Content uploaded by Van den Akker
Author content
All content in this area was uploaded by Van den Akker on Jan 12, 2020
Content may be subject to copyright.
142
JOP. Journal of the Pancreas - http://pancreas.imedpub.com/ - Vol. 20 No. 5 – Nov 2019. [ISSN 1590-8577]
ORIGINAL ARTICLE
JOP. J Pancreas (Online) 2019 Nov 29; 20(5):142-150.
ABSTRACT
Background Pancreatic cancer prognosis remains poor despite recent advances. We aimed to determine prognostic factors associated with
pancreatic cancer outcome by retrospective analysis of patients who received curative surgical treatment. Methods In this retrospective
study, we analyzed 226 pancreatic cancer patients who received curative surgical treatment from January 2004 to December 2015. The
overall survival and disease-free survival rates were determined by the Kaplan- Meier method. Univariate analysis and multivariate
analysis were conducted to identify potential and independent prognostic factors. Results The estimated 1, 2, 3, and 5-year overall survival
was not associated with worse overall survival or disease-free survival. Conclusion
microvascular invasion and lymph node ratio should be thoroughly assessed as independent prognostic factors in pancreatic cancer.
Keywords Pancreatic Cancer; Prognosis; Pancreatic Fistula
Abbreviations
carcinoembryonic antigen
Correspondence
Tel +004915203877197
Fax +00493941645370
E-mail xristos_svor@yahoo.gr
Prognostic Factors in Patients with Pancreatic Adenocarcinoma and the
Impact of Pancreatic Fistula on Oncologic Outcomes
Svoronos Christos1, Tsoulfas Georgios2, Chatzis I3, Alatsakis Michael3,
Chatzitheoklitos Euthymmios4
1
2
3
4
INTRODUCTION
Pancreatic cancer constitutes a small percentage of all
cancers, but it is the fourth leading cause of cancer-related
increasing incidence and mortality rates in recent years,
pancreatic cancer is expected to be the second leading cause
of pancreatic cancers are adenocarcinomas arising from
only therapy with curative intent. The silent nature of
pancreatic cancer hinders its early-stage diagnosis despite
technological advances and modern equipment. Only 20%
radiotherapy, most patients will have recurrence, and the
cancer cells metastasize early in disease development, 85%
of patients eventually experience recurrence after curative
factors as prognostic indicators are essential to help
clinicians develop appropriate treatment strategies
tailored for each patient.
has become the “gold standard” for diagnosing and
monitoring treatment in pancreatic cancer patients over
node ratio and the total number of positive lymph nodes
scores has been recently emphasized in various cancers as
after pancreatic surgery, which can lead to serious
adverse effects on patient outcomes. The incidence rates
143
JOP. Journal of the Pancreas - http://pancreas.imedpub.com/ - Vol. 20 No. 5 – Nov 2019. [ISSN 1590-8577]
JOP. J Pancreas (Online) 2019 Nov 29; 20(5):142-150.
Statistical Analysis
Clinical characteristics were analyzed using Pearson’s
chi-square or Fisher’s exact test for categorical and
treatment to the date of occurrence of either death from
from initial surgical treatment to disease recurrence.
The Kaplan–Meier method was used to create survival
to determine potential factors, which were entered into a
independent prognostic factors.
RESULTS
Study Patients’ Characteristics
We included 226 patients with resectable pancreatic
adenocarcinoma in this retrospective study. The median age
pain in 65.93% and 47.35% patients, respectively. In the
demographic and clinic-pathological characteristics of the
study cohort is presented in (Table1).
Intra-operative Parameters
In all study cohort patients, the indication for
patients who were found to have a resectable tumor
at exploratory laparotomy underwent subsequent
underwent PPPD, classic Whipple, distal pancreatectomy,
and total pancreatectomy, respectively. Partial resection
(Table 1).
Morbidity and Mortality Rates
length of hospital stay for the entire cohort was 11.34
distal pancreatectomy range from 0% to 24% and from
and long-term survival and local recurrence.
The aim of this study was to evaluate potential
prognostic factors and to examine the relationship
local recurrence in 226 patients with resectable pancreatic
METHODS
Study Population
with resectable pancreatic adenocarcinoma underwent
preserving pancreaticoduodenectomy and Pylorus-
pancreatectomy and total pancreatectomy.
Data Collection
hospital visits, written correspondence, and telephone
interviews. The patients were followed periodically until
death, loss of contact, or the end of the study, which was
the date of surgery to the date of last follow-up or death.
Recurrence status and site, including local recurrence,
liver metastases, para-aortic lymph nodes metastases,
lung metastases, and peritoneal carcinomatosis, were
consumption, presence of diabetes mellitus, abdominal
staging based on the Union Internationale Contre le Cancer
histological type, and differentiation, resection margin
and vascular structures, postoperative complications,
mortality.
We also evaluated the number of the positive lymph
lymph nodes with the number of all lymph nodes that were
scores in pancreatic cancer prognosis, we evaluated
incorporates the C-reactive protein and albumin values,
144
JOP. Journal of the Pancreas - http://pancreas.imedpub.com/ - Vol. 20 No. 5 – Nov 2019. [ISSN 1590-8577]
JOP. J Pancreas (Online) 2019 Nov 29; 20(5):142-150.
