Small Pancreatic Neuroendocrine Tumors Research Articles

Endoscopic ultrasound‐guided tissue acquisition allows a reliable proliferation assessment of small (≤20 mm) pancreatic neuroendocrine tumors

Endoscopic ultrasound‐guided tissue acquisition allows a reliable proliferation assessment of small (≤20 mm) pancreatic neuroendocrine tumors

Radiomics machine learning algorithm facilitates detection of small pancreatic neuroendocrine tumors on CT

PurposeThe purpose of this study was to develop a radiomics-based algorithm to identify small pancreatic neuroendocrine tumors (PanNETs) on CT and evaluate its robustness across manual and automated segmentations, exploring the feasibility of automated screening. Materials and methodsPatients with pathologically confirmed T1 stage PanNETs and healthy controls undergoing dual-phase CT imaging were retrospectively identified. Manual segmentation of pancreas and tumors was performed, then automated pancreatic segmentations were generated using a pretrained neural network. A total of 1223 radiomics features were independently extracted from both segmentation volumes, in the arterial and venous phases separately. Ten final features were selected to train classifiers to identify PanNETs and controls. The cohort was divided into training and testing sets, and performance of classifiers was assessed using area under the receiver operator characteristic curve (AUC), specificity and sensitivity, and compared against two radiologists blinded to the diagnoses. ResultsA total of 135 patients with 142 PanNETs, and 135 healthy controls were included. There were 168 women and 102 men, with a mean age of 55.4 ± 11.6 (standard deviation) years (range: 20–85 years). Median PanNET size was 1.3 cm (Q1, 1.0; Q3, 1.5; range: 0.5–1.9). The arterial phase LightGBM model achieved the best performance in the test set, with 90 % sensitivity (95 % confidence interval [CI]: 80–98), 76 % specificity (95 % CI: 62–88) and an AUC of 0.87 (95 % CI: 0.79–0.94). Using features from the automated segmentations, this model achieved an AUC of 0.86 (95 % CI: 0.79–0.93). In comparison, the two radiologists achieved a mean 50 % sensitivity and 100 % specificity using arterial phase CT images. ConclusionRadiomics features identify small PanNETs, with stable performance when extracted using automated segmentations. These models demonstrate high sensitivity, complementing the high specificity of radiologists, and could serve as opportunistic screeners.

Prospective study on stereotactic body radiotherapy for small pancreatic neuroendocrine tumors: tolerance and effectiveness analysis.

Surgery is the standard treatment for pancreatic neuroendocrine tumors (pNETs), obtaining favorable results but associating high morbidity and mortality rates. This study assesses stereotactic body radiation therapy (SBRT) as a radical approach for small (< 2cm) nonfunctioning pNETs. From January 2017 to June 2023, 20 patients with small pNETs underwent SBRT in an IRB-approved study. Endpoints included local control, tolerance, progression-free survival, and overall survival (OS). Diagnostic assessments comprised endoscopy, CT scans, OctreScan or PET-Dotatoc, abdominal MRI, and histological confirmatory samples. In a 30-month follow-up of 20 patients (median age 55.5years), SBRT was well-tolerated with no grade > 2 toxicity. 40% showed morphological response, 55% remained stable. Metabolically, 50% achieved significant improvement. With a median OS of 41.5months, all patients were alive without local or distant progression or need for surgical resection. SBRT is a feasible and well-tolerated approach for small neuroendocrine pancreatic tumors, demonstrating effective local control. Further investigations are vital for validation and extension of these findings.

Endoscopic loco-regional treatment in controlling pancreatic neuroendocrine tumors (PNETs) behavior: a case series and literature review.

