Treatment Differences for Splenic Flexure Cancers in Saudi Arabia: A Cross-Sectional Study.

Backgrounds Colorectal surgeons worldwide have differing opinions on the best way to handle rare cases of splenic flexure colon cancers (SFCs). Although the majority of reviews indicate no significant variation in oncological outcomes among the three different procedure types used to treat SFCs, surgeons still exhibit diversity in their practices. This study determined the treatment preferences of colorectal surgeons in Saudi Arabia. Methods A descriptive cross-sectional study evaluated the management of colorectal surgeons in handling SFC cases. We utilized a validated questionnaire developed by Manceau et al., consisting of 14 questions. Emails and phone numbers of members of the Saudi Society of Colorectal Surgery (SSCRS) were gathered. Google Forms surveys were administered from October 1-30, 2023. Results A response rate of 66% (58/88) was obtained among questioned colorectal surgeons. Their responses revealed that there was no consensus regarding the preferred procedure to treat SFCs. The most common treatment reported was segmental colectomy (SC) 21/58 (36.2%), followed by subtotal colectomy (STC) (19/58, 32.8%) and left hemicolectomy (LHC) (18/58, 31%). There was a strong consensus of 96% (56/58) of the respondents in favor of using stapler anastomosis rather than hand sewing. The frequency of performing SC, STC, and LHC in France was 70%, 13%, and 17%, respectively, compared to 36.2%, 32.8%, and 31% in Saudi Arabia, with a p-value of 0.001. The surgeons' preferred approaches to managing SFCs utilizing laparoscopic, open, or hand-aided in France versus Saudi Arabia were 63%, 31%, and 11%, respectively, compared to 84.5%, 8.6%, and 6.9%, with a p-value of 0.001. Conclusion A significant disparity exists regarding the treatment of SFCs between colorectal surgeons in France and Saudi Arabia. Furthermore, there is a lack of consensus among colorectal surgeons in Saudi Arabia regarding the surgical management of SFCs. Hence, it is imperative for the SCRSS to assemble a panel of experts to reach a consensus for the most appropriate and effective treatment of SFCs.

Tumour Budding Is a Useful Predictor to Identify High-Risk Stage II Colon Cancer Patients After Curative Surgery.

Aim. Although it is now accepted in the literature that tumour budding (TB) is a useful survival indicator in colon cancer (CC), there are still uncertainties about daily use. Here we methodologically examined the role of TB on survival in CC. Methods. In our study, we examined colon cancer patients who had surgery up to 15 years before presentation. TB was calculated separately using different comprehensive methodological methods. Results. We first investigated an optimal evaluation method. Relationship with prognostic factors was better (Venous invasion [p = .001], advanced pT [p = .003], perineural invasion [p = .040], MSS [p = .016], advanced size [p = .001], tumour obstruction [p = .005], margin involvement [p = .043], and nodal involvement [p = .028]) in Method-1. Similarly, with the same method, the success of the cut-off value, the correlation of TB data (r = .724), and the repeatability of the method (Κappa = .53-.75) were quite good (ROC = .816 [.707-.925]). Then, survival analysis was performed using the best three methods, including this method. In univariate analysis using Method-1, survival analyses were worse in high TB patients (RFS: 81%, p < .001; OS: 84%, p < .001). Multivariate analyses using the same method confirmed that high TB for RFS and OS was an independent poor prognostic parameter for survival (p = .002, Hazard ratio [HR]: 1.42 [1.13-1.80]) and OS (p = .014, HR: 1.38 [1.07-1.79]). Conclusions. With our study, we showed that tumour budding calculated by the standard method is a very valuable prognostic parameter in stage II CC and can contribute to the detection of patients with poor prognosis in stage II CC.

Anticancer Activity of Iso-Mukaadial Acetate on Pancreatic and Colon Cancer Cells.

