Nippon Rinsho

[Molecular basis of Hirschsprung disease]

Inoue M. Okada A.
Department of Pediatric Surgery, Osaka University Medical School.
Hirschsprung disease (HSCR) is a congenital malformation caused by the absence of ganglion cells in the myenteric and submucosal plexuses of the gut. Recent studies have shown that mutations in the RET, glial-cell-derived neurotrophic factor (GDNF), endothelin-B receptor (EDNRB), endothelin-3 genes are responsible for the occurrence of aganglionosis. Those genes are involved in the development of neural crest derivatives. The RET gene mutation are found in 50% of familial cases and 15% of sporadic cases. The mutations in other genes were found under 10%. In addition to such a low detection rate of the mutations, incomplete penetrance of the mutation was found in all four genes. Those results support multifactorial or polygenic feature of Hirschsprung disease. The additional candidate genes responsible for this disease will be identified along the signaling pathway through RET and EDNRB.

[Gene delivery using adeno-associated (AAV) vectors]

Year 1998
Funato T.
Department of Clinical & Laboratory Medicine, Tohoku University, School of Medicine.
Gene transfer vectors based on the replication-defective adeno-associated virus (AAV) are emerging as promising vehicles for gene therapeutic approaches for the neurologic disease, cystic fibrosis and cancers. AAV vectors have been used to efficiently transduce genes into cells in vitro and in vivo. However, transduced recombinant AAV vectors are integrated into human chromosomes. Thus we have discussed that the review about the AAV vectors and transduction, and reported the results used AAV vectors for expression of ribozyme.

[Ulcerative colitis--colon delivery of 5-aminosalicylic acid]

Year 1998
Muraoka M. Kimura G. Zhaopeng H. Takada K.
Department of Pharmaceutics and Pharmacokinetics, Kyoto Pharmaceutical University.
Ulcerative colitis, Crohn's disease and hemorrhage colitis are typical example of colon specific diseases. The targeting of the drugs for these colon specific diseases was attempted by a new technology, where ethylcellulose (EC) was used as pharmaceutical material. Especially, pressure-controlled colon delivery capsule (PCDC) made of EC is a unique system. PCDC was prepared by coating the inner surface of gelatin capsule with water-insoluble polymer, EC. By adjusting the coating thickness of EC membrane to be approximately 40 microns, colon delivery of dug were obtained both in beagle dogs and human volunteers. PCDC containing 5-ASA was prepared and was administered orally to beagle dogs. After administration, 5-ASA appeared into the systemic circulation at 3-5 h which corresponds to the colon arrival time confirmed with sulfasalazine.

[Telomerase assay for diagnosis of esophageal cancer]

Year 1998
Koyanagi K. Ozawa S. Ando N. Kitagawa Y. Ueda M. Kitajima M.
Department of Surgery, School of Medicine, Keio University.
Esophageal squamous cell carcinoma is one of the aggressive diseases that has poor outcome. Therefore it is appeared that early diagnosis is very important for improving its outcome. Iodine staining method is useful for detecting the abnormal squamous epithelium and unstaining lesions by iodine contain the early esophageal cancers. Recently, telomerase activity that provides an immortal capacity for the cells has been measured in many tissues. We measured the telomerase activity in the samples of unstaining lesion by iodine using a polymerase chain reaction-based assay and described the relation between telomerase activity and histopathological findings.

[Telomerase activity in esophageal squamous cell carcinoma and in normal esophageal epithelium adjacent to carcinoma]

Year 1998
Ikeguchi M. Kaibara N.
Department of Surgery I, Facalty of Medicine, Tottori University.
Telomerase activity was analyzed in 52 patients with resected esophageal squamous cell carcinoma by telomeric repeat amplification protocol (TRAP) assay. Telomerase activity was detected in 41 out of 52 (79%) carcinomas and detected in 46 out of 52 (89%) normal esophageal epitheliums adjacent to the carcinomas. In carcinoma, the telomerase activity was detected more frequently in relatively early stages of carcinoma (in 8 of 9 patients with stage 0, in 3 of 3 patients with stage I, and in 4 of 4 patients with stage II). However, the telomerase activity was detected in only 8 of 12 patients with stage III and in 16 of 21 patients with stage IV. Thus, the percentage of patients who had tumors without telomerase activity increased in more advanced stages. These results indicate that telomerase activity may correlate with carcinogenasis of esophageal cancer, however, it may not correlate with progression of esophageal squamous cell carcinoma.

