胰腺癌的早期诊断

胰腺癌的早期症状和体征多无特异性,现有的辅助检查及肿瘤标志物并未能使胰腺癌的早期诊断率大幅度提高。复习相关资料,就流行病学,影像学和肿瘤标志物三方面来评价目前胰腺癌早期诊断的现状及进展作一综述。     

Clinical significance of extrahepatic bile duct resection for advanced gallbladder cancer

BACKGROUND AND OBJECTIVES: The aim of this study was to determine the clinical significance of extrahepatic bile duct (EHBD) resection during surgery for advanced gallbladder cancer. METHODS: Among 110 patients with pT2 or higher grade gallbladder cancer, 58 patients without microscopic invasion to the EHBD were reviewed. Prognostic factors of the 58 patients were evaluated by multivariate analysis. The impact of EHBD resection on survival was assessed in relation to two prognostic determinants: (i) lymph node metastasis: positive (n = 23) and negative (n = 35); (ii) perineural invasion: positive (n = 25) and negative (n = 33). RESULTS: Hepatic metastasis and perineural invasion were found to be independently significant prognostic factors. (i) No survival benefit of additional EHBD resection could be confirmed in each group of patients with or without nodal metastasis. (ii) In 25 patients with perineural invasion, 14 patients who underwent EHBD resection showed better survival as compared to the 11 patients who did not undergo EHBD resection (5-year survival rate, 46% vs. 0%, P = 0.009). In the remaining 33 patients without perineural invasion, the additional EHBD resection did not yield significant improvement of survival (P = 0.28). CONCLUSIONS: Resection of EHBD may offer prognostic advantage when perineural invasion exists, even in the absence of biliary infiltration.     

Radiotherapy with multiple fractions per day in pancreatic and bile duct cancer

Twenty patients with pancreatic and bile duct cancer have been treated with external radiotherapy with multiple fractions per day (MFD). All patients had localized disease only. Sixteen patients have been treated with a split-course technique, to a dose of 60 to 70 Gy in 7-8 weeks, four patients had a continuous series of 44 Gy in 19 days. The mean survival was 7.9 months for patients with a pancreatic cancer. Four out of nine patients with pancreatic cancer in whom the tumour was evaluable showed a tumour regression, one out of nine reached a partial remission. The mean survival in the responders was 9.5 months. All patients with pancreatic cancer died of their tumour. Four out of eight patients with bile duct cancer died of their tumour, the mean survival was 10 months. Four patients with bile duct cancer are still alive (10+, 10+, 10+, 11+ months). No serious acute toxicity was seen. Six patients showed gastrointestinal toxicity at 1.5 to 9 months after the end of treatment. All of them could be treated in a conservative way. From the results obtained in this feasibility study, radiotherapy with MFD in pancreatic and bile duct cancer appears to achieve similar tumour response as conventionally fractionated radiotherapy and the observed toxicity of MFD can be considered as acceptable. MFD might be a more appropriate treatment scheme for combination with chemotherapy and radiosensitizers.     

Imaging diagnosis of bile duct cystadenocarcinoma

Two patients with surgically resected biliary cystadenocarcinoma are presented. Both were asymptomatic and the cancer was incidentally found by ultrasonography (US). In the first case, a huge multilocular tumor (21 X 15 cm in diameter) having many papillary projections and septa within it and small daughter lesions occupied both the right anterior and left medial areas of the liver. They were clearly demonstrated on US and computed tomography (CT). Angiography disclosed tumor vessels in some area of the lesion, these features strongly suggested cystadenocarcinoma. The second case had a solid mass (7 X 7 cm) in the left hepatic lobe, in which many septal structures within the lesion were seen on enhanced CT and light dot like stains were recognized on angiography. The former findings coincided with the internal gross feature of the resected specimen. Both patients are doing well 8 months and 1 year and 6 months after operation, respectively.     

