Cohort studycited by the Tayebat archivefull text checked A-ORG-05 in-depth review

Appendix removal and bowel cancer

Risk of Gastrointestinal Cancers among Patients with Appendectomy: A Large-Scale Swedish Register-Based Cohort Study during 1970-2009.

Overview

Song H et al.. PLoS One 2016 · PMID 26959234 · DOI 10.1371/journal.pone.0151262

No increased risk of stomach, colon or rectal cancer after appendix removal.

Does the study support the specific claim? No · Methodological quality: moderate

Original publication

Plain-language summary

Study explained simply

What did the researchers want to find out?: Cancer risk
How was the study done?: Register
How many people, animals or samples were studied?: 480,382
What was actually found?: No excess
How large was the observed effect?: SIR EAC 1.32
What do the results mean in everyday life?: Appendectomy did not raise most GI cancers
What are the study's limitations?: SIR design
What does it say about Elawady's specific claim?: Contradicts archive summary
Do the results apply to Germany and Europe?: European
What can explicitly not be concluded from this study?: Small risks

Scientific in-depth review

1. Full reference

Authors: Song H, Abnet CC, Andrén-Sandberg Å, Chaturvedi AK, Ye W
Journal: PLoS One
Year: 2016
Identifier: PMID 26959234 DOI 10.1371/journal.pone.0151262 · PMC4784880
Verification: verified – PubMed E-utilities efetch, 2026-10-25
Retracted: no
Corrections: none
Extent checked: full text
Conflicts of interest and funding: Authors declare no competing interests. No funding statement in the full-text file.

2. Research question

GI cancer risk after appendectomy

3. Study design and population

Study design: Cohort study – Nationwide register-based cohort (Swedish National Patient Register linked to Cancer, Death and Emigration Registers) with standardized incidence ratios vs the general Swedish population; plus incidence-trend analysis 1987-2009
Population: All patients born before 2003 with appendectomy in Sweden 1970-2009 (mean age 32.5 years; 54.7% women); 327,496 appendicitis, 152,886 other diagnoses (negative or incidental appendectomy)
Country: Sweden
Period: 1970-2009
Sample size: 501,160 identified; 480,382 eligible after excluding 20,778 with conflicting dates; 269,185 for 1987-2009 incidence trends
Inclusion and exclusion criteria: Appendectomy codes 1970-2009; excluded conflicting records and, per sub-cohort, prior diagnosis of the respective cancer; first year of follow-up excluded (reverse causation/detection)

4. Methods and endpoints

Exposure / intervention: Appendectomy
Comparator: General population
Endpoints: Oesophageal (adenocarcinoma, squamous-cell), gastric (cardia, non-cardia), colon (right, left) and rectal cancer; incidence of appendectomy
Statistical methods: SIRs (observed/expected, standardized for age, sex, calendar period) with Poisson 95% CIs; stratification by diagnosis, sex, age, follow-up duration; Poisson trend tests; sensitivity analysis restricted to 1987-2009; lung and liver cancer SIRs as proxies for smoking/alcohol confounding

5. Actual results

Results: Mean follow-up 18.6 years. Appendectomy incidence fell from 189.3 to 105.6 per 100,000 (annual decrease 2.5%, 95% CI 2.0-3.0%); in ages 0-19 from 236.2 to 96.4 per 100,000; negative appendectomy fell to 5 per 100,000 in 2009; perforation ratio constant (18-23%). SIRs (first year excluded): oesophageal adenocarcinoma 1.32 (1.09-1.58; 118 cases), oesophageal squamous-cell 0.79 (0.65-0.95), gastric 1.00 (0.93-1.07), colon 1.03 (0.99-1.07), rectum 0.98 (0.93-1.04). By time since surgery: cardia cancer 1.63 (1.12-2.31) at 1-4 years only; right colon 1.15 (1.05-1.26) at 5-14 years; oesophageal adenocarcinoma 1.50 (1.06-2.07) at >=25 years. Proxy cancers: lung 1.03 (0.98-1.09), liver 0.84 (0.70-0.98).
Absolute risks: Observed case counts only (e.g. 118 oesophageal adenocarcinomas, 2473 colon cancers, 1280 rectal cancers); no absolute risk differences reported.
Authors' conclusion: Appendectomy incidence in Sweden decreased 1987-2009; no excess gastric, colon or rectal cancer risk; possible alteration of oesophageal cancer risks (likely confounded, e.g. by obesity).

