Nonfunctioning Pancreatic Neuroendocrine Tumors Research Articles

Comparison of clinical outcomes between enucleation and regular pancreatectomy in patients with non-functional pancreatic neuroendocrine tumors: a retrospective multicenter and propensity score-matched study

There are limited data from retrospective studies on whether therapeutic outcomes after regular pancreatectomy are superior to those after enucleation in patients with small, peripheral and well-differentiated non-functional pancreatic neuroendocrine tumors. This study aimed to compare the short- and long-term outcomes of regular pancreatectomy and enucleation in patients with non-functional pancreatic neuroendocrine tumors. Between January 2007 and July 2020, 227 patients with non-functional pancreatic neuroendocrine tumors who underwent either enucleation (n=89) or regular pancreatectomy (n=138) were included. Perioperative complications, disease-free survival, and overall survival probabilities were compared. Propensity score matching was performed to balance the baseline differences between the two groups. The median follow-up period was 60.76months in the enucleation group and 43.29months in the regular pancreatectomy group. In total, 34 paired patients were identified after propensity score matching. The average operative duration in the enucleation group was significantly shorter than that in the regular pancreatectomy group (147.94±42.39min versus 217.94±74.60min, P<0.001), and the estimated blood loss was also significantly lesser (P<0.001). The matched patients who underwent enucleation displayed a similar overall incidence of postoperative complications (P=0.765), and a comparable length of hospital stay (11.12±3.90days versus 9.94±2.62 days, P=0.084) compared with those who underwent regular pancreatectomy. There were no statistically significant differences between the two groups in disease-free survival and overall survival after propensity score matching. Enucleation in patients with non-functional pancreatic neuroendocrine tumors was associated with shorter operative time, lesser intraoperative bleeding, similar overall morbidity of postoperative complications, and comparable 5-year disease-free survival and overall survival when compared with regular pancreatectomy.

Laparoscopic enucleation of a neuroendocrine tumor on the posterior aspect of the pancreas: Case report and literature review

Introduction. Neuroendocrine tumors of the pancreas are rare neoplasms. They are divided into two groups: functional and non-functional. Non-functional tumors represent a diagnostic challenge, given that they often remain asymptomatic and are diagnosed as an incidental finding. Case outline. We present a patient in whom the tumor was discovered at the junction of the body and the tail of the pancreas, on the dorsal side. The patient had no specific symptomatology, there was no loss in body weight. Considering the diagnostic procedures conducted and the condition of the patient, we decided to perform laparoscopic enucleation. The procedure was carried out in a safe and efficient manner, so that operative and postoperative recovery was uneventful. The definitive histopathological examination confirmed the finding of a non-functional pancreatic neuroendocrine tumor. Conclusion. Laparoscopic enucleation is an effective and safe treatment modality for neuroendocrine tumors of the pancreas with well-known advantages, as compared to open surgery, but there is always a tendency to improve the already existing results and thus to contribute, not only to treatment, but to the greater comfort of the patient.

Comparison between EUS-guided fine-needle aspiration cytology and EUS-guided fine-needle biopsy histology for the evaluation of pancreatic neuroendocrine tumors

Background/objectivesStudies comparing EUS-guided fine-needle aspiration (EUS-FNA) with EUS-guided fine-needle biopsy (EUS-FNB) for the evaluation of pancreatic neuroendocrine tumors (pNETs) are lacking. We aimed at comparing EUS-FNA with EUS-FNB in terms of Ki-67 proliferative index (PI) estimation capability, cellularity of the samples, and reliability of Ki-67 PI/tumor grading compared with surgical specimens. MethodsPatients diagnosed with pNETs on EUS and/or surgical specimens were retrospectively identified. Specimens were re-evaluated to assess Ki-67 PI feasibility, sample cellularity by manual counting, and determination of Ki-67 PI value. Outcomes in the EUS-FNA and EUS-FNB groups were compared. Kendall rank test was used for Ki-67 PI correlation between EUS and surgical specimens. Subgroup analysis including small (≤20 mm), non-functioning pNETs was performed. ResultsThree-hundred samples from 292 lesions were evaluated: 69 EUS-FNA cytology and 231 EUS-FNB histology. Ki-67 PI feasibility was similar for EUS-FNA and EUS-FNB (91.3% vs. 95.7%, p = 0.15), while EUS-FNB performed significantly better in the subgroup of 179 small pNETs (88.2% vs. 96.1%, p = 0.04). Rate of poor cellulated (<500 cells) specimens was equal between EUS-FNA and EUS-FNB. A significant correlation for Ki-67 PI values between EUS and 92 correspondent surgical specimens was found in both groups, but it was stronger with EUS-FNB (tau = 0.626, p < 0.0001 vs. tau = 0.452, p = 0.031). Correct grading estimation was comparable between the two groups (p = 0.482). ConclusionOur study showed stronger correlation for Ki-67 values between EUS-FNB and surgical specimens, and that EUS-FNB outperformed EUS-FNA in the evaluation of small pNETs. EUS-FNB should become standard of care for grading assessment of suspected pNETs.