[Telomerase activity in esophageal carcinoma and lesions unstained with Lugols solution]

Year 1998
Yoneyama K. Aoyama N. Koizumi H. Tamai S.
Dept. of 1st Surg. Kanagawa Cancer Center, Kanagawa Cancer Center.
Telomerase is a specific enzyme required for the replication of telomeres. Its activity is detected in almost human cancers. We examined in esophageal carcinoma and lesions unstained with Lugol's solution telomerase activity by using telomeric repeat amplification protocol (TRAP) assay. Telomerase activity was detected in all 22 esophageal carcinomas, regardless of histopathological findings. In unstained lesions, telomerase activity was detected in 15 of 22; 10 squamous cell carcinomas, four dysplasia, one regenerative epithelium, no telomerase activity was found in seven; four normal esophageal epithelia, two Barrett's esophagi, one regenerative epithelium. These results suggest that telomerase activity may be a useful molecular marker for the diagnosis of esophageal carcinoma and of the early esophageal carcinoma in area unstained with Lugol's solution.

[Telomere length and telomerase activity in intestinal metaplasia, adenoma and well differentiated adenocarcinoma of the stomach]

Year 1998
Maruyama Y. Hanai H. Kaneko E.
First Department of Medicine, Hamamastu University School of Medicine.
We analyzed telomere length and telomerase activity in intestinal metaplasia (IM), adenoma, and cancer of the stomach and studied the stages at which the cells acquire telomerase activity in carcinogenesis and also the correlation between telomerase activity and telomere length. Telomerase activity was detected in 15%, 45%, 89% of IM, adenomas, and cancers. Telomere lengths shortened as normal mucosa changed into IM and more into adenoma. Gastric cancers showed a broad range of telomeric length. The shortest telomere length was found among gastric adenomas. These results suggest that telomerase is expressed during early phase of gastric carcinogenesis but the activity at that stage is not strong enough to fully restore the reduced telomeric DNA.

[Analysis of expression of human telomerase RNA in gastric precancerous and cancerous lesions by using in situ mRNA hybridization]

Year 1998
Hiyama T. Yokozaki H. Kitadai Y. Tahara H. Yasui W. Tahara E.
First Department of Pathology, Hiroshima University School of Medicine.
We described the localization of human telomerase RNA (hTR) expression in human gastric precancerous and cancerous lesions by using in situ mRNA hybridization. Diffusely high hTR expression was found in all carcinoma and adenoma tissues. Partially high hTR expression was seen in 75% hyperplastic polyps, 47% complete-type intestinal metaplasia and 21% incomplete-type intestinal metaplasia. All chronic gastritis without intestinal metaplasia possessed normal levels of hTR expression. The expression of hTR was heterogeneous and infiltrating lymphoid cells also expressed high levels of hTR expression. Taken together, overexpression of hTR due to stem cell hyperplasia is an early event of carcinogenesis of the stomach.

[Relationship between telomerase activity and clinicopathological findings in gastric cancer]

Year 1998
Ogawa K. Wakasugi S. Katsube T. Hirose K. Kajiwara T.
Dept. of Surgery, Tokyo Women's Med. College, Daini Hosp.
In recent, telomerase has been drawing the attention, because it plays important role in cell immortalization. Since Kim et al exploited TRAP (telomeric repeat amplification protocol) assay which detected telomerase activity efficiently, telomerase activity of various tissues have been detected. In this study, telomerase activity of gastric cancer of resected or biopsy specimen were detected. And we have examined relationship between telomerase activity and clinicopathological factors. In advanced cancer, telomerase activity is negative in 2 cases and positive in 17 cases. In case with lymph node metastasis, negative in 3 cases and positive in 14 cases. In differentiated type, negative 1 cases and positive 20 cases. In noncancerous gastric mucosa, telomerase activity is positive in only 2 cases of 9 cases with intestinal metaplasia. Previous results were same in biopsy specimen. In summary, telomerase activity was detected in 76.7% of gastric cancer and most of advanced cancer or differentiated type. Some intestinal metaplasia cases with telomerase activity suggested precancerous stage.

