Complications After Pancreatectomy for Neuroendocrine Tumors: A National Study

doi:10.1016/j.jss.2010.04.017

Journal of Surgical Research

Volume 163, Issue 1, September 2010, Pages 63-68

https://doi.org/10.1016/j.jss.2010.04.017 Get rights and content

Background

Although resection of pancreatic neuroendocrine tumors (PNETs) has a demonstrated survival advantage, further evaluation of the overall morbidity of these procedures is needed. Our objective was to examine a composite outcome of major postoperative complications, including in-hospital mortality.

Materials and Methods

The Nationwide Inpatient Sample (NIS), 1998–2006, was used to identify all patients with a diagnosis of PNET who had undergone pancreatectomy. Candidate predictors consisted of patient and hospital characteristics. Univariate analyses included χ² tests. Multivariate analyses were performed with logistic regression to determine which predictors were independently associated with the composite outcome.

Results

A total of 463 (2274 nationally weighted) patients were identified. Overall composite postoperative complication rate was 29.6%. The majority of complications involved infections (11.1%), digestive complications (8.8%), or pulmonary compromise (7.3%). In-hospital mortality rate was 1.7%. High Charlson comorbidity score, procedure type of Whipple or total pancreatectomy, and urban hospital location were all associated with significantly increased complication rate. Logistic regression analysis demonstrated: Charlson score of ≥3 versus score of 0 (adjusted odds ratio (OR) 4.1, 95% confidence interval (CI) 2.1–8.3), surgery type of Whipple or total pancreatectomy versus partial pancreatectomy (adjusted OR 2.7, 95% CI 1.8–4.1), and hospital location of urban versus rural (adjusted OR 4.5, 95% CI 3.0–6.9).

Conclusions

While in-hospital mortality rates are low for surgical resection of PNETs, there is a considerable overall postoperative complication rate associated with these procedures. Careful patient and surgery selection may be the key to a surgical treatment approach for PNETs that may optimize outcomes.

Introduction

Pancreatic neuroendocrine tumors (PNETs), also referred to as islet cell tumors, are relatively rare pancreatic tumors, representing approximately 1%–2% of all pancreatic tumors [1]. Due to the rarity as well as the indolent natural history of these tumors, treatment approaches are not yet standardized, and, in particular, debate surrounds whether surgery alters the natural progression of PNETs and whether surgery should be performed in the case of metastases 2, 3, 4, 5. Previous work has shown that there is a survival advantage conferred by primary tumor resection with acceptably low rates of mortality associated with resection of PNETs [6]. What remains to be further elucidated is the overall morbidity of these procedures. Therefore, this study analyzes a composite outcome of postoperative complications, including in-hospital mortality, within this population of patients undergoing resection for PNETs. We examined the association of various patient characteristics (age, gender, race, comorbidities), procedure types, and hospital characteristics (region, location, teaching status) to identify factors that are associated with this composite outcome. We collected this information using the Nationwide Inpatient Sample (NIS), the largest national all-payer hospital in-patient care database in the U.S.

Section snippets

Patient Selection—Database

To examine national outcomes after surgical resection for pancreatic neuroendocrine tumors (PNETs), patient discharge records were identified through the Nationwide Inpatient Sample (NIS) for the years 1998–2006. Data exist for approximately 8 million hospital discharges per year from a stratified sample of 20% of nonfederal U.S. community hospitals from participating states (n = 38 in 2006), including academic and specialty hospitals [7]. The NIS is supported by the Healthcare Cost and

Patient Demographics

From 1998 through 2006, 2274 nationally weighted patient discharge records identified adult patients (≥18 y old) with a principal diagnosis of PNET and having undergone a pancreatic resection. All further data references refer to weighted numbers, the data representative of national trends. Of this cohort of patients, 1272 (55.9%) were female. The mean age for these patients was 54.6 (range 21–87) y old; 36.6% were younger than 50 y old; 46.9% were 50–69 y old; and 16.5% were 70 y or older.

