Outcomes of pancreaticoduodenectomy in elderly patients

Ayman El Nakeeb， Ehab Atef， Ehab El Hanafy， Ali Salem， Waleed Askar，Helmy Ezzat， Ahmed Shehta and Mohamed Abdel WahabMansoura， Egypt

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Outcomes of pancreaticoduodenectomy in elderly patients

Ayman El Nakeeb， Ehab Atef， Ehab El Hanafy， Ali Salem， Waleed Askar，Helmy Ezzat， Ahmed Shehta and Mohamed Abdel Wahab
Mansoura， Egypt

BACKGROUND： Although the mortality and morbidity of pancreaticoduodenectomy （PD） have improved significantly over the past years， the concerns for elderly patients undergoing PD are still present. Furthermore， the frequency of PD is increasing because of the increasing proportion of elderly patients and the increasing incidence of periampullary tumors. This study aimed to analyze the outcomes of PD in elderly patients.

METHODS： We studied all patients who had undergone PD in our center between January 1995 and February 2015. The patients were divided into three groups based on age： group I （patients aged ＜60 years）， group II （those aged 60 to 69 years）and group III （those aged ≥70 years）. The primary outcome was the rate of total postoperative complications. Secondary endpoint included total operative time， hospital mortality，length of postoperative hospital stay， delayed gastric emptying，re-exploration， and survival rate.

RESULTS： A total of 828 patients who had undergone PD for resection of periampullary tumor were included in this study. There were 579 （69.9%） patients in group I， 201 （24.3%） in group II， and 48 （5.8%） in group III. The overall incidence of complications was higher in elderly patients （25.9% in group I， 36.8% in group II， and 37.5% in group III； P=0.006）. There were more patients complicated with delayed gastric emptying in group II compared with the other two groups. There was no significant difference in the incidence of postoperative pancreatic fistula， biliary leakage， pancreatitis， pulmonary complications and hospital mortality.

CONCLUSIONS： PD can be performed safely in selected elderly patients. Advanced age alone should not be a contraindication for PD. The outcome of elderly patients who have undergone PD is similar to that of younger patients， and the increased rate of complications is due to the presence of associated comorbidities.

（Hepatobiliary Pancreat Dis Int 2016；15：419-427）

pancreaticoduodenectomy；

elderly；

pancreatic fistula；

delayed gastric emptying

Introduction

Following the increase of life expectancy， the patients in general surgical department are getting older，about 60% of them are 65 years or older.［1］It is clear that the old age is one of the risk factors for the development of hepatobiliary and pancreatic tumors； the annual incidence of pancreatic tumors is 50 folds higher in the elderly than that in the young population，［2， 3］which leads to a dramatic increase in the number of elderly patients undergoing pancreaticoduodenectomy （PD）.［3， 4］PD remains the main line of treatment of periampullary tumors. Although PD is a major and complex operation which involves extensive resection and different reconstruction procedures， the mortality rate has dropped to less than 5% in many published series whereas the rate of postoperative complications remains high from 40% to 50%.［5-7］Recently， many studies［1-4］expanded the selection criteria for PD to elderly patients. The significant improvement in the outcome of PD has encouraged surgeons to approach periampullary tumors as aggressively in elderly as in younger patients. The PD selection in elderly patients depends on their health status such as cardiopulmonary function and surgeon's skills. Studies on the outcomes of PD for elderly patients are almost all from single high volume centers in theUnited State.［1-4， 7］It is difficult to decide whether PD is indicated for an older patient because of the existed comorbidity which resulted in postoperative complications and mortality. The benefit of PD for elderly patients is still debatable. Some studies reported the risk of morbidity and mortality of surgery in the elderly.［4， 8-10］However，others found that it almost carries no or minor risk compared to control patients.［1-3］The present study was to analyze the outcomes of PD in elderly patients in our center. lase level being 3 times greater than the normal amylase level. POPF was graded into A， B， and C according to the clinical course.［15］Delayed gastric emptying was defined as output from a nasogastric tube of greater than 500 mL per day that persisted beyond postoperative day 10， the failure to maintain oral intake by postoperative day 14，or reinsertion of a nasogastric tube.［15］Biliary leak was defined as the presence of bile in the drainage fluid that persisted to postoperative day 4.［15］

