Abstract
Introduction
Several studies have confirmed the safety of pancreatoduodenectomy with portal/mesenteric vein resection and reconstruction in select patients. The effect of vein invasion and extent of invasion on survival is less clear. The purpose of this study was to examine the association between tumor invasion of the portal/mesenteric vein and long-term survival.
Methods
A retrospective review of a prospectively maintained database of patients who underwent pancreatoduodenectomy for pancreatic adenocarcinoma at a single academic medical center (2000–2014) was performed. Survival was compared using the Kaplan–Meier method and log-rank test. P < 0.05 was considered statistically significant.
Results
After non-pancreatic periampullary adenocarcinomas and patients with non-segmental (lateral wall only) resection of portal/mesenteric vein were excluded, there were 567 eligible patients. Of these, segmental vein resection was performed in 90 (16 %) with end-to-end primary anastomosis (67) or interposition graft reconstruction (23). Patients with vein resection more likely received neoadjuvant systemic therapy (59 vs. 4 %, p < 0.0001). Histopathology of patients undergoing vein resection revealed a distribution of T stage toward larger tumors and higher rates of perineural invasion. Portal/mesenteric vein resection, however, was not associated with differences in hospital stay, postoperative complications, or operative mortality. Patients with or without vein resection had comparable overall survival rates at 1-, 3-, and 5-years. On final surgical histopathology, only 52 of 90 (58 %) vein resections had adenocarcinoma involvement of the venous wall. Of these, depth of invasion was at the level of the adventitia (9), media/intima (34), and full thickness/intraluminal (9). Venous wall invasion (52) did not significantly influence overall survival (14 vs. 21 months, p = 0.08) but was associated with significantly shorter median disease-free survival (11.3 vs. 15.8 months, p = 0.03), predominantly due to local recurrence. The extent of invasion (adventitia, media/intima, full thickness/intraluminal) did not impact overall survival or disease-free survival (14.4 vs. 15.5 vs. 7.4 months, p = 0.08 and 11.2 vs. 12.2 vs. 5 months, 0.59, respectively). Portal/mesenteric vein resection, histopathologic invasion, or the extent of invasion were not independent predictors of overall survival in Cox regression analysis.
Conclusion
Although Portal/mesenteric vein resection is associated with increased 90-day mortality, venous resection is not prognostic of overall survival. Although a subgroup analysis showed that a direct tumor invasion into the vein wall on final histopathology was associated with a higher rate of local recurrence but with no difference in overall survival (even when stratified according to extent of venous wall invasion), larger studies with an increased power will be needed to confirm these findings.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Explore related subjects
Discover the latest articles, news and stories from top researchers in related subjects.References
Howlader N, Noone AM, Krapcho M, Krapcho M, Garshell J, Neyman N et al. SEER Cancer Statistics Review, 1975–2010. National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2010/. Based on November 2012 SEER data submission posted to the SEER website, April 2013. Available from: http://seer.cancer.gov/statfacts/html/pancreas.html (last accessed April 2015).
Moore GE, Sako Y, Thomas LB. Radical pancreatoduodenectomy with resection and reanastomosis of the superior mesenteric vein. Surgery 1951;30:550–3.
Fortner JG. Regional resection of cancer of the pancreas: a new surgical approach. Surgery 1973;73:307–20.
Sobin LH, Wittekind C. International Union Against Cancer (UICC). TNM Classification of Malignant Tumors (6th ed). Wiley–Liss: New York, 2002.
National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Pancreatic Adenocarcinoma. Ed 2013. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp (last accessed May 2015).
Ishikawa O, Ohigashi H, Imaoka S, et al. Preoperative indications for extended pancreatectomy for locally advanced pancreas cancer involving the portal vein. Ann Surg. 1992;215:231–6.
Porembka, MR, Hawkins, WG, Linehan, DC et al. Radiologic and intraoperative detection of need for mesenteric vein resection in patients with adenocarcinoma of the head of the pancreas. HPB (Oxford) 2011;13(9): 633–42.
NCI dictionary of cancer terms. Available from http://www.cancer.gov/dictionary (Last accessed 02/10/2014).
Bockhorn M, Uzunoglu FG, Adham M et al. Borderline resectable pancreatic cancer: A consensus statement by the International Study Group of Pancreatic Surgery (ISGPS). Surgery 2014;155:977–88.
Exocrine and endocrine pancreas. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 241–9.
