Metabolic dysfunction associated steatotic liver disease in patients with plaque psoriasis: a case-control study and serological comparison.

Background: The relationship between plaque psoriasis and both MASLD and lean MASLD has not been sufficiently explored in the current literature. Method: This retrospective and observational study was carried out from January 2021 to January 2023 at The First Affiliated Hospital of Zhejiang Chinese Medical University. Patients diagnosed with plaque psoriasis and a control group consisting of individuals undergoing routine physical examinations were enrolled. The incidence of MASLD and lean MASLD among these groups was compared. Additionally, patients with plaque psoriasis were divided into those with MASLD, those with lean MASLD, and a control group with only psoriasis for a serological comparative analysis. Results: The incidence of MASLD in the observation group and the control group was 43.67% (69/158) and 22.15% (35/158), respectively (p < 0.01). Furthermore, the incidence of lean MASLD within the observation group and the control group was 10.76% (17/158) and 4.43% (7/158), respectively (p < 0.01). After controlling for potential confounding variables, plaque psoriasis was identified as an independent risk factor for MASLD with an odds ratio of 1.88 (95% cl: 1.10-3.21). In terms of serological comparison, compared to the simple psoriasis group, we observed a significant elevation in the tumor marker CYFRA21-1 levels in both groups compared to the control group with simple psoriasis (p < 0.01). Moreover, the MASLD group exhibited elevated levels of inflammatory markers and psoriasis score, whereas these effects were mitigated in the lean MASLD group. Conclusion: The prevalence of MASLD and lean MASLD is higher among patients with psoriasis. Those suffering from psoriasis along with MASLD show increased psoriasis scores and inflammatory markers compared to those without metabolic disorders. MASLD likely worsens psoriasis conditions, indicating the necessity of targeted health education for affected individuals to reduce the risk of MASLD, this education should include guidelines on exercise and diet. In serological assessments, elevated levels of cytokeratin 19 fragment (CYFRA21-1) were noted in both MASLD and lean MASLD groups, implying a potential synergistic role between psoriasis and MASLD.

Improved diagnostic accuracy with three lung tumor markers compared to six-marker panel.

Background: Combining multiple tumor markers increases sensitivity for lung cancer diagnosis in the cost of false positive. However, some would like to check as many as tumor markers in the fear of missing cancer. We though to propose a panel of fewer tumor markers for lung cancer diagnosis. Methods: Patients with suspected lung cancer who simultaneously underwent all six tests [carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA), squamous cell carcinoma-associated antigen (SCC), neuron-specific enolase (NSE), pro-gastrin-releasing peptide (ProGRP), and sialyl Lewis-X antigen (SLX)] were included. Tumor markers with significant impact on the lung cancer in a logistic regression model were included in our panel. Area under the curve (AUC) was compared between our panel and the panel of all six. Results: We included 1,733 [median 72 years, 1,128 men, 605 women, 779 (45%) confirmed lung cancer]. Logistic regression analysis suggested CEA, CYFRA, and NSE were independently associated with the lung cancer diagnosis. The panel of these three tumor markers [AUC =0.656, 95% confidence interval (CI): 0.630-0.682, sensitivity 0.650, specificity 0.662] had better (P<0.001) diagnostic performance than six tumor markers (AUC =0.575, 95% CI: 0.548-0.602, sensitivity 0.829, specificity 0.321). Conclusions: Compared to applying all six markers (at least one marker above the upper limit of normal), the panel with three markers (at least one marker above the upper limit of normal) led to a better predictive value by lowering the risk of false positives.

Intrahepatic mucinous cholangiocarcinoma with recurrent colic in a horse case report and literature review of cholangiocarcinoma in horses.

