Small Nonfunctional Pancreatic Neuroendocrine Tumors Research Articles

Long-term Follow-up of Small Nonfunctioning Pancreatic Neuroendocrine Tumors Diagnosed Using Endoscopic Ultrasound-guided Fine-needle Aspiration.

Objective Clinical practice guidelines in Japan recommend surgery for all nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs), regardless of their size or associated symptoms. Because pancreatic resection is highly invasive, follow-up for small NF-PNETs is often chosen in clinical practice. However, the natural history of NF-PNET remains poorly understood. We aimed to examine the natural history of pathologically confirmed NF-PNET. Methods This single-center retrospective case series investigated NF-PNETs that were pathologically diagnosed using endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) at our hospital between 2014 and 2018. Patients who were followed up without treatment due to their general condition or their wish were included in the study. Patients' background characteristics, imaging findings, pathological findings, and long-term prognoses were investigated using medical records. Results Overall, 26 patients were diagnosed with NF-PNET by EUS-FNA during the observation period. Of these, 9 patients (3 men and 6 women; median age: 64 years old) were followed up without treatment. All of these patients were asymptomatic, and localization was noticed in 3 cases in the head, body, and tail (1 each), with a median size of 12 (range: 4-18) mm. Neuroendocrine tumor (Grade 1 [G1]) was pathologically diagnosed in all patients with EUS-FNA. The median observation period was 63 (range: 26-90) months. Tumor growth and distant metastasis were not observed in any of the nine patients who remained asymptomatic. Conclusion Follow-up is a feasible option for asymptomatic NF-PNET ≤20 mm in size with a pathological grade of G1.

Tumor vascularity on contrast-enhanced computed tomography as a predictive marker of metastatic potential for small nonfunctioning pancreatic neuroendocrine tumors

BackgroundAlthough surgical resection is generally suggested for nonfunctioning pancreatic neuroendocrine tumors, observation can be proposed for carefully selected patients with small tumors. However, the indications for observation remain unclear. MethodsThis retrospective study included 77 patients with nonfunctioning pancreatic neuroendocrine tumors, including small tumors (≤2.0 cm, n = 41), who received pancreatectomy. The ratio of the mean computed tomography value of a tumor in the late arterial/equilibrium phase (computed tomography a/e ratio) was used to evaluate tumor vascularity. Pathologic examinations of small tumors were conducted. The associations among the computed tomography a/e ratio, pathologic findings, and survival outcomes were investigated. ResultsSmall tumors were pathologically categorized by the degree of fibrosis as follows: medullary (n = 20), intermediate (n = 11), and fibrotic (n = 10). The fibrotic type had significantly lower computed tomography a/e ratios than the medullary type (median, 1.42 vs 2.03, P < .001). The median number of vessels with microscopic venous invasion was significantly higher in the fibrotic type than in the medullary type (4.5 vs 0.0, P < .001). The cutoff value of the computed tomography a/e ratio for predicting microscopic venous invasion was determined to be 1.54 by the receiver operating characteristic curve (area under the curve, 0.832; sensitivity, 80.0%; specificity, 83.9%; accuracy, 82.9%). Microscopic venous invasion was an independent prognostic factor for relapse-free survival in overall patients (hazard ratio 5.18, P = .017). ConclusionThe computed tomography a/e ratio may be a useful predictor of the metastatic potential of nonfunctioning pancreatic neuroendocrine tumors and may help decide the indications of observation for small nonfunctioning pancreatic neuroendocrine tumors.

Observational study of surgical resection in small non-functional pancreatic neuroendocrine tumors: AS SEER-based study

