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Objectives To evaluate the role of cervical re-injection of indocyanine green (ICG) to increase the detection rate of sentinel lymph node (SLN) in patients with endometrial cancer (EC) who underwent robotic-assisted surgical staging. Methods We retrospectively identified consecutive EC patients undergoing robotic-assisted staging with SLN biopsy at our Institution between June 2016 and April 2020. Patients were excluded if they had open abdominal surgical approach, neoadjuvant chemotherapy, and advanced stage [International Federation of Gynecology and Obstetrics (FIGO) stage III-IV] at diagnosis. According to our SLN protocol, in case of either unilateral or no SLN detection, we performed an ipsilateral or bilateral cervical re-injection of ICG. Results In total, 251 patients meeting inclusion criteria were included in the analysis. At first injection, bilateral detection was achieved in 184 (73.3%), unilateral detection in 57 (22.7%), and no detection in 10 (4.0%) patients. Cervical re-injection was performed in 51 of 67 patients with failed bilateral mapping. After cervical re-injection, bilateral detection rate increased to 94.5% (222/235), while unilateral and no detection were 5.1% (12/235) and 0.4% (1/235), respectively. Conclusions Our results suggest that cervical re-injection of ICG, in case of failed bilateral mapping of SLN, brings about a significant improvement in SLN detection rates, therefore reducing the number of side-specific required lymphadenectomies.

BACKGROUND: Treatment for patients with recurrent ovarian cancer has been mainly based on systemic therapy. The role of secondary cytoreductive surgery is unclear. METHODS: We randomly assigned patients with recurrent ovarian cancer who had a first relapse after a platinum-free interval (an interval during which no platinum-based chemotherapy was used) of 6 months or more to undergo secondary cytoreductive surgery and then receive platinum-based chemotherapy or to receive platinum-based chemotherapy alone. Patients were eligible if they presented with a positive Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) score, defined as an Eastern Cooperative Oncology Group performance-status score of 0 (on a 5-point scale, with higher scores indicating greater disability), ascites of less than 500 ml, and complete resection at initial surgery. A positive AGO score is used to identify patients in whom a complete resection might be achieved. The primary end point was overall survival. We also assessed quality of life and prognostic factors for survival. RESULTS: A total of 407 patients underwent randomization: 206 were assigned to cytoreductive surgery and chemotherapy, and 201 to chemotherapy alone. A complete resection was achieved in 75.5% of the patients in the surgery group who underwent the procedure. The median overall survival was 53.7 months in the surgery group and 46.0 months in the no-surgery group (hazard ratio for death, 0.75; 95% confidence interval, 0.59 to 0.96; P = 0.02). Patients with a complete resection had the most favorable outcome, with a median overall survival of 61.9 months. A benefit from surgery was seen in all analyses in subgroups according to prognostic factors. Quality-of-life measures through 1 year of follow-up did not differ between the two groups, and we observed no perioperative mortality within 30 days after surgery. CONCLUSIONS: In women with recurrent ovarian cancer, cytoreductive surgery followed by chemotherapy resulted in longer overall survival than chemotherapy alone. (Funded by the AGO Study Group and others; DESKTOP III ClinicalTrials.gov number, NCT01166737.).

Introduction: Ovarian cancer is the most lethal gynecologic malignancy. Over 5200 new cases of this tumor are diagnosed yearly in Italy, resulting in more than 3600 deaths. In terms of molecular biology, five different ovarian cancer subtypes should be distinguished. Method: This article summarizes the evidence-based guidelines that the Italian Medical Oncology Association (AIOM) has developed with a multidisciplinary panel of experts, including pathologists, gynecologic oncologists, medical oncologists, and radiotherapists, with the support of methodologists, to help clinicians involved in the management of patients with ovarian cancer in their daily clinical practice. Results: The most relevant randomized clinical trials regarding surgery, chemotherapy, and molecularly targeted agents (bevacizumab and PARP inhibitors) in early, advanced, and recurrent disease have been critically analyzed. The levels of evidence and strength of recommendation have been reported for any issue. Conclusion: Women with a clinical suspicion of ovarian cancer should be centralized in referral centers. The BRCA test should be requested for all women with nonmucinous and nonborderline tumors, regardless of age and family history. BRCA testing could be preferentially performed on neoplastic tissue. In the presence of a positive tumor test, a genetic test should always be performed on a blood sample to differentiate between germline mutations, which require counseling and genetic testing of family members, and somatic mutations.

ObjectiveThe role of adjuvant chemotherapy as an addition or alternative to radiotherapy for early-stage high-risk endometrioid endometrial cancer is controversial. This study aimed to investigate the role of adjuvant chemotherapy in early-stage high-risk endometrioid endometrial cancer.MethodsWe identified patients with stage I or II endometrioid grade 2 or 3 endometrial cancer with myometrial invasion >50% and negative lymph nodes after pelvic with or without para-aortic lymphadenectomy at four institutions (USA and Italy). Associations between chemotherapy and cause-specific and recurrence-free survival were assessed with Cox proportional hazards models. Hematogenous, peritoneal, and lymphatic recurrences were defined as 'non-vaginal'.ResultsWe identified 329 patients of mean (SD) age 66.4 (9.8) years. The median follow-up among those alive was 84 (IQR 44–133) months. The 5-year cause-specific survival was 86.1% (95% CI 82.0% to 90.4%) and the 5-year recurrence-free survival was 82.2% (95% CI 77.9% to 86.8%). Stage II (vs stage IB) was associated with poorer cause-specific and recurrence-free survival. A total of 58 (90.6%) of 64 patients who had chemotherapy had 4–6 cycles of platinum-based regimen. In adjusted analysis, we did not observe a statistically significant improvement in cause-specific survival (HR 0.34; 95% CI 0.11 to 1.03; p=0.06) or non-vaginal recurrence-free survival (HR 0.36; 95% CI 0.12 to 1.08; p=0.07) with adjuvant chemotherapy. Sixteen of 18 lymphatic recurrences (88.9%; 3/5 pelvic, all 13 para-aortic) were observed in the 265 patients who did not receive adjuvant chemotherapy. Among stage II patients, no deaths (100% 5-year recurrence-free survival) were observed in the eight patients who received adjuvant chemotherapy compared with 66% 5-year recurrence-free survival in the 34 patients who did not.ConclusionAlthough we observed that adjuvant chemotherapy was associated with improved oncologic outcomes in early-stage high-risk endometrioid endometrial cancer, the associations did not meet conventional levels of statistical significance. Further research is warranted in this relatively uncommon subgroup of patients.

