Portal vein infiltration in patients with hepatocellular carcinoma: The relevance of correct classification.

e15651 Background: Portal vein invasion (PVI) is has a significant impact on the prognosis of patients with hepatocellular carcinoma (HCC). Patients with PVI are classified as stage C in the BCLC score and systemic therapy is recommended. Patients with minor PVI are frequently misclassified due to radiological challenges in determining malignant PVI or non-adherence to guidelines. The concept of resection or TACE in limited PVI is sometimes followed with the assumption of a negligible influence on survival. Aim of this study is the reevaluation of PVI and the analysis of the impact of a misclassification. Methods: 763 patients with HCC of a total of 1413 were extracted from the clinical registry of our tertiary center as an ongoing effort to reevaluate the extent of PVI in all patients treated between 1/1/2000 and 12/31/2015. PVI was diagnosed by re-evaluating all available CT or MRI scans by an experienced liver imaging radiologist. PVI was documented using the Liver Cancer Study Group of Japan classification ranging from Vp0-Vp4: Vp0 = no PVI; Vp1 = segmental; Vp2 = right anterior or posterior PV; Vp3 = right or left PV; Vp4 = main trunk. The influence on survival was calculated for each BCLC stage. Results: 259 patients (pat) were classified with PVI. Median age at diagnosis was 65.3 years, 213 patients (82.2%) were male. Etiology of liver disease was alcohol (43.6%), viral hepatitis (29.8%), NASH (5.8%), and others (10.4%). No liver disease was present in 18 pat (6.9%). No liver cirrhosis (LCI) was present in 32 pat (12.4%). LCI was classified as Child Pugh stage A/B/C in 65 (25.1%)/109 (42.1%) and 52 (20.1%) of patients. BCLC classification prior to reevaluation in pat with new PVI was A/B/C/D in 9/13/164/71 of cases. Comparing the overall survival (OS) of pat initially classified as BCLC A with or without PVI was 21.3 months vs. 106.4 months (p = 0.001), in BCLC B the OS was 11.0 months vs. 37.7 months (p = 0.001). Conclusions: Even minor PVI leads to dismal prognosis. Meticulous evaluation of cross sectional imaging is crucial for the clinical management of patients with HCC. Once PVI has been diagnosed, such patients have to be classified as advanced stage. The guidelines should be followed closely, irrespective of the extent of PVI.

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The impact of portal vein tumor thrombosis on survival in patients with hepatocellular carcinoma treated with different therapies: A cohort study

PLoS ONE ◽

10.1371/journal.pone.0249426 ◽

2021 ◽

Vol 16 (5) ◽

pp. e0249426

Author(s):

Aline Mähringer-Kunz ◽

Verena Steinle ◽

Roman Kloeckner ◽

Sebastian Schotten ◽

Felix Hahn ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cancer ◽

Portal Vein ◽

Systemic Therapy ◽

Cox Regression ◽

Portal Vein Tumor Thrombosis ◽

Main Trunk ◽

Cox Regression Analysis ◽

Tumor Thrombosis ◽

The Impact

Background Portal vein tumor thrombosis (PVTT) is a frequent complication of hepatocellular carcinoma (HCC), which leads to classification as advanced stage disease (regardless of the degree of PVTT) according to the Barcelona Clinic Liver Cancer Classification. For such patients, systemic therapy is the standard of care. However, in clinical reality, many patients with PVTT undergo different treatments, such as resection, transarterial chemoembolization (TACE), selective internal radiation therapy (SIRT), or best supportive care (BSC). Here we examined whether patients benefited from such alternative therapies, according to the extent of PVTT. Methods This analysis included therapy-naïve patients with HCC and PVTT treated between January 2005 and December 2016. PVTT was classified according to the Liver Cancer study group of Japan as follows: Vp1 = segmental PV invasion; Vp2 = right anterior or posterior PV; Vp3 = right or left PV; Vp4 = main trunk. Overall survival (OS) was analyzed for each treatment subgroup considering the extent of PVTT. We performed Cox regression analysis with adjustment for possible confounders. To further attenuate selection bias, we applied propensity score weighting using the inverse probability of treatment weights. Results A total of 278 treatment-naïve patients with HCC and PVTT were included for analysis. The median observed OS in months for each treatment modality (resection, TACE/SIRT, sorafenib, BSC, respectively) was 32.4, 8.1, N/A, and 1.7 for Vp1; 10.7, 6.9, 5.5, and 1.2 for Vp2; 6.6, 7.5, 2.9, and 0.6 for Vp3; and 8.0, 3.6, 5.3, and 0.7 for Vp4. Thus, the median OS in the resection group in case of segmental PVTT (Vp1) was significantly longer compared to any other treatment group (all p values <0.01). Conclusions Treatment strategy for HCC with PVTT should not be limited to systemic therapy in general. The extent of PVTT should be considered when deciding on treatment alternatives. In patients with segmental PVTT (Vp1), resection should be evaluated.

