Prognostic outcomes of salvage liver transplantation under different transplantation criteria / 中华器官移植杂志

Objective:To compare the prognoses of salvage liver transplantation fulfilling the Criteria of Milan, University of California San Francisco(UCSF)and Hangzhou.Methods:Clinical data were retrospectively reviewed for 256 patients with recurrent hepatocellular carcinoma(HCC)undergoing donation after citizen death(DCD)liver transplantation(LT)from January 2015 to October 2019.They were divided into two groups of primary(PLT, n=175)and salvage(SLT, n=81). General profiles, tumor pathological characteristics and postoperative complications of two groups were compared by T-test, rank-sum or χ2 test.Kaplan-Meier method and Log rank test were employed for comparing overall survival rate(OS)and recurrence-free survival rate(RFS)between two groups.In SLT group, 31 cases fulfilled Milan criteria, 45 cases UCSF criteria and 69 cases Hangzhou criteria.OS/RFS of three groups were compared.According to there was downstaging or bridging treatment pre-LT, SLT group was divided into downstaging group(n=32)and non-downstaging group(n=49). OS/RFS of two groups were compared.According to the Rescit1.1 criteria, downstaging group were divided into remission group(n=14)and non-remission group(n=18)and OS/RFS of two groups were compared. Results:The operative durations of PLT and SLT groups were(439.5±74.9)and(475.1±83.4)min respectively.There was significant inter-group difference( P<0.05); However, no significant inter-group difference existed in amount of intraoperative bleeding, blood transfusion, postoperative hospital stay or incidence of postoperative complications(all P>0.05). No significant difference existed in OS/RFS between PLT and SLT groups( P>0.05). No significant difference existed in OS at 1/3/5 years post-SLT among Milan, UCSF and Hangzhou criteria groups(all P>0.05); However, RFS in Milan criteria group at 1/3/5 years post-SLT were 93.5%, 81.7% and 81.7% respectively.They were significantly higher than 68.9%, 59.7% and 59.7% in UCSF criteria group and 78.3%, 58.8% and 55.5% in Hangzhou criteria group(all P<0.05). For patients on downstaging therapy, OS in the Remission group at 1, 3 and 5 years post-SLT were 100%, 73% and 73% respectively, which was significantly higher than 83.3%, 49.4% and 0 in non-Remission group( P=0.042). RFS in the Remission group at 1, 3 and 5 years post-SLT were 100%, 62.5% and 46.9% respectively, which was significantly higher than 52.9%, 0 and 0 in no-Remission group( P=0.001). Conclusions:The survival outcome of SLT recipients is similar to that of PLT recipients.The overall survival of SLT recipients shows no significant difference between Milan, UCSF and Hangzhou criteria.However, SLT recipients fulfilling Milan criteria have the longest recurrence-free time.The prognosis of patients with remission after preoperative descending treatment is superior to that of patients without remission.

Rapamycin enhances the anti-tumor activity of cabozantinib in cMet inhibitor-resistant hepatocellular carcinoma / 医学前沿

Cabozantinib, mainly targeting cMet and vascular endothelial growth factor receptor 2, is the second-line treatment for patients with advanced hepatocellular carcinoma (HCC). However, the lower response rate and resistance limit its enduring clinical benefit. In this study, we found that cMet-low HCC cells showed primary resistance to cMet inhibitors, and the combination of cabozantinib and mammalian target of rapamycin (mTOR) inhibitor, rapamycin, exhibited a synergistic inhibitory effect on the in vitro cell proliferation and in vivo tumor growth of these cells. Mechanically, the combination of rapamycin with cabozantinib resulted in the remarkable inhibition of AKT, extracellular signal-regulated protein kinases, mTOR, and common downstream signal molecules of receptor tyrosine kinases; decreased cyclin D1 expression; and induced cell cycle arrest. Meanwhile, rapamycin enhanced the inhibitory effects of cabozantinib on the migration and tubule formation of human umbilical vascular endothelial cells and human growth factor-induced invasion of cMet inhibitor-resistant HCC cells under hypoxia condition. These effects were further validated in xenograft models. In conclusion, our findings uncover a potential combination therapy of cabozantinib and rapamycin to combat cabozantinib-resistant HCC.

