Fertility-sparing surgery of cervical cancer >2 cm (International Federation of Gynecology and Obstetrics 2009 stage IB1-IIA) after neoadjuvant chemotherapy.

OBJECTIVE: To assess the feasibility, safety, oncological, and obstetric outcomes in patients with cervical tumors >2 cm treated with neoadjuvant chemotherapy in preparation for abdominal radical trachelectomy. METHODS: A retrospective analysis of patients with cervical cancer >2 cm (up to 6 cm) was conducted in patients who were selected to receive neoadjuvant chemotherapy before abdominal radical trachelectomy. Surgical and clinical outcomes were examined in relation to radiological and pathological results. In addition, obstetric outcomes were described. The Mann-Whitney U test and Fisher's exact test were performed to compare radiological findings between successful and unsuccessful abdominal radical trachelectomy procedures. International Federation of Gynecology and Obstetrics (FIGO) 2009 staging classification was used for this study. RESULTS: A total of 19 women were treated with neoadjuvant chemotherapy for cervical tumors >2 cm at our institution between May 2006 and July 2018. The median age was 28 years (range 19-36). The distribution of FIGO stages was seven patients stage IB1 (37%), 10 patients stage IB2 (53%), and two patients (10%) stage IIA. Mean clinical tumor size was 4.4 cm (range 3.5-6.0). Histology revealed 74% cases of squamous cell carcinoma. The remaining patients had adenocarcinoma (21%) and only one patient had clear cell adenocarcinoma (5%). Chemotherapy consisted of six weekly cycles of cisplatin (70 mg/m2) and paclitaxel (70 mg/m2). In 15 of the 19 patients (74%) fertility was successfully preserved. In the four patients in whom fertility preservation failed, one patient had stable disease after three cycles and did not meet the criteria for fertility-sparing surgery and three patients had intra- or post-operative indications for adjuvant therapy. Three of the 19 patients (15.7%) had a relapse, two of whom died. One case was in the group of successful abdominal radical trachelectomy. CONCLUSION: Neoadjuvant chemotherapy followed by fertility-sparing surgery may be a feasible and safe option in select patients with cervical tumors >2 cm. Unfavorable prognostic factors are defined as non-responsiveness and non-squamous pathology, which can help in patient selection for fertility-sparing surgery.

Genomic Characterization of Vulvar (Pre)cancers Identifies Distinct Molecular Subtypes with Prognostic Significance.

Purpose: Vulvar cancer (VC) can be subclassified by human papillomavirus (HPV) status. HPV-negative VCs frequently harbor TP53 mutations; however, in-depth analysis of other potential molecular genetic alterations is lacking. We comprehensively assessed somatic mutations in a large series of vulvar (pre)cancers.Experimental Design: We performed targeted next-generation sequencing (17 genes), p53 immunohistochemistry and HPV testing on 36 VC and 82 precursors (sequencing cohort). Subsequently, the prognostic significance of the three subtypes identified in the sequencing cohort was assessed in a series of 236 VC patients (follow-up cohort).Results: Frequent recurrent mutations were identified in HPV-negative vulvar (pre)cancers in TP53 (42% and 68%), NOTCH1 (28% and 41%), and HRAS (20% and 31%). Mutation frequency in HPV-positive vulvar (pre)cancers was significantly lower (P = 0.001). Furthermore, a substantial subset of the HPV-negative precursors (35/60, 58.3%) and VC (10/29, 34.5%) were TP53 wild-type (wt), suggesting a third, not-previously described, molecular subtype. Clinical outcomes in the three different subtypes (HPV+, HPV-/p53wt, HPV-/p53abn) were evaluated in a follow-up cohort consisting of 236 VC patients. Local recurrence rate was 5.3% for HPV+, 16.3% for HPV-/p53wt and 22.6% for HPV-/p53abn tumors (P = 0.044). HPV positivity remained an independent prognostic factor for favorable outcome in the multivariable analysis (P = 0.020).Conclusions: HPV- and HPV+ vulvar (pre)cancers display striking differences in somatic mutation patterns. HPV-/p53wt VC appear to be a distinct clinicopathologic subgroup with frequent NOTCH1 mutations. HPV+ VC have a significantly lower local recurrence rate, independent of clinicopathological variables, opening opportunities for reducing overtreatment in VC. Clin Cancer Res; 23(22); 6781-9. ©2017 AACR.

