1. 伍希元 張浩銘 詹德全 三軍總醫院外科部一般外科
Laparoscopic gastrectomy for gastric cancer: outcome analysis and Risk factors
Good afternoon, everyone. It's my pleasure to be here. Today, I would like to report the outcome analysis of laparoscopic gastrectomy for gastric cancer in Tri-service general hospital.
伍希元 張浩銘 詹德全
三軍總醫院外科部一般外科

2. background Laparoscopic gastrectomy (LG) for early gastric cancer (GC)
Comparable feasibility and oncologic safety
RCTs
Laparoscopic distal gastrectomy for clinical stage I cancer is listed as an option in Japanese guidelines 2014
Kitano Hayashi 2005
Huscher Lee 2005
Takiguchi KLASS-01
As laparoscopic distal gastrectomy was first done by Dr. Kitano in the 1990s, it has been popularized in the last two decades. Like most laparoscopic surgery, LG is associated with mini-incision, less blood loss, faster recovery, and shorter hospital stay. When it comes to its implication in gastric cancer, there are increasing reports, including several multicenter randomized controlled trials, showing its oncologic equivalency for early gastric cancer. The recent Japanese guideline in 2014 also listed laparoscopic distal gastrectomy is a treatment option for clinical stage I cancer.

3. background
Increasing evidences indicate feasibility of laparoscopic surgeries in advanced GC
Two multicenter RCTs
JCOG0912
CLASS-01
With the advancement of laparoscopic techniques, several specialized centers in east Asia countries are able to implicate LG in advanced gastric cancer. By now, there are two multicenter randomized controlled trials showing its technical safety and equivalent oncologic quality
Inaki. World J Surg (2015) 39:2734–2741
Hu. J Clin Oncol (2016) 34:

4. The applicability of LG for GC in daily practice is still unclear.
However, most studies included relative younger patients with few comorbidities. The definition of advanced gastric cancer also varied.
The applicability of LG for GC in daily practice is still unclear.
However, most of these studies with strict inclusion criteria. The subjects are often younger patients with few comorbidities, and few with locally advanced disease. The applicability of LG for gastric cancer in daily practice is still unclear

5. 2015 Cancer registry report, Taiwan
=2001
Above stage
III:
48.5%
You can see around half of the gastric cancer patients who can be operated in Taiwan are above stage III.
=727
=243

6. 2015 Cancer registry report, Taiwan
=838 / 2001
Age ≧ 70
41.9%
In addition, 41.9% of them are elderly. Here is the question, what is the application of LG on these patients? Is it safe?

7. LG in Tri-service general hospital
First LADG for EGC in 2007
First LATG for EGC in 2008
Since 2010,  totally LG (LDG, LTG) is the standard care for GC
In our hospital, Dr. Chan did the first laparoscopic assisted distal gastrectomy for early gastric cancer in 2007, and first laparoscopic assisted total gastrectomy in Since 2010, totally laparoscopic gastrectomy, either distal or total gastrectomy, is the standard care for gastric cancer.

8. Aim
To explore the short- and long-term outcome of LG for gastric cancer
Identify risk factors for early complication, to optimize patient selection and perioperative care
So, the aim of this study is to explore the short- and long-term outcome of LG for gastric cancer. Also, we identify risk factors for early complication, in order to optimize patient selection and perioperative care.

9. Material and methods A retrospective case-control study
, 247 patients underwent laparoscopic gastrectomy for gastric cancer in TSGH
245 included after excluding 2 patients with palliative surgery
Analyze data of patient demographics, perioperative outcome, pathology and long-term outcome
This is a retrospective case-control study. We included 245 patients from , and analyze data of patient demographics, perioperative outcome, pathology and long-term outcome.

