Background
Pancreatic metastases represent an unusual clinical presentation. Sperti
et al, in a literature review of 2044 reported pancreatic resections, found that only 46 (1.4%) were performed for secondary tumors [
1]. Interestingly, the prevalence of metastases to the pancreas at autopsy is reported to be as high as 11%; the majority of these occur in patients with disseminated intraabdominal metastases [
2]. Tumors that most commonly metastasize to the pancreas by blood-borne dissemination include renal cell carcinoma, melanoma, and breast and lung carcinomas. Colon carcinoma may involve the pancreas by direct invasion [
3]. Up to 50% of patients with metastatic lesions are asymptomatic, the metastasis being detected upon routine surveillance for the primary tumor [
3]. The differential diagnosis of metastases to the pancreas as compared to primary pancreatic tumors can be difficult. The presence of multiple hypervascular lesions on imaging studies suggests pancreatic metastasis (whereas primary pancreatic tumors are commonly hypovascular), but primary neuroendocrine tumor of the pancreas must be ruled out [
3].
It is well documented that resection of hepatic metastases from colorectal carcinoma, sarcoma, or renal cell carcinoma achieves good survival. Similarly, resections of metastatic disease to the lungs and brain are now routinely undertaken. However, guidelines for pancreatic resection for metastatic disease remain unclear, probably due to the rarity of these tumors. While some recommend resection of pancreatic metastases only when there is no evidence of extrapancreatic disease [
4], others maintain that the presence of extrapancreatic disease is not a contraindication, provided that complete resection can be achieved [
1,
5].
Previous reports of small numbers of patients undergoing pancreatic resection for metastatic lesions have demonstrated median overall survivals of 19–42 months. Selected patients, particularly those with renal cell carcinoma, can achieve long-term survival [
1,
3,
5‐
11]. These results, along with the decreased morbidity and mortality of pancreatic resection currently obtained in experienced centers, support the aggressive management of pancreatic metastases in selected patients.
We report herein our single-institution experience with 29 pancreatic resections for non-primary lesions of the pancreas, including metastases to the pancreas from previously resected primaries, as well as intraabdominal tumors with direct extension to the pancreas. We sought to determine the morbidity and mortality of pancreatic resection in patients with nonpancreatic malignancies and to identify factors predictive of overall survival.
Discussion
Herein we report one of the largest single-institution experiences with pancreatectomy for locally advanced or recurrent non-pancreatic tumors. The majority of these operations were undertaken with curative intent, complete (i.e. R0) resection being achieved in 77%. Palliative pancreatectomy, however, did not result in complete tumor clearance in any patient, and was associated with poorer survival. While perioperative mortality was rare (one patient), morbidity was substantial, reflecting the magnitude of the operations performed.
The patient population in this study was somewhat younger than typical patients undergoing pancreatectomy for pancreatic cancer, reflecting our willingness to pursue more aggressive surgical approaches in young, healthy patients. However, age was not a predictor of outcome. The majority of pancreatectomies were performed for cancers of gastrointestinal origin (most commonly colorectal carcinoma), and often for locally advanced disease. Metachronous spread of disease to the pancreas most commonly was of renal origin, as has been demonstrated previously [
3,
8‐
11]. Non-gastrointestinal primaries conferred improved overall survival as compared to gastrointestinal primaries, regardless of the completeness of resection.
In this study, we observed a median overall survival of 12 months. This is less than the survival rates reported in previous studies [
1,
3,
5‐
11]. There are several possible explanations for this finding. Many previous reports of resection of pancreatic metastases include patient populations that were primarily or exclusively composed of patients with renal cell carcinoma. It is well known that metastases from renal cell carcinoma may present at a prolonged interval after resection of the primary, and that long-term survival of up to 10 years after resection of the metastatic lesion is often achieved [
8‐
11]. Although there were five patients in our series with renal cell carcinoma, most patients had GI malignancies, which are generally characterized by shorter disease-free interval and more aggressive tumor biology. In addition, our series included 12 patients (41%) who had R1 or R2 resections.
Several recent reports have demonstrated the utility of resection of colon carcinoma en bloc with pancreaticoduodenectomy for locally advanced disease [
14‐
18]. Kama
et al detailed the outcome of four patients who underwent en bloc pancreaticoduodenectomy with right hemicolectomy (plus resection of liver segments V and VI in one patient) for locally invasive right colon cancer [
14]. There was one postoperative mortality but the remaining three patients had disease-free survival of 14–41 months. Berrospi
et al studied three patients having en bloc resection for colon cancers involving the pancreas and duodenum; all were alive without evidence of disease at 10, 30, and 113 months, respectively [
15]. Similarly, reports by Koea and Curley upon 8 and 12 patients, respectively, undergoing extended resections for colon carcinomas invading the duodenum or pancreatic head revealed low mortality and extended survival [
16,
17]. Finally, Kapoor
et al recently evaluated their experience of 11 patients undergoing en bloc resection of adjacent organs for right colon cancer: six had en bloc pancreaticoduodenectomy; three, en bloc local excision of duodenal wall; one, en bloc resection of segments V and VI of the liver; and one, en bloc distal gastrectomy [
18]. Median disease-free survival among this group of patients was 54 months. These results suggest that there may be a subgroup of patients with colorectal carcinoma, particularly right colon carcinoma, who have locally invasive disease involving the duodenum or pancreas that responds well to aggressive resection.
Many of the reports in the literature of resection for pancreatic metastases or primaries with extension to the pancreas include only those patients with margin-negative resections. For example, Pingpank
et al, reported on a population of 35 patients with similar distribution of primary tumor histologies to that reported in this study [
19]. However, only patients with negative margins were included. Median overall survival of 46 months was achieved. In contrast, the report by Z'Graggen
et al, included 6 of 10 patients who underwent palliative procedures only [
6]. In this study, a median overall survival of 19 months was observed. Thus, the lower overall survival observed in our study may possibly be explained by both the predominance of patients with GI primaries, and the fact that patients undergoing R1 or R2 resections were included. In order to truly understand the risks and benefits of pancreatectomy for non-pancreatic tumors, we felt it necessary to include all patients undergoing pancreatectomy, including those who had R1 or R2 resection.
As such, we demonstrated that R0 resection, as compared to R1 or R2, in addition to non-GI primary versus GI primary, provided statistically better survival. A univariate analysis showed R0 resection, non-GI primary, and resection of metastatic disease to the pancreas versus en bloc excision for extension to the pancreas to be predictors of survival. However, only R0 resection was predictive of survival by multivariate analysis. This result again emphasizes the fact that complete resection of metastatic or locally advanced lesions must be achieved in order to affect survival.
Competing interests
The author(s) declare that they have no competing interests.
Authors' contributions
KV participated in data acquisition and interpretation, wrote the manuscript, and critically reviewed the manuscript. PM participated in data acquisition. KW participated in data acquisition (chart review). ECE participated in data acquisition and critically reviewed the manuscript. MB designed the study, participated in data acquisition and interpretation, and critically reviewed the manuscript. All authors read and approved the final manuscript.