A 17-y-old Arabian mare was presented to the Auburn Large Animal Veterinary Teaching Hospital with a long-term history of intermittent mild recurrent colic that responded to medical treatment. CBC revealed mild lymphopenia; serum biochemistry findings were of increased gamma-glutamyl transferase and creatine kinase activities, hyperferremia, hyperglycemia, hypomagnesemia, and hypokalemia. Abdominocentesis was compatible with low-protein transudate. Due to the progression and duration of clinical signs, the owner elected euthanasia. Postmortem examination and histopathology confirmed a cholangiocarcinoma. The neoplastic cells were arranged in large cysts containing lakes of mucin that comprised 90% of the tumor volume; thus, a mucinous variant was determined. The neoplastic cells had strong cytoplasmic immunolabeling for cytokeratin 19 and lacked immunolabeling for hepatocyte paraffin 1, supporting bile duct origin. Cholangiocarcinomas are infrequent tumors in horses with nonspecific and slow progressive clinical signs, including recurrent colic. Mucinous cholangiocarcinomas are seldom reported in veterinary medicine and, to our knowledge, have not been reported previously in horses.

p53, Cytokeratin 19 Expression in Oral Squamous Cell Carcinoma and Correlation with Histopathologic Grading: An Immunohistochemical Study.

The purpose of this study was to examine the immunohistochemical expression of p53 and cytokeratin 19 (CK19) in normal oral mucosa (NOM) and oral squamous cell carcinoma (OSCC) and their association with histopathological differentiation grade. The secondary goal was to see if there was any correlation between p53 and CK19 expression in NOM and OSCC. A hospital-based retrospective analysis was conducted in which 40 NOM and 45 OSCC samples were acquired from archives and stained with mouse monoclonal antibodies p53 and CK19. For both the NOM and OSCC groups, the proportion of positively stained cells, staining intensity, and staining index were calculated. p53 immunoexpression revealed that 85% of positively stained cells in the NOM basal layer had a low staining index (mean ± SD 1.87 ± 0.34), whereas 66.7% of positively stained cells in the OSCC had a high staining index (mean ± SD 5.63 ± 3.02). When NOM and OSCC were compared, there was a statistically significant difference in staining intensity. However, despite a linear increase in the percentage of positive cells from well to poorly differentiated, the comparison between histopathological grades was non-significant. CK19 exhibited 18.5% positively stained cells in the NOM basal layer with a low staining index (mean ± SD 1.57 ± 0.53), whereas OSCC samples showed 4.44% immunopositivity with a high staining index. p53 is a marker of oral carcinogenesis independent of histological grade and CK19 expression. Further, CK19 is a marker of dysfunctional epithelial differentiation but lacks sensitivity and specificity; however, it demands further multicentric studies with a large sample size to draw definitive conclusions. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-04092-7.

A Co-Reactive Immunosensor Based on Ti3C2Tx MXene@TiO2-MoS2 Hybrids Promoting luminol@Au@Ni-Co NCs Electrochemiluminescence for CYFRA 21-1 Detection.

The construction of assays is capable of accurately detecting cytokeratin-19 (CYFRA 21-1), which is critical for the rapid diagnosis of nonsmall cell lung cancer. In this work, a novel electrochemiluminescence (ECL) immunosensor based on the co-reaction promotion of luminol@Au@Ni-Co nanocages (NCs) as ECL probe by Ti3C2Tx MXene@TiO2-MoS2 hybrids as co-reaction accelerator was proposed to detect CYFRA 21-1. Ni-Co NCs, as a derivative of Prussian blue analogs, can be loaded with large quantities of Au NPs, luminol, and CYFRA 21-1 secondary antibodies due to their high specific surface area. To further improve the sensitivity of the developed ECL immunosensor, Ti3C2Tx MXene@TiO2-MoS2 hybrids were prepared by in situ growth of TiO2 nanosheets on highly conductive Ti3C2Tx MXene, and MoS2 was homogeneously grown on Ti3C2Tx MXene@TiO2 surfaces by the hydrothermal method. Ti3C2Tx MXene@TiO2-MoS2 hybrids possess excellent catalytic performance on the electro-redox of H2O2 generating more O2·- and obtaining optimal ECL intensity of the luminol/H2O2 system. Under the appropriate experimental conditions, the quantitative detection range of CYFRA 21-1 was from 0.1 pg mL-1 to 100 ng mL-1, and the limit of detection (LOD) was 0.046 pg mL-1. The present sensor has a lower LOD with a wider linear range, which provides a new analytical assay for the early diagnosis of small-cell-type lung cancer labels.

