Abstract:Hepatic resection is the standard treatment for early-stage hepatocellular carcinoma (HCC). However, its application in HCC patients at middle- and advanced-stage or with portal hypertension is controversial because of the high incidence of perioperative complications and mortality rates, and low long-term disease-free and overall survival rates. Here, the authors discuss the issues of these concerns.

Abstract:Objective: To determine the efficacy of anatomic segmental hepatic resection under real-time ultrasound navigation in treatment of hepatocellular carcinoma (HCC). Methods: The clinical data of 30 HCC patients undergoing anatomic segmental hepatic resection under real-time ultrasound navigation (observation group) and 30 HCC patients who were subjected to non-anatomic liver resection (control group) from June 2014 to June 2015 in Anhui Provincial Hospital of Anhui Medical University were reviewed. The main clinical variables between the two groups of patients were compared. Results: The preoperative data between the two groups of patients were comparable. In observation group versus control group, the operative time was prolonged (153.5 min vs. 128.5 min, P<0.05), and the intraoperative blood loss showed no significant difference (175.0 mL vs. 200.00 mL, P>0.05), but the intraoperative blood transfusion rate (10.0% vs. 36.7%, P<0.05) and hepatic portal occlusion rate (16.7% vs. 40.0%, P<0.05) were significantly reduced. There was no significant difference in incidence of postoperative complications between the two groups (13.3% vs. 33.3%, P>0.05). In observation group, the 1-year recurrence rate was significantly lower than that in control group (16.7% vs. 43.3%, P<0.05), while 1-year survival rate was significantly higher than that in control group (80.0% vs. 53.3%, P<0.05). Conclusion: Application of anatomic segmental hepatic resection under real-time ultrasound navigation has a beneficial effect on reducing postoperative recurrence and improving prognosis in HCC patients.

Abstract:Objective: To investigate the clinical application value of three-dimensional (3D) laparoscopic liver resection for primary liver cancer. Methods: Using prospective non-randomized controlled design, 90 patients with primary liver cancer admitted from March 2012 to October 2015 were enrolled and underwent 3D high-definition laparoscopic liver resection (3D group, 48 cases) and traditional two-dimensional (2D) laparoscopic liver resection (2D group, 42 cases) respectively. The main clinical variables between the two groups of patients were compared. Results: The preoperative data were comparable between the two groups of patients. The surgical procedure, intraoperative blood loss, volume of transfusions, incidence of postoperative complications, length of hospital stay and hospitalization costs showed no statistical difference between the two groups (all P>0.05), but the operative time in 3D group was significantly less than that in 2D group (522 min vs. 566 min, P=0.001). Conclusion: 3D high-definition laparoscopic liver resection is helpful in precise dissection and shortening operative time, without increasing associated injuries and total hospitalization costs. So it is a safe, effective, economical and minimally invasive procedure.

Abstract:Objective: To compare the efficacy of ultrasound guided percutaneous radiofrequency ablation (RFA) and laparoscopic hepatectomy in treatment of small primary cancer of the liver (diameter≤3 cm). Methods: The clinical data of 35 patients with small primary liver cancer undergoing ultrasound guided RFA (ablation group) from January 2012 to June 2015, and 30 patients undergoing laparoscopic hepatectomy (laparoscopic group) during the same period were retrospectively analyzed. The relevant surgical variables as well as the postoperative recurrence and survival rates between the two groups were compared. Results: In ablation group compared with laparoscopic group, the operative time (53.89 min vs. 128.57 min), intraoperative blood loss (7.29 mL vs. 115.33 mL), length of postoperative hospital stay (1.86 d vs. 5.50 d) and hospitalization cost (17 300 yuan vs. 22 300 yuan) were all significantly reduced (all P<0.05), while the changes in liver function parameters and incidence of postoperative complications had no statistical difference (all P>0.05). There was no significant difference in radical surgery rates (97.1% vs. 100.0%) and 3-year recurrence rates (51.4% vs. 40.0%) as well as 1-, 2- and 3-year disease-free survival rates (74.3% vs. 76.7%, 62.9% vs. 66.7%, 37.1% vs. 40.0%) and overall survival rates between ablation group and laparoscopic group (85.7% vs. 86.7%, 82.9% vs. 83.3%, 77.1% vs. 80.0%). Conclusion: RFA and laparoscopic hepatectomy have similar efficacy for small primary liver cancer. Therefore, RFA has the advantages of minimal invasiveness, shorter operative time and fast postperative recovery, so it has important clinical therapeutic value for small primary liver cancer.

