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Purpose The noninterventional, prospective NIMES‐ROC phase IV study (NCT02825420) evaluated trabectedin plus pegylated liposomal doxorubicin (PLD) in real‐life clinical practice. Patients and Methods Eligible participants included adults with platinum‐sensitive recurrent ovarian cancer (PS‐ROC) who had received one or more cycles of trabectedin/PLD before inclusion according to the marketing authorization. The primary endpoint was progression‐free survival (PFS) according to investigator criteria. Results Two hundred eighteen patients from five European countries were evaluated, 72.5% of whom were pretreated with at least two prior chemotherapy lines and received a median of six cycles of trabectedin/PLD (range: 1–24). Median PFS was 9.46 months (95% confidence interval [CI], 7.9–10.9), and median overall survival (OS) was 23.56 months (95% CI, 18.1–34.1). Patients not pretreated with an antiangiogenic drug obtained larger median PFS (p < .007) and OS (p < .048), largely owning to differences between the two populations. Twenty‐four patients (11.0%) had a complete response, and 57 patients (26.1%) achieved a partial response for an objective response rate (ORR) of 37.2%. Fifty‐nine patients (27.1%) had disease stabilization for a disease control rate of 64.2%. No statistically significant difference in PFS, OS, or ORR was observed by BRCA1/2 status and platinum sensitivity. Most common grade 3/4 adverse events (AEs) were neutropenia (30.3%), anemia (6.4%), thrombocytopenia (5.5%), and asthenia (5.0%). No deaths attributed to treatment‐related AEs or unexpected AEs occurred. Conclusion The combination of trabectedin/PLD represents a clinically meaningful and safe option for patients with PS‐ROC regardless of prior treatment with an antiangiogenic drug, being comparable with previously observed outcomes in selected and less pretreated patients from clinical trials. Implications for Practice This noninterventional, prospective study, conducted in 57 reference sites across Europe, consistently confirmed that trabectedin plus pegylated liposomal doxorubicin (PLD) in routine clinical practice represents a clinically meaningful and safe option for women with platinum‐sensitive recurrent ovarian cancer. Although the study population represented a heterogeneous, older, and more pretreated population than those in prospective clinical trials, the combination of trabectedin plus PLD induced comparable clinical benefits, with a similar and manageable safety profile. Overall, these findings show that trabectedin in combination with PLD maintains antitumor activity when administered to heavily pretreated patients in real‐life clinical practice., This clinical trial evaluated the use of trabectedin plus pegylated liposomal doxorubicin (PLD) in patients with platinum‐sensitive recurrent ovarian cancer and its efficacy and safety in routine clinical practice in five European countries.

Background/aim We evaluated the efficacy of neoadjuvant chemotherapy (NACT) in reducing locally-advanced breast cancer (LABC) size, thus improving breast-conserving surgery (BCS) rates, as well as its long-term outcome. Patients and methods We analyzed 59 patients treated between 1999-2017 with NACT and subsequent surgery for LABC. Results We observed a tumor size reduction in 95% of cases, resulting in downstaging in 62.7%. The average tumor shrinkage was 49%. Women with a reduction in tumor size >50% after NACT had better 10-year OS rates than women with a reduction ≤50% (p=0.025). NACT allowed to perform BCS in 44% cases, whereas the remaining 56% cases underwent mastectomy. Overall, we observed recurrences in 37.2% patients. Recurrence rates after BCS and mastectomy were 30.7% (6 loco-regional and 2 distant cases) and 42.4% (5 loco-regional and 9 distant cases), respectively (p=0.07). Conclusion NACT confirmed its effectiveness in reducing mastectomy rates by approximately 50%, without increasing the risk of local or distant recurrences.

Background Implant-based breast reconstruction after nipple-sparing mastectomy has been the most common breast reconstruction procedure performed, for both breast cancer treatment and prophylactically. Subpectoral implant placement with partial detachment of the pectoralis major muscle has been the procedure of choice for staged reconstruction and direct-to-implantation. Prepectoral implant placement has recently increased in popularity among plastic surgeons owing to the high rates of animation deformity, loss of muscle function, and chronic pain observed with submuscular implant placement. Acellular dermal matrices or synthetic meshes have been used for implant coverage and support to avoid capsular contracture and implant visibility. In the present study, we have introduced breast reconstruction actualized in nipple-sparing mastectomy and direct-to-implant with prepectoral polyurethane positioning (BRAND4P). Patients and Methods A total of 34 nipple-sparing mastectomies and immediate direct-to-implant breast reconstructions with prepectoral polyurethane-coated implant placement were performed in 21 patients (13 bilateral and 8 unilateral). The implant was placed subcutaneously in the exact place of the excised breast parenchyma with no further coverage. Results After a mean follow-up of 4 months, no major complications had been observed. No patient presented with animation deformity or grade III-IV capsular contracture. Patient satisfaction, assessed using the BREAST-Q, was excellent. Conclusions The BRAND4P method represents a novel prepectoral approach and a feasible alternative to subpectoral implant placement among the available implant-based breast reconstruction techniques.

