Resection Of Pancreatic Neuroendocrine Tumors Research Articles

18F-FDG PET/CT Volumetric Parameters are Associated with Tumor Grade and Metastasis in Pancreatic Neuroendocrine Tumors in von Hippel-Lindau Disease.

Approximately 8-17% of patients with von Hippel-Lindau (VHL) syndrome develop pancreatic neuroendocrine tumors (PNETs), with 11-20% developing metastases. Tumor grade is predictive of prognosis. The aim of this study was to determine if preoperative metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were associated with metastatic disease and tumor grade. Sixty-two patients with VHL-associated PNETs prospectively underwent 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT). MTV, TLG, and maximum standardized uptake value (SUVmax) were measured using a semi-automatic method. Surgically resected PNETs were classified according to 2010 World Health Organization tumor grade classification. MTV, TLG, and SUVmax were analyzed by metastatic disease and tumor grade using the Mann-Whitney test. A total of 88 PNETs were identified by CT and 18F-FDG PET/CT, 10 of which were non-FDG-avid. Histologic grading was available for 20 surgical patients. Patients with metastatic PNETs had a higher TLG (median 25.9 vs. 7.7 mean SUV [SUVmean]*mL; p=0.0092) compared with patients without metastasis, while patients with grade 2 PNETs had a higher MTV (median 6.9 vs. 2.6mL; p=0.034) and TLG (median 41.2 vs. 13.1 SUVmean*mL; p=0.0035) compared with patients with grade 1 PNETs. No difference in tumor size or SUVmax was observed between the groups. Patients with metastatic PNETs have a higher TLG compared with patients without metastasis. Grade 2 PNETs have a higher MTV and TLG compared with grade 1 PNETs. Tumor size and SUVmax were not associated with grade. Volumetric parameters on 18F-FDG PET/CT may be useful in detecting higher grade PNETs with a higher malignant potential that may need surgical intervention.

Consensus on determinants of tumor resection of pancreatic neuroendocrine tumors

Consensus on determinants of tumor resection of pancreatic neuroendocrine tumors

Factores pronósticos de los tumores neuroendocrinos de páncreas resecados. Experiencia en 95 pacientes

IntroductionThe aim of this study was to analyze prognostic factors for survival and recurrence in patients with resected pancreatic neuroendocrine tumors (PNT). MethodsMedical records of 95 patients with resected PNT were retrospectively reviewed. The variables studied were: age, sex, form of presentation (sporadic/familial tumors), functionality, type of tumor, localization, type of surgery, tumor size, multifocal tumors and recurrent rate. The new WHO classification (2010) was used. ResultsThere were 45 men and 50 women. Mean age was 46.8 years. Regarding the mode of presentation, it was sporadic in 66 patients (69.8%) and 29 cases were familial neuroendocrine tumors (30.2%) in association with MEN 1 syndrome. The 59% of patients suffered from non-functional tumors and 41% were functional: 20 insulinoma, 16 gastrinoma, and 3 glucagonoma. Distal pancreatectomy was the most common surgical procedure, followed by tumor enucleation in 19 patients. According to the WHO classification, 59 patients had a PNT G1, 24 PNT G2 and 12 with a poorly-differentiated carcinoma, respectively. The 5-year survival in well-differentiated tumors was 100%, regardless of the functionality. Sporadic PNT are more commonly unifocal (P<0.001), associating liver metastasis. Survival and recurrence rates after a mean follow-up of 85.3 months were 65.8 and 24%, respectively. ConclusionsIn our experience, WHO classification was an independent prognostic factor in PNT survival.

Microscopic venous invasion in patients with pancreatic neuroendocrine tumor as a potential predictor of postoperative recurrence

