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Surgical outcomes and survival after gastrectomy in octogenarians with gastric cancer
j o u r n a l o f s u r g i c a l r e s e a r c h 1 9 8 ( 2 0 1 5 ) 8 0 e8 6
Available online at www.sciencedirect.com
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Surgical outcomes and survival after gastrectomy in octogenarians with gastric cancer Ji-Hyun Kim, MD, Hyung-Min Chin, MD, PhD, and Kyong-Hwa Jun, MD, PhD* Department of Surgery, St. Vincent’s Hospital, College of Medicine, Catholic University of Korea, Seoul, Republic of Korea
article info
abstract
Article history:
Background: The aim of this study was to evaluate the surgical outcomes and survival after
Received 10 April 2015
gastrectomy in octogenarians and identify the optimal treatment for these patients.
Received in revised form
Methods: The medical records of 1262 patients with gastric cancer who underwent
14 May 2015
gastrectomy from January 2003 to December 2012 were reviewed retrospectively. Patients
Accepted 22 May 2015
were divided into two age groups: octogenarians (80 y, n ¼ 75) and nonoctogenarians
Available online 29 May 2015
(<80 y, n ¼ 1187). The patients’ clinicopathologic data, surgical outcomes, and survival were evaluated.
Keywords:
Results: Octogenarians exhibited a higher proportion of female patients, poorer perfor-
Gastric cancer
mance scale scores, higher comorbidities, and more advanced tumorenodeemetastasis
Octogenarian
(TNM) stages than did nonoctogenarians. There was no difference in the surgical curability
Surgical outcome
between the two groups, although octogenarians were more likely to have higher post-
Survival
operative morbidity and mortality than those of nonoctogenarians. In an analysis of risk factors affecting survival after gastrectomy for octogenarians, only advanced TNM stage was an independent prognostic factor. Overall survival was significantly lower in octogenarians than in nonoctogenarians, whereas disease-specific survival was comparable between the two groups. There was no difference in the disease-specific survival for each stage of cancer after adjustment for tumor stage. Conclusions: Octogenarians had higher postoperative morbidity and mortality rates but comparable cancer-specific survival compared with nonoctogenarians. Only an advanced TNM stage influenced the prognosis of octogenarians. Early detection and thorough postoperative care would improve the overall survival for octogenarians with gastric cancer. ª 2015 Elsevier Inc. All rights reserved.
1.
Introduction
The worldwide incidence and mortality of gastric cancer have fallen dramatically during the past several decades. Nonetheless, gastric cancer is the fourth most common cancer and the second leading cause of cancer death worldwide, thus remaining a major public health issue [1]. Treatment
guidelines for gastric cancer have been issued, and a standard therapeutic strategy for gastric cancer according to stage has been established. Gastrectomy with D2 lymph node dissection has been increasingly regarded as the standard surgical procedure for most patients with operable gastric cancer [2,3]. With the aging of the population, 10%e20% of patients with gastric cancer in developed countries are aged 80 y [4].
* Corresponding author. Department of Surgery, St. Vincent’s Hospital, College of Medicine, Catholic University of Korea, 93-6, Ji-dong, Paldal-gu, Suwon, Gyeonggi-do 442-723, Republic of Korea. Tel.: þ82 31 249 7170; fax: þ82 31 247 5347. E-mail address: [email protected] (K.-H. Jun). 0022-4804/$ e see front matter ª 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jss.2015.05.046
j o u r n a l o f s u r g i c a l r e s e a r c h 1 9 8 ( 2 0 1 5 ) 8 0 e8 6
Although the living conditions and quality of medical care have dramatically improved in many countries, most patients in this age group have comorbidities such as cardiovascular disease and renal or respiratory dysfunction. Some studies have reported that gastrectomy with curative intent for elderly patients is associated with increased postoperative morbidity and mortality [5,6], whereas other studies have reported that elderly patients can safely undergo gastrectomy [7]. Thus, no consensus has been established on whether these therapeutic strategies are appropriate for treating gastric cancer in elderly patients, especially octogenarians, and controversy still exists. In the present study, we compared the clinicopathologic findings and surgical outcomes of gastric cancer between octogenarians and nonoctogenarians. We also investigated risk factors and survival to identify the optimal treatment regimen for octogenarians with gastric cancer.
2.
Patients and methods
2.1.
Patients
A total of 1262 patients with gastric cancer who underwent gastrectomy from January 2003 to December 2012 at St. Vincent’s Hospital, the Catholic University of Korea were enrolled in this retrospective study. Patients with a history of gastric surgery, neoadjuvant chemotherapy, or palliative procedures such as bypass surgery or exploratory laparotomy were excluded. The patients were classified into two age groups: octogenarians (aged 80 y, n ¼ 75) and nonoctogenarians (aged <80 y, n ¼ 1187). Clinical, surgical, and pathologic data were obtained from the hospital records. The Institutional Review Board of St. Vincent’s Hospital approved this study (VC14RISI0112). All patients underwent subtotal gastrectomy or total gastrectomy with regional lymph node dissection (D1 plus or D2) according to the Guidelines of the Japanese Research Society for Gastric Cancer [2] .The cancer stage and histopathologic classification were based on the seventh edition of the American Joint Committee on Cancer staging system [8]. Postoperative chemotherapy was implemented according to the tumorenodeemetastasis (TNM) stage, physical condition, and willingness of the patient. The chemotherapeutic regimen comprised 5-fluorouracil and cisplatin. The clinicopathologic features evaluated included age, sex, Eastern cooperative oncology group performance status, number of comorbidities, type of gastrectomy, depth of invasion, lymph node metastasis, TNM stage, extent of lymphadenectomy, number of retrieved lymph nodes, curability, operation time, blood loss, and hospital stay. The postoperative complications were classified as surgical or medical complications. Anastomotic leakage, postoperative bleeding, anastomotic stenosis, intraabdominal abscess, afferent loop syndrome, wound infection, and ileus were defined as surgical procedureerelated complications, whereas pulmonary disease, cardiovascular disease, and systemic infections were considered to be medical complications. Late complications, such as anemia and dumping, were not included in this study.
81
Thirty-day mortality was defined as postoperative death of any cause within 30 d of surgery. All patients were followed up every 6 mo for 2 y after surgery, every year for up to 5 y, and then every year until the end of the study period or death. Physical examination, laboratory tests, imaging, and endoscopy were performed at every visit. The median follow-up period was 43.7 mo (range, 0.1e97.0 mo). The follow-up data were used to calculate the overall and disease-specific survival rates as of December 2013.
