Hysterosalpingography in infertility investigation protocol: is it still useful?

PURPOSE OF INVESTIGATION: to assess the radiological findings of women undergoing hysterosalpingography (HSG) as initial infertility investigation protocol. MATERIALS AND METHODS: A retrospective study on infertile women who underwent HSG at Institute of Radiology of Sassari University, Italy. RESULTS: The present case series included 2,845 HSG, performed from January 1997 to March 2014. The age of the patients ranged from 20 to 48 years. The negative exams (tubal patency) were 2,039 out of 2,845 (71.67%). CONCLUSION: A technique of diagnostic imaging for the evaluation of infertility should be non-invasive, not expensive, rapid, of simple execution, and also be able to provide information on tubal patency and pelvic diseases. For these reasons, HSG today remains a useful diagnostic investigation tool in the diagnostic work-up of infertile patients.

Management of breast lobular carcinoma in situ: radio-pathological correlation, clinical implications, and follow-up.

PURPOSE OF INVESTIGATION: To show management of patients with breast lobular carcinoma in situ (LCIS). MATERIALS AND METHODS: This study is the retrospective review of 65 patients, between 1996 and 2012, with isolated LCIS of the breast, evaluated through clinical examination, ultrasound, and mammography at the first examination and follow-up. RESULTS: In 53 patients (81.54%), clinical examination was negative. In 14/65 (21.54%) cases, ultrasound was positive and led to biopsy. The clusters of tiny calcifications were the predominant mammographic pattern (45 cases, 69.23%). Forty-six patients (70.77%) underwent surgical biopsy after guided stereotactic placement of metallic marker (hook-wire), 12 (18.46%) by stereotactic vacuum biopsy (SVB), 5 (7.69%) by core needle biopsy (CNB) under ultrasound guidance, two (3.08%) patients CNB with clinically palpable nodules. Fourteen (21.54%) women underwent a quadrantectomy or total mastectomy after the first diagnosis; in this latter group follow-up was negative. Among the 51 patients (78.46%) who did not undergo quadrantectomy or total mastectomy, five relapses occurred, respectively, three LCIS and two infiltrating ductal carcinomas (IDC). Follow-up ranged from 12 to 144 months. CONCLUSION: LCIS is a risk factor for invasive carcinoma and should be managed with careful follow-up, but if there is a discrepancy between pathology and imaging, surgical excision is mandatory.

Immunohistochemical evaluation of epithelial antigen Ber-Ep4 and CD10: new markers for endometriosis?

BACKGROUND: Early and certain diagnoses of endometriosis are mandatory to begin the correct treatment and to exclude the risk of endometriosis-associated ovarian carcinoma (EOC) and endometrial stromal sarcoma (ESS). PURPOSE OF THE STUDY: To assess the immunohistochemical expression of Ber-Ep4, an epithelial antigen, and CD10 in endometriosis. MATERIALS AND METHODS: Forty-eight women underwent laparoscopic surgery for endometriosis and endometriotic samples were recovered for histology. In all surgical specimens Ber-Ep4 and CD10 were searched by an immnohistochemical method. The authors evaluated the correlations among the immunohistochemical positivity and the location of endometriosis. RESULTS: Most cases (40/48 83.34%) were represented by ovarian endometriotic cyst. Among the eight remaining cases, three (3/48, 6.25%) were pelvic endometriotic lesions, two (2/48, 4.17%) peritoneum of vesico-uterine pouch, one vaginal lesion (2.08%), one salpinx lesion (2.08%), and one inguinal location (2.08%). Ber-Ep4 and CD10 were expressed in 90% and in 100% of the ovarian lesions, respectively. In pelvic lesions Ber-Ep4 and CD10 showed both 66.67% of positivity and had the same pattern in peritoneal, salpinx, vaginal, and inguinal lesions (50%, 100%, 100%, 100%, respectively). Ber-Ep4 was negative in 6/48 (12.5%) cases whereas CDO10 was negative in 2/48 (4.17%) cases of endometriosis. The sensitivity of Ber-Ep4 and CD10 for endometriosis diagnosis were 87.50% and 95.83%, respectively. Immunohistochemistry for Ber-Ep4 showed positivity in all cases of endometriosis with typical cubic epithelium, whereas CD10 was positive in 1/2 (50%) atypical case. CONCLUSION: Immunohistochemical expression of Ber-Ep4 and CD10 was positive in most cases of endometriosis and was useful in differential diagnosis with mesothelial cysts. Ber-Ep4 was negative in cases of hyperplastic epithelium or cytological atypia; these cases are not well-differentiated and could be optimally treated by surgery and not by hormonal therapy because of the risk of cancer degeneration.