Background: Pancreatic cancer and colon cancer pose significant challenges in treatment, with poor prognoses. Natural products have long been explored for their potential as anticancer agents. Iso-mukaadial acetate has shown promise in inducing apoptosis in breast and ovarian cancer cells. The objective of this study was to investigate the effect of Iso-mukaadial acetate on pancreatic (MIA-PACA2) and colon (HT29) cancer cell lines. Methods: Pancreatic (MIA-PACA2) cancer cells, colon (HT29) cancer cells, normal embryonic kidney cells (HEK 293), and normal lung cells (MRC5) were cultured and treated with Iso-mukaadial acetate (IMA) for 24 hours. The viability assays were conducted using Alamarblue reagent and a real-time cell viability monitoring system, xCELLigence. The IC50 values were determined, followed by assessments of ATP production, caspase 3/7 activation, mitochondrial function, morphological changes using a light microscope, and gene expression changes via RT-PCR. Results: This study indicates that Iso-mukaadial acetate exhibited concentration-dependent cytotoxic effects, slowing cellular proliferation in both cancer cell lines. Activation of the mitochondrial apoptotic pathway and caspase 3/7 suggests induction of apoptosis. Reduced ATP production and altered gene expression further support its anticancer properties. Morphological changes after treatment with Iso-mukaadial acetate showed apoptotic characteristics which may suggest that apoptosis was induced. Conclusions: According to the results obtained, Iso-mukaadial acetate shows potential as an anticancer agent, evidenced by its effects on cellular viability, mitochondrial function, ATP production, caspase activation, and gene expression in pancreatic and colon cancer cells. These findings highlight its promise for further investigation and potential in the development of therapeutic agents.

Does Colorectal Stenting as a Bridge to Surgery for Obstructive Colorectal Cancer Increase Perineural Invasion?

Objectives: To clarify whether self-expandable metallic stent (SEMS) placement for obstructive colorectal cancer (CRC) increases perineural invasion (PNI), thereby worsening the prognosis. Methods: In total, 1022 patients with pathological T3 or T4 colon or rectosigmoid cancer who underwent resection were retrospectively reviewed. The study patients were divided into a no obstruction group (n=693), obstruction without stent group (n=251), and obstruction with stent group (n=78), and factors demonstrating an independent association with PNI, the difference in PNI incidence and severity between groups, and the association between PNI and the duration from SEMS placement to surgery were investigated. Survival analysis was performed for each group. Results: On multivariate analysis, SEMS placement (hazard ratio [HR]: 2.08) was independently associated with PNI whereas SEMS placement was not. PNI occurred in 39%, 45%, and 68% of the no obstruction, obstruction without stent, and obstruction with stent group, respectively. In the obstruction with stent group, the proportion of PNI was not associated with the duration from SEMS placement to surgery. Extramural PNI, an advanced form of PNI, demonstrated no increase with increasing interval. The five-year OS was 86.3%, 76.7%, and 73.1% in no obstruction, obstruction without stent, and obstruction with stent group, respectively. On multivariate analysis, obstruction was an independent risk factor of decreased OS (HR: 1.57) whereas SEMS placement was not. Conclusions: The prognosis was comparable between patients with SEMS placement and those with an obstruction who did not undergo SEMS placement, thus demonstrating that SEMS is a viable, therapeutic option for BTS.

3D bioprinted CRC model brings to light the replication necessity of an oncolytic vaccinia virus encoding FCU1 gene to exert an efficient anti-tumoral activity.

The oncolytic virus represents a promising therapeutic strategy involving the targeted replication of viruses to eliminate cancer cells, while preserving healthy ones. Despite ongoing clinical trials, this approach encounters significant challenges. This study delves into the interaction between an oncolytic virus and extracellular matrix mimics (ECM mimics). A three-dimensional colorectal cancer model, enriched with ECM mimics through bioprinting, was subjected to infection by an oncolytic virus derived from the vaccinia virus (oVV). The investigation revealed prolonged expression and sustained oVV production. However, the absence of a significant antitumor effect suggested that the virus's progression toward non-infected tumoral clusters was hindered by the ECM mimics. Effective elimination of tumoral cells was achieved by introducing an oVV expressing FCU1 (an enzyme converting the prodrug 5-FC into the chemotherapeutic compound 5-FU) alongside 5-FC. Notably, this efficacy was absent when using a non-replicative vaccinia virus expressing FCU1. Our findings underscore then the crucial role of oVV proliferation in a complex ECM mimics. Its proliferation facilitates payload expression and generates a bystander effect to eradicate tumors. Additionally, this study emphasizes the utility of 3D bioprinting for assessing ECM mimics impact on oVV and demonstrates how enhancing oVV capabilities allows overcoming these barriers. This showcases the potential of 3D bioprinting technology in designing purpose-fit models for such investigations.