Although NAC has been shown to be very effective in down staging of the axillary cavity and a complete pathological response (pCR) has been observed in 40-70% of cases (above all in triple negative and Her2+ patients), it was assumed that a pathological response of the tumor alter axillary lymphatic rainage for lymphatic canal fibrosis with cellular debris, reducing the probability of sentinel node (SLN) idetification, with a likely increase in the percentage of false negatives rate (FNR), which as shown by SENTINA trial, where it stands at values of 16%, with a detection rate (DR) of 80%. In light of these observations, different surgical strategies have been put in place to reduce the FNR rate, in order to imporve the number of sentinel/parasentinel nodes and the identification rate (IR) during SNLB in c N+ yc N0 patients, such as the use of double tracer (like vital dye or superparamagnetic iron oxide- SPIO, in association with Tc99), the clip placement in nodes involved before NAC and intraoperative ultrasound (IOUS). Here we will report our experience about the detection rate (DR) and the feasibility of the double tracers, SPIO (Magtrace) + Tc99. We enrolled 20 patients with diagnosis of invasive breast cancer with axillary metastasis, undergoing neodjuvant chemiotherapy and in axillary response after this (cN+ycN0). The overall lymph nodes removed were n°64 between sentinel and parasentinel nodes (52 with Magtrace and 29 with technetium, p-value 0.05). In 12/20 patients (60% of cases) the complementary use of Magtrace allowed us to reach a number of identified lymph nodes ≥ 3, avoinding axillary node dissection in 15/20 (75% of all patients). As demonstrated by our experience, still limited in number of cases, Magtrace® is a valid support in finding the SLN post NAC, both in terms of non-inferiority compared to Tc99, and as a complementary means to the latter in the 'to help us find a number ≥ 3 of LS, essential for breaking down the FNR.

Leiomyosarcomas represent the most common variant of uterine sarcomas, and are also considered to be the least chemosensitive. To date, adriamycin and ifosfamide are believed to be the most effective drugs for its treatment, in addition to docetaxel and gemcitabine. Recently, the introduction of trabectedin has provided clinicians with another treatment option, and the drug may have some benefits for patients as it may allow for long-term treatment. We present the case of a patient who previously failed multiple cycles of chemotherapy and who was subsequently treated with 30 cycles of trabectedin as third-line therapy for multiple metastases of uterine leiomyosarcoma. During the treatment period, the dosage and dose interval of trabectedin were optimized because of the appearance of grade 4 hematological and gastrointestinal toxicity. Dose adjustments led to acceptable tolerability. Trabectedin was associated with a very good partial response, especially at the pulmonary and pancreatic levels, and stable disease was achieved at all metastatic sites. The patient is currently continuing treatment with trabectedin and has clinically stable disease after 2 years of therapy. This case report provides further evidence that trabectedin is a valid and well-tolerated therapeutic option that can be used in the long term in uterine leiomyosarcoma.

Introduction/Background The non-interventional NIMES-ROC phase IV trial (NCT02825420) evaluated trabectedin (Yondelis®)+pegylated liposomal doxorubicin (PLD) in real-life clinical practice, given in accordance with the marketing authorization to women with platinum-sensitive recurrent ovarian cancer (PSROC) regardless of prior anti-angiogenic treatment. Methodology We report the results of an interim analysis of the data from patients with PSROC treated with trabectedin+PLD within the approved schedule (PLD 30 mg/m² followed by 1.1 mg/m² trabectedin as 3-h/every 3 weeks). Eligible were adults with PSROC who have received ≥1 cycle of trabectedin+PLD before inclusion. The primary endpoint was to assess the progression-free survival (PFS) according to investigator criteria. Results Overall, 158 adult patients from 50 sites across Spain, Italy, Germany, France and Belgium were evaluated. Median number of trabectedin+PLD cycles received per patient was 6, with 95 patients (50.6%) receiving ≥6 cycles and up 34 cycles. Median treatment duration and cycle duration were 22.2 weeks (range: 3–124) and 25.5 days (range: 21.0–73.0), respectively, with ≥63% of patients treated on an outpatient basis. Twenty-two patients received prior PLD or doxorubicin with no reported safety issues due to retreatment with trabectedin+PLD. With 73 PFS events and 32 deaths recorded, median PFS and overall survival were 11.4 months (95% CI: 10–14) and not reached (16.8-nr), respectively. The objective response rate was 38%, while 28.5% of patients had disease stabilization for a disease control rate of 66.5%. A total of 108 trabectedin-emergent adverse reactions (TEARs) occurred. Most common grade 3/4 TEARs were neutropenia (25%) and asthenia (4%). Conclusion Acknowledging the interim results from observational studies need to be interpreted with caution, our preliminary data confirm that trabectedin+PLD is effective and safe in patients with PSROC. Our data favourably compare with those of the pivotal OVA-301 trial (NCT00113607; i.e. median PFS 9.2 months), even with more pretreated patient population (NIMES-ROC: 39.9% with ≥3 prior chemotherapy lines). Disclosure Nothing to disclose.

