Borderline ovarian tumours: management in the era of fertility-sparing surgery.

Borderline ovarian tumours (BOTs) are ovarian neoplasms characterised by epithelial proliferation, variable nuclear atypia and no evidence of destructive stromal invasion. BOTs account for approximately 15% of all epithelial ovarian cancers. Due to the fact that the majority of BOTs occur in women under 40 years of age, their surgical management often has to consider fertility-sparing approaches. The aim of this mini-review is to discuss the state of the art of fertility-sparing surgery for BOTs with a specific focus on the extent of surgery, post-operative management and fertility.

Cutaneous metastasis from vulvar squamous cell carcinoma: a rare occurrence that should not be forgotten.

Vulvar cancer accounts for 5% of the female genital tract cancers. Cutaneous metastases from vulvar cancer are extremely rare and for this reason, it can be difficult to reach a diagnosis with a consequent delay in the treatment. A systematic literature review of articles on this subject was conducted through a MEDLINE-based search for articles published in English or French. To date, 16 cases (including ours unpublished) of cutaneous metastasis from vulvar cancer have been reported. Cutaneous metastasis can occur from any stage of vulvar cancer, even after a short period. Different treatments have been described but none of them seems to be more effective. In all reported cases the prognosis was very poor. Every time a vulvar cancer survivor shows a suspicious cutaneous lesion, this should be biopsied to exclude skin relapse. Impact statement Cutaneous metastases from vulvar cancer are extremely rare and due to its rarity, a standard treatment has not been established yet. Cutaneous metastasis can occur from any stage of vulvar cancer, even after a short period. In all the reported cases, the prognosis was very poor. Every time a vulvar cancer survivor shows a suspect cutaneous lesion, this should be biopsied to exclude skin relapse.

Intraoperative frozen section risk assessment accurately tailors the surgical staging in patients affected by early-stage endometrial cancer: the application of 2 different risk algorithms.

OBJECTIVE: The aim of this study was to investigate the frozen section (FS) accuracy in tailoring the surgical staging of patients affected by endometrial cancer, using 2 different risk classifications. METHODS/MATERIALS: A retrospective analysis of 331 women affected by type I endometrial cancer and submitted to FS assessment at the time of surgery. Pathologic features were examined on the frozen and permanent sections according to both the GOG33 and the Mayo Clinic algorithms. We compared the 2 models through the determination of Landis and Koch kappa statistics, concordance rate, sensitivity, specificity, positive predictive value, and negative predictive value for each risk algorithm, to assess whether there are differences in FS accuracy depending on the model used. RESULTS: The observed agreement between the frozen and permanent sections was respectively good (k = 0.790) for the GOG33 and optimal (k = 0.810) for the Mayo classification. Applying the GOG33 algorithm, 20 patients (6.7%) were moved to an upper risk status, and 20 (6.7%) were moved to a lower risk status on the permanent section; the concordance rate was 86.5%. With the Mayo Clinic algorithm, discordant cases between frozen and permanent sections were 19 (7.6%), and the risk of lymphatic spread was underestimated only in 1 case (0.4%); the concordance rate was 92.4%. The sensitivity, specificity, positive predictive value, and negative predictive value for the GOG33 were 92%, 94%, 92%, and 93%, whereas with the Mayo algorithm, these were 98%, 91%, 77%, and 99%, respectively. CONCLUSIONS: According to higher correlation rate and observed agreement (92.4% vs 86.5% and k = 0.810 vs 0.790, respectively), the Mayo Clinic algorithm minimizes the number of patients undertreated at the time of surgery than the GOG33 classification and can be adopted as an FS algorithm to tailor the surgical treatment of early-stage endometrial cancer even in different centers.

Targeting tyrosine-kinases in ovarian cancer.

