[Show abstract][Hide abstract] ABSTRACT: 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.
International Journal of Gynecological Cancer 06/2014; · 1.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Expert Opinion on Investigational Drugs 09/2013; · 4.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Expert Opinion on Investigational Drugs 07/2013; · 4.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Expert Opinion on Investigational Drugs 05/2013; · 4.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
International Journal of Gynecological Cancer 03/2013; · 1.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Neoadjuvant chemotherapy represents a promising alternative to concomitant chemo-radiation therapy in locally advanced cervical cancer patients. The aim of this study was the evaluation of pathologic response rates, toxicity and predictors of response in locally advanced cervical cancer patients treated with neoadjuvant cisplatin and paclitaxel followed by radical surgery.
Fourteen patients with stage IB2 to IIB cervical cancer received three cycles of cisplatin 75 mg/m2 and paclitaxel 175 mg/m2 intravenously every three weeks followed by radical hysterectomy and bilateral pelvic lymphadenectomy. Toxicity, pathologic response and predictors of response were evaluated.
Chemotherapy related toxicities we-re as follows: alopecia 100%, asthenia 35.7%; nausea and vomiting 14.3%; paclitaxel hypersensitivity 7.1%, neutropenia 7.1%. Optimal, partial and no pathologic response was achieved in 21.4%, 64.3% and 14.2% of the patients, respectively. Based on lack of pathologic risk factors, 43% of the patients did not receive any adjuvant radiotherapy. Better response rates were obtained in patients with stage IIB, tumor diameter <5 cm, Hb >12 g/dL and SCC antigen <1.5 mg/dL. None of these variables reached statistical significance.
Neoadjuvant chemotherapy with cisplatin and paclitaxel in locally advanced cervical cancer appeared to be well-tolerated. Even though the TIP regimen has been shown to be more effective than the TP regimen in randomized controlled prospective trial, the TP regimen remains a reasonable alternative in those patients in whom the TIP regimen is considered or shown to be too toxic.
[Show abstract][Hide abstract] ABSTRACT: INTRODUCTION: There is a critical need to develop effective new strategies for the management of patients with advanced or recurrent endometrial cancer (EC) and molecular targeted therapies; in particular, antiangiogenic drugs represent an interesting field of pharmacological research. One of the most interesting of these agents is bevacizumab, a monoclonal antivascular endothelial growth factor antibody. AREAS COVERED: Mechanism of action and clinical trials of bevacizumab in EC, and suggestions for its future use are reviewed. The most relevant papers and the meeting abstracts published up to December 2011 were used as sources for this review. The purposes of this manuscript are to discuss the rationale of interfering with the process of tumor angiogenesis in EC, to help readers in understanding the mechanism of action of bevacizumab, and to provide a comprehensive summary of initial preclinical and clinical results of this drug in EC patients. EXPERT OPINION: Recent advances in the understanding of the molecular biology of EC have led to development of targeted therapies. Among these, antiangiogenic agents are one of the most promising therapies.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: INTRODUCTION: Current therapies for recurrent ovarian cancer (OC) yield relatively modest improvements in survival. Many drugs are available but recently a renewed interest is addressed on antimetabolite drugs. Pemetrexed (PEM) is a multitargeted antifolate cytotoxic agent mainly used in lung cancer. AREAS COVERED: This review summarizes the available evidence on the use of PEM in the treatment of OC. This article consists of material obtained via Medline, PubMed and EMBASE literature searches, up to November 2011. Currently available published data on mechanism of action, pharmacokinetics, safety and efficacy of PEM in the treatment of recurrent OC are described. EXPERT OPINION: Eight trials evaluated the use of PEM in OC patients. Studies using PEM in combination with carboplatin in platinum-sensitive OC suggested that the response rate is similar to other combination therapies. However, based on the absence of randomized trials comparing this doublet with currently used combination treatments, it is difficult to draw conclusions on the efficacy of PEM regimens in these patients. In platinum-resistant OC patients, two studies suggested that PEM alone might have equivalent activity to other single-agent treatment. Further pharmacogenomic and clinical data are warranted to better define the role of PEM in the treatment of recurrent OC.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the accuracy of magnetic resonance imaging (MRI) in staging cervical tumors after neoadjuvant chemotherapy (NACT).
26 women, affected by locally advanced cervical cancer and triaged for surgery after NACT, were submitted to three cycles of neoadjuvant chemotherapy. All patients were submitted to MRI before and after NACT. We evaluated the MRI sensitivity and specificity in staging cervical tumors after chemotherapy, relating MRI findings after NACT with the pathological findings as the gold standard.
In our series, MRI sensitivity was 58.8% and specificity was 66.7%.
In our study MRI accuracy after NACT was lower than that of MRI used to stage patients with early cervical cancer scheduled for primary surgery, reported by the literature. MRI false negative cases are the major problem because of the delay in application of an effective therapy in non responders to NACT.
European journal of gynaecological oncology 01/2012; 33(1):31-6. · 0.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the available information on the preoperative diagnosis of borderline ovarian tumors (BOTs).
Articles were identified through electronic databases (Medline and EMBASE, MEDLINE, PubMed), no date or language restrictions were placed; relevant citations were hand searched.
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.
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.
