Wataru Ichikawa

Depth of invasion parallels increased cyclooxygenase‐2 levels in patients with gastric carcinoma

Nonsteroidal anti‐inflammatory drugs may reduce the incidence of intestinal carcinoma, presumably through inhibition of cyclooxygenase‐2 (COX‐2). The authors correlated tumor expression of COX‐2 with clinicopathologic features in tissues from patients with gastric carcinoma.

Alterations and hypermethylation of the p14ARF gene in gastric cancer

p14ARF, generated through an alternative splicing process that replaces the first exon, 1α, of p16INK4a with exon 1β, located >15 kb upstream of exon 1α, has been shown to function as a growth suppressor. We examined 11 gastric cancer cell lines for mRNA expression, homozygous deletion, mutation, and promoter methylation of the p14ARF gene. No mRNA expression was detected in 5 of the 7 diffuse‐type cell lines. All intestinal cell lines displayed normal levels of expression except for one with a low level of expression. Of the 5 cell lines without expression, 3 (MKN45, NUGC‐2, and NUGC‐4) and 1 (KATO III) displayed homozygous deletion and methylation of the p14ARF gene, respectively. No mutation was found in the whole coding region of the p14ARF gene in 8 cell lines without homozygous deletion. Our results indicate that the p14ARF gene is more frequently inactivated by homozygous deletion or methylation in diffuse‐type gastric cancer cell lines (5/7, 71.4%) than in intestinal ones (0/4, P = 0.022). When we also analyzed 62 primary gastric cancers for the methylation status of the p14ARF promoter region, the methylation frequency tended to be higher in diffuse‐type gastric cancers (15/33, 45.5%) than in intestinal ones (7/28, 25%). Thus, p14ARF alterations might be involved in diffuse‐type gastric carcinogenesis. Int. J. Cancer 87:654–658, 2000.

Expression of cyclooxygenase-2 (COX-2) mRNA in human colorectal adenomas

Cyclooxygenase-2 (COX-2) is an important target for the suppression of colorectal tumorigenesis by non-steroidal anti-inflammatory drugs (NSAIDs). To evaluate the role of COX-2 in human sporadic colorectal adenomas, COX-2 mRNA expression was examined by reverse transcription-polymerase chain reaction (RT-PCR) in 63 adenomas. COX-2 mRNA was detected in all the adenomas at higher levels than in normal colorectal mucosa (P<0.001). Levels of expression in the adenomas were correlated with their size (P=0.019), but no relationships were demonstrable between COX-2 expression and adenoma location, macroscopically observed configuration or microscopic degree of dysplasia. These findings suggest that COX-2 plays an important role in the growth of sporadic colorectal adenomas.

Positive Relationship between Expression of CD44 and Hepatic Metastases in Colorectal Cancer

This study was performed to determine the relationship between the expression of CD44, p53 and NM23 and the metastatic potential of colorectal cancer. Frozen sections of 56 cases of colorectal cancer were immunohistologically examined for the expression of CD44, p53 and NM23. Positive immunoreactivity was found in 30 of 56 cases (54%) in CD44, 26 of 56 (46%) in p53 and 20 of 56 in NM23 (36%), respectively. There was no significant relationship between the expression of these molecules and clinicopathological findings such as age, sex, size, location of tumor, histological type, serosal invasion, peritoneal dissemination, lymph node metastasis, extramural venous spread and tumor stage; however, when examining the relationship between the expression of these molecules and prognosis in terms of hepatic metastasis and recurrence after curative operation, a significant association was seen in the expression of CD44, but none in p53 and NM23. It was suggested that expression of CD44 could be used as a possible indicator to predict metastatic potential of colorectal cancer.

Is lymphadenectomy needed for all submucosal gastric cancers

OBJECTIVEnTo find out if it is feasible to extend the indication for local resection of submucosal gastric cancer without increasing the risk of lymph node metastases.nnnDESIGNnRetrospective study.nnnSETTINGnUniversity hospital, Japan.nnnSUBJECTSn104 patients with gastric cancer confined to the submucosal layer who underwent conventional gastrectomy with lymphadenectomy.nnnINTERVENTIONSnThe risk of nodal metastases was analysed retrospectively depending on the depth of submucosal invasion, size of the tumour, and other clinicopathological findings.nnnMAIN OUTCOME MEASURESnThe degree of submucosal invasion, size of the tumour, and incidence of lymph node metastasis.nnnRESULTSn15/104 patients (14%) had lymph node metastases. No patient in whom submucosal invasion was less than 500 microm or tumour was less than 15 mm in diameter developed lymph node metastases. Fewer patients had lymphatic permeation (37/89) and venous involvement (21/89) in the group without lymph node metastases.nnnCONCLUSIONnThese data seem to support the hypothesis that early, minimally invasive, gastric cancer measuring < 15 mm in diameter could be treated by endoscopic mucosal or local resection, and gastrectomy with lymphadenectomy might be unnecessary.