INTRODUCTION: Epithelial ovarian cancer (EOC) is the leading cause of gynaecologic cancer death. Although in some cases initial treatment is effective, most of the women diagnosed with EOC will probably need medical treatment for their disease. There is a critical need to develop effective new strategies for the management of patients with advanced or recurrent EOC, and targeted therapy with tyrosine kinase inhibitors (TKIs) has continued to be an area of active research and development in this setting. AREAS COVERED: This review summarises the available evidence on the use of TKIs in the clinical management of women with EOC. This article consists of material obtained via Medline, PubMed and EMBASE literature searches up to March 2013. EXPERT OPINION: Several Phase I/II and III trials evaluated TKIs in EOC; however, it is difficult to draw conclusions on the efficacy of TKI regimens in these patients. TKIs seem to be better tolerated than conventional chemotherapy with a different toxicity profile. A better understanding of the signalling pathways, the toxicity profiles, the potential pharmacokinetic interactions as well as the identification of predictive biomarkers are needed to better identify a targeted patient population before these agents become part of routine treatment.

Lymphedema microsurgical preventive healing approach for primary prevention of lower limb lymphedema after inguinofemoral lymphadenectomy for vulvar cancer.

OBJECTIVE: Lower limb lymphedema (LLL) is the most disabling adverse effect of surgical treatment of vulvar cancer. This study describes the use of microsurgical lymphatic venous anastomosis (LVA) to prevent LLL in patients with vulvar cancer undergoing inguinofemoral lymph node dissection (ILND). METHODS: The study included 8 patients with invasive carcinoma of the vulva who underwent unilateral or bilateral ILND. Before incision of the skin in the inguinal region, blue dye was injected in the thigh muscles to identify the lymphatic vessels draining the leg. Lymphatic venous anastomosis was performed by inserting the blue lymphatics coming from the lower limb into one of the collateral branches of the femoral vein (telescopic end-to-end anastomosis). An historical control group of 7 patients, which underwent ILND without LVA, was used as comparison. After 1 month from the surgery, all patients underwent a lymphoscintigraphy. RESULTS: In the study group, 4 patients underwent bilateral ILND, and 4 patients underwent unilateral ILND. Blue-dyed lymphatics and nodes were identified in all patients. It was possible to perform LVA in all the patients. The mean (SD) time required to perform a monolateral LVA was 23.1 (3.6) minutes (range, 17-32 minutes). The mean (SD) follow-up was 16.7 (6.2) months; there was only 1 case of grade 1 lymphedema of the right leg. Lymphoscintigraphic results showed a total mean transport index were 9.08 and 14.54 in the study and the control groups, respectively (P = 0.092). CONCLUSIONS: This study shows for the first time the feasibility of LVA in patients with vulvar cancer undergoing ILND. Future studies including larger series of patients should clarify whether this microsurgical technique reduces the incidence of LLL after ILND.

Frozen section pathology at time of hysterectomy accurately predicts endometrial cancer in patients with preoperative diagnosis of atypical endometrial hyperplasia.

OBJECTIVES: A significant number of women diagnosed with atypical endometrial hyperplasia (AEH) on endometrial biopsy will be diagnosed with endometrial cancer (EC) on the hysterectomy specimen at permanent section. Surgical treatment for AEH and EC differ substantially. We have assessed the concordance in EC between frozen and permanent sections on patients undergoing hysterectomy for AEH. MATERIALS AND METHODS: A retrospective review of 66 frozen sections on patients undergoing hysterectomy for AEH was performed. Frozen and permanent section diagnoses were categorized as negative or positive for malignancy. Permanent section carcinomas were classified as low or high risk based on their histopathology, myometrial invasion and differentiation. Correlation between frozen and permanent section and sensitivity, specificity, PPV, NPV and accuracy of frozen section in predicting EC in permanent section were calculated. Likelihood of diagnosing EC on frozen section was compared based on risk stratification at permanent section. RESULTS: Frozen and permanent sections revealed malignancy in 43.9% and 56% of the patients respectively. 94.1% of high risk carcinomas were identified as EC at frozen section as compared to 55% of low risk EC. Concordance was good (κ=0.75). Sensitivity, specificity, NPV, PPV and accuracy in predicting EC at frozen section were 73%, 93.1%, 73% and 93.1% respectively. Carcinomas were detected at frozen section significantly more often if they were at high risk. CONCLUSIONS: The substantial agreement between frozen and permanent sections allows minimizing under- and overtreatment of women undergoing hysterectomy for AEH. High risk EC are efficiently identified in frozen section.

