Y. Hashiguchi

Interleukin-6 and stress hormone responses after uncomplicated gasless laparoscopic-assisted and open sigmoid colectomy

PURPOSE: Laparoscopic colectomy has increasingly been advocated as an option for treatment of colonic disease. The purpose of this study was to compare effects of laparoscopicassisted sigmoid colectomy (LAS) and conventional open colectomy (OPEN) on postoperative cytokine and stress hormone responses. METHODS: Fourteen patients with sigmoid colon cancer, apparently free of preoperative complications, were analyzed. Patients in both groups underwent sigmoid colectomy with lymphadenectomy. LAS was performed by the gasless abdominal wall-lifting method. A 5 cm incision was placed at the beginning of the operation. Blood samples were taken preoperatively and postoperatively for measurement of interleukin-6, glucagon and C-reactive protein. Urinary catecholamine excretions were also determined postoperatively. RESULTS: The two groups of patients were similar with respect to age (61±7 for LASvs.64±9 for OPEN) and sex. Intraoperative blood loss did not differ significantly between groups (112±97 ml for LASvs.366±380 ml for OPEN). Operative times for LAS tended to be longer than those for OPEN (231±67vs.169±45 minutes;P=0.08). Similar time courses of postoperative interleukin-6, C-reactive protein, and stress hormone responses were observed in both groups. No significant differences were observed in the magnitude of changes except that the serum interleukin-6 level on day of surgery (postoperative day 0) was significantly higher in LAS patients than in those receiving OPEN. In addition, interleukin-6 levels showed a significant positive correlation with operative duration (r=0.582;P<0.05). CONCLUSIONS: Data suggest that stress responses after sigmoid colectomy, in patients undergoing LAS, are comparable with those of patients receiving OPEN and that the early interleukin-6 response after surgery appears to be associated with operative time.

GROWTH HORMONE AND INSULIN-LIKE GROWTH FACTOR I AUGMENT ESCHERICHIA COLI-KILLING ACTIVITY OF MURINE PERITONEAL EXUDATIVE CELLS

Effects of growth hormone (GH) and insulin-like growth factor (IGF)-I on Escherichia coli-killing activity of murine peritoneal exudative cells (PECs) were investigated. Plasma from the mice, injected subcutaneously with saline, GH (4.8 mg/kg/day), or IGF-I (24 mg/kg/day) for 6 days, was mixed with E. coli and pooled murine PECs. Plasma from GH- and IGF-l-treated mice modestly but significantly augmented the E. co//-killing activity of PECs, as compared with that from saline controls. Plasma from IGF-l-treated mice also enhanced PEC interleukin 1 production. In the next experiment, PECs preincubated with medium, GH (10–1000 ng/mL), or IGF-I (50–5000 ng/mL) for 3 h were investigated for E co//-killing activity. Preincubation of PECs with all concentrations of GH and IGF-I significantly enhanced the E. co//-killing activity of PECs, as compared with the medium control. These results indicate that GH and IGF-I enhance phagocytosis and the E. co//-killing activity of PECs, via a modestly increased plasma capacity to support these activities, as well as by a strong direct action.

Effects of growth hormone and insulin-like growth factor 1 (IGF-1 ) on hepatic IGF-1-mRNA, plasma IGF-1 and nitrogen excretion in gastrectomized rats with liver cirrhosis

The growth hormone (GH)-insulin-like growth factor 1 (IGF-1) axis is impaired in liver cirrhosis. We determined the effects of GH and IGF-1 treatments in gastrectomized rats with thioacetamide-induced cirrhosis. GH did not increase hepatic IGF-1-mRNA, plasma IGF-1 or the tissue, i.e. gastrocnemius muscle IGF-1 level. IGF-1 administration increased plasma IGF-1 without increasing hepatic IGF-1-mRNA. GH and IGF-1 independently decreased postoperative urinary nitrogen excretion. We conclude that both GH and IGF-1 improve postoperative nitrogen metabolism. Furthermore, GH may exert its anabolic effects directly and/or via actions mediated by IGF-1 production, other than in the liver and in the skeletal muscle, in the setting of cirrhosis.

Alteration of tumor markers may predict survival in colorectal cancer patients treated with TAS-102 or regorafenib as salvage-line chemotherapy: a single-institutional experience

Objectives: TAS-102 and regorafenib are novel antineoplastic drugs recommended for salvage-line chemotherapy. The objective of this study was to elucidate useful markers with predictive values for the effectiveness of these drugs. Methods: Between August 2013 and April 2016, 23 patients with refractory colorectal cancer received salvage-line chemotherapy at Teikyo University Hospital, Japan. 15 patients received TAS-102 monotherapy and 15 received regorafenib, including seven who had dual therapies. Tumor markers were analyzed for possible correlations with tumor response and the patients’ prognoses after these treatments. Results: Twelve patients of each group had radiologically measurable tumors. None of the TAS-102-treated patients achieved complete response (CR) or partial response (PR). After regorafenib therapy, no patients achieved CR, but one (8%) patient showed PR. These and the lack of correlation between the tumor responses and the patients’ overall survival (OS) suggested a limited predictive value of RECIST-based tumor evaluation in our study. Nonetheless, the OS of the patients with a decreased CA19-9 level after initial treatment with TAS-102 tended to be longer than that of the patients with an increased CA19-9 level (p=0.058). The OS of the patients with decreased CEA after initial regorafenib treatment was significantly longer than that of patients with increased CEA (p=0.03). Conclusions: The results of the present analysis suggest that CEA and CA19-9 may be more practical and useful as predictive/prognostic markers for refractory CRC patients treated with TAS-102 and regorafenib even when the predictive value of the tumor response measured using RECIST is not clear. Correspondence to: Keiji Matsuda, M.D., Ph.D., The Department of Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, Japan, Tel: 81-3-3964-1211; Fax: 81-3-5375-6097; E-mail: keiji@med.teikyo-u.ac.jp