bluuebunny/crossref_metadata_2025 huggingface dataset:
A Controlled Study for Gender Selection Using Swim-Up Separation
Authors: Khatamee Masood A. , Horn Scott R. , Weseley Alvin , Farooq Tahir , Jaffe Sharon B. , Jewelewicz Raphael
Published: April 2003

Objective: To evaluate the success for gender selection using a sample of semen separated by a modified swim-up technique. Design: We retrospectively compared the gender outcome of two treatments (A and B) for either a male or female offspring with those who conceived spontaneously. Setting: Private practice of one author (M.A.K.). Patients, Participants: The treatment groups consisted of 52 total pregnancies for couples who conceived by the separation technique. Of these 52 participants, 15 desired a female offspring and were placed into treatment A and 37 desired a male offspring and were placed into treatment B. The control groups consisted of 162 women who were presented with initial consultation for gender selection and conceived spontaneously. Control group A consisted of 80 women who initially chose a female offspring, and control group B consisted of 82 participants who initially chose a male. Interventions: In treatment group A, one timed intrauterine insemination (IUI) was carried out with the bottom 0.5 ml of the separated semen on cycle days 12–14, when the follicle was 18–22 mm. Patients in this group were also administered clomiphene citrate and human chorionic gonadotropin. In treatment group B, one timed IUI was done with the top 0.5 ml of the separated semen, when the follicle was 18–22 mm. Main Outcome Measure: The gender outcome of the pregnancies of two treatment and control groups was evaluated based on the known desired gender. Results: The success rate for conceiving a female child after intervention (treatment group A) was 86.7% effective (p = 0.002) as compared to the control group A. Couples seeking a male child (treatment group B) were 89.2% effective (p = 0.0002) as compared to the control group B. Conclusions: This study reveals that the modified swim-up method with additional monitoring results in statistically significant gender preselection.
Evaluation of Intrauterine Growth Pattern of Twins by Linear Discriminant Analysis of the Values of Biparietal Diameter, Femur Length and Abdominal Circumference1
Authors: Farina Antonio , Vesce Fortunato , Garutti Paola , Jorizzo Gianfranco , Bianciotto Andrea
Published: April 2003

In a cross-sectional study, the intrauterine growth pattern of 32 twins was compared to that of 205 singletons by analysis of the coefficients of the equations of biparietal diameter (BPD), femur length (FL) and abdominal circumference (AC). Lower values were observed in twins from the 20th week. BPD and AC curves showed a progressively diverging pattern, and yielded different coefficients of equations. AC showed the highest discriminant capacity followed by BPD and FL. Combined values of the two series solved by discriminant function output produced an overlapping of 58%. Based on our data, nomograms of growth of singletons should not be used for twins.
Regulation of Prostaglandin F2α by the Specific Inhibition of Secretory Type II Phospholipase A2: Implications for the Management of Premature Labour
Authors: Munns M.J. , King R.G. , Rice G.E.
Published: April 2003

Arachidonic acid mobilisation by phospholipase A2 (PLA2) and subsequent prostaglandin synthesis is thought to be a pivotal event in the onset and/or maintenance of human labour. The purpose of this study was to examine the efficacy of a monoclonal human type II PLA2 antibody (10 B2) in reducing prostaglandin F2α (PGF2α) production in Chinese hamster ovary (CHO) cells (that overexpress human recombinant type II PLA2) and in human placental explants. 10 B2 caused a concentration-dependent inhibition of PLA2 activity (p < 0.00001) and PGF2α release (p < 0.01) by CHO cells. 1 μM of 10 B2 inhibited PLA2 activity (p < 0.00001) and PGF2α production (p < 0.0001) in human placental explants. The latter effect was significantly reversed by the addition of arachidonic acid (30 μM; p < 0.01). On the basis of these findings, it is proposed that 10 B2 inhibits PGF2α production by interfering with the extracellular activity of type II PLA2.
Screening Sonohysterography in Infertility
Authors: Darwish Atef M. , Youssef Alaa A.
Published: April 2003

This prospective comparative study was carried out to assess the value of sonohysterography (SHG) in evaluating both the endometrial cavity and tubal patency in infertile patients and to compare its results with hysterosalpingography (HSG), diagnostic hysteroscopy and laparoscopic chromopertubation. It comprised 84 infertile women who were examined using SHG the day before combined diagnostic laparoscopy and hysteroscopy. Eighty-three patients had had HSG within 6 months. As regards the appearance of the endometrial cavity, the results of SHG agreed with hysteroscopy in 72.2% (k = 0.31) while HSG agreed with hysteroscopy in 75.6% (k = 0.39) of cases. The appearance of the right and left tubes using SHG agreed with laparoscopy in 72.4% (k = 0.16) and 60.5% (k = 0.13), respectively, while HSG agreed with laparoscopy in 94% (k = 0.52) and 90.4% (k = 0.51), respectively. However, when the appearance of fluid in DP was considered as an indirect indicator of patency of at least one tube at SHG, the agreement with laparoscopy rised to 88.1% (k = 0.24) and 85.7% (k = 0.18) for both tubes respectively. In conclusion, SHG is similar to HSG as regards the appearance of the endometrial cavity but it is inferior to it for evaluating tubal factor. The implication of SHG in the infertility work-up as a simple and fast procedure can minimize costs and abuses of sophisticated techniques particularly in the developing countries with limited resources.
Observations of High Iron Diamine-Alcian Blue Stain in Uterine Cervical Glandular Lesions
Authors: Kase Hiroaki , Kodama Shoji , Tanaka Kenichi
Published: April 2003