Management of Asymptomatic Sporadic Nonfunctioning Pancreatic Neuroendocrine Neoplasms (ASPEN) ≤2 cm: Study Protocol for a Prospective Observational Study.

Introduction: The optimal treatment for small, asymptomatic, nonfunctioning pancreatic neuroendocrine neoplasms (NF-PanNEN) is still controversial. European Neuroendocrine Tumor Society (ENETS) guidelines recommend a watchful strategy for asymptomatic NF-PanNEN <2 cm of diameter. Several retrospective series demonstrated that a non-operative management is safe and feasible, but no prospective studies are available. Aim of the ASPEN study is to evaluate the optimal management of asymptomatic NF-PanNEN ≤2 cm comparing active surveillance and surgery.Methods: ASPEN is a prospective international observational multicentric cohort study supported by ENETS. The study is registered in ClinicalTrials.gov with the identification code NCT03084770. Based on the incidence of NF-PanNEN the number of expected patients to be enrolled in the ASPEN study is 1,000 during the study period (2017–2022). Primary endpoint is disease/progression-free survival, defined as the time from study enrolment to the first evidence of progression (active surveillance group) or recurrence of disease (surgery group) or death from disease. Inclusion criteria are: age >18 years, the presence of asymptomatic sporadic NF-PanNEN ≤2 cm proven by a positive fine-needle aspiration (FNA) or by the presence of a measurable nodule on high-quality imaging techniques that is positive at 68Gallium DOTATOC-PET scan.Conclusion: The ASPEN study is designed to investigate if an active surveillance of asymptomatic NF-PanNEN ≤2 cm is safe as compared to surgical approach.

Prognosis after surgery for multiple endocrine neoplasia type 1-related pancreatic neuroendocrine tumors: Functionality matters

BackgroundMetastasized pancreatic neuroendocrine tumors are the leading cause of death in patients with multiple endocrine neoplasia type 1. Aside from tumor size, prognostic factors of pancreatic neuroendocrine tumors are largely unknown. The present study aimed to assess whether the prognosis of patients with resected multiple endocrine neoplasia type 1-related nonfunctioning pancreatic neuroendocrine tumors differs from those with resected multiple endocrine neoplasia type 1-related insulinomas and assessed factors associated with prognosis. MethodsPatients who underwent resection of a multiple endocrine neoplasia type 1-related pancreatic neuroendocrine tumors between 1990 and 2016 were identified in 2 databases: the DutchMEN Study Group and the International MEN1 Insulinoma Study Group databases. Cox regression was performed to compare liver metastases-free survival of patients with a nonfunctioning pancreatic neuroendocrine tumors versus those with an insulinoma and to identify factors associated with liver metastases-free survival. ResultsOut of 153 patients with multiple endocrine neoplasia type 1, 61 underwent resection for a nonfunctioning pancreatic neuroendocrine tumor and 92 for an insulinoma. Of the patients with resected lymph nodes, 56% (18/32) of nonfunctioning pancreatic neuroendocrine tumors had lymph node metastases compared to 10% (4/41) of insulinomas (P = .001). Estimated 10-year liver metastases-free survival was 63% (95% confidence interval 42%–76%) for nonfunctioning pancreatic neuroendocrine tumors and 87% (72%–91%) for insulinomas. After adjustment for size, World Health Organization tumor grade, and age, nonfunctioning pancreatic neuroendocrine tumors had an increased risk for liver metastases or death (hazard ratio 3.04 [1.47–6.30]). In pancreatic neuroendocrine tumors ≥2 cm, nonfunctioning pancreatic neuroendocrine tumors (2.99 [1.22–7.33]) and World Health Organization grade 2 (2.95 [1.02–8.50]) were associated with liver metastases-free survival. ConclusionPatients with resected multiple endocrine neoplasia type 1-related nonfunctioning pancreatic neuroendocrine tumors had a significantly lower liver metastases-free survival than patients with insulinomas. Postoperative counseling and follow-up regimens should be tumor type specific and at least consider size and World Health Organization grade.

