Development and external validation of MRI-based RAS mutation status prediction model for liver metastases of colorectal cancer.

BACKGROUND: The mutation status of rat sarcoma viral oncogene homolog (RAS) has prognostic significance and serves as a key predictive biomarker for the effectiveness of antiepidermal growth factor receptor (EGFR) therapy. However, there remains a lack of effective models for predicting RAS mutation status in colorectal liver metastases (CRLMs). This study aimed to construct and validate a diagnostic model for predicting RAS mutation status among patients undergoing hepatic resection for CRLMs. METHODS: A diagnostic multivariate prediction model was developed and validated in patients with CRLMs who had undergone hepatectomy between 2014 and 2020. Patients from Institution A were assigned to the model development group (i.e., Development Cohort), while patients from Institutions B and C were assigned to the external validation groups (i.e., Validation Cohort_1 and Validation Cohort_2). The presence of CRLMs was determined by examination of surgical specimens. RAS mutation status was determined by genetic testing. The final predictors, identified by a group of oncologists and radiologists, included several key clinical, demographic, and radiographic characteristics derived from magnetic resonance images. Multiple imputation was performed to estimate the values of missing non-outcome data. A penalized logistic regression model using the adaptive least absolute shrinkage and selection operator penalty was implemented to select appropriate variables for the development of the model. A single nomogram was constructed from the model. The performance of the prediction model, discrimination, and calibration were estimated and reported by the area under the receiver operating characteristic curve (AUC) and calibration plots. Internal validation with a bootstrapping procedure and external validation of the nomogram were assessed. Finally, decision curve analyses were used to characterize the clinical outcomes of the Development and Validation Cohorts. RESULTS: A total of 173 patients were enrolled in this study between January 2014 and May 2020. Of the 173 patients, 117 patients from Institution A were assigned to the Model Development group, while 56 patients (33 from Institution B and 23 from Institution C) were assigned to the Model Validation groups. Forty-six (39.3%) patients harbored RAS mutations in the Development Cohort compared to 14 (42.4%) in Validation Cohort_1 and 8 (34.8%) in Validation Cohort_2. The final model contained the following predictor variables: time of occurrence of CRLMs, location of primary lesion, type of intratumoral necrosis, and early enhancement of liver parenchyma. The diagnostic model based on clinical and MRI data demonstrated satisfactory predictive performance in distinguishing between mutated and wild-type RAS, with AUCs of 0.742 (95% confidence interval [CI]: 0.651─0.834), 0.741 (95% CI: 0.649─0.836), 0.703 (95% CI: 0.514─0.892), and 0.708 (95% CI: 0.452─0.964) in the Development Cohort, bootstrapping internal validation, external Validation Cohort_1 and Validation Cohort_2, respectively. The Hosmer-Lemeshow goodness-of-fit values for the Development Cohort, Validation Cohort_1 and Validation Cohort_2 were 2.868 (p = 0.942), 4.616 (p = 0.465), and 6.297 (p = 0.391), respectively. CONCLUSIONS: Integrating clinical, demographic, and radiographic modalities with a magnetic resonance imaging-based approach may accurately predict the RAS mutation status of CRLMs, thereby aiding in triage and possibly reducing the time taken to perform diagnostic and life-saving procedures. Our diagnostic multivariate prediction model may serve as a foundation for prognostic stratification and therapeutic decision-making.

The association of carbohydrate antigen 19-9 response with radiologic response and survival in intrahepatic cholangiocarcinoma: A prospective cohort study.

BACKGROUND: The role of carbohydrate antigen 19-9 (CA 19-9) in response assessment among patients with intrahepatic cholangiocarcinoma (iCCA) remains unknown. The authors studied the association of the CA 19-9 response (defined as a reduction >50% from baseline) with the radiologic response and the outcome in patients with unresectable iCCA. METHODS: A prospective cohort of 422 patients who were initially diagnosed with unresectable iCCA, had baseline CA 19-9 levels ≥100 U/mL, and received treatment with systemic therapies at the authors' institution between January 2017 and December 2021 were enrolled in this study. The radiologic response was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1. A landmark assessment of the CA 19-9 response and the radiologic response was performed. The associations between CA 19-9 response and imaging response, progression-free survival (PFS), and overall survival (OS) were analyzed. RESULTS: Two hundred sixty-seven patients (63.3%) had a CA 19-9 response. A CA 19-9 response was observed in 123 of 132 (93.2%) radiologic responders and in 144 of 290 (49.7%) radiologic nonresponders (p < .001). CA 19-9 responders outperformed nonresponders in median PFS (10.6 vs. 3.6 months; hazard ratio [HR], 4.8 months; 95% confidence interval [CI], 3.8-6.0 months; p < .001) and OS (21.4 vs. 6.3 months; HR, 5.3 months; 95% CI, 4.2-6.7 months; p < .001). The common independent predictors of both OS and PFS included metastasis, CA 19-9 nonresponder status, and radiologic nonresponder status in multivariable analysis. CONCLUSIONS: CA 19-9 response is a valuable addition to assess tumor response and is associated with improved outcomes in patients with iCCA. Achieving a CA 19-9 response should be one of the therapeutic objectives of patients with iCCA after systemic therapies. PLAIN LANGUAGE SUMMARY: A decline in carbohydrate antigen 19-9 levels from elevated baseline levels should be one of the therapeutic aims of patients with intrahepatic cholangiocarcinoma who are managed with systemic therapies.

