Thromboembolism prevention in surgery of digestive cancer

Abstracts

RACIONAL: Tromboembolismo venoso é complicação frequente após tratamento cirúrgico em geral e, de um modo especial, na condução terapêutica do câncer. A cirurgia do aparelho digestivo tem sido referida como potencialmente indutora desta complicação. Os pacientes com câncer digestivo, têm risco substancialmente aumentado de iniciarem ou de terem recorrência de processo tromboembólico. OBJETIVO: Oferecer aos cirurgiões que atuam na cirurgia digestiva e geral orientação segura sobre como efetuar a tromboprofilaxia dos pacientes que necessitam de operações no tratamento de doenças malignas digestivas. MÉTODOS: A Diretriz foi baseada a partir da elaboração de 15 questões clínicas relevantes e relacionadas ao risco, tratamento e prognóstico do paciente submetido ao tratamento cirúrgico do câncer do aparelho digestivo. Elas focaram tanto os eventos tromboembólicos associados às operações quanto os aspectos relacionados à sua profilaxia. As questões foram estruturadas por meio do P.I.C.O. (Paciente, Intervenção ou Indicador, Comparação e Outcome), permitindo gerar estratégias de busca da evidência nas principais bases primárias de informação científica (Medline/Pubmed, Embase, Lilacs/Scielo, Cochrane Library, Premedline via OVID). Também foi realizada busca manual da evidência e de teses (BDTD e IBICT). A evidência recuperada foi selecionada a partir da avaliação crítica utilizando instrumentos (escores) discriminatórios de acordo com a categoria da questão: risco, terapêutica e prognóstico (JADAD para Ensaios Clínicos Randomizados e New Castle Otawa Scale para estudos não randômicos). Após definir os estudos potenciais para sustento das recomendações, eles foram selecionados pela força da evidência e grau de recomendação segundo a classificação de Oxford, incluindo a evidência disponível de maior força. RESULTADOS: Foram avaliados 53.555 trabalhos pelo título e/ou resumo. Deste total foram selecionados (1ª seleção) 478 trabalhos avaliados pelo texto completo. A partir deles, para sustentar as recomendações, foram incluídos neste consenso 132 trabalhos. As 15 perguntas formuladas puderam ser respondidas com artigos com grau de evidência correspondentes à 31 A, 130 B, 1 C e 0 D. CONCLUSÃO: Esta revisão possibilitou elaborar orientação segura para a profilaxia do tromboembolismo nas operações sobre o câncer do aparelho digestivo, abordando os tópicos mais frequentes do quotidiano do trabalho dos cirurgiões gerais e do aparelho digestivo.

Neoplasias; Trombose venosa; Heparina; Cirurgia

ORIGINAL ARTICLE

Thromboembolism prevention in surgery of digestive cancer

Osvaldo Malafaia; Andre Luís Montagnini; Angélica Luchese; Antonio Carlos Accetta; Bruno Zilberstein; Carlos Alberto Malheiros; Carlos Eduardo Jacob; Claudemiro Quireze-Junior; Cláudio José Caldas Bresciani; Cleber Dario Pinto Kruel; Ivan Cecconello; Eduardo Fonseca Sad; Jorge Alberto Langbeck Ohana; José Eduardo de Aguilar-Nascimento; José Eduardo Ferreira Manso; Jurandir Marcondes Ribas-Filho; Marco Aurélio Santo; Nelson Adami Andreollo; Orlando Jorge Martins Torres; Paulo Herman; Ronaldo Mafia Cuenca; Rubens Antônio Aissar Sallum; Wanderley Marques Bernardo

Brazilian College of Digestive Surgery - CBCD, São Paulo, SP, Brazil

Correspondence

ABSTRACT

BACKGROUND: The venous thromboembolism is a common complication after surgical treatment in general and, in particular, on the therapeutic management on cancer. Surgery of the digestive tract has been reported to induce this complication. Patients with digestive cancer have substantial increased risk of initial or recurrent thromboembolism.

AIM: To provide to surgeons working in digestive surgery and general surgery guidance on how to make safe thromboprophylaxis for patients requiring operations in the treatment of their gastrointestinal malignancies.

METHODS: The guideline was based on 15 relevant clinical issues and related to the risk factors, treatment and prognosis of the patient undergoing surgical treatment of cancer on digestive tract. They focused thromboembolic events associated with operations and thromboprophylaxis. The questions were structured using the PICO (Patient, Intervention or Indicator, Comparison and Outcome), allowing strategies to generate evidence on the main primary bases of scientific information (Medline / Pubmed, Embase, Lilacs / Scielo, Cochrane Library, PreMedline via OVID). Evidence manual search was also conducted (BDTD and IBICT). The evidence was recovered from the selected critical evaluation using discriminatory instruments (scores) according to the category of the question: risk, prognosis and therapy (JADAD Randomized Clinical Trials and New Castle Ottawa Scale for studies not randomized). After defining potential studies to support the recommendations, they were selected by the strength of evidence and grade of recommendation according to the classification of Oxford, including the available evidence of greater strength.

RESULTS: A total of 53,555 papers by title and / or abstract related to issue were found. Of this total were selected (1st selection) 478 studies that were evaluated as full-text. From them to support the recommendations were included in the consensus 132 papers. The 15 questions could be answered with evidence grade of articles with 31 A, 130 B, 1 C and 0 D.

CONCLUSION: It was possible to prepare safe recommendations as guidance for thromboembolism prophylaxis in operations on the digestive tract malignancies, addressing the most frequent topics of everyday work of digestive and general surgeons.

Headings: Neoplams. Venous thrombosis. Heparin. Surgery.

INTRODUCTION

Venous thromboembolism is a common complication after surgical treatment in general and, in particular, on management of cancer. Surgery of the digestive tract has been reported to potentially induce this complication. It has greater representation in certain anatomical segments and in the conditions that are associated patients risk factors.

The prevention of thromboembolism (VTE) is a subject of great importance in the daily practice of surgeons. There are several physical forms and drugs that can be used. In recent years new approaches, both with respect to physical maneuvers as in drug dosage have been studied with good methodology. These new approaches are still little known and also are by most surgeons. In cancer the importance of this topic is even greater than in benign diseases.

The Evidence-Based Medicine incorporates data of the most recent systematic reviews available in the literature causing various forms of scientific contributions. The most common are the Guidelines and the consensus.

The first, in Brazil, is made by the associations of specialties affiliated on the Brazilian Medical Association - AMB and the Federal Council of Medicine - CFM, and disclosed by these official entities of the medical profession. They are guides of good care practices answering questions that doctors have in their daily work. They do not replace the experience and expertise of medical care acquired as valid in their medical life. Furthermore, the Guidelines may not be complete or updated recently, since much new publications may not have been incorporated in the latest issue. Users should be encouraged to seek update from the date of publication of the guide till present, the studies that could impact the diagnosis and treatment of their patients in the period of time that separates the official release and the date of service.

The second, is to suggest recommendations to the points where the evidence is not of high degree or do not exist. The best, by its high degree of evidence, are unquestionable and are usually only homologated by the consensus group. The meeting of experienced and renowned experts in the field to discuss the controversial points is crucial in guiding medical attitudes on topics difficult to approach. Normally these consensuses substantiate the subsequent creation of the Guidelines issued by the official classes. To have to better validity, the papers in witch the consensuses are based on must be printed in journals with good indexation and blindly peer-reviewed. The major indicators of the quality of these journals are the impact factor and international access.

