How to cite this article: Kelsey H, Sanji A, Jack S, Bill T, Roman B et al. Preoperative Prognostic Features of Pancreatic Head Adenocarcinoma. Open Access J Surg. 2017; 2(1): 555578. DOI: 10.19080/OAJS.2016.02.555578
Objective: The purpose of this study was to define the preoperative prognostic features in pancreatic cancer patients of Whipple procedure.
Methods: The medical records of pancreatic head adenocarcinoma patients who underwent Whipple procedure by a single surgeon from 2003 -2012 were reviewed. The cases were retrogradely analyzed in 2 groups: Group 1 (n=9) comprised of patients who lived more than 3 years, and Group 2 (n=13) comprised who died within 1 year following the surgery. Clinical data were collected by chart review, including demographic, histopatho-logic, preoperative, perioperative, and postoperative findings. Anova microsoft excel sta-tistic analysis was performed on the recorded data.
Result: Patients in Group 2, who survived less than 1 year following surgery, had statis-tically significant more poorly differentiated adenocarcinoma and less dilatation of the pancreatic duct. These patients were more often to have preoperative abdominal/back pain, weight loss and higher level of CA19-9, as compared with those of Group 1 pa-tients. Both groups showed most patients died due to metastatic disease.
Conclusion: Pancreatic adenocarcinoma is not a homogeneous disease. It is possible to find preoperative prognostic features for more appropriate management. With better pre-operative stratification, the care for these patients could be more individualized, and lead to better outcome.
Pancreatic cancer is the fourth leading cause of cancer-related mortality in the Western World, following lung, colorectal and breast cancer [1-9]. Unlike these cancers, the mortality rates for pancreatic cancer remain relatively unchanged . Without treatment, the overall 5-year survival rate is less than 10% [1,7-9,11]. Surgical resection is the only therapeutic treatment to achieve long-term survival [2,5,8,9,12]. The majority of patients have advanced disease at the time of diagnosis, thus only 10-20% of patients are considered candidates for curative resection [1,4,8,9]. Pancreaticoduodenectomy, also known as Whipple procedure, is the surgical treatment choice in patients who have resectable tumors located at the head of the pancreas, or regions adjacent to the head of the pancreas .
Although the survival rates following surgery have improved over last few decades, the prognosis following surgery remains poor, with an overall five-year survival ranging between 10 to 25% . Several studies have analyzed the determinants of short-term and long-term survival rates in post-resection pancreatic cancer patients, but the results have been inconsistent [1,2]. Finding preoperative prognostic features in clinical resectable patients will help to triage patients for appropriate treatment. The purpose of this study is to determine the preoperative prognostic factors influencing short-term and long-term survival rates in pancreatic cancer patients who were all resectable on preoperative clinical staging according to NCCN guideline.
Twenty-two of 87 Whipple procedures performed by a single
surgeon in Windsor, Ontario, Canada between March 2004 and
October 2012 were pathology confirmed pancreatic head
adenocarcinoma and survived for either less than one year or
more than 3 years after the surgery. The patients were divided
into two groups: Group 1 comprised of 9 patients who lived
more than 3 years, and Group 2 comprised of 13 patients who
died with-in 1 year, following the surgery. Potential prognostic
factors abstracted in this study included demographic,
histopathologic, preoperative, perioperative, and postoperative
factors. The primary variable analyzed in this study was survival
time after surgery. Survival time was defined from the time of
surgery to death due to pancreatic cancer-related complications.
Anova microsoft excel statistic analysis was performed on the
All 22 patients were preoperatively diagnosed and classified
as resectable pancreatic cancer according to NCCN pancreatic
cancer guideline. Indeed, all of these patients had radical
resection by means of Whipple procedure. Our results suggested
that most observation data were not statistically significant.
However, pathological differentiation and pancreatic duct
dilatation were found statistically significant different between
the two groups, while preoperative weight loss, abdominal/
back pain and CA19-9 level were trending more often in Group
2, those survived less than one year after the surgery (Tables 1
Pancreatic cancer like many other malignancies is a systemic
disease. It affects individual patient differently based on many
variables (Figure 1), including factors associated with tumor
aggressiveness, clinical background condition of the patient,
and the scope of the treatment used, amongst others [1-3]. In
order to determine the optimal treatment strategy that can be
of most beneficial for each individual patient, this study was to
investigate the variables that were responsible for the prognosis
of pancreatic cancer, particularly those in the preoperative period. For many years, Whipple procedure has been the choice
of surgical treatment for early-staged tumors . However,
systemic therapy including adjuvant chemoradiational therapy,
immunotherapy is playing roles for patient long-term survival.
Neo-adjuvant therapy before surgery has also been becoming an
important therapeutic strategy in the modern management of
pancreatic cancer patients .
This study reviewed various factors associated with survival
time in pancreatic cancer treatment. Data analysis showed no
statistically significant differences in patients’ background
health and oncological treatments including surgery and chemo/
radiation therapies between the two groups. The Whipple
procedures for all patients performed by a single surgeon kept
surgical treatment relatively identical to each patient. Therefore,
the prognosis should be reasonably believed to be depending
on the pancreatic cancer itself. A cancer causing poor prognosis
should be in one of two possible situations:
The cancer was in late stage when it was found, thus it
caused the patient’s death in short time;
The cancer was still in relatively early stage, however,
in very aggressive nature, i.e. developing very fast and killing
the patient in short time.
