Resection Of Pancreatic Neuroendocrine Tumors Research Articles

Retrospective study evaluating factors influencing cancer recurrence following surgical resection of pancreatic neuroendocrine tumours (PanNETs)

Retrospective study evaluating factors influencing cancer recurrence following surgical resection of pancreatic neuroendocrine tumours (PanNETs)

Retrospective audit evaluating outcomes in patients post resection for pancreatic neuroendocrine tumours

Retrospective audit evaluating outcomes in patients post resection for pancreatic neuroendocrine tumours

A novel model for predicting postoperative liver metastasis in R0 resected pancreatic neuroendocrine tumors: integrating computational pathology and deep learning-radiomics

BackgroundPostoperative liver metastasis significantly impacts the prognosis of pancreatic neuroendocrine tumor (panNET) patients after R0 resection. Combining computational pathology and deep learning radiomics can enhance the detection of postoperative liver metastasis in panNET patients.MethodsClinical data, pathology slides, and radiographic images were collected from 163 panNET patients post-R0 resection at Fudan University Shanghai Cancer Center (FUSCC) and FUSCC Pathology Consultation Center. Digital image analysis and deep learning identified liver metastasis-related features in Ki67-stained whole slide images (WSIs) and enhanced CT scans to create a nomogram. The model’s performance was validated in both internal and external test cohorts.ResultsMultivariate logistic regression identified nerve infiltration as an independent risk factor for liver metastasis (p < 0.05). The Pathomics score, which was based on a hotspot and the heterogeneous distribution of Ki67 staining, showed improved predictive accuracy for liver metastasis (AUC = 0.799). The deep learning-radiomics (DLR) score achieved an AUC of 0.875. The integrated nomogram, which combines clinical, pathological, and imaging features, demonstrated outstanding performance, with an AUC of 0.985 in the training cohort and 0.961 in the validation cohort. High-risk group had a median recurrence-free survival of 28.5 months compared to 34.7 months for the low-risk group, showing significant correlation with prognosis (p < 0.05).ConclusionA new predictive model that integrates computational pathologic scores and deep learning-radiomics can better predict postoperative liver metastasis in panNET patients, aiding clinicians in developing personalized treatments.

Minimally invasive versus open distal pancreatectomy for resectable pancreatic neuroendocrine tumors: A propensity score matched multicentric comparative French study

BackgroundMinimally invasive surgery has gained momentum for left pancreatic resections. However, debate remains about whether it has any advantage over open surgery for distal pancreatectomy for pancreatic neuroendocrine tumors. MethodsThis retrospective review examined pancreatectomies performed for resectable pancreatic neuroendocrine tumors at 21 centers in France between January 2014 and December 2018. Short and long-term outcomes were compared before and after propensity score matching based on tumor size, sex, age, body mass index, center, and method of pancreatic transection. ResultsDuring the period study, 274 patients underwent left pancreatic resection for pancreatic neuroendocrine tumors [109 underwent distal splenopancreatectomy, and 165 underwent spleen-preserving distal pancreatectomy [(splenic vessel preservation (n = 97; 58.7%)/splenic vessel resection (n = 68; 41.3%)]. Before propensity score matching, minimally invasive surgery was associated with a lower rate of major morbidity (P = .004), lower rate of postoperative delayed gastric emptying (P = .04), and higher rate of “textbook” outcomes (P = .04). After propensity score matching, there were 2 groups of 54 patients (n = 30 distal splenopancreatectomy; n = 78 spleen-preserving distal pancreatectomy). Minimally invasive surgery was associated with less blood loss (P = .05), decreased rate of major morbidity (6% vs. 24%; P = .02), less delayed gastric emptying (P = .05) despite similar rates of postoperative fistula, hemorrhage, and reoperation (P > .05). The 5-year overall survival (79% vs. 75%; P = .74) and recurrence-free survival (10% vs 17%; P = .39) were similar. ConclusionMinimally invasive surgery for left pancreatic resection can be safely proposed for patients with resectable left pancreatic neuroendocrine tumors. Minimally invasive surgery decreases the rate of major complications while providing comparable long-term oncologic outcomes.

