Development of preoperative prognostic models including radiological features for survival of singular nodular HCC patients.

BACKGROUND: Early singular nodular hepatocellular carcinoma (HCC) is an ideal surgical indication in clinical practice. However, almost half of the patients have tumor recurrence, and there is no reliable prognostic prediction tool. Besides, it is unclear whether preoperative neoadjuvant therapy is necessary for patients with early singular nodular HCC and which patient needs it. It is critical to identify the patients with high risk of recurrence and to treat these patients preoperatively with neoadjuvant therapy and thus, to improve the outcomes of these patients. The present study aimed to develop two prognostic models to preoperatively predict the recurrence-free survival (RFS) and overall survival (OS) in patients with singular nodular HCC by integrating the clinical data and radiological features. METHODS: We retrospective recruited 211 patients with singular nodular HCC from December 2009 to January 2019 at Eastern Hepatobiliary Surgery Hospital (EHBH). They all met the surgical indications and underwent radical resection. We randomly divided the patients into the training cohort (n =132) and the validation cohort (n = 79). We established and validated multivariate Cox proportional hazard models by the preoperative clinicopathologic factors and radiological features for association with RFS and OS. By analyzing the receiver operating characteristic (ROC) curve, the discrimination accuracy of the models was compared with that of the traditional predictive models. RESULTS: Our RFS model was based on HBV-DNA score, cirrhosis, tumor diameter and tumor capsule in imaging. RFS nomogram had fine calibration and discrimination capabilities, with a C-index of 0.74 (95% CI: 0.68-0.80). The OS nomogram, based on cirrhosis, tumor diameter and tumor capsule in imaging, had fine calibration and discrimination capabilities, with a C-index of 0.81 (95% CI: 0.74-0.87). The area under the receiver operating characteristic curve (AUC) of our model was larger than that of traditional liver cancer staging system, Korea model and Nomograms in Hepatectomy Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma, indicating better discrimination capability. According to the models, we fitted the linear prediction equations. These results were validated in the validation cohort. CONCLUSIONS: Compared with previous radiography model, the new-developed predictive model was concise and applicable to predict the postoperative survival of patients with singular nodular HCC. Our models may preoperatively identify patients with high risk of recurrence. These patients may benefit from neoadjuvant therapy which may improve the patients' outcomes.

Circulating Tumor Cells Expressing Krüppel-Like Factor 8 and Vimentin as Predictors of Poor Prognosis in Pancreatic Cancer Patients.

BACKGROUND: Circulating tumor cells (CTCs) with an epithelial-mesenchymal transition phenotype in peripheral blood may be a useful marker of carcinomas with poor prognosis. The aim of this study was to determine the prognostic significance of CTCs expressing Krüppel-like factor 8 (KLF8) and vimentin in pancreatic cancer (PC). METHODS: CTCs were isolated by immunomagnetic separation from the peripheral blood of 40 PC patients before undergoing surgical resection. Immunocytochemistry was performed to identify KLF8+ and vimentin+ CTCs. The associations between CTCs and time to recurrence (TTR), clinicopathologic factors, and survival were assessed. Univariate and multivariate analyzes were performed to identify risk factors. RESULTS: Patients with CTCs (n = 30) had a higher relapse rate compared to those without (n = 10) (70.0% vs 20.0%; P < 0.01). The proportion of KLF8+/vimentin+ CTCs to total CTCs was inversely related to TTR (r = -0.646; P < 0.01); TTR was reduced in patients with > 50% of CTCs identified as KLF8+/vimentin+ (P < 0.01). Independent risk factors for recurrence were perineural invasion and > 50% KLF8+/vimentin+ CTCs (both P < 0.05). CONCLUSION: Poor prognosis can be predicted in PC patients when > 50% of CTCs are positive for KLF8 and vimentin.

Antiviral Therapy Reduces Hepatocellular Carcinoma Recurrence in Patients With Low HBV-DNA Levels: A Randomized Controlled Trial.

