Postsurgical sequential methotrexate/5-FU and leucovorin on outpatient basis for advanced colorectal carcinoma.

BACKGROUND/AIMS: The present study compared the effects of sequential methotrexate and 5-fluorouracil followed by leucovorin rescue (MFL), as an adjuvant chemotherapy versus a combination of UFT and mitomycin C (MMC), on patient survival and recurrence after surgery for colorectal carcinoma. METHODOLOGY: Between January 1990 and December 1997, a total of 55 patients with advanced colorectal cancer were treated postsurgically by adjuvant chemotherapy using MFL or UFT-MMC. Surgical treatment was performed according to standardized procedures for radical resection of colorectal cancer. The patients were divided into 2 groups after surgery. The MFL regimen consisted of MTX (100 mg/m2) and 5-FU (600 mg/m2) at hour 24, followed by leucovorin rescue. The UFT-MMC regimen consisted of MMC (12 mg/m2) intraoperatively and MMC (6 mg/m2) every other week after surgery for 2 months, and oral UFT (375 mg/m2/day), a combination of tegafur and uracil in a molar ratio of 1:4, was continued for 3 years or longer depending on the patients tolerance. RESULTS: The overall survival rates after surgery were significantly (P < 0.05) higher in the MFL than the UFT-MMC group. Recurrence rates were significantly lower in the MFL than the UFT-MMC group, especially for liver recurrence. Disease-free survival was significantly (P < 0.05) higher in the MFL than the UFT-MMC group. CONCLUSIONS: These results demonstrated the superiority of MFL therapy for improving postsurgical survival in patients with advanced colorectal cancer, in particular those patients with a high risk of recurrence following potential curative resection.

Sigmoid colon diverticulosis adherent to mesh plug migration after open inguinal hernia repair.

PURPOSE: Tension-free hernia repair with polypropylene mesh plug and patch is currently the most popular technique for open inguinal hernioplasty. It is well tolerated by most patients with few complications. Despite these excellent results, late-onset complications may occur. METHODS: An 83-year-old man reported 2 weeks of bloody stool. His medical history was significant for a left open inguinal herniorrhaphy with the mesh plug and patch technique. Barium enema revealed a stenotic segment in the sigmoid colon and multiple diverticulosis. Because a malignant lesion could not be ruled out, the patient underwent an operation. Laparotomy revealed an inflamed sigmoid colon with diverticulosis adherent to a hard tumor, which was mesh plug used for the previous open inguinal hernia repair. After mobilization of the adhesion between the mesh plug tumor and the sigmoid colon, sigmoidectomy was performed. The patient's postoperative course was uneventful. CONCLUSIONS: We reported a case of sigmoid colon diverticulosis adherent to mesh plug migration after open inguinal hernia repair. The potential risk of plug migration should be well understood by the surgeon. To avoid this risk completely, several methods have been proposed such as suturing the plug and patch together, or using an all-in-one design such as the Prolene Hernia System (Johnson and Johnson Co., Tokyo, Japan).

Postsurgical sequential methotrexate, fluorouracil, and leucovorin for stages 3 and 4 gastric carcinoma: A preliminary study.

BACKGROUND AND OBJECTIVES: The present study compared the effects of sequential methotrexate and fluorouracil followed by leucovorin rescue (MFL), as an adjuvant chemotherapy vs. UFT (a combination of uracil and tegafur), on patient survival and recurrence following surgery for advanced gastric carcinoma. METHODS: Between July 1990 and June 1998, a total of 54 patients with advanced gastric cancer were treated postoperatively by adjuvant chemotherapy using MFL or UFT. Surgical treatment was performed according to standardized procedures for radical resection of gastric cancer. The patients were stratified into two groups following surgery. The MFL regimen consisted of methotrexate (100 mg/m2) and 5-fluorouracil (600 mg/m2) at hour 3, followed by leucovorin rescue. The oral UFT (375 mg/m2/day), a combination of tegafur and uracil in a molar ratio of 1:4, was continued for 3 years or longer depending on the patients tolerance. RESULTS: In stage 3 gastric cancer, the overall survival rates following surgery was significantly (p < 0.05) higher in the MFL than the UFT group. Difference in disease free survival was not statistically significant between the groups. Recurrence rates showed a trend (p = 0.08) to decrease in the MFL than the UFT group. In stage 4 gastric cancer, no significant difference was obtained in the overall survival rates between the groups. CONCLUSIONS: The present results suggested the superiority of MFL treatment for improving postoperative survival in patients with advanced gastric cancer, in particular for those patients with a high risk of recurrence following potential curative resection. In patients with stage 4 gastric cancer, however, MFL treatment showed similar effects as UFT on the postsurgical survival of the patients.

A case of colon cancer recurrence with P-glycoprotein treated by methotrexate, fluorouracil, and leucovorin.

A 68 year-old female underwent right hemicolectomy for an advanced cecum cancer and had been well without any evidence of recurrence for a year after surgery. Despite post-operative treatment with oral Tegafur (400 mg/m2/day), CEA level increased gradually beginning 15 months after surgery. Sequential chemotherapy with methotrexate (MTX) and 5-Fluorouracil (5-FU), followed by leucovorin rescue (MFL) was started on an outpatient basis, and has been continued every 4 weeks since then. It consisted of MTX (100 mg/m2) and 5-FU (600 mg/m2) started 24 hours after MTX, followed by oral leucovorin (15 mg/body) started 30 hours after MTX 6 times at intervals of 6 hours. CEA level declined initially, but increased slowly for 3 years on MFL, although no evidence of recurrence was detected by imaging studies with computed tomography, ultrasound, and scintigram. Four years after surgery, a tumor recurrence developed in the abdominal wall. The patient underwent resection of the tumor, resulting in a decline of the CEA level. She has been alive and well for 5 years on MFL after the primary surgery. Both the original tumor and recurrent tumor showed immunoreactivity for P-glycoprotein. The present case demonstrates the feasibility of using MFL on an outpatient basis, and its potential to suppress the colon cancer growth with P-glycoprotein expression.

