胰腺癌胰液蛋白质组学分析

目的:利用比较蛋白质组学方法鏊定胰腺癌早期诊断的蛋白标志.方法:采用双向电泳(2-DE)分离比较9个胰腺导管腺癌患者和9个非胰腺癌患者的胰液蛋白质表达谱,用肤质量指纹图谱(PMF)为基础的基质辅助激光解析离子化飞行时间串联质谱(MALDF-TO-F-MS/MS)对差异蛋白进行鉴定.采用蛋白质印迹方法进一步验证蛋白质MMP-9和DJ-1在胰液中的表迭.结果:2-DE显示共24个蛋白质点出现>2.0倍的表达差异,上调14个,下调10个.蛋白质印迹检测显示在胰腺癌胰液中高表达MMP-9和DJ-1蛋白.结论:MMP-9和DJ-1可能成为通过内镜下逆行胰胆管造影术(ERCP)筛查胰腺癌高危患者及早期诊断胰腺癌的潜在的胰液肿瘤标志.     

胰液端粒酶活性检测在胰腺疾病鉴别诊断中的价值

目的 :探讨端粒酶活性推测在胰腺癌早期诊断中的价值。方法 :4 0例胰腺癌和 31例慢性胰腺炎患者均行ERCP抽取胰液 ,采用TRAP PCR SSCP和TRAP PCR ELISA两种方法分别进行定性、定量分析 ,同时检测胰腺癌细胞株 4株 ,正常胰液和正常胰腺组织测定其端粒酶活性做为对照。结果 :端粒酶定性分析 :胰腺癌组胰液中阳性率 67 5 0 % ( 2 7/40 ) ;慢性胰腺炎组 4 1 93% ( 13/31) ;胰腺癌细胞株全部为阳性 ,阳性率 10 0 % ( 4 /4) ;正常胰腺和胰腺组织均呈阴性 ( 0 /5 )。端粒酶定量测定 :胰腺癌组为1 4 75± 0 4 67;慢性胰腺炎组为 0 35 8± 0 4 79。胰腺癌细胞株为 1 84 2± 0 2 5 6。胰腺癌组胰液中端粒酶阳性率明显高于慢性胰腺炎组 ,P <0 0 5 ;胰腺癌患者组 ,高于慢性胰腺炎组 ,P <0 0 1。结论 :胰液中端粒酶活性测定可作为胰腺良恶性疾病鉴别诊断的重要依据 ,可作为胰腺癌早期诊断的手段之一     

胰、脾（081449～081457）

NF-kB反义核酸对胰腺癌细胞ICAM-1表达及侵袭力的影响；人胰腺癌胰液蛋白质差异表达分析；胰腺癌组织乙酰肝素酶表达及其与肿瘤血管形成及预后关系的研究；淋巴结转移及肿瘤病理学特点对胰头癌预后的影响；胰十二指肠切除改良胰管空肠吻合预防胰瘘     

胰腺癌患者行内镜逆行胰胆管造影术放置胰管支架后发生胰腺炎的危险因素分析

目的:确定胰腺癌患者行内镜逆行胰胆管造影术放置胰管支架后发生胰腺炎的危险因素。方法:收集2016年4月至2018年7月62名初次接受内镜逆行胰胆管造影术,并在术中插入了胰腺支架预防术后急性胰腺炎的胰腺癌患者的资料。其中术后发生急性胰腺炎患者24例,未发生胰腺炎患者38例,采用固定回归和随机效应的Logistic回归模型对ERCP术放置胰管支架后发生胰腺炎患者进行建模。结果:Logistic回归显示年轻、女性、高血压、插管时间超过60 min、胰管支架放置于胰头、插管次数为ERCP术放置胰管支架后发生胰腺炎的危险因素。高血压、插管时间超过60 min、胰管支架放置于胰头为其独立危险因素。结论:高血压,插管时间过长和胰管支架放置在胰头部位,决定了胰腺癌患者行内镜逆行胰胆管造影术放置胰管支架后更容易发生胰腺炎。     

