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Gastrointestinal Surgery

Risk of Hematologic Malignant Neoplasms From Abdominopelvic Computed Tomographic Radiation in Patients Who Underwent Appendectomy

Educational Objective
To identify the extent to which abdominopelvic computed tomography radiation may be associated with future hematologic malignant neoplasm.

1 Credit CME

JAMA Surgery

Published Online: January 20, 2021

Original Investigation

Article Information and Disclosures

Kyung Hee Lee, MD, PhD^1,2;

Seungjae Lee, MS³;

Ji Hoon Park, MD, PhD^1,2,3;

Sung Soo Lee, MS¹;

Hae Young Kim, MD, PhD¹;

Won Jin Lee, MD, PhD⁴;

Eun Shil Cha, PhD⁴;

Kwang Pyo Kim, PhD⁵;

Woojoo Lee, PhD⁶;

Ji Yun Lee, MD⁷;

Kyoung Ho Lee, MD, PhD^1,2,3,8

Author Affiliations

¹Department of Radiology, Seoul National University Bundang Hospital, Gyeonggi-do, Korea
²Department of Radiology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Gyeonggi-do, Korea
³Department of Applied Bioengineering, Seoul National University Graduate School of Convergence Science and Technology, Seoul, Korea
⁴Department of Preventive Medicine, Korea University College of Medicine, Seoul, Korea
⁵Department of Nuclear Engineering, Kyung Hee University, Gyeonggi-do, Korea
⁶Department of Public Health Science, Seoul National University Graduate School of Public Health, Seoul, Korea
⁷Division of Hematology-Oncology, Department of Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, Korea
⁸Interdisciplinary Program in Bioengineering, Seoul National University, Seoul, Korea

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Key Points

Question Is there a risk of hematologic malignant neoplasms from abdominopelvic computed tomography (CT) radiation when reverse causation bias is controlled for by defining the reasons for CT scan?

Findings In this nationwide population-based cohort study that included 825 820 patients who underwent appendectomy for acute appendicitis, there was a substantial excess risk of hematologic malignant neoplasms in the CT-exposed group compared with the CT-unexposed group. The carcinogenic risk was most pronounced in patients aged 0 to 15 years.

Meaning In this study, perioperative abdominopelvic CT was associated with a higher incidence of hematologic malignant neoplasms.

Abstract

Importance Whether computed tomography (CT) radiation is truly carcinogenic remains controversial. Large epidemiological studies that purportedly showed an association between CT radiation and carcinogenesis were limited by confounding by indication and reverse causation, because the reasons for CT examination were unknown.

Objective To measure the risk of hematologic malignant neoplasms associated with perioperative abdominopelvic CT radiation among patients who underwent appendectomy for acute appendicitis.

Design, Setting, and Participants This nationwide population-based cohort study used the National Health Insurance Service claims database in South Korea to assess 825 820 patients who underwent appendectomy for appendicitis from January 1, 2005, to December 31, 2015, and had no underlying risk factors for cancer. Patients were divided into CT-exposed (n = 306 727) or CT-unexposed (n = 519 093) groups. The study was terminated on December 31, 2017, and data were analyzed from October 30, 2018, to September 27, 2020.

Exposures Perioperative abdominopelvic CT examination from 7 days before to 7 days after appendectomy.

Main Outcomes and Measures The primary outcome was the incidence rate ratio (IRR) of hematologic malignant neoplasms for both groups. The secondary outcomes were IRR of abdominopelvic organ cancers and IRR of all cancers. The lag period was 2 years for the primary outcome and 5 years for secondary outcomes. The IRRs were calculated using Poisson regression models with adjustment for age and sex.

Results Among the study population of 825 820 patients (52.9% male; median age, 28 [interquartile range, 15-41] years), hematologic malignant neoplasms developed in 323 patients in the CT-exposed group during 1 486 518 person-years and 500 patients in the CT-unexposed group during 3 422 059 person-years. For all hematologic malignant neoplasms, the IRR for the CT-exposed vs CT-unexposed group was 1.26 (95% CI, 1.09-1.45; P = .002). In terms of individual categories of hematologic malignant neoplasms, the CT-exposed group had an elevated risk only for leukemia (IRR, 1.40 [98.75% CI, 1.04-1.87, adjusted by Bonferroni correction]; P = .005). There was no between-group difference in incidence rate of abdominopelvic organ cancers (IRR, 1.07 [95% CI, 1.00-1.15]; P = .06) and that of all cancers (IRR, 1.04 [95% CI, 0.99-1.09]; P = .14).

Conclusions and Relevance This study controlled for reverse causation bias by defining the reasons for CT scan, and findings suggest that abdominopelvic CT radiation is associated with a higher incidence of hematologic malignant neoplasms. Efforts should be continued for judicious use of CT examinations.

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Article Information

Accepted for Publication: November 7, 2020.

Published Online: January 20, 2021. doi:10.1001/jamasurg.2020.6357

Corresponding Author: Ji Hoon Park, MD, PhD, Department of Radiology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do 13620, Korea (pjihoon79@gmail.com).

Author Contributions: Dr Kyung Hee Lee and Mr Seungjae Lee contributed equally as co–first authors. Dr Park had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Kyung Hee Lee, S. Lee, Park, Kyoung Ho Lee.

Acquisition, analysis, or interpretation of data: Kyung Hee Lee, S. Lee, Park, S. S. Lee, H. Kim, W. J. Lee, Cha, K. Kim, W. Lee, J. Y. Lee.

Drafting of the manuscript: Kyung Hee Lee, Park, S. S. Lee, H. Kim, K. Kim.

Critical revision of the manuscript for important intellectual content: Kyung Hee Lee, S. Lee, Park, W. J. Lee, Cha, W. Lee, J. Y. Lee, Kyoung Ho Lee.

Statistical analysis: Kyung Hee Lee, S. Lee, Park, S. S. Lee, K. Kim, W. Lee.

Obtained funding: Park.

Administrative, technical, or material support: Park.

Supervision: Kyung Hee Lee, S. Lee, Park, W. J. Lee, J. Y. Lee.

Conflict of Interest Disclosures: Dr Kyung Hee Lee reported receiving grants from the National Research Foundation of Korea funded by the Korea government outside the submitted work. Dr Park reported receiving grants from the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education and Seoul National University Bundang Hospital Research Fund. No other disclosures were reported.

Funding/Support: This research was supported by grant NRF-2018R1D1A1B07050976 for the Basic Science Research Program through the National Research Foundation of Korea from the Ministry of Education and grant 14-2018-008 from the Seoul National University Bundang Hospital Research Fund.

Role of the Funder/Sponsor: The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: Choonsik Lee, PhD, Division of Cancer Epidemiology and Genetics, National Cancer Institute, provided advice in improving the manuscript, for which he was not compensated.

AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
1.00 credit toward the CME [and Self-Assessment requirements] of the American Board of Surgery’s Continuous Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.