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Operative Risk Factors in Gastric Cancer

Surgery for Elderly Patients

by

Su Han Seo

Major in Medicine

Department of Medical Sciences

The Graduate School, Ajou University

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Operative Risk Factors in Gastric Cancer

Surgery for Elderly Patients

by

Su Han Seo

A Dissertation Submitted to The Graduate School of

Ajou University in Partial Fulfillment of the

Requirements for the Degree of Master of Medicine

Supervised by

Sang Uk Han, M.D., Ph.D.

Major in Medicine

Department of Medical Sciences

The Graduate School, Ajou University

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This certifies that the dissertation

of Su Han Seo is approved.

SUPERVISORY COMMITTEE

Sang Uk Han

Yong Kwan Jo

Hoon Hur

The Graduate School, Ajou University

December, 20th, 2011

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i - ABSTRACT -

Operative Risk Factors in Gastric Cancer Surgery

for Elderly Patients

Purpose: Gastric cancer surgery is popular operation in East Asia like Korea and Japan.

Recently, population of elderly has been significantly increased. As results, surgery for gastric cancer surgery for elderly will be also increased. We evaluated the effect of old age on gastric cancer surgery, and analyzed the operative risk factors for elderly patients.

Method & methods: From November 2008 to August 2010, 590 patients who were

underwent curative resection for gastric cancers were enrolled. Patients who underwent palliative surgery or emergency operations were excluded, and we analyzed the correlation between surgical outcomes and age retrospectively. We defined that elderly was patients with over 65 year old.

Results: Mean age of all patients was 58.3 year old, and complications were occurred in 87

cases (14.7%). Most common complication was wound infection and severe complication which required surgical, endoscopic or radiologic intervention were developed in 52 cases (8.8%).

As patients’ age increase, complication rate also have been increased. In univariate analysis, age, comorbidity, extend of resection, operation time and combined resection were correlated with surgical complication. Especially, age with over 75 year old, operation time and comorbidity were predictive factors in multivariate analysis. In the elderly, comorbidity and extend of resection was related with surgical complication.

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Conclusions: Patients’ age was most important factor for predicting surgical complications.

Surgeon should pay an attention to perform gastric cancer surgery for elderly. In particularly, total gastrectomy has to be performed carefully for elderly who have comorbidity.

Key wards: Stomach cancer, Risk factor, Gastrectomy, Complication

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TABLE OF CONTENTS

ABSTRACT ··· i

TABLE OF CONTENTS ··· iii

LIST OF FIGURES ··· iv

LIST OF TABLES ··· v

Ⅰ. INTRODUCTION ··· 1

Ⅱ. MATERIALS AND METHODS ··· 3

Ⅲ. RESULTS ··· 5

Ⅳ. DISCUSSION ··· 13

Ⅴ. CONCLUSION ··· 17

REFERENCES ··· 18

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iv

LIST OF FIGURES

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v

LIST OF TABLES

Table 1. Distribution of major postoperative complications and mortality of a total Of 87 cases(14.7%) ··· 8

Table 2. Correlation between clinical factors and complication ··· 9

Table 3. Multivariable analysis for risk factors of postoperative complication ··· 10

Table 4. Correlation between clinic-operative factors and complication in elderly patients (≥ 65 years old ) ··· 11

Table 5. Comparison of predicting factors for postoperative complication between subgroups according to age ··· 12

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1

. INTRODUCTION

Gastric cancer is most common malignancy in Korea, and second cause of malignant-related death in the world.(Stewart and Kleihues, 2003) Only proven method to increase the survival of gastric cancer patients is curatively to resect the primary tumor and proper range of lymph node. Conventional surgical modality is the subtotal or total gastrectomy and extended lymph node dissection as well as combined resection of adherent organ as occasion demands under open laparotomy.(Okamura et al., 1988; Fukagawa et al., 2001) However, surgical treatment has been recently developed to tending towards the improvement of quality of life (QOL) and early recovery. In Korea, the rate of postoperative complication after gastric cancer surgery has been reported as 10.5% to 14.7%.(Kim et al.; Park et al., 2005) The elderly has been presented as one of factors related to complication in these clinical researches which evaluated the risk factors.(Wu et al., 2000; Otsuji et al., 2005)