The potential benefits of surgical resection for small non-functional pancreatic neuroendocrine tumors (NF-PNETs) in terms of survival remain uncertain. This study aimed to evaluate the impact of surgical treatment on patients with NF-PNETs. Using SEER data, we identified 1102 patients from 2004 to 2015 with well and moderately differentiated pancreatic neuroendocrine tumors (PNETs). The associations between continuous variables and receipt of surgery were assessed using Wilcoxon rank-sum tests. Kaplan–Meier survival curves for OS were compared using the log-rank test. We compared outcomes in patients who received surgical resection with those in patients who did not, using a univariable Cox model with inverse probability weighting according to the propensity score and propensity-score matching. Among the cohort of 1102 patients, a majority of 965 individuals (87%) underwent surgical intervention. Upon conducting univariate analysis, we observed that surgical treatment significantly prolonged patients' survival [HR = 0.41, 95% CI [0.26–0.65] P < 0.001]. However, the old [HR = 3.27, 95% CI (2.24–4.76), P 0.001], male gender [HR = 1.82, 95% CI (1.23–2.68), P = 0.003], and moderately well-differentiated factors [HR = 1.71, 95% CI (1.04–2.80), P = 0.034] were found to potentially decrease patients' survival time. In the multivariate analysis, male gender [HR = 1.73, 95% CI (1.15–2.61), P = 0.009] and the old factor [HR = 3.52, 95% CI (2.33–5.31), P < 0.001] emerged as influential predictors with higher hazard ratios. Notably, surgical treatment remained a significant factor associated with improved overall survival [HR = 0.53, 95% CI (0.33–0.84), P = 0.007]. Propensity-score matching and inverse probability weighting were employed as analytical techniques. The univariate analysis results showed favorable outcomes in the weight group [HR = 0.48, 95% CI (0.29–0.78), P = 0.003] and matched group [HR = 0.44, 95% CI (0.22–0.85), P = 0.015], respectively. Survival analysis further confirmed that surgical treatment contributed to increased overall survival (log rank, P < 0.05) in both the matching and weight groups. Patients diagnosed with small, non-functioning pancreatic neuroendocrine tumors who undergo surgical intervention exhibit improved overall survival (OS) outcomes. Therefore, surgery is strongly recommended for this patient population.

Response to Commentary on '"Long-Term Outcomes of Parenchyma-Sparing and Oncologic Resections in Patients With Nonfunctional Pancreatic Neuroendocrine Tumors

Response to Commentary on '"Long-Term Outcomes of Parenchyma-Sparing and Oncologic Resections in Patients With Nonfunctional Pancreatic Neuroendocrine Tumors <3 cm in a Large Multicenter Cohort".

Evaluation of Survival Following Surgical Resection for Small Nonfunctional Pancreatic Neuroendocrine Tumors

The number of patients with small nonfunctional pancreatic neuroendocrine tumors (NF-PanNETs) is increasing. However, the role of surgery for small NF-PanNETs remains unclear. To evaluate the association between surgical resection for NF-PanNETs measuring 2 cm or smaller and survival. This cohort study used data from the National Cancer Database and included patients with NF-pancreatic neuroendocrine neoplasms who were diagnosed between January 1, 2004, and December 31, 2017. Patients with small NF-PanNETs were divided into 2 groups: group 1a (tumor size, ≤1 cm) and group 1b (tumor size, 1.1-2.0 cm). Patients without information on tumor size, overall survival, and surgical resection were excluded. Data analysis was performed in June 2022. Patients with vs without surgical resection. The primary outcome was overall survival of patients in group 1a or group 1b who underwent surgical resection compared with those who did not, which was evaluated using Kaplan-Meier estimates and multivariable Cox proportional hazards regression models. Interactions between preoperative factors and surgical resection were analyzed with a multivariable Cox proportional hazards regression model. Of the 10 504 patients with localized NF-PanNETs identified, 4641 were analyzed. These patients had a mean (SD) age of 60.5 (12.7) years and included 2338 males (50.4%). The median (IQR) follow-up time was 47.1 (28.2-71.6) months. In total, 1278 patients were in group 1a and 3363 patients were in group 1b. The surgical resection rates were 82.0% in group 1a and 87.0% in group 1b. After adjustment for preoperative factors, surgical resection was associated with longer survival for patients in group 1b (hazard ratio [HR], 0.58; 95% CI, 0.42-0.80; P < .001) but not for patients in group 1a (HR, 0.68; 95% CI, 0.41-1.11; P = .12). In group 1b, interaction analysis found that age of 64 years or younger, absence of comorbidities, treatment at academic institutions, and distal pancreatic tumors were factors associated with increased survival after surgical resection. Findings of this study support an association between surgical resection and increased survival in select patients with NF-PanNETs measuring 1.1 to 2.0 cm who were younger than 65 years, had no comorbidities, received treatment at academic institutions, and had tumors of the distal pancreas. Future investigations of surgical resection for small NF-PanNETs that include the Ki-67 index are warranted to validate these findings.

