肝門部膽管癌的外科治療現(xiàn)狀

晏益核，黃玉斌　綜述　蔡小勇　審校

（廣西醫(yī)科大學(xué)微創(chuàng)外科中心/第二附屬醫(yī)院 普通外科，廣西 南寧 530007）

膽管癌（cholangiocarcinoma）指來源于膽管上皮細(xì)胞的惡性腫瘤，其發(fā)生率占全部惡性腫瘤的比例低于1%[1]，占原發(fā)性肝膽惡性腫瘤比例的10%[2]，按照發(fā)生的解剖部位不同分為肝內(nèi)、肝門部及遠(yuǎn)端膽管癌，其中肝門部膽管癌（hilarcholangiocarcinoma，HC）約占50%～70%[2]，由Klatskin在1965年首次報道，又被稱為Klatskin腫瘤，外科手術(shù)是唯一治愈手段；半個多世紀(jì)以來，隨著醫(yī)學(xué)進(jìn)步，對HC疾病進(jìn)程、病理生理及腫瘤生物學(xué)的認(rèn)識也不斷提高，但是，仍然只有25%的初診患者有手術(shù)切除機(jī)會，術(shù)后5年生存率僅11%～42%[3-5]。本文將從術(shù)前準(zhǔn)備（腫瘤分期、術(shù)前治療）及外科手術(shù)（切除范圍、血管切除與重建、淋巴結(jié)清掃數(shù)目及范圍、腹腔鏡技術(shù)、肝移植應(yīng)用）對HC的外科治療現(xiàn)狀進(jìn)行闡述。

1　目前國際應(yīng)用的HC分期

Bismuth和Corlette在上世紀(jì)70年代提出Bismuth-Corlette分型，其中I型腫瘤位于肝總管、左右肝管匯合部以下，II型腫瘤侵犯匯合部但未侵及左右肝管，III型侵犯右肝管（IIIa）或左肝管（IIIb），IV型同時侵犯左右肝管[6]，該分型按照膽管受侵犯范圍分類，簡單實(shí)用，能夠指導(dǎo)手術(shù)方式選擇，目前仍然廣泛應(yīng)用于臨床，但并未提供其他信息，例如有無血管侵犯、淋巴結(jié)轉(zhuǎn)移、遠(yuǎn)處轉(zhuǎn)移、肝葉萎縮等，因此，無法準(zhǔn)確評估患者預(yù)后；之后，紀(jì)念Sloan-Kettering癌癥中心（MSKCC）的Jarnagin等[7]提出根據(jù)膽管受侵犯位置及范圍、門靜脈有無受侵犯以及有無肝葉萎縮這三個因素將HC分為T1、T2及T3期，在225例HC術(shù)前評估準(zhǔn)確率達(dá)到86%，但該分期較復(fù)雜，也未評估淋巴結(jié)及遠(yuǎn)處轉(zhuǎn)移或動脈受侵犯；美國癌癥分期聯(lián)合委員會（American Joint Commission on Cancer，AJCC）制訂了HC的TNM分期[8]，這是一個基于術(shù)后病理結(jié)果的TNM分期，能夠評估預(yù)后，但有研究[9]顯示其判定預(yù)后的價值不及MSKCC中的T分期，也無法指導(dǎo)術(shù)前可切除性評估及手術(shù)方式選擇；為了在全球范圍內(nèi)收集病例、統(tǒng)一評估HC的可切除性及預(yù)后，Deoliveira等[10]提出了綜合包括腫瘤侵犯膽管范圍（B）、門靜脈侵犯（PV）、肝動脈侵犯（HA）、殘余肝體積（V）、淋巴結(jié)轉(zhuǎn)移（N）、遠(yuǎn)處轉(zhuǎn)移（M）、以及腫瘤大?。═）、病理類型（F）、肝臟基礎(chǔ)疾?。―）等因素的分期方法，但最近研究[11]顯示該方法需要收集大量信息而限制其應(yīng)用；Boudjema等[12]提出了根據(jù)左外葉膽管匯合部是否受侵犯來判斷切除可能性的分型，該分型依據(jù)：⑴ 肝門部的解剖特點(diǎn)，左右肝管匯合部及肝總管位于肝十二指腸韌帶右側(cè)并緊鄰肝動脈右支，左肝管比右肝管長，左肝動脈位于肝十二指腸韌帶左側(cè)或肝胃韌帶、距離左右肝管匯合部較遠(yuǎn)；⑵ 左外葉是術(shù)后殘余肝體積的最低要求；⑶ 左外葉肝管匯合部受侵犯時腫瘤通常已經(jīng)范圍較廣并侵犯血管，切除可能性較小，即使通過擴(kuò)大半肝聯(lián)合血管切除及重建完成手術(shù)，但預(yù)后在大多數(shù)報道中并未改善。該分型與Bismuth分型的預(yù)測性較一致，對于可切除性判斷的準(zhǔn)確率較高，但是忽略了血管重建技術(shù)在門靜脈或肝動脈受侵犯病例中的重要作用，因此特異性較低。一些無法切除病例通過血管重建技術(shù)能夠根治，雖然有研究[13-15]證實(shí)血管切除重建后患者并未獲得滿意療效，但仍然有支持患者獲益的研究報道[16-18]，對此，將在后文中進(jìn)一步闡述。

