Solitary Insulinoma Research Articles

Laparoscopic Enucleation of Insulinomas

Laparoscopic enucleation of insulinomas is safe and effective and is associated with a short hospital stay. Case series identified through retrospective review of medical records. University of California, San Francisco Medical Center, a tertiary care referral hospital. Nine patients with insulinomas that were thought to be suitable for laparoscopic enucleation. Laparoscopic enucleation of solitary insulinomas of the pancreas. Successful enucleation, conversion to open operation, postoperative complications, and duration of hospitalization. Seven of 9 patients had curative laparoscopic enucleations of insulinomas. In the 2 other patients, the laparoscopic approach was converted to an open operation to perform a distal pancreatectomy. All patients were cured. Computed tomography (CT) localized the tumor in 5 of 9 patients; laparoscopic enucleation was successful in all 5. Endoscopic ultrasonography correctly identified the lesions in 2 of 3 patients with nondiagnostic CT scans. Both lesions were successfully enucleated laparoscopically. Postoperative pancreatic fistulas occurred in 7 of 9 patients, but they caused little morbidity. No patient required another operation. Five of 7 patients treated laparoscopically were discharged to home on the first postoperative day. Laparoscopic enucleation was safe and effective. If the lesion was seen on CT, it could be removed laparoscopically. Endoscopic ultrasonography was useful for identifying lesions in patients whose CT scans were nondiagnostic. Pancreatic fistulas were common, but they resolved spontaneously and produced little morbidity. Laparoscopic enucleation resulted in a short hospitalization and rapid recovery for most patients.

Recurrent Hypoglycemic Seizures and Obesity: Delayed Diagnosis of an Insulinoma in a 15 Year-old Boy - Final Diagnostic Localization with Endosonography

Insulinoma in children and adolescents is extremely rare. In adults diagnosis is frequently delayed due to frequent neuropsychiatric symptoms that are misunderstood. Diagnostic localization is sometimes extremely difficult. We present a case of insulinoma with onset of symptoms at the age of 12.5 years. Diagnosis was made very soon after the first symptoms, but diagnostic localization was delayed, since conventional MRI did not reveal the insulinoma. The patient suffered from recurrent hypoglycemic seizures and gained 54 kg in weight until diagnostic localization was made with abdominal MRI, octreotate-PET and finally successful endosonography. A solitary insulinoma in the pancreatic tail was enucleated laparoscopically.

Organic hyperinsulinism and endoscopic surgery

Experience with minimally invasive surgery for organic hyperinsulinism is limited. No criteria for patient selection with special regard to sporadic, hereditary, multiple and malignant tumors have been defined. The estimated success rate of endoscopic surgery was retrospectively calculated by analysing 34 consecutive patients with organic hyperinsulinism operated on by open surgery. A literature search was undertaken to better define indications for endoscopic procedures. Differences in postoperative outcome (morbidity) between endoscopic and open procedures were analysed. Twenty-eight of 31 patients (90%) with solitary insulinomas and one of three patients with multiple insulinomas were correctly localized preoperatively. Twenty-six enucleations (76%) and eight distal resections (24%) including one endoscopic tail resection were performed. Theoretically only 14 out of 34 patients (41%) would have been suitable for endoscopic surgery (8 enucleations and 6 patients for distal resections which were enucleated using an open approach). Pancreatic fistulas were documented in three patients (9%). Reviewing 34 publications, 49 enucleations, 36 distal resections and 15 conversions to open surgery were performed, showing a higher proportion of distal resections in endoscopic surgery. The spleen was preserved in 88% of cases. Fourteen fistulas occurred after enucleations. Only solitary insulinomas localized in the pancreatic tail or superficially in the body or head may be candidates for endoscopic procedures. Patients with multiple insulinomas, MEN-1 syndrome or malignancy should undergo open surgery.

