Comparison of different approaches to quantitative adenovirus detection in stool specimens of hematopoietic stem cell transplant recipients.

BACKGROUND: Adenoviruses almost invariably proliferate in the gastrointestinal tract prior to dissemination, and critical threshold concentrations in stool correlate with the risk of viremia. Monitoring of adenovirus loads in stool may therefore be important for timely initiation of treatment in order to prevent invasive infection. OBJECTIVES: Comparison of a manual DNA extraction kit in combination with a validated in-house PCR assay with automated extraction on the NucliSENS-EasyMAG device coupled with the Adenovirus R-gene kit (bioMérieux) for quantitative adenovirus analysis in stool samples. STUDY DESIGN: Stool specimens spiked with adenovirus concentrations in a range from 10E2-10E11 copies/g and 32 adenovirus-positive clinical stool specimens from pediatric stem cell transplant recipients were tested along with appropriate negative controls. RESULTS: Quantitative analysis of viral load in adenovirus-positive stool specimens revealed a median difference of 0.5 logs (range 0.1-2.2) between the detection systems tested and a difference of 0.3 logs (range 0.0-1.7) when the comparison was restricted to the PCR assays only. Spiking experiments showed a detection limit of 102-103adenovirus copies/g stool revealing a somewhat higher sensitivity offered by the automated extraction. The dynamic range of accurate quantitative analysis by both systems investigated was between 103 and 108 virus copies/g. CONCLUSIONS: The differences in quantitative analysis of adenovirus copy numbers between the systems tested were primarily attributable to the DNA extraction method used, while the qPCR assays revealed a high level of concordance. Both systems showed adequate performance for detection and monitoring of adenoviral load in stool specimens.

Persistence and reactivation of human adenoviruses in the gastrointestinal tract.

Reactivation of persistent human adenoviruses (HAdVs) is associated with high morbidity and mortality in paediatric haematopoietic stem cell transplant (HSCT) recipients. Although invasive HAdV infections mainly arise from the gastrointestinal (GI) tract, the specific sites of HAdV persistence are not well characterised. We prospectively screened biopsies from 143 non-HSCT paediatric patients undergoing GI endoscopy and monitored serial stool specimens from 148 paediatric HSCT recipients for the presence of HAdV by real-time PCR. Persistence of HAdV in the GI tract was identified in 31% of children, with the highest prevalence in the terminal ileum. In situ hybridisation and immunohistochemistry identified HAdV persistence in lymphoid cells of the lamina propria, whereas biopsies from five transplant recipients revealed high numbers of replicating HAdV in intestinal epithelial cells. The prevalence of HAdV species, the frequencies of persistence in the GI tract and reactivations post transplant indicated a correlation of intestinal HAdV shedding pre-transplant with high risk of invasive infection. HAdV persistence in the GI tract is a likely origin of infectious complications in immunocompromised children. Intestinal lymphocytes represent a reservoir for HAdV persistence and reactivation, whereas the intestinal epithelium is the main site of viral proliferation preceding dissemination. The findings have important implications for assessing the risk of life-threatening invasive HAdV infections.

[Ernst Wertheim, or the significance of the EBM of the cervical cancer]. / Ernst Wertheim, oder zum Stellenwert der EBM beim Zervixkarzinom.

In the field of gynecologic oncology, the beginning of the 20(th) century was dominated by a dispute between Wertheim and Schauta over the best surgical approach for cervical cancer in general, and the role of lymphonodectomy in particular. Since that time, important progress has been made with respect to diagnosis and therapy. This refers a) to the inclusion of patients with malignant diseases into clinical studies with the subsequent design and development of evidence based therapy strategies and b) on the important role of endoscopic techniques in gynecologic oncology. Some of the controversies of the "Wertheim/Schauta" era such as the "lymph node problem" are not fully resolved to date. The future will be most likely not based on diagnosis and therapy of cervical cancer, but on primary prevention with the introduction of a potent vaccination against HPV, which will be commercially available soon.

Estrogen-metabolizing gene polymorphisms and age at natural menopause in Caucasian women.

