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Background: Colorectal cancer (CRC) remains a multifaceted disease with variations in aetiology, clinical presentation and prognostic factors. Objectives: This study explores the features and outcomes of sporadic (S-CRC), inflammatory bowel disease-associated CRC (IBD-CRC), early-onset CRC (EO-CRC) and late-onset CRC (LO-CRC). Design: This is a systematic review and meta-analysis performed following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) Statement, comparing S-CRC versus IBD-CRC and EO-CRC versus LO-CRC. Data sources and methods: The literature search was conducted on PubMed and Embase databases. The primary endpoint was the overall 5-year survival rate of CRC. Secondary aims included the features of CRC at diagnosis. Results: Fifty studies and 6,148,851 patients with CRC were included in the analysis. Comparing S-CRC and IBD-CRC, the overall survival was higher in S-CRC (61.88 (range 41.3–78.7) vs 55.54 (51.9–80.9) months). IBD-CRC showed a minor mean age of diagnosis (63.5 (45–78) vs 69.1 ((40–78) years), a minor risk of stage IV (odd ratio (OR) 1.091; 95%CI 1.031–1.155, p = 0.003, I2 60.24%), higher risk of mucinous tumour (OR 3.150 95%CI 2.797–3.548, p < 0.001, I2 96.56%), emergency diagnosis (OR 1.598, 95%CI 1.509–1.693, p < 0.001, I2 77.40%), and synchronous neoplasia (OR 1.942 95%CI 1.705–2.211, p < 0.001, I2 0.00%). Comparing EO-CRC and LO-CRC, OS was longer in EO-CRC (79.42 (54–96) vs 77.58 (32–92) months). EO-CRC had a higher risk of being diagnosed at stage IV (OR 1.471, 95%CI 1.456–1.486, p < 0.001, I2 97.12%), and of having mucinous tumours (OR 1.0142, 95%CI 1.015–1.070, p = 0.002, I2 60.48%) versus LO-CRC. Comparing IBD-CRC, EO-CRC and LO-CRC, IBD-CRC had the shortest OS (61.88 months), the highest rate of mucinous cancer (13%) and emergency diagnosis (24%), whereas metastatic disease at diagnosis was more common in EO-CRC (22.6%). Conclusion: IBD-CRC was associated with a younger mean age at diagnosis, higher risk of mucinous cancers, emergency presentation, and synchronous neoplasia compared to S-CRC. EO-CRC had a higher risk of being diagnosed at stage IV and of mucinous tumours versus LO-CRC. IBD-CRC seemed to have an overall shorter survival rate and a higher prevalence of mucinous cancers, suggesting different pathways of progression and more aggressive features. Trial registration: Prospero Registration ID1021182. Plain language summary Comparative analysis between sporadic vs inflammatory bowel disease-associated and early-onset vs late-onset colorectal cancer Colorectal cancer (CRC) remains a multifaceted disease with variations in etiology, clinical presentation, and prognostic factors. This study explores the characteristics of sporadic CRC (S-CRC), inflammatory bowel disease-associated CRC (IBD-CRC), early-onset CRC (EO-CRC), and late-onset CRC (LO-CRC). The review was conducted through a systematic review and meta-analysis comparing sporadic CRC with IBD-CRC and EO-CRC with LO-CRC. The literature search was conducted using PubMed and Embase databases. The primary endpoint was 5-year overall survival rate for CRC. Upon completion of the review, 50 studies and 6,148,851 CRC patients were included in the analysis. When comparing S-CRC and IBD-CRC, overall survival was higher in S-CRC, with IBD-CRC showing a lower mean age at diagnosis (63.5 [45-78] vs 69.1 [40-78] years), a lower risk of stage IV, higher risk of mucinous tumor, emergency diagnosis, and synchronous neoplasia. When comparing EO-CRC and LO-CRC, overall survival was higher in EO-CRC, although it had a higher risk of being diagnosed at stage IV and of presenting mucinous tumors compared to LO-CRC. When comparing IBD-CRC, EO-CRC, and LO-CRC, the first presented the shortest OS (61.88 months), the highest rates of mucinous cancer (13%) and emergency diagnosis (24%), while metastatic disease at diagnosis was more frequent in EO-CRC (22.6%). In conclusion, different analyzed groups of CRC presented differential features, suggesting different pathways of progression, as well as more aggressive features, particularly in IBD.

