Insulinoma is a rare pancreatic endocrine tumor, typically sporadic and solitary. Over 90% of all insulinomas are benign. The Whipple triad of low blood glucose levels (below 50 mg/dL), hypoglycemia symptoms especially after fasting or heavy exercise, and dramatic reversal of central nervous system abnormalities by glucose administration is often present.5
Although patients with insulinoma have symptoms of hypoglycemia resulting from neuroglycopenia and increased catecholamine release, the diagnosis can be difficult in cases with incomplete functional activity. Blunted symptoms of hypoglycemia and negative laboratory investigations can retard the diagnosis,6 and symptoms may be misattributed to psychiatric, cardiac, or neurological disorders.7 In our case, the diagnosis was preceded in the previous year by several episodes of weakness, sweating, and pallor, which abated spontaneously or after having a snack. The above symptoms had been underestimated by the patient, and no diagnostic procedure had been undertaken before the major episode of loss of consciousness. The present case underlines that, even in the presence of relatively vague complaints, an early diagnosis is essential to prevent major hypoglycemic episodes which can be potentially lethal both directly and by causing injury, as in motor vehicle accidents caused by loss of consciousness. In this setting, a proper and orderly diagnostic approach is essential to rule out the presence of an insulin-secreting tumor.
The appropriate diagnostic steps for a biochemical diagnosis of insulinoma include determination of circulating levels of insulin and C-peptide, and plasma insulin/glucose ratio. A suppression test is also usually needed. Although endogenous insulin production is normally suppressed in the setting of hypoglycemia, the lack of suppression during a 72-hour fast is a strong indicator of the presence of an insulin-secreting tumor. During the test, usually supervised in a hospital setting, capillary blood glucose is measured using a reflectance meter every 4 hours (and every hour when blood glucose is <60 mg/dL). When values are <50 mg/dL, or the patient has symptoms of hypoglycemia, a blood test is drawn for serum glucose, insulin, proinsulin, and C-peptide levels, and the fast is stopped.
Once a biochemical diagnosis of insulinoma is established, localization of the tumor is usually obtained with noninvasive imaging modalities.8 Although scintigraphy with 111In-octreotide is widely used for diagnosing somatostatin receptor positive tumors, it has a low sensitivity in detecting insulinomas, probably due to the lack of somatostatin receptors type 2 and the small size of the lesions.8 Whereas the sensitivity of transabdominal ultrasonography in the localization of insulinomas is poor (ranging from 9% to 64%), contrast-enhanced abdominal CT is currently accepted as the first-line investigation for the visualization of insulinomas. Insulinomas are typically hypervascular and, thus, demonstrate a greater enhancement than normal pancreatic parenchyma during the arterial and capillary phases of contrast bolus. The use of multidetector CT may increase the sensitivity of the technique.9 Magnetic resonance imaging is a suitable alternative to CT, has a similar or better sensitivity and specificity, and is probably the investigation of choice in defining hepatic metastases.10
In the case of small insulinomas not detected with the above noninvasive imaging modalities, invasive procedures may still be necessary to achieve preoperative localization. Endoscopic ultrasonography has a reported sensitivity of 87% to 92%, although it is largely operator dependent and its sensitivity is lower for insulinomas in the tail of the pancreas or extrapancreatic.11 Angiography combined with arterial stimulation venous sampling, using calcium as the insulin secretagogue, is probably the most sensitive available diagnostic technique, with an accuracy ranging from 94% to 100%.12 Manual palpation of the pancreas by an experienced surgeon and ultrasonography are both sensitive methods for the intraoperative detection of the site of insulinomas.
Surgical excision is the treatment of choice and is curative in most cases.13 After surgical therapy, patients with insulinomas generally have excellent long-term survival. Medical therapy with diazoxide, calcium channel blockers, Dilantin, and somatostatin is reserved for the cases which cannot undergo surgery.
Minimally invasive surgery for pancreatic diseases is a major new research field in abdominal surgery, which has been developed in the past 2 decades. The traditional laparoscopic approach is now widely used in the execution of a distal pancreatectomy for benign diseases, although there is still a lack of solid evidence.14 More controversial is the application of this approach in malignancies, in which the surgeon must ensure the same radical approach as the open technique. In the early 2000s, minimally invasive surgery underwent a great revolution with the introduction of robotic systems to overcome the limitations of traditional laparoscopy. The first case of robot-assisted distal pancreatectomy was described by Melvin et al in 2003.15
Technical limitations of laparoscopic pancreatic surgery include a restricted range of motion and the 2-dimensional operative field. Articulation of robotic instruments, physiological tremor suppression, 3D vision, and a stable image allow the surgeon to perform complex resection and anastomosis with the same techniques of the traditional open surgery.16 Another source of concern is represented by the costs of the procedure, although the increased accuracy and safety in tissue dissection may reduce postoperative complications and hospital stay, so decreasing overall costs.17
A recent systematic review of 5 nonrandomized studies on the topic18 showed some interesting aspects requiring further investigation. First, the procedure has a high feasibility, with a reported rate of conversion to open surgery of less than 5%. Major complications (Clavien grade III or IV) were only 0% to 5% among studies, with a pancreatic fistula rate of 15.4%. Overall, the review18 reported a 30-day postoperative morbidity between 0% and 18% and a 90-day postoperative mortality of 0% in all included studies. Perhaps, one of the most interesting aspects is the ability to perform a distal pancreatectomy with spleen preservation. In this respect, robotic surgery has a higher success rate than laparoscopy.19 A study by Kim et al20 confirms a considerably higher spleen-preserving rate in the robotic than in the laparoscopic group (P = 0.027).
However, we must emphasize that many different techniques have been reported in the literature, and standardization of the procedures is under way.21
The case above highlights the complexity of the diagnosis of insulinoma when symptoms are nonspecific. It also underlines the importance of appropriately investigating for insulinoma hypoglycemic patients suffering or causing road traffic accidents. Robot-assisted distal pancreatectomy is a new treatment and there is still not enough data to draw final conclusions compared with conventional or laparoscopic surgery. In this case, the robotic approach allowed to achieve excellent results in terms of oncological outcomes, reduced postoperative pain, shorter hospital staying, early resumption of intestinal motility, and early oral nutrition, although the expected duration of the surgical intervention is usually longer than with laparoscopic or open surgery.
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20. Kim DH, Kang CM, Lee WJ, et al. The first experience of robot assisted spleen-preserving laparoscopic distal pancreatectomy in Korea. Yonsei Med J
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21. Parisi A, Coratti F, Cirocchi R, et al. Robotic distal pancreatectomy with or without preservation of spleen: a technical note. World J Surg Oncol