A comparison between ultrasonography and hysteroscopy in the diagnosis of uterine pathology

Objective

To evaluate the diagnostic accuracy of transvaginal sonography (TVS) compared to hysteroscopy in diagnosing uterine abnormalities. In addition, to determine whether the number of diagnostic hysteroscopies can be reduced and replaced by TVS examinations.

Study design

In this retrospective study, we summarized data from 128 patients who underwent TVS examination and hysteroscopy in our ultrasound unit during the last two years. Specimens were obtained and sent for histopathological examination. Sensitivity, specificity, positive and negative predictive values for diagnosing uterine pathology were calculated for each method.

Results

Hysteroscopy had a significantly higher sensitivity in diagnosing intra-uterine fibroids while TVS had a significantly higher sensitivity in diagnosing retained products of conception. Although hysteroscopy had better predictive values for diagnosing uterine polyps the difference was not statistically significant. The combination of both TVS and hysteroscopy did not seem to improve the sensitivity and specificity. There were three additional important findings: two cases of uterine hyperplasia and one case of endometrial carcinoma in patients with abnormal uterine bleeding were all diagnosed by hysteroscopy after being suspected on the TVS examination.

Conclusion

TVS is an excellent tool in evaluating retained products of conception. In other cases of uterine pathology, diagnostic hysteroscopy is needed to improve diagnostic accuracy.     

Use of ovarian reserve parameters for predicting live births in women undergoing in vitro fertilization

Objective

To examine common clinical determinants, including patient age; levels of anti-Müllerian hormone (AMH), inhibin B, and follicle-stimulating hormone (FSH); antral follicle count (AFC); and number of oocytes retrieved, to predict live births in women undergoing in vitro fertilization.

Study design

Women undergoing cycles of intracytoplasmic sperm injection (ICSI) for the first time were reviewed retrospectively, and serum levels of AMH, inhibin B, and FSH, as well as AFC (days 1 and 4 of pre-ICSI menstrual period) and patient age were analyzed as determinants of live birth rates.

Results

Of the patients studied, 35.71% (891/2495) became pregnant, with live births achieved in 32.20% (806/2495) of cycles initiated and in 46.37% (806/1738) of embryo transfers. Clinical pregnancy rate was 35.71% (891/2495) for cycles initiated and 51.26% (891/2318) for embryo transfers. Univariate analysis revealed that the odds of live birth significantly decreased with increasing age, declining AMH or inhibin B concentrations, and fewer oocytes retrieved. At AMH levels greater than 5.7 ng/ml, the odds of live birth were 3.18 times greater than for AMH levels less than 1.9 ng/ml [95% confidence interval (CI), 1.89–5.43]. Using multivariate logistic regression, only AMH (OR = 1.89; 95% CI, 1.00–3.60; p < 0.05) and AFC (OR = 1.86; 95% CI, 1.02–3.40; p < 0.05) showed statistically significant associations with live birth. Area under the curve for ROC (ROC_AUC) indicated that AMH (AUC = 0.60) surpassed AFC (AUC = 0.59), number of oocytes retrieved (AUC = 0.59), inhibin B (AUC = 0.55), FSH (ROC_AUC = 0.54) and chronological age (ROC_AUC = 0.53) in predicting live birth.

Conclusions

In this assessment of various indices (i.e., age; levels of AMH, inhibin B, and FSH; AFC; and quantity of oocytes retrieved) for predicting live births for IVF patients, AMH, AFC and the quantity of oocytes retrieved constituted the most reliable determinants.     

A predictive model combining human epididymal protein 4 and radiologic features for the diagnosis of ovarian cancer

Objective

Ovarian cancer is the leading cause of death in women with gynecologic cancer. CA125 is the commonly used biomarker in the diagnosis of ovarian cancer, but has limitations in both sensitivity and specificity. Human Epididymal secretory protein (HE4) is a promising biomarker and is included in the Risk of Ovarian Malignancy Algorithm (ROMA) score, which is suggested to further increase the diagnostic accuracy than either marker alone. However, information from ultrasound and CT-scan is not included in this algorithm. This study evaluated the diagnostic accuracy of HE4 in the pre-operative diagnosis of ovarian cancer and the predictive values of biomarkers, ultrasound and CT-scan and combinations hereof.