The value of CT findings combined with inflammatory indicators for preoperative differentiation of benign and malignant gallbladder polypoid lesions.

BACKGROUND: The study aimed to explore the value of CT findings and inflammatory indicators in differentiating benign and malignant gallbladder polypoid lesions before surgery. METHODS: The study comprised a total of 113 pathologically confirmed gallbladder polypoid lesions with a maximum diameter ≥ 1 cm (68 benign and 45 malignant), all of which were enhanced CT-scanned within 1 month before surgery. The CT findings and inflammatory indicators of the patients were analyzed by univariate and multivariate logistic regression analysis to identify independent predictors of gallbladder polypoid lesions, and then a nomogram distinguishing benign and malignant gallbladder polypoid lesions was developed by combining these characteristics. The receiver operating characteristic (ROC) curve and decision curve were plotted to assess the performance of the nomogram. RESULTS: Base status of the lesion (p < 0.001), plain CT value (p < 0.001), neutrophil-lymphocyte ratio (NLR) (p = 0.041), and monocyte-lymphocyte ratio (MLR) (p = 0.022) were independent predictors of malignant polypoid lesions of the gallbladder. The nomogram model established by incorporating the above factors had good performance in differentiating and predicting benign and malignant gallbladder polypoid lesions (AUC = 0.964), with sensitivity and specificity of 82.4% and 97.8%, respectively. The DCA demonstrated the important clinical utility of our nomogram. CONCLUSION: CT findings combined with inflammatory indicators can effectively differentiate benign and malignant gallbladder polypoid lesions before surgery, which is valuable for clinical decision-making.

Radiomics-Based Preoperative Prediction of Lymph Node Metastasis in Intrahepatic Cholangiocarcinoma Using Contrast-Enhanced Computed Tomography.

BACKGROUND: Lymph node (LN) metastasis is significantly associated with worse prognosis for patients with intrahepatic cholangiocarcinoma (ICC). Improvement in preoperative assessment on LN metastasis helps in treatment decision-making. We aimed to investigate the role of radiomics-based method in predicting LN metastasis for patients with ICC. METHODS: A total of 296 patients with ICC who underwent curative-intent hepatectomy and lymphadenectomy at two centers in China were analyzed. Radiomic features, including histogram- and wavelet-based features, shape and size features, and texture features were extracted from four-phase computerized tomography (CT) images. The clinical and conventional radiological variables which were independently associated with LN metastasis were also identified. A combined nomogram predicting LN metastasis was developed, and its performance was determined by discrimination, calibration, and stratification of long-term prognosis. The results were validated by the internal and external validation cohorts. RESULTS: Twenty-four radiomic features were selected into the nomogram. The established nomogram demonstrated good discrimination and calibration, with areas under the curve (AUCs) of 0.98 [95% confidence interval (CI) 0.96-0.99], 0.93 (0.88-0.98), and 0.89 (0.81-0.96) in the training and two validation cohorts, respectively. The 5-year overall survival (OS) and recurrence-free survival (RFS) rates of patients with high risk of LN metastasis as grouped by nomogram were poorer than those of patients with low risk in the training cohort (OS 28.8% versus 53.9%, p < 0.001; RFS 26.3% versus 44.2%, p = 0.001). Similar results were observed in the two validation cohorts. CONCLUSIONS: Radiomics-based method provided accurate prediction of LN metastasis and prognostic assessment for ICC patients, and might aid the preoperative surgical decision.

Prediction of HCC microvascular invasion with gadobenate-enhanced MRI: correlation with pathology.

