Living Donor Liver Transplantation for Congenital Portosystemic Shunt Presenting With Hyperinsulinemic Hypoglycemia.

BACKGROUND: A congenital portosystemic shunt (CPSS) is defined as abnormal vascular communications between the portal vein and the systemic vein. Encephalopathy, hepatopulmonary syndrome, and portopulmonary hypertension are manifestations in patients with CPSS. Hyperinsulinemic hypoglycemia is also one of the manifestations of CPSS. Hyperinsulinemic hypoglycemia secondary to CPSS is caused by a lack of hepatic first-pass elimination of insulin, which is secreted from pancreatic beta cells. CASE PRESENTATION: A 7-month-old boy had hypergalactosemia detected by newborn mass screening. Enhanced abdominal computed tomography showed the absence of the portal vein trunk and extrahepatic portosystemic communication between the superior mesenteric vein and the inferior vena cava. He had suffered from uncontrollable hyperinsulinemic hypoglycemia under protein and lactose restriction. We performed living donor liver transplantation (LDLT) using a left lateral segment graft from his father. The postoperative course was uneventful and the hypoglycemic attacks disappeared. CONCLUSION: We believe that uncontrolled hyperinsulinemic hypoglycemia secondary to CPSS is an indication of LDLT.

Nesidioblastosis and Subsequent Diabetes Mellitus in a Dog with Hyperinsulinemic Hypoglycemia Treated with Partial Pancreatectomy.

A 6.5 yr old castrated male mixed-breed dog was presented for clinical signs associated with hypoglycemia. Hyperinsulinemic hypoglycemia was diagnosed as the cause of the persistent hypoglycemia. No obvious pancreatic mass was seen on abdominal computed tomography and exploratory laparotomy. A partial pancreatectomy was performed with the suspicion of an insulinoma-causing hyperinsulinemic hypoglycemia. Nesidioblastosis was diagnosed based clinical, biochemical, and histopathologic findings. There was beta cell hyperplasia and no evidence of neoplasia. The dog was euglycemic postoperatively after a partial pancreatectomy. Long-term follow-up after 2 yr revealed that the dog was diagnosed with diabetes mellitus.

[Choice of surgical approach to insulin-producing pancreatic tumors]. / Vybor metoda khirurgicheskogo lecheniia insulinprodutsiruiushchikh opukholei podzheludochnoi zhelezy.

AIM: To determine the optimal surgical approach to insulin-producing pancreatic tumors via an analysis of early postoperative results. MATERIAL AND METHODS: There were 134 patients with insulin-producing pancreatic tumors followed by organic hyperinsulinism who have undergone surgery in the faculty-based surgical clinic of the Sechenov First Moscow State Medical University for the period 1990-2017. Patients were divided into three groups depending on type of surgical intervention. Surgical procedure was determined after comprehensive preoperative and intraoperative examination including intraoperative ultrasound. RESULTS: Incidence of postoperative complications was 32.8%. Ten (7.5%) patients required redo surgical interventions. Overall postoperative mortality was 4.5%. The best immediate results were observed in patients undergoing distal pancreatectomy. There was a correlation between incidence of early postoperative complications and tumor location depth in the enucleation group. CONCLUSION: Enucleation is advisable for insulinoma of pancreatic head or uncinated process, as well as superficial tumors of the left half of the pancreas. Distal pancreatectomy is indicated for deep tumors of the left half of the pancreas. Indications for pancreatoduodenectomy are individual.

Long-term incidence of female-specific cancer after bariatric surgery or usual care in the Swedish Obese Subjects Study.

