Long-term outcomes of gastric cancer in a single small center: a retrospective analysis

doi:10.21203/rs.3.rs-22786/v1

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Long-term outcomes of gastric cancer in a single small center: a retrospective analysis

https://doi.org/10.21203/rs.3.rs-22786/v1

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Background

The aim of this study is to evaluate the long-term outcomes and short-term outcomes of gastric cancer patients who underwent surgical treatment in a small-sized single center by one surgeon.

Methods

Results

The mean follow-up period was 78.26 months. The overall survival and relapse-free survival rates of all patients were 84.6%, and 86.5%, respectively; the postoperative morbidity and mortality rates were 12% and 0.36%, respectively. The relapse-free survival rate was higher in period 2 than in period 1 (82.9% versus 90.2%, p = 0.002)

Conclusions

Our study showed that the short-term outcomes and long-term outcomes of gastric cancer treatment in a small-sized hospital were comparable to those in large-sized hospitals. Accumulated individual surgeon volume was related to a high relapse-free survival rate.

Oncology

Cancer Biology

Gastric cancer

Surgeon volume

Long-term outcome

Numerous developments have been made in surgical techniques and adjuvant chemotherapy for gastric cancer. However, gastric cancer remains the fourth most common cause of cancer-related death worldwide (1). Its treatment requires a complex surgical procedure and multidisciplinary treatment, but high mortality and relapse rates are important problems that need to be overcome.

To improve the quality of gastric cancer treatment, studies concerning volume-outcome relationships have been ongoing since 1990. It has been reported that hospital volume has a positive relationship with clinical outcome (2, 3). Based on these studies, Western countries, such as the United States, England, Australia, the Netherlands, and Sweden, started a policy for the centralization of cancer treatment in high-volume centers (4–8).

Surgeon volume is another important factor (9, 10), and there is a controversy over whether hospital volume or surgeon volume is more important. However, there are a limited number of studies concerning the relationship between individual surgeon volume and long-term outcomes of gastric cancer.

The aim of our study is to evaluate the short-term outcomes and long-term outcomes of gastric cancer patients who underwent surgical treatment in a small-sized single center in a local region. Based on our experience, we analyzed the changes in outcomes as the individual surgeon volume accumulated.

Patients

We retrospectively reviewed the medical records of 950 patients who underwent surgical treatment for gastric cancer between January 2000 and January 2010 at Dong-rae Paik Hospital, Inje University College of Medicine, Busan, Korea. Among the 950 patients, we excluded patients who underwent neoadjuvant chemotherapy (n = 2), patients who were diagnosed with stage VI cancer (n = 98), patients who had a postoperative biopsy that revealed a remnant tumor (n = 17), patients who underwent completion gastrectomy due to recurrent gastric cancer (n = 7), patients who were diagnosed with double primary cancer from other organs (n = 3), and patients who died within 50 days after surgery (n = 3). After exclusion, 820 patients over the age of 19 were included in the analysis. The patients’ clinicopathologic characteristics, treatment methods, and treatment outcomes including short-term and long-term outcomes were analyzed (Fig. 1).

Clinical outcomes

For gastric cancer staging, the 7th American Joint Committee on Cancer(AJCC) TNM staging system was used. Other clinicopathologic characteristics were evaluated according to the Japanese classification for gastric cancer (11). Postoperative morbidity was defined by the Clavien-Dindo classification with any grade within 50 days after surgery, and major complications were defined as complications graded higher than grade 3 in Clavien-Dindo classification (12). Postoperative mortality was defined as death from any cause within 50 days after surgery.

Patients with stage Ia cancer did not undergo out postoperative adjuvant chemotherapy. For some stage Ib and stage II patients, oral fluorouracil was administered. Other stage II and most stage III patients received a platinum-based regimen, an MMC combined regimen or oral S-1 chemotherapy.

We followed patients from the operation day to December 31, 2013. All patients’ physical examinations were checked every two months, and chest X-rays, tumor markers, and abdominal computed tomography scans were performed every 6 months. Esophagogastroduodenoscopy was performed every year. If we lost the patients’ to follow-up, we collected data regarding survival or cause of death from the National Statistical Office of Korea. Overall survival was calculated from the date of the operation to the date of cancer-related death or the last follow-up. Disease recurrence was identified by imaging findings or biopsy-proven recurrent gastric cancer.

