楊念欽　王一唯　孫立安　郭劍明　王　杭

(復(fù)旦大學(xué)附屬中山醫(yī)院泌尿外科　上?！?00032)

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T1b期腎細(xì)胞癌保留腎單位手術(shù)的臨床價(jià)值

楊念欽王一唯孫立安郭劍明王杭△

(復(fù)旦大學(xué)附屬中山醫(yī)院泌尿外科上海200032)

【摘要】目的探討T1b期腎細(xì)胞癌 (renal cell carcinoma,RCC) 行各種保留腎單位手術(shù) (nephron sparing surgery,NSS)的安全性與可行性。方法回顧性分析2011年1月至2013年12月復(fù)旦大學(xué)附屬中山醫(yī)院 50 例行開放、腹腔鏡及機(jī)器人輔助下NSS的T1b期RCC患者臨床資料及隨訪情況。結(jié)果50例患者均成功行NSS,手術(shù)時(shí)間 (70～210) min,平均 (122.8±44.1) min。阻斷腎血流38例,熱缺血時(shí)間 (20～47) min,平均 (29.0±8.5) min。術(shù)中出血量 30～1 100 mL,平均 (196.6±212.8) mL,腫瘤RENAL評(píng)分4～10,平均7.3±1.6,術(shù)前血肌酐42～150 μmol/L,平均 (77.4±22.0) μmol/L;術(shù)后住院5～46天,平均 (8.4±6.5)天。術(shù)后病理示:透明細(xì)胞癌45例,嫌色細(xì)胞癌3例,乳頭狀癌2例。50例患者術(shù)后1周、3個(gè)月和6個(gè)月腎功能復(fù)查,肌酐分別為 (87.3±11.6)μmol/L、 (82.5±10.8)μmol/L和(79.7±12.1)μmol/L,血尿素氮分別為 (5.7±1.6) mmol/L、 (5.2±1.3) mmol/L和(5.1±1.2) mmol/L,與術(shù)前比較差異無統(tǒng)計(jì)學(xué)意義。結(jié)論NSS既能有效切除腫瘤,又能保留部分腎單位,是一種有效的治療T1b期RCC可行的選擇,尤其對(duì)雙側(cè)腎腫瘤或者孤立性腎臟腎腫瘤。

【關(guān)鍵詞】腎部分切除術(shù);T1b期;腎細(xì)胞癌

*This work was supported by the National Natural Science Foundation of China (81472376).

根據(jù)中華醫(yī)學(xué)會(huì)泌尿外科疾病診療指南,腎癌直徑在4～7 cm之間為T1b期腎細(xì)胞癌(renal cell carcinoma,RCC),既往的經(jīng)驗(yàn)一般行根治性腎切除手術(shù),認(rèn)為保留腎單位 (nephron sparing surgery,NSS)手術(shù)僅適用于小于4 cm的腎腫瘤。但是,近年來國內(nèi)外文獻(xiàn)均指出[1-3],即使腫瘤直徑大于4 cm,也應(yīng)該盡可能行NSS。國外大樣本長期隨訪結(jié)果顯示,NSS與腎癌根治手術(shù)治療效果相當(dāng),但在總體生存率、腎功能保存、術(shù)后生活質(zhì)量等方面優(yōu)勢明顯[4-7]。NSS的目的是保留腎功能,并且不影響腫瘤學(xué)治療結(jié)果。精確的手術(shù)切除、最大限的保留腎單位及術(shù)中腎實(shí)質(zhì)缺血時(shí)間的控制是NSS的關(guān)鍵。腎單位保留的數(shù)量和質(zhì)量是術(shù)后腎功能最為重要的決定因素。但T1b期RCC常因?yàn)槟[瘤體積大、位置深,手術(shù)難度增加,國內(nèi)外對(duì)于腹腔鏡及機(jī)器人輔助下腹腔鏡NSS治療T1b 期RCC的報(bào)道較少。復(fù)旦大學(xué)附屬中山醫(yī)院在2011年至2013年間,通過多種方式共完成T1b期RCC的NSS 50例,現(xiàn)報(bào)告如下。