Circumstantial and genetic factors increase the risk of VTE. The recognition of these factors is essential to be able to deal with higher accuracy and efficiency. Several risk classifications have been proposed over time and some based on researches carried out with a high degree of evidence. However, updated guidance is always needed. It should add to the existing evidence the medical possibilities of its application and also the patients conditions. The Brazilian College of Digestive Surgery is collaborating with AMB and CFM in formulating the Guidelines, in which this consensus can be transformed. The theme disclosed herein was motivated by the importance it has in prevention of thromboembolism in pre and post-operative abdominal operations for cancer. In recent years, due to new and interesting features that were added to this theme, medical attitudes are forced in a rethink.

Therefore, the aim of this consensus is to recommend to surgeons who work in cancer of the digestive system (CAD) the latest possibilities in the management and prevention of VTE, based on Evidence-Based Medicine.

METHODS

Description of the method of collecting evidence

The Guideline / consensus was based on 15 relevant clinical issues and their related risk on treatment and prognosis of the patient undergoing surgical treatment for cancer of the digestive system (the statements are described in the results). They focused thromboembolic events associated with operations and thromboprophylaxis. The questions were structured using the PICO (Patient, Intervention or Indicator, Comparison and Outcome), allowing strategies to generate evidence on the main primary bases of scientific information (Medline / Pubmed, Embase, Lilacs / Scielo, Cochrane Library, Premedline via OVID). Manual search was also conducted looking for evidences on academic theses (BDTD and IBICT).

The evidence was recovered from the selected critical assessment using discriminatory instruments (scores) according to the category of the question: risk, prognosis and therapy (JADAD Randomized Clinical Trials and New Castle Ottawa Scale for not random studies). After defining potential studies to support the recommendations, they were selected by the strength of evidence and grade of recommendation according to the classification of Oxford (available at www.cebm.net), including evidence of greater strength (available at www.cbcd.org.br).

Summary of grades of evidence and strength of recommendation

Were classified into the following grades: A - experimental or observational studies with better consistency; B - experimental or observational studies with less consistent; C - case reports (uncontrolled studies); D - opinion without critical evaluation, based on consensus, physiological or animal models studies.

The inclusion criteria used to support the recommendations, regarding PICO, varied with the question, but generally were based on patients with digestive cancer who underwent to curative or palliative operations; and / or evidence extrapolated from populations with cancer; and / or patients undergoing abdominal surgical interventions; pharmacological or non-pharmacological thromboprophylaxis; in the primary prevention of venous thromboembolic events; outcomes related to deep vein thrombosis, pulmonary embolism, bleeding events, mortality and complications in the perioperative period.

Were evaluated 53,555 papers by title and / or abstract. Of this total were selected (1st selection) 478 studies evaluated the full text. From them to support the recommendations were included in the consensus 132 papers. The individual numerical synthesis used is described in parentheses after each recommendation. The full text is available at www.cbcd.org.br

RESULTS

The 15 questions could be answered with articles of levels of evidence corresponding to 31 A, 130 B, 1 C and none D in total. The final recommendations from consensus to each question are described below. In each is mentioned the numerical synthesis of the reviewed papers, and in parentheses are: 1) the total reviewed; 2) the total after first selection; 3) the number of articles included that supported the recommendations.

The abstracts of the articles and their original forms (full text) used as references for recommendations are available on the website of CBCD: www.cbcd.org.br sector highlighted as "Prevention of thromboembolism in surgery of cancer of the digestive system" (the authors encourage readers to access these supplements in reading this article).

The final recommendations were:

Question 1. The surgical patient with CAD has pre and post-operative increased the risk of VTE?

Recommendation: There is an increased risk of VTE in patients with malignancy of the digestive system in pre and postoperative period, including after discharge. Risk factors (tumor site, stage, chemotherapy, age, etc.) should be considered in decision of making thromboprophylaxis ^{10,19,40,53,67,69,71,75,83,89,107,108,111,118,125,132. (Recovered = 6241; first selection = 61, included = 16).}

Question 2. There are differences between the locations of CAD and the risk of postoperative VTE (esophagus, stomach, liver, pancreas, colon, rectum)?

Recommendation: After operation for gastrointestinal cancer, the data show that VTE is associated with tumor location, inducing specific postoperative care ^{10,19,40,53,67,69,71,75,83,89,107,108,111,118,125,132. (Recovered = 6241, first selection = 61; included = 16).}

Question 3. The approach by laparotomy or laparoscopy in CAD modifies the risk of VTE?

Recommendation: The laparoscopic operation, as an independent variable, does not modify the risk of thromboembolism (venous and / or pulmonary) in patients with CAD, and the indication for perioperative thromboprophylaxis is similar to open operations ^{17.18, 28,41,61,63,70,73,77,78,80,81,115,121,124. (Recovered = 23012; first selection = 55; included = 15)}

Question 4. Should be employed instruments of risk stratification of VTE in the preoperative evaluation of patients with CAD? Which are the most common ? Which are validated?

Recommendation: The instruments for predicting risk of thromboembolic events in hospitalized patients (clinical or surgical) and / or with cancer (curative or palliative) are influenced by many factors (biases). There are no tools to estimate accurately the risk of VTE in these patients. However, there are independent risk factors (clinical and laboratory) that, when present, justify thromboprophylaxis in any of the levels of risk (low, intermediate or high)^{1,6,7,9,19,23,30,53,54 , 55,59,87,96,99,104,109,110,120,125,131. (Recovered = 9982; first selection = 117; included = 20)}

Question 5. The pharmacologic prophylaxis with heparin, low molecular weight heparin (LMWH) may decrease the risk of VTE in the postoperative patient with CAD?

Recommendation: Prophylaxis with low molecular weight heparin reduces the risk of thromboembolic events in patients with abdominal operation for cancer, compared to those who did not receive thromboprophylaxis. There is no statistically significant difference between the various types of low molecular weight heparins for efficacy ^{1,16,22,29,42,43,50,53,67,72,86,94,98,100,105,122. (Recovered = 5806; first selection = 142; included = 16)}

Question 6. The pharmacological prophylaxis with unfractionated heparin can decrease the risk of VTE in the postoperative patient with CAD?

Recommendation: Use of unfractionated heparin before abdominal operations (with and without cancer) in a dose of 5000 IU SC and, then, every eight hours for five to eight days, reduces the risk of post-operative thromboembolic events without increasing significantly the risk of bleeding events ^{16,25,27,35,44,50,57,62,90,95,103,114. (Recovered = 5806; first selection = 142; included = 12)}

Question 7. Is there a difference in efficacy between LMWH and unfractionated heparin in the prophylaxis of VTE in patients with CAD?

Recommendation: There is no difference in the occurrence of thromboembolic events (deep venous thrombosis or pulmonary embolism) with the use of low molecular weight heparin or unfractionated heparin in most of the evidence extrapolated to patients undergoing abdominal or general surgery for cancer (35% to 63% of cases). However, in a small part of evidence also extrapolated, when exists difference between the two forms of thromboprophylaxis, it favors the use of low molecular weight heparin, with reduction in bleeding events, in wall hematoma and reoperation for bleeding ^{3,13,15,26,31,34,35,38,45,48,64,74,76,84,101. (Recovered = 5806; first selection = 142; included = 15)}

Question 8. Physical methods are effective in the prophylaxis of VTE? Can replace heparin in the prophylaxis of VTE in patients with CAD?

Recommendation: Physical methods, when properly used, are effective in reducing the risk of thromboembolic event(s). However, they should not replace the pharmacological prophylaxis, and this pharmacological treatment should it be reassume as soon as contraindications cease. The combined use of physical methods, especially graduated compression stockings with low-dose heparin thromboprophylaxis in the perioperative, increases the benefit in reducing the risk of thromboembolic events ^{4,21,51,82,88,92,114,117,126,128,129,130. (Recovered = 3377, first selection = 52; included = 12)}

Question 9. What is the recommended dosage regimen of heparin in the prophylaxis of VTE in surgical patients with CAD?

