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Biomedical subjects

G Scambia

Publications and source records attributed to G Scambia.

At least 19 recordsLinked to original sources
PubMed2007

Pegylated liposomal doxorubicin-related palmar-plantar erythrodysesthesia ('hand-foot' syndrome).

Palmar-plantar erythrodysesthesia (PPE), also called hand-foot syndrome or hand-to-foot syndrome, is a distinctive and relatively frequent dermatologic toxic reaction associated with certain chemotherapeutic agents. Pegylated liposomal doxorubicin (PLD), a long-circulating formulation of doxorubicin in which doxorubicin hydrochloride is encapsulated within pegylated liposomes, is approved to treat patients with metastatic breast cancer, advanced ovarian cancer, and acquired immunodeficiency syndrome-related Kaposi's sarcoma. The incidence of PPE is increased in patients receiving PLD compared with conventional doxorubicin. In studies that utilized the currently approved dose of PLD (50 mg/m(2) every 4 weeks), approximately 50% of all patients receiving PLD experienced PPE, and approximately 20% experienced grade 3 PPE. The pathophysiology of PPE, as it occurs with any drug with which it is associated, is not well understood. Studies evaluating the development of PPE specifically associated with PLD have not fully elucidated the mechanism; however, data support the roles of drug excretion in sweat and local pressure as contributors. When PPE develops, clinical interventions with respect to altering PLD administration include dose reduction, less frequent dosing, and ultimately, drug withdrawal with several consequences on treatment efficacy. This article will review the available data regarding the etiology and potential management strategies of PPE associated with PLD.

Antineoplastic Agents↗
PubMed2006

UbcH10 expression may be a useful tool in the prognosis of ovarian carcinomas.

The UbcH10 gene codes for a protein that belongs to the ubiquitin-conjugating enzyme family. Previous studies of our group suggest UbcH10 expression as a valid indicator of the proliferative and aggressive status of thyroid carcinomas. Therefore, to better understand the process of ovarian carcinogenesis, and to look for possible tools to be used as prognostic markers in these neoplasias, we decided to extend the analysis of the UbcH10 expression to the ovarian neoplastic disease. We found that the UbcH10 gene was upregulated in some ovarian carcinoma cell lines analysed. Then, immunohistochemical studies demonstrate that UbcH10 expression significantly correlates with the tumor grade and the undifferentiated histotype of the ovarian carcinomas. Furthermore, a significant relationship between UbcH10 expression and overall survival was observed. Finally, the block of UbcH10 protein synthesis by RNA interference inhibited the growth of ovarian carcinoma cell lines, suggesting a role of UbcH10 overexpression in ovarian carcinogenesis. Therefore, all these data taken together suggest the possibility to use UbcH10 detection as a marker for the diagnosis and prognosis of these neoplastic diseases and open the perspective of a therapy of some ovarian carcinomas based on the suppression of the UbcH10 synthesis and/or function.

Carcinoma↗
PubMed2006

Randomised study of systematic lymphadenectomy in patients with epithelial ovarian cancer macroscopically confined to the pelvis.

No randomised trials have addressed the value of systematic aortic and pelvic lymphadenectomy (SL) in ovarian cancer macroscopically confined to the pelvis. This study was conducted to investigate the role of SL compared with lymph nodes sampling (CONTROL) in the management of early stage ovarian cancer. A total of 268 eligible patients with macroscopically intrapelvic ovarian carcinoma were randomised to SL (N=138) or CONTROL (N=130). The primary objective was to compare the proportion of patients with retroperitoneal nodal involvement between the two groups. Median operating time was longer and more patients required blood transfusions in the SL arm than the CONTROL arm (240 vs 150 min, P<0.001, and 36 vs 22%, P=0.012, respectively). More patients in the SL group had positive nodes at histologic examination than patients on CONTROL (9 vs 22%, P=0.007). Postoperative chemotherapy was delivered in 66% and 51% of patients with negative nodes on CONTROL and SL, respectively (P=0.03). At a median follow-up of 87.8 months, the adjusted risks for progression (hazard ratio [HR]=0.72, 95%CI=0.46-1.21, P=0.16) and death (HR=0.85, 95%CI=0.49-1.47, P=0.56) were lower, but not statistically significant, in the SL than the CONTROL arm. Five-year progression-free survival was 71.3 and 78.3% (difference=7.0%, 95% CI=-3.4-14.3%) and 5-year overall survival was 81.3 and 84.2% (difference=2.9%, 95% CI=-7.0-9.2%) respectively for CONTROL and SL. SL detects a higher proportion of patients with metastatic lymph nodes. This trial may have lacked power to exclude clinically important effects of SL on progression free and overall survival.

