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Is laparoscopic colorectal surgery with continuation of antiplatelet therapy safe without increasing bleeding complications?

  • Kazuhiro Taguchi
  • Manabu ShimomuraEmail author
  • Hiroyuki Egi
  • Minoru Hattori
  • Shoichiro Mukai
  • Masatoshi Kochi
  • Haruki Sada
  • Yusuke Sumi
  • Ikki Nakashima
  • Shintaro Akabane
  • Koki Sato
  • Hideki Ohdan
Open Access
Original Article

Abstract

Purpose

The number of patients on antiplatelet therapy (APT) who need surgery is increasing; however, it is unclear whether APT should be continued for abdominal surgery, particularly laparoscopic colorectal surgery. We investigated the safety of continuing APT for patients undergoing laparoscopic colorectal surgery.

Methods

We collected retrospective data from 529 patients who underwent laparoscopic colorectal surgery at Hiroshima University between January, 2013 and December, 2018. We analyzed information related to APT. Thirty-six pairs were matched by the propensity score method between patients on APT (APT+) and those not on APT (APT−). We compared the surgical outcomes of both groups.

Results

Among 463 patients eligible for the study, 48 were on APT for cerebrovascular or cardiovascular disease, and 36 continued to take aspirin. In the case-matched comparison, the amount of intraoperative blood loss in the APT+ group was not significantly higher than that in the APT− group, and the incidences of bleeding complications, thromboembolic complications, and other complications were not significantly different between the groups.

Conclusion

In a case-matched comparison, continuation of aspirin during laparoscopic colorectal surgery did not increase perioperative complications. In laparoscopic colorectal surgery, continuation of aspirin is an acceptable strategy for patients with thromboembolic risk caused by interruption of APT.

Keywords

Laparoscopic colorectal surgery Antiplatelet therapy Surgical outcome 

Abbreviations

APT

Antiplatelet therapy

BMI

Body mass index

ASA

American Society of Anesthesiologists

PS

Performance status

VTE

Venous thromboembolism

PTE

Pulmonary thromboembolism

DVT

Deep-vein thrombosis

Introduction

Antiplatelet therapy (APT) is indicated for the prevention of primary and late thrombotic complications in patients with thrombotic diseases, such as cerebrovascular or cardiovascular disease. The number of patients with thrombotic disease is increasing in line with our aging population and deliberate antithrombotic management during abdominal surgical treatment is often required. Although interruption of APT is considered perioperatively to prevent excessive hemorrhagic risk, this can result in thrombotic events in patients with thrombotic diseases [1, 2]. Biondi-Zoccai reported that the withdrawal of aspirin treatment had ominous prognostic implications for patients at moderate-to-high risk for coronary artery disease and concluded that aspirin should be discontinued only when bleeding risk clearly overwhelms that of thrombotic events [3]. However, it remains unclear which situations should be given priority to interrupt APT. Although APT reduces the perioperative risk of thrombotic complications, it may increase the risk not only of worse intraoperative blood loss, but also of postoperative bleeding complications [4]. A meta-analysis revealed that aspirin continuation was not generally associated with higher mortality rates or poorer surgery outcomes, but it was associated with a 1.5-fold increase in perioperative blood loss [5]. Another meta-analysis suggested that APT at the time of non-cardiac surgery confers minimal bleeding risk with no difference in thrombotic complications [6]. Based on the findings of these investigations of intraoperative bleeding risk from APT, the safety profile for laparoscopic colorectal surgery while continuing APT remains unclear.

Laparoscopic colorectal surgery has become broadly accepted based on large multicenter randomized controlled trials, which show less blood loss [7, 8, 9, 10, 11]. However, it has not been extensively investigated whether APT affects the perioperative outcomes of patients undergoing laparoscopic colorectal surgery. Although some reports describe that laparoscopic colorectal surgery is safe for patients with APT [12, 13], it is still difficult to establish the appropriate indications for the continuation of APT because surgical invasiveness in laparoscopic colorectal surgery differs among surgical procedures and is influenced by oncological status such as tumor stage. We investigated the safety of APT for laparoscopic colorectal surgery with the continuation of APT, while considering variations in the surgical procedures.

