Curative resection of multiple gastrinomas aided by selective arterial secretin injection test and intraoperative secretin test.

Recently a number of surgeons have recommended radical resection of gastrinomas in Zollinger-Ellison syndrome (ZES). We have developed a useful technique for preoperative localization of gastrinomas--the selective arterial secretin injection test (SASI)--and we recommend an intraoperative secretin test (IOS) for deciding the radicality of resection of gastrinomas. Here the results of SASI and IOS tests in 11 patients with ZES are examined and compared with the results of other techniques. The SASI test localized gastrinomas in all of the patients, while the sensitivity of ultrasonography, computed tomography, arteriography, or portal venous blood samplings was between 1/11 and 5/11. On the basis of the results of the SASI test, radical resection of gastrinoma was performed in four patients (three pancreatoduodenectomies and one extirpation). After pancreatoduodenectomy, immunohistologic study of the specimen revealed multiple microgastrinomas and lymph node metastases in two patients and the coexistence of a microgastrinoma and a gastinoma in one patient. The IOS test was useful in the estimation of the advisability of radicality, and in two patients total gastrectomy was not performed because of the results of the IOS test. These four patients are well and have returned to work, and their serum gastrin levels are below 35 pg/mL. Thus we believe SASI and IOS tests are helpful for planning curative resection of gastrinomas.     

Insulinoma: Selective arterial calcium injection performed to confirm localization and complete resection

A case of insulinoma is reported in a patient in whom selective arterial calcium injection (SACI) tests were performed both to confirm tumor localization before surgery and to confirm complete tumor removal during surgery. An 18-year-old woman with hypoglycemic episodes was diagnosed with an insulinoma in the pancreatic body demonstrated by celiac arteriography. In a preoperative SACI test, calcium was injected into the splenic artery (SpA), gastroduodenal artery (GDA), and superior mesenteric artery (SMA). Serum immunoreactive insulin (IRI) and proinsulin levels were measured in hepatic venous samples. IRI was markedly increased after the injection of calcium into the GDA and SMA, while there was no response in IRI levels when calcium was injected into the SpA. Therefore, no occult insulinoma was revealed in the distal area fed by the SpA, although the presence of insulinoma was uncertain in the proximal pancreas. In the intraoperative SACI test, calcium was injected into the celiac artery. Insulin (determined by enzyme immunoassay) and proinsulin levels were measured in portal venous samples before and after resection of the tumor. After resection, these levels decreased in response to the calcium stimuli, confirming complete removal of the insulinoma. The SACI test was helpful to localize the insulinoma and was useful to confirm the complete removal of the tumor.     

Intravenous calcium injection test is a novel complementary procedure in differential diagnosis for gastrinoma

The current study evaluated efficacy of the intravenous calcium injection test as a new diagnostic approach to clarify the existence of gastrinoma, which often goes undetected with routine testing. Twenty-six patients with hypergastrinemia were studied. For the calcium injection test, blood samples were taken from 12 patients with hypergastrinemia (HG), and three healthy volunteers, and one patient with nonfunctioning endocrine tumor in the pancreas (control). We compared results of the calcium injection test with those of the secretin test and the selective arterial secretagogue injection (SASI) test. The SASI test with secretin was performed in 24 of 26 patients with hypergastrinemia, including 22 of 24 patients with Zollinger-Ellison syndrome (ZES). Accuracy in the diagnosis of tumor localization by the SASI test was 95% (21 of 22) in ZES patients. The secretin test was negative in 3 of 21 patients with ZES (14%). Either the secretin test or the SASI test was positive in 22 of 23 patients (96%). The calcium injection test was administered to 12 patients in the HG group and 4 controls. The HG group showed significantly higher serum gastrin levels than those of the control group in the calcium injection test. Eight of 10 ZES patients (80%) had a positive calcium injection test. We could diagnose gastrinomas in 100% of ZES patients by either the calcium injection test or the secretin test. We have thus confirmed the efficacy of the intravenous calcium injection test in the diagnosis of gastrinoma. The calcium injection test could become an adjunct in the diagnosis of gastrinoma, which often goes undetected with routine testing.     

