The American Journal of Surgery xxx (xxxx) xxx

Contents lists available at ScienceDirect

The American Journal of Surgery

journal homepage: www.americanjournalofsurgery.com

Original Research Article

Survival disparities in rural versus urban patients with pancreatic

neuroendocrine tumor: A multi-institutional study from the US
neuroendocrine tumor study group
Muhammad Bilal Mirza a, 1, Jordan J. Baechle a, b, 1, Paula Marincola Smith a, Mary Dillhoff d,
George Poultsides e, Flavio G. Rocha f, Clifford S. Cho g, Emily R. Winslow h, Ryan C. Fields i,
Shishir K. Maithel c, Kamran Idrees a, *
a
Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, United States
b
School of Medicine, Meharry Medical College, Nashville, TN, United States
c
Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, United States
d
The Ohio State University Comprehensive Cancer Center, Columbus, OH, United States
e
Stanford University Medical Center, Stanford, CA, United States
f
Virginia Mason Medical Center, Seattle, WA, United States
g
Division of Hepatopancreatobiliary and Advanced Gastrointestinal Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, United States
h
University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
i
Washington University School of Medicine, St Louis, MO, United States

A B S T R A C T

Background: Pancreatic Neuroendocrine Tumors (PNETs) are indolent malignancies that often have a prolonged clinical course. This study assesses disparities in
outcomes between PNET patients who live in urban (UA) and rural areas (RA).
Methods: A retrospective cohort study was performed using the US Neuroendocrine Tumor Study Group database. PNET patients with a home zip code recorded were
included and categorized as RA or UA according to the Federal Office of Rural Health Policy. Overall survival (OS) was analyzed by Kaplan-Meier method, log-rank
test, and logistical regression.
Results: Of the 1176 PNET patients in the database, 1126 (96%) had zip code recorded. While 837 (74%) lived in UA, 289 (26%) lived in RA. RA patients had
significantly shorter median OS following primary PNET resection (122 vs 149 months, p ¼ 0.01). After controlling for income, local healthcare access, distance from
treatment center, ASA class, BMI, and T/N/M stage, living in a RA remained significantly associated with worse OS (HR 1.60, 95%CI 1.08–2.39, p ¼ 0.02).
Conclusion: Rural patients have significantly shorter OS following PNET resection compared to their urban counterparts.

1. Introduction metachronous metastases, as well as adjuvant therapies and post-

Pancreatic neuroendocrine tumors (PNETs) are rare tumors that are
generally slow-growing and have variable presentation.1 Patients with
PNETs often require multiple doctor visits over an extended period to
reach a definitive diagnosis.2,3 According to a recent survey, symptom-
atic PNET patients in the US attended an average of eight doctor visits
over 24 months after the onset of symptoms before arriving at a PNET
diagnosis.3,4 Following diagnosis and staging, operative management is
the mainstay of treatment and offers the possibility of cure, particularly
for small tumors that are diagnosed early.5 However, many patients with
PNET require multiple operations for both synchronous and
operative surveillance for many years following index resection.5,6 Often,
all or part of this care is provided at large specialized referral centers that
are frequently, if not entirely, located in large metropolitan areas.5
The multiple visits, interventions, and therapies required for the
diagnosis and management of PNETs may carry an additional burden for
patients living in rural communities who may not have straightforward
access to specialized healthcare facilities.7 Previous studies have
discovered that patients suffering from a variety of malignancies,
including brain,8 breast,9 gastric,10 colorectal,11 cervical,9 and prostate12
cancers, who live in rural communities throughout the United States
(U.S.), have shortened survival compared to their urban counterparts.

* Corresponding author. 597 Preston Research Building 2220 Pierce Ave, Nashville, TN, 37232, United States.
E-mail address: kamran.idrees@vumc.org (K. Idrees).
1
These authors contributed equally to this manuscript.

https://doi.org/10.1016/j.amjsurg.2024.03.003
Received 9 September 2023; Received in revised form 14 February 2024; Accepted 3 March 2024
0002-9610/© 2024 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.
0/).

