Mario Valenzano Menada

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.

Triptorelin improves intestinal symptoms among patients with colorectal endometriosis

⁎ Corresponding author. Department of Obstetrics and Gynecology, San Martino Hospital, Largo R. Benzi 1, 16132 Genoa, Italy. Tel./fax: +39 10 511 525. E-mail address: dr@simoneferrero.com (S. Ferrero). Little attention has been given to the role of hormonal therapies in treating symptoms caused by bowel endometriosis [1]. The aim of the present open-label prospective study was to evaluate the effects of GnRH analogues (GnRH-a) on pain and intestinal symptoms among patients with colorectal endometriosis. Multidetector computerized tomographyenteroclysis (MDCT-e)was used to determine the presence and severity of colorectal endometriosis [2]. Inclusion criteria for the study were reproductive age, pain and gastrointestinal symptoms suggestive of bowel endometriosis (persisting for at least 12 months), and colorectal nodules infiltrating at least the muscularis propria of the bowel. Exclusion criteria were stenosis of the bowel lumen greater than 60% and presence of endometriotic nodules located on the cecum or the ileum. Study participants received depot intramuscular injections of the 3-month formulation of triptorelin (11.25 mg; Decapeptyl, Ipsen Pharma, Milan, Italy) and oral tibolone (2.5 mg daily; Livial, Organon, Rome, Italy) for 12 months. Patients were allowed to take nonsteroidal anti-inflammatory drugs for the treatment of pain (550 mg naproxen sodium tablet; Synflex Forte 550, Recordati Industria Chimica e Farmaceutica, Milan, Italy) and lactulose (dose of 10 g per 15 mL; Laevolac, Roche, Milan, Italy) for the treatment of constipation. Presence and intensity of symptoms were evaluated before starting the treatment andafter 6 and12 months of treatment. At completion, the overall degree of patient satisfactionwith the treatmentwas determined by responses given to the following question: “Taking into consideration the variations in pain symptoms, overall well-being, and quality of life, as well as any adverse effects experienced, howwould you define the level of satisfaction with your treatment?” [3]. Patients were also asked whether their intestinal symptoms changed during treatment. The local Institutional Review Board approved the study protocol. Patients were informed that surgery is the standard treatment for symptomatic bowel endometriosis [1,4] and the potential benefits and complications of surgery were explained in detail. All study subjects wished to avoid or postpone surgery and requested amedical therapy. Patients were also told that hormonal therapies are not expected to be definitely curative of endometriosis [5]. Study participants provided written informed consent. Variations in grading of symptoms between baseline and follow-up were compared using the paired t test and the signed rank test according to data distribution. Eighteen women were included in the study, with a mean age of 36.1±4.7 years. The larger endometriotic bowel nodule was located on the sigmoid in9women,on the rectosigmoid junction in5women, and on the rectum in 4 women. The mean estimated size of the larger colorectal nodulewas2.2±0.6 cmand themeanestimatedstenosisof the bowel lumenwas42.0%±9.7%.At the 12-monthassessment of the effects of therapy on the symptoms, 13 (72.2%) women were very satisfied or satisfied, 2 (11.1%) were uncertain, and 3 (16.7%) were dissatisfied. Intestinal symptomswere unchanged during treatment in 7 (38.9%) women, while 11 patients (61.1%) reported some improvements in intestinal function. Table 1 shows that patients with symptoms mimicking diarrhea-predominant irritable bowel syndrome (IBS-D) reported improvements in intestinal symptoms significantly more frequently than those with symptoms mimicking constipationpredominant irritable bowel syndrome (IBS-C; 100.0% vs 14.3,P=0.003). The severity of dysmenorrhea, nonmenstrual pelvic pain, deep dyspareunia, anddyscheziawasmeasuredusing a 10-cmvisual analogue scale (VAS). The treatment significantly decreased the intensity of pain symptoms (Table 2). The severity of the intestinal symptoms was measured using a symptom analogue scale questionnaire (1 indicated the absence of the symptom; 10 indicated the highest severity of the symptom). IBS-D, intestinal cramping, abdominal bloating, and passage of mucus improved during treatment; no significant change was observed in IBS-C and feeling of incomplete evacuation (Table 2). The number of naproxen sodium tablets used by patients decreased during treatment; the number of lactulose doses used by patients did not change during treatment (Table 2). Fifteen women (83.3%) reported at least 1 adverse effect (hot flushes, n=6; vaginal bleeding, n=6; sweating episodes, n=3; vaginal dryness and superficial dyspareunia, n=2; nervousness and irritability, n=2; loss of libido, n=2; weight gain, n=2; sleeplessness, n=1; difficulty in concentrating, n=1; fatigue, n=1). At the completion of the study, 7 patients (38.9%) continued the treatment with triptorelin and tibolone; 50.0% of the patients with IBS-D continued the treatment with triptorelin versus 14.3% of the patients with IBS-C (P=0.282).

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.

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

PurposeTo evaluate the available information on the preoperative diagnosis of borderline ovarian tumors (BOTs).MethodsArticles were identified through electronic databases (Medline and EMBASE, MEDLINE, PubMed), no date or language restrictions were placed; relevant citations were hand searched.ResultsWomen 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.ConclusionAfter 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.

Spontaneous regression of transplacental metastases from maternal melanoma in a newborn: Case report and review of the literature

We describe a rare case of transplacental-transmitted maternal melanoma to the placenta and foetus during the second pregnancy of a 28-year-old woman. She was aware of a greyish–brown nodular lesion on the right gluteus during her first pregnancy. On histological examination, this lesion resulted to be an amelanocitic melanoma. Breast metastases occurred during her second pregnancy, 18 months after the surgical excision; an emergency Caesarean section performed for the recrudement of her clinical conditions confirmed widespread metastases to the liver, spleen and peritoneum. The patient died 2 weeks after delivery. The newborn, at 3 months of age, presented metastases secondary to maternal melanoma, which were resistant to chemotherapy. The disease regressed spontaneously and the child is now 24 months, alive in complete remission.