Methods

Patients

We collected data retrospectively from 435 consecutive patients who underwent laparoscopic colorectal surgery for clinically diagnosed adenocarcinoma, at Hiroshima University Hospital between January 2013 and December 2018. We excluded 18 patients who had multiple cancers, 3 who underwent cholecystectomy simultaneously, 18 who underwent robotic system surgery, 4 who underwent total colectomy, and 23 who were on chronic oral anticoagulation therapy. For each of the total 463 patients, we obtained the following data: sex, age, body mass index (BMI), information on comorbidity including antiplatelet therapy, American Society of Anesthesiologists (ASA) class, performance status (PS) (World Health Organization), risk classification of venous thromboembolism (VTE) based on the Caprini score [14], tumor location, lymphadenectomy, surgical curability, tumor stage, and surgical outcome such as operative time, blood loss, intraoperative blood transfusion, open conversion, morbidity, and mortality. Morbidity included re-operation within 48 h, drop in hemoglobin level (> 2.0 g/dL), postoperative surgical site and other site bleeding, venous thromboembolism (VTE), cerebral or myocardial infarction, and other complications.

Perioperative management of antiplatelet therapy

We identified high thromboembolic risk patients comprehensively, and basically, following the guidelines of the Japan Gastroenterological Endoscopy Society (Fig. 1) [15]. APT was generally interrupted 1 week before surgery and restarted in the early postoperative period for low thromboembolic risk patients. In high thromboembolic risk patients, APT was continued in the form of aspirin alone or heparin bridging treatment. If patients were on chronic oral anticoagulation therapy, they were managed by the interruption of anticoagulation 5–7 days before surgery, bridging anticoagulation with unfractionated heparin, and early postoperative reinstitution. In patients on both APT and oral anticoagulation therapy, the perioperative management of APT was combined with that of anticoagulation therapy. We excluded patients who were managed by heparin bridging from analysis of the safety of APT, because heparin bridging would be an independent risk factor for postoperative bleeding complications [16]. We managed VTE as outlined in our previous reports [17, 18]. Mechanical prophylaxis against VTE, including the postoperative use of elastic stockings and intermittent pneumatic compression was routine for all patients. Pharmacological prophylaxis was administered to those at clinically high risk of VTE categorized by institutional risk classification, as low molecular weight heparin: enoxaparin sodium [via subcutaneous injection, twice a day, with enoxaparin sodium (2000 IU) for 1 week].
Fig. 1

High thromboembolic risk associated with interruption of an antiplatelet agent. This list was cited from the guidelines of the Japan Gastroenterological Endoscopy Society

Statistical analysis

Summary statistics were calculated using frequencies and proportions for categorical data and medians and ranges for continuous variables. Chi square tests were used for categorical data, and Mann–Whiney U tests and Kruskal–Wallis tests were used for continuous data.

Since there were differences in patient backgrounds and the style of operation among patients who continued to take aspirin (APT+) and those not on APT (APT−), we used a propensity score method to balance the observed covariates related to surgical invasiveness between the groups. Among patient factors, oncological factors and surgical factors, we chose the following as covariates which might affect surgical outcomes: sex, age, BMI, ASA-class, VTE risk classification, tumor location, lymphadenectomy, surgical curability and tumor stage. One-to-one propensity matching was performed using a caliper index of 0.20. Statistical analyses were performed using JMP13 for Windows (SAS Institute). P values of < 0.05 were considered significant.

Results

There were 463 patients in the final analysis, 48 of whom had been on APT for cerebrovascular or cardiovascular disease. Of those, 36 underwent laparoscopic colorectal surgery while continuing to take aspirin and 2 were managed by heparin bridging instead of continuation of APT. For the other 10 patients identified as being at low thromboembolic risk, APT was interrupted during the perioperative management (Fig. 2). The types of antiplatelet agents being used by these 48 patients were aspirin (n = 21), clopidogrel (n = 12), cilostazol (n = 6), ticlopidine (n = 1), a combination of aspirin and clopidogrel (n = 4), aspirin and cilostazol (n = 2), aspirin and ticlopidine (n = 1), and clopidogrel and cilostazol (n = 1) (Fig. 3). APT was interrupted in four patients who had been on aspirin, one who had been on clopidogrel, three who had been on cilostazol, one who had been on ticlopidine, and one who had been on a combination of aspirin and ticlopidine. Two of the patients who had been taking clopidogrel were managed by heparin bridging. Table 1 summarizes the patient characteristics and oncological status of patients who had been on APT vs. those who had not (N-APT). The proportion of men was significantly higher in the APT group (P = 0.0276). The median ages were 75 and 67 years in the APT group vs. the N-APT group, respectively (P < 0.0001). Both ASA-class and PS were poorer in the APT group (P < 0.0001, P = 0.0039, respectively). The proportion of patients with diabetes was significantly higher in the APT group (P = 0.0018). VTE risk classification was also significantly higher in the APT group (P = 0.0068). Oncological status was not significantly different between the groups. The patient characteristics and surgical outcomes of the patients who continued on APT (C-APT) vs. those with interrupted APT (I-APT) were not significantly different (Tables 2, 3, respectively). Next, we summarized the patient characteristics in the APT+ group vs. the APT− group. The median ages were 73 and 67 years, respectively (P < 0.0001), and the median BMI was 23.7 and 22.3, respectively (P = 0.0345). Both ASA-class and PS were poorer in the APT+ group (P < 0.0001, P = 0.0139, respectively). The proportion of patients with diabetes was significantly higher in the APT+ group (P = 0.0021). VTE risk classification was significantly higher in the APT+ group (P = 0.0018). For surgical factors, the distribution for the level of lymphadenectomy was significantly different in the two groups (P = 0.0212) (Table 4).
Fig. 2

