Role of endosonography in non-malignant pancreatic diseases

Endoscopic ultrasound (EUS) has emerged as a valuable tool in the evaluation of benign and malignant pancreatic diseases. The ability to obtain high quality images and perform fine-needle aspiration (FNA) has led EUS to become the diagnostic test of choice when evaluating the pancreas. This article will review the role of EUS in benign pancreatic diseases.     

仅表现为胰腺多发囊肿的Von Hippel-Lindau病一例并文献综述

患者男性．37岁。主诉“体重下降1个月”于2005年3月入院。患者1个月前无明显诱因出现体重下降，食欲及进食量较前无明显变化，无腹痛、腹淀，无多饮、多食、多尿，无低热、盗汗，病程中大小便正常，体重下降约5kg。既往2年前外院诊断“2型糖尿病”，平素规律服用达美康80mg bid，血糖空腹及餐后控制在正常范围。     

Pancreatic cystic manifestations in von Hippel-Lindau disease

Summary Conclusion In view of the frequent absence of symptoms related to pancreatic lesions, screening tests for VHL should always include assessment of the pancreas and, considering the frequency of polycystic manifestations, VHL should always be borne in mind in the differential diagnosis of multiple pancreatic cysts, especially when occurring in young patients and in the absence of a positive history of pancreatic disease. Background Von Hippel-Lindau disease (VHL) is a hereditary disease transmitted with an autosomal dominant character and characterized by hemangioblastomas of the central nervous system and retina, renal tumors and cysts, and pheochromocytoma. Pancreatic manifestations of VHL are reported in the literature with incidences ranging from 16 to 29% of cases and consist mainly in cystadenomas of the serous type and in multiple cystic lesions, often with complete replacement of the gland. Methods and Results We report five cases of VHL with a polycystic pancreas as the main or only manifestation, all devoid of symptoms related to involvement of the pancreas, who were referred to our Pancreatic Surgery center with diagnoses of multiple pancreatic pseudocysts of undefined origin.     

Carcino Embryonic Antigen and long-term follow-up of mucinous pancreatic cysts including intraductal papillary mucinous neoplasm

Background and aims

The utility of Carcino Embryonic Antigen (CEA) in differentiating malignant from benign pancreatic cysts is controversial. We sought to examine the role of CEA in differentiating benign from malignant cysts and its utility in progression of cyst size in follow-up.

Methods

Retrospective chart review of patients who underwent Endoscopic Ultrasound with Fine Needle Aspiration for mucinous cysts between 1998 and 2010. CEA was measured in benign and malignant mucinous cysts. Coefficient of determination (R²) was used to measure the association between change in cyst size and CEA. Mann–Whitney test was used to compare the median values of CEA.

Results

143 patients (38.4% males) were included (mean age 68.9 ± 0.8 years). 105 patients had intra-cystic CEA measured. 63 patients underwent surgery while 80 patients were in the follow-up group. In the surgical group, median CEA value for benign and malignant mucinous neoplasms was 796 and 438 ng/ml, respectively (p = 0.79). The median follow-up was 21 months. There was no correlation between CEA level and progression in cyst size in patients who had >6 months of follow-up, R² = 0.0002. Malignant transformation was observed in 5 (5.9%) patients.

Conclusion

CEA level was not predictive of malignant cyst nor cyst size progression over follow-up.     

Clinical approach to incidental pancreatic cysts

The approach to incidentally noted pancreatic cysts is constantly evolving. While surgical resection is indicated for malignant or higher risk cysts, correctly identifying these highest risk pancreatic cystic lesions remains difficult. Using parameters including cyst size, presence of solid components, and pancreatic duct involvement, the 2012 International Association of Pancreatology(IAP) and the 2015 American Gastroenterological Association(AGA) guidelines have sought to identify the higher risk patients who would benefit from further evaluation using endoscopic ultrasound(EUS). Not only can EUS help further assess the presence of solid component and nodules, but also fine needle aspiration of cyst fluid aids in diagnosis by obtaining cellular, molecular, and genetic data. The impact of new endoscopic innovations with novel methods of direct visualization including confocal endomicroscopy require further validation. This review also highlights the differences between the 2012 IAP and 2015 AGA guidelines, which include the thresholds for sending patients for EUS and surgery and methods, interval, and duration of surveillance for unresected cysts.     

