Exosomal lncRNA HEIH, an essential communicator for hepatocellular carcinoma cells and macrophage M2 polarization through the miR-98-5p/STAT3 axis.

Part of human long noncoding RNAs (lncRNAs) has been elucidated to play an essential role in the carcinogenesis and progression of hepatocellular carcinoma (HCC), a type of malignant tumor with poor outcomes. Tumor-derived exosomes harboring lncRNAs have also been implicated as crucial mediators to orchestrate biological functions among neighbor tumor cells. The recruitment of tumor-associated macrophages (TAMs) exerting M2-like phenotype usually indicates the poor prognosis. Yet, the precise involvement of tumor-derived lncRNAs in cross-talk with environmental macrophages has not been fully identified. In this study, we reported the aberrantly overexpressed HCC upregulated EZH2-associated lncRNA (HEIH) in tumor tissues and cell lines was positively correlated with poor prognosis, as well as enriched exosomal HEIH levels in blood plasma and cell supernatants. Besides, HCC cell-derived exosomes transported HEIH into macrophages for triggering macrophage M2 polarization, thereby in turn promoting the proliferation, migration, and invasion of HCC cells. Mechanistically, HEIH acted as a miRNA sponge for miR-98-5p to up-regulate STAT3, which was then further verified in the tumor xenograft models. Collectively, our study provides the evidence for recognizing tumor-derived exosomal lncRNA HEIH as a novel regulatory function through targeting miR-98-5p/STAT3 axis in environmental macrophages, which may shed light on the complicated tumor microenvironment among tumor and immune cells for HCC treatment.

The safety and efficacy of TACE combined with HAIC, PD-1 inhibitors, and tyrosine kinase inhibitors for unresectable hepatocellular carcinoma: a retrospective study.

Objective: To assess the effectiveness and safety of transarterial chemoembolization (TACE) in combination with hepatic artery infusion chemotherapy (HAIC)、PD-1 inhibitors, and tyrosine kinase inhibitors(TKI) for unresectable hepatocellular carcinoma (HCC). Methods: A retrospective analysis was performed on 158 unresectable HCC patients admitted to the First Affiliated Hospital of Nanchang University between May 2019 and October 2022. The patients were split into two groups based on the type of treatment they received: TACE combined with HAIC,PD-1 and TKI group (THPK) and TACE combined with PD-1 and TKI group (TPK). The response was evaluated using modified solid tumor Efficacy Assessment Criteria (mRECIST). Kaplan-Meier curves were used to analyze the overall survival (OS). OS-influencing factors were identified using the Cox proportional risk regression model. Results: Finally, 63 patients who received THPK treatment and 60 patients who had TPK treatment were included. The THPK group had higher DCR (77.78% vs. 55.00%, P=0.007) and ORR (20.63% vs. 13.34%, P=0.282) than the TPK group did. The survival analysis curve also showed that the median OS was substantially longer in the THPK group than in the TPK group (OS: 21 months vs. 14 months, P=0.039). After multivariate Cox regression-corrected analysis, extrahepatic metastases (P=0.002) and methemoglobin >400 (P=0.041) were adverse influences on OS, but the THPK group (relative to the TPK group) was an independent favorable prognostic factor for OS (P=0.027). The results of the subgroup analysis showed that the addition of HAIC therapy to TPK treatment in patients with BCLC stage C, age ≦60 years, ECOG grade 0 and lobular distribution of tumors prolonged overall survival time and improved prognosis. Except for nausea, there was no difference in the adverse events between the two groups. Conclusion: In patients with unresectable HCC, the THPK group had a longer OS and similar adverse events compared to the TPK group. In the future, TACE-HAIC in combination with targeted and immunotherapy may be a more effective therapeutic option for hepatocellular carcinoma that cannot be surgically removed.

A hsa_circ_001726 axis regulated by E2F6 contributes to metastasis of hepatocellular carcinoma.