Methods

HE4 and CA125 were measured in 361 subjects (34 benign, 147 ovarian cancer and 180 controls). Sensitivity, specificity and area under the curve (AUC) for CA125, HE4, ROMA and RMI scores were calculated using the receiver operating characteristic (ROC) methodology. The additional predictive value of ultrasound or CT-scan to the individual markers was analyzed using logistic regression.

Results

The sensitivity in predicting ovarian cancer of CA125 was 91% and of HE4 90%. The specificity was 65% and 97% respectively. HE4 demonstrated the highest discrimination (ROC-AUC = 0.96), compared to ROMA, RMI and CA125 (AUC = 0.95, 0.89 and 0.90 respectively). ROMA did not improve when it was combined with different ultrasound factors. The presence of intra-abdominal metastasis on CT-scan improved the discriminative potential of HE4 (p = 0.0004).

Conclusion

HE4 in combination with CT-scan may be incorporated in the diagnostic work-up in women with a pelvic mass.     

Premenopausal bleeding: When should the endometrium be investigated?—A retrospective non-comparative study of 3006 women

Objective

There is lack of consensus amongst professional organizations as regards the cut-off age for endometrial sampling of premenopausal women presenting with abnormal uterine bleeding (AUB) to exclude endometrial hyperplasia or carcinoma. Therefore we conducted this study to quantify the prevalence of hyperplasia and carcinoma in different age categories in premenopausal women with AUB to identify the appropriate cut-off age for endometrial sampling.

Study design

A retrospective review of the histopathology reports of endometrial samples taken from 3006 women presenting with AUB and aged from ≥30 to ≤50 years at Ipswich Hospital, UK, from 1 January 1998 to 31 December 2007. Women were divided into three subgroups according to age; group 1: 30 to ≤40 (n = 862), group 2: 40 to ≤45 (n = 1035) and group 3: 45 to ≤50 (n = 1109).

Results

Logistic regression revealed that the prevalence of atypical hyperplasia (OR: 3.85; 95% CI: 1.75, 8.49; p = 0.01) and carcinoma (OR: 4.03; 95% CI: 1.54, 10.5; p = 0.04) was significantly higher in women in group 3 when compared to younger women. There was no statistically significant difference as regards simple and complex hyperplasia in the different age categories. All but one of the women (n = 23) who had complex atypical hyperplasia or carcinoma under the age of 45 years, presented with irregular rather than cyclical heavy menstrual bleeding.

Conclusion

Our study, the largest in the literature, suggests using the age 45 years as a cut-off for sampling the endometrium in all women with AUB. However, irregular menstrual bleeding justifies investigating women regardless of their age.     

Outcomes of ovarian preservation in a cohort of premenopausal women with early-stage endometrial cancer: A Korean Gynecologic Oncology Group study

Objective

The aim of this study was to evaluate the impact of ovarian preservation on the recurrence and survival rates of premenopausal women with early-stage endometrial cancer.

Methods

Using medical records of premenopausal women who received primary surgical treatment for stage I–II endometrial cancer, the demographics and survival rates were compared retrospectively for patients who had ovarian preservation and those who underwent bilateral salpingo-oophorectomy. Cox proportional hazards models with inverse probability of treatment weighting (IPTW) based on propensity score were performed to adjust for selection bias between the two groups.

Results

A total of 495 women were identified, including 176 patients who had ovarian preservation. The ovarian preservation group was younger (P < 0.001) and had an earlier year of diagnosis (P = 0.014), a lower prevalence of lymphadenectomy (P < 0.001), and a marginally significant association with lower tumor grade (P = 0.052). The Kaplan–Meier curve and the log rank test showed no difference in either recurrence-free survival (P = 0.742) or overall survival (P = 0.462) between the two groups. In a multivariate Cox model adjusted by IPTW and covariates, ovarian preservation had no effect on either recurrence (hazard ratio [HR], 0.73; 95% CI, 0.29–1.81) or overall survival (HR, 1.33; 95% CI, 0.43–4.09).

