MRI in addition to CT in patients scheduled for local therapy of colorectal liver metastases (CAMINO): an international, multicentre, prospective, diagnostic accuracy trial.

BACKGROUND: Guidelines are inconclusive on whether contrast-enhanced MRI using gadoxetic acid and diffusion-weighted imaging should be added routinely to CT in the investigation of patients with colorectal liver metastases who are scheduled for curative liver resection or thermal ablation, or both. Although contrast-enhanced MRI is reportedly superior than contrast-enhanced CT in the detection and characterisation of colorectal liver metastases, its effect on clinical patient management is unknown. We aimed to assess the clinical effect of an additional liver contrast-enhanced MRI on local treatment plan in patients with colorectal liver metastases amenable to local treatment, based on contrast-enhanced CT. METHODS: We did an international, multicentre, prospective, incremental diagnostic accuracy trial in 14 liver surgery centres in the Netherlands, Belgium, Norway, and Italy. Participants were aged 18 years or older with histological proof of colorectal cancer, a WHO performance status score of 0-4, and primary or recurrent colorectal liver metastases, who were scheduled for local therapy based on contrast-enhanced CT. All patients had contrast-enhanced CT and liver contrast-enhanced MRI including diffusion-weighted imaging and gadoxetic acid as a contrast agent before undergoing local therapy. The primary outcome was change in the local clinical treatment plan (decided by the individual clinics) on the basis of liver contrast-enhanced MRI findings, analysed in the intention-to-image population. The minimal clinically important difference in the proportion of patients who would have change in their local treatment plan due to an additional liver contrast-enhanced MRI was 10%. This study is closed and registered in the Netherlands Trial Register, NL8039. FINDINGS: Between Dec 17, 2019, and July 31, 2021, 325 patients with colorectal liver metastases were assessed for eligibility. 298 patients were enrolled and included in the intention-to-treat population, including 177 males (59%) and 121 females (41%) with planned local therapy based on contrast-enhanced CT. A change in the local treatment plan based on liver contrast-enhanced MRI findings was observed in 92 (31%; 95% CI 26-36) of 298 patients. Changes were made for 40 patients (13%) requiring more extensive local therapy, 11 patients (4%) requiring less extensive local therapy, and 34 patients (11%) in whom the indication for curative-intent local therapy was revoked, including 26 patients (9%) with too extensive disease and eight patients (3%) with benign lesions on liver contrast-enhanced MRI (confirmed by a median follow-up of 21·0 months [IQR 17·5-24·0]). INTERPRETATION: Liver contrast-enhanced MRI should be considered in all patients scheduled for local treatment for colorectal liver metastases on the basis of contrast-enhanced CT imaging. FUNDING: The Dutch Cancer Society and Bayer AG - Pharmaceuticals.

A radiomics and genomics-derived model for predicting metastasis and prognosis in colorectal cancer.

Approximately 50% of colorectal cancer (CRC) patients would develop metastasis with poor prognosis, therefore, it is necessary to effectively predict metastasis in clinical treatment. In this study, we aimed to establish a machine-learning model for predicting metastasis in CRC patients by considering radiomics and transcriptomics simultaneously. Here, 1023 patients with CRC from three centers were collected and divided into five queues (Dazhou Central Hospital n = 517, Nanchong Central Hospital n = 120 and the Cancer Genome Atlas (TCGA) n = 386). A total of 854 radiomics features were extracted from tumor lesions on CT images, and 217 differentially expressed genes were obtained from non-metastasis and metastasis tumor tissues using RNA sequencing. Based on radiotranscriptomic (RT) analysis, a novel RT model was developed and verified through genetic algorithms (GA). Interleukin (IL)-26, a biomarker in RT model, was verified for its biological function in CRC metastasis. Furthermore, 15 radiomics variables were screened through stepwise regression, which was highly correlated with the IL26 expression level. Finally, a radiomics model (RA) was established by combining GA and stepwise regression analysis with radiomics features. The RA model exhibited favorable discriminatory ability and accuracy for metastasis prediction in two independent verification cohorts. We designed multicenter, multi-scale cohorts to construct and verify novel combined radiomics and genomics models for predicting metastasis in CRC. Overall, RT model and RA model might help clinicians in directing personalized diagnosis and therapeutic regimen selection for patients with CRC.

An Evaluation of Critical Factors for the Cost-Effectiveness of Real-Time Computer-Aided Detection: Sensitivity and Threshold Analyses Using a Microsimulation Model.