Evaluation of endometrial thickness in hormone receptor positive early stage breast cancer postmenopausal women switching from adjuvant tamoxifen treatment to anastrozole.

Evaluation of endometrial thickness by transvaginal ultrasonography (TVUS) in postmenopausal estrogen receptor positive breast cancer patients treated with anastrozole after tamoxifen therapy. This study included 70 postmenopausal estrogen receptor positive breast cancer patients who switched to anastrozole after tamoxifen; patients had endometrial thickness >4mm and no endometrial malignancy. Endometrial thickness was measured after anastrozole treatment. Endometrial thickness during anastrozole therapy was lower than after tamoxifen therapy (p<0.001); the mean reduction in endometrial thickness was 4.5mm (+/-3.0). Cystic endometrial appearance was more frequent in patients under tamoxifen than in those under anastrozole (p<0.001). Duration of tamoxifen therapy was not correlated to the endometrial thickness at the time of its suspension. Duration of tamoxifen therapy and endometrial thickness at the time of tamoxifen suspension was correlated to the relative reduction of endometrial thickness during anastrozole therapy. Anastrozole reverses tamoxifen-induced increased endometrial thickness and sonographic endometrial cystic appearance.

Breast cancer with synchronous massive metastasis in the uterine cervix: a case report and review of the literature.

IntroductionMetastatic breast cancer is rare in the female genital tract, and when present it more commonly tends to involve ovary or endometrium; uterine cervix is only occasionally involved. This condition poses differential diagnostic problems in the settings of clinical and pathological investigations.Case presentationAn asymptomatic 78-year-old woman came to our attention in the context of routine gynecological surveillance; clinical examination disclosed enlarged uterine body and cervix. Our patient then underwent computed tomography and magnetic resonance imaging that outlined the possibility of cervical cancer with parametrial involvement. Moreover, a suspect mass was found on the mammogram in the left breast. Breast surgical excision was performed, which revealed invasive breast carcinoma, while synchronous cervical biopsy discovered distant metastasis in the uterine cervix. On histological examination, both lesions showed non-cohesive architectural pattern consistent with lobular morphology; anyway, to rule out primary poorly differentiated cervical cancer, appropriate immunohistochemical panel was performed, which confirmed the mammary derivation of the tumor. Due to disseminate disease, the patient underwent multisystemic medical treatment including radiotherapy, chemotherapy and hormone therapy, and she is still alive at 30-month follow-up.DiscussionGenital tract metastases in patients with known breast carcinoma can present with abnormal vaginal bleeding, but they often are asymptomatic. Therefore, only strict gynecological surveillance of these patients can permit early detection of these secondary lesions. Aggressive treatment of isolated cervical metastasis should be performed when feasible; otherwise, systemic chemotherapy with taxane could be sufficient in increasing survival. It should be emphasized that, in most cases, only accurate immunohistochemical investigation, particularly if performed on the primary lesion as well, can solve differential diagnostic problems and allow the clinician to establish appropriate treatment.

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.

Sorafenib for ovarian cancer.

Introduction: Sorafenib is an unselective inhibitor of multiple kinases which has demonstrated clinical advantage in renal cancer and hepatocellular carcinoma. It inhibits tumor proliferation by targeting receptor accessory factor (Raf) kinase isoforms, inhibiting receptor tyrosine kinases of a variety of pro-angiogenic factors and of several receptor tyrosine kinases involved in neovascularization and tumor development. Areas covered: This review offers an explanation of the mechanism of action and of the pharmacokinetics of sorafenib, and gives readers a complete overview of Phase I and II studies on the clinical efficacy, tolerability and safety of this agent in the setting of ovarian cancer (OC) treatment. Expert opinion: The available results from the studies which investigated the use of sorafenib for OC treatment demonstrated poor clinical benefit either as single agent or in combination therapy. The most promising results have been achieved combining sorafenib with bevacizumab, although overlapping and cumulative toxicities should be taken in consideration. Research should focus its attention to the development of reliable predictive biomarkers to assess response and direct therapy in order to allow patient selection and improving treatment schedules maximizing the clinical benefit and simultaneously minimizing the toxicity related to the chemotherapy. Further studies are needed to evaluate the role of sorafenib in the primary treatment of OC.

The potential of sunitinib as a therapy in ovarian cancer.

Introduction: Sunitinib malate (SU11248; Sutent®; Pfizer, Inc., New York) is a multi-kinase inhibitor currently approved for use in advanced renal cell carcinoma (RCC), imatinib-resistant/-intolerant gastrointestinal stromal tumours and progressive, well-differentiated pancreatic neuroendocrine tumours in patients with unresectable, locally advanced or metastatic disease. Areas covered: This article describes the mechanism of action and of the pharmacokinetics of sunitinib; further, it summarizes Phase I and II trials on the clinical efficacy, tolerability and safety of this agent in the setting of ovarian cancer (OC) treatment. Expert opinion: On the basis of the current literature, sunitinib has shown modest antitumour activity and acceptable toxicity. Studies investigating the impact of horizontal and vertical combinations should represent a priority of future research. Although clinical Phase II trials on the use of sunitinib in the treatment of OC demonstrated an acceptable profile of AEs, a greater comprehension of the toxicity of this compound is recommended.