Early tumor regrowth is a contributor to impaired survival in patients with completely resected advanced ovarian cancer. An exploratory analysis of the Intergroup trial AGO-OVAR 12.

OBJECTIVE: Surgical assessment of residual tumor provides the strongest prognostic information in advanced ovarian cancer (AOC), with the best outcome observed after complete resection. Postoperative radiological assessment before initiation of chemotherapy can supplement the information obtained by surgical assessment; however, it may also reveal conflicting findings. METHODS: Patients with AOC enrolled in the AGO-OVAR 12 trial underwent baseline imaging before the first chemotherapy cycle. The findings from surgical and radiologic assessment for disease extend were compared. Additionally, an integrated approach was assessed. RESULTS: Complete data from all 3 assessment methods were available for 1345 patients. Of 689 patients with complete resection, tumor was observed in 28% and 22% of patients undergoing radiologic and integrated assessment, respectively. Patients with surgical- radiological and surgical-integrated concordant findings showed a 5-year overall survival (5Y-OS) of 72% and 71%, whereas patients with surgical-radiological and surgical-integrated discordant results showed inferior 5Y-OS of 47% and 49%, respectively. Patients with surgically assessed residual disease had a 5-YOS of 37%. The interval between surgery and baseline assessment was independently associated with discordance between assessment methods, which might reflect early tumor regrowth. CONCLUSIONS: Baseline tumor assessment before chemotherapy provides information that stratifies patients with complete resection into different prognostic groups. Integrating the data from different assessment methods might lead to improved definitions of prognostic groups. Further investigation to determine if earlier initiation of chemotherapy after debulking surgery could increase survival of patients with early tumor regrowth is warranted.

Prognostic role of CIP2A expression in serous ovarian cancer.

BACKGROUND: Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein expressed in several solid cancers. Our purpose was to study its role in serous ovarian cancer patients, and the association to clinicopathological variables and molecular markers. METHODS: We collected retrospectively 562 consecutive serous ovarian cancer patients treated at the Helsinki University Central Hospital. We stained tumour tissue microarrays for CIP2A by immunohistochemistry and constructed survival curves according to the Kaplan-Meier method. Associations to clinicopathological and molecular markers were assessed by the χ(2)-test. RESULTS: We found strong cytoplasmic CIP2A immunoreactivity in 212 (40.4%) specimens, weak positivity in 222 (42.4%) specimens, and negative in 90 (17.2%). Immunopositive CIP2A expression was associated with high grade (P<0.0001), advanced stage (P=0.0005), and aneuploidy (P=0.001, χ(2)-test). Cancerous inhibitor of protein phosphatase 2A overexpression was also associated with EGFR protein expression (P=0.006) and EGFR amplification (P=0.043). Strong cytoplasmic CIP2A immunopositivity predicted poor outcome in ovarian cancer patients (P<0.0001, log-rank test). CONCLUSION: Our results show that CIP2A associates with reduced survival and parameters associated with high grade in ovarian cancer patients, and may thus be one of the factors that identify aggressive subtype (type II) of this disease.

Past chlamydial infection is not associated with primary fallopian tube carcinoma.

We conducted a retrospective seroepidemiological study to evaluate the relationship between past chlamydial infection and primary fallopian tube carcinoma (PFTC). Postoperative serum samples were drawn from 79 consecutive patients treated for PFTC in 1985-2000. For each case two controls were selected. Serum samples were analysed for IgG antibodies to different C. trachomatis serotype pools and to C. pneumoniae. Seropositivity in general or serum antibody levels to different C. trachomatis serovars or C. pneumoniae did not differ between PFTC patients and controls. The lack of association between anti-chlamydial antibodies and PFTC suggests that past chlamydial infection does not play a role in the etiopathogenesis of PFTC. However, because chlamydial infection is common at young age and PFTC develops decades later, we cannot definitively exclude the possibility that C.trachomatis contributes to the development of PFTC.

Epidemiology of hydatidiform mole in Finland, 1975 to 2001.