[Telomerase activity during the cell cycle in gastric cancer cell lines]

Year 1998
Ichikura T. Okusa Y. Mochizuki H.
1st Department of Surgery, National Defense Medical College.
Telomerase, a ribonucleoprotein that adds telomeric repeats onto chromosome ends, is involved in telomere length maintenance and permits unlimited cell proliferation. We examined the possibility that higher telomerase activity is associated with the replicative phase of the cell cycle using gastric cancer cell lines treated with anticancer drugs. Telomerase activity increased at the time point of S-phase accumulation in NUGC-3 cells (5 x 10(5) cells/ml) incubated with CDDP (0.5 microgram/ml), paclitaxel (0.01 microM), or VP-16 (1 microM) and in MKN-28 cells incubated with CDDP. When these cell lines were incubated with 5-fluorouracil (10 microM) or CPT (0.1 microM), the increase of telomerase activity preceded the S-phase accumulation. Our results suggest that telomerase activity be regulated by the cell cycle.

[Diagnostic significance of telomerase activity and telomere length in endoscopic sample of colorectal cancer]

Year 1998
Katayama S. Shiota G. Kawasaki H.
Second Department of Internal Medicine, Tottori University School of Medicine.
Telomeres are located on both ends of individual chromosomes in eukaryotes. It has been reported that telomerase activity and telomere reduction can be detected in most human cancers. We examined telomerase activity and telomere length in colorectal cancer tissues obtained by colonoscopy. Telomerase activity was examined by the TRAP (telomeric repeat amplification protocol) assay and was detected in 21 of 26 (81%) primary colorectal carcinoma tissues. Two of 9 (22%) colorectal polyp were telomerase positive. Telomere length was analyzed by Southern blotting and there was reduction in telomere lengths in 12 of 15 (80%) primary colorectal carcinoma and 3 of 6 colorectal polyp, compared to the corresponding normal colonic mucosa. Therefore, telomerase activity and telomere length may serve as an useful tool for preoperative cancer diagnosis.

[Detection of telomerase activity in intestinal lavage solution from colorectal carcinoma patients]

Year 1998
Ishibashi K. Wakasugi S. Ogawa K. Kato H. Endo S. Yoshimatsu K. Haga S. Hirose K. Kajiwara T.
Dept. of Surgery, Tokyo Women's Medical College, Daini Hospital.
In terms of colorectal carcinoma, the fecal occult blood test is widely used for mass survey, but has many complicated problems to be overcome. Telomerase activity has been reported in a wide range of malignancies. We have examined telomerase activity of intestinal lavage solution collected from 16 colorectal carcinoma patients and from 10 volunteers (control) by the method of telomeric repeat amplification protocol (TRAP) assay. Patients drunk polyethylene glycol-electrolyte lavage solution (PEG-ELS) before examination. Sample solutions were collected by colonoscope at the beginning of colonoscopy. The telomerase activity from colorectal carcinoma patients were positive 9/16 (56.3%) including 2 cases of early stage. In volunteers, were positive 1/10 (10.0%). This method has, therefore, possibility for a new useful method of diagnosis for colorectal carcinoma.

[Telomerase activity in colorectal carcinoma and its relationship to clinicopathological findings]

Year 1998
Iida A. Yamaguchi A. Ohtaki N. Goi T. Hirose K. Nakagawara G.
First Department of Surgery, Fukui Medical University.
Telomerase is thought to be responsible for cell immortality. The telomerase activity in carcinomas has been remarked since 1995. We examined telomerase activity in colorectal carcinoma by TRAP (Telomeric repeat amplification protocol) assay, and investigated its relationship to clinicopathological findings. We could analyse telomerase activities in 33 cases (66%) of 50 colorectal carcinomas, whereas the activity was not found in all 13 cases of noncancerous colorectal mucosa. There was no relation between the telomerase activity and the clinicopathological findings or metastatic status. We confirmed telomerase activities in much of colorectal carcinomas in spite of their progression. The carcinoma cells might be immortal from their early stage of progression by means of telomerase activity.

