Small Nonfunctional Pancreatic Neuroendocrine Tumors Research Articles

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.

Propensity score-matched analysis of clinical outcome after enucleation versus regular pancreatectomy in patients with small non-functional pancreatic neuroendocrine tumors

ObjectivesThe effectiveness of enucleation in treatment for low-grade (G1, G2) small (≤2 cm) non-functional pancreatic neuroendocrine tumors (sNF-pNETs) remains controversial. This study investigated short- and long-term outcome of enucleation comparing with regular pancreatectomy in patients with sNF-pNETs. MethodsThe clinical data of patients with sNF-pNETs who underwent surgery in our hospital from January 2000 to December 2017 were retrospectively collected. Short- and long-term outcomes of two operations were analyzed. The propensity score matching (PSM) was performed to reduce potential selection bias. ResultsA total of 123 patients with sNF-pNETs were enrolled with 62 males, 69 G1, and median age was 56.91 ± 10.04 years old. During the follow-up period (mean 87 ± 58.1 months), 9(7.32%) disease progressed (recurrence or metastasis) and 2 died (1.62%), 5-years OS was 100%, 5-years DFS was 91.4%. Both lymph node metastasis (p = 0.117) and pathological grade (p = 0.050) were not prognostic factors for sNF-pNETs. The propensity score–matched cohort comprised 27 patients with enucleation and 44 patients with regular pancreatectomy. Enucleation was noninferior to regular pancreatectomy in terms of DFS, before or after PSM. The surgical duration (P < 0.01) and blood loss (P < 0.01) significantly decreased in enucleation compared with regular pancreatectomy. The other postoperative complications tended to occur in regular pancreatectomy than in enucleation, but no statistically significant difference (all p > 0.05). ConclusionEnucleation seems to be an effective option for the treatment of sNF-pNETs with a lower total rate of postoperative complications and similar long-term prognosis, compared with regular pancreatectomy.

DAXX mutations as potential genomic markers of malignant evolution in small nonfunctioning pancreatic neuroendocrine tumors

Management of localized well-differentiated pancreatic neuroendocrine tumors (panNETs) is controversial and primarily dependent on tumor size. Upfront surgery is usually recommended for tumors larger than 2 cm in diameter since they frequently show metastatic potential, whereas smaller panNETs are generally characterized by an indolent clinical course, with a rate of relapse or metastasis below 15%. To explore whether increased tumor size is paralleled by genomic variations, we compared the rate and the mutational patterns of putative driver genes that are recurrently altered in these tumors by investigating differential cohorts of panNET surgical specimens smaller (n = 27) or larger than 2 cm (n = 29). We found that the cumulative number of mutations detected in panNETs >2 cm was significantly higher (p = 0.03) relative to smaller tumors, while mutations of DAXX were significantly more frequent in the cohort of larger tumors (p = 0.05). Moreover, mutations of DAXX were associated with features of malignancy including increased grade, nodal involvement and lymphovascular invasion, and independently predicted both relapse after surgery (p = 0.05) and reduced DFS in multivariable analysis (p = 0.02). Our data suggest that alterations of the DAXX/ATRX molecular machinery increase the malignant potential of panNETs, and that identification of mutations of DAXX/ATRX in small, nonfunctioning tumors can predict the malignant progression observed in a minority of them.

Management of small asymptomatic nonfunctioning pancreatic neuroendocrine tumors: from guidelines to real life

Management of small asymptomatic nonfunctioning pancreatic neuroendocrine tumors: from guidelines to real life

Management of small asymptomatic nonfunctioning pancreatic neuroendocrine tumors: Limitations to apply guidelines into real life

