Search Results (149)

Background: Colorectal liver metastasis (CRLM) represents a major clinical challenge in oncology, affecting 25–50% of colorectal cancer patients and significantly impacting survival. While multimodal therapies—including surgical resection, systemic chemotherapy, and local ablative techniques—have improved outcomes, prognosis remains heterogeneous due to variations in tumor biology, patient factors, and institutional practices. Methods: This review synthesizes current evidence on prognostic factors influencing CRLM management, encompassing clinical (e.g., tumor burden, anatomic distribution, timing of metastases), biological (e.g., CEA levels, inflammatory markers), and molecular (e.g., RAS/BRAF mutations, MSI status, HER2 alterations) determinants. Results: Key findings highlight the critical role of molecular profiling in guiding therapeutic decisions, with RAS/BRAF mutations predicting resistance to anti-EGFR therapies and MSI-H status indicating potential responsiveness to immunotherapy. Emerging tools like circulating tumor DNA (ctDNA) and radiomics offer promise for dynamic risk stratification and early recurrence detection, while the gut microbiome is increasingly recognized as a modulator of treatment response. Conclusions: Despite advancements, challenges persist in standardizing resectability criteria and integrating multidisciplinary approaches. Current guidelines (NCCN, ESMO, ASCO) emphasize personalized strategies but lack granularity in terms of incorporating novel biomarkers. This exhaustive review underscores the imperative for the development of a unified, biomarker-integrated framework to refine CRLM management and improve long-term outcomes. Full article

Background and Objectives: The technique of complete mesocolic excision (CME) for colonic cancer is being advocated to improve the local control of the disease and increase the long-term survival. However, even with an open approach, CME is a complex technique and has not yet been adopted as standard care. Laparoscopy has been proven to bring significant advantages to colorectal surgery but performing a laparoscopic CME (Lap-CME) for colonic cancer is even more technically demanding than CME in open surgery. The purpose of this study is to evaluate whether Lap-CME can be offered as a standard procedure for patients with colonic cancer and to compare the results with those obtained after a conventional, open technique. Materials and methods: This study included 100 consecutive patients with colonic cancer, who were operated on by the same surgical team using a standardized medial-to-lateral open or laparoscopic complete mesocolic excision technique. The perioperative data was prospectively recorded in a database and retrospectively analyzed with the aim of identifying the proportion of patients that received Lap-CME, to evaluate the success rate of the procedure and to identify whether there are differences in the oncological quality of CME between the laparoscopic and open surgery groups. Results: Most of the patients enrolled in this study were in the advanced stages of the disease, with the incidence of pT3 tumors being 67% and the mean tumor size averaging 4.5 cm. Laparoscopic CME was performed in 39% of cases overall, with 41.4% being right colectomies, 42.5% being left colectomies and 16.1% being transverse colectomies. All of the parameters relevant to the oncological quality of resection, namely total lymph node count, resection margins, or the completeness of resection, were similar between the open and laparoscopic groups both when analyzed for the entire cohort or when analyzed for specific subgroups according to the tumor location (right, transverse, or left colon) or stage of the disease (pT3 or stage III). Conclusions: Laparoscopic complete mesocolic excision for colonic cancer can be offered as a standard procedure by experienced surgical teams in carefully selected patients and provides oncological results similar to those obtained with open surgery. Full article

Rectal cancer management necessitates a rigorous multidisciplinary strategy, emphasizing precise staging and detailed risk stratification to inform optimal therapeutic decision-making. Obtaining an accurate histological diagnosis before initiating treatment is essential. Comprehensive staging integrates clinical evaluation, thorough medical history analysis, assessment of carcinoembryonic antigen (CEA) levels, and computed tomography (CT) imaging of the abdomen and thorax. High-resolution pelvic magnetic resonance imaging (MRI), utilizing dedicated rectal protocols, is critical for identifying recurrence risks and delineating precise anatomical relationships. Endoscopic ultrasound further refines staging accuracy by determining the tumor infiltration depth in early-stage cancers, while preoperative colonoscopy effectively identifies synchronous colorectal lesions. In early-stage rectal cancers (T1–T2, N0, and M0), radical surgical resection remains the standard of care, although transanal local excision can be selectively indicated for certain T1N0 tumors. In contrast, locally advanced rectal cancers (T3, T4, and N+) characterized by microsatellite stability or proficient mismatch repair are optimally managed with total neoadjuvant therapy (TNT), which combines chemoradiotherapy with oxaliplatin-based systemic chemotherapy. Additionally, tumors exhibiting high microsatellite instability or mismatch repair deficiency respond favorably to immune checkpoint inhibitors (ICIs). The evaluation of tumor response following neoadjuvant therapy, utilizing MRI and endoscopic assessments, facilitates individualized treatment planning, including non-operative approaches for patients with confirmed complete clinical responses who comply with rigorous follow-up. Recent advancements in molecular characterization, targeted therapies, and immunotherapy highlight a significant evolution towards personalized medicine. The effective integration of these innovations requires enhanced interdisciplinary collaboration to improve patient prognosis and quality of life. Full article