Objective advanced stage clear cell ovarian cancer (CCOC) carries a higher risk of relapse and death compared to other histological subtypes. The prognosis of early-stage CCOC is controversial. Methods Early-stage high-grade OC patients from two Italian oncologic centers were included. Patients with early-stage CCOC were compared with those with high-grade endometrioid (HGE) and serous (HGS) OC in terms of relapse-free interval (RFI), cancer-specific survival (CSS) and post relapse cancer-specific survival (prCSS). The Cox proportional hazard model and the restricted mean survival time were used. Results Between 1981 and 2012, 134 patients with CC, 152 with HGE and 160 with HGS were treated at two referral centers. Median follow-up was 11.5 years. Ten years RFI rates were 80.6%, 72.1%, 60.6%, and CSS rates were 84.3%, 82.6%, 81.7% respectively. Adjuvant chemotherapy significantly improved RFI (aHR 0.61, 95%CI 0.40 to 0.91, P = 0.015). In the multivariable analysis HGS histotype was associated with a shorter RFI compared to CC, (Hazard Ratio [HR]: 1.81; 95%CI: 1.12–2.93; P = 0.016), whereas CSS was not statistically different. prCSS was longer in HGS compared to CCOC (HR, 0.36; 95% CI, 0.17–0.74; P = 0.006). According to the stage, IA/IB/IC1 HGSOC had a shorter RFI (HR, 2.13; 95% CI, 1.14–3.99; P = 0.018) compared to IA/IB/IC1 CCOC, but similar CSS. For prCSS, CC compared to HGS conferred a worse prognosis regardless of the initial stage. Conclusions Early-stage CCOC is associated with a longer RFI, similar CSS and a shorter prCSS compared to HGSOC. No prognostic differences were observed between CC and HGE OC. The relapse risk was the lowest in IA/IB/IC1 CC compared to HGS, whereas CC displayed poor sensitivity to chemotherapy after relapse.

ObjectivesAdult primary cervical rhabdomyosarcoma is a very rare disease and data regarding treatment are sparce. The goal of this study was to report on our experience with the management of this rare entity, along with an evaluation of the literature.MethodsWe conducted a review of the medical records at four centers from January 1990 to December 2017. We reviewed clinical characteristics including age at diagnosis, BMI, medical history and tumor stage, as well as treatment in the primary and recurrent settings and follow-up data. We reclassified tumors according to the Intergroup Rhabdomyosarcoma Study (IRS) clinical group.ResultsA total of 15 patients were included in the analysis. Median age at diagnosis was 35 years (range 17–55). Median tumor size at presentation was 5 cm (range 3–10). Eleven patients had the embryonal variant, including five showing the botryoid subtype. Four patients had a pleomorphic rhabdomyosarcoma. Eleven patients had disease classified as IRS Clinical Group I, while the remaining four fell into groups II or III. Fertility-sparing treatment was offered to five patients. Primary treatment types were: surgery alone in eight patients, surgery followed by adjuvant chemotherapy in six patients, and neoadjuvant chemotherapy in two patients. The main risk factors for relapse were: IRS clinical group greater than I, tumor size greater than 5 cm, lymph nodal involvement, and non-embryonal histology. At a median follow-up of 35 months (range 3–282), we observed a 5-year overall survival rate of 78.2% and a progression-free survival of 58.2%. No patient in the IRS I group died of the disease. Three out of four patients in the IRS II-III group died of the disease (survival range 5–16 months following treatment).ConclusionOur data show that cervical rhabdomyosarcomas account for at least two prognostic groups, demonstrating the existence of low-risk and high-risk patterns. The best predictor of prognosis appearsd to be the IRS clinical group classification system. IRS Group I tumors had an overall good prognosis and rarely recurred; when they did recur they were mainly local, following conservative treatment.

To determine if radiomic features, alone or combined with clinical data, are associated with residual tumour (RT) at surgery, and predict the risk of disease progression within 12 months (PD12) in ovarian cancer (OC) patients. This retrospective study enrolled 101 patients according to the following inclusion parameters: cytoreductive surgery performed at our institution (9 May 2007–23 February 2016), assessment of BRCA mutational status, preoperative CT available. Radiomic features of the ovarian masses were extracted from 3D structures drawn on CT images. A phantom experiment was performed to assess the reproducibility of radiomic features. The final radiomic features included in the analysis (n = 516) were grouped into clusters using a hierarchical clustering procedure. The association of each cluster’s representative radiomic feature with RT and PD12 was assessed by chi-square test. Multivariate analysis was performed using logistic regression models. P values < 0.05 were considered significant. Patients with values of F2-Shape/Compactness1 below the median, of F1- GrayLevelCooccurenceMatrix25/0-1InformationMeasureCorr2 below the median and of F1-GrayLevelCooccurenceMatrix25/-333-1InverseVariance above the median showed higher risk of RT (36%, 36% and 35%, respectively, as opposed to 18%, 18% and 18%). Patients with values of F4-GrayLevelRunLengthMatrix25/-333RunPercentage above the median, of F2 shape/Max3DDiameter below the median and F1-GrayLevelCooccurenceMatrix25/45-1InverseVariance above the median showed higher risk of PD12 (22%, 24% and 23%, respectively, as opposed to 6%, 5% and 6%). At multivariate analysis F2-Shape/Max3DDiameter remained significant (odds ratio (95% CI) = 11.86 (1.41–99.88)). To predict PD12, a clinical radiomics model performed better than a base clinical model. This study demonstrated significant associations between radiomic features and prognostic factors such as RT and PD12. • No residual tumour (RT) at surgery is the most important prognostic factor in OC. • Radiomic features related to mass size, randomness and homogeneity were associated with RT. • Progression of disease within 12 months (PD12) indicates worse prognosis in OC. • A model including clinical and radiomic features performed better than only-clinical model to predict PD12.