BackgroundInternational guidelines suggest a watchful strategy for small nonfunctioning pancreatic neuroendocrine tumors. The aim of this study was to evaluate the management and indications for surgery in patients with asymptomatic nonfunctioning pancreatic neuroendocrine tumors ≤2 cm. MethodsPatients with asymptomatic, incidental, sporadic nonfunctioning pancreatic neuroendocrine tumors ≤2 cm without nodal or distant metastases were included (2012–2016). A comparison between active surveillance and surgery groups was performed. ResultsOf the 101 included patients, 72% underwent active surveillanc and 28% were surgically treated. Patients submitted to surgery were significantly younger (53 vs 60 years, P = .013), had a higher incidence of positive 18F-fluorodeoxyglucose positron emission tomography (18% vs 50%, P = .003), and a higher incidence of cytologically determined G2 tumor (0% vs 14%, P = .008). Conservatively managed patients had a significantly smaller tumor size (12 vs 16 mm, P = .0001). The main reasons determining surgical choice were as follows: patient’s preference (32%), positive 18F-fluorodeoxyglucose positron emission tomography (21.5%), main pancreatic duct dilation (17.5%), cytologically determined G2 tumor (14.5%), and young age (14.5%). At a median follow-up of 40 months, all of the 73 patients conservatively managed were alive, with no evidence of distant metastases and none underwent surgery. Only 5 patients had a tumor growth >20%. ConclusionOne-third of patients with asymptomatic small nonfunctioning pancreatic neuroendocrine tumors ≤2 cm underwent surgery. Patient’s preference, initial tumor size, and young age were the main determinants of surgical indication. Preoperative diagnostic workup, including 18F-fluorodeoxyglucose positron emission tomography and cytologic grading, seems to be poorly accurate in determining malignant features in these small lesions.

Prognosis of sporadic resected small (≤ 2 cm) nonfunctional pancreatic neuroendocrine tumors - a multi-institutional study

Background: Non-functional pancreatic neuroendocrine tumors (NF-PNET) are rare tumors increasingly being diagnosed incidentally. Choice of treatment for small (2cm or less) NF-PNETs is difficult as their malignant potential is difficult to predict. This is reflected in the current recommendations - some favor surgery, while others suggest wait-and-see policy [1–6]. As these tumors are rare, previous clinical series are small. The aim of this study was to identify factors affecting prognosis after surgery for small NF-PNETs in a multicenter study. Methods: Patients were identified from the databases of 16 European centers and data was extracted retrospectively. Uni- and multivariate (Cox) analyses were used to identify risk factors for recurrence. Results: 210 patients (median age 60y) were included. Median tumor size was 15mm, 65% were asymptomatic, and 42% underwent parenchyma-sparing surgery. Severe mordibidity was noted in 14% and 1 patient died postoperatively. 10% had metastatic lymph nodes. 5-year disease-free survival was excellent, 93.5%. Tumor size, presence of bile or pancreatic duct dilation, and WHO grade 2 -3 were identified as independent risk factors for recurrence. Tumors <11mm in size did not recur during follow-up. Parenchyma-sparing pancreatectomy carried highest risk for pancreatic fistula, but was also associated with favorable disease-free survival. Conclusion: Presence of bile or pancreatic duct dilation or WHO grade 2-3 advocate for surgical treatment of small (2cm or less) NF-PNETs.

Prognosis of sporadic resected small (≤ 2 cm) nonfunctional pancreatic neuroendocrine tumors – A multi-institutional study

Prognosis of sporadic resected small (≤ 2 cm) nonfunctional pancreatic neuroendocrine tumors – A multi-institutional study

Natural History of Small Pancreatic Lesions Suspected to Be Nonfunctioning Pancreatic Neuroendocrine Tumors.

Nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) are a rare disease but have been diagnosed more frequently than before. The aim of this study was to evaluate the natural course of small NF-PNETs. We performed a retrospective analysis of patients with incidentally found small NF-PNETs (<20 mm) from 1999 to 2015. The patients who were recommended surveillance were included. There were 69 patients with small NF-PNETs with a mean size of 10.9 (standard deviation [SD], 3.1) mm. The average follow-up period was 52.2 (SD, 38.7) months. The changes in tumor size were as follows: increased (13.0%), sustained (84.1%), and decreased (2.9%). Eighteen were evaluated with grade 1 NF-PNETs and 1 with grade 2 among the obtained tissues. Thirteen patients underwent surgery after an average 32.9 (SD, 42.6) months later. There were 7 patients of Ia, 1 of Ib, 2 of IIa, and 1 of IIb according to the pathologic stages. Two patients received reoperation for recurrent tumors, and 2 patients showed distant metastasis after surgery, but no disease-related death occurred. Most of the small NF-PNETs did not increase in size and seldom showed metastasis. The wait-and-see strategy can be used for NF-PNETs less than 2 cm.

Prognostic factors of small non-functional pancreatic neuroendocrine tumors

Objective To investigate the clinical features and prognostic factors of small (maximum diameter≤2.0 cm) non-functional pancreatic neuroendocrine tumors (NF-PNET). Methods From January 2002 to April 2017, the clinical data of 18 patients with small NF-PNET were retrospectively analyzed. The prognosis and clinical pathological features were investigated. According to the prognosis, the patients were divided into death group (four cases) and disease-free survival group (14 cases). Fisher′s exact test and Mann-Whitney rank inspection were performed for statistical analysis. Results All 18 patients (nine males, nine females) aged 23 to 80 years old, median age 52.5 years old received radical resection. The median follow-up time was 54 months. Four patients died during the follow-up. There was no statistically significant difference in median age (61.0 years, 32.0 to 80.0 years vs 49.0 years, 23.0 to 72.0 years) and median tumor maximum diameters (1.9 cm, 0.8 to 2.0 cm vs 1.5 cm, 0.8 to 2.0 cm) between the death group and disease-free survival group (Z=-1.223 and -0.752, P=0.233 and 0.505). Compared with that of disease-free survival group, tumor differentiation degree of the death group was lower (poor/high differentiation, 2/2 vs 0/14), and the difference was statistically significant (Fisher′s exact test, P=0.039). However, there was no significant difference in histological grades (G1/G2/G3, 1/1/2 vs 9/5/0; Fisher′s exact test, P=0.057). The distribution of tumor in death group and disease-free survival group was similar. The proportion of patients with tumor at pancreatic head was 2/4 and 6/14 of the death group and disease-free survival group, respectively. The surgical methods of the death group included pancreaticoduodenectomy (two cases), distal pancreatectomy (one case), and total pancreatectomy (one case), and there was no statistically significant difference in rates of surgical methods between the two groups (Fisher′s exact test, P=0.260). Conclusion Age, tumor maximum diameter, degree of differentiation, histological grade and surgical methods may be correlated with poor prognosis of small NF-PNET. Key words: Neuroendocrine tumors; Risk factors; Prognosis; Pancreatic neuroendocrine tumor

Natural history of small nonfunctioning pancreatic neuroendocrine tumors.