Endoscopic ultrasound-guided radiofrequency ablation of pancreatic neuroendocrine tumors: a systematic review of the literature.

Background and study aims Surgery is the mainstay therapy for pancreatic neuroendocrine tumors (P-NETs), but it is associated with significant adverse events (AEs). In recent years, endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has been described for treating P-NETs. We performed a systematic literature review aimed at exploring the feasibility, effectiveness, and safety of EUS-RFA in treatment of P-NETs. Methods The literature review was performed in PubMed/MEDLINE, EMBASE, and SCOPUS to identify all case reports of EUS-RFA for treatment of P-NETs. Results Sixyt-one patients (males 49.2 %, mean age 64.5 years) and 73 tumors (mean size 16 mm, insulinomas 30.1 %) treated with EUS-RFA were included from 12 studies. The overall effectiveness of EUS-RFA was 96 % (75 % – 100 %) without differences between functional vs. non-functional P-NETs ( P = 0.3) and without relevant issues about safety (mild AEs 13.7 %). While tumor location was not predictive for incomplete/non-response to EUS-RFA, greater tumor dimensions predicted treatment failure (21.8 ± 4.71 mm in the non-response group vs 15.07 ± 7.34 mm in the response group, P = 0.048). At ROC analysis, a P-NET size cut-off value ≤18 mm predicted response to treatment, with a sensitivity of 80 % (95 % CI 28.4 % – 99.5 %), a specificity of 78.6 % (95 % CI 63.2 % – 89.7 %), a positive predictive value of 97.1 % (95 % CI 84.7 % – 99.9 %) and a negative predictive value of 30.8 % (95 % CI 9.1 % – 61.4 %), with an area under the curve of 0.81 (95 % CI 0.67 – 0.95). Conclusions EUS-RFA is safe and effective for treating P-NETs. It may be reasonable to consider EUS-RFA for small P-NETs, irrespective of the functional status.

A comprehensive validation of the novel 8th edition of American Joint Committee on Cancer staging manual for the long-term survivals of patients with non-functional pancreatic neuroendocrine neoplasms.

Histologically, the World Health Organization has classified pancreatic neuroendocrine neoplasms (p-NENs) into well-differentiated pancreatic neuroendocrine tumors (G1/G2 p-NETs) and poorly-differentiated pancreatic neuroendocrine carcinoma (G3 p-NECs) based on tumor mitotic counts and Ki-67 index. Recently, the 8th edition of American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging manual has incorporated some major changes in 2017 that the TNM staging system for p-NENs should only be applied to well-differentiated G1/G2 p-NETs, while poorly-differentiated G3 p-NECs be classified according to the new system for pancreatic exocrine adenocarcinomas. However, this new manual for p-NENs has seldom been evaluated.Data of patients with both G1/G2 and G3 non-functional p-NENs (NF-p-NENs) from our institution was retrospectively collected and analyzed using 2 new AJCC 8th staging systems. We also made survival comparisons between the 8th and 7th edition system separately for different subgroups.For G1/G2 NF-p-NETs, there were 52 patients classified in AJCC 8th edition stage I, 40 in stage II, 41 in stage III and 19 in stage IV. As for G3 NF-p-NECs, 17, 19, 24, and 18 patients were respectively defined from AJCC 8th edition stage I to stage IV. In terms of the AJCC 7th staging system, the 230 patients with NF-p-NENs were totally distributed from stage I to stage IV (94, 63, 36, 37, respectively). For the survival analysis of both G1/G2 NF-p-NETs and G3 NF-p-NECs, the AJCC 7th edition system failed to discriminate the survival differences when compared stage III with stage II or stage IV (P > .05), while the 8th edition ones could perfectly allocate patients into 4 statistically different groups (P < .05). The HCIs of AJCC 8th stage for G1/G2 NF-p-NETs [HCI=0.658, 95% confidence interval (CI)=0.602-0.741] and stage for G3 NF-p-NECs (HCI=0.704, 95% CI=0.595-0.813) was both statistically larger than those of AJCC 7th stage for different grading NF-p-NENs [(HCI=0.578, 95% CI=0.557-0.649; P=.031), (HCI=0.546, 95% CI=0.531-0.636; P = .019); respectively], indicating a more accurate predictive ability for the survivals of NF-p-NENs.Our data suggested the 2 new AJCC 8th staging systems were superior to its 7th edition for patients with both G1/G2 NF-p-NETs and G3 NF-p-NECs.