The majority of patients with ovarian cancer will experience relapse and thus require second-line therapy. While platinum-based therapies are the primary treatments for refractory disease other options are required, particularly for those with partially platinum-sensitive disease as their response rates are lower. Agents that can resensitize relapsed ovarian cancers to platinum, including trabectedin, are therefore of increasing interest. Trabectedin is a multitarget agent that has a complex, novel mechanism of action and has exhibited promising results in platinum-sensitive ovarian cancer when in combination with pegylated liposomal doxorubicin (PLD). The present study conducted retrospective analysis involving 11 cases (median age 60 years; range 45-75 years) of recurrent ovarian tumors and partial platinum sensitivity undergoing treatment with trabectedin + PLD. The cohort consisted of 7 serous carcinomas, 1 endometrial carcinoma, 2 undifferentiated carcinomas, and 1 mucinous carcinoma. Of the 11 patients, 4 exhibited a complete response, 3 achieved stable disease, and 4 had progression of disease. Mean overall survival was 32.42 months and median progression-free survival was 5.9 months. Trabectedin in combination with PLD was well tolerated in terms of gastrointestinal and hematological toxicity; Grade 3 cutaneous toxicity and grade 3 neutropenia were each observed in 18.2% of patients. There were no grade 4 events. Thus, the present study supports the use of trabectedin + PLD in patients with relapsed ovarian cancer and partial platinum sensitivity, with predictable and manageable toxicity.

Isolated parenchymal splenic lesions are very rare and may occur as recurrences in the form of epithelial tubo-ovarian cancer (ETOC). We report a case of solitary parenchymal splenic recurrence of ETOC, which developed 50 months after the initial treatment. A 66-year-old woman underwent laparotomic primary cytoreduction in 2008. After platinum-based chemotherapy, she developed recurrences; thus, she underwent secondary and tertiary cytoreduction in 2011 and 2012 respectively. In April 2013, CT scan documented a solitary parenchymal splenic lesion and it was confirmed by FDG PET/CT. She underwent quaternary cytoreduction by laparoscopic splenectomy. Histopathological evaluation revealed metastatic parenchymal disease consistent with recurrent ETOC. She was alive and disease-free for ten months since splenectomy. In literature there are 35 cases of isolated spleen parenchymal metastasis of ETOC and our report is the first case of laparoscopic splenectomy in the setting of quaternary cytoreduction. Laparoscopic splenectomy as quaternary cytoreduction is safe and feasible and could be congruent to the well-established experiences already reported for the primary, secondary or even tertiary cytoreduction where the absence of residual disease has been translated in a significant survival benefit.

Pediatric nuclear medicine refers to imaging examinations performed in babies, young children, and teenagers. Carrying out nuclear medicine procedure on children requires a completely different approach than on adults. The complexity of the examination varies depending on the age of the patient, the degree of cooperation, clinical conditions, and duration of scintigraphic acquisition. Depending on the increasing complexity of pediatric nuclear medicine studies, a higher level of department expertise is necessary for the delivery of good quality examination and safe patient care.

