Masahiro Kagabu

Neoadjuvant Chemotherapy Using Platinum-Based Regimens for Stage Ib2-II Squamous Cell Carcinoma and Non-Squamous Cell Carcinoma of the Cervix

The methods used for treating stage Ib2-IIb cervical cancers, with a bulky mass, differ between Japan and Western countries. In Western countries, concurrent chemoradiation (CCRT) has been recommended as a standard therapy for such tumors based on the results of multiple large-scale randomized trials and meta-analyses (Morris et al., 1999; Rose et al., 1999; Whitney et al., 1999; Pearcey et al., 2002; Eifel et al. 2004; Green et al. 2001; Lukka et al., 2002). In Japan, Korea, Italy and some other countries, the neoadjuvant chemotherapy (NAC) approach has been extensively introduced to clinical practice (Sugiyama et al., 1999). NAC is considered to be clinically significant in 2 respects: it is expected to improve the radicality and safety of surgery by reducing tumor size; and it is expected to exert systemic effects, i.e., effects on lymph node occult micrometastases, etc. A disadvantage of NAC is delayed initiation of the primary treatment, suggesting the necessity of completing NAC as an auxiliary therapy within a short period of time. Therefore, we may find that NAC is valuable if it can exert efficacy rapidly with high platinum dose intensity (DI), assuring that subsequent primary surgical therapy can be performed as soon as possible. At our facility, a platinum-based regimen has been used for NAC in patients with cervical cancer. Herein, we review the efficacy and safety data on NAC for squamous cell carcinoma of the uterine cervix. We previously reported our interim data and now present the results of an ongoing pilot study on the efficacy and safety of NAC for non-squamous cell carcinoma of the uterine cervix.

Mast cells partially contribute to mucosal adjuvanticity of surfactin in mice: Mast cells contribute to surfactin adjuvanticity

Surfactin (SF) is a cyclic lipopeptide that has potent mucosal adjuvant properties. However, immunological mechanisms of SF adjuvant action have not yet been elucidated. As some cyclic lipopeptides, such as polymyxin, can stimulate histamine release from mast cells, we hypothesized that mast cell activation is critical for SF adjuvanticity.

Pilot study of intraperitoneal administration of triamcinolone acetonide for cancerous ascites in patients with end-stage gynecological cancer.

Objective Patients with end-stage cancer have poorly controlled ascites retention resulting due to cancerous peritonitis. We intraperitoneally administered triamcinolone acetonide (TA) to patients with end-stage gynecological cancer as a pilot study, and our treatment results are reported herein. Patients and Methods We enrolled 26 patients with end-stage gynecological cancer requiring frequent abdominal paracentesis for ascites drainage between April 2010 and September 2012. The volume of ascites drainage was 2000 to 3000 mL per drainage session, and TA at 10 mg/kg was intraperitoneally administered after drainage. We compared abdominal paracentesis intervals, performance status (PS), total protein level, albumin level, white blood cell count, changes in C-reactive protein (CRP) level, and adverse events before and after TA use. Results Triamcinolone acetonide was administered to 26 patients for a total of 59 times. The abdominal paracentesis intervals, PS, and mean (SD) of C-reactive protein before and after TA use were 13.2 (12.6) days and 21.9 (23.6) days (P = 0.0117), 2.4 (0.7) and 1.6 (1.1) (P < 0.0001), and 7.5 (5.2) mg/dL and 5.5 (5.0) mg/dL (P = 0.007), respectively. With regard to adverse events, abdominal pain of grade 2 was observed once (1.7%), but there were no other acute adverse events. Four subjects (15.4%) had intestinal perforation. Conclusions Intraperitoneal administration of TA after drainage was considered to be a useful treatment, as it seems to extend paracentesis intervals and improve PS while maintaining quality of life for end-stage gynecological cancer patients with massive ascites.

Critical micelle concentration and particle size determine adjuvanticity of cyclic lipopeptides

Cyclic lipopeptides such as surfactin and polymyxin have potent mucosal adjuvant properties. Cyclic lipopeptides are tensioactive compounds, but the relationship between adjuvanticity and surface activity is unknown. Here, we show that the critical micelle concentration (cmc) of surfactant and particle size of the surfactant‐protein complex are important determinants of cyclic lipopeptide adjuvanticity. We found that the diameter of cyclic lipopeptide‐ovalbumin (OVA) complex particles was significantly larger than that in the solutions of OVA alone at cyclic lipopeptide concentrations above the cmc. OVA‐specific antibody titres in mice immunized intranasally with OVA and a cyclic lipopeptide at concentrations above its cmc were significantly higher than those in mice immunized with OVA plus the same dose of the cyclic lipopeptide but administered with formulations in which cyclic lipopeptide concentration was below the cmc. Thus, the concentration of the cyclic lipopeptide in the formulation at immunization, but not its overall dose, was critical for its adjuvanticity. Furthermore, two types of aggregates, the cyclic lipopeptide simplex micelles and the cyclic lipopeptide‐OVA complex micelles, were found in formulations with SF concentrations above its cmc. Degranulation of mast cells exposed to SF simplex micelles was more pronounced when SF concentration was above the cmc. In conclusion, our study showed that surface activity properties, such as the cmc and the size of surfactant‐protein complex, contribute to the adjuvanticity of cyclic lipopeptides. Our study proposes a novel idea that cmc is a key parameter for tensioactive adjuvants.

A retrospective study of neoadjuvant chemotherapy plus radical hysterectomy versus radical hysterectomy alone in patients with stage II cervical squamous cell carcinoma presenting as a bulky mass

Objective In order to evaluate the usefulness of neoadjuvant chemotherapy (NAC) for stage II cervical squamous cell carcinoma with a bulky mass, we retrospectively compared patients receiving NAC followed by radical hysterectomy (RH; NAC group) with patients who underwent RH without NAC (Ope group). Patients and methods The study period was from June 2002 to March 2014. The subjects were 28 patients with a stage II bulky mass in the NAC group and 17 such patients in the Ope group. The chi-square test was used to compare operative time, volume of intraoperative blood loss, use of blood transfusion, and time from surgery to discharge between the two groups. Moreover, the log-rank test using the Kaplan–Meier method was performed to compare disease-free survival (DFS) and overall survival (OS) between the groups. Results There were no statistically significant differences between the two groups in operative time, volume of intraoperative blood loss, or use of blood transfusion. However, the time from surgery to discharge was 18 days (14–25 days) in the NAC group and 25 days (21–34 days) in the Ope group; the patients in the NAC group were discharged earlier (P=0.032). The hazard ratio for DFS in the NAC group as compared with that in the Ope group was 0.36 (95% CI 0.08–0.91), and the 3-year DFS rates were 81.2% and 41.0%, respectively (P=0.028). Moreover, the hazard ratio for OS was 0.39 (95% CI 0.11–1.24), and the 3-year OS rates were 82.3% and 66.4%, respectively (P=0.101). Conclusion NAC with cisplatin and irinotecan was confirmed to prolong DFS as compared with RH alone. The results of this study suggest that NAC might be a useful adjunct to surgery in the treatment of stage II squamous cell carcinoma presenting as a bulky mass.