Discussion

In this study, we used representative US data from the NIS to demonstrate that the overall post-operative complication rate, including in-hospital mortality for surgical resection of PNET is 29.6% from 1998 through 2006. Independently, in-hospital mortality rate over this same time period was 1.7%. Of note, all cases of in-hospital mortality were also coded to have had at least one post-operative complication. Previous work by our group has already demonstrated this low perioperative mortality

Acknowledgments

The contributions of Dr. Frederick Anderson in database provision and analytical expertise are greatly appreciated. Dr. Jennifer F. Tseng is funded by a Howard Hughes Medical Institute Early Career Award and the American Surgical Association Foundation.

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Cited by (53)

Clinical features and postoperative survival in patients with sporadic versus multiple endocrine neoplasia type 1-related pancreatic neuroendocrine tumors: An international cohort study
2022, Surgery (United States)
Citation Excerpt :
However, modern pancreatic enzyme formulations and improvements in blood glucose control via insulin infusion pumps have reduced the metabolic sequelae of total pancreatectomy, leading some to suggest that this procedure may be a potentially viable option for risk-reduction surgery with no risk of postoperative pancreatic fistula (POPF).29 Reports of surgical management of MEN1-associated PNET have demonstrated a relatively high rate of perioperative complications, mainly consisting of grade B/C POPF, suggesting that parenchymal-sparing surgery in this population is not without risk.30,31 Interestingly, this study found that MEN1 patients had a 5-fold higher rate of total pancreatectomy compared to patients with sporadic PNET, which may reflect increased enthusiasm for this approach due to the reasons mentioned above, as well as a desire to minimize the occurrence of POPF in a group that is at high risk for this complication.
The optimal surgical management of pancreatic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1 is controversial. This study sought to compare clinicopathologic characteristics and outcomes of multiple endocrine neoplasia type 1–associated and sporadic pancreatic neuroendocrine tumors from a large multi-national database.
A multi-institutional, international database of patients with surgically resected pancreatic neuroendocrine tumors was analyzed. The cohort was divided into 2 groups: those with multiple endocrine neoplasia type 1 versus those with sporadic disease. Clinicopathologic comparisons were made. Overall and disease-free survival were analyzed. Propensity score matching was used to reduce bias.
Of 651 patients included, 45 (6.9%) had multiple endocrine neoplasia type 1 and 606 sporadic pancreatic neuroendocrine tumors. Multiple endocrine neoplasia type 1–associated pancreatic neuroendocrine tumors were more common in younger patients and associated with multifocal disease at the time of surgery and higher T-stage. Lymph node involvement and the presence of metastasis were similar. Total pancreatectomy rate was 5-fold higher in the multiple endocrine neoplasia type 1 cohort. Median survival did not differ (disease-free survival 126 months multiple endocrine neoplasia type 1 vs 198 months sporadic, P > .5). After matching, survival remained similar (overall survival not reached in either cohort, disease-free survival 126 months multiple endocrine neoplasia type 1 vs 198 months sporadic, P > .5). Equivalence in overall survival and disease-free survival persisted even when patients who underwent subtotal and total pancreatectomy were excluded.
Multiple endocrine neoplasia type 1–associated pancreatic neuroendocrine tumors are more common in younger patients and are associated with multifocality and higher T-stage. Survival for patients with multiple endocrine neoplasia type 1–associated pancreatic neuroendocrine tumors is comparable to those with sporadic pancreatic neuroendocrine tumors, even in the absence of radical pancreatectomy. Consideration should be given to parenchymal-sparing surgery to preserve pancreatic function.
Small pancreatic neuroendocrine tumors: Resect or enucleate?
2021, American Journal of Surgery
The aim of this analysis is to compare the postoperative outcomes of resection and enucleation of small pancreatic neuroendocrine tumors (PNETs).
The 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.
Operative 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).
Enucleation 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.
