2019, Vol. 46
在中国, 原发性肝癌的死亡率位居所有癌种的第4位[1]。转移复发是肝细胞癌(hepatocellular carcinoma, HCC)死亡率居高不下的主要原因。肝内复发病灶有机会通过再次手术切除、肝移植、射频消融(radiofrequency ablation, RFA)、微波消融和放射治疗等方式得到控制, 然而对于肝外转移灶, 仍然缺少明确的治疗手段。一旦发现肝外转移, 患者的中位生存时间仅剩8.1个月左右[2]。靶向药物作为晚期肝癌的推荐治疗方案, 给肝外转移患者带来的生存获益也十分有限[3]。
根治性肝癌切除术后, 肝外转移的发生率在13.5%~36.7%[4-5]。在所有肝外转移中, 最常见的转移器官是肺(38.4%), 其次是骨(32.6%)和淋巴结(24.6%)[6]。对于肺转移的患者, 通常不建议手术切除, 仅进行姑息治疗和对症支持治疗。尽管有少数研究报道肺转移癌切除术(pulmonary metastasectomy, PME)能够延长特定亚群的肝癌患者总体生存时间[7-10], 但是这些研究多为案例报告, 例数少, 未能阐明PME的指征、疗效及预后影响因素, 因此难以指导临床肝癌肺转移精准治疗。本研究旨在探讨切除异时性肺转移肝癌患者的预后及其影响因素, 以期筛选出能够从中获益的人群, 为今后的临床决策提供一定的依据。
资料和方法实验设计 对2007年10月至2017年3月间在复旦大学附属中山医院既接受肝癌切除术又接受肺癌切除术的患者进行回顾性分析。纳入标准:(1)原发肝癌切除为根治性切除, 切除时无肝外转移和肉眼癌栓; (2) PME为异时性切除, 切除时未出现肝肺以外的器官转移, 无纵隔淋巴结转移; (3) PME时未出现肝内转移或肝内转移经综合治疗后控制良好; (4)原发肝癌和肺转移瘤的组织成分经病理证实为HCC。本研究得到中山医院伦理委员会批准。
手术与随访 患者接受根治性肝癌切除后, 根据医疗组评估和个人意愿可接受辅助性经皮肝动脉化疗栓塞(transhepatic arterial chemotherapy and embolization, TACE)治疗。患者术后平均每3个月复查一次甲胎蛋白和超声, 如有必要则进行磁共振和/或超声造影, 平均每半年复查一次胸片, 发现可疑病灶则进行胸部CT检查。若发现肝内复发, 通过再切除、肝移植、RFA和TACE等多种方式进行综合治疗。若发现肺转移, 经PET/CT等影像学检查排除其他器官转移后, 进行手术切除。首选手术方式是肺楔形切除术, 转移灶位于肺实质深处时则进行肺叶切除术, 不常规进行淋巴结清扫。在入组病例中有7例接受纵隔淋巴结清扫, 术后病理均为阴性。
观察指标 主要终点事件是死亡, 指标是“肺切除术后总体生存时间”, 定义为从首次PME至患者死亡或者末次随访的时间间隔。次要终点事件是复发转移, 肝癌切除术后复发转移的指标是“无瘤间隔时间(disease-free interval, DFI)”, 定义为原发肝癌切除术至首次确诊肝癌复发的时间间隔; PME后复发转移的指标是“肺切除术后无瘤生存时间”, 定义为首次PME至术后首次确诊肿瘤复发转移或死亡或末次随访的时间间隔。
统计学分析 等级资料用百分率表示, 连续变量用x±s和/或中位数(四分位数)表示。通过Kaplan-Meier方法估计生存率, 通过Log-Rank方法对变量的生存预后进行单因素分析, 通过Cox比例风险模型进行多因素分析。采用SPSS 20.0软件进行统计分析, P＜0.05为差异有统计学意义。
结果PME前基线特征 根据本院肝外科随访信息库, 在2007年10月至2017年3月期间接受根治性肝切除术的患者中, 347例有肺转移记录, 其中63例于本院行PME。共有42例患者符合入组标准, 38例男性, 4例女性, 行肺切除时的平均年龄为(53.2±11.7)岁(表 1)。原发肝癌的平均数量为(1.8±1.6)个, 平均大小为(7.6±3.9) cm, 肺转移癌的平均数量为(1.4±0.8)个, 平均大小为(2.5±2.0) cm。肝切除术前和肺切除术前甲胎蛋白的中位数分别为348.5(14.5, 3 473.5) ng/mL和47.7(4.9, 208.1) ng/mL。PME前有2例患者曾接受肺转移瘤局部治疗, 其中1例为RFA, 另1例为支气管动脉化疗栓塞。肝切除术后有18例患者出现肝内复发, 复发病灶经过肝移植(1例)、手术切除(6例)、RFA(4例)和TACE(7例)等方式综合治疗后均控制良好。肝切除术后的中位DFI为13.6 (5.8~35.4)个月。