Serum CYFRA 21-1 Level as a Prognostic Marker for Extensive Disease Small Cell Lung Cancer.

BACKGROUND/AIM: Pretreatment serum cytokeratin 19 fragment (CYFRA21-1) level predicts outcomes in patients with non-small cell lung cancer; however, little is known about the clinical value of serum CYFRA21-1 level in patients with small cell lung cancer (SCLC). The aim of this study was to evaluate the prognostic value of pretreatment serum CYFRA21-1 level in patients with extensive disease (ED)-SCLC treated using platinum-doublet chemotherapy. PATIENTS AND METHODS: We retrospectively analyzed the pretreatment serum CYFRA21-1 levels of patients with ED-SCLC who were treated using first-line platinum-doublet chemotherapy. RESULTS: A total of 98 patients were analyzed. The patients with a high CYFRA21-1 level (≥7.0 ng/ml) (n=29) had significantly shorter progression-free survival (PFS) and overall survival (OS) than the patients with low CYFRA21-1 levels (n=67) [median PFS=118 days vs. 125 days, respectively (p=0.018); median OS=213 days vs. 295 days, respectively (p=0.046)]. In addition, high CYFRA21-1 level was associated with a high refractory relapse rate. CONCLUSION: Serum CYFRA21-1 level may be a prognostic marker for patients with ED-SCLC treated with platinum-doublet chemotherapy.

Predictive Value of Serum CYFRA 21-1 and CK19-2G2 for Tumor Aggressiveness and Overall Survival in Hepatitis C-Related Hepatocellular Carcinoma Among Egyptians: A Prospective Study.

PURPOSE: Cytokeratin 19 fragment 21-1 (CYFRA 21-1) and cytokeratin 19 fragment 2G2 (CK 19-2G2) are two soluble fragments of cytokeratin 19 (CK 19) that can be detected in serum. CK 19-positive hepatocellular carcinoma (HCC) is characterized by an aggressive behavior and a poor outcome. This study aimed to assess the prognostic value of serum CYFRA 21-1 and CK 19-2G2 in predicting tumor aggressiveness and overall survival (OS) in patients with hepatic C virus (HCV)-related HCC. METHODS: The current study included 138 patients with HCV-related HCC recruited from the Hepatobiliary and Interventional Radiology Units at Alexandria's main university hospitals and 40 healthy individuals as controls. Patients were assessed for clinical, radiological tumor characteristics, and aggressiveness index. Baseline serum CYFRA 21-1 and CK 19-2G2 levels were measured by enzyme-linked immunosorbent assay. RESULTS: Elevated CYFRA 21-1 levels were associated with tumors size ≥ 5 cm (p < 0.001), malignant portal vein thrombosis (mPVT) (p < 0.001), distant metastasis (p = 0.030), ill-defined/infiltrative pattern (p = 0.010), and aggressiveness index > 4 (p = 0.045). Elevated CK19-2G2 levels were not associated with any clinical or radiological characteristics. Either or both elevated serum CYFRA 21-1 and CK 19-2G2 in combination with alpha-feto protein (AFP) ≥ 400 ng/ml have a better predictability for mPVT and ill-defined/infiltrative patterns (sensitivity (10-25%) and specificity (96-100%)). Elevated levels of CYFRA 21-1, CK 19-2G2, or AFP ≥ 400 ng/ml were associated with decreased 1-year OS. CONCLUSIONS: Either or both elevated serum CYFRA 21-1 and CK 19-2G2 levels when added to AFP ≥ 400 ng/ml are specific but less sensitive biomarkers for predicting tumor aggressiveness. These biomarkers can be used independently to predict reduced 1-year OS in Egyptian patients with HCV-related HCC.