Changing Treatment Strategy for Gastrinoma in Patients with Zollinger-Ellison Syndrome

We overviewed the recent development of curative surgery for gastrinoma that has been rapidly improved since the development of new localization techniques, especially the selective arterial secretagogue injection test (SASI test) and somatostatin receptor scintigraphy (SRS). A number of new pathological findings of gastrinomas in patients with Zollinger-Ellison syndrome have been accumulated in accordance with the increase of curative resection of gastrinomas, and these new findings also have contributed to the progress of the treatment strategy for grastrinomas.     

Usefulness of selective arterial secretin injection test for localization of gastrinoma in the Zollinger-Ellison syndrome.

Secretin was injected into a feeding or nonfeeding artery of a gastrinoma and blood samples were taken from the hepatic vein (HV) or a peripheral artery (PA) to measure the changes of serum immunoreactive gastrin concentration (IRG). The IRG in the HV rose within 40 seconds and in the PA rose within 60 seconds after the injection of secretin into a feeding artery, but not after secretin was injected into a nonfeeder. These results indicated that secretin directly stimulates a gastrinoma to release gastrin in vivo. The selective arterial secretin injection test (SASI test) was applied in three patients in whom gastrinomas could not be located by computed tomography, ultrasonography, or arteriography, and functioning gastrinomas were located in all three patients. In one patient, malignant gastrinomas in the head of the pancreas and in the duodenum could be resected radically with the help of this test.     

Selective arterial secretin injection test for localization of gastrinoma

We have already shown that gastrinomas release gastrin when stimulated with secretin in vitro. In order to ascertain whether this is true in vivo and whether the reaction is clinically useful in the localization of gastrinomas, secretin was injected into a feeding artery of the gastrinoma in four patients, and blood samples were taken from a peripheral artery (PA) and the hepatic vein (HV) for determination of immunoreactive gastrin (IRG) and immunoreactive insulin (IRI) levels. When secretin was injected into a feeding artery of the gastrinoma, IRG rose within 40 seconds in the HV and within 60 seconds in the PA. When secretin was injected into a nonfeeder, IRG did not rise for 2 min in the PA. This test was performed to two of the postgastrectomized patients and a patient with hypergastrinemia due to atrophic gastritis. In these patients, IRG in the hepatic vein did not rise for two minutes. It was concluded that secretin directly stimulates gastrinomas to release gastrin in vivo and that the selective arterial secretin injection test is helpful in determining the location of the gastrinoma.     

选择性动脉钙刺激后肝静脉血清胰岛素测定用于胰岛素瘤定位的研究

目的 探讨选择性动脉钙刺激后肝静脉血清胰岛素测定(ASVS)术前定位胰岛素瘤的临床应用价值.方法 对2000年5月至2010年6月收治的28例术前行ASVS检查的胰岛素瘤患者的病史资料进行回顾性分析.结果 28例患者中男12例,女16例,均有Whipple三联征表现.手术切除瘤体32枚,78.1%瘤体直径＜20 mm;术后病理均证实为胰岛素瘤,其中26例单发,2例多发.ASVS检查6例肠系膜上动脉出现最高峰值比,9例胃十二指肠动脉出现最高峰值比,6例脾动脉近段出现最高峰值比,6例脾动脉远段出现最高峰值比,1例检查结果阴性.ASVS最高峰比值数值的中位数、平均数分别为8.8倍、14.8倍.ASVS正确定位25例,错误定位2例,1例检查结果阴性,ASVS准确率为89.3%(25/28),高于同组CT、MRI(CT、MRI定位准确率分别为56.5%,60.0%);ASVS敏感度为96.2%,高于同组CT、MRI(CT、MRI敏感度分别为69.6%,75.0%).结论 ASVS术前定位胰岛素瘤较CT、MRI有优势,但ASVS创伤大,应作为CT、MRI等常规影像学检查阴性时定位胰岛素瘤的补充定位手段.

