MiRNA expression affects survival in patients with obstructive sleep apnea and metastatic colorectal cancer.

Introduction: The relationship between obstructive sleep apnea (OSA) and cancer has been recognized for some time now. However, little is known about the mechanisms by which sleep apnea promotes tumorigenesis and the impact of OSA on survival after cancer diagnosis. In the last few years, research has focused on the exploration of different biomarkers to understand the mechanisms underlying this relationship and miRNAs, non-coding single strands of about 22 nucleotides that post-transcriptionally regulate gene expression, have emerged as possible actors of this process.The aim of the study was to evaluate the impact of OSA on survival of metastatic colorectal cancer (mCRC) patients based on the expression of specific miRNAs. Methods: The expression of 6 miRNAs, respectively miR-21, miR-23b, miR-26a, miR-27b, miR-145 and miR-210, was analyzed by qRT-PCR in patients' sera. Response to first-line therapy, Kaplan-Meier curves of overall and progression-free survival were used to evaluate survival in mCRC patients with and without OSA stratified for the expression of miRNAs. Results: The expression of miR-21, miR-23b, miR-26a and miR-210 was significantly upregulated in mCRCs with OSA compared to no OSA. In mCRC patients with OSA and increasing expression of miR-21, miR-23b, miR-26a and miR-210 risk of progression after first-line therapy was higher and both overall and progression-free survival were significantly worst. Conversely, as miR-27b and miR-145 expression increased, the life expectancy of patients diagnosed with OSA and mCRC improved markedly. Conclusions: This study highlights the relevance of specific miRNAs on OSA in mCRCs and their significance as non-invasive biomarkers in predicting the prognosis in patients with mCRC and OSA.

Tubeimoside-I, an inhibitor of HSPD1, enhances cytotoxicity of oxaliplatin by activating ER stress and MAPK signaling pathways in colorectal cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Tubeimoside-I (TBM) promotes various cancer cell death by increasing the reactive oxygen species (ROS) production. However, the specific molecular mechanisms of TBM and its impact on oxaliplatin-mediated anti-CRC activity are not yet fully understood. AIM OF THE STUDY: To elucidate the therapeutic effect and underlying molecular mechanism of TBM on oxaliplatin-mediated anti-CRC activity. MATERIALS AND METHODS: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, wound healing assays and flow cytometry were conducted to investigate the changes in cell phenotypes and ROS generation. Real-time quantitative PCR (qRT-PCR) and western blotting were performed to detect the expressions of related mRNA and proteins. Finally, mouse xenograft models demonstrated that synergistic anti-tumor effects of combined treatment with TBM and oxaliplatin. RESULTS: The synergistic enhancement of the anti-tumor effects of oxaliplatin in colon cancer cells by TBM involved in the regulation of ROS-mediated endoplasmic reticulum (ER) stress, C-jun-amino-terminal kinase (JNK), and p38 MAPK signaling pathways. Mechanistically, TBM increased ROS generation in colon cancer cells by inhibiting heat shock protein 60 (HSPD1) expression. Knocking down HSPD1 increased TBM-induced antitumor activity and ROS generation in colon cancer cells. The mouse xenograft tumor models further validated that the combination therapy exhibited stronger anti-tumor effects than monotherapy alone. CONCLUSIONS: Combined therapy with TBM and oxaliplatin might be an effective therapeutic strategy for some CRC patients.

Efficacy of texture and color enhancement imaging for the visibility and diagnostic accuracy of non-polypoid colorectal lesions.

Objective: A newly launched endoscopy system (EVIS X1, CV-1500; Olympus) is equipped with texture and color enhancement imaging (TXI). We aimed to investigate the efficacy of TXI for the visibility and diagnostic accuracy of non-polypoid colorectal lesions. Methods: We examined 100 non-polypoid lesions in 42 patients from the same position, angle, and distance of the view in three modes: white light imaging (WLI), narrow-band imaging (NBI), and TXI. The primary outcome was to compare polyp visibility in the three modes using subjective polyp visibility score and objective color difference values. The secondary outcome was to compare the diagnostic accuracy without magnification. Results: Overall, the visibility score of TXI was significantly higher than that of WLI (3.7 ± 1.1 vs. 3.6 ± 1.1; p = 0.008) and lower than that of NBI (3.7 ± 1.1 vs. 3.8 ± 1.1; p = 0.013). Color difference values of TXI were higher than those of WLI (11.5 ± 6.9 vs. 9.1 ± 5.4; p < 0.001) and lower than those of NBI (11.5 ± 6.9 vs. 13.1 ± 7.7; p = 0.002). No significant differences in TXI and NBI (visibility score: 3.7 ± 1.0 vs. 3.8 ± 1.1; p = 0.833, color difference values: 11.6 ± 7.1 vs. 12.9 ± 8.3; p = 0.099) were observed for neoplastic lesions. Moreover, the diagnostic accuracy of TXI was significantly higher than that of NBI (65.5% vs. 57.6%, p = 0.012) for neoplastic lesions. Conclusions: TXI demonstrated higher visibility than that of WLI and lower than that of NBI. Further investigations are warranted to validate the performance of the TXI mode comprehensively.