Since all the surgeries were performed by one individual surgeon, we were able to analyze the changes in long-term outcomes as the individual surgeon volume accumulated. Therefore, we divided the time period into 2 groups: 2000–2005 (period 1, n = 407) and 2006–2010 (period 2, n = 413). Subgroup analysis was performed between the two groups.

The research protocols were approved by the IRB of our institute. (IRB no 19–0189)

Statistical analysis

SPSS version 25 (SPSS, Chicago, IL) was used for statistical analysis. Independent sample t-tests and Mann-Whitney tests were used for continuous variables. A Chi-square test and linear-by-linear association were used to analyze categorical data. The Kaplan-Meier estimator was used to analyze survival curves, while the log-rank test was used to compare the survival distributions (or rates) of corresponding groups. A p-value of less than 0.05 was considered statistically significant for all cases.

Clinicopathologic characteristics

The demographics of the patients and the clinicopathologic characteristics overall and in period 1 (P1) and period 2 (P2) are shown in Table 1. The mean age was 58.8 years, and BMI was 22.7. BMI; BMI was higher in P2 than P1 (22.4 vs 22.9, p = 0.041). There were no changes in tumor location between the two periods. The distribution of T stage was different in both periods (P1 vs P2, T1: T2: T3: T4, 59.8%: 10.4%: 27.2%: 2.7% vs 56.5%: 10.1%: 30.7%: 2.7%, p = 0.042), but the distribution of N stage and the total stage had no significant difference (P1 vs P2, N1: N2: N3, 64.9%: 11.1%: 10.3% vs 68:0%: 9.7%: 8.2%, p = 0.544) (P1 vs P2, stage1: stage2: stage3, 60.4%: 21.9%: 21.9% vs 66.8%: 13.8%: 19.4%, p = 0.117). Histopathologically, less perineural invasion (PNI) and lymphatic invasion(LVI) was detected in P2 than in P1 (P1 vs P2, PNI positive: PNI negative, 3.9%: 96.1% vs 6.6%: 93.4%, p < 0.001) (P1 vs P2, LVI positive: LVI negative, 12.4%: 87.6% vs 17.4%: 82.6%, p < 0.001).

Short-term treatment outcomes

Table 2 shows short-term treatment outcomes of 820 patients, 741 underwent gastrectomy with an open method (90.4%), and 79 underwent laparoscopic-assisted distal gastrectomy (LADG) (9.6%). There was a higher rate of LADG in P2 than in P1 (P1 vs P2, 1.2% vs 17.9%, p < 0.001). There was no difference in the extent of resection in either period (P1 vs P2, subtotal: total: other, 80.7%: 18.9%: 0.4% vs 81.3%: 18.2%: 0.5%, p = 0.743). Three patients underwent other types of gastrectomies: two proximal gastrectomies, and one gastric wedge resection.

The distrubution of lymph node dissection was different in both periods (P1 vs P2, D1: D1+: D2, 4.4%: 44.1%: 51.5% vs 0.5%: 44.5%: 55.0%, p < 0.001). More lymph nodes were harvested in P2 than P1 (27.2 vs 41.4, p < 0.001).

There was a shorter hospital stay in P2 than in P1 (18.0 vs 14.6, p < 0.001). A total of 660 patients underwent postoperative adjuvant chemotherapy either orally or intravascularly (IV) (80.5%). The distribution of adjuvant chemotherapy was different in both periods (P1 vs P2, none: oral: IV, 15.2%: 44.7%: 40.0% vs 23.7%: 63.0%: 13.3%, p < 0.001).

The total postoperative morbidity rate was 11.9%, and the major complication rate was 4.1%. The postoperative morbidity rate was not significantly different between the two periods (P1 vs P2, 12.3% vs 12.0%, p = 0.751). The major complication rate was also not significantly different between the two periods (P1 vs P2, 3.9% vs 4.4%, p = 0.942). Although we did not include mortality in the statistical analysis, 3 cases of mortality were recorded within 50 days after surgery (postoperative mortality rate = 0.36%). The first case was a 68-year-old male, who died of acute myocardial infarction on postoperative day(POD) 17. The second case was a 70-year-old female, who died of spontaneous intracranial hemorrhage on POD 11. The third case was a 72-year-old male, who died of acute respiratory distress syndrome on POD 32.