Methods

Patients

We analyzed all of the patients who underwent PD between January 1995 and February 2015 in Gastrointestinal Surgical Center， Mansoura University， Egypt. The indications for PD were periampullary tumors either benign or malignant， including ampullary tumors， pancreatic head cancers， lower end common bile duct tumors and duodenal tumors. We divided the patients into three groups based on age： group I （younger group， patients aged ＜60）， group II （aged 60 to 69 years） and group III （aged ≥70 years）. The institutional review board of the Mansoura Faculty of Medicine approved this study.

Patient data were collected from a prospectively maintained database since 2000 and from the archieve files between 1995 and 1999. The collected data included preoperative data， operative details， and postoperative complications and mortality. Only patients whose general conditions fulfilled the American Society of Anesthsiologists Physical Status Score Class I or II were considered as candidates of PD. Preoperative assessments such as cardiac and pulmonary functions were carried out. Preoperative details and postoperative data in our center have been described in our previous publications.［5， 11-13］

Statistical analysis

The data were analyzed using SPSS software， version 20 （Chicago， IL）. Descriptive data were expressed as mean±SD and compared by using the one-way ANOVA or expressed as median （range） and compared using the Kruskal-Wallis test depending on whether they were normally distributed or not. Categorical variables were expressed as percentages and compared using the Chisquare test. The overall survival times were calculated using the Kaplan-Meier method and compared using the log-rank test. Multivariate analysis was performed using the Cox regression model to identify the predictors of postoperative morbidities. A P value ＜0.05 was considered statistically significant.

Assessments

The primary parameter was the rate of total postoperative complications. We adopted the grading system of postoperative complications proposed by Clavien and Dindo classifications.［14］The secondary parameters included total operative time， hospital mortality， length of postoperative stay， time to resume oral intake， postoperative pancreatic fistula （POPF）， delayed gastric emptying，biliary leakage， bleeding pancreaticogastrostomy， bleeding gastrojejunostomy， internal hemorrhage， pulmonary complications， re-exploration， and survival rate.

POPF was defined by the International Study Group of Pancreatic Fistula （ISGPF） as any fluid volume of drained on or after postoperative day 3 with serum amy-

Results

Demographic data

In the 828 patients with periampullary tumors treated with PD， 579 （69.9%） were divided into group I， 201 （24.3%） group II and 48 （5.8%） group III， respectively. In the past 20 years， the number of elderly patients who underwent PD increased annually. About 4.5% （15/336）of the patients underwent the operation between 1995 and 2004； this number was markedly increased between 2005 and 2015 （6.7%， 33/492）. The median age of the patients was 56 years. The median age was 50 years in group I， 63 years in group II， and 71.5 years in group III. The three groups had similar gender distribution. Demographic and preoperative data of the patients are shown in Table 1.

Our center received 3782 patients with malignant obstructive jaundice over 20 years （Fig.）. Among them，2510 （66.4%） were pancreatic head cancer. Only 1404 out of 2510 （55.9%） patients with pancreatic head cancer were explored and 461/1404 （32.8%） were resectable. The overall resectable rate of pancreatic head cancer was 18.4% （461/2510）. This rate in patients below 60 years was 29.5% （327/1110）， between 60-69 years was 14.1% （110/779）， and over 70 years was 3.9% （24/621）.

The incidences of diabetes， hypertension， coronaryartery disease， and chronic obstructive pulmonary diseases were significantly higher in groups II and III than in group I （Table 1）.

Table 1. Demographic data

Fig. Patients with malignant obstructive jaundice over 20 years.

Operative and postoperative data

There was no difference in liver status， tumor size， pancreatic duct diameter， pancreatic texture， and blood loss among the three groups. The diameter of the common bile duct was significantly dilated in elderly patients （P=0.0001）. The total operative time was longer in group I than in group II （Table 2）.

