胰腺内分泌肿瘤细胞成分的免疫细胞化学观察及其对肿瘤起源的探讨

目的 探讨胰腺内分泌肿瘤的生物学起源。方法 应用链菌素亲生物素－过氧化物酶标免疫组织化学学技术（Ｓ－Ｐ法）对５２例胰腺内分泌肿瘤（胰岛素瘤３２例，非功能性胰腺内分泌肿瘤２０例）瘤细胞内胰岛素、胰高血糖素、舒血管肠太、生长抑素、胃泌素、Ｐ－物质、促肾上腺皮质激素、绒毛膜促性腺激素及５－羟色胺等９种激素或激素类物质的分布进行了观察。结果 ６５．５％（１３／２０）的非功能性胰腺内分泌肿瘤的细胞具有合成与     

胰腺胰岛肿的免疫组织化学研究

本研究对最常见的胰岛素瘤和非功能性内分泌肿瘤进行正分泌激素 ,异位激素等的免疫组织化学研究 ,以探讨其免疫组化特征及其意义和免疫组化在诊断胰腺内分泌肿瘤(ｐａｎｃｒｅａｔｉｃｅｎｄｏｃｒｉｎｅｔｕｍｏｒ,ＰＥＴ)中的作用。　　一、对象和方法1.对象 :17例胰腺肿瘤均为上海市第六人民医院 1976年 1月至 1997年 12月收治的手术病例。男 8,女 9,2 4～ 70岁 ,平均 46 .2岁 ,病程 1个月～ 10年。临床表现为 9例反复发作的低血糖性昏迷 ,血糖 0 .5～ 2 .2ｍｍｏｌ/Ｌ ,4例血清胰岛素 2 5～ 36ｍＵ/Ｌ ,临床诊断胰岛细胞瘤。 8例非内分…     

胰腺内分泌肿瘤的诊断及手术治疗

目的探讨胰腺内分泌肿瘤(PET)的诊断及手术治疗方法。方法对27例PET患者的临床资料作回顾性分析。结果胰岛素瘤17例[均有明显的Whipple三联征,术前随机最低血糖(1.72±0.66)mmol/L,胰岛素释放试验空腹胰岛素水平(68.3±44.53)mIU/L]、胃泌素瘤1例(表现为周期性、规律性上腹痛,血清胃泌素220pg/ml)、胰高血糖素瘤2例(1例表现为典型的迁移性坏死性皮炎,1例首先表现为急性腹痛)、无功能性胰岛细胞瘤7例(均以腹部包块就诊)。B超、CT、DSA、术中B超检查发现病灶者分别为15、19、8、17例。行病灶切除17例、胰体尾切除7例、活检3例。结论 PET以胰岛素瘤及无功能性胰岛细胞瘤最常见;胰岛素瘤临床有典型表现,其他肿瘤表现不典型。术中B超检查有助于本病的定位诊断。手术治疗方式多根据肿瘤大小及性质决定。     

胰腺神经内分泌肿瘤

胰腺神经内分泌肿瘤（PNET）临床少见,表现为功能性和无功能性,来源于胰岛细胞,又称为胰岛细胞瘤（ICTs）。PNET是胰腺肿瘤很重要的一种类型,约占临床诊断胰腺肿瘤的2％-4％,包括单发、多发,良性、恶性等多种类型,其中10％～20％伴有多发内分泌肿瘤（MEN）。     

胰腺内分泌肿瘤的诊断及手术治疗

对28例经手术治疗、病理检查证实的胰腺内分泌肿瘤（PETs）患者的临床资料作回顾性分析。发现PETs以胰岛素瘤、胰多肽瘤最常见,肿瘤大小与症状轻重无关;胰岛素瘤体积较小,术前定位诊断较难;胰多肽瘤无特定性症状,术前定性诊断较难。本组胰岛素瘤18例,均为良性,其中15例行单纯肿瘤切除术;胃泌素瘤1例为恶性,行胰尾联合全胃切除术;胰高血糖素瘤2例均为恶性,术中发现肝转移,1例行胰体尾联合肝转移灶切除术,1例行姑息性切除;胰多肽瘤7例,4例行肿瘤切除术,3例伴肝转移者中,1例行胰体尾姑息性切除术,2例无法切除。认为PETs术前诊断比较困难;手术切除是PETs最理想的治疗方法,手术方式根据肿瘤生长部位和性质而定。     