BACKGROUND: Lifestyle parameters, personal history and genetic factors are thought to affect the timing of natural menopause in humans. Based on their biological function, estrogen-metabolizing gene polymorphisms have been regarded as candidate genes for early menopause. METHODS: In the present cross-sectional, multi-centre study, we analysed nine single nucleotide polymorphisms of six estrogen-metabolizing genes [three estrogen-synthesizing genes, i.e. 17-beta-hydroxysteroid dehydrogenase type 1 (17-beta HSD), cytochrome P-450 (CYP) 17 and CYP19; and three estrogen-inactivating genes, i.e. catechol-O-methyltransferase (COMT), CYP1A1 and CYP1B1] by sequencing-on-chip-technology in 1360 Caucasian women with natural menopause. Women's lifestyle parameters, reproductive and personal histories were ascertained. RESULTS: Carriage of at least one mutant allele of the CYP1B1-4 Asn453Ser A--> G polymorphism (P = 0.004) and the number of full-term pregnancies (P < 0.001) were found to be independently associated with age at natural menopause. Women with at least one polymorphic allele of CYP1B1-4 experienced natural menopause earlier than non-carriers of the polymorphism [mean (SD) 48.6 (5.0) versus 49.4 (4.3) years]. Women with no, one, two and three or more full-term pregnancies experienced natural menopause at 48.5 (5.0), 48.8 (4.8), 49.5 (4.2) and 49.6 (4.6) years, respectively. CONCLUSION: We present the most comprehensive data on estrogen-metabolizing gene polymorphisms and timing of natural menopause to date. The number of full-term pregnancies and the CYP1B1-4 polymorphism are significant predictors of timing of natural menopause in Caucasian women.

Expression of matrix metalloproteinases in patients with uterine smooth muscle tumors: an immunohistochemical analysis of MMP-1 and MMP-2 protein expression in leiomyoma, uterine smooth muscle tumor of uncertain malignant potential, and leiomyosarcoma.

OBJECTIVE: Matrix metalloproteinases (MMPs) have been suggested to play an important role in tumor invasion and metastasis. We compared the expression of MMP-1 and MMP-2 protein in patients with leiomyoma, uterine smooth muscle tumor of uncertain malignant potential (STUMP), and leiomyosarcoma (LMS). METHODS: MMP-1 and MMP-2 expression was investigated by immunohistochemistry from paraffin-embedded tissue in 26 patients with leiomyoma, in 24 patients with STUMP, and in 21 patients with LMS. RESULTS: MMP-1 was expressed in 92% of leiomyomas, in 83% of STUMP, and in 86% of LMS, whereas MMP-2 was expressed in 12% of leiomyomas, in 17% of STUMP, and in 48% of LMS. A statistically significant difference regarding the frequency of MMP-2 expression was observed between LMS and STUMP (P =.025) as well as between LMS and leiomyoma (P =.006), but not between STUMP and leiomyoma (P >.05). Likewise, the staining intensity did significantly differ between LMS and leiomyoma (P =.025), but no statistical significant difference was observed between LMS and STUMP (P >.05) and between STUMP and leiomyoma (P >.05). CONCLUSION: The stronger MMP-2 expression in patients with LMS compared with STUMP and leiomyoma indicates that this protein might be a marker for tumor invasion or metastasis in patients with uterine LMS. Furthermore, MMP-2 seems to be a useful immunohistochemical parameter to distinguish cases of smooth muscle tumors in which histologic features are ambiguous or borderline. Further studies including larger numbers of patients are necessary to establish MMP-2 as a routine marker for tumor invasion and progression.

MMP-1 and MMP-2 expression in uterine leiomyosarcoma and correlation with different clinicopathologic parameters.

OBJECTIVE: Matrix metalloproteinases (MMPs) have been suggested to play an important role in tumor invasion and metastasis because they degrade a wide range of components of the extracellular matrix. In the present study, we analyzed the expression of MMP-1 and MMP-2 proteins in patients with uterine leiomyosarcoma. METHODS: MMP-1 and MMP-2 expression was investigated by immunohistochemistry from paraffin-embedded tissue sections in 21 patients with uterine leiomyosarcoma (LMS). The immunohistochemical findings were correlated with different clinicopathologic characteristics of the patients. RESULTS: MMP-1 was expressed in 86% and MMP-2 was expressed in 48% of uterine LMS. There was a statistically significant positive correlation between vascular space involvement and MMP-2 expression (P =.05) and between age and MMP-2 expression, with patients over 50 years old having significantly more frequent MMP-2-positive tumors than patients younger than 50 years (P =.006). The relationship between MMP-2 expression and tumor stage and recurrence disease did not reach statistical significance. A trend towards prolonged disease-free survival was observed in women with MMP-2-negative LMS compared with patients with MMP-2-positive LMS (P =.09). Furthermore, a univariate analysis revealed that early tumor stage (P =.0001), age at diagnosis less than 50 years (P =.02), and the absence of vascular space involvement (P =.04) were associated with longer overall survival. CONCLUSION: The statistically significant positive correlation between MMP-2 expression and vascular space involvement as well as the prolonged disease-free survival rate in patients with MMP-2 negative uterine LMS suggest that MMP-2 plays an important role in tumor invasion and metastasis. Further clinical studies with larger numbers of cases need to be performed to verify these findings.