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Mechanisms of liver damage in COVID-19

Medical alphabet ◽

10.33667/2078-5631-2020-19-39-46 ◽

2020 ◽

Vol 1 (19) ◽

pp. 39-46

Author(s):

T. V. Pinchuk ◽

N. V. Orlova ◽

T. G. Suranova ◽

T. I. Bonkalo

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Transplantation ◽

Risk Factor ◽

Liver Disease ◽

Liver Function ◽

Liver Damage ◽

The World ◽

Coronavirus Infection ◽

The Impact ◽

Analyze Data

At the end of 2019, a new coronavirus (SARS-CoV-2) was discovered in China, causing the coronavirus infection COVID-19. The ongoing COVID-19 pandemic poses a major challenge to health systems around the world. There is still little information on how infection affects liver function and the significance of pre-existing liver disease as a risk factor for infection and severe COVID-19. In addition, some drugs used to treat the new coronavirus infection are hepatotoxic. In this article, we analyze data on the impact of COVID-19 on liver function, as well as on the course and outcome of COVID-19 in patients with liver disease, including hepatocellular carcinoma, or those on immunosuppressive therapy after liver transplantation.

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The impact of COVID-19 pandemic on training and mental health of residents: a cross-sectional study

BMC Medical Education ◽

10.1186/s12909-021-02655-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Eman Alshdaifat ◽

Amer Sindiani ◽

Wasim Khasawneh ◽

Omar Abu-Azzam ◽

Aref Qarqash ◽

...

Keyword(s):

Mental Health ◽

Residency Training ◽

Training Programs ◽

Cross Sectional Study ◽

Protective Equipment ◽

Sectional Study ◽

Cross Sectional ◽

Surgical Residents ◽

Tertiary Center ◽

The Impact

Abstract Background Residency programs have been impacted by the Coronavirus disease 2019 (COVID-19) pandemic. In this study we aim to investigate and evaluate the impact of the pandemic on residents as well as residency training programs. Methods This was a cross-sectional study including a survey of 43 questions prepared on Google forms and electronically distributed among a convenience sample of residents training at a tertiary center in North Jordan during the COVID-19 pandemic. Data were collected in the period between October 30th and November 8th of 2020. The survey included questions that addressed the impact of the pandemic on residents’ health as well as training programs. The study participants included residents in training at KAUH in 2020 and were stratified according to the type of residency program (surgical residents (SRs) and non-surgical residents (NSRs)). Statistical methods included descriptive analysis, Chi-square or Fisher’s exact test, Mann Whitney U test, and Cramer’s V and r statistics as measures of effect sizes. Results Of all 430 residents, 255 (59%) responded to the survey. A total of 17 (7%) of residents reported being infected with COVID-19 and a significant difference was reported between SRs and NSRs (10% vs 4%, V = .124 “small effect” (95% CI; .017–.229), p = 0.048). Approximately, 106 (42%) reported a decrease in the number of staff working at the clinic and 164 (64%) reported limited access to personal protective equipment during the pandemic. On a 4-point Likert scale for the feeling of anxiety, the median was 2 (2–3 IQR) in the NSRs group, vs 2 (1–2 IQR) in the SRs groups, with the NSRs being more likely to feel anxious (r = 0.13 “small effect” (95% CI; 0.007–0.249), p = .044). Similarly, the proportion of residents who reported feeling anxious about an inadequacy of protective equipment in the work area was significantly greater in the NSRs group (90.3% vs 75.2%; V = .201 “small effect” (95% CI; .078–.313), p = .001), as well as the proportion of residents who reported feeling increased stress and anxiety between colleagues being also significantly higher in the NSRs group (88.1% vs 76%; V = .158 “small effect” (95% CI; .032–.279), p = .012). Conclusion The burden of the ongoing pandemic on the mental health status of residents is very alarming and so providing residents with psychological counseling and support is needed. Also, critical implications on the flow of residency training programs have been noticed. This necessitates adapting and adopting smart educational techniques to compensate for such limitations.