Leach SD, Lee JE, Charnsangavej C, et al. Survival following pancreaticoduodenectomy with resection of the superior mesenteric-portal vein confluence for adenocarcinoma of the pancreatic head. Br J Surg. 1998;85:611–7.
Siriwardana HP, Siriwardena AK. Systematic review of outcome of synchronous portal-superior mesenteric vein resection during pancreatectomy for cancer. Br J Surg. 2006;93:662–73.
Zhou Y, Zhang Z, Liu Y, Li B, Xu D. Pancreatectomy combined with superior mesenteric vein-portal vein resection for pancreatic cancer: a meta-analysis. World J Surg 2012; 36:884–91.
Evans DB, Farnell MB, Lillemoe KD, Vollmer C Jr, Strasberg SM, Schulick RD. Surgical treatment of resectable and borderline resectable pancreas cancer: expert consensus statement. Ann Surg Oncol 2009;16:1736–44.
Kelly KJ, Winslow E, Kooby D, Lad NL, Parikh AA, Scoggins CR, et al. Vein involvement during pancreaticoduodenectomy: is there a need for redefinition of “borderline resectable disease”? J Gastrointest Surg 2013;17:1209–17.
Yekebas EF, Bogoevski D, Cataldegirmen G, et al. En bloc vascular resection for locally advanced pancreatic malignancies infiltrating major blood vessels: perioperative outcome and long-term survival in 136 patients. Ann Surg 2008;247:300–9.
Shimada, K., Sano, T., Sakamoto, Y., and Kosuge, T., Clinical implications of combined portal vein resection as a palliative procedure in patients undergoing pancreaticoduodenectomy for pancreatic head carcinoma. Ann Surg Oncol 2006; 13(12): 1569–78.
Tseng JF, Raut CP, Lee JE, et al. Pancreaticoduodenectomy with vascular resection: margin status and survival duration. J Gastrointest Surg. 2004;8(8):935–49; discussion 949–50.
Wiersema MJ. Accuracy of endoscopic ultrasound in diagnosing and staging pancreatic carcinoma. Pancreatology. 2001;1:625–32.
Stein M, Schneider PD, Ho HS, Eckert R, Urayama S, Bold RJ. Percutaneous transhepatic portography with intravascular ultrasonography for evaluation of venous involvement of hepatobiliary and pancreatic tumors. J Vasc Interv Radiol. 2002;13:805–14.
Durup Scheel-Hincke J, Mortensen MB, Qvist N, Hovendal CP. TNM staging and assessment of resectability of pancreatic cancer by laparoscopic ultrasonography. Surg Endosc. 1999;13:967–71.
Kaneko T, Nakao A, Takagi H. Intraportal endovascular ultrasonography for pancreatic cancer. Semin Surg Oncol. 1998;15:47–51.
Hwang JW, Kim SC, Song KB et al. Significance of radiologic location and extent of portal venous involvement on prognosis after resection for pancreatic adenocarcinoma. Pancreas 2015 ;44 :665–71.
Delpero JR, Boher JM, Sauvanet A et al. Pancreatic adenocarcinoma with venous involvement: Is upfront synchronous portal-superior mesenteric vein resection still justified? A survey of the Association Francaise de Chirurgie. Ann Surg Oncol 2015 ;22 :1874–83.
Kaneoka Y, Yamaguchi A and Masatoshi I. Portal or superior mesenteric vein resection for pancreatic head adenocarcinima: prognostic value of the length of venous resection. Surgery 2009 ;145 :417–25.
Fukuda S, Oussoultzoglou E, Bachellier P, et al. Significance of the depth of portal vein wall invasion after curative resection for pancreatic adenocarcinoma. Arch Surg. 2007;142:172–9.
Nakao A, Kanzaki A, Fujii T et al. Correlation between radiographic classification and pathological grade of portal vein wall invasion in pancreatic head cancer. Ann Surg 2012;255:103–8.
Boggi U, Del Chiaro M, Croce C et al. Prognostic implications of tumor invasion or adhesion to peripancreatic vessels in resected pancreatic cancer. Surgery 2009;146:869–81.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Data were compiled and reported in strict compliance with patient confidentiality guidelines as defined by the Indiana University Institutional Review Board.
Conflict of Interest
The authors declare that they have no competing of interests.