Immunohistochemical expression of laminin-5 in cervical intraepithelial neoplasia.

OBJECTIVES: Laminin-5 is an attachment protein for epithelial cells. Several studies of a variety of cancers have reported increased expression of laminin-5 in carcinoma in situ and invasive cancer. This study was designed to investigate the correlation between the grade of cervical intraepithelial neoplasia and the immunohistochemical expression of laminin-5 in the cytoplasm and in the basement membrane underlining dysplastic squamous cells. METHODS: We used immunohistochemical methods to stain paraffin-embedded sections of cervical cone biopsies with a monoclonal antibody specifically targeting the 2-chain of human laminin-5 protein. The study sample included 175 slides: 7 normal cervical epithelium, 36 lesions of mild dysplasia, 50 lesions of moderate dysplasia, 81 lesions of severe dysplasia, and 1 invasive squamous cell carcinoma. RESULTS: We found a statistically significant correlation between the grade of cervical intraepithelial neoplasia and laminin-5 immunoreactivity in the cytoplasm (P < 0.01) and in the basement membrane (P = 0.03) by use of the Wilcoxon rank-sum test. CONCLUSIONS: According to previously published reports we confirmed with a higher number of cases a correlation of laminin-5 expression in the cytoplasm and/or basement membrane and grade of dysplastic lesion in the cervical epithelium. This study warrants further investigations with special interest to follow-up to investigate whether laminin-5 is a marker to predict the risk of progression of cervical intraepithelial neoplasia lesions.

Is high-risk human papillomavirus infection associated with cervical intraepithelial neoplasia eliminated after conization by large-loop excision of the transformation zone?

OBJECTIVE: To investigate whether high-risk HPV infection associated with cervical intraepithelial neoplasia (CIN) was successfully eliminated after electrosurgical conization by large-loop excision of the transformation zone (LLETZ). STUDY DESIGN: 142 women, who were admitted for conization of CIN 1-3 were recruited into a prospective follow-up study of HPV infection, including cervical sampling for HPV DNA before, and then 3, 6 and 12 months after surgery. We examined whether there were any differences in the rate of HPV DNA positivity after LLETZ between specific risk groups, such as patients with primary (i.e. before surgical treatment) high-risk HPV infection, CIN of different grades, and positive margins. RESULTS: We did not detect statistically significant differences between specific risk groups. According to the assay used (hybrid capture II) at the last follow-up visit 94% of primarily infected patients were completely free from infection with high-risk HPV types, while 6% had persisting HPV infection. CONCLUSIONS: With a detection limit of 5000 genomes/ml HPV DNA the hybrid capture II results revealed, that after electrosurgical removal of CIN in 94% of patients testing positive for high-risk HPV DNA prior to surgery were negative 12 months post-surgery.

Prognostic parameters in carcinosarcomas of the uterus: a clinico-pathologic study.

BACKGROUND: Carcinosarcomas of the uterus are highly aggressive malignant neoplasms with early lymphatic and hematogenous spread. The most important prognostic factor in carcinosarcoma is the extent of the tumor at the time of diagnosis. The prognostic impact of other factors such as myometrial invasion, menopausal age, age, parity and adjuvant therapy is still being discussed controversially. MATERIALS AND METHODS: Nineteen patients with histologically proven carcinosarcoma were included in the analysis. The patients were staged according to a modification of the International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer. For each patient, the histological material was reviewed by an experienced pathologist. Carcinosarcoma was defined histologically as any tumor of uterine origin composed of carcinomatous and sarcomatous components. RESULTS: The median follow-up time was 91 months (25% quartile, 47 months; 75% quartile, 145 months). The median overall survival of the 19 patients was 59 months, resulting in a 5-year overall survival rate of 43%. Three out of the nineteen (16%) patients demonstrated progressive disease while 6 out of 10 (32%) patients developed recurrent disease with a median disease free survival of 16 months (range 8-54). Eleven out of nineteen (58%) patients died of the disease. A univariate model revealed that early tumor stage (stage 1) (p<0.023), low myometrial invasion (p<0.017) and late onset of the menopause (p<0.050) were significantly associated with a lengthened overall survival in patients with carcinosarcoma. Age (p=0.34), parity (p=0.16) and adjuvant radiotherapy (p=0.45) did not influence overall survival of patients with carcinosarcoma. CONCLUSION: Early tumor stage, low myometrial invasion and late onset of the menopause are associated with a lengthened overall survival in patients with carcinosarcoma.

