- Email: [email protected]
Incidence and predictors of deep venous thrombosis after abdominal oncologic surgery: Prospective Doppler ultrasound screening
j o u r n a l o f s u r g i c a l r e s e a r c h 1 7 8 ( 2 0 1 2 ) 6 5 7 e6 6 1
Available online at www.sciencedirect.com
journal homepage: www.JournalofSurgicalResearch.com
Incidence and predictors of deep venous thrombosis after abdominal oncologic surgery: Prospective Doppler ultrasound screening Keishi Sugimachi, MD, PhD,a,b,* Hirotada Tajiri, MD,a Nao Kinjo, MD, PhD,a Masahiko Ikebe, MD, PhD,a Huanlin Wang, MD,a Kiyoshi Tanaka, MD, PhD,c Junko Tanaka, MD, PhD,a Shuichi Tsukamoto, MD, PhD,a Shinsuke Mii, MD, PhD,c and Hidefumi Higashi, MD, PhDa a
Department of Surgery, Steel Memorial Yawata Hospital, Kitakyushu, Japan Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan c Department of Vascular Surgery, Steel Memorial Yawata Hospital, Kitakyushu, Japan b
article info
abstract
Article history:
Background: Venous thromboembolism is a relatively rare but serious complication of
Received 6 March 2012
abdominal surgery. This study evaluated the incidence and risk factors for the develop-
Received in revised form
ment of deep venous thrombosis (DVT) after abdominal oncologic surgery using color
21 May 2012
Doppler ultrasonography (DUS).
Accepted 1 June 2012
Methods: This study enrolled 132 consecutive patients who underwent elective abdominal
Available online 20 June 2012
surgery for malignant tumors. Patients were investigated for DVT using DUS on postoperative day 7 2. Correlations between the incidence of DVT and clinicopathologic
Keywords:
parameters and the postoperative course were evaluated.
Deep venous thrombosis
Results: DVT was found in 15 patients (11.4%) using DUS. Clinically evident venous
Abdominal surgery
thromboembolism, including pulmonary embolism, was not found in these patients. The
Doppler ultrasonography
incidence of DVT was significantly higher in females (P ¼ 0.002), patients with a lower body mass index (P ¼ 0.008), and patients with a higher preoperative D-dimer level (P < 0.0001). Conclusions: DUS is noninvasive and is useful for postoperative DVT screening. Thromboprophylaxis is essential in high-risk patients who have undergone abdominal oncologic surgery. ª 2012 Elsevier Inc. All rights reserved.
1.
Introduction
The overall incidence of venous thromboembolism (VTE) in patients who have undergone general surgery without prophylactic treatment is reported to be approximately 29% in
the Western countries [1] and 24% in Japan [2]. VTE, presenting as deep venous thrombosis (DVT) or pulmonary embolism, may be a serious life-threatening complication after major abdominal surgery [1]. Major abdominal surgery promotes a hypercoagulable state that increases the expected risk of
* Corresponding author. Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Tsurumi, Beppu 874-0838, Japan. Tel.: þ81 977 27 1650; fax: þ81 977 27 1651. E-mail address: [email protected] (K. Sugimachi). 0022-4804/$ e see front matter ª 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jss.2012.06.002
658
j o u r n a l o f s u r g i c a l r e s e a r c h 1 7 8 ( 2 0 1 2 ) 6 5 7 e6 6 1
VTE associated with immobilization [3]. Patients with active malignancy also have a higher risk of developing DVT in the perioperative period [4]. In the eighth edition of the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines, administration of postoperative lowemolecular-weight heparin, low-dose unfractionated heparin, or fondaparinux for VTE prophylaxis after high-risk major abdominal surgery has a grade 1A indication [5]. However, the increased risk of postoperative bleeding, especially the risk of epidural hematoma associated with epidural anesthesia, is a serious potential consequence of using pharmacologic prophylaxis for VTE [6]. To establish effective and safe strategies for prophylaxis, more accurate information on the incidence of DVT in patients who have undergone oncologic surgery is needed. To our knowledge, this is the first study assessing the incidence of DVT after abdominal oncologic surgery using Doppler ultrasonography (DUS). The objective of this study was to evaluate the incidence and predictors of DVT after abdominal oncologic surgery.
2.
Materials and methods
2.1.
