Surgical treatment of congenital hyperinsulinism

https://doi.org/10.1016/j.sempedsurg.2020.150924Get rights and content

Abstract

A multidisciplinary approach to patients with congenital hyperinsulinism (HI) can distinguish focal from diffuse HI, localize focal lesions, and permit partial pancreatectomy with cure in almost all focal patients. Surgery does not cure diffuse disease but can help prevent severe hypoglycemia and brain damage. Surgery can be curative for insulinoma and for some cases of atypical HI.

Section snippets

Historical background

Evarts Graham performed the first successful pancreatectomy on a child with congenital hyperinsulinism (HI) in 1934 in St Louis, MO. The pancreas was explored searching for an adenoma, but no adenoma was found so a subtotal pancreatectomy was performed and the patient's hypoglycemia resolved.1 This operation was done twenty years before the first description of HI which was termed “syndrome of idiopathic hypoglycemia of infants”.2 It was initially believed that HI was caused by an

Types of hyperinsulinism

Congenital hyperinsulinism is the most common cause of persistent hypoglycemia in neonates and can lead to irreversible brain damage.5 Inappropriate over-secretion of insulin is the hallmark of HI (Fig. 1). Neonates with HI may have diffuse involvement of the pancreatic β-cells (diffuse HI) or focal adenomatous islet cell hyperplasia (focal HI). The focal and diffuse forms of HI are predominantly caused by inactivating mutations of ABCC8 or KCNJ11, the two genes that encode the β-cell

Diagnosis and medical management

The diagnosis of congenital HI was established if fasting hypoglycemia (glucose <50 mg/dL) occurred simultaneously with an inappropriately detectable plasma insulin (>2.0 µU/mL), low plasma beta-hydroxybutyrate (<1.8 mmol/L) and free fatty acids (<1.7 mmol/L), and an inappropriate glycemic response to intravenous glucagon (≥30 mg/dL rise in serum glucose level). Medical therapy to maintain euglycemia was standardized and involved high continuous intravenous infusions of glucose as measured by

Imaging studies

Conventional non-invasive imaging studies such as ultrasound, computerized tomography and magnetic resonance have been used to try to distinguish between focal and diffuse HI and to localize genetically suspected focal lesions without success.13 Invasive interventional tests (Arterial Stimulation with Venous Sampling [ASVS], and Transhepatic Portal Venous Sampling [TPHVS]) were developed in the late 1980s and were used at CHOP until 2004.25,26 These imaging studies take several hours to

Pancreatectomy technique

All operations were approached in a similar manner via a transverse supraumbilical laparotomy.13,23 If a focal lesion has been localized by PET scan, then that portion of the pancreas is exposed first. If diffuse disease is likely or if a suspected focal lesion has not been localized preoperatively, then the pancreas is completely exposed by an extended Kocher maneuver, entry into the lesser sac, and mobilization of the inferior pancreatic border. The pancreas is inspected under 4X loupe

Histopathology

Expert pediatric anatomic pathology interpretation is essential. The biopsies are placed in freezing embedding medium (Cryomatrix, Thermo Shandon, Pittsburgh, PA) and snap frozen. Cryostat sections are fixed in methanol and stained with Hematoxylin and Eosin. After the surgery, all frozen samples are processed for routine histology and immunohistochemistry with confirmation of findings based on paraffin-embedded sections.

The histologic criteria of Rahier33 were used for the diagnosis of the

Postoperative management and follow-up

Postoperative pain after neonatal pancreatectomy is managed by an epidural catheter or intravenous narcotics. Patients are kept NPO until bowel function resumes. The intravenous glucose infusion is re-started immediately after the operation at a very low GIR (2 mg/kg/min) in part because the stress of the surgery induces hepatic glycogenolysis. The GIR is advanced to 5 mg/kg/min 12–18 h after the surgery and to 8 mg/kg/min (equivalent to the physiological hepatic glucose release during fasting

Surgical outcomes by HI type

For the two decade period from 1998 to 2018, we have surgical outcomes for 500 neonates and children who underwent pancreatectomy at CHOP: 246 for focal HI, 202 for diffuse HI, 37 for atypical HI (16 for LINE, 21 for BWS), and 15 for insulinoma.