[Telomerase activity and genomic instability in colorectal cancers]

Year 1998
Unate H. Ikeguchi M. Kaibara N. Oshimura M.
Department of First Surgery, School of Medicine, Tottori University.
In this study, we investigated the correlation between the telomerase activity and the microsatellite instability in colorectal cancers and adenomas. Telomerase activity was detected in 75% of cancers and in 33% of adenomas. Microsatellite instability was detected in 24% of sporadic cancers, in 54% of multiple cancers, and in 22% of adenomas. Telomerase activity and microsatellite instability were independent events in colorectal carcinogenesis. The patients with telomerase activity and microsatellite instability showed poor prognosis. These results indicate that colorectal cancers with both telomerase activity and microsatellite instability may have more malignant potential, and adenomas with both them may be more intensive precursor of colorectal cancers.

[Specific activation of telomerase in pancreatic cancer tissue and preoperative diagnosis of pancreatic cancer by telomerase in pancreatic juice]

Year 1998
Suehara N. Mizumoto K. Niiyama H. Tanaka M.
Department of Surgery 1, Kyushu University Faculty of Medicine.
Telomerase activity was measured in surgically resected tissues in various pancreatic diseases. Relative telomerase activity was expressed as the number of MIA PaCa-2 cells containing an equivalent activity in 1 microgram protein from samples. Telomerase activity in carcinomas was significantly higher than in the other nonmalignant pathologic states. Subsequently, telomerase activity was measured in pancreatic juice from patients with carcinoma, adenoma, and pancreatitis. Telomerase activity in carcinoma samples was significantly higher than that in either pancreatitis or adenoma samples as in tissue samples. High activity of telomerase in pancreatic juice indicates the existence of pancreatic cancer and may serve as a diagnostic tool.

[Telomerase activity in pancreatic juice for the preoperative diagnosis of pancreatic cancer]

Year 1998
Iwao T. Tsuchida A. Hiyama E. Kajiyama G.
First Department of Internal Medicine, Hiroshima University School of Medicine.
Although many diagnostic challenges have been tried in pancreatic cancer, its prognosis still remains poor. One of the reason that it is difficult to diagnose using present diagnostic procedure in early stage of pancreatic cancer. Therefore, we tried new procedure using telomerase activity from pancreatic juice. In this study, telomerase was assayed by use of pancreatic duct cells obtained preoperatively from 32 cases with pancreatic duct abnormalities. Telomerase activity was undetectable in all 17 subjects with benign pancreatic diseases, whereas 13 (87%) of 15 subjects with pancreatic cancer had detectable telomerase activity. Interestingly, we also detected telomerase activity in the case of carcinoma in situ. If future studies confirm, the detection of telomerase activity of pancreatic duct cells may become an useful tool for diagnosis of pancreatic cancer, perhaps at early stages.

[The role of telomerase for pancreatic carcinogenesis in human and hamster]

Year 1998
Tsutsumi M. Tsujiuchi T. Konishi Y.
Department of Oncological Pathology, Cancer Center, Nara Medical University.
Telomerase activity and terminal restriction flagment (TRF) length were investigated in human and hamster pancreatic duct adenocarcinomas. In the hamster primary and transplantable pancreatic carcinomas and cell lines, telomerase activity increased 86 to 215.7 times relative to the levels in normal spleen and pancreas, and reduction of TRF length was observed. In 38 human pancreatic ductal carcinomas, 32 (84%) exhibited increased telomerase activities with no apparent relation to the histological type of tumor, tumor size, regional lymph node involvement and distant metastasis. These results suggest that telomerase play an important role for pancreatic duct carcinogenesis.