Adult↗
PubMed2006

RB family members as predictive and prognostic factors in human cancer.

The retinoblastoma family members--pRb, pRb2/p130 and p107--are tumor suppressor genes involved in controlling four major cellular processes: growth arrest, apoptosis, differentiation and angiogenesis. Molecular genetic studies have identified abnormalities of these tumor suppressor genes in a large proportion of human cancers. These genetic alterations have emerged as significant factors in the pathogenesis and progression of many types of tumors and are therefore likely to provide relevant information to assess risk in cancer patients. There is a pressing clinical need to identify prognostic and predictive factors for patients with cancer, because there is an undeniable importance in being able to determine which patients will have a favorable outcome without further therapy (prognostic factor) and which will need some additional treatment (predictive factor). This review examines the predictive and/or prognostic role of each retinoblastoma family member in human cancer.

Female↗
PubMed2006

Postoperative ileus after para-aortic lymphadenectomy: a prospective study.

OBJECTIVE: To evaluate GI symptoms in patients submitted to systematic para-aortic lymphadenectomy (PALN) and to compare them in a contemporary series of patients only submitted to systematic pelvic lymphadenectomy (PLN). METHODS: A prospective study of 51 consecutive patients submitted to systematic (minimum number of aortic nodes removed > or =10) laparotomic para-aortic lymphadenectomy for any gynecological cancer. The following parameters have been monitored prospectively: nausea and vomiting, bowel movements, nasogastric tube insertion or reinsertion, the time of removal of the nasogastric tube, duration of ileus, time to first passage of stool, regular diet consumption and postoperative stay and complications. RESULTS: Twenty-three of 46 valuable patients (50%) submitted to systematic para-aortic lymphadenectomy complain of GI symptoms during recovery and 2 more cases have been readmitted for the appearance of nausea and vomiting with respect to 3 cases (5%) in the group of only pelvic lymphadenectomies (p=0.00001). According to multivariate analysis, the main determinant of post/operative GI dysfunction is the systematic aortic lymphadenectomy. Twenty-two out of a total of 28 symptomatic patients (78.6%) have accused mild symptoms and have been therefore treated by fasting, by intravenous fluid administration and by anti-emetic drugs. Out of the six remaining patients, three patients (10.7%) have been classified as moderate cases because they have required the insertion of a nasogastric tube for gastric decompression, whereas in the remaining refractory patients (10.7%, severe cases) prokinetics drugs have been used. An exploratory laparotomy has never been performed. CONCLUSIONS: GI dysfunction symptoms are very common in patients submitted to systematic para-aortic lymphadenectomy. However, only 20% of the patients complain about moderate/severe symptoms. In these cases, we strongly recommend a conservative management.

Aorta, Abdominal↗
PubMed2006

Ultrasound and color power Doppler in the detection of metastatic omentum: a prospective study.

OBJECTIVES: To analyze prospectively the ability of ultrasound to detect metastatic omentum in patients with suspicious pelvic masses and to describe the sonographic features of metastatic omental disease. METHODS: One hundred and eighty-four patients were evaluated preoperatively by ultrasound examination and of these 173 were used in the analysis. We defined as an ultrasound-positive examination one which visualized intra-abdominal aperistaltic solid tissue, located above the bowel loops and below the anterior peritoneal surface. Preoperative sonographic findings were compared with pathological results. RESULTS: Sonographic detection of metastatic omentum was achieved in 104 of 173 patients (60.1%), appearing as either solid aperistaltic tissue (80.8% of cases), or as solid discrete nodules (19.2%). When considering the echostructure of the surrounding bowel loops, this tissue appeared hypoechoic in 46 (44.2%) cases and isoechoic or slightly hyperechoic in the other 58 (55.8%) cases. In the overall series, the negative and positive predictive values (NPV and PPV) and the accuracy of ultrasound examination were 92.7%, 91.3% and 91.9%, respectively. When considering only the group of ovarian tumors, the NPV, PPV and accuracy were 91.9%, 94.6%, and 93.8%, respectively. CONCLUSION: Ultrasound examination is highly accurate in detecting metastatic omental involvement in cases with suspicious pelvic masses.

Adolescent↗
PubMed2006

Role of gemcitabine in ovarian cancer treatment.