OBJECTIVE: To examine the long-term effects of bariatric surgery on female-specific cancer in women with obesity. METHODS: The prospective, matched Swedish Obese Subjects (SOS) study was designed to examine outcomes after bariatric surgery. This study includes 1420 women from the SOS cohort that underwent bariatric surgery and 1447 contemporaneously matched controls who received conventional obesity treatment. Age was 37-60years and BMI was ≥38kg/m2. Information on cancer events was obtained from the Swedish National Cancer Registry. Median follow-up time was 18.1years (interquartile range 14.8-20.9years, maximum 26years). This study is registered with ClinicalTrials.gov, NCT01479452. RESULTS: Bariatric surgery was associated with reduced risk of overall cancer (hazard ratio=0.71; 95% CI 0.59-0.85; p<0.001). About half of the observed cancers were female-specific, and the incidence of these were lower in the surgery group compared with the control group (hazard ratio=0.68; 95% CI 0.52-0·88; p=0.004). The surgical treatment benefit with respect to female-specific cancer was significantly associated with baseline serum insulin (interaction p value=0.022), with greater relative treatment benefit in patients with medium or high insulin levels. Separate analyses of different types of female-specific cancers showed that bariatric surgery was associated with reduced risk of endometrial cancer (hazard ratio=0.56: 95% CI 0.35-0.89; p=0.014). CONCLUSIONS: In this long-term study, bariatric surgery was associated with reduced risk of female-specific cancer, especially in women with hyperinsulinemia at baseline. FUNDING: This project was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Number R01DK105948 (the content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health), the Swedish Research Council K2013-99X-22279-01, K2013-54X-11285-19, Sahlgrenska University Hospital ALF research grant and Swedish Diabetes Foundation.

Selective Arterial Calcium Stimulation with Hepatic Venous Sampling in Patients with Recurrent Endogenous Hyperinsulinemic Hypoglycemia and Metastatic Insulinoma: Evaluation in Five Patients.

Selective arterial calcium stimulation (SACST) with hepatic venous sampling was performed in 5 patients (3 female, 2 male; age range, 53-73 y) with recurrent endogenous hyperinsulinemic hypoglycemia caused by metastatic insulinoma between January 2004 and December 2014. The biochemical results of SACST confirmed functional hepatic metastases alone (n = 3), peripancreatic lymph-node and hepatic metastases (n = 1), and occult insulinoma in the pancreatic bed (n = 1), thereby helping to guide management. SACST may be useful to determine the extent of functional metastatic insulinoma, particularly within the liver, and may provide clinicians with additional information to help guide the multidisciplinary management of patients with recurrent endogenous hyperinsulinemic hypoglycemia.

Histological insights into the pathogenesis of post-Roux-en-Y hyperinsulinaemic hypoglycaemia.

BACKGROUND: ß-cell hyperplasia has been implicated in the aetiology of post Roux-en-Y gastric bypass hyperinsulinaemic hypoglycaemia, but the pathogenesis of this condition is still unclear. CASE REPORT: We report a case of a 52-year-old man with post-Roux-en-Y gastric bypass hyperinsulinaemic hypoglycaemia who underwent distal pancreatectomy to alleviate his symptoms. Pancreatic histopathology showed chronic pancreatitis with a corresponding loss of exocrine tissue and islet retention. Amyloid deposition was found in pancreatic islets. These features are more typically associated with Type 2 diabetes. DISCUSSION: This case highlights the potential multifactorial pathogenesis of symptomatic hypoglycaemia after Roux-en-Y gastric bypass.

Hypoglycemia mediated by paraneoplastic production of Insulin like growth factor-2 from a malignant renal solitary fibrous tumor - clinical case and literature review.

BACKGROUND: Hypoglycemic episodes are infrequent in individuals without a history of diabetes mellitus or bariatric surgery. When hypoglycemia does occur in such individuals, an uncommon but important diagnosis to consider is non-islet cell tumor hypoglycemia (NICTH). We report a case of NICTH associated with paraneoplastic insulin-like growth factor-2 (IGF-2) production and review current relevant medical literature. CASE PRESENTATION: A 60 year old male with no relevant past medical history was referred to the endocrinology clinic with 18 month history of episodic hypoglycemic symptoms and, on one occasion was noted to have a fingerstick glucose of 36 mg/dL while having symptoms of hypoglycemia. Basic laboratory evaluation was unrevealing. Further evaluation however showed an elevated serum IGF-2 level at 2215 ng/mL (reference range 411-1248 ng/mL). Imaging demonstrated a large right suprarenal mass. A right nephrectomy with resection of the mass demonstrated a malignant solitary fibrous tumor. Post resection, the patient's IGF-2 levels normalized and hypoglycemic symptoms resolved. CONCLUSION: Due to the structural and biochemical homology between IGF-2 and insulin, elevated levels of IGF-2 can result in hypoglycemia. A posttranslational precursor to IGF-2 known as "big IGF" also possesses biologic activity. Review of recent reported cases of NICTH identified widespread anatomic locations and varied pathologic diagnoses of tumors associated with paraneoplastic production of IGF-2 causing hypoglycemia. Definitive management of hypoglycemia associated with paraneoplastic production of IGF-2 consists of resection of the tumor responsible for IGF-2 production. Accumulating literature provides a firm basis for routine IGF-2 laboratory evaluation in patients presenting with spontaneous hypoglycemia with no readily apparent cause.