Laparoscopic approach for solitary insulinoma: a multicentre study

Surgical resection of insulinomas is the preferred treatment in order to avoid symptoms of hypoglycaemia. During the past years, advances in laparoscopic techniques have allowed surgeons to approach the pancreas and treat these lesions laparoscopically. We analysed the feasibility, safety, and outcome of patients undergoing laparoscopic resection of insulinomas in a large, retrospective, multicentre study. Thirty-six patients with pancreatic insulinomas were enrolled in this study. All patients were suspected of having solitary insulinomas after preoperative localisation tests and underwent a laparoscopic approach. Patients, operating characteristics and outcome were analysed. Mean patient age was 48 years (range 20-77 years). Insulinomas were localised in the head (n=7), isthmus (n=2), body (n=14) or tail (n=13) of the pancreas before laparoscopic approach. Mean size of the lesions was 15.5 mm (range 4-25 mm). The surgical procedure was enucleation in 19 cases (52%), spleen-preserving distal pancreatectomy in 12 cases (33%), spleno-pancreatectomy in three cases (8%), one duodenopancreatectomy and one central pancreatectomy. Conversion rate was 30%. The reason for conversion in seven patients (63%) was the inability to localise the tumour during the laparoscopic procedure. In six of these cases laparoscopic ultrasonography was not performed. Mean operating time was 156 min (range 50-420 min). Postoperative course was uneventful in 23 patients (64%). Eleven patients (30%) developed specific complications of pancreatic surgery: intra-abdominal abscess (n=6) or pancreatico-cutaneous fistula (n=5). Mean duration of fistulae was 55 days (range 5-130 days) and all the fistulae were dry at follow-up. After a mean follow-up period of 26 months (range 2-87 months), 33 patients (91%) are free of symptoms, and three patients have been lost to follow-up. The laparoscopic approach is safe to treat preoperatively localised insulinoma, with a morbidity rate comparable to that for the open approach. When the tumour is not found during laparoscopy, laparoscopic ultrasonography seems to be the most efficient tool to localise it and probably to prevent conversion.

Insulinoma

More than 90% of insulinomas are benign tumors. Insulinomas cause hypoglycemia and thereby symptoms of neuroglycopenia and catecholamine response. During symptoms, blood glucose levels should be less than 40 mg/dl (less than 2.2 mmol/l), concomitant insulin levels should be ≧6 IU/ml (≧43 pmol/l) and concomitant C-peptide levels ≧0.2 pmol/l. Most insulinomas can be identified intraoperatively by experienced surgeons. Initial therapy consists of administration of frequent meals and/or by glucose infusion. In patients with solitary insulinomas, complete surgical removal of the tumor should be the primary goal. In patients with metastatic insulinomas, symptoms of insulin hypersecretion will only completely disappear after complete resection of all metastases.

Endoscopic ultrasound localization of a solitary insulinoma of pancreatic tail misdiagnosed as epilepsy: case report.

A 17-year-old female patient with features of epilepsy was treated with valproic acid. Two years later, hypoglycemia and hyperinsulinemia appeared. Transabdominal ultrasonography, spiral computed tomography, and indium-111 Octreoscan were performed without positive results. Endoscopic ultrasonography identified an oval tumor in the pancreatic tail with a color Doppler hypervascular pattern. Surgical enucleation decreased levels of insulin and C-peptide within 20 min, and the patient became free of symptoms and medications.

Rapid insulin assay for intraoperative confirmation of complete resection of insulinomas

