Background The role of systemic chemotherapy (SC) in conjunction with cytoreductive surgery (CS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in appendiceal mucinous carcinoma peritonei (MCP) is unknown. Methods A retrospective review (1999–2011) of MCP patients who had undergone CS/HIPEC with or without perioperative SC. Results Twenty-two low-grade MCP patients treated with CS/HIPEC and SC were matched to patients who received CS/HIPEC alone. Median overall survival (OS) was 107 months for patients treated with perioperative SC compared to 72 without (P = 0.46). CS/HIPEC was performed on 109 patients with high-grade MCP: 70 were treated with perioperative SC, while 39 were not. Median OS (22.1 vs. 19.6 months, P = 0.74) and progression-free survival (PFS) (10.9 vs. 7.0 months, P = 0.47) were similar in patients treated with SC compared to CS/HIPEC alone. Progression while on pre-operative SC was seen in eight patients (17%), while four (8%) had a partial response. Treatment with postoperative SC was associated with longer PFS (13.6 months) compared to pre-operative SC (6.8 months, P < 0.01) and CS/HIPEC alone (7.0 months, P = 0.03). Conclusions Post-operative SC appears to improve PFS in patients with high-grade appendiceal MCP treated with CS/HIPEC. In contrast, there is no evidence to support the routine use of perioperative SC in low-grade disease.

Over 30% of primary prostate cancers contain a consensus deletion of an approximately 800 kb locus on chromosome 6q15.1. The MAP3K7 gene, which encodes TGF-β Activated Kinase-1 (Tak1), is a putative prostate tumor suppressor gene within this region whose precise function remains obscure. In this study, we investigated the role of Tak1 in human and murine prostate cancers. In 50 well-characterized human cancer specimens, we found that Tak1 expression was progressively lost with increasing Gleason grade, both within each cancer and across all cancers. In murine prostate stem cells and Tak1-deficient prostatic epithelial cells, Tak1 loss increased proliferation, migration, and invasion. When prostate stem cells attenuated for Tak1 were engrafted with fetal urogenital mesenchyme, the histopathology of the grafts reflected the natural history of prostate cancer leading from prostatic intraepithelial neoplasia to invasive carcinoma. In the grafts containing Tak1-suppressed prostate stem cells, p38 and JNK activity was attenuated and proliferation was increased. Together, our findings functionally validate the proposed tumor suppressor role of Tak1 in prostate cancer.