Imaging anatomical features of donor liver blood vessels in laparoscopic left lateral donor liver acquisition and clinical significance / 中华消化外科杂志

Objective:To investigate the imaging anatomical features of donor liver blood vessels in laparoscopic left lateral donor liver acquisition and their clinical significance.Methods:The retrospective and descriptive study was conducted. The clinical data of 39 living donor liver transplantation (LDLT) donors who were admitted to Huashan Hospital Affiliated to Fudan University between October 2016 and December 2018 were collected. There were 10 males and 29 females, aged (31±7)years. The clinical data of 39 LDLT recipients were collected. There were 26 males and 13 females, aged 8 months (range, 4-68 months). Abdominal enhanced computed tomography and three-dimensional vascular reconstruction were performed on donors to evaluate the anatomical characteristics of hepatic vessels. All the donors underwent laparoscopic left lateral donor liver acquisition. Observation indicators: (1) three-dimensional vascular reconstruction of preoperative imaging; (2) surgical conditions; (3) follow-up. Follow-up was performed using outpatient examination to detect complications of recipients after LDLT up to October 2019. Measurement data with normal distribution were expressed as Mean± SD, and comparison between groups was analyzed by the t test. Measurement data with skewed distribution were represented as M (range). Count data were expressed as absolute numbers or percentages. Results:(1) Three-dimensional vascular reconstruction of preoperative imaging: the anatomical characteristics of hepatic artery and hepatic vein revealed by three-dimensional vascular reconstruction of preoperative imaging of 39 donors included ① middle hepatic artery was present in 11 donors, among which 5 started from the right hepatic artery, 3 from the confluence of the right and left hepatic artery, and 3 from the left hepatic artery. Two donors had anatomical variation in the left hepatic artery which was presentation of left accessory hepatic artery originated from the left gastric artery. The other 26 donors had no middle hepatic artery or anatomical variation in the left hepatic artery. ② The left hepatic vein and the middle hepatic vein of 9 donors were respectively drained into the inferior vena cava. Seven donors had the left upper branch of the left hepatic vein, and 23 donors had a joint trunk of the left hepatic vein and the middle hepatic vein which drained into the inferior vena cava. (2) Surgical conditions: ① all the 39 donors successfully underwent laparoscopic left lateral donor liver acquisition. The operation time and volume of intraoperative blood loss were (160±32)minutes and (142±74)mL. ② Of 11 donors with middle hepatic artery, left hepatic artery was the dominant artery in 8 donors and was used for hepatic artery anastomosis and reconstruction in liver transplantation, middle hepatic artery started from left hepatic artery in 3 donors and the joint trunk of left and middle hepatic artery was used for hepatic artery anastomosis and reconstruction in liver transplantation. Of 2 donors with anatomical variation in the left hepatic artery, one had left accessory hepatic artery as the dominant artery and the other had left hepatic artery as the dominant artery. Left accessory hepatic artery and left hepatic artery were respectively used for hepatic artery anastomosis and reconstruction in liver transplantation. The other 26 donors had left hepatic artery for hepatic artery anastomosis and reconstruction in liver transplantation. ③ Among the 39 donors, 11 received intraoperative left hepatic vein preferred approach and 28 received intraoperative non-left hepatic vein preferred approach. The operation time and volume of intraoperative blood loss of donors with left hepatic vein preferred approach were (147±22)minutes and (110±44)mL, respectively, versus (169±33)minutes and (154±81)mL of donors with non-left hepatic vein preferred approach, showing significant differences in the above indicators between the two groups ( t=4.19, 2.81, P<0.05). (3) Follow-up: 39 donors were followed up for 10 months. During the follow-up, there was no hepatic artery anastomotic bleeding, stenosis, ischemic bile duct injury and biliary stenosis caused by poor hepatic arterial blood supply, or any complications related to hepatic venous outflow tract stenosis. Conclusions:Three-dimensional vascular reconstruction before laparoscopic left lateral donor liver acquisition can reveal the anatomical variation of middle hepatic artery and left hepatic artery, which can guide the selection of surgical approach. The left hepatic vein preferred approach is recommended for the qualified donor in the laparoscopic left lateral donor liver acquisition, which can shorten the operation time and reduce the volume of intraoperative blood loss.

