ARE THERE DIFFERENCES IN LAPAROSCOPIC GASTRECTOMY MORBIDITY AND MORTALITY BETWEEN YOUNG AND OLDER?

ABSTRACT 
Background: Due to the longer life expectancy and consequently an increase in the elderly population, a higher incidence of gastric cancer is expected in this population in the coming decades. 
Aim: To compare the results of laparoscopic GC surgical treatment between individuals aged<65 years (group I) and ≥ 65 years (group II), according to clinical, surgical, and histopathological characteristics. 
Methods: A observational retrospective study was performed by analyzing medical charts of patients with gastric cancer undergoing total or subtotal laparoscopic gastrectomy for curative purposes by a single oncologic surgery team. 
Results: Thirty-six patients were included in each group. Regarding the ASA classification, 31% of the patients in group I was ASA 1, compared to 3.1% in group II. The mean number of concomitant medications in group II was statistically superior to group I (5±4.21 x 1.42±3.08, p<0.001). Subtotal gastrectomy was the most performed procedure in both groups (69.4% and 63.9% in groups I and II, respectively) due to the high prevalence of distal tumors in both groups, 54.4% group I and 52.9% group II. According to Lauren's classification, group I presented a predominance of diffuse tumors (50%) and group II the intestinal type (61.8%). There was no difference between the two groups regarding the number of resected lymph nodes and lymph node metastases and the days of hospitalization and mortality. 
Conclusion: Laparoscopic gastrectomy showed to be a safe procedure, without a statistical difference in morbidity, mortality, and hospitalization time between both groups.


INTRODUCTION
Gastric cancer (GC) is a common and lethal type of neoplasm worldwide. It is the 3 rd most frequent malignant tumor among Brazilian men and the 5 th among Brazilian women.
The overall prediction is that, by 2025, both the incidence of GC and its mortality decrease, with an increase in survival, reaching 30% in five years 25 .
The etiology is multifactorial, and among the known risk factors is the increase in age 10 .
According to data from the Brazilian Institute of Geography and Statistics (IBGE), by the year 2025, Brazil should have the 6 th largest elderly population globally, with approximately 32 million people, which will mean almost 13% of the Brazilian population 4 .
Among the elderly, age itself is a predictor of morbidity and mortality risk, leading to an increase of 1.35 in mortality risk at 30 days after non-cardiac surgery every decade 21 .
Radical gastrectomy is the only therapeutic approach capable of curing GC, and its application should be discussed regardless of age. It is a surgical procedure in which total or subtotal gastric resection is performed, with satisfactory surgical margins, associated with D2 lymphadenectomy, the resection of the perigastric extra-perigastric lymph nodes. This is considered the standard surgical procedure for the treatment of advanced GC 1 .
Previous studies have shown that distal and total laparoscopic gastrectomy is safe among the elderly 15,26 . However, the evidence regarding GC management is scarce in this age group and the Brazilian population. Therefore, given the higher incidence of CG in elderly populations and the progressive aging of the global population, especially in developing countries such as Brazil, it is necessary to research this medical issue more deeply.
This study aimed to investigate the short-term surgical morbimortality of laparoscopic GC gastrectomy in elderly patients compared to non-elderly patients to determine the safety, viability, and risk factors for postoperative complications associated with the surgical procedure.

METHODS
The Institutional Review Board approved this project following Resolution No. A cross-sectional, retrospective study was carried out by analyzing medical records and anatomopathological reports of patients with GC who underwent radical, subtotal, and total gastrectomy using a laparoscopic procedure for curative purposes in 5 years, attended by a single oncological surgery team. Patients with a diagnosis of GC of both genders were eligible. Patients with peritoneal carcinomatosis and distant metastases were excluded, which would contraindicate radical gastrectomy. Patients were stratified according to age as adults (≥18 and <65 years) and elderly (≥65 years) according to World Health Organization (WHO) criteria 29 .
The following variables were collected: 1) clinical-surgical: gender, age, smoking

Statistical analysis
Quantitative variables were presented as mean ± standard-deviation and were submitted to the Shapiro-Wilk normality test. To verify the association between two categorical variables, the chi-square tests of independence and Fisher exact and binary logistic regression model were used. The comparison of quantitative variables between the two groups was performed using the Wilcoxon Mann-Whitney test for independent samples. The analyses were developed in program R and were considered significant p<0.05.

RESULTS
A total of 72 medical charts, 36 patients aged <65 years (group I), and 36 patients aged ≥ 65 years (group II) were evaluated. Group I had 63.9% of women. In group II, most of the sample consisted of men. Group II had a higher frequency of smokers when compared to group I (45.5% vs. 4.2%, p<0.001).
Regarding the ASA classification, 93.2% of the patients were ASA 1 and 2 in group I.
Among individuals in group II, only 3.1% were ASA 1 and 59.4% ASA 2. The concomitant medications recorded in the medical charts were related to the treatment of psychiatric, cardiovascular, digestive, and endocrine comorbidities, and the use of antiparkinsonian and anti-inflammatory drugs was also reported. The mean number of concomitant medications in group II was statistically higher when compared to group I (p<0.001, Table   1).   The percentage of patients who evolved to death in groups I and II was 5.6% and 19.4%, respectively, without a statistical difference (Table 3).  The features of the nine patients that evolved to death are described in detail in Table 5.