胃肠神经内分泌肿瘤和胰腺神经内分泌肿瘤的区别

胃肠胰神经内分泌肿瘤（GEP-NETs）主要来源于胃肠胰系统的神经内分泌细胞,这一细胞系统和肿瘤是以表达细胞类型特异的肽激素和普通标记物（突触囊泡蛋白、铬粒素A）为特征。其特点为：临床上少见;肿瘤通常较小（〈1 cm）;生长速度较慢（数月或数年）,呈阶段性表达,可能数年无症状;通常在出现症状前即有转移,转移部位多为肝脏和骨,而此时肿瘤的体积通常〉2cm。因此这类肿瘤经常被误诊,诊断过程较复杂,不单单依靠临床,往往需要高端的实验室和扫描手段支持。而GEP-NETs中胃肠神经内分泌肿瘤（NET）和胰腺NET,两者在临床表现、诊断和治疗方面也有不同,需要临床医生重视和加以区分。     

胰腺内分泌肿瘤的诊断

胰腺内分泌肿瘤(PET)是一类少见的、发展缓慢的、最终为恶性的肿瘤,其临床表现因分泌激素的多样性而呈多种类型。生长抑素受体闪烁成像有助于鉴别CT所发现的胰腺肿瘤是否为PET。血以及肿瘤组织铬粒素A是PET最有价值的共同标记物。检测血和组织相应的胃肠激素水平,可确定PET的具体种类。临床诊断PET时,应注意排除多发性内分泌瘤(MEN-Ⅰ)。     

胰腺神经内分泌肿瘤诊治进展

胰腺神经内分泌肿瘤(pNEN)是一种较为罕见的胰腺肿瘤,多为散发病例,约10%具有遗传倾向。据其是否分泌功能性激素,可分为功能性和非功能性。pNEN药物治疗可分为控制激素相关临床症状和控制肿瘤生长两类。手术是重要治疗手段之一,此外还可考虑射频消融、放射性核素治疗等方法。因pNEN诊治过程涉及多个科室,推荐多学科诊疗综合评估制定诊治方案。     

胰腺神经内分泌肿瘤的诊治进展

胰腺神经内分泌肿瘤(pancreatic neuroendocrine tumors,PNETs)是源于胰腺多能神经内分泌干细胞的一类肿瘤,故又称胰岛细胞瘤,临床少见或罕见,其发病率约为4~5/100万。该病经积极手术治疗后效果较好,但是由于PNETs自身类型多样,症状复杂多变,临床表现各异,在临床诊疗中极易造成误诊和漏诊。因此,早期正确的诊断是有效治疗PNETs的重要前提。该文针对目前胰腺神经内分泌肿瘤的诊治进展作一系统综述。     

分泌VIP和CCK的胰腺内分泌肿瘤一例

本文首次报道一例同时分泌ＶＩＰ和ＣＣＫ的胰腺内分泌肿瘤，表现为水样泻、低钾血症、高胃酸分泌并导致顽固性十二指肠溃疡伴出血。报道如下。患者男，５８岁，因间断上腹疼、黑便４年，发现肝内囊性占位性变３年，水样泻９个月，于１９９６年８月１４日入院。患者４年来...     