Recommendation: In the evaluation of prophylaxis for venous thromboembolism in patients undergoing abdominal surgery for cancer, there is no difference between the various treatment regimens with various types of heparin on the occurrence of thromboembolic outcomes. Nonetheless, the available evidence supports the recommendation of 5000 IU every eight hours for unfractionated heparin; for low molecular weight heparins - enoxaparin, dalteparin and nadroparin - the doses are recommended by manufacturers ^{12,22,29 , 31,34,50,74,86,95,100,105. (Recovered = 5806; first selection = 142; included = 11)}

Question 10. At what moment should be initiated pharmacological VTE prophylaxis?

Recommendation: The beginning of the use of unfractionated heparin before surgery reduces the risk of thromboembolic event compared to its exclusive use in the postoperative period. The low molecular weight heparin preoperatively may be recommended by extrapolating the comparison with unfractionated heparin preoperatively. The unfractionated heparin can be initiated in one to two hours before surgery. The use of heparin of low molecular weight should preferably be done 12 hours before the procedure; however, two hours before the start appears to be safe since it does not interfere with the anesthesia ^{3,12,29,31,33,42,43, 72,74,95,97,98. (Recovered = 5806; first selection = 142; included = 12)}

Question 11. The resumption of deambulation in the postoperative period allows the suspension of pharmacological prophylaxis of VTE or obtaining better results in prophylaxis?

Recommendation: Deambulation (day 1 postoperatively) should be encouraged, but there is no way to estimate the magnitude of their benefit in thromboprophylaxis and, so, is not allowed to replace the latter, even in patients at low risk of thrombosis ^{24 , 66,85,94,112,116,119,123. (Recovered = 3576; first selection = 26; included = 8).}

Question 12. How long must be maintained at pharmacological prophylaxis of VTE in the postoperative patient with CAD? There is benefit in extended prophylaxis (up to four weeks)?

Recommendation: The pharmacological thromboprophylaxis in postoperative patients with operations for cancer of the digestive system - extrapolating to other abdominal cancers - should be maintained for seven to ten days after surgery. Although still under investigation, the current trend suggests the extent of thromboprophylaxis for up to four weeks after surgery ^{5,11,34,42,46,47,60,72,93,98,99,105,112,132. (Recovered = 5806; first selection = 142, included = 14)}

Question 13. There is a need to adjust the doses of heparin in the prophylaxis of VTE of obese patients with CAD? If yes, from which BMI?

Recommendation: Although the existence of available evidences that the stratification of the heparin dose based on BMI can be safe and effective on thromboprophylaxis in obese patients undergoing bariatric surgery, this evidence should not be extrapolated to patients undergoing cancer operations on digestive tract; in this situation the stratification has not been adequately studied ^{20,32,39,52,59,65,68,91,102,106,127. (Recovered = 1561; first selection = 25; included = 11)}

Question 14. The pharmacological prophylaxis increases the risk of bleeding during and after surgery in patients with CAD operations?

Recommendation: There is also no difference in the occurrence of bleeding and increased risk of intraoperative or postoperative bleeding regarding the use of low molecular weight heparin or unfractionated heparin in most evidence extrapolated to patients undergoing general surgery or by abdominal malignancy. Nevertheless, the use of thromboprophylaxis compared with not using heparin perioperatively, may increase postoperative bleeding events ^{3,13,35,42,43,47,64,72,74,94,95,98,103,105,122. (Recovered = 5806; first selection = 142; included = 15)}

Question 15. There are medical conditions that contraindicate the use of heparin in the prophylaxis of VTE in CAD operations?

Recommendation: The contraindications for thromboprophylaxis in patients that carry digestive tract surgery - extrapolating to elderly with cancer without surgery - may be particularly hypersensitivity to heparin, septic endocarditis, hemorrhagic stroke, documented bleeding diathesis, treatment with anticoagulant or platelet antiaggregant, and renal or hepatic dysfunction^{12,14,15,16,22,31,37,38,42,72,86,95,103. (Recovered = 5806; first selection = 142; included = 13)}

DISCUSSION

Evidence-based research is an arduous task and requires experience. Initially are raised all correlated existent papers in major virtual libraries, crossing appropriated headings. This search generates a very large amount of articles, like what happened here. There were 53,555 papers by title and / or abstract, number impossible to be handled. Through filters, the search technique greatly reduces the amount, looking for uniformity of topics. Then, by reading the full text is obtained the homogeneity among the items. This reduces the total to a much smaller number to be used on the recommendations. Even this way, the final number of articles is large, as in this case: 132.

As expect, the theme of thromboprophylaxis is very broad and difficult to search. This fact can be recognized by the dispersion of selected articles in their degrees of evidence: 31 A, 130 B, 1 C and 0 D. However, the number with the highest grades (A + B) was good (131) and ensures reliability of these recommendations.

The Guideline is characterized by answering practical questions of the day-to-day medical practice. This one now presented, do not intent to be exhaustive. It was focused on the most frequent questions from the daily practice of the digestive surgeon forward to the prevention of thromboembolism, and tried to be objective, quick and easy understanding. Were removed from the text all the details of the exhaustive search (only because there is no editorial space to insert them) and they were placed on the CBCD web site where all studies can be checked and read in its entirety. The authors think that this interactivity easily accessible, can collaborate with continued education in digestive surgery. On CBCD site there is special attention to this consensus, freely available. Like any guideline, it is not intended that the reader faces these recommendations in a dogmatic way, but as a guidance. The clinical expertise is irreplaceable in moments of decision and these recommendations wish to be a safe tool for surgeons to help their decisions.

As can be seen by the low amount of references with higher degrees in relationship to total, is important the community to expand the academic research on thromboembolism. Only in this way and through prospective studies with better methodology, will be possible to increase the security of guidelines for the practice of thromboprophylaxis.

The CBCD will make efforts to transform this consensus in AMB / CFM Guideline, giving even more strength and respectability to it. But even so, due to the constant and uninterrupted publishing articles with new methods of treatment, this theme will continue to be updated by CBCD. The dynamism of research in the area is very large - although with only moderate evidence - requiring constant updating. The intention is that, by reading this article, our surgeons are guaranteed that they are offering the best for their patients by the time of the publication.

Recent estimations, shows that Brazil is aging. Thus, special attention should be given to the research of thromboembolism in the elderly. The recommendations will change? Only time and authors commitment in the theme will provide the answer.

Finally, the main objective of this exhausting paper was focused on the reduction of the morbidity and mortality of surgical procedures on the digestive tract. Proper management on prevention of thromboembolism results in lower costs in the overall patients care, reduces hospital stay and improves quality of life to those who come to us looking for high level of medical assistance.

CONCLUSIONS

This consensus could develop safe guidance for the prophylaxis of thromboembolism in operations of the digestive system cancer, answering the most frequent questions of everyday practice in general and digestive tract surgery.