Abstract：

Objective To evaluate the clinical value of selective intra-arterial calcium stimulated venous sampling ( ASVS) for the localization of pancreatic insulinoma preoperatively.Methods The clinical data of 28 insulinoma patients admitted from May 2000 to June 2010 in Ruijin Hospital undergoing selective intra-arterial calcium stimulated venous sampling with diagnosis of insulinomas before surgery were analyzed retrospectively.Results There were 12 males and 16 females.All the patients had Whipple's triad, and with proved insulinomas by postoperative pathology.There were 26 cases of single insulinoma and 2 cases of multiple insulinomas with altogether 32 insulinomas resected.78.1% of insulinomas were less than 20 mm.All patient were examined by selective intra-arterial calcium stimulated venous sampling.The peak ratio of insulin to the baseline after calcium stimulation appeared at the superior mensenteric artery (SMA) in 6 cases, and the peak ratio of insulin to the baseline after calcium stimulation appeared at gastroduodenal artery(GDA), proximal splenic artery (SAP) and distal splenic artery (SAD) in 9 cases, 6 cases and 6 cases respectively; Selective intra-arterial calcium stimulated venous sampling accurately located 25 cases, and selective intra-arterial calcium stimulated venous sampling located 2 cases wrongly.In one patient, the selective intra-arterial calcium stimulated venous sampling was falsely negative.The mean and median peak ratio of insulin to the baseline after calcium stimulation were 8.8 folds and 14.8 folds respectively.Accurate rate of selective intra-arterial calcium stimulated venous sampling was 89.3% (25/28) and it was higher than that of computed tomography (CT) (56.5% ) , magnetic resonance imaging (MRI) (60.0%).Sensitivity of selective intra-arterial calcium stimulated venous sampling was 96.2%, which was higher than that of computed tomography ( 69.6% ) , magnetic resonance imaging (75.0% ).Conclusion Selective intra-arterial calcium stimulated venous sampling is superior to computed tomography, or magnetic resonance imaging as a preoperative localizing tool for insulinomas, since this procedure is invasive it should be used when other preoperative morphologic studies (computed tomography or magnetic resonance imaging) failed.     

Intra-operative quick insulin assay to confirm complete resection of insulinomas guided by selective arterial calcium injection (SACI)

Background and aims Insulinomas are rare endocrine disorders. Pre-operatively, conventional imaging techniques often fail to localise the tumor. In addition, due to the lack of quick insulin assays, intra-operative confirmation of complete resection was impossible until recently. Materials and methods Six patients with biochemical evidence of an insulinoma underwent pre-operative localisation studies and selective arterial calcium injection (SACI). In addition, insulin was measured before surgery and every 10–15 min after resection of the tumor using a quick insulin assay. Results Pre-operative localisation studies identified the tumor correctly as follows: endosonography: three of four, magnetic resonance imaging: two of four and SACI: six of six. Tumors in the head and body were enucleated while those in the tail were resected (n = 2, each). Those three patients, in whom magnetic resonance imaging and/or endosonography could localise the tumors pre-operatively, underwent laparoscopic surgery while the remaining three patients underwent open surgery. Intra-operatively, insulin dropped to normal levels within 20 min in all cases. After a follow-up of 0.8–3 years, all patients remained biochemically cured. Conclusions Pre-operatively, SACI appears to be a very sensitive localisation technique and may be most helpful in guiding the surgeon if conventional imaging techniques fail to localise the tumor. Complete removal of an insulinoma can be reliably predicted using a quick insulin assay. This paper was presented at the 2nd Biennial Meeting of the European Society of Endocrine Surgeons (ESES), May 18–20, 2006, Krakow, Poland.     

