維持性血液透析的并發(fā)癥和防治

1、,,肺 癌,,流行病學(xué)epidemiology,美國(guó)癌癥死亡率 (1992-1996),,,,,,,,,,,,,,,,,,,,,0,10,20,30,40,50,60,70,80,直腸癌,胰腺癌,肺癌,前列腺癌,乳腺癌,卵巢癌,,,男,,女,死亡率 100,000 人/每年,,Ries et al 1999,,,美國(guó)肺癌發(fā)病率和死亡率 (1973-1996),,,,,,,,,,,,,,,,,,,,,,,,,,,,,1

2、0,50,100,Incidence - males,Mortality - males,Incidence - females,Mortality - females,Rate per 100,000 people(log scale),1974,76,78,80,82,84,86,88,90,92,94,96,Year of diagnosis/death,,,,,,,,Ries et al 1999,,,肺癌發(fā)生率：病理類(lèi)型

3、、性別、種族 (1973-1996),,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,60,10,1,94-6,85-7,1973-5,,,,男性黑人,男性白人,女性黑人,女性白人,Year of diagnosis,鱗癌,腺癌,大細(xì)胞癌,,,,,,,,,,,,,,小細(xì)胞癌,94-6,85-7,73-5,Rate per 100,000people (log scale),,,,,,,,,,,,,,94

4、-6,85-7,73-5,94-6,85-7,73-5,,,Wingo et al 1999,,,肺癌的流行病學(xué)特點(diǎn),90-92年肺癌占惡性腫瘤死因第1位的省市:上 海: 43.53/10萬(wàn)天 津: 38.86遼 寧: 32.07黑龍江: 29.06吉 林: 28.06云 南: 23.07北 京: 22.25內(nèi)蒙古: 22.04,肺癌的流行病學(xué)特點(diǎn),解剖和病理Anatomy and

5、Pathology,肺癌的分類(lèi)學(xué),按部位分:中央型周?chē)桶瓷飳W(xué)分:小細(xì)胞肺癌: (15-20%)非小細(xì)胞肺癌: (80-85%)鱗癌 腺癌 大細(xì)胞癌 腺鱗癌 其它,肺癌病理類(lèi)型,鱗癌 0.30-0.35腺癌 0.35-0.40大細(xì)胞癌 0.10小細(xì)胞癌 0.20-0.25,癥狀和診斷S

6、ymptoms and Diagnosis,肺癌的癥狀學(xué),發(fā)生發(fā)展 表現(xiàn) 肺癌形成 無(wú)癥狀累及小支氣管 咳嗽累及粘膜微血管 血痰侵及胸膜胸壁 胸悶胸痛

7、阻塞支氣管 氣促發(fā)熱胸膜播散 胸水非特異性癥狀: 食欲不振 體重下降,肺癌的癥狀學(xué),外侵和轉(zhuǎn)移癥狀上腔靜脈綜合征Horner’s SyndromePancoast’s Syndrome肺癌伴隨癥狀:肺性骨關(guān)節(jié)病類(lèi)癌綜合征男性乳房發(fā)育,,肺癌的主要癥狀和體征,,,,,,,,

8、,,,,,0,20,40,60,80,100,咯血,納差,疼痛,咳嗽,呼吸困難,患者(%),Hollen et al 1999,,,,,,Transthoracic needle aspiration (TTNA) of a non-small cell Pancoast tumor,,,肺癌的診斷學(xué),幾個(gè)需要遵循的原則警惕經(jīng)治未愈的呼吸道癥狀注意少見(jiàn)的肺外表現(xiàn)從常規(guī)到復(fù)雜從無(wú)創(chuàng)到有創(chuàng)重視獲取病理學(xué)診斷細(xì)胞學(xué),組織學(xué),非小細(xì)

9、胞肺癌的診斷,Physical examination,Detect signs,Visualize and sample mediasturial lymph nodes,Detect position, size, number of tumors,Detect chest wall invasion mediastinal lymphodenopathy distant metastases,Lymph node staging,

10、Detect changes in hormone production, and hematological manifestations of lung cancer,Precise location of tumor obtain biopsy,Chest X-ray,CT scan,PET scan,Laboratory analysis,Bronchoscopy,Mediastinoscopy,FNA,Cytology,,,

11、,,,,,,,NCCN Guidelines 2000,,,診斷（Diagnosis） 1、CXR，CT， B 2、對(duì)肺周?chē)筒∽兘?jīng)皮肺穿刺是合適的，但非 強(qiáng)制性，特別是既往胸片檢查無(wú)病變者。 B 3、CT提示縱隔淋巴結(jié)>1 cm（短徑）應(yīng)行縱隔 鏡檢，前縱隔切開(kāi)活檢或穿刺。 B