PURPOSE: To assess the accuracy of gadobenate-enhanced MRI for predicting microvascular invasion (MVI) in patients operated for hepatocellular carcinoma (HCC). METHODS: The 164 patients who met the inclusion criteria were assigned to one of two groups: the MVI-positive group and the MVI-negative group. Imaging results were compared between the two groups using the Kruskal test, chi-square test, independent sample t test, and logistic regression analysis. RESULTS: Differences in the capsule (p = 0.037) and margin (p = 0.004) of the tumor, rim enhancement (p = 0.002), peritumoral enhancement in the arterial phase (p < 0.001), and peritumoral hypointensity in the hepatobiliary phase (HBP) (p < 0.001) were statistically significant. The results of multivariate analysis identified rim enhancement in the arterial phase (odds ratio (OR) = 2.115; 95% confidence interval (CI), 1.002-4.464; p = 0.049) and peritumoral hypointensity in the HBP (OR = 5.836; 95% CI, 2.442-13.948; p < 0.001) as independent risk factors for MVI. Use of the two predictors in combination identified 32.79% (20/61) of HCCs with MVI with a specificity of 95.15% (98/103). CONCLUSIONS: Rim enhancement in the arterial phase and peritumoral hypointensity in the HBP were identified as independent risk factors for MVI in patients with HCC. KEY POINTS: • Rim enhancement in the arterial phase and peritumoral hypointensity in the hepatobiliary phase were independent risk factors for microvascular invasion in patients with HCC. • Use of the two predictors in combination had a sensitivity of 32.79% and a specificity of 95.15% for predicting microvascular invasion.

Arterial hyperenhancement of small intrahepatic cholangiocarcinomas correlates with microvessel counts and patient survival.

BACKGROUND: To compare outcomes of patients with arterially hyperenhancing intrahepatic cholangiocarcinomas (ICC) and arterially hypoenhancing ICCs after partial hepatectomy in a cohort with an analysis of prognostic factors. METHODS: From June 2009 to October 2011, a prospective cohort of 68 patients with single resectable ICCs (≤5 cm in diameter) underwent gadolinium contrast-enhanced dynamic-phase magnetic resonance imaging and were treated with partial hepatectomy. Patients were divided into those with arterially hyperenhancing ICCs (n = 28) or arterially hypoenhancing ICCs (n = 40). Clinic-radiologic-pathologic results and survival of these patients were compared and statistically analyzed. RESULTS: The median overall survival (OS) time was significantly longer in the arterially hyperenhancing ICCs (56.8 vs. 37.0 months) (p = 0.044). At pathologic evaluation, arterially hyperenhancing ICCs showed significantly higher microvessel count (MVC) than arterially hypoenhancing ICCs (106.2 ± 47.5 vs. 46.9 ± 21.6/mm2, p = 0.001). Arterial enhancement of ICCs was found to be an independent prognostic factor for longer survival. CONCLUSION: The presence of arterially hyperenhancing ICCs is related to higher MVC and exhibit a better OS time than arterially hypoenhancing ICCs after partial hepatectomy.

Detection of liver metastases on gadobenate dimeglumine-enhanced MRI: systematic review, meta-analysis, and similarities with gadoxetate-enhanced MRI.

OBJECTIVES: To determine the sensitivity and positive predictive value (PPV) of gadobenate-enhanced MR imaging for the detection of liver metastases. METHODS: This systematic review and meta-analysis was conducted according to PRISMA guidelines. A comprehensive search (EMBASE, PubMed) was performed to identify relevant articles up to December 2017. Studies eligible for inclusion were performed using appropriate methodology with complete verification by means of histopathology, intraoperative observation and/or follow-up, and sufficient information to permit determination of true-positive (TP), false-negative (FN), and false-positive (FP) values. Sources of bias were assessed using the QUADAS-2 tool. An inverse variance-weighted random-effects model was used to obtain sensitivity and PPV estimates. Information was analyzed and presented using Cochran's Q statistic, funnel plots, and modified Deeks' analysis. RESULTS: Ten articles (256 patients, 562 metastases) were included. Sensitivity estimates for pre-contrast (unenhanced) imaging, gadobenate-enhanced dynamic imaging, and combined unenhanced, dynamic, and delayed hepatobiliary phase imaging for detecting liver metastases on a per-lesion basis were 77.8% (95% CI 71.4-84.3%, 7 assessments), 88.1% (95% CI, 84.0-92.2%, 13 assessments), and 95.1% (95% CI 93.1-97.1%, 15 assessments), respectively. The addition of hepatobiliary phase images significantly improved the detection of liver metastases. The overall PPV was 90.9% (95% CI 86.6-95.1%, 11 assessments). Deeks' funnel analysis revealed no association between sample size and sensitivity (ß = 0.02, p = 0.814) indicating no significant publication bias. CONCLUSIONS: Gadobenate-enhanced MR imaging has high sensitivity and PPV for the detection of liver metastases on a per-lesion basis. The sensitivity and PPV for detection is comparable to reported values for the pure liver-specific agent gadoxetate. KEY POINTS: • Gadobenate dimeglumine is a hepatobiliary MR contrast agent that permits acquisition of contrast-enhanced liver images during the immediate post-injection dynamic phase, like any extracellular agent, and in the delayed hepatobiliary phase, after specific uptake by the hepatocytes. • The hepatobiliary phase improves detection of liver metastases when compared either to pre-contrast unenhanced images alone or to pre-contrast + gadobenate-enhanced dynamic phase images. • The meta-analysis showed an overall sensitivity of 95.1% and PPV of 90.9% of gadobenate-enhanced MRI for the detection of metastases, when based on the evaluation of all available acquisitions.