Patient flow diagram

Fig. 3

Type of antiplatelet agents. Forty-eight patients used antiplatelet agents, which were interrupted in 10 patients (20.8%), while 2 patients (4.1%) were managed by heparin bridging during the perioperative period

Table 1

Patient characteristics and oncological status

 

Total (n = 463)

n (%)

APT (n = 48)

n (%)

N-APT (n = 415)

n (%)

P value

Sex

0.0276

 Male

281 (60.7)

36 (75.0)

245 (59.0)

 

 Female

182 (39.3)

12 (25.0)

170 (41.0)

 

Age (year old) [median (range)]

67 (22–94)

75 (52–90)

67 (69–94)

< 0.0001

BMI [median (range)]

22.4 (13.7–36.0)

23.5 (15.9–32.7)

22.4 (13.7–36.0)

0.2262

ASA-class

< 0.0001

 1

101 (21.8)

2 (4.2)

99 (23.9)

 

 2

337 (72.8)

34 (70.8)

303 (73.0))

 

 3

25 (5.4)

12 (25.0)

13 (3.1)

 

PS

0.0039

 0

407 (87.9)

36 (75.0)

371 (89.4)

 

 1

48 (10.4)

12 (25.0)

36 (8.7)

 

 2

8 (1.7)

0

8 (1.9)

 

Diabetes

0.0018

 Yes

388 (83.8)

16 (33.3)

59 (14.2)

 

 No

75 (16.2)

32 (66.7)

356 (85.8)

 

VTE risk classification

0.0058

 Low

67 (14.4)

1 (2.1)

66 (15.9)

 

 High

267 (57.7)

29 (60.4)

238 (57.4)

 

 Highest

129 (27.9)

18 (37.5)

111 (26.7)

 

Tumor location

0.2391

 Right

148 (32.0)

19 (39.6)

129 (31.1)

 

 Left

142 (30.7)

10 (20.8)

132 (31.8)

 

 Rectum

173 (37.3)

19 (39.6)

154 (37.1)

 

Stage

0.1282

 0

27 (5.8)

0

27 (6.5)

 

 I

225 (48.6)

25 (52.1)

200 (48.2)

 

 II

83 (18.0)

7 (14.6)

76 (18.3)

 

 III

101 (21.8)

12 (25.0)

89 (21.5)

 

 IV

27 (5.8)

4 (8.3)

23 (5.5)

 

BMI body mass index, ASA American Society of Anesthesiologists, PS performance status, VTE venous thromboembolism

Table 2

Patient characteristics in the continuing antiplatelet therapy (C-APT) and interrupted antiplatelet therapy (I-APT) groups

 

C-APT (n = 36)

n (%)

I-APT (n = 10)

n (%)

P value

Sex

0.7527

 Male

27 (75.0)

7 (70.0)

 

 Female

9 (25.0)

5 (33.3)

 

Age (year old) [median (range)]

73 (52–85)

78 (69–90)

0.2092

BMI [median (range)]

23.7 (17.1–32.7)

21.0 (15.9–28.7)

0.1874

ASA-class

0.5532

 1

2 (5.6)

0

 

 2

25 (69.4)

8 (80.0)

 

 3

9 (25.0)

2 (20.0)

 

PS

0.2773

 0

27 (75.0)

9 (90.0)

 

 1

9 (25.0)

