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Purpose: Overexpression of h III tubulin has been involved in paclitaxel resistance in several experimental models. We investigated the role of h III tubulin as predictor of clinical outcome in ovarian cancer patients given platinum/paclitaxel treatment. We also investigated whether h 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 h-tubulin antibody. Results: h III Tubulin immunoreaction was observed in 51 of 62 (82.2%) cases. h III Tubulin positivity was neither associated with clinicopathologic variables nor with pathologic response to chemotherapy. Significantly lower percentages of h 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 h III tubulin expression showed a worse overall survival with respect to cases with low h III tubulin expression (median overall survival, 25 versus 46 months; P = 0.002). Multivariate analysis showed that high content of h III tubulin remains independently associated with a worse prognosis. Conclusions: Assessment of h III tubulin could be useful to identify poor prognosis ovarian cancer patients candidates to more aggressive and/or targeted therapy.

ObjectiveTo investigate whether neoadjuvant chemotherapy followed by interval debulking surgery is superior to primary debulking surgery in terms of perioperative complications and progression-free survival, in advanced epithelial ovarian, fallopian tube or primary peritoneal cancer patients with high tumor load.MethodsPatients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer (stage IIIC-IV) underwent laparoscopy. Patients with high tumor load assessed by a standardized laparoscopic predictive index were randomly assigned (1:1 ratio) to undergo either primary debulking surgery followed by adjuvant chemotherapy (arm A), or neoadjuvant chemotherapy followed by interval debulking surgery and adjuvant chemotherapy (arm B). Co-primary outcome measures were progression-free survival and post-operative complications; secondary outcomes were overall survival, and quality of life. Survival analyses were performed on an intention-to-treat population.Results171 patients were randomly assigned to primary debulking surgery (n=84) versus neoadjuvant chemotherapy (n=87). Rates of complete resection (R0) were different between the arms (47.6% in arm A vs 77.0% in arm B; p=0.001). 53 major postoperative complications were registered, mainly distributed in arm A compared with arm B (25.9% vs 7.6%; p=0.0001). All patients were included in the intent-to-treat analysis. With an overall median follow-up of 59 months (95% CI 53 to 64), 142 (83.0%) disease progressions/recurrences and 103 deaths (60.2%) occurred. Median progression-free and overall survival were 15 and 41 months for patients assigned to primary debulking surgery, compared with 14 and 43 months for patients assigned to neoadjuvant chemotherapy, respectively (HR 1.05, 95% CI 0.77 to 1.44, p=0.73; HR 1.12, 95% CI 0.76 to 1.65, p=0.56).ConclusionsNeoadjuvant chemotherapy and primary debulking surgery have the same efficacy when used at their maximal possibilities, but the toxicity profile is different.

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Our study confirmed that minimally invasive surgery (laparoscopy or robotics) was as adequate and effective as abdominal surgery in terms of surgical and oncological outcomes in the surgical treatment of EEC FIGO stage IB1.

Background: Airway closure causes lack of communication between proximal airways and alveoli, making tidal inflation start only after a critical airway opening pressure is overcome. The authors conducted a matched cohort study to report the existence of this phenomenon among obese patients undergoing general anesthesia.Methods: Within the procedures of a clinical trial during gynecological surgery, obese patients underwent respiratory/lung mechanics and lung volume assessment both before and after pneumoperitoneum, in the supine and Trendelenburg positions, respectively. Among patients included in this study, those exhibiting airway closure were compared to a control group of subjects enrolled in the same trial and matched in 1:1 ratio according to body mass index.results: Eleven of 50 patients (22%) showed airway closure after intubation, with a median (interquartile range) airway opening pressure of 9 cm H 2 O (6 to 12). With pneumoperitoneum, airway opening pressure increased up to 21 cm H 2 O (19 to 28) and end-expiratory lung volume remained unchanged (1,294 ml [1,154 to 1,363] vs. 1,160 ml [1,118 to 1,256], P = 0.155), because end-expiratory alveolar pressure increased consistently with airway opening pressure and counterbalanced pneumoperitoneum-induced increases in end-expiratory esophageal pressure (16 cm H 2 O [15 to 19] vs. 27 cm H 2 O [23 to 30], P = 0.005). Conversely, matched control subjects experienced a statistically significant greater reduction in end-expiratory lung volume due to pneumoperitoneum (1,113 ml [1,040 to 1,577] vs. 1,000 ml [821 to 1,061], P = 0.006). With airway closure, static/dynamic mechanics failed to measure actual lung/respiratory mechanics. When patients with airway closure underwent pressure-controlled ventilation, no tidal volume was inflated until inspiratory pressure overcame airway opening pressure.conclusions: In obese patients, complete airway closure is frequent during anesthesia and is worsened by Trendelenburg pneumoperitoneum, which increases airway opening pressure and alveolar pressure: besides preventing alveolar derecruitment, this yields misinterpretation of respiratory mechanics and generates a pressure threshold to inflate the lung that can reach high values, spreading concerns on the safety of pressure-controlled modes in this setting.

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 ¼ 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 ¼ 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. (Hoskins et al, 2000), it is conceivable that the assessment of biochemical factors more strictly related to tumour cell biology and intrinsic aggressiveness could help identifying high-risk patients and facilitating management of this disease.Apoptosis (programmed cell death) has been proposed to play a role not only in cancer onset and progression but also in sustaining decreased tumour cell sensitivity to chemotherapy (Hickman, 1992;Thompson, 1995), which still represents one of the main prognostic indicators in this neoplasia (Hoskins et al, 2000). In this context, the analysis of the molecules possibly involved in the modulation of apoptosis seems to be particularly attractive.Survivin is a member of the inhibitors of apoptosis protein (IAP) family, which participates in the complex network regulating programmed cell death and also cell division (Ambrosini et al, 1997;Altieri and Marchisio, 1999;Salvesen and Duckett, 2002). Survivin protein is commonly detected in fetal tissues but not in normal adult tissues, while being overexpressed in human cancer, thus suggesting the contribution of survivin gene reactivation in carcinogenesis (Ambrosini et al, 1997). The crucial role of survivin in protection from apoptosis is supported by the o...