胰腺疾病-傅德良課件

1、傅 德 良胰 腺 疾 病復(fù)旦大學(xué)附屬華山醫(yī)院胰腺外科復(fù)旦大學(xué)胰腺病研究所學(xué)科負(fù)責(zé)人傅德良復(fù)旦大學(xué)外科系教授，博士生導(dǎo)師華山醫(yī)院胰腺外科 主任 復(fù)旦大學(xué)胰腺病研究所 常務(wù)副所長(zhǎng)上海市醫(yī)學(xué)領(lǐng)軍人才/上海市胰腺學(xué)科優(yōu)秀帶頭人上海醫(yī)學(xué)會(huì)外科分會(huì)胰腺學(xué)組 副組長(zhǎng)上海市抗癌協(xié)會(huì)胰腺癌專業(yè)委員會(huì) 副主任委員中國(guó)抗癌協(xié)會(huì)胰腺癌專業(yè)委員會(huì) 常委中國(guó)臨床腫瘤協(xié)會(huì)CSCO胰腺癌專家委員會(huì) 副主任委員World J Gastroenterol ( SCI )、中華肝膽外科等 編委Email: 胰腺外科-科室構(gòu)成博士生導(dǎo)師2名（博士點(diǎn)）碩士生導(dǎo)師1名（碩士點(diǎn)）教授 1主任醫(yī)師2、副教授 2高年主治 2低年主治1住院醫(yī)師

2、1低年主治1低年主治1住院醫(yī)師1住院醫(yī)師1所有主治醫(yī)師均獲博士學(xué)位所有住院醫(yī)師均獲碩士學(xué)位胰腺的臨床應(yīng)用解剖生理概要長(zhǎng)約1520 cm，寬34 cm，厚1.5 cm分頭、頸、體、尾四部主胰管（Wirsung管）與膽總管匯合方式胰腺血供、淋巴回流胰腺內(nèi)、外分泌功能Detailed Anatomy of PancreasThe distal common bile duct and main pancreatic duct may join outside the duodenal wall to form a long common channel, within the duodenal wa

3、ll to form a short common channel, or they may enter the duodenum through two distinct ostia. Anatomy- arteryThe pancreatic head is supplied by branches of the gastroduodenal and superior mesenteric arteries, whereas the body and tail are supplied by branches of the splenic artery. Anatomy -veinVeno

4、us drainage is to the splenic, superior mesenteric, and portal veins Pancreatic lymphatic drainageThe major drainage of the pancreatic head and uncinate process is to the subpyloric, portal, mesenteric, mesocolic, and aortocaval nodes. The pancreatic body and tail, for the most part, are drained thr

5、ough nodes in the celiac, aortocaval, mesenteric, and mesocolic groups and through nodes in the splenic hilum PhysiologyThe pancreas is innervated by both sympathetic and parasympathetic components of the autonomic nervous system. The principal, and possibly only, pathway for pancreatic pain involve

6、s nociceptive fibers arising in the pancreas , The nerves of the pancreas travel with the blood vessels supplying the organ. 急 性 胰 腺 炎發(fā) 病 原 因 （1）胰液排出受阻或返流 膽道疾?。耗懣偣芟露私Y(jié)石嵌頓、膽道蛔蟲癥， Oddi括約肌炎性水腫狹窄 胰管梗阻：胰管結(jié)石、腫瘤或十二指腸梗阻； 環(huán)狀胰腺、十二指腸憩室 手術(shù)創(chuàng)傷、ERCP 、 暴飲暴食 （2）胰腺組織受損 酒精中毒：胰液分泌增加，Oddi括約肌水腫梗阻， 毒性破壞 手術(shù)或外傷造成胰腺血供障礙 （3）感染

7、：腮腺炎病毒、肝炎病毒、傷寒桿菌 （4）代謝紊亂、藥物、妊娠、精神因素 （5）不明原因（特發(fā)性胰腺炎）發(fā) 病 機(jī) 理膽石癥、酒精、創(chuàng)傷、特發(fā)性防御機(jī)制破壞胰蛋 白酶 蛋白質(zhì)消化、組織壞死脂 肪 酶 脂肪分解、游離脂肪酶彈 力 酶 血管破壞出血膠 原 酶 炎癥擴(kuò)散磷 脂 酶 細(xì)胞膜破壞激 肽 釋 血管通透性增加，凝血系統(tǒng)激活 放 酶SIRS、休克、DIC、MOF、胰性腦病、死亡Pathophysiology of acute pancreatitis(schematic diagram)NormalAcute pancreatitisJean-Louis Frossard, et al. Lan