All our patients were clinically staged as resectable per
NCCN guideline, with similar size and lymph node involvement.
It is suggested that the difference in prognosis was most likely caused by the different natures of the cancer, instead of purely
pathological staging, between the groups. The main findings in
this study were poorly differentiated tumors and less dilatation
of the pancreatic duct predicted reduced post-operative survival
time. Pre-operative weight loss, higher level of CA 19-9, and new
abdominal/back pain were also more prevalent in short survival
group. Group 2, the patients who survived less than one year after
surgery had more poorly differentiated tumors on pathology,
denoting more aggressive tumors in these patients. This group
also had fewer patients with pancreatic duct dilatation. Possible
explanation might be that a more aggressive cancer presented
only for a shorter period of time with not enough time causing
chronic pancreatic duct obstruction and thus dilatation.
According to genomic analysis, there are 4 different
molecular subtypes in pancreatic adenocarcinoma:
Aberrantly differentiated endocrine exocrine (ADEX)
that correlate with histopathological characteristics .
Each subtype develops from different genetic mutation
pathways and carries different prognosis. Obviously,
cancers in Group 1 and Group 2 were not homogeneous in
nature/aggressiveness, even though no genetic testing was
Most of patients, who died, died of metastasis that was not
identified with preoperative imagings. This microscopic image
unidentifiable pre-operative metastasis should be considered
as phenotype of more aggressive nature of cancer, which were
more consistent in Group 2, where preoperative weight loss,
abdominal/back pain, and higher levels of CA 19-9 were more
common. Despite no statistical significance obtained these few
variables might help to identify more aggressive cancer in group
2 patients, in addition to the above mentioned preoperative
pancreatic duct non-/less dilatation.
Only 15%-20% of pancreatic cancer patients are diagnosed
with a resectable tumor, while 45%-50% are diagnosed with
metastatic disease . A tumor with no arterial tumor contact
(celiac axis CA, superior mesenteric artery SMA, common
hepatic artery) and no contact with superior mesenteric vein
(SMV) or portal vein (PV) or ≤ 180⁰ contact with no vein contour
irregularity is considered resectable . A tumor with distant
metastasis or unreconstructible SMV/PV, or pancreatic head
tumor with ≥ 180⁰ encasement of the SMA or CA, or pancreatic
body or tail tumor with ≥ 180⁰ encasement of the SMA or CA
or tumor contact with CA and aortic involvement, is considered
unresectable . Tumor staging is also important to decide
whether to treat with curative resection or neoadjuvant therapy.
Group 2 patients all died within one year after the surgery. In
other words, surgery did not benefit these patients. On the other
hand, Whipple procedure is a lengthy and extensive surgery.
Advances in medical and surgical technology have reduced
its mortality rates to less than 5%, but morbidity rates continue
to be high up to 30%-60% [5-8,10]. Postoperative complications,
include delayed gastric emptying, infections, intra-abdominal
abscess and abdominal hemorrhage, etc [1,5,9,10]. These
complications increase hospital stay, and delay postoperative
recovery and further adjuvant therapy [5,10]. Whipple procedure
also has an increased risk of perioperative and postoperative in
hospital mortality [1,5]. It is important to stratify the patients
preoperatively to prevent patients like in Group 2 from this
surgery which is futile in treatment and non-economical in
resources. Non-surgical treatment may be more appropriate for
this group of patients. Neo-adjuvant therapy could render about
one-third of borderline resectable cancer cases to resectable,
making surgical resection possible . Newly emerging Nano
Knife (Irreversible Electroporation) treatment was used to treat
non-resectable pancreatic cancer patients with good results
Appropriate triage of patients is undertaken preoperatively,
the valuable operating time and other resources could be used
more efficiently, while the patients would be treated more
effectively. Additionally, an interesting finding was that almost all
deceased patients at the time of the study had died of metastasis
(liver or lung metastasis), seldom from local recurrence. Thus,
surgery is not the only treatment for pancreatic cancer, despite
being the only treatment option leading to long-term survival.
This finding warrants effective and timely systemic therapy and
a multidisciplinary approach. The limitations of this study are
its small sample size and long sampling period. However, overall
the findings in this preliminary study were still informative and
are worth further investigation. Larger sample size with multiinstitution
involvement study in the future is warranted to
elucidate the findings and discover more clues for preoperative
Pancreatic adenocarcinoma is not a homogenous disease.
With better preoperative stratification, individualized patient
care would lead to a better outcome. Moreover, clinical
management could be more efficient, economically beneficial,
while reducing surgical wait time and sparing selected patients
from futile surgery. Patient death was found often due to
metastatic disease. Therefore, surgery seems not enough for
pancreatic cancer treatment even though it is the only one
leading to long-term survival. Early systemic cancer control (by
neo-adjuvant therapy) might be important to facilitate longterm