Nonfunctioning Pancreatic Neuroendocrine Tumors Research Articles

Tumeurs neuroendocrines digestives bien différenciées: focus sur les tumeurs pancréatiques

Pancreatic neuroendocrine tumors are rare tumors showing a rising incidence. They are well-differentiated tumors, classified by grade according to their Ki67 index value (grade 1 to 3). Pancreatic neuroendocrine tumors are mainly sporadic tumors but about 10% arise within endocrine tumor syndromes such as multiple endocrine neoplasia type 1. They can be responsible for functional syndromes or non-specific clinical symptoms depending on tumor extension. However, there is also an increase of incidental diagnoses of nonfunctional pancreatic neuroendocrine tumors with the widespread use of high-quality imaging techniques. About 50% of pancreatic neuroendocrine tumors are diagnosed at a metastatic stage, with metastases often located in the liver. Chromogranin A, CT-scan and often an abdominal MRI, and functional imaging should be performed for tumor staging and follow-up. Imaging with PET/CT with68Ga-labeled somatostatin analogues has the highest sensitivity for the diagnosis of pancreatic neuroendocrine tumors, while 18fluorodeoxyglucose PET/CT can sometimes be useful. Overall, they are rather indolent tumors with prolonged survival. Surgery is the recommended treatment in the localized setting, with the exception of small<2cm nonfunctional tumors that can be monitored with imaging techniques. For advanced tumors, there are several available treatments such as somatostatine analogues, chemotherapy, targeted therapies (sunitinib, everolimus), locoregional ablative therapies and Peptide Receptor Radiolabelled Therapy. The treatment strategy will depend on the initial tumor staging, tumor grade, aggressiveness and patient's choice.

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.

Characteristics of malignant tumors of digestive system and autoimmune diseases.

With the development of preoperative examination technology, endoscopic ultrasonography-guided fine-needle aspiration biopsy (EUS-FNA) has been widely used in preoperative pathological diagnosis. However, challenges remain in obtaining appropriate tissue samples and obtaining accurate pathological results to predict disease risk. Therefore, this study aimed to analyze the characteristics of digestive system malignancies and their autoimmune diseases, and to analyze the clinicopathological features, preoperative CT imaging features and pathological grades of pNENs of different pathological degrees of pNENs on the prognosis of pNENs. Experimental results showed that non-functioning pancreatic neuroendocrine tumors showed prominent surrounding hypervascular lesions on multiphase CT examination. Among them, arterial phase and portal venous phase were most clearly imaged at the end, and the degree of local vascular invasion could be used as an index to evaluate its resectability. The sensitivity of CT examination was 63% to 82%, and the specificity was 83% to 100%, depending on the size.

Preoperative acute pancreatitis and hyperenzymemia are associated with poor prognosis in patients with nonfunctional pancreatic neuroendocrine tumors.

We aimed to investigate the prevalence of acute pancreatitis (AP) and hyperenzymemia as well as their clinical impact on postoperative survival outcomes in patients with pancreatic neuroendocrine tumors (PNETs). A retrospective cohort study of 218 patients who underwent radical surgical resection for nonfunctional PNETs (NF-PNETs) was conducted. Multivariate survival analysis was performed by the Cox proportional hazard model, with results expressed as hazard ratio (HR) and 95% confidence interval (CI). Of the 151 patients who met the inclusion criteria, the incidences of preoperative AP and hyperenzymemia were 7.9% (12/152) and 23.2% (35/151), respectively. The mean recurrence-free survival (RFS, 95% CI) for patients in control, AP, and hyperenzymemia groups was 136 (127-144), 88 (74-103), and 90 (61-122) months, with a 5-year RFS rate of 86.5%, 58.3%, and 68.9%, respectively. In the multivariable-adjusted Cox hazard model that included tumor grade and lymph node status, the adjusted HR of AP and hyperenzymemia for recurrence was 2.58 (95% CI: 1.47-7.86, p = 0.008) and 2.43 (95% CI: 1.08-7.06, p = 0.040). Preoperative AP and hyperenzymemia are associated with poor RFS following radical surgical resection in NF-PNETs patients.