515 Background: Asymptomatic sporadic nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) are rare disease but are diagnosed more frequently than before. The aim of this study was to evaluate the natural course of small NF-PNETs. Methods: We performed retrospective study of patients with suspected NF-PNETs from 1999 to 2015. Patients older than 18 years with NF-PNETs diagnosed either by pathology or other clinical evidences were included. Patients with clinical symptoms of hormonal hypersecretion, more than 20 mm in size, local invasion, nodal or distant metastasis, less than two follow-up imaging studies , and follow-up period of less than 6 months were excluded. Results: Small NF-PNETs in patients initially recommended surveillance (n = 69; mean age, 58.9 ± 11.1 yrs) were mainly located in the pancreatic head (n = 32, 46.4%) with mean mass size of 10.9 ± 3.1 mm. The average follow-up period was 52.2 ± 38.7 months. Tumor size changes during the follow-up period were as follows: increased (n = 9, 13.0%), sustained (n = 58, 84.1%), decreased (n = 2, 2.9%). The mean growth rate of increasing tumor was 0.9 ± 2.9 mm/year. Non-hypervascular tumors showed a tendency to increase in size compared to hypervascular tumor. (P = 0.04) Thirteen patients (18.8%) underwent surgery during the follow-up at average 32.9 ± 42.6 months later. According to the WHO 2010 grade classification, grade 1 was found in 18 patients, grade 2 in 1 patient, and grade 3 in 0 patient. The pathologic AJCC TNM stages of surgically resected tumors were Ia in 7 patients, Ib in 1 patient, IIa in 2 patient, IIb in 1 patients. Two patients (10.0%) received reoperation for recurred tumors at 34 and 50 months after surgery. Two patients (2.9%) showed distant metastasis after surgery but no disease-related death occurred. Conclusions: Most of small NF-PNETs do not increase in the size and seldom show metastasis during follow-up. Wait-and-see strategy can be applied for NF-PNETs less than 2cm in size.

Prognosis of sporadic resected small (≤2 cm) nonfunctional pancreatic neuroendocrine tumors – a multi-institutional study

BackgroundMalignant potential of small (≤20 mm) nonfunctional pancreatic neuroendocrine tumors (sNF-PNET) is difficult to predict and management remain controversial. The aim of this study was to assess the prognosis of sporadic nonmetastatic sNF-PNETs. MethodsPatients were identified from databases of 16 centers. Outcomes and risk factors for recurrence were identified by uni- and multivariate analyses. ResultssNF-PNET was resected in 210 patients, and 66% (n = 138) were asymptomatic. Median age was 60 years, median tumor size was 15 mm, parenchyma-sparing surgery was performed in 42%. Postoperative mortality was 0.5% (n = 1), severe morbidity rate was 14.3% (n = 30), and 14 of 132 patients (10.6%) with harvested lymph nodes had metastatic lymph nodes. Tumor size, presence of biliary or pancreatic duct dilatation, and WHO grade 2–3 were independently associated with recurrence. Patients with tumors sized ≤10 mm were disease free at last follow-up. The 1-, 3- and 5-year disease-free survival rates for patients with tumors sized 11–20 mm on preoperative imaging were 95.1%, 91.0%, and 87.3%, respectively. ConclusionsIn sNF-PNETs, the presence of biliary or pancreatic duct dilatation or WHO grade 2–3 advocate for surgical treatment. In the remaining patients, a wait-and-see policy might be considered.

Long-Term Natural Course of Small Nonfunctional Pancreatic Neuroendocrine Tumors in MEN1-Results From the Dutch MEN1 Study Group.

Pancreatic neuroendocrine tumors (pNETs) are highly prevalent in patients with multiple endocrine neoplasia type 1 (MEN1), and metastatic disease is an important cause of MEN1-related mortality. Especially small nonfunctional (NF) pNETs pose a challenge to the treating physician and more information is needed regarding their natural course. We assessed long-term natural history of small NF-pNETs and its modifiers in the Dutch MEN1 population. Retrospective longitudinal observational cohort study of patients with small (<2 cm) NF-pNETs from the Dutch national MEN1 database, which includes >90% of the Dutch MEN1 population. Modifiers of long-term natural course were analyzed using linear mixed-models analysis. Growth rate of the 115 included small NF-pNETs from 99 patients was slow (0.4 mm/y; 95% confidence interval, 0.15 to 0.59). Seventy percent of the tumors was stable and a subgroup of 30% of the tumors was growing (1.6 mm/y; 95% confidence interval, 1.1 to 2.0). No differences in clinical characteristics were identified between growing and stable tumors. Within the subgroup of growing tumors, germline missense mutations were significantly associated with accelerated growth compared with nonsense and frameshift mutations. The majority of small NF-pNETs are stable at long-term follow-up, irrespective of the underlying MEN1 genotype. A subgroup of tumors is slowly growing but cannot be identified on clinical grounds. In this subgroup, tumors with missense mutations exhibited faster growth. Additional events appear necessary for pNETs to progress. Future studies should be aimed at identifying these molecular driving events, which could be used as potential biomarkers.

