胰岛素瘤62例诊治体会

目的：总结胰岛素瘤的诊治经验，评估胰岛素瘤的多种定位诊断技术。方法：回顾性分析两院1970年-2001年来收治的62例胰岛素瘤的临床资料。结果：CT、MRI、术前B超、SAOG及IOUS诊断胰岛素瘤的敏感性分别为46.4%、70.0%、75.6%、75.9和100%；手术治疗60例，其中实施肿瘤剜除术41例，胰体尾切除术14例，胰十二指肠切除术3例，楔形切除术1例，姑息手术1例，总手术切除率98.3%；全组无手术死亡，肿瘤切除术后病人随访无低血糖发作；术后并发症包括胰瘘5例、胰腺假性囊肿2例。结论：术前B超和SAOG、术中详尽扪诊联合IOUS可基本上取得胰岛素瘤较为满意的定位诊断；根据胰岛素瘤的大小、部位、数目及性质采取适宜的手术方式是获得良好疗效的关键。     

Endoscopic Ultrasonography for Preoperative Diagnosis and Localization of Insulinomas

Background: Endoscopic ultrasonography (EUS) is generally accepted as a sensitive method for the detection of small pancreatic tumors. We report our experience with EUS for preoperative imaging of insulinomas. Methods: Nine patients with clinical and biochemical signs of insulinoma were examined by EUS using a 7.5/12 MHz radial-scanning ultrasound endoscope prior to surgery. EUS outcome was evaluated on the basis of surgery (open or laparoscopic) and examination of the resected specimens. Results: Two EUS-negative patients appeared, by reassessment of clinical and biochemical data, not to have an insulinoma and were not operated on. EUS correctly imaged and localized five of seven insulinomas that were surgically removed. One isoechoic tumor in the pancreatic head and one pedunculated tumor connected to the caudal side of the pancreatic body were missed by EUS. EUS could demonstrate the size and shape of the imaged tumors, as well as their relationship to adjacent structures, such as the pancreatic duct, bile duct, and large vessels. Conclusions: Our experience with seven insulinomas accords with previous reports claiming EUS to be the method of choice for preoperative imaging and localization of pancreatic islet cell tumors.     

Endoscopic ultrasonography for preoperative diagnosis and localization of insulinomas

BACKGROUND: Endoscopic ultrasonography (EUS) is generally accepted as a sensitive method for the detection of small pancreatic tumors. We report our experience with EUS for preoperative imaging of insulinomas. METHODS: Nine patients with clinical and biochemical signs of insulinoma were examined by EUS using a 7.5/12 MHz radial-scanning ultrasound endoscope prior to surgery. EUS outcome was evaluated on the basis of surgery (open or laparoscopic) and examination of the resected specimens. RESULTS: Two EUS-negative patients appeared, by reassessment of clinical and biochemical data, not to have an insulinoma and were not operated on. EUS correctly imaged and localized five of seven insulinomas that were surgically removed. One isoechoic tumor in the pancreatic head and one pedunculated tumor connected to the caudal side of the pancreatic body were missed by EUS. EUS could demonstrate the size and shape of the imaged tumors, as well as their relationship to adjacent structures, such as the pancreatic duct, bile duct, and large vessels. CONCLUSIONS: Our experience with seven insulinomas accords with previous reports claiming EUS to be the method of choice for preoperative imaging and localization of pancreatic islet cell tumors.     