Affiliations of the members of the consensus group:

Osvaldo Malafaia, Universidade Federal do Paraná, Curitiba, PR; Andre Luís Montagnini, Universidade de São Paulo, São Paulo, SP; Angélica Luchese, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS; Antonio Carlos Accetta, Instituto Nacional do Câncer, Rio de Janeiro, RJ; Bruno Zilberstein, Universidade de São Paulo, São Paulo, SP; Carlos Alberto Malheiros, Faculdade de Ciências Médicas da Santa Casa de Misericórdia de São Paulo, São Paulo, SP; Carlos Eduardo Jacob, Universidade de São Paulo, São Paulo, SP; Claudemiro Quireze Junior, Universidade Federal do Goiás, Goiânia, GO; Cláudio José Caldas Bresciani, Universidade de São Paulo, São Paulo, SP; Cleber Dario Pinto Kruel, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS; Ivan Cecconello, Universidade de São Paulo, São Paulo, SP; Eduardo Fonseca SAD, Hospital Luxemburgo, Belo Horizonte, MG; Jorge Alberto Langbeck Ohana, Universidade Federal do Pará, Belém, PA; José Eduardo de Aguilar-Nascimento, Universidade Federal do Mato Grosso, Cuiabá, MT; José Eduardo Ferreira Manso, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ; Jurandir Marcondes Ribas Filho, Faculdade Evangélica do Paraná, Curitiba, PR; Marco Aurélio Santo, Universidade de São Paulo, São Paulo, SP; Nelson Adami Andreollo, Universidade Estadual de Campinas, Campinas, SP; Orlando Jorge Martins Torres, Universidade Federal do Maranhão, São Luis, MA; Paulo Herman, Universidade de São Paulo, São Paulo, SP; Ronaldo Mafia Cuenca, Universidade de Brasília, DF; Rubens Antônio Aissar Sallum, Universidade de São Paulo, São Paulo, SP; Wanderley Marques Bernardo, Universidade de São Paulo, São Paulo, SP.

