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Current Issue

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Liver, Part III

Vol. 46, No. 5, 2020

  • Hepatocellular Carcinoma

  • Cholangiocarcinoma.

  • Primary Sarcoma of the Liver

  • Liver Transplantation

  • Variceal Bleeding Management

Featured Commentary

The online formats of SRGS include access to What You Should Know (WYSK): commentaries on articles published recently in top medical journals. These commentaries, written by practicing surgeons and other medical experts, focus on the strengths and weaknesses of the research, as well as on the articles' contributions in advancing the field of surgery.

Below is a sample of one of the commentaries published in the current edition of WYSK.


Kuczmik W, Wysokinski WE, Macedo T, et al. Calf vein thrombosis outcomes comparing anticoagulation and serial ultrasound imaging management strategies. Mayo Clin Proc. 2021;96(5):1184-1192. doi:10.1016/j.mayocp.2021.01.024

Commentary by: Vina Y. Chhaya, MD, MPH; James D. Greenwood, MD; and Melina R. Kibbe, MD, FACS

Distal deep vein thrombosis (DVT) is defined as involving the axial veins of the calf, which include the posterior tibial, peroneal, and/or anterior tibial veins, without thrombus extension into the popliteal vein. Some clinicians also include the muscular veins of the calf, the soleal and gastrocnemius veins, in this definition.1,2 Isolated symptomatic distal DVT represents 20 to 50 percent of all diagnosed lower extremity DVTs, and if untreated, about 15 percent will extend into the proximal veins within two weeks.3,4 The disease burden of distal DVT is high, with 300,000 cases diagnosed annually in the United States and an associated one-year all-cause mortality of 4.6 per 100-person years.2,4,5 The ninth edition of the CHEST guidelines published in 2012 recommends serial imaging of the deep veins for two weeks in patients diagnosed with acute distal DVT without severe symptoms or risk factors and anticoagulation in patients with severe symptoms or risk factors.3 Management of distal DVT remains controversial as these guidelines are based on weak and low-quality evidence (Grade 2C).3 Given that current guidelines result in variable management and that observational studies report the benefits of anticoagulation, Kuczmik et al. sought to elucidate the progression of distal DVT based on management strategy.2,6

All patients from a single vascular ultrasound center with imaging confirmed isolated distal DVT from January 2016 to August 2018 were included (n = 483) in the retrospective observational cohort analysis published by Kuczmik et al. Patients were managed with anticoagulation (n = 399) or serial ultrasound surveillance (n = 84). Outcomes were venous thromboembolism (VTE) recurrence, stratified by original thrombus propagation, pulmonary embolus (PE), or new DVT, as well as major and nonmajor bleeding. Risk factors associated with a prothrombotic state were disparate between the two treatment groups. Patients in the surveillance group were more likely to have had a recent hospitalization. In contrast, patients in the anticoagulation group were younger, had a family history of VTE, and had known thrombophilia. History of active cancer or metastatic disease was evenly distributed between groups. This study determined that in those patients receiving anticoagulation, DVT propagation was lower (2.8% vs. 8.3%, p = 0.01), VTE recurrence was not statistically significantly different (4.8% vs. 6%, p = 0.78), and there was no statistically significant difference in major or nonmajor bleeding events or death.

A strength of this cohort study is that it included 483 patients to study distal DVT progression by directly comparing the recommended management strategies of ultrasound surveillance and anticoagulation. The data collection also included detail on the extent of distal DVT propagation beyond the popliteal vein, which is not often reported in other studies. Patients followed with ultrasound had propagation of distal DVT within 13 days on average, prior corroborating studies that determined propagation would occur within two weeks. Patients were also followed up over a longer period to better understand the length of time to PE or DVT recurrence.

While providing valuable data on management strategies affecting the propagation of distal DVT, this study has several notable limitations. First, it is a single-center retrospective cohort study to clarify the role of ultrasound surveillance in the management of distal DVT. Still, there are no data on patients presenting symptoms or indications for the initial ultrasound. Thus, allocation to each of the two treatment groups is likely biased. Second, the authors do not state the location of the initial distal DVT and whether the axial or muscular tributaries are involved, which is notable because studies have shown differences in propagation and recurrence rates between the two. Third, the authors do not state how often ultrasound imaging was obtained during the follow-up period or how many patients' ultrasound was successfully obtained. Fourth, no data is collected on risk factors for thrombus extension, such as initial distal DVT size and length or D-dimer. Patients who had DVT propagation or VTE recurrence are not further stratified by any risk factors to assess if they received appropriate treatment based on current guidelines. Finally, the authors conclude that there is no increased bleeding risk in patients receiving anticoagulation. Still, they present no data on patient compliance with anticoagulation or the etiology of major and clinically relevant nonmajor bleeding despite specific criteria defined in the methods section.