The elderly are the faster growing part of the entire population in Korea. According to the annual report of the Korea National Statistical Office in 2007, the proportion of elderly over 65 years old was 9.9%, so called ‘aging society’ defined by World Health Organization (WHO). Therefore, the proportion of the elderly in the patients who diagnosed with gastric cancer and underwent gastric cancer surgery is expected to be increased. The elderly have a functional diminution of reserve capacity, and show the high incidence of comorbidity. These may lead to reduce the older patient’s ability to tolerate surgical stress including gastric cancer surgery. The other feature of elderly is a

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fewer social and economical support and more burden to additional fee following with postoperative complication. In the way of physicians, clinical practices for the elderly should be performed cautiously in order to minimize the postoperative complication, and it is important to become aware of the risk factors for complication in the elderly patients.

In this study, we aimed to find out the factors to predict the complications after gastric cancer surgery through retrospective review of the patients who have been undergone in single institution of Korea during 2 years.

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II. MATERIAL AND METHODS

We reviewed the clinical information, operation and progress records, and pathologic results of 590 patients who were diagnosed with gastric cancer and undergone curative gastrectomy with proper lymph node dissection from November 2008 to August 2010 in Ajou University Hospital, Suwon, Korea. All patients were diagnosed with adenocarcinoma by gastrofiberscopic biopsy, and the patients with clinically early disease were undergone the operation by minimally invasive surgery including laparoscopic or robotic approach. Total or subtotal gastrectomy were performed considering the location of tumor to secure a resection margin with free from tumor, and the lymph nodes of over D1+beta lesions were dissected according to the classification suggested by the Japanese Gastric Cancer Association.(Japanese Gastric Cancer, 1998) The combined resection was deemed to completely remove the adherent organ including distal pancreas or spleen invaded by tumor or to treat other disease like gall stone and other malignancy.

At the postoperative period, all patients were managed with common clinical pathway. Prophylactic antibiotics was injected during two postoperative days, and patients were supplied the soft diet from the 5th postoperative day. Patients were recommended the discharge from hospital two days after they ingested soft diet without intolerance. When the event to increase the length of hospital stay and delay the schedule of diet during hospital periods, we defined it as postoperative complications.

We defined the patients with over 65 years old as the elderly. We analyzed the correlation between the clinicopathologic results including patients’ age and the

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postoperative complication. In addition, subgroup analysis for the elderly was performed to find out the risk factors for the postoperative complication.

Statistical analysis was performed using Statistical Package for the Social Sciences version 13.0 (SPSS Inc. CA). Univariate analysis was done using Pearson’s chi-square test, and multivariate analysis was carried out using binary multiple linear regressions analysis. A p value of <0.05 was considered statistically significant.

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III. RESULTS

Mean age of patients was 58.3 year olds. When the age of patients was classified into 5 years, the number of patients from 60 to 65 year old was most frequent (Fig 1). Of total 590 patients, 203 (34.4%) patients were proved to be the elderly in our study. And the number of the patients over 75 years old was 42 (7.1%).

The postoperative complication was occurred in 87 patients (14.7%), most common is wound problem including seroma, infection and dehiscence. Besides, sixteen patients have postoperative prolonged ileus, fourteen bleeding from intraabdomen or intraluminal and nine pneumonia as frequent complications (Table 1). Sever complications were occurred in 52 patients (8.8%) who should be managed with radiologic, endoscopic intervention or surgical procedure under general anesthesia. Postoperative mortality was occurred in 4 patients (0.67%).

We evaluated the correlation between the complications and the clinical factors. The patients’ age (p=0.024), comorbdity (p=0.011) and the extension of resection (p=0.008) and operation time (p=0.008), and combined resection (p=0.010) are significantly related with postoperative complication (Table 2). Specifically, the increasing age was significantly related with complications when we divided the patients’ age into three groups (below 65, from 66 to 75, above 76).

When we analyzed the multivariate analysis to find out the factors for predicting the postoperative complications, the age over 75 years (OR=2.353, p=0.023), operation time (OR=1.923, p=0.008) and comorbidity (OR=1.674, p=0034) are pertained to the here

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6 (Table 3).

