Early Pseudomonas aeruginosa predicts poorer pulmonary function in preschool children with cystic fibrosis.

BACKGROUND: We previously reported relatively normal pulmonary function (2 years of age) and computed tomography (CT, 1 year of age) in cystic fibrosis (CF) newborn screened (NBS) infants. We now report follow up of these children to preschool age. METHODS: 67 NBS children with CF and 41 healthy controls underwent pulmonary function tests in infancy (∼3 months, 1 year and 2 years) and at preschool (3-6 years). Broncho-alveolar lavage (BAL) and CT were undertaken in those with CF at 1 year. Primary outcomes at preschool were lung clearance index (LCI) and forced expired volume (FEV0.75). Risk factors for lung function impairment were identified by regression modelling, emphasising factors that could be identified or measured in the first 2 years of life. RESULTS: At preschool age children with CF had poorer lung function than controls, mean(95% CI) difference in LCI z-score: 1.47(0.96;1.97) and FEV0.75 z-score -0.54(-0.98; -0.10). Isolation of Pseudomonas aeruginosa before 6 months was a highly significant predictor of raised (abnormal) preschool LCI, associated with a mean (95%CI) increase of 1.69(0.43, 2.95) z-scores, compared to those with no Pseudomonas aeruginosa during the first 2 years of life. Including 2 year LCI and 1 year CT data in the predictive model increased the r2 from 13% to 61%. CONCLUSIONS: Lung function deteriorates after 2 years in NBS children with CF. Isolation of Pseudomonas aeruginosa before 6 months and minor abnormalities of infant lung function tests and CT in infancy are associated with higher preschool LCI.

Paranasal sinus pathogens in children with cystic fibrosis: do they relate to lower respiratory tract pathogens and is eradication successful?

BACKGROUND: The study aims were to assess the association of microflora between the paranasal sinus and the lower airways of children attending a regional paediatric cystic fibrosis centre and to determine the performance of an eradication treatment protocol for positive paranasal sinus samples. METHOD: Paired nasal lavage and lower airway samples (cough swabs or sputum) were taken from 54 children with cystic fibrosis (median age 11 years). Positive paranasal sinus samples received eradication treatment, using oral and sinonasal nebulised antibiotics. RESULTS: A correlation between paranasal sinus and lower airways was detected in 33/54 paired timed samples (p<0.02). Of 4/54 children who reported sinus symptoms, only 2 had paranasal sinus positive samples. 28 positive nasal lavage samples cultured 8 Pseudomonas aeruginosa (PA), 8 Staphylococcus aureus (SA) and 12 other bacterial pathogens. Eradication using sinonasal nebulised antibiotics and oral antibiotics showed a success of 14/21 (67%) treated paranasal sinus positive samples at 1 month & 3 months after treatment. Success rate was 75% in the PA group and 71% in the SA group. Ongoing monitoring with nasal lavage will continue. CONCLUSION: There was agreement between pathogens or lack of them found in the paranasal sinus and lower airways. Paranasal infection is often asymptomatic in children with cystic fibrosis. The eradication protocol for paranasal sinus pathogens had a good success rate.

Loop conization for the treatment of microinvasive carcinoma of the cervix.

The purpose of the study was to evaluate the specimen adequacy and diagnostic accuracy of loop conization in microinvasive carcinoma of the cervix. A retrospective study was conducted from 1997 to 2003 at the Colposcopic Clinic, Department of Gynecology and Obstetrics, Chang Gung Memorial Hospital, Taipei, Taiwan. Sixty-three consecutive patients with microinvasive carcinoma of the cervix receiving cold-knife conization (35 patients) or loop conization (28 patients) were included in the study. All patients underwent definitive hysterectomy. We reviewed the conization specimen together with the hysterectomied uterus to compare the two conization techniques with respect to the histopathologic interpretation and diagnostic accuracy. The mean depth of cone specimens was significantly less in the loop conization compared with cold-knife conization (1.65 versus 2.35 cm, P = 0.035). Regarding the application of conization, the loop conization was completed in a single slice in 27 patients (77.1%) and in multiple slices in 8 patients (22.9 %), in spite of encouragement to perform conization in a one-pass application when possible. However, the cold-knife specimens were invariably a single cone-shaped piece. As reviewed by microscopic examination, the rate of tissue transection was significantly higher in the loop group than in the cold-knife group (14.3% versus 0%, P = 0.04). Because of tissue transection and disorientation, pathologic evaluation of stromal status was inadequate in 11.4% (4/35) of the loop cones as opposed to none of the 28 cold-knife cones. After assessing the hysterectomy specimens, the clinical diagnoses in the loop group were downgraded in three patients compared with only one in the cold-knife group. Data from this investigation suggest that cervical cold-knife conization is superior to loop conization as a method to assess microinvasive cervical cancer.