2　術(shù)前治療

目前，HC術(shù)前膽道引流（pre-operative biliary drainage，PBD）仍存爭議，原因之一是缺乏證據(jù)支持PBD能夠減少術(shù)后病死率及提高生存率[19-21]；另一方面，經(jīng)皮肝穿刺膽道引流（percutaneous transhepatic biliary drainage，PTBD）存在1.7%～5.2%的穿刺隧道癌細(xì)胞種植率[22]，而內(nèi)鏡下鼻膽管引流（endoscopic nasobiliary drainage，ENBD）既能夠避免癌細(xì)胞種植，又較內(nèi)鏡下膽道支架（endoscopic biliary stenting，EBS）內(nèi)引流的感染率降低，似乎是最佳的PBD方式，但仍有相當(dāng)比例的ENBD引流效果不佳而需要再次行PTBD引流[8,23-25]，同時，ENBD達(dá)到減黃預(yù)期的時間比PTBD更長[8,23]。盡管PBD存在爭議，并且引流持續(xù)時間及適合手術(shù)的最佳膽紅素水平仍未達(dá)成共識，但是，對于膽管炎，擬行術(shù)前抗腫瘤治療，高膽紅素血癥引發(fā)的營養(yǎng)不良、肝腎功能不全以及行門靜脈栓塞（portal vein embolization，PVE）的患者，術(shù)前PBD仍是最佳選擇[8,26]。

正常肝臟可耐受最大切除量為20%的剩余肝體積（future liver remnant，F(xiàn)LR），而慢性肝炎或肝硬化則是40%的FLR，F(xiàn)LR不足將加大術(shù)后肝功能衰竭風(fēng)險。Makuuchi等[27]首次報道在大范圍肝切除術(shù)治療膽管癌的患者術(shù)前應(yīng)用PVE能夠增加FLR，之后，大量研究[17,28-30]證實(shí)術(shù)前PVE通過增加FLR減少術(shù)后并發(fā)癥率及病死率；但是，并未見PVE能夠增加HC患者R0切除率或增加生存率的相關(guān)報道。除此之外，聯(lián)合肝臟離斷和門靜脈結(jié)扎的兩步肝切除術(shù)（associating liver partition and portal vein ligation for staged hepatectomy，ALPPS）也用于因FLR不足而無法手術(shù)切除的HC患者。相較于PVE能夠在4～8周內(nèi)增加11.9%的FLR，ALPPS則在一期術(shù)后9 d內(nèi)使FLR增加74%，但33%～64%的并發(fā)癥率遠(yuǎn)高于16%的PVE并發(fā)癥率，因此，該項(xiàng)技術(shù)還需要進(jìn)一步評估[28,31]。

3　手術(shù)切除范圍

R0切除是影響HC預(yù)后的重要因素之一[4-5,17]，因此，能否達(dá)到R0切除決定了外科手術(shù)切除范圍。通過對切除組織的病理學(xué)檢查發(fā)現(xiàn)浸潤癌在膽管近切緣沿縱軸的粘膜下浸潤達(dá)到0.6～18.8 mm，非浸潤癌的表淺侵犯長度達(dá)到（54±19）mm[32]；此外，術(shù)中膽管切緣的冷凍切片檢查準(zhǔn)確率、敏感性及特異性分別是56.5%、75.0%、46.7%[33]，近期1篇報道[34]也證實(shí)膽管切緣的冷凍檢查存在敏感性較低、假陰性結(jié)果的高風(fēng)險以及陰性切緣的二次獲得率低的缺點(diǎn)，因此，臨床價值有限；基于此，在膽腸吻合技術(shù)可行及減少潛在并發(fā)癥的前提下，盡可能多地獲得膽管近端切緣長度才能夠保證高的R0切除率。另一方面，肝門部膽管癌因?yàn)槟懝鼙谳^薄以及特殊的解剖位置而較容易侵犯膽管周圍結(jié)構(gòu)以及向肝實(shí)質(zhì)侵犯，聯(lián)合大范圍肝切的肝外膽管切除能夠提高R0切除率[4,17,35-36]。