Determinants of surgical resection for pancreatic neuroendocrine tumors

Pancreatic neuroendocrine tumors (pNETs) include functioning and non‐functional tumors. Functioning tumors consist of tumors that produce a variety of hormones and their clinical effects. Therefore, determinants of resection of pNETs should be discussed for each group of tumors. Less than 10% of insulinomas are malignant, therefore more than 90% of the cases can be cured by surgical resection. Lymphadenectomy is generally not necessary in insulinoma operation. If preoperative localization of the insulinoma is completed, enucleation from the pancreatic body or tail, and distal pancreatectomy can be performed safely by laparoscopy. When preoperative localization of a sporadic insulinoma is not confirmed, surgical exploration is needed. Intraoperative localization of a tumor, intraoperative insulin sampling and frozen section are required. The crucial purpose of surgical resection is to control inappropriate insulin secretion by removing all insulinomas. Gastrinomas are usually located in the duodenum or pancreas, which secrete gastrin and cause Zollinger‐Ellison syndrome (ZES). Duodenal gastrinomas are usually small, therefore they are not seen on preoperative imaging studies or endoscopic ultrasound, and can be found only at surgery if a duodenotomy is performed. In addition, lymph node metastasis is found in 40–60% of cases. Therefore, the experienced surgeons should direct operation for gastrinomas. Surgical exploration with duodenotomy should be performed at a laparotomy. Other functioning pNETs can occur in the pancreas or in other locations. Curative resection is always recommended whenever possible after optimal symptomatic control of the clinical syndrome by medical treatment. Indications for surgery depend on clinical symptom control, tumor size, location, extent, malignancy and presence of metastasis. A lot of non‐functioning pNETs are found incidentally according to the quality improvement of imaging techniques. Localized, small, malignant non‐functioning pNETs should be operated on aggressively, while in possibly benign tumors smaller than 2 cm the surgical risk‐benefit ratio should be carefully weighted. Surgical liver resection is generally proposed in curative intent to all patients with operable metastases from G1 or G2 pNET. The benefits of surgical resection of liver metastases have been demonstrated in terms of overall survival and quality of life. Complete resection is associated with better long‐term survival.     

Genetically-driven or supposed genetic-related insulinomas in adults: validation of the surgical strategy proposed by the A.F.C.E./G.E.N.E.M

Between 1971 and 2002, 80 patients underwent surgery for insulinoma at the Department of General and Endocrine Surgery of the Lille University Hospitals. The present report deals with 13 patients with proven multiple endocrine neoplasia type I (MEN I) or supposed genetic-related insulinomas. This entity differs from spontaneous insulinoma by the presence of multiple foci in the pancreas. Enucleation is not advised in this setting due to the strong likelihood of persistence or recurrence. Various studies suggest different strategies for preoperative localization and surgical approach. We analyzed retrospectively the surgical strategy proposed by the A.F.C.E. and G.E.N.E.M. The purpose of this study was to validate the strategy, integrate the contribution of genotypic diagnosis, simplify preoperative imaging studies, and re-evaluate the value of intraoperative baseline secretin-stimulated insulin measurements. We recommend preoperative endoscopic ultrasonography of the pancreatic head only and routine left pancreatectomy with enucleation of cephalic tumors under intraoperative hormone monitoring. Preoperative invasive localization studies are proposed only if the endoscopic ultrasonography is negative for the pancreatic head. Intraoperative secretin stimulation test can be useful in difficult cases, especially with concurrent nesidioblastosis or in case of secondary surgery. All but one of the 13 patients achieved long-term cure with this strategy.     

彩色多普勒内镜超声在胰岛细胞瘤术前定位诊断中的作用

目的 探讨彩色内镜超声在胰岛细胞瘤术前定位诊断中的作用。方法 对经内科检查定性诊断为胰岛细胞瘤，并准备手术切除的7例患者，术前进行彩色多普勒内镜超声（ECDUS），经腹B超和胰腺螺旋CT增强扫描检查，并与手术和病理检查结果相对照，比较上述3种影像学检查在术前定位诊断中的作用。结果 7例患者手术和病理检查共发现10个病灶，ECDUS检出8个，胰腺螺旋CT增强扫描检出1个，经腹B超未有检出，病灶部位与手术见一致。ECDUS漏诊的2个病灶，直径均小于或等于0.5cm。检查中无并发症发生。结论 ECDUS对胰岛细胞瘤的术前定位诊断比B超，CT等无创性检查技术，敏感性高，定位准确，但对于直径小于或等于0.5cm的病灶，定位诊断仍有困难。     

Contrast-enhanced endoscopic ultrasonography improves the preoperative localization of insulinomas