2.2.
Statistical analysis
Discrete or categorical variables are expressed as counts and percentages and continuous variables as means standard deviations. The chi-squared test or Fisher exact test was used to compare discrete or categorical variables, and the Student ttest was used for continuous variables. Overall survival was estimated by the KaplaneMeier method, and the log-rank test was used to compare survival curves. Multivariable analysis for independent risk factors was performed using the logistic regression test, and Cox proportional hazard models were used to obtain the hazard ratio. A P value of <0.05 was considered to indicate a statistically significant difference with a 95% confidence interval. Statistical analysis was conducted using SPSS version 21 (SPSS Inc, Chicago, IL).
3.
Results
3.1.
Clinicopathologic characteristics
The clinicopathologic characteristics of the two study groups are shown in Table 1. The mean age was 82.2 2.3 y (range, 80e89 y) among the octogenarians and 59.8 11.8 y (range, 22e79 y) among the nonoctogenarians. The octogenarians exhibited a higher proportion of female patients, poorer Eastern cooperative oncology group scores, and higher comorbidities. There were no differences in the type of gastrectomy or extent of lymphadenectomy between the two groups. In terms of cancer invasion, octogenarians were more likely to have advanced T stage, N stage, and TNM stage cancer. Furthermore, the proportion of octogenarians with T3 and T4 stage cancer was higher than that of nonoctogenarians (60.0% versus 36.8%, respectively; P < 0.001). There was no difference in the surgical curability between the two groups; however, shorter operation times and fewer numbers of retrieved lymph nodes were found in octogenarians than in nonoctogenarians. Blood loss during the operation was comparable between the two groups, whereas longer hospital stays occurred among octogenarians compared with nonoctogenarians.
3.2.
Postoperative complications
Table 2 summarizes the postoperative morbidity and mortality. Surgical and medical complication rates were all higher in octogenarians than in nonoctogenarians. The rates of surgical complications in octogenarians and nonoctogenarians were 16.0% and 7.5%, respectively (P ¼ 0.008), and those of medical complications were 14.6% and 2.5%, respectively (P < 0.001). The most common surgical complications in octogenarians
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j o u r n a l o f s u r g i c a l r e s e a r c h 1 9 8 ( 2 0 1 5 ) 8 0 e8 6
Table 1 e Clinicopathologic characteristics of the patients.
Age (y) Sex Male Female Eastern cooperative oncology group 0 1 2 3 or 4 No. of comorbidities 0 1 2 3 Type of operation Subtotal gastrectomy Total gastrectomy Depth of invasion pT1 pT2 pT3 pT4 Lymph node metastasis Negative Positive TNM stage I II III IV Lymph node dissection D1þ D2 Number of retrieved lymph nodes Curability Curative Palliative Operation time (min) Blood loss (mL) Hospital stay (d)
Nonoctogenarian
Octogenarian
P value
(n ¼ 1187)
(n ¼ 75)
59.8 11.8
82.2 2.3
778 (65.5) 409 (34.5)
40 (53.3) 35 (46.7)
0.015
<0.001
1166 6 10 5
(98.2) (0.5) (0.8) (0.5)
35 (86.7) 2 (2.7) 7 (9.3) 1 (1.3)
<0.001
691 360 123 13
(58.2) (30.3) (10.4) (1.1)
30 (40.0) 27 (36.0) 16 (21.3) 2 (2.7)
0.003
863 (72.7) 324 (27.3)
57 (76.0) 18 (24.0)
0.594
612 138 213 224
(51.6) (11.6) (17.9) (18.9)
20 (26.7) 10 (13.3) 26 (34.7) 19 (25.3)
<0.001
739 (62.0) 451 (38.0)
37 (49.3) 38 (50.7)
0.029
672 210 271 34
25 (33.3) 22 (29.3) 26 (34.7) 2 (2.7)
<0.001
(56.6) (17.7) (22.8) (2.9)
341 (28.7) 846 (71.3) 32.7 13.9
23 (30.7) 52 (69.3) 27.7 13.7
1091 (91.9) 96 (8.1) 254.9 61.3 382.9 221.8 14.37 8.8
67 (89.3) 8 (10.7) 230.1 68.9 363.5 227.8 19.6 16.5
0.719 <0.001 0.431 <0.001 0.233 <0.001
Values in parentheses are percentage.
were anastomotic leakage and anastomotic stenosis (both n ¼ 3, 4.0%), and the most common surgical complication in nonoctogenarians was gastric stasis (n ¼ 23, 1.9%). The most common type of medical complication in both groups was pulmonary in nature (pneumonia or pleural effusion). Octogenarians had higher 30-d mortality rates than those of nonoctogenarians (4.0% versus 0.3%, respectively; P ¼ 0.004). All the 30-d mortality patients had medical complications, one acute respiratory distress syndrome, one cerebrovascular accident, and one atrial fibrillation and septic shock. At the median follow-up of 43.7 mo (range, 0.1e97.0 mo), cancer recurred in 194 patients (15.4%) (14 octogenarians [18.7%] and 180 nonoctogenarians [15.2%]; P ¼ 0.415). Nonecancer-related deaths accounted for 29.3% and 7.7% of octogenarian and nonoctogenarian deaths, respectively (P < 0.001). There was no significant difference in cancer-related deaths between the two groups (13.3% versus 12.4%; P ¼ 0.809).
3.3. Survival between octogenarians and nonoctogenarians The overall survival was significantly lower in octogenarians than in nonoctogenarians (P < 0.001) (Fig. 1). However, diseasespecific survival was comparable between the two groups (P ¼ 0.262) (Fig. 2). When adjusted for TNM stage, no statistically significant difference was observed among patients with stage I (P ¼ 0.662) (Fig. 3A), stage II (P ¼ 0.171) (Fig. 3B), stage III (P ¼ 0.165) (Fig. 3C), and stage IV (P ¼ 0.673) (Fig. 3D).
3.4.