| Parameters | Description form | Value |
| Sex | Male [n (%)] | 38 (90.5) |
| Age (y) | Mean±SD | 53.2±11.7 |
| Primary HCC in liver | ||
| AFP (ng/mL) | Median (Q1, Q3) | 348.5 (14.5, 3473.5) |
| > 20 [n (%)] | 29 (69.0) | |
| > 100 [n (%)] | 23 (54.8) | |
| HBsAg | Positive (%) | 33 (78.6) |
| Tumor number | Median (Q1, Q3) | 1(1, 2) |
| Mean±SD | 1.8±1.6 | |
| Largest diameter (cm) | Median (Q1, Q3) | 7.3 (5.0, 10) |
| Mean±SD | 7.6±3.9 | |
| Vascular invasion | Yes (%) | 21 (50) |
| Edmondson grade | Ⅲ-Ⅳ (%) | 21 (50) |
| Cirrhosis | Yes (%) | 22 (52.4) |
| Adjuvant TACE | Yes (%) | 25 (59.5) |
| DFI | Median (Q1, Q3) | 13.6 (5.8, 35.4) |
| < 12 mo (%) | 22 (52.4) | |
| Metastatic HCC in lung | ||
| AFP (ng/mL)a | Median (Q1, Q3) | 47.7 (4.9, 208.1) |
| > 20 [n (%)] | 21 (54.8) | |
| > 100 [n (%)] | 11 (26.2) | |
| Tumor number in lung | Median (Q1, Q3) | 1 (1, 2) |
| Mean±SD | 1.4±0.8 | |
| Largest diameter (cm) | Median (Q1, Q3) | 2.0 (1.2, 3.0) |
| Mean±SD | 2.5±2.0 | |
| Number of involved lung lobe | ≥2 [n (%)] | 10 (23.8) |
| Unilateral or bilateral of tumor | Bilateral [n (%)] | 1 (2.4) |
| AFP:Alpha-fetoprotein; HBsAg:Hepatitis B surface antigen; DFI:Disease-free interval; TACE:Transhepatic arterial chemotherapy and embolization.aAFP data was missing in 4 cases before pulmonary metastasectomy (PME). | ||
PME后复发和生存情况 42例患者接受肺转移癌切除术后无围手术期死亡, 术后中位随访时间39.4个月(29.8~49.0个月)。截至末次随访, 累计死亡19例, 复发转移29例, 存活且无复发转移12例。PME后的1年、2年、3年和5年总体生存率分别为88.0%、60.5%、55.3%和33.2%。根据PME后复发转移最先出现的部位进行分类:肝内复发17例, 肝外转移11例, 其中肺转移7例, 脑转移2例, 淋巴结1例, 骨转移1例, 腹腔转移1例。肺切除后的1年、2年、3年和5年无瘤生存率分别为56.6%、39.0%、27.9%和18.6%。术后再次出现肺转移的患者共有12例(28.6%, 12/42), 其中7例为单纯肺转移, 另外5例患者伴有肝内复发, 针对二次肺转移病灶的治疗方式包括手术切除、RFA、放射治疗、经皮支气管动脉放疗栓塞和PD1药物治疗。接受(4例)和未接受(8例)二次肺转移手术切除的患者, 他们二次肺转移后的2年生存率分别为77.8%±19.6%和25.7%±17.4%。
