Evaluation of the validity of the double two-thirds rule for diagnosing hemangiosarcoma in dogs with nontraumatic hemoperitoneum due to a ruptured splenic mass: a systematic review

Ashley R. SchickDepartment of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA

Search for other papers by Ashley R. Schick in
Current site
Google Scholar
PubMed
Close
 DVM
and
Janet A. GrimesDepartment of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA

Search for other papers by Janet A. Grimes in
Current site
Google Scholar
PubMed
Close
 DVM, MS, DACVS-SA
View More View Less

Abstract

OBJECTIVE

To evaluate the validity of the double two-thirds rule for a diagnosis of splenic hemangiosarcoma in dogs with nontraumatic hemoperitoneum due to a ruptured splenic mass.

SAMPLE

Systematic literature review.

PROCEDURES

3 databases (PubMed, CAB abstracts, and World of Science) were searched in November 2020. Articles were included if data on dogs with nontraumatic hemoperitoneum due to a splenic mass were included and subsequent pathologic diagnosis could be determined.

RESULTS

In total, 2,390 unique articles were identified, with 66 articles meeting the criteria for full-text review and 14 articles included for analysis. A total of 1,150 dogs were evaluated, with 73.0% (840/1,150) of dogs being diagnosed with a malignant splenic lesion and 27.0% (310/1,150) being diagnosed with a benign splenic lesion. Of the malignancies, 87.3% (733/840) were hemangiosarcoma. Levels of evidence were low, and bias was high as most included studies were retrospective case series.

CLINICAL RELEVANCE

The double two-thirds rule should be refined when evaluating dogs with nontraumatic hemoperitoneum from a ruptured splenic mass, with more dogs being diagnosed with a malignancy and hemangiosarcoma specifically than the double two-thirds rule indicates. These findings may be useful in an emergency setting to guide owners on potential diagnoses for dogs with nontraumatic hemoperitoneum due to a ruptured splenic mass. However, there remains a portion of these dogs with benign conditions and nonhemangiosarcoma malignancies that may have a good long-term prognosis compared to dogs with hemangiosarcoma. Studies with higher levels of evidence, lower risks of bias, and large case numbers are needed in the literature.

Abstract

OBJECTIVE

To evaluate the validity of the double two-thirds rule for a diagnosis of splenic hemangiosarcoma in dogs with nontraumatic hemoperitoneum due to a ruptured splenic mass.

SAMPLE

Systematic literature review.

PROCEDURES

3 databases (PubMed, CAB abstracts, and World of Science) were searched in November 2020. Articles were included if data on dogs with nontraumatic hemoperitoneum due to a splenic mass were included and subsequent pathologic diagnosis could be determined.

RESULTS

In total, 2,390 unique articles were identified, with 66 articles meeting the criteria for full-text review and 14 articles included for analysis. A total of 1,150 dogs were evaluated, with 73.0% (840/1,150) of dogs being diagnosed with a malignant splenic lesion and 27.0% (310/1,150) being diagnosed with a benign splenic lesion. Of the malignancies, 87.3% (733/840) were hemangiosarcoma. Levels of evidence were low, and bias was high as most included studies were retrospective case series.

CLINICAL RELEVANCE

The double two-thirds rule should be refined when evaluating dogs with nontraumatic hemoperitoneum from a ruptured splenic mass, with more dogs being diagnosed with a malignancy and hemangiosarcoma specifically than the double two-thirds rule indicates. These findings may be useful in an emergency setting to guide owners on potential diagnoses for dogs with nontraumatic hemoperitoneum due to a ruptured splenic mass. However, there remains a portion of these dogs with benign conditions and nonhemangiosarcoma malignancies that may have a good long-term prognosis compared to dogs with hemangiosarcoma. Studies with higher levels of evidence, lower risks of bias, and large case numbers are needed in the literature.

Supplementary Materials

    • Supplementary Figure S1 (PDF 136 KB)
    • Supplementary Table S1 (PDF 138 KB)

Contributor Notes

Corresponding author: Dr. Grimes (jgrimes@uga.edu)
  • 1.

    Spangler WL, Culbertson MR. Prevalence, type, and importance of splenic diseases in dogs: 1,480 cases (1985–1989). J Am Vet Med Assoc. 1992;200(6):829834.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Wendelburg KM, O’Toole TE, McCobb E, Price LL, Lyons JA, Berg J. Risk factors for perioperative death in dogs undergoing splenectomy for splenic masses: 539 cases (2001–2012). J Am Vet Med Assoc. 2014;245(12):13821390.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Figueiredo RS, Muramoto C, Fontes TN, et al. Lesions in 224 spleens of splenectomized dogs and evaluation of alternative techniques for previous microscopic diagnosis. Pesqui Vet Bras. 2019;39(8):622629.