I
II
III
IV
AJCC Stage
IB
IIB
III
IV
Distal pancreatectomy
Total pancreatectomy
Portal vein resection
Tumor Differentiation
R Status
Ro
R1
R2
N Status
Perineural Invasion
Microvascular Invasion Positive
Morbidity rate
Mortality rate
Perioperative blood transfusion
Table 1.
pancreaticoduodenectomy and distal pancreatectomy,
transfusions (Table 1).
Pathological Features
Most of the patients with resectable tumors had
pathologic evaluation of the surgical specimens revealed
adenocarcinoma was well-differentiated, moderated-
The median number of the excised lymph nodes was
(Table 1).
Survival and Prognostic Factors Analysis
6.19%, respectively (Figure 1).
We analyzed all variables to determine prognostic
factors associated with survival using the Kaplan–Meier
145
JOP. Journal of the Pancreas - http://pancreas.imedpub.com/ - Vol. 20 No. 5 – Nov 2019. [ISSN 1590-8577]
JOP. J Pancreas (Online) 2019 Nov 29; 20(5):142-150.
after pancreatectomy had local recurrence, whereas local
recurrence occurred in 65.6% of the patients without
In the univariate analyses, poorly differentiated tumor
The multivariate analysis revealed that only
independent prognost(Table 3).
(Table 2).
Multivariate Survival Analysis
in univariate survival were entered into a multivariate
analysis using the Cox proportional hazards model with
age>65 years, tumor staging, microvascular invasion,
(Table 2).
Analysis of the DFS Rates
respectively (Figure 2). The most frequent relapse type was
Figure 1.
146
JOP. Journal of the Pancreas - http://pancreas.imedpub.com/ - Vol. 20 No. 5 – Nov 2019. [ISSN 1590-8577]
JOP. J Pancreas (Online) 2019 Nov 29; 20(5):142-150.
Variables HR 95% CI p value HR 95% CI p value
0.02 17.615-31.105 0.004 0.772 0.539-1.105 0.191
0.00 20.712-50.005
<0.001
0.656 0.331- 1.302 0.386
0.01 22.563-29.085 0.719 0.460-1.124 0.275
0.018 14.552-19.320 - - 0.205
0.11 24.83-67.676 <0.001 0.451 0.42-4.817 0.036
0.02 26.281-35.247 0.635 0.63-6.422 0.176
Perineural Invasion 0.01 17.556-21.622 <0.001 0.534 0.534-1.269 0.411
Microvascular Invasion 0.05 18.862-24.480 <0.001 0.726 0.481-1.094 0.133
0.022 14.865-22.063 0.019 0.896 0.527-1.524 0.091
0.016 18.778-23.872 0.097 0.859 0.579-1.273 0.327
0.016 18.754-23.997 0.173 0.851 0.568-1.276 0.851
0.012 19.365-24.335 0.274 1.143 0.771-1.695 0.619
0.032 16.472-27.260 0.823 1.042 0.615-1.768 0.681
0.034 14.170-22.357 0.033 1.033 0.627-1.701 0.091
Blood Transfusion 0.00 18.616-29.439 0.66 1.129 0.729-1.747 0.322
Pancreatic Fistula 0.01832 19.445-26.602 0.818 1.046 0.695-1.575 0.901
0.07 22.456-31.239 0.02 1.354 0.706-2.599 0.073
R0 vs. R1 Resection 0.01 21.089-26.524 0.203 1.136 0.614-2.103 0.535
0.00 14.332-24.818
Table 2.
Figure 2.
resection.
147
JOP. Journal of the Pancreas - http://pancreas.imedpub.com/ - Vol. 20 No. 5 – Nov 2019. [ISSN 1590-8577]
JOP. J Pancreas (Online) 2019 Nov 29; 20(5):142-150.
Univariate* Multivariate†
Variables HR 95% CI p value HR P value
0.00 21.213-31.017 0.93 0.793 0.301
0.00 30.085-73.864 <0.001 - 0.291
0.00 25.677-34.787 - 0.641 0.174
0.05 16.127-20.745 - 0.700 0.157
0.00 39.846-96.905 <0.001 0.478 0.296
0.06 28.376-39.706 - 0.668 0.408
Perineural Invasion 0.06 19.881-24.346 <0.001 0.818 0.407
Vascular Invasion 0.08 18.552-24.545 0.001 0.709 0.172
0.00 18.140-24.781 0.017 0.902 0.14
0.06 20.825-27.913 0.03 0.842 0.176
0.03 21.437-27.447 0.11 0.821 0.978
0.00 21.174-26.542 0.037 1.135 0.637
0.04 18.192-29.561 0.639 1.025 0.556
0.00 16.006-25.951 0.052 1.019 0.234
Blood Transfusion 0.04 21.279-34.502 0.744 1.205 0.481
Pancreatic Fistula 0.05 23.260-32.321 0.634 1.011 0.916
vs.