We studied epithelial glycoproteins in uterine cervical lesions, including glandular lesions, and investigated whether a more accurate diagnosis could be obtained using high iron diamine-alcian blue (HID-AB) stain and immunostaining with carcinoembryonic antigen (CEA). In addition, we examined the usefulness of preoperative diagnosis using biopsy specimens stained with HID-AB and CEA. Normal endocervical glands showed a predominance of sulfomucin, while adenocarcinoma predominantly showed sialomucin. CEA was highly detected in adenocarcinoma, but not in normal endocervix or in glandular dysplasia, suggesting that this stain has high specificity. The staining patterns of biopsy specimens and hysterectomy specimens were similar. Therefore HID-AB stain and CEA stain may be useful as a supplementary means of diagnosing uterine cervical lesions.
Krukenberg Tumors:Can Management Be Improved? 1
Authors: McGill Frances M. , Ritter Diane B. , Rickard Caroline S. , Kaleya Ronald N. , Wadler Scott , Greston Wilma Markus , O’Hanlan Katherine A.
Published: April 2003

Objective: The Montefiore Medical Center experience with women with gastrointestinal (GI) cancer was reviewed to: (1) evaluate clinical parameters in patients with Krukenberg tumor (GI cancer metastatic to the ovaries) and (2) evaluate oophorectomy in GI cancer patients. Methods: (1) Charts of all female patients admitted between 1985 and 1996 with gastric or colon cancer were reviewed. Results: The frequency of Krukenberg tumor was 7/1,021 (0.7%). The median age at presentation was 39.5 years (range 35–80); 5 were premenopausal, 2 of whom were postpartum. Krukenberg tumor was significantly more common in the premenopausal patients with gastric cancer (p = 0.002), colon cancer (p = 0.001), and in both sites combined (p < 0.001). Our rate of pregnancy-associated Krukenberg tumors (28.6%) was significantly higher (p < 0.05) than that found in 4 of 5 large studies. The average survival of our 7 patients was 12.3 months (range 4 days to 26 months), with secondary debulking and chemotherapy offering 1 patient the longest longevity. Only 19/788 (2.4%) women had oophorectomy during their colon cancer surgery revealing 2 (10.5%) Krukenberg tumors, 6 (31.6%) benign solid or cystic ovarian tumors, and 11 (57.9%) normal or atrophic ovaries. Conclusions: Krukenberg tumors are rare. There is no uniformity of data reported in the literature. Krukenberg tumors were more common in premenopausal women with gastric or colon cancer compared to postmenopausal women. Our rate of pregnancy-associated Krukenberg tumors appeared to be higher compared to other studies. Prophylactic oophorectomy in pre- and postmenopausal women should be considered at the time of GI cancer surgery, and requires further study. A national registry combined with prospective, multisite studies are needed to gather data and evaluate treatment.
Prenatal Diagnosis of Nonmosaic Trisomy 9 in a Fetus with Severe Renal Disease
Authors: Sandoval R. , Sepulveda W. , Gutierrez J. , Be C. , Altieri E.
Published: April 2003

We report a case of nonmosaic trisomy 9 presenting at 21 weeks of gestation with polycystic, echogenic horseshoe kidney, collapsed bladder, absent amniotic fluid, and intrauterine growth restriction. Color Doppler imaging demonstrated no blood flow signals from renal vessels. Fetal blood sampling confirmed a 47,XX,+9 karyotype, with no evidence of mosaicism, and increased serum β2-microglobulin levels of 10.7 mg/l, consistent with severe renal failure. A repeat scan at 23 weeks also revealed a dysmorphic face, bilateral microphthalmia, and a cerebellar vermian defect. Follow-up examinations showed progressive growth restriction leading to fetal death at 33 weeks of gestation. This report demonstrates that fetuses with nonmosaic trisomy 9 may present with severe renal abnormalities and confirms that cases seen in the second and third trimesters usually have a dismal outcome.
Endometrioid Adenocarcinoma Arising from Adenomyosis
Authors: Takai Noriyuki , Akizuki Shin’ichiro , Nasu Kaei , Etoh Yasuko , Miyakawa Isao
Published: April 2003

In spite of many references to carcinoma arising from endometriosis at extrauterine sites, there are few documented cases of carcinoma developing in association with adenomyosis. We present 2 rare cases of adenocarcinoma arising from adenomyosis. The relationship between prior frequent estrogen use and carcinogenesis and the possible effects of chemotherapy and radiation therapy are reviewed.
Elevated Second-Trimester Serum Homocyst(e)ine Levels and Subsequent Risk of Preeclampsia
Authors: Sorensen Tanya K. , Malinow M. Rene , Williams Michelle A. , King Irena B. , Luthy David A.
Published: April 2003

Objective: Elevated plasma homocyst(e)ine is a risk factor for endothelial dysfunction and vascular disease. In late gestation, levels of homocyst(e)ine are higher in preeclamptics, as compared with normotensive pregnant women. Our objective was to determine whether homocyst(e)ine elevations precede the development of preeclampsia. Study Design: We used a prospective nested case-control study design to compare second trimester maternal serum homocyst(e)ine concentrations in 52 patients who developed preeclampsia (pregnancy-induced hypertension with proteinuria) compared with 56 women who remained normotensive throughout pregnancy. Study subjects were selected from a base population of 3,042 women who provided blood samples at an average gestational age of 16 weeks and later delivered at our center. Serum homocyst(e)ine was measured by high-performance liquid chromatography and electrochemical detection. Results: Approximately 29% of preeclamptics, as compared to 13% of controls had homocyst(e)ine levels ≥5.5 μmol/l (upper decile of distribution of control values). Adjusted for maternal age, parity, and body mass-index, a second trimester elevation of homocyst(e)ine was associated with a 3.2-fold increased risk of preeclampsia (adjusted OR = 3.2; 95% CI 1.1–9.2; p = 0.030). There was evidence of a interaction between maternal adiposity (as indicated by her prepregnancy body mass index) and parity with second trimester elevations in serum homocyst(e)ine. Nulliparous women with elevated homocyst(e)ine levels experienced a 9.7-fold increased risk of preeclampsia as compared with multiparous women without homocyst(e)ine elevations (95% CI 2.1–14.1; p = 0.003). Women with a higher prepregnancy body mass index (≥21.4 kg/m2, or upper 50th percentile) and who also had elevated homocyst(e)ine levels, as compared with leaner women without homocyst(e)ine elevations were 6.9 times more likely to later develop preeclampsia (95% CI 1.4–32.1; p = 0.016). Conclusion: Our findings are consistent with other indications of vascular endothelial dysfunction predating clinical preeclampsia. Studies designed to examine the effect of dietary and/or pharmacological mediators of homocyst(e)ine metabolism in preeclampsia are warranted.
The Chick Embryo Chorioallantoic Membrane as a Model to Investigate the Angiogenic Properties of Human Endometrium
Authors: Maas Jacques W.M. , Le Noble Ferdinand A.C. , Dunselman Gerard A.J. , de Goeij Anton F.P.M. , Struyker Boudier Harry A.J. , Evers Johannes L.H.
Published: April 2003

