Transcatheter arterial chemoembolization or chemoinfusion for unresectable intrahepatic cholangiocarcinoma: clinical efficacy and factors influencing outcomes

BACKGROUND.

The role of transcatheter arterial chemoembolization (TACE) or transcatheter arterial chemoinfusion (TACI) for unresectable intrahepatic cholangiocarcinoma (ICC) has recently been questioned. The aim of the study was to evaluate the clinical efficacy of TACE or TACI in patients with unresectable ICC and to identify prognostic factors associated with clinical success.

METHODS.

From 1997 to 2007, 49 patients with unresectable ICC were treated with TACE (n = 124) or transcatheter arterial chemoinfusion (TACI) (n = 96). Tumor response was evaluated based on computed tomography scans obtained 1 month to 3 months after TACE or TACI. Factors associated with clinical success were evaluated using multivariate logistic regression analysis. Factors associated with the survival period were evaluated using multivariate Cox regression analysis.

RESULTS.

After treatment, 27 (55%) of the patients showed radiographic response. Multivariate analysis confirmed that tumor vascularity (odds ratio [OR], 31.2; P = .002) was the only independent factor associated with radiographic response. The median and mean survival periods in our study patients were 12 and 24 months. Multivariate Cox regression analyses showed that tumor size (OR, 2.64; P = .048), tumor vascularity (OR, 13.5; P < .001), and the Child‐Pugh class (OR, 3.65; P = .014) were the independent factors associated with the length of the survival period.

CONCLUSIONS.

Hepatic intra‐arterial chemotherapy is well tolerated and may be effective to prolong survival of patients with unresectable ICC. Tumor vascularity is significantly associated with radiographic response. Large tumor size, tumor hypovascularity, and Child‐Pugh class B were poor prognostic factors for determining the patient survival period. Cancer 2008. © 2008 American Cancer Society.     

Localized unresectable neuroblastoma: results of treatment based on clinical prognostic factors.

BACKGROUND: We previously reported that stage 3 neuroblastoma comprises (i) a low-risk group including all infants (age 0-11 months) as well as older children with non-abdominal primaries, and (ii) a high-risk group made up of children >1 year of age with abdominal primaries. Aggressive chemotherapy was effective only in the latter group. PATIENTS AND TREATMENT: On this basis, in 1990 we designed a new protocol by which all low-risk patients received standard-dose chemotherapy, while the high-risk ones received very aggressive chemotherapy. RESULTS: Between November 1990 and December 1997 a total of 95 eligible and evaluable children were enrolled: 47 were low-risk (35 infants and 12>1 year of age at diagnosis and having non-abdominal primaries), and 48 were high-risk (being >1 year of age and having abdominal primaries). Of the 47 low-risk patients, five relapsed and four subsequently died. The 5-year overall survival (OS) was 91%. Of the 48 patients in the high-risk group, 22 relapsed or progressed, 18 of whom died from their disease and two from toxicity, and one was lost to follow-up. The 5-year OS was 60%. Univariate analysis showed that age, site of primary, risk-group, urine vanillylmandelic excretion, plasma levels of lactate dehydrogenase, ferritin and neurone-specific enolase, and MYCN status correlated with outcome. However, multivariate analysis showed that only MYCN status retained prognostic value. CONCLUSIONS: In low-risk stage 3 neuroblastoma, standard-dose chemotherapy is associated with an excellent chance of being cured. Aggressive chemotherapy is effective for high-risk patients, but results are still unsatisfactory. MYCN gene amplification is a prognostic indicator for most, but not all, treatment failures.     

可切除肝门部胆管癌患者临床病理特征及预后影响因素分析

目的:探讨可切除肝门部胆管癌（hilar cholangiocarcinoma,HC）患者术前血清CEA、CA19-9水平与临床病理因素的相关性,并进一步分析上述各因素与HC患者行根治术后预后的相关性。方法:回顾性分析2012年1月至2018年1月中国医科大学附属盛京医院收治的109例行根治性切除的HC患者的临床病理资料,研究术前血清CEA、CA19-9水平与各临床病理特征的相关性,并进一步分析上述各因素与HC患者行根治性切除术后预后的相关性。结果:术前血清CEA水平与HC各临床病理特征无关（P＞0.05）。术前黄疸越重,血清CA19-9水平越高（P＜0.05）。肿瘤侵犯血管的HC患者,术前血清CA19-9水平较高（P＜0.05）。HC患者TNM分期越晚,术前血清CA19-9水平越高（P＜0.05）。门静脉侵犯、淋巴结转移、TNM分期以及术前血清CA19-9水平是影响HC患者术后1年生存率的危险因素（P＜0.05）,其中淋巴结转移、门静脉侵犯、CA19-9是影响患者术后1年生存率的独立危险因素（P＜0.05）。结论:可切除HC患者术前血清CA19-9水平与临床分期及血管侵犯情况存在一定相关性;早期 HC患者行根治性切除术后预后较好,提高HC早期诊断率有助于进一步改善HC患者的生存预后;结合术前血清CA19-9水平、门静脉侵犯及淋巴结转移等多种因素可预测HC患者行根治性切除术后的生存率。     