Fusion expression, purification, and characterization of cytokeratin 19 fragments in E. coli for enhanced stability in diagnostic applications.

Cytokeratin 19 fragment (CYFRA21-1) serves as a crucial tumor marker in the context of lung cancer patients, playing a pivotal role as a calibrator in the realm of in vitro diagnostics. Nevertheless, during practical application, it has come to light that the recombinantly synthesized full-length CYFRA21-1 antigen exhibits suboptimal stability at the requisite concentration, while the utilization of natural antigens incurs a substantial cost. To address this issue, our investigation harnessed a strategic approach whereby the soluble fragment of cytokeratin 19 (Aa244-400) was integrated into the pET32a vector, subsequently being expressed within E. coli through a fusion with the TrxA protein. This process involved induction of protein expression through 0.2 mM IPTG at 16 °C for a duration of 16 h. After induction, the target protein was purified through Ni affinity and ion exchange chromatography. Subsequent characterization of the targeted protein was executed through the SEC-HPLC technique. The attained CYFRA21-1 antigen, as generated within this study, was effectively incorporated into a chemiluminescence-based in vitro diagnostic detection kit. The results indicate that the fusion protein exhibited commendable reactivity and stability, manifesting a deviation of less than 10 % following incubation at 37 °C for 7 days. Importantly, the production yield achieved a notable magnitude of 300 mg/L, thus rendering it a cost-effective and scalable alternative to natural antigens for clinical diagnostic applications.

Quantification of the lung cancer tumor marker CYFRA 21-1 using protein precipitation, immunoaffinity bottom-up LC-MS/MS.

OBJECTIVES: Numerous studies have proven the potential of cytokeratin 19 fragment 21-1 (CYFRA 21-1) detection in the (early) diagnosis and treatment monitoring of non-small cell lung cancer (NSCLC). Conventional immunoassays for CYFRA 21-1 quantification are however prone to interferences and lack diagnostic sensitivity and standardization. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is an emerging approach based on a different, often superior, detection principle, which may improve the clinical applicability of CYFRA 21-1 in cancer diagnostics. Therefore, we developed and validated a protein precipitation, immunoaffinity (IA) LC-MS/MS assay for quantitative analysis of serum CYFRA 21-1. METHODS: Selective sample preparation was performed using ammonium sulfate (AS) precipitation, IA purification, tryptic digestion and LC-MS/MS quantification using a signature peptide and isotopically labeled internal standard. The workflow was optimized and validated according to EMA guidelines and results were compared to a conventional immunoassay. RESULTS: Significant interference effects were seen during IA purification, which were sufficiently solved by performing AS precipitation prior to IA purification. A linear calibration curve was obtained in the range of 1.0-100 ng/mL (R2=0.98). Accuracy and precision were well within acceptance criteria. In sera of patients suspected of lung cancer, the method showed good correlation with the immunoassay. CONCLUSIONS: A robust AS precipitation-IA LC-MS/MS assay for the quantification of serum CYFRA 21-1 was developed. With this assay, the clinically added value of LC-MS/MS-based detection over immunoassays can be further explored.

Preoperative prediction of cholangiocyte phenotype hepatocellular carcinoma on contrast-enhanced MRI and the prognostic implication after hepatectomy.