Archives of Gynecology 12/2011; 285(4):1103-12. · 0.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: INTRODUCTION: Safe and effective treatments are needed for ovarian cancer. While there are many drugs currently available, there has recently been a renewed novel interest in the use of anthracyclines. AREAS COVERED: This review summarizes the available evidence on pharmacokinetic (PK) and toxicology implications of anthracyclines and pegylated liposomal doxorubicin (PLD) in the clinical management of women with epithelial ovarian cancer. This article consists of material obtained via Medline, PubMed and EMBASE literature searches, up to September 2010. EXPERT OPINION: PLD is a liposomal formulation of doxorubicin (DXR), with a distinct pharmacokinetic profile, characterized by extended circulation time and a reduced clearance and volume of distribution with respect to the free drug. PLD is effective and well tolerated in relapsed ovarian cancer. The toxicity profile of PLD is characterized by dose-limiting mucosal and cutaneous toxicities, mild myelosuppression and decreased cardiotoxicity compared to free DXR. The good response rate, toxicity profile and pharmacokinetic profile of PLD suggest that PLD could be an option in first-line and second-line treatment in ovarian cancer; especially in those who had experienced taxane-induced toxicity or had a poor performance status.
Expert Opinion on Drug Metabolism & Toxicology 03/2011; 7(6):707-20. · 2.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To compare the accuracy of multidetector computerized tomography enteroclysis (MDCT-e) and rectal water contrast transvaginal ultrasonography (RWC-TVS) in determining the presence and extent of bowel endometriosis.
This prospective study included 96 patients of reproductive age with suspicion of bowel endometriosis. Patients underwent MDCT-e and RWC-TVS before operative laparoscopy. Findings of MDCT-e and RWC-TVS were compared with histological results. The severity of pain experienced during MDCT-e and RWC-TVS was measured by a 10-cm visual analog scale.
Fifty-one patients had bowel endometriotic nodules at surgery. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy for the diagnosis of rectosigmoid endometriosis were 95.8% (46/48), 100.0% (48/48), 100.0% (46/46), 96.0% (48/50) and 97.9% (94/96) for MDCT-e and 93.8% (45/48), 97.9% (47/48), 97.8% (45/46), 94.0% (47/50) and 95.8% (92/96) for RWC-TVS. MDCT-e was associated with more intense pain than was RWC-TVS.
MDCT-e and RWC-TVS have similar accuracy in the diagnosis of rectosigmoid endometriosis, but patients tolerate RWC-TVS better than they do MDCT-e.
Ultrasound in Obstetrics and Gynecology 02/2011; 37(5):603-13. · 3.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Melanoma research 12/2010; 20(6):443-9. · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The rectosigmoid is the most frequent location of intestinal endometriosis. Although several techniques have been proposed for the diagnosis of intestinal endometriosis, no gold standard is currently available. In this review, we describe in details a new technique for the diagnosis of rectosigmoid endometriosis: rectal water-contrast transvaginal ultrasonography.
During transvaginal ultrasonography, an assistant inserts a 6-mm flexible catheter through the anal os into the rectal lumen; the insertion of this catheter is evaluated under ultrasonographic control. Water contrast is instilled slowly in the rectum to permit intestinal distension. The colonic wall evaluation is obtained by positioning the transvaginal probe against a length of the sigmoid colon to obtain either axial or longitudinal images. The injection of the saline solution facilitates the identification of recto-sigmoid endometriotic nodules which appear as rounded or triangular hypoechoic masses, located anterior or lateral to the bowel.
This technique has high sensitivity and specificity in the diagnosis of rectal infiltration in women with rectovaginal endometriosis. The distance between the nodules and the mucosal layer permits to estimate the depth of infiltration of these endometriotic lesions within the intestinal wall. Rectal distensibility can be estimated. The procedure is well tolerated by the patients.
Water distension of the rectum facilitates the identification of intestinal endometriosis during transvaginal ultrasonography.
[Show abstract][Hide abstract] ABSTRACT: Metastatic 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.
An 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.
Genital 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.
Archives of Gynecology 10/2009; 281(4):769-73. · 0.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: According to current definition, peripartum cardiomyopathy (PPCM) is a rare disorder in which left ventricular dysfunction and symptoms of heart failure occur in the last month of pregnancy. It has been reported that the incidence of PPCM is 1 in 3,000-4,000 live births. The pathogenesis is poorly understood, however, infectious, immunologic, and nutritional causes have been hypothesized. Clinical presentation includes usual signs and symptoms of heart failure, and unusual presentations such as thromboembolism. Diagnosis is based upon the clinical presentation of congestive heart failure and the objective evidence of left ventricular systolic dysfunction. Early diagnosis and initiation of treatment are essential to optimize pregnancy outcome. Patients with systolic dysfunction during pregnancy are treated similar to patients who are not pregnant. The mainstays of medical therapy are digoxin, loop diuretics, sodium restriction and afterload reducing agents (hydralazine and nitrates). Due to a high risk for venous and arterial thrombosis, anticoagulation with subcutaneous heparin should be instituted. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers should be avoided during pregnancy because of severe adverse neonatal effects. Effective treatment reduces mortality rates and increases the number of women who fully recover left ventricular systolic function. The prognosis is poor in patients with persistent cardiomyopathy. Subsequent pregnancies are often associated with recurrence of left ventricular systolic dysfunction.
Archives of Gynecology 09/2009; 281(2):183-8. · 0.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
The Journal of reproductive medicine 07/2009; 54(6):366-72. · 0.75 Impact Factor