Introduction
Pancreatic cancer is one of the most lethal
malignancies worldwide as it is diagnosed in advanced stages of the
disease, when invasion of the surrounding organs is present
(1-5).
Furthermore, despite significant progress in imaging and diagnostic
modalities, <25% of patients with pancreatic head adenocarcinoma
are diagnosed in incipient stages of the disease (1). Therefore, cases presenting limited
invasion at the level of the venous structures, such as the portal
vein, are considered to be borderline resectable lesions, while
cases presenting arterial invasion are classified as locally
advanced lesions (2,3). After the techniques of vascular
surgery improved, vascular resections have been widely implemented
and their benefits have been demonstrated, including improved
overall survival compared with cases submitted to palliative
medical treatment (3-7).
In cases where venous wall invasion occurs, it has been reported
that extended pancreatic and vascular resections are justified, and
survival rates similar to standard pancreatoduodenectomy have been
reported; however, in cases where arterial invasion is present, the
effects remain unclear (2-7).
In such cases, per primam resection vs. neoadjuvant chemotherapy
followed by resection with curative intent have been widely
analyzed so far (3-6).
Therefore, studies have focused on investigating whether arterial
resection is justified and whether they induce more harm than good
for these patients (5-7).
The present study aimed to investigate the preliminary experience
regarding arterial resection in locally advanced pancreatic head
adenocarcinoma.
Case report
After obtaining approval from the Ethics Committee
of Fundeni Clinical Institute (approval no. 151/2021), data of
patients submitted to surgery for locally advanced pancreatic
cancer at Fundeni Clinical Institute (Bucharest, Romania) between
January 2018 and January 2020 were retrospectively reviewed. After
excluding cases in which surgery with radical intent was not
feasible, due to the local extent of the disease or presence of
peritoneal or liver metastases, there were four eligible cases. All
four cases were submitted to surgery with curative intent followed
by adjuvant chemotherapy. In all cases the follow-up method
consisted of clinical examination, computed tomography and
biochemical tests every 3 months. The age range at the time of
initial diagnosis was 43-56 years (mean age, 48 years), while the
sex ratio was 3:1 (male to female). Preoperative presumptive
diagnostic was established via computed tomography and was
demonstrated via endoscopic ultrasound biopsy in all cases. The
preoperative details are presented in Table I.
 | Table IDemographic features and preoperative
evaluation of the four patients diagnosed with locally advanced
pancreatic cancer. |
Table I
Demographic features and preoperative
evaluation of the four patients diagnosed with locally advanced
pancreatic cancer.
| No. | Age, years | Sex | CA19-9, U/ml | Histopathological
type | Degree of
differentiation | Neoadjuvant
chemotherapy |
|---|
| 1 | 43 | M | 39 | PDAC | Poorly
differentiated | Yes |
| 2 | 56 | M | 412 | PDAC | Poorly
differentiated | No |
| 3 | 42 | M | 28 | PDAC | Moderately
differentiated | Yes |
| 4 | 51 | F | 386 | PDAC | Poorly
differentiated | No |
As presented in Table
II, neoadjuvant chemotherapy was administrated in two cases to
shrink the tumor volume and spare more vascular structures; in both
cases the tumor volume decreased, and the preoperative imagistic
studies revealed the absence of arterial invasion. Thus, surgery
with curative intent was attempted in both cases; however, at the
time of surgery persistent invasion at the level of the arterial
and venous structures was still present. Arterial invasion was
limited in both cases, and given that the patients did not have
other comorbidities, surgery with curative intent was performed. In
the other two cases, preoperative investigations revealed the
presence of borderline resectable lesions, the tumoral invasion
being limited to the portal vein; therefore, these two cases were
submitted to surgery with curative intent as first intention
treatment. However, limited invasion of the superior mesenteric
artery was encountered intraoperatively. In both cases, surgery
with curative intent was performed. Intraoperative details of the
surgical procedures are presented in Table II. In all but one case,
histopathological studies confirmed the presence of negative
resection margins, confirming the radicality of the surgical
procedure. Positive resection margins were encountered in a
42-year-old male who previously underwent neoadjuvant chemotherapy,
in which the inferior stump of the resected portion of the superior
mesenteric artery presented microscopic tumoral invasion.
