Takeshi Nezu

Immunomodulatory effects of low dose cis-Diaminedichloroplatinum (cisplatin) combined with UFT and PSK in patients with advanced colorectal cancer.

It is well known that cell-mediated immunity is suppressed in patients with neoplastic diseases. We have reported that soluble receptors for interleukin-2 (sIL-2R) and tumor necosis factor (sTNF-R1) are elevated in the serum of patients with advanced colorectal cancer. The presence of these soluble receptors and immunosuppressive cytokines, including interleukin-10 (IL-10), might be important in the mechanisms of immunosuppression. cis-Diaminedichloroplatinum (cisplatin) has been reported to immunomodulate, especially when used in low dose in combination with 5-Fluorouracil (5-FU). In this study, cisplatin and UFT, a form of uracil and tegafur which is a prodrug of 5-FU, were administered with immunomodulator Polysaccharide K (PSK) to ten patients with colorectal cancer, who showed distant metastasis in the liver or lung, and the serum levels of sIL-2R and sTNF-R1 and the production of γ-interferon (γ-INF) and interleukin-10 by peripheral blood mononuclear cells were measured. The serum concentrations of sIL-2R and the production of IL-10 were reduced (p<0.05) after 2 months of treatment. Thus, this combination appeared to have immunomodulative potential in patients with advanced colorectal cancer.

Clinical Potential of Biological Response Modifiers Combined with Chemotherapy for Gastric Cancer

The most effective treatment for gastric cancer is complete surgical resection with lymphadenectomy. However, a number of patients experience recurrence of the cancer even after curative surgery. This review focuses on comparative trials studying the use of adjuvant therapy with chemotherapy plus immunotherapy in the treatment of patients with curatively resected gastric cancer. Preoperative and intraperitoneal therapy, and therapy for advanced or recurrent gastric cancer are also discussed. At present, some subset analyses of adjuvant trials have shown favorable results suggesting that the biological response modifiers (BRMs), PSK or OK-432, add a benefit to chemotherapy. For advanced gastric cancer, although gastric cancer cells are generally not very sensitive to most of the currently available chemotherapeutic agents, it has been reported that biochemical modulation with treatments including low-dose cisplatin + 5-FU (fluorouracil) have high response rates and exert an immunomodulatory effect especially when used in combination with BRMs. The impact of splenectomy and some of the promising newly developed drugs are discussed.

Elevated serum concentration of interleukin-1 receptor antagonist (IL-1ra) is correlated to interleukin-6 and to hypoalbuminemia in cachectic patients with colorectal cancer

AbstractBackground. The mechanisms leading to the development of cancer cachexia are still not well understood. Some important factors, including cytokines and growth factors, are involved, and recently, cytokines such as interleukin-1 and interleukin-6 have been reported to be involved as mediators of this disorder. Methods. In patients with colorectal cancer, serum concentrations of interleukin-1 receptor antagonist (IL-1ra) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA) and analyzed in relation to the patients nutrition (in terms of albumin concentration [percentage of total protein] in the serum) and the tumor load. Results. The concentration of IL-1ra was significantly increased in cachectic patients compared with that in healthy volunteers and in the non-cachectic patients, and the concentration was correlated to the serum concentration of IL-6 and inversely correlated to the concentration of albumin (%). These concentrations, however, did not correlate to levels of tumor markers tested, ie, carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19-9. Conclusion. It was shown that the serum concentration of IL-1ra was a useful indicator for cancer cachexia and hypoalbuminemia; IL-1ra seems to be produced by immune-regulating host cells rather than by neoplastic cells.

Laparoscopic treatment for common bile duct stones by transcystic papilla balloon dilatation technique

Abstract. The laparoscopic transcystic common bile duct (CBD) approach is becoming increasingly more refined as an ideal technique to deal with gallbladder stones (GBS) and common bile duct stones (CBDS) during a single operation. Our method, transcystic CBD exploration and papilla balloon dilatation (PBD), is an easier, safer, and less invasive technique than the transcystic approaches that have previously been reported. With our method, a sheath is introduced through the cystic duct into the CBD in order to allow catheter exchange, and the CBDS is flushed out through the papilla into the duodenum after PBD. We applied our new technique, without complication, to a patient with GBS and CBDS. Our technique is one of the safest, easiest, and least invasive methods for the treatment of patients with GBS and CBDS.