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Can we recommend surgical treatment to the octogenarian with periampullary cancer?: National database analysis in South Korea

  • Chang M. Kang
    Affiliations
    Division of HBP Surgery, Department of Surgery, Yonsei University College of Medicine, South Korea

    Pancreatobiliary Cancer Center, Yonsei Cancer Center, Severance Hospital, Seoul, South Korea
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  • Jin H. Lee
    Affiliations
    Department of Surgery, National Health Insurance Service Ilsan Hospital, Goyang, South Korea
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  • Jung K. Choi
    Affiliations
    Department of Policy Research Affairs, National Health Insurance Service Ilsan Hospital, South Korea
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  • Ho K. Hwang
    Affiliations
    Division of HBP Surgery, Department of Surgery, Yonsei University College of Medicine, South Korea

    Pancreatobiliary Cancer Center, Yonsei Cancer Center, Severance Hospital, Seoul, South Korea
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  • Jae U. Chung
    Affiliations
    Department of Surgery, National Health Insurance Service Ilsan Hospital, Goyang, South Korea
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  • Woo J. Lee
    Affiliations
    Division of HBP Surgery, Department of Surgery, Yonsei University College of Medicine, South Korea

    Pancreatobiliary Cancer Center, Yonsei Cancer Center, Severance Hospital, Seoul, South Korea
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  • Kuk H. Kwon
    Correspondence
    Corresponding author: Department of Surgery, National Health Insurance Service Ilsan Hospital, Goyang, 100, Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, South Korea. Fax: +82 31 900-0138
    Affiliations
    Department of Surgery, National Health Insurance Service Ilsan Hospital, Goyang, South Korea
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Open AccessPublished:December 17, 2020DOI:https://doi.org/10.1016/j.ejca.2020.10.039

      Highlights

      • The number of patients with periampullary cancer is increasing.
      • Surgical survival rates of patients with resectable periampullary cancer are increasing.
      • Even in the elderly, surgical survival rates of periampullary cancer are increasing.
      • The survival rates of octogenarians will be helpful in determining treatment plan.

      Abstract

      Background

      The incidence of periampullary cancer in the elderly is increasing. Safety and oncologic effectiveness of pancreaticoduodenectomy in elderly patients is still controversial.

      Materials and methods

      From 2002 to 2016, patients with periampullary cancer were evaluated. Customised health information data provided by the National Health Insurance Corporation (NHIS-2018-1-157) were used for analysis. Chronological changes in the incidence of periampullary cancer and long-term survival outcomes were estimated according to patients' age.

      Result

      A total of 148,080 patients were found to have periampullary cancer. Chronologically, the incidence of periampullary cancer increased, and the proportion of elderly patients with periampullary cancer prominently increased (about 2.1 times in patients in their 70s and about 4.7 times in those older than 80 years). The number of patients with pylorus-preserving pancreaticoduodenectomy in their 70s (about 5.6 times, p < 0.001) and over 80 years of age (about 8.9 times, p < 0.001) was much higher than the number of patients aged younger than 50 years (about 1.7 times) and in their 60s (about 2.5 times). Long-term survival was different as per diagnosis (p < 0.001). In addition, it was observed that age was a factor attenuating the survival of patients with resected periampullary cancers (p < 0.001). However, in case of patients older than 80 years, those who underwent surgical treatment showed a higher survival rate than those who did not undergo surgical treatment.

      Conclusion

      We can recommend surgical treatment for elderly patients with resectable periampullary cancer. The survival data in this study can be useful references especially in making treatment plan for octogenarians diagnosed with periampullary cancer.

      Keywords

      1. Introduction

      Owing to the low birth rate and ageing of the Korean population in recent years, the working-age population (15–64 years old) has been decreasing for the first time. As per the Korean national statistics [

      http://www.google.co.kr/url?sa=t&rct=j&q=&esrc=s&source=web&cd=14&cad=rja&uact=8&ved=2ahUKEwiqqtuqz-HjAhXBaN4KHaRTCcMQFjANegQIAxAB&url=http%3A%2F%2Fwww.uriminzokkiri.com%2Findex.php%3Fptype%3Digisa1%26no% PaPitWaK. 2015, Statistics Korea.