A Controlled Study on Vaginal Blood Flow During Sexual Arousal Among Early-Stage Cervical Cancer Survivors Treated With Conventional Radical or Nerve-Sparing Surgery With or Without Radiotherapy.

OBJECTIVE: Sexual problems among cervical cancer survivors may in part be caused by reduced vaginal blood flow due to damaged hypogastric nerves during radical hysterectomy with pelvic lymphadenectomy and/or by radiation-induced vaginal changes after pelvic radiotherapy. A nerve-sparing modification of radical hysterectomy (NSRH) may preserve vaginal blood flow. Vaginal blood flow during sexual arousal was compared between different treatment modalities. METHODS: We investigated premenopausal women treated for early-stage cervical cancer with radical hysterectomy (n = 29), NSRH (n = 28), NSRH with radiotherapy (n = 14), and controls (n = 31). Genital arousal and subjective sexual arousal in response to sexual stimuli were measured using vaginal photoplethysmography and a questionnaire. Results were compared by using a between-study (treatment groups) by within-study (stimulus) design. RESULTS: Participants were aged 29 to 51 years (mean, 42 years) and at 1 to 14 years (mean, 5 years) after treatment. Measured vaginal blood flow in women treated with NSRH was similar to controls. Women treated with radical hysterectomy had a significantly lower vaginal blood flow compared with controls overall and lower compared with the NSRH group during sexual stimulation. Women treated with radiotherapy had a vaginal blood flow intermediate between the other groups without significant differences. The erotic films were equally effective in enhancing subjective sexual arousal among treatment groups. CONCLUSIONS: Cervical cancer treatment with radical hysterectomy disrupts the vaginal blood flow response, and this may be prevented by conducting an NSRH. Treatment with radiotherapy did not significantly impact vaginal blood flow, but further investigation is needed with a larger sample.

The effect of a dopamine antagonist on conditioning of sexual arousal in women.

RATIONALE: Dopamine (DA) plays a key role in reward-seeking behaviours. Accumulating evidence from animal and human studies suggests that human sexual reward learning may also depend on DA transmission. However, research on the role of DA in human sexual reward learning is completely lacking. OBJECTIVES: To investigate whether DA antagonism attenuates classical conditioning of sexual response in humans. METHODS: Healthy women were randomly allocated to one of two treatment conditions: haloperidol (n = 29) or placebo (n = 29). A differential conditioning paradigm was applied with genital vibrostimulation as unconditional stimulus (US) and neutral pictures as conditional stimuli (CSs). Genital arousal was assessed, and ratings of affective value and subjective sexual arousal were obtained. RESULTS: Haloperidol administration affected unconditional genital responding. However, no significant effects of medication were found for conditioned responding. CONCLUSIONS: No firm conclusions can be drawn about whether female sexual reward learning implicates DA transmission since the results do not lend themselves to unambiguous interpretation.

The Influence of Emotion Upregulation on the Expectation of Sexual Reward.

INTRODUCTION: Emotion regulation research has shown successful altering of unwanted aversive emotional reactions. Cognitive strategies can also downregulate expectations of reward arising from conditioned stimuli, including sexual stimuli. However, little is known about whether such strategies can also efficiently upregulate expectations of sexual reward arising from conditioned stimuli, and possible gender differences therein. AIM: The present study examined whether a cognitive upregulatory strategy could successfully upregulate sexual arousal elicited by sexual reward-conditioned cues in men and women. METHODS: Men (n = 40) and women (n = 53) participated in a study using a differential conditioning paradigm, with genital vibrostimulation as unconditioned stimulus (US) and sexually relevant pictures as conditional stimuli. MAIN OUTCOME MEASURES: Penile circumference and vaginal pulse amplitude were assessed and ratings of US expectancy, affective value, and sexual arousal value were obtained. Also a stimulus response compatibility task was included to assess automatic approach and avoidance tendencies. RESULTS: Evidence was found for emotion upregulation to increase genital arousal response in the acquisition phase in both sexes, and to enhance resistance to extinction of conditioned genital responding in women. In men, the emotion upregulatory strategy resulted in increased conditioned positive affect. CONCLUSION: The findings support that top-down modulation may indeed influence conditioned sexual responses. This knowledge may have implications for treating disturbances in sexual appetitive responses, such as low sexual arousal and desire.

