverse pharmacological effects. These include potent anti-microbial, anti-viral, anti-inflammatory, and anti-cancer properties. This review focuses on the recent advances of SV-derived peptides as promising anti-cancer agents and their diagnostic and therapeutic potential applications in cancers such as glioma, breast cancer, prostate cancer, and colon cancer. Well-characterized SV-derived peptides are thus needed to serve as potent and selective adjuvant therapy for cancer, to significantly enhance the patients' survival and wellbeing. [ABSTRACT FROM AUTHOR]

Background: The Naples prognostic score (NPS) determined by the nutritional and inflammatory condition of an individual is attracting growing attention for predicting postoperative outcomes in a variety of malignancies. The study aimed to assess the clinical significance of a modified NPS (M-NPS) and establish and validate nomograms incorporating M-NPS in curative stage II-III colon cancer patients. Methods: We retrospectively analyzed 328 stage II-III colon cancer patients receiving radical surgical resection at our hospital from January 2011 to December 2016. Kaplan–Meier (KM) survival analysis and Cox regression analysis were executed for overall survival (OS) and cancer-specific survival (CSS). Independent predictive indicators were applied to develop nomograms. The model’s performance was evaluated using many different methods. Results: Of a total of 328 cases, 153 cases were in group 0, 145 in group 1, and 30 in group 2. In terms of OS or CSS, there were obvious differences between groups 0 and 1, and between groups 0 and 2. Age, obstruction, N stage, gross tumor type, and M-NPS group were independent prognostic indicators for OS, while obstruction, gross tumor type, M-NPS group, and N stage were independent predictive parameters for CSS. Furthermore, the training and validation sets were randomly allocated among a cohort of 328 patients. OS and CSS prediction nomograms were developed. In the training and validation cohort, the C-index and ROC analysis showed good discrimination, calibration curves exhibited an excellent level of consistency between model-predicted survival and actual survival outcomes, and DCA curves demonstrated good clinical performance. Conclusion: M-NPS is a reliable survival predictor in patients with curative stage II-III colon cancer. Nomograms incorporating M-NPS for OS and CSS have good predictive performance and clinical utility. [ABSTRACT FROM AUTHOR]

Background and aim: Colorectal cancer is a prevalent malignancy worldwide, and right hemicolectomy is a common surgical procedure for its treatment. However, postoperative incisional infections remain a significant complication, leading to prolonged hospital stays, increased healthcare costs, and patient discomfort. Therefore, this study aims to utilize machine learning models, including random forest, support vector machine, deep learning models, and traditional logistic regression, to predict factors associated with incisional infection following right hemicolectomy for colon cancer. Methods: Clinical data were collected from 322 patients undergoing right hemicolectomy for colon cancer, including demographic information, preoperative chemotherapy status, body mass index (BMI), operative time, and other relevant variables. These data are divided into training and testing sets in a ratio of 7:3. Machine learning models, including random forest, support vector machine, and deep learning, were trained using the training set and evaluated using the testing set. Results: The deep learning model exhibited the highest performance in predicting incisional infection, followed by random forest and logistic regression models. Specifically, the deep learning model demonstrated higher area under the receiver operating characteristic curve (ROC-AUC) and F1 score compared to other models. These findings suggest the efficacy of machine learning models in predicting risk factors for incisional infection following right hemicolectomy for colon cancer. Conclusions: Machine learning models, particularly deep learning models, offer a promising approach for predicting the risk of incisional infection following right hemicolectomy for colon cancer. These models can provide valuable decision support for clinicians, facilitating personalized treatment strategies and improving patient outcomes. [ABSTRACT FROM AUTHOR]

