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Morbidity and Mortality after Pancreaticoduodenectomy in Patients with Borderline Resectable Type C Clinical Classification

  • 2013 SSAT Plenary Presentation
  • Published:
Journal of Gastrointestinal Surgery Aims and scope

Abstract

Background

We previously described the clinical classification of patients with resectable pancreatic tumor anatomy but marginal performance status (PS) or reversible comorbidities as “borderline resectable type C” (BR-C). This study was designed to analyze the incidence and risk factors for post-pancreaticoduodenectomy (PD) morbidity/mortality in a multi-institutional cohort of BR-C patients.

Methods

Elective PDs were evaluated from the 2005-10 ACS-NSQIP database. BR-C was defined as age ≥ 80, poor PS, weight loss > 10 %, pulmonary disease, recent myocardial infarction/angina, stroke history, and/or preoperative sepsis. Variables associated with 30-day postoperative major complications (PMC) and mortality were analyzed.

Results

A total of 3,033/8,266 (36.7 %) patients were BR-C. BR-C patients were more likely to suffer PMC (31.3 vs. 26.2 %) and mortality (4.1 vs. 2.3 %). BR-C patients with PMC suffered 50 % higher mortality versus non-BR-C patients with PMC (11.5 vs. 7.7 %) (all p < 0.001). For BR-C patients, multivariate analysis identified the following risk factors for PMC or mortality: albumin < 3.5 g/dL, dyspnea, preoperative sepsis, age ≥ 80, poor PS, anesthesia score ≥ 4, and intraoperative transfusion ≥ 4 units.

Conclusions

Nationwide, one third of patients undergoing PD are medically borderline. These BR-C patients are at higher risk for and less able to be rescued from PMC. Surgeons should identify and optimize comorbidities and utilize prehabilitation to address functional deficits before elective PD.

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References

  1. Cameron JL, Riall TS, Coleman J, Belcher KA. One thousand consecutive pancreaticoduodenectomies. Ann Surg. Jul 2006;244(1):10–15.

    Google Scholar 

  2. Winter JM, Brennan MF, Tang LH, D'Angelica MI, Dematteo RP, Fong Y, Klimstra DS, Jarnagin WR, Allen PJ. Survival after resection of pancreatic adenocarcinoma: results from a single institution over three decades. Ann Surg Oncol. Jan 2012;19(1):169–175.

    Google Scholar 

  3. Ziegler KM, Nakeeb A, Pitt HA, Schmidt CM, Bishop SN, Moreno J, Matos JM, Zyromski NJ, House MG, Madura JA, Howard TJ, Lillemoe KD. Pancreatic surgery: evolution at a high-volume center. Surgery. Oct 2010;148(4):702–709; discussion 709–710.

    Google Scholar 

  4. Finks JF, Osborne NH, Birkmeyer JD. Trends in hospital volume and operative mortality for high-risk surgery. N Engl J Med. Jun 2 2011;364(22):2128–2137.

    Google Scholar 

  5. Ghaferi AA, Birkmeyer JD, Dimick JB. Hospital volume and failure to rescue with high-risk surgery. Med Care. Dec 2011;49(12):1076–1081.

    Google Scholar 

  6. Katz MH, Wang H, Fleming JB, Sun CC, Hwang RF, Wolff RA, Varadhachary G, Abbruzzese JL, Crane CH, Krishnan S, Vauthey JN, Abdalla EK, Lee JE, Pisters PW, Evans DB. Long-term survival after multidisciplinary management of resected pancreatic adenocarcinoma. Annals of surgical oncology. Apr 2009;16(4):836–847.

    Google Scholar 

  7. Greenblatt DY, Kelly KJ, Rajamanickam V, Wan Y, Hanson T, Rettammel R, Winslow ER, Cho CS, Weber SM. Preoperative factors predict perioperative morbidity and mortality after pancreaticoduodenectomy. Ann Surg Oncol. Aug 2011;18(8):2126–2135.

    Google Scholar 

  8. Vollmer CM, Jr., Sanchez N, Gondek S, McAuliffe J, Kent TS, Christein JD, Callery MP. A root-cause analysis of mortality following major pancreatectomy. J Gastrointest Surg. Jan 2012;16(1):89–102; discussion 102–103.

