The use of alternative therapeutic approaches in advanced carcinogenesis is a growing investigative base. One such cancer, primary liver cancer, is one of the most commonly occurring cancers worldwide and often presents in late stage disease consequently preventing traditional curative modalities. As a result, hepatocellular carcinoma (HCC), representing the majority of primary liver cancer, is the third most common cause of cancer-related deaths globally. Survival rates are linked to stage of presentation as well as concomitant cirrhosis limiting the 5-year survival in these patients to < 20%. Alternative strategies are in dire need as patients in this cohort have limited palliative options. Currently, sorafenib is the only approved systemic therapy; however, it has a limited survival advantage and low efficacy prompting the empirical need for further evaluation. Understanding of cancer therapy has led to an enhanced focus on the Notch pathway as a potential target for advanced HCC. Notch signaling is a critical component of development and cell fate and has been linked to various modalities including liver regeneration and as a key driver in carcinogenesis. In this review, we will provide a review of the current status of the Notch signaling in liver cancer and of Notch as an alternative potential strategy for advanced HCC.
Aim: Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. If left untreated, liver cancer has a poor prognosis with more than 90% of patients dying of the disease within 5 years of diagnosis. The aim of this study is to assess the value of combined radiofrequency ablation (RFA), followed by trans-arterial chemoembolization (TACE) in the management of HCC.
Methods: Fifty HCC patients with chronic liver disease were categorized into two groups according to the modality of locoregional treatment: 25 HCC patients treated with RFA followed by TACE within 5 days and 25 HCC patients treated with TACE only.
Results: Complete response was achieved in 100% and 84% of the HCC patients after 1 month from combined RFA-TACE therapy and TACE only respectively. The rate of objective response after 7 months was 84% and 44% in the RFA-TACE and TACE groups respectively. One year disease free survival rate was 56% and 24% in RFA-TACE and TACE groups respectively, and overall survival rate was 88% in the RFA-TACE group and 80% in the TACE only group.
Conclusion: Combined RFA-TACE appears to be an effective modality and superior to TACE only for the treatment of HCC.
Aim: The aim was to assess the impact of hyperglycemia on the recurrence of hepatocellular carcinoma (HCC) as well as evaluate survival after curative ablation by radiofrequency.
Methods: This study, which was conducted retrospectively on 107 chronic hepatitis C (CHC) patients with 159 HCCs, was presented to the Hepatology Unit of Internal Medicine Department at Tanta University Hospitals. All lesions were curatively treated by radiofrequency ablation (RFA) and the surveillance of HCC recurrence was evaluated radiologically every 3 months for periods between 6 and 36 months. Of 107 subjects, 70 were males and 37 were females, with mean age 50.4 ± 9.4 years. All patients were divided according to their glycemic state into the following three groups: Group I, which included 37 type 2 diabetic patients, with adequate maintenance of blood glucose, has 52 HCCs; Group II, which included 25 type 2 diabetic patients with inadequate maintenance of blood glucose, has 43 HCCs; and Group III, which included 45 euglycemic non-diabetic patients, has 64 HCCs.
Results: Our results showed that, there was significant increase in recurrence rate in diabetic patients with inadequate maintenance of blood glucose (Group II) compared to those in Group I and Group III (P < 0.0001). Interestingly, there was no significant difference concerning HCC recurrence between diabetic patients with adequate maintenance of blood glucose (Group I) and non-diabetic euglycemic patients (Group III). Our results also identified that, inadequate maintenance of blood glucose in diabetic patients was also a significant predictor of poor survival.
Conclusion: Inadequate maintenance of blood glucose in diabetic patients is a significant risk factor for recurrence of HCC and for poor survival after curative RFA therapy in CHC patients.
Aim: This paper reported the experience of one center on repeat laparoscopic liver surgery for metastasis and hepatocellular carcinoma (HCC) with a review of the literature.
Methods: This retrospective study included 24 patients who underwent laparoscopic re-intervention (hepatic resection and radiofrequency ablation) for recurrent HCC in cirrhosis (n = 17) and for recurrent malignant metastases (n = 7) after a previous open or laparoscopic procedure. Patients were divided into two groups according to the first surgical approach. Group 1 underwent open resection and laparoscopic procedure (7 patients), and Group 2 underwent laparoscopic resection and laparoscopic procedure (17 patients).