Introduction The occurrence of preeclampsia before the 20th week of gestation is rare and it has been associated with hydatidiform molar pregnancy. Objectives We describe a case of first trimester eclampsia which occurred in a patient with hydatidiform mole. Methods Case report. Results A 16-year-old woman came to emergency service for abdominal pain and vaginal bleeding. She had been suffering of vomiting after meals and complaining for abdominal mass for 2months, without consulting her physician. The last reported period was 1month before; the patient told her periods were regular and the only disease she reported was chronic HBV hepatitis. Vital parameters were all normal. Urine pregnancy test resulted always negative. The gynecological exam reported an increased uterus and a little bleeding, so serum bhCG was performed because of the exam findings and resulted 110,5317UI/L. The transvaginal ultrasound showed images consistent with gestational trophoblastic disease. Computed tomography (CT) scan revealed the presence of an uterine mass and three lung nodules, reported as possibly metastatic. A few days later, the patient underwent dilation and curettage (D&C). Second grade hydatiform mole was diagnosed by histology. After D&C, the serum bhCG was 202,511UI/L. The day after, the patient presented bilateral acute blindness, followed by incoming general seizures, concurrent hypertension and tachycardia. Intravenous diazepam, levetiracetam and mannitol controlled the seizures, but the conscious state of the patient remained critical. Temperature reached 40°C, with concurrent leukocytosis. Then, a lumbar puncture was performed but it resulted negative for inflammatory/infective processes. A head CT was performed the same day and showed a posterior reversible encephalopathy syndrome (PRES). Intravenous methylprednisolone was started. Long term therapy with methylprednisolone and levetiracetam was effective and the patient's status improved and stabilized. A subsequent chemotherapy with EMA/CO regimen (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine/oncovine) was performed for six cycles, until serum bhCG resulted negative and the abdomen/pelvis ultrasound, head NMR and chest X-ray resulted normal. Conclusion Preeclampsia and eclampsia are regarded as common causes of PRES, which is considered to be the result of vasogenic brain edema. Clinical and imaging findings are usually reversible. Early diagnosis and elimination of possible causes are important in order to avoid permanent visual or brain injury. Imaging (especially MRI) should be carried out in eclamptic patients with visual disturbance in order to exclude other causes of blindness. Molar pregnancy is a rare but important cause of eclampsia, and it has always to be considered in case of early manifestations.

The bcl-2 protein is a membrane protein involved in prolonging cell survival by inhibiting apoptosis. The HER-2 oncogene, which is located on chromosome 17 and encodes for a tyrosine-kinase growth factor receptor, is amplified and HER-2/neu is overexpressed in 25% to 30% of breast carcinomas. The authors analyzed the bcl-2 expression and the bcl-2 gene and HER-2/neu overexpression and amplification in FIGO stage IIIC, serous, G3, ovarian carcinomas obtained from living patients who had no evident disease 5 years after primary treatment compared with ovarian carcinomas obtained from patients, matched for stage, grade of differentiation, and treatment, who had died of progression of disease no later than 2 years after primary treatment. bcl-2 overexpression was statistically correlated with progression of disease during first-line chemotherapy (P=0.021). The HER-2/neu status was found not to correlate with progression of disease during first-line chemotherapy. Both bcl-2 and HER-2/neu expression were not statistically associated with the clinical outcome of ovarian cancer patients. Gene amplification of the HER-2/neu chromosome 17 was found in all the HER-2/neu, 3+ score, positive-staining ovarian carcinomas. None of the analyzed samples revealed a translocation t(14;18)(q32;q21) in the bcl-2 gene. The knowledge of additional prognostic or even predictive factors, such as bcl-2 expression, in patients with advanced ovarian carcinoma before the primary chemotherapeutic treatment may help in the management of patients who require a more tailored treatment. In addition, the gene amplification of the HER-2/neu suggests that HER-2 is a potential target for treatment in ovarian cancer.

Background Significant progress has been made in understanding the molecular biology of ovarian carcinoma. Along with the molecular characteristics of cancer, the patient's response to the tumour may also contribute to survival; in particular, the effect of the immune system may play an important role on survival of cancer patients. Patients and methods We analysed the CD3 positive tumour-infiltrating T cells and direct molecular assessment of T cell receptors (TCRs) gamma and beta in 95 advanced ovarian carcinomas. Results Gamma/delta T cells are statistically correlated with a brief disease-free interval (P = 0.036). CD3 positive tumour-infiltrating T cells are correlated with a brief disease-free interval and with survival (P = 0.004 and P = 0.0001, respectively). CD3 positive tumour-infiltrating T cells are associated with clinical responsiveness to chemotherapy (P = 0.003). Conclusions Further studies are required to better understand the role of gamma/delta T cells in ovarian carcinoma, yet these data underline the importance of host immune response to cancer and the need to better study immune mechanisms to modulate the therapeutic treatment of cancer.