BACKGROUND & AIMS: The use of computer-aided detection (CAD) increases the adenoma detection rates (ADRs) during colorectal cancer (CRC) screening/surveillance. This study aimed to evaluate the requirements for CAD to be cost-effective and the impact of CAD on adenoma detection by endoscopists with different ADRs. METHODS: We developed a semi-Markov microsimulation model to compare the effectiveness of traditional colonoscopy (mean ADR, 26%) to colonoscopy with CAD (mean ADR, 37%). CAD was modeled as having a $75 per-procedure cost. Extensive 1-way sensitivity and threshold analysis were performed to vary cost and ADR of CAD. Multiple scenarios evaluated the potential effect of CAD on endoscopists' ADRs. Outcome measures were reported in incremental cost-effectiveness ratios, with a willingness-to-pay threshold of $100,000/quality-adjusted life year. RESULTS: When modeling CAD improved ADR for all endoscopists, the CAD cohort had 79 and 34 fewer lifetime CRC cases and deaths, respectively, per 10,000 persons. This scenario was dominant with a cost savings of $143 and incremental effectiveness of 0.01 quality-adjusted life years. Threshold analysis demonstrated that CAD would be cost-effective up to an additional cost of $579 per colonoscopy, or if it increases ADR from 26% to at least 30%. CAD reduced CRC incidence and mortality when limited to improving ADRs for low-ADR endoscopists (ADR <25%), with 67 fewer CRC cases and 28 CRC deaths per 10,000 persons compared with traditional colonoscopy. CONCLUSIONS: As CAD is implemented clinically, it needs to improve mean ADR from 26% to at least 30% or cost less than $579 per colonoscopy to be cost-effective when compared with traditional colonoscopy. Further studies are needed to understand the impact of CAD when used in community practice.

Novel Near-Infrared Fluorescent Probe for Hepatocyte Growth Factor in Vivo Imaging in Surgical Navigation of Colorectal Cancer.

Despite recent advancements in colorectal cancer (CRC) treatment, the prognosis remains unfavorable primarily due to high recurrence and liver metastasis rates. Fluorescence molecular imaging technologies, combined with specific probes, have gained prominence in facilitating real-time tumor resection guided by fluorescence. Hepatocyte growth factor (HGF) is overexpressed in CRC, but the advancement of HGF fluorescent probes has been impeded by the absence of effective HGF-targeting small-molecular ligands. Herein, we present the targeted capabilities of the novel V-1-GGGK-MPA probe labeled with a near-infrared fluorescent dye, which targets HGF in CRC. The V-1-GGGK peptide exhibits high specificity and selectivity for HGF-positive in vitro tumor cells and in vivo tumors. Biodistribution analysis of V-1-GGGK-MPA revealed tumor-specific accumulation with low background uptake, yielding signal-to-noise ratio (SNR) values of tumor-to-colorectal >6 in multiple subcutaneous CRC models 12 h postinjection. Quantitative analysis confirmed the probe's high uptake in SW480 and HT29 orthotopic and liver metastatic models, with SNR values of tumor-to-colorectal and -liver being 5.6 ± 0.4, 4.6 ± 0.5, and 2.1 ± 0.3, 2.0 ± 0.5, respectively, enabling precise tumor visualization for surgical navigation. Pathological analysis demonstrated the excellent tumor boundaries discrimination capacity of the V-1-GGGK-MPA probe at the molecular level. With its rapid tumor targeting, sustained tumor retention, and precise tumor boundary delineation, V-1-GGGK-MPA merges as a promising HGF imaging agent, enriching the toolbox of intraoperative navigational fluorescent probes for CRC.

Evaluation of the tumor-targeting specific imaging and killing effect of a CEA-targeting nanoparticle in colorectal cancer.

INTRODUCTION: Colorectal cancer (CRC) is a prevalent digestive malignancy with significant global mortality and morbidity rates. Improving diagnostic capabilities for CRC and investigating novel therapeutic approaches are pressing clinical imperatives. Additionally, carcinoembryonic antigen (CEA) has emerged as a highly promising candidate for both colorectal tumor imaging and treatment. METHODS: A novel active CEA-targeting nanoparticle, CEA(Ab)-MSNs-ICG-Pt, was designed and synthesized, which served as a tumor-specific fluorescence agent to help in CRC near-infrared (NIR) fluorescence imaging. In cell studies, CEA(Ab)-MSNs-ICG-Pt exhibited specific targeting to RKO cells through specific antibody-antigen binding of CEA, resulting in distribution both within and around these cells. The tumor-targeting-specific imaging capabilities of the nanoparticle were determined through in vivo fluorescence imaging experiments. Furthermore, the efficacy of the nanoparticle in delivering chemotherapeutics and its killing effect were evaluated both in vitro and in vivo. RESULTS: The CEA(Ab)-MSNs-ICG-Pt nanoparticle, designed as a novel targeting agent for carcinoembryonic antigen (CEA), exhibited dual functionality as a targeting fluorescent agent. This CEA-targeting nanoparticle showed exceptional efficacy in eradicating CRC cells in comparison to individual treatment modalities. Furthermore, it exhibits exceptional biosafety and biocompatibility properties. CEA(Ab)-MSNs-ICG-Pt exhibits significant promise due to its ability to selectively target tumors through NIR fluorescence imaging and effectively eradicate CRC cells with minimal adverse effects in both laboratory and in vivo environments. CONCLUSION: The favorable characteristics of CEA(Ab)-MSNs-ICG-Pt offer opportunities for its application in chemotherapeutic interventions, tumor-specific NIR fluorescence imaging, and fluorescence-guided surgical procedures.

BATF promotes tumor progression and association with FDG PET-derived parameters in colorectal cancer.