Advanced diagnostics for pancreatic cysts: Confocal endomicroscopy and molecular analysis

Technological advances and the widespread use of medical imaging have led to an increase in the identification of pancreatic cysts in patients who undergo crosssectional imaging. Current methods for the diagnosis and risk-stratification of pancreatic cysts are suboptimal, resulting in both unnecessary surgical resection and overlooked cases of neoplasia. Accurate diagnosis is crucial for guiding how a pancreatic cyst is managed, whether with surveillance for low-risk lesions or surgical resection for high-risk lesions. This review aims to summarize the current literature on confocal endomicroscopy and cyst fluid molecular analysis for the evaluation of pancreatic cysts. These recent technologies are promising adjuncts to existing approaches with the potential to improve diagnostic accuracy and ultimately patient outcomes.     

Diagnosis and management of pancreatic neuroendocrine tumor in von Hippel-Lindau disease

The pancreatic manifestations seen in patients with von Hippel-Lindau(VHL) disease are subdivided into 2 categories:pancreatic neuroendocrine tumors(NET),and cystic lesions,including simple cyst and serous cystadenoma.The VHL-associated cystic lesions are generally asymptomatic and do not require any treatment,unless they are indistinguishable from other cystic tumor types with malignant potential.Because pancreatic NET in VHL disease are non-functioning and have malignant potential,it is of clinical importance to find and diagnose these as early as possible.It will be recommended that comprehensive surveillance using dynamic computed tomography for abdominal manifestations,including pancreatic NET,should start from the age of 15 years in VHL patients.Unlike sporadic non-functioning NET without VHL disease,in which surgical resection is generally recommended,VHL patients at lower metastatic risk of pancreatic NET should be spared the risks of operative resection.     

The utility of intracystic glucose levels in differentiating mucinous from non-mucinous pancreatic cysts

BackgroundDifferentiating benign non-mucinous from potentially malignant mucinous pancreatic cysts is still a challenge. This study aims to improve this distinction with cyst fluid analysis.MethodsA cohort study of pancreatic cyst undergoing EUS/FNA was performed from a prospectively maintained database between 2014 and 2018 was performed.Results113 patients were analyzed (40 non-mucinous and 73 mucinous). For differentiating mucinous from non-mucinous cyst: intracyst glucose ≤41 mg/dl had a sensitivity of 92% and a specificity of 92%; positive predictive value (PPV) of 96 and negative predictive value (NPV) of 86. Glucose ≤21 mg/dl had a sensitivity of 88%, specificity of 97%, PPV of 98 and NPV of 81. CEA ≥192 ng/mL had a sensitivity of 50% and a specificity of 92%; PPV of 92 and NPV of 50. Glucose ≤21 mg/dl or CEA ≥192 ng/mL combined had a sensitivity of 93%, specificity of 92%, PPV of 96 and NPV of 87 (Fig. 1, Table 1).ConclusionIntra-cyst glucose levels (≤41 mg/dl) outperforms classic CEA testing for differentiation of mucinous from non-mucinous pancreatic cysts. It was found to be an excellent diagnostic test with an AUC of 0.95 (95% CI: 0.81, 0.97).     

Massive postoperative ascites following pancreatic cysts fenestration in a patient with von Hippel-Lindau disease

Pancreatic lesions in von Hippel Lindau disease (VHLD) are frequent and mainly consist of cystic lesions, which should not be resected because of their benign evolution. Solid lesions, mostly pancreatic endocrine tumors (PET), are rare and usually occur in combination with cystic lesions. We report a case of a patient with VHLD who underwent PET enucleation in a polycystic pancreas requiring fenestration of multiple adjacent cysts, to ensure complete resection with free resection margins. The postoperative course was complicated by massive ascitic fluid effusion, probably related to pancreatic-cyst fenestration. Although this complication is well-known after liver-cyst fenestration, it has not been reported after pancreatic-cyst fenestration. This observation emphasizes that morbidity from surrounding pancreatic polycystic disease should not be underestimated in pancreatic surgery for VHLD.     