1 (10.0)

 

 2

0

0

 

Diabetes

0.3206

 Yes

13 (36.1)

2 (20.0)

 

 No

23 (63.9)

8 (80.0)

 

VTE risk classification

0.1314

 Low

0

1 (10.0)

 

 High

22 (61.1)

7 (70.0)

 

 Highest

14 (38.9)

2 (20.0)

 

BMI body mass index, ASA American Society of Anesthesiologists, PS performance status, VTE venous thromboembolism

Table 3

Surgical outcomes of the continuing antiplatelet therapy (C-APT) and interrupted antiplatelet therapy (I-APT) groups

 

C-APT (n = 36)

n (%)

I-APT (n = 10)

n (%)

P value

Operative time (min) [median (range)]

305 (69–627)

285 (158–372)

0.4243

Blood loss (ml) [median (range)]

57 (5–483)

16 (5–240)

0.0567

Intraoperative blood transfusion

 Yes

0

0

 

 No

36 (100)

10 (100)

 

Open conversion

0.3160

 Yes

2 (5.6)

0

 

 No

34 (94.4)

10 (100)

 

Re-operation within 48 h

 Yes

0

0

 

 No

36 (100)

10 (100)

 

Hb drop (> 2.0)

0.1508

 Yes

4 (11.1)

0

 

 No

32 (88.9)

10 (100)

 

Postoperative surgical sight bleeding

 Yes

0

0

 

 No

36 (100)

10 (100)

 

Postoperative other sight bleeding

 Yes

0

0

 

 No

36 (100)

10 (100)

 

VTE

0.4811

 Yes

1 (2.8)

0

 

 No

35 (97.2)

10 (100)

 

Cerebral or myocardial infarction

 Yes

0

0

 

 No

36 (100)

10 (100)

 

Hb hemoglobin, VTE venous thromboembolism

Table 4

Patient characteristics and surgical factors overall and after propensity score matching in the antiplatelet therapy (APT+) vs. no antiplatelet therapy (APT−) groups

 

APT+ (n = 36)

n (%)

APT−

Overall (n = 425) n (%)

P value

After matching (n = 36)

n (%)

P value

Sex

  

0.0569

 

0.7891

 Male

27 (75.0)

252 (59.3)

 

26 (72.2)

 

 Female

9 (25.0)

173 (40.7)

 

10 (27.8)

 

Age (year old) [median (range)]

73 (52–85)

67 (22–94)

< 0.0001

78 (57–90)

0.4773

BMI [median (range)]

23.7 (17.1–32.7)

22.3 (13.7–36.0)

0.0345

23.6 (15.9–30.1)

0.7525

ASA-class

  

< 0.0001

 

0.8780

 1

2 (5.6)

99 (23.3)

 

3 (8.3)

 

 2

25 (69.4)

311 (73.2)

 

25 (69.4)

 

 3

9 (25.0)

15 (3.5)

 

8 (22.2)

 

VTE risk classification

  

0.0018

 

0.4749

 Moderate

0

67 (15.8)

 

0

 

 High

22 (61.1)

245 (57.6)

 

19 (52.8)

 

 Highest

14 (38.9)

113 (26.6)

 

17 (47.2)

 

Tumor location

  

0.2834

 

0.9494

 Right

14 (38.9)

134 (31.5)

 

13 (36.1)

 

 Left

7 (19.4)

134 (31.5)

 

8 (22.2)

 

 Rectum

15 (41.7)

157 (37.0)

 

15 (41.7)

 

Lymphadenectomy

  

0.0212

 

1.0000

 D2

27 (75.0)

237 (55.8)

 

27 (75.0)

 

 D3

9 (25.0)

188 (44.2)

 

9 (25.0)

 

Surgical curability

  

0.9213

 

0.5517

 R0

34 (94.4)

401 (94.4)

 

35 (97.2)

 

 R1

0

1 (0.2)

 

0

 

 R2

2 (5.6)

23 (5.4)

 

1 (2.8)

 

Stage

  

0.1713

 

0.8632

 0

0

27 (6.3)

 

0

 

 I

21 (58.3)

203 (47.8)

 

24 (66.7)

 

 II

4 (11.1)

78 (18.3)

 

3 (8.3)

 

 III

9 (25.0)

92 (21.7)

 

8 (22.2)

 

 IV

2 (5.6)

25 (5.9)

 

1 (2.8)

 