胰液K-ras12密码子点突变及血清CA19-9水平与胰腺癌复发关系

背景与目的：K-ras基因是与胰腺癌相关的基因，血清CA19-9对诊断胰腺癌有价值：本工作研究目的在于探讨胰液中K-ras12密码子点突变联合血清CA19-9检测与胰腺癌病程的关系。方法：测定32例临床及手术证实的胰腺癌患者血清CA19-9水平，并采用内镜ERCP从胰管收集的胰液标本，聚合酶链反应一限制性片断长度多态性分析（PCR-PFLP）检测胰液K-ras基因12密码子点突变，分析K-ras12密吗子点突变及血清CA19-9水平联合检测与胰腺癌术后复发的关系。结果：①胰液中K-ras12密码子点突变率为56．3％，与肿瘤大小密切相关（P〈0．05）。K-ras12密码子点突变阳性、阴性表达病例3年复发率分别为66．7%和33．3％：②高血清CA19-9水平且K-ras12密码子点突变阳性组3年复发率为69．2％，而低血清CA19-9水平且K-ras12密码子点突变阳性组3年复发率为20．0％，差异具有显著性（P〈0．05）。结论：联合胰液中K-ras12密码子点突变和血清CA19-9检测可作为判断胰腺痛术后复发的有效指标，多因素分析对胰腺癌术后复发的判断更有价值。     

胰液中CLDN5和NPTX2基因高甲基化在胰腺癌诊断中的意义

目的：探讨胰腺癌和慢性胰腺炎患者胰液中CLDN5和NPTX2基因高甲基化在胰腺癌诊断中的临床意义。方法：MSP方法检测21例胰腺癌和8例慢性胰腺炎患者胰液中CLDN5和NPTX2基因启动子区CpG岛高甲基化。结果：21例胰腺癌患者的胰液中,17例（81.0%）CLDN5基因高甲基化阳性;15例（71.4%）NPTX2基因高甲基化阳性。8例慢性胰腺炎患者的胰液中,各有1例（12.5%）CLDN5和NPTX2基因高甲基化阳性。结论：CLDN5和NPTX2基因高甲基化作为分子生物学标志物可用于胰腺癌的诊断,有较高的临床应用价值。     

胰腺导管癌神经生长因子mRNA表达及意义

目的研究胰腺导管癌和慢性胰腺炎组织中神经生长因子(NGF mRNA)的表达及临床病理意义.方法 51例胰腺癌和10例慢性胰腺炎手术切除标本经40 g/L中性甲醛固定后常规制作石蜡包埋切片,NGF mRNA染色为原位杂交法.结果胰腺癌组织NGF mRNA阳性率(54.9%)明显高于慢性胰腺炎(10.0%),差异有高度显著性(χ2=6.76,P＜0.01);高分化腺癌、未转移胰腺癌NGF mRNA表达阳性率明显低于低分化腺癌(25.0%对84.2%;χ2=13.74,P＜0.01)和转移病例(31.3%对65.7%;χ2=5.27,P＜0.05), NGF mRNA与胰腺癌其他临床病理特征无明显相关.结论 NGF mRNA表达可能与胰腺癌发生、进展、转移及预后有较密切的关系,可能是胰腺癌发生、发展及预后的重要生物学标记物.     

ERCP对胰腺癌合并慢性胰腺炎的鉴别作用

本文评价了内窥镜逆行胆管造影(ERCP)对胰腺癌(PCA)合并慢性胰腺炎(CP)的诊断价值。1981年1月至1988年12月确诊为 CP 的55例中,10例(18.2%)系胰头胰癌合并 CP 患者。为确定 ERCP 鉴别 CP 及 PCA 的参数。将病人分2组,CP 组45例,为单纯性慢性胰腺炎患者;PCA 组10例,系胰腺癌合并慢性胰腺炎患者。     