Patients
From January to December 2011, 132 consecutive patients who underwent elective abdominal oncologic surgery at our institute were enrolled in the study preoperatively. There were no exclusion criteria, but the patients who could not be performed postoperative DUS were excluded. Data from all these patients were analyzed. This prospective observational study was approved by the Ethics and Indications Committee of Steel Memorial Yawata Hospital. Patient data are summarized in Table 1. The median age of the patients was 71 y (range, 42e94 y).
2.2.
Operative procedure and postoperative care
In the present study, there was no intention to select the method of DVT prophylaxis. The intermittent sequential pneumatic compression device (Kendall SCD Response Sequential Compression System; Covidien Japan, Tokyo, Japan) and compression stockings were used in 130 (98.5%) of 132 patients during the operation and until the patients were ambulatory postoperatively. Pharmacologic prophylaxis was administered to 16 (12.1%) of 132 patients. Fondaparinux (Xa inhibitor) was used in 15 patients, and enoxaparin was used in one patient. Pharmacologic prophylaxis was started after the epidural catheter was removed in all patients. Patients were encouraged to ambulate postoperatively by the advanced physical therapists.
2.3.
Table 1 e Characteristics of the 132 patients in this study. Characteristics Age (y) Sex Male Female BMI (kg/m2) Diabetes Hypertension VTE history Central venous catheter Preoperative chemotherapy Indication for surgery Esophageal cancer Gastric cancer Colorectal cancer Hepatic cancer Pancreaticobiliary cancer Operative position Supine Lithotomy Lateral Operation time (min) Blood loss (g) Laparoscopic surgery Anesthesia General General þ epidural Mechanical DVT prophylaxis Pharmacologic DVT prophylaxis
Mean SD (range)/n (%) 70.7 9.6 (42e94) 91 (69) 41 (31) 22.5 3.5 (14.5e8.1) 27 (20) 67 (51) 1 (1) 22 (17) 20 (15) 6 26 45 48 7 80 33 19 234 138 241 359 33 45 87 131 16
(5) (20) (34) (36) (5) (61) (25) (14) (35e690) (10e2050) (25) (34) (66) (99) (12)
SD ¼ standard deviation.
femoral veins were imaged. The patient was then placed in a sitting position, and the popliteal vein in the popliteal fossa, soleus, peroneal, and tibial veins were imaged. The veins were imaged in gray scale to detect thrombosis and respiratory movement, and compressibility was assessed in the sagittal and coronal planes. Vascular flow was assessed by color Doppler analysis. The images were recorded using a 7.5 MHz linear transducer (LOGIQ S8; GE Healthcare UK Ltd, Buckinghamshire, England). The results of DUS were classified as abnormal if thrombosis was detected or if the venous segments imaged were not compressible (Fig. 1) [7].
2.4.
Statistical analysis
All statistical analyses were performed using JMP 8.0 software (SAS Institute Inc, Cary, NC). All variables were expressed as the mean standard deviation. Continuous variables were compared using the ManneWhitney U test. Categorical data were compared using the c2 test. Logistic regression analysis was performed to identify the independent predictors of DVT. A P value of <0.05 was regarded as statistically significant.
Ultrasonographic diagnosis of DVT
Patients were investigated for DVT using DUS on postoperative day 7 2. DUS was performed by licensed clinical vascular technologists (Japanese Society of Vascular Surgery, Japanese College of Angiology, and Japanese Society of Phlebology). First, each patient was scanned in the supine position. The common femoral, superficial femoral, and deep
3.
Results
3.1.
Incidence of DVT
DVT was detected in 15 patients (11.4%) by DUS. No patients showed any clinical symptoms related to DVT. The location of
659
j o u r n a l o f s u r g i c a l r e s e a r c h 1 7 8 ( 2 0 1 2 ) 6 5 7 e6 6 1
Table 2 e Relationships between clinicopathologic parameters and DVT after abdominal oncologic surgery.
Fig. 1 e Ultrasonographic images of DVT in the soleus vein. (A) Sagittal view and (B) coronal view. (Color version of figure is available online.)
DVT was the left soleus vein in nine cases (60%), bilateral soleus veins in two cases (13%), left peroneal vein in two cases (13%), left femoral vein in one case (7%), and bilateral external iliac veins in one case (7%). Therefore, DVT occurred in the left limb in 12 cases (80%) and in a distal vein in 13 cases (87%). All the 15 patients had received mechanical prophylaxis since the start of their operation, and pharmacologic prophylaxis had been initiated before DVT was diagnosed in two cases. After DVT was diagnosed, these patients underwent anticoagulant therapy for up to 6 mo. There were no cases of pulmonary embolism during the follow-up period.