      ], it was reported in 2000 that Korea entered the ‘ageing society’, in which elderly people older than 65 years account for more than 7% of the total population. Now, Korea is considered an ‘aged’ society, with people older than 65 years comprising more than 14% of the total population in 2019. Korea will soon have a superaged society (highly expected in 2026), wherein the elderly would comprise more than 20% of the total population.
      Compared with other malignancies, periampullary cancers such as pancreatic head cancer, distal bile duct cancer, duodenal cancer and ampulla of Vater cancer tend to be found later in life. The median age at diagnosis is known to be around 70 years [
      • Kamarajah S.K.
      Pancreaticoduodenectomy for periampullary tumours: a review article based on Surveillance, End Results and Epidemiology (SEER) database.
      ]. Pancreaticoduodenectomy (PD) is known to be the essential cure for these tumours. In the past, there was a huge controversy about the role of PD in the management of periampullary cancer owing to high postoperative mortality and morbidity [
      • Whipple A.O.
      Pancreaticoduodenectomy for islet carcinoma : a five-year follow-up.
      ]. With improving surgical technique and advancement of perioperative management, PD is now regarded as a safe and standard approach for management of periampullary cancer [
      • Cameron J.L.
      • Riall T.S.
      • Coleman J.
      • Belcher K.A.
      One thousand consecutive pancreaticoduodenectomies.
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      • Cameron J.L.
      • He J.
      Two thousand consecutive pancreaticoduodenectomies.
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      • He J.
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      • Makary M.A.
      • Cameron J.L.
      • Eckhauser F.E.
      • Choti M.A.
      • et al.
      2564 resected periampullary adenocarcinomas at a single institution: trends over three decades.
      ,
      • Kimura W.
      • Miyata H.
      • Gotoh M.
      • Hirai I.
      • Kenjo A.
      • Kitagawa Y.
      • et al.
      A pancreaticoduodenectomy risk model derived from 8575 cases from a national single-race population (Japanese) using a web-based data entry system: the 30-day and in-hospital mortality rates for pancreaticoduodenectomy.
      ]. In this study, it is not known whether (neo)adjuvant chemotherapy affected patients' survival or not, so it is not known how (neo-) adjuvant chemotherapy affected patients' survival. However, although this study is in a state wherein it is not known whether (neo-) adjuvant chemotherapy affected patients' survival or not, it is worth because it is a study that can determine how surgical treatment can affect survival in elderly patients older than 80 years.
      On the other side, the decision to perform PD in elderly patients with resectable periampullary cancer is not easy. Although PD is considered a safe surgical procedure, its postoperative morbidity is still high, up to 47% [
      • Ahmad S.A.
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      • Maithel S.K.
      • et al.
      Factors influencing readmission after pancreaticoduodenectomy: a multi-institutional study of 1302 patients.
      ,
      • Winter J.M.
      • Cameron J.L.
      • Campbell K.A.
      • Arnold M.A.
      • Chang D.C.
      • Coleman J.
      • et al.
      1423 pancreaticoduodenectomies for pancreatic cancer: a single-institution experience.
      ,
      • Schmidt C.M.
      • Powell E.S.
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      • Howard T.J.
      • Wiebke E.A.
      • Wiesenauer C.A.
      • et al.
      Pancreaticoduodenectomy: a 20-year experience in 516 patients.
      ,
      • Grobmyer S.R.
      • Pieracci F.M.
      • Allen P.J.
      • Brennan M.F.
      • Jaques D.P.
      Defining morbidity after pancreaticoduodenectomy: use of a prospective complication grading system.
      ], and mortality cannot be overlooked, as it can be 0–8.8% [
      • Cameron J.L.
      • He J.
      Two thousand consecutive pancreaticoduodenectomies.
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      • Are C.
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      • Smith L.
      Preoperative nomogram to predict risk of perioperative mortality following pancreatic resections for malignancy.
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      • et al.
