Polysaccharide-K (PSK) may suppress surgical stress-induced metastasis in rat colon cancer.

PURPOSE: We previously demonstrated that hepatic ischemia and reperfusion (I/R) injury increased liver metastasis and cancer growth of RCN-H4 cells. Using a rat model of hepatic I/R-induced liver metastasis, we investigated the metastasis-suppressing effect of polysaccharide-K (PSK), a biological response modifier composed of protein-bound polysaccharide. METHODS: Fischer rats underwent 60 min of 70% partial hepatic ischemia. After 60 min of reperfusion, rat colon adenocarcinoma cells (RCN-H4) were inoculated intrasplenically. PSK was administered orally before I/R, after I/R, or before and after I/R. The weights of metastatic lesions of the liver or the numbers of liver metastatic nodules were determined on day 21. The effect of PSK on angiogenesis was studied by a rat cornea model using RCN-H4 cells or a vascular endothelial growth factor (VEGF)-containing pellet and an in vitro VEGF-induced endothelial cell migration assay. RESULTS: PSK administration significantly (p < 0.05) suppressed the I/R-induced increase in hepatic metastasis of RCN-H4 cells. The suppression of I/R-promoted metastasis was observed irrespective of the timing of administration. Furthermore, PSK significantly suppressed angiogenesis induced by RCN-H4 cells (p < 0.05) and the VEGF pellet (p < 0.01). PSK significantly suppressed the VEGF-induced migration of vascular endothelial cells (p < 0.05). CONCLUSION: PSK may suppress metastasis induced by hepatic I/R. The suppression of angiogenesis by PSK may be one of the mechanisms of the inhibition of hepatic metastasis.

A case of pathological complete response of advanced rectal cancer to preoperative chemoradiotherapy using S-1.

In patients with advanced rectal cancer, preoperative chemoradiotherapy is superior to postoperative chemoradiotherapy because of causing less toxicity and achieving higher rates of sphincter preservation and curative resection. We treated a patient who had advanced rectal cancer with preoperative chemotherapy using S-1 and concurrent radiotherapy. S-1 was orally administered at a dose of 100 mg/day during the first cycle (two-week on and one week off). During the third cycle, radiotherapy was initiated concurrently and a total dose of 45 Gy was given. The most severe adverse event was grade 3 leukopenia during the third cycle. On day 42 after completing radiotherapy, low anterior resection with diverting colostomy was performed. Histological examination found no viable cancer cells in the resected specimens, including the primary tumor site and lymph nodes. Thus, a pathological complete response was achieved. Postoperatively, anastomotic leakage occurred, but it was resolved with transanal drainage. Preoperative chemoradiotherapy using S-1 contributed to sphincter preservation and curative resection in this patient. This regimen was both effective and well-tolerated, suggesting that it could be useful for advanced rectal cancer.

Hepatic ischemia-reperfusion increases vascular endothelial growth factor and cancer growth in rats.

BACKGROUND: In liver surgery, the hepatic pedicle often is clamped to reduce blood loss, and later unclamped, representing hepatic ischemia and reperfusion (I/R) with induction of hypoxia. Vascular endothelial growth factor (VEGF) expression reportedly is induced by hypoxia; further, some cancer cells express the VEGF receptor (flt-1, flk-1/KDR). We hypothesized that I/R-induced VEGF expression could enhance growth of microscopic tumor via VEGF receptors on tumor cells, thus promoting liver metastasis in a rat model. MATERIALS AND METHODS: Time-dependent VEGF expression in liver and plasma was determined by enzyme-linked immunosorbent assay in rats subjected to 60 min of 70% hepatic I/R (I/R group). Other rats given an intrasplenic inoculation of a rat colon adenocarcinoma cell line (RCH-H4) were divided 3 days later into three groups: group A, untreated; group B, sham operation; group C, 70% I/R for 60 min. Liver metastasis was evaluated on day 14. Expression of flt-1 and flk-1/KDR was examined in RCN-H4 cells, and effects of exogenous VEGF on RCN-H4 cell proliferation were determined by MTT assays. RESULTS: Hepatic VEGF expression increased significantly in the I/R group compared to the control group. Liver metastasis was more extensive in group C than in groups A and B. RCN-H4 cells expressed flt-1 and flk-1/KDR, while exogenous VEGF increased RCN-H4 cell proliferation. CONCLUSION: Hepatic ischemia reperfusion leads to induction of VEGF and this is associated with increased tumor burden in an animal model of colon cancer metastasis.

