Annals of Surgical Oncology Sign the Guestbook
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
10.1245/s10434-006-9131-8
Annals of Surgical Oncology 14:118-127 (2007)
© 2007 Society of Surgical Oncology
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Shrikhande, S. V.
Right arrow Articles by Büchler, M. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shrikhande, S. V.
Right arrow Articles by Büchler, M. W.

Original Article

Pancreatic Resection for M1 Pancreatic Ductal Adenocarcinoma

Shailesh V. Shrikhande, MD1, Jörg Kleeff, MD2, Carolin Reiser, MD2, Jürgen Weitz, MD2, Ulf Hinz, MSc2, Irene Esposito, MD3, Jan Schmidt, MD2, Helmut Friess, MD2 and Markus W. Büchler, MD2

1 Department of Gastrointestinal Surgical Oncology, Tata Memorial Hospital, Ernest Borges Marg, Parel, Mumbai, 400012, India
2 Department of General Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany
3 Institute of Pathology, University of Heidelberg, Im Neuenheimer Feld 220, 69120 Heidelberg, Germany

Correspondence: Address correspondence and reprint requests to: Markus W. Büchler, MD; E-mail: markus_buechler{at}med.uni-heidelberg.de


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: Improved safety of pancreatic surgery has led to consideration of more aggressive approaches, such as resection for primary pancreatic ductal adenocarcinoma (PDAC) with metastatic disease (M1).

Methods: A total of 29 patients who underwent pancreatic resection with resection of associated metastatic disease (interaortocaval lymph node dissection, liver resection, and/or multiorgan resections) were retrospectively identified from a database of 316 R0/R1 pancreatic resections for PDAC. An explorative data analysis of perioperative and clinicopathological parameters, and overall survival was performed by Kaplan-Meier estimation, log rank test, and Fisher’s exact test.

Results: The overall in-hospital mortality and morbidity of R0/R1 pancreatic resections for M1 disease (n = 29) was 0% and 24.1%, compared with 4.2% and 35.2% of R0/R1 pancreatic resections for M0 disease (n = 287). The median overall survival time was 13.8 months (95% confidence interval [CI], 11.4–20.5), and the estimated 1-year overall survival rate was 58.9% (95% CI, 34.8–76.7) for patients with M1 disease. The median survival in those with metastatic interaortocaval lymph nodes was 27 months (95% CI, 9.6–27.0), whereas it was 11.4 months (95% CI, 7.8–16.5) and 12.9 months (95% CI, 7.2–20.5) for those with liver and peritoneal metastases, respectively.

Conclusions: Pancreatic resections with M1 disease can be performed with acceptable safety in highly selected patients. The survival after interaortocaval lymph node resection is comparable to that of other lymph nodes that do not constitute M1 disease. Resection of liver and peritoneal metastases, although safe in this series, cannot be generally recommended until further controlled trials can be conducted.

Key Words: Pancreatic cancer • Resection • Metastatic disease • Survival • Liver metastasis • Interaortocaval lymph node metastasis


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Pancreatic cancer is the fourth leading cause of cancer-related deaths in Europe and the United States, with approximately 75,000 and 32,000 deaths per year, respectively. It carries a dismal prognosis: its mortality rate nearly equals its incidence of 11 patients per 100,000 population.1–3 Despite tremendous advances in oncology over the last few decades, clinicians and researchers have struggled to alter the inherently aggressive behavior of pancreatic cancer. Although advances in molecular biology are expected to aid development of effective chemotherapy and tumor-targeted therapy, surgery remains the gold standard against which all new treatment options continue to be evaluated.4 Techniques and outcome of resectional surgery for pancreatic cancer have gradually improved over the years.5,6

During the last decades, many institutions have reported reduced hospital mortality rates (< 5%), and some large series from centers with extensive experience in pancreatic resections reported no mortality.7,8 Clearly, resectional surgery for pancreatic cancer has reached a new level of safety. The 5-year survival has also slightly improved; this might possibly be due to a combination of earlier detection, improved quality of surgical resections, and more effective adjuvant treatment modalities.9,10

In the background of these results, and with a lack of availability of other, newer and better treatment options on the horizon, more extensive surgical resections are logically being considered in the hope of offering improved survival and even a better quality of life.11–14 Although several series have evaluated extended lymphadenectomy and vascular resection for locally advanced pancreatic and periampullary cancer,15–18 little information exists about outcomes after pancreatic resection for pancreatic ductal adenocarcinoma (PDAC) (excluding other periampullary pathologies) when the patient has metastatic disease (M1 disease status). This is largely because presence of distant metastasis in pancreatic cancer is considered to be a contraindication for surgery; yet this group accounts for most cases.19 Nonetheless, there are occasions when a pancreatic resection with resection of metastatic disease is undertaken inadvertently (retrospective diagnosis after final histopathology confirmation) or in special circumstances (e.g., a fit patient in good general condition, American Society of Anesthesiologists [ASA] grade III or less, impression of low overall tumor burden, patient insistence).