Capecitabine is recommended as one of the first-line chemotherapy treatments for advanced or metastatic colorectal cancer. Researches have been conducted on capecitabine's impact on the viability of human colon cancer cells and its potential to induce apoptosis. However, even in cases initially responsive to treatment, the development of acquired resistance significantly limits its efficacy. Challenges still exist in effectively treating patients with chemotherapy, and developing new cytotoxic drugs is hindered by drug resistance. Fisetin alters the cell cycle, inducing apoptosis, inhibiting cancer cell proliferation, and enhancing the therapeutic effectiveness of chemotherapy drugs. This work aims to create a plan for reversing capecitabine resistance. For this purpose, the role of capecitabine and/or fisetin combinations in cell proliferation and apoptosis has been determined in both wild-type and capecitabine-resistant HT29 cells (CR/HT29). We developed capecitabine-resistant cell line from wild-type HT29 cells. This study demonstrated the effects of capecitabine, fisetin, and their combinations on both resistant and wild-type cells through experiments including cell survival skills, cell proliferation, wound healing, colony formation, hoechst staining, and western blot analysis. We established capecitabine-resistant cell lines. P-gp expression increased in CR/HT29 cells. Capecitabine effects on a CR/HT29 cells less than wild-type HT29 cells. The combination of fisetin and capecitabine in cell proliferation caused greater reductions in wild-type HT29 cells than in capecitabine-resistant cells. Fisetin has also additive effects on the apoptotic pathway in CR/HT29 cells. This study provides new perspectives on the combination of capecitabine and/or flavonoid treatment in resistant cells. [ABSTRACT FROM AUTHOR]

Colorectal cancer, recognized as a quintessential age-related disease, underscores the intricate interplay between aging mechanisms and disease pathogenesis. Cellular senescence, a DNA damage-induced cellular stress response, is characterized by cell cycle arrest, the expression of an inflammatory senescence-associated secretory phenotype, and alterations in extracellular matrix metabolism. It is widely recognized as a fundamental and evolutionarily conserved mechanism of aging. Guided by geroscience principles, which assert that the pathogenesis of age-related diseases involves cellular mechanisms of aging, this study delves into the role of senescence-related genes in colon cancer progression. Leveraging a gene set reflective of senescence-associated pathways, we employed uni- and multivariate Cox proportional hazards survival analysis combined with the determination of the false discovery rate to analyze correlations between gene expression and survival. The integrated database of 1130 colon cancer specimens with available relapse-free survival time and relapse event data from ten independent cohorts provided a robust platform for survival analyses. We identified senescence-related genes associated with differential expression levels linked to shorter survival. Our findings unveil a prognostic signature utilizing cellular senescence-related genes (hazard ratio: 2.73, 95% CI 2.12–3.52, p = 6.4E − 16), offering valuable insights into survival prediction in colon cancer. Multivariate analysis underscored the independence of the senescence-related signature from available epidemiological and pathological variables. This study highlights the potential of senescence-related genes as prognostic biomarkers. Overall, our results underscore the pivotal role of cellular senescence, a fundamental mechanism of aging, in colon cancer progression. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most frequently occurring cancers, but prognostic biomarkers identifying patients at risk of recurrence are still lacking. In this study, we aimed to investigate in more detail the spatial relationship between intratumoural T cells, cancer cells, and cancer cell hallmarks as prognostic biomarkers in stage III colorectal cancer patients. We conducted multiplexed imaging of 56 protein markers at single‐cell resolution on resected fixed tissue from stage III CRC patients who received adjuvant 5‐fluorouracil (5FU)‐based chemotherapy. Images underwent segmentation for tumour, stroma, and immune cells, and cancer cell 'state' protein marker expression was quantified at a cellular level. We developed a Python package for estimation of spatial proximity, nearest neighbour analysis focusing on cancer cell–T‐cell interactions at single‐cell level. In our discovery cohort (Memorial Sloan Kettering samples), we processed 462 core samples (total number of cells: 1,669,228) from 221 adjuvant 5FU‐treated stage III patients. The validation cohort (Huntsville Clearview Cancer Center samples) consisted of 272 samples (total number of cells: 853,398) from 98 stage III CRC patients. While there were trends for an association between the percentage of cytotoxic T cells (across the whole cancer core), it did not reach significance (discovery cohort: p = 0.07; validation cohort: p = 0.19). We next utilised our region‐based nearest neighbour approach to determine the spatial relationships between cytotoxic T cells, helper T cells, and cancer cell clusters. In both cohorts, we found that shorter distance between cytotoxic T cells, T helper cells, and cancer cells was significantly associated with increased disease‐free survival. An unsupervised trained model that clustered patients based on the median distance between immune cells and cancer cells, as well as protein expression profiles, successfully classified patients into low‐risk and high‐risk groups (discovery cohort: p = 0.01; validation cohort: p = 0.003). © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC)-a malignant growth in the colon or rectum-is the second largest cause of cancer deaths worldwide. Early detection may increase therapy choices. Deep learning can improve early medical detection to reduce the risk of unintentional death from an incorrect clinical diagnosis. Histopathological examination of colon cancer is essential in medical research. This paper proposes a deep learning-based colon cancer detection method using stainnormalized images. We use deep learning methods to improve detection accuracy and efficiency. Our solution normalizes image stain variations and uses deep learning models for reliable classification. This research improves colon cancer histopathology analysis, which may enhance diagnosis. Our paper uses DenseNet-121, VGG-16, GoogLeNet, ResNet-50, and ResNet-18 deep learning models. We also analyze how stain normalization (SN) improves our model on histopathology images. The ResNet-50 model with SN yields the highest values (9.94%) compared to the other four models and the nine models from previous studies. [ABSTRACT FROM AUTHOR]