3.2.
Risk factors for DVT
Table 2 shows the clinicopathologic parameters related to the incidence of DVT after abdominal oncologic surgery. Ten (24%) of 41 female patients developed DVT, which was significantly higher than the proportion of male patients (5.5%) who developed DVT. The average body mass index (BMI) of patients with DVT was significantly lower than that of patients without DVT. Patients who underwent gastrointestinal (GI) surgery had a significantly higher incidence of DVT than those who underwent hepatobiliaryepancreatic (HBP) surgery. Preoperative D-dimer levels in patients with DVT were significantly higher than those in patients without DVT.
Parameters
VTE () (n ¼ 117)
VTE (þ) (n ¼ 15)
P value
Age (y) Sex Male Female BMI (kg/m2) Diabetes (%) Hypertension (%) Central venous catheter (%) Preoperative chemotherapy (%) Preoperative DD (mg/mL) Type of surgery GI HBP Operative position Supine Lithotomy Lateral Operation time (min) Blood loss (g) Blood transfusion Laparoscopic surgery Epidural anesthesia Pharmacologic prophylaxis Postoperative DD (POD 1) (mg/mL) Postoperative DD (POD 7) (mg/mL) Ambulation (d) Complication (þ)
70.2 0.9
73.9 2.5
0.913
86 31 22.8 0.3 25 (21.4) 59 (50.4) 20 (17.1) 17 (14.5)
5 10 20.5 0.9 2 (13.3) 8 (53.3) 2 (13.3) 3 (20.0)
0.002
1.7 0.4
7.1 1.1
65 (49.2) 52 (39.4)
13 (9.9) 2 (1.5)
72 (54.5) 27 (20.5) 18 (13.6) 234 13 259 33 24 (20.5) 27 (23.1) 77 (65.8) 14 (12.0) 7.1 0.6
8 (6.1) 6 (4.5) 1 (0.8) 229 36 101 92 3 (20.0) 6 (40.0) 10 (66.7) 2 (13.3) 10.6 1.9
0.891 0.109 0.963 0.173 0.948 0.880 0.076
10.8 0.9
14.3 2.6
0.219
1.9 0.3 23 (19.7)
1.9 0.7 6 (40.0)
0.996 0.092
0.016 0.448 0.832 0.701 0.591 <0.0001 0.014
0.312
DD ¼ D-dimer; POD ¼ postoperative day; GI ¼ gastrointestinal; HBP ¼ hepatobiliary-pancreatic. Data are presented as mean standard deviation or as n (%).
Postoperative D-dimer levels in patients with DVT tended to be higher than those in patients without DVT, but this difference was not statistically significant (P ¼ 0.07). Multivariate analysis showed that female gender, BMI <22 kg/m2, and preoperative D-dimer >3 mg/mL were independent predictors for the development of DVT after surgery (Table 3).
4.
Discussion
This study investigated the incidence of DVT in patients who had undergone abdominal oncologic surgery. Patients with cancer are reported to have a higher risk of VTE than those without cancer [8]. Moreover, thromboprophylaxis might be
Table 3 e Multivariate analysis predicting the incidence of DVT after abdominal oncologic surgery. Factors Sex: female Preoperative DD: >3 mg/mL BMI: <22 kg/m2
Odds ratio
95% CI
P value
2.83 2.80 3.62
1.34e6.74 1.17e7.25 1.37e16.8
0.009 0.023 0.029
CI ¼ confidence interval; DD ¼ D-dimer.