Conclusions

Ovarian preservation does not appear to be associated with an adverse impact on the outcomes of premenopausal women with early-stage endometrial cancer. The present study has useful implications for physicians counseling young women who want to preserve their ovaries.     

Comparison of diagnostic accuracy of saline infusion sonohysterography,transvaginal sonography and hysteroscopy in postmenopausal bleeding

Objective  

To compare the diagnostic accuracy of transvaginal sonography (TVS), saline infusion sonohysterography (SIS) and hysteroscopy (HS) with respect to pathological diagnosis in the detection of uterine cavity abnormalities associated with abnormal uterine bleeding among postmenopausal women.     

Effects of vaginal discharge on female sexual function

Objective

To assess the effects of vaginal discharge on female sexual dysfunction (FSD) by using the Female Sexual Function Index (FSFI).

Methods

In a study at a university hospital in Canakkale, Turkey, women affected by vaginal discharge and age-matched healthy control women were recruited between January and December 2012. Women were grouped in accordance with their vaginal discharge complaints and each participant completed the FSFI questionnaire.

Results

A total of 114 women were included in the study. Women in the first group (n = 58) had no vaginal discharge or had physiologic vaginal discharge, those in the second group (n = 29) had abnormal vaginal discharge with itching, and those in the third group (n = 27) had abnormal vaginal discharge without itching. Compared with the first group, women in the second and third groups had higher FSFI scores for desire, arousal, orgasm, and pain, in addition to higher overall FSFI scores. Women with genital malodor had significantly higher FSFI scores than patients without genital malodor (23.83 ± 5.07 vs 21.15 ± 4.78; P = 0.008).

Conclusion

Women with abnormal vaginal discharges were found to have better FSFI scores for some domains. This finding may be attributed to the adverse effects of sexual intercourse on vaginal infections.     

Venous thromboembolism during primary treatment of ovarian clear cell carcinoma is associated with decreased survival

Objectives

To determine the impact of venous thromboembolism (VTE) during primary treatment of ovarian clear cell carcinoma (OCCC) on survival.

Methods

After Institutional Review Board approval, 74 cases of OCCC were retrieved from our pathology files. Clinical and pathological data were obtained by medical record and pathology review. Standard statistical analyses were performed.

Results

Among 74 patients with OCCC, VTE was diagnosed in 11 (15%) during primary treatment and 7 (9%) at time of cancer recurrence. 56 (76%) patients never developed VTE. Patients with VTE during OCCC primary treatment had shorter progression-free survival (PFS) and overall survival (OS) than OCCC patients without VTE (median PFS 11 vs. 76 months, p = 0.01, median OS 19 vs. 90 months, p = 0.001). Patients with VTE during OCCC primary treatment had a 3.9-fold increase in risk of recurrence (p = 0.007) and a 6.3-fold increase in risk of death (p < 0.001). After controlling for cancer stage, VTE during OCCC primary treatment remained an independent prognostic factor for death (HR = 3.6, p = 0.005). No patient died of VTE.

Conclusions

VTE during OCCC primary treatment is associated with a significantly higher risk of cancer recurrence and death. This increased risk is not attributable to VTE-related mortality and raises the possibility that a paracrine circuit involving thrombosis might contribute to a more aggressive tumor biology.     

Endometrial polyps in obese asymptomatic pre and postmenopausal patients with breast cancer: Is screening necessary?

Objective

To evaluate the prevalence of endometrial polyps in obese asymptomatic pre and postmenopausal patients with breast cancer and to know if a baseline pretamoxifen endometrial assessment should be taken into consideration in these women at high risk.

Methods

A cross-sectional study was carried out with 201 women with breast cancer. A diagnostic hysteroscopy was performed in all women. All formations suspected as polyps were removed. The prevalence of endometrial polyps was analyzed in all patients (n = 182) and in premenopausal (n = 49) and postmenopausal (n = 118) women with estrogen receptor (ER) positive breast cancer (BC) according to their body mass index (BMI) and other risk factors.