The influence of color vision deficiency on vessel visibility during colorectal endoscopic submucosal dissection and the potential advantage of red dichromatic imaging to achieve color vision barrier-free.

Objectives: Although color information is important in gastrointestinal endoscopy, there are limited studies on how endoscopic images are viewed by people with color vision deficiency. We aimed to investigate the differences in the visibility of blood vessels during endoscopic submucosal dissection (ESD) among people with different color vision characteristics and to examine the effect of red dichromatic imaging (RDI) on blood vessel visibility. Methods: Seventy-seven pairs of endoscopic images of white light imaging (WLI) and RDI of the same site were obtained during colorectal ESD. The original images were set as type C (WLI-C and RDI-C), a common color vision. These images were computationally converted to simulate images perceived by people with color vision deficiency protanope (Type P) or deutanope (Type D) and denoted as WLI-P and RDI-P or WLI-D and RDI-D. Blood vessels and background submucosa that needed to be identified during ESD were selected in each image, and the color differences between these two objects were measured using the color difference (ΔE 00) to assess the visibility of blood vessels. Results: ΔE 00 between a blood vessel and the submucosa was greater under RDI (RDI-C/P/D: 24.05 ± 0.64/22.85 ± 0.66/22.61 ± 0.64) than under WLI (WLI-C/P/D: 22.26 ± 0.60/5.19 ± 0.30/8.62 ± 0.42), regardless of color vision characteristics. This improvement was more pronounced in Type P and Type D and approached Type C in RDI. Conclusions: Color vision characteristics affect the visibility of blood vessels during ESD, and RDI improves blood vessel visibility regardless of color vision characteristics.

Analysis of lens cloudiness during endoscopic submucosal dissection procedures: Effects of a novel lens cleaner.

Objectives: We aimed to identify independent factors for intraoperative endoscopic lens cloudiness during gastric and colorectal endoscopic submucosal dissections, investigate the effectiveness of Cleastay, an endoscope anti-fog solution, and examine factors associated with severe submucosal fat deposition. Methods: A total of 220 patients who underwent gastric or colorectal endoscopic submucosal dissections in two institutions between January 2022 and October 2023 were included. Significant factors related to cloudiness were determined using univariate and multivariate analyses. Patient background and tumor characteristics related to severe submucosal fat deposition were investigated, and the degree of intraoperative endoscopic lens cloudiness and outcomes were compared between the Cleash and Cleastay groups. Results: In the multivariate analysis, factors increasing lens cloudiness included long procedure time (odds ratio [OR], 17.51; 95% confidence interval [CI], 1.52-202.08), stomach (vs. colon; OR, 5.08; 95% CI, 1.99-12.96), and severe submucosal fat deposition (OR, 12.19; 95% CI, 5.02-29.60). Conversely, the use of Cleastay (vs. Cleash; OR, 0.066; 95% CI, 0.021-0.21) was identified as a factor reducing cloudiness. Location analysis revealed that severe submucosal fat deposition was more common in the upper stomach and right colon. Conclusions: It was suggested that Cleastay is more useful for endoscopic submucosal dissection of the upper stomach and right colon, where severe submucosal fat deposition is expected.

Safety and efficacy of low-power pure-cut hot snare polypectomy for small nonpedunculated colorectal polyps compared with conventional resection methods: A propensity score matching analysis.

