重症急性胰腺炎预防性抗生素治疗的荟萃分析

目的通过对有关文献的荟萃分析,探讨预防性抗生素治疗在重症急性胰腺炎(SAP)中的作用。方法检索1966年到2004年8月期间发表的有关预防性抗生素治疗SAP的作用方面的随机对照临床试验(RCT)。按照人选标准,有6项临床试验纳入本研究,由2名作者各自独立地对入选研究中有关试验设计、研究对象的特征、研究结果等内容进行摘录,并用RevMan4.2软件进行分析。结果在SAP患者中,使用能在胰腺组织中达到有效浓度的广谱抗生素并不能减少胰腺感染(RR=0.77,95% 可信区间为0.48-1.24,P=0.28),也不能减少手术干预(RR=0.84,95%可信区间为0.40-1.74, P=0.64),更不能降低死亡率(RR=0.54,95%可信区间为0.28-1.04,P=0.07),只有胰外感染的发生率有一定的减少(RR=0.52,95%可信区间为0.31-0.88,P=0.01)。结论不建议在SAP患者中不加选择地预防性使用抗生素,但对于CT证实的坏死性胰腺炎,可以考虑抗生素预防性治疗。     

Conventional transarterial chemoembolization vs microsphere embolization in hepatocellular carcinoma: A meta-analysis

AIM:To compare conventional transarterial chemoembolization(c-TACE)with microsphere embolization in hepatocellular carcinoma(HCC).METHODS:We searched Pub Med,Medline,Embase and the Cochrane Library for trials assessing the efficacy and safety of c-TACE in comparison with those of yttrium-90 microsphere or drug-eluting bead embolization from January 2004 to December 2013.Overall survival rate(OSR),tumor response[complete response,partial response(PR),stable disease(SD),progressive disease(PD)],α-fetoprotein(AFP)response,progression rate and complications were compared and analyzed.Pooled ORs with 95%CI were calculated using either the fixed-effects model or random-effects model.All statistical analyses were conducted using the Review Manager(version 5.1.)from the Cochrane collaboration.RESULTS:Thirteen trials were identified,including a total of 1834 patients;1233 were treated with c-TACE,377 underwent yttrium-90 microsphere embolization and 224 underwent drug-eluting bead embolization.The meta-analysis with either the random-effects model or fixed-effects model indicated that microsphere embolization was associated with significantly higher OSRs compared with those of c-TACE(OR1-year=1.38,95%CI1-year:1.05-1.82;OR2-year=2.88,95%CI2-year:1.18-7.05;OR3-year=2.15,95%CI3-year:1.18-3.91).The complete tumor response rates of patients who underwent microspheres embolization were significantly higher than those of patients treated with c-TACE(OR=2.19,95%CI:1.31-3.64).The tumor progression rate after microsphere embolization was markedly lower than that after c-TACE(OR=0.56,95%CI:0.39-0.81).There was no significant difference between microsphere embolization and c-TACE in PR(OR=0.73,95%CI:0.47-1.15),SD(OR=1.07,95%CI:0.79-1.44),PD(OR=0.75,95%CI:0.33-1.68),AFP response(OR=1.38,95%CI:0.64-2.94)and complications(OR=0.68,95%CI:0.46-1.00).CONCLUSION:Our analysis indicated that microsphere embolization was associated with superior survival and treatment response in comparison with c-TACE in the treatment of patients with HCC.     

Randomised controlled trial of lipiodol transarterial chemoembolisation with or without amiodarone for unresectable hepatocellular carcinoma

Background

There is no consensus about the most effective method for transarterial chemoembolisation of hepatocellular carcinoma.

Aim

The aim of this phase II trial was to compare the efficacy and toxicity of lipiodol transarterial chemoembolisation with amiodarone in association with pirarubicin or doxorubicin versus lipiodol transarterial chemoembolisation with anthracycline alone in a control group.

Methods

Patients with unresectable hepatocellular carcinoma and Child-Pugh A/B7 were considered eligible for the trial. transarterial chemoembolisation was repeated every 6 weeks for a maximum of 4 sessions.