Perineal lacerations during spontaneous vaginal delivery.

BACKGROUND: The aim of the study was to assess the frequency of perineal lacerations during normal spontaneous vaginal delivery and to evaluate potential risk factors. METHODS: The study is based on an analysis of data from the obstetric database of the University Hospital of Vienna and the Semmelweis Women's Hospital Vienna, from February 1999 through to July 1999. Women with vaginal deliveries, uncomplicated pregnancies, uncomplicated first and second stage of labor, gestational age > 37 weeks and pregnancies with cephalic presentation were included. RESULTS: Of 1009 women, 36.2% had perineal lacerations (18.1% had first-degree, 15.2% second-degree, and 2.9% third-degree perineal tears). Univariate logistic regression models showed that only low parity (p = 0.004), the absence of episiotomy (p = 0.0001), and a large head diameter of the infant (p = 0.005) increased the risk for perineal laceration. After adjustment in multivariate analysis, low parity (p = 0.0001), the absence of episiotomy (p = 0.0001) and a large head diameter (p = 0.0004) remained independent risk factors for perineal laceration. Additionally, advanced age of the mother was associated with an increased risk of perineal laceration (p = 0.03). When analyzing the probability for third-degree perineal tears, a strong association with primiparity (p = 0.01), the use of episiotomy (p = 0.0001), a prolonged second stage of labor (p = 0.0001), a large head diameter of the infant (p = 0.01) and the use of oxytocin (p = 0.008) was found. CONCLUSIONS: Primiparous women who are being delivered of a large child are at a greater risk for severe perineal lacerations. In the study population episiotomy did not appear to protect against severe perineal lacerations.

Analysis of the human progesterone receptor gene polymorphism progins in Austrian ovarian carcinoma patients.

Ovarian carcinoma is the highest death cause in gynecologic malignancies. Although the molecular basis for familial breast and ovarian cancer is elucidated, few genetic markers have been associated with sporadic ovarian carcinoma. A polymorphism in intron G of the human progesterone receptor (PgR), caused by an Alu insertion, was described to be associated with ovarian carcinoma in a pooled German/Irish population. Later on, a G to T substitution in exon 4, causing a Valine to Leucine change in the hinge region of the receptor, and a synonymous C to T substitution in exon 5 were reported to be linked to the Alu insertion. This complex of the PgR gene polymorphism was designated PROGINS. In order to investigate if PROGINS is associated with risk for ovarian cancer in Austrian women, we analyzed DNA from 226 Austrian patients with sporadic ovarian carcinoma and a control group with 194 healthy volunteers for the PROGINS complex. The PROGINS status was studied in association with risk for ovarian carcinoma, the age of the ovarian patients, the protein level of PgR and estrogen receptor (ER) and histopathological parameters. The results indicate that the frequency of PROGINS carriers in Austrian women is similar to those in women in North America and England. There is no significant difference between the PROGINS allele distribution in ovarian carcinoma patients and healthy women. The PROGINS is not associated with increased risk for ovarian carcinomas. Additionally, the protein levels of ER and PgR were independent of the PROGINS status.

Novel MUC1 splice variants are expressed in cervical carcinoma.