Results: Mean operative time for re-intervention was significantly longer for Group 1 (220.14 ± 80.06 min) than for Group 2 (150 ± 56.18 min; P = 0.001), whereas the mean blood loss and mean hospital stay were comparable in both groups. According to Dindo-Clavien classification, overall morbidity ranged between Grade I and IIIa and was similar in both groups.
Conclusion: This study suggests that repeat laparoscopic surgery for recurrent hepatic malignant diseases in selected patients is a feasible and safe procedure with good short-term outcomes, but further prospective studies are needed to support these results.
Aim: The aim was to analyze the feasibility of salvage liver transplant after liver resection in hepatocellular carcinoma (HCC) with hepatitis C virus (HCV) etiology.
Methods: All the patients diagnosed with HCC with HCV etiology who underwent living donor liver transplant from July 2002 to November 2012 were studied. Their recurrence rate, mortality, and prognostic factors were analyzed and compared between primary transplant and salvage transplant for up to 5 years post-transplant.
Results: One hundred and nine patients underwent a liver transplant for HCC associated with HCV etiology within the University of California, San Francisco criteria. Eighteen were post-hepatectomy salvage transplants and 91 were primary transplants. Median follow-up time was 31 months. One, 3 and 5 years overall survival rates were 76%, 76% and 65% in the salvage group, and 92%, 85% and 85% in primary transplant group respectively. The difference in overall survival rates was statistically significant (P = 0.031). However, recurrence-free survivals for 1, 3 and 5 years were 72%, 72% and 46% for salvage group, and 91%, 73% and 46% for primary transplant group; which were not statistically significant (P = 0.328).
Conclusion: Salvage transplantation for post-hepatectomy recurrence for patients with HCC associated with HCV-related chronic liver disease seems to offer inferior overall survival rates than primary transplantation.
Hepatic sarcomatoid carcinomas are very rare. The majority of cases contain sarcomatoid features with either hepatocellular carcinoma (HCC) or cholangiocarcinoma (CC) elements alone. These are aggressive tumors and carry an unfavorable prognosis. We describe an extremely rare tumor sub-type of combined sarcomatoid HCC and CC in a hepatitis B virus carrier presenting with abdominal pain. Pre-operative imaging suggested a segment VI hepatocellular cancer with no metastatic spread. En bloc surgical resection with the right adrenal gland, Gerota’s fascia and right hemidiaphragm was performed. The patient suffered early peritoneal tumor recurrence and lymph node metastasis. Pre-operative diagnosis of such sarcomatoid tumors is difficult. Current evidence for adjuvant treatment is also limited. Prognosis of these patients remains extremely poor, and surgery appears to be the only curative option in cases of early disease. It is essential that clinicians carry a high index of suspicion and awareness of this rare pathological entity to improve patient outcome.
Combined hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) is a rare tumor entity. In this report, we describe a case of a young patient who developed a liver tumor in a cirrhotic liver caused by cystic fibrosis. All diagnostic findings suggested that this tumor was an HCC. We performed living donor liver transplantation. Histological examination of the tumor revealed combined HCC and CC as an incidental finding. Two years after the transplantation, the patient is in good clinical condition and is disease-free.
The treatment of hepatocellular carcinoma (HCC) in elderly patients is unclear. In particular, the efficacy and safety of sorafenib as a systemic treatment in these patients is still under debate. We performed a concise review of sorafenib therapy in this population. However, it is important to make any decisions on treatment for elderly patients with HCC through a multidisciplinary team that includes experts in the liver disease. Patients with good clinical conditions should be treated with sorafenib.
Hepatoma is a common cancer that can be seen around the world and clinical correlation between infection and hepatoma is evident. Hepatitis virus infection is proved for its relationship with hepatoma. However, the knowledge of other infections is still limited. In this short review, the relationship between hepatoma and some trematode infestation including echinococcosis fascioliasis, opisthorchiasis, clonorchiasis and schistosomiasis are described and discussed. Opisthorchiasis and clonorchiasis are confirmed for cholangiocarcinoma carcinogenesis but still lack evidence for hepatoma carcinogenesis. Schistosomiasis can increase the severity of hepatoma.
Aim: This study was conducted to assess the in vivo and in vitro anti-tumor effects of diallyl disulfide (DADS) against Ehrlich ascites carcinoma (EAC) and to suggest its probable mechanism of action.