BACKGROUND: CircRNAs participate in the development of hepatocellular carcinoma (HCC). This work aims to explore the key tumor promoting circRNA as a gene therapy target. METHODS: The differentially expressed gene circRNAs in HCC tumor tissues was identified by mining GSE121714 dataset. EdU staining, wound healing, transwell invasion assay, TUNEL staining and western blotting examined proliferation, migration, invasion, apoptosis and epithelial mesenchymal transition (EMT). Xenograft mouse model and orthotopic transplantation tumor mouse model were constructed to verify the role of hsa_circ_001726 in growth and metastasis of HCC. The relationship among CCT2, E2F6, hsa_circ_001726, miR-671-5p and PRMT9 was identified by RNA-fluorescence in situ hybridization, luciferase reporter assay and RNA Immunoprecipitation. RESULTS: Eleven differentially expressed circRNAs were found in HCC tumors. Among them, hsa_circ_001726 was highly expressed in HCC tumors and cells, which was transcribed from CCT2. As a transcription factor of CCT2, E2F6 knockdown inactivated CCT2 promoter and reduced hsa_circ_001726 expression. Moreover, hsa_circ_001726 elevated PRMT9 expression by sponging miR-671-5p, and then activated Notch signaling pathway. Additionally, hsa_circ_001726 deficiency repressed malignant phenotypes of HCC cells, including proliferation, migration, invasion, EMT and apoptosis. In vivo, hsa_circ_001726 deficiency reduced tumor growth and lung metastasis of HCC in xenograft mouse models and orthotopic transplantation tumor mouse models. CONCLUSION: Hsa_circ_001726 functioned as an oncogene in HCC, which was derived from CCT2 and regulated by E2F6. Hsa_circ_001726 elevated PRMT9 expression by sponging miR-671-5p, and then activated Notch signaling pathway, thereby accelerating malignant phenotypes of HCC. Therefore, targeting hsa_circ_001726 may be a new avenue for HCC treatment.

Arginine methylation of HSPA8 by PRMT9 inhibits ferroptosis to accelerate hepatitis B virus-associated hepatocellular carcinoma progression.

BACKGROUND: The hepatitis B virus X (HBx) protein is an established cause of hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC). Whether arginine methylation regulates ferroptosis involved in HBx-induced HCC progression has not been reported. This study aimed to explore whether HBx-regulated protein arginine methyltransferase 9 (PRMT9) mediates the involvement of ferroptosis in the development of HCC. METHODS AND RESULTS: HBx inhibited ferroptosis through promoting PRMT9 expression in HCC cells. PRMT9 suppressed ferroptosis to accelerate HCC progression in vivo. PRMT9 targeted HSPA8 and enhanced arginine methylation of HSPA8 at R76 and R100 to regulate ferroptosis in HCC. HSPA8 overexpression altered the transcriptome profile of HepG2 cells, in particular, ferroptosis and immune-related pathways were significantly enriched by differentially expressed genes, including CD44. HSPA8 overexpression up-regulated CD44 expression and knockdown of CD44 significantly reversed the inhibition of ferroptosis caused by PRMT9 overexpression. CONCLUSIONS: In conclusion, HBx/PRMT9/HSPA8/CD44 axis is a vital signal pathway regulating ferroptosis in HCC cells. This study provides new opportunities and targets for the treatment of HBV-induced HCC.

Male urogenital function after robot-assisted and laparoscopic total mesorectal excision for rectal cancer: a prospective cohort study.

