Carlo De Cicco Nardone

Neoadjuvant chemotherapy plus radical surgery followed by chemotherapy in locally advanced cervical cancer

OBJECTIVES To evaluate the efficacy, in terms of safety, overall survival and progression free survival of neoadjuvant chemotherapy followed by radical surgery plus adjuvant chemotherapy in patients affected by locally advanced cervical cancer (stage IB2-IIB) with or without node metastases. METHODS Between June 2000 and February 2007, all patients with diagnosis of locally advanced cervical cancer referred to the Division of Gynecologic Oncology of the University Campus Bio-Medico of Rome were eligible for this protocol. All enrolled patients received 3 cycles of platinum-based chemotherapy every 3 weeks according to the scheme Cisplatin 100mg/mq and Paclitaxel 175 mg/mq. After neoadjuvant chemotherapy all patients with stable or progressive disease were excluded from the protocol, the others were submitted to classical radical hysterectomy, bilateral salpingo-oophorectomy and bilateral systematic pelvic lymphadenectomy and 4 cycles of adjuvant treatment with platinum based chemotherapy were executed. RESULTS Concerning intention to treat basis analysis, 5 year overall survival (OS) and disease-free survival (DFS) are 77% and 61%, respectively. The 5-year OS of patients with positive pelvic nodes and those with negative nodes metastases was respectively 60% and 87%. Concerning the according to protocol analysis, the 5-year OS and DFS are 81% and 70% respectively. The 5-year OS in patient with positive and negative lymph nodes is 75% and 88% respectively. CONCLUSIONS The adjuvant chemotherapy regimen after neoadjuvant chemotherapy and radical surgery represents a valid treatment for patients with locally advanced cervical cancer.

A comparison of three different entry techniques in gynecological laparoscopic surgery: a randomized prospective trial

OBJECTIVE Laparoscopic entry techniques vary and still remain debated. We conducted a randomized control trial to compare three entry techniques. STUDY DESIGN Women aged 18-70 years, nominated for laparoscopic surgery at University of Rome Campus Bio-Medico, were randomized into three different groups: Veress needle (VER), Direct trocar insertion (DIR) and Open technique (OP). For each group, minor complications (extra-peritoneal insufflation, trocar site bleeding, omental injury and surgical site infection), failed entry and time of entry of the main trocar were evaluated. Major complications were also considered. Between-group comparisons were performed using chi-square test. Significance P value was <0.05. RESULTS A series of 595 consecutive procedures were included: 193 in the VER group, 187 in the DIR group and 215 in the OP group. Minor complications occurred in 36 cases: extraperitoneal insufflation (n=6) in the VER group only, site bleeding (n=2 in the VER group, n=2 in the DIR group and n=1 in the OP group), site infection (n=5 in the VER and n=6 in OP group), and omental injury (n=6 in the VER group and n=3 in the DIR group). Failed entry occurred in 4 cases of the VER group and 1 case of the DIR group. Mean time of entry was 212.4, 71.4 and 161.7s for the VER, DIR and OP groups respectively. Among major complications, one bowel injury resulted following the Veress technique. CONCLUSIONS In our series, DIR and OP entry presented a lower risk of minor complications compared with VER. In addition, time of entry was shorter in DIR than with OP entry.

REM (RISK OF ENDOMETRIAL MALIGNANCY): A PROPOSAL FOR A NEW SCORING SYSTEM TO EVALUATE RISK OF ENDOMETRIAL MALIGNANCY .

