Clinicopathological study of early adenocarcinoma of the gastric cardia: comparison with early adenocarcinoma of the distal stomach and esophagus.

To clarify the clinicopathological characteristics of adenocarcinoma of the gastric cardia (AGC), including its association with Barrett's esophagus and intestinal metaplasia, 49 surgically resected early AGCs (EAGCs) were examined clinicopathologically, histopathologically, histochemically, and immunohistochemically. The clinicopathological characteristics of the patients with EAGC were compared with those of 293 patients with early adenocarcinoma of the distal stomach (EADS) and 7 patients with early adenocarcinoma of the esophagus (EAE). Histochemical staining with paradoxical concanavalin A (ConA) and immunohistochemical staining with monoclonal antibodies 45M1, Ccp58, and 56C6 were performed to investigate the differentiation phenotype of the tumor. ConA and 45M1 were used for markers of the gastric phenotype, and Ccp58 and 56C6 were used for markers of the intestinal phenotype. EAGC was associated with a higher mean age (p < 0.0001), a higher male-to-female ratio (p < 0.05), a higher incidence of elevated-type tumors (p < 0.0001), a higher incidence of differentiated-type tumors (p < 0.0001), and greater depth of invasion (p < 0.05) compared with EADS. EAE was associated with a higher incidence of elevated-type tumors (p < 0.001), a higher incidence of differentiated-type tumors (p < 0.05), and larger tumor size (p < 0.05) compared with EADS. The prevalence of Barrett's esophagus in patients with EAGC was significantly lower than in patients with EAE (10.2%, 5/49 patients vs. 100%, 7/7; p < 0.0001). The prevalence of intestinal (Barrett's) metaplasia in surrounding non-neoplastic mucosa in patients with EAGC was significantly lower than in patients with EADS or EAE (36.7%, 18/49 patients vs. 72.0%, 211/293 and 85.7%, 6/7; p < 0.0001 and p < 0.05, respectively). EAGC was associated with a higher incidence of tumors that reacted positively for gastric phenotype markers alone than EADS (32.7%, 16/49 cases vs. 17.1%, 50/293; p < 0.05) and a lower incidence of tumors that reacted positively for both gastric and intestinal markers than EADS or EAE (40.8%, 20/49 cases vs. 59.7%, 175/293 and 85.7%, 6/7; p < 0.05, respectively). Our findings indicate that AGC forms a specific category different from both adenocarcinoma of the distal stomach and esophagus in terms of association with Barrett's esophagus or intestinal metaplasia, and the differentiation phenotype of the tumor.

Other primary cancers occurring after treatment of superficial oesophageal cancer.

BACKGROUND: Recent advances in endoscopic diagnosis and treatment have led to better prognosis for patients with superficial oesophageal cancer. The incidence of subsequent other primary cancer (SOPC) has become a new problem for patients who survive after treatment of superficial oesophageal cancer. METHODS: Between 1966 and 1998, 368 patients with superficial oesophageal cancer, histologically confirmed as squamous cell carcinoma after resection, were reviewed for the presence of SOPC. RESULTS: Among the 368 patients, 43 developed SOPC. The most frequent sites of SOPC were the stomach (11 patients) and hypopharynx (11). Subsequent cancers of the stomach and hypopharynx developed significantly more frequently in heavy smokers. The 5-year cumulative occurrence rate of subsequent cancers within the fields of endoscopy of the upper gastrointestinal tract (stomach, hypopharynx and residual oesophagus) was 15 per cent. CONCLUSION: Gastric and hypopharyngeal cancers were frequently found after resection of superficial oesophageal cancer. A history of heavy smoking at the time of initial resection may be a risk factor. To make an early diagnosis of subsequent cancers, follow-up observation by upper gastrointestinal endoscopy is important after treatment of oesophageal cancer.

Increased expression of cyclooxygenase-2 in human pancreatic neoplasms and potential for chemoprevention by cyclooxygenase inhibitors.

BACKGROUND: Cyclooxygenase-2 (COX-2) is thought to be linked to carcinogenesis; however, very little is known about its expression in pancreatic neoplasms. The authors studied the expression of COX-2 in human pancreatic neoplasms and investigated the effect of COX inhibitors on the growth of human pancreatic carcinoma cells. METHODS: Expression of COX-2 protein was immunohistochemically examined in 42 human pancreatic duct cell carcinomas (PDCs) and in 29 intraductal papillary mucinous tumors (IPMTs [adenomas, 19; carcinomas, 10]) of the pancreas that were resected surgically at the National Cancer Center Hospital in Tokyo. The growth of four human pancreatic carcinoma cell lines also was evaluated in the presence of COX inhibitors. RESULTS: Marked COX-2 expression was observed in 57% (24 of 42) of PDCs, in 58% (11 of 19) of adenomas, and in 70% (7 of 10) of adenocarcinomas of IPMTs. However, there was no correlation between COX-2 expression and clinicopathologic indices of the patients. All four pancreatic cancer cell lines expressed COX-2 protein weakly or strongly, and the inhibitory effect of aspirin on cell growth was correlated with the expression of COX-2. CONCLUSIONS: COX-2 was expressed in adenomas of IPMTs as well as in carcinomas and might have played a role in the development of pancreatic tumors. In this study, COX inhibitors, as nonsteroidal anti-inflammatory drugs, were shown to be possible preventive agents against pancreatic neoplasms.

