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ABSTRACT: Background. This study aims at comparing the morbidity and oncologic outcomes in normal weight, overweight, and obese women with locally advanced cervical cancers (LACC) submitted to radical surgery after chemoradiation. Methods. A review of LACC patients with body mass index (BMI) ≥18.5 kg/m(2) who underwent neoadjuvant chemoradiation followed by radical surgery between January 1996 and December 2010 was performed. BMI categories were created according to the World Health Organization (WHO) classification. Results. Two hundred sixty-eight women met the inclusion criteria: 118 (44.0%) were normal weight, 100 (37.3%) overweight and 50 (18.7%) obese. The median follow-up was 42 months. Higher BMI was associated with older age (p = 0.0041), while there were no differences among the three groups in Charlson comorbidity score, tumor characteristics, radiotherapy dosing, type of surgery, and pathological response. There were no differences among the three groups in the intraoperative and postoperative complications as well as rate of patients requiring adjuvant treatments: 21 (7.8%) patients experienced grade 3-4 toxicity, including six normal weight, 12 overweight and three obese patients (p = 0.14). Only the rate of grade 1-2 skin toxicity was higher in obese (14%) with respect to overweight (1%) and normal women (0%) (p = 0.00001). There were no differences in the five-year DFS (74%, 77%, and 84% for normal weight, overweight, and obese women, respectively, p = n.s.), and five-year OS (76%, 78%, and 78% for normal weight, overweight, and obese women, respectively, p = n.s.). Conclusions. The role of obesity should not be overestimated when evaluating the chance of enrolment of LACC patients into preoperative chemoradiation protocols.
Acta oncologica (Stockholm, Sweden) 07/2012; · 2.27 Impact Factor
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ABSTRACT: In the last decades, the active research in the field of tumor angiogenesis has led to the development of a class of agents providing an effective inhibition of neo-vessel formation through the blockade of VEGF related pathways. More recently, the identification of other factors involved in tumor angiogenesis, such as platelet-derived growth factor, fibroblast growth factor and Angiopoietins has emphasized the need to develop agents targeting multiple pro-angiogenic pathways. Although contrasting data are currently available regarding the clinical efficacy of multikinase inhibitors, Sunitinib, Sorafenib and Pazopanib have displayed encouraging results, and have fuelled further evaluations. Moreover, definitive data are also eagerly awaited regarding the clinical role of angiopoietins inhibitors. On the other hand, the existence of morphological, functional and architectural differences between normal and tumor vasculature has provided solid basis for the development of a novel class of compounds, known as Vascular Disrupting Agents (VDAs) able to selectively disrupt existing tumor vessels. After initial concerns related to the potential development of severe cardiovascular toxicities, further clinical investigations have shown a safe toxicity profile for these agents. Moreover, despite the discouraging data on dolostatin-10 and ASA404, several VDAs, including CAP4, Ombrabulin and Pinabulin have already shown promising activity in phase I-II clinical trials warranting more advanced evaluations. In this review we aimed at summarizing the most relevant VEGF-independent strategies targeting tumor vasculature, focusing on the clinical development of novel antiangiogenic agents including multikinase and angiopoietins inhibitors as well as VDAs.
Current pharmaceutical design 02/2012; 18(19):2702-12. · 4.41 Impact Factor
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Sandro Pignata,
Giovanni Scambia,
Gabriella Ferrandina,
Antonella Savarese,
Roberto Sorio,
Enrico Breda,
Vittorio Gebbia,
Pietro Musso,
Luigi Frigerio,
Pietro Del Medico, [......],
Laura Scaltriti,
Stefano Greggi,
Carmela Pisano,
Domenica Lorusso,
Vanda Salutari, Francesco Legge,
Massimo Di Maio,
Alessandro Morabito,
Ciro Gallo,
Francesco Perrone
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ABSTRACT: Carboplatin/paclitaxel is the standard first-line chemotherapy for patients with advanced ovarian cancer. Multicentre Italian Trials in Ovarian Cancer-2 (MITO-2), an academic multicenter phase III trial, tested whether carboplatin/pegylated liposomal doxorubicin (PLD) was more effective than standard chemotherapy.
