Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma: Real-life Data on Liver Disease, Treatment and Prognosis.

Background and Aims: Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) have common features and differences. This real-life study investigated their characteristics, treatment modalities, and prognoses. Methods: This retrospective comparative study was performed in 1,075 patients seen at one tertiary center between January 2008 and December 2020. Overall survival (OS) was estimated by the Kaplan-Meier method. Subclassification of iCCAs after histological and radiological review, and molecular profiling was performed. Results: HCCs patients were more likely to have early-stage disease than iCCA patients. iCCA patients were more likely to be female, especially those patients without cirrhosis (43% vs. 17%). Cirrhosis was prominent among HCC patients (89% vs. 34%), but no difference in underlying liver disease among cirrhotic patients was found. OS of HCC patients was 18.4 (95% CI: 6.4, 48.3) months, that of iCCA patients was 7.0 (95% CI: 3.4, 20.1) months. OS of Barcelona Clinic Liver Cancer C HCC patients was 7.8 (95% CI: 4.3, 14.2) months, that of advanced/metastatic iCCA patients was 8.5 (95% CI: 5.7, 12.3) months. In patients treated with sorafenib, OS was longer in HCC patients who received subsequent tyrosine kinase inhibitor therapies. No significant OS difference was found between iCCA patients with and without cirrhosis or according to histological subtype. A targetable molecular alteration was detected in 50% of the iCCA patients. Conclusions: In this French series, cirrhosis was common in iCCA, which showed etiological factors comparable to those of HCC, implying a distinct oncogenic pathway. Both entities had a dismal prognosis at advanced stages. However, systemic therapies sequencing in HCC and molecular profiling in iCCA offer new insights.

Multi-criterion, automated, high-performance, rapid tool for assessing mucosal visualization quality of still images in small bowel capsule endoscopy.

Background and study aims Capsule endoscopy (CE) is the preferred method for small bowel (SB) exploration. Its diagnostic yield can be reduced by poor mucosal visualization. We aimed to evaluate three electronic parameters - colorimetry, abundance of bubbles, and brightness - to assess the adequacy of mucosal visualization of SB-CE images. Patients and methods Six-hundred still images were randomly extracted from 30 complete and normal SB-CEs. Three experts independently evaluated these images according to a 10-point assessment grid. Any frame with a mean score above seven was considered adequately cleansed. Each image was analyzed electronically according to the three preset parameters, individually and then combined, with the experts' score as reference. A random forests methodology was used for machine learning and testing. Results The combination of the three electronic parameters achieved better discrimination of adequately from inadequately cleansed frames as compared to each individual parameter taken separately (sensitivity 90.0 % [95 %C. I. 84.1 - 95.9], specificity 87.7 % [95 %C. I. 81.3 - 94.2]). Conclusion This multi-criterion score constitutes a comprehensive, reproducible, reliable, automated and rapid cleansing score for SB-CE frames. A patent is pending at the European patent office.

Hepatocellular carcinoma macroscopic gross appearance on imaging: predictor of outcome after transarterial chemoembolization in a real-life multicenter French cohort.

BACKGROUND: Conventional transarterial chemoembolization (cTACE) with lipiodol is widely performed in patients with hepatocellular carcinoma (HCC) unsuitable for curative treatment. Additional tumor parameters such as HCC macroscopic appearance based on imaging might be helpful for transarterial chemoembolization prognostication and management. PATIENTS AND METHODS: A total of 405 patients with HCC who underwent cTACE between 2008 and 2016 from a real-life multicenter French cohort were retrospectively reviewed. Tumors were classified into two macroscopic types according to HCC gross appearance on imaging: nodular versus non-nodular. The study population was stratified into two groups: derivation and validation cohorts. Independent prognostic factors of survival based on multivariate cox regression models were determined and then assessed in the validation set. Thereafter, time to progression (TTP) and radiological response rate were investigated for each prognostic factors of survival. RESULTS: Median overall survival (OS) was 35 months for Barcelona Clinic Liver Cancer (BCLC) stage A, 22 months for BCLC stage B and 12 months for BCLC stage C patients (P < 0.0001). The corresponding TTP for these patients was 12 (7-17) months, 5 (3-6) months and 1.2 (1.2-3) months (P < 0.0001). Multivariate analysis revealed that tumors size and number, non-nodular type, alpha-fetoprotein, aspartate aminotransferase serum levels and impairment of performance status-1 were independent predictors of survival among the study groups. Non-nodular type was the most powerful factor that influences OS, TTP and radiological response rate for the recommended transarterial chemoembolization candidates. TTP was consistent with OS within each stage. CONCLUSION: HCC macroscopic appearance on imaging is a determinant predictor of outcome after cTACE in a real-life multicenter cohort.