Effect and mechanism of liver X receptor agonist T0901317 on angiogenesis phenotype of liver cancer / 中华消化外科杂志

Objective To explore the effect and mechanism of liver X receptor agonist T0901317 on angiogenesis phenotype of liver cancer.Methods The experimental study was conducted.Hepatocellular carcinoma MHCC97-H and Huh7 cells and human umbilical vein endothelial cells (HUVEC) were cultured in vitro.Each cell line was divided into 3 groups:control group (non-treated),low concentration group (treated using 1 μmot/L T0901317) and high concentration group (treated using 3 μmol/L T0901317).Cell proliferation was counted with a CCK-8 assay.Quantitative real-time polymerase chain reaction (PCR) was applied to confirm the relative mRNA expression of fatty acid synthetase (FAS) of liver X receptor target genes in 3 groups.Subcutaneous xenograft tumor volume and body mass were measured in MHCC97-H nude mice model.Then mice were sacrificed and tumor tissues were analyzed for CD31 relative expression by immunohistochemistry (IHC) staining.Migration and vessel angiogenesis of HUVEC were determined by Transwell method.Observation indicators:(1) effects of T0901317 on MHCC97-H,Huh7 and HUVEC cells proliferation,(2) effects of T0901317 on liver X receptor with MHCC97-H,Huh7 and HUVEC cells,(3) effects of T0901317 on subcutaneous xenograft tumor growth in MHCC97-H nude mice model,(4) effects of T0901317 on CD31 relative expression in subcutaneous xenograft tumor tissues of MHCC97-H nude mice model,(5) effects of T0901317 on migration of HUVEC,(6) effects of T0901317 on vessel angiogenesis of HUVEC.Measurement data with normal distribution were represented as x±s,and comparisons between groups were analyzed by the t test.Results (1)Effects of T0901317 on MHCC97-H,Huh7 and HUVEC cells proliferation:results of CCK-8 assay showed that percentage of living cells was respectively 100.0％± 1.7％,101.0％±0.7％ and 104.6％± 1.9％ in MHCC97-H control,low concentration and high concentration groups,with no statistically significant difference (F =2.632,P＞0.05).Percentage of living cells was respectively 100.0％ ± 2.7％,97.6％ ± 2.4％ and 103.7％ ± 2.8％ in Huh7 control,low concentration and high concentration groups,with no statistically significant difference (F =1.404,P＞0.05).Percentage of living cells was respectively 100.0％ ±0.7％,100.7％± 1.2％ and 101.3％ ±0.8％ in HUVEC control,low concentration and high concentration groups,with no statistically significant difference (F=0.471,P＞0.05).(2) Effects of T0901317 on liver X receptor with MHCC97-H,Huh7 and HUVEC cells:results of quantitative real-time PCR showed that relative mRNA expressions of FAS in MHCC97-H control,low concentration and high concentration groups were respectively 100.0 ％±2.2％,658.5％±7.7％ and 1 241.0％± 106.8％,with a statistically significant difference among groups (F=46.227,P＜0.05),and with a statistically significant difference between MHCC97-H control group and MHCC97-H low concentration and high concentration groups (t =70.025,8.274,P ＜ 0.05) and between MHCC97-H low concentration and high concentration groups (t =4.222,P ＜ 0.05).Relative mRNA expressions of FAS in Huh7 control,low concentration and high concentration groups were respectively 100.0％ ± 15.8％,1 225.0％ ± 26.7 ％ and 2 015.0％ ± 215.1％,with a statistically significant difference among groups (F =49.402,P＜ 0.05),and with a statistically significant difference between Huh7 control group and Huh7 low concentration and high concentration groups (t=39.460,8.879,P＜0.05) and between Huh7 low concentration and high concentration groups (t =2.836,P ＜ 0.05).Relative mRNA expressions of FAS in HUVEC control,low concentration and high concentration groups were respectively 100.0％ ± 19.6％,790.8％ ± 116.5％ and 1 756.0％ ± 55.0％,with a statistically significant difference among groups (F=185.395,P＜0.05),and with a statistically significant difference between HUVEC control group and HUVEC low concentration and high concentration groups (t =7.639,34.375,P＜0.05) and between HUVEC low concentration and high concentration groups (t =7.488,P＜0.05).(3) Effects of T0901317 on subcutaneous xenograft tumor growth in MHCC97-H nude mice model:results of assay showed that subcutaneous xenograft tumor volume in MHCC97-H control group and MHCC97-H T0901317 group were respectively (935±72)mm3 and (552 ± 47)mm3,with a statistically significant difference between groups (t=4.449,P＜0.05).Body masses of nude mice model in MHCC97-H control group and MHCC97-H T0901317 group were respectively (23.8±0.8) g and (21.7± 1.7) g,with no statistically significant difference between groups (t =1.059,P＞0.05).(4) Effects of T0901317 on CD31 relative expression in subcutaneous xenograft tumor tissues of MHCC97-H nude mice model:results of IHC staining showed that CD31 relative expression in subcutaneous xenograft tumor tissues of MHCC97-H nude mice model was 100％±11％ and 35％±7％ in MHCC97-H control group and MHCC97-H T0901317 group,with a statistically significant difference between groups (t =4.919,P＜0.05).(5) Effects of T0901317 on migration of HUVEC:results of Transwell method showed that percentages of membrane cells in HUVEC control,low concentration and high concentration groups were respectively 100.0％±4.0％,57.3％±1.5％ and 32.7％± 1.7％,with a statistically significant difference among groups (F=163.944,P＜0.05),and with statistically significant differences between HUVEC control group and HUVEC low concentration and high concentration groups (t =9.998,15.434,P＜0.05) and between HUVEC low concentration and high concentration groups (t =10.801,P ＜ 0.05).(6) Effects of T0901317 on vessel angiogenesis of HUVEC:results of vessel angiogenesis assay showed that length of vessel angiogenesis in HUVEC control,low concentration and high concentration groups were respectively 100.0％±3.4％,68.4％ ±3.5％ and 44.7％± 0.5％,with a statistically significant difference among groups (F =38.964,P ＜ 0.05),and with statistically significant differences between HUVEC control group and HUVEC low concentration and high concentration groups (t=6.268,9.831,P＜0.05) and between HUVEC low concentration and high concentration groups (t =3.460,P＜0.05).Conclusion Liver X receptor agonist T0901317 can inhibit vessel angiogenesis of liver cancer.