PURPOSE: The purpose of the study was to evaluate the expression and function of basic leucine zipper ATF-like transcription factor (BATF) in colorectal cancer (CRC), and its correlation with 2-deoxy-2[18F]fluoro-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) parameters. METHODS: The TIMER database, GEPIA database, TCGA, and GEO database were used to analyze the expression profile of BATF in human cancers. The reverse transcription­quantitative PCR and western blot analyses were used to evaluate the mRNA level and protein expression in different CRC cell lines. The expression of BATF in SW620 and HCT116 cells was silenced and cell counting kit-8 assays and clonogenic assay were utilized to evaluate the role of BATF in CRC proliferation. The expression of tumor BATF and glucose transporter 1 (GLUT-1) were examined using immunohistochemical tools in 37 CRC patients undergoing preoperative 18F-FDG PET/CT imaging. The correlation between the PET/CT parameters and immunohistochemical result was evaluated. RESULTS: In database, BATF was highly expressed in pan-cancer analyses, including CRC, and was associated with poor prognosis in CRC. In vitro, the results showed that knocking down of BATF expression could inhibit the proliferation of SW620 and HCT116 cells. In CRC patients, BATF expression was upregulated in tumor tissues compared with matched para-tumoral tissues, and was related with gender and Ki-67 levels. BATF expression was positively related to GLUT-1 expression and PET/CT parameters, including tumor size, maximum standard uptake value, metabolic tumor volume, and total lesion glycolysis. The multiple logistic analyses showed that SUVmax was an independent predictor of BATF expression. With 15.96 g/cm3 as the cutoff, sensitivity was 85.71%, specificity 82.61%, and area-under-the-curve 0.854. CONCLUSION: BATF may be an oncogene associated with 18F-FDG PET/CT parameters in CRC. SUVmax may be an independent predictor of BATF expression.

STING-targeted PET tracer for early assessment of tumor immunogenicity in colorectal cancer after chemotherapy.

PURPOSE: To optimize chemotherapy regimens and improve the effectiveness of chemotherapy combined with immunotherapy, a PET tracer specifically targeting the stimulator of interferon genes (STING), denoted as [18F]FBTA was used to monitor the early changes in tumor immunogenicity after chemotherapy in colorectal cancer (CRC) mice. METHODS: The toluene sulfonate precursor was labeled with 18F to produce the STING targeted probe-[18F]FBTA. [18F]FBTA-PET imaging and biodistribution were performed using CRC mice treated with oxaliplatin (OXA) or cisplatin (CDDP). CRC mice were also treated with low (CDDP-LD: 1 mg/kg) or medium (CDDP-MD: 2.5 mg/kg) doses of CDDP, and subjected to PET imaging and biodistribution. The effects of different chemotherapeutic agents and different doses of CDDP on tumor innate immunity were verified by flow cytometry and immunohistochemistry. RESULTS: PET imaging of CRC mice exhibited notably enhanced tumor uptake in the early phase of chemotherapy with treatment with OXA (3.09 ± 0.25%ID/g) and CDDP (4.01 ± 0.18%ID/g), especially in the CDDP group. The PET-derived tumor uptake values have strong correlations with STING immunohistochemical score. Flow cytometry showed both agents led to DCs and macrophages infiltration in tumors. Compared with OXA, CDDP treatment recruits more DCs and macrophages in CRC tumors. Both CDDP-LD and CDDP-MD treatment elevated uptake in CRC tumors, especially in CDDP-MD group. Immunohistochemistry and flow cytometry confirmed CDDP-MD treatment recruits more DCs and macrophages than CDDP-LD treatment. CONCLUSION: Overall, the STING-targeted tracer-[18F]FBTA was demonstrated to monitor early changes in tumor immunogenicity in CRC mice after chemotherapy. Besides, the STING-targeted strategy may help to select the appropriate chemotherapy regimen, including chemotherapeutic agents and doses, which further improve clinical decision making for combination immunotherapy after chemotherapy for CRC.

2-[18F]FDG PET-based quantification of lymph node metabolic heterogeneity for predicting lymph node metastasis in patients with colorectal cancer.

BACKGROUND AND PURPOSE: The pre-surgical estimation of lymph node (LN) metastasis in colorectal cancer (CRC) poses a significant diagnostic predicament. The associations between LN morphology, density, and metabolic heterogeneity and LN metastasis status in CRCs have been seldomly examined through the lens of radiomics. This research aimed to assess 2-[18F]FDG PET-based quantification of intratumoral metabolic heterogeneity for predicting lymph node metastasis in patients with colorectal cancer. MATERIALS AND METHODS: The construction of the model utilized data from 264 CRC patients, all of whom underwent preoperative 2-[18F]FDG PET/CT. Radiomic features were extracted from PET and CT images of LNs. Least absolute shrinkage and selection operator (LASSO) regression was implemented for selecting pertinent imaging features with a tenfold cross-validation. The predictive accuracy for LN metastasis status was juxtaposed against traditional methodologies (comprising CT-reported LN status and PET/CT-reported LN status) by deploying the receiver operating characteristic (ROC) curve analysis. The radiomics signature was evaluated based on discrimination, calibration, and clinical utility parameters. The model was further subjected to validation using an independent cohort of 132 patients from the period of January 2012 to June 2020. RESULTS: The radiomics model was composed of eight significant radiomic features (five from PET and three from CT), encapsulating metabolic and density heterogeneity. The radiomics signature (area under the curve (AUC), 0.908) showcased a significantly superior performance compared to CT-reported LN status (AUC, 0.563, P < 0.001) and PET/CT-reported LN status (AUC, 0.64, P < 0.001) for predicting LN-positive or LN-negative status. The radiomics signature (AUC, 0.885) also showcased a significantly superior performance compared to CT-reported LN status (AUC, 0.587, P < 0.001) and PET/CT-reported LN status (AUC, 0.621, P < 0.001) to identify N1 and N2. This signature maintained its independence from clinical risk factors and exhibited robustness in the validation test set. Decision curve analysis attested to the clinical utility of the radiomics signature. CONCLUSIONS: The radiomics signature based on 2-[18F]FDG PET/CT, which derived image features directly from LNs irrespective of clinical risk factors, displayed enhanced diagnostic performance compared to conventional CT or PET/CT-reported LN status. This allows for the identification of pre-surgical LN metastasis status and facilitates a patient-specific prediction of LN metastasis status in CRC patients.