Results

Thirteen patients were randomised in the amiodarone group, and 14 were randomised in the control group. The two groups were comparable with respect to their baseline characteristics. The objective response rate according to the EASL criteria was 62% (95% CI 35–88) in the amiodarone group and 50% (95% CI 24–76) in the control group. At 1 and 2 years, survival rates were 77% (95% CI 44–92) and 52% (95% CI 22–75) in the amiodarone group, and 57% (95% CI 28–78) and 40% (95% CI 15–65) in the control group, respectively. There was no difference between the two groups in terms of toxicity.

Conclusions

The results of this study suggest that lipiodol transarterial chemoembolisation with anthracycline and amiodarone was safe but did not increase survival compared with lipiodol transarterial chemoembolisation with anthracycline alone in patients with hepatocellular carcinoma.     

Predictive factors of transarterial chemoembolisation toxicity in unresectable hepatocellular carcinoma

BackgroundTransarterial chemoembolisation (TACE) is an effective treatment for unresectable hepatocellular carcinoma (HCC), but can cause severe toxicity.AimTo identify predictive factors of severe TACE-related toxicity in patients with unresectable HCC.MethodsAll HCC patients who underwent TACE at the Dijon University Hospital between 2008 and 2011 were included in this retrospective study. Severe TACE-related toxicity was defined as the occurrence of any adverse event grade ≥4, or any adverse event that caused a prolongation of hospitalisation of >8 days, or any additional hospitalisation within 1 month after TACE. Factors predicting toxicity were identified using a logistic regression model. The robustness of the final model was confirmed using bootstrapping (500 replications).Results124 patients were included, median age was 67 years and 90% were male; 22 patients (18%) experienced severe TACE-related toxicity. Factors that independently predicted severe TACE-related toxicity in multivariate analysis were total tumour size (OR, 1.15 cm⁻¹; 95%CI, 1.04–1.26; p = 0.01), and high serum AST levels (OR, 1.10 per 10 IU/l; 95%CI, 1.01–1.21; p = 0.04). The results were confirmed by bootstrapping.ConclusionsTotal tumour size and high serum AST levels were predictive factors of severe TACE-related toxicity in this hospital-based series of patients with unresectable HCC.     

Increased extrinsic apoptotic pathway activity in patients with hepatocellular carcinoma following transarterial embolization

AIM:To determine the apoptosis pathway in residualviable hepatocellular carcinoma(HCC) tissues followingtransarterial embolization(TAE) .METHODS:Ten patients with HCC who received sur-gical resection after TAE were enrolled in the study group,and 24 patients with HCC who received surgical resection only served as the control group. In thestudy group,we measured the changes in tumor sizeand α fetoprotein(AFP) levels after TAE. All tissuesamples were taken from the residual tumors. The ex-pression of various ...     

Impact of pre-operative transarterial embolization on the treatment of hepatocellular carcinoma with liver transplantation

AIM: To determine the effectiveness of pre-liver transplant (LT) transarterial embolization (TAE) in treating hepatocellular carcinoma (HCC) and the patient categories, which are likely to have a good outcome after LT. METHODS: Twenty-nine patients with hepatitis-related cirrhosis and unresectable HCC after LT were studied over a 7-year period. The patients were divided into two groups: group A patients (19/29) received pre-LT TAE, whereas group B (10/29) underwent LT without prior TAE. According to Milan criteria, group A patients were further subdivided into: group A1(12/19) who met the criteria, and group A2 (7/19) who did not. Patient survivals were compared. RESULTS: In the explanted liver, CT images correlated well with pathological specimens showing that TAE induced massive tumor necrosis (>85%) in 63.1% of patients in group A and all 7 patients in group A2 exhibited tumor downgrading that met Milan criteria. The overall 5-year actuarial survival rate was 80.6%. The TAE group had a better survival (84% at 5 years) than the non-TAE (75% at 4 years). The 3-year survival of group A2 (83%) was also higher than that of group A1(79%). Tumor necrosis >85% was associated with excellent survival of 100% at 3 years, which was significantly better than the others who showed <85% tumor necrosis (57.1% at 3 years) or who did not have TAE (75% at 3 years). CONCLUSION: TAE is an effective treatment for HCC before LT. Excellent long-term survival was achieved in patients that did not fit Milan criteria. Our results broadened and redefined the selection policy for LT among patients with HCC. Meticulous pre-LT TAE helps in further reducing the rate of dropout from waiting lists and should be considered for patients with advanced HCC.     