Please cite this article as: Mirza MB et al., Survival disparities in rural versus urban patients with pancreatic neuroendocrine tumor: A multi-
institutional study from the US neuroendocrine tumor study group, The American Journal of Surgery, https://doi.org/10.1016/
j.amjsurg.2024.03.003
M.B. Mirza et al.
Fig. 1. Rural Areas determined by home zip code according to Federal Office of Rural Health Policy database.
Furthermore, newly published data have revealed that the age-adjusted
rate of cancer-related deaths is higher in rural areas than in large
metropolitan populations.13 These disparities have been attributed to
multiple factors, including socioeconomic influences, healthcare acces-
sibility, and long travel distances, all of which may contribute to delays in
diagnosis and treatment, leading to advanced disease presentation.14
Although the proportion of Americans living in rural areas has
remained constant at approximately 19% since 2010,15 rural hospitals
and medical centers have been closing at an alarming rate, reaching an
all-time high in 2019.16 This recent decline in the number of rural hos-
pitals and treatment facilities further limits the accessibility of medical
care for patients in rural communities, leading to a reciprocal rise in
urban-rural disparities in cancer-related outcomes.
The influence of rural living on the survival outcomes of patients
undergoing treatment for PNETs in the US remains unexamined. The
primary purpose of this study was to determine whether there are dis-
parities in survival outcomes between patients living in urban versus
rural US zip codes who underwent surgical excision of PNETs.
2. Methods
The U.S. The Neuroendocrine Tumor Study Group (US-NETSG) is a
collaboration of eight academic medical centers: Vanderbilt University
Medical Center (VUMC), Emory University, Stanford University, John
Hopkins University, Ohio State University, and Washington University in
St. Louis University of Michigan, University of Wisconsin. Adult patients
who underwent resection of gastroenteropancreatic neuroendocrine tu-
mors (stages I-IV) between 2000 and 2016 were retrospectively identi-
fied and analyzed at each institution. Data collection was approved by
the institutional review board (IRB) of each participating institution
(VUMC IRB protocol #170730).
More than 750 parameters were collected from the database for each
patient, including but not limited to demographics, general health in-
formation and comorbidities, preoperative imaging and laboratory data,
intraoperative data, pathology data, postoperative complications, time to
progression, recurrence, and death. The seventh edition of the American
Joint Commission on Cancer Staging Manual seventh edition17 was used
to define TNM classification. Tumor grade was determined based on
available data in the final pathology report and defined by the 2017
World Health Organization diagnostic criteria.18 Survival data, including
the date of the last follow-up and the date of death, were determined by
chart review. De-identified data from each institution were shared among
2
The American Journal of Surgery xxx (xxxx) xxx
the collaborating institutions for analysis.
Patients without U.S. home zip code information recorded in the
USNET-SG database were excluded from the study. Zip codes were
designated as either rural or urban according to the Federal Office of
Rural Health Policy database,19 and patients were grouped accordingly.
Patients’ home zip codes were additionally used to estimate income level
(high or low income) and examine the levels of healthcare professionals
per capita (living in an area with a healthcare worker shortage or not), as
designated by the Federal Center for Medicare and Medicaid Services
Database.20 The primary treatment center was defined as the medical
center where the index PNET resection was performed. The primary
outcome was overall survival (OS), defined as the time from the index
operation to death. Progression-free survival (PFS), recurrence-free sur-
vival (RFS), and disease-specific survival (DSS) were analyzed as sec-
ondary outcomes and calculated from the time of the index operation to
disease progression, recurrence, and disease-specific death, respectively.
Demographic and clinical factors were compared between the groups.
Categorical variables were compared using the chi-squared test or
Fisher's exact test, whereas continuous variables were compared using
the Kruskal–Wallis test. OS was calculated using the Kaplan–Meier
method and compared using the log-rank test. Clinical and pathological
data were analyzed using univariate and multivariate Cox regression
analyses. The proportional hazards assumption was tested using
Schoenfeld residuals, which did not show any significant deviation from
the proportional hazards' assumption (p ¼ 0.12). The significance
threshold was set at p < 0.05. All statistical analyses were performed
using 1.1.383 R statistics software (R Core Team, Vienna, Austria).
3. Results
Of the 1176 patients with PNET in the US-NETSG database, 1126
(96%) had available zip code data and were included in our analysis.
Overall, 579 (51.4%) were male, the median age was 57.5 (range, 22–82)
years, and the median follow-up time was 35.1 months (range:0–226
months).
Among our study cohort, 837 (74%) had urban zip codes and 289
(26%) had rural zip codes (Fig. 1). The two groups were similar in sex (p
¼ 0.284), ASA class (p ¼ 0.053), rates of preoperative comorbidities
(including hypertension (HTN), diabetes mellitus (DM) (p ¼ 0.399),
chronic obstructive pulmonary disease (COPD) (p ¼ 0.078), congestive
heart failure (CHF) (p ¼ 0.291)), and smoking (p ¼ 0.345), as well as
tumor size (p ¼ 0.454), T (p ¼ 0.120) N (p ¼ 0.871) and M (p ¼ 0.778)
M.B. Mirza et al. The American Journal of Surgery xxx (xxxx) xxx

Table 1
Demographics and tumor pathology in urban versus rural PNET patients.
Variable Urban Rural p-value

N (%) N (%)

Total 837 (74%) 289 (26%)