對于Bismuth I/II型腫瘤，有研究[36-37]認(rèn)為對乳頭型的T1及Tis期腫瘤行肝外膽管切除加或不加部分肝切除即可，但是，外科醫(yī)師無法在術(shù)前及術(shù)中準(zhǔn)確判斷腫瘤TNM分期，而乳頭型只占HC病理組織分型的5%～10%，其余是＞70%的硬化型以及20%的結(jié)節(jié)型[8]，因此，聯(lián)合大范圍肝切除術(shù)逐漸成為主流，其中，尾狀葉（I段）因?yàn)榫o貼肝門而受腫瘤沿膽管浸潤或是直接侵犯肝實(shí)質(zhì)的幾率極大，因此，大范圍肝切除術(shù)需要聯(lián)合I段切除[17,20,36]。然而，考慮到大范圍肝切除術(shù)后肝功能衰竭發(fā)生率增加，有報道[36,38-39]對于Bismuth I/II型、T1及T2期的III型,甚至IV型腫瘤，應(yīng)用小范圍中央?yún)^(qū)肝切除，包括I段切除，I段和IV（IVb）段切除，I段、IV（IVb）段和Ⅴ段切除，以及包括I段、IV（IVb）段、Ⅴ段和VIII段的肝中葉切除，雖然對于這一手術(shù)方式仍存有爭議，其R0切除率及預(yù)后仍需多中心研究支持，但是該術(shù)式對于降低術(shù)前PBD率、術(shù)后并發(fā)癥率及病死率方面的作用是值得肯定的。

聯(lián)合大范圍肝切除術(shù)對于Bismuth III/IV型腫瘤的手術(shù)方式通常在IIIa及IV型（病變以右肝為主）中選擇右半肝或擴(kuò)大右半肝切除，在IIIb及IV型（病變以左肝為主）中選擇左半肝或擴(kuò)大左半肝切除，但是，右半肝及擴(kuò)大右半肝切除術(shù)后病死率比較左半肝及擴(kuò)大左半肝切除增高，同時，有報道對于病變左肝為主的病例擴(kuò)大左半肝切除也能獲得高的R0切除率[40]，并且左半肝及擴(kuò)大左半肝切除對于IIIb型與右肝切除對于IIIa及IV型在R0切除率及生存率的比較無明顯差異，而術(shù)后病死率減低[41]，因此，手術(shù)方式的選擇應(yīng)該結(jié)合病變位置、預(yù)計殘余肝臟體積、肝臟基礎(chǔ)病變以及手術(shù)醫(yī)師經(jīng)驗(yàn)來共同決定。

4　聯(lián)合門靜脈、肝動脈切除與重建

如前文所述，雖然不少研究[15,18]證實(shí)聯(lián)合門靜脈切除及重建沒有增加術(shù)后并發(fā)癥率及病死率，但是患者的生存率也未從中獲益[13-15]；然而，這些研究當(dāng)中也有闡述行門靜脈切除重建的病例往往腫瘤分期更晚，即腫瘤生物學(xué)行為更具有浸潤性[15]，這些病例即使與沒有門靜脈切除重建病例的生存率相同，但該群患者仍然是獲益的，因此，門靜脈切除重建在經(jīng)驗(yàn)豐富的專業(yè)中心仍然被推崇，并且也有支持患者術(shù)后生存率獲益的研究報道[16-18,42-43]。而肝動脈切除重建術(shù)后并發(fā)癥率，包括血栓形成、狹窄等血管特異性并發(fā)癥，其他非特異性并發(fā)癥率及病死率均較門靜脈切除重建增高[13,20,42-44]，因此，該技術(shù)在HC的手術(shù)切除中并不做常規(guī)推薦；但是，與門靜脈切除重建患者的腫瘤分期較晚相似，該群患者術(shù)后生存是否也能從中獲益仍需要更多論證，同時，該技術(shù)在專業(yè)中心開展，隨著術(shù)者手術(shù)例數(shù)增加及選擇經(jīng)過嚴(yán)格評估后的合適病例，并發(fā)癥率及病死率逐漸在可控制范圍[42,44]。

