Efficacy of endoscopic ultrasonography and endoscopic ultrasonography-guided fine-needle aspiration for the diagnosis and grading of pancreatic neuroendocrine tumors

Background and aim: Pancreatic neuroendocrine tumors (pNETs) are histologically categorized according to the WHO 2010 classification by their mitotic index or Ki-67 index as G1, G2, or G3. The present study examined the efficacy of endoscopic ultrasonography (EUS) and EUS-guided fine-needle aspiration (EUS-FNA) in the diagnosis and grading of pNET. Methods: We retrospectively reviewed 61 pNETs in 51 patients who underwent EUS between January 2007 and June 2014. All lesions were pathologically diagnosed by surgical resection or EUS-FNA. We evaluated the detection rates of EUS for pNET and sensitivity of EUS-FNA, and compared the Ki-67 index between EUS-FNA samples and surgical specimens. EUS findings were compared between G1 and G2/G3 tumors. Results: EUS showed significantly higher sensitivity (96.7%) for identifying pNET than CT (85.2%), MRI (70.2%), and ultrasonography (75.5%). The sensitivity of EUS-FNA for the diagnosis of pNET was 89.2%. The concordance rate of WHO classification between EUS-FNA and surgical specimens was 69.2% (9/13). The concordance rate was relatively high (87.5%, 5/6) in tumors?<20?mm but lower (57.1%; 4/7) in tumors?≥20?mm. Regarding EUS findings, G2/G3 tumors were more likely to be large (>20?mm), heterogeneous, and have main pancreatic duct (MPD) obstruction than G1 tumors. Multivariate analysis showed large diameter and MPD obstruction were significantly associated with G2/G3 tumors. Conclusions: EUS and EUS-FNA are highly sensitive and accurate diagnostic methods for pNET. Characteristic EUS findings such as large tumor size and MPD obstruction are suggestive of G2/G3 tumors and would be helpful for grading pNETs.     

改进的比较基因组杂交方法

比较基因组杂交（ｃｏｍｐａｒａｔｉｖｅｇｅｎｏｍｉｃｈｙｂｒｉｄｉｚａｉｓｎ，ＣＧＨ）是直接检测全基因组中缺失和扩增的新方法，本工作对ＣＧＨ程序作了两处简化，这种改进的ＧＣＨ显示两个基本相同的基国组ＤＮＡ无差别，并能显示已知的染色体缺失和扩增。     

Usefulness of endoscopic ultrasound-guided fine-needle aspiration biopsy for the diagnosis of pancreatic cancer

Background Endoscopic ultrasonography-guided fine-needle aspiration biopsy (EUS-FNAB) has come into widespread use, mainly in Western countries, as an efficient and safe method for the cytologic or histologic diagnosis of pancreatic cancer. However, it still has received relatively little attention in Japan. To evaluate the clinical status of EUS-FNAB in Japan, we retrospectively analyzed the results with regard to the ability of EUS-FNAB to diagnose pancreatic cancer, as well as its safety. Methods A total of 52 patients (37 male, 15 female; mean age, 62.5 years; range, 33–85 years) with focal pancreatic lesions underwent EUS-FNAB at our group of hospitals in one region of Japan. Final diagnosis was confirmed by histologic examination of surgical specimens or clinical follow-up. Results The final diagnoses were malignant tumors in 32 patients and benign ones in 20. Insertion of the needle into the lesion was successful in 50 of the 52 patients (96.2%). Adequate specimens were obtained by EUS-FNAB from 47 of the 50 pancreatic lesions (94.0%). With five false-negative and no false-positive results, the accuracy, sensitivity, specificity, and positive and negative predictive values were 89.4%, 82.1%, 100%, 100%, and 79.2%, respectively. No complications occurred. Conclusions EUS-FNAB is an efficient and safe method for the histologic diagnosis of pancreatic cancer. It should be considered as one of the indispensable modalities for the histological diagnosis of pancreatic cancer in Japan, as it is in Western countries.     