Pancreatic neuroendocrine tumors (PNETs) are considered rare pancreatic neoplasms, and it is a challenging disease entity due to its indolent behavior and is difficult to manage. Diagnostic challenge is usually found in the imaging-based approach, such as transabdominal ultrasound, abdominal CT scan, and abdominal MRI. Surgery is still the main key player in controlling the disease. The main problems in clinical practice are the early detection of small PNETs lesion and non-functional PNET (NF-PNET) cases. Most cases usually come with large tumor size or metastatic disease. Endoscopic ultrasound (EUS) has been well-known as the most sensitive tool for early detection of pancreatic malignancy. It has now also been developed for managing pancreatic cancer, such as tumor ablation therapy. We presented four variety of PNETs cases (one patient with non-functioning PNETs and three patients with functioning PNETs) who have been successfully treated with EUS-guided radiofrequency ablation (RFA) with good control of tumor growth during follow-up. One patient with a large-size insulinoma could have the tumor controlled gradually after several EUS-RFA sessions. No adverse events or major complications were observed during and after the EUS-RFA procedure. EUS has been shown as a promising tool not only for more accurate diagnosis but also for tumor growth control. However, it would need further comparison studies between EUS and surgical approaches to make a better treatment strategy.

HPB P28 Continuous glucose monitoring improves the diagnosis of insulinoma and surveillance after endoscopic ablation therapy

Abstract Background Insulinomas are the most common functioning pancreatic neuroendocrine tumours (PNET) and are classically diagnosed according to Whipple’s triad. The gold-standard diagnostic test (72 hour fasting glucose/C-peptide) is difficult for patients, and risks mis-diagnosing patients who only experience post-prandial symptoms. Moreover, the advent of endoscopic ablative techniques means that confirming successful treatment can be challenging when compared with surgical resection. This study aimed to investigate the value of continuous glucose monitoring (CGM) to: a) confirm the diagnosis of insulinoma; b) guide symptom management whilst awaiting definitive treatment; and c) as a surveillance tool in patients electing for non-surgical interventions. Methods A 61-year-old healthy male presented with post-prandial sweating, vacant episodes and reduced exercise tolerance which resolved upon consuming glucose. Computed Tomography demonstrated a 2cm exophytic hypervascular lesion in the pancreatic body, consistent with a NET, and correlated with an Octreotide avid lesion upon SPECT/CT. Overnight fasting glucose/c-peptide was not confirmatory. The target glucose range was defined as 4.0-9.9 mmol/L and critical hypoglycaemia as ≤2.9mmol/L. Data from CGM were analysed (Time in range and critical hypoglycaemia [Chi2]; glycaemic control and glycaemic variability [T-test]) during diagnosis, in the first week post-ablation, and the recovery phase beyond 3 weeks. Results Data from 22,008 glucose levels were analysed over a 90 day period. Time in range during diagnosis was 67.25%, 82.8% (p&amp;lt;0.0001) post-ablation, and 98.9% (P&amp;lt;0.0001) during recovery. Critical hypoglycaemia occurred in 5.2% of measurements during diagnosis, 1.9% (p&amp;lt;0.0001) post-ablation, and 0.1% (p&amp;lt;0.0001) during recovery. Glucose levels (mean [SD] mmol/L) were 4.4 (0.47) during diagnosis, 4.9 (0.29) (p=0.0001) post-ablation, and 5.7 (0.42) (p&amp;lt;0.0001) during recovery. Glycaemic variability (mean [SD] %CV) was 19.4 (5.09) during diagnosis, 20.17 (5.60) post-ablation (p=0.630), and 11.3 (5.53) (p&amp;lt;0.0001) during recovery. Temporal changes identifying post-prandial hypoglycaemia during diagnosis, and resolution during recovery, are illustrated (Figure 1). Conclusions CGM has utility to accurately diagnose insulinoma when standard tests are negative, and to improve quality of life by alerting patients to life-threatening critical hypoglycaemia. As parenchymal preserving non-operative therapies increase in popularity, especially for patients with small PNETs, sensitive, reliable, and acceptable surveillance techniques are required in order to confirm treatment success and monitor for recurrence. Proactive engagement with commissioning and regulatory bodies is necessary in order to harness the potential from emerging technologies, so that PNET patients can benefit in a similar manner as those with type 1 Diabetes Mellitus.

