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Repeat hepatectomy (RH) and microwave ablation (MWA) are frequently used procedures for the treatment of recurrent hepatocellular carcinoma (HCC) after curative resection. This study aimed to compare the long-term outcomes of RH and MWA for solitary and small HCC with early or late recurrence.This retrospective study enrolled patients who underwent RH or MWA for solitary and small (≤3 cm) recurrent HCC at Tongji hospital between April 2006 and December 2020. Propensity score matching (PSM) was further employed to analyze the prognosis of different treatment methods.A total of 256 patients were analyzed, of whom 94 and 162 underwent RH and MWA, respectively. The overall treatment-related complication rate was higher in the RH group. Both recurrence-free survival (RFS) and overall survival (OS) rates of RH were significantly better than those of MWA. Multivariate analysis showed that MWA, early recurrence (within 24 months after initial resection), cirrhosis, and AFP400 ng/ml were independent risk factors for poor prognoses of recurrent HCC. The stratified analysis demonstrated that MWA and RH had similar long-term outcomes in patients with early recurrence. Nevertheless, MWA had worse RFS and OS than RH in patients with late recurrence. The same results were obtained in the PSM analysis.The long-term outcomes of HCC patients with late recurrence were significantly better than those with early recurrence. RH should be the first choice for solitary small recurrent HCC patients with late recurrence, while MWA should be selected for those with early recurrence.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer with a high mortality rate worldwide. The percentage of HCC patients with vascular invasion is high. However, tumor thrombus in the hepatic vein (HVTT) has a lower incidence than tumor thrombus in the portal vein (PVTT). Conventionally, HCC patients with HVTT are treated the same as HCC patients with PVTT and offered sorafenib or other systemic agents. However, according to recent studies, it is evident that HCC with HVTT shows different outcomes when classified into different subgroups. In this review, we discuss the recent progress and changes in treatment of HCC with HVTT.

Background The purpose of the study was to evaluate the diagnostic value of gamma‐glutamyl transpeptidase to alkaline phosphatase ratio (GAPR) combined with gamma‐glutamyl transpeptidase to aspartate aminotransferase ratio (GAR) and alanine aminotransferase to aspartate aminotransferase ratio (AAR) in alpha‐fetoprotein (AFP)‐negative hepatocellular carcinoma (HCC). Methods A total of 925 AFP‐negative patients, including 235 HCC patients, 213 chronic hepatitis (CH) patients, and 218 liver cirrhosis (LC) patients, as well as 259 healthy controls were enrolled in this study. The differences of laboratory parameters and clinical characteristics were analyzed by Mann–Whitney U or Kruskal–Wallis H‐test. Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic value of GAPR, GAR, and AAR in AFP‐negative HCC (AFP‐NHCC) patients. Results GAPR, GAR, and AAR were important parameters closely related to AFP‐NHCC. The combination of GAPR, GAR, and AAR was most effective in differentiating AFP‐NHCC group from control group (AUC = 0.875), AFP‐negative CH group (AUC = 0.733), and AFP‐negative LC group (AUC = 0.713). GAPR combined with GAR and AAR exhibited a larger AUC than single ratio or pairwise combination for distinguishing AFP‐NHCC group with TNMⅠstage, BCLC stage A, and tumor size less than 3 cm. The diagnostic value of GAPR combined with GAR and AAR was higher in AFP‐NHCC and was also reflected in the TNM stage, Barcelona Clinic Liver Cancer (BCLC) stage and tumor size. Conclusions GAPR combined with GAR and AAR were effective diagnostic markers of AFP‐NHCC, especially in patients with good liver function, early stage or small size., Gamma‐glutamyl transpeptidase to alkaline phosphatase ratio combined with gamma‐glutamyl transpeptidase to aspartate aminotransferase ratio and alanine aminotransferase to aspartate aminotransferase ratio were effective diagnostic markers of alpha‐fetoprotein‐negative hepatocellular carcinoma, especially in patients with good liver function, early stage or small size.