Enhancing cell viability with pulsating flow in a hollow fiber bioartificial liver.

A pulsating flow of medium was used to alleviate diffusion and transport limitations in a hollow fiber bioreactor containing a human hepatoblastoma cell line. The strategy is easy to implement but effective. The pulsating flow is introduced by a solenoid pinch valve at the outlet of the bioreactor and regulated by a timing circuit. In a permeability test, the system with pulsating flow had much less membrane fouling as compared to the control, a conventional hollow fiber unit. In hepatocyte culture test runs, the pulsating-flow bioreactor demonstrated the ability to maintain a higher cell viability. Histological sections indicated significantly smaller necrotic regions in the pulsating-flow bioreactor as compared to the conventional unit.

Simultaneous detection of double-stranded RNA-induced protein kinase and its specific mRNA by single cell analysis.

Fluorescent in situ hybridization was combined with flow cytometry to detect the expression of the double-stranded-RNA-induced protein kinase (PKR) in single cells. Labeled anti-sense oligonucleotide was used to target the specific mRNA while the protein was targeted with an antibody. It was demonstrated that the PKR-mRNA signal could be protected through a lengthy immunostaining procedure. The expression pattern of the PKR-mRNA with respect to DNA content was shown to be comparable to that of 18S ribosomal RNA.

Negative predictive value of human papillomavirus test following conization of the cervix uteri.

OBJECTIVE: The goal of this study was to determine/evaluate the negative predictive value of human papillomavirus (HPV) testing following conization of cervix uteri. METHODS: A prospective analysis was undertaken on 79 cone biopsies of women with high-grade lesions (cervical intraepithelial neoplasia (CIN) III). HPV testing was performed on cervical smears before and after conization. We correlated the margin status (defined as positive cone margin or endocervical curettage status) and positive conization HPV status with the residual disease in a hysterectomy specimen. A Digene II kit was used to perform HPV testing. HPV detection was done by Hybrid Capture assay. RESULTS: Of the 79 patients, 47(59.5%) had positive margins after conization. HPV testing was positive in 37 cases (78.7%) and negative in 10 cases (21.3%). Residual disease was found in 31 of 47 (66%) postconization hysterectomy specimens. No residual lesions were found in HPV-negative cases. Of the 32 cases with negative margins following conization, HPV testing was negative in 25 cases (78%) and was positive in 7 cases (22%). Among these 25 cases with negative HPV tests, no residual lesion was detected, and in 7 HPV-positive cases, only one residual lesion was found. CONCLUSION: HPV testing is potentially an effective tool in predicting residual dysplasia after conization and could potentially assist in the decision between hysterectomy and conservative follow-up in women with CIN III.

Applications of the telomerase assay in peritoneal washing fluids.

OBJECTIVE: The aim of this study was to detect telomerase activity in peritoneal ascites and to assess whether it can be used as an assistant tool for the early detection of ovarian cancer. METHODS: Telomerase activity was measured by TRAP assay in 47 patients with ovarian malignancies and 50 patients with benign uterine leiomyomas (control group). RESULTS: All 26 peritoneal washing cytology positive cases were telomerase positive. Of the 21 peritoneal washing cytology negative cases, 3 were telomerase positive. When these 3 were reevaluated for peritoneal cytology, malignant ascitis was identified in 1. All telomerase negative cases were negative for peritoneal washing cytology. The sensitivity and specificity of peritoneal cytology and telomerase testing in correlation with true malignant cells were 96 (26/27) and 100% (20/20) versus 100 (27/27) and 90% (18/20), respectively. The false negative rate of peritoneal cytology was 4.7% (1/21). The false positive rate of the telomerase test in relation to malignant ascites was 6.9% (2/29). CONCLUSION: Our preliminary results reveal a high sensitivity and specificity of both telomerase testing and conventional cytology in peritoneal fluids. Our data suggest that the telomerase test in peritoneal fluids can be used as an adjuvant to cytopathological methods in the diagnosis of malignant peritoneal ascites, particularly in cases of negative cytology. In these cases, a review of peritoneal histocytology is advised.

Detection of human papillomavirus types 16 and 18 mRNA in peripheral blood of advanced cervical cancer patients and its association with prognosis.

PURPOSE: To evaluate the feasibility of detecting human papillomavirus E6 (HPVE6) gene mRNA in the peripheral blood of patients with locally advanced cervical cancer, and the relationship of the circulating HPV viral-specific mRNA with clinicopathologic factors and prognosis of locally advanced cervical cancer. PATIENTS AND METHODS: The presence of types 16 and 18 HPVE6 gene mRNA was determined by reverse transcription followed by nested polymerase chain reaction. Thirty-five patients with locally advanced cervical cancer who were positive for HPV type 16 or 18 DNA were included in the study. All patients received external-beam radiation therapy followed by intracavitary brachytherapy. RESULTS: Eighteen (51.4%) of 35 HPV DNA-positive cervical cancer patients had HPV-specific mRNA in their peripheral blood cells, compared with none of 17 HPV DNA-negative cervical cancer patients and none of 12 control volunteers. The presence of HPVE6 gene mRNA in peripheral blood was associated with bulky tumor volume (> 4 cm) and pelvic lymph node metastasis (tumor volume, P = .03; lymph node status, P = .03). After a median follow-up of 22 months, patients who were positive for peripheral-blood HPVE6 gene mRNA had a significantly higher risk of recurrence than those who were negative (10 of 18 v three of 17, P = .02; mean recurrent time, 20.7 months v 12.6 months, P = .02). There was also a statistically significant association of peripheral-blood HPVE6 gene mRNA positivity with distant metastasis (eight of 18 vone of 17; P = .01). CONCLUSION: Results of this study seem to suggest that the presence of HPVE6 gene mRNA in peripheral blood may provide an early marker that identifies patients who are at risk for metastasis.

Evidence of Epstein-Barr virus in lymphoepithelioma-like carcinoma of the uterine cervix: a case report.

Lymphoepithelioma-like carcinoma of the uterine cervix is very rare. A 71-year-old woman, who had cervical cancer stage IB, presented lymphoepithelioma-like carcinoma pathologically. The neoplasm revealed an undifferentiated, nonkeratinizing carcinoma, which contained prominent vesicular nucleoli histologically. Epstein-Barr virus (EBV) DNA and HPV-16 DNA were demonstrated in cancer cells when using polymerase chain reaction. The patient underwent a radical hysterectomy with bilateral pelvic lymph node dissection and bilateral salpingooophorectomy. Her postoperative course was uneventful. The literature and pathologic findings are reviewed and discussed.

Regulation of murine fetal-placental calcium metabolism by the calcium-sensing receptor.

The calcium-sensing receptor (CaSR) regulates PTH secretion to control the extracellular calcium concentration in adults, but its role in fetal life is unknown. We used CaSR gene knockout mice to investigate the role of the CaSR in regulating fetal calcium metabolism. The normal calcium concentration in fetal blood is raised above the maternal level, an increase that depends upon PTH-related peptide (PTHrP). Heterozygous (+/-) and homozygous (-/-) disruption of the CaSR caused a further increase in the fetal calcium level. This increase was modestly blunted by concomitant disruption of the PTHrP gene and completely reversed by disruption of the PTH/ PTHrP receptor gene. Serum levels of PTH and 1, 25-dihydroxyvitamin D were substantially increased above the normal low fetal levels by disruption of the CaSR. The free deoxypyridinoline level was increased in the amniotic fluid (urine) of CaSR-/- fetuses; this result suggests that fetal bone resorption is increased. Placental calcium transfer was reduced, and renal calcium excretion was increased, by disruption of the CaSR. These studies indicate that the CaSR normally suppresses PTH secretion in the presence of the normal raised (and PTHrP-dependent) fetal calcium level. Disruption of the CaSR causes fetal hyperparathyroidism and hypercalcemia, with additional effects on placental calcium transfer.

Differential expression of interleukin-1 beta and interleukin-6 in human fetal serum and meconium-stained amniotic fluid.

The study was designed to investigate the expression of the inflammatory cytokines interleukin-1 beta and interleukin-6 in meconium-stained amniotic fluid and in fetal cord serum. Amniotic fluid and fetal cord serum specimens were collected from 10 and 9 women with meconium-stained and clear amniotic fluid, respectively, during Caesarean operation at labor The mean concentrations of interleukin-1 beta found in clear and meconium-stained amniotic fluid were 10.0 and 54.5 pg/ml, respectively, and the difference was not statistically significant. On the other hand, the concentrations of interleukin-6 in meconium-stained amniotic fluid (774 pg/ml) was significantly higher than that found in clear amniotic fluid (149 pg/ml) (P = 0.0036). The differences of levels of both interleukin-1 beta and interleukin-6 in fetal cord serum specimens were not significant between neonates born to mothers with either clear or meconium-stained amniotic fluid (P = 0.8702 and 0.2987, respectively). The results of this study suggest that the production of at least one of the inflammatory cytokines, interleukin-6, is associated with the meconium found in amniotic fluid.

Perinatal transmission of human papillomavirus in infants: relationship between infection rate and mode of delivery.

OBJECTIVE: To determine the transmission rate of human papillomavirus (HPV) in newborn infants of HPV-positive women and to assess the relationship between perinatal HPV transmission and mode of delivery. METHODS: Three hundred one pregnant women were selected: vaginal delivery (n = 160) or cesarean delivery (n = 141). We assessed the presence of the HPV types 16 and 18 DNA sequences in buccal and genital swabs of neonates born to HPV-positive mothers, using the polymerase chain reaction. RESULTS: The overall frequency of HPV 16/18 infection among the pregnant women was 22.6% (68/301). At birth, the overall frequency of HPV transmission from HPV 16/18-positive mothers to newborns was 39.7% (27/68). A significantly higher rate of HPV 16/18 infection was found at birth when infants were delivered vaginally than when infants were delivered by cesarean (18/35 or 51.4% versus 9/33 or 27.3%, P = .042). However, there was no significant difference in the incidence of perinatal HPV infection between the HPV types 16 and 18 in either vaginal delivery group or in the cesarean delivery group (all P > .100). No significant difference was found between the buccal and genital sites (27/68 versus 21/68, P = .234) or between male and female infants overall (12/36 versus 15/32, P = .255). CONCLUSION: The findings suggest that neonates are at higher risk for exposure to HPV after vaginal delivery than after cesarean delivery.

Lymphoepithelioma-like carcinoma of the uterine cervix: association with Epstein-Barr virus and human papillomavirus.

BACKGROUND: The presence of Epstein-Barr virus (EBV) has not been documented in previous reports of lymphoepithelioma-like carcinoma (LELC) of the uterine cervix by either polymerase chain reaction or in situ hybridization, and the histogenesis of the tumor remains unknown. Additionally, a relationship between human papillomavirus (HPV) and cervical LELC also has not been reported. METHODS: In this article, the authors describe the clinical and histopathologic findings for 15 patients with cervical carcinoma that had a histologic pattern of LELC. The polymerase chain reaction detected the presence of EBV and HPV DNA sequences in cervical LELC. RESULTS: All 15 tumors showed a typical syncytial growth pattern of undifferentiated cells with prominent lymphocytic infiltration. The detection rate of the EBV gene sequence in tissue samples from patients with LELC was more frequent than that in control patients with squamous cell carcinoma of the cervix (11 of 15 patients, 73.3%, vs. 4 of 15 patients, 26.7%; P = 0.01). However, the detection rate of HPV-16 and HPV-18 DNA was significantly lower in patients with LELC tumors than in patients with cervical squamous cell carcinoma (3 of 15 patients, 20.0%, vs. 12 of 15 patients, 80.0%; P = 0.001). After a median follow-up of 3.9 years (range, 1.8-5.3 years), the 15 patients showed no evidence of disease or metastasis after radical hysterectomy or radiotherapy. CONCLUSIONS: The finding of EBV associations in cervical LELC supports the hypothesis that EBV may be involved in the pathogenesis of tumors that arise in the cervix. It is possible that cervical LELC may follow a different pathway in the pathogenesis of LELC in Asian women as compared with the more common forms of squamous cell carcinoma.

The effect of human papillomavirus infection on sperm cell motility.

OBJECTIVE: To investigate the presence of human papillomavirus (HPV) in human sperm cells and to evaluate potential effects of HPV on the sperm functions. DESIGN: A descriptive clinical study. PATIENT(S): Specimens of semen were collected from 24 randomly selected patients who attended the fertility clinics at Chang Gung Memorial Hospital. MAIN OUTCOME MEASURE(S): The presence of HPV DNA and RNA were examined by polymerase chain reaction. Semen quality and sperm cell function were analyzed by computer-aided autoanalyzer. RESULT(S): Human papillomavirus type 16 DNA and RNA were found in 6 (25%) and 2 (8%) of the sperm cells specimens, respectively. Human papillomavirus type 18 DNA and RNA were present in 11 (46%) and 5 (21%) of the same sperm cells specimens, respectively. Incidence of asthenozoospermia among patients infected with either HPV was significantly higher than in those without HPV in their sperm cells (75% versus 8%). Although performance of curvilinear velocity, straight-line velocity, and mean amplitude of lateral head displacement was significantly lower in HPV-infected specimens, the differences of linearity, beat cross frequency, and straightness were not statistically significant. CONCLUSION(S): These results suggest that human papillomavirus can be found in human sperm cells and that certain HPV-specific genes are actively transcribed. Sperm motility parameters seem to be affected by the presence of HPV in the sperm cells, and also the incidence of asthenozoospermia may be associated with HPV infection.

Differential expression of telomerase activity in human cervical cancer and cervical intraepithelial neoplasia lesions.

PURPOSE: Telomeres are tandem arrays of repeated DNA sequences located at the ends of eukaryotic chromosomes, and are synthesized by the enzyme telomerase. Loss of telomeric DNA may play an important role in the development of human cancers. However, very little is known about the status of telomerase during human cervical cancer development. PATIENTS AND METHODS: Telomerase activity was measured by telomere repeat amplification protocol (TRAP) assay in 24 cervical cancers, one carcinoma in situ (CIS), and 20 cervical intraepithelial neoplasia (CIN) lesions. Adjacent nontumor cervical tissue from the same 24 cervical cancer patients and normal cervical tissues from 11 control individuals also were examined for the presence of telomerase activity. RESULTS: Twenty two of the 24 (91.7%) cervical cancer specimens and the single CIS tissue were strongly positive for telomerase activity. Relatively weak but distinctive telomerase activity also was detectable in one of four CIN-I (25%), two of eight CIN-II (25%), and two of eight CIN-III (25%), respectively. However, telomerase activity was not found in the 24 corresponding nontumor cervical tissues from the same cervical cancer patients and the 11 normal cervical tissues from control individuals. CONCLUSION: The majority of cervical cancers contain strong telomerase activity. Significant proportions of noncancerous CIN tissues also contain telomerase activity, although weaker than that in cervical cancer. It seems that there is a progressive increase of telomerase activity in association with an increased degree of cervical malignancy. These results seem to suggest that the expression of telomerase may play a crucial role in cervical cancer carcinogenesis.

Identification of human papillomavirus types 16 and 18 deoxyribonucleic acid sequences in bulky cervical cancer after chemotherapy.

OBJECTIVE: The objectives of this study were to evaluate the effect of chemotherapy on the continual presence of human papillomavirus deoxyribonucleic acid sequences in bulky cervical cancer tissues and the relationship between the presence of human papillomavirus and the response of these patients to chemotherapy. STUDY DESIGN: Multiple tissue sections obtained from 33 patients with bulky cervical cancer both before and after chemotherapy were analyzed for the presence of human papillomavirus types 16 and 18 by deoxyribonucleic acid amplification. RESULTS: The cytotoxic effects of chemotherapy did not significantly alter the continual presence of human papillomavirus deoxyribonucleic acid sequences in these tissues (p = 0.8048). The presence of human papillomavirus type 16 deoxyribonucleic acid in tumors treated with neoadjuvant chemotherapy was significantly associated with favorable tumor response compared with type 18-positive patients and type 16/18-negative patients (94.7% vs 42.9%, p = 0.0059 and 94.7% vs 44.4%, p = 0.0004, respectively). Additionally, patients with type 18 deoxyribonucleic acid had a significantly higher risk of recurrence than did type 16-positive patients (p = 0.0123). CONCLUSIONS: These results seem to suggest that the presence of human papillomavirus deoxyribonucleic acid sequences may serve as a marker to predict the response of bulky cervical cancer to chemotherapy and may be useful in reassessing neoadjuvant treatment for those patients who are free of human papillomavirus or those with type 18 deoxyribonucleic acid.

Detection of human papillomavirus mRNA and cervical cancer cells in peripheral blood of cervical cancer patients with metastasis.

PURPOSE: To determine the presence of cervical cancer cells in circulating peripheral blood of stage IVb cervical cancer patients with metastasis to distant organs. PATIENTS AND METHODS: Cervical cancer tissue from 15 stage IVb cervical cancer patients with metastasis were analyzed for the presence of human papillomavirus (HPV) type 16 DNA by nested polymerase chain reaction (PCR). The presence of transcriptional products of the HPV type 16 E6-transforming gene in the peripheral blood of the same 15 cancer patients was analyzed by reverse transcription and PCR. Cervical tissues and peripheral-blood specimens from 12 normal healthy individuals served as controls. RESULTS: Thirteen of 15 (86.7%) cervical cancer tissues from same number of patients were found to contain HPV type 16 DNA. Peripheral-blood specimens from 12 of 13 (92.3%) cervical HPV DNA-positive patients were found to contain HPV-specific mRNA detectable by reverse transcription (RT) and PCR. Cervical tissues from all 12 normal controls were HPV-free. None of the peripheral-blood specimens from two cervical HPV-negative cancer patients and 12 normal controls contained detectable amounts of mRNA of HPV type 16 E6-transforming gene. CONCLUSION: The most likely source of the HPV-specific mRNA detected in the peripheral blood of cervical cancer patients with metastasis is the cervical cancer cells derived from or shed from the cervix. The presence of HPV E6 mRNAs in peripheral blood may be a sensitive indicator of circulating cervical cancer cells. If PCR positivity is proven to be able to predict disease progression reliably, these findings may have clinical applications in the treatment of cervical and many other cancers.

Characterization of colorectal-cancer-related cDNA clones obtained by subtractive hybridization screening.

In an attempt to seek out new factors that are related to colorectal carcinogenesis at the molecular level, subtractive hybridization between cDNA of normal mucosal tissues and mRNA of colorectal carcinoma tissues was performed. Subsequent screenings of the cDNA libraries, constructed from normal mucosal tissues, using the "subtractive probes" generated a total of 46 clones that were expressed in normal mucosa but were either expressed at a significantly reduced level or not expressed at all in cancer tissues. Partial nucleotide sequences of all of these cDNA clones were determined, and sequence homology analyses were performed with the Genbank database. Of the 46 cDNA samples, 44 contained substantial sequence homologies with 32 immunoglobulin gene fragments, a helix-loop-helix basic phosphoprotein gene, an acidic ribosomal phosphoprotein P2 gene, a BLR1 gene for Burkitt's lymphoma receptor 1 gene, D5S419 DNA segment containing (C-A) repeats, a glucokinase (GCK) gene, a Na+, K+-ATPase alpha-subunit gene, a histocompatibility system HLA-DR heavy-chain gene, a dystrophic gene, a mucin (MUC2) gene, a mu-glutathione S-transferase gene, a Menkes disease protein gene, and a 40-kDa keratin intermediate filament precursor gene. The remaining two cDNA clones (now registered under GenBank accession numbers U17714 and U20428) showed few (less than 60%) sequence homologies with any known sequences in the GenBank database and, therefore, may represent novel genes whose expression was down-regulated in human colorectal carcinomas. The possible clinical significance of these findings and the involvement of these two genes in the carcinogenesis of colorectal as well as other cancers are being investigated.

Squamous cell carcinoma arising in mature cystic teratoma of the ovary.

Treatment results of 26 patients with squamous cell carcinoma (SCC) arising in mature cystic teratoma of the ovary were analyzed. Four nulliparous patients with stage Ia tumors underwent conservative salpingo-oophorectomy. Following surgery, 2 patients had successful pregnancies. The remaining 7 patients with stage Ia tumors were observed after hysterectomy and bilateral salpingo-oophorectomy. Fifteen patients with stage Ic-IV tumors underwent cytoreductive surgery followed by cis-platinum-based chemotherapy with or without sequential radiotherapy. The mean survival was 63.9 months. The overall actuarial disease-free survival at 2 years was 69%, and by stage was as follows: stage I, 100% (13/13); stage II, 100% (2/2); stage III, 30% (3/10); and stage IV, 0% (0/1). A significant difference in disease-free survival was noted in stage (P = 0.0001). Optimal versus suboptimal operation was associated with a median Kaplan-Meier survival of 65 months versus 34.8 months, with actuarial disease-free survival at 2 years of 60 and 0%, respectively (P = 0.0210). Our study shows that 67% (16/24) of the patients had SCC antigen levels exceeding 2 ng/ml, which by stage was as follows: stage I, 5/11 (45%); stage II, 1/2 (50%); stage III, 9/10 (90%); and stage IV, 1/1(100%). After completion of treatment, all 8 patients with recurrent lesions had reelevated SCC antigen levels in series SCC antigen monitoring. In conclusion, positive prognostic factors of disease-free survival were optimal cytoreduction and lower FIGO stage. We suggest that multimodality therapy, including aggressive cytoreduction followed by cis-platinum-based chemotherapy with or without sequential radiotherapy, is recommended. In addition, we suggest that serum SCC antigen monitoring may be helpful in early detection of cancer recurrence.