REFERENCES

• 1. Agnelli G, Bergqvist D, Cohen AT, Gallus AS, Gent M; PEGASUS investigators. Randomized clinical trial of postoperative fondaparinux versus perioperative dalteparin for prevention of venous thromboembolism in high-risk abdominal surgery. Br J Surg 2005;92:1212-20. PMID: 16175516.
• 2. Agnelli G, Bolis G, Capussotti L, Scarpa RM, Tonelli F, Bonizzoni E, et al. A clinical outcome-based prospective study on venous thromboembolism after cancer surgery: the @RISTOSproject. Ann Surg 2006;243:89-95. PMID: 16371741
• 3. Akl EA, Labedi N, Terrenato I, Barba M, Sperati F, Sempos EV, et al. Low molecular weight heparin versus unfractionated heparin for perioperative thromboprophylaxis in patients with cancer. Cochrane Database Syst Rev 2011;(11):CD009447. PMID: 22071865.
• 4. Allan A, Williams JT, Bolton JP, Le Quesne LP. The use of graduated compression stockings in the prevention of postoperative deep vein thrombosis. Br J Surg 1983;70:172-4. PMID: 6338992.
• 5. Auer R, Scheer A, Wells PS, Boushey R, Asmis T, Jonker D, et al. The use of extended perioperative low molecular weight heparin (tinzaparin) to improve disease-free survival following surgical resection of colon cancer: a pilot randomized controlled trial. Blood Coagul Fibrinolysis 2011;22:760-2. PMID: 22198365.
• 6. Ay C, Dunkler D, Marosi C, Chiriac AL, Vormittag R, Simanek R, et al. Prediction of venous thromboembolism in cancer patients. Blood 2010;116:5377-82. PMID: 20829374.
• 7. Ay C, Dunkler D, Simanek R, Thaler J, Koder S, Marosi C, et al. Prediction of venous thromboembolism in patients with cancer by measuring thrombin generation: results from the Vienna Cancer and Thrombosis Study. J Clin Oncol 2011;29:2099-103. PMID: 21464402.
• 8. Ay C, Vormittag R, Dunkler D, Simanek R, Chiriac AL, Drach J, et al. D-dimer and prothrombin fragment 1 + 2 predict venous thromboembolism in patients with cancer: results from the Vienna Cancer and Thrombosis Study. J Clin Oncol 2009;27:4124-9. PMID: 19636003.
• 9. Barbar S, Noventa F, Rossetto V, Ferrari A, Brandolin B, Perlati M, et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost 2010;8:2450-7. PMID: 20738765.
• 10. Berger AC, Scott WJ, Freedman G, Konski A, Weiner L, Cheng JD, Goldberg M. Morbidity and mortality are not increased after induction chemoradiotherapy followed by esophagectomy in patients with esophageal cancer. Semin Oncol. 2005 Dec;32(6 Suppl 9):S16-20. PubMed PMID: 16399424.
• 11. Bergqvist D, Agnelli G, Cohen AT, Eldor A, Nilsson PE, Le Moigne-Amrani A, et al. Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer. N Engl J Med 2002;346:975-80. PMID: 11919306.
• 12. Bergqvist D, Burmark US, Flordal PA, Frisell J, Hallböök T, Hedberg M, et al. Low molecular weight heparin started before surgery as prophylaxis against deep vein thrombosis: 2500 versus 5000 XaI units in 2070 patients. Br J Surg 1995;82:496-501. PMID: 7613894.
• 13. Bergqvist D, Burmark US, Frisell J, Guilbaud O, Hallböök T, Horn A, Lindhagen A, Ljungner H, Ljungström KG, general abdominal surgery: a comparison with low-dose heparin. Semin Thromb Hemost 1990;16 Suppl:19-24. PMID: 1962900.
• 14. Bergqvist D, Burmark US, Frisell J, Guilbaud O, Hallböök T, Horn A, et al. Thromboprophylactic effect of low molecular weight heparin started in the evening before elective general abdominal surgery: a comparison with low-dose heparin. Semin Thromb Hemost 1990;16 Suppl:19-24. PMID: 1962900.
• 15. Bergqvist D, Lindgren B, Mätzsch T. Comparison of the cost of preventing postoperative deep vein thrombosis with either unfractionated or low molecular weight heparin. Br J Surg 1996;83:1548-52. PMID: 9014669.
• 16. Bergqvist D, Mätzsch T, Burmark US, Frisell J, Guilbaud O, Hallböök T, et al. Low molecular weight heparin given the evening before surgery compared with conventional low-dose heparin in prevention of thrombosis. Br J Surg 1988;75:888-91. PMID: 2846113.
• 17. Biere SS, van Berge Henegouwen MI, Maas KW, Bonavina L, Rosman C, Garcia JR, et al. Minimally invasive versus open oesophagectomy for patients with oesophageal cancer: a multicentre, open-label, randomised controlled trial. Lancet 2012;379:1887-92. PMID: 22552194.
• 18. Bilimoria KY, Bentrem DJ, Merkow RP, Nelson H, Wang E, Ko CY, et al. Laparoscopic-assisted vs. open colectomy for cancer: comparison of short-term outcomes from 121 hospitals. J Gastrointest Surg 2008;12:2001-9. PMID: 18575941.
• 19. Blom JW, Osanto S, Rosendaal FR. High risk of venous thrombosis in patients with pancreatic cancer: a cohort study of 202 patients. Eur J Cancer. 2006 Feb;42(3):410-4. PubMed PMID: 16321518.
• 20. Borkgren-Okonek MJ, Hart RW, Pantano JE, Rantis PC Jr, Guske PJ, Kane JM Jr, et al. Enoxaparin thromboprophylaxis in gastric bypass patients: extended duration, dose stratification, and antifactor Xa activity. Surg Obes Relat Dis 2008;4:625-31. PMID: 18261965.
• 21. Borly L, Wille-Jørgensen P, Rasmussen MS. Systematic review of thromboprophylaxis in colorectal surgery -- an update. Colorectal Dis 2005;7:122-7. PMID: 15720347.
• 22. Bounameaux H, Huber O, Khabiri E, Schneider PA, Didier D, Rohner A. Unexpectedly high rate of phlebographic deep venous thrombosis following elective general abdominal surgery among patients given prophylaxis with low-molecular-weight heparin. Arch Surg 1993;128:326-8. PMID: 8382919.
• 23. Brandjes DP, ten Cate JW, Buller HR. Pre-surgical identification of the patient at risk for developing venous thromboembolism post-operatively. Acta Chir Scand Suppl 1990;556:18-21.PMID: 2288176.
• 24. Chandrasekaran S, Ariaretnam SK, Tsung J, Dickison D. Early mobilization after total knee replacement reduces the incidence of deep venous thrombosis. ANZ J Surg 2009;79:526-9. PMID: 19694660.
• 25. Collins R, Scrimgeour A, Yusuf S, Peto R. Reduction in fatal pulmonary embolism and venous thrombosis by perioperative administration of subcutaneous heparin. Overview of results of randomized trials in general, orthopedic, and urologic surgery. N Engl J Med 1988;318:1162-1173.
• ²⁶
  Comparison of a low molecular weight heparin and unfractionated heparin for the prevention of deep vein thrombosis in patients undergoing abdominal surgery. The European Fraxiparin Study (EFS) Group. Br J Surg. 1988;75:1058-63. PMID: 2905187.
• 27. Covey TH, Sherman L, Baue AE. Low-dose heparin in postoperative patients: a prospective, coded study. Arch Surg. 1975;110:1021-1026.
• 28. Croome KP, Yamashita MH. Laparoscopic vs open hepatic resection for benign and malignant tumors: An updated meta-analysis. Arch Surg 2010;145:1109-18. PMID: 21079101.
• 29. Dranitsaris G, Jelincic V, Choe Y. Meta-regression analysis to indirectly compare prophylaxis with dalteparin or enoxaparin in patients at high risk for venous thromboembolic events. Clin Appl Thromb Hemost 2012;18:233-42.
• 30. Dutia M, White RH, Wun T. Risk assessment models for cancer-associated venousthromboembolism. Cancer 2012;118:3468-76. PMID: 22086826.
• 31. Efficacy and safety of enoxaparin versus unfractionated heparin for prevention of deep vein thrombosis in elective cancer surgery: a double-blind randomized multicentre trial with venographic assessment. ENOXACAN Study Group. Br J Surg 1997;84:1099-103. PMID: 9278651
• 32. Egger B, Schmid SW, Naef M, Wildi S, Büchler MW. Efficacy and safety of weight-adapted nadroparin calcium vs. heparin sodium in prevention of clinically evident thromboembolic complications in 1,190 general surgical patients. Dig Surg 2000;17:602-609. PMID: 11155006.
• 33. Einstein MH, Pritts EA, Hartenbach EM. Venous thromboembolism prevention in gynecologic cancer surgery: a systematic review. Gynecol Oncol 2007;105:813-9. PMID: 17449089.
• 34. Fricker JP, Vergnes Y, Schach R, Heitz A, Eber M, Grunebaum L, et al. Low dose heparin versus low molecular weight heparin (Kabi 2165, Fragmin) in the prophylaxis of thromboembolic complications of abdominal oncological surgery. Eur J Clin Invest 1988;18:561-7. PMID: 2852111.
