Impact of multiple primary cancers on overall survival of patients with hepatocellular carcinoma.

The increasing occurrence of multiple primary cancers (MPC) is a long-term trend, but the prevalence of MPC in patients with hepatocellular carcinoma (HCC) and its impact on overall survival (OS) remains unknown. We retrospectively analyzed 497 patients with HCC treated at two tertiary centers. The cohort was divided into two subgroups - liver transplant (LT, 324 patients) and non-liver transplant (non-LT, 173 patients). We analyzed MPC occurrence, its impact on survival, and identified variables predicting unfavorable outcomes. The MPC were detected in 88 patients (18%). The most common MPC were prostate (17%), skin (15.9%), kidney (12.5%), and lung (10.2%). The median OS of the whole cohort and the LT and non-LT subgroups were 70, 116, and 17 months, respectively (p<0.0001). The median OS in patients with HCC only and HCC with another cancer was 77 (95% CI, 67-96) and 50 months (95% CI, 37-62), respectively (p=0.25). The OS of LT patients was significantly better than that of those in whom LT had been contraindicated owing to concomitant MPC (116 vs. 35 months, p<0.0009). Autoimmune etiology, non-alcoholic steatohepatitis (NASH), HCC as the first diagnosed malignancy, and male sex were identified as factors significantly influencing the patients' outcomes (HR 0.43, 3.2326, 0.70, and 1.43, respectively). The MPC frequency was 18%. The impact of MPC on OS was not significant, except for individuals contraindicated for LT because of MPC. A better prognosis is associated with the autoimmune etiology of cirrhosis, and when HCC is diagnosed as the first malignancy. Male sex and NASH worsened the outcomes.

Untargeted metabolomics of blood plasma samples of patients with hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths in the world. HCC is often diagnosed late because patients with early-stage cancer have no apparent symptoms. Therefore, it is desirable to find a reliable method for an early diagnosis based on the detection of metabolites - biomarkers, that can be detected in the early stages of the disease. Untargeted metabolomics is often used as a tool to find a suitable biomarker for several diseases. In this work, untargeted metabolomics was performed on blood plasma samples of HCC patients and compared with healthy individuals and patients with liver cirrhosis. A combination of liquid chromatography and high-resolution mass spectrometry was used as an analytical method. More than a thousand peaks were detected in the blood plasma samples, from which mainly amino acids, carboxylic acids, lipids, and their derivatives were evaluated as potential biomarkers. The data obtained were statistically processed using the analysis of variance, correlation analysis, and principal component analysis.

Efficacy of blood plasma spectroscopy for early liver cancer diagnostics in obese patients.

INTRODUCTION AND OBJECTIVES: Hepatocellular carcinoma (HCC) represents one of the most common cancers worldwide. A considerable proportion of HCC is caused by cirrhosis related to metabolic dysfunction-associated steatohepatitis (MASH). Due to the increasing prevalence of metabolic syndrome, it is estimated that MASH-related HCC will become the most prevalent etiology of HCC. Currently, HCC screening is based on liver ultrasonography; however, the sensitivity of ultrasonography for early HCC stages in obese patients only reaches 23 %. To date, no studied biomarker shows sufficient efficacy for screening purposes. Nevertheless, the usage of spectroscopic methods offers a new perspective, as its potential use would provide cheap, fast analysis of samples such as blood plasma. MATERIAL AND METHODS: We employed a combination of conventional and chiroptical spectroscopic methods to study differences between the blood plasma of obese cirrhotic patients with and without HCC. We included 20 subjects with HCC and 17 without evidence of liver cancer, all of them with body mass index ≥ 30. RESULTS: Sensitivities and specificities reached values as follows: 0.780 and 0.905 for infrared spectroscopy, 0.700 and 0.767 for Raman spectroscopy, 0.840 and 0.743 for electronic circular dichroism, and 0.805 and 0.923 for Raman optical activity. The final combined classification model based on all spectroscopic methods reached a sensitivity of 0.810 and a specificity of 0.857, with the highest area under the receiver operating characteristic curve among all models (0.961). CONCLUSIONS: We suggest that this approach can be used effectively as a diagnostic tool in patients who are not examinable by liver ultrasonography. CLINICAL TRIAL REGISTRATION: NCT04221347.

Comprehensive spectroscopic, metabolomic, and proteomic liquid biopsy in the diagnostics of hepatocellular carcinoma.