伽马刀治疗胆管癌预后因素分析

目的：分析影响伽马刀治疗胆管癌的预后因素。方法：回顾性收集2005年1月至2010年12月期间在北京武警总医院接受伽马刀治疗的63例胆管癌患者临床资料,采用 Kaplan －Meirer 法进行单因素分析, Cox 回归模型进行多因素分析。结果：单因素分析结果显示：患者放疗前 CA19－9水平、淋巴结转移、血管侵犯、肿瘤体积、TNM分期为胆管癌γ－刀治疗后影响预后的相关因素。多因素分析结果显示：淋巴结转移、血管受侵、TNM分期为胆管癌γ－刀治疗后影响预后的独立危险因素。结论：患者放疗前 CA19－9≥156U ／ml、淋巴结转移、血管侵犯、GTV≥98cc、TNM分期级别越高往往提示预后不佳。其中,淋巴结转移、血管侵犯、TNM分期为胆管癌γ－刀治疗后影响预后的独立因素。     

手术切除的肝门部胆管癌的临床特点及预后因素分析

目的 探讨经手术治疗的肝门部胆管癌患者的临床特点及与预后相关的因素。方法 回顾性分析58例行手术治疗的肝门部胆管癌患者的临床资料,应用Kaplan-Meier法计算生存率,对可能影响患者预后的因素分别进行单因素分析(Log-rank检验),应用Cox比例风险模型进行多因素统计分析。结果 58例肝门部胆管癌患者的中位生存时间为22.00个月,1年、3年、5年生存率分别为76%、40%和21%。单因素分析表明术前血清白蛋白(P=0.002)、术中出血量(P=0.039)、手术方式(P=0.006)、分化程度(P=0.001)、是否侵及门静脉(P=0.014)、手术切缘有无癌细胞(P=0.020)对患者的术后生存时间有显著性影响。多因素分析结果显示手术方式(P=0.022)、肿瘤分化程度(P=0.020)是影响患者生存的独立预后因素。结论 术前血清白蛋白低于35g/L、术中出血量大于＞500mL、肿瘤低分化、门静脉浸润、根治性切除(R₀)、手术切缘癌细胞阳性是影响肝门部胆管癌患者预后的危险因素。     

The effect of trans arterial chemoembolization in the management of intrahepatic cholangiocarcinoma. A systematic review and meta-analysis

BackgroundA comprehensive re-evaluation on the role of trans-arterial chemoembolization (TACE) in patients with intrahepatic cholangiocarcinoma.MethodsA thorough database searching was performed in PubMed, EMBASE, and the Cochrane Library. Eligible studies were restricted to comparative studies between TACE and non-TACE cohorts. RevMan5.3 software and Stata 13.0 software were used for statistical analyses. The primary endpoint of our study was long-term survival.ResultsA total of 11 studies with 2036 patients were finally identified. Pooled results revealed that patients receiving TACE had a significantly better overall survival (OS) versus those without TACE (P < 0.05). Subgroup analyses were performed according to different types of TACE. Prophylactic post-surgical TACE (PPTACE) was associated with a significantly better OS versus those without PPTACE (P < 0.05). Palliative TACE (PTACE) also achieved a significantly better OS compared with those with supportive treatment (ST) only (P < 0.00001). However, TACE had no impact on disease-free survival (P = 0.87) and was less effective than surgical resection (P = 0.003).ConclusionPPTACE has a remarkable impact on OS versus those with surgical resections only and should be regularly performed. Regarding patients with unresectable disease, apart from conventional ST, adjuvant PTACE is also recommended. Upcoming prospective randomized controlled trials are warranted for further validation.     