Application of the exosome in diagnosis and treatment of digestive system cancers / 中华消化外科杂志

The concept of precision medicine and precision oncology has been widely accepted.However,the application of this concept still faces many challenges.Exosome investigation is a hot spot in the field of liquid biopsy.Exosomes are extracellular vesicles composed of a lipid bilayer and contain proteins and nucleic acids which regulate cell-cell communication.Exosomes can be isolated and enriched in various body fluids.It has the advantages of micro-invasive,stable and biological active,and it fits well with the practice of precision medicine.In this review,authors discussed potential application and challenge of exosomes in early diagnosis and metastasis monitoring of gastric cancer.

Research hotspots and updates of diagnosis and treatment of hepatocellular carcinoma from 2017 annual meeting of the American Society of Clinical Oncology / 中华消化外科杂志

There were many progressions of hepatocellular carcinoma (HCC) in the 2017 annual meeting of the American Society of Clinical Oncology (ASCO).(1) Sorafenib has been at the heart of treatment for advanced HCC,meanwhile,it has been confirmed to effectively prolong the life time of patients and improve the clinical efficacies combined with other therapies.A variety of molecular and clinical indicators also help screening out peoples.(2) New molecular targeted drugs have sprung up,and Lenvatinib (multiple receptor tyrosine kinases inhibitor) is expected to become the next first-line drug.The second-line Regorafenib has obtained supporting evidence from evidencebased medicine,and a combination therapy of Sorafenib and Regorafenib promises to be a new model of targeted therapy for HCC.However,the phase Ⅲ study (METIV-HCC) of which Tivatinib (ARQ 197) becomes the second-line drug for HCC has failed.(3) Immunization therapy remains a hotspot for HCC.The monoclonal antibodies of immunological checkpoint and adoptive immunotherapy have better safety and clinical efficacy.(4) Primary lesions resection of HCC and drug control of metastatic lesions are expected to be the therapy model for metastatic HCC.The liver transplantation for primary HCC will be further developed.(5) The combination and sequential application of multiple therapies will become an inevitable choice,and efficacy of stereotactic body radiation therapy is expected.The combination and sequential application of transcatheter arterial chemoembolization (TACE) and other therapies is still a main therapy for unresectable HCC.(6) The new predictors and models of prognosis have been popping up,nevertheless,its therapy effects should be further proven.