Use of 3D-CT-derived psoas major muscle volume in defining sarcopenia in colorectal cancer.

BACKGROUND: Sarcopenia is characterized by reduced skeletal muscle volume and is a condition that is prevalent among elderly patients and associated with poor prognosis as a comorbidity in malignancies. Given the aging population over 80 years old in Japan, an understanding of malignancies, including colorectal cancer (CRC), complicated by sarcopenia is increasingly important. Therefore, the focus of this study is on a novel and practical diagnostic approach of assessment of psoas major muscle volume (PV) using 3-dimensional computed tomography (3D-CT) in diagnosis of sarcopenia in patients with CRC. METHODS: The subjects were 150 patients aged ≥ 80 years with CRC who underwent primary tumor resection at Juntendo University Hospital between 2004 and 2017. 3D-CT measurement of PV and conventional CT measurement of the psoas major muscle cross-sectional area (PA) were used to identify sarcopenia (group S) and non-sarcopenia (group nS) cases. Clinicopathological characteristics, operative results, postoperative complications, and prognosis were compared between these groups. RESULTS: The S:nS ratios were 15:135 for the PV method and 52:98 for the PA method. There was a strong positive correlation (r = 0.66, p < 0.01) between PVI (psoas major muscle volume index) and PAI (psoas major muscle cross-sectional area index), which were calculated by dividing PV or PA by the square of height. Surgical results and postoperative complications did not differ significantly in the S and nS groups defined using each method. Overall survival was worse in group S compared to group nS identified by PV (p < 0.01), but not significantly different in groups S and nS identified by PA (p = 0.77). A Cox proportional hazards model for OS identified group S by PV as an independent predictor of a poor prognosis (p < 0.05), whereas group S by PA was not a predictor of prognosis (p = 0.60). CONCLUSIONS: The PV method for identifying sarcopenia in elderly patients with CRC is more practical and sensitive for prediction of a poor prognosis compared to the conventional method.

Prospective study of diagnostic yields of flexible spectral imaging color enhancement installed in colon capsule endoscopy for colorectal polyps and tumors.

BACKGROUND AND AIMS: We prospectively determined the efficacy of flexible spectral imaging color enhancement (FICE) used with second-generation colon capsule endoscopy (CCE) for colorectal polyps and tumors (CRTs). METHODS: This study included optical colonoscopy within 4 months after CCE. Two colonoscopists independently reviewed CCE using white-light images (CCE-WL) and CCE using FICE images (CCE-FICE), respectively. Based on colonoscopic findings as the criterion standard, the diagnostic accuracy for CRTs was compared between CCE-WL and CCE-FICE. RESULTS: Of 89 enrolled patients (65 men and 24 women; 75 with CRTs including 36 with serrated lesions, 63 with adenomas, and 9 with adenocarcinomas), the per-patient detectability of CCE-FICE for the representative CRTs was significantly higher than that of CCE-WL: overall CRTs (CCE-WL, 79%; CCE-FICE, 88%; P = .0001), 6- to 9-mm CRTs (CCE-WL, 63%; CCE-FICE, 94%; P = .0055), and ≥6-mm CRTs (CCE-WL, 78%; CCE-FICE, 93%; P = .0159). The per-lesion sensitivity of CCE-FICE was significantly higher than that of CCE-WL for CRTs: overall (CCE-WL, 61%; CCE-FICE, 79%; P < .0001), <6 mm (CCE-WL, 53%; CCE-FICE, 69%; P < .0001), 6- to 9-mm CRTs (CCE-WL, 65%; CCE-FICE, 93%; P = .0007), slightly elevated CRTs (CCE-WL, 53%; CCE-FICE, 75%; P < .0001), tubular adenomas (CCE-WL, 61%; CCE-FICE, 79%; P < .0001), and serrated polyps (CCE-WL, 57%; CCE-FICE, 74%; P = .0022). Both modes detected all adenocarcinomas. No significant differences were found between CCE-WL and CCE-FICE of the per-lesion sensitivity for ≥10-mm CRTs (CCE-WL, 81%; CCE-FICE, 94%; P = .1138) or protruding CRTs (CCE-WL, 77%; CCE-FICE, 86%; P = .0614). Kappa coefficients for overall CRTs for CCE-WL and CCE-FICE were .66 and .64, respectively, which indicated substantial agreement. CONCLUSIONS: CCE-FICE improved the detection rates for all CRTs except adenocarcinomas, ≥10-mm polyps, and protruding polyps when compared with CCE-WL. (Clinical trial registration number: UMIN 000021125.).