Abstract:Objective: To investigate the clinical efficacy of emergency hepatectomy in treatment of spontaneous rupture and hemorrhage of hepatocellular carcinoma (HCC). Methods: The clinical data of 57 patients with rupture and hemorrhage of HCC undergoing emergency hepatectomy from January 2005 to December 2014 were retrospectively analyzed. Results: All patients underwent successful emergency hepatectomy, and the in-hospital mortality was 10.5%. The 1-, 3- and 5-year overall survival rate was 77.6%, 51.0% and 32.7% and disease-free survival rate was 69.4%, 40.8% and 18.4%, respectively, with the median survival time of 38.7 months. Of the 49 patients receiving follow-up, recurrence occurred in 38 cases, including intrahepatic recurrence in 18 cases (47.4%), and extrahepatic metastasis in 20 cases (52.6%). The multivariate analysis showed that tumor size larger than 10 cm (HR=2.43, P=0.031) and multiple lesions (HR=0.46, P=0.028) were independent factors affecting the postoperative survival of the patients. Conclusion: After appropriate selection, emergency hepatectomy for resectable HCC with rupture and hemorrhage is a life-saving and long-term effective treatment.

Abstract:Objective: To investigate the application value of high frequency electric knife in liver resection for hepatocellular carcinoma (HCC). Methods: A total of 386 HCC patients were divided into observation group (n=199) and control group (n=187). Liver resection was performed by electric coagulation knife with an output power of 120 W in patients in observation group, and was performed by ultrasonic knife through clamp crushing method in control group. The clinical variables that included time of hepatic inflow occlusion, operative time, intraoperative blood loss, intra- and post-operative transfusion of red blood cells (RBC), postoperative drainage, changes in liver function, postoperative complications, and length of hospital stay were compared between the two groups. Results: Operation was successfully performed in all patients, and no burn injuries or electrocardiographic abnormalities caused by high-power and high-frequency current were noted in observation group. In observation group compared with control group, the operative time (192.79 min vs. 212.10 min), hepatic inflow occlusion time (5.17 min vs. 14.65 min), incidence of postoperative complications (21.1% vs. 34.2%), ratio of postoperative RBC transfusion (25.7% vs. 36.7%) and length of postoperative hospital stay (8.87 d vs. 12.15 d) were all significantly reduced (all P<0.05), but the intraoperative blood loss (378.56 mL vs. 412.75 mL), ratio of intraoperative RBC transfusion (7.5% vs. 7.5%), and time to postoperative tube removal (5.83 d vs. 6.29 d) showed no significant difference (all P>0.05). Some liver function parameters on postoperative day 1 and 3 in observation group were superior to those in control group (all P<0.05). There was no significant difference in postoperative 1-, 2- and 3-year overall survival rates between the two groups (all P>0.05). Conclusion: Using high-frequency electric knife in liver resection for HCC has fast speed of resection and good hemostatic effect, and its use is safe and reliable.