Objectives: Cold snare polypectomy (CSP) is widely performed for small colorectal polyps. However, small colorectal polyps sometimes include high-grade adenomas or carcinomas that require endoscopic resection with electrocautery. This study aimed to evaluate the efficacy and safety of a novel resection technique, hot snare polypectomy with low-power pure-cut current (LPPC-HSP) for small colorectal polyps, compared with CSP and conventional endoscopic mucosal resection (EMR). Methods: Records of patients who underwent CSP, EMR, or LPPC-HSP for nonpedunculated colorectal polyps less than 10 mm between April 2021 and March 2022 were retrospectively evaluated. We analyzed and compared the treatment outcomes of CSP and EMR with those of LPPC-HSP using propensity score matching. Results: After propensity score matching of 396 pairs, an analysis of CSP and LPPC-HSP indicated that LPPC-HSP had a significantly higher R0 resection rate (84% vs. 68%; p < 0.01). Delayed bleeding was observed in only two cases treated with CSP before matching. Perforation was not observed with either treatment. After propensity score matching of 176 pairs, an analysis of EMR and LPPC-HSP indicated that their en bloc and R0 resection rates were not significantly different (99.4% vs. 100%, p = 1.00; 79% vs. 81%, p = 0.79). Delayed bleeding and perforation were not observed with either treatment. Conclusions: The safety of LPPC-HSP was comparable to that of CSP. The treatment outcomes of LPPC-HSP were comparable to those of conventional EMR for small polyps. These results suggest that this technique is a safe and effective treatment for nonpedunculated polyps less than 10 mm.

Genes da instabilidade de microssatélites no câncer colorretal: papel na inflamação e estresse oxidativo / Microsatellite instability genes in colorectal cancer: role in inflammation and oxidative stress

A instabilidade de microssatélites é um fenômeno genético caracterizado pela alteração na repetição de sequências de nucleotídeos conhecidas como microssatélites. Esta instabilidade pode ocorrer devido a defeitos nos genes reparadores de DNA, como os genes MLH1, MSH2, MSH6 e PMS2. A inflamação crônica tem sido associada ao desenvolvimento do câncer colorretal. Os genes da instabilidade de microssatélites estão envolvidos na regulação da resposta inflamatória, podendo influenciar a progressão tumoral. Estudos demonstraram que a presença de instabilidade de microssatélites em tumores colorretais está relacionada a uma maior infiltração de células imunes, como linfócitos T, macrófagos e neutrófilos, que podem modular a resposta inflamatória no microambiente tumoral. O estresse oxidativo é caracterizado pelo desequilíbrio entre a produção de espécies reativas de oxigênio e a capacidade antioxidante do organismo e desempenha um papel importante na carcinogênese. Os genes da instabilidade de microssatélites podem influenciar a resposta ao estresse oxidativo, afetando a capacidade das células tumorais de lidar com o dano oxidativo e promovendo a sobrevivência celular. O objetivo deste trabalho consiste na compreensão dos genes envolvidos na instabilidade de microssatélites no câncer colorretal e como eles contribuem para o desenvolvimento da doença, relacionando com processos inflamatórios e estresse oxidativo nas células tumorais. Justifica-se pela necessidade de compreensão das interconexões entre a instabilidade de microssatélites, inflamação e o estresse oxidativo em pacientes com câncer colorretal.

Microsatellite instability is a genetic phenomenon characterized by changes in the repetition of nucleotide sequences known as microsatellites. This instability may occur due to defects in DNA repair genes, such as the MLH1, MSH2, MSH6 and PMS2 genes. Chronic inflammation has been linked to the development of colorectal cancer. Microsatellite instability genes are involved in regulating the inflammatory response and may influence tumor progression. Studies have shown that the presence of microsatellite instability in colorectal tumors is related to a greater infiltration of immune cells, such as T lymphocytes, macrophages and neutrophils, which can modulate the inflammatory response in the tumor microenvironment. Oxidative stress is characterized by the imbalance between the production of reactive oxygen species and the body's antioxidant capacity and plays an important role in carcinogenesis. Microsatellite instability genes can influence the response to oxidative stress, affecting the ability of tumor cells to deal with oxidative damage and promoting cell survival. The objective of this work is to understand the genes involved in microsatellite instability in colorectal cancer and how they contribute to the development of the disease, relating it to inflammatory processes and oxidative stress in tumor cells. It is justified by the need to understand the interconnections between microsatellite instability, inflammation and oxidative stress in patients with colorectal cancer.

Mental health in people living with and beyond colorectal cancer: A patient-oriented constructivist grounded theory.

BACKGROUND: With the burden of colorectal cancer in Canada, there is a need to address the psycho-oncologic challenges, including mental health. This study aims to explore the lived mental health experiences in patients with CRC across the phases of the CRC care continuum. METHODS: We employed a patient-oriented constructivist grounded theory design and recruited English speaking participants ≥18 years, diagnosed with CRC within the last 10 years, residing in Canada. We collected data through semi-structured individual interviews using a guide co-constructed with patient research partners. Data collection and analysis were iterative, employed theoretical sampling, and culminated in a theoretical model. RESULTS: Twenty-eight participants diagnosed with CRC (18 females, 10 males), aged 18-63 years at time of diagnosis were interviewed, with representation across all CRC stages. There were 10 participants (36%) in treatment, 12 participants (43%) in follow-up, and 6 participants (21%) in the beyond phase. We constructed a patient-oriented theory illustrating the dynamic nature between one's self-identity and their mental health experiences across the CRC care continuum. Mental health experiences encompass emotional and cognitive-behavioral responses, expressed differently across phases. Mental health care experiences are also shaped by barriers, facilitators, and individual contextual factors, all of which influence their access to care. CONCLUSION: Our theory provides insight into the mental health experiences of patients with CRC across phases of the CRC care continuum. Understanding patients' emotional and cognitive-behavioral responses and care experiences can help identify opportunities to integrate mental health into CRC care.