Results

Hysteroscopic evaluation was possible in 182 cases (90.5%). Of the total of women, 160 (87.9%) were ER(+)BC patients, 133 (73.1%) postmenopausal women and 41.5% were obese (BMI ≥ 30 kg/m²). Endometrial polyps were found in 52 cases (28.5%) (3 cases of simple hyperplasia harbored within a polyp). In premenopausal patients with ER(+)BC, there were no statistical differences in endometrial polyps according to their BMI (22.3% in non-obese women vs 31.7% in obese) while in all patients (26.4% in non-obese vs 44.0% in obese) and in postmenopausal women with ER(+)BC (25.9% in non-obese vs 48.6% in obese) there were statistical differences. In all women the relative risk (RR) of endometrial polyps in obese patients was 2.24 (1.01–4.83), in obese postmenopausal women with ER(+)BC was 2.75 (1.01–7.40) and in obese premenopausal patients with ER(+)BC was 1.42 (0.80–3.29).

Conclusions

Asymptomatic women with breast cancer have a high prevalence of baseline subclinical endometrial polyps and it is very high in obese postmenopausal patients with estrogen receptor positive breast cancer. Therefore, there may be a future role for baseline pretamoxifen screening of some sort for the obese asymptomatic postmenopausal patient, especially if they are elderly and ER positive.     

Altered CD16 expression on vaginal neutrophils from women with vaginitis

Objective

Reduced CD16 expression is associated with neutrophil apoptosis. This study aimed to compare CD16 expression on neutrophils in the vagina from women with normal bacterial flora and with vaginitis.

Study design

Vaginal lavages were sampled from volunteers diagnosed with bacterial vaginosis (BV, n = 34), vulvovaginal candidiasis (VC, n = 43), BV plus VC (BV + VC, n = 14), and normal flora (NF, n = 51). Neutrophils were identified by expression of CD15, CD16 and CD24 surface markers as assessed by flow cytometry.

Results

CD16 expression was elevated in neutrophils from women with vaginitis (BV p < 0.0001; VC p = 0.01; BV + VC p = 0.0027) as compared to women with NF.

Conclusion

The reduction in CD16 down-regulation is consistent with prolonged neutrophil viability and activity in the vagina of women with vaginitis. This may contribute to greater microbial clearance and, conversely, with inflammation-associated pathology.     

Single incision mid-urethral slings: impact of obesity on outcomes

Objectives

To assess the potential impact of obesity on the success rate of single incision slings (SIS).

Study design

This was a retrospective cohort study of women who underwent the SIS procedure for primary stress urinary incontinence. Women were divided into three different groups by body mass index (BMI) according to the WHO classification. The International Consultation on Incontinence-short form (ICIQ-SF), Women Irritative Prostate Symptoms Score (W-IPSS), Patient Global Impression of Severity (PGI-S) and Patient Global Impression of Improvement (PGI-I) questionnaires were used. Objective and subjective outcomes were the primary outcome measures of the study. SPSS software was used for data analysis.

Results

206 patients who underwent the SIS procedure were reviewed. At 1 year follow-up there were 196 women available for the analysis: 69 were normal weight subjects, 91 overweight and 36 obese. Patients in all BMI groups reported a significant improvement in their condition. Nevertheless there was a trend towards lesser objective efficacy of SIS with increasing body weight, with a significant difference between obese women and normal subjects: 75% vs 91.3%, p = 0.049; OR 3.74 (95% CI 1.19–11.76). Analysis of the ICIQ-SF and PGI-I showed significant lower mean ± SD improvement in obese women when compared with their normal or overweight counterparts, together with a significantly lower number of obese patients reporting themselves as very much improved or much improved.

Conclusions

Single incision slings seem to be an effective treatment regardless of BMI, but obese women had nearly 4 times the odds of objective failure as compared to normal weight women.     

Offspring birth weight and maternal fasting lipids in women screened for gestational diabetes mellitus (GDM)

Objectives

Maternal lipid metabolism is altered during pregnancy but little is known about the influence of these alterations on either intrauterine fetal development or maternal wellbeing. The purpose of this study was to examine the relationship between both fasting cholesterol and triglycerides and offspring birth weight in women screened selectively for gestational diabetes mellitus (GDM).