ASO Visual Abstract: Reappraisal of Malignant Risk Assessment for Small (≤20 mm) Non-functioning Pancreatic Neuroendocrine Tumors.

ASO Visual Abstract: Reappraisal of Malignant Risk Assessment for Small (≤20 mm) Non-functioning Pancreatic Neuroendocrine Tumors.

Comment on: Are Parenchyma-Sparing Resections Really Appropriate for Small (

Comment on: Are Parenchyma-Sparing Resections Really Appropriate for Small (<3 cm) Nonfunctional Pancreatic Neuroendocrine Tumors?

Response to Commentary "Are Parenchyma-Sparing Resections Really Appropriate for Small (

Response to Commentary "Are Parenchyma-Sparing Resections Really Appropriate for Small (<3 cm) Non-Functional Pancreatic Neuroendocrine Tumors?"

Evaluating surgical treatment options for small nonfunctional pancreatic neuroendocrine tumors in the NCDB.

645 Background: The role of surgery for small (≤2 cm), nonfunctional pancreatic neuroendocrine tumors (NF-PNETs) remains controversial due to the wide range of tumor aggressiveness. Consensus guidelines of the US, Europe, and Japan offer different recommendations for treatment of small NF-PNETs. The objective of this study is to evaluate the survival benefit of surgical resection for small NF-PNETs. Methods: Patients with NF-PNETs were identified in the National Cancer Database from 2004 to 2018. Small NF-PNETs were divided into two groups: group 1a (tumor ≤1 cm) and group 1b (tumor 1.1 – 2.0 cm). Cox regression models were used to compare the overall survival between resected and unresected small NF-PNETs patients. Interactions between preoperative factors and surgery were estimated using subgroup analyses. Results: We identified 1,278 patients in group 1a and 3,363 patients in group 1b. After adjusting for preoperative factors, surgery was associated with longer survival for patients in group 1b (HR, 0.58; 95% CI, 0.42–0.80; P &lt;0.001), but not for patients in group 1a (HR, 0.68; 95% CI, 0.41–1.11; P = 0.122). Interaction analysis found that age younger than 65 years, fewer comorbidities, treatment at academic institutions, distal pancreatic tumors, and clinical lymph node metastasis were factors associated with longer survival in group 1b by surgery. Conclusions: Findings from this large study support surgical resection for some patients with NF-PNETs (1.1 – 2.0 cm). This, of course, must be taken in context with the patient’s clinical situation. Based on data available for analysis in this study, resection for subcentimeter NF-PNETs does not appear to be of general benefit, but should also be investigated in the context of Ki-67 index.[Table: see text]

Clinicopathological characteristics, survival outcomes and prognostic factors in the cT1N0M0 pancreatic neuroendocrine tumors: A SEER-based study.

Small nonfunctional pancreatic neuroendocrine tumors ≤2 cm have different biological features, and there is no gold standard treatment for them. This study aimed to assess the risk of malignancy of small non-functional pancreatic neuroendocrine tumors and their outcomes after radical resection. The optimal management of small, incidentally detected pancreatic neuroendocrine tumors is controversial, with the aim of identifying factors predicting survival in patients with clinical stage T1N0M0 (cT1N0M0) pancreatic neuroendocrine tumors and whether surgical treatment improves survival. Using the Surveillance, Epidemiology, and End Results database, we identified 637 patients with cT1N0M0 pancreatic neuroendocrine tumors from 2010 to 2015, including clinicopathological characteristics, treatment modalities, and outcome data. From the surveillance, epidemiology, and end results database of 637 patients with cT1N0M0 PNENs, 564 were treated surgically. Age (P = .000), sex (P < .001), and surgery (P < .001) were independent risk factors affecting survival. Patients who have undergone surgery, women and young adults have a higher overall survival rate. The following independent prognostic predictors for cT1N0M0 pNENs were identified: age, sex, and surgery. At last, we concluded that Surgery can increase the overall survival of pancreatic neuroendocrine tumors in T1N0M0.