Immunohistochemical analysis of cyclooxygenase-2 expression in pancreatic tumors

Summary Background A considerable amount of evidence collected from several experimental systems and clinical studies with nonsteroidal Anti-inflammatory drugs (NSAIDs) indicates that Cox-2 may play a major role in colorectal tumorigenesis, but little information about Cox-2 expression in pancreatic tumors is available. In this study, we investigated Cox-2 expression by means of both immunohistochemical analysis and immunoblot analysis in pancreatic tumors. Methods Fifty invasive ductal adenocarcinomas and 26 intraductal papillary-mucinous tumors (IPMTs) were used for immunohistochemical analysis, and five pancreatic cancer tissues and five pancreatic cancer cell lines for immunoblot analysis. Results Cox-2 was expressed in 72% of the invasive ductal adenocarcinomas, 31% of intraductal papillary-mucinous adenocarcinomas, and none of intraductal papillary-mucinous adenomas. The expression rate of Cox-2 in intraductal papillary-mucinous adenocarcinomas was significantly higher than that in intraductal papillary-mucinous adenomas, and that in invasive ductal adenocarcinomas was significantly higher than that in intraductal papillary-mucinous carcinomas. However, there was no significant correlation between Cox-2 expression and the prognosis and clinicopathological factors. Immunoblot analysis identified Cox-2 in all of pancreatic cancer tissues and 60% of cell lines. Conclusion The biological role of cyclooxygenase-2 (Cox-2) in carcinoma cells should be investigated with reference to the cancer progression of the pancreas.     

Ductal and acinar differentiation in pancreatic endocrine tumors

Rare pancreatic endocrine tumors consisting of both exocrine and endocrine components have been reported sporadically. We investigated the ductal and acinar differentiation in pancreatic endocrine tumors. In immunohistochemical studies of 28 pancreatic endocrine tumors, staining with anti-carcinoembryonic antigen (CEA) or CA19-9 antibody indicated ductal differentiation, while staining with anti-amylase or anti-trypsin antibody indicated acinar differentiation. K-ras gene mutations and p53 gene alterations also were studied. Ten tumors were immunoreactive for CEA or CA19-9. Five tumors diffusely immunoreactive for CEA or CA19-9, in addition to endocrine markers, were diagnosed as duct–endocrine cell tumors of the pancreas. Two tumors diffusely immunoreactive for CEA or CA19-9 and also for pancreaticogut hormones as well as endocrine markers were diagnosed as duct–acinar–endocrine cell tumors. These tumors showed uniform histologic features and synchronous ductal, acinar, and endocrine differentiation, distinct from the coexisting different cellular populations seen in collision tumors. All tumors were malignant. These duct–endocrine cell tumors or duct–acinar–endocrine cell tumors of the pancreas may be derived from a stem cell that retains the capability of expressing either an exocrine or endocrine phenotype. Only one K-ras gene mutation and no p53 gene alterations were detected in these tumors, which suggests that they constitute an entity with a different origin than ductal carcinomas.     

Small serotonin-positive pancreatic endocrine tumors caused obstruction of the main pancreatic duct

We report 2 cases of pancreatic endocrine tumors that caused obstruction of the main pancreatic duct (MPD). A 49-year-old asymptomatic man was referred to our institution because dilation of the MPD was revealed by abdominal ultrasonography (US). No tumor was detected by endoscopic ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI). The diameter of the MPD was > 20 mm at the body, and no dilation was noted at the head. Although malignancy was not confirmed through cytology or imaging, pancreatic cancer was strongly suspected. Pancreaticoduo- denectomy was performed. Pathological and immunohistochemical examination revealed a 5 mm × 3 mm serotonin-positive endocrine tumor. Fibrosis was present around the MPD and seemed to cause stricture. A 32-year-old asymptomatic man had elevated serum amylase, and US demonstrated dilation of the MPD. No tumor was detected by CT and MRI. Pancreatic cancer was suspected due to stricture and dilation of the MPD. Pancreatectomy of middle part of pancreas was performed. Pathological and immunohistochemical examination revealed a serotonin-positive endocrine tumor sized 5 mm × 4 mm. We report 2 cases of serotonin-positive pancreatic endocrine tumors that caused stricture of the MPD in spite of the small size of the tumor.     