BACKGROUND: Urogenital dysfunction is recognized as a serious complication affecting patient quality of life after rectal cancer surgery to treat rectal cancer; however, the studies focus on the urogenital function after robot-assisted rectal cancer surgery compared to laparoscopic surgery are limited. METHODS: Male patients undergoing robotic total mesorectal excision (R-TME) or laparoscopic total mesorectal excision (L-TME) were prospectively enrolled. The International Prostate Symptom Score (IPSS) and the five-item version of the International Index of Erectile Function (IIEF-5) scale were used to compare the urogenital function of the two groups preoperatively and 3, 6, and 12 months postoperatively. RESULTS: Eighty-nine patients who planned to undergo R-TME and L-TME were prospectively enrolled; 77 patients of these patients (86.5%) completed all questionnaires at all time points and were thus included in the final analysis. Of the included patients, 38 underwent R-TME and 39 underwent L-TME. There was no significant difference in age, BMI, American Society of Anesthesiologists (ASA) score, tumor location, neoadjuvant therapy, operation method, postoperative pathological results and adjuvant therapy between the two groups. Preoperative urogenital function was similar in both groups; however, the IPSS was significantly lower in R-TME patients than that in T-TME patients at 6 months and 12 months [(7.82 ± 2.25 vs. 9.95 ± 3.01, P = 0.006; 7.62 ± 2.5 vs. 9.12 ± 2.64, P = 0.012)]. IIEF-5 scores decreased 3 months after R-TME and L-TME surgery (14.87 ± 3.27 vs. 13.92 ± 3.62, p = 0.231) and then gradually increased; at 12 months, IIEF-5 scores were comparable to those at baseline in both groups. IIEF-5 scores were higher in R-TME patients than those in L-TME patients at 6 months (18.55 ± 3.45 vs. 16.75 ± 3.26, P = 0.021), but there was no significant difference between the two groups at 12 months (21.22 ± 3.06 vs. 19.95 ± 3.03, P = 0.071). CONCLUSIONS: The robotic approach for TME was associated with more rapid restoration of male urogenital function than the laparoscopic approach.

Therapeutic implications of exosomes in the treatment of radiation injury.

Radiotherapy is one of the main cancer treatments, but it may damage normal tissue and cause various side effects. At present, radioprotective agents used in clinics have side effects such as nausea, vomiting, diarrhea and hypotension, which limit their clinical application. It has been found that exosomes play an indispensable role in radiation injury. Exosomes are lipid bilayer vesicles that carry various bioactive substances, such as proteins, lipids and microRNA (miRNA), that play a key role in cell-to-cell communication and affect tissue injury and repair. In addition, studies have shown that radiation can increase the uptake of exosomes in cells and affect the composition and secretion of exosomes. Here, we review the existing studies and discuss the effects of radiation on exosomes and the role of exosomes in radiation injury, aiming to provide new insights for the treatment of radiation injury.

Comparison of robotic and laparoscopic rectal cancer surgery: a meta-analysis of randomized controlled trials.

OBJECTIVE: Robotic and laparoscopic surgery for rectal cancer has been applied in the clinic for decades; nevertheless, which surgical approach has a lower rate of postoperative complications is still inconclusive. Therefore, the aim of this meta-analysis was to compare the postoperative complications within 30 days between robotic and laparoscopic rectal cancer surgery based on randomized controlled trials. METHODS: Randomized controlled trials (until May 2020) that compared robotic and laparoscopic rectal cancer surgery were searched through PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, and China Biology Medicine disc (CBMdisc). Data regarding sample size, clinical and demographic characteristics, and postoperative complications within 30 days, including overall postoperative complications, severe postoperative complications (Clavien-Dindo score ≥ III), anastomotic leakage, surgical site infection, bleeding, ileus, urinary complications, respiratory complications, conversion to open surgery, unscheduled reoperation, perioperative mortality, and pathological outcomes, were extracted. The results were analyzed using RevMan v5.3. RESULTS: Seven randomized controlled trials that included 507 robotic and 516 laparoscopic rectal cancer surgery cases were included. Meta-analysis showed that the overall postoperative complications within 30 days [Z = 1.1, OR = 1.18, 95% CI (0.88-1.57), P = 0.27], severe postoperative complications [Z = 0.22, OR = 1.12, 95% CI (0.41-3.07), P = 0.83], anastomotic leakage [Z = 0.96, OR = 1.27, 95% CI (0.78-2.08), P = 0.34], surgical site infection [Z = 0.18, OR = 1.05, 95% CI (0.61-1.79), P = 0.86], bleeding [Z = 0.19, OR = 0.89, 95% CI (0.27-2.97), P = 0.85], ileus [Z = 1.47, OR = 0.66, 95% CI (0.38-1.15), P = 0.14], urinary complications [Z = 0.66, OR = 1.22, 95% CI (0.67-2.22), P = 0.51], respiratory complications [Z = 0.84, OR = 0.64, 95% CI (0.22-1.82), P = 0.40], conversion to open surgery [Z = 1.73, OR = 0.61, 95% CI (0.35-1.07), P = 0.08], unscheduled reoperation [Z = 0.14, OR = 0.91, 95% CI (0.26-3.20), P = 0.89], perioperative mortality [Z = 0.28, OR = 0.79, 95% CI (0.15-4.12), P = 0.78], and pathological outcomes were similar between robotic and laparoscopic rectal surgery. CONCLUSION: Robotic surgery for rectal cancer was comparable to laparoscopic surgery with respect to postoperative complications within 30 days.

