Evaluation of patients with advanced epithelial ovarian cancer before primary treatment: correlation between tumour burden assessed by [18F]FDG PET/CT volumetric parameters and tumour markers HE4 and CA125.

OBJECTIVES: Accurate assessment of disease extent is required to select the best primary treatment for advanced epithelial ovarian cancer patients. Estimation of tumour burden is challenging and it is usually performed by means of a surgical procedure. Imaging techniques and tumour markers can help to estimate tumour burden non-invasively. 2-[18F]FDG PET/CT allows the evaluation of the whole-body disease. This study aimed to correlate HE4 and CA125 serum concentrations with tumour burden evaluated by volumetric 2-[18F]FDG PET/CT parameters in advanced high-grade epithelial ovarian cancer. METHODS: We included 66 patients who underwent 2-[18F]FDG PET/CT and serum tumour markers determination before primary treatment. Volumes of interest were delimited in every pathological uptake. Whole-body metabolic tumour volume (wb_MTV) and total lesion glycolysis (wb_TLG) were calculated summing up every VOI's MTV value. SUVmax thresholds were set at 40% (MTV40 and TLG40) and 50% (MTV50 and TLG50). In addition, four VOI subgroups were defined: peritoneal carcinomatosis, retroperitoneal nodes, supradiaphragmatic nodes, and distant metastases. MTV and TLG were calculated for each group by adding up the corresponding MTV values. TLG was calculated likewise. RESULTS: wb_MTV and wb_TLG were found to be significantly correlated with serum CA125 and HE4 concentrations. The strongest correlation was observed between HE4 and wb_MTV40 (r = 0.62, p < 0.001). Pearson's correlation coefficients between peritoneal carcinomatosis MTV40 and tumour markers were 0.61 (p < 0.0001) and 0.29 (p = 0.02) for HE4 and CA125 respectively. None of these tumour markers showed a positive correlation with tumour load outside the abdominal cavity assessed by volumetric parameters. CONCLUSION: HE4 performs better than CA125 to predict metabolic tumour burden in high-grade epithelial ovarian cancer before primary treatment. 2-[18F]FDG PET/CT volumetric parameters arise as feasible tools for the objective assessment of tumour load and its anatomical distribution. These results support the usefulness of HE4 and PET/CT to improve the stratification of these patients in clinical practice. KEY POINTS: • In patients with high-grade advanced ovarian epithelial carcinoma, both CA125 and HE4 correlate to whole-body tumour burden assessed by PET/CT before primary treatment. • HE4 estimates peritoneal disease much better than CA125. • PET/CT volumetric parameters arise as feasible tools for the objective assessment of tumour load and its anatomical distribution.

Candidate HPV genotypes not included in the 9-valent vaccine for prevention of CIN 2-3.

OBJECTIVES: To identify the prevalence of human papillomavirus genotypes - as a single infection or co-infection - not included in the 9-valent (9v) HPV vaccine among women with cervical intraepithelial neoplasia (CIN 2-3). METHODS: Retrospective study of 1700 women referred due to abnormal cytology to Sant Joan de Deu Hospital. We selected 849 patients with CIN 2 or CIN 3 diagnosis confirmed by biopsy. An HPV test, a second cytology, and colposcopy were performed on all patients.Those with abnormal colposcopy underwent cervical biopsy. Patients with abnormal cytology and normal colposcopy or transformation zone type 3 underwent endocervical curetage. Conization was performed if punch biopsy or endocervical curetage confirmed CIN 2-3 or if a CIN 1 lesion persisted (diagnosed by biopsy) over 2 years in patients over 25 years of age. Comparisons for qualitative variables were analyzed with the chi-squared test. Analysis of variance was used for comparisons involving more than two samples. RESULTS: HPV was detected in 746 of 849 patients (87.9%) and in 306 (41%) of those where more than one HPV genotype was present. The more frequent genotypes detected as single infection were: HPV-16 (267/849%-31.4%), HPV 31 (34/849-4%), HPV-33 (20/849%-2.4%), HPV-58 (17/849%-2%), HPV-51 (15/849%-1.8%), and HPV-53 (12/849%-1.4%). The more frequent genotypes isolated including multiple HPV infection were HPV-16 (427/849%-50.2%), HPV-31 (108/849%-12.7%), HPV-51 (79/849%-9.3%), HPV-33 (67/849%-7.8%), HPV-58 (67/849%-7.8%), and HPV-52 (59/849%-6.9%). In total, 78% of women diagnosed with CIN 2 or CIN 3 had an infection by a HPV genotype included in the 9v vaccine. Of the 849 women diagnosed with CIN 2 or CIN 3, 103 (12.1%) tested negative for HPV and 106 (12.4%) tested positive for low-risk HPV types. CONCLUSIONS: Inclusion of HPV-51, 53, 66, and 35 in a new vaccine may not be advisable as most are detected as coinfection with other high-risk genotypes that are already included in the current vaccines.

Long-term oncological outcomes of patients with negative sentinel lymph node in vulvar cancer. Comparative study with conventional lymphadenectomy.

INTRODUCTION: The aim of this study was to compare oncological outcomes and morbidity in patients with early-stage vulvar cancer with negative sentinel lymph node (SLN) biopsy vs negative inguinofemoral lymphadenectomy (IFL). MATERIAL AND METHODS: Study with retrospectively collected data in patients with squamous cell vulvar carcinomas ≤ 4 cm without suspected inguinofemoral lymph node metastases. Only patients with negative nodes after histopathology procedure were followed. Patients who underwent only SLN were compared with patients who underwent IFL ± SLN to compare recurrences, survival rates and morbidity. RESULTS: Ninety-three patients were eligible for follow up: 42 with negative SLN and 51 with negative IFL ± SLN. The median follow-up period was 60.4 months (range 6.7-160.7). The rate of isolated first groin recurrence was 4.8% in patients with negative SLN and 2.0% in patients with negative IFL ± SLN (P = 0.587) and the rates of first isolated local recurrence were 28.6% and 31.4%, respectively (P = 0.823). Only 1 patient (2.4%) in the group of negative SLN had distant recurrence. The disease-specific survival rate at 5 years was 83.3% in the negative SLN group and 92.2% in the negative IFL ± SLN group (P = 0.214). We observed a higher rate of wound breakdown and infection after IFL than SLN biopsy (17.6% vs 10.6%; P = 0.020) and lymphedema (33.3% vs 0%; P < 0.001). CONCLUSIONS: We report in the same population of patients with early-stage vulvar cancer that SLN biopsy does not have significantly higher rates of groin recurrences or lower survival rates compared with IFL. Moreover, the SLN procedure has less morbidity, which should encourage gynecologists to abandon IFL.

Primary Low-Grade Peritoneal Serous Carcinoma in a Woman With Psammoma Bodies on Cervicovaginal Cytology.

Psammoma bodies in cervicovaginal cytology are a rare finding associated with malignant tumours. A 62-year-old woman was referred to our centre for cytology with nuclear atypia and psammomatous bodies suspicious of malignancy. A complete gynaecological examination was performed including colposcopy and ultrasound without significant changes. Hysteroscopy was performed to detect endometrial or endocervical malignancy, endometrial biopsy showed psammoma bodies and atrophic endometrium. Endocervical and cervical biopsies were negative for malignancy. Cervicovaginal cytology and human papillomavirus (HPV) testing were repeated. The result was suggestive of adenocarcinoma and negative for HPV. Laparoscopic hysterectomy with bilateral salpingo-oophorectomy was indicated due to two cervicovaginal cytologies with suspicion of malignancy. Low-grade peritoneal serous carcinoma was diagnosed on the surface of the uterus, ovaries and peritoneum. A second laparoscopy was performed to exclude other pelvic or abdominal lesions, and disease was found in the peritoneum of the pelvis, abdomen and omentum. Adjuvant treatment with six cycles of carboplatin and paclitaxel was indicated. Psammoma bodies in cervicovaginal cytology are a rare clinical situation, and it is mandatory to exclude malignancy.

Pessary for Management of Cervical Varices Complicating Pregnancy.

BACKGROUND: Cervical varices complicating pregnancy are rare but can cause significant maternal and perinatal morbidity. There is limited evidence regarding the optimal management of bleeding caused by cervical varices during pregnancy. CASE: A 38-year-old woman was admitted to the hospital at 16 weeks of gestation due to vaginal hemorrhage in the setting of cervical varices accompanied by placenta previa. A cervical pessary was placed at 21 weeks of gestation without further bleeding. Magnetic resonance imaging demonstrated variceal reduction after pessary placement, and a cesarean delivery was performed at 36 weeks of gestation without complications. CONCLUSION: Cervical pessary should be considered as conservative option to control the bleeding associated with cervical varices during pregnancy.

[Ovarian vein thrombosis. Risk factors, diagnosis and treatment]. / Trombosis de la vena ovárica. Factores de riesgo, diagnóstico y tratamiento.

Ovarian vein thrombosis is an uncommon complication (0.002-0.05%) related to hypercoagulated status of women. The most frequent condition associated to ovarian vein thrombosis is pregnancy, but there are other possible causes. We present a case of a 31 year old pregnant woman at 16th week of gestation who had spontaneuos septic abortion complicated with an ovarian vein thrombosis. A discussion of risk factors, diagnostic and treatment options of ovarian vein thrombosis are presented.

Identification of vaccine human papillomavirus genotypes in squamous intraepithelial lesions (CIN2-3).

OBJECTIVE: To identify the prevalence of human papillomavirus vaccine genotypes and non-vaccine genotypes implicated in the appearance of cervical intraepithelial neoplasia (CIN2-3). METHODS: Prospective study of 519 women with abnormal cytology. All the women underwent a second Papanicolaou test, cervicovaginal sampling for type-specific HPV detection and colposcopy, and women with abnormal colposcopy results were referred to biopsy. Pearson's chi-square test was used for statistical analysis. RESULTS: HPV was detected in 340 patients (65.5%), and in 125 (24%) more than one HPV genotype was present. We selected 206 patients with CIN2 or CIN3 confirmed by biopsy. In 88 (42.7%) of these patients, HPV types 16 and 18 were detected, but only 58 (28.2%) without co-infection by other high-risk or probable high-risk HPV types. In 115 (55.8%) women diagnosed with CIN2 or CIN3 high-risk or probable high-risk HPV types other than 16 or 18 were found. High-risk and/or probable high-risk HPV genotypes not included in the vaccine were isolated in this study more frequently than 16 or 18, and this difference was statistically significant (p=0.047). Of the 206 women diagnosed with CIN2 or CIN3, 19 tested negative for HPV and 14 tested positive for low-risk HPV types. CONCLUSION: Only 28.2% of women with CIN2 or CIN3 confirmed by biopsy were infected exclusively by HPV type 16 or 18, a finding that places in doubt the degree of protection afforded by HPV vaccination.

[Elevated Ca 19.9 tumor marker without evidence of malignancy]. / Marcador tumoral Ca 19.9 aumentado sin evidencia de malignidad.

Tumor markers are a useful tool for surveillance of oncologic patients, whereas their role in the diagnosis of a malignancy is controversial. We present the case of a woman with a benign ovarian cyst with an unexpected elevation of Ca 19.9 after laparoscopic bilateral anexectomy.

Negative HPV testing among patients with biopsy-proven cervical intraepithelial neoplasia grade 2/3 or cervical cancer.

OBJECTIVE: To determine the proportion of patients diagnosed with cervical cancer or cervical intraepithelial neoplasia grade 2 or 3 (CIN 2/3) despite testing negative for HPV. METHODS: A prospective study was conducted at a university hospital in Barcelona, Spain, between March 2003 and January 2015 among women with abnormal cytology results according to the Bethesda classification system. All participants underwent HPV testing, cytology, and colposcopy. RESULTS: Among 1376 participants, 609 (44.3%) were diagnosed with CIN 2/3. Of these women, 74 (12.2%) tested negative for HPV. Among 479 women with colposcopy-guided biopsy sampling showing CIN 2/3, cone biopsy results that were negative for CIN 2/3 were more frequent among patients with negative HPV testing (13/61 [21.3%]) than among those with positive HPV tests (58/418 [13.9%]; P=0.03). Additionally, among 59 patients diagnosed with cervical cancer, 9 (15.3%) tested negative for HPV. CONCLUSION: The HPV test was negative for 12% and 15% of patients diagnosed with biopsy-proven CIN 2/3 and cervical cancer, respectively.

Obstetric and perinatal outcomes in women ≥40years of age: Associations with fetal growth disorders.

BACKGROUND: Evidence indicates that advanced maternal age is associated with adverse obstetric and perinatal outcomes. The purpose of this study was to evaluate pregnancy outcomes in women of advanced maternal age (≥40years). METHODS: Using a prospective study design, data were collected by the Department of Obstetrics at the San Joan de Deu Hospital of Barcelona during the 1 June 2009 to 31 May 2012 period. The results were compared across three maternal age groups (≥40 [n=654], 35-39 [n=2781], and <35 [n=7893] years). RESULTS: Of the 11328 births recorded during the study period, pregnancy-related complications were more common in women ≥40years of age. The most common disorder was diabetes (8.5% in the ≥40, 5.3% in the 35-39, and 3.0% in the <35years age groups). The women ≥40years of age also had significantly more premature births (p=0.001) and cesarean sections (17% in the ≥40, 12.5% in the 35-39, and 7.9% in the <35-year age groups; p=0.001). Intrauterine growth retardation was significantly more frequent in women aged ≥40years (17.4% in the ≥40, 15% in the 35-39, and 14.0% in the <35-year age groups; p=0.03). Fetal macrosomia was significantly more common in women ≥40years (15.4% in the ≥40, 12.6% in the 35-39, and 12% in the <35-year age groups; p=0.03). CONCLUSION: Maternal age ≥40years was associated with poorer obstetric and perinatal outcomes and increased the risks of cesarean section, intrauterine growth retardation, and fetal macrosomia.

Hormonal environment in the induction of breast cancer in castrated rats using dimethylbenzanthracene: influence of the presence or absence of ovarian activity and of treatment with estradiol, tibolone, and raloxifene.

OBJECTIVE: The influence of hormone therapy on the induction or the promotion of breast cancer has yet to be determined. Recent studies establish a cause-effect relation between hormones and cancer, although epidemiological data and studies of tumor behavior give rise to doubts. The aim of the study was to observe and evaluate the influence of different hormonal environments on the induction of breast cancer in a well-established experimental model. DESIGN: In this experimental animal study, breast cancer was induced by using a single intragastric dose of 20 mg of dimethylbenzanthracene in prepubertal Sprague-Dawley rats randomized into five groups: group 1 (control); group 2 (castrated prepubertal animals); and groups 3, 4, and 5 (castration of prepubertal animals followed by hormonal treatment starting at puberty [11 weeks] with tibolone, raloxifene, and estradiol, respectively). Follicle-stimulating hormone and estradiol levels were measured at 6, 11, 16, and 31 weeks. RESULTS: Absence of ovarian activity was observed in groups 2, 3, 4, and 5, as well as the expected variations in hormone levels in all groups. Breast cancers were obtained in 100% of the animals in the control group, with an average of four (two to seven) tumors per animal in this group. Only one cancer appeared in groups 2, 3, and 4, and none appeared in group 5. CONCLUSIONS: In this experimental model and using the hormone treatments chosen, neither the treatments nor the absence of ovarian activity induced breast cancer.

Detection of human papillomavirus infection in women attending a colposcopy clinic.

BACKGROUND: Infection by human papillomavirus (HPV) is the main cause of and a necessary factor for cervical cancer. There are more than 100 known HPV genotypes, although HPV genotypes do not all have the same risk of inducing cervical cancer. The main aim of this study is to know the distribution of different types of HPV in women attending a colposcopy clinic for cervical dysplasia. METHODS: We prospectively identified and enrolled a cohort of women followed for cervical dysplasia who were referred to the colposcopy clinic of University Hospital Sant Joan de Déu in Barcelona, Spain, from April 2003 to April 2007. Two cervical scrape samples from each patient were collected for routine cytology and for identification of HPV DNA. During the study period, 2 techniques (Line Probe assay and microarray assay) were used consecutively. FINDINGS: HPV DNA was detected in 68% of patients (338 of 496 women) with statistically significant differences in positive results according to the cytologic category. Overall, the type distribution showed a predominance of genotype HPV-16 (27% of the total patients) followed by HPV-53 (9.4%), HPV-51 (8%), and HPV-51 (8%). Multiple genotype detection was observed in 35.5% of the patients with HPV infection. HPV-16 was mainly associated with the probable high-risk genotypes: HPV-53 and HPV-66. CONCLUSION: The higher prevalence of high-risk nonvaccine genotypes should be considered to increase vaccine efficiency.

Value of endocervical ureaplasma species colonization as a marker of preterm delivery.

AIMS: To study the predictive value for preterm delivery of colonization of the cervix and vagina by ureaplasmas and other potentially pathogenic microorganisms. METHODS: Prospective analysis of a study group of 200 pregnant women with preterm labor and intact membranes, and a control group of 50 pregnant women. The subjects in both groups were between 24 and 34 weeks of gestation. Ureaplasma spp. and Mycoplasma hominis endocervical cultures were performed for both groups. RESULTS: In the study group, 70 of the women delivered preterm, and all women in the control group carried their pregnancies to full term. Cervical cultures for Ureaplasma spp. were positive in 119 women, and were isolated more frequently in the study group (51.5%) than in the control group (32%), and more frequently in subjects in the study group who delivered preterm (65%) than in those who had a full-term delivery (45%), differences that were statistically significant. CONCLUSION: Detection of Ureaplasma spp. in the endocervix has a statistically significant relationship to preterm labor (p = 0.03) and preterm delivery (p = 0.02) in pregnant women with preterm labor and intact membranes.

The value of interleukin-8, interleukin-6 and interleukin-1beta in vaginal wash as predictors of preterm delivery.

AIMS: To study the value of interleukin (IL)-8, IL-6 and IL-1beta in vaginal wash as predictors of preterm delivery. METHODS: A prospective analysis of a study group of 200 pregnant women between 24 and 34 weeks of gestation with intact membranes and preterm labor and a control group of 50 pregnant women during the same period of gestation. The controls had uncomplicated pregnancies and subsequently delivered at term. Samples of vaginal secretions were collected from both groups and analyzed for IL-1beta, IL-6 and IL-8 concentrations. RESULTS: Of the women in the study group, 70 had preterm deliveries, while all women in the control group had full-term deliveries. Compared with the control group, the study group had significantly higher concentrations (p < 0.021) of IL-1beta, IL-6 and IL-8. The women in the study group delivering preterm also had IL-1beta, IL-6 and IL-8 concentrations significantly greater (p < 0.001) than those of the same group delivering full term. ROC curves were used to establish cut-off points for the three interleukins to predict preterm delivery. We did not find a cut-off point with an appropriate sensitivity and specificity. CONCLUSION: The concentrations of interleukins in vaginal wash were significantly higher both in the women with preterm labor and in those delivering preterm. While values differed between controls and those with the preterm labor, no cut-off can be obtained to use the results of IL-1beta, IL-6 and IL-8 as a predictor clinically.

Trombosis de la vena ovárica: Factores de riesgo, diagnóstico y tratamiento / Ovarian vein thrombosis: risk factors, diagnosis and treatment

La trombosis de la vena ovárica es una complicación muy poco frecuente (0.002-0.05%), que se observa en mujeres que presentan un incremento en los factores de coagulación. La principal situación en la que es posible detectar esta complicación es el embarazo, aunque no es la única. Se describe el caso de una mujer de 31 años de edad, gestante de 16 semanas, que presenta un aborto espontáneo séptico complicado con una trombosis de la vena ovárica. Se aprovecha el caso clínico para revisar en la literatura los factores de riesgo, el diagnóstico y el tratamiento de esta inusual patología.

Ovarian vein thrombosis is an uncommon complication (0.002-0.05%) related to hypercoagulated status of women. The most frequent condition associated to ovarian vein thrombosis is pregnancy, but there are other possible causes. We present a case of a 31 year old pregnant woman at 16th week of gestation who had spontaneuos septic abortion complicated with an ovarian vein thrombosis. A discussion of risk factors, diagnostic and treatment options of ovarian vein thrombosis are presented.

Marcador tumoral ca 19.9 aumentado sin evidencia de malignidad / Elevated Ca 19.9 tumor marker without evidence of malignancy

Los marcadores tumorales son de gran utilidad clínica en el seguimiento de los pacientes oncológicos. Su papel en el diagnóstico de tumoraciones malignas es controvertido. Presentamos un caso de una mujer con un quiste ovárico benigno en la cual los marcadores aumentan de forma inexplicable después de la extirpación del mismo.

Tumor markers are a useful tool for surveillance of oncologic patients, whereas their role in the diagnosis of a malignancy is controversial. We present the case of a woman with a benign ovarian cyst with an unexpected elevation of Ca 19.9 after laparoscopic bilateral anexectomy.