d-Cycloserine reduces context specificity of sexual extinction learning.

BACKGROUND: d-Cycloserine (DCS) enhances extinction processes in animals. Although classical conditioning is hypothesized to play a pivotal role in the aetiology of appetitive motivation problems, no research has been conducted on the effect of DCS on the reduction of context specificity of extinction in human appetitive learning, while facilitation hereof is relevant in the context of treatment of problematic reward-seeking behaviors. METHODS: Female participants were presented with two conditioned stimuli (CSs) that either predicted (CS+) or did not predict (CS-) a potential sexual reward (unconditioned stimulus (US); genital vibrostimulation). Conditioning took place in context A and extinction in context B. Subjects received DCS (125mg) or placebo directly after the experiment on day 1 in a randomized, double-blind, between-subject fashion (Placebo n=31; DCS n=31). Subsequent testing for CS-evoked conditioned responses (CRs) in both the conditioning (A) and the extinction context (B) took place 24h later on day 2. Drug effects on consolidation were then assessed by comparing the recall of sexual extinction memories between the DCS and the placebo groups. RESULTS: Post learning administration of DCS facilitates sexual extinction memory consolidation and affects extinction's fundamental context specificity, evidenced by reduced conditioned genital and subjective sexual responses, relative to placebo, for presentations of the reward predicting cue 24h later outside the extinction context. CONCLUSIONS: DCS makes appetitive extinction memories context-independent and prevents the return of conditioned response. NMDA receptor glycine site agonists may be potential pharmacotherapies for the prevention of relapse of appetitive motivation disorders with a learned component.

Synergistic effects of the sesquiterpene lactone, EPD, with cisplatin and paclitaxel in ovarian cancer cells.

BACKGROUND: Ovarian cancer remains still the leading cause of death of gynecological malignancy, in spite of first-line chemotherapy with cisplatin and paclitaxel. Although initial response is favorably, relapses are common and prognosis for women with advanced disease stays poor. Therefore efficacious approaches are needed. METHODS: Previously, an anti-cancer agent, EPD exhibited potent cytotoxic effects towards ovarian cancer and not towards normal cells. Cell viability and cell cycle analysis studies were performed with EPD, in combination with cisplatin and/or paclitaxel, using the ovarian carcinoma cell lines: SK-OV-3, OVCAR-3, JC, JC-pl and normal fibroblasts. Cell viability was measured using Presto Blue and cell cycle analysis using a flow cytometer. Apoptosis was measured in JC and JC-pl , using the caspase 3 assay kit. RESULTS: In JC-pl, SK-OV-3 and JC, synergistic interactions between either EPD and cisplatin or EPD and paclitaxel were observed. For the first time the effects of EPD on the cell cycle of ovarian cancer cells and normal cells was studied. EPD and combinations of EPD with cisplatin and/ or paclitaxel showed cell cycle arrest in the G2/M phase. The combination of EPD and cisplatin showed a significant synergistic effect in cell line JC-pl, while EPD with paclitaxel showed synergistic interaction in JC. Additionally, synergistic drug combinations showed increased apoptosis. CONCLUSIONS: Our results showed a synergistic effect of EPD and cisplatin in an ovarian drug resistant cell line as well as a synergistic effect of EPD and paclitaxel in two other ovarian cell lines. These results might enhance clinical efficacy, compared to the existing regimen of paclitaxel and cisplatin.

