Colorectal Metastases Research Articles

Early compliance to enhanced recovery protocol as a predictor of complications after liver surgery.

Enhanced Recovery Protocol (ERP) has the purpose of minimising postoperative hospitalisation and expediting the restoration of preoperative patient conditions. This study seeks to investigate the correlation between early non-compliance to postoperative items within ERP and complications in liver surgery. From January 2019 to December 2022 the ERP was proposed to all consecutive patients undergoing liver surgery. Nasogastric tube removal, resuming oral intake and mobilisation and obtaining an adequate glycaemic control were the postoperative items considered as non-compliance indicators. Data were prospectively collected and analysed. 192 patients were included, comprising 99(51.6%) hepatocellular carcinoma, 58(30.2%) colorectal metastasis and 24(12.5%) benign/other pathology. A minimally invasive approach was adopted in 57.3% of cases. Postoperative morbidities occurred in 44.8% of patients, while major complications in 13% of patients. Cirrhosis (p < 0.001), minimally invasive approach (p < 0.004), early oral intake (p < 0.019) and early mobilisation (p < 0.019) significantly correlated to morbidity at multivariate analysis. The complication rate escalated from 26.9% in fully compliant patients, to 58% in patients with two non-compliance indicators and to 91.2% in fully non-compliant patients (p < 0.001). The same trend was confirmed for major complications (p < 0.001). Early non-compliance to ERP postoperative items in liver surgery was significantly associated with overall and major morbidity.

DNA methylation-induced suppression of PRDM16 in colorectal cancer metastasis through the PPARγ/EMT pathway.

DNA methylation-induced suppression of PRDM16 in colorectal cancer metastasis through the PPARγ/EMT pathway.

Interdependent roles for growth differentiation factor-15 (GDF15) and LIMS1 in regulating cell migration: Implications for colorectal cancer metastasis.

Interdependent roles for growth differentiation factor-15 (GDF15) and LIMS1 in regulating cell migration: Implications for colorectal cancer metastasis.

Postoperative changes in body composition after laparoscopic and open resection of colorectal liver metastases: data from the randomized OSLO-COMET trial.

Low muscle mass is negatively associated with survival in patients undergoing surgery for colorectal cancer. Current evidence is limited regarding whether the surgical approach for liver resection of colorectal metastasis impacts postoperative changes in body composition and whether preoperative body composition can impact complication rate and survival. This study included patients previously included in the randomized OSLO-COMET trail where patients was allocated to laparoscopic or open liver resection for colorectal liver metastasis. CT scans 0-3months before and 2-6months after liver resection were segmented with the artificial intelligence-based tool BodySegAI to measure skeletal muscle mass (SM), visceral adipose tissue (VAT), and inter- and intramuscular adipose tissue (IMAT). SM, VAT and IMAT was compared between the open and laparoscopic group and as predictors for 5-year survival and postoperative complications. This study included 216 patients, median age was 67, 127 (59%) were male, 91 (42%) had primary tumor in rectum and 86 (40%) had multiple liver metastasis. There was no significant difference in postoperative change in SM, VAT or IMAT between those undergoing laparoscopy or open surgery. In multivariate analysis, high preoperative IMAT was a predictor for increased risk of postoperative complications (HR (95% CI): 1.045 (CI 95%: 1.003-1.089), p = 0.034). Moreover, postoperative increase in IMAT was a negative predictor for 5-year survival (HR (95%CI):1.009 (1.003-1.016), p = 0.003). Postoperative change in body composition did not differ between patients randomly assigned to open or laparoscopic liver resection for colorectal metastasis. High preoperative IMAT was associated with an increased risk of postoperative complications.

Eyelid and Parotid Gland Metastasis of Colorectal Cancer Demonstrated by 18F-FDG PET/CT.

A 67-year-old man underwent a sigmoid colectomy and received 4 cycles of capecitabine and oxaliplatin. 18F-FDG was performed for the treatment response evaluation. It revealed increased radiotracer uptake both in the nodular lesion of the left parotid gland and in the subcutaneous density of the left eyelid. These lesions were reported as colorectal carcinoma metastasis in immunohistochemical evaluation. Herein, we present an extremely rare case of simultaneous metastasis of both the eyelid and the left parotid gland in a patient who underwent surgery for colorectal cancer.