Study design

In a prospective observational study in a University Maternity Hospital, women were recruited at their convenience when they were screened for GDM with a diagnostic 75 g oral glucose tolerance test (OGTT). An additional sample was taken for a lipid profile at the time the fasting glucose was obtained. Clinical and socio-demographic details were recorded.

Results

Of the 189 women recruited, the mean age was 32 years, 35.4% (n = 67) were primigravidas, 44.1% (n = 82) were obese and 11.6% (n = 22) had an abnormal OGTT. On univariate analysis, increasing birth weight was correlated positively with multiparity, first trimester body mass index (BMI), GDM and hypertriglyceridaemia but not with cholesterol levels. On multivariate analysis, increased birth weight correlated positively only with hypertriglyceridaemia.

Conclusions

This study provides further evidence that maternal hypertriglyceridaemia is important in programming intrauterine fetal growth and raises questions about whether women should be screened selectively for dyslipidaemia before, during and after pregnancy.     

The value of imaging of the lungs in the diagnostic workup of patients with endometrial cancer

Objective

Imaging of the lungs is part of the routine diagnostic workup of patients with endometrial cancer. The present study aimed to determine the incidence of lung metastases in patients with endometrial cancer and to evaluate the clinical relevance of preoperative chest imaging in this population.

Methods

A retrospective cross-sectional study was performed in four regional and one university hospital in the southeastern part of the Netherlands. A total of 784 patients with epithelial endometrial cancer diagnosed between 2002 and 2010 in five hospitals were included. Patients were followed up for at least 1 year.

Results

Of 784 patients, 541 (69.0%) underwent thoracic imaging and 11 showed findings suspicious for metastases perioperatively or during the 1-year follow-up period. In eight patients, the thoracic metastases were related to their endometrial cancer, resulting in an overall incidence of 1.0% (8/784, 95% CI = 0.3–1.7%). These eight patients had high-risk subtypes of endometrial cancer (serous, clear cell or poorly differentiated endometrioid), and the incidence was 4.1% (8/193, 95% CI = 1.9–8.3%) for these subtypes. Lung metastases were not detected in any of the patients with low-risk subtypes of endometrial cancer (n = 566) at the time of diagnosis (95% CI = 0–0.8%).

Conclusions

The probability of detecting thoracic metastases during the diagnostic workup of patients with endometrial cancer is low. The present data suggest that thoracic imaging could be omitted from the diagnostic workup of patients with low-risk endometrial cancer.     

Predictors of resolution of complex atypical hyperplasia or grade 1 endometrial adenocarcinoma in premenopausal women treated with progestin therapy

Objective

To identify clinical and pathologic predictors of response to progestin treatment in premenopausal women with complex atypical hyperplasia (CAH) and Grade 1 endometrial adenocarcinoma (Grade 1 EA).

Methods

Forty premenopausal patients with Grade 1 EA or CAH who underwent progestin therapy for a minimum of 8 weeks were retrospectively identified. Patient characteristics and histopathologic features of pretreatment and first follow-up endometrial specimens were evaluated as predictors of resolution, defined as absence of hyperplasia or carcinoma.

Results

Kaplan-Meier analysis indicated 63% resolution at 18 months of follow-up. Multivariate classification analysis showed that resolution rates were higher in individuals with a low pre-treatment qualitative abnormal architecture score and a BMI < 35 (Standardized Resolution Ratio (SRR) = 1.48, p = 0.03). The diagnosis of benign endometrium or simple hyperplasia on the first follow-up specimen was highly predictive of resolution (SRR = 2.25, p = 0.002). Resolution rates were lower among subjects with a high pre-treatment qualitative abnormal architecture score (SRR = 0.37, p < 0.03) and lowest in subjects whose first follow-up specimen showed persistent complexity, atypia, or carcinoma with adjacent stromal decidualization (SRR = 0.24, p = 0.002).

Conclusions

Clinical and pathologic parameters can predict response to progestin therapy in premenopausal women with CAH and Grade 1 EA. A low likelihood of resolution is predicted by an unfavorable pre-treatment architectural score and lack of pathological response in the first specimen, despite adjacent stromal decidualization.     