    • Search Google Scholar
    • Export Citation
  • 4.

    Schick AR, Hayes GM, Singh A, Mathews KG, Higginbotham ML, Sherwood JM. Development and validation of a hemangiosarcoma likelihood prediction model in dogs presenting with spontaneous hemoabdomen: the HeLP score. J Vet Emerg Crit Care (San Antonio). 2019;29(3):239245.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Burgess KE, Price LL, King R, et al. Development and validation of a multivariable model and online decision-support calculator to aid in preoperative discrimination of benign from malignant splenic masses in dogs. J Am Vet Med Assoc. 2021;258(12):13621371.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Clifford CA, Hughes D, Beal MW, et al. Plasma vascular endothelial growth factor concentrations in healthy dogs and dogs with hemangiosarcoma. J Vet Intern Med. 2001;15(2):131135.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Lamerato-Kozicki AR, Helm KM, Jubala CM, Cutter GC, Modiano JF. Canine hemangiosarcoma originates from hematopoietic precursors with potential for endothelial differentiation. Exp Hematol. 2006;34(7):870878.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Thamm DH, Kamstock DA, Sharp CR, et al. Elevated serum thymidine kinase activity in canine splenic hemangiosarcoma. Vet Comp Oncol. 2012;10(4):292302.

  • 9.

    Heishima K, Mori T, Ichikawa Y, et al. MicroRNA-214 and microRNA-126 are potential biomarkers for malignant endothelial proliferative diseases. Int J Mol Sci. 2015;16(10):2537725391. doi:10.3390/ijms161025377

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Heishima K, Mori T, Sakai H, et al. MicroRNA-214 promotes apoptosis in canine hemangiosarcoma by targeting the COP1-p53 axis. PLoS One. 2015;10(9):e0137361. doi:10.1371/journal.pone.0137361

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Grimes JA, Lourenço BN, Coleman AE, Rissi DR, Schmiedt CW. MicroRNAs are differentially expressed in the serum and renal tissues of cats with experimentally induced chronic kidney disease: a preliminary study. Am J Vet Res. 2022;83(5):426433.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Grimes JA, Prasad N, Levy S, et al. A comparison of microRNA expression profiles from splenic hemangiosarcoma, splenic nodular hyperplasia, and normal spleens of dogs. BMC Vet Res. 2016;12(1):272. doi: 10.1186/s12917-016-0903-5

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Ballegeer EA, Forrest LJ, Dickinson RM, Schutten MM, Delaney FA, Young KM. Correlation of ultrasonographic appearance of lesions and cytologic and histologic diagnoses in splenic aspirates from dogs and cats: 32 cases (2002–2005). J Am Vet Med Assoc. 2007;230(5):690696.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Ivancić M, Long F, Seiler GS. Contrast harmonic ultrasonography of splenic masses and associated liver nodules in dogs. J Am Vet Med Assoc. 2009;234(1):8894.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    O’Brien RT, Iani M, Matheson J, Delaney F, Young K. Contrast harmonic ultrasound of spontaneous liver nodules in 32 dogs. Vet Radiol Ultrasound. 2004;45(6):547553.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Fife WD, Samii VF, Drost WT, Mattoon JS, Hoshaw-Woodard S. Comparison between malignant and nonmalignant splenic masses in dogs using contrast-enhanced computed tomography. Vet Radiol Ultrasound. 2004;45(4):289297.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Jones ID, Lamb CR, Drees R, Priestnall SL, Mantis P. Associations between dual-phase computed tomography features and histopathologic diagnoses in 52 dogs with hepatic or splenic masses. Vet Radiol Ultrasound. 2016;57(2):144153.

    • Search Google Scholar
    • Export Citation
  • 18.

    Clifford CA, Pretorius ES, Weisse C, et al. Magnetic resonance imaging of focal splenic and hepatic lesions in the dog. J Vet Intern Med. 2004;18(3):330338.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Mallinckrodt MJ, Gottfried SD. Mass-to-splenic volume ratio and splenic weight as a percentage of body weight in dogs with malignant and benign splenic masses: 65 cases (2007–2008). J Am Vet Med Assoc. 2011;239(10):13251327.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Mullin C, Clifford CA. Miscellaneous tumors. In: Vail DM, Thamm DH, Liptak JM, eds. Withrow & MacEwen’s Small Animal Clinical Oncology. 6th ed. Elsevier Saunders; 2020:773778.

    • Search Google Scholar
    • Export Citation
  • 21.