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Two Metabolomics Phenotypes of Human Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease According to Fibrosis Severity

Metabolites ◽

10.3390/metabo11010054 ◽

2021 ◽

Vol 11 (1) ◽

pp. 54

Author(s):

Benjamin Buchard ◽

Camille Teilhet ◽

Natali Abeywickrama Samarakoon ◽

Sylvie Massoulier ◽

Juliette Joubert-Zakeyh ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Monounsaturated Fatty Acids ◽

Metabolic Reprogramming ◽

Resonance Spectroscopy ◽

Alcoholic Fatty Liver ◽

The Impact ◽

Alcoholic Fatty Liver Disease

Non-Alcoholic Fatty Liver Disease (NAFLD) is considered as the forthcoming predominant cause for hepatocellular carcinoma (HCC). NAFLD-HCC may rise in non-cirrhotic livers in 40 to 50% of patients. The aim of this study was to identify different metabolic pathways of HCC according to fibrosis level (F0F1 vs. F3F4). A non-targeted metabolomics strategy was applied. We analyzed 52 pairs of human HCC and adjacent non-tumoral tissues which included 26 HCC developed in severe fibrosis or cirrhosis (F3F4) and 26 in no or mild fibrosis (F0F1). Tissue extracts were analyzed using 1H-Nuclear Magnetic Resonance spectroscopy. An optimization evolutionary method based on genetic algorithm was used to identify discriminant metabolites. We identified 34 metabolites differentiating the two groups of NAFLD-HCC according to fibrosis level, allowing us to propose two metabolomics phenotypes of NAFLD-HCC. We showed that HCC-F0F1 mainly overexpressed choline derivatives and glutamine, whereas HCC-F3F4 were characterized by a decreased content of monounsaturated fatty acids (FA), an increase of saturated FA and an accumulation of branched amino acids. Comparing HCC-F0F1 and HCC-F3F4, differential expression levels of glucose, choline derivatives and phosphoethanolamine, monounsaturated FA, triacylglycerides were identified as specific signatures. Our metabolomics analysis of HCC tissues revealed for the first time two phenotypes of HCC developed in NAFLD according to fibrosis level. This study highlighted the impact of the underlying liver disease on metabolic reprogramming of the tumor.

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Hepatocellular carcinoma: Intratumoral EpCAM-positive cancer stem cell heterogeneity identifies high-risk tumor subtype

10.21203/rs.3.rs-54971/v3 ◽

2020 ◽

Author(s):