This study was carried out to evaluate the outcomes in this uncommon group of patients treated in a high-volume tertiary referral center of pancreatic surgery.


   PATIENTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
A total of 29 patients who underwent complete pancreatic resection with resection of associated metastatic disease were retrospectively identified from a prospectively maintained database of 550 consecutive explorations for primary PDAC that were undertaken between October 2001 and July 2005 at the Department of Surgery, University of Heidelberg. In 316 cases, a macroscopic complete (R0/R1) resection of the tumor was achieved. A total of 287 were treated by R0/R1 resection for M0 disease, and 29 patients (9.1%) underwent R0/R1 resection for M1 disease (according to the 2002 International Union Against Cancer classification). A total of 193 of the 550 operated tumor were diagnosed as M1 tumor. Therefore, these 29 R0/R1 resections for M1 disease accounted for only 15.0% of the total number of M1 tumor. A total of 164 patients with M1 disease, 118 of whom had liver metastasis only, did not undergo any resection (i.e., exploration only or palliative bypass). Of the remaining 70 patients, 29 underwent R2 resections for M0 disease, and 41 underwent exploration for locally advanced M0 disease. For histopathological analysis, the resection margins of the pancreas, its posterior surface, and the resections margins of the stomach or proximal duodenum, distal duodenum, or jejunum, and bile duct were investigated. R1 was defined as tumor infiltration into these margins. In the later study period, soft tissue margins (which in a partial duodenopancreatectomy are classified as anterior, medial, posterior, and superior) were inked and then examined. However, in the present study, only the first definition was used.

In the R0/R1M1 group, there were 11 men and 18 women. The median age was 65 years, with an interquartile range (IQR) of 60 to 74 years. Seventeen patients were classified as ASA grade 2 and 11 as grade 3, and the grade of one patient could not be identified from in hospital records.

The disease stage after resection (tumor, node, metastasis system [TNM]), the site of metastatic disease (M1 disease), the indication for resection in those situations were M1 disease status was known, the duration of hospitalization after surgical resection, details of any adjuvant therapy, short-term outcome after surgical resection, and long-term survival after hospital discharge were prospectively documented.

Only classical primary cases of PDAC were evaluated, and all other periampullary pathologies were excluded. Furthermore, data of 287 patients with R0/ R1 M0 disease and of 118 patients not treated with resection but harboring M1 (only liver) disease were evaluated for purposes of comparison with the main study group.

Statistical Analysis
SAS software, release 9.1 (SAS Institute, Inc. Cary, NC), was used for statistical analysis. The distribution of age at operation, blood loss, and postoperative hospital stay and follow-up time were described as median with an IQR. Comparisons between subgroups of patients were performed with Fisher’s exact test. Kaplan-Meier estimations were used to analyze the overall survival from the date of surgery. The 1-year survival rate and the median survival time with the corresponding 95% confidence intervals (CIs) were presented. Patients alive at the last follow-up were censored. The end of the follow-up period for all patients alive was December 2005. No patient was lost to follow-up. The log rank test was performed to compare survival time distributions between curves regarding site of metastatic disease. Two-sided P values were always computed, and an effect was considered statistically significant at P ≤ .05.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
None of the patients was proven to be harboring metastatic disease in the preoperative evaluation. In 14 patients, metastatic disease was identified or suspected intraoperatively before resection, whereas in the remaining 15 patients, metastatic disease was diagnosed retrospectively only after final histopathologic reporting. The indications for resection despite intraoperative knowledge of metastatic disease were: patient considered to be in good general condition, patient preference for resection despite preoperative counseling regarding possibility of metastatic disease, resection of peripherally located one or two isolated liver metastases, the impression of "low overall tumor burden," a high probability of R0 resection, and an ASA grade of III or better. With regard to interaortocaval lymph nodes, no intraoperative frozen section examination was undertaken to confirm presence of M1 disease, and patients were only subjected to resection provided R0 status could be achieved with some degree of certainty. This premise ensured that results of frozen section examination would be inconsequential from the point of altering operative strategy. Interaortocaval lymph node dissection was not carried out routinely, but only when there was intraoperative suspicion of metastatic spread to these nodes.

Although 18 patients underwent pancreaticoduodenectomy for pancreatic head cancer, 9 patients underwent distal pancreatectomy for pancreatic body and tail cancer, and 2 patients underwent total pancreatectomy for locally advanced pancreatic head cancer.