Long-term treatment outcomes

The mean follow-up period was 78.26 months. The 5-year overall survival rate and relapse-free survival rate of all patients were 84.6% and 86.5%, respectively. The 5-year overall survival rate and relapse-free survival rate for each stage were 97.8% and 97.8% for stage I, 82.6% and 86.2% for stage II, and 43.4% and 49.7% for stage III, respectively (Fig. 2). We identified 111 cases of recurrence among 820 patients. Thirty-one patients experienced liver recurrence (27.9%), 27 had distant lymph nodes (24.3%), 24 had peritoneum recurrence (21.6%), 16 had bone recurrence (14.4%), and 29 had local recurrence (26.1%). Forty-one patients (36.9%) had multiple metastases in at least two different organs.

The relapse-free survival rate was higher in P2 than in P1 (P1 vs P2, 82.9% vs 90.2%, p = 0.002). The overall survival rate was higher in P2 than in P1, but there was no significant difference (P1 vs P2, 78.1% vs 80.3%, p = 0.713) (Fig. 3).

Multivariate analysis

In multivariate analysis, the independent factors affecting overall survival were T stage, N stage, tumor location, VNI, and LVI (Table 3). The independent factors affecting the relapse-free survival were T stage, N stage, venous invasion (VNI), PNI, and LVI (Table 4).

Studies regarding volume outcomes are ongoing. There is no consensus regarding whether hospital volume or surgeon volume affects the long-term outcomes of cancer treatment, but Birkmeyer et al reported lower operative mortality and a better survival rate in high-volume hospitals with selected cancer resection (13). For gastric cancer, Coupland et al reported lower short-term and long-term mortality in rates high-volume hospitals for esophageal and gastric cancer (7). Thus, based on the evidence, the centralization of gastric cancer treatment in high-volume centers is performed, as well as in South Korea. However, others report no positive effect of volume (14–18). There are a limited number of studies concerning the relationship between individual surgeon volume and long-term outcomes of gastric cancer.

Regarding the size of the hospital in terms of the number of beds, Dong-rae Paik Hospital is a small-sized hospital with a total of 220 beds, 14 medical departments including internal medicine and surgery, and 10 beds in the intensive care unit. Our study analyzed the outcomes of 10 years of gastric cancer treatment performed in this hospital, and when these 10 years were divided into two periods, P2 showed the outcome of accumulated surgeon volume compared to P1 since all the surgeries were performed by one surgeon. Our study offers a result of the relationship between individual surgeon volume and long-term outcomes of gastric cancer.

Compared with studies conducted in large-sized hospitals with more than 1000 beds, Hyung et al. reviewed 5374 patients who underwent gastric cancer surgery from 1989 to 1999. The 5-year overall survival rate was 94.2% for stage I cancer, 73.4% for stage II, and 44.7% for stage III. The postoperative overall mortality rate was 0.7% (19). Park et al. reviewed 933 patients from 1997 to 2001 and reported a 5-year overall survival rate of 96% for stage Ia, 92% for stage Ib, 72% for stage II, 54% for stage IIIa, and 34% for stage IIIb. The total postoperative morbidity rate was 3.9% and the postoperative mortality rate was 0.6% (20). In our study, the total postoperative morbidity and major complication rates, as well as the postoperative mortality rate, were 11.9%, 4.1%, and 0.36%, respectively. For the long-term results, the 5-year overall survival rate at each stage was 97.8% for stage I, 82.6% for stage II, and 43.4% for stage III. Our results were comparable with those of large-sized hospitals.

Given the changes between the two periods, less PNI and LVI were detected in P2 than in P1. This lower detection of PNI and LVI may be related to the difference in the distribution of T stage (21). PNI has been regarded as an independent prognostic factor for overall survival and relapse-free survival in other studies (22–24), as well as LVI (25). In our multivariate analysis, T stage, N stage, VNI, PNI, and LVI were independent factors related to relapse-free survival, which corresponded to previous studies (20, 24–26). Although those factors may have influenced relapse-free survival over the entire period, it is difficult to determine that those factors had a significant effect on the reduction in relapse-free survival between the two periods. BMI was higher in P2 than in P1, and some studies report that BMI could be an independent factor for long-term survival after surgical treatment for gastric cancer (27, 28). In our study, the average BMI difference between the two periods was only 0.5, and Voglino et al. suggested that BMI does not affect postoperative complications or long-term survival (29).