Minimally invasive vs open pancreatectomy for nonfunctioning pancreatic neuroendocrine tumors.

BACKGROUNDThe mainstay of treating nonfunctioning-pancreatic neuroendocrine tumors(NF-PNETs) is surgical resection. However, minimally invasive approaches to pancreatic resection for treating NF-PNETs are not widely accepted, and the long-term oncological outcomes of such approaches remain unknown.AIMTo determine the short- and long-term outcomes of minimally invasive pancreatic resection conducted in patients with NF-PNETs.METHODSProspective databases from Severance Hospital were searched for 110 patients who underwent curative resection for NF-PNETs between January 2003 and August 2018.RESULTSThe proportion of minimally invasive surgery (MIS) procedures performed for NF-PNET increased to more than 75% after 2013. There was no significant difference in post-operative complications (P = 0.654), including pancreatic fistula (P = 0.890) and delayed gastric emptying (P = 0.652), between MIS and open approaches. No statistically significant difference was found in disease-free survival between the open approach group and the MIS group (median follow-up period, 28.1 mo; P = 0.428). In addition, the surgical approach (MIS vs open) was not found to be an independent prognostic factor in treating NF-PNET patients [Exp(β) = 1.062; P = 0.929].CONCLUSIONRegardless of the type of surgery, a minimally invasive approach can be safe and feasible for select NF-PNET patients.

Lanreotide autogel/depot in advanced enteropancreatic neuroendocrine tumours: final results of the CLARINET open-label extension study

PurposeIn the phase III CLARINET study (NCT00353496), lanreotide autogel/depot (lanreotide) significantly improved progression-free survival (PFS) vs placebo in patients with non-functioning intestinal or pancreatic neuroendocrine tumours (NETs). The aim of CLARINET open-label extension (OLE) (NCT00842348) was to evaluate long-term safety and efficacy of lanreotide in these patients.MethodsPatients from the CLARINET study were eligible for the OLE if they had stable disease (irrespective of treatment group) or progressive disease (PD) (placebo-treated patients only). All patients in the OLE received lanreotide 120 mg every 28 days. Computed tomography or magnetic resonance imaging scans were conducted every 6 months and assessed locally for PD (the final scan was also assessed centrally).ResultsOverall, 89 patients took part in the OLE (lanreotide, n = 42; placebo, n = 47). Median (range) exposure to lanreotide in patients who received lanreotide in the core study and OLE (LAN–LAN group) was 59.0 (26.0–102.3) months. In this group, the overall incidences of adverse events (AEs) and treatment-related AEs were lower in the OLE than in the core study. Median [95% CI] PFS in the LAN–LAN group was 38.5 [30.9; 59.4] months. In placebo-treated patients with PD at the end of the core study, time to death or subsequent PD during the OLE was 19 [10.1; 26.7] months.ConclusionsThis study provides new evidence on the long-term safety profile and sustained anti-tumour effects of lanreotide autogel/depot in indolent and progressive metastatic intestinal or pancreatic NETs.

Infiltrating pattern and prognostic value of tertiary lymphoid structures in resected non-functional pancreatic neuroendocrine tumors

BackgroundTertiary lymphoid structures (TLS) are associated with favorable survival and play a critical role in most solid tumors. However, investigations of TLS are lacking in patients with grade 1 or...