Metastatic Colon Cancer in an Individual Following Prolonged Daily Inulin Consumption.

Studies in rodents suggest that inulin supplements may be carcinogenic. We present a case implicating that this risk extends to humans. A healthy male from a family lacking history of cancer had his first cancer-screening colonoscopy at age 56. No intestinal polyps/abnormalities were detected. A second colonoscopy, performed 7 years later, revealed a tumor in the cecum, with evidence of metastasis to lymph nodes. The only known change in patient's lifestyle during that seven-year period was the addition of 4g of inulin powder as a daily supplement during the last 2 years. Such inulin consumption is a plausible contributor to his disease.

The impact of tumor size on the prognosis and chemotherapy efficacy in stage I/II colon cancer patients.

Background: The impact of tumor size on the survival and chemotherapy reponse of early-stage colon cancer remains unclear. Our study explored the effect of tumor size on overall survival (OS) and postoperative chemotherapy efficacy in patients with stage I/II colon cancer. Methods: Stage I/II colon cancer patients from the Surveillance, Epidemiology and End Results (SEER) database and a China center were extracted as two cohorts respectively. X-tile program was adopted to acquire optimal cutoff points of tumor size (16mm and 49mm). Harrell's concordance index (c-index) and time-dependent receiver operating characteristic curve (ROC) were used to indicate discrimination ability of prognostic factors. Results: Overall, 104,908 and 168 stage I/II postoperative colon cancer patients from SEER database and a China center were eligible, respectively. Kaplan-Meier analysis showed that large tumor size was associated with poor OS in two cohorts. The effect of tumor size on OS gradually decreased as the T stage increased both before PSM (c-index 0.535 for T1N0M0 and 0.506 for T4N0M0, p<0.05) and after PSM (c-index 0.543 for T1N0M0, p<0.05; c-index 0.543 for T4N0M0, p>0.05). Stratified analyses showed that chemotherapy improved the OS rate by 9.5% (chemotherapy vs. non-chemotherapy: 83.5% vs. 73.0%) or 12.8% (chemotherapy vs. non-chemotherapy: 85.7% vs. 72.9%) before and after PSM in T2N0M0 patients with tumor size >49 mm, but not in T1N0M0. The survival benefit provided by chemotherapy for T2N0M0 patients with large tumor was also validated in the Chinese cohort. Conclusions: Large tumor size was a risk factor for stage I/II colon cancer, especially for T1N0M0. Tumor size could serve as a complementary factor guiding postoperative chemotherapy for T2N0M0 patients.

Dysfunctional mucus structure in cystic fibrosis increases vulnerability to colibactin-mediated DNA adducts in the colon mucosa.

Colibactin is a recently characterized pro-carcinogenic genotoxin produced by pks+ Escherichia coli. We hypothesized that cystic fibrosis (CF)-associated dysfunctional mucus structure increases the vulnerability of host mucosa to colibactin-induced DNA damage. In this pilot study, we tested healthy-appearing mucosal biopsy samples obtained during screening and surveillance colonoscopies of adult CF and non-CF patients for the presence of pks+ E. coli, and we investigated the possibility of detecting a novel colibactin-specific DNA adduct that has not been yet been demonstrated in humans. While CF patients had a lower incidence of pks+ E. coli carriage (~8% vs 29%, p = 0.0015), colibactin-induced DNA adduct formation was detected, but only in CF patients and only in those who were not taking CFTR modulator medications. Moreover, the only patient found to have colon cancer during this study had CF, harbored pks+ E. coli, and had colibactin-induced DNA adducts in the mucosal samples. Larger studies with longitudinal follow-up should be done to extend these initial results and further support the development of colibactin-derived DNA adducts to stratify patients and their risk.

Oncologic safety of transverse colon cancer surgery without central vessel ligation of middle colic artery.