Isolation, culture and identification of hepatocellular carcinoma-associated fibroblast and its effect on the biological function of hepatocellular carcinoma cells / 肿瘤研究与临床

Objective To establish an in vitro isolation and culture system for hepatocellular carcinoma (HCC)-associated fibroblast (CAF) and identify based on its specific markers of CAF. Methods CAF was isolated from the tumor tissue of the HCC patients after hepatectomy, by digesting with collagenase enzyme, centrifugation and resuspension. The morphology of CAF was observed by electron microscopy. Immunofluorescence staining was performed for detecting α-SMA and fibronectin as well as other specific markers such as AFP on the surface of HCC cells and CD31 on the surface of vascular endothelial cells. On the basis of the study, the function work between CAF and HCC cell line Huh7, HepG2 was detected under co-culture system. Meanwhile, CCK-8 was used to observe the effect of CAF on the proliferation of Huh7 and HepG2 cells, and Transwell assay was used to analyze CAF effect on the invasion of Huh7 and HepG2 cells. Results Compared with the other cells, the morphological analysis showed that CAF was more elongated or spindle-shaped. Moreover, the cell size and the nucleus were larger than normal epithelial cells. Immunofluorescence staining revealed that the CAF surface specific markers including α-SMA and fibronectin were positive, and mainly were the cell membrane staining. The proliferation and invasion of Huh7 and HepG2 were significantly increased by CAF. The results show that the increasing percentage of cells in 24 hours between blank group and the experimental group was (63 ± 4) %, (78 ± 5) % and (69 ± 5) %, (81 ± 3) %respectively after co-culture with CAF, the difference was statistically significant (P<0.05). In transwell model, the number of cells in the blank group and the experimental group was (59.4 ± 3.1), (162.9 ± 3.9) and (104.8 ± 2.6), (166.4 ± 4.2), and the difference was also statistically significant (P< 0.05). Conclusion The isolated CAF from HCC enhances the ability of tumor's proliferation and invasion.

Hepatocyte growth factor/c-Met signaling pathway decreases doxorubicin sensitivity in hepatocellular carcinoma in vitro / 肿瘤研究与临床

Objective To explore the effect of hepatocyte growth factor (HGF)/c-Met signaling in doxorubicin (DOX) treatment of hepatocellular carcinoma (HCC). Methods Different biologic and genetic characteristics human HCC cell lines, Huh7, HepG2, MHCC97-L and MHCC97H were used in this experiment. Variation in c-Met mRNA expression level among different HCC cell lines was analyzed by RT-PCR. Western blot analysis was performed to detect c-Met and p-Met expression levels in these cell lines. CCK-8 experiment was carried to analyze the DOX sensitivity in various cell lines. t test and repeated measure analysis of variance were used for statistical analysis. Results Both c-Met and p-Met were overexpressed in MHCC97-L and MHCC97-H cell lines and these cell lines were resistant to DOX compared to Huh7 and HepG2. However, treatment of HGF in Huh7 and HepG2 cells activated c-Met signaling pathway and decreased the sensitivity of these two cell lines to DOX [inhibition rate: Huh7 (34.848 ±5.370) vs. (66.409±5.792)%, HepG2 (34.351±3.305) %vs. (62.308±5.453) %, both P=0.002]. Whereas administration of c-Met inhibitor in MHCC97-L and MHCC97-H cell lines significantly increased the sensitivity to DOX [inhibition rate: MHCC97-L (73.106 ±3.472) % vs. (13.636 ±4.097) %; MHCC97-H (64.444 ±4.006) % vs. (6.296 ±2.796) %, both P< 0.001]. Conclusion HGF/c-Met signaling pathway is related the treatment efficacy of DOX in HCC.

Mutations detection of circulating tumor DNA in patients with hepatocellular carcinoma and its clinical significance / 国际外科学杂志

Mutations detection of circulating tumor DNA can be divided into quantitative and qualitative classifications:the forumer mainly detects the total amount of circulating DNA (serum or plasma),whereas the latter mainly detects the specific genetic variations in serum or plasma DNA,such as gene mutations,methylations of tumor suppressor genes,and microsatellite alterations,etc.Both of them may reflect the tumor presence and disease severity.In this paper,mutations detection and its clinical significance of circulating tumor DNA in patients with hepatocellular carcinoma are reviewed.