A novel tool to predict nodal metastasis in small pancreatic neuroendocrine tumors: A multicenter study

BackgroundNonfunctional pancreatic neuroendocrine tumors display a wide range of biological behavior, and nodal disease is associated with metastatic disease and poorer survival. The aim of this study was to develop a tool to predict nodal disease in patients with small (≤2 cm) nonfunctional pancreatic neuroendocrine tumors. MethodsA multicenter retrospective study was performed on patients undergoing resection for small nonfunctional pancreatic neuroendocrine tumors. Patients with genetic syndromes, metastatic disease at diagnosis, neoadjuvant therapy, or positive resection margin were excluded. Factors associated with nodal disease were identified to develop a predictive model. Internal validation was performed using bootstrap with 1,000 resamples. ResultsNodal disease was observed in 39 (11.1%) of the 353 patients included. Presence of nodal disease was significantly associated with lower 5-year disease-free survival (71.6% vs 96.2%, P < .001). Two predictors were strongly associated with nodal disease: G2 grade (odds ratio: 3.51, 95% confidence interval: 1.71–7.22, P = .001) and tumor size (per mm increase, odds ratio: 1.14, 95% confidence interval: 1.03–1.25, P = .009). Adequate discrimination was observed with an area under the curve of 0.71 (95% confidence interval: 0.63–0.80). Based on risk distribution, 3 risk groups of nodal disease were identified; low (<5%), intermediate (≥5% to <20%), and high (≥20%) risk. The observed mean risk of nodal disease was 3.7% in the low-risk patients, 9.6% in the intermediate-risk patients, and 30.4% in the high-risk patients (P < .001). The 10-year disease-free survival in the low, intermediate, and high-risk groups was 100%, 88.8%, and 50.1%, respectively. ConclusionOur model using tumor grade and size can predict nodal disease in small nonfunctional pancreatic neuroendocrine tumors. Integration of this tool into clinical practice could help guide management of these patients.

Reappraisal of a 2-cm Cutoff Size for the Management of Nonfunctional Pancreatic Neuroendocrine Tumors: A Population-Based Study.

BackgroundExpectant observation and aggressive surgery are both recommended for small nonfunctional pancreatic neuroendocrine tumors (NF-PanNETs). However, the optimal management of small NF-PanNETs remains disputable due to the heterogeneous clinical behavior.MethodsPatients who were diagnosed with pancreatic neuroendocrine neoplasms (PanNENs) between 2000 and 2018 were identified from the surveillance, epidemiology, and end results (SEER) database and reviewed retrospectively. Tumor aggressiveness was defined as poor differentiation, lymph node involvement, liver involvement, and advanced stage. The best cutoff of tumor size associated with tumor aggressiveness was determined through the receiver operating characteristic (ROC) curve analysis. Univariate and multivariate analyses were used to identify prognostic factors in patients with tumors of ≤2 cm.ResultsA total of 5,172 patients with PanNENs were enrolled, including 1,760 (34.0%) tumors ≤2 cm and 3,412 (66.0%) tumors >2 cm. A 2.5-cm cutoff size was found to be associated with a satisfactory ability in predicting tumor aggressiveness. On multivariate analysis, age, gender, ethnicity, tumor grade, tumor number, and stage were independent prognostic factors for overall survival (OS) in patients with tumors less than or equal to 2 cm in size. A total of 1,621 patients were diagnosed with NF-PanNETs according to the WHO classification, of whom 1,350 underwent surgery, 271 performed active observation. The OS was significantly better in the surgery group compared to the observation group regardless of propensity score analysis. Additionally, a total of 407 patients were selected based on the multivariate Cox regression analysis, of whom 46 underwent observation, 361 underwent surgery, and the OS was comparable.ConclusionExpectant observation may be a reasonable alternative to aggressive surgical resection in highly selected small NF-PanNET patients. Also, the decision to observe versus surgery should not only be based on tumor size alone but also take into account other important clinicopathological factors.