5　淋巴結(jié)清掃數(shù)目與范圍

大量研究[4-5,17,45-47]證實(shí)區(qū)域淋巴結(jié)轉(zhuǎn)移（N1）是與R0切除一樣影響HC手術(shù)切除預(yù)后的獨(dú)立危險因素，淋巴結(jié)轉(zhuǎn)移的HC術(shù)后5年生存率低于25%[4,17,46]。Mao等[46]研究發(fā)現(xiàn)在N0的HC中淋巴結(jié)清掃數(shù)目＞13個預(yù)后會優(yōu)于清掃數(shù)目＜3個，而N1（膽囊管、膽總管、肝動脈及門靜脈周圍淋巴結(jié)陽性）與N2（主動脈旁、腔靜脈旁、腸系膜上動脈和/或腹腔動脈淋巴結(jié)陽性）的預(yù)后沒有明顯差異，但多于3個陽性淋巴結(jié)及陽性率＞0.27的病例預(yù)后顯著差過＜3個及＜0.27，因此，清掃13個淋巴結(jié)應(yīng)該作為腫瘤準(zhǔn)確分期的要求，并且，預(yù)后應(yīng)由轉(zhuǎn)移淋巴結(jié)的數(shù)目及陽性率而不是位置所決定。Kambakamba等[45]認(rèn)為清掃淋巴結(jié)數(shù)目應(yīng)該至少7個才能對預(yù)后準(zhǔn)確分期，而＞15個淋巴結(jié)也并不能提高陽性發(fā)現(xiàn)率。Giuliante等[47]報道陽性率超過0.2可作為影響預(yù)后的獨(dú)立因素，但陽性率受清掃淋巴結(jié)總數(shù)影響，應(yīng)達(dá)到5個以上。大多數(shù)外科醫(yī)師推崇清掃范圍包括肝十二指腸韌帶、肝總動脈旁及胰腺旁，不主張行腹主動脈旁淋巴結(jié)清掃，因?yàn)檫@不能提高預(yù)后[4,42,46,48]。

6　腹腔鏡技術(shù)應(yīng)用

腹腔鏡技術(shù)在HC中的應(yīng)用始于腫瘤探查分期，14%～45%的病例通過腹腔鏡探查可發(fā)現(xiàn)肝臟或腹膜轉(zhuǎn)移，準(zhǔn)確率達(dá)32%～71%[20,49]。此外，腹腔鏡下門靜脈結(jié)扎能獲得與PVE相似的效果[49]，完全腹腔鏡或機(jī)器人輔助膽腸吻合也用于晚期梗阻患者的姑息治療，并發(fā)癥率低、生活質(zhì)量提高[50-51]。至于完全或輔助下的腹腔鏡根治性切除，盡管有相關(guān)病例報道[52-54]，但是否符合聯(lián)合尾狀葉切除及淋巴結(jié)清掃的原則，仍存有爭議，期待更多病例研究證實(shí)。然而，隨著腹腔鏡技術(shù)在肝膽胰外科應(yīng)用的發(fā)展，在嚴(yán)格挑選的HC病例中，遵循根治性原則的前提下應(yīng)用腹腔鏡切除術(shù)，也能夠達(dá)到理想的效果[55-56]。

7　肝移植在HC中應(yīng)用

聯(lián)合新輔助放化療的肝移植應(yīng)用于適應(yīng)證嚴(yán)格的HC患者，5年無瘤生存率達(dá)到59%～82%，并且在合并硬化性膽管炎的患者中預(yù)后好于單純手術(shù)切除[57-60]。適應(yīng)證包括無法切除的直徑≤3cm的病灶且沒有肝內(nèi)及肝外轉(zhuǎn)移，有區(qū)域淋巴結(jié)轉(zhuǎn)移的患者在移植前經(jīng)過腹腔鏡探查排除。目前，沒有明確證據(jù)支持可以手術(shù)切除的患者能夠從肝移植中獲益，而對于可能切除的患者，選擇手術(shù)切除還是肝移植仍然困難，有待更多臨床研究確定[59]。

