Insulinoma: Diagnosis and surgical treatment. Retrospective analysis of 31 cases.

BACKGROUND : Insulinomas are rare tumors that are usually benign, single and curable by simple surgical excision. They can present problems in diagnosis and localization. STUDY DESIGN: Retrospective analysis of patients with insulinoma managed during a 13-year period (1992-2005) at a tertiary-level institution. RESULTS: 31 patients (mean age 38.4 [SD 13.3] years; 16 men) presented with hypoglycemic symptoms for 4.6 (5.5) years. In 22 (71%) patients, the lesion was successfully localized pre-operatively. Of various pre-operative localization techniques, CT angiography (5/6; 83%), intra-arterial digital subtraction angiography (11/17; 65%), dual-phase CT (8/14; 57%) and conventional MRI (4/13; 31%) had high rates of successful tumor localization. Intra-operative palpation and ultrasonography also had localization success rates (22/30 [76%] and 11/12 [92%], respectively); each identified one lesion that the other procedure did not localize. Of the 30 patients who underwent surgery, 28 had solitary tumor. CONCLUSION: Pre-operative investigations to localize insulinoma are helpful despite the availability of intra-operative ultrasound. Dual-phase CT should be the non-invasive investigation of first choice.     

胰岛素瘤17例临床诊治分析

目的　探讨胰岛素瘤的诊断和治疗方法。　方法　回顾性地分析我院自 196 6年 ～ 2 0 0 0年收治的 17例胰岛素瘤。　结果　胰腺 B超、腹部 CT、选择性腹腔动脉造影检查准确率分别为 82 .4 %、72 .7%、6 0 %。2例未手术 ,15例肿瘤切除。肿瘤位于胰头钩突 3例 ,胰颈 1例 ,胰体尾 11例 ;80 %肿瘤直径 <3cm;行单纯肿瘤摘除术 8例 ,胰体尾切除术 4例 ,胰体尾加脾脏切除者 2例 ,胰腺节段性切除(捆绑式胰体尾空肠吻合空肠端侧吻合术 ) 1例。　结论　血糖、血胰岛素水平测定结合胰腺 B超、CT检查能有效提高功能性胰岛素瘤的诊断。治疗多为单纯性肿瘤切除 ,恶性肿瘤应行根治性切除 ,腹腔镜微创手术正处于尝试阶段 ,药物治疗仍然在探讨阶段。     

Insulinoma

Fundamental to establishing a diagnosis of insulinoma is first to consider the diagnosis when presented with the constellation of symptoms and signs that indicate hypoglycaemia. Prominent and most convincing are manifestations of neuroglycopenia. Although hypoglycaemia can be caused by a number of disorders, the combination of hypoglycaemia and endogenous hyperinsulinaemia is diagnostic of insulinoma. Our criteria now include a glucose level of 40 mg/dl with a concomitant insulin level of 6 μU/ml, a C-peptide level exceeding 200 pmol/l, and negative screen for sulphonlyurea. Ancillary diagnostic tests or the use of insulin surrogates may offer helpful confirmation. Localization is still evolving, but in our hands pre-operative ultrasound is the best and only pre-operative test that we obtain in the usual situation. Expertise and experience with other modalities at other institutions offer reasonable but more costly alternatives. Intraoperative ultrasonography provides significant benefit in both tumour localization and delineating important related anatomy. Insulinomas are virtually all located in the pancreas; 90% are benign, single, and are generally firmer than surrounding normal pancreas. Extensive exposure may be required to identify and remove safely the tumour. Enucleation is our preferred technique, but distal pancreatectomy for tumours in the body or tail is an excellent method as well. Pancreatoduodenectomy is rarely necessary. Complications most commonly relate to leak of pancreatic secretions, causing pseudocyst, abscess, or fistula. Except in MEN 1 syndrome, excision of a benign insulinoma equates with disease cure, and patients are often extraordinarily grateful as the change in their lives may be profound.     

67-jährige Patientin mit rezidivierenden Hypoglykämien

A 67 year old female patient was admitted to our clinic with recurrent hypoglycemia in December 2006. Laboratory findings revealed an elevated insulin, and C-peptide. Imaging techniques revealed a tumor of the pancreas involving the spleen with metastases of the liver, expressing somatostatin receptors. Ultrasound-guided biopsy was performed and confirmed the suspected insulinoma. Since the hypoglycemias could not sufficiently be controlled by subcutaneous administration of octreotide and by oral glucose intake, surgical debulking was performed in a palliative intention. After resection the patient was free of hypoglycemia. In case of diagnosed insulinoma, underlying MEN (multiple endocrine neoplasia) should be considered. Excision of the tumor is recommended in patients with benign solitary insulinomas. If complete excision is impossible, there are several therapeutic options that aim at preventing hypoglycemia. Thus, in contrast to other extended tumors, surgery is reasonable in malignant insulinoma even in case of metastatic disease.     

