Low central venous pressure reduces blood loss in hepatectomy

AIM： To investigate the effect of low central venous pressure （LCVP） on blood loss during hepatectomy for hepatocellular carcinoma （HCC）. METHODS： By the method of sealed envelope, 50 HCC patients were randomized into LCVP group （n=25） and control group （n=25）. In LCVP group, CVP was maintained at 2-4 mmHg and systolic blood pressure （SBP） above 90 mmHg by manipulation of the patient＇s posture and administration of drugs during hepatectomy, while in control group hepatectomy was performed routinely without lowering CVP. The patients＇ preoperative conditions, volume of blood loss during hepatectomy, volume of blood transfusion, length of hospital stay, changes in hepatic and renal functions were compared between the two groups. RESULTS： There were no significant differences in patients＇ preoperative conditions, maximal tumor dimension, pattern of hepatectomy, duration of vascular occlusion, operation time, weight of resected liver tissues, incidence of post-operative complications, hepatic and renal functions between the two groups. LCVP group had a markedly lower volume of total intraoperative blood loss and blood loss during hepatectomy than the control group, being 903.9 ± 180.8 mL vs 2 329.4 ±2 538.4 （W=495.5, P〈0.01） and 672.4±429.9 mL vs 1 662.6±1 932.1 （W=543.5, P〈0.01）. There were no remarkable differences in the pre-resection and post-resection blood losses between the two groups. The length of hospital stay was significantly shortened in LCVP group as compared with the control group, being 16.3±6.8 d vs 21.5 ± 8.6 d （W= 532.5, P〈0.05）.CONCLUSION： LCVP is easily achievable in technique. Maintenance of CVP ≤4 mmHg can help reduce blood loss during hepatectomy, shorten the length of hospital stay, and has no detrimental effects on hepatic or renal function.

Combined vascular resection and analysis of prognostic factors for hilar cholangiocarcinoma

BACKGROUND： Hilar cholangiocarcinoma （HCCA） is a devastating malignancy arising from the bifurcation of the hepatic duct, whether combined vascular resection benefits HCCA patients is controversial. This study was undertaken to assess the effect of combined vascular resection in HCCA patients and to analyze the prognostic factors.

Transplantation of fetal liver epithelial progenitor cells ameliorates experimental liver fibrosis in mice

AIM： To investigate the effect of transplanted fetal liver epithelial progenitor （FLEP） cells on liver fibrosis in mice. METHODS： FLEP cells were isolated from embryonal day （ED） 14 BALB/c mice and transplanted into female syngenic BALB/c mice （n = 60）. After partial hepatectomy （PH）, diethylnitrosamine （DEN） was administered to induce liver fibrosis. Controls received FLEP cells and non-supplemented drinking water, the model group received DEN-spiked water, and the experimental group received FLEP cells and DEN. Mice were killed after 1, 2, and 3 mo, and alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, hyaluronic acid （HA）, and laminin （LN） in serum, and hydroxyproline （Hyp） content in liver were assessed. Alpha-smooth muscle actin （α-SMA） of liver was tested by immunohistochemistry. Transplanted male mice FLEP cells were identified by immunocytochemistry for sty （sex determination region for Y chromosome） protein. RESULTS： Serum ALT, AST, HA, and LN were markedly reduced by transplanted FLEP cells. Liver Hyp content and （α-SMA staining in mice receiving FLEP cells were lower than that of the model group, which was consistent with altered liver pathology. Transplanted cells proliferated and differentiated into hepatocytes and bile duct epithelial cells with 30%-50% repopulation in the liver fibrosis induced by DEN after 3 mo. CONCLUSION： Transplanted FLEP cells proliferate and differentiate into hepatocytes and bile duct epithelial cells with high repopulation capacity in the fiberized liver induced by DEN, which restores liver function and reduces liver fibrosis.