Prognostic factors in octogenarians
Univariate and multivariate analyses were performed to detect prognostic factors for octogenarians undergoing curative resection. Univariate analysis revealed that the depth of invasion (T3), lymph node metastasis (positive), and TNM
j o u r n a l o f s u r g i c a l r e s e a r c h 1 9 8 ( 2 0 1 5 ) 8 0 e8 6
83
Table 2 e Postoperative morbidities in each group. Nonoctogenarian Octogenarian
Surgical complications Leakage Bleeding Stenosis Intraabdominal abscess A-loop syndrome Gastric stasis Ileus Wound infection Others* Medical complications Pulmonary disease Cardiovascular disease Systemic infections Othersy Total complications
(n ¼ 1187)
(n ¼ 75)
89 (7.5)
12 (16.0)
P value 0.008
19 9 6 2
(1.6) (0.8) (0.5) (0.2)
3 1 3 2
(4.0) (1.3) (4.0) (2.7)
0.138 1.000 0.013 0.019
1 23 20 6 3 30
(0.1) (1.9) (1.7) (0.5) (0.1) (2.5)
0 2 1 0 0 11
(0) (2.7) (1.3) (0) (0) (14.6)
1.000 0.657 1.000 1.000 1.000 <0.001
28 (2.4) 1 (0.1)
8 (10.7) 1 (1.3)
0.001 0.115
0 (0) 1 (0.1) 119 (10.3)
1 (1.3) 1 (1.3) 23 (30.6)
0.059 0.115 <0.001
Values in parentheses are percentages. * Chyle. y Infectious colitis, delirium.
stage (III) significantly affected prognosis in octogenarians (Table 3), whereas multivariate analysis identified only TNM stage (III) as an independent prognostic factor (hazard ratio, 4.096; 95% confidence interval, 1.703e9.851; P ¼ 0.002).
4.
Discussion
The proportion of elderly patients diagnosed with malignancies has been increasing, although the prevalence of
Fig. 1 e Overall survival of octogenarians and nonoctogenarians after curative resection. (Color version of figure is available online.)
Fig. 2 e Disease-specific survival of octogenarians and nonoctogenarians after curative resection. (Color version of figure is available online.)
gastric cancer has approached a plateau or even slightly decreased in recent years [9]. In general, elderly patients have complicated comorbidities and decreased organ reserve; as a result, the postoperative morbidity and mortality rates after gastrectomy with curative intent are higher in elderly than in young patients. Although several recent studies have demonstrated that advances in surgical and anesthetic techniques have reduced perioperative complications and improved short-term surgical outcomes in elderly patients [10e12], many surgeons have some doubts concerning the benefit of curative resection for elderly patients with gastric cancer. Arai et al. [13] evaluated the characteristics of gastric cancer of a large cohort of elderly patients. They found that the relative odds of gastric cancer were higher in men than in women for all age groups, whereas the male-to-female ratio significantly decreased with advancing age, and the early to advanced cancer ratios were approximately equal in all age groups. Other studies have found no significant positive correlation between age and advanced clinical stage in patients with gastric cancer [7,14]. Liang et al. [15] reported that elderly patients were more likely to have more advanced TNM stages and larger tumor sizes. In the present study, octogenarians had a lower male-to-female ratio, deeper invasion, more frequent lymph node metastasis, and more advanced TNM stages. However, these findings cannot simply be interpreted as a correlation between age and advanced stage. Hayashi et al. [16] reported that the rate of diagnosis of gastric cancer in a cancer-screening program was lower in elderly patients (9.1%, aged 65 y) than in nonelderly patients (15.6%, aged <65 y). They also found that nongastric cancer-specific symptoms such as anorexia, dizziness, nausea, fatigue, and weight loss were more frequent in elderly patients than in nonelderly patients. Thus, a delayed diagnosis of gastric cancer is assumed to be a possible cause of the higher TNM stages seen in elderly patients. Greater efforts to establish cancer-screening programs in elderly patients, including
84
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Fig. 3 e Disease-specific survival of each age group according to TNM stage: (A) stage I, (B) stage II, (C) stage III, and (D) stage IV. (Color version of figure is available online.)
octogenarians, would help lower their stage of gastric cancer at diagnosis, leading to a survival benefit. With respect to surgical treatment, curative resection with adequate lymph node dissection is the most important factor for long-term survival in patients with gastric cancer [16]. In the present study, octogenarians were more likely to have shorter operation times and fewer retrieved lymph nodes than nonoctogenarians, although there was no significant difference in either the curative resection rate (89.3% versus 91.9%, respectively) or the D1/D2 dissection ratio (30.7%:69.3% versus 28.7%:71.3%, respectively). These results are comparable with those of other studies, in which the curative resection rates ranged from 52%e77% in patients aged 80 y [17e19]. However, the survival benefit of D2 lymph node dissection for elderly patients with gastric cancer remains unproven in consideration of postoperative complications and life expectancy. Respiratory and immunologic functions tend to decrease with advancing age, resulting in a higher risk of postoperative complications, such as pneumonia and systemic infections [20]. Although some previous studies found no differences in postoperative morbidity and mortality rates between elderly and nonelderly patients [21e23], others
reported significantly higher rates in elderly patients because of preexisting comorbidities or unrecognized frailty [6,16]. Frailty represents a state of increased vulnerability to stressors, leading to a heightened risk of adverse outcomes. The exhibition of frailty in the elderly population could partly explain their increased morbidity and 30-d mortality. In the present study, octogenarians had longer hospital stays and higher postoperative morbidity and mortality rates than those of nonoctogenarians. Hence, more attention should be given to the treatment of other comorbid diseases to improve the outcome of gastric cancer in octogenarians. Many studies that analyzed the surgical outcomes of elderly patients with gastric cancer found that depth of invasion, lymph node metastasis, and distant metastasis were independent prognostic factors [15,21,24]. Pisanu et al. [10] demonstrated that tumor stage was the only prognostic factor influencing survival for patients aged 75 y. Our results are consistent with these reports and showed that TNM stage was an independent prognostic factor for octogenarians. Survival has also been investigated in many previous studies. Most reported that although the overall survival of elderly patients was significantly lower than that of nonelderly patients, there
85
j o u r n a l o f s u r g i c a l r e s e a r c h 1 9 8 ( 2 0 1 5 ) 8 0 e8 6
Table 3 e Univariate and multivariate analyses of prognostic factors for octogenarians undergoing gastrectomy. Characteristics
Univariate analysis 3-y Overall survival
Sex Male Female Eastern cooperative oncology group 0 1 No. of comorbidities 0 1 2 Type of operation Subtotal gastrectomy Total gastrectomy Depth of invasion pT1/pT2 pT3/pT4 Lymph node metastasis Negative Positive TNM stage I/II III/IV Lymph node dissection D1þ D2 Complications No Yes
5-y Overall survival
P value
Hazard ratio (95% confidence interval)
P value
51.5 62.3
33.8 53.4
0.312
60.8 24.0
43.4 24.0
0.176
1.997 (0.673e5.926)
0.212
56.9 68.3 37.0
32.0 68.3 0.2
0.199
1.547 (0.634e3.779)
0.338
66.2 48.7
19.0 48.7
0.959
38.7 34.1
38.7 11.7
<0.001
4.096 (1.703e9.851)
0.074
59.5 20.9
59.5 0
0.002
75.0 66.7
23.3 0
<0.001
4.096 (1.703e9.851)
0.002
60.1 57.8
60.1 34.0
0.390
59.4 49.6
40.2 49.6
0.190
2.096 (0.814e5.402)
0.125
was no difference in the disease-specific survival. In particular, because octogenarians had more advanced TNM stages than did nonoctogenarians in the present study, we also analyzed survival according to TNM stage to prevent bias related to stage-related mortality. We found no differences in survival at each stage between octogenarians and nonoctogenarians. According to Mita et al. [21], these results suggest that elderly patients undergoing curative resection for gastric cancer have the same chance of survival as do nonelderly patients. Additionally, the TNM stage of octogenarians was significantly higher; thus, a greater effort toward early detection of cancer can lead to the need for less aggressive surgery and better surgical outcomes. There are some limitations of this study. First, there may have been bias in the patient selection, because our data were obtained retrospectively from a single institution. Regional or population distribution differences also cannot be disregarded. Second, we did not analyze the survival of octogenarians according to the extent of lymph node dissection; therefore, the most appropriate extent of surgery with curative intent remains unclear. Additional well-designed, large cohort studies are needed to clarify this issue.
