- Email: [email protected]
Surgical management of congenital hyperinsulinism of infancy
Seminars in Pediatric Surgery (2011) 20, 50-53
Surgical management of congenital hyperinsulinism of infancy Agostino Pierro, MD, PhD, Shireen A. Nah, MRCS, MS From the Department of Paediatric Surgery, UCL Institute of Child Health and Great Ormond Street Hospital for Children, London, United Kingdom. KEYWORDS Hyperinsulinemia; Hypoglycemia; Pancreas; Laparoscopic; Child; Infant
Congenital hyperinsulinism of infancy (CHI) is characterized by inappropriate insulin secretion resulting in persistent hypoglycemia, which can lead to irreversible severe neurological damage in the infant. Many patients with CHI will respond to medical therapy, but surgery is necessary in those that do not. There are 2 main histologic subtypes, diffuse and focal, both of which may require different surgical strategies. Near-total pancreatectomy is the procedure of choice for diffuse CHI, whereas a localized resection is curative in focal CHI. Open surgery is the traditional approach to pancreatic resection. However, laparoscopy is increasingly used, particularly in localized resection for focal disease. We describe both methods of pancreatectomy. © 2011 Elsevier Inc. All rights reserved.
Congenital hyperinsulinism of infancy (CHI) is characterized by inappropriate insulin secretion resulting in persistent hypoglycemia, which can lead to irreversible severe neurological damage in the infant.1 The diagnosis of CHI is based on the following parameters: glucose infusion rate ⬎8 mg/kg/min, laboratory blood glucose ⬍3 mmol/L, detectable insulin/C-peptide, hypoketosis, undetectable/low free fatty acids, and a positive glycemic response to glucagon. Medical therapy is instituted in children with confirmed CHI that consists of a combination of diazoxide (⫾chlorothiazide), nifedipine, and glucagon/octreotide.2,3 Serum biochemical analysis is performed to identify some of the rarer causes of CHI (eg, hyperammonemia). Medically unresponsive children who continue to require intravenous glucose infusion despite maximal medical therapy are treated by pancreatic resection, the extent of which is determined by the histologic type.
Address reprint requests and correspondence: Agostino Pierro, MD, PhD, Department of Paediatric Surgery, Institute of Child Health, 30 Guilford Street, London WC1N 1EH. E-mail address: [email protected]; [email protected].
1055-8586/$ -see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1053/j.sempedsurg.2010.10.009
There are 2 main histologic subtypes: diffuse (60%-70% of patients) and focal (30%-40% of patients).4 To distinguish between diffuse and focal subtypes, a genetic analysis is performed.5 Typically children with diffuse CHI have homozygous recessive or compound heterozygote mutations in the ABCC8 and KCNJ11 genes (which encode the SUR1 and KIR6.2 proteins of the pancreatic beta-cell).5 Focal CHI is associated with loss of heterozygosity for paternally inherited mutations in the Katp genes.6 Children without characteristic genetic mutations of diffuse CHI undergo a 18F-L-3,4-dihydroxyphenylalanine positron emission tomography combined with computed tomography scan (18F-DOPA-PET-CT scan). The PET-CT scan distinguishes between diffuse and focal disease, where diffuse CHI exhibits a diffuse uptake on the PET-CT scan. In focal disease, the scan assists in localizing the site of the focal lesion, allowing a more directed pancreatic resection (Figure 1).7-10 Histologic examination is carried out both intraoperatively and postoperatively. Intraoperative specimens are collected and sent for frozen section analysis. In diffuse CHI, the tail of the pancreas is resected and sent for urgent frozen section histologic analysis to confirm the diagnosis
Pierro and Nah
Surgical Management of CIH of Infancy
51
Open near-total pancreatectomy
Figure 1 18F-DOPA-PET-CT scan, axial view. Greater standardized uptake value indicates a focal lesion. (A) Focal uptake is seen in the head of the pancreas, indicating the presence of a focal lesion. (B) Focal uptake is seen in the tail of the pancreas, indicating the presence of a focal lesion. (Used with permission from the Journal of Pediatric Surgery.) (Color version of figure is available online.)
of diffuse CHI. Further resection only commences when this confirmation has arrived. In focal CHI, the lesion is removed with surrounding normal pancreatic tissue. Intraoperative confirmation of clear resection is essential before the patient is extubated.