Long-term Outcomes of Parenchyma-sparing and Oncologic Resections in Patients With Nonfunctional Pancreatic Neuroendocrine Tumors

The role of parenchyma-sparing resections (PSR) and lymph node dissection in small (<3cm) nonfunctional pancreatic neuroendocrine tumors (PNET) is unlikely to be studied in a prospective randomized clinical trial. By combining data from 4 high-volume pancreatic centers we compared postoperative and long-term outcomes of patients who underwent PSR with patients who underwent oncologic resections. Retrospective review of prospectively collected clinicopathologic data of patients who underwent pancreatectomy between 2000 and 2021 was collected from 4 high-volume institutions. PSR and lymph node-sparing resections (enucleation and central pancreatectomy) were compared to those who underwent oncologic resections with lymphadenectomy (pancreaticoduodenectomy, distal pancreatectomy). Statistical testing was performed using χ 2 test and t test, survival estimates with Kaplan-Meier method and multivariate analysis using Cox proportional hazard model. Of 810 patients with small sporadic nonfunctional PNETs, 121 (14.9%) had enucleations, 100 (12.3%) had central pancreatectomies, and 589 (72.7%) patients underwent oncologic resections. The median age was 59 years and 48.2% were female with a median tumor size of 2.5cm. After case-control matching for tumor size, 221 patients were selected in each group. Patients with PSR were more likely to undergo minimally invasive operations (32.6% vs 13.6%, P <0.001), had less intraoperative blood loss (358 vs 511ml, P <0.001) and had shorter operative times (180 vs 330 minutes, P <0.001) than patients undergoing oncologic resections. While the mean number of lymph nodes harvested was lower for PSR (n=1.4 vs n=9.9, P <0.001), the mean number of positive lymph nodes was equivalent to oncologic resections (n=1.1 vs n=0.9, P =0.808). Although the rate of all postoperative complications was similar for PSR and oncologic resections (38.5% vs 48.2%, P =0.090), it was higher for central pancreatectomies (38.5% vs 56.6%, P =0.003). Long-term median disease-free survival (190.5 vs 195.2 months, P =0.506) and overall survival (197.9 vs 192.6 months, P =0.372) were comparable. Of the 810 patients 136 (16.7%) had no lymph nodes resected. These patients experienced less blood loss, shorter operations ( P <0.001), and lower postoperative complication rates as compared to patients who had lymphadenectomies (39.7% vs 56.9%, P =0.008). Median disease-free survival (197.1 vs 191.9 months, P =0.837) and overall survival (200 vs 195.1 months, P =0.827) were similar for patients with no lymph nodes resected and patients with negative lymph nodes (N0) after lymphadenectomy. In small <3cm nonfunctional PNETs, PSRs and lymph node-sparing resections are associated with lower blood loss, shorter operative times, and lower complication rates when compared to oncologic resections, and have similar long-term oncologic outcomes.

Impact of tumor size and location on endoscopic ultrasound-guided sampling of pancreatic neuroendocrine tumors: A recursive partitioning analysis

BackgroundCurrent guidelines provide weak recommendations to treat small (<2 cm) non-functional pancreatic neuroendocrine tumors with low Ki-67 proliferation index either by resection or clinical follow-up. However, there is a lack of consensus regarding the minimal size of pNET, which allows EUS-guided biopsy with high enough diagnostic accuracy for stratification. MethodsWe conducted a retrospective, bicentric analysis of patients who had undergone EUS-guided pNET sampling in two tertiary care Endoscopy Units in Germany and Poland. Using a recursive partitioning of the tree-aided model, we aimed to stratify the probability of successful EUS-guided biopsy of pNET lesions according to their size and location. ResultsIn our pNET cohort, successful histological confirmation of a pNET diagnosis was achieved in 59/69 (85.5%) cases at the initial EUS-guided biopsy. In 41 patients with a pNET size less than 18.5 mm, the EUS-guided first biopsy was successful in 90.2%. In 16 of these patients with smaller lesions, EUS-guided sampling was 100% in very small (less than 11 mm) and extremely small lesions (less than 8 mm). The biopsy success rate was 100% in tail lesions in the size range between ≥5.95 and <8.1 mm but only 33.3% independent of the investigator in pancreatic head or body, with an error rate of 11.2% ConclusionUsing a recursive partitioning of the tree-aided stratification model, we demonstrate for the first time that in balancing risks and benefits, very small pNETs (<1 cm) in the tail of the pancreas should be sampled under EUS-guidance.

Is non-operative management of small asymptomatic sporadic nonfunctioning pancreatic neuroendocrine tumors safe?

Is non-operative management of small asymptomatic sporadic nonfunctioning pancreatic neuroendocrine tumors safe?

Management of non-functional pancreatic neuroendocrine tumors by endoscopic ultrasound-guided radiofrequency ablation: Retrospective study in two tertiary centers.