Hot topic in the comprehensive treatment of pancreatic neuroendocrine tumors

The incidence of pancreatic neuroendocrine tumor is increasing gradually in recent years.There are still lots of debated issues in surgical management of this kind of tumor.Whether all small non-functional pancreatic neuroendocrine tumor need to be resected, whether primary and metastatic lesion need to be resected in metastatic disease, whether adjuvant therapy is necessary for resected tumor, whether enucleation is optimal for small pancreatic neuroendocrine tumor.Some data from real world study has provide primary answer to these questions.More high-quality study in the future will provide satisfactory answer.

EUS-guided fine needle tattooing (EUS-FNT) for preoperative localization of small pancreatic neuroendocrine tumors (p-NETs): a single-center experience.

and study aims Pancreatic neuroendocrine tumors (pNETs) can be difficult to detect intra-operatively. The aim of this paper is to evaluate the safety and efficacy of preoperative endoscopic ultrasound guided fine needle tattooing (EUS-FNT) to facilitate intra-operative detection of pNETs. Sixteen patients with pNETs (8 insulinoma and 8 non-functional pancreatic neuroendocrine tumors) underwent EUS-FNT. The procedure was carried out using the conventional curvilinear EUS. Tattooing was performed by intralesional injection of 1-2mL of Spot® ink (Spot®, GI Supply, Comp Hill, PA, US) using a standard 22 gauge EUS-FNA needle. All identified pNETs could be tattooed in one session. The procedure was well tolerated in all patients without any complication. The time interval between tattooing and surgery was between 1 and 565days (mean of 52days). Nine patients underwent open and seven laparoscopic surgery. The tattooed lesions could be recognized in all but one patient. In one patient, a small hematoma secondary to the EUS-FNT was observed. Pathological examination of the resection specimen showed local R0 resection in all cases, and no interference with the specimen evaluation was encountered. Our results suggest that EUS-guided FNT is a safe and useful method to mark preoperatively small (≤ 2cm) pNETs.

Pancreatic insufficiency following pancreatectomy: Does underlying tumor syndrome confer a greater risk?

BackgroundThe risk of postoperative pancreatic exocrine insufficiency (PPEI) is unknown in patients with multiple endocrine neoplasia type I (MEN1) and von Hippel-Lindau (VHL) who require resection of pancreatic neuroendocrine tumors (PNETs). MethodsA retrospective review of patients who underwent resection of PNETs at the National Institutes of Health from 2007 to 2019 was performed. ResultsOur cohort included 82 patients (VHL n = 25, MEN1 n = 20, sporadic n = 37), 6 of whom developed PPEI. While VHL compared to all non-VHL patients (p = 0.046), non-functional PNETs (p = 0.050), and pancreaticoduodenectomy (PD) (p=<0.001) were associated with higher rates of PPEI on univariate analysis, only PD was found to be an independent predictor of PPEI on multivariate analysis (OR 14.43, 95% CI 1.43–145.8, p = 0.024). ConclusionsThe rate of PPEI in patients with hereditary tumor syndromes was similar to that of sporadic PNETs. PD was independently associated with PPEI, and this increased risk should be included in preoperative counseling.

Metastatic insulinoma presenting 14 years after benign tumour resection: a rare case and management dilemma.

SummaryWe present a 60-year-old woman who underwent successful surgical resection (partial pancreatectomy) for a low grade non-functioning pancreatic neuroendocrine tumour (pNET), with no biochemical or radiological features of recurrence on follow-up visits for 5 years. Fourteen years after the initial surgery, she developed spontaneous severe hypoglycaemic episodes which required hospitalisation, with subsequent investigations confirming the diagnosis of a metastatic insulin-secreting pNET (insulinoma). Medical management of her severe spontaneous hypoglycaemic episodes remained challenging, despite optimum use of diazoxide and somatostatin analogue therapy. Based on a discussion at the regional neuroendocrine tumour multidisciplinary team meeting, she underwent an elective hepatic trans-arterial embolization which was unfortunately unsuccessful. She ended up requiring an emergency right hemihepatectomy and left retroperitoneal mass resection which finally stabilised her clinical condition.Learning points:Ours is only the seventh case report of a previously benign pNET presenting as a functional insulin secreting metastatic tumour. However, it is the first case report, in which the metastatic functional pNET presented after such a long hiatus (14 years).There is currently no clear consensus regarding the length of follow-up of non-functional pNET which are deemed cured post-surgical resection, with most guidelines advocating a median follow up of 5 years (1). The delayed presentation in our case suggests additional considerations should be made regarding optimal post-operative surveillance duration based on the age of the patient, location of the tumour, lymph node spread and Ki-67 index.Hepatic artery embolization and/or partial hepatectomy remains a treatment option for pNET patients with significant hepatic metastasis.