Since LADG was first introduced by Kitano in 1994, LADG for early gastric cancer has increased in South Korea (30, 31). Dong-rae Paik Hospital began implementing LADG in 2003 and the rate of LADG rose to 18% in P2. This led to a shortening of hospital stay (32). At the beginning of LADG implementation, extended D2 lymph node dissection was not a standard procedure. Therefore, the proportion of D1 lymph node dissection seems to have been increased as LADG increased. Although LADG started mainly in P2, You et al. reported that the short-term outcomes of LADG for gastric cancer by a trained beginner surgeon were comparable with those of open surgery performed by an experienced surgeon (33), which was also seen in our study. There was a significant difference between the two periods in terms of the number of harvested lymph nodes (27.2 vs 41.4, p < 0.001). This seems to be the contribution of the development in pathology and the replacement of pathologists, rather than an increase in the number of lymph nodes actually harvested.

Mamidanna et al. reported that postoperative morbidity and mortality decreased as the surgeon volume increased (9), but in our study, there was no significant difference in postoperative morbidity or major complications as the individual surgeon volume accumulated.

There was no significant difference in the overall survival rate between the two periods, but the relapse-free survival rate was higher in P2 than in P1. Park et al. analyzed 12 years of gastric cancer treatment in a single center and reported that increasing the early detection of gastric cancer increased the overall survival rate (20). However, in our study, there was no difference in the distribution of the total stage between the two periods. We presumed that accumulated surgeon volume was associated with lower relapse-free survival rates in P2.

In South Korea, the standardization of management and assessment of treatment are being performed based on hospital volume as well (34). However, regarding these efforts, hospital size, not volume, tends to be the major factor for Koreans in terms of hospital selection, which led to large-sized and capital concentration despite gastric cancer occurring evenly in all geographical areas in Korea. This led to the distortion of the medical delivery system and delay of surgical treatment (16). In our study, even in the small-sized hospital, the well-trained surgeon showed good results in gastric cancer treatment, and as the surgeon volume accumulated over time, the long-term outcomes improved. It is hard to say that the accumulated surgeon volume directly affects long-term outcomes, but it seems to have been combined with the improvement in surgical skills and technical development as well as the introduction of adjuvant chemotherapy. Nevertheless, our study may have implications for the current Korean social atmosphere. Rather than focusing on the expansion of hospital size for attracting patients, improving the quality of treatment through the training of experienced surgeons and the intensive management of patients should be considered.

Our study has some limitations. First, this study was a retrospective study in a single center, in which there may have been information bias due to errors in information collection. Second, this study was not a head-to-head comparison study but a single-arm study with reviewing of other articles that did not include standardization or control of patients; in addition, the definition of terms was different. Third, the last follow-up was 2013, and the follow-up duration was shorter in P2 than in P1. Because there were patients lost to follow-up, Dong-rae Paik Hospital was absorbed into another hospital. Fourth, although there is a consensus for adjuvant chemotherapy based on oral S-1 or capecitabine plus oxaliplatin in advanced gastric cancer after gastrectomy recently (35, 36), standardization of adjuvant chemotherapy for gastric cancer was not established before 2010. The lack of evidence-based adjuvant chemotherapy in our study did not provide information on how long-term outcomes were affected.

Our study showed that the short-term outcomes and long-term outcomes of gastric cancer treatment in a small-sized hospital were comparable to those of large-sized hospitals. Although short-term outcomes did not improve as surgeon volume accumulated, accumulated individual surgeon volume was related to a high relapse-free survival rate. Surgeon volume should be considered more valuable than the size of the hospital in terms of gastric cancer treatment.

IV: Intravenous, LN: Lymph node, LADG: Laparoscopic-assisted distal gastrectomy, HR: Hazard ratio, CI: Confidence interval, BMI: Body mass index, PNI: Perineural invasion, LVI: Lymphatic invasion, VNI: Venous invasion, P1: period 1 (2000-2005), P2: period 2 (2006-2010)

Ethics approval and consent to participate

This study was approved by the Institutional Review Board of Busan Paik Hospital, Inje University, Busan, Republic of Korea (IRB no 19-0189)

Consent for publication

Not applicable

Availability of data and materials

The data used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Competing interests

The authors declare that they have no competing interests.