BACKGROUND: Hepatocellular carcinoma (HCC) expressing cytokeratin (CK) 7 or CK19 has a cholangiocyte phenotype that stimulates HCC proliferation, metastasis, and sorafenib therapy resistance This study aims to noninvasively predict cholangiocyte phenotype-positive HCC and assess its prognosis after hepatectomy. METHODS: Between January 2010 and May 2022, preoperative contrast-enhanced MRI was performed on consecutive patients who underwent hepatectomy and had pathologically confirmed solitary HCC. Two abdominal radiologists separately assessed the MRI features. A predictive model for cholangiocyte phenotype HCC was created using logistic regression analysis and five-fold cross-validation. A receiver operating characteristic curve was used to calculate the model performance. Kaplan-Meier and log-rank methods were used to evaluate survival outcomes. RESULTS: In total, 334 patients were included in this retrospective study. Four contrast-enhanced MRI features, including "rim arterial phase hyperenhancement" (OR = 5.9, 95% confidence interval [CI]: 2.9-12.0, 10 points), "nodule in nodule architecture" (OR = 3.5, 95% CI: 2.1-5.9, 7 points), "non-smooth tumor margin" (OR = 1.6, 95% CI: 0.8-2.9, 3 points), and "non-peripheral washout" (OR = 0.6, 95% CI: 0.3-1.0, - 3 points), were assigned to the cholangiocyte phenotype HCC prediction model. The area under the curves for the training and independent validation set were 0.76 and 0.73, respectively. Patients with model-predicted cholangiocyte phenotype HCC demonstrated lower rates of recurrence-free survival (RFS) and overall survival (OS) after hepatectomy, with an estimated median RFS and OS of 926 vs. 1565 days (p < 0.001) and 1504 vs. 2960 days (p < 0.001), respectively. CONCLUSIONS: Contrast-enhanced MRI features can be used to predict cholangiocyte phenotype-positive HCC. Patients with pathologically confirmed or MRI model-predicted cholangiocyte phenotype HCC have a worse prognosis after hepatectomy. CRITICAL RELEVANCE STATEMENT: Four contrast-enhanced MRI features were significantly associated with cholangiocyte phenotype HCC and a worse prognosis following hepatectomy; these features may assist in predicting prognosis after surgery and improve personalized treatment decision-making. KEY POINTS: • Four contrast-enhanced MRI features were significantly associated with cholangiocyte phenotype HCC. • A noninvasive cholangiocyte phenotype HCC predictive model was established based on MRI features. • Patients with cholangiocyte phenotype HCC demonstrated a worse prognosis following hepatic resection.

Evaluation of Cytokeratin-7 and Cytokeratin-19 Expression Relationship with Gleason Score in Prostatic Adenocarcinoma.

Background & Objective: Prostatic adenocarcinoma (PAC) is one of the most common tumors worldwide. Immunohistochemical expression of cytokeratins has been evaluated in the diagnosis and prognosis of tumors. The aim of the present study is the evaluation of Cytokeratin-7 (Ck-7) and Cytokeratin-19 (Ck-19) expression and its relationship with Gleason score in patients with PAC. Methods: In this cross-sectional study, 78 samples from 78 patients with PAC referred to Mostafa Khomeini Hospital were gathered. Samples were immunohistochemically stained by Ck-7 and Ck-19 markers. The percentage of each marker in tumor cells was determined, and its relationship with Gleason scores and Gleason grade groups was analysed by SPSS version 24. Results: The expression of Ck-7 and Ck-19 were seen in 37.2% and 82.1% of samples, respectively. The mean of Ck-7 expression in tumor cells was 4.98%±7.19 (ranged 0 to 26%), while the mean of Ck-19 expression was 41.02%±23.36 (ranged 0 to 78%). There was no relationship between Ck-7 expression with Gleason scores and Gleason grade groups. However, Ck-19 expression was increased in higher Gleason scores and Gleason grade groups (P<0.001). No relationship was found between age and Ck-7 (P=0.309) and Ck-19 (P=0.375). Conclusion: The Ck-7 expression in PAC samples is weak and focal and had no relationship with the Gleason scores and Gleason grade groups. However, Ck-19 expression in PAC was high and was associated with tumor dedifferentiation of samples. There was no relationship between the expression of both markers with the patient's age.

Detection of CYFRA 21-1 in human serum by an electrochemical immunosensor based on UiO-66-NH2@CMWCNTs and CS@AuNPs.