ObjectivesThe purpose of this retrospective report is to define the safety and feasibility, based on our preliminary experience, of surgical transdiaphragmatic resection of enlarged cardiophrenic lymph nodes (CPLNs), as a part of upfront debulking surgery. Supradiaphragmatic nodes located between the diaphragm and the heart are frequently a location for lymph node metastasis in advanced ovarian cancer, and their removal is aimed to obtain no gross residual disease at the primary cytoreductive surgery often requiring aggressive surgical procedures.Patients and MethodsBetween May 2012 and October 2016, a total of 22 patients among 443 with advanced high-grade serous ovarian cancer underwent cytoreductive procedures involving transdiaphragmatic resection of enlarged CPLNs at European Institute of Oncology in Milan.ResultsAll patients who underwent CPLN resection had an extensive disease (median peritoneal cancer index, 18), and more than 77% required complex surgical procedures (complexity score, 3). No residual abdominal disease less than 5 mm at the end of surgery was described in 20 (90%) out of 22. All patients but one had confirmed CPLN positive nodes at histopathological study. The average operative time was 333 min (range, 244–455 min), and the average estimated blood loss was 1000 mL (range, 400–2000 mL). Blood transfusion was necessary in 13 out of 22 patients. Only 7 (33%) out of 21 patients required chest tube placement during the postoperative period.ConclusionsTransdiaphragmatic enlarged CPLN resection seems to be safe and feasible procedure when indicated to achieve no or minimal tumor residual disease. Nevertheless, its impact on survival of patients with stage IV ovarian cancer needs to be determined.

Cervical sarcomas are rare neoplasms, accounting for

Background Inguinal field block (IFB) is a recommended technique for pain control after inguinal hernia repair but is also underused by surgeons. Currently, there is no decisive evidence on which technique, IFB or spinal anesthesia block (SAB), provides better pain control during the first day after hernia repair. In this study, we compared ultrasound-guided IFB performed by anesthesiologists and SAB for pain control during the first day after hernia repair. Methods We compared static and dynamic pain scores measured with a numerical rating scale in 86 male patients scheduled for elective unilateral inguinal hernia repair with either ultrasound-guided IFB (n = 42) or SAB (n = 44). Results Dynamic and static pain at 4 hours (P 0.34, “large effect size”), and dynamic pain the morning after operation (P = .04, r > 0.20, “medium effect size”) were less in the field block group compared with the SAB group. Postoperative analgesic consumption was reduced during hospital stay (P = .005, r > 0.34, “large effect size”) and for 7 postoperative days in the field block group (P = .03, r > 0.20, “medium effect size”). Conclusion In this study, ultrasound-guided IFB provided lesser dynamic pain scores during the first postoperative day and reduced use of analgesics for 1 week compared with spinal anesthesia after inguinal hernia repair. Our technique could become a substitute performed by anesthesiologists in settings in which IFB is not performed routinely by surgeons.

Background/aim Occult cancers' reported rates vary from 2-12% and serous tubal intraepithelial carcinomas (STICs) have been identified in 3-12% of the prophylactically removed tubes of women carrying a BRCA mutation. The aim of this study was to evaluate the incidence of tubal minor epithelial atypia (STIL), STIC, and occult invasive cancer and to evaluate the cancer-specific mortality in a prospective series of women at higher risk of ovarian and breast cancer undergoing risk-reducing salpingo-oophorectomy (RRSO) n a tertiary cancer center. Patients and methods A series of RRSO specimens (including endometrial biopsy) from women carrying a BRCA mutation, BRCA-unknown and BRCA-negative were collected between January 1998 and April 2016 at the Division of Gynecology at the European Institute of Oncology. Inclusion criteria were: asymptomatic women who had a negative gynecologic screening within 3 months prior to RRSO. Exclusion criteria were: women with ovarian/tubal cancer prior to RRSO. Results A total of 411 women underwent RRSO. Median age at RRSO was 47.0 years (range=32-70 years); 75.2% had a history of breast cancer. Fifteen women were diagnosed with an occult cancer (7 STIC, 4 invasive cancers, 2 breast cancers metastatic to the adnexa, 2 endometrial cancer) (3.6%). Sixteen showed a STIL (3.9%). When excluding cases with preoperative positive markers, the occult invasive cancer rate drops to 1.5%. Conclusion Our study, covering an 18-year period, shows a substantial low risk of occult cancer among a high-risk population of women undergoing RRSO. Our data still support the indication for RRSO in higher-risk patients. An endometrial biopsy should also be routinely obtained as it raises the chances of detecting occult endometrial cancers that may be otherwise missed.