Recently, there has been growing interest in investigating endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) for the management of small non-functional pancreatic neuroendocrine tumors (nf pNETs). A bicentric retrospective study was performed that included patients with histologically confirmed nf pNETs who were consecutively treated by EUS-RFA between December 2015 and March 2021 at two tertiary referral centers. In 27 patients (mean age 65.0 years, 52% male), EUS-RFA was successfully performed. All patients had sporadic G1 lesions (mean size 14.0 ± 4.6 mm, 7% uncinated process, 22% head, 11% body, 19% body/tail junction, and 41% tail). Overall, 9/27 lesions (33%) were cystic. The mean hospital stay was 3.2 days. Complete treatment response was confirmed in 25/27 patients (93%) on cross-sectional imaging (mean follow-up 15.7 ± 12.2 months, range 2-41 months). Two patients had two EUS-RFA sessions until complete necrosis was observed. Periprocedural acute pancreatitis occurred in 4/27 (14.8%), three of them were treated by endoscopic cystogastrostomy (11.1%). One patient underwent secondary surgery. The histopathology of the resected specimen revealed 3 mm of residual tumor tissue. EUS-RFA seems to be a promising treatment strategy for the management of small nf pNETs with excellent efficacy. Further evidence focusing on long-term survival, safety profile and recurrence is needed.

National Trends in the Management of Small Localized Non-Functioning Pancreatic Neuroendocrine Tumors

Introduction: Controversy exits regarding the role of resection in small non-functioning pancreatic neuroendocrine tumors (NF-PNETs). Our objective was to characterize national trends in the management of small NF-PNETs and elucidate factors associated with treatment selection and survival. Methods: The 2004-2015 National Cancer Database was queried for patients with small (<2cm, cT1) NF-PNETs and clinically negative nodes (cN0). Patients were stratified by observation versus surgical resection (pancreaticoduodenectomy (WP) or distal pancreatectomy (DP)). Results: Of 2,421 patients, 1,717 (71%) underwent pancreatectomy (DP 69.9%; WP 30.1%). Despite a majority undergoing surgery, rates of pancreatectomy decreased significantly over time, with rates of WP (slope -2.44, p=0.03) decreasing at a greater magnitude than DP (slope -1.40, p=0.04). A significant decrease in pancreatectomy was noted at academic centers (p=0.008), but not non-academic centers (p=0.08). Independent predictors of resection included younger age (OR 0.96; CI 0.95-0.97), private insurance (OR 0.69; CI 0.55-0.87), tumor location within the body/tail (OR 2.0; CI 1.76-2.73), and tumor size 1-2cm (OR 1.81; CI 1.45-2.26). Kaplan Meier analysis demonstrated a survival advantage associated with resection of tumors 1-2cm in size (p<0.001), but not for tumors <1cm (p=0.16). While surgery remained independently prognostic for survival on Cox analysis (HR 2.95; CI 1.87-4.65), tumor size was no longer independently prognostic (p=0.78). Instead, tumor grade represented the single most important prognostic factor for death (HR 5.14; CI 1.83-14.42). Conclusion: Evidence-based guidelines are gradually being implemented across institution types. Tumor grade and other socio-demographic factors, rather than tumor size, appear to be the primary determinants of survival.

The clinicopathologic and operative characteristics of patients with small nonfunctioning pancreatic neuroendocrine tumors.

