Surgical treatment of pancreatic endocrine tumors in MEN1 Machado MCC parathyroid auto-implant in patients with MEN1 is beneficial to the metabolic status, but it also leads to decreasing secretion of several hormones, such as gastrin, which in turn may cause a significant improvement of the clinical symp- toms secondary to the hormonal excess (5–7). Parathyroidec- tomy in MEN1 should therefore be performed before operation for PETs, apart from in insulinoma. As mentioned, surgical strategies applied to PETs/MEN1 differ greatly from the usual approaches used in patients with S-PETs. Clinical and genetic diagnosis of MEN1 should be made or ruled out before surgery in each patient with MEN1, as reported previously (3,8). This procedure will allow the identification of the best surgical approach to each individual case of PET, which may potentially lead to lower morbidity and mortality rates in patients with PET- associated MEN1. We also performed methodical screening for the MEN1 tumor suppressor gene in our MEN1 families, which should allow the early diagnosis and treatment of MEN1 in relatives carrying MEN1 germline mutations and a trend towards lower morbidity rates (9). PREOPERATIVE EVALUATION Computed tomography, magnetic resonance imaging, and ultrasonography can miss PETs,1 cm. Octreotide scintigraphy is an efficient diagnostic tool but this depends on the size of the lesion and the presence of somatostatin receptors in the tumor cells. Recently, gallium-labeled somatostatin analog peptide has been used to detect MEN1-related tumors (10). Endoscopic ultrasonography is the most useful tool for tumor diagnosis and localization in PETs/MEN1, as well as for depiction of the anatomic relationship with the main pancreatic duct, which is important for the proper surgical treatment. Endoscopic ultrasonography is able to detect PETs,1 cm, allowing early diagnosis (Figure 1). Invasive techniques for the diagnosis and localization of gastrinomas or insulinomas have been reported, although their accuracy has not been reproduced in all centers (11). Furthermore, in our experience, intraoperative palpation, inspection, and ultrasonography are efficient tools to localize most lesions (11). Figure 1 - Endoscopic ultrasonography. Arrow shows a small pancreatic neuroendocrine tumor. 146 CLINICS 2012;67(S1):145-148 NON-FUNCTIONING PETS In a recent study, Goudet et al. (12) verified that PETs, including the non-functioning PETs, and thymic carcinoids are frequent causes of death in patients with MEN1. At diagnosis, non-functioning PETs are frequently malig- nant, usually larger and with a worse prognosis than functioning PETs. Tumor size was positively correlated with malignancy and lesions .2.0 cm have been reported to have a higher risk for malignancy (13). In addition, other authors showed that non-functioning PETs with diameters .1.0 cm are already prone to metastasize (14). Based on these findings, pancreatic resection associated with lymphadenect- omy has been recommended in these cases (14). Moreover, as liver metastases are frequently found in PETs.1.0 cm, these tumors should be carefully investigated and operated on as soon as possible (12,14). Concordantly, extended distal pancreatectomy associated with enucleation of PETs.1 cm located at the pancreatic head has also been recommended, in an attempt to prevent liver metastases (15). Conversely, total pancreatectomy, associated or not with duodenectomy, has not been indicated because of the possible decrease in the patient’s quality of life, although this surgical intervention may be used in selected PET/ MEN1 patients (16). GASTRINOMAS The vast majority of sporadic gastrinomas are represented by single tumors located at the pancreas and the current surgical approach to these lesions is tumor enucleation. Conversely, the majority of gastrinomas/MEN1 are multiple, asynchronic tumors mostly spread throughout the duodenum and less frequently found in the pancreas. These frequently malignant tumors (,60%) are mostly associated with multiple and small gastric carcinoids (1,3,14). Controversies related to the surgical approach to gastri- noma/MEN1 may exist and are mostly related to the timing and extension of the surgical procedure. These tumors usually have an unpredictable course, difficult preoperative localization and present as multiple duodenal tumors. Although PETs usually lead to limited survival, some patients with metastatic PETs may survive for long periods of time with clinical treatment. Some authors recommend surgical treatment only for cases with gastrinomas/MEN1 .3.0 cm, whereas others indicate an early surgical intervention for all gastrinoma/ MEN1 patients, as soon as the diagnosis is made (14,17–19). This controversy may be related to the fact that there appear to be two different patterns of gastrinomas in MEN1 patients: the first tend to have an indolent course with or without metastasis, whereas the second pattern is charac- terized by rapid tumor progression. Although there are no definite markers for the adequate identification of these two potential gastrinoma subsets, the aggressiveness of these tumors could be evaluated by the following parameters: serum levels of gastrin, tumor histological differentiation, Ki-67 positivity, a high mitotic number, and the presence of progesterone receptors, as reported recently (19). Pancreatoduodenectomy with regional lymphadenectomy Limited surgical resection with excision of duodenal tumors, excision of pancreatic cephalic lesions, and distal