内镜超声引导下细针穿刺抽吸术对胰腺癌的诊断价值

目的探讨内镜超声引导下细针穿刺抽吸术（EUS-FNA）对胰腺占位性病变特别是胰腺癌的诊断价值。方法对2005年后经B超、CT、MRI等影像学诊断和（或）临床疑诊胰腺癌的37例患者,在EUS引导下对病变作细针穿刺抽吸活检（FNA）,对于囊实性病变同时抽取囊液化验淀粉酶及肿瘤标志物等指标。结果EUS-FNA检出胰腺导管细胞癌16例,转移性肾细胞癌1例,可疑癌5例,异型细胞6例,正常胰腺组织6例,非胰腺成分3例。随访至2008年7月时,已证实胰腺癌25例,良性10例（慢性胰腺炎4例,囊腺瘤4例,假性囊肿2例）,尚有2例无法确诊。EUS-FNA诊断胰腺癌的敏感性为80．0％（95％CI：59．0-93．0）,特异性为100．0％（95％CI：60．0—100．0）,阳性预测值为100．0％（95％CI：80．0-100．0）,阴性预测值为55．6％（95％CI：27．0-79．0）。6例病变获取囊液进行淀粉酶、肿瘤标志物分析。本组EUS-FNA术后无严重并发症发生。结论EUS-FNA是一项安全有效的操作,对于胰腺占位性病变尤其是胰腺癌的诊断具有重要的意义。     

内镜超声引导下细针抽吸术获取胰腺癌组织构建体外三维类器官模型的前瞻性临床研究

目的 探讨通过内镜超声引导下细针抽吸术（EUS-FNA）获取胰腺癌组织构建体外三维类器官（organoid）模型的可行性。方法 自2017年6月至2018年1月前瞻性纳入发现胰腺占位并行EUS-FNA诊断的患者9例,术中使用COOK公司22 G穿刺针穿刺获取病灶组织构建体外类器官模型,并持续观察其体外生长状态。结果 9例患者EUS-FNA穿刺的胰腺病灶组织标本,其中5例体外类器官模型构建成功。这5例组织标本经组织病理学诊断均证实为胰腺癌。随着传代次数增加,类器官的生长速度相应加快,对类器官进行HE染色显示类器官与其来源的人胰腺病灶组织病理形态大致相似。结论 通过EUS-FNA穿刺获取人胰腺病灶组织,可以成功构建体外三维类器官模型。胰腺癌类器官模型的建立为临床上胰腺肿瘤患者精准治疗策略的制定提供了绝佳的模型。     

Age and cystic size are associated with clinical impact of endoscopic ultrasonography-guided fine-needle aspiration on the management of pancreatic cystic neoplasms

Objectives: The clinical impact of endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) in managing pancreatic cystic neoplasms (PCNs) remains controversial. The aim of this study was to identify which patients with PCNs would benefit from EUS-FNA.

Methods: A retrospective study was performed on patients with PCNs who underwent EUS-FNA between January 2009 and June 2018. A discordant or a consistent diagnosis after EUS-FNA was analyzed and was correlated with the clinical demographic data and cystic features. Predictors of the change in the diagnosis after EUS-FNA were analyzed.

Results: One hundred eighty-eight cases of PCNs were analyzed. EUS-FNA changed the diagnosis in 45.7% of all patients with PCNs and 54.5% patients with presumed branch ductal type intraductal papillary mucinous neoplasm (BD-IPMN) and impacted the recommendation in 35.6% of patients with PCNs and 50.5% patients with BD-IPMN. Patients with a discordant diagnosis after EUS-FNA were younger in age (54.8?±?12.6 vs. 61.2?±?14.2; p=.037) and had a cyst size larger than 3?cm than patients with a consistent diagnosis after EUS-FNA. The only worrisome feature (WF) that differed between patients with a discordant and a consistent diagnosis after EUS-FNA was the main pancreatic duct (MPD) between 5 and 9?mm (p=.013). In multivariate analysis, a cyst size >3?cm and age were independent predictors of diagnostic changes after EUS-FNA (OR: 5.33, 95% CI: 1.79–15.88, p?=?.003; OR: 0.96, 95% CI: 0.93–0.99, p = .031).