The diagnosis of colorectal cancer in more advanced stages, especially in younger patients where the diagnosis usually occurs because of obstructive complications, has prompted the development of less invasive, more rapid and well tolerated methods of decompression as an alternative to the standard surgical approach. As such, self-expanding metal stents (SEMSs) have gained wide acceptance for the palliative alleviation of obstructive symptoms in patients with advanced colorectal cancer. The purpose of this study was to evaluate SEMS placement against various forms of palliative surgical procedures in terms of effectiveness, morbidity, mortality and oncologic results. We conducted a systematic search of PubMed, Web of Science, Cochrane Library and Medline for articles describing patients with incurable locally advanced obstructive colorectal cancer who underwent surgery or self-expanding metal stent placement as a palliative procedure for the alleviation of symptoms. Eighteen studies (1606 patients) were included in a pooled meta-analysis. In the surgery group the clinical success was slightly higher (98.62% vs. 94.92%; OR = 0.35, 95%CI [0.16–0.73], p = 0.005) and the late complications rate was lower (13.9% vs. 24.0%; OR = 3.01, 95%CI [2.06–4.39], p < 0.00001). The SEMS placement was associated with a lower early complication (11.3% vs. 28.1%; OR = 0.34, 95%CI [0.19–0.58], p = 0.0001) and a shorter length of hospital stay (SMD = −1.94, 95%CI [−2.76, −1.12], p < 0.00001). In terms of the oncologic results, surgery was significantly associated with an increased overall survival regardless of the type of procedure (OR = 1.24, 95%CI [1.08–1.42], p = 0.002). Although having lower early morbidity and mortality rates, SEMS placement was associated with an increased chance of late complications and a worse overall survival, thus making them avoidable when patients have longer life expectancies. Due to the lower early complications rates, SEMSs might still have a place in the management of selected cases with bowel obstruction. Full article

Background: Colorectal cancer (CRC) remains one of the most prevalent and fatal malignancies globally, with radiotherapy playing a crucial role in the treatment of locally advanced rectal cancer (LARC). However, the efficacy of radiotherapy is limited by significant resistance, with only a small proportion of patients achieving a pathologic complete response (PCR) to neoadjuvant chemoradiotherapy (nCRT). This study aims to uncover the genetic and molecular factors contributing to radiotherapy resistance in CRC through an integrated analysis of germline mutations, transcriptomic data, and immune microenvironment characteristics. Methods: Whole-exome sequencing (WES) was performed on tumor samples from 12 LARC patients. Transcriptomic data from the TCGA-READ and GSE150082 (LARC with chemoradiotherapy) cohorts were integrated with WES findings. The independent cohort GSE190826 (neoadjuvant therapy in rectal cancer) dataset was utilized to validate the WES data. Single-cell RNA sequencing (scRNA-seq) analysis of GSE132465 (primary CRC) resolved cellular heterogeneity. A random forest algorithm was employed to develop a predictive gene signature. Results: Our findings reveal a mutational landscape associated with radiotherapy resistance, identifying specific germline mutations linked to treatment outcomes. Differential gene expression analysis highlighted pathways involved in DNA replication, DNA repair, and immune regulation, with a focus on the tumor immune microenvironment (TIME). A gene signature, including CDCA4, FANCA, PBRM1, RPL13, and C12orf43, was developed to predict radiotherapy response. Notably, CDCA4 expression was significantly associated with tumor mutation burden (TMB) and microsatellite instability (MSI), and it plays a crucial role in regulating B cell infiltration in the tumor microenvironment. Conclusions: Our study provides novel insights into the molecular mechanisms of radiotherapy resistance in CRC and proposes CDCA4 and B cell-related immune features as potential biomarkers for patient stratification and personalized treatment strategies. Full article