Withaferin-A Inhibits Colorectal Cancer Growth and Metastasis By Targeting the HSP90/HIF-1α/EMT axis

Withaferin-A Inhibits Colorectal Cancer Growth and Metastasis By Targeting the HSP90/HIF-1α/EMT axis

Cancer-secreted exosomal miR-1825 induces angiogenesis to promote colorectal cancer metastasis

BackgroundAngiogenesis is one of the important factors related to tumorigenesis, invasion, and metastasis. Cancer-secreted exosomes are essential mediators of intercellular cross-talk and participate in angiogenesis and metastasis. Unveiling the mechanism of angiogenesis is an important way to develop anti-angiogenesis therapeutic strategies to against cancer progression.MethodsmiR-1825 expression and relationship with microvascular density were validated in colorectal cancer (CRC) by in situ hybridization (ISH) staining and immunohistochemistry (IHC). Sequential differential centrifugation, transmission electron microscopy, and western blotting analysis were used to extract and characterize exosomes. The effort of exosomal miR-1825 on endothelial cells was examined by transwell assay, wound healing assay, tube formation assay, and aortic ring assay. The relationship of miR-1825, ING1 and the downstream pathway were analyzed by western blot, RT-PCR, Immunofluorescence, and dual-luciferase reporter system analysis.ResultsExosomal miR-1825 is associated with angiogenesis in CRC and is enriched in exosomes extracted from the serum of CRC patients. The CRC-secreted exosomal miR-1825 can be transferred into vascular endothelial cells, promoting endothelial cell migration and tube formation in vitro, and facilitating angiogenesis and tumor metastasis in vivo. Mechanistically, exosomal miR-1825 regulates angiogenesis and tumor metastasis by suppressing inhibitor of growth family member 1 (ING1) and activating the TGF-β/Smad2/Smad3 signaling pathway in the recipient HUVECs.ConclusionsOur study demonstrated the CRC-secreted exosomal miR-1825 could be transferred to vascular endothelial cells, subsequently leads to the inhibition of ING1 and the activation of the TGF-β/Smad2/Smad3 signaling pathway, thereby promoting angiogenesis and liver metastasis in CRC. Exosomal miR-1825 is thus a potential diagnostic and therapeutic target for CRC patients.

Pancreatic resection for metachronous colorectal cancer metastases: a case series multicenter study.

Pancreas resection for metachronous colorectal cancer metastasis is episodic and the role of surgery in the management of these patients is still debated. We recruited seven patients from three different centres and analyzed 30-day morbidity and mortality, oncological outcomes at 6 and 12 months. There was no postoperative mortality. Complications occurred in two patients (28,6%). All patients completed at least a 12-months follow-up. At 6-month follow-up, only one patient had a recurrence. At 12-month follow-up, no patients died for disease recurrence and one more patient had a new recurrence. Our series supports the feasibility and safety of pancreas resection in metastatic colorectal cancer suggesting that radical resection may improve the patient's prognosis.

Low Rates of Intrapulmonary Local Recurrence After Laser Metastasectomy: A Single-Center Retrospective Cohort Study of Colorectal Cancer Metastases.

Objective: Colorectal pulmonary metastasis is the most common resected metastatic disease of the lung. Pulmonary metastasectomy (PM) for colorectal oligometastases is a well-established intervention with curative intent. Local recurrence at the resection site in the lung is a problem, with an impact on survival. The use of a 1320 nm neodymium:yttrium aluminum garnet (Nd:YAG) laser causes the vaporization and coagulation at the resection line and thereby increases safety margins around the nodule. We aimed to evaluate the local recurrence rate after laser-assisted pulmonary metastasectomy (LPM) for colorectal metastases. Methods: We conducted a retrospective analysis of 49 patients treated with laser-assisted pulmonary metastasectomy for 139 metastatic nodules from colorectal cancer from 2010 to 2018. All nodules were resected using Nd:YAG 1320 nm laser, aiming for a safety margin of five mm. The minimum follow-up time after PM was 24 months. Results: Local intrapulmonary recurrence developed at 7 of the 139 (5.0%) resection sites in 5 of the 49 patients (10.2%). Microscopically incomplete resection was a significant risk factor for recurrence (p = 0.023). Larger nodule size (>12 mm) negatively impacted local recurrence (p = 0.024). Nodules larger or equal to 12 mm in size also lowered the patients' probability of survival by 67.29% (HR: 0.3271, 95% CI: 0.1265-0.846, p = 0.018). Conclusions: The rate of local recurrence at the resection site after LPM for colorectal metastases is low. Complete resection is a positive predictor of survival without local recurrence. Microscopic complete resection with the addition of vaporization and coagulation at the resection margin seems to be sufficient to prevent local recurrence. However, larger nodules may require larger safety margins.

