Giuseppe Vizzielli

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.

Role of CT scan-based and clinical evaluation in the preoperative prediction of optimal cytoreduction in advanced ovarian cancer: a prospective trial

Background:In advanced ovarian cancer, maximal efforts have to be attemptedto achieve optimal cytoreduction, as this represents the keystone in the therapeutic management. This large, prospective study aims at investigating the role of computed tomography (CT) scan in predicting the feasibility of optimal cytoreduction in ovarian cancer.Methods:A total of 195 consecutive patients with clinical/radiographic suspicion of advanced ovarian/peritoneal cancer were enrolled at the Gynecologic Oncology Unit, Catholic University of Rome and Campobasso, Italy. Preoperative CT scans were performed with a high-speed scanner (CT Hi Speed Nx/i Pro; 2-slice; GE Medical System). All patients underwent standard laparotomy, and maximal surgical effort was attempted. The following CT parameters were used: peritoneal thickening, peritoneal implants >2 cm, bowel mesentery involvement, omental cake, pelvic sidewall involvement and/or hydroureter, suprarenal aortic lymph nodes >1 cm, infrarenal aortic lymph nodes >2 cm, superficial liver metastases >2 cm and/or intraparenchimal liver metastases any size, large volume ascites (>500 ml). Clinical data included were age, Ca125 serum levels, and ECOG-PS. Radiographic and clinical features exhibiting a specificity >75%, a positive and negative predictive value >50%, an accuracy >60% in predicting surgical outcome were assigned a point value of 2. With this scoring system, a predictive index (PI) was calculated for each patient.Results:The PI scores ranged from 0 to 6, and from 0 to 8, in Model 1 (including only radiographic parameters) and in Model 2 (including radiographic and clinical data). The AUC was 0.78+0.035 in Model 1, and 0.81+0.031 in Model 2. Therefore, the addition of ECOG-PS data led to the improvement of the diagnostic performances (z=2.41, P-value <0.05).Conclusions:Computed scan still represents a valid tool to predict ovarian cancer optimal cytoreduction; the predictive ability of a CT scan-based model is improved by integrating ECOG-PS data.

Cytoreductive surgery plus HIPEC in platinum-sensitive recurrent ovarian cancer patients: A case-control study on survival in patients with two year follow-up

OBJECTIVES To compare survival data in platinum-sensitive recurrent ovarian cancer patients submitted to secondary cytoreduction (SCR) plus hyperthermic intraperitoneal intraoperative chemotherapy (HIPEC) (Cases) and a similar group of women not experiencing HIPEC (Controls). METHODS Case-control study, matching 30 Cases with 37 Controls, with at least 24 months of follow-up. RESULTS Groups were comparable for all characteristics, except for a higher proportion of patients with single-nodule relapses is the Controls (19 vs. 6; p=0.011). Median follow-up time was 46 months in the Cases and 36 months in the Controls. Twenty patients (66.6%) experienced secondary recurrence in the Cases and 37 women (100%) in the Controls (p=0.001). Moreover, 7 (23.3%) and 23 (62.2%) patients died of disease in the Cases and Controls respectively (p=0.003). The duration of secondary response was 26 months in the Cases and 15 months in the Controls (p=0.004). CONCLUSIONS The combination of SCR and HIPEC seems to improve survival rate in patients suffering from platinum-sensitive EOC recurrence with respect to no-HIPEC treatments. This result further supports the need of a randomized trial.

Secondary cytoreduction plus oxaliplatin-based HIPEC in platinum-sensitive recurrent ovarian cancer patients: A pilot study

OBJECTIVES To assess feasibility, complications and efficacy of secondary surgical cytoreduction (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in a selected group of platinum-sensitive recurrent ovarian cancer patients. METHODS Recurrent ovarian cancer patients with a platinum-free interval of at least 6 months were prospectively enrolled. After complete CRS they were submitted to intraperitoneal perfusion of oxaplatinum (460 mg/m(2)) heated to 41.5 degrees C for 30 min. Then they received systemic chemotherapy with taxotere 75 mg/m(2) and oxaliplatin 100 mg/m(2) for 6 cycles. Patients were followed up routinely until recurrence or death. RESULTS Twenty-five recurrent ovarian cancer patients were valuable for the study. The median Platinum Free Interval (PFI) was 25 months (range 7-67). The majority of the patients (76%) had diffuse carcinosis. Nobody had ascites. An optimal residual disease was obtained in all patients. The median duration of CRS+HIPEC was 312 min (range 138-619). Median intensive care unit (ICU) stay was 2 days (1-6), median hospital stay was 13 days (7-30). Post-operative major complications were observed in 7 patients (28%). Post-operative mortality was 0%. With a median follow-up time of 18 months (range 3-38), 24 patients (96%) are alive, but seven women (28%) have relapsed. CONCLUSIONS Adequate pre-operative selection can improve feasibility of CRS and HIPEC. Morbidity rate is comparable to aggressive cytoreduction without HIPEC. Although associated with some post-operative morbidity, long-term results are encouraging, waiting for larger series and longer follow-up data.