| Table IIIntraoperative details of the patients
submitted to arterial and venous resection in association with
pancreatoduodenectomy. |
Table II
Intraoperative details of the patients
submitted to arterial and venous resection in association with
pancreatoduodenectomy.
| No. | Type of arterial
resection and reconstruction | Type of venous
resection and reconstruction | Estimated blood loss,
ml | Length of surgery,
min | Type of
resection |
|---|
| 1 | Superior mesenteric
artery resection, patch placement | Circumferential
portal vein resection, end to end anastomosis | 650 | 420 | R0 |
| 2 | Superior mesenteric
artery resection, patch placement | Circumferential
portal vein resection, end to end anastomosis | 700 | 510 | R0 |
| 3 | Superior mesenteric
artery resection, patch placement | Circumferential
portal vein resection, patch interposition | 850 | 490 | R1 |
| 4 | Superior mesenteric
artery resection, patch placement | Circumferential
portal vein resection, end to end anastomosis | 800 | 380 | R0 |
Postoperatively, a single patient developed
pancreatic leak and required emergency reoperation consisting of
totalization pancreatectomy to minimize the risk of postoperative
cataclysmic bleeding from the vascular anastomoses. The
postoperative hospital in stay ranged between 7-28 days, and there
were no postoperative mortalities. In all cases, anticoagulant
treatment was administered for the next 3 months, followed by
computed tomography to detect the patency of the vascular
reconstructions.
Postoperative follow-up consisted of clinical
examination, laboratory tests, abdominal ultrasound and computed
tomography every 3 months.
The treatment outcomes were as follows: At the 3
months follow-up, there were no vascular complications, all the
grafts and reconstructed segments being functional. Furthermore, no
signs of local or distant recurrence were observed. At the 6 months
follow-up one of the two cases presented a recurrent tumor invading
the celiac axis, while, at the 1 year follow up, another case was
diagnosed with multiple peritoneal and hepatic metastases, both
cases being further submitted to chemotherapy with palliative
intent.
Discussion
Locally advanced pancreatic cancer involving the
vascular structures has been considered for a long period of time
as unresectable and therefore patients were submitted to palliative
treatment (1-3).
However, once the surgical technique and the preoperative imagistic
techniques improved, vascular resections became more frequently
performed, the best results in terms of survival being obtained in
cases in which arterial resections were not needed, invasion being
limited to the venous structures (4-6).
Furthermore, in certain cases local invasion of the arterial
structures was observed intraoperatively and arterial resections
were therefore associated with promising results. Initially, such
cases were diagnosed with arterial invasion only intraoperatively
and radical surgery was further performed due to the low level of
invasion (5,6). Similarly, in the present study, in two
out of the four cases, arterial invasion was solely observed
intraoperatively and, due to the limited area of invasion, radical
surgery was performed, including arterial resections. In the other
two cases, arterial invasion was diagnosed initially and decreased
due to the administration of the neoadjuvant chemotherapeutic
treatment. In this respect, in these two cases, radical surgery,
including arterial resection, was performed. In all four cases, the
early postoperative course was uneventful, thus demonstrating the
feasibility and efficacy of the method.
The role of arterial resection in locally advanced
pancreatic head adenocarcinoma has been widely debated thus far,
with contradicting results (8,9). Some
studies have reported that arterial resection can significantly
improve survival, while others suggest that surgery should be
avoided when arterial resection is present (7-9).
Barreto and Kleeff (7) suggested
that this may be due to the association with perineural invasion;
therefore, as opposed to cases where venous invasion is present,
presence of the arterial wall is expected to have malignant cells
at the level of the anatomical neural plexus surrounding the
arteries, resulting in apparition of locoregional metastases
irrespective to the type of procedure performed. In addition,
presence of arterial invasion is a sign of a more aggressive
tumoral biology, which decreases the chances of achieving negative
resection margins (10). The
Japanese Society of Pancreatic Surgery reported that the presence
of arterial involvement acts as an independent prognostic factor
associated with lower rates of radical resections, negative margins
and survival rates. Furthermore, similar survival rates were
reported in cases in which negative resection margins were not
reached and cases presenting locally advanced, not surgically
treated pancreatic cancer or those with metastatic disease
(11).
