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Tumor recurrence and metastasis after liver transplantation (LT) remains one of the most important factors that affect the outcome of LT for hepatocellular carcinoma (HCC). The diagnosis and treatment strategies in the era of precision medicine, including utilizing multi-omics, high-throughput gene sequencing analysis, big data and artificial intelligence to select the biomarkers which can accurately predict the prognosis after LT, evaluating the immune status comprehensively, inducing immune tolerance, providing effective prevention for patients at a high risk of recurrence with sensitive antitumor drugs and attaching importance to individualized treatment for recurrence and metastasis, may further improve the outcome of LT. Combined with experience and review of relevant research articles, the authors elaborate perioperative diagnosis and treatment strategies of LT for HCC, aiming to promote the application of precision medicine in the field of LT.
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Objective:To explore the risk factors influencing the prognosis for patients with hepatocellular carcinoma (HCC) recurrence after liver transplantation and summarize the relevant diagnostic and therapeutic experiences.Methods:The clinicopathological features with diagnosis and treatment plan of 102 recurrent HCC patients fulfilling the Fudan Criteria were compared for survival rate (univariate analysis) and independent prognostic indicators were obtained by Cox multivariate analysis.Results:The 1/3/5-year overall survival rates were 92.2%, 48.6% and 34.6% and the 1/3/5-year survival rates with tumor were 63.2%, 31.0% and 16.7% respectively. Cox regression analysis indicated that patient age, whether tumor can be surgically resected or not and personalized diagnostic & therapeutic plan based upon targeted therapy were independent prognostic factors affecting the overall survival rates and survival rates with tumor.Conclusions:Although HCC recurrence and metastasis after liver transplantation seriously influence patient prognosis, satisfactory outcomes may be obtained for some patients through active, effective and precise managements.
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The focus of clinical research on liver transplantation of hepatocellular carcinoma over past decade is as follows: (1) the appropriate indications, so that the limited liver resources can be used more fairly and reasonably. A number of new indications standards have been proposed and validated. Our country scholar puts forward the standard norms, which could benefit more liver cancer patients from liver transplant. (2) To explore the appropriate immunosuppressive regimen in the control of rejection while preventing and reducing tumor recurrence rate after transplantation. At present, there is not enough clinical trial data to conclude, but for patients with high recurrence risk, it is recommended to minimize the dosage of calmodulin inhibitors and convert them to mTOR inhibitors after liver transplantation. In recent years, the rapid development of cancer precision medicine and immunotherapy technology has provided new opportunities for the study of liver transplantation in liver cancer.
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Objective To explore the influence of interleukin-2 receptor antagonists(IL-2Ra) on the morbidity and prognosis of new onset diabetes after transplantation(NODAT)in liver transplant recipients. Methods Pre-and post-operative clinical data of 879 nondiabetic patients who underwent a liver transplantation between April 2001 and December 2016 were retrospectively studied. All the enrolled patients were divided into IL-2Ra and non-IL-2Ra groups according to the use of IL-2Ra. Transient-NODAT(T-NODAT)and Persistent-NODAT(P-NODAT)were defined according to whether NODAT would be existed continuously. The impacts of IL-2Ra on the cumulative incidence as well as the risk of NODAT and T-NODAT were analyzed through comparison between patients who used IL-2Ra or not. And influence of IL-2Ra on the long-term survival of NODAT patients was further analyzed. Results Among 879 patients,177(32.24%)from the IL-2Ra group(n=549)developed NODAT and 29.38%(n=52)of the NODAT reversed,while 131(39.70%)from the non-IL-2Ra group(n=330)developed NODAT and 26.72%(n=35)of the NODAT reversed. After adjusting for 18 possible confounding factors,the IL-2Ra group had significantly decreased cumulative incidence of NODAT over the non-IL-2Ra group(adjusted P=0.028). COX regression analyses showed that IL-2Ra was a protective factor against NODAT development(HR 0.774;95% CI 0.616-0.973; P=0.028), while the use of IL-2Ra and the reverse of NODAT did not significantly related. In addition, long-term survival of the NODAT patients were far better in the IL-2Ra group(adjusted P=0.001). Conclusion IL-2Ra significantly reduces the risk of NODAT in liver transplant recipients and is beneficial to the long-term survival of NODAT patients.