Colorectal cancer (CRC) is a leading cause of cancer-related deaths and obesity is a known risk factor for its development and poor prognosis. Adipose tissue (AT) actively contributes to CRC progression and cachexia. Here, we investigated molecular crosstalk between tumor cells and different visceral AT depots (normal, intra- and peri-tumoral), focusing on metabolic and (epi)genetic alterations. Using WGS analysis, we explored VAT role in CRC progression, demonstrating how its proximity to the tumor impacts metabolic and phenotypic changes. Intra-VAT (within 5 cm of lesion), closest to the tumor, underwent significant metabolic remodeling, characterized by upregulation of markers of the white-brown AT transition (UCP-1, TMEM26), lipid metabolism (PON3) and a reduction in adipocyte turnover (Pref-1, adiponectin). Peri-VAT (within 15 cm) and HVAT (over 15 cm) exhibited progressively fewer alterations, suggesting a gradient effect of tumor on surrounding AT. Intra-VAT displayed increased fibrosis (TGF-β, collagen) and cachexia-related markers (IL-8), and mutations in key oncogenes (KRAS, HLA, MET), highlighting a direct interaction between tumor cells and AT driving CRC progression. Mutations in genes such as KRAS, HLA, and PIK3CA were shared between CRC and its Intra-VAT, indicating potential biomarkers for tumor progression and immune evasion. miRNA analysis revealed upregulation of miR-21 and miR-92a in Intra-VAT, with circulating miR-92a correlating with increased body fat and decreased lean mass in CRC patients, suggesting their involvement in both local metabolic remodeling and systemic changes. Altered PON3 DNA methylation patterns were also observed, correlating with metabolic parameters. Our findings underscore AT’s critical role in the CRC microenvironment as an active player in CRC progression and cachexia. Metabolic and genetic alterations decreased in VAT with increasing distance from the tumor. Intra-VAT may serve as a critical therapeutic target and biomarker for CRC progression, impacting surgical and postoperative strategies. Future studies should focus on targeting tumor-adipose crosstalk to improve treatment outcomes, including experimental validation of the identified genetic alterations and investigation of their functional roles in tumor progression and immune evasion.

Purpose Although surgery is the most effective treatment for rectal prolapse, a risk of recurrence reported in literature is 6–27%. The aim of this meta-analysis is to compare the abdominal and perineal approach for surgical treatment of recurrent external rectal prolapse. Methods A systematic search of PubMed and Embase was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. A comprehensive literature search of PubMed and Embase was conducted from January 2000 to May 2024, for studies reporting surgery for recurrent external rectal prolapse. The primary outcome was the recurrence at the last available follow-up. Secondary endpoints included surgical complications and length of postoperative hospitalization. Results Nine studies, with a total of 531 patients, were included in the analysis. The overall recurrence rate among the studies was 26.3% at a mean follow-up time of 30.5 months. The proportional meta-analysis showed a recurrence rate of 27.9% (95% CI 22.54 to 33.85, I 2 75.1%, p  = 0.0012) after perineal surgery and of 15.6% (95% CI 11.43 to 20.64, I 2 63.7%, p  = 0.016) after abdominal surgery. Comparing the two approaches, the meta-analysis showed an OR of 0.66 (95% CI 0.41 to 1.17, I 2 66.5%, p  = 0.029). The OR for complications was 1.44 (95% CI 0.77 to 2.70, I 2 0.0%, p  = 0.945), while SMD for length of hospital stay was 0.49 (95% CI 0.20 to 0.79, I 2 - 67.9%, p = 0.077). Conclusions Our meta-analysis revealed that the recurrence rate for the perineal approach was almost double the recurrence rate for the abdominal approach. More randomized trials are needed to determine which is the best approach for patients with recurrent external rectal prolapse.

Purpose Crohn’s disease (CD) frequently requires surgery, with ileocolonic resection being the most common procedure. Postoperative endoscopic recurrence remains a major concern, and the role of anastomotic configuration is still debated. This systematic review and meta-analysis aimed to evaluate the impact of different anastomotic techniques on early endoscopic recurrence following ileocolonic resection for CD. Methods A systematic search of PubMed, Embase, and Web of Science was performed up to July 2025. Studies comparing stapled side-to-side anastomosis (SSA), handsewn end-to-end anastomosis (EEA), and Kono-S anastomosis (KSA) with postoperative endoscopic follow-up at 6–12 months were included. Study quality was assessed using the Newcastle–Ottawa Scale. Pooled analyses were conducted to compare recurrence rates across anastomotic types. Results Eleven studies were included (four comparing SSA vs. EEA; seven comparing KSA vs. SSA), for a total of 1505 patients. Most were retrospective, with three randomised controlled trials available. In pooled analysis, no significant difference was found between SSA and EEA (48.5% vs. 46.7%, test for overall effect Z = 0.41, p  = 0.6795). KSA showed a trend towards lower recurrences compared with SSA (31.8% vs. 39.8%, test for overall effect Z = −1.96, p  = 0.0495), although heterogeneity in study design, definitions, and postoperative management limits firm conclusions. Conclusions Current evidence does not support a difference in early endoscopic recurrence between SSA and EEA and a potential but weak overall association with lower recurrences for KSA compared to SSA. Large, high-quality prospective trials with standardised definitions, postoperative medical therapy, and follow-up protocols are warranted to clarify the true impact of anastomotic configuration on outcomes in CD.