Intestinal ischemia resulting from Buerger's disease: Report of a case

A 42-year-old man who had undergone below-the-knee amputations for Buergers disease 9 and 14 years earlier required emergency surgery for intestinal ischemia caused by arterial occlusive lesions in the mesentery. The cecum and proximal part of the ascending colon were resected, and marked hyperemic thickening of the wall and severe fibrous adhesions were found. Postoperative angiography revealed occlusions in the superior mesenteric and right external iliac arteries. The resected specimen showed mucosal necrosis of the cecum and circular ulcers at Bauhins valve and at the ascending colon. Microscopically, small mesenteric vessels were occluded by organized and recanalized thrombi with preserved vascular architecture. The patient has remained free of any further intestinal symptoms for 1 year following his discharge from hospital.

Differential effect of host microenvironment and systemic humoral factors on the implantation and the growth rate of metastatic tumor in parabiotic mice constructed between young and old mice

B16 melanoma cells were injected into the tail vein of young mice, old mice and parabiotic mice constructed between young and old mice, and the number and shape of pulmonary metastases were compared among three experimental groups. In unpaired mice, the number of metastatic colonies in the lungs was 10-fold larger in young than in old mice. In parabiotic mice, the number in young mice was almost comparable with that of unpaired young mice, but the number in old mice approached the level of young mice. Metastatic colonies on the pulmonary surface of young mice were mostly nodular in shape, while those of old mice were flat in shape. The shape of colonies reflecting the tumor growth rate did not change in parabiotic old mice in spite of an increase in number. In young parabiotic mice, the large and intermediate colonies decreased with a concomitant increase of small ones as compared with unpaired young mice. These results suggest that the implantation of metastatic colonies in the lung is mainly dependent on systemic humoral factors and their growth is mainly dependent on the host local factors in the microenvironment, and distinct age changes of both factors greatly influence the metastatic mode of tumors, respectively.

Chronological Changes in Bone Mineral Content Following Gastrectomy

Recent advances in the modalities of quantitatively assessing bone mineral content have resulted in an increasing awareness of metabolic bone disease as a late complication following gastrectomy. In this study, 98 postgastrectomy patients were examined by quantitative computed tomography (QCT). The bone mineral density index (BMDI), defined as 100×(measured bone mineral density divided by that of age-and sex-matched controls), was used to evaluate the actual effect of gastrectomy on bone disorders. The BMDI values following gastrectomy were 80.4±27.3, with no significant difference between men and women, or between total and distal gastrectomy. Moreover, no significant differences were observed between the BMDI values within 6 months, being 92.6±37.3, and those 6 months to 1 year post gastrectomy, being 79.6±31.2; however, a significant and sharp decrease to 70.5±36.0 was evident after 1–2 years. The regression coefficient of the BMDI measured within 2 years postoperatively was lower than that measured after 2 years. These findings suggest that the influence of gastrectomy on bone metabolism is induced within 2 years, after which the bone mineral content decreases in accordance with physiological nature. Thus, we conclude that the treatment for bone disease resulting from gastrectomy would only be effective if initiated within a short period after surgery.

Comparison by carcinoembryonic antigen doubling time of hepatic injection and infusion for unresectable hepatic metastasis from colorectal cancer

This study explored the efficacy of hepatic arterial therapy, comparing both injection and infusion of 5-fluorouracil (5-FU) in prolonging the survival of 92 patients with recurrent unresectable hepatic metastasis from colorectal cancer. With respect to pretreatment carcinoembryonic antigen doubling time (CEA-DT), 56 patients were treated with intra-arterial injection, and 36 with intra-arterial infusion. In 21 patients with a CEA-DT of less than 40 days, the cumulative survival of patients treated with arterial injection was significantly longer than that of patients treated with arterial infusion. In 45 patients with a CEA-DT of 40-80 days, the survival curves of patients did not differ from each other. Of the remaining 26 patients with a CEA-DT of more than 80 days, those treated using arterial infusion had an excellent prognosis, in contrast to those treated using arterial injection, with statistical significance. CEA-DT may be useful when choosing a chemotherapy regimen, and may help to accurately establish the prognosis of patients with unresectable hepatic metastasis from colorectal cancer.

Effect of Intra-Arterial Injection of Mitoxantrone-Lipiodol Emulsion on Hepatocellular Carcinoma

The effect of intra-arterial injection of mitoxantrone emulsified with ethiodized oil was investigated in 24 patients with hepatocellular carcinoma. After treatment, 6 of the patients underwent hepatectomy. In 18 unresected cases, there were 8 (44%) partial responses, which had continued 2 to 10 months (mean, 7.4 months). In the remaining 6 resected cases, the necrotic areas in the main nodules accounted for 65% (mean, 85%) of the nodule, with complete necrosis in three cases. The results in this preliminary study are encouraging to further study.