In addition, we performed subgroup analysis objected to the 204 patients over 65 years old. One hundred fifty five patients have the comorbidity, and the complication was occurred in 27.7% of the elder with comorbidity. As a result, the comorbidity was only factor related to the postoperative complication in the univariate(p=0.031) and multivariate analysis(OR=2.683, p=0.038) (Table 4,5). Meanwhile, the operative time was only factor for prediction it in the patients under 65 years (OR=2.32, p=0.012) (Table 5).

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Table 1. Distribution of major postoperative complications and mortality of total 87 cases (14.7%) Complication n % Total complication 87 14.7% Wound infection 21 24.3% Postoperative ileus 16 18.3% Bleeding 14 16.1% Pulmonary complication 9 10.3% Mortality 4 0.7%

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Table 2. Correlation between clinic-operative factors and complication V Vaarriiaabblleess n Complication cases (%) P-value A Aggee < <6655 7 755>>,,≥≥6655 ≥ ≥7755 3 38877 1 16611 4 422 5 599((1155..22%%)) 3 333((2200..55%%)) 1 133((3311..00%%)) 0 0..002244 G Geennddeerr Male Female 420 170 77 (18.3%) 28 (16.5%) 0.592 B BMMII ((kkgg//mm22)) <25 ≥25 417 168 75 (18.0%) 27 (16.1%) 0.581 C Coommoorrbbiiddiittyy YYeess N Noonnee 3 34455 2 24455 7 733((2211..22%%)) 3 322((1133..11%%)) 00..001111 R Reesseeccttiioonn TToottaallggaassttrreeccttoommyy P Paarrttiiaallggaassttrreeccttoommyy 1 10088 4 48822 2 299((2266..99%%)) 7 766((1155..88%%)) 00..000066 A Apppprrooaacchh Conventional Minimal invasive 310 280 63 (20.3%) 42 (15.0%) 0.091 O Oppttiimmee((mmiinn)) <<118800 ≥ ≥118800 2 22266 3 35577 2 288((1122..44%%)) 7 755((2211..00%%)) 00..000088 C Coommbbiinneedd r reesseeccttiioonn Y Yeess N Noonnee 7 733 5 51144 2 211((2288..88%%)) 8 844((1166..33%%)) 00..001100 L LNNddiisssseeccttiioonn D1 (α or β) D2 335 253 53 (15.8%) 51 (20.2%) 0.172 BMI=body mass index, LN=ly,mph node

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Table 3. Multivariable analysis for risk factors of postoperative complication

Variables P-value Odd

Ratio 95% C.I. Age < 65 vs 75 >, ≥ 65 < 65 vs ≥ 75 0.442 0.023 1.219 2.353 0.736 - 2.017 1.125 – 4.920 Op time < 180 minutes vs ≥ 180 minutes 0.008 1.923 1.184 – 3.123

Comorbidity None vs yes 0.034 1.674 1.038 – 2.699

Combined

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Table 4. Correlation between clinic-operative factors and complication in elderly patients (≥ 65 years old )

Variables n Complication case (%) P-value Age < 75 ≥ 75 161 42 36 (22.4%) 13 (31.0%) 0.311 Gender Male Female 155 48 37 (23.9%) 11 (25.0%) 0.961 BMI <25 ≥25 138 60 34 (24.6%) 12 (20.0%) 0.478 Comorbidity Yes None 155 48 43 (27.7%) 6 (12.5%) 0.031 Resection Total gastrectomy

Partial gastrectomy 33 170 12 (36.4%) 37 (21.8%) 0.073 Approach Conventional Minimal invasive 113 90 31 (27.4%) 168 (17.8%) 0.465 Op time <180 ≥180 83 116 16 (19.3%) 32 (27.6%) 0.177 Combined resection Yes None 36 166 12 (33.3%) 34 (20.5%) 0.096 LN dissection D1 (α or β) D2 121 80 30 (24.8%) 18 (22.5%) 0.709 BMI=body mass index, LN=lymph node

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Table 5. Comparison of predicting factors for postoperative complication between subgroups according to age

< 65 years old ≥ 65 years old Variables P-value Odd

Ratio 95% C.I. Variables P-value Odd Ratio 95% C.I. Op time < 180 minutes vs ≥ 180 minutes 0.012 2.32 1.204-4.470 Comorbidity None vs yes 0.038 2.683 1.054-6.833 Combined op None vs yes 0.074 2.100 0.931-4.735

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IV. DISCUSSION

The elderly has been well known as the risk factors for postoperative complication in various surgical fields, because of the loss of physical function. We confirmed the results though the analysis for the records of patients who underwent gastric cancer surgery in single center during two years. Moreover, we obtained additional information in which the patients with comorbidity had only risk for complication in the elderly.

