Ondansetron for Low Anterior Resection Syndrome (LARS): A Double-Blind, Placebo-Controlled, Cross-Over, Randomized Study.

OBJECTIVE: The aim of the study was to examine the efficacity and safety of ondansetron, a serotonin receptor antagonist, to treat patients with low anterior resection syndrome (LARS). BACKGROUND: LARS after rectal resection is common and debilitating. Current management strategies include behavioral and dietary modifications, physiotherapy, antidiarrheal drugs, enemas, and neuromodulation, but the results are not always satisfactory. METHODS: This is a randomized, multicentric, double-blinded, placebo-controlled, and cross-over study. Patients with LARS (LARS score >20) no longer than 2 years after rectal resection were randomized to receive either 4 weeks of ondansetron followed by 4 weeks of placebo (O-P group) or 4 weeks of placebo followed by 4 weeks of ondansetron (P-O group). The primary endpoint was LARS severity measured using the LARS score; secondary endpoints were incontinence (Vaizey score) and irritable bowel syndrome quality of life (IBS-QoL questionnaire). Patients' scores and questionnaires were completed at baseline and after each 4-week treatment period. RESULTS: Of 46 randomized patients, 38 were included in the analysis. From baseline to the end of the first period, in the O-P group, the mean (SD) LARS score decreased by 25% [from 36.6 (5.6) to 27.3 (11.5)] and the proportion of patients with major LARS (score >30) went from 15/17 (88%) to 7/17 (41%), ( P =0.001). In the P-O group, the mean (SD) LARS score decreased by 12% [from 37 (4.8) to 32.6 (9.1)], and the proportion of major LARS went from 19/21 (90%) to 16/21 (76%). After crossover, LARS scores deteriorated again in the O-P group receiving placebo, but further improved in the P-O group receiving ondansetron. Mean Vaizey scores and IBS QoL scores followed a similar pattern. CONCLUSIONS: Ondansetron is a safe and simple treatment that appears to improve both symptoms and QoL in LARS patients.

Laparoscopic vs. ultrasound-guided transversus abdominis plane (TAP) block in colorectal surgery: a systematic review and meta-analysis of randomized trials.

BACKGROUND: The transversus abdominis plane block (TAPB) is effective for postoperative pain management in patients undergoing colorectal surgery. However, evidence regarding the optimal delivery method, either laparoscopic (L-TAPB) or ultrasound-guided (U-TAPB) is lacking. Our study aimed to compare the effectiveness of these delivery methods. METHODS: We carried out a literature search of PubMed, Cochrane Library, Web of Science, and Google Scholar databases to include randomized studies comparing patients receiving either L-TAPB or U-TAPB during minimally invasive colorectal surgery. The primary endpoint was opioid consumption in the first 24 h after surgery. Risk of bias was assessed with the RoB-2 tool. Effect size was estimated for each study with 95% confidence interval and overall effect measure was estimated with a random effect model. RESULTS: The literature search revealed 294 articles, of which four randomized trials were eligible. A total of 359 patients were included, 176 received a L-TAPB and 183 received a U-TAPB. We established the non-inferiority of L-TAPB, as the absolute difference of - 2.6 morphine-mg (95%CI - 8.3 to 3.0) was below the pooled non-inferiority threshold of 8.1 morphine-mg (low certainty level). No difference in opioid consumption was noted at 2, 6, 12, and 48 h (low to very low certainty level). Postoperative pain, nausea and vomiting were similar between groups at different timepoints (low to very low certainty level). No TAPB-related complications were recorded. Finally, the length of hospital stay was similar between groups. CONCLUSION: For postoperative multimodal analgesia both L-TAPB and U-TAPB may result in little to no difference in outcome in patients undergoing colorectal surgery. Registration Prospero CRD42023421141.

Laparoscopic versus ultrasound-guided transversus abdominis plane block in colorectal surgery: a non-inferiority, multicentric randomized double-blinded clinical trial.