BACKGROUND: Despite antiviral treatment has been shown to reduce hepatocellular carcinoma (HCC) recurrence after curative treatment for hepatitis B virus (HBV)-related HCC in patients with high preoperative HBV-DNA levels, it is still unclear whether antiviral therapy is useful in reducing recurrence in patients with low preoperative HBV-DNA levels. METHODS: In this randomized controlled trial, 200 patients who underwent curative resection for HCC with low baseline HBV-DNA levels were randomly assigned to receive preemptive antiviral therapy or not. The primary endpoints were recurrence-free survival. This study was censored on March 31, 2015 when all surviving patients had a minimum follow-up of 60 months. The analysis was done on an intention-to-treat basis. RESULTS: The baseline clinical, laboratory, and tumor characteristics of the 2 groups were comparable. The 1-, 3-, and 5-year recurrence-free survival rates for the antiviral group and the control group were 85.9%, 55.2%, and 52.0% and 80.6%, 40.9%, and 32.3%, respectively. The corresponding overall survival rates for the 2 groups were 94.0%, 75.7%, and 64.1% and 90.0%, 62.4%, and 43.7%, respectively. The recurrence-free survival and overall survival for the antiviral group were significantly better than the control group (P = 0.016, P = 0.004, respectively). After adjusting for confounding prognostic factors in a Cox model, the relative risks of recurrence and death for antiviral treatment were 0.601 [95% confidence interval (CI), 0.409-0.884; P = 0.010] and 0.509 (95% CI, 0.333-0.778; P = 0.002), respectively. Antiviral therapy was an independent protective factor of late tumor recurrence (hazard ratio [HR] = 0.316, 95% CI 0.157-0.637; P = 0.001) but not of early tumor recurrence (HR = 0.782, 95% CI, 0.493-1.240; P = 0.296). CONCLUSIONS: In patients with low preoperative HBV-DNA levels, antiviral therapy significantly reduced HCC recurrence after R0 hepatic resection.

Antiviral therapy improves postoperative survival in patients with hepatocellular carcinoma: a randomized controlled trial.

OBJECTIVE: A randomized controlled trial was conducted to find out whether antiviral therapy in patients with hepatitis B-related hepatocellular carcinoma (HCC) improves long-term survival after hepatic resection. BACKGROUND: Despite advances in surgery and in multidisciplinary treatment, there is still no effective adjuvant treatment to prevent HCC recurrence after R0 resection for HCC. Whether antiviral therapy is useful in reducing postoperative HCC recurrence is unclear. METHODS: Between May 2007 and April 2008, patients who received R0 hepatic resection for HBV-related HCC were randomly assigned to receive no treatment (the control group, n = 100) or antiviral therapy (adefovir 10 mg/d, the antiviral group, n = 100). RESULTS: The baseline clinical, laboratory, and tumor characteristics of the 2 groups were comparable. The 1-, 3-, and 5-year recurrence-free survival rates for the antiviral group and the control group were 85.0%, 50.3%, 46.1% and 84.0%, 37.9%, 27.1%, respectively. The corresponding overall survival rates for the 2 groups were 96.0%, 77.6%, 63.1% and 94.0%, 67.4%, 41.5%, respectively. The recurrence-free survival and overall survival for the antiviral group were significantly better than the control group (P = 0.026, P = 0.001). After adjusting for the confounding prognostic factors in a Cox model, the relative risks of recurrence and death for antiviral treatment were 0.651 [95% confidence interval (CI): 0.451-0.938; P = 0.021] and 0.420 (95% CI: 0.271-0.651; P < 0.001). Antiviral therapy was an independent protective factor of late tumor recurrence (HR = 0.348, 95% CI: 0.177-0.687; P = 0.002) but not of early tumor recurrence [hazard ratio (HR) = 0.949, 95% CI: 0.617-1.459; P = 0.810]. CONCLUSIONS: In patients with hepatitis B-related HCC, adefovir antiviral therapy reduced late HCC recurrence and significantly improved overall survival after R0 hepatic resection.

Partial hepatectomy vs. transcatheter arterial chemoembolization for resectable multiple hepatocellular carcinoma beyond Milan Criteria: a RCT.

BACKGROUND & AIMS: The aim of this randomized comparative trial (RCT) is to compare partial hepatectomy (PH) with transcatheter arterial chemoembolization (TACE) to treat patients with resectable multiple hepatocellular carcinoma (RMHCC) outside of Milan Criteria. METHODS: This RCT was conducted on 173 patients with RMHCC outside of Milan Criteria (a solitary tumor up to 5 cm or multiple tumors up to 3 in number and up to 3 cm for each tumor) who were treated in our centre from November 2008 to September 2010. The patients were randomly assigned to the PH group or the TACE group. The primary outcome measure was overall survival (OS) from the date of treatment. A multivariate Cox proportional hazards regression analysis was performed to assess the prognostic risk factors associated with OS. RESULTS: The 1-, 2-, and 3-year OS rates were 76.1%, 63.5%, and 51.5%, respectively, for the PH group compared with 51.8%, 34.8%, and 18.1%, respectively, for the TACE group (Log-rank test, χ(2)=24.246, p<0.001). Multivariate Cox proportional hazards regression analysis revealed the type of treatment (hazard ratio, 0.434; 95% CI, 0.293 to 0.644, p<0.001), number of tumor (hazard ratio, 1.758; 95% CI, 1.213 to 2.548, p=0.003) and gender (hazard ratio, 0.451; 95% CI, 0.236 to 0.862, p=0.016) were significant independent risk factors associated with OS. CONCLUSIONS: PH provided better OS for patients with RMHCC outside of Milan Criteria than conventional TACE. The number of tumor and gender were also independent risk factors associated with OS for RMHCC.