P16 immunostaining and HPV testing in histological specimens from the uterine cervix.

BACKGROUND: The cellular tumor suppressor protein pl61NK4a (p16) has been identified as a biomarker for transforming human papilloma virus (HPV) infections. P16 is a cyclin-dependent kinase inhibitor that regulates the cell cycle and cell proliferation by inhibiting cell cycle G1 progression. PURPOSE OF THE STUDY: To confirm the role of p16 as biomarker for transforming HPV infections and possible clinical applications in histological samples from the uterine cervix. MATERIALS AND METHODS: The subject of this study included 56 biopsies of the cervical canal collected from January 2012 to September 2012 in the Institute of Pathology of the University of Sassari. The search for HPV immunohistochemistry was performed with the monoclonal antibody DAKO 1:25, while for the detection of p16 was used CINtecTM p16 (INK4a) histology kit. RESULTS: In 56 biopsies performed in women aged between 23 and 69 years, the authors highlighted, by histological analysis, 24 cases of low-grade squamous intraepithelial lesion (LSIL) - cervical intraepithelial neoplasia (CIN1) and 31 cases of high-grade squamous intraepithelial lesion (HSIL) - CIN2/3); 15 CIN2, 14 CIN3, and two cervical squamous cell carcinoma in situ (SCIS). One case was an infiltrating squamous cell carcinoma (ISC). In 24 CIN1, there was a 16.67% positivity for p16 and an equal percentage occurred for HPV. In 15 cases of CIN2 the percentage of positivity for p16 was considerably increased (73.33%), unlike the search for HPV which had a positivity rate of 20%. Finally, in 14 cases of CIN3, and in three carcinomas, the positivity for p16 was equal to 100%, however the search for HPV positivity was between 0% and 7.14%. CONCLUSIONS: These results demonstrated that p16 was a highly sensitive marker of cervical dysplasia. The authors have shown that p16 overexpression increased with the severity of cytological abnormalities and that had a greater ability to identify the viral infection compared to the classical immunohistochemical staining for HPV.

Cisplatin-gemcitabine as palliative chemotherapy in advanced squamous vulvar carcinoma: report of two cases.

Vulvar cancer (VC) is a rare disease, usually diagnosed in a stage still amenable to potentially curative treatments, including surgery and/or radiation therapy with or without chemotherapy. Several patients however present at diagnosis with metastatic disease and another 30-50% will relapse. Prognosis of metastatic or recurrent disease not amenable to salvage surgery or radiotherapy is very poor. Evidence about the efficacy of chemotherapy in this setting is limited and its role still remains unclear. At present there is no standard treatment for advanced VC and patients are usually treated with schedules adopted for chemoradiation or extrapolated from cervical cancer. We report our experience using a cisplatin-gemcitabine regimen in two cases of metastatic squamous cell VC. No response was obtained with this schedule. No other data are available in the literature about the choice of a cisplatin-gemcitabine regimen in this patient subset. The paucity of evidence about the role of palliative chemotherapy in metastatic VC justifies any effort to implement knowledge. For this reason we think it is notable to also report a negative experience. It is not possible for us to conclude that this chemotherapy would be unable to provide any benefit in a larger sample of patients; nonetheless we think that new agents, rather than combinations of older drugs, could hopefully provide more benefit.

Immunohistochemical evaluation of a new epithelial antigen, BER-EP4 in ovarian cancer: a propos of 62 cases.