[Telomere length and telomerase activity in hepatocellular carcinoma]

Year 1998
Nakashio R. Kitamoto M. Nakanishi T. Takaishi H. Takahashi S. Kajiyama G.
First Department of Internal Medicine, Hiroshima University School of Medicine.
Telomerase activity and terminal restriction fragment (TRF) length were examined in hepatocellular carcinoma (HCC). Telomerase activity was assayed by telomeric repeat amplification protocol (TRAP) connected with an internal telomerase assay standard (ITAS). The incidence of strong telomerase activity (highly variable level compared with the activity of non-cancerous liver tissue) was 79% in well, 84% in moderately, and 100% in poorly differentiated HCC, while 0% in non-cancerous liver tissues. The incidence of TRF length alteration (reduction or elongation) was 53% in HCC. The incidence of TRF alteration was significantly higher in HCC exceeding 3 cm in diameter, moderately or poorly differentiated in histology. Telomerase activity was not associated with TRF length alteration in HCC. In conclusion, strong telomerase activity and TRF length alteration increased with HCC tumor progressions.

[Clinical significance of telomerase activity in precancerous lesion of the liver (adenomatous hyperplasia)]

Year 1998
Nishimoto A. Miura N. Oshimura M.
Department of Molecular and Cell Genetics, School of Life Sciences, Faculty of Medicine, Tottori University.
To understand the role of telomere dynamics in hepatocellular carcinogenesis, we examined the lengths of terminal restriction fragments (TRFs) in hepatocellular carcinoma (HCC) and surrounding tissues with chronic active hepatitis (CAH), liver cirrhosis (LC) and atypical adenomatous hyperplasia (AAH). The peak TRFs in all HCCs were significantly shorter than those of the surrounding tissues (CAH, LC). TRF in AAH was shortened and similar to that of HCC. Telomerase was examined in CAH, LC, AH, and HCC, and detected in high levels almost exclusively in HCCs. Interestingly, the intensity of telomerase activity in the AH was similar to that of HCC. Thus, the progressive shortening of telomere and the activation of telomerase may be a useful marker for the early detection of malignant progression in liver disease.

[Usefulness of telomerase activity in the diagnosis of small hepatocellular carcinoma]

Year 1998
Higashi T. Nouso K. Tsuji T.
First Department of Internal Medicine, Okayama University Medical School.
The diagnosis of small hepatocellular carcinoma (HCC) is sometimes difficult because of the similarity of the histological appearance with adjacent liver tissue. Recent advancement of the quantitative telomerase assay can diagnose small HCC effectively, and the positive rate surpasses those of alpha-fetoprotein and PIVKA-II. The application to a clinical field is, however, limited because the small nodules with the possibility of malignant phenotype tend to be treated easily with ethanol injection therapy without an additional biopsy for this assay only. Further analysis of telomerase related proteins might make it possible to visualize the activity in the tissue sections and expand the usefulness of telomerase as a diagnostic tool in routine clinical use.

[Transarterial enhanced ultrasonography examination of hepatocellular carcinoma using CO2]

Year 1998
Sakaguchi S. Miyajima Y. Tohara K.
Chikushi Hospital, Fukuoka University.
The findings of enhanced ultrasonography under the injection of microbubbles of carbon dioxide into a hepatic artery (CO2-US) were evaluated in the patients with hepatocellular carcinoma (HCC). They were as follows. Most nodules showed early (within 3 seconds) stronger enhancement compared to the surrounding hepatic parenchyma, remaining the enhancing effects more longer than the surround. A few nodule showed isoenhance or nonenhancement. However, metastatic cancer of the liver often showed the early enhancement only at the edge of tumor. In hepatic hemangioma, only the spotty enhancement in the tumor and or the later (later than 4 seconds) enhancement at the edge of tumor was showed. The hyperenhanced mass was detected more often in a larger HCC and revealed to be a relatively poorly differentiated HCC with the capsule formation.