The chick embryo chorioallantoic membrane (CAM) is an established in vivo angiogenesis assay. The aim of our study was to assess the angiogenic properties of endometrium and to quantitate the vascular response in an accurate way. Samples of proliferative endometrium (n = 17) and control mouse skin tissue (n = 8) were explanted onto the CAM at day 10 of incubation. Additional controls consisted of normal unmanipulated CAM (n = 12). Four days after grafting, photographs of the explant and the surrounding area were taken in ovo to measure the vascular density index (VDI). The VDI is a stereological estimate of vessel number and length, which was obtained by counting the intersections of vessels with a circular grid superimposed on a computerized image. Endometrium caused a significant increase in VDI as compared to both unmanipulated CAM (p < 0.001) and skin tissue as a control (p < 0.007). The intra-observer variability was 5.2%. This study demonstrates that the CAM assay is a suitable model to assess the angiogenic properties of endometrium. Furthermore, it allows detailed quantitation of the vascular response in an objective and reproducible way. Our findings suggest the CAM to be a promising model to study the role of angiogenesis in both normal human endometrium and diseases involving the endometrium.
Effect of Ovarian Involvement on the Frequency of Luteinized Unruptured Follicle in Endometriosis
Authors: Kaya Hakan , Oral Baha
Published: April 2003

Objective: When we review the current literature on endometriosis and luteinized unruptured follicle (LUF), we see that most of the studies deal with only the association between LUF frequency and the severity of endometriosis. Our purpose was to evaluate the effect of ovarian involvement on LUF frequency in endometriosis and assess the relationship between endometriosis and LUF in infertile women. Study Design: This study is a prospective analysis covering a total of 126 infertile women between 22 and 35 years of age who underwent diagnostic laparoscopy from September 1995 to August 1997 in the Department of Obstetrics and Gynecology at Süleyman Demirel University, Isparta, Turkey. Endometriosis was diagnosed in 58 of these patients. All had received a revised American Fertility Society staging score at the time of the laparoscopic diagnosis. Diagnosis of LUF was made when the following criteria were fulfilled: absence of ultrasonic signs of ovulation, and absence of an ovulation ostium on the follicle by laparoscopy, despite increased serum progesterone. Statistical evaluation was performed using χ2 test and Fisher’s exact test where appropriate. Results: The prevalence of LUF in mild, moderate and severe endometriosis cases was 13.3, 41.2 and 72.7%, respectively. The LUF frequencies were 45.9% in 37 endometriosis patients with ovarian involvement, 9.5% in 21 cases without ovarian involvement, and 5.9% in 68 cases without endometriosis. A statistically significant difference was observed between the LUF rate in the group with ovarian involvement and that without involvement (χ2 = 8.06, p < 0.001). Conclusion: In summary, in this study we noted a significant increase in LUF frequency in endometriosis patients with ovarian involvement.
Use of Chlorhexidine-Releasing Nylon Fibres to Reduce Device-Related Uterine Infections
Authors: Gard P.R. , Reynolds J.P. , Hanlon G.W.
Published: April 2003

Implantation of intrauterine devices (IUDs) is associated with an increased incidence of uterine infection, probably as a result of vaginal bacteria entering the uterus at the time of insertion. To reduce the incidence of IUD-related infections, the incorporation of antimicrobial agents into the tail of the device was studied. Chlorhexidine was shown to be released from within nylon hollow fibres at a rate of approximately 114 μg·day–1 for 10 days. This rate of release was sufficient to exhibit a biocidal effect on bacteria embedded within a mucus gel in vitro. When these devices were implanted transcervically into the guinea-pig uterus they significantly reduced the extent of uterine bacterial contamination within 24 h. These findings indicate that chlorhexidine-releasing devices are potentially useful in the reduction of device-related infections.
Lipid Peroxidation in Pregnancy with Preeclampsia and Diabetes
Authors: Kharb Simmi
Published: April 2003

We studied lipid peroxidation and vitamin E levels in 12 diabetic preeclamptic, 13 nondiabetic preeclamptic, 8 gestational diabetic, 25 normotensive pregnant women, and 25 healthy nonpregnant women. A significant increase in malonaldehyde (MDA) levels was observed in preeclamptic and diabetic preeclamptic women as compared to normotensive pregnant and healthy controls (p < 0.001). An increase in MDA levels was observed in gestational diabetics, but the difference was not statistically significant. Likewise, a significant fall in vitamin E levels was noted in preeclamptic and diabetic preeclamptic groups as compared to controls (p < 0.001). Gestational diabetics had a slight decrease in vitamin E levels relative to controls. These findings suggest that lipid peroxidation plays a role in the pathogenesis of preeclampsia.
Effects of a Vasopressin Antagonist in Women with Dysmenorrhea
Authors: Valentin Lil , Sladkevicius Povilas , Kindahl Hans , Broeders Anja , Marsal Karel , Melin Per
Published: April 2003