660
j o u r n a l o f s u r g i c a l r e s e a r c h 1 7 8 ( 2 0 1 2 ) 6 5 7 e6 6 1
less effective, and the risk of major bleeding might be higher, in patients with cancer than those without cancer [9]. It is therefore necessary to assess the risk factors for DVT in patients with cancer to establish an effective and safe thromboprophylaxis protocol. To our knowledge, this is the first report describing the incidence and predictors of DVT in abdominal, GI, and HBP oncologic surgery. In this study, we used DUS to investigate patients for DVT because it is a safer and easier diagnostic procedure than venography [10]. The overall diagnostic accuracy of DUS is reported to be relatively high, with an estimated positive predictive value of 80% and negative predictive value of 82% [11]. As two licensed advanced vascular technologists performed all DUS procedures in this study, the procedures were considered to satisfy this level of accuracy. The present study revealed that female gender, high preoperative D-dimer level, and lower BMI were predictors of DVT after abdominal oncologic surgery. It is known that the incidence of DVT is higher in females in association with pregnancy, gynecological surgery, and contraceptive medications [12,13]. Our data indicate that female gender could be a risk factor for the development of DVT in the postmenopausal age group. D-dimer level is the most sensitive marker of intravascular coagulation, and there is a strong correlation between increased D-dimer level and DVT [14]. A high preoperative D-dimer level was an independent predictor of postoperative DVT in the present study, indicating that intravascular coagulation had already been activated before surgery in patients with cancer. Therefore, our data show that preoperative screening using D-dimer levels would be useful for identifying patients at high risk of perioperative DVT. Furthermore, preoperative DUS screening for the patients with high D-dimer levels would be useful to rule out preoperative DVT. As early postoperative D-dimer levels are affected by various factors other than thromboembolism, such as surgical damage to vessels and organs, the specificity of the test is too low to be of diagnostic value during this period. Lower BMI was also a predictor of postoperative DVT in this study. Although obesity is considered to be a risk factor for DVT, previous reports have shown that obesity is not a risk factor for perioperative DVT [15,16]. It is possible that direct continuous compression of the veins during perioperative immobility has a greater effect on patients with a lower BMI because we mostly detected early DVT after surgery. In Japan, we rarely encounter a clinically obese patient, and there was only one case whose BMI was >35 kg/m2 in this study. Therefore, the present study would not be able to conclude that obesity was not a risk factor of perioperative DVT. Laparoscopic procedures have gained wide acceptance and application in abdominal oncologic surgery. However, there is still controversy regarding whether laparoscopic surgery is a risk factor for perioperative DVT [12,17]. Reduced tissue damage and earlier mobilization may reduce the incidence of DVT after laparoscopic surgery. On the other hand, laparoscopic surgery causes increased venous stasis because of pneumoperitoneum, prolonged Trendelenburg position, and longer operation time. In the present study, the incidence of DVT was higher after laparoscopic surgery than after open surgery (40.0% versus 23.1%), but this difference was not statistically significant. The incidence of DVT was significantly
lower in patients who underwent HBP surgery compared with those who underwent GI surgery. In our series, the preoperative and postoperative prothrombin time and activated partial thromboplastin time were significantly disturbed in patients with HBP surgery compared with those with GI surgery (data not shown). The disturbance of coagulation function because of hepatic resection and/or hepatic dysfunction may reduce the risk of developing DVT after HBP surgery. Our data showed that pharmacologic prophylaxis is not needed after HBP oncologic surgery. In summary, our observational screening using DUS showed that the incidence of postoperative DVT was high in patients who underwent abdominal oncologic surgery. We propose that pharmacologic thromboprophylaxis is essential for patients with high risk factors.
Acknowledgment The authors thank the vascular technologists, Mr Shigeru Hashimoto, Ms Tomoe Kanai, and Mr Yoshitsugu Shirakawa. This study was supported in part by a grant-in-aid for scientific research from the Japan Society for the Promotion of Science, Tokyo, Japan. Conflict of interest statement: The authors have no conflicts of interest.
references
[1] Geerts WH, Pineo GF, Heit JA, et al. Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126: 338S. [2] 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;4:581. [3] Bottaro FJ, Elizondo MC, Doti C, et al. Efficacy of extended thrombo-prophylaxis in major abdominal surgery: what does the evidence show? A meta-analysis. Thromb Haemost 2008;99:1104. [4] Lyman GH, Khorana AA, Falanga A, et al. American Society of Clinical Oncology guideline: recommendations for venous thromboembolism prophylaxis and treatment in patients with cancer. J Clin Oncol 2007;25:5490. [5] Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133:381S. [6] Glotzbecker MP, Bono CM, Wood KB, Harris MB. Postoperative spinal epidural hematoma: a systematic review. Spine (Phila Pa 1976) 2010;35:E413. [7] Goodacre S, Sampson F, Thomas S, van Beek E, Sutton A. Systematic review and meta-analysis of the diagnostic accuracy of ultrasonography for deep vein thrombosis. BMC Med Imaging 2005;5:6. [8] Akl EA, Terrenato I, Barba M, Sperati F, Muti P, Schunemann HJ. Extended perioperative thromboprophylaxis in patients with cancer. A systematic review. Thromb Haemost 2008;100:1176. [9] Hutten BA, Prins MH, Gent M, Ginsberg J, Tijssen JG, Buller HR. Incidence of recurrent thromboembolic and bleeding complications among patients with venous thromboembolism
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[10] [11]
[12]
[13]
in relation to both malignancy and achieved international normalized ratio: a retrospective analysis. J Clin Oncol 2000; 18:3078. Pini M, Marchini L, Giordano A. Diagnostic strategies in venous thromboembolism. Haematologica 1999;84:535. Kearon C, Julian JA, Newman TE, Ginsberg JS. Noninvasive diagnosis of deep venous thrombosis. McMaster Diagnostic Imaging Practice Guidelines Initiative. Ann Intern Med 1998; 128:663. Nick AM, Schmeler KM, Frumovitz MM, et al. Risk of thromboembolic disease in patients undergoing laparoscopic gynecologic surgery. Obstet Gynecol 2010;116:956. Rosenberg VA, Lockwood CJ. Thromboembolism in pregnancy. Obstet Gynecol Clin North Am 2007;34:481.
