Management and prognostic prediction of appendiceal mucinous adenocarcinoma with peritoneal metastasis: a single center study in China

The study was approved by the Ethic committee of Aerospace Central Hospital, Beijing, China (no.20161109-ST-07). Written inform consent was obtained from all the included patients, and all the participants have given the consent for their images.

A retrospective analyses of a cohort of appendiceal mucinous adenocarcinoma patients with peritoneal metastasis from January, 2013 to December, 2017 in the Department of Myxoma of Aerospace Central Hospital, Beijing, China. All the patients were screened from high grade peritoneal pseudomyxoma and confirmed by 2 experienced pathologists. Mucinous adenocarcinoma was featured by invasive peritoneal lesions comprised with abundant glandular or signet ring cell morphology epithelium with sufficient architectural complexity and cytological atypia to a diagnosis confirmation of mucinous carcinoma. The diagnosis criteria were according to the 8th Edition of American Joint Committee on Cancer [7]. The exclusion criteria were as follows: 1. Lost follow-up; 2 combined with other severe organic disease; 3. with incomplete disease history. Finally, a total of 50 patients were included for analyses.

Sugarbaker technique of cytoreductive surgery (CRS)/ hyperthermic intraperitoneal chemotherapy (HIPEC) described previously were employed here [8]. Briefly, aggressive cytoreduction was employed to remove as much macroscopic disease as possible. HIPEC is administered at thecompletion of cytoreduction using closed technique. Two inflow and two outflow catheters were allocated in the abdomen. After temporary the abdominal skin closure, mitomycin at the dosage of 20 mg/m² was performed to increase to an inflow temperature of 41 to 42 °C and follow by a 60 min’ peritoneal cavity circulation (Fig. 1).

The interested variables included age of the patient at the time of diagnosis, sex, Prior surgical score (PSS), with/without preoperative intravenous chemotherapy, preoperative intraperitoneal chemotherapy, hemoglobin levels, albumin levels at the time of admission, preoperative CEA/CA125/CA199 elevation, Intraoperative peritoneal cancer index (PCI), completeness of cytoreduction (CCR) score, intraoperative HIPEC; pathological data include: with/without lymph node metastasis, presence or absence of signet ring cells. Among these characteristics, PSS was scored 0–3, and PSS-0: biopsy only, PSS-1: minimal prior dissection with only one dissected abdominal region; PSS-2: 2–5 regions dissected and PSS-3: extensive prior cytoreduction (more than 5 regions). PCI stands for a clinical integration of both peritoneal implant size and distribution of peritoneal surface malignancy [9]. For PCI evaluation, 13 anatomical regions were divide based on the region of the abdomen and pelvis. The largest size malignant nodule at each region was scored and the lesion size score from the all 13 regions was summated as the PCI for the individual patient [8]. CCR score was recorded at the time of the completion of the surgical procedure. CCR-0: no peritoneal seeding was visible after the cytoreduction, CCR-1: residual tumour nodules less than 2.5 mm, CCR-2: residual tumour nodules 2.5 mm to 2.5 cm and a CCR-3: larger than 2.5 cm persistent tumor nodules [10].

Statistical analyses were employed using SPSS 20.0(SPSS Inc. Chicago, IL). Continuous data were expressed as medians and range. Categorical variables were presented as number and percentages. The associations between the clinicopathological variables and survival data was identified by univariate and multivariate Cox proportional hazard regression models. All variables with p value < 0.3 in the univariate analysis were further analyzed with in the multivariate Cox model. Survival data calculation and comparison were respectively performed with the Kaplan-Meier method and the log-rank test. Statistically significance was considered when the presence of two tailed P values < 0.05.

Cytoreductive surgery for appendiceal mucinous adenocarcinoma was carried out on 50 patients (26 males and 24 females), with a median age of 52.5 years at the time of surgery (range 31–71 years). The median survival rate was 24 months, whereas 2-,3- and 5-year survival rates of 53, 24 and 8%, respectively. Prior systemic chemotherapy was performed in 13(26%) patients, whereas 15(30%) patients were treated with HIPEC. Forty-eight (96%) patients were with bloating or ascites or abdominal mass manifestation. Comorbidities including ileus, anemia and hypoalbuminemia were respectively found in 18(36%), 23(46%) and 9(18%) patients. Increased levels of Serum tumor maker CEA, CA125 and CA199 were respectively in 33(66%), 34(68%) and 27(54%) patients. The number of patients with PCI score > 26, 13–26, and < 13 were respectively 34(68%), 14(28%) and 2(4%). Demographic and pathological characteristics of patients were listed in Table 1.

According to the multivariate analysis, significantly better overall survival rate was found in the patients with a low Ki-67 expression (less than 50%) and CCR0/1/2 score than their corresponding counterparts (Table 2).

At the last follow-up in December 2018, 13 patients were still alive. The median overall survival (OS) time was 24 months, while the 2-, 3- and 5-year survival rates of 53, 24 and 8%, respectively. The 1-year, 2-year survival rates for CCR0/1/2 and CCR3 were 90% vs 28, 66% vs 0%, respectively. The 1-year, 2-year survival rates for Ki-67<50% and Ki-67 ≥ 50% were 67% vs 50, 39% vs 0%, respectively (Fig. 2).