PURPOSE: Broad variations in the incidence of gestational trophoblastic diseases have been reported in different parts of the world. Recent time trends in the incidence of hydatidiform mole in Western countries have not been elucidated. We studied the epidemiology of hydatidiform mole in Finland over a period of 27 years. METHODS: Women reported to have hydatidiform mole from 1975-2001 were identified from the National Research and Development Center for Welfare and Health. Women with choriocarcinoma were identified from the Finnish Cancer Registry. RESULTS: We identified 1659 cases of hydatidiform mole between 1975 and 2001. This gives an incidence of 73/10(6) women or 984/10(6) deliveries. The overall incidence remained fairly constant over the study period. The incidence was higher in women below 20 years and above 39 years than in women in the other age groups. Forty-nine percent of choriocarcinomas identified during the study period were associated with a preceding hydatidiform mole. The risk of choriocarcinoma after a hydatidiform mole was 2.2%. CONCLUSIONS: The incidence of hydatidiform mole in Finland follows the same patterns as in other Western countries. The incidence has not changed considerably in recent decades.

Human papillomavirus types 16 and 18 in adenocarcinoma of the uterine cervix.

Many reports have shown a link between human papillomavirus (HPV) and cervical squamous neoplasia. However, the association of HPV with cervical adenocarcinoma has been studied less extensively. The authors evaluated the presence of HPV-DNA in 106 patients with adenocarcinoma of the uterine cervix by in situ hybridization, using 35S-labeled probes for HPV 16 DNA and HPV 18 DNA. The overall prevalence of HPV-DNA was 18% (19 of 106). HPV 16 was present in 2 (2%) cases, HPV 18 was observed in 15 (14%) cases, and both HPV 16 and HPV 18 were found in 2 (2%) cases. There was a correlation between HPV-DNA positivity and tumor stage (P less than 0.01) and tumor size (P less than 0.05), but there was no relationship between HPV-DNA positivity and tumor differentiation, proliferation (S-phase fraction), ploidy, lymph node metastases, or five-year survival rate. These results suggest that HPV 18 DNA is associated with cervical adenocarcinoma but the presence of HPV 18 has no influence on overall survival.

Predominance of serum antibodies to synthetic peptide stemming from HPV 18 open reading frame E2 in cervical adenocarcinoma.

AIMS: To determine if there are type specific differences in serum antibody responses to synthetic peptides derived from human papillomavirus (HPV) open reading frame (ORF) E2 in patients with cervical carcinoma. METHODS: Diagnostic phase sera from 88 age-matched women with cervical adenocarcinoma (AC), cervical squamous cell carcinoma (SC), ovarian cancer (OC) or no gynaecological malignancy were available. Serum IgG and IgA antibodies to synthetic peptides corresponding to a residue of HPV 6, 11, 16, and 18 ORF E2 18 amino acids long and a control peptide from mumps virus were determined by ELISA. RESULTS: Both IgA and IgG antibody positivity to the HPV 18 peptide were associated with increased risk (9.0-fold, confidence limits 1.5-199) for AC. IgA positivity to HPV 11, 16, and 18 peptides was associated with an increased risk for SC. However, the association of IgG antibodies to HPV 16 peptide with SC was not significant. IgA or IgG antibodies to HPV 6 or mumps virus peptides were not associated with increased risk for AC, SC, or OC. CONCLUSIONS: These results suggest a specific role for HPV 18 in AC. Differences in antibody responses to HPV peptide in AC and SC suggest immunopathogenetic differences between the two types of cervical carcinoma.

Transvaginal sonographic findings in ambulatory patients with suspected pelvic inflammatory disease.