Conclusions: EUS-FNA made a significant change in the management of nearly half of the patients with PCNs, especially in younger patients and in patients with a cyst size larger than 3?cm.     

Comparative genomic hybridization detects genomic abnormalities in 80% of follicular lymphomas

Comparative genomic hybridization (CGH) was used to analyse 34 follicular lymphoma (FL) samples. 27 samples showed DNA sequence copy number changes of at least one genomic region (26 samples with at least one gain and nine with at least one loss). Some chromosomes or chromosomal regions were preferentially involved. The most frequently gained regions were chromosome 18q (29% of samples), chromosome X (21%), chromosome 7 (18%), chromosomes 2, 6p and 8q (12%). Two regions were preferentially lost: 6q (12%) and 17p (9%). All these gained and lost regions have been previously reported in cytogenetic studies, confirming the accuracy of CGH in detecting genetic abnormalities in FL. 21% of samples displayed normal profiles, probably reflecting the absence of unbalanced abnormality, which is also in agreement with the cytogenetic data. In conclusion, we showed that CGH is an accurate, reliable and rapid method and we propose the inclusion of CGH in the evaluation of FL at diagnosis.     

Ultrasound-guided vs endoscopic ultrasound-guided fine-needle aspiration for pancreatic cancer diagnosis

AIM: To clarify the effectiveness and safety of endo- scopic ultrasound-guided fine-needle aspiration (EUS-FNA) for the diagnosis of pancreatic cancer (PC). METHODS: Patients who were diagnosed with unresectable, locally advanced or metastatic PC between February 2006 and September 2011 were selected for this retrospective study. FNA biopsy for pancreatic tumors had been performed percutaneously under extracorporeal ultrasound guidance until October 2009; then, beginning in November 2009, EUS-FNA has been performed. We reviewed the complete medical records of all patients who met the selection criteria for the following data: sex, age, location and size of the targeted tumor, histological and/or cytological findings, details of puncture procedures, time from day of puncture until day of definitive diagnosis, and details of severe adverse events. RESULTS: Of the 121 patients who met the selection criteria, 46 had a percutaneous biopsy (Group A) and 75 had an EUS-FNA biopsy (Group B). Adequate cytological specimens were obtained in 42 Group A patients (91.3%) and all 75 Group B patients (P=0.0192), and histological specimens were obtained in 41 Group A patients (89.1%) and 65 Group B patients (86.7%). Diagnosis of malignancy by cytology was positive in 33 Group A patients (78.6%) and 72 Group B patients (94.6%) (P=0.0079). Malignancy by both cytology and pathology was found in 43 Group A (93.5%) and 73 Group B (97.3%) patients. The mean period from the puncture until the cytological diagnosis in Group B was 1.7 d, which was significantly shorter than that in Group A (4.1 d) (P < 0.0001). Severe adverse events were experienced in two Group A patients (4.3%) and in one Group B patient (1.3%). CONCLUSION: EUS-FNA, as well as percutaneous needle aspiration, is an effective modality to obtain cytopathological confirmation in patients with advanced PC.     

Diagnosis of solid pancreatic masses by endoscopic ultrasound-guided fine-needle aspiration