BACKGROUND: Surgical standardization for transverse colon cancers (TCC) has not been established, and the oncologic benefit of central vessel ligation (CVL) are still unclear. This study aimed to evaluate the oncologic safety of TCC surgery without CVL of the middle colic artery (MCA). METHODS: This is a single-center, retrospective, observational, comparative study. The clinical, surgical, and pathological characteristics of the patients who underwent radical surgery for non-metastatic TCC between January 2012 and December 2020 were investigated, and the characteristic and oncologic outcomes of No CVL and CVL groups were compared. RESULTS: The number of No CVL and CVL groups was 47 (44.3%) and 59 (55.7%), respectively. There was no statistically significant difference between the two groups in surgical complications, stage, mean number of retrieved lymph nodes (LN) (24.12 vs. 22.36 p = 0.464), mean number of metastatic LN (1.53 vs. 0.74, p = 0.163), mean proximal margin (19.2 cm vs. 16.7 cm, p = 0.139), mean distal margin (9.6 cm vs. 9.9 cm, p = 0.753), adjuvant chemotherapy, total recurrence rate (6.4 vs. 11.9%, p = 0.507), lymphatic recurrence rate (0.0% vs. 5.1%, p = 0.253), and local recurrence rate (2.1 vs. 1.7%, p = 0.984). Furthermore, there was no statistically significant difference of 5-year disease-free survival (DFS) and overall survival (OS) in stage II (DFS: 94.4 vs. 91.3%, p = 0.685, OS: 94.1 vs. 95.5%, p = 0.838) and stage III (DFS: 88.5 vs. 68.4%, p = 0.253, OS: 100.0% vs. 79.7, p = 0.328). CONCLUSION: TCC surgery without CVL of the MCA showed comparable surgical and oncologic outcomes compared to surgery with CVL. Therefore, preservation of a branch of the MCA may be considered a safe option, when combined with adequate lymph node dissection, if necessary. A large, prospective, and controlled study will be necessary to provide solid evidence of the oncologic safety of this procedure.

Clinical effect analysis of different regimens of capecitabine in the treatment of patients with advanced colon cancer.

To assess the efficacy and safety of capecitabine in treating advanced colon cancer. Patients with advanced colon cancer were randomized into three groups: control group (n = 50, daily dose 2,500 mg/m2), the medium-dose group (n = 50, daily dose 2,000 mg/m2), and the low-dose group (n = 50, daily dose 1,500 mg/m2) capecitabine for 4 cycles(12 weeks). Afterwards, the response rate, quality of life, and adverse reactions of the three groups were collected for comparison. Efficacy rates were 50%, 70%, and 72%, respectively, with the low-dose group showing the highest efficacy (χ2 = 6.424, p = 0.040); Quality of life comparison results indicated significant differences in physical function (F = 98.528, p < 0.001), role function (F = 123.418, p < 0.001), social function(F = 89.539, p < 0.001), emotional function (6 F = 77.295, p < 0.001), cognitive function (F = 83.529, p < 0.001), and overall quality of life (F = 99.528, p < 0.001) among the three groups, and the three groups returned consistent scores, with the low-dose group scoring highest. Incidence rates were 86.00%, 46.00%, 34.00%, with the control group having the highest rate (χ2 = 16.505, p < 0.001). Capecitabine at a dosage of 1,500 mg/m2 demonstrated a good therapeutic effect and improved the quality of life in patients with advanced colon cancer, with a lower incidence of adverse reactions. A prolonged treatment cycle with reduced dosage is suggested to further improve treatment outcomes and patient prognosis. Trial registration The study was registered on clicaltrials.gov 'NCT06246461' on 30/01/2024.

Hsa-miR-181a-2-3p inhibits the oncogenicity of colon cancer by directly targeting STING.