Background: There is mounting evidence that microscopically positive (R1) margins in patients with colorectal cancer (CRC) may represent a surrogate for aggressive cancer biology rather than technical failure during surgery. However, whether detectable biological differences exist between CRC with R0 and R1 margins is unknown. We sought to investigate whether mismatch repair (MMR) status differs between Stage III CRC with R0 or R1 margins. Methods: Patients treated for Stage III CRC from January 1, 2016 to December 31, 2019 were identified by using the Danish Colorectal Cancer Group database. Patients were stratified according to MMR status (proficient [pMMR] vs. deficient [dMMR]) and margin status. Outcomes of interest included the R1 rate according to MMR and overall survival. Results: A total of 3636 patients were included, of whom 473 (13.0%) had dMMR colorectal cancers. Patients with dMMR cancers were more likely to be elderly, female, and have right-sided cancers. R1 margins were significantly more common in patients with dMMR cancers (20.5% vs. 15.2%, p < 0.001), with the greatest difference seen in the rate of R1 margins related to the primary tumour (8.9% vs. 4.7%) rather than to lymph node metastases (11.6% vs. 10.5%). This association was seen in both right- and left-sided cancers. On multivariable analyses, R1 margins, but not MMR status, were associated with poorer survival, alongside age, pN stage, perineural invasion, and extramural venous invasion. Conclusions: In patients with Stage III CRC, dMMR status is associated with increased risks of R1 margins following potentially curative surgery, supporting the use of neoadjuvant immunotherapy in this patient group. [ABSTRACT FROM AUTHOR]

In this study, the anticancer effect of doenjang according to the type of salt was investigated. Three samples were prepared: doenjang made with purified salt, doenjang made with generally manufactured solar salt, and doenjang made with washed and dehydrated solar salt (WDSD). In mice in which colon cancer was induced with azoxymethane/dextran sodium sulfate, doenjang made with solar salt, especially doenjang made with washed and dehydrated solar salt, was found to have a much higher colon cancer inhibition effect. WDSD significantly promoted the mRNA expression of apoptosis-related factors such as Bcl-2–associated X protein (Bax) and caspase 9 and the cell cycle arrest-related factors p53 and p21, and conversely significantly reduced the mRNA expression of apoptosis inhibitors such as B-cell lymphoma-2 (Bcl-2) (p < 0.05). Additionally, metabolites were investigated to determine which substances in WDSD exhibit this anticancer effect. As a result, the contents of isoflavone and soyasaponin B in the form of aglycons such as genistein, daidzein, and glycitein, which are known to have anticancer and anti-inflammatory properties, were found to be significantly high. Therefore, the results confirmed that doenjang prepared with washed and dehydrated solar salt has superior anticancer potential against colon cancer, and that various active ingredients contribute to the improvement of this functionality. [ABSTRACT FROM AUTHOR]

In various countries worldwide, the incidence of colon cancer-related deaths has been on the rise in recent years. Early detection of symptoms and identification of intestinal polyps are crucial for improving the cure rate of colon cancer patients. Automated computer-aided diagnosis (CAD) has emerged as a solution to the low efficiency of traditional methods relying on manual diagnosis by physicians. Deep learning is the latest direction of CAD development and has shown promise for colonoscopic polyp segmentation. In this paper, we present a multi-level encoder-decoder architecture for polyp segmentation based on the Transformer architecture, termed NA-SegFormer. To improve the performance of existing Transformer-based segmentation algorithms for edge segmentation on colon polyps, we propose a patch merging module with a neighbor attention mechanism based on overlap patch merging. Since colon tract polyps vary greatly in size and different datasets have different sample sizes, we used a unified focal loss to solve the problem of category imbalance in colon tract polyp data. To assess the effectiveness of our proposed method, we utilized video capsule endoscopy and typical colonoscopy polyp datasets, as well as a dataset containing surgical equipment. On the datasets Kvasir-SEG, Kvasir-Instrument and KvasirCapsule-SEG, the Dice score of our proposed model reached 94.30%, 94.59% and 82.73%, with an accuracy of 98.26%, 99.02% and 81.84% respectively. The proposed method achieved inference speed with an Frame-per-second (FPS) of 125.01. The results demonstrated that our suggested model effectively segmented polyps better than several well-known and latest models. In addition, the proposed method has advantages in trade-off between inference speed and accuracy, and it will be of great significance to real-time colonoscopic polyp segmentation. The code is available at https://github.com/promisedong/NAFormer. [ABSTRACT FROM AUTHOR]