Nonfunctioning, Small, Incidental Pancreatic Neuroendocrine Tumors: Results of a Nonoperative Approach Cohort

ObjectiveThe availability of new imaging techniques has conditioned an increase in the incidental diagnosis of small nonfunctioning pancreatic neuroendocrine tumors (PNET-NF). The best treatment is controversial, some authors advise a conservative approach in selected cases. Our aim is to analyze the evolution of incidental, small size PNET-NF, treated with clinical follow-up without surgery. MethodsWe performed a retrospective analysis of a prospective database of patients diagnosed incidentally with PNET-NF since November 2007 to September 2015. We include those with PNET-NF ≤2cm and asymptomatic. The diagnosis was performed using imaging tests indicating endoscopic ultrasound-guided fine-needle aspiration in case of doubts in the diagnosis. The follow-up was performed at our center, registering clinical and/or radiological changes. ResultsWe included 24 patients with a median age of 70 years, and a similar distribution in terms of sex. The diagnosis was made through computed tomography multidetector or magnetic resonance imaging and octreotide scan. The tumors were located mainly in the head and neck (46%), with a mean size of 11.5±3.55mm at diagnosis (5–19mm). In 2 cases endoscopic ultrasound fine needle aspiration was used (8%), confirming the diagnosis of low-grade PNET with Ki67 <5%. The median follow-up was 39 months (7–100). In 19 patients (79%) they remained the same size, 21% (5) increased its size with a mean of 2.6±2mm (1–6). No cases had progression of disease. ConclusionIn selected patients, non-surgical management of PNET-NF is an option to consider, when they are asymptomatic and ≤2cm. Larger studies with more patients and more time of follow-up are needed to validate this non-operative approach.

Tumores neuroendocrinos no funcionantes de páncreas incidentales de pequeño tamaño: Resultados de una serie con manejo no quirúrgico

ObjectiveThe availability of new imaging techniques has conditioned an increase in the incidental diagnosis of small nonfunctioning pancreatic neuroendocrine tumors (PNET-NF). The best treatment is controversial, some authors advise a conservative approach in selected cases. Our aim is to analyze the evolution of incidental, small size PNET-NF, treated with clinical follow-up without surgery. MethodsWe performed a retrospective analysis of a prospective database of patients diagnosed incidentally with PNET-NF since November 2007 to September 2015. We include those with PNET-NF ≤2cm and asymptomatic. The diagnosis was performed using imaging tests indicating endoscopic ultrasound-guided fine-needle aspiration in case of doubts in the diagnosis. The follow-up was performed at our center, registering clinical and/or radiological changes. ResultsWe included 24 patients with a median age of 70 years, and a similar distribution in terms of sex. The diagnosis was made through computed tomography multidetector or magnetic resonance imaging and octreotide scan. The tumors were located mainly in the head and neck (46%), with a mean size of 11,5±3,55mm at diagnosis (5-19mm). In 2 cases endoscopic ultrasound fine needle aspiration was used (8%), confirming the diagnosis of low-grade PNET with Ki67<5%. The median follow-up was 39 months (7-100). In 19 patients (79%) they remained the same size, 21% (5) increased its size with a mean of 2,6±2mm (1-6). No cases had progression of disease. ConclusionIn selected patients, non-surgical management of PNET-NF is an option to consider, when they are asymptomatic and ≤2cm. Larger studies with more patients and more time of follow-up are needed to validate this non-operative approach.

Surgery management for sporadic small (≤2 cm), non-functioning pancreatic neuroendocrine tumors: a consensus statement by the Chinese Study Group for Neuroendocrine Tumors (CSNET).