OBJECTIVE: Colon cancer is a common malignant tumor of the gastrointestinal system, which is characterized by high morbidity and mortality. The purpose of this study was to analyze the expression and biological role of miR-181a-2-3p in colon cancer and to investigate the molecular mechanism of its regulatory effect on colon cancer through stimulator of interferon genes (STING). METHODS: Real-time reverse transcription polymerase chain reaction (qRT-PCR) assay was used to detect the expression of miR-181a-2-3p in colon cancer cell lines and normal intestinal epithelial cells. After overexpression of miR-181a-2-3p in colon cancer cell lines SW480 and HT29, cells were examined by CCK8, Transwell, and flow cytometry assays for alterations in proliferation, migration, apoptosis, and cell cycle. Target genes of miR-181a-2-3p were predicted by bioinformatics and validated by dual luciferase assays. Rescue experiments were performed to explore the role of STING in the effect of miR-181a-2-3p. The effect of miR-181a-2-3p on colon cancer proliferation in vivo was validated by nude mouse tumorigenicity assay. RESULTS: miR-181a-2-3p was lowly expressed in both colon cancer tissues and cell lines. Overexpression of miR-181a-2-3p led to reduced proliferation and migration, increased apoptosis, and altered cell cycle in colon cancer cell lines SW480 and HT29. STING was a target gene of miR-181a-2-3p. Increased STING expression partially counteracted the effect of overexpression of miR-181a-2-3p on colon cancer cell lines. miR-181a-2-3p also suppressed colon cancer proliferation in vivo. CONCLUSION: miR-181a-2-3p inhibits the proliferation and oncogenicity of colon cancer, and its molecular mechanism could be inhibited by STING.

Biological and Clinical Characteristics of Proximal Colon Cancer: Far from Its Anatomical Subsite.

Colorectal cancer is a heterogeneous disease which can be divided into proximal colon cancer, distal colon cancer and rectal cancer according to the anatomical location of the tumor. Each anatomical location of colorectal cancer exhibits distinct characteristics in terms of incidence, clinical manifestations, molecular phenotypes, treatment, and prognosis. Notably, proximal colon cancer differs significantly from cancers of other anatomical subsites. An increasing number of studies have highlighted the presence of unique tumor biological characteristics in proximal colon cancer. Gaining a deeper understanding of these characteristics will facilitate accurate diagnosis and treatment approaches.

A cuproptosis-related lncRNAs signature predicts prognosis and reveals pivotal interactions between immune cells in colon cancer.

Copper-mediated cell death presents distinct pathways from established apoptosis processes, suggesting alternative therapeutic approaches for colon cancer. Our research aims to develop a predictive framework utilizing long-noncoding RNAs (lncRNAs) related to cuproptosis to predict colon cancer outcomes while examining immune interactions and intercellular signaling. We obtained colon cancer-related human mRNA expression profiles and clinical information from the Cancer Genome Atlas repository. To isolate lncRNAs involved in cuproptosis, we applied Cox proportional hazards modeling alongside the least absolute shrinkage and selection operator technique. We elucidated the underlying mechanisms by examining the tumor mutational burden, the extent of immune cell penetration, and intercellular communication dynamics. Based on the model, drugs were predicted and validated with cytological experiments. A 13 lncRNA-cuproptosis-associated risk model was constructed. Two colon cancer cell lines were used to validate the predicted representative mRNAs with high correlation coefficients with copper-induced cell death. Survival enhancement in the low-risk cohort was evidenced by the trends in Kaplan-Meier survival estimates. Analysis of immune cell infiltration suggested that survival was induced by the increased infiltration of naïve CD4+ T cells and a reduction of M2 macrophages within the low-risk faction. Decreased infiltration of naïve B cells, resting NK cells, and M0 macrophages was significantly associated with better overall survival. Combined single-cell analysis suggested that CCL5-ACKR1, CCL2-ACKR1, and CCL5-CCR1 pathways play key roles in mediating intercellular dialogues among immune constituents within the neoplastic microhabitat. We identified three drugs with a high sensitivity in the high-risk group. In summary, this discovery establishes the possibility of using 13 cuproptosis-associated lncRNAs as a risk model to assess the prognosis, unravel the immune mechanisms and cell communication, and improve treatment options, which may provide a new idea for treating colon cancer.

Evaluating Surgical Outcomes and Survival in Colon Cancer Patients Over 80 Years Old.