Phenotype and distribution of infiltrating lymphocytes in liver cancer tissues / 中国肿瘤临床

Objective:To identify the signature of tumor-infiltrating lymphocyte (TIL) subtypes that may affect cytokine expres-sion between different outcomes of hepatocellular carcinoma (HCC) patients by analyzing the CD molecular expression profiles of non-cancerous hepatic tissues. Methods:Surface markers of TIL in noncancerous hepatic tissues from 146 HCC patients were determined by using immunohistochemical method and flow cytometry. Univariate and multivariate Cox proportional hazards models and Kaplan-Meier method were used to analyze the association of their expression levels with tumor recurrence and survival. Results:More than 86.4%of TILs in patients were quiescent, as measured via CD4+or Foxp3 expression. Meanwhile, more than 90%of CD3+T cells ex-pressed CD8+. The proportion of T cells was low compared with CD8+T cells. The proportion of CD19 and CD20 in distant nontumor tissues almost was zero. The proportion of T cell subgroups isolated from HCC circulating whole blood did not show a significant shift compared with the normal control, as follows:CD4+T/CD8+T=1.167 ± 1.04, CD8+T/CD3+T=0.288 ± 0.116, and CD4+T/CD3+T=0.429 ± 0.178. The proportion of CD8+T cells in noncancerous hepatic tissues was higher than that in blood (P<0.001).Conclusion:TILs in HCC noncancerous hepatic tissues are increased and contain a subpopulation of CD3+CD8+T cells. CD8+T cells in cancerous tissues, rather than noncancerous tissues, show significant differences between different prognostic groups.

Prognosis and management of recurrent primary clear cell carcinoma of liver / 中华肝胆外科杂志

Objective To evaluate the prognosis and management of recurrent primary clear cell carcinoma of liver (PCCCL).Methods 214 patients with PCCCL treated by curative resection from January 1996 to March 2006 were retrospectively studied.Tumour recurrences were classified into early (≤1 year) and late (＞1 year) recurrences.Results Of 99 patients who developed recurrences,28 developed early recurrence while 71 developed late recurrence.The patients with recurrences were treated with re-resection (n=33),percutaneous ethanol injection (PEI,n=7),radiofrequency ablation (RFA,n=10),transcatheter arterial chemoembolization (TACE,n =27),systemic chemotherapy (n=1),Chinese medicine (n=1),and conservative management (n=20).The re-resection rate was higher in the late than in the early recurrence group (P=0.04).In this study,reresection,PEI,and RFA were considered as curative therapies.There was no significant difference in the overall survival (OS) for patients who received these different curative therapeutic procedures (P=0.68).The 1,3-,and 5-year OS of patients with recurrences who were treated with curative treatment were comparable to those patients who did not develop recurrences (100％,86.0％,63.5％ vs 85.2％,72.2％,64.3％,P=0.71).The 1-,3-,and 5-year OS of patients who received TACE for recurrences were 100％,66.7％,and 44.4％ respectively.The results were poorer than patients who received curative treatment for recurrences (P=0.03),but were better than those who received conservative management after recurrences (80.0 ％,25.0 ％,and 10.0 ％,P＜ 0.01).Conclusions Reresection,PEI and RFA are optimal curative methods for recurrent PCCCL.TACE plays an important role in the management of patients with recurrent PCCCL who cannot be treated with curative methods.