National practice patterns in the use of endoscopic ultrasound biopsy for resectable Pancreatic Neuroendocrine Tumors: Insights into the role of DOTATATE PET/CT in diagnosis

IntroductionPancreatic neuroendocrine tumors (PNETs) are typically diagnosed using endoscopic ultrasound-guided (EUS) biopsy, which can be associated with complications. Since 2016, DOTATATE PET/CT has emerged as an effective tool to localize and stage PNETs. MethodsPatients with PNETs who underwent R0 resections were identified from the 2004–2019 National Cancer Database PUF. Joinpoint regression and multivariable logistic regression were used to analyze trends in the use of biopsy. ResultsOf 16,746 R0 resected PNET patients, 44 ​% underwent diagnostic biopsy. Joinpoint regression showed a significant increase in the use of biopsy from 2004 to 2019 (APC 1.80, p ​< ​0.001). A higher percentage of patients diagnosed after DOTATATE approval underwent biopsy compared to those diagnosed before (48 ​% vs. 42 ​%, p ​< ​0.001). Adjusted analysis showed diagnosis after 2016 was associated with increased odds of biopsy (OR ​= ​1.67, p ​< ​0.001). ConclusionsDespite technologic advancement with DOTATATE PET/CT, there has been a significant increase in the proportion of resectable PNETs undergoing preoperative biopsy.

Minimally invasive versus open distal pancreatectomy for resectable pancreatic neuroendocrine tumors: a propensity score matched multicentric comparative study

Minimally invasive versus open distal pancreatectomy for resectable pancreatic neuroendocrine tumors: a propensity score matched multicentric comparative study

Real-time prospective DAXX/ATRX testing of 186 consecutive surgically resected pancreatic neuroendocrine tumors reveals loss of expression correlates with distant metastasis

Real-time prospective DAXX/ATRX testing of 186 consecutive surgically resected pancreatic neuroendocrine tumors reveals loss of expression correlates with distant metastasis

Prognostic role and predictors of lymph node involvement in pancreatic neuroendocrine tumors

PurposeTo define the prognostic role of lymph node involvement (LNI) in patients with pancreatic neuroendocrine tumors (PNETs) and identify predictors of LNI using a comprehensive multifactor analysis focusing on preoperative radiological features. MethodsThis study included 236 patients with preoperative computed tomography who underwent radical surgical resection of PNETs at our hospital between 2009 and 2019. Univariate and multivariable logistic regression analyses were performed to investigate the risk factors associated with LNI and tumor recurrence. The disease-free survival (DFS) rates with and without LNI were compared. ResultsForty-four of the 236 patients (18.6%) had LNI. Biliopancreatic duct dilatation (odds ratio [OR], 2.295; 95% confidence interval [CI], 1.046–5.035; p = 0.038), tumor margin (OR, 2.189; 95% CI, 1.034–4.632; p = 0.041), and WHO grade (G2: OR, 2.923; 95% CI, 1.005–8.507; p = 0.049; G3: OR, 12.067; 95% CI, 3.057–47.629; p < 0.001) were independent risk factors of LNI in PNETs. Multivariable analysis showed that LNI (OR, 2.728; 95% CI, 1.070–6.954; p = 0.036), G3 (OR, 4.894; 95% CI, 1.047–22.866; p = 0.044), and biliopancreatic duct dilatation (OR, 2.895; 95% CI, 1.124–7.458; p = 0.028) were associated with PNET recurrence in patients after surgery. Patients with LNI had a significantly worse DFS than those without LNI (3‐year DFS: 85.9 vs. 96.7%; p < 0.001; 5‐year DFS: 65.1 vs. 93.9%; p < 0.001). ConclusionLNI was associated with decreased DFS. Biliopancreatic duct dilatation, irregular tumor margins, and grades G2 and G3 were independent risk factors for LNI.