Approaching Small Neuroendocrine Tumors with Radiofrequency Ablation.

In recent years, small pancreatic neuroendocrine tumors (pNETs) have shown a dramatic increase in terms of incidence and prevalence, and endoscopic ultrasound (EUS) radiofrequency ablation (RFA) is one potential method to treat the disease in selected patients. As well as the heterogeneity of pNET histology, the studies reported in the literature on EUS-RFA procedures for pNETs are heterogeneous in terms of ablation settings (particularly ablation powers), radiological controls, and radiological indications. The aim of this review is to report the current reported experience in EUS-RFA of small pNETs to help formulate the procedure indications and ablation settings. Another aim is to evaluate the timing and the modality of the radiological surveillance after the ablation. Moreover, new studies on large-scale series are needed in terms of the safety and long-term oncological efficacy of RFA on these small lesions.

Characteristics of small pancreatic neuroendocrine tumors and risk factors for invasion and metastasis.

The number of people with small pancreatic neuroendocrine tumors (pNETs) (tumors with a diameter less than or equal to 2cm) is gradually increasing, but the selection of treatment strategy is still controversial. Our aim was to characterize small pNETs with a poor prognosis and to define the impact of aggressive small pNETs on survival and the risk factors for the development of invasive disease. Patients with pNETs diagnosed between 2004 and 2019 and a tumor diameter of 2cm or less were selected from the SEER Registry. Kaplan-Meier survival analysis was used to identify the factors affecting patient survival, and binary logistic regression was used to identify the associated risk factors. A total of 3261 patients with pNETs were enrolled in the study. Both older and younger patients benefited from surgery. Regional invasion occurred in 10% of the patients, and distant metastases occurred in 9% of the patients, but in both categories, those who underwent surgery had better survival outcomes than those who did not. There was no difference in survival between patients with a tumor diameter of 1-2 cm and those with a tumor diameter of less than 1cm, and there was no difference in survival between patients with functional and nonfunctional small pNETs. However, the survival of patients with pNETs in the head of the pancreas was worse than that of patients with tumors in other parts of the pancreas. Survival was worse in elderly patients and in those with poorly differentiated and undifferentiated tumors. Lymphatic metastasis, regional invasion, and distant metastasis all worsened the prognosis of patients. The presence or absence of neuroendocrine function, the degree of tumor differentiation, and the location of the tumor were associated with the risk of lymphatic metastasis and regional invasion; the risk factors for distant metastasis were associated with the degree of differentiation and tumor location. The pNETs ≤ 2cm in diameter could be still aggressive, and patient prognosis worsens after invasive disease develops. Attention to the characteristics of aggressive tumors can improve patient survival.

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?

Small pancreas neuroendocrine tumors: How small is small?

Objective: The current study aimed to investigate the issues in contemporary management strategies that focus on small pancreatic neuroendocrine tumors (PNETs). Data Sources and Study Selection: We searched various scientific databases using specific keywords. Results: Surveillance-only strategies were considered for selected patients. The exact cut-off value of small neuroendocrine tumors for surveillance-only strategies needs to be verified with additional high-level evidence. Conclusion: There is no consensus on the size and treatment strategy for small PNETs currently. Patients with small nonfunctioning PNETs require individualized recommendations for surgery versus active surveillance based on tumor size, radiographic characteristics, and patient characteristics, such as age and comorbidities and also patient references.