Methods: EAC was induced in female mice by intraperitoneal injection of EAC-cells from stock mice. EAC-bearing mice were orally treated with 100 mg/kg body weight for 2 weeks beginning from the 1st day of EAC intraperitoneal transplantation. Cytotoxicity effects of DADS against EAC-cells in vitro were investigated at different concentrations (0, 6.25, 12.5, 25, 50, and 100 μg/mL) of DADS using trypan blue exclusion assay.
Results: Data from this study exhibited a significant decrease in EAC-aliquot volume as well as total and alive EAC-cell number and a marked increase in dead EAC-cell number and percent in EAC-bearing mice treated with DADS as compared with EAC-bearing control. These changes were consistent with increased number of cells which exhibited phenotypic apoptotic signs marked by a decrease in the expression of anti-apoptotic protein Bcl-2, an increase of pro-apoptotic and cell cycle arrest mediator p53 and an elevation of DNA fragmenting indicator terminal deoxynucleotidyl transferase in EAC-bearing mice treated with DADS. In addition, the tumor marker sialic acid level was markedly decreased in plasma and Ehrlich ascites in EAC-bearing mice treated with DADS. In vitro, DADS also produced anti-proliferative and anti-tumor cytotoxic potentials against EAC.
Conclusion: DADS may have anti-cancer effects which may be mediated via modulation of apoptosis and cell cycle arrest.
Aim: Aflatoxin B1 (AFB1) and fumonisin B1 (FB1) are important food-borne mycotoxins. Co-contamination of foodstuffs with these two mycotoxins is well-known and has been implicated in a possible development of hepatocellular carcinoma in humans living in regions of the world where exposures to these mycotoxins in grain are greatest. The aim of the current study was to evaluate the potential protective effects of an aqueous extract of Cochorus olitorius (C. olitorius, moroheiya) against cytotoxicity of AFB1 and/or FB1 in H4IIE-luc rat hepatoma cells, using assays to measure cell viability and disruption of DNA integrity. Although this transactivation assay was originally developed to specifically respond to aryl hydrocarbon agonists, this cell line was used because of its hepatic origin.
Methods: H4IIE-luc cells were incubated with different concentrations of AFB1 and/or FB1 for 24 and 48 h with or without aqueous extract of C. olitorius.
Results: Both mycotoxins decreased cell viability and increased DNA damage. Cytotoxicity was more pronounced when cells were exposed simultaneously to AFB1 and FB1.
Conclusion: Aqueous extract of C. olitorius protected cells against cytotoxicity of mycotoxins. C. olitorius contains a water-soluble, natural chemo-preventative agent for cancer that should be isolated and identified.
Aim: The optimal treatment for hepatocellular carcinoma (HCC) is either surgical resection or liver transplantation, but only one-third of the patients are suitable candidates for surgery. Laparoscopic radiofrequency ablation (RFA) in selected patients is a safe, feasible technique, which has proved to be superior to the percutaneous approach in patients with severe liver disease or in lesions in which the percutaneous approach is impossible. The aim of this study is to present our experience with laparoscopic RFA and demonstrate its safety as an alternative therapeutic procedure in selected patients with HCC.
Methods: This is a retrospective study of patients with HCC who underwent laparoscopic RFA between March 2009 and December 2014.
Results: Thirty-two patients with 37 tumors underwent laparoscopic RFA. Median tumor size was 2.24 cm (0.7-4.45 cm). Major complications occurred in 8 patients. Initial complete ablation was achieved in 94.6% (35/37) lesions and sustained complete ablation rate was 62.85% (22/35). Overall survival rates at 1-, 2-, and 3-year were 89%, 67.5%, and 40%, respectively.
Conclusion: Laparoscopic RFA of HCC is safe and the long-term outcomes are similar to those achieved with liver resection. Further trials combining chemoembolization and RFA are needed to improve long-term outcomes and to limit local tumor progression.
Aim: Used as a palliative therapy for unresectable liver cancer, radiofrequency ablation (RFA) is associated with the induction of immunological responses. Here, we show strong evidence of tumor-specific peripheral blood mononuclear cells (PBMCs) 12 months after RFA.