Distance from Treatment Center, miles – Median [IQR] 39.1 [17.3; 108.0] 88.5 [52.7; 155.0] <0.001
Lives in Health Professional Shortage Areaa Yes 320 (38.2) 163 (56.4) <0.001
No 517 (61.8) 126 (43.6)
Lives in Low Income Areab Yes 349 (41.7) 181 (62.6) <0.001
No 488 (58.3) 108 (37.4)
Insurance Status Insured 791 (94.5) 273 (94.5) 0.424
Uninsured 20 (2.4) 4 (1.4)
Unknown 26 (3.1) 12 (4.2)
Gender Male 428 (51.1) 159 (55.0) 0.284
Female 409 (48.9) 130 (45.0)
Race White 623 (74.4) 239 (82.7) 0.007
Black 79 (9.4) 13 (4.5)
Other 135 (16.1) 37 (12.8)
Age – Median [IQR] 56.9 [46.9; 65.0] 58.3 [49.0; 67.1] 0.049
ASA Class I 19 (2.3) 10 (3.5) 0.053
II 331 (39.5) 95 (32.9)
III 451 (53.9) 164 (56.8)
Unknown 36 (4.3) 20 (6.9)
ECOG Performance Status 0 562 (67.1) 153 (52.9) <0.001
1 90 (10.8) 25 (8.65)
2 9 (1.1) 2 (0.7)
Unknown 176 (21.0) 109 (37.7)
BMI – Median [IQR] 27.5 [24.0; 32.0] 28.2 [24.7; 33.6] 0.042
Functional Status Independent 709 (84.7) 210 (72.7) <0.001
Dependentc 35 (4.2) 7 (2.4)
Unknown 93 (11.1) 72 (24.9)
Hypertension Yes 345 (41.2) 134 (46.4) 0.129
No 473 (56.5) 145 (50.2)
Unknown 19 (2.3) 10 (3.5)
Diabetes Mellitus Yes - IDDM 62 (7.4) 23 (8.0) 0.399
Yes - NIDDM 111 (13.2) 45 (15.6)
No 645 (77.1) 211 (73.0)
Unknown 19 (2.3) 10 (3.5)
COPDd Yes 8 (1.0) 7 (2.4) 0.078
No 811 (96.9) 272 (94.1)
Unknown 18 (2.2) 10 (3.5)
CHFe Yes 9 (1.1) 1 (0.4) 0.291
No 810 (96.8) 278 (96.2)
Unknown 18 (2.2) 1 (0.4)
Smoking History Yes 115 (14.1) 46 (16.7) 0.345
No 698 (85.9) 229 (83.3)
Symptomatic Yes 511 (61.1) 134 (46.4) <0.001
No 326 (38.9) 155 (53.6)
Tumor Location Head 254 (30.3) 84 (29.1) 0.831
Uncinate/Neck 76 (9.1) 22 (7.6)
Body 161 (19.2) 54 (18.7)
Tail 342 (40.9) 127 (43.9)
Unknown 4 (0.5) 2 (0.7)
Operative Intent Curative 769 (91.9) 266 (92.0) 1.000
Noncurative 68 (8.1) 23 (8.0)
Tumor Sizef, cm – Median [IQR] 2.2 [1.4; 4.0] 2.5 [1.5; 3.8] 0.454
T Stage T1 353 (42.2) 100 (34.6) 0.120
T2 251 (30.0) 102 (35.3)
T3 218 (26.0) 83 (28.7)
Tx 15 (1.8) 4 (1.4)
N Stage N0 482 (57.6) 163 (56.4) 0.871
N1 227 (27.1) 83 (28.7)
Nx 128 (15.3) 43 (14.9)
M Stage M0 718 (85.8) 243 (84.1) 0.778
M1 104 (12.4) 40 (13.8)
Mx 15 (1.8) 6 (2.1)
Tumor Gradeg G1 525 (62.7) 167 (57.8) 0.225
G2 224 (26.8) 83 (28.7)
G3h 31 (3.7) 18 (6.2)
Unknown 57 (6.8) 21 (7.3)

Table 1. IQR ¼ Interquartile Range; aHealth Professional Shortage Area (HPSA) and bLow Income Area (LIA) determined by home zip code according to Federal Center
for Medicare and Medicaid Services Database; ASA American Society of Anesthesiologists (ASA) Physical Status classification system; Eastern Cooperative Oncology
Group (ECOG); Body Mass Index (BMI); cDependent ¼ partial and complete dependence; dCOPD ¼ Chronic obstructive pulmonary disease; eCHF ¼ Congestive heart
failure; fTumor Size ¼ tumor size on final pathology following resection; IDDM ¼ Insulin Dependence Diabetes Mellitus; NIDDM ¼ Non-Insulin Dependence Diabetes
Mellitus; g2017 World Health Organization diagnostic criteria; hG3 ¼ Neuroendocrine Carcinoma G3 þ Neuroendocrine Tumor G3.