CT扫描诊断直肠癌术后局部复发

本院1987年以来 CT 扫描诊断为直肠癌术后盆腔内复发23例,吻合口复发8例,其中经手术与病理学诊断证实29例复发。CT 确诊率为93.5%,检出肿瘤大小2～8 cm,其中6例无复发临床表现。CT 所见:(1)骶前区单发分叶状或结节状肿块,或多发性肿块。(2)新直肠腔不规则偏心肿块或肠腔狭窄。(3)肿瘤侵及膀胱、卵巢、前列腺、骶尾骨、精囊或盆壁肌肉的征象。CT 是当前诊断盆腔内复发的较敏感、准确的工具。     

胆管癌组织及胆汁中端粒酶活性的检测及意义

目的：检测胆管癌组织和胆汁中的端粒酶活性，以研究与端粒酶与胆管癌的关系及对胆管癌的诊断意义。方法：用PCR—ELISA方法检测20例胆管癌的癌组织和胆汁中端粒酶活性，同时用相同的方法检测20例正常胆管组织和胆汁中的端粒酶活性以作对照。结果：20例胆管癌组织中，端粒酶活性阳性为80％（16／20），胆汁中端粒酶活性阳性率75％（15／20）。正常胆管组织端粒酶活性阳性表达率为0（0／20），胆汁中端粒酶活性阳性率为0（0／20）。结论：端粒酶可能参与了胆管癌的发生发展过程，检测胆汁中端粒酶活性可有助于胆管癌的诊断。     

原发性肝癌并胆栓的诊治体会——附12例分析

目的　提出外科手术治疗原发性肝癌合并胆管癌栓的方法。方法　全组病例肝癌切除后 ,自肝断面胆管残端清除癌栓 ,胆总管切开取出癌栓。结果　随访 6～ 12个月 ,健在 7例 ,死亡 3例。结论　肝癌切除加胆管癌栓清除术对伴发胆管癌栓的原发性肝癌是一种积极有效的方法。     

胆总管下端结石合并胆总管下端癌的临床诊断及治疗

目的:研究胆总管下端结石合并胆总管下端癌的临床特点及诊治要点。方法:回顾性分析2005年1月-2012年1月间入院诊治的35例胆总管下端结石合并胆总管下端癌的临床资料,统计患者年龄与胆石症病史数据。并选取同期入院诊治的单纯胆管下端癌患者35例为对照A组,单纯胆总管下端结石的患者35例作为对照B组。对比三组患者血清肿瘤标记物水平。结果:35例胆管下端癌患者均经诊断证实存在胆管结石。所有患者术前均经B超检查,明确诊断者15例,阳性率为42.86%;24例经CT检查,确诊18例,阳性率为75.00%;30例行MRCP检查,确诊11例,阳性率为36.67%;14例行ERCP检查,确诊14例,阳性率为100.00%。实验组CA-50为(142.95±46.92)U/L,CA-199为(208.80±116.64)U/L,CEA为(18.40±3.59)μg/L;对照A组CA-50为(210.44±67.59)U/L,CA-199为(611.83±389.52)U/L,CEA为(47.41±20.97)μg/L;对照B组CA-50为(15.17±3.06)U/L,CA-199为(17.33±4.15)U/L,CEA为(7.69±3.85)μg/L。三组差异显著(P<0.05)。胆总管下端结石合并胆总管下端癌患者的年龄多为60~69岁,胆石症病史以9~13年的为多,10年以上胆石症病史的发病率高于10年以下病史者。结论:长期胆管结石病史、老年胆管结石患者,血清肿瘤因子CA-50、CA-199、CEA显著升高的患者,应高度警惕胆管癌。B超的诊断阳性率较低,可结合多种影像学诊断方法共同诊断。     

Safety of biliary stent placement followed by definitive chemoradiotherapy in patients with pancreatic cancer with bile duct obstruction

BackgroundAlthough patients with malignant bile duct obstruction due to pancreatic cancer are often initially treated with biliary stent placement, concurrent chemoradiotherapy with stents poses a potential risk of increased toxicity. This retrospective study aimed to evaluate the safety of biliary stent placement followed by definitive concurrent chemoradiotherapy in patients with pancreatic cancer.MethodsPatients with pancreatic cancer who underwent either a plastic stent or a self-expanding metallic stent placement for malignant bile duct obstruction before definitive concurrent chemoradiotherapy were retrospectively reviewed. Radiotherapy was delivered in 1.8 Gy per fraction to a total dose of 50.4 Gy. Gemcitabine, TS-1 plus Gemcitabine, or TS-1 was the concurrent chemotherapy/regimen. The primary endpoint was the rate of biliary stent-related toxicities, defined as biliary bleeding, duodenal perforation, or bile duct perforation.ResultsThirty patients were included. Plastic stents were placed in 23 patients and self-expanding metallic stent in seven patients at the start of irradiation. The median follow-up time was 20 (range, 2–63) months, and 27 patients (90%) completed concurrent chemoradiotherapy. Biliary stent-related toxicity (grade 3 biliary bleeding) was confirmed in one patient (3%) with a plastic stent 9 months after concurrent chemoradiotherapy. The median duration of locoregional control, progression-free survival, and overall survival were 31.1, 7.3, and 10.5 months, respectively.ConclusionsStent placement followed by concurrent chemoradiotherapy was not associated with an apparent increase in toxicity and may be an appropriate treatment for patients with locally advanced pancreatic head cancer with bile duct obstruction.     