Methods: Three patients with colorectal cancer (CRC) metastases to the liver and two patients with primary hepatocellular carcinoma (HCC) were enrolled in this study. PBMC, isolated 12 months after RFA, were stimulated with normal and tumor tissue lysate. Interferon gamma secretion was evaluated by flow cytometry and indirectly, by luciferase assay for adenylate kinase activity in PBMC-stimulated lysates of target cells. Baseline data were detected before RFA and 4 weeks after treatment.
Results: Two CRC patients and one HCC patient had recurrence-free survival. One patient with CRC developed secondary metastases; one patient with HCC developed a local recurrence. Recurrence-free patients showed a significantly higher cytolytic activity of PBMC against matched tumor cells 12 months after RFA treatment. Interestingly, patients with malignant recurrence showed a decreased cytolytic activity.
Conclusion: RFA seems to overcome immune-tolerance toward tumor antigens and/or presents new tumor antigens. Patients seem to benefit from a prolonged increase in cytolytic activity. The immune-modulatory effects of RFA need further investigations in multimodality anticancer therapies.
Aim: Hepatitis B virus (HBV) infection is a major cause of chronic liver diseases. Sorafenib is a multikinase inhibitor and an approved anti-liver cancer drug. Here we demonstrated the antiviral effect of sorafenib on HBV gene expression.
Methods: To investigate the effect of sorafenib on HBV gene expression, a luciferase assay was performed with × 1.3 Cp-luciferase HBV construct and reverse transcriptase polymerase chain reaction (PCR), real-time PCR, and Western blotting analyses were performed using HepG2 cells derived from hepatocellular carcinoma and Chang liver cells derived from a normal liver tissue.
Results: Sorafenib suppressed HBV gene expression via inhibiting the JNK pathway. In this process, the farnesoid X receptor (FXR), a transcription factor that has been reported to increase HBV replication and gene expression, was under control of the JNK pathway. Notably, JNK activation increased FXR protein levels, not mRNA levels.
Conclusion: Sorafenib suppressed HBV gene expression via inhibiting the JNK pathway, which regulates FXR activity.
Hepatocellular carcinoma (HCC) with inferior vena cava (IVC) invasion and metastatic lymph node metastases has a poor prognosis, and surgical resection is seldom indicated. We report how an initially unresectable HCC in a 36-year-old Chinese male with distant lymph node metastases and tumor thrombosis in the IVC was successfully downstaged and ultimately resected together with the IVC. After the disease had been downstaged, curative resection of the tumor and IVC was conducted with immediate reconstruction of the IVC. The patient has survived for more than 2 years after the surgery. In conclusion, tumor and IVC resection can cure metastatic HCC after downstaging treatment combining sorafenib and transarterial chemoembolization.
Liver diseases are most common disorders in the world and characterized by rapid changes from steatosis to chronic hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Natural products that attained great attention is to be used in the prevention and treatment of multiple diseases in humans. Several researches have been reported numerous natural and phytochemical compounds that may counteract or prevent the hepatic injury and primary liver cancer. The conservative treatment of liver toxicity and HCC may face awkward challenges in chemotherapy such as therapeutic failure or drug resistance. Accordingly, there is an actual need for safe and effective therapeutic and preventive modalities for liver disorders. The present review aims to focus on the potential protective and therapeutic effects of natural compounds in prevention and treatment of hepatotoxicity and HCC. It also demonstrates the mechanism of the natural products in enzymatic regulation of antioxidants and its role in apoptosis and proliferation of cancerous lesions of hepatocytes. Accordingly, it highlights the promising role of natural bioactive compounds and provides the rational for further transitional researches, and emphasize on the scientific validation of natural compounds for therapeutic portfolio for clinical use in liver diseases.
Hepatocellular carcinoma (HCC) is the fifth commonest cause of malignancy and the third cause of cancer mortality. There are different treatment options for HCC ranging from loco-regional therapy to surgical treatment. Different regimen of systemic chemotherapy has been tried with a poor response. Several studies aimed at discovering more molecules for the management of HCC. Those studies aimed at recognizing and targeting several signalling and molecular pathways that lead to cellular proliferation and tumour formation. In this review, we discussed the role of several agents found in natural and dietary products such as curcumin, resveratrol, flavonoids, Rubus aleaefolious Poir total alkaloids, Livistona chinesis seed, and crocetin. We had used the names of the above-mentioned products as key words in addition to “Hepatocellular Carcinoma” on PubMed to find studies that discussed their roles in HCC. Articles were downloaded for reviewing and discussing natural products that had adequate studies in treating HCC.