OBJECTIVES: The MUC1 antigen can be used to identify epithelial cells from the background of hemopoietic cells. The present investigation describes patterns of overexpression of two novel MUC1 splice variants in human cervical carcinoma cell lines. METHODS: RT-PCR was carried out to determine MUC1 splice variants in the cervical cancer cell lines C-4 II, C-33A, DoTc 2 4510, C-4 I, SiHa, HT3, Hs 636 T (C4-I), and HeLa. RESULTS: The novel MUC1 splice variant D was expressed in all cell lines and the novel MUC1 splice variant C was expressed in all cell lines but C-33A. Variants A and B were expressed in all (variant A) and all but one (variant B) cell line. MUC1/REP was expressed in all cell lines and MUC1/SEC was positive in all but two cell lines (C-33 A, DoTc 2 4510). All but one cell line (C-33A) expressed MUC1/X and MUC1/Y, and two cell lines (C-33 A, DoTc 2 4510) did not express MUC1/Z, respectively. MUC1 variants A, D, and REP could be demonstrated consistently among all eight cervical carcinoma cell lines we have examined. CONCLUSIONS: The present study describes the feasibility of detecting a large number of MUC1 variants, including MUC1 variants C and D which are described for cervical carcinoma cells for the first time. Further studies will examine the presence of MUC1 splice variants' expression in human cervical carcinoma tissue.

Risk factors for third-degree perineal tears in vaginal delivery, with an analysis of episiotomy types.

OBJECTIVE: To determine the risk factors for third-degree perineal tears during vaginal delivery and to investigate the relation between different types of episiotomy and the occurrence of such tears. STUDY DESIGN: This retrospective multicenter study consisted of an analysis of data from the delivery databases of the University Hospital of Vienna and Semmelweis Frauenklinic Wien between February and July 1999. The study was restricted to a sample that included all women with uncomplicated pregnancy as well as uncomplicated first and second stages of labor, gestational age > 37 weeks and a pregnancy with cephalic presentation. Women with multiple gestations, noncephalic presentation, cesarean deliveries, shoulder dystocia and gestational age < or = 37 weeks were excluded from the study. RESULTS: Among the 1,118 births, 37 women (3.3%) experienced third-degree perineal tears. The use of episiotomy per se and the type of episiotomy (midline) as well as forceps delivery, primiparity, large infant head diameter, prolonged second stage of labor and use of oxytocin were identified as risk factors for third-degree perineal tears during vaginal delivery. When analyzing different types of episiotomy, there was approximately a sixfold-higher risk of third-degree perineal tears in women undergoing midline episiotomy as compared to mediolateral episiotomy. A stepwise logistic regression analysis revealed that episiotomy, prolonged second stage of labor and large infant head diameter remained independent risk factors for third-degree perineal tears. CONCLUSION: We found several risk factors for third-degree perineal tears. The use of midline episiotomy was associated especially with an increased risk of severe anal sphincter tears. To prevent women from long-term sequelae due to third-degree perineal tears, avoidable risk factors should be minimized whenever possible.

High frequency of allelic imbalance at regions of chromosome arm 8p in ovarian carcinoma.

Progressive genetic changes such as the inactivation of tumor suppressor genes (TSG) are thought to play an important role in the initiation and progression of ovarian cancer. Frequent nonrandom allelic imbalance (AI) at 8p11-p21 and 8p22-pter suggests the existence of TSGs that may be involved in the carcinogenesis of several human malignancies. We investigated 70 ovarian tumors with 11 highly polymorphic markers spanning 8p12-p21 and 8p22-pter to produce an AI map of 8p in epithelial ovarian cancer. Allelic imbalance was demonstrated in 54 tumors (77%), most frequently occurring at D8S136 (54%) and at D8S1992 (55%). Poorly differentiated and advanced stage cancers were more often affected by AI (G1+G2 vs. G3; 20% vs. 66%; stage I+II vs. III+IV, 36% vs. 54%, P<.001; Kruskal-Wallis test) than well differentiated and early stage tumors. There was no relationship between histological subtype and AI. Smallest regions of overlap (SRO) were delineated by analyzing 38 tumors with partial AI. This study provides compelling evidence for the involvement of TSGs on the short arm of chromosome 8, at 8p12-p21 and at 8p23 in the development and progression of epithelial ovarian cancer.

Three-dimensional ultrasound of the female urethra: comparing transvaginal and transrectal scanning.

