Small Pancreatic Neuroendocrine Tumors Research Articles

Small pancreatic neuroendocrine tumors: Resect or enucleate?

BackgroundThe aim of this analysis is to compare the postoperative outcomes of resection and enucleation of small pancreatic neuroendocrine tumors (PNETs). MethodsThe 2014-17 American College of Surgeons-NSQIP dataset was queried. Patients undergoing pancreatoduodenectomy (N = 297) or distal pancreatectomy (N = 712) for nonfunctional, small PNETs (T1/T2) were compared to 127 patients (11%) who were enucleated. ResultsOperative time (170 vs 261, p < 0.01) and transfusions were less in the enucleation cohort (1.6% vs 6.7% p < 0.01). There was no difference in postoperative pancreatic fistulas, but morbidity was lower in enucleated patients (36.2% vs 48.7% p < 0.01). Fifteen resected patients died postoperatively (1.5%) while all enucleated patients survived (p = 0.058). Mean postoperative length of stay was shorter after enucleation (5.7 vs 7.2 days p < 0.01). ConclusionsEnucleation of PNETs is performed in only 11% of patients, but takes less time, requires fewer transfusions, and is associated with reduced morbidity and shorter length of stay than resection.

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.

S0052 Optimal Management Strategy for Small (&lt;2 cm) Pancreatic Neuroendocrine Tumors - A Systematic Review and Meta-Analysis of Clinical Trials

S0052 Optimal Management Strategy for Small (&lt;2 cm) Pancreatic Neuroendocrine Tumors - A Systematic Review and Meta-Analysis of Clinical Trials

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.

Observation or resection of small hormone-inactive pancreatic neuroendocrine tumors

Observation or resection of small hormone-inactive pancreatic neuroendocrine tumors

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.

Surgical resection of primary tumor is associated with prolonged survival in low-grade pancreatic neuroendocrine tumors

The incidence of pancreatic neuroendocrine tumors (PNETs) is increasing over the past few decades. Surgery for low-grade and small PNETs of less than 2cm and N0M0 is still debated. The purpose of this study is to examine the association between surgical resection and survival in patients with low-grade nonfunctioning PNETs. Patients diagnosed with PNETs between 2004 and 2015 were extracted from SEER. Kaplan-Meier methods and Cox proportional hazard models were used to estimate independent predictors in PNETs patients. A total of 2637 patients (2147 underwent surgical resection and 490 did not undergo surgery) with histologically confirmed low-grade PNETs in this cohort study. Overall survival (OS) and cancer-specific survival (CSS) of patients with surgery was better than those without surgery (log rank test POS<0.001, PCSS<0.001). Multivariate Cox regression analysis showed that surgical status was an independent prognostic factor associated with OS (HR 3.257, 95%CI: 2.635, 4.026) and CSS (HR 3.546, 95%CI: 2.798, 4.493). Subgroup analysis suggested the patients receiving surgery apparently had better OS and CSS regardless of tumor size (all log rank test POS<0.001, all log rank test PCSS<0.001) and SEER stage (all log rank test POS<0.001, all log rank test PCSS<0.001), compared to patients without removal of the primary tumor. Surgical resection of primary tumor may have a significant benefit on survival for patients with low-grade nonfunctioning PNETs. To determine the optimal management, grade, stage and tumor size should be considered comprehensively.

Endoscopic placement of pancreatic stent for “Deep” pancreatic enucleations operative technique and preliminary experience at two high-volume centers

Pancreatic enucleation (PE) is a viable option for the removal of non-malignant pancreatic masses leading to complete preservation of organ function. Nevertheless, PE is associated with substantial rates of post-operative pancreatic fistula (POPF), particularly when the mass is close to the main pancreatic duct (MPD). Preoperative stenting of the MPD may prevent its injury when performing PE. This paper describes a novel technique of "deep" PE preceded by endoscopic stenting of the MPD. From January 2017 to May 2019, patients with small pancreatic neuroendocrine tumors proximal to the MPD were candidates for PE with previous stenting of the MPD at the University of Verona, Italy, and at the UCLA Medical Center, Los Angeles, California. The endoscopic stenting was scheduled either the day before or 3weeks before surgery, depending on the participating institute. Ten patients were included in this pilot study. The endoscopic procedure was successful and well tolerated in all cases. Open, laparoscopic and robotic PE were performed. Seven patients had surgical complications. Among these, six developed a post-operative pancreatic fistula (POPF), but neither grade C fistulas nor disruptions of the MPD were detected. At pathology, a low grade pancreatic neuroendocrine tumor was confirmed in all cases. In the setting of high-volume centers, this procedure is safe, and it is associated with acceptable short-term surgical morbidity. The preoperative stenting of the MPD might extend the surgical indications for PE.