The histone acetyltransferase hMOF suppresses hepatocellular carcinoma growth.

Males absent on the first (MOF) is a histone acetyltransferase belongs to the MYST (MOZ, Ybf2/Sas3, Sas2 and TIP60) family. In mammals, MOF plays critical roles in transcription activation by acetylating histone H4K16, a prevalent mark associated with chromatin decondensation. MOF can also acetylate transcription factor p53 on K120, which is important for activation of pro-apoptotic genes; and TIP5, the largest subunit of NoRC, on K633. However, the role of hMOF in hepatocellular carcinoma remains unknown. Here we find that the expression of hMOF is significantly down-regulated in human hepatocellular carcinoma and cell lines. Furthermore, our survival analysis indicates that low hMOF expression predicts poor overall and disease-free survival. We demonstrate that hMOF knockdown promotes hepatocellular carcinoma growth in vitro and in vivo, while hMOF overexpression reduces hepatocellular carcinoma growth in vitro and in vivo. Mechanically, we show that hMOF regulates the expression of SIRT6 and its downstream genes. In summary, our findings demonstrate that hMOF participates in human hepatocellular carcinoma by targeting SIRT6, and hMOF activators may serve as potential drug candidates for hepatocellular carcinoma therapy.

Preoperative hepatitis B virus DNA level is a risk factor for postoperative liver failure in patients who underwent partial hepatectomy for hepatitis B-related hepatocellular carcinoma.

OBJECTIVE: Our objective was to explore the short-term effects of preoperative serum hepatitis B virus DNA level (HBV DNA) on postoperative hepatic function in patients who underwent partial hepatectomy for hepatitis B-related hepatocellular carcinoma (HCC). METHODS: The clinical data of 1,602 patients with hepatitis B-related HCC who underwent partial hepatectomy in our department were retrospectively studied. The patients were divided into three groups according to their preoperative HBV DNA levels: group A <200 IU/mL, group B 200-20,000 IU/mL, and group C >20,000 IU/mL. The rates of postoperative complications, especially the rate of postoperative liver failure, were compared. RESULTS: There were significant differences among the three groups in the rates of postoperative liver failure. On multivariate logistic regression analysis, a high preoperative HBV DNA level was an independent risk factor for postoperative liver failure. CONCLUSIONS: Preoperative HBV DNA level was a significant risk factor for postoperative hepatic dysfunction.

Posthepatectomy HBV reactivation in hepatitis B-related hepatocellular carcinoma influences postoperative survival in patients with preoperative low HBV-DNA levels.

OBJECTIVE: This study aimed to clarify the incidence of hepatitis B virus (HBV) reactivation and its significance on long-term survival after partial hepatectomy in patients with HBV-related hepatocellular carcinoma (HCC), who had preoperative low HBV-DNA level of less than 2000 IU/mL. BACKGROUND: HBV reactivation is a frequent complication of systemic chemotherapy in hepatitis B surface antigen-positive patients. Surgery and anesthesia result in a generalized state of immunosuppression in the immediate postoperative period. Data on HBV reactivation and its significance after partial hepatectomy are unclear. PATIENTS AND METHODS: Consecutive patients from January 2006 to December 2007 were retrospectively studied. RESULTS: HBV reactivation happened in 19.1% of patients in 1 year. There were 28 patients whose HBV reactivation was detected after the diagnosis of HCC recurrence. On multivariate analysis, hepatitis B e antigen (HBeAg) positivity, preoperative HBV-DNA above the lower limit of quantification (≥200 IU/mL), Ishak inflammation score of greater than 3, preoperative transarterial chemoembolization (TACE), operation time of more than 180 minutes, blood transfusion, and without prophylactic antiviral therapy were significantly associated with an increased risk of HBV reactivation. HBV reactivation negatively influenced postoperative hepatic functions. The posthepatectomy liver failure rate in patients with HBV reactivation was significantly higher than in those without reactivation (11.8% vs 6.4%; P = 0.002). The 3-year disease-free survival (DFS) rate and overall survival (OS) rates after resection in patients with HBV reactivation were significantly lower than those without reactivation (34.1% vs 46.0%; P = 0.009, and 51.6% vs 67.2%; P < 0.001, respectively). HBeAg positivity, detectable preoperative HBV-DNA level, high Ishak inflammation score, preoperative TACE, long operation time, and blood transfusion were independent risk factors for HBV reactivation, whereas prophylactic antiviral therapy was a protective factor. HBV reactivation, HBeAg positivity, HBV-DNA level of 200 IU/mL or more, tumor diameter greater than 5 cm, presence of satellite nodules, presence of portal vein tumor thrombus, blood transfusion, and resection margin less than 1.0 cm were independent risk factors for DFS. A HBV-DNA level of 200 IU/mL or more, an Ishak fibrosis score of 4 or greater, a tumor diameter greater than 5 cm, the presence of satellite nodules, the presence of portal vein tumor thrombus, a resection margin less than 1.0 cm, no prophylactic antiviral therapy, and HBV reactivation were independent risk factors for OS. CONCLUSIONS: HBV reactivation was common after partial hepatectomy for HBV-related HCC with a preoperative low HBV-DNA level of less than 2000 IU/mL. Routine prophylactic antiviral treatment should be given before partial hepatectomy.