6. Strengths

Nationwide, very large cohort with long follow-up (mean 18.6 years)
Complete cancer and censoring registers
One-year lag to limit reverse causation
Proxy-cancer analysis for smoking/alcohol confounding
Sensitivity analysis on fully nationwide period

7. Weaknesses

SIR comparison with general population; no adjustment for BMI, smoking, diet, socioeconomic status (authors)
Surveillance/detection bias (authors; e.g. early cardia cancer excess)
Patient Register coverage incomplete before 1987
Many stratified tests without multiplicity correction
No absolute risk estimates

8. Risk of bias

Orienting tool: ROBINS-E
Type of assessment: structured assessment based on the full text by a single reviewer (no formal double review)
Full formal assessment: no
Overall risk of bias: high
Rationale: Downgraded from some_concerns: the SIR design cannot control for lifestyle confounders, so the small positive/negative signals (oesophageal cancers) are not interpretable causally. The main null findings for gastric and colorectal cancer are unlikely to be reversed by such confounding. Structured single-reviewer judgement from full text; a formal assessment would require two independent reviewers and a protocol.

8. Risk of bias
Domain	Judgement	Rationale
Confounding	high	Only age, sex and calendar period standardized; no data on obesity, smoking, alcohol, SES; authors attribute the oesophageal signals to likely confounding.
Exposure measurement	low	Surgical procedure codes from national register.
Selection of participants	some concerns	Register coverage <100% before 1987; 20,778 records excluded for conflicting dates.
Post-exposure interventions	not applicable	Not relevant for this question.
Missing data	low	Complete register follow-up.
Outcome measurement	low	Cancer Register completeness 98%; surveillance bias possible early after surgery.
Selection of reported result	some concerns	Multiple strata and subtypes reported without correction; isolated significant SIRs.

Full-text review (25 October 2026): Added cohort derivation, follow-up (18.6 y), all SIRs incl. subtypes and time strata, incidence trends by age and diagnosis, proxy-cancer analysis, COI; bias downgraded to high (no confounder adjustment in SIR design).

9. Assessment of the statistical interpretation

Precise null SIRs for gastric, colon and rectal cancers; the oesophageal adenocarcinoma excess (SIR 1.32) shows no dose-time trend and is plausibly confounded by obesity; the opposite direction for squamous-cell carcinoma supports chance/confounding rather than a causal effect.

10. Relevance to the specific claim

Contradicts C-ORG-16 for appendectomy.

11. Independent contrary findings

12. Transferability to Germany and Europe

European.

13. Overall methodological judgement

Reassuring null finding for gastric and colorectal cancer after appendectomy, cited by the archive itself; it also documents a strong decline of appendectomy and negative appendectomy in Sweden.

Multidimensional assessment
Multidimensional assessment
Authenticity of the source	verified
Methodological quality	moderate
Risk of bias	high
Precision of results	high
Directness	direct
Reproducibility	unknown
Consistency with the overall evidence	consistent
Regional transferability	high
Adequacy of the interpretation (by the archive)	not applicable

14. Open questions

Absolute risks; confounder-adjusted comparisons (sibling or matched designs); effect on microbiome-related outcomes.

15. Linked fact checks

The appendix is not vestigial: Andersson 2001 'proves' an immune function because appendectomy for inflammation before age 20 is linked to lower ulcerative colitis risk. – Studies contradicting or limiting the claim
Long-term registry data link removal of tonsils, appendix, gallbladder, uterus, ovaries and spleen to higher rates of respiratory disease, autoimmunity, cardiovascular events, gastrointestinal cancers and dementia; each organ does work the body never fully replaces. – Studies contradicting or limiting the claim
The appendix (like tonsils and adenoids) is removed far too readily from early childhood onward. – Studies with mixed or unclear results

Use by the Tayebat archive

Note: according to the archive, the studies were compiled by the archive operators. Whether Dr. Elawady himself cited this study is not established.

What the archive says about the study: Listed in the archive bibliography only; the archive gives no specific interpretation.
A. What was actually studied?: GI cancer after appendectomy
B. What did the authors find?: No excess risk except marginal EAC
C. What conclusions do the authors themselves draw?: No excess
D. What does the archive derive from it?: Not used in narrative.
E. Is this derivation scientifically justified?: This archive-cited study largely contradicts the summary's link between organ removal and GI cancers (for appendectomy).
Adequacy of the interpretation (by the archive): not applicable