Three of the 18 who underwent pancreaticoduodenectomy had solitary metastasis to the liver. Although these three underwent single segmentectomies, a fourth patient underwent resection of segments 7 and 8 for two separate, isolated, peripherally located lesions. Nine other patients of the 18 who underwent pancreaticoduodenectomy had metastatic disease to the interaortocaval group of lymph nodes. The remaining 5 of the 18 patients who underwent pancreaticoduodenectomy had metastatic peritoneal nodules (colonic mesentery n = 2; and peritoneum lining the abdominal wall n = 3). Six of the nine patients who underwent distal pancreatectomy had metastatic disease to the liver. Although four were subjected to segmentectomies for solitary lesions, two underwent resections of segments 4b, 6, and 7 and segments 2 and 8, respectively, for two separate isolated lesions. One out of these six patients had meta-static disease to the interaortocaval group of lymph nodes along with a solitary liver metastasis. The other three patients who underwent distal pancreatectomy had metastatic peritoneal nodules. One of the two patients who underwent total pancreatectomy had metastatic disease to the liver. That patient underwent a liver segment resection, whereas the other had metastatic disease to the interaortocaval group of lymph nodes. The numbers of different surgeries with various M1 disease resections are listed in Table 1Go. The primary tumor, site of metastasis, TNM staging, type of surgery performed, and survival are listed in Table 2Go, and intraoperative photographs after some of these resections are provided in Fig. 1Go.


View this table:
[in this window]
[in a new window]

  		TABLE 1. Numbers of different surgeries and indicated sites of metastasis
 

View this table:
[in this window]
[in a new window]

  		TABLE 2. Primary tumor, site of metastasis, tumor, node, metastasis system (TNM) staging (UICC 2002), type of surgery, and survival
 

Figure 1
View larger version (128K):
[in this window]
[in a new window]

  		FIG. 1. (A) Radical resection for pancreatic head cancer. Inset: nonanatomical resection of the liver segment 3 for solitary metastasis. (B) Aortic patch and sutured vena cava after resection of locally advanced pancreatic cancer. (C) Radical clearance of lymph nodes from the interaortocaval groove.

 
The median intraoperative blood loss for these resectional procedures with M1 disease was 600 mL (IQR, 400–1000 mL). When we compared this data with pancreatic resection for R0/R1 resected ductal adenocarcinoma with M0 disease, the figures were comparable with a median intraoperative blood loss of 700 mL (IQR, 500–1000 mL; not significant, P = .432). Seven patients developed postoperative surgical complications after these resections (24.1%). One patient developed delayed gastric emptying that settled down conservatively, and the patient was discharged on the postoperative day 19. Two patients developed an intra-abdominal abscess requiring interventional radiologic drainage; one patient had postoperative bleeding followed by delayed gastric emptying; and two patients developed a controlled pancreatic fistula. The surgical complication rate after pancreatic resection for M0 disease (24.4%) was thus slightly higher (but not statistically significantly) compared with pancreatic resection with M1 disease.

Two patients in this series, one with bleeding and the other with pancreatic fistula who developed signs of localized peritonitis, required relaparotomy (6.9%) on postoperative days 1 and 14, respectively. No obvious bleeding source was identified in the first patient, and the patient was closed after a thorough abdominal lavage. The patient with a pancreatic fistula received an abdominal lavage, and abdomen was closed after placement of intra-abdominal drains. Both of them recovered uneventfully and were discharged 16 and 9 days, respectively, after relaparotomy. In the group of pancreatic resections for M0 disease, a relaparotomy was required in 18 patients (6.3%). This difference was not statistically significant (P = .704) (Table 3Go). The median duration of hospitalization after these surgical resections for M1 disease was 12 days (IQR, 9–15 days) and also 12 days (IQR, 10–14 days) after pancreatic resections for M0 disease (not significant, P = .692). The 30-day perioperative mortality was 0% in our series; it was 4.2% for the group of patients who underwent R0/R1 resection for M0 disease. This difference was not statistically significant (P = .611). Comparative outcomes after resectional surgery for PDAC with M1 (n = 29) and M0 (n = 287) disease are listed in Table 3Go.


View this table:
[in this window]
[in a new window]

  		TABLE 3. Comparative outcomes after resectional surgery (R0/R1) for pancreatic ductal adenocarcinoma with M1 (n = 29) and M0 (n = 287) disease
 
One of the 29 patients received radiochemotherapy as neoadjuvant treatment. A total of 23 of 29 patients received adjuvant treatment in the form of radiochemotherapy (n = 1), administration of gemcitabine (n = 13, including two patients who received an experimental tumor vaccination), fluorouracil (n = 6), only experimental tumor vaccinations (n = 2), and adjuvant treatment, the details of which are not known (n = 1). None of the patients was part of any ongoing adjuvant treatment studies (with the exception of tumor vaccination) because of their M1 disease status. Six remaining patients did not receive any adjuvant treatment for various reasons, such as unsatisfactory general condition or patient unwillingness for treatment.

