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Appendix removal associated with development of Parkinson’s disease

AppendixPatients who had their appendix removed were more likely to develop Parkinson's disease than those whose appendix remained in place, according to the largest study to address the relationship between the two conditions. The retrospective study involving more than 62m patient records from 26 health systems was presented at Digestive Disease Week (DDW) 2019.

"Recent research into the cause of Parkinson's has centred around alpha synuclein, a protein found in the gastrointestinal tract early in the onset of Parkinson's," said Dr Mohammed Z Sheriff, lead author of the study and a physician at Case Western Reserve University/University Hospitals Cleveland Medical Centre. "This is why scientists around the world have been looking into the gastrointestinal tract, including the appendix, for evidence about the development of Parkinson's."

Previous findings on appendectomies and Parkinson's have been inconsistent, with some studies showing no relationship and a recent study from Europe showing patients who still had their appendix were more likely to develop Parkinson's. This contradiction prompted Sheriff and colleagues at the Digestive Health Institute, Case Western Reserve University to seek answers to the question using US data from an Ohio-based electronic health records company that draws data from 26 major integrated health systems.

Researchers analysed electronic health records representing more than 62.2m patients and identified those who had appendectomies and were diagnosed with Parkinson's disease at least six months later.

They found that among 488,190 patients who had undergone appendectomies, 4,470, or .92%, went on to develop Parkinson's. Of the remaining 61.7m patients without appendectomies, they identified only 177,230, or .29%, who developed the disease. According to this analysis, patients who had an appendectomy were more than three times as likely to develop Parkinson's than those who had not.

Researchers found similar risk levels across all age groups, regardless of gender or race. Other than the six-month washout period programmed into their initial query of the database, researchers could not tell from the de-identified records exactly how much time passed after the appendectomy until Parkinson's was diagnosed.

"This research shows a clear relationship between the appendix, or appendix removal, and Parkinson's disease, but it is only an association," Sheriff said. "Additional research is needed to confirm this connection and to better understand the mechanisms involved."

Introduction: Aggregated alpha synuclein, a pathologic feature of Parkinson's disease, has been found to be present in enteric neurons. As these aggregated proteins appear in the gastrointestinal tract early in the onset of the Parkinson's disease, the GI tract may have a role in the development of disease. There has been conflicting reports on whether appendectomies increase the risk of Parkinson's disease. To this date, there is a lack of large-scale epidemiological data of this phenomenon in the US population.
Aims and Methods: The aim of this study was to investigate if appendectomies increase the risk of Parkinson's disease, in a large population based commercial database. The database used was Explorys Inc. (Cleveland, OH, USA) which contains electronic health records from 26 major integrated US healthcare systems. We identified patients who underwent appendectomies and those who were diagnosed with Parkinson's disease based on Systemized Nomenclature of Medicine – Clinical Terms. We chose a washout period of 6 months to the development of Parkinson's disease after appendectomies. We compared the prevalence of Parkinson's disease in the general population to those with appendectomies.
Results: Of the 62,218,050 in the database, we identified 488,190 patients who underwent appendectomies. A total of 4470 cases of Parkinson's disease were observed in patients with appendectomies, and 177,230 cases of Parkinson's disease in patients without appendectomies. The overall Relative Risk (RR) of developing Parkinson's disease in patients after appendectomies was 3.19, 95% CI 3.10 to 3.28; p<0.0001 compared to those who did not undergo the procedure. Patients aged 18-64 (RR 4.27, 95% CI 3.99 to 4.57, p<0.0001) and those aged ≥ 65 (RR 2.20, 95% CI 2.13 to 2.27, p<0.0001) both had an increased risk of developing Parkinson's disease. The gender prevalence and race based prevalence are described in Table 1. As demonstrated, Caucasians, African Americans, and Asians were at an increased risk of Parkinson's disease after appendectomies. The prevalence distribution with age is demonstrated in Figure 1.
Conclusion: Appendectomies increase the risk of Parkinson's disease in this large, population based, epidemiological study. This increase in risk occurs over all age groups, and regardless of gender or race. One limitation of the study to note is while a washout period was conducted, the time after appendectomy to the development of PD cannot be determined from the database.

Mohammed Z Sheriff, Emad Mansoor, Gregory S Cooper

[link url=""]The Society for Surgery of the Alimentary Tract Digestive Disease Week material[/link]
[link url=""]The Society for Surgery of the Alimentary Tract Digestive Disease Week abstract[/link]

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