BMI body mass index, ASA American Society of Anesthesiologists, VTE venous thromboembolism

Since APT may increase the risks related to perioperative bleeding complications, we compared the surgical short outcomes between the APT+ and APT− groups. In this cohort, patient background and surgical invasiveness, including the level of lymphadenectomy, differed between the groups. We selected 36 matched pairs from among these patients by the propensity score method and found no significant difference in any patient characteristics or surgical factor between the groups after matching (Table 4). In these matched pairs, the intraoperative blood loss in the APT+ group was not significantly higher than that in the APT− group (median, 57 and 54 ml, respectively, P = 0.5026). There were no significant differences in bleeding complications, thromboembolic complications, and other complications between the APT+ and APT− groups (Table 5).
Table 5

Surgical outcomes of the antiplatelet therapy (APT+) and no antiplatelet therapy (APT−) groups

 

APT+ (n = 36)

n (%)

APT− (n = 36)

n (%)

P value

Operative time (min) [median (range)]

305 (69–627)

296 (158–539)

0.8437

Blood loss (ml) [median (range)]

57 (5–483)

54 (7–359)

0.5026

Intraoperative blood transfusion

  

 Yes

0

0

 

 No

36 (100)

36 (100)

 

Open conversion

  

1.0000

 Yes

2 (5.6)

2 (5.6)

 

 No

34 (94.4)

34 (94.4)

 

Re-operation within 48 h

  

 Yes

0

0

 

 No

36 (100)

36 (100)

 

Hb drop (> 2.0)

  

0.6903

 Yes

4 (11.1)

3 (8.3)

 

 No

32 (88.9)

33 (91.7)

 

Postoperative surgical sight bleeding

  

0.2367

 Yes

0

1 (2.8)

 

 No

36 (100)

35 (97.2)

 

Postoperative other sight bleeding

  

 Yes

0

0

 

 No

36 (100)

36 (100)

 

VTE

  

0.2367

 Yes

1 (2.8)

0

 

 No

35 (97.2)

36 (100)

 

Cerebral or myocardial infarction

  

 Yes

0

0

 

 No

36 (100)

36 (100)

 

Other complications (G2)

  

0.5263

 Yes

7 (19.4)

5 (13.9)

 

 No

29 (80.6)

31 (86.1)

 

Other complications (> G3)

  

0.3231

 Yes

7 (19.4)

4 (11.1)

 

 No

29 (80.6)

32 (88.9)

 

Mortality (within 1 month)

  

 Yes

0

0

 

 No

36 (100)

36 (100)

 

Period of hospital stay (day) [median (range)]

12 (7–126)

11 (7–91)

0.1586

Hb hemoglobin, VTE venous thromboembolism

Discussion

We investigated the safety of patients continuing APT when undergoing laparoscopic colorectal surgery. This study demonstrated that continuation of APT during laparoscopic colorectal surgery did not increase perioperative complications in a case-matched comparison.

Antithrombotic management and antibleeding management are contradictory strategies in surgical treatment. For patients on continuing antiplatelet agents, perioperative antithrombotic management during abdominal surgery is challenging due to the increased risk of perioperative bleeding and thromboembolism. When these patients undergo major abdominal surgery, interruption of APT is conventionally recommended to prevent hemorrhagic occurrence, but it has recently been considered that thromboembolic complications could be more critical than bleeding complications. Major surgery, particularly that involving the abdomen, pelvis, and lower extremities, is an important trigger of a thrombophilic state [19]. This state is supposedly further aggravated by the proinflammatory and prothrombotic effect of surgical invasion during the perioperative period. Considering this context, the optimal management of patients with APT during major abdominal surgery is still undefined. Conversely, the Japan Gastroenterological Endoscopy Society guidelines for the management of patients on antithrombotic therapy state that its continuation is indicated during a gastroenterological endoscopic procedure. We applied this guideline to patients who underwent laparoscopic colorectal surgery and high thromboembolic risk patients who continued on a single antiplatelet agent, usually aspirin.

First, to evaluate whether APT should be interrupted during laparoscopic colorectal surgery in the clinical setting, we compared surgical outcomes between patients who continued APT and those whose APT was interrupted. In this study, no thromboembolic complications, including cerebral and myocardial infarction, occurred as a result of the interruption of APT, but it was difficult to recommend interruption of APT definitively because of the small number of cases. Therefore, we focused on investigating the safety of APT through a comparison with patients not on APT.