Chemotherapy-naive patients with stage IC to IV ovarian cancer (age ≤ 75 years; Eastern Cooperative Oncology Group performance status ≤ 2) were randomly assigned to carboplatin area under the curve (AUC) 5 plus paclitaxel 175 mg/m(2) or to carboplatin AUC 5 plus PLD 30 mg/m(2), every 3 weeks for six cycles. Primary end point was progression-free survival (PFS). With 632 events in 820 enrolled patients, the study would have 80% power to detect a 0.80 hazard ratio (HR) of PFS.
Eight hundred twenty patients were randomly assigned. Disease stages III and IV were prevalent. Occurrence of PFS events substantially slowed before obtaining the planned number. Therefore, in concert with the Independent Data Monitoring Committee, final analysis was performed with 556 events, after a median follow-up of 40 months. Median PFS times were 19.0 and 16.8 months with carboplatin/PLD and carboplatin/paclitaxel, respectively (HR, 0.95; 95% CI, 0.81 to 1.13; P = .58). Median overall survival times were 61.6 and 53.2 months with carboplatin/PLD and carboplatin/paclitaxel, respectively (HR, 0.89; 95% CI, 0.72 to 1.12; P = .32). Carboplatin/PLD produced a similar response rate but different toxicity (less neurotoxicity and alopecia but more hematologic adverse effects). There was no relevant difference in global quality of life after three and six cycles.
Carboplatin/PLD was not superior to carboplatin/paclitaxel, which remains the standard first-line chemotherapy for advanced ovarian cancer. However, given the observed CIs and the different toxicity, carboplatin/PLD could be considered an alternative to standard therapy.
Journal of Clinical Oncology 08/2011; 29(27):3628-35. · 18.37 Impact Factor
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ABSTRACT: Cyclooxygenase-2 overexpression is associated with poor outcome and resistance to platinum-based chemotherapy in ovarian cancer. We evaluated the antitumor activity and safety of the combination carboplatin plus the COX-2 inhibitor celecoxib in recurrent heavily-treated OC patients.
Patients were administered oral celecoxib (400 mg/day) in combination with intravenous carboplatin (AUC5, q28). A Simon's two-stage design was employed.
45 patients were enrolled: 23 (51.1%) presented platinum-resistance, and 27 (60%) had received at least 3 prior regimens for recurrence. The response rate was 28.9% with 3 complete and 10 partial responses (median duration of response = 6 months). Only one (0.4%) G4 non-febrile neutropenia was observed; G3 neutropenia, anemia, or thrombocytopenia, were observed in 2.5%, 1.7%, and 1.7% of the cycles, respectively. G3-4 vomiting was reported in only 1.7%, and 0.4% of the cycles were associated with G3 dyspepsia or diarrhea or constipation. Only one patient experienced G3 hypertension associated to G2 hypersensitivity reaction. No differences in baseline versus post-treatment Quality of Life scores were observed. Median progression free survival and overall survival were 5 and 13 months, respectively.
Celecoxib combined with carboplatin showed promising activity and it is well tolerated in heavily-treated recurrent ovarian cancer patients.
NCT01124435 (ClinicalTrials.gov Identifier) and 935/03 (study ID numbers).
BMC Cancer 01/2011; 11:214. · 3.01 Impact Factor
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ABSTRACT: Cervical cancer (CC) remains an important health problem. It is the second most frequent malignancy in women worldwide, with one-third of patients dying from pharmacoresistant disease.
We reviewed pharmacotherapy approaches in the medical and multidisciplinary management of CC and conducted a systematic search of Pubmed for clinical trials, reviews and meta-analysis published in the last 20 years. Abstracts of the American Society of Clinical Oncology, European Society of Gynecological Oncology and International Gynecologic Cancer Society were also searched, together with the US National Institutes of Health clinical trial database.
The state-of-the art of cytotoxic and biologically targeted therapies in early, locally advanced and metastatic/recurrent CC is discussed.
Until recently, the role of pharmacotherapy in CC was restricted to palliation of advanced/metastatic or recurrent disease. During the past two decades, this reluctant attitude towards chemotherapy has been modified after a series of randomized trials demonstrated its beneficial contribution as an adjunct to radiotherapy or surgery in early and locally advanced CC. Moreover, new combinations of cytotoxics, together with novel molecular target agents, open new perspectives in the treatment of primary and recurrent CC.