超声内镜与B超诊断胰腺疾病的对比分析

目的 探讨超声内镜(EUS)和B超对胰腺疾病的诊断价值。方法 对1999年6月至2001年6月期间123例胰腺疾病患行EUS检查并与体表B超检查结果进行比较。结果 63例胰腺癌、45例胰腺炎和11例其它胰腺疾病患经EUS确诊。38例胰腺癌，28例胰腺炎和5例其它胰腺疾病经US确诊。EUS诊断胰腺疾病的敏感性与准确性均明显高于B超，EUS与B超诊断符合率分别为96．7％(119／123)与56．9％(70／123)(P＜0．01)。结论 EUS在胰腺疾病诊断中有较高的特异性和准确性，与B超联合应用有助于胰腺疾病的诊断。     

超声内镜引导125I粒子组织间植入治疗晚期胰腺癌的疗效及粒子移位分析

目的分析胰腺癌超声内镜（EUS）引导下^125I粒子种植术治疗晚期胰腺癌的肿瘤变化及粒子移位，并评价其治疗效果。方法对17例不能手术切除的中晚期胰腺癌患者行EUS引导下放射性^125I粒子内照射治疗。所有患者治疗前均参照治疗设计系统估算期望植入粒子数量。治疗后每月复查，观察治疗前、后肿瘤变化及粒子移位、脱落等情况。结果17例患者均经EUS植入^125I粒子成功。治疗前肿瘤最大长径平均值为5．4cm（3．7～9．0cm），平均植入粒子数量为27颗，平均每次植入粒子中位数为14（7～24）颗，平均植入2次。平均单颗粒子的放射性活度为（0.689±0．016）mCi。治疗后平均随访4．8个月（2～14个月）。治疗后3个月评估疗效，部分缓解5例（29．4％），疾病稳定7例（41．2％），进展恶化5例（29．4％）。治疗后腹部平片示5例（29．4％）出现粒子丢失移位。1例脾区移位，1例肝脏移位，3例肠腔移位。治疗后粒子丢失4例。1例出现脾脏及左膈下囊肿。结论EUS引导下^125I粒子内照射治疗晚期胰腺癌，可使粒子照射区域内病灶明显萎缩。但需注意放射性粒子对周围脏器的损害及粒子脱落移位等并发症的发生。     

贵州省一家族性VonHippel-Lindau病的临床诊治和随访

目的分析贵州省一家族性VonHippel—Lindau病的临床特点、影像学表现、诊断治疗方法和预后。方法回顾性分析贵阳医学院附属医院1997年3月至2011年11月收治的1个家族性血管母细胞瘤家系（38人）7例患者的病史、临床表现、影像学相关资料。结果7例患者均未合并其他部位病变,MRI显示6例为实质性肿瘤,1例囊性肿瘤;4例患者共进行7次显微手术,切除血管母细胞瘤10枚,术后随访1例血管母细胞瘤在不同部位反复复发又经2次开颅手术、2次伽玛刀放射治疗;先证者在术后6年异位复发,复发病灶约为1mm,未予处理,继续随访;1例进行激光治疗视网膜血管瘤;2例症状不明显进行随访,在随访中未见新发病灶,原病灶也未增大。结论对于家族性血管母细胞瘤,头颅MRI检查是主要的诊断及随访方法,显微手术切除是主要治疗手段,立体定向放射治疗可作为补充治疗方法。由于家族性血管母细胞瘤易合并其他部位病变、复发率高、常为多发病灶,应加强对整个家族成员追踪随访和基因检测。     

超声内镜细针穿刺研究胰腺组织中微小核糖核酸的表达及临床意义

目的 研究超声内镜(EUS)-细针穿刺(FNA)胰腺组织中微小核糖核酸(miRNA)的表达及临床意义.方法 用实时定量逆转录-聚合酶链反应方法 检测23例胰腺癌和13例胰腺良性占位病变的EUS-FNA组织标本中miRNA-210、miRNA-21、miRNA-196a、miRNA-181a、miRNA-181b、miRNA-155和miRNA-16的表达并分析其临床意义.结果 胰腺癌中miRNA-210、miRNA-21、miRNA-196a、miRNA-181a、miRNA-181b的相对表达量分别为0.86±1.10、0.69±0.64、0.32±2.50、0.16±0.83、0.56±0.88,均较胰腺良性占位病变中(分别为-0.11±0.98、-0.03±0.97、-1.50±1.40、-0.53±1.10、-0.28±1.10)显著升高,P值分别=0.012、0.011、0.024、0.036、0.015.miRNA-16、miRNA-155在胰腺癌组织和胰腺良性占位病变中的相对表达量分别为-0.11±0.69、0.08±1.04和-0.73±1.26、-0.19±1.19,差异均无统计学意义(P值分别=0.067和0.467).miRNA-196a高表达与胰腺癌淋巴结转移和TNM分期正相关.结论 胰腺癌发生中存在多条miRNA异常高表达,其中miRNA-196a与胰腺癌临床恶性特征相关.     