Magnetic resonance imaging radiomic analysis can preoperatively predict G1 and G2/3 grades in patients with NF-pNETs.

We aimed to explore the relationship between the magnetic resonance imaging (MRI) radiomic score (rad-score) and the grades of non-functioning pancreatic neuroendocrine tumors (NF-pNETs) and evaluate the potential of the calculated MRI rad-score to differentiate grade 1 from grade 2/3 NF-pNETs. This retrospective study assessed 157 patients with surgically resected, pathologically confirmed NF-pNETs who underwent magnetic resonance scans from November 2012 to December 2019. Radiomic features were extracted from arterial and portal venous MRI. The least absolute shrinkage and selection operator method were used to select the features. Multivariate logistic regression models were used to analyze the association between the MRI rad-score and NF-pNET grades. The MRI rad-score performance was assessed based on its discriminative ability and clinical usefulness. The MRI rad-score, which consisted of seven selected features, was significantly associated with the NF-pNET grades. Every 1-point increase in the rad-score was associated with a 35% increased risk of grade 2/3 disease. The score also showed high accuracy (area under the curve = 0.775). The best cut-off point for maximal sensitivity and specificity was at 0.41. In the decision curves, when the threshold probability was higher than 0.3, the rad-score used in this study to distinguish grades 1 and 2/3 NF-pNETs offered more benefits than the use of a treat-all-patients or a treat-none scheme. The MRI rad-score showed a significant association with the grades of NF-pNETs. Thus, it may be used as a valuable non-invasive tool for differential NF-pNET grading.

The Clinical Features and Molecular Mechanisms of ACTH-secreting Pancreatic Neuroendocrine Tumors.

Pancreatic neuroendocrine tumors (pNETs) causing ectopic adrenal corticotropic hormone (ACTH) syndrome (EAS) are rare and aggressive with little known information. We aimed to elucidate the clinical features and molecular mechanisms of pNETs with EAS by methylation analysis. Seven patients with ectopic ACTH-secreting pNETs who were diagnosed at Shanghai Clinical Endocrine and Metabolic Diseases Center and Pancreatic Disease Center in Ruijin Hospital between 2001 and 2019 were enrolled. Twenty patients with ectopic ACTH-secreting thymic neuroendocrine tumors (TNETs) and 7 with nonfunctional pNETs (nf-pNETs) were also enrolled as controls. We collected clinical data and measured POMC promoter CpG methylation. All 7 patients had elevated ACTH and urinary free cortisol (UFC) levels with positive ACTH staining in the pancreas and were diagnosed with ectopic ACTH-secreting pNET. Of the 7 patients, 6 underwent surgery and 1 underwent transarterial embolization (TAE). Two patients were free of disease after surgery; 2 died within 90 days after surgery; and 3 had metastases and died within 1 year. Compared with ACTH-secreting TNETs, ACTH-secreting pNETs had similar clinical and biochemical features but a significantly poorer prognosis. POMC promoter CpG methylation was significantly lower in ACTH-secreting pNETs than in nf-pNETs and normal pancreas. ACTH-secreting pNETs are aggressive and fatal. Surgery is definitively curative for patients with resectable primary tumors without metastasis. Pro-opiomelanocortin (POMC) promoter hypomethylation caused pNETs to produce ACTH. This study further supplements the genetic features of ACTH-secreting NETs.

Role of Pre-operative Inflammatory Markers as Predictors of Lymph Node Positivity and Disease Recurrence in Well-Differentiated Pancreatic Neuroendocrine Tumours: Pancreas2000 Research and Educational Program (Course 9).