Clinical characteristics associated with development of recurrence and progression in usual-type vulvar intraepithelial neoplasia.

OBJECTIVE: To identify clinical characteristics associated with recurrence and progression in patients with usual vulvar intraepithelial neoplasia (uVIN), which may function as prognostic factors and aid in the treatment of patients with human papillomavirus (HPV)-related disease of the genital tract. METHODS: A retrospective chart review was performed in 73 patients with uVIN treated at the Leiden University Medical Center between 1990 and 2012. All medical records were reviewed for demographics, treatment type, pathology reports, and recurrence and progression rates. RESULTS: The mean age of diagnosis was 43 years, and uVIN was symptomatic in 60.1% of the patients. The median follow-up time was 49 months. High-risk HPV was found in 86.3% of the patients. Smoking was reported in 76.8% of the patients. Eleven of 73 patients were immune compromised. Multicentric HPV-related disease of the cervix or vagina was reported in 75.3% of the patients. Recurrences were diagnosed in 50.7% of the patients after first treatment type that consisted of excision (45.2%), laser (34.2%), imiquimod (8.2%), and combination of excision and laser (12.3%). Higher recurrence rates were only correlated with multifocality of uVIN lesions. Excision, imiquimod therapy, and unifocal lesions showed an increased recurrence-free survival. Human papillomavirus type, smoking, multicentric disease, use of topical steroids, and positive surgical borders were not related to a shorter recurrence-free survival. Progression into vulvar carcinoma occurred in 11 (15.1%) of the patients, 4 of whom were immune compromised. These patients showed a shorter progression-free survival of 54 versus 71.5 months. CONCLUSION: There are no clinical characteristics that form prognostic factors in uVIN, except for multifocality of lesions, which is correlated with a higher recurrence rate. Furthermore, progression of uVIN to carcinoma was accelerated and increased in immune-compromised patients, suggesting that studies of local immunity in uVIN may reveal potentialprognostic factors and aid in the development of new treatment modalities.

Potent cytotoxic effects of Calomeria amaranthoides on ovarian cancers.

BACKGROUND: Ovarian cancer remains the leading cause of death from gynaecological malignancy. More than 60% of the patients are presenting the disease in stage III or IV. In spite of combination of chemotherapy and surgery the prognosis stays poor for therapy regimen. METHODS: The leaves of a plant endemic to Australia, Calomeria amaranthoides, were extracted and then fractionated by column chromatography. In vitro cytotoxicity tests were performed with fractions of the plant extract and later with an isolated compound on ovarian cancer cell lines, as well as normal fibroblasts at concentrations of 1-100 µg/mL (crude extract) and 1-10 µg/mL (compound). Cytotoxicity was measured after 24, 48 and 72 hours by using a non-fluorescent substrate, Alamar blue.In vivo cytotoxicity was tested on ascites, developed in the abdomen of nude mice after inoculation with human OVCAR3 cells intraperitoneally. The rate of change in abdomen size for the mice was determined by linear regression and statistically evaluated for significance by the unpaired t test. RESULTS: Two compounds were isolated by chromatographic fractionation and identified by 1H-NMR, 13C-NMR and mass spectrometry analyses, EPD, an α-methylene sesquiterpene lactone of the eremophilanolide subtype, and EPA, an α-methylene carboxylic acid.Cytotoxicity of EPD for normal fibroblasts at all time points IC50 was greater than 10 µg/mL, whereas, for OVCAR3 cells at 48 hours IC50 was 5.3 µg/mL (95% confidence interval 4.3 to 6.5 µg/mL).Both, the crude plant extract as well as EPD killed the cancer cells at a final concentration of 10 µg/mL and 5 µg/mL respectively, while in normal cells only 20% cell killing effect was observed. EPA had no cytotoxic effects.Changes in abdomen size for control versus Cisplatin treated mice were significantly different, P = 0.023, as were control versus EPD treated mice, P = 0.025, whereas, EPD versus Cisplatin treated mice were not significantly different, P = 0.13. CONCLUSIONS: For the first time both crude plant extract from Calomeria amaranthoides and EPD have been shown to have potent anti-cancer effects against ovarian cancer.