Funding

The authors declare that they have no funding

Authors’ contributions

SHS contributed to the study conception and design. JYJ and KHK contributed to the development of methodology. KHK and JSK contributed to the acquisition of data. HJB contributed to the analysis and interpretation of data. JYJ and KHK contributed equally to the writing, review, and/or revision of the manuscript as 1^st author. SHO contributed to the administrative, technical, or material support. SHS contributed to the study supervision. MSA, SHK, and YHP had other relevant contributions to the study. All authors read and approved the final manuscript.

Acknowledgments

Not applicable

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.
Begg CB, Cramer LD, Hoskins WJ, Brennan MF. Impact of hospital volume on operative mortality for major cancer surgery. JAMA. 1998;280(20):1747–51.
Hannan EL, Radzyner M, Rubin D, Dougherty J, Brennan MF. The influence of hospital and surgeon volume on in-hospital mortality for colectomy, gastrectomy, and lung lobectomy in patients with cancer. Surgery. 2002;131(1):6–15.
Birkmeyer JD, Stukel TA, Siewers AE, Goodney PP, Wennberg DE, Lucas FL. Surgeon volume and operative mortality in the United States. N Engl J Med. 2003;349(22):2117–27.
Wenner J, Zilling T, Bladstrom A, Alvegard TA. The influence of surgical volume on hospital mortality and 5-year survival for carcinoma of the oesophagus and gastric cardia. Anticancer Res. 2005;25(1B):419–24.
Dikken JL, Dassen AE, Lemmens VE, Putter H, Krijnen P, van der Geest L, et al. Effect of hospital volume on postoperative mortality and survival after oesophageal and gastric cancer surgery in the Netherlands between 1989 and 2009. Eur J Cancer. 2012;48(7):1004–13.
Coupland VH, Lagergren J, Luchtenborg M, Jack RH, Allum W, Holmberg L, et al. Hospital volume, proportion resected and mortality from oesophageal and gastric cancer: a population-based study in England, 2004–2008. Gut. 2013;62(7):961–6.
Thomson IG, Gotley DC, Barbour AP, Martin I, Jayasuria N, Thomas J, et al. Treatment results of curative gastric resection from a specialist Australian unit: low volume with satisfactory outcomes. Gastric Cancer. 2014;17(1):152–60.
Mamidanna R, Ni Z, Anderson O, Spiegelhalter SD, Bottle A, Aylin P, et al. Surgeon Volume and Cancer Esophagectomy, Gastrectomy, and Pancreatectomy: A Population-based Study in England. Ann Surg. 2016;263(4):727–32.
Ciesielski M, Kruszewski WJ, Walczak J, Szajewski M, Szefel J, Wydra J, et al. Analysis of postoperative morbidity and mortality following surgery for gastric cancer. Surgeon volume as the most significant prognostic factor. Prz Gastroenterol. 2017;12(3):215–21.
Japanese Gastric Cancer A. Japanese classification of gastric carcinoma: 3rd English edition. Gastric Cancer. 2011;14(2):101–12.
Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205–13.
Birkmeyer JD, Sun Y, Wong SL, Stukel TA. Hospital volume and late survival after cancer surgery. Ann Surg. 2007;245(5):777–83.
Damhuis RA, Meurs CJ, Dijkhuis CM, Stassen LP, Wiggers T. Hospital volume and post-operative mortality after resection for gastric cancer. Eur J Surg Oncol. 2002;28(4):401–5.
Enzinger PC, Benedetti JK, Meyerhardt JA, McCoy S, Hundahl SA, Macdonald JS, et al. Impact of hospital volume on recurrence and survival after surgery for gastric cancer. Ann Surg. 2007;245(3):426–34.
Yun YH, Kim YA, Min YH, Park S, Won YJ, Kim DY, et al. The influence of hospital volume and surgical treatment delay on long-term survival after cancer surgery. Ann Oncol. 2012;23(10):2731–7.