3
M.B. Mirza et al. The American Journal of Surgery xxx (xxxx) xxx

stage, and tumor grade on final pathology report at index resection (p ¼
0.225). Compared to the urban group, patients in the study cohort who
lived in rural communities were slightly older (median age 58 vs. 57
years, p ¼ 0.049), had a slightly higher median body mass index (BMI,
28.2 vs 27.5, p ¼ 0.043), were more likely to be white (83 vs. 74%, p ¼
0.007), had higher rates of unknown ECOG performance status (p <
0.001), and were less likely to be symptomatic on presentation (46 vs.
61%, p < 0.001, Supplemental Table 1). Patient demographics and tumor
pathology are summarized in Table 1. Within the study cohort, patients
living in rural areas were also more likely to live in low-income areas (63
vs. 42%, p < 0.001) and in areas with a shortage of healthcare pro-
fessionals (56 vs. 38%, p < 0.001).Patients from rural and urban areas
had similar lengths of stay and postoperative complication rates, which
are summarized in Supplemental Table 2. Rural patients lived further
from their primary treatment center (median 89 vs. 39 miles, p < 0.001,
Supplemental Fig. 1). The distribution of rural and urban patients
contributing to the cohort was relatively consistent throughout the
duration of the study, with a median rural portion of 26.0% per year
(range 19.5–39.1%, Supplemental Fig. 2).
Patients living in rural areas had a significantly shorter OS (122 vs.
149 months, p ¼ 0.011) than those living in urban areas (Fig. 2). One-, 5-,
and 10-year survival rates for urban patients were 97.5%, 88.6%, and
69.0%, respectively, compared to 93.6%, 79.0%, and 62.9%, respec-
tively, for rural patients. There was no significant difference in PFS (5-
year PFS 64 vs. 62%, p ¼ 0.539), RFS (5-year RFS 78 vs. 75%, p ¼ 0.460),
or DSS (5-year DSS 90 vs. 93%, p ¼ 0.756) between the rural and urban
groups (Supplemental Figs. 3a–c). The median PFS was 104 months in
patients with PNETs from urban areas. The median PFS was not met for
PNET patients from rural areas. The median OS, RFS, and DSS were not
met for either the rural or urban groups.
On multivariable analysis controlling for BMI, age, ASA class, TNM
stage, distance to primary treatment center, living in an area with
shortages of healthcare professionals, and living in a low-income area,
living in a rural area was independently associated with worse OS from
the date of PNET diagnosis (hazard ratio [HR] 1.60, 95% confidence
interval [CI] 1.08–2.39, p ¼ 0.021) (Fig. 3).
4. Discussion
In the United States, 60 million individuals residing in rural areas are
disproportionately affected by chronic and malignant diseases, with
notable disparities in survival rates across various cancer types and
chronic conditions when compared to those living in urban
settings.8–12,21–23 Although neoplastic, the indolent nature of PNETs
often requires protracted maintenance therapies and re-operations over
many years, resulting in a clinical course similar to that of chronic con-
ditions. This extended treatment trajectory often demands recurrent
visits to healthcare providers and treatment centers over several years,
imposing a significant burden on those without convenient access to
specialized healthcare services, particularly patients in rural commu-
nities. Concurrently, the opportunity for early and regular interventions
in PNETs presents a substantial potential to markedly influence disease
progression and survival outcomes, underscoring the importance of
timely and accessible treatment in impacting patient prognoses.5,6
Our study demonstrates that patients undergoing surgery for PNETs
living in rural areas have significantly worse OS compared to their
counterparts living in urban areas. We identified several contributing
factors to this disparity, including lower income and restricted access to
healthcare professionals locally, both of which have been linked to
adverse health and cancer-outcomes.24–26 Second, the chronicity of PNET

Table 2
Patient management factors in urban versus rural PNET patients.
Variable Urban Rural p-value

N (%) N (%)

Total 837 (74%) 289 (26%)

Time to OR from Date of Diagnosism, days – Median [IQR] 52.0 [24.0; 124] 55.5 [28.0; 121] 0.400
Duration of Follow-upn, months -Median [IQR] 34.9 [12.0; 67.0] 31.9 [8.57; 59.6] 0.062
Preoperative CT imaging Yes 788 (94.1) 273 (94.5) 0.957
No 49 (5.9) 16 (5.5)
Preoperative MRI imaging Yes 288 (34.4) 91 (31.5) 0.404
No 549 (65.6) 198 (68.5)
Multiple (≥2) Preoperative Imaging Studies Yes 391 (47.7) 111 (39.2) 0.016
No 428 (52.3) 172 (60.8)
Emergency Surgery Yes 11 (1.3) 2 (0.7) 0.533
No 826 (98.7) 287 (99.3)
Postoperative Imaging Frequency None 123 (14.7) 40 (13.8) 0.293
q3-4 months 159 (19.0) 39 (13.5)
q6 months 171 (20.4) 70 (24.2)
Annual 197 (23.5) 70 (24.2)
Unknown 187 (22.3) 70 (24.2)
Pre-operative XRT Yes 3 (0.4) 1 (0.4) 1.000
No 834 (99.6) 288 (99.7)
Post-operative XRT Yes 12 (1.4) 2 (0.7) 0.538
No 825 (98.6) 287 (99.3)
Neoadjuvant Chemotherapy Yes 32 (3.8) 14 (4.8) 0.559
No 805 (96.2) 275 (95.2)
Neoadjuvant Somatostatin Analog Yes 16 (1.9) 8 (2.8) 0.527
No 821 (98.1) 281 (97.2)
Adjuvant Chemotherapy Yes 31 (3.7) 14 (4.8) 0.497
No 806 (96.3) 275 (95.2)
Adjuvant Yes 8 (0.9) 1 (0.4) 0.461
MTOR Inhibitor No 829 (99.0) 288 (99.7)
Adjuvant Yes 71 (8.5) 23 (8.0) 0.877
Somatostatin Analog No 766 (91.5) 266 (92.0)
Reported Cause of Death Yes 661 (79.0) 236 (81.7) 0.371
No 176 (21.0) 53 (18.3)