Background Although widely adopted, the use of a uterine manipulator during laparoscopic treatment of endometrial cancer represents a debated issue, and some authors hypothesize that it potentially may cause an increased risk of relapse, particularly at specific sites. Objective Our aim was to evaluate the risk and site of disease recurrence, overall survival, and disease-specific survival in women who had laparoscopic surgery with and without the use of a uterine manipulator. Study Design Data were reviewed from consecutive patients who had laparoscopic surgery for endometrial cancer staging in 7 Italian centers. Subjects were stratified according to whether a uterine manipulator was used during surgery; if so, the type of manipulator was identified. Multivariable analysis to correct for possible confounders and propensity score that matched the minimize selection bias were utilized. The primary outcome was the risk of disease recurrence. Secondary outcomes were disease-specific and overall survival and the site of recurrence, according to the use or no use of the uterine manipulator and to the different types of manipulators used. Results We included 951 patients: 579 patients in the manipulator group and 372 patients in the no manipulator group. After a median follow-up period of 46 months (range,12–163 months), the rate of recurrence was 13.5% and 11.6% in the manipulator and no manipulator groups, respectively ( P =.37). Positive lymph nodes and myometrial invasion of >50% were associated independently with the risk of recurrence after adjustment for possible confounders. The use of a uterine manipulator did not affect the risk of recurrence, both at univariate (odds ratio, 1.18; 95% confidence interval, 0.80–1.77) and multivariable analysis (odds ratio, 1.00; 95% confidence interval, 0.60–1.70). Disease-free, disease-specific, and overall survivals were similar between groups. Propensity-matched analysis confirmed these findings. The site of recurrence was comparable between groups. In addition, the type of uterine manipulator and the presence or not of a balloon at the tip of the device were not associated significantly with the risk of recurrence. Conclusion The use of a uterine manipulator during laparoscopic surgery does not affect the risk of recurrence and has no impact on disease-specific or overall survival and on the site of recurrence in women affected by endometrial cancer.

Objective The aim of the present study was to evaluate the impact of a multidisciplinary approach in patients' selection with advanced ovarian cancer (AOC) for different therapeutic strategies. Methods Patients referred at our institution between 2009 and 2012 for AOC were included. Primary multidisciplinary evaluation was performed in all patients. Different strategies included: 1. patients referred to primary neoadjuvant chemotherapy (NACT) and interval surgery (IDS) (group A); 2. patients considered for surgical exploration. After surgical exploration, patients were either considered for primary debulking (PDS; group B), or NACT (group C). Results A total of 363 patients were included. Of 38 patients (10.5%) in group A, 24 (63%) had sovradiaphragmatic/multiple liver metastases; 14 (37%) were excluded for PDS for anestehesiologic/medical reasons. Of 325 (89.5%) considered for surgical exploration, 295 (91%; group B) had primary surgery with debulking intent (N: 277) and were cytoreduced to no macroscopic disease (R0: N:200; 68%) o minimal RD

Objectives To compare the clinical and oncologic outcomes of robotic radical hysterectomy (RRH) vs abdominal radical hysterectomy (ARH) in patients with cervical carcinoma. Methods A retrospective analysis of women who underwent radical hysterectomy for cervical cancer from December 2006 to December 2014 at European Institute of Oncology was performed. Patients who underwent RRH were compared with women operated on by ARH. The groups were matched by age, body mass index, tumor size, International Federation of Gynecology and Obstetrics stage, comorbidity, previous neoadjuvant chemotherapy, histology type, and tumor grade. Results A total of 203 and 104 women who underwent RRH and ARH, respectively, were analyzed. Baseline characteristics, stage of disease, histology type, and grade of differentiation were similar between groups. Surgical time was significantly shorter in the ARH group (208 vs 282 minutes, P ⩽ 0.001). Robotic radical hysterectomy was associated with significantly less estimated blood loss (219 vs 104 mL, P = 0.001) and with significantly shorter hospital stay (5.2 vs 3.9 days, P ⩽ 0.001). Abdominal radical hysterectomy was correlated with a significantly higher number of lymph nodes removed (25.8 vs 22, P = 0.003). None of the robotic procedures required conversion to laparotomy. A significantly higher number of patients in ARH required postoperative transfusion (11 [10.5%] vs 6 [2.9%], P = 0.006). Lower extremity lymphedema was significantly higher in ARH (28 [27.5%] vs 17 [8.3%], P = 0.001). Recurrence rates as well as progression-free survival and overall survival were similar between groups at a median follow-up of 41.64 months. Conclusions Robotic radical hysterectomy is safe and feasible and is associated with improved clinical outcomes. Although longer follow-up is needed, early data show equivalent oncologic outcomes compared with other surgical modalities.

Objective: Isoflurane is a volatile anesthetic that has a vasodilating effect on cerebral vessels producing a cerebral blood flow increase. Furthermore, it has been shown in animal studies that isoflurane, when used as a preconditioning agent, has neuroprotective properties, inducing tolerance to ischemia. However, it is not routinely used in neurointensive care because of the potential increase in intracranial pressure caused by the rise in cerebral blood flow. Nevertheless, subarachnoid hemorrhage patients who are at risk for vasospasm may benefit from an increase in cerebral blood flow. We measured regional cerebral blood flow during intravenous sedation with propofol and during sedation with isoflurane in patients with severe subarachnoid hemorrhage not having intracranial hypertension. Design: The study is a crossover, open clinical trial (NCT00830843). Setting: Neurointensive care unit of an academic hospital. Patients: Thirteen patients with severe subarachnoid hemorrhage , (median Fisher scale 4), monitored on clinical indication with intracranial pressure device and a thermal diffusion probe for the assessment of regional cerebral blood flow. An intracranial pressure >18 mm Hg was an exclusion criterion. Interventions: Cerebral and hemodynamic variables were assessed at three steps. Step 1: sedation with propofol 3–4 mg/ kg/hr; step 2: after 1 hr of propofol discontinuation and isoflurane 0.8%; step 3: after 1 hr of propofol at the same previous infusion rate. Cerebral perfusion pressure and arterial Pco 2 were maintained constant. Mean cerebral artery flow velocity and jugular vein oxygen saturation were measured at the end of each step. Measurements and Main Results: Regional cerebral blood flow increased significantly during step 2 (39.3 ± 29 mL/100 hg/min) compared to step 1 (20.8 ± 10.7) and step 3 (24.7 ± 8). There was no difference in regional cerebral blood flow comparing step 1 vs. step 3. No significant difference in intracranial pressure, mean cerebral artery transcranial Doppler velocity, PaCO 2 , cerebral perfusion pressure between the different steps. Conclusions: Isoflurane increases regional cerebral blood flow in comparison to propofol. Intracranial pressure did not change significantly in the population not affected by intracranial hypertension. (Crit Care Med 2012; 40:2797–2804)