10. Clinicopathologic characteristics
Patient characteristics
Age
65.2±14.8
Gender (M:F)
160:85 (65.3%:34.7%)
BMI
23.9±3.4
Preop albumin (mg/dl)
3.8±0.5
Comorbidities
147 (60.0%)
CCI
<5
68 (27.8%)
5-7
145 (59.2%) ≧8
32 (13.1%)
ASA score 1
62 (25.3%) 2
136 (55.5%) ≧3
47 (19.2%)
Hx. of abdominal surg.
Neoadjuvant chemotherapy
9 (3.3%)
Surgical characteristics
Procedure
Distal gastrectomy
175 (71.4%)
Total gastrectomy
70 (28.6%)
Extent of LN dissection D1
5 ( 2.0%)
D1+
27 (11.0%) D2
213 (86.9%)
Combined organ resection
34 (13.9%)
Tumor size (mm)
45.1±25.6
Proximal margin (mm)
54.0±23.9
Distal margin (mm)
54.4±36.4
Operative time (min)
298.9±87.3
Hospital day
16.1±13.9
Blood loss (ml)
75.6±79.0
Pathologic stage
Retrieved LNs
29.3±14.7 IA
70 (28.6%) IB
41 (16.7%)
IIA
20 (8.2%)
IIB
IIIA
24 (9.8%)
IIIB
25 (10.2%)
IIIC IV
18 (7.3%)
Advanced GC
169 (69.0%)
Here is the clinicopathologic characteristics. The mean age is 65 years old. 60% patients have comorbidities, and 72% of them have Charlson comorbidity index above patients had laparoscopic total gastrectomy. 69% belongs to advanced gastric cancer. By AJCC 7th edition, 35.5% have stage above three.

11. 30-day morbidity rate: 25.9% C-D ≧ 3 : 7.7%
Overall %
Early complication
Local
- Delayed gastric emptying 7
2.8
- Dumping 1
0.4
- Ileus 8
3.2
- Intestinal obstruction 2
0.8
- Chylous ascites 3
1.2
- Bleeding
- Intraabdominal abscess
- Anastomotic leakage
- Wound infection 4
1.6
Systemic
- Pneumonia 6 15
6.0
- Pleural effusion
2.4
- CRBSI
- Stroke
7.7 %
25.9
Late complication
- Adhesion related intestinal obstruction 9 11
4.4
- Internal herniation 5
- Anastomotic stricture
2.0
- Incisional hernia
- Acute cholecystitis
7.3 %
11.7
93 events in 79 patients
32.0
30-day morbidity rate: 25.9%
C-D ≧ 3 : 7.7%
To analyze adverse outcome, we list the events and severity by Clavien-Dindo classification here. Early complication is defined by events occurred within 30 days after surgery. Local refers to surgical site related complications. In summary, the 30-day morbidity rate is 25.9%, and only 7.7% of them are C-D classification above 3 that required intervention.

12. Risk factors for early complication
No complication n=188
Early complication n=57
univariate p value
Age
63.3±14.7
71.6±12.9
<0.001
Gender (M/F)
119/69 (63.3%/36.7%)
41/16 (71.9%/28.1%)
0.268
BMI
23.8±3.3
24.2±3.7
0.374
Preop albumin
3.9±0.5
3.7±0.6
0.006
ASA≧3
30 (16.0%)
17 (29.8%)
0.033
Prior abd. surgery
35 (18.6%)
12 (21.1%)
0.703
NACT
5 (2.7%)
3 (5.3%)
0.389
Procedure (LDG/LTG)
140/48 (74.5%/25.5%)
35/22 (61.4%/38.6%)
0.066
Extent of LN dissection (D2/Less than D2)
163/25 (86.7/13.3%)
50/7 (87.7%/12.3)
1.000
Combined organ resection
26 (13.8%)
8 (13.6%) 1
OP time
302.2±89.7
287.7±78.6
0.278
Blood loss
73.4±76.4
86.1±92.0
0.381
Tumor size
43.6±25.8
50.1±24.6
0.091
Proximal margin
54.3±24.1
53.0±23.4
0.791
Distal margin
52.7±34.5
59.8±42.2
0.201
Harvested LN
29.8±14.3
27.9±15.7
0.392
Pathologic advanced GC
123 (65.4%)
46 (80.7%)
The only predictor in logic regression model
(p=0.01)
In univariate analysis, early complications are associated with older age, lower preoperative albumin, ASA above 3, laparoscopic total gastrectomy, larger tumor size, and advanced disease. In multiple logistic regression analysis, age is the only predictor for adverse outcome.

13. Characteristics of aged vs. non-aged
Age < 70 (n=147)
Age ≧70 (n=98)
P value
Age
55.7±10.2
79.5±7.0
Gender (M:F)
89:58 (60.5%/39.5%)
71:27 (72.4%/27.6%)
0.057
BMI
24.0±3.5
23.6±3.3
0.669
Pre-op albumin (g/dL)
4.0±0.4
3.6±0.5
<0.001
Comorbidity
81 (55.1%)
18 (18.4%) 1
46 (31.3%)
44 (44.9%) ≧2
20 (13.6%)
36 (36.7%)
CCI
4.5±1.2
7.2±1.1
ASA score
56 (38.1%)
6 (6.1%) 2
80 (54.4%)
56 (57.1%)
≧ 3
11 (7.5%)
Prior abd. Surgery
29 (19.7%)
0.869
NACT
7 (4.8%)
1 (1.0%)
0.150
Advanced GC
100 (68.0%)
69 (70.4%)
0.778
Procedure
0.775
Distal gastrectomy
106 (72.1%)
Total gastrectomy
41 (27.9%)
29 (29.6%)
When we investigate the elderly subgroup, patients with age over 70 are associated with lower preoperative albumin, more comorbidities, and higher rate of ASA above 3.