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[14] Turkstra F, van Beek EJ, ten Cate JW, Buller HR. Reliable rapid blood test for the exclusion of venous thromboembolism in symptomatic outpatients. Thromb Haemost 1996;76:9. [15] Prystowsky JB, Morasch MD, Eskandari MK, Hungness ES, Nagle AP. Prospective analysis of the incidence of deep venous thrombosis in bariatric surgery patients. Surgery 2005;138:759. discussion 763e755. [16] Westling A, Bergqvist D, Bostrom A, Karacagil S, Gustavsson S. Incidence of deep venous thrombosis in patients undergoing obesity surgery. World J Surg 2002;26:470. [17] Buchberg B, Masoomi H, Lusby K, et al. Incidence and risk factors of venous thromboembolism in colorectal surgery: does laparoscopy impart an advantage? Arch Surg 2011; 146:739.
Available online at www.sciencedirect.com
journal homepage: www.JournalofSurgicalResearch.com
Incidence and predictors of deep venous thrombosis after abdominal oncologic surgery: Prospective Doppler ultrasound screening Keishi Sugimachi, MD, PhD,a,b,* Hirotada Tajiri, MD,a Nao Kinjo, MD, PhD,a Masahiko Ikebe, MD, PhD,a Huanlin Wang, MD,a Kiyoshi Tanaka, MD, PhD,c Junko Tanaka, MD, PhD,a Shuichi Tsukamoto, MD, PhD,a Shinsuke Mii, MD, PhD,c and Hidefumi Higashi, MD, PhDa a
Department of Surgery, Steel Memorial Yawata Hospital, Kitakyushu, Japan Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan c Department of Vascular Surgery, Steel Memorial Yawata Hospital, Kitakyushu, Japan b
article info
abstract
Article history:
Background: Venous thromboembolism is a relatively rare but serious complication of
Received 6 March 2012
abdominal surgery. This study evaluated the incidence and risk factors for the develop-
Received in revised form
ment of deep venous thrombosis (DVT) after abdominal oncologic surgery using color
21 May 2012
Doppler ultrasonography (DUS).
Accepted 1 June 2012
Methods: This study enrolled 132 consecutive patients who underwent elective abdominal
Available online 20 June 2012
surgery for malignant tumors. Patients were investigated for DVT using DUS on postoperative day 7 2. Correlations between the incidence of DVT and clinicopathologic
Keywords:
parameters and the postoperative course were evaluated.
Deep venous thrombosis
Results: DVT was found in 15 patients (11.4%) using DUS. Clinically evident venous
Abdominal surgery
thromboembolism, including pulmonary embolism, was not found in these patients. The
Doppler ultrasonography
incidence of DVT was significantly higher in females (P ¼ 0.002), patients with a lower body mass index (P ¼ 0.008), and patients with a higher preoperative D-dimer level (P < 0.0001). Conclusions: DUS is noninvasive and is useful for postoperative DVT screening. Thromboprophylaxis is essential in high-risk patients who have undergone abdominal oncologic surgery. ª 2012 Elsevier Inc. All rights reserved.
1.