The abdomen is accessed via a generous transverse supraumbilical incision. The lesser sac is entered through the gastrocolic omentum; kocherization of the duodenum allows full exposure of the pancreas. The tail of the pancreas is sent for intraoperative frozen section histology and the diagnosis of diffuse CHI is confirmed before proceeding with pancreatectomy. A stay suture is placed in the tail of the pancreas to allow traction of the pancreas facilitating its dissection because direct handling of the pancreas results in fracture of this friable organ. The tail of the pancreas is carefully dissected away from the hilum of the spleen, and the short pancreatic vessels are coagulated. Dissection of the pancreas is carried out in a medial direction towards the head of the pancreas. Pancreatic vessels passing from the splenic vessels into the pancreas are coagulated and divided using bipolar diathermy. Meticulous care is taken with the splenic artery and vein which are closely related to the pancreas, as the spleen should be preserved. Once dissection has arrived at the superior mesenteric vessels, the uncinate process is mobilized. A sling may be placed around the superior mesenteric vessels, retracting them away from the uncinate process. As the head of pancreas is approached, attention is directed to identifying the course of the common bile duct. A sling is placed around the bile duct superior to the first part of the duodenum. A blunt forceps is then passed from within the C-loop of the duodenum behind the first part of the duodenum to grasp the sling, bringing it out superior to the head of pancreas. This becomes the guide to the position of the common bile duct during subsequent dissection of the pancreas. The head of the pancreas is mobilized, and the superior and inferior pancreaticoduodenal vessels are divided. The pancreatic duct is ligated with nonabsorbable sutures and divided. A rim of pancreatic tissue surrounding the common bile duct and along the duodenum is left remaining after near-total pancreatectomy (Figure 2). The abdomen is closed in layers using absorbable sutures. Postoperatively, the patient has both nasogastric tube and bladder catheter. Enteral feeds are restarted after the gastrointestinal function has returned.
Diffuse CHI Most published series agree that that a “near-total” pancreatectomy is required to prevent an unacceptably high incidence of recurrent hyperinsulinemia, with some suggesting that up to a 98% pancreatectomy may be required in refractory cases.11-14 In near-total pancreatectomy, the tail, body, uncinate process and part of pancreatic head are resected, leaving a rim of pancreatic tissue surrounding the common bile duct and along the duodenum (Figure 2). In a 98% pancreatectomy, only small islands of tissue are left along the pancreaticoduodenal arcade bordering the duodenum.15
Figure 2 Near-total pancreatectomy. The shaded area indicates the resected pancreas, leaving behind an amount pancreatic tissue around the common bile duct and along the medial border of the duodenum.
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Seminars in Pediatric Surgery, Vol 20, No 1, February 2011
Laparoscopic near-total pancreatectomy An umbilical 10-mm Hasson port is inserted by an open technique and a 5-mm 30° camera is introduced. Three additional ports are placed: a 5-mm port in the left lower quadrant, a Nathanson retractor at the epigastrium, and a further working port (3 or 5 mm) in the right flank. The gastrocolic omentum is divided and the lesser sac is entered. The Nathanson retractor is used to retract the stomach. The head of the patient is elevated. A stay suture is inserted into the tail of the pancreas which is used to retract the pancreas superiorly. Dissection of the pancreas proceeds towards the head. The short pancreatic vessels passing from the splenic vessels into the pancreas are divided using a 3-mm hook diathermy at very high coagulation settings. These vessels are the most common source of intraoperative hemorrhage, which may be controlled by applying gentle pressure using an atraumatic bowel grasper. The pancreatic tail is transected using the Harmonic Scalpel (Ethicon Endosurgery). The pancreatic tail is removed via the umbilical 10 mm port and sent for frozen section analysis to confirm the diagnosis of diffuse CHI. No further resection takes place until this confirmation has been obtained. Subsequent dissection is facilitated by the insertion of a stay suture at the cut surface of the remaining pancreas which is resected in segments of approximately 2 cm. As dissection nears the head of the pancreas, stay sutures are placed in the uncinate process and the head of pancreas which are retracted superiorly. A neartotal pancreatectomy is achieved by leaving an adequate amount of pancreatic tissue along the medial border of the duodenum where the common bile duct is expected (Figure 2). Port sites are closed using absorbable sutures. No drains are used.