OBJECTIVE: To evaluate transvaginal sonographic findings in ambulatory patients with suspected pelvic inflammatory disease (PID). METHODS: We studied 51 outpatients with a mean age of 26.8 years (range 16-52) who had a history of low abdominal pain, negative pregnancy test, and no gynecologic procedures performed during the last month. Endometrial biopsy was used for the histopathologic diagnosis. The presence of plasma cell endometritis was used as the criterion standard for the diagnosis of PID. Sonography was performed before biopsy in a blinded fashion without knowledge of the clinical findings and laboratory results except for the pregnancy test. Repeat pelvic and ultrasound examinations were performed 4 weeks after antimicrobial therapy. RESULTS: Endometrial biopsy revealed plasma cell endometritis in 13 cases (25%). Thickened fluid-filled tubes were seen in 11 of 13 patients (85%) with plasma cell endometritis and in none of those without. Other sonographic findings associated with plasma cell endometritis were polycystic-like ovaries and free pelvic fluid. A sonogram suggestive of PID, ie, thickened fluid-filled tube with or without free pelvic fluid, had a sensitivity of 85% and a specificity of 100% for the diagnosis of plasma cell endometritis. None of the patients with a normal sonogram or simple cyst had plasma cell endometritis. Repeat examination after 4 weeks showed that the sonographic findings had resolved in 60% of the patients who had had histologic evidence of infection. CONCLUSION: Transvaginal sonography can facilitate the outpatient management of patients with suspected PID.

Wound complications in patients with carcinoma of the vulva. Comparison between radical and modified vulvectomies.

OBJECTIVE: To evaluate complications after different vulvectomies performed because of vulvar cancer. STUDY DESIGN: Retrospective analysis of 149 patients who underwent vulvectomy. RESULTS: Wound infections was found in 58%. Overweight, central or bilateral location of the tumor, and non-radical surgery were significant predictors of wound infections. Patients with a wound infection had more often wound breakdown (P<0.001), prolonged healing time (P<0.000), and lymphedema (P<0.001) than patients without infection. Antimicrobial prophylaxis did not prevent wound infection. Wound infections were found in 75% after radical en bloc vulvectomy (RV) and in 47% after modified vulvectomies (MV) (P<0.001). Also wound breakdown (47 versus 20%) (P<0.001) and lymphedema (48 versus 12%) (P<0.0001) were more common in RV group than in MV group. Lymphocysts were found in 7%, and showed no association with wound infection or type of operation. The mean hospital stay was 26 days in patients with wound infection and 12 days in patients without infection, 31 days in RV group and 12 days in MV group, respectively. CONCLUSIONS: Wound infections are major determinants for both acute and late complications. Postoperative complications reduce with increasing use of modified vulvectomies.

Incidence of uterine leiomyosarcoma and endometrial stromal sarcoma in Nordic countries: results from NORDCAN and NOCCA databases.

OBJECTIVES AND STUDY DESIGN: Uterine sarcomas are an uncommon and heterogeneous group of malignancies. Their etiology is mainly unknown. Here, we analyzed trends in incidence and occupational variation in risk of uterine leiomyosarcomas (LMS) and endometrial stromal sarcomas (ESS) in the Nordic countries aided by NORDCAN and NOCCA (Nordic Occupational Cancer) databases. MAIN OUTCOME MEASURES: Incidence rates per 100,000 and Standardized incidences rates (SIR) obtained from NORDCAN and NOCCA databases. RESULTS: The incidence rates were about 0.3 per 100,000 for ESS and about 0.4 per 100,000 for LMS in Denmark, Finland, Iceland, and Norway. During the study-period (1978-2007), the incidence rates in each country were quite similar and constant. The age-specific incidence of LMS showed a peak around menopause. Significantly increased risk for LMS occurred in shoe and leather workers, farmers and teachers, whereas significantly low risk was detected with packers in the NOCCA data from Finland, Norway, and Sweden. For ESS no occupations showed either increased or decreased incidences. CONCLUSIONS: The incidence trends of LMS and ESS in our study were constant in four Nordic countries over time. The elevated risk for LMS with women exposed to leather work and animal dust indicates further exploration.

Human papillomavirus infection and primary fallopian tube carcinoma: a seroepidemiological study.