Abstract:Objective: To investigate the expression of BTB/POZ domain-containing protein 7 (BTBD7) pseudogene 1 (BTBD7P1) in hepatocellular carcinoma (HCC) and its action. Methods: The BTBD7P1 mRNA expressions in 106 paired specimens of HCC tissue and its adjacent tissue were determined, and the relations of BTBD7P1 mRNA expression with the clinicopathologic features and prognosis of the HCC patients were analyzed. In HCC Bel7404 cells after transfected with BTBD7P1 overexpression lentiviral vectors, the proliferation and expressions of BTBD7 mRNA and protein were measured. Results: The relative expression level of BTBD7P1 mRNA in HCC tissue was significantly lower than that in adjacent tissue (0.71 vs. 2.14, P<0.05); lower expression of BTBD7P1 was significantly associated with tumor size, satellite lesions, degree of differentiation, vascular invasion, hemorrhagic necrosis, and stage of HCC (all P<0.05); the 1-, 3- and 5-year overall and tumor-free survival rates in patients with low BTBD7P1 mRNA expression were significantly lower than those in patients with higher BTBD7P1 mRNA expression (both P<0.05). In Bel7404 cells transfected with BTBD7P1 overexpression lentiviral vectors, the cell proliferation was significantly decreased and the BTBD7 mRNA expression was significantly down-regulated (both P<0.05), but BTBD7 protein expression showed no significant change (P>0.05) compared with control Bel7404 cells transfected with empty vectors. Conclusion: BTBD7P1 may probably regulate the expression of its parental gene BTBD7 at mRNA level and thereby participate in the occurrence and development of HCC.

Abstract:Objective: To investigate the impact of RGD peptide (TyrRGD) modified gold nanoparticles (GNPs) conjugated to VEGF siRNA (TyrRGD-GNPs-VEGFsiRNA) on damaging effect of radiofrequency ablation (RFA) for rabbit VX2 tumor. Methods: Rabbit models of VX2 liver were established by direct implantation of VX2 tumor fragment into the liver via laparotomy. Firstly, 6 liver tumor-bearing rabbits were equally divided into 2 groups and underwent injection of TyrRGD-GNPs-VEGFsiRNA or naked GNPs respectively, and the collection and distribution of the two substances in the tumor samples were detected by transmission electron microscopy 48 h after injection. Next, 30 liver tumor-bearing rabbits were equally divided into 3 groups and underwent RFA treatment 48 h after injection of TyrRGD-GNPs-VEGFsiRNA, naked GNPs or normal saline, respectively, and the tumor specimens were harvested 48 h later, after which, pathological observation was performed, the ablation volume of the tumor was measured and the apoptosis in the residual cancer was detected by TUNEL staining. Finally, 27 liver tumor-bearing rabbits were equally divided into 3 groups and underwent treatment of RFA plus TyrRGD-GNPs-VEGFsiRNA injection, RFA plus normal saline injection or normal saline injection only, and then were fed until they naturally died and the survival times were recorded. Results: The accumulation of TyrRGD-GNPs-VEGFsiRNA in the tumor was significantly greater than that of naked GNPs (14.2/500-nm field vs. 0/500-nm field, P<0.01). The ablation volume by RFA after injection of TyrRGD-GNPs-VEGFsiRNA was significantly larger than that after injection of either naked GNPs or normal saline (5.12 cm3 vs. 1.78 cm3 vs. 1.49 cm3, P<0.01), moreover, the cell number of apoptosis in the residual cancer in the former was significantly higher than those in the two latter groups (111.7 vs. 36.3 vs. 34.7, P<0.01), but both above two parameters showed no statistical difference between the two latter groups (both P>0.05). The mean survival time for liver tumor-bearing rabbits undergoing RFA plus TyrRGD-GNPs-VEGFsiRNA injection was significantly prolonged compared with those undergoing RFA plus saline injection or normal saline injection only (70.9 d vs. 51.2 d vs. 43.9 d, P<0.01). Conclusion: TyrRGD-GNPs-VEGFsiRNA can targetedly aggregate in liver tumor, and it also has the effect of expanding the extent of RFA damage and promoting the apoptosis of the tumor cells, and thereby enhance the efficacy of RFA treatment.

