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1.
Clin Mol Hepatol ; 27(4): 564-574, 2021 10.
Article in English | MEDLINE | ID: covidwho-1551487

ABSTRACT

BACKGROUND/AIMS: In July 2017, the Emprint™ next-generation microwave ablation system using thermosphere technology (Covidien, Boulder, CO, USA) was approved for use in Japan. This system can produce a predictable spherical ablation zone at higher temperatures than radiofrequency ablation (RFA). The aim of the present study was to elucidate whether this new microwave thermosphere ablation (MTA) could safely improve outcome compared to RFA, which is the standard of care for small hepatocellular carcinoma (HCC). METHODS: This retrospective study analyzed 513 patients with 630 HCCs (≤3 cm) who were performed by percutaneous RFA (174 patients, 214 HCCs) or MTA (339 patients, 416 HCCs) between January 2016 and March 2020. RESULTS: Median ablation time was significantly shorter for MTA (240 seconds) than for RFA (721 seconds; P<0.001). A significant difference in 3-year local tumor progression rate was evident between the RFA group (22%) and MTA group (8%; P<0.001). Multivariable analysis revealed ablation procedure and tumor diameter as independent factors contributing to local tumor progression (MTA; P<0.001; hazard ratio, 0.565; 95% confidence interval, 0.437-0.731). In patients with primary HCC, a significant difference in overall survival was evident (RFA vs. MTA, 3-year, 77% vs. 95%, P=0.029). Ablation procedure and Child-Pugh score were independent factors contributing to survival. The total complication rate was significantly lower for MTA (8%) than for RFA (14%, P<0.05), particularly for bile duct injury (3% vs. 9%, respectively; P<0.05). CONCLUSION: Next-generation MTA for small HCC could provide safer, more curative treatment in a shorter ablation time than RFA.


Subject(s)
Carcinoma, Hepatocellular , Catheter Ablation , Liver Neoplasms , Radiofrequency Ablation , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/surgery , Humans , Liver Neoplasms/diagnosis , Liver Neoplasms/surgery , Microwaves , Radiofrequency Ablation/adverse effects , Retrospective Studies , Treatment Outcome
2.
Clin Mol Hepatol ; 27(4): 564-574, 2021 10.
Article in English | MEDLINE | ID: covidwho-1456286

ABSTRACT

BACKGROUND/AIMS: In July 2017, the Emprint™ next-generation microwave ablation system using thermosphere technology (Covidien, Boulder, CO, USA) was approved for use in Japan. This system can produce a predictable spherical ablation zone at higher temperatures than radiofrequency ablation (RFA). The aim of the present study was to elucidate whether this new microwave thermosphere ablation (MTA) could safely improve outcome compared to RFA, which is the standard of care for small hepatocellular carcinoma (HCC). METHODS: This retrospective study analyzed 513 patients with 630 HCCs (≤3 cm) who were performed by percutaneous RFA (174 patients, 214 HCCs) or MTA (339 patients, 416 HCCs) between January 2016 and March 2020. RESULTS: Median ablation time was significantly shorter for MTA (240 seconds) than for RFA (721 seconds; P<0.001). A significant difference in 3-year local tumor progression rate was evident between the RFA group (22%) and MTA group (8%; P<0.001). Multivariable analysis revealed ablation procedure and tumor diameter as independent factors contributing to local tumor progression (MTA; P<0.001; hazard ratio, 0.565; 95% confidence interval, 0.437-0.731). In patients with primary HCC, a significant difference in overall survival was evident (RFA vs. MTA, 3-year, 77% vs. 95%, P=0.029). Ablation procedure and Child-Pugh score were independent factors contributing to survival. The total complication rate was significantly lower for MTA (8%) than for RFA (14%, P<0.05), particularly for bile duct injury (3% vs. 9%, respectively; P<0.05). CONCLUSION: Next-generation MTA for small HCC could provide safer, more curative treatment in a shorter ablation time than RFA.