Although the definition of elderly patients varies according the social and economic situation, most developed and developing countries have defined the elderly as those aged 65 years because of the decreased role in the community and society.(HelpAge International. et al., 1999) On the other hand, the elderly is medically defined in accordance with the functional loss of major organs and decreased ability of recovery from severe stress like trauma. In particular, because several clinical researches that patients with the age 75 years have higher frequency of comorbidity and severe loss of physical function,(Neugarten et al., 1965; Wu et al., 2000) the definition of “young elderly” is over aged 65 and “old elderly” as over aged 75 years.(Hazzard and Burton, 1987; Williams, 1998) We assumed that increased complication after gastric cancer surgery may also be effected by increased age, because it requires surgical resection of extensive range and reconstruction in upper abdomen. In present study, we analyzed the correlation between postoperative complications and clinical factors including the patients’ age which was divided by age 65 and 75 years. As a result, age over 75 years was a strongest predicting factor for postoperative complication in gastric cancer surgery.

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There have been several studies reporting that postoperative morbidity and mortality can be increased in the elderly.(Winslet et al., 1996; Katai et al., 2004; Kunisaki et al., 2006) Researchers suggested that the reduced range of surgery and minimally invasive treatment like endoscopic therapy could be applied for the elderly patients as alternative method replacing standard surgery. However, the number of the elderly requiring gastric cancer surgery would be increase following with increased number of the elderly, and we can’t make it avoid standard surgery in all elderly patients. Therefore, it can be important to evaluate the surgical risk of the elderly and find out the elderly who may be suitable for limited surgery or minimally invasive treatment. In subgroup analysis objected to the only elderly, the comorbidity was higher risk factor than the old elderly patients.

We confirmed that the biological age of patients considering the organic function was more informative for postoperative complication after gastric cancer surgery than physical age in our study. Major comorbidity in our study was hypertension, diabetic mellitus and pulmonary problem, and the 58.4% of all patients had one and more kinds of comorbidity. The proportion of patients with comorbidity was increased into 76.4% in the elderly over 65 years. Meanwhile the comorbidity was not predicting factor for postoperative complication in the patients under 65 years, it was only factor for the patients over 65 years. It means that comoribidity can give an more effect on the complication in the elderly patients. To date, there have been several reports about the effect of the comorbidity on the gastric cancer surgery,(Rim et al., 1997; Sorensen et al., 2005; Matsuda et al., 2009) and Kim et al.(Kim et al., 2008b) announced that the comorbidity was significantly related to the postoperative complication after laparoscopic

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surgery for gastric cancer in the multicenter study objected to 1,237 patients. However, there has been no study which analyzed the effect of comorbidity on the increasing age in the postoperative complication objected to the all kinds of gastric cancer surgery.

In present study, 280 (47.5%) of total 590 underwent minimally invasive surgery (MIS) by the laparoscopic or robotic approach. Although recent indication for MIS was early disease of gastric cancer, it is expected its indication to be expended due to the increasing number of early disease and the development of technique and instruments.(Kitagawa et al., 2005) Regarding MIS for the elder, there has been controversy about whether this procedure can be positively or negatively effect on the surgical outcome of the elderly.(Kunisaki et al., 2009) The patients who are performed by MIS in our study showed relatively lower complication rate than open procedure, but it is not statistically significant in the elderly as well as all patients. Therefore, the efficacy of MIS for the elderly could not be confirmative from what our study present.