Multimodal deep learning: tumor and visceral fat impact on colorectal cancer occult peritoneal metastasis.

This study proposes a multimodal deep learning (DL) approach to investigate the impact of tumors and visceral fat on occult peritoneal metastasis in colorectal cancer (CRC) patients. We developed a DL model named Multi-scale Feature Fusion Network (MSFF-Net) based on ResNet18, which extracted features of tumors and visceral fat from the longest diameter tumor section and the third lumbar vertebra level (L3) in preoperative CT scans of CRC patients. Logistic regression analysis was applied to patients' clinical data that integrated with DL features. A random forest (RF) classifier was established to evaluate the MSFF-Net's performance on internal and external test sets and compare it with radiologists' performance. The model incorporating fat features outperformed the single tumor modality in the internal test set. Combining clinical information with DL provided the best diagnostic performance for predicting peritoneal metastasis in CRC patients. The AUCs were 0.941 (95% CI: [0.891, 0.986], p = 0.03) for the internal test set and 0.911 (95% CI: [0.857, 0.971], p = 0.013) for the external test set. CRC patients with peritoneal metastasis had a higher visceral adipose tissue index (VATI) compared to those without. Maximum tumor diameter and VATI were identified as independent prognostic factors for peritoneal metastasis. Grad-CAM decision regions corresponded with the independent prognostic factors identified by logistic regression analysis. The study confirms the network features of tumors and visceral fat significantly enhance predictive performance for peritoneal metastasis in CRC. Visceral fat is a meaningful imaging biomarker for peritoneal metastasis's early detection in CRC patients. Question Current research on predicting colorectal cancer with peritoneal metastasis mainly focuses on single-modality analysis, while studies based on multimodal imaging information are relatively scarce. Findings The Multi-scale Feature Fusion Network, constructed based on ResNet18, can utilize CT images of tumors and visceral fat to detect occult peritoneal metastasis in colorectal cancer. Clinical relevance This study identified independent prognostic factors for colorectal cancer peritoneal metastasis and combines them with tumor and visceral fat network features, aiding early diagnosis and accurate prognostic assessment.

Accelerated Endosomal Escape of Splice-Switching Oligonucleotides Enables Efficient Hepatic Splice Correction.

Splice-switching oligonucleotides (SSOs) can restore protein functionality in pathologies and are promising tools for manipulating the RNA-splicing machinery. Delivery vectors can considerably improve SSO functionality in vivo and allow dose reduction, thereby addressing the challenges of RNA-targeted therapeutics. Here, we report a biocompatible SSO nanocarrier, based on redox-responsive disulfide cross-linked low-molecular-weight linear polyethylenimine (cLPEI), for overcoming multiple biological barriers from subcellular compartments to en-route serum stability and finally in vivo delivery challenges. Intracellularly responsive cross-links of cLPEI significantly accelerated the endosomal escape and offered efficient SSO release to the cell's nucleus, thereby leading to high splice correction in vitro. In vivo performance of cLPEI-SSOs was investigated in a novel transgenic mouse model for splice correction, spatiotemporal tracking of SSO delivery in wild-type mice, and biodistribution in a colorectal cancer peritoneal metastasis model. A single intravenous application of 5 mg kg-1 cLPEI-SSOs induced splice correction in liver, lung, kidney, and bladder, giving functional protein, which was validated by RT-PCR. Near-infrared (NIR) fluorescence imaging and X-ray computed tomography revealed improved organ retention and reduced renal excretion of SSOs. NIR microscopy demonstrated the accumulation of SSOs in angiogenic tumors within the pancreas. Successful nuclear delivery of SSOs was observed in the hepatocytes. Thus, cLPEI nanocarriers resulted in highly efficient splice correction in vivo, highlighting the critical role of the enhanced SSO bioavailability.