    Google Scholar 

  9. Katz MH, Pisters PW, Evans DB, Sun CC, Lee JE, Fleming JB, Vauthey JN, Abdalla EK, Crane CH, Wolff RA, Varadhachary GR, Hwang RF. Borderline resectable pancreatic cancer: the importance of this emerging stage of disease. J Am Coll Surg. May 2008;206(5):833–846; discussion 846–838.

    Google Scholar 

  10. Tzeng CW, Fleming JB, Lee JE, Xiao L, Pisters PW, Vauthey JN, Abdalla EK, Wolff RA, Varadhachary GR, Fogelman DR, Crane CH, Balachandran A, Katz MH. Defined clinical classifications are associated with outcome of patients with anatomically resectable pancreatic adenocarcinoma treated with neoadjuvant therapy. Ann Surg Oncol. Jun 2012;19(6):2045–2053.

    Google Scholar 

  11. Strasberg SM, Hall BL. Postoperative morbidity index: a quantitative measure of severity of postoperative complications. J Am Coll Surg. Nov 2011;213(5):616–626.

    Google Scholar 

  12. Pitt HA, Kilbane M, Strasberg SM, Pawlik TM, Dixon E, Zyromski NJ, Aloia TA, Henderson JM, Mulvihill SJ. ACS-NSQIP has the potential to create an HPB-NSQIP option. HPB (Oxford). Aug 2009;11(5):405–413.

  13. Al-Refaie WB, Parsons HM, Henderson WG, Jensen EH, Tuttle TM, Vickers SM, Rothenberger DA, Virnig BA. Major cancer surgery in the elderly: results from the American College of Surgeons National Surgical Quality Improvement Program. Ann Surg. Feb 2010;251(2):311–318.

    Google Scholar 

  14. Silber JH, Romano PS, Rosen AK, Wang Y, Even-Shoshan O, Volpp KG. Failure-to-rescue: comparing definitions to measure quality of care. Med Care. Oct 2007;45(10):918–925.

    Google Scholar 

  15. 2010 Census Briefs: Age and Sex Composition 2010. 2011; http://www.census.gov/prod/cen2010/briefs/c2010br-03.pdf. Accessed March 14, 2013.

  16. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. Jan-Feb 2012;62(1):10–29.

  17. Makary MA, Winter JM, Cameron JL, Campbell KA, Chang D, Cunningham SC, Riall TS, Yeo CJ. Pancreaticoduodenectomy in the very elderly. J Gastrointest Surg. Mar 2006;10(3):347–356.

    Google Scholar 

  18. Kassin MT, Owen RM, Perez SD, Leeds I, Cox JC, Schnier K, Sadiraj V, Sweeney JF. Risk factors for 30-day hospital readmission among general surgery patients. J Am Coll Surg. Sep 2012;215(3):322–330.

    Google Scholar 

  19. Lee MK, Dinorcia J, Reavey PL, Holden MM, Genkinger JM, Lee JA, Schrope BA, Chabot JA, Allendorf JD. Pancreaticoduodenectomy can be performed safely in patients aged 80 years and older. J Gastrointest Surg. Nov 2010;14(11):1838–1846.

    Google Scholar 

  20. Lightner AM, Glasgow RE, Jordan TH, Krassner AD, Way LW, Mulvihill SJ, Kirkwood KS. Pancreatic resection in the elderly. J Am Coll Surg. May 2004;198(5):697–706.

    Google Scholar 

  21. Eeson G, Chang N, McGahan CE, Khurshed F, Buczkowski AK, Scudamore CH, Warnock GL, Chung SW. Determination of factors predictive of outcome for patients undergoing a pancreaticoduodenectomy of pancreatic head ductal adenocarcinomas. HPB (Oxford). May 2012;14(5):310–316.

    Google Scholar 

  22. Aloia TA, Lee JE, Vauthey JN, Abdalla EK, Wolff RA, Varadhachary GR, Abbruzzese JL, Crane CH, Evans DB, Pisters PW. Delayed recovery after pancreaticoduodenectomy: a major factor impairing the delivery of adjuvant therapy? J Am Coll Surg. Mar 2007;204(3):347–355.

    Google Scholar 

  23. Relles DM, Richards NG, Bloom JP, Kennedy EP, Sauter PK, Leiby BE, Rosato EL, Yeo CJ, Berger AC. Serum blood urea nitrogen and serum albumin on the first postoperative day predict pancreatic fistula and major complications after pancreaticoduodenectomy. J Gastrointest Surg. Feb 2013;17(2):326–331.