• 35. Gallus A, Cade J, Ockelford P, Hepburn S, Maas M, Magnani H, et al. Orgaran (Org 10172) or heparin for preventing venous thrombosis after elective surgery for malignant disease? A double-blind, randomised, multicentre comparison. ANZ-Organon Investigators' Group. Thromb Haemost 1993;70:562-7. PMID: 7509509.
• 36. Gallus AS, Hirsh J, O'Brien SE, McBride JA, Tuttle RJ, Gent M. Prevention of venous thrombosis with small, subcutaneous doses of heparin. JAMA. 1976; 235:1980-1982.
• 37. Gomes M, Ramacciotti E, Henriques AC, Araujo GR, Szultan LA, Miranda F Jr, Thethi I. Generic versus branded enoxaparin in the prevention of venous thromboembolism following major abdominal surgery: report of an exploratory clinical trial. Clin Appl Thromb Hemost 2011;17:633-9. PMID: 21949036.
• 38. Haas S, Schellong SM, Tebbe U, Gerlach HE, Bauersachs R, Melzer N, et al. Heparin based prophylaxis to prevent venous thromboembolic events and death in patients with cancer - a subgroup analysis of CERTIFY. BMC Cancer 2011;11:316. PMID: 21791091.
• 39. Hamad GG, Choban PS. Enoxaparin for thromboprophylaxis in morbidly obese patients undergoing bariatric surgery: findings of the prophylaxis against VTE outcomes in bariatric surgery patients receiving enoxaparin (PROBE) study. Obes Surg 2005;15:1368-74. PMID: 16354513.
• 40. Hammond J, Kozma C, Hart JC, Nigam S, Daskiran M, Paris A, Mackowiak JI. Rates of venous thromboembolism among patients with major surgery for cancer. Ann Surg Oncol. 2011 Nov;18(12):3240-7. Epub 2011 May 17. PubMed PMID: 21584837.
• 41. Hida K, Hasegawa S, Kinjo Y, Yoshimura K, Inomata M, Ito M, et al. Open versus laparoscopic resection of primary tumor for incurable stage IV colorectal cancer: a large multicenter consecutive patients cohort study. Ann Surg 2012;255:929-34. PMID: 22367445.
• 42. Ho YH, Seow-Choen F, Leong A, Eu KW, Nyam D, Teoh MK. Randomized, controlled trial of low molecular weight heparin vs. no deep vein thrombosis prophylaxis for major colon and rectal surgery in Asian patients. Dis Colon Rectum 1999;42:196-202. PMID: 10211496.
• 43. Jeong O, Ryu SY, Park YK, Kim YJ. The effect of low molecular weight heparin thromboprophylaxis on bleeding complications after gastric cancer surgery. Ann Surg Oncol 2010;17:2363-9. PMID: 20358302.
• 44. Joffe S. Drug prevention of postoperative deep venous thombosis: a comparative study of calcium heparinate and sodium pentosan polysulfate. Arch Surg. 1976;111:37-40.
• 45. Junqueira DR, Perini E, Penholati RR, Carvalho MG. Unfractionated heparin versus low molecular weight heparin for avoiding heparin-induced thrombocytopenia in postoperative patients. Cochrane Database Syst Rev 2012;9:CD007557. PMID: 22972111.
• 46. Kakkar VV, Balibrea JL, Martínez-González J, Prandoni P; CANBESURE Study Group. Extended prophylaxis with bemiparin for the prevention of venous thromboembolism after abdominal or pelvic surgery for cancer: the CANBESURE randomized study. J Thromb Haemost 2010;8:1223-9. PMID: 20456751.
• 47. Kakkar VV, Boeckl O, Boneu B, Bordenave L, Brehm OA, Brücke P, et al. Efficacy and safety of a low-molecular-weight heparin and standard unfractionated heparin for prophylaxis of postoperative venous thromboembolism: European multicenter trial. World J Surg 1997;21:2-8; discussion 8-9. PMID: 8943170.
• 48. Kakkar VV, Cohen AT, Edmonson RA, Phillips MJ, Cooper DJ, Das SK, et al. Low molecular weight versus standard heparin for prevention of venous thromboembolism after major abdominal surgery. The Thromboprophylaxis Collaborative Group. Lancet 1993;341:259-65. PMID: 8093915.
• 49. Kakkar VV, Corrigan TP, Fossard DP, Sutherland I, Thirwell J. Prevention of Fatal Postoperative pulmonary embolism by low doses of heparin. Reappraisal of results of international multicentre trial. Lancet 1977;1:567-9. PMID: 65660.
• 50. Kakkar VV, Djazaeri B, Fok J, Fletcher M, Scully MF, Westwick J. Low-molecular-weight heparin and prevention of postoperative deep vein thrombosis. Br Med J (Clin Res Ed) 1982;284:375-9. PMID:6800465.
• 51. Kakkos SK, Caprini JA, Geroulakos G, Nicolaides AN, Stansby GP, Reddy DJ. Combined intermittent pneumatic leg compression and pharmacological prophylaxis for prevention of venous thrombo-embolism in high-risk patients. Eur J Vasc Endovasc Surg 2009; 37:364-5. PMID: 19162515.
• 52. Kalfarentzos F, Stavropoulou F, Yarmenitis S, Kehagias I, Karamesini M, Dimitrakopoulos A, et al. Prophylaxis of venous thromboembolism using two different doses of low-molecular-weight heparin (nadroparin) in bariatric surgery: a prospective randomized trial. Obes Surg 2001;11:670-6.
• 53. Khorana AA, Connolly GC. Assessing risk of venous thromboembolism in the patient with cancer. J Clin Oncol 2009;27:4839-47. PMID: 19720906.
• 54. Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH. Frequency, risk factors, and trends for venous thromboembolism among hospitalized cancer patients. Cancer. 2007 Nov 15;110(10):2339-46. PubMed PMID: 17918266.
• 55. Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood 2008;111:4902-7. PMID: 18216292.
• 56. Khorana AA, Rao MV. Approaches to risk-stratifying cancer patients for venous thromboembolism. Thromb Res 2007;120 Suppl 2:S41-50. PMID: 18023712.
• 57. Kiil J, Kiil J, Axelsen F, Andersen D. Prophylaxis against postoperative pulmonary embolism and deep-vein thrombosis by low-dose heparin. Lancet. 1978; 1:1115-1116.
• 58. Kucher N, Koo S, Quiroz R, Cooper JM, Paterno MD, Soukonnikov B, et al. Electronic alerts to prevent venous thromboembolism among hospitalized patients. N Engl J Med 2005;352:969- 77. PMID: 15758007.
• 59. Kucher N, Leizorovicz A, Vaitkus PT, Cohen AT, Turpie AG, Olsson CG, et al. Efficacy and safety of fixed low-dose dalteparin in preventing venous thromboembolism among obese or elderly hospitalized patients: a subgroup analysis of the PREVENT trial. Arch Intern Med 2005;165:341-5. PMID: 15710801.
• 60. Lausen I, Jensen R, Jorgensen LN, Rasmussen MS, Lyng KM, Andersen M, et al. Incidence and prevention of deep venous thrombosis occurring late after general surgery: randomised controlled study of prolonged thromboprophylaxis. Eur J Surg 1998;164:657-63. PMID: 9728784.
• 61. Lee JH, Park do J, Kim HH, Lee HJ, Yang HK. Comparison of complications after laparoscopy-assisted distal gastrectomy and open distal gastrectomy for gastric cancer using the Clavien-Dindo classification. Surg Endosc 2012;26:1287-95. PMID: 22044981.
• 62. Leonardi MJ, McGory ML, Ko CY. The rate of bleeding complications after pharmacologic deep venous thrombosis prophylaxis: a systematic review of 33 randomized controlled trials. Arch Surg 2006;141:790-797.
• 63. Liang X, Hou S, Liu H, Li Y, Jiang B, Bai W, et al. Effectiveness and safety of laparoscopic resection versus open surgery in patients with rectal cancer: a randomized, controlled trial from China. J Laparoendosc Adv Surg Tech A 2011;21:381-5. PMID: 21395453.
• 64. Limmer J, Ellbrück D, Müller H, Eisele E, Rist J, Schütze F, et al. Prospective randomized clinical study in general surgery comparing a new low molecular weight heparin with unfractionated heparin in the prevention of thrombosis. Clin Investig 1994;72:913-9. PMID: 7894222.
• 65. Linke LC, Katthagen BD. Weight-based heparin dosing is more effective in the treatment of postoperative deep vein thrombosis. Arch Orthop Trauma Surg 1999;119:208-11. PMID: 10392521.
• 66. Lloyd GM, Kirby R, Hemingway DM, Keane FB, Miller AS, Neary P. The RAPID protocol enhances patient recovery after both laparoscopic and open colorectal resections. Surg Endosc 2010;24:1434-9. PMID: 20035353.
• 67. Louzada ML, Majeed H, Dao V, Wells PS. Risk of recurrent venous thromboembolism according to malignancy characteristics in patients with cancer-associated thrombosis: a systematic review of observational and intervention studies. Blood Coagul Fibrinolysis. 2011 Mar;22(2):86-91. Review. PubMed PMID: 21245746.