OBJECTIVE: To evaluate the role of human papillomavirus (HPV) types 6, 11, 16, 18, 31 or 33 infection in primary fallopian tube carcinoma (PFTC). DESIGN: A retrospective case-control study. SETTING: Department of Obstetrics and Gynaecology, Helsinki University Hospital, Finland. POPULATION: Seventy-eight consecutive women with PFTC diagnosed between 1985 and 2000 were studied. For each case, two healthy controls were selected. METHODS: Serum immunoglobulin G antibodies to HPV types 6, 11, 16, 18, 31 and 33 were measured from women with PFTC and their healthy controls. MAIN OUTCOME MEASURES: Analysis of HPV 6, 11, 18, 31 and 33 seropositivity among women with PFTC and controls. RESULTS: Seropositivity rates of non-oncogenic or oncogenic HPV types did not differ between cases and controls, odds ratios being 1.04-1.30 for oncogenic HPVs and 1.08-1.19 for non-oncogenic HPVs, similarly. We did not find any multiplicative joint effect in PFTC by antibodies to more than one oncogenic HPV type; neither did we find any antagonistic effect among women with antibodies to non-oncogenic and oncogenic HPV types. CONCLUSIONS: Our results do not suggest any link between PFTC and serological evidence for HPV infection.

Preoperative serum hCGbeta as a prognostic marker in primary fallopian tube carcinoma.

OBJECTIVES: It was the aim of this study to evaluate the prognostic value of the pretreatment serum concentrations of the beta-subunit of human chorionic gonadotropin (hCGbeta), CA 125 and tumour-associated trypsin inhibitor (TATI) in primary fallopian tube carcinoma (PFTC). METHODS: The pretreatment serum concentrations of hCGbeta, CA 125 and TATI were analyzed in serum samples from 60 women with a mean age of 61 years, treated for PFTC between 1985 and 2000. Of the 91 patients treated during this period, 31 were excluded because no serum sample was available. The patients were followed-up for recurrence and survival until February 14, 2003. The prognostic value of the serum markers were compared with those of stage, grade and histological type. RESULTS: The median survival time was 27 months and the overall 5-year survival rate 33%. Stage and size of the residual tumour (<1 vs. > or =1 cm) predicted both overall and disease-free survival (p < 0.050). Histology (serous vs. others) (p = 0.023) also influenced overall survival. Overall 5-year survival was 38% when serum hCGbeta was below 3.5 pmol/l, while it was 18% when the level was higher (p = 0.052). The corresponding disease-free 5-year survival was 38 and 20%, respectively (p = 0.014). Patients with CA 125 values above 1,017 kU/l had an overall 5-year survival of 39% as compared with 14% for those with lower values (p = 0.009), while the disease-free survival was 37 and 23%, respectively (p = 0.096). Serum TATI was not a prognostic marker. Serum concentrations of hCGbeta and CA 125 correlated significantly with stage (p = 0.049 and p = 0.050, respectively). In multivariate Cox proportional hazards regression analysis, only hCGbeta, stage and histology emerged as independent prognostic factors. CONCLUSIONS: Clearly elevated serum concentrations of hCGbeta and CA 125 predict survival in fallopian tube carcinoma, but in multivariate analyses, only hCGbeta is a prognostic factor independent of stage and histology.

Comparison between personal learning curves for abdominal and laparoscopic hysterectomy.

BACKGROUND: To compare personal learning curves for abdominal and laparoscopic hysterectomy. METHODS: The first 200 patients scheduled for abdominal hysterectomy and the first 200 patients scheduled for laparoscopic hysterectomy by a single operator were compared using learning curves according to operation time, operative blood loss, and occurrence of complications. RESULTS: Learning curves for both types of hysterectomy were rather similiar, but the learning of the laparoscopic procedure seemed to be quicker. With increasing experience the operating time decreased by 25% in abdominal and by 41% in laparoscopic hysterectomies. The mean operating time in abdominal hysterectomy was 74 min and 70 min in laparoscopic hysterectomy. Operative blood loss decreased by 50% and 44%, respectively. The mean operative blood loss was smaller (203 vs 295 ml, p<0.0001) in laparoscopic hysterectomy. Increased experience had no effect on complication rates in abdominal hysterectomies, but a decrease of 44% was seen in laparoscopic hysterectomies (p<0.05). The overall complication rate (26% vs 22%) were similar for the two techniques, and only a few patients (1.5% vs 1%) had major (bladder or ureteric) complications. CONCLUSIONS: A trained gynecologist can learn the laparoscopic technique for hysterectomy at least as quickly as the abdominal technique.