BackgroundMicroscopic venous and lymphatic invasion is a known prognostic factor for various cancers, but its prognostic relevance for pancreatic neuroendocrine tumors (PNETs) is unclear. MethodsThirty-two consecutive patients with PNET who had complete resection were included in this study. Venous and lymphatic invasion was identified on elastic tissue or immunohistochemical staining, and correlated with other clinicopathological factors, including recurrence-free survival. ResultsVenous and lymphatic invasion was identified in nine (28%) and three (9%) patients, respectively. Tumors with venous invasion were of significantly larger size, higher Ki-67 index, and higher mitotic counts. Patients with venous invasion showed significantly worse prognosis than those without venous invasion (P = 0.001). Five of nine patients (56%) with venous invasion had tumor recurrence, while a relapse was found in one case in patients without venous invasion (n = 23). Lymphatic invasion was not correlated with any other clinicopathological parameters including lymph node metastasis and recurrence-free survival. Predictive factors for recurrence in univariate analysis included microscopic venous invasion, tumor size ≥ 20 mm, non-functionality, and WHO grades. In multivariate analysis where WHO grades and microscopic venous invasion were applied, venous invasion remained a significant predictor of poor recurrence-free survival (P = 0.021). ConclusionsMicroscopic venous invasion may serve as a predictive factor for tumor recurrence in patients with resectable PNET. The combination of WHO grades and microscopic venous invasion may assist in the stratification of the patients for risk of tumor recurrence.

Nomogram to predict recurrence after curative resection of pancreatic neuroendocrine tumors

Nomogram to predict recurrence after curative resection of pancreatic neuroendocrine tumors

Analysis of long term outcome and identification of the predictors of recurrence in patients with resectable pancreatic neuroendocrine tumors

It is most probable that during natural copulation the semen of the fowl is ejaculated into a shallow position in the vagina of the hen, but during the commercial application of artificial insemination it is generally considered necessary to evert the distal vagina and deposit semen to a depth of at least 5 cm to produce optimal fertilisation of the succession of eggs laid daily by a female for a week post-insemination. Aspects of the artificial insemination technique in relation to the types of semen that are obtained from the male fowl artificially are re-appraised in relation to their effect on fertility. It was confirmed that a smaller number of spermatozoa (50 × 106) than is normally used in commercial practice (>80 × 106) produced good fertility, even when inseminated within 0.5 cm of the vaginal opening in the cloaca. The results were achieved whether or not glucose was present in the inseminate. When semen was deposited in the cloaca, a better fertilisation rate was obtained if ductus-deferens semen was diluted with transparent fluid, which is produced by tumescent tissue in the cloaca during semen collection. However, the same advantageous effect was shown by dilution with synthetic aqueous fluids with and without glucose. The likely role of transparent fluid during natural copulation is discussed. On the basis of the number of spermatozoa found to maintain good fertility by artificial insemination, only 10 μl semen would be required to be ejaculated into each hen during copulation. This may account for the well-known ability of the male fowl to copulate frequently in a day, because the small volume of semen would be replenished, naturally, very quickly in the ductus deferens.

Nomogram to predict recurrence after curative resection of pancreatic neuroendocrine tumors.

e15654Background: Early stagenon-functioning pancreatic neuroendocrine tumors (NF-pNETs) are diagnosed more often due to improved recognition and imaging. Surgical resection is the preferred treatment, but recurrence still occurs frequently. Aim of this study is to predict recurrence after resection in order to identify patients that are at risk and might benefit from intense follow-up or adjuvant treatment. Methods: Retrospectively patients with curative resection of NF-pNET of two institutions were included. Distant metastasis, hereditary syndromes and grade 3 tumors were excluded. Recurrence was scored, defined as local tumor recurrence or new localization as lymph node- or distant metastasis. Independent predictors were identified with multivariable Cox regression. Based on hazard ratios a nomogram was developed to predict recurrence within 5-years. External validation with a retrospective cohort from a third center was performed using Harrell’s concordance index. Results: A total of 97 patients with ...

Surgical resection for pancreatic neuroendocrine tumors: A single center experience

Surgical resection for pancreatic neuroendocrine tumors: A single center experience

Aggressive surgical resection for pancreatic neuroendocrine tumors

Aggressive surgical resection for pancreatic neuroendocrine tumors

Enucleation versus anatomic resection for pancreatic neuroendocrine tumors: Preoperative factors that predict lymph node metastases to guide operative strategy

Enucleation versus anatomic resection for pancreatic neuroendocrine tumors: Preoperative factors that predict lymph node metastases to guide operative strategy

Outcomes of Pancreaticoduodenectomy for Pancreatic Neuroendocrine Tumors: Are Combined Procedures Justified?