Table 2. OR ¼ Operating Room on date of index operation; mTime to OR from diagnosis measured from earliest date of first imaging or first oncology visit; nDuration of
Follow-up measure from date of discharge of index operation till last follow-up; IQR ¼ Interquartile Range; XRT ¼ radiation therapy; MTOR ¼ mammalian target of
rapamycin.

4
M.B. Mirza et al.
Fig. 2. Overall survival in urban versus rural PNET patients from date of index operation.
management has been shown to be financially burdensome, as it involves
direct medical costs associated with diagnoses and treatment, frequent
follow-up visits, and symptom burden that can impact employability and
thus overall patient well-being.27–31 Notably, PNET patients face a higher
financial burden compared to those with more common gastrointestinal
cancers like colon cancer, with the highest costs accruing several months
to several years after diagnosis.7
In our study, rural patients were observed to be slightly older and had
a marginally higher BMI compared to their urban counterparts. Never-
theless, when these factors were adjusted for in a multivariable analysis,
residing in a rural zip code still emerged as an independent predictor of
reduced overall survival. Our findings indicate that patients with PNETs,
regardless of living in rural or urban areas, received similar levels of care
5
The American Journal of Surgery xxx (xxxx) xxx
Fig. 3. Rural Areas determined by home zip code
according to Federal Office of Rural Health Policy
database; Travel Distance calculated by geographical
distance from home zip code to primary treatment
center zip code; Health Professional Shortage Area
(HPSA) and Low Income Area (LIA) determined by
home zip code according to Federal Center for Medi-
care and Medicaid Services Database; BMI ¼ Body
Mass Index; Age at time of resection; ASA American
Society of Anesthesiologists (ASA) Physical Status
classification system.
both before and after surgery. However, the logistical hurdles associated
with obtaining comprehensive cancer care might have led to delays or
inadequate care for rural patients. Regrettably, the absence of data from
the US Neuroendocrine Tumor Study Group (US-NETSG) limits further
exploration into possible delays in diagnosis and treatment that may
account for the survival differences observed.
While there was a significant difference in OS between urban and
rural patients at 1-, 5-, and 10-years post-index resection, we did not see a
significant difference in PFS, DFS, or DSS between the treatment groups.
This suggests that factors other than PNET progression, such as comor-
bidities or access to care, might influence the observed disparity.
Although patients with PNET typically have favorable disease-specific
mortality, many surgical and medical interventions associated with PNET
M.B. Mirza et al.
treatment are associated with significant morbidity.32,33 Although post-
operative complications and readmission rates were similar between
patients from rural and urban areas, it is possible that patients living in
rural areas may lack access to the supportive care necessary to manage
these complications.
Our study, although comprehensive, has some limitations. First, its
retrospective nature constrains our capacity to deduce causality and as
with many large national databases, the US-NETSG database contains
missing data.34 While we observed a shorter overall survival for rural
patients post-PNET resection, the US-NETSG database did not encompass
certain critical variables including health literacy levels, the interval
between symptom onset and PNET diagnosis, and adherence to adjuvant
treatment regimens. Next,. The patient zip code was used to approximate
the socioeconomic status and access to local medical care. Although these
are helpful approximations, the zip code data may not be entirely
representative of the sample population. While US-NETSG institutions
primarily serve urban areas, our study's inclusion of rural patients is
significant. However, this urban focus may introduce bias, raising ques-
tions about the broader applicability of our findings. Although most
patients underwent index resection at high-volume US-NETSG centers,
nonoperative treatment locations remained uncertain. Despite similar
follow-up durations between rural and urban groups, rural patients may
have sought care from unlisted US-NETSG facilities. Despite the extensive
10-year follow-up period, our study failed to achieve the median overall