Hepatocellular carcinoma after locoregional therapy: Magnetic resonance imaging findings in falsely negative exams

AIM: To elucidate causes for false negative magnetic resonance imaging (MRI) exams by identifying imaging characteristics that predict viable hepatocellular carcinoma (HCC) in lesions previously treated with locoregional therapy when obvious findings of recurrence are absent. METHODS: This retrospective institutional review board-approved and Health Insurance Portability and Accountability Act-compliant study included patients who underwent liver transplantation at our center between 1/1/2000 and 12/31/2012 after being treated for HCC with locoregional therapy. All selected patients had a contrast-enhanced MRI after locoregional therapy within 90 d of transplant that was prospectively interpreted as without evidence of residual or recurrent tumor. Retrospectively, 2 radiologists, blinded to clinical and pathological data, independently reviewed the pre-transplant MRIs for 7 imaging features. Liver explant histopathology provided the reference standard, with clinically significant tumor defined as viable tumor ≥ 1.0 cm in maximum dimension. Fisher’s exact test was first performed to identify significant imaging features. RESULTS: Inclusion criteria selected for 42 patients with 65 treated lesions. Fourteen of 42 patients (33%) and 16 of 65 treated lesions (25%) had clinically significant viable tumor on explant histology. None of the 7 imaging findings examined could reliably and reproducibly determine which treated lesion had viable tumor when the exam had been prospectively read as without evidence of viable HCC. CONCLUSION: After locoregional therapy some treated lesions that do not demonstrate any MRI evidence of HCC will contain viable tumor. As such even patients with a negative MRI following treatment should receive regular short-term imaging surveillance because some have occult viable tumor. The possibility of occult tumor should be a consideration when contemplating any action which might delay liver transplant.     

A prediction model for liver abscess developing after transarterial chemoembolization in patients with hepatocellular carcinoma

BackgroundLiver abscess is a rare but potentially fatal complication of transarterial chemoembolization. Other than for biliary abnormalities, risk factors for liver abscess formation after transarterial chemoembolization have rarely been discussed.AimsTo identify other risk factors of liver abscess after transarterial chemoembolization in patients with hepatocellular carcinoma.MethodsData for 5299 patients with hepatocellular carcinoma who underwent transarterial chemoembolization from July 1999 to December 2009 were retrospectively reviewed. 72 patients who experienced liver abscess after transarterial chemoembolization were enrolled as a case group, which was compared with a randomly selected control group (n = 1009) of patients who did not develop liver abscess after transarterial chemoembolization.ResultsPneumobilia, type 2 biliary abnormality, type 1 biliary abnormality, diabetes mellitus, tumour number (≥3), tumour size (≥3 cm), and tumour necrosis on the pre-transarterial chemoembolization computed tomography, and gelfoam embolization and vessel injury during transarterial chemoembolization were all significant predisposing factors for liver abscess after transarterial chemoembolization. A prediction model for postembolization liver abscess was developed from these risk factors.ConclusionThe group of patients with risk scores greater than 71 showed a significantly increased risk of liver abscess after transarterial chemoembolization. These high-risk patients should be monitored carefully after transarterial chemoembolization.     

Novel biomarkers GEP/ABCB5 regulate response to adjuvant transarterial chemoembolization after curative hepatectomy for hepatocellular carcinoma