12、 BTS Guidelines Thorax 2001,56 89-108,非小細(xì)胞肺癌 X線胸片,,,,非小細(xì)胞肺癌 CT 掃描,,,,,縱隔鏡檢查,分期和預(yù)后staging and prognostication,,Mountain 1997,非小細(xì)胞肺癌分期,DiseaseEarlyLocalizedAdvanced,Stage

13、0IAIBIIAIIBIIIAIIIBIV,TNMTIS N0 M0 (carcinoma in situ)T1 N0 M0T2 N0 M0T1 N1 M0T2 N1 M0T3 N0 M0T3 N1 M0T1-3 N2 M0T4, Any N, M0Any T, N3, M0Any T, Any N, M1,,,,,,非小細(xì)胞肺癌分期,,Stage 0,Stage IA,Stage I

14、IB,Stage IIIB,Stage IV,,Lymph nodes,,,Main bronchus,Contralateral lymph node,,Metastasis to distant organs,,,,,,,,,,,,,,,,,Invasion of chest wall,,,非小細(xì)胞肺癌：臨床分期與預(yù)后,,,1 year,,3 years,,5 years,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,

15、,,,,,,,,,,,,0,10,20,30,40,50,60,70,80,90,100,IA,IB,IIA,T2N1M0,IV,IIB,IIIA,IIIB,,,,,,,Clinical stage at presentation,Survival (%),,Mountain 1997,,,T3N0M0,T3N1M0,T1-3N2M0,T4,N3,,,,Probability of survival according to clini

16、cal stage,非小細(xì)胞肺癌: 其他影響預(yù)后因素可手術(shù) (0-IIIA期),肺部癥狀腫瘤的最大徑erbB-2, p53過(guò)表達(dá)血管侵犯 腫瘤血管形成,,,,Harpole 1995,非小細(xì)胞肺癌: 其他影響預(yù)后因素不可手術(shù) ( IIIB-IV期),PS評(píng)分年齡和性別體重下降轉(zhuǎn)移灶LDH, AKP（堿性磷酸酶）,血鈣，血紅蛋白含鉑化療方案,,Albain et al 1991,,,治療Treatment,肺癌治療

17、思維決策,先進(jìn)行肺癌的生物學(xué)分類(lèi)小細(xì)胞肺癌非小細(xì)胞肺癌再根據(jù)資料作肺癌的分期決定肺癌的治療方案治療結(jié)束安排隨防計(jì)劃,非小細(xì)胞肺癌：治療概況,腫瘤局限手術(shù)腫瘤范圍較大化療,放療 (手術(shù))晚期腫瘤化療,,PDQ Guidelines,非小細(xì)胞肺癌的治療： 0期,肺葉，肺段切除術(shù)，或楔形切除術(shù)根治性化療（有手術(shù)禁忌者）內(nèi)鏡下光動(dòng)力學(xué)治療 (療效待評(píng)估),,PDQ Guidelines,,,非小細(xì)胞肺癌的治療：

18、I期 和 II期,肺葉切除術(shù)或肺切除術(shù)根治性化療（有手術(shù)禁忌者）輔助化療輔助放療新輔助化療,,PDQ Guidelines,,,I期非小細(xì)胞肺癌: 手術(shù),Locoregionalrecurrencerate(per person-year),Locoregionalrecurrencerate(% of patients),,,,,,,,,,,0,10,20,30,40,50,Segmen-tectomy(n

19、=68),Lobectomy(n=105),,,,,,,,,,,,,,,,00.0,0.01,0.02,0.03,0.04,0.05,0.06,0.07,0.08,0.09,0.10,Limitedresection (n=122),Lobectomy(n=125),,,p=0.008,,Warren and Faber 1994,Ginsberg and Rubinstein1995,,,p<0.05,,,,I期和 II

20、期非小細(xì)胞肺癌:放療,Dosoretz et al 1992,,,,,,,,,,,,0,10,20,30,40,50,60,70,80,Overall,>65 Gray,<60 Gray,Radiation dose,Disease-free survival (%),,,非小細(xì)胞肺癌的治療：III期,單純手術(shù)治療 (部分 IIIA 期患者)術(shù)后放療化療 + 放療單純放療單純化療 ( IIIB期伴惡性胸腔積液）,,

21、PDQ Guidelines,,,III期非小細(xì)胞肺癌: 手術(shù)聯(lián)合其他治療,StudyPass et al 1992Roth et al 1994Rosell et al 1994,RegimensSurgery plus chemotherapy (n=13)Surgery plus radiotherapy (n=14)Surgery plus chemotherapy (n=28)Su