Pancreatic neuroendocrine tumours (PNET) is a rare disease and in the absence of metastases, surgical resection is recommended. Key factors affecting survival in PNETs are the stage and grade of the disease, but there is increasing evidence suggesting lymph node involvement is associated with shorter disease-free and overall survival. Ability to predict the likelihood of lymph node involvement at the time of diagnosis would affect surgical decision making in these patients. A systemic inflammatory index such as neutrophil to lymphocyte ratio or platelet to lymphocyte ratio has been associated with poor prognosis in several cancers.Method: This study is a retrospective multi-centre study. The data including pre-operative inflammatory markers such as haemoglobin, neutrophil, lymphocyte counts and pathological data including number of positive lymph nodes, tumour grade and size, are collected to assess the association between inflammatory index and lymph node involvement.Conclusion: This study aims to assess the value of routinely available pre-operative haematological markers in predicting lymph node involvement in non-functioning PNETs.

Pattern of disease recurrence and treatment after surgery for nonfunctioning well-differentiated pancreatic neuroendocrine tumors

BackgroundThe risk of recurrence after curative surgery for pancreatic neuroendocrine tumors is reported to be between 10% and 30%. Among the available locoregional and systemic treatments, there are no specific recommendations regarding the best option for treating recurrent disease. The aims of this study were to evaluate the pattern of recurrence after surgery performed with curative intent for nonfunctioning pancreatic neuroendocrine tumors and to analyze the impact of treatment on disease progression. MethodsAll patients submitted to curative surgery for sporadic, well-differentiated, nonfunctioning pancreatic neuroendocrine tumors at 2 Italian centers between 2001 and 2018, with evidence of disease recurrence during follow-up, were included (n = 46). ResultsThe most frequent type of recurrence was distant metastases (n = 38, 83%), located in the liver in 100% of cases, whereas 8 patients (17%) had an isolated local recurrence. Therapy for first disease recurrence included both locoregional (n = 14) and systemic treatments (n = 32). A second disease recurrence/progression occurred in 28 patients (61%). Patients who underwent systemic treatment after the first disease recurrence had better progression-free survival (1-year progression-free survival 78%) compared with those submitted to a locoregional procedure (1-year progression-free survival 50%; P = .007). Independent predictors of shortened progression-free survival after the first disease recurrence were the type of treatment (locoregional, hazard ratio 4.452, P = .001), the presence of necrosis (hazard ratio 2.732, P = .022) and age (>60 year, hazard ratio 2.494, P = .040). ConclusionUpfront locoregional treatment of the first recurrence of nonfunctioning pancreatic neuroendocrine tumors after curative surgery should be avoided in favor of systemic therapy.

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.

CT-Based Radiomics Score for Distinguishing Between Grade 1 and Grade 2 Nonfunctioning Pancreatic Neuroendocrine Tumors.

OBJECTIVE. The objective of our study was to explore the relationship between a CT-based radiomics score and grade of nonfunctioning pancreatic neuroendocrine tumors (PNETs) and to evaluate the ability of a calculated CT radiomics score to distinguish between grade 1 and grade 2 nonfunctioning PNETs. MATERIALS AND METHODS. This retrospective study assessed 102 patients with surgically resected, pathologically confirmed nonfunctioning PNETs who underwent MDCT from January 2014 to December 2017. Radiomic methods were used to extract features from portal venous phase CT scans, and the least absolute shrinkage and selection operator (LASSO) method was used to select the features. Multivariate logistic regression models were used to analyze the association between the CT radiomics score and nonfunctioning PNET grades. The performance of the CT radiomics score was assessed on the basis of its discriminative ability and clinical usefulness. RESULTS. The CT radiomics score, which consisted of four selected features, was significantly associated with nonfunctioning PNET grades. Every 1-point increase in radiomics score was associated with a 57% increased risk of grade 2 disease. The score also showed high accuracy (AUC = 0.86 for all PNETs; AUC = 0.81 for PNETs ≤ 2 cm). The best cutoff point for maximal sensitivity and specificity was a CT radiomics score of -0.134. Decision curve analysis showed that the CT radiomics score is clinically useful. CONCLUSION. The CT radiomics score shows a significant association with the grade of nonfunctioning PNETs and provides a potentially valuable noninvasive tool for distinguishing between different grades of nonfunctioning PNET, especially among patients with tumors 2 cm or smaller.