PME后生存的影响因素 单因素分析提示(表 2), 肺切除术后总体生存的危险因素有DFI＜12个月(P=0.009)、肺转移瘤累及两个肺叶(P=0.038)和双侧肺(P < 0.001);肺切除术后无瘤生存的危险因素有DFI＜12个月(P=0.043)和HBsAg阳性(P=0.007)。虽然受限于病例数量未能达到统计学意义, 但是原发肝癌数量≥2个(P=0.054)和最大值径＞5 cm (P=0.080)仍有可能分别是PME总体生存和无瘤生存的潜在影响因素。对有多个肺转移瘤的患者进行亚组分析, 是否累及一个以上肺叶和是否累及双侧肺对生存的差异均无统计学意义。多因素分析提示, DFI＜12个月(HR=4.50, 95%CI:1.45~13.95, P=0.009)和肺转移瘤累及双侧肺(HR=24.83, 95%CI:1.54~399.77, P=0.023)是总体生存的独立危险因素; DFI＜12个月(HR=2.22, 95%CI:1.03~4.79, P=0.042)和HBsAg阳性(HR=4.71, 95%CI:1.40~15.85, P=0.012)是无瘤生存的独立危险因素。
| Characteristics | No. | OS after PME | DFS after PME | |||||
| 2-year (%) | 5-year (%) | P | 2-year (%) | 5-year (%) | P | |||
| Sex | ||||||||
| Female | 4 | 75.0 | NA | 0.974 | 75.0 | NA | 0.187 | |
| Male | 38 | 63.9 | 34.0 | 35.0 | 17.0 | |||
| Age (at the time of PME) | ||||||||
| ≤55 y | 20 | 58.2 | 43.7 | 0.417 | 35.0 | 18.8 | 0.432 | |
| > 55 y | 22 | 71.3 | 36.3 | 42.7 | 22.2 | |||
| AFP (before live resection) | ||||||||
| ≤100 ng/mL | 19 | 63.2 | 16.4 | 0.510 | 32.0 | 0.0 | 0.103 | |
| > 100 ng/mL | 23 | 66.9 | 43.4 | 46.0 | 40.0 | |||
| HBsAg | ||||||||
| Negative | 9 | 88.9 | 44.4 | 0.099 | 77.8 | 38.9 | 0.007 | |
| Positive | 33 | 57.9 | 30.0 | 28.0 | 14.0 | |||
| Number of primary HCC | ||||||||
| 1 | 29 | 67.1 | 47.9 | 0.054 | 39.1 | 23.3 | 0.173 | |
| ≥2 | 13 | 60.4 | 10.8 | 38.5 | NA | |||
| Largest diameter of primary HCC | ||||||||
| ≤5 cm | 10 | 44.7 | 44.7 | 0.546 | 12.3 | NA | 0.080 | |
| > 5 cm | 32 | 71.0 | 32.3 | 46.5 | 21.4 | |||
| Vascular invasion of primary HCC | ||||||||
| No | 21 | 64.3 | 38.6 | 0.717 | 40.5 | 17.8 | 0.726 | |
| Yes | 21 | 65.8 | 26.3 | 37.6 | 26.0 | |||
| Edmondson grade of primary HCC | ||||||||
| Ⅰ-Ⅱ | 21 | 65.3 | 31.7 | 0.816 | 42.1 | 30.9 | 0.676 | |
| Ⅲ-Ⅳ | 21 | 64.7 | 34.7 | 35.9 | 12.4 | |||
| Liver cirrhosis | ||||||||
| No | 20 | 60.0 | 28.6 | 0.224 | 45.0 | 22.9 | 0.359 | |
| Yes | 22 | 70.0 | 35.0 | 33.4 | NA | |||
| Adjuvant TACE after liver resection | ||||||||
| No | 17 | 62.5 | 23.9 | 0.546 | 38.0 | 8.1 | 0.835 | |
| Yes | 25 | 67.0 | 40.8 | 39.7 | 30.3 | |||
| Intrahepatic recurrence, before PME | ||||||||