In this study, an electrochemical immunosensor was constructed to detect the cytokeratin 19 fragment antigen 21-1 (CYFRA 21-1) in human serum. CYFRA 21-1 is the most sensitive tumor marker of non-small cell lung cancer (NSCLC), its content in normal human serum should be less than 3.3 ng/mL. When lung cancer cells dissolve or die, a myriad of CYFRA 21-1 is released into a tumor patient's blood circulation, and its serum content elevates strikingly. Consequently, detecting CYFRA 21-1 by an electrochemical biosensor is expected to provide a new method for the early detection and prevention of lung cancer. In this study, a composite of UiO-66-NH2 and carboxylated multi-walled carbon nanotubes (CMWCNTs) was used as the substrate material of a sensor; the resulting sensor had a large specific surface area and strong electrical conductivity. Moreover, gold nanoparticles (AuNPs) were used to bind to antibodies through an Au-S bonds. Also, a supersensitive detection of CYFRA 21-1 was achieved through the specific bindings of antigens and antibodies. Under optimal detection conditions, the change of current signal intensity of the immunosensor was proportional to the logarithm of CYFRA 21-1 concentration and had a linear relation in the range of 0.005-400 ng/mL, while the detection limit was 1.15 pg/mL (S/N = 3). The proposed immunosensor had high precision, stability, and selectivity. More importantly, the sensor was been successfully applied to detect CYFRA 21-1 in human serum with high recovery, providing a new method for early screening and dynamic monitoring of lung cancer.

Role of Serum CYFRA 21-1 in Diagnosis and Prognostic in Colorectal Liver Metastases.

Purpose: In current studies, the role of serum Cytokeratin-19 fragments (CYFRA 21-1) in colorectal cancer (CRC) remains unclear. This study aimed to clarify the diagnostic and prognostic value of CYFRA 21-1 in CRC. Patients and Methods: Data were collected for 196 stage I-III CRC patients and 50 colorectal liver metastases (CRLM) patients between January 2018 and December 2019. The serum CYFRA 21-1 levels were measured using the chemiluminescent particle immunoassay (CMIA) kit in all objects and common biomarkers such as CA19-9, CEA, HSP90α, and AFP were measured in all colorectal cancer patients. We investigated the association between CYFRA 21-1 level and clinicopathological features. In addition, we evaluated the ability of serum CRFRA21-1 to differentiate CRLM from CRC. To assess the potential prognostic value, we used Cox proportional hazard model for univariate or multivariate analyses. Results: Serum CYFRA 21-1 was significantly elevated in CRLM patients compared to stage I-III CRC patients (5.85 ng/mL vs 2.29 ng/mL, p < 0.001). For all CRC patients cohort, stage I-III CRC patients cohort and CRLM patients cohort, the optimal cutoff levels of CYFRA 21-1 for overall survival (OS) were 3.47 ng/mL, 2.14 ng/mL and 7.63 ng/mL, respectively, and the optimal cutoff levels for progression-free survival (PFS) were 3.47 ng/mL, 2.56 ng/mL and 7.63 ng/mL, respectively. For CRLM patients, Kaplan-Meier analysis showed that patients with high CYFRA 21-1 level had poor OS. Multivariate analysis indicated that the CYFRA 21-1 level was an independent prognostic factor for PFS in stage I-III patients. And CYFRA 21-1 levels and age were independent prognostic factors for OS and PFS in CRLM patients. Conclusion: CYFRA 21-1 can better differentiate CRLM patients from the whole CRC patients and has unique prognostic value for CRLM patients.

Clinical implications of Cytokeratin 19 expression in patients with oral squamous cell carcinoma.

Objective: This study was done to quantify the prevalence of high cytokeratin (CK) 19 expression in Indonesian oral squamous cell carcinoma (OSCC) patients and explore the prognostic role of CK19 in OSCC. Methods: Clinical data and samples from 61 patients diagnosed with OSCC at a tertiary national referral hospital in Jakarta, Indonesia were analyzed in this retrospective cohort study. Immunohistochemical staining of CK19 was performed on all patients and its expression was scored using the H system. All patients were followed up for a minimum of 36 months after diagnosis. Comparative and survival analyses were performed. Results: Twenty six point two percent of Indonesian OSCC patients had high CK19 expression. There were no differences in clinicopathological characteristics between patients with low and high CK19 expression. The 3-year overall survival (OS) of our cohort was 11.5%. Patients with high CK19 expression had lower 3-year OS compared to patients with low CK19 expression, even if the difference in OS was not statistically significant. Keratinization was an independent prognostic factor for survival in multivariate regression analysis. Conclusions: Data obtained here indicate a possible prognostic role of CK19 in OSCC. This prognostic role should be confirmed in larger series.