Background. Solitary insulinomas are usually the cause of organic hypoglycemia, whereas 13% to 24% of patients with hyperinsulinemia have multiple tumors or nesidioblastosis. Intraoperative glucose levels confirming complete excision have variable accuracy. Intraoperative insulin levels have been shown to predict operative outcome. The purpose of this study was to establish criteria for predicting operative success by using a new, rapid insulin assay as an intraoperative adjunct. Methods. Eight consecutive patients with organic hypoglycemia underwent pancreatic exploration. With an 8-minute immunochemiluminescent insulin assay, peripheral blood levels were obtained preoperatively, during resection, and at 5-minute intervals after surgical excisions. Operative findings and outcome were compared with intraoperative insulin/glucose ratios (I/G), glucose, and insulin levels. Results. By using the return of insulin levels to normal range and I/G ratios ≤ 0.4 15 minutes after tumor(s) resection as criteria to predict operative success, 6 patients had their outcomes correctly predicted (5 true-positive and 1 true-negative). One patient with nesidioblastosis had a false-negative result. One could not be evaluated because of diazoxide medication. These criteria predicted postoperative absence of hypoglycemia with specificity of 100% and accuracy of 89%. Conclusions. These 8-minute insulin assay and criteria can be a useful adjunct for intraoperative assurance of complete insulinoma resection and prediction of postoperative outcome. (Surgery 2002;132:937-43.)

Combined Use of Calcium Infusion Localization and a Minimally Invasive Surgical Procedure in the Management of Insulinoma

To review our experience with current diagnostic localization techniques and a minimally invasive laparoscopic surgical procedure in the management of insulinoma. We describe five patients with insulinoma, the results of diagnostic studies, and a proposed algorithm for management of this rare tumor. Four female patients and one male patient (age range, 34 to 72 years) underwent supervised fasting (mean duration, 12 hours; range, 3 to 28 hours) to establish the diagnosis of insulinoma. These patients had glucose values that ranged from 38 to 41 mg/dL and associated serum insulin levels of 11.3 to 61 microU/mL. C-peptide values ranged from 3.4 to 11.5 ng/mL, and proinsulin levels (measured in four patients) were 32.9 to 82 pmol/L. These biochemical findings were diagnostic for insulin-mediated hypoglycemia, and the high proinsulin and C-peptide levels, in conjunction with negative results of serum measurements for sulfonylureas, excluded an exogenous source of insulin as the cause of hypoglycemia. Four of the five study patients had nondiagnostic results of noninvasive localization studies and underwent selective arterial injection of calcium with hepatic venous sampling to help localize the insulinomas within the pancreas. This procedure correctly localized the lesion in three patients and was associated with no complications. In all five patients, surgical resection of a solitary insulinoma (with use of laparoscopic procedures in four, one of which was converted to an open procedure) yielded resolution of the hypoglycemia. The combination of calcium infusion localization and a minimally invasive surgical procedure is an efficient management approach in the diagnosis and treatment of insulinoma.

Videolaparoscopic resection of insulinomas: experience in two institutions.

Laparoscopic resection of islet cell tumors has been performed in some selected cases. The aim of the study was to analyze the experience of two institutions in the laparoscopic management of insulinomas. In a 4-year period, videolaparoscopic resection of sporadic insulinomas was performed in 9 patients. All patients had hypoglycemia/hyperinsulinism and a solitary tumor demonstrated by image studies. Demographics, surgical findings, results, and complications were analyzed. Mean age of the patients was 43 years. One patient was male and eight were females. One tumor was located in the head of the pancreas, 4 in the body, and 4 in the tail. Laparoscopic resection was completed in all patients. Procedures included 4 enucleations and 5 distal pancreatectomies. Pancreatic resection with splenic preservation was achieved in 4 cases. Intraoperative ultrasound was used in 7 patients. Mean size of the tumors was 1.6 cm. All patients became normoglycemic after surgery. Complications included one pancreatic fistula, one pleural effusion, and one peripancreatic fluid collection. All resolved spontaneously. In a follow-up period between 3 and 48 months no evidence of recurrence has been observed. This series supports laparoscopic resection of preoperatively localized benign solitary insulinomas. The operation provides the advantages of minimally invasive surgery and can be safely performed in most cases.

Therapeutic experience of 65 cases with organic hyperinsulinism.