      Hospital volume and patient outcomes in hepato-pancreatico-biliary surgery: is assessing differences in mortality enough?.
      ,
      • Simons J.P.
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      • Tseng J.F.
      National complication rates after pancreatectomy: beyond mere mortality.
      ,
      • Spizzo G.
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      • et al.
      Methylation status of the Ep-CAM promoter region in human breast cancer cell lines and breast cancer tissue.
      ,
      • Trede M.
      • Schwall G.
      • Saeger H.D.
      Survival after pancreatoduodenectomy. 118 consecutive resections without an operative mortality.
      ]. In addition, long-term cancer-specific survival after curative PD for periampullary cancer varies as per the origin of the cancer, ranging at around 20% in pancreatic head cancer and 50% in ampulla of Vater cancer [
      • Kamarajah S.K.
      Pancreaticoduodenectomy for periampullary tumours: a review article based on Surveillance, End Results and Epidemiology (SEER) database.
      ,
      • Poultsides G.A.
      • Huang L.C.
      • Cameron J.L.
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      • et al.
      Duodenal adenocarcinoma: clinicopathologic analysis and implications for treatment.
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      Treatment and survival in 13,560 patients with pancreatic cancer, and incidence of the disease, in the West Midlands: an epidemiological study.
      ,
      • Neoptolemos J.P.
      • Russell R.C.
      • Bramhall S.
      • Theis B.
      Low mortality following resection for pancreatic and periampullary tumours in 1026 patients: UK survey of specialist pancreatic units. UK Pancreatic Cancer Group.
      ].
      Therefore, the decision-making process to perform PD should be balanced and consider life expectancy, comorbidity potentially related to postoperative mortality and cancer aggressiveness influencing long-term oncologic outcomes. There are several articles reporting oncologic safety of PD for periampullary cancer in elderly patients [
      • Futagawa Y.
      • Kanehira M.
      • Furukawa K.
      • Kitamura H.
      • Yoshida S.
      • Usuba T.
      • et al.
      Study on the validity of pancreaticoduodenectomy in the elderly.
      ,
      • Oguro S.
      • Shimada K.
      • Kishi Y.
      • Nara S.
      • Esaki M.
      • Kosuge T.
      Perioperative and long-term outcomes after pancreaticoduodenectomy in elderly patients 80 years of age and older.
      ,
      • El Nakeeb A.
      • Atef E.
      • El Hanafy E.
      • Salem A.
      • Askar W.
      • Ezzat H.
      • et al.
      Outcomes of pancreaticoduodenectomy in elderly patients.
      ,
      • Kow A.W.
      • Sadayan N.A.
      • Ernest A.
      • Wang B.
      • Chan C.Y.
      • Ho C.K.
      • et al.
      Is pancreaticoduodenectomy justified in elderly patients? The surgeon.
      ,
      • Beltrame V.
      • Gruppo M.
      • Pastorelli D.
      • Pedrazzoli S.
      • Merigliano S.
      • Sperti C.
      Outcome of pancreaticoduodenectomy in octogenarians: single institution's experience and review of the literature.
      ], but only a few specialised centres are involved, and the size of the study population is very limited for drawing a conclusion.
      Big data involves extraction of values from data, including unstructured data sets that are not available from the usual types of databases [
      • Househ M.S.
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      • Ruping S.
      [Big data in medicine and healthcare].
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      • Mayer-Schonberger V.
      [Big data: a revolution that will transform our lives].
      ]. By analysing big data, it is possible to produce a scientific basis for decision-making, which is considered a part of evidence-based approach.
      The purpose of this study was to investigate the trend of care for patients with periampullary cancer in Korea based on the national medical big data of patients with periampullary cancer who underwent PD and to describe the oncologic outcomes after PD according to patients' age. It is expected that this study could provide elderly patients, their family members and surgeons with additional important information required for decision-making with regard to the treatment strategy for resectable periampullary cancer.