Background: Bufalin (BA) is a potent traditional Chinese medicine derived from toad venom. It has shown significant antitumor activity, but its use is limited by cardiotoxicity, which necessitates innovative delivery methods, such as rod-shaped mesoporous silica nanoparticles (rMSNs). rMSNs have been extensively employed for reducing drug toxicity and for controlled or targeted drug delivery in tumor therapy. However, their potential in delivering BA has not been completely elucidated. Therefore, in this study, BA-loaded rMSNs (BA-rMSNs) were developed to investigate their potential and mechanism in impairing colon cancer cells. Methods: rMSNs were developed via the sol‒gel method. Drug encapsulation efficiency and loading capacity were determined to investigate the advantages of the rMSN in loading BA. The antiproliferative activities of the BA-rMSNs were investigated via 5-ethynyl-2'-deoxyuridine and CCK-8. To evaluate cell death, Annexin V-APC/PI apoptotic and calcein-AM/PI double staining were performed. Western blotting, oil red O staining, and Nile red solution were employed to determine the ability of BA-rMSNs to regulate lipophagy. Results: The diameter of the BA-rMSNs was approximately 60 nm. In vitro studies demonstrated that BA-rMSNs markedly inhibited HCT 116 and HT-29 cell proliferation and induced cell death. In vivo studies revealed that BA-rMSNs reduced BA-mediated cardiotoxicity and enhanced BA tumor targeting. Mechanistic studies revealed that BA-rMSNs blocked lipophagy. Conclusions: rMSNs reduced BA-mediated cardiotoxicity and impaired the growth of colon cancer cells. Mechanistically, antitumor activity depends on lipophagy. [ABSTRACT FROM AUTHOR]

Background: Gastroparesis is a major complication following complete mesocolic excision (CME) and significantly impacts patient outcomes. This study aimed to create a machine learning model to pinpoint key risk factors before, during, and after surgery, effectively predicting the risk of gastroparesis after CME. Methods: The study involved 1146 patients with colon cancer, out of which 95 developed gastroparesis. Data were collected on 34 variables, including demographics, chronic conditions, pre-surgery test results, types of surgery, and intraoperative details. Four machine learning techniques were employed: extreme gradient boosting (XGBoost), random forest (RF), support vector machine (SVM), and k-nearest neighbor (KNN). The evaluation involved k-fold cross-validation, receiver operating characteristic (ROC) analysis, calibration curves, decision curve analysis (DCA), and external validation. Results: XGBoost excelled in its performance for predictive models. ROC analysis showed high accuracy for XGBoost, with area under the curve (AUC) scores of 0.976 for the training set and 0.906 for the validation set. K-fold cross-validation confirmed the model's stability, and calibration curves indicated high predictive accuracy. Additionally, DCA highlighted XGBoost's superior patient benefits for intervention treatments. An AUC of 0.77 in external validation demonstrated XGBoost's strong generalization ability. Conclusion: The XGBoost-fueled predictive model for post-surgery colon cancer patients proved highly effective. It underlined gastroparesis as a significant post-operative issue, associated with advanced age, prolonged surgeries, extensive intraoperative blood loss, surgical techniques, low serum protein levels, anemia, diabetes, and hypothyroidism. [ABSTRACT FROM AUTHOR]

