ORIGINAL
ARTICLE
JOP. J Pancreas (Online)
2010 Sep 6; 11(5):434-438.
Synchronous
Resection of Solitary Liver Metastases with Pancreaticoduodenectomy
Amanjeet Singh, Tanveer
Singh, Adarsh Chaudhary
Department
of Surgical Gastroenterology, Sir Ganga Ram Hospital,
Rajinder Nagar. New Delhi, India
ABSTRACT
Context There is limited
information available about the feasibility and benefits of synchronous
resection of liver metastases in patients with pancreatic and periampullary
cancer undergoing pancreaticoduodenectomy. Objective We report on our
experience with 7 such patients. Design Analysis of the prospective
database was carried out to identify patients who underwent synchronous
resection of liver metastases with pancreaticoduodenectomy. Patients
Two-hundred and thirty patients underwent pancreaticoduodenectomy for
pancreatic and periampullary cancer in our unit between September 2003 and
September 2009. Main outcome measures The primary aim of our study was
to determine the survival benefits and the secondary aim was to evaluate their
safety and influence on the results of a pancreaticoduodenectomy. Results
Seven patients (3%) underwent synchronous resection of a solitary liver
metastasis. In these patients, the operative time and intra-operative blood
loss was marginally high as compared to the overall cohort of patients
undergoing pancreaticoduodenectomy; however, the complication rates and the
duration of the hospital stay were not affected. In patients undergoing
resection of liver metastasis, there were 4 recurrences over a mean follow-up
of 21 months. Conclusions In patients with resectable pancreatic and
periampullary cancer, the resection of a solitary liver metastasis can safely
be performed together with a pancreaticoduodenectomy; however, its impact on
improving survival has yet to be proven.
INTRODUCTION
Surgery
is the treatment of choice for pancreatic and periampullary cancer. With
improvements in surgical techniques and better perioperative management, the
morbidity and mortality of a pancreaticoduodenectomy has decreased. With these
encouraging developments, the limits of pancreaticoduodenectomy are being
stretched. Data about multivisceral resections
together with a pancreaticoduodenectomy are being published. Though the benefits
of such major procedures have yet to be conclusively proven, it is evident that
they can safely be performed in experienced centers [1, 2].
In
patients being considered for pancreaticoduodenectomy, despite all relevant
preoperative investigations, at laparotomy, it is not unusual to find
unexpected peritoneal or liver metastases. Confronted with a solitary liver
metastasis in an otherwise resectable tumor, it is difficult to decide on the
appropriate management. A choice has to be made between abandoning the plan for
radical surgery and resorting to a palliative bypass, performing a
pancreaticoduodenectomy and leaving the liver metastasis to be treated by
adjuvant chemotherapy or considering synchronous resection of the liver lesion
together with a pancreaticoduodenectomy. Information in the available
literature is inadequate to decide upon the best option. It has now been well
established that a subgroup of patients with liver metastases from colorectal
cancers benefit from surgical resection. These results induced a paradigm shift
in the management of liver metastases. Traditionally, liver resection for
colorectal liver metastases has been performed as a separate procedure from colectomy or rectal excision. But, recently, there have
been reports of a concomitant resection of liver metastasis with colonic
resection with good results [3, 4, 5, 6]. Experience
with surgery for liver metastases from pancreatic or periampullary cancer is
limited and, as expected, experience with synchronous resection together with a
pancreaticoduodenectomy is limited to a few patients only [7, 8, 9]. We report
on our experience of synchronous resection of liver metastases together with
pancreaticoduodenectomy.
PATIENTS
AND METHODS
Analysis
of our prospective database of patients undergoing pancreaticoduodenectomy for
pancreatic and periampullary cancer between September 2003 and September 2009
was carried out in order to identify patients who underwent synchronous
resection of an isolated liver metastasis. Two-hundred and thirty patients were
identified. These included 170 (73.9%) males and 60 (26.1%) females with a mean
age of 53.6±11.8 years (range: 18-80 years).
Preoperative
staging in our protocol included a contrast-enhanced computed tomographic scan.
Diagnostic laparoscopy was not a part of our staging procedure. All patients
being considered for synchronous liver resection were evaluated with
intraoperative ultrasound to rule out any other liver metastases which could
have been missed on palpation.