胰腺癌梗阻性黄疸患者经皮穿刺胆管引流术后发生胰腺炎的危险因素分析

目的 探讨胰腺癌梗阻性黄疸患者经皮穿刺胆管引流术(PTBD)后发生胰腺炎的危险因素。方法 选取行PTBD治疗的135例胰腺癌梗阻性黄疸患者。记录术后胰腺炎发生率，并分析胰腺炎发生的危险因素。结果 135例胰腺癌梗阻性黄疸患者PTBD后发生胰腺炎的共有62例，发生率为45.93%(62/135)。单因素分析显示：年龄、性别、血红蛋白水平、合并糖尿病与胰腺癌梗阻性黄疸患者PTBD后胰腺炎的发生无关(P>0.05);而体质量指数(BMI)、通过胆管梗阻段困难、胰管显影、鼻胆管引流、引流方式与胰腺癌梗阻性黄疸患者PTBD后胰腺炎的发生相关(P<0.05);多因素Logistic回归分析显示：BMI≥28 kg/m²、通过胆管梗阻段困难、胰管显影、内外引流、鼻胆管引流是胰腺癌梗阻性黄疸患者PTBD后发生胰腺炎的主要危险因素(P<0.05)。结论 胰腺癌梗阻性黄疸患者经PTBD治疗后发生胰腺炎的风险较高，而BMI≥28 kg/m²、通过胆管梗阻段困难、胰管显影、鼻胆管引流、内外引流是术后胰腺炎发生的主要影响因素，临床需予以重视，并施行个...     

PCR—SSP鉴别慢性胰腺炎和胰腺癌

采用检测Ｋ－ｒａｓ基因第１２位密码子点突变方式（ＣＧＴ、ＧＴＴ、ＧＡＴ）设计的顺序特异性引物（ＳＳＰ）、对胰腺癌及慢性胰腺炎的冰冻组织和胰液ＰＣＲ扩增，产物借助常规电泳及染色判断有无Ｋ－基因突变及突变方式。结果：胰腺癌组织及胰液Ｋ－ｒａｓ基因突变率分别为９５．１％、９４．１％，而慢性胰腺炎组织（２９例）胰液（１７例）及正常胰腺组织（１２例）、胰液（４例）均无Ｋ－ｒａｓ基因突变。研究表明：ＰＣＲ－Ｓ     

Clinical Efficacy of Endoscopic Pancreatic Drainage for Pain Relief with Malignant Pancreatic Duct Obstruction

Objective: This study was conducted to investigate the efficacy of pancreatic drainage for pain relief in advanced pancreatic cancer. Method: Seventy-one patients with pancreatic carcinoma were divided into two groups: dilated and non-dilated pancreatic ducts. All patients underwent endoscopic retrograde cholangiopancreatography (ERCP), endoscopic biliary stenting and pancreatic stenting. Visual Analog Scale (VAS) scores, pain remission rates and survival time were evaluated during follow-up. Results: The post-ERCP VAS score of the dilated group was lower than that of the non-dilated group at 1 and 3 months post-ERCP. There was no difference at 6 months. The pain remission rate in the dilated duct group was significantly higher than that in non-dilated duct groupin 1 and 3 months post-ERCP. The median survival times were 8.17 and 8.22 months respectively. Conclusion: Endoscopic pancreatic drainage can relieve pain of advanced pancreatic cancer accompanied by safe dilation of the pancreatic duct.     

Role of the preoperative usefulness of the pathological diagnosis of pancreatic diseases

Pancreatic cancer is the fifth leading cause of cancer death and has the lowest survival rate of any solid cancer. Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA) is currently capable of providing a cytopathological diagnosis of pancreatic malignancies with a higher diagnostic power, with a sensitivity and specificity of 85%-89% and 98%-99%, compared to pancreatic juice cytology (PJC), whose sensitivity and specificity are only 33.3%-93% and 83.3%-100%. However, EUS-FNA is not effective in the cases of carcinoma in situ and minimally invasive carcinoma because both are undetectable by endoscopic ultrasonography, although PJC is able to detect them. As for the frequency of complications such as post endoscopic retrograde cholangiopancreatography pancreatitis, EUS-FNA is safer than PJC. To diagnose pancreatic cancer appropriately, it is necessary for us to master both procedures so that we can select the best methods of sampling tissues while considering the patient’s safety and condition.     

