Laparoscopic Near-Total Pancreatectomy for Persistent Hyperinsulinemic Hypoglycemia of Infancy: Report of Two Cases

Abstract

Near-total pancreatectomy for persistent hyperinsulinemic hypoglycemia (PHH) of infancy has been done, so far, only by open surgery, and the application of laparoscopic techniques for this procedure has not been documented. In this article, we report 2 cases of successful laparoscopic near-total pancreatectomy for PHH. Two infants underwent surgery at the age of 60 and 54 days and at body weights of 7700 and 5700 g, respectively. Four ports were used for the patient 1 and three ports plus fixation sutures of the stomach to the abdominal wall for stomach traction were used for patient 2. The pancreas was dissected free from the spleen and splenic vessels and was mobilized beyond the right side of the superior mesenteric vein. The head of the pancreas was transected by using the Harmonic Scalpel (Tokyo, Japan), leaving only 1 cm of the pancreas along the duodenal C-loop. The operative times were 180 and 160 minutes. There was neither an intra- nor a postoperative abdominal complication. Oral feeding was resumed on the postoperative day 1. The blood glucose level increased immediately after the operation. Follow-up period of 12 months showed normal levels of blood sugar and insulin for both patients. Laparoscopic near-total pancreatectomy can be a safe, effective procedure for small infants with PHH.

Introduction

Persistent hyperinsulinemic hypoglycemia (PHH) is the most common cause of persistent hypoglycemia in neonates and infants.^1,2 Untreated PHH can cause permanent neurologic damage or even death.^3–5 Two types of histopathologic lesions of the pancreas are described in PHH: focal and, more commonly, diffuse.^1,2 Treatment usually begins with a glucose-enriched diet and medical inhibition of insulin secretion. Unfortunately, many cases of PHH are unresponsive to medical therapy, and surgical pancreatectomy is required in such circumstances.^1–10 While for the focal type of PHH enucleation or limited pancreatic resection is curative, near total pancreatectomy (NTP) is necessary for the diffuse type.^5–9 Although laparoscopic limited pancreatic resection was reported to be feasible for focal PHH in several studies,^11,12 no experience with laparoscopic NTP for diffuse PHH has been documented. In this article, we report our first 2 cases of NTP for PHH, which were operated on successfully by laparoscopic approach.

Case Reports

Case 1

A girl of unrelated healthy parents was born with a birth weight of 4200 g after an uneventful pregnancy and normal delivery. During the first days after birth, she had episodes of arm tremors, ocular clonus, and was admitted to a local hospital. Persistent hypoglycemia was discovered and treated unsuccessfully, and the child was referred to the National Hospital of Pediatrics (NHP; Hanoi, Vietnam). Her blood-sugar level ranged from 0.8 to 2.8 mmol/L, and the level of blood insulin was 66 μIU/mL. An abdominal ultrasound showed a normal pancreas and other parenchymal organs. The diagnosis of PHH was established and treatment was initiated, consisting of administration of glucose orally and intravenously (8–10 mg/kg/min) and diazoxide (10 mg/kg/day). However, blood-sugar levels remained low and symptoms persisted. After unsuccessful medical treatment, the patient was operated on at the age of 60 days and with a body weight of 7700 g. Three ports were initially placed: a 10-mm port at 3 cm below the navel and two 5-mm ports in the right- and left-upper quadrants. After opening the greater omental sac, the pancreas was exposed and carefully explored, with no abnormality found. The pancreatic tail was dissected free from the splenic hilum, splenic artery, and vein. The body of the pancreas was mobilized; the pancreatic neck was detached from the superior mesenteric vein (SMV) and the portal vein (PV). NTP was carried out by a Harmonic Scalpel, leaving only 1 cm of pancreatic tissue along the duodenum. For this stage, a fourth trocar, placed superiorly and medially to the port on the right side, was needed to retract the duodenum and protect it from the scalpel tip. The pancreatic stump was sutured with 5/0 PDS (Johnson & Johnson Int'l, St.-Stevens-Wolowe, Belgium). The operative time was 180 minutes. The blood loss was minimal. The blood-sugar level increased immediately after the operation and the child started feeding the next day. Intravenous glucose administration was stopped on day 3 postoperatively. The blood-sugar level remained in the normal range and the child was discharged with normal feeding. In follow-up at 12 months postoperatively, the child is healthy with normal levels of blood sugar and insulin.