Stromal tissue segmentation in Ki67 histology images based on cytokeratin-19 stain translation.

Purpose: The diagnosis and prognosis of breast cancer relies on histopathology image analysis. In this context, proliferation markers, especially Ki67, are increasingly important. The diagnosis using these markers is based on the quantification of proliferation, which implies the counting of Ki67 positive and negative tumoral cells in epithelial regions, thus excluding stromal cells. However, stromal cells are often very difficult to distinguish from negative tumoral cells in Ki67 images and often lead to errors when automatic analysis is used. Approach: We study the use of automatic semantic segmentation based on convolutional neural networks (CNNs) to separate stromal and epithelial areas on Ki67 stained images. CNNs need to be accurately trained with extensive databases with associated ground truth. As such databases are not publicly available, we propose a method to produce them with minimal manual labelling effort. Inspired by the procedure used by pathologists, we have produced the database relying on knowledge transfer from cytokeratin-19 images to Ki67 using an image-to-image (I2I) translation network. Results: The automatically produced stroma masks are manually corrected and used to train a CNN that predicts very accurate stroma masks for unseen Ki67 images. An F-score value of 0.87 is achieved. Examples of effect on the KI67 score show the importance of the stroma segmentation. Conclusions: An I2I translation method has proved very useful for building ground-truth labeling in a task where manual labeling is unfeasible. With reduced correction effort, a dataset can be built to train neural networks for the difficult problem of separating epithelial regions from stroma in stained images where separation is very hard without additional information.

A radiomics nomogram for predicting cytokeratin 19-positive hepatocellular carcinoma: a two-center study.

Objectives: We aimed to construct and validate a radiomics-based nomogram model derived from gadoxetic acid-enhanced magnetic resonance (MR) images to predict cytokeratin (CK) 19-positive (+) hepatocellular carcinoma (HCC) and patients' prognosis. Methods: A two-center and time-independent cohort of 311 patients were retrospectively enrolled (training cohort, n = 168; internal validation cohort, n = 72; external validation cohort, n = 71). A total of 2286 radiomic features were extracted from multisequence MR images with the uAI Research Portal (uRP), and a radiomic feature model was established. A combined model was established by incorporating the clinic-radiological features and the fusion radiomics signature using logistic regression analysis. Receiver operating characteristic curve (ROC) was used to evaluate the predictive efficacy of these models. Kaplan-Meier survival analysis was used to assess 1-year and 2-year progression-free survival (PFS) and overall survival (OS) in the cohort. Results: By combining radiomic features extracted in DWI phase, arterial phase, venous and delay phase, the fusion radiomics signature achieved AUCs of 0.865, 0.824, and 0.781 in the training, internal, and external validation cohorts. The final combined clinic-radiological model showed higher AUC values in the three datasets compared with the fusion radiomics model. The nomogram based on the combined model showed satisfactory prediction performance in the training (C-index, 0.914), internal (C-index, 0.855), and external validation (C-index, 0.795) cohort. The 1-year and 2-year PFS and OS of the patients in the CK19+ group were 76% and 73%, and 78% and 68%, respectively. The 1-year and 2-year PFS and OS of the patients in the CK19-negative (-) group were 81% and 77%, and 80% and 74%, respectively. Kaplan-Meier survival analysis showed no significant differences in 1-year PFS and OS between the groups (P = 0.273 and 0.290), but it did show differences in 2-year PFS and OS between the groups (P = 0.032 and 0.040). Both PFS and OS were lower in CK19+ patients. Conclusion: The combined model based on clinic-radiological radiomics features can be used for predicting CK19+ HCC noninvasively to assist in the development of personalized treatment.