[The prognostic factors of pancreatic cancer--adhesion molecule CD44].

The prognosis for pancreatic cancer is extremely poor, because there are usually invasion of surrounding tissues and metastases to lymph nodes, liver or peritoneum at the time of diagnosis. Many studies from the molecular-biological stand point have demonstrated this poor prognosis. However, the mechanisms underlying these invasive and metastatic capabilities have not yet been clarified. We reviewed several reports for prognostic factors of pancreatic cancer in molecular-biological examinations, and introduced our recent study on the adhesion molecule CD44. The CD44 variant 6 (v6) molecule has been noted as a marker for tumor metastasis and prognosis in several tumors. We examined whether or not v6 is a useful marker for evaluating the prognosis of pancreatic cancer patients. In addition, we attempted to assess the clinicopathological implications for pancreatic cancer of the variant 2 (v2) isoform using a recently developed monoclonal antibody against a v2 epitope. The expression of CD44 v6 and v2 was observed only in tumor cells, if at all. The expression of CD44 v6 and v2 was correlated with decreased overall survival. A significant correlation was obtained between CD44 v2 and vessel invasion. These results suggest that CD44 v2 and CD44 v6 may be useful markers of a poor prognosis.

[Percutaneous transcatheter thermotherapy (PTCT): use of hotwire for local tumor control].

We developed a Hotwire for use in percutaneous transcatheter thermotherapy (PTCT) for local tumor control. The Hotwire has a temperature sensor and a heater, and is inserted into the hepatic artery through a Y-connector and an angiocatheter. It can then warm fluid from the Y-connector to 45 degrees C under electorical control PTCT was performed on liver tumors using 4 mg of MMC and 10 mg Epirubicin. The antitumor effects and indications for PTCT were investigated in patients with unresectable liver tumors, including 3 patients who had hepatocellular carcinoma (HCC) with intraportal invasion and collateral vessels, one patient with liver metastasis of rectal cancer, and two gastric cancer patients. In all patients, tumor marker levels decreased (PIVKA-II; 8.5-->0.9, 2.9-->0.9, AFP; 1154-->753, CEA; 300-->226, TPA; 6319-->4227, 3312-->943), and CRP levels were markedly elevated with tumor fever. The only adverse reaction to PTCT was nausea and vomiting in one female patient. We repeated PTCT 6 times for giant HCC, and performance status was improved (2-->0). In conclusion, PTCT using the Hotwire is useful for treating hypervascular tumors limited to the liver, especially HCC with intraportal invasion and collateral vessels.

Changes in DNA copy number in primary gastric carcinomas by comparative genomic hybridization.

We examined 33 primary gastric carcinomas using comparative genomic hybridization to detect changes in the DNA copy number and the chromosomal location of these changes. Ninety-four percent (31 of 33) showed 1 or more DNA copy number changes, such as increases at 2p23-p25 (observed in 21% of the total cases), 3q26.3-q27 (24%), 7p15 (24%), 9p22-pter (18%), and 13q22-q34 (21%) and decreases at 1p34.2-p36.2 (18%) and Y (52%). Histological examination indicated that increases at 3q26.1-q26.3 and 7p15 and decreases at 1p36.1-p36. 2 and Y were commonly observed in both differentiated and undifferentiated types. Increases at 3q27, 6q23-q25, and 7cen-p14 and decreases at 1p34.2-p35 and 17p12 were predominantly observed in the differentiated type, and increases at 2p23-pter, 9p22-pter, and 13q31-qter and a decrease at 6p21.3 were predominantly observed in the undifferentiated type. In addition, clinical staging of tumors showed that increases at 2p23-p25, 7p14-p21, 7q31-q32, and 9p22-pter and a decrease at Y were observed in early-stage tumors, whereas increases at 9q32-q33 and 15q26 were observed only in late-stage tumors. Many of the abnormalities detected in this study were not previously reported in gastric carcinomas. Our comparative genomic hybridization results indicate the presence of genetic alterations that may play some important role in the development and progression of gastric carcinomas.