survival. To assess the disparities in survival rates between rural and
urban patients throughout the entire duration, we employed the log-rank
test. In our methodology, we employed straight-line distances to gauge
the proximity between patients' residences and treatment centers. This
approach, albeit practical, might not mirror actual travel constraints.
(Supplemental Fig. 1).
Our study indicates that limited access to specialized healthcare in
rural communities may contribute to disparities in survival outcomes. As
such, improving access to specialized care has the potential to improve
the prognosis of patients residing in rural areas. Less than 3% of oncol-
ogists and endocrinologists work in rural areas,35–38 which significantly
limits access to specialized oncological care for PNETs in rural commu-
nities. Multiple strategies, including telehealth communication between
local practitioners and specialists, as well as collaborative partnerships
and outreach programs between rural and urban healthcare facilities,
have been found to be effective in reducing disease burden across mul-
tiple malignancies and in managing chronic diseases.39,40 These initia-
tives facilitate remote consultations, share medical resources,
knowledge, and expertise, and improve access to specialized medical
services.41 Establishing similar partnerships in perioperative manage-
ment for PNET patients in rural areas can be beneficial and instrumental
in reducing disparities in outcomes. Additionally, policy changes, such as
increased funding for rural healthcare facilities and expanding Medicaid
in rural areas, as well as transportation assistance programs, can help
overcome barriers to specialized healthcare delivery in rural
communities.
In conclusion, our study suggests that patients with PNET from rural
areas have shortened survival times compared to patients who live in
urban communities. While the reasons for this disparity in survival are
not entirely clear, it is likely that the observed findings are due to im-
pediments in accessing preoperative and/or postoperative care. Hence,
patients residing in rural areas may benefit from strategies that focus on
providing improved access to perioperative medical care.
CRediT authorship contribution statement
Muhammad Bilal Mirza: Conceptualization, Methodology, Writing –
original draft, Writing – review & editing. Jordan J. Baechle: Concep-
tualization, Formal analysis, Writing – original draft, Data curation.
Paula Marincola Smith: Conceptualization, Data curation, Formal
analysis, Methodology, Writing – original draft. Mary Dillhoff: Data
curation, Investigation, Writing – review & editing, Conceptualization,
6
The American Journal of Surgery xxx (xxxx) xxx
Formal analysis, Writing – original draft, Data curation, Data curation,
Writing – review & editing, Data curation, Investigation, Writing – re-
view & editing, Data curation, Investigation, Writing – review & editing,
Data curation, Investigation, Writing – review & editing, Data curation,
Investigation, Writing – review & editing, Conceptualization, Data
curation, Formal analysis, Methodology, Writing – original draft, Data
curation, Investigation, Writing – review & editing, Data curation,
Investigation, Writing – original draft. George Poultsides: Data curation,
Investigation, Writing – original draft. Flavio G. Rocha: Data curation,
Investigation, Writing – review & editing. Clifford S. Cho: Data curation,
Investigation, Writing – review & editing. Emily R. Winslow: Data
curation, Writing – review & editing. Ryan C. Fields: Data curation,
Investigation, Writing – review & editing. Shishir K. Maithel: Data
curation, Investigation, Writing – review & editing. Kamran Idrees:
Conceptualization, Data curation, Formal analysis, Investigation, Meth-
odology, Supervision, Writing – original draft, Writing – review &
editing.
Declaration of competing interest
The authors declare that they have no conflicts of interest.
Appendix A. Supplementary data
Supplementary data to this article can be found online at https://doi.
org/10.1016/j.amjsurg.2024.03.003.
References
1. Halfdanarson TR, Rubin J, Farnell MB, Grant CS, Petersen GM. Pancreatic endocrine
neoplasms: epidemiology and prognosis of pancreatic endocrine tumors. Endocr Relat
Cancer. 2008;15(2):409–427. https://doi.org/10.1677/ERC-07-0221.
2. Milan SA, Yeo CJ. Neuroendocrine tumors of the pancreas. Curr Opin Oncol. 2012;
24(1):46–55. https://doi.org/10.1097/CCO.0b013e32834c554d.