5.
Multivariate analysis
Conclusions
Octogenarians had higher postoperative morbidity and mortality rates but their cancer-specific survival was comparable
with that of nonoctogenarians. The only independent prognostic factor was TNM stage; neither performance scale nor comorbidities had an impact on prognosis. There is a need to pay more attention to early detection because equivalent long-term survival is achievable in the selected octogenarians. Careful patient selection is also important in those with advanced stage.
Acknowledgment Author contributions: K.H.J., J.H.K., and H.M.C. designed the research; J.H.K., K.H.J. performed the research; K.H.J. and H.M.C. analyzed the data; and K.H.J. and J.H.K. wrote the manuscript.
Disclosure The authors declare that there are no conflicts of interest.
references
[1] Crew KD, Neugut AI. Epidemiology of gastric cancer. World J Gastroenterol 2006;12:354.
86
j o u r n a l o f s u r g i c a l r e s e a r c h 1 9 8 ( 2 0 1 5 ) 8 0 e8 6
[2] Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2010 (ver. 3). Gastric Cancer 2011;14: 113. [3] Degiuli M, Sasako M, Ponti A. Morbidity and mortality in the Italian Gastric Cancer Study Group randomized clinical trial of D1 versus D2 resection for gastric cancer. Br J Surg 2010;97: 643. [4] Dudeja V, Habermann EB, Zhong W, et al. Guideline recommended gastric cancer care in the elderly: insights into the applicability of cancer trials to real world. Ann Surg Oncol 2011;18:26. [5] Bittner R, Butters M, Ulrich M, Uppenbrink S, Beger HG. Total gastrectomy. Updated operative mortality and long-term survival with particular reference to patients older than 70 years of age. Ann Surg 1996;224:37. [6] Eguchi T, Takahashi Y, Ikarashi M, Kasahara M, Fujii M. Is extended lymph node dissection necessary for gastric cancer in elderly patients? Eur J Surg 2000;166:949. [7] Takeshita H, Ichikawa D, Komatsu S, et al. Surgical outcomes of gastrectomy for elderly patients with gastric cancer. World J Surg 2013;37:2891. [8] Washington K. 7th Edition of the AJCC cancer staging manual: stomach. Ann Surg Oncol 2010;17:3077. [9] Bray F, Jemal A, Grey N, Ferlay J, Forman D. Global cancer transitions according to the Human Development Index (2008-2030): a population-based study. Lancet Oncol 2012;13: 790. [10] Pisanu A, Montisci A, Piu S, Uccheddu A. Curative surgery for gastric cancer in the elderly: treatment decisions, surgical morbidity, mortality, prognosis and quality of life. Tumori 2007;93:478. [11] Fujiwara S, Noguchi T, Harada K, Noguchi T, Wada S, Moriyama H. How should we treat gastric cancer in the very elderly? Hepatogastroenterology 2012;59:620. [12] Dittmar Y, Rauchfuss F, Gotz M, Scheuerlein H, Jandt K, Settmacher U. Impact of clinical and pathohistological
[13]
[14]
[15]
[16]
[17] [18]
[19]
[20] [21]
[22]
[23]
[24]
characteristics on the incidence of recurrence and survival in elderly patients with gastric cancer. World J Surg 2012;36:338. Arai T, Esaki Y, Inoshita N, et al. Pathologic characteristics of gastric cancer in the elderly: a retrospective study of 994 surgical patients. Gastric Cancer 2004;7:154. Holmes FF, Hearne E 3rd. Cancer stage-to-age relationship: implications for cancer screening in the elderly. J Am Geriatr Soc 1981;29:55. Liang YX, Deng JY, Guo HH, et al. Characteristics and prognosis of gastric cancer in patients aged 70 years. World J Gastroenterol 2013;19:6568. Hayashi T, Yoshikawa T, Aoyama T, Ogata T, Cho H, Tsuburaya A. Severity of complications after gastrectomy in elderly patients with gastric cancer. World J Surg 2012;36: 2139. Eguchi T, Fujii M, Takayama T. Mortality for gastric cancer in elderly patients. J Surg Oncol 2003;84:132. Kitamura K, Sugimachi K, Saku M. Evaluation of surgical treatment for patients with gastric cancer who are over 80 years of age. Hepatogastroenterology 1999;46:2074. Hanazaki K, Wakabayashi M, Sodeyama H, et al. Surgery for gastric cancer in patients older than 80 years of age. Hepatogastroenterology 1998;45:268. Vallejo AN. Immunological hurdles of ageing: indispensable research of the human model. Ageing Res Rev 2011;10:315. Mita K, Ito H, Hashimoto M, et al. Postoperative complications and survival after gastric cancer surgery in patients older than 80 years of age. J Gastrointest Surg 2013;17:2067. Orsenigo E, Tomajer V, Palo SD, et al. Impact of age on postoperative outcomes in 1118 gastric cancer patients undergoing surgical treatment. Gastric Cancer 2007;10:39. Saidi RF, Bell JL, Dudrick PS. Surgical resection for gastric cancer in elderly patients: is there a difference in outcome? J Surg Res 2004;118:15. Yokota T, Kunii Y, Saito T, et al. Prognostic factors for gastric cancer in the elderly. Eur J Surg Oncol 2001;27:451.