[Diagnosis of small hepatocellular carcinoma by US angiography with intraarterial CO2 microbubbles imaging]

Year 1998
Yamamoto K. Okuda Y.
Division of Ultrasound, Saiseikai Matsusaka General Hospital.
US angiography, enhanced with intraarterial CO2 microbubbles imaging, documented 40 nodules of hepatocellular carcinoma (HCC) lesser than 20 mm in diameter in 34 patients, which were convinced histopathologically. As to the imaging acuity of arterial vascularity in nodules, US angiography was compared with DSA and US color angio. The detection of arterial vascularity was possible in 34 (85.0%) of 40 nodules by US angiography, 26 (65.0%) by DSA, and 28 (70.0 %) by US color angio. US angiography was available for detection of HCC, particularly with small HCC lesser than 20 mm in size.

[The diagnosis of the early stage of hepatocellular carcinoma by US-angiography with intraarterial Albunex (sonicated serum albumin) infusion]

Year 1998
Ono N. Ijuin H. Ono N. Tateishi Y. Ogata R. Kuromatsu R. Itano S. Sata M. Tanikawa K.
Second Department of Internal Medicine, Kurume University School of Medicine.
Contrast-enhanced ultrasonography (arterial infusion) has been clinically established as a qualitative diagnosis imaging tool for hepatocellular carcinoma (HCC). Contrast-enhanced ultrasonography (CEUS) was performed after of Albunex (sonicated serum albumin) or Carbon Dioxide (CO2) microbubble by hand, into the hepatic artery as a diagnostic modality for the early HCC. Here, we discussed the diagnosis of the early HCC by CEUS using Albunex as a contrast medium. Briefly, a diagnosis of the early HCC was made CEUS examination of the hemodynamics of the arteries showed a hypovascular pattern. And tumor size was under 20 mm in diameter, the histopathologic examination was essential to reach a final diagnosis, well-differentiated HCC.

[Contrast enhanced color Doppler sonogram of liver tumors: a color-filled pattern in the late phase]

Year 1998
Tanaka S. Yoshioka F. Kitamra T. Uchimoto R. Niwa K. Miyazawa T.
Osaka Medical Center for Cancer and CVD.
In the present report, a "color-filled pattern", the late phase effect in the intra-venous contrast enhanced color Doppler sonography is introduced, using SH/TA-508 as the contrast agent. This pattern is defined as an image of a tumor area filled with color in contrast to the surrounding liver. After contrast enhancement, the detectability of a "feeding artery" increased. And also "color filled pattern" appeared in 14 of the 21 hepatocellular carcinomas but none of the nine other liver tumors. In conclusion, contrast enhancement increases the detectability of a "feeding artery" and improves the sensitivity for HCC with color Doppler sonography. A "color-filled pattern" is also effective in the diagnosis of HCC because it requires no technical skill and shows high specificity.

[Enhanced color flow findings in small hepatocellular carcinoma]

Year 1998
Maruyama H. Matsutani S. Ebara M. Saisho H.
First Department of Medicine, Chiba University School of Medicine.
Features of enhanced color flow images of small hepatocellular carcinoma (HCC) were studied to elucidate their usefulness in evaluating tumor hemodynamics. Enhanced color Doppler using the contrast agent "SH/TA508" was performed on 16 patients, 13 with HCC, 1 with regenerative nodule, and 2 with hemangiomas, in whom the size of the tumor were smaller than 30 mm. Enhanced color flow appearance was compared with angiographic findings. Significant improvement in the detection of color flow signals was obtained in small HCC using SH/TA508, from 33% in pre-contrast to 92% in post-contrast (p < 0.005). Three patterns of enhanced color flow images, which were related to the angiographic findings, were observed. Enhanced color flow imaging promises to be a useful method for evaluating tumor vascularity noninvasively, and to contribute to the elucidation of the hemodynamics in liver tumor.