Hepatocyte apoptosis induced by hepatic ischemia-reperfusion injury in cirrhotic rats

OBJECTIVE: To investigate whether hepatocyte apoptosis in hepatic ischemia-reperfusion (I/R) injury is mediated by Fas pathway. METHODS: Fas-mRNA expression detected by in situ hybridization assay, caspase-3 activity measured by fluorescence spectrophotometer, and hepatocyte apoptosis detected by TUNEL assay were compared in different L/R conditions between cirrhotic and normal rats. The relationship was analyzed between hepatocyte apoptosis, Fas-mRNA expression, and caspase-3 activity. RESULTS: In cirrhotic rats, Fas-mRNA expression and caspase-3 activity were significantly increased when the ischemic time prolonged, and subsequently, hepatocyte apoptosis was increased (P<0.O1). Under the same I/R condition, the Fas-mRNA expression, caspase-3 activity and hepatocyte apoptosis in cirrhotic liver were significantly higher than those in normal liver (P<0.O1). CONCLUSIONS: Hepatocyte apoptosis in hepatic I/R injury might be mediated by Fas pathway. The possible underlying mechanism that cirrhotic liver is more sensitive to ischemic injury than normal liver is alteration of Fas expression level.

EYA4 gene functions as a prognostic marker and inhibits the growth of intrahepatic cholangiocarcinoma

Background:The molecular prognostic markers and carcinogenesis of intrahepatic cholangiocarcinoma(ICC) have not been well documented.The purpose of this study was to investigate the prognostic value of the eyes absent homolog 4(EYA4) gene in ICC and its biological effects on ICC growth in vitro and in vivo.Methods:One hundred twelve patients with ICC who underwent hepatectomy were enrolled in the study.EYA4 mRNA and EYA4 protein levels in ICC and adjacent non-tumoral tissues were evaluated using real-time quantitative polymerase chain reaction and immunohistochemical staining,respectively.EYA4 protein levels in ICC cells were determined using western blot analysis.The associations between EYA4 expression and clinicopathologic features of ICC were analyzed.To identify independent prognostic factors,univariate and multivariate analyses were performed.The biological effects of EYA4 on ICC cells were evaluated by establishing stable EYA4-overexpressing transfectants in vitro,and EYA4's effects on tumor growth were evaluated by intra-tumoral injection of EVA4-expressing plasmids in a NOD/SCID murine model of xenograft tumors.Results:ICC tissues had significantly lower EYA4 mRNA and protein levels compared with adjacent non-tumoral tissues(both P < 0.001).Univariate and multivariate analyses showed that EYA4 protein level,tumor number,adjacent organ invasion,lymph node metastasis,and tumor differentiation were independent prognostic factors for diseasefree survival and overall survival(all P < 0.05).In vitro,EYA4 overexpression inhibited tumor cell growth,foci formation,and cell invasiveness.In vivo,intra-tumoral injection of EYA4-expressing plasmids significantly inhibited ICC growth in the murine xenograft model compared with the control group(P < 0.05).Conclusion:EYA4 gene functioned as a molecular prognostic marker in ICC,and its overexpression inhibited tumor growth in vitro and in vivo.

Diagnosis and Treatment of Cholangiocarcinoma: A Consensus from Surgical Specialists of China

Cholangiocarcinoma refers to malignant tumors that develop in epithelial lining of biliary system, and it is divided into two categories according to tumor location, intrahepatic cholangiocarcinoma （ICC） and extrahepatic cholangiocarcinoma （ECC）. ICC occurs from the epithelial cells of the intrahepatic bile duct, its branches and interlobular biliary tree; and ECC is divided into hilar cholangiocarcinoma and distal cholangiocarcinoma by the circumscription at the confluence of cystic duct and the common hepatic duct.

Transplanted bone marrow stromal cells are not cellular origin of hepatocellular carcinomas in a mouse model of carcinogenesis