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.JournalofSurgicalResearch.com
Surgical outcomes and survival after gastrectomy in octogenarians with gastric cancer Ji-Hyun Kim, MD, Hyung-Min Chin, MD, PhD, and Kyong-Hwa Jun, MD, PhD* Department of Surgery, St. Vincent’s Hospital, College of Medicine, Catholic University of Korea, Seoul, Republic of Korea
article info
abstract
Article history:
Background: The aim of this study was to evaluate the surgical outcomes and survival after
Received 10 April 2015
gastrectomy in octogenarians and identify the optimal treatment for these patients.
Received in revised form
Methods: The medical records of 1262 patients with gastric cancer who underwent
14 May 2015
gastrectomy from January 2003 to December 2012 were reviewed retrospectively. Patients
Accepted 22 May 2015
were divided into two age groups: octogenarians (80 y, n ¼ 75) and nonoctogenarians
Available online 29 May 2015
(<80 y, n ¼ 1187). The patients’ clinicopathologic data, surgical outcomes, and survival were evaluated.
Keywords:
Results: Octogenarians exhibited a higher proportion of female patients, poorer perfor-
Gastric cancer
mance scale scores, higher comorbidities, and more advanced tumorenodeemetastasis
Octogenarian
(TNM) stages than did nonoctogenarians. There was no difference in the surgical curability
Surgical outcome
between the two groups, although octogenarians were more likely to have higher post-
Survival
operative morbidity and mortality than those of nonoctogenarians. In an analysis of risk factors affecting survival after gastrectomy for octogenarians, only advanced TNM stage was an independent prognostic factor. Overall survival was significantly lower in octogenarians than in nonoctogenarians, whereas disease-specific survival was comparable between the two groups. There was no difference in the disease-specific survival for each stage of cancer after adjustment for tumor stage. Conclusions: Octogenarians had higher postoperative morbidity and mortality rates but comparable cancer-specific survival compared with nonoctogenarians. Only an advanced TNM stage influenced the prognosis of octogenarians. Early detection and thorough postoperative care would improve the overall survival for octogenarians with gastric cancer. ª 2015 Elsevier Inc. All rights reserved.
1.
Introduction
The worldwide incidence and mortality of gastric cancer have fallen dramatically during the past several decades. Nonetheless, gastric cancer is the fourth most common cancer and the second leading cause of cancer death worldwide, thus remaining a major public health issue [1]. Treatment
guidelines for gastric cancer have been issued, and a standard therapeutic strategy for gastric cancer according to stage has been established. Gastrectomy with D2 lymph node dissection has been increasingly regarded as the standard surgical procedure for most patients with operable gastric cancer [2,3]. With the aging of the population, 10%e20% of patients with gastric cancer in developed countries are aged 80 y [4].
* Corresponding author. Department of Surgery, St. Vincent’s Hospital, College of Medicine, Catholic University of Korea, 93-6, Ji-dong, Paldal-gu, Suwon, Gyeonggi-do 442-723, Republic of Korea. Tel.: þ82 31 249 7170; fax: þ82 31 247 5347. E-mail address: [email protected] (K.-H. Jun). 0022-4804/$ e see front matter ª 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jss.2015.05.046
j o u r n a l o f s u r g i c a l r e s e a r c h 1 9 8 ( 2 0 1 5 ) 8 0 e8 6
Although the living conditions and quality of medical care have dramatically improved in many countries, most patients in this age group have comorbidities such as cardiovascular disease and renal or respiratory dysfunction. Some studies have reported that gastrectomy with curative intent for elderly patients is associated with increased postoperative morbidity and mortality [5,6], whereas other studies have reported that elderly patients can safely undergo gastrectomy [7]. Thus, no consensus has been established on whether these therapeutic strategies are appropriate for treating gastric cancer in elderly patients, especially octogenarians, and controversy still exists. In the present study, we compared the clinicopathologic findings and surgical outcomes of gastric cancer between octogenarians and nonoctogenarians. We also investigated risk factors and survival to identify the optimal treatment regimen for octogenarians with gastric cancer.
2.
Patients and methods
2.1.
Patients
A total of 1262 patients with gastric cancer who underwent gastrectomy from January 2003 to December 2012 at St. Vincent’s Hospital, the Catholic University of Korea were enrolled in this retrospective study. Patients with a history of gastric surgery, neoadjuvant chemotherapy, or palliative procedures such as bypass surgery or exploratory laparotomy were excluded. The patients were classified into two age groups: octogenarians (aged 80 y, n ¼ 75) and nonoctogenarians (aged <80 y, n ¼ 1187). Clinical, surgical, and pathologic data were obtained from the hospital records. The Institutional Review Board of St. Vincent’s Hospital approved this study (VC14RISI0112). All patients underwent subtotal gastrectomy or total gastrectomy with regional lymph node dissection (D1 plus or D2) according to the Guidelines of the Japanese Research Society for Gastric Cancer [2] .The cancer stage and histopathologic classification were based on the seventh edition of the American Joint Committee on Cancer staging system [8]. Postoperative chemotherapy was implemented according to the tumorenodeemetastasis (TNM) stage, physical condition, and willingness of the patient. The chemotherapeutic regimen comprised 5-fluorouracil and cisplatin. The clinicopathologic features evaluated included age, sex, Eastern cooperative oncology group performance status, number of comorbidities, type of gastrectomy, depth of invasion, lymph node metastasis, TNM stage, extent of lymphadenectomy, number of retrieved lymph nodes, curability, operation time, blood loss, and hospital stay. The postoperative complications were classified as surgical or medical complications. Anastomotic leakage, postoperative bleeding, anastomotic stenosis, intraabdominal abscess, afferent loop syndrome, wound infection, and ileus were defined as surgical procedureerelated complications, whereas pulmonary disease, cardiovascular disease, and systemic infections were considered to be medical complications. Late complications, such as anemia and dumping, were not included in this study.
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Thirty-day mortality was defined as postoperative death of any cause within 30 d of surgery. All patients were followed up every 6 mo for 2 y after surgery, every year for up to 5 y, and then every year until the end of the study period or death. Physical examination, laboratory tests, imaging, and endoscopy were performed at every visit. The median follow-up period was 43.7 mo (range, 0.1e97.0 mo). The follow-up data were used to calculate the overall and disease-specific survival rates as of December 2013.