At the last follow-up, 12 patients were alive and 17 dead of disease. The median follow-up time of patients who were alive was 8.5 months (IQR, 7.1–11.6 months). The follow-up time ranged between 4.7 and 25.9 months. The estimated median overall survival time was 13.8 months (95% confidence interval [CI], 11.4–20.5), and the estimated 1-year overall survival rate was 58.9% (95% CI, 34.8–76.7) (Fig. 2Go). The estimated median survival time of the 23 patients who received adjuvant treatment was 15.8 months (95% CI, 11.4–20.5). Twelve patients were alive at last follow-up. Four of the six patients who received no adjuvant treatment died 6, 9, 9.5, and 13 months, respectively, after pancreatic resection. The survival time of the remaining two patients who were alive was 8.9 and 25.9 months, respectively. No difference was observed between both groups (P = .533). The estimated median survival time in the nine patients with metastatic disease to interaortocaval group of lymph nodes was 27 months (95% CI, 9.6–27.0) compared with an estimated median survival time in those with metastatic disease to liver (n = 11), and peritoneum (n = 9) of 11.4 months (95% CI, 7.8–16.5), and 12.9 months (95% CI, 7.2–20.5), respectively.


Figure 2
View larger version (7K):
[in this window]
[in a new window]

  		FIG. 2. Kaplan-Meier curve showing overall survival in patients with resectable pancreatic cancer with M1 disease. Patients alive at last follow-up are censored and indicated.

 
The difference between the three survival curves (interaortocaval lymph nodes, liver, and peritoneum) was not statistically significant (P = .145) (Fig. 3Go). Additionally, difference in survival curves between R0/R1 M1 (liver metastases) and M1 (liver metastases) without any resection (exploration/bypass) was statistically significant (P = .0384), with a median survival of 11.4 months (95% CI, 7.8–16.5) for the R0/R1M1 group compared with 5.9 months (95% CI, 5.4–7.6) for the M1 group (liver metastases) without any resection (Fig. 4Go).


Figure 3
View larger version (11K):
[in this window]
[in a new window]

  		FIG. 3. Kaplan-Meier curve showing survival in patients who have undergone resection for pancreatic cancer with interaortocaval lymph node, liver, and peritoneal metastasis (M1 disease). Patients alive at the last follow-up are censored and indicated.

 

Figure 4
View larger version (8K):
[in this window]
[in a new window]

  		FIG. 4. Kaplan-Meier curve comparing survival curve of R0/ R1M1 (liver metastases) with survival curve of patients with liver metastasis who did not undergo resection but exploration or palliative bypass procedures. Patients alive at the last follow-up are censored and indicated.

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Despite 5-year survival figures of only 10% to 20% after pancreaticoduodenectomy for PDAC of the pancreatic head,20 surgery is the only potentially curative treatment available in resectable pancreatic cancer. The overall survival rate for PDAC is determined by radicality of resection. In a series of 366 operated patients of pancreatic adenocarcinoma, our group reported an in-hospital mortality rate of 2.8% and an overall actuarial 5-year survival rate of 19.8% after resection.21 It was observed that survival was better after curative resection (R0) and in lymph node–negative patients. This observation has been confirmed by a number of large series. Yeo et al.22 reported a median survival of 18 months for 143 curatively resected patients, and the ESPAC-1 multicenter trial23 reported that disease-free margins (R0) resulted in a median survival of 16.9 months in 541 patients; this figure rose to 20.1 months with the addition of adjuvant chemotherapy.24 Unfortunately, the number of patients who can be offered a "true R0[rdquor] resection is small, and most patients with pancreatic adenocarcinoma will harbor occult or overt metastatic disease in the regional lymph nodes, surrounding structures, and the liver. As expected, the results deteriorate when R0 resections are performed with surrounding diseased lymph nodes. Richter et al.,25 reporting on a 25-year experience, observed that node-positive patients (n = 63) had a 19.9% 5-year survival (median survival, 15.5 months) compared with 37% in node-negative patients. Similarly, the ESPAC-1 trial recorded a 5-year survival of 25.5% in 246 node-negative patients; this figure was 9.3% in 277 node-positive patients for the entire study cohort.26

On the basis of our present understanding of the spread of pancreatic cancer, other treatment modalities, such as chemotherapy, radiotherapy, and, more recently, biologic agents, are constantly being evaluated to tackle this dismal scenario. The median survival of locally advanced unresectable pancreatic cancer is poor (10.5–15.7 months) (Table 4Go) and tends to get even worse in the setting of metastatic disease (5.6–9.5 months).19,27 Palliative chemotherapy, mainly in the form of gemcitabine monotherapy and its newer combination regimens, have so far provided only some benefit (Table 4Go).28,29 Recent phase 3 studies have suggested an improvement in survival of advanced pancreatic cancer when erlotinib or capecitabine are combined with gemcitabine, but further results are necessary to confirm the real benefit of these combinations.30,31 Thus, a modest overall survival benefit is possible, and median survival with palliative treatment was approximately 6.4 months for those treated with erlotinib and gemcitabine, compared with 5.9 months for those treated with gemcitabine alone. As regards capecitabine in combination with gemcitabine, 1-year survival was achieved in 24% patients who received this regimen compared with 19% patients who received gemcitabine alone.