Multivariate analysis of risk factors of early and late recurrences after resection for primary clear cell carcinoma of liver / 中华肝胆外科杂志

Objective To investigate the risk factors influencing early and late recurrences after resection of primary clear cell carcinoma of the liver (PCCCL).Methods 214 PCCCL patients treated by curative resection from January 1996 to March 2006 were retrospectively analyzed.Recurrences were classified into early (≤1 year) and late (＞1 year) recurrences.Results 99 patients developed recurrences,with early recurrence in 28 patients and late recurrence in 71 patients.The 3-and 5-year overall survival (OS) rates for recurrent PCCCL were significantly worse than those with no recurrence (68.7％ and 46.2％ vs 72.2％ and 64.3％,P=0.003).The 1-,3-and 5-year OS rates for late recurrence were 100％,80.3％ and 54.6％,which were significantly better than those with early recurrence (85.7％,39.3％ and 25.0％,P=0.001).On multivariate analysis,aminoleucine transferase (ALT) level and vascular invasion were independent risk factors for early recurrence,while age was the only significant risk factor for late recurrence.Conclusions The time to recurrence was the main determinant for prognosis of recurrent PCCCL,Clarifying the different risk factors for early and late recurrences will help postoperative follow-up,early detection of recurrence,and hopefully will improve survival.

Primary clear cell carcinoma of the liver / 中华普通外科杂志

Objective To investigate the clinicopathologic characteristics and prognostic factors of primary clear cell carcinoma of the liver(PCCCL). Methods A total of 214 PCCCL patients treated by curative resection from January 1996 to March 2006 were retrospectively analyzed. Results The 1-,3-,and 5-year overall survival (OS) rates for PCCCL patients were significantly better than those of non-clear cell hepatocellular carcinoma ( NHCC ) patients ( 90.2％,70.6％,and 55.9％ vs 82.8％,62.7％ and 47.7％,P =0.001 ).Tumor size was significantly smaller in PCCCL group than in NHCC group ( x2 =4.37,P =0.04 ).Tumors of PCCCL group had a lower incidence of vascular invasion ( x2 =9.42,P =0.002) and a better differentiation than those of NHCC group ( x2 =4.30,P =0.04).Serum a-fetoprotein (AFP) level,tumor size,liver cirrhosis,and vascular invasion were independent risk factors impacting OS and disease-free survival (DFS) of PCCCL. Conclusions PCCCL is an uncommon subtype of HCC and has different clinicopathologic characteristics from NHCC. Complete surgical resection is the optimal treatment for PCCCL and its prognosis is much better than that of NHCC.

Value of the conventional liver function tests in the assessment of hepatic reserve / 中华肝胆外科杂志

Objective To study the risk factors of post-hepatectomy hepatic decompensation (PHD) in patients with hepatocellular carcinoma.MethodWe reviewed 562 patients with Child-Pugh A classification,who underwent partial hepatectomy for hepatocellular carcinoma at Zhongshan Hospital,Fudan University between July 1st 2007 to December 31st 2007,to study the risk factors of hepatic decompensation.ResultsPreoperative high total bilirubin (TB) and low prealbumin (PA) were independent risk factors of PHD by logistic multivariate analysis ROC analysis revealed the cut-offs of preoperative PA predicting PHD were 0.14 g/L (sensitivity 41.4％; specificity 83.1％).The incidence of PHD was 16.0％ when TB≥20.4 μmol/L and PA＜0.14 g/L(OR=7.276,P=0.002).ConclusionThe Child-Pugh A patients recovered well when the preoperative liver function was as follows:TB＜20.4 μmol/L and PA≥0.14 g/L.

Techniques of anatomical liver resection for hepatocellular carcinoma:a report of 125 cases / 中华消化外科杂志

Objective To summarize the techniques of anatomical liver resection for the treatment of hepatocellular carcinoma(HCC).Methods The clinical data of 125 patients with solitary HCC who underwent anatomical liver resection at the Zhongshan Hospital from January 2005 to December 2006 were retrospectively analysed.The inflow and outflow of hepatic segments to be resected were selectively clamped,then the main branches of portal vein and hepatic artery were ligated,and the ischemic hepatic segments were resected en bloc.Kelly forceps were used to crash and clamp the liver cut surface.The stumps of left and right hepatic ducts were continuously sutured with Prolene sutures.For tumors with the size above 10 cm in diameter,hepatectomy with anterior approach and liver hanging maneuver were adopted.Bile leakage was checked by injecting methylene blue or covering a gauze on the liver cut surface.Results The mean blood loss of all patients was 250 ml(100-6000 ml),and 32 of them needed blood transfusion.The morbidity was 23%(29/125).No patient died within 30 days after the operation,and 6%(5/83)of patients were found with residual tumor by postoperative arteriography.Conclusion Anatomical liver resection may improve the safety of operation,prevent the injury of great vessels and thus improve the efficacy.