Background: Understanding risk factors for vascular invasion (VI) is crucial for assessing the risk of recurrence and overall prognosis of hepatocellular carcinoma (HCC). This study aimed to construct a prognostic long non-coding RNA (lncRNA) signature and a ceRNA Network associated with vascular invasion in HCC. Methods: Differentially expressed genes (DEGs) of HCC patients associated with VI were identified by analyzing data from TCGA. Weighted gene co-expression network analysis (WGCNA) was used to identify associations between gene expression modules and clinical features. A VI-related prognostic lncRNA signature was then established using univariate, LASSO and multivariate Cox proportional hazards regression analyses. Based on the hub modules identified by the WGCNA, we constructed a VI-related lncRNA-miRNA-mRNA ceRNA network and screened hub lncRNAs for further research. Finally, we conducted in vitro and in vivo experiments to determine the biological roles of the identified hub gene BBOX1-AS1. Results: The key module related to VI and OS was identified using WGCNA, after which a prognostic model consisting of eight lncRNAs was established, and verified using time-dependent receiver operating characteristic (ROC) curve analysis. BBOX1-AS1 was confirmed to be highly expressed in HCC tissues, and its expression was significantly correlated with a poor prognosis. Silencing BBOX1-AS1 in vitro significantly suppressed the proliferation, migration and invasion of HCC cells. In vivo experiments demonstrated that knocking down of BBOX1-AS1 could result in significant decrease of tumor volume and tumor weight. Conclusions: The VI-related lncRNA signature established in this study can be used to predict the clinical outcomes of HCC patients. In addition, we constructed a VI-related lncRNA-miRNA-mRNA ceRNA network and demonstrated that BBOX1-AS1 might be a novel biomarker associated with VI in HCC.

Most patients diagnosed with hepatocellular carcinoma (HCC) have advanced diseases, and many are not eligible for curative therapies. There is growing evidence suggesting that the combination treatment of PD-1/PD-L1 inhibitors and tyrosine kinase inhibitors (TKIs) is becoming a prospective trend for advanced HCC. For those HCC patients with sorafenib resistance, the efficacy of regorafenib combined with PD-1/PD-L1 inhibitors remains unclear. Herein, we represent a case of HCC with lung metastasis in the setting of Hepatitis B virus (HBV)-induced liver cirrhosis responding dramatically to the sequential treatment with regorafenib followed by PD-1 inhibitor after initial liver resection. A 51-year-old man diagnosed with alpha fetoprotein (AFP)-negative HCC underwent liver resection in September 2015 and was found to have solitary liver recurrence and multiple lung metastases in March 2017. He received microwave coagulation therapy (MCT) and trans-arterial chemoembolization (TACE) for liver tumor and treatment was started with sorafenib 400 mg twice daily for controlling lung metastases. In December 2018, an abdominal computerized tomography (CT) scan showed two new lesions in the liver. In March 2019, disease progression of lung metastases was measured and he received 160 mg regorafenib once daily. After a short period of partial response, in December 2019, due to the progression of the disease, he started treatment with regorafenib 160 mg in combination with sintilimab (PD-1 inhibitor) (200 mg, 3 weeks as a cycle). Surprisingly, after five cycles of sintilimab injection, he showed complete response in target lesions. There was no clinical evidence of disease progression, and the side-effects were mild. The current overall survival (OS) is 58 months. Data from this clinical case report suggest that sequential treatment with regorafenib followed by PD-1 inhibitor is a promising therapeutic option for sorafenib-refractory cases of HCCs., Video abstract Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/9Hw8vlnbtNA

Severity of liver cirrhosis plays an important role in determining the safe extents of hepatectomy in patients with hepatocellular carcinoma (HCC). The aim of this study was to investigate whether direct liver stiffness measurement can help surgeons to evaluate the severity of liver cirrhosis in HCC patients. Overall, 119 HCC patients who underwent open hepatectomy were retrospectively studied. The severity of liver cirrhosis was histologically staged using the Laennec staging system. Direct liver stiffness measurement was performed during operation using a sclerometer device named LX-C Shaw hardmeter, and its efficacy in assessing the severity of liver cirrhosis was compared with that of transient elastography (TE) and cirrhotic severity scoring (CSS) previously proposed by our team. Liver stiffness measured by LX-C Shaw hardmeter was significantly correlated with the severity of liver cirrhosis. Spearman correlation coefficients for the correlation between the severity of liver cirrhosis and direct liver stiffness measurement, TE, and CSS were 0.751, 0.454, and 0.705, respectively (all P

For patients with portal hypertension (PH), portal vein thrombosis (PVT) is a fatal complication after splenectomy. Postoperative platelet elevation is considered the foremost reason for PVT. However, the value of postoperative platelet elevation rate (PPER) in predicting PVT has never been studied.To investigate the predictive value of PPER for PVT and establish PPER-based prediction models to early identify individuals at high risk of PVT after splenectomy.We retrospectively reviewed 483 patients with PH related to hepatitis B virus who underwent splenectomy between July 2011 and September 2018, and they were randomized into either a training (Multivariate analysis exhibited that the first and third days for PPER (PPER1, PPER3) were strongly associated with PVT [odds ratio (OR): 1.78, 95% confidence interval (CI): 1.24-2.62,PPER1 and PPER3 are effective indicators for postoperative prediction of PVT. We have successfully developed PPER-based practical models to accurately predict PVT, which would conveniently help clinicians rapidly differentiate individuals at high risk of PVT, and thus guide the adoption of timely interventions.