3. Basuroy Ron, Bouvier C, Ramage JK, et al. Delays and routes to diagnosis of
neuroendocrine tumors. BMC Cancer. 2018;18:1122. https://doi.org/10.1186/
s12885-018-5057-3.
4. Basuroy R, Bouvier C, Ramage JK, Sissons M, Kent A, Srirajaskanthan R. Presenting
symptoms and delay in diagnosis of gastrointestinal and pancreatic neuroendocrine
tumours. Neuroendocrinology. 2018;107(1):42–49. https://doi.org/10.1159/
000488510.
5. Schurr PG, Strate T, Rese K, et al. Aggressive surgery improves long-term survival in
neuroendocrine pancreatic tumors. Ann Surg. 2007;245(2):273–281. https://doi.org/
10.1097/01.sla.0000232556.24258.68.
6. Birnbaum DJ, Turrini O, Vigano L, et al. Surgical management of advanced
pancreatic neuroendocrine tumors: short-term and long-term results from an
international multi-institutional study. Ann Surg Oncol. 2015;22(3):1000–1007.
https://doi.org/10.1245/s10434-014-4016-8.
7. Hallet J, Law CHL, Cheung M, et al. Patterns and drivers of costs for neuroendocrine
tumor care: a comparative population-based analysis. Ann Surg Oncol. 2017;24(11):
3312–3323.
8. Urhie O, Turner R, Lucke-Wold B, et al. Glioblastoma survival outcomes at a tertiary
hospital in appalachia: factors impacting the survival of patients following
implementation of the stupp protocol. World Neurosurg. 2018;115:e59–e66. https://
doi.org/10.1016/j.wneu.2018.03.163.
9. Moss JL, Liu B, Feuer EJ. Urban/rural differences in breast and cervical cancer
incidence: the mediating roles of socioeconomic status and provider density. Wom
Health Issues. 2017;27(6):683–691. https://doi.org/10.1016/j.whi.2017.09.008.
10. Rana N, Gosain R, Lemini R, et al. Socio-demographic disparities in gastric
adenocarcinoma: a population-based study. Cancers. 2020;12(1):157. https://
doi.org/10.3390/cancers12010157. Published 2020 Jan 9.
11. Raman V, Adam MA, Turner MC, et al. Disparity of colon cancer outcomes in rural
America: making the case to travel the extra mile. J Gastrointest Surg. 2019;23:
2285–2293. https://doi.org/10.1007/s11605-019-04270-5.
12. Maganty A, Sabik LM, Sun Z, et al. Under treatment of prostate cancer in rural
locations. J Urol. 2020;203(1):108–114. https://doi.org/10.1097/
JU.0000000000000500.
13. Henley SJ, Anderson RN, Thomas CC, Massetti GM, Peaker B, Richardson LC.
Invasive cancer incidence, 2004-2013, and deaths, 2006-2015, in nonmetropolitan
and metropolitan counties—United States. MMWR Surveill Summ. 2017;66(14):1–13.
https://doi.org/10.15585/mmwr.ss6614a1PubMedGoogleScholarCrossref.
14. Unger JM, Moseley A, Symington B, Chavez-MacGregor M, Ramsey SD,
Hershman DL. Geographic distribution and survival outcomes for rural patients with
cancer treated in clinical trials. JAMA Netw Open. 2018;1(4):e181235-e181235.
15. US Census Bureau. Measuring America: Our Changing Landscape; 2016. https
://www.census.gov/content/dam/Census/library/visualizations/2016/comm/acs-
rural-urban.pdf. Accessed May 17, 2018. Published December 8.
M.B. Mirza et al.
16. TheChartisCenterforRuralHealth.StabilityofRuralHealthSafety. Net. Chartis Center for
Rural Healthcare 2019. Chicago, IL: Chartis Group LLC; 2019. https://www.ivant
ageindex.com/wp-content/uploads/2019/02/Chartis-Center-for-Rural-Health_Rur
al-Health-Safety-Net_Infographic-01.21.19_FNL.pdf.
17. Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of
the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17(6):
1471–1474.
18. Kl€
oppel G, Klimstra DS, Hruban RH, et al. Pancreatic neuroendocrine tumors: update
on the new World Health Organization classification. AJSP: Reviews & Reports. 2017;
22(5):233–239.
19. Federal Office of Rural Health Policy Database. 2018.
20. Strumolo A. Database of HPSA and Low-Income ZIP Codes for Issuers Subject to the
Alternate ECP Standard for the Purposes of QHP Certification; March 2013:1–10. htt
ps://data.cms.gov/.
21. Trivedi T, Liu J, Probst J, Merchant A, Jhones S, Martin AB. Obesity and obesity-
related behaviors among rural and urban adults in the USA. Rural Rem Health. 2015;
15(4):3267.
22. Falasinnu T, Chaichian Y, Palaniappan L, Simard JF. Unraveling race, socioeconomic
factors, and geographical context in the heterogeneity of lupus mortality in the
United States. ACR Open Rheumatol. 2019;1(3):164–172. https://doi.org/10.1002/
acr2.1024. Published 2019 Apr 29.
23. Croft JB, Wheaton AG, Liu Y, et al. Urban-rural county and state differences in
chronic obstructive pulmonary disease - United States, 2015. MMWR Morb Mortal
Wkly Rep. 2018;67(7):205–211. https://doi.org/10.15585/mmwr.mm6707a1.