8　展　望

HC外科治療在不斷發(fā)展，更加強(qiáng)調(diào)臨床證據(jù)來選擇治療方案，而在精準(zhǔn)醫(yī)學(xué)時代，證據(jù)來源應(yīng)該更多地依據(jù)腫瘤的生物學(xué)特征，憑借以無創(chuàng)或微創(chuàng)方式獲得的腫瘤細(xì)胞分子標(biāo)志來制定基因分型，更準(zhǔn)確地指導(dǎo)外科手術(shù)方案的選擇，從而讓更多HC患者獲益。

[1]Siegel R,Naishadham D,Jemal A.Cancer statistics,2013[J].CA Cancer J Clin,2013,63(7):11–30.doi: 10.3322/caac.21166.

[2]Razumilava N,Gores GJ.Cholangiocarcinoma[J].Lancet,2014,383(9935):2168–2179.doi: 10.1016/S0140–6736(13)61903–0.

[3]Zhang W,Yan LN.Perihilar cholangiocarcinoma: Current therapy[J].World J Gastrointest Pathophysiol,2014,5(3):344–354.doi: 10.4291/wjgp.v5.i3.344.

[4]Nagino M,Ebata T,Yokoyama Y,et al.Evolution of surgical treatment for perihilar cholangiocarcinoma: a single-center 34-year review of 574 consecutive resections[J].Ann Surg,2013,258(1):129–140.doi: 10.1097/SLA.0b013e3182708b57.

[5]Buettner S,Margonis GA,Kim Y,et al.Conditional probability of long-term survival after resection of hilar cholangiocarcinoma[J].HPB (Oxford),2016,18(6):510–517.doi: 10.1016/j.hpb.2016.04.001.

[6]Bismuth H,Corlette MB.Intrahepatic cholangioenteric anastomosis in carcinoma of the hilus of the liver[J].Surg Gynecol Obstet,1975,140(2):170–178.

[7]Jarnagin WR,Fong Y,DeMatteo RP,et al.Staging,resectability,and outcome in 225 patients with hilar cholangiocarcinoma[J].Ann Surg,2001,234(4):507–517.

[8]Mansour JC,Aloia TA,Crane CH,et al.Hilar cholangiocarcinoma:expert consensus statement[J].HPB (Oxford),2015,17(8):691–699.doi: 10.1111/hpb.12450.

[9]Zaydfudim VM,Clark CJ,Kendrick ML,et al.Correlation of staging systems to survival in patients with resected hilar cholangiocarcinoma[J].Am J Surg 2013,206(2):159–165.doi:10.1016/j.amjsurg.2012.11.020.

[10]Deoliveira ML,Schulick RD,Nimura Y,et al.New staging system and a registry for perihilar cholangiocarcinoma[J].Hepatology,2011,53(4):1363–1371.doi: 10.1002/hep.24227.

[11]Ismael HN,Loyer E,Kaur H,et al.Evaluating the Clinical Applicability of the European Staging System for Perihilar Cholangiocarcinoma[J].J Gastrointest Surg,2016,20(4):741–747.doi: 10.1007/s11605–016–3075–5.

[12]Boudjema K,Sulpice L,Garnier S,et al.A simple system to predict perihilar cholangiocarcinoma resectability[J].J Gastrointest Surg,2013,17(7):1247–1256.doi: 10.1007/s11605–013–2215–4.

[13]Abbas S,Sandroussi C.Systematic review and meta-analysis of the role of vascular resection in the treatment of hilar cholangiocarcinoma[J].HPB (Oxford),2013,15(7):492–503.doi:10.1111/j.1477–2574.2012.00616.x.

[14]Hoffmann K,Luible S,Goeppert B,et al.Impact of portal vein resection on oncologic long-term outcome in patients with hilar cholangiocarcinoma[J].Surgery,2015,158(5):1252–1260.doi:10.1016/j.surg.2015.04.032.

[15]Wu XS,Dong P,Gu J,et al.Combined portal vein resection for hilar cholangiocarcinoma: a meta-analysis of comparative studies[J].J Gastrointest Surg,2013,17(6):1107–1115.doi: 10.1007/s11605–013–2202–9.

[16]de Jong MC,Marques H,Clary BM,et al.The impact of portal vein resection on outcomes for hilar cholangiocarcinoma: a multiinstitutional analysis of 305 cases[J].Cancer,2012,118(19):4737–4747.oi: 10.1002/cncr.27492.

