Portal vein resection in pancreatic neuroendocrine neoplasms.

BACKGROUND: Surgery offers the only cure for borderline resectable or locally advanced pancreatic neuroendocrine neoplasms. Data on incidence, perioperative and long-term outcomes of portal vein resection for pancreatic neuroendocrine neoplasms are scarce. This study aimed to analyze the outcome and prognostic factors of portal vein resection in surgery for pancreatic neuroendocrine neoplasms. METHODS: Consecutive patients were analyzed. Portal vein resection was classified according to the International Study Group of Pancreatic Surgery. Clinicopathologic features and overall and disease-free survival were assessed and compared with standard resection in a matched-pair analysis. RESULTS: A total of 54 of 666 (8%) resected pancreatic neuroendocrine neoplasms patients underwent portal vein resection, including 7 (13%) tangential resections with venorrhaphy (type 1), 2 (4%) patch reconstructions (type 2), 35 (65%) end-to-end anastomoses (type 3), and 10 (19%) graft interpositions (type 4); 52% of those underwent pancreatoduodenectomy, 22% distal pancreatectomy, and 26% total pancreatectomy. Postoperative portal vein thrombosis occurred in 19%. Postoperative pancreatic fistula grades B and C (9% vs 16%; P = .357), complications Clavien-Dindo grade ≥IIIb (28% vs 13%; P = .071), and 90-day mortality rate (2% each) were not significantly different compared with 108 matched patients. The 5-year overall survival was 45% (standard resection: 68%; P = .432), and the 5-year disease-free survival was 25% (standard resection: 34%; P = .716). Radical resection was associated with 5-year overall survival of 51% and 5-year disease-specific survival of 75%. CONCLUSION: This is the largest single-center analysis evaluating perioperative and long-term outcomes of portal vein resection for pancreatic neuroendocrine neoplasms. The postoperative complication rate after portal vein resection is comparable with standard resection. The 90-day mortality is low. Radical resection leads to excellent 5-year oncological survival.

Lymph node metastases and recurrence in pancreatic neuroendocrine neoplasms.

BACKGROUND: The impact of lymph node metastasis on survival in pancreatic neuroendocrine neoplasms as well as their best surgical treatment is controversial. We aimed to determine the frequency and prognostic impact of lymph node involvement in pancreatic neuroendocrine neoplasms. METHODS: Patients undergoing pancreatic resections for pancreatic neuroendocrine neoplasms between 2001 and 2019 were retrospectively analyzed based on a prospective database. Clinicopathological parameters and perioperative outcome were assessed. Overall and disease-free survival was analyzed. Subgroup analysis was performed for sporadic, nonfunctional pancreatic neuroendocrine neoplasms without distant metastases and ≥4 analyzed lymph nodes. RESULTS: Of 605 surgically resected pancreatic neuroendocrine neoplasms, 55% were G1, 36% were G2, and 9% were G3 differentiated. At the time of resection, 34% of patients had lymph node metastasis, and 16% had distant metastases. For subgroup analysis, 314 patients were analyzed. Lymph node metastases occurred in 36% of patients and were most frequent in G3 patients (67%). An increase in tumor size and advancement was associated with higher rates of lymph node metastasis, and disease-free survival was significantly impaired. Significant differences in disease-free survival were observed between 1 and 3 (5-year disease-free survival 52%) and ≥4 positive lymph nodes (5-year disease-free survival 28%), as well as when G3 tumors were excluded. In multivariable analysis, grading, tumor stage, and especially lymph node metastases as well as the proposed pN1 and pN2 categories were confirmed as independent predictors of recurrence. CONCLUSION: The presence and extent of lymph node involvement has considerable prognostic impact in pancreatic neuroendocrine neoplasms. This study, for the first time, validated the proposed pN2 stage for well-differentiated pancreatic neuroendocrine neoplasms.

Enucleation Is a Feasible Procedure for Well-Differentiated pNEN-A Matched Pair Analysis.