Expert Opinion on Pharmacotherapy 08/2010; 11(12):2059-75. · 3.20 Impact Factor
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Gabriella Macchia,
Gabriella Ferrandina, Francesco Legge,
Francesco Deodato,
Valeria Ruggieri,
Domenica Lorusso,
Gilbert D A Padula,
Vincenzo Valentini,
Numa Cellini,
Giovanni Scambia,
Alessio G Morganti
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ABSTRACT: The aim of this phase II study was to evaluate response and toxicity of a prolonged chemoradiation regimen in patients with locally advanced cervical cancer.
Three cycles of concomitant chemotherapy were used with cisplatin (20 mg/m², 2-hour intravenous infusion, days 1-4) and 5-fluorouracil (1000 mg/m², 24-hour continuous intravenous infusion, days 1-4) administered at weeks 1, 5, and 9 of radiotherapy. In combination, radiotherapy was delivered to a planning target volume (PTV) defined as the CTV (clinical target volume) plus 8 mm. The CTV was defined as follows: gross tumor volume, upper half of the vagina (if not involved) or the whole vagina (if clinically involved), uterus, obturator nodes, external iliac nodes, internal iliac nodes, and the presacral nodes (cranial to S2). The prescribed dose to the PTV was 50 Gy, 2 Gy/fraction (ICRU 62) delivered in 25 fractions with a 2-week break at 20Gy and 40 Gy (split-course technique). Early and late toxicity was assessed according to the RTOG and RTOG/EORTC toxicity scales. Perioperative toxicity was evaluated according to the Chassagne classification of surgical complications.
A total of 25 patients were included in this study. Median age was 52 years (range, 28-69). Clinical stage was: IB2-II: 19 patients (76%), III-IVA: 6 patients (24%). All patients completed the prescribed dose of chemoradiation and were evaluated 4 weeks after the end of treatment. Complete and partial clinical local response was observed in 4 and 19 patients, respectively (totaling 92% of clinical responses). About 32% of patients experienced grade 3 to 4 toxicity, in particular, grade 3 or 4 hematological toxicity was observed in 7 patients and 1 patient developed grade 3 genitourinary toxicity. No patients developed grade 3 gastrointestinal toxicity or skin toxicity. Of total, 22 patients (88%) underwent radical hysterectomy. Seven patients (28%) showed a complete response (CR) to treatment, and 7 patients (28%) showed microscopic residual disease (μPR), totaling 14 patients (56%) complete/partial microscopic responses. Perioperative morbidity was higher than reported in historical controls especially in terms of tissue fibrosis (64%) and perioperative urinary toxicity (14%). Actuarial 2-year local control, disease-free survival, and overall survival were 65.5%, 61.8%, and 80.8%, respectively.
A prolonged treatment with more chemotherapy courses does not improve tumor response and increases the risk of perioperative complication. This treatment regimen, considering the low incidence of acute gastrointestinal toxicity, might be tested in the adjuvant setting.
American journal of clinical oncology 12/2009; 33(6):577-82. · 2.21 Impact Factor
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ABSTRACT: Several evidences suggested that ovarian cancer (OC) patients showing isolated lymph node recurrence (ILNR) have an indolent evolution. The aim of the study was to retrospectively review ILNR observed in our Institution over the past 11 years in order to investigate: the pattern of disease progression after the first diagnosis of ILNR, and their clinical outcome.
Between September 1995 and September 2006, 523 epithelial OC were diagnosed in our centers, and 301 of these relapsed. Cases with a diagnosis of ILNR, and at least 12 months of follow up after the diagnosis of ILNR were included. Post-relapse survival (PRS) was recorded from the date of the diagnosis of ILNR to the date of death or date last seen. Survival probabilities were estimated according to the method of Kaplan and Meier and compared by the log rank test. Cox's regression model with stepwise variable selection was used to analyse the role of clinico-pathological parameters as prognostic factors for PRS.