AIM:To investigate the malignant potential of hepatic stem cells derived from the bone marrow stromal cells (BMSCs) in a mouse model of chemical hepatocarcino- genesis. METHODS:BMSCs from male BALB/c mice were harvested and cultured, then transplanted into female syngenic BALB/ c mice via portal vein. Hepato-carcinogenesis was induced by 6 mo of treatment with diethylnitrosamine (DEN). Six months later, the liver was removed from each treated mouse and evaluated by immunohistochemistry and fluorescence in situ hybridization (FISH). RESULTS:Twenty-six percent of recipient mice survived and developed multiple hepatocellular carcinomas (HCCs). Immunohistochemically, HCC expressed placental form of glutathione-S-transferase (GST-P) and α-fetoprotein, but did not express cytokeratin 19. Y chromosome positive hepatocytes were detected by fluorescent in situ hybridization (FISH) in the liver of mice treated with DEN after BMSCs transplantation while no such hepatocytes were identified in the liver of mice not treated with DEN. No HCC was positive for the Y chromosome by FISH. CONCLUSION:Hepatic stem cells derived from the bone marrow stromal cells have a low malignant potential in our mouse model of chemical hepatocarcingenesis.

Long-term outcome and prognostic factors of combined hepatocellular carcinoma and cholangiocarcinoma after curative resection

Background:Combinedhepatocellular carcinoma and cholangiocarcinoma(cHCC-CC)is a rare subtype of primary liver cancers.Its prognostic factors remain unclear.The study aimed to evaluate its long-termoutcome and prognostic factors by retrospectively reviewing the series of cHCC-CC after curative resection from our institute.Methods:Atotal of 55 pathologically confirmed cHCC-CC patients undergoing curative resections between January 2003 and January 2018 at the First Affiliated Hospital of Sun Yat-sen University(Guangzhou,China)were included.The clinicopathological and follow-up data were retrieved.Overall survival(OS)and recurrence-free survivals(RFS)were analysed by Kaplan–Meier curve.The independent prognostic factors were determined by using univariate andmultivariate Cox analyses.Results:Therewere 41 males and 14 females,with a median age of 51.0(interquartile range,44.0–60.0)years.The 1-,3-,and 5-year OS and RFS rates in cHCC-CC were 80.0%,25.5%,and 16.4%,respectively,and 52.7%,21.8%,and 10.9%,respectively.The median OS and RFS were 24.9 and 14.5 months,respectively.Univariate and multivariate analyses revealed that elevated alpha-fetal protein(AFP)and/or CA19-9,vascular invasion,local extra-hepatic invasion,and lymph-node metastasis(LNM)were independent unfavorable prognostic factors for OS and RFS(all P<0.005).Furthermore,elevated AFP and/or CA19-9 were independent unfavorable prognostic factors in various subgroups of cHCC-CC,including patients aged<60 years,positive hepatitis B surface antigen,cirrhosis,single tumor,tumor size5 cm,no vascular invasion,no LNM,and no local extra-hepatic invasion(all P<0.05).Conclusions:ElevatedAFP and/or CA19-9,vascular invasion,local extra-hepatic invasion,and LNM were independent unfavorable prognostic factors for long-term survival of cHCC-CC undergoing curative resections.Patients with normal levels of AFP and CA19-9 had better prognosis.

Evaluation of the short-term outcomes of robotic-assisted radical resection for perihilar cholangiocarcinoma:a propensity-scored matching analysis

Background:The application of robotic-assisted radical resection in perihilar cholangiocarcinoma(pCCA)remains poorly defined.This study aimed to evaluate the safety and efficacy of robotic-assisted radical resection for pCCA in our institute.Methods:Between July 2017 and July 2022,pCCA patients undergoing robotic-assisted and open radical resection at First Affiliated Hospital of Sun Yat-sen University(Guangzhou,China)were included.The short-term outcomes were compared by using propensity-scored matching(PSM)analysis.Results:Eighty-six pCCA patients were enrolled.After PSM at a ratio of 1:2,10 and 20 patients were assigned to the roboticassisted and open groups,respectively.There were no significant disparities in the clinicopathological features between the two groups.The robotic-assisted group had significantly longer operation time(median:548 vs 353 min,P=0.004)and larger total number of lymph nodes examined(median:11 vs 5,P=0.010)than the open group.The robotic-assisted group tended to have a lower intraoperative blood loss(median:125 vs 350 mL,P=0.067),blood transfusion rates(30.0%vs 70.0%,P=0.056),and post-operative overall morbidities(30.0%vs 70.0%,P=0.056)than the open group,even though the differences were not statistically significant.There were no significant differences in the negative resection margin,post-operative major morbidities,or post-operative length-of-stay between the robotic-assisted and open groups(all P>0.05).Conclusions:Robotic-assisted radical resection of pCCA may get a larger total number of lymph nodes examined than open surgery.Provided robotic-assisted surgery may be a feasible and safe technique for selected pCCA patients.