Focal CHI In patients with focal CHI, a localized resection of the focal lesion is curative.3,16 Before surgery, the diagnosis of focal CHI is confirmed by the use of a combination of genetic analysis and findings on 18F-DOPA-PET-CT scan. The site of the lesion seen on PET-CT scan allows preoperative planning of the anticipated procedure. However, it should be noted that the accuracy of localization in PET-CT Scan is approximately 70%.7 In proximal lesions in the head and neck of the pancreas, open resection of the lesion with a small rim of surrounding normal pancreatic tissue is carried out and pancreaticojejunostomy is performed to allow drainage of the distal pancreas. In distal lesions, a distal pancreatectomy may be done laparoscopically (Figure 3).
Figure 3 Focal CHI. (A) Lesion in the head or neck of pancreas (zone A: unshaded area). Surgery: Open excision of focal lesion and pancreaticojejunostomy. (B) Lesion in the body or tail of pancreas (zone B: shaded area). Surgery: Laparoscopic or open distal pancreatectomy.
focal CHI, the lesion is often deep within the parenchyma of the pancreas and may not be visually evident. An intraoperative biopsy is performed for frozen section histologic examination. Histology may reveal the following: (1) the presence of the focal lesion completely resected (normal pancreas at the resection margin); (2) focal lesion not completely resected; (3) the presence of normal pancreas excluding the presence of diffuse CHI and indicating that the focal lesion has not yet been excised.
Focal lesion in head or neck of pancreas When the focal lesion is deep in the head or neck of the pancreas, the procedure may be converted to open and dissection of the head of the pancreas is commenced (Figure 3A). Superficial lesions may be enucleated laparoscopically. A sling may be passed behind the neck of the pancreas to facilitate traction of the pancreas away from the pancreatic bed. Short pancreatic vessels are meticulously ligated using bipolar diathermy and divided. The head of the pancreas is dissected in the direction of the duodenum, carefully avoiding the common bile duct. A pancreaticojejunostomy is then constructed to allow drainage of the distal pancreas.
Focal lesion in body or tail of pancreas In more distal lesions, the entire procedure may be completed either laparoscopically or open (Figure 3B). Once histologic confirmation of focal disease is obtained, the pancreas is dissected as described previously. Dissection is performed until the resected specimen includes the lesion. The pancreas is transacted with the Harmonic Scalpel (Ethicon Endosurgery, Cincinnati, OH). An adequate resection margin is confirmed by further frozen section analysis. There is no need for drains.
Surgery for focal CHI The abdomen is accessed laparoscopically as described previously. The pancreas is inspected and palpated for a nodular area, which indicates the site of the focal lesion. In
Postoperative management Enteral feeds are recommenced as early as the first postoperative day and gradually advanced, reducing the intrave-
Pierro and Nah
Surgical Management of CIH of Infancy
nous infusion of dextrose. It is not unusual to observe a period of gastroparesis, particularly after excision of the head of the pancreas for focal lesions or near-total pancreatectomy for diffuse CHI. This may last 2-3 days. The management of postoperative hypoglycemia may require medical treatment. However, this is usually transient. Further resection of the pancreas is needed when bolus enteral feeding and cessation of continuous intravenous glucose is not achieved.