Subject(s)
Carcinoma, Hepatocellular , Catheter Ablation , Liver Neoplasms , Radiofrequency Ablation , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/surgery , Humans , Liver Neoplasms/diagnosis , Liver Neoplasms/surgery , Microwaves , Radiofrequency Ablation/adverse effects , Retrospective Studies , Treatment Outcome
3.
PLoS One ; 16(8): e0256544, 2021.
Article in English | MEDLINE | ID: covidwho-1374151

ABSTRACT

BACKGROUND: Patients with hepatocellular carcinoma (HCC) represent a vulnerable population potentially negatively affected by COVID-19-associated reallocation of healthcare resources. Here, we report the impact of COVID-19 on the management of HCC patients in a large tertiary care hospital. METHODS: We retrospectively analyzed clinical data of HCC patients who presented at the Vienna General Hospital, between 01/DEC/2019 and 30/JUN/2020. We compared patient care before (period 1) and after (period 2) implementation of COVID-19-associated healthcare restrictions on 16/MAR/2020. RESULTS: Of 126 patients, majority was male (n = 104, 83%) with a mean age of 66±11 years. Half of patients (n = 57, 45%) had impaired liver function (Child-Pugh stage B/C) and 91 (72%) had intermediate-advanced stage HCC (BCLC B-D). New treatment, was initiated in 68 (54%) patients. Number of new HCC diagnoses did not differ between the two periods (n = 14 vs. 14). While personal visits were reduced, an increase in teleconsultation was observed (period 2). Number of patients with visit delays (n = 31 (30%) vs. n = 10 (10%); p = 0.001) and imaging delays (n = 25 (25%) vs. n = 7 (7%); p = 0.001) was higher in period 2. Accordingly, a reduced number of patients was discussed in interdisciplinary tumor boards (lowest number in April (n = 24), compared to a median number of 57 patients during period 1). Median number of elective/non-elective admissions was not different between the periods. One patient contracted COVID-19 with lethal outcome. CONCLUSIONS: Changes in patient care included reduced personal contacts but increased telephone visits, and delays in diagnostic procedures. The effects on long-term outcome need to be determined.


Subject(s)
COVID-19/epidemiology , Carcinoma, Hepatocellular/diagnosis , Liver Neoplasms/diagnosis , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , COVID-19/virology , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Delayed Diagnosis , Female , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Pandemics , Patients/psychology , Retrospective Studies , SARS-CoV-2/isolation & purification , Survival Rate , Telemedicine , Tertiary Care Centers
4.
Bioengineered ; 12(1): 4054-4069, 2021 12.
Article in English | MEDLINE | ID: covidwho-1348035

ABSTRACT

During the pandemic of the coronavirus disease 2019, there exist quite a few studies on angiotensin-converting enzyme 2 (ACE2) and SARS-CoV-2 infection, while little is known about ACE2 in hepatocellular carcinoma (HCC). The detailed mechanism among ACE2 and HCC still remains unclear, which needs to be further investigated. In the current study with a total of 6,926 samples, ACE2 expression was downregulated in HCC compared with non-HCC samples (standardized mean difference = -0.41). With the area under the curve of summary receiver operating characteristic = 0.82, ACE2 expression showed a better ability to differentiate HCC from non-HCC. The mRNA expression of ACE2 was related to the age, alpha-fetoprotein levels and cirrhosis of HCC patients, and it was identified as a protected factor for HCC patients via Kaplan-Meier survival, Cox regression analyses. The potential molecular mechanism of ACE2 may be relevant to catabolic and cell division. In all, decreasing ACE2 expression can be seen in HCC, and its protective role for HCC patients and underlying mechanisms were explored in the study.