Abstract:Objective: To create the animal model of associating liver partition and portal vein ligation (PVL) for staged hepatectomy (ALPPS) in rats. Methods: Sixty healthy male SD rats were equally randomized into PVL group, ALPPS group and sham group. Rats in PVL group underwent ligation of the portal vein branches for the left lateral, left middle, and right lobes of the liver and complete caudate lobe resection, with preservation of the branches for the right middle lobe; rats in ALPPS group underwent the same procedures as those of PVL group combined with parenchyma splitting of the middle lobe of the liver along the ischemic boundary; rats in sham group underwent dissociation of the portal veins without ligation. The postoperative hepatic regeneration rate (HRR) and liver function were determined, and the pathological changes in the left middle lobe of the liver and Ki-67 expression in the right middle lobe of the liver were examined. Results: Compared with sham group, the HRR of the right middle lobe in both ALPPS group and PVL group were significantly higher than that in sham group at any postoperative time point (all P<0.05), and the HRR of the right middle lobe in ALPPS group was significantly higher than that in PVL group on postoperative day (POD) 4 and 7 (155.96% vs. 118.15%; 174.86% vs. 133.55%, both P<0.05). The liver function parameters in PVL group were better than those in ALPPS group at early postoperative stage (all P<0.05), but showed no significant difference in late postoperative stage between the two groups (all P>0.05). Results of histopathological examinations showed that the focal necrosis in the left middle lobe of the liver was more intense in ALPPS group than that in PVL group on POD 1 (P<0.05), and the Ki-67 positive index in the tissue of the right middle lobe in ALPPS group was significantly higher than that in PVL group on POD 2 and 4 (85.36% vs. 61.84%; 43.40% vs. 29.06%, both P<0.05). Conclusion: Both ALPPS and PVL can promote hepatic regeneration, but ALPPS is faster than PVL in promoting hepatic regeneration. A rat model of ALPPS has been successfully established, which may provide a basis for further investigation on the mechanism of ALPPS induced liver regeneration and ALPPS-associated complications.

Abstract:Objective: To investigate the expression of FK506 binding protein 5 (FKBP5) in hepatocellular carcinoma (HCC) and its clinical significance. Methods: The expressions of FKBP5 mRNA and protein in 30 fresh HCC and the adjacent tissue paired samples were determined by RT-PCR and Western blot, respectively. Then, immunohistochemical staining was performed in paraffin-embedded specimens from 107 HCC patients and the relations of FKBP5 expression with clinicopathologic features and prognosis of HCC patients were analyzed. Results: Of the 30 fresh HCC tissues, 26 samples (86.7%) showed that the FKBP5 mRNA expression level was markedly higher in HCC tissue than that in its adjacent tissue, and FKBP5 protein expression level in HCC tissue was also markedly increased compared with adjacent normal tissue. In the 107 paraffin-embedded specimens, the high expression rate of FKBP5 protein in HCC tissues was significantly higher than that in adjacent tissues (63.6% vs. 28.0%, P<0.001); high FKBP5 expression was significantly associated with tumor size (P=0.009), lesion number (P=0.018), microvascular invasion (P=0.020), TNM stage (P=0.009) and BCLC stage (P=0.024); both overall survival rate and disease-free survival rate in patients with high FKBP5 expression were significantly lower than those in patients with low FKBP5 expression (both P<0.001); high FKBP5 expression was an independent risk factor for either overall survival (HR=1.992, 95% CI=1.127–3.522, P=0.018) or disease-free survival (HR=1.787, 95% CI=1.067–2.992, P=0.027). Conclusion: FKBP5 expression is increased in HCC tissue, and its overexpression is associated with unfavorable clinicopathologic features and poor prognosis of HCC patients, suggesting that FKBP5 may be a potential prognostic indicator for HCC.

