Chronic inflammation-induced carcinogenesis is a commonly accepted mechanism for several malignancies [3]. In colon cancer, systemic inflammation not only affects cytokines, but also promotes angiogenesis and metastasis formation [12]. Therefore, several systemic inflammatory-associated markers, such as C-reactive protein, lymphocyte-to-monocyte ratio, platelet-to-lymphocyte ratio, and NLR, have been used as outcome predictors [4-7].
Tumor-associated cytokines and growth factors enter the circulation causing a systemic response. These factors, which cause tumor angiogenesis and possibly neoplasm progression, may lead to an increase in neutrophil count [13]. Alternatively, the absolute lymphocyte count is considered to reflect the immune response of patients with cancer; lymphopenia is also correlated with worse outcomes in patients with colorectal cancer [14]. Therefore, the NLR can be considered a parameter that reflects the relationship between pro-tumor inflammatory and antitumor immune factors.
Multiple studies have focused on the association between the preoperative NLR and colon cancer outcomes. A normal NLR is considered to range between 0.78 and 3.53 [15]. A high NLR (>5) has been identified as a prognostic factor for poor OS and early recurrence [9, 10, 16]; however, in our study, patients with perforated colon cancer and a high NLR showed no significant differences in OS (p=0.637) and DFS (p=0.827).
A high NLR has also been associated with a higher T and N stage and a higher incidence of extramural venous invasion [17]; however, in our study, T and N staging was not associated with a high NLR. In patients with perforated colon cancer, regardless of whether they are showing clinical signs of peritonitis, perforation-related infection or inflammation is difficult to detect. Therefore, in these patients, the elevated neutrophil level associated with infection may be higher than the normal preoperative NLR. Consequently, the preoperative NLR may not reflect the balance between cancer-related inflammation and the immune response in patients with perforated colon cancer.
We reexamined the 12 enrolled patients with pT3 perforated colon cancer and classified them according to the cause of perforation. Among them, six had recorded perforation with abscess formation, four had proximal perforation (perforation site proximal to the primary tumor: 3.5, 2.3, and 3.7 cm; one patient had cecal perforation and ischemic change), and two had walled-off abscess with adhesion to the lateral abdominal sidewall.
Approximately 1% of colon cancer patients have perforation at the proximal site of the cancer [18]. These patients may have obstructive signs and a higher operative mortality rate than those with obstruction only.
Although abscess formation is rare, occurring in approximately 0.3 to 4% of colon cancer patients, it represents the second most common presentation of perforated lesions [19]. The pathological definition of an abscess is a localized collection of neutrophils near the tumor in the resected specimen. However, when it comes to T stage, this can vary according to the version of the American Joint Committee on Cancer (AJCC) guidelines and the pathologist’s opinion. For example, if a specimen showed perforation of the tumor in which the tumor cells are continuous with the serosal surface through inflammation, then the patient would have pT4a disease according to the AJCC 8th edition. However, according to the AJCC 7th edition, the patient would have pT3 disease, because of a lack of tumor cells on the serosa[20, 21]. In this study, patients were enrolled since 1995. Some patients with perforated colon cancer and abscess formation would have been diagnosed with pT3 disease according to the AJCC 7th or previous editions; however, today our pathologists would be more likely to impress these patients with pT4a disease according to the latest version of the AJCC guidelines.
Walled-off abscess formation is more likely to be clinically or surgically diagnosed, usually with localized abscess formation and adhesion to adjacent organs. Our pathologists also classified these as perforation. According to a literature review [22], there was no statistically significant difference in prognosis between patients with walled-off abscess formation and those with free perforation.
This study has several limitations. First, this was a single-center retrospective study involving a small number of patients. Second, preoperative data were collected using the latest data point before surgery, either in the emergency room or during admission, if elective surgery was performed. Third, the definition of perforation was based on pathology reports. Some patients who may have initially presented with local abscess formation and no peritoneal signs could have been enrolled in our study and undergone further elective surgery, rather than emergent surgery. Therefore, the results may not reflect equivalent clinical conditions among patients. Further larger studies are required to validate our findings.