2.2.
Statistical analysis
Discrete or categorical variables are expressed as counts and percentages and continuous variables as means standard deviations. The chi-squared test or Fisher exact test was used to compare discrete or categorical variables, and the Student ttest was used for continuous variables. Overall survival was estimated by the KaplaneMeier method, and the log-rank test was used to compare survival curves. Multivariable analysis for independent risk factors was performed using the logistic regression test, and Cox proportional hazard models were used to obtain the hazard ratio. A P value of <0.05 was considered to indicate a statistically significant difference with a 95% confidence interval. Statistical analysis was conducted using SPSS version 21 (SPSS Inc, Chicago, IL).
3.
Results
3.1.
Clinicopathologic characteristics
The clinicopathologic characteristics of the two study groups are shown in Table 1. The mean age was 82.2 2.3 y (range, 80e89 y) among the octogenarians and 59.8 11.8 y (range, 22e79 y) among the nonoctogenarians. The octogenarians exhibited a higher proportion of female patients, poorer Eastern cooperative oncology group scores, and higher comorbidities. There were no differences in the type of gastrectomy or extent of lymphadenectomy between the two groups. In terms of cancer invasion, octogenarians were more likely to have advanced T stage, N stage, and TNM stage cancer. Furthermore, the proportion of octogenarians with T3 and T4 stage cancer was higher than that of nonoctogenarians (60.0% versus 36.8%, respectively; P < 0.001). There was no difference in the surgical curability between the two groups; however, shorter operation times and fewer numbers of retrieved lymph nodes were found in octogenarians than in nonoctogenarians. Blood loss during the operation was comparable between the two groups, whereas longer hospital stays occurred among octogenarians compared with nonoctogenarians.
3.2.
Postoperative complications
Table 2 summarizes the postoperative morbidity and mortality. Surgical and medical complication rates were all higher in octogenarians than in nonoctogenarians. The rates of surgical complications in octogenarians and nonoctogenarians were 16.0% and 7.5%, respectively (P ¼ 0.008), and those of medical complications were 14.6% and 2.5%, respectively (P < 0.001). The most common surgical complications in octogenarians
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Table 1 e Clinicopathologic characteristics of the patients.
Age (y) Sex Male Female Eastern cooperative oncology group 0 1 2 3 or 4 No. of comorbidities 0 1 2 3 Type of operation Subtotal gastrectomy Total gastrectomy Depth of invasion pT1 pT2 pT3 pT4 Lymph node metastasis Negative Positive TNM stage I II III IV Lymph node dissection D1þ D2 Number of retrieved lymph nodes Curability Curative Palliative Operation time (min) Blood loss (mL) Hospital stay (d)
Nonoctogenarian
Octogenarian
P value
(n ¼ 1187)
(n ¼ 75)
59.8 11.8
82.2 2.3
778 (65.5) 409 (34.5)
40 (53.3) 35 (46.7)
0.015
<0.001
1166 6 10 5
(98.2) (0.5) (0.8) (0.5)
35 (86.7) 2 (2.7) 7 (9.3) 1 (1.3)
<0.001
691 360 123 13
(58.2) (30.3) (10.4) (1.1)
30 (40.0) 27 (36.0) 16 (21.3) 2 (2.7)
0.003
863 (72.7) 324 (27.3)
57 (76.0) 18 (24.0)
0.594
612 138 213 224
(51.6) (11.6) (17.9) (18.9)
20 (26.7) 10 (13.3) 26 (34.7) 19 (25.3)
<0.001
739 (62.0) 451 (38.0)
37 (49.3) 38 (50.7)
0.029
672 210 271 34
25 (33.3) 22 (29.3) 26 (34.7) 2 (2.7)
<0.001
(56.6) (17.7) (22.8) (2.9)
341 (28.7) 846 (71.3) 32.7 13.9
23 (30.7) 52 (69.3) 27.7 13.7
1091 (91.9) 96 (8.1) 254.9 61.3 382.9 221.8 14.37 8.8
67 (89.3) 8 (10.7) 230.1 68.9 363.5 227.8 19.6 16.5
0.719 <0.001 0.431 <0.001 0.233 <0.001
Values in parentheses are percentage.
were anastomotic leakage and anastomotic stenosis (both n ¼ 3, 4.0%), and the most common surgical complication in nonoctogenarians was gastric stasis (n ¼ 23, 1.9%). The most common type of medical complication in both groups was pulmonary in nature (pneumonia or pleural effusion). Octogenarians had higher 30-d mortality rates than those of nonoctogenarians (4.0% versus 0.3%, respectively; P ¼ 0.004). All the 30-d mortality patients had medical complications, one acute respiratory distress syndrome, one cerebrovascular accident, and one atrial fibrillation and septic shock. At the median follow-up of 43.7 mo (range, 0.1e97.0 mo), cancer recurred in 194 patients (15.4%) (14 octogenarians [18.7%] and 180 nonoctogenarians [15.2%]; P ¼ 0.415). Nonecancer-related deaths accounted for 29.3% and 7.7% of octogenarian and nonoctogenarian deaths, respectively (P < 0.001). There was no significant difference in cancer-related deaths between the two groups (13.3% versus 12.4%; P ¼ 0.809).
3.3. Survival between octogenarians and nonoctogenarians The overall survival was significantly lower in octogenarians than in nonoctogenarians (P < 0.001) (Fig. 1). However, diseasespecific survival was comparable between the two groups (P ¼ 0.262) (Fig. 2). When adjusted for TNM stage, no statistically significant difference was observed among patients with stage I (P ¼ 0.662) (Fig. 3A), stage II (P ¼ 0.171) (Fig. 3B), stage III (P ¼ 0.165) (Fig. 3C), and stage IV (P ¼ 0.673) (Fig. 3D).
3.4.
