Keratin 19 (K19) is a cancer stem cell marker expressed by a subpopulation of hepatocellular carcinoma (HCC), associated with tumor aggressiveness. We evaluated the prognostic value of serum K19 fragment (CYFRA 21-1), in comparison or in combination with alpha-fetoprotein (AFP) and protein induced by vitamin-K absence or antagonist-II (PIVKA-II), in patients with HCC. A total of 160 patients (28F/132M; median age 62, range 44–86 years) with a new diagnosis of HCC and available serum samples collected at tumor diagnosis were analyzed retrospectively. Median overall survival (OS) after HCC diagnosis was 35.1, 95% CI 27.1–70.5 months. Multivariate Cox regression analysis showed that CYFRA 21-1 > 2.7 ng/mL (hazard ratio (HR) = 3.39, p < 0.001), AFP > 20 ng/mL (HR = 2.27, p = 0.007), and PIVKA-II > 200 mAU/mL (HR = 2.17, p = 0.020) were independent predictors of OS. The combination of biomarkers positivity allowed us to stratify patients with HCC into four risk categories associated with a progressively lower survival probability (log-rank test, p < 0.001). CYFRA 21-1 resulted an independent prognostic factor of patients with HCC and its combination with AFP and PIVKA-II might be useful to tailor personalized treatment strategies.

The COVID-19 pandemic has forced us to direct most of the available resources towards its management. This has led to the neglect of all other pathologies, including cancer. The aim of this study was to verify whether the difficulty in accessing the health system has led to a reduction in new diagnoses of hepatocellular carcinoma (HCC) and whether this has already been reflected in a more advanced stage of the cancer. A single-center, retrospective study including adult patients with a new diagnosis of HCC was performed. Patients were divided into three groups: the prelockdown phase (May 2019–February 2020), the lockdown phase (March 2020–December 2020), and the postlockdown phase (January 2021–October 2021); 247 patients were included. The number of patients diagnosed with HCC distinctly diminished in the periods March 2020–December 2020 (n = 69; −35%) and January 2021–October 2021 (n = 72; −32%) as compared to the period May 2019–February 2020 (n = 106). Noteworthy was the reduced surveillance in the period January 2021–October 2021 as compared to May 2019–February 2020 (22.9% vs. 36.6%, p = 0.056). No significant changes have yet been observed in tumor characteristics (BCLC staging distribution remained unvaried, p = 0.665). In conclusion, the number of new HCC diagnoses decreased sharply in the first 2 years of the pandemic, with no worsening of the stage. A more advanced stage of the disease could be expected in the next few years in patients who have escaped diagnosis.

This is a prospective and comparative study including 76 consecutive patients performing EUS-FNB for pancreatic and extrapancreatic solid lesions, randomized by alternate allocation to macroscopic on-site evaluation (MOSE) (40 patients) or to a conventional technique (40 patients), with three passes each. MOSE samples were differentiated into score 0: no visible material, score 1: only necrotic or haematic material, score 2: white core tissue ≤ 2 mm, or score 3: white core tissue > 2 mm. The conventional technique consisted in pushing all the needle content into a test tube for evaluation by the pathologist. In both groups, a 22–25 Gauge Franseen-tip needle (Acquire, Boston Scientific Co., Natick, MA, USA) was used. The study evaluated the diagnostic accuracy and adequacy of MOSE compared to the conventional technique and whether MOSE could optimize the number of passes during EUS-FNB. Results: The analysis was performed on 76 patients (38 MOSE, 38 conventional). The overall diagnostic adequacy was 94.7% (72/76) and accuracy was 84.2% (64/76). The diagnostic accuracy was similar in the two groups: MOSE 86.8% (33/38 lesions), vs. conventional 81.6%, 31/38 lesions, p = 0.76). Regarding diagnostic adequacy, the MOSE technique was 97.4% (111/114 passes) compared to 92.1% (105/114 passes) with the conventional technique, p = 0.06. The accuracy increased according to the MOSE score evaluation: it was 43.5%, 65.5% and 78.3% in patients with score 1, score 2, and score 3, respectively. Moreover, if in the first two passes the MOSE score was 2 or 3, the accuracy was 82.6% (20/23), and upon adding a third pass, the accuracy increased to 87% (20/23), which was not significantly different from the general accuracy of the MOSE samples (86.8%) (p = 0.86). Conclusions: The MOSE score showed a comparable diagnostic accuracy to the conventional technique. However, MOSE allows endoscopists to perform an inspective evaluation of the material, tends to perform better than the conventional technique in terms of diagnostic adequacy, and may potentially reduce the number of passes.

Background and aims: The identification of patients with Hepatitis C Virus (HCV)-positive advanced chronic liver disease (aCLD) successfully treated by Direct Acting Antiviral Agents (DAAs) who really benefit from Hepatocellular Carcinoma (HCC) surveillance programs is still a matter of debate. We performed a long-term prospective cohort study on F3-F4 HCV-positive patients achieving Sustained Virologic Response (SVR) after DAAs treatment in order to identify patients who can safely suspend surveillance. Methods: 1000 patients with HCV-positive aCLD obtaining SVR by DAAs from January 2015 to December 2017 were divided into four groups according to baseline elastographic, ultrasonographic, clinical and biochemical features: (1) Group 1: 324 patients with Liver Stiffness Measurement (LSM) ≥ 9.5 ≤ 14.5 kPa, FIB-4 < 3.25 and APRI < 1.5 (2) Group 2: 133 patients with LSM ≥ 9.5 ≤ 14.5 kPa, FIB-4 ≥ 3.25 and/or APRI ≥ 1.5 (3) Group 3: 158 patients with LSM > 14.5 kPa, FIB-4 < 3.25 and APRI < 1.5 (4) Group 4: 385 patients with LSM > 14.5 kPa, FIB-4 ≥ 3.25 and/or APRI ≥ 1.5. FIB-4 and APRI scores were calculated at baseline and at SVR achievement. Each patient was surveiled twice-yearly by ultrasound for a median follow-up of 48 months. Results: among Group 1 patients, 1/324 (0.3%) developed HCC (0.09/100 patients/year [PY]), compared to 6/133 (4.5%) Group 2 patients (1.22/100 PY, p = 0.0009), 10/158 (6.3%) Group 3 patients (1.68/100 PY, p = 0.0001), 54/385 (14.0%) Group 4 patients (4.01/100 PY, p < 0.0001). HCC incidence was significantly lower in Group 2 compared to Group 3 (p = 0.004) and in Group 3 compared to Group 4 (p = 0.009). HCC risk fell in patients showing a decrease of FIB-4/APRI scores. Conclusions: the risk of HCC occurrence is negligible in about 90% of HCV-positive patients with baseline LSM ≥ 9.5 ≤ 14.5 kPa plus FIB-4 < 3.25 and APRI < 1.5 achieving SVR. Among this particular subset of patients, FIB-4/APRI scores may represent an accurate and inexpensive tool to distinguish patients not needing long-term HCC surveillance.