We compared menstrual pain, uterine contractility and blood circulation, and plasma concentrations of vasopressin and prostaglandin F2α metabolite in women with versus without primary dysmenorrhea, and determined the effects of a vasopressin antagonist, 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-oxytocin (Atosiban), on these parameters. Our results do not support the contention that vasopressin is involved in the etiology of dysmenorrhea, plasma concentrations of vasopressin being similar in dysmenorrheic women and controls, and the vasopressin antagonist Atosiban having no effect on menstrual pain, intrauterine pressure or uterine artery pulsatility index in dysmenorrheic women.
Treatment of High-Grade Gliomas in the Elderly
Authors: Brandes Alba , Fiorentino Mario V.
Published: April 2003

In recent years the elderly population has grown, and in this category there has been a marked increase in the incidence of cancers with a poor prognosis, brain tumors in particular. However, few authors have focused on treatment for high-grade gliomas in the elderly, which often present problems different from those in younger populations. Several authors have observed that this tumor has a poor response to surgery, radiotherapy and chemotherapy. Elderly patients are therefore frequently undertreated or excluded from cancer therapy trials. Their exclusion from conventional cancer treatment often depends on ad hoc decisions and assumptions by physicians rather than on sound scientific data.
Association between Helicobacter pylori Infection and Pancreatic Cancer
Authors: Raderer Markus , Wrba Friedrich , Kornek Gabriela , Maca Thomas , Koller Dieter Y. , Weinlaender Georg , Hejna Michael , Scheithauer Werner
Published: April 2003

Purpose: In order to determine whether infection with Helicobacter pylori might be associated with pancreatic adenocarcinoma, we performed a study to compare the H. pylori seroprevalence rate between patients with pancreatic carcinoma and matched control subjects. Patients and Methods: Blood samples from 92 patients with histologically confirmed diagnosis of pancreatic adenocarcinoma admitted to our hospital between January 1994 and July 1995 were analyzed for the presence of IgG antibodies against H. pylori by a commercially available enzyme-linked immunosorbent assay. Thirty patients with gastric cancer, 35 patients with colorectal cancer, and 27 healthy volunteers served as controls. In addition to these serological analyses, tumor specimens from 20 patients with pancreatic adenocarcinoma were microscopically investigated for the presence of H. pylori. Results: 65% of pancreatic cancer patients and 69% of those with gastric cancer were found to be seropositive, while only 45% of the other controls tested positive. Statistical analysis revealed no difference in seropositivity between the cohort of patients suffering from pancreatic and gastric cancer. The rate of seropositivity was more prominent, however, in pancreatic cancer patients when compared with those suffering from colorectal cancer combined with normal controls (p = 0.035), with an odds ratio of 2.1 (1.1–4.1). Microscopic evaluation of human pancreatic cancer specimens showed no evidence for the presence of H. pylori. Conclusion: Our data suggest an association between H. pylori infection and pancreatic cancer. Despite demonstration of a positive relationship and its physiological plausibility, larger prospective studies are needed to confirm our preliminary findings and to assess H. pylori as a potential carcinogenic risk factor.
Clinical Pilot Study of Intrahepatic Arterial Chemotherapy with Methotrexate, 5-Fluorouracil, Cisplatin and Subcutaneous Interferon-Alpha-2b for Patients with Locally Advanced Hepatocellular Carcinoma
Authors: Urabe Takeshi , Kaneko Shuichi , Matsushita Eiki , Unoura Masashi , Kobayashi Kenichi
Published: April 2003

To evaluate the efficacy of methotrexate (MTX)-5-fluorouracil (5-FU), cisplatin (CDDP), and interferon-α-2b(IFNα-2b) combination therapy, we conducted a clinical pilot study in patients with locally advanced hepatocellular carcinoma (HCC). Sixteen patients, who had received no prior treatment for the HCC, with portal tumor thrombosis in the main trunk or in the major branch were enrolled in the study. IFNα-2b (3 × 106 units) was injected subcutaneously 3 times per week. After a bolus administration of MTX (30 mg/m2), CDDP (75 mg/m2) and thereafter 5-FU (750 mg/m2) were given weekly by intrahepatic arterial infusion. In 15 eligible patients, there were 1 complete response (CR) and 6 partial responses (PR) with a response rate of 46.7%. Median survival of the 15 patients was 7 months, and the 2-year survival rate of CR and PR patients was 57.1%. There was severe transient hematologic toxicity. More than grade 2 nausea/vomiting was noted in >50%. In conclusion, the IFNα-2b combination chemotherapy demonstrated good response in patients with locally advanced HCC. This treatment should be tried in a controlled study.
Subcutaneous Low Doses of Interleukin-2 and Recombinant Interferon Alpha with Carboplatin and Vinblastine in Patients with Advanced Melanoma1
Authors: Bafaloukos D. , Fountzilas G. , Skarlos D. , Pavlidis N. , Bakoyiannis C. , Karvounis N. , Kosmidis P.
Published: April 2003