Published 2018 Feb 23.
24. O'Connor JM, Sedghi T, Dhodapkar M, Kane MJ, Gross CP. Factors associated with
cancer disparities among low-, medium-, and high-income US counties. JAMA Netw
Open. 2018;1(6):e183146. https://doi.org/10.1001/jamanetworkopen.2018.3146.
Published 2018 Oct 5.
25. Tan X, Camacho F, Marshall VD, Donohoe J, Anderson RT, Balkrishnan R.
Geographic disparities in adherence to adjuvant endocrine therapy in Appalachian
women with breast cancer. Res Soc Adm Pharm. 2017;13(4):796–810. https://
doi.org/10.1016/j.sapharm.2016.08.004.
26. Adams SA, Choi SK, Khang L, et al. Decreased cancer mortality-to-incidence ratios
with increased accessibility of federally qualified health centers. J Community Health.
2015;40(4):633–641. https://doi.org/10.1007/s10900-014-9978-8.
27. Chauhan A, Agrawal R, Edwins R, et al. Out-of-pocket Spending (OOPS) and Financial
Toxicity Survey for Neuroendocrine Tumor (NET) Patients. 2020.
28. Broder MS, Chang E, Reddy SR, Neary MP. Treatment patterns and burden of illness
in patients initiating targeted therapy or chemotherapy for pancreatic
neuroendocrine tumors. Pancreas. 2017;46(7):891–897. https://doi.org/10.1097/
MPA.0000000000000872.
29. Leyden J, Pavlakis N, Chan D, et al. Patient-reported experience of the impact and
burden of neuroendocrine tumors: oceania patient results from a large global survey.
Asia Pac J Clin Oncol. 2018;14(3):256–263. https://doi.org/10.1111/ajco.12785.
The American Journal of Surgery xxx (xxxx) xxx
30. Hallet J, Davis LE, Mahar AL, et al. Patterns of symptoms burden in neuroendocrine
tumors: a population-based analysis of prospective patient-reported outcomes. Oncol.
2019;24(10):1384–1394. https://doi.org/10.1634/theoncologist.2019-0112.
31. Singh S, Granberg D, Wolin E, et al. Patient-Reported burden of a neuroendocrine
tumor (NET) diagnosis: results from the first global survey of patients with NETs.
J Glob Oncol. 2016;3(1):43–53. https://doi.org/10.1200/JGO.2015.002980.
Published 2016 Jun 8.
32. Partelli S, Tamburrino D, Cherif R, et al. Risk and predictors of postoperative
morbidity and mortality after pancreaticoduodenectomy for pancreatic
neuroendocrine neoplasms: a comparative study with pancreatic ductal
adenocarcinoma. Pancreas. 2019;48(4):504–509. https://doi.org/10.1097/
MPA.0000000000001273.
33. Atema JJ, Jilesen AP, Busch OR, van Gulik TM, Gouma DJ, Nieveen van Dijkum EJ.
Pancreatic fistulae after pancreatic resections for neuroendocrine tumours compared
with resections for other lesions. HPB (Oxford). 2015;17(1):38–45. https://doi.org/
10.1111/hpb.12319.
34. Hoskin TL, Boughey JC, Day CN, Habermann EB. Lessons learned regarding missing
clinical stage in the National Cancer Database. Ann Surg Oncol. 2019. https://
doi.org/10.1245/s10434-018-07128-3.
35. Kirkwood MK, Bruinooge SS, Goldstein MA, Bajorin DF, Kosty MP. Enhancing the
American Society of Clinical Oncology workforce information system with
geographic distribution of oncologists and comparison of data sources for the
number of practicing oncologists. J Oncol Pract. 2014;10(1):32–38. https://doi.org/
10.1200/JOP.2013.001311.
36. Lu H, Holt JB, Cheng YJ, Zhang X, Onufrak S, Croft JB. Population-based geographic
access to endocrinologists in the United States, 2012. BMC Health Serv Res. 2015;15:
541. https://doi.org/10.1186/s12913-015-1185-5. Published 2015 Dec 7.
37. Campbell NC, Ritchie LD, Cassidy J, Little J. Systematic review of cancer treatment
programmes in remote and rural areas. Br J Cancer. 1999;80(8):1275–1280. https://
doi.org/10.1038/sj.bjc.6690498PubMedGoogleScholarCrossref.
38. Sabesan S, Larkins S, Evans R, et al. Telemedicine for rural cancer care in North
Queensland: bringing cancer care home. Aust J Rural Health. 2012;20(5):259–264.
https://doi.org/10.1111/j.1440-1584.2012.01299.x.
39. Mainous 3rd AG, King DE, Garr DR, Pearson WS. Race, rural residence, and control of
diabetes and hypertension. Ann Fam Med. 2004;2(6):563–568. https://doi.org/
10.1370/afm.119.
40. Tamagno G, Sheahan K, Skehan SJ, et al. Initial impact of a systematic
multidisciplinary approach on the management of patients with
gastroenteropancreatic neuroendocrine tumor. Endocrine. 2013;44(2):504–509.
https://doi.org/10.1007/s12020-013-9910-5.
41. Pare G, Moqadem K, Pineau G, St-Hilaire C. Clinical effects of home telemonitoring
in the context of diabetes, asthma, heart failure and hypertension: a systematic
review. J Med Internet Res. 2010;12(2):e21. https://doi.org/10.2196/jmir.1357.
Published 2010 Jun 16.