Newer agents and combinations are needed in order to improve current results in ovarian cancer treatment. Gemcitabine is a novel agent that has shown promising activity as a single agent in the treatment of platinum-resistant ovarian cancer and a favorable toxicity profile. Because of its clinical and preclinical synergism with platinum analogues, Gemcitabine has been combined with Carboplatin as a convincing approach in the treatment of platinum-sensitive recurrent ovarian cancer patients. Further combination of Gemcitabine and other agents, including paclitaxel, are also feasible and have been actively studied in order to establish the role of Gemcitabine in the management of treated and untreated ovarian cancer patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

BRCA1 and BRCA2 genetic testing in Italian breast and/or ovarian cancer families: mutation spectrum and prevalence and analysis of mutation prediction models.

BACKGROUND: Breast cancer is an extremely complex disease, characterized by a progressive multistep process caused by interactions of both genetic and non-genetic factors. A combination of BRCA1 and BRCA2 gene mutations appears responsible for about 20%-30% of the cases with breast cancer familial history. The prevalence of BRCA1/2 pathogenic mutations largely varies within different populations; in particular, the rate of mutations in Italian breast and/or ovarian cancer families is rather controversial and ranges from 8% to 37%. PATIENTS AND METHODS: Of the 152 breast/ovarian cancer families counseled in our centre, 99 were selected for BRCA1/2 mutation screening according to our minimal criteria. The entire coding sequences and each intron/exon boundary of BRCA1/2 genes were screened by direct sequencing (PTT limited to BRCA1 exon 11). For each proband, the a priori probability of carrying a pathogenic BRCA1/2 germline mutation was calculated by means of different mutation prediction models (BRCApro, IC and Myriad Table) in order to evaluate their performances. RESULTS: Our analysis resulted in the identification of 25 and 52 variants in the BRCA1 and BRCA2 genes, respectively. Seventeen of them represent novel variants, including four deleterious truncating mutations in the BRCA2 gene (472insA, E33X, C1630X and IVS6+1G>C). Twenty-seven of the 99 probands harbored BRCA1 (n = 15) and BRCA2 (n = 12) pathogenic germline mutations, indicating an overall detection rate of 27.3% and increasing by more than 15% the spectrum of mutations in the Italian population. Furthermore, we found the lowest detection rate (19.4%) in pure hereditary breast cancer family subset. All of the prediction models showed praises and faults, with the IC software being extremely sensitive but poorly specific, compared to BRCApro. In particular all models accumulated most false-negative prediction in the HBC subset. Interestingly preliminary results of a study addressing the presence of genomic rearrangements in HBC probands with BRCApro or IC prediction scores >/=95%, provided evidence for additional mutations undetectable with our conventional screening for point mutations. CONCLUSIONS: Altogether our results suggest that HBC families, the largest pool in our series, represent an heterogeneous group where the apparently faulty performances of the prediction models might be at least partially explained by the presence of additional kinds of BRCA1/2 alteration (such as genomic rearrangements) or by mutations on different breast cancer related genes.

Adult↗
PubMed2006

From bio-molecular and technology innovations to clinical practice: focus on ovarian cancer.

Ovarian cancer (OC) still represents the most lethal of gynecological malignancies with the chance for death in 5 years exceeding the chance for life. In recent years, the development of knowledge in molecular biology of OC coupled with the new technologies offers enormous opportunity to learn about aetiology of OC, and also give us a powerful tool for early diagnosis, prognosis and treatment of this disease. In particular, small cancer specimens from patients have become extremely informative thanks to techniques such as laser capture microdissection (LCM), tissue lysate arrays (TLAs), reverse trascriptase polymerase chain reaction (RT-PCR), and mass spectrometry. All of this coupled with advancements in bioinformatics have allowed the explosion of genomics, transcriptomics and proteomics. This paper focusses on the influence that advancement in the "-omics" bio-technology will reserve in OC diagnosis, prognostic characterization, and treatment.

Biotechnology↗
PubMed2005

Endometrioid adenocarcinoma with squamous differentiation arising from ureteral endometriosis in a patient with no history of gonadal endometriosis.