In laparoscopic colorectal surgery, various surgical factors determine invasiveness, such as the level of lymphadenectomy. Difficulty and invasiveness differ among procedures for colorectal surgery and are basically defined by tumor location. As such, these factors affect surgical outcomes, including intraoperative blood loss and postoperative bleeding complications. While it is important to consider such variations in the analysis of surgical outcomes, the high thromboembolic risk patients in this study potentially underwent less-invasive surgery to prioritize surgical safety because such patients generally have comorbidities, resulting in poor surgical outcomes. Another study considered that the level of lymphadenectomy was reduced in elderly patients, likely to have comorbidities causing perioperative complications [20]. Those authors performed a propensity score-matching analysis using not only patient background but also surgical invasiveness, including the level of lymphadenectomy [20]. In our retrospective study, patients in the APT+ group possibly underwent less-invasive surgery than those in the APT− group; therefore, we performed a propensity score method to balance surgical invasiveness. This may be the first report to include a surgical invasiveness-matched comparison to assess antithrombotic management during laparoscopic colorectal surgery. We evaluated outcomes without the different distributions of various surgical factors to arrive at a more precise validation of APT safety.

To evaluate the safety of laparoscopic colorectal surgery while continuing APT, we also compared surgical short-term outcomes such as the amount of intraoperative blood loss, intraoperative blood transfusion, other morbidities, and mortality. It has been reported that blood loss during surgery for colon cancer influences long-term survival [21], although the permissible blood loss without the risk of other outcomes is unclear. In this comparison, the amount of blood loss was not significantly different between the APT+ and APT− groups. Moreover, in these pairs, there were no cases of critical damage caused by intraoperative bleeding and no significant differences in other complications between the groups. These results suggest that laparoscopic colorectal surgery can be performed safely on patients continuing to take APT.

This study had some limitations. First, it was a retrospective cohort study, so there was bias in the management of APT. APT was continued for patients at high thromboembolic risk as identified by guidelines, but decisions were made comprehensively about whether to continue APT. Patients who were given heparin instead of APT during the perioperative period were excluded from the analysis because it was unclear whether this alternative treatment would affect surgical outcomes. Management to prevent VTE based on the risk classification differed among patients and this might also affect bleeding and thromboembolic complications. Second, there was bias in the selection of operation style, which we resolved between the APT+ and APT− groups using the propensity score method, although left-hemicolectomy, intersphincteric resection, and Hartmann operation were not included in this analysis. Third, comparison between the APT+ and APT− groups was performed on a small sample size due to the small number of patients on APT. The incidence of bleeding complications was generally less than 5% [22]. Since the frequency of symptomatic pulmonary thromboembolism has been reported as 0.5–1.6% [19, 23, 24], it was difficult to evaluate such differences in this small sample size. In this study, there were no bleeding complications caused by the continuation of APT.

Conclusion

In a case-matched comparison, the continuation of aspirin did not increase perioperative complications. In laparoscopic colorectal surgery, continuation of aspirin is an acceptable treatment strategy for patients at thromboembolic risk caused by an interruption of APT.

Notes

Author contributions

KT, MS, HE, and HO conceived and designed the report. SM, MK, HS, YS, IN, SA, and KS participated in the acquisition of data. KT, MS, HE, and HO analyzed and interpreted the data. MS, HE, and MH drafted the manuscript. MH helped with statistical analysis. MS, HE, and HO coordinated and critically revised the report. All the authors read and approved the final manuscript.

Compliance with ethical standards

Conflict of interest

We have no conflicts of interest to declare.

Ethical approval

This work was approved by the ethical committee of Hiroshima University (number E-339).