Efficacy and outcomes of resection for pancreatic neuroendocrine tumors (pNET) are well established; specific data on outcomes for pancreaticoduodenectomy (PD), either alone or with combined procedures, are limited. A retrospective review of PDs for pNET (1998–2014) at our institution was conducted. Patients were categorized into standard PD (SPD) alone or combined PD (CPD) defined as patients undergoing concurrent vascular reconstruction or additional organ resection for curative intent. Kaplan-Meier survival analyses were performed. PD for pNET was performed for 95 patients. Tumors were functional in 11 patients (9 %). Twenty-six patients (28 %) underwent CPD. The 30/90-day mortality was 1.1/5.3 % respectively and similar between SPD and CPD (p = 0.61/p = 0.24). Five-year overall survival after PD for pNET was 85.1/71.9 % and similar between SPD/CPD groups (p = 0.17). Recurrence-free and overall survival for low-grade tumors was 74.7/93.9 % at 5 years compared to only 14.8/49.7 % for high-grade tumors (p < 0.001) and not predicted by extent of resection (SPD/CPD, respectively). PD with or without concurrent resection provides an acceptable, perioperative and long-term oncologic, outcome for pNET. CPD is justified treatment modality, particularly for patients with low-grade tumors. The need for combinatorial procedures during PD is not contraindication alone for otherwise resectable patients with pNET.

A new immunohistochemistry prognostic score (IPS) for recurrence and survival in resected pancreatic neuroendocrine tumors (PanNET).

Pancreatic neuroendocrine tumor (PanNET) is a neoplastic entity in which few prognostic factors are well-known. Here, we aimed to evaluate the prognostic significance of N-myc downstream-regulated gen-1 (NDRG-1), O6-methylguanine DNA methyltransferase (MGMT) and Pleckstrin homology-like domain family A member 3 (PHLDA-3) by immunohistochemistry (IHC) and methylation analysis in 92 patients with resected PanNET and follow-up longer than 24 months. In multivariate analyses, ki-67 and our immunohistochemistry prognostic score (IPS-based on MGMT, NDRG-1 and PHLDA-3 IHC expression) were independent prognostic factors for disease-free-survival (DFS), while age and IPS were independent prognostic factors for overall survival (OS). Our IPS could be a useful prognostic biomarker for recurrence and survival in patients following resection for PanNET.

A new immunohistochemistry prognostic score (IPS) for recurrence and survival in pancreatic neuroendocrine tumors (PanNET).

241 Background: We aimed to evaluate the expression and prognostic significance of N-myc downstream-regulated gen-1 (NDRG-1), O6-methylguanine DNA methyltransferase (MGMT) and Pleckstrin homology-like domain family A member 3 (PHLDA-3) by immunohistochemistry (IHC) and methylation analysis in resected pancreatic neuroendocrine tumors (PanNET). Methods: Ninety-two patients with resected primary PanNET and follow-up &gt; 24 months were included in this study. Nuclear staining for MGMT and PHLDA-3 were scored as 0, 1-5%, 6-50% and ≥ 51%; cytoplasmic NDRG-1 staining was scored based on intensity and pattern from 0 to 2. We then grouped IHC scores for MGMT (absent versus any expression); for NDRG-1 (0 versus 1 versus 2) and for PHLDA-3 ( &lt; 50% versus ≥ 51%). Finally, we developed an immunohistochemistry prognostic score (IPS) based on MGMT, NDRG-1 and PHLDA-3 IHC expression to predict disease free survival (DFS) and overall survival (OS). The discriminatory ability of multivariate models combining the IPS and important clinical variables was assessed with Harrel’s c-index (HCI) and a modification of Harrell’s c-index (mHCI). Results: DFS was significantly worse in patients without any expression of MGMT compared with those with any grade of expression (HR: 2.21; 95%CI: 0.97-5.02; p = 0.013), in patients with moderate or high score for NDRG-1 (p = 0.005), and in those with high-expression for PHLDA-3 (HR: 1.94; 95%CI: 1.05,3.6; p = 0.036). A significant difference in OS was observed based on NDRG-1 score (p = 0.013). In multivariate analyses, ki-67 (HR: 2.45; 95% CI: 1.20-5.01; p = 0.01) and IPS (HR: 2.68; 95% CI: 1.60,4.49; p = 0.00018) were independent prognostic factors for DFS, while age (HR: 7.67; 95% CI: 2.14,27.45; p = 0.0017) and IPS (HR: 2.67; 95% CI: 1.11, 6.41; p = 0.03) were independent prognostic factors for OS. HCI for the multivariate DFS and OS models were 0.796 and 0.788, respectively. Conclusions: Our IPS is a useful prognostic biomarker for recurrence and survival in patients following resection for PanNET. Prospective studies are warranted to validate our findings and determine its role for patients’ selection to neo/adjuvant treatments

Prognostic Value of Somatostatin Receptor Subtypes in Pancreatic Neuroendocrine Tumors.