Two‐tone pancreas on T1‐weighted images: Correlation with abnormalities on magnetic resonance pancreatography

Two patients are presented in whom geographical alteration in signal between areas of normal and abnormal pancreatic tissue on T1‐weighted magnetic resonance images of the pancreas was observed. This alteration in signal intensity produced a ‘two‐tone’ pattern; magnetic resonance cholangiopancreatography (MRCP) and endoscopic retrograde cholangiopancreatography (ERCP) in both patients revealed altered pancreatic duct drainage. It is believed that the ‘two‐tone’ pancreas effect on T1‐weighted images of the abdomen, may indicate aberrant duct drainage and that MRCP is an ideal means of further evaluation.     

Imaging of the normal and abnormal pancreatico-biliary system with single-shot MR cholangiopancreatography: A pictorial review

Magnetic resonance cholangiopancreatography (MRCP) is a rapidly evolving non-invasive imaging modality that produces images of the pancreatic duct and biliary tree without the need for intravenous or oral contrast. The images are equivalent to those from endoscopic retrograde cholangiopancreatography (ERCP), but the non-invasive acquisition avoids the morbidity and mortality associated with diagnostic ERCP. Magnetic resonance cholangiopancreatography is indicated in patients who require only a diagnostic ERCP, who fail an ERCP or who are unable to undergo ERCP due to altered post-surgical anatomy. Other evolving indications include triaging of patients with obstructive jaundice into percutaneous or endoscopic management drainage pathways depending on the site, length and nature of the duct obstruction, thereby potentially decreasing the number of failed or unsuccessful ERCP. Pre-operative identification of anomalous biliary anatomy and choledocholithiasis prior to laparoscopic cholecystectomy promise to modify the pre-operative and operative management of the patient in order to minimize the risk of duct injury and unnecessary intra-operative dissection and cholangiography. The advantages of the technique include its non-invasiveness, the absence of contrast administration, its relative operator independence and the ability to evaluate both sides of an obstructed duct, thereby accurately evaluating stricture morphology and length. The disadvantages of MRCP compared to ERCP include its lack of an immediate therapeutic solution to duct obstruction, procedural cost, unit availability and the inability to evaluate patients with pacemakers or ferromagnetic implants.     

Diagnosis of exocrine diseases of the pancreas: is there still a role for endoscopic retrograde cholangiopancreatography (ERCP)?

In the diagnosis of exocrine diseases of the pancreas, three major questions should be addressed: when only MR cholangiopancreatography should be applied; when endoscopic retrograde cholangiopancreatography should be applied directly; when a combined approach should be applied. In pancreatic disease MRI has many indications because ultrasonography, the procedure of choice, is rarely able to resolve the diagnostic problem, with a clearcut indication for therapeutic endoscopic retrograde cholangiopancreatography. One of the rare cases where MRI could be omitted is represented by pancreatic cancer with biliary obstruction in non operable patients in whom a pancreatic mass was already visualized on ultrasonography. In all other diseases of the pancreas, the combination of MRI/MRCP with secretin stimulation and ERCP usually favors the first procedure, preventing a number of diagnostic ERCP.     

Cytologic examination of pure pancreatic juice in the diagnosis of pancreatic carcinoma. The endoscopic retrograde intraductal catheter aspiration cytologic technique.

BACKGROUND. Although cytologic examination of pure pancreatic juice obtained with a duodenofiberscope has been useful for the diagnosis of pancreatic carcinoma, the rate of false-negative results is reported to be high. To eliminate these false-negative results, the authors developed a new technique, endoscopic retrograde intraductal catheter aspiration cytology, especially for an accurate cytologic diagnosis of carcinoma of the body or tail of the pancreas. METHODS. The accuracy of conventional cytologic examination of pure pancreatic juice was assessed in 25 patients with pancreatic carcinoma, 29 patients with pancreatitis, and 52 control subjects. Pure pancreatic juice was collected from the pancreatic duct by endoscopic cannulation using a videoimaging duodenoscope after intravenous administration of secretin. The new endoscopic retrograde intraductal catheter aspiration technique was used in four patients with carcinoma of the body or tail of the pancreas and five patients with localized pancreatitis in whom a correct diagnosis was not made by previous cytologic examination of pure pancreatic juice. RESULTS. Positive cytologic findings were obtained in 76% of the patients with pancreatic carcinoma. Positive cytologic results were more frequent in patients with carcinoma of the head of the pancreas than in those with carcinoma of the body or tail. By the new technique, positive cytologic results were obtained in all of the patients with pancreatic carcinoma. This technique caused no severe complications. CONCLUSIONS. This procedure of endoscopic retrograde intraductal catheter aspiration cytology seems useful for diagnosis of pancreatic carcinoma.     