Liquid biopsy is a very topical issue in clinical diagnostics research nowadays. In this study, we explored and compared various analytical approaches to blood plasma analysis. Finally, we proposed a comprehensive procedure, which, thanks to the utilization of multiple analytical techniques, allowed the targeting of various biomolecules in blood plasma reflecting diverse biological processes underlying disease development. The potential of such an approach, combining proteomics, metabolomics, and vibrational spectroscopy along with preceding blood plasma fractionation, was demonstrated on blood plasma samples of patients suffering from hepatocellular carcinoma in cirrhotic terrain (n = 20) and control subjects with liver cirrhosis (n = 20) as well as healthy subjects (n = 20). Most of the applied methods allowed the classification of the samples with an accuracy exceeding 80.0 % and therefore have the potential to be used as a stand-alone method in clinical diagnostics. Moreover, a final panel of 48 variables obtained by a combination of the utilized analytical methods enabled the discrimination of the hepatocellular carcinoma samples from cirrhosis with 94.3 % cross-validated accuracy. Thus, this study, although limited by the cohort size, clearly demonstrated the benefit of the multimethod approach in clinical diagnosis.

Invasive measurement of hepatic venous pressure gradient before resection of hepatocellular carcinoma.

Aim of the study: To evaluate the role of hepatic venous pressure gradient (HVPG) measurement in patients with resectable hepatocellular carcinoma (HCC) we describe our experience with the procedure as part of our hospital standard preoperative algorithm. We present our protocol for this situation, the HVPG measurement procedure, and the results of our cohort. Material and methods: We performed a retrospective statistical analysis of all patients who underwent planned hepatic resection for HCC with HVPG measurement between 1/2016 and 1/2023. The cohort included 35 patients (30 males, mean age 69.5 years) who underwent HVPG measurement before liver resection for HCC. Results: The success rate of measurement was 91.4%, with serious complications in 2.9% of cases. Due to the clinically significant portal hypertension (CSPH) 31.3% of patients were rejected for resection. Seventeen patients with excluded CSPH underwent resection with one case of a postoperative liver event, liver decompensation, representing 5.9% of them. One patient (5.9%) had a complicated postoperative course with fasciitis. None of the patients who underwent resection (88.2%) was readmitted to the hospital due to surgical complications or a liver event during 90 days of follow-up, and no death was reported. The median overall survival (OS) in the resected subgroup was 70 months (95% CI: 52-86), and in patients rejected for surgery (resection and transplantation) 35 months (95% CI: 13-48). Conclusions: HVPG measurement is the gold standard for the quantification of portal hypertension. Hepatic vein catheterization is invasive, but a safe procedure, with a clear impact on the management of resectable HCC.

Acute pancreatitis - predicting the severity of the disease.

RATIONALE: Acute pancreatitis (AP) is a serious acute abdominal disease. AP is often referred to as an unpredictable illness, which can take a mild to severe (fatal) course. AIMS OF THE STUDY: 1) To identify clinical parameters that are significantly related to the clinical course of acute pancreatitis. 2) To compile a scoring system enabling the severity of AP to be predicted when the patient is first admitted to hospital. METHODS: Analysis of available publications and clinical guidance, and retrospective analysis of data on patients hospitalised with AP at our clinic enable us to identify clinical details and laboratory results recorded at the time of patients' admission to hospital that are related to the subsequent severity of the disease. For the purposes of statistical analysis, the sample of patients was divided into two groups: group A (mild AP, without local or organ complications), group B (moderately severe and severe AP with local and/or organ complications). PATIENT GROUPS AND RESULTS: In total, between 01.01.2013 and 30.06.2022, 312 patients with acute pancreatitis were allocated to the retrospective-prospective study sample. 74 % (231/312) of these patients were allocated to group A and 26 % (81/312) were allocated to group B. Univariate analysis of the data collected on the patient sample identified 5 parameters that are statistically significantly associated with the severity of the clinical course of the disease. Presence of SIRS on admission (A vs B, Odds ratio 10.787, 95% CI 5.09-22.85, p < 0.0001), diabetes mellitus type 2 in case history (A vs B, Odds ratio 7.703, 95% CI 3.04-19.51, p 2 mmol/l (A vs B, Odds ratio 3.293, 95% CI 1.59-6.82, p = 0.0013).In order to develop a scoring system, each of these parameters was allocated a points value based on its Odds ratio (OR): presence of SIRS 3 points, hypocalcaemia 3 points, diabetes mellitus type 2 in case history 2 points, urea concentration > 8 mmol/l 1 point and lactate concentration > 2 mmol/l 1 point. The authors refer to their scoring system as The Acute Pancreatitis Admission Score (APAS). The accuracy of APAS was modelled for various cut off values. Across the whole sample, we ascertained that an APAS ≥ 4 points predicts moderately severe or severe AP with a sensitivity of 81 % (95% CI: 71 - 89 %) and specificity of 87 % (95 CI: 81 - 91 %). The positive predictive value (PPV) of APAS ≥ 4 is 0.68, while its negative predictive value (NPV) is 0.93 and accuracy 0.85 (95% CI 0.81 - 0.89). CONCLUSION: In this study we identify significant simple clinical and laboratory parameters that are commonly tested as part of an initial examination when admitting a patient with AP to hospital. Having identified these parameters we are able to establish a simple scoring system that is able to predict the severity of the course of AP at the moment of hospitalisation (Tab. 5, Fig. 2, Ref. 27).