Photothermal immunotherapy emerges as a promising strategy for treating tumors. However, the majority of current photothermal immunotherapy approaches do not yet show significant potential for clinical translation. In this study, lyophilized polydopamine (PDA) nanoparticles combined with Bacillus Calmette–Guérin (BCG) are investigated for photothermal immunotherapy against colorectal cancer. By simply mixing with two lyophilized powders, PDA nanoparticles can covalently bond onto BCG to form BCG@PDA. This combination demonstrates a potent photothermal cytotoxic effect on tumor cells by utilizing PDA nanoparticles. In addition, a heightened immune response triggered by the BCG vaccine, as evidenced by the secretion of important pro‐inflammatory cytokines and the activation of antigen‐presenting cells, is observed. In vivo testing on a murine colon cancer model demonstrates that the combined treatment significantly inhibits tumor growth. Further, the lyophilized PDA nanoparticles can be stored at −20 °C for up to 1 year with stable photothermal properties. Therefore, this study not only presents a reliable method for storing the therapeutic PDA nanoparticles but also demonstrates the potential application of BCG@PDA in photothermal immunotherapy for colorectal cancer. [ABSTRACT FROM AUTHOR]

AbstractIntroductionMaterial and methodsResultsConclusionsComplete mesocolic excision (CME) is widely adopted for its assumed superior oncological outcome. However, it’s unclear if all right-sided colon cancer patients benefit from CME. The aim of this systematic review is to investigate whether CME contributes to postoperative outcomes and to determine the surgical indications for CME.We searched eligible articles about CME versus non-CME procedures for right-sided colon cancer in the OVID Medline, Embase, and Cochrane CENTRAL databases, and a meta-analysis was conducted.Twenty-two articles and seven abstracts involving 8088 patients were included in this study. Among them, 3803 underwent CME and 4285 non-CME procedures. The analysis showed that CME was favoured for three-year disease-free survival (DFS) and overall survival (OS), for local, systemic, and total recurrence, and for hospital stay durations. However, increased vascular injury and longer surgery time were observed in CME. Regarding the three-year OS, the superiority of CME was observed only in Stage III. Additionally, no significant differences were observed between CME and non-CME groups regarding overall complications, 30-day readmission rates, reoperation, or postoperative mortality rates.CME for right-sided colon cancer should be considered, particularly in Stage III patients, to contribute to improved oncological outcomes. However, careful attention must be paid to the increased risk of vascular injury. [ABSTRACT FROM AUTHOR]

A series of lupane‐type A‐ring azepanes modified at the C28, C30 positions and NH‐group have been synthesized and evaluated for cytotoxic activity against the NCI‐60 cancer cell line panel. Azepano‐betulinic amides showed pronounced activity, with a GI50 range from 0.57 μM to 14.30 μM, being 4–5 times more active than doxorubicin against colon cancer HCT‐15 and ovarian cancer NCI/ADR‐RES. It was established that azepano‐betulinic cyclohexyl‐amide acts preferentially through apoptosis induction both in conditionally normal and tumor cells, demonstrating mainly cytotoxic properties, whereas earlier studied azepano‐betulin acted by triggering the cell cycle arrest in cancerous cells and displayed mostly cytostatic activity. The crystal structure of N‐methyl‐azepano‐betulin hydrochloride salt was established by X‐ray diffraction method. [ABSTRACT FROM AUTHOR]

Background: Several methods are used for reconstruction in colon cancer surgery, including hand-sewn or stapled anastomosis. However, few reports have compared short-term outcomes among reconstruction methods. This study compared short-term outcomes between delta-shaped anastomosis (Delta) and functional end-to-end anastomosis (FEEA). Methods: We retrospectively reviewed 1314 consecutive patients who underwent colorectal surgery with FEEA or Delta reconstruction between January 2016 and December 2023. Patients were divided into two groups according to reconstruction by FEEA (F group; n = 1242) or Delta (D group; n = 72). Propensity score matching was applied to minimize the possibility of selection bias and to balance covariates that could affect postoperative complications. Short-term outcomes were compared between groups. Results: Postoperative complications occurred in 215 patients (17.3%) in F group and 8 patients (11.1%) in D group. Before matching, transverse colon cancer was more frequent (p = 0.002), clinical N-positive status was less frequent (44.1% versus 16.7%, p < 0.001), distant metastasis was less frequent (11.7% versus 1.4%, p = 0.003), and laparoscopic approach was more frequent (87.8% versus 100%, p < 0.001) in D group. After matching, no differences in any clinical factor were evident between groups. Blood loss was significantly lower (28 mL versus 10 mL, p = 0.002) in D group, but operation time and postoperative complication rates were similar between groups. Conclusions: Delta and FEEA were both considered safe as reconstruction methods. Further studies are needed to clarify appropriate case selection for Delta and FEEA. [ABSTRACT FROM AUTHOR]