Robustness of CT radiomic features against image discretization and interpolation in characterizing pancreatic neuroendocrine neoplasms
2020, Physica Medica
To explore the variation of the discriminative power of CT radiomic features (RF) against image discretization/interpolation in characterizing pancreatic neuro-endocrine (PanNEN) neoplasms.
Thirty-nine PanNEN patients with pre-surgical high contrast CT available were considered. Image interpolation and discretization parameters were intentionally changed, including pixel size (0.73–2.19 mm²), slice thickness (2–5 mm) and binning (32–128 grey levels) and their combination generated 27 parameter’s set. The ability of 69 RF in discriminating post-surgically assessed tumor grade (>G1), positive nodes, metastases and vascular invasion was tested: AUC changes when changing the parameters were quantified for selected RF, significantly associated to each end-point. The analysis was repeated for the corresponding images with contrast medium and in a sub-group of 29/39 patients scanned on a single scanner.
The median tumor volume was 1.57 cm³ (16%-84% percentiles: 0.62–34.58 cm³). RF variability against discretization/interpolation parameters was large: only 21/69 RF showed %COV < 20%. Despite this variability, AUC changes were limited for all end-points: with typical AUC values around 0.75–0.85, AUC ranges for the 27 parameter’s set were on average 0.062 (1SD:0.037) for all end-points with maximum %COV equal to 5.5% (mean:2.3%). Performances significantly improved when excluding the 5 mm thickness case and fixing the binning to 64 (mean AUC range: 0.036, 1SD:0.019). Using contrast images or limiting the population to single-scanner patients had limited impact on AUC variability.
The discriminative power of CT RF for panNEN is relatively invariant against image interpolation/discretization within a large range of voxel sizes and binning.
Resection Versus Observation of Small Asymptomatic Nonfunctioning Pancreatic Neuroendocrine Tumors
2020, Journal of Gastrointestinal Surgery
Management 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.
Retrospective 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.
Forty-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.
No 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.
Imaging-guided precision medicine in non-resectable gastro-entero-pancreatic neuroendocrine tumors: A step-by-step approach
2020, European Journal of Radiology
The majority of gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) are diagnosed at a non-resectable stage due to non-specific clinical syndromes, late manifestations from mass effects, or incidental detection of a clinically silent disease. Management strategies include curative or cytoreduction surgery, imaging-guided intervention, chemotherapy, immunotherapy, and radionuclide therapies. In this step-by-step review, we provide a structured approach for standardized reading and reporting of medical imaging studies covering content and terminology. This review explains which imaging studies should be used for different NETs and what should be reported when interpreting these studies. This standardized data collection guide should enable precision medicine for the management of patients with GEP-NETs of neuroectodermal origin: gastrointestinal-NETs (giNETs) and pancreatic NETs (pNETs). To improve outcomes from GEP-NETs, it contains a comprehensive evaluation of imaging aids for determining surgical non-resectability, and serves as a surrogate measure for tumor differentiation and proliferation, assessing the spatial and temporal heterogeneity of the tumor sites with prognostic and therapeutic implications.
Evaluation and Management of Neuroendocrine Tumors of the Pancreas
2019, Surgical Clinics of North America

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Oncology/EndocrineAssociation for Academic SurgeryComplications After Pancreatectomy for Neuroendocrine Tumors: A National Study

Background

Materials and Methods

Results

Conclusions

Introduction

Section snippets

Patient Selection—Database

Patient Demographics

Discussion

Acknowledgments

J Am Coll Surg

J Am Coll Surg

Surg Oncol Clin N Am

Surgery

J Clin Epidemiol

J Gastrointest Surg

Am J Surg

Cytological differentiation of asymptomatic pancreatic islet cell tumours in autopsy material

Virchows Arch A Pathol Anat Histol

Pancreatic neuroendocrine tumors: The impact of surgical resection on survival

Cancer

International Classification of Diseases, Ninth Revision, Clinical Modification

Oncology/Endocrine
Association for Academic Surgery
Complications After Pancreatectomy for Neuroendocrine Tumors: A National Study