The Association Between Surgical Site Infection and Prognosis of T4 Colorectal Cancer.

OBJECTIVES: Patients with T4 colorectal cancer have poor prognosis, wherein no prognostic factors have been established. Surgical site infection (SSI) has been reported to be one of the risk factors for colorectal cancer recurrence. In this study, we evaluated the relationship between SSI occurrence and prognosis of T4 colorectal cancer and the prognostic impact of the site of SSI occurrence. METHODS: We examined 100 patients with T4 colorectal cancer who underwent radical surgery between April 2002 and December 2017, in a retrospective case-control study, excluding stage IV cases, and classified them into two groups: without SSI (non-SSI) and with SSI (SSI). The five-year relapse-free survival (RFS) and overall survival (OS) were calculated and compared between the two groups. The relationship between prognosis and the SSI site was also assessed according to the SSI site in the incisional/deep and organ/space SSI groups.  Results: The without SSI and with SSI groups included 73 and 27 patients, respectively. The five-year RFS was 55.1% and 22.2% in the without SSI and with SSI groups, respectively (hazard ratio (HR), 2.224; 95% confidence interval (CI), 1.269-3.898; P=0.005). The five-year OS was 67.0% and 38.4% in the without SSI and with SSI groups, respectively (HR, 2.366; 95% CI, 1.223-4.575; P=0.010). The patients in the with SSI group had a significantly poorer prognosis compared with the without SSI group. By SSI site, the prognosis was significantly worse in patients with SSI in the incisional/deep SSI group. CONCLUSIONS: In T4 colorectal cancer, SSI occurrence was a high-risk factor for recurrence and may be a prognostic factor. This result suggested that patients with SSI occurrence may require close postoperative follow-up and appropriate adjuvant chemotherapy.

Molecular insights into kaempferol derivatives as potential inhibitors for CDK2 in colon cancer: pharmacophore modeling, docking, and dynamic analysis.

Cyclin-dependent kinase 2 (CDK2) has been recognized as one of the crucial factors in cell cycle regulation and has been proposed as a potential target for cancer therapies, particularly for colorectal cancer (CRC). Due to the increased incidence rate of CRC and challenges associated with existing treatment options, there is a need for efficient and selective anti-cancer compounds. The current work aims to explore the ability of novel kaempferol derivatives as CDK2 inhibitors by performing conceptual pharmacophore modeling, molecular docking, and molecular dynamic analysis. Kaempferol and its derivatives were obtained from PubChem, and the optimized 3D structures of the compounds were generated using Maestro Ligprep. Subsequently, a pharmacophore model was developed to identify compounds with high fitness values, resulting in the selection of several kaempferol derivatives for further study. We evaluated the ADMET properties of these compounds to assess their therapeutic potential. Molecular docking was conducted using Maestro and BIOVIA Discovery Studio version 4.0 to predict the binding affinities of the compounds to CDK2. The top candidates were subjected to MM-GBSA analysis to predict their binding free energies. Molecular dynamics simulations using GROMACS were performed to assess the thermodynamic stability of the ligand-protein complexes. The results revealed several kaempferol derivatives with high predicted binding affinities to CDK2 and favorable ADMET properties. Specifically, compounds 5281642, 5318980, and 14427423 demonstrated binding free energies of -30.26, -38.66, and -34.2 kcal/mol, respectively. Molecular dynamics simulations indicated that these ligand-protein complexes remained stable throughout the simulation period, with RMSD values remaining below 2 Å. In conclusion, the identified kaempferol derivatives show potential as CDK2 inhibitors based on computational predictions and demonstrate stability in molecular dynamics simulations, suggesting their future application in CRC treatment by targeting CDK2. These computational findings encourage further experimental validation and development of kaempferol derivatives as anti-cancer agents.

Efficacy and safety of hepatic arterial infusion chemotherapy combined with fruquintinib and tislelizumab for patients with microsatellite stable colorectal cancer liver metastasis following failure of multiple-line therapy.