[17]Igami T,Nishio H,Ebata T,et al.Surgical treatment of hilar cholangiocarcinoma in the "new era": the Nagoya University experience[J].J Hepatobiliary Pancreat Sci,2010,17(4):449–454.doi: 10.1007/s00534–009–0209–0.

[18]Chen W,Ke K,Chen YL.Combined portal vein resection in the treatment of hilar cholangiocarcinoma: a systematic review and meta-analysis[J].Eur J Surg Oncol,2014,40(5):489–495.doi:10.1016/j.ejso.2014.02.231.

[19]Poruk KE,Pawlik TM,Weiss MJ.Perioperative Management of Hilar Cholangiocarcinoma[J].J Gastrointest Surg,2015,19(10):1889–1899.doi: 10.1007/s11605–015–2854–8.

[20]Bhardwaj N,Garcea G,Dennison AR,et al.The Surgical Management of Klatskin Tumours: Has Anything Changed in the Last Decade?[J].World J Surg,2015,39(11):2748–2756.doi:10.1007/s00268–015–3125–2.

[21]Farges O,Regimbeau JM,Fuks D,et al.Multicentre European study of preoperative biliary drainage for hilar cholangiocarcinoma[J].Br J Surg,2013,100(2):274–283.doi: 10.1002/bjs.8950.

[22]Hwang S,Song GW,Ha TY,et al.Reappraisal of percutaneous transhepatic biliary drainage tract recurrence after resection of perihilar bile duct cancer[J].World J Surg,2012,36(2):379–385.doi: 10.1007/s00268–011–1364–4.

[23]蔡云峰,蘇樹英,崔偉珍,等.可切除肝門部膽管癌術(shù)前膽道引流方式的選擇[J].中國普通外科雜志,2011,20(8):844–847.Cai YF,Su SY,Cui WZ,et al.Selection of preoperative biliary drainage procedure for resectable hilar cholangiocarcinoma[J].Chinese Journal of General Surgery,2011,20(8):844–847.

[24]Kawashima H,Itoh A,Ohno E,et al.Preoperative endoscopic nasobiliary drainage in 164 consecutive patients with suspected perihilar cholangiocarcinoma: a retrospective study of efficacy and risk factors related to complications[J].Ann Surg,2013,257(1):121–127.doi: 10.1097/SLA.0b013e318262b2e9.

[25]Hameed A,Pang T,Chiou J,et al.Percutaneous vs.endoscopic pre-operative biliary drainage in hilar cholangiocarcinoma - a systematic review and meta-analysis [J].HPB (Oxford),2016,18(5):400–410.doi: 10.1016/j.hpb.2016.03.002.

[26]Paik WH,Loganathan N,Hwang JH.Preoperative biliary drainage in hilar cholangiocarcinoma: When and how?[J].World J Gastrointest Endosc,2014,6(3):68–73.doi: 10.4253/wjge.v6.i3.68.

[27]Makuuchi M,Thai BL,Takayasu K,et al.Preoperative portal embolization to increase safety of major hepatectomy for hilar bile duct carcinoma: a preliminary report[J].Surgery,1990,107(5):521–527.

[28]Abulkhir A,Limongelli P,Healey AJ,et al.Preoperative portal vein embolization for major liver resection: a meta-analysis[J].Ann Surg,2008,247(1):49–57.

[29]Hwang S,Ko GY,Kim MH,et al.Preoperative Left Portal Vein Embolization for Left Liver Resection in High-Risk Hepatobiliary Malignancy Patients[J].World J Surg,2016,40(11):2758–2765.

[30]邢冬娟,徐愛民,易濱,等.術(shù)前門靜脈栓塞術(shù)在肝門部膽管癌擴(kuò)大肝切除術(shù)中的應(yīng)用研究[J].肝膽外科雜志,2011,19(6):415–419.doi:10.3969/j.issn.1006–4761.2011.06.006.Xing DJ,Xu AM,Yi B,et al.Portal vein embolization before extensive hepatectomy in patientes with hilar cholangiocarcinoma[J].Journal of Hepatobiliary Surgery,2011,19(6):415–419.doi:10.3969/j.issn.1006–4761.2011.06.006.