14. Extent of LN dissection 0.441
Age < 70 (n=147)
Age ≧70 (n=98)
P value
Extent of LN dissection
0.441
Less than D2
17 (11.6%)
15 (15.3%) D2
130 (88.4%)
83 (84.7%)
Combined organ resection
18 (12.2%)
16 (16.3%)
0.451
Tumor size
42.6±23.6
48.9±28.1
0.057
Proximal margin
54.3±22.7
53.7±25.8
0.851
Distal margin
54.1±35.9
54.8±37.5
0.887
Blood loss
75.2±80.5
76.3±77.6
0.941
Operative time
312.1±93.5
279.2±73.4
0.004
Hospital day
13.5±8.2
20.0±18.9
<0.001
Retrieved LNs
30.9±14.3
27.0±15.0
0.044
Pathologic stage
0.297 IA
45 (30.6%)
25 (25.5%) IB
23 (15.6%)
18 (18.4%)
IIA
11 (7.5%)
9 (9.2%)
IIB
IIIA
10 (6.8%)
14 (14.3%)
IIIB
16 (10.9%)
IIIC
14 (9.5%)
6 (6.1%) IV
8 (8.2%)
Regarding the perioperative factors, elderly are associated with shorter operative time, slightly less retrieved LN, but longer hospital stay. There is no difference in the pathologic stage.

15. Complications of aged vs. non-aged
Age < 70 (n=147)
Age ≧70 (n=98)
P value
event %
Early complication 26
17.7 31
31.6
0.014
Local 20
13.6
0.584
Delayed gastric emptying 2
1.4 4
4.1
0.221
Dumping 1
0.7
1.0
Ileus 3
2.0 5
5.1
0.187
Intestinal obstruction
Chylous ascites
Bleeding
Intraabdominal abscess
3.4
3.1
Anastomotic leakage
0.518
Wound infection
Systemic 10
6.8 17
17.3
0.012
Pneumonia 13
13.3
<0.001
Pleural effusion
0.406
CRBSI
Stroke
Late complication 14
9.5 15
15.3
0.225
The complications from elderly are also compared to younger patients. Only pneumonia differ significantly. It is way higher than younger patients, up to 13.3%.

16. Elderly (≧70) at risk for pneumonia
No pneumonia n=85
Pneumonia n=13
P value
Age
78.8±6.6
83.8±7.9
0.016
≧85
18 (21.2%)
7 (53.8%)
0.019
Gender (M/F)
61/24(71.8%/28.2%)
10/3 (76.9%/23.1%) 1
Smoking
26 (30.6%)
5 (38.5%)
0.542
Hypertension
44 (51.8%)
9 (69.2%)
0.371 DM
27 (31.8%)
3 (23.1%)
0.749
COPD
1 (1.2%)
2 (15.4%)
0.045
CVA
4 (30.8%)
0.001
ASA≧3
0.013
Hx. of abd. surgery
(%)
BMI
23.7±3.4
22.9±2.4
0.441
Preop albumin
3.7±0.5
3.2±0.6
0.009
<3.0 g/dL
6 (7.1%)
0.026
NACT
0 (0%)
Here we try to identify the risk factors for pneumonia in elderly group. In addition to age, COPD, history of CVA, ASA above 3 and lower preoperative albumin were associated with pneumonia. However, history of CVA is the only predictor in the multiple logic regression model.
The only predictor in logic regression model

17. Combined organ resection 16 (18.8%) 0 (0%) 0.118
No pneumonia n=85
Pneumonia n=13
P value
Procedure (LDG/LTG)
62/23 (72.9%/27.1%)
7/6 (53.8%/46.2%)
0.196
Combined organ resection
16 (18.8%)
0 (0%)
0.118
OP time
281.9±76.6
260.2±42.9
0.342
Blood loss
77.22±78.9
70.0±75.8
0.848
Tumor size
49.0±28.4
48.6±26.7
0.965
Harvested LN
28.0±14.8
20.3±15.3
0.084
pAGC
58 (68.2%)
11 (84.6%)
0.334
Local complication
14 (16.5%)
2 (15.4%)
1.0
And neither the perioperative factors nor the cancer stage are associated with pneumonia.