Comparison of EUS-guided ablation and surgical resection for nonfunctioning small pancreatic neuroendocrine tumors: a propensity score–matching study

Treatment strategies for small pancreatic neuroendocrine tumors (PNETs)<2 cm in size are still under debate. The feasibility and safety of EUS-guided ethanol ablation (EUS-EA) have been demonstrated. However, sample sizes in previous studies were small with no comparative studies on surgery. Therefore, we aimed to compare the safety and long-term outcomes of EUS-EA with those of surgery for the management of nonfunctioning small PNETs. We retrospectively reviewed patients with PNETs who were managed by EUS-EA (from 2011 to 2018) and surgery (from 2000 to 2018) at Asan Medical Center. Propensity score matching (PSM) was performed to increase comparability. The primary outcome was early and late major adverse events (Clavien-Dindo grade≥III) after treatment. Secondary outcomes were 10-year overall (OS) and disease-specific survival (DSS) rates, length of hospital stay, and development of endocrine pancreatic insufficiency. Of all patients, 97 and 188 patients were included in the EUS-EA and surgery groups, respectively. PSM created 89 matched pairs. EUS-EA was associated with a significantly lower rate of early major adverse events (0% vs 11.2%, P= .003). Late major adverse events occurred more frequently after surgery, with no significant difference between groups (3.4% vs 10.1%, P= .07). Both treatment modalities showed comparable 10-year OS and DSS rates. The length of hospital stay was significantly shorter in the EUS-EA group (4 days vs 14.1 days, P< .001), and endocrine pancreatic insufficiency was less common after EUS-EA than after surgery (33.3% vs 48.6%, P= .121). EUS-EA had fewer adverse events and a shorter hospital stay with similar OS and DSS rates compared with surgery, suggesting that EUS-EA may be a preferred alternative to surgical resection in selected patients with nonfunctioning small PNETs.

Comment on: Survival after active surveillance versus upfront surgery for incidental small pancreatic neuroendocrine tumours.

Comment on: Survival after active surveillance versus upfront surgery for incidental small pancreatic neuroendocrine tumours.

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.

Endoscopic ultrasound-guided radiofrequency ablation of premalignant pancreatic-cystic neoplasms and neuroendocrine tumors: prospective study.

Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is a developing therapeutic approach for premalignant pancreatic-cystic neoplasms (PCNs) and small pancreatic neuroendocrine tumors (PNETs). The safety and efficacy of pancreatic EUS-RFA were previously reported in small series. Herein we report our initial experience with RFA of PCNs and small PNETs. This is a prospective single-center study including 12 patients with a median follow-up of 7 months, with either PCN or PNET &amp;lt;2 cm. Eligible PCNs were either intraductal papillary mucinous neoplasms (IPMN) with worrisome features or mucinous cystic neoplasms (MCN) that were not eligible or refused surgery. Ablation was performed using a 19-gauge dedicated needle. Twelve patients were treated, five had PCNs (four IPMNs, one MCN; median size of 36 mm, range 12-60) and seven had PNETs (median size 8.9 mm, range 6-18). Among patients with PCNs, the complete radiologic response was achieved in 3/5 (60%), partial response in 1/5 (20%) and failure in 1/5 (20%). Among six patients with nonfunctioning PNETs, the complete radiologic response was achieved in 4/6 (66.7%), partial radiologic response in 0/6 (0%) and failure in 2/6 (33.3%). Following a median follow-up of 7 months. One patient with insulinoma showed complete resolution of hypoglycemia-related symptoms. Three postprocedural adverse events occurred, including one case (1/12, 8.3%) of mild acute pancreatitis and two cases (2/12, 16.7%) of abdominal pain. EUS-guided RFA for premalignant PCNs and PNETs is feasible and well-tolerated. Efficacy would be further evaluated with continued follow-up of patients.

Invited Commentary: Minimally Invasive Pancreatectomy for Small Pancreatic Neuroendocrine Tumors: Not How, but Who?

Invited Commentary: Minimally Invasive Pancreatectomy for Small Pancreatic Neuroendocrine Tumors: Not How, but Who?

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?

Are We Undertreating Black Patients with Nonfunctional Pancreatic Neuroendocrine Tumors? Critical Analysis of Current Surveillance Guidelines by Race.