Thirty-two cases were identified as ILNR (10.6% of the recurrences, and 6.1% of the OC population). Most of the patients continued to exhibit the same pattern of progression during follow up, with 75% of the patients free from peritoneal disease after 2 years from the diagnosis of ILNR. Median Post-Relapse Survival (PRS) was 37 months, and median Overall Survival (OS) was 109 months, with all patients surviving more than 2 years after the initial diagnosis. In multivariate analysis only Platinum-Free Interval (PFI) retained a prognostic role for PRS (p value = 0.033).
ILNR represents a less aggressive pattern of OC relapse which keeps progressing in the lymph nodes in a relatively high percentage of cases. On the other hand, the occurrence of peritoneal spreading after ILNR is associated with a rapidly fatal outcome.
BMC Cancer 01/2009; 8:367. · 3.01 Impact Factor
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ABSTRACT: We investigated the role of squamous cell carcinoma (SCC) at presentation (pre-SCC) and after treatment (post-SCC) as predictor of pathological response and outcome in locally advanced cervical cancer (LACC) patients undergoing preoperative chemoradiation.
One hundred and twenty-three consecutive LACC patients underwent preoperative chemoradiation including cisplatin and 5-fluorouracil plus external radiotherapy to the whole pelvic region. Clinical responders underwent radical surgery. SCC levels were expressed in nanograms/milliliter.
Ninety-five of 123 (77.2%) and 15/113 (13.3%) cases were classified as having high pre-SCC and high post-SCC levels. Complete pathological response was documented in 51 cases (41.5%), while persistence of microscopic foci was shown in 40 cases (32.5%). In the univariate analysis, FIGO (International Federation of Gynecology and Obstetrics) stage, clinical response to treatment and post-SCC levels were associated with pathological response to chemoradiation. In the multivariate analysis, only clinical response to treatment and post-SCC levels retained an independent role as predictors of pathological response to treatment. Cases with high post-SCC status had a shorter disease-free survival than cases with low post-SCC levels (p = 0.028). In the multivariate analysis, lack of a pathological complete response/persistence of microscopic foci to treatment retained an independent negative prognostic role for disease-free survival.
Post-SCC identifies LACC patients with a poor chance of pathological response to chemoradiation and an unfavorable outcome.
Oncology 02/2008; 74(1-2):42-9. · 2.27 Impact Factor
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ABSTRACT: To investigate in cervical cancer patients the impact of pre-treatment laparoscopic staging on treatment plan and disease free survival.
A review of the present literature has been performed and data have been compared to results obtained in a large series of patients not surgically staged.
Among 134 abstracts resulting from Medline research, 13 were deemed potentially relevant to the study questions. The presence of intraperitoneal diffusion of disease can be recognized in locally advanced cervical cancer patients (LACC) in a percentage ranging between 1.9% and 29%. The rate of aortic positive nodes in clinically negative LACC patients cases has been reported between 11% and 25%, by laparoscopy. In our Division, 152 LACC patients have been treated between October 1997 and February 2007. None of the patients has been submitted to pre-treatment laparoscopic staging, whereas in all cases a pre-operative MRI has been performed. With a median follow-up 28.0 months (range 3-126 months), 31 recurrences have been observed. The 5-year DFS has been 83% and OS 90%. Although only a retrospective analysis can be carried out, such result well compares to cases surgically staged.
Pre-treatment surgical staging can identify positive nodes in LACC patients considered clinically negative, and recognize intraperitoneal disease, thus making the physician tailor the treatment on the bases of histopathological result. Moreover, it offers the potential advantage of debulking of macroscopically positive nodes, and to transpose the ovary outside the radiation. However, the positive impact on DFS has still to be demonstrated.
Gynecologic Oncology 11/2007; 107(1 Suppl 1):S101-5. · 3.89 Impact Factor
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ABSTRACT: Gemcitabine (2',2'-difluorodeoxycytidine) (GEM) has been demonstrated to be active in the salvage setting of ovarian cancer (OC) patients.