View this table:
[in this window]
[in a new window]

  		TABLE 4. Survival after treatment for different stages of pancreatic cancer
 
Against this background, with curative resectional surgery for pancreatic cancer continuing to remain the gold standard, increasingly aggressive and extended resections aimed at distant diseased lymph nodes and even liver metastases have been attempted.32 They are an extension of the philosophy that because chemotherapy and other modalities offer limited survival benefit in patients with locally advanced and metastatic pancreatic cancer, some benefit may yet be possible in resectable pancreatic cancer with metastatic disease in highly selected patients. Furthermore, there are reports that favor radical surgery for pancreatic cancer, especially because the operative mortality is now low and because resection, even if only palliative (R2), is considered to potentially provide a better survival rate than mere bypass.33,34

However, the various outcomes after resection of involved lymph nodes that result in M1 staging are sparsely reported.35,36 The same holds true for situations where liver metastasis from pancreatic cancer has been resected;37,38 on the basis of a number of anecdotal reports, an objective conclusion is difficult to reach and treatment guidelines difficult to formulate. Our analysis reports that the intraoperative blood loss for these procedures (R0/R1 M1) was no different from those who underwent standard pancreatic resections (R0/R1 M0). Also, the hospital stay was comparable with a median of 12 days for both groups. Furthermore, although the overall in-hospital mortality of R0/R1 pancreatic resections with M0 disease at our center was 4.2%, the in-hospital and 30-day perioperative mortality in our subgroup was zero. These data clearly suggest that these major resections can be performed with acceptable safety even in patients with advanced pancreatic cancer. However, the comparable results for two diverse stages of pancreatic cancer are possible only as a result of a combination of careful patient selection, good nursing care, and the surgical expertise and confidence of a large-volume center.

There are several limitations of the present study that restrict the value of the conclusions. (1) Clearly, there is a selection bias in our series, inasmuch as the 29 patients were more likely to be in better general condition than patients resected for nonmetastatic disease. (2) The groups are rather heterogeneous with respect to the operation performed (Whipple, pylorus-preserving pancreaticoduodenectomy, distal, and total pancreatectomy) and the localization of meta-static disease (liver, interaortocaval lymph nodes, and peritoneum). (3) The M1 status was known only after the operation and pathohistologic analysis in some of the patients. (4) The study and analysis are retrospective in nature.

Irrespective of these limitations, our results show that it is possible to achieve a median survival of 13.8 months after R0/R1 surgery for advanced pancreatic cancer with M1 disease with a 1-year survival of 58.9%. Our results should be judged against the background that survival in advanced pancreatic cancer with metastatic disease is 10% at the end of 1 year1 (23% in our control group). Overall median survival with the best available palliative chemotherapy for nonresectable advanced pancreatic cancer is 4.4 to 10.2 months39–41 (Table 4Go), compared with resections with only local lymph node involvement, which results in a median survival of 15.5 to 16.1 months.21,25 The median survival of 13.8 months in our series has also to be judged against recent data of 1674 patients with pancreatic cancer who underwent resection in California between 1994 and 2000. The median survival in this group was 13.3 months, compared with 3.5 months for 10,612 patients that did not undergo resection.42

But why should patients with metastatic pancreatic cancer have improved survival after these extended resections? Possible reasons could be that even when resections are performed with curative intent, patients are likely to harbor occult local disease or distant metastases. Thus, pancreatic resections are mostly palliative,21,43 and resecting overt metastases might extend the scope of palliative pancreatic cancer surgery.

There was a difference between outcomes of patients resected for interaortocaval lymph node metastasis with extended lymphadenectomy (estimated median survival, 27 months) and those resected for liver and peritoneal metastasis (estimated median survival, 11.4 and 12.9 months, respectively). Our survival data of 27 months after resection of metastatic interaortocaval lymph nodes is somewhat different from the observation of Connor et al.44 that these patients fare worse than those without metastases to these nodes.21,44 In this context, interaortocaval lymph node metastases are present in only 10% to 20% in patients with pancreatic head cancer. Although it is now clear that routine extended lymphadenectomy has no benefit over standard lymphadenectomy,17,18,21,45–47 our results imply that if interaortocaval lymph nodes are involved (as confirmed by frozen sections), or if there is a strong suspicion of involvement, resection would be justified. We believe that interaortocaval lymph node involvement should not be considered a contraindication to resection, provided that the primary tumor is resectable with a degree of certainty.

