Seeking the unseen: Localization and surgery for an occult sporadic insulinoma

Ann Hepatobiliary Pancreat Surg 2020;24:234-238 https://doi.org/10.14701/ahbps.2020.24.2.234 Case Report Seeking the unseen: Localization and surgery for an occult sporadic insulinoma Duminda Subasinghe1,2, Sonali Sihindi Chapa Gunatilake3, Vihara Erangika Dassanyake1,2, Chaminda Garusinghe3, Eranga Ganewaththa4, Chinthaka Appuhamy4, Noel P. Somasundaram3, and Sivasuriya Sivaganesh1,2 1 Division of HPB Surgery, Department of Surgery, Faculty of Medicine, University of Colombo, The University Surgical Unit, The National Hospital of Sri Lanka, Departments of 3Endocrinology and Diabetes and 4 Interventional Radiology, The National Hospital of Sri Lanka, Colombo, Sri Lanka 2 Insulinomas are rare pancreatic neuroendocrine tumours and the commonest cause for endogenous hyperinsulinaemic hypoglycemia. Small tumours are not easily detected by conventional cross-sectional imaging making localization prior to surgical removal a challenge. Selective arterial calcium stimulation is an invaluable adjunct to localization in such circumstances. This is further supplemented by intraoperative ultrasonography. A 39-year-old male was referred with features of Whipple’s triad of 10 months duration. Clinical and biochemical evaluation including C-peptide and serum insulin levels during supervised hypoglycemia concluded endogenous hyperinsulinaemia as the underlying aetiology. Contrast CT and MRI of the abdomen failed to localize the tumour. Selective arterial calcium stimulation localized the lesion in distal pancreas. During the surgery, tumour was further localized to the tail of the pancreas using intraoperative ultrasonography and enucleated. Histology confirmed an insulinoma and patient made an unremarkable recovery and was well more than a year after the surgery. (Ann Hepatobiliary Pancreat Surg 2020;24:234-238) Key Words: Insulinoma; Selective arterial calcium stimulation; Enucleation INTRODUCTION ful localization was achieved with selective arterial calcium stimulation (SACS) with hepatic venous sampling Insulinomas are rare but the commonest among pancre1 and intra-operative ultrasonography (IOUS) after cross sec- atic neuroendocrine tumours (pNET). Most are intrapan- tional imaging failed to localize the lesion. To our knowl- creatic, benign and solitary and have an excellent prog- edge, this is the first such report from Sri Lanka and high- nosis after surgical removal. The majority are ＜2 cm in lights the benefits of harnessing multidisciplinary expert- size and distributed equally in the head, body and tail of ise to achieve optimal outcomes in challenging cases. 2 the pancreas. Thus, preoperative localization is key to planning surgery. This will prevent prolonged intraopera- CASE tive attempts to locate and at worst failure to remove the lesion despite laparotomy. Techniques used in preoper- A 39-year-old male was evaluated for clinical features ative localization include transabdominal ultrasonography, of hypoglycaemia of 10 months. These episodes corre- contrast enhanced computed tomography (CECT), magnetic sponded with low capillary blood glucose (CBG) assays resonance imaging (MRI), endoscopic ultrasonography of up to 46 mg/dl and fulfilled Whipple’s triad. He had (EUS) and selective arterial calcium stimulation with hep- an otherwise normal premorbid status and clinical exami- 2 atic venous sampling. We present a patient with endoge- nation was unremarkable. A supervised 72-hour fast com- nous hyperinsulinaemic hypoglycaemia in whom success- bined with CBG (31mg/dl) serum insulin (71.28 pmol/L Received: October 23, 2019; Revised: February 17, 2020; Accepted: March 4, 2020 Corresponding author: Duminda Subasinghe Division of HPB Surgery, Department of Surgery, Faculty of Medicine, University of Colombo, No. 25, P.O. Box 271, Kynsey Road, Colombo 00800, Sri Lanka Tel: +94-716-862-656, Fax: +94-112-671-846, E-mail: dumindas1982@yahoo.com Copyright Ⓒ 2020 by The Korean Association of Hepato-Biliary-Pancreatic Surgery This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Annals of Hepato-Biliary-Pancreatic Surgery ∙ pISSN: 2508-5778ㆍeISSN: 2508-5859 Duminda Subasinghe, et al. Occult sporadic insulinoma 235 [normal ＜21 pmol/L]) and C-peptide level (2.57 nmol/L insulin levels above the baseline was observed in the [normal ＜0.2 nmol/L]) and negative sulfonylurea test proximal and distal splenic artery branches, localizing the confirmed endogenous insulin dependent hypoglycaemia. tumour to the distal body or tail of the pancreas (Fig. 3, Multiple endocrine neoplasia I (MEN I) syndrome screen- Table 1). ing was negative. Surgery was performed through a bilateral subcostal Contrast enhanced CT abdomen in the early arterial incision. The pancreatic body and tail were mobilized with phase and MRI with gadolinium contrast failed to demon- the spleen but the tumour could not be located by palpa- strate a pancreatic lesion (Fig. 1). SACS was performed tion. Intraoperative ultrasonography (IOUS) located a 1.0× 3 as per standard protocol. In brief, selective cannulation 0.8 cm tumour in the pancreatic tail adjacent to the splen- and calcium injection into arteries supplying segments of ic hilum and this was enucleated (Fig. 4). IOUS also ex- the pancreas was performed. Insulin assays were performed cluded the presence of multiple tumours (Fig. 5). Histol- on pre and post calcium infusion catheter samples ob- ogy confirmed a WHO grade 1 tumour (Ki67 - 1.8%) pNET tained from the hepatic veins (Fig. 2). A two-fold rise in or insulinoma (positive staining for NSE). The patient made an uneventful recovery and was normoglycaemic at follow up more than a year later. DISCUSSION Most sporadic insulinomas are solitary and under 2 cm; hence parenchymal sparing complete enucleation is the procedure of choice to minimise morbidity while preventing recurrence. Tumour localization facilitates this and changes in surgical approach if necessary and is an integral part of workup. This case highlights the challenges of pre and intraoperative localization of insulinomas and tools to overcome them. Cross sectional imaging failed to localise the tumour in this patient. This is not surprising considering that the senFig. 