Advancements in pancreatic neuroendocrine tumors

Pancreatic neuroendocrine tumors (PanNETs) have increased in incidence in the USA over the last 20 years. Although PanNETs are often misconceived as being indolent tumors as they have a far more favorable prognosis over pancreatic adenocarcinoma, roughly 60–70% of patients have metastatic disease at the time of diagnosis due to presentation late in the disease process. While improvements in imaging modalities allow for early detection and better tumor localization, recent advancements in basic science, as well as surgical and medical management of PanNETs have further improved the prognosis. The mainstay of therapy for localized PanNETs is surgical intervention, which has become safer and is slowly shifting towards a more minimally invasive approach. However, the prognosis still remains relatively bleak for patients with unresectable disease. Fortunately, novel molecular targeted therapies, such as everolimus and sunitinib, have recently come into the limelight and have shown significant promise for the treatment of locally advanced and metastatic disease.     

EUS-guided FNA diagnosis of pancreatic endocrine tumors: new trends identified

BACKGROUND: Pancreatic endocrine tumors (PETs) are rare (1 per 100,000 population) and are thought to be functioning in up to 85% of cases and are generally less than 2 cm in size. By previous reports, 15% to 50% of PETs are nonfunctioning and are discovered either incidentally or by symptom evaluation from a mass effect. EUS-guided FNA (EUS-FNA) has been shown to accurately diagnose PETs and to localize tumors for surgical resection. OBJECTIVE: To describe a single-center experience of EUS-FNA diagnosis of PETs and its impact on surgical management. DESIGN: Retrospective cohort study. SETTING: University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. PATIENTS: Patients with PETs diagnosed via EUS-FNA over a 4-year period were identified through the authors' EUS database. Clinical history, laboratory values, diagnostic studies, EUS findings, cytology, pathology, operative records, and surgical pathology records were reviewed. MAIN OUTCOME MEASUREMENT: Impact of definitive preoperative diagnosis of PET on surgical management. RESULTS: Forty-one patients were diagnosed by EUS-FNA with PET. Thirty-five PETs were nonfunctioning PET; 6 were functioning PET. The mean tumor sizes of functioning and nonfunctioning PETs were 19 mm and 28 mm, respectively. The majority of tumors were located in the pancreatic head. Surgery was performed in 78% of patients; of these, 34% were resected laparoscopipcally. LIMITATIONS: Retrospective design and selection bias. CONCLUSIONS: In this study, nonfunctioning PETs were more commonly diagnosed compared with functioning PETs. In addition, the PETs were smaller than previously reported, likely because of increasing detection of incidental lesions through widespread use of abdominal imaging.     

Immunocytochemical staining for islet amyloid polypeptide in pancreatic endocrine tumors

Aims/hypothesis: Islet amyloid polypeptide is originally identified as the chief constituent of amyloid in insulinomas and type 2 diabetic islets. This study aimed to identify islet amyloid polypeptide by immunocytochemical staining in pancreatic endocrine tumors including 30 cases of insulinomas and non-β-cell pancreatic endocrine tumors. Results: In normal islets, 62% of islet cells and 52% of insulin cells were granularly positive for insulin and IAPP, respectively, with more insulin positive cells than IAPP positive cells and some densely positive staining for insulin and IAPP in irregularly shaped a nuclear, degenerating islet β-cells. In pancreatic endocrine tumors, all 10 insulinomas were positive for islet amyloid polypeptide but 2 glucogonomas, 1 somatostatinoma, 6 of 7 pancreatic polypeptidomas, all 7 gastrinomas and all 3 non-functioning pancreatic endocrine tumors were negative for islet amyloid polypeptide whereas one pancreatic polypeptidoma was positive for islet amyloid polypeptide. Methods: Using commercially available rabbit anti-islet amyloid polypeptide antibody, immunocytochemical staining was performed on 30 cases of pancreatic endocrine tumors, consisting of 10 insulinomas, 2 glucagonomas, 1 somatostatinoma, 7 pancreatic polypeptidomas, 7 gastrinomas and 3 non-functioning pancreatic endocrine tumors. Pancreatic tissues containing pancreatic endocrine tumors were systematically immunostained for insulin, glucagon, somatostatin, pancreatic polypeptide, gastrin and chromogranin A, in addition to islet amyloid polypeptide. When normal pancreatic tissues adjacent to pancreatic endocrine tumors were present, insulin, glucagon, somatostatin and islet amyloid polypeptide positive cells were counted for a total of 20 islets, which were divided into large islets and medium islets for each case. Conclusions/Interpretations: All 10 insulinomas and 1 pancreatic polypeptidoma were granularly positive for islet amyloid polypeptide, suggesting all 10 insulinomas contained enough insulin granules for IAPP whereas only one non-β-cell pancreatic endocrine tumor was co-localized with islet amyloid polypeptide in their secretary granules.     