We report a case in which endoscopic ultrasonography (EUS), intraductal ultrasonography (IDUS) and contrast-enhanced EUS using Levovist helped to localize insulinoma correctly. A 74-year-old woman complained of symptomatic fasting hypoglycemia with relatively high concentration of serum insulin level. Dynamic contrast-enhanced computed tomography revealed a small tumor of 8 mm diameter in the pancreatic head. Insulin secretion was strongly stimulated by calcium injection into the gastroduodenal artery. To clarify the precise localization, we performed EUS, IDUS and contrast-enhanced EUS. The tumor was enhanced clearly by Levovist, and the distance from the main pancreatic duct was more than 3 mm. Therefore, a preoperative decision could be made to use the enucleation method for resection of the tumor. The surgeon could enucleate the tumor in a brief operation according to the preoperative diagnosis, and serum glucose levels returned to normal range after the operation. Contrast-enhanced EUS using Levovist was shown to be a useful diagnostic method for precise localization of small insulinoma.     

Surgical management of insulinoma over three decades

BackgroundThis paper reports our experience of the perioperative management of patients with sporadic, non-malignant, pancreatic insulinoma.MethodsA retrospective monocentric cohort study was performed from January 1989 to July 2019, including all the patients who had been operated on for pancreatic insulinoma. The preoperative work-up, surgical management, and postoperative outcome were analyzed.ResultsEighty patients underwent surgery for sporadic pancreatic insulinoma, 50 of which were female (62%), with a median age of 50 (36–70) years. Preoperatively, the tumors were localized in 76 patients (95%). Computed tomography (CT) and magnetic resonance imaging allowed exact preoperative tumor localization in 76% of the patients (64–85 and 58–88 patients, respectively), increasing to 96% when endoscopic ultrasonography was performed. Forty-one parenchyma-sparing pancreatectomies (PSP) (including enucleation, caudal pancreatectomy, and uncinate process resection) and 39 pancreatic resections were performed. The mortality rate was 6% (n = 5), with a morbidity rate of 72%, including 24 severe complications (30%) and 35 pancreatic fistulas (44%). No differences were found between formal pancreatectomy and PSP in terms of postoperative outcome procedures. The surgery was curative in all the patients.ConclusionCT used in combination with endoscopic ultrasonography allows accurate localization of insulinomas in almost all patients. When possible, a parenchyma-sparing pancreatectomy should be proposed as the first-line surgical strategy.     

Pancreatic insulinoma:current issues and trends

BACKGROUND:Although insulinomas are very rare tumors, they are the most common pancreatic neuroendocrine neoplasms.The incidence in general population is 1-4 per 1 000 000 yearly but the incidence is higher in autopsy studies. The malignancy of insulinomas is difficult to be predicted on the basis of their histological features,and the current WHO classification has been re-evaluated.This review aimed to summarize classical knowledge with current trends in the diagnosis and treatment of insulinomas. DATA SOURCES:A Medline search using terms"insulinoma", "treatment"and"neuroendocrine tumors"was conducted. Additional references were sourced from key articles. RESULTS:Surgery is the treatment of choice for insulinoma and has an extremely high success rate.Medical treatment is also available but only for patients who are unable or unwilling to undergo surgical treatment.Preoperative localization is necessary for planning the surgical approach.Many methods exist for localization of an insulinoma and can be invasive and non-invasive.The combination of biphasic thin section helical CT and endoscopic ultrasonography(EUS)has an almost 100% sensitivity in localizing insulinomas.Laparoscopic ultrasound is mandatory to localize intraoperatively these tumors.EUS-guided fine needle tattoing is an alternative method of localization in case of lack of laparoscopic ultrasound. CONCLUSION:Laparoscopic resection for benign insulinomas is the procedure of choice,whereas pancreatectomy is reserved for large,potentially malignant tumors.     

Occult sporadic insulinoma： Localization and surgical strategy

Insulinomas continue to pose a diagnostic challenge to physicians, surgeons and radiologists alike. Most are intrapancreatic, benign and solitary. Biochemical diagnosis is obtained and imaging techniques to localize lesions continue to evolve. Surgical resection is the treatment of choice. Despite all efforts, an occult insulinoma （occult insulinoma refers to a biochemically proven tumor with indeterminate anatomical site before operation） may still be encountered. New localization preoperative techniques decreases occult cases and the knowledge of the site of the mass before surgery allows to determine whether enucleation of the tumor or pancreatic resection is likely to be required and whether the tumor is amenable to removal via a laparoscopic approach. In absence of preoperative localization and intraoperative detection of an insulinoma, blind pancreatic resection is not recommended.     