A real-time deep learning-based system for colorectal polyp size estimation by white-light endoscopy: development and multicenter prospective validation.

BACKGROUND: The choice of polypectomy device and surveillance intervals for colorectal polyps are primarily decided by polyp size. We developed a deep learning-based system (ENDOANGEL-CPS) to estimate colorectal polyp size in real time. METHODS: ENDOANGEL-CPS calculates polyp size by estimating the distance from the endoscope lens to the polyp using the parameters of the lens. The depth estimator network was developed on 7297 images from five virtually produced colon videos and tested on 730 images from seven virtual colon videos. The performance of the system was first evaluated in nine videos of a simulated colon with polyps attached, then tested in 157 real-world prospective videos from three hospitals, with the outcomes compared with that of nine endoscopists over 69 videos. Inappropriate surveillance recommendations caused by incorrect estimation of polyp size were also analyzed. RESULTS: The relative error of depth estimation was 11.3% (SD 6.0%) in successive virtual colon images. The concordance correlation coefficients (CCCs) between system estimation and ground truth were 0.89 and 0.93 in images of a simulated colon and multicenter videos of 157 polyps. The mean CCC of ENDOANGEL-CPS surpassed all endoscopists (0.89 vs. 0.41 [SD 0.29]; P<0.001). The relative accuracy of ENDOANGEL-CPS was significantly higher than that of endoscopists (89.9% vs. 54.7%; P<0.001). Regarding inappropriate surveillance recommendations, the system's error rate is also lower than that of endoscopists (1.5% vs. 16.6%; P<0.001). CONCLUSIONS: ENDOANGEL-CPS could potentially improve the accuracy of colorectal polyp size measurements and size-based surveillance intervals.

Linked-color imaging with or without artificial intelligence for adenoma detection: a randomized trial.

BACKGROUND: Adenoma detection rate (ADR) is an important indicator of colonoscopy quality and colorectal cancer incidence. Both linked-color imaging (LCI) with artificial intelligence (LCA) and LCI alone increase adenoma detection during colonoscopy, although it remains unclear whether one modality is superior. This study compared ADR between LCA and LCI alone, including according to endoscopists' experience (experts and trainees) and polyp size. METHODS: Patients undergoing colonoscopy for positive fecal immunochemical tests, follow-up of colon polyps, and abdominal symptoms at a single institution were randomly assigned to the LCA or LCI group. ADR, adenoma per colonoscopy (APC), cecal intubation time, withdrawal time, number of adenomas per location, and adenoma size were compared. RESULTS: The LCA (n=400) and LCI (n=400) groups showed comparable cecal intubation and withdrawal times. The LCA group showed a significantly higher ADR (58.8% vs. 43.5%; P<0.001) and mean (95%CI) APC (1.31 [1.15 to 1.47] vs. 0.94 [0.80 to 1.07]; P<0.001), particularly in the ascending colon (0.30 [0.24 to 0.36] vs. 0.20 [0.15 to 0.25]; P=0.02). Total number of nonpolypoid-type adenomas was also significantly higher in the LCA group (0.15 [0.09 to 0.20] vs. 0.08 [0.05 to 0.10]; P=0.02). Small polyps (≤5, 6-9mm) were detected significantly more frequently in the LCA group (0.75 [0.64 to 0.86] vs. 0.48 [0.40 to 0.57], P<0.001 and 0.34 [0.26 to 0.41] vs. 0.24 [0.18 to 0.29], P=0.04, respectively). In both groups, ADR was not significantly different between experts and trainees. CONCLUSIONS: LCA was significantly superior to LCI alone in terms of ADR.

Application of clustering strategy for automatic segmentation of tissue regions in mass spectrometry imaging.

RATIONALE: Mass spectrometry imaging (MSI) has been widely used in biomedical research fields. Each pixel in MSI consists of a mass spectrum that reflects the molecule feature of the tissue spot. Because MSI contains high-dimensional datasets, it is highly desired to develop computational methods for data mining and constructing tissue segmentation maps. METHODS: To visualize different tissue regions based on mass spectrum features and improve the efficiency in processing enormous data, we proposed a computational strategy that consists of four procedures including preprocessing, data reduction, clustering, and quantitative validation. RESULTS: In this study, we examined the combination of t-distributed stochastic neighbor embedding (t-SNE) and hierarchical clustering (HC) for MSI data analysis. Using publicly available MSI datasets, one dataset of mouse urinary bladder, and one dataset of human colorectal cancer, we demonstrated that the generated tissue segmentation maps from this combination were superior to other data reduction and clustering algorithms. Using the staining image as a reference, we assessed the performance of clustering algorithms with external and internal clustering validation measures, including purity, adjusted Rand index (ARI), Davies-Bouldin index (DBI), and spatial aggregation index (SAI). The result indicated that SAI delivered excellent performance for automatic segmentation of tissue regions in MSI. CONCLUSIONS: We used a clustering algorithm to construct tissue automatic segmentation in MSI datasets. The performance was evaluated by comparing it with the stained image and calculating clustering validation indexes. The results indicated that SAI is important for automatic tissue segmentation in MSI, different from traditional clustering validation measures. Compared to the reports that used internal clustering validation measures such as DBI, our method offers more effective evaluation of clustering results for MSI segmentation. We envision that the proposed automatic image segmentation strategy can facilitate deep learning in molecular feature extraction and biomarker discovery for the biomedical applications of MSI.