OBJECTIVE: To assess the immunohistochemical expression of BerEP4, a new epithelial antigen in ovarian cancer. METHODS: We studied 62 cases of ovarian cancer in which BerEP4, CEA and CA-125 were investigated by an immunohistochemical method. We evaluated the correlations among immunohistochemical positivity and the grading, histotype and stage of disease. RESULTS: BerEP4 was positive in 45 out of 62 cases (72.58%), CA-125 in 36 out of 62 cases (58.06%) and CEA in ten out of 62 cases (16.13%). BerEP4 was present both in serous and in mucinous tumors (80.96% vs. 80.77%). CA-125 was mainly expressed in serous vs mucinous tumors (66.67% vs. 57.69%). CEA was more prevalent in mucinous vs. serous tumors. Ber-EP4 was mainly expressed in G1 (75%) and G2 (77.27%). CA-125 was more present in G1 and G3 (both 62.50%) than G2 (50%), whereas CEA showed positivity in G1: 12.50%, G2: 22.73% and G3: 12.50%. There were no differences among the three antigens studied with regard to clinical stage. CONCLUSIONS: In our study Ber-EP4 was positive in 45 out of 62 cases (72.58%) of primary epithelial ovarian cancers. The presence of this antigen seemed to be related to the histotype and grading but not to clinical stage.

Analysis of epidermal growth factor receptor (EGFR) status in endometrial stromal sarcoma.

PURPOSE: Endometrial stromal sarcomas (ESSs) are rare neoplasms, which are currently treated by surgery, whereas effective adjuvant therapies have not yet been established. Recently, epidermal growth factor receptor (EGFR) expression has been described in ESS, and a potential role of EGFR-targeted adjuvant therapies has been proposed. The aim of this study was to analyze EGFR status in an ESS series and to evaluate their potential role as molecular targets. MATERIALS AND METHODS: EGFR status was investigated in a total of ten cases of ESS, which included seven low-grade ESS and three undifferentiated ESS cases. EGFR expression levels were assessed by immunohistochemistry, and gene amplification analysis was performed with dual-color fluorescence in situ hybridization (FISH). RESULTS: Nine out of ten ESS cases showed positive immunostaining, whereas FISH analysis demonstrated constantly negative results. CONCLUSIONS: This study confirmed that EGFR is frequently overexpressed in ESS. FISH analysis did not show EGFR amplification in any of the tumors, therefore EGFR expression in ESS should be related to different genetic mechanisms.

CT-guided cryoablation of both breast cancer and lymph node axillary metastasis.

Breast conservation is a major goal of cancer treatment. Many different minimally invasive options have been considered such as cryoablation. This technique is the best visualized of all ablation techniques due to the phase change during ice formation. We describe a case of breast cancer with lymph node axillary metastasis treated by CT-guided cryoablation. Cryoablation may have unique benefits for cost-effective outpatient breast cancer therapy using only local anesthesia and/or mild sedation.

Receptor modifications in vulvar dystrophies before and after treatment with topical hormones: comparison between the dextran-charcoal technique and immunohistochemical evaluation.

PURPOSE OF INVESTIGATION: The objective of the study was first to quantify estrogen receptors (ERs) and progesterone receptors (PRs) in dystrophic vulvar tissue before and after topical hormone treatment in an attempt to evaluate whether receptor modifications occurred. Second we compared quantitative analysis with immunohistochemical staining of the vulvar specimens. METHODS: We studied 115 vulvar specimens obtained from 75 consenting women ranging from 21 to 78 years of age. Of the patients, 12 had histologically normal vulvar skin, 45 had vulvar dystrophies that were not treated by topical steroid therapy, 28 patients had vulvar dystrophies that were treated by testosterone propionate (TP) 2%, 12 patients had vulvar dystrophies that were treated by progesterone in hydroalcoholic gel and 18 patients had vulvar malignant tumors. For immunohistochemical analysis we considered 25 cases of vulvar dystrophies: 11 cases of squamous hyperplasia (SH) and 14 cases of lichen sclerosus (LS). Among these 25 cases, 15 (5 SH and 10 LS) were treated with TP 2%. RESULTS: After treatment of the vulvar dystrophies with progesterone, the positivity of ERs decreased (58.3% vs 77.8%). After treatment of the vulvar dystrophies with TP 2%, the positivity of PRs significantly decreased (14.3% vs 68.9%) whereas after treatment with progesterone the positivity of PRs increased (83.3%). The immunohistochemical study showed some differences in comparison to the quantitative study. In fact we found low basal positivity especially for PRs (16% vs 68.9% of the quantitative study). This finding was due to the use of a cutoff of at least ++ in order to increase the specificity. After treatment with TP 2%, we observed an increase of immunohistochemical positivity for ERs even in cases that were negative before treatment and a lack of PRs even in cases that were positive before treatment. CONCLUSIONS: These data demonstrate the efficacy of androgen therapy with TP 2% in vulvar dystrophies with increased trophism due to the increase of ERs.