Additional information
Primary Discussant
Ugo Boggi, MD, FEBS (Pisa, Italy)
Provided that resection and reconstruction of the portal/superior mesenteric vein during pancreatoduodenectomy is feasible and is associated with acceptable oncologic outcome, the next step is to gain further insights into this complex issue. This study presents important and compelling data in this perspective, and underlines the importance of detailed pathological analysis to further define indications and contraindications to this major operation.
The authors concluded, based on similar operative risk and survival than patients undergoing standard surgery, that portal/superior mesenteric vein should be resected if thought to be infiltrated. Histopathological invasion impacted tumor recurrence, but not overall survival, while depth of invasion did not impact long-term outcomes making resection an option in all patients when vein reconstruction is possible. The authors also recommended systemic neoadjuvant and adjuvant therapies.
Here are my questions.
1. You classified depth of tumor invasion into three levels: adventitia, media/intima, and lumen. Our group identified a negative prognostic significance of tumor invasion extending into the tunica intima as compared with more superficial involvement or no histologically documented infiltration. Can you comment on this?
2. I noted that three patients were staged T4 in the group with vein resection and one patient in the group without vein resection. T4 means arterial invasion. Did you perform also arterial resection in four patients? Was prognosis of these patients different from the rest of the cohort?
3. Do you have information on number of examined lymph nodes, number of positive lymph nodes, lymph node ratio, and metastatic para-aortic nodes?
Closing Discussant
Dr. Roch
1. Dr. Boggi, thank you for taking the time to discuss our paper. We agree with the findings from your group. Our study found that deeper involvement, especially when it reached the lumen, was associated with poorer prognosis, although it did not reach statistical significance (median disease-free survival: 11.3 vs. 12.2 vs. 5 months, p = 0.59; median overall survival: adventitia 14.4 vs. media/intima 15.5 vs. lumen 7.4 months, p = 0.50). Similarly to your series, we found that pathological invasion was associated with a significantly shorter median disease-free survival (11.3 vs. 15.8 months, p = 0.03) and a shorter median overall survival, although it failed short to reach statistical significance (14.4 vs. 21 months, p = 0.08). These findings have also been described by Nakao et al. published in Annals of Surgery in 2012. In this Japanese series, patients with histological invasion had a shorter overall survival than patients without histological invasion, but, similarly to our study, no statistical difference in terms of survival was found between the three layers of involvement.
Dr. Boggi, in your study, you separate media and intima, whereas in the present study we decided to lump them together. Although 90 patients with portal vein resection during pancreatoduodenectomy for pancreatic head adenocarcinoma represent one of the biggest series on this important topic, only 52 had true pathological invasion. Analyzing each wall layer separately would have led to a very small number of patients in each subcategory and the study would have lacked power.
2. Those four patients with T4 tumors had resection of the hepatic artery. No patient had resection of the superior mesenteric artery, as it is still considered a contra-indication to surgical resection and thus not performed at our institution. Those four patients underwent hepatic artery resection for tumor adherent to the artery, with the goal to extirpate the tumor. Arterial invasion was only noted on final pathology of the surgical specimen. The prognosis of those four patients was indeed poorer than most patients (one patient died 9 days after surgery from postoperative complications; for the three remaining patients, overall survival was 8.2, 11.3, and 11.7 months). However, those T4 tumors harbored many characteristics usually associated with poor prognosis (3/4 N1, 4/4 perineural invasion, 3/4 poorly differentiated, 1/4 moderately differentiated, and 2/4 positive margins). As we did not perform a multivariate analysis on those four patients, the influence of the arterial resection/invasion alone on overall survival is unknown.
3. Para-aortic lymph nodes are sampled at the beginning of the surgical procedure if they look suspicious for infiltration. If frozen section on those lymph nodes is positive for invasion, a surgical resection with curative intent is not performed as positive para-aortic lymph nodes are considered distant metastases, and thus a contra-indication to resection. Information on number of harvested lymph nodes, number of positive lymph nodes (and thus lymph node ratio) was prospectively collected in the database, but not retrospectively analyzed for the purpose of this study.
Alexandra M. Roch and Michael G. House contributed equally to this work.
Rights and permissions
About this article
Cite this article
Roch, A.M., House, M.G., Cioffi, J. et al. Significance of Portal Vein Invasion and Extent of Invasion in Patients Undergoing Pancreatoduodenectomy for Pancreatic Adenocarcinoma. J Gastrointest Surg 20, 479–487 (2016). https://doi.org/10.1007/s11605-015-3005-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11605-015-3005-y