Insulinoma

Although rare, insulinomas are the most common functioning islet cell tumour of the pancreas. Recognition of the key neuroglycopenic symptoms should trigger the initial investigation. Biochemical proof of endogenous hyperinsulinemic hypoglycemia establishes the diagnosis. Several options are available for imaging and localizing these tumours including ultrasonography, computed tomography, and intra-arterial calcium stimulation with venous sampling. The tumours are usually small, single, benign, well-circumscribed, and evenly distributed throughout the pancreas. This tumour may be a part of the multiple endocrine neoplasia type 1 (MEN-1) syndrome, in which case the tumours are almost always multiple. Surgical treatment is the only curative method, traditionally accomplished with enucleation or partial pancreatic resection. Patients are almost invariably cured lifelong with complete excision of a benign insulinoma. The most recent developments in this area are the recognition of noninsulinoma pancreatogenous hypoglycemia syndrome as a cause of organic hypoglycemia, and the development of laparoscopic techniques to excise these tumours.     

胰腺内分泌肿瘤的外科治疗

目的提高对胰腺内分泌肿瘤的认知和诊疗水平。方法回顾性分析1968～2005年收治的78例胰腺内分泌肿瘤患者的临床资料。结果胰岛素瘤49例，均为良性，其中40例行单纯肿瘤摘除术（2例在腹腔镜下完成），2例在摘除的同时行胰腺空肠Roux—en—Y吻合术，7例行胰体尾切除术；胰高血糖素瘤4例，均有肝转移，行原发病灶及部分转移灶切除术；胰多肽瘤21例，恶性8例，手术切除16例，其余5例因肿瘤无法切除而放弃手术；舒血管肠肽瘤1例和胰腺类癌3例，均为恶性，行外科手术。术后均获得满意的疗效。结论手术切除是胰腺内分泌肿瘤最为理想的治疗方法。术前定性诊断尤为重要，关键是提高对这类肿瘤的认知水平。对胰岛素瘤不强求术前定位诊断，应慎用有创性诊断方法，术中胰腺探查是定位的关键。其他内分泌肿瘤术前多可依影像学检查定位诊断。手术方式根据肿瘤生长部位而定。姑息性切除手术亦可明显缓解症状。即便是恶性肿瘤，其预后亦明显好于胰腺外分泌肿瘤。     

Insulinoma of the pancreas--difficulties with imaging

We present a case of 29-year old man in whom despite the lack of finding tumor in USG and CT surgical intervention was performed and insulinoma of the pancreas was excised. Insulinoma was diagnosed on the basis of clinical picture (Whipple's triade) that was reassured by positive fast test. The fast was terminated at 11 and half hours because of neuroglycopenic symptoms with serum glucose and insulin levels 2.0 mmol/l (36 mg/dl) and 11.07 microU/ml respectively, which established the diagnosis. Laparotomy was performed, during which the tumor was palpated and seen in ultrasonography in the head of pancreas. The tumor of 12 mm diameter was excised. Histopathological examination revealed benign insulinoma. After surgery the symptoms alleviated completely. The patient with proper glucose levels was discharged in good health. The case supports high usefulness of intraoperative ultrasonography and surgeon's palpation.     

Diagnosis value preoperative localization of insulinoma by diffusion-weighted imaging: A pilot study

Insulinoma is the most common functional neuroendocrine tumor that originates from the islet of beta cells. Insulinoma is usually an isolated benign tumor and small in size (<2 cm). Due to the small size of the lesion, it often leads to difficulty in clinical preoperative localization diagnosis. However, we have unexpectedly discovered that the diffusion-weighted-imaging (DWI) adds great value in the preoperative localization diagnosis of insulinoma in non-invasive examination technique.We verified using operative pathology data and retrospectively analyzed the clinical and imageology findings of 5 cases who reported to have an insulinoma. All the 5 cases underwent DWI examination, among non-contrast enhanced magnetic resonance imaging (MRI) in 1 case, contrast-enhanced MRI in 4 cases.Five cases of DWI showed a nodular high signal <1.3 cm with pancreatic tail in 3 cases, pancreatic neck, and pancreatic head in 1 case each, respectively. Non-contrast enhanced MRI showed suspicious abnormal signals in the tail of the pancreas were detected in 1 case. MRI enhanced scans presented 2 cases with abnormal enhancement in the arterial phase and 2 cases without abnormal enhancement in arterial phase. Also, 3 cases showed mild persistence enhanced in the portal venous phase and delayed phase. However, 1 case remained normal in the portal venous phase and the delay period.DWI examination has high clinical value in the localization diagnosis of insulinoma and thus it can be used as a routine examination for preoperative localization diagnosis.     