Advances in the endoscopic management of pancreatic collections

Treatment of pancreatic collections has experienced great progress in recent years with the emergence of alternative minimally invasive techniques comparing to the classic surgical treatment. Such techniques have been shown to improve outcomes of morbidity vs surgical treatment. The recent emergence of endoscopic drainage is noteworthy. The advent of endoscopic ultrasonography has been crucial for treatment of these specific lesions. They can be characterized, their relationships with neighboring structures can be evaluated and the drainage guided by this technique has been clearly improved compared with the conventional endoscopic drainage. Computed tomography is the technique of choice to characterize the recently published new classification of pancreatic collections. For this reason, the radiologist’s role establishing and classifying in a rigorously manner the collections according to the new nomenclature is essential to making therapeutic decisions. Ideal scenario for comprehensive treatment of these collections would be those centers with endoscopic ultrasound and interventional radiology expertise together with hepatobiliopancreatic surgery. This review describes the different types of pancreatic collections: acute peripancreatic fluid collection, pancreatic pseudocysts, acute necrotic collection and walled-off necrosis; the indications and the contraindications for endoscopic drainage, the drainage technique and their outcomes. The integrated management of pancreatic collections according to their type and evolution time is discussed.     

超声内镜对胰腺癌诊断及评估价值

目的：探讨EUS诊断胰腺癌的敏感性，准确性及其评估肿瘤特征的价值。方法：以126例经病理确诊并在确诊前半月内先后接受EUS、US、CT检查的胰腺癌患者为研究对象，回顾性分析三种成像方法及EUS对于不同类型胰腺癌的检查结果，应用t检验或u检验评估这些检查结果的差异有无显著性，结果：EUS诊断胰腺癌准确性较US高，尤其对于小胰腺癌准确性更高，二者差异有显著性（P＜0．05）；EUS诊断敏感性，准确性与CT比较差异无显著性，联合应用EUS及CT检查，则诊断敏感性及准确性大为提高，与单独应用US、EUS或CT相比，差异均有显著性（P＜0．05）；EUS与CT显示肿瘤间接征象的准确性无显著性差异，结论：EUS对于胰腺癌是一种较好的检查方法，尤其对于怀疑为小胰腺癌者应作为常规检查，联合应用EUS和CT检查胰腺癌值得推广。     

内镜超声引导下细针穿刺活检对胰腺占位性病变的诊断价值

目的探讨内镜超声引导下细针穿刺活检（EUS—FNA）对胰腺占位性病变的诊断价值。方法从1998年10月至2006年9月，对190例胰腺占位病灶进行了超声内镜引导下穿刺活检，进行细胞学或病理学诊断。结果（1）2006年1月以前未采用床旁染色观察时，EUS—FNA诊断胰腺癌的敏感性为67．6％。2006年1月以后采用病理医师床旁瑞氏-姬姆萨快速染色观察法，EUS—FNA诊断胰腺癌的敏感性提高到93.1％。（2）18例胰腺小占位病灶行EUS—FNA，其诊断准确率是66．7％。（3）胰腺癌患者组中EUS—FAN活检物中的CEA、CA19-9浓度明显高于血清中的浓度。（4）EUS—FNA对假肿瘤性胰腺炎诊断的准确率为76．5％。结论EUS—FNA对胰腺占位性病灶的诊断是安全有效的，具有重要价值。     

Endoscopic ultrasound guided fine-needle aspiration and biopsy of pancreatic cysts