Kim EY, Song KY, Lee J. Does Hospital Volume Really Affect the Surgical and Oncological Outcomes of Gastric Cancer in Korea? J Gastric Cancer. 2017;17(3):246–54.
Lee HH, Son SY, Lee JH, Kim MG, Hur H, Park DJ. Surgeon's Experience Overrides the Effect of Hospital Volume for Postoperative Outcomes of Laparoscopic Surgery in Gastric Cancer: Multi-institutional Study. Ann Surg Oncol. 2017;24(4):1010–7.
Hyung WJ, Kim SS, Choi WH, Cheong JH, Choi SH, Kim CB, et al. Changes in treatment outcomes of gastric cancer surgery over 45 years at a single institution. Yonsei Med J. 2008;49(3):409–15.
Park CH, Song KY, Kim SN. Treatment results for gastric cancer surgery: 12 years' experience at a single institute in Korea. Eur J Surg Oncol. 2008;34(1):36–41.
Duraker N, Sisman S, Can G. The significance of perineural invasion as a prognostic factor in patients with gastric carcinoma. Surg Today. 2003;33(2):95–100.
Tianhang L, Guoen F, Jianwei B, Liye M. The effect of perineural invasion on overall survival in patients with gastric carcinoma. J Gastrointest Surg. 2008;12(7):1263–7.
Selcukbiricik F, Tural D, Buyukunal E, Serdengecti S. Perineural invasion independent prognostic factors in patients with gastric cancer undergoing curative resection. Asian Pac J Cancer Prev. 2012;13(7):3149–52.
Deng J, You Q, Gao Y, Yu Q, Zhao P, Zheng Y, et al. Prognostic value of perineural invasion in gastric cancer: a systematic review and meta-analysis. PLoS One. 2014;9(2):e88907.
Hyung WJ, Lee JH, Choi SH, Min JS, Noh SH. Prognostic impact of lymphatic and/or blood vessel invasion in patients with node-negative advanced gastric cancer. Ann Surg Oncol. 2002;9(6):562–7.
Yoo CH, Noh SH, Shin DW, Choi SH, Min JS. Recurrence following curative resection for gastric carcinoma. Br J Surg. 2000;87(2):236–42.
Wada T, Kunisaki C, Ono HA, Makino H, Akiyama H, Endo I. Implications of BMI for the Prognosis of Gastric Cancer among the Japanese Population. Dig Surg. 2015;32(6):480–6.
Lianos GD, Bali CD, Glantzounis GK, Katsios C, Roukos DH. BMI and lymph node ratio may predict clinical outcomes of gastric cancer. Future Oncol. 2014;10(2):249–55.
Voglino C, Di Mare G, Ferrara F, De Franco L, Roviello F, Marrelli D. Clinical and Oncological Value of Preoperative BMI in Gastric Cancer Patients: A Single Center Experience. Gastroenterol Res Pract. 2015;2015:810134.
Kitano S, Iso Y, Moriyama M, Sugimachi K. Laparoscopy-assisted Billroth I gastrectomy. Surg Laparosc Endosc. 1994;4(2):146–8.
Kim HH, Hyung WJ, Cho GS, Kim MC, Han SU, Kim W, et al. Morbidity and mortality of laparoscopic gastrectomy versus open gastrectomy for gastric cancer: an interim report–a phase III multicenter, prospective, randomized Trial (KLASS Trial). Ann Surg. 2010;251(3):417–20.
Yasunaga H, Horiguchi H, Kuwabara K, Matsuda S, Fushimi K, Hashimoto H, et al. Outcomes after laparoscopic or open distal gastrectomy for early-stage gastric cancer: a propensity-matched analysis. Ann Surg. 2013;257(4):640–6.
You YH, Kim YM, Ahn DH. Beginner Surgeon's Initial Experience with Distal Subtotal Gastrectomy for Gastric Cancer Using a Minimally Invasive Approach. J Gastric Cancer. 2015;15(4):270–7.
Lee JH, Kim JG, Jung H-K, Kim JH, Jeong WK, Jeon TJ, et al. Synopsis on Clinical Practice Guideline of Gastric Cancer in Korea: An Evidence-Based Approach. The Korean Journal of Gastroenterology. 2014;63(2).
Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, et al. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007;357(18):1810–20.
Noh SH, Park SR, Yang H-K, Chung HC, Chung I-J, Kim S-W, et al. Adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): 5-year follow-up of an open-label, randomised phase 3 trial. The Lancet Oncology. 2014;15(12):1389–96.