[Evaluation of blood flows inside hepatic tumors using color Doppler echography with galactose-based intravenous contrast medium SH/TA 508 administration]

Year 1998
Ishii M. Kawauchi A. Sakamoto M. Sasaki K. Kumano Y. Nishida H. Mukai T. Kusano M.
Second Department of Internal Medicine, Showa University School of Medicine.
The purpose of this study is to evaluate hemodynamic characteristics of various hepatic tumors using color Doppler echography administered galactose-based intravenous contrast medium "SH/TA 508 (Levovist)". Subject were 9 cases of hepatocellular carcinomas, 5 cases of metastatic liver tumors and a case of hemangioma. We evaluated the characteristics of blood flows inside various hepatic tumors, and also evaluated the first pass through the hepatic tumors during administration of Levovist. The strongly pulsatile branched blood flows inside tumor and the slow-increased and plateau patterns were observed in the all cases of hepatocellular carcinomas, the weakly pulsatile blood flows surrounding tumor and the rapid-increased and slow-decreased patterns were observed in the cases of metastatic liver tumors, and the continuous blood streams in the margin of tumor and the slow-increased and slow-decreased pattern were observed in the case of hemangioma. These findings were characteristic in various hepatic tumors, and color Doppler echography enhanced by Levovist was very useful to distinguish hepatic tumors.

[Transcatheter arterial embolization of hepatocellular carcinoma using CO2-US]

Year 1998
Miyajima Y. Sakaguchi S. Tohara K.
Chikushi Hospital, Fukuoka University.
Enhanced ultrasonography under the injection of microbubbles of carbon dioxide into the hepatic artery (CO2-US) contributed to the treatment of hepatocellular carcinoma in the selection of indication of transcatheter arterial embolization (TAE). Judging from the accumulation of the lipiodol after TAE with the combination of lipiodol, TAE was thought to be effective in the tumor which was enhanced by CO2 microbubbles more strongly and the enhancement was prolonged more longer compared to the surrounding parenchyma, even the tumor had no tumor staining on the hepatic angiography. In none of the tumor which had no enhancement, TAE was effective. In most of the tumor with isoenhancement compared with surrounding parenchyma TAE was not effective.

[Usefulness of enhanced US by CO2 microbubbles for segmental-subsegmental TAE for hepatocellular carcinoma]

Year 1998
Ohno K. Fujita M. Nakamura T. Sato O. Maeda T.
Department of Radiology, Kyoto Prefectural University of Medicine.
Enhanced US by intraarterial infusion of CO2 microbubbles is useful for segmental to subsegmental TAE of hepatocellular carcinoma for several reasons. First, we can obtain better recognition of the tumor stain of hepatocellular carcinoma which is even faint on DSA. Secondly, we can recognize the co-relation between tumor stain and its related segment or subsegment well. Therefore, subsegmental or segmental TAE can be performed easily and precisely using enhanced US by CO2 microbubbles. We noted the bigger advantage of enhanced US by CO2 microbubbles especially in the repeated treated cases of TAE for hepatocellular carcinoma.

[The usefulness of percutaneous ethanol injection therapy under guidance with carbon dioxide contrast enhanced ultrasound sonography]

Year 1998
Takeshima K. Kumada T. Kimura T. Nakano S.
Department of Abdominal Ultrasound, Ogaki Municipal Hospital.
We evaluated the usefulness of percutaneous ethanol injection therapy (PEIT) under Carbon dioxide (CO2) contrast enhanced ultrasound sonography (CEUS) guidance during digital subtraction angiography (DSA) in 21 cases of hepatocellular carcinoma (HCC) with 28 nodules that could not be detected by plain (non-contrast enhanced) US (PUS). In all cases of HCC that could not be visualized by PUS, PEIT could be performed successfully under CEUS guidance. Tumor size was below 10 mm in most cases, in 2 cases tumor size was more than 20 mm. Tumor location was roughly divided into 5 areas: just below the diaphragm and it's vicinity, liver surface, edge of the liver, around the portal and hepatic vein, and around the inferior vena cave. The detection rate of the nodules that could not be visualized with PUS was 35.7% for CT and 32.1% for DSA. PEIT was performed 1-9 times for each lesion, 3.32 times on an average. The effectiveness of PEIT was judged by CT. All cases were confirmed as LDA. We concluded that the range of indication of PEIT can be expanded by this method.