Epithelial ovarian carcinoma (EOC) is an aggressive neoplasm, which mainly disseminates to organs of the peritoneal cavity, an event mediated by molecular mechanisms that remain elusive. Here, we investigated the expression and functional role of neural cell adhesion molecule (NCAM), a cell surface glycoprotein involved in brain development and plasticity, in EOC. NCAM is absent from normal ovarian epithelium but becomes highly expressed in a subset of human EOC, in which NCAM expression is associated with high tumour grade, suggesting a causal role in cancer aggressiveness. We demonstrate that NCAM stimulates EOC cell migration and invasion in vitro and promotes metastatic dissemination in mice. This pro-malignant function of NCAM is mediated by its interaction with fibroblast growth factor receptor (FGFR). Indeed, not only FGFR signalling is required for NCAM-induced EOC cell motility, but targeting the NCAM/FGFR interplay with a monoclonal antibody abolishes the metastatic dissemination of EOC in mice. Our results point to NCAM-mediated stimulation of FGFR as a novel mechanism underlying EOC malignancy and indicate that this interplay may represent a valuable therapeutic target. © 2011 EMBO Molecular Medicine.

Resistance to chemotherapy presents a serious challenge in the successful treatment of various cancers and is mainly responsible for mortality associated with disseminated cancers. Here we show that expression of HtrA1, which is frequently downregulated in ovarian cancer, influences tumor response to chemotherapy by modulating chemotherapy-induced cytotoxicity. Downregulation of HtrA1 attenuated cisplatin- and paclitaxel-induced cytotoxicity, while forced expression of HtrA1 enhanced cisplatin- and paclitaxel-induced cytotoxicity. HtrA1 expression was upregulated by both cisplatin and paclitaxel treatment. This upregulation resulted in limited autoproteolysis and activation of HtrA1. Active HtrA1 induces cell death in a serine protease-dependent manner. The potential role of HtrA1 as a predictive factor of clinical response to chemotherapy was assessed in both ovarian and gastric cancer patients receiving cisplatin-based regimens. Patients with ovarian or gastric tumors expressing higher levels of HtrA1 showed a higher response rate compared with those with lower levels of HtrA1 expression. These findings uncover what we believe to be a novel pathway by which serine protease HtrA1 mediates paclitaxel- and cisplatin-induced cytotoxicity and suggest that loss of HtrA1 in ovarian and gastric cancers may contribute to in vivo chemoresistance.

PURPOSE: To prospectively evaluate the accuracy of integrated positron emission tomography (PET) and computed tomography (CT) for depiction of persistent ovarian carcinoma after first-line treatment, with use of histologic findings as the reference standard. MATERIALS AND METHODS: Thirty-one women (mean age, 55.9 years) with ovarian carcinoma treated with primary cytoreductive surgery and followed up with platinum regimen chemotherapy were included. All 31 patients were scheduled for surgical second-look. Before surgical second-look, all patients underwent fluorodeoxy-glucose (FDG) PET/CT. At PET/CT, three main categories of persistent disease were considered for data analysis: lymph nodal lesion, peritoneal lesion, and pelvic lesion. In all patients, imaging findings were compared with results of histologic examination after surgical second-look to determine the diagnostic accuracy of PET/CT in the evaluation of disease status. The kappa statistic (Cohen kappa) was used for statistical analysis. RESULTS: Seventeen (55%) of 31 patients had persistent tumor at histologic analysis after surgical second-look, and fourteen (45%) had no histologically proved tumor. The total number of lesions that was positive for tumor cells at histologic analysis was 41 (lymph nodes, n = 16; peritoneal lesions, n = 21; pelvic lesions, n = 4); maximum diameter of these lesions was 0.3-3.2 cm (mean, 1.7 cm). A correlation was found between PET/CT and histologic analysis (kappa = 0.48). The overall lesion-based sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of PET/CT were 78%, 75%, 77%, 89% and 57%, respectively. In the detection of a tumor, a size threshold could be set at 0.5 cm, as this was the largest diameter of a lesion missed at PET/CT. CONCLUSION: Integrated PET/CT depicts persistent ovarian carcinoma with a high positive predictive value. (C) RSNA, 2004.