[31]Eshmuminov D,Raptis DA,Linecker M,et al.Meta-analysis of associating liver partition with portal vein ligation.and portal vein occlusion for two-stage hepatectomy[J].Br J Surg,2016,103(13):1768–1782.doi: 10.1002/bjs.10290.

[32]Igami T,Nagino M,Oda K,et al.Clinicopathologic study of cholangiocarcinoma with superficial spread[J].Ann Surg,2009,249(2):296–302.doi: 10.1097/SLA.0b013e318190a647.

[33]Okazaki Y,Horimi T,Kotaka M,et al.Study of the intrahepatic surgical margin of hilar bile duct carcinoma[J].Hepatogastroenterology,2002,49(45):625–627.

[34]Mantel HT,Westerkamp AC,Sieders E,et al.Intraoperative frozen section analysis of the proximal bile ducts in hilar cholangiocarcinoma is of limited value[J].Cancer Med,2016,5(7):1373–1380.doi: 10.1002/cam4.693.

[35]陳孝平,黃志勇,陳義發(fā),等.肝門部膽管癌根治術(shù)肝切除范圍的合理選擇[J].中國普通外科雜志,2013,22(1):8–9.doi:10.7659/j.issn.1005–6947.2013.01.003.Chen XP,Huang ZY,Chen YF,et al.Rational extent of hepatic resection in radical surgery for hilar cholangiocarcinoma[J].Chinese Journal of General Surgery,2013,22(1):8–9.doi:10.7659/j.issn.1005–6947.2013.01.003.

[36]Xiang S,Lau WY,Chen XP.Hilar cholangiocarcinoma:controversies on the extent of surgical resection aiming at cure[J].Int J Colorectal Dis,2015,30(2):159–171.doi: 10.1007/s00384–014–2063–z.

[37]Otani K,Chijiiwa K,Kai M,et al.Role of hilar resection in the treatment of hilar cholangiocarcinoma[J].Hepatogastroenterology,2012,59(115):696–700.doi: 10.5754/hge09725.

[38]Tan JW,Hu BS,Chu YJ,et al.One-stage resection for Bismuth type IV hilar cholangiocarcinoma with high hilar resection and parenchyma-preserving strategies: a cohort study[J].World J Surg,2013,37(3):614–621.doi: 10.1007/s00268–012–1878–4.

[39]Wang S,Tian F,Zhao X,et al.A new surgical procedure"dumbbell-form resection" for selected hilar cholangiocarcinomas with severe jaundice: comparison with hemihepatectomy[J].Medicine (Baltimore),2016,95(2):e2456.doi: 10.1097/MD.0000000000002456.

[40]Hosokawa I,Shimizu H,Yoshidome H,et al.Surgical strategy for hilar cholangiocarcinoma of the left-side predominance: current role of left trisectionectomy[J].Ann Surg,2014,259(6):1178–1185.doi:10.1097/SLA.0000000000000584.

[41]魯正,王冬冬.Bismuth-Corlette III、IV型肝門部膽管癌的手術(shù)治療方式[J].中華外科雜志,2016,54(7):488–491.doi:10.3760/cma.j.issn.0529–5815.2016.07.003.Lu Z,Wang DD.Operation treatment method of Bismuth-Corlette III,IV hilar cholangiocarcinoma[J].Chinese Journal of Surgery,2016,54(7):488–491.doi:10.3760/cma.j.issn.0529–5815.2016.07.003.

[42]Groeschl RT,Nagorney DM.Portal vein reconstruction during surgery for cholangiocarcinoma[J].Curr Opin Gastroenterol,2016,32(3):216–224.doi: 10.1097/MOG.0000000000000259.

[43]郁曉峰,龔先鋒,張洋,等.聯(lián)合血管切除在手術(shù)治療肝門部膽管癌中作用的Meta分析[J].中國普通外科雜志,2016,25(2):162–174.doi:10.3978/j.issn.1005–6947.2016.02.002.Yu XF,Gong XF,Zhang Y,et al.Combined vascular resection in surgical treatment of hilar cholangiocarcinoma: a Meta-analysis[J].Chinese Journal of General Surgery 2016,25(2):162–174.doi:10.3978/j.issn.1005–6947.2016.02.002.

[44]Nagino M,Nimura Y,Nishio H,et al.Hepatectomy with simultaneous resection of the portal vein and hepatic artery for advanced perihilar cholangiocarcinoma: an audit of 50 consecutive cases[J].Ann Surg,2010,252(1):115–123.doi: 10.1097/SLA.0b013e3181e463a7.