Postsurgical sequential methotrexate, fluorouracil, and leucovorin for advanced colorectal carcinoma: a preliminary study.

BACKGROUND AND OBJECTIVES: The present study compared the effects of sequential methotrexate and fluorouracil followed by leucovorin rescue (MFL), as an adjuvant chemotherapy versus a combination of tegafur (UFT) and mitomycin C (MMC), on patient survival and recurrence after surgery for colorectal carcinoma. METHODS: Between January 1990 and December 1995, a total of 46 patients with advanced colorectal cancer were treated postsurgically by adjuvant chemotherapy using MFL or UFT-MMC. Surgical treatment was performed according to standardized procedures for radical resection of colorectal cancer. The patients were stratified into two groups after surgery. The MFL regimen consisted of MTX (100 mg/m2) and 5-FU (600 mg/m2) at hour 24, followed by leucovorin rescue. The UFT-MMC regimen consisted of MMC (12 mg/m2) intraoperatively and MMC (6 mg/m2) ever other week after surgery for 2 months and oral UFT (375 mg/m2/day), a combination of tegafur and uracil in a molar ratio of 1:4, was continued for 3 years or longer depending on the patients tolerance. RESULTS: The overall survival rates after surgery was significantly (P < 0.05) higher in the MFL than the UFT-MMC group. Recurrence rates were significantly lower in the MFL than the UFT-MMC Group, especially for liver recurrence. Disease-free survival was significantly (P < 0.05) higher in the MFL than the UFT-MMC group. CONCLUSIONS: The present results demonstrated the superiority of MFL therapy for improving postsurgical survival in patients with advanced colorectal cancer, in particular for those patients with a high risk of recurrence following potential curative resection.

Increase of vascular endothelial growth factor mRNA expression by 1,25-dihydroxyvitamin D3 in human osteoblast-like cells.

Vascular endothelial growth factor (VEGF), a secreted endothelial cell-specific mitogen, is produced in endocrine organs and regulated by trophic hormones. Because angiogenesis and osteogenesis are closely regulated, we studied whether human osteoblast-like cells produce VEGF, and if so, what factors regulate VEGF mRNA expression. Human osteoblast-like cells (HObLC) derived from trabecular bone explants were cultured in alpha-MEM supplemented with 10% fetal calf serum. Northern blot analysis revealed that HObLC expressed VEGF mRNA, as did several human osteosarcoma cells. 1,25-(OH)2D3 increased the steady-state levels of VEGF mRNA in a time- and concentration-dependent manner in HObLC and one of the osteosarcoma cell lines, SaOS-2, accompanied by an increase in the concentration of immunoreactive VEGF in the conditioned medium. PTH and IGF-I also increased the level of VEGF mRNA in HObLC and SaOS-2 cells. Furthermore, 12-O-tetradecanoylphorbol ester stimulated VEGF mRNA in a time-and concentration-dependent manner. The VEGF mRNA expression induced by 1,25-(OH)2D3 was completely inhibited by H-7, but only partially by staurosporine. We have demonstrated that PTH, IGF-I, and most potently 1,25-(OH)2D3 stimulate the mRNA expression and secretion of VEGF in human osteoblast-like cells, suggesting that one of the anabolic effects of 1,25-(OH)2D3 on skeletal tissue may be mediated by VEGF produced by osteoblasts.

Intraperitoneal administration of Senegae Radix extract and its main component, senegin-II, affects lipid metabolism in normal and hyperlipidemic mice.

The hypolipidemic effect of Senegae Radix, i.e. "Senega," was investigated in normal and hyperlipidemic mice. The n-butanol fraction of the methanol extract of Senegae Radix (SN) (5 mg/kg) significantly reduced the blood triglyceride level of normal mice 7 h after intraperitoneal administration (p < 0.05) and also significantly reduced the blood triglyceride level of cholesterol-fed mice under similar conditions (p < 0.05). SN (5 mg/kg) also reduced the blood triglyceride and cholesterol levels after repeated administration to cholesterol-fed mice. SN also decreased the blood triglyceride level in Triton-induced hyperlipidemia. It is suggested that this fraction contains one or more hypolipidemic components including the main triterpenoid glycoside, senegin-II, which significantly reduces the levels of blood triglycerides in normal mice.

Human sperm nuclei can transform into condensed chromosomes in Xenopus egg extracts.

The conditions necessary for inducing pronucleus formation and chromosome condensation of human sperm nuclei were studied using Xenopus egg extracts. When lysolecithin (LC)-and dithiothreitol (DTT)-treated spermatozoa were incubated with egg extract prepared with an extraction medium containing 10 mM EGTA, sperm nuclei transformed into chromosomes, bypassing the pronuclear stage. On the contrary, LC-DTT-treated spermatozoa incubated in egg extract without EGTA mimicked LC-permeabilized Xenopus spermatozoa in that they underwent pronucleus formation accompanied by DNA synthesis and subsequent chromosome condensation in the correct chronological order. These observations suggest the importance of intracellular calcium for regulating the states of nuclear chromatin. LC-permeabilized human spermatozoa were not responsive to the egg extract without any additives, but formed pronuclei when incubated with the egg extract supplemented with 5-10 mM DTT. However, subsequent chromosome condensation of sperm nucleus did not occur in the DTT extract. This suggests that disulfide-reducing agent blocks transformation of sperm pronuclei into condensed chromosomes.