Subject(s)
Angiotensin-Converting Enzyme 2/genetics , Carcinoma, Hepatocellular/genetics , Liver Cirrhosis/genetics , Liver Neoplasms/genetics , Neoplasm Proteins/genetics , Receptors, Virus/genetics , alpha-Fetoproteins/genetics , Age Factors , Aged , Angiotensin-Converting Enzyme 2/metabolism , Area Under Curve , COVID-19/virology , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Databases, Genetic , Datasets as Topic , Female , Gene Expression Regulation, Neoplastic , Humans , Liver Cirrhosis/diagnosis , Liver Cirrhosis/mortality , Liver Cirrhosis/pathology , Liver Neoplasms/diagnosis , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Middle Aged , Neoplasm Proteins/classification , Neoplasm Proteins/metabolism , Protective Factors , Protein Interaction Mapping , ROC Curve , Receptors, Virus/metabolism , SARS-CoV-2/pathogenicity , Survival Analysis , alpha-Fetoproteins/metabolism
5.
Clin Gastroenterol Hepatol ; 19(8): 1520-1530, 2021 08.
Article in English | MEDLINE | ID: covidwho-1317650

ABSTRACT

The Coronavirus disease 2019 (COVID-19) pandemic is expected to have a long-lasting impact on the approach to care for patients at risk for and with hepatocellular carcinoma (HCC) due to the risks from potential exposure and resource reallocation. The goal of this document is to provide recommendations on HCC surveillance and monitoring, including strategies to limit unnecessary exposure while continuing to provide high-quality care for patients. Publications and guidelines pertaining to the management of HCC during COVID-19 were reviewed for recommendations related to surveillance and monitoring practices, and any available guidance was referenced to support the authors' recommendations when applicable. Existing HCC risk stratification models should be utilized to prioritize imaging resources to those patients at highest risk of incident HCC and recurrence following therapy though surveillance can likely continue as before in settings where COVID-19 prevalence is low and adequate protections are in place. Waitlisted patients who will benefit from urgent LT should be prioritized for surveillance whereas it would be reasonable to extend surveillance interval by a short period in HCC patients with lower risk tumor features and those more than 2 years since their last treatment. For patients eligible for systemic therapy, the treatment regimen should be dictated by the risk of COVID-19 associated with route of administration, monitoring and treatment of adverse events, within the context of relative treatment efficacy.


Subject(s)
COVID-19 , Carcinoma, Hepatocellular , Liver Neoplasms , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/therapy , Humans , Liver Neoplasms/diagnosis , Liver Neoplasms/epidemiology , Liver Neoplasms/therapy , Neoplasm Recurrence, Local/epidemiology , Pandemics , SARS-CoV-2 , alpha-Fetoproteins
6.
J Natl Compr Canc Netw ; 19(9): 1063-1071, 2021 05 28.
Article in English | MEDLINE | ID: covidwho-1256975

ABSTRACT

BACKGROUND: Delays in diagnosis and treatment have been reported for many cancers, with resultant stage migration and worse survival; however, few data exist in patients with hepatocellular carcinoma (HCC). These data are of particular importance in light of the COVID-19 pandemic, which has caused disruptions in healthcare processes and may continue to impact cancer care for the foreseeable future. The aim of our study was to characterize the prevalence and clinical significance of diagnostic and treatment delays in patients with HCC. METHODS: We performed a retrospective cohort study of consecutive patients diagnosed with HCC between January 2008 and July 2017 at 2 US health systems. Diagnostic and treatment delays were defined as >90 days between presentation and HCC diagnosis and between diagnosis and treatment, respectively. We used multivariable logistic regression to identify factors associated with diagnostic and treatment delays and Cox proportional hazard models to identify correlates of overall survival. RESULTS: Of 925 patients with HCC, 39.0% were diagnosed via screening, 33.1% incidentally, and 27.9% symptomatically. Median time from presentation to diagnosis was 37 days (interquartile range, 18-94 days), with 120 patients (13.0%) experiencing diagnostic delays. Median time from HCC diagnosis to treatment was 46 days (interquartile range, 29-74 days), with 17.2% of patients experiencing treatment delays. Most (72.5%) diagnostic delays were related to provider-level factors (eg, monitoring indeterminate nodules), whereas nearly half (46.2%) of treatment delays were related to patient-related factors (eg, missed appointments). In multivariable analyses, treatment delays were not associated with increased mortality (hazard ratio, 0.90; 95% CI, 0.60-1.35); these results were consistent across subgroup analyses by Barcelona Clinic Liver Cancer stage and treatment modality. CONCLUSIONS: Diagnostic and therapeutic delays exceeding 3 months are common in patients with HCC; however, observed treatment delays do not seem to significantly impact overall survival.


