Nonfunctioning PanNETs represent 30–50 % of all PanNETs, malignancy occurs in 60–90 % [13–15], and long-term survival can be achieved in many patients [16]. Pancreatic resections differ according to tumor site: lesions of the pancreatic head are treated with a pancreaticoduodenectomy while lesions of the body and tail with a distal pancreatectomy. Functional impairment of the organ due to the loss of parenchyma is a general risk of major pancreatic resections, resulting in exocrine and/or endocrine insufficiency. When tumors occur in the neck, they can be removed through a parenchyma-sparing operation called “middle” or “central” pancreatectomy [17]. There is the possibility of leaks from both the closed-cut edge of the head and the pancreaticojejunostomy , considering that in most patients, we are dealing with a normal soft pancreatic texture with a small Wirsung’s duct. Enucleation is a feasible procedure for the radical treatment of benign and borderline pancreatic neoplasms [18] and is associated with long-term survival, despite a relatively high risk of pancreatic fistula formation [19, 20]. Before enucleating a PanNET, it is important to consider where the tumor is located in relation to the main pancreatic duct, as enucleations of tumors located very close to this may result in damage to the pancreatic duct and subsequent pancreatic leakage. Clear negative margins cannot be obtained after both enucleation and intermediate resection, and a standard lymphadenectomy is not usually performed [21]. On the other hand, tumor enucleation is associated with shorter operative time, less intraoperative blood loss, and shorter hospital stay compared to pancreaticoduodenectomy and distal pancreatectomy [18]. The main advantage for atypical resections is that they are associated with a lower risk of long-term endocrine/exocrine impairment when compared to standard resections [22]. In the presence of multifocal disease, a total pancreatectomy is the treatment of choice.

Functioning PanNETs are often small in size, and localization may be difficult also due to their possible extra duodenal-pancreatic origin (for gastrinomas) as jejunum, stomach, mesentery, spleen, and ovaries. They primarily include insulinomas and gastrinomas , with an incidence of 70–80 % and 20–25 % of all PanNETs, and an incidence of malignancy of <10 % and 50–60 %, respectively [14]. Insulinoma is one of the most frequent functioning PanNET. It is generally solitary, benign, and curable with surgery [14, 23, 24]. Recurrence after resection occurs in about 3 % of cases [25]. The procedures of choice are enucleation for small and isolated insulinomas and partial pancreatectomy for large and potentially malignant insulinomas [26]. Besides enucleation, middle pancreatectomy is an alternative parenchyma-sparing technique for this tumor entity [27]. Also, laparoscopic management of insulinoma in the body and tail of the pancreas, with distal pancreatectomy or enucleation, is widely accepted and used [28]. In the case of occult insulinoma, blind distal pancreatectomy should be avoided [29]. However, explorative surgery with intraoperative ultrasound may be indicated in cases where preoperative diagnostics could not reveal any pancreatic lesion, as this is an excellent method for identifying occult insulinoma [30] (see also Chap. 2).

Most gastrinomas are located in the “gastrinoma triangle,” which comprises the head of the pancreas and the first and second parts of the duodenum [31]. Gastrinoma is associated with gastric ulcerations due to overproduction of gastrin [32]. The clinical presentation of gastrinoma is referred to as Zollinger-Ellison syndrome. With the introduction of proton pump inhibitors, which prevent ulcer formation, surgery changed from being a symptomatic treatment to curative treatment in patients with Zollinger-Ellison syndrome [23]. All patients with Zollinger-Ellison syndrome without multiple neuroendocrine neoplasia type 1 or metastatic disease should be offered surgical exploration for possible cure [33]. The extent of surgery is a highly controversial issue in gastrinoma [34]. This is especially true for duodenal gastrinomas. Several groups suggested that duodenotomy with excision of duodenal wall gastrinomas, enucleation of any head gastrinomas, and peripancreatic lymph node dissection with or without distal pancreatic resection is the adequate procedure for duodenal gastrinoma [35]. Other groups, as well as the authors, choose pancreaticoduodenectomy as the first-line procedure for duodenal gastrinoma, because it is very likely that proliferative gastrin cells in the normal duodenal mucosa are the precursors of these tumors, and, for this reason, long-term cure is only possible if the organ of origin is removed. Moreover, a standard pancreaticoduodenectomy allows to perform a standard lymphadenectomy in a disease where lymph node metastases are very frequent. The incidences of other functioning PanNETs, such as vasoactive intestinal peptide-producing tumors (VIPoma), glucagonoma, and somatostatinoma, are very low. These patients should undergo tumor resection to correct the severe hormonally caused metabolic derangements [23].