Background. Cirrhotic severity scoring (CSS) is a noninvasive method that can predict histological severity of cirrhosis. This study is aimed at assessing the predictive value of CSS on long-term outcomes after curative hepatectomy for patients with hepatitis B virus- (HBV-) related hepatocellular carcinoma (HCC) and Child-Pugh grade A liver function and further developing novel nomograms to preoperatively predict posthepatectomy recurrence and survival. Methods. Consecutive patients who underwent curative hepatectomy for HCC between 2008 and 2014 were retrospectively studied. According to the CSS, patients were subclassified into 3 groups: no/mild, moderate, and severe cirrhosis. The impact of CSS on recurrence-free survival (RFS) and overall survival (OS) was assessed. Furthermore, RFS and OS nomograms were developed. Results. The 5-year RFS and OS rates were 36.1% and 62.8% in the no/mild cirrhosis group, compared with 28.4% and 56.2% in the moderate cirrhosis group, and 16.2% and 33.0% in the severe cirrhosis group. Long-term survival outcomes were significantly worse with the increment of cirrhotic severity. CSS, alpha-fetoprotein level, tumor size, tumor number, and macrovascular invasion were identified as independent predictors of both RFS and OS. Besides, albumin-bilirubin grade was an independent risk factor of OS not RFS. RFS- and OS-predictive nomograms based on these preoperative variables were built. For these 2 nomograms, the C-indexes were 0.696 and 0.732, respectively. Calibration curves exhibited good agreement between actual observation and nomogram prediction. Conclusions. CSS was a predictor for long-term outcomes in HCC patients after curative hepatectomy. The novel nomograms exhibited accurate preoperative prediction of posthepatectomy recurrence and OS.

Hepatocellular carcinoma (HCC) is usually associated with varying degrees of cirrhosis. Among cirrhotic patients with solitary HCC in the absence of macro-vascular invasion, whether tumor size drives prognosis or not after hepatectomy remains unknown. This study aimed to investigate the prognostic impact of tumor size on long-term outcomes after hepatectomy for solitary HCC patients with cirrhosis and without macrovascular invasion. A total of 813 cirrhotic patients who underwent curative hepatectomy for solitary HCC and without macrovascular invasion between 2001 and 2014 were retrospectively studied. We set 5 cm as the tumor cut-off value. Propensity score matching (PSM) was performed to minimize the influence of potential confounders including cirrhotic severity that was histologically assessed according to the Laennec staging system. Recurrence-free survival (RFS) and overall survival (OS) were compared between the two groups before and after PSM. Overall, 464 patients had tumor size ≤ 5 cm, and 349 had tumor size > 5 cm. The 5-year RFS and OS rates were 38.3% and 61.5% in the ≤ 5 cm group, compared with 25.1% and 59.9% in the > 5 cm group. Long-term survival outcomes were significantly worse as tumor size increased. Multivariate analysis indicated that tumor size > 5 cm was an independent risk factor for tumor recurrence and long-term survival. These results were further confirmed in the PSM cohort of 235 pairs of patients. In cirrhotic patients with solitary HCC and without macrovascular invasion, tumor size may significantly affect the prognosis after curative hepatectomy.

Exonuclease 1 (EXO1), a member of the RAD2 nuclease family, was first described as possessing 5' to 3' nuclease activity and 5' structure-specific endonuclease activity. Here, we show that EXO1 is significantly upregulated in HCC tumor tissues and that high EXO1 expression is significantly correlated with liver cirrhosis. We further demonstrate that EXO1 knockdown decreases proliferation and colony forming abilities of HCC cells in vitro and tumorigenicity in vivo, as well as decreases migration and invasive capabilities of HCC cells. Alternatively, EXO1 overexpression significantly increases the proliferation, colony forming ability, and migration and invasive capabilities of HCC cells in vitro. Additionally, we truncated a region upstream of the transcription start site (TSS) of EXO1 and used the region with the strongest transcriptional activity to predict that the transcription factor FOXP3 can bind to the EXO1 promoter. Bioinformatics analysis found that FOXP3 was positively correlated with EXO1 and luciferase reporter assays and RT-PCR confirmed that FOXP3 could enhance the transcriptional activity of EXO1. CCK-8 assays showed that depletion of FOXP3 further reduces cell proliferation ability after knocking down of EXO1 in vitro. Taken together, our findings indicate that EXO1 acts as an oncogene in HCC and its expression level is related to FOXP3 activity.