The treatment for insulinoma is enucleation or resection, which are associated with various degrees of morbidity, including fistulas, pseudocysts, and necessity for reoperations. We evaluated the outcome of 65 patients operated on for organic hyperinsulinism at an experienced university hospital (Department of Surgery, Heinrich-Heine University, Düsseldorf, Germany) between 1990 and 1998. Procedures included enucleation (n=37), left-sided resection (n=19), combination of enucleation from the head and left-sided resection (n=4), subtotal left pancreatectomy (n=2), and pancreaticoduodenectomy (n=3). In 47 out of the 65 patients (72%), the expected benign solitary insulinoma was found. Seven patients had malignant tumors and another eight had multiple tumors (including two with multiple endocrine neoplasia type 1 (MEN-1)), and three had nesidioblastosis. In total, 20 patients (31%) developed postoperative drainage of high amylase containing fluid, which in all but three cases resolved with conservative therapy. The three patients who developed fistulas and the three patients who developed pseudocysts underwent reoperative surgery. Seventeen (41%) of the patients who underwent enucleation (10 from the pancreatic head; 50%) and six (25%) of the resected patients demonstrated these complications. Postoperative glucose metabolism was normalized in all patients. Resection, especially in the head of the pancreas, demonstrates lower complication rates than enucleation. We propose resection for tumors that are large, malignant, situated close to pancreatic duct, and are multiple, including in MEN-1. For tumors in the head, pancreaticoduodenectomy may be an occasional choice.

Endoscopic Ultrasound Localization of a Pancreatic Insulinoma: Case Report and Review of the Localization Techniques

A 23-year-old male was referred to our hospital for evaluation of new-onset seizures. Signs and symptoms of neuroglycopenia, including weakness, dizziness, and confusion, appeared during fasting and resolved promptly with intravenous dextrose administration. Insulin, proinsulin, and C-peptide levels were consistent with a diagnosis of insulinoma. Screening tests for multiple endocrine neoplasia type 1 and surreptitious sulfonylurea uses were negative. Preoperative localization of the insulinoma by transabdominal ultrasonography, computed tomography, and indium-111 octreoscanning were unsuccessful. Endoscopic ultrasonography (EUS) identified a 6- to 7-mm tumor at the juncture of the head and body of the pancreas. Surgical exploration confirmed the preoperative localization, and an 8-mm tumor was simply enucleated. The patient has been free of symptoms for 18 months since surgery. This report describes the utility of EUS to localize a solitary pancreatic insulinoma and provides a comparison of EUS and other preoperative localization techniques.

Insulinoma and islet cell hyperplasia: value of the calcium intraarterial stimulation test when findings of other preoperative studies are negative.

To evaluate the efficacy of the intraarterial calcium test in localizing sources of hyperinsulinism that remain undetectable at preoperative morphologic studies. Twenty-four patients with clinically proved endogenous hyperinsulinism due to tumorous insulin production were prospectively enrolled. They underwent ultrasound (US), computed tomography, magnetic resonance imaging, endoscopic US, abdominal arteriography, and a calcium test, in which insulin concentrations were measured in hepatic venous blood after selective intraarterial calcium stimulation. The results of the calcium test in seven patients (five women, two men; age range, 30-66 years; mean age, 47 years) with negative findings of morphologic studies are described. Six solitary insulinomas (mean diameter, 0.73 cm) and one nodular hyperplasia were diagnosed after surgery. In all seven cases, calcium test findings allowed accurate localization of the pathologic source of insulin secretion. In three of these seven cases, results of arterial calcium stimulation with hepatic venous sampling (ASVS) affected intraoperative management. An increase in insulin concentration after stimulation in the hepatic artery was not observed, making hepatic metastases unlikely. ASVS, which is procedurally simpler than transhepatic pancreatic venous sampling, is effective for localizing sources of hyperinsulinism not detected with preoperative morphologic studies.