0.00 25.996-40.025 0.084 - 0.349
0.07 20.006-26.605 - 1.396 -
0.00 17.950-27.976 - 1.518 -
R0 vs. R1 resection 0.00 24.973-33.811 0.097 1.178 0.36
0.00 16.057-27.699 - -
analysis.
Table 3.
DISCUSSION
Pancreatic cancer is one of the most lethal malignancies.
there are no long term survivors among patients with un-
curative resection varies form 15-25% based on the most
the actual survival rates remain disappointing, ranging
from 4.3% to 10.1%, as reported by two large population-
outcomes and prognostic factors in 226 patients with
were treated between 2004 and 2015. In the current series,
years, and the median survival was 23.129 months.
Our study revealed that age, tumor stage, and tumor
differentiation were negatively associated with prognosis,
Furthermore, perineural and microvascular invasion were
invasion in 44.25% of patients. In accordance with previous
studies, we found that although microvascular invasion is
less frequent than perineural invasion, it has a more severe
effect on survival. The reason could be that microvascular
invasion is responsible of metastatic recurrence of disease
and could lead to earlier metastasis, whereas perineural
invasion is responsible of local recurrence which is not
current rates less than 5% in certain specialized pancreatic
centers, the morbidity remains high, ranging from 25%
analysis of 221 patients with pancreatic cancer after
pancreaticoduodenectomy and found that pancreatic
underwent pancreatectomy, pancreaticoduodenectomy,
and distal pancreatectomy, respectively. We found no
provides valuable information to assist in the therapeutic
cancer, has been evaluated for pancreatic cancer as well.
148
JOP. Journal of the Pancreas - http://pancreas.imedpub.com/ - Vol. 20 No. 5 – Nov 2019. [ISSN 1590-8577]
JOP. J Pancreas (Online) 2019 Nov 29; 20(5):142-150.
unacceptably low in pancreatic cancer, recent studies
an independent prognostic factor
Improvements in pathological evaluation methods for
pancreatic cancer have increased the R1 resection rate
on survival is controversial. In the present study, R1
resection was established in 13.27% of the patients after
vs. 19.5
vs.
who underwent R0 resection compared with those
and multivariate analyses failed to show an association
provides information on the number of positive lymph
nodes as well as the total number of resected lymph nodes.
immune system, leading to a reduction in the lymphocyte
prognostic factor in several cancers, such as colorectal,
retrospective study showed that an elevated preoperative
stage pancreatic cancer. In the current study, we evaluated
shown to be a predictor of worse mid-term outcomes in
patients with borderline resectable pancreatic cancer
prognostic impact on pancreatic cancer outcomes remains
Unfortunately, the current study failed to demonstrate a
.
.
CONCLUSION
Despite recent systemic treatment advances, the
associated with statistically better survival rates after
curative resection. Currently, few predictive factors can
identify patients who will benefit the most from available
treatment options. We identified microvascular invasion,
pancreatic fistula did not have a significant impact on
survival or recurrence.
Acknowledgements
in data collection.
References
1.
2.
3.
unexpected burden of thyroid, liver, and pancreas cancers in the United
4.
5.
6.
7.
8.
up cohort. Onco Targets The
149
JOP. Journal of the Pancreas - http://pancreas.imedpub.com/ - Vol. 20 No. 5 – Nov 2019. [ISSN 1590-8577]
JOP. J Pancreas (Online) 2019 Nov 29; 20(5):142-150.
9.
10.
Preoperative neutrophil-to-lymphocyte ratio as a prognosticator in early
11.
12.
13.
Increased neutrophil-lymphocyte ratio is a poor prognostic factor in
patients with primary operable and inoperable pancreatic cancer. Br J
14.
Prognostic value of neutrophil-lymphocyte ratio and level of C-reactive
15.
16.
17.
al. Rare long-term survivors of pancreatic adenocarcinoma without
18.
survival and prognostic factors in patients with resectable pancreatic
19.
20.
21.
22.
23.
survival in locally advanced untreated pancreatic cancer. Br J Cancer
24.
independently predicts pancreatic cancer survival in patients treated
25.
26.
predicting long-term survival following pancreatic resection for ductal
27.
28.
29.
30.
31.
32.
Clinicopathologic characteristics, laboratory parameters, treatment
33.
34.
35. Buttur
36.
37.
JD, et al. The impact of lymph node number on survival in patients with
38.
RD, et al. Impact of total lymph node count and lymph node ratio on staging
39.
system in initiation and progression of pancreatic cancer. World J
40.
41.
42.
is associated with poor long-term prognosis in patients with pancreatic
43.
Preoperative independent prognostic factors in patients with borderline
resectable pancreatic ductal adenocarcinoma following curative
150
JOP. Journal of the Pancreas - http://pancreas.imedpub.com/ - Vol. 20 No. 5 – Nov 2019. [ISSN 1590-8577]
JOP. J Pancreas (Online) 2019 Nov 29; 20(5):142-150.
44.
45.
serum albumin level is a prognostic indicator for adenocarcinoma of the
46.
undergoing resection for ductal adenocarcinoma head of pancreas. Br J
47.
predicts more favourable early survival in resected pancreatic
48.