18F- FDG PET/CT helps differentiate autoimmune pancreatitis from pancreatic cancer.

BACKGROUND: 18F-FDG PET/CT could satisfactorily show pancreatic and extra-pancreatic lesions in AIP, which can be mistaken for pancreatic cancer (PC). This study aimed to identify 18F-FDG PET/CT findings that might differentiate AIP from PC. METHODS: FDG-PET/CT findings of 26 AIP and 40 PC patients were reviewed. Pancreatic and extra-pancreatic lesions related findings, including maximum standardized uptake values (SUVmax) and patterns of FDG uptake, were identified and compared. RESULTS: All 26 patients with AIP had increased pancreatic FDG uptake. Focal abnormal pancreatic FDG activities were found in 38/40 (95.00%) PC patients, while longitudinal were found in 18/26 (69.23%) AIP patients. SUVmax was significantly different between AIP and PC, both in early and delayed PET/CT scans (p < 0.05). AUCs were 0.700 (early SUVmax), 0.687 (delayed SUVmax), 0.683 (early lesions/liver SUVmax), and 0.715 (delayed lesion/liver SUVmax). Bile duct related abnormalities were found in 12/26 (46.15%) AIP and 10/40 (25.00%) PC patients, respectively. Incidentally, salivary and prostate gland SUVmax in AIP patients were higher compared with those of PC patients (p < 0.05). In males,an inverted "V" shaped high FDG uptake in the prostate was more frequent in AIP than PC patients (56.00%, 14/25 vs. 5.71%, 2/35). Increased FDG activity in extra-pancreatic bile duct was present in 4/26 of AIP patients, while was observed in none of the PC patients. Only in AIP patients, both diffuse pancreatic FDG accumulation and increased inverted "V" shaped FDG uptake in the prostate could be found simultaneously. CONCLUSIONS: 18F-FDG PET/CT findings might help differentiate AIP from PC.

Small Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma in Cirrhotic Livers May Share Similar Enhancement Patterns at Multiphase Dynamic MR Imaging.

Purpose To assess the accuracy of magnetic resonance (MR) imaging-based differential diagnosis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) in a cohort of patients with focal liver lesions and cirrhosis. Materials and Methods This study was institutional review board approved, and the requirement for informed consent was waived. Between January 2009 and December 2014, a cohort of cirrhotic patients, including 71 with ICC and 612 with HCC, underwent unenhanced T1- and T2-weighted MR imaging, gadolinium-based contrast material-enhanced dynamic phase imaging, and partial hepatectomy. Results of pathologic examinations were obtained for all patients. Clinical, radiologic, and pathologic results in these patients were analyzed and compared comprehensively. Differences in signal intensity on baseline and contrast material-enhanced images and dynamic enhancement patterns were evaluated and compared by using the χ(2) test or the Fisher exact test. Results The preoperative diagnoses of 517 of 683 lesions were confirmed pathologically. Five ICCs and 481 HCCs displayed contrast material washout in delayed phases (P < .001). Thirty-six ICCs and 23 HCCs displayed a progressive enhancement pattern (P < .001). Twenty-six ICCs and 63 HCCs displayed a stable enhancement pattern (P < .001). ICCs displayed significantly different enhancement patterns according to size (P = .022). Conclusion The accurate discrimination of small ICCs from HCCs in the setting of cirrhosis at MR imaging is difficult, as substantial proportions of ICCs and HCCs have similar enhancement patterns. Absence of contrast material washout at MR imaging is not a factor that prevents the misdiagnosis of HCC. (©) RSNA, 2016 Online supplemental material is available for this article.

Cannabinoid CB2 receptor as a new phototherapy target for the inhibition of tumor growth.