On the other hand, although it may be justifiable to resect pancreatic head cancer with metastasis to interaortocaval group of lymph nodes, the same may not be true for those with liver metastasis. Klempnauer et al.,48 reporting in 1996 on 22 patients with hepatic metastases from pancreatic cancer, had reported a median survival of 8.3 months after synchronous and 5.8 months after metachronous hepatic resections and raised the possibility that individual patients with hepatic resections for M1 disease might gain valuable survival time. Their series, like ours, had recorded both R0 and R1 resections. Our survival results of 11.4 months for R0/R1M1 (liver) resections compare favorably to other palliative modalities currently available for treating advanced pancreatic cancer and also to our comparison group of M1 cases who did not undergo resection (Table 4Go). However, our numbers are small, thereby preventing any objective statistical comparisons.

In conclusion, resection of pancreatic cancer with concomitant resection of its associated metastatic disease can be performed safely without increased morbidity and mortality. Resection of metastatic disease in patients with pancreatic cancer undergoing resection can provide encouraging results and offer hope of prolonging life in selected patients. Irrespective of the inherent limitations of the study, our results suggest that aggressive surgery, especially for interaortocaval lymph node involvement, could be justified in these patients. However, the decision to resect metastatic disease, especially liver and peritoneal metastasis, should be made with great care after a thorough assessment of the overall risk-benefit ratio for the individual patient. Patients should also be counseled before surgery about the potential advantages and pitfalls of such a surgical exercise. Justification for resecting liver or peritoneal metastasis will depend on results of controlled trials. Pending these results, our experience could potentially represent the best currently available option in treating intraoperatively discovered metastatic but locally resectable pancreatic cancer in highly selected patients.


   FOOTNOTES
 
S.V.S. and J.K. contributed equally to this article.

