In present study, we performed a retrospective analysis of clinicopathological features of 50 patients with appendiceal mucinous adenocarcinoma to investigate the possible prognosis related factors. Our results indicated that cytoreduction for appendiceal mucinous adenocarcinoma was conducted on 50 patients (24 males and 26 females), with a median age of 52.5 years at the time of surgery (range 31-71 years).
Immediate progression was considered in the majority of patients who underwent debulking surgery (CCR2/3). Only 20 patients had CCR0/1 cytoreduction. So, progression-free survival was not discussed in this study. The median overall survival (OS) time was 24 months, while the 2-, 3- and 5-year survival rates of 53%, 24% and 8%, respectively. At the last follow-up in December 2018, 13 patients were still alive. Multivariate analysis revealed that patients who had less than 50% Ki-67 expression and CCR0/1/2 score had significantly better OS rate than their respective counterparts.
Despite better prognosis was observed in patients with well-differentiated adenocarcinomas of the appendix than those with poorly differentiated adenocarcinomas and the AJCC TNM system defined histological grade was considered as a critical prediction index for the prognosis in patients with appendiceal adenocarcinoma, distinctly different Cancer-specific survival was found in Stage IV (according toAJCC Staging Manual 7th edition) patients with moderately and poorly differentiated mucinous adenocarcinomas were found, which against the combination of these 2 histological grades according to recent publication . In a previous study by Xie et al, they provided a better and more accurate prognosis prediction model in patients with appendiceal adenocarcinoma based on the data obtained from SEER database. More importantly, they also suggested that the depth of adenocarcinoma invasion may be employed as a predict index for surgical approach optimization. Regarding to the unique biological behavior of mucinous adenocarcinomas of the appendix, intraoperative HIPEC is recommended by their study. However, they did not confirm if it is necessary to perform systematic chemotherapy in patients with adenocarcinoma of the appendix.
Mucinous adenocarcinomas are considered as the unique appendix tumours based on their particular biological behavior. Among different types of appendiceal neoplasms, greater potential of the presence of serosa invasion and peritoneum or abdominal cavity spreading and followed by PMP formation was found in the mucinous adenocarcinomas. As a rare clinical disease, the characteristics of PMP include excessive accumulation of gel-like mucinous peritoneal fluid in the peritoneal or pelvic cavity, thereby resulting in clinical manifestation such as abdominal pain, abdominal mass, progressive increasing of the abdominal circumference and severe weight loss [13, 14]. Variable results were found on the survival rate of patients with mucinous appendiceal adenocarcinoma according to previous reports[15-17]. Overman et al. found that stage IV diseases were more likely to be presented as mucinous adenocarcinomas than those with non-mucinous adenocarcinomas . Therefore, the subdivision of the patients into Stage I-III and IV was conducted by Xie et al, and their results showed that significantly decreased 5-year overall survival was found in patients with mucinous adenocarcinoma, which indicated the different biological behaviors between mucinous and non-mucinous adenocarcinomas.
Multidisciplinary therapies employing surgical resection followed by adjuvant chemoradiation treatment, have been increasingly performed as the treatment modality in patients with resectable digestive tract cancers [18, 19]. However, controversy was remained existed about whether the multidisciplinary therapies could result in a survival improve effects in patients with adenocarcinoma of the appendix. Since the development of PMP was the frequently presented complications in patients with mucinous adenocarcinomas of the appendix could, cytoreductive surgery and HIPEC have been suggested as first-line therapies . Recently, Asare et al demonstrated that systematic chemotherapy could lead to a significantly improved OS without considering the history feature of the adenocarcinoma (HR:0.79; 95% CI:0.69-0.90; P = 0.0005 and HR:0.84; 95% CI: 0.75-0.95; P = 0.004 for mucinous and nonmucinous, respectively). Moreover, systemic chemotherapy seems to have no effects on the patients with mucinous and well-differentiated adenocarcinomas . In our study, multivariate analysis revealed that patients with CCR0/1/2 score had significantly improved 5-year overall survival rate than those with CCR3, whereas The OS times for the cohort based on CCR score of tumors were 28 months and 12 months, respectively, for CCR0/1/2, and CCR3. These results also supported the effectiveness of HIPEC in the treatment of mucinous appendicular adenocarcinoma
There are also some limitations in our study. Firstly, this is a single center small size study and insufficient sample size could affect the final conclusion. Secondly, the diagnosis value of Ki-67 expression was also implicated by the results obtained here, and although we calculated accurate cut-off value of Ki-67 level by ROC curve, lacking of comparison results with golden standard could result in failure to elucidate the diagnostic efficacy of Ki-67. Third, the detailed mechanisms that resulted in the efficacy of CRS should be elucidated for identification of the exact role of CRS in mucinous appendicular adenocarcinoma. Taken together, further investigation is still important to identify the biomarker role of CCR scores by a multicenter clinical large sample size study with prognosis results.