      2. Materials and methods

      2.1 Data and study population

      The data used for analysis were the “customised health information data” provided by the National Health Insurance Corporation (NHIS-2018-1-157). Study subjects were patients who were diagnosed with cancer between 2002 and 2016 and hospitalised more than once. As per the 10th version of the International Classification of Diseases (ICD-10), the diagnostic codes for periampullary cancer were C17, C24 and C25. The Institutional Review Board (IRB) of the National Health Insurance Medical Center (NHIMC) approved all components and procedures of this study (IRB file no. NHIMC 2018-02-010).

      2.2 Study variables

      Age refers to age at the time of cancer diagnosis, and it was divided into four categories: ≤59 years, 60s, 70s and ≥80 years. More subdivided, among the diagnostic code for periampullary cancer as per the ICD-10 classification, the disease groups used in this study are as follows: Duodenal cancer (DUO), distal bile duct cancer (BD), ampulla of Vater cancer (AOV) and pancreatic head cancer (PHC) were defined as cases with main diagnosis codes C17.0, C24.0, C24.1 and C25.0, respectively. In addition, among the patients diagnosed with periampullary cancer, patients other than those diagnosed as C17.0, C24.0, C24.1 and C25.0 were classified as ‘‘the others’. The Electronic Data Interchange procedure codes for patients who have undergone Whipple operation and pylorus-preserving pancreaticoduodenectomy (PPPD) are Q7571 and Q7572, respectively.

      2.3 Statistics

      Incidence rate calculates a newly detected patient in the year concerned. An incident case was defined as a person newly diagnosed or operated for periampullary cancer in the corresponding year, and incidence was defined as the number of incident cases in the corresponding year per 100,000 using the resident registration population on 1st July each year. Age, diagnosis and operation-specific incidence were calculated by dividing the number of cases in specific groups by the corresponding specific population and expressed as cases per 100,000. Tests of linear trends in incidence rates were conducted using ordinal scaling across categories. The trend for incidence of periampullary cancer was ascertained using the Cochran-Armitage trend test. The Kaplan-Meier survival curve method was used to determine the probability of survival among groups, and the differences were compared with log-rank statistics. In this study, data related to comorbidity were analysed using the Charlson Comorbidity Index (CCI). Statistical analysis was performed using SAS, version 9.4. P-value <.05 was considered to be significant.

      3. Results

      3.1 General characteristics of patients with periampullary cancer in South Korea

      From January 2002 to December 2016, it was found that a total of 148,080 patients had periampullary cancer. Among them, 83,685 were men (56.5%) and 64,395 (43.5%) were women, with the mean calculated age of 67.5 ± 12.4 years.
      It was noted that the incidence of periampullary cancer increased chronologically. In 2002, 8242 patients were found to have periampullary cancers, but in 2016, 13,235 patients were diagnosed with periampullary cancer, which has steadily increased over the past 15 years (p < 0.001), leading to a number that is approximately 1.6 times higher than the number in 2002. Among them, it was estimated that BD (about 1.98 times, p < 0.001), PHC (about 1.3 times, p = 0.0044) and ‘others’ (not specified, about 1.6 times, p < 0.001) were observed to have significantly increased during the study period (Fig. 1).
      Fig. 1
      Fig. 1Incidence of periampullary cancer in South Korea (incidence per 100,000 population). AOV: ampulla of Vater cancer, DUO: duodenal cancer, BD: distal bile duct cancer, NS: not specified, PH: pancreatic head cancer.
      From the perspective of patients' age, it was noted that the incidence of periampullary cancer in patients older than 70 years (p < 0.001) and older than 80 years (p < 0.001) increased with statistical significance (Fig. 2). In 2002, 2031 patients were in their 70s, and 625 patients were older than 80 years. However, in 2016, 4289 patients were in their 70s (about 2.1 times), and 2936 were older than 80 years (about 4.7 times), respectively, suggesting that age was one of the factors associated with an increase in the number of cases of periampullary cancer in Korea.
      Fig. 2
      Fig. 2Incidence of periampullary cancer based on patients' age (incidence per 100,000 population).

      3.2 General characteristics of periampullary cancer resection in South Korea

      A total of 22,340 patients (15.1%) had undergone resection of periampullary cancer. Overall, the number of patients with resected periampullary cancers also increased during the study period (p < 0.001). It was observed that the number of PPPD procedures significantly increased (p < 0.001), while the number of Whipple operations remained steady (p < 0.001) in Korea (Fig. 3).
      Fig. 3
      Fig. 3Number of pancreaticoduodenectomies performed for periampullary cancer (incidence per 100,000 population).
      It was noted that the number of patients who underwent resection of periampullary cancer generally increased as per age. In particular, it was found that the number of patients in their 70s (about 5.6 times, p < 0.001) and older than 80 years (about 8.9 times, p < 0.001) was much higher than the number of patients aged younger than 50 years (about 1.7 times) and in their 60s (about 2.5 times) (Fig. 4).
      Fig. 4
      Fig. 4Number of resected periampullary cancers as per patients' age calculated annually (incidence per 100,000 population).