AIM: The aim of this study was to assess if laparoscopic-assisted transversus abdominis plane (TAP) block (L-TAPB) is as efficient as ultrasound-guided TAP block (U-TAPB) in postoperative pain control. METHOD: In all, 112 patients scheduled for elective laparoscopic colon resection from February 2018 to December 2021 at two Swiss hospitals were included and randomized in a 1:1 ratio before surgery with either L-TAPB or U-TAPB. The primary end-point was the non-inferiority of the L-TAPB compared to U-TAPB with regard to the total opioid consumption within the first 24 h after surgery. Data regarding patients' characteristics, opioid consumption, pain on the visual analogue scale, operative and anaesthesia induction time, complications and length of stay were collected and analysed. RESULTS: Fifty-five patients were allocated to the L-TAPB and fifty-seven to the U-TAPB. No significant difference was found in the overall dose of opioids within 24 h, and the non-inferiority of the L-TAPB was confirmed. There were almost twice as many patients in the L-TAPB group requesting opioid reserves compared to the U-TAPB group (54.5% vs. 29.8%, P = 0.008). The anaesthesia induction time was significantly longer in the U-TAPB group (17 ± 11 min vs. 23 ± 12 min, P = 0.014). For all other variables (pain on the visual analogue scale, opioid consumption, need of epidural analgesia, operating time, postoperative complications and hospital stay) no statistically significant difference between the L-TAPB and the U-TAPB groups was noted. CONCLUSION: Our results showed the non-inferiority of the laparoscopic delivery compared to ultrasound-guided administration of the TAP block, with the advantage of not affecting anaesthesia times. STUDY REGISTRATION NUMBER: 2017-02017 CE 3294, ClinicalTrials.gov identifier NCT04575233.

Robotic versus laparoscopic liver resections: propensity-matched comparison of two-center experience.

BACKGROUND: The advantages of the robotic approach in minimally invasive liver surgery (MILS) are still debated. This study compares the short-term outcomes between laparoscopic (LLR) and robotic (RLR) liver resections in propensity score matched cohorts. METHODS: Data regarding minimally invasive liver resections in two liver surgery units were retrospectively reviewed. A propensity score matched analysis (1:1 ratio) identified two groups of patients with similar characteristics. Intra- and post-operative outcomes were then compared. The difficulty of MILS was based on the IWATE criteria. RESULTS: Two hundred sixty-nine patients underwent MILS between January 2014 and December 2021 (LLR = 192; RLR = 77). Propensity score matching identified 148 cases (LLR = 74; RLR = 74) consisting of compensated cirrhotic patients (100%) underwent non-anatomic resection of IWATE 1-2 class (90.5%) for a solitary tumor < 5 cm in diameter (93.2%). In such patients, RLRs had shorter operative time (227 vs. 250 min, p = 0.002), shorter Pringle's cumulative time (12 vs. 28 min, p < 0.0001), and less blood loss (137 vs. 209 cc, p = 0.006) vs. LLRs. Conversion rate was nihil (both groups). In RLRs compared to LLRs, R0 rate (93 vs. 96%, p > 0.71) and major morbidity (4.1 vs. 5.4%, p > 0.999) were similar, without post-operative mortality. Hospital stay was shorter in the robotic group (6.2 vs. 6.6, p = 0.0001). CONCLUSION: This study supports the non-inferiority of RLR over LLR. In compensated cirrhotic patients underwent resection of low-to-intermediate difficulty for a solitary nodule < 5 cm, RLR was faster, with less blood loss despite the shorter hilar clamping, and required shorter hospitalization compared to LLR.

Long-term outcomes in elderly patients after elective surgery for colorectal cancer within an ERAS protocol: a retrospective analysis.

PURPOSE: The number of elderly patients with a diagnosis of colorectal cancer (CRC) is increasing. Considering short life expectancy and multiple comorbidities, surgery may not always be the best treatment option. METHODS: We included all consecutive patients aged 80 years and older who underwent elective resection for CRC following Enhanced Recovery after Surgery (ERAS) protocol between January 2011 and May 2021. The primary endpoint was overall survival, secondary endpoints were 30-day morbidity, and the rate of return to pre-operative living conditions 3 months after surgery. RESULTS: Ninety-four patients were included. Mean age was 84.6 ± 3.6 years, 49 patients (52%) were female. Most patients (77.6%) were ASA score ≥ 3. Laparoscopic resections were performed in 85 patients (90.4%), involving 69 (73.4%) colonic and 25 (26.6%) rectal resections. A stoma was constructed in 22 patients (23%), and reversed in 12 (54.5%). Twenty-two patients (23.4%) experienced a Clavien-Dindo ≥ 3 complication, and 2 patients (2.1%) died. The median length of hospital stay was 8 (interquartiles: 6-15) days. Sixty-six patients (70.2%) were discharged home directly and 26 (27.7%) to rehabilitation or postacute care institutes. At three months after surgery, eighty-two patients (96.5%) returned to their pre-operative living conditions directly or after short-term rehabilitation. Mean follow-up was 53 ± 33 months, estimated 5-year overall survival was 60.3% (95%CI 49.5-71.1%), and disease-free survival was 86.3% (95%CI 78.1-94.4%). CONCLUSIONS: Our study suggests that elderly patients undergoing elective surgery have a high potential to return to preoperative living conditions and good overall- and disease-free survivals, despite significant postoperative morbidity.