Purpose: Uterine leiomyosarcomas are rare tumors characterized by their resistance to chemotherapy and radiation treatment. Surgery is the primary method of treatment, but for patients with unresectable disease, alternate therapeutic options are clearly warranted. According to initial observations of c-KIT expression, correlation with a bad prognosis, and the successful therapeutic possibility of STI571 in gastrointestinal stromal tumors, the data have encouraged us to study c-KIT expression in these tumors. Experimental Design: We analyzed the expression of c-KIT and genetic assessment of exon 11 of c-kit gene in 32 uterine leiomyosarcomas. Results: In 17 cases (53.1%), we observed a c-KIT expression in tumor cells. Of the 17 patients with distinct c-KIT-positive immunoreactivity, eight had I or II stage disease and nine had III or IV stage disease. Molecular genetic analysis of exon 11, analyzed by direct DNA sequencing, was performed for all of the c-KIT-positive uterine leiomyosarcomas. No mutations were found. Conclusion: The conventional chemotherapy in leiomyosarcomas appears to be ineffective for patients with metastatic or unresectable disease, and the management of these patients poses a special problem. In these women, new therapeutic strategies are warranted. The treatment with STI571 in leiomyosarcoma patients might be hypothesized, because uterine leiomyosarcomas also express c-KIT.

Background Recent studies have shown that several tumours express c-KIT, a growth factor receptor with tyrosine kinase activity; moreover, clinical results have shown the efficacy of the tyrosine kinase inhibitor, STI571, in c-KIT-positive tumours. The aim of this study was to determine the incidence and correlation with chemotherapy resistance of c-KIT expression in advanced serous, low grade of differentiation, ovarian carcinoma. Patients and methods We performed an immunohistochemistry analysis of 56 patients with advanced serous ovarian carcinomas using archival paraffin-embedded specimens. Results Intense c-KIT immunostaining was observed in 51.7% of cases. c-KIT expression was statistically correlated with progression of disease after first-line chemotherapy (P = 0.029). Conclusions c-KIT is also expressed in ovarian carcinoma and it is statistically correlated with chemotherapy resistance. This study suggests the necessity for clinical trials confirming the utility of the tyrosine kinase inhibitor, STI571, in ovarian advanced cancer patients with c-KIT overexpression when these patients have shown no clinical response to conventional chemotherapy.

Purpose: A correlation of treatment for uterine sarcoma with outcome, prognostic importance of pathology, and clinical parameters. Patients and Methods: One hundred forty-one patients (median age: 56 years, range: 19 - 85 years) with a histologically verified uterine sarcoma were identified from a database compiled at the Royal Marsden Hospital and the University of Florence between 1974 and 2001. Seventy-two patients had leiomyosarcoma, 42 had mixed mullerian tumors, 22 had endometrial stromal sarcoma, 1 hemangiopericytoma, 1 rhabdomyosarcoma, and 3 patients had unspecified sarcoma. According to FIGO classification, Stage I, II, III, and IV tumors were identified in 71, 13, 31, and 26 patients, respectively. Results: At the time of analysis, 73.7% of patients were dead, and 26.3% were alive with a median survival of 2 years from initial diagnosis. Univariate analysis for cause-specific survival demonstrated statistical significance for histology (p 0.02), grade (p 0.003), stage (p 0.007), and age (p 0.02). Multivariate analysis demonstrated significant prognostic values for stage ( p 0.02) and histology (p 0.05) only. Postoperative radiotherapy with a total dose higher than 50 Gy seems to be significant ( p 0.001) in reducing local recurrence. Conclusions: Our data favor treatment for Stages I, II, and III of uterine sarcoma with radical surgery plus radical dose irradiation comprising both external beam radiotherapy and brachytherapy. © 2003 Elsevier Inc. Brachytherapy, Radiotherapy, Uterine sarcoma.

The aim of this study was to test the prognostic value of p-glycoprotein expression and the proliferative index of tumor cells on the clinical response to chemotherapy, on the brief disease-free interval (< 12 months) and on cause-specific survival in advanced ovarian carcinoma. We evaluated 83 ovarian carcinoma patients homogeneous for stage, type and grade histological. Brief disease-free interval and cause-specific survival rates (Kaplan-Meier method) were compared using the log rank test. Multivariate analysis (Cox proportional hazards models) was used to determine the independent effect of each variable on prognosis. In the univariate analysis, P-glycoprotein expression (P < 0.0005) and proliferative index (P = 0.0003 and P = 0.0006) were independent predictors of survival and brief disease-free interval; residual disease was associated with survival (P = 0.021). In multivariate analysis (Cox proportional hazards models), P-glycoprotein expression (P = 0.001 and P = < 0.0005) and proliferative index (P = 0.081 and P = 0.041) were independent predictors of brief disease-free interval and survival. P-glycoprotein expression (P < 0.0005) and proliferative index (P = 0.008) were associated with clinical response to chemotherapy.

