Can MRI help assess aggressiveness of endometrial cancer?

AIM: To identify potential magnetic resonance imaging (MRI) biomarkers to predict the aggressiveness of endometrial cancer. MATERIALS AND METHODS: Seventy-one patients with endometrial cancer who underwent MRI staging were analysed retrospectively. The signal intensity (SI) of the tumours was assessed on sagittal T2-weighted imaging (WI) and sagittal T1WI sequences). The depth of myometrial invasion, tumour grade and subtype, lymphovascular invasion, and microsatellite stability status were assessed histopathologically, and these findings were compared with MRI findings using logistic regression. The log-rank test was used to assess differences in survival among groups defined by different MRI measurements. RESULTS: Tumours with qualitative higher signal than that of normal myometrium on the late T1WI DCE image sequences were more likely to have lymphovascular space invasion (p<0.001). Tumours that had a higher SI tumour ratio (T1 post-contrast arterial/T1 precontrast) had a higher chance of being microsatellite stable (odds ratio 2.36). The SI ratio of the tumour to the myometrium showed that lower T2 tumour/T2 myometrial ratio correlated with ≥50% depth of myometrial invasion as determined by imaging (p=0.006). Endometrial tumours showing a SI of >209 on delayed T1WI sequences had longer recurrence-free survival than those with tumours showing a SI ≤209 (p=0.014). Tumour subtype and grade were not associated with MRI findings. CONCLUSION: The SI of endometrial cancer on MRI may be used to predict the aggressiveness of the tumour and microsatellite stability status. Further studies are needed to confirm these findings.

Combination therapy with topotecan, paclitaxel, and bevacizumab improves progression-free survival in recurrent small cell neuroendocrine carcinoma of the cervix.

OBJECTIVES: To assess if the combination of topotecan, paclitaxel, and bevacizumab (TPB) was active in recurrent SCCC and to compare the survival of patients with SCCC who received TPB to a group of women with SCCC who did not receive this regimen. METHODS: We retrospectively analyzed women with recurrent SCCC who received chemotherapy as primary therapy. Women treated with TPB for first recurrence were compared to women treated with non-TPB chemotherapy. RESULTS: Thirteen patients received TPB, and 21 received non-TPB chemotherapy, most commonly platinum with or without a taxane. Median progression-free survival (PFS) was 7.8months for TPB and 4.0months for non-TPB regimens (hazard ratio [HR] 0.21, 95% CI 0.09-0.54, P=0.001). Median overall survival (OS) was 9.7months for TPB and 9.4months for non-TPB regimens (HR 0.53, 95% CI 0.23-1.22, P=0.13). Eight women (62%) who received TPB versus four (19%) who received non-TPB regimens were on treatment for >6months (P=0.02), and four patients (31%) in the TPB group versus two (10%) in the non-TPB group were on treatment for >12months (P=0.17). In the TPB group, three patients (23%) had complete response, two (15%) had complete response outside the brain with progression in the brain, 3 (23%) had a partial response, 2 (15%) had stable disease, and 3 (23%) had progressive disease. CONCLUSIONS: These findings indicate that TPB for recurrent SCCC significantly improved PFS over non-TPB regimens, and trends towards improved OS. Furthermore, a significant number of patients had a durable clinical benefit.

Quality of life after radical trachelectomy for early-stage cervical cancer: A 5-year prospective evaluation.

OBJECTIVES: To longitudinally assess quality of life (QOL) in women undergoing radical trachelectomy for early-stage cervical cancer. METHODS: We prospectively enrolled patients with stage IA1-IB1 cervical cancer prior to undergoing radical trachelectomy to complete validated QOL instruments. These instruments included the General Health-Related QOL (SF-12), Functional Assessment of Cancer Therapy-Cervix (FACT-Cx), MD Anderson Symptom Inventory (MDASI), Female Sexual Functioning Index (FSFI), and Satisfaction with Decision scale (SWD). Instruments were filled out at baseline, postoperatively at 6weeks, 6months, 1year, and annually thereafter for 4years. RESULTS: Thirty-nine patients enrolled in the study, and 32 patients were evaluable. The scores for FSFI-arousal (p=0.0002), lubrication (p<0.0001), orgasm (p=0.006), pain (p=0.01), satisfaction (p=0.03) and total score (p=0.004) showed a significant decline at 6weeks then returned to baseline levels by 6 months. The scores for FACT-Cx functional well-being (p=0.02) and physical well-being (p<0.0001), SF-12 bodily pain (p<0.0001), physical functioning (p<0.0001), role physical (p<0.0001), role emotional (p=0.03), social functioning (p=0.002), and MDASI total (p=0.04) showed significantly worsened symptoms at 6weeks then returned to baseline by 6months. The scores for FACT-Cx emotional well-being showed significant worsening of symptoms that persisted at 6-weeks (p=0.004), 6months (p=0.007), 1year (p=0.001), 2years (p=0.002), and 4 years (p=0.03). There was no difference in SWD. CONCLUSIONS: Several quality of life assessments decline immediately postoperatively after radical trachelectomy, however, return to baseline thereafter. The long-term emotional impact of this surgery highlights a need for perioperative counseling in these patients.