Table 1. Demographics of the patients’ clinicopathologic characteristics

		Total Period N=820(%)	Period 1 N=407(%)	Period 2 N=413(%)	p-value
Age		58.8±11.04	58.34±10.75	59.30±11.30	0.215
Sex	Male	544(66.3)	269(66.1)	275(66.6)	0.881
Sex	Female	276(33.7)	138(33.9)	138(33.4)	0.881
BMI (kg/m²)		22.71±3.13	22.49±3.01	22.93±3.24	0.041
Tumor location	Low	493(60.3)	239(58.7)	254(61.8)	0.848
	Middle	193(23.6)	104(25.6)	89(21.7)
	Upper	125(15.3)	63(12.5)	62(15.1)
	Whole	7(0.9)	1(0.2)	6(1.5)
T stage	T1	490(59.8)	230(56.5)	260(63.0)	0.042
	T2	85(10.4)	41(10.1)	44(10.7)
	T3	223(27.2)	125(30.7)	98(23.7)
	T4	22(2.7)	11(2.7)	11(2.7)
N stage	N0	545(66.5)	264(64.9)	281(68.0)	0.544
	N1	85(10.4)	45(11.1)	40(9.7)
	N2	76(9.3)	42(10.3)	34(8.2)
	N3	114(13.9)	56(13.8)	58(14.0)
Stage	Stage 1	522(63.7)	246(60.4)	276(66.8)	0.117
	Stage 2	129(15.7)	72(21.9)	57(13.8)
	Stage 3	169(20.6)	89(21.9)	80(19.4)
Histology	Differentiated	459(56.5)	234(58.4)	225(54.6)	0.440
	Undifferentiated	350(43.1)	163(40.6)	187(45.4)
	Other	4(0.5)	4(1.0)	0(0)
VNI	Yes	34(4.1)	19(4.7)	15(3.6)	0.457
VNI	No	786(95.9)	388(95.3)	398(96.4)	0.457
PNI	Yes	32(3.9)	27(6.6)	5(1.2)	<0.001
PNI	No	788(96.1)	380(93.4)	408(98.8)	<0.001
LVI	Yes	102(12.4)	71(17.4)	31(7.5)	<0.001
LVI	No	718(87.6)	336(82.6)	382(92.5)	<0.001

BMI Body mass index, VNI Venous invasion, PNI Perineural invasion, LVI Lymphatic invasion

Table 2. Short-term treatment outcomes of patients

		Total Period N=820(%)	Period 1 N=407(%)	Period 2 N=413(%)	p-value
Operation method	Open	741(90.4)	402(98.8)	339(82.1)		<0.001
	LADG	79(9.6)	5(1.2)	74(17.9)
Resection extent	Subtotal	662(80.7)	331(81.3)	331(80.1)		0.743
	Total	155(18.9)	74(18.2)	81(19.6)
	Other	3(0.4)	2(0.5)	1(0.2)
LN dissection level	D1	36(4.4)	2(0.5)	34(8.2)		<0.001
	D1+	362(44.1)	181(44.5)	181(43.8)
	D2	422(51.5)	224(55.0)	198(47.9)
Harvested LN		34.40±16.44	27.21±12.07	41.48±17.10		<0.001
Adjuvant chemotherapy	None	160(19.5)	62(15.2)	98(23.7)
	Oral	442(53.9)	182(44.7)	260(63.0)		<0.001
	IV	218(26.6)	163(40.0)	55(13.3)
Hospital stay		16.32±12.54	18.04±14.68	14.61±9.70		<0.001
Postoperative morbidity*	G1-2	64(7.8)	34(8.4)	30(7.3)		0.942
	G3-4	34(4.1)	16(3.9)	18(4.4)
	None	722(88.0)	357(87.7)	365(88.4)

LN Lymph node, LADG Laparoscopic-assisted distal gastrectomy

*Postoperative morbidity classified by Clavien-Dindo classification

Table 3. Univariate and multivariate analyses of risk factors for overall survival