Care at high‐volume centers is associated with improved outcomes for patients with pancreatic neuroendocrine tumors: A population‐level analysis

Primary resection and debulking of liver metastases have been associated with improved survival in pancreatic neuroendocrine tumors (PNETs). The treatment patterns and outcomes differences between low-volume (LV) institutions and high-volume (HV) institutions remains unstudied. A statewide cancer registry was queried for patients with nonfunctional PNET from 1997 to 2018. LVinstitutions were defined as treating <5 newly diagnosed patients with PNET per year, while HV institutions treated ≥5. We identified 647 patients: 393 with locoregional (n = 236 HV care, n = 157 LV care) and 254 with metastatic disease (n = 116 HV care, n = 138 LV care). Patients with HV care had improved disease-specific survival(DSS) compared to patients with LV care for both locoregional (median 63 vs. 32 months, p < 0.001) and metastatic disease (median 25 vs. 12 months, p < 0.001). In patients with metastatic disease, primary resection (hazard ratio [HR]: 0.55, p = 0.003) and HV institution (HR: 0.63, p = 0.002) were independently associated with improved DSS. Furthermore, diagnosis at a HV center was independently associated with higher odds of receiving primary site surgery (odds ratio [OR]: 2.59, p = 0.01) and metastasectomy (OR: 2.51, p = 0.03). Care at HV centers is associated with improved DSS in PNET. We recommend referral of all patients with PNETs to HV centers.

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?"

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

Comment on "Long-term Outcomes of Parenchyma-sparing and Oncologic Resections in Patients With Nonfunctional Pancreatic Neuroendocrine Tumors <3 cm in a Large Multicenter Cohort".

Clinical Prediction Models for Recurrence in Patients with Resectable Grade 1 and 2 Sporadic Non-Functional Pancreatic Neuroendocrine Tumors: A Systematic Review.

Recurrence after resection in patients with non-functional pancreatic neuroendocrine tumors (NF-pNET) has a considerable impact on overall survival. Accurate risk stratification will tailor optimal follow-up strategies. This systematic review assessed available prediction models, including their quality. This systematic review followed PRISMA and CHARMS guidelines. PubMed, Embase, and the Cochrane Library were searched up to December 2022 for studies that developed, updated, or validated prediction models for recurrence in resectable grade 1 or 2 NF-pNET. Studies were critically appraised. After screening 1883 studies, 14 studies with 3583 patients were included: 13 original prediction models and 1 prediction model validation. Four models were developed for preoperative and nine for postoperative use. Six models were presented as scoring systems, five as nomograms, and two as staging systems. The c statistic ranged from 0.67 to 0.94. The most frequently included predictors were tumor grade, tumor size, and lymph node positivity. Critical appraisal deemed all development studies as having a high risk of bias and the validation study as having a low risk of bias. This systematic review identified 13 prediction models for recurrence in resectable NF-pNET with external validations for 3 of them. External validation of prediction models improves their reliability and stimulates use in daily practice.

Long-term results after parenchyma-sparing vs. oncologic resection of nonfunctional pancreatic neuroendocrine neoplasms < 3 cm

Long-term results after parenchyma-sparing vs. oncologic resection of nonfunctional pancreatic neuroendocrine neoplasms < 3 cm

Prognostic Significance and Predictors of Nodal Recurrence After Surgery for Non-Functioning Pancreatic Neuroendocrine Tumors.

The prognosis of nodal recurrence after surgery for non-functioning pancreatic neuroendocrine tumors (NF-PanNETs) and its predictors have been poorly investigated. This study aimed to compare clinicopathologic features and survival between patients with nodal relapse and those with distant relapse and to identify predictors of nodal relapse after surgery for NF-PanNETs. All patients (n = 321) submitted to surgery for NF-PanNETs were included. Nodal recurrence was defined as the presence of one or more enlarged LNs at high-quality radiologic examinations and always confirmed by 68Ga-DOTA-PET or biopsy. Altogether, 21 patients (6 %) experienced nodal (± distant) relapse, and 35 patients (11 %) had distant recurrence alone. Isolated nodal recurrence occurred for 23 % of patients with recurrence. Overall, 11 patients died of disease, one of whom (pT3N1G3) had an isolated nodal relapse. The rate of LN metastases (81 % vs 54 %; p = 0.044) and median number of positive LNs (PLN) (3 vs 0; p = 0.019) both were significantly higher for the patients with nodal (± distant)relapse than for those with distant relapse alone. Microvascular invasion (p = 0.046), T stage (p = 0.004), N stage (N1 [p = 0.049]; N2 [p = 0.001]), M stage (p < 0.001), and necrosis (p = 0.011) independently predicted nodal relapse. After distal pancreatectomy (n = 182), 13 patients experienced nodal recurrence, 9 of whom had leftparaortic LNsinvolvement. Lymph nodes are not rare sites of recurrence after surgery for NF-PanNETs. Lymph node involvement is a powerful determinant of nodal relapse. Nodal relapse frequently involves LNs that are not removed during standard lymphadenectomy.

