Arterial Stimulation And Venous Sampling Research Articles

LOCALIZATION OF PANCREATIC INSULINOMAS WITH ARTERIAL STIMULATION BY CALCIUM AND HEPATIC VENOUS SAMPLING - PRESENTATION OF A SINGLE CENTRE EXPERIENCE.

Arterial stimulation and venous sampling (ASVS) is the most sensitive diagnostic method for occult insulinoma localization. We present our experience with this method and modifications used that proved to ensure greater safety and sensitivity with this rare pathology. Relationship between tumour size and changes in peak insulin values and release curves were also tested. Six consecutive patients with biochemically established diagnosis of endogenous hyperinsulinism underwent preoperative non-invasive diagnostic tests with sensitivities calculated and compared for all methods. Certain modifications were used in ASVS procedure that included hepatic vein catheterization, order of arterial stimulation, time intervals between each stimulation, diagnostic insulin gradient level and the time frame for diagnostic rise of insulin. Peak insulin values and insulin gradients were compared with tumour size in each patient. In all patients, calcium stimulation accurately localized the insulinoma, with higher sensitivity than any other method. A more than 4-fold increase in insulin level was observed in all patients, after injection into the tumour feeding artery, while 2 to 4-fold increase was observed in the tumour neighbouring areas. Tumour size showed an inversely proportional correlation to peak insulin values in each artery that correctly located the tumour. ASVS presents the most accurate and safe method for localization of occult insulinomas. A four-fold insulin gradient can be used as a limit for positive preoperative localization in order to secure a higher specificity.

Arterial Stimulation and Venous Sampling for Glucagonomas of the Pancreas

Arterial stimulation and venous sampling (ASVS) is a catheter-based diagnostic technique used to identify the localization of an insulinoma or gastrinoma. The aim of this study was to clarify the clinical significance of ASVS for glucagonomas. Eight patients with pancreatic hypervascular tumors and elevated serum glucagon levels in the peripheral blood were enrolled. Pancreatic angiography was performed and a bolus dose of calcium was injected into a suitable artery. Hepatic venous blood samples were then obtained to measure concentrations of glucagon and insulin. All patients underwent surgical resection, and the resected specimens were investigated immunohistochemically. Compared to insulin, the glucagon levels stabilized after calcium stimulation in four patients, with a 1.2-fold increase or decrease. In the remaining four patients, there was a 1.6- to 5.8-fold increase in glucagon levels. The peak value of glucagon was observed at 90s or 120s which was slower than the insulin peak observed in patients with insulinoma. The patients with elevated glucagon levels during ASVS exhibited positive immunostaining of glucagon in resected specimens. Increase in glucagon after calcium stimulation was observed in patients with glucagonomas. ASVS for glucagonomas may be useful in determining the most suitable surgical procedure.

A Case of Proinsulin-Secreting Malignant Insulinoma in an Elderly Patient with Cerebral Infarction

The diagnosis of insulinoma is sometimes challenging and the symptoms of hypoglycemia may be overlooked in elderly patients with cerebrovascular diseases and higher cerebral dysfunction. Recently, there have been an increasing number of case reports of insulinoma secreting proinsulin without hyperinsulinemia. We report a case of proinsulinsecreting malignant insulinoma in a 72-year-old man with aphasia due to cerebral infarction. He manifested no apparent symptoms, although he was incidentally found to have recurrent hypoglycemia by plasma glucose measurements. The Fajans, Grunt and Turner indexes were all within normal range and the arterial stimulation and venous sampling (ASVS) test revealed no increase in insulin concentration. However, proinsulin concentration was markedly elevated (2470 pmol/l) and well-differentiated endocrine adenocarcinoma, malignant insulinoma, with 2 cm in size in the tail of the pancreas was surgically removed. The diagnosis of hypoglycemia requires careful attention especially in elderly persons and/or patients with cerebrovascular diseases. Measurement of proinsulin is recommended in the diagnosis of insulinoma without hyperinsulinemia.

The Usefulness of Super-Selective Computed Tomography Angiography (CTA) for Diagnosing and Localizing a Small Insulinoma

Localization of insulinomas by preoperative imaging is critical for successful surgical resection. However, the visualization and localization of small insulinomas by recent imaging modalities still remains a challenge. Here, we report a 77-year-old woman with a small insulinoma successfully localized by performing arterial stimulation and venous sampling (ASVS), and subsequent super-selective CTA (SSCTA). It was not visualized by routine non-invasive imaging tests such as digital subtraction angiography (DSA). The small size (1.0 cm) of the surgically removed tumor supports the usefulness of SSCTA for localizing very small insulinomas.

Arterial Stimulation and Venous Sampling (ASVS) is Useful for Recurrent Lesions of Insulinoma

We encountered a recurrent case of benign solitary insulinoma in the pancreatic tail, which may have been caused by an inadequate surgical margin in the use of an ultrasonic dissector. A 45-year-old man was referred with hypoglycemia and diagnosed solitary insulinoma in the pancreas. Laparoscopic pancreatic enucleation was performed using an ultrasonic dissector. The tumor was extracted and the surgical margins were microscopically negative. Six years later, he presented with hypoglycemia again. Multiple small well-enhanced lesions were detected by computed tomography distant from the resection stump of the first operation. He underwent resection of all visible lesions with omentum and wide excision of the soft tissue surrounding the pancreas after preoperative arterial stimulation and venous sampling test. The postoperative course of the second operation was uncomplicated and the patient presents no sign of hypoglycemia after 12 months.

低用量の選択的動脈内カルシウム注入法(ASVS)を行い，局在診断が可能であったインスリノーマの2例

低用量の選択的動脈内カルシウム注入法(ASVS)を行い，局在診断が可能であったインスリノーマの2例

Treatment of Hyperinsulinemic Hypoglycemia Due to Diffuse Nesidioblastosis in Adults: A Case Report

An 82-year-old man was admitted to our hospital with a complaint of hypoglycemic syncope in the early morning. Insulinoma was suspected, but an abdominal CT showed no mass. Abdominal angiography showed a slight stain fed from the splenic artery. Arterial stimulation and venous sampling (ASVS) showed an abnormal insulin response only from the splenic artery. Under a provisional diagnosis of insulinoma, surgical treatment was undertaken. Although no pancreatic masses were palpable, we performed a distal pancreatectomy. Subsequently, a pathological examination revealed diffuse nesidioblastosis. Reported cases of diffuse nesidioblastosis have had common clinical features: postprandial hyperinsulinemic hypoglycemia, no abnormal findings in radiological examinations, and the presence of the ductulo-insular complex on histological examination. Surgical resection is recommended, but the extent of surgery is controversial. Our case had some clinical features of insulinoma but was diagnosed as diffuse nesidioblastosis according to histopathologic criteria. Because ASVS showed that the pancreatic body and tail had a lesion producing insulin abnormally, we performed a distal pancreatectomy to cure the hypoglycemia. Clinically, it is very difficult to distinguish diffuse nesidioblastosis from insulinoma. When we treat hyperinsulinemic hypoglycemia, ASVS can be an essential examination to decide the extent of pancreatectomy.

Glucagonoma Diagnosed by Arterial Stimulation and Venous Sampling (ASVS)

To identify the location of pancreatic endocrine tumors, arterial stimulation and venous sampling (ASVS) is known to be useful for insulinoma and gastrinoma, but its usefulness for glucagonoma has not been verified to date. Here we report a case of glucagonoma that was diagnosed by ASVS with calcium loading, in which an approximately 6-fold increase of glucagon was observed in the splenic artery territory. MEN1 gene analysis verified the presence of a mutation and the glucagonoma was confirmed after operation. In conclusion, ASVS could be useful for the diagnosis of glucagonoma.

The Role of Intra-Arterial Calcium Stimulation Test with Hepatic Venous Sampling (IACS) in the Management of Occult Insulinomas

Occult insulinomas remain a clinical challenge. Specifically designed protocols are necessary to aid detection and facilitate a focused pancreatic exploration. Seventeen non-multiple endocrine neoplasia (non-MEN) patients referred to this medical center in the past 10 years because of equivocal diagnosis, failure of previous operation or difficulty in localization for insulinomas were studied. A routine intra-arterial calcium stimulation test with venous sampling (IACS test) was done for lesion localization. An exploratory laparotomy with intraoperative ultrasound (IOUS) examinations was performed. Preoperative imaging (sonography, high-resolution computed tomography scan, and magnetic resonance imaging) found six insulinomas, and IOUS found an additional six in the pancreatic regions; all were compatibly indicated by the IACS test. The remaining five patients with occult lesions by IOUS were treated by 40% (1) or 60-70% (4) distal pancreatectomies when insulin gradients were demonstrated on calcium stimulation to the splenic or to the superior mesenteric artery, respectively, and nesidioblastosis was found in each pathology examination. There were no complications related to the arterial stimulation and venous sampling (ASVS) test. No patient had recurrent hyperinsulinism, permanent morbidity, or mortality from surgery. IACS test helps in the diagnosis of equivocal pancreatogenous hypoglycemia, indicating the pancreatic region of priority exploration and guiding a pancreatic resection.

A Case with Insulinoma Diagnosed and Localized Preoperatively Using Contrast-enhanced Ultrasonography (CEUS) and Arterial Stimulation and Venous Sampling (ASVS)

We report a case with insulinoma diagnosed and localized preoperatively using a combination of contrast-enhanced ultrasonography (CEUS) and arterial stimulation and venous sampling (ASVS). A 76-year-old woman was admitted to our hospital because of hypoglycemic attacks, delirium, and dementia. Fajans' ratio, Grunt's ratio, and Turner's ratio, which are reported to be indexes for endogenous hyperinsulinemia in insulinoma, were all negative. Imaging tests, including computed tomography, magnetic resonance imaging and angiography, failed to detect any abnormalities. CEUS showed a small low echoic lesion in the pancreatic body with blood flow and ASVS showed that the insulin levels in the hepatic vein were extremely increased by calcium injection to the splenic artery, indicating an insulinoma in the pancreatic body preoperatively. An open intra-abdominal operation was performed and an insulinoma was confirmed in the pancreatic body. Enucleation of tumor was undertaken and symptomatic hypoglycemia improved.

Blood glucose control during selective arterial stimulation and venous sampling for localization of focal hyperinsulinism lesions in anesthetized children.

Surgical management of congenital hyperinsulinism is improved by accurate localization of small, focal dysregulated pancreatic lesions using the arterial stimulation and venous sampling (ASVS) test, which can demonstrate increased hepatic venous insulin concentrations after selective arterial injections of calcium. However, anesthesia-related increases in blood glucose can induce insulin secretion, making it difficult to interpret ASVS test data. In this retrospective study, we examined the effect of anesthetic interventions on blood glucose concentrations in 68 children undergoing ASVS testing. We considered only the glucose concentrations observed before calcium stimulation in the final analysis. The choice of drugs for induction (sevoflurane, propofol, or thiopentone), maintenance inhaled anesthetics (sevoflurane, desflurane, or isoflurane), and the use of caudal epidural bupivacaine were not associated with significant differences in the mean blood glucose concentration before ASVS. However, patients receiving remifentanil infusions had smaller mean glucose concentrations (80 +/- 18 versus 100 +/- 44 mg x dl(-1), P = 0.01). These concentrations were also significantly smaller if tracheal intubation was delayed for at least 10 min after induction while patients received inhaled anesthetics via a face mask along with remifentanil infusions (79 +/- 14 for delayed intubation versus 95 +/- 39 mg x dl(-1) for early intubation, respectively, P = 0.03). The percentage increase in glucose concentrations from preintubation values was significantly smaller in these subjects (3.7% +/- 21.9% for delayed intubation versus 31.7% +/- 60.4% for early intubation, P = 0.02). We conclude that the anesthetic management protocol for these patients should include the use of remifentanil infusions and the administration of inhaled anesthetics and remifentanil infusions for a minimum of 10 min to establish a deep plane of anesthesia before tracheal intubation.

Insulin determination by specific and unspecific immunoassays in patients with insulinoma evaluated by the arterial stimulation and venous sampling test

The aim of this study was to compare insulin concentrations measured by a traditional radioimmunoassay (RIA) and a more specific enzyme-linked immunosorbent assay (ELISA) in blood samples obtained during the arterial stimulation and venous sampling (ASVS) test in patients with insulinoma. Prospective case series. In 14 patients with an insulinoma undergoing an ASVS test, blood samples were obtained from the hepatic vein at baseline and 60 s after calcium injection into an artery supplying the tumour and a control artery (supplying pancreatic tissue without tumour). A selective arterial calcium stimulation was performed in five additional patients without evidence for an insulinoma. We measured insulin by a traditional RIA and a specific immunoassay. In patients with insulinoma, insulin concentrations increased between 2.3- and 24.2-fold (median 8.2-fold) when measured by RIA and between 7.3- and 59.4-fold (median 16) when measured by ELISA following calcium injection into the artery supplying the tumour. Following calcium injection into the control artery, insulin concentrations were 0.6 to 1.3 times (median 1.0) the baseline values by RIA and 0.5 to 2.5 times (median 1.1) the baseline values by ELISA. In patients without insulinoma, insulin concentrations increased following calcium stimulation between 0.7- and 2.1-fold (median 1.3-fold) when measured by RIA and between 0.6- and 4.7-fold (median 1.3-fold) when measured by ELISA. When insulin is measured by specific immunoassays, a higher cut-off (i.e. five- to sixfold increase) rather than the traditional criterion of a twofold increase should be used to localise an insulinoma during the ASVS test. The increase in insulin concentrations following calcium stimulation is significantly higher when insulin is measured by a specific assay compared with results obtained with traditional RIAs.