Endogenous hyperinsulinemic hypoglycemia syndrome: surgical treatment.

BACKGROUND: The endogenous hyperinsulinemic hypoglicemia syndrome (EHHS) can be caused by an insulinoma, or less frequently, by nesidioblastosis in the pediatric population, also known as non insulinoma pancreatic hypoglycemic syndrome (NIPHS) in adults. The aim of this paper is to show the strategy for the surgical treatment of ehhs. MATERIAL AND METHODS: A total of 19 patients with a final diagnosis of insulinoma or NIPHS who were treated surgically from january 2007 until june 2012 were included. We describe the clinical presentation and preoperative work-up. Emphasis is placed on the surgical technique, complications and long-term follow-up. RESULTS: All patients had a positive fasting plasma glucose test. Preoperative localization of the lesions was possible in 89.4% of cases. The most frequent surgery was distal pancreatectomy with spleen preservation (9 cases). Three patients with insulinoma presented with synchronous metastases, which were treated with simultaneous surgery. There was no perioperative mortality and morbidity was 52.6%. Histological analysis revealed that 13 patients (68.4%) had benign insulinoma, 3 malignant insulinoma with liver metastases and 3 with a final diagnosis of SHPNI. Median follow-up was 20 months. All patients diagnosed with benign insulinoma or NIPHS had symptom resolution. CONCLUSION: The surgical treatment of EHHS achieves excellent long-term results in the control of hypoglucemic symptoms.

Refractory idiopathic non-insulinoma pancreatogenous hypoglycemia in an adult: case report and review of the literature.

CONTEXT: Non-insulinoma pancreatogenous hypoglycemia is a rare cause of spontaneous hypoglycemia in adults. The ideal diagnostic and therapeutic approach is still controversial, not least because most reported cases lack long-term follow-up. CASE REPORT: We describe the case of a 58-year-old woman, who was diagnosed with idiopathic non-insulinoma pancreatogenous hypoglycemia in 2001. After resection of 75% of the distal pancreas, she initially experienced no additional hypoglycemic episodes and did not suffer from diabetes mellitus. However, after one month, recurrent hypoglycemia occurred. After resection of the larger part of the remaining pancreatic tissue, the patient suffered from hypoglycemic as well as hyperglycemic episodes. Octreotide and diazoxide were not successful in preventing the hypoglycemic attacks, whereas continuous insulin therapy with an insulin pump helped to stabilize the blood glucose level temporarily. Finally, all remaining pancreatic tissue had to be removed. CONCLUSION: This long-term follow-up of non-insulinoma pancreatogenous hypoglycemia treatment in an adult patient indicates that lateral pancreatectomy may not be sufficient for permanent blood glucose control and emphasizes the need of follow-up data after subtotal pancreatectomy.

[The first experience of endovideosurgical treatment of organic hyperinsulinism].

In connection with the development of endovideosurgical technologies, they are actively used for the treatment of organic hyperinsulinism. The robotized interventions have been applied in the last years. The experience of the laparoscopic and robotized operations performed on 7 patients with established diagnosis of organic hyperinsulinism was shown by the authors. The treatment was effective in all cases. The postoperative period was without complications in majority of patients. An acute postoperative pancreatitis with formation of acute liquid accumulation occurred in one case. This case required the performing of percutaneous puncture interventions using ultrasonics control. Thus, the application of endovideosurgical technologies was accompanied by low percent (14%) of postoperative complications.

[Laparoscopic therapy of organic hyperinsulinism].

The results of laparoscopic treatment were analyzed in 9 patients, suffering pancreatic insulinoma, in the clinic in 2008-2012 yrs. Tumoral enucleation was performed in 6 patients, distal pancreatic resection--in 3. In 1 (11.1%) patient postoperative external pancreatic fistula have developed. All the patients are alive. Laparoscopic treatment of the patients, suffering insulinoma is effective and secure.