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Objective To study the reproductive outcome of infertile women suffered from hydrosalpinx treated by laparoscopic salpingostomy or salpingectomy.Methods There were 77 infertile women diagnosed hydrosalpinx by HSG or B ultrasonography and excepted for other infertile factors. Unilateral or bilateral salpingostomy or salpingectomy was performed after hydrosalpinx conifrmed by laparoscopy. Seventy seven patients were followed up for 1 ~ 4 years postoperatively.Results Among 77 cases 39 cases (50.65%) got pregnancy. Thirteen cases (16.88%) conceived spontaneously and 26 cases (33.77%) conceived by IVF-ETin. Thirty ifve cases delivered health babies and 3 cases of pregnancy, 1 cases of early abortion.Conclusion Both laparoscopic surgeries were effective treatment of hydrosalpinx results in infertility. After operation the pregnant rate of those conceived by IVF-ET is higher than spontaneously.
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Objective To appraise and compare protein expression profiles in sera of patients without or with recurrence following liver transplantation for hepatocellular carcinoma (HCC) using SELDI-TOF-MS technique,and establish the diagnostic and predictive model. Methods A total of 76 sera (41 from disease free survival patients and 35 from recurrence individuals) were collected pretransplantation and differentially expressed proteins were identified by SELDI-TOF-MS. The intensity values for each peak were analyzed by Biomarker Wizard Software to screen serum proteome biomarkers related to the recurrence post-transplantation. By using Biomarker Patterns Software, the classification trees were generate. from randomly selected samples (30 fingerprints obtained from each group). The sensitivity and specificity of best decision tree were then chosen for blind test with 16 samples (5 from recurrence individuals and 11 from recurrence-free survival patients). Results There were significant differences only in tumor size and the presence of vascular invasion between recurrence group and recurrence-free survival group (P＜0.05). According to serum protein fingerprints, a total of 368 protein peaks were identified at the mass-to-charge ratio (M/Z) value ranging from 2000 to 300 00. There were 22 significant differential proteins between two groups. Among them, 9 proteins were up-regulated and 13 proteins were down-regulated -espectively in recurrence group. The intensity values of differential proteins were input into BPS for classification tree analysis and the best performing tree could distinguish two groups successfully. As a result of blind assessment for this model,a sensitivity of 80.0 % (4/5) and specificity of 72.7 % (8/11) were obtained. Conclusion Some of differential proteins screened by SELDI-TOF-MS technique in the serum may be correlated with the prognoses of liver transplantation patients with HCC. The decision tree may be useful for the clinical application of formulating the indication for liver transplantation, detecting extrahepatic micrometastasis and setting up the diagnostic and treatment strategies.
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<p><b>OBJECTIVE</b>To investigate the sensitization and mechanism of artificial antigen of chlorogenic acid (CGA-BSA).</p><p><b>METHOD</b>Using intensive immunization to establish allergy animal model on guinea pig and preparing antiserum and tissue for further test. Using HE staining to observe pathology change of lungs, trachea, liver. Using passive mast cell (PMC) degranulation test to observe the immunogenicity of CGA-BSA and using ELISA to detect IgE and histamine in plasma.</p><p><b>RESULT</b>There established allergy animal model on guinea pig, which include a increase cell degranulation by a ratio (63.58 +/- 10.23)% in PMC test, increase of specific antibody IgE and increase of histamine in plasma after provocation by ELISA.</p><p><b>CONCLUSION</b>Allergen CGA-BSA could provoke allergenic response in guinea pig, and the allergic response belongs to type I allergy.</p>
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Animals , Chlorogenic Acid , Allergy and Immunology , Drugs, Chinese Herbal , Guinea Pigs , Histamine Release , Hypersensitivity , Blood , Allergy and Immunology , Immunoglobulin E , Blood , Mast Cells , Allergy and Immunology , Random Allocation , Serum Albumin, Bovine , Allergy and ImmunologyABSTRACT
Objective To construct the recombinant expression vector encoding antisense Tcf fragment for the blockage of abnormal Wnt pathway, and to investigate its effect on the biological behaviors of human hepatocarcinoma cells. Methods Antisense expression vector was transfected into hepatocarcinoma cells SMMC-7721 with GeneJammer. RT-PCR and Western blot were used to detect Tcf expression. Cell proliferation and motility were compared by growth curves and Transwell plate assay. Cell apoptosis was determined by Annexin V and cell cycle was examined by fluorescent staining. Results The stable transfection of antisense Tcf in SMMC-7721 cells significantly reduced Tcf expression at both mRNA and protein levels. Compared with parental and mock-transfected 7721 (7721-vector) cells, antisense Tcf RNA transfected cells 7721-pTas showed much decreased activities of proliferation, migration and invasion in vitro. Furthermore, the apoptosis rate of 7721-pTas cells [(26.34±2.07)%] was significantly higher than that of 7721-vector cells [(6.53±1.02)%] and parental SMMC-7721 cells [(4.33±0.68)%] (P<0.001). The percentages of G0-G1 phase antisense transfected cells were 20.24% and 20.95%, higher than parental SMMC-7721 and 7721-vector cells, and percentages of S phase antisense transfected cells were 11.8% and 11.38%, lower than parental SMMC-7721 and 7721-vector cells, respectively. Conclusions Antisense RNA suppress the growth ability of liver cancer cells by inducing cell apoptosis and impeding the progress of cell cycle, which suggests that selective blockage of abnormal Wnt signal pathway by antisense Tcf RNA may be a potential new gene therapy for liver cancer.