Long-term oncological outcomes in robotic versus laparoscopic approach for rectal cancer: A systematic review and meta-analysis.

BACKGROUND: Short-term outcomes of robotic mesorectal excision for rectal cancer resection seem comparable to those of conventional laparoscopic mesorectal excision. However, the long-term oncological outcomes of robot mesorectal excision require further investigation. MATERIALS AND METHODS: The PubMed, EMBASE, Medline, and Cochrane Library databases were searched from the date of database inception to March 31, 2019 for all available trials; the results of robotic and laparoscopic mesorectal excision for rectal cancer surgery were compared. Survival parameters, including overall survival (OS) and disease-free survival (DFS), were independently extracted by two investigators. Hazard ratios (HRs) were calculated using random- or fixed-effects models. The presence of heterogeneity was assessed using Q test, and the extent of heterogeneity was quantified by I2 index. The meta-analysis was performed using Review Manager software, version 5.3. RESULTS: A total of seven studies including 2593 patients (1362 treated by robotic mesorectal excision and 1231 by laparoscopic mesorectal excision) were included. Pooled analyses showed no significant difference in OS (HR = 0.94, 95% confidence interval [CI]: 0.63 to 1.39, P = 0.75) or DFS (HR = 0.93, 95% CI: 0.79 to 1.10, P = 0.85) between the robotic and laparoscopic mesorectal excision for treatment of rectal cancer. CONCLUSION: Regarding long-term survival, robotic mesorectal excision for rectal cancer is comparable to laparoscopic mesorectal excision. More prospective, multicenter randomized trials with longer follow-up periods are needed to determine the long-term outcomes of patients undergoing robotic mesorectal excision.

Mini-invasive vs open resection of colorectal cancer and liver metastases: A meta-analysis.