A Statistical Approach to the Diagnosis and Prediction of HCC Using CK19 and Glypican 3 Biomarkers.

Various statistical models predict the probability of developing hepatocellular carcinoma (HCC) in patients with cirrhosis, with GALAD being one of the most extensively studied scores. Biomarkers like alpha-fetoprotein (AFP), AFP-L3, and des-g-carboxyprothrombin (DCP) are widely used alone or in conjunction with ultrasound to screen for HCC. Our study aimed to compare the effectiveness of Cytokeratin 19 (CK19) and Glypican-3 (GPC3) as standalone biomarkers and in a statistical model to predict the likelihood of HCC. We conducted a monocentric prospective study involving 154 participants with previously diagnosed liver cirrhosis, divided into two groups: 95 patients with confirmed HCC based on clinical, biological, and imaging features and 59 patients without HCC. We measured the levels of AFP, AFP-L3, DCP, GPC3, and CK19 in both groups. We used univariate and multivariate statistical analyses to evaluate the ability of GPC3 and CK19 to predict the presence of HCC and incorporated them into a statistical model-the GALKA score-which was then compared to the GALAD score. AFP performed better than AFP-F3, DCP, GPC3, and CK19 in predicting the presence of HCC in our cohort. Additionally, GPC3 outperformed CK19. We used multivariate analysis to compute the GALKA score to predict the presence of HCC. Using these predictors, the following score was formulated: 0.005*AFP-L3 + 0.00069*AFP + 0.000066*GPC3 + 0.01*CK19 + 0.235*Serum Albumin-0.277. The optimal cutoff was >0.32 (AUROC = 0.98, sensitivity: 96.8%, specificity: 93%, positive predictive value-95.8%, negative predictive value-94.8%). The GALKA score had a similar predictive value to the GALAD score for the presence of HCC. In conclusion, AFP, AFP-L3, and DCP were the best biomarkers for predicting the likelihood of HCC. Our score performed well overall and was comparable to the GALAD score.

The added value of 18F-FDG PET/MRI multimodal imaging in hepatocellular carcinoma for identifying cytokeratin 19 status.

PURPOSE: In hepatocellular carcinoma (HCC), cytokeratin 19(CK19) has been proven to be associated with clinical aggressiveness. Therefore, this study aimed to explore the added value of 18F-FDG PET/MRI in predicting CK19 status in HCC. METHODS: Sixty-six patients who underwent whole-body or abdominal 18F-FDG PET/MRI after conventional PET/CT for HCC were retrospectively enrolled. The maximal standard uptake value (T-SUVmax) and the mean apparent diffusion coefficient (T-ADCmean) of the tumor (T), as well as those of the normal liver tissues (L) were derived, followed by calculations of the T-SUVmax/L-SUVmax (SUVmax-T/L) and the T-ADCmean/L-ADCmean (ADCmean-T/L) ratios. Combined with the postoperative pathological results, the performance in predicting the CK19 status in HCC was evaluated using receiver operating characteristic analysis (ROC). RESULTS: The areas under the ROC curve (AUCs) for T-SUVmax, SUVmax-T/L, T-ADCmean, and ADCmean-T/L in predicting the CK19-positive HCC were 0.700, 0.717, 0.717, and 0.735, respectively. In the logistic regression analysis, the T-SUVmax was an independent and significant factor to predict CK19-positive HCC, with an odds ratio of 1.27. In addition, no significant differences were found in the pathological grading, microvascular invasion, liver capsular invasion, Hepatitis B virus (HBV) infection, alpha fetoprotein (AFP) level, and tumor diameter between the CK19-positive and CK19-negative groups, except the recurrent rate. CONCLUSIONS: The radiomic features derived from 18F-FDG PET/MRI can be used to predict the CK19 status of HCC. T-SUVmax and T-ADCmean were significant indicators, whereas T-SUVmax was an independent predictor.