Insulinoma: diagnostic strategies and surgical treatment. A 22-year experience.

BACKGROUND/AIMS: The efficacy of preoperative localization methods and the results of the surgical treatment of insulinoma were studied. METHODOLOGY: Fifty-nine patients referred for surgical treatment were studied and the results of the diagnostic tools for tumor localization were compared with findings at surgical intervention. The influence of the type of surgical procedure in the immediate and late postoperative course was also studied. RESULTS: Ultrasonography had a sensitivity of 30%, computed tomography 25%, angiography 54%, portal vein sampling 94%, endoscopic ultrasonography 27% and magnetic resonance 17%. Intraoperative palpation localized 98.2% of the tumors and by the addition of intraoperative echography, all lesions were identified. In 55 patients with benign lesions, 22 enucleations, 25 distal pancreatectomies, 7 pancreatectomies plus enucleation and one duodenopancreatectomy were performed. Malignant tumors were treated by pancreatic resection, postoperative hepatic artery embolization and systemic chemotherapy. There was no postoperative mortality. Pancreatic fistula was the most common complication. Three patients who underwent distal pancreatectomy developed late diabetes (9.3%). CONCLUSIONS: Extensive preoperative investigation, mainly with invasive methods, is not indicated and by combining intraoperative palpation and echography most of the cases can be adequately dealt with. Preservation of pancreatic tissue with enucleation and preservation of the spleen are the best choice for treatment of benign insulinomas.     

Usefulness of selective arterial calcium injection test and secretin test in patients with insulinoma

Preoperatively, it is sometimes very difficult to localize pancreatic endocrine tumors by conventional imaging techniques. Insulinoma is often solitary and benign, but 10% of insulinomas are multiple and malignant. To perform a curative resection of insulinomas, it is important not to leave any tumor postoperatively. In patients with gastrinomas, the selective arterial secretin injection test has been demonstrated to be useful for the curative resection of gastrinomas, since this test tells us whether there is a gastrinoma in the area of interest. The principle of this test is based on the observation that gastrinomas promptly release gastrin when stimulated by secretin. Following a principle analogous to that underlying the secretin test, we have used calcium solution as a stimulant for insulinoma. This selective arterial calcium injection (SACI) test has been used in Kyoto and in National Institute in Health, Bethesda, USA, NIH since 1990. In three patients with insulinoma, curative resection was performed successfully, based on localization by the SACI test. For the differential diagnosis of insulinoma and B cell hyperplasia, we used the intravenous secretin test in 14 patients who had had episodes of hypoglycemia; the test was useful, showing 75% sensitivity and 100% specificity.     

Endoscopic ultrasonography (EUS) in the localization of insulinoma

Objective Endoscopic ultrasonography has been accepted as a sensitive modality for preoperative tumor localization in pancreas. We have aimed to determine the performance characteristics of endoscopic ultrasonography in pancreatic insulinoma localization and evaluation of relationship between the tumor size and serum-c peptide level, lowest glucose level and insulin level. Methods Patients suspicious to insulinoma according to clinical and laboratory findings were included. Endoscopic ultrasonography was performed and if a tumor was identified, the patient was referred for surgery. Results A total of 52 patients (24 male and 28 female) with mean age of 42.4 years underwent EUS and 43 patients underwent surgery. In one patient, a tumor was identified both by transabdominal ultrasonography and abdominal CT scan. The overall sensitivity and accuracy of endoscopic ultrasonography for detection of insulinoma was 89.5% and 83.7% respectively. The sensitivity of endoscopic ultrasonography for detection of lesions in pancreatic head, body and tail was 92.6%, 78.9%, and 40.0%, respectively. There was no relationship between c-peptide, lowest blood glucose, insulin blood levels and tumor size in surgery. Conclusion EUS is an accurate method for detection of insulinoma. The accuracy depends on the location of the tumor and is greatest for tumors in the pancreatic head.     

Surgical aspects of hyperinsulinemic hypoglycemia.

