Pancreatic Surgery in the Aged Population: Technical and Molecular Insights

Abstract

Pancreatic resection is the only potentially curable treatment for pancreatic malignancies. Most of these malignancies occur in the aged population. In the past, these procedures were associated with significant morbidity and mortality. We herein reviewed recent advances in the knowledge of the physiological and immunological aspects of the aging process and improvements in the surgical techniques that have changed this scenario. We conclude that with appropriate selection, aged patients will outcomes similar to those of young patients, even after major pancreatic surgery.

Keywords: Pancreas; Cancer; Elderly; Surgery

Introduction

Pancreatic resection is currently the only curative treatment for pancreatic and biliary malignancies. Most of these malignancies occur mainly in aged patients [1]. In the past, pancreatic resection in the aged population was associated with increased morbidity and mortality rates of around 30% [2-4]. Indeed, aged patients have increased susceptibility to infection after surgical procedures [5].

Some recent reports, however, have shown that appropriate patient selection, establishment of good preoperative nutritional conditions, and appropriate management of the immunological and physiological changes that occur in the aged may reduce the morbidity and mortality associated with pancreatic resection [1], several other surgical procedures [6-9], and systemic inflammation in this population [10].

Aging and Systemic Inflammation

Aging is reportedly associated with a low-grade inflammatory state called inflammaging, which is characterized by higher production of proinflammatory cytokines than in younger patients [11].

Some studies have shown delayed increases in cytokine concentrations in aged patients after surgery [11]. We have also observed a delayed inflammatory response in aged patients who have undergone surgical procedures.

It is of paramount importance to consider that systemic inflammation is characterized by organ-specific alterations that may contribute to the increased morbidity in the aged population. In fact, we recently demonstrated that in a rodent model of acute pancreatitis, intestinal damage was much more severe in aged animals and was associated with increased bacterial translocation [12].

Such organ-specific alterations were further demonstrated in an experimental model of lung injury under conditions of systemic inflammation, in which the alterations were more severe in aged animals. The aged animals exhibited higher inducible nitric oxide synthase expression and lower extracellular superoxide dismutase expression than did young animals [13].

This low-grade inflammatory state is further documented by observation of monocyte activation and hypercytokinemia in aged patients following surgical interventions [14]. It has also been shown that mitogen-stimulated peripheral mononuclear cells in aged patients produce significantly higher levels of tumor necrosis factor (TNF)-a, interleukin (IL)-6 and IL-1-ß than do those in young patients [15].

Molecular Mechanisms of Age-Related Low- Grade Inflammatory State

Although several studies have been performed, the molecular mechanisms involved in inflammaging remain poorly understood. Involvement of the poly(ADP-ribose) polymerase-1 gene in inflammation and the aging process [16], the higher splenic tissue concentration of a-2A adrenergic receptors and phosphodiesterases, and the increased CD14 and toll-like receptor-4 expression in aged animals with sepsis are also associated with this increased inflammatory state in aged humans [17]. In a previous study of gene expression in aged patients with sepsis, we found disturbances in genes related to oxidative phosphorylation and mitochondrial function in peripheral neutrophils and considered that these disturbances may interfere with the neutrophils’ antimicrobial function [18].

Evaluation of the Aged Patient

When evaluating whether an aged patient is a candidate for pancreatic resection, we must use various biomarkers that will help to determine if the patient is fit for the procedure. One of these biomarkers is the patient’s walking speed. A previous study demonstrated an association between slower walking speeds and higher mortality rates [19]. Body composition (high body mass index) is also associated with age-related diseases, and a higher risk of mortality is associated with increased body fat and an increased waist circumference (>94cm for men and >77cm for women [20]. Certain inflammatory biomarkers of the aging process, such as IL-6, IL-1-ß, TNF-a, and C-reactive protein, are associated with various biophysical markers such as grip strength and gait speed, and may be used to evaluate the functional status of an aged patient [21]. Novel biomarkers are currently being evaluated and may be used in the future to better evaluate aged patients.

Pancreatic Resection in Aged Patients

Several recent studies of the feasibility of major pancreatic resection in the aged population have demonstrated that with appropriate perioperative management, aged patients may have outcomes similar to those of younger patients. Several reports have also shown that even more aggressive pancreatic resection in aged patients with vascular involvement is feasible without increased mortality [22].

A recent study unexpectedly found that aged patients undergoing very aggressive procedures such as modified Apple by pancreatic resection may have an even better prognosis than younger patients [23].

We studied 214 patients who had undergone pancreaticoduodenectomy in our center. The patients were divided into two groups based on age: Group I (patients aged <70 years) and Group II (those aged =70 years). The overall incidence of complications in Group II was 42.85%, while that in Group I was 28.5% (Table I). The overall incidence of complications among all 214 patients who underwent pancreaticoduodenectomy was 31.77%. All patients survived to the surgical procedure.

  

    
Age
    
Number of patients
    
number of    complications (%)
  
  

    
70 yrs
    
49
    
21 (42.85)
  
  

    
< 70 yrs
    
165
    
47 (28.5)
  
  

    
p    = 0.0577 (chi-square test).
      
 
  

Table 1: Pancreaticoduodenectomy in patients <70 and =70 years (personal
data).

    

    

    Figure 1:  Schematic model of the inflammatory response in the bowel of
young and aged patients undergoing major pancreatic surgical procedures.
    
    

Download PDF

Citation: César Machado MC, Silva FP and César Machado MA. Pancreatic Surgery in the Aged Population: Technical and Molecular Insights. Austin Pancreat Disord. 2017; 1(1): 1004.

Home

Journal Scope

Online First

Current Issue

Editorial Board

Instruction for Authors

Submit Your Article

Contact Us