Simultaneous compared to staged resection of metastatic PNET is associated with increased morbidity

Background: Between 40-80% of pancreatic neuroendocrine tumors (PNET) will present with liver metastasis. Liver resection/debulking of metastatic PNET has been shown to improve long-term survival. However, there is a paucity of data on the morbidity associated with simultaneous compared to staged liver and pancreatic resection for PNETs.

ASO Visual Abstract: Calcifications and Cystic Morphology on Preoperative Imaging Predict Survival After Resection of Pancreatic Neuroendocrine Tumors.

ASO Visual Abstract: Calcifications and Cystic Morphology on Preoperative Imaging Predict Survival After Resection of Pancreatic Neuroendocrine Tumors.

Recurrence and outcomes of non‐functional pancreatic neuroendocrine tumours post‐resection: an Australian retrospective, multicentre cohort study

Pancreatic neuroendocrine tumours (PNETs) are heterogenous entities with variable clinical outlook. The prevalence of PNETs is increasing in Australia. Despite this, data on peri-operative management and post-operative prognosis for Australian patients is scant in the literature. Patients from two tertiary hospitals in Victoria were recruited. Inclusion criteria included patients who underwent curative surgical resection for primary, non-functioning, PNETs without metastases from January 2011 to December 2021. Patients were identified via histopathological reports, CMBS and ICD-10 codes. Data were sourced from Electronic Medical Records, outpatient notes and letters. Sixty-three patients (34 Male, 29 Female) underwent surgical resection for PNETs. Fifty-three patients (84.1%) had a post-operative complication, and 21 (33.3%) had severe complications. Two patients had disease recurrence. Head PNETs had higher Ki-67% (5.33 vs. 2.72, P=0.29), and likelihood of nodal spread (9 (36%) vs. 4 (16%), P=0.054). Pancreatic Head resections were also associated with more frequent ICU admissions (21 (84%) vs. 18 (54.5), P=0.024), longer ICU stays (4.05 vs. 2.17 days, P=0.10) and hospital stays (26.76 vs. 8.27 days, P=<0.001). Within the limitations of this study, it demonstrates that surgical resection of PNET carries a significant morbidity with a low rate of recurrence. Additionally, Pancreatic head NETs may be associated with higher grades and increased likelihood of nodal metastases. Considering this, careful patient selection is paramount.

Calcifications and Cystic Morphology on Preoperative Imaging Predict Survival After Resection of Pancreatic Neuroendocrine Tumors.

Radiographic calcifications and cystic morphology are associated with higher and lower tumor grade, respectively, in pancreatic neuroendocrine tumors (PNETs). Whether calcifications and/or cystic morphology could be used preoperatively to predict post-resection survival in patients with PNETs remains elusive. Patients undergoing curative-intent resection of well-differentiated PNETs from 2000 to 2017 at eight academic institutions participating in the US Neuroendocrine Tumor Study Group were identified. Preoperative cross-sectional imaging reports were reviewed to identify the presence of calcifications and of a cystic component occupying >50% of the total tumor area. Clinicopathologic characteristics and recurrence-free survival (RFS) were compared. Of 981 patients studied, 18% had calcifications and 17% had cystic tumors. Tumors with calcifications were more commonly associated with Ki-67 ≥3% (47% vs. 33%; p=0.029), lymph node metastasis (36% vs. 24%; p=0.011), and distant metastasis (13% vs. 4%; p<0.001). In contrast, cystic tumors were less commonly associated with lymph node metastasis (12% vs. 30%; p<0.001). Five-year RFS after resection was most favorable for cystic tumors without calcifications (91%), intermediate for solid tumors without calcifications (77%), and least favorable for any calcified PNET (solid 69%, cystic 67%; p=0.043). Calcifications remained an independent predictor of RFS on multivariable analysis (p=0.043) controlling for nodal (p<0.001) and distant metastasis (p=0.001). Easily detectable radiographic features, such as calcifications and cystic morphology, can be used preoperatively to stratify prognosis in patients with PNETs and possibly inform the decision to operate or not, as well as guide the extent of resection and potential use of neoadjuvant therapy.