18. 5-year Overall survival by stage
93.6%
87.3%
46.3%
In this cohort, the five-year overall survival by stage is 93.6% for stage I, 87.3% for stage II and 46.3% for stage III. That is comparable to those treated by open surgery.

19. 5-year disease-free survival by stage
96.3%
88.3%
51.8%
So is the five-year disease-free survival. We believe that it is better than the average survival data in Taiwan.

20. 5-year Overall Survival Elderly vs. adult
Log-rank test:
significance: 0.022
Here, we compare the overall survival of elderly to other adult patients. We did find significant shorter overall survival in patients over 70.

21. 5-year Disease-Free Survival Elderly vs. adult
Log-rank test:
significance: 0.955
However, they have equivalent disease-free survival to adult patients. So, LG for elderly patients is as effective as adult in disease control, though elderly may not be able to survive as long as adult because of their shorter life expectancy, probably related to their comorbidities and performance status.

22. Discussion Advanced age is associated with overall early morbidity.
However, elderly patients are at risk for pneumonia rather than surgical site complications
LG in elderly patients have similar oncologic benefit to adult
No different DFS
From this study, we had identified advanced age as a predictor for early morbidity. It is pneumonia rather than surgical site complications that accounts for the adverse outcome. Despite of the more complicated postoperative recovery, elderly patients may have same disease-free survival as adult.

23. The severity of the preoperative comorbidities and the patients’ physiological statuses were the main risk factors for early complication (pneumonia accounts for the majority)
What’s more important, the reason why elderly is associated with more pneumonia may not come from age itself, it is likely the severity of the preoperative comorbidities and the patient’s physiological statuses that contributes to the adverse outcome.

24. Metaanalysis Pan et al. Medicine (2018) 97:8
The result is in line with recent literature. One recent systematic review with meta-analysis about LG for elderly patients also shows significant higher overall postoperative complication for patients over 75; unsurprisingly, it comes from nonsurgical complications. In addition, risk for pneumonia increases significantly if age over 70.
Metaanalysis
Pan et al. Medicine (2018) 97:8

25. n=26 n=30 n=71 Metaanalysis Pan et al. Medicine (2018) 97:8
Only three studies in this review have survival data. Two showed no different survival data between elderly and adult. One showed shorter overall survival but no different disease-free survival, just like our result. This disconcordance may be explained by varied sample size and follow-up time between studies, that is, the prior two studies only with limited number of patients.
Metaanalysis
Pan et al. Medicine (2018) 97:8

26. Age ≧ 85 OP or Best supportive care (BSC) n=90
Elderly patients, especially for those aged over 85, have decreased life expectancies and decreased tolerance to stress. There is debate on surgery or best supportive care in this groups of patients with gastric cancer. Studies from Japan have demonstrated the survival benefits of surgery over best supportive care in patients over 85.
Endo. Int J Clin Oncol (2013) 18:1014–1019

27. Endo. Int J Clin Oncol (2013) 18:1014–1019
However, in subgroup analysis, male, patients aged over 90, and stage IA may not be able to benefit from surgery. Thus, the decision to perform surgery in these patients should be carefully made.
Endo. Int J Clin Oncol (2013) 18:1014–1019

28. LG VS OPEN gastrectomy for GC
Age ≧ 70
LG VS OPEN gastrectomy for GC
Another issue is the unclear safety profile of LG in elderly patients. One retrospective study from China compares LG to open surgery in elderly. The morbidity rates, either surgical site or systemic, are lower in the LG group. The 3-year cancer recurrence and mortality rate were similar in the two groups. So, regarding to gastric cancer surgery in elderly patients, LG could be an effective and even superior choice to open gastrectomy.
Li. Mol Clin Oncol 2: , 2014

29. Conclusion LG can be the standard care for GC
Comparable short- and long-term result in advanced stage and total gastrectomy
Elderly with multiple comorbidities are subject to postoperative pneumonia, especially those over 85
Optimize perioperative care
Shared decision making
LG can be the standard care for gastric cancer as it has comparable short- and long-term outcome, even in advanced stage or total gastrectomy. Elderly with multiple comorbidities are subject to postoperative pneumonia, especially those over 85. We should optimize perioperative care and have shared decision making with patients and family before surgery.