資 料 和 方 法

研究對(duì)象復(fù)旦大學(xué)附屬中山醫(yī)院泌尿外科2011年1月至2013年12月間共完成T1b期RCC的NSS 50例,其中男性24例,女性26例,年齡21～71歲,平均(52±12.3)歲。42例患者體檢發(fā)現(xiàn)病變,6例患者局部酸痛不適就診,2例患者因血尿就診,所有患者均行腹部B超及增強(qiáng)CT檢查,24例同時(shí)行腹部MR檢查,15例行IVU檢查;術(shù)前診斷均為腎臟實(shí)質(zhì)占位 (圖1),32例行CT 動(dòng)脈造影以了解腎動(dòng)脈是否存在分支或變異。術(shù)前均行X 線胸片、腹部B 超檢查排除轉(zhuǎn)移可能。腫瘤直徑4～7 cm,平均直徑(4.9±0.7)cm;腫瘤位于左側(cè)26例,位于右側(cè)22例,其中雙側(cè)腎腫瘤2例,功能性孤立腎患者1例。

MRI performance for low signal showed a diameter of about 6 cm solid lesion in the lower pole of the left kidney.

圖1術(shù)前腹部MRI檢查

Fig 1Preoperative abdominal MRI examination

手術(shù)方法50例患者均成功施行NSS,其中開放手術(shù)40例,腹腔鏡手術(shù)4例,機(jī)器人輔助腹腔鏡手術(shù)6例。開放手術(shù)術(shù)中阻斷腎動(dòng)脈或者腎蒂,或不阻斷腎血流,腎周放置冰屑降溫,沿腫瘤邊緣0.1～0.5 cm正常腎組織切除腫瘤及周圍組織。取創(chuàng)面基底部組織行切緣病理檢查。腎集合系統(tǒng)破損者以3-0微喬縫合,創(chuàng)面以3-0微喬縫扎止血,再以2-0 微喬對(duì)合縫合。創(chuàng)面以凝血膠和止血紗布覆蓋。腹腔鏡手術(shù)和機(jī)器人輔助腹腔鏡手術(shù)采用經(jīng)由腹腔途徑,均阻斷腎動(dòng)脈或者腎蒂,操作步驟與文獻(xiàn)報(bào)道[8-10]類似,集合系統(tǒng)破損以3-0微喬縫合,創(chuàng)面以2-0微喬對(duì)合縫合。

結(jié)果

50例圍手術(shù)期患者均成功行NSS,手術(shù)時(shí)間70～210 min,平均 (122.8±44.1)min,阻斷腎血流38例,熱缺血時(shí)間20～47 min,平均 (29.0±8.5) min;術(shù)中出血量30～1 100 mL,平均 (196.6±212.8) mL,腫瘤RENAL評(píng)分4～10,平均7.3±1.6,術(shù)前血肌酐42～150 μmol/L,平均 (77.4±22.0) μmol/L;術(shù)后住院天數(shù)5～46天,平均 (8.4±6.5)天。術(shù)后病理:透明細(xì)胞癌45例,嫌色細(xì)胞癌3例,乳頭狀癌2例。術(shù)后發(fā)生腎假性動(dòng)脈瘤出血1例,行超選擇腎動(dòng)脈栓塞后治愈;1例功能性孤立腎患者術(shù)后3天肌酐升高至800 μmol/L,行血液透析治療;下肢深靜脈血栓1例,給予抗凝藥物,制動(dòng)后好轉(zhuǎn),長期口服抗凝藥物,傷口感染2例,傷口定期換藥后均痊愈。