1. CECT abdomen showing normal pancreas. Fig. 2. Selective arterial calcium stimulation; (A) Catheter in hepatic vein, (B) Superior mesenteric artery, (C) Splenic artery. Fig. 3. Insulin levels of arterial territories at selective arterial calcium stimulation test. 236 Ann Hepatobiliary Pancreat Surg Vol. 24, No. 2, May 2020 www.ahbps.org Table 1. Results of selective arterial calcium stimulation test Insulin levels (pmol/L) Time after calcium injection 0 30 60 90 120 sec sec sec sec sec Superior mesenteric artery Gastro-duodenal artery Hepatic artery 343.0 308.5 206.7 319.3 362.28 234.43 216.06 205.37 197.92 223.47 215.16 222.0 194.19 213.15 22.02 Prox. splenic artery Distal splenic artery 211.75 237.02 2631.18 2909.75 993.80 372.22 1126.22 2112.81 1164.90 462.57 Fig. 4. Insulinoma visualized with intraoperative US combined with Doppler. EUS has proven to be a an effective modality in these situations with an overall sensitivity of 80-90% though 6,7 this drops sharply for tumours in the tail (37-50%). The lack of available expertise at the time precluded its use in this patient. SACS is an interventional radiological technique used to preoperatively localize or regionalize occult insulinomas with excellent sensitivity (84-100%) and specificity (94100%). 8-11 Only 20% of patients who undergo surgical management for insulinoma require preoperative SACS, 12 as the majority are localized with non-invasive imaging. SACS was developed by Doppman et al. 8,13,14 in 1989 as a way to localize discrete insulin-secreting islet cell tumours of the pancreas. It is used on the basis that insulinomas have a dominant arterial supply and calcium elicits a unique 14 response on tumour cells causing an insulin surge. Fig. 5. Intra-operative findings; (A) Insulinoma at the tail of pancreas near splenic hilum, (B) pancreas, (C) Spleen, (D) surgical specimen of enucleated insulinoma. A two-fold rise in the insulin levels above the baseline localizes the insulinoma to the anatomic region perfused by the injected artery. Fortunately, this study facilitated local- sitivity of contrast CT and MRI has been reported to range between 33-64% and 40-90%, respectively. 4,5 This varia- bility is likely dependent on tumour size, type of machine, protocols used and the expertise of radiologist. ization of the tumour to the distal body or tail in this patient. Preoperative knowledge of the pancreatic segment containing the insulinoma facilitates directed visual examina- Duminda Subasinghe, et al. Occult sporadic insulinoma 237 tion and palpation to locate the tumour. Despite this, the SSCG. Formal analysis: DS, SSCG, SS. Methodology: tumour proved to be elusive and was only located nestled DS, SSCG, SS. Project administration: DS, SSCG, VED, in the tail within the splenic hilum using IOUS. IOUS in CG, EG, CA, NPS, SS. Visualization: DS, SSCG, VED, combination with intraoperative palpation by an experi- CG, EG, CA, NPS, SS. Writing - original draft: DS, enced operator has been shown to achieve excellent de- SSCG. Writing - review & editing: DS, SSCG, SS. 15,16 tection rates of 80-100%. Recurrence rates for sporadic insulinoma after surgery is 5% at 10 years and 7% at 20 years. 17 REFERENCES Therefore our patients likelihood of recurrence is very low. The patient was well and normoglycaemic more than a year after surgery. In conclusion, preoperative localization of insulinomas is mandatory to achieve good results with minimum morbidity. SACS is an invaluable adjunct when cross-sectional imaging fails to do this. IOUS, visualization and palpation during surgical exploration compliment preoperative localization. Timely referral to tertiary centres equipped with multidisciplinary expertise improves outcomes. CONFLICT OF INTEREST The authors declare that they have no competing interests. ORCID Duminda Subasinghe: https://orcid.org/0000-0003-1805-1589 Sonali Sihindi Chapa Gunatilake: https://orcid.org/0000-0003-0636-350X Vihara Erangika Dassanyake: https://orcid.org/0000-0001-6582-0577 Chaminda Garusinghe: https://orcid.org/0000-0001-5432-2038 Eranga Ganewaththa: https://orcid.org/0000-0003-4086-3639 Chinthaka Appuhamy: https://orcid.org/0000-0002-1716-9721 Noel P. Somasundaram: https://orcid.org/0000-0002-6241-7501 Sivasuriya Sivaganesh: https://orcid.org/0000-0002-6874-6904 AUTHOR CONTRIBUTIONS Conceptualization: DS, SSCG, SS. Data curation: DS, 1. Bilimoria KY, Talamonti MS, Tomlinson JS, Stewart AK, Winchester DP, Ko CY, et al. Prognostic score predicting survival after resection of pancreatic neuroendocrine tumors: analysis of 3851 patients. Ann Surg 2008;247:490-500. 2. Abboud B, Boujaoude J. Occult sporadic insulinoma: localization and surgical strategy. World J Gastroenterol 2008;14:657-665. 3. Barts Endocrinology. 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