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.     

Successful laparoscope resection of ectopic insulinoma in duodenohepatic ligament

Both ectopic pancreas and insulinoma are rare. A 21-year-old male patient had suffered from hypoglycemia episodes for 3 years and was diagnosed to have insulinoma based on biochemical and endocrinological evaluations. Various localization approaches revealed a distinct tumor outside the pancreas. With intraoperative endoscopy, the tumor in duodenohepatic ligament was identified and successfully resected. Pathologic evaluation revealed an ectopic insulinoma with ectopic pancreas. Therefore, when the biochemically confirmed insulinoma could not be well-definitely localized, the possibility of ectopic insulinoma should be suspected. In addition, radiography examinations and operation exploration should extend to the field where ectopic pancreas usually presents.     

Intraoperative doppler ultrasound: a reliable diagnostic method in insulinoma

A 44-year-old woman was admitted with obvious symptoms of hypoglycemia and Whipple's triad during a 6-month period. The glucose level was as low as 32 mg/dL and insulin/glucose ratio greater than 0.5 after fasting. Abdominal magnetic resonance imaging (MRI) studies revealed a pancreatic mass at the head, 2 cm in diameter that was not suggesting because of hypointensity. Selective angiography and somatostatin-receptor scintigraphy did not reveal insulinoma. During laparotomy the tumor was palpated on the ventral surface of pancreas and intraoperative ultrasound accurately localized it. Doppler ultrasound examination clearly revealed the hypervascularity of the tumor, which was suggesting an insulinoma. After the tumor enucleation, blood glucose level increased to normal ranges. Histopathological examination revealed benign, well differentiated neuroendocrine tumor, insulinoma. The postoperative recovery was uneventful and the patient is still symptom free during a follow-up period of 6 months. Doppler ultrasound may be a simple but efficient tool for the differential diagnosis of insulinoma. If the clinical symptoms and findings suggest clearly an insulinoma, intraoperative Doppler ultrasound examination seems to be a simple but the most sensitive diagnostic method.     

胰岛细胞瘤的外科诊治经验——附19例报告

目的：探讨胰岛细胞瘤的外科诊断与治疗。方法：回顾分析近5年我院手术的治疗胰岛细胞瘤的经验，总结胰岛细胞瘤临床特征，诊治方法及其效果。结果：本组19例病例中，无功能性胰岛细胞瘤8例，胰岛素瘤11例，其中2例为多发性内分泌瘤瘤，前恶变率62．5％（5／8），平均年龄40岁，后恶变率9．8％（1／11），平均年龄39岁，肿瘤位于胰头8例，胰体6例，胰尾5例，术前影像诊断明确肿瘤定位15例（78．9％），其余4例定位可疑或不能定位经术中超声和触摸探查到定位，对肿瘤行局部切除术11例，胰体尾切除＋胰空肠吻合术5例，肿瘤＋脾脏切除术2例，Whipple手术1例，术后胰瘘发生率为31．6％（6／19），是最常见的并发症，无手术死亡病例。结论：无功能性胰岛细胞瘤恶变率显高于胰岛素瘤（P＜0．01）。术前不能确定肿瘤位置的，应联合应用于中超声和术触摸以探查肿瘤部位。胰岛素瘤手术方式多为单纯肿瘤切除，无功能性胰岛细胞瘤，术中常规冰冻切片检查，对可疑恶性应尽量采取根治性手术。     

Pancreatic insulinomas: diagnosis and treatment

BACKGROUND: Despite its rarity, the insulinoma is the most common pancreatic neuroendocrine tumor. OBJECTIVE: Analyze clinical and immunohistochemical data from surgical resection of the pancreas insulinoma. METHOD: Twelve cases are described, concerning surgical aspects, complications and medium-long term outcome of patients. They underwent surgical treatment due to clinical suspicion and biochemical diagnosis of hypoglycemia and hyperinsulinism. RESULTS: The insulinoma was identified preoperatively in seven patients, while intraoperative ultrasonography and palpation were necessary for diagnosis in the other cases. Eight patients underwent pancreatic resection and pancreatic leak was observed in seven cases. Two patients developed diabetes mellitus and no mortality occurred in the current series. CONCLUSION: All patients presented satisfactory outcome and remained asymptomatic with normal glicemia levels.     