    Google Scholar 

  24. Braga M. Perioperative immunonutrition and gut function. Curr Opin Clin Nutr Metab Care. Sep 2012;15(5):485–488.

    Google Scholar 

  25. Mauskopf JA, Candrilli SD, Chevrou-Severac H, Ochoa JB. Immunonutrition for patients undergoing elective surgery for gastrointestinal cancer: impact on hospital costs. World J Surg Oncol. 2012;10:136.

    Google Scholar 

  26. Braga M, Gianotti L, Radaelli G, Vignali A, Mari G, Gentilini O, Di Carlo V. Perioperative immunonutrition in patients undergoing cancer surgery: results of a randomized double-blind phase 3 trial. Arch Surg. Apr 1999;134(4):428–433.

    Google Scholar 

  27. Mayo NE, Feldman L, Scott S, Zavorsky G, Kim do J, Charlebois P, Stein B, Carli F. Impact of preoperative change in physical function on postoperative recovery: argument supporting prehabilitation for colorectal surgery. Surgery. Sep 2011;150(3):505–514.

    Google Scholar 

  28. Horowitz DP, Hsu CC, Wang J, Makary MA, Winter JM, Robinson R, Schulick RD, Cameron JL, Pawlik TM, Herman JM. Adjuvant chemoradiation therapy after pancreaticoduodenectomy in elderly patients with pancreatic adenocarcinoma. Int J Radiat Oncol Biol Phys. Aug 1 2011;80(5):1391–1397.

    Google Scholar 

  29. Bilimoria KY, Bentrem DJ, Lillemoe KD, Talamonti MS, Ko CY. Assessment of pancreatic cancer care in the United States based on formally developed quality indicators. J Natl Cancer Inst. Jun 16 2009;101(12):848–859.

    Google Scholar 

  30. Fong Y, Blumgart LH, Fortner JG, Brennan MF. Pancreatic or liver resection for malignancy is safe and effective for the elderly. Ann Surg. Oct 1995;222(4):426–434; discussion 434–427.

    Google Scholar 

  31. Ballarin R, Spaggiari M, Di Benedetto F, Montalti R, Masetti M, De Ruvo N, Romano A, Guerrini GP, De Blasiis MG, Gerunda GE. Do not deny pancreatic resection to elderly patients. J Gastrointest Surg. Feb 2009;13(2):341–348.

    Google Scholar 

  32. Kent TS, Sachs TE, Callery MP, Vollmer CM, Jr. The burden of infection for elective pancreatic resections. Surgery. Jan 2013;153(1):86–94.

    Google Scholar 

  33. Sun RC, Button AM, Smith BJ, Leblond RF, Howe JR, Mezhir JJ. A comprehensive assessment of transfusion in elective pancreatectomy: risk factors and complications. J Gastrointest Surg. Apr 2013;17(4):627–635.

    Google Scholar 

  34. Bernard AC, Davenport DL, Chang PK, Vaughan TB, Zwischenberger JB. Intraoperative transfusion of 1 U to 2 U packed red blood cells is associated with increased 30-day mortality, surgical-site infection, pneumonia, and sepsis in general surgery patients. J Am Coll Surg. May 2009;208(5):931–937, 937 e931-932; discussion 938–939.

    Google Scholar 

Download references

Sources of Funding

Supported by the Khalifa Bin Zayed Al Nahyan Foundation and the Various Donor Pancreatic Research Fund at The University of Texas MD Anderson Cancer Center.

Disclosures

TAA received reimbursement from Medtronic, Inc., for educational presentations unrelated to this study.

ACS-NSQIP Disclaimer for Participant Use File Research

The American College of Surgeons National Surgical Quality Improvement Program and the hospitals participating in the ACS-NSQIP are the source of the data used herein; they have not verified and are not responsible for the statistical validity of the data analysis or the conclusions derived by the authors.

Author information

Authors and Affiliations

  1. Department of Surgical Oncology, Unit 1484, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX, 77030, USA

    Ching-Wei D. Tzeng, Matthew H. G. Katz, Jason B. Fleming, Jeffrey E. Lee, Peter W. T. Pisters, Jean-Nicolas Vauthey & Thomas A. Aloia

  2. Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Holly M. Holmes

  3. Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Gauri R. Varadhachary, Robert A. Wolff & James L. Abbruzzese

Authors
  1. Ching-Wei D. Tzeng
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  2. Matthew H. G. Katz
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  3. Jason B. Fleming
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  4. Jeffrey E. Lee
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  5. Peter W. T. Pisters
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Corresponding author

Correspondence to Thomas A. Aloia.