Background:  Endoscopic ultrasound (EUS) with fine-needle aspiration (FNA) is increasingly being used in the staging algorithm for pancreatic carcinoma. This allows for a tissue diagnosis, which was previously difficult to obtain. The aim of this study is to assess the utility of EUS–FNA in establishing the diagnosis of solid pancreatic mass lesions in an Australian population.
Methods:  A retrospective review of the EUS databases of St Vincent's Hospital Melbourne and Western Hospital, Melbourne from November 2002 to May 2006 was undertaken. The focus was on patients with a solid pancreatic mass who underwent EUS–FNA. Surgical pathology or long-term follow up was used to identify false-positive or false-negative results.
Results:  EUS was undertaken to investigate a solid pancreatic or distal common bile duct mass lesion in 155 patients. Seventy-two of these underwent EUS-guided FNA. Mean age was 68 years. A positive tissue diagnosis of malignancy could be made in 55 (76%). Nine (13%) had benign histology, with 8 (11%) having inadequate tissue obtained from FNA. A later tissue diagnosis of carcinoma was made in eight of those with either benign or inadequate histology, although in all cases there were EUS features diagnostic of malignancy, with FNA limited by technical difficulties. The overall utility of EUS–FNA showed a sensitivity of 87%, specificity 100%, positive predictive value 100%, negative predictive value 52% and overall accuracy 89%.
Conclusion:  EUS–FNA gives a high return for histological diagnosis of solid pancreatic mass lesions and should be part of the standard management algorithm for pancreatic carcinoma.     

Benefit of high negative pressure during endoscopic ultrasound-guided fine-needle aspiration with standard 22-gauge needles for pancreatic lesions: a retrospective comparative study

Objectives: Few studies are available on high negative pressure (HNP) during endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). This study compared the diagnostic yield between HNP and normal negative pressure (NNP) during EUS-FNA for solid pancreatic masses.

Methods: Consecutive patients with pancreatic masses who underwent EUS-FNA using a 22-G needle with either HNP or NNP for both the first and second passes were retrospectively examined for diagnostic yield. Rapid on-site evaluation (ROSE) was unavailable at our center. The main outcome measures were the number of passes, diagnostic accuracy and quantity of histological samples.

Results: Two hundred patients underwent EUS-FNA (n?=?97, HNP; n?=?103, NNP) over a 22-month period. A significantly lower median number of passes was required for HNP than for NNP (2 vs. 3; p?<?.001). There was no significant difference in diagnostic accuracy between the two groups. The rate of obtaining a histological sample larger than a 10× power field in length was significantly higher for HNP than for NNP (76.4% vs. 59.6%; p?=?.0019). In the multivariate analysis, a large tumor size (>20?mm) and HNP were identified as factors influencing the acquisition of a larger histological sample.

Conclusions: There was no significant difference in diagnostic accuracy between HNP and NNP. HNP required fewer passes without ROSE and was related to the acquisition of a larger histological sample. HNP may be useful when few samples are available for EUS-FNA with NNP or a larger histological sample is needed.     

Value of the p53 protein for diagnosing cancer in pancreatic cells obtained by endoscopic pancreatic duct brushing

OBJECTIVE: To investigate the value of the p53 protein for diagnosing cancer in pancreatic cells obtained by using endoscopic pancreatic duct brushing. METHODS: Immunohistochemical methods were used to assay the amount of p53 protein in cytological specimens. The results were compared with those obtained by hematoxylin and eosin (H&E) staining. RESULTS: Detection of the p53 protein by staining cytological specimens with H&E diagnosed pancreatic cancer with 53% sensitivity, 100% specificity and 70% accuracy. Using immunohistochemical methods, pancreatic cancer was diagnosed with 59% sensitivity, 100% specificity and 74% accuracy. The methods in combination produced a test with 71% sensitivity, 100% specificity and 81% accuracy. CONCLUSIONS: Hematoxylin and eosin staining combined with p53 protein detection in cells obtained by using endoscopic pancreatic duct brushing is a useful tool in the diagnosis of pancreatic cancer, and in the differentiation of benign and malignant pan­creatic disease.     