Early viral suppression predicts good postoperative survivals in patients with hepatocellular carcinoma with a high baseline HBV-DNA load.

PURPOSE: To correlate early HBV-DNA suppression by antiviral treatment with posthepatectomy long-term survivals in patients with HBV-related hepatocellular carcinoma (HCC). METHODS: A retrospective study was conducted on patients with a baseline HBV-DNA load of >2,000 IU/ml. The cumulative rates of HBV-DNA undetectability at weeks 24 and 48, as well as long-term tumor recurrence and overall survivals were determined. RESULTS: Of 1,040 patients with a high baseline HBV-DNA load, 865 patients received antiviral treatment. At a median follow-up of 42 months, 616 patients (59.2 %) had developed HCC recurrence and 482 patients (46.3 %) had died. The median time to recurrence was 25 months. In patients who received antiviral treatment, the cumulative rates of HBV-DNA undetectability (<200 IU/ml) were 54.3 and 88.1 % at weeks 24 and 48, respectively. There was no significant difference between the two groups of patients who received antiviral treatment or not for disease-free survival. On multivariate analyses, tumor size >5 cm, blood transfusion, surgical margin <1 cm, presence of satellite nodules, presence of portal vein tumor thrombus and high Ishak inflammation score were significant risk factors of HCC recurrence. Also, tumor size >5 cm, surgical margin <1 cm, presence of satellite nodules, presence of portal vein tumor thrombus and high Ishak fibrosis score were significant factors associated with poor postoperative overall survival. On the other hand, an undetectable HBV-DNA level before week 24 was a significant protective factor of disease-free survival and overall survival. CONCLUSIONS: Early HBV-DNA suppression with antiviral treatment improved prognosis of patients with HBV-related HCC.

Prognostic Analysis of Single Large Hepatocellular Carcinoma Following Radical Resection: A Single-Center Study.

Objective: To investigate the survival and independent prognostic factors for single large hepatocellular carcinoma (SLHCC) after surgical resection. Methods: Patients with SLHCC who underwent radical resection from January 2013 to December 2017 were retrospectively analyzed. The Kaplan-Meier method was used to analyze the overall survival (OS) rate and recurrence-free survival (RFS) rates. Cox forward stepwise regression was performed to analyze the independent prognostic factors. Results: A total of 485 cases were included. The average age was 51.2±11.2 years, 88.9% had a history of hepatitis B virus infection, and most patients had normal liver function. The average tumor diameter was 8.8±3.0 cm. The 1-, 3-, and 5-year OS and RFS rates were 76.8%, 56.7%, and 45.7%, and 61.0%, 46.2%, and 34.7%, respectively. Multivariate analysis showed that liver cirrhosis (HR=1.456, P=0.004), total bilirubin (TB) ≥17.1 µmol/L (HR=1.437, P=0.011), glutamyl transferase (GGT) >60 U/L (HR=1.438, P=0.020), lactate dehydrogenase (LDH) >225 U/L (HR=1.442, P=0.007), blood loss ≥400 mL (HR=1.339, P=0.027), microvascular invasion (MVI) (HR=1.492, P=0.004), satellite lesions (HR=1.859, P<0.0001) and Edmondson-Steiner grade III+IV (HR=1.740, P=0.018) were independent risk factors for reduced OS in SLHCC patients. Sex (HR=1.763, P=0.003), liver cirrhosis (HR=1.382, P=0.007), GGT >60 U/L (HR=1.512, P=0.003), LDH >225 U/L (HR=1.480, P=0.002), MVI (HR=1.545, P=0.001), and satellite lesions (HR=1.564, P=0.001) were independent risk factors for reduced RFS. OS and RFS nomograms were constructed using risk factors with C-index values of 0.692 (95% CI: 0.659-0.724) and 0.659 (95% CI: 0.623-0.693), respectively. The Hosmer-Leme test demonstrated the good fit of both nomograms. Conclusion: Surgical resection is the standard and effective treatment for SLHCC patients. Sex, liver cirrhosis, TB≥17.1 µmol/L, GGT>60 U/L, LDH>225 U/L, blood loss≥400 mL, MVI, Edmondson-Steiner grade III+IV, and satellite lesions were found to be independent prognostic factors in SLHCC patients following radical resection. The OS and RFS nomograms accurately predicted the prognosis of SLHCC patients.