Prognostic factors in octogenarians
Univariate and multivariate analyses were performed to detect prognostic factors for octogenarians undergoing curative resection. Univariate analysis revealed that the depth of invasion (T3), lymph node metastasis (positive), and TNM
j o u r n a l o f s u r g i c a l r e s e a r c h 1 9 8 ( 2 0 1 5 ) 8 0 e8 6
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Table 2 e Postoperative morbidities in each group. Nonoctogenarian Octogenarian
Surgical complications Leakage Bleeding Stenosis Intraabdominal abscess A-loop syndrome Gastric stasis Ileus Wound infection Others* Medical complications Pulmonary disease Cardiovascular disease Systemic infections Othersy Total complications
(n ¼ 1187)
(n ¼ 75)
89 (7.5)
12 (16.0)
P value 0.008
19 9 6 2
(1.6) (0.8) (0.5) (0.2)
3 1 3 2
(4.0) (1.3) (4.0) (2.7)
0.138 1.000 0.013 0.019
1 23 20 6 3 30
(0.1) (1.9) (1.7) (0.5) (0.1) (2.5)
0 2 1 0 0 11
(0) (2.7) (1.3) (0) (0) (14.6)
1.000 0.657 1.000 1.000 1.000 <0.001
28 (2.4) 1 (0.1)
8 (10.7) 1 (1.3)
0.001 0.115
0 (0) 1 (0.1) 119 (10.3)
1 (1.3) 1 (1.3) 23 (30.6)
0.059 0.115 <0.001
Values in parentheses are percentages. * Chyle. y Infectious colitis, delirium.
stage (III) significantly affected prognosis in octogenarians (Table 3), whereas multivariate analysis identified only TNM stage (III) as an independent prognostic factor (hazard ratio, 4.096; 95% confidence interval, 1.703e9.851; P ¼ 0.002).
4.
Discussion
The proportion of elderly patients diagnosed with malignancies has been increasing, although the prevalence of
Fig. 1 e Overall survival of octogenarians and nonoctogenarians after curative resection. (Color version of figure is available online.)
Fig. 2 e Disease-specific survival of octogenarians and nonoctogenarians after curative resection. (Color version of figure is available online.)
gastric cancer has approached a plateau or even slightly decreased in recent years [9]. In general, elderly patients have complicated comorbidities and decreased organ reserve; as a result, the postoperative morbidity and mortality rates after gastrectomy with curative intent are higher in elderly than in young patients. Although several recent studies have demonstrated that advances in surgical and anesthetic techniques have reduced perioperative complications and improved short-term surgical outcomes in elderly patients [10e12], many surgeons have some doubts concerning the benefit of curative resection for elderly patients with gastric cancer. Arai et al. [13] evaluated the characteristics of gastric cancer of a large cohort of elderly patients. They found that the relative odds of gastric cancer were higher in men than in women for all age groups, whereas the male-to-female ratio significantly decreased with advancing age, and the early to advanced cancer ratios were approximately equal in all age groups. Other studies have found no significant positive correlation between age and advanced clinical stage in patients with gastric cancer [7,14]. Liang et al. [15] reported that elderly patients were more likely to have more advanced TNM stages and larger tumor sizes. In the present study, octogenarians had a lower male-to-female ratio, deeper invasion, more frequent lymph node metastasis, and more advanced TNM stages. However, these findings cannot simply be interpreted as a correlation between age and advanced stage. Hayashi et al. [16] reported that the rate of diagnosis of gastric cancer in a cancer-screening program was lower in elderly patients (9.1%, aged 65 y) than in nonelderly patients (15.6%, aged <65 y). They also found that nongastric cancer-specific symptoms such as anorexia, dizziness, nausea, fatigue, and weight loss were more frequent in elderly patients than in nonelderly patients. Thus, a delayed diagnosis of gastric cancer is assumed to be a possible cause of the higher TNM stages seen in elderly patients. Greater efforts to establish cancer-screening programs in elderly patients, including
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Fig. 3 e Disease-specific survival of each age group according to TNM stage: (A) stage I, (B) stage II, (C) stage III, and (D) stage IV. (Color version of figure is available online.)
octogenarians, would help lower their stage of gastric cancer at diagnosis, leading to a survival benefit. With respect to surgical treatment, curative resection with adequate lymph node dissection is the most important factor for long-term survival in patients with gastric cancer [16]. In the present study, octogenarians were more likely to have shorter operation times and fewer retrieved lymph nodes than nonoctogenarians, although there was no significant difference in either the curative resection rate (89.3% versus 91.9%, respectively) or the D1/D2 dissection ratio (30.7%:69.3% versus 28.7%:71.3%, respectively). These results are comparable with those of other studies, in which the curative resection rates ranged from 52%e77% in patients aged 80 y [17e19]. However, the survival benefit of D2 lymph node dissection for elderly patients with gastric cancer remains unproven in consideration of postoperative complications and life expectancy. Respiratory and immunologic functions tend to decrease with advancing age, resulting in a higher risk of postoperative complications, such as pneumonia and systemic infections [20]. Although some previous studies found no differences in postoperative morbidity and mortality rates between elderly and nonelderly patients [21e23], others
reported significantly higher rates in elderly patients because of preexisting comorbidities or unrecognized frailty [6,16]. Frailty represents a state of increased vulnerability to stressors, leading to a heightened risk of adverse outcomes. The exhibition of frailty in the elderly population could partly explain their increased morbidity and 30-d mortality. In the present study, octogenarians had longer hospital stays and higher postoperative morbidity and mortality rates than those of nonoctogenarians. Hence, more attention should be given to the treatment of other comorbid diseases to improve the outcome of gastric cancer in octogenarians. Many studies that analyzed the surgical outcomes of elderly patients with gastric cancer found that depth of invasion, lymph node metastasis, and distant metastasis were independent prognostic factors [15,21,24]. Pisanu et al. [10] demonstrated that tumor stage was the only prognostic factor influencing survival for patients aged 75 y. Our results are consistent with these reports and showed that TNM stage was an independent prognostic factor for octogenarians. Survival has also been investigated in many previous studies. Most reported that although the overall survival of elderly patients was significantly lower than that of nonelderly patients, there
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Table 3 e Univariate and multivariate analyses of prognostic factors for octogenarians undergoing gastrectomy. Characteristics
Univariate analysis 3-y Overall survival
Sex Male Female Eastern cooperative oncology group 0 1 No. of comorbidities 0 1 2 Type of operation Subtotal gastrectomy Total gastrectomy Depth of invasion pT1/pT2 pT3/pT4 Lymph node metastasis Negative Positive TNM stage I/II III/IV Lymph node dissection D1þ D2 Complications No Yes
5-y Overall survival
P value
Hazard ratio (95% confidence interval)
P value
51.5 62.3
33.8 53.4
0.312
60.8 24.0
43.4 24.0
0.176
1.997 (0.673e5.926)
0.212
56.9 68.3 37.0
32.0 68.3 0.2
0.199
1.547 (0.634e3.779)
0.338
66.2 48.7
19.0 48.7
0.959
38.7 34.1
38.7 11.7
<0.001
4.096 (1.703e9.851)
0.074
59.5 20.9
59.5 0
0.002
75.0 66.7
23.3 0
<0.001
4.096 (1.703e9.851)
0.002
60.1 57.8
60.1 34.0
0.390
59.4 49.6
40.2 49.6
0.190
2.096 (0.814e5.402)
0.125
was no difference in the disease-specific survival. In particular, because octogenarians had more advanced TNM stages than did nonoctogenarians in the present study, we also analyzed survival according to TNM stage to prevent bias related to stage-related mortality. We found no differences in survival at each stage between octogenarians and nonoctogenarians. According to Mita et al. [21], these results suggest that elderly patients undergoing curative resection for gastric cancer have the same chance of survival as do nonelderly patients. Additionally, the TNM stage of octogenarians was significantly higher; thus, a greater effort toward early detection of cancer can lead to the need for less aggressive surgery and better surgical outcomes. There are some limitations of this study. First, there may have been bias in the patient selection, because our data were obtained retrospectively from a single institution. Regional or population distribution differences also cannot be disregarded. Second, we did not analyze the survival of octogenarians according to the extent of lymph node dissection; therefore, the most appropriate extent of surgery with curative intent remains unclear. Additional well-designed, large cohort studies are needed to clarify this issue.
