Surgery for Appendicitis Tied to Sharply Lower Later Colorectal Cancer Risk Than Antibiotics Alone

Patients who had their appendix surgically removed during an episode of acute appendicitis were substantially less likely to be diagnosed with colorectal cancer in later years than comparable patients whose appendicitis was treated with antibiotics alone, according to new research scheduled for presentation at the American College of Surgeons Clinical Congress 2026 in Washington. In the large matched cohort study, which drew on records from more than 30,000 patients across 168 health care organizations, colorectal cancer was subsequently diagnosed in 0.7 percent of those who underwent an appendectomy, compared with 1.7 percent of those managed without surgery, a relative risk reduction of 58 percent.

The findings arrive at a moment when the standard management of appendicitis is actively shifting. Over the past decade, antibiotic therapy has become an accepted alternative to the operating room for select patients, driven by trials showing that many uncomplicated cases resolve without surgery. That shift has largely been evaluated on short-term outcomes such as recurrence, complications, and quality of life. The new analysis raises a different question: whether leaving the appendix in place after an inflammatory episode carries long-term oncologic consequences that have so far gone unexamined.

Senior author Valentine Nfonsam, MD, MS, FACS, FASCRS, professor and executive vice chair of the department of surgery at Morehouse School of Medicine, said the motivation for the study grew out of that gap in the evidence. Antibiotic management remains an important option, he emphasized, but the discussion around nonoperative treatment has focused almost entirely on the immediate episode of appendicitis rather than on what may follow years later. The research team wanted to know whether the choice made in the emergency setting could shape cancer risk over the long arc of a patient’s life.

To answer that question, the investigators performed a retrospective cohort study using the TriNetX Global Collaborative Network, a federated database aggregating electronic health records from 168 health care organizations. They identified patients diagnosed with acute appendicitis who were treated either with an appendectomy or with antibiotics alone. After matching the two groups by baseline characteristics to reduce confounding, each treatment arm initially included 15,774 patients. Once the researchers excluded individuals who had received a colorectal cancer diagnosis before the study’s outcome period, the final cohorts comprised 15,616 appendectomy patients and 15,295 patients treated with antibiotics.

The numbers that emerged were striking. Colorectal cancer was diagnosed in 110 patients who had undergone appendectomy, or 0.7 percent of that group, compared with 254 patients treated with antibiotics alone, or 1.7 percent. After accounting for the matched design, the surgical group carried a 58 percent lower relative risk of a subsequent colorectal cancer diagnosis. Because the study is observational, it establishes an association rather than proof of causation, and the authors are careful about what the data can and cannot show. Still, the magnitude of the difference in a cohort of this size is difficult to dismiss as statistical noise.

Several biological explanations could account for the pattern, and the researchers outline them as hypotheses rather than conclusions. One possibility is detection bias in a favorable sense: an appendectomy gives surgeons a specimen for pathologic examination, and findings from that analysis can prompt additional diagnostic testing that might otherwise be delayed. In some patients, appendicitis may in fact be an early manifestation of an undiagnosed colorectal cancer rather than a precursor to one. An occult tumor on the right side of the colon, for example, can obstruct drainage from the appendix and first present as acute appendicitis, meaning the surgery may simply be unmasking disease that already exists.

A second line of explanation concerns the appendix itself, an organ long dismissed as a vestigial leftover of evolution. Emerging research suggests it plays an active role in the intestinal immune system and the gut microbiome, the community of bacteria and other microorganisms inhabiting the digestive tract. According to Nfonsam, the appendix contains a substantial amount of lymphoid tissue thought to contribute to immune functioning. Because alterations in inflammation and in the microbial environment have been linked to processes involved in colorectal cancer, the appendix’s biological functions represent a plausible area for further investigation. Removing the organ also eliminates a potential ongoing source of inflammation at the junction of the small and large intestines.

Nfonsam cautioned that the study cannot settle the mechanistic question. The appendix is rich in lymphoid tissue and participates in the local microbiome and immune system, he noted, and whether persistent inflammation or shifts in the microbial environment contribute to cancer development is biologically plausible, but the retrospective design cannot answer it directly. Distinguishing between the detection effect, the removal of an inflamed organ, and any true protective biology will require prospective work with longer follow-up and more granular clinical data.

The practical message from the researchers is not that every patient with appendicitis should undergo surgery to prevent cancer. Antibiotic management remains a legitimate and widely used option, and the absolute difference in cancer diagnoses, while meaningful, involves a small fraction of patients in both groups. Instead, the authors argue that treatment should not be one size fits all. Age, genetic predisposition, family history, and other established colorectal cancer risk factors may ultimately help clinicians select patients for nonoperative management and plan appropriate surveillance for those who choose it.

The research will be presented at the American College of Surgeons Clinical Congress 2026, held in Washington from September 26 to 29, where thousands of surgeons convene to advance surgical quality, patient safety, and access to care. The abstract was reviewed and selected by the congress program committee but has not yet undergone full peer review, a limitation the authors and the college both acknowledge. Co-authors on the work include Meghana Akula, Syed Fahad Gillani, Miriannie Rivera Valerio, Ahmad Zeineddin, Cassie Bowers, Miriam Michael, Quyen D. Chu, Christine E. Nembhard, and May C. Tee, and the authors report no disclosures. If the association holds up under peer review and prospective study, it could reshape how surgeons and patients weigh the long-term stakes of a decision that has, until now, been framed almost entirely in terms of the short-term recovery.

Subject of Research: Long-term colorectal cancer risk after appendectomy versus antibiotic treatment for acute appendicitis

Article Title: Appendectomy for appendicitis associated with 58% lower colorectal cancer risk than antibiotics alone

Article References: Appendectomy for appendicitis associated with 58% lower colorectal cancer risk than antibiotics alone. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: appendectomy, appendicitis, colorectal cancer, antibiotics, American College of Surgeons, gut microbiome, inflammation, cancer risk, retrospective cohort study, surgery, TriNetX, oncology