Predictors of post-operative pancreatic fistula formation in pancreatic neuroendocrine tumors: A national surgical quality improvement program analysis

BackgroundPost-operative pancreatic fistula (POPF) is a serious complication following pancreas surgery. We aimed to establish factors associated with POPF specifically in patients with pancreatic neuroendocrine tumors (PNET). MethodsThe 2014–2018 American College of Surgeons National Surgical Quality Improvement Program database was querried for patients undergoing resection for PNET. The impact of patient, tumor, and operative factors on POPF formation was evaluated. Results3532 patient underwent resections for PNET. The POPF rate was significantly higher in patients with PNET (24.8%) versus non-PNET (16.4%) (p < 0.0001). Male sex (OR 1.45, 95% CI 1.11–1.89), enucleation (OR 3.14, 95% CI 1.10–8.98), pancreaticoduodenectomy (OR 1.51, 95% CI 1.13–2.03), small duct size <3 mm (OR 3.24, 95% CI 1.62–6.48), and soft gland texture (OR 1.81, 95% CI 1.18–2.77) were independently associated with POPF in PNET patients on multivariable analysis. ConclusionsPOPF is more common in patients undergoing resection for PNET and is dictated primarily by surgical approach and gland characteristics.

Sporadic nonfunctional pancreatic neuroendocrine tumors: Risk of lymph node metastases and aggressiveness according to tumor size: A multicenter international study

BackgroundAlthough the correlation between tumor size and aggressiveness is clearly established in sporadic nonfunctional pancreatic neuroendocrine tumors, the management of tumors ≤2 cm remains debated. In recent guidelines, the cut-off size to operate ranged from 1 to 2 cm. The aim of this retrospective study was to report the rate of lymph nodes metastases in resected sporadic nonfunctional pancreatic neuroendocrine tumors, according to tumor size and, second, to identify risk factors of lymph node metastases and disease-free survival. MethodsResected sporadic nonfunctional pancreatic neuroendocrine tumors from 9 international expert centers were included (1999–2017). Functional pancreatic neuroendocrine tumors, genetic syndromes, and R2 resection were excluded. Aggressiveness was defined as microvascular invasion, perineural invasion, lymph node metastases, G3 grading, distant metastases, and/or recurrence. ResultsOverall, 495 resected sporadic nonfunctional pancreatic neuroendocrine tumors were included. For tumors up to 5 cm, the risk of lymph node metastases was increased by 1.73 for every 1 cm increase in size (odds ratio = 1.73; 95% confidence interval = 1.46–2.03). Tumor size >2 cm (P < .001), perineural invasion (P = .002), microvascular invasion (P < .001), and distant metastases (P = .008) were independently associated with lymph node metastases. Tumor size >2 cm (P = .003), R1 status (P = .004), lymph node metastases (P < .001), and World Health Organization grade 3 (P = .002) were independently associated with disease-free survival. Aggressiveness rate was 13.1% in tumors ≤1 cm and 29% in tumors between 1.1 and 2 cm. ConclusionIn resected sporadic nonfunctional pancreatic neuroendocrine tumors, the risk of lymph node metastases is correlated to tumor size. Considering that sporadic nonfunctional pancreatic neuroendocrine tumors between 1.1 and 2 cm had a higher risk of lymph node metastases and recurrence compared to tumors ≤1 cm, the decision to perform surgery in this subgroup of patients should be individualized in surgically fit patients.