Value of an objective assessment tool in the operating room.

BACKGROUND: Concerns about the achievement of surgical proficiency during residency are increasing. To objectify surgical skills, the Objective Structured Assessment of Technical Skills (OSATS) was developed and proven valid, feasible and reliable for use in laboratory settings. This study aimed to evaluate the value of this tool for intraoperative use. METHODS: Residents were assessed with an OSATS after every procedure they performed as the primary surgeon during a 3-month clinical rotation in gynecological surgery. We mapped individual learning curves (OSATS scores plotted against experience) and established the average procedure-specific learning curve. We used linear mixed models to assess the relation between performance and experience. RESULTS: Nine residents were recruited and 319 OSATS analyzed. Individual learning curves revealed progression beyond 24 of 30 OSATS points for 7 residents. Performance on the average procedure improved with experience, and the OSATS score increased by an average of 1.10 points per assessed procedure (p=0.008, 95% confidence interval 0.44-1.77). Median OSATS scores ranged from 18 to 30 among the 21 assessors. CONCLUSION: Intraoperative implementation of OSATS seems to offer important advantages: structured feedback is facilitated, and learning curves enable insight into individual progression. However, doubts have been raised about the objectivity of the tool. Therefore, caution is warranted in using it for graduation and certification.

Surgical staging and treatment of early ovarian cancer: long-term analysis from a randomized trial.

A long-term follow-up analysis of the randomized clinical trial Adjuvant Chemotherapy in Ovarian Neoplasm (ACTION) from the European Organization for Research and Treatment of Cancer was undertaken to determine whether the original results with a median follow-up of 5.5 years could be verified after longer follow-up with more events. In the ACTION trial, 448 patients with early ovarian cancer were randomly assigned, after surgery, to adjuvant chemotherapy or to observation (no further treatment). The original analysis found that adjuvant chemotherapy improved recurrence-free survival but not overall survival and found in a subgroup analysis that completeness of surgical staging was an independent prognostic factor, with better recurrence-free and overall survival among those with complete (optimal) surgical staging. After a median follow-up of 10.1 years, we analyzed the more mature data from the ACTION trial and found support for most of the main conclusions of the original analysis, except that overall survival after optimal surgical staging was improved, even among patients who received adjuvant chemotherapy (hazard ratio of death = 1.89, 95% confidence interval = 0.99 to 3.60; overall two-sided log-rank test P = .05). More cancer-specific deaths were observed among nonoptimally staged patients (40 [27%] of the 147 deaths in the observation arm and 11 [14%] of the 76 deaths in the adjuvant chemotherapy arm) than among optimally staged patients (seven [9%] of the 75 deaths in the observation arm and 11 [14%] of the 76 deaths in the adjuvant chemotherapy arm) (two-sided chi(2) test for heterogeneity, P = .06). Thus, completeness of surgical staging in patients with early ovarian cancer was found to be statistically significantly associated with better outcomes, and the benefit from adjuvant chemotherapy appeared to be restricted to patients with nonoptimal surgical staging.

Cognitive-affective correlates and predictors of superficial dyspareunia.

This study investigated the role of cognitive-affective variables related to sexuality, chronic pain, individual and relational well-being in superficial dyspareunia. Although symptomatic women (n = 80) differed from complaint-free controls (n = 62) on all variables, sexuality related measures had the most important contribution into the prediction of group membership. Dyspareunia subgroups based on the presence/absence of a concomitant diagnosis of provoked vestibulodynia were only distinguishable on pain intensity but not on variables related to sexuality and psychological well-being. The present findings underscore the relevance of psychosexual factors in women with superficial dyspareunia.

Human papilloma virus specific T cells infiltrating cervical cancer and draining lymph nodes show remarkably frequent use of HLA-DQ and -DP as a restriction element.