Localized giant inflammatory polyposis of the ileocecum associated with Crohn's disease: report of a case.

Although inflammatory polyposis is one of the common complications in patients with inflammatory bowel disease, it is rare that each poly grows up to more than 1.5 cm. We describe a case of localized giant inflammatory polyposis of the ileocecum associated with Crohn's disease. A 40-year-old man who had been followed for 28 years because of Crohn's disease was hospitalized for right lower abdominal pain after meals. Barium enema and colonoscopy showed numerous worm-like polyps in the ascending colon which grew up to the hepatic flexure of the colon from the ileocecum, causing an obstruction of the ileocecal orifice. Since histology of a biopsy specimen taken from the giant polyps showed no dysplasia, he was diagnosed with ileus due to the localized giant inflammatory polyposis. A laparoscopically assisted ileocecal resection was performed. The resected specimen showed that the giant polyps grew up into the ileocecum. Histological examination revealed inflammatory polyposis without neoplasm. Generally, conservative treatment is indicated for localized giant inflammatory polyposis because this lesion is regarded as benign. However, occasionally serious complications arise, requiring surgical treatment.

Edaravone reduces ischemia-reperfusion injury mediators in rat liver.

BACKGROUND: In hepatic ischemia-reperfusion (I/R) injury, oxidative stress both directly injures the liver and promotes an inflammatory reaction by up-regulating various inflammatory mediators. We investigated whether edaravone, a new hydroxy radical scavenger, could reduce hepatic I/R injury including expression of inflammatory mediators such as cytokines and adhesion molecules. MATERIALS AND METHODS: Male Sprague-Dawley rats were subjected to 30 min of partial hepatic pedicle clamping (70%) followed by reperfusion. Just after initiation of reperfusion and again 1 h later, edaravone was administered intraportally. After reperfusion hepatic lipid peroxidation was measured by thiobarbituric acid assay, and hepatic injury was quantified by measuring hepatic enzymes in plasma. We serially quantified hepatic expression of mRNAs for tumor necrosis factor (TNF)-alpha and E-selectin, and histologically examined E-selectin expression and neutrophil accumulation. RESULTS: In the edaravone group, hepatic lipid peroxidation and hepatic enzyme leakage were significantly less than in the saline group. Hepatic expression of TNF-alpha and E-selectin mRNAs was significantly lower in the edaravone than the saline group, at 2 h after initiation of reperfusion. Histologically, E-selectin immunoreactivity and neutrophil accumulation were less evident in hepatic sections from the edaravone group. CONCLUSIONS: Edaravone reduced hepatic I/R injury by minimizing oxidative stress, and inhibited subsequent injurious inflammation by reducing expression of inflammatory cytokines and adhesion molecules.

Intermittent hepatic ischemia-reperfusion minimizes liver metastasis in rats.

BACKGROUND: Surgical stresses, including hepatic ischemia-reperfusion (I/R), promote cancer growth and metastasis. We have reported that continuous hepatic I/R increases liver damage and promoted liver metastasis from colon cancer, whereas intermittent I/R causes less liver damage. We therefore examined whether intermittent I/R could reduce liver metastasis in a rat model. MATERIALS AND METHODS: Adult male Fischer rats was divided between three groups: group A (control), which received laparotomy for 120 min with no liver ischemia; group B (continuous I/R), which received 60 min of 70% partial liver ischemia followed by 60 min of reperfusion; and group C (intermittent I/R), which received 15 min of 70% ischemia and 15 min of reperfusion, repeated four times. Just before closing the abdomen, all animals were inoculated intrasplenically with rat colon adenocarcinoma cells (RCN-H4). Tumor nodules on the liver surface were counted 3 weeks later. In addition, expression of E-selectin mRNA in liver was examined at 1, 3, and 6 h after completing I/R by a reverse transcription-polymerase chain reaction. RESULTS: Continuous I/R (B) greatly promoted liver metastasis in both ischemic and nonischemic liver lobes, whereas intermittent I/R (C) showed significantly fewer metastasis than group B in both lobes. Significantly less E-selectin mRNA was expressed in group C than in group B. CONCLUSIONS: Intermittent I/R limits expression of E-selectin mRNA and liver metastasis. Intermittent hepatic I/R is less stressful than continuous I/R, minimizing liver metastasis by colon cancer cells through avoidance of E-selectin up-regulation.