胰腺疾病-傅德良课件.ppt

1、傅 德 良胰 腺 疾 病复旦大学附属华山医院胰腺外科复旦大学胰腺病研究所学科负责人傅德良复旦大学外科系教授复旦大学外科系教授，博士生导师博士生导师华山医院胰腺外科华山医院胰腺外科 主任主任 复旦大学胰腺病研究所复旦大学胰腺病研究所 常务副所长常务副所长上海市医学领军人才上海市医学领军人才/上海市胰腺学科优秀带头人上海市胰腺学科优秀带头人上海医学会外科分会胰腺学组上海医学会外科分会胰腺学组 副组长副组长上海市抗癌协会胰腺癌专业委员会上海市抗癌协会胰腺癌专业委员会 副主任委员副主任委员中国抗癌协会胰腺癌专业委员会中国抗癌协会胰腺癌专业委员会 常委常委中国临床肿瘤协会中国临床肿瘤协会CSCOCSCO

2、胰腺癌专家委员会胰腺癌专家委员会 副主任委员副主任委员World J GastroenterolWorld J Gastroenterol (SCI)(SCI)、中华肝胆外科中华肝胆外科等等 编委编委Email:Email: 胰腺外科-科室构成博士生导师博士生导师2 2名（博士点）名（博士点）硕士生导师硕士生导师1 1名（硕士点）名（硕士点）教授教授 1主任医师主任医师2、副教授、副教授 2高年主治高年主治 2低年主治低年主治1住院医师住院医师1低年主治低年主治1低年主治低年主治1住院医师住院医师1住院医师住院医师1所有主治医师均获博士学位所有主治医师均获博士学位所有住院医师均获硕士学位所有住

3、院医师均获硕士学位胰腺的临床应用解剖生理概要The distal common bile duct and main pancreatic duct may join outside the duodenal wall to form a long common channel,within the duodenal wall to form a short common channel,or they may enter the duodenum through two distinct ostia.The pancreatic head is supplied by branches of

4、 the gastroduodenal and superior mesenteric arteries,whereas the body and tail are supplied by branches of the splenic artery.Venous drainage is to the splenic,superior mesenteric,and portal veins The major drainage of the pancreatic head and uncinate process is to the subpyloric,portal,mesenteric,m

5、esocolic,and aortocaval nodes.The pancreatic body and tail,for the most part,are drained through nodes in the celiac,aortocaval,mesenteric,and mesocolic groups and through nodes in the splenic hilum The pancreas is innervated by both sympathetic and parasympathetic components of the autonomic nervou

6、s system.The principal,and possibly only,pathway for pancreatic pain involves nociceptive fibers arising in the pancreas,The nerves of the pancreas travel with the blood vessels supplying the organ.急 性 胰 腺 炎发 病 原 因发 病 机 理NormalAcute pancreatitisJean-Louis Frossard,et al.Lancet 2008;371:14352基本病理改变临

7、床 表 现Physical Examination No obvious jaundice in skin or eyes Widespread tenderness with guarding Cullens sign Grey Turners sign Normal Bp,tachycardiaGrey Turners sign Cullens sign诊 断（1 1）胰酶测定胰酶测定:血、尿淀粉酶血、尿淀粉酶 血脂肪酶（达血脂肪酶（达1.51.5康氏单位）康氏单位）（2 2）腹腔穿刺：腹水淀粉酶测定）腹腔穿刺：腹水淀粉酶测定（3 3）B B超检查超检查：胆道病变、腹水：胆道病变、腹水（4

8、 4）CT CT：明确诊断、坏死部位、胰外侵犯程度：明确诊断、坏死部位、胰外侵犯程度（5 5）X X 线：横结肠、胃扩张、左膈肌抬高、线：横结肠、胃扩张、左膈肌抬高、胸腔积液胸腔积液 (6)(6)腹腔引流液细菌培养腹腔引流液细菌培养腹腔感染监测腹腔感染监测急性水肿性胰腺炎CT表现急性坏死性胰腺炎CT表现急性胰腺炎分类急性胰腺炎的Balthazar（CT分级评分法）Acute pancreatitis CT Severity Index(CTSI)Bradley EL 3rd.A clinically based classification system for acute pancreati

9、tis:Summary of the International Symposium on Acute Pancreatitis,Atlanta.Arch Surg.1993;128:586590.Modified from the International Association of PancreatologyBalthazar EJ.Imaging and intervention in acute pancreatitis.Radiology 1994;193:297306CT grading of severity(Balthazar)Mayerle J et al.Current

10、 management of AP.Nat Clin Pract Gastroenterol Hepatol,2005;2:473483急性胰腺炎的APACHE评分Ransons Prognostic Signs-Gallstone PancreatitisAST,aspartate transaminase;BUN,blood urea nitrogen;Ca2+,calcium;Hct,hematocrit;LDH,lactic dehydrogenase;Pao2,arterial oxygen;WBC,white blood cell count Ranson JHC,et al:Pr

11、ognostic signs and the role of operative management in acutepancreatitis.Surg Gynecol Obstet 1974;139:69-81.Ranson JHC:Etiological and prognostic factors in human acute pancreatitis:A review.Am J Gastroenterol 77:633,1982Ransons Prognostic Signs-nongallstone PancreatitisFor a diagnosis of severe acu

12、te pancreatitis in a patient with pancreatitis,three or more above criteria must be present.Ranson JHC,et al:Prognostic signs and the role of operative management in acutepancreatitis.Surg Gynecol Obstet 1974;139:69-81.Ranson JHC:Etiological and prognostic factors in human acute pancreatitis:A revie

13、w.Am J Gastroenterol 77:633,1982急性胰腺炎的临床诊断鉴 别 诊 断非手术治疗治 疗方 法手术治疗胰腺肿瘤Benign/malignantExocrine(acinar and ductal cell)Endocrine(Pancreatic islet cell tumors)内分泌肿瘤 Alpha cell Glucagon GlucagonomaBeta cell Insulin InsulinomaDelta cell Somatostatin SomatostatinomaDelta-2-cells VIP WDHA(Vipoma)G-cells Gas

14、trin ZES(Gastrinoma)胰 腺 癌恶性程度高，预后极差，社会影响很大恶性程度高，预后极差，社会影响很大胰腺癌仅占全身癌肿胰腺癌仅占全身癌肿2%，但死亡率却占，但死亡率却占6%Siegel R,et al.Cancer statistics(2011).CA Cancer J Clin.2010;61:212-236.Pancreatic cancer is the 10th most commonly diagnosed cancer and the 4th leading cause of cancer death in the United States.Ferlay J.

15、et al.Estimates of cancer incidence and mortality in Europe in 2008.Eur J Cancer,2010;46:765 781Incidence 7thMortality 5thPancreatic cancer我国胰腺癌的发病率明显上升的趋势我国胰腺癌的发病率明显上升的趋势发病率（单位：发病率（单位：/10万）万）胰腺中华内科杂志，2005；44（7）：509-513During 2002 to 2006,new cases:8190 pts in ShanghaiRough incidence：Male 13.13/1000

16、00,list in the 8th，Female:11.21/100000,list in the 7th，Incidence of pancreatic cancer increased in Shanghai(19732006)2006 incidence:12.16/10 /100000,Similar to incidence in US for patients 65yearsGenetic abnormalities in pancreatic cancers:activation of growth-promoting oncogenes,mutations that resu

17、lt in the inactivation of tumor suppressor genes,and excessive expression of growth factors or their receptors Progression model for pancreatic cancer Histological images of benign pancreatic ductal epithelial cells,progressive PanIN lesions and invasive carcinoma,with associated genetic alterations

18、.Paula Ghaneh,et al.Biology and management of pancreatic cancer.Gut 2007;56;1134-1152The progression from histologically normal ductal epithelium to low-grade pancreatic intraepithelial neoplasia(PanIN)to high-grade PanIN(left to right)is associated with the accumulation of specific genetic changes.

19、Early changes include Her-2/neu and K-ras mutations;intermediate changes include p16 mutations;and changes associated with either in situ or early invasive cancer include p53,BRCA2,and DPC4 mutations Pancreatic cancer has the highest mortality rate of all the major cancers:only 6%survive more than f

20、ive years.75%of patients with pancreatic cancer die within the first year of diagnosis.The survival rate for the disease has not improved substantially in nearly 40 years.Since 1975,the 5-year survival rate for pancreatic cancer has improved only from 3%to 6%.It is estimated that 43,140 Americans wi

21、ll be diagnosed with pancreatic cancer in 2010 and that 36,800 will die from PC.The number of new pancreatic cancer cases and the number of deaths caused by the disease are increasing not decreasing(increase by 55%between the years 2010 and 2030).胰腺癌早期诊断困难临 床 特 点（1 1）恶性程度高，早期发现困难，预后差）恶性程度高，早期发现困难，预后

22、差（2 2）多发生于头部（）多发生于头部（2/32/3），体尾部少（），体尾部少（1/31/3）（3 3）胰管癌占）胰管癌占9090，腺泡细胞癌较少，腺泡细胞癌较少（4 4）胰腺癌以淋巴转移和局部浸润为主胰腺癌以淋巴转移和局部浸润为主（5 5）胰腺癌的发病率增加，生存率低）胰腺癌的发病率增加，生存率低淋巴转移胰腺癌主要转移方式 影响手术预后的重要因素 Pawlik T M.et al,Surgery 2007;141:610-8 Isaji,Yoshifumi,et al.Pancreas,2004;3(28):231-23 Carr JA,et al.Am Surg,1999;65(12):

23、1143-1149 临 床 表 现 （1 1）上腹痛和上腹饱胀不适）上腹痛和上腹饱胀不适 （2 2）进行性梗阻性黄疸）进行性梗阻性黄疸 （3 3）突发的糖尿病、急性胰腺炎表现）突发的糖尿病、急性胰腺炎表现 （4 4）不典型的消化道症状）不典型的消化道症状 （5 5）不明原因的消瘦、乏力、后背痛）不明原因的消瘦、乏力、后背痛 （6 6）晚期表现：肿块、腹水、发热等）晚期表现：肿块、腹水、发热等原则原则：以病史采集为基础以病史采集为基础 辅以特殊实验室和影像学检查手段辅以特殊实验室和影像学检查手段 从无创到有创从无创到有创 定位、定性和分期诊断兼顾定位、定性和分期诊断兼顾临 床 诊 断胰腺癌的高危

24、因素高危人群年龄大于年龄大于4040岁，有上腹部岁，有上腹部非特异性症状者；非特异性症状者；有胰腺癌家族史者；有胰腺癌家族史者；突发糖尿病患者，特别是突发糖尿病患者，特别是不典型糖尿病；不典型糖尿病；慢性胰腺炎患者；慢性胰腺炎患者；导管内乳头状粘液瘤；导管内乳头状粘液瘤；家族性腺瘤息肉病；家族性腺瘤息肉病；远端胃大部切除者；远端胃大部切除者；胰腺囊肿患者；胰腺囊肿患者；有恶性肿瘤高危因素者；有恶性肿瘤高危因素者；诊 断 方 法（1 1）提高警惕，争取早期诊断）提高警惕，争取早期诊断（2 2）血生化检查：血尿淀粉酶、血糖、肝）血生化检查：血尿淀粉酶、血糖、肝功能异常功能异常（3 3）免疫学检查：

25、）免疫学检查：CEACEA、CACA5050、CA19-9CA19-9、PCAAPCAA、CACA125125、CACA724 724、CACA242 242（4 4）影像学检查：）影像学检查：BusBus、CTCT、ERCPERCP（MRCPMRCP）、）、PTCPTC（5 5）细针穿刺活检：脱落细胞检查、癌基因检测）细针穿刺活检：脱落细胞检查、癌基因检测 （K-rasK-ras、P53P53）胰腺癌早期诊断的水平有待提高多排螺旋多排螺旋CTCT空间分辨率高，定位诊断良好空间分辨率高，定位诊断良好良恶性病变的鉴别作良恶性病变的鉴别作用局限用局限MRI/MRCPMRI/MRCP清楚显示胰胆管结

26、构清楚显示胰胆管结构良恶性病变的鉴别作良恶性病变的鉴别作用局限用局限ERCP ERCP 可进行脱落细胞学检查以及治疗可进行脱落细胞学检查以及治疗 有创性有创性EUS/FNAEUS/FNA术前取得病理，诊断灵敏度、特术前取得病理，诊断灵敏度、特异度高异度高有创性，临床普及难有创性，临床普及难CA199CA199等等肿瘤标志物肿瘤标志物方便，安全，适合于普查方便，安全，适合于普查敏感性高敏感性高特异性较差特异性较差PET/CTPET/CT功能检测与解剖结构检测相融合功能检测与解剖结构检测相融合 有助于早期诊断的正有助于早期诊断的正确性确性胰腺癌CT成像胰腺癌CT成像门静脉期门静脉期动脉期动脉期实质

27、期实质期胰头癌的双管征胰腺血供的CT三维重建动脉血供三维重建动脉血供三维重建门静脉系统三维重建门静脉系统三维重建肠系膜上静脉重建肠系膜上静脉重建多排多排CTA可以更精确地显示胰腺小病灶，进行周围血管的三维重建可以更精确地显示胰腺小病灶，进行周围血管的三维重建Type AType BType CType DType EType FCT criteria of vascular invasion for pancreatic cancer胰头肿瘤的MR征像同一病例，同一病例，MRI T1WI 双期增强成像，动脉期和门脉期显示癌肿实双期增强成像，动脉期和门脉期显示癌肿实质部分增强，增强程度与无癌胰腺

28、相仿，坏死灶不增强（箭）。质部分增强，增强程度与无癌胰腺相仿，坏死灶不增强（箭）。T1WI增强成像 动脉期T1WI增强成像 门脉期坏死、囊变坏死、囊变T1T1低信号，低信号，T2T2高信号，不增强高信号，不增强胰头肿瘤的MR征像T1WI 平扫MRCPMRI GRE T1WI平扫显示癌肿为相对低信号，信号强度不均匀，平扫显示癌肿为相对低信号，信号强度不均匀，MRCP显示显示癌肿远端（上游）胰腺导管和胆管突然中断、扩大，即双管征（胆癌肿远端（上游）胰腺导管和胆管突然中断、扩大，即双管征（胆/胰管均突然中断、扩大）。胰管均突然中断、扩大）。双双 管管 征征磁共振胰胆管成像（MRCP）正常MRCP胰腺

29、癌MRCP壶腹癌MRCPPET-CT探测探测18F18F湮灭辐射后发射的湮灭辐射后发射的 射线射线,获获得得18F-FDG18F-FDG在体内的分布影像在体内的分布影像,反映反映体内葡萄糖代谢的状态和水平体内葡萄糖代谢的状态和水平18F-18F-氟代脱氧葡萄糖（氟代脱氧葡萄糖（18F-FDG18F-FDG）肿肿瘤显像瘤显像功能学半定量检测功能学半定量检测 SUV(standard uptake value)SUV(standard uptake value)滞留指数滞留指数(retention index,RI)(retention index,RI)BIOGRAPH 64 HDBIOGRAP

30、H 64 HD RI=(SUV RI=(SUV延迟延迟-SUV-SUV早期早期)100/SUV100/SUV早期早期,诊断精确度达到诊断精确度达到88%;88%;延迟图像可多发现肝转移、淋巴结等转移灶延迟图像可多发现肝转移、淋巴结等转移灶 The FDG is not metabolized and is trapped inside the cell allowing it to be imaged in contrast to surrounding tissuePETCTPET/CTWhole scanning of PETCT内镜超声胰腺癌的定性诊断 术中活检以明确病理诊断术中活检以明

31、确病理诊断 B B超或超或CTCT引导下经皮细针穿刺引导下经皮细针穿刺 内镜超声引导下的细针穿刺抽内镜超声引导下的细针穿刺抽吸细胞学检查（吸细胞学检查（FNAFNA）胰腺癌UICC的TNM分期 分期分期肿瘤大小肿瘤大小淋巴结转移淋巴结转移远处转移远处转移0期期TisN0M0期期T1N0M0T2N0M0期期T3N0M0期期T1N1M0T2N1M0T3N1M0a期期T4任何NM0b期期任何T任何NM1胰腺癌诊断胰腺癌诊断的JPS分期分期分期肿瘤大小淋巴结转移远处转移期TlaN0M0期T1aN1M0T1bN0,N1M0期T1a,T1bN2M0T2N0,N1M0a期 T1a,T1bN3M0T2N2M0

32、T3N0,N1M0b期T2N3M0T3N2,N3M0任何T任何NM1 化疗：介入、静脉化疗、口服化疗化疗：介入、静脉化疗、口服化疗 放疗：（术中、调强适形、伽玛刀）、放疗：（术中、调强适形、伽玛刀）、I I125125短程放疗短程放疗 支持治疗支持治疗胰腺癌的治疗Kausch-Whipple surgical procedure for pancreatic cancer Allen O Whipple,MDPyloric-preserving WhippleStandard Whipple Kausch W.Das Carcinom der Papilla Duodeni und seine

33、 radikale Entferung:beitrage klinischen.Chirurgie 1912;78:439486 Whipple AO,Parsons WB,Mullins CR.Treatment of carcinoma of the ampulla of Vater.Ann Surg 1935;102(4):763779胰腺癌手术治疗的认知To:“Surgical resection provides the only potential cure for pancreatic cancer.”胰腺癌手术方式Laparoscopic/Robotic Pancreatico

34、duodenectomySurgical Procedure for Pancreatic Cancer in Head According to the consensus conferenceA standard pancreatoduodenectomy includes regional lymphadenectomy around the duodenum and pancreas(stations 12b1,12b2,12c,13a,13b,14a,14b,17a,17b and 8a).A radical pancreatoduodenectomy involves a regi

35、onal lymphadenectomy as in a standard operation plus skeletonization of hepatic arteries,SMA between aorta and inferior pancreaticoduodenal and coeliac trunk,dissection of the anterolateral aspect of aorta and vena cava including Gerotas fascia(standard+all station 8,9,all 12,all 14,16a2,16b1).An ex

36、tended pancreatoduodenectomy includes lymphadenectomy as in the radical operation in addition to all station 16 lymph nodes.Pedrazzoli S,Beger HG,et al.Summary of an international workshop on surgical procedures in pancreatic cancer.Dig.Surg.1999;16:33745.胰体尾癌根治术（改良Appleby术）特点：切除率低特点：切除率低(5%)、难于清扫、易

37、复发、难于清扫、易复发欧洲分类欧洲分类:标准左侧胰切除术标准左侧胰切除术(SLP)和根治性左侧胰切除术和根治性左侧胰切除术(RLP)SLP 包含腹腔干、脾门、脾动脉及胰体尾下缘作区域性淋巴结切除，包含腹腔干、脾门、脾动脉及胰体尾下缘作区域性淋巴结切除，RLP 在区域性淋巴结切除的基础上加作沿肝动脉淋巴结、主动脉与下腔静脉前侧面在区域性淋巴结切除的基础上加作沿肝动脉淋巴结、主动脉与下腔静脉前侧面淋巴结淋巴结(包括包括No.16a2、16b1)包含包含Gerota筋膜的切除，左肾上腺不强求切除。筋膜的切除，左肾上腺不强求切除。高根五.胰腺癌规范化切除手术J.中国实用外科杂志,2008;28（5）:

38、354-356联合血管切除的胰头癌根治术PD with PV/SMV R&RPD with PV/SMV R&RKathleen K.Christians,et al.Surg Clin N Am,2010;90:309322Different technical options for resection and reconstruction of the SMV,PV,or SMV-PV confluenceHuashan method胰腺癌手术为主综合治疗新方法华山医院胰腺外科经验 局部进展期胰腺癌局部进展期胰腺癌 T1T13 3、与周围脏器、血管有粘连侵犯、与周围脏器、血管有粘连侵犯可

39、能，而无全身转移可能，而无全身转移 可切除性胰腺癌可切除性胰腺癌交界可切除性胰头癌“减黄介入手术”治疗新策略傅德良等傅德良等.中华消化外科，中华消化外科，2004;3:18-22倪泉兴，傅德良等倪泉兴，傅德良等.中华外科杂志，中华外科杂志，2001;39:508-510Zhang QH,et al.The Chinese-German Journal of Clinical Oncology,2003;2:82-86国内领先，国际先进国内领先，国际先进术后介入术后介入术前介入术前介入根治性手术根治性手术 可切除胰腺癌治疗新模式：“多时相介入化疗根治性手术”傅德良等傅德良等,可切除性胰腺癌多时相

40、介入综合治疗的临床研究可切除性胰腺癌多时相介入综合治疗的临床研究.外科理论与实践外科理论与实践,2006,11(6):492-495,2006,11(6):492-495 JIN Chen,Fu DL,Ni QX et al.JIN Chen,Fu DL,Ni QX et al.Chin Med J,2009;122(IF 0.81)Chin Med J,2009;122(IF 0.81)肿瘤标记物显著下降肿瘤标记物显著下降助于降低肝转移和淋巴结转移发生率助于降低肝转移和淋巴结转移发生率（34%34%vs 60 vs 6080%80%，50%50%vs 70 vs 7080%)80%)提高提高

41、5 5年生存率年生存率胰腺癌淋巴转移和微转移特性研究胰腺癌淋巴转移和微转移特性研究2004年卫生部临床重点学科项目倪泉兴，傅德良等。中华肝胆外科杂志，倪泉兴，傅德良等。中华肝胆外科杂志，2004;11(1):18-21倪泉兴，傅德良等倪泉兴，傅德良等.中华胰腺病学中华胰腺病学.2004；4(2)：90-94Brown HM,et al.J Surg Res,2001;95:141-146Vision Kestrel手术显微镜手术显微镜检出淋巴结（检出淋巴结（41.2/例）例）细胞角化蛋白细胞角化蛋白AE1/AE3T2期达期达10区域性的淋巴结清扫区域性的淋巴结清扫淋巴转移发生早、发生率高（淋巴

42、转移发生早、发生率高（64）；存在微转移）；存在微转移国内领先国内领先胰头癌的淋巴手术清扫范围standardradicalextended（Depart.of Pancreatic Surgery,Huashan Hospital（华山胰外）（华山胰外）,PDI）胰腺周围淋巴结的分布Isaji S,Kawarada Y,Uemoto S.Classification of Pancreatic Cancer:Comparison of Japanese and UICC Classifications.Pancreas 2004;28(3):231-234.Surgical procedur

43、e of carcinoma of the head of pancreas:modified extended lymphadenectomyAll lymphatics and neural tissue on the right side of the SMA are resected with the modified en bloc resection.（Depart.of Pancreatic Surgery,Huashan Hospital（华山胰外）（华山胰外）,PDI）胰腺癌的诊治展望 寻找胰腺癌的致病因素 开发新技术早期发现胰腺癌 寻找有效药物和治疗方法 采用积极合理的综合治疗 进行多中心合作 注重和比较胰腺癌的长期或远期生存率壶 腹 部 癌