Thymosin alpha 1 as an adjuvant to hyperthermic intraperitoneal chemotherapy in an experimental model of peritoneal metastases from colonic carcinoma.

INTRODUCTION: Heated intraperitoneal chemotherapy (HIPEC) is currently implemented in the treatment of peritoneal metastases from colorectal carcinoma (PM-CRC) origin. However, recurrence is common and the effectiveness of HIPEC has been questioned. The aim of this study was to evaluate the use of thymosin alpha 1 (Tα1), an immunomodulatory molecule, as an adjuvant to HIPEC treatment. METHODS: We developed an experimental model of HIPEC by the induction of PM-CRC in C57BL mice and intra-abdominal perfusion of mitomycin C (MMC). Mice were treated with Tα1 at 0.6 mg/kg for 5 days after HIPEC. Clinical and immunological parameters were compared between HIPEC and HIPEC + Tα1 groups. RESULTS: Treatment with Tα1 increased overall survival of mice compared to HIPEC treatment alone and sham-treated animals (16.1 ± 0.8 vs. 14.1 ± 0.6 and 11.8 ± 0.8, respectively, p = 0.02). Tα1 had no direct anti-tumor effect, as seen by lack of inhibition of tumor cell proliferation. Tα1 treatment induced a T helper (Th) 1 immune response in tumor metastases as evidenced by a significant increase of the Th1-specific markers IFN-γ and T-bet (1.21 ± 0.3 vs. 0.52 ± 0.08, p < 0.05; 0.88 ± 0.04 vs. 0.64 ± 0.14, p < 0.05, respectively). This Th1 skew was accompanied by increased CD8+ infiltration into omental and visceral metastases by Tα1 treatment compared to sham and HIPEC-treated animals (21.24 ± 2.16 vs. 10.45 ± 0.89 and 7.7 ± 1.3, p < 0.001; 14.12 ± 1.54 vs. 12.12 ± 0.01 and 6.64 ± 0.87, p < 0.01, respectively). CONCLUSIONS: Tα1 augments the effect of HIPEC by the induction of a Th1 anti-tumor immune response. Further experiments should evaluate Tα1 and other novel immunomodulators in order to exploit the immunological opportunities created by HIPEC.

Long-term functional and quality-of-life outcomes after IPAA in children.

BACKGROUND: The impact of IPAA on long-term outcomes in adults is favorable. Studies on functional outcome and quality of life in children are sparse. OBJECTIVE: The aim of this study was to evaluate the functional and quality-of-life outcomes after IPAA in children and to investigate the possible correlations between the two. DESIGN: Standardized validated questionnaires of bowel/psychosocial functioning and quality of life were used to assess outcome. SETTING: This study was conducted at a tertiary medical center. PATIENTS: All children who had surgery at <18 years of age and were followed up at our institute were included. Global Assessment of Function Scale questionnaires were used to evaluate functional outcome. Quality of life in patients >18 years at the time of follow-up was scored by using the Short Form 36 questionnaire completed by the patients. Quality of life in the younger patients at the time of follow-up was scored using the Child Health Questionarie-28 filled by the parents. RESULTS: Data were obtained in 26 patients (25 with a preoperative diagnosis of ulcerative colitis) at a median follow-up of 6 years. The median age at surgery was 15 years. Quality of life was comparable to the general population for children >18 at the time of follow-up in 7 of 8 items, but was lower than in the general population in 7 of 12 items for those who were younger at the time of follow-up. The mean functional score was found to be negatively correlated to all 8 Short Form 36 parameters (r > 0.5; p < 0.005), but only to one of the Child Health Questionarie-28 parameters. LIMITATIONS: This study was limited by its small sample size. CONCLUSIONS: The functional outcomes among pediatric patients undergoing IPAA are good. Parents' perception of their child's quality of life is poorer in comparison with the perception by patients themselves when older and with no correlation to the functional results.