Synchronous
liver resection was performed only if a R0 resection of the pancreatic or
periampullary tumor was possible. We aimed at achieving at least a one
centimeter circumferential margin while attempting resection of the liver
metastases. Resection of the primary tumor was performed first and only then
resection of the liver metastasis attempted. This was done to avoid an
unnecessary liver resection if a complete resection of the primary tumor was
not possible. The reconstruction was performed as a final step so that, if a
Pringle maneuver was required to control bleeding during the liver resection,
it would not affect the integrity of the various anastomoses due to venous congestion.
All
postoperative complications were recorded. Standard definitions as proposed by
the International Study Group on Pancreatic Fistula (ISGPF) were used for
evaluating complications [10]. Patients operated on after May 2005 were prospectively analyzed using ISGPF criteria while
patients undergoing surgery before this period were retrospectively analyzed as
per these criteria. The length of the hospital stay was considered to be from
the first postoperative day until discharge from the hospital. Death during the
same hospital stay or within 30 days of surgery was considered as operative
mortality.
The
primary aim of our study was to determine the survival benefits of such
procedures and the secondary aim was to evaluate their safety and influence on
the results of pancreaticoduodenectomy.
ETHICS
Since
it was a retrospective analysis of data, consent was not obtained as per our
institutional research committee policy. The patients were managed according to
the ethical guidelines of the "World Medical Association Declaration of
Helsinki - Ethical Principles for Medical Research Involving Human
Subjects" adopted by the 18th WMA General Assembly, Helsinki,
Finland, June 1964, as revised in Tokyo 2004.
STATISTICS
Data
are reported as means, standard deviations and frequencies. The median
follow-up time was also evaluated. The Fisher’s exact and the Student’s t tests
were applied when appropriate by using the SPSS statistical package (version
13.0 for Windows; SPPS Inc., Chicago, IL, USA). Two-tailed P values less than
0.05 were considered statistically significant.
RESULTS
Eleven (4.8%) out
of 230 patients undergoing pancreaticoduodenectomy for pancreatic and
periampullary cancer were detected to have isolated liver metastases. Seven of
these were diagnosed preoperatively on CT scan while four were diagnosed
intraoperatively. Synchronous resection was not considered in four patients:
two with locally advanced tumors (both had a diagnosis of liver metastases on
preoperative CT) and another two with multiple liver metastases seen on
intraoperative ultrasound (both had intraoperative detection of liver
metastases). Seven patients (3.0%) underwent synchronous resection of the
isolated liver metastasis together with a pancreaticoduodenectomy. Four of
these patients had periampullary cancer while three underwent
pancreaticoduodenectomy for pancreatic cancer. Liver metastasis was located in
the left lobe in three patients while it was in the right lobe in four
patients. Resections were in the form of left lateral segmentectomies
in two patients and metastasectomy in five patients
(Table 1). All seven patients underwent a classic Whipple procedure with a
single loop reconstruction and a duct to mucosa pancreaticojejunostomy.
Table 1. Details of the
seven patients undergoing synchronous resections of a solitary liver
metastasis with pancreaticoduodenectomy for pancreatic and periampullary
cancer. |
|||||||
ID |
Age |
Sex |
Primary disease |
Location of
metastases |
Procedure |
Perioperative
complications |
Follow-up |
#1 |
44 |
Male |
Periampullary
cancer |
Segment II |
Left lateral segmentectomy |
None |
Alive at 48 months |
#2 |
58 |
Male |
Pancreatic head
cancer |
Segment VIII |
Metastasectomy |
None |
Died at 18 months
(local recurrence) |
#3 |
66 |
Male |
Periampullary
cancer |
Segment IV |
Metastasectomy |
Delayed gastric
emptying |
Died at 9 months
(liver metastases) |
#4 |
46 |
Male |
Periampullary
cancer |
Segment III |
Left lateral segmentectomy |
None |
Alive at 60 months |
#5 |
39 |
Male |
Periampullary
cancer |
Segment VIII |
Metastasectomy |
None |
Alive at 16 months |
#6 |
56 |
Female |
Pancreatic head
cancer |
Segment IV |
Metastasectomy |
None |
Died at 7 months
(liver metastases) |
#7 |
49 |
Male |
Pancreatic head
cancer |
Segment VI |
Metastasectomy |
None |
Died at 14 months
(local recurrence) |
The
histopathological examination of the resected specimens revealed adenocarcinoma
in all patients with negative resection margins for both the primary and
metastatic lesions. One patient had delayed gastric emptying which was resolved
with conservative management. There was no operative mortality in these 7
patients. Though the operative time (420±41 min vs. 362±36 min;
P<0.001) was significantly longer and the intraoperative blood loss (372±75
mL vs. 320±84 mL; P=0.107) was only marginally elevated as compared to
the other 223 patients undergoing pancreaticoduodenectomy, the overall
complication rate (3/7, 42.9% vs. 73/223, 32.7%; P=0.687) and the
duration of the hospital stay (9.7±4.8 days vs. 9.4±5.1 days; P=0.878)
were comparable. None of the seven patients undergoing synchronous resection
required perioperative blood transfusion versus 21 (9.4%) of the other
223 patients (P=1.000). All patients who had synchronous liver resections
received chemotherapy versus 134 (60.1%) of the other 223 patients undergoing
pancreaticoduodenectomy (P=0.576).