Objectives The aim of the study is to evaluate the response to neoadjuvant chemotherapy (NACHT) of patients with recurrent cervical cancer who were poor candidates for pelvic exenteration (PE), and the impact on DFS and OS. Methods A retrospective data collection extracted from medical records of 61 patients submitted to pelvic exenteration was performed: 30 underwent up-front exenterative procedure whereas 31 received NACHT. Results The median tumor size was significantly (P = 0.0006) larger in the NACHT group compared to the up-front PE one (43.9 mm vs 28 mm), and a significant (P = 0.04) higher percentage of patients (45 vs 20%) had lateral pelvic wall invasion in the NACHT group. No statistically significant difference in early and late complications was observed in the two groups. Median overall survival in study population was 42.9 months (95% CI: 22.2, 180.8). Median overall survival times as well as recurrence free survival times were not significantly different between NACHT (42.9 months and 36.1 months for OS and DFS respectively) vs. No NACHT (111.9 months and 48.1 months for OS and DFS respectively). There was an overall significant difference in DFS between negative and positive margins but the curves were similar for NACHT and up-front PE groups stratified by resection margin status. Conclusions In our series, though small and retrospective, NACHT prior to PE represents a feasible therapeutic option without intra-operative and early post-operative mortality or worsening of early and late complication rate and with acceptable long-term survival and DFS for recurrent cervical cancer patients who are poor candidates for up-front pelvic exenteration. © 2013 Elsevier Inc.

BackgroundThe aim of surgical approach in advanced ovarian cancer should be the complete removal of all visible disease. Our purpose was to compare perioperative features and postoperative complications, and secondarily oncological outcomes, between patients who underwent splenectomy and those who did not at the time of surgery.Materials and MethodsThirty-three subjects underwent splenectomy, and we selected 99 controls with similar surgical characteristics but who did not undergo splenectomy. Data collected included perioperative details and follow-up data.ResultsLonger operating time (33 minutes longer;P= 0.02), larger estimated blood loss (812 mL more;P= 0.03), higher rate of intraoperative blood transfusions (78.8% vs 42.4%;P< 0.01), and intensive care unit stay (1.4 vs 0.5 days;P< 0.01) as well as higher pneumonia rate (2% vs 0%;P= 0.01) were observed in the splenectomy group. Disease-free and overall survival rates were 30.3% and 66.6%, respectively, in the splenectomy group, and 33.3% and 59.6%, respectively, in the control group.ConclusionsSplenectomy at the time of primary cytoreductive surgery for advanced ovarian cancer may contribute to achieve complete cytoreduction with low perioperative complication rate. This procedure seems to be an acceptable and rational intervention to increase the survival rates of those patients.

Objective: The aim of the study was to determine the impact of rectosigmoid resection, at the time of primary cytoreductive surgery, on morbidity and survival of patients with advanced ovarian cancer. Methods: We performed a retrospective medical chart review of patients who underwent rectosigmoid resection for ovarian, tubal and peritoneal cancers between 1998 and 2008 at the IEO in Milan and JHMI in Baltimore. Perioperative and follow-up data were collected. Results: A total of 238 patients were identified; 180 (75%) had stages IIC-IIIC and 58 (25%) had stage IV. Complete cytoreduction was achieved in 41% of the cases. Stapled coloproctostomy was performed in 98% while hand sewn in only 2%; a protective ileostomy and colostomy were necessary (constructed) in 2 (0.8%) and 5 (2%) cases respectively. The complications associated to rectosigmoid resection were anastomotic leakage in 7 (3%) patients and pelvic abscess in 9 (3.7%). Fifty percent of patients recurred during the study period, but only 5% of them showed a relapse at the level of the pelvis whereas 8% presented with abdominal recurrence associated with pelvic disease as well. The median overall survival time among patients with complete cytoreduction was 72 months compared with 42 months among the rest of patients (p = 0.002). Conclusions: Rectosigmoid colectomy may significantly contribute to achieve a complete primary cytoreduction for advanced stage ovarian, tubal and peritoneal cancers. Pelvic complete debulking accomplished by rectosigmoid resection could be associated with a lower rate of pelvic recurrence as well. © 2012 Elsevier Inc. All rights reserved.

BackgroundStandard approach for medically stable advanced ovarian cancer patients should be primary cytoreduction following platinum-based chemotherapy. The aim of surgical effort should be the complete removal of all visible disease. Our objective was to compare perioperative features, postoperative complications, and secondarily oncological outcomes of patients who underwent diaphragmatic stripping with those who underwent diaphragmatic resection for advanced ovarian cancer.MethodsOne hundred twelve cases were identified, among them 79 underwent diaphragmatic stripping and 33 underwent diaphragmatic full-thickness resection. Data collected included patients’ age, all perioperative details and pathological findings, International Federation of Gynecology and Obstetrics stage, adjuvant therapy, and follow-up data.ResultsLarger residual tumors (mean, 5.1 vs 1.6 mm, respectively;P< 0.01) but shorter operating time (25 minutes shorter operative time,P= 0.07) were observed in the stripping group. Higher postoperative pleural effusions rates (63.6% vs 37.9%,P= 0.01), but no differences in the remaining complications, were observed in the resection group. After a mean of 31 months of follow-up, disease-free survival rates were 27.8% in the stripping group and 39.4% in the resection group (P= 0.04). No significant differences were observed for overall survival.ConclusionsDiaphragmatic surgery at the time of primary cytoreductive surgery for advanced ovarian cancer may contribute to the achievement of complete cytoreduction with low perioperative complication rate; full-thickness resection is preferable if peritoneum stripping will not achieve a complete removal of the disease.