The success of targeted cancer therapy largely relies upon the selection of target and the development of efficient therapeutic agents that specifically bind to the target. In the current study, we chose a cannabinoid CB2 receptor (CB2R) as a new target and used a CB2R-targeted photosensitizer, IR700DX-mbc94, for phototherapy treatment. IR700DX-mbc94 was prepared by conjugating a photosensitizer, IR700DX, to mbc94, whose binding specificity to CB2R has been previously demonstrated. We found that phototherapy treatment using IR700DX-mbc94 greatly inhibited the growth of CB2R positive tumors but not CB2R negative tumors. In addition, phototherapy treatment with nontargeted IR700DX did not show significant therapeutic effect. Similarly, treatment with IR700DX-mbc94 without light irradiation or light irradiation without the photosensitizer showed no tumor-inhibitory effect. Taken together, IR700DX-mbc94 is a promising phototherapy agent with high target-specificity. Moreover, CB2R appears to have great potential as a phototherapeutic target for cancer treatment.

Comparison of MRI features for the differentiation of hepatic angiomyolipoma from fat-containing hepatocellular carcinoma.

OBJECTIVE: The purpose of this study was to evaluate MRI features for the differentiation of hepatic angiomyolipoma (HAML) from fat-containing hepatocellular carcinoma. METHODS: We retrospectively reviewed the MRI findings of 20 patients with 22 hepatic angiomyolipomas and 25 patients with fat-containing hepatocellular carcinomas before surgery. The MRI features and apparent diffusion coefficient (ADC) for the two types of tumors were compared and analyzed. RESULTS: Fat was not detected in nine (40.9%) of the angiomyolipomas. An enhancement pattern of the washout area was seen in eight (36.4%) of the angiomyolipomas and 21 of the hepatocellular carcinomas (84%) (p = 0.001). The sensitivity, specificity, and accuracy of the enhancement pattern for HAML were 63.6% (14/22), 84% (21/25), and 74.5% (35/47), respectively. An early draining vein was seen in 16 (72.7%) angiomyolipomas and two hepatocellular carcinomas (8%) (p < 0.001). The sensitivity, specificity, and accuracy of an early draining vein for detecting HAML was 72.7% (16/22), 92% (23/25), and 83.0% (39/47), respectively. Tumor vessels were noted in 18 (81.8%) angiomyolipomas and six hepatocellular carcinomas (24%) (p < 0.001). The sensitivity, specificity, and accuracy of tumor vessels for HAML were 81.8% (18/22), 76% (19/25), and 78.7% (37/47), respectively. Pseudocapsules were absent in 21 (95.5%) angiomyolipomas as compared with 3 (12%) hepatocellular carcinomas (p < 0.001). The sensitivity, specificity, and accuracy of pseudocapsules for HAML were 95.5% (21/22), 88% (22/25), and 91.5% (43/47), respectively. The ADC of the angiomyolipomas (1.92 ± 0.29 × 10(-3 )mm(2)/s) was significantly higher than that for hepatocellular carcinomas (1.33 ± 0.25 × 10(-3 )mm(2)/s) (p < 0.001). CONCLUSION: The presence of an early draining vein and tumor vessels, the absence of pseudocapsules and a higher ADC in the hypervascular hepatic tumor on the MRI were helpful for the differentiation of hepatic angiomyolipoma from fat-containing hepatocellular carcinoma.

Prediction of Microvascular Invasion and Recurrence After Curative Resection of LI-RADS Category 5 Hepatocellular Carcinoma on Gd-BOPTA Enhanced MRI.

Objective: This study aims to investigate the predictive value of Gadobenate dimeglumine (Gd-BOPTA) enhanced MRI features on microvascular invasion (MVI) and recurrence in patients with Liver Imaging Reporting and Data System (LI-RADS) category 5 hepatocellular carcinoma (HCC). Methods: A total of 132 patients with LI-RADS category 5 HCC who underwent curative resection and Gd-BOPTA enhanced MRI at our hospital between January 2016 and December 2018 were retrospectively analyzed. Qualitative evaluation based on LI-RADS v2018 imaging features was performed. Logistic regression analyses were conducted to assess the predictive significance of these features for MVI, and the Cox proportional hazards model was used to identify postoperative risk factors of recurrence. The recurrence-free survival (RFS) was analyzed by using the Kaplan-Meier curve and Log rank test. Results: Multivariate logistic regression analysis identified that corona enhancement (odds ratio [OR] = 3.217; p < 0.001), internal arteries (OR = 4.147; p = 0.004), and peritumoral hypointensity on hepatobiliary phase (HBP) (OR = 5.165; p < 0.001) were significantly associated with MVI. Among the 132 patients with LR-5 HCC, 62 patients experienced postoperative recurrence. Multivariate Cox regression analysis showed that mosaic architecture (hazard ratio [HR] = 1.982; p = 0.014), corona enhancement (HR = 1.783; p = 0.039), and peritumoral hypointensity on HBP (HR = 2.130; p = 0.009) were risk factors for poor RFS. Conclusion: MRI features based on Gd-BOPTA can be noninvasively and effectively predict MVI and recurrence of LR-5 HCC patients.

