Mario Valenzano Menada

Università degli Studi di Genova, Genova, Liguria, Italy

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Publications (39)88.93 Total impact

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    ABSTRACT: Introduction: Cervical cancer is still a major cause of morbidity and mortality in women. Early stages and locally advanced cervical cancer are currently treated respectively with surgery and chemoradiation with good prognosis. Persistent, recurrent and metastatic cervical cancers have a poor prognosis. Angiogenesis has been identified as a crucial factor for cervical cancer growth. Recently, research has increasingly focused on the development of targeted therapies, such as anti-angiogenic drugs. Amongst such drugs, bevacizumab, a recombinant humanized monoclonal antibody has been the subject of extensive investigation, including its use in cervical cancer. This was recently approved for the treatment of patients with metastatic, recurrent, or persistent cervical cancer. Areas covered: The aim of this review is to discuss the role of bevacizumab in both locally advanced and metastatic or recurrent cervical cancer and to analyze the studies that have led to the approval of bevacizumab in cervical cancer. Expert opinion: The use of bevacizumab in combination with other chemotherapies in cervical cancer has been proven safe and effective, with a significant improvement in overall survival of patients with advanced cervical cancer. Combination therapy using bevacizumab has been demonstrated to increase toxicity rates but it does not impair patient's quality of life.
    No preview · Article · Jan 2016 · Expert Opinion on Biological Therapy
  • S Bogliolo · P Marchiole · P Sala · E Giardina · G Villa · E Fulcheri · M Valenzano Menada
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    ABSTRACT: The pathologic status of lymph node represents the most important prognostic factor in vulvar cancer patients, but a complete groin dissection is associated with high post-operative morbidity. Sentinel lymph node (SLN) could be representative of the totality of regional lymph nodes and consequently its biopsy might have a significant impact on clinical management in vulvar cancer patients. From January 2006 to December 2010 45 patients with vulvar carcinoma are evaluated. Preoperative lymphatic mapping with technetium-99m-labeled nanocolloid was performed in all patients, followed by radioguided intraoperative detection. The detection rate is 100% of patients. All the SLNs were dissected separately for histopathological evaluation and a routine inguinofemoral lymphadenectomy was performed. Nine patients had positive SLNs. In the remaining 36 patients with negative SLNs, one of them showed positive non-SLNs at histological examination. It was the only false negative case in the present series. Based on literature review, lymphoscintigraphy and sentinel node biopsy under gamma-detecting probe guidance offer a reliable and careful method to identify sentinel node in early vulvar cancer. Taking certain guidelines, SLN biopsy seems to be a safe alternative to inguinofemoral node dissection in order to reduce morbidity of surgical treatment.
    No preview · Article · Apr 2015 · European journal of gynaecological oncology
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    S Ferrero · E Biscaldi · M Morotti · P L Venturini · V Remorgida · G A Rollandi · M Valenzano Menada

    Full-text · Dataset · Jun 2014
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    ABSTRACT: 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.
    Full-text · Article · Jun 2014 · International Journal of Gynecological Cancer
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    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.
    No preview · Article · Sep 2013 · Expert Opinion on Investigational Drugs
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    Matteo Morotti · Cm Becker · Mario Valenzano Menada · Simone Ferrero
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    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.
    Full-text · Article · Jul 2013 · Expert Opinion on Investigational Drugs
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    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.
    No preview · Article · May 2013 · Expert Opinion on Investigational Drugs
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    ABSTRACT: Background: Uterine myomas are the most common tumors of the female genital tract; they are mesenchymal tumors that arise from smooth-muscle cells and extracellular matrix of the uterus. They are less common in adolescents than in adults, and their clinical presentation is usually represented by abdominal/back pain, menstrual disorders, and vaginal bleeding. Case: The case report is described of a 14-year-old girl who presented to our Institution with the chief complaint of menstrual disorders (menorrhagia), and abdominal and back pain. The abdominal examination revealed a large mass extending 3 cm above the umbilical-transverse line. Abdominal ultrasound and magnetic resonance imaging (MRI) confirmed the presence of a mass that originated from the myometrium of the posterior uterine wall. The patient received an intramuscular injection of leuprolide acetate (3.75 mg, Decapeptyl, Ipsen, Rome, Italy) in order to reduce the volume of the mass before surgery and to decrease the intraoperative blood loss. Twenty-two (22) days after the first injection of leuprolide, the patient was admitted again to our Department because of fever and intense abdominal pain of increasing severity. Microscopic examination, immunohistochemical and the cytological examination of the fluid found in the pouch of Douglas during surgery confirmed the benign nature of the uterine mass, hypothesized through clinical and imaging examinations. Results: At 2-year follow-up, no recurrence of myoma was observed. Conclusions: Large uterine myomas may be diagnosed in adolescents. Before surgery, combining ultrasonography with MRI permits precise information to be obtained on the nature of the mass. Fertility sparing and low surgical injury are mandatory in this population.
    No preview · Article · Apr 2013 · Journal of Gynecologic Surgery
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    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.
    Full-text · Article · Mar 2013 · International Journal of Gynecological Cancer

  • No preview · Article · Oct 2012 · European Journal of Surgical Oncology
  • M Moioli · A Papadia · S Mammoliti · E Pacella · S Menoni · M V Menada · N Ragni
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    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.
    No preview · Article · Apr 2012 · Minerva ginecologica
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    Matteo Morotti · Mario Valenzano Menada · Pier Luigi Venturini · Simone Ferrero
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    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.
    Full-text · Article · Mar 2012 · Expert opinion on biological therapy
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    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.
    Full-text · Article · Feb 2012 · Gynecologic Oncology
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    M Morotti · M. Valenzano Menada · P L Venturini · S Mammoliti · S Ferrero
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    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.
    Full-text · Article · Feb 2012 · Expert Opinion on Investigational Drugs
  • P Sala · P Marchiolè · G Cittadini · M. Valenzano Menada · M Moioli · S Mammoliti · S Costantini
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    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.
    No preview · Article · Jan 2012 · European journal of gynaecological oncology
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    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.
    Full-text · Article · Dec 2011 · Archives of Gynecology
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    S Ferrero · E Biscaldi · M Morotti · P L Venturini · V Remorgida · G A Rollandi · M. Valenzano Menada
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    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.
    Full-text · Article · May 2011 · Ultrasound in Obstetrics and Gynecology
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    Matteo Morotti · Mario Valenzano Menada · Pier Luigi Venturini · Simone Ferrero
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    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.
    Full-text · Article · Mar 2011 · Expert Opinion on Drug Metabolism & Toxicology
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    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.
    No preview · Article · Dec 2010 · Melanoma research
  • M Morotti · S Ferrero · S Bogliolo · P L Venturini · V Remorgida · M Valenzano Menada
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    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.
    No preview · Article · Jun 2010 · Minerva ginecologica