5.
Multivariate analysis
Conclusions
Octogenarians had higher postoperative morbidity and mortality rates but their cancer-specific survival was comparable
with that of nonoctogenarians. The only independent prognostic factor was TNM stage; neither performance scale nor comorbidities had an impact on prognosis. There is a need to pay more attention to early detection because equivalent long-term survival is achievable in the selected octogenarians. Careful patient selection is also important in those with advanced stage.
Acknowledgment Author contributions: K.H.J., J.H.K., and H.M.C. designed the research; J.H.K., K.H.J. performed the research; K.H.J. and H.M.C. analyzed the data; and K.H.J. and J.H.K. wrote the manuscript.
Disclosure The authors declare that there are no conflicts of interest.
references
[1] Crew KD, Neugut AI. Epidemiology of gastric cancer. World J Gastroenterol 2006;12:354.
86
j o u r n a l o f s u r g i c a l r e s e a r c h 1 9 8 ( 2 0 1 5 ) 8 0 e8 6
[2] Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2010 (ver. 3). Gastric Cancer 2011;14: 113. [3] Degiuli M, Sasako M, Ponti A. Morbidity and mortality in the Italian Gastric Cancer Study Group randomized clinical trial of D1 versus D2 resection for gastric cancer. Br J Surg 2010;97: 643. [4] Dudeja V, Habermann EB, Zhong W, et al. Guideline recommended gastric cancer care in the elderly: insights into the applicability of cancer trials to real world. Ann Surg Oncol 2011;18:26. [5] Bittner R, Butters M, Ulrich M, Uppenbrink S, Beger HG. Total gastrectomy. Updated operative mortality and long-term survival with particular reference to patients older than 70 years of age. Ann Surg 1996;224:37. [6] Eguchi T, Takahashi Y, Ikarashi M, Kasahara M, Fujii M. Is extended lymph node dissection necessary for gastric cancer in elderly patients? Eur J Surg 2000;166:949. [7] Takeshita H, Ichikawa D, Komatsu S, et al. Surgical outcomes of gastrectomy for elderly patients with gastric cancer. World J Surg 2013;37:2891. [8] Washington K. 7th Edition of the AJCC cancer staging manual: stomach. Ann Surg Oncol 2010;17:3077. [9] Bray F, Jemal A, Grey N, Ferlay J, Forman D. Global cancer transitions according to the Human Development Index (2008-2030): a population-based study. Lancet Oncol 2012;13: 790. [10] Pisanu A, Montisci A, Piu S, Uccheddu A. Curative surgery for gastric cancer in the elderly: treatment decisions, surgical morbidity, mortality, prognosis and quality of life. Tumori 2007;93:478. [11] Fujiwara S, Noguchi T, Harada K, Noguchi T, Wada S, Moriyama H. How should we treat gastric cancer in the very elderly? Hepatogastroenterology 2012;59:620. [12] Dittmar Y, Rauchfuss F, Gotz M, Scheuerlein H, Jandt K, Settmacher U. Impact of clinical and pathohistological
[13]
[14]
[15]
[16]
[17] [18]
[19]
[20] [21]
[22]
[23]
[24]
characteristics on the incidence of recurrence and survival in elderly patients with gastric cancer. World J Surg 2012;36:338. Arai T, Esaki Y, Inoshita N, et al. Pathologic characteristics of gastric cancer in the elderly: a retrospective study of 994 surgical patients. Gastric Cancer 2004;7:154. Holmes FF, Hearne E 3rd. Cancer stage-to-age relationship: implications for cancer screening in the elderly. J Am Geriatr Soc 1981;29:55. Liang YX, Deng JY, Guo HH, et al. Characteristics and prognosis of gastric cancer in patients aged 70 years. World J Gastroenterol 2013;19:6568. Hayashi T, Yoshikawa T, Aoyama T, Ogata T, Cho H, Tsuburaya A. Severity of complications after gastrectomy in elderly patients with gastric cancer. World J Surg 2012;36: 2139. Eguchi T, Fujii M, Takayama T. Mortality for gastric cancer in elderly patients. J Surg Oncol 2003;84:132. Kitamura K, Sugimachi K, Saku M. Evaluation of surgical treatment for patients with gastric cancer who are over 80 years of age. Hepatogastroenterology 1999;46:2074. Hanazaki K, Wakabayashi M, Sodeyama H, et al. Surgery for gastric cancer in patients older than 80 years of age. Hepatogastroenterology 1998;45:268. Vallejo AN. Immunological hurdles of ageing: indispensable research of the human model. Ageing Res Rev 2011;10:315. Mita K, Ito H, Hashimoto M, et al. Postoperative complications and survival after gastric cancer surgery in patients older than 80 years of age. J Gastrointest Surg 2013;17:2067. Orsenigo E, Tomajer V, Palo SD, et al. Impact of age on postoperative outcomes in 1118 gastric cancer patients undergoing surgical treatment. Gastric Cancer 2007;10:39. Saidi RF, Bell JL, Dudrick PS. Surgical resection for gastric cancer in elderly patients: is there a difference in outcome? J Surg Res 2004;118:15. Yokota T, Kunii Y, Saito T, et al. Prognostic factors for gastric cancer in the elderly. Eur J Surg Oncol 2001;27:451.