A 57-year-old woman, with a diagnosis of FIGO Stage IIIC clear cell OC, judged inoperable to optimal residual tumor, was administered neo-adjuvant chemotherapy with carboplatin/paclitaxel/topotecan, and cytoreduction. After 5 months the patient progressed, and pegylated liposomal doxorubicin was started with rapid progression. GEM (1,000 mg/m2, d1,8,15, q28) was then started, and a complete clinical response was documented after seven cycles of treatment, and was maintained for 9 months; at progression fourth line carboplatin was attempted but 1 month after the last course of carboplatin, progression occurred, and the patient was re-challenged with GEM obtaining a partial response, of 6 months duration. Currently, the patient is still under treatment, without any complaints relative to her quality of life/specific symptoms.
We described the case of a drug resistant clear cell ovarian cancer showing a selective susceptibility only to GEM at first administration and at re-challenge. Moreover, this case expressed a molecular profile very likely to support high tumour cell sensitivity to GEM.
Cancer Chemotherapy and Pharmacology 09/2007; 60(3):459-61. · 2.83 Impact Factor
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ABSTRACT: Recurrence of disease represents a clinical challenge in ovarian cancer patients. The aim of this study was to analyse the distribution and pattern of recurrence and their association with clinical outcome in a large series of ovarian cancer patients. This study was conducted on 328 primary untreated ovarian cancer patients. For each relapse, information on date of clinical/instrumental recurrence, and pattern of disease presentation were retrieved. In stage III-IV cases (n = 270), diffuse abdominal carcinomatosis occurred in 62.1% of cases, while recurrences presented as a single lesion or multiple nodules occurred in 9.9% and 26.7% of cases, respectively. Pattern of recurrence as carcinomatosis was shown to be associated with unfavourable outcome even when stratified according to platinum free interval (PFI) duration. In multivariate analysis, pattern of recurrence and PFI duration retained an independent prognostic role for post-relapse survival. Duration of PFI and type of recurrence may independently influence post-relapse survival in ovarian cancer patients.
European Journal of Cancer 10/2006; 42(14):2296-302. · 5.54 Impact Factor
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Gabriella Ferrandina,
Franco Oreste Ranelletti, Francesco Legge,
Vanda Salutari,
Enrica Martinelli,
Andrea Fattorossi,
Domenica Lorusso,
Gianfranco Zannoni,
Valerio Vellone,
Amelia Paglia,
Giovanni Scambia
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ABSTRACT: We evaluated the effects of celecoxib treatment on tumor-infiltrating lymphocyte (TIL) subsets [CD3(+), CD4(+),CD8(+), CD25(+), and T cell receptor (TCR)-zeta-expressing cells] and tryptase-positive mast cells in cervical tumors. Circulating levels of cytokines [interleukin (IL)-1beta, IL-10, tumor necrosis factor-alpha, IL-6, and IL-12] and angiogenesis-modulating factors (vascular endothelial growth factor and endostatin) have also been analyzed.
Cervical tumor biopsies and blood samples were obtained at the time of diagnosis and after 10 days of celecoxib treatment (400 mg b.i.d., at 8:00 a.m. and 8:00 p.m.) in 27 cases. Immunohistochemistry and ELISA assays were used to assess the expression of biological factors in tumor tissue and circulating levels of cytokines and angiogenic molecules.
We showed a statistically significant increase in the percentage of TIL expressing the TCR-zeta chain after celecoxib treatment: indeed, in cases exposed to celecoxib, the percentage of TCR-zeta(+) cells ranged from 5.0 to 50.0 (median, 22.5) with respect to baseline expression (range, 3.0-50.0; median, 10.0; P = 0.0016). There was no significant treatment-related difference in the percentage of CD3(+), CD4(+), CD8(+), and CD25(+) TIL as well as in tryptase-positive cells. IL-12 levels were significantly reduced in posttreatment samples with respect to baseline levels (P = 0.002). We also found a reduction in the circulating levels of vascular endothelial growth factor, and a statistically significant increase of serum endostatin levels (P = 0.035).
We reported the first evidence in humans that celecoxib restores zeta expression by TIL in primary cervical tumors, suggesting that a positive modulation of immune function may serve as an additional mechanism supporting the antitumor effect of this class of drugs.