A multicentric trial (Olympia–MITO 13) on the accuracy of laparoscopy to assess peritoneal spread in ovarian cancer

OBJECTIVE The objective of the study was to prospectively evaluate the accuracy of laparoscopy performed in satellite centers (SCs) to describe intraabdominal diffusion of advanced ovarian cancer (AOC). STUDY DESIGN Patients with a clinical/radiological suspicion of AOC were included in the protocol. SCs were selected among those surgeons, spending a short intensive training period at the coordinator center (CC) to learn the application of staging laparoscopy (S-LPS) in AOC. All women underwent S-LPS at the SCs, and the surgical procedure was recorded and blindly reviewed at the CC. Calculating specificity, positive and negative predictive values, and the accuracy for each parameter with respect to the CC assessed the diagnostic performance of S-LPS. The Cohens kappa was used to test the interobserver agreement of each parameter. RESULTS One hundred sixty-eight cases were considered eligible for the study. A per-protocol analysis was performed on 120 cases. The worst laparoscopic assessable feature was mesenteric retraction, whereas the remaining variables ranged from 99.2% (peritoneal carcinomatosis) to 90% (bowel infiltration). All but 1 SC (SC number 4) reached an accuracy rate of 80% or greater for both single parameters and overall score. The Cohens kappa and the P value for overall predicitive index value were 0.685 and .01, respectively, but improved to 0.773 and .388 after removing the SC number 4 from the analysis. CONCLUSION S-LPS allows an accurate and reliable assessment of intraperitoneal diffusion of disease in AOC patients in trained gynecological oncology centers.

HIPEC in recurrent ovarian cancer patients: Morbidity-related treatment and long-term analysis of clinical outcome

OBJECTIVE To evaluate morbidity and mortality rates associated with the use of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) after optimal cytoreduction (CRS) in a large single-institutional series of platinum-sensitive recurrent ovarian cancer patients. Moreover, disease free (DFS) and overall survival (OS) of previously studied patients have been assessed after a longer follow-up period. METHOD From May 2005 to October 2010, recurrent ovarian cancer patients with a platinum-free interval of at least 6 months have been prospectively enrolled in a protocol of CRS plus HIPEC with oxaplatinum (460 mg/m(2)) heated to 41.5 °C for 30 min, followed by 6 cycles of systemic chemotherapy with taxotere 75 mg/m(2) and oxaliplatin 100 mg/m(2). RESULTS Forty-one patients experienced 43 procedures (CRS+HIPEC). An optimal cytoreduction was achieved in all cases (CC-0 95.3%; CC-1 4.7%). A complication rate of 34.8% was registered, with no case of intraoperative death or within 30 days after surgery. Survival curves have been calculated in a group of 25 patients with a minimum follow-up of 18 months, obtaining a median DFS and OS of 24 (range 6-60) and 38 months (range 18-60), respectively. CONCLUSION In recurrent platinum-sensitive ovarian cancer patients, the use of CRS plus HIPEC represents a safe treatment, able to significantly influence the survival rates compared to chemotherapy alone or surgery plus standard chemotherapy.

Cytoplasmic expression of estrogen receptor beta (ERβ) predicts poor clinical outcome in advanced serous ovarian cancer.