Focal Hyperinsulinism

There were 246 focal HI patients treated by partial pancreatectomy, including our previously reported 38 patients treated between 1998 and 200313, which was prior to the use of the 18-fluoroDOPA PET/CT scan imaging which began at

Diffuse hyperinsulinism

There were 202 diffuse HI patients, 102 girls and 100 boys. The age of operation ranged from one week to 26 months, with the median age of 6 weeks. 189 diffuse HI patients who failed medical management underwent biopsies to confirm the diagnosis then near-total (98%) pancreatectomy, including five patients who were referred after subtotal pancreatectomy (two were performed laparoscopically) at other hospitals but the patients had severe postoperative hypoglycemia necessitating a near-total

Atypical hyperinsulinism (LINE and BWS)

There were 16 LINE patients. None were diagnosed with LINE preoperatively, molecular genetic testing in peripheral blood was negative in all patients (no KATP or other mutations were identified), and all patients were unresponsive to diazoxide treatment. Compared to focal and diffuse HI patients, the clinical presentation was much later in infancy with a median age of four months. The outcomes were promising after pancreatectomy (range 15 - 95%): ten patients passed a cure fast, and six are

Insulinoma

There were 15 insulinoma patients, and the first 8 insulinoma patients have been reported separately.17 There were 11 boys and 4 girls. The age at operation ranged from 4 to 26 years, with a median age of 11 years. The insulinoma was successfully localized preoperatively in 87% (13/15) of cases after multiple imaging techniques were applied. Abdominal MRI localized the insulinoma in 7/13 patients (54% successful), but abdominal ultrasound (20%), endoscopic ultrasound (22%), CT scan (31%), and

Discussion

Congenital hyperinsulinism is a rare derangement of glucose metabolism, which carries an estimated incidence of 1 to 1.4 in 50,000 live births, leading to an estimated incidence of about 80 new medically-unresponsive cases in the United States each year.37 Subtotal pancreatectomy for management of persistent infantile hypoglycemia was first performed at CHOP in 1950.38 In 1999, we reported a 35 year experience with subtotal (<95%) and near-total (95–98%) pancreatectomy in 53 patients with HI.39

References (47)

  • H.F. McAndrew et al.

    Surgical complications of pancreatectomy for persistent hyperinsulinaemic hypoglycaemia of infancy

    J Pediatr Surg

    (2003)
  • A. Pierro et al.

    Surgical management of congenital hyperinsulinism of infancy

    Semin Pediatr Surg

    (2011)
  • P. Laje et al.

    Pancreatic head resection and Roux-en-Y pancreaticojejunostomy for the treatment of the focal form of congenital hyperinsulinism

    J Pediatr Surg

    (2012)
  • J. Rahier et al.

    Morphologic analysis of focal and diffuse forms of congenital hyperinsulinism

    Semin Pediatr Surg

    (2011)
  • M. Suchi et al.

    Molecular and immunohistochemical analyses of the focal form of congenital hyperinsulinism

    Mod Pathol

    (2006)
  • P. Laje et al.

    Intussusception after pancreatic surgery in children: a case series

    J Pediatr Surg

    (2010)
  • B. Glaser et al.

    ABCC8 mutation allele frequency in the Ashkenzazi Jewish population and risk of focal hyperinsulinemic hypoglycemia

    Genet Med

    (2011)
  • M.A. Anderson et al.

    Endoscopic ultrasound is highly accurate and directs management in patients with neuroendocrine tumors of the pancreas

    Am J Gastroenterol

    (2000)
  • E.P. Tamm et al.

    State-of-the-art imaging of pancreatic neuroendocrine tumors

    Surg. Oncol. Clin. N. Am.

    (2016)
  • S. Al-Shanafey

    Laparoscopic vs open pancreatectomy for persistent hyperinsulinemic hypoglycemia of infancy

    J Pediatr Surg

    (2009)
  • E.A. Graham et al.

    Subtotal resection of the pancreas for hypoglycaemia

    Surg Gynecol Obstet

    (1934)
  • I. McQuarrie

    Idiopathic spontaneously occurring hypoglycemia in infants; clinical significance of problem and treatment

    Am J Dis Child

    (1954)
  • J. Rahier et al.

    Persistent hyperinsulinaemic hypoglycaemia of infancy: a heterogeneous syndrome unrelated to nesidioblastosis

    Arch Dis Child Fetal Neonatal Ed

    (2000)

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    • Laparoscopic Surgery for Focal-Form Congenital Hyperinsulinism Located in Pancreatic Head

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    • The surgical treatment of congenital hyperinsulinism

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    Disclosures: none

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