The extent of surgical resection in the treatment of pancreatic neuroendocrine neoplasms (pNEN) is still controversial. This study aimed to evaluate the outcomes of enucleation for well-differentiated non-functional (nf) pNEN. Patients undergoing enucleation (2001−2020) were analyzed. Clinicopathological parameters, perioperative outcomes and survival were assessed. The analysis was performed as a nested case-control study and matched-pair analysis with formal resection. Sixty-one patients undergoing enucleation were identified. Compared to patients undergoing formal resection, enucleation was associated with a significantly shorter median length of operative time (128 (IQR 95−170) versus 263 (172−337) minutes, p < 0.0001) and a significantly lower rate of postoperative diabetes (2% versus 21%, p = 0.0020). There was no significant difference in postoperative pancreatic fistula rate (18% versus 16% type B/C, p = 1.0), Clavien−Dindo ≥ III complications (20% versus 26%, p = 0.5189), readmission rate (12% versus 15%, p = 0.6022) or length of hospital stay (8 (7−11) versus 10 (8−17) days, p = 0.0652). There was no 30-day mortality after enucleation compared to 1.6% (n = 1) after formal resection. 10-year overall survival (OS) and disease-free survival (DFS) was similar between the two groups (OS: 89% versus 77%, p = 0.2756; DFS: 98% versus 91%, p = 0.0873). Enucleation presents a safe surgical approach for well-differentiated nf-pNEN with good long-term outcomes for selected patients.

C-reactive protein independently predicts survival in pancreatic neuroendocrine neoplasms.

Pancreatic neuroendocrine neoplasms (pNEN) are highly variable in their postresection survival. Determination of preoperative risk factors is essential for treatment strategies. C-reactive protein (CRP) has been implicated in the pathogenesis of pNEN and shown to be associated with survival in different tumour entities. Patients undergoing surgery for pNEN were retrospectively analysed. Patients were divided into three subgroups according to preoperative CRP serum levels. Clinicopathological features, overall and disease-free survival were assessed. Uni- and multivariable survival analyses were performed. 517 surgically resected pNEN patients were analysed. CRP levels were significantly associated with relevant clinicopathological parameters and prognosis and were able to stratify subgroups with significant and clinically relevant differences in overall and disease-free survival. In univariable sensitivity analyses CRP was confirmed as a prognostic factor for overall survival in subgroups with G2 differentiation, T1/T2 and T3/T4 tumour stages, patients with node positive disease and with and without distant metastases. By multivariable analysis, preoperative CRP was confirmed as an independent predictor of postresection survival together with patient age and the established postoperative pathological predictors grading, T-stage and metastases. Preoperative serum CRP is a strong predictive biomarker for both overall and disease free survival of surgically resected pNEN. CRP is associated with prognosis independently of grading and tumour stage and may be of additional use for treatment decisions.

Pre-operative dysglycemia is associated with decreased survival in patients with pancreatic neuroendocrine neoplasms.

BACKGROUND: Diabetes mellitus is associated with increased risk of pancreatic cancer and impaired postresection survival. For pancreatic neuroendocrine neoplasms, no evidence is available for a similar effect of diabetes mellitus. The aim of this study was to evaluate the glycemic profile in patients with pancreatic neuroendocrine neoplasms and to assess the potential impact of glycemic control on the pathology and long-term outcomes in patients undergoing resection of pancreatic neuroendocrine neoplasms. METHODS: Pancreatic resections from 2001 to 2017 for pancreatic neuroendocrine neoplasms were analyzed from prospective databases. Blood glucose and HbA1c levels were collected from preoperative tests. Preoperative dysglycemia was defined as a blood glucose ≥140 mg% and/or HbA1c ≥6.5%. Uni- and multivariate analyses were performed according to the presence of perioperative dysglycemia. Survival analyses were performed by Kaplan-Meier curves and Cox-proportional hazards method. RESULTS: Four hundred and seventeen patients were analyzed. Medical history was positive for diabetes mellitus in 88 (21.1%) patients. Blood glucose evaluation identified 30 additional patients without a prior diagnosis of diabetes mellitus who had preoperative dysglycemia. No differences regarding pathologic characteristics or outcomes were detected between diabetics and non-diabetics. Conversely, patients with dysglycemia had greater rates of metastasis (16.8% vs 27.4%; P = .027) as well as vascular, perineural, and lympho-vascular involvement than those with normal blood glucose (89.2% vs 57.4%; P < .001, 90.0% vs 65.1%; P = .046, and 89.3% vs 61.3; P = .006, respectively). Preoperative dysglycemia was associated with impaired overall survival (hazard ratio = 1.57 [1.01-2.46]) and recurrence-free survival (hazard ratio = 1.78 [1.01-3.12]). By multivariate analysis, preoperative dysglycemia was independently associated with recurrence-free survival (hazard ratio 2.32 [1.29-4.17]), together with lymph-node involvement (hazard ratio = 2.01 [1.14-3.57]) and metastatic disease (hazard ratio = 5.10 [2.73-9.55]). CONCLUSION: Preoperative dysglycemia, but not diabetes mellitus per se, is associated with advanced disease and impaired long-term outcomes in patients undergoing resection for a pancreatic neuroendocrine neoplasm. For those patients, closer surveillance and strict glycemic control are warranted.