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Oncol Rep

Evaluation of the 5 spliced form of human cathepsin B mRNA in colorectal mucosa and tumors.

Hizel C. Ferrara M. Cure H. Pezet D. Dechelotte P. Chipponi J. Rio P. Bignon YJ. Bernard-Gallon D.
Laboratoire d'Oncologie Moleculaire, INSERM CRI 9402, Centre Jean Perrin, 58 rue Montalembert, B.P. 392, 63011 Clermont-Ferrand Cedex 1, France.
To evaluate the 5' spliced form of human cathepsin B mRNA in colorectal mucosa and tumors, we have determined the ratio of the spliced form for the exon 2/the complete form of cathepsin B mRNAs obtained by RT-PCR. Such ratio is significantly higher in colorectal tumors than in colorectal mucosa (p < 0.05, Kruskal-Wallis test) or in skeletal muscle (p < 0.05). Moreover, 2-fold more complete form than the spliced mRNA was found in the tumors than in the colorectal mucosa. Our data indicate that the alternative splicing of human cathepsin B mRNA in the 5'UTR may be considered as an indicator of the cellular transformation, in colorectal cancer.

Fas antigen expression in hepatocellular carcinoma tissues.

Ito Y. Takeda T. Umeshita K. Sakon M. Wakasa K. Matsuura N. Monden M.
Department of Surgery II, Osaka University Medical School, Japan.
Fas antigen belongs to the tumor necrosis factor receptor family and is known to induce apoptosis. This protein is abundantly expressed in hepatocytes, especially in acute and chronic hepatitis. To elucidate the clinical significance of Fas in hepatocellular carcinoma (HCC), we investigated its expression in 50 HCC having various characteristics. Fas was comprehensively expressed in non-cancerous hepatocytes as well as bile ducts. It was moderately expressed in histiocytes in the stroma rather than in infiltrating lymphocytes. In HCC, Fas expression was significantly reduced when there was poor differentiation (p

Enhancement of CDDP cytotoxicity by caffeine is characterized by apoptotic cell death.

Takahashi M. Yamamoto Y. Hatori S. Shiozawa M. Suzuki M. Rino Y. Amano T. Imada T.
First Department of Surgery, Yokohama City University, School of Medicine, Japan.
Through the use of STKM-1 human stomach cancer cells, we investigated the enhancement of the anti-tumor effect and the apoptosis induction of the CDDP and caffeine combination. Even when the concentration of CDDP was low, CDDP significantly decreased the proliferation of STKM-1 human stomach cancer cells, thus confirming the synergistic effect of the CDDP and caffeine group. The apoptotic labeling index of the CDDP plus caffeine combination was significantly higher than that of the CDDP group. In conclusion, caffeine enhanced the effect of CDDP by not only inhibiting DNA repairs but also inducing apoptosis.

Preoperative estimation of neural invasion in rectal carcinoma.

Matsushima T. Mori M. Kido A. Adachi Y. Sugimachi K.
The Second Department of Surgery, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
To reduce postoperative local recurrence in patients who undergo a nerve preserving operation for rectal carcinoma, preoperative estimation of neural invasion would be desirable. For this purpose we clarified the characteristics of rectal carcinomas with neural invasion and then evaluated the usefulness of matrix metalloproteinase 7 (MMP7) gene as an indicator for neural invasion. The study included 128 patients with primary rectal carcinoma. The histologic examination plus immunohistochemical study for S-100 protein was performed. A reverse transcription-polymerase chain reaction (RT-PCR) study for MMP7 using preoperatively obtained biopsy specimens was also performed in 32 patients. Neural invasion was recognized in 38 (29.7%) of 128 tumors. The tumors with neural invasion were characterized by infiltrative growth pattern, frequent lymphatic and venous permeation, frequent lymph node metastasis, and advanced stage of disease. The cases with neural invasion also showed a higher recurrent rate and worse prognosis. An RT-PCR study demonstrated that a significantly higher expression of MMP7 mRNA was recognized in neural invasion positive cases than in negative ones (p

Absence of mutatins in the analysis of coding sequences of the entire transforming growth factor beta type II receptor gene in sporadic humangastric cancer using genomic DNA and intron primers.

Takenoshita S. Mogi A. Osawa H. Sunaga H. Kakegawa H. Tani M. Morinaga N. Kato R. Hagiwara K. Nagamachi Y.
First Department of Surgery, Gunma University School of Medicine, 3-39-22, Showamachi, Maebashi, Gunma, 371, Japan.
Mutations in the transforming growth factor beta type II receptor (TGFbetaRII) gene have been detected in several human cancers that represent the phenotype of genomic instability. To establish a basis for diagnosis of cancer patients, we previously determined the exon-intron organization of the TGFbetaRII gene. The results indicated that TGFbetaRII protein is encoded by 567 codons in 7 exons. In this study, we further determined the nucleotide sequences surrounding these 7 exons and designed 8 sets of intron-based primers to examine the entire coding region of the TGFbetaRII gene. By using these primers, we screened for mutations of the TGFbetaRII gene in DNAs of 32 sporadic gastric cancer patients in whom one case showed MI+ (3.1%) at two loci. We found no mutations, and these data support other recent evidence that TGFbetaRII mutations rarely occur except in colon and gastric tumors with MI.

Evaluation of transverse colon interposition following total gastrectomy in patients with gastric carcinoma.

Hosouchi Y. Nagamachi Y. Hara T.
First Department of Surgery, Gunma University School of Medicine, Gunma 371, Japan.
In order to improve the quality of life of patients who received total gastrectomy for treatment of gastric carcinoma, transverse colon interposition (TCI) was performed on 133 patients since June, 1986. To evaluate TCI, post-operative follow-up studies were conducted. Group I patients received TCI (N=40). Group II patients received Roux en Y anastomosis (R-Y anastomosis) (N=20). These groups were compared in a five-year post-operative study. Alkaline reflux esophagitis was significantly lower among patients who received TCI compared to patients who received R-Y anastomosis (p

Analysis of p53 expression in precancerous and malignant gastric mucosa.

Romiti A. Moretti A. Vecchione A. Muraro R. Feudi ML. Rinaldi V. Mancini R. Valli C. Mozzicafreddo A. Frati L. Tomao S.
Istituto Nazionale per la Ricerca sul Cancro di Genova Sezione di Biotecnologie, Roma, 00171, Italy.
P53 overexpression, detected by immunohistochemical analysis, has been reported in about 50% of gastric cancers whereas scarce data are available on the p53 oncoprotein in precancerous gastric lesions. This study focused on the p53 expression in gastric cancerous and precancerous lesions. One hundred gastric specimens obtained during endoscopy were analyzed: 14 cases of normal gastric mucosa, 53 of chronic gastritis with intestinal metaplasia and/or dysplasia and 33 gastric tumors. An immunoperoxidase technique and monoclonal anti-p53 antibodies were employed. Eleven out of 31 gastric carcinomas overexpressed p53. No correlation was observed between p53-positivity and histological type and grade of tumors. All precancerous lesions were p53-negative. Our results suggest that p53 overexpression is a relatively late event in gastric carcinogenesis.