BACKGROUND AND AIMS: In the context of an increasing older population, knowing the surgical outcomes of older patients is of paramount importance to define a comprehensive strategy for colon cancer treatment in these patients. This study aimed to analyze the surgical outcomes and survival of patients over 80 years old undergoing surgery for colon cancer. MATERIALS AND METHODS: This is an observational retrospective longitudinal study of patients over 80 years old with colon cancer diagnosis who underwent surgery for this condition, between 2018 and 2021, in a Portuguese hospital. Demographic and clinical features were characterized. Kaplan-Meier method was used for survival analysis. RESULTS: Out of 90 patients in the study, 41.1% were female. The majority (56.7%) had an Eastern Cooperative Oncology Group (ECOG) performance status of 1 or 0, with a median Charlson Comorbidity Index of 7.0. Tumors were primarily located in the right colon (52.2%) and sigmoid colon (25.6%), with most patients having stage II (35.6%) or stage III (25.5%) disease. Elective surgeries accounted for 73% of procedures, and 80.0% had curative intent, with laparoscopic surgery performed in 66.7% of cases. Only 8.3% of those undergoing curative-intent procedures received adjuvant chemotherapy. Emergent admissions were associated with more advanced cancer stages, higher rates of palliative intent procedures (45.8% versus 10.6%, p < 0.001), and more open surgeries (75.0% versus 9.1%, p < 0.001) when compared to elective procedures. Postoperative mortality was higher in the emergent group (20.8% versus 10.6%), though there was no association between the type of admission and postoperative complications. Median overall survival for all patients was 36.7 (95% CI 28.1 to 45.3) months, with significant differences between curative-intent and palliative surgeries (median of 39.8 (95% CI 32.6 to 47.0) versus 10.6 (95% CI 0.67 to 20.5) months, p = 0.015). The elective group of patients had significantly better overall survival compared to the emergent group (median of 36.7 (95% CI 30.7 to 42.7) versus 11.9 (95% CI 6.0 to 17.8) months, p = 0.01). Among the patients who underwent curative-intent procedures, there were no significant differences in overall or disease-free survival between elective and emergent groups. CONCLUSIONS: Despite the increased complexity of managing older patients, particularly in emergent cases, these findings emphasize the importance of elective, curative-intent surgeries to optimize overall survival. Effective treatment strategies and perioperative management tailored to this age group are essential for improving surgical outcomes and extending survival in elderly colon cancer patients.

Neoadjuvant immunotherapy leads to complete pathologic response in locally advanced colon cancer.

Immunotherapy is considered first line in patients with dMMR metastatic colorectal cancer (CRC). Recent studies have also shown promising results with neoadjuvant immunotherapy in locally advanced CRC. We report a case in which neoadjuvant immunotherapy with pembrolizumab resulted in complete pathologic response at time of resection as well as saved the patient the morbidity associated with a hepatectomy. We also completed a scoping review of the literature which suggests promising tumor responses with treatment in dMMR CRC. Further randomized control trials to determine the magnitude of response and optimal regimen are needed.

Unveiling an anoikis-related risk model and the role of RAD9A in colon cancer.

OBJECTIVE: Colorectal cancer (CRC), specifically colon adenocarcinoma, is the third most prevalent and the second most lethal form of cancer. Anoikis is found to be specialized form of programmed cell death (PCD), which plays a pivotal role in tumor progression. This study aimed to investigate the role of the anoikis related genes (ARGs) in colon cancer. METHODS: Consensus unsupervised clustering, differential expression analysis, tumor mutational burden analysis, and analysis of immune cell infiltration were utilized in the study. For the analysis of RNA sequences and clinical data of COAD patients, data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were obtained. A prognostic scoring system for overall survival (OS) prediction was developed using Cox regression and LASSO regression analysis. Furthermore, loss-of-function assay was utilized to explore the role of RAD9A played in the progression of colon cancer. RESULTS: The prognostic value of a risk score composed of NTRK2, EPHA2, RAD9A, CDC25C, and SNAI1 genes was significant. Furthermore, these findings suggested potential mechanisms that may influence prognosis, supporting the development of individualized treatment plans and management of patient outcomes. Further experiments confirmed that RAD9A could promote proliferation and metastasis of colon cancer cells. These effects may be achieved by affecting the phosphorylation of AKT. CONCLUSION: Differences in survival time and the tumor immune microenvironment (TIME) were observed between two gene clusters associated with ARGs. In addition, a prognostic risk model was established and confirmed as an independent risk factor. Furthermore, our data indicated that RAD9A promoted tumorigenicityby activating AKT in colon cancer.