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]

Prognostic Significance of Nodal Micrometastases in Patients with Non-functioning Pancreatic Neuroendocrine Tumors (NF-PanNETs)

Prognostic Significance of Nodal Micrometastases in Patients with Non-functioning Pancreatic Neuroendocrine Tumors (NF-PanNETs)

Pancreaticoduodenectomy in 11-year-old male with a non-functional pancreatic neuroendocrine tumor

Pancreatic neuroendocrine tumors (pNETs) are rare pancreatic neoplasms and are even more uncommon in the pediatric patients, thus leading to a lack of clinical research on diagnosis and management in this population. The purpose of this report is to review relevant literature and discuss a rare occurrence of a non-functioning pNET in a pediatric patient. This is a report of an 11-year-old male who presented with symptomatic anemia and was found to have a 6 cm mass near the pancreatic head with erosion into the duodenum. Surgical biopsy demonstrated a non-functioning pNET. He was successfully managed with complete surgical resection via a standard pancreaticoduodenectomy without evidence of recurrence after 1 year follow up. Further multi-institutional prospective studies or meta-analyses are warranted to further explore optimal management in the pediatric population.

Outcome of nonfunctioning pancreatic neuroendocrine tumors after initial surveillance or surgical resection: a single-center observational study.

Current guidelines consider observation a reasonable strategy for G1 or G2 nonfunctional pancreatic neuroendocrine tumors (nf pNETs) ≤2 cm. We aimed to characterize their natural behavior and confront the data with the outcomes of patients undergoing upfront surgery. Data from patients with histologically confirmed nf pNETs ≤2 cm, managed at a single tertiary referral center between 2002 and 2020, were retrospectively reviewed. Thirty-nine patients (mean age 62.1 years, 56% male) with 43 lesions (mean size 12.7±3.9 mm; 32 grade 1 [G1] and 7 grade 2 lesions [G2]) were managed by careful surveillance. Progression was observed in 15 lesions (35%; mean follow up 47 months). Six patients (18%) underwent secondary surgery because of an increase in tumor size or dilation of the main pancreatic duct; 3 of them had lymph node metastasis in the resected specimen. Surgery was followed by pancreatic fistula in 2/6 patients, 1 of whom died. Fourteen patients (mean age 59 years, 64.3% female, mean size of lesions 11.4±3.1 mm) underwent pancreatic surgery immediately after diagnosis. The surgery-associated complication rate was 57.1% (8/14). Of the 14 patients, 13 remained recurrence free (mean follow up 67 months). Recurrent metastatic disease was observed 3 years after pancreaticoduodenectomy (R0, 15 mm G2 lesion, 0 N+/8 N) in 1 patient. The behavior of small nf pNETs is difficult to predict, as there is evidence for malignant behavior in a subgroup of patients, even after surgical treatment. Optimal management remains challenging, as pancreatic surgery is associated with significant morbidity.

Evaluation of Treatment Appropriateness in Patients Submitted to Surgery for Non-functioning Pancreatic Neuroendocrine Tumors (NF-PanNETs)

Evaluation of Treatment Appropriateness in Patients Submitted to Surgery for Non-functioning Pancreatic Neuroendocrine Tumors (NF-PanNETs)

Small nonfunctional pancreatic neuroendocrine neoplasms: Time for a step-up treatment approach?

Surgery has been regarded as the only curative treatment for patients with small nonfunctional pancreatic neuroendocrine neoplasms (NF-PNENs) less than 2 cm. Due to the significant adverse event rates of surgery, the European Neuroendocrine Tumor Society issued guidelines favoring surveillance for those patients lacking criteria suggestive of an aggressive disease. Despite the above recommendations, a significant proportion of small NF-PNEN patients still undergo surgery. Recently, several studies have reported the safety and effectiveness of EUS-guided radiofrequency ablation (RFA) for the treatment of small NF-PNENs. The experience with EUS-RFA is, however, limited, but published results indicate a potential role as a minimally invasive alternative treatment for these patients, in particular in those in whom further progression is more probable, before they reach the absolute need for surgery. A step-up approach with EUS-RFA followed by surgery for the failure cases can become a valid option to be validated in clinical studies.

Retracted: Clinicopathological Characteristics of Nonfunctional Pancreatic Neuroendocrine Neoplasms and the Effect of Surgical Treatment on the Prognosis of Patients with Liver Metastases: A Study Based on the SEER Database.

[This retracts the article DOI: 10.1155/2022/3689895.].

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.

Prognostic Significance and Predictors of Nodal Recurrence after Surgery for Non-functioning Pancreatic Neuroendocrine Tumors

Prognostic Significance and Predictors of Nodal Recurrence after Surgery for Non-functioning Pancreatic Neuroendocrine Tumors