Background: Transarterial chemoembolization(TACE) is the most commonly used adjuvant therapy for hepatocellular carcinoma(HCC) after curative resection. Responses to TACE are variable due to tumor and patient heterogeneity. We had previously demonstrated that expression of Granulin-epithelin precursor(GEP) and ATP-dependent binding cassette(ABC)B5 in liver cancer stem cells was associated with chemoresistance. The present study aimed to evaluate the association between GEP/ABCB5 expression and response to adjuvant TACE after curative resection for HCC. Methods: Patients received adjuvant TACE after curative resection for HCC and patients received curative resection alone were identified from a prospectively collected database. Clinical samples were retrieved for biomarker analysis. Patients were categorized into 3 risk groups according to their GEP/ABCB5 status for survival analysis: low(GEP-/ABCB5-), intermediate(either GEP +/ABCB5-or GEP-/ABCB5 +) and high(GEP +/ABCB5 +). Early recurrence(recurrence within 2 years after resection) and disease-free survival were analyzed. Results: Clinical samples from 44 patients who had followed-up for more than 2 years were retrieved for further biomarker analysis. Among them, 18 received adjuvant TACE and 26 received surgery alone. Patients with adjuvant TACE in the intermediate risk group was associated with significantly better overall survival and 2-year disease-free survival than those who had surgery alone( P = 0.036 and P = 0.011, respectively). Adjuvant TACE did not offer any significant differences in the early recurrence rate, 2-year disease-free survival and overall survival for patients in low and high risk groups. Conclusions: Adjuvant TACE can only provide survival benefits for patients in the intermediate risk group(either GEP +/ABCB5-or GEP-/ABCB5 +). A larger clinical study is warranted to confirm its role in patient selection for adjuvant TACE.     

Current systemic treatment of hepatocellular carcinoma: A review of the literature

Hepatocellular carcinoma (HCC) is the fifth most common form of human cancer worldwide and the third most common cause of cancer-related deaths. The strategies of various treatments for HCC depend on the stage of tumor, the status of patient’s performance and the reserved hepatic function. The Barcelona Clinic Liver Cancer (BCLC) staging system is currently used most for patients with HCC. For example, for patients with BCLC stage 0 (very early stage) and stage A (early stage) HCC, the curable treatment modalities, including resection, transplantation and radiofrequency ablation, are taken into consideration. If the patients are in BCLC stage B (intermediate stage) and stage C (advanced stage) HCC, they may need the palliative transarterial chemoembolization and even the target medication of sorafenib. In addition, symptomatic treatment is always recommended for patients with BCLC stage D (end stage) HCC. In this review, we will attempt to summarize the historical perspective and the current developments of systemic therapies in BCLC stage B and C in HCC.     

原发性肝癌的非手术治疗

原发性肝癌（下简称肝癌）主要是肝细胞癌，少数是胆管细胞癌。我国是肝癌高发地区，其恶性程度高，进展快，治疗棘手，预后差。外科手术切除或肝移植是最有效的治疗，但绝大多数病例属于中晚期或有严重的肝硬化，而不适合外科手术治疗^[1]，因而非手术治疗适用于大多数病例或与外科手术相结合提高治疗效果^[1,2]。     

Outcome of transarterial chemoembolization in patients with inoperable hepatocellular carcinoma eligible for radiofrequency ablation

AIM: To evaluate the outcome of transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (HCC)<5 cm in diameter eligible for radiofrequency ablation (RFA). METHODS: The treatment-related mortality, morbidity, long-term survival, and prognostic factors of HCC patients who had TACE and fulfilled the present inclusion criteria for RFA were evaluated. RESULTS: Of the 748 patients treated with TACE between January 1990 and December 2002,114 patients were also eligible for RFA. The treatment-related mortality and morbidity were 1% and 19%, respectively. Survival at 1, 3, and 5 years was 80%, 43%, and 23%, respectively. Older age and a high albumin level were associated with a better survival, whereas a high a-fetoprotein level (AFP) and the size of the largest tumor >3 cm in diameter were adverse prognostic factors in multivariate analysis. CONCLUSION: The morbidity, mortality, and survival data after TACE for small HCCs eligible for RFA are comparable to those reported after RFA in the literature. Our data suggest the need for a randomized comparison of the two treatment modalities for small HCCs.     

Transarterial embolization ablation of hepatocellular carcinoma with a lipiodol-ethanol mixture