      3.3 Long-term oncological outcomes of patients with periampullary cancer after PD as per age

      Overall, it was analysed that patients with resected periampullary cancers showed significantly superior survival outcomes over those with unresected periampullary cancer (median, .59 years [95% confidence interval: .58–.60] vs. median, 3.25 years [95% confidence interval: 3.14–3.36], p < 0.0001).
      In addition, there were also significant survival differences as per patients' age. Age was a factor attenuating the survival of patients with resected periampullary cancer (p < 0.001, Fig. 5).
      Fig. 5
      Fig. 5Impact of age on long-term survival outcomes in resected periampullary cancer.
      This observation could also be confirmed in individualised resected periampullary cancers, such as DUO (Fig. 6a, p < 0.0001), BD (Fig. 6b, p < 0.0001), AOV (Fig. 6c, p < 0.0001) and PHC (Fig. 6b, p < 0.0001).
      Fig. 6
      Fig. 6Impact of age on long-term survival outcomes in resected individualised periampullary cancer. Long-term survival probability: duodenal cancer (a), bile duct cancer (b), ampulla of Vater cancer (c) and pancreatic head cancer (d).

      3.4 Counselling for decision-making of surgical resection in octogenarians with periampullary cancer

      Table 1 summarises short-term and long-term survival probabilities after the resection of periampullary cancer in patients older than 80 years. The present data will be useful during counselling for patients and family members when considering the surgical approach for patients older than 80 years. It was estimated that the overall postoperative 30-day, 90-day, 1-year-, 3-year and 5-year survival probabilities were 98.7%, 90.8%, 69.7%, 44.7% and 36.8%, respectively, which showed statistically significant superior outcomes compared with unresected, individual periampullary cancer (p < 0.001). The 5-year survival probability of AOV was found to be 53.7%, which was the highest, followed by DUO (51.4%), BD (40.3%) and PHC (34.4%). On the contrary, 1-year overall survival probability of patients with unresected periampullary cancer was noted to be 21.5% (range, 15.2–46.8%).
      Table 1Summary of short-term and long-term survival probabilities of patients older than 80 years as per individual resected periampullary cancer.
      Survival probabilityCancer origin (%)
      AOV (1259)DUO (598)BD (5832)PHC (3766)Overall (11,455)
      UR (1110)R (149)UR (563)R (35)UR (5589)R (243)UR (3583)R (183)UR (10,845)R (610)
      30-day90.99836.397.184.995.983.198.985.097.4
      90-day77.194.659.185.764.790.554.196.262.293.0
      1-year46.880.528.171.431.874.515.263.427.772.5
      3-year26.858.418.551.417.444.48.937.215.646.1
      5-year22.753.714.751.415.840.38.334.414.042.5
      UR, unresected; R, resected; AOV, ampulla of Vater cancer; DUO, duodenal cancer; BD, distal bile duct cancer; PHC, pancreatic head cancer.
      Table 2 shows the difference in the prevalence of hypertension (HTN) and diabetes, and the difference in CCI values, depending on whether or not PD was performed among patients older than 80 years. It showed that the prevalence of HTN, diabetes mellitus and the value of CCI was higher in the group that underwent surgery. In addition, survival rate was higher in patients with resected periampullary cancer. Moreover, in the patients who underwent surgery, the number of male patients was higher than that of female patients. In addition, among the patients who underwent surgery, patients with BD were the most common, followed by patients with PHC, patients with DUO and patients with AOV.
      Table 2Among patients diagnosed with periampullary cancer, comparison of survival rates based on sex, comorbidity and cancer origin of patients older than 80 years.
      Comparative analysis factorTotal Patients NumberWhether and how to perform SurgeryP-value
      Un-resectedResected
      24,318(n)100(%)23,632(n)97.2(%)686(n)2.8(%)
      SexMale995640.9959540.636152.6<.0001
      Female14,36259.114,03759.432547.4
      HTNNo13,15054.112,85054.430043.7<.0001
      Yes11,16845.910,78245.638656.3
      DMNo19,13678.718,66479.047268.8<.0001
      Yes518221.3496821.021431.2
      CCI0345114.2338714.3649.3<.0001
      1684528.1668528.316023.3
      ≥214,02257.713,56057.446767.4
      DiagnosisDUO (C17)5982.55632.4355.1<.0001
      BD (C24.0)583324.0558923.724335.4
      AOV (C24.1)12585.211104.714921.7
      PHC (C25.0)376615.5358315.218326.7
      The others12,86352.912,78754.17611.1
      SurvivalSurvival311312.8284512.026839.1<.0001
      Death21,20587.220,78788.041860.9
      AOV, ampulla of Vater cancer; BD, distal bile duct cancer; CCI, Charlson Comorbidity Index; DM, diabetes mellitus; DUO, duodenal cancer; HTN, hypertension; PHC, pancreatic head cancer.