Efficacy and safety of Lenvatinib-based combination therapies for patients with unresectable hepatocellular carcinoma: a single center retrospective study.

Background: Reports on Lenvatinib-based therapies show promising treatment outcomes for patients with unresectable hepatocellular carcinoma (uHCC). However, the effect and safety of Lenvatinib-based therapies still need to be further studies. Methods: This was a retrospective, single-center study on the safety and treatment efficacy of Lenvatinib-based combination therapies for uHCC Patients. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The secondary endpoints were progressive disease (PD), stable disease (SD), partial response (PR), and complete response (CR). Results: Of 91 patients, there were 16 females and 75 males with uHCC who received systemic therapies based on Lenvatinib in our center. Forty-six patients (50.5%) received Lenvatinib combined with PD-1 antibody treatment. All these patients also received local therapy with the exception of 2 patients. The remaining 36 patinets received Lenvatinib combined with transcatheter arterial chemoembolization (TACE), 1 patient treated Lenvatinib combined with radiotherapy, 8 patients received Lenvatinib alone. At a median treatment time of 8 months, the objective response rate (ORR) of the entire cohort was 58.2% (53 patients), including 7 patients with CR and 46 patients with PR. 21 patients (23.1%) had SD. The disease control rate (DCR) of all patients was 81.3% (74 patients). However, 17 patients (18.7%) developed PD. The 1- and 2-year cumulative OS rates for the entire cohort were 66.8% and 39.3%, while the corresponding PFS rates were 38.0% and 17.1%, respectively. Univariate and multivariate Cox regression analysis revealed multiple tumor sites to be an independent OS risk factor for uHCC patients (HR=2.204, 95% CI=1.104-4.399, P=0.025). The most frequently reported adverse events in all patients were AST elevation (51.6%), followed by hypertension (33.0%), ALT elevation (26.4%), and decreased appetite (25.3%). After a combination treatment of Lenvatinib-based therapies, 15 patients met the criteria for salvage liver resection and underwent down-staging hepatectomy with a curative intent. The combination of PD-1 treatment was not very effective in improving the prognosis of uHCC patients treated with Lenvatinib combined with TACE. Conclusion: Our study demonstrated that a proportive of patients benefited from Lenvatinib-based combination therapies with manageable safety profiles, allowing these patients to undergo downstaging surgery with curative intent.

Selective main portal vein clamping to minimize the risk of recurrence after curative liver resection for hepatocellular carcinoma.

BACKGROUND/AIMS: Our aim was to compare the postoperative outcomes of partial hepatectomy using Pringle maneuver and selective main portal vein clamping. METHODOLOGY: From January 2004 to December 2006, 169 consecutive patients received liver resection by the same surgical team. The surgical techniques were the same for all patients except for the hepatic vascular inflow occlusion techniques during liver parenchymal transection. Patients either received clamping of the portal triad (PTC group, n=118) or selective main portal vein clamping (PVC group, n=51). RESULTS: Operative time to carry out PVC was significantly longer than PTC (110.6±21.8 vs. 129.6±29.8min), however intraoperative blood loss was the same. There was no significant difference in operative mortality or morbidity rates, although the liver function recovered quicker in the PVC group. Significantly more patients in the PTC group developed HCC recurrence at postoperative one year than the PVC group (60.2% vs. 33.3%). There was no significant difference in overall survival between the 2 groups. Univariate analysis showed that clamping method, tumor size and BCLC grade were risk factors for disease-free survival (DFS) at one year, and multivariate analyses demonstrated clamping method and AFP level as independent risk factors for DFS. CONCLUSIONS: Patients subjected to selective portal vein clamping did better than those to Pringle maneuver in the postoperative outcomes. The underlying mechanism may be I/R injury of the liver remnant which might also contribute to an increase in tumor recurrence after liver resection.