'Deep' enucleation of pancreatic neoplasms following endoscopic main pancreatic duct stenting: Operative technique and preliminary experience at two high-volume centers

Background: pancreatic enucleation (EN) is a viable option for the radical removal of non-malignant pancreatic masses leading to complete preservation of organ function. Nevertheless, EN is associated with substantial rates of post-operative pancreatic fistula (POPF), particularly when the mass is in close proximity to the main pancreatic duct (MPD). Preoperative stenting of the MPD may prevent its injury when performing EN. The present paper describes a novel technique of 'deep' EN preceded by endoscopic stenting of the MPD. Methods: from January 2017 to April 2018, patients with small pancreatic neuroendocrine tumors proximal to the MPD were candidate to EN with previous stenting of the MPD at the Department of General and Pancreatic Surgery of the University of Verona, Italy, and at the Department of Surgical Oncology, UCLA, California. Results: seven patients were included in this pilot study. The median distance between the tumor and the MPD was 4 mm (1-7) at preoperative endoscopic ultrasound (EUS). After EN, four patients (57%) developed grade B POPF and one patient developed biochemical leak (BL). All resected tumors were G1 pancreatic NETs with Ki67 < 2% at pathology. At the 60-day follow-up, no patients had exocrine or endocrine insufficiency. MRI with MRCP revealed the integrity of both the MPD and parenchyma in all cases. Conclusions: the endoscopic procedure was well tolerated and EN was associated with acceptable short-term surgical morbidity and no disruption of the MPD. In the setting of a high-volume centers, this procedure is safe and effective and may extend the surgical indications for EN. Relevant steps of the surgical enucleation

Resection Versus Observation of Small Asymptomatic Nonfunctioning Pancreatic Neuroendocrine Tumors

BackgroundManagement of asymptomatic, nonfunctioning small pancreatic neuroendocrine tumors (PNETs) is controversial because of their overall good prognosis, and the morbidity and mortality associated with pancreatic surgery. Our aim was to compare the outcomes of resection with expectant management of patients with small asymptomatic PNETs. MethodsRetrospective review of patients with nonfunctioning asymptomatic PNETs < 2 cm that underwent resection or expectant management at the Tel-Aviv Medical Center between 2001 and 2018. ResultsForty-four patients with small asymptomatic, biopsy-proven low-grade PNETs with a KI67 proliferative index < 3% were observed for a mean of 52.48 months. Gallium67DOTATOC-PET scan was completed in 32 patients and demonstrated uptake in the pancreatic tumor in 25 (78%). No patient developed systemic metastases. Two patients underwent resection due to tumor growth, and true tumor enlargement was evidenced in final pathology in one of them. Fifty-five patients underwent immediate resection. Significant complications (Clavien–Dindo grade ≥ 3) developed in 10 patients (18%), mostly due to pancreatic leak, and led to one mortality (1.8%). Pathological evaluation revealed lymphovascular invasion in 1 patient, lymph node metastases in none, and a Ki67 index ≥ 3% in 5. No case of tumor recurrence was diagnosed after mean follow-up of 52.8 months. ConclusionsNo patients with asymptomatic low-grade small PNETs treated by expectant management were diagnosed with regional or systemic metastases after a 52.8-month follow-up. Local tumor progression rate was 2.1%. Surgery has excellent long-term outcomes, but it harbors significant morbidity and mortality. Observation can be considered for selected patients with asymptomatic, small, low grade PNETs.