AIM: To determine the safety and effectiveness of transarterial embolization ablation (TEA) of hepatocellular carcinoma (HCC) with a lipiodol-ethanol mixture. METHODS: Between January 1 and December 31, 2009, 15 patients with HCC (13 men/two women, aged 38-75 years) accepted TEA treatment and were enrolled in this study, including five newly diagnosed patients and 10 with refractory disease. Two months after TEA, angiography and contrast computed tomography (CT) were performed, and responses were assessed using a modified version of Response Evaluation Criteria in Solid Tumors (RECIST version 1.1). The follow-up period was to June 30, 2010. RESULTS: Every new case was treated once. Angiography was performed immediately after TEA, and showed that the tumor-feeding vessels were completely embolized and that lipiodol was densely deposited inside tumors. Two months after treatment, contrast CT showed no enhanced lesions. Alpha fetoprotein levels returned to normal in four patients and markedly decreased in another. mean ± SD survival after treatment was 10.8 ± 4.5 mo. All five patients survived during the follow-up period. Ten patients with refractory disease were treated a total of 14 times. Angiography immediately after TEA showed that blood flow to the tumors was obviously decreased in all cases, and contrast CT showed obvious depositions of lipiodol. Two months after treatment, the tumors had shrunk (6/10) or were stable (3/10). One had progressed after 2 mo and died of tumor rupture 3 mo after TEA. mean ± SD survival after treatment was 8.6 ± 4.3 mo; two patients survived during the follow-up period. Adverse effects included reversible hepatic decompensation, upper abdominal pain, and fever. CONCLUSION: TEA is an effective therapy for patients with HCC and might be more effective than transcather arterial chemoembolization for treating refractory disease.     

经肝动脉化疗栓塞后联合索拉非尼治疗肝癌患者临床观察

目的探讨索拉非尼联合经肝动脉化疗栓塞术（TACE）治疗肝癌患者的效果。方法选取142例肝癌患者,其中57例接受TACE治疗,47例接受索拉非尼治疗,38例接受索拉非尼联合TACE治疗。在治疗后12 w,评估治疗效果、总生存期（OS）和疾病进展时间（TTP）。结果联合治疗组有效率为26.32%,显著高于TACE组的17.54%或索拉非尼组的19.15%（P<0.05）;联合治疗组疾病控制率为71.05%,显著高于TACE组的57.89%或索拉非尼组的53.19%（P<0.01）;联合治疗组患者OS为8.6 m,显著高于索拉非尼组的6.2 m或TACE组的7.3 m（P<0.05）;联合治疗组TTP为6.7 m,显著高于索拉非尼组的5.1m或TACE组的 5.6 m（P<0.01）。结论索拉非尼联合TACE治疗肝癌患者具有较好的临床效果。     

Transarterial chemoembolization in patients with hepatocellular carcinoma: predictors of survival

BACKGROUND:

Transarterial chemoembolization (TACE) is the mainstay of management for patients with hepatocellular carcinoma who are not suitable for curative treatments.

OBJECTIVE:

To determine factors associated with mortality after the first TACE procedure.

METHODS:

From January 2004 to May 2008, 60 patients underwent TACE as treatment for hepatocellular carcinoma. Clinical and biochemical parameters before TACE, and response after TACE, were evaluated with conventional classifications (WHO, Response Evaluation Criteria in Solid Tumors [RECIST], and European Association for the Study of the Liver [EASL] criteria) and with one-, two- and three-dimensional assessment.

RESULTS:

Overall median survival after the first TACE procedure was 17.1±3.4 months. According to Cox regression analysis, having an alpha-fetoprotein level of greater than 200 ng/mL (HR 2.35 [P=0.02]) and a Model for End-stage Liver Disease (MELD) score of greater than 10 (HR 4.19 [P=0.001]) were associated with higher risk of mortality; whereas reduction in tumour size measured in one dimension (HR 0.96 [P=0.005]), two dimensions (HR 0.98 [P=0.004]) and three dimensions (HR 0.98 [P=0.001]) was associated with lower risk of mortality. Moreover, reduction in tumour size by 3% or more assessed in one, two or three dimensions was associated with lower risk of mortality (HR 0.48 [P=0.04]; HR 0.36 [P=0.01]; HR 0.31 [P=0.003], respectively). The three conventional classifications were not useful for predicting mortality (WHO: HR 1.07 [P=0.9]; RECIST: HR 0.94 [P=0.9]; EASL: HR 0.94 [P=0.9]).

CONCLUSIONS:

Having an alpha-fetoprotein level of greater than 200 ng/mL and a MELD score of greater than 10 before undergoing TACE was associated with a greater risk of mortality. Conventional classifications of response were not useful for predicting mortality. Reduction in tumour size after the first TACE procedure was associated with better survival, primarily if patients had more than a 3% reduction in tumour size assessed by three-dimensional measurement.