Objective To determinate the impact of maximal cytoreductive surgery on progression free survival (PFS), overall survival (OS) rates and morbidity, in patients with advanced epithelial ovarian or fallopian tube cancer. Methods We reviewed all medical records of patients with stages IIIC–IV epithelial ovarian and fallopian tube cancer that were managed at our institution between January 2001 and December 2008. The following information was collected: demographics, tumor characteristics, operative information, surgical outcomes and peri-operative complication. Results A total of 288 patients with advanced epithelial ovarian and fallopian tube cancer were referred to our institution between January 2001 and December 2008, 259 consecutive patients were enrolled in the study. After a median follow-up of 29.8 months, the PFS and OS were 19.9 and 57.6 months, respectively. At univariate analysis, factors significantly associated with decreased PFS included: age greater than median (> 60 years), stage IV, presence of ascites > 1000 cc, presence of diffuse peritoneal carcinomatosis and diameter of residual disease. This was confirmed also at multivariate analysis with age greater than 60 years (P = 0.025), stage IV vs IIIC (P = 0.037) and any residual disease (P = 0.032) having an independent association with worse PFS. Conclusions Our study seems to demonstrate that a more extensive surgical approach is associated with prolonged disease-free interval and improved survival in patients with stages IIIC–IV epithelial ovarian and fallopian tube cancer. Moreover all patients with no residual tumor seem to have the best prognosis and in view of these results we believe that the goal of primary surgery should be considered as leaving no macroscopic disease.

Background and objective Patients undergoing off-pump coronary artery bypass grafting (CABG) may need emergent institution of cardiopulmonary bypass (CPB) for circulatory collapse during the operation. Our aim was to evaluate outcome in such patients and identify preoperative and intraoperative risk factors. Methods This is an observational study in a University Hospital setting. In the period June 2001-July 2003, data from 988 consecutive patients undergoing CABG in our institution were prospectively collected. No interventions were made. Prolonged hospital stay (>7 days), hospital mortality, temporal trends and risk factors for conversion from off-pump to on-pump surgery were studied. Results Fifty-four patients with emergency operations and six with associated carotid artery surgery were excluded. Of the remaining 928 patients, 450 (48.5%) were planned for off-pump surgery. Thirty-seven (8.2%) of them required conversion to CPB on an emergency basis. These patients had higher mortality (5.4%) than the off-pump group (1.5%) and the CPB group (0.4%), P = 0.02. The incidence of prolonged hospital stay was also higher (conversion group = 27%, off-pump group = 12.3%, CPB group = 17.6%; P = 0.02). We did not identify any perioperative characteristics significantly associated with the risk of requiring conversion. The conversion rate was uniformly distributed over the study period. Conclusions Patients who are emergently converted to CPB during attempted off-pump procedures are at higher risk of death and prolonged hospital stay; this population should be included in comparative studies as "intention to treat" in the off-pump group.

Background: There is evidence that cancer is immunogenic under certain situations. IL-2 is described to stimulate an effective antitumor immune response in vitro and in vivo. The ability of cancer patients to undergo surgical resection is still the most important prognostic factor for many solid tumors, including gastric adenocarcinoma. The host immune system may be further compromised by surgical procedures leading to a generalized state of immunodepression in the post-operative period. The aim of this randomized case-control study is to evaluate the effects of pre-operative low-dose IL-2 treatment on patients with gastric adenocarcinoma who undergo surgery. Methods: Sixty-eight patients with gastric adenocarcinoma were enrolled in the study and randomized in two groups: 36 patients were pre-treated with IL-2 and 32 underwent surgery without any treatment. Total peripheral WBC, neutrophils, CD3+ T, CD4+ T, CD8+ T and NK cells were obtained before and after surgery, at different times. Peritumoral infiltration was analyzed on all surgical specimens. Overall survival and relapse-free survival were studied with a median follow-up of 51 months. Results: Low-dose IL-2 treatment resulted in an increase peritumoral lymphocytic and eosinophilic infiltrations and in a minor decrease in CD3+ T and CD4+ T cells after surgery (P < 0.05). A stepwise multivariate analysis revealed that overall survival and relapse-free survival were affected only by stage of tumor and age of patients. Conclusions: According to our data low-doses of IL-2 administered pre-operatively to patients with gastric cancer activate peripheral and peri-tumoral lymphocytes but did not affect prognosis. © 2007 Society of Surgical Oncology.

Objective : Atrial fibrillation is the most common complication after coronary artery bypass graft surgery. This arrhythmia may lead to hemodynamic compromise, prolonged hospitalization, and increased risk for cerebral thromboembolism. Older age is the only variable consistently associated with the development of postoperative atrial fibrillation; however, no strong predictive model exists. The purpose of this study was to identify perioperative characteristics associated with new-onset atrial fibrillation in patients undergoing off-pump coronary artery bypass grafting. Design : Prospective, observational. Setting : University tertiary care hospital. Participants : One hundred sixty consecutive patients undergoing off-pump coronary artery bypass grafting. Interventions : None. Measurements and Main Results : Incidence of postoperative atrial fibrillation was the major outcome. Atrial fibrillation occurred in 33 patients (20.6%). Multivariate analysis identified reintervention (odds ratio 26.8), revascularization of the ramus medianus (odds ratio 3.9), and age (odds ratio 1.069 per year) as the only independent predictors of postoperative atrial fibrillation. All patients were in sinus rhythm at hospital discharge. One hospital death was noted. Conclusions : Despite the less invasive approach, the incidence of postoperative atrial fibrillation is high after off-pump coronary artery bypass grafting. Older age, grafting of the ramus medianus, and a redo operation were predictors of new-onset postoperative atrial fibrillation. It is possible that left atrial stretching with heart dislocation during revascularization of the lateral wall could lead to postoperative atrial fibrillation.