Background and aim: The prognosis of microsatellite stable (MSS)-colorectal cancer liver metastasis (CRCLM) following failure of multi-line therapy remains dismal. The aim of this study is to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) plus fruquintinib and tislelizumab (HAIC-F-T treatment) for MSS-CRCLM which failed from multiple-line therapy. Methods: From February 2021 to June 2023, 45 patients with MSS-CRCLM after failure of multiple-line therapy who received HAIC combined with fruquintinib and tislelizumab (HAIC-F-T triple treatment) were enrolled. The combination therapy included HAIC regimens with oxaliplatin and 5-fluorouracil or irinotecan, oxaliplatin, and 5-fluorouracil on days 1-2, intravenous tislelizumab (200 mg) before HAIC on day 1, and oral fruquintinb (3 mg/d) on day 3-21, every 4 weeks. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Results: The follow-up ended on June 22, 2024, with a median follow-up time of 17.5 months. The objective response rate was 42.2%, and the disease control rate was 82.2%. The median OS was 15.3 months (95% confidence interval [CI]:12.634-17.966), and the median PFS was 7.5 months (95% CI:5.318-9.682). The independent risk factors related to worse OS were previous PD-1 immunotherapy (P = 0.021) and the number of HAIC-F-T triple treatment cycles of ≤ 2 (P = 0.007). The incidence of grade 3 or higher adverse events (AEs) was 20%, with the most frequent grade 3 or higher AEs being abdominal pain (3/45, 6.7%). Conclusion: HAIC combined with fruquintinib and tislelizumab may be an alternative salvage treatment for patients with MSS-CRCLM following failure of multiple-line therapy.

Supportive care needs, quality of life and social support among elderly colorectal cancer patients undergoing chemotherapy: a longitudinal study.

Objective: The purpose of this study is to examine the changes in supportive care needs, quality of life and social support during different chemotherapy cycles among elderly colorectal cancer patients. Methods: This prospective longitudinal study recruited 160 elderly colorectal cancer patients using convenience sampling at a hospital in Guangxi between August 2023 and April 2024. To assess supportive care needs, quality of life, and social support, we used a short form of the Supportive Care Needs Survey (SCNS-SF34), a Functional Assessment of Cancer Therapy-colorectal (FACT-C), and a perceived social support scale (PSSS) prior to chemotherapy, as well as after the first, third, and sixth cycles. Repeated measures analysis of variance was used to validate the changes over time in supportive care needs, quality of life, and social support. Results: 155 participants completed all questionnaire sessions across the six cycles. From pre-chemotherapy until after the sixth cycle of chemotherapy, the extent of physical and daily living requirements among all respondents fluctuated between 47.23% and 88.26%, psychological needs ranged from 60.84% to 97.67%, patient care and support needs ranged from 83.75% to 99.35%, healthcare system and information needs varied from 85.98% to 99.00%, while the level of sexual needs decreased from 1.51% to 0.65%. The mean SCNS-SF34 scores for these participants ranged between 103.81 ± 2.28 and 144.10 ± 1.08. Significant increases over time were seen for all domains of SCNS-SF34 (F=126.99, 347.41, 65.00, 72.34, 160.15, p<0.001), keeping a clear upward trend, except for sexual needs(F=0.712, p=0.546). The mean FACT-T scores dropped from 68.80 ± 1.00 to 51.24 ± 1.40, while the mean PSSS scores dropped from 55.77 ± 0.83 to 43.28 ± 1.05. The scores of FACT-T and PSSS showed statistically significant differences (F=231.21, 112.28, p<0.001), maintaining clear downward trends. Conclusion: During chemotherapy, elderly colorectal cancer patients continue to require high levels of supportive care, while their quality of life and social support gradually decline. This study offers healthcare practitioners a foundational understanding to identify and address the supportive care needs of elderly colorectal cancer patients across various chemotherapy phases, which facilitates the development of tailored strategies aimed at enhancing patients' quality of life.

Estimated incidence of disruptions to event-free survival from non-metastatic cancers in New South Wales, Australia - a population-wide epidemiological study of linked cancer registry and treatment data.

