Immunological effects of heated intraperitoneal chemotherapy can be augmented by thymosin α1.

BACKGROUND: Peritoneal metastases of colorectal carcinoma origin (PM-CRC) are treated by cytoreductive surgery and heated intraperitoneal chemotherapy (HIPEC). However, the majority of patients recur, calling for novel treatments. We explored the immunogenic changes induced by HIPEC and the possibility to use thymosin α1 (Tα1) as an immune-stimulatory agent. METHODS: We used an experimental murine model of PM-CRC combined with mitomycin (MMC)-based HIPEC. We determined immune cell infiltration into tumor metastases after HIPEC administration by means of immunohistochemistry, and determined immunogenic cell death signals in tumor cells by real-time polymerase chain reaction. RESULTS: Mice with PM-CRC treated by HIPEC had increased overall survival (OS) compared to sham-treated mice (median OS 22.8 vs 18.9 days, respectively; P < 0.001). HIPEC induced increased infiltration of CD4+, CD8+, CD68 + and CD20 + cells into omental and visceral metastases at a magnitude of 40-100 %. We searched for potential immune signals induced by HIPEC by determining its effects on known immunogenic cell death proteins (heat-shock protein [HSP]-70, HSP-90 and calreticulin). HIPEC significantly increased HSP-90 mRNA expression (2.37 ± 1.5 vs 1-fold change, P < 0.05). The OS of Tα1 treated mice significantly improved compared to HIPEC-treated mice (16.3 ± 0.8 vs 14.1 ± 0.6 days, respectively, P = 0.02) and vs sham (11.8 ± 0.8 days, P = 0.007). CONCLUSIONS: HIPEC induced immunogenic changes that led to increased immune cell infiltration. These changes were further augmented by Tα1 treatment. Future studies aimed at optimizing Tα1 treatment should focus upon the immune response it evokes.

Vitamin D Deficiency in Patients with Morbid Obesity before and after Metabolic Bariatric Surgery.

BACKGROUND: Metabolic bariatric surgery (MBS) is the most effective treatment for severe obesity. Vitamin D deficiency is a common complication encountered both during preoperative workup and follow-up. AIM: To estimate the prevalence of vitamin D deficiency in patients undergoing MBS. METHODS: Prospectively maintained database of our university MBS center was searched to assess the rate of preoperative and postoperative vitamin D deficiency or insufficiency in patients undergoing MBS over a one-year period. RESULTS: In total, 184 patients were included, 85 cases of Sleeve Gastrectomy (SG), 99 Gastric Bypass (GB; 91 One Anastomosis and 8 Roux-en-Y). Preoperative vitamin D deficiency and insufficiency were respectively found in 61% and 29% of patients, with no significant difference between SG and GB. After six months, 15% of patients had vitamin D deficiency, and 34% had vitamin D insufficiency. There was no significant difference in the rate of vitamin D deficiency or insufficiency and the percentage of total weight loss (%TWL) at 1, 3, and 6 postoperative months between SG and GB. CONCLUSIONS: Preoperative vitamin D deficiency or insufficiency is common in MBS candidates. Regular follow-up with correct supplementation is recommended when undergoing MBS. Early postoperative values of vitamin D were comparable between SG and OAGB.

Cytoreduction surgery with hyperthermic intraperitoneal chemotherapy in recurrent ovarian cancer improves progression-free survival, especially in BRCA-positive patients- a case-control study.

BACKGROUND: Approximately 70% of women diagnosed with advanced-stage ovarian cancer experience disease recurrence. Survival data were compared between a group of recurrent epithelial ovarian cancer (rEOC) patients treated by cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) and a matched group of rEOC patients treated by systemic chemotherapy only (without surgery). Treatment outcome in relation to the patients' BRCA status was compared. METHODS: Twenty-seven rEOC patients treated by cytoreduction and HIPEC were selected from our database and matched (1:3) with 84 rEOC patients treated with chemotherapy only. Progression-free survival (PFS) and overall survival (OS) in the two groups were analyzed and compared. RESULTS: The estimated median PFS was 15 months in the HIPEC group and 6 months in the systemic chemotherapy group (P = 0.001). The median OS following HIPEC treatment has not been reached, since more than 70% of the women were alive at the time of analysis. The 5-year survival rate was significantly higher in the HIPEC treated patients compared to that of the controls (79% vs. 45%, P = 0.016). BRCA status did not affect PFS. CONCLUSIONS: HIPEC after surgical cytoreduction in patients with rEOC appears beneficial compared to systemic chemotherapy treatment alone. The benefit is even greater in BRCA mutation carriers.