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Introduction: To investigate the impact of prognostic nutritional index (PNI) on short- and long-term outcomes of patients who underwent curative-intent resection for gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs). Methods: Patients with GET-NETs who underwent curative-intent resection were identified from a multi-center database. The prognostic impact of clinicopathological factors including PNI on post-operative outcomes were evaluated. A novel nomogram was developed and externally validated. Results: A total of 2,099 patients with GEP-NETs were included in the training cohort; 255 patients were in the external validation cohort. Median PNI (n = 973) was 47.4 (IQR 43.1–52.4). At the time of presentation, 1,299 (61.9%) patients presented with some type of clinical symptom. Low-PNI (≤42.2) was associated with gastrointestinal symptoms, as well as nodal metastasis and distant metastasis (all p < 0.05). Patients with a low PNI had a higher incidence of severe (≥Clavien-Dindo grade IIIa: low PNI 24.9% vs. high PNI 15.4%, p = 0.001) and multiple (≥3 types of complications: low PNI 14.5% vs. high PNI 9.2%, p = 0.024) complications, as well as a worse overall survival (OS)(5-year OS, low PNI 73.7% vs. high PNI 88.5%, p < 0.001), and RFS (5-year RFS, low PNI 68.5% vs. high PNI 79.8%, p = 0.008) versus patients with high PNI (>42.2). A nomogram based on PNI, tumor grade and metastatic disease demonstrated excellent discrimination and calibration to predict OS in both the training (C-index 0.748) and two external validation (C-index 0.827, 0.745) cohorts. Conclusions: Low PNI was common and associated with worse short- and long-term outcomes among patients with GEP-NETs. [ABSTRACT FROM AUTHOR]

Background: Simple ileocecectomy and right hemicolectomy are two potential operative approaches to treat patients with neuroendocrine neoplasm in the terminal ileum and/or cecum (IC-NENs). We sought to define the long-term outcome of patients undergoing ileocecectomy versus right hemicolectomy for IC-NENs, as well as characterize number of nodes evaluated and lymph node metastasis (LNM) associated with each procedure. Methods: Patients who underwent curative-intent resections for IC-NENs between 2000 and 2016 were identified from a multi-institutional database. The clinicopathologic characteristics, surgical procedures, and the overall (OS) and recurrence-free survival (RFS) were compared among patients who underwent formal right hemicolectomy versus ileocecectomy only. Results: Among 127 patients with IC-NENs, median size of the largest tumor size was 2.0 (IQR 1.2–2.9) cm; 35 (27.6%) patients had multiple lesions. At the time of surgery, 93 (73.2%) patients underwent a right hemicolectomy, whereas 34 (26.8%) had ileocecectomy only. Every patient had a lymph node dissection (LND) with a median number of 16 (IQR 12–22) nodes evaluated. A majority (n = 110, 86.6%) of patients had LNM with a median number of 3 (IQR 2–5) LNM. Patients who underwent hemicolectomy had more lymph nodes evaluated versus patients who had an ileocecectomy only (median, 18 vs. 14, p = 0.004). Patients who underwent formal right hemicolectomy versus ileocecectomy had a similar OS (median OS, 101.9 vs. 144.5 months, p = 0.44) and RFS (median RFS, 70.3 vs. not attained, p = 0.80), respectively. Conclusions: Ileocecectomy had similar long-term outcomes versus right hemicolectomy in treatment of IC-NENs despite a difference in the lymph node harvest. [ABSTRACT FROM AUTHOR]

Background: Patients can experience recurrence following curative-intent resection of non-functional pancreatic neuroendocrine tumors (NF-pNETs). We sought to develop a nomogram to risk stratify patients relative to recurrence following resection of NF-pNETs. Methods: Patients who underwent curative-intent resection for NF-pNETs between 1997 and 2016 were identified from a multi-institutional database. The impact of clinicopathologic factors, including tumor burden score (TBS) (TBS2 = (maximum tumor diameter)2 + (number of tumors)2), was assessed relative to recurrence-free survival (RFS), and a nomogram was developed and internally validated. Results: With a median follow-up of 31.0 months (IQR 11.3–56.6 months), 66 (15.8%) out of 416 patients in the cohort experienced tumor recurrence. Overall, 3-, 5-, and 10-year RFS following curative-intent resection was 83.2%, 74.0%, and 44.7%, respectively. Several factors were associated with risk of recurrence including tumor grade (referent G1: G2, HR 4.07, 95% CI 2.29–7.26, p < 0.001; G3, HR 10.83, 95% CI 3.72–31.53, p < 0.001), lymph node metastasis (LNM) (HR 4.71, 95% CI 2.69–8.26, p < 0.001), as well as TBS (referent low: medium, HR 4.36, 95% CI 2.06–9.24, p < 0.001; high, HR 6.04, 95% CI 2.96–12.31, p < 0.001). A weighted nomogram including tumor grade (G1 0, G2 54.19, G3 100), LNM (N0 0, N1 42.06), and TBS (low 0, medium 44.07, high 56.48) was developed. The discriminatory power of the nomogram was very good with a C-index of 0.75 (95% CI, 0.66–0.79) in the training cohort and 0.71 (95% CI, 0.65–0.75) in the validation cohort. In addition, the nomogram performed better than the current 8th edition of AJCC TNM staging system, which had a C-index of 0.67 (95% CI, 0.60–0.73). Conclusions: A nomogram that incorporated tumor grade, LNM, and TBS was established that had good discrimination and calibration. The nomogram may be an effective tool to stratify patients relative to recurrence risk following resection of NF-pNETs. [ABSTRACT FROM AUTHOR]