      4. Discussion

      The reason for an overall rise in the ageing of the world's population is the continued decline in fertility rates and increased life expectancy owing to improved general hygiene, economic status, nutritional support, infection control, lifestyle modification and medical care [
      • Mathers C.D.
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      ]. This demographic change has resulted in increasing numbers and proportions of people older than 60 years, especially the age group of more than 80 years [
      • Riall T.S.
      What is the effect of age on pancreatic resection?.
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      • Belyaev O.
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      ]. It was estimated that the proportion of the world population older than 65 years is expected to increase from 8.2% in 2015 to 17.6% in 2060, and the percentage of Koreans older than 65 years will increase from 13.1% in 2015 to 40.1% in 2060 [

      http://www.google.co.kr/url?sa=t&rct=j&q=&esrc=s&source=web&cd=14&cad=rja&uact=8&ved=2ahUKEwiqqtuqz-HjAhXBaN4KHaRTCcMQFjANegQIAxAB&url=http%3A%2F%2Fwww.uriminzokkiri.com%2Findex.php%3Fptype%3Digisa1%26no% PaPitWaK. 2015, Statistics Korea.

      ]. In fact, in the early 1970s, the average lifespan of Korean people was 62.7 years. However, it was recently reported that the average expected lifespan of Korean people was estimated to be 82.4 years, which is an increase of 19.8 years (31.6%), ranking South Korea as one of the highest among Organization for Economic Cooperation and Development; OECD countries [].
      From the viewpoint of pancreatic surgery, this global ageing process expected to provoke various social dilemmas, such as whether to actively treat or not treat octogenarians with periampullary cancer as periampullary cancers are known to occur later in life; the median age at diagnosis is reported to be about 70 years. In fact, the current Korean national big data shows that the number of patients with periampullary cancer older than 70 years is significantly increasing, and the change in the number of patients aged 80 years and older was most significant (increased by about 2.1 times in patients in their 70s and by about 4.7 times for those in their 80s). The resection rate also dramatically increased, especially in the elderly population (70s, increased by about 5.6 times, p < 0.001; and 80s, by about 8.9 times, p < 0.001).
      Increasing age itself can be a significant surgery-related risk factor owing to limited physiological reserves and coexisting medical conditions that can potentially affect postoperative surgical outcomes. Turrentine et al. [
      • Turrentine F.E.
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      ] investigated the risk factors, morbidity and mortality in elderly patients based on the American College of Surgeons National Surgical Quality Improvement Program database, including a total of 7696 surgical procedures. They showed that patients older than 80 years had a morbidity of 51% and mortality of 7% and that postoperative morbidity and mortality increased progressively with increasing age (p < 0.001). Although PD is regarded as the safe golden standard surgical approach, potential morbidity is still high, and surgery-related mortality cannot be overlooked [
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      ], especially in octogenarians. Therefore, the current situation can be challenging for pancreatic surgeons. Balance between surgical risk, physiological reserve to handle PD-related surgical stress and natural life expectancy should be considered when planning the management strategy.
      We previously published our institutional experiences of radical surgery for periampullary cancer in elderly patients. Kang et al. [
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      • Choi G.H.
      • Kim K.S.
      • Choi J.S.
      • Lee W.J.
      • et al.
      Pancreaticoduodenectomy of pancreatic ductal adenocarcinoma in the elderly.
      ] reported on 11 patients older than 70 years (mean age, 73.4 ± 2.4 years) who underwent PD for pancreatic cancer, showing frequent postoperative complications (p = 0.049), prolonged length of hospital stay compared with younger patients (p = 0.012), and similar long-term survival outcomes (p > 0.05). Kim et al. [
      • Kim S.H.
      • Chong J.U.
      • Lim J.H.
      • Chung M.J.
      • Park J.Y.
      • Bang S.M.
      • et al.
      Oncologic outcomes after radical surgery for periampullary cancer in octogenarians.
      ] recently analysed 25 patients older than 80 years who underwent PD. It observed that 20% of the patients had major postoperative complications, but no mortality was noted. The group of patients who underwent radical surgery was found to show long-term oncological benefits compared with the non-surgery group (7.6 months vs. 29.3 months, respectively, p < 0.001). However, when reviewing the literature reporting short-term and long-term oncological outcomes of PD in elderly patients, the efficacy of PD for elderly patients with periampullary cancer remains controversial.