• 68. Lowe GD, Osborne DH, McArdle BM, Smith A, Carter DC, Forbes CD, et al. Prediction and selective prophylaxis of venous thrombosis in elective gastrointestinal surgery. Lancet 1982;1:409-12. PMID: 6121087.
• 69. Lyman GH, Khorana AK. Cancer, clots and consensus: new understanding of an old problem. J Clin Oncol. 2009;27:4821 - 4826.
• 70. Mamidanna R, Bottle A, Aylin P, Faiz O, Hanna GB. Short-term outcomes following open versus minimally invasive esophagectomy for cancer in England: a population-based national study. Ann Surg 2012;255:197-203. PMID: 22173202.
• 71. Mandalà M, Falanga A, Cremonesi M, Zaccanelli M, Floriani I, Viganò MG, Rosti A, Cazzaniga ME, Ferretti G, Cabiddu M, Barni S. The extension of disease is associated to an increased risk of venous thromboembolism (VTE) in patients with gastrointestinal (GI) carcinoma. Thromb Haemost. 2006 Apr;95(4):752-4. PubMed PMID: 16601855.
• 72. Marassi A, Balzano G, Mari G, D'Angelo SV, Della Valle P, Di Carlo V, D'Angelo A. Prevention of postoperative deep vein thrombosis in cancer patients. A randomized trial with low molecular weight heparin (CY 216). Int Surg 1993;78:166-70. PMID: 8394842.
• 73. McKay GD, Morgan MJ, Wong SK, Gatenby AH, Fulham SB, Ahmed KW, et al. Improved short-term outcomes of laparoscopic versus open resection for colon and rectal cancer in an area health service: a multicenter study. Dis Colon Rectum 2012;55:42-50. PMID: 22156866.
• 74. McLeod RS, Geerts WH, Sniderman KW, Greenwood C, Gregoire RC, Taylor BM, et al. Subcutaneous heparin versus low-molecular-weight heparin as thromboprophylaxis in patients undergoing colorectal surgery: results of the canadian colorectal DVT prophylaxis trial: a randomized, double-blind trial. Ann Surg 2001;233:438-44. PMID: 11224634.
• 75. Merkow RP, Bilimoria KY, McCarter MD, Cohen ME, Barnett CC, Raval MV, Caprini JA, Gordon HS, Ko CY, Bentrem DJ. Post-discharge venous thromboembolism after cancer surgery: extending the case for extended prophylaxis. Ann Surg. 2011 Jul;254(1):131-7. PubMed PMID: 21527843.
• 76. Meyer G, Marjanovic Z, Valcke J, Lorcerie B, Gruel Y, Solal-Celigny P, et al. Comparison of low-molecular-weight heparin and warfarin for the secondary prevention of venous thromboembolism in patients with cancer: a randomized controlled study. Arch Intern Med 2002;162:1729-35.
• 77. Mirnezami R, Mirnezami AH, Chandrakumaran K, Abu Hilal M, Pearce NW, Primrose JN, et al. Short- and long-term outcomes after laparoscopic and open hepatic resection: systematic review and meta-analysis. HPB (Oxford) 2011;13:295-308. PMID: 21492329.
• 78. Moussa OM, Rajaganeshan R, Abouleid A, Corless DJ, Slavin JP, Khan A, et al. Single-center comparative study of laparoscopic versus open colorectal surgery: a 2-year experience. Surg Laparosc Endosc Percutan Tech 2012;22:29-32. PMID: 22318056.
• 79. Neudecker J, Junghans T, Ziemer S, Raue W, Schwenk W. Prospective randomized trial to determine the influence of laparoscopic and conventional colorectal resection on intravasal fibrinolytic capacity. Surg Endosc 2003;17:73-7. PMID: 12364991.
• 80. Neudecker J, Klein F, Bittner R, Carus T, Stroux A, Schwenk W, et al. Short-term outcomes from a prospective randomized trial comparing laparoscopic and open surgery for colorectal cancer. Br J Surg 2009;96:1458-67. PMID: 19918852.
• 81. Nguyen KT, Marsh JW, Tsung A, Steel JJ, Gamblin TC, Geller DA. Comparative benefits of laparoscopic vs open hepatic resection: a critical appraisal. Arch Surg 2011;146:348-56. PMID: 21079109.
• 82. Nicolaides AN, Miles C, Hoare M, Jury P, Helmis E, Venniker R. Intermittent sequential pneumatic compression of the legs and thromboembolism-deterrent stockings in the prevention of postoperative deep venous thrombosis. Surgery 1983;94:21-5. PMID: 6857507.
• 83. Nilsson KR, Berenholtz SM, Garrett-Mayer E, Dorman T, Klag MJ, Pronovost PJ. Association between venous thromboembolism and perioperative allogeneic transfusion. Arch Surg. 2007 Feb;142(2):126-32; discussion 133. PubMed PMID: 17309963.
• 84. Nurmohamed MT, Verhaeghe R, Haas S, Iriarte JA, Vogel G, van Rij AM, et al. A comparative trial of a low molecular weight heparin (enoxaparin) versus standard heparin for the prophylaxis of postoperative deep vein thrombosis in general surgery. Am J Surg 1995;169:567-71. PMID: 7771617.
• 85. Nygren J, Soop M, Thorell A, Hausel J, Ljungqvist O; ERAS Group. An enhanced-recovery protocol improves outcome after colorectal resection already during the first year: a single-center experience in 168 consecutive patients. Dis Colon Rectum 2009;52:978-85. PMID: 19502866.
• 86. Ockelford PA, Patterson J, Johns AS. A double-blind randomized placebo controlled trial of thromboprophylaxis in major elective general surgery using once daily injections of a low molecular weight heparin fragment (Fragmin). Thromb Haemost 1989;62:1046-9. PMID: 2559484.
• 87. Pannucci CJ, Shanks A, Moote MJ, Bahl V, Cederna PS, Naughton NN, et al. Identifying patients at high risk for venous thromboembolism requiring treatment after outpatient surgery. Ann Surg 2012;255:1093-9. PMID: 22584630.
• 88. Perkins J, Beech A, Hands L. Vascular surgical society of Great Britain and Ireland: randomized controlled trial of heparin plus graduated compression stocking for the prophylaxis of deep venous thrombosis in general surgical patients. Br J Surg 1999; 86:701. PMID: 10361334.
• 89. Prandoni P, Lensing AW, Buller HR, et al. Deep-vein thrombosis and the incidence of subsequent symptomatic cancer. N Engl J Med. 1992;327:1128 1133.
• 90. Prophylactic efficacy of low-dose dihydroergotamine and heparin in postoperative deep venous thrombosis following intra-abdominal operations. J Vasc Surg. 1984;1:608-616.
• 91. Raschke RA, Reilly BM, Guidry JR, Fontana JR, Srinivas S. The weight-based heparin dosing nomogram compared with a "standard care" nomogram. A randomized controlled trial. Ann Intern Med 1993;119:874-81. PMID: 8214998.
• 92. Rasmussen A, Hansen PT, Lindholt J, Poulsen TD, Toftdahl DB, Gram J, et al. Venous thrombosis after abdominal surgery. A comparison between subcutaneous heparin and antithrombotic stockings, or both. J Med 1988;19:193-201. PMID: 2972790.
• 93. Rasmussen MS, Jorgensen LN, Wille-Jørgensen P, Nielsen JD, Horn A, Mohn AC, et al. Prolonged prophylaxis with dalteparin to prevent late thromboembolic complications in patients undergoing major abdominal surgery: a multicenter randomized open-label study. J Thromb Haemost 2006;4:2384-90. PMID: 16881934.
• 94. Reddy SK, Turley RS, Barbas AS, Steel JL, Tsung A, Marsh JW, Clary BM, Geller DA. Post-operative pharmacologic thromboprophylaxis after major hepatectomy: does peripheral venous thromboembolism prevention outweigh bleeding risks? J Gastrointest Surg 2011;15:1602-10. PMID: 21691924.
• 95. Reinke CE, Drebin JA, Kreider S, Kean C, Resnick A, Raper S, et al. Timing of preoperative pharmacoprophylaxis for pancreatic surgery patients: a venous thromboembolism reduction initiative. Ann Surg Oncol 2012;19:19-25. PMID: 21725687.
• 96. Rogers SO Jr, Kilaru RK, Hosokawa P, Henderson WG, Zinner MJ, Khuri SF. Multivariable predictors of postoperative venous thromboembolic events after general and vascular surgery: results from the patient safety in surgery study. J Am Coll Surg 2007;204:1211-21. PMID: 17544079.
• 97. Rostambeigi N, Greenlee SM, Huebner M, Farley DR. When is the best time to initiate peri-operative heparin therapy in general surgery patients? A risk-benefit dilemma. Am Surg 2011;77:1539-45. PMID: 22196671.
• 98. Sakon M, Kobayashi T, Shimazui T. Efficacy and safety of enoxaparin in Japanese patients undergoing curative abdominal or pelvic cancer surgery: results from a multicenter, randomized, open-label study. Thromb Res 2010;125:e65-70. PMID: 19919878.
• 99. Samama M, Bernard P, Bonnardot JP, Combe-Tamzali S, Lanson Y, Tissot E. Low molecular weight heparin compared with unfractionated heparin in prevention of postoperative thrombosis. Br J Surg 1988;75:128-31. PMID: 2832030.