Over
a mean follow-up of 24.6±20.8 months (median: 16 months; range: 7-60 months),
there were four recurrences in patients undergoing synchronous resection of a
liver metastasis (57.1%); two of them were in the liver and two had a
locoregional recurrence. Three patients are disease free at follow-up times of
16, 48 and 60 months (Table 1).
DISCUSSION
The
presence of liver metastases in abdominal malignancies has been regarded to be
a sign of disseminated disease with a poor outcome. In recent years, this
pessimistic view has undergone some change with evidence of good results of
surgical resection in selected patients with colorectal liver metastases.
Interest in the surgical treatment of liver metastasis started with the premise
that the liver forms the first filter for the colorectal region; therefore,
patients with colorectal cancer with metastasis confined to the liver may not
have disseminated disease in contrast to patients with hematogenous metastases.
Good results of surgical treatment for colorectal liver metastases led to
surgery also being recommended for liver metastases from non-colorectal primary
tumors. Meaningful prolongation of survival has also been achieved in these
patients also [11, 12]. Pancreatic and periampullary cancer, such as colorectal
cancer, also drain into the portal system, and the liver is one of the most
common organs to be affected by these tumors. Surgical resection of liver
metastases from these tumors has not generally been acceptable. This is
because, biologically, pancreatic and periampullary tumors are inherently
aggressive with poor long-term survival especially in patients with pancreatic
cancer. Moreover, the required surgical procedure for these tumors, i.e. pancreaticoduodenectomy,
itself carries significant morbidity and possible mortality. Combining another
procedure, such as a liver resection, with pancreaticoduodenectomy makes it a
formidable proposition. These are the possible factors for withholding the use of
resectional surgery in hepatic metastasis from pancreatic and periampullary
tumors. In colorectal cancer, the availability of newer chemotherapies has also
contributed to improving both the resectability and the survival rates.
Chemotherapy has yet to show similar promise in pancreatic cancer.
As
already mentioned, with a definite decrease in mortality and a reduction in
morbidity associated with pancreaticoduodenectomies, data are emerging
regarding the potential benefits of multivisceral
resections in locally advanced pancreatic cancer. In a recent study, 19
patients underwent additional organ resections together with a
pancreaticoduodenectomy in the form of a right hemicolectomy in 12, right
nephrectomy in 2, liver resections in 2 and a combination of colon, kidney,
adrenal and small bowel resection in 3 patients. There was no significant
difference in the complication rates, and the authors concluded that additional
organ resections can be performed without any significant added morbidity [2]. Multivisceral resections for pancreatic malignancies have
been shown to be safe and have survival rates comparable to standard resections
[13]. There have been reports of long-term survivors of pancreatic cancer (more
than 5 years) undergoing pancreatectomies, and a multicentre study has
concluded that long-term survival after pancreatic cancer is a reality after R0
resections, even with advanced disease [14]. There is still a paucity of
evidence regarding the benefits of surgery in patients with metastatic liver
disease associated with pancreatic and periampullary cancer. In a study
involving 16 patients with synchronous and 7 patients with metachronous
resections of a solitary liver metastasis of pancreatic and periampullary
cancer, Klempnauer et al. [15] showed a median
survival time of 8.3 months after synchronous and 5.8 months after metachronous
hepatic resections with one-year survival rates of 41% and 40%, respectively.