Clinical Cancer Research 05/2006; 12(7 Pt 1):2055-60. · 7.74 Impact Factor
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ABSTRACT: We have previously shown that corticotrophin-releasing hormone (CRH) inhibits the proliferation of Ishikawa (IK) human endometrial carcinoma cell line through the activation of CRH-R1 receptors. Here, we have further investigated the role of CRH and its type-1 receptor in the control of IK cell function, and we carried out a pilot study in tumor tissues obtained from 19 patients with endometrial cancer, looking at CRH-R1 gene expression. In the IK study, CRH counteracted the increase in cell proliferation caused by estradiol; type-1 receptors mediating this effect belong to the alpha subtype. In the study on human tumors, CRH-R1 was expressed in 4 out of 19 (21%) surgical specimens obtained from untreated patients with a diagnosis of primary endometrial cancer. Two out of 4 cases (50%) expressing CRH-R1 mRNA had extrauterine spreading of the disease, whereas cases not expressing CRH-R1 mRNA were all FIGO stage I, 2 (p=0.015).
Oncology Reports 03/2006; 15(2):375-9. · 1.84 Impact Factor
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ABSTRACT: Recent studies have demonstrated the overexpression of cyclooxygenase-2 (COX-2) in endometriosis. The aim of this study was to investigate the correlation between COX-2 expression and the clinical outcome rate in a homogeneous series of patients undergoing fertility-sparing complete laparoscopic ablation for severe endometriosis.
COX-2 expression was analysed by immunohistochemistry in 103 samples, 71 endometriomas (group 1) and 32 peritoneal implants and or recto-vaginal nodules (group 2) of endometriotic tissue from 85 patients submitted to complete laparoscopic ablation of severe endometriosis.
At median follow-up of 54 months, a recurrence rate of 24.7% (n = 21) was observed. Patients with COX-2-positive endometriotic cysts showed a lower relapse rate than COX-2-negative cases (16.7 versus 41.2%; P = 0.036). Patients with COX-2-positive peritoneal implant and or recto-vaginal nodule showed a similar trend. Taking the two groups of patients together, we found a significantly lower relapse rate in COX-2-positive patients in comparison to COX-2-negative patients (16.4 versus 40%; P = 0.0152). Moreover, COX-2-positive patients showed a longer relapse-free survival in comparison to COX-2-negative patients (P = 0.016).
In patients with severe endometriosis who underwent fertility-sparing complete ablation, COX-2 overexpression characterizes a subgroup of patients with lower risk of relapse and longer relapse-free survival.
Human Reproduction 11/2005; 20(10):2964-8. · 4.47 Impact Factor
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ABSTRACT: The aim of the study was to investigate by immunohistochemistry the expression of cyclooxygenase-2 (COX-2) in a single institutional series of borderline ovarian tumors (BOT). Moreover, to perform a comparative analysis, COX-2 expression was also analyzed in benign and malignant ovarian tumors.
Paraffin-embedded sections form 51 BOT, 26 benign, and 37 malignant ovarian tumors were incubated with polyclonal antiserum against COX-2. The results were calculated as the product of the percentage of the immunostained tumor cells by the relative staining score. Cases with immunostaining values of >1 were considered COX-2-positive.
Thirty-four (66.7%) of fifty-one BOT were considered as COX-2-positive, and this rate was not significantly different with respect to COX-2 positivity in benign (50.0%) and in malignant (51.3%) ovarian tumors (P value = 0.23). A significantly higher percentage of COX-2 positivity was found in serous (24 of 24, 100%) with respect to mucinous (9 of 26, 34.6%) BOT (P value = 0.0001). Moreover, 7 (63.6%) of 11 endocervical-type mucinous borderline ovarian tumors were COX-2-positive with respect to only 2 of 15 (13.3%) intestinal-type mucinous BOT (P value = 0.013). The same trend was observed in benign lesions, with COX-2 positivity in 9 of 11 (81.8%) of serous versus 4 of 15 (26.7%) of mucinous tumors (P value = 0.015). On the other hand, no difference was found in the percentage of COX-2 positivity in serous (14 of 29, 48.3%) versus mucinous (5 of 8, 62.5%) ovarian carcinomas (P value = 0.22).
COX-2 is differently expressed in BOT according to different histotype. Moreover, an increase of COX-2 positivity was observed from mucinous intestinal BOT to frankly malignant ovarian tumors suggesting that COX-2 overexpression might be involved in mucinous ovarian carcinogenesis.