Epidemiological aspects of ovarian malignancies in North Sardinia in the period 1992-2001.

Malignant ovarian tumors have been continuously increasing in Western countries and represent the leading cause of death for gynecological cancer. In fact, the mortality for malignant ovarian tumors remains very high with a low percentage of 5-year survival in the advanced stage of disease. The aim of this study was to evaluate the incidence trend and epidemiological characteristics of malignant ovarian tumors in the Province of Sassari, Sardinia (Italy) in the period 1992-2001 and to report the variations in comparison to the 1974-1985 period. The analysis of our data regarding the period 1992-2001, if compared with those of the period 1974-85, showed an increase of malignant ovarian tumors which triplicated achieving an incidence of 11.99/100,000 vs 4.27/100,000. The analysis of our epidemiologic data showed an increase of the age of first diagnosis (mean 60.9 years for epithelial ovarian tumors), the occurrence of the cancer in women at low socio-economic levels and a family history of cancer among the patients with malignant ovarian tumors. These data suggest that both local environmental factors combined with genetic characteristics play a role in the pathogenesis of ovarian tumors. The genetic characteristics could be of particular interest because Sardinia has been through the centuries a geographical area with little population migration. The marked increase in the incidence of ovarian tumors in the last several years points out the need to organize systematic screening by ultrasonography in our population.

Epidemiology of malignant breast tumors in the province of Sassari (Sardinia, Italy) in the period 1992-2002.

The aim of this study was to evaluate the incidence of malignant breast tumors in the Province of Sassari, Sardinia (Italy) in the period 1992-2002 and to report the variations in comparison to the 1974-1985 period. The analysis of our data showed that the overall number of malignant breast tumors was more than doubled from 1,139 cases in the period 1974-1985 to the 2,735 cases in the period 1992-2002, and the mean rate/100,000 changed from 43.4 to 106.0. The incidence in the age classes 45-64 years, which were at enhanced risk for breast cancer, was globally increased, changing from 143.6/100,000 to 198.7/100,000. On the other hand, the incidence in the youngest age classes (30-34 yrs) was reduced from 59.5% to 27.0%. The analysis of the histotypes showed a relative reduction of ductal carcinoma in the period 1992-2002 in comparison to the previous period 1974-1985 (65.2% vs 82.0%) whereas the incidence of anaplastic forms increased in advanced ages of life. We reported an important reduction of T0 tumors from 3.4% to 0.1%. These data could be due to the low diffusion of screening programs in Sardinia. Tumor metastases were more frequent in advanced age classes. In conclusion, the worrying data of the strong reduction of T0 cases, the increased age of first diagnosis and the advanced forms with positive nodal metastases showed that the prevention program has not been yet well organized.

Placental and fetal pulsatility indices in gestational diabetes mellitus.

OBJECTIVE: To assess the usefulness of placental and fetal Doppler velocimetry in the surveillance of gestational diabetes mellitus (GDM). STUDY DESIGN: We studied 89 patients with GDM. All fetuses underwent umbilical, fetal descending thoracic aorta and fetal middle cerebral artery pulsatility index (PI) assessment. Doppler results were not used for management. We correlated PI with route of delivery and with the following perinatal complications: small size for gestational age, cesarean section (CS) for acute fetal distress (AFD), respiratory distress syndrome, hyperbilirubinemia, hypocalcemia, hypoglycemia, macrosomia and stay in a neonatal intensive care unit. RESULTS: Seventy-seven patients (87%) had normal Doppler measurements, while 12 (13%) showed one or more abnormal measurements. The greatest incidence of CS for AFD (42% vs. 16%, P < .001), as well as neonatal hyperbilirubinemia (25% vs. 10%, P < .001) and hypoglycemia (25% vs. 5%, P < .001) was reported among the women with abnormal Doppler measurements. CONCLUSION: Fetal placental hemodynamics are normal in most cases of GDM. In a small percentage of cases we observed abnormal fetal placental PI associated with a higher incidence of perinatal complications. Hence, the finding of abnormal PI must induce the physician to carry out more intensive obstetric care of women with GDM.

Endometrial carcinoma in the Sardinian population.