OBJECTIVES: To compare transvaginal and transrectal three-dimensional ultrasound in determining the morphology and measurements of the female urethra. DESIGN: Sixty-five women who had not had surgery for incontinence or pelvic floor descent had transvaginal and transrectal sonography using a 7.5-MHz mechanical sector endoprobe with three-dimensional facilities. The multiplanar display of the scanned volumes allowed detailed morphologic assessment of the urethra and the measurement of distances and volumes. Statistical endpoints were: sagittal urethral diameter, maximum rhabdosphincter length and thickness, maximum thickness of the smooth muscle complex, and the volumes of the rhabdosphincter and the smooth muscle complex. Values were compared between the two approaches using Student's t-test and Bland-Altman analysis. RESULTS: Both vaginal and rectal scans were feasible. However, significant differences between the two approaches were found for the sagittal diameter of the urethra (8.4 +/- 1.9 mm on vaginal vs. 11.5 +/- 2.2 mm on rectal scans, P < 0.01) and the transverse diameter of the urethra's smooth muscle complex (11.2 +/- 0.3 mm on vaginal vs. 8.6 +/- 0.2 mm on rectal scans, P < 0.001). No other variables showed significant differences. Compression of the urethra and displacement under the symphysis pubis were observed when the ultrasound probe was applied vaginally. Bland-Altman analysis showed acceptable variability for differences of distances but considerable variability for the differences of volumes. CONCLUSION: The female urethra can be examined both vaginally and rectally by three-dimensional ultrasound. A transvaginally applied probe seems to have a compression effect on the urethra.

Prognostic parameters in endometrial stromal sarcoma: a clinicopathologic study in 31 patients.

OBJECTIVE: The aim of this study was to evaluate the behavior of endometrial stromal sarcomas (ESS) in relation to their clinical and pathologic features and to identify possible prognostic factors. METHODS: Thirty-one patients with histologically proven ESS were included in the analysis. Endometrial stromal sarcoma is characterized by proliferations composed of cells with endometrial stromal cell differentiation. A breakpoint of 10 mitoses per 10 high-power fields was used in the statistical analysis to distinguish between low-grade and high-grade endometrial stromal sarcoma and to evaluate the prognostic value of mitotic count in patients with ESS. RESULTS: The median follow-up time was 72 months (range 34-110). The median overall survival of the 31 patients was 127 months, resulting in a 5-year overall survival rate of 62%. Adjuvant therapy was administered to 25 patients; among those, 20 patients received postoperative radiotherapy and 5 patients received chemotherapy. Ten of the irradiated patients and 3 patients undergoing chemotherapy developed disease recurrence. Concerning the response rate to adjuvant chemotherapy, 1 patient showed a complete response, 1 patient a partial response, 1 patient stable disease, and 2 patients progressive disease. Altogether, 14 patients developed recurrent disease with a median disease-free survival of 11 months (range 5-60). Twelve patients died of the disease. A univariate model revealed that early tumor stage (P < 0.0007), low myometrial invasion (P < 0.008), and low mitotic count (P < 0.005) were associated with a lengthened overall survival in patients with endometrial stromal sarcoma. Age and adjuvant therapy did not influence overall survival of patients with ESS. CONCLUSION: Early tumor stage, low myometrial invasion, and low mitotic count are associated with a lengthened overall survival in patients with ESS.

Paclitaxel-carboplatin chemotherapy does not cause encephalopathy in patients with ovarian cancer: a prospective EEG mapping study in 28 patients.

BACKGROUND: The objective of this study was to evaluate possible effects of a paclitaxel containing chemotherapy, on the central nervous system (CNS) in women with ovarian cancer. MATERIALS AND METHODS: Twenty-eight women with histologically documented epithelial ovarian carcinoma and treated with a combination chemotherapy consisting of paclitaxel and carboplatin entered the study. Patients were tested with resting EEG (R-EEG) before and after chemotherapy. RESULTS: Twenty of the 28 patients responded to the chemotherapy (71%). Eleven patients (39%) developed peripheral neurotoxicity. A decrease of beta power and an increase of delta and theta power as well as a deceleration of the total centroid frequency clearly demonstrated a reduced vigilance in patients with ovarian cancer compared to healthy controls. On the other hand, the observed increase of beta power, a decrease of delta and theta power, and an acceleration of the total centroid from pre- to post-treatment demonstrated an improvement of vigilance in patients with ovarian cancer after treatment with paclitaxel/carboplatin. CONCLUSIONS: The results of this study suggest that chemotherapy consisting of paclitaxel and carboplatin does not cause adverse effects on the central nervous system. Improved vigilance was measured in patients with ovarian cancer after chemotherapy.

Serum levels of angiogenin (ANG) in invasive cervical cancer and in cervical intraepithelial neoplasia (CIN).