| No | 18 | 69.5 | 42.3 | 0.406 | 48.5 | 21.2 | 0.168 | |
| Yes | 24 | 59.0 | 16.6 | 26.5 | 17.6 | |||
| DFI | ||||||||
| ＜12 mo | 22 | 52.1 | 10.8 | 0.009 | 26.3 | 14.6 | 0.043 | |
| ≥12 mo | 20 | 79.1 | 56.5 | 53.3 | 25.2 | |||
| AFPa (before PME) | ||||||||
| ≤100 ng/mL | 27 | 72.7 | 34.9 | 0.196 | 42.8 | 17.7 | 0.575 | |
| > 100 ng/mL | 11 | 43.6 | NA | 27.3 | NA | |||
| Number of pulmonary metastatic HCC | ||||||||
| 1 | 30 | 71.9 | 34.8 | 0.167 | 44.9 | 19.6 | 0.334 | |
| ≥2 | 12 | 48.2 | 37.5 | 25.0 | 16.7 | |||
| Largest diameter of pulmonary metastatic HCC | ||||||||
| ≤3 cm | 34 | 66.0 | 38.8 | 0.956 | 39.8 | 26.5 | 0.698 | |
| > 3 cm | 8 | 60.6 | 20.2 | 37.5 | 12.5 | |||
| Number of involved lung lobe | ||||||||
| 1 | 32 | 73.6 | 36.1 | 0.038 | 39.2 | 17.1 | 0.963 | |
| 2 | 10 | 37.7 | 25.1 | 38.2 | 25.5 | |||
| Laterality of tumor distribution | ||||||||
| Unilateral | 41 | 66.6 | 34.0 | < 0.001 | 40.0 | 19.0 | 0.340 | |
| Bilateral | 1 | NA | NA | NA | NA | |||
| Resection range of lung surgery | ||||||||
| Wedge | 38 | 63.9 | 40.0 | 0.912 | 40.5 | 28.0 | 0.313 | |
| Lobectomy | 4 | 75.0 | 0.0 | 25.0 | 0.0 | |||
| Resection approach | ||||||||
| Open | 4 | 75.0 | 0.0 | 0.943 | 25.0 | 0.0 | 0.543 | |
| VAST | 38 | 63.8 | 39.9 | 40.6 | 28.1 | |||
| AFP:Alpha-fetoprotein; HBsAg:Hepatitis B surface antigen; NA:Not available; DFI:Disease-free interval; VAST:Video-assisted thoracoscopic surgery.aAFP data was missing in 4 cases before PME. | ||||||||
手术切除是根治性治疗HCC的主要手段。即使接受根治性肝癌切除术, 患者的5年复发率仍高达72.7%[11]。随着肝癌综合治疗的理念和手段日益进步, 针对肝内复发灶的治疗策略不断完善, 肝移植、复发再切除和局部治疗等方法, 有效延长了患者的长期生存[12-18]。然而, 如何治疗肝外转移瘤, 甚至是否应该进行外科干预, 仍存在很大的争议, 肝外转移依然是HCC患者获得长期生存的主要障碍。肺是最常发生肝癌转移的器官, 关于PME的研究多见于案例报道, 但其预后价值仍不明确。有些患者切除肺转移灶后能够长期生存[19-20], 而对于另一些患者, 手术获益非常有限。为了更好地筛选出适合PME的HCC患者, 本研究对42例肝癌切除术后因肺转移行肺癌切除术的病例进行回顾性分析。研究发现, PME后HCC患者的2年和5年总体生存率分别为60.5%和33.2%, 无瘤生存率分别为39.0%和18.6%, DFI＜12个月和双侧肺转移是肺切除术后总体生存的独立危险因素, DFI＜12个月和HBsAg阳性是无瘤生存的独立危险因素。