[Clinical diagnosis of pancreato-biliary lesions by ultrasound angiography with intra-arterial infusion of carbon dioxide microbubbles]

Year 1998
Okabe Y. Kudo M.
Department of Gastroenterology, Kobe City General Hospital.
Ultrasound angiography (USAG), sonographic imaging of the blood flow with intra-arterial infusion of carbon dioxide (CO2) microbubbles, was applied to pancreato-biliary lesions. Hypervascular pattern was observed in all cases of gallbladder elevated lesions except for debris balls. However, the vascular pattern of CO2 inflow that many arterial vessels were branching off into the lesion was characteristic for gallbladder carcinomas. The hemodynamics of solid tumors of the pancreas with USAG were divided into three patterns. Most of hypovascular nodules were duct cell carcinomas, while inflammatory pancreatic masses always exhibited isovascular except for two cases of hypovascular pattern. Furthermore, islet cell tumors showed hypervascular. In cases of mucin-producing cystic tumors of the pancreas, excrescent nodules or thickened septa within the lesions were identified as hypervascular. Other cystic tumors of the pancreas also presented peculiar hemodynamics. Therefore USAG is potentially useful for detecting various vascular patterns of pancreato-biliary lesions, contributory as a diagnostic tool in this area.

[Clinical assessment of contrast-enhanced ultrasonography for the diagnosis of gall bladder diseases]

Year 1998
Nagakawa T. Koito K. Fujinaga A. Suga T.
Department of Gastroenterology, Sapporo Kohsei General Hospital.
We evaluated the efficacy of contrast-enhanced ultrasonography (CEUS) with intra-arterial injection of CO2 microbubbles in 37 cases of gall bladder diseases. CEUS clearly visualized arterial flow and vascularity in every lesions without debris and gave us the precise information of vascular structure for the differential diagnosis of gall bladder tumors. For example, highly bifurcated tumor vessels and strong enhancement was observed in gall bladder cancer and we could detect relatively strong enhancement along the lumen with lack of enhancement of Rokitansky-Aschoff sinus in localized-type adenomyomatosis. Though CEUS is now an invasive modality, it will enable us to understand the non-invasive modality such as color doppler imaging with intra-venous administration of microbubbles in the future.

[Color Doppler signal enhancement with SH/TH-508 in pancreatic tumors]

Year 1998
Imai H. Horiguchi Y. Kubo H. Suzuki T. Sakamoto K. Uematsu M. Takeuchi F. Nakamura H. Hayashi T. Tokuda A. Asano M. Murai J. Osakabe K. Kushi Y. Nishikawa T. Sugita Y. Soeshima C.
Department of Gastroenterology, Fujita Health University.
In this report, we showed the efficacy of a new contrast agent (SH/TA-508, Schering AG, Germany) for color Doppler imaging of the pancreatic tumors. In pancreatic ductal cancer, no enhancement of the lesion was observed, but vascular invasion by cancer became to be easily evaluated. On the other hand, hypervascular tumors such as islet cell tumor and cystadenocarcinoma, were increased in color Doppler signals of vessels by SH/TA-508. We concluded that SH/TA-508 was useful for evaluating the vascular invasion by pancreatic cancer as well as vascularity of hypervascular mass and solid component of cystic neoplasma.

[Differential diagnosis of pancreatic tumor by contrast enhanced color Doppler ultrasonography]

Year 1998
Miyata T. Tomiyama T. Tano S. Ueno N.
No information.
For evaluating abdominal hemodynamic changes and diagnosing mass lesion, recently color Doppler ultrasonography (CDUS) have been applied. However, there are limitations in visualizing Doppler signals in small vessels with low flow velocity. To overcome these shortcomings, several contrast agents that facilitate evaluation of abdominal hemodynamics have been developed. We underwent Contrast enhanced color Doppler ultrasonography (CECD) with a galactose-based contrast agent in three patients with pancreatic tumor. In the patient with tumor forming pancreatitis, only CECD visualized the color signal in and around the tumor. In the patient with duct cell cancer, CDUS and CECD visualized only the color signal of the splenic artery penetrating the tumor, whereas in the patient with islet cell tumor, CECD visualized numerous color signals in the tumor. CECD appears to be useful in diagnosing pancreatic tumor.