Is MRI helpful in assessing the distance of the tumour from the internal os in patients with cervical cancer below FIGO Stage IB2?

AIM: To determine the ability of magnetic resonance imaging (MRI) in detecting tumour-free margins from the internal os (IO). MATERIALS AND METHODS: A database search yielded 79 women with early-stage cervical cancer who underwent radical hysterectomy and preoperative MRI. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of MRI in assessment of ≤5 and >5 mm IO involvement were calculated with histopathological surgical specimen findings considered to be the reference standard. A main and subset analysis was performed. The subset analysis included only those patients who would have been considered for radical trachelectomy. RESULTS: For predicting a distance between the tumour and the IO of ≤5 mm, MRI had a sensitivity of 73%, a specificity of 98.3%, a PPV of 95%, a NPV of 88.1%, and an accuracy of 89.8% for the main analysis, and sensitivity of 81.8%, a specificity of 93.2% a PPV of 69.2% a NPV of 96.5% and an accuracy of 91.4% for the subset analysis. CONCLUSION: MRI has high specificity, NPV, and accuracy in detecting tumour from the IO, making MRI suitable for treatment planning in patients desiring trachelectomy to preserve fertility.

Vulvar intraepithelial neoplasia (VIN 2/3): comparing clinical outcomes and evaluating risk factors for recurrence.

OBJECTIVE: To evaluate demographic and clinical characteristics associated with the development of vulvar intraepithelial neoplasia (VIN 2/3), and factors associated with recurrence. METHODS: A retrospective chart review of 303 patients with VIN 2/3 evaluated at a single institution between 1993 and 2011 was performed. Medical records were reviewed for demographic information, risk factors, treatment type, pathologic diagnosis, and recurrence/outcome information. RESULTS: Median age at diagnosis was 47 years (range 14-87). 40% of patients reported current tobacco use and 26% reported previous use. Primary treatment included excision (n=176, 59%), laser ablation (n=40, 13%), imiquimod (n=22, 7.4%), excision with laser (n=24, 8.1%), excision with imiquimod (n=10, 3.4%), and laser with imiquimod (n=3, 1.0%). 92 patients (62.6%) were noted to have positive margins, which was associated with larger tumor size (p=0.004). 87 patients (28.7%) developed recurrent disease, which was associated with smoking (p<0.001), larger lesion size (p=0.016), and positive margins (p=0.005). On univariate analysis, higher rates of recurrence were associated with laser ablation (45.0%) compared with excision (26%) or imiquimod (13.6%) (p=0.018). However, on multivariate analysis of recurrence-free survival (RFS) these therapies were equivalent when used individually, but the use of excision plus laser had an adverse impact on RFS (p<0.001). 7 patients (2.3%) recurred with invasive disease a median of 109 months (range 12-327) from initial VIN 2/3 diagnosis. CONCLUSIONS: This large cohort of women with VIN 2/3 further delineates the demographic and clinical factors associated with VIN 2/3. High rates of recurrence were noted and found to be associated with smoking, larger lesion size, and positive margins. While higher rates of recurrence were found among those treated with laser ablation, it was not inferior with respect to RFS when used alone, but the use of laser with excision was associated with decreased RFS. Our findings provide hypothesis-generating material for further research in the management of VIN2/3.

Modified uterine manipulator and vaginal rings for total laparoscopic radical hysterectomy.

At present, there is no standard technique that allows surgeons performing total laparoscopic radical hysterectomy to complete the colpotomy and remove an adequate (2-cm) margin of upper vaginal tissue while maintaining adequate pneumoperitoneum. We evaluated the feasibility and safety of using a modified uterine manipulator for total laparoscopic radical hysterectomy in patients with cervical or endometrial cancer. A retrospective review was performed in all patients who underwent total laparoscopic radical hysterectomy using a modified uterine manipulator at our institution during the period April 2004 to December 2006. This analysis included 30 patients who underwent surgery with the modified uterine manipulator. There were no reports of difficulty with placement of the instrument, multiple attempts at placement, difficulty with uterine manipulation, or uterine perforation. In no patient was a vaginal incision or episiotomy required to fit the instrument through the introitus. In no case was there loss of pneumoperitoneum during colpotomy. Additional upper vaginal tissue had to be removed after intraoperative assessment of the adequacy of the surgical specimen in five (16.7%) of 30 patients. Use of the modified uterine manipulator according to our technique is safe and feasible, allowing for adequate vaginal resection and maintenance of pneumoperitoneum.

Laparoscopic port-site metastases in patients with gynecological malignancies.