Combined use of preoperative transvaginal ultrasonography and intraoperative gross examination in the assessment of myometrial invasion in endometrial carcinoma

Objective

To evaluate the diagnostic performance of gross examination and transvaginal ultrasonography in the assessment of the depth of myometrial infiltration when they are used alone or together as a combined test.

Study design

The data of 219 consecutive patients with a diagnosis of endometrial cancer were evaluated retrospectively. Transvaginal ultrasound was carried out as a part of the routine preoperative work-up within three days of surgical intervention in all cases. All patients underwent hysterectomy with bilateral salpingo-oophorectomy and routine surgical staging and all uterine specimens were examined immediately after hysterectomy. The depth of myometrial invasion was classified into two groups: no or <50% invasion and ≥50% invasion. The findings of ultrasound and intraoperative gross examination were compared with the final histopathological results. The data of these two methods were integrated to evaluate the diagnostic performance of the combined test. If the results of myometrial invasion evaluation were different for the same patient, the deeper one (the depth of invasion ≥50%) was accepted.

Results

Sensitivity, specificity, PPV, NPV and accuracy of preoperative ultrasonography in predicting myometrial infiltration ≥50% were 62%, 81%, 60%, 82%, and 75% respectively. The corresponding rates for intraoperative gross examination were 61%, 88%, 70%, 83% and 79%, respectively. For the combined test they were 78%, 76%, 60%, 88% and 70% respectively. There was no statistically significant difference in sensitivity and specificity between ultrasound and gross examination. The sensitivity of the combined test was significantly higher than that of ultrasound and gross examination (p = 0.001 and p < 0.0001, respectively). The specificity of the combined test was significantly lower than that of TVS and gross examination (p = 0.008 and p < 0.0001, respectively).

Conclusion

Combining ultrasonography and intraoperative gross examination may be a good option to assess the depth of myometrial invasion, as it has a higher sensitivity and negative predictive value in comparison to using these methods alone.     

Abnormal uterine bleeding in peri-menopausal age: Diagnostic options and accuracy

Objectives

Various diagnostic techniques have been evolved over the periods to determine the etiology of abnormal uterine bleeding in peri-menopausal women, but their accuracy has not been compared properly. In this study diagnostic accuracy of trans-vaginal sonography (TVS), saline infusion sonography (SIS) and dilatation & curettage (D & C) were compared with hysteroscopic guided biopsy to determine the etiology.

Methods

In this study, 252 patients had to undergo trans-vaginal sonography and saline infusion sonography in the same sitting followed by hysteroscopic-guided biopsy and dilatation and curettage. All the materials were sent for histopathological examination.

Results

In determining uterine pathology, positive likelihood ratio (PLR) of TVS, SIS and D & C are 2.81, 7.5 and 3.81 respectively considering hysteroscopy as standard.

Conclusion

Sensitivity of SIS as a test for detecting pathology in abnormal uterine bleeding (AUB) is high and can be easily performed on out patient basis. D&C has a very low sensitivity and is unacceptable as a screening test for the same conditions.     

Abnormal cervical cytology among HIV-positive women in Nigeria

Objective

To determine the prevalence of abnormal cervical smears and high-grade lesions among HIV-positive and HIV-negative women, and to assess the relationship between severity of disease and CD4 count.

Methods

In a prospective cross-sectional comparative study, 250 HIV-positive and 250 HIV-negative women attending the University of Port Harcourt Teaching Hospital, Port Harcourt, Nigeria, were enrolled between January and March 2012. Cervical smear samples were collected from participants, examined, and reported via the Bethesda system. Data management and analysis was done with SPSS. Differences between the 2 study groups were determined by χ² test and Student t test.

Results

The prevalence of abnormal cervical smears was significantly higher among HIV-positive women (34.4%) than among HIV-negative women (20.2%) (P < 0.01). The proportion of high-grade lesions was significantly higher among HIV-positive women (23.5%) than among HIV-negative women (8.2%) (P = 0.025). HIV-positive women with a CD4 count below 500 cells/mm³ had significantly more abnormal cervical smears (28.3%) compared with those with a CD4 count of 500 cells/mm³ or more (6.1%) (P = 0.04).