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

The conundrum of < 2-cm pancreatic neuroendocrine tumors: A preoperative risk score to predict lymph node metastases and guide surgical management

BackgroundManagement of <2-cm pancreatic neuroendocrine tumors is controversial. Although often indolent, the oncologic heterogeneity of these tumors particularly related to lymph node metastases poses challenges when deciding between resection versus surveillance. MethodsWe analyzed all patients who underwent resection of primary nonfunctional <2-cm with curative-intent at 8 institutions of the US Neuroendocrine Tumor Study Group from 2000 to 2016. Pancreatic neuroendocrine tumors with poor differentiation and Ki-67 > 20% were excluded. Our primary aim was to create a lymph node risk score that predicted lymph node metastases accurately for <2-cm pancreatic neuroendocrine tumors, utilizing readily available preoperative data. ResultsOf 695 patients with resected pancreatic neuroendocrine tumors, 309 were <2 cm. Of these small pancreatic neuroendocrine tumors, 25% were proximal (head/uncinate), 23% had a Ki-67 > 3%, and only 8% were moderately differentiated. Also, only 9% of all <2-cm pancreatic neuroendocrine tumors were lymph node (+). Indeed lymph node positivity was associated with worse 5-year recurrence-free survival compared with lymph node (–) disease (80% vs 96%; P = .007). Factors known preoperatively to be associated with lymph node metastases were proximal location (odds ratio 4.0; P = .002) and Ki-67 ≥3% (odds ratio 2.7; P = .05). Moderate differentiation was not associated with lymph node (+) disease. Location and Ki-67 were assigned a value weighted by their odds ratio: (distal= 1, proximal= 4, and Ki-67 < 3% = 1 and Ki-67 ≥ 3% = 3), which formed a lymph node risk score ranging 1–7. Scores were categorized into low (1–2), intermediate (3–4), and high (5–7) risk groups. Incidence of lymph node metastases increased progressively based on risk group, with low = 3.2%, intermediate = 13.8%, and high = 20.5%. Only 3.4% of pancreatic neuroendocrine tumors with a Ki-67 < 3% in the distal pancreas were lymph node (+) compared with 21.4% of pancreatic neuroendocrine tumors with a Ki-67 ≥ 3% in the head/uncinate. ConclusionThis simple and novel lymph node risk score utilizes readily available preoperative factors (tumor location and Ki-67) to stratify risk of lymph node metastases accurately s for < 2-cm pancreatic neuroendocrine tumors and may help guide management strategy.

Duodenal neuroendocrine tumors: Somewhere between the pancreas and small bowel?

377 Background: While small sub-2 cm pancreatic neuroendocrine tumors (NETs) are often observed given their indolent behavior, small bowel NETs are routinely resected with a regional lymphadenectomy regardless of size given their malignant potential. Considering this variability, our aim was to define the natural history of duodenal (D-NETs) and determine the role of resection. Secondary aim was to define clinicopathologic factors associated with overall survival (OS) in pts who undergo resection. Methods: All pts in the National Cancer Database (2004-14) diagnosed with non-metastatic, non-functional D-NETs were included. Local resection (LR) was defined as local excision, polypectomy, or excisional biopsy. Anatomic resection (AR) was defined as removal with radical surgery. Tumor size was divided into three categories (&lt; 1 cm, 1-2 cm, ≥ 2 cm). Propensity score weighting analysis was used to create balanced cohorts between resection and no-resection pts; this was maintained in all three size categories. Primary endpoint was OS. Results: Among 5,502 pts, median age was 65 yrs; 52% were male. Median f/u was 51 mos. Median tumor size was 0.8 cm. Resection was performed in 72% (n = 3954) of which 61% were LR and 39% were AR. At least one lymph node (LN) was retrieved in 25% of pts, of which 44% had LN metastasis. 74% had negative margins. Resection and no-resection cohorts were propensity score weighted for age, gender, race, Charlson-Deyo score, and tumor grade, all of which were independently associated with OS on MV Cox regression analysis, thus creating balanced cohorts. Resection was associated with improved median OS compared to no-resection (MNR vs 94 mos, p &lt; 0.01); this persisted for all three size categories (&lt; 1 cm: MNR vs 194 mos; 1-2 cm: MNR vs 56 mos; &gt; 2 cm: MNR vs 90 mos; all p &lt; 0.01). Subset analysis of each size cohort who underwent resection showed that neither type of resection, LN retrieval, LN positivity, or margin status was associated with OS (all p &gt; 0.05). Conclusions: All pts with non-metastatic non-functional D-NETs should be considered for resection regardless of tumor size. Given their lack of prognostic value, the type of resection and extent of LN retrieval should be tailored to the patient’s clinical picture and safety profile.