Human papillomavirus (HPV)-induced malignancies are frequently infiltrated by lymphocytes. To comprehend the contribution of HPV-specific T cells in this anti-tumor response we developed a method that allowed the analysis of the presence and specificity of cervix-infiltrating and draining lymph node resident T cells in a group of 74 patients with cervical malignancies, 54 of which were induced by HPV16 or HPV18. We detected the presence of HPV16 or HPV18-specific T cells in at least 23 of the 54 HPV-16 or -18 positive patients, and not in the 20 controls. Detailed studies resulted in the identification of 17 novel CD4+ and CD8+ T cell epitopes and their HLA-restriction elements, and also revealed that the HPV-specific immune response was aimed at both E6 and E7 and showed no preferential recognition of immunodominant regions. Unexpectedly, the vast majority of the CD4+ T cell epitopes were presented in the context of the less abundantly expressed HLA-DQ and HLA-DP molecules. Since the identified T cell epitopes constitute physiological targets in the immune response to HPV16 and HPV18 positive tumors they will be valuable for detailed studies on the interactions between the tumor and the immune system. This is crucial for the optimization of cancer immunotherapy in patients with pre-existing tumor-immunity.

Interobserver agreement on interpreting hand drawings of colposcopy in women with borderline cytology to predict high-grade lesions.

OBJECTIVE: To assess the interobserver agreement on interpreting hand drawings as a colposcopic image recording technique in women with borderline cytology and to assess the correlation between colposcopic impression and histological outcome. METHODS: We used colposcopic documentation and histology from a cohort study of women with borderline dyskaryosis. Four gynecologists and four residents scored the same 30 colposcopic documentation forms. RESULTS: There is a good interobserver agreement on classifying colposcopic hand drawings as high-grade lesions (average kappa 0.58). The interobserver agreement on interpreting colposcopic image was higher for the more highly experienced gynecologists than for the residents. The agreement between colposcopic impression and histological outcome is poor (kappa 0.17) among the observers. CONCLUSIONS: Hand drawings are a reliable recording technique of interpreting colposcopic impression documented as high-grade lesion. However, the correlation between colposcopic impression and histological outcome is still poor in women with minor cytological abnormalities.

Cosmetic results of lower midline abdominal incision: Donati stitches versus a continuous intracutaneous suture in a randomized clinical trial.

BACKGROUND: The objective of this study was to compare the cosmetic outcome of two different closing techniques for lower midline abdominal incisions: a continuous intracutaneous suture versus interrupted Donati stitches. METHODS: Eighty patients undergoing gynecological surgery through a lower midline abdominal incision were randomized. The cosmetic outcome of the scar was assessed by independent observers and the patients at 8 days and 4-6 months after the operation using visual analog scales and a validated scoring system for hypertrophy, width, color, and cross-hatching. Patients also completed a visual analog scale for postoperative pain on both occasions. The accumulated data were statistically evaluated using two-sided chi 2, Student's t, or Mann-Whitney tests with a confidence interval of 95%. RESULTS: Closing a lower midline abdominal laparotomy wound with an absorbable intracutaneous suture did not take more time than using Donati stitches. Laparotomy scores were only significantly better in the intracutaneous group at the first assessment, one week after the operation. The cosmetic visual analog scale scores by both independent observers and patients were slightly better in the intracutaneous group but the difference was not statistically significant. There was also no significant difference between visual analog scale scores for pain felt around the scar. CONCLUSIONS: This study shows that in the opinion of both independent observers and patients, scar cosmetics are not significantly different when using Donati skin sutures or an intracutaneous suture to close a lower midline laparotomy wound. The two methods do not differ either in time-consuming aspects or postoperative pain perception.

Follow-up after incomplete hysteroscopic removal of uterine fibroids.