• 100. Samama M, Combe S. Prevention of thromboembolic disease in general surgery with enoxaparin (Clexane). Acta Chir Scand Suppl 1990;556:91-5. PMID: 1963022.
• 101. Samama MM, Dahl OE, Quinlan DJ, Mismetti P, Rosencher N. Quantification of risk factors for venous thromboembolism: a preliminary study for the development of a risk assessment tool. Haematologica 2003;88:1410-21. PMID: 14687996.
• 102. Scholten DJ, Hoedema RM, Scholten SE. A comparison of two different prophylactic dose regimens of low molecular weight heparin in bariatric surgery. Obes Surg 2002;12:19-24. PMID: 11868291.
• 103. Short SS, Nasseri Y, Gangi A, Berel D, Fleshner P. Deep vein thrombosis prophylaxis increases perioperative surgical site infection in a prospective cohort of patients undergoing colorectal surgery. Am Surg 2011;77:1309-13. PMID: 22127076.
• 104. Simanek R, Vormittag R, Ay C, Alguel G, Dunkler D, Schwarzinger I, et al. High platelet count associated with venous thromboembolism in cancer patients: results from the Vienna Cancer and Thrombosis Study (CATS). J Thromb Haemost 2010;8:114-20. PMID: 19889150.
• 105. Simonneau G, Laporte S, Mismetti P, Derlon A, Samii K, Samama CM, Bergman JF; FX140 Study Investigators. A randomized study comparing the efficacy and safety of nadroparin 2850 IU (0.3 mL) vs. enoxaparin 4000 IU (40 mg) in the prevention of venous thromboembolism after colorectal surgery for cancer. J Thromb Haemost 2006;4:1693-700. PMID: 16796710.
• 106. Singh K, Podolsky ER, Um S, Saba S, Saeed I, Aggarwal L, et al. Evaluating the safety and efficacy of BMI-based preoperative administration of low-molecular-weight heparin in morbidly obese patients undergoing Roux-en-Y gastric bypass surgery. Obes Surg 2012;22:47-51. PMID: 21476124.
• 107. Stein PD, Beemath A, Meyers FA, Skaf E, Sanchez J, Olson RE. Incidence of venous thromboembolism in patients hospitalized with cancer. Am J Med. 2006 Jan;119(1):60-8. PubMed PMID: 16431186.
• 108. Stender MT, Frøkjaer JB, Larsen TB, Lundbye-Christensen S, Thorlacius-Ussing O. Preoperative plasma D-dimer is a predictor of postoperative deep venous thrombosis in colorectal cancer patients: a clinical, prospective cohort study with one-year follow-up. Dis Colon Rectum 2009;52:446-51. PMID: 19333044.
• 109. Stender MT, Nielsen TS, Frøkjaer JB, Larsen TB, Lundbye-Christensen S, Thorlacius-Ussing O. High preoperative prevalence of deep venous thrombosis in patients with colorectal cancer. Br J Surg. 2007 Sep;94(9):1100-3. PubMed PMID: 17440957.
• 110. Sugimachi K, Tajiri H, Kinjo N, Ikebe M, Wang H, Tanaka K, et al. Incidence and predictors of deep venous thrombosis after abdominal oncologic surgery: Prospective Doppler ultrasound screening. J Surg Res 2012. PMID: 22739045.
• 111. Teman NR, Silski L, Zhao L, Kober M, Urba SC, Orringer MB, Chang AC, Lin J, Reddy RM. Thromboembolic events before esophagectomy for esophageal cancer do not result in worse outcomes. Ann Thorac Surg. 2012 Oct;94(4):1118-25. doi: 10.1016/j.athoracsur.2012.05.109. Epub 2012 Aug 2. PubMed PMID: 22858275.
• 112. Tincani E, Piccoli M, Turrini F, Crowther MA, Melotti G, Bondi M. VideoBlaparoscopic surgery: is out-of-hospital thromboprophylaxis necessary? J ThrombBHaemost 2005;3:216-20.BPMID: 15670021.
• 113. Torngren S, Forsberg K. Concentrated or diluted heparin prophylaxis of postoperative deep venous thrombosis. Acta Chir Scand. 1978;144:283-288.
• 114. Törngren S. Low dose heparin and compression stockings in the prevention of postoperative deep venous thrombosis. Br J Surg 1980; 67:482-4. PMID: 6998538.
• 115. Trastulli S, Cirocchi R, Listorti C, Cavaliere D, Avenia N, Gullà N, et al. Laparoscopic vs open resection for rectal cancer: a meta-analysis of randomized clinical trials. Colorectal Dis 2012;14:e277-96. PMID: 22330061.
• 116. Trujillo-Santos J, Perea-Milla E, Jiménez-Puente A, Sánchez-Cantalejo E, del Toro J, Grau E, et al. Bed rest or ambulation in the initial treatment of patients with acute deep vein thrombosis or pulmonary embolism: findings from the RIETE registry. Chest 2005;127:1631-6. PMID: 15888839.
• 117. Tsutsumi K, Udagawa H, Kajiyama Y, Kinoshita Y, Ueno M, Nakamura T, et al. Pulmonary thromboembolism after surgery for esophageal cancer: its features and prophylaxis. Surg Today 2000;30:416-20. PMID: 10819476.
• 118. Tzeng CW, Katz MH, Fleming JB, Pisters PW, Lee JE, Abdalla EK, Curley SA, Vauthey JN, Aloia TA. Risk of venous thromboembolism outweighs post-hepatectomy bleeding complications: analysis of 5651 National Surgical Quality Improvement Program patients. HPB (Oxford). 2012 Aug;14(8):506-13. doi: 10.1111/j.1477-2574.2012.00479.x. Epub 2012 May 15. PubMed PMID: 22762398; PubMed Central PMCID: PMC3406347.
• 119. Varpe P, Huhtinen H, Rantala A, Grönroos J. Thromboprophylaxis following surgery for colorectal cancer - is it worthwhile after hospital discharge? Scand J Surg 2009;98:58-61.PMID: 19447743.
• 120. Verso M, Agnelli G, Barni S, Gasparini G, LaBianca R. A modified Khorana risk assessment score for venous thromboembolism in cancer patients receiving chemotherapy: the Protecht score. Intern Emerg Med 2012;7:291-2. PMID: 22547369.
• 121. Vijan SS, Ahmed KA, Harmsen WS, Que FG, Reid-Lombardo KM, Nagorney DM, et al. Laparoscopic vs open distal pancreatectomy: a single-institution comparative study. Arch Surg 2010;145:616-21. PMID: 20644122.
• 122. Vivarelli M, Zanello M, Zanfi C, Cucchetti A, Ravaioli M, Del Gaudio M, Cescon M, Lauro A, Montanari E, Grazi GL, Pinna AD. Prophylaxis for venous thromboembolism after resection of hepatocellular carcinoma on cirrhosis: is it necessary? World J Gastroenterol 2010;16:2146-50. PMID: 20440855.
• 123. Wang Q, Suo J, Jiang J, Wang C, Zhao YQ, Cao X. Effectiveness of fast-track rehabilitation vs conventional care in laparoscopic colorectal resection for elderly patients: a randomized trial. Colorectal Dis 2012;14:1009-13. PMID: 21985126.
• 124. Welsh FK, Tekkis PP, John TG, Rees M. Open liver resection for colorectal metastases: better short- and long-term outcomes in patients potentially suitable for laparoscopic liver resection. HPB (Oxford) 2010;12:188-94. PMID: 20590886.
• 125. White RH, Chew H, Wun T. Targeting patients for anticoagulant prophylaxis trials in patients with cancer: who is at highest risk? Thromb Res. 2007;120 Suppl 2:S29-40. Erratum in: Thromb Res. 2008;123(1):187-90. PubMed PMID: 18023711.
• 126. Wille-Jørgensen P, Hauch O, Dimo B, Christensen SW, Jensen R, Hansen B. Prophylaxis of deep venous thrombosis after acute abdominal operation. Surg Gynecol Obstet 1991;172:44-8. PMID: 1702235.
• 127. Wille-Jørgensen P, Ott P. Predicting failure of low-dose prophylactic heparin in general surgical procedures. Surg Gynecol Obstet 1990;171:126-30. PMID: 2382189.
• 128. Wille-Jørgensen P, Rasmussen MS, Andersen BR, Borly L. Heparins and mechanical methods for thromboprophylaxis in colorectal surgery. Cochrane Database Syst Rev 2003; (4):CD001217. PMID: 14583929.
• 129. Wille-Jørgensen P, Thorup J, Fischer A, Holst-Christensen J, Flamsholt R. Heparin with and without graded compression stockings in the prevention of thromboembolic complications of major abdominal surgery: a randomized trial. Br J Surg 1985;72:579-81. PMID: 4016545.
• 130. Wille-Jørgensen P. Prophylaxis of postoperative thromboembolism with a combination of heparin and graduated compression stockings.
• 131. Woller SC, Stevens SM, Jones JP, Lloyd JF, Evans RS, Aston VT, et al. Derivation and validation of a simple model to identify venous thromboembolism risk in medical patients. Am J Med 2011;124:947-954. PMID: 21962315.
• 132. Yang SS, Yu CS, Yoon YS, Yoon SN, Lim SB, Kim JC. Symptomatic venous thromboembolism in Asian colorectal cancer surgery patients. World J Surg. 2011 Apr;35(4):881-7. PubMed PMID: 21264469.

Publication Dates

• Publication in this collection
  07 Feb 2013
• Date of issue
  Dec 2012

History

• Received
  30 Sept 2012
• Accepted
  10 Nov 2012