      Beltrame et al. [
      • Beltrame V.
      • Gruppo M.
      • Pastorelli D.
      • Pedrazzoli S.
      • Merigliano S.
      • Sperti C.
      Outcome of pancreaticoduodenectomy in octogenarians: single institution's experience and review of the literature.
      ] published their institutional experiences of PD in octogenarians with a review of 14 literature works reporting pancreatic resection in patients aged 80 years and older. It was found that both short-term postoperative outcomes, such as rate of complications (40% vs. 43%) and mortality rate (4% vs. 0%), and long-term survival rates (21 months vs. 19 months) were not statistically significant. In addition, the literature review also showed that surgical outcomes after pancreatectomy were not different between octogenarians and younger patients.
      On the other hand, Kang et al. [
      • Kang J.S.
      • Kim H.
      • Kim J.R.
      • Han Y.
      • Kim E.
      • Byun Y.
      • et al.
      Short- and long-term outcomes of pancreaticoduodenectomy in elderly patients with periampullary cancer.
      ] reported short- and long-term outcomes of PD in elderly patients (age ≥75 years) with periampullary cancer. They analysed a total of 168 elderly patients (13.5%) among 1249 patients who underwent PD and demonstrated similar short-term postoperative outcomes of elderly patients to those of younger patients. However, when it comes to long-term oncologic outcomes, 5-year overall survival rate (p < 0.001) and 5-year cumulative recurrence rate (p = 0.095) were all lower in elderly patients. Kim et al. [
      • Kim S.Y.
      • Weinberg L.
      • Christophi C.
      • Nikfarjam M.
      The outcomes of pancreaticoduodenectomy in patients aged 80 or older: a systematic review and meta-analysis.
      ] recently reviewed 18 literature works on comparison of postoperative outcomes in patients older than 80 years with those of younger patients who underwent PD. They reported approximately twice the 30-day postoperative mortality and a 50% increase in the complication rate. In addition, they reported that long-term survival outcomes appeared after a shorter period than those in younger patients (median survival time/5-year-survival rate, 10–33 months/19–45% vs. 12–40 months/27–51%), suggesting that careful patient selection and potential long-term oncologic benefits should be considered when planning for PD in this group of patients.
      In clinical practice, it is difficult to counsel elderly patients older than 80 years with resectable periampullary cancers and their families. However, surgical or medical oncologists should determine the treatment strategy based on the current available evidence, based on which surgeons should decide whether to actively treat patients with surgical intervention or treat them passively with conservative management. However, the currently available evidence is mostly based on a limited number of patients, specialised high-volume centres and publications reported more than 10 years ago. In addition, long-term survival data are limited to only about 25% of the literature works reporting long-term survival outcomes (21.4% [
      • Beltrame V.
      • Gruppo M.
      • Pastorelli D.
      • Pedrazzoli S.
      • Merigliano S.
      • Sperti C.
      Outcome of pancreaticoduodenectomy in octogenarians: single institution's experience and review of the literature.
      ] and 27.8% [
      • Kim S.Y.
      • Weinberg L.
      • Christophi C.
      • Nikfarjam M.
      The outcomes of pancreaticoduodenectomy in patients aged 80 or older: a systematic review and meta-analysis.
      ]).
      The question is whether to treat or not to treat octogenarians with periampullary cancer. In this regard, the big data–based approach would be able to generalise the long-term oncologic outcomes of resected periampullary cancer, along with providing reliable references to help surgeons and medical oncologists deciding management plan and family counselling. As per the present study, the patient's age should be considered before resecting periampullary cancer. Age was found to attenuate long-term oncologic outcomes of patients with resected periampullary cancers. The present study also provides information on both short-term surgery-related risks (30-day and 90-day mortality) and long-term survival outcomes (1-year, 3-year and 5-year survival) of age-matched patients with either resectable or unresectable cancers, by which postoperative risk and time-dependent survival probability can be estimated.