Case 2

After an uneventful pregnancy, a 4900-g boy was born to unrelated healthy parents by caesarean section because of his large size. Six days after birth, he was lethargic and cyanotic with hypersalivation, poor sucking, ocular clonus, and hyporeflexia. After admission to NHP, an investigation showed persistent hypoglycemia (0.8–2.2 mmol/L) associated with hyperinsulinemia (76 mIU/L). Pancreatic ultrasound was normal. The diagnosis of PHH was established and the child was treated with frequent glucose feedings, intravenous glucose infusion (8–10 mg/kg/min), and diazoxide 10 mg/kg. After unsuccessful medical treatment, the patient was operated at the age of 54 days and with a body weight of 5700 g. Three ports were placed: the 10-mm trocar in the umbilicus and two 5-mm trocars in the right- and left-upper quadrants. Intraoperatively, the pancreas was macroscopically normal and no focal abnormality was detected. A stay suture (through the abdominal wall) was used to elevate the stomach superiorly. Although part of the splenic vasculature was buried in the pancreatic tail parenchyma, the vessels were successfully detached from the pancreas. The body of the pancreas was detached from the SMV and then transected. The distal pancreas was progressively dissected and freed from the splenic vessels. After exposure and mobilization of the medial part of the pancreatic head, the pancreas was resected nearly totally, as described above. The operative time was 160 minutes. Blood loss was not significant. Postoperatively, the child started feeding on the first day (POD1) and the blood-sugar level was normal for 4 days (until POD4). Hyperglycemia ensued, however (serum glucose ranging from 11.3 to 28.7 mmol/L), and insulin (0.5 U/kg/day) was needed to restore normoglycemia. The child was discharged in stable condition with normal feeding and insulin prescription. Two weeks later, the child became normoglycemic without insulin therapy and follow-up 12 months postoperatively showed no clinical symptoms, normal blood sugar, and insulin levels. Pathologic study on the resected pancreatic tissue from both patients found no focal lesions.

Discussion

Surgery is required for cases of PHH, which are resistant to medical management. However, the extent of pancreatectomy depends on PHH type. In comparison to enucleation or limited pancreatic resection as surgical procedures for focal type PHH, NTP for diffuse PHH is technically more demanding and is associated with higher morbidity and significant risk of development of diabetes mellitus.^9,10 Classically, NTP is an open surgical procedure consisting of dissection of the pancreas off the major vascular structures (i.e., splenic artery and vein, inferior and superior mesenteric veins, and portal vein) and resection of 95–98% of the pancreas, leaving only a part of the head of the pancreas along the duodenum C-loop. Complications of NTP, such as splenic injury, duodenal fistula, pancreatic and bile leak, sepsis, and even death, have been reported.^9,10 Therefore, preoperative differentiation between the two types of PHH is of utmost importance. Diagnostic studies, such as acute insulin response to calcium and tolbutamide stimulation, pancreatic venous sampling, and selective pancreatic arterial calcium stimulation with hepatic venous insulin sampling, have been tried, with mixed results.¹ Positron emission tomography, using ¹⁸F-L-dopa for imaging, has recently emerged as a new and promising method.¹³ In both cases reported above, laparoscopic exploration was used as a method for excluding focal lesions. This technique plus laparoscopic ultrasound have also been used by other researchers with good results.^11,14

Laparoscopy as a tool for diagnosis and treatment of various pancreatic diseases, including insulinoma, has been well documented in adults.^15–19 Its application in children, especially in small infants with PHH, is still limited. Several cases of focal-type PHH,^11,12 and only 1 case of a 4-week-old infant with diffuse PHH treated by laparoscopic distal pancreatectomy, have been reported.²⁰ Because of persistent postoperative hypoglycemia, that child subsequently underwent open NTP.

In both our cases, NTP was performed successfully by the laparoscopic approach. We used a 10-mm port for laparoscope insertion and for removal of the resected pancreas. Depending on the patient's age, this 10-mm port was placed below the umbilicus or through it. Four instrumental ports have been used in other centers for laparoscopic pancreatic resection.¹⁸ In our experience, two to three instrumental ports are sufficient, since a fixation suture to the abdominal wall can be used for stomach traction, as needed. Some researchers have reported difficulty in preserving the spleen at distal pancreatectomy.^12,16 In our view, meticulous dissection, using a fine-tipped instrument to coagulate small vessels between the splenic vessels and the pancreas, is useful to avoid unnecessary splenectomy. To achieve NTP, it is necessary to dissect the pancreas from the SMV, PV, and further on the right side. Both our patients recovered without any local abdominal complication. Minimal abdominal wall trauma, excellent cosmetic result, and early resumption of oral feeding and bowel movements are all advantages of laparoscopic NTP techniques.

Until now, for diffuse PHH, the exact volume of pancreas to be removed is not identified. The risk of diabetes mellitus after NTP is still significant and unpredictable, as documented in numerous studies.^9–11 Long-term follow-up data have showed that certain patients have developed diabetes mellitus even years after near total and subtotal pancreatectomy.⁹ While our first patient recovered serum glucose regulation well, the second one required insulin therapy for a short time after the same volume of pancreatectomy.

Conclusion

To our knowledge, this is the first report on successful laparoscopic NTP for PHH. The reported cases have shown that laparoscopic near-total pancreatectomy can be a safe, effective procedure for small infants with PHH.

Footnotes

Disclosure Statement

No competing financial interests exist.

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