Predictive value of 18F-fluorodeoxyglucose PET/CT in histological grade of incidental colorectal adenoma.

BACKGROUND: 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/computed tomography (PET/CT) as an imaging modality for the whole body has shown its value in detecting incidental colorectal adenoma. In clinical practice, adenomatous polyps can be divided into three groups: low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN) and cancer, which can lead to different clinical management. However, the relationship between the 18F-FDG PET/CT SUVmax and the histological grade of adenomatous polyps is still not established, which is a challenging but valuable task. METHODS: This retrospective study included 255 patients with colorectal adenoma (CRA) or colorectal adenocarcinomas (AC) who had corresponding 18F-FDG uptake incidentally found on PET/CT. The correlations of SUVmax with pathological characteristics and tumor size were assessed. Neoplasms were divided into LGIN, HGIN, and AC according to histological grade. Receiver operating characteristic (ROC) analysis was applied to evaluate the predictive value of the SUVmax-only model and comprehensive models which were established with imaging and clinical predictors identified by univariate and multivariate analysis. RESULTS: The SUVmax was positively correlated with histological grades (r=0.529, P<0.001). Univariate and multivariate analysis showed that SUVmax was an independent risk factor among all groups except between HGIN and AC. The area under the curves (AUCs) of the comprehensive model for distinguishing between AC and adenoma, LGIN and HIGN, LGIN and AC, and HGIN and AC were 0.886, 0.780, 0.945, 0.733, respectively, which is statistically higher than the AUCs of the SUVmax-only model with 0.812, 0.733, 0.863, and 0.688, respectively. CONCLUSIONS: As an independent risk factor, SUVmax based on 18F-FDG PET/CT is highly associated with the histological grade of CRA. Thus, 18F-FDG PET/CT can serve as a noninvasive tool for precise diagnosis and assist in the preoperative formulation of treatment strategies for patients with incidental CRA.

Sociodemographic Factors and Screening CT Colonography Use Among Medicare Beneficiaries.

BACKGROUND. Approximately one-third of the eligible U.S. population have not undergone guideline-compliant colorectal cancer (CRC) screening. Guidelines recognize various screening strategies to increase adherence. CMS provides coverage for all recommended screening tests except CT colonography (CTC). OBJECTIVE. The purpose of this study was to compare CTC and other CRC screening tests in terms of associations of utilization with income, race and ethnicity, and urbanicity in Medicare fee-for-service beneficiaries. METHODS. This retrospective study used CMS Research Identifiable Files from January 1, 2011, through December 31, 2020. These files contain claims information for 5% of Medicare fee-for-service beneficiaries. Data were extracted for individuals 45-85 years old, and individuals with high CRC risk were excluded. Multivariable logistic regression models were constructed to determine the likelihood of undergoing CRC screening tests (as well as of undergoing diagnostic CTC, a CMS-covered test with similar physical access as screening CTC) as a function of income, race and ethnicity, and urbanicity while controlling for sex, age, Charlson comorbidity index, U.S. census region, screening year, and related conditions and procedures. RESULTS. For 12,273,363 beneficiary years (mean age, 70.5 ± 8.2 [SD] years; 2,436,849 unique beneficiaries: 6,774,837 female beneficiaries, 5,498,526 male beneficiaries), there were 785,103 CRC screenings events, including 645 for screening CTC. Compared with individuals living in communities with per capita income of less than US$25,000, individuals in communities with income of US$100,000 or more had OR for undergoing screening CTC of 5.73, optical colonoscopy (OC) of 1.36, sigmoidoscopy of 1.03, guaiac fecal occult blood test or fecal immunochemical test of 1.50, stool DNA of 1.43, and diagnostic CTC of 2.00. The OR for undergoing screening CTC was 1.00 for Hispanic individuals and 1.08 for non-Hispanic Black individuals compared with non-Hispanic White individuals. Compared with the OR for undergoing screening CTC for residents of metropolitan areas, the OR was 0.51 for residents of micropolitan areas and 0.65 for residents of small or rural areas. CONCLUSION. The association with income was substantially larger for screening CTC than for other CRC screening tests or for diagnostic CTC. CLINICAL IMPACT. Medicare's noncoverage for screening CTC may contribute to lower adherence with CRC screening guidelines for lower-income beneficiaries. Medicare coverage of CTC could reduce income-based disparities for individuals avoiding OC owing to invasiveness, need for anesthesia, or complication risk.