Variable	Univariate		Multivariate
	HR (95% CI)	p-value	HR (95% CI)	p-value
Period	1.127 (0.762-1.668)	0.549
Age	1.013 (0.997-1.030)	0.110
BMI (kg/m²)	0.987 (0.932-1.045)	0.649
T stage
T1 vs T2	3.991 (1.523-10.458)	0.005	3.832 (1.788-8.213)	0.001
T1 vs T3	5.696 (1.674-19.376)	0.005	6.490 (3.330-12.650)	0.000
T1 vs T4	9.937 (2.578-38.303)	0.001	12.802 (5.396-30.373)	0.000
N stage
N0 vs N1	1.670 (0.777-3.590)	0.189	1.724 (0.895-3.319)	0.103
N0 vs N2	1.326 (0.345-5.091)	0.681	2.239 (1.193-4.200)	0.012
N0 vs N3	1.856 (0.464-7.426)	0.382	3.516 (1.937-6.381)	0.000
Stage
stage 1 vs stage 2	1.007 (0.293-3.462)	0.991
stage 1 vs stage 3	1.965 (0.261-14.796)	0.512
Tumor location
Low vs Middle	0.635 (0.374-1.077)	0.092	0.618 (0.367-1.041)	0.071
Low vs Upper	1.338 (0.873-2.050)	0.182	1.336 (0.885-2.018)	0.168
Low vs Whole	2.841 (0.980-8.232)	0.054	2.508 (0.931-6.760)	0.069
Histology
Diff vs Undiff	1.324 (0.914-1.916)	0.138
Diff vs Unknown	1.839 (0.424-7.983)	0.416
VNI	1.966 (1.094-3.535)	0.024	1.948 (1.113-3.410)	0.020
PNI	0.793 (0.436-1.442)	0.447
LVI	2.570 (1.697-3.890)	0.000	2.394 (1.641-3.465)	0.000

HR Hazard ratio, CI Confidence interval, BMI Body mass index, Diff Differentiated, Undiff Undifferentiated, VNI Venous invasion, PNIPerineural invasion, LVI Lymphatic invasion,

Table 4. Univariate and multivariate analyses of risk factors for relapse-free survival

Variable	Univariate		Multivariate
	HR (95% CI)	p-value	HR (95% CI)	p-value
Period	0.845 (0.528-1.353)	0.483
Age	0.997 (0.978-1.016)	0.739
BMI (kg/m²)	1.013 (0.950-1.080)	0.688
T stage
T1 vs T2	3.708 (1.036-13.267)	0.044	3.072 (1.127-8.377)		0.028
T1 vs T3	8.703 (1.808-41.896)	0.007	7.471 (3.274-17.050)		0.000
T1 vs T4	17.147 (3.098-94.908)	0.001	14.548 (5.508-38.427)		0.000
N stage
N0 vs N1	2.168 (0.871-5.396)	0.096	2.137 (0.972-4.696)		0.059
N0 vs N2	2.182 (0.483-9.869)	0.311	2.705 (1.290-5.674)		0.008
N0 vs N3	2.996 (0.640-14.028)	0.164	3.803 (1.872-7.727)		0.000
Stage
stage 1 vs stage 2	0.774 (0.158-3.794)	0.752
stage 1 vs stage 3	1.128 (0.102-12.442)	0.922
Tumor location
Low vs Middle	0.818 (0.466-1.438)	0.486
Low vs Upper	0.778 (0.458-1.322)	0.353
Low vs Whole	2.215 (0.687-7.138)	0.183
Histology
Diff vs Undiff	0.984 (0.644-1.504)	0.940
Diff vs Unknown	2.073 (0.468-9.192)	0.337
VNI	2.743 (1.472-5.113)	0.001	2.415 (1.378-4.232)		0.002
PNI	1.604 (0.899-2.862)	0.110	1.877 (1.125-3.131)		0.016
LVI	1.966 (1.235-3.130)	0.004	2.249 (1.469-3.442)		0.000

HR Hazard ratio, CI Confidence interval, BMI Body mass index, Diff Differentiated, Undiff Undifferentiated, VNI Venous invasion, PNIPerineural invasion, LVI Lymphatic invasion,

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Long-term outcomes of gastric cancer in a single small center: a retrospective analysis

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Abstract

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Background

Materials And Methods

Patients

Clinical outcomes

Statistical analysis

Results

Clinicopathologic characteristics

Short-term treatment outcomes

Long-term treatment outcomes

Multivariate analysis

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