Severity of liver cirrhosis is distinct from clinical portal hypertension because there exist different degrees of liver cirrhosis in hepatocellular carcinoma (HCC) patients without significant clinical portal hypertension. Whether severity of cirrhosis affects surgical outcomes for HCC patients in absence of portal hypertension or not remains unclear. This study aims to analyze the effect of cirrhotic severity on surgical outcomes for HCC patients with hepatitis B virus (HBV) infection in absence of portal hypertension. This retrospective study enrolled 166 patients who underwent curative resection for a single HCC ≤5 cm in absence of portal hypertension between February 2011 and December 2013. Liver cirrhosis was sub-classified into no/mild (no/F4A) and moderate/severe (F4B/F4C) according to the Laennec scoring system. The surgical outcomes and complications were analyzed. The surgical mortality was zero in this study. Major complications were apparently higher in the F4B/F4C group than in the no/F4A group (17.0% vs 7.4%, p <0.001). The 1-year, 3-year and 5-year overall survival (OS) rates were 98.5, 88.1 and 80%, respectively, in the no/F4A group, which were significantly higher than those in the F4B/F4C group (98.0, 69.2 and 54.7%, p = 0.001). Microscopic vascular invasion, absence of tumor capsule and severity of liver cirrhosis were independent risk factors of surgical outcomes for HCC patients without portal hypertension. In conclusion, severity of liver cirrhosis affected surgical outcomes for early-stage HCC patients independent of portal hypertension.

Although liver resection (LR) and liver transplantation (LT) are widely considered as potentially curative therapies for selected patients with hepatocellular carcinoma (HCC); however, there is still high risk of tumor recurrence in majority of HCC patients. Previous studies demonstrated that the presence of microvascular invasion (MVI), which was defined as the presence of tumor emboli within the vessels adjacent to HCC, was one of the key factors of early HCC recurrence and poor surgical outcomes after LR or LT. In this review, we evaluated the impact of current MVI status on surgical outcomes after curative therapies and aimed to explore the surgical strategies for HCC based on different MVI status with evidence from pathological examination. Surgical outcomes of HCC patients with MVI have been described as a varied range after curative therapies due to a broad spectrum of current definitions for MVI. Therefore, an international consensus on the validated definition of MVI in HCC is urgently needed to provide a more consistent evaluation and reliable prediction of surgical outcomes for HCC patients after curative treatments. We concluded that MVI should be further sub-classified into MI (microvessel invasion) and MPVI (microscopic portal vein invasion); for HCC patients with MPVI, local R0 resection with a narrow or wide surgical margin will get the same surgical results. However, for HCC patients with MI, local surgical resection with a wide and negative surgical margin will get better surgical outcomes. Nowadays, MVI status can only be reliably confirmed by histopathologic evaluation of surgical specimens, limiting its clinical application. Taken together, preoperative assessment of MVI is of utmost significance for selecting a reasonable surgical modality and greatly improving the surgical outcomes of HCC patients, especially in those with liver cirrhosis.

Liver resection (LR) is the primary treatment method for patients with hepatocellular carcinoma (HCC). Improving surgical safety and reducing surgical morbidity and mortality is important for patients receiving LR. Various devices have been developed to facilitate vascular transection to reduce intraoperative blood loss, which is considered to be a predictor of poor surgical outcomes in patients undergoing LR. Vascular staplers have been widely applied for the division of major vascular and biliary structures in the process of LR; however, when and how to use these tools remains controversial. This review aims to report the rationality and necessity of using vascular staplers in vessel transection during liver surgery. Due to the risk of intraoperative and postoperative hemorrhage and biliary fistula, the process of transection of the portal pedicle and hepatic vein is a crucial step during LR. Stapling represents a vascular dissection technique that is widely used in laparoscopic LR and has then been popularized in open LR. Advocates argue that stapler transection methods provide several advantages, including diminished blood loss, fewer transfusion requirements and shorter operative times. However, other studies have failed to demonstrate those benefits when using these tools compared with the simple clamp-crushing technique. Using the stapler vascular transection method resulted in smaller surgical margins and similar surgical outcomes compared with those of the clamp-crushing vascular transection method. However, the intraoperative use of vascular staplers may significantly increase the financial burden of liver resection for patients with HCC, while not improving short- and long-term outcomes. Therefore, it has been suggested that vascular staplers should not be routinely used in LR. The current review discussed the above points and recommended that the stapling transection of the portal pedicle and hepatic vein should be applied during laparoscopic LR in a rational manner. However, the suturing ligation method should be routinely used in open LR.