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Discussion

Dr. Sean Mulvihill (Salt Lake City, Utah): Thank you, Dr. Tzeng. At first blush, this paper might not be interesting: sicker patients do worse than healthier patients. But I think there is depth in this analysis and congratulate the authors for bringing this information forward. They have examined over 8,200 Whipple patients in the NSQIP database with prospectively defined risk factors and outcomes measures and provide information on risk stratification that will become increasingly important as we attempt to judge the quality of our surgical outcomes. I have two questions and one observation for Dr. Aloia.

First, in the manuscript, the authors contend that nearly all the risk factors they chose in defining patients as borderline resectable because of comorbidities are potentially modifiable. However, in an era where we are embracing increasingly morbid neoadjuvant therapy, such as FOLFIRINOX protocols, I wonder how many patients will actually improve their functional status. Further, it appears that, at best, we might reduce serious complication rates from 31 to 26 %—not a dramatic improvement. So, my first question relates to the degree of benefit we might achieve with medical optimization in this group of patients.

Second, a clear trend in quality assessment is the use of administrative data, rather than carefully collected clinical outcome data such as we have with NSQIP. This is a trend fraught with potential for misuse and I ask the authors if they have compared their BR-C classification with the CMS severity of illness classification, Charlson morbidity scores, or University Healthsystem Consortium risk adjustment measures to identify areas of discordance.

Finally, an observation: The NSQIP has a serious limitation, in that we analyze only patients who have undergone procedures. A population perspective incorporating patients potentially treatable but rejected is necessary to assess decision-making around “appropriateness” of management—an area I predict will assume increasing importance in the near future.

My congratulations on an excellent contribution, we need more of this type of work.

Closing Discussant

Dr. Ching-Wei Tzeng: Dr. Mulvihill—thank you for your insightful comments.

Regarding your first question, our definition of borderline resectable type C (BR-C) does include patients who have medical comorbidities, physical conditioning issues, and nutritional deficits, which are potentially, but not consistently, modifiable. These patients are labeled as BR-C in their initial clinic visit so that early evaluation with internal medicine, geriatrics, physical therapy, and nutrition teams can be completed. If the patient has no anatomical or biological indications for neoadjuvant therapy, prehabilitation, and nutritional optimization can occur in just a few weeks, which is still oncologically acceptable. If there are indications for neoadjuvant sequencing, the regimen should be tailored to the performance status. While more toxic regimens are often chosen, those are reserved for our patients with ECOG 0-1 performance status, not for our patients in the BR-C group. Weaker patients would likely get a gemcitabine–cisplatin combination. Then, there is a treatment break of about 6 weeks after chemotherapy or chemoradiation for further prehabilitation and medical optimization before pancreatectomy. By taking the time to fix potentially reversible risk factors as we have identified, there is a chance to improve the overall mortality rate. As Dr. Mulvihill correctly points out, the absolute difference of major complication rates is only 5 % (from 31 to 26 %), but the failure to rescue rate is likely to improve as patients move out of the BR-C category during the preoperative period. This may improve overall mortality rates, which are almost double in the BR-C patients and would likely be higher if NSQIP extended capture of post-complication late deaths to 90 days after surgery. To answer the direct question you have posed, we have organized a clinical trial evaluating frailty and prehabilitation prior to pancreaticoduodenectomy. Hopefully, we can bring the data from this study to next year’s SSAT meeting.

Second, we originally conceptualized the BR-C classification system because it was very easy to stratify patients without the need to use any risk calculators. However, we would like to compare this subjective clinical classification system with the more objective risk scores used elsewhere in the surgical literature.

Finally, we totally agree that a limitation of “surgical” databases is that they do not fully reflect the entire potentially treatable cohort, by intent to treat. We agree that likely there were many patients with resectable pancreatic tumors who were already selected by surgeons not to receive pancreatectomy due to comorbidities. This practical reality only magnifies our findings that well over one third of those who did undergo pancreaticoduodenectomy could have been labeled as medically high-risk and may have benefited from preoperative optimization before their elective resections.

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Tzeng, CW.D., Katz, M.H.G., Fleming, J.B. et al. Morbidity and Mortality after Pancreaticoduodenectomy in Patients with Borderline Resectable Type C Clinical Classification. J Gastrointest Surg 18, 146–156 (2014). https://doi.org/10.1007/s11605-013-2371-6

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