Colorectal cancer (CRC) is one of the most common malignancies in the world, and responsible for a huge amount of cancer-related deaths. There are many factors linked to CRC development, namely: age, male gender, smoking, diabetes, drinking alcohol, genetic diseases, chronic inflammatory bowel disease (IBD), low-fiber diet... Some of them can be manipulated, others cannot. Human gut microbiota plays an important role in host's immunity, in gut and systemic diseases. Inflammation may interact with gut microbiota and cancer development. In this setting, ileocecal appendix appears to be a "safe house for biofilm formation to preserve and protect commensal bacteria". Studies suggested that large bowel microbiota can be changed after appendix removal. It is well known that appendectomy is linked to an increased risk of Crohn's disease and ulcerative colitis. Following these data, how about colorectal cancer development after appendectomy? Can microbiota's changes after appendectomy be a risk for CRC development?
Shih-Chi Wu et al. from Taiwan compared the CRC development between a study group of 75979 patients submitted to appendectomy between 1997-1999, with a comparison cohort of 303640 patients who did not had an appendectomy. Both groups were similiar. Were excluded from both groups patients with cancer history, with IBD, and with a cancer diagnosis within the 18 months following appendectomy.
Data analysis revealed an increased risk of CRC development in appendectomy group after a follow-up period of 14 years (0,04 % higher). Figure. The authors concluded that the incidence of CRC in patients submitted to appendectomy due to appendicitis and incidental appendectomy was 1,02 and 2,90 fold higher than in the comparison group, respectively. Interestingly, is the fact that CRC appears much earlier in the appendectomy group during follow-up, comparing to the control group. Another important data is the decreasing incidence of CRC in the appendectomy group throughout the follow-up years, while in the comparison group this trend is not present. Additionally, comparing subgroups of patients with >60 years and <60 years between both cohorts, the increased risk of cancer after appendectomy was most evident in the >60 years subgroup.
"In this retrospective cohort study with a 14-year follow-up, we found that patients who underwent an appendectomy had a 1,14 fold higher risk of colorectal cancer than the general population."
Shih-Chi Wu et al.
Large bowel microbiota plays an important role in colitis-associated cancer. Also, in another study appendicitis was considered the first manifestation of CRC, confirming the relation between the appendix and colon cancer. However, an according to Shih-Chi Wu et al. the pathophysiology of cancer development associated with appendicitis may be different than the mechanism responsible for cancer development following appendectomy. The authors point out a dysbiosis caused by the impaired production of biofilm after appendectomy responsible for tissue inflammation, ultimately leading to CRC development. The previous abundant biofilm in the appendix, cecum and right colon, may justify the findings of lower incidence of cancer in these sites in both cohorts (lesser degree of dysbiosis due to greater biofilm protective effect than in the rectum).
Why does the cancer incidence decreases to the general population level throughout follow-up years? The explanation seems evident but studies are needed. The microbiota changes following appendectomy may probably last for a short period of time, not having a long-term effect in carcinogenesis.
"The risk decreases to the level of the general population 6,5 years later."
Shih-Chi Wu et al.
Since comorbidities were similiar in both the appendectomy and comparison cohorts, the authors state that the fact that the older patients subgroup had a higher risk of cancer following appendectomy cannot be attributed to age-related factors, but to microbiota changes. Is there an age-difference in the relationship between appendectomy/appendicits and cancer? Studies are lacking, I think.
Lastly, two points are worth to mention:
The increased risk of CRC development after incidental appendectomy. Do not forget that patients with cancer diagnosis within the 18 months following appendectomy were excluded, which means there was not probably a cancer at appendectomy time. Will this have legal implications in the future?
Typical pathophysiology of CRC takes about 10 years. In this study cancer incidence was higher in the 1,5 and 3,5 years of follow-up. Does appendectomy accelerates carcinogenesis? Will appendectomy implicate a colon surveillance in the following years?
The authors conclude that "overall risk elevation is estimated for 14%, but much greater for the elderly patients". This study may advise the need of clinical and colon surveillance (endoscopic) for patients submitted to appendectomy. Ultimately (and for the fanatics), this may be one more reason to the reborn idea of conservative treatment of appendicitis. As for myself, I will keep treating appendicitis with surgery.
Link to PubMed:
by Dr. Carlos Eduardo Costa Almeida
General Surgeon