Gynecologic Oncology 11/2004; 95(1):46-51. · 3.89 Impact Factor
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ABSTRACT: Malignant struma ovarii is a rare tumor, consisting of a struma ovarii with malignant transformation. The association of a malignant struma ovarii with pseudo-Meigs' syndrome and elevated Ca-125 levels has been never reported.
A 66-year-old woman presented with monolateral ovarian mass, ascites, hydrothorax, and elevated Ca-125 levels. Optimal medical staging was performed. Definitive histological examination revealed a malignant struma ovarii. The immediate and complete resolution of symptoms and rapid decline of both Ca-125 and thyroglobulin levels to normal value were achieved post-operatively. After counseling, strict follow-up was planned, and no adjuvant therapy was administered.
We report the first case of pseudo-Meigs' syndrome associated with malignant struma ovarii and elevated Ca-125 levels. The choice of not performing adjuvant therapy is feasible after optimal surgery and adequate staging procedure given to the usually clinical benign course and the low incidence of metastases in malignant struma ovarii. Careful patient counseling is required.
Gynecologic Oncology 08/2004; 94(1):226-8. · 3.89 Impact Factor
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ABSTRACT: The objective of the current study was to illustrate the influence of neoadjuvant therapy on the local immune response in patients with cervical carcinoma.
Uninvolved tumor-draining lymph nodes (TDLN) (n=158 lymph nodes), including internal, external, and common iliac lymph nodes as well as obturator, presacral, and aortic lymph nodes from 15 nontreated (NT) patients, 4 chemotherapy (CT)-treated patients, and 19 chemoradiation (CR)-treated patients, were analyzed for lymphocyte subset distribution and for the proliferative response of T cells to polyclonal activation and interferon-gamma (IFN-gamma) production. Lymphocyte subsets in peripheral blood also were assessed.
TDLNs from CR-treated patients contained higher proportions of CD8+ cells and natural killer cells than NT and CT-treated patients (P values ranged from <0.05 to <0.01). TDLNs from CR-treated patients were enriched in activated-type CD4+ cells (HLA-DR+, CD134+, CD62L-, and CD25+ at an intermediate expression level; P values ranged from <0.05 to <0.01) and activated-type CD8+ cells (CD62L-, P<0.001) compared with NT patients. Concomitantly, there was a reduction in the proportion of naïve-type CD4+ and CD8+ cells (CD45RA+/CD62L+) (P<0.01 and <0.05, respectively). CR treatment increased the proportion of both CD4+ and CD8+ cells prone to produce IFN-gamma. All TDLNs contained suppressive CD4+ T regulatory (Treg) cells (CD25+ and CD152+ at a high expression level) whose frequency and suppressive activity was not influenced by the treatment. Therapy-induced changes in TDLN were mirrored only in part by respective alterations in peripheral blood.
To our knowledge, the current study is the first to show that neoadjuvant therapy produces an enhancing effect on the immune competency of TDLNs from patients with cervical carcinoma.
Cancer 05/2004; 100(7):1418-28. · 4.77 Impact Factor
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ABSTRACT: The aim of this study was to analyze the clinical role of cyclooxygenase (COX)-2 in a large series of 175 cervical cancer patients.
Immunohistochemistry was performed on paraffin-embedded sections by using rabbit antiserum against COX-2. The tumor:stroma (T/S) ratio of COX-2 expression was used to define the overall COX-2 content in the tumor.
The T/S COX-2 ratio values ranged from 0.03 to 48.2 (mean +/- SE, 3.7 +/- 0.5). A total of 95 of 175 patients (54.3%) were scored as having a high (>1) T/S COX-2 ratio. In locally advanced cervical cancer patients who underwent neoadjuvant treatment, the percentage of cases showing a high T/S COX-2 ratio was greater in patients who did not respond to treatment (26 of 29 patients, 89.7%) than in patients with a partial (32 of 50 patients, 64.0%) or complete (19 of 44 patients, 43.2%) response (P = 0.0003). When logistic regression was applied, International Federation of Gynecologists and Obstetricians (FIGO) stage (chi(2) = 11.3; P = 0.0008) and T/S COX-2 ratio (chi(2) = 5.3; P = 0.021) retained an independent role in predicting a poor chance of response. Cases with a high T/S COX-2 ratio had a shorter overall survival (OS) [2-year OS, 61%(95% confidence interval 750-83)] than cases with a low T/S COX-2 ratio (2-year OS, 90%; 95% confidence interval, 81-99; P = 0.0001). In multivariate analysis, the status of T/S COX-2 IDV ratio, together with advanced stage, retained an independent negative prognostic role for OS.