BACKGROUND: The safety and feasibility of the simultaneous resection of primary colorectal cancer (CRC) and synchronous colorectal liver metastases (SCRLM) have been demonstrated in some studies. Combined resection is expected to be the optimal strategy for patients with CRC and SCRLM. However, traditional laparotomy is traumatic, and the treatment outcome of minimally invasive surgery (MIS) is still obscure. AIM: To compare the treatment outcomes of MIS and open surgery (OS) for the simultaneous resection of CRC and SCRLM. METHODS: A systematic search through December 22, 2018 was conducted in electronic databases (PubMed, EMBASE, Web of Science, and Cochrane Library). All studies comparing the clinical outcomes of MIS and OS for patients with CRC and SCRLM were included by eligibility criteria. The meta-analysis was performed using Review Manager Software. The quality of the pooled study was assessed using the Newcastle-Ottawa scale. The publication bias was evaluated by a funnel plot and the Begg's and Egger's tests. Fixed- and random-effects models were applied according to heterogeneity. RESULTS: Ten retrospective cohort studies involving 502 patients (216 patients in the MIS group and 286 patients in the OS group) were included in this study. MIS was associated with less intraoperative blood loss [weighted mean difference (WMD) = -130.09, 95% confidence interval (CI): -210.95 to -49.23, P = 0.002] and blood transfusion [odds ratio (OR) = 0.53, 95%CI: 0.29 to 0.95, P = 0.03], faster recovery of intestinal function (WMD = -0.88 d, 95%CI: -1.58 to -0.19, P = 0.01) and diet (WMD = -1.54 d, 95%CI: -2.30 to -0.78, P < 0.0001), shorter length of postoperative hospital stay (WMD = -4.06 d, 95%CI: -5.95 to -2.18, P < 0.0001), and lower rates of surgical complications (OR = 0.60, 95%CI: 0.37 to 0.99, P = 0.04). However, the operation time, rates and severity of overall complications, and rates of general complications showed no significant differences between the MIS and OS groups. Moreover, the overall survival and disease-free survival after MIS were equivalent to those after OS. CONCLUSION: Considering the studies included in this meta-analysis, MIS is a safe and effective alternative technique for the simultaneous resection of CRC and SCRLM. Compared with OS, MIS has less intraoperative blood loss and blood transfusion and quicker postoperative recovery. Furthermore, the two groups show equivalent long-term outcomes.

Effectiveness and safety of robotic versus traditional laparoscopic gastrectomy for gastric cancer: An updated systematic review and meta-analysis.

Gastrectomy is considered the gold standard treatment for gastric cancer patients. Currently, there are two minimally invasive surgical methods to choose from, robotic gastrectomy (RG) and laparoscopic gastrectomy (LG). Nevertheless, it is still unclear which is superior between the two. This meta-analysis aimed to investigate the effectiveness and safety of RG and LG for gastric cancer. A systematic literature search was performed using PubMed, Embase, and the Cochrane Library databases until September 2018 in studies that compared RG and LG in gastric cancer patients. Operative and postoperative outcomes analyzed were assessed. The quality of the evidence was rated using the Grading of Recommendations, Assessment, Development and Evaluations. Twenty-four English studies were analyzed. The meta-analysis revealed that the RG group had a significantly longer operation time, lower intraoperative blood loss, and higher perioperative costs compared to the LG group. However, there were no differences in complications, conversion rate, reoperation rate, mortality, number of lymph nodes harvested, days of first flatus, postoperative hospitalization time, and survival rate between the two groups. RG was shown to be associated with decreased intraoperative blood loss and increased perioperative cost and operation time compared to LG. Several higher-quality original studies and prospective clinical trials are required to confirm the advantages of RG.

Risk factors for 30-day unplanned reoperation after pancreatoduodenectomy: A single-center experience.

OBJECTIVE: The purpose of this study was to investigate the rate and reasons and also the risk factors for unplanned reoperation after pancreatoduodenectomy (PD) in a single center. PATIENTS AND METHODS: This retrospective analysis included patients who underwent PD in the First Affiliated Hospital of Nanchang University between January 2010 and January 2018. The patients were divided into nonreoperation and reoperation groups according to whether they underwent unplanned reoperation following the primary PD. The incidence and reasons were examined. In addition, multivariate logistic regression analysis was performed to identify the risk factors for unplanned reoperation. RESULTS: Of the 330 patients who underwent PD operations, 22 (6.67%) underwent unplanned reoperation. The main reasons for reoperation were postpancreaticoduodenectomy hemorrhage (PPH) (12/22 [54.5%]) and pancreaticoenteric anastomotic (PEA) leak (5/22 [22.7%]). Multivariate logistic regression analyses identified that diabetes (odds ratio [OR], 3.70; 95% confidence interval [CI], 1.06-12.90; P = 0.04), intraoperative blood loss ≥400 mL (OR, 4.06; 95% CI, 1.29-12.84; P = 0.02), occurrence of postoperative complications in the form of PPH (OR, 30.67; 95% CI, 8.85-106.31; P < 0.001), and PEA leak (OR, 11.53; 95% CI, 3.03-43.98, P < 0.001) were independent risk factors for unplanned reoperation. CONCLUSIONS: Our results suggest that diabetes, intraoperative blood loss ≥400 mL, PPH, and PEA leak were independent risk factors for unplanned reoperation after primary PD.