Defensins: Exploring Their Opposing Roles in Colorectal Cancer Progression.

Colorectal cancer (CRC) represents a significant global healthcare burden, with a particularly concerning rising incidence among younger adults. This trend may highlight potential links between diet, gut microbiome, and CRC risk. Novel therapeutic options have been increasingly based on the understanding of molecular mechanisms and pathways. The PI3K/AKT/mTOR pathway, a crucial cell growth regulator, offers a promising target for CRC therapy. mTOR, a key component within this pathway, controls cell growth, survival, and metabolism. Understanding the specific roles of defensins, particularly human ß-Defensin 1 (HBD-1), in CRC is crucial. HBD-1 exhibits potent antimicrobial activity and may influence CRC development. Deciphering defensin expression patterns in CRC holds the promise of improved understanding of tumorigenesis, which may pave the way for improved diagnostics and therapies. This article reviews recent advances in understanding regarding how HBD-1 influences CRC initiation and progression, highlighting the molecular mechanisms by which it impacts CRC. Further, we describe the interaction between defensins and mTOR pathway in CRC.

Colonic Adenosquamous Carcinoma: A Single-Center Review of Patient Clinicopathologic Characteristics, Genetics, and Clinical Outcomes.

(1) Background: Adenosquamous carcinoma (ASC) is a rare subtype of colon cancer. Its rarity makes characterization challenging, although colonic ASC is believed to present at more advanced stages and have worse outcomes versus adenocarcinoma. This study aims to characterize the clinicopathological characteristics and clinical outcomes of colonic ASC. (2) Methods: This is a single-center, retrospective review of patients diagnosed with colonic ASC from 2000 to 2020. Data extracted included patient demographics, staging at diagnosis, tumor clinicopathologic and genetic characteristics, and clinical outcomes. (3) Results: Among 61,126 patients with colorectal cancer, 13 (0.02%) had colonic ASC, with a mean age at diagnosis of 48.7 years. The cecum/ascending colon was the most common primary site (6/13, 46.2%), and all except one patient was diagnosed with Stage III or IV disease. Among the eight patients with mismatch repair genetics available, only one was mismatch repair deficient. Eleven patients (84.6%) underwent surgery, and 11 likewise received some form of chemotherapy. Recurrence occurred in 7 of 13 patients (53.8%), and the overall five-year survival rate was 38.5%. The median survival rate was 39.4 months overall (30.5 months for Stage III, 23.7 months for Stage IV). (4) Conclusions: Overall, colonic ASC is rare, and this cohort of colonic ASC patients demonstrated advanced stage at diagnosis, frequent recurrence, and poor overall survival. Additional research remains to compare these characteristics with those of comparably staged adenocarcinoma and to develop specific management recommendations.

Screening and Surveillance of Colorectal Cancer: A Review of the Literature.

Colorectal cancer (CRC) has the highest mortality rate among men and is the second highest among women under fifty, with incidence and mortality rates rising in younger populations. Studies indicate that up to one-third of patients diagnosed before fifty have a family history or genetic factors, highlighting the need for earlier screening. Contrariwise, diagnosis in healthy subjects through screening strategies enables early-stage detection of the tumor and better clinical outcomes. In recent years, mortality rates of CRC in Western countries have been on a steady decline, which is largely attributed to widespread screening programs and advancements in treatment modalities. Indeed, early detection through screening significantly improves prognosis, with stark differences in survival rates between localized and metastatic disease. This article aims to provide a comprehensive review of the existing literature, delving into the performance and efficacy of various CRC screening strategies. It navigates through available screening tools, evaluating their efficacy and cost-effectiveness. The discussion extends to delineating target populations for screening, emphasizing the importance of tailored approaches for individuals at heightened risk.