Endoscopic Retrograde Cholangiopancreatography: The Diagnosis of Hepatobiliary and Pancreatic Carcinoma

In a consecutive series of 68 patients subjected to endoscopic retrograde cholangiopancreatography (E.R.C.P.), 17 proved to have hepatobiliary or pancreatic malignancy. In 14 of the 17 patients (82%) the diagnosis of malignancy was established at E.R.C.P., and in a further case malignancy was suspected. Malignancies found were carcinoma of the pancreas (11), periampullary carcinoma of the pancreas (1), cholangiocarcinoma (2) and secondary carcinoma in the pancreas (1). The two patients whose tumours were not diagnosed at E.R.C.P. were subsequently found to have hepatomas. In 5 instances, the diagnosis of tumour was made by endoscopy and biopsy alone; in the other 10 cases, diagnosis depended on the radiological features. The 7 pancreatic malignancies showed stenosis (3) or obstruction (4) of the pancreatic duct, and in 4 cases there was an associated abnormality on the cholangiogram. The 2 cholangiocarcinomas had strictures (2)     

Role of endoscopic ultrasound in the diagnosis of pancreatic cancer

Endoscopic ultrasonography (EUS) with or without fine needle aspiration has become the main technique for evaluating pancreatobiliary disorders and has proved to have a higher diagnostic yield than positron emission tomography, computed tomography (CT) and transabdominal ultrasound for recognising early pancreatic tumors. As a diagnostic modality for pancreatic cancer, EUS has proved rates higher than 90%, especially for lesions less than 2-3 cm in size in which it reaches a sensitivity rate of 99% vs 55% for CT. Besides, EUS has a very high negative predictive value and thus EUS can reliably exclude pancreatic cancer. The complication rate of EUS is as low as 1.1%-3.0%. New technical developments such as elastography and the use of contrast agents have recently been applied to EUS, improving its diagnostic capability. EUS has been found to be superior to the recent multidetector CT for T staging with less risk of overstaying in comparison to both CT and magnetic resonance imaging, so that patients are not being ruled out of a potentially beneficial resection. The accuracy for N staging with EUS is 64%-82%. In unresectable cancers, EUS also plays a therapeutic role by means of treating oncological pain through celiac plexus block, biliary drainage in obstructive jaundice in patients where endoscopic retrograde cholangiopancreatography is not affordable and aiding radiotherapy and chemotherapy.     

Identification of K-ras Oncogene Mutations in the Pure Pancreatic Juice of Patients with Ductal Pancreatic Cancers

Pancreatic cancer is detected on the basis of morphological changes delineated by means of various image-diagnostic methods. However, differentiation between chronic pancreatitis and pancreatic cancer, especially at the early stage, is not always simple when based upon the morphological changes alone. Therefore, we attempted to elucidate K- ras mutations in the sediment of pure pancreatic juice (PPJ) containing exfoliated ductal pancreatic cancer cells. PPJ was collected endoscopically from 20 patients with pancreatic cancer (PC) and 18 patients with chronic pancreatitis (CP). Polymerase chain reaction and allele specific oligonucleotide dot blot hybridization for K- ras mutations were performed with the DNA extracted from these samples. A K- ras mutation at codon 12 was identified in the PPJ of 11/20 (55%) of the patients with PC. On the other hand, the same mutation was not identified in the PPJ of any patient with CP. Moreover, K- ras mutations at codons 13 and 61 were not recognized in the PPJ of any patient with either PC or CP. These findings suggested that the presence of a K- ras mutation at codon 12 in PPJ would be useful in confirming the diagnosis of PC.