Mneimneh, Wadad

101 Background: Exosomes mediate intercellular communications and have pivotal roles in cancer development. CD63 and CD9 are widely accepted exosomal markers. The effect of concurrent chemoradiation on the expression of exosomal markers is unknown. Here we explored the effect of neoadjuvant concurrent chemoradiation (NCCR) on exosomal markers (CD63 and CD9) expression in patients with locally advanced rectal cancer (LARC). Methods: Between 2015 and 2018, 33 patients had LARC treated with NCCR and had pre NCCR biopsy and post NCCR resected rectum examined for exosomal markers expression using immunohistochemistry. Two pathologists independently scored CD63 and CD9 staining in the tumor. Staining intensity was graded from 1-3. Staining percentage was estimated in 10% increments. Mean quick-score (Q-score) was calculated (intensity x percentage). Un-Paired t test was used for statistical analysis. Results: In our cohort, median age was 59 years. Males represented 79% of the patients. Caucasians, African American and other ethnic groups represented 70%, 27% and 3% respectively.The mean tumor CD63 score in pre NCCR biopsy vs post NCCR resected rectum was 106 vs 165 (p = 0.0022). The mean tumor CD9 score in pre NCCR biopsy vs post NCCR resected rectum was 136 vs 215 (p < 0.0001). The exosomal markers expression in the adjacent normal mucosa (ANM) from pre NCCR biopsy and post NCCR resected rectum was only performed in16 out of 33 patients (due to ANM tissue availability). The mean ANM CD63 score in pre NCCR biopsy vs post NCCR resected rectum was 166 vs 183 (p = 0.37). The mean ANM CD9 score in pre NCCR biopsy vs post NCCR resected rectum was 104 vs 145 (p = 0.0897). Conclusions: In patients with LARC, the expression of exosomal markers (CD63 and CD9) increased after treatment with NCCR. Our results show that the expression of CD63 and CD9 is relatively higher in rectal cancer specimens treated with NCCR and thus suggest a possible role of these exosomes in adaptive response to NCCR. Further follow-up and laboratory studies are required to precisely understand the underlying mechanism(s).

Only 50% to 70% of patients with mesothelioma report asbestos exposure. Other exposures (eg, radiation) play a role in some cases, but some patients have no obvious cause. We describe a series of patients with long-standing indwelling intra-abdominal shunt catheters who developed malignant peritoneal mesothelioma, suggesting a novel association. We identified 7 patients who had shunts and subsequently developed mesothelioma (5 women; median age: 31 y, range: 18 to 45 y). Clinical history and pathology materials were reviewed, and RNA sequencing was performed. Clinical presentations varied; 6 patients had hydrocephalus and a ventriculoperitoneal shunt, and 1 patient had portal hypertension and a portoatrial shunt. The median duration of shunt therapy in 5 cases was 29 years (range: 12 to 35 y); the remaining 2 patients also had shunts for many years, but specific details were unavailable. Two patients had radiotherapy for malignancies in childhood. One had an alleged exposure to asbestos and 1 had prior exposure to talc. The rest had no known risk factors. Histologically, all tumors were purely epithelioid. Treatments included surgical debulking, chemotherapy, and palliative care. All 7 died of disease (median survival: 7 mo, range: 1 to 18 mo). Molecular testing showed loss of NF2 and CDKN2A/B and a BAP1 mutation in 1 case, and no genomic alterations associated with mesothelioma in 2 cases. Peritoneal mesothelioma may represent a complication of long-standing indwelling shunt catheters. The mechanism is unknown, but chronic peritoneal irritation may play a role. Albeit rare, mesothelioma should be considered in patients with a shunt who present with new ascites.