The incidence of small (≤2cm), non-functioning pancreatic neuroendocrine tumors (NF-pNETs) increased in the last decades. Before making appropriate strategy for patients with NF-pNETs ≤2cm, pathological confirmation is vital. Incidentally diagnosed, sporadic small NF-pNETs may bring aggressive behavior and poor prognosis, such as extrapancreatic extension, lymph nodal metastasis, distant metastasis and recurrence, even causing disease-related death. Understanding and formulating an appropriate strategy for the patients with sporadic small, non-functioning pancreatic neuroendocrine tumors have been controversial for some time. Although several studies have reported that patients with NF-pNETs ≤2cm had less rate of malignant behavior compared with larger ones (>2 cm); and the surgery approach may leading to surgery-related pancreatic complications; but there is still a lack of levelI evidence to convince surgeons to abandon all cases with sporadic small NF-pNETs. Based on an updated literature search and review, the members of the Chinese Study Group for Neuroendocrine Tumors (CSNET) from high-volume centers have reached a consensus on the issue of the management strategy for the sporadic small NF-pNETs. We recommend that, except for some selected patients with NF-pNETs <1cm, incidentally discovered and unacceptable surgical risks, all others with NF-pNETs ≤2cm should undergo tumor resection with lymph node dissection or at least lymph node sampling and careful postoperative surveillance.

Is the 2-cm size cutoff relevant for small nonfunctioning pancreatic neuroendocrine tumors: A French multicenter study

Nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) are often discovered at a small size. No clear consensus exists on the management of NF-PNETs ≤ 2 cm. The aim of our study was to determine the prognostic value of indicators of malignancy in sporadic NF-PNETs ≤ 2 cm. Eighty patients were evaluated retrospectively in 7 French University Hospital Centers. Patients were managed by operative resection (operative group [OG]) or observational follow-up (non-OG [NOG]). Pathologic characteristics and outcomes were analyzed. Sixty-six patients (58% women) were in the OG (mean age, 59 years; 95% CI, 56.0-62.3; mean tumor size, 1.6 cm; 95% CI, 1.5-1.7); 14 (72% women, n = 10) were in the NOG (mean age, 63 years; 95% CI, 56-70; mean tumor size, 1.4 cm; 95% CI, 1.0-1.7). All PNETs were ranked using the European Neuroendocrine Tumor Society grading system. Fifteen patients (19%) had malignant tumors defined by node or liver metastasis (synchronous or metachronous). The median disease-free survival was different between malignant and nonmalignant PNETs, respectively: 16 (range, 4-72) versus 30 months (range, 1-156; P = .03). On a receiver operating characteristic (ROC) curve, tumor size had a significant impact on malignancy (area under the curve [AUC], 0.75; P = .03), but not Ki-67 (AUC, 0.59; P = .31). A tumor size cutoff was found on the ROC curve at 1.7 cm (odd ratio, 10.8; 95% CI; 2.2-53.2; P = .003) with a sensitivity of 92% and a specificity of 75% to predict malignancy. Based on our retrospective study, the cutoff of 2 cm of malignancy used for small NF-PNETs could be decreased to 1.7 cm to select patients more accurately.

Resection versus expectant management of small incidentally discovered nonfunctional pancreatic neuroendocrine tumors

Sporadic, nonfunctional pancreatic neuroendocrine tumors (NF-PNETs) are diagnosed with increasing frequency. We compared the risk of tumor growth, metastasis, and mortality between patients treated versus those treated expectantly. A retrospective study of patients seen at our institution with sporadic NF-PNETs, with ≥ 12 months of follow-up. Kaplan-Meier analysis was performed. Between 1999 and 2014, 35 patients with an incidentally discovered nonfunctional PNET were identified. Twenty underwent resection and 15 were followed with imaging. In the operative group, 8 had NF-PNETs < 2 cm, while 12 had NF-PNETs ≥ 2 cm. In the nonoperative expectant management by serial imaging group, 10 had NF-PNETs < 2 cm while 5 had NF-PNETs ≥ 2 cm. Small NF-PNETs (<2 cm) in either the operative or nonoperative groups demonstrated no evidence of progression or metastasis (median follow-up of 27.8 months). Morbidity in the operative group was 35% with pancreatic pseudocyst the most common. Incidentally discovered NF-PNETs < 2 cm in size can be observed safely with serial imaging.