      A specific method for application and validation must be further investigated. However, surgeons and medical oncologists can provide basic evidence relating to predicting not only postoperative complication rates and the mortality rates but also long-term oncologic outcomes after the resection of periampullary cancers for octogenarians with periampullary cancer and their families to make proper decisions on their treatment methods. The present study is thought to be a potential clue to answer these questions.
      The present study had several limitations. First, there was no information on the individual stage of cancer and chemotherapy. Second, heterogeneous pathologic entities may have been contaminated in individual periampullary cancer. The 5-year survival of PHC was thought to be the sum of different pathologic cancer diagnoses, such as pancreatic ductal adenocarcinoma, intraductal papillary mucinous neoplasm with cancerous transformation and neuroendocrine carcinoma. Third, also, in this study, it is not known whether (neo)adjuvant chemotherapy affected patients' survival or not, so it is not known how (neo-) adjuvant chemotherapy affected patients' survival. The role of (neo-) adjuvant therapy in patients with periampullary cancer is very important. Therefore, even in elderly patients, it is not known whether or not (neo-) adjuvant therapy can cause differences in survival rates. From this point of view, this study can be said to have significant limitations. However, although this study is in a state wherein it is not known whether (neo-) adjuvant chemotherapy affected patients' survival or not, it is worth because it is a study that can determine how surgical treatment can affect survival in elderly patients older than 80 years. In addition, the exact reasons on why octogenarians could not undergo resection of periampullary cancer were unknown. Was it because the cancers are anatomically unresectable? Alternatively, was it because of patients' refusal to receive active surgical treatment? Unfortunately, big data in this study is not based on the common data model (CDM), and thus, this study did not reflect performance status and patient preferences. However, the differences in survival rates related to comorbidity are summarised in Table 2 and added. When the CDM collects big medical data in future, we will be able to refer more diverse and detailed clinical data including performance status and patient preferences. Nevertheless, our study up to present based on the Korean national big data demonstrates that the incidence of resectable periampullary cancer in octogenarians is increasing, with age having an adverse survival influence on periampullary cancer resection. In addition, the survival graph for each disease (Fig. 6) shows that the survival rate at ages lower than 70 years is clearly dominant in case of patients who underwent surgical treatment. It also shows that in case of patients older than 70 years except for duodenal cancer, patients who underwent surgical treatment showed higher survival rate than patients who did not undergo surgical treatment. In case of patients older than 80 years, as shown in Table 1, Table 2, patients who underwent surgical treatment showed a higher survival rate than those who did not undergo surgical treatment.
      Considering the aforementioned results, we can recommend surgical treatment for elderly patients with resectable periampullary cancer. Thus, the survival data in this study can be useful references especially in the process of making a treatment plan for the octogenarians diagnosed with periampullary cancer. However, further studies are required.

      Funding

      This study was supported by research grant from National Health Insurance Service Ilsan Hospital (HIMC2018-20-004).

      Author contributions

      Chang Moo Kang, Conceptualisation, Methodology, Validation, Formal analysis, Investigation, Writing – original draft, Writing-Review & Editing. Jin Ho Lee, Conceptualisation, Methodology, Validation, Formal analysis, Investigation, Resources, Writing – original draft, Writing-Review & Editing, Visualisation Preparation. Jung Kyu Choi, Validation, Formal analysis, Data curation, Visualisation Preparation. Ho Kyoung Hwang, Validation, Writing-Review & Editing. Jae Uk Chung, Writing-Review & Editing. Woo Jung Lee, Methodology, Writing-Review & Editing. Kuk Hwan Kwon, Conceptualisation, Methodology, Investigation, Supervision, Project administration, Funding acquisition, Writing-Review & Editing. Dr. Chang Moo Kang and Dr. Jin Ho Lee had equal contributions to this manuscript as co-first author.

      Conflict of interest statement

      The authors declare no conflict of interest.

      Acknowledgements

      Research grant from National Health Insurance Service Ilsan Hospital supported this study (HIMC2018-20-004).

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