Studies on the expression of somatostatin receptor (SSTR) subtypes in pancreatic neuroendocrine tumors (PNETs) are rare. The aim of this study was to determine the expression of the SSTR subtypes via immunohistochemistry analyses and assess the correlation between SSTR subtype expression and prognosis. We examined 199 patients with PNET who underwent surgical resection between January 1995 and December 2010 at the Asan Medical Center. For all cases, medical records, including demographic data, clinical symptoms, radiological findings, postoperative treatment outcomes, and expression of SSTR subtypes, were carefully reviewed. In total, 162 (81.4%) PNETs expressed more than 1 SSTR subtype. Functioning PNET expressed significantly more SSTR subtypes, compared to nonfunctioning PNET. The SSTR2(+) and SSTR5(+) groups had better prognosis than the SSTR2(-) (P = 0.009) and SSTR5(-) groups (P = 0.03), respectively. In the grade 2 PNET of 2010 World Health Organization classification, the SSTR(+) group had better prognosis than SSTR(-) group. The expression of SSTR 2 and 5 were related with good prognosis of PNET. In World Health Organization grade 2 PNET, the SSTR(+) group had better prognosis than SSTR(-) group. The SSTR expression(+) by immunohistochemistry might be related with good prognosis of the patients with surgically resected PNET.

A single institution's 21-year experience with surgically resected pancreatic neuroendocrine tumors: an analysis of survival and prognostic factors.

Pancreatic neuroendocrine tumors (pNETs) comprise a heterogeneous group of tumors with a varied biological behavior. In the present study, we analyzed the experience of 79 pNETs resected between 1999 and 2014. The pathologic prognostic factors (European Neuroendocrine Tumor Society, ENETS; and AJCC) classification, vascular invasion (VI), proliferation index (ki-67) and the presence of necrosis were retrospectively reviewed. The clinical data of 79 patients with pNETs who underwent surgery were retrospectively analyzed. Mortality rates and Kaplan-Meier estimates were used to evaluate survival over time for pathologic stages, tumor functionality, and vascular invasion. Cox proportional hazards models were used to calculate the hazard ratio regarding ENETS, AJCC staging, sex, tumor functionality and vascular invasion. The male:female ratio was 40:39. Twenty-one patients (26%) had functional tumors and 58 (73.4%) had non-functional tumors, of which 35 (44.3%) were diagnosed incidentally. Seventeen Whipple procedures, 46 distal pancreatectomies (including 26 laparoscopic and 20 open procedures), 8 laparoscopic central pancreatectomies, 1 laparoscopic resection of the uncinated process and 7 enucleations (one laparoscopic) were performed. Vascular invasion and necrosis were observed in 29 of 75 cases (38.6%) and in 16 cases (29%), respectively. The comparison between survivor functions of ENETS staging categories showed statistically significant differences (p = 0.042). Mortality rate was higher in patients with non-functioning tumors compared with hormonally functioning tumors (p = 0.052) and in those with vascular invasion (p = 0.186). In spite of the heterogeneity of pNETs, the ENETS TNM classification efficiently predicts long-term prognosis. The non-functioning tumors and the presence of vascular invasion are associated with poor prognosis.

Significance of preoperative radiographic pancreatic density in predicting pancreatic fistula after surgery for pancreatic neuroendocrine tumors

BackgroundPostoperative pancreatic fistula remains the most severe and worrisome complication after surgery. Predictive preoperative assessment remains challenging. The authors examine the role of pancreatic computed tomography density in predicting postoperative pancreatic fistula after surgery for pancreatic neuroendocrine tumors. MethodsA single institutional retrospective review of pancreatic surgery for neuroendocrine tumors between 1998 and 2010 was conducted. Preoperative contrast-enhanced computed tomography scans were reviewed, with mean region of interest measurements of pancreatic parenchymal density obtained from 10-mm thick axial computed tomography images. ResultsA total of 119 patients were identified: 59 with enucleations and 60 with resections. Decreased preoperative pancreatic density was significantly associated with an increased grade of postoperative pancreatic fistula (P < .01). Subgroup analyses revealed that decreased gland density was associated with increased grade of postoperative pancreatic fistula in the resection (P < .01) but not in the enucleation group (P = .34). ConclusionsA significant association between postoperative pancreatic fistula grade and preoperative pancreatic computed tomography density is observed in patients undergoing resection for pancreatic neuroendocrine tumors.