Pancreatic neuroendocrine tumor (PNET) survival outcomes differ by race. Current recommendations for surveillance of PNETs less than 2 cm in size are based on low malignant potential and low rates of lymph node metastases (LNM). We investigated whether these guidelines are universally applicable regardless of race. A multi-institutional analysis of patients with resected, nonfunctional, sporadic PNETs was performed initially using the US Neuroendocrine Study Group dataset with the National Cancer Database as a validation dataset. Patients with distant metastatic disease were excluded from analysis. A total of 453 (388 White and 65 Black) and 5,532 patients (4,772 White and 760 Black) were analyzed in the initial and validation datasets, respectively. White patients had a low incidence of LNM in tumors of less than 2 cm in both datasets (5% and 12%, respectively), which increased with tumor size. However, the incidence of LNM in Black patients was similar in the initial and validation datasets for tumors sized less than 2 cm (23% and 21%) and 2 to 3 cm (21% and 29%). Black patients had a significantly higher incidence of LNM in tumors less than 2 cm in size in the initial and validation datasets (p < 0.01) compared with White patients. The current recommendation for surveillance of PNETs of less than 2 cm in size is likely based on a low rate of LNM seen in a predominantly White population. The incidence of LNM in Black patients with tumors less than 2 cm in size is clinically relevant and concerning. Current guidelines may not be universally applicable, and a more aggressive approach to resection in Black patients with small PNETs may be warranted.

The role of oncologic resection and enucleation for small pancreatic neuroendocrine tumors

BackgroundSurgical management of small pancreatic neuroendocrine tumors (PNETs) is variable. Patients may undergo formal oncologic resection, encompassing regional lymphadenectomy, or enucleation. This study's aim was to understand if enucleation is adequate treatment for PNETs <2 cm MethodsThe US National Cancer Database (NCDB) from 2004 to 2016 was used to identify patients who underwent oncologic resection or enucleation for PNETs <2 cm. Fisher's exact test, log-rank, and logistic regression were used. ResultsOf 4083 patients, 75.6% underwent oncologic resection with a median (range) number of 8 (0–99) lymph nodes examined, and 24.1% underwent enucleation. Five-year overall survival rate was 89.7% in node-negative patients versus 82.1% in node-positive patients (p < 0.001). No survival difference existed between patients who underwent enucleation versus oncologic resection (5-yr OS of 88.5% vs 88.2%, p = 0.064). According to AJCC classification, 3776 patients were clinically-staged with evidence of node-negative disease. Of these, 75.1% underwent oncologic resection, of which 9.9% had node-positive disease after resection. Tumor grade and size independently predicted nodal upstaging after oncologic resection. ConclusionOne-tenth of patients with clinically node-negative disease were node-positive after surgery. Although this was not reflected in overall survival, patients who receive enucleation with higher grade and larger size may benefit from enhanced surveillance for locoregional recurrence.

Clinical Prognosticators of Metastatic Potential in Patients with Small Pancreatic Neuroendocrine Tumors

BackgroundWhile observation of T1(≤2cm) nonfunctioning pancreatic neuroendocrine tumors (NF-PanNETs) is an accepted practice, an ill-defined subgroup of patients with T1 tumors develops metastases. This study aimed to identify those patients via clinical factors. MethodsPatients from the Surveillance, Epidemiology, and End Results (SEER) registry who were diagnosed with NF-PanNET with size ≤2cm between 1998 and 2014 and who underwent primary tumor resection were identified. Binary logistic regression analyses were performed to evaluate factors associated with pathological nodal and systemic metastatic disease. ResultsA total of 612 patients with T1 NF-PanNETs were identified. Of those, 72 (11.7%) developed nodal metastasis and 35 (5.7%) distant metastasis (M1). In the multivariable analysis, tumor location in the pancreatic body (OR 1.903, p=0.03) (OR 1.407, p=0.038) or tail (OR 1.258, p=0.04) (OR 1.612, p=0.021); tumor grade III–IV (OR 2.042, p=0.022) (OR 5.379, p≤0.001); and younger age (OR 0.963, p=0.01) (OR 0.919, p=0.009) were associated with nodal metastases and the presence of M1 disease, respectively. ConclusionWhile the low metastatic potential of ≤2cm NF-PanNET implies watchful waiting to be an appropriate strategy for most patients, the increased risk of metastatic disease in younger patients with high grade (III–IV) body/tail tumors suggests individualized risk stratification to be optimal.