Complications Several reports have been published on the outcomes and complications of open pancreatectomy.14,17-22 The most serious complications are associated with near-total pancreatectomy and include recurrent hyperinsulinemic hypoglycemia which may require repeat pancreatic resection, biliary tree injury, and pancreatic endocrine and exocrine insufficiency. McAndrew et al20 reported on 48 patients undergoing open near-total pancreatectomy for CHI. There was 1 splenic injury, 1 small bowel injury, and 1 adhesive obstruction. There were 7 patients (15%) who had bile duct injury. Treatment for persistent hyperinsulinism was required in 11 (23%) patients, 9 of whom required further pancreatic resection. Diabetes mellitus was observed in 20 (42%) patients and exocrine deficiency requiring enzyme therapy was present in 13 (27%) patients. In other published series of open pancreatectomy, complications were seen in 8%-21% of patients.14,17-21 Biliary tree injury was reported in all open series with an incidence of 2%-15%. The incidence of further pancreatic resection for persistent CHI ranged from 8% to 33%; the need for medical treatment for persistent hypoglycemia ranged from 0% to 58%. Postoperative diabetes mellitus was seen in 12%-56% of patients, and the need for pancreatic enzyme replacement was 4%-37%. There are few published reports on laparoscopic pancreatectomy for CHI.21,23 Al-Shanafey et al21 reported 12 children who had laparoscopic near-total pancreatectomy. Eight (67%) patients had persistent hypoglycemia, one required further resection and there were no bile duct injuries.
Conclusions The management of CHI is challenging and requires a multidisciplinary approach. Pancreatectomy is necessary when medical therapy fails. Successful surgery is dependent on good preoperative assessment using genetic analysis and PET-CT scan, reliable intraoperative histologic analysis and meticulous surgical technique. The extent of surgery and type of procedure are determined by histology and site of the lesion; this may be a partial pancreatectomy for focal lesions or near-total pancreatectomy for diffuse congenital hyperinsulinism.
53
References 1. De Leon D, Stanley CA. Mechanisms of disease: advances in diagnosis and treatment of hyperinsulinism in neonates. Nat Clin Pract Endocrinol Metab 2007;31:57-68. 2. Kapoor RR, Flanagan SE, James C, et al. Hyperinsulinaemic hypoglycaemia. Arch Dis Child 2009;94:450-7. 3. Hussain K. Diagnosis and management of hyperinsulinaemic hypoglycaemia of infancy. Horm Res 2008;69:2-13. 4. Miyano T. The pancreas. In: Grosfeld JL, et al., eds Pediatric Surgery, 6th edn Philadelphia, PA: Mosby, 2006:1671-90. 5. James C, Kapoor RR, Ismail D, Hussain K. The genetic basis of congenital hyperinsulinism. J Med Genet 2009;46:289-99. 6. Glaser B, Kesavan P, Haymen M, et al. Familial hyperinsulinism caused by an activating glucokinase mechanism. N Engl J Med 1998; 338:226-30. 7. Zani A, Nah SA, Ron O, et al. The predictive value of preoperative 18Fluoro-L-dopa-PET-CT scans in children with congenital hyperinsulinism of infancy. Presented at the 41st Annual Meeting of the American Pediatric Surgical Association. J Pediatr Surg, in press. 8. Ribeiro MJ, De Lonlay P, Delzescaux T, et al. Characterization of hyperinsulinism in infancy assessed with PET and 18-F-fluoro-L-dopa. J Nucl Med 2005;46:560-6. 9. Otonkoski T, Nanto-Salonen K, Seppanen M, et al. Noninvasive diagnosis of focal hyperinsulinism of infancy with [18-F]-DOPA positron emission tomography. Diabetes 2006;55:13-8. 10. Mohnike K, Blankenstein O, Minn H, et al. [18F]-DOPA positron emission tomography for preoperative localization in congenital hyperinsulinism. Horm Res 2008;70:65-72. 11. Carcassonne M, DeLarue A, LeTourneau JN. Surgical treatment of organic pancreatic hypoglycaemia in the pediatric age. J Pediatr Surg 1983;18:75-9. 