Situs inversus totalis with solid pseudopapillary pancreatic tumor: A case report and review of literature.

RATIONALE: Situs inversus totalis (SIT) is a rare anatomical variation of the internal organs, and solid pseudopapillary tumor of the pancreas (SPTP) is a rare tissue type of pancreatic tumors, classified as benign or low-grade malignancy. However, to our knowledge, a patient with SIT and SPTP is extremely rare and has never been reported. PATIENT CONCERNS: We retrospectively analyzed a case of SIT with SPTP in a 45-year-old woman. The main complaints were abdominal pain and sensation of heaviness for 2 weeks. There was tenderness and a mass that could be palpated in the right upper abdomen. DIAGNOSES: Heart ultrasonography (USG), chest x-ray, computed tomography (CT), and contrast-enhanced computerized tomography (CECT) revealed a mirror-image dextrocardia and inversion of all abdominal viscera and a space-occupying lesion in the pancreas tail. Abdominal computed tomography angiography (CTA) showed no obvious abnormality of artery. The diagnosis of SPTP was finally made by postoperative pathological examination. INTERVENTIONS: The patient underwent resection of the pancreatic body and tail and splenectomy via laparotomy to completely remove the tumor. OUTCOMES: The patient was discharged with specific discomfort on postoperative day 7. At the 1.5-year follow-up, she recovered without issue. LESSONS: Surgical resection remains the only effective treatment of SPTP. SIT with SPTP can be accurately diagnosed by heart USG, chest x-ray, CT, and CECT of the upper abdomen. Abdominal aorta CTA before surgery can decrease the injury risk of blood vessels.

Liver transplantation for decompensated liver cirrhosis caused by progressive familial intrahepatic cholestasis type 3: A case report.

RATIONALE: Progressive familial intrahepatic cholestasis (PFIC) type 3, characterized by high gamma glutamyl transferase (GGT), is an autosomal recessive genetic disease. It often occurs in patients' first years of age. However, high GGT type PFIC is still rare. PATIENT CONCERNS: The present study reports a case of liver transplantation for decompensated liver cirrhosis caused by PFIC type 3. An 18-year-old male presented with a history of abdominal distension and jaundice for 2 months. He had abdominal tenderness but no rebounding pain. Moreover, his dullness was felt over the liver and the spleen was palpable 8 cm below the ribs. DIAGNOSES: Computed tomography and magnetic resonance cholangiopancreato graphy of the upper abdomen revealed cirrhosis, portal hypertension, collateral circulation formation, large spleen, and ascites. Blood biochemistry showed high alanine transaminase, aspartate transaminase, and GGT. The diagnosis of decompensated liver cirrhosis caused by PFIC-3 was finally confirmed by plasma gene detecting. INTERVENTIONS: The patient received an open surgery named allogeneic liver transplantation after successful matching of immune types between the recipient and donor. Peritoneal puncture and catheter drainage under B-ultrasound was performed when an encapsulated effusion between the liver and stomach arose. OUTCOMES: The patient was discharged without specific discomfort and was almost free of fluid accumulation 51 days after the surgery. At the 6-month follow-up, he had no discomfort and the blood routine, liver functions showed no abnormalities. LESSONS: We found a new mutant fragment of ABCB4 gene in the process of diagnosis. Liver transplantation remains the most definitive treatment for PFIC. Current medical therapies and surgical interventions such as biliary diversion have potentially created a synergistic outcome.