Transanal (TaTME) vs. laparoscopic total mesorectal excision for mid and low rectal cancer: a propensity score-matched analysis of early and long-term outcomes.

PURPOSE: Transanal total mesorectal excision (TaTME) has been proposed as an alternative to laparoscopic total mesorectal excision (LapTME) in distal rectal tumors. Despite encouraging reports, mid- and long-term oncological results are limited. In this study, we aimed at comparing TaTME versus LapTME in patients with mid and low rectal cancer. METHODS: From January 2012 to December 2019, all patients undergoing either TaTME or LapTME for rectal adenocarcinoma ≤ 12 cm from the anal verge were included. Demographic, clinical, and follow-up data were retrieved from a prospective and audited database, and a propensity score-matched analysis was performed. RESULTS: A total of 144 patients were included, 38 underwent TaTME, and 106 LapTME. The median age was 68.0 (60.2-75.8) years, and 96 (66.7%) patients were male. Median follow-up was 30.6 (20.2-39.8) months in the TaTME group and 49.5 (22.6-68.5) months in the LapTME group. There was one (2.6%) local recurrence in the TaTME group and two (1.9%) in the LapTME group (p = 0.788). There was no difference in the 3-year disease-free survival between groups both in the primary (93% vs. 86%, p = 0.274) and the propensity score-matched analyses (93% vs. 81%, p = 0.132). Conversion to open surgery was less frequent in the TaTME group (none vs. 4 (11.4%), p = 0.041). Intra- and postoperative complications, length of stay, specimen quality, and resection margins were similar between groups. CONCLUSIONS: In our experience, TaTME was associated with a less frequent conversion to open surgery but otherwise had similar post-operative results compared to LapTME. Local recurrence and 3-year survival rates were similar.

Laparoscopic Versus Open Re-operations Within 30 Days After Lower Gastrointestinal Tract Surgery: a Retrospective Comparative Study.

BACKGROUND: Re-operations within 30 days after lower gastrointestinal tract surgery are associated to high morbidity and mortality. Laparoscopic approach has been reported as feasible and safe in selected patients, but comparative data to laparotomy are scarce. The aim of this study was to review our experience in laparoscopic re-operations and compare it to laparotomy. METHODS: From January 2012 to December 2016, patients undergoing a re-operation within one month after lower gastrointestinal tract surgery were included and divided into laparoscopy and laparotomy groups. The primary endpoint was successful re-operation, defined as recovery without any of the following: conversion to laparotomy, need of further invasive treatments or death. Secondary outcomes were the length of hospital stay and 30-day morbidity and mortality. Demographic, clinical and surgical characteristics were collected and analyzed. RESULTS: Out of 114 patients who underwent a re-operation, 71 met the inclusion criteria. Thirty (42%) patients underwent laparoscopy and 41 (58%) laparotomy. Thirty (42%) patients were male and median age was 72.0 years-old. The initial operation was elective in 24 (34%) patients, and 50% of the initial operations were colorectal resections in both groups. Multivariate analyses showed that type of approach did not affect the re-operation success rate. Laparotomy was an independent predictor of prolonged hospital stay (OR 3.582, 95%CI 1.191-10.776, p = 0.023) and mortality (OR 13.123, 95%CI 1.301-131.579, p = 0.029). CONCLUSIONS: Re-operations within 30 days after lower gastrointestinal tract surgery may be safe in selected patients, as effective as laparotomy, and associated with shorter hospital stay and lower mortality rates.

Bowel function recovery after laparoscopic transverse colectomy within an ERAS program: a comparison to right and left colectomy.