Purpose: It is often difficult to distinguish a benign endometrial disease from a malignancy and tools to help the physician are needed to triage patients into high and low risk of endometrial cancer. The purpose of this study was to obtain a predictive model to assess the risk of endometrial malignancy (REM) in women with ultrasound endometrial abnormalities. Experimental Design: Women, between ages 45 to 80 years, diagnosed through ultrasound with endometrial abnormalities and scheduled to have surgery were enrolled on a prospective study at the Department of Gynaecologic Oncology of Campus Bio-Medico, University of Rome. Preoperative clinical, ultrasound and laboratory characteristics were taken into account. Logistic regression algorithm was used to categorize patients into low- and high-risk groups for endometrial cancer. Results: A total of 675 patients were considered for the analysis: 88 with endometrial cancer and 587 with benign endometrial disease. We divided the patients into two groups: training set (TS) and verification set (VS). Preoperative age, symptom, HE4 levels, and ultrasound endometrial thickness were found statistically significant, and were included into a multivariate logistic regression model to determine the probability to have endometrial cancer. In the TS, REM reported 93.3% sensitivity and 97.1% specificity [positive predictive value (PPV), 0.83; negative predictive value (NPV), 0.98; AUC, 0.957; 95% confidence interval (CI), 0.908–0.984]. In the VS, REM reported 89.3% sensitivity and 95.4% specificity (PPV, 0.73; NPV, 0.98; AUC, 0.919; 95% CI, 0.829–0.970). Conclusions: Our data support the use of REM to triage patients into low- and high-risk groups for endometrial cancer, even if an external validation of the model is needed. Clin Cancer Res; 19(20); 5733–9. ©2013 AACR.

The role of novel biomarker HE4 in the diagnosis, prognosis and follow-up of ovarian cancer: a systematic review

ABSTRACT Introduction: Ovarian cancer is the leading cause of death from gynecologic cancers, in fact, >80% of cases are diagnosed as advanced-stage disease associated with a high mortality rate (<40% of women cured). A systematic review was performed to estimate the role of HE4 in the diagnosis, prognosis and follow-up of ovarian tumors. Areas covered: A comprehensive search of the literature from January 1952 to August 2016 was conducted using the terms ‘ovarian tumor’ and ‘ovarian cancer’ combined with ‘HE4’ and ‘human epididymis protein 4’. The search identified a total of 259 citations, of which 141 were potentially relevant after initial evaluation. Of these studies, 75 primary studies met the inclusion criteria and were analyzed, with a total of 14,773 patients. Expert commentary: Serum HE4 dosage is a useful preoperative test for predicting the benign or malignant nature of pelvic masses. It seems to have a promising role in the prediction of clinical and surgical outcomes. Moreover, HE4 seems to better predict recurrence in comparison to CA-125.

The Role of He4, a Novel Biomarker, in Predicting Optimal Cytoreduction After Neoadjuvant Chemotherapy in Advanced Ovarian Cancer

Objectives This study aimed to evaluate serum human epididymis protein 4 (HE4) changes during neoadjuvant chemotherapy (NACT) to establish HE4 predebulking surgery cutoff values and to demonstrate that CA125, HE4, and computed tomography (CT) taken together are better able to predict complete cytoreduction after NACT in advanced ovarian cancer patients. Methods From January 2006 to November 2015, patients affected by epithelial advanced ovarian cancer (International Federation of Gynecology and Obstetrics stage III–IV), considered not optimally resectable, were included in this prospective study. After 3 cycles of NACT, all patients underwent debulking surgery and were allocated, according to residual tumor (RT), into group A (RT = 0) and group B (RT > 0). Serum CA125, HE4, and CT images were recorded during NACT and compared singularly and with each other in term of accuracy, sensitivity, specificity, and positive and negative predictive value. Results A total of 94 and 20 patients were included in group A and group B, respectively. The HE4 values recorded before debulking surgery correlated with RT. The identified HE4 cutoff value of 226 pmol/L after NACT was able to classify patients at high or low risk of suboptimal surgery, with a sensitivity of 75% and a specificity of 85% (positive predictive value, 0.87; negative predictive value, 0.70). The combination of CA125, HE4, and CT imaging resulted in the best combination with a sensitivity of 96% and a specificity of 92% (positive predictive value, 0.96; negative predictive value, 0.94). Conclusions The novel biomarker HE4, in addition to CA125 and CT, is better able to predict the RT at debulking surgery and the prognosis of patients.

Anterior colporrhaphy plus inside‐out tension‐free vaginal tape for associated stress urinary incontinence and cystocele: 10‐year follow up results

We report the success rate and complications rate of combined ultralateral anterior Colporrhaphy plus Tension‐free Vaginal Tape (TVT‐O) in a long‐term (10 year) follow‐up prospective survey.