Small pancreatic neuroendocrine tumors: observing and monitoring or prompt surgical resection.

Over recent decades there has been a significant increase in the annual incidence of neuroendocrine tumors of the pancreas (PanNETs), from 0.4 to 0.8 per 100,000 inhabitants, due to a more widespread use of more sensitive imaging techniques (cross-sectional and functional imaging).

A single-center experience in observation of small pancreatic neuroendocrine tumors: to operate or not to operate?

Presenter: Ariana Naaseh BA | University of California, Irvine Background: Pancreatic neuroendocrine tumors (pNET), particularly non-functioning, have gained recent attention due to their malignant transformation potential. The 2019 National Comprehensive Cancer Network (NCCN) Guidelines state optimal management of larger, invasive, or node positive pNET is surgical resection. For small (less than or equal to 2 cm) primary non-metastatic non-functioning pNET observation is recommended in select cases, usually when the tumor is low grade and < 1 cm in size. Decisions to proceed with surveillance versus resection include both consideration of surgical risk and patient co-morbidities as either distal pancreatectomy with or without splenectomy or pancreatoduodenectomy are not without complications. Our study aims to assess whether conservative, non-operative management of small, low-grade non-functioning pNETs is appropriate. Methods: A retrospective review of all patients with a diagnosis of pNET since 2004 referred to our high-volume multidisciplinary hepato-pancreato-biliary center was conducted. Patients with pNET were identified from pre-existing institutional hepato-biliary service database and confirmed via chart review of consultations and follow-up visits, radiologic imaging, and pathology reports. Results: 126 patients were found to have the diagnosis of biopsy-proven pNET. 8 patients were found to have metastatic disease at time of presentation and were excluded from further analysis. Of the 118 patients analyzed, 26 (22.0%) had functioning lesions and 92 (77.9%) non-functioning lesions. All 26 patients with biopsy-proven functioning lesions underwent surgical resection. Of 92 biopsy-proven non-functioning lesions, 36 had lesions less than or equal to 2.0 cm. Of these 36 patients, 31 were observed and 5 underwent an attempt at surgical resection. All 5 operative patients had biopsy-proven Grade 3 lesions. Two of the 5 operative patients were found to have intra-operative metastasis not detected on pre-operative imaging and subsequent resection procedure was aborted. Of the 31 observed patients, 20 (64.5%) were Grade 1 and 11 (35.5%) Grade 2. 10 of the 31 patients (32.2%) had tumor size < 1 cm. The mean follow-up time in months for patients who were observed with lesions less than or equal to 2.0 cm is 27.24 months. Of 31 patients, 24 presented with consistently stable disease on follow up imaging, 7 presented with decreased disease burden (defined as reduction in size or complete absence) and none presented with disease expansion. Of the 7 patients with decreased disease, 5/7 (71.4%) presented with no evidence of pancreatic disease on imaging, despite previous biopsy proven and radiographic proven evidence of disease. Three patients observed with lesions less than or equal to 2 cm died during follow-up, however mortality was not secondary to pNET progression or malignancy. No patients in the non-operative group underwent surgical resection at any time during the follow-up surveillance period. Conclusion: Our retrospective study demonstrates that observation is appropriate for low grade pNET tumors < 1cm, consistent with NCCN guidelines. Additionally, we demonstrate that close observation rather than surgical resection can be considered for non-functioning grade 1 or 2 pNET tumors less than or equal to 2cm, while grade 3 lesions should proceed with surgical resection. Further study is needed to guide standardized management recommendations.