The overall incidence of postoperative complications and their severity were significantly higher in elderly patients （25.9% in group I， 36.8% in group II， and 37.5% in group III； P=0.006）. There was no significant difference in the incidence of POPF and its severity， biliary leakage， pancreatitis， and pulmonary complications among the three groups. Delayed gastric emptying was more frequent in group II than in the other two groups. No significant differences were observed between the groups in the median length of hospital stay， the median day starting oral intake， and the duration of drainage. The serum albumin level decreased significantly on postoperative day 5 in elderly patients. The 1-， 2-， 3-year overall survival rates of the patients were 60%， 37%， and 22%，respectively with a median survival of 28 months. No significant difference was found in the median survival time and the 1-， 2-， 3-year overall survival rates among the three groups （Table 3）.

The risk factors of postoperative complications were analyzed by multivariate analysis. Pancreatic duct diameter ≤3 mm， age， preoperative ERCP， and BMI ≤25 kg/m2were found to be independent risk factors for the development of postoperative complications （Table 4）.

Table 2. Operative data

Pathology

The patients in the three groups had a higher incidence of malignant disease. Solid pseudopapillary tumor，neuroendocrinal tumor， and lymphoma are more common in patients aged below 60 years and rarely presented in older patients. There was no significant difference in different subtypes of periampullary tumors among the three groups. There was also no significant difference in the number of dissected lymph nodes， the number of infiltrated lymph nodes， lymph nodes ratio， pancreatic safety margin， perivascular infiltration， and perineural invasion （Table 5）.

Discussion

The incidence of periampullary tumor and related mortality has been increasing worldwide.［1-5］This leads to a dramatic increase in the number of elderly patients undergoing PD.［3， 4］PD is a complex and aggressive procedure with considerable complications. Despite the improvement of surgical techniques， pharmacological management， and precise patient selection for PD， the rate of postoperative complications is still around 40%.［4-8］

Age categories vary between countries， reflecting the social class differences or functional ability related to the workforce， not the political and economic situation. The definition of the elderly is usually linked to the retirement age.［16］Egypt has accepted the chronological age of 60 years as a definition of the elderly because the age of retirement in Egypt is 60 years which is associated with physical， psychological， and social changes.［17， 18］In Egypt，the average age of the population is increasing， with a life expectancy of 65.5 years for males in 1996 to 69.2 years in 2006. The average age of women is higher than that of men （69.2 and 73.6 years， respectively）.［17， 18］The life expectancy may influence the decision-making on PD. In the developed countries， the chronological age of 65 years has been defined as elderly.［16］Hence the median age of patients at operation in many countries appears to be higher than that in Egypt.［16-18］Aging increases vulnerability to age-associated diseases as atherosclerosis，cardiovascular diseases， pulmonary dysfunctions， cancer，psychological diseases， diabetes， hypertension， arthritis，anemia， nutritional disorder， and hypoalbuminemia，which increase the risk of surgical procedures and postoperative morbidity and mortality.［9， 10， 16-18］In the literature， there are various definitions of elderly. In the pres-ent study the elderly were divided into two groups： 60-69 years group and ≥70 years group and we compared the two elderly groups with younger patients of less than 60 years old.

Table 3. Postoperative data

POD： postoperative day； POPF： postoperative pancreatic fistula； SIRS： systemic inflammatory response syndrome.

The management of elderly patients with periampullary tumors remains challenging because of concerns regarding comorbidity， functional and nutritional status，mental status， social support and expected survival time after the operation.［19-26］The annual incidence of pancreatic tumors increases with advancement of age.［2， 3］Our study， showed that the number of patients of 70 years old undergoing PD increased annually. The percentage of patients aged more than 70 years who underwent PD increased from 4.5% （1995-2004） to 6.7% （2005-2015）.

The exploration rate of tumors decreased with aging because of the associated comorbidity which loweredthe resectable rate in the elderly. In fact， in patients selected for PD， those over 70 who had pancreatic head cancer had a resectable rate of 30.8% （24/78）， nearly the same as 33.2% （327/986） in younger patients below 60 years old （Fig.）.