Abstract:Objective: To analyze the difference in circular RNA (circRNA) expression profiles between hepatocellular carcinoma (HCC) tissue and normal liver tissue. Methods: The circRNA expression profiles in 3 paired specimens of HCC tissue and its adjacent liver tissue were detected by using the human circRNA microarray. After preprocessing and homogenization of the original data, the differentially expressed circRNAs were searched out (the circRNA in HCC tissue showed a greater than 1.5-fold change which was also statistically significant compared with adjacent liver tissue and was regarded as differentially expressed circRNA). Then, after these circRNAs screening according to the principle of higher fold change and better consistency and their putatively targeting miRNAs prediction by bioinformatics software combined with literature review, the circRNAs that potentially contribute to HCC development were preliminarily identified. Results: The circRNA expression profile in HCC showed remarkable changes compared with adjacent hepatic tissue. In HCC tissue, a total of 82 circRNAs showed a greater than 1.5-fold change, and of them, 21 were up-regulated and 61 were down-regulated; a total of 3 circRNAs showed a greater than 5-fold change, and of them, 2 were up-regulated and 1 was down-regulated. The significantly up-regulated circRNA hsa-circ-0043278 (8.15 fold, P=0.002) and hsa-circ-0006220 (12.73 fold, P=0.033), and significantly down-regulated circRNA hsa-circ-0065214 (6.28 fold, P=0.019) were finally obtained after screening. Bioinformatics analysis and literature review suggested that hsa-miR-520 was potentially regulated by hsa-circ-0043278 and hsa-circ-0006220, which contributed to the occurrence and development of HCC. Conclusion: The circRNA expression profile in HCC is greatly changed. Hsa-circ-0043278 and hsa-circ-0006220 may play important roles in the occurrence and development of HCC.

Abstract:Objective: To introduce a novel method for liver parenchymal transaction, i.e., the snip-electrocoagulation technique. Methods: The clinical data of 30 consecutive patients undergoing liver resection for liver tumor in the Department of General Surgery of Xiangya Hospital, Central South University from June 2015 to February 2016 were reviewed. All patients received snip-electrocoagulation technique, namely using dissecting scissors and bipolar coagulation scalpel only, for parenchymal transection during operation. The perioperative data and the technical essentials of this method were analyzed. Results: Of the 30 patients, there were 24 cases of hepatocellular carcinoma with cirrhosis; the procedures included one segment resection in 10 cases, two segments resection in 12 cases and hemihepatectomy in 8 cases. The mean transection time, operative time, total blood loss and length of hospital stay was 19.8 (12–38) min, 129.3 (80–180) min, 207.5 (60–600) mL and 7.1 (5–14) d, respectively, and none of the patients required blood transfusion. Among 4 patients (13.3%), a total of 6 postoperative complications occurred, including pleural effusion and ascites in 4 cases, and pneumonia and bile leak in one case each, but all of them were managed successfully by conservative treatment. There was no rebleeding or death within postoperative one month. Conclusion: Snip-electrocoagulation technique is safe and effective for parenchymal transection, and it is recommended as an alternative method for parenchymal transection to be used in clinical practice.

Abstract:Objective: To investigate the clinical efficacy of stylized laparoscopic left lateral hepatic lobectomy in treatment of lesions in left lateral lobe of the liver. Methods: The clinical data of 139 patients with lesions in left lateral hepatic lobe (liver cancer, hemangioma, focal nodular hyperplasia, and intrahepatic stones) undergoing laparoscopic left lateral hepatic lobectomy from January 2009 to June 2016 in the Second Affiliated Hospital of Nanchang University were retrospectively analyzed. Of the patients, laparoscopic left lateral hepatic lobectomy in 63 cases was performed with a series of sequential and reliable procedure steps, with no requirements for meticulous dissection of the intrahepatic ducts (stylized group) and in 76 cases was performed with traditional procedures (traditional group). The main clinical variables between the two groups of patients were compared. Results: Laparoscopic left lateral hepatic lobectomy was completed in all patients in stylized group, while 5 cases in traditional group were converted to open surgery due to massive hemorrhage. In stylized group compared with traditional group, the operative time (80.4 min vs. 126.6 min), intraoperative blood loss (70.6 mL vs. 150.8 mL) and length of postoperative hospital stay (7.1 d vs. 10.4 d) were all significantly reduced (all P<0.05), while, the total hospitalization expense (35 600 yuan vs. 36 500 yuan), incidence of postoperative complications (7.9% vs. 14.5%) and postoperative 1-year recurrence rates of the liver cancer patients (11.1% vs. 14.7%) showed no statistical difference (P>0.05). Conclusion: Stylized laparoscopic left lateral hepatic lobectomy has demonstrable efficacy and the advantages of short operative time, less intraoperative blood loss and short length of hospital stay, moreover, it is simple and practicable. Thus, it is recommended to be generalized and broadly used.