The authors concluded that, although distant metastases are a definite sign of
advanced tumor stage, the prognosis of patients with hepatic metastases should
not be uniformly considered hopeless. Shrikhande et
al. [9] have also published their experience with synchronous resection of
liver metastases in pancreatic cancer in 11 patients. They reported a median
survival of 11.4 months in the synchronous resection group as compared to 5.9
months in patients undergoing exploratory laparotomy with or without a
palliative bypass. The morbidity and mortality of synchronous liver resection
with pancreaticoduodenectomy was comparable to patients undergoing
pancreaticoduodenectomy alone. In a systematic review of patients undergoing
synchronous resections of liver metastases together with
pancreaticoduodenectomy, 103 patients were included from three case reports and
18 studies involving fewer than 10 patients; it appeared that liver metastasis
resection for locally resectable pancreatic cancer can be performed in selected
cases with low morbidity and mortality. Overall survival in cases with only one
or a few liver metastases resected concomitantly with a pancreaticoduodenectomy
seemed to be comparable to cases undergoing pancreaticoduodenectomy without
evidence of metastasis [16]. On the contrary, Gleisner
et al. [17] have questioned the benefits of synchronous liver resections
together with pancreaticoduodenectomy in patients presenting with isolated
liver metastases detected intra-operatively in pancreatic and periampullary
cancer. In their experience with 22 patients, out of which 15 had periampullary
or pancreatic head cancer, they demonstrated that aggressive surgical resection
combining resection of the primary lesion with liver resection for these
patients yielded an overall survival rate similar to a palliative bypass alone,
yet with increased morbidity, hospital stay and, perhaps, mortality. They preferred
performing a palliative bypass on these patients as it appeared to be
associated with less morbidity and might have expedited postoperative recovery
and institution of systemic chemotherapy. There was no difference in survival
between pancreatic (median 5.9 months) and non-pancreatic (median 9.9 months)
primary tumor histology in patients who underwent synchronous resection for
liver metastases (p=0.43).
We performed
resection of the liver metastasis together with a pancreaticoduodenectomy with
the expectation that a possible R0 resection might benefit patients with
resectable tumors. Confirmation that the metastasis in the liver was isolated
was made intraoperatively by using intraoperative ultrasound. It was our belief
that merely carrying out a palliative bypass would be unfairly depriving the
patient of possible prolongation of survival and we were reluctant to rely on
chemotherapy alone to manage the liver metastasis, mainly because, in the event
of a complication developing after pancreaticoduodenectomy, chemotherapy would
be delayed or not used at all. The three patients in our series who have
survived had surgery performed for periampullary tumors; all 3 patients with
pancreatic cancer died. It could be that, since periampullary cancer has also
traditionally been shown to have a better prognosis as compared to pancreatic
head cancer, this could indicate that periampullary cancer might be a better
candidate for synchronous resection of liver metastases. On follow-up, only two
of our patients had recurrence of disease in the liver while, in the remaining
five patients, the liver was free of disease until death or until the last
follow-up. Though the numbers in our study are too small to have any definitive
correlation, it appears that, in centers with liver and pancreatic surgery
experience, minor liver resections can be safely performed together with a
pancreaticoduodenectomy without adding any additional morbidity or mortality.
Though the operative time may be prolonged and the complexity of the surgery
increased, the overall complication rates remain unaffected. The addition of a metastasectomy or left lateral segmentectomy
does not increase blood loss enough to necessitate the need for blood
transfusion. Though weak, there is some evidence to suggest a poorer long-term
outcome in patients with pancreatic cancer who receive an intraoperative blood
transfusion [18]. We hope our experience contributes to developing heightened
awareness regarding the possible potential of aggressive surgery in this
complex clinical situation and stimulates the start of a larger multicenter
study.
Received
May 7th, 2010 - Accepted June 18th, 2010
Keywords Adenocarcinoma;
Hepatectomy; Neoplasm Metastasis; Pancreatic Neoplasms; Pancreaticoduodenectomy
Abbreviations ISGPF:
International Study Group on Pancreatic Fistula
Conflict
of interest
The authors have no potential conflict of interest
Correspondence
Adarsh
Chaudhary
Room No 2208A
Department of Surgical Gastroenterology
Sir Ganga Ram Hospital
Rajinder Nagar
New Delhi
India 110060
Phone: +91-11.225.2226, +91-981.030.1847
Fax: +91-11.4225.2224
E-mail: adarsh_chaudhary@yahoo.com
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