References

  1. 1.
    Sibon I, Orgogozo JM. Antiplatelet drug discontinuation is a risk factor for ischemic stroke. Neurology. 2004;62(7):1187–9.Google Scholar
  2. 2.
    Maulaz AB, Bezerra DC, Michel P, Bogousslavsky J. Effect of discontinuing aspirin therapy on the risk of brain ischemic stroke. Arch Neurol. 2005;62(8):1217–20.  https://doi.org/10.1001/archneur.62.8.1217.Google Scholar
  3. 3.
    Biondi-Zoccai GG, Lotrionte M, Agostoni P, Abbate A, Fusaro M, Burzotta F, et al. A systematic review and meta-analysis on the hazards of discontinuing or not adhering to aspirin among 50,279 patients at risk for coronary artery disease. Eur Heart J. 2006;27(22):2667–74.  https://doi.org/10.1093/eurheartj/ehl334.Google Scholar
  4. 4.
    Mita K, Ito H, Murabayashi R, Sueyoshi K, Asakawa H, Nabetani M, et al. Postoperative bleeding complications after gastric cancer surgery in patients receiving anticoagulation and/or antiplatelet agents. Ann Surg Oncol. 2012;19(12):3745–52.  https://doi.org/10.1245/s10434-012-2500-6.Google Scholar
  5. 5.
    Burger W, Chemnitius JM, Kneissl GD, Rucker G. Low-dose aspirin for secondary cardiovascular prevention—cardiovascular risks after its perioperative withdrawal versus bleeding risks with its continuation—review and meta-analysis. J Intern Med. 2005;257(5):399–414.  https://doi.org/10.1111/j.1365-2796.2005.01477.x.Google Scholar
  6. 6.
    Columbo JA, Lambour AJ, Sundling RA, Chauhan NB, Bessen SY, Linshaw DL, et al. A meta-analysis of the impact of aspirin, clopidogrel, and dual antiplatelet therapy on bleeding complications in noncardiac surgery. Ann Surg. 2018;267(1):1–10.  https://doi.org/10.1097/SLA.0000000000002279.Google Scholar
  7. 7.
    Lacy AM, Garcia-Valdecasas JC, Delgado S, Castells A, Taura P, Pique JM, et al. Laparoscopy-assisted colectomy versus open colectomy for treatment of non-metastatic colon cancer: a randomised trial. Lancet. 2002;359(9325):2224–9.  https://doi.org/10.1016/S0140-6736(02)09290-5.Google Scholar
  8. 8.
    Veldkamp R, Kuhry E, Hop WC, Jeekel J, Kazemier G, Bonjer HJ, et al. Laparoscopic surgery versus open surgery for colon cancer: short-term outcomes of a randomised trial. Lancet Oncol. 2005;6(7):477–84.  https://doi.org/10.1016/S1470-2045(05)70221-7.Google Scholar
  9. 9.
    Hewett PJ, Allardyce RA, Bagshaw PF, Frampton CM, Frizelle FA, Rieger NA, et al. Short-term outcomes of the Australasian randomized clinical study comparing laparoscopic and conventional open surgical treatments for colon cancer: the ALCCaS trial. Ann Surg. 2008;248(5):728–38.  https://doi.org/10.1097/SLA.0b013e31818b7595.Google Scholar
  10. 10.
    van der Pas MH, Haglind E, Cuesta MA, Furst A, Lacy AM, Hop WC, et al. Laparoscopic versus open surgery for rectal cancer (COLOR II): short-term outcomes of a randomised, phase 3 trial. Lancet Oncol. 2013;14(3):210–8.  https://doi.org/10.1016/S1470-2045(13)70016-0.Google Scholar
  11. 11.
    Yamamoto S, Inomata M, Katayama H, Mizusawa J, Etoh T, Konishi F, et al. Short-term surgical outcomes from a randomized controlled trial to evaluate laparoscopic and open D3 dissection for stage II/III colon cancer: Japan Clinical Oncology Group Study JCOG 0404. Ann Surg. 2014;260(1):23–30.  https://doi.org/10.1097/SLA.0000000000000499.Google Scholar
  12. 12.
    Fujikawa T, Tanaka A, Abe T, Yoshimoto Y, Tada S, Maekawa H, et al. Does antiplatelet therapy affect outcomes of patients receiving abdominal laparoscopic surgery? Lessons from more than 1000 laparoscopic operations in a single tertiary referral hospital. J Am Coll Surg. 2013;217(6):1044–53.  https://doi.org/10.1016/j.jamcollsurg.2013.08.005.Google Scholar
  13. 13.
    Ono K, Idani H, Hidaka H, Kusudo K, Koyama Y, Taguchi S. Effect of aspirin continuation on blood loss and postoperative morbidity in patients undergoing laparoscopic cholecystectomy or colorectal cancer resection. Surg Laparosc Endosc Percutaneous Tech. 2013;23(1):97–100.  https://doi.org/10.1097/SLE.0b013e318278cdf8.Google Scholar