Hepatocellular carcinoma, multiple primary neoplasia, and their association with diabetes type 2.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and a frequent fatal complication of chronic liver diseases in the stage of liver cirrhosis. HCC develops at a higher rate in patients with type 2 diabetes mellitus (DM2). DM2 is associated with an increased risk of developing malignant tumors. The term multiple primary neoplasia (MPN) is used to describe the occurrence of multiple primary tumors of different organs in the same individual. To the best of the authors knowledge, the topic of the association between HCC and MPN and DM2 has not been addressed in the Czech literature. Here we present the outcomes of retrospective statistical analysis of a cohort of patients with HCC who were dispensed at the Internal Medicine Clinic of the 1st Faculty of Medicine of the Charles University in the period 2011-2021 and the impact of DM2 and MPN on overall survival (OS). MPNs are relatively common in patients with HCC. The occurrence of MPNs in our cohort was associated with DM2 in half of the cases. Median OS in HCC patients was not significantly affected by the coincidence of DM2 and/or MPNs.

Vibrational and chiroptical analysis of blood plasma for hepatocellular carcinoma diagnostics.

More than one fifth of the world's population suffers from liver cirrhosis or other chronic liver diseases. Unfortunately, some of them will inevitably develop hepatocellular carcinoma (HCC), due to the vast majority of HCC cases arising against the background of liver cirrhosis. Despite this clearly identified high-risk group, the lack of early diagnostic options causes HCC mortality to approach its incidence. As opposed to many types of cancer, the incidence of HCC is expected to grow in the coming decades, which makes the search for an effective early diagnostic option a pressing necessity. This study presents evidence that blood plasma analysis employing a combination of chiroptical and vibrational spectroscopic methods might be the key to the improvement of the current status. One hundred samples of patients with HCC and controls with cirrhosis were classified using principal component analysis together with a random forest algorithm. Differentiation of the specific spectral patterns of the studied groups was successful in more than 80%, indicating the prospect of including spectroscopy in the screening of high-risk groups, such as patients with cirrhosis.

Etiopathogenetic Factors of Hepatocellular Carcinoma, Overall Survival, and Their Evolution over Time-Czech Tertiary Center Overview.

Background and Objectives: Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer with a highly unfavorable prognosis. Aims: Retrospective statistical analysis of patients with HCC in the field of liver cirrhosis treated at our center from the perspective of demography, and the effects of key changes in diagnostic and therapeutic procedures in the last 10 years on overall survival (OS) and earlier diagnosis. Materials and Methods: This study included 170 cirrhotic patients with HCC (136 men, 80%). Demographic and etiological factors and OS were analyzed based on distribution into three groups according to the period and key changes in diagnostic and therapeutic approaches (BCLC classification staging; standardization of protocol for transarterial chemoembolization (TACE) and the introduction of direct-acting antivirals (DAA) for the treatment of chronic viral hepatitis C (HCV); expansion of systemic oncological therapy). Results: The mean age at the time of diagnosis was 69.3 years (SD = 8.1), and etiology was as follows: non-alcoholic steatohepatitis (NASH) 39%, alcoholic liver disease (ALD) 36%, HCV 18%, cryptogenic liver cirrhosis 3%, chronic hepatitis B infection (HBV) 2%, and other etiology 2%. Distribution of stages according to the BCLC: 0 + A 36%, B 31%, C 22%, and D 11%. However, the distribution in the first studied period was as follows: 0 + A 15%, B 34%, C 36%, and D 15%; and in the last period: 0 + A 45%, B 27%, C 17%, and D 11%, and difference was statistically significant (p < 0.05). The median OS for stages 0 + A, B, C, and D was 58, 19, 6, and 2 months, respectively. During the monitored period, there was a visible increase in the etiology of ALD from 30% to 47% and a decrease in HCV from 22% to 11%. In patients treated with TACE (stage B), the median OS grew from 10 to 24 months (p < 0.0001) between the marginal monitored periods. Conclusions: We described a decreasing number of patients with HCV-related HCC during follow-up possibly linked with the introduction of DAA. In our cohort, an improvement in early-stage diagnosis was found, which we mainly concluded as a result of proper ultrasound surveillance, the institution of a HCV treatment center, and increased experience of our sonographers with an examination of cirrhotic patients. Lastly, we described significantly improved overall survival in patients with intermediate HCC treated by TACE, due to the increased experience of interventional radiologists with the method at our facility and an earlier switch to systemic therapy in case of non-response to TACE.