22、rgery alone (n=32)Surgery plus radiotherapy plus chemotherapy (n=30)Surgery plus radiotherapy (n=30),Median survival (months)28.715.66411268,p value 0.095<0.008<0.001,,,,,,,I-IIIB期非小細(xì)

23、胞肺癌: CHART,,,,,,,,,,0,10,20,30,40,50,60,70,1-year,2-year,Survival(% patients),Saunders et al 1997,p=0.004,,,,III期非小細(xì)胞肺癌:聯(lián)合放、化療,,NSCLC Collaborative Group 1995,,,IV期非小細(xì)胞肺癌的治療,化療（含鉑方案）, 有生存獲益新一代化療藥物外放射治療 (姑息治療)內(nèi)鏡下激光治療或

24、近距離化療（解除氣道阻塞）,,PDQ Guidelines,,,IV期非小細(xì)胞肺癌:聯(lián)合化療,,,,,,,,,,,,,,,,0,5,10,15,20,25,30,35,PVp,PVpm,PVe,PVeMi,FOMi/CAP,Responserate (%),p<0.001 across treatments,,,,,,,,,,,,,,,,,,,0,1,2,3,4,5,6,7,8,9,10,PVp,PVpm,PVe,PVeMi,

25、FOMi/CAP,Mediansurvival(months),p=0.61 across treatments,,Weick et al 1991,,,IV期非小細(xì)胞肺癌:新一代化療藥物,Paclitaxel, vinorelbine, docetaxel Gemcitabine, topotecan, irinotecan單藥療效優(yōu)于順鉑聯(lián)合化療：在研,,Jassem 1999,,,晚期非小細(xì)胞肺癌的聯(lián)合化療: 近年的

26、隨機(jī)試驗(yàn)(1),StudyLe Chevalier et al 1994Bonomi et al 1996Crino et al 1998Belani et al 1998 Cardenal et al 1999,RegimensVindesine/cisplatinVinorelbine/cisplatinEtoposide/cisplatinPaclitaxel (135)/cispla

27、tinPaclitaxel (250)/cisplatin/G-CSFMitomycin/ifosfamide/cisplatinGemcitabine/cisplatinEtoposide/cisplatinPaclitaxel/cisplatinEtoposide/cisplatinGemcitabine/cisplatin,Median survival (months)7.69.5*7.69.

28、5*9.9*9.68.68.27.77.28.7,1-year survival (%) 2837323739343337322632,,,,Tumor response (%)1930*12*27*32*2638*1423*21.940.6*,*p<0.05,,Gandara et al 1999,,,晚期非小細(xì)胞肺癌的聯(lián)合化療: 近年的隨

29、機(jī)試驗(yàn)(2),StudyKelly et al 1999Schiller et al 2000,RegimensVinorelbine (25)/cisplatin (100)Paclitaxel (225)/carboplatin (AUC6)Paclitaxel (135)/cisplatin (75)Gemcitabine (1000)/cisplatin (100)Docetaxel (75)

30、/cisplatin (75)Paclitaxel (225)/carboplatin (AUC6),Median survival (months)887.88.17.48.2,,,,Tumor response (%)272721.321.017.315.3,,,,Schiller et al 2000,Kelly et al 1999,非小細(xì)胞肺癌化療后復(fù)發(fā),手術(shù) (部分伴局限腦轉(zhuǎn)移灶

31、)姑息放療姑息化療內(nèi)鏡下激光治療或組織內(nèi)放療,,PDQ Guidelines,,,順鉑耐藥,Significant problem in many solid tumors, including NSCLCMultifactorial:reduced transport into cellsdeactivation by intracellular thiolsincreased DNA repairincreased

32、DNA damage tolerance,,Perez 1997,,,展望未來(lái)Future developments,非小細(xì)胞肺癌: 未來(lái)發(fā)展,目前的治療方案療效欠佳 預(yù)防 早期診斷 提高治療療效,,PDQ Guidelines,,,預(yù)防,教育避免環(huán)境致癌物，如吸煙化學(xué)預(yù)防?vitamin A異維甲酸,,,,早期診斷,阻塞性肺部疾病遺傳危險(xiǎn)因素 痰脫落細(xì)胞學(xué)分子腫瘤標(biāo)記物CT掃描PET,,Edell

33、 1997,,,治療,NSCLC,Novel biological targets,Immunology:- interleukins- interferons- vaccines,Newchemotherapydrugs,Gene therapy:- interleukins- K-ras,,,,,,,,新的化療方法,拓?fù)洚悩?gòu)酶抑制劑 新的抗葉酸劑,,,,新的生物學(xué)治療方法,表皮生長(zhǎng)因子酪氨酸激酶抑制劑