Predictive value of preoperative CT enhancement rate and CT perfusion parameters in colorectal cancer.

BACKGROUND: Angiogenesis is a critical step in colorectal cancer growth, progression and metastasization. CT are routine imaging examinations for preoperative clinical evaluation in colorectal cancer patients. This study aimed to investigate the predictive value of preoperative CT enhancement rate (CER) and CT perfusion parameters on angiogenesis in colorectal cancer, as well as the association of preoperative CER and CT perfusion parameters with serum markers. METHODS: This retrospective analysis included 42 patients with colorectal adenocarcinoma. Median of microvessel density (MVD) as the cut-off value, it divided 42 patients into high-density group (MVD ≥ 35/field, n = 24) and low-density group (MVD < 35/field, n = 18), and 25 patients with benign colorectal lesions were collected as the control group. Statistical analysis of CER, CT perfusion parameters, serum markers were performed in all groups. Receiver operating curves (ROC) were plotted to evaluate the diagnostic efficacy of relevant CT perfusion parameters for tumor angiogenesis; Pearson correlation analysis explored potential association between CER, CT perfusion parameters and serum markers. RESULTS: CER, blood volume (BV), blood flow (BF), permeability surface (PS) and carbohydrate antigen 19 - 9 (CA19-9), carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), trefoil factor 3 (TFF3), vascular endothelial growth factor (VEGF) in colorectal adenocarcinoma were significantly higher than those in the control group, the parameters in high-density group were significantly higher than those in the low-density group (P < 0.05); however, the time to peak (TTP) of patients in colorectal adenocarcinoma were significantly lower than those in the control group, and the high-density group showed a significantly lower level compared to the low-density group (P < 0.05). The combined parameters BF + TTP + PS and BV + BF + TTP + PS demonstrated the highest area under the curve (AUC), both at 0.991. Pearson correlation analysis showed that the serum levels of CA19-9, CA125, CEA, TFF3, and VEGF in patients showed positive correlations with CER, BV, BF, and PS (P < 0.05), while these indicators exhibited negative correlations with TTP (P < 0.05). CONCLUSIONS: Some single and joint preoperative CT perfusion parameters can accurately predict tumor angiogenesis in colorectal adenocarcinoma. Preoperative CER and CT perfusion parameters have certain association with serum markers.

Prediction of lymph node metastasis in T1 colorectal cancer based on combination of body composition and vascular invasion.

OBJECTIVES: Lymph node metastasis (LNM) in colorectal cancer (CRC) patients is not only associated with the tumor's local pathological characteristics but also with systemic factors. This study aims to assess the feasibility of using body composition and pathological features to predict LNM in early stage colorectal cancer (eCRC) patients. METHODS: A total of 192 patients with T1 CRC who underwent CT scans and surgical resection were retrospectively included in the study. The cross-sectional areas of skeletal muscle, subcutaneous fat, and visceral fat at the L3 vertebral body level in CT scans were measured using Image J software. Logistic regression analysis were conducted to identify the risk factors for LNM. The predictive accuracy and discriminative ability of the indicators were evaluated using receiver operating characteristic (ROC) curves. Delong test was applied to compare area under different ROC curves. RESULTS: LNM was observed in 32 out of 192 (16.7%) patients with eCRC. Multivariate analysis revealed that the ratio of skeletal muscle area to visceral fat area (SMA/VFA) (OR = 0.021, p = 0.007) and pathological indicators of vascular invasion (OR = 4.074, p = 0.020) were independent risk factors for LNM in eCRC patients. The AUROC for SMA/VFA was determined to be 0.740 (p < 0.001), while for vascular invasion, it was 0.641 (p = 0.012). Integrating both factors into a proposed predictive model resulted in an AUROC of 0.789 (p < 0.001), indicating a substantial improvement in predictive performance compared to relying on a single pathological indicator. CONCLUSION: The combination of the SMA/VFA ratio and vascular invasion provides better prediction of LNM in eCRC.

Whole-body MRI with diffusion-weighted imaging as an adjunct to18 F-fluorodeoxyglucose positron emission tomography and CT in patients with suspected recurrent colorectal cancer.

AIM: The aim was to explore how findings of whole-body MRI including diffusion-weighted imaging (DW-MRI) compared to the routine diagnostic workup with CT and/or 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in patients with suspected recurrent colorectal cancer (CRC). METHOD: This was an exploratory retrospective analysis of 55 patients with a clinical suspicion of recurrent CRC who underwent DW-MRI following CT and/or FDG-PET/CT. Two readers in consensus interpreted all clinical imaging reports and converted each described lesion into a confidence score (1 = definitely benign to 5 = definitely malignant). DW-MRI findings were compared to the most recent previous CT or PET/CT. Any discrepant or additional DW-MRI findings were documented and compared with histology and/or clinical follow-up (if available). RESULTS: Whole-body MRI including diffusion-weighted imaging (DW-MRI) resulted in discrepant/additional findings in 26/55 (47%) cases; 23/37 (62%) compared to previous CT and 3/18 (17%) compared to previous PET/CT. These included 10 cases where DW-MRI converted previously inconclusive CT (n = 8) or PET/CT (n = 2) findings into a conclusive diagnosis, one where it contradicted a previous CT diagnosis of recurrence, five where DW-MRI diagnosed recurrent disease not previously reported on CT and 10 cases where DW-MRI detected additional lesions compared to CT (n = 9) or PET/CT (n = 1). Eighty-eight per cent of cases with discrepant/additional findings concerned patients with recurrent/metachronous peritoneal metastases. In total, DW-MRI resulted in 42 discrepant/additional lesions; the DW-MRI diagnosis was correct in 76% of these lesions and incorrect (false positive) in 7%. In the remaining 17%, no standard of reference was available. CONCLUSIONS: This explorative study suggests that DW-MRI may be of added value to patients with a clinical suspicion for recurrent CRC, in particular to identify patients with peritoneal metastases. DW-MRI mainly has potential as a 'problem-solver' in patients with inconclusive or negative findings on previous imaging (in particular CT) and to detect additional disease sites in patients already diagnosed with recurrent disease.