Use of selective arterial secretin injection test to guide surgery in patients with Zollinger-Ellison syndrome

It is often difficult to localize gastrinomas in patients with Zollinger-Ellison syndrome (ZES). We have developed a new useful method, the selective arterial secretin injection test (SASI test), for localizing gastrinomas in patients with ZES. The SASI test first determines the arteries feeding the gastrinomas and then locates the gastrinomas. In 12 patients with ZES, the SASI test clearly localized the gastrinomas, while results obtained with computed tomography or portal venous blood sampling had a positive predictability of less than 10%. Following localization with the SASI test, curative resection of gastrinomas was successfully performed on 7 patients who consented to the operation. Each of 3 patients had one duodenal submucosal microgastrinoma and one or more metastatic lymph node; the other 4 patients had 2 to 10 microgastrinomas or large gastrinomas in the duodenum or the pancreas. All 7 patients, who exhibited negative responses with a postoperative secretin test, have been completely cured from 3 months to 4 years postoperatively. The usefulness of the SASI test for preoperative evaluation is demonstrated by the fact that it gives a 100% positive predictability rate as well as a 100% negative predictability rate. Hence the SASI test precisely locates functioning gastrinomas.

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Resumen Con frecuencia es muy difícil localizar los gastrinomas en pacientes con síndrome de Zollinger-Ellison (SZE). Hemos desarrollado un nuevo y útil método, la prueba de Inyección Arterial Selectiva de Secretina (PIASS), para la localización de gastrinomas en el SZE. La PIASS es un método que primero determina las arterias que nutren los gastrinomas y luego establece su localización. En todos los 12 casos de SZE, la PIASS localizó claramente los gastrinomas, mientras los resultados de la tomografía computadorizada o del muestreo venoso portal exhibieron una predictibilidad positiva de menos del 10%. Luego de la localización de los gastrinomas por la PIASS, se realizó la resección curativa exitosamente en 7 pacientes que dieron su consentimiento para la operación. Cada uno de tres pacientes presentaba un microgastrinoma submucoso duodenal y uno o más ganglios linfáticos metastásicos, y otros cuatro pacientes tenían 2 a 10 micro o grandes gastrinomas en el duodeno o el páncreas. Todos los 7 pacientes presentaron respuestas negativas con la prueba postoperatoria de secretina, y han sido totalmente curados a los 3 meses-4 años después de la operación. La utilidad de la PIASS como examen preoperatorio queda demostrada por el hecho de que provee una predictibilidad del 100% y también por una tasa de predictibilidad negativa de 100%. La PIASS logra la localización preoperatoria precisa de gastrinomas funcionantes.

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Résumé Il est souvent difficile de localiser les gastrinomes responsables d'un syndrome de Zollinger-Ellison (SZE). Nous avons développé une méthode pour localiser ces tumeurs qui consiste à doser la gastrine sanguine après injection sélective de sécrétine par voie artérielle (ISSA). Dans un premier temps, on peut déterminer les artères nourricières de la tumeur, et ensuite localiser la tumeur. Chez 12 patients ayant un SZE, l'ISSA a permis de localiser correctement la tumeur, alors que les investigations traditionnelles par tomodensitométrie ou les dosages dans le sang veineux porte avaient une valeur prédictive positive inférieure à 10%. Après localisation du gastrinome par ce test, la résection curative a été réalisée chez sept patients ayant accepté l'intervention. Trois de ces patients avaient un microgastrinome sousmuqueux du duodénum, avec une ou plusieurs métastases ganglionnaires et quatre patients avaient entre 2 et 10 micro ou macro gastrinomes du duodénum ou du pancréas. Les sept patients avaient tous un test ISSA négatif après l'intervention avec un suivi allant de 3 mois à 4 ans. L'utilité de ce test en préopératoire est démontrée par le fait que les valeurs prédictives positive et négative sont de 100%. Le test ISSA localise avec précision les gastrinomes fonctionnels.

     

A personal experience with pancreatic and duodenal neuroendocrine tumors.