Tumor markers CA 125, carcinoembryonic antigen and tumor-associated trypsin inhibitor in patients with cervical adenocarcinoma.

Tumor markers CA 125, carcinoembryonic antigen (CEA) and tumor-associated trypsin inhibitor (TATI) were studied in 42 patients with cervical adenocarcinoma. Pretreatment levels of CA 125 were elevated in 73% of 33 patients, CEA in 48% of 27 patients, serum TATI in 23% of 22 patients, and urine TATI in 38% of 26 patients. Elevated CA 125 levels were associated with histological grade (P = 0.002), and elevated CEA levels with the presence of lymph node metastases (P = 0.008), respectively. No associations were found between elevated tumor marker levels and stage, or tumor size. Serum CA 125 levels increased in 71% of the patients with progressive disease, CEA levels in 36%, serum TATI levels in 46%, and urine TATI levels in 20% of the patients. In all patients with regressive disease the tumor marker levels decreased or stayed unchanged. Regression of the disease was significantly correlated (P less than 0.05) with stage, histological grade, tumor size, and nodal status. The results suggest that CA 125 and, to a lesser extent, CEA and TATI are useful in the follow-up of patients with cervical adenocarcinoma.

Spread of ovarian cancer after laparoscopic surgery: report of eight cases.

OBJECTIVE: The aim of this study was to describe early occurrences of metastases after laparoscopy of ovarian masses later found to be malignant. METHODS: The hospital charts of eight women having undergone laparoscopic surgery for ovarian mass were reviewed and analyzed. RESULTS: The mean age of the patients was 40 years (range 25 to 66). Size of the tumor ranged from 2 to 15 cm. In four patients the ovarian mass was suspected to be malignant in the laparoscopy. Diagnostic procedure (biopsy of the tumor) was performed in two and salpingo-oophorectomy in six patients. Staging laparotomy was performed within the mean of 17 days (range 7-29). In four patients (50%) the cancer had spread from a localized to an advanced stage during the delay. Ascites was present in the laparoscopy in two of the four patients with port site or abdominal wall metastases. CONCLUSIONS: Laparoscopic surgery of ovarian mass later found to be malignant can cause considerable and early spread of the cancer.

Strategies for improving compliance in hypertensive patients.

The results of the present trial, aimed at elucidating and improving the treatment situation of hypertensives, show that--within the domain of the Finnish community health centres--it continues to be unsatisfactory. The prevalence of the male hypertensives (those without treatment and with a permanent diastolic pressure level of at least 100 mmHg and those under treatment) aged 35 to 49 years, was 12.8%. Only half of them were receiving treatment and of these the treatment was adequate (diastolic pressure less than 90 mmHg) in only one case out of five. Overweight turned out to be common among hypertensives, 63.2% of them had at least 10% overweight (BMI greater than or equal to 27.0 kg/m2) while 15.7% had at least 30% overweight (BMI greater than or equal to 32.0 kg/m2). There were no differences worth noting in overweight between treated and untreated cases. With respect to tobacco smoking there was a clear difference in favour of the hypertensives receiving treatment, among whom only 26.1% were regular smokers, while the corresponding figure for untreated hypertensives were 41.7%. Within short time an improved, supervising physician-based treatment system could be seen to have led to favourable results in the treatment of hypertensive community health centre patients. The proportion of those receiving adequate treatment among subjects already under treatment prior to the screening, for instance, had become threefold within a few months.