Prior studies refute the data presented by Kuczmik and coauthors.4,7,8 The CACTUS study, a randomized, double-blinded, placebo-controlled trial, concluded that patients receiving LMWH vs. placebo for distal DVT have a higher risk of major or clinically relevant nonmajor bleeding with a risk difference of 4.1 (95% CI: 0.4-9.2, p = 0.03).7 This study also showed no benefit of anticoagulation in low-risk outpatients with symptomatic distal DVT on thrombus extension or VTE.7 The ACT project compared anticoagulation with LMWH transitioned to warfarin vs. over-the-counter pain medication for patients diagnosed with symptomatic distal DVT.8 They determined there were no major bleeding episodes and a non-statistically significant absolute risk reduction of 8.6 for popliteal thrombus extension in those patients receiving anticoagulation (95%CI: -3.5-23.1, p = 0.24).8 While the ACT project only enrolled 70 patients to establish the feasibility of conducting an RCT to study anticoagulation in distal DVT, it collected detailed data on symptoms, risk factors, and medication compliance measured by INR level. Analysis from a prospective observational cohort reported data on 2,145 patients with distal DVT and showed that while >90% were treated with anticoagulation, there was a decreased risk of major bleeding complications compared to patients with proximal DVT.4

Thus, while Kuczmik et al. conclude that anticoagulation decreases rates of thrombus extension and VTE recurrence in patients with distal DVT without increased bleeding risk, their retrospective cohort data does not change the current management strategy of distal DVT given the limitations that exist with the study. What is needed to address how best to treat patients with distal DVT are robust, well-controlled, prospective multicenter randomized clinical trials. Further, given that the CHEST guidelines are now nine years old, it is time for the American College of Chest Physicians to re-evaluate current published literature and update the guidelines to include the best data available.

References

  1. Robert-Ebadi H, Righini M. Should we diagnose and treat distal deep vein thrombosis?. Hematology Am Soc Hematol Educ Program. 2017;2017(1):231-236. doi:10.1182/asheducation-2017.1.231
  2. Fleck D, Albadawi H, Wallace A, Knuttinen G, Naidu S, Oklu R. Below-knee deep vein thrombosis (DVT): diagnostic and treatment patterns. Cardiovasc Diagn Ther. 2017;7(Suppl 3):S134-S139. doi:10.21037/cdt.2017.11.03
  3. Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines [published correction appears in Chest. 2012 Dec;142(6):1698-1704]. Chest. 2012;141(2 Suppl):e419S-e496S. doi:10.1378/chest.11-2301
  4. Schellong SM, Goldhaber SZ, Weitz JI, et al. Isolated Distal Deep Vein Thrombosis: Perspectives from the GARFIELD-VTE Registry [published correction appears in Thromb Haemost. 2019 Oct;119(10):e1]. Thromb Haemost. 2019;119(10):1675-1685. doi:10.1055/s-0039-1693461
  5. Chopard R, Albertsen IE, Piazza G. Diagnosis and Treatment of Lower Extremity Venous Thromboembolism: A Review. JAMA. 2020;324(17):1765-1776. doi:10.1001/jama.2020.17272
  6. Utter GH, Dhillon TS, Salcedo ES, et al. Therapeutic Anticoagulation for Isolated Calf Deep Vein Thrombosis. JAMA Surg. 2016;151(9):e161770. doi:10.1001/jamasurg.2016.1770
  7. Horner D, Hogg K, Body R, Nash MJ, Baglin T, Mackway-Jones K. The anticoagulation of calf thrombosis (ACT) project: results from the randomized controlled external pilot trial. Chest. 2014;146(6):1468-1477. doi:10.1378/chest.14-0235
Recommended Reading

The SRGS Recommended Reading List is a summary of the most pertinent articles cited in each issue; the editor has carefully selected a group of current, classic, and seminal articles for further study in certain formats of SRGS. The citations below are linked to their abstracts on PubMed, and free full texts are available where indicated.

SRGS has obtained permission from journal publishers to reprint these articles. Copying and distributing these reprints is a violation of our licensing agreement with these publishers and is strictly prohibited.

Khan AS, Dageforde LA. Cholangiocarcinoma. Surg Clin North Am. Apr 2019;99(2):315-335. doi:10.1016/j.suc.2018.12.004

Article summary: Khan and Dageforde provided a useful review of the biology, diagnosis, and management of cholangiocarcinoma, a rare but important liver malignancy.

Maynard E. Liver Transplantation: Patient Selection, Perioperative Surgical Issues, and Expected Outcomes. Surg Clin North Am. Feb 2019;99(1):65-72.

Article summary: This is a clearly written and informative review of surgical issues relevant to the management of patients who are candidates for liver transplantation.

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