Impact of standardising indocyanine green fluorescence angiography technique for visual and quantitative interpretation on interuser variability in colorectal surgery.

AIM/BACKGROUND: Intra-operative colonic perfusion assessment via indocyanine green fluorescence angiography (ICGFA) aims to address malperfusion-related anastomotic complications; however, its interpretation suffers interuser variability (IUV), especially early in ICGFA experience. This work assesses the impact of a protocol developed for both operator-based judgement and computational development on interpretation consistency, focusing on senior surgeons yet to start using ICGFA. METHODS: Experienced and junior gastrointestinal surgeons were invited to complete an ICGFA-experience questionnaire. They subsequently interpreted nine operative ICGFA videos regarding perfusion sufficiency of a surgically prepared distal colon during laparoscopic anterior resection by indicating their preferred site of proximal transection using an online annotation platform (mindstamp.com). Six ICGFA videos had been prepared with a clinical standardisation protocol controlling camera and patient positioning of which three each had monochrome near infrared (NIR) and overlay display. Three others were non-standardised controls with synchronous NIR and overlay picture-in-picture display. Differences in transection level between different cohorts were assessed for intraclass correlation coefficient (ICC) via ImageJ and IBM SPSS. RESULTS: 58 clinicians (12 ICGFA experts, 46 ICGFA inexperienced of whom 23 were either finished or within one year of finishing training and 23 were junior trainees) participated as per power calculations. 63% felt that ICGFA should be routinely deployed with 57% believing interpretative competence requires 11-50 cases. Transection level concordance was generally good (ICC = 0.869) across all videos and levels of expertise (0.833-0.915). However, poor agreement was evident with the standardised protocol videos for overlay presentation (0.208-0.345). Similarly, poor agreement was seen for the monochrome display (0.392-0.517), except for those who were trained but ICG inexperienced (0.877) although even here agreement was less than with unstandardised videos (0.943). CONCLUSION: Colorectal ICGFA acquisition and display standardisation impacts IUV with this specific protocol tending to diminish surgeon interpretation consistency. ICGFA video recording for computational development may require dedicated protocols.

Preoperative MRI radiomic analysis for predicting local tumor progression in colorectal liver metastases before microwave ablation.

PURPOSE: Radiomics may aid in predicting prognosis in patients with colorectal liver metastases (CLM). Consistent data is available on CT, yet limited data is available on MRI. This study assesses the capability of MRI-derived radiomic features (RFs) to predict local tumor progression-free survival (LTPFS) in patients with CLMs treated with microwave ablation (MWA). METHODS: All CLM patients with pre-operative Gadoxetic acid-MRI treated with MWA in a single institution between September 2015 and February 2022 were evaluated. Pre-procedural information was retrieved retrospectively. Two observers manually segmented CLMs on T2 and T1-Hepatobiliary phase (T1-HBP) scans. After inter-observer variability testing, 148/182 RFs showed robustness on T1-HBP, and 141/182 on T2 (ICC > 0.7).Cox multivariate analysis was run to establish clinical (CLIN-mod), radiomic (RAD-T1, RAD-T2), and combined (COMB-T1, COMB-T2) models for LTPFS prediction. RESULTS: Seventy-six CLMs (43 patients) were assessed. Median follow-up was 14 months. LTP occurred in 19 lesions (25%).CLIN-mod was composed of minimal ablation margins (MAMs), intra-segment progression and primary tumor grade and exhibited moderately high discriminatory power in predicting LTPFS (AUC = 0.89, p = 0.0001). Both RAD-T1 and RAD-T2 were able to predict LTPFS: (RAD-T1: AUC = 0.83, p = 0.0003; RAD-T2: AUC = 0.79, p = 0.001). Combined models yielded the strongest performance (COMB-T1: AUC = 0.98, p = 0.0001; COMB-T2: AUC = 0.95, p = 0.0003). Both combined models included MAMs and tumor regression grade; COMB-T1 also featured 10th percentile of signal intensity, while tumor flatness was present in COMB-T2. CONCLUSION: MRI-based radiomic evaluation of CLMs is feasible and potentially useful for LTP prediction. Combined models outperformed clinical or radiomic models alone for LTPFS prediction.