Behavior of Small, Asymptomatic, Nonfunctioning Pancreatic Neuroendocrine Tumors (NF-PNETs).

Small nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) usually exhibit minimal or no growth over many years. However, there is a controversy regarding the optimal management of incidentally discovered, small NF-PNETs. This study aimed to gain insights into tumor behavior and potential strategies for clinical management.We retrospectively reviewed a total of 202 patients with a suspected PNET (size 2 cm or smaller) at Samsung Medical Center from January 1, 1995 to April 30, 2012. Among these patients, 72 patients were excluded and 145 patients were enrolled in our study. Patients were included if the size of the tumor was ≤2 cm without familial syndrome, radiographic evidence of local invasion or metastases.Among the 145 patients, 76 patients (52.4%) had pathologically confirmed PNETs. Eleven (14.5%) and 3 (3.9%) of these 76 patients were diagnosed with NET G2 and G3, respectively. PNETs measuring 1.5 cm or more in size had a higher probability of being classified as NET G2 or G3 compared with PNETs measuring <1.5 cm (P = 0.03). Older age (≥55 years) and a meaningful tumor growth (≥20% or ≥5 mm) were significantly associated with NET G2 or G3 (P < 0.05).Older age (≥55 years), larger tumor size (≥1.5 cm), and a meaningful tumor growth (≥20% or ≥5 mm) were associated with NET G2 or G3. Intensive follow-up could be an acceptable approach in small (especially <1.5 cm), asymptomatic, NF-PNETs.

Outcomes of resected nonfunctional pancreatic neuroendocrine tumors: Do size and symptoms matter?

Nonfunctional pancreatic neuroendocrine tumors (NF-PNETs) are rare tumors with highly variable outcome. Current guidelines recommend surveillance for small tumors (≤ 2 cm), but a scientific basis for such recommendation is scarce. Patients who underwent surgery for NF-PNET during 2001-2013 were identified from a prospectively maintained database and reviewed retrospectively. Fifty-eight patients that had undergone an operative procedure for NF-PNET were identified. Forty-one patients (71%) were symptomatic. Median size of the tumor was 2.5 cm (range 0.9-12.0 cm). WHO 2010 grade was predictive of both overall- and disease-free survival (P < .001), whereas size alone was not. Twenty-four patients had a small NF-PNET (≤ 2 cm), of whom 16 were symptomatic and 8 asymptomatic. Seven patients with small symptomatic NF-PNETs showed signs of malignant behavior: 4 had lymph node metastases, 1 had liver metastases before surgery, 3 developed liver metastases, and 3 died of the disease. All 7 patients had either bile duct or pancreatic duct obstruction or both on preoperative imaging. On the contrary, patients with small asymptomatic NF-PNETs did not develop distant metastases nor died of disease. The 2010 grading system from the World Health Organization can be used to predict survival. Symptomatic small NF-PNETs that caused bile and/or pancreatic duct obstruction had poor outcome. In contrast, asymptomatic small NF-PNETs seem to have benign course, and are candidates for surveillance.

Circulating immune cells in patients with surgically resected nonfunctional pancreatic neuroendocrine tumors

Meeting abstracts There is debate regarding whether surgical resection and/or lymphadenectomy are indicated for small nonfunctional pancreatic neuroendocrine tumors (PNETs). Myeloid cell population expansion in peripheral blood has been correlated with clinical stage of patients with solid tumors.