First 100 early endometrial cancer cases treated with laparoendoscopic single-site surgery: a multicentric retrospective study.

OBJECTIVE: We sought to assess feasibility and perioperative outcomes for laparoendoscopic single-site surgery (LESS) in early endometrial cancer. STUDY DESIGN: This was a retrospective multicentric study of 100 early endometrial cancer cases undergoing LESS from July 2009 through July 2011. RESULTS: All patients underwent total hysterectomy and bilateral salpingo-oophorectomy by LESS. Pelvic and paraaortic lymphadenectomy were performed in 48 and 27 patients, respectively. A median of 16 pelvic lymph nodes (range, 1-33) and 7 paraaortic lymph nodes (range, 2-28) were retrieved. Both median operative time (129 minutes; range, 45-321) and estimated blood loss (70 mL; range, 10-500) were greater when staging lymphadenectomy was performed (P values = .001). Four intraoperative and 4 postoperative complications were observed. Conversion to standard laparoscopy and laparotomy was necessary for completion of 1 case each. Patients responded positively regarding cosmetic result and minimal postoperative pain control. CONCLUSION: LESS further minimizes the invasive nature of surgery and is feasible for treatment of early-stage endometrial cancer.

Phase II study of the combination carboplatin plus celecoxib in heavily pre-treated recurrent ovarian cancer patients.

BACKGROUND: 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. METHODS: Patients were administered oral celecoxib (400 mg/day) in combination with intravenous carboplatin (AUC5, q28). A Simon's two-stage design was employed. RESULTS: 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. CONCLUSIONS: Celecoxib combined with carboplatin showed promising activity and it is well tolerated in heavily-treated recurrent ovarian cancer patients. TRIAL REGISTRATION NUMBER: NCT01124435 (ClinicalTrials.gov Identifier) and 935/03 (study ID numbers).

Symptomatic vaginal bleeding in a postmenopausal woman revealing colon adenocarcinoma metastasizing exclusively to the vagina.

Vaginal carcinomas are rare entities, accounting for 2% of all malignant cancers of the female genital tract, and the vast majority are metastatic. Adenocarcinoma of the colon metastasizing to the vagina is extremely rare, only 5 cases have been reported. We present the case of a woman who experienced vaginal bleeding as an isolated symptom of vaginal metastasis of colorectal adenocarcinoma. Vaginal localization of metastasis from colorectal cancer significantly worsens the survival prognosis, and a standard treatment has not yet been proposed. Potential mechanisms of spread of colorectal cancer to the vagina and therapeutic approaches are discussed. In this case, treatment included surgery and chemotherapy.

Expression of class III beta tubulin in cervical cancer patients administered preoperative radiochemotherapy: correlation with response to treatment and clinical outcome.

OBJECTIVES: Alterations of the beta subunit of tubulin have been reported to be predictive of resistance to radiation and antitubulin agents in several solid tumors. The aim of the study was to investigate the clinical role of beta III tubulin expression as prognostic factor for survival and as a predictive parameter of response to preoperative radiochemotherapy in a single institutional series of locally advanced cervical cancer (LACC) patients. METHODS: The study included 98 LACC patients admitted to the Gynecologic Oncology Unit, Catholic University of Rome and Campobasso between January 1998 and January 2005. Immunohistochemistry was performed by using the polyclonal rabbit anti-beta III tubulin antibody (Covance, Princeton, NJ, USA). The value of 10% immunostained tumor cells was arbitrarily chosen as cut-off value to distinguish cases with high versus low beta III tubulin content. RESULTS: In the whole series, beta III tubulin immunoreaction was detectable in 66/98 cases (67.3%), and the percentage of positively stained cells ranged from 0 to 100% (median=10%). The percentages of cases with high beta III tubulin expression were shown not to be differently distributed according to clinico-pathological characteristics. There was no statistically significant difference in the distribution of cases with high beta III tubulin expression according to clinical and pathological response to treatment. During the follow-up period, recurrence and death of disease occurred in 15 and 13 cases, respectively. There was no difference in disease-free and overall survival in cases with high versus low beta III tubulin expression. CONCLUSIONS: The assessment of class III beta tubulin status seems of little usefulness in order to identify LACC patients with poor chance of response to concomitant radiochemotherapy and unfavorable prognosis.

Impact of pattern of recurrence on clinical outcome of ovarian cancer patients: clinical considerations.

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.

Cyclo-oxygenase-2 (Cox-2) expression and resistance to platinum versus platinum/paclitaxel containing chemotherapy in advanced ovarian cancer.