12. Langer JC, Filler RM, Wesson DE, et al. Surgical management of persistent neonatal hypoglycaemia due to islet cell dysplasia. J Pediatr Surg 1984;19:786-92. 13. Thomas CG, Jr, Cuenca RE, Azizkhan RG, et al. Changing concepts of islet cell dysplasia in neonatal and infantile hyperinsulinism. World J Surg 1988;12:598-609. 14. Lovvorn HN III, Nance ML, Ferry RJ, Jr, et al. Congenital hyperinsulinism and the surgeon: lessons learned over 35 years. J Pediatr Surg 1999;34:786-93. 15. Spitz L. Surgery for hyperinsulinemic hypoglycaemia. In: Spitz L, Coran AG, eds Operative Pediatric Surgery, 6th edn London: Hodder Arnold, 2006:733-8. 16. Nihoul-Fekete C, de Lonlay P, Jaubert F, et al. The surgical management of congenital hyperinsulinemic hypoglycaemia in infancy. J Pediatr Surg 2004;39:267-9. 17. Shilyansky J, Fisher S, Cutz E, et al. Is 95% pancreatectomy the procedure of choice for treatment of persistent hyperinsulinemic hypoglycemia of the neonate? J Pediatr Surg 1997;32:342-6. 18. Al-Nassar S, Sakati N, Al-Ashwal A, et al. Persistent hyperinsulinaemic hypoglycaemia of infancy in 43 children: long-term clinical and surgical follow up. Asian J Surg 2006;29:207-11. 19. De Lonlay-Debeney P, Poggi-Travert F, Fournet J-C, et al. Clinical features of 52 neonates with hyperinsulinism. N Engl J Med 1999; 340:1169-75. 20. McAndrew HF, Smith V, Spitz L. Surgical complications of pancreatectomy for persistent hyperinsulinaemic hypoglycaemia of infancy. J Pediatr Surg 2003;38:13-6. 21. Al-Shanafey S, Habib Z, AlNassar S. Laparoscopic pancreatectomy for persistent hyperinsulinemic hypoglycemia of infancy. J Pediatr Surg 2009;44:134-8. 22. Spitz L, Bhargava RK, Grant DB, et al. Surgical treatment of hyperinsulinaemic hypoglycaemia in infancy and childhood. Arch Dis Child 1992;67:201-5. 23. Bax KN, Van der Zee DC. The laparoscopic approach toward hyperinsulinism in children. Semin Pediatr Surg 2007;16:245-51.
Surgical management of congenital hyperinsulinism of infancy Agostino Pierro, MD, PhD, Shireen A. Nah, MRCS, MS From the Department of Paediatric Surgery, UCL Institute of Child Health and Great Ormond Street Hospital for Children, London, United Kingdom. KEYWORDS Hyperinsulinemia; Hypoglycemia; Pancreas; Laparoscopic; Child; Infant
Congenital hyperinsulinism of infancy (CHI) is characterized by inappropriate insulin secretion resulting in persistent hypoglycemia, which can lead to irreversible severe neurological damage in the infant. Many patients with CHI will respond to medical therapy, but surgery is necessary in those that do not. There are 2 main histologic subtypes, diffuse and focal, both of which may require different surgical strategies. Near-total pancreatectomy is the procedure of choice for diffuse CHI, whereas a localized resection is curative in focal CHI. Open surgery is the traditional approach to pancreatic resection. However, laparoscopy is increasingly used, particularly in localized resection for focal disease. We describe both methods of pancreatectomy. © 2011 Elsevier Inc. All rights reserved.
Congenital hyperinsulinism of infancy (CHI) is characterized by inappropriate insulin secretion resulting in persistent hypoglycemia, which can lead to irreversible severe neurological damage in the infant.1 The diagnosis of CHI is based on the following parameters: glucose infusion rate ⬎8 mg/kg/min, laboratory blood glucose ⬍3 mmol/L, detectable insulin/C-peptide, hypoketosis, undetectable/low free fatty acids, and a positive glycemic response to glucagon. Medical therapy is instituted in children with confirmed CHI that consists of a combination of diazoxide (⫾chlorothiazide), nifedipine, and glucagon/octreotide.2,3 Serum biochemical analysis is performed to identify some of the rarer causes of CHI (eg, hyperammonemia). Medically unresponsive children who continue to require intravenous glucose infusion despite maximal medical therapy are treated by pancreatic resection, the extent of which is determined by the histologic type.