BACKGROUND: Since the concept of hormones was proposed in 1901, numerous gastrointestinal hormones and neuroendocrine tumors that can produce these hormones have been identified. The most common tumors are gastrinomas and insulinomas. STUDY DESIGN: During a 35-year experience, there were 82 neuroendocrine tumors, including 37 gastrinomas, 11 insulinomas, 16 nonfunctioning tumors, 11 gastrinomas suspected but not found, 3 tumors arising in lymph nodes, 1 somatostatinoma, 1 glucagonoma, and 2 amphicrine tumors. MEN I syndrome coexisted with three pancreatic gastrinomas, two pancreatic and duodenal gastrinomas, four suspected gastrinomas, one nonfunctioning tumor, two insulinomas, and no duodenal gastrinomas. RESULTS: Of the nine patients with pancreatic gastrinoma without MEN I, three had lymph node, three had liver metastases, and one had both. The mean survival time was 4.8 years. Three patients with pancreatic gastrinoma and MEN I were alive at 2, 17, and 20 years, respectively. Of the 20 patients with duodenal gastrinoma, none had MEN I; 13 had lymph node metastases and 1 had liver metastases. The overall followup was 7.0 years. Ten patients were biochemically cured. Nonfunctioning tumors, with one exception, originated in the pancreas. Of the three gastrinomas potentially arising in lymph nodes, two, and possibly three, were cured by node removal. Eleven patients had an insulinoma. No patient had recurrence of hypoglycemia after removal of an insulinoma. CONCLUSIONS: Patients with duodenal gastrinoma with lymph node metastases were curable, and cures were achieved occasionally after resection of liver metastases. Results of operation were similar for those with and without MEN I. MEN I and metastases were not contraindications to operation; instead, these patients should be operated on aggressively. Gastrinomas not found at operation were likely to be small duodenal gastrinomas. Gastrinomas can arise in a lymph node and can be cured by its removal. Parietal cell vagotomy is recommended after operation for gastrinomas in the event of residual tumor. With the exception of patients with MEN I or microadenomata, insulinomas were treated best by tumor enucleation. Otherwise, Whipple operation or distal pancreatectomy and enucleation of tumor in the remaining pancreas was indicated.     

Pancreatectomy in multiple endocrine neoplasia type 1-related gastrinomas and pancreatic endocrine neoplasias

OBJECTIVE: The aim of this study was to evaluate the results of pancreatic resection in pancreatic endocrine neoplasias (PENs) in patients affected by multiple endocrine neoplasia type 1 (MEN1) syndrome. BACKGROUND: Since these tumors often show an indolent course, the role of diagnostic procedures and type of surgical approach are controversial. Experience with new diagnostic approaches and more aggressive surgery is still limited. METHODS: Sixteen MEN1 patients were referred to our Surgical Unit (1992-2003) and were operated on for the indications of hypergastrinism, hypoglycemia, and/or pancreatic endocrine neoplasias larger than 1 cm. Zollinger-Ellison syndrome (ZES) was present in 13 patients, 2 of whom experienced a recurrence after previous surgery. Preoperative tumor localization was carried out using ultrasonography (US), computed tomography (CT), endoscopic ultrasonography (EUS), somatostatin receptor scintigraphy (SSRS), or selective arterial secretin injection (SASI). Rapid intraoperative gastrin measurement (IGM) was carried out in 8 patients, and 1 patient also underwent an intraoperative secretin provocative test. RESULTS: Either pancreatoduodenectomy (PD) or total pancreatectomy (TP) or distal pancreatectomy was performed. There was no postoperative mortality; 37% complications included pancreatic (27%) and biliary (6%) fistulas, abdominal collection (6%), and acute pancreatitis (6%). EUS and SSRS were the most sensitive preoperative imaging techniques. At follow-up, 10 of 13 hypergastrinemic patients (77%) are currently eugastrinemic with negative secretin provocative test, while 3 are showing a recurrence of the disease. All patients affected by insulinoma were cured. CONCLUSIONS: MEN1 tumors should be considered surgically curable diseases. IGM may be of value in the assessment of surgical cure. Our experience suggests that PD is superior to less radical surgical approaches in providing cure with limited morbidity in MEN1 gastrinomas and pancreatic neoplasias.     