Uterine malignant stromal tumors are rare neoplasms characterized by fatal prognosis. At the moment no effective systemic treatment is available for metastases or recurrent disease. The drugs employed in advanced neoplasms are iposfamide, doxorubicin or epidoxorubicin, but the clinical response to chemotherapy is poor. Recent studies have shown that cells in gastrointestinal stromal tumors express a growth factor receptor with tyrosine kinase activity termed c-kit. Lately reports of efficacy of a specific anticancer drug with imatinib (ST1571) based on specific molecular abnormalities of proto-oncogene c-kit present in gastrointestinal stromal tumors induced us to identify the c-kit phenotype also in uterine leiomyosarcomas. These data may be useful for treating metastatic uterine leiomyosarcomas with increased c-kit kinase activity.

Gynecological oncologists are faced with an increasing proportion of geriatric ovarian cancer patients. Comorbidities are frequently a matter of concern in this age group, and what is adequate treatment for such patients is still debated. The aims of this study were to analyze the feasibility of standard surgery and chemotherapy in a series of elderly ovarian cancer patients (/=70 years) and to investigate the influence of age (70-75 vs75 years) on survival. We retrospectively evaluated 89 elderly patients treated at our department between 1985 and 2005. Comorbidities, type of surgical procedure, complications, drugs and schedules of chemotherapy, number of cycles, toxicity, and clinical outcome were registered. Comorbidities were present in 71.9%. Only six patients were inoperable. Among the 83 patients who underwent surgery, 76.4% received adequate surgical treatment. Severe postoperative complications occurred in 16.8%, operative mortality was zero. A total of 801 cycles of chemotherapy were administered to 77 patients (median 10; range 1-38). Overall, G3-G4 toxicity was documented in 61.0%. The rates of dose reduction, treatment delay, and discontinuation were 13.0%, 20.7%, and 3.9%, respectively. Patients who received adequate surgery and those with residual disease1 cm did significantly better than their counterparts (P= 0.04 and P0.001, respectively). No difference in survival according to age (70-75 vs75 years) was found. Standard surgery and chemotherapy were feasible in elderly ovarian cancer patients. The type of surgery and the amount of residual disease, but not the age of the patients, significantly influenced the clinical outcome.

CA-125 is elevated in the serum of the majority of ovarian carcinoma patients. Cyclooxygenase-2 is an enzyme whose synthesis is upgraded by several cytokines, growth factors, and tumor promoters.We analyzed cyclooxygenase-2, preoperative CA-125 levels, and CA-125 levels during chemotherapy in 41 FIGO stage III, grade 3, ovarian serous carcinoma patients in relation to survival with a logistic regression. The correlation of cyclooxygenase-2 expression and CA-125 preoperative level with clinical responsiveness to chemotherapy was studied according to Fisher's exact test. We compared 23 patients living with no evident disease five years after primary treatment to 18 patients who had died of progression of disease no later than two years after primary treatment.Cyclooxygenase-2 overexpression (p = 0.014 and p = 0.036) and preoperative CA-125 level (p = 0.012 and p = 0.029) were found to be independent predictors of survival in univariate and multivariate analyses. Cyclooxygenase-2 and CA-125 level were correlated to responsiveness to chemotherapy (p = 0.003 and p = 0.036, respectively; Fisher's exact test). The patients with a CA-125 level35 U/ml after two cycles of chemotherapy showed a longer survival (p = 0.008). The median preoperative CA-125 was 195 in high survival patients and 650 in low survival patients (p= 0.004, Wilcoxon Mann-Whitney test).Cyclooxygenase-2 overexpression and CA-125 levels may help the management of ovarian cancer patients, permitting the selection of more aggressive and tailored first-line therapy.

We analyzed in advanced ovarian serous G3 carcinoma the correlation between epidermal growth factor receptor (EGFR) overexpression and tumor angiogenesis and their relation with clinical outcome. Microvessel density (MVD) and vascular endothelial growth factor (VEGF) were statistically correlated with disease-free interval and death from disease both in univariate and multivariate analyses while EGFR expression was not correlated with clinical outcome. MVD was significantly associated with progression of disease during chemotherapy while VEGF and EGFR expression were not correlated with responsiveness to chemotherapy (Fisher’s exact test). VEGF expression was correlated with MVD (Fisher’s exact test). EGFR showed a trend to correlation with MVD. Further studies focusing on the use of angiogenesis inhibitors in addition to EGFR inhibitors on ovarian carcinoma cells may produce therapeutic strategies in the selection of tailored therapies in ovarian cancer patients.

Many studies have focused on cyclooxygenase-2 (COX-2) alterations as a critical step in the onset and progression of cancer. Moreover, a strong correlation between COX-2 and chemoresistance has been demonstrated in several carcinomas. Recently, COX-2 expression has been observed in uterine carcinosarcoma, osteosarcoma, and rhabdomyosarcoma. We investigated COX-2 expression in chemoresistant uterine leiomyosarcoma in 30 patients who had undergone surgical treatment. COX-2 expression was observed in 13 cases (43.3%). Of the 13 patients with distinct COX-2 positive immunoreactivity uterine leiomyosarcomas, 7 had stage I or II disease and 6 had stage III or IV disease. The expression of COX-2 in uterine stromal malignancies may reveal a therapeutic hypothesis in the context of uterine leiomyosarcoma molecular chemotherapeutic approach.