Decoupling chemical and mechanical signaling in colorectal cancer cell migration

Colorectal cancer metastasis is governed by a variety of chemical and mechanical signaling that are largely influenced by cancer-associated fibroblasts (CAFs) in the tumor microenvironment. Here, we deconvolute the chemical from mechanical signaling in the case of the colon cancer cell line HCT-116 and CAFs. We examined three chemoattractants (CXCL12, TGF-β, and activin A) which allegedly are secreted by CAFs and induce HCT-116 cell migration. None of the chemoattractants tested resulted in enhanced migration of HCT-116 in a 2D transwell assay, at low cell density. Similarly, CAF-conditioned media also did not lead to enhanced HCT-116 migration, while CAFs co-cultured in the transwell assay did lead to increased HCT-116 migration. This result suggests that either high cell densities are required for chemotaxis, and/or a reciprocal two-way signaling network between CAFs and HCT-116 is necessary to induce chemotaxis. Surprisingly, we find that HCT-116 cells exhibit enhanced migration along the axis of mechanical stress in a 3D collagen matrix, at very high cell densities. This migration is independent of whether the strain is induced mechanically or by CAFs. By comparing purely mechanical and purely chemical migration to a 3D co-culture of CAFs and HCT-116 containing both chemical and mechanical cues, it is concluded that HCT-116 migration is dominated by mechanical signaling, while chemical cues are less influential.

Pharmacophore-based identification and in Silico characterization of microbial metabolites as potential modulators of Wnt signaling pathway in colorectal cancer therapy.

Aberrant activation of the Wnt/β-catenin signaling pathway, primarily driven by APC mutation and AXIN degradation via Tankyrase, contributes significantly to colorectal cancer (CRC) progression and metastasis. The accumulation of β-catenin, resulting from the dysregulated ubiquitination, underscores the need for alternative therapeutic strategies targeting Tankyrase and β-catenin. This present study explores microbial metabolites as a source of novel anti-cancer agents, leveraging their unique bioactivity and structural diversity, often exhibiting superior target specificity and lower toxicity than synthetic drugs. Through a computational drug discovery pipeline, a large library of 27641 microbial metabolites was initially screened based on multiple drug-likeliness criteria, resulting in the selection of 2527 compounds. Among the screened compounds, an integrated computational workflow comprising molecular docking, molecular dynamic simulations (MDS), MM/PBSA analysis, and Principal component analysis (PCA) identified Terreustoxin I (T1) as a potential Tankyrase inhibitor. In contrast, compound 10- phenyl-[12]-cytochalasin Z16 (B1) demonstrated a strong binding affinity within the β-catenin active site. Under physiological conditions, these lead compounds were evaluated for conformational stability, binding efficacy, and dynamic behavior. Additionally, ADMET profiling, physiochemical properties, and bioactivity score predictions confirmed the identified compounds' pharmacokinetic suitability and reduced toxicity profile. In silico, cytotoxicity predictions showed significant activity against SW480 and HCT90 colorectal cell lines, with additional anti-neoplastic and anti-leukemic properties, strengthening their candidacy as effective anti-cancer agents. These findings provide a foundation for further experimental validation and development of novel CRC therapies with improved safety and efficacy potential.

Hypointense Findings on Hepatobiliary Phase MR Images.

Hepatobiliary (HB) contrast agents are increasingly valuable diagnostic tools in MRI, offering a wider range of applications as their clinical use expands. Normal hepatocytes take up HB contrast agents, which are subsequently excreted in bile. This property creates a distinct HB phase providing valuable insights into liver function and biliary anatomy. HB contrast agents can assist in diagnosing a broad spectrum of HB diseases ranging from diffuse liver disease to focal hepatic lesions and can delineate anatomic details of the biliary tree. Understanding the pharmacodynamics of HB contrast agents is paramount to their appropriate clinical application and troubleshooting. HB phase hypointensity can arise from various diffuse and focal abnormalities that may or may not be associated with biliary excretion. Hypointensity during the HB phase can be broadly grouped into diffuse hypointensity, regional hypointensity, and focal lesions for better evaluation of the underlying cause. Abnormalities may arise from hepatic parenchymal, biliary, or vascular causes, or a combination thereof in each of the broad groups. Recognition of a suboptimal hypointense HB phase is important in the evaluation of focal lesions in patients with cirrhosis of the liver and particularly in those with hepatocellular carcinoma. Furthermore, hypointensity can also suggest the aggressiveness of malignancies such as hepatocellular carcinoma or colorectal metastases, which may affect the prognosis. It is essential to consider all imaging findings relative to the clinical context and the complete set of the MRI sequences performed for diagnosis of liver abnormalities. This comprehensive approach minimizes the risk of misinterpretation or pitfalls. The authors aim to equip radiologists with key insights for accurately understanding hypointensity in the HB phase, ultimately leading to more accurate diagnoses. ©RSNA, 2025 Supplemental material is available for this article.

A common malignancy in an uncommon site: colorectal adenocarcinoma metastasis to larynx

A common malignancy in an uncommon site: colorectal adenocarcinoma metastasis to larynx

Colorectal Pancreatic Metastases: A Three-Case Series and Literature Review.