Introduction: Population cancer registries record primary cancer incidence, mortality and survival for whole populations, but not more timely outcomes such as cancer recurrence, secondary cancers or other complications that disrupt event-free survival. Nonetheless, indirect evidence may be inferred from treatment data to provide indicators of recurrence and like events, which can facilitate earlier assessment of care outcomes. The present study aims to infer such evidence by applying algorithms to linked cancer registry and treatment data obtained from hospitals and universal health insurance claims applicable to the New South Wales (NSW) population of Australia. Materials and methods: Primary invasive cancers from the NSW Cancer Registry (NSWCR), diagnosed in 2001-2018 with localized or regionalized summary stage, were linked to treatment data for five common Australian cancers: breast, colon/rectum, lung, prostate, and skin (melanomas). Clinicians specializing in each cancer type provided guidance on expected treatment pathways and departures to indicate remission and subsequent recurrence or other disruptive events. A sample survey of patients and clinicians served to test initial population-wide results. Following consequent refinement of the algorithms, estimates of recurrence and like events were generated. Their plausibility was assessed by their correspondence with expected outcomes by tumor type and summary stage at diagnosis and by their associations with cancer survival. Results: Kaplan-Meier product limit estimates indicated that 5-year cumulative probabilities of recurrence and other disruptive events were lower, and median times to these events longer, for those staged as localized rather than regionalized. For localized and regionalized cancers respectively, these were: breast - 7% (866 days) and 34% (570 days); colon/rectum - 15% (732 days) and 25% (641 days); lung - 46% (552 days) and 66% (404 days); melanoma - 11% (893 days) and 38% (611 days); and prostate - 14% (742 days) and 39% (478 days). Cases with markers for these events had poorer longer-term survival. Conclusions: These population-wide estimates of recurrence and like events are approximations only. Absent more direct measures, they nonetheless may inform service planning by indicating population or treatment sub-groups at increased risk of recurrence and like events sooner than waiting for deaths to occur.

Colorectal cancer-specific microbiome in peripheral circulation and cancer tissues.

Introduction: Accumulating evidence has supported that gut microbiota and metabolite profiles play indispensable roles in the pathogenesis of colorectal cancer (CRC), which ranks as the third most common cancer and the second leading cause of cancer-related deaths worldwide. However, alterations in tumoral or circulating microbiomes in CRC remain incompletely understood. It has been well-documented that tissue or serum microbiomes with low microbial biomass could be screened by use of 2bRAD sequencing for microbiome (2bRAD-M) at the species resolution. Methods: In order to validate the microbial biomarkers distinguishing CRC and the variations in microorganisms present in serum and tumors, we performed 2bRAD-M to characterize the microbiomes in serum and cancer tissues of CRC patients with and without lymph node or liver metastasis. Results: The composition of dominated microbiota in serum was different from that of tissue samples, while the microbial community composition of tumors was similar to that of the tumor-adjacent tissues. The analysis of α-diversity and ß-diversity has revealed notable variations in serum microbiota diversities in CRC patients, particularly those with liver metastasis. Multiple CRC-specific microbial species, such as Moraxella A cinereus, Flavobacterium sp001800905, and Acinetobacter albensis, were identified in serum. Complicated functions and KEGG pathways were also confirmed in CRC according to the metastasis status. Discussion: This study has found significant alterations in the microbial compositions and diversities in CRC and CRC-specific microbial species in both circulation and cancer tissues, which may serve as promising biomarkers for the screening, diagnosis and prognosis prediction of CRC. In particular, CRC-specific bacterial taxa are promising markers, holding transformative potentials in establishing personalized screening and risk stratification, refining much earlier non-invasive diagnostic approaches, and enhancing diagnostic sensitivity.

Endoplasmic reticulum-targeted delivery of celastrol and PD-L1 siRNA for reinforcing immunogenic cell death and potentiating cancer immunotherapy.

The prospect of employing chemoimmunotherapy targeted towards the endoplasmic reticulum (ER) presents an opportunity to amplify the synergistic effects of chemotherapy and immunotherapy. In this study, we initially validated celastrol (CEL) as an inducer of immunogenic cell death (ICD) by promoting ER stress and autophagy in colorectal cancer (CRC) cells. Subsequently, an ER-targeted strategy was posited, involving the codelivery of CEL with PD-L1 small interfering RNAs (siRNA) using KDEL peptide-modified exosomes derived from milk (KME), to enhance chemoimmunotherapy outcomes. Our findings demonstrate the efficient transportation of KME to the ER via the Golgi-to-ER pathway. Compared to their non-targeting counterparts, KME exhibited a significant augmentation of the CEL-induced ICD effect. Additionally, it facilitated the release of danger signaling molecules (DAMPs), thereby stimulating the antigen-presenting function of dendritic cells and promoting the infiltration of T cells into the tumor. Concurrently, the ER-targeted delivery of PD-L1 siRNA resulted in the downregulation of both intracellular and membrane PD-L1 protein expression, consequently fostering the proliferation and activity of CD8+ T cells. Ultimately, the ER-targeted formulation exhibited enhanced anti-tumor efficacy and provoked anti-tumor immune responses against orthotopic colorectal tumors in vivo. Collectively, a robust ER-targeted delivery strategy provides an encouraging approach for achieving potent cancer chemoimmunotherapy.