胰腺癌的早期诊断

胰腺癌是一种恶性程度高、预后较差的消化系统肿瘤。如果胰腺癌患者早期能够得到外科治疗,其生存状况将会明显改善。早期发现、早期诊断和早期治疗是提高存活率的关键。人们一直在努力寻找早期诊断胰腺癌的标记物如肿瘤血清学标记物、基因标记物,其中血清学标记物中有MUC基因、CA199、CA242和PSGF、CAM17．1;基因诊断标记物有癌基因、抑癌基因和端粒酶。同时影像学的发展也在早期诊断胰腺癌方面发挥了一定作用。     

胰腺癌的早期诊断

胰腙癌是一种恶性程度高、预后较差的消化系统肿瘤。如果胰腙癌患者早期能够得到外科治疗，其生存状况将会明显改善。早期发现、早期诊断和早期治疗是提高存活率的关键。人们一直在努力寻找早期诊断胰腺癌的标记物如肿瘤血清学标记物、基因标记物，其中血清学标记物中有MUC基因、CA199、CA242和TSGF、CAM17．1；基因诊断标记物有癌基因、抑癌基因和端粒酶。同时影像学的发展也在早期诊断胰腺癌方面发挥了一定作用。     

Early diagnosis of pancreatic cancer: re-evaluation of endoscopic retrograde cholangiopancreatography

Of the 215 pancreatic ductal cancer patients for these 13 years, 154 cases undergoing ERCP were analysed. ERPs of the pancreatic cancers were classified into 4 types. 1) stenosis of the main pancreatic duct (M.P. D.) 2) obstruction of the M.P.D. 3) dilatation of the M.P.D. 4) abnormal pancreatic field (normal caliber of the M.P.D.) Most of the pancreatic cancers belonged to type 1) or 2). 7 cases were small pancreatic cancers less than 2 cm in diameter. Its pancreatograms showed type 1) or 2) and almost the same as the advanced ones. So it was easy to detect these types even in early stage. But there were a few small pancreatic cancers of which the pancreatogram showed type 4), and these cases were difficult to detect by other imaging modalities (U.S. or C.T.). Even these were easy to detect by ERCP. ERCP is the most potent diagnostic modality for an early pancreatic cancers.     

18F-FDG PET/CT显像在胰腺癌诊断中的价值

目的 探讨18F-FDG PET/CT显像诊断胰腺癌中的临床价值.方法 回顾性分析我院近5年18F-FDG PET/CT显像发现胰腺肿块并行手术治疗的病例87例,将PET/CT显像的诊断结果与术后病理对照,探究18F-FDG PET/CT显像诊断胰腺癌的准确率、敏感性及特异性.结果 所有18F-FDG PET/CT显像发现胰腺肿块的病例中,18F-FDGPET/CT显像诊断为胰腺癌76例,其中术后病理结果为胰腺癌72例,胰腺滤泡型树突状细胞肉瘤1例,胰腺局限性炎症2例,胰岛素瘤1例:18F-FDG PET/CT诊断为良性肿瘤11例,其中术后病理证实胰岛素瘤5例,实质性假乳头状瘤2例,囊腺瘤2例,胰腺粘液腺癌2例.18F-FDG PET/CT显像对胰腺癌诊断的准确率为93.10％,敏感性为97.30％,特异性为69.23％.结论 18F-FDGPET/CT显像对胰腺癌诊断有较高的准确率,优于CT检查,具有重要的临床价值.     

