Impact of hospital type and treatment on long-term survival among patients with FIGO Stage IIIC epithelial ovarian cancer: follow-up through two recurrences and three treatment lines in search for predictors for survival.

The purpose of this study was to investigate the impact of hospital type determined at primary treatment and find possible predictors of survival in a cohort of patients with advanced epithelial ovarian cancer (EOC) who recurred twice and received three lines of treatment during eight-year follow-up. Using the Norwegian Cancer Registry, the authors identified 174 women with FIGO Stage IIIC EOC diagnosed in 2002. First-line treatment consisted of up-front debulking surgery and chemotherapy, received in either a teaching hospital (TH, n = 84) or a non-teaching hospital (NTH, n = 90). After recurrence all patients in Norway are equally consulted at TH. Survival determined for three time intervals (TI): TI-1, from end date of first-line treatment to first recurrence or death, TI-2, from beginning of second-line treatment until second recurrence or death, and TI-3, from beginning of third-line treatment to death or end of follow-up. Extensive surgery carried out in TH followed by at least six cycles of platinol-taxan chemotherapy resulted in longer survival in the TH group during TI-1. Altogether, the majority of those who receive treatment for recurrences were primary better debulked with following platinol-taxane chemotherapy. Survival in TI-2 was influenced by platinol-sensitivity. During TI-3 the majority (96%) had good performance status and their mean age at primary diagnosis at either hospital type was 57 years. Extensive primary surgery at TH, platinol sensitivity, age, and performance status were predictors of survival in this cohort.

Fertility and gonadal function after adjuvant therapy in women diagnosed with a malignant ovarian germ cell tumor (MOGCT) during the "cisplatin era".

PURPOSE: By self-report and serum levels of anti-Mullerian hormone (AMH) this study aims to assess post-treatment fertility after modern treatment of women with malignant ovarian germ cell tumors (MOGCT). PATIENTS AND METHODS: In 2013 a questionnaire-based survey was performed in 61 MOGCT patients diagnosed at age <40years from 1980-2009. Forty-nine of them also attended the out-patient clinic. The event of first post-treatment pregnancy ("fertility") was documented as cumulative estimates for all 61 patients and within each of 4 treatment groups: Group 1: Surgery only (n=10); Group 2: ≤3cycles of cisplatin-based chemotherapy (CBCT) (n=20); Group 3: >3cycles of CBCT (n=15) and Group 4: other adjuvant treatment (n=16). AMH was determined in 22 women <40years at survey. Statistics were based on Kaplan Meier procedure, log-rank test and a significance level p<0.05. RESULTS: At least one post-treatment pregnancy was reported by 34 of 39 MOGCT survivors who attempted motherhood after treatment. The 15-year cumulative post-treatment fertility estimate was 28% (95% CI: 26-30) for all 61 survivors and was significantly higher in patients treated with 3 or fewer cycles of CBCT (53% [95% CI: 50-55]) than those treated with more than 3cycles (20% [95% CI: 17-22]) (P=0.03). Of 22 AMH levels, two were <3pmol/l, with one women being pregnant at survey. CONCLUSION: After fertility-sparing surgery and modern cisplatin-based chemotherapy, fertility is preserved in most MOGCT survivors though dependent on the number of cycles. AMH's role as a biomarker of gonadal function seems promising but requires further research.

Malignant ovarian germ cell tumors: presentation, survival and second cancer in a population based Norwegian cohort (1953-2009).

PURPOSE: To quantify and compare survival in women with malignant ovarian germ cell tumors (MOGCTs) in Norway before and after the introduction of cisplatin-based chemotherapy (around 1980), and to explore the association between different types of treatment and the development of a second cancer. PATIENTS AND METHODS: We identified 351 patients diagnosed with MOGCTs from 1953 to 2009 in the Cancer Registry of Norway. Ovarian cancer-specific survival was calculated separately for patients diagnosed before and after 1980. Patients were divided into subgroups by histological subtype (pure dysgerminoma, malignant teratoma, other MOGCTs) and extent of disease (localized and metastatic). We estimated the cumulative incidence of a second cancer in 10-year MOGCT survivors. Kaplan-Meier estimates were used, and p<0.05 was considered significant. RESULTS: 20-Year ovarian cancer-specific survival increased from 59% (95% CI 51% to 66%) before 1980 to 88% (95% CI 83%-93%) thereafter. Significant improvement was observed in all subgroups. No second cancer was diagnosed in any of 31 10-year MOGCT survivors treated with surgery only; second cancer was diagnosed in 23 of 139 patients who underwent cytotoxic treatment (98 radiotherapy ± chemotherapy, 41 chemotherapy only; p=0.08). Patients aged >50 years had a significantly poorer ovarian cancer-specific survival than younger patients (HR=5.98, 95% CI 3.39-10.57) after adjustment for histological subtype and stage at presentation. Our results favor the treatment of patients with metastatic MOGCTs at large cancer centers. CONCLUSION: Today women with MOGCTs have an excellent prognosis if treated according to modern therapeutic principles.

Final overall survival results of phase III GCIG CALYPSO trial of pegylated liposomal doxorubicin and carboplatin vs paclitaxel and carboplatin in platinum-sensitive ovarian cancer patients.

BACKGROUND: The CALYPSO phase III trial compared CD (carboplatin-pegylated liposomal doxorubicin (PLD)) with CP (carboplatin-paclitaxel) in patients with platinum-sensitive recurrent ovarian cancer (ROC). Overall survival (OS) data are now mature. METHODS: Women with ROC relapsing > 6 months after first- or second-line therapy were randomised to CD or CP for six cycles in this international, open-label, non-inferiority trial. The primary endpoint was progression-free survival. The OS analysis is presented here. RESULTS: A total of 976 patients were randomised (467 to CD and 509 to CP). With a median follow-up of 49 months, no statistically significant difference was observed between arms in OS (hazard ratio = 0.99 (95% confidence interval 0.85, 1.16); log-rank P = 0.94). Median survival times were 30.7 months (CD) and 33.0 months (CP). No statistically significant difference in OS was observed between arms in predetermined subgroups according to age, body mass index, treatment-free interval, measurable disease, number of lines of prior chemotherapy, or performance status. Post-study cross-over was imbalanced between arms, with a greater proportion of patients randomised to CP receiving post-study PLD (68%) than patients randomised to CD receiving post-study paclitaxel (43%; P < 0.001). CONCLUSION: Carboplatin-PLD led to delayed progression and similar OS compared with carboplatin-paclitaxel in platinum-sensitive ROC.

First-line treatment of advanced ovarian cancer with paclitaxel/carboplatin with or without epirubicin (TEC versus TC)--a gynecologic cancer intergroup study of the NSGO, EORTC GCG and NCIC CTG.

BACKGROUND: The addition of anthracyclines to platinum-based chemotherapy may provide benefit in survival in ovarian cancer patients. We evaluated the effect on survival of adding epirubicin to standard carboplatin and paclitaxel. PATIENTS AND METHODS: We carried out a prospectively randomized phase III study comparing carboplatin plus paclitaxel (TC; area under the curve 5 and 175 mg/m(2)) with the same combination and epirubicin (TEC; 75 mg/m(2) i.v.). Between March 1999 and August 2001, 887 patients with epithelial ovarian, tubal or peritoneal cancer International Federation of Gynecology and Obstetrics stages IIB-IV were randomized to receive either TC (442 patients) or TEC (445 patients). RESULTS: Median time to progression was 16.4 months in the TEC arm and 16.0 months in the TC arm (hazard ratio 0.99; 95% confidence interval [CI]: 0.9-1.2). Median overall survival time was 42.4 months for the TEC arm and 40.2 for the TC arm (hazard ratio 0.96; 95% CI: 0.8-1.1). Grade 3/4 hematologic toxic effects and most grade 3/4 non-hematologic toxic effects were more frequent in the TEC arm. Accordingly, a quality-of-life analysis showed inferiority of TEC versus TC. CONCLUSION: The addition of epirubicin to standard carboplatin and paclitaxel treatment did not improve survival in patients with advanced ovarian, tubal or peritoneal cancer.

Improved 5-year disease-free survival for FIGO stage I epithelial ovarian cancer patients without tumor rupture during surgery.

OBJECTIVE: To investigate the impact of perioperative capsule rupture on disease-free survival (DFS) and cancer-specific survival (CSS) in patients with FIGO stage I epithelial ovarian cancer (EOC I). METHODS: This prospective population-based study enrolled all 279 patients with EOC I diagnosed in Norway between 2002 and 2004. All patients underwent primary surgery. The data were collected from notification reports to the Norwegian Cancer Registry and included medical, surgical and histopathological records. Kaplan-Meier plots were used to show differences in DFS and CSS. Cox regression analyses were used to show the effect of prognostic factors on survival, expressed as hazard ratios (HRs). RESULTS: Significantly more patients in the capsule rupture group (Cr group) had clear cell tumors (28%) than in the FIGO stage IA and IB (AB group: 14%) groups, and the FIGO stage IC (C group: 17%; p<0.05) group. Despite adjuvant chemotherapy (AC), these patients had a poor 5-year DFS, 94% in the non-AC group and 81% in the AC group (p<0.01). After five years of follow-up, there was a lower DFS among patients in the Cr group (79%) and the C group (81%), compared with patients in the AB group (91%; p<0.05). Independent prognostic factors at the time of diagnosis were grade, histological type, ascites, adhesions, performance status, CA125 and DNA ploidy. After correcting for the four most important prognostic factors (grade, histological type, ascites, and DNA ploidy), the HR for recurrence was 4.0 (95% CI 1.3-12.7; p<0.05) for the Cr group and 1.8 (95% CI 0.5-6.1; p=0.3) for the C group, compared with the AB group. CONCLUSIONS: Improvement was observed in the 5-year DFS for EOC I patients without tumor rupture during surgery compared with those with tumor rupture. Since AC did not improve the long-term DFS and CSS rates, it is of utmost importance that surgeons avoid tumor rupture during surgery.

Diagnosis and treatment of borderline ovarian neoplasms "the state of the art".

The 5-year survival for women with Stage-I borderline tumours (BOT) is favourable, about 95-97%, but the 10-year survival is only between 70 and 95%, caused by late recurrence. The 5-year survival for Stage II-III patients is 65-87%. Standard primary surgery includes bilateral SOEB, omentectomy, peritoneal washing and multiple biopsies. Second cytoreductive surgery is recommended for patients with recurrent disease. Adjuvant postoperative therapy is not indicated in Stage-I diploid tumors. Occasional responses to chemotherapy have been reported in advanced BOTs but no study has shown improved survival. Recently a new theory has been developed describing a subset of S-ovarian cyst adenomas that evolve through S-BOT to low-grade carcinoma. A more correct staging procedure, classification of true serous implants and agreement on the contribution to stage of the presence of gelatinous ascites in mucinous tumours may in the future change the distribution of stage and survival data by stage for women with BOT. Independent prognostic factors in patients with epithelial ovarian BOT without residual tumour after primary surgery are DNA-ploidy, international FIGO-stage, histologic type and patient age. Studies on other molecular markers have not yet uncovered a reliable prediction of biologic behaviour, however, there is hope that future studies of genetics and molecular biology of these tumours will lead to useful laboratory tests. Future questions to be addressed in this review include the following: Have patients with borderline tumours in general been over-treated and how should these patients be treated? How to define the high-risk patients? In which group of patients is fertility-sparing surgery advisable and, do patients with borderline tumours benefit from adjuvant treatment?

Expression of matrix metalloproteinase-2 in serous borderline ovarian tumors is associated with noninvasive implant formation.

OBJECTIVE: To investigate matrix metalloproteinase (MMP) proteolytic and vascular endothelial growth factor (VEGF) and receptor (VEGFR-1, VEGFR-2) angiogenetic capacity in serous borderline ovarian tumors (S-BOTs) for women with and without noninvasive implants. METHODS: The population was made up of 99 patients with S-BOTs as the primary diagnosis between 1985 and 1995, 44 of whom had noninvasive implants and 55 without implants. MMP-2, MMP-14, the type-2 tissue inhibitor of MMPs (TIMP-2), and VEGF and receptors (VEGFR-1, VEGFR-2) were examined by immunhistochemistry. RESULTS: Strong positive (+++) MMP-2 staining was found more frequently in women with primary S-BOTs and noninvasive implants (76%) than in those without implants (53%; p < 0.05). In contrast, staining for MMP-14 and TIMP-2 was not significantly different in the two groups. Furthermore, expression of MMP-2, MMP-14, and TIMP-2 was similar in primary tumors and in their noninvasive implants. Most tumors in both groups had no VEGF expression (84% in the noninvasive implant group and 82% in the group without implants), while moderate (++) to strong (+++) expression of VEGFR-1 and VEGFR-2 was detected in 79% and 94% of the two tumor groups, with no significant difference between the groups. CONCLUSIONS: Enhanced MMP-2 was seen in primary S-BOT with noninvasive implants. The presence of noninvasive implants was prognostic for disease-free survival.

Primary surgery for ovarian cancer.

AIM: Review studies on survival outcomes for all survival treatment methods of primary ovarian cancer. METHODS: This presentation is based on systematic literature search in Pubmed, Medline, Cochrane and Internet addresses for treatment protocols. RESULTS: Major controversies still exist on what constitutes optimal surgical staging in a patient with early-stage ovarian cancer and what is optimal surgical management for high-risk patients. Several large retrospective studies consistently identify the size of the largest residual disease after primary cytoreductive surgery as an independent determinant of prognosis, but the size limit of residual disease that needs to be fulfilled for cytoreduction to have effect on survival is not identified. The effect of neoadjuvant chemotherapy in advanced ovarian cancer is uncertain. A large prospective randomized study is initiated for assessing the role of neoadjuvant chemotherapy. The survival rate is better for patients treated at teaching hospitals compared with non-teaching hospitals. CONCLUSION: This systematic review demonstrates the need for more studies on survival outcomes for all surgical treatment methods of primary ovarian cancer assessed in this report.

Randomized intergroup trial of cisplatin-paclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: three-year results.

BACKGROUND: A randomized trial conducted by the Gynecologic Oncology Group (GOG, study #111) in the United States showed a better outcome for patients with advanced ovarian cancer on the paclitaxel-cisplatin regimen than for those on a standard cyclophosphamide-cisplatin regimen. Before considering the paclitaxel-cisplatin regimen as the new "standard," a group of European and Canadian investigators planned a confirmatory phase III trial. METHODS: This intergroup trial recruited 680 patients with broader selection criteria than the GOG #111 study and administered paclitaxel as a 3-hour instead of a 24-hour infusion; progression-free survival was the primary end point. Patient survival was analyzed by use of the Kaplan-Meier technique. Treatment effects on patient survival were estimated by Cox proportional hazards regression models. All statistical tests were two-sided. RESULTS: The overall clinical response rate was 59% in the paclitaxel group and 45% in the cyclophosphamide group; the complete clinical remission rates were 41% and 27%, respectively; both differences were statistically significant (P =.01 for both). At a median follow-up of 38.5 months and despite a high rate of crossover (48%) from the cyclophosphamide arm to the paclitaxel arm at first detection of progression of disease, a longer progression-free survival (log-rank P =.0005; median of 15.5 months versus 11.5 months) and a longer overall survival (log-rank P =. 0016; median of 35.6 months versus 25.8 months) were seen in the paclitaxel regimen compared with the cyclophosphamide regimen. CONCLUSIONS: There is strong and confirmatory evidence from two large randomized phase III trials to support paclitaxel-cisplatin as the new standard regimen for treatment of patients with advanced ovarian cancer.

DNA copy number changes in malignant ovarian germ cell tumors.

Malignant ovarian germ cell tumors (OGCTs) include immature teratomas (ITs), dysgerminomas (DGs), endodermal sinus tumors (ESTs), choriocarcinomas, and embryonal carcinomas. Knowledge about the genetic changes associated with malignant OGCT development is sparse. We therefore analyzed 25 OGCTs (12 DGs, 4 ESTs, and 9 ITs) for gains and losses by comparative genomic hybridization. In total, more gains than losses were observed, and the number of alterations ranged from 0-20 per tumor. The average number of changes among DGs, ESTs, and ITs was 10, 6, and 1.4, respectively. The most common changes in DGs were gains from chromosome arms 1p (33%), 6p (33%), 12p (67%), 12q (75%), 15q (42%), 20q (50%), 21q (67%), and 22q (58%); gains of the whole of chromosomes 7 (42%), 8 (42%), 17 (42%), and 19 (50%); and losses from 13q (58%). Two of three DGs with a gonadoblastoma component showed gains of 3p21 and loss of 5p, whereas none of the nine pure DGs had these changes, suggesting that they might be characteristic either of gonadoblastoma or of DG developing from a gonadoblastoma. Gain of 12p and gain from 1q were seen in three of four ESTs, whereas gains from 3p, 11q, and Xp and loss from 18q were each found in two tumors. Five of the ITs revealed changes (range, 1-4 changes/tumor), with gains from 1p, 16p, 19, and 22q each being found in two tumors. We conclude that ovarian DGs and ESTs seem to develop via the same genetic pathways that are already known for testicular germ cell tumors. On the other hand, ITs do not exhibit gain of 12p and also typically show fewer changes than other malignant OGCTs, indicating that they arise via different pathogenetic mechanisms.

Paclitaxel- and docetaxel-dependent activation of CA-125 expression in human ovarian carcinoma cells.

Taxanes represent a new class of antineoplastic agents that are being evaluated in several malignant tumors; they have been shown to induce a high remission rate and to prolong survival in ovarian cancer patients. However, CA-125 has been suggested to be an unreliable marker for monitoring response to paclitaxel therapy. Therefore, we were interested in whether taxanes may directly modulate CA-125 expression. Human ovarian carcinoma cell lines OVCAR-3, HOC-7, SKOV-6, 2780, 2774, and HTB-77 were treated with paclitaxel or docetaxel. Secreted, surface-associated, and cytosolic CA-125 were estimated by means of a sandwich solid-phase RIA or by immuno-flow cytometry. In addition to in vitro antiproliferative activity, paclitaxel and docetaxel augmented the expression of the tumor marker CA-125 in the three ovarian carcinoma cell lines, OVCAR-3, HOC-7, and SKOV-6, constitutively expressing this tumor marker. The three CA-125-negative cell lines, 2780, 2774, and HTB-77, did not respond to taxane treatment by expressing this tumor marker, although their proliferation was markedly inhibited. The taxane-mediated induction of CA-125 was found to be dependent on intact protein and RNA biosynthesis. However, CA-125 concentration was increased in the supernatant medium only and not on cell surface or cytosol. Our results demonstrate an in vitro activation of ovarian carcinoma cells in terms of CA-125 secretion by taxanes. This may explain the CA-125 fluctuations observed in vivo under paclitaxel treatment and may indicate that CA-125 is not a reliable tumor marker during taxane chemotherapy.

Symptoms and referral of women with epithelial ovarian tumors.

OBJECTIVE: To study referral to hospital units and the clinical characteristics of women with epithelial ovarian tumors in a prospective, population-based study. METHODS: Clinical information on all women diagnosed with epithelial invasive (n=486) and borderline ovarian tumors (n=137) in Norway during 2002 was derived from notifications to the Cancer Registry of Norway and medical, surgical and histopathological records. RESULTS: Sixty-one percent of women with invasive ovarian tumors were initially referred to gynecology units. The 38% of women referred to surgical and medical units were more likely to have symptoms as 'bowel irregularity', 'pain outside the abdominal cavity', 'persisting fatigue' and 'respiratory difficulties'. These women were older, had lower performance status and had a delay in treatment of 20 and 24 days respectively compared to 11 at gynecology units. CONCLUSION: Greater awareness of the symptoms of ovarian cancer might lead to earlier diagnosis and treatment and thus possibly improve survival.

Tamoxifen in the treatment of recurrent ovarian carcinoma.

This review examines the evidence for useful clinical activity of tamoxifen in women with ovarian carcinoma who have failed conventional cytotoxic chemotherapy. The optimised search strategy of the Cochrane Gynaecological Cancer Collaborative Review Group by Williams was used. Tamoxifen demonstrates a modest degree of effectiveness in ovarian cancer refractory to cytotoxic chemotherapy. The overall objective response rate in all trials (647 patients) was approximately 11%. There is, however, a wide variation in the objective response rates in the different trials (0-56%). Tamoxifen therapy has limited efficacy in refractory ovarian carcinoma. However, considering the mild toxicity of tamoxifen, occasional long-term palliation and lack of alternatives, the drug has a useful role in heavily pretreated patients with ovarian cancer.

Human papilloma virus has no prognostic significance in cervical carcinoma.

The prognostic significance of the detection of HPV (human papilloma virus) DNA in cervical carcinoma was evaluated in 223 cases treated from January 1988 to November 1989. HPV DNA was detected by PCR (polymerase chain reaction) on fresh tumour specimens obtained before therapy was started. HPV DNA of any type was detected in 93.3% of all tumours, HPV16 was the predominant type and was detected in 69% of cases. HPV18 was more frequent in adeno- and adenosquamous carcinoma than in squamous cell carcinoma and occurred more often in poorly differentiated tumours than in more highly differentiated tumours. Patients with HPV negative tumours were on average older than patients with tumours containing HPV. Neither presence of HPV DNA nor HPV type had prognostic significance. In 63 women with early stage tumours submitted to surgery, no difference was found in the frequency of lymph node metastasis, vessel invasion or prognosis related to HPV type. We conclude that neither the presence nor the type of HPV DNA had any prognostic significance in cervical carcinoma.

Management of borderline tumors of the ovary: state of the art.

Evidence published during several decades has shown that there is a group of epithelial ovarian tumors having histological and biological features between those of clearly benign and frankly malignant tumors. In 1963, FIGO accepted an intermediate group of ovarian carcinomas of low malignant potential. In 1973, WHO adopted the term borderline malignancies to describe these tumors. Borderline tumors represent approximately 10% to 15% of all epithelial ovarian malignancies. There are considerable discrepancies in the reported incidence of ovarian tumors of borderline malignancies. Some centers do not recognize tumors of this type and include them among invasive cancers. The prognosis for patients with borderline tumors is generally considered to be excellent. Although the standard treatment for older patients is abdominal hysterectomy and bilateral salpingo-oophorectomy, many young patients who have not completed childbearing can be safely treated with unilateral salpingo-oophorectomy coupled with comprehensive surgical staging, thereby preserving fertility potential. Even ovarian cystectomy has been reported, but the recurrence rate in the ovary approximates 15%. Many experts strongly believe that surgery is the only effective treatment for borderline tumors. Others routinely use postoperative chemotherapy for at least some subsets of patients with peritoneal implants. Currently, insufficient information is available to make a definitive statement regarding the efficacy of postoperative therapy. Nevertheless, clinicians are faced with the difficult task of making treatment recommendations to anxious patients. In the past, extensive application of automated methods for analytical cytology has resulted in large quantities of data on ploidy abnormalities in different types of human cancers. The main purpose has been to obtain additional parameters for the characterization of various types of malignancy to give more precise information on their biological behavior. Data from the Norwegian Radium Hospital showed that the majority of borderline tumors have DNA diploid tumors and good prognosis, DNA aneuploidy indicates high risk. Several other investigators have shown the same results on DNA ploidy as a predictor of recurrence and survival, but a few others have shown conflicting results. Early studies suggest that p53 mutation does not appear to play a role in the pathogenesis of these tumors. Studies on other molecular markers have not yet uncovered a reliable predictor of biologic behavior. However, it is hoped that future studies of genetics and molecular biology of these tumors will lead to useful laboratory tests.

Comparison of HPV detection in parallel biopsies and cervical scrapes by PCR.

PCR was used to detect HPV DNA in cervical scrapes of 23 women with cervical cancer. Compared with PCR-assisted HPV DNA detection in parallel biopsies, the sensitivity was 81% and the specificity 100%. We conclude that cervical scrapes can be used for detection of HPV DNA in women with cervical cancer.

Human papillomavirus infection in Norwegian women with cervical cancer.

The objective of the present study was to determine the prevalence of human papillomavirus (HPV) infections in Norwegian women with cervical cancer. We used the polymerase chain reaction (PCR) and Southern blot techniques to assess the prevalence of HPV in cervical biopsies of 133 women admitted to the Norwegian Radium Hospital for treatment of cervical cancer. At the time of sampling (from February 1988 to April 1989) about 85% of Norwegian women with cervical cancer were treated at the Norwegian Radium Hospital. HPV was found in biopsies of 91 (68%) of women with cancer; 70 (53%) biopsies contained HPV type 16, 19 (14%) HPV type 18, 4 (3%) HPV type 33, 2 (1.5%) HPV type 11, and 3 (2%) HPV DNA of unknown type (HPVX). Five percent of biopsies were doubly infected, chiefly with HPV 16 + 18. We found a significant association between HPV 18 and low age, poorly differentiated tumors and adenocarcinomas. Our results show that there is an association between HPV types 16 and 18 and cervical cancer also in a Norwegian setting. PCR was more sensitive than Southern blotting for detection of HPV. Thirty-six (27.5%) of cancer biopsies were positive by PCR but negative by Southern blotting, as against 49 (73.5%) positive by both methods; we also encountered 4 samples positive by Southern blotting and negative by PCR. In 23/53 cancer biopsies positive by Southern blotting we found evidence for integrated or rearranged HPV genomes.

Intrauterine growth in twin pregnancies: prediction of fetal growth retardation.

In 80 consecutive twin pregnancies, prenatal measurements of fetal biparietal diameter (BPD) and abdominal diameter were made and growth curves were calculated using routine ultrasound examinations. Nineteen percent of the infants were growth retarded. Growth retardation was found in both fetuses in four pregnancies and in one fetus in 22 other pregnancies. Linear regression analysis between birth weight and gestational age showed the standard deviation of birth weight to be proportional to gestational age. A more linear growth curve also was found when the mean fetal weight was calculated by use of the BPD and abdominal diameter measurements in the formula developed for singletons. The estimated weight compared with birth weight in 62 twins who had ultrasound examinations less than seven days before delivery showed a significant correlation (r = 0.89, P less than .001) with a coefficient of variation of 12.4%. The identification of intrauterine growth retardation (IUGR) in twin pregnancies by ultrasound had a sensitivity of 62%, a specificity of 98%, and a predictive value of positive and negative test of 93% and 83%, respectively.

Prognostic value of pre- and postoperative serum CA 125 levels in ovarian cancer: new aspects and multivariate analysis.

The prognostic significance of the serum CA 125 level was studied in 687 patients with invasive epithelial ovarian malignancies. The samples were collected preoperatively in 200 and postoperatively in 487 patients. Median follow-up was 27 months (range 3-84). The serum CA 125 level was elevated preoperatively in 90% of cases, with a median value of 429 U/mL. In patients with evidence of disease at the time of sampling, the CA 125 serum level correlated directly to tumor stage, tumor load, and histologic grade. Using Cox multivariate analysis, the preoperative serum CA 125 level had no independent prognostic significance, whereas the postoperative level did. In patients without residual disease after primary surgery, histologic type (P less than .0001), postoperative CA 125 level with 35 U/mL as the cutoff value (P = .0009), and tumor grade (P = .034) were independent prognostic factors for survival. For those with residual tumor after primary surgery, histologic type (P less than .0001), postoperative treatment (P = .0002), size of residual disease (P = .0005), and postoperative serum CA 125 level with 65 U/mL as a cutoff (P = .003) were independent prognostic factors.