Objective: Atrial fibrillation is a common complication after cardiac surgery. Magnesium is an effective and safe antiarrhythmic agent for arrhythmias that develop after cardiac surgery. The authors performed a study to evaluate the role of perioperative magnesium for prophylaxis of atrial fibrillation after off-pump coronary artery surgery. Design: Randomized controlled study. Setting: University teaching hospital. Participants: One hundred sixty consecutive patients undergoing elective, isolated, off-pump coronary artery bypass grafting were prospectively randomized into 2 groups. Interventions: Patients in the magnesium group (n=80) received a 2.5-g (20 mEq) magnesium sulphate infusion intraoperatively over 30 minutes, and the placebo group (n=80) received normal saline solution. Measurements and main results: Postoperative atrial fibrillation occurred in 16 of 80 patients (20%) in the magnesium group and in 18 of 80 (22.5%) in the placebo group (p=0.9). Conclusion: The use of 2.5 g of intraoperative magnesium showed no effect in preventing atrial fibrillation after off-pump coronary artery bypass. (C) 2005 Elsevier Inc. All rights reserved. OBJECTIVE: Atrial fibrillation is a common complication after cardiac surgery. Magnesium is an effective and safe antiarrhythmic agent for arrhythmias that develop after cardiac surgery. The authors performed a study to evaluate the role of perioperative magnesium for prophylaxis of atrial fibrillation after off-pump coronary artery surgery.DESIGN: Randomized controlled study.SETTING: University teaching hospital.PARTICIPANTS: One hundred sixty consecutive patients undergoing elective, isolated, off-pump coronary artery bypass grafting were prospectively randomized into 2 groups.INTERVENTIONS: Patients in the magnesium group (n = 80) received a 2.5-g (20 mEq) magnesium sulphate infusion intraoperatively over 30 minutes, and the placebo group (n = 80) received normal saline solution.MEASUREMENTS AND MAIN RESULTS: Postoperative atrial fibrillation occurred in 16 of 80 patients (20%) in the magnesium group and in 18 of 80 (22.5%) in the placebo group (p = 0.9).CONCLUSION: The use of 2.5 g of intraoperative magnesium showed no effect in preventing atrial fibrillation after off-pump coronary artery bypass.

Objective: The purpose of this study was to determine whether coronary artery bypass grafting (CABG) surgery on the beating heart (BH) is associated with reduction of R-wave potentials on the precordial leads on the surface electrocardiogram (ECG) as previously shown for CABG with cardiopulmonary bypass. Methods: Fifty-four patients undergoing CABG surgery at a single tertiary care university hospital were analyzed. Patients suffering a postoperative cardiac event (myocardial infarction) or nonspecific ECG changes were excluded. ECG results were recorded at arrival in the intensive care unit, after 4 and 18 hours postoperatively; simultaneously, myocardial cell damage biomarkers (CK-MB and cTnl) were assayed. A control group of 31 patients undergoing mitral valve repair was also evaluated. Results: Patients operated with the BH (OPCABG) technique did not show any decrease of R-wave amplitude at 0, 4, and 18 hours postoperatively; whereas those operated with CPB, both for coronary artery surgery and for mitral repair, had a similar extent and pattern of R-wave reduction. The release of myocardial necrosis markers was significantly lower in coronary artery patients operated with BH than in those operated with CPB; however, no statistically significant correlation between the ECG changes and release of myocardial cell damage markers was observed in any of the groups. Conclusions: The findings indicate, for the first time, that CABG surgery on the BH is not followed by any reduction of R-wave amplitude on precordial leads and confirms that the BH technique is associated with a lower release of myocardial cell damage markers. (C) 2004 Elsevier Inc. All rights reserved.

SummaryThe urokinase-type plasminogen activator receptor (uPAR) is involved in cell migration and tissue remodelling, as a receptor for pro-uPA, as a cell adhesion component, and in a soluble form as a chemoattractant. We have analyzed the presence and the molecular forms of uPAR and uPAR-fragments in urine of ovarian cancer patients in comparison with tumour tissue, ascites, and serum. Carcinoma tissue contained high levels of uPAR, but more abundantly the D2D3-fragment. Ascitic fluid contained similar ratio’s of suPAR fragments as corresponding tumour tissue, but serum only contained intact suPAR. Interestingly, urine contained predominantly the uPAR-fragments D1 and D2D3, and the pattern of these fragments was different in cancer patients as compared to healthy individuals. To confirm the hypothesis that circulating and urinary suPAR and suPAR-fragments originate from the tumour tissue, the presence of human suPAR (fragments) was analyzed in mice xenografted with human tumours. Indeed, high levels of urinary D1 fragment were found in mice carrying a tumour displaying cleaved uPAR on the cell surface, but little or no D1 was found in the urine from mice carrying a tumour with full-length uPAR. Mouse serum contained only intact suPAR. Our data demonstrate that the enhanced levels of suPAR fragments in the urine of cancer patients is likely to originate from uPAR expressed in the tumour tissue. Considering the biological activities that uPAR fragments display, the level and typing of uPAR fragments in urine might therefore be clinically more relevant than the plain serum uPAR content.

Objective: The appearance of new Q waves on the electrocardiogram (ECG) after cardiac surgery has been traditionally considered a sign of major myocardial tissue damage. The aim of this study was to investigate the clinical significance of new Q waves appearing following cardiac surgery and to correlate them with the release of myocardial cell damage biomarkers. Methods: 206 consecutive patients undergoing cardiac surgery were prospectively evaluated. A 12 lead ECG was recorded and cardiac troponin I and creatinekinase subtraction MB assayed the day before surgery, on arrival at the intensive care Unit. 4 and 18 h postoperatively and every morning until the fifth postoperative day. Results: The incidence of new Q waves was 7.3%. Patients with isolated ECG findings had an uneventful postoperative course; on the contrary, when ECG changes were coupled with the release of myocardial necrosis biomarkers, patients had a complicated postoperative course. Conclusions: The association of a new Q wave and high levels of myocardial necrosis biomarkers is strongly associated with postoperative cardiac events. On the contrary, the isolated appearance of a new Q wave has no impact on the postoperative cardiac outcome. (C) 2004 Elsevier B.V. All rights reserved.