BACKGROUND: It is known that functional recovery of the bowel is slower after right colectomy (RC) compared to left colectomy (LC), but very little has been reported on transverse colectomy (TC). OBJECTIVES: The aim of this study was to compare the clinical and early functional outcomes of TC, a more infrequent operation, to RC, and LC for colorectal cancer. METHODS: Between December 2011 and December 2017, all patients undergoing elective colon resection in our institution were treated according to a standardized ERAS protocol and entered in a prospective database. We included in the study patients undergoing laparoscopic TC, RC, or LC for cancer with curative intent. The primary endpoint was prolonged postoperative ileus (PPOI), defined as need to insert a nasogastric tube, or refractory nausea VAS > 4 on or after the third postoperative day. Secondary endpoints were postoperative morbidity and length of hospital stay (LoS). RESULTS: Out of 286 patients, 126 met the inclusion criteria: 20 underwent TC, 65 RC, and 41 LC. Patients in LC group were younger than in TC and RC groups; other baseline demographics were similar. PPOI was observed in 5 (25%), 26 (40%), and 10 (24%) patients in TC, RC, and LC groups, respectively (p = 0.417). In single group comparisons, the incidence of PPOI in the TC group was significantly lower in comparison to the RC group (OR for RC: 4.255, 95% CI 1.092-16.667, p = 0.037) and similar to the LC group. No significant differences in terms of postoperative complications or LoS stay were observed. CONCLUSION: The incidence of PPOI after segmental laparoscopic colectomy for cancer within an ERAS program appears as infrequent in TC as in LC and lower than after RC. It may be reasonable to consider a slower oral intake after RC, as it represents an independent predictor of PPOI.

Conservative Sinusectomy vs. excision and primary off-midline closure for pilonidal disease: a randomized controlled trial.

PURPOSE: Pilonidal sinus disease (PD) is a common acquired disease, responsible for discomfort and time off work. There is currently no consensus on the best surgical therapy. We aimed at comparing conservative sinusectomy (S) to excision and paramedian primary closure (PC). METHODS: This is a randomized controlled trial compatible with the CONSORT statement standards. We included all patients with chronic PD between 2012 and 2017. We excluded patients with acute abscesses, recurrent PD after surgery with a curative intent and patients needing complex reconstructions with rotation flaps. Patients with chronic symptomatic PD were randomized to S or PC. Primary end-point was the rate of patients healed at 3 weeks, secondary outcomes were total healing time, pain, time off work, patient satisfaction and recurrence at 1 year. Patients were seen at a wound clinic until healed and contacted at 3, 6, and 12 months for follow-up. RESULTS: After inclusion of 58 patients the study was stopped prematurely due to discrepancy between expected and observed outcomes. Only 4/30 (13.3%) patients in the S group had healed completely at 3 weeks compared with 14/28 (50%) in the PC group (p = 0.01). Median time to complete healing was 54 (23-328) days in the S group compared to 34 (13-141) in the PC group (p = 0.025). Number of outpatient visits, time off work, analgesia requirement, and recurrence rates at 12 months 4 (16%) in the S group and 3 (11.1%) in the PC group (p = 0.548) were similar. CONCLUSIONS: PC leads to faster healing compared to S, with similar healthcare burden. TRIAL REGISTRATION: The study was approved by the local ethics committee and registered in www.clinicaltrials.gov (REF: NCT03271996). The study was carried out at the Regional Hospital of Lugano, Switzerland.

Correction to: Conservative Sinusectomy vs. excision and primary off-midline closure for pilonidal disease: a randomized controlled trial.

The original version of this article, unfortunately, contained an error. The given names and family names of the authors were interchanged and are now presented correctly. The original article has been corrected.].

ERAS, length of stay and private insurance: a retrospective study.

PURPOSE: Hospital discharge after colorectal resection within an Enhanced Recovery After Surgery (ERAS) program occurs earlier compared to standard-care postoperative pathways but often later than what objective criteria of "readiness for discharge" could allow. The aim of this study was to analyse reasons and risk factors of such discharge delay. METHODS: All elective patients admitted for colorectal resection at the regional Hospital of Lugano in 2014 and 2015 were included. The postoperative day on which patients fulfilled consensus agreed criteria (according to Fiore) for readiness for discharge (POD-F) and the effective day of discharge (POD-D) were determined. We analysed the reasons for discharge delay (POD-D>POD-F) and performed univariate and multivariate analysis to determine risk factors. RESULTS: One hundred thirty-eight patients were included in the study. Median POD-F was 5 (2-48) days, POD-D was 6 (3-50) days. In 94 patients, POD-D occurred later than POD-F with a median delay of 1 (1-11) days. Reasons for discharge delay were insufficient social support in 13 (14%), patient's preference in 39 (41%) and medical team preference in 41 (44%). Private insurance (OR 2.61, 95%CI 1.08-6.34, p = 0.034) and patient discharged on a day other than Monday (OR 2.94, 95%CI 1.16-7.14, p = 0.023) were independent predictors for discharge delay. CONCLUSION: Even when objective criteria for readiness for discharge have been fulfilled, patients and/or doctors often do not feel comfortable with hospital discharge at this time point. Length of stay, even within an ERAS program, is still influenced by several non-medical factors and is therefore not a precise surrogate marker of outcomes.