The development of treatment for gastric cancer has followed with the reducing the range of surgery as well as maintaining the oncologic safety.An JY, Cheong HJ, Hyung WJ, Noh SH : Recent evolution of surgical treatment for gastric cancer in korea. J Gastric Cancer 2011, 11(1):1-6 According to this principle, endoscopic resection for early gastric cancer, and partial gastric resection with limited lymph node dissection using sentinel lymph node navigation has been developed. The absolute indication of endoscopic resection was mucosal cancer under 2 cm considering the metastasis to the perigastric lymph node, (Yamao et al., 1996) but this indication has been recently extended by the effect of precise preoperative diagnosis and developing endoscopic technique (Yokoi et

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al., 2006; Gotoda, 2007). The definite advantage of endoscopic treatment is not requiring the general anesthesia. Therefore, the extended indication of endoscopic treatment could be primarily applied for the elderly which are highly expected the postoperative complication related to the anesthesia, in spite of the possibility of incomplete tumor resection and not confirmative lymph node status. Another option for preventing the postoperative complication is partial gastrectomy with limited lymph node dissection under sentinel node navigation. (Ishii et al., 2008; Lee et al., 2009) Although this procedure did not have confirmative results to apply clinical practice, future studies about it can give the researchers the clue to do it.

The three surgeons in the present study have the experience over 80 gastric cancer surgery per year, and 400 surgeries for gastric cancer patients per year has been performed in the institution. Our result in the view of complication rate is similar with the rate, 10.5 – 14.7% from the large scale studies in Korea.(Kim et al.; Kim et al., 2008a) Therefore, our result may be generally acceptable in other institutions. Merely, our study had the limitation in which long term follow-up did not performed to evaluate survival after cancer surgery. Therefore, the benefit of limited surgery or endoscopic treatment for the elderly did not reach a conclusion.

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V. CONCLUSION

As a result, the most important factor for predicting the postoperative complication after gastric cancer surgery is patient’s age, and specific caution for the elderly are required. Especially, authors suggest that surgeon performing gastric cancer surgery should consider the limited surgery or endoscopic treatment for the elderly with comorbidity if the disease status is applicable.

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REFERENCES

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2. Gotoda T: Endoscopic resection of early gastric cancer. Gastric Cancer 10: 1-11, 2007

3. Hazzard W, Burton J: Health problems of the elderly. Harrison's Principles of

Internal Medicine (11th Ed. Ch. 81). New York: McGraw-Hill, 1987

4. HelpAge International., Randel J, German T, Ewing D: The ageing and development report : poverty, independence, and the world's older people. London, Earthscan Publications, pp.xvi, 200 p., 1999

5. Ishii K, Kinami S, Funaki K, Fujita H, Ninomiya I, Fushida S, Fujimura T, Nishimura G, Kayahara M: Detection of sentinel and non-sentinel lymph node micrometastases by complete serial sectioning and immunohistochemical analysis for gastric cancer. J Exp Clin Cancer Res 27: 7, 2008

6. Japanese Gastric Cancer A: Japanese Classification of Gastric Carcinoma - 2nd English Edition. Gastric Cancer 1: 10-24, 1998

7. Katai H, Sasako M, Sano T, Fukagawa T: Gastric cancer surgery in the elderly without operative mortality. Surg Oncol 13: 235-238, 2004

8. Kim HH, Hyung WJ, Cho GS, Kim MC, Han SU, Kim W, Ryu SW, Lee HJ, Song KY: 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 251: 417-420,

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9. Kim MC, Kim W, Kim HH, Ryu SW, Ryu SY, Song KY, Lee HJ, Cho GS, Han SU, Hyung WJ: Risk factors associated with complication following laparoscopy-assisted gastrectomy for gastric cancer: a large-scale korean multicenter study. Ann

Surg Oncol 15: 2692-2700, 2008a

10. Kim W, Song KY, Lee HJ, Han SU, Hyung WJ, Cho GS: The impact of comorbidity on surgical outcomes in laparoscopy-assisted distal gastrectomy: a retrospective analysis of multicenter results. Ann Surg 248: 793-799, 2008b

11. Kitagawa Y, Kitano S, Kubota T, Kumai K, Otani Y, Saikawa Y, Yoshida M, Kitajima M: Minimally invasive surgery for gastric cancer--toward a confluence of two major streams: a review. Gastric Cancer 8: 103-110, 2005

12. Kunisaki C, Akiyama H, Nomura M, Matsuda G, Otsuka Y, Ono HA, Shimada H: Comparison of surgical outcomes of gastric cancer in elderly and middle-aged patients. Am J Surg 191: 216-224, 2006

13. Kunisaki C, Makino H, Takagawa R, Oshima T, Nagano Y, Ono HA, Akiyama H, Shimada H: Efficacy of laparoscopy-assisted distal gastrectomy for gastric cancer in the elderly. Surg Endosc 23: 377-383, 2009

14. Lee SE, Lee JH, Ryu KW, Cho SJ, Lee JY, Kim CG, Choi IJ, Kook MC, Nam BH, Park SR, Lee JS, Kim YW: Sentinel node mapping and skip metastases in patients with early gastric cancer. Ann Surg Oncol 16: 603-608, 2009

15. Matsuda K, Hotta T, Takifuji K, Yokoyama S, Higashiguchi T, Tominaga T, Oku Y, Nasu T, Tamura K, Yamaue H: Long-term comorbidity of diabetes mellitus is a risk factor for perineal wound complications after an abdominoperineal resection.