The preoperative diagnosis of borderline ovarian tumors: a review of current literature.

PURPOSE: To evaluate the available information on the preoperative diagnosis of borderline ovarian tumors (BOTs). METHODS: Articles were identified through electronic databases (Medline and EMBASE, MEDLINE, PubMed), no date or language restrictions were placed; relevant citations were hand searched. RESULTS: Women with BOTs are more likely to have no symptom than women with invasive ovarian cancers; however, the type of symptoms is similar in patients with BOTs and invasive ovarian cancers. Up to 61% of women with BOTs have elevated CA-125; CA 19.9 and endoglin are not useful for diagnosing BOTs. Further studies are required to determine whether the measurements of calprotectin, oviductal glycoprotein 1 and growth differentiation factor-15 are useful for diagnosing BOTs. Ultrasonography and magnetic resonance imaging (MRI) are the mainstay for the diagnosis of BOTs. Combining MRI and positron emission tomography may facilitate the identification of BOTs. CONCLUSION: After completion of this article, the reader should be aware of the symptoms of BOTs, the potential role and pitfalls of tumor marker measurement. In addition, the reader will understand the appearance of BOTs at imaging techniques; the reader will be able to compare and combine ultrasonography, MRI and positron emission tomography in diagnosing BOTs. In clinical practice, the reader should be better able to assess whether an ovarian mass is a benign tumor, a BOT or an invasive cancer.

Uterine adenomyosis in persistence of dysmenorrhea after surgical excision of pelvic endometriosis and colorectal resection.

OBJECTIVE: To determine whether the presence of uterine adenomyosis may impair the amelioration of pain symptoms after laparoscopic excision of pelvic endometriosis combined with colorectal resection. STUDY DESIGN: This prospective study included 50 women with bowel endometriosis with or without uterine adenomyosis. Presence of uterine adenomyosis was investigated by magnetic resonance imaging. Patients underwent excision of pelvic endometriosis and colorectal resection; some patients with focal adenomyosis underwent uterine surgery. Pain symptoms and gastrointestinal complaints were evaluated before surgery and at 6, 12 and 18 months' follow-up. RESULTS: At 6-month follow-up, dysmenorrhea significantly improved in women without uterine adenomyosis and in those with adenomyosis that was excised at surgery; this improvement persisted at 18 months' followup. No significant improvement in dysmenorrhea was observed in women with adenomyosis not excised at surgery. Deep dyspareunia and chronic pelvic pain significantly improved at follow-up in all study groups. Most of gastrointestinal symptoms improved or disappeared at 6 months' follow-up; the improvement in gastrointestinal function persisted at 18 months' follow-up. CONCLUSION: Excision of pelvic endometriosis combined with bowel resection significantly improves chronic pelvic pain, dyspareunia and gastrointestinal symptoms; however, the presence of uterine adenomyosis may determine persistence of dysmenorrhea.

Transvaginal ultrasonography combined with water-contrast in the rectum in the diagnosis of rectovaginal endometriosis infiltrating the bowel.

This prospective study evaluated the efficacy of transvaginal ultrasonography combined with water-contrast in the rectum (RWC-TVS) in the diagnosis of rectal infiltration in 35 women with rectovaginal endometriosis; ultrasonographic findings were compared with surgery and histology. The sensitivity of RWC-TVS in identifying rectal infiltration reaching at least the muscular layer was 100%, the specificity was 85.7%, the positive predictive value was 91.3%, and the negative predictive value was 100%. In 4 of 5 (80.0%) nodules reaching the submucosa, the depth of infiltration was underestimated by RWC-TVS. The RWC-TVS reliably determined the largest diameter of the endometriotic nodules and was well tolerated by the patients.