Twenty-three patients with advanced melanoma were treated with a combination of subcutaneous recombinant human interleukin-2 (IL-2), and recombinant interferon alpha-2a (IFN-α) with chemotherapy consisting of four cycles of carboplatin (300 mg/m2, day 1) and vinblastine (6 mg/m2, day 1), every 28 days (CV-IL-IF). IL-2 was given at a dose of 4.5 × 106 U twice daily on days 3–6 and days 21–24 of each cycle; IFN-α dose was 4.5 × 106 U, starting on day 2, thrice weekly. Immunotherapy was intended to continue for 6 months. Of the 23 analyzed patients, 4 (17%) achieved an objective response, including 1 complete and 3 partial responses, in nonvisceral metastatic disease. The median time to progression was 5 months and the median survival from onset of the treatment 6 months (range 1–14 months). Four patients discontinued the treatment, due to nonhaematologic toxicity; 3 for severe weakness and the 4th patient for long-lasting CNS side-effects. Other grade 3–4 toxicities included weight loss (22%), nausea and vomiting (17%) and alopecia (13%). The haematologic toxicity was acceptable. No toxic death was noted. It is con cluded that the CV-IL-IF regimen has limited activity and moderate toxicity.
Molecular Genetics and Clinical-Pathology Features of Hereditary Nonpolyposis Colorectal Carcinoma (Lynch Syndrome)
Authors: Lynch Henry T. , Smyrk Thomas , Lynch Jane F.
Published: April 2003

Hereditary nonpolyposis colorectal cancer (HNPCC), also termed Lynch syndrome, was originally called cancer family syndrome. Historically, in 1913 Aldred Warthin, a pathologist, published a family, now known as Family G, which had features of HNPCC. It was first delineated as a hereditary cancer syndrome in the mid-1960s by Lynch. There was an apparent autosomal dominant mode of inheritance of colorectal cancer and certain integral cancers, the most prominent of which was endometrial carcinoma. Prior to the discovery in 1993 and 1994 of genes (hMSH2, hMLH1, hPMS1, hPMS2) known as mismatch repair genes or mutator genes, the diagnosis of HNPCC rested exclusively upon evaluation of clinical findings in concert with a well-documented and extended pedigree. Thus, this disorder has evolved from a medical curiosity into a clinical syndrome wherein molecular biologists provided proof of its hereditary status. These discoveries should aid in elucidating its pathogenesis and carcinogenesis and in the next decade we likely will learn more about chemoprevention and surgical prophylaxis of HNPCC.
Prognostic Relevance of MMP-2 (72-kD Collagenase IV) in Gastric Cancer
Authors: Allgayer Heike , Babic Rudolf , Beyer Bianca C.M. , Grützner Klaus Uwe , Tarabichi Anwar , Schildberg Friedrich Wilhelm , Heiss Markus Maria
Published: April 2003

The association of MMP-2 (matrix metalloproteinase 2, 72-kD collagenase IV) with invasive and metastatic capacity of tumor cells has implicated a potential role in the prognosis for cancer patients. However, no larger study has been done to prove this hypothesis. The present study was therefore designed to investigate the prognostic impact of MMP-2 in a prospective series of 203 gastric cancer patients. MMP-2 expression was measured immunohistochemically and scored semiquantitatively (score 0–3) in carcinoma cells, and results were correlated with clinicopathological tumor parameters and parameters of the urokinase-type plasminogen activator (uPA) system. Survival analyses were done using the Kaplan-Meier method (log-rank statistics) and multivariate Cox analysis. Significant correlations were found for MMP-2 and Laurén’s classification, M stage and proteases/inhibitors of the uPA system in the primary tumor. Kaplan-Meier analysis revealed an association of increasing MMP-2 expression with worse prognosis. This was especially seen in patients with a parallel high expression of uPA receptor. However, differences in survival probabilities between low and high MMP-2 levels were not significant. In a separate analysis of diffuse-type cancers, MMP-2 was significantly associated with disease-free (p = 0.0056) and overall survival (p = 0.0426). Multivariately, MMP-2 was not an independent parameter. Our results demonstrate that there is an association of immunohistochemical detection of MMP-2 with prognosis of cancer patients. For diffuse gastric cancers, it is a significant prognostic parameter, however, not of independent impact. The study further suggests that consideration of interrelated tumor-associated proteases like uPA receptor in combination with MMP-2 may improve its prognostic power.
Expression of Insulin-Like Growth Factor-2 Can Predict the Prognosis of Human Colorectal Cancer Patients: Correlation with Tumor Progression, Proliferative Activity and Survival
Authors: Kawamoto Kazuyuki , Onodera Hisashi , Kondo Shohei , Kan Shugen , Ikeuchi Daisuke , Maetani Shunzo , Imamura Masayuki
Published: April 2003

Expression of insulin-like growth factor-2 (IGF-2) has been reported in tissue specimens and cell lines of human colorectal cancers. However, the effects of IGF-2 in colorectal cancer patients are not well known. In this study, IGF-2 staining was performed on tissue samples from 92 patients with colorectal cancer, and the relationship of IGF-2 staining to clinicopathological variables, proliferating cell nuclear antigen (PCNA) staining and patient survival was analyzed. IGF-2 staining was correlated with tumor progression, PCNA staining and patient survival. Our results suggest that IGF-2 plays an important role in tumor progression and that IGF-2 staining is useful as a prognostic factor in colorectal cancer patients.
Prognosis and Management Strategies of Lymphatic Neoplasias in the Elderly
Authors: Greil Richard
Published: April 2003