Pancreatic cystic lesions (PCLs) are often incidentally found on cross-sectional imaging. Long strides have been made in the past decade with improved quality and optics of cross-sectional imaging and endoscopic ultrasound (EUS), but a singular reliable test to appropriately characterize and risk-stratify PCLs has still eluded us. EUS allows high-resolution imaging of the pancreatic parenchyma and the ductal system, for assessment of PCL characteristics, with features concerning for malignancy and additionally provides an opportunity to sample the cyst to obtain fluid or cells for further diagnostic testing. This presents new sets of challenges, which include devising suitable equipment or needles and techniques for reliable and safe tissue acquisition, as well as provision of an adequate cytology or tissue sample to the pathologist, in order to arrive at an accurate diagnosis. This article will review the current role of EUS in the diagnosis and characterization of PCLs, with a focus on available strategies and pitfalls of cytology, cyst-fluid biomarkers, and biopsy acquisition techniques; and future directions to increase the yield and accuracy.     

胰腺超声内镜细针穿刺活检组织中粘蛋白表达检测辅助诊断胰腺癌的价值评价

目的 检测粘蛋白（MUCl、MUC2、MUC5AC）在胰腺超声内镜细针穿刺（EUS-FNA）组织标本中的表达，评价其对胰腺癌辅助诊断的价值。方法 收集54例胰腺占位病变的EUS-FNA组织标本，采用S-P免疫组化法检测粘蛋白（MUCl、MUC2、MUC5AC）的表达，根据临床综合判断的诊断，与细胞学检查结果比较，评价其诊断价值。结果 54例患者最后确诊为胰腺癌38例，胰腺良性肿瘤6例，慢性胰腺炎10例。细胞学和组织学的诊断敏感性分别为31．6％和47．4％。MUC1、MUC2、MUC5AC在胰腺癌EUS-FNA标本组织中的阳性表达率为81．6％（31／38）、10．5％（4／38）、84．2％（32／38），在胰腺良性疾病组织标本中分别25％（4／16）、31．3％（5／16）、43．8％（7／16），其中MUCl和MUC5AC两组间差异有统计学意义（P〈0．01）。MUCl的表达与胰腺癌的临床分期、淋巴结转移呈正相关。将细胞组织学检查结合MUCl和MUC5AC表达检测诊断胰腺癌的敏感性可提高至89．5％。结论胰腺EU$-FNA组织标本中MUCl、MUC5AC的检测对胰腺癌有临床辅助诊断价值，且MUCl还能预测胰腺癌的临床分期及淋巴结转移。     

Pancreatic involvement in Korean patients with von Hippel-Lindau disease

Purpose  The aim of this study was to describe pancreatic involvement in von Hippel-Lindau (VHL) disease and to document the changes that occur in pancreatic lesions. Methods  We retrospectively analyzed the medical records and CT scans of 18 VHL patients who were diagnosed between 1994 and 2007 at the Samsung Medical Center. The clinical history with a detailed family history, biochemical test results, and imaging studies of the pancreas, adrenal glands, and kidneys were reviewed. Genetic analysis was performed in 12 patients. The changes in pancreatic lesions, such as an increase in cystic lesions, calcifications, and dilatation of the pancreatic duct, were analyzed in patients who had CT scans at least 1 year apart. Results  Pancreatic lesions existed in 89% (16/18) of the patients. All 16 patients had multiple cystic lesions. Two patients had co-existing neuroendocrine tumors (NET), and two patients had co-existing serous cystadenomas (SCA). At least one of three features of pancreatic lesions (cystic lesions, calcifications, and dilatation of the pancreatic duct) progressed in all nine patients who had CT scans 1 year apart. Conclusion  Pancreatic involvement in VHL disease was relatively common in Korean patients. The most common type of pancreatic involvement was a multiple cystic lesion. NET and SCA existed in approximately 10% of VHL patients with pancreatic involvement. Pancreatic lesions in VHL disease progressed, at least according to radiological images.     

Similarities and differences in guidelines for the management of pancreatic cysts

Accurate diagnosis of Pancreatic cysts(PC) is key in the management. The knowledge of indications for surgery, the role of endoscopic ultrasound-guided fine needle aspiration, cyst fluid analysis, imaging, and surveillance of PC are all important in the diagnosis and management of PC. Currently, there are many guidelines for the management of PC. The optimal use of these guidelines with a patient-centered approach helps diagnose early cancer and prevent the spread of cancer.