Address reprint requests and correspondence: Agostino Pierro, MD, PhD, Department of Paediatric Surgery, Institute of Child Health, 30 Guilford Street, London WC1N 1EH. E-mail address: [email protected]; [email protected].
1055-8586/$ -see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1053/j.sempedsurg.2010.10.009
There are 2 main histologic subtypes: diffuse (60%-70% of patients) and focal (30%-40% of patients).4 To distinguish between diffuse and focal subtypes, a genetic analysis is performed.5 Typically children with diffuse CHI have homozygous recessive or compound heterozygote mutations in the ABCC8 and KCNJ11 genes (which encode the SUR1 and KIR6.2 proteins of the pancreatic beta-cell).5 Focal CHI is associated with loss of heterozygosity for paternally inherited mutations in the Katp genes.6 Children without characteristic genetic mutations of diffuse CHI undergo a 18F-L-3,4-dihydroxyphenylalanine positron emission tomography combined with computed tomography scan (18F-DOPA-PET-CT scan). The PET-CT scan distinguishes between diffuse and focal disease, where diffuse CHI exhibits a diffuse uptake on the PET-CT scan. In focal disease, the scan assists in localizing the site of the focal lesion, allowing a more directed pancreatic resection (Figure 1).7-10 Histologic examination is carried out both intraoperatively and postoperatively. Intraoperative specimens are collected and sent for frozen section analysis. In diffuse CHI, the tail of the pancreas is resected and sent for urgent frozen section histologic analysis to confirm the diagnosis
Pierro and Nah
Surgical Management of CIH of Infancy
51
Open near-total pancreatectomy
Figure 1 18F-DOPA-PET-CT scan, axial view. Greater standardized uptake value indicates a focal lesion. (A) Focal uptake is seen in the head of the pancreas, indicating the presence of a focal lesion. (B) Focal uptake is seen in the tail of the pancreas, indicating the presence of a focal lesion. (Used with permission from the Journal of Pediatric Surgery.) (Color version of figure is available online.)
of diffuse CHI. Further resection only commences when this confirmation has arrived. In focal CHI, the lesion is removed with surrounding normal pancreatic tissue. Intraoperative confirmation of clear resection is essential before the patient is extubated.
The abdomen is accessed via a generous transverse supraumbilical incision. The lesser sac is entered through the gastrocolic omentum; kocherization of the duodenum allows full exposure of the pancreas. The tail of the pancreas is sent for intraoperative frozen section histology and the diagnosis of diffuse CHI is confirmed before proceeding with pancreatectomy. A stay suture is placed in the tail of the pancreas to allow traction of the pancreas facilitating its dissection because direct handling of the pancreas results in fracture of this friable organ. The tail of the pancreas is carefully dissected away from the hilum of the spleen, and the short pancreatic vessels are coagulated. Dissection of the pancreas is carried out in a medial direction towards the head of the pancreas. Pancreatic vessels passing from the splenic vessels into the pancreas are coagulated and divided using bipolar diathermy. Meticulous care is taken with the splenic artery and vein which are closely related to the pancreas, as the spleen should be preserved. Once dissection has arrived at the superior mesenteric vessels, the uncinate process is mobilized. A sling may be placed around the superior mesenteric vessels, retracting them away from the uncinate process. As the head of pancreas is approached, attention is directed to identifying the course of the common bile duct. A sling is placed around the bile duct superior to the first part of the duodenum. A blunt forceps is then passed from within the C-loop of the duodenum behind the first part of the duodenum to grasp the sling, bringing it out superior to the head of pancreas. This becomes the guide to the position of the common bile duct during subsequent dissection of the pancreas. The head of the pancreas is mobilized, and the superior and inferior pancreaticoduodenal vessels are divided. The pancreatic duct is ligated with nonabsorbable sutures and divided. A rim of pancreatic tissue surrounding the common bile duct and along the duodenum is left remaining after near-total pancreatectomy (Figure 2). The abdomen is closed in layers using absorbable sutures. Postoperatively, the patient has both nasogastric tube and bladder catheter. Enteral feeds are restarted after the gastrointestinal function has returned.