  14. 14.
    Bahl V, Hu HM, Henke PK, Wakefield TW, Campbell DA Jr, Caprini JA. A validation study of a retrospective venous thromboembolism risk scoring method. Ann Surg. 2010;251(2):344–50.  https://doi.org/10.1097/SLA.0b013e3181b7fca6.Google Scholar
  15. 15.
    Fujimoto K, Fujishiro M, Kato M, Higuchi K, Iwakiri R, Sakamoto C, et al. Guidelines for gastroenterological endoscopy in patients undergoing antithrombotic treatment. Dig Endosc. 2014;26(1):1–14.  https://doi.org/10.1111/den.12183.Google Scholar
  16. 16.
    Fujikawa T, Tanaka A, Abe T, Yoshimoto Y, Tada S, Maekawa H. Effect of antiplatelet therapy on patients undergoing gastroenterological surgery: thromboembolic risks versus bleeding risks during its perioperative withdrawal. World J Surg. 2015;39(1):139–49.  https://doi.org/10.1007/s00268-014-2760-3.Google Scholar
  17. 17.
    Shimomura M, Kochi M, Hinoi T, Egi H, Adachi T, Kobayashi T, et al. Clinical significance of pharmacological prophylaxis based on the original risk classification of venous thromboembolism after lower abdominal surgery. Hiroshima J Med Sci. 2016;65(3–4):53–9.Google Scholar
  18. 18.
    Kochi M, Shimomura M, Hinoi T, Egi H, Tanabe K, Ishizaki Y, et al. possible role of soluble fibrin monomer complex after gastroenterological surgery. World J Gastroenterol. 2017;23(12):2209–16.  https://doi.org/10.3748/wjg.v23.i12.2209.Google Scholar
  19. 19.
    Geerts WH, Heit JA, Clagett GP, Pineo GF, Colwell CW, Anderson FA Jr, et al. Prevention of venous thromboembolism. Chest. 2001;119(1 Suppl):132S–75S.Google Scholar
  20. 20.
    Shiga M, Maeda H, Oba K, Okamoto K, Namikawa T, Fujisawa K, et al. Safety of laparoscopic surgery for colorectal cancer in patients over 80 years old: a propensity score matching study. Surg Today. 2017;47(8):951–8.  https://doi.org/10.1007/s00595-017-1470-5.Google Scholar
  21. 21.
    Morner ME, Gunnarsson U, Jestin P, Svanfeldt M. The importance of blood loss during colon cancer surgery for long-term survival: an epidemiological study based on a population based register. Ann Surg. 2012;255(6):1126–8.  https://doi.org/10.1097/SLA.0b013e3182512df0.Google Scholar
  22. 22.
    Gould MK, Garcia DA, Wren SM, Karanicolas PJ, Arcelus JI, Heit JA, et al. Prevention of VTE in nonorthopedic surgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e227S–77S.  https://doi.org/10.1378/chest.11-2297.Google Scholar
  23. 23.
    Sakon M, Maehara Y, Yoshikawa H, Akaza H. Incidence of venous thromboembolism following major abdominal surgery: a multi-center, prospective epidemiological study in Japan. J Thromb Haemost. 2006;4(3):581–6.  https://doi.org/10.1111/j.1538-7836.2006.01786.x.Google Scholar
  24. 24.
    Mismetti P, Laporte S, Darmon JY, Buchmuller A, Decousus H. Meta-analysis of low molecular weight heparin in the prevention of venous thromboembolism in general surgery. Br J Surg. 2001;88(7):913–30.  https://doi.org/10.1046/j.0007-1323.2001.01800.x.Google Scholar

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© The Author(s) 2019

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Authors and Affiliations

  • Kazuhiro Taguchi
    • 1
    • 2
  • Manabu Shimomura
    • 3
    Email author
  • Hiroyuki Egi
    • 1
  • Minoru Hattori
    • 4
  • Shoichiro Mukai
    • 1
  • Masatoshi Kochi
    • 1
  • Haruki Sada
    • 1
  • Yusuke Sumi
    • 1
  • Ikki Nakashima
    • 1
  • Shintaro Akabane
    • 1
  • Koki Sato
    • 1
  • Hideki Ohdan
    • 1
  1. 1.Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health SciencesHiroshima UniversityHiroshimaJapan
  2. 2.Institute for Clinical Research, National Hospital OrganizationKure Medical Center and Chugoku Cancer CenterKureJapan
  3. 3.Department of SurgeryHiroshima City Asa Citizens HospitalHiroshimaJapan
  4. 4.Advanced Medical Skills Training Center, Institute of Biomedical and Health SciencesHiroshima UniversityHiroshimaJapan

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