Clinical features and postoperative survival in patients with sporadic versus multiple endocrine neoplasia type 1-related pancreatic neuroendocrine tumors: An international cohort study

BackgroundThe optimal surgical management of pancreatic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1 is controversial. This study sought to compare clinicopathologic characteristics and outcomes of multiple endocrine neoplasia type 1–associated and sporadic pancreatic neuroendocrine tumors from a large multi-national database. MethodsA multi-institutional, international database of patients with surgically resected pancreatic neuroendocrine tumors was analyzed. The cohort was divided into 2 groups: those with multiple endocrine neoplasia type 1 versus those with sporadic disease. Clinicopathologic comparisons were made. Overall and disease-free survival were analyzed. Propensity score matching was used to reduce bias. ResultsOf 651 patients included, 45 (6.9%) had multiple endocrine neoplasia type 1 and 606 sporadic pancreatic neuroendocrine tumors. Multiple endocrine neoplasia type 1–associated pancreatic neuroendocrine tumors were more common in younger patients and associated with multifocal disease at the time of surgery and higher T-stage. Lymph node involvement and the presence of metastasis were similar. Total pancreatectomy rate was 5-fold higher in the multiple endocrine neoplasia type 1 cohort. Median survival did not differ (disease-free survival 126 months multiple endocrine neoplasia type 1 vs 198 months sporadic, P > .5). After matching, survival remained similar (overall survival not reached in either cohort, disease-free survival 126 months multiple endocrine neoplasia type 1 vs 198 months sporadic, P > .5). Equivalence in overall survival and disease-free survival persisted even when patients who underwent subtotal and total pancreatectomy were excluded. ConclusionMultiple endocrine neoplasia type 1–associated pancreatic neuroendocrine tumors are more common in younger patients and are associated with multifocality and higher T-stage. Survival for patients with multiple endocrine neoplasia type 1–associated pancreatic neuroendocrine tumors is comparable to those with sporadic pancreatic neuroendocrine tumors, even in the absence of radical pancreatectomy. Consideration should be given to parenchymal-sparing surgery to preserve pancreatic function.

Value of lymphadenectomy in patients with surgically resected pancreatic neuroendocrine tumors

BackgroundAlthough some factors that predict the prognosis in pancreatic neuroendocrine tumor (pNET) have been confirmed, the predictive value of lymph node metastasis (LNM) in the prognosis of pNETs remains conflicting and it is not clear whether regional lymphadenectomy should be performed in all grades of tumors.MethodsWe included pNET patients undergoing surgery in Shanghai pancreatic cancer institute (SHPCI). The risk factors for survival were investigated by the Kaplan–Meier method and Cox regression model. We evaluated the predictors of LNM using Logistic regression.ResultsFor 206 patients in the SHPCI series, LNM was an independent prognostic factor for entire cohort suggested by multivariate Cox regression analysis. LNM (P = 0.002) predicted poorer overall survival (OS) in grade 2/3 cohort, but there is no significant association between LNM and OS in grade 1 cohort. Grade (P < 0.001) and size (P = 0.049) predicted LNM in entire cohort. Grade (P = 0.002) predicted LNM while regardless of size in grade 2/3 cohort.ConclusionsBased on our own retrospective data obtained from a single center series, LNM seems to be associated with poorer outcome for patients with grade 2/3 and/or grade 1 > 4 cm tumors. On the other way, LNM was seems to be not associated with prognosis in patients with grade 1 tumors less than 4 cm. Moreover, tumor grade and tumor size seem to act as independent predictors of LNM. Thus, regional lymphadenectomy should be performed in grade 2/3 patients but was not mandatory in grade 1 tumors < 4 cm. It is reasonable to perform functional sparing surgery for grade 1 patients or propose a clinical-radiological monitoring.

Surgical Indications and Outcomes of Resection for Pancreatic Neuroendocrine Tumors with Vascular Involvement.