Second primary extracolonic cancers in Japanese hereditary nonpolyposis colorectal cancer.

Tomoda H. Baba H. Taketomi A. Kohnoe S. Seo Y. Saito T.
Department of Gastroenterological Surgery, National Kyushu Cancer Center, Fukuoka, 815, Japan.
We examined the occurrence of second primary extracolonic cancers in 1,170 patients with nonpolyposis colorectal cancer who underwent a resection between 1972 and 1994. Such cancers occurred more often in cases with hereditary nonpolyposis colorectal cancer (HNPCC) than in those without (11.1% vs. 3.6%, P=0.0286). Five HNPCC cases developed 6 cancers in the stomach, endometrium, ovary, and ureter. The mean interval between the first and second operation was 66 months (range: 18-153). These findings thus indicate the importance of targetted surveillance for any second primary cancers in the upper gastrointestinal, female genital, or upper urologic tract, especially in HNPCC patients.

Multiple primary colorectal and gastric carcinoma in Japan.

Tomoda H. Taketomi A. Baba H. Kohnoe S. Seo Y. Saito T.
Department of Gastroenterological Surgery, National Kyushu Cancer Center, Fukuoka, 815, Japan.
We investigated the occurrence of multiple primary colorectal and gastric cancer (MPCGC) in 1277 colorectal cancer patients between 1972 and 1996. MPCGC was found in 65 (5.1%). In the 28 synchronous cases, gastric or colorectal cancer was accidentally detected by pre-, intra-, or postoperative examinations. In 23 of the 37 metachronous cases, colorectal cancer developed on average 83 months after the operation for gastric cancer. In the other 14 cases, gastric cancer developed on average 70 months after the operation for colorectal cancer. Therefore, careful pre-, intra-, or postoperative examinations are strongly called for in order to not overlook the presence of colorectal or gastric lesions in MPCGC cases.

High mortality rates from liver cancer in the urban area of Campania Region: prevalence of hepatitis and sociodemographic factors.

Montella M. Bidoli E. De Marco MR. Iannuzzo M. Fusco M. Palombino R. Franceschi S. Monfardini S.
Servizio di Epidemiologia, Istituto Nazionale Tumori Fondazione G. Pascale, Cappella Cangiani, Naples, 80131, Italy.
The incidence of liver cancer appears lower in Europe and the USA and it is often looked upon as a problem in developing countries. Liver cancer has two main risk factors: the abuse of alcohol and the elevated prevalence of hepatitis B and C viruses. In Italy the first one is mainly present in the North and the second one in Southern less developed areas. Our study evaluates the relationship between living in urban and suburban zones in South of Italy in conditions of overcrowding, poor health services and high incidence of hepatitis and liver cancer.

Amplification and overexpression of cyclin D1 in aggressive human esophageal cancer.

Inomata M. Uchino S. Tanimura H. Shiraishi N. Adachi Y. Kitano S.
First Department of Surgery, Oita Medical University, Hasama-machi, Oita 879-55, Japan.
Cyclin D1 is a cell-cycle regulator essential for G1 phase progression and a candidate proto-oncogene implicated in pathogenesis of several human tumor types including esophageal cancers. Association between cyclin D1 gene amplification and clinical outcome was examined using southern blotting in 45 patients with primary esophageal cancer. In cases showing gene amplification, expression levels of mRNA and gene product were further examined by northern blotting, western blotting and immunohistochemical analyses. Amplification of cyclin D1 gene was found in 14 of 45 patients (31. 1%). There was no association between gene amplification and clinicopathological parameters but the frequency of hematogenous recurrence in cases with gene amplification was significantly higher than that in cases without amplification in 30 patients undergoing curative surgery (70.0% vs 25.0%, p

The antiproliferative effect of HGF on hepatoma cells involves induction of apoptosis with increase in intracellular polyamine concentration levels.

Yanagawa K. Yamashita T. Yada K. Ohira M. Ishikawa T. Yano Y. Otani S. Sowa M.
First Department of Surgery, Osaka City University, Medical School, 1-5-7 Asahimachi, Abenoku, Osaka 545, Japan.
Hepatocyte growth factor (HGF) induced apoptosis and decreased the DNA synthesis in Hep G2 cells. In the HGF group interleukin-1 converting enzyme, ornithine decarboxylase (ODC) activity and intracellular polyamine concentrations were increased compared to those of the control group. Administration of the ODC inhibitor decreased polyamine concentration, and inhibited apoptotic changes in the cells. These changes were reversed by exogenous addition of polyamine. These findings suggest that one of the mechanisms by which HGF exerts its antiproliferative effect is induction of apoptosis and that increase in intracellular polyamine concentration may be one of the triggers of cell death.

Cell-proliferative activity and its relationship to the histologic type of early gastric cancer.

Wang Z. Ikeguchi M. Maeta M. Kaibara N.
Department of Surgery I, Faculty of Medicine, Tottori University, Nishimachi 36-1, Yonago 683, Japan.
To evaluate the biological characteristics of gastric carcinoma and of the normal gastric mucosa from which carcinoma seems to develop, we analyzed the DNA content and proliferative activity of cells in 154 patients with primary mucosal gastric cancer and 40 patients with gastric ulcer by flow cytometric analysis. A total of 154 samples from mucosal gastric carcinomas, 154 samples from normal gastric mucosa adjacent to carcinomas and 40 samples from normal gastric mucosa adjacent to gastric ulcers were subjected to analysis. The incidence of DNA aneuploidy of differentiated carcinoma cells (34.3%) was significantly higher than that of undifferentiated carcinoma cells (14.5%, P=0.014). Among the cancers with diploid DNA, the mean value of the proportion of cells in the S phase of the cell cycle in differentiated carcinomas was 6.64% and it was significantly higher than that in undifferentiated carcinomas (5.53%, P=0.01). The mean values for the S and G2 + M phases for cells in the normal gastric mucosa from sites adjacent to the differentiated carcinomas were 5.29% and 1.81%. These values were higher than those for cells in normal gastric mucosa from sites adjacent to undifferentiated carcinomas (4.89% and 1.40%, respectively) and than those for cells in normal mucosa from sites adjacent to gastric ulcers (4.48% and 1.68%, respectively). During the early phase of gastric cancer, differentiated carcinoma seems to develop from gastric mucosa where cells have high proliferative activity. Reflecting this biological characteristic, the cells of differentiated carcinomas also have high proliferative activity.

Combination of calcitonin and pamidronate for emergency treatment of malignant hypercalcemia.

Sekine M. Takami H.
First Department of Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173, Japan.
To combine the rapid hypocalcemic effects of calcitonin with the delayed effects of pamidronate, a combination of a single dose of pamidronate and serial doses of eel calcitonin was administered to five patients with malignant hypercalcemia for 2 to 5 days. The serum calcium levels of all five patients fell within 24 h after administration of pamidronate and the first dose of calcitonin and decreased to normal within 4 days. The mean level of corrected serum calcium fell from 15.3 mg/dl (range 14.1-16.4 ) to 9.2 mg/dl (8.9-9. 6) at the nadir. No toxicity or side effects were found. The results of this study demonstrate the value of combining the rapidly acting antiresorptive and renal calciuretic effects of calcitonin with the slower, but more potent effects of pamidronate. The combination of calcitonin and pamidronate allowed rapid, long-term control of hypercalcemia and it is regarded as the first choice of treatment in severe hypercalcemia.

The incidence of hepatocellular carcinoma in patients with chronic hepatitis C after interferon treatment.

Miyajima I. Sata M. Kumashiro R. Uchimura Y. Ide T. Suzuki H. Tanikawa K.
Second Department of Medicine, Kurume University School of Medicine, 830, Japan.
To determine whether serum hepatitis C virus (HCV) RNA disappearance after interferon (IFN) treatment prevents development of hepatocellular carcinoma (HCC), we evaluated retrospectively the incidence of HCC in patients with chronic hepatitis C. A total of 213 patients were monitored for more than 6 months after completion of IFN treatment. Sixty-three of the 213 patients (29.6%) achieved a complete response (CR) to treatment and 150 (70.4%) had no response (NR). HCC developed in 12 (5.6%), all of whom were NR. Logistic analysis showed age, alpha -fetoprotein, and staging of histological finding before IFN treatment were independent factors to development of HCC. The fact that there was no HCC development from CR provides a basis for IFN treatment in chronic HCV infection.

Long-term evaluation of interferon therapy in hepatitis C virus-associated cirrhosis: does IFN prevent development of hepatocellular carcinoma?

Tanaka K. Sata M. Uchimura Y. Suzuki H. Tanikawa K.
Second Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume-shi, Fukuoka 830, Japan.
During the course of long-term follow-up, we examined the efficacy of interferon (IFN) in the improvement of liver function and prevention of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV) associated cirrhosis patients. Fifty-five cirrhotic patients, in whom HCC nodules in the liver were not detected by ultrasonography (US) or computed tomography (CT), received 3 or 6 million units of human lymphoblastoid IFN daily for two weeks and 3 times a week for 22 weeks. Complete response (CR) was defined as normalization of serum alanine aminotransferase (ALT) together with negative HCV RNA at 6 months after IFN therapy completion. Any other pattern of response was defined as non-response (NR). After IFN therapy the patients were followed up every 1-3 months for at least 1 year (average follow-up period, about 40 months) with serological tests and US or CT. In the 8 CR patients, the serum ALT levels remained normal and HCV RNA remained negative. Platelet count, white blood cell count, serum albumin and zinc turbidity test have recovered to the normal range at final follow-up. Ten of the 47 patients with NR have developed HCC, whereas no patients with CR has developed HCC during follow-up. We conclude that IFN improves the liver function and may prevent the development of HCC even in cirrhotic patients who show CR to IFN therapy.

Effects of PALA on the pharmacokinetics of 5-fluorouracil.

Nassim MA. Rouini MR. Cripps MC. Shirazi FH. Veerasinghan S. Molepo JM. Obrocea M. Redmond D. Bates S. Fry D. Stewart DJ. Goel R.
Ottawa Regional Cancer Centre, 190 Melrose Avenue, Ottawa, Ontario K1Y 4K7, Canada.
N-(phosphonacetyl)-L-aspartate (PALA) modulates the activity of 5-fluorouracil (5-FU) by inhibiting pyrimidine biosynthesis. A cross-over study was conducted to determine whether PALA affects the pharmacokinetic parameters of 5-FU in patients given 5-FU/folinic acid (FA). Six patients (3 males, 3 females) aged 63 4.3 (mean SD) years (body surface area of 1.84 18 m2) with metastatic colorectal carcinoma were given two courses of treatment. The treatment consisted of 250 mg/m2 of PALA on day 1 followed by 20 mg/m2 FA and 400 mg/m2 5-FU (5 min i.v. bolus injection) on days 2-5 in one cycle of treatment (PALA+). In another treatment cycle, these doses of 5-FU and FA were given for all 5 days without PALA (PALA-). The two courses were given four weeks apart. It was determined by random selection whether the course with PALA was given before or after the course without PALA. Blood samples were collected over a period of three hours, starting from the beginning of 5-FU infusion on days 2 and 5 of both courses. Plasma concentrations of 5-FU were determined by an HPLC technique. Pharmacokinetic parameters were calculated using a non-compartmental model. While there were no significant differences between pharmacokinetic parameters in the PALA+ vs PALA- courses, there was a trend towards a decreasing area under the curve (AUC) and increasing clearance (Cl) in PALA+ courses of treatment.

Oligosaccharide Le(a)-Le(x): a cell surface marker for carcinomas derived from embryonic endoderm.

Stranahan PL. LaRoe J. McCombs R. Rahim I. Kuhn CW. Pettijohn DE.
University of Colorado Cancer Center, Department of Biochemistry, Biophysics and Genetics, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
An immunohistochemical evaluation of Le(a)-Le(x) expression by adenocarcinomas of the biliary tree, pancreas, colon and stomach was undertaken as examples of epithelial tumors derived from embryonic endoderm. This complements previous studies showing that Lea-Lex was present on the cell surface of non-small cell lung carcinomas, some non-lung carcinomas, and is a prognostic marker for squamous cell lung carcinomas. All of the tumor specimen evaluated were positive and no expression of Le(a)-Le(x) was detected in derivatives of neural, connective or muscle tissues. These findings indicate that it could be informative to examine the biological significance of Le(a)-Le(x) not only in carcinogenesis but during embryogenesis, as well.

Distinctive karyotypes and growth patterns in nude mice reveal cross-contamination in an established human cancer cell line.

Price JE. Wolf JK. Pathak S.
Department of Cell Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
A human cancer cell line was found to be heterogeneous for expression of the epidermal growth factor receptor (EGFR). Clones and variants of this cell line were separated on the basis of EGFR expression level, and those expressing high EGFR had different growth characteristics, in vitro and in vivo, than variants expressing low levels of EGFR. Karyotype analysis revealed that the heterogeneity was the result of mixing of two lines, the 2774 ovarian cancer cell line, and the SW620 colon cancer cell line. Our results reinforce the necessity for accurate identification of cell lines. Also, that measurement of gene expression on a single cell level, for example by flow cytometric analysis, can be more informative than measurements of cell lysates, since the initial indication of heterogeneity would not have been detected by northern or western blotting. The different cell types retained characteristic growth patterns when injected i.p. in nude mice, i.e. peritoneal carcinomatosis and ascites formation by the 2774 ovarian cancer cells, and liver metastasis and growth of discrete abdominal tumors by the SW620 colon cancer.

Tumor-specific apoptosis induced by the human monoclonal antibody SC-1: a new therapeutical approach for stomach cancer.

Vollmers HP. Hensel F. Hermann R. Dammrich J. Wozniak E. Gessner P. Herrmann B. Zimmermann U. Muller-Hermelink HK.
Institut fur Pathologie, Universitat Wurzburg, Germany.
Stomach cancer is one of the most frequently occurring cancers worldwide, with a very poor prognosis, even after complete gastrectomy. We describe here an alternative therapeutical approach using a human monoclonal antibody (SC-1), which was isolated from a patient with diffuse-type gastric adenocarcinoma. We demonstrate that the antibody significantly reduces stomach cancer growth in vivo, by inducing tumor-specific apoptosis and that the antibody, even delivered in high doses, shows no toxic crossreactivity to other organs or tissues. The data presented here show that tumor-specific apoptosis can be induced and they give rise to the hope that human monoclonal antibodies with biological activity might present a completely new type of adjuvant cancer therapy.

Comparison of oral 5-HT3-receptor antagonists and low-dose oral metoclopramide plus i.m. dexamethasone for the prevention of delayed emesis in head and neck cancer patients receiving high-dose cisplatin.

Mantovani G. Maccio A. Curreli L. Lampis B. Ghiani M. Bianchi A. Contu P.
Department of Medical Oncology, University of Cagliari, Italy.
A phase III, single-institution, open, prospective, randomized, parallel study was carried out on head and neck cancer patients to compare a combination of low-dose (20 mg q.i.d.) oral metoclopramide (M) + i.m. Dexamethasone (D) with an oral 5-HT3-Receptor Antagonist (5-HT3-RA) alone in the prevention of high-dose (HD > or = 80 mg/m2) cisplatin-induced delayed emesis. 51 consecutive patients, all but two with advanced stage of disease, were treated for a total of 198 chemotherapic cycles: 23 patients entered Group A (5-HT3-RA) receiving a total of 108 cycles, 28 patients entered Group B (M + D) receiving a total of 90 cycles. The treatment groups were well matched for age, sex (almost all patients were males), ECOG PSR, stage of disease and alcohol intake. The efficacy of M + D was significantly higher than that of 5-HT3-RA in achieving complete protection (CR 88.9% vs 72.2%, chi2 9.9, p = 0.002) and major efficacy (ME: CR + MR) (94.5% vs 85.2%, chi2 5.6, p = 0.02). Generally, for both treatments (5-HT3-RA and M + D) a good control of delayed emesis was achieved in patients who had complete protection on acute emesis. A good control of acute emesis had a highly positive predictive value of delayed emesis for both treatments without significant difference between them (CR 85% for M + D and 82% for 5-HT3-RA; ME 88% for M + D and 92% for 5-HT3-RA). The failure (F) on acute emesis had a significantly higher negative predictive value of delayed emesis for M + D (98%) than 5-HT3-RA (67%). Our study is, to our knowledge, the first comparing M + D vs one 5-HT3-RA alone in the prevention of HD cisplatin-induced delayed emesis in a properly designed clinical trial. Our results show that M + D are more effective than 5-HT3-RA alone in the prevention of HD cisplatin induced delayed emesis, whereas 5-HT3-RA may be the treatment of choice in patients who had acute vomiting. Our study demonstrated not only the persistence of antiemetic efficacy but also increasing efficacy, during subsequent courses. Our results confirm that protection from acute emesis plays a major role in the appearance and control of delayed emesis.

Local recurrence of early esophageal carcinoma after endoscopic mucosal resection.

Kohakura M. Ban S. Harada H. Toyonaga A. Tanikawa K.
Department of Medicine II, Kurume University, School of Medicine, 67 Asahi-machi, Kurume City 830, Japan.
We performed endoscopic mucosal resection on 25 patients with early esophageal carcinoma where the depth of invasion was limited to in the lamina propria mucosae (m2) and we observed local recurrent cancer in 2 patients (8%). To reduce the rate of local recurrent cancer, the method of resection was aimed at pathological negative stumps and establishment of a strict standard of judgement on clinically complete resection were considered to be necessary. Furthermore, complete cure was possible even in patients with pathologically positive stumps in cases where no recurrent cancer was observed over a 1 year period following endoscopic mucosal resection.

Trans anal full thickness tru-cut needle biopsies in anal canal tumors after conservative treatment.

Indinnimeo M. Cicchini C. Stazi A. Mingazzini P. Ghini C. Pavone P.
I Clinica Chirurgica Policlinico, Universita di Roma, via del Policlinico 155, Rome, 00161, Italy.
After conservative treatment anal mucosal biopsies enable exclusion of neoplastic cells only on the endoluminal surface. We used transanal full thickness tru-cut needle biopsies in the follow-up of 11 anal tumors. Full thickness tru-cut needle biopsies showed malignant cells in the fibrous tissue in 3 patients and few cells with atypical nuclear features in another 2. All diagnostic exams resulted negative. Therefore, needle biopsies were helpful to diagnose neoplastic remainder. Multiple samples are necessary to reduce the false negative number. This method is simple, relatively inexpensive, easily repeatable and not burdened with complications.

Role of urokinase-type plasminogen activator in local immunotherapy.

Takeda T. Ito Y. Wakasugi E. Kobayashi T. Monden M.
Department of Surgery II, Osaka University, Medical School 2-2, Yamada-oka, Suita, Osaka, 565, Japan.
We have previously reported that intratumoral injection of a mixture of OK-432 and fibrinogen (OK/fbg) is very effective for local immunotherapy of colorectal cancer, but has little influence on breast cancer, while addition of activated macrophages to OK/fbg (OK/fbg/mo) has a marked effect on breast cancer. In this study, we analyzed the role of urokinase-type plasminogen activator (uPA) in local immunotherapy. We found that uPA levels in breast cancer tissue were lower than in colorectal cancer tissue. Injection of OK-432 into breast cancers neither increased the uPA level nor caused tumor regression. Although OK/fbg injection caused an increase of uPA, tumor regression was restricted to the area around the injection site. With OK/fbg/mo however, uPA levels increased much more markedly and extensive tumor necrosis was observed in all cases. These findings suggest that uPA plays an important role in tumor regression during local immunotherapy.

The expression of MMP-2 and TIMP-2 in patients with colorectal adenocarcinoma invaded to the submucosal and proper muscle layer.

Mukai M. Sadahiro S. Tokunaga N. Ishizu K. Ito I. Kameya T. Ishikawa K. Iwase H. Suzuki T. Kimura T. Ishida H. Tajima T. Makuuchi H.
Department of Surgery, Tokai University, School of Medicine, 8th Floor, Bohseidai, Isehara, Kanagawa, 259-1143, Japan.
The expression of MMP-2 and TIMP-2 was examined immunohistochemically in a total of 87 colorectal cancer patients. The expression of MMP-2 was in cancer cells: 76.5% (sm), 16.7% (pm), in cancer interstitial region: 92.2% (sm), 58.3% (pm), in transitional mucosal cells: 74.3% (sm), 17.1% (pm) and in transitional mucosal interstitial region: 80.0% (sm), 31.4% (pm). The expression of TIMP-2 was in cancer cells: 41.2% (sm), 16.7% (pm), in cancer interstitial region: 82.4% (sm), 69.4% (pm), in transitional mucosal cells: 57.1% (sm), 22.9% (pm) and in transitional mucosal interstitial region: 89.3% (sm), 57.1% (pm). These results suggest that the expression of MMP-2 and TIMP-2 is induced in the sm cancer stage and is closely related to interactions in the cancer interstitial region for invasion and metastasis in patients with colorectal adenocarcinoma.

Lymph node revealing solution: a new method for lymph node sampling: results in gastric adenocarcinoma.

Koren R. Kyzer S. Levin I. Klein B. Halpern M. Rath-Wolfson L. Paz A. Melloul MM. Mishali M. Gal R.
Department of Pathology, Rabin Medical Center (Campus Golda), Petah Tiqva and Sackler Faculty of Medicine, Tel Aviv University, Israel.
Staging of gastric carcinoma depends on exact lymph node status. However, very small nodes are not easily found as they are obscured by the surrounding adipose tissue. The purpose of the present study was to demonstrate the usefulness of a Olymph node revealing solutionO (LNRS) in gastric cancer. The perigastric adipose tissue of ten OproblematicO cases of gastric carcinoma, in which

Immunohistochemical demonstration of alpha-fetoprotein in small hepatocellular carcinoma.

Sato K. Tanaka M. Kusaba T. Fukuda H. Tanikawa K.
Second Department of Medicine, Kurume University School of Medicine, Asahi-machi 67, Kurume-shi, Fukuoka, 830, Japan.
We demonstrated immunohistochemical staining of a-fetoprotein (AFP) in small hepatocellular carcinoma (HCC). Fifty-six patients with HCC less than 2 cm in diameter were studied. Twenty-five HCCs (44.6%) were positive for AFP-staining. The positive rate of AFP-staining in HCC tissue was higher in the patients with serum AFP concentration above 20 ng/ml than that of the patients with below 20 ng/ml. AFP-staining was demonstrated on the rough endoplasmic reticulum of HCC cells by immuno-electron microscopy. AFP-staining of tissue specimens obtained by fine needle biopsy is useful in the histologic diagnosis of HCC.

Angiogenesis in esophageal squamous cell carcinoma.

Takebayashi Y. Natugoe S. Baba M. Fukumoto T. Takao S. Akiba S. Akiyama S. Aikou T.
First Department of Surgery, Department of Cancer Chemotherapy, Institute for Cancer Research, Kagoshima University, Sakuragaoka 8-35-1, Kagoshima 890, Japan.
We retrospectively analyzed the prognostic significance of angiogenesis and the relationships between tumor angiogenesis and clinopathological variables in a series of 127 patients with primary esophageal squamous cell carcinoma which were curatively resected. Vessels were stained with anti-factor VIII polyclonal antibody and areas with the highest number of microvessels were counted in a x400 field. Microvessel counts were significantly correlated with pN category, pM category, venous invasion and recurrence (p=0.002, p=0.040, p=0.016 and p=0.0013, respectively). The proportion of patients with recurrence increased in proportion to the number of microvessels. multivariate analysis using Cox's proportional hazard modelling showed angiogenesis assessed by microvessel count affected the poorer prognosis of patients with esophageal squamous cell carcinoma (hazard ratio, 1.03; 95%CI, 1.00-1.07), although it was not a significant independent prognostic factor (P=0.088). This study suggest that angiogenesis assessed by microvessel count is a marker for relapse and prognosis in patients with esophageal squamous cell carcinoma.

The expression of urokinase type plasminogen activator is a novel prognostic factor in dukes B and C colorectal cancer.

Kim SJ. Shiba E. Tsukamoto F. Izukura M. Taguchi T. Yoneda K. Tanji Y. Kimoto Y. Takai SI.
Department of Surgical Oncology, Osaka University, Medical School, 2-2 Yamadaoka, Suita City, Osaka 565, Japan.
Urokinase type plasminogen activator (u-PA) secreted by cancer cells is considered to play a key role in promoting invasion and metastasis of cancer cells. This study was designed to evaluate the expression and prognostic value of u-PA in Dukes B and C colorectal cancer. u-PA expression was investigated in 57 Dukes B or C colorectal cancers using a monoclonal antibody against u-PA. u-PA expression was mainly observed on the cytoplasm of cancer cells, and was associated with relapse, especially hematogenous metastasis (p=0.025, the chi2 test). Patients with high u-PA expression had a lower rate of DFS (9/22 events) compared to those with low u-PA expression (6/35 events) (p=0.061, log-rank test). This study demonstrated that u-PA expression might be a novel prognostic factor in Dukes B and C colorectal cancer.

Prognostic significance of c-myc mRNA expression assessed by semi-quantitative RT-PCR in patients with colorectal cancer.

Kakisako K. Miyahara M. Uchino S. Adachi Y. Kitano S.
Department of Surgery I, Oita Medical University, 1-1 Idaigaoka, Hasama-machi, Oita, 879-55, Japan.
To clarify the prognostic value of the c-myc oncogene mRNA expression levels in human colorectal cancer, samples obtained from 35 surgically resected tissues were examined by the semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Overexpression of c-myc mRNA was detected in 22 cases (63%). Although there was no correlation between c-myc overexpression and the depth of invasion, lymph node metastasis, or Dukes' stage, the patients with c-myc overexpression had metastatic recurrences significantly more frequently than those without it (29% versus 0%, p

Establishment and characterization of a new human extrahepatic bile duct carcinoma cell line (ICBD-1).

Takiyama I. Terashima M. Ikeda K. Kawamura H. Kashiwaba M. Tamura G. Suto T. Nakashima F. Sasaki R. Saito K.
Department of Surgery I, Iwate Medical University, School of Medicine, 19-1 Uchimaru, Marioka, 020, Japan.
A new human extrahepatic bile duct carcinoma cell line (ICBD-1) was established from surgically resected tumor of a 71-year-old Japanese male patient. ICBD-1 cells proliferate in a layer with a population doubling time of 31.5 h and secrete tissue polypeptide antigen. ICBD-1 cells have a tetraploid pattern with a DNA index of 1.83 and chromosome counts showed equally distribution in a range from 65 to 69. IC50 values for ICBD-1 cells were 200 ng/ml for adriamycin, 400 ng/ml for mitomycin C, 2 microg/ml for cisplatin and 300 ng/ml for 5-fluorouracil. ICBD-1 cells were successfully transplanted to male nude mice, inducing progressive tumor growth. Histologically, nude mouse tumors were less differentiated than the original human tumor. Tumor cells showed alveolar structures with thin fibrous stroma, classified as poorly-differentiated adenocarcinoma. ICBD-1 is the fourth established cell line that originate from extrahepatic bile duct carcinoma and it will be applicable for the experimental studies of this disease.

Comparison of p53 immunoexpression with allelic loss of p53 in ulcerative colitis-associated dysplasia and carcinoma.

Fogt F. Zhuang Z. Poremba C. Dockhorn-Dworniczak B. Vortmeyer A.
University of Pennsylvania, Presbyterian Medical Center, Department of Pathology, 39th and Market Street, Philadelphia, PA 19104, USA.
We correlated p53 overexpression with allelic deletion of p53 in ulcerative colitis (UC) with high grade dysplasia (HGD, n=12) and carcinoma (CA, n=8). Sections were immunostained against p53 and epithelium was microdissected on consecutive sections with subsequent amplification for LOH of p53 (17p). Staining with anti-p53 was positive in HGD (9 of 12) and CA (7 of 8). Percent positive cells were less in HGD than in CA. LOH of p53 was present in HGD (5 of 12) and CA (5 of 7). Of cases with

The clinicopathological characteristics and outcome of patients with right colon cancer.

Tomoda H. Taketomi A. Baba H. Kohnoe S. Seo Y. Saito T.
Department of Gastroenterological Surgery, National Kyushu Cancer Center, Notame, Minami-Ku, Fukuoka, 815, Japan.
We compared the characteristics between the 281 cases with right colon cancer (RCC) and 438 cases with left colon cancer (LCC) who underwent a resection for the disease at our hospital between 1972 and 1995. The mean patient age was significantly higher for RCC than for LCC (62.5 years vs 60.4 years). The mean tumor size was also significantly larger in RCC than in LCC (6.1 cm vs 4.8 cm). The type of recurrence or survival was similar between RCC and LCC. Elderly patients were also found to be more likely to develop RCC than younger patients. This cancer often grows to a large size before being diagnosed. These findings, therefore, suggest the need for targeted examinations for the early detection of RCC, especially in the elderly.

Induction of apoptosis in human stomach cancer cells by green tea catechins.

Hibasami H. Komiya T. Achiwa Y. Ohnishi K. Kojima T. Nakanishi K. Akashi K. Hara Y.
Faculty of Medicine, Mie University, Tsu-city, Mie 514, Japan.
The exposure of human stomach cancer KATO III cells to green tea catechin extract and epigallocatechin gallate (EGCG), a main component of the extract led to both growth inhibition and the induction of programmed cell death (apoptosis). Morphological changes showing apoptotic body were observed in the cells treated with green tea catechin extract and EGCG. The fragmentation of DNA to oligonucleosomal-sized fragments, characteristic of apoptosis was determined to be concentration- and time-dependent. These data suggest that drinking of green tea in large amounts is recommended possibly to protect humans from stomach cancer.

Adjuvant therapy for gastric adenocarcinoma with the apoptosis-inducing human monoclonal antibody SC-1: first clinical and histopathological results.

Year 1998
Vollmers HP. Zimmermann U. Krenn V. Timmermann W. Illert B. Hensel F. Hermann R. Thiede A. Wilhelm M. Ruckle-Lanz H. Reindl L. Muller-Hermelink HK.
Institut fur Pathologie, Josef-Schneider-Str. 2, Wurzburg, 97080, Germany.
In a first clinical trial with the apoptosis-inducing human antibody SC-1 eight patients with poorly differentiated stomach adenocarcinoma of diffuse-type received 20 or 30 mg of purified SC-1 antibody intravenously, followed 24 or 48 h later by gastrectomy and lymphadenectomy. In seven cases a significant induction of apoptotic activity was measured in primary tumors as compared with earlier biopsy material and in five patients a significant regression of tumor mass could be determined histopathologically. No toxic crossreactivity was observed with normal tissue or organs of patients.

The utility of monitoring carcinoembyronic antigen during systemic therapy for advanced colorectal cancer.

Year 1998
Grem JL. Steinberg SM. Chen AP. McAtee N. Cullen E. Hamilton JM. Allegra CJ.
NCI-Medicine Branch, NNMC, Building 8, Room 5101, 8901 Wisconsin Ave., Bethesda, MD, 20889-5105, USA.
To determine if pre-treatment serum carcinoembryonic antigen (CEA) levels or changes in CEA values during treatment have prognostic value, we reviewed five prior fluorouracil/leucovorin-based trials and identified 125 colorectal cancer patients with no prior chemotherapy for metastatic disease in whom CEA values were available. Although pre-treatment serum CEA values did not predict for clinical response or time to progression, serial monitoring of CEA appeared to be useful in patients with an elevated pre-treatment CEA, particularly when a decrease in CEA occurred in concert with radiographic evidence of disease response. The CEA nadir was a strong prognostic variable with respect to time to disease progression. A consistent rise in CEA values over the minimum value signals the need for radiographic re-assessment of the patient's disease status to rule out disease progression.

Effective program designed for long-term surveillance following colonoscopic polypectomy of adenomas.

Year 1998
Noguchi T. Asao T. Takenoshita SI. Nagamachi Y.
First Department of Surgery, Gunma University School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371 Japan.
Eighty-six patients who had adenoma and underwent colonoscopic polypectomy were examined by colonoscopy over a long period (mean follow-up time: 5 years) to establish an effective long-term surveillance program. The incidence of neogenetic lesions in patients with a large monoadenoma (diameter 0.5 cm; LA 69.7%) and polyadenoma (PA 74.2%) was higher than in those with a small monoadenoma (diameter

Assessment of small intestinal damage in patients treated with pelvic radiotherapy.

Year 1998
Carratu R. Secondulfo M. de Magistris L. Daniele B. Pignata S. D'Agostino L. Frezza P. Elmo M. Silvestro G. Sasso FS.
2nd University of Naples, Plaza Miraglia 1, Napoli, 80100, Italy.
Pelvic radiotherapy almost always induces intestinal symptoms. We investigated the radiation-induced damage to the small intestinal mucosa and evaluated its relationship with symptoms, using cellobiose/mannitol permeability test (CE/MA) and plasma postheparin diamine oxidase test (PHD) in 20 patients treated with pelvic radiotherapy. The symptoms developed during radiotherapy were noted. Intestinal permeability significantly (p=0.013) increased from 0.021 +/- 0.026 to 0.047 +/- 0.055 (mean +/- SD) after 15 days of radiotherapy, while it returned to normal values (0.010 0.015) at the end of radiotherapy. PHD values did not change. All patients developed intestinal symptoms. These findings indicate that pelvic radiotherapy induces an early small bowel mucosa damage followed by mucosal adaptation. Acute intestinal symptoms during pelvic radiotherapy may not depend only on small intestinal mucosal damage.

Carcinoembryonic antigen level in peritoneal washing is a prognostic factor in patients with gastric cancer.

Year 1998
Irinoda T. Terashima M. Takagane A. Sasaki N. Abe K. Araya M. Nishizuka S. Yonezawa H. Nakaya T. Shimooki O. Oyama K. Ikeda K. Saito K.
Department of Surgery I, Iwate Medical University, 19-1 Uchimaru, Morioka, Iwate 020, Japan.
This study was designed to evaluate the usefulness of carcinoembryonic antigen (CEA) and sialyl-Tn antigen (STN) levels in peritoneal washings in gastric cancer patients. At the time of laparotomy, peritoneal washings were collected from 96 gastric cancer patients and CEA and STN levels were determined. Patients with elevated CEA (100 ng/g protein) had a high incidence for peritoneal metastasis, lymph node metastasis and serosal invasion. In addition, prognosis in patients with high CEA level was significantly poorer than in those without it. The peritoneal CEA is a prognostic factor in patients with gastric cancer.

Studies on hyperthermia combined with arterial therapeutic blockade for treatment of tumors: (Part III) effectiveness of hyperthermia combined with arterial chemoembolization using degradable starch microspheres on advanced liver cancer.

Year 1998
Murata T. Akagi K. Imamura M. Nasu R. Kimura H. Nagata K. Tanaka Y.
Department of Radiology, Kansai Medical University, 10-15 Fumizonochou, Moriguchi City, Osaka, 570, Japan.
Arterial chemoembolization using degradable starch microspheres and adriamycin was combined with hyperthermia to treat advanced liver cancer. The prolonged peak adriamycin level in hepatic venous blood suggested that the drug persisted for longer in the liver after injection containing microspheres. Heating efficiency was increased more in tumor tissue than in normal liver tissue after embolization. This combined therapy was performed in eight patients with advanced liver cancer and was effective in three (complete or partial remission). The mean survival time was 25 weeks and there were no severe side effects. This combined therapy may be useful for liver cancer.

Onset of hepatocellular carcinoma in a non-cirrhotic patient affected with haemochromatosis.

Year 1998
Tomao S. Romiti A. Mozzicafreddo A. Raffaele M. Zullo A. Antonaci A.
IST, Istituto Nazionale per la ricerca sul cancro, Sezione di Roma, Via A. Baldovinetti 83, Rome, 00142, Italy.
The increased incidence of hepatocellular carcinoma in patients affected with haemochromatosis has previously been attributed to cirrhosis. However, some cases of hepatocellular carcinoma without cirrhosis have recently been reported in patients with haemochromatosis, leading to reconsideration of the role of iron in the tumorigenesis of hepatocellular carcinoma. We describe a 79 year old male patient affected with haemochromatosis and with a multinodular hepatocellular carcinoma, but without any evidence of cirrhosis. The absence of any other cancer risk factor (alcohol abuse, liver viral infections, heredity) has lead us to reconsider the possible role of iron as a direct carcinogen in the onset of hepatocellular carcinoma in patients with haemochromatosis.

NM23 gene product expression does not predict lymph node metastases or survival in young patients with colorectal cancer.

Year 1998
Heys SD. Langlois N. Smith IC. Walker LG. Eremin O.
Department of Surgery, Surgical Nutrition and Metabolism Unit, University Medical Buildings, Aberdeen Royal Infirmary, Aberdeen, AB9 2ZD, Scotland, UK.
NM23 gene product is a putative metastases suppressor gene which has structural homology to a nucleoside diphosphate kinase. Previous studies examining the relationship between NM23 gene product expression and survival in patients with colorectal cancer have revealed conflicting results. However, no study has focused on young patients with colorectal cancer. This study was carried out to determine if expression of the NM23 gene product was correlated with metastatic potential and survival in young patients (45 years and under) with colorectal cancer. Eighty- one patients with colorectal cancer were studied and the presence of the NM23 gene product (H1) was detected using standard immunohistochemical techniques. NM23 gene product expression did not correlate with tumour stage, lymph node involvement by tumour, presence of distant metastases, extramural vascular invasion or degree of tumour differentiation. Independent risk factors for overall survival were: Dukes' stage (p=0.00001) and extramural vascular invasion (p=0.003). NM23 expression was not an independent prognostic indicator (p=0.55). Therefore, NM23 expression does not correlate with existing indicators of tumour aggressiveness and behaviour nor is it an independent predictor of survival in young patients with colorectal cancer.

Immunohistochemical localization of metallothionein in hepatocellular carcinoma: preferential expression in non-cancerous cirrhotic nodules.

Year 1998
Tanimoto K. Akbar SM. Yamauchi Y. Michitaka K. Horiike N. Onji M.
Third Department of Internal Medicine, Ehime University School of Medicine, Shigenobu-Cho, Ehime 791-0295, Japan.
Metallothionein (MT), an oncofocal gene product was strongly expressed in 35%-95% of hepatocytes in hepatocellular carcinoma (HCC) and MT-positive hepatocytes were localized mainly in the non-cancerous cirrhotic nodules but not in malignant hepatocytes. On the other hand,

Clinicopathologic and immunohistochemical analyses in lung metastasis of colorectal carcinoma.

Year 1998
Koshiji M. Ogura E. Takada H. Kawanishi H. Ikehara S. Hioki K.
Second Department of Surgery and First Department of Pathology, Kansai Medical University, Moriguchi City, Osaka, Japan.
We compared the immunohistochemical staining patterns of carcinoembryogenic antigen (CEA), CA19-9 and proliferating cell nuclear antigen (PCNA) between specimens from 13 patients who had undergone surgery for colorectal carcinoma with lung metastasis (lung metastasis group) and specimens from 13 patients who had no evidence of recurrence or metastasis within at least 5 years after colorectal resection (no metastasis group). The PCNA labeling indices of primary and metastatic lesions were 53.29 8.88% and 63. 26 6.21% (p

Hepatocyte growth factor and Met/HGF receptors in patients with gastric adenocarcinoma.

Year 1998
Wu CW. Li AF. Chi CW. Chung WW. Liu TY. Lui WY. P'eng FK.
Department of Surgery, Veterans General Hospital-Taipei, Taipei, 11217 Taiwan, R.O.C.
Overexpression and amplification of Met/HGF receptor has been detected in gastric cancer tissues and cell lines. In this study hepatocyte growth factor (HGF) and Met/HGF receptors were localized in 32 gastric cancer and adjacent normal gastric tissues by the avidin-biotin-peroxidase complex technique. HGF (87.5%) and Met/HGF receptors (68.8%) were demonstrated in gastric cancer tissues. A high positive rate of HGF (87.0%) and Met/ HGF receptors (82.6%) presented in intestinal type gastric cancer. HGF immunoreactivity in gastric cancer tissues was a significant and powerful prognostic indicator (relative risk 15.9; p=0.01). These data suggest that HGF and Met/HGF receptors are involved in the morphogenesis of intestinal type gastric cancer. HGF may have other mechanism that favor gastric cancer spread and independently affect survival.

Immunisation of colorectal cancer patients with autologous tumour cells.

Year 1998
Diederichsen AC. Stenholm AC. Kronborg O. Fenger C. Jensenius JC. Zeuthen J. Kristensen T. Christensen PB.
Department of Clinical Immunology, Odense University Hospital, DK-5000 Odense C, Denmark.
Patients with colorectal cancer were entered into a clinical phase I trial of immunotherapy with an autologous tumour cell/bacillus Calmette-Guerin (BCG) vaccine. We attempted to describe the possible effects and side effects of the immunisation, and further to investigate whether expression of immune-response-related surface molecules on the tumour cells in the vaccine correlated with survival. The first and second vaccine comprised of 107 irradiated tumour cells mixed with BCG, the third of irradiated tumour cells only. Thirty-nine patients were considered, but only 6 patients fulfilled the criteria for inclusion. No serious side effects were observed. With three years of observation time, two patients are healthy, while the rest have had recurrence, and two of them have died. In all vaccines, all tumour cells expressed HLA class I, some expressed HLA class II and none expressed CD80. There was an inverse relation between survival and HLA class II expression. This highlights an essential problem, in the absence of CD80 expression the expression of HLA class II may induce anergy. In future attempts to develop improved vaccines this problem should be addressed.

A case of biliary cystadenoma with obstructive jaundice.

Year 1998
Taketomi A. Tamada R. Takenaka K. Kawano R. Maeda T. Sugimachi K.
Department of Gastroenterological Surgery, National Kyushu Cancer Center, Fukuoka 811-1395, Japan.
Biliary cystadenoma is a rare cause of obstructive jaundice. We report a case of a 78-year-old Japanese man with biliary cystadenoma presenting repetitive abdominal pain and jaundice. Ultrasound sonography revealed a hyperechoic mass in the left lateral lobe of the liver. Histological examination revealed a biliary cystadenoma. Intracystic hemorrhage was assumed to be the cause of obstruction of the bile ducts.

Ki-67 antigen expression in relation to clinicopathological variables and prognosis in gastric cancer.

Year 1998
Kikuyama S. Kubota T. Shimizu K. Miyakita M.
Department of Surgery, Saiseikai Central Hospital, Minato-ku, Tokyo 108-0073, Japan.
One hundred and thirty surgical specimens of gastric adenocarcinoma were obtained from patients who had undergone radical gastrectomy. The samples were formalin-fixed, paraffin-embedded and used for immunostaining of Ki-67 antigen. Mean Ki-67 index was 41.8% (SD 15. 7%, range 8.2-84.2%). Differentiated carcinomas had a higher Ki-67 index than undifferentiated tumors, although other clinicopathological variables, including lymph node metastasis and depth of invasion showed no correlation with Ki-67 index. In the undifferentiated tumors, Ki-67 index correlated with lymph node involvement. A high Ki-67 index ( 55%) was found to be an independent indicator of poor prognosis in patients with undifferentiated tumors.

Detection of serum p53 antibodies in patients with esophageal squamous cell carcinoma: correlation with clinicopathologic features and tumor markers.

Year 1998
Shimada H. Nakajima K. Ochiai T. Koide Y. Okazumi SI. Matsubara H. Takeda A. Miyazawa Y. Arima M. Isono K.
Department of Surgery, School of Medicine, Chiba University, Chuou-ku, Chiba 260-8670, Japan.
The significance of serum p53-Abs in patients with esophageal squamous cell carcinoma was determined. Examination of clinicopathological features and assessment of tumor marker sensitivities of carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC-Ag) and CYFRA21-1 were performed. Thirty-three (58%) of 57 patients were positive for serum p53-Abs, however, no relation with cancer progression existed. Fourteen of the 33 sero-positive patients revealed normal levels of all tumor markers tested. Thus, serum p53-Abs appears to be a useful marker for the detection of esophageal squamous cell carcinoma.

Prognostic value of low density lipoprotein receptor expression in colorectal carcinoma.

Year 1998
Caruso MG. Osella AR. Notarnicola M. Berloco P. Leo S. Bonfiglio C. Di Leo A.
Laboratorio di Biochimica, IRCCS Castellana Grotte, Bari, Italy.
Cancer cells require more cholesterol than normal cells. This requirement seems to be satisfied by a higher HMG-CoA reductase activity or a higher activity of low density lipoprotein receptor (LDLR). We investigated the prognostic value of LDLR in colorectal carcinoma (CRC) patients. The LDLR was evaluated in 90 patients with CRC by ELISA. The survival time and the relative risk of prognostic factors were analyzed by Kaplan-Meier estimates and Cox proportional hazard model. Thirty three cases were LDLR positive (+), while 57 LDLR negative (-). The survival of LDLR(-) patients was shorter than that of LDLR(+). By Cox model, the absence of LDLR and time until metastasis resulted significantly associated with the CRC-related survival. The absence of LDLR in CRC predicts a shorter survival.

Single-dose etoposide in advanced pancreatic and biliary cancer, a phase II study.

Year 1998
Ekstrom K. Hoffman K. Linne T. Eriksson B. Glimelius B.
Department of Oncology, University Hospital, S-751 85 Uppsala, Sweden.
Palliative chemotherapy can add to the duration and quality of life in patients with advanced pancreatic and biliary cancer, albeit in a limited way. Between March 1995 and October 1997, 31 symptomatic patients were treated with etoposide in a phase II trial. Measurements of objective and subjective responses were performed, the latter by the treating physician and with the method of clinical benefit response (CBR). Quality of life was evaluated with the EORTC QLQ-C30 questionnaire. A partial response was seen in 2 (6%) patients. Subjective responses/quality of life gains were seen in 6 (19%), 7 (23%) and 9 (29%) patients, respectively, with the different methods. Median survival was 4.5 months. WHO grade 3 and 4 toxicity, alopecia excluded, was seen in 20% of the patients. The clinical activity of etoposide is limited, and in the same low range as other drugs in these diseases.

Early gastric cancer in the province of Forli: follow-up of 337 patients in a high risk region for gastric cancer.

Year 1998
Saragoni L. Gaudio M. Vio A. Folli S. Nanni O. Saragoni A.
Department of Pathology,'Morgagni-Pierantoni' Hospital, Forli 47100, Italy.
Long-term clinical outcome was analysed in a series of 337 patients with early gastric cancer (EGC) at a median follow-up of 8 years. Tumours were classified according to the macroscopic and microscopic criteria proposed by the Japanese society of gastroenterological endoscopy (JSGE) and Lauren, respectively. Type of penetration (PEN) was classified according to Kodama. Overall survival rate was 92% at 5 years and 88% at 8 years and was significantly related to depth, type of penetration, lymph node status and tumour size. A significantly lower 5-year survival (p

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