Expression of the coiled coil domain containing protein 116 in the pancreatic islets and endocrine pancreatic tumors

Aims: Coiled coil domain containing protein 116 (CCDC116) is a product of the gene coiled coil domain containing 116 located on human chromosome 22. Its function has not yet been established. The present study focuses on the expression of this protein in human pancreatic islets and in the endocrine pancreatic tumors (EPTs). Methods and Results: Expression of the protein was evaluated by immunohistochemistry in endocrine pancreas from six patients and in various EPTs from 51 patients. In pancreatic islets, virtually all insulin, approx. 75% of the somatostatin, and approx. 60% of the pancreatic polypeptide (PP) cells were immunoreactive for the CCDC116 protein whereas glucagon, ghrelin and the exocrine cells were not. All insulinomas, gastrinomas, non-functioning sporadic tumors and the hereditary multihormonal EPTs were immunoreactive with variable relative incidence. Two of the three somatostatinomas, and one of the three ACTH-secreting tumors also expressed CCDC116. Conclusions: The CCDC116 protein is expressed in all islet cell types except the glucagon and ghrelin cells. Most of the EPTs also contained CCDC116 protein. These findings suggest that this protein may play some role for the above mentioned endocrine cells and tumors. Its function has to be investigated in future studies.     

Expression of the coiled coil domain containing protein 116 in the pancreatic islets and endocrine pancreatic tumors

Aims: Coiled coil domain containing protein 116 (CCDC116) is a product of the gene coiled coil domain containing 116 located on human chromosome 22. Its function has not yet been established. The present study focuses on the expression of this protein in human pancreatic islets and in the endocrine pancreatic tumors (EPTs). Methods and Results: Expression of the protein was evaluated by immunohistochemistry in endocrine pancreas from six patients and in various EPTs from 51 patients. In pancreatic islets, virtually all insulin, approx. 75% of the somatostatin, and approx. 60% of the pancreatic polypeptide (PP) cells were immunoreactive for the CCDC116 protein whereas glucagon, ghrelin and the exocrine cells were not. All insulinomas, gastrinomas, non-functioning sporadic tumors and the hereditary multihormonal EPTs were immunoreactive with variable relative incidence. Two of the three somatostatinomas, and one of the three ACTH-secreting tumors also expressed CCDC116. Conclusions: The CCDC116 protein is expressed in all islet cell types except the glucagon and ghrelin cells. Most of the EPTs also contained CCDC116 protein. These findings suggest that this protein may play some role for the above mentioned endocrine cells and tumors. Its function has to be investigated in future studies.     

Symptomatic pancreatic polypeptide-secreting tumor of the distal pancreas (PPoma)

Our report describes a 46-yr-old woman who presented with watery diarrhea in the presence of multiple endocrine neoplasia type I (MEN I) syndrome. Of various potential pancreatic endocrine hormones, only serum levels of pancreatic polypeptide were elevated. Radiologic imaging failed to identify a pancreatic tumor; her diarrhea was therefore managed with subcutaneous administration of somatostatin. Three years later she developed gallstone pancreatitis with the subsequent development of a pancreatic pseudocyst. At exploration for drainage of the pseudocyst, intraoperative ultrasound identified a 6-mm tumor in the distal pancreas that was resected. Final pathology documented a pancreatic endocrine tumor with immunohistochemical staining demonstrating the presence of pancreatic polypeptide. The present case illustrates the symptomatology that may be associated with pancreatic polypeptide-secreting endocrine tumors of the pancreas.