The size of well differentiated pancreatic neuroendocrine tumors correlates with Ki67 proliferative index and is not associated with age

BackgroundConcerns exist about a conservative management of well-differentiated nonfunctioning small pancreatic neuroendocrine tumors (NF-PanNET) in young patients and when preoperative Ki67 proliferative index is ≥3%. AimTo evaluate an association between age, tumor size and grading in patients with sporadic NF-PanNET who underwent curative resection. MethodsPatients who underwent surgery for sporadic NF-PanNET (excluding G3) were retrospectively analyzed. Linear regression analysis was performed to evaluate a possible correlation between continuous variables, whereas multiple logistic regression analysis was performed for determining predictors of NF-PanNET-G2. ResultsOverall, 235 patients with NF-PanNET-G1/G2 were included. The median largest radiological diameter was 25 mm. Age correlated neither with tumor size (P = 0.675) nor with Ki67 index (P = 0.376). On multivariate linear regression analysis, factors independently associated with Ki67 index were NF-PanNET size (P = 0.031), perineural invasion (P = 0.004), microvascular invasion (P = 0.001) and necrosis (P = 0.009). The most accurate NF-PanNET size for predicting NF-PanNET-G2 was 25 mm. On multivariate analysis, a NF-PanNET size >25 mm was independently associated with the risk of having a PanNET-G2 (P = 0.025). ConclusionNo correlations exist between age and NF-PanNET size or proliferative index. Therefore, an a priori aggressive attitude is not justified in young patients with small NF-PanNET, as a long-life expectancy is probably unlikely to increase the risk of malignant transformation.

Pancreatic non-functioning neuroendocrine tumor and ,lynch syndrome: a new tumor association

Background: Lynch Syndrome (LS) is a autosomal dominant inheritance caused by a mutation in one of the deoxyribonucleic acid mismatch repair genes. Mutations occur most frequently in the MLH1 and MSH2 genes, followed by MSH6 and then finally PMS2. Colorectal carcinoma (CRC) is the most commonly associated neoplasm. But other neoplasm had been associated: endometrium, gastric, ovarian, breast, small intestine, renal, skin, brain and pancreatic adenocarcinoma. However pancreatic neuroendocrine tumor (PNET), were suggested to be associated but with no confirmation to date. Methods: We present a 65 years old woman affected by LS. She had a CRC 20 year ago. Twelve years later had another one in the right colon. At age of 58 an endometrial cancer was resected. A genetic study was performed and discover a MLH1 MMR gene mutation. She had also a low grade ductal carcinoma of breast at the age of 63 with the same gene mutation. A gastroscopy found a duodenal adenocarcinoma. Results: A pancreaticoduodenectomy was performed. Histology reported a duodenal adenocarcinoma T1N0, two PNET, one G1 and another G2. IHC confirmed the lack of expression of MLH1 and PMS2 in all tumor except in the small PNET. Polymerase chain reaction showed instability only in CRC, duodenal and skin tumors. Conclusion: The association of pancreatic NE tumors and LS is now confirmed and its due to the mutation of the MLH1 and PMS2 nuclear proteins. A gastroscopy with duodenal study should be added in the follow-up of theses patients.

Prognostic significance of Chromogranin A in small pancreatic neuroendocrine tumors

The incidence of nonfunctional pancreatic neuroendocrine tumors ≤2cm is rising. The biologic behavior of these tumors is variable; thus, their management remains controversial. Chromogranin A upregulation is a useful diagnostic biomarker of neuroendocrine tumors; however, the prognostic significance of Chromogranin A is unclear. The objective of this study was to determine whether Chromogranin A levels have prognostic value in pancreatic neuroendocrine tumor patients and may help guide management. We evaluated the National Cancer Database over a 10-year period (2004-2013). Patients with pancreatic neuroendocrine tumors measuring ≤2cm, without distant metastases, were identified and categorized as Chromogranin A high (>420ng/mL) or Chromogranin A low (≤420ng/mL), and those lacking data on Chromogranin A levels were excluded from the study. Univariate and multivariate analyses were performed using Cox proportional hazards model. Cut-point determination was performed using the Contal and O'Quigley method. Of the 445 eligible patients, 352 (79%) were Chromogranin A low and 93 (21%) were Chromogranin A high. Median Chromogranin A level was 71ng/mL (interquartile range, 24-294ng/mL). Chromogranin levels were associated with clinical nodal status and grade. Furthermore, on multivariate analysis, Chromogranin A levels (Chromogranin A high versus Chromogranin A low) independently predicted overall survival after controlling for tumor size, grade, clinical nodal status, and academic status of the facility (hazard ratio: 7.90, 95%CI: 2.34-26.69, P = .001). The greatest benefit of surgical resection was noted in patients in the Chromogranin A high subgroup (log-rank P <.001). Serum Chromogranin A levels can be incorporated in surgical decision-making for patients with small pancreatic neuroendocrine tumors. Patients in the Chromogranin A low group can be considered for observation, whereas patients in the Chromogranin A high group should be strongly considered for resection.