BACKGROUND: Cyclo-oxygenase-2 (COX-2), the key enzyme in the conversion of arachidonic acid to prostaglandins, is involved in critical steps of tumor onset and progression, and is a strong predictor of chemotherapy resistance and poor outcome in advanced ovarian cancer. To our knowledge, no data has been reported until now about the association between COX-2 status and response to different chemotherapy regimens. METHODS: A retrospective study was performed to investigate the association of COX-2 with outcome and response to platinum versus platinum/paclitaxel in 68 primary ovarian cancer. COX-2 immunoreaction was performed on paraffin-embedded sections by using rabbit polyclonal antiserum against COX-2. RESULTS: In the overall series, COX-2 positivity was found in a statistically significant higher percentage of not responding cases than in patients responding to chemotherapy (n = 15/21; 71.4% versus n = 17/47; 36.1%; p value = 0.0072). A higher percentage of COX-2 positivity was found in patients unresponsive (n = 11/13; 84.6%) versus patients responsive to platinum-based chemotherapy (n = 9/26; 34.6%). In cases administered platinum/paclitaxel, COX-2 positivity was found in 4 out of 8 (50%) of un responsive versus 8 out of 21 (38.1%) of responsive cases. Logistic regression analysis of parameters likely to affect response to treatment resulted in a p value = 0.17 for the interaction COX-2/type of treatment. CONCLUSION: Although these findings need to be confirmed in a larger series, our study suggests a possible indication that there is a difference in the influence of COX-2 on response depending on treatment regimen.

Class III beta-tubulin overexpression is a marker of poor clinical outcome in advanced ovarian cancer patients.

PURPOSE: Overexpression of beta III tubulin has been involved in paclitaxel resistance in several experimental models. We investigated the role of beta III tubulin as predictor of clinical outcome in ovarian cancer patients given platinum/paclitaxel treatment. We also investigated whether beta III tubulin expression could be modified after the selective pressure represented by chemotherapy in vivo. EXPERIMENTAL DESIGN: The study was designed to include a series of consecutive ovarian cancer patients with unresectable disease at time of first surgery, who underwent interval debulking surgery with pathologic assessment of response to treatment with platinum/paclitaxel chemotherapy. Immunostaining was done on formalin-fixed, paraffin-embedded tissue sections from pretreatment and posttreatment tissue biopsies by using the polyclonal rabbit anti-class III beta-tubulin antibody. RESULTS: beta III Tubulin immunoreaction was observed in 51 of 62 (82.2%) cases. beta III Tubulin positivity was neither associated with clinicopathologic variables nor with pathologic response to chemotherapy. Significantly lower percentages of beta III tubulin positivity were observed in posttreatment (range, 5-80%; median, 20%) versus pretreatment (range 10-100%; median, 40%) tissue biopsies (P = 0.0011). Cases with high beta III tubulin expression showed a worse overall survival with respect to cases with low beta III tubulin expression (median overall survival, 25 versus 46 months; P = 0.002). Multivariate analysis showed that high content of beta III tubulin remains independently associated with a worse prognosis. CONCLUSIONS: Assessment of beta III tubulin could be useful to identify poor prognosis ovarian cancer patients candidates to more aggressive and/or targeted therapy.

Anemia in patients with locally advanced cervical carcinoma administered preoperative radiochemotherapy: association with pathological response to treatment and clinical outcome.

OBJECTIVE: The aim of this study was to investigate the role of anemia at presentation (basal HB) and during treatment (nadir HB) as predictor of pathological response, as well as disease-free (DFS) and overall survival (OS) in LACC patients undergoing chemoradiation followed by radical surgery. METHODS: 114 consecutive LACC patients were accrued at the Gynecologic Oncology Unit, Catholic University, Rome and at the Department of Oncology, Catholic University of Campobasso, Italy. Neoadjuvant treatment included chemotherapy with cisplatin (20 mg/m2) and 5-fluorouracil (1000 mg/m2, 24-h infusion) (both on days 1-4 and 27-30) and external radiotherapy to the whole pelvic region (22 fractions, 1.8 Gy/day, totaling 39.6 Gy). Clinical responders underwent radical surgery. Hemoglobin levels were recorded and expressed in gram per literx10(-2) (g/dl). The value of 10 g/dl was arbitrarily chosen as cut-off value. RESULTS: In cases showing high basal HB status, the percentage of pathological response was significantly higher than in patients showing low HB status (76.3% versus 46.7%) (P value=0.027). When logistic regression was applied, only advanced stage remained associated with a poor chance of response to treatment. Cases with low basal HB status had a shorter DFS and OS than cases with a high HB status (P value=0.0001 and 0.0022, respectively). Similar results were obtained when analyzing nadir HB status. In multivariate analysis, high basal HB status, and advanced stage, retained an independent negative prognostic role for DFS and OS. CONCLUSIONS: Anemia identifies LACC patients administered preoperative radiochemotherapy, who are at higher risk of recurrence and death of disease.

Celecoxib up-regulates the expression of the zeta chain of T cell receptor complex in tumor-infiltrating lymphocytes in human cervical cancer.

PURPOSE: 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. EXPERIMENTAL DESIGN: 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. RESULTS: 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). CONCLUSIONS: 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.