Preoperative evaluation of MRI features and inflammatory biomarkers in predicting microvascular invasion of combined hepatocellular cholangiocarcinoma.

PURPOSE: Microvascular invasion (MVI) is a significant prognostic factor in combined hepatocellular cholangiocarcinoma (cHCC-CCA). However, its diagnosis relies on postoperative histopathologic analysis. This study aims to identify preoperative inflammatory biomarkers and MR-imaging features that can predict MVI in cHCC-CCA. METHODS: This retrospective study enrolled 119 patients with histopathologically confirmed cHCC-CCA between January 2016 and December 2021. Two radiologists, unaware of the clinical data, independently reviewed all MR image features. Univariable and multivariable analyses were performed to determine the independent predictors for MVI among inflammatory biomarkers and MRI characteristics. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the diagnostic performance. RESULTS: Multivariable logistic regression analysis identified four variables significantly associated with MVI (p < 0.05), including two inflammatory biomarkers [albumin-to-alkaline phosphatase ratio (AAPR) and aspartate aminotransferase-to-neutrophil ratio index (ANRI)] and two MRI features (non-smooth tumor margin and arterial phase peritumoral enhancement). A combined model for predicting MVI was constructed based on these four variables, with an AUC of 0.802 (95% CI 0.719-0.870). The diagnostic efficiency of the combined model was higher than that of the imaging model. CONCLUSION: Inflammatory biomarkers and MRI features could be potential predictors for MVI in cHCC-CCA. The combined model, derived from inflammatory biomarkers and MRI features, showed good performance in preoperatively predicting MVI in cHCC-CCA patients.

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Hepatocellular carcinoma (HCC) is one of the most common malignancies and is a major cause of cancer-related mortalities worldwide (Forner et al., 2018; He et al., 2023). Sarcopenia is a syndrome characterized by an accelerated loss of skeletal muscle (SM) mass that may be age-related or the result of malnutrition in cancer patients (Cruz-Jentoft and Sayer, 2019). Preoperative sarcopenia in HCC patients treated with hepatectomy or liver transplantation is an independent risk factor for poor survival (Voron et al., 2015; van Vugt et al., 2016). Previous studies have used various criteria to define sarcopenia, including muscle area and density. However, the lack of standardized diagnostic methods for sarcopenia limits their clinical use. In 2018, the European Working Group on Sarcopenia in Older People (EWGSOP) renewed a consensus on the definition of sarcopenia: low muscle strength, loss of muscle quantity, and poor physical performance (Cruz-Jentoft et al., 2019). Radiological imaging-based measurement of muscle quantity or mass is most commonly used to evaluate the degree of sarcopenia. The gold standard is to measure the SM and/or psoas muscle (PM) area using abdominal computed tomography (CT) at the third lumbar vertebra (L3), as it is linearly correlated to whole-body SM mass (van Vugt et al., 2016). According to a "North American Expert Opinion Statement on Sarcopenia," SM index (SMI) is the preferred measure of sarcopenia (Carey et al., 2019). The variability between morphometric muscle indexes revealed that they have different clinical relevance and are generally not applicable to broader populations (Esser et al., 2019).

Optimizing predictions: improved performance of preoperative gadobenate-enhanced MRI hepatobiliary phase features in predicting vessels encapsulating tumor clusters in hepatocellular carcinoma-a multicenter study.

BACKGROUND: Vessels Encapsulating Tumor Clusters (VETC) are now recognized as independent indicators of recurrence and overall survival in hepatocellular carcinoma (HCC) patients. However, there has been limited investigation into predicting the VETC pattern using hepatobiliary phase (HBP) features from preoperative gadobenate-enhanced MRI. METHODS: This study involved 252 HCC patients with confirmed VETC status from three different hospitals (Hospital 1: training set with 142 patients; Hospital 2: test set with 64 patients; Hospital 3: validation set with 46 patients). Independent predictive factors for VETC status were determined through univariate and multivariate logistic analyses. Subsequently, these factors were used to construct two distinct VETC prediction models. Model 1 included all independent predictive factors, while Model 2 excluded HBP features. The performance of both models was assessed using the Area Under the Curve (AUC), Decision Curve Analysis, and Calibration Curve. Prediction accuracy between the two models was compared using Net Reclassification Improvement (NRI) and Integrated Discriminant Improvement (IDI). RESULTS: CA199, IBIL, shape, peritumoral hyperintensity on HBP, and arterial peritumoral enhancement were independent predictors of VETC. Model 1 showed robust predictive performance, with AUCs of 0.836 (training), 0.811 (test), and 0.802 (validation). Model 2 exhibited moderate performance, with AUCs of 0.813, 0.773, and 0.783 in the respective sets. Calibration and decision curves for both models indicated consistent predictions between predicted and actual VETC, benefiting HCC patients. NRI showed Model 1 increased by 0.326, 0.389, and 0.478 in the training, test, and validation sets compared to Model 2. IDI indicated Model 1 increased by 0.036, 0.028, and 0.025 in the training, test, and validation sets compared to Model 2. CONCLUSION: HBP features from preoperative gadobenate-enhanced MRI can enhance the predictive performance of VETC in HCC.