In Caucasians, Hodgkin’s disease demonstrates constant incidence rates, with a first peak occurring in adolescents and in young adults, and a second peak in the elderly. Age is an important risk factor for overall survival of patients; staging strategies and treatment expose elderly patients to an even higher risk arising from surgical complications, death from secondary cancer and leukemia or lethal cardiac complications. In contrast to non-Hodgkin’s lymphoma, optimal staging and treatment procedures have not yet been defined for this disease in elderly patients. However, due to the very poor prognosis of inadequately treated patients, treatment recommendations at present must be based on those for younger patients while keeping the individual risk profile in mind. If staging laparotomy is omitted, most patients will require a combined modality treatment. While in low-risk patients a reduced number of cycles with full-dose chemotherapy like ABVD (Adriblastina, bleomycin, vinblastine, dacarbazine) or of six cycles with less toxic drugs like VBM (vinblastine, bleomycin, methotrexate) followed by limited field radiotherapy may suffice, patients with well-defined risk factors will require a more prolonged chemotherapy. Currently, there is no evidence that C(M)OPP [cyclophosphamide (mustargen), vincristine, procarbazine, prednisone]/ABVD or ABVD may successfully be replaced by less toxic regimens. Therefore, further studies are required on the specific definition of biological age, the cost/benefit ratio of staging procedures and treatment and the influence of these strategies on the quality of life in the elderly.
Is Continuous 24-Hour Infusion of 5-Fluorouracil plus High-Dose Folinic Acid Effective in Patients with Progressive or Recurrent Colorectal Cancer?
Authors: Hartmann J.T. , Köhne C.-H. , Schmoll H.-J. , Daikeler T. , Kanz L. , Bokemeyer C.
Published: April 2003

Background: To evaluate the therapeutic activity of 24-hour continuously infused 5-fluorouracil (5-FU) modulated by high-dose folinic acid in patients with metastatic colorectal cancer who had recurred or progressed following mainly bolus 5-FU/folinic acid chemotherapy. Patients and Methods: Forty-two patients with a median age of 59 years (45–76) were enrolled. Karnosfky status was 90% (80–100), previous chemotherapy regimen bolus 5-FU/folinic acid (n = 33, 79%) or 24-hour continuous 5-FU ± interferon α2 (n = 9, 21%). Chemotherapy was given as a weekly infusion of 500 mg/m2 folinic acid over 2 h followed by a 24-hour continuous infusion of 2,600 mg/m2 5-FU for 6 consecutive weeks followed by a 2-week rest period. Results: No complete but 6 partial responses were observed (ORR: 14%, CI95%: 3.5–25.1%) with a median response duration of 7.3 months (range: 1.4–10.6). The median survival from the start of continuous infusion of 5-FU was 11.6 months (range: 2–27, CI95%: 9.4–13.8) and the 1-year survival rate was 46%. Disease stabilization and minor responses were achieved in another 25 patients (61%). WHO grade III/IV diarrhea occurred in 26% of patients, mucositis, nausea/vomiting and hand-foot syndrome in 5% each. Two cases of WHO grade III anemia and leukocytopenia were observed (5% each). Dose reductions had to be performed in 11 patients because of unacceptable diarrhea with subsequent stop of treatment in 2 patients. Progressive disease while receiving previous bolus 5-FU chemotherapy was associated with a lower response rate, shorter progression-free interval and overall survival compared to response and survival of patients who had achieved temporary disease stabilization during previous bolus 5-FU therapy. Conclusions: Continuous infusion of 5-FU/folinic acid displays activity in pretreated and refractory colorectal cancer with acceptable toxicity. Patients who had achieved disease stabilization or objective remission with previous 5-FU bolus therapy appear to be more likely to benefit from second-line treatment. Questions remaining to be addressed include the optimal starting dose of continuously infused 5-FU and whether the dose of folinic acid can be reduced or completely eliminated with respect to toxicity and health economics.
Combined Expression of HLA-DR Antigen and Proliferating Cell Nuclear Antigen Correlate with Colorectal Cancer Prognosis
Authors: Kunihiro Masaki , Tanaka Shinji , Haruma Ken , Yoshihara Masaharu , Sumii Koji , Kajiyama Goro , Shimamoto Fumio
Published: April 2003

HLA-DR antigen expression and the proliferating cell nuclear antigen labeling index (PCNA-LI) were examined immmunohistochemically in 59 surgically resected advanced colorectal cancers to clarify the clinicopathologic significance of the HLA-DR antigen. HLA-DR antigen expression was detected in 33 (56%) of the 59 lesions, which showed less frequent liver metastasis than lesions without HLA-DR antigen expression (40 vs. 68%; p < 0.05). Five-year survival rates of patients with and without HLA-DR antigen expression were 50 and 19%, respectively. Lesions combining HLA-DR antigen expression and a relatively low PCNA-LI had the best prognosis. These results indicate that HLA-DR antigen expression, particularly combined with a low PCNA-LI, is an important outcome predictor in colorectal cancer.
Effects of Doxorubicin and/or Cilostazol on Cancer Cells during Liver Regeneration after Two-Thirds Hepatectomy in Rats
Authors: Ikeda Yasuharu , Matsumata Takashi , Takenaka Kenji , Yamagata Motoyuki , Sugimachi Keizo
Published: April 2003

A rat model of liver metastases generated by intraportal injection of syngeneic tumor cells after two-thirds hepatectomy to determine the optimal benefit of doxorubicin and/or cilostazol for early hepatic metastases. Four groups of WKA rats had viable tumor cells injected directly into the portal vein after two-thirds hepatectomy. Group A underwent to further treatment. Group B had doxorubicin injected 24 h post-operatively. Group C had cilostazol administered prior to two-thirds hepatectomy. Group D received cilostazol, and doxorubicin injections. The mean survival period in each group was 22.2, 20.0, 28.8, and 22.8 days, respectively. The mean survival was significantly longer in group C than in groups A, B and D (p < 0.05). Based on these findings, we believe that during the phase of liver regeneration adjuvant chemotherapy is not recommended. Cilostazol exerts an important antiproliferative effect on liver metastases after hepatectomy.
First-Line Vinorelbine-Mitoxantrone Combination in Metastatic Breast Cancer Patients Relapsing after an Adjuvant Anthracycline Regimen: Results of a Phase II Study
Authors: Llombart-Cussac Antonio , Pivot Xavier , Rhor-Alvarado Alba , Le Cesne Axel , Le Chevalier Thierry , Tursz Thomas , Spielmann Marc
Published: April 2003