Conclusion

HIV-positive women were found to be at significantly greater risk of developing abnormal cervical cytology and high-grade lesions compared with HIV-negative women.     

Nibrin is a marker of clinical outcome in patients with advanced serous ovarian cancer treated in the phase III OVA-301 trial

Objective

This study investigated the relationship between 13 proteins involved in DNA damage and the outcomes of patients with recurrent ovarian cancer (ROC).

Patients and methods

Immunohistochemistry staining was performed in 114 diagnostic samples from patients with serous ROC who participated in the OVA-301 study, which compared pegylated liposomal doxorubicin (PLD) with a combination of trabectedin plus PLD. Percentage of positive cells for every marker was calculated and correlated with overall response rate (ORR), progression-free survival (PFS) and overall survival (OS).

Results

A statistically significant correlation between high levels of nibrin and lower ORR (P = 0.03), shorter PFS (P = 0.007) and shorter OS (P = 0.01) was observed. After stratification, in patients with platinum-sensitive disease treated with the combination of trabectedin plus PLD, high levels of nibrin correlated with lower ORR (P = 0.01) and shorter PFS (P = 0.02). A better clinical outcome (ORR, PFS and OS) was also associated to low levels of CHK2 in trabectedin plus PLD treated patients. No correlations were found in PLD-treated patients. According to the results of a multivariate analysis, there was a statistically significant correlation between high nibrin (P = 0.001) and low BRCA2 levels (P = 0.03) and a worse PFS, and between high nibrin levels and a worse OS (P = 0.006).

Conclusion

Our results indicate that high nibrin expression seems to be associated with a worse clinical outcome in serous ROC, particularly in patients treated with the combination trabectedin plus PLD. Prospective studies to determine clinical usefulness of nibrin as a possible biomarker in other series of patients with ROC are warranted.     

Diagnostic accuracy of colposcopy in relation to human papillomavirus genotypes and multiple infection

Objective

The aim of this study is to evaluate the diagnostic accuracy of colposcopy for cervical intraepithelial neoplasia grade 3 or worse (CIN3 +) in relation to the detection of human papillomavirus (HPV) type 16 and multiple HPV infection.

Methods

A cohort study of 2526 subjects attending a colposcopic service because of cytological abnormalities. HPV genotypes were identified using the INNO–LIPA genotyping system.

Results

The final colposcopic/pathological diagnoses were as follows: 1282 (50.8%) negative, 709 (28.1%) CIN1, 169 (6.7%) CIN2, 318 (12.6%) CIN3 and 48 (1.9%) invasive cervical cancer, respectively. Among women with ASCUS/LSIL, assuming any colposcopic abnormality as a cut-off, there were no significant differences in the sensitivities (83.8%, 95% CI = 76–89.6 as compared to 84.1%, 95% CI = 73.2–91.1, p = 0.9) and ROC curves (0.61, 95% CI = 0.58–0.65 as compared to 0.59, 95% CI = 0.54–0.64, p = 0.5) in the detection of CIN3 + lesions between subjects with single and multiple high-risk infection, and between subjects infected by HPV16 (83.1%, 95% CI = 73.7–89.7, ROC = 0.59, 95% CI = 0.54–063) or other high-risk HPVs (84.7%, 95% CI = 75.6–90.8, ROC = 0.62, 95% CI = 0.58–0.66, p = 0.8 and p = 0.6 compared to HPV16). After correction for confounders, the odds ratios of CIN3 + associated with any abnormal colposcopic findings were 2.47 (95%CI = 1.44–4.23, p = 0.001) among HPV16 positive, 3.34 (95% CI = 2.16–5.42, p < 0.001) among other high-risk HPVs and 1.3 (95% CI = 0.72–2.48, p = 0.36) among subjects with negative/low-risk HPVs.

Conclusion

In routine clinical practice, multiple infection or HPV16 positivity did not affect colposcopic accuracy in the diagnosis of CIN3 + lesions. The sensitivity of colposcopy was poor among subjects who were uninfected or infected by low-risk HPV genotypes.