Postoperative adjuvant transcatheter arterial chemoembolisation improves survival of intrahepatic cholangiocarcinoma patients with poor prognostic factors: Results of a large monocentric series

Background

The prognosis of patients with intrahepatic cholangiocarcinoma (ICC) is currently unsatisfactory. The aims of this study were to identify prognostic factors after curative ICC resection, and to evaluate the effects of postoperative transcatheter arterial chemoembolisation (TACE).

Methods

A retrospective analysis was conducted of 114 ICC patients who underwent curative resection from January 2005 to December 2006. Relationships between survival and clinicopathological factors were evaluated using univariate and multivariate analyses. The benefits of adjuvant TACE were investigated separately.

Results

The cumulative 1-, 3-, and 5-year survival rates were 63%, 26%, and 15%, respectively. Multivariate analysis revealed that tumour size ≥5 cm (hazard ratio [HR] 1.875, 95% CI 1.139–3.088, P = 0.013) and advanced TNM stage (stage III or IV) (HR 1.681, 95% CI 1.035–2.732, P = 0.036) were independently associated with poor prognosis. Fifty-seven patients underwent adjuvant TACE. In patients with poor prognostic factors, TACE improved the survival rate (P < 0.001). However, in patients without poor prognostic factors, TACE did not significantly change the survival rate (P = 0.724).

Conclusions

Postoperative adjuvant TACE can prolong survival in ICC patients with tumour size ≥5 cm or advanced TNM stage.     

Prognosis and prognostic factors of patients with mesothelioma: a population-based study

Background:

It is important to regularly update survival estimates of patients with malignant mesothelioma as prognosis may vary according to epidemiologic factors and diagnostic and therapeutic management.

Methods:

We assessed overall (baseline) survival as well as related prognostic variables in a large cohort of 1353 patients with a confirmed diagnosis of malignant mesothelioma between 2005 and 2008.

Results:

About 50% of the patients were 70 years or older at diagnosis and the median latency time since start of asbestos exposure was 49 years. One year after diagnosis, 47% of the patients were alive, 20% after 2 years and 15% after 3 years. Prognostic variables independently associated with worse survival were: older age (HR=1.04 per year 95% CI (1.03–1.06)), sarcomatoid subtype (HR=2.45 95% CI (2.06–2.90)) and non-pleural localisation (HR=1.67 95% CI (1.26–2.22)).

Conclusion:

Survival of patients with malignant mesothelioma is still limited and depends highly on patient age, mesothelioma subtype and localisation. In addition, a substantial part of the patients had a long latency time between asbestos exposure and diagnosis.     

Results of combined treatment with transcatheter hepatic arterial chemoembolization and whole-liver irradiation with the moving strip technique in unresectable hepatocellular carcinoma

Background. The best method for the treatment of primary hepatocellular carcinoma (HCC) is surgical resection. However, the operability/resectibility is low because of the advanced stage of the lesion or associated liver disease when diagnosed. The purpose of this study was to evaluate the efficacy of combination treatment with transcatheter hepatic arterial chemoembolization (THAC) and whole-liver irradiation with the moving strip technique for inoperable/unresectable advanced primary HCC. Methods. From January 1998 to January 1990, 60 patients with histologically proven inoperable/unresectable advanced primary HCC were randomly allocated by the envelope method, prospectively, into three groups. Group 1 consisted of 20 patients treated with whole-liver irradiation with the moving strip technique; group 2 consisted of 20 patients treated with transcatheter hepatic arterial chemoembolization (THAC); and group 3 consisted of 20 patients treated with a combination of these two methods. Results. All the patients were followed over a period of 5 years. The 3-month survival rates of groups 1, 2, and 3 were 80%, 85%, and 95% respectively. The 6-month survivals in groups 1, 2, and 3 were 20%, 60%, and 70% respectively. The 12-month survivals in groups 1, 2, and 3 were 0, 25%, and 40%, respectively. The 2-year survivals in groups 1, 2, and 3 were 0, 15%, and 25%, respectively. The 3-year survivals in groups 1, 2, and 3 were 0, 5%, and 15%, respectively. The 5-year survivals in groups 1, 2, and 3 were 0, 0, and 10%, respectively. Conclusion. Combination treatment with THAC and whole-liver irradiation with the moving strip technique is feasible and safe and could be a promising modality for inoperable/unresectable advanced primary HCC. Received: March 9, 1999 / Accepted: August 29, 2000     

