Anna Fagotti

p53 Gene Status and Response to Platinum/Paclitaxel-Based Chemotherapy in Advanced Ovarian Carcinoma

PURPOSE The p53 gene plays a critical role in cellular response to DNA damage and has been implicated in the response to platinum compounds in ovarian carcinoma patients. Because taxanes could induce p53-independent apoptosis, we assessed the relevance of p53 gene status to response in ovarian carcinoma patients receiving paclitaxel and platinum-containing chemotherapy. PATIENTS AND METHODS Forty-eight previously untreated patients with advanced disease received standard paclitaxel/platinum-based chemotherapy. In tumor specimens collected at the time of initial surgery, before therapy, p53 gene status and expression were examined by single-strand conformation polymorphism, sequence analysis, and immunohistochemical analysis. Microsatellite instability analysis was performed on available samples from 30 patients. RESULTS Thirty-four (71%) of the 48 patients had a clinical response. Pathologic complete remission was documented in 13 (27%) of 48 patients. p53 mutations were detected in 29 (60%) of 48 tumors. Among the patients with mutant p53 tumors, 25 patients (86%) responded to chemotherapy. Only nine (47%) of 19 patients with wild-type p53 tumors responded to the same treatment. The overall response rate and the complete remission rate were significantly higher among patients with mutant p53 tumors than among patients with wild-type p53 tumors (P: =.008). Most of the tested tumors not associated with complete remission (10 of 12 tumors) were also characterized by microsatellite instability. The complete remission rate was higher among patients with tumors without microsatellite instability (five of seven patients). CONCLUSION In contrast to the limited efficacy of treatment with paclitaxel in combination with standard platinum doses against wild-type p53 ovarian tumors, patients with mutant p53 ovarian tumors were more responsive to paclitaxel-based chemotherapy. The pattern of response to chemotherapy containing paclitaxel is different from that associated with high-dose cisplatin therapy. Determining p53 mutational status can be useful in predicting therapeutic response to drugs effective in ovarian carcinoma.

A Laparoscopy-Based Score To Predict Surgical Outcome in Patients With Advanced Ovarian Carcinoma: A Pilot Study

BackgroundOur objective was to set up a more objective quantitative laparoscopy-based model in predicting the chances of optimal cytoreductive surgery in advanced ovarian cancer patients.MethodsSixty-four advanced ovarian cancer patients were submitted to both laparoscopy and standard longitudinal laparotomy sequentially, to define the chances of optimal debulking surgery (residual disease ≤1 cm). Three patients could not be evaluated by laparoscopy because of the presence of multiple and tenacious adherences. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were calculated for each laparoscopic parameter. On the basis of the statistical probability of each factor to predict surgical outcome, seven laparoscopic features were selected for inclusion in the final model. Each parameter was assigned a numerical score based on the strength of statistical association, and a total predictive index value was tabulated for each patient. Receiver operating characteristic curve analysis was used to assess the ability of the model to predict surgical outcome.ResultsAfter debulking surgery, 41 (67.2%) of 61 patients were left with optimal residual disease. The presence of omental cake, peritoneal carcinosis, diaphragmatic carcinosis, mesenteric retraction, bowel and/or stomach infiltration, and liver metastases satisfied the basic inclusion criteria and were assigned a final predictive index value of 2. In the final model, a predictive index score ≥8 identified patients undergoing suboptimal surgery with a specificity of 100%. The positive predictive value was 100%, and the negative predictive value was 70%.ConclusionsThe reliability of laparoscopy in assessing the chance of optimal cytoreduction can be improved by using a simple scoring system.

Postoperative pain after conventional laparoscopy and laparoendoscopic single site surgery (LESS) for benign adnexal disease: a randomized trial

OBJECTIVE To compare postoperative pain after laparoendoscopic single-site surgery (LESS) approach with conventional multiaccess laparoscopy (LPS). STUDY DESIGN Prospective randomized trial. SETTING University hospital. PATIENT(S) Benign adnexal disease. INTERVENTION(S) Postoperative pain was measured by using the visual analog scale (VAS) at 20 minutes, 2 hours, 4 hours, and 8 hours after surgery. The need for postoperative rescue doses of analgesia was also recorded. MAIN OUTCOME MEASURE(S) Pain after surgery. RESULT(S) A total of 60 patients were enrolled. Within 8 hours, patients who underwent conventional LPS complained of statistically significant greater postoperative pain at VAS evaluation than those undergoing LESS, both at rest and after Valsalva maneuver, with a higher need for rescue analgesia. CONCLUSION(S) LESS provides an advantage over conventional multiaccess LPS in terms of postoperative pain and need for rescue analgesia, with similar perioperative outcomes.