Purpose To correlate the treatment used in uterine sarcoma with outcome. The prognostic importance of pathology, clinical parameters and treatment are analyzed. Patients and methods Forty patients (median age, 59 years; range, 37-85) with histologically verified uterine sarcoma were identified from a database compiled at the University of Florence from 1980 to 2001. Patients were followed for a median of 54 months (range, 3 months to 10 years). Twenty-four patients had leiomyosarcoma, 12 patients had mixed mullerian tumors, and 3 patients had endometrial stromal sarcoma. Stage I, II, III and IV tumors were identified in 22, 2, 9 and 7 patients, respectively. High, intermediate, low and unspecified grade sarcoma occurred in 9, 4, 5 and 22 patients, respectively. Results At the time of analysis, 58% of patients had died and 42% were alive, with a median survival of 2 years from the initial diagnosis. Cause-specific survival for the entire group was 81%, 41% and 25% at 1, 3 and 5 years, respectively. In our series, univariate analysis for cause-specific survival did not demonstrate statistical significance for histology, grade, stage or age. There appeared to be a significant impact for postoperative radiotherapy in reducing local recurrence with a total dose higher than 50 Gy. Conclusions Our data favor treatment for uterine sarcoma with radical surgery plus irradiation, even in elderly patients.

Between January 1996 and December 2001, at the Department of Gynecology, Perinatology and Human Reproduction of the University of Florence, 49 ectopic pregnancies were submitted to medical treatment. The treatment schedule consisted of the administration of 100 mg of intravenous methotrexate (MTX). The patients included in this study fulfilled the following requisites: gestational period8 weeks; diameter of the ectopic gestational sac4 cm; serum level of human chorionic beta-gonadotropin (beta-hCG)5000 IU/ml; absence of clinical and ultrasound signs of tube rupture with initial hemoperitoneum; hematochemical tests compatible with chemotherapic treatment. All patients were followed with a dosage of serum beta-hCG repeated every 2-3 days after chemotherapy and with an ultrasound every 3-4 days. In case of documented success of treatment the patient was hospitalized for no more than 3 days after administration of the drug. In 1 case therapy took place in a day-hospital regimen. Medical treatment was effective in 35 patients out of 49 (71.4%) and led to negative beta-hCG in a median time of 11 days, with a range between 2 and 48 days. In the 14 non-responsive cases (28.6%), after a mean time of 6 days we proceeded to a traditional surgical approach or laparoscopy. In none of the cases did we find significant pharmacological toxicity, while in 9 patients (18.3%), severe painful symptoms appeared immediately after treatment, but resolved within 24 hours. Our results are interesting and in agreement with other experiences found in the literature. In our opinion, the advisability of a second administration in case of slow response, the comparison with an analogous intramuscular treatment, a more precise definition of the eligibility criteria, long-term follow-up of the patients, especially in case of subsequent pregnancies should all be further considered.

Cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), and microvessel density (MVD) have been reported to be significantly related to carcinogenesis and to tumoral progression. The aim of the study was to analyse immunohistochemically the overexpression of COX-2 and VEGF, and the MVD between one another, and also in relation with clinical outcome in ovarian carcinoma. We selected 52 patients with ovarian carcinoma homogeneous by stage, type and histological grade, surgical and chemotherapeutic treatment. Of these, 28 patients had died of progression of their disease within 2 years of their primary surgical treatment, while 24 patients were alive with no evident disease at 5 years from the primary surgical treatment. The differences of the COX-2 status, the MVD and the VEGF expression in the two groups of ovarian carcinoma patients with low and high survival rate, respectively, were calculated according to the Fisher's exact test and the logistic regression. The shift in location of MVD in the two groups of patients was calculated according to the Wilcoxon Mann-Whitney test. MVD was correlated with COX-2 and VEGF overexpression (P=0.009 and P=0.003, respectively), COX-2 and VEGF were correlated to one another (P=0.044). In logistic regression analysis, COX-2, VEGF, and MVD were significant (P=0.017, P=0.008, P