Subject(s)
COVID-19 , Carcinoma, Hepatocellular , Liver Neoplasms , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/therapy , Humans , Liver Neoplasms/diagnosis , Liver Neoplasms/epidemiology , Liver Neoplasms/therapy , Pandemics , Retrospective Studies , SARS-CoV-2
9.
Nat Rev Dis Primers ; 7(1): 6, 2021 01 21.
Article in English | MEDLINE | ID: covidwho-1075224

ABSTRACT

Liver cancer remains a global health challenge, with an estimated incidence of >1 million cases by 2025. Hepatocellular carcinoma (HCC) is the most common form of liver cancer and accounts for ~90% of cases. Infection by hepatitis B virus and hepatitis C virus are the main risk factors for HCC development, although non-alcoholic steatohepatitis associated with metabolic syndrome or diabetes mellitus is becoming a more frequent risk factor in the West. Moreover, non-alcoholic steatohepatitis-associated HCC has a unique molecular pathogenesis. Approximately 25% of all HCCs present with potentially actionable mutations, which are yet to be translated into the clinical practice. Diagnosis based upon non-invasive criteria is currently challenged by the need for molecular information that requires tissue or liquid biopsies. The current major advancements have impacted the management of patients with advanced HCC. Six systemic therapies have been approved based on phase III trials (atezolizumab plus bevacizumab, sorafenib, lenvatinib, regorafenib, cabozantinib and ramucirumab) and three additional therapies have obtained accelerated FDA approval owing to evidence of efficacy. New trials are exploring combination therapies, including checkpoint inhibitors and tyrosine kinase inhibitors or anti-VEGF therapies, or even combinations of two immunotherapy regimens. The outcomes of these trials are expected to change the landscape of HCC management at all evolutionary stages.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/etiology , Combined Modality Therapy , Humans , Immunotherapy , Liver Neoplasms/diagnosis , Liver Neoplasms/epidemiology , Liver Neoplasms/therapy , Sorafenib
11.
DNA Cell Biol ; 40(2): 359-372, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-963006

ABSTRACT

The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the virus causing coronavirus disease 2019 (COVID-19), has been confirmed in cancers through binding specific mRNAs to invade human cells. Therefore, the aim of this study described here was to develop and validate novel SARS-CoV-2 proteins binding human mRNAs (SPBRs) signature to predict overall survival (OS) in hepatocellular carcinoma (HCC). Using multivariate Cox regression analysis, a set of SPBRs was identified to establish a multigene signature in the Cancer Genome Atlas repositories cohort. Furthermore, a nomogram was established based on the signature and clinical risk factors to improve risk stratification for individual patients. External validation was performed in the International Cancer Genome Consortium (ICGC) cohort. A six-SPBR signature was built to classify patients into two risk groups using a risk score with different OS in two cohorts (all p < 0.0001). Multivariate regression analysis demonstrated the signature was an independent predictor of HCC. Moreover, the signature presented an excellent diagnostic power in differentiating HCC and normal tissues. Gene set enrichment analysis demonstrated that high-risk group was closely enriched in cell cycle, DNA replication, microRNAs in cancer, and cytokine-cytokine receptor interaction. The novel signature demonstrated great clinical value in predicting the OS for patients with HCC, and will provide a good reference between cancer research and SARS-CoV-2 and help individualized treatment in HCC.