Prospective validation of a laparoscopic predictive model for optimal cytoreduction in advanced ovarian carcinoma

OBJECTIVE The purpose of this study was to validate the performance of a laparoscopy-based model to predict optimal cytoreduction in advanced ovarian cancer patients. STUDY DESIGN In a consecutive prospective series of 113 advanced ovarian cancer patients, the presence of omental cake, peritoneal and diaphragmatic extensive carcinosis, mesenteric retraction, bowel and stomach infiltration, spleen and/or liver superficial metastasis were investigated by laparoscopy. By summing the scores relative to all parameters, a laparoscopic assessment for each patient (total predictive index value = PIV) has been calculated. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy have been calculated for each PIV. RESULTS The overall accuracy rate of the laparoscopic procedure ranged between 77.3 and 100%. At a PIV >/= 8 the probability of optimally resecting the disease at laparotomy is equal to 0, and the rate of unnecessary exploratory laparotomy is 40.5%. CONCLUSION The proposed laparoscopic model appears a reliable and flexible tool to predict optimal cytoreduction in advanced ovarian cancer.

Laparoscopic Colorectal Resection for Bowel Endometriosis: Feasibility, Complications, and Clinical Outcome

OBJECTIVE To evaluate the short- and long-term outcomes of laparoscopic colorectal resection for endometriosis. DESIGN AND PATIENTS This study included 357 consecutive patients who underwent colorectal resection. We evaluated intraoperative and postoperative complications, symptom outcomes, and long-term follow-up. MAIN OUTCOME MEASURE Three hundred forty-three patients (96.1%) underwent laparoscopic colorectal resection, and radical endometriosis ablation was in 334 patients (93.6%). RESULTS Fourteen (3.9%) required laparoconversion. Median operating time was 300 (range, 85-720) minutes, with a median estimated blood loss of 250 (range, 50-550) mL. Radical endometriosis ablation was achieved in 334 patients (93.6%). Median ileus was 4 (range, 1-8) days, with a median postoperative hospitalization of 8 (range, 3-36) days. Early and late complications were observed in 44 patients (12.3%) and, in 35 of these (79.5%), surgical management was necessary. Median follow-up after colorectal resection was 19.6 (range, 6-48) months. The median preoperative and postoperative dyspareunia scores were 8 (range, 4-10) and 3 (range, 0-10), respectively (P < .04), and the median preoperative and postoperative gastrointestinal tract symptom scores were 7 (range, 2-10) and 2 (range, 0-10), respectively (P < .05). During follow-up, 24 of 286 recurrences (8.4%) were registered. Patients who previously underwent surgery for endometriosis showed a higher risk of recurrence compared with patients undergoing primary surgery (13.2% vs 3.4%; P < .048). CONCLUSIONS Laparoscopic colorectal resection for severe endometriosis is feasible and markedly improved endometriosis-related symptoms. Despite the risk of major postoperative complications, the procedure shows good results in terms of recurrence rate and could be adopted as the primary approach for patients with symptomatic colorectal infiltrating endometriosis.

Epidermal growth factor, oestrogen and progesterone receptor expression in primary ovarian cancer: correlation with clinical outcome and response to chemotherapy

The expression of epidermal growth factor receptor (EGFR), oestrogen receptor (ER) and progesterone receptor (PR) was assayed by a radioreceptor method in 117 primary ovarian cancers. EGFR was not significantly related to any of the clinicopathological parameters examined. In patients with stage II-IV disease who underwent second-look surgery after primary chemotherapy, a significant correlation between high EGFR levels and poor response to chemotherapy was demonstrated (P = 0.031). Moreover, post-operative residual tumour showed an independent role in predicting chemotherapy response (P = 0.0007) and EGFR status showed a borderline significance (P = 0.052) in the multivariate analysis. No correlation between steroid hormone receptors and clinicopathological parameters was observed. Whereas a significant relationship was shown between EGFR positivity and a shorter overall survival (OS) (P = 0.0022) and progression-free survival (PFS) (P = 0.0033), patient survival was not related to steroid hormone receptor status. Among the parameters tested only stage, ascites and EGFR status retained an independent prognostic value in the multivariate analysis.