Objectives . Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) play a critical role in cancer development. We investigated iNOS and COX-2 expression in relation to clinical outcome in 78 International Federation of Gynecology and Obstetrics (FIGO) stage III ovarian serous carcinoma with a low grade of differentiation (G3). Methods . Disease-free interval and cause-specific survival rates (Kaplan–Meier method) were compared using the log rank test. A multivariate analysis (Cox-proportional hazards models) was used to determine the independent effect of each variable on prognosis. Fisher's exact test was used to analyze the distribution of iNOS and COX-2 expression according to clinical complete response to chemotherapy and to the presence of a brief disease-free interval (≤12 months). Results . Overall 60 and 125 months cause-specific survival rates were 32% and 11%, respectively. In univariate analysis, iNOS ( P = 0.005 and P = 0.003, respectively), COX-2 ( P = 0.002 and P = 0.007, respectively), residual disease after surgery ( P = 0.017 and P = 0.032, respectively), and FIGO stage ( P = 0.008 and P = 0.025, respectively) were associated with survival and a disease-free interval. In multivariate analysis (Cox proportional hazards models), the factors that were found to be significantly independent predictors of disease relapse as well as survival were iNOS ( P = 0.014 and P = 0.001, respectively), COX-2 expression ( P = 0.007 and P = 0.029, respectively), and FIGO stage ( P = 0.026 and P = 0.05, respectively). iNOS and COX-2 expressions were correlated with a brief disease-free interval ( P = 0.001) and clinical complete response to first-line chemotherapy ( P = 0.038 and P = 0.033, respectively). Conclusions . The evaluation of iNOS and COX-2 expression may give additional prognostic information concerning the clinical outcome of patients with ovarian carcinoma and may encourage them to select more tailored therapies.

The aim of our study was to evaluate the possible prognostic and predictive significance of the expression of P-glycoprotein, a transmembrane transport protein related to multidrug resistance, in previously untreated patients with FIGO stage III ovarian cancer; to compare the results of immunocytochemical analysis of tissue sections of tumors to the in vitro chemosensitivity to cytotoxic drug of fresh samples of the same tumors; and to evaluate survival in women who underwent the same surgical treatment and the same adjuvant chemotherapy.

Primary and secondary mucinous tumors can involve the ovaries and have similar histologic appearances. The differential diagnosis is important for surgical and chemotherapeutic treatment and for the prognosis, but often it is extremely difficult. This article discusses an immunohistochemical panel that includes carcinoembryonic antigen (CEA), cytokeratin (CK) 7, CK20, CA125, CA19.9, and a new marker, CDX-2, for the distinction between primary ovarian mucinous carcinomas and metastatic (intestinal) ovarian tumors. Forty-three cases representing primary and secondary ovarian tumors were considered and consisted of 14 primary mucinous ovarian carcinomas (PMOCs) and 29 secondary (intestinal) ovarian tumors (SIOTs). Fisher exact test was performed to evaluate the reliability of the respective antibodies to discriminate between PMOCs and SIOTs. CDX-2 was diffusely positive in all SIOTs and was expressed focally in 3 cases (21.42%) of PMOCs. CK7 was diffusely positive in 13 cases (44.82%) of SIOTs and in 13 cases (92.85%) of PMOCs. CK20 was diffusely positive in 17 cases (58.62%) of SIOTs and in 6 cases (42.85%) of PMOCs. CEA was diffusely positive in 28 cases (96.55%) of SlOTs and in 12 cases (85.71%) of PMOCs. CA 19.9 was positive in all SIOTs and in 12 cases (85.71%) of PMOCs. CA125 was positive in 3 cases (10.34%) of SIOTs and in 4 cases (28.57%) of PMOCs. CK7 and especially CDX-2, a specific and sensitive marker, can aid pathologists in making a differential diagnosis (P = 0.003 and P < 0.0005, respectively), whereas CEA, CK20, CA125, and CA 19.9 markers are not high enough to distinguish between primary and secondary mucinous ovarian tumors.

Uterine leiomyosarcomas are associated with a poor prognosis, although a considerable diversity in behavior may be found, and prolonged survival may occur. The aim of this study was to analyze the expression of estrogen (ER) and progesterone (PR) receptors in tumor specimens from uterine leiomyosarcomas, and to test their correlation with disease-free interval and cause-specific survival. This additional information may help the clinician differentiate between patients who have minimal risk of recurrence and those at greater risk of developing progressive disease. We examined specimens from 31 uterine leiomyosarcoma patients with clinical history and known follow-up. Disease-free interval and cause-specific survival rates were calculated according to the Kaplan-Meier method. According to univariate analysis, with Cox proportional hazards models, the ER expression (P=0.006 and P=0.016, respectively), PR expression (P=0.005 and P=0.016, respectively), and FIGO stage disease (P=0.011 and P=0.007, respectively) were independent predictors of the risk of recurrence and death from disease.