Purpose: Previous studies demonstrated that doxorubicin and vinorelbine combinations in first-line chemotherapy are highly active in metastatic breast cancer. Mitoxantrone is an anthracenedione with low cardiotoxicity, and seems to be effective when combined with vinorelbine after prior exposure to anthracyclines. Patients and Methods: Seventy-two patients with metastatic breast cancer were included in a phase II study. All patients had previously received one anthracycline-containing regimen (doxorubicin or epirubicin) in an adjuvant setting. Vinorelbine was administered at 25 mg/m2 in a 20-min intravenous (i.v.) infusion, days 1 and 8. Mitoxantrone was given at 10 mg/m2 (66 patients) or 12 mg/m2 (6 patients) in a slow i.v. infusion on day 1. Courses were repeated every 3 weeks. Results: Sixty-five patients were evaluable for response; the objective response rate was 49% (95% CI: 37–63%), including four complete and 28 partial responses, with a median duration of response of 7 months (range 2.3–27). Median overall survival was 19 months (range 2–48). Grade 3–4 granulocytopenia was observed in 46% of patients. There were 12 admissions (3% of cycles), involving 17% of patients for febrile neutropenia. Seven patients (10%) experienced grade 3 or 4 cardiotoxicity, and 1 patient died of cardiac heart failure. Other side effects were rare and mild. Conclusions: The vinorelbine and mitoxantrone combination is an active regimen with low toxic complications when cumulative doses of mitoxantrone are limited to 70 mg/m2. The results in this phase II study make it worthwhile including this regimen in a phase III study for patients who have previously received an anthracycline-containing regimen.
Allelic Loss and Microsatellite Instability in Prostate Cancers in Japan
Authors: Watanabe Masatoshi , Shiraishi Taizo , Muneyuki Tsuyoshi , Nagai Moritaka , Fukutome Kazuo , Murata Mariko , Kawamura Jyuichi , Yatani Ryuichi
Published: April 2003

A series of 25 primary prostate cancers in Japanese were screened for loss of heterozygosity and microsatellite instability using twelve microsatellite markers containing APC, DCC, TP53, BRCA1, and BRCA2. Frequent loss of heterozygosity was observed for D8S201 (48%), LPL (48%), and DCC (26%). In contrast, the incidence did not exceed 15% at BRCA1 and BRCA2 loci. Microsatellite instability was observed in 28% of stage B, C, and D cancers. These data suggest that microsatellite instability and loss of unidentified genes on chromosome 8p may be involved in carcinogenesis of the prostate; however, BRCA1 and BRCA2 may not be largely involved in the development of prostate cancer in the Japanese population.
Expression of p53 and Vascular Endothelial Growth Factor Associated with Tumor Angiogenesis and Prognosis in Gastric Cancer
Authors: Maeda Kiyoshi , Kang Soon-Myoung , Onoda Naoyoshi , Ogawa Masafumi , Sawada Tetsuji , Nakata Bunzo , Kato Yasuyuki , Chung Yong-Suk , Sowa Michio
Published: April 2003

Recently, it has been reported that p53 tumor suppressor gene plays an important role in controlling tumor angiogenesis by regulating expression of vascular endothelial growth factor (VEGF), which is a well-characterized angiogenic inducer. In this study, we investigated these antigens’ expression together with microvessel density, and investigated their clinical importance. One hundred twenty specimens resected from patients with gastric carcinoma were investigated using immunohistochemical methods. p53 and VEGF expression was observed in 42 and 35% tumors, respectively. p53 and VEGF staining status was coincided in 72% tumors, and a significant correlation was found between p53 and VEGF status. The microvessel density, determined by immunostaining for factor VIII-related antigen, was significantly higher in p53-positive or VEGF-positive tumors. According to prognosis, patients with p53-positive tumors had significantly worse survival than those with p53-negative tumors. There was also a significant worse survival in the patients with VEGF-positive tumors than those with VEGF-negative tumors. Moreover, the 5-year survival rate was lowest in the patients with p53-positive and VEGF-positive tumors, while it was highest in the patients with p53-negative and VEGF-negative tumors. In conclusion, both p53 and VEGF significantly correlated with tumor vascularity and prognosis in patients with gastric carcinoma.
Mutations and Amplification of Oncogenes in Endometrial Cancer
Authors: Niederacher Dieter , An Han-Xiang , Cho Yong-Jig , Hantschmann Peer , Bender Hans G. , Beckmann Matthias W.
Published: April 2003

Alterations in oncogenes are critical steps in the development of endometrial cancer. To investigate the potential clinical relevance of the amplification of the oncogenes c-erbB2, c-myc, and int-2 and the mutation of K-ras in endometrial cancer, 112 tumors were examined using PCR-based fluorescent DNA technology. Amplification of the three oncogenes and the mutation of K-ras were correlated with age, tumor size, lymph node status, metastases, stage, histological types, grade, steroid hormone receptor expression (estrogen receptor, ER; progesterone receptor, PgR), family history of cancer, previous history of cancer or precursor lesions, and previous history of hormone replacement therapy. Oncogene amplification of c-erbB2 was detected in 18.9%, of c-myc in 2.7% and of int-2 in 4.2%, and K-ras mutation in 11.6%. No significant correlations could be detected between amplification of c-erbB2 and any of the other parameters. Mutation of K-ras is associated with positive expression of PgR. This might indicate that mutation and activation of K-ras are involved in the development of hormonal independence in endometrial cancer.
Detection and Clinical Correlations of ras Gene Mutations in Human Ovarian Tumors
Authors: Varras Michael N. , Sourvinos George , Diakomanolis Emmanouel , Koumantakis Eugenios , Flouris GeorgeA. , Lekka-Katsouli Joanna , Michalas Stylianos , Spandidos DemetriosA.
Published: April 2003