Introduction
The overall incidence of venous thromboembolism (VTE) in patients who have undergone general surgery without prophylactic treatment is reported to be approximately 29% in
the Western countries [1] and 24% in Japan [2]. VTE, presenting as deep venous thrombosis (DVT) or pulmonary embolism, may be a serious life-threatening complication after major abdominal surgery [1]. Major abdominal surgery promotes a hypercoagulable state that increases the expected risk of
* Corresponding author. Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Tsurumi, Beppu 874-0838, Japan. Tel.: þ81 977 27 1650; fax: þ81 977 27 1651. E-mail address: [email protected] (K. Sugimachi). 0022-4804/$ e see front matter ª 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jss.2012.06.002
658
j o u r n a l o f s u r g i c a l r e s e a r c h 1 7 8 ( 2 0 1 2 ) 6 5 7 e6 6 1
VTE associated with immobilization [3]. Patients with active malignancy also have a higher risk of developing DVT in the perioperative period [4]. In the eighth edition of the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines, administration of postoperative lowemolecular-weight heparin, low-dose unfractionated heparin, or fondaparinux for VTE prophylaxis after high-risk major abdominal surgery has a grade 1A indication [5]. However, the increased risk of postoperative bleeding, especially the risk of epidural hematoma associated with epidural anesthesia, is a serious potential consequence of using pharmacologic prophylaxis for VTE [6]. To establish effective and safe strategies for prophylaxis, more accurate information on the incidence of DVT in patients who have undergone oncologic surgery is needed. To our knowledge, this is the first study assessing the incidence of DVT after abdominal oncologic surgery using Doppler ultrasonography (DUS). The objective of this study was to evaluate the incidence and predictors of DVT after abdominal oncologic surgery.
2.
Materials and methods
2.1.
Patients
From January to December 2011, 132 consecutive patients who underwent elective abdominal oncologic surgery at our institute were enrolled in the study preoperatively. There were no exclusion criteria, but the patients who could not be performed postoperative DUS were excluded. Data from all these patients were analyzed. This prospective observational study was approved by the Ethics and Indications Committee of Steel Memorial Yawata Hospital. Patient data are summarized in Table 1. The median age of the patients was 71 y (range, 42e94 y).
2.2.
Operative procedure and postoperative care
In the present study, there was no intention to select the method of DVT prophylaxis. The intermittent sequential pneumatic compression device (Kendall SCD Response Sequential Compression System; Covidien Japan, Tokyo, Japan) and compression stockings were used in 130 (98.5%) of 132 patients during the operation and until the patients were ambulatory postoperatively. Pharmacologic prophylaxis was administered to 16 (12.1%) of 132 patients. Fondaparinux (Xa inhibitor) was used in 15 patients, and enoxaparin was used in one patient. Pharmacologic prophylaxis was started after the epidural catheter was removed in all patients. Patients were encouraged to ambulate postoperatively by the advanced physical therapists.
2.3.
Table 1 e Characteristics of the 132 patients in this study. Characteristics Age (y) Sex Male Female BMI (kg/m2) Diabetes Hypertension VTE history Central venous catheter Preoperative chemotherapy Indication for surgery Esophageal cancer Gastric cancer Colorectal cancer Hepatic cancer Pancreaticobiliary cancer Operative position Supine Lithotomy Lateral Operation time (min) Blood loss (g) Laparoscopic surgery Anesthesia General General þ epidural Mechanical DVT prophylaxis Pharmacologic DVT prophylaxis
Mean SD (range)/n (%) 70.7 9.6 (42e94) 91 (69) 41 (31) 22.5 3.5 (14.5e8.1) 27 (20) 67 (51) 1 (1) 22 (17) 20 (15) 6 26 45 48 7 80 33 19 234 138 241 359 33 45 87 131 16
(5) (20) (34) (36) (5) (61) (25) (14) (35e690) (10e2050) (25) (34) (66) (99) (12)
SD ¼ standard deviation.
femoral veins were imaged. The patient was then placed in a sitting position, and the popliteal vein in the popliteal fossa, soleus, peroneal, and tibial veins were imaged. The veins were imaged in gray scale to detect thrombosis and respiratory movement, and compressibility was assessed in the sagittal and coronal planes. Vascular flow was assessed by color Doppler analysis. The images were recorded using a 7.5 MHz linear transducer (LOGIQ S8; GE Healthcare UK Ltd, Buckinghamshire, England). The results of DUS were classified as abnormal if thrombosis was detected or if the venous segments imaged were not compressible (Fig. 1) [7].
2.4.
Statistical analysis
All statistical analyses were performed using JMP 8.0 software (SAS Institute Inc, Cary, NC). All variables were expressed as the mean standard deviation. Continuous variables were compared using the ManneWhitney U test. Categorical data were compared using the c2 test. Logistic regression analysis was performed to identify the independent predictors of DVT. A P value of <0.05 was regarded as statistically significant.