Gut microbial subtypes and clinicopathological value for colorectal cancer.

BACKGROUND: Gut bacteria are related to colorectal cancer (CRC) and its clinicopathologic characteristics. OBJECTIVE: To develop gut bacterial subtypes and explore potential microbial targets for CRC. METHODS: Stool samples from 914 volunteers (376 CRCs, 363 advanced adenomas, and 175 normal controls) were included for 16S rRNA sequencing. Unsupervised learning was used to generate gut microbial subtypes. Gut bacterial community composition and clustering effects were plotted. Differences of gut bacterial abundance were analyzed. Then, the association of CRC-associated bacteria with subtypes and the association of gut bacteria with clinical information were assessed. The CatBoost models based on gut differential bacteria were constructed to identify the diseases including CRC and advanced adenoma (AA). RESULTS: Four gut microbial subtypes (A, B, C, D) were finally obtained via unsupervised learning. The characteristic bacteria of each subtype were Escherichia-Shigella in subtype A, Streptococcus in subtype B, Blautia in subtype C, and Bacteroides in subtype D. Clinical information (e.g., free fatty acids and total cholesterol) and CRC pathological information (e.g., tumor depth) varied among gut microbial subtypes. Bacilli, Lactobacillales, etc., were positively correlated with subtype B. Positive correlation of Blautia, Lachnospiraceae, etc., with subtype C and negative correlation of Coriobacteriia, Coriobacteriales, etc., with subtype D were found. Finally, the predictive ability of CatBoost models for CRC identification was improved based on gut microbial subtypes. CONCLUSION: Gut microbial subtypes provide characteristic gut bacteria and are expected to contribute to the diagnosis of CRC.

The effects of aromatherapy massage given to patients after colorectal cancer surgery on symptom management: A randomized controlled study.

BACKGROUND AND PURPOSE: It was aimed to investigate the effects of massage with or without aromatherapy given to patients after colorectal cancer surgery on symptom management in the first three postoperative days. MATERIALS AND METHODS: This study was carried out with a pretest-posttest randomized controlled design. The study included the aromatherapy massage group (AG; n = 30), the classical massage group (MG; n = 30), and one control group (CG; n = 30). A blend of sweet almond oil, lavender, chamomile, and ginger oil was used in AG. Massage was applied to the foot area, and 20 min of classical massage was performed. Before the pretest, the participants were blinded by not informing them about their group allocations. The analyses were carried out using parametric methods. RESULTS: Postoperative pain varied significantly over time in all three groups (AG: p = 0.007; η2 = 0.150/MG: p = 0.008; η2 = 0.559/CG: p = 0.017; η2 = 0.132). Anxiety was found to differ between CG and AG and between CG and MG (p < 0.05). In all three groups, nausea-vomiting scores significantly decreased over time (AG: p = 0.002; η2 = 0.211/MG: p = 0.004; η2 = 0.164/CG: p = 0.021; η2 = 0.125). Sleep quality was significantly higher in the massage groups than in the control group only on the second postoperative day (p = 0.011). CONCLUSION: Aromatherapy massage had no significant effect on pain, fatigue, nausea, or vomiting compared to MG and CG, and sleep quality was higher in the massage groups compared to CG only on the second postoperative day. On the first three postoperative days, the post-intervention anxiety levels of AG and MG were lower than those of CG. CLINICALTRIALS: GOV.ID: NCT04810299.

An observational cohort of patients with colorectal peritoneal metastases or pseudomyxoma peritonei treated with CRS-HIPEC: Development and first results of the Dutch CRS-HIPEC quality registry.