Introduction: Pancreatic metastases are very rare tumors comprising 2-5 % of all malignant tumors of the pancreas. Colorectal pancreatic metastases are rare - 1.7%. Clinical features: Three patients with colo-rectal pancreatic metastasis were resected in our departament. The immunohsitochemical examination was positive for colorectal origin. Extensive imagistic work-up excluded extrapancreatic disease and allowed the surgical resection. Results: Three patients with personal history of colorectal cancer (2 - colon, 1 -rectal) were diagnosed with isolated pancreatic metastasis (2 in the head and one in body). Standard pancreatic resections were performed (2 pancreatico-duodenectomies and one distal spleno-pancreatectomy). One patient with associated vascular resection died postoperatively. The other two developed extrapancreatic recurrence and only one was resected (alive and disease free); the other died under systemic therapy. Conclusions: Surgical resection is recommended in selected patients, surgically fit, with resectable oligometastatic disease, in high-volume center with experience in pancreatic surgery.

Exploring the Role of Epithelial-Mesenchymal Transition During Colorectal Cancer Peritoneal Metastasis: Update on Their Mechanisms.

Colorectal cancer is a common malignant tumor worldwide. The prognosis of patients with colorectal cancer peritoneal metastasis is very poor. The study of the specific mechanisms of colorectal cancer peritoneal metastasis plays an important role in the treatment of patients with this disease. The mechanisms of colorectal cancer peritoneal metastasis are mainly pathological and biological. Biologically, the epithelial-mesenchymal transition process is an important precursor to tumor cell metastasis. Therefore, it is necessary to study the mechanisms of colorectal cancer peritoneal metastasis, especially the epithelial-mesenchymal transition, to identify new methods for the prevention and treatment of colorectal cancer peritoneal cancer, reduce the incidence of colorectal cancer peritoneal metastasis, and improve patient prognosis.

Crosstalk between GLTSCR1-deficient endothelial cells and tumour cells promotes colorectal cancer development by activating the Notch pathway.

Cancer stem cells (CSCs) typically reside in perivascular niches, but whether endothelial cells of blood vessels influence the stemness of cancer cells remains poorly understood. This study revealed that endothelial cell-specific GLTSCR1 deletion promotes colorectal cancer (CRC) tumorigenesis and metastasis by increasing cancer cell stemness. Mechanistically, knocking down GLTSCR1 induces the transformation of endothelial cells into tip cells by regulating the expression of Neuropilin-1 (NRP1), thereby increasing the direct contact and interaction between endothelial cells and tumour cells. In addition, GLTSCR1 inhibits JAG1 transcription by competing with acetylated p65(Lys-310) to bind to the BRD4 interaction site. Therefore, GLTSCR1 deficiency increases JAG1 expression in endothelial cells. Subsequently, increased JAG1 levels on tip cell membranes bind to Notch on CRC cell membranes, activating the Notch signalling pathway in tumour cells and increasing CRC cell stemness. Taken together, our findings highlight the roles of endothelial cells in CRC development.

ASO Author Reflections: Minimally Invasive Approach to Caudate Lobe Colorectal Metastasis with Inferior Vena Cava Involvement: Practical Technique for Caval Dissection and Handling.

ASO Author Reflections: Minimally Invasive Approach to Caudate Lobe Colorectal Metastasis with Inferior Vena Cava Involvement: Practical Technique for Caval Dissection and Handling.

PCDH17 induces colorectal cancer metastasis by destroying the vascular endothelial barrier

Compromised vascular integrity facilitates the cancer cells extravasation and metastasis. However, the mechanisms leading to a disruption in vascular integrity in colorectal cancer (CRC) remain unclear. In this study, PCDH17 expression was higher in the vascular endothelial cells of colon cancer with distant metastasis, and the rates of PCDH17+ endothelial cells (ECs) was associated with the M stage in clinical pathological characteristics analysis and correlated with a poor survival prognosis. The liver and lung metastatic dissemination of MC-38 was significantly decreased in PCDH17–/–mice. The ubiquitination and degradation of VEGFR2 was prevented by the interaction between PCDH17 and the E3 ubiquitin ligase MARCH5, which causing the separation of internalized VE-cadherin, and increased the vascular permeability and metastasis of CRC. These results highlight the importance of PCDH17 in maintaining vascular integrity, which has emphasis for endothelial barrier function in metastatic cancer. PCDH17 has the potential to be a marker for predicting tumor metastasis as well as a viable treatment target for CRC.