Incidental histological diagnosis of small pancreatic neuroendocrine tumors: are we underestimating their incidence?

Background: The annual incidence of pancreatic neuroendocrine tumors (PanNET) has been estimated to be around 0.8/100,000 inhabitants. Aim of the study was to determine the frequency of incidental histological diagnosis of PanNET during pancreatic specimen evaluation for other neoplasms. Method: We retrospectively reviewed 1023 histopathological examinations of pancreatic specimens performed by three different pathologists in 3 high-volume centers in Italy. Preoperative evaluations and surgical procedures were performed directly or under the supervision of a single surgeon. All the cases with a main pathological diagnosis of PanNET were excluded. Results: An incidental associated diagnosis of PanNET was made in 38 specimens (4%). NET was the most frequent (57%) type of associated neoplasm followed by intraductal mucinous neoplasm (IPMN) (16%). Among those 38 cases, 29 (76%) had a largest diameter < 5 mm (microadenoma). 16 out of 38 incidental PanNET were classified as nonfunctioning (42%) whereas other 7 cases (18%) were classified as glucagonomas. A median value Ki67 of 1% was measured in 9 incidental PanNET. Patients with incidental PanNET were significantly older (median age: 69 years versus 65.5 years, P=0.003). There was no association between incidental diagnosis of PanNET and gender, operation, and main histological diagnosis. When excluding microadenomas, the median age between patients with incidental PanNET (n=9) and the remaining patients was no statistically different (median age 64 years versus 65.5 years, P>0.05). Conclusion: The frequency of incidental histological diagnosis of PanNETs is considerably high suggesting that their real incidence is probably underestimated.

Incidental histological diagnosis of small pancreatic neuroendocrine tumours: Are we underestimating their incidence?

Incidental histological diagnosis of small pancreatic neuroendocrine tumours: Are we underestimating their incidence?

Outcomes after endoscopic ultrasound‐guided ethanol‐lipiodol ablation of small pancreatic neuroendocrine tumors

Little is known about the standard care of small (<2 cm in diameter) pancreatic neuroendocrine tumors (PNET). The aim of the present study was to determine the clinical outcomes of small PNET after endoscopic ultrasound (EUS)-guided ethanol-lipiodol ablation (EUS-ELA). In this prospective cohort study, consecutive patients who underwent EUS-ELA for PNET were enrolled and were followed for ≥3 years. Treatment efficacy was the primary outcome measure. In total, 33 patients who had 40 pathologically confirmed PNET (<2 cm in diameter) were enrolled for final analysis. A total of 63 EUS-ELA sessions were successfully carried out (mean, 1.9 sessions per patient, 1.6 sessions per tumor), which included 40 initial sessions and 23 repeated sessions owing to incomplete ablation. Median actual volume of ethanol-lipiodol mixture injected per session was 1.1 mL (IQR 0.8-1.9 mL). Complete ablation was achieved in 24 of 40 tumors (60%) with one (18 tumors, 45%) or two (24 tumors, 60%) sessions of EUS-ELA. Lipiodol retention within tumor had better treatment outcomes (P = 0.004). Rate of procedure-related adverse events was 3.2%. No malignancy or lymph node metastasis was discovered during a median follow up of 42 months (IQR 39-46 months). We found that EUS-ELA was a safe and effective alternative option in the management of PNET <2.0 cm in diameter; 60% of patients achieved complete ablation. Lipiodol retention within tumor may be a useful early predictor of treatment effectiveness. Trial registered at ClinicalTrials.gov (NCT 01902238).

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