[45]Kambakamba P,Linecker M,Slankamenac K,et al.Lymph node dissection in resectable perihilar cholangiocarcinoma: a systematic review[J].Am J Surg,2015,210(4):694–701.doi: 10.1016/j.amjsurg.2015.05.015.

[46]Mao K,Liu J,Sun J,et al.Patterns and prognostic value of lymph node dissection for resected perihilar cholangiocarcinoma[J].J Gastroenterol Hepatol,2016,31(2):417–426.doi: 10.1111/jgh.13072.

[47]Giuliante F,Ardito F,Guglielmi A,et al.Association of Lymph Node Status With Survival in Patients After Liver Resection for Hilar Cholangiocarcinoma in an Italian Multicenter Analysis[J].JAMA Surg,2016,151(10):916–922.doi: 10.1001/jamasurg.2016.1769.

[48]Aoba T,Ebata T,Yokoyama Y,et al.Assessment of nodal status for perihilar cholangiocarcinoma: location,number,or ratio of involved nodes[J].Ann Surg,2013,257(4):718–725.doi: 10.1097/SLA.0b013e3182822277.

[49]Cho A,Yamamoto H,Kainuma O,et al.Laparoscopy in the management of hilar cholangiocarcinoma[J].World J Gastroenterol,2014,20(41):15153–15157.doi: 10.3748/wjg.v20.i41.15153.

[50]Toumi Z,Aljarabah M,Ammori BJ.Role of the laparoscopic approach to biliary bypass for benign and malignant biliary diseases: a systematic review[J].Surg Endosc,2011,25(7):2105–2116.doi: 10.1007/s00464–010–1544–6.

[51]Lai EC,Tang CN.Robot-assisted laparoscopic hepaticojejunostomy for advanced malignant biliary obstruction[J].Asian J Surg,2015,38(4):210–213.doi: 10.1016/j.asjsur.2015.01.010.

[52]Yu H,Wu SD,Chen DX,et al.Laparoscopic resection of Bismuth type I and II hilar cholangiocarcinoma: an audit of 14 cases from two institutions[J].Dig Surg,2011,28(1):44–49.doi:10.1159/000322398.

[53]Gumbs AA,Jarufe N,Gayet B.Minimally invasive approaches to extrapancreatic cholangiocarcinoma[J].Surg Endosc,2013,27(2):406–414.doi: 10.1007/s00464–012–2489–8.

[54]Machado MA,Makdissi FF,Surjan RC,et al.Laparoscopic resection of hilar cholangiocarcinoma[J].J Laparoendosc Adv Surg Tech A,2012; 22(10):954–956.doi: 10.1089/lap.2012.0339.

[55]Lee W,Han HS,Yoon YS,et al.Laparoscopic resection of hilar cholangiocarcinoma[J].Ann Surg Treat Res,2015,89(4):228–232.doi: 10.4174/astr.2015.89.4.228.

[56]Puntambekar S,Sharma V,Kumar S,et al.Laparoscopic Management of Hilar Cholangiocarcinoma: a Case Report[J].Indian J Surg,2016,78(1):57–59.doi: 10.1007/s12262–015–1345–1.

[57]Darwish Murad S,Kim WR,Harnois DM,et al.Efficacy of neoadjuvant chemoradiation,followed by liver transplantation,for perihilar cholangiocarcinoma at 12 US centers[J].Gastroenterology,2012,143(1):88–98.doi: 10.1053/j.gastro.2012.04.008.

[58]Darwish Murad S,Heimbach JK,Gores GJ,et al.Excellent quality of life after liver transplantation for patients with perihilar cholangiocarcinoma who have undergone neoadjuvant chemoradiation[J].Liver Transpl,2013,19(5):521–528.doi:10.1002/lt.23630.

[59]Croome KP,Rosen CB,Heimbach JK,et al.Is liver transplantation appropriate for patients with potentially resectable de novo hilar cholangiocarcinoma?[J].J Am Coll Surg,2015,221(1):130–139.doi: 10.1016/j.jamcollsurg.2015.01.064.

[60]Mantel HT,Westerkamp AC,Adam R,et al.Strict selection alone of patients undergoing liver transplantation for hilar cholangiocarcinoma is associated with improved survival[J].PLoS One,2016,11(6):e0156127.doi: 10.1371/journal.pone.0156127.