[Hepatic vein occlusion with Satinsky clamp in hepatectomy for complicated liver tumor].

OBJECTIVE: To investigate the application of an improved method of hepatic vein occlusion with Satinsky clamp when resecting the liver tumor involving second hepatic portal. METHODS: From January 2003 to December 2010, there were totally 330 patients with liver tumor admitted, who underwent liver resection with Pringle maneuver plus hepatic vein occlusion with Satinsky clamp. Data regarding the intra-operative and post-operative course of the patients were analyzed. There were 245 male and 85 female patients, with a mean age of (50 ± 11) years. The diameter of tumor was (9 ± 6) cm. Among the 330 patients, there were 271 patients with viral hepatitis B, 215 patients with liver cirrhosis; 321 patients were in Child class A of liver function and 9 in class B. Pringle maneuver plus hepatic vein occlusion with Satinsky clamp was used to occlude the blood flow in the liver resection. The liver transection was performed with clamp-crushing technique. RESULTS: Hepatic vein occlusion with Satinsky clamp was successful in all 330 patients. The operation time was (132 ± 29) minutes, while (7 ± 3) minutes for dissecting hepatic vein and (22 ± 7) minutes for inflow blood occlusion. The blood loss in operation was (480 ± 265) ml, with 20% of patients receiving blood transfusion. No patient had large hemorrhage and air embolism due to hepatic vein laceration. No patient died in the perioperative period. The complications included 31 patients of pleural effusion, 14 patients of seroperitoneum, 10 patients of biliary fistula, 2 patients of massive blood loss during liver resection and 2 patients of re-bleeding after operation. CONCLUSION: The method of hepatic vein occlusion with Satinsky clamp was safe and effective.

Primary hepatic paraganglioma mimicking hepatocellular carcinoma: a case report.

Background: Primary hepatic paraganglioma (HPGL) originates from sympathetic nervous tissue in the liver. It is one of an exceedingly rare kind of sympathetic paragangliomas. The radiological features and clinical characters of HPGL can be easily confused with hepatocellular carcinoma (HCC). We present a case of HCC that was preoperatively diagnosed as hepatic paraganglioma, however, was pathologically verified as hepatic paraganglioma after surgery. Case Description: The present case reported a 47-year-old female with a very rare HPGL without any clinical symptoms, except for hyper menorrhagia and paroxysmal hypertension. The Spiegelman lobe of the liver underwent hepatic magnetic resonance imaging, which revealed a 3.2×3.8 cm mass, with uneven arterial phase wash-in and rapid portal and delayed phase wash-out. According to the imaging results, the patient was first diagnosed with hepatocellular carcinoma, and a radical hepatectomy was performed. However, the blood pressure of the patient displayed dramatic changes when the tumor was stimulated in operation. There were no substantial abnormalities found in the bilateral renal and adrenal glands. Therefore, we presumed that the tumor was related to functional pheochromocytoma. The tumor tissue was shown to be positive for chromogranin A, synaptophysin, CD56, and vimentin by immunohistochemical analysis. As a result, the patient was diagnosed with HPGL after this pathologic evaluation. Conclusions: There are several similarities between HPGL and HCC. For the treatment of hepatic paraganglioma, surgical excision is the recommended practice. Although the majority of paragangliomas are benign, long-term monitoring is required to differentiate benign from malignant paragangliomas.

Associating liver partition and portal vein ligation for staged hepatectomy versus sequential transarterial chemoembolization and portal vein embolization in staged hepatectomy for HBV-related hepatocellular carcinoma: a randomized comparative study.