Intraoperative ultrasonographic localization of islet cell tumors. A prospective comparison to palpation.

The purpose of the present study was to evaluate prospectively the value of intraoperative ultrasound scanning (IOUS) in localizing islet cell tumors by comparing results of IOUS to those of palpation during 44 consecutive laparotomies for gastrinoma (36) or insulinoma (8). All patients had preoperative radiographic imaging studies and selective venous sampling for hormones, which guided the subsequent laparotomy. Any suspicious finding by palpation and/or IOUS was resected. Pathologic evidence of islet cell neoplasm served as the reference standard. Five patients were excluded from analysis because neither palpation nor IOUS had suspicious findings and no islet cell tumor was found. Seven pancreatic insulinomas were found in seven patients. IOUS was as sensitive as palpation at localizing insulinomas. Twenty-three pancreatic gastrinomas were found in 19 patients. IOUS was equal to palpation in the ability to localize gastrinomas. Gastrinomas that were successfully imaged by IOUS were significantly larger than gastrinomas that were not imaged. Twelve extrapancreatic gastrinomas were found in nine patients, and palpation was more sensitive than IOUS at localizing these small duodenal wall tumors. Five patients (11%) had their surgical management changed by IOUS. Two patients had pancreatic tumors (one gastrinoma and insulinoma) enucleated that would not have been found without IOUS, and three patients had resections of pathologically proven malignant islet cell tumors based on sonographic findings. All five patients were cured with short follow-up. The present results demonstrate that palpation and IOUS are complementary because IOUS can image tumors that are not palpable and IOUS can provide additional information concerning malignant potential not detected by palpation.     

Role of 111In-DTPA-pentetreotide scintigraphy in accurate diagnosis of neuroendocrine gastroenteropancreatic tumors

Most gastroenteropancreatic neuroendocrine tumors contain high-affinity binding sites for somatostatin, and somatostatin-receptor scintigraphy has been introduced for the in-vivo evaluation of such tumors. We report two patients with gastroenteropancreatic neuroendocrine tumors, in whom it was quite difficult to localize the tumors by conventional techniques, and in whom we found that ¹¹¹In-pentetreotide scintigraphy was useful for accurate information on tumor localization. In the first patient, who had gastrinoma, multiple tumors were shown in the gastrinoma triangle, but we could not clarify whether there were any tumors in the pancreatic body. The selective arterial secretin injection (SASI) test diagnosed that the gastroduodenal artery was the feeder of the gastrinomas, and ¹¹¹In-pentetreotide scintigraphy with single-photon emission computed tomography indicated the absence of tumors in the pancreatic body. In the second patient, who had insulinoma, multiple liver tumors and a large mass in the hilum of the spleen were shown. ¹¹¹In-pentetreotide scintigraphy was useful in determining that there was no secretion of insulin from the tumor in the hilum of the spleen. In conclusion, X-ray computed tomography is superior for detection of neuroendocrine tumors, because not all neuroendocrine tumors have somatostatin receptors; however, somatostatin receptor scanning, as well as the SASI test, may be useful for the surveillance of patients with known primary tumors, for monitoring patients with disseminated disease, and for following the treatment of these patients. Received: January 9, 2001 / Accepted: July 13, 2001     

31例胰岛细胞瘤诊治的回顾性分析

目的 总结分析胰岛细胞瘤的临床特点,探讨其诊断治疗方法.方法 对湖北医药学院附属太和医院10年间收治的31例胰岛细胞瘤患者的临床特点、诊断和治疗方法进行回顾性分析总结.结果 31例患者中,功能性胰岛细胞瘤占26例,无功能性5例;前者的主要表现为各种各样的低血糖症状,均有典型的Whipple三联征;后者主要是腹部包块就诊...     