TWO CASES OF INSULINOMA OF WHICH LOCATIONS WERE SUCCESSFULLY DETERMINED PREOPERATIVELY

Two cases of insulinoma of which locations were successfully determined preoperatively are reported. Both two patients were admitted to our hospital because of loss of consciousness, and were suspected to have insulinomas by fasting blood sugar levels and blood immuno reactive insuline levels.Ultrasonography, percutaneous transhepatic portal catheterization (PTPC), angiography and dynamic computed tomography showed that the tumors were solitary insulinomas arising in the head of the pancreas. By using intraoperative ultrasonography, the tumors could be removed not to damage the main pancreatic duct. The only curative treatment for the insulinoma is complete excision of the tumor. However, these tumors are often small and some are multiple, in that we have difficulties to determine their locations. Greater efforts using ultrasonography, CT, PTPC, and angiography combinedly would be necessary.

Insulin-Producing Islet Cell Tumors

The types of islet cell pathology and the history and clinical course are presented for 82 patients with proven islet B-cell disease with hyperinsulinism. They form the basis for the recognition of the patient suspected of harboring this syndrome. Among laboratory tests and procedures for recognition of inappropriate hyperinsulinism, the evaluation of plasma levels of glucose (G) and immunoreactive insulin (IRI) on fasting is the most important, with calculation of the IRI/G ratio, if necessary. The determination of the concentration of basal proinsulin and C-peptide is also helpful. Suppression tests and provocative tests are used infrequently. Attempts at preoperative localization are recommended. Ultrasonography and arteriography are helpful, while transhepatic percutaneous portal venous sampling is the only procedure that can differentiate localized (solitary insulinoma) from diffuse hyperinsulinism caused by adenomatosis, hyperplasia, and nesidioblastosis (present in 18% of our patients). Intraoperative ultrasonographic localization may visualize nonpalpable tumors and exclude multiple tumors. Treatment of benign B-cell disease is primarily surgical, but a variety of drugs may be useful for temporary or more prolonged therapy.

Benign pancreatic insulinoma: preoperative and intraoperative sonographic localization.

Twenty-nine patients with surgically proved benign pancreatic insulinoma were studied by preoperative or intraoperative sonography. Twenty-five patients had solitary pancreatic tumors; four had multiple tumors. Six of the patients with solitary insulinomas and one of the patients with multiple insulinomas had undergone previous unsuccessful exploration. Preoperative sonography was performed in 24 patients with solitary insulinomas, and 15 (63%) were localized. Intraoperative sonography was performed in 22 patients with solitary insulinomas, and 19 (86%) were visualized without having been previously located by palpation. Four of these visible solitary tumors (18%) were not detected by palpation at surgery. All the solitary insulinomas were detected with the combination of palpation and intraoperative sonography. In each of the six patients with solitary insulinoma who had undergone previous surgery, the tumor was visible with intraoperative sonography, which also demonstrated nonpalpable insulinomas in two of the four patients with multiple tumors. Preoperative real-time sonography is a sensitive, noninvasive, inexpensive method for localization of insulinoma. Intraoperative high-frequency sonography is a highly sensitive method for the detection of insulinoma. Intraoperative sonography is also valuable to determine the relationship of the insulinoma to pancreatic and bile ducts and thereby facilitate safe enucleation.

Diagnostic monitoring of plasma levels of glucose and insulin during surgery for insulinoma

With serial measurement of blood sugar levels during surgery in three patients with solitary insulinoma, we confirmed the location, then later, the complete elimination of the insulin-secreting tumor. Following vigorous massage of the tumor, blood sugar levels decreased while the levels progressively increased within 20 min following removal of the tumor. Subsequent measurement of simultaneous plasma insulin levels provided further confirmation. Plasma levels of insulin increased in accordance with massage of the tumor. Prior to removal of the tumor, the levels progressively decreased to less than the preoperative levels. For success in detecting slight changes in blood sugar levels secondary to increase or decrease of insulin secretion during surgery for insulinoma, (1) controlled infusion of glucose to keep blood sugar levels around 80 mg/dl and (2) frequent rapid determination of blood sugar levels are considered to be important.