Diagnosis of pancreatic tumors by endoscopic ultrasound-guided fine-needle aspiration

AIM: To evaluate the diagnostic accuracy of endoscopic ultrasound-guided fi ne-needle aspiration (EUS-FNA) for pancreatic solid tumors larger or smaller than 3 cm, and cystic lesions. METHODS: From January/1997 to December/2006, 611 patients with pancreatic tumors were subjected to EUS-FNA. The fi nal diagnosis was obtained either by surgery (356 cases) or after a mean clinical follow-up of 11.8 mo in the remaining patients. RESULTS: There were 405 solid tumors, 189 cystic lesions and 17 mixed. Pancreatic specimens for cytological assessment were successfully obtained by EUS-FNA in 595 (97.4/) cases. There were 352 (57.6/) malignancies and 259 (42.4/) benign tumors. Among the malignancies, pancreatic adenocarcinomas accounted for 67/ of the lesions. Overall, the sensitivity, specifi city, positive and negative predictive values, and accuracy of EUS-FNA were, respectively, 78.4/, 99.2/, 99.3/, 77.2/ and 87.2/. Specif ically for solid tumors, the same parameters for neoplasms larger and smaller than 3 cm were, respectively, 78.8/ vs 82.4/, 100/ vs 98.4/, 100/ vs 99/, 54.8/ vs 74.1/ and 83.1/ vs 87.8/. For cystic lesions, the values were, respectively, 72.2/, 99.3/, 97.5/, 91/ and 92.2/. CONCLUSION: EUS-FNA can be used to sample pancreatic tumors in most patients. Even though the negative predictive value is inadequate for large solid tumors, the results are rather good for small solid tumors, especially concerning the sensitivity, negative predictive value and diagnostic accuracy. Among all pancreatic lesions, EUS-FNA for cystic lesions canreveal the best negative predictive value and diagnostic accuracy, both higher than 90/.     

Immunohistochemical analysis of IMP3 and p53 expression in endoscopic ultrasound-guided fine needle aspiration and resected specimens of pancreatic diseases

Background

Insulin-like growth factor II messenger ribonucleic acid-binding protein 3 (IMP3) is a valuable marker that distinguishes malignant from benign lesions and predicts prognosis.

Comparison of cytologic preparation methods in endoscopic ultrasound-guided fine needle aspiration for diagnosis of pancreatic adenocarcinoma

BackgroundThere are few studies about the diagnostic yield of cytologic preparation method of pancreatic samples obtained by Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). The aim of this study was to compare the accuracy of ThinPrep^® and smear method in diagnosis of pancreatic cancer.MethodsA total of 125 EUS-FNA procedures were performed between July 2010 and June 2015. Patients in group I (n = 36; July 2010 to June 2014) had cytology slides prepared by consecutive allocation of samples. Patients in group II (n = 12; July 2014 to June 2015) had cytology slides prepared by alternately allocation of samples.ResultsThere were 24 men and 24 women (median age: 67 years; range 39–84). The median size of lesions was 3.9 cm (range; 1.4–7.2 cm). The locations of the pancreatic cancer were 10 in head (20.8%), 21 in body (43.8%), and 17 in tail (35.4%). The ThinPrep^® method confirmed malignancy in 35 of 48 cases (72.9%). On the other hand, the smear method confirmed malignancy in 44 of 48 cases (91.7%). The diagnostic yield of smear method was statistically higher than liquid method (P = 0.012). Also, smear method is superior to liquid method in both consecutive and alternative allocation method. ThinPrep^® provided a correct diagnosis in one case where the smear method was incorrect.ConclusionsSmear method was a superior preparation method to liquid method in diagnosis of pancreatic cancer, even if splitting method was not used and variable allocation method was used.     