    Stewart SD, Ehrhart EJ, Davies R, Khanna C. Prospective observational study of dogs with splenic mass rupture suggests potentially lower risk of malignancy and more favourable perioperative outcomes. Vet Comp Oncol. 2020;18(4):811817.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    Hammond TN, Pesillo-Crosby SA. Prevalence of hemangiosarcoma in anemic dogs with a splenic mass and hemoperitoneum requiring a transfusion: 71 cases (2003–2005). J Am Vet Med Assoc. 2008;232(4):553558.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Aronsohn MG, Dubiel B, Roberts B, Powers BE. Prognosis for acute nontraumatic hemoperitoneum in the dog: a retrospective analysis of 60 cases (2003–2006). J Am Anim Hosp Assoc. 2009;45(2):7277.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24.

    Fleming J, Giuffrida MA, Runge JJ, et al. Anatomic site and etiology of hemorrhage in small versus large dogs with spontaneous hemoperitoneum. Vet Surg. 2018;47(8):10311038.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Cleveland MJ, Casale S. Incidence of malignancy and outcomes for dogs undergoing splenectomy for incidentally detected nonruptured splenic nodules or masses: 105 cases (2009–2013). J Am Vet Med Assoc. 2016;248(11):12671273.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26.

    Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372(71):n71. doi:10.1136/bmj.n71

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Oxford Centre for Evidence-Based Medicine: levels of evidence. University of Oxford Nuffield Department of Primary Care Health Sciences. Accessed August 14, 2021. https://www.cebm.ox.ac.uk/resources/levels-of-evidence/oxford-centre-for-evidence-based-medicine-levels-of-evidence-march-2009

    • Search Google Scholar
    • Export Citation
  • 28.

    Serrano G, Charalambous M, Devriendt N, de Rooster H, Mortier F, Paepe D. Treatment of congenital extrahepatic portosystemic shunts in dogs: a systematic review and meta-analysis. J Vet Intern Med. 2019;33(5):18651879.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Higgins J, Thomas J, Chandler J, et al. Cochrane Handbook for Systematic Reviews of Interventions. The Cochrane Collaboration; 2022. Accessed August 14, 2021. https://training.cochrane.org/handbook

    • Search Google Scholar
    • Export Citation
  • 30.

    Corbin EE, Cavanaugh RP, Schwartz P, Zawadzki KI, Donovan T. Splenomegaly in small-breed dogs: 45 cases (2005–2011). J Am Vet Med Assoc. 2017;250(10):11481154.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31.

    Davies O, Taylor AJ. Refining the “double two-thirds” rule: genotype-based breed grouping and clinical presentation help predict the diagnosis of canine splenic mass lesions in 288 dogs. Vet Comp Oncol. 2020;18(4):548558.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32.

    Fernandez S, Lang JM, Maritato KC. Evaluation of nodular splenic lesions in 370 small-breed dogs (<15 kg). J Am Anim Hosp Assoc. 2019;55(4):201209.

  • 33.

    Johnson KA, Powers BE, Withrow SJ, Sheetz MJ, Curtis CR, Wrigley RH. Splenomegaly in dogs. Predictors of neoplasia and survival after splenectomy. J Vet Intern Med. 1989;3(3):160166.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34.

    Levinson JG, Bouma JL, Althouse GC, Rieser TM. Prevalence of malignancy when solitary versus multiple lesions are detected during abdominal ultrasonographic examination of dogs with spontaneous hemoperitoneum: 31 cases (2003–2008). J Vet Emerg Crit Care (San Antonio). 2009;19(5):496500.

    • Search Google Scholar
    • Export Citation
  • 35.

    Marino DJ, Matthiesen DT, Fox PR, Lesser MB, Stamoulis ME. Ventricular arrhythmias in dogs undergoing splenectomy: a prospective study. Vet Surg. 1994;23(2):101106.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36.

    Sherwood JM, Haynes AM, Klocke E, et al. Occurrence and clinicopathologic features of splenic neoplasia based on body weight: 325 dogs (2003–2013). J Am Anim Hosp Assoc. 2016;52(4):220226.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37.

    Vnuk D, Gusak V, Schwendenwein I, Haas BM, Musulin A, Maticic D. Clinical characteristics and outcomes in 43 dogs with splenic masses of different origin. Wien Tierarztl Monatsschr. 2014;101(11):273280.

    • Search Google Scholar
    • Export Citation
  • 38.

    Prymak C, McKee LJ, Goldschmidt MH, Glickman LT. Epidemiologic, clinical, pathologic, and prognostic characteristics of splenic hemangiosarcoma and splenic hematoma in dogs: 217 cases (1985). J Am Vet Med Assoc. 1988;193(6):706712.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39.

    Herman EJ, Stern AW, Fox RJ, Dark MJ. Understanding the efficiency of splenic hemangiosarcoma diagnosis using Monte Carlo simulations. Vet Pathol. 2019;56(6):856859.

    • PubMed
    • Search Google Scholar
    • Export Citation

Advertisement