BACKGROUND: Malignant transformation may occur in up to 1% of women with endometriosis and only 20% of these cases occur at extragonadal pelvic sites. Similarly, urinary tract endometriosis is rare and occurs in only 1% of all endometriotic lesions. CASE: An endometrioid carcinoma with squamous differentiation arising from periureteral endometriosis presented as a pelvic mass encasing the right ureter. The patient had a history of total hysterectomy and bilateral salpingo-oopherectomy 8 years earlier because of bilateral serous benign cysts with right hemorrhagic corpus luteum and uterine fibroids, and has since been under unopposed estrogen replacement therapy for 5 years. CONCLUSION: This is the second case of a malignancy arising in endometriosis presenting as an obstructive ureteral mass and the first case of a patient with this condition whose endometriosis is not consistent with a gonadal origin. An analysis of the case and related literature is presented together with the discussion of possible pathogenetic mechanisms.

Carcinoma, Endometrioid↗
PubMed2005

p53 Gene status and response to topotecan-containing chemotherapy in advanced ovarian carcinoma.

OBJECTIVE: Since the p53 gene has been identified as a determinant of response to chemotherapy in ovarian carcinoma in previous studies, we investigated the significance of the p53 status in response to topotecan as second-line therapy. METHODS: Twenty-eight patients with advanced ovarian carcinoma, pretreated with standard platinum/paclitaxel chemotherapy, received topotecan as single-agent second-line therapy. Tumors were investigated by molecular analysis for p53 mutations in tumor samples obtained at primary surgery (i.e. before first-line therapy). RESULTS: Wild-type p53 tumors responsive to first-line therapy maintained substantial responsiveness to topotecan. In contrast, p53 mutation was associated with a low responsiveness to second-line therapy. CONCLUSIONS: The better outcome in relapsed patients with wild-type p53 suggests that the presence of a functional wild-type p53 confers stability of the drug-sensitive phenotype. This outcome is consistent with the clinical observation that the efficacy of topotecan in the treatment of relapsed ovarian carcinoma patients is dependent on platinum sensitivity, because platinum-sensitive tumors are expected to carry wild-type p53. Although untreated mutant p53 tumors may be responsive to first-line paclitaxel-containing therapy, it is likely that loss of p53 leads to genomic instability resulting in rapid progression to drug resistance.

Aged↗
PubMed2005

Survivin expression in ovarian cancer and its correlation with clinico-pathological, surgical and apoptosis-related parameters.

We investigated the association of survivin expression with prognosis and other apoptosis-related biological factors in 110 primary ovarian cancer patients admitted to the Division of Gynecologic Oncology, Catholic University of Rome. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded sections by using polyclonal antibody ab469 for survivin, and mouse monoclonal antibodies (clone 124 and DO-7), for bcl-2 and p53, respectively. Cytoplasmic survivin immunoreaction was observed in 84.5% cases, while nuclear survivin immunostaining was observed in 29.1% cases. We failed to find any relationship between cytoplasmic survivin positivity rate and any of the parameters examined. Serous tumours showed a lower percentage of nuclear survivin positivity with respect to other histotypes (20.5 vs 48.6%, respectively; P-value=0.004). The percentage of nuclear survivin positivity was higher in cases subjected to primary tumour cytoreduction (43.5%), with respect to patients subjected to exploratory laparotomy (20%) (P=0.024). Bcl-2 and p53 were, respectively, expressed in 27.3 and 60.0% of the cases and their expression was not correlated with survivin status. During the follow-up period, progression and death of disease were observed in 68 (61.8%) and 53 (48.2%) cases, respectively. There was no difference in time to progression and overall survival according to survivin status in ovarian cancer patients. In conclusion, in our experience, the immunohistochemical assessment of survivin status does not seem to be helpful in the prognostic characterisation of ovarian cancer. A more in depth investigation of the complex physiology of divergent survivin variants is needed in order to clarify the biological and the clinical role of differentially located survivin isoforms.

Apoptosis↗
PubMed2005

Does quantitative analysis of three-dimensional power Doppler angiography have a role in the diagnosis of malignant pelvic solid tumors? A preliminary study.