肝内胆管细胞癌患者的预后影响因素分析

目的 分析影响肝内胆管细胞癌(ICC)患者预后的相关临床病理因素,并对ICC的外科治疗方式进行探讨.方法 回顾性分析43例经病理证实为ICC患者的临床病理资料.43例[CC患者中,40例行肝切除术,2例在剖腹探查时行无水酒精注射,1例仅行剖腹探查.采用单因素和Cox回归模型对可能影响ICC患者术后生存的因素进行分析.结果 全组43例患者的1、3和5年生存率分别为64.4%、30.9%和25.8%.40例行肝切除患者的术后1、3和5年生存率分别为74.7%、33.3%和27.8%.单因素分析结果显示,肿瘤直径、有无淋巴结转移、癌胚抗原(CEA)水平和TNM分期与ICC患者的术后生存显著相关(均P＜0.05).Cox多因素分析结果显示,肿瘤直径和有无淋巴结转移是影响ICC患者术后生存的独立因素(均P＜0.05).结论 肿瘤直径和有无淋巴结转移是影响ICC患者术后生存的独立因素,CEA水平和TNM分期是影响ICC患者术后生存的重要因素.对ICC患者应选择行根治性肝切除术.     

Papillary thyroid microcarcinoma: prognostic factors and treatment

BACKGROUND AND OBJECTIVES: Within the group of patients with papillary thyroid microcarcinoma (PTMC), the prognostic factors have not been well defined and the optimal treatment has not been proved. The aim of this study was to find out the factors associated with the tumor recurrence in the patients with PTMC. METHODS: A total of 228 patients with PTMC (189 females, 39 males; age 14-85 years, median 46 years) were treated at our Institute between 1975 and 2006. The data on patients' gender, age, extent of disease, pathomorphological characteristics, therapy, locoregional control, disease-free survival and disease-specific survival were collected. Statistical correlation between possible prognostic factors and the duration of disease-free interval was analyzed by univariate and Cox's multivariate survival analysis. RESULTS: The tumor diameter ranged from 0.1 to 10 mm (mean 6.1 mm). The median length of observation was 84 months (range 1-385). During the follow-up period, the recurrence was diagnosed in 7 patients (6 locoregional and 1 distant). Multivariate analysis showed that tumor size and lymph node metastases were independent prognostic factors for disease-free interval. CONCLUSIONS: Longer disease-free interval was found in the patients with a tumor diameter < or =6 mm and without lymph-node metastases.     

术前预后营养指数在肝内胆管癌根治性切除术后的预后预测价值

目的:探讨术前预后营养指数（prognostic nutritional index,PNI）在肝内胆管癌根治性切除术后的预后预测价值。方法:回顾性分析2012年1月至2018年12月于我院普通外科因肝内胆管癌行根治性切除术的107例患者的临床病理资料,分析PNI与患者临床病理特征、预后预测价值及其与预后的关系。结果:术前低PNI组与高PNI组患者的临床病理特征分析显示:低PNI组患者中CEA>5.0 ng/mL、CA19-9>39.0 U/mL、Child-Pugh肝功分级呈B级、肿瘤大小>5 cm、T分期呈T3及T4期、N1期比例明显高于高PNI组患者（P＜0.05）。单因素分析显示,PNI是影响患者预后的危险因素（P＜0.05）。多因素分析显示,PNI是影响患者预后的独立危险因素(P＜0.05)。时间依赖的ROC曲线显示:PNI在预测患者术后的1年、3年及5年总体生存期的AUC分别为67.93%、70.44%及68.32%。对独立危险因素分层分析发现:CEA≤5.0 ng/mL、CA19-9≤39.0 U/mL、CA19-9>39.0 U/mL及N0患者中低PNI组和高PNI组总体生存时间具有统计学差异（P＜0.05）。结论:术前PNI是肝内胆管癌根治性切除术后的独立危险因素,可用于患者预后预测。术前PNI对于CEA≤5.0 ng/mL、CA19-9≤39.0 U/mL、CA19-9>39.0 U/mL及N0者具有更好的预后预测价值。     

食管癌预后相关因素的研究

食管癌是一种常见恶性肿瘤,我国更是高发地区之一,其预后很差,5年总的生存率低于20％。因目前对食管癌的预后因素尚不清楚,本文尝试从病理类型、TNM分期、治疗模式的选择、分子标记物和患者一般状况5个方面探讨食管癌的预后因素及其对食管癌预后的影响。     