[Experience of ASVS-test application in diagnosis of insulin-producing pancreatic tumor].

In 2009-2013 yrs in 7 patients, suffering insulin-producing pancreatic tumors, the ASVS-test was conducted, the result of which was compared with data of standard methods of investigation, including abdominal ultrasound, computer tomography and magnetic resonance imaging. The insuloma enucleation was performed in 3 patients, distal subtotal pancreatectomy with splenectomy--in 1 and the completed total pancreatectomy--in 1. The ASVS-test conduction is indicated in patients with diagnosed hyperinsulinism while impossibility to perform a topic diagnosis of insulinoma, in accordance to data of other noninvasive methods of diagnosis.

Maltodextrin May Be a Promising Treatment Modality After Near-total Pancreatectomy in Infants Younger Than Six Months with Persistent Hyperinsulinism: A Case Report

Persistent hypoglycemia in infants with congenital hyperinsulinism (CHI) can be challenging in approximately half of these cases, even after undergoing a near-total pancreatectomy. While maltodextrin has been recommended in the nutritional management of CHI cases younger than six months, information regarding its efficacy in managing hypoglycemia are not yet clear. Here, we present a male infant with CHI who experienced persistent hypoglycemia even after undergoing a near-total pancreatectomy and despite multiple medical treatments. The infant's hypoglycemic episodes were successfully controlled by adding maltodextrin to his diet.

Non-insulinoma pancreatogenous hypoglycemia syndrome.

We present the case of a 55 yr female who had recurrent severe hypoglycemic attacks with neuroglycopenic symptoms and altered sensorium including coma. The hypoglycemic episodes were not related to fasting. The hypoglycemia was hyperinsulinemic but all imaging modalities for insulinoma were negative. Selective arterial calcium stimulation test localized the lesion to splenic artery territory and distal pancreatectomy left to the splenic vein was done. The histopathology was consistent with nesidioblastosis and gradient guided pancreatectomy relieved the hypoglycemic episodes.

[Prognostic factors of the immediate results of surgical treatment of organic hyperinsulinism].

The clinic obtains the experience of treatment of 245 patients with organic hyperinsulinism. The main goal of the treatment of that category of patients is an improvement of immediate results of surgical treatment which leads to the decrease in mortality level. Authors set the diagnostic and intra- and postoperative treatment algorithm, as well as the major prognostic factors of postoperative morbidity rates. The use of the algorithm allowed the 1,5 decrease in postoperative morbidity and twice decreased the lethality rate.

[Challenges and opportunities for endoscopic ultrasound in the preoperative diagnosis of topical insulin the pancreas].

Insulinoma in most cases is monohormonal orthoendocrine tumor. This fact limits its searching area by a pancreas. However the insulinoma's clinical picture can be caused by other pathology. Therefore the main task of visual the tumor but also to use all the possibilities of each method for defining type of surgery and avoiding such errors and complications, as pancreatorrhage, damage of bile or pancreatic duct, necrosis of duodenal wall, etc. On the basis of our own experience of endoscopic ultrasound for 61 patients with 66 insulinomas, we have allocated the basic variants of insulinoma ultrasound pictures: hypoechoic, heteroechoic, isoechoic tumor, and also foci without a trustworthy contour. On the basis of the analysis of our own errors we have essentially added the technique, having used multiplane pancreas scanning and biplane tumor scanning. Important points in EUS algorithm are also the following items: detecting tumor relationship to pancreatic surface, distance from the tumor to the ducts, gastrointestinal wall and vessels--for definition of possibility of the tumor enucleation; careful scanning of pancreas even after detecting one tumor--for an exception of multiple tumors, especially at MEN-I; careful scanning of a contour of the gland for an exception of parapancreatic insulinomas; estimation of vascularization not only of the detected tumor and suspicious foci, but also of all the gland--for detection of hypervascularized isoechoic tumors; revealing and the description of focal changes, especially more homoechogeneous in comparison with surrounding parenchyma-- for selection patients for examination by other methods; scanning of zones of possible metastasis. Examination of patients with organic hyperinsulinism demands combined application of two or more techniques. Use of all modern possibilities of endosonography can put this technique on one of the first places in the diagnosis of insulinomas.