OBJECTIVE: To investigate the role of a simplified method for the three-dimensional (3D) quantification of tumor vascularity in the differential diagnosis of solid pelvic masses. METHODS: Twenty-four patients with a solid pelvic mass on B-mode ultrasound evaluation underwent 3D power Doppler evaluation before surgery. The volume of interest was obtained by drawing the largest section of the mass in three orthogonal planes. The following 3D vascular parameters were calculated for all patients: relative color, average color and flow measure. Receiver-operating characteristics curve analysis was used to choose the best cut-off value. The overall agreement between the test result and the actual outcome was calculated using kappa statistics. RESULTS: Fifteen of 24 subjects were found to have pelvic malignancy. The relative color and the flow measure were significantly higher in malignant (9.7 (8.98) and 8.95 (8.78) (median (interquartile range (IQR)), respectively) than in benign masses (2 (4.42) and 1.79 (4.71), respectively; P < 0.05) but there was no difference in the average color. The best cut-off values of relative color and flow measure were 3.2 and 2.8, respectively. The use of relative color showed a sensitivity of 80% with a specificity of 67% with an overall agreement that was higher, though only marginally so, than that of qualitative 3D power Doppler (kappa = 0.47 and 0.44, respectively). CONCLUSIONS: In a small group of pelvic masses that appear malignant on B-mode ultrasonography, the use of 3D quantification of tumor vascularity yields a diagnostic accuracy that is similar to that of subjective evaluation of vascularity. We suspect, however, that the quantitative method will produce more consistent results between operators.

Adult↗
PubMed2005

Ultrasound features of different histopathological subtypes of borderline ovarian tumors.

OBJECTIVE: To describe the gray-scale sonographic and color Doppler imaging features of the most common histopathological subtypes of borderline ovarian tumors. METHODS: We analyzed retrospectively the preoperative transvaginal sonographic reports of patients with a histological diagnosis of borderline ovarian tumor. All patients were scanned consecutively by two of the investigators using transabdominal and transvaginal gray-scale imaging to assess the morphology and color Doppler to obtain indices of the blood flow. Sonographic findings were compared to histopathological data. RESULTS: A total of 113 consecutive cases were reviewed from two referral centers for gynecological oncology. At histological examination 50 tumors (44%) were classified as being serous borderline ovarian tumors (SBOT), 61 (54%) were mucinous borderline ovarian tumors (MBOT) (42 intestinal type and 19 endocervical type), and two patients (2%) presented with borderline endometrioid tumors. SBOTs and endocervical-type MBOTs had very similar sonographic features and a smaller diameter, fewer locules (usually unilocular-solid lesions) and a higher color score than intestinal-type MBOTs. Intestinal-type MBOTs were characterized by a significantly higher percentage of lesions with > 10 locules when compared with the endocervical-type MBOTs. CONCLUSION: Intestinal-type MBOTs have different sonographic features from other common borderline ovarian tumors.

Adult↗
PubMed2005

Skull metastasis in primary vulvar adenocarcinoma of the Bartholin's gland: a case report.

BACKGROUND: Metastatic bone involvement in vulvar squamous carcinoma is very rare. Here, we present a case of primary adenocarcinoma of the Bartholin's gland giving rise to isolated skull metastasis. CASE: A 74-year-old woman was referred with a diagnosis of primary vulvar adenocarcinoma of the right labium minus. A right hemivulvectomy was performed with ipsilateral inguinofemoral lymphadenectomy, revealing a primary adenocarcinoma of the Bartholin's gland and metastatic involvement in 6 out of 13 lymphnodes. During chemotherapy administration, the patient started complaining of a worsening of right hypoacousis. CT scan and MRI of the brain showed the presence of a metastatic lesion on the right side of the skullbone. The diagnosis was metastatic poorly differentiated adenocarcinoma. CONCLUSION: In adenocarcinoma of the Bartholin's gland at an advanced stage of disease, a bone scan or survey in the preoperative as well as follow up staging procedures could be useful.

Adenocarcinoma↗
PubMed2005

Progression of conservatively treated endometrial carcinoma after full term pregnancy: a case report.

INTRODUCTION: We describe a case of conservatively treated endometrial endometrioid (EE) adenocarcinoma which showed an aggressive clinical outcome after pregnancy. CASE: A 30-year-old woman with a well differentiated EE adenocarcinoma decided to attempt a conservative approach and underwent progestin treatment with subsequent negative ultrasound and hysteroscopic controls. After 3 months, she conceived and at 36 weeks of gestation, a cesarean section was performed with multiple negative biopsies. Eight 8 months after delivery, an exploratory laparotomy documented disseminated poorly differentiated EE adenocarcinoma. Staging work up revealed diffuse metastatic disease. Despite chemotherapy, the patient experienced progression of disease with fatal acute respiratory syndrome due to massive neoplastic pulmonary lymphangitis. CONCLUSION: Conservative medical management of endometrial cancer in young women willing to preserve their reproductive potential, carries on potential risks. Careful selection of cases, informed consent, and strict follow up procedures are mandatory.

Adult↗