BACKGROUND: In this observational study, we analysed whether a period of wait and see was reasonable following incomplete removal of submucous fibroids, with regard to symptoms of abnormal uterine bleeding, and whether factors predicting subsequent surgery could be identified. METHODS: In 3 affiliated hospitals, patients with incomplete removal of submucous fibroids, treated with hysteroscopic myomectomy for abnormal uterine bleeding, between January 1997 and January 2005, were followed over time. Using life-table analysis (Kaplan-Meier method), the cumulative proportion of women having surgery-free survival following incomplete removal of submucous fibroids was calculated. Cox-proportional hazard analyses were used to analyse relationships of variables with recurrence of symptoms. RESULTS: Forty-one consecutive patients met the inclusion criteria, and were followed over time. The mean age was 42.5 years (range 27-55). The majority of patients with incomplete removal of submucous fibroids were diagnosed with type 2 fibroids. Termination of the procedure before complete removal was achieved, was principally caused by reaching the maximum fluid deficit (90.2%). The surgery-free percentages were 70.2% (95%-CI: 55.3-85.1) at 1 year, 54.8% (95%-CI: 38.1-70.7) at 2 years, and 44.2% (95%-CI: 26.9-61.5) at 3 years. Size of fibroid (diameter) pre-operatively turned out to be of statistically significant influence, with a hazard ratio of 1.762 (95%-CI: 1.114-2.787) per cm increase in diameter (p=0.016). CONCLUSIONS: The results indicate that incomplete removal does not always seem to necessitate subsequent surgery. Instead of subsequent surgery immediately post-operatively, a wait and see policy is worth considering after incomplete removal.

Treatment of patients with early epithelial ovarian cancer.

PURPOSE OF REVIEW: During 2003, the first randomized trials were published comparing adjuvant platin-based chemotherapy versus no treatment in early epithelial ovarian cancer. RECENT FINDINGS: Recent findings of the European Organisation for Research and Treatment of Cancer Adjuvant ChemoTherapy In Ovarian Neoplasm and International Collaborative Ovarian Neoplasm-1 trials showed an improvement of overall survival of 8% in patients treated with adjuvant platin-based chemotherapy compared with observation. In a subgroup analysis, in 150 optimally surgically staged patients of the European Organisation for Research and Treatment of Cancer Adjuvant ChemoTherapy In Ovarian Neoplasm trial, there appears to be no benefit of adjuvant chemotherapy. In past years, it has been shown that degree of differentiation is a much stronger predictor of recurrence in early ovarian cancer than International Federation of Gynaecology and Obstetrics subclassification (Ia, Ib, Ic). It has also been shown that patients with bilateral tumors (Ib) have the same prognosis as International Federation of Gynaecology and Obstetrics stage Ic patients. SUMMARY: During the past year, it has been shown that platin-based adjuvant chemotherapy improves recurrence-free and overall survival in early epithelial ovarian cancer. It should be emphasized, however, that this was demonstrated in patients in whom the true nature of early stage disease was doubtful in many patients due to incomplete surgical staging. In a subgroup of patients who are optimally surgically staged, adjuvant chemotherapy may be less effective. Theoretically, only a future trial randomizing optimal surgical staging versus adjuvant chemotherapy may be able to provide definitive conclusions, but such a trial would be almost impossible to conduct. In the meantime, optimal staging is advocated in all patients who are fit enough to undergo this procedure. Degree of differentiation should be incorporated in a new International Federation of Gynaecology and Obstetrics classification for stage I disease and in clinical decision making.

Detection of cervical intraepithelial neoplasia in women with atypical squamous or glandular cells of undetermined significance cytology: a prospective study.

BACKGROUND: (1) To assess the prevalence of histologically confirmed cervical intraepithelial neoplasia in patients with cervical smears diagnosed as atypical squamous or glandular cells of undetermined significance. (2) To evaluate the role of colposcopy and the presence of human papillomavirus in detecting underlying cervical intraepithelial neoplasia. MATERIALS AND METHODS: In this prospective cohort, 148 women with atypical squamous or glandular cells of undetermined significance were evaluated by colposcopy, histological sampling, and human papillomavirus deoxyribonucleic acid testing. RESULTS: Histological diagnosis of >/= cervical intraepithelial neoplasia II was found in 10/148 women. Women with a histological >/= cervical intraepithelial neoplasia II had a higher prevalence of >/= two abnormal quadrants (90% vs. 38%/= cervical intraepithelial neoplasia II.