INTRODUCTION: To improve care for patients with colorectal peritoneal metastases (CRC-PM) or pseudomyxoma peritonei (PMP), the Dutch CRS-HIPEC quality registry was initiated in 2019. The aims are to describe the development and content of this registry and to give insight into the data collected during the first years. MATERIALS AND METHODS: The registry is an observational cohort in the Netherlands. All patients with CRC-PM or PMP who intend to undergo cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) from 6 hospitals are included. Clinical data and outcomes (including hospital variation) were analyzed. RESULTS: In 2019-2022, 889 patients were included in the CRS-HIPEC quality registry: 749 (84 %) with CRC-PM and 140 (16 %) with PMP. Peritoneal metastases were diagnosed synchronously in 51 % of CRC-PM patients and in 94 % of PMP patients. In patients undergoing complete CRS, the median peritoneal cancer index was 8 (IQR 4-13) for CRC-PM and 15 (IQR 6-26) for PMP. Complete cytoreduction was achieved in 639 CRC-PM patients (97 %) and 108 PMP patients (82 %). HIPEC was mainly performed with mitomycin C (CRC-PM: 94 %, PMP: 92 %). Major postoperative complications (Clavien-Dindo grade ≥3) occurred in 148 CRC-PM patients (22 %) and 30 PMP patients (23 %) with 90-day mortality rates of 2 %. In CRC-PM, differences between hospitals were observed regarding proportions of diagnostic laparoscopies/laparotomies, (neo)adjuvant treatment, ostomy formations and re-admissions. CONCLUSION: The CRS-HIPEC quality registry provides insight into the outcomes of CRS-HIPEC and enables clinical auditing and observational cohort studies aiming to improve treatment outcomes for patients with CRC-PM and PMP.

Epidemiology of gastrointestinal cancers: a systematic analysis from the Global Burden of Disease Study 2021.

BACKGROUND: Gastrointestinal cancers comprise nearly one-third of global mortality from cancer, yet the comprehensive global burden of these cancers remains uninvestigated. OBJECTIVE: We aimed to assess the global, regional and national burden of gastrointestinal cancers. DESIGNS: Data on oesophagus, gastric, colorectal, liver, pancreas and biliary tract cancers were extracted from the Global Burden of Disease 2021 database. Age-standardised incidence rate (ASIR) and age-standardised death rate (ASDR) were calculated by sex, region and Sociodemographic Index (SDI). RESULTS: In 2021, there were 5.26 million incidences and 3.70 million deaths from gastrointestinal cancer. The greatest burden is from colorectal, followed by gastric, oesophageal, pancreatic, liver and biliary tract cancer. We noted geographical and socioeconomic differences in ASIR and ASDR across all types of cancers. From 2000 to 2021, ASIR increased for colorectal cancer (annual percent change (APC): 0.10%, 95% CI 0.05% to 0.14%), pancreatic cancer (APC: 0.27%, 95% CI 0.14% to 0.41%), and liver cancer from metabolic dysfunction-associated steatotic liver disease (APC: 0.62%, 95% CI 0.58% to 0.67%) and alcohol-related liver disease (APC: 0.26%, 95% CI 0.22% to 0.30%). ASDR increased for pancreatic cancer (APC: 0.18%, 95% CI 0.02% to 0.34%). Higher SDI countries had higher incidence rates for most types of gastrointestinal cancer. CONCLUSIONS: Although the ASIR of oesophageal, gastric and biliary tract cancer has decreased, the ASIR still increased in colorectal, pancreatic and liver cancer from steatotic liver disease. Public policies are important for controlling gastrointestinal cancers-most importantly, reducing alcohol consumption, hepatitis B immunisation and tackling the burden of metabolic diseases.

High-risk rural surgical patients and poor access to elective colorectal cancer surgery: insight for multilevel intervention for rural America.

BACKGROUND: Colorectal cancer (CRC) is a leading cause of death in rural America. Rural populations are large and heterogeneous, yet patient-related drivers of inequities in CRC access are understudied. This study aimed to identify vulnerable rural populations at lower odds of undergoing elective CRC surgery. METHODS: Evaluation of the Policy Map and United States Census Bureau identified factors associated with poor surgical access in the most populous states (by total rural population). To assess whether these identified factors were associated with reduced access to elective CRC surgery, the 2007 to 2020 National Inpatient Sample was used to evaluate 69,212 hospitalizations of rural patients undergoing CRC surgery. Rural was defined as counties with a population of <250,000. Multivariable logistic regression models assessed predictors of elective CRC surgery. Patient- and hospital-level factor interactions were specified a priori. RESULTS: More than 72% of hospitalizations of rural patients were elective. Multivariate regression analysis demonstrated that older age, multimorbidity, Black race, Latino-Hispanic ethnicity, Medicaid insurance, and rural hospitals predicted lower odds of elective CRC surgery. On interaction analyses, high-risk patients were less likely to undergo elective CRC surgery in urban facilities relative to rural. CONCLUSION: In this large study of rural dwellers, ethnoracial minorities, elders, and Medicaid beneficiaries had profoundly less access to elective CRC surgery, especially when care was received in urban settings. Future studies should focus on exploring actionable social drivers of health in these rural populations. Findings underscore the need for multilevel interventions to enhance rural access to equitable and quality surgical cancer care.