Background: Colorectal cancer (CRC) is a term that refers to the combination of colon and rectal cancer as they are being treated as a single tumor. In CRC, 72% of tumors are colon cancer, while the other 28% represent rectal cancer. CRC is a multifactorial disease caused by both genetic and epigenetic changes in the colon mucosal cells, affecting the oncogenes, DNA repair genes, and tumor suppressor genes. Currently, two DNA methylation-based biomarkers for CRC have received FDA approval: SEPT9, used in blood-based screening tests, and a combination of NDRG4 and BMP3 for stool-based tests. Although DNA methylation biomarkers have been explored in colorectal cancer (CRC), the identification of robust and clinically valuable biomarkers remains a challenge, particularly for early-stage detection and precancerous lesions. Patients often receive diagnoses at the locally advanced stage, which limits the potential utility of current biomarkers in clinical settings. Methods: The datasets used in this study were retrieved from the GEO database, specifically GSE75548 and GSE75546 for rectal cancer and GSE50760 and GSE101764 for colon cancer, summing up to a total of 130 paired samples. These datasets represent expression profiling by array, methylation profiling by genome tiling array, and expression profiling by high-throughput sequencing and include rectal and colon cancer samples paired with adjacent normal tissue samples. Differential analysis was used to identify differentially methylated CPG sites (DMCs) and identify differentially expressed genes (DEGs). Results: From the integration of DMCs with DEGs in colorectal cancer, we identified 150 candidates for methylation-regulated genes (MRGs) with two genes common across all cohorts (GNG7 and PDX1) highlighted as candidate biomarkers in CRC. The functional enrichment analysis and protein–protein interactions (PPIs) identified relevant pathways involved in CRC, including the Wnt signaling pathway, extracellular matrix (ECM) organization, among other enriched pathways. Conclusions: Our findings show the strength of our in silco computational approach in jointly identifying methylation-regulated biomarkers for colon cancer and highlight several genes and pathways as biomarker candidates for further investigations. Full article

Oligometastatic colorectal cancer (CRC) refers to a state in which distant metastatic spread is limited to a few sites, offering the potential for curative treatment with aggressive local therapies. The surgical management of oligometastatic CRC has gained increasing attention due to its potential to improve survival. This review explores the evolving role of surgery in the treatment of oligometastatic disease, focusing on the criteria for selecting patients, surgical techniques, and outcomes. While systemic therapy remains essential, surgery can offer long-term survival benefits for appropriately selected patients with limited metastatic disease, particularly those with metastases confined to the liver. Advances in imaging technologies, minimally invasive surgical techniques, and perioperative care have enhanced the safety and efficacy of these procedures. The integration of multimodal therapies, such as chemotherapy, targeted therapy, and immunotherapy, in conjunction with surgery, is also discussed, with a focus on optimizing outcomes. To conclude, surgical resection of liver metastases improves survival compared to systemic therapy alone; thus, resection should be taken into consideration whenever possible. For initially unresectable diseases, personalized conversion therapy is indicated. This review aims to clarify how and when liver resection can first be chosen; when preoperative systemic treatment is needed; and if this is chosen, what is the best approach. Full article

Background and Objectives: Conversion surgery for liver metastatic colorectal cancer (mCRC) has been associated with prolonged survival. This study aimed to evaluate the efficacy and safety of integrating biological therapies with fluorouracil-based induction chemotherapy in patients with isolated liver mCRC who subsequently underwent curative resection of both the primary tumor and liver metastases. Materials and Methods: This multicenter, retrospective study, conducted by the Turkish Oncology Group (TOG), included 116 patients from 11 tertiary centers who underwent conversion surgery following induction chemotherapy between 2009 and 2024. Results: The median age was 57 years, with 62% male patients. The median follow-up period was 55.3 months. The median progression-free survival (PFS) and overall survival (OS) were 21.1 and 53.7 months, respectively. No significant differences in PFS or OS were observed based on biological therapy use or tumor localization. Among patients with RAS/RAF wild-type tumors, PFS and OS were comparable between those receiving Anti-EGFR and Anti-VEGF therapy. In RAS/RAF mutant tumors, the addition of Anti-VEGF therapy did not confer a survival benefit. Factors associated with shorter PFS included advanced tumor stage (ypT3-T4), lymph node metastasis, and multiple metastases, while shorter OS was linked to advanced tumor stage and lack of objective response. Conclusions: Surgical resection plays a pivotal role in improving survival outcomes in patients with potentially resectable liver mCRC. Optimizing induction chemotherapy regimens may enhance conversion rates and prolong long-term survival. Further studies are needed to refine treatment selection based on tumor localization, mutation status, and molecular biomarkers. Full article