Simple SummaryPancreatic neuroendocrine tumors (pNETs) are a heterogenous group of rare epithelial neoplasms. For most patients, surgery remains the only treatment modality to cure pNETs, and is recommended for patients with surgically resectable disease. Many of these tumors are non-functional tumors and do not produce clinical symptoms, so patients may present with locally advanced tumors, which invade surrounding organs or neighboring blood vessels. The presence of vascular involvement had previously been considered a contraindication to surgery, but, in recent years, at centers with considerable experience, aggressive surgery to remove pNETs with vascular reconstruction has been performed safely and with good long-term survival. In this review, we will discuss the considerations for resectability, review novel surgical approaches, and present the available evidence on the immediate and long-term postoperative outcomes.Complete surgical resection of pancreatic neuroendocrine tumors (pNETs) has been suggested as the only potentially curative treatment. A proportion of these tumors will present late during disease progression, and invade or encase surrounding vasculature; therefore, surgical treatment of locally advanced disease remains controversial. The role of surgery with vascular reconstruction in pNETs is not well defined, and there is considerable variability in the use of aggressive surgery for these tumors. Accurate preoperative assessment is critical to evaluate individual considerations, such as anatomical variants, areas and lengths of vessel involvement, proximal and distal targets, and collateralization secondary to the degree of occlusion. Surgical approaches to address pNETs with venous involvement may include thrombectomy, traditional vein reconstruction, a reconstruction-first approach, or mesocaval shunting. Although the amount of literature on pNETs with vascular reconstruction is limited to case reports and small institutional series, the last two decades of studies have demonstrated that aggressive resection of these tumors can be performed safely and with acceptable long-term survival.

Minimally Invasive vs Open Pancreatectomy for Pancreatic Neuroendocrine Tumors: Multi-Institutional 10-Year Experience of 1,023 Patients.

Resection of pancreatic neuroendocrine tumors (PNETs) may be associated with adverse perioperative outcomes compared with pancreatic adenocarcinoma given the high-risk nature of soft glands with small pancreatic ducts. The effect of minimally invasive surgery (MIS) pancreatectomy on outcomes of PNETs remains to be examined, which is the aim of this study. Between 2009 and 2019, 1,023 patients underwent pancreatectomy for PNETs at 4 institutions. Clinicopathologic data and perioperative outcomes of patients who underwent MIS (n = 447) and open resections (n = 576) were compared. Of the 1,023 patients, 51% were male, the mean age was 58, the median tumor size was 2.1 cm, and 73% were grade 1 PNETs. There were 318 (31%) pancreatoduodenectomies (PDs), 541 (53%) distal pancreatectomies (DPs), 80 (7.8%) enucleation (ENs), 72 (7%) central pancreatectomies (CPs), and 12 (1.2%) total pancreatectomies. Almost half of the patients (N = 447, 44%) had MIS operations, of which 230 (51%) were robotic and 217 (49%) were laparoscopic. Compared with open operations, MIS PDs had significantly lower operative blood loss (150 vs 400 mL, p < 0.001) and rate of clinically relevant postoperative pancreatic fistulas (CR-POPFs; 13% vs 27%, p = 0.030), and MIS DPs had a shorter length of stay (5 vs 6 days, p < 0.001). Although MIS DPs and ENs had CR-POPFs comparable with open operations, MIS CPs had a higher CR-POPF rate (45% vs 15%, p = 0.013). After adjusting for pathological differences, MIS pancreatectomy was associated with recurrence-free survival and overall survival comparable with open pancreatectomy. MIS pancreatectomy for PNETs is associated with improved outcomes or outcomes comparable with open resection.

Similar Outcomes in Minimally Invasive versus Open Management of Primary Pancreatic Neuroendocrine Tumors: A Regional, Multi-Institutional Collaborative Analysis.