目前, 判断PME可行性的主要依据有原发肿瘤可控制、肺转移瘤可全部切除、没有肺外转移以及没有更好的治疗方式[21]。基于国际肺转移瘤切除登记信息的研究提示, 肺转移瘤数量越少, 出现得越晚, 肺切除术后的存活时间越长[22-23]。HCC肺转移瘤切除的相关研究较少, 因而也常采用上述指标进行手术评估。DFI是较为公认的预后指标, 然而其定义在各项研究中并不一致。有研究将DFI的起点定义为, 针对原发肿瘤的末次治疗[24], 如此定义可以纳入更多的病例, 比如仅接受局部治疗的非切除病例, 但是不能保证实现根治性治疗; 有研究将DFI的终点定义为肺转移出现的时间[25], 常见于联合多癌种的肺转移病例(如肠癌肺转、肉瘤肺转移、生殖细胞肿瘤肺转移等)的病例分析。在本研究中, DFI遵循无瘤(disease free)的原意, 定义为原发肝癌根治性切除至任何部位确诊复发转移的时间间隔[26]。本研究发现, DFI＜12个月同时是PME后总体生存和无瘤生存的独立危险因素, 这一点和多数研究一致[27-28]。个别研究认为肝内复发先于肺转移出现, 是肺切除术后总体生存和无瘤生存的危险因素[26]。在本研究中, 肺切除术前是否出现肝内复发和预后无关。因此, 在肝内复发肿瘤控制良好的情况下, 影响肝癌肺转移切除术预后的是肝癌复发转移的时间早晚, 而不是首发部位。
本研究未能证实肺转移瘤数量和大小的预后价值, 却发现了肺转移瘤累及范围和长期生存密切相关。转移瘤累及两个肺叶和累及双侧肺都是总体生存的危险因素, 其中累及双侧肺是独立危险因素。虽然累及单个肺叶的患者接受肺切除术的效果更优, 但是对于多发转移癌来说, 无论局限于一个肺叶还是累及两个肺叶, 其预后并无差异。在一些个案报道中, 出现双侧肺转移的患者也可获得长期生存[9, 29-30], 根据Nakagawa等[31]、Kuo等[32]和本研究的结果, 仍然不建议累及双侧肺的患者接受PME。一项样本量为11 950例的研究表明[33]HBV阳性HCC患者的术后复发率显著高于未感染肝炎病毒的患者, Kwon等[34]的研究发现HBV感染是PME后的独立预后因素。在本研究中, HBsAg阳性也是PME后无瘤生存的危险因素。
有研究报道PME前甲胎蛋白水平较高是预后的危险因素, 所选取的阈值包括100 ng/mL[32, 35]、400 ng/mL[36-37]和500 ng/mL[38], 然而本研究没有发现甲胎蛋白水平和预后之间的相关性。也有研究认为, PME后甲胎蛋白的预测价值较术前更高[35], 在本研究中, 术后甲胎蛋白的检测时间不一致且缺失数据较多, 因此未纳入该指标。
考虑到肿瘤内在的生物学特性可能会影响肺切除术后的长期生存[39-40], 而且在其他同类研究中原发肿瘤的信息通常缺失, 因此本研究将资料完整的肝癌原发灶特征也纳入分析。尽管统计学上没有显著性差异, 本研究仍提出了原发肝癌的数量和直径分别有影响PME后总体生存和无瘤生存的可能性, 这种可能性还有待更大样本量研究的证实。
根据本研究的结果, 胸腔镜和开胸手术治疗肺转移瘤的预后相似, 楔形切除和肺叶切除的预后也没有差异。从减小创伤和保存肺功能的角度考虑, 应鼓励进行胸腔镜下肺楔形切除术。本研究提示, PME后有28.6%的患者再次出现肺转移, 接受二次PME患者的2年生存率为77.8%, 而未接受二次PME的仅为25.7%, 因此二次PME仍然可以使患者获益。首次PME采用微创和楔形切除的方式, 也为施行二次PME创造了有利条件。
尽管本研究对筛选适合行PME的肝癌转移患者有提示性价值, 但是仍存在不足。首先, 回顾性研究本质不可避免地存在偏倚, 有可能会影响结果; 其次, 本研究样本量较少, 可能掩盖了潜在的预后指标; 最后, 本研究并非比较性研究, 证据等级较低。
本研究提示DFI长和累及单侧单个肺叶能够给接受PME的HCC患者带来更大的生存获益, 而对于DFI短和HBsAg阳性的患者有必要密切随访, 以便及时发现再发病灶并进行综合处治。本研究初步提示, 除了无肝内复发或者肝内复发控制良好, 能够完整切除转移灶, 肝癌术后异时性PME的潜在手术指征还应包括DFI≥12个月和肺转移瘤局限于单个肝段。为了进一步探索验证肝癌肺转移切除术的适应证, 未来更大样本量的比较性研究仍然十分必要。
| [1] |
CHEN W, ZHENG R, BAADE PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2): 115-132.