Localization and surgical treatment of the pancreatic insulinomas

OBJECTIVES: Insulinomas are rare tumours that originate from the islet cells of the pancreas. The aims of this study were to gain an understanding of the clinical features of insulinomas and to establish the diagnostic and therapeutic strategies. METHODS: A review was carried out in 20 patients with insulinoma surgically treated in our institution over the last 10 years. Presenting symptoms, biochemical studies, preoperative and intraoperative localization studies, operative management and complications were analysed. RESULTS: The male-to-female ratio was 8:12, with a mean age of 46.4 years. Each patient suffered from significant neuroglycopenic symptoms, usually manifested by dizziness, sweating, headache and confusion. The preoperative median serum levels of glucose, insulin and C-peptide at the termination of the fast were 37.5 mg/dL, 23.5 microU/mL, 5.6 ng/mL, respectively. Preoperative tumour localization was achieved by means of ultrasonography (US), computed tomography, selective angiography or intra-arterial calcium injection with hepatic venous sampling, and sensitivities of these examinations were 81.8, 73.7, 94.1 and 100%, respectively. Intraoperative localization was carried out by a combination of manual palpation and intraoperative US with retrospective sensitivities of 80 and 100%, respectively. Enucleation was carried out in 16 patients and distal pancreatectomy in 4. The mortality and morbidity rates were 0 and 10%, respectively. One patient developed late diabetes mellitus type 1 after distal pancreatectomy. CONCLUSIONS: We conclude that the diagnosis of insulinoma can be made on the basis of the results of a supervised fast, careful palpation with intraoperative US is essential for intraoperative detection of insulinomas and surgical resection is the best choice for treatment of benign insulinomas.     

Selective intraarterial methylene blue for pancreatic and duodenal endocrine tumors

Pancreatic and duodenal endocrine tumors can be difficult to localize intraoperatively. Three patients are described in whom selective intraarterial injection of methylene blue was used to correctly identify the position of an endocrine tumor. These patients had a duodenal gastrinoma, a pancreatic polypeptide-producing pancreatic islet cell tumor, and a duodenal somatostatinoma, respectively. Selective arterial secretin injection with hepatic vein gastrin measurement and selective arterial calcium injection with hepatic vein pancreatic polypeptide measurement were used to preoperatively identify the feeding artery. The duodenal somatostatinoma was identified by endoscopy. A catheter placed in the feeding artery just prior to surgery was used for injection of the methylene blue. The combination of selective arterial stimulation and selective arterial methylene blue injection is a promising method for helping surgeons localize elusive endocrine tumors in the duodenum and pancreas.     

Rebound hyperglycemia and peroperative normalization of insulinemia. Complete excision of insulinoma?]

Clinical usefulness of the hyperglycemic rebound and the normalization of plasma insulin level as intraoperative markers of complete removal of insulinoma was assessed. Surgical removal was curative (no clinical or biological recurrence) in six patients harboring a single adenoma (mean follow-up = 32.2 months). In these patients plasma glucose increased an average of 32 mg/dl 30 minutes after resection, 68 mg/dl after 60 minutes, and 91 mg/dl after 90 minutes. Sensitivity of hyperglycemic rebound (defined as a plasma glucose increment of at least 30 mg/dl after tumor removal) as a marker of complete resection of the insulinoma was 40% at 30 min and 83% at 60 minutes after resection. Preresectional values of plasma immunoreactive insulin were elevated in 3 out of 4 patients with adenoma. All postresectional values were within normal ranges. Two patients operated on because of malignant insulinoma, underwent partial tumor resection; hyperglycemic rebound was also present, and high preresectional insulin values became normal 30 minutes after partial tumor removal. We conclude that information provided by intraoperative monitoring of both plasma glucose and insulin cannot be used as the only markers of complete resection of all insulinomas. Only long term clinical and biological follow-up can guarantee the complete resection of an insulinoma.     