8、cet 2008; 371: 14352基本病理改變胰腺不同程度的水腫、充血、出血和壞死急性水腫性胰腺炎：胰腺腫脹、包膜緊張，其下有積液 脂肪組織可見(jiàn)黃白色的皂化斑 有淡黃色腹水急性出血壞死性胰腺炎： 胰腺實(shí)質(zhì)出血壞死，呈暗紅或黑色，分葉結(jié)構(gòu)消失 脂肪組織可見(jiàn)皂化斑和壞死灶， 腹膜后可見(jiàn)廣泛的壞死組織， 伴有咖啡色或暗紅色血性腹水 晚期胰周可見(jiàn)膿腫臨 床 表 現(xiàn) （1）持續(xù)性存在、陣發(fā)性加重的劇烈腹痛 （2）頑固性惡心嘔吐, 嘔吐后腹痛不緩解 （3）腹膜炎體征 （4）腹脹、腸麻痹、腸梗阻、腹腔積液、ACS （5）休克表現(xiàn)、體溫升高、低鈣抽搐 （6）多器官功能衰竭(MOF)、ARDS、中毒性腦病

9、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診 斷（1）胰酶測(cè)定: 血、尿淀粉酶 血脂肪酶（達(dá)1.5康氏單位）（2）腹腔穿刺：腹水淀粉酶測(cè)定（3）B超檢查：膽道病變、腹水（4）CT ：明確診斷、壞死部位、胰外侵犯程度（5）X 線：橫結(jié)腸、胃擴(kuò)張、左膈肌抬高、 胸腔積液 (6) 腹腔引流液細(xì)菌

10、培養(yǎng)腹腔感染監(jiān)測(cè)急性水腫性胰腺炎CT表現(xiàn)急性壞死性胰腺炎CT表現(xiàn)急性胰腺炎分類水腫性胰腺炎 （輕型）出血壞死性胰腺炎 （重型） （1）癥狀加重，出現(xiàn)中毒癥狀，黃疸加深 （2）WBC 16109/L、血紅蛋白和紅細(xì)胞比積下降 （3）血糖 11.1mmol/L、血鈣1.87mmol/L （4）PaO2 150 mg/L, after 48 h)serum procalcitonin (5.7 ng/mL) Classify into mild or severe acute pancreatitis ( Atlanta classification 1992)急性胰腺炎的Balthazar （CT

11、分級(jí)評(píng)分法）A級(jí) 胰腺正常 0 分B級(jí) 胰腺局限或彌漫性腫大 1 分C級(jí) B級(jí)胰周炎性改變 2 分D級(jí) 胰腺病變胰腺單發(fā)性積液區(qū) 3 分E級(jí) 胰腺或胰周2個(gè)或多個(gè)積液積氣區(qū) 4 分 壞死范圍 30，再加2分 50，再加4分 50，再加6分Acute pancreatitis CT Severity Index (CTSI)Bradley EL 3rd. A clinically based classication system for acute pancreatitis: Summary of the International Symposium on Acute Pancreatiti

12、s, 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 management of AP. Nat Clin Pract Gastroenterol Hepatol,

13、 2005;2: 473483急性胰腺炎的APACHE評(píng)分急性生理學(xué)變量 直腸肛溫、平均動(dòng)脈壓、心率、呼吸、氧合作用 (FiO2 )、pH、血清鉀、鈉、肌酐、血細(xì)胞壓積、 白細(xì)胞計(jì)數(shù)年齡因素慢性健康狀況 肝、腎、心血管、呼吸系統(tǒng)、免疫障礙Assessment Criteria of severity for acute pancreatitisRansons Prognostic Signs- Gallstone PancreatitisADMISSIONINITIAL 48 HOURSAge 70 yrHct fall 10WBC 18,000/mm3BUN elevation 2 mg/1

14、00 mLGlucose 220 mg/100 mLCa2+ 400 IU/LBase deficit 5 mEq/LAST 250U/100 mLFluid sequestration 4 LAST, 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: Prognostic signs an