Nectins constitute a family of Ca(2+)-independent immunoglobulin-like adhesion molecules. They are involved in cell proliferation, morphogenesis, growth, development, and immune modulation. Due to their broad involvement in physiological processes, extensive research is being conducted on the expression of individual nectins in a variety of cancers and their potential in diagnosis, prognosis, and treatment. The overexpression of nectin-1 may be a poor prognostic factor in gastrointestinal cancers (intestine and pancreas). Similarly, the overexpression of nectin-2 is a worse prognostic factor (greater tumor advancement and shorter patient survival) in cancers such as gallbladder, esophagus, and breast cancer. Changes in nectin-3 expression also affect the advancement of, e.g., colorectal cancer. Additionally, a significant factor here seems to be the change in the localization of nectin-3 expression within cellular structures. The most extensively studied nectin-4 also shows prognostic potential in many cancers. Most often, its high expression correlates with poor prognosis (e.g., gastric cancer), but it may also be a positive prognostic factor, e.g., in salivary gland cancer. Therapy based on nectin-4 is already known and used in the case of urothelial cancers. The expression of nectin-like protein 5 (necl-5) also shows prognostic and therapeutic potential in pancreatic and lung cancers, as well as in multiple myeloma. Full article

The Eastern Canadian Gastrointestinal Cancer Consensus Conference was an annual meeting that was held in St. John’s, Newfoundland and Labrador, from 26 to 28 September 2024. This included experts in medical oncology, radiation oncology, surgical oncology, nuclear medicine, and general practitioners in oncology (GPO) from across the eastern Canadian provinces who are involved in the management of patients with gastrointestinal malignancies. This consensus statement generated by the conference addresses multiple topics, including the management of localized rectal cancer, liver-limited colorectal cancer, systemic therapy for advanced biliary tract cancers, radioligand therapy for gastroenteropancreatic neuroendocrine tumors (GEP-NETs), systemic therapy for pancreatic and midgut well-differentiated NETs, and systemic therapy for HER2-positive gastroesophageal cancers. Full article

Background/Objectives: Rectal cancer is a major global health issue with high morbidity and mortality rates. Local recurrence (LR) significantly impacts patient outcomes, decreasing survival rates and often necessitating extensive secondary treatments. While robot-assisted total mesorectal excision (R-TME) is becoming a preferred method for rectal cancer surgery due to its improved precision and visualisation, long-term data on LR and predictors of recurrence remain limited. This study aims to determine the 3-year LR rate following R-TME and to identify predictors of recurrence to enhance patient selection and the personalisation of treatment. Methods: This retrospective international multicentre cohort study included 1039 consecutive rectal cancer patients who underwent R-TME between 2013 and 2020, with a minimum of 3 years of follow-up. Data from tertiary colorectal centres in the United Kingdom, the Netherlands, Spain, France, Italy, and Belgium were analysed. Potential predictors of LR were identified using backward elimination, and four machine learning models were evaluated for predicting LR. Results: The 3-year LR rate was 3.8%. Significant predictors of LR included advanced clinical M-staging, length of the hospital stay, postoperative ileus, postoperative complications, pathological N-staging, the completeness of resection, and the resection margin distance. The eXtreme Gradient Boosting model performed best for LR prediction, with a final accuracy of 77.1% and an AUC of 0.76. Conclusions: R-TME in high-volume centres achieves low 3-year LR rates, suggesting that robot-assisted surgery offers oncological safety and advantages in rectal cancer management. This study underscores the importance of surgical precision, patient selection, and standardised perioperative care, supporting further investment in robotic training to improve long-term patient outcomes. Full article

Over the past two decades, surgical techniques in colorectal cancer (CRC) have improved patient outcomes through precision and reduced invasiveness. Open colectomy, laparoscopic surgery, robotic-assisted procedures, and advanced rectal cancer treatments such as total mesorectal excision (TME) and transanal TME are discussed in this article. Traditional open colectomy offers reliable resection but takes longer to recover. Laparoscopic surgery transformed CRC care by improving oncological outcomes, postoperative pain, and recovery. Automated surgery improves laparoscopy’s dexterity, precision, and 3D visualisation, making it ideal for rectal cancer pelvic dissections. TME is the gold standard treatment for rectal cancer, minimising local recurrence, while TaTME improves access for low-lying tumours, preserving the sphincter. In metastatic CRC, palliative procedures help manage blockage, perforation, and bleeding. Clinical examples and landmark trials show each technique’s efficacy in personalised care. Advanced surgical techniques and multidisciplinary approaches have improved CRC survival and quality of life. Advances in CRC treatment require creativity and customised surgery. Full article

Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide, necessitating the continuous evolution of therapeutic approaches. Despite advancements in early detection and localized treatments, metastatic colorectal cancer (mCRC) poses significant challenges due to low survival rates and resistance to conventional therapies. This review highlights the current landscape of CRC treatment, focusing on chemotherapy and targeted therapies. Chemotherapeutic agents, including 5-fluorouracil, irinotecan, and oxaliplatin, have significantly improved survival but face limitations such as systemic toxicity and resistance. Targeted therapies, leveraging mechanisms like VEGF, EGFR, and Hedgehog pathway inhibition, offer promising alternatives, minimizing damage to healthy tissues while enhancing therapeutic precision. Furthermore, future directions in CRC treatment include exploring innovative targets such as Wnt/β-catenin, Notch, and TGF-β pathways, alongside IGF/IGF1R inhibition. These emerging strategies aim to address drug resistance and improve patient outcomes. This review emphasizes the importance of integrating molecular insights into drug development, advocating for a more personalized approach to combat CRC’s complexity and heterogeneity. Full article

Background: A strong body of evidence exists demonstrating deleterious relationships between abnormal body composition (BC) and outcomes in non-complex colorectal cancer. Complex rectal cancer (RC) includes locally advanced and locally recurrent tumours. This scoping review aims to summarise the current evidence examining BC in complex RC. Methods: A literature search was performed on Ovid MEDLINE, EMBASE, and Cochrane databases. Original studies examining BC in adult patients with complex RC were included. Two authors undertook screening and full-text reviews. Results: Thirty-five studies were included. Muscle quantity was the most commonly studied BC metric, with sarcopenia appearing to predict mortality, recurrence, neoadjuvant therapy outcomes, and postoperative complications. In particular, 10 studies examined relationships between BC and neoadjuvant therapy response, with six showing a significant association with sarcopenia. Only one study examined interventions for improving BC in patients with complex RC, and only one study specifically examined patients undergoing pelvic exenteration. Marked variation was also observed in terms of how BC was quantified, both in terms of anatomical location and how cut-off values were defined. Conclusions: Sarcopenia appears to predict mortality and recurrence in complex RC. An opportunity exists for a meta-analysis examining poorer BC and neoadjuvant therapy outcomes. There is a paucity of studies examining interventions for poor BC. Further research examining BC specifically in patients undergoing pelvic exenteration surgery is also lacking. Pitfalls identified include variances in how BC is measured on computed tomography and whether external cut-off values for muscle and adipose tissue are appropriate for a particular study population. Full article

Patients with long-standing inflammatory bowel disease (IBD) involving the colon are at higher risk of developing colorectal dysplastic or neoplastic lesions. While from sporadic colorectal cancer follows an “adenoma-carcinoma” sequence, IBD colitis-associated carcinogenesis is mainly related to an “inflammation-dysplasia-carcinoma” sequence. Currently, specific endoscopic surveillance strategies involving dye spray and virtual chromoendoscopy have been standardized, aiming for early CRC diagnosis. When detected, colitis-associated dysplasia should be classified according to standard classification, thus allowing for better treatment. Indeed, most IBD-associated dysplastic lesions can be treated with endoscopic resection, even though available procedures are usually more challenging than those in the general population. The higher frequency of severe submucosal fibrosis and the difficulty in the definition of lesions’ margins account for this issue. Current endoscopic resection techniques include polypectomy, endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). Recent evidence suggests the relevance of en bloc resection, as this may be associated with lower rates of recurrence. Therefore, particularly for larger (>20 mm) lesions, ESD should be preferred, even though it is considered the most difficult technique due to frequent severe submucosal fibrosis. Considering the growing number of new endoscopic resective techniques, including underwater EMR or ESD, which in the general population have been suggested to lower procedure-related risks and may also allow a larger spread of advanced endoscopic resection in IBD. However, additional data are needed to assess the medium- and long-term efficacy of endoscopic resection of visible dysplasia in IBD patients, which are burdened by a high risk of local and, more importantly, metachronous recurrence. Full article