In epithelial ovarian neoplasms K-ras codon 12 gene mutations show a wide variation fluctuating between 4–39% in invasive carcinomas and 20–48% in borderline malignant tumors. In this study, we showed the pattern of point mutations in codon 12 of the K-ras, H-ras and N-ras genes, using polymerase chain reaction restriction fragment length polymorphism analysis in 74 tissue specimens of Greek patients with epithelial ovarian tumors. K-ras and H-ras gene mutations were detected in 11/48 (23%) and 3/48 (6%) cases with primary invasive ovarian carcinomas, respectively, while N-ras gene mutations were not found. No mutation of K-, H- and N-ras genes was detected in 23 ovarian cystadenomas. In 1 out of 3 borderline ovarian tumors (33%) we found an H-ras gene mutation. The prevalence of mutations in K-ras gene was 1/8 (13%) in mucinous, 7/29 (24%) in serous, 1/3 (33%) in endometrioid and 2/8 (25%) in clear-cell adenocarcinomas and in H-ras gene 1/8 (13%) in mucinous and 2/29 (7%) in serous adenocarcinomas. Analysis of the results revealed no significant correlation between ras gene mutations and clinicopathological parameters or clinical outcome of this primary invasive ovarian carcinoma population. Our present data suggest that ras gene mutations in invasive ovarian carcinomas occur in 29% of Greek patients and are not associated with the differentiation of the epithelial cells or the response of patients to adjuvant platinum-based chemotherapy.
nm23 in the Primary and Metastatic Sites of Gastric Carcinoma
Authors: KumarDhar Dipok , Kubota Hirofumi , Tabara Hideki , Kotoh Tsukasa , Monden Naomi , Igarashi Masahiko , Kohno Hitoshi , Nagasue Naofumi
Published: April 2003

Tumor metastasis is the major cause of treatment failure and death in cancer patients. The present study was designed to extrapolate the association of nm23 expression with acquisition of metastatic potential of gastric carcinoma with special reference to the alpha-fetoprotein-producing gastric carcinoma (APGC). The primary tumor with surrounding normal mucosa and metastatic lymph nodes of 30 patients with APGC and 29 randomly selected matched controls of non-AFP gastric carcinoma (NAGC) were immunostained for nm23 and an image analyzer system was used for quantitative evaluation. Overexpression of nm23 was noted in 71% (42/59) of the primary tumors and 18% (10/55) of the metastatic tumors and there was no difference between the APGC and NAGC groups. The overexpression of nm23 in the primary tumors correlated with tumor invasion, metastasis and progression in all cases and similar results were obtained in the APGC and NAGC groups except for the tumor stage which was insignificant in the APGC group. The patient survival was adversely affected by the overexpression of nm23 in the primary sites and downregulation in the metastatic sites in all cases but lost their significance in the multivariate analysis. However, nm23 status did not affect patient survival in the APGC group.
A Comparative Study on Ferritin Concentration in Serum and Bilateral Bronchoalveolar Lavage Fluid of Patients with Peripheral Lung Cancer versus Control Subjects
Authors: Fracchia Antonio , Ubbiali Alessandro , ElBitar Omar , Pacetti Miriam , Sommariva Emanuela , Arreghini Marco , Longhini Erminio , Bonalumi GiovanniPaolo
Published: April 2003

Objectives: To assess the diagnostic value of bronchoalveolar lavage fluid (BALF) ferritin as a lung tumor marker by comparing serum and BALF ferritin concentrations in patients with peripheral lung cancer versus control subjects with benign lung disease, and to examine the theory of ferritin compartmentalization around the tumor area by comparing ferritin concentrations in serum and bilateral (affected and unaffected side) BALF in cancer patients. Methods: Four groups of patients were investigated: 10 control nonsmokers, 10 control smokers, 10 smokers with chronic obstructive pulmonary disease (COPD), and 22 patients with primary bronchogenic carcinoma. A bronchoalveolar lavage (BAL) was performed in all subjects (both sides in 13 oncological patients, one side in the others) and samples of BALF and blood were submitted to biochemical analysis. Results: As a lung tumor marker, BALF ferritin showed 54% sensitivity and 93% specificity and serum ferritin 22% sensitivity and 93% specificity. A significant difference was observed between the two sides in the cancer patients (p = 0.033), and between BALF ferritin from the affected side and COPD patients (p = 0.025). Greater differences were obtained when BALF ferritin in the affected side of cancer patients was compared with values in both control nonsmokers (p < 0.0001) and control smokers (p < 0.001). Conclusions: These findings seem to confirm the relative diagnostic value of BALF ferritin as a lung tumor marker and the theory of ferritin compartmentalization. However, further studies are required to clarify the relations between iron and ferritin on the one hand and inflammation, tumorigenesis and host response on the other.
Prognostic Classification of Malignant Melanomas by Combining Clinical, Histological, and Immunohistochemical Parameters
Authors: Otto Friedrich J. , Goldmann Torsten , Biess Brigitte , Lippold Andrea , Suter Ludwig , Westhoff Ulrike
Published: April 2003

In a retrospective study the prognostic relevance of clinical, histopathological, immunohistochemical, and flow-cytometric parameters in primary malignant melanomas was evaluated using both the receiver operating characteristic ROC procedure and the logistic regression model. The proteolytic enzymes collagenase IV, cathepsin B, and cathepsin D proved to be significant prognostic factors. Combining the results obtained with these enzymes with gender, anatomic site, tumour thickness, Clark’s level, ulceration, pattern of invasive growth, and presence of large round cells resulted in greatly improved discrimination between metastasized and non-metastasized cases. It is anticipated that this method could allow for precise individual prognostic characterization and in particular for identification of high-risk patients for adjuvant therapy.