Somatostatin Receptor SSTR-2a Expression Is a Stronger Predictor for Survival Than Ki-67 in Pancreatic Neuroendocrine Tumors.

Somatostatin receptors (SSTR) are commonly expressed by neuroendocrine tumors. Expression of SSTR-2a and SSTR-5 may impact symptomatic management; however, the impact on survival is unclear. The aim of this study is to correlate SSTR-2a and SSTR-5 expression in pancreatic neuroendocrine tumors (PNETs) with survival.This study is designed to determine the prognostic significance of somatostatin receptors SSTR-2a and SSTR-5 in PNETs.This retrospective cohort study included cases of resected PNETs between 1992 and 2014. Clinical data, histopathology, expression of SSTR and Ki-67 by immunohistochemistry, and long-term survival were analyzed.A total of 99 cases were included in this study. The mean age was 57.8 years (18–87 years) and median tumor size was 25 mm (range 8–160 mm). SSTR-2a and SSTR-5 expression was scored as negative (n = 19, 19.2%; n = 75, 75.8%, respectively) and positive (n = 80, 80.1%; n = 24, 24.2%). The median follow-up was 49 months. SSTR-2a expression was associated with improved overall survival, with cumulative survival rates at 1, 3, and 5 years being 97.5%, 91.5%, and 82.9%, respectively. Univariate analysis demonstrated better survival in SSTR-2a positive patients (log rank P = 0.04). SSTR-5 expression was not associated with survival outcomes (log rank P = 0.94). Multivariate analysis showed that positive SSTR-2a expression is a stronger prognostic indicator for overall survival [Hazard Ratio (HR): 0.2, 95% Confidence interval (CI): 0.1–0.8] compared to high Ki-67 (HR: 0.8, 95% CI: 0.1–5.7).Expression of SSTR-2a is an independent positive prognostic factor for survival in 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.

Novel score to predict outcome in resected pancreatic neuroendocrine tumors (pNET).

4093 Background: MGMT expression can predict response to temozolomide-based treatment. In pNET PHLDA-3 silencing is a common event while the expression of NDRG-1 and its functional role is unknown....

Determinants of surgical resection for pancreatic neuroendocrine tumors.

Pancreatic neuroendocrine tumors (pNETs) include functioning and non-functional tumors. Functioning tumors consist of tumors that produce a variety of hormones and their clinical effects. Therefore, determinants of resection of pNETs should be discussed for each group of tumors. Less than 10% of insulinomas are malignant, therefore more than 90% of the cases can be cured by surgical resection. Lymphadenectomy is generally not necessary in insulinoma operation. If preoperative localization of the insulinoma is completed, enucleation from the pancreatic body or tail, and distal pancreatectomy can be performed safely by laparoscopy. When preoperative localization of a sporadic insulinoma is not confirmed, surgical exploration is needed. Intraoperative localization of a tumor, intraoperative insulin sampling and frozen section are required. The crucial purpose of surgical resection is to control inappropriate insulin secretion by removing all insulinomas. Gastrinomas are usually located in the duodenum or pancreas, which secrete gastrin and cause Zollinger-Ellison syndrome (ZES). Duodenal gastrinomas are usually small, therefore they are not seen on preoperative imaging studies or endoscopic ultrasound, and can be found only at surgery if a duodenotomy is performed. In addition, lymph node metastasis is found in 40-60% of cases. Therefore, the experienced surgeons should direct operation for gastrinomas. Surgical exploration with duodenotomy should be performed at a laparotomy. Other functioning pNETs can occur in the pancreas or in other locations. Curative resection is always recommended whenever possible after optimal symptomatic control of the clinical syndrome by medical treatment. Indications for surgery depend on clinical symptom control, tumor size, location, extent, malignancy and presence of metastasis. A lot of non-functioning pNETs are found incidentally according to the quality improvement of imaging techniques. Localized, small, malignant non-functioning pNETs should be operated on aggressively, while in possibly benign tumors smaller than 2 cm the surgical risk-benefit ratio should be carefully weighted. Surgical liver resection is generally proposed in curative intent to all patients with operable metastases from G1 or G2 pNET. The benefits of surgical resection of liver metastases have been demonstrated in terms of overall survival and quality of life. Complete resection is associated with better long-term survival.