Lung microenvironment promotes the metastasis of human hepatocellular carcinoma cells to the lungs.

Cancer metastasis is a highly tissue-specific and organ-selective process. It has been shown that the affected tissues and/or organs play a major role in this complex process. The lung is the most common target organ of extrahepatic hepatocellular carcinoma (HCC) metastasis, but the precise molecular mechanism underlying this organ-specific metastasis remains unclear. We hypothesized that lung microenvironment was able to promote the metastasis of HCC cells to the lungs leading to distant metastases. In support of our hypothesis, we provided evidence from targeted metastasis in various types of cancer and contributing factors in the microenvironment of targeted tissues/organs. A better understanding of the steps involved in the interplay between HCC cells and lung microenvironment may offer new perspectives for the medical management of lung metastases of HCC.

Feasibility and safety of laparoscopic liver resection for hepatocellular carcinoma with a tumor size of 5-10 cm.

BACKGROUND: Although laparoscopic liver resection has developed rapidly and gained widespread acceptance for the treatment of benign liver diseases and hepatocellular carcinoma with a small tumor size, its usefulness for the treatment of large tumors is less clear, due to concerns about compromising oncological principles and patient safety. The purpose of this study was to explore the safety and feasibility of laparoscopic liver resection for the treatment of hepatocellular carcinoma with a tumor size of 5-10 cm. METHODS: From March 2007 to December 2011, we performed liver resection in 275 patients with hepatocellular carcinoma with a tumor size of 5-10 cm. Laparoscopic liver resection was performed in 97 patients (Lap-Hx group) and open liver resection was performed in 178 patients (Open-Hx group). Operative time, estimated intraoperative blood loss, blood transfusion rate, and length of postoperative hospital stay were compared between the two groups. Early and intermediate-term postoperative outcomes were also compared. RESULTS: Only one liver resection was performed for every patient with HCC in the present study.No operative deaths occurred in either group. Nine of the laparoscopic procedures were converted to open resection (conversion rate 9.28%). There were no significant differences in mean operative time (245±105 min vs 225±112 min; P = .469), mean estimated intraoperative blood loss (460±426 mL vs 454±365 mL; P = .913), or blood transfusion rate (4.6%, 4/88) vs (2.8%, 5/178)(P = .480) between the Lap-Hx and Open-Hx groups. However, postoperative hospital stay was shorter in the Lap-Hx group than the Open-Hx group (8.2±3.6 days vs 13.5±3.8 days; P = .028). There was a lower rate of postoperative complications in the Lap-Hx group than the Open-Hx group (9% vs 30%; P = .001), but there were no severe complications in either group. The median overall follow-up time was 21 months (range 2-50 months) and the median follow-up of time of survivors was 23 months. The median follow-up time was 25 months in the Lap-Hx group and 20 months in the Open-Hx group. The follow-up rate was 95% (84 patients) in the Lap-Hx group and 95% (169 patients) in the Open-Hx group, which was not a significant difference between the two groups (P = .20). Tumor recurrence occurred in 17 patients (20%) in the Lap-Hx group and 35 patients (21%) in the Open-Hx group, which was not a significant difference between the two groups (P = .876). A total of 33 patients (13%) died during the study period, including 12 patients (14%) in the Lap-Hx group and 21 patients (12%) in the Open-Hx group, which was not a significant difference between the two groups (P = .695). There were also no significant differences in the 1-year rates of overall survival (94% vs 95%; P = .942) or disease-free survival (93% vs 92%; P = .941), or the 3-year rates of overall survival (86% vs 88%; P = .879) or disease-free survival (66% vs 67%; P = .931), between the Lap-Hx and Open-Hx groups. CONCLUSIONS: Laparoscopic liver resection is safe and feasible in patients with hepatocellular carcinoma with a tumor size of 5-10 cm. Laparoscopic liver resection can avoid some of the disadvantages of open resection, and is beneficial in selected patients based on preoperative liver function, tumor size and location.