Nomogram prediction of vessels encapsulating tumor clusters in small hepatocellular carcinoma ≤ 3 cm based on enhanced magnetic resonance imaging.

BACKGROUND: Vessels encapsulating tumor clusters (VETC) represent a recently discovered vascular pattern associated with novel metastasis mechanisms in hepatocellular carcinoma (HCC). However, it seems that no one have focused on predicting VETC status in small HCC (sHCC). This study aimed to develop a new nomogram for predicting VETC positivity using preoperative clinical data and image features in sHCC (≤ 3 cm) patients. AIM: To construct a nomogram that combines preoperative clinical parameters and image features to predict patterns of VETC and evaluate the prognosis of sHCC patients. METHODS: A total of 309 patients with sHCC, who underwent segmental resection and had their VETC status confirmed, were included in the study. These patients were recruited from three different hospitals: Hospital 1 contributed 177 patients for the training set, Hospital 2 provided 78 patients for the test set, and Hospital 3 provided 54 patients for the validation set. Independent predictors of VETC were identified through univariate and multivariate logistic analyses. These independent predictors were then used to construct a VETC prediction model for sHCC. The model's performance was evaluated using the area under the curve (AUC), calibration curve, and clinical decision curve. Additionally, Kaplan-Meier survival analysis was performed to confirm whether the predicted VETC status by the model is associated with early recurrence, just as it is with the actual VETC status and early recurrence. RESULTS: Alpha-fetoprotein_lg10, carbohydrate antigen 199, irregular shape, non-smooth margin, and arterial peritumoral enhancement were identified as independent predictors of VETC. The model incorporating these predictors demonstrated strong predictive performance. The AUC was 0.811 for the training set, 0.800 for the test set, and 0.791 for the validation set. The calibration curve indicated that the predicted probability was consistent with the actual VETC status in all three sets. Furthermore, the decision curve analysis demonstrated the clinical benefits of our model for patients with sHCC. Finally, early recurrence was more likely to occur in the VETC-positive group compared to the VETC-negative group, regardless of whether considering the actual or predicted VETC status. CONCLUSION: Our novel prediction model demonstrates strong performance in predicting VETC positivity in sHCC (≤ 3 cm) patients, and it holds potential for predicting early recurrence. This model equips clinicians with valuable information to make informed clinical treatment decisions.

Comparison of lung lesion biopsies between low-dose CT-guided and conventional CT-guided techniques.

BACKGROUND: The low-dose computed tomography (CT) technique has been widely used because it decreases the potential risk of radiation exposure, as well as enabling low-dose CT-guided lung lesion biopsy. However, uncertainties remain regarding diagnostic accuracy, radiation dose, complication rate, and image quality. PURPOSE: To compare the diagnostic accuracy, radiation dose, complication rate, and image quality of lung lesion biopsy between conventional CT-guided and low-dose CT-guided techniques. MATERIAL AND METHODS: A total of 90 patients were prospectively enrolled and randomized into two groups (group A: 120 kv; 200 mA; thickness, 2.0 mm; pitch, 16 mm/rot; n = 44; group B: 120 kv;10 mA; thickness, 2.0 mm; pitch, 23 mm/rot; n = 46). Sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), radiation dose, image quality, and complication rate were compared. All variables between the two groups were analyzed using chi-square and Student's t tests. A P value of < 0.05 was considered statistically significant. RESULTS: The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) for diagnosing lung lesions were 96.88%, 100%, 97.5%, 100%, and 88.89% in group A, respectively. In group B, the values were 96.67%, 100%, 97.5%, 100%, and 90.91%, respectively (P > 0.05). The mean weighted CT dose index (CTDIw) and dose-length product (DLP) were 29.29 ± 3.93 mGy and 211.74 ± 37.89 mGy*cm in group A and 1.55 ± 0.15 mGy and 10.98 ± 1.56 mGy*cm in group B (P < 0.001). Image quality satisfied the need for a coaxial biopsy. Complications in group A and group B were observed in 27.28% and 23.91% of the patients, respectively (P > 0.05). CONCLUSION: Compared to conventional CT-guided biopsies, lung lesion biopsies guided by the low-dose CT biopsy protocol showed dramatically lower CTDIw and DLP levels. In contrast, the diagnostic yield of the procedures did not differ significantly, which is a recommended technique in certain populations.