Received for publication June 2, 2006. Accepted for publication June 22, 2006.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2006. CA Cancer J Clin 2006; 56:106–30.[Abstract/Free Full Text]
  2. Parkin DM, Bray FI, Devesa SS. Cancer burden in the year 2000. The global picture. Eur J Cancer 2001; 37(Suppl 8):S4–66.[Medline]
  3. Parkin DM, Bray F, Ferlay J, Pisani P. Estimating the world cancer burden: Globocan 2000. Int J Cancer 2001; 94:153–6.[CrossRef][Medline]
  4. Ozawa F, Friess H, Kunzli B, et al. Treatment of pancreatic cancer: the role of surgery. Dig Dis 2001; 19:47–56.[CrossRef][Medline]
  5. Fernandez-del CC, Rattner DW, Warshaw AL. Standards for pancreatic resection in the 1990s. Arch Surg 1995; 130:295–9.[Abstract/Free Full Text]
  6. Stojadinovic A, Hoos A, Brennan MF, Conlon KC. Randomized clinical trials in pancreatic cancer. Surg Oncol Clin N Am 2002; 11:207–29.[CrossRef][Medline]
  7. Cameron JL, Pitt HA, Yeo CJ, Lillemoe KD, Kaufman HS, Coleman J. One hundred and forty-five consecutive pancreaticoduodenectomies without mortality. Ann Surg 1993; 217:430–5.[Medline]
  8. Trede M, Schwall G, Saeger HD. Survival after pancreatoduodenectomy. 118 consecutive resections without an operative mortality. Ann Surg 1990; 211:447–58.[Medline]
  9. Howard JM. Development and progress in resective surgery for pancreatic cancer. World J Surg 1999; 23:901–6.[CrossRef][Medline]
  10. Picozzi VJ, Kozarek RA, Traverso LW. Interferon-based adjuvant chemoradiation therapy after pancreaticoduodenectomy for pancreatic adenocarcinoma. Am J Surg 2003; 185:476–80.[CrossRef][Medline]
  11. Fortner JG. Regional pancreatectomy for cancer of the pancreas, ampulla, and other related sites. Tumor staging and results. Ann Surg 1984; 199:418–25.[Medline]
  12. Fortner JG. "Radical" abdominal cancer surgery: current state and future course. Jpn J Surg 1989; 19:503–9.[CrossRef][Medline]
  13. Shoup M, Conlon KC, Klimstra D, Brennan MF. Is extended resection for adenocarcinoma of the body or tail of the pancreas justified?. J Gastrointest Surg 2003; 7:946–52.[CrossRef][Medline]
  14. Yeo CJ, Cameron JL, Sohn TA, et al. Pancreaticoduodenectomy with or without extended retroperitoneal lymphadenectomy for periampullary adenocarcinoma: comparison of morbidity and mortality and short-term outcome. Ann Surg 1999; 229:613–22.[CrossRef][Medline]
  15. Capussotti L, Massucco P, Ribero D, Vigano L, Muratore A, Calgaro M. Extended lymphadenectomy and vein resection for pancreatic head cancer: outcomes and implications for therapy. Arch Surg 2003; 138:1316–22.[Abstract/Free Full Text]
  16. Nguyen TC, Sohn TA, Cameron JL, et al. Standard vs. radical pancreaticoduodenectomy for periampullary adenocarcinoma: a prospective, randomized trial evaluating quality of life in pancreaticoduodenectomy survivors. J Gastrointest Surg 2003; 7:1–9.[CrossRef][Medline]
  17. Pedrazzoli S, DiCarlo V, Dionigi R, et al. Standard versus extended lymphadenectomy associated with pancreatoduodenectomy in the surgical treatment of adenocarcinoma of the head of the pancreas: a multicenter, prospective, randomized study. Lymphadenectomy Study Group. Ann Surg 1998; 228:508–17.[CrossRef][Medline]
  18. Yeo CJ, Cameron JL, Lillemoe KD, et al. Pancreaticoduodenectomy with or without distal gastrectomy and extended retroperitoneal lymphadenectomy for periampullary adenocarcinoma, part 2: randomized controlled trial evaluating survival, morbidity, and mortality. Ann Surg 2002; 236:355–66.[CrossRef][Medline]
  19. Van CE, Aerts R, Haustermans K, Topal B, Van SW, Verslype C. Systemic treatment of pancreatic cancer. Eur J Gastroenterol Hepatol 2004; 16:265–74.[CrossRef][Medline]
  20. Smeenk HG, Tran TC, Erdmann J, van Eijck CH, Jeekel J. Survival after surgical management of pancreatic adenocarcinoma: does curative and radical surgery truly exist?. Langenbecks Arch Surg 2005; 390:94–103.[CrossRef][Medline]
  21. Wagner M, Redaelli C, Lietz M, Seiler CA, Friess H, Buchler MW. Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinoma. Br J Surg 2004; 91:586–94.[CrossRef][Medline]
  22. Yeo CJ, Cameron JL, Lillemoe KD, et al. Pancreaticoduodenectomy for cancer of the head of the pancreas: 201 patients. Ann Surg 1995; 221:721–31.[Medline]
  23. Neoptolemos JP, Stocken DD, Dunn JA, et al. Influence of resection margins on survival for patients with pancreatic cancer treated by adjuvant chemoradiation and/or chemotherapy in the ESPAC-1 randomized controlled trial. Ann Surg 2001; 234:758–68.[CrossRef][Medline]
  24. Neoptolemos JP, Stocken DD, Friess H, et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 2004; 350:1200–10.[Abstract/Free Full Text]
  25. Richter A, Niedergethmann M, Sturm JW, Lorenz D, Post S, Trede M. Long-term results of partial pancreaticoduodenectomy for ductal adenocarcinoma of the pancreatic head: 25-year experience. World J Surg 2003; 27:324–9.[CrossRef][Medline]
  26. Bassi C, Stocken DD, Olah A, et al. Influence of surgical resection and post-operative complications on survival following adjuvant treatment for pancreatic cancer in the ESPAC-1 Randomized Controlled Trial. Dig Surg 2005; 22:353–63.[CrossRef][Medline]
