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Margin Positive Pancreaticoduodenectomy Is Superior to Palliative Bypass in Locally Advanced Pancreatic Ductal Adenocarcinoma

  • 2009 SSAT Plenary Presentation
  • Published:
Journal of Gastrointestinal Surgery Aims and scope

Abstract

Background

Pancreatic ductal adenocarcinoma is an aggressive disease. Surgical resection with negative margins (R0) offers the only opportunity for cure. Patients who have advanced disease that limits the chance for R0 surgical resection may undergo margin positive (MP) pancreaticoduodenectomy (PD), palliative surgical bypass (PB), celiac plexus neurolysis alone (PX), or neoadjuvant chemoradiation therapy in anticipation of future resection.

Objective

The aim of this study was to determine if there is a difference in the perioperative outcomes and survival patterns between patients who undergo MP PD and those who undergo PB for locally advanced disease in the treatment of pancreatic ductal adenocarcinoma.

Methods

We reviewed our pancreatic surgery database (January 2005–December 2007) to identify all patients who underwent exploration with curative intent of pancreatic ductal adenocarcinoma of the head/neck/uncinate process of the pancreas. Four groups of patients were identified, R0 PD, MP PD, PB, and PX.

Results

We identified 126 patients who underwent PD, PB, or PX. Fifty-six patients underwent R0 PD, 37 patients underwent MP PD, 24 patients underwent a PB procedure, and nine patients underwent PX. In the PB group, 58% underwent gastrojejunostomy (GJ) plus hepaticojejunostomy (HJ), 38% underwent GJ alone, and 4% underwent HJ alone. Of these PB patients, 25% had locally advanced disease and 75% had metastatic disease. All nine patients in the PX group had metastatic disease. The mean age, gender distribution, and preoperative comorbidities were similar between the groups. For the MP PD group, the distribution of positive margins on permanent section was 57% retroperitoneal soft tissue, 19% with more than one positive margin, 11% pancreatic neck, and 8% bile duct. The perioperative complication rates for the respective groups were R0 36%, MP 49%, PB 33%, and PX 22%. The 30-day perioperative mortality rate for the entire cohort was 2%, with all three of these deaths being in the R0 group. The median follow-up for the entire cohort was 14.4 months. Median survival for the respective groups was R0 27.2 months, MP 15.6 months, PB 6.5 months, and PX 5.4 months.

Conclusions

Margin positive pancreaticoduodenectomy in highly selected patients can be performed safely, with low perioperative morbidity and mortality. Further investigation to determine the role of adjuvant treatment and longer-term follow-up are required to assess the durability of survival outcomes for patients undergoing MP PD resection.

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Author information

Authors and Affiliations

  1. Department of Surgery, Thomas Jefferson University, Jefferson Pancreas, Biliary and Related Cancer Center, Philadelphia, PA, USA

    Harish Lavu, Andres A. Mascaro, Dane R. Grenda, Patricia K. Sauter, Benjamin E. Leiby, Sean P. Croker, Adam C. Berger, Ernest L. Rosato, Eugene P. Kennedy & Charles J. Yeo

  2. Department of Pathology, Thomas Jefferson University, Jefferson Pancreas, Biliary and Related Cancer Center, Philadelphia, PA, USA

    Agnes Witkiewicz

  3. Department of Surgery, Thomas Jefferson University, 1025 Walnut Street, College Bldg., Suite 605, Philadelphia, PA, 19107, USA

    Harish Lavu

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  1. Harish Lavu
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Correspondence to Harish Lavu.

Additional information

Discussant

Dr. Attila Nakeeb (Indianapolis, IN): Clearly your group has again shown that achieving an RO resection margin is the most important factor in the management of pancreatic cancer. I have got a couple of questions regarding your philosophy and strategy in regards to these patients.

When you compare the palliative bypass group to the patients undergoing positive margin resection, almost 75% of your palliative bypass patients actually were bypassed in the setting of metastatic disease and not for locally advanced disease. I would like to get a feeling for your thoughts of whether surgical bypass and palliation are actually necessary in patients with metastatic disease. Do you employ any additional staging such as laparoscopy in patients with suspected metastatic disease, especially in patients with elevated CA 19–9 levels, because those have a much higher incidence of requiring palliative bypass.

Secondly, what is your approach to patients with borderline resectable tumors at Jefferson? Are those patients being taken to the operating room immediately with the plan for venous resection, or are they all going for neoadjuvant therapy? 

Finally, in those patients that are not able to have an R0 resection, if you compare your margin positive Whipples to the palliative bypass patients, is there any difference in the number of patients that actually receive adjuvant therapy postoperatively or in the time it takes to start therapy?

Closing Discussant

Dr. Harish Lavu (Philadelphia, PA): Your first question asked about whether or not we routinely perform diagnostic laparoscopy given the high percentage of patients with metastatic disease. The answer is that in the majority of patients, we do not. We rely heavily on the CAT scan to help us differentiate these patients, and what we have found is that the majority of unresectable patients ultimately require some sort of palliative bypass, whether it be to the biliary tree or the gastrointestinal tract. We generally believe palliative bypass to be superior to endoscopic management in terms of quality of life in those patients who undergo exploration, so we do not routinely perform laparoscopy.

Your second question was regarding patients with borderline resectable disease, and how we select patients for neoadjuvant treatment? Patients who have superior mesenteric vein or portal vein occlusion or who have a greater than 180° encasement of these vessels with significant stenosis of the vein, or patients who have superior mesenteric artery or celiac axis abutment of tumor. Those are the kinds of patients that we routinely send for neoadjuvant treatment.

Your third question on adjuvant treatment, unfortunately I cannot answer. Many of our patients do not receive their adjuvant treatment at our facility and so it is difficult for us to get a good handle on who was receiving treatment and who was not and when.

Discussant

Dr. L. William Traverso (Seattle, WA): I would like to congratulate the Thomas Jefferson group—with the plethora of great research coming out of Philadelphia on this disease. We look forward to many more contributions.

I am trying to think now not as a surgeon but as a medical oncologist. I note that the 13 months in survival time for the nonresected group outstrips that of the literature, which is about 9 months. You have already made progress there. In Seattle, it is 18 months for the nonresected group, higher than your margin positive Whipple group. Part of this may be experience to choose which chemotherapy will allow a response so it is no longer as much empiric but targeted therapy, somewhat.

I wonder if you might consider the following study—a patient totally managed endoscopically with stents, screened with prechemo laparoscopy (the latter will removed 28% of the patients as they will have positive peritoneal cytology), and then targeted therapy. Therefore, you have the perfect group to compare to the margin positive resected group. I expect in the next 5 years that we will observe 3- or 4-year survivors without any surgery, as we have seen in Seattle. Would you consider that study?

Closing Discussant

Dr. Harish Lavu (Philadelphia, PA): I think we would consider that. It is a very interesting point that you bring up. I would say that there are a number of studies now that are questioning the difference in outcomes between R0 resection and margin positive resections, specifically R1 resections, in terms of how it affects survival and to what time frame does it affect survival?

We know that surgical resection is superior to any adjuvant treatment that is commonly used today. So I think that if there are breakthroughs in adjuvant treatment in the future, there may develop a more aggressive philosophy toward taking patients for surgical resection.

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Lavu, H., Mascaro, A.A., Grenda, D.R. et al. Margin Positive Pancreaticoduodenectomy Is Superior to Palliative Bypass in Locally Advanced Pancreatic Ductal Adenocarcinoma. J Gastrointest Surg 13, 1937–1947 (2009). https://doi.org/10.1007/s11605-009-1000-x

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