15、d 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, 1982ADMISSIONINITIAL 48 HOURSAge 55 yrHct fall 10WBC 16,000/mm3BUN elevation 5 mg/100 mLGlucos

16、e 200 mg/100 mLCa2+ 350 IU/LPaO2 250U/100 mLBase deficit 4 mEq/LFluid sequestration 6 LRansons Prognostic Signs- nongallstone PancreatitisFor a diagnosis of severe acute pancreatitis in a patient with pancreatitis, three or more above criteria must be present.Ranson JHC, et al: Prognostic signs and

17、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, 1982急性胰腺炎的臨床診斷分型 分級(jí) 輕型急性胰腺炎 級(jí) 無(wú)功能障 重癥急性胰腺炎 級(jí) 有功能障礙局部并發(fā)癥 分期 胰腺及胰周組織壞死 急性反應(yīng)期（710天） 胰腺及胰周膿腫 全身感染（1月

18、左右） 急性胰腺假性囊腫 殘余感染期（1月） 胃腸道瘺形成鑒 別 診 斷急性膽囊炎 急性胃腸炎消化性潰瘍穿孔 冠心病發(fā)作急性腸梗阻 急性腎絞痛 應(yīng)用指證水腫性胰腺炎急性胰腺炎的全身反應(yīng)期尚無(wú)感染的出血壞死性胰腺炎FNA非手術(shù)治療 （1）控制飲食和胃腸減壓 （2）抗休克、糾正水電解質(zhì)紊亂 （3）抗感染，支持治療 （4）減少和抑制胰酶分泌（加貝酯、生長(zhǎng)抑素） （5）抑制炎性介質(zhì)釋放（短時(shí)超濾、烏司他啶、激素） （6）解痙止痛，中醫(yī)中藥治療（大黃、芒硝） （7）腹腔引流、灌洗：降低腹內(nèi)壓、減少毒素吸收 (8) 膽道內(nèi)支架、內(nèi)鏡鼻膽管引流或胰管引流 治 療方 法手術(shù)指證： 膽源性胰腺炎（急診ERCP引

19、流/取石） 胰腺及胰周壞死組織繼發(fā)感染 暴發(fā)性胰腺炎多器官功能障礙不能糾正 急性胰腺炎經(jīng)非手術(shù)治療而臨床癥狀惡化 不能排除其他急腹癥 疾病后期出現(xiàn)腸瘺或假性囊腫手術(shù)治療目 的： 解除病因，腹腔減壓 清除胰酶、毒性物質(zhì)和壞死組織 引流膿腫、腸瘺方 法： 清除壞死組織(規(guī)則胰腺切除) 腹腔灌洗引流 三造口（胃、空腸、膽總管） 微創(chuàng)引流（經(jīng)內(nèi)窺鏡、腹腔鏡）胰腺腫瘤Benign / malignantExocrine (acinar and ductal cell) Endocrine ( Pancreatic islet cell tumors )內(nèi)分泌腫瘤 Alpha cell Glucagon

20、GlucagonomaBeta cell Insulin InsulinomaDelta cell Somatostatin SomatostatinomaDelta-2-cells VIP WDHA (Vipoma)G-cells Gastrin ZES (Gastrinoma)胰 腺 癌胰腺癌惡性程度高，預(yù)后極差，社會(huì)影響很大胰腺癌僅占全身癌腫2%，但死亡率卻占6%Siegel R, et al. Cancer statistics( 2011). CA Cancer J Clin. 2010;61:212-236.Pancreatic cancer is the 10th most co

21、mmonly diagnosed cancer and the 4th leading cause of cancer death in the United States.Estimated numbers of cancer cases and cancerdeaths in the 40 European countries (in thousands)Ferlay J. et al. Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer,2010;46:765 781Incidence 7

22、thMortality 5thPancreatic cancer我國(guó)胰腺癌的發(fā)病率明顯上升的趨勢(shì)發(fā)病率（單位：/10萬(wàn)）中國(guó)胰腺癌的發(fā)病趨勢(shì)中華內(nèi)科雜志，2005；44（7）：509-513During 2002 to 2006, new cases : 8190 pts in ShanghaiRough incidence：Male 13.13/100000, list in the 8th ， Female: 11.21/100000, list in the 7th，Incidence of pancreatic cancer increased in Shanghai (1973200

23、6) 2006 incidence :12.16/10 /100000, Similar to incidence in US for patients 65yearsOncogenes and Tumor suppressor Genes In Pancreatic Cancer Genetic abnormalities in pancreatic cancers: activation of growth-promoting oncogenes, mutations that result in the inactivation of tumor suppressor genes, an

24、d 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.Paula Ghaneh, et al. Biology and management of p

25、ancreatic 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.Early changes include Her-2/neu and K-ras

26、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 is One of the Deadliest Cancers (Pancreatic Cancer Action Network Facts 2011)Pancreatic cancer has the highest mortality

27、 rate of all the major cancers: only 6% survive more than five 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 impr

28、oved only from 3% to 6%. It is estimated that 43,140 Americans will 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 2

29、010 and 2030).胰腺癌早期診斷困難早期癥狀隱匿，缺乏特異性醫(yī)生對(duì)胰腺癌疾病的認(rèn)識(shí)不足，對(duì)有癥狀者沒(méi)有引起足夠的重視醫(yī)院尚未具備早期胰腺癌診斷的設(shè)備和水平臨 床 特 點(diǎn)（1）惡性程度高，早期發(fā)現(xiàn)困難，預(yù)后差（2）多發(fā)生于頭部（2/3），體尾部少（1/3）（3）胰管癌占90，腺泡細(xì)胞癌較少（4）胰腺癌以淋巴轉(zhuǎn)移和局部浸潤(rùn)為主（5）胰腺癌的發(fā)病率增加，生存率低淋巴轉(zhuǎn)移胰腺癌主要轉(zhuǎn)移方式 影響手術(shù)預(yù)后的重要因素 Pawlik T M. et al, Surgery 2007;141:610-8 Isaji, Yoshifumi, et al. Pancreas, 2004; 3(28):2

30、31-23 Carr JA, et al. Am Surg, 1999; 65(12): 1143-1149 臨 床 表 現(xiàn) （1）上腹痛和上腹飽脹不適 （2）進(jìn)行性梗阻性黃疸 （3）突發(fā)的糖尿病、急性胰腺炎表現(xiàn) （4）不典型的消化道癥狀 （5）不明原因的消瘦、乏力、后背痛 （6）晚期表現(xiàn)：腫塊、腹水、發(fā)熱等原則：以病史采集為基礎(chǔ)輔以特殊實(shí)驗(yàn)室和影像學(xué)檢查手段從無(wú)創(chuàng)到有創(chuàng)定位、定性和分期診斷兼顧臨 床 診 斷胰腺癌的高危因素高危人群年齡大于40歲，有上腹部非特異性癥狀者； 有胰腺癌家族史者； 突發(fā)糖尿病患者，特別是不典型糖尿?。?慢性胰腺炎患者；導(dǎo)管內(nèi)乳頭狀粘液瘤； 家族性腺瘤息肉病； 遠(yuǎn)端胃

31、大部切除者；胰腺囊腫患者； 有惡性腫瘤高危因素者；診 斷 方 法（1）提高警惕，爭(zhēng)取早期診斷（2）血生化檢查：血尿淀粉酶、血糖、肝功能異常（3）免疫學(xué)檢查：CEA、CA50、CA19-9、PCAA、 CA125、CA724 、CA242 （4）影像學(xué)檢查：Bus、CT、ERCP（MRCP）、PTC（5）細(xì)針穿刺活檢：脫落細(xì)胞檢查、癌基因檢測(cè) （K-ras、P53）胰腺癌早期診斷的水平有待提高多排螺旋CT空間分辨率高，定位診斷良好良惡性病變的鑒別作用局限MRI/MRCP清楚顯示胰膽管結(jié)構(gòu)良惡性病變的鑒別作用局限ERCP 可進(jìn)行脫落細(xì)胞學(xué)檢查以及治療 有創(chuàng)性EUS/FNA術(shù)前取得病理，診斷靈敏度、

32、特異度高有創(chuàng)性，臨床普及難CA199等腫瘤標(biāo)志物方便，安全，適合于普查敏感性高特異性較差PET/CT功能檢測(cè)與解剖結(jié)構(gòu)檢測(cè)相融合 有助于早期診斷的正確性胰腺癌CT成像胰腺癌CT成像門靜脈期動(dòng)脈期實(shí)質(zhì)期胰頭癌的雙管征胰腺血供的CT三維重建動(dòng)脈血供三維重建門靜脈系統(tǒng)三維重建腸系膜上靜脈重建多排CTA可以更精確地顯示胰腺小病灶，進(jìn)行周圍血管的三維重建Type AType BType CType DType EType FCT criteria of vascular invasion for pancreatic cancer胰頭腫瘤的MR征像同一病例， MRI T1WI 雙期增強(qiáng)成像，動(dòng)脈期和門脈

33、期顯示癌腫實(shí)質(zhì)部分增強(qiáng)，增強(qiáng)程度與無(wú)癌胰腺相仿，壞死灶不增強(qiáng)（箭）。T1WI增強(qiáng)成像 動(dòng)脈期T1WI增強(qiáng)成像 門脈期壞死、囊變T1低信號(hào)，T2高信號(hào)，不增強(qiáng)胰頭腫瘤的MR征像T1WI 平掃M(jìn)RCPMRI GRE T1WI平掃顯示癌腫為相對(duì)低信號(hào)，信號(hào)強(qiáng)度不均勻，MRCP顯示癌腫遠(yuǎn)端（上游）胰腺導(dǎo)管和膽管突然中斷、擴(kuò)大，即雙管征（膽/胰管均突然中斷、擴(kuò)大）。雙 管 征磁共振胰膽管成像（MRCP）正常MRCP胰腺癌MRCP壺腹癌MRCPPET-CT探測(cè)18F湮滅輻射后發(fā)射的射線, 獲得18F-FDG在體內(nèi)的分布影像, 反映體內(nèi)葡萄糖代謝的狀態(tài)和水平18F-氟代脫氧葡萄糖（18F-FDG） 腫瘤顯像

34、功能學(xué)半定量檢測(cè) SUV(standard uptake value) 滯留指數(shù)(retention index, RI)BIOGRAPH 64 HD RI = (SUV延遲-SUV早期)100/SUV早期,診斷精確度達(dá)到88%; 延遲圖像可多發(fā)現(xiàn)肝轉(zhuǎn)移、淋巴結(jié)等轉(zhuǎn)移灶 The FDG is not metabolized and is trapped inside the cell allowing it to be imaged in contrast to surrounding tissuePET/CT Evaluation for pancreatic massPETCTPET/CT

35、PET/CT Evaluation for pancreatic cancerWhole scanning of PETCTPET/CT Evaluation for metastatic pancreatic cancer內(nèi)鏡超聲EUSFNA胰腺癌的定性診斷 術(shù)中活檢以明確病理診斷 B超或CT引導(dǎo)下經(jīng)皮細(xì)針穿刺 內(nèi)鏡超聲引導(dǎo)下的細(xì)針穿刺抽吸細(xì)胞學(xué)檢查（FNA） 胰腺癌UICC的TNM分期 分期腫瘤大小淋巴結(jié)轉(zhuǎn)移遠(yuǎn)處轉(zhuǎn)移0期TisN0M0期T1N0M0T2N0M0期T3N0M0期T1N1M0T2N1M0T3N1M0a期T4任何NM0b期任何T任何NM1胰腺癌診斷的JPS分期分期腫瘤大小淋巴結(jié)轉(zhuǎn)

36、移遠(yuǎn)處轉(zhuǎn)移期TlaN0M0期T1aN1M0T1bN0,N1M0期T1a ,T1bN2M0T2N0,N1M0a期 T1a ,T1bN3M0T2N2M0T3N0,N1M0b期T2N3M0T3N2,N3M0任何T任何NM1手術(shù)為主的綜合治療輔助治療 化療：介入、靜脈化療、口服化療 放療：（術(shù)中、調(diào)強(qiáng)適形、伽瑪?shù)叮?、I125短程放療新輔助治療生物靶向治療生物免疫治療中醫(yī)中藥治療支持治療胰腺癌的治療Kausch-Whipple surgical procedure for pancreatic cancer Allen O Whipple, MDPyloric-preserving WhippleSta

37、ndard Whipple Kausch W. Das Carcinom der Papilla Duodeni und seine 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胰腺癌手術(shù)治療的認(rèn)知 From:“None of us is too youngto be aware of thetimidity with whichsurgeons in generalhave approached anyradical interference onthe pancreas.”To: “Surgical resection provides the only potential cure for panc