Simple SummaryPancreatic neuroendocrine tumors (PNETs) are rare tumors of the pancreas that are often curable with surgery. Due to their rarity, it is difficult to study whether newer techniques for removing PNETs, specifically minimally invasive surgeries, are as safe and effective as open surgeries in these patients. In this study, we pooled the experience of multiple high-volume institutions who remove PNETs, and studied outcomes in open and minimally invasive surgeries. We discovered that patients receiving a minimally invasive surgery were equally likely to remain alive and without disease as patients receiving an open surgery. Additionally, there was no difference in the most common complications experienced by patients receiving these operations. Therefore, we can recommend the routine use of minimally invasive surgery techniques in appropriately selected patients with PNET, if offered by their surgeon.In pancreatic neuroendocrine tumors (PNETs), the impact of minimally invasive (MI) versus open resection on outcomes remains poorly studied. We queried a multi-institutional pancreatic cancer registry for patients with resected non-metastatic PNET from 1996–2020. Recurrence-free (RFS), disease-specific survival (DSS), and operative complications were evaluated. Two hundred and eighty-two patients were identified. Operations were open in 139 (49%) and MI in 143 (51%). Pancreaticoduodenectomy was performed in 77 (27%, n = 23 MI), distal pancreatectomy in 184 (65%, n = 109 MI), enucleation in 13 (5%), and total pancreatectomy in eight (3%). Median follow-up was 50 months. Thirty-six recurrences and 13 deaths from recurrent disease yielded 5-year RFS and DSS of 85% and 95%, respectively. On multivariable analysis, grade 1 (HR 0.07, p < 0.001) and grade 2 (HR 0.20, p = 0.002) tumors were associated with improved RFS, while T3/T4 tumors were associated with worse RFS (OR 2.78, p = 0.04). MI resection was not associated with RFS (HR 0.53, p = 0.14). There was insufficient mortality to evaluate DSS with multivariable analysis. Of 159 patients with available NSQIP data, incisional surgical site infections (SSIs), organ space SSIs, Grade B/C pancreatic fistulas, reoperations, and need for percutaneous drainage did not differ by operative approach (all p > 0.2). Nodal harvest was similar for MI versus open distal pancreatectomies (p = 0.16) and pancreaticoduodenectomies (p = 0.28). Minimally invasive surgical management of PNETs is equivalent for oncologic and postoperative outcomes.

Simultaneous Resection of Pancreatic Neuroendocrine Tumors with Synchronous Liver Metastases: Safety and Oncological Efficacy.

Simple SummaryUp to half of all newly diagnosed pancreatic neuroendocrine tumors (PNET) present with liver metastases (LM). The surgical resection of PNETs and LMs can provide complete tumor clearance and improve long-term survival. However, the combination of liver and pancreatic resection simultaneously can theoretically cumulate the morbidity and mortality of two separate operations. In the current study, we analyzed the outcomes of the synchronous surgical resection of PNETs and LMs in 51 patients. There were no differences in the postoperative outcomes in terms of mortality and morbidity according to the type of pancreatic resection. The tumor grade was identified as the sole prognostic factor for survival. The resection of well-differentiated PNETs with LMs was characterized by the longest survival rates (median overall survival 128 months, 5-year overall survival 83%). The optimal sequential surgical strategies for PNETs with LM and the use of neoadjuvant/adjuvant chemotherapy in this category of patients remain to be further investigated. Whether the simultaneous resection of pancreatic neuroendocrine tumors (PNET) with synchronous liver metastases (LM) is safe and oncologically efficacious remains to be debated. We retrospectively reviewed clinical data from patients who underwent the simultaneous resection of PNETs with LMs over the last 25 years. Fifty-one consecutive patients with a median age of 54 years (range 27–80 years) underwent pancreaticoduodenectomy (PD) (n = 16), distal pancreatosplenectomy (DSP) (n = 32) or total pancreatectomy (n = 3) with synchronous LM resection. There were no differences in the postoperative outcomes in term of mortality (p = 0.33) and morbidity (p = 0.76) between PD and DSP. The median overall survival (OS) was 64.78 months (95% CI: 49.7–119.8), and the overall survival rates at 1, 3, and 5 years were 97.9%, 86.2% and 61%, respectively. The OS varied according to the tumor grade (G): G1 (OS 128 months, 5-year OS 83%) vs. G2 (OS 60.5 months, 5-year OS 58%) vs. G3 (OS 49.7 months, 5-year OS 0%) (p = 0.03). Multivariate Cox analysis identified G as the only prognostic factor (HR: 5.56; 95% CI: 0.91–9.60; p = 0.01). Simultaneous PNETS with LMs can be performed safely with acceptable morbidity and mortality at tertiary centers. Well-differentiated PNETs had longer survival and might benefit the most from these extended surgeries.