[Vascular endothelial growth factor receptor-1 activation induces epithelial to mesenchmal transition in hepatocellular carcinoma cell line MHCC97-H.].

OBJECTIVE: To evaluate the mechanism of increased invasion and migration of hepatocellular carcinoma (HCC) cells induced by vascular endothelial growth factor receptor-1 (VEGFR-1) activation. METHODS: Vascular endothelial growth factor-B (VEGF-B) was used to induce and stimulate hepatocellular carcinoma cell line MHCC97-H. Morphologic changes of MHCC97-H were investigated. The expression of E-cadherin and alpha-catenin (two epithelial markers) and Vimentin and N-cadherin (two mesenchymal markers) was detected by reverse transcriptase polymerase chain reaction (RT- PCR), western blotting, and immunofluorescence staining. Cell invasion and migration test was performed. RESULTS: Treatment of MHCC97-H cells with VEGF-B led to morphologic changes characteristic of epithelial to mesenchymal transition (EMT), including loss of polarity, increased intercellular separation, and the presence of pseudopodia. Expression of the epithelial adhesion molecules, including E-cadherin and alpha-catenin, was decreased after VEGF-B treatment. Conversely, an increase in the expression of the mesenchymal cell markers, including N-cadherin and vimentin, was observed after VEGF-B treatment (P less than 0.05). VEGF-B-treated cells exhibited a change in E-cadherin from an organized, membrane-bound structure to a disorganized state in which it was noted to be dispersed throughout the cytoplasm. Pretreatment with VEGFR-1 blocking antibody 18F1 inhibited the change in localization of E-cadherin induced by VEGF-B treatment. The ability of invasion and migration of MHCC97-H was enhanced by VEGF-B reatment (P less alpha 0.05). CONCLUSION: Increased invasion and migration of HCC cells induced by VEGFR-1 activation was mediated by epithelial to mesenchymal transition.

[The expression and significance of vascular endothelial growth factor and its receptors in hepatocellular carcinoma cell lines with various metastatic potentialities].

OBJECTIVES: To examine whether or not vascular endothelial growth factor (VEGF) and its receptors were expressed in hepatocellular carcinoma cell lines with various metastatic potentialities. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR), enzyme linked immunosorbent assay (ELISA) and Western blot were employed to study the expressions of VEGFR-1, VEGFR-2, VEGF-A and VEGF-B in four hepatocellular carcinoma cell lines MHCC97-H, MHCC97-L, SMMC7721 and HepG-2 and one normal liver cell line L-02. RESULTS: Three hepatocellular carcinoma cell lines (MHCC97-H, MHCC97-L, SMMC7721) expressed VEGFR-1 mRNA and their proteins. The expression level of VEGFR-1 in MHCC97-H was higher than that in MHCC97-L (P less than 0.05) and the expression level of VEGFR-1 in MHCC97-L was higher than that in SMMC7721 (P less than 0.05). No expression of VEGFR-1 was found in HepG-2 or L-02. All four hepatocellular carcinoma cell lines and the L-02 cell line expressed VEGFR-2 mRNA and the protein, as well as the VEGFR-1 ligands VEGF-A and VEGF-B. The expression level of VEGFR-2 in all tested hepatocellular carcinoma cell lines and normal liver cell line L-02 showed no significant differences (P more than 0.05). CONCLUSION: VEGFR-1 was expressed in 4 hepatocellular carcinoma cell lines with various metastatic potentialities. The expression levels appeared to be positively correlated with the potentialities of metastasis of the hepatocellular carcinoma cell lines. VEGFR-1 may relate to the invasiveness and metastatic potential of the hepatocellular carcinoma.