Mauro Melpignano

A multicentre collaborative study on the use of cold scalpel and electrocautery for midline abdominal incision.

BACKGROUND Although studies in animals demonstrated a better wound healing after abdominal incision with cold scalpel than with electrocautery, clinical experiences did not confirm these findings. The purpose of this study was to compare early and late wound complications between diathermy and scalpel in gynecologic oncologic patients undergoing midline abdominal incision. METHODS Patients undergoing midline abdominal incision for uterine malignancies were divided into two groups according to the method used to perform the abdominal midline incision: cold scalpel and diathermy in coagulation mode. Early and late complications were compared. Logistic regressions were used for statistical analysis. RESULTS Nine hundred sixty-four patients were included, of whom 531 were in the scalpel group and 433 in the electrocautery group. Both groups were similar with respect to demographic, operative, and postoperative characteristics. Univariate analysis revealed a higher incidence of severe wound complications in the scalpel group than in the electrocautery group (8 of 531 versus 1 of 433, P <0.05). After adjustment for confounding variables (eg, age, body mass index) no differences were found between groups. CONCLUSIONS Scalpel and diathermy are similar in terms of early and late wound complications when used to perform midline abdominal incisions. Therefore the choice of which method to use remains only a matter of surgeon preference.

Survival of women with advanced ovarian cancer and complete pathologic response at second-look laparotomy

The purpose of the study was to analyze the determinants of long term survival in women with advanced ovarian cancer and negative second‐look laparotomy.

Paclitaxel 175 or 225 mg per Meters Squared With Carboplatin in Advanced Ovarian Cancer: A Randomized Trial

PURPOSE To analyze the effect of different doses of paclitaxel with fixed doses of carboplatin in the treatment of ovarian cancer. PATIENTS AND METHODS Patients with histologically confirmed epithelial ovarian cancer, International Federation of Gynecology and Obstetrics stages IIB to IV, were eligible for this randomized, multicenter study. Women were randomly assigned to treatment with (1) carboplatin at the dose (in milligrams) corresponding to the following formula: target area under the free carboplatin plasma concentration versus time curve (AUC) = 6 x (glomerular filtration rate + 25) mg/m(2) (AUC6) plus paclitaxel 175 mg/m(2) for six cycles every 21 days or (2) carboplatin AUC6 plus paclitaxel 225 mg/m(2) for six cycles every 21 days. A total of 502 women entered the study. RESULTS Pathologic complete response was documented in 132 patients (63.8%) in the 175 mg/m(2) group and in 127 cases (55.7%) in the 225 mg/m(2) group (chi(2) P =.090). The 4-year progression-free survival rate was 41.5% (SE = 3.5) in the 175-mg group and 39.2% (SE = 3.5) in the 225-mg group. The corresponding 4-year survival rates were 46.2% (based on 115 deaths) and 47.3% (based on 113 deaths), respectively. CONCLUSION This randomized trial suggests that paclitaxel 175 mg/m(2) plus carboplatin AUC6 is the schedule with a more favorable profile than paclitaxel 225 mg/m(2) plus carboplatin AUC6.

Preoperative Transvaginal Ultrasonography and Intraoperative Gross Examination for Assessing Myometrial Invasion by Endometrial Cancer

Endometrial cancer is the most common gynecologic malignancy. The cornerstone of treatment remains surgery according to International Federation of Gynecology and Obstetrics staging. The aim of this study was to evaluate the concordance between myometrial infiltration detected by ultrasonography and gross examination with respect to definitive histologic examination and to select a population in which lymphadenectomy could be excluded. We also evaluated the concordance for the degree of tumor differentiation between diagnostic biopsy and final histologic results.

Secondary analyses from a randomized clinical trial: age as the key prognostic factor in endometrial carcinoma

OBJECTIVE The purpose of this study was to explore in greater depth the outcomes of the Italian randomized trial investigating the role of pelvic lymphadenectomy in clinical early stage endometrial cancer. In the attempt to identify the patients with poorer prognosis, the impact of age and body mass index were also thoroughly investigated by cancer-specific survival (CSS) analyses. STUDY DESIGN Survival outcomes of trial patients were analyzed in relation to age (≤65 years and >65 years) in the 2 arms (lymphadenectomy and no lymphadenectomy) and in the whole population of the trial. RESULTS Univariate and multivariable analyses of CSS and overall survival (OS) of patients showed that age >65 years is a strong independent poor prognostic factor (5-y OS 92.1% and 78.4% in ≤65 years and >65 years patients, respectively, P < .0001; 5-y CSS 93.8% and 83.5% in ≤65 years and >65 years patients, respectively, P = .003). Among women ≤65 years, node negative patients had 94.4% 5-y OS and 96.3% 5-y CSS vs 74.3% 5-y OS and 74.3% 5-y CSS for node positive patients (P = .009 and P = .002, respectively), while among women >65 y, node negative patients had 75.7% 5-y OS and 83.6% 5-y CSS vs 74.1% 5-y OS and 83.3% 5-y CSS for node positive patients (P = .55 and P = .58, respectively). Univariate and multivariable survival analyses in the whole trial population showed that older age, and higher