Aim: The present study was conducted to investigate the protective effect of chamomile flowers (CFME) and fennel seeds methanolic (FSME) extracts on azathioprine (AZA), an immunosuppressant drug, which induced liver injury and oxidative stress in rats.
Methods: Rats were divided into 6 groups (8 rats each) and treated orally for 28 consecutive days as follows. Group 1: rats were given normal saline and used as controls; group 2: rats treated with CFME (200 mg/kg); group 3: rats treated with FSME (200 mg/kg); group 4: rats treated with AZA (25 mg/kg); groups 5 and 6: rats treated with CFME (200 mg/kg) or FSME (200 mg/kg) 15 min prior to AZA (25 mg/kg) treatment. At the end of experimental period, blood and liver samples were collected from all groups for the biochemical analysis and histological examination.
Results: The obtained data revealed that AZA induced hepatic injury in the rats as evidenced by the significant increase in serum aspartate aminotransferase, alanine aminotransferase, alkaline phospatase, cholesterol, and direct bilirubin as well as hepatic malondialdehyde level accompanied with significant decrease in reduced glutathione content and total antioxidant capacity in the liver. Moreover, body weight gain showed significant decrease and relative liver weight showed significant increase on AZA treatment. The sequential significant changes in biochemical parameters were accompanied by severe histological changes in the liver tissue, including hepatocytes disorganization with pyknotic nuclei, fatty degeneration, congestion, fibrosis and bile duct necrosis around the portal tract. Areas of hemorrhages in blood vessels and in between hepatocytes were also seen. However, the results showed potential hepatoprotective effects of CFME and FSME against AZA-induced liver injury and oxidative stress. They succeeded to restore the biochemical parameters and improve the histological picture of the liver. This improvement was more pronounced in the rats pretreated with FSME.
Conclusion: It could be concluded that CFME and FSME have hepatoprotective potentials against AZA probably due to their antioxidant properties and radical scavenging activity.
Aim: Protective effects of aqueous extract of Amaranthus hybridus against aflatoxin B1 (AFB1) and/or fumonisin B1 (FB1) on the H4IIE-luc cell line were determined by use of the methyl thiazol tetrazolium viability assay and disruption of DNA integrity.
Methods: H4IIE-luc cells were incubated with different concentrations of AFB1 and/or FB1 for 24 and 48 h with or without aqueous extract of A. hybridus.
Results: AFB1 decreased viability of cells after 24 and 48 h of exposure. EC50 values for AFB1 were 10.5 and 1.8 µmol/L for the two periods respectively. When the 48 h exposure to mycotoxin repeated with a pre-treatment of 20 and 40 µg/mL extract of A. hybridus, the EC50 changed to 3.88 and 7.67 µmol/L, respectively. H4IIE-luc cells exposed to FB1 for 24 h responded more than those incubated for 48 h. Cells treated with a combination of AFB1 and FB1 were less viable with a significant decrease at the greater concentration. The mixture of AFB1 and FB1 resulted in a significant threat to H4IIE-luc as indicated by the absence or appearance of new bands in random amplified polymorphic DNA analysis, which demonstrated damage to DNA. The protective effects were probably due to greater content of total phenolics, carotenoids, β-carotene, folic-, linolenic-, linoleic and palmitic acids, as well as calcium, magnesium, iron, zinc, and selenium observed in the extract.
Conclusion: Exposure to 40 μg/ml of extract of A. hybridus protected cells from damage to DNA by stabilizing DNA.
Aim: Hepatocellular carcinoma (HCC) is the dominant form of primary liver cancer and is histologically and etiologically distinct from other forms of primary liver cancer. The objective of this study was to elucidate the synergistic effect and the role of chicory extract [inulin (IN)] as a chemo-sensitizer for cisplatin (CIS) treatment of HCC.
Methods: Five groups of rats were treated for 4 months. These groups consisted of the control group, a group receiving thioacetamide (TAA) (200 mg/kg b.w) in drinking water, a group injected intraperitoneally with a single dose of CIS (7.5 mg/kg b.w) in addition to TAA for 4 months, a group receiving oral doses of IN (10 mg/kg b.w) in addition to TAA for 4 months, a group injected intraperitoneally with a single dose of CIS (7.5 mg/kg b.w) and IN (10 mg/kg b.w) plus TAA for 4 months.