  27. Goldstein D, Carroll S, Apte M, Keogh G. Modern management of pancreatic carcinoma. Intern Med J 2004; 34:475–81.[CrossRef][Medline]
  28. Koeppler H, Duru M, Grundheber M, et al. Palliative treatment of advanced pancreatic carcinoma in community-based oncology group practices. J Support Oncol 2004; 2:159–63.[Medline]
  29. Prost P, Ychou M, Azria D. [Gemcitabine and pancreatic cancer]. Bull Cancer 2002; 89(Spec No):S91–5.[Medline]
  30. Cunningham D, Chau I, Stocken D, et al. Phase III randomised comparison of gemcitabine (GEM) versus gemcitabine plus capecitabine (GEM-CAP) in patients with advanced pancreatic cancer. Eur J Cancer 2005; 3:4;; (abstract PS11).
  31. Moore MJ, Goldstein D, Hamm J, et al. Erlotinib improves survival when added to gemcitabine in patients with advanced pancreatic cancer. A phase III trial of the National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG). J Clin Oncol 2005;ASCO Annual Meeting Proceedings. (abstract 77). Vol 23, No.16S, Part I of II (June 1 Supplement), 2005:1 41st Annual Meeting American Society of Clinical Oncology (ASCO) May 13–17, 2005 Orlando, Florida.
  32. Yamada H, Katoh H, Kondo S, Okushiba S, Morikawa T. Hepatectomy for metastases from non-colorectal and non-neuroendocrine tumor. Anticancer Res 2001; 21:4159–62.[Medline]
  33. Christophe M, Le Treut YP, Pol B, Brandone JM, Capobianco C, Bricot R. [Cancer of the pancreas. A plea for resection. 162 operated patients]. Presse Med 1992; 21:741–4.[Medline]
  34. Lillemoe KD, Cameron JL, Yeo CJ, et al. Pancreaticoduodenectomy. Does it have a role in the palliation of pancreatic cancer?. Ann Surg 1996; 223:718–25.[CrossRef][Medline]
  35. Beger HG, Thorab FC, Liu Z, Harada N, Rau BM. Pathogenesis and treatment of neoplastic diseases of the papilla of Vater: Kausch-Whipple procedure with lymph node dissection in cancer of the papilla of Vater. J Hepatobiliary Pancreat Surg 2004; 11:232–8.[Medline]
  36. Pedrazzoli S, Pasquali C, Sperti C. General aspects of surgical treatment of pancreatic cancer. Dig Surg 1999; 16:265–75.[CrossRef][Medline]
  37. Shimada K, Kosuge T, Yamamoto J, Yamasaki S, Sakamoto M. Successful outcome after resection of pancreatic cancer with a solitary hepatic metastasis. Hepatogastroenterology 2004; 51:603–5.[Medline]
  38. Sunada S, Miyata M, Tanaka Y, et al. Aggressive resection for advanced pancreatic carcinoma. Surg Today 1992; 22:74–7.[CrossRef][Medline]
  39. Burris HA III, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 1997; 15:2403–13.[Abstract/Free Full Text]
  40. Conroy T, Paillot B, Francois E, et al. Irinotecan plus oxaliplatin and leucovorin-modulated fluorouracil in advanced pancreatic cancer—a Groupe Tumeurs Digestives of the Federation Nationale des Centres de Lutte Contre le Cancer study. J Clin Oncol 2005; 23:1228–36.[Abstract/Free Full Text]
  41. Van Cutsem E, van de Velde H, Karasek P, et al. Phase III trial of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in advanced pancreatic cancer. J Clin Oncol 2004; 22:1430–8.[Abstract/Free Full Text]
  42. Cress RD, Yin D, Clarke L, Bold R, Holly EA. Survival among patients with adenocarcinoma of the pancreas: a population-based study (United States). Cancer Causes Control 2006; 17:403–9.[CrossRef][Medline]
  43. Carpelan-Holmstrom M, Nordling S, Pukkala E, et al. Does anyone survive pancreatic ductal adenocarcinoma? A nationwide study re-evaluating the data of the Finnish Cancer Registry. Gut 2005; 54:385–7.[Abstract/Free Full Text]
  44. Connor S, Bosonnet L, Ghaneh P, et al. Survival of patients with periampullary carcinoma is predicted by lymph node 8a but not by lymph node 16b1 status. Br J Surg 2004; 91:1592–9.[CrossRef][Medline]
  45. Farnell MB, Pearson RK, Sarr MG, et al. A prospective randomized trial comparing standard pancreatoduodenectomy with pancreatoduodenectomy with extended lymphadenectomy in resectable pancreatic head adenocarcinoma. Surgery 2005; 138:618–28.[CrossRef][Medline]
  46. Henne-Bruns D, Vogel I, Luttges J, Kloppel G, Kremer B. Ductal adenocarcinoma of the pancreas head: survival after regional versus extended lymphadenectomy. Hepatogastroenterology 1998; 45:855–66.[Medline]
  47. Nimura Y, Nagino M, Kato H, et al. Standard versus extended lymphadenectomy for pancreatic cancer: a multicenter, randomized controlled trial. Pancreatology 2004; 4:274.[CrossRef]
  48. Klempnauer J, Ridder GJ, Piso P, Pichlmayr R. [Is liver resection in metastases of exocrine pancreatic carcinoma justified?]. Chirurg 1996; 67:366–70.[Medline]
  49. Louvet C, Labianca R, Hammel P, et al. Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. J Clin Oncol 2005; 23:3509–16.[Abstract/Free Full Text]
  50. Ueno H, Okusaka T, Ikeda M, Takezako Y, Morizane C. An early phase II study of S-1 in patients with metastatic pancreatic cancer. Oncology 2005; 68:171–8.[CrossRef][Medline]




This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Shrikhande, S. V.
Right arrow Articles by Büchler, M. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shrikhande, S. V.
Right arrow Articles by Büchler, M. W.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS