bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Hormone Replacement Therapy on Selected Indices of Immune Function in Postmenopausal Women
Authors: Fahlman Mariane M. , Boardley Debra , Flynn Michael G. , Bouillon Lucinda E. , Lambert Charles P. , Braun William A.
Published: April 2003

The purpose of this study was to examine the effects of long-term hormone replacement therapy (HRT) on selected indices of resting immune function in postmenopausal women. Postmenopausal women aged 54–66 were divided into two groups, those taking HRT (n = 17) and controls (n = 19). Blood samples were obtained and analyzed for mononuclear cell numbers, lymphocyte proliferation (LP) and natural cell-mediated cytotoxicity (NCMC). There were no significant differences between groups for mononuclear cell numbers. LP was significantly higher for HRT, while NCMC was significantly lower for HRT. HRT is currently being prescribed to postmenopausal women for prevention of a variety of medical conditions including osteoporosis, cardiovascular disease, stroke, and Alzheimer’s disease yet HRT is often associated with altered immune parameters. In this study, women taking HRT had increased lymphocyte blastogenesis and decreased NCMC compared to controls.
Pure versus Complicated Vulvar Vestibulitis: A Randomized Trial of Fluconazole Treatment
Authors: Bornstein Jacob , Livnat Galit , Stolar Zmira , Abramovici Haim
Published: April 2003

Objective: To examine the effectiveness of a 6-month treatment consisting of a weekly oral dose of 150 mg fluconazole for women with vestibulitis, and to explore the causes of treatment failure. Methods: Forty women with vestibulitis were randomized to either of two treatment groups. One group received a 6-month low oxalate diet with calcium citrate complement, as a placebo, and the second group the same diet and calcium citrate with the addition of a weekly oral tablet of 150 mg fluconazole. The women were examined 3 months after completing treatment, for response to therapy. Results: The addition of intensive 6-month fluconazole treatment did not lead to an outcome better than that attained by maintaining a low oxalate diet with calcium citrate supplementation. The satisfactory response rate was 15 and 30%, respectively. The presence of ‘complicated vestibulitis’, candidiasis concomitant with vestibulitis, decreases the satisfactory response rate regardless of the type of treatment administered (odds ratio 19.9, 95% CI 1.6, 250). Conclusion: Prolonged oral fluconazole is an ineffective treatment of vestibulitis, whether pure or complicated by concomitant vulvovaginal candidiasis. The coexistence of candidiasis and vestibulitis – complicated vestibulitis – might represent a subset of vestibulitis that is resistant to the currently available medical therapy.
Expression of Constitutively Active c-MET Receptor in Human Choriocarcinoma
Authors: Takayanagi Takeshi , Aoki Yoichi , Tanaka Kenichi
Published: April 2003

Objective: The c-MET oncogene encodes the transmembrane tyrosine kinase receptor for hepatocyte growth factor (HGF). Recently, either HGF or c-MET has been knocked out in the mouse, and the mutation is associated with defects in the development of the placenta by means of the reduction of trophoblast cells. We examined the role of c-MET in malignant transformation of trophoblast cells. Methods: In four human choriocarcinoma cell lines, GCH-1, GCH-1m, NUC-1 and SCH, the expression of HGF and c-MET was analyzed by RT-PCR and Western blotting using anti-c-MET antibody and antiphosphotyrosine antibody. Results: RT-PCR analysis showed that no cell lines expressed HGF, however all the cell lines revealed the expression of c-MET mRNA. c-MET receptor was expressed and also tyrosine-phosphorylated constitutively in these cell lines by Western blotting. Conclusion: These results suggest that c-MET may be involved in the growth and behavior of human choriocarcinoma although an autocrine fashion of HGF is unlikely.
Nausea and Vomiting in Pregnancy: An Association between Symptoms and Maternal Prostaglandin E2
Authors: Gadsby Roger , Barnie-Adshead Anthony , Grammatoppoulos Dimitri , Gadsby Pam
Published: April 2003

This study investigated the aetiology of nausea and vomiting in pregnancy (NVP) in primary care using a new methodology. Eighteen women in early pregnancy had 2 blood samples taken in one 24-hour time period, one when they were symptomatic, and another when they were symptom-free. Maternal serum levels of the candidate agents PGE2, IL-1β, and TNFα were measured. The study shows a positive relationship between NVP and maternal serum PGE2 levels in early pregnancy.
The Role of Angiogenesis in the Accumulation of Peritoneal Fluid in Benign Conditions and the Development of Malignant Ascites in the Female
Authors: Sherer David M. , Eliakim Rami , Abulafia Ovadia
Published: April 2003

Our objective was to present current data pertaining to the role of angiogenesis in the accumulation of peritoneal fluid in both benign conditions and in the development of malignant ascites in the female. To this goal, we conducted a computerized search to identify all relevant studies published in the English literature. MEDLINE, Current Contents and Index Medicus were searched utilizing the terms: angiogenesis, peritoneal fluid, ascites, vascular endothelial growth factor (VEGF), therapy and carcinoma through May 2000. Review of the literature supports that angiogenesis promoted by VEGF is associated with fluid accumulation in animal and human tumor effusions. Benign conditions involving accumulation of peritoneal fluid and associated angiogenesis in the female include ovulation, endometriosis and severe ovarian hyperstimulation syndrome. Malignant intra-abdominal conditions associated with increased VEGF activity include primary epithelial ovarian, gastric and colon carcinomas, omental and hepatic metastatic disease. Initial trials with antiangiogenic (angioinhibitor) therapy such as anti-VEGF antibodies, anti-VEGF receptor antibodies, tumor necrosis factor, and metalloproteinase inhibitors have been reported and antitumor activity observed in a limited number of patients with advanced (inoperable or metastatic) disease.
Impact of Maternal Anthropometry and Smoking on Neonatal Birth Weight
Authors: Laml Thomas , Hartmann Beda W. , Kirchengast Sylvia , Preyer Oliver , Albrecht Alexander E. , Husslein Peter W.
Published: April 2003

The purpose of this study was to determine the effect of maternal pre-pregnancy body mass index (BMI) and maternal smoking habits on neonatal birth weight. We reviewed 10,240 normal singleton term pregnancies between 1985 and 1995 at the University Department of Obstetrics and Gynecology, Vienna. Birth weights of infants of overweight smokers were greater than those of smokers in general and similar to birth weights of nonsmokers, but smoking did have a fetal growth-retarding effect in overweight smoking mothers. Infants of underweight mothers who increased their daily cigarette consumption during pregnancy had significantly lowest birth weight. Our results suggest that the negative effects of smoking during pregnancy cannot be mitigated by a higher pre-pregnancy BMI and/or an improved weight gain during pregnancy. Especially the infants of underweight mothers benefit from their mothers’ decision to cease smoking.
Prothrombin G20210A Mutation: Is It Associated with Pre-Eclampsia?
Authors: Higgins John R. , Kaiser Thomas , Moses Eric K. , North Robyn , Brennecke Shaun P.
Published: April 2003

Objective: A strong independent association between the prothrombin G20210A gene mutation and pre-eclampsia has been reported in an Italian population. This result was not confirmed in a subsequent study in a Dutch population. The objective of this study was to further test the hypothesis that the prothrombin G20210A mutation is associated with pre-eclampsia/eclampsia. Methods: Seventeen eclamptics and 67 pre-eclamptics were recruited from 34 multicase Australian/New Zealand families. An additional 105 unrelated pre-eclamptic/eclamptic women and 119 parous women were recruited as controls. Results: The overall incidence for the prothrombin G20210A gene mutation in the pre-eclamptic group was 3.6% (95% CI 1.2–8.2%) which was not significantly different from the control group 2.5% (95% CI 0.5–7.2%) (p = 0.73, OR 1.44, 95% CI 0.34–6.17). Conclusion: This study provides little evidence of a significant relationship between the prothrombin G20210A gene mutation and pre-eclampsia. Based on our results, we do not recommend testing for the prothrombin G20210A mutation in the routine investigation of women with pre-eclampsia.
Reversal of Intra-AmnioticChlamydia trachomatis Ant igen Status
Authors: Yoshida Hiroshi , Yamada Hideto , Wada Shinichiro , Sagawa Tadashi , Sakuragi Noriaki , Fujimoto Seiichiro
Published: April 2003

Chlamydia trachomatis (CT) infection in pregnant women is related to unfavorable obstetric outcomes such as prematurity, intrauterine growth retardation, and stillbirth. A 22-year-old woman underwent transabdominal amniocentesis at 16 weeks of gestation (GW). A CT antigen test using polymerase chain reaction in the amniotic fluid was found to be positive, though the patient had no symptom of infection. Beginning at 20 GW, clarithromycin was orally administered at a dose of 400 mg/day for 2 weeks. The CT antigen test in amniotic fluid at 28 GW turned to a negative result. A female baby was vaginally born at 38 GW by spontaneous labor. The CT antigen test of her gastric contents showed a negative result and anti-CT IgM in umbilical cord blood was negative. Neither respiratory distress, pneumonia, nor conjunctivitis was detected. To the best of our knowledge, this case is the first report showing the reversal of the intra-amniotic CT antigen status by antibiotic treatment.
The Prognostic Significance of c-erbB-2 Serum Protein in Metastatic Breast Cancer
Authors: Fehm Tanja , Maimonis Peter , Katalinic Alexander , Jäger Wolfram H.
Published: April 2003

The relationship between c-erbB-2 serum positivity and prognosis was evaluated in 80 patients with metastatic breast cancer. Using 120 fmol/ml as a cutoff level, elevated concentrations were found in 31 patients (38.8%) at the time of detection of metastases. Menopausal status, steroid receptor status, site of recurrence, initial tumor size, initial degree of nodal involvement as well as relapse-free interval were unrelated to c-erbB-2 serum positivity. In addition, no association could be found between adjuvant chemotherapy and positive c-erbB-2 concentrations. Patients with elevated c-erbB-2 levels showed a lower response rate (including complete remission, partial remission, no change) to first-line therapy than those with normal levels (29 vs. 59%, p < 0.01). The median survival time after relapse was 12 months (CI: 3–22 months) for the c-erbB-2-negative patients and only 6 months (CI: 3–8 months) for the c-erbB-2-positive group (p < 0.01). In the multivariate analysis, while c-erbB-2 levels at the time of primary surgery had no significant impact on survival in metastatic breast cancer, serum c-erbB-2 turned out to be the strongest factor for predicting survival after relapse.
Phase II Trial of Navelbine and Fluorouracil as Second-Line Chemotherapy in Metastatic Breast Carcinoma
Authors: Froudarakis Marios E. , Catimel Gilles , Guastalla Jean-Paul , Rebattu Paul , Clavel Michel
Published: April 2003

Vinorelbine [Navelbine® (NVB); Fabre, Castres, France] is a semisynthetic vinca alkaloid. Efficacy and tolerance of vinorelbine were investigated in patients with metastatic breast carcinoma (MBC), with encouraging results, in several studies of first- or second-line therapy alone [1–3], and in combination with other drugs [4–6]. The effectiveness of 5-fluorouracil (5FU) in adenocarcinomas is well known [7]. Based on these results, we initiated a phase II trial of an NVB and 5FU combination in patients with MBC [8]. The aim was to explore the effectiveness and toxicity of this combination.
Assessment of p53 Protein Expression in Normal Mucosa and Benign and Malignant Lesions of the Nasal Cavity
Authors: Fang Sheen-Yie , Yan Jin-Jou , Ohyama Masuru
Published: April 2003

p53 gene mutation is documented in head and neck cancer. No reports exist relating this mutation to normal mucosa or benign and malignant lesions of the nasal cavity. We investigate p53 overexpression using immunohistochemical techniques improved by an antigen retrieval method. p53 protein was analyzed in the following cases: normal, benign [papilloma and inverted papilloma (IP)] and malignant [squamous-cell carcinoma (SCC) arising in IP, SCC alone, adenocarcinoma and small-cell carcinoma]. Both the intensity and rate of positive p53 immunostaining were evaluated using a quantitative AutoCAD program. Overexpression of p53 protein was not identified in normal mucosa, benign or premalignant lesions; however, approximately 60% is correlated to nasal cancer. p53 overexpression correlates with heavy smoking. Both the IP and SCC portions of SCC synchronous with IP showed similar p53 immunoreactivity. SCC arising in IP shows a lower p53 immunoreactivity than SCC alone. Thus, smoking along with a p53 mutation may be a mutagenic agent in nasal cancers. Alteration of the p53 protein may play an important role in the early stages of the malignant transformation of IP. A low p53 immunoreactivity indicates the presence of wild-type p53 protein. This may show a better response to radiation therapy yielding a better prognosis for SCC arising in IP compared to SCC alone. However, further clinical trials are required to investigate this possibly worthwhile prognostic marker.
Comparative Survival Analysis of p53 Gene Mutations and Protein Accumulation in Colorectal Cancer
Authors: Caldes Trinidad , Iniesta Pilar , Vega Francisco J. , de Juan Carmen , Lopez Jose A. , Diaz-Rubio Eduardo , Fernandez Cristina , Cerdan Javier , Balibrea Jose L. , Benito Manuel
Published: April 2003

Immunohistochemical reactivity for p53 protein is common in various human malignancies. Increased intracellular concentration of p53, which is frequently, but not systematically, related to p53 mutation, has been proposed to be associated with poor prognosis in some tumor types. In colorectal cancer, this significance is still a matter of debate. To directly investigate the relationship between prognosis and p53 alterations, we screened a series of 72 colorectal carcinomas for overexpression and mutation of the p53 gene. Mutations in exons 5–9 of the p53 gene were assayed by single-strand conformation polymorphism and direct DNA sequencing, whereas p53 protein accumulation was detected in 10-µm frozen tissue by immunostaining using 2 different monoclonal antibodies (PAb 1801 and DO7). Thirty-six tumors (50%) showed p53 overexpression. Nineteen of the 36 tumors which contained high levels of p53 protein were found to have missense point mutations. Using a multivariate survival analysis, stage, differentiation, p53 immunoreactivity and p53 mutation emerged as risk factors, but only the stage was significant. In univariate analysis, stage, differentiation and p53 immunoreactivity were significant prognostic indicators, while p53 mutation was at the borderline of significance.
Transarterial Chemotherapy with Zinostatin Stimalamer for Hepatocellular Carcinoma
Authors: Okusaka Takuji , Okada Shuichi , Ishii Hiroshi , Ikeda Masafumi , Nakasuka Hidekazu , Nagahama Hiroyasu , Iwata Ryoko , Furukawa Hiroyoshi , Takayasu Kenichi , Nakanishi Yukihiro , Sakamoto Michiie , Hirohashi Setsuo , Yoshimori Masayoshi
Published: April 2003

Zinostatin stimalamer (SMANCS) is a lipophilic intra-arterial chemotherapeutic agent for hepatocellular carcinoma (HCC). Thirty HCC patients underwent transcatheter arterial injection of 4 mg SMANCS-lipiodol emulsion. Their responses were evaluated by computed tomography 1 month after treatment. Complete response (CR) was defined as disappearance or 100% necrosis of all tumors. Partial response (PR) was defined as ≧50% reduction and/or ≧50% necrosis. We regarded the lipiodol accumulation in tumors as being necrotic. CR and PR were observed in 8 patients (27%) and 4 patients (13%), respectively, and the overall response rate (CR + PR/all patients) was 40% (12/30). Of 12 patients whose serum α-fetoprotein levels had been more than 200 ng/ml before treatment, 5 patients (42%) showed more than 50% reduction in this level within 1 month after treatment. Toxicity was quite acceptable, although grade 4 toxicity (WHO) was observed as liver dysfunction in 1 patient. Transarterial chemotherapy with SMANCS, which is well tolerated, appears to have moderate antitumor effect in patients with HCC.
Prognostic Value of DNA Ploidy and Proliferating Cell Nuclear Antigen in Gastric Cancer
Authors: Hirose Kazuo , Iida Atsushi , Yamaguchi Akio , Onchi Hidetoshi , Awata Hirofumi , Katayama Kanji , Nakagawara Gizo
Published: April 2003

DNA ploidy and the labeling index (LI) of proliferating cell nuclear antigen (PCNA) in gastric cancers were determined using cytofluorometry and immunohistochemistry, respectively, and the prognostic value of these two parameters was evaluated. Of 66 patients with advanced gastric cancers treated with radical resection, 27 with aneuploidy and a high PCNA-LI (≧40) showed the lowest 5-year survival rate (38%). Twenty patients with diploid cancers and a high LI showed a lower 5-year survival rate (59%) than the 15 patients with diploid cancers and a low LI (<40), who had the highest 5-year survival rate (86%). A multivariate analysis showed that the grouping based on the ploidy and the LI was an independent prognostic factor. Thus, the combination of DNA ploidy and PCNA-LI may be a useful prognostic indicator for advanced gastric cancers.
Immunoreactive MUC1 Expression at the Deepest Invasive Portion Correlates with Prognosis of Colorectal Cancer
Authors: Hiraga Yuko , Tanaka Shinji , Haruma Ken , Yoshihara Masaharu , Sumii Koji , Kajiyama Goro , Shimamoto Fumio , Kohno Nobuoki
Published: April 2003

This study sought to examine the relationship between MUC1 expression at the deepest invasive portion, invasive/metastatic potential, and prognosis of colorectal cancer in relation to cellular proliferation. MUC1 expression was detected immunohistochemically using KL-6 antibody (anti-MUC1 monoclonal antibody) in 100 surgically resected specimens of advanced colorectal cancer. Distinct staining of the luminal surfaces, defined as positive immunoreactive (IR)-MUC1 expression, was seen in more than 30% of the tumor cells at the deepest invasive portion. The proliferating cell nuclear antigen labeling index (PCNA-LI) was also examined in the same areas. IR-MUC1 expression was detected in 71 (71%) of 100 lesions. Lesions with lymphatic or venous invasion showed a significantly higher incidence of IR-MUC1 expression than those without lymphatic or venous invasion (80 vs. 42% and 82 vs. 61%, respectively). Lesions with lymph node metastasis showed a significantly higher incidence of IR-MUC1 expression than those without lymph node metastasis (88 vs. 53%). Lesions with liver metastasis showed a significantly higher incidence of IR-MUC1 expression than those without liver metastasis (92 vs. 59%). Dukes’ stage was also significantly correlated with IR-MUC1 expression. The incidence of IR-MUC1 expression did not significantly differ with regard to histologic subclassification and depth of invasion. There was no significant correlation between IR-MUC1 expression and the PCNA-LI. IR-MUC1 expression at the deepest invasive portion revealed a significant correlation with prognosis; furthermore, in patients with better differentiated lesions, in those with lesions confined to muscularis propria or subserosa (subadventitial) invasion, in those with Dukes’ B and C, or in those undergoing curative resection, IR-MUC1 expression significantly correlated with prognosis. Patients with high PCNA-LI lesions showed a significantly poorer prognosis than those with low PCNA-LI lesions. Only in patients undergoing curative resection, patients with IR-MUC1-positive and high PCNA-LI lesions showed a significantly poorer prognosis than those with IR-MUC1-negative and low PCNA-LI lesions. The significant risk factors in the order of poorer prognosis in patients undergoing curative resection by the multivariate analysis were the histologic grade (moderately–poorly, poorly or mucinous adenocarcinomas), IR-MUC1 expression, and lymph node metastasis. These results indicate that IR-MUC1 expression is an important predictor of the metastatic potential and the prognosis of colorectal cancer, independent of histologic grade, depth of invasion or cellular proliferative activity. Combined analysis of IR-MUC1 and histologic grade, and combined expression of IR-MUC1 and PCNA at the deepest invasive portion are especially useful in predicting colorectal cancer prognosis.
Prognostic Value of nm23 Protein Expression in Renal Cell Carcinomas
Authors: Nakagawa Yoshinori , Tsumatani Kenichi , Kurumatani Norio , Cho Masaki , Kitahori Yoshiteru , Konishi Noboru , Ozono Seiichiro , Okajima Eigoro , Hirao Yoshihiko , Hiasa Yoshio
Published: April 2003

In the present study, an analysis of whether expression of nm23-H1 and nm23-H2 proteins has prognostic significance was performed. A series of 95 renal cell carcinomas was analyzed for nuclear grade, tumor size (larger than 50 mm or not), staging in the Robson system and expression of nm23-H1 and nm23-H2, as well as patient survival. Immunohistochemical staining of nm23-H1 and nm23-H2 was found in 68.4 and 50.5% of the cases, respectively. Significant differences in nm23-H1, but not nm23-H2 expression were noted with regard to nuclear grade and tumor size. The patients with nm23-H1-expression-negative tumors sized ≤50 mm had a significantly poorer prognosis than their positive counterparts. Multivariate analysis using the Cox proportional hazards regression model indicated that the staging in the Robson system and expression of nm23-H1 were significant and independent prognostic factors for survival. However, no significant correlation between the incidence of metastasis and expression of nm23-H1 or nm23-H2 was found. The results imply that reduced expression of nm23-H1 influences the prognosis of patients with renal cell carcinomas, but not the likelihood of metastasis. In small tumors sized ≤50 mm, reduced expression of nm23-H1 protein was suggested to be an especially strong predictor of a poor prognosis.
Proliferating Cell Nuclear Antigen Immunoreactivity and the Presence of P53 Mutation in Basaloid Squamous Cell Carcinoma of the Larynx
Authors: Akyol Mehmet Umut , Dursun Ayşe , Akyol Gülen , Edalι Naci
Published: April 2003

Basaloid squamous cell carcinoma (BSCC) is an aggressive variant of squamous cell carcinoma (SCC) that was first described in 1986. In the English literature, only 28 cases of this histopathological entity have been reported in the larynx. Proliferative features of this infrequent tumor were investigated by proliferating cell nuclear antigen immunoreactivity, and the presence of P53 mutation was also investigated in a series of 4 cases. BSCC was found to share similar features with regular SCC in terms of its proliferation rate and P53 mutation positivity, as well as biological behavior and clinical outcome.
Fadrozole versus Megestrol Acetate: A Double-Blind Randomised Trial in Advanced Breast Cancer
Authors: Bezwoda W.R. , Gudgeon A. , Falkson G. , Jordaan J.P. , Goedhals L.
Published: April 2003

Ninety-six patients were entered into a randomised, double-blind, double-dummy, clinical trial to assess the efficacy and safety of fadrozole as compared to megestrol acetate as second-line hormonal treatment for patients with advanced breast cancer. Analysis of results was on an intention-to-treat basis and included response rate, time to progression (TTP), time to treatment failure (TTF) and survival. Forty-six patients received fadrozole and 50 were randomised to megestrol acetate. Patients and pretreatment prognostic variables were balanced in the two arms of the trial. The objective response rates [3/46 (7%) for fadrozole and 3/50 (6%) for megestrol acetate], TTP, TTF and survival were similar in the two arms of the trial. Toxicity was also similar in the two arms of the trial and consisted mainly of oedema, hypertension and minor gastrointestinal symptoms. Fadrozole appears to be as active as megestrol acetate in second-line hormonal treatment of advanced breast cancer.
Combination Regimen with Carboplatin, Epirubicin and Etoposide in Metastatic Carcinomas of Unknown Primary Site: A Hellenic Co-Operative Oncology Group Phase II Study
Authors: Briasoulis Evangelos , Tsavaris Nicholas , Fountzilas George , Athanasiadis Athanasios , Kosmidis Paris , Bafaloukos Dimitris , Skarlos Dimosthenis , Samantas Epaminondas , Pavlidis Nicholas
Published: April 2003

The encouraging results that have been reported for cisplatin combination chemotherapy in a minority of patients with cancer of unknown primary (CUP) together with the previously shown equal activity of carboplatin in this setting, prompted us to investigate the effectiveness of a carboplatin-containing regimen in a phase II clinical trial.Sixty-two evaluable CUP patients entered the protocol. The chemotherapy regimen consisted of carboplatin 300 mg/m2 IV D1, epirubicin 45 mg/m2 IV D1 and etoposide 120 mg/m2 IV D1–3 (CEE regimen) administered every 3 weeks. The median age of the patients was 61 years and 36 were male. Thirty-one diagnosed as poorly differentiated carcinomas (pdc) and the rest as adenocarcinomas. By clinicopathological criteria, 14 patients had a predominately nodal disease with pdc or poorly differentiated adenocarcinomas (pda), 3 women peritoneal carcinomatosis, and the remaining 46 patients had a predominately splanchnic involvement (24 pdc, 22 pda). Twenty-three patients responded to chemotherapy with 4 (6.5%) complete and 19 (30.5%) partial responders (RR 37%, 95% CI 25–49%). An equal activity of the regimen was observed between the two major histopathological types, the pdc and the adenocarcinomas. Nevertheless, significant differences were seen when the CEE regimen was assessed for its activity in the distinct clinicopathological subsets of CUP. Patients with predominately nodal disease of midline distribution with pdc or pda, and women with peritoneal carcinomatosis, achieved a response rate of 64 and 62% respectively, as compared with a 26% response rate for those with predominately splanchnic involvement. Overall median survival was 10 months and for patients with midline distribution 15 months. The regimen was well tolerated. It is concluded that CEE is a relatively nontoxic chemotherapy regimen and easily administered on an outpatient basis. This prospective phase II study confirmed the activity of carboplatin in the chemosensitive subsets of the predominately nodal disease of midline distribution and peritoneal carcinomatosis in women in the CUP syndrome.
Topotecan – A Novel Topoisomerase I Inhibitor: Pharmacology and Clinical Experience
Authors: Kollmannsberger C. , Mross K. , Jakob A. , Kanz L. , Bokemeyer C.
Published: April 2003

Topotecan, a water-soluble analogue of camptothecin, is a newly available cytotoxic agent which acts as an inhibitor of topoisomerase I, an enzyme necessary for DNA replication. Topotecan is a semisynthetic product derived from camptothecin, which was discovered during a National Cancer Institute cytotoxic drug screening program almost 30 years ago. It acts by forming a stable covalent complex with the DNA/topoisomerase I aggregate, the so-called ‘cleavable complex’. This process leads to breaks in the DNA strand resulting in apoptosis and cell death. Topotecan possesses a serum half-life of approximately 3 h, a high volume of distribution with high tissue uptake and a low protein binding. The chemical structure is based on a lactone ring. Topotecan undergoes reversible hydrolysis from its biologically active lactone form to the open ring inactive carboxylate form. It is also able to penetrate the intact blood-brain barrier. Since most of the agent is excreted by the kidneys, dose adjustment is necessary when renal function is impaired. In contrast, pharmacokinetic behavior is unchanged in patients with limited hepatic function. The principal toxicity of topotecan when administered at standard doses is neutropenia, but thrombocytopenia and anemia occur as well, while the nonhematological toxicities are usually mild. Alopecia is frequently observed and some patients may suffer from pronounced fatigue. Most clinical data available are based on the following schedule: 1.5 mg/m2 topotecan given as a 30-min infusion, days 1–5. There are currently only minimal data available regarding a dose–antitumor activity relationship. Other topotecan administration schedules are currently being investigated. Preclinical data suggest that continuous-infusion schedules may be a better application form in terms of both, toxicity and antitumor activity. However, clinical trials could not confirm these results to date. Results of phase II studies suggest considerable antitumor activity of single agent topotecan in small cell lung cancer and ovarian cancer patients. A randomized phase III trial of topotecan versus paclitaxel in ovarian cancer patients pretreated with cisplatin/cyclophosphamide has demonstrated that topotecan is as effective as paclitaxel in the second-line treatment of these patients. Activity of topotecan was also observed in non-small-cell lung cancer, refractory leukemias/myelodysplastic syndromes and in childhood sarcomas. Due to its unique mechanism of action and lack of cross-resistance, cisplatin, etoposide, cytarabine and paclitaxel are potential interacting partners for combination chemotherapy regimens. However, the best combination regimen as well as the optimal combination schedule have yet to be conclusively determined. The potential of topotecan in a variety of solid tumors, as well as its use in combination regimens for ovarian and small cell lung cancer is currently being investigated.
A Phase II Study of Concomitant Chemoradiotherapy for Laryngeal Carcinoma Using Carboplatin
Authors: Nishioka Takeshi , Shirato Hiroki , Fukuda Satoshi , Arimoto Takuro , Kamada Tadashi , Furuta Yasushi , Nishino Shigeo , Hosokawa Yoichiro , Kitahara Toshihiro , Kagei Kenji , Inuyama Yukio , Miyasaka Kazuo
Published: April 2003

Purpose: We conducted a phase II study of concomitant chemoradiotherapy with carboplatin for laryngeal carcinoma. Materials and Methods: Sixty-four patients with stage II–IV (stage II, 36; III, 19; IV 9) laryngeal carcinoma were treated with concomitant administration of carboplatin (CBDCA) during radiotherapy (CRT group) between 1991 and 1994. There were 36 supraglottic, 25 glottic, and 3 subglottic carcinomas. Patients with stage II and stage III–IV received intravenous CBDCA of 100 mg/m2 and 120 mg/m2 once a week, respectively. Tumor response was assessed at 40 Gy in 16 fractions to select the patients suitable for total laryngectomy or radical radiotherapy of 65 Gy in 26 fractions in 6.5 weeks. The treatment results were compared with the historical control consisting of 56 patients consecutively treated from 1988 to 1990 without chemotherapy (RT group). The two studies were comparable with regard to patient characteristics, including age distribution, gender, tumor location, size, and clinical stage. Results: The actuarial 5-year survival rate was 80.3% for the CRT group and 81.3% for the RT group. A favorable response (complete response or partial response) at 40 Gy was observed in 87.5% of the patients of the CRT group and in 62.5% of the patients of the RT group (χ2 = 7.566, p < 0.01). The actuarial 5-year larynx preservation rate for the CRT group (75%) was significantly higher than that for the RT group (57%) in patients with T2 supraglottic carcinoma (p < 0.05). There was no difference in the larynx preservation rate between the two treatment arms for any T stage of glottic carcinomas. Conclusion: CRT using carboplatin improved the tumor response at 40 Gy and consequently achieved a higher larynx preservation rate for T2 supraglottic carcinoma. A clinical randomized trial is indicated to certify the findings of this phase II study.
Increased Serum Concentration of Circulating Soluble Receptor for Interleukin-2 and Its Effect as a Prognostic Indicator in Cachectic Patients with Gastric and Colorectal Cancer
Authors: Shibata Masahiko , Takekawa Motoo
Published: April 2003

Serum concentration of soluble interleukin-2 receptor (sIL-2R) was measured in noncachectic patients with 42 gastric and 32 colorectal cancers, 39 cachectic cancer patients and 15 normal volunteers. It increased with the advance of cancer, being highest in the cachectic patients. It was inversely correlated with the serum concentrations of nutriotional parameters such as prealbumin and transferrin, and positively correlated with the serum concentration of immunosuppressive acidic protein, soluble tumor necrosis factor receptor 1 and neopterin. The length of survival of cachectic patients (days) was inversely correlated also with the serum concentration of sIL-2R. These findings suggest that sIL-2R might be of use an important parameter to predict the progress of gastric and colorectal cancers, deterioration of the patients’ nutriotional status and immune activity as well as their prognosis.
Cyclin D3 Expression, Cell Proliferation and Pathological Stage of Human Primary Colorectal Cancer
Authors: Watson David Selby , Brotherick Ian , Shenton Brian Keith , Wilson Robert George , Angus Brian , Varma Jagmohan Singh , Campbell Frederick Charles
Published: April 2003

Cyclin D3 promotes cell cycle progression but its expression and prognostic significance in human colorectal cancer is unknown. This study assayed cyclin D3 expression against cell cycle phase fraction and Duke’s stage in 35 fresh human primary colorectal cancers. DNA content, cell cycle phase fraction and cyclin D3 expression were assessed by flow cytometry in disaggregated tumors. Cyclin D3 expression and S-phase fraction were independently related to Duke’s stage. In Duke’s stage C tumors, a higher proportion of cells expressed cyclin D3 (14.4 vs. 8.8%, mean; p < 0.05 by Mann-Whitney U test) and were in DNA synthesis (S) phase (21.1 vs. 9.7%, mean; p < 0.05 by Mann-Whitney U test). Neoplastic deregulation of cyclin D3 expression may provide a selective growth advantage which is related to stage in human colorectal cancer.
Complications of Subcutaneous Infusion Port in the General Oncology Population
Authors: Ballarini C. , Intra M. , Pisani Ceretti A. , Cordovana A. , Pagani M. , Farina G. , Perrone S. , Tomirotti M. , Scanni A. , Spina G.P.
Published: April 2003

Subcutaneous infusion ports (SIPs) represent a valid method for long-term chemotherapy. The SIPs have several advantages over other methods of venous access: they are easy to implant under local anaesthesia, have less discomfort for the patients, allow low costs, can be implanted in day hospital, and can be managed ambulatorily. However, SIPs have delayed complications, frequently related to clinical conditions of the neoplastic patients, and immediate complications, often due to the placement technique. From March 1992 to March 1997 we placed, under local anaesthesia and under fluoroscopic control, 102 SIPs in 99 general oncology patients for long-term chemotherapy (88% solid, 12% haematological tumours). The percutaneous venous access devices were in the subclavian vein in 96% of the cases and in the internal jugular vein in 4% of them. Immediate complications were: 1 haemopneumothorax, which required thoracic aspirations and two blood transfusions, 1 loop of the tunneled part of the catheter without alterations in SIP function, and 1 left jugular thrombosis in a patient with subclavian veins already thrombosed. The venous access was in the subclavian vein in the first 2 cases, and it was not necessary to suspend the therapeutic program. In the third instance, implanted in jugular vein, it was necessary to remove the SIP. Delayed complications were: 1 necrosis of the skin over the port, 1 infection of subcutaneous pocket, 2 infections of the system, 1 catheter deconnection, and 3 catheter ruptures with embolization of the catheter tip. The SIPs were removed in all cases but 1 in whom infection was successfully treated by appropriate antibiotic therapy. Embolization of the catheter required removal from the pulmonary artery under fluoroscopic guidance in the cardiac catheterization laboratory. In conclusion, infection and thrombosis are the two major complications of SIP in general oncology patients. In these cases it is not necessary to remove systematically the system, but a cor rect therapy (antibiotic, fibrinolytic agents) can be utilized with good results. The catheter rupture is often due to the wear over the costoclavicular angle. The interventional radiology is the method of choice in the treatment of the catheter embolization by rupture or dislocation. The experience of the surgical and nursing staff is probably the most important factor in decreasing the total rate of complications.
Intensified Adjuvant Cyclophosphamide, Methotrexate and 5-Fluorouracil Therapy: A Dose-Finding Study for Ambulatory Patients with Breast Cancer
Authors: Hietanen P. , Teerenhovi L. , Joensuu H.
Published: April 2003

Escalating doses of cyclophosphamide were given every 3 weeks as adjuvant treatment for women operated for breast cancer to determine the maximum tolerated dose of cyclophosphamide that can be given with constant doses of methotrexate (40 mg/m2) and 5-FU (600 mg/m2; CMF) as an outpatient treatment without the routine use of granulocyte colony-stimulating growth factor (G-CSF). The dose of cyclophosphamide was increased by 250 mg/m2 starting from the dose of 1,000 mg/m2. Mesna was given to prevent cystitis. The criteria for dose-limiting toxicity were grade IV granulocytopenia lasting for longer than 48 h, granulocytopenic infection or other grade IV toxicities. G-CSF and ofloxacin were used if grade IV granulocytopenia continued for longer than 48 h or if granulocytopenic infection occurred. At the dose level of 1,500 mg/m2 (500 mg/m2/week) 22 (92%) of the 24 patients had grade IV granulocytopenia during the 6 CMF cycles given, but only 3 (13%) had granulocytopenic fever. G-CSF was used in 28% of the cycles at this dose level. Other toxicities included complete alopecia (79%), nausea and vomiting. Sixteen (80%) of the premenopausal women became postmenopausal. At the dose level of 1,750 mg/m2 all 3 patients treated had to be hospitalized after the first cycle due to neutropenic infection (n = 2) or intractable vomiting even though prophylactic G-CSF was used. We conclude that intravenous CMF with a cyclophosphamide dose of 1,500 mg/m2 given at 3-week intervals with the selective use of prophylactic G-CSF is feasible as adjuvant treatment for patients with breast cancer.
Expression of DCC Protein in Colorectal Tumors and Its Relationship to Tumor Progression and Metastasis
Authors: Saito Mitsugu , Yamaguchi Akio , Goi Takanori , Tsuchiyama Tomokuni , Nakagawara Gizo , Urano Takeshi , Shiku Hiroshi , Furukawa Koichi
Published: April 2003

A loss of heterozygosity (LOH) at the DCC gene locus was detected in colorectal tumors, and this LOH might be related to metastasis. The aim of this study was to determine DCC protein expression in colorectal cancer and to evaluate its prognostic value. Allelic loss of the DCC locus was observed in 16 of the 23 patients (66.7%). In all 16 patients with LOH, DCC expression was decreased in the cancer tissue compared with the adjacent normal mucosa. All 23 colorectal tumors had decreased expression of this protein relative to the adjacent normal colonic mucosa in Western blot analysis. The levels of DCC protein were significantly lower in cancer tissues than in adenoma tissues. Decreased DCC protein expression was also observed by immunohistochemistry in the colorectal cancer cases. There were significant correlations between DCC protein expression and histologic type, venous invasion, and hematogenous metastasis. Patients with DCC-protein-negative tumors had a greater relative risk of recurrence compared with those whose tumors were DCC protein-positive. The 5-year survival rate was 91.0% in patients with DCC-protein-positive tumors, and 58.8% in those with DCC-protein-negative tumors; these differences between the two groups of patients were significant (p < 0.01). In multivariate analysis using the Cox regression model, DCC protein expression emerged as an independent prognostic indicator. These findings suggested that a decrease in DCC expression may have an important role in the progression of colorectal cancers and may be a biologic marker of prognostic significance.
Two Consecutive Phase II Studies of 5-Fluorouracil/Leucovorin/Mitomycin C and of Gemcitabine in Patients with Advanced Biliary Cancer
Authors: Raderer M. , Hejna M.H.L. , Valencak J.B. , Kornek G.V. , Weinländer G.S. , Bareck E. , Lenauer J. , Brodowicz T. , Lang F. , Scheithauer W.
Published: April 2003

Introduction: Carcinoma of the biliary system is a rare tumor entity, and patients with advanced disease face a dismal prognosis. Because of the absence of standard chemotherapy for advanced biliary carcinoma, we have performed two consecutive studies to evaluate the clinical potential of 5-fluorouracil, leucovorin and mitomycin C as well as the novel antimetabolite gemcitabine in this disease. Patients and Methods: A total of 39 consecutive patients suffering from locally inoperable or metastatic biliary cancer were enrolled in the study between March 1994 and October 1997. Twenty patients were treated with leucovorin 200 mg/m2 and 5-FU 400 mg/m2, both given as intravenous bolus on days 1–4, and mitomycin C 8 mg/m2 on day 1 (group A). Treatment cycles were repeated every 28 days. The second cohort included 19 patients, who received gemcitabine 1200 mg/m2 on days 1, 8 and 15 with a 2-week interval before the next treatment cycle (group B). Treatment was continued for a maximum of 6 cycles in the absence of progressive disease in both groups, and endpoints of the study were responses rates, survival and toxicity. Results: In group A, 5 patients (25%) had a partial response (PR), 6 additional patients (30%) had stable disease (SD) and 9 patients (45%) progressed during treatment. The median survival was 9.5 months (range, 3–14.5) with the median time to progression being 4 months (range, 3–9). In group B, 3 patients achieved a PR (16%), 4 showed SD (21%), while the remaining 12 patients had progressive disease. A median survival of 6.5 months (range, 2–11.5) was obtained, and the median time to progression was 2.5 months (range, 1–6+). Toxicity was generally mild in both treatment arms, 6 patients in group A required dose reductions, while no dose adaptation had to be performed for gemcitabine. Conclusion: Our data suggest that treatment of advanced biliary cancer is feasible and can be safely performed with both regimens applied in our study. While administration of gemcitabine has resulted in only mild toxicities, its exact impact on the management of advanced biliary cancer should be evaluated in a controlled trial.
Local Control after Curative Surgery for Cancer of the Extraperitoneal Rectum
Authors: Secco G.B. , Fardelli R. , Campora E. , Baldi E. , Bonfante P. , Ferraris R.
Published: April 2003

A retrospective study was carried out in 264 patients with low rectal cancer surgically treated with curative intent from January 1975 to December 1995 to analyze the influence of stapling devices on surgical and disease outcome. Patients were classified as follows: group 1 underwent surgery from 1975 to 1980, when staplers were not employed, and group 2 from 1981 to 1995, when stapling devices were routinely used. The use of stapling devices determined a corresponding increase in low anterior resection (LAR) and a decrease in postoperative mortality. A statistically significant difference in local recurrence rate between abdominoperineal resection (APR) patients and LAR sutured cases of group 1 was observed. In T3, N+ cases local recurrence rate was comparable in APR patients and LAR cases with stapled anastomosis. Improved local control occurred in stapled group 2 patients which was independent of the distal clearance. Although APR still plays an important role in treatment of lower rectal cancer, results indicated that a similar outcome after stapled LAR can also be expected in locally advanced carcinoma of the distal rectum, if accurate excision of perirectal tissue is carried out.
Chronological Changes in Incidences of Polymorphic Reticulosis in Korea and Japan
Authors: Ohsawa Masahiko , Shingu Norihisa , Inohara Hidenori , Kubo Takashi , Yang Woo-Ich , Yoon Joo-Hyeon , Aozasa Katsuyuki
Published: April 2003

Lethal midline granuloma (LMG) is a clinical term, which describes a group of diseases histologically comprising Wegener’s granulomatosis, polymorphic reticulosis (PR), and malignant lymphoma of the ordinary type (ML). PR is a variant of ML, and is considered to be a type of NK/T cell lymphoma. Our previous study revealed the clustering of patients with PR in East Asia including China, Korea and Japan. However, the frequency rate of PR varied even among these countries, with that of Korea being approximately 5 times higher than that of Japan. In the present study, we examined the incidences of each type of LMG, especially PR, in Korea (Yonsei University) and Japan (59 university hospitals) over time. A total of 102 cases and 655 cases of LMG admitted to Yonsei University, Korea from 1977 to 1996 and 59 university hospitals in Japan between 1965 and 1996, respectively, were examined. The frequency rate of PR per 100,000 outpatients of ears, nose and throat (ENT) clinics in Korea decreased from 40 to 20 between the periods of 1977–1989 and 1990–1996. However, there were no significant changes in Japan during the period studied.
Soluble CD44 Variant 6 as a Prognostic Indicator in Patients with Colorectal Cancer
Authors: Yamane Nariyuki , Tsujitani Shunichi , Makino Masato , Maeta Michio , Kaibara Nobuaki
Published: April 2003

The expression of CD44v6 is well known as a useful marker of tumor progression and prognosis in colorectal cancer. In this study, we evaluated the serum levels of soluble CD44 splice variants containing exon v6 (sCD44v6) and examined the histological expression of CD44v6 in patients with colorectal cancer. Serum samples were obtained from 44 primary colorectal cancer patients before surgery. We used enzyme-linked immunosorbent assay to determine the serum levels of sCD44v6. The expression of CD44v6 was examined by immunohistochemical staining of the primary tumors obtained from the same patients. Both the serum concentration of sCD44v6 and the expression of CD44v6 were significantly associated with lymph node metastasis (p < 0.05). Furthermore, the serum level of sCD44v6 was higher in those patients with CD44v6-positive tumor tissues (154.4 ± 34.8 ng/ml) than in those with CD44v6-negative ones (130.7 ± 32.3 ng/ml; p < 0.05). The 5-year survival rate was significantly lower in patients with high serum levels of sCD44v6 (52.4%) than in those with low levels of sCD44v6 (78.0%; p < 0.05), and it was also significantly lower in patients with CD44v6-positive cancer (42.1%) than in those with CD44v6-negative cancer (84%; p < 0.01). We concluded that preoperative elevation in the serum levels of sCD44v6 might be a prognostic indicator for patients with colorectal cancer.