Results: The current data exhibited increment of serum and liver enzyme (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatine kinase, and lactate dehydrogenase) activity, serum lipid profile levels (total lipids, total cholesterol, triglycerides, low density lipoprotein and very low density lipoprotein), and a significant increase in α-fetoprotein and bilirubin, accompanied with reduced total serum protein and albumin levels in a HCC rat model. Histopathologically, numerous alterations were detected in hepatic tissues of HCC rats, such as lymphocytic cell infiltration, damage of hepatocytes, dilated congested central vein with degenerated endothelial cells, and congested blood sinusoids in addition to Masson’s trichrome staining blue collagen fibers in hepatocytes and central vein indicating hepatic fibrosis. Treatment of HCC rats with CIS or IN improved such deleterious effects, where IN is more effective than cisplatin and the best effect can be observed in rats that received both cisplatin and IN.
Conclusion: It could be concluded that IN in chicory extract acts as a chemo-sensitizer to CIS for treatment in a HCC rat model.
Hepatocellular carcinoma (HCC) is frequently complicated by cirrhosis, and it is not unusual for treatment options to be limited as a result of pancytopenia due to hypersplenism. Partial splenic embolization (PSE) has been performed for thrombocytopenia resulting from hypersplenism. However, the safety and efficacy of concurrent transcatheter arterial chemoembolization (TACE) with PSE for HCC remain unclear. Thrombocytopenia has been improved and treatment continued using concurrent PSE. In addition, hepatic functional reserve could be maintained even after treatment for HCC. Concurrent TACE and PSE for HCC with thrombocytopenia can be expected to help maintain hepatic reserve, and it may contribute to improving the prognosis of HCC. Hence, PSE could lead to an asplenic state. The appearance of Howell-Jolly bodies on a peripheral blood smear is reported useful for assessing splenic function. The appearance of Howell-Jolly bodies is associated with an increased risk for post splenectomy sepsis/overwhelming postsplenectomy infection in patients with reduced splenic function. These bodies are frequently observed in peripheral erythrocytes after PSE, and when they are present, it is appropriate to administer pneumococcal vaccine to prevent severe infection. The expectations for PSE combined with TACE for the treatment of HCC associated with cirrhosis are reviewed.
Microwave coagulation therapy (MCT) is a relatively new method of tumor ablation compared to other minimally invasive local therapies for hepatocellular carcinoma (HCC). It is a thermal ablation modality based on the application of heat, potentially leading to larger ablation zones. In recent years, there is a steady increase in the application of this modality to the treatment of HCC because it offers several advantages in the management of tumors larger than 3 cm in diameter. This article reviews the advances in MCT for the treatment of HCC in recent years including its brief history, basic principles, main technical parameters, safety issues, current status in clinical application, limitations, and future perspectives.
A selection of patients with hepatocellular carcinoma (HCC) for surgical resection is crucial and algorithms/staging systems help surgeons to decide on a standard treatment for each patient and each HCC stage. However, there are always difficulties in remembering and/or recalling the contents of the algorithms/staging systems. Moreover, most algorithms/staging systems don’t include data about the extent of hepatectomy, intra-hepatic distribution of tumor(s), and technical feasibility of resection, all of which are vital in the surgeons’ decision-making process. Here, we aimed to present a simple and handy mnemonic acronym for selecting resectable HCCs in surgical practice. This was reproduced from the existing well-known staging systems. The designed mnemonic acronym is a phrase “PERISH” and it includes asking for Performance of patient, Extra-hepatic disease, Reserve of liver, Intra-hepatic distribution, Stratifying risk factors, and Hepatectomy size in order. Performance based on whether the patient is mostly bedridden or not, should be the first step of evaluation. Next, asking for suspicious metastasis as bone pain and radiological evaluation of abdomen/thorax is mandatory. The calculation of Child-Pugh score is only the third step. Good candidates for surgical resection should be Child-Pugh “A” with normal bilirubin levels. Technical feasibility of resection according to the intra-hepatic distribution of tumor(s) should be done later and the candidates preferably should not have portal hypertension (no splenomegaly, no thrombocytopenia). If the patient fulfils all the previous steps, the surgeon may perform indo-cyanine green clearance test. Consequently, following the PERISH flowchart may prevent “perish” of the surgeons while selecting the appropriate resectable HCCs.