To make a diagnosis of insulinoma, one must consider it. Neuroglycopenic symptoms are the most prominent and convincing, and the combination of hypoglycemia and endogenous hyperinsulinemia are diagnostic of insulinoma. A glucose level of approximately 40 mg/dL with a concomitant insulin level of 6 microU/mL, a C-peptide level exceeding 200 pmol/L, and a negative screening for sulfonylurea must be documented to confirm the diagnosis. Although in the author's experience, preoperative ultrasound is the best and often the only test performed in the patient undergoing a first-time operation, arteriography is perhaps the single most effective localization test performed on a nationwide basis. Expertly performed intraoperative ultrasonography assists in tumor localization and in delineating important related anatomy and has become virtually routine in the author's surgical practice. Insulinomas are typically benign, single, and small, and are generally firmer than surrounding normal pancreas. Extensive surgical exposure may be required to identify and safely remove the tumor. Enucleation is preferred by the author, but distal pancreatectomy for tumors in the body or tail is an excellent method as well. Tumors in the head of the pancreas are usually enucleated, and pancreatoduodenectomy is rarely performed. The most troublesome complication is a pancreatic leakage causing pseudocyst, abscess, or fistula. Except in MEN 1 syndrome, in which a more extensive resection is usually indicated, excision of a single benign insulinoma leads to long-term cure of the disease. The successful excision of an insulinoma will profoundly affect a patient's life.     

Endoscopic ultrasound is highly accurate and directs management in patients with neuroendocrine tumors of the pancreas

Preoperative localization of pancreatic neuroendocrine tumors with traditional imaging fails in 40-60% of patients. Endoscopic ultrasound (EUS) is highly sensitive in the detection of these tumors. Previous reports included relatively few patients or required the collaboration of multiple centers. We report the results of EUS evaluation of 82 patients with pancreatic neuroendocrine tumors. METHODS: We prospectively used EUS early in the diagnostic evaluation of patients with biochemical or clinical evidence of neuroendocrine tumors. Patients had surgical confirmation of tumor localization or clinical follow-up of >1 yr. RESULTS: Eighty-two patients underwent 91 examinations (cases). Thirty patients had multiple endocrine neoplasia syndrome type 1. One hundred pancreatic tumors were visualized by EUS in 54 different patients. The remaining 28 patients had no pancreatic tumor or an extrapancreatic tumor. Surgical/pathological confirmation was obtained in 75 patients. The mean tumor diameter was 1.51 cm and 71% of the tumors were < or =2.0 cm in diameter. Of the 54 explorations with surgical confirmation of a pancreatic tumor, EUS correctly localized the tumor in 50 patients (93%). Twenty-nine insulinomas, 18 gastrinomas, as well as one glucagonoma, one carcinoid tumor, and one somatostatinoma were localized. The most common site for tumor localization was the pancreatic head (46 patients). Most tumors were hypoechoic, homogenous, and had distinct margins. EUS of the pancreas was correctly negative in 20 of 21 patients (specificity, 95%). EUS was more accurate than angiography with or without stimulation testing (secretin for gastrinoma, calcium for insulinoma), transcutaneous ultrasound, and CT in those patients undergoing further imaging procedures. EUS was not reliable in localizing extrapancreatic tumors. CONCLUSIONS: In this series, the largest single center experience reported to date, EUS had an overall sensitivity and accuracy of 93% for pancreatic neuroendocrine tumors. Our results support the use of EUS as a primary diagnostic modality in the evaluation and management of patients with neuroendocrine tumors of the pancreas.     

Pancreatic insulinomas:laparoscopic management

Insulinomas are rare pancreatic neuroendocrine tumors that are most commonly benign,solitary,and intrapancreatic. Uncontrolled insulin overproduction from the tumor produces neurological and adrenergic symptoms of hypoglycemia. Biochemical diagnosis is confirmed by the presence of Whipple's triad,along with corroborating measurements of blood glucose,insulin,proinsulin,C-peptide,β-hydroxybutyrate,and negative tests for hypoglycemic agents during a supervised fasting period. This is accompanied by accurate preoperative localization using both invasive and non-invasive imaging modalities. Following this,careful preoperative planning is required,with the ensuing procedure being preferably carried out laparoscopically. An integral part of the laparoscopic approach is the application of laparoscopic intraoperative ultrasound,which is indispensable for accurate intraoperative localization of the lesion in the pancreatic region. The extent of laparoscopic resection is dependent on preoperative and intraoperative findings,but most commonly involves tumor enucleation or distal pancreatectomy. When performed in an experienced surgical unit,laparoscopic resection is associated with minimal mortality and excellent long-term cure rates. Furthermore,this approach confers equivalent safety and efficacy rates to open resection,while improving cosmesis and reducing hospital stay. As such,laparoscopic resection should be considered in all cases of benign insulinoma where adequate surgical expertise is available.     