Background: Inflammatory Pseudo Tumor (IPT)-like Follicular Dendritic Cell (FDC) Sarcoma of the liver is a very rare disease and occurs mostly in the lymph nodes. Till now, only 19 cases were reported in the English literature. However, the coexistence of IPT-like Sarcoma and Non-Hodgkin’s Lymphoma(NHL) in the same patient has never been reported.Case presentation: We reported a case of a 47-year-old male patient who had a history of Hepatitis B virus (HBV) infection and presented with right upper abdominal discomfort. Nineteen years ago, he underwent liver resection of segment VII for Hepatic Non-Hodgkin Lymphoma (B-cell lymphoma). Serum alpha fetoprotein (AFP) level was normal. However, Imaging studies revealed a well-circumscribed, solid mass in the right hepatic lobe and was diagnosed as (Hepatocellular Carcinoma) HCC or Hepatic Lymphoma preoperatively. Right hemi-hepatectomy was performed on this patient. Histological report showed features of a mixture of chronic inflammatory cells and variable amounts of spindle cells. Also, Immuno-Histo-Chemical (IHC) studies demonstrated that all the tumor cells showed strong nuclear in situ labeling for EBV-encoded small RNAs (EBER) and strongly positive stainings with CD21 and CD35. The patient is still disease free after a follow-up of 40 months. Conclusions: To our knowledge, this is the first report demonstrating Hepatic IPT-like FDC Sarcoma in a patient with Primary Hepatic Non-Hodgkin Lymphoma history. In regards to treatment, complete surgical resection should be performed and would acquire excellent long-term outcomes.

Background Evaluating cirrhotic severity is essential for individualizing surgical modalities for patients with hepatocellular carcinoma (HCC). Our previous study proposed a non-invasive method named cirrhotic severity scoring (CSS) to stage liver cirrhosis. Indocyanine green retention rate at 15 min (ICG-R15) has been widely used for the preoperative evaluation of hepatic functional reserve; however, whether ICG-R15 is well correlated with cirrhotic severity, and especially whether comparable with CSS in predicting cirrhotic severity in HCC patients with Child-Pugh grade A liver function remains unknown. Methods Overall, 510 HCC patients with Child-Pugh grade A liver function undergoing hepatectomy between January 2011 and December 2014 were retrospectively studied. Cirrhotic severity was pathologically assessed using the Laennec staging system. The correlations between ICG-R15, CSS, and cirrhotic severity were analyzed. Furthermore, the performance of ICG-R15 and CSS in predicting posthepatectomy liver failure (PHLF) and 90-day mortality was compared. Results Patients with no, mild, moderate, and severe cirrhosis accounted for 15.9%, 29.2%, 35.9%, and 19.0%, respectively, in the entire cohort. ICG-R15 was found to be less than 10% in 100%, 93.3%, 86.3%, and 70.1% of the patients with no, mild, moderate, and severe cirrhosis, respectively. There was only a weak correlation between ICG-R15 and the pathological severity of liver cirrhosis (r = 0.325; P < 0.001). However, CSS showed a strong correlation with the pathological severity of liver cirrhosis (r = 0.788; P < 0.001). For those with ICG-R15 in the normal range, the accuracy of CSS in diagnosing no/mild, moderate, and severe cirrhosis was 89.1%, 72.8%, and 72.1%, respectively. In addition, CSS was superior to ICG-R15 in predicting PHLF and 90-day mortality. Conclusions CSS was more useful than ICG-R15 in the preoperative assessment of cirrhotic severity in HCC patients with Child-Pugh grade A liver function. More studies are needed to further validate CSS in patients with different Child-Pugh grades.

Rationale: Hepatic inflammatory pseudotumor (IPT)-like follicular dendritic cell (FDC) sarcoma is a very rare disease. Till now, only 19 cases were reported in the English literature. However, the coexistence of IPT-like sarcoma and non-Hodgkin lymphoma (NHL) in the same patient has never been reported. In this report, we presented a case of hepatic IPT-like FDC with hepatic NHL history of which both were successfully resected. Patient concerns: We reported a case of a 47-year-old male patient who presented with right upper abdominal discomfort. Nineteen years ago, he underwent liver resection of segment VII for hepatic NHL (B-cell lymphoma). He had a history of chronic hepatitis B virus infection. Serum alpha fetoprotein level was normal. However, imaging studies revealed a well-circumscribed, solid mass in the right hepatic lobe, he came back to the clinic because he was worried about a recurrence of the B-cell lymphoma. Diagnoses: Based on the patient's past medical history and magnetic resonance imaging results, and he was diagnosed as hepatocellular carcinoma or hepatic NHL preoperatively. Interventions: Right hemi-hepatectomy was performed on this patient. Outcomes: Histological report showed features of a mixture of chronic inflammatory cells and variable amounts of spindle cells. Also, immuno-histo-chemical studies demonstrated that all the tumor cells showed strong nuclear in situ labeling for EBV-encoded small RNAs and strongly positive stainings with CD21 and CD35. The patient tolerated the surgery well, recovered smoothly and he was discharged on postoperative day 7 (day 7). The patient is still disease free after a follow-up of over 50 months. Conclusions: To our knowledge, this is the first report demonstrating hepatic IPT-like FDC sarcoma in a patient with primary hepatic NHL history. In regards to treatment, complete surgical resection should be performed and would acquire excellent long-term outcomes.