Langenbecks Arch Surg 394: 65-70, 2009

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19. Park DJ, Lee HJ, Kim HH, Yang HK, Lee KU, Choe KJ: Predictors of operative morbidity and mortality in gastric cancer surgery. Br J Surg 92: 1099-1102, 2005 20. Rim IG, Yu HC, Yang DH, Hwang YH: A Study of the Factors Related to the

Frequency of Postoperative Gomplications for Gastric Cancer. Journal of the

Korean Surgical Society 53: 341-352, 1997

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MSJPrinciples and practice of geriatric medicine. New York: John Wiley & Sons,

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26. Yamao T, Shirao K, Ono H, Kondo H, Saito D, Yamaguchi H, Sasako M, Sano T, Ochiai A, Yoshida S: Risk factors for lymph node metastasis from intramucosal gastric carcinoma. Cancer 77: 602-606, 1996

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22 - 국문요약 -

노인 위암 환자에서 수술 시 위험인자의 분석

아주대학교 대학원 의학과 서 수 한 (지도교수: 한 상 욱) 목적: 위암 수술은 한국과 일본과 같은 동 아시아에 흔히 시행되고 있고 있다. 최근 노인 인구가 급속하게 증가되고 있다. 그 결과, 노인 인구에서 위암수술 이 역시 증가 될 것이다. 이에 저자들은 위암 수술이 노인 인구에 미치는 영 향과 위험인자에 대해 알아 보고자 이 연구를 진행하였다. 방법: 2008년 11월부터 2010년 8월까지, 아주대학교 부속병원에서 완치를 목적으로 수술한 590명의 환자를 대상으로 연구를 진행했다. 완화적 수술 및 응급수술을 했던 환자들은 연구에서 제외시켰으며, 수술결과와 나이의 상관관 계를 후향적으로 분석했다. 저자들은 노인을 65세 이상으로 정의했다. 결과: 모든 환자의 평균 연령은 58.3세였고, 합병증은 모두 87(14.7%)예에 서 발생하였다. 가장 흔한 합병증은 창상감염이었고 수술적, 내시경적, 또는 방사선학적 중재적 시술이 필요한 심각한 합병증은 52(8.8%)예에서 발생했

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23 다. 환자의 나이가 증가함에 따라 합병증의 빈도도 증가했다. 단 변량 분석에 서 나이, 동반질환, 절제범위, 수술시간,동반절제 여부가 수술 후 합병증과 관 련 있는 인자로 확인되었다. 다 변량 분석에서 특히 75세 이상의 노인이 수술 시간과 동반질환여부가 수술 후 합병증의 예후 인자로 확인되었으며, 노인 인 구에서 동반 질환과 절제의 범위가 수술 합병증과 관련 있었다. 결론: 환자의 나이는 수술 후 합병증에 중요한 예후 인자이다. 집도의는 노인 환자의 위암수술에 보다 더 주의를 기울여야 하며 특히 동반 질환이 있는 노 인환자에서 위 전 절제술을 할 때 좀 더 조심스럽게 접근해야겠다. 핵심어: 위암, 예후 인자, 위 절제술, 합병증

수치

Fig. 1.    The distribution of patients’ age was presented by histogram   ·······················   7
Table 1.    Distribution of major postoperative complications and mortality of a total                    Of 87 cases(14.7%)   ····················································································  8
Fig. 1. The distribution of patients’ age was presented by histogram
Table 1. Distribution of major postoperative complications and mortality of total 87  cases (14.7%)    Complication    n    %    Total complication  87  14.7%  Wound infection    21    24.3%    Postoperative ileus    16    18.3%    Bleeding    14    16.1%
+5

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