Cancer of the Appendix on the Rise in Younger Patients With Appendicitis

Lorraine L. Janeczko, MPH

March 29, 2022

Younger patients with appendicitis appear to be increasingly likely to have cancer of the appendix, a new study suggests.

While acute appendicitis can often be managed with antibiotics instead of surgery, patients who do not have surgery need to be closely followed to avoid missed diagnoses, the authors write.

Dr Mustafa Raoof

"The most important finding is that between 2004 and 2017, relative to right-sided colon cancer, the number of appendiceal cancer cases increased," said Mustafa Raoof, MD, who was not involved in the study. He is a surgical oncologist and an assistant professor of surgical oncology at City of Hope Comprehensive Cancer Center in Duarte, California. "Approximately one fourth of these were carcinoid tumors, and this category saw the greatest increase, particularly in individuals under 50 years of age.

"There is a push to treat acute appendicitis with only antibiotics to avoid surgery," Raoof told Medscape Medical News by email. "One underappreciated downside of this strategy is that an appendiceal cancer can be missed if the appendix is not removed."

As reported in Journal of the American College of Surgeons, lead study author Michelle C. Salazar, MD, MHS, a general surgery resident at Yale School of Medicine in New Haven, Connecticut, and her colleagues conducted a retrospective analysis of the National Cancer Database (NCDB). The NCDB contains hospital registry data of around 70% of new cancer diagnoses in the United States.

The researchers extracted data on patients aged 18 years and older who were diagnosed with right-sided colon cancer between 2004 and 2017 and who underwent appendectomy. The authors also identified all patients with appendiceal cancer. They divided that group into patients with carcinoid tumors and those with other types of appendiceal cancer. They also investigated trends by age group.

  • Of 387,867 patients with right-sided colon cancer, 19,570 (5%) had appendiceal cancer, and 5628 of those patients (29%) had carcinoid tumor. The odds of appendiceal cancer, compared to other right-sided colon cancers, rose over the years studied (odds ratio [OR], 2.56; 95% CI, 2.35 – 2.79).

  • This increase in odds occurred in all age groups but was steepest among patients between 40 and 49 years of age, among whom it increased from 10% in 2004 (95% CI, 9 – 12) to 18% in 2017 (95% CI, 16 – 20; P < .001).

  • Odds of appendiceal carcinoid, compared to other appendiceal cancers, also rose during this period (OR, 1.70; 95% CI, 1.40 – 2.07). The sharpest increase occurred in the likelihood of carcinoid in patients younger than 40, from 24% in 2004 (95% CI, 15 - 34) to 45% in 2017 (95% CI, 37 – 53; P < .001).

"The findings in this study are yet another reason to temper excitement about nonoperative management of acute appendicitis in adults," Richard S. Hoehn, MD, a surgical oncologist at University Hospitals Seidman Cancer Center in Cleveland, Ohio, said. "The study is important because it reveals a potential risk of deferring appendectomy in adult patients with appendiceal pathology.

Dr Richard Hoehn

"As our pathologic examinations of appendiceal cancers improve, we are gaining better understanding of these tumors and how to best manage these patients," Hoehn, who also was not involved in the study, added in an email. "The findings should make surgeons more suspicious of malignant causes of acute appendicitis in adults, especially those under 40. Colonoscopy and appendectomy are necessary in adult patients with appendicitis."

Gregory Botta, MD, PhD, a medical oncologist and associate professor of medicine at the University of California San Diego Health, mentioned limitations of the study in an email. They include the NCDB's omission of around 30% of cases nationally and the study's omission of patients diagnosed with primary appendiceal tumor, as well as patients who underwent total colectomies and those who did not have surgery.

"Appendiceal tumors are not normally seen during colonoscopies; screening colonoscopies are not recommended to younger patients under 40, and there is less surgical management for appendicitis," explained Botta, who also was not involved in the study. "Thus, the cause of the increasing incidence is not due to increased detection on surveillance.

"Gastrointestinal oncologists are seeing an increase in colon cancer in younger patients and a parallel increase in appendix tumors. While carcinoid tumors are usually found localized and [are] therefore curable postsurgical resection, adenocarcinoma or mucinous subtypes tend to be more diffuse, metastatic, and noncurable," he added. "Although the increase in colon cancer is being found in our younger population, the authors hint at causes not captured by the NCDB, including environmental exposures or each patient's diet."

"There is no good answer as to why there is an increase in carcinoids," Salazar said in a press release. "It could be due to environmental reasons, or it could be due to better diagnostics technology."

The researchers and independent experts share concerns that, because surgery provides the only definitive diagnosis of appendiceal cancer, among patients managed nonsurgically, there may be a delay in cancer diagnosis.

"I would counsel patients based on age," Salazar added. "If you're older, you are at less risk for appendiceal cancer and greater risk for complications from surgery. Younger, healthy patients are more likely to be able to tolerate an operation and may want to rule out cancer by undergoing the operation. The characteristics of appendicitis should be considered in the decision."

Funding information was not provided. The authors, Raoof, Hoehn, and Botta have disclsoed no relevant financial relationships.

J Am Coll Surg. Published online March 17, 2022. Abstract

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