Prediction of microvascular invasion in combined hepatocellular-cholangiocarcinoma based on preoperative contrast-enhanced CT and clinical data.

OBJECTIVE: Microvascular invasion (MVI) is significantly associated with prognosis in combined hepatocellular-cholangiocarcinoma (cHCC-CCA) patients. The study aimed to explore the value of preoperative contrast-enhanced CT (CECT) features and clinical data in predicting MVI of cHCC-CCA. METHODS: A total of 33 patients with MVI-positive and 27 with MVI-negative were enrolled, and underwent preoperative CECT imaging from January 2016 to December 2021. Preoperative clinical data and CECT imaging features were retrospectively analyzed. Univariable and multivariable logistic regression analysis were performed to identify potential predictors of MVI in cHCC-CCA. The diagnostic performance was evaluated by the receiver operating characteristic (ROC) curve and its area under the curve (AUC) value. RESULTS: The mean age of the patients was 54.0 ±â€¯10.3 years, and 53 of the 60 patients (88.3%) were male. Preoperative imaging features on CECT (non-smooth contour and arterial phase peritumoral enhancement) and clinical data (hepatitis B virus (HBV) infection and protein induced by vitamin K absence or antagonist-II (PIVKA-II)) were highly distinct between those in MVI-positive group and MVI-negative group. On multivariable logistic analysis, arterial phase peritumoral enhancement (odds ratio (OR), 6.514; 95% confidence interval (CI), 1.588-26.728, p = 0.012) and high serum PIVKA-II level (OR, 6.810; 95% CI, 1.796-25.820, p = 0.005) were independent predictors associated with MVI of cHCC-CCA. The combination of these two predictors had high sensitivity (31/33, 93.9%; 95% CI, 80.4% - 98.3%) in the prediction of MVI with an area under the receiver operating characteristic (ROC) curve of 0.763 (95% CI, 0.635-0.863). CONCLUSIONS: The findings indicated that arterial phase peritumoral enhancement on preoperative CECT and high serum PIVKA-II level were identified as potential predictors for MVI in cHCC-CCA patients.

Actual over 3-year survival after stereotactic body radiation therapy in patients with unresectable intrahepatic cholangiocarcinoma.

PURPOSE: As a non-invasive treatment, stereotactic body radiation therapy (SBRT) has been an emerging and effective option for patients with unresectable intrahepatic cholangiocarcinoma (ICC). The Cyber Knife has an SBRT system, which can realize real-time tracking of tumors during treatment. It can protect the surrounding normal liver tissue while the tumor gets the therapeutic dose. The purpose of this study was to evaluate the factors affecting the local control rate for patients after SBRT treatment, and to predict the factors affecting survival rates, then to report the 3-year actual survival rates after treatment and identify the influencing factors of 3-year survival rate. MATERIALS AND METHODS: We conducted a long-term follow-up of 43 patients with unresectable intrahepatic cholangiocarcinoma who underwent Cyber Knife in our hospital from January 2016 to December 2018. Regular medical check-ups were performed every 2-3 months after SBRT to evaluated the effect of treatment. RESULTS: The median follow-up time was 15 months (4-78 months), and the median progression-free survival (PFS) was 6 months (95% CI, 2.788-9.212) and the median overall survival (OS) was 12 months (95% CI, 3.434-20.566), respectively. Based on modified Response Evaluation and Criteria in Solid Tumor (mRECIST), response rate (RR) and disease control rate (DCR) of SBRT in unresectable ICC were 55.2% and 86%. The 1-, 2- and 3-years OS rate were 51.2%, 32.6% and 23.3%. Multivariate analysis based on competing risk survival analysis identified that patients with multiple nodules, large diameter, high level of CA199 and CEA, poor ECOG performance status had worse overall survival (p < 0.05). Patients who survived ≥3 years had significantly lower levels of CEA, CA199, smaller tumor diameters and lower number of lesions (p < 0.05). CONCLUSION: The SBRT might be a candidate option for patients who unable to perform surgery. The rate of 3-year survival after SBRT for unresectable ICC can be expected with 23.3%.