Values of debulking surgery for unresectable well-differentiated metastatic pancreatic neuroendocrine tumors:a comparative study

Background and objective:The value of debulking surgery for unresectable well-differentiated metastatic pancreatic neuroendocrine tumor(m-PNET)remains poorly defined.This study aimed to evaluate the outcomes of m-PNET following debulking surgery in our institute.Methods:Patients with well-differentiated m-PNET in our hospital between February 2014 and March 2022 were collected.Clinicopathological and long-term outcomes of patients treated with radical resection,debulking surgery,and conservative therapy were compared retrospectively.Results:Fifty-three patients with well-differentiated m-PNET were reviewed,including 47 patients with unresectable m-PNET(debulking surgery,25;conservative therapy,22)and 6 patients with resectable m-PNET(radical resection).Patients undergoing debulking surgery had a post-operative Clavien–DindoIII complication rate of 16.0%without mortality.The 5-year overall survival(OS)rate of patients treated with debulking surgery was significantly higher than that of those treated with conservative therapy alone(87.5%vs 37.8%,log-rank P=0.022).Besides,the 5-year OS rate of patients treated with debulking surgery was comparable to that of patients with resectable m-PNET undergoing radical resection(87.5%vs 100%,log-rank P=0.724).Conclusions:Patients with unresectable well-differentiated m-PNET who underwent resection had better long-term outcomes than those who received conservative therapy alone.The 5-year OS of patients undergoing debulking surgery and radical resection were comparable.Debulking surgery could be considered for patients with unresectable well-differentiated m-PNET if no contraindication exists.

Values of spleen-preserving distal pancreatectomy in well-differentiated non-functioning pancreatic neuroendocrine tumors:a comparative study

Background The feasibility of spleen-preserving distal pancreatectomy(SPDP)to treat well-differentiated non-functioning pancreatic neuroendocrine tumors(NF-pNETs)located at the body and/or tail of the pancreas remains controversial.Distal pancreatectomy with splenectomy(DPS)has been widely applied in the treatment of NF-pNETs;however,it may increase the post-operative morbidities.This study aimed to evaluate whether SPDP is inferior to DPS in post-operative outcomes and survivals when being used to treat patients with NF-pNETs in our institute.Methods Clinicopathological features of patients with NF-pNETs who underwent curative SPDP or DPS at the First Affiliated Hospital of Sun Yat-sen University(Guangzhou,China)between January 2010 and January 2022 were collected.Short-term outcomes and 5-year survivals were compared between patients undergoing SPDP and those undergoing DPS.Results Sixty-three patients(SPDP,27;DPS,36)with well-differentiated NF-pNETs were enrolled.All patients had grade 1/2 tumors.After identifying patients with T1–T2 NF-pNETs(SPDP,27;DPS,15),there was no disparity between the SPDP and DPS groups except for tumor size(median,1.4 vs 2.6 cm,P=0.001).There were no differences in operation time(median,250 vs 295 min,P=0.478),intraoperative blood loss(median,50 vs 100 mL,P=0.145),post-operative major complications(3.7%vs 13.3%,P=0.287),clinically relevant post-operative pancreatic fistula(22.2%vs 6.7%,P=0.390),or post-operative hospital stays(median,9 vs 9 days,P=0.750)between the SPDP and DPS groups.Kaplan–Meier curve showed no significant differences in the 5-year overall survival rate(100%vs 100%,log-rank P>0.999)or recurrence-free survival(100%vs 100%,log-rank P>0.999)between patients with T1–T2 NF-pNETs undergoing SPDP and those undergoing DPS.Conclusions In patients with T1–T2 well-differentiated NF-pNETs,SPDP could achieve comparable post-operative outcomes and prognosis compared with DPS.