Subject(s)
Biomarkers, Tumor/genetics , COVID-19/complications , Carcinoma, Hepatocellular/mortality , Liver Neoplasms/mortality , Nomograms , RNA, Messenger/genetics , SARS-CoV-2/isolation & purification , Biomarkers, Tumor/metabolism , COVID-19/transmission , COVID-19/virology , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/virology , Cohort Studies , Female , Follow-Up Studies , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/diagnosis , Liver Neoplasms/genetics , Liver Neoplasms/virology , Male , Middle Aged , Prognosis , RNA, Messenger/metabolism , Survival Rate
12.
Hepatol Int ; 14(6): 920-929, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-919762

ABSTRACT

BACKGROUND: COVID-19 has been giving the devastating impact on the current medical care system. There are quite many guidelines on COVID-19, but only a few on the management of hepatocellular carcinoma (HCC) during COVID-19 pandemic. AIMS: We develop these recommendations to preserve adequate clinical practice for the management of HCC. METHODS: Experts of HCC in the Asia-Pacific region exchanged opinions via webinar, and these recommendations were formed. RESULTS: Close contact should be minimized to reduce possible exposure of both medical staff and patients to the novel coronavirus. To prevent transmission of the virus, meticulous hygiene measures are important. With the decrease in regular medical service, the medical staff may be mobilized to provide COVID-19-related patient care. However, diagnosis and treatment of HCC should not be delayed because of COVID-19 pandemic. The management of HCC should be the same as in non-pandemic circumstances. HCC is highly malignant, thus it is recommended not to delay curative treatment such as surgery and ablation. However, a kind of triage is necessary even among patients with HCC when resources are insufficient for all to be treated. Curative treatments should be periodized and cytoreductive or non-curative treatment such as vascular interventions and systemic therapy may be postponed until it can be performed safely with sufficient resources. For patients with confirmed or suspected to be infected with the novel coronavirus, diagnosis and treatment should be postponed until the virus is eliminated or they are confirmed as not being infected with it. CONCLUSIONS: These are collection of measures implemented by front-line medical professionals. We would evolve these recommendations over time as more real-world data becomes available.


Subject(s)
COVID-19 , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/therapy , Liver Neoplasms/diagnosis , Liver Neoplasms/therapy , COVID-19/complications , Carcinoma, Hepatocellular/complications , Humans , Liver Neoplasms/complications
15.
J Hepatol ; 73(2): 441-445, 2020 08.
Article in English | MEDLINE | ID: covidwho-164705

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has shattered the meticulously developed processes by which we delivered quality care for patients with cirrhosis. Care has been transformed by the crisis, but enduring lessons have been learned. In this article, we review how COVID-19 will impact cirrhosis care. We describe how this impact unfolds over 3 waves; i) an intense period with prioritized high-acuity care with delayed elective procedures and routine care during physical distancing, ii) a challenging 'return to normal' following the end of physical distancing, with increased emergent decompensations, morbidity, and systems of care overwhelmed by the backlog of deferred care, and iii) a protracted period of suboptimal outcomes characterized by missed diagnoses, progressive disease and loss to follow-up. We outline the concrete steps required to preserve the quality of care provided to patients with cirrhosis. This includes an intensification of the preventative care provided to patients with compensated cirrhosis, proactive chronic disease management, robust telehealth programs, and a reorganization of care delivery to provide a full service of care with flexible clinical staffing. Managing the pandemic of a serious chronic disease in the midst of a global infectious pandemic is challenging. It is incumbent upon the entire healthcare establishment to be strong enough to weather the storm. Change is needed.


Subject(s)
Betacoronavirus , Coronavirus Infections/prevention & control , Delivery of Health Care/trends , Liver Cirrhosis/therapy , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Quality of Health Care/trends , COVID-19 , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/etiology , Clinical Decision-Making/methods , Coronavirus Infections/virology , Humans , Liver Cirrhosis/complications , Liver Cirrhosis/mortality , Liver Neoplasms/diagnosis , Liver Neoplasms/etiology , Patient Care Team , Pneumonia, Viral/virology , SARS-CoV-2 , Telemedicine/methods
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