Vikas Dudeja and Alan LivingstoneMiami， USA

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ls age just a number： pancreaticoduodenectomy in elderly patients？

Vikas Dudeja and Alan Livingstone
Miami， USA

Pancreatic cancer incidence is increasing worldwide.［1］While the developed countries have seen a greater increase in the age-standardized incidence rate of pancreatic cancer （29% from 1990-2013）， developing countries are also not spared （10% increase during the same time period）.［1］This change is believed to be due to not only aging and changing composition of the population， but also a true increase in the incidence. Like many other cancers， pancreatic and other periampullary malignancies disproportionately affect the elderly. Due to the changing landscape with an increasing incidence as well as a larger at risk elderly population， the medical community must be prepared to care for older patients with periampullary malignancy who may be candidates for pancreaticoduodenectomy. Given the magnitude of the operation and its potential ramifications， expertise is required to prevent unnecessary morbidity and mortality， and the medical community must ensure that good surgical candidates are not denied the potential benefit of curative surgery.

The Whipple operation has justifiably been recognized as a major procedure with significant morbidity. Until the 1980's， pancreaticoduodenectomy for periampullary malignancies was associated with very high mortality and morbidity， which when viewed in the context of poor oncologic outcomes， not surprisingly induced pessimism and led many to recommend only palliativecare for these unfortunate patients.［2］However， with improvement in preoperative preparation， surgical technique and perioperative care， the surgical mortality has decreased substantially. Today perioperative mortality of ＜2% is the norm when pancreaticoduodenectomy is performed by an experienced surgeon at a high volume center. With improved surgical outcomes， the indications for pancreatic resection have continued to expand and pancreaticoduodenectomy is now commonly offered to patients over 70 years of age. While the definition of elderly varies， data from major surgical centers in the developed world demonstrate that pancreatic resection in the elderly can be performed safely. Mortality rates in the elderly are typically less than 5% at high volume centers specializing in pancreatic surgery.［3］Elderly patients experience somewhat more postoperative complications，but in most surgical series this increase did not reach statistical significance.［3］

The other potential reason for nihilism towards pancreatic cancer is the fact that the outcome， even for those who undergo surgical resection， continues to be disheartening and has not improved substantially over the last 3 decades.［4］Most series suggest that patients with pancreatic adenocarcinoma who undergo a Whipple operation have only a 20% 5-year actuarial survival. Nonetheless，surgery continues to be standard of care for this disease as it is currently the only hope for cure. Patients not candidates for surgery who are treated with FOLFIRINOX， the best chemotherapy currently available， have a median overall survival of only 11 months with only a handful of patients making it to 2 years.［5］While there is selection bias at play in these statistics， there is a strong and clear association between having a Whipple operation and better outcomes. Intriguingly data suggest that elderly patients enjoy a similar oncologic advantage with resection when compared to their younger counterparts. In light of this， denying patients the potential benefits of resection because of age alone， without a detailed discussion of risk and benefits， expected outcome and quality of life issues， is not standard of care and is possibly unethical.

Most of the data on perioperative and oncologic outcomes following pancreaticoduodenectomy has originated from developed countries， and the extent to which the results are applicable to developing countries is not known. In the current issue， El Nakeeb et al［6］describe their experience with pancreaticoduodenectomy performed at a high volume tertiary referral center in Egypt from 1995-2015. This is one of the largest experiences of pancreaticoduodenectomy from this part of the world. The outcomes reported are excellent which suggests that high volume centers in developing nations can replicate the progress made in other parts of the world. The authors also demonstrated that while elderly patients experienced an increased incidence of delayed gastric emptying， the overall incidence of postoperative other complications and hospital mortality was not statistically different. Data like this is essential so that physicians are familiar with the best options for treating pancreatic cancer， and can thereby help patients make the most informed decisions regarding their care.

Is age just a number？ Aging is associated with an increased prevalence of comorbidities， worsening performance status， and increase in the difficulty to quantify variable of “frailty”. While frailty increases with age， patients with the same chronological age may have strikingly different biological ages. Thus， using some measure of frailty rather than using chronological age may be a better predictor of outcomes. Tegels et al［7］observed that in patients undergoing gastric cancer surgery， the Groningen Frailty Indicator as well as Short Nutritional Assessment Questionnaire were much stronger predictors of in-hospital mortality （odds ratio of 4 and 5， respectively）when compared to age （odds ratio of 1.11）. In the elderly population， standard outcome measures may not suffice and one has to consider and measure the probability that an individual may never return to his/her preoperative functional status. Seniors routinely consider quality to be more important than quantity of life.

El Nakeeb and his team［6］have provided further evidence that pancreaticoduodenectomy can be performed safely in the elderly with reasonable morbidity and mortality， and not just in highly developed countries. This complex operation needs to be performed by an experienced team at a high volume center. Surgery is currently the only chance for cure of pancreatic cancer， and physicians should not be nihilistic when it comes to recommending surgery to a chronologically older patient with a good performance status.

Contributors： DV and LA wrote the manuscript. LA is the guarantor.

Funding： None.

Ethical approval： Not needed.

Competing interest： No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

References

1 Global Burden of Disease Cancer Collaboration， Fitzmaurice C， Dicker D， Pain A， Hamavid H， Moradi-Lakeh M， et al. The global burden of cancer 2013. JAMA Oncol 2015；1：505-527.

2 Crile G Jr. The advantages of bypass operations over radical pancreatoduodenectomy in the treatment of pancreatic carcinoma. Surg Gynecol Obstet 1970；130：1049-1053.

3 Riall TS. What is the effect of age on pancreatic resection？ Adv Surg 2009；43：233-249.

4 Winter JM， Brennan MF， Tang LH， D'Angelica MI， Dematteo RP， Fong Y， et al. Survival after resection of pancreatic adenocarcinoma： results from a single institution over three decades. Ann Surg Oncol 2012；19：169-175.

5 Conroy T， Desseigne F， Ychou M， Bouché O， Guimbaud R， Bécouarn Y， et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011；364：1817-1825.

6 El Nakeeb A， Atef E， El Hanafy E， Salem A， Askar W， Ezzat H， et al. Outcomes of pancreaticoduodenectomy in elderly patients. Hepatobiliary Pancreat Dis Int 2016；15：419-427.

7 Tegels JJ， de Maat MF， Hulsewé KW， Hoofwijk AG， Stoot JH. Value of geriatric frailty and nutritional status assessment in predicting postoperative mortality in gastric cancer surgery. J Gastrointest Surg 2014；18：439-446.

Accepted after revision May 16， 2016

Author Affiliations： Division of Surgical Oncology， DeWitt Daughtry Family Department of Surgery， University of Miami Miller School of Medicine， Miami， FL， USA （Dudeja V and Livingstone A）

Alan Livingstone， MD， Professor of Surgery，Division of Surgical Oncology， University of Miami Miller School of Medicine， Jackson Memorial Hospital/Sylvester Comprehensive Cancer Center， 1120 NW 14th Street， CRB C232， Miami， FL 33136， USA （Email：alivings@med.miami.edu）
? 2016， Hepatobiliary Pancreat Dis Int. All rights reserved.

10.1016/S1499-3872（16）60108-X
Published online June 7， 2016.

May 9， 2016