[DOI]
|
| [2] |
UCHINO K, TATEISHI R, SHⅡNA S, et al. Hepatocellular carcinoma with extrahepatic metastasis:clinical features and prognostic factors[J]. Cancer, 2011, 117(19): 4475-4483.
[DOI]
|
| [3] |
CHEN J, LU S, ZHANG Y, et al. Sorafenib monotherapy versus sorafenib combined with regional therapies for hepatocellular carcinoma patients with pulmonary oligometastases:a propensity score-matched analysis[J]. J Cancer, 2018, 9(10): 1745-1753.
[DOI]
|
| [4] |
CHUA TC, MORRIS DL. Exploring the role of resection of extrahepatic metastases from hepatocellular carcinoma[J]. Surg Oncol, 2012, 21(2): 95-101.
[DOI]
|
| [5] |
NATSUIZAKA M, OMURA T, AKAIKE T, et al. Clinical features of hepatocellular carcinoma with extrahepatic metastases[J]. J Gastroenterol Hepatol, 2005, 20(11): 1781-1787.
[DOI]
|
| [6] |
WU W, HE X, ANDAYANI D, et al. Pattern of distant extrahepatic metastases in primary liver cancer:a SEER based study[J]. J Cancer, 2017, 8(12): 2312-2318.
[DOI]
|
| [7] |
SUGA A, YAMADA S, TAKEICHI H, et al. Recurrence in regional pulmonary lymph nodes after surgery for isolated pulmonary metastasis from hepatocellular carcinoma[J]. Gen Thorac Cardiovasc Surg, 2016, 64(6): 351-354.
[DOI]
|
| [8] |
MIZUGUCHI S, NISHIYAMA N, IZUMI N, et al. Clinical significance of multiple pulmonary metastasectomy for hepatocellular carcinoma[J]. World J Surg, 2016, 40(2): 380-387.
[DOI]
|
| [9] |
OGAWA T, SATOH D, MATSUKAWA H, et al. Outcome of pulmonary metastasectomy for hepatocellular carcinoma[J]. Gan To Kagaku Ryoho, 2015, 42(12): 1494-1496.
[URI]
|
| [10] |
ZHOU YM, ZHANG XF, YU F, et al. Efficacy of surgical resection for pulmonary metastases from hepatocellular carcinoma[J]. Med Sci Monit, 2014, 20: 1544-1549.
[DOI]
|
| [11] |
PORTOLANI N, CONIGLIO A, GHIDONI S, et al. Early and late recurrence after liver resection for hepatocellular carcinoma:prognostic and therapeutic implications[J]. Ann Surg, 2006, 243(2): 229-235.