Implementing the Risk of Endometrial Malignancy Algorithm (REM) adding obesity as a predictive factor: Results of REM-B in a single-center survey

OBJECTIVE In 2013, our group assessed a risk stratification tool of endometrial cancer (EC), called REM (Risk of Endometrial Malignancy). A well known risk factor for EC is body mass index (BMI). In fact, (BMI > 30 and <35 kg/m2) and severe obesity (BMI > 35 kg/m2) were associated with a 2.6-fold and a 4.7-fold increase in EC risk, respectively. Therefore, in the present study we aim to improve the performance of REM, including BMI and developing a new scoring system, called REM-B (Risk of Endometrial Malignancy score associated to BMI), to classify patients into high risk or low risk groups for EC. STUDY DESIGN Women, between 45 and 80 years, diagnosed with ultrasound endometrial abnormalities and scheduled to have surgery were enrolled on a prospective study at Department of Gynaecologic Oncology of Campus Bio-Medico of Rome. Preoperative clinical, ultrasound and laboratory features were taken into account. RESULTS A total of 675 patients (88 with EC and 587 with benign endometrial disease) were divided in training set (TS) and verification set (VS). Age, symptom, BMI, HE4 levels and ultrasound endometrial thickness were found statistically significant and included into multivariate logistic regression model in order to determine the probability to have EC. REM-B showed an overall sensitivity of 94.7% (versus 92% of REM) and a specificity of 97.4% (versus 96% of REM). CONCLUSIONS Our data support the use of REM-B to triage patients into low and high risk of EC, even if an external validation of model is needed.

Reply to: Is there only CO2

We were honored to receive comments by Prof. Mynbaev [1] regarding our recent publication entitled: ‘‘Influence of pneumoperitoneum pressure on surgical field during robotic and laparoscopic surgery: a comparative study’’ [2]. The aim of our study was the evaluation of surgical field modifications related to variations in CO2 insufflation pressure, both during laparoscopic and robotic surgery. The two surgical procedures are technically very similar, both involving the use of the pneumoperitoneum to determine the distension of the abdominal cavity. Although these techniques are considered minimally invasive, intraabdominal CO2 insufflation is the cause of hemodynamic changes and metabolic effects; in particular, insufflation pressure and duration of pneumoperitoneum lead to damage of the mesothelium and adhesions formation, with clinical subsequences [3]. ‘‘The higher the pressure, the better the view’’ is a remark classically heard from laparoscopic surgeons [4]. This axiom is only true within limits; working space increment related to increase in insufflation pressure, in fact, is much more evident at lower than higher intra-abdominal pressures. This can be explained by the mechanical properties of the abdominal wall. The abdominal wall becomes progressively less compliant at higher levels of deformation (stretch) [5]. Song et al. [6, 7] described anisotropic mechanical properties of the abdominal wall on the basis of the orientation of stiff connective tissue fibers. As explained in physiology textbooks, muscle-containing tissues have active and passive states where muscle tone greatly influences mechanical properties [8]. The stretching of muscles also influences the maximum force their sarcomeres can generate [9]. This makes the abdominal wall a nonlinear, anisotropic, dynamic, and difficult-to-describe mechanical entity. With our study, we demonstrated that the values of intra-abdominal pressure used to obtain the pneumoperitoneum do not significantly affect the display of the abdomino-pelvic cavity in robotic surgery, differently from laparoscopic procedures where higher pressure are needed in order to perform adequate surgery. This finding is particularly significant especially at low CO2 pressure (5 mmHg), and it has considerable implications both in terms of intraoperative cardiocirculatory parameters and of peritoneal damage with consequent influence on the postoperative recovery. According to our study, Prof. Mynbaev suggested that there is an impact of pre-stretching of the abdominal wall in a case where initially we have evaluated a high insufflation pressure (15 mmHg) and then lower pressures (10 and 5 mmHg) which may bias our results. To support this hypothesis, they cited the study by Vlot et al. [10]. With this trial the authors examined the effect of pre-stretching on CO2 pneumoperitoneum volume in 24 pigs. In all animals, working-space dimensions were assessed at 0, 5, 10, and 15 mmHg. Working space was reassessed in a second run of insufflation up to 5 mmHg. All the measurements were made using CT images. Pre-stretching of the abdominal wall by a previous stepwise insufflation with This reply refers to the comment available at doi:10.1007/s00404-015-3876-x.