Hepatitis C virus therapy: No one will be left behind.

The advent of oral direct-acting antiviral agents (DAAs) has dramatically improved the hepatitis C treatment landscape in the last 4 years, providing cure rates over 95% with shorter duration of treatment and a very good safety profile. This gave access to treatment to almost all Hepatitis C virus (HCV)-infected patients. The launch of two pangenotypic fixed-dose combinations (FDCs) in 2017 was a step forward in hepatitis C treatment, by slightly increasing efficacy and more importantly allowing the treatment of patients without HCV genotyping, and in some cases without fibrosis assessment. New triple regimens have solved the issue of retreatment of the few patients who present failure to DAAs therapy. In the present review we describe the current HCV landscape that allows almost all HCV-infected patients to be cured.

Sofosbuvir, velpatasvir and voxilaprevir: a new triple combination for hepatitis C virus treatment. One pill fits all? Is it the end of the road?

The advent of oral direct-acting antiviral agents (DAAs) has dramatically improved the hepatitis C virus (HCV) treatment landscape in the last 4 years, providing cure rates over 95% with a shorter duration of treatment and a very good safety profile. This has enabled access to treatment in nearly all HCV infected patients. The launch of two pangenotypic fixed dose combinations (FDCs) in 2017 made a new step forward in HCV treatment by slightly increasing efficacy and more importantly allowing the treatment of patients without HCV genotyping, and in some cases without fibrosis assessment. However, retreatment of the few DAA failure patients was still an issue for some HCV genotypes. The launch of the triple regimen FDC, sofosbuvir/velpatasvir/voxilaprevir, solves this issue by providing a cure rate over 96% regardless of HCV genotype. In this review, we describe the current HCV treatment landscape and focus on the development of this triple FDC either in treatment-naïve or treatment-experienced patients with previous failure on a DAA regimen.

Development of a computed cleansing score to assess quality of bowel preparation in colon capsule endoscopy.

BACKGROUND AND STUDY AIMS: Colon capsule endoscopy (CCE) does not possess an objective and reliable scoring system to assess the quality of visualization of the colon mucosa. The aim of this study was to establish a colonic computed assessment of cleansing (CAC) score able to discriminate "adequately cleansed" from "inadequately cleansed" CCE still frames. PATIENTS AND METHODS: Twelve normal and complete CCEs, using the Pillcam Colon 2 system (Medtronic, Minnesota, United States), were prospectively selected amongst a database. A CAC score, defined as the ratio of color intensities red over green (R/G ratio), and red over brown (R/(R + G) ratio) was calculated for each extracted colonic frame. After sorting and random selection, two sets of still frames representative of the range of these ratios were obtained. These images were analyzed twice in random order by two experienced CCE readers who were blinded to the CAC scores. A receiver operating characteristic (ROC) curve was forged for both types of ratios and a threshold established, yielding the highest diagnostic performance in terms of adequate cleansing assessment. RESULTS: Four-hundred-and-eight frames were extracted. Regarding the R/G ratio, a threshold value of 1.55 was calculated, with a sensitivity of 86.5 % and a specificity of 77.7 %. Regarding the R/(R + G) ratio, a threshold value of 0.58 was calculated with a sensitivity of 95.5 % and a specificity of 62.9 %. CONCLUSION: The two proposed CAC scores based on the ratio of color intensities come with high sensitivities for discriminating between "adequately cleansed" and "inadequately cleansed" CCE still frames, but they lack specificity. Further refinement, with implementation of additional image parameters, is warranted.