Surgical treatment of primary hepatoeellular carcinoma: a 20-year clinical experience in 7566 patients / 中华消化外科杂志

Objective To summarize the clinical experienee in surgical treatment for hepatocellular carcinoma (HCC). Methods The clinical data of 7566 HCC patients who had been admitted to Research Institute of Liver Cancer of Fudan University from January 1988 to Deeember 2007 were retrospectively analyzed. The overall survival and recurrence free survival (RFS) rates were eaeulated with Kaplan-Meier survival curve. All the data were analyzed using Log-rank test and Cox regression model. Results The 3-, 5-, 10-year overall survival and RFS rates of 7164 patients with HCC resection were 56.29%, 41.76%, 26.70%, and 63.92%, 56.12%, 42.97%, respectively, and the perioperative mortality was 1.54%. The 5- and 10-year overall survival rates of patients with small HCC (diameter<5 era) were 58.20% and 38.47%, which were significantly higher than 31.42% and 20.43% of patients with large HCC (diameter >5 cm) (X2 =535. 568, P <0.01). The 5-year overall survival rotes of HCC patients with resection after down-staging (n = 110), re-resection after recurrence (n = 515), and tumor thrombus in portal vein (n = 168) were 51.26%, 67.28% and 26.81%, respectively; nd the 5-year DFS rotes were 77.44%, 13.01% (calculated from the first operation) and 34.90%, respectively. The 3- and 5-year overall survival and DFS rates of 402 patients who had undergone liver transplantation were 60.81%, 55.63% and 64.47%, 58.52%. The independent prognostic factors influencing the overall survival and DFS rates were the size, number and differentiation of HCC and intrahepatic vessel invasion (X2 = 200.539, 27. 536, 96.964,216. 156, P <0.01). Conclusions Early screening, improved safety of surgery, combined therapy and breakthrough in the reseaeh of preventing HCC metastasis and reeurrenee will significantly improve the treatment outcome of HCC.

Overexpression and Effect on Apoptosis of the 150-ku Oxygen-regulated Protein(ORP150) in Human Hepatocellular Carcinoma / 生物化学与生物物理进展

In previous study, the 150-ku oxygen-regulated protein(ORP150) was identified as a candidate glycoprotein related to hepatocellular carcinoma.In order to further validate the expression level of ORP150 in hepatocellular carcinoma, protein expression was determined by Western blot and cell immunochemistry, and messenger RNA(mRNA) expression was detected by quantitative real-time polymerase chain reaction.The effect of ORP150 on apoptosis and invasive potential of hepatocellular carcinoma cells was evaluated using the small interference RNA(siRNA) technique.Both the protein and mRNA expression levels of ORP150 were significantly upregulated in hepatocellular carcinoma cell lines compared with a non-tumor human liver cell line.After transfection with the specific siRNA of ORP150, significantly greater apoptosis of hepatocellular carcinoma cells was induced compared with untransfected cells.However, no significant effect on invasive potential was found.Overexpression of ORP150 was associated with hepatocellular carcinoma, and ORP150 might promote the proliferation of hepatocellular carcinoma cells by inhibiting apoptosis.ORP150 could be a potential therapeutic target for hepatocellular carcinoma.

Focal nodular hyperplasia of the liver: a report of 60 cases / 中国普通外科杂志

Objective To evaluate the diagnosis and treatment of focal nodular!hyperplasia of the liver (FNH). Methods Retrospective analysis was made on 60 FNH cases in terms of clinical findings, images, pathologic examination and surgical treatment. Results Of the 60 FNH patients in our hospital from 1993 to 2003, 41 were male and 19 female. The average age was 37 year′s old. Fifty-five cases had single focus, the other five were of multiple lesion, with tumor diameter 10cm in one. Correct preoperative diagnosis was made in 33 cases (55%). The correct diagnostic rate of BUS, CT and MRI was 33.3%, 58.3% and 72.0%, respectively. All 60 cases underwent operation with an uneventful recovery and without recurrence at follow-up. ConclusionsCT and MRI are mandatory for the diagnosis of FNH. Definite preoperative diagnosis is usually difficult even in cases of typical type of FNH. Surgical resection is the treatment of choice when a patient becomes symptomatic or when malignancy could not be excluded.