Jenny Krause ◽

Johann von Felden ◽

Christian Casar ◽

Thorben W. Fründt ◽

Johanna Galaski ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

High Risk ◽

Spatial Heterogeneity ◽

Early Recurrence ◽

Epcam Expression ◽

Clinical Endpoints ◽

Time To Recurrence ◽

Dismal Prognosis ◽

The Impact ◽

Intratumoral Distribution

Abstract Background: The translational interest in the intratumoral heterogeneity of hepatocellular carcinoma (HCC) has been increasing. The dismal prognosis of this pathology is linked to the features of the HCC harbouring cancer stem cells (CSC), represented by EpCAM-expression. However, the extent of the impact of intratumoral distribution of CSC-features, both on the recurrence after curative resection and on clinical outcome, remains unknown. To address this, we investigated the spatial heterogeneity of CSC-features with the aim of identifying the unique HCC patient subgroups amenable to adjuvant treatment.Methods: We designed a tissue microarray (TMA) from patients who had received liver resection between 2011 and 2017. Tumor specimens were sampled at multiple locations (n=3-8). EpCAM-positivity was assessed for intensity and proportion by applying a score dividing three groups: (i) negative (E-/-); (ii) heterogeneous (E-/+); and (iii) homogeneous (E+/+). The groups were further analysed with regard to time-to-recurrence (TTR) and recurrence-free-survival (RFS).Results: We included 314 tumor spots from 69 patients (76.8% male, median age 66 years, liver cirrhosis/fibrosis 75.8). The risk factors were alcohol abuse (26.2%), NASH (13.1%), HBV (15.5%), HCV (17.9%) and others (27.4%), representative of a typical Western cohort. E+/+ patients experienced significantly shorter TTR and RFS compared to E+/- (and E-/-) patients (TTR 5 vs. 19 months, p=0.022; RFS 5 vs. 14 vs. 21 months, p=0.016). Only homogeneous EpCAM-positivity correlated with higher AFP levels (>400 ng/ml, p=0.031).Conclusions: Spatial heterogeneity of EpCAM-expression was markedly present in the cohort. Of note, only homogeneous EpCAM-expression correlated significantly with early recurrence, whereas heterogeneous EpCAM-expression was associated with clinical endpoints comparable to EpCAM-negativity. We identified a unique HCC subtype associated with a high risk of tumor recurrence.

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Liver Fibrosis is Associated with a Decrease in Gait Speed in Older Men with Chronic Liver Disease: A Retrospective Cross-Sectional Study

10.21203/rs.3.rs-819599/v1 ◽

2021 ◽

Author(s):

Kenichi Fudeyasu ◽

Takuo Nomura ◽

Toshihiro Kawae ◽

Daisuke Iwaki ◽

Yuki Nakashima ◽

...

Keyword(s):

Liver Disease ◽

Liver Fibrosis ◽

Chronic Liver Disease ◽

Motor Function ◽

Gait Speed ◽

Older Patients ◽

Knee Extension ◽

Chronic Liver ◽

Cross Sectional ◽

The Impact

Abstract Background: Although it has already been reported that chronic liver disease (CLD) can induce sarcopenia, the impact of sarcopenia, especially on motor function, in older patients with CLD is still unclear. Therefore, we investigated the effects of liver fibrosis on motor function in these patients.Methods: In all, 117 older patients with CLD aged above 60 years (men, n=70; women, n=47) were included in this study. We examined the presence or absence of sarcopenia and checked motor functions such as muscle strength and walking speed. The results were compared between patients with FIB-4 index of >3.25, indicative of severe-degree liver fibrosis (SLF), and those with an index of <3.25, indicative of low-degree liver fibrosis (LLF). We also analyzed the factors related to the decrease in gait speed.Results: The decrease in gait speed (<1.0 m/s) was significantly higher (P = 0.027) and the knee extension force (KEF) was significantly lower (P = 0.010) in men with SLF than in those with LLF. In this study, liver fibrosis (odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.56–0.90) and KEF (OR = 1.09, 95% CI = 1.02–1.16) were identified as factors associated with the decrease in gait speed.Conclusions: Older male patients with CLD have decreased motor function as the disease progresses. We found that the decrease in gait speed is related to liver fibrosis and KEF. It is necessary to focus on the motor function of older patients with CLD, especially the gait speed.