Early diagnosis of pancreatobiliary duct malignancies by brush cytology and biopsy

Two hundred and five preoperative intraductal samplings (brushing and biopsy) were evaluated from 113 patients with biliary or Wirsung duct strictures. One hundred and three strictures could be specified by histology of the operative specimens, autopsy, or by the patients’ clinical course. Preoperative diagnostic efficacy depended on the tumor location (it was the best for ampullary and parapapillary tumors), but the average quantitative indices for sensitivity, absolute sensitivity, specificity, positive and negative predictive values, diagnostic accuracy of cytology were 53%, 20%, 100%, 100%, 25%, 59%, respectively. The same values for biopsy were 43%, 34%, 100%, 100%, 36% and 56%. These figures improved after simultaneous cytology and biopsy. Close cooperation with the endoscopist was necessary in cases of negative, inconclusive and dysplastic (27%) samples. Repetition of sampling improved the results by 8%. Among the 26 preoperative false negative cases, sampling-, technical- and interpretative errors occurred in 84%, 4% and 12%, respectively. Revision of samples revealed 4 malignant cases among the false negative cytologic brushings. Reclassification of specimens considering the latest criteria-primary and secondary malignant features, pancreatic intraepithelial neoplasia (PanINs), etc. - resulted in improvement of the diagnostic efficiency.     

Early diagnosis of pancreatic cancer: neutrophil gelatinase-associated lipocalin as a marker of pancreatic intraepithelial neoplasia

Pancreatic cancer is a highly lethal malignancy with a dismal 5-year survival of less than 5%. The scarcity of early biomarkers has considerably hindered our ability to launch preventive measures for this malignancy in a timely manner. Neutrophil gelatinase-associated lipocalin (NGAL), a 24-kDa glycoprotein, was reported to be upregulated nearly 27-fold in pancreatic cancer cells compared to normal ductal cells in a microarray analysis. Given the need for biomarkers in the early diagnosis of pancreatic cancer, we investigated the expression of NGAL in tissues with the objective of examining if NGAL immunostaining could be used to identify foci of pancreatic intraepithelial neoplasia, premalignant lesions preceding invasive cancer. To examine a possible correlation between NGAL expression and the degree of differentiation, we also analysed NGAL levels in pancreatic cancer cell lines with varying grades of differentiation. Although NGAL expression was strongly upregulated in pancreatic cancer, and moderately in pancreatitis, only a weak expression could be detected in the healthy pancreas. The average composite score for adenocarcinoma (4.26+/-2.44) was significantly higher than that for the normal pancreas (1.0) or pancreatitis (1.0) (P<0.0001). Further, although both well- and moderately differentiated pancreatic cancer were positive for NGAL, poorly differentiated adenocarcinoma was uniformly negative. Importantly, NGAL expression was detected as early as the PanIN-1 stage, suggesting that it could be a marker of the earliest premalignant changes in the pancreas. Further, we examined NGAL levels in serum samples. Serum NGAL levels were above the cutoff for healthy individuals in 94% of pancreatic cancer and 62.5% each of acute and chronic pancreatitis samples. However, the difference between NGAL levels in pancreatitis and pancreatic cancer was not significant. A ROC curve analysis revealed that ELISA for NGAL is fairly accurate in distinguishing pancreatic cancer from non-cancer cases (area under curve=0.75). In conclusion, NGAL is highly expressed in early dysplastic lesions in the pancreas, suggesting a possible role as an early diagnostic marker for pancreatic cancer. Further, serum NGAL measurement could be investigated as a possible biomarker in pancreatitis and pancreatic adenocarcinoma.     

Early detection of pancreatic cancer

Pancreatic adenocarcinoma is a low-incident but highly mortal disease. It accounts for only 3% of estimated new cancer cases each year but is currently the fourth common cause of cancer mortality. By 2030, it is expected to be the 2^nd leading cause of cancer death. There is a clear need to diagnose and classify pancreatic cancer at earlier stages in order to give patients the best chance at a definitive cure through surgery. Three precursor lesions that distinctly lead to pancreatic adenocarcinoma have been identified, and we have increasing understanding the non-genetic and genetic risk factors for the disease. With increased understanding about the risk factors, the familial patters, and associated accumulation of genetic mutations involved in pancreatic cancer, we know that there are mutations that occur early in the development of pancreatic cancer and that improved genetic risk-based strategies in screening for pancreatic cancer may be possible and successful at saving or prolonging lives. The remaining challenge is that current standards for diagnosing pancreatic cancer remain too invasive and too costly for widespread screening for pancreatic cancer. Furthermore, the promises of noninvasive methods of detection such as blood, saliva, and stool remain underdeveloped or lack robust testing. However, significant progress has been made, and we are drawing closer to a strategy for the screening and early detection of pancreatic cancer.