OBJECTIVE In this study we investigated the prognostic value of estrogen receptor α (ERα), ERβ and progesterone receptor (PR) expression in 58 untreated advanced serous ovarian cancer patients. The study also included 12 macroscopically and histopathologically normal ovaries. MATERIALS AND METHODS Protein expression was evaluated by immunohistochemistry, and antibody staining detected in both the nuclear and cytoplasmic compartments was taken into account. Immunopositivity was analyzed in relation to tumor clinicopathological variables, disease-free survival (DFS), and overall survival (OS). RESULTS Epithelial cells in ovarian cancer tissue showed significantly lower levels of nuclear ERβ and PR, but not ERα, than in normal ovarian tissue. In the case of ERβ, however, while normal ovarian epithelium exhibited almost exclusively strong nuclear staining, ovarian cancer tissue mostly showed cytoplasmic immunopositivity. Nuclear ERα and ERβ expression were not associated with clinical outcome. Conversely, any cytoplasmic ERβ expression was an independent unfavorable prognostic factor for DFS, a finding approaching statistical significance also for OS. These data suggest that, in advanced serous ovarian cancer, cytoplasmic ERβ signaling may be more important for patient survival than its nuclear signaling. In the case of PR, positivity was an independent favorable prognostic factor for DFS. CONCLUSIONS These novel findings, that need to be confirmed in a large prospective trial, suggest that additional prognostic, and possibly therapeutic opportunities may be available in advanced serous ovarian cancer.

Upper abdominal surgery in advanced and recurrent ovarian cancer: Role of diaphragmatic surgery

OBJECTIVE Upper abdominal spread of primary and recurrent ovarian cancer is often considered to be a major obstacle to achieve optimal residual disease at the end of surgery. In this study, we investigate the role of diaphragmatic debulking in the natural history of advanced and recurrent epithelial ovarian cancer patients, and the morbidity of this procedure according to clinico-surgical characteristics. METHODS Data from 234 consecutive patients with primary and recurrent advanced ovarian cancer, operated at Catholic University of Rome and Campobasso from January 1, 2005 and December 31, 2008, were retrospectively reviewed. RESULTS Eighty-seven patients (37.2%) underwent a diaphragmatic surgery. Median age was 55 years (range 37-76). Diaphragmatic debulking was performed in 50 out of 120 patients at primary surgery (41.7%), in 16 out of 74 at interval debulking surgery (21.6%) and in 21 out of 40 secondary cytoreductions (52.5%). In the whole study population optimal residual disease at the end of surgery was achieved. The most frequent post-operative complication was pleural effusion, observed in 37 patients (42.5%). Presence of a post-operative pleural effusion was correlated liver mobilization (52.3% vs. 16%; p<0.0027) and large diaphragmatic disease (>5 cm) removal (54.1% vs. 23.5%; p<0.034). CONCLUSIONS Diaphragmatic surgery represents a crucial step in the debulking of advanced and recurrent ovarian cancer patients. Considering the natural history of advanced epithelial ovarian cancer and the rate of patients needing diaphragmatic debulking during primary cytoreduction, interval debulking surgery and secondary cytoreduction, this procedure should be present in the surgical repertoire of a gynecologic oncologist.

Definition of a dynamic laparoscopic model for the prediction of incomplete cytoreduction in advanced epithelial ovarian cancer: Proof of a concept

OBJECTIVE To develop an updated laparoscopy-based model to predict incomplete cytoreduction (RT>0) in advanced epithelial ovarian cancer (AEOC), after the introduction of upper abdominal surgery (UAS). PATIENTS AND METHODS The presence of omental cake, peritoneal extensive carcinomatosis, diaphragmatic confluent carcinomatosis, bowel infiltration, stomach and/or spleen and/or lesser omentum infiltration, and superficial liver metastases was evaluated by staging laparoscopy (S-LPS) in a consecutive series of 234 women with newly diagnosed AEOC, receiving laparotomic PDS after S-LPS. Parameters showing a specificity≥75%, PPV≥50%, and NPV≥50% received 1 point score, with an additional one point in the presence of an accuracy of ≥60% in predicting incomplete cytoreduction. The overall discriminating performance of the LPS-PI was finally estimated by ROC curve analysis. RESULTS No-gross residual disease at PDS was achieved in 135 cases (57.5%). Among them, UAS was required in 72 cases (53.3%) for a total of 112 procedures, and around 25% of these patients received bowel resection, excluding recto-sigmoid resection. We observed a very high overall agreement between S-LPS and laparotomic findings, which ranged from 74.7% for omental cake to 94.8% for stomach infiltration. At a LPS-PIV≥10 the chance of achieving complete PDS was 0, and the risk of unnecessary laparotomy was 33.2%. Discriminating performance of LPS-PI was very high (AUC=0.885). CONCLUSIONS S-LPS is confirmed as an accurate tool in the prediction of complete PDS in women with AEOC. The updated LPS-PI showed improved discriminating performance, with a lower rate of inappropriate laparotomic explorations at the established cut-off value of 10.