Ultrasonographic diagnosis of DVT
Patients were investigated for DVT using DUS on postoperative day 7 2. DUS was performed by licensed clinical vascular technologists (Japanese Society of Vascular Surgery, Japanese College of Angiology, and Japanese Society of Phlebology). First, each patient was scanned in the supine position. The common femoral, superficial femoral, and deep
3.
Results
3.1.
Incidence of DVT
DVT was detected in 15 patients (11.4%) by DUS. No patients showed any clinical symptoms related to DVT. The location of
659
j o u r n a l o f s u r g i c a l r e s e a r c h 1 7 8 ( 2 0 1 2 ) 6 5 7 e6 6 1
Table 2 e Relationships between clinicopathologic parameters and DVT after abdominal oncologic surgery.
Fig. 1 e Ultrasonographic images of DVT in the soleus vein. (A) Sagittal view and (B) coronal view. (Color version of figure is available online.)
DVT was the left soleus vein in nine cases (60%), bilateral soleus veins in two cases (13%), left peroneal vein in two cases (13%), left femoral vein in one case (7%), and bilateral external iliac veins in one case (7%). Therefore, DVT occurred in the left limb in 12 cases (80%) and in a distal vein in 13 cases (87%). All the 15 patients had received mechanical prophylaxis since the start of their operation, and pharmacologic prophylaxis had been initiated before DVT was diagnosed in two cases. After DVT was diagnosed, these patients underwent anticoagulant therapy for up to 6 mo. There were no cases of pulmonary embolism during the follow-up period.
3.2.
Risk factors for DVT
Table 2 shows the clinicopathologic parameters related to the incidence of DVT after abdominal oncologic surgery. Ten (24%) of 41 female patients developed DVT, which was significantly higher than the proportion of male patients (5.5%) who developed DVT. The average body mass index (BMI) of patients with DVT was significantly lower than that of patients without DVT. Patients who underwent gastrointestinal (GI) surgery had a significantly higher incidence of DVT than those who underwent hepatobiliaryepancreatic (HBP) surgery. Preoperative D-dimer levels in patients with DVT were significantly higher than those in patients without DVT.
Parameters
VTE () (n ¼ 117)
VTE (þ) (n ¼ 15)
P value
Age (y) Sex Male Female BMI (kg/m2) Diabetes (%) Hypertension (%) Central venous catheter (%) Preoperative chemotherapy (%) Preoperative DD (mg/mL) Type of surgery GI HBP Operative position Supine Lithotomy Lateral Operation time (min) Blood loss (g) Blood transfusion Laparoscopic surgery Epidural anesthesia Pharmacologic prophylaxis Postoperative DD (POD 1) (mg/mL) Postoperative DD (POD 7) (mg/mL) Ambulation (d) Complication (þ)
70.2 0.9
73.9 2.5
0.913
86 31 22.8 0.3 25 (21.4) 59 (50.4) 20 (17.1) 17 (14.5)
5 10 20.5 0.9 2 (13.3) 8 (53.3) 2 (13.3) 3 (20.0)
0.002
1.7 0.4
7.1 1.1
65 (49.2) 52 (39.4)
13 (9.9) 2 (1.5)
72 (54.5) 27 (20.5) 18 (13.6) 234 13 259 33 24 (20.5) 27 (23.1) 77 (65.8) 14 (12.0) 7.1 0.6
8 (6.1) 6 (4.5) 1 (0.8) 229 36 101 92 3 (20.0) 6 (40.0) 10 (66.7) 2 (13.3) 10.6 1.9
0.891 0.109 0.963 0.173 0.948 0.880 0.076
10.8 0.9
14.3 2.6
0.219
1.9 0.3 23 (19.7)
1.9 0.7 6 (40.0)
0.996 0.092
0.016 0.448 0.832 0.701 0.591 <0.0001 0.014
0.312
DD ¼ D-dimer; POD ¼ postoperative day; GI ¼ gastrointestinal; HBP ¼ hepatobiliary-pancreatic. Data are presented as mean standard deviation or as n (%).
Postoperative D-dimer levels in patients with DVT tended to be higher than those in patients without DVT, but this difference was not statistically significant (P ¼ 0.07). Multivariate analysis showed that female gender, BMI <22 kg/m2, and preoperative D-dimer >3 mg/mL were independent predictors for the development of DVT after surgery (Table 3).
4.