DISCUSSION
GC is a public health problem, accounting for many deaths, and age is considered one of the independent factors for the increase in the incidence of GC 25,5 . All patients were submitted to laparoscopy gastrectomy, regardless of stage. Some studies comparing open and laparoscopy gastrectomy for advanced gastric cancer (T2 or more) concluded that laparoscopy surgery is a feasible treatment strategy for advanced gastric tumors and that experienced surgeons can safely perform laparoscopy with D2 lymphadenectomy for advanced GC 3 . Our data indicated that, as in other countries, Brazilian surgeons perform more and more laparoscopy gastrectomy for advanced tumors 2 .
Although preoperative clinical evaluation is a common practice, it must consider specific clinical aspects in the elderly. Many abnormal laboratory findings are less valuable than history and physical examination in predicting postoperative morbidity 8 . Nelen et al. 17 , in a study with patients with GC, showed that one of the most striking features that distinguish young and old patients is the number of comorbidities that each presents. In their study, 72% of the male patients over 80 years old had comorbidities. In the study presented here, the number and the type of concomitant medications were used as an indirect measure to estimate comorbidities. The group of elderly had a higher number of concomitant medications. Data from the literature indicate that in the preoperative evaluation of patients with GC, age should not be the main criterion in which treatment decisions are made, but rather the presence of comorbidities 13 .
Corroborating this data, we analyzed the ASA classification. In this study, ASA 1, a healthy patient, was more common in group I patients. However, the ASA 2 means patients with severe systemic disease with functional limitation were more prevalent in group II 7 .
The higher prevalence of ASA 2 can be justified by the high age group since, overall, chronic diseases begin in the elderly phase of life 24 . A study by Tegels et al. 23  The extent of resection in GC depends on the tumor's size and location, the depth of its invasion, and the histological type. In general, total gastrectomy is performed in proximal tumors, and the subtotal in distal ones, associated with D2 lymphadenectomy 11 . In both groups, subtotal gastrectomy was the mandatory surgery for most patients, probably due to the higher prevalence of distal tumors.
In both groups, free margins were obtained in most cases. A meta-analysis assessed whether total gastrectomy would provide better outcomes than subtotal gastrectomy for distal gastric cancer and showed that, despite postoperative mortality being similar, total gastrectomy for distal gastric cancer harmed overall survival at five years. Therefore, subtotal gastrectomy remains a recommendation for distal gastric cancer, either because of the absence of randomized multicenter trials or the limited size of studies that follow long-term surgical outcomes 20 .
In a meta-analysis, Pan et al.19, including 3275 patients with GC, observed that in the geriatric group, the number of resected lymph nodes was lower than that of young adults 13 but without a change in the rate of overall survival expectancy. This shows that lower oncological radicality in this population and the non-change in overall survival may be related to the absence of comorbidities. More radical surgical procedures with resection of a high number of lymph nodes were associated with higher postoperative complications.
It was observed in the present study that, in both groups, the extent of lymphadenectomy was similar. According to the American Joint Committee on Cancer (AJCC) guidelines, the minimum number of lymph nodes for adequate tumor staging was reached, also indicating the oncological radicality of the surgeries 9 . This data shows that the elderly population may have the same chances of cure and can be submitted to procedures similar to younger patients.
Previous studies have identified age as a predictive factor of postoperative morbidity after gastrectomy 14 . On the other hand, some authors did not observe this relationship and reported morbidity and mortality rates in elderly patients, similar to young patients 18 . Kim et al. 13 evaluated the surgical procedure in the elderly, reaffirming the safety of subtotal gastrectomy in this age group. Postoperative complications were observed but like those expected for younger patients 13 . This evidence was also observed in the present study since there was no statistically significant difference between days of ICU stay, hospitalization time, number of complications, and death among the assessed groups.
Concerning the patients that died, there was no relative difference between the analyzed variables (gender, ASA, smoking history, anesthetic technique, tumor location, and positive lymph node presence) between the two groups, except the histological type of Laurén and the final staging. More common distal tumors in the patients evolved to death in group I and medial and proximal in group II. Tumor staging IIIB was the most common in group I and group II tumor stages IB and IIB. Regardless of age, tumor staging is an independent prognostic factor for overall survival and cancer-specific survival 16 , but in this study, long-term survival was not evaluated but instead in the postoperative period. Even statistically not different, the postoperative death rate of 19.4% in the elderly group is very expressive. The Elderly is regarded as being at increased risk during major abdominal surgery because of a lack of functional reserve and an increased number of comorbidities 21 .
When postoperative complications were evaluated, all patients in group I had sepsis.
A Chinese meta-analysis evaluated 2482 patients undergoing GC gastrectomy, and postoperative complications occurred in 8.9% of the cohort, with the most common being those related to infectious processes such as intra-abdominal infection, anastomotic extravasation, ascites, intra-abdominal bleeding, infection pulmonary and pleural effusion 30 .
Group II presented sepsis associated with renal complications. Acute kidney injury is known to be a complication associated with high morbidity and mortality in hospitalized patients 28 . It is not only one of the most common postoperative complications, especially after gastrectomy, but it is also associated with in-hospital mortality, long-term mortality after surgery, and an increased risk of progression to chronic kidney disease and renal failure 12 .
Some limitations are inherent to this study, mainly because it is a retrospective design with a small sample. Pre-anesthetic evaluations were performed in an out-of-hospital setting leading to data loss.

CONCLUSIONS
The results of this study indicate that laparoscopic gastrectomy, performed by qualified and well-trained surgeons, is a safe procedure, with no differences in morbidity and length of hospitalization among young and elderly patients. Advanced tumor staging and comorbidities were related to surgical mortality. The radicality of surgical treatment was equal regardless of age.