隨訪結(jié)果所有患者均獲得隨訪,隨訪時(shí)間6～41個(gè)月,中位隨訪時(shí)間16個(gè)月。隨訪內(nèi)容包括定期每3個(gè)月復(fù)查血尿常規(guī)、肝腎功能、胸部X光攝片或CT、腹部臟器B超檢查等。50例患者術(shù)后1周、3個(gè)月和6個(gè)月腎功能復(fù)查,肌酐分別為(87.3±11.6)μmol/L、 (82.5±10.8)μmol/L和(79.7±12.1)μmol/L,血尿素氮分別為 (5.7±1.6) mmol /L、 (5.2±1.3) mmol /L和(5.1±1.2)mmol/L,與術(shù)前比較差異無統(tǒng)計(jì)學(xué)意義。1例術(shù)后血液透析患者連續(xù)透析1個(gè)月后,肌酐降至250～300 μmol/L,停止血液透析,對(duì)癥治療。1例患者術(shù)后21個(gè)月發(fā)現(xiàn)肺部轉(zhuǎn)移,進(jìn)行靶向藥物治療中。

討論

腫瘤大小曾經(jīng)是NSS的指征,既往認(rèn)為適用于小于4 cm位于腎臟一極的腎臟腫瘤,反之則是根治性腎切除的指征。但隨著研究[11-13]的深入,即使腫瘤大于4 cm,NSS遠(yuǎn)期生存率與根治性腎切除并無明顯差異。國內(nèi)外對(duì)于保留腎單位的腎部分切除術(shù)治療T1b 期RCC的報(bào)道不多[13-15],腹腔鏡腎部分切除術(shù)的關(guān)鍵是完整切除腫瘤及假包膜、縮短術(shù)中熱缺血時(shí)間、完善縫合技巧避免出血。對(duì)于腫瘤體積相對(duì)較大、位置較深、突破集合系統(tǒng)或靠近腎門血管的T1b 期RCC,機(jī)器人輔助腹腔鏡具有優(yōu)勢,但如何處理好以上幾個(gè)核心難點(diǎn)對(duì)泌尿外科醫(yī)師是巨大的挑戰(zhàn)。2010 EUA 指南中將保留腎單位的腎切除術(shù)作為治療T1期RCC的金標(biāo)準(zhǔn)：只要腫瘤完整切除,切緣厚度不影響局部復(fù)發(fā)[16]。目前的觀念認(rèn)為腫瘤大小并不是NSS的指征,只要條件 (包括手術(shù)技巧和設(shè)備)許可,即使腫瘤大于4 cm,也應(yīng)該行NSS。

T1b期RCC行NSS的關(guān)鍵點(diǎn)首先是手術(shù)指征的掌握,要評(píng)估腫瘤和腎血管尤其是腎動(dòng)脈的關(guān)系,可術(shù)前行CTA檢查,如果腫瘤累及腎動(dòng)脈主干則不適宜行NSS。但是,腎靜脈累及并不是絕對(duì)的禁忌證,可以切除部分血管壁行腎靜脈修補(bǔ),本組患者行腎靜脈修補(bǔ)2例,術(shù)后均恢復(fù)良好。需要注意的是,腫瘤和集合系統(tǒng)的關(guān)系也要詳細(xì)評(píng)估,如果累及腎盂或者腎盂輸尿管連接部則是該類手術(shù)的相對(duì)禁忌證。手術(shù)技巧也是該類手術(shù)的另一重點(diǎn),腫瘤直徑的增加導(dǎo)致切除時(shí)間延長、切除創(chuàng)面增大。如何在有限時(shí)間內(nèi)完成腫瘤切除和創(chuàng)面有效止血是手術(shù)成功的關(guān)鍵。我們的經(jīng)驗(yàn)是最好能有效阻斷腎血流,這樣在切除腫瘤時(shí)才可以保證視野的清晰。創(chuàng)面上所有血管斷端都應(yīng)該以可吸收線確切縫扎。腫瘤切除后的創(chuàng)緣必須確切對(duì)合縫合以保證局部有效的張力壓迫止血。本組患者1例術(shù)后假性動(dòng)脈瘤出血,即是術(shù)中未有效阻斷腎血流,創(chuàng)面視野不清,止血不徹底所至。在腫瘤切除后,切緣應(yīng)該多點(diǎn)取樣活檢以保證切緣陰性,如果切緣陽性則應(yīng)該果斷改行根治性腎切除術(shù)。本組所有患者均行術(shù)中快速冰凍切片以明確切緣情況,未發(fā)現(xiàn)切緣陽性患者。