Value of repeat endoscopic ultrasound-guided fine needle aspiration for suspected pancreatic cancer

Background and Aims: Endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) is a safe and accurate technique for diagnosing pancreatic cancer. The value of repeat EUS‐FNA in patients with high clinical suspicion for pancreatic cancer after an inconclusive index study is unknown. Our aims were to determine the yield and success of repeat EUS‐FNA and the reasons for failure of initial EUS‐FNA. Methods: This was a retrospective analysis of prospectively collected data in a tertiary University based referral center for pancreatico‐biliary disorders. All patients who underwent more then one EUS‐FNA for evaluation of suspected pancreatic cancer over a five and a half year period were included in this analysis. Results: Of the 547 procedures performed on 517 patients, 24 (4.6%) patients underwent 51 repeat EUS‐FNA procedures. Initial EUS‐FNA was atypical/suspicious in 10 (41.6%), benign in 10 (41.6%), malignant in two (8.3%), and failed/indeterminate in two (8.3%) patients. Eight of 10 (80%) patients with atypical/suspicious findings at initial EUS‐FNA were diagnosed with malignancy on repeat EUS‐FNA. Of the 10 patients with benign findings at initial EUS‐FNA, repeat study diagnosed two (20%) with malignancy and the rest were confirmed benign on long‐term follow up (average 530 days, SD 369 days). Of the two patients with indeterminate findings at initial EUS‐FNA, repeat study diagnosed one patient with malignant disease and the other with benign disease that was confirmed by long‐term follow up. Of the two patients diagnosed with neoplastic disease at initial EUS‐FNA, repeat EUS‐FNA with immunostains downgraded both to chronic pancreatitis. Repeat EUS‐FNA facilitated determination of the true status of disease in 20 of 24 patients (accuracy 84%). Suspected reasons for failed initial EUS‐FNA were: coexisting pancreatitis (n = 10; 42%), technical difficulty due to scope positioning in uncinate lesion/sedation failure (n = 4; 16.7%), difficult cytology (partly cystic, extensive necrosis, well‐differentiated adenocarcinoma) (n = 4; 16.7%), presence of ascites or collaterals (n = 3; 12.5%), pathologist's interobserver variation (n = 2; 8.33%), and unknown reason in one patient. Conclusion: Repeat EUS‐FNA is warranted in patients with high clinical suspicion for pancreatic cancer despite indeterminate or negative findings at initial EUS‐FNA.     

超声内镜引导下细针穿刺活检对胰腺实性占位定性诊断价值的Meta分析

目的:系统评价超声内镜引导下细针穿刺活检(EUS-FNA)在胰腺实性占位定性诊断中的价值.方法:计算机检索MEDLINE、Cochrane Library、中国生物医学文献数据库、万方数据库、中国学术期刊全文等数据库,检索时间均为建库至2011-10.全面查找有关EUS-FNA诊断胰腺实性占位的文献,按照诊断试验的纳入标准筛选文献,提取纳入文献的特征信息(研究背景、设计信息和诊断参数信息),根据QUADAS质量评价标准纳入文献的质量.采用Meta-Disc1.4软件进行Meta分析,检验异质性,并根据异质性结果选择相应的效应模型.对纳入文献予以加权定量合并,计算汇总敏感度、特异度、阳性似然比、阴性似然比和诊断优势比及其95%CI,绘制汇总受试者工作特征(SROC)曲线,并计算曲线下面积(AUC).结果:共检索出相关文献280篇,按照文献纳入标准,最终纳入18篇文献(均为英文文献).EUS-FNA对胰腺实性占位定性诊断价值分别为:汇总敏感度为0.90[95%CI(0.89-0.92)],汇总特异度为0.95[95%CI(0.93-0.97)],汇总阳性似然比为13.56[95%CI(8.31-22.15)],汇总阴性似然比为0.12[95%CI(0.10-0.15)],汇总诊断优势比为143.62[95%CI(93.98-219.46)],SROC曲线下面积AUC为0.9711,Q*=0.9215.另外,本研究还对有无病理医生在场指导进行了亚组分析,发现有病理医生在场的AUC为0.9757,Q*=0.9295.且汇总诊断优势比173.37[95%CI(98.09-306.44)],明显较无病理医生在场的113.64[95%CI(60.22-214.46)]高.结论:经SROC曲线证实,EUS-FNA活检在胰腺实性占位定性诊断中具有较高的灵敏度和特异度,尤其是有病理医生在场指导的情况下,可作为临床上胰腺实性占位定性诊断的重要检查手段.