Discussion
This study investigated the incidence of DVT in patients who had undergone abdominal oncologic surgery. Patients with cancer are reported to have a higher risk of VTE than those without cancer [8]. Moreover, thromboprophylaxis might be
Table 3 e Multivariate analysis predicting the incidence of DVT after abdominal oncologic surgery. Factors Sex: female Preoperative DD: >3 mg/mL BMI: <22 kg/m2
Odds ratio
95% CI
P value
2.83 2.80 3.62
1.34e6.74 1.17e7.25 1.37e16.8
0.009 0.023 0.029
CI ¼ confidence interval; DD ¼ D-dimer.
660
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less effective, and the risk of major bleeding might be higher, in patients with cancer than those without cancer [9]. It is therefore necessary to assess the risk factors for DVT in patients with cancer to establish an effective and safe thromboprophylaxis protocol. To our knowledge, this is the first report describing the incidence and predictors of DVT in abdominal, GI, and HBP oncologic surgery. In this study, we used DUS to investigate patients for DVT because it is a safer and easier diagnostic procedure than venography [10]. The overall diagnostic accuracy of DUS is reported to be relatively high, with an estimated positive predictive value of 80% and negative predictive value of 82% [11]. As two licensed advanced vascular technologists performed all DUS procedures in this study, the procedures were considered to satisfy this level of accuracy. The present study revealed that female gender, high preoperative D-dimer level, and lower BMI were predictors of DVT after abdominal oncologic surgery. It is known that the incidence of DVT is higher in females in association with pregnancy, gynecological surgery, and contraceptive medications [12,13]. Our data indicate that female gender could be a risk factor for the development of DVT in the postmenopausal age group. D-dimer level is the most sensitive marker of intravascular coagulation, and there is a strong correlation between increased D-dimer level and DVT [14]. A high preoperative D-dimer level was an independent predictor of postoperative DVT in the present study, indicating that intravascular coagulation had already been activated before surgery in patients with cancer. Therefore, our data show that preoperative screening using D-dimer levels would be useful for identifying patients at high risk of perioperative DVT. Furthermore, preoperative DUS screening for the patients with high D-dimer levels would be useful to rule out preoperative DVT. As early postoperative D-dimer levels are affected by various factors other than thromboembolism, such as surgical damage to vessels and organs, the specificity of the test is too low to be of diagnostic value during this period. Lower BMI was also a predictor of postoperative DVT in this study. Although obesity is considered to be a risk factor for DVT, previous reports have shown that obesity is not a risk factor for perioperative DVT [15,16]. It is possible that direct continuous compression of the veins during perioperative immobility has a greater effect on patients with a lower BMI because we mostly detected early DVT after surgery. In Japan, we rarely encounter a clinically obese patient, and there was only one case whose BMI was >35 kg/m2 in this study. Therefore, the present study would not be able to conclude that obesity was not a risk factor of perioperative DVT. Laparoscopic procedures have gained wide acceptance and application in abdominal oncologic surgery. However, there is still controversy regarding whether laparoscopic surgery is a risk factor for perioperative DVT [12,17]. Reduced tissue damage and earlier mobilization may reduce the incidence of DVT after laparoscopic surgery. On the other hand, laparoscopic surgery causes increased venous stasis because of pneumoperitoneum, prolonged Trendelenburg position, and longer operation time. In the present study, the incidence of DVT was higher after laparoscopic surgery than after open surgery (40.0% versus 23.1%), but this difference was not statistically significant. The incidence of DVT was significantly
lower in patients who underwent HBP surgery compared with those who underwent GI surgery. In our series, the preoperative and postoperative prothrombin time and activated partial thromboplastin time were significantly disturbed in patients with HBP surgery compared with those with GI surgery (data not shown). The disturbance of coagulation function because of hepatic resection and/or hepatic dysfunction may reduce the risk of developing DVT after HBP surgery. Our data showed that pharmacologic prophylaxis is not needed after HBP oncologic surgery. In summary, our observational screening using DUS showed that the incidence of postoperative DVT was high in patients who underwent abdominal oncologic surgery. We propose that pharmacologic thromboprophylaxis is essential for patients with high risk factors.
Acknowledgment The authors thank the vascular technologists, Mr Shigeru Hashimoto, Ms Tomoe Kanai, and Mr Yoshitsugu Shirakawa. This study was supported in part by a grant-in-aid for scientific research from the Japan Society for the Promotion of Science, Tokyo, Japan. Conflict of interest statement: The authors have no conflicts of interest.
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