The biological and clinical characteristics of endometrial carcinoma in Sardinia were examined, with particular regard to the very high incidence (42.7/100,000 age-selected women) of this neoplasia in this Island. The use of post-surgical Radiotherapy on the basis of the protocols of integrated therapies allowed us to reduce the incidence of relapses in these last few years, with an evident increase in survival.

Non-Hodgkin lymphoma: a rare primary vulvar localization.

Malignant lymphomas concern the female genital tract in 30% of cases. The majority (more than 90%) are non-Hodgkin lymphoma, involving in order of frequency, ovary (49%), uterus (29%), Fallopian tubes (11%), vagina (7%), vulva (4%). So a primary vulvar localization seems to be quite unusual; in fact only 5 cases have been reported since 1937 up to now. We report a case of vulvar non-Hodgkin lymphoma we observed in our Institute.

The treatment of cervical carcinoma in the Sardinian population.

The epidemiological and clinical characteristics of cervical carcinoma in Sardinia were examined, with particular regard to the low incidence (6.47/100,000 women) of these neoplasias. Postsurgical adjuvant Radiotherapy in the high-risk cases has allowed a constant improvement in therapeutic results, with a low relapse-incidence and a high percentage of survival, especially in first and second stage treated cases.

Our experience regarding precautional chemotherapy in breast cancer.

14 patient with breast cancer of loco regional diffusion (M0), 4 of whom had negative axillary lymph nodes, were administered precautional chemotherapy with CMF, on the basis of anatomo-clinical prognostic elements (size of the neoplasia, grading (tumoral limits, neoplastic embolisation etc.). Such elements with data on hormonal receptors allowed us to select the patients with high relapse risk, to undergo medical treatment.

The management of cervical carcinoma in the Gynaecologic and Obstetric Institute of Sassari in ten-year period 1980-89.

We have considered 91 cases of uterine cervical carcinoma observed in the period 1980-89, of which 31 (34%) at stage 0, and 23 (25.2%) at stage IB. The operative index was of 85.7%. Of 78 cases operated, 22 (28.2%) were treated with post-surgical adjuvant radiotherapy because of the presence of risk factors. The relapse incidence (follow-up 8-118 months) was in total 14.6% (12 relapses) with an NED-survival of 79.1% (at the first stage B 4.3% of relapses with an NED-survival of 95.6%). We have emphasized the importance of adjuvant radiotherapy which has allowed the progressive improvement in the therapeutic results of the last years.

Female genital cancer incidence in the Province of Sassari from 1974 to 1983.

The incidence of gynaecologic tumours in the Province of Sassari has been studied in order to estimate their value and to make a comparison with the ones industrialised countries. The global incidence of uterine cancer (corpus uteri plus cervix) is of 18.16/100,000 women; 11.99/100,000 for cancers of corpus uteri and 6.17/100,000 for cervical carcinoma including in situ forms. The incidence of gynaecologic tumors for the District of Sassari is equivalent to that reported in Western countries and it does confirm indeed a constant and progressive increase in tumours of the corpus uteri and a reduction in cervical carcinoma especially if in situ forms are excluded.

The modifications of T-lymphocyte cell subpopulations in patients with beta-interferon intracavitary treatment.

18 patients with malignant genital or mammary neoplasia, treated with endocavitary Beta-Interferon (intrapleural or intraperitoneal), were examined in order to study the modifications of T-lymphocyte subpopulations (T3, T4, T8, T4/T8) in the peripheric blood. An improvement in the immune state in complessively 50% of the patients treated was observed, while there were no modifications in the remaining patients (in 3 patients with advanced ovarian cancer there was persistence of immunodepression preexisting to treatment). This indicates that endocavitary Beta-Interferon induced very poor immune response at peripheric level (contrary to what other Authors have described at peritoneal level), correlated to the dose used and to the extent of serous surface exposed to the drug.

The treatment of endometrial carcinoma: our experience in the period 1983-89.

The Authors evaluated 87 cases of endometrial carcinoma, of whom 65 (74.7%) at pathological stage I. The surgical ratio was (96.5% 84/87 cases), and 31 cases were subjected to adjuvant postsurgical Radiotherapy because of the presence of risk factors. The incidence of relapses resulted complessively in 14.2%, with a NED-survival of 86.1% and an overall survival of 91.9% at the pathological stage I. The Authors emphasise particularly the importance of post-surgical Radiotherapy in the cases at risk, which allowed an important decrease of the incidence of relapses at stage I with regard to previous studies.