Masaharu Tatsuta

Possible role of Helicobacter pylori infection in early gastric cancer development.

Background. Gastric cancer is the most frequently diagnosed malignancy in Japan. The possible relationship between Helicobacter pylori infection and gastric cancer in Japan was evaluated.

Treatment of hepatocellular carcinoma by transcatheter arterial embolization combined with intraarterial infusion of a mixture of cisplatin and ethiodized oil

The therapeutic effectiveness of transcatheter arterial embolization (TAE) with intraarterial infusion of cisplatin/ethiodized oil mixture in treatment of resectable and unresectable hepatocellular carcinoma was compared with TAE with intraarterial infusion of doxorubicin mixed with and without ethiodized oil. The series included 97 patients with unresectable hepatocellular carcinoma and 40 patients with resectable hepatocellular carcinoma. With TAE using doxorubicin infusion, a partial response of the tumor was seen in only 11%, and the 2-yr survival was calculated to be only 5%. Histologic examination of the specimens obtained by hepatectomy also showed that this treatment was relatively ineffective in daughter tumor and portal tumor thrombi. In contrast, TAE with infusion of cisplatin/ethiodized oil mixture significantly increased the rate of partial response (38%), and significantly prolonged the 2-yr survival (45%). Histologically this treatment gave severe necrosis in daughter tumors (69%) and tumor thrombi (78%) as well as main tumor (75%). This treatment was significantly better than TAE with doxorubicin and ethiodized oil infusion in terms of the tumor regression and histologic responses of main tumor and portal vein tumor thrombi, but not in terms of the 2-yr survival. However, 2 patients (8%) died within 4 wk of the latter treatment, whereas no deaths were reported after the former treatment. Therefore, TAE combined with intraarterial infusion of cisplatin/ethiodized oil mixture may be a safe and useful treatment modality for hepatocellular carcinoma.

Effect of a proton pump inhibitor or an H2-receptor antagonist on prevention of bleeding from ulcer after endoscopic submucosal dissection of early gastric cancer : A prospective randomized controlled trial

OBJECTIVES:With conventional methods of endoscopic mucosal resection for early gastric cancer (EGC), proton pump inhibitors (PPIs) and H2-receptor antagonists (H2RAs) have a similar effect on preventing bleeding from artificial ulcers. An objective of this study is to investigate whether a stronger acid suppressant (i.e., PPI) more effectively prevents bleeding after the recent advanced technique of endoscopic submucosal dissection (ESD) for EGC.METHODS:This was a prospective randomized controlled trial performed in a referral cancer center. A total of 143 patients with EGC who underwent ESD were randomly assigned to the treatment groups. They received either rabeprazole 20 mg (PPI group) or cimetidine 800 mg (H2RA group) on the day before ESD and continued for 8 wk. The primary end point was the incidence of bleeding that was defined as hematemesis or melena that required endoscopic hemostasis and decreased the hemoglobin count by more than 2 g/dL.RESULTS:In baseline data, the endoscopists who performed the ESD were significantly different between the groups. Finally, 66 of 73 patients in the PPI group and 64 of 70 in the H2RA group were analyzed. Bleeding occurred in four patients in the PPI group and 11 in the H2RA group (P = 0.057). Multivariate analysis revealed that treatment with the PPI significantly reduced the risk of bleeding: adjusted hazard ratio 0.47, 95% confidence interval 0.22–0.92, P = 0.028. One delayed perforation was experienced in the H2RA group.CONCLUSIONS:PPI therapy more effectively prevented delayed bleeding from the ulcer created after ESD than did H2RA treatment.

Longterm outcomes after endoscopic mucosal resection for early gastric cancer

BackgroundDespite the widespread use of endoscopic mucosal resection (EMR) in patients with early gastric cancer (EGC), its longterm outcomes have not been fully evaluated. Our aim was to evaluate longterm survival after complete EMR for EGC.MethodsFrom patients who underwent EMR between 1978 and 1996 at our center, we enrolled 131 patients with differentiated mucosal EGCs less than 2 cm (without ulcerative change) that had been completely removed by EMR. The vital status of the patients at the end of December 1998 was confirmed by the hospital cancer registry, which is linked to the Osaka Cancer Registry.ResultsA total of 124 patients (95%) were completely followed-up. Two patients (1.5%) died of gastric cancer and 26 died of other causes during the mean observation period of 58 months. The overall 5- and 10-year survival rates were 84% and 64%, respectively. The disease-specific 5- and 10-year survival rates were 99% and 99%.ConclusionEn bloc EMR ensured an excellent prognosis, and should be the first choice of treatment in patients with small differentiated mucosal EGC. Careful histological examination and longterm endoscopic surveillance are important.

Inhibition of angiogenesis as a mechanism for inhibition by Lα-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 of colon carcinogenesis induced by azoxymethane in Wistar rats

The effects of 1α‐hydroxyvitamin D3[1α(OH)D3] and 1,25‐dihydroxyvitamin D3[1,25(OH)2D3] on the incidence of colon tumors induced by azoxymethane and on the labeling index and angiogenesis of colon tumors were investigated in Wistar rats. Rats received 10 weekly injections of 7.4 mg/kg body weight of azoxymethane and i.p. injections of 1α(OH)D3 and 1,25(OH)2D3 at lower and higher doses every other day for 45 weeks. Prolonged administration of both 1α(OH)D3 and 1,25(OH)2D3 at a higher dose significantly reduced the incidence of colon tumors in week 45. However, administration of 1α(OH)D3 or 1,25(OH)2D3 had little or no effect on the histologic type of colon tumors and cancers. Administration of 1α(OH)D3 and 1,25(OH)2D3 at higher doses significantly decreased the labeling index, the immuno‐histochemical staining for vascular endothelial growth factor and microvessel counts in colon tumors. Our findings suggest that both 1α(OH)D3 and 1,25(OH)2D3 inhibit development of colon tumors. A possible mechanism of inhibition of colon carcinogenesis by 1α(OH)D3 and 1,25(OH)2D3 is the inhibition of angiogenesis as well as an anti‐proliferative effect. Int. J. Cancer 81:730–733, 1999.