Pancreatoduodenectomy (PD) or distal pancreatectomy (DP) are common procedures for patients with a pancreatic neuroendocrine tumor (pNET). Nevertheless, certain patients may benefit from a pancreas-preserving resection such as enucleation (EN). The aim of this study was to define the indications and differences in long-term outcomes among patients undergoing EN and PD/DP. Patients undergoing resection of a pNET between 1992 and 2016 were identified. Indications and outcomes were evaluated, and propensity score matching (PSM) analysis was performed to compare long-term outcomes between patients who underwent EN versus PD/DP. Among 1034 patients, 143 (13.8%) underwent EN, 304 (29.4%) PD, and 587 (56.8%) DP. Indications for EN were small size (1.5 cm, IQR:1.0–1.9), functional tumors (58.0%) that were mainly insulinomas (51.7%). After PSM (n = 109 per group), incidence of postoperative pancreatic fistula (POPF) grade B/C was higher after EN (24.5%) compared with PD/DP (14.0%) (p = 0.049). Median recurrence-free survival (RFS) was comparable among patients who underwent EN (47 months, 95% CI:23–71) versus PD/DP (37 months, 95% CI: 33–47, p = 0.480). Comparable long-term outcomes were noted among patients who underwent EN versus PD/DP for pNET. The incidence of clinically significant POPF was higher after EN. [ABSTRACT FROM AUTHOR]

To investigate the feasibility of Tumor Burden Score (TBS) to predict tumor recurrence following curative-intent resection of non-functional pancreatic neuroendocrine tumors (NF-pNETs). The TBS cut-off values were determined by a statistical tool, X-tile. The influence of TBS on recurrence-free survival (RFS) was examined. Among 842 NF-pNETs patients, there was an incremental worsening of RFS as the TBS increased (5-year RFS, low, medium, and high TBS: 92.0%, 73.3%, and 59.3%, respectively; P < 0.001). TBS (AUC 0.74) out-performed both maximum tumor size (AUC 0.65) and number of tumors (AUC 0.5) to predict RFS (TBS vs. maximum tumor size, p = 0.05; TBS vs. number of tumors, p < 0.01). The impact of margin (low TBS: R0 80.4% vs. R1 71.9%, p = 0.01 vs. medium TBS: R0 55.8% vs. R1 37.5%, p = 0.67 vs. high TBS: R0 31.9% vs. R1 12.0%, p = 0.11) and nodal (5-year RFS, low TBS: N0 94.9% vs. N1 68.4%, p < 0.01 vs. medium TBS: N0 81.8% vs. N1 55.4%, p < 0.01 vs. high TBS: N0 58.0% vs. N1 54.2%, p = 0.15) status on 5-year RFS outcomes disappeared among patients who had higher TBS. TBS was strongly associated with risk of recurrence and outperformed both tumor size and number alone. [ABSTRACT FROM AUTHOR]

To define recurrence patterns and time course, as well as risk factors associated with recurrence following curative resection of pNETs. Patients who underwent curative-intent resection for pNET between 1997 and 2016 were identified from the US Neuroendocrine Tumor Study Group. Data on baseline and tumor-specific characteristics, overall survival (OS), timing and first-site of recurrence, predictors and recurrence management were analyzed. Among 1020 patients, 154 (15.1%) patients developed recurrence. Among patients who experienced recurrence, 76 (49.4%) had liver-only recurrence, while 35 (22.7%) had pancreas-only recurrence. The proportion of liver-only recurrence increased from 54.3% within one-year after surgery to 61.5% from four-to-six years after surgery; whereas the proportion of pancreas-only recurrence decreased from 26.1% to 7.7% over these time periods. While liver-only recurrence was associated with tumor characteristics, pancreas-only recurrence was only associated with surgical margin status. Patients undergoing curative resection of recurrence had comparable OS with patients who had no recurrence (median OS, pancreas-only recurrence, 133.9 months; liver-only recurrence, not attained; no recurrence, 143.0 months, p = 0.499) Different recurrence patterns and timing course, as well as risk factors suggest biological heterogeneity of pNET recurrence. A personalized approach to postoperative surveillance and treatment of recurrence disease should be considered. [ABSTRACT FROM AUTHOR]

Background: The effect of diabetes on survival after resection pancreatic ductal carcinoma (PDAC) is unclear. The present study was undertaken to determine whether pre-operative diabetes has any predictive value for survival. Methods: A retrospective review from seven centres was performed. Metabolic factors, tumour characteristics and outcomes of patients undergoing resection for PDAC were collected. Univariate and multivariable analyses were performed to determine factors associated with disease-free (DFS) and overall survival (OS). Results: Of the 509 patients in the present study, 31.2% had diabetes. Scoring systems were devised to predict OS and DFS based on a training set ( n= 245) and were subsequently tested on an independent set ( n= 264). Pre-operative diabetes ( P < 0.001), tumour size >2 cm ( P= 0.001), metastatic nodal ratio >0.1 ( P < 0.001) and R1 margin ( P < 0.001) all correlated with DFS and OS on univariate analysis. Scoring systems were devised based on multivariable analysis of the above factors. Diabetes and the metastatic nodal ratio were the most important factors in each system, earning two points for OS and four points for DFS. These scoring systems significantly correlated with both DFS ( P < 0.001) and OS ( P < 0.001). Conclusion: Pre-operative diabetes status provides useful information that can help to stratify patients in terms of predicted post-operative OS and DFS. [ABSTRACT FROM AUTHOR]