[DOI]
|
| [12] |
YAGI R, MIDORIKAWA Y, MORIGUCHI M, et al. Liver resection for recurrent hepatocellular carcinoma to improve survivability:a proposal of indication criteria[J]. Surgery, 2018, 163(6): 1250-1256.
[DOI]
|
| [13] |
ALI R, RIAZ A, GABR A, et al. Clinical outcomes of Y90 radioembolization for recurrent hepatocellular carcinoma following curative resection[J]. Eur J Nucl Med Mol Imaging, 2017, 44(13): 2195-2202.
[DOI]
|
| [14] |
YONG CC, TSAI MC, LIN CC, et al. Comparison of salvage living donor liver transplantation and local regional therapy for recurrent hepatocellular carcinoma[J]. World J Surg, 2016, 40(10): 2472-2480.
[DOI]
|
| [15] |
WANG P, LI H, SHI B, et al. Prognostic factors in patients with recurrent hepatocellular carcinoma treated with salvage liver transplantation:a single-center study[J]. Oncotarget, 2016, 7(23): 35071-35083.
[PubMed]
|
| [16] |
SU TS, LIANG P, LU HZ, et al. Stereotactic body radiation therapy for small primary or recurrent hepatocellular carcinoma in 132 Chinese patients[J]. J Surg Oncol, 2016, 113(2): 181-187.
[DOI]
|
| [17] |
ZHANG TT, LUO HC, CUI X, et al. Ultrasound-guided percutaneous microwave ablation treatment of initial recurrent hepatocellular carcinoma after hepatic resection:long-term outcomes[J]. Ultrasound Med Biol, 2015, 41(9): 2391-2399.
[DOI]
|
| [18] |
MISE Y, HASEGAWA K, SHINDOH J, et al. The feasibility of third or more repeat hepatectomy for recurrent hepatocellular carcinoma[J]. Ann Surg, 2015, 262(2): 347-357.
[DOI]
|
| [19] |
SHIH KL, CHEN YY, TENG TH, et al. Long-term survival in a patient with repeated resections for lung metastasis after hepatectomy for ruptured hepatocellular carcinoma:a case report[J]. J Med Case Rep, 2008, 2: 222.
[DOI]
|
| [20] |
MAEDA T, OHCHI T, DOI K, et al. A case of successfully repeated resections of pulmonary metastasis after hepatectomy of hepatocellular carcinoma[J]. Gan To Kagaku Ryoho, 2008, 35(12): 2207-2209.
[PubMed]
|
| [21] |
PETRELLA F, DIOTTI C, RIMESSI A, et al. Pulmonary metastasectomy:an overview[J]. J Thorac Dis, 2017, 9(Suppl 12): S1291-S1298.
[URI]
|
| [22] |
PASTORINO U, BUYSE M, FRIEDEL G, et al. Long-term results of lung metastasectomy:prognostic analyses based on 5206 cases[J]. J Thorac Cardiovasc Surg, 1997, 113(1): 37-49.
[DOI]
|
| [23] |
PASTORINO U. The development of an international registry[J]. J Thorac Oncol, 2010, 5(6 Suppl 2): S196-S197.
[URI]
|
| [24] |
KUO TM, CHANG KM, CHENG TI, et al. Clinical factors predicting better survival outcome for pulmonary metastasectomy of hepatocellular carcinoma[J]. Liver Cancer, 2017, 6(4): 297-306.
[DOI]
|
| [25] |
HAN KN, KIM YT, YOON JH, et al. Role of surgical resection for pulmonary metastasis of hepatocellular carcinoma[J]. Lung Cancer, 2010, 70(3): 295-300.
[DOI]
|
| [26] |
YOON YS, KIM HK, KIM J, et al. Long-term survival and prognostic factors after pulmonary metastasectomy in hepatocellular carcinoma[J]. Ann Surg Oncol, 2010, 17(10): 2795-2801.