Localization of islet-cell hyperplasia: value of pre- and intraoperative arterial stimulation and venous sampling

Arterial stimulation and venous sampling was effective in the localization of Beta-cell hyperplasia of the pancreas in the islets of Langerhans in an 84-year-old woman. The patient presented with repeated episodes of unconsciousness and hypoglycemia. She was first suspected of having insulinoma, but diagnostic imaging failed to reveal any tumors. Arterial stimulation and venous sampling (ASVS) and percutaneous transhepatic portal venous sampling (PTPS) were performed to localize the tumor. By ASVS, increases in immuno reactive insulin (IRI) were noted in renal vein blood samples (because a splenorenal shunt was present) after splenic arterial stimulation and venous sampling, and PTPS revealed a stepup in IRI from splenic venous blood samples. Preoperative diagnosis suggested Beta-cell hyperplasia in the pancreas tail. Intraoperative ultrasound failed to find a tumor. Intraoperative ASVS showed the site of increase IRI as the pancreas tail, so distal pancreatectomy and splenectomy were performed. However, hypoglycemia was observed constantly after this operation. Relaparotomy, causing additional resection, was conducted to confirm the precise location and to remove the residual Beta-cell hyperplasia of the pancreas. At the second resection, the existing part of Beta-cell hyperplasia was confirmed through intraoperative ASVS, and additional resection of the pancreas body and neck was performed. At this time, complete removal of the residual Beta-cell hyperplasia was confirmed through ASVS. The hypoglycemia and impaired consciousness disappeared after the operation, and the patient's blood sugar level was maintained at a normal level. Pathological findings revealed islets of Langerhans hyperplasia extending to 1 cm in the pancreas tail region. We conclude that pre- and intraoperative ASVS is a useful test for Beta-cell hyperplasia, which is difficult to diagnose through ordinary imaging techniques.

Insulinoma accompanied by diabetes mellitus

A 53-year-old type 2 diabetic man was admitted due to spontaneous relatively hyperinsulinemic hypoglycemia. Oral glucose ingestion and arginine tolerance test showed hyperinsulinemic response. Arterial stimulation and venous sampling (ASVS) showed hyperinsulinemic response measured from the splenic artery after calcium gluconate stimulation. Diagnosis was insulinoma in the pancreas feeding from the artery. He has not suffered from spontaneous hypoglycemia since removal of the pancreatic body, tail and spleen. The specimen showed a solitary islet cell tumor. The high homeostasis model assessment of insulin resistance (HOMA-R) levels reflecting insulin resistance and hyperinsulinemic response after operation remained almost unchanged, indicating high insulin resistance and an insulin hypersecreting diabetic patient.

Evaluation of preoperative and intraoperative arterial stimulation and venous sampling for diagnosis and surgical resection of insulinoma.

The precise intraoperative localization of insulinoma is essential for successful surgical treatment. In addition to various imaging modalities developed recently, arterial stimulation and venous sampling (ASVS) has also been used for tumor localization. Preoperative and intraoperative ASVS procedures were performed in 6 patients with insulinoma. Intraoperative ASVS was performed before and after tumor resection. Immunoreactive insulin (IRI) concentrations and the IRI ratio (IRI concentration at each time interval after calcium injection/baseline IRI concentration) were determined by the conventional or a quick IRI method. The site of the tumor was identified preoperatively in all patients. The peak of the IRI ratio varied widely, but setting the cutoff value at 3.0 clearly differentiated peak IRA ratios in feeding arteries from those of nonfeeding arteries. Intraoperative ASVS showed a similar elevation of IRI levels, but the elevation disappeared after tumor resection in all but 1 patient. In 2 patients, resection of the tumor was confirmed during surgery by measuring IRI levels by the quick IRI method. A combination of ASVS and conventional imaging modalities is useful for precise localization of insulinoma. Resection of the tumor can be confirmed intraoperatively by comparing IRI levels associated with preoperative and postresective ASVS.