OBJECTIVE: The purpose of this study is to review all reported cases of laparoscopic port-site metastases in patients with gynecological malignancies. Potential etiologies as well as options for prevention are discussed. METHODS: We searched the Medline database for English-language articles presenting raw data on laparoscopic port-site metastases in patients with gynecological malignancies. RESULTS: We found 31 articles describing port-site metastases in 58 patients. Forty patients had low malignant potential (seven patients) or invasive ovarian carcinoma (33 patients). The median age of these patients was 50 years (range: 22-79), and 83% had advanced (stage III or IV) disease. Seventy-one percent of the patients (24 of 34) had ascites, and 97% (29 of 30) had carcinomatosis. Seventy-five percent of the laparoscopic procedures in this group were performed for diagnosis. Median time to diagnosis of port-site metastases was 17 days (range: 4-730). Seventy-one percent of port-site recurrences (15 of 21) were isolated to a tissue-manipulating port. Twelve patients had port-site metastases after laparoscopy for cervical cancer. The median age was 44 years (range: 31-74). Eighty percent of cases were squamous cell carcinoma. In 75% of the patients, laparoscopy was performed for therapeutic purposes. The median time to diagnosis of port-site metastases was 5 months (range: 1.5-19). Four patients had port-site metastases after laparoscopy for uterine cancer. The median age was 63 years (range: 56-72). The median time to diagnosis of metastases was 13.5 months (range: 6-21). Half of the recurrences were in the tissue-manipulating port. Port-site metastases after laparoscopy were reported for one patient each with a diagnosis of fallopian tube carcinoma and vaginal carcinoma. CONCLUSIONS: Laparoscopic port-site metastases are a potential complication of laparoscopy in patients with gynecological malignancies, even in patients with early-stage disease.

Recruitment and screening policies and procedures used to establish a paid donor oocyte registry.

We have reviewed the demographic characteristics of, and report abnormalities noted in, the de-novo growth and development of a paid oocyte donation programme. The personal profiles of all prospective oocyte donors were reviewed. Acceptance or rejection of candidates was based upon screening the results of medical, genetic and psychological testing. A total of 603 candidates initially responded to our advertisement. From this pool, 313 individuals were considered suitable and contacted by telephone. Following further conversation, 176 women were scheduled an entry interview. On completion of the formal screening process, 17.6% (n = 31) of those actually interviewed were denied entry. Thus, from the initial interested parties, only 23% of women wishing to participate in oocyte donation were considered suitable candidates. Given the high attrition rate, we concluded that the need for rigorous and thorough medical, psychological and genetic testing is mandatory for the establishment of a donor registry. Furthermore, professional counselling of prospective donors with respect to the results of tests and the implications of test results with respect to their future medical and reproductive health, are important parts of providing comprehensive care.

Calcium influx following onset of electrical afterdischarge is not required for hormone secretion from neuroendocrine cells of Aplysia.

The neuroendocrine bag cells are an attractive model system for investigating cellular mechanisms mediating the effects of membrane excitability on hormone secretion because of the ability to easily monitor their electrical and secretory functions simultaneously. We investigated the role of extracellular calcium in regulating prolonged release of egg-laying hormone from bag cells following stimulation of an electrical afterdischarge. We report that calcium influx is required for initiation of the afterdischarge, but is not required for prolonged hormone secretion once the afterdischarge has been triggered.

The beta-core fragment of chorionic gonadotropin is not complexed to macromolecules in amniotic fluid.

A prior report claimed that amniotic fluid contains substantial quantities of beta-core fragment, a major degradation product of CG metabolism, complexed to macromolecules. In an attempt to confirm this finding, we measured beta-core fragment concentrations in 36 second- and 22 third-trimester amniotic fluid samples in a direct beta-core fragment RIA as well as a total CG RIA and found that all of the apparent immunoreactivity could be accounted for by the cross-reaction of CG and CG beta in the beta-core fragment RIA. Chromatography of concentrated pools of amniotic fluid or pregnancy serum failed to reveal a peak of CG immunoreactivity in the beta-core fragment elution area. However, chromatography after incubation of amniotic fluid or pregnancy serum with 3 mol/L ammonium thiocyanate resulted in a peak of apparent CG immunoreactivity in the area coinciding with the elution of ammonium thiocyanate and not purified beta-core fragment. The addition of ammonium thiocyanate to the CG RIA tubes resulted in apparent, but spurious, CG immunoreactivity. We conclude that amniotic fluid does not contain appreciable amounts of free or complexed beta-core fragment. We also were unable to confirm the presence of beta-core fragment complexed to macromolecules in pregnancy serum. Our results suggest that the previous studies that purported to demonstrate beta-core fragment-macromolecular complexes in amniotic fluid and pregnancy serum were reporting artifacts introduced by the ammonium thiocyanate used to dissociate beta-core fragment from the putative complex or the in vitro generation of beta-core fragment.