Background: Both portal vein embolization (PVE) and associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) have merits and demerits when used in patients with unresectable liver cancers due to insufficient volumes in future liver remnant (FLR). Methods: This study was a single-center, prospective randomized comparative study. Patients with the diagnosis of hepatitis B related hepatocellular carcinoma (HCC) were randomly assigned in a 1:1 ratio to the 2 groups. The primary endpoints were tumor resection and three-year overall survival (OS) rates. Results: Between November 2014 to June 2016, 76 patients with unresectable HBV-related HCC due to inadequate volume of FLR were randomly assigned to ALPPS groups (n=38) and TACE + PVE groups (n=38). Thirty-seven patients (97.4%) in the ALPPS group compared with 25 patients (65.8%) in the TACE + PVE group were able to undergo staged hepatectomy (risk ratio 1.48, 95% CI: 1.17-1.87, P<0.001). The three-year OS rate of the ALPPS group (65.8%) (95% CI: 50.7-80.9) was significantly better than the TACE + PVE group (42.1%) (95% CI: 26.4-57.8) (HR 0.50, 95% CI: 0.26-0.98, two-sided P=0.036). However, no significant difference in the OS rates between patients who underwent tumor resection in the 2 groups of patients was found (HR 0.80, 95% CI: 0.35-1.83, two-sided P=0.595). Major postoperative complications rates after the stage-2 hepatectomy were 54.1% in the ALPPS group and 20.0% in the TACE + PVE group (risk ratio 2.70, 95% CI: 1.17-6.25, P=0.007). Conclusions: ALPPS resulted in significantly better intermediate-term OS outcomes, at the expenses of a significantly higher perioperative morbidity rate compared with TACE + PVE in patients who had initially unresectable HBV-related HCC.

One- versus two-stage partial hepatectomy for large resectable solitary hepatocellular carcinomas determined preoperatively to have a narrow resection margin: a propensity score matching analysis.

Background: For patients with a large but resectable solitary hepatocellular carcinoma (HCC) of >5 cm in diameter, it is often difficult to achieve a sufficient resection margin. There is still no study on whether a two-stage hepatectomy to increase a narrow resection margin would be beneficial. Methods: From August 2014 to February 2017, patients with a large but resectable solitary HCC of >5 cm and a preoperative estimated resection margin of <1.0 cm were retrospectively studied. They were divided into one- and two-stage resection groups. A retrospective analysis was performed, followed by propensity score matching (PSM) analysis. Disease recurrence, survival, intraoperative and postoperative data were compared. Results: Before PSM, the 1-, 2-, 3-and 4-year recurrence-free survival rates for the one- and two-stage groups were 44.3%, 31.7%, 24.3%, 19.2% versus 60.6%, 45.4%, 43.5%, 32.3%, respectively (P=0.007). The corresponding OS rates were 61.0%, 45.2%, 43.8%, 38.4% versus 69.6%, 62.5%, 60.7%, 57.3%, respectively (P=0.029). After PSM, the 1-, 2-, 3-and 4-year recurrence-free survival rates for the one- and two-stage groups were 44.0%, 31.5%, 27.3%, 21.0% versus 60.6%, 45.4%, 43.5%, 32.3%, respectively (P=0.013). The corresponding OS rates were 62.5%, 41.1%, 41.1%, 37.5% versus 69.6%, 62.5%, 60.7%, 57.3%, respectively (P=0.038). Differences in the resection margins between the one- and two-stage groups before [0.3 (0-0.5) versus 1.2 (0.8-2.2) cm] and after [0.2 (0-0.5) versus 1.2 (0.8-2.2) cm] PSM were also significant. Conclusions: Two-stage hepatectomy allowed a wider resection margin for patients with a resectable but solitary HCC of >5 cm, and resulted in significantly better long-term survival outcomes after partial hepatectomy.

Primary hepatic malignant fibrous histiocytoma: diagnostic pitfalls and therapeutic challenge.

BACKGROUND: Due to the rarity of primary hepatic malignant fibrous histiocytoma (MFH), the natural history, optimal management and prognosis are poorly characterized. METHODOLOGY: Between January 2003 and December 2008, we treated 12 consecutive patients with primary hepatic MFH. The patient demographics, tumor characteristics, type of treatment and actuarial survival were analyzed. RESULTS: The mean +/- SD tumor size was 8.4 +/- 3.2cm. Four patients had satellite lesions. R0, R1 and R2 resection of the liver tumor were achieved in 5, 2 and 5 patients, respectively. There was no hospital mortality and the complication rate was 8.3%. At a median follow-up of 11.3 months, local recurrence had occurred in 6 patients and local recurrence + distant metastases in 3 patients. Most patients (8/12) died of the tumor within a year after surgery, with a median survival of 6.1 months. For the remaining 4 patients, 2 patients had undergone surgery for less than 1 year previously, one patient who had a R0 liver resection with extrahepatic metastasis survived for 14 months with multiple metastases, and another patient who had a R0 liver resection but without extrahepatic metastasis survived for 60 months and was disease free. The median survival for the R0 liver resection group carried out in patients without extrahepatic metastases was 8.5 months, while the median survival of the debulking group (R0 liver resection with extrahepatic metastasis/ R1 or R2 liver resection) was 7 months. There was no significant difference in survival between the two groups. CONCLUSION: Hepatic resection was safe for patients with primary MFH with a poor prognosis. Complete resection offers the only hope of long-term disease free survival.

