One hundred twenty-two patients had operations for PNET; 62 underwent pancreatic enucleation and 60 underwent pancreatic resection. The median age at the time of surgery was 42 years (range 11–78 years) with a slight female predominance 58.2 % (71/122). The patients had a median body mass index (BMI) of 28.7 kg/m2 and a preoperative serum albumin level of 3.9 g/dL. Some 52.5 % (64/122) of the patients had an inherited genetic disease, and 63.1 % (77/122) had functional tumors (). There were 28 patients with MEN-1, 34 with VHL, one with neurofibromatosis (NF), and one with Birt–Hogg–Dubé syndrome. Our study had 53 insulinomas, 16 gastrinomas, one VIPoma, one somatostatinoma; one corticotropin releasing hormone (CRH) producing lesion, one adrenocorticotropic hormone (ACTH) producing lesion, one luteinizing hormone (LH) producing lesion, and one ectopic pheochromocytoma; one accessory spleen in a patient with a history of prior PNET; one pancreatic acinar carcinoma in a patient with VHL; and two microcystic adenomas in patients with VHL. There were 43 patients with nonfunctional PNET ().
Demographics and clinical characteristics of study cohort
Types of pancreatic neuroendocrine tumors (PNET)
The pancreatic enucleation and resection group were analyzed separately with the ISGPF criteria for POPF [3
] (). The postsurgical outcomes data used to classify patients based on ISGPF criteria are shown in (). The 30 day mortality was less than 1 % (1/122 patients), and 6.6 % (8/122 patients) required a reoperation.
Pancreatic fistula grade criteria suggested by Study Group of Pancreatic Fistula (IGSPF)
The 62 patients underwent pancreatic enucleation of 83 lesions. During a single procedure, 51 patients had one enucleation, 3 patients had two enucleations, 7 patients had three enucleations, and 1 patient had more than five lesions enucleated. Nine patients underwent a laparoscopic procedure and 53 patients underwent a laparotomy. The largest lesion was enucleated from the head of the pancreas in 42 patients and from the body or tail of the pancreas in 20 other patients (). The median size of the largest lesion enucleated was 1.8 ± 0.74 cm.
Sixty patients underwent a pancreatic resection for their PNET. Thirteen patients underwent a laparoscopic procedure and 47 underwent a laparotomy. These patients received a variety of pancreatic resections, including 39 distal pancreatectomy, 15 pancreaticoduodenectomy, 3 subtotal pancreatectomy, 1 total pancreatectomy, 2 pancreaticoduodenectomy and distal pancreatectomy. Of these 60 patients, 2 patients had simultaneous pancreaticoduodenectomy and distal pancreatectomy and 10 had a combined pancreatectomy and enucleation (). The median size of the largest lesion resected was 3.2 ± 2.5 cm.
In the enucleation group, the POPF were graded as follows: 25.8 % (16/62) grade A, 14.5 % (9/62) grade B1, 22.6 % (14/62) grade B2, and 4.8 % (3/62) grade C. Grade B and C POPF was found in 26 of 62 patients. Clinically significant POPF occurred in 14 patients with grade B2 and 3 patients with grade C, for a total rate of 27.4 % (17/62) (). A univariate analysis was done evaluating age, gender, albumin, BMI, type of procedure, number of lesions, size of largest lesion, location of lesion, histology, functionality of PNET, and inherited genetic diseases. Non-insulinoma tumors (p = 0.02) and inherited genetic diseases (p = 0.02) were associated with a higher POPF rate (). Based on the p <0.10 threshold for evaluating parameters in a multivariate logistic model, histology, number of lesions, and inherited genetic disease type were considered as variables to be potentially evaluated relative to their association with development of a fistula. With a backward selection algorithm, it was determined that only inherited genetic diseases would be associated with fistula. This model was able to correctly classify 17/20 (85 %) patients without a fistula but only 20/42 with a fistula (48 %). Most patients (38/40) with insulinoma were sporadic, whereas almost all patients (21/22) with non-insulinoma tumors had an inherited disease and had a 1.5 times higher rate of POPF.
Univariate analysis of factors associated with postoperative pancreatic fistula (POPF)
For the pancreatic resection group, the POPF were graded: 18.3 % (11/60) grade A, 18.3 % (11/60) grade B1, 16.7 % (10/60) grade B2, and 3.3 % (2/60) grade C. Grade B and C POPF was found in 23 of 60 patients. Clinically significant POPF occurred in 10 patients with grade B2 and 2 patients with gade C, for a total rate of 20 % (12/60 patients) (). A univariate analysis was conducted evaluating age, gender, albumin, BMI, transfusion, type of procedure, number of lesions, size of largest lesion, histology, functionality of PNET, and inherited genetic diseases. A BMI >25 (p <0.01), MEN-1 (p <0.01), and combined pancreatic resections and enucleation or simultaneous pancreaticoduodenectomy and distal pancreatectomy (p = 0.02) were associated with a higher POPF rate (). Those with a fistula also tended to have greater maximal lesion size (mean ± SEM = 3.75 ± 0.53 vs. 2.40 ± 0.20; p = 0.067), as well as larger actual BMI (31.79 ± 1.38 vs. 26.44 ± 1.01; p = 0.011). Using the p = 0.10 threshold from the screening procedure to determine which parameters to include in a multivariate logistic regression model, BMI, MEN-1 or not, VHL or not, extent of surgery (combined pancreatic resections and enucleation or simultaneous pancreaticoduodenectomy and distal pancreatectomy), and maximum lesion size were all considered for inclusion in such a model. Based on a backward selection algorithm, a model with actual maximal lesion size and whether BMI was normal or not could be used to predict who would or would not have a fistula in the resection group.
Specifically, the model resulted in the following classification rule:
Applying these rules to the data from which they were derived results in the following classification: 16/22 (68 %) without a fistula would be correctly identified, whereas 20/32 (63 %) with a fistula would be correctly identified. Further analysis of each surgical subgroup (enucleation and resection) was performed to identify if any surgical, clinical, or pathologic factors were predictive of severity of POPF. Risk factors were associated with the development of POPF but did not correlate with severity (grade A, B, or C) of fistula that developed. If patients who underwent combined procedures are excluded from the pancreatic resection group, there is still no difference in POPF between the groups. The POPF rate is 23 of 48 in the resection group and 26 of 62 in the enucleation group (p = 0.57).
Our clinically significant POPF rate for all procedures performed on PNET was 23.7 % (29/122). In the 122 patients, we identified 24 (16.4 %) grade B2 fistulas (14 enucleations and 10 resections) and 5 (4.1 %) grade C fistulas (3 enucleations and 2 resections). Patients who underwent pancreatic enucleation had a clinically significant POPF rate of 27.4 % (17/62), and those who underwent pancreatic resection had a POPF rate of 20 % (12/60). The difference in POPF was not significant (p = 0.4). Patient characteristics were analyzed separately by type of operation (resection vs. enucleation) ().