The assessment of COX-2 status in both tumor and stroma compartment could provide valuable information to identify cervical cancer patients endowed with a very poor chance of response to neoadjuvant treatment and unfavorable prognosis.
Clinical Cancer Research 05/2004; 10(9):3117-23. · 7.74 Impact Factor
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ABSTRACT: Recent studies have demonstrated the overexpression of cyclooxygenase-2 (COX-2) in endometriosis. The aim of this study was to investigate the expression of COX-2 in different anatomical sites of endometriosis and its association with clinico-pathological parameters in a single institutional series of patients undergoing operative treatment.
COX-2 expression was analysed by immunohistochemistry in 136 samples of endometriotic tissue from 103 patients affected by endometriosis.
COX-2 immunoreaction was observed in 78.5% of ovarian endometriotic cysts, in 11.1% of peritoneal implants and 13.3% of recto-vaginal nodules. COX-2 positivity was not distributed differently according to age, pre-operative serum levels of CA125 and AFS score. Moreover, COX-2 positivity did not show any significant variation according to the subjective intensity of pain, as dysmenorrhoea, chronic pelvic pain, lower urinary tract or gastrointestinal symptoms, or according to infertility.
Increased COX-2 expression in the endometriotic ovarian cyst wall was observed with respect to other extraovarian localizations. No relevant correlations between COX-2 positivity and clinico-pathological characteristics and symptoms of patients were observed.
Human Reproduction 03/2004; 19(2):393-7. · 4.47 Impact Factor
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ABSTRACT: Cyclooxygenase-2 (COX-2) overexpression has been associated with parameters of tumor aggressiveness and unfavourable clinical outcome in several solid tumors. We investigated by immunohistochemistry the expression of COX-2 in normal vulvar tissue, non-neoplastic vulvar epithelial lesions, vulvar intraepithelial neoplasia (VIN) and invasive vulvar cancer (IVC).
The expression pattern of COX-2 was studied in normal vulvar tissue, in six cases of lichen sclerosus (LS), seven cases of squamous cell hyperplasia (SCH), 20 VIN, 2 Paget's disease and 36 IVC. The relationship between COX-2 expression and clinicopathologic parameters in IVC patients has been also addressed. Sections were incubated with normal rabbit serum for 15 min, then with rabbit polyclonal antiserum against human COX-2 (Cayman, Ann Arbor, MI, USA). The results were reported as mean +/- standard error (SE) of COX-2 integrated density values (IDV).
Higher levels of tumor/stroma COX-2 IDV ratio were found in stages III-IV (mean +/- SE = 3.5 +/- 0.8) than stages I-II disease (mean +/- SE = 1.4 +/- 0.3) (P value = 0.04). In the subgroup of stage I cases, tumor/stroma COX-2 IDV values were higher in cases with > 1 mm stromal invasion (T1b) than cases with <== 1 mm stromal invasion (T1a) (mean +/- SE = 1.6 +/- 0.3 vs. mean +/- SE = 0.6 +/- 0.1) (P = 0.033). Moreover, we observed higher tumor/stroma COX-2 IDV in cases with metastatic lymph node involvement than cases without lymph node involvement (mean +/- SE = 3.5 +/- 0.8 vs. mean +/- SE = 1.3+/-0.4) (P = 0.037).
This study suggests that COX-2 overexpression may contribute to vulvar tumorigenesis and progression. Moreover, the correlation of tumor/stroma COX-2 IDV ratio with tumor extension and metastatic lymph node involvement, which represent the major prognostic parameters in this neoplasia, implies that tumor/stroma COX-2 IDV ratio could have a prognostic role in vulvar cancer.
Gynecologic Oncology 03/2004; 92(2):537-44. · 3.89 Impact Factor