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Hepatocellular Carcinoma Is the Most Frequent Final Diagnosis of Focal Liver Lesions Identified in a Cross-Sectional Evaluation of Patients with Chronic Liver Disease in Saudi Arabia

Journal of Cancer Research ◽

10.1155/2015/492782 ◽

2015 ◽

Vol 2015 ◽

pp. 1-4 ◽

Cited By ~ 1

Author(s):

Adnan Agha ◽

Manuele Furnari ◽

Rafaat Morched Chakik ◽

Mamdouh M. Abdulhadi Ali ◽

Dib Alsaudi ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Disease ◽

Chronic Liver Disease ◽

Odds Ratio ◽

Final Diagnosis ◽

Liver Lesion ◽

Focal Liver Lesions ◽

Liver Lesions ◽

Benign Lesions ◽

Cross Sectional

Background. Hepatocellular carcinoma (HCC) is a frequent diagnosis in patients with chronic liver disease (CLD) and a newly identified liver lesion, although benign diseases may also be responsible for this finding. Objective. To evaluate the characteristics of focal liver lesions in a population of patients with CLD not under surveillance for HCC in the Middle East. Methods. We performed a cross-sectional study evaluating 77 patients with CLD and a focal liver lesion identified during ultrasonography. Patients’ characteristics were analyzed on the basis of the final diagnosis (HCC versus benign lesions). Results. The most frequent diagnosis was HCC (64.9%). These patients were older (median age 64 versus 55 years, P=0.003) and cirrhotics (80.0% versus 51.9%, P=0.018), with multinodular lesions (58.0% versus 29.6%, P=0.031) and portal vein thrombosis (24.0% versus 0%, P=0.001) compared to patients with benign lesions. Prevalence of elevated alpha-fetoprotein (>10 ng/mL) was similar in both groups (80.0% versus 88.9%, P=0.198). Cirrhosis (odds ratio: 3.283) and multinodularity (odds ratio: 2.898) were independently associated with HCC. Conclusions. HCC is the most common diagnosis in Middle-Eastern patients with CLD and a liver lesion identified outside HCC surveillance programs, especially in cirrhotic patients. In these patients, elevated alpha-fetoprotein does not differentiate HCC from benign lesions.

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Distant survival for patients undergoing surgery using volatile versus IV anesthesia for hepatocellular carcinoma with portal vein tumor thrombus: a retrospective study

BMC Anesthesiology ◽

10.1186/s12871-020-01111-w ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Xiao-Yan Meng ◽

Xiu-Ping Zhang ◽

Zhe Sun ◽

Hong-Qian Wang ◽

Wei-Feng Yu

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Portal Vein ◽

Tumor Thrombus ◽

Cox Regression ◽

Cancer Recurrence ◽

Portal Vein Tumor Thrombus ◽

Cox Regression Analysis ◽

The Impact ◽

Underlying Pathophysiology

Abstract Background Whether anesthesia type is associated with the surgical outcome of Hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) remains to be determined. This study aims to investigate the impact of volatile inhalational anesthesia (INHA) versus total IV anesthesia (TIVA) on the survival outcomes in HCC patients with PVTT. Methods A cohort of in-patients whom were diagnosed of HCC with PVTT in Eastern Hepatobiliary Surgery Hospital, Shanghai, China, from January 1, 2008 to December 24, 2012 were identified. Surgical patients receiving the INHA and TIVA were screened out. The overall survival (OS), recurrence-free survival (RFS) and several postoperative adverse events were compared according to anesthesia types. Results A total of 1513 patients were included in this study. After exclusions are applied, 263 patients remain in the INHA group and 208 in the TIVA group. Patients receiving INHA have a lower 5-year overall survival rate than that of patients receiving TIVA [12.6% (95% CI, 9.0 to 17.3) vs. 17.7% (95% CI, 11.3 to 20.8), P = 0.024]. Results of multivariable Cox-regression analysis also identify that INHA anesthesia is significantly associated with mortality and cancer recurrence after surgery compare to TIVA, with HR (95%CI) of 1.303 (1.065, 1.595) and 1.265 (1.040, 1.539), respectively. Subgroup analysis suggested that in more severe cancer patients, the worse outcome related to INHA might be more significant. Conclusion This retrospective analysis identifies that TIVA is associated with better outcomes compared with INHA. Future prospective studies clinical and translational studies are required to verify this difference and investigate underlying pathophysiology.

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