Prediction of Patient Survival Following Hepatic Resection in Early-Stage Hepatocellular Carcinoma with Indexed Ratios of Aspartate Aminotransferase to Platelets: A Retrospective Cohort Study.

PURPOSE: To predict patient survival in early-stage hepatocellular carcinoma (HCC) following hepatic resection. We evaluated the prognostic potential of the aspartate aminotransferase to platelet ratio index (APRI) in order to use it to model a nomogram. PATIENTS AND METHODS: We randomized 901 early-stage HCC patients treated with hepatic resection at our center into training and validation cohorts that were followed from January 2009 to December 2012. X-tile software was used to establish the APRI cut-off threshold in the training cohort. The validation cohort was subsequently assessed to determine threshold value accuracy. Data generated from the multivariate analysis in the training cohort were used to design a prognostic nomogram. Decision curve analyses (DCA), concordance index values (C-index) and calibration curves were used to determine the performance of the nomogram. RESULTS: X-tile software revealed that the optimal APRI cut-off threshold in the training cohort that distinguished between patients with different prognoses was 0.9. We, therefore, validated its prognostic value. Multivariate analyses showed that poor overall survival was associated with APRI above 0.9, blood loss of more than 400 mL, liver cirrhosis, multiple tumors, tumor size greater than 5 cm, microvascular invasion and satellite lesions. When the independent risk factors were integrated into the prognostic nomogram, it performed well with accurate predictions. Indeed, the performance was better than comparative prognosticators (P<0.05 for all) with 0.752 as the C-index (95% CI: 0.706-0.798). These results were verified by the validation cohort. CONCLUSION: APRI was a noninvasive and accurate predictive indicator for patients with early-stage HCC. Following hepatic resection to treat early-stage HCC, individualized patient survival predictions can be aided by the nomogram based on APRI.

Inflammatory myofibroblastic tumor of the liver: a cohort study.

BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is a rare condition. The aim of the present study was to evaluate the clinical characteristics and surgical outcomes for IMT of the liver in our large cohort of patients. METHODS: From January 2001 to December 2007, all patients with a pathological diagnosis of IMT of the liver who underwent partial hepatectomy were retrospectively analyzed. RESULTS: During the study period, 64 patients underwent partial hepatectomy for IMT of the liver in our tertiary referral center. The commonest clinical presentation was abdominal pain (53%), followed by fever (41%); 15.6% of patients were asymptomatic. Preoperative diagnosis of IMT was suspected in only five patients (8%). The indications for surgery included suspicion of malignancy (60.9%), uncertain diagnosis (40.6%), symptomatic disease (26.6%), and spontaneous rupture (3.1%). The postoperative complication rate was low (17.2%). There was no hospital mortality. After a median follow-up of 30 months, no patient developed recurrence. CONCLUSIONS: Although there are various treatment options for IMT of the liver, surgical resection for good risk patients is preferred.

Nomograms to predict the long-time prognosis in patients with alpha-fetoprotein negative hepatocellular carcinoma following radical resection.

BACKGROUND: To develop and validate nomograms that can be used to predict outcomes in individuals suffering alpha-fetoprotein (AFP) negative hepatocellular carcinoma (HCC) after radical resection. METHODS: A total of 509 AFP-negative HCC patients who received hepatectomy between January 2009 and March 2013 in our center were randomized into training and validation cohorts. Nomograms for both overall and recurrence-free survival (OS and RFS, respectively) were established based on the predictors in the training cohort. Nomograms performance and discriminative power were assessed with concordance index (C-index) values and decision curve analyses (DCA). The results were validated in the validation cohort. RESULTS: Alkaline phosphatase, liver cirrhosis, tumor size, satellite lesions, microvascular invasion, and Edmondson-Steiner grade were significantly linked to OS and RFS. Sex and tumor number were additional predictors for RFS. The OS nomogram had a C-index value of 0.742, which was better than that for the AJCC eighth edition (0.632), BCLC system (0.553), and JIS score (0.557) (all P < .001). The RFS nomogram C-index was 0.669, which was also superior to that of the AJCC eighth (0.608), BCLC stage (0.554), JIS score (0.551), and model of Gan et al (0.636) (P < .05 for all). Calibration curves indicated a good agreement between observed actual outcomes and predicted values. Kaplan-Meier curves and DCA indicated that nomograms were powerful in discrimination and clinical usefulness. These results were supported by the validation cohort. CONCLUSIONS: These nomograms presented more accurate prognostic prediction in patients with AFP-negative HCC after hepatectomy.