BACKGROUND: The propensity of malignant tumors to increase in size, to invade locally and to metastasize is dependent on angiogenesis, which is induced by a variety of proteins including the family of fibroblast growth factors, vascular endothelial growth factor and angiogenin (ANG). The aim of the present study was to measure the serum levels of ANG in patients with CIN and invasive cervical cancer and to evaluate a possible correlation between ANG and various clinicopathologic parameters. MATERIALS AND METHODS: Blood was collected from 62 patients with invasive cervical cancer and 47 patients with CIN. Serum samples of 30 age-matched healthy women acting as a control group were obtained. Determination of serum levels of ANG was performed using a quantitative human ANG immunoassay. RESULTS: The overall median ANG serum level was 272.0 pg/ml (range 101.6-869.2). The median serum levels of ANG were 248.9 (range 101.6-307.2) for healthy female controls, 246.8 (range 169.7-468.1) for patients with CIN and 308.1 pg/ml (range 180.1-869.2) for patients with invasive cervical cancer. Serum levels of ANG were significantly elevated in patients with invasive cervical cancer compared with patients with CIN (p < 0.05) as well as healthy female controls (p < 0.05). No difference was found between ANG serum levels in women with CIN, and healthy controls (p < 0.05). No correlations were found between serum levels of ANG and clinico-pathologic parameters (p > 0.05). CONCLUSIONS: Our data indicate the important role of ANG in tumor angiogenesis in invasive cervical cancer as ANG serum levels were significantly elevated in these patients. However, elevated ANG serum levels seem to occur only after the transformation from pre-invasive to invasive lesions.

Interleukin-8 serum level shift in patients with ovarian carcinoma undergoing paclitaxel-containing chemotherapy.

BACKGROUND: Paclitaxel has been described to induce interleukin-8 (IL-8) transcription and secretion in human ovarian carcinoma cells. The objective of this study was to investigate possible clinical implications of the effect of paclitaxel on IL-8 serum levels in patients suffering from ovarian carcinoma. METHODS: Thirty-one patients with ovarian carcinoma who were treated with combination chemotherapy consisting of paclitaxel and carboplatin entered the study. IL-8 serum levels and CA 125 serum levels were detected three times for each patient directly before chemotherapy, after three cycles of chemotherapy, and after six cycles of chemotherapy. In addition, serum samples from 59 healthy, age-matched women were obtained. A quantitative human IL-8 immunoassay was used to determine the IL-8 serum levels. RESULTS: Seventy-eight percent of patients responded to chemotherapy, with 61% achieving a complete response and 16% achieving a partial response. The median IL-8 serum level before chemotherapy was 75 pg/mL (range, 2.7-903.3 pg/mL), the level during chemotherapy was 23.75 pg/mL (range, 0.5-248.2 pg/mL), and the level after chemotherapy was 17.65 pg/mL (range, 0.6-377.0 pg/mL). The median IL-8 serum level in controls was 15.6 pg/mL (range, 1.4-106.3 pg/mL). The authors found a statistically significant decrease in both IL-8 serum levels (P < 0.05 and P < 0.05) and CA 125 serum levels (P < 0.05 and P < 0.05) from the first to the second measurement and from the first to the third measurement, respectively. They found no correlation between the shifts of IL-8 serum levels and CA 125 serum levels during chemotherapy. CONCLUSIONS: The authors found a significant decrease in IL-8 serum levels in patients undergoing a paclitaxel-containing chemotherapy regimen, indicating that IL-8 possibly acts as a useful monitoring marker in patients with ovarian carcinoma.

Fibrosarcoma of the uterus: a case report.

BACKGROUND: This case report presents the management of a patient with fibrosarcoma of the uterus. Until recently, no cases of fibrosarcomas of the uterus have been reported in the literature. CASE REPORT: A 40-year-old woman presented with complaints of slight vaginal bleeding, watery, white discharge and abdominal pain of 3 weeks' duration. The patient underwent total abdominal hysterectomy. Intraoperative findings included an enlarged irregular-shaped uterus with lots of leiomyoma nodules. The largest leiomyoma nodule was about 8 cm in size and contained an area classified as a fibrosarcoma, presenting cellular immature-appearing fibroblasts growing in a fascicular arrangement. Because of the limited extension of the fibrosarcoma, no adjuvant therapy was performed. After surgical therapy the patient was followed without any evidence of disease for five years. CONCLUSION: Fibrosarcoma is a poorly-circumscribed infiltrative spindle soft tissue sarcoma, which is characterized by local growth and has a propensity for local recurrence. Metastases can occur, mostly to lung and bone. The treatment of choice is wide surgical excision usually followed by radiation therapy due to the high local recurrence rate.