Prospective assessment of trocar-specific morbidity in laparoscopy.

BACKGROUND: The purpose of the present study was to challenge the hypothetical advantage of single port laparoscopy (SPL) over conventional laparoscopy by measuring prospectively the morbidity specifically related to conventional trocar sites (TS). METHODS: From November 2010 to December 2011, 300 patients undergoing various laparoscopic procedures were enrolled. Patient, surgery, and trocar characteristics were recorded. We evaluated at three time points (in-hospital and at 1 and 6 months postoperatively) specifically for each TS, pain (Visual Analog Scale), morbidity (infection, hematoma, hernia), and cosmesis (Patient Scar Assessment Score; PSAS). Patients designated their "worst TS," and a composite endpoint "bad TS" was defined to include any adverse outcome at a TS. RESULTS: We analyzed 1,074 TS. Follow-up was >90 %. Pain scores of >3/10 at 1 and 6 months postoperatively, were reported by 3 and 1 % of patients at the 5 mm TS and by 9 and 1 % at the larger TS, respectively (5 mm TS vs larger TS; p = 0.001). Pain was significantly lower for TS located in the lower abdomen than for the upper abdomen or the umbilicus (p = 0.001). The overall complication rate was <1 % and significantly lower for the 5 mm TS (hematoma p = 0.046; infection p = 0.0001). No hernia was found. The overall PSAS score was low and significantly lower for the 5 mm TS (p = 0.0001). Significant predictors of "bad TS" were larger TS (p = 0.001), umbilical position (p = 0.0001), emergency surgery (p = 0.0001), accidental trocar exit (p = 0.022), fascia closure (p = 0.006), and specimen extraction site (p = 0.0001). CONCLUSIONS: Specific trocar morbidity is low and almost negligible for 5 mm trocars. The umbilicus appears to be an unfavorable TS.

Identification of TPM2 and CNN1 as Novel Prognostic Markers in Functionally Characterized Human Colon Cancer-Associated Stromal Cells.

Stromal infiltration is associated with poor prognosis in human colon cancers. However, the high heterogeneity of human tumor-associated stromal cells (TASCs) hampers a clear identification of specific markers of prognostic relevance. To address these issues, we established short-term cultures of TASCs and matched healthy mucosa-associated stromal cells (MASCs) from human primary colon cancers and, upon characterization of their phenotypic and functional profiles in vitro and in vivo, we identified differentially expressed markers by proteomic analysis and evaluated their prognostic significance. TASCs were characterized by higher proliferation and differentiation potential, and enhanced expression of mesenchymal stem cell markers, as compared to MASCs. TASC triggered epithelial-mesenchymal transition (EMT) in tumor cells in vitro and promoted their metastatic spread in vivo, as assessed in an orthotopic mouse model. Proteomic analysis of matched TASCs and MASCs identified a panel of markers preferentially expressed in TASCs. The expression of genes encoding two of them, calponin 1 (CNN1) and tropomyosin beta chain isoform 2 (TPM2), was significantly associated with poor outcome in independent databases and outperformed the prognostic significance of currently proposed TASC markers. The newly identified markers may improve prognostication of primary colon cancers and identification of patients at risk.

A Pilot, Prospective, Observational Study to Investigate the Value of NGS in Liquid Biopsies to Predict Tumor Response After Neoadjuvant Chemo-Radiotherapy in Patients With Locally Advanced Rectal Cancer: The LiBReCa Study.