Ki-67在胰岛素瘤中的表达及其意义

胰岛素瘤是最常见的胰腺内分泌肿瘤。Ki-67作为一种细胞增殖标志，与多种肿瘤的分化、浸润、转移和预后密切相关。目的：研究Ki-67在胰岛素瘤中的表达情况。探讨其作为胰岛素瘤良恶性鉴别和预后判断标志物的可能性。方法：选取45例胰岛素瘤组织和9例配对瘤旁正常胰腺组织，以免疫组化方法检测Ki-67的表达。并分析其表达与胰岛素瘤临床病理特征的关系。结果：45例胰岛素瘤组织中18例Ki-67表达阳性，阳性率为40．0％，9例配对瘤旁正常胰腺组织均不表达Ki-67。5例（11．1％）胰岛素瘤组织Ki-67指数≥2％。除术前血糖〈2．8mmol／L者Ki-67表达阳性率显著低于术前血糖≥2．8mmol／L者（P=0．025）外，Ki-67表达阳性与否和Ki-67指数与胰岛素瘤的临床病理特征，包括性别、年龄、症状出现至确诊时间、肿瘤原发部位、大小、是否多发、良恶性、有无转移和术后是否治愈均不相关。结论：根据本研究结果尚不能确定Ki-67能作为鉴别胰岛素瘤良恶性和预后判断的标志物。     

Evaluation of the usefulness of percutaneous transhepatic portal catheterization for preoperatively diagnosing the localization of insulinomas.

INTRODUCTION: The precise intraoperative localization of insulinoma is essential for successful surgical management. AIMS: To assess the usefulness of measuring insulin levels by preoperative percutaneous transhepatic portal catheterization (PTPC) and intraoperative ultrasonography (US). METHODOLOGY: PTPC and other preoperative procedures (enhanced computed tomography [CT], arteriography, and US) were performed in eight patients with insulinoma based on our experience during the past 18 years. Intraoperative US was performed in six of the eight patients. RESULTS: PTPC was undertaken in all eight patients, and increased levels of insulin at the sites corresponding to tumors were observed in all patients. Intraoperative US was performed in six patients, which made it possible to detect insulinomas as hypoechoic masses in all of these patients. All tumors were found to exist as single entities. CONCLUSION: PTPC showed the highest diagnostic accuracy in detecting the number of and accurately localizing the tumors before surgery. Meanwhile, all findings from intraoperative US were identical to those of the resection samples, suggesting that this method is a highly reliable examination technique. We conclude that a combination of PTPC and intraoperative US may be essential for the successful surgical management of insulinomas.     

Role of intraoperative ultrasonography in the surgical management of insulinomas

The findings in 35 surgically treated patients with insulinoma and 43 tumors of these patients were analyzed to confirm the efficacy of diagnostic modalities and surgical interventions. The rate of accurate preoperative tumor localization was 72% by angiography, 53% by computed tomographic scan, 55% by ultrasonography, and 83% by percutaneous transhepatic portal vein sampling. Extensive operative exposure and palpation detected 81% of the tumors and intraoperative ultrasonography demonstrated 96% of the tumors. Intraoperative ultrasonography was significantly better than any other diagnostic procedure and was able to demonstrate the anatomical relationship of the insulinoma to the essential structures of the pancreas. Intraoperative ultrasonography also helped determine the safest route for enucleating the insulinomas. Five patients (14%) in our series had metastatic diseases; 2 of these patients with metastases beyond the lymph nodes died due to the growth of tumors. The other 33 patients were free of insulinoma syndrome after the removal of the insulinomas. Streptozotocin was used in 1 patient with recurrent malignant insulinoma, with encouraging results.