Discoid or segmental rectosigmoid resection for deep infiltrating endometriosis: a case-control study

OBJECTIVE To evaluate the efficacy of discoid resection for the treatment of deep infiltrating endometriosis and whether it could be considered to be a valid alternative to the rectosigmoid segmental resection. DESIGN Case-control study. SETTING Departments of Obstetrics and Gynecology, Ospedale Sacro Cuore of Negrar, Verona, and Catholic University of the Sacred Heart, Rome, Italy. PATIENT(S) Women with deep infiltrating and intestinal endometriosis divided into study group (48 patients) and control group (88 patients). INTERVENTION(S) All patients underwent laparoscopic endometriosis excision plus discoid rectosigmoid resection (study group) or segmental resection (control group). MAIN OUTCOME MEASURE(S) Short- and long-term outcomes. RESULT(S) In the study group, median operating time was 200 minutes, with a median estimated blood loss of 203 mL. Median ileus was 3 days with a median postoperative hospitalization of 7 days. Early complications were observed in six patients (12.5%), and in two of them (4.16%) a surgical management was necessary. Median follow-up period was 33 months, and five recurrences (10.4%) were registered. In the control group, no significant differences were noticed except for longer operative time, more temporary ileostomy, postoperative fever, and long-term bladder dysfunctions. CONCLUSION(S) Laparoscopic mechanical discoid resection is feasible, markedly improved endometriosis related symptoms, and could be considered as a worthy alternative to classic segmental resection in selected patients.

Long-term analysis of clinical outcome and complications in locally advanced cervical cancer patients administered concomitant chemoradiation followed by radical surgery

OBJECTIVE Preoperative chemoradiation (CT/RT) has been shown to achieve encouraging results in terms of clinical outcome in locally advanced cervical cancer (LACC). The study aims at analyzing the long-term results of this multimodal approach in a single institution series of 184 cases. METHODS Patients underwent whole pelvic irradiation combined with cisplatin and 5-fluorouracil. After evaluation of clinical response, patients were triaged to surgery. Surgical morbidity was classified according to Chassagne grading system. Univariate and multivariate analyses were used to assess the prognostic and predictive role of clinicopathological parameters. RESULTS Clinical response was observed in 96.1% of cases. A total of 174 cases were submitted to radical surgery: 124 patients (71.3%) showed complete/microscopic pathological response. In multivariate analysis, clinical response, stage of disease, and histotype predicted response to CT/RT. With a median follow-up of 58 months, recurrence and death of disease were observed in 42 and 40 patients, respectively. The 5-year DFS was 75.5%, while the 5-year OS was 77.4%. Patients with no residual disease showed a significant longer DFS than patients with microscopic (p value = 0.0128), and macroscopic (p value = 0.0001) residual tumor after treatment. In multivariate analysis, residual tumor and stage of disease were the two most relevant prognostic factors for DFS and OS. As far as long-term toxicity is concerned, 8 out of 22 complications were grade 3/4. CONCLUSION Preoperative CT/RT is worth further investigation in LACC patients, providing encouraging survival outcomes and a favourable long-term toxicity profile.

Laparoendoscopic single-site surgery (LESS) for ovarian cyst enucleation: report of first 3 cases

OBJECTIVE To report the feasibility of ovarian cyst enucleation by using a laparoendoscopic single-site trocar through a transumbilical access. DESIGN Case reports. SETTING Teaching and research hospital. PATIENT(S) Three patients affected by large ovarian cysts. INTERVENTION(S) Enucleation of three large ovarian cysts by using a laparoendoscopic single-site approach with a new multiport trocar and standard laparoscopic instruments. MAIN OUTCOME MEASURE(S) Conversion to a multiaccess standard laparoscopic technique. RESULT(S) No conversion to multiaccess standard laparoscopic technique and no intraoperative or postoperative complications were observed. Mean operative time was 79.6 minutes. All patients were discharged home on day 1. CONCLUSION(S) Laparoendoscopic single-site enucleation of large ovarian cysts with ovary sparing is feasible with standard laparoscopic instruments, safe and effective, with good results in terms of cosmesis and postoperative pain. More clinical data are needed to confirm these advantages compared with standard laparoscopic technique.

Ecology: The proximate cause of frog declines?

Arising from: J. A. Pounds et al. 439, 161–167 (2006)10.1038/nature04246; Pounds et al. replyPounds et al. argue that global warming contributes to amphibian declines by encouraging outbreaks of the chytrid fungus Batrachochytrium dendrobatidis. Although our findings agree with the climate-linked epidemic hypothesis, this pathogen is probably not the only proximate factor in such cases: in the Trasimeno Lake area of Umbria in central Italy, for example, the water frog Rana lessonae first declined in the late 1990s, yet chytridiomycosis was not observed until 2003 (refs 5, 6). Here we show that the chytrid was common there throughout 1999–2002, in a previously unknown form that did not cause disease. We therefore think that the focus by Pounds et al. on a single pathogen is hard to justify because the host–parasite ecology is at present so poorly understood.