Introduction: Circulating tumor DNA (ctDNA) correlates with the response to therapy in different types of cancer. However, in patients with locally advanced rectal cancer (LARC), little is known about how ctDNA levels change with neoadjuvant chemoradiation (Na-ChRT) and how they correlate with treatment response. This work aimed to explore the value of serial liquid biopsies in monitoring response after Na-ChRT with the hypothesis that this could become a reliable biomarker to identify patients with a complete response, candidates for non-operative management. Materials and Methods: Twenty-five consecutive LARC patients undergoing long-term Na-ChRT therapy were included. Applying next-generation sequencing (NGS), we characterized DNA extracted from formalin-fixed paraffin embedded diagnostic biopsy and resection tissue and plasma ctDNA collected at the following time points: the first and last days of radiotherapy (T0, Tend), at 4 (T4), 7 (T7) weeks after radiotherapy, on the day of surgery (Top), and 3-7 days after surgery (Tpost-op). On the day of surgery, a mesenteric vein sample was also collected (TIMV). The relationship between the ctDNA at those time-points and the tumor regression grade (TRG) of the surgical specimen was statistically explored. Results: We found no association between the disappearance of ctDNA mutations in plasma samples and pathological complete response (TRG1) as ctDNA was undetectable in the majority of patients from Tend on. However, we observed that the poor (TRG 4) response to Na-ChRT was significantly associated with a positive liquid biopsy at the Top. Conclusions: ctDNA evaluation by NGS technology may identify LARC patients with poor response to Na-ChRT. In contrast, this technique does not seem useful for identifying patients prone to developing a complete response.

Ultrasound-Guided Pudendal Nerve Block in Patients Undergoing Open Hemorrhoidectomy: A Post-Hoc Cost-Effectiveness Analysis from a Double-Blind Randomized Controlled Trial.

BACKGROUND: Pudendal nerve block (PNB) has been demonstrated to reduce postoperative pain and re-admission rates after open hemorrhoidectomy and may reduce costs but, to date, no study has reported data on this aspect. The aim of our study was to perform a cost analysis on PNB use in in- and outpatients undergoing open hemorrhoidectomy. METHODS: From January 2018 to December 2019, patients undergoing open hemorrhoidectomy were included and randomized to undergo spinal anesthesia either with or without the PNB. Clinical data, direct and indirect costs for in- and outpatients, operating time and operating theatre occupancy were recorded. A cost-effectiveness analysis based on the diagnosis-related groups (DRG) and TARMED reimbursement systems was performed. RESULTS: Patients who underwent PNB in addition to spinal anesthesia had significantly less pain and a shorter length of hospital stay after open hemorrhoidectomy. The cost analysis included all 49 patients, 23 of whom, in addition to spinal anesthesia, received a PNB. There were no significant differences in operating theatre occupancy (p=0.662), mean operative time (p=0.610) or time required for anesthesia (p=0.124). Direct costs were comparable (482±386 vs 613±543 EUR, p=0.108), while indirect costs were significantly lower in the PNB group (2606±816 vs 2769±1506 EUR, p=0.005). We estimated an incremental cost-effectiveness ratio (ICER) of -243 ± 881 EUR/pain unit on the VAS. CONCLUSION: Despite limitations, the ultrasound-guided PNB seems to reduce costs in patient undergoing open hemorrhoidectomy under spinal anesthesia. It was shown to be clinically beneficial and cost-effective, and therefore recommendable in patients undergoing open hemorrhoidectomy.

Characteristics of Early-Onset vs Late-Onset Colorectal Cancer: A Review.

Importance: The incidence of early-onset colorectal cancer (younger than 50 years) is rising globally, the reasons for which are unclear. It appears to represent a unique disease process with different clinical, pathological, and molecular characteristics compared with late-onset colorectal cancer. Data on oncological outcomes are limited, and sensitivity to conventional neoadjuvant and adjuvant therapy regimens appear to be unknown. The purpose of this review is to summarize the available literature on early-onset colorectal cancer. Observations: Within the next decade, it is estimated that 1 in 10 colon cancers and 1 in 4 rectal cancers will be diagnosed in adults younger than 50 years. Potential risk factors include a Westernized diet, obesity, antibiotic usage, and alterations in the gut microbiome. Although genetic predisposition plays a role, most cases are sporadic. The full spectrum of germline and somatic sequence variations implicated remains unknown. Younger patients typically present with descending colonic or rectal cancer, advanced disease stage, and unfavorable histopathological features. Despite being more likely to receive neoadjuvant and adjuvant therapy, patients with early-onset disease demonstrate comparable oncological outcomes with their older counterparts. Conclusions and Relevance: The clinicopathological features, underlying molecular profiles, and drivers of early-onset colorectal cancer differ from those of late-onset disease. Standardized, age-specific preventive, screening, diagnostic, and therapeutic strategies are required to optimize outcomes.