Abstract:Objective: To investigate the clinical features, imaging manifestations and differential diagnosis of hepatocellular adenoma (HCA), for its accurate diagnosis and effective treatment. Methods: The clinical data of one HCA patient admitted recently was analyzed retrospectively, and the relevant literature was reviewed. Results: The preoperative imaging examinations of the patient showed a space-occupying lesion in the right lobe of the liver, and all tumor markers were negative but the serum γ-glutamyltransferase level was increased. The patient underwent segment V and partial segment VIII liver resection, and was pathologically diagnosed as HCA of the right hepatic lobe. Postoperative follow-up was conducted for two months, the patient had an uneventful recovery and no abnormality was noted in laboratory parameters or abdominal CT scan during follow-up visits. Conclusion: HCA is a rare benign liver tumor lacking specific clinical signs. Preoperative CT and contrast-enhanced MRI may improve the diagnostic rates of this disease. Surgical resection is the main treatment method for HCA in consideration of its hemorrhagic tendency and the possibility of malignant transformation, and offers favorable results.

Abstract:With the vigorous development of 3D printing technology in medical field, the traditional medicine is now under transition towards digital precision medicine. Precision liver surgery is characterized by offering the utmost recovery for the patients through accurate preoperative assessments and surgical planning as well as meticulous intraoperative dissection and hemostasis. The 3D technology can construct a simulation model of liver through imaging data which allows surgeons to have a full knowledge of the liver from a three-dimensional perspective, and thereby to make a perfect preoperative evaluation and planning. As an emerging discipline in recent years, 3D bioprinting is expected to resolve the problems such as shortage of liver transplant donor and deficiency of residual liver volume after liver resection in the future.

Abstract:In recent years, laparoscopic hepatectomy has increasingly become more established as a treatment option for various liver diseases, thanks to the rapid development in laparoscopic and minimally invasive techniques. However, it remains a challenging procedure because of difficulty in control of bleeding at the resection surface. The effective prevention and control of intraoperative bleeding is the basic premise for the completion of successful laparoscopic hepatectomy. At present, there are a variety of methods that have been used for prevention and control of intraoperative bleeding, including hepatic vascular occlusion, application of various devices for liver parenchymal transection, laparoscopic ultrasonography, controlled low central venous pressure, and resection surface treatments. Here, the authors review the current applications of these methods.

Abstract:In recent years, JAK2-STAT3 signaling pathway has been found to be involved in the growth, proliferation, differentiation, metastasis and apoptosis of tumor cells. JAK and STAT proteins are overexpressed in hepatocellular carcinoma (HCC) cells, and JAK2-STAT3 signaling pathway is closely related to the occurrence and development of HCC. In this article, the authors overview the research progress of JAK2-STAT3 signaling pathway in HCC.

Abstract:Most patients with hepatocellular carcinoma (HCC) lose the opportunity for radical treatment due to the insidious onset of HCC, thus chemotherapy plays an important role in treatment of HCC at middle and advanced stage. The etiology for and the molecular pathways involved in HCC have been further understood with the development of genetic knowledge and molecular biology, which provide the biological rationale for targeted therapy. In more than 10 recent years, some advances have been achieved in targeted drugs for HCC, and sorafenib has already been approved by FDA for advanced HCC, while the results of other clinical trials of targeted drugs are less than satisfactory, and the research of targeted drugs for HCC seems to enter a stagnant state. Here, the authors discuss the current advances in targeted therapy for HCC and analyze the causes for the failure of many clinical trials as well as the potential solutions.