Diffuse CHI Most published series agree that that a “near-total” pancreatectomy is required to prevent an unacceptably high incidence of recurrent hyperinsulinemia, with some suggesting that up to a 98% pancreatectomy may be required in refractory cases.11-14 In near-total pancreatectomy, the tail, body, uncinate process and part of pancreatic head are resected, leaving a rim of pancreatic tissue surrounding the common bile duct and along the duodenum (Figure 2). In a 98% pancreatectomy, only small islands of tissue are left along the pancreaticoduodenal arcade bordering the duodenum.15
Figure 2 Near-total pancreatectomy. The shaded area indicates the resected pancreas, leaving behind an amount pancreatic tissue around the common bile duct and along the medial border of the duodenum.
52
Seminars in Pediatric Surgery, Vol 20, No 1, February 2011
Laparoscopic near-total pancreatectomy An umbilical 10-mm Hasson port is inserted by an open technique and a 5-mm 30° camera is introduced. Three additional ports are placed: a 5-mm port in the left lower quadrant, a Nathanson retractor at the epigastrium, and a further working port (3 or 5 mm) in the right flank. The gastrocolic omentum is divided and the lesser sac is entered. The Nathanson retractor is used to retract the stomach. The head of the patient is elevated. A stay suture is inserted into the tail of the pancreas which is used to retract the pancreas superiorly. Dissection of the pancreas proceeds towards the head. The short pancreatic vessels passing from the splenic vessels into the pancreas are divided using a 3-mm hook diathermy at very high coagulation settings. These vessels are the most common source of intraoperative hemorrhage, which may be controlled by applying gentle pressure using an atraumatic bowel grasper. The pancreatic tail is transected using the Harmonic Scalpel (Ethicon Endosurgery). The pancreatic tail is removed via the umbilical 10 mm port and sent for frozen section analysis to confirm the diagnosis of diffuse CHI. No further resection takes place until this confirmation has been obtained. Subsequent dissection is facilitated by the insertion of a stay suture at the cut surface of the remaining pancreas which is resected in segments of approximately 2 cm. As dissection nears the head of the pancreas, stay sutures are placed in the uncinate process and the head of pancreas which are retracted superiorly. A neartotal pancreatectomy is achieved by leaving an adequate amount of pancreatic tissue along the medial border of the duodenum where the common bile duct is expected (Figure 2). Port sites are closed using absorbable sutures. No drains are used.
Focal CHI In patients with focal CHI, a localized resection of the focal lesion is curative.3,16 Before surgery, the diagnosis of focal CHI is confirmed by the use of a combination of genetic analysis and findings on 18F-DOPA-PET-CT scan. The site of the lesion seen on PET-CT scan allows preoperative planning of the anticipated procedure. However, it should be noted that the accuracy of localization in PET-CT Scan is approximately 70%.7 In proximal lesions in the head and neck of the pancreas, open resection of the lesion with a small rim of surrounding normal pancreatic tissue is carried out and pancreaticojejunostomy is performed to allow drainage of the distal pancreas. In distal lesions, a distal pancreatectomy may be done laparoscopically (Figure 3).
Figure 3 Focal CHI. (A) Lesion in the head or neck of pancreas (zone A: unshaded area). Surgery: Open excision of focal lesion and pancreaticojejunostomy. (B) Lesion in the body or tail of pancreas (zone B: shaded area). Surgery: Laparoscopic or open distal pancreatectomy.
focal CHI, the lesion is often deep within the parenchyma of the pancreas and may not be visually evident. An intraoperative biopsy is performed for frozen section histologic examination. Histology may reveal the following: (1) the presence of the focal lesion completely resected (normal pancreas at the resection margin); (2) focal lesion not completely resected; (3) the presence of normal pancreas excluding the presence of diffuse CHI and indicating that the focal lesion has not yet been excised.