With regards to cases where neoadjuvant systemic
chemotherapy has been performed, it has been suggested that initial
investigation via the ‘artery first’ approach should be applied,
followed by frozen biopsy from the surrounding tissues at the level
of the celiac axis/hepatic artery/superior mesenteric artery.
Furthermore, it has been suggested that surgery should not be
performed when remnant tumor is present (12). It has also been suggested that a
personalized approach should be taken into consideration for each
case, and arterial invasion should not be considered as a formal
contraindication for resection (13).
However, patients undergoing neoadjuvant
chemotherapy followed by surgery remains controversial. Some have
reported the superiority of this therapeutic approach compared with
chemotherapy alone. A study by Sonohara et al (14) included 44 cases diagnosed with
locally advanced pancreatic cancer, who underwent surgery with
curative intent following neoadjuvant chemotherapy. The most
performed arterial resections were hepatic artery resection in 21
cases, followed by celiac trunk resection in 12 cases, superior
mesenteric artery in six cases and splenic artery in five cases.
The authors compared the intraoperative and postoperative outcomes
of this study group to those reported in a group of 686 patients
who underwent standard pancreatoduodenectomy. Cases where arterial
resection was required were frequently associated with positive
microscopic resection margins. In addition, performing arterial
resection was significantly associated with longer intraoperative
times and increased requirement for intraoperative blood
transfusion, while the rates of intraoperative blood loss were
similar between the two groups. With regards to severe
postoperative complications, such as pancreatic leaks, the same
study group demonstrated that performing arterial resection did not
increase the risk of developing such complications. As for the
long-term outcomes, the authors demonstrated that in the last
decade, once the surgical technique improved and new
chemotherapeutic agents were identified, survival outcomes
significantly improved; therefore, the overall survival of patients
submitted to arterial resection was similar to those submitted to
standard pancreatoduodenectomy. Multivariate analysis demonstrated
that neoadjuvant and adjuvant chemotherapy were the most
significant prognostic factors that influenced long-term outcomes.
Furthermore, neoadjuvant systemic chemotherapy was associated with
increased rates of negative resection margins, which in turn
improved the long-term outcomes (14).
In conclusion, the role of arterial resection in
maximizing the radicality of surgery in locally advanced pancreatic
cancer remains controversial. Although it has been suggested that
the presence of arterial invasion should be considered as a formal
contraindication for resection, others suggest that this procedure
should be performed with neoadjuvant chemotherapy to shrink the
tumor volume.
Acknowledgements
Not applicable.
Funding
Funding: No funding was received.
Availability of data and materials
The datasets used and/or analyzed during the current
study are available from the corresponding author on reasonable
request.
Authors' contributions
NB, FF, FG, DR and MD conceived the present study.
CB, IB and IC performed the relevant literature research. FF, DR,
CSa, VB, CB, IC and FG performed formal analysis. CD, OS and CSa
performed the investigation. OS, CB and IC acquired the resources.
CSt, CB, IC and IB curated the data. IB drafted the initial
manuscript. CSa, FF, IB, IC, CB and VB drafted, reviewed and edited
the manuscript for important intellectual content. DR, CSt, CB and
IC visualized the data, while VB and IC supervised the present
study. NB, CSt, IC, CB and IB participated in the entire review
process and contributed to the analysis and critical interpretation
of the data. NB, IB, CSa, CSt, VB, IC, FF and FG confirmed the
authenticity of all the raw data. All authors have read and
approved the final manuscript.
Ethics approval and consent to
participate
The present study was approved by the Ethics
Committee of Fundeni Clinical Institute (approval no. 151/2021) and
performed in accordance with the Declaration of Helsinki. Written
informed consent was provided by all patients prior to the study
start.
Patient consent for publication
Written informed consent was provided by all
patients to publish this paper.
Competing interests
The authors declare that they have no competing
interests.
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