Expression of thymidylate synthase in human gastric and colorectal adenocarcinomas is upregulated by p16/INK4.

BACKGROUND/AIMS: We observed the relationship between the expression of thymidylate synthase protein (pTS) and cell cycle regulators in gastric and colorectal adenocarcinoma tissues. METHODOLOGY: This study included 80 gastric and 50 colorectal adenocarcinomas. Immunohistochemical staining was performed using a polyclonal antibody to recombinant human pTS, and monoclonal antibodies to p53, p21/WAF1CIP1, p16/INK4, cyclin D1 and pRB. Each staining was quantified using computerized image analysis on a CAS 200 system. We selected the mean expression values as the cutoff values to distinguish between high and low expression of these substances. RESULTS: There was no relationship between pTS expression and p21/WAF1CIP1, cyclin D1, or pRB expression in gastric and colorectal carcinomas. In both gastric and colorectal carcinomas, the pTS expression was significantly low in the high p16/INK4 expression subgroup compared with the low p16/INK4 expression subgroup (P < 0.05). Further, the pTS expression was significantly high in the high p53 expression subgroup compared with the low p53 expression subgroup in colorectal adenocarcinomas (P < 0.05). CONCLUSIONS: pTS expression regulation in human gastric and colorectal adenocarcinomas in complex, and upregulated by p16/INK4.

[Significance of systemic inflammatory response syndrome after surgical treatment for thoracic esophageal cancer].

We studied the significance of Systemic Inflammatory Response Syndrome (SIRS) state after surgical treatment of thoracic esophageal cancer. From January 1991 to December 1995, 35 patients received thoracic esophageal cancer surgery. Thirty three patients (94.3%) were in the SIRS state after surgery and mean duration of SIRS was 3.4 days. Duration of SIRS was statistically longer in patients with pulmonary complications. Patients with hyperbilirubinemia (> or = 3.0 mg/dl) after surgery had longer duration of SIRS. Induction therapy did not affect the duration of SIRS. Collectively, duration of SIRS is an indication of complications, especially of pulmonary complications, after surgical treatment of thoracic esophageal cancer, and blood bililubin score after surgery correlates to duration of SIRS. These suggest that we must pay special attention to patients with long duration of SIRS or hyperbilirubinemia after thoracic esophageal surgery.

[Advantages and disadvantages of harmonic scalpel in thoracic surgery].

We evaluated the usefulness of Harmonic Scalpel in thoracic surgery. Harmonic Scalpel is an ultrasonically activated surgical device which can coagulate and cut the vessels or tissues. The instrument made thoracoscopic resection of the neurogenic tumor and the mediastinal lymph node and thoracoscopic sympatectomy safetier and easier, because it does not conduct an electric current to the nerve and has high ability of hemostasis. Harmonic Scalpel will be very useful device in the future if its shapes of blades or handpieces are improved.

[A case of mediastinal angiomyolipoma].

A 53-year-old woman was referred to our hospital for further evaluation of a mediastinal tumor. The tumor was diagnosed as a mediastinal angiomyolipoma by computed tomography and angiographic findings. Transarterial embolization was performed three times, then the tumor was completely organized. Although angiomyolipomas are often found in the kidney, those in the mediastinum are very rare. Angiomyolipoma is a benign tumor, then small asymptomatic tumor may be conserved. When the tumor is large in size and has a high risk of spontaneous rupture, arterial embolization is valuable for treatment of the tumor.

The number of 5-fluoro-2'-deoxyuridine-5'-monophosphate binding sites and reduced folate pool in human colorectal carcinoma tissues: changes after tegafur and uracil treatment.

Thymidylate synthase (TS) is a target enzyme of 5-fluorouracil and is inhibited by 5-fluoro-dUMP (FdUMP) to form an inactive ternary complex. We investigated the changes in the number of FdUMP binding sites in human colorectal carcinoma tissues after treatment with 5-fluorouracil derivatives and also examined the mechanisms underlying these changes. The number of FdUMP binding sites was significantly increased in patients who received tegafur and uracil preoperatively [UFT (+) group, n = 14] compared with those who did not [UFT (-) group, n = 36; P < 0.0001]. No amplification of the TS gene was observed in the carcinoma tissues in either group. The level of TS mRNA in the carcinoma tissues showed no significant difference between UFT (-) and UFT (+) groups. There was a significant correlation between the level of TS mRNA and TS in the UFT (-) group, as shown by simple linear regression analysis (P < 0.05). In the UFT (+) group, 9 of 12 cases showed TSf corresponding to their level of TS mRNA. It seemed that the augmentation of TStot is the result of accumulation of ternary complex. Thus, TS inhibition by FdUMP will be insufficient in the absence of methylenetetrahydrofolate in the cytosol, because translation of TS from TS mRNA has been shown to continue in the presence of FdUMP.

[Reoperation for recurrent and second primary lung cancer].

Thirty patients have undergone multiple resections for non-small cell lung cancer from 1973 to July 1994, constituting 2.6% of 1,153 who had undergone pulmonary resection for such tumor. In the 22 patients for recurrent cancer, 15 resections of the ipsilateral lung and 9 of the contralateral lung were performed with no operative death. The survival rate following second resection in 22 patients was 33.8% at 3 years and 13.5% at 5 years. Survival rate was poor in patients with DNA aneuploid primary tumor and there was not a patients of 5 years survival. Three out of the 5 patients which had a diploid pattern in the primary tumor, showed an aneuploid pattern in the recurrent tumor. Long survival patients were founded only in the patients which had a diploid primary tumor. In the 8 patients for second primary lung cancer, 4 resections of the ipsilateral lung and 4 of the contralateral lung were performed, including two bronchoplastic surgery for early hilar squamous cell carcinoma. The survival rate following second resection in 8 patients was 64.2% at 5 years with good result. We concluded that an aggressive surgical approach is safe and warranted in patients with second primary lung cancer.