Role of preoperative endoscopic ultrasound-guided fine-needle tattooing of a pancreatic head insulinoma

Although insulinomas are rare, they are the most com-mon pancreatic neuroendocrine tumor, with an inci-dence of four cases per million population. Insulinomas are generally benign indolent intrapancreatic tumors. Surgical resection remains the main option for treat-ment. However, up to 67% of a pancreatic head insu-linomas are nonpalpable, thus surgical resection of the nonplapable insulinoma in this area could become prob-lematic resulting in prolonged surgical time, increased risk of pancreatic duct injury and need for pancreati-coduodenectomy. Endoscopic ultrasound-guided fine- needle tattooing(EUS-FNT), has been shown to have a crucial role for localization of pancreatic body and tail lesions, facilitating laparoscopic distal pancreatectomyand helping surgeons identify the location of the tumor. EUS-FNT might have a role for preoperative localiza-tion of pancreatic head insulinomas which are likely to be nonpalpable. We report a case of preoperative EUS-FNT for localization of a nonplapable pancreatic head insulinoma. This report demonstrates that EUS-FNT of pancreatic head insulinomas may facilitate surgical resection, reduce operative time and decrease surgical complications.     

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.     

Adult-onset diffuse nesidioblastosis causing hypoglycemia

We report the case of a 32-year-old male with adult-onset diffuse nesidioblastosis causing hypoglycemia. Under the tentative diagnosis of insulinoma, localization procedures were carried out but no tumor was found. The presence of an insulinoma in the tail of the pancreas was suggested by selective intra-arterial calcium stimulation with hepatic venous sampling (ASVS). A distal pancreatectomy was performed under the assumed diagnosis of insulinoma in the tail based upon the ASVS. Diffuse nesidioblastosis was diagnosed by histopathological evaluation. During the post-operative course, the patient’s glucose and insulin levels were well controlled and uneventful without any medications or insulin for 7 months.     

Noninsulinoma pancreatogenous hypoglycemia syndrome: a rare case of adult-onset nesidioblastosis

The most common cause of hyperinsulinemic hypoglycemia in adults is insulinoma. Nesidioblastosis is a rare, but well-recognized disorder of persistent hyperinsulinemic hypoglycemia in infancy, but adult-onset nesidioblastosis associated with hyperinsulinemic hypoglycemia, termed noninsulinoma pancreatogenous hypoglycemic syndrome (NIPHS), has been reported. Here, we describe an extremely rare case of NIPHS in an elderly man. A 78-year-old man was admitted to our hospital due to hypoglycemic coma. During the previous 3 months, he noticed excessive sweating at midafternoon. His low fasting plasma glucose level (27 mg/dl) and high immunoreactive insulin level (11.1 muU/ml) were consistent with the possible presence of insulinoma. Localizing studies including computed tomography of the abdomen and celiac arteriography were negative, but selective arterial calcium infusion (SACI) test suggested the presence of insulinoma in the body and tail of the pancreas. Surgical exploration by palpation and intraoperative ultrasonography failed to detect any mass in the pancreas, and 60% distal pancreatectomy was performed. Postoperatively, his hypoglycemic episodes completely disappeared. Histological examination of the resected pancreas revealed diffuse islet cell hyperplasia consistent with a pathological diagnosis of nesidioblastosis. Thus, our case is a very rare case of NIPHS, or adult-onset nesidioblastosis, in which SACI test was proven to be a useful diagnostic tool for localization of the pancreatic lesion.     

Insulinoma: A retrospective study analyzing the differences between benign and malignant tumors

Background/objectives

Insulinoma is a rare pancreatic tumor and, usually, a benign disease but can be a malignant one and, sometimes, a highly aggressive disease. The aim of this study was to determine differences between benign and malignant tumors.

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.     

Un insulinome géant : à propos d’un cas

Islet-cell tumors are the most common neuroendocrine tumors that arise from the endocrine pancreas. They are typically benign and sporadic. Diagnosis is generally established late because clinical signs lack specificity. The insulinoma is difficult to localize since it is very small in size, often not exceeding 2 cm. We report an exceptional case of giant insulinoma initially revealed by a pseudo-polycythemia in an 80-year-old man. He had been treated for hypertension for a few months. Routine biological investigations showed elevated hematocrit and haemoglobin, suggesting Vaquez disease. History taking revealed recent episodes of nocturnal agitation. On admission, he had reddish skin with a suspected enlarged spleen, but total blood volume was normal. Imaging studies showed a voluminous tumor located between the pancreas and the spleen. The presence of an insulinoma was confirmed on the basis of an elevated level of proinsulin at the time of an asymptomatic episode of hypoglycemia. Spleno-pancreatectomy was performed. Histopathological examination revealed a malignant, well-differentiated neuroendocrine malignant tumor.