滤泡型淋巴瘤患者临床特征及预后因素分析

目的:分析滤泡型淋巴瘤（follicular lymphoma,FL）患者的临床特征及预后因素。方法:对2006年至2016年115例经我院病理科确诊为FL患者进行回顾性病理及临床特征分析,其中62例住院诊治的患者中,30例接受含有利妥昔单抗方案的治疗,22例患者进行普通化疗,10例患者未行任何治疗,并随访观察。结果:62例患者中,利妥昔单抗联合化疗组和单用化疗组,2年OS率均为100%,5年OS率分别为90%和70%,OS间无显著性差异（P=0.332 5）。2年PFS率分别为94%和84%,5年PFS率分别为84%和49%,PFS间有显著性差异（P=0.025 3）。FLIPI-2预后分析,中危组中利妥昔单抗联合化疗与单用化疗组间2年PFS分别为100%、80%,有显著性差异（P=0.021 9）,低危组中利妥昔单抗联合化疗与单用化疗组间2年PFS分别为100%、95%,高危组中利妥昔单抗联合化疗与单用化疗组间2年PFS分别为92%、76%,低危组和高危组中利妥昔单抗联合化疗与单用化疗组相比PFS均无显著性差异。CD10表达阳性组的总反应率（37.14%）明显高于阴性组（22.86%）。结论:FL好发于60岁以下男性,结外病变少见,预后分层多为低危组。规律利妥昔单抗联合化疗可以进一步提高缓解率,延长生存期。     

Weekly high-dose cisplatin is a feasible treatment option: analysis on prognostic factors for toxicity in 400 patients

In the present study we describe the toxicity of weekly high-dose (70-85 mg x m(-2)) cisplatin in 400 patients (203 men, 197 women; median age 54 years) with advanced solid tumours treated in the period 1990-2001 who took part in phase I/II trials, investigating the feasibility and efficacy of weekly cisplatin alone, or in combination with paclitaxel or etoposide. Cisplatin was administered in 250 ml NaCl 3% over 3 h, for six intended administrations. The mean number of administrations was 5.3 (range, 1-6 administrations). Reasons not to complete six cycles were disease progression (7.5%), haematological toxicity (9%), nephrotoxicity (7%), ototoxicity (2.5%), neurotoxicity (1%), gastrointestinal toxicity (1%), cardiovascular complications (0.5%) or a combination of reasons including noncompliance and patient's request (5.5%). Logistic regression analysis was used to evaluate baseline parameters for prognostic value regarding toxicity. Leukopenia correlated with etoposide cotreatment, and thrombocytopenia with cisplatin dose and prior (platinum-based) chemotherapy. Risk factors for nephrotoxicity were older age, female gender, smoking, hypoalbuminaemia and paclitaxel coadministration. Neurotoxicity >grade 1 (11% of patients) was associated with prior chemotherapy and paclitaxel coadministration. Symptomatic hearing loss occurred in 15% with anaemia as the predisposing factor. We conclude that weekly high-dose cisplatin administered in hypertonic saline is a feasible treatment regimen.     

Phase 2 trial of concurrent bevacizumab and transhepatic arterial chemoembolization in patients with unresectable hepatocellular carcinoma

BACKGROUND:

Vascular endothelial growth factor is up‐regulated in hepatocellular carcinoma (HCC) and is further up‐regulated after transhepatic arterial chemoembolization. The authors of this report conducted a phase 2 trial to evaluate the safety and efficacy of bevacizumab combined with chemoembolization in patients with unresectable HCC.

METHODS:

Patients who had an Eastern Cooperative Oncology Group performance of status 0 to 2, a Child‐Pugh score of A or B, and Barcelona Clinic Liver Cancer stage B or C HCC were eligible. Treatment consisted of bevacizumab every 2 weeks and chemoembolization during the third week of a 6‐week cycle for up to 3 cycles over 6 months. The primary endpoints were safety and efficacy.

RESULTS:

Twenty‐five patients received chemoembolization and bevacizumab. The most common grade 3 and 4 events after the first treatment cycle were leukocytopenia (12%), fatigue (12%), and hyponatremia (12%). Serious toxicities that had a known association with bevacizumab were observed in 4 patients. Thirty‐day mortality was 0%. The median time to tumor progression for the targeted lesions was not reached, and overall survival was 10.8 months. The objective response rate was 60% using enhancement response evaluation criteria, and the disease control rate was 100%.

CONCLUSIONS:

Concurrent treatment with bevacizumab and chemoembolization was safe in carefully selected patients and demonstrated antitumor activity in patients with unresectable HCC. These results support the further development of bevacizumab combined with chemoembolization as a treatment for unresectable HCC. Cancer 2013. © 2012 American Cancer Society.