Colorectal cancer in young adults: a retrospective study of 32 tunisian patients

Young people under the age of 40 with colorectal cancer represent a distinct subgroup with a more aggressive disease behaviour compared to older patients. This study aim to provide an updated overview on clinicopathological features, treatment and outcome of colorectal cancer in young adults under the age of 40. In our retrospective study, we reviewed 32 cases of colorectal cancer in young adults aged less than 40 years that were diagnosed at the pathology department of Mongi Slim hospital over a fifteen-year period (April 2000 - November 2014). Our study group included 13 male and 19 female patients (sex-ratio M/F = 0,68) between 17 and 39 years of age (mean = 31,25 years). The presenting clinical symptoms were dominated by altered bowel habits (n=17), followed by bleeding per rectum (n=16). Histopathological examination of the surgical and biopsy specimens established the diagnosis of mucinous adenocarcinoma in nine cases, well-differentiated adenocarcinoma in 11 cases, moderately differentiated adenocarcinoma in six cases, poorly differentiated adenocarcinoma in four cases and signet ring cell carcinoma in two cases. The tumours were classified after surgery as stage I (n = 2) (6%), stage IIA (n = 7) (22%), stage IIB (n=4) (13%), stage IIC (n=1) (3%), stage IIIB (n=8) (25%), stage IIIC (n= 4) (12%), stage IVA (n=4) (13%) and stage IVB (n=2) (6%). During the follow-up period which ranged between one month and 9 years, local recurrence of the tumour occurred in six cases, seven patients had hepatic metastases and seven patients died after a mean follow-up period of seven months. Molecular genetic studies are increasing the understanding of the pathobiology of colorectal cancer and may ultimately allow at-risk patients to be identified at an earlier stage.


Introduction
Colorectal cancer (CRC) arises predominantly in the older population, with more than 90% occurring after the age of 55 years [1]. Colorectal cancer is infrequent before 40 years of age and is associated with a poor outcome due to advanced stage at diagnosis and poor differentiation. Controversies and debates regarding the characteristics and the prognosis of CRC in the young population still exist. Hence, young patients represent a specific subgroup of patients requiring further survey. The aim of this study was to retrospectively review the presentation and outcomes of 32 young patients under 40 years of age with CRC over the past 15 years. Our results are analyzed in comparison to a review of the literature.

Methods
We undertook a retrospective study of 32 young patients under 40 years of age who were operated on for colorectal cancer at the surgery department of Mongi Slim hospital of Tunis between April 2000 and November 2014. The cases were retrieved from the files of the registry of the surgery department of the same hospital.
Medical records were scrutinized for epidemiologic characteristics, initial manifestations of the disease, methods of diagnosis, laboratory findings, surgical or palliative therapy and overall morbidity and mortality. Diagnosis of colorectal cancer was based upon histopathological findings. All patients underwent imaging evaluation during the preoperative period. All specimens were surgically obtained. Tissues were fixed in 10% phosphate buffered formaldehyde, embedded in paraffin and sections were prepared for routine light microscopy after staining with haematoxylin and eosin.  Biological tests: Preoperative serum carcinoembryonic antigen levels were performed in 12 cases. They were elevated in four cases (> 5ng/ml) and within normal range in eight cases (< 5ng/ml).
Preoperative serum carbohydrate antigen CA 19-9 levels were performed in three cases. They were elevated in one case ( > 37 U/ml) and within normal range in two cases ( < 37 U/ml).

Discussion
The current definition of young CRC patients remains controversial. (n=1) and weight-loss (n=1). In a recent review of the SEER data of 11071 adolescents and young adults, over 72% presented with either regional or metastatic disease. In comparison, 50-58% of the general population presented with regional or metastatic disease [24]. Many authors postulate that a more biologically aggressive tumour occurs in young patients, based on the finding of a higher percentage of poorly differentiated and mucin-producing cancer [8,25]. In one review of the SEER data, mucinous tumours constituted an average of 21% of the lesions found in young patients compared to 10-12% in older adults, while the percentage of tumours found to be poorly differentiated was 27% compared with 15% for adults over 40 years of age [4].
In our study, the mucinous tumours constituted 28% of young CRC and 13% of tumours were found to have poor differentiation.
Previous studies have shown the presence of signet ring carcinoma in 1,7-11,1% of young CRC [4]. In our study, they represented 6% of all CRC. On the other hand, there are recent population-based studies showing that young patients have not a significantly worse survival rate compared with older ones [4,7,26,27]. In a recent review of the SEER data of 11071 adolescents and young adults the disease-specific survival and the overall survival were comparable to those of the general population [24]. On multivariate analysis, disease stage at the time of the diagnosis was the strongest predictor of mortality [24]. After controlling for disease stage, male gender, black race, and higher grade tumours were associated with worse survival [24]. In our series, local recurrence of the tumour occurred in six cases (19%). Seven patients had hepatic metastases (22%) and seven patients (22%) died after a mean follow-up period of 7 months. A genetic basis for tumorigenesis has been implicated in early onset CRC among young patients. Microsatellite instability has been identified in most of the patients with early onset of CRC, suggesting genetic etiology [28].

Conclusion
In summary, this retrospective study from Tunisia provides an What is known about this topic  Colorectal cancer is infrequent before 40 years of age and is associated with a poor outcome due to advanced stage at diagnosis, delayed diagnosis and poor differentiation;  Accurate diagnosis and staging of colorectal cancer is critical for optimal treatment planning and for determining prognosis.

What this study adds
 This is the first retrospective study from Tunisia that provides an overview on clinical symptoms, radiological features, treatment and outcome in 32 young Tunisian patients under 40 years of age with colorectal cancer.

Competing interests
The authors declare no competing interests.