T1b期RCC行NSS后的療效是另一個(gè)值得重視的問題,根據(jù)目前多項(xiàng)研究的報(bào)道[17-21],NSS與根治性腎切除術(shù)治療T1b期RCC的遠(yuǎn)期無瘤生存率無明顯差異,本組患者術(shù)后隨訪6～41個(gè)月,僅1例患者發(fā)生肺部轉(zhuǎn)移。一般認(rèn)為腎血管阻斷時(shí)間不要超過30 min,對(duì)于某些孤立腎患者,還應(yīng)盡量縮短熱缺血時(shí)間。本組1例孤立腎患者盡管術(shù)中熱缺血時(shí)間控制在30 min以內(nèi),術(shù)后仍然發(fā)生急性腎功能衰竭。

單純腹腔鏡技術(shù)應(yīng)用于T1b期RCC行NSS,由于其操作的復(fù)雜性,需要較長的學(xué)習(xí)曲線,機(jī)器人輔助腹腔鏡下T1b期RCC行NSS,可以縮短熱缺血時(shí)間及術(shù)者的學(xué)習(xí)曲線,具有良好的前景。

NSS是一種有效治療T1b期RCC的方法,尤其對(duì)雙側(cè)腎腫瘤或者孤立性腎臟腎腫瘤,既能有效切除腫瘤,又能保留部分腎單位,是一種可行的選擇。腫瘤大小不是NSS的禁忌證,只要手術(shù)技術(shù)上可行,則可考慮NSS。機(jī)器人輔助腹腔鏡NSS能減少患者創(chuàng)傷,縮短術(shù)者學(xué)習(xí)曲線,在將來可能會(huì)成為T1b期RCC行NSS的首選術(shù)式。

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The clinical value of nephron sparing surgery for T1b stage renal cell carcinoma

YANG Nian-qin, WANG Yi-wei, SUN Li-an, GUO Jian-ming, WANG Hang△

(DepartmentofUrology,ZhongshanHospital,FudanUniversity,Shanghai200032,China)

【Abstract】ObjectiveTo investigate the safety and feasibility of T1b stage renal cell carcinoma (RCC) underwent nephron sparing surgery (NSS).MethodsFifty cases of T1b stage RCC treated with NSS through open、laparoscopic and robotic assisted laparoscopic resection in Zhongshan hospital from Jan.,2011 to Dec., 2013 were included and retrospectively analysized.ResultsFifty patients were successfully performed through NSS with meas operation time of (122.8±44.1) min (70-210 min). Mean intra-operative blood loss of (196.6±212.8) mL (30-1 100 mL), mean preoperative serum creatinine of (77.4±22.0) μmol/L (42-150 μmol/L),and mean postoperative hospital stay of (8.4±6.5) days (5-46 days). In 38 cases with interruption of renal blood flow during operation, mean warm ischemia time was (29.0±8.5) min (20-47 min). The postoperative pathology indicated that 45 cases were clear cell carcinoma,3 cases were chromophobe renal cell carcinoma, 2 cases were papillary carcinoma.The 50 cases post-operation follow-up renal function, one week, three months and six months,the serum creatinine were (87.3±11.6) μmol/L, (82.5±10.8) μmol/L, (79.7±12.1) μmol/L; blood urea nitrogen were (5.7±1.6) mmol/L,(5.2±1.3) mmol/L and (5.1±1.2) mmol / L,respectively.It has no significant difference with the pre-operation. ConclusionsTumor resection and renal function blood urea nitrogen levels. partial preservation can be both achieved by NSS. Therefore it is an alternative treatment for T1b RCC, especially for those cases with solitary kidney or bilateral RCC.

【Key words】nephron sparing surgery;T1b stage;renal cell carcinoma

【中圖分類號(hào)】R 692

【文獻(xiàn)標(biāo)識(shí)碼】A

doi:10.3969/j.issn.1672-8467.2016.01.007

(收稿日期:2015-04-16;編輯:王蔚)

國家自然科學(xué)基金 (81472376)

△Corresponding authorE-mail:wang.hang@zs-hospital.sh.cn