Cytologic examination of pancreatic juice for differential diagnosis of benign and malignant mucin producing tumors of the pancreas

Background. A new clinical type of pancreatic tumor, the mucin‐producing tumor, has been recognized recently. However, it is not always easy to distinguish benign from malignant tumors preoperatively. In this study, three different methods of differentiating mucin‐producing tumors of the pancreas were compared.

Endoscopic submucosal dissection for early gastric cancer performed by supervised residents: assessment of feasibility and learning curve *

BACKGROUND AND AIM Endoscopic submucosal dissection (ESD) is feasible as a treatment for early gastric cancer (EGC) when it is performed by an experienced endoscopist. We investigated whether it was feasible for novice endoscopists to perform ESD for EGC, and how difficult it was to learn the procedure. METHODS This case series study was performed in a cancer referral center. Three resident endoscopists, who had already learned basic procedures, performed ESD under supervision for 30 consecutive lesions, and their procedures were analyzed. The procedure was divided for assessment into (i) mucosal incision and (ii) submucosal dissection by completion of the circumferential mucosal cut. An insulated-tip knife was used for mucosal incision and submucosal dissection. A total of 90 mucosal EGCs (< or = 2 cm) without ulcers or scars in 87 patients were included. Outcomes were: rates of complete resection, complications, and self-completion; operation time; learning curve; and reasons for change of supervisor as an indicator of difficulty. RESULTS Among the 90 procedures, there was a good overall complete resection rate of 93 %, with an acceptable complication rate of 4.4 %; the complications were delayed hemorrhage in two patients, and perforations in another two patients that were repaired successfully by endoscopic clipping. The self-completion rate and operation time were significantly worse for submucosal dissection than for mucosal incision. Two of the three operators showed a flat learning curve for submucosal dissection. Difficulty with the procedure was related mainly to uncontrollable hemorrhage. CONCLUSIONS With appropriate supervision, gastric ESD by residents is feasible, with equivalent complete resection rates and acceptable complication rates compared with those of experienced endoscopists, although there was difficulty in achieving sufficient self-completion rates in submucosal dissection. Better control of bleeding during submucosal dissection may be a key to improving the procedure.

Endoscopic ultrasonography in diagnosis and staging of pancreatic cancer

The accuracy of endoscopic ultrasonography (EUS) for diagnosis of pancreatic cancers was evaluated in consecutive 232 patients with possible pancreatic cancer, and that for assessment of their locoregional spread was evaluated in 28 patients with pancreatic cancer subjected to pancreatectomy, in comparison with the accuracies of transabdominal ultrasonography (US) and computed tomography (CT). EUS was found to be significantly more accurate than US or CT and was especially useful for detecting small pancreatic cancers of less than 2 cm in diameter. With EUS, pancreatic cancers could be detected as a hypoechoic mass with a relatively unclear margin and irregular internal echoes. EUS was also more sensitive than CT and US for detecting venous and gastric invasions: it was more useful for detecting direct invasion of pancreatic cancers when the tumors were less than 3 cm in diameter. These findings indicate that EUS is an accurate method for diagnosis of pancreatic cancer and assessment of their locoregional spread and is particularly useful for detecting small tumors.

Early depressed adenocarcinomas of the large intestine.

From January 1987 to December 1990, five cases of early depressed cancer of the large intestine were seen. Endo‐scopically, almost all of these tumors were located in the proximal colon and looked like a reddish depression (similar to the sucker of an octopus). Histologically, all of these cancers were well differentiated and tended to reach deeper layers at an early stage. Four (80%) of these cancers were not associated with adenoma and were thought to have arisen de novo. Cancer 1992; 69:2406‐2410.

Diagnosis of pancreatic cancer by detecting telomerase activity in pancreatic juice: comparison with K-ras mutations

OBJECTIVE:Telomerase activity is reported to be specific and very frequent in human malignancy. K-ras mutations are also very frequently detected in pancreatic cancer, but their specificity for pancreatic cancer is controversial. We examined the telomerase activity and K-ras mutations in pancreatic juice from patients with pancreatic disease.METHODS:Pancreatic juice was obtained endoscopically at endoscopic retrograde pancreatography from 10 patients with pancreatic cancer, three with chronic pancreatitis, and three with a normal pancreas. The telomerase activity in pancreatic juice was assayed by telomeric repeat amplification protocol. K-ras mutations in exon 1 codon 12 were examined by the two-step polymerase chain reaction combined with restriction enzyme digestion, followed by single-strand conformation polymorphism analysis and direct sequencing.RESULTS:Telomerase activity of >5.0 was detected in eight of 10 (80%) subjects with pancreatic cancer, but in none with chronic pancreatitis or normal pancreas. K-ras mutations were detected not only in eight of 10 (80%) subjects with pancreatic cancer but also in two of three with chronic pancreatitis and in one of three with a normal pancreas.CONCLUSIONS:It was shown that the detection of telomerase activity in pancreatic juice is a more useful diagnostic tool for pancreatic cancer than that of K-ras mutations.