Case Report: A Difficult-to-Diagnose Case of Hyperinsulinemic Hypoglycemia Surgically Treated After Developing Acute Pancreatitis.

The patient is a 28-year-old Japanese man diagnosed with severe congenital hyperinsulinemic-hypoglycemia six months after birth. Clinical records revealed no imaging evidence of pancreatic tumor at the time of diagnosis. Subsequently, he had developmental disorders and epilepsy caused by recurrent hypoglycemic attacks. The patient's hypoglycemia improved with oral diazoxide. However, he developed necrotizing acute pancreatitis at 28 years of age, thought to be due to diazoxide. Discontinuation of diazoxide caused persistent hypoglycemia, requiring continuous glucose supplementation by tube feeding and total parenteral nutrition. A selective arterial secretagogue injection test revealed diffuse pancreatic hypersecretion of insulin. He underwent subtotal distal (72%) pancreatectomy and splenectomy. There was no intraoperative visible pancreatic tumor. His hypoglycemia improved after the surgical procedure. The histopathological study revealed a high density of islets of Langerhans in the pancreatic body and tail. There were large islets of Langerhans and multiple neuroendocrine cell nests in the whole pancreas. Nests of neuroendocrine cells were also detected in lymph nodes. The pathological diagnosis was grade 1 neuroendocrine tumor (microinsulinomas) with lymph node metastases. This patient is a difficult-to-diagnose case of hyperinsulinemic hypoglycemia surgically treated after developing acute pancreatitis. We believe this is a unique case of microinsulinomas with lymph metastases diagnosed and treated as congenital hyperinsulinemic hypoglycemia for almost 28 years.

Management of postgastric bypass noninsulinoma pancreatogenous hypoglycemia.

INTRODUCTION: Postgastric bypass noninsulinoma hyperinsulinemic pancreatogenous hypoglycemia defines a group of patients with postprandial neuroglycopenic symptoms similar to insulinoma but in many cases more severe. There are few reports of patients with this condition. We describe our surgical experience for the management of this rare condition. METHODS: A retrospective study was performed at St. Vincent Hospital, Indianapolis. Fifteen patients were identified with symptomatic postgastric bypass hypoglycemia for the period 2004-2008. All patients were initially treated with medical therapy for hypoglycemia. Nine patients eventually underwent surgical treatment. The preoperative workup included triple-phase contrast CT scan of the abdomen, endoscopic ultrasound of the pancreas, a 72-h fast followed by a mixed meal test, and calcium-stimulated selective arteriography. Intraoperative pancreatic ultrasound also was performed in all patients. Patients then underwent thorough abdominal exploration, exploration of the entire pancreas, and extended distal pancreatectomy. RESULTS: Nine patients underwent surgery. The mean duration of symptoms was 14 months. The 72-h fast was negative in eight patients (as expected). Triple-phase contrast CT scan of the abdomen was negative in eight patients and showed a cyst in the head of pancreas in one patient. Extended distal (80%) pancreatectomy was performed in all nine patients. The procedure was attempted laparoscopically in eight patients but was converted to open in three. One patient had an open procedure from start to finish. Pathology showed changes compatible with nesidioblastosis with varying degrees of hyperplasia of islets and islet cells. Follow-up ranged from 8-54 (median, 22) months. All patients initially reported marked relief of symptoms. Over time, two patients had complete resolution of symptoms; three patients developed occasional symptoms (once or twice per month), which did not require any medication; two patients developed more frequent symptoms (more than twice per month), which were controlled with medications; and two patients had severe symptoms refractory to medical therapy (calcium channel blockers, diazoxide, octreotide). DISCUSSION: Postprandial hypoglycemia after gastric bypass surgery with endogenous hyperinsulinemia is being increasingly recognized and reported in the literature. Our experience with nine patients is one of the largest. The etiology of this condition is not entirely understood. There may be yet unknown factors involved but increased secretion of glucagon-like peptide 1 and decreased grehlin are being implicated in islet cell hypertrophy. There is no "gold standard" treatment-medical or surgical-but distal pancreatectomy to debulk the hypertrophic islets and islet cells is the main surgical modality in patients with severe symptoms refractory to medical management.