Incidentally detected, small nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) are increasingly diagnosed on imaging modalities. This retrospective investigation evaluated the clinicopathologic characteristics and perioperative and oncologic outcomes in patients with small NF-PNETs undergoing curative resection. The medical records of 444 patients who underwent pancreatic resection for NF-PNETs at a single, large-volume institution between January 2000 and December 2018 were retrospectively reviewed. Patients were divided into those with small (≤2cm) and large (>2cm) tumors based on the largest tumor diameter on preoperative computed tomography (CT). Outcomes were also evaluated in subgroups of patients with small NF-PNET who did and did not undergo lymphadenectomy. Of the 444 patients with NF-PNETs, 195 (43.9%) had small (≤2cm) and 249 (56.1%) had large (>2cm) NF-PNETs. The rate of parenchyma-preserving surgery (14.4% vs. 7.2%, p=0.014) and the ratio of spleen preservation for left-sided pancreatectomy (65.6% vs. 38.3%, p < 0.001) were higher in the small NF-PNET group. Size on CT >2cm (p < 0.001, hazard ratio [HR]: 5.836, 95% confidence interval [CI]: 2.474-13.769), presence of perineural invasion (p < 0.001, HR: 3.025, 95% CI: 1.640-5.577), World Health Organization (WHO) Grade 2 (p=0.007, HR: 2.861, 95% CI: 1.325-6.176), and WHO Grade 3 (p < 0.001, HR: 11.537, 95% CI: 5.282-25.199) were independent predictors of disease-free survival (DFS). DFS did not differ significantly in patients with small NF-PNETs who did and did not undergo lymphadenectomy (p=0.886). Assessment of long-term oncologic outcomes suggests that surgical resection may cure small NF-PNETs. Minimally invasive surgery and organ-preserving surgery are acceptable treatment options for select patients with small NF-PNETs. The effect on survival outcomes of lymph node dissection for small NF-PNETs remains unclear.

Risk of malignancy and prognosis of sporadic resected small (≤2 cm) nonfunctional pancreatic neuroendocrine tumors.

Small nonfunctional pancreatic neuroendocrine tumors (NF-PNETs) ≤2 cm have variable biological features, and there is no gold standard treatment for their management. The present study aimed to evaluate the risk of malignancy of small NF-PNETs and their outcomes following curative resection. Patients with NF-PNETs undergoing surgical resection at the First Affiliated Hospital, College of Medicine, Zhejiang University, between 2012 and 2017 were included. Clinicopathological characteristics, perioperative results, and prognosis were retrospectively analyzed. A total of 73 patients were identified, including 28 with small NF-PNETs and 45 large PNETs; 32.1% of NF-PNETs ≤2 cm underwent a parenchyma-sparing pancreas surgery, which was >6.7% in large NF-PNETs. No statistically significant differences in perioperative results, postoperative complications, and long-term outcomes were found between small tumors undergoing standard and parenchyma-sparing pancreatectomy. Eighteen small tumors (64.3%) developed a perioperative complication, with a clinically significant pancreatic fistula rate of 25%; however, only 2 patient needed reintervention. Small NF-PNETs in 3 patients were malignant. Multivariate logistic regression showed that grade ≥3 and lymphovascular invasion were independently related to malignancy in NF-PNETs. Small NF-PNETs (≤2 cm) are not immune from potential malignancy. Surgical resection may be considered for small tumors and can provide favorable postoperative and long-term outcomes. Parenchyma-sparing pancreatectomy may be an alternative surgery for selected small local NF-PNETs.

Systematic Review and Metaanalysis of Lymph Node Metastases of Resected Pancreatic Neuroendocrine Tumors.

The optimal surgical strategy for pancreatic neuroendocrine tumors (PNETs) is unknown. However, current guidelines recommend a watch-and-wait strategy for small nonfunctional PNETs (NF-PNETs). The aim of this study is to investigate the risk stratification and prognostic significance of lymph node metastasis (LNM) of PNETs to guide decision-making for lymphadenectomy. The MEDLINE and Web of Science databases were systematically searched for studies reporting either risk factors of LNM in resected PNETs or survival of patients with LNM. The weighted average incidence of LNM was calculated according to tumor characteristics. Random-effects metaanalyses were performed, and pooled hazard ratios (HR) and their 95% confidence intervals (CI) were calculated to determine the impact of LNM on overall survival (OS). In subgroup analyses, NF-PNETs were assessed. From a total of 5883 articles, 98 retrospective studies with 13,374 patients undergoing resection for PNET were included. In all PNETs, the weighted median rates of LNM were 11.5% for small (≤ 2cm) PNETs and 15.8% for G1 PNETs. In NF-PNETs, the rates were 11.2% for small PNETs and 10.3% for G1 PNETs. LNM of all PNETs (HR 3.87, 95% CI 3.00-4.99, P < 0.001) and NF-PNETs (HR 4.98, 95% CI 2.81-8.83, P < 0.001) was associated with worse OS. LNM is potentially prevalent even in small and well-differentiated PNETs and is associated with worse prognosis. A watch-and-wait strategy for small NF-PNETs should be reappraised, and oncologic resection with lymphadenectomy can be considered. Prospective and controlled studies are needed in the future.