Development and validation of a computed assessment of cleansing score for evaluation of quality of small-bowel visualization in capsule endoscopy.

BACKGROUND AND STUDY AIMS: An objective and reliable scoring system is needed to assess quality of visualization in small bowel (SB) capsule endoscopy (CE), for both clinical practice and research purposes. The aim of this study was to establish and to validate a SB-computed assessment of cleansing (SB-CAC) score. PATIENTS AND METHODS: Thirty-three SB-CE were selected. A CAC score, defined as the ratio of the red over green pixels (R/G ratio), was calculated for each frame. Intervals were then determined, ranging from the lowest to the highest ratio among the extracted frames. Twelve frames were randomly selected in each of these intervals. Two hundred eighty-eight frames were shuffled and analyzed twice in random order by two experienced CE readers who were blinded to the CAC scores. Once an "adequately cleansed" or "inadequately cleansed" qualification was allotted to every still frame, a receiver operating characteristic (ROC) curve was created. In case of discrepancy between the two readers, the still frames were excluded. A second dataset of 288 different SB still frames was generated and read twice in random order by two other experienced SB-CE readers, using the same methodology. RESULTS: A SB-CAC score threshold of 1.6 best achieved discrimination of adequately from inadequately cleansed frames, with a sensitivity of 92.7 % (95 %CI [89.7 - 95.8]) and a specificity of 92.9 % (95 %CI [89.9 - 95.9]). This threshold was validated using the second dataset, yielding the following performances: sensitivity 91.3 % (95 %CI [87.9 - 94.6]), specificity 94.7 % (95 %CI [92.1 - 97.3]). CONCLUSION: An SB-CAC score of 1.6 has the highest sensitivity and specificity to discriminate "adequately cleansed" from "inadequately cleansed" SB-CE still frames. This constitutes an objective, reproducible, reliable, and automated cleansing score for SB-CE.

Development and validation of an automated algorithm to evaluate the abundance of bubbles in small bowel capsule endoscopy.

BACKGROUND AND STUDY AIMS: Bubbles can impair visualization of the small bowel (SB) mucosa during capsule endoscopy (CE). We aimed to develop and validate a computed algorithm that would allow evaluation of the abundance of bubbles in SB-CE still frames. PATIENTS AND METHODS: Two sets of 200 SB-CE normal still frames were created. Two experienced SB-CE readers analyzed both sets of images twice, in a random order. Each still frame was categorized as presenting with < 10 % or ≥ 10 % of bubbles. Reproducibility (κ), sensitivity (Se), specificity (Sp), receiver operating characteristic curve, and calculation time were measured for different algorithms (Grey-level of co-occurrence matrix [GLCM], fractal dimension, Hough transform, and speeded-up robust features [SURF]) using the experts' analysis as reference. Algorithms with highest reproducibility, Se and Sp were then selected for a validation step on the second set of frames. Criteria for validation were κ = 1, Se ≥ 90 %, Sp ≥ 85 %, and a calculation time < 1 second. RESULTS: Both SURF and GLCM algorithms had high operating points (Se and Sp over 90 %) and a perfect reproducibility (κ = 1). The validation step showed the GLCM detector strategy had the best diagnostic performances, with a Se of 95.79 %, a Sp of 95.19 %, and a calculation time of 0.037 seconds per frame. CONCLUSION: A computed algorithm based on a GLCM detector strategy had high diagnostic performance allowing assessment of the abundance of bubbles in SB-CE still frames. This algorithm could be of interest for clinical use (quality reporting) and for research purposes (objective comparison tool of different preparations).