[DOI]
|
| [27] |
TAKAHASHI Y, IKEDA N, NAKAJIMA J, et al. Prognostic analysis of surgical resection for pulmonary metastasis from hepatocellular carcinoma[J]. World J Surg, 2016, 40(9): 2178-2185.
[DOI]
|
| [28] |
HAU HM, SCHMELZLE M, BENZING C, et al. Pulmonary metastasectomy for metastasized hepatocellular carcinoma after liver resection and liver transplantation:a single center experience[J]. Z Gastroenterol, 2016, 54(1): 31-39.
[PubMed]
|
| [29] |
CHEN YJ, HSU HS, HSIEH CC, et al. Pulmonary metastasectomy for hepatocellular carcinoma[J]. J Chin Med Assoc, 2004, 67(12): 621-624.
[URI]
|
| [30] |
NAKAMURA M, NAGANO H, WADA H, et al. A case of hepatocellular carcinoma with multiple lung, spleen, and remnant liver metastasis successfully treated by combination chemotherapy with the novel oral DPD-inhibiting chemotherapeutic drug S-1 and interferon-alpha[J]. J Gastroenterol, 2006, 41(11): 1120-1125.
[DOI]
|
| [31] |
NAKAGAWA T, KAMIYAMA T, NAKANISHI K, et al. Pulmonary resection for metastases from hepatocellular carcinoma:factors influencing prognosis[J]. J Thorac Cardiovasc Surg, 2006, 131(6): 1248-1254.
[DOI]
|
| [32] |
KUO SW, CHANG YL, HUANG PM, et al. Prognostic factors for pulmonary metastasectomy in hepatocellular carcinoma[J]. Ann Surg Oncol, 2007, 14(2): 992-997.
[DOI]
|
| [33] |
UTSUNOMIYA T, SHIMADA M, KUDO M, et al. A comparison of the surgical outcomes among patients with HBV-positive, HCV-positive, and non-B non-C hepatocellular carcinoma:a nationwide study of 11, 950 patients[J]. Ann Surg, 2015, 261(3): 513-520.
[DOI]
|
| [34] |
KWON JB, PARK K, KIM YD, et al. Clinical outcome after pulmonary metastasectomy from primary hepatocellular carcinoma:analysis of prognostic factors[J]. Word J Surg, 2008, 14(37): 5717-5722.
[URI]
|
| [35] |
CHO S, RYU KM, HWANG YJ, et al. Prognostic factors for pulmonary metastasectomy in the treatment of hepatocellular carcinoma[J]. J Thorac Oncol, 2010, 5(8): 1251-1254.
[DOI]
|
| [36] |
HU Z, HUANG P, ZHOU Z, et al. Aggressive intrahepatic therapies for synchronous hepatocellular carcinoma with pulmonary metastasis[J]. Clin Transl Oncol, 2018, 20(6): 729-739.
[DOI]
|
| [37] |
BROCHARD C, HAMY A, MICHALAK S, et al. Metastatic hepatocellular carcinoma:when surgery and successive palliative treatments lead to remission[J]. Clin Res Hepatol Gastroenterol, 2014, 38(1): e19-e22.
[DOI]
|
| [38] |
OHBA T, YANO T, YOSHIDA T, et al. Results of a surgical resection of pulmonary metastasis from hepatocellular carcinoma:prognostic impact of the preoperative serum alpha-fetoprotein level[J]. Surg Today, 2012, 42(6): 526-531.
[DOI]
|
| [39] |
GWAK GY, JUNG JO, SUNG SW, et al. Long-term survival after pulmonary metastatectomy of hepatocellular carcinoma; treatment outcome or natural history?[J]. Hepatogastroenterology, 2004, 51(59): 1428-1433.
[URI]
|
| [40] |
WARMANN SW, FURTWANGLER R, BLUMENSTOCK G, et al. Tumor biology influences the prognosis of nephroblastoma patients with primary pulmonary metastases:results from SIOP 93-01/GPOH and SIOP 2001/GPOH[J]. Ann Surg, 2011, 254(1): 155-162.
[DOI]
|