Focal lesion in head or neck of pancreas When the focal lesion is deep in the head or neck of the pancreas, the procedure may be converted to open and dissection of the head of the pancreas is commenced (Figure 3A). Superficial lesions may be enucleated laparoscopically. A sling may be passed behind the neck of the pancreas to facilitate traction of the pancreas away from the pancreatic bed. Short pancreatic vessels are meticulously ligated using bipolar diathermy and divided. The head of the pancreas is dissected in the direction of the duodenum, carefully avoiding the common bile duct. A pancreaticojejunostomy is then constructed to allow drainage of the distal pancreas.
Focal lesion in body or tail of pancreas In more distal lesions, the entire procedure may be completed either laparoscopically or open (Figure 3B). Once histologic confirmation of focal disease is obtained, the pancreas is dissected as described previously. Dissection is performed until the resected specimen includes the lesion. The pancreas is transacted with the Harmonic Scalpel (Ethicon Endosurgery, Cincinnati, OH). An adequate resection margin is confirmed by further frozen section analysis. There is no need for drains.
Surgery for focal CHI The abdomen is accessed laparoscopically as described previously. The pancreas is inspected and palpated for a nodular area, which indicates the site of the focal lesion. In
Postoperative management Enteral feeds are recommenced as early as the first postoperative day and gradually advanced, reducing the intrave-
Pierro and Nah
Surgical Management of CIH of Infancy
nous infusion of dextrose. It is not unusual to observe a period of gastroparesis, particularly after excision of the head of the pancreas for focal lesions or near-total pancreatectomy for diffuse CHI. This may last 2-3 days. The management of postoperative hypoglycemia may require medical treatment. However, this is usually transient. Further resection of the pancreas is needed when bolus enteral feeding and cessation of continuous intravenous glucose is not achieved.
Complications Several reports have been published on the outcomes and complications of open pancreatectomy.14,17-22 The most serious complications are associated with near-total pancreatectomy and include recurrent hyperinsulinemic hypoglycemia which may require repeat pancreatic resection, biliary tree injury, and pancreatic endocrine and exocrine insufficiency. McAndrew et al20 reported on 48 patients undergoing open near-total pancreatectomy for CHI. There was 1 splenic injury, 1 small bowel injury, and 1 adhesive obstruction. There were 7 patients (15%) who had bile duct injury. Treatment for persistent hyperinsulinism was required in 11 (23%) patients, 9 of whom required further pancreatic resection. Diabetes mellitus was observed in 20 (42%) patients and exocrine deficiency requiring enzyme therapy was present in 13 (27%) patients. In other published series of open pancreatectomy, complications were seen in 8%-21% of patients.14,17-21 Biliary tree injury was reported in all open series with an incidence of 2%-15%. The incidence of further pancreatic resection for persistent CHI ranged from 8% to 33%; the need for medical treatment for persistent hypoglycemia ranged from 0% to 58%. Postoperative diabetes mellitus was seen in 12%-56% of patients, and the need for pancreatic enzyme replacement was 4%-37%. There are few published reports on laparoscopic pancreatectomy for CHI.21,23 Al-Shanafey et al21 reported 12 children who had laparoscopic near-total pancreatectomy. Eight (67%) patients had persistent hypoglycemia, one required further resection and there were no bile duct injuries.
Conclusions The management of CHI is challenging and requires a multidisciplinary approach. Pancreatectomy is necessary when medical therapy fails. Successful surgery is dependent on good preoperative assessment using genetic analysis and PET-CT scan, reliable intraoperative histologic analysis and meticulous surgical technique. The extent of surgery and type of procedure are determined by histology and site of the lesion; this may be a partial pancreatectomy for focal lesions or near-total pancreatectomy for diffuse congenital hyperinsulinism.
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