胰岛素瘤外科诊断与治疗的变革

Insulinoma is derived from beta cells, and the yearly incidence of insulinoma is 1-4 per one million. Insulinoma patients were often misdiagnosed with epilepsy or cerebrovascular diseases because of the clinical and epidemiological features of insulinoma. The diagnosis of the insulinoma is usually made biochemically with the presence of low blood glucose ( <2.5 mmol/L), elevated insulin ( ≥6 mU/L) and C-peptide levels ( ≥ 200 pmol/L), and no sulfonylureas in the blood.Supervised 72-hour fasting test has been verified as the gold standard in establishing a biochemical diagnosis of insulinoma.Localization of insulinoma is useful for selecting surgical procedures, and the methods for localization can be divided into noninvasive (transabdominal ultrasound, computed tomography,magnetic resonance imaging and endoscopic ultrasound), invasive (angiography and arterial stimulation venous sampling) and intraoperative diagnosis. Surgical treatment is the only curative method at present, and the common approaches include enuclea tion, partial pancreatic resection, resection of the body and tail of pancreas and duodenum-preserving pancreatic head resection.Most patients with sporadic insulinoma had long-term survival after the surgery. For insulinoma patients with multiple endocrine neoplasia type 1, an aggressive surgical approach is recommended.     

Nuclear DNA analysis of insulinomas and gastrinomas

The potential for malignancy of an islet cell tumor of the pancreas is difficult to cytologically judge when one evaluates only the primary lesion, because a malignant condition is usually determined by the presence of regional or distant metastases. Nuclear DNA cytometric measurements have proved helpful both in the evaluation of the malignant potential of other endocrine and nonendocrine lesions and in the determination of the "aggressiveness" of these tumors. Thirty-six islet cell tumors or their metastases from 25 patients were studied. Eleven patients had insulinomas and typical insulinoma syndromes, and 14 others had gastrinomas with the Zollinger-Ellison syndrome. Tissue from each tumor was stained by the Feulgen technique, and nuclear DNA cytometry was performed by means of the microTICAS system designed by the Cytopathology Laboratory of the University of Chicago. Ploidy measurements of insulinomas, taken alone, did not discriminate well between benign and malignant states. However, the single malignant insulinoma could be clearly recognized, for it was one of only two lesions in that group with 5N-exceeding rate (5N-ER) values of 1% or greater. (5N-ER is defined as the percentage of aneuploid nuclei with nuclear DNA content greater than 5N.) On the other hand, seven of eight malignant gastrinomas had ploidy values of 2.5N or greater (our definition of an aneuploid state) and/or had 5N-ER values of 1% or greater, while five of six benign gastrinomas had ploidy values of less than 2.5N and had 5N-ER values of 0%. In addition, the two most aggressive tumors had the highest ploidy and 5N-ER values. Nuclear DNA cytometric studies appear to offer promise as an aid in the evaluation of pancreatic islet cell tumors, particularly gastrinomas.     

Recent advances in treatment of pancreatic neuroendocrine tumors

The recent consensus on the diagnosis and treatment of pancreatic neuroendocrine tumors (PNET) is described. The selective arterial secretagogue injection test and somatostatin receptor scintigraphy are essential for the localization of PNET. A few characteristic clinicopathologic findings of PNET in patients with multiple endocrine neoplasia type 1 (MEN 1) have been elucidated and contributed to improved surgical treatment for these tumors, such as pancreas-preserving total duodenectomy for multiple duodenal gastrinomas in patients with MEN 1 and Zollinger-Ellison syndromes, or distal pancreatectomy for patients with MEN 1 and hypoglycemia. Early diagnosis and early surgical resection of PNET are recommended for complete cure of disease. In liver metastasis of PNET, mass reduction surgery with hepatectomy improves the prognosis of patients, and octreotide LAR has been shown to be useful for reducing complications and inhibiting the growth of tumors.