Table 4. Multivariate analysis of risk factors of postoperative complication

Table 5. Postoperative pathology

Several studies［19-21］investigated the safety of PD for elderly patients and demonstrated that PD is effective；but once complications developed， the surgical outcomes may be fatal. Many studies［20-24］found that the rate of postoperative complications was comparable in elderly and younger patients if the incidence of preoperative comorbidity was the same. In this study， the overall incidence of postoperative complications and its severity were significantly higher in elderly patients. Complications were seen more frequent in these elderly patients.

Elderly patients are likely to be complicated with anemia and hypoalbuminamia which may attribute to mortality and morbidity.［25， 26］Anemia and hypoalbuminamia can be managed easily before surgery. In ourstudy， the hemoglobin and albumin levels were the same among the groups. But the recovery of serum albumin was delayed in the elderly. Hence， nutritional support for elderly patients after PD is needed to improve hypoalbuminamia.

Table 6. Outcomes of PD in the elderly from the literature

Studies［4， 7， 22-30］confirmed the high incidence of operative risks of PD in elderly patients. In our study， there was no significant difference in wound infection. Recent studies［27， 30-35］have shown the delayed recovery in elderly patients， with decreased the chance of adjuvant chemotherapy and high readmission rates after PD because of nutritional disorder， comorbidity or dehydration.

The mortality rate of elderly patients after PD can decrease to less than 3%.［2-6］Lee et al［30］demonstrated a decreased overall survival rate after PD for periampullary tumor. PD for pancreatic head cancer could not offer long-term survival in elderly patients as well as in young patients， but in patients with non pancreatic cancer it could achieve a long-term survival rate with a median survival of 82 months.［26］Hardacre et al［36］reported that the median survival for all patients aged above 80 years was 14.4 months. The outcomes of PD in elderly patients from the literature are summarized in Table 6.

With improved surgical techniques， instruments， and perioperative care， PD could be done safely in elderly patients with accepted postoperative complications. Ad-vanced age alone should not be a contraindication for PD， although nutritional supports are required after PD for elderly patients.［19， 23， 30， 36-42］The life expectancy may influence the decision-making for operation.

The limitations of this study are of retrospective nature； the number of patients above 80 years is relatively small （5， 0.6%）； the third limitation is the inability to calculate frailty score of the patients.

In conclusion， PD can be performed safely in selected elderly patients. Advanced age alone should not be a contraindication for PD. Nutritional support for elderly patients after PD should be recommended. Elderly patients are at risk of postoperative complications and mortality after PD but with an acceptable rate. The risk factors of development of postoperative complications are age， pancreatic duct diameter ≤3 mm， preoperative ERCP， and BMI ≤25 kg/m2. Careful selection of patients is the cornerstone to improve the outcome of PD in the elderly. An aggressive approach to pancreatic cancer， even in the elderly， can be justified in high volume centers in order to optimize resectability， and minimize morbidity and mortality.

Contributors： ENA proposed the study. ENA and AE wrote the first draft. ENA collected and analyzed the data. All authors contributed to the design and interpretation of the study and to further drafts. ENA is the guarantor.

Funding： None.

Ethical approval： This study was approved by the Institutional Review Board of Mansoura University （Egypt）.

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.

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Accepted after revision March 25， 2016

Author Affiliations： Gastroenterology Surgical Center， Mansoura University， Mansoura 35516， Egypt （El Nakeeb A， Atef E， El Hanafy E， Salem A，Askar W， Ezzat H， Shehta A and Abdel Wahab M）

Ayman El Nakeeb， MD， Associate Professor of General Surgery， Gastroenterology Surgical Center， Mansoura University，Mansoura 35516， Egypt （Tel： +20-10-6752021； Email： elnakeebayman@ yahoo.com）
? 2016， Hepatobiliary Pancreat Dis Int. All rights reserved.

10.1016/S1499-3872（16）60105-4
Published online May 23， 2016.

October 2， 2015