Numerous studies have suggested that microRNAs (miRNAs) potently affect hepatocarcinogenesis. However, the miRNA expression profiling in patients with hepatocellular carcinoma (HCC) of familial aggregation and hepatitis B virus (HBV) infection has not been elucidated. In the present study, the plasma miRNA expression profiles of 3 patients with HCC with familial aggregation of HCC and HBV infection and 1 healthy volunteer were examined by microarray analysis, in order to identify relevant miRNAs involved in the pathogenesis of HCC with familial aggregation and HBV infection. The results indicated that 26 miRNAs exhibited a ≥20-fold increase or decrease in the plasma of patients with HCC, compared with the healthy control (24 upregulated and 2 downregulated). Among these altered miRNAs, 15 of them have been reported in HCC. The other 11 miRNAs have never been reported in HCC. These differentially-expressed miRNAs may be potential molecular markers for HCC pathogenesis and development.

Liver resection is the mainstay of treatment for patients with hepatocellular carcinoma and compensated cirrhosis. We investigated the relationship between the morphologic severity of cirrhosis and post-hepatectomy liver failure (PHLF) and evaluated the role of cirrhosis staging in determination of the extent limit for liver resection.The clinicopathologic data of 672 consecutive patients with Child-Pugh grade A liver function who underwent curative liver resection for hepatocellular carcinoma in Tongji Hospital from 2009 to 2013 were retrospectively reviewed. Severity of cirrhosis was staged morphologically and histologically. Risk factors for histologic cirrhosis and PHLF were analyzed. The extent limit of liver resection with reference to morphologic staging was studied.Morphologic and histologic stages were significantly correlated (τ = 0.809, P0.001). Multivariate analysis showed that morphologic staging was the most crucial factor for histologic cirrhosis (odds ratio = 26.99, 95% confidence interval = 16.88-43.14, P0.001) and PHLF (odds ratio = 11.48, 95% confidence interval = 6.04-21.82, P0.001). The incidence of PHLF was high in patients with mild cirrhosis after resection of four or more liver segments (13.6%), those with moderate cirrhosis after major resection (38.1%), and those with severe cirrhosis or severe portal hypertension after resection of two or more liver segments (63.2% and 50.0%, respectively).Morphologic severity of cirrhosis is an independent predictor of PHLF. Resection of fewer than four liver segments is justified in patients with mild cirrhosis. Major resection is not recommended in patients with moderate cirrhosis. In patients with severe cirrhosis or severe portal hypertension, only resection of fewer than two liver segments can be safely performed.

Background The optimum operative treatment for early hepatocellular carcinoma (HCC) in patients with compensated liver function remains controversial. This study aimed to assess the impact of the severity of cirrhosis on survival after liver resection (LR) and to determine the importance of the severity of cirrhosis in operative decision-making for early HCC. Methods The records of 307 patients with HCC with a solitary tumor ≤5 cm undergoing either LR or liver transplantation (LT) were reviewed retrospectively. The Child–Pugh class A patients in the LR group were stratified according to the severity of cirrhosis. Survival of each subgroup was compared with that of the LT group. Results Both the recurrence-free survival (RFS) and disease-specific survival (DSS) in the LR group were worse than those in the LT group. Stratification of the Child A patients in the LR group yielded 5-year RFS and DSS rates of 71% and 86%, respectively, for the cirrhosis-free subgroup, 58% and 79% for the mild cirrhosis subgroup, and 25% and 45% for the moderate/severe cirrhosis subgroup. There were no differences in the rates of RFS and DSS between either the cirrhosis-free or mild cirrhosis subgroup and the LT group, whereas the subgroup with moderate/severe cirrhosis had poorer RFS and DSS rates than the LT group. Conclusion LR is the best treatment for early HCC in patients without cirrhosis or with mild cirrhosis and compensated liver function, whereas LT is recommended for those with moderate/severe cirrhosis, even if their liver function is well compensated.

Using only catalytic amounts of alkyl halides in the reactions of poor nucleophilic amines/amides and alcohols led to a selective Hofmann N-alkylation reaction catalytic in alkyl halides, providing a practical and efficient method for the practical synthesis of mono- or di-alkylated amines/amides in high selectivities. This new method avoids the use of large amounts of bases, alkyl halides, and solvents, and generates water as the only byproduct. Preliminary mechanistic studies showed that alkyl halides are key intermediates/catalysts regeneratable in the reaction cycle.

Poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors and histone deacetylase (HDAC) inhibitors have recently emerged as promising anticancer drugs. The aim of this study was to investigate the effect of combination treatment with the PARP inhibitor PJ34 and HDAC inhibitor SAHA on the proliferation of liver cancer cells. Cell proliferation and apoptosis were assessed in three human liver cancer cell lines (HepG2, Hep3B and HCC-LM3) treated with PJ34 (8 μmol/L) and SAHA (1 μmol/L), alone or combined, by Cell Counting Kit-8 assay and flow cytometry, respectively. The nude mice bearing subcutaneous HepG2 tumors were administered different groups of drugs (10 mg/kg PJ34, 25 mg/kg SAHA, 10 mg/kg PJ34+25 mg/kg SAHA), and the inhibition rates of tumor growth were compared between groups. The results showed that combined use of PJ34 and SAHA could synergistically inhibit the proliferation of liver cancer cell lines HepG2, Hep3B and HCC-LM3. The apoptosis rate of HepG2 cells treated with PJ34+SAHA was significantly higher than that of HepG2 cells treated with PJ34 or SAHA alone (P

Minocycline, a semisynthetic tetracycline, is a highly lipophilic molecule capable of infiltrating tissues and blood. Previous studies have revealed the functions and mechanisms of minocycline in anti-inflammation, protection of the nervous system and certain tumors. The role of minocycline has never been investigated in hepatocellular carcinoma (HCC). The functions of minocycline on HCC cells were investigated using immunohistochemical staining and western blotting. Minocycline was applied to L02, HepG2 and Huh7 cells, and the growth characteristics were studied. Cisplatin was administered in combination with minocycline in this study. Cell cycle and apoptosis analyses were employed to investigate the mechanisms underlying the growth regulation associated with minocycline and(or) cisplatin. Minocycline caused S phase cell cycle arrest and an increase in the apoptotic rate associated with upregulation of p27, cleaved-caspase8, cleaved-caspase3 and cleaved-PRAP-1. Low dose of cisplatin promoted cell cycle arrest and apoptosis, whereas minocycline was mainly associated with upregulation of cleaved-PARP-1. The combination of cisplatin and minocycline increased the rate and extent of cell cycle arrest and increased the apoptosis rate caused by minocycline. A novel mechanism was revealed. Minocycline functions as an antitumor drug in HCC by regulating p27, caspase-3 and PARP-1. Cisplatin enhanced minocycline's effect on PARP-1.

Abundant and cheap iron readily catalyzed the aerobic oxidative reactions of primary amines, secondary amines, benzylamines with anilines, and alcohols with amines by directly using air as the economic and safe oxidant, providing several direct, practical, and greener approaches for the preparation of useful imines.

Using only catalytic amounts of alkyl halides in the reactions of poor nucleophilic amines/amides and alcohols led to a selective Hofmann N-alkylation reaction catalytic in alkyl halides, providing a practical and efficient method for the practical synthesis of mono- or di-alkylated amines/amides in high selectivities. This new method avoids the use of large amounts of bases, alkyl halides, and solvents, and generates water as the only byproduct. Preliminary mechanistic studies showed that alkyl halides are key intermediates/catalysts regeneratable in the reaction cycle.

Rationale Portal vein thrombosis is defined as any thrombosis that develops in the portal vein system. It is considered a very rare and extremely lethal complication of hepatopancreatobiliary surgery. Patient concerns Acute portal vein thrombosis after hepatectomy in patients with hepatolithiasisis very rare. Acute portal vein thrombosis is considered as a dangerous complication after hepatectomy. It is easy to ignore the symptom of acute portal vein thrombosis. Once the appropriate time of treatment is past, it would lead to patients' death. Diagnose Acute portal vein thrombosis after hepatectomy in a patient with hepatolithiasis INTERVENTIONS:: We consider anticoagulation therapy and percutaneous transhepatic portal vein puncture and thrombectomy once the diagnosis of acute portal vein thrombosis is confirmed. Outcomes The patient's liver function continued to deteriorate, eventually resulting in death. Lessons Acute portal vein thrombosis after hepatectomy is difficult to diagnose. The management of acute portal vein thrombosis remains controversial according to its severity, location or time of discovering.

Background Severity of liver cirrhosis plays a vital role in determining an appropriate surgical strategy for HCC treatment. However, preoperative evaluation of the severity of cirrhosis has not been established in a surgical setting. This study aims to develop a model to predict the severity of cirrhosis. Methods Overall, 604 patients with hepatocellular carcinoma (HCC) and hepatitis B virus–related cirrhosis undergoing liver resection from Jan 2005 to Jun 2013 were randomly divided into either the model building group ( n = 304) or the test group ( n = 300). The severity of cirrhosis of the resected specimens was pathologically staged according to the Laennec scoring system, which sub-classified cirrhosis into either stage F4A, F4B, or F4C. Results A logistic regression analysis showed that varicosity, portal vein diameter, spleen thickness, and platelet count were significantly associated with the histologic sub-classification of cirrhosis in the model building group. Based on these four parameters, a scoring model for predicting the severity of cirrhosis was established. The model was then verified in the test group, the areas under the ROC (AUROC) for predicting mild (F4A), moderate (F4B), and severe cirrhosis (F4C) were 0.861 (95% confidence interval [CI], 0.810-0.911), 0.860 (95% CI, 0.819-0.901), and 0.968 (95% CI, 0.951-0.985), respectively. The accuracy of this model in predicting mild, moderate, and severe cirrhosis is 79.3%, 81.0%, and 85.3%, respectively. Conclusions By using this model, the severity of cirrhosis can be reliably staged preoperatively, which will provide more information on cirrhotic livers in surgical settings for the treatment of hepatitis B virus–related HCC.

Background: 1-methylpropyl 2-imidazolyl disulfide (PX-12), a thioredoxin 1 (Trx1) inhibitor, has been investigated in a number of ancers, but its effectiveness in the treatment of hepatocellular carcinoma (HCC) has not been reported. PX-12 has generated considerable interest in its use in a variety of solid tumors, yet most studies have confined their interests to using PX-12 as a single agent. The aim of this study is to investigate whether PX-12 inhibits cell growth and has a synergistic anti-tumor effect in combination with 5-fluorouracil (5-FU) in HCC. Methods: Cells were treated with different concentrations of PX-12 and 5-FU. Cell viability assays, colony formation assay, cell cycle assay, reactive oxygen species (ROS) assay, apoptosis analysis, western blot assay, immunohistochemistry and xenograft tumorigenicity assay were performed. Results: Treatment with PX-12 inhibited cell growth, induced S-phase arrest, and increased ROS levels. PX-12-induced apoptosis and inhibition of colony formation were associated with the generation of ROS, and inhibition of ROS attenuated PX-12-induced apoptosis and inhibition of colony formation. Treatment with PX-12 increased the expression of bax and reduced the expression of bcl-2, indicating that PX-12-mediated apoptosis is mitochondria-dependent. PX-12 also exerted a synergistic effect with 5-FU tosignificantly suppress tumorigenicity both in vitro and in vivo. Inhibition of ROS accumulation reduced the synergistic effect of PX-12 and 5-FU. Conclusions: PX-12 has anti-tumor activity and a synergistic effect in combination with 5-FU in HCC. Treatment with PX-12 alone or in combination with 5-FU may have clinical use in the treatment of HCC and other cancers.

Rupture of hepatocellular carcinoma (HCC) releases tumor cells and furthers peritoneal metastasis. The present study investigated the killing effects of distilled water (DW) on HCC cells and the clinical outcomes of patients undergoing liver resection with DW lavage for spontaneously ruptured HCC. Human HCC cells (BEL-7402, SMMC7721) were treated with DW, the morphological changes observed, and cell viability measured. DW-treated HCC cells were also injected intraperitoneally into nude mice, and the formation of tumor nodules and overall survival (OS) measured. The clinicopathological data of 141 consecutive patients undergoing liver resection for spontaneously ruptured HCC during 1998–2011 were retrospectively reviewed. Fifteen minutes of DW exposure caused complete cell lysis of HCC cells in vitro and completely prevented tumor formation and prolonged survival time in nude mice. Among the 141 patients, the 1-, 3-, and 5-year disease-free survival (DFS) and OS rates in patients administered DW lavage during surgery were 68.9, 24.6, and 6.6 %, respectively, and 95.1, 65.1, and 40 %, respectively, which were significantly higher than those in patients who did not (P

Hepatocellular carcinoma is the third leading cause of cancer-related death in the world, and cirrhosis is the main cause of hepatocellular carcinoma and adversely affects surgical outcomes. Liver resection, liver transplantation, and local ablation are potentially curative therapies for early hepatocellular carcinoma (HCC). There exists an obvious histological variability of severity within cirrhosis which has different clinical stages. For patients with Child-Pugh B cirrhosis and/or portal hypertension and HCC within Milan criteria, consensus guidelines suggest that liver transplantation is the best treatment of choice; liver resection is widely accepted as first-line treatment for patients with early-stage HCC and preserved liver function; and local ablation is the treatment of choice in patients with small tumors who are not candidates for surgery or can be used as a temporary treatment during the waiting period for transplantation. For patients with compensated cirrhosis or Child A cirrhosis, the selection of surgical modality based on subclassification of cirrhosis remains unclear. This review examines the current status of the selection of surgical modality for hepatocellular carcinoma treatment in cirrhotic patients and aims to emphasize the effects of the severity of cirrhosis on the selection of surgical modality for the treatment of hepatocellular carcinoma.

Abundant and cheap iron readily catalyzed the aerobic oxidative reactions of primary amines, secondary amines, benzylamines with anilines, and alcohols with amines by directly using air as the economic and safe oxidant, providing several direct, practical, and greener approaches for the preparation of useful imines.