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Objective To investigate the effects of preventive chemotherapy for hepatocellular carcinoma (HCC) exceeding Milan criteria after liver transplantation. Methods The clinical data of 243 patients who had undergone orthotopic liver transplantation for HCC exceeding Milan criteria from April 2001 to July 2007 were retrospectively analyzed. Of all patients, 162 received preventive chemotherapy after transplantation. Results The 1- and 3-year survival rates and disease-free survival rates were not statistically different between patients who had received chemotherapy (78.5%, 63.7% ; 76.8%, 52.5% ) and those without chemotherapy (56.6%, 39.1%; 69.3%, 64.7% ) (X2 = 3.084, 0.444, P > 0.05). Cox regression analysis demonstrated that postoperative chemotherapy was not an independent factor affecting the survival rates of HCC patients without vascular invasion, but an independent factor affecting the survival rates of HCC patients with vascular invasion. Conclusions Early preventive chemotherapy could obviously increase the survival rate and delay the tumor recurrence of patients with HCC exceeding Milan criteria, especially for HCC patients with vascular invasion.
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Objective To investigate the diagnosis and treatment of hepatic metastasis from gastrointestinal stromal turnor(GIST).Methods The clinical data of 16 patients with GIST who had been admitted to our hospitalfrom December 1993 to May 2007 were retrospectively analyzed.Results Of all patients,14 underwent radical resection and 2 underwent palliative operation.Two patients with palliative operation and 3 with radical resection were administered with imatinib postoperatively. All patients were followed up for 3-161 months,and GIST metastasis and invasion was observed in 8 of the 14 patients who received radical resection.Of the 7 patients with hepatic metastasis.3 were treated with hepatic artery chemoembolization,1 was administered with imatinib,2 received reoperation and 1 did not receive any treatment. Reoperation was carried out on 1 patient who had abdominal wall metastasis.The 1-and 3-year survival rates of the 16 patients were 92%and 74%,respectively.Conclusions The recurrence rate of GIST after hepatectomy is high.Complete surgical resection is the best curative treatment for hepatic metastasis from GIST and GIST recurrence.The combination of surgical resection and imatinib administration may help to improve the prognosis of patients with hepatic metastasis from GIST.
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Objective To evaluate salvage liver transplantation(LT)for postoperative tumor recurrence or liver dysfunction in patients of hepatocellular carcinoma(HCC).Methods From April 2001 to March 2006,97 HCC patients with the tumor within Milan Criteria underwent LT as the primary treatment(71 cases)and salvage LT because of after resection tumor recurrence(n=20)or postoperative liver dysfunction(n=6).Perioperative and postoperative parameters and long-term survival were compared between the groups of primary LT and salvage LT.Results The mean age(50.0 years vs.49.7 years),gender,and etiology of liver disease(hepatitis B/C/nonviral)were comparable between the two groups.In the salvage LT group.the mean time between liver resection and LT was 2.50 years.Clinical characteristics such as tumor number(1.37 vs.1.50),operative time(7.92 hours vs.8.56 hours),blood loss (1981.69 ml vs.2626.92 ml)and transfusion(1981.69 ml vs.2626.92 ml)were not statistically different (P＞0.05)between the two groups.The size of largest tumor was significantly different between salvage LT group and the primary LT group(2.81 cm vs.2.05 cm)(t=2.298,P=0.028).By a median follow up of 14.63 months,overall survival after liver transplantation was not different between the 2 groups(X2=0.003.P=0.959).Conclusion In selected patients,liver resection prior to transplantation does not increase the morbidity or impair long.term survival following LT.Therefore.1iver resection prior to transplantation can be integrated with the treatment strategy for HCC.
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OBJECTIVE:To evaluate the long-term toxicity of Ginkgolide B injection on Beagle dogs,and to provide safety evidences for clinical experiment.METHODS: A total of 24 Beagle dogs were equally assigned to receive placebo(control group,n=6) or Ginkgolide B injection at high,medium,and low doses(80,20,and 5 mg?kg-1) by iv gtt for 6 consecutive days per week for up to 90 days.There were 6 Beagle dogs(male: female =1∶1) in each group.All the laboratory indicators were monitored and the recovery of the Beagle dogs was observed.RESULTS: During medication,vomiting was noted in one dog in high dose group,and the clotting time in high and medium dose groups was prolonged obviously.During the recovery stage,one dog in high dose group was strong positive in urinary protein test.No significant drug-associated toxic reactions were noted judging from Beagle dogs' body weight,appetite,temperature,ECG,hematology,blood biochemical analysis,ophthalmology test,marrow test,urine routine test,histopathologic examination etc.CONCLUSION: The non-toxic dose of Ginkgolide B injection for Beagle dogs was 20 mg?kg-1.
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Objective To summarize the interventional management for early hepatic arterial thrombosis(HAT)after liver transplantation.Methods 32 patients suspected of HAT or HAS after liver transplantation in 502 cases from April 2001 to September 2006 were done hepatic arterial angiography.Among them,20 patients were confirmed as HAT immediately through hepatic arterial angiography,and were further treated by transarterial thrombolysis,pereutaneous transluminal angioplasty(PTA)and stent-graft placement. Results HAT was identified in 20 patients(3.98%),occurring in the median 4.5 days(2～19 days)after liver transplantation.The sites of all the thrombosis were found at the anastomotic point of the hepatic artery.5 cases were treated by PTA and 3 cases by stent placement during the transarterial thrombolysis.Coil and stent-graft were used in 2 cases with hepatic arterial anastomostic hemorrhage.Hepatic arterial recanalization was obtained in 20 cases.The period of thrombolysis was 2.5 clays(2-11 days).Conclusions Continuous infusion of urokinase through hepatic artery with catheter,PTA and stent placement are effective modalities for hepatic arterial thrombosis after liver transplantation.(J Intervent Radiol,2007,16:799-802)
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Objective To evaluate clinical effects of combined use of hysteroscopy and laparoscopy in the diagnosis and treatment of infertility with uterine septum,and to analyze the relationship between infertility and uterine septum. Methods Surgery using hysteroscopy combined with laparoscopy was performed in 110 patients with infertility accompanying uterine septum,including primary infertility in 78 patients and secondary infertility in 32 patients.The relative infertility factors and post-operative pregnancy prognoses were analyzed. Results Unexplained infertility accounted for 40% of patients(44/110).As of March 2006,a total of 82 patients were successfully followed.The total post-operative pregnancy rate was 45.1%(37/82),consisting of 46.6% in patients with primary infertility(27/58) and 41.7% in patients with secondary infertility(10/24),without significant difference between the two groups(?~2=0.164,P=0.686).The post-operative pregnancy rates in patients with unexplained infertility and etiologically-clarified infertility were 51.2%(22/43) and 38.5%(15/39),respectively,without significant difference(?~2=1.332,P=0.248).In patients with unexplained infertility,the post-operative pregnancy rate for primary infertility was 56.7%(17/30) and for secondary infertility,38.5%(5/13). Conclusions Combined use of hysteroscopy and laparoscopy for infertility with uterine septum can improve the post-operative pregnancy rate.The presence of uterine septum bears some relationship to the incidence of infertility.
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<p><b>OBJECTIVE</b>To evaluate transcervical removal of foreign bodies (TCRF) and to estimate the effectiveness of its monitoring methods.</p><p><b>METHODS</b>One hundred and thirteen women were identified as having residual intrauterine devices (IUD), residual pregnancy products, unabsorbed strings and broken hooks, which were not removed during routine curettage or IUD removal. All patients were monitored using B ultrasonography while TCRF was performed. Four cases were monitored by laparoscopy simultaneously. One case was monitored by laparoscopic ultrasonography.</p><p><b>RESULTS</b>Foreign bodies of one hundred and nine patients were taken out by TCRF. Uterine bleeding, amenorrhoea, discharge, abdominal pain, micturition and hematuria disappeared postoperatively. Fetal bones embedded into intramural uterin in four cases were not removed completely. Of these four, one became pregnant 4 months later after TCRF and term delivered. One case encountered uterine perforation that was sutured by laparoscopy.</p><p><b>CONCLUSIONS</b>TCRF is safe and efficient. Sufficient cervical canal distension, selection of equipment and methods to be used is important for successful TCRF. As a non-invasive and effective monitoring method, B ultrasonography is the first choice to monitor for TCRF. For patients with high risk factors for uterine perforation, laparoscopic monitoring should be done simultaneously. Laparoscopic ultrasonography monitoring has both the advantages of B ultrasonography and laparoscopy monitoring, but is invasive and expensive.</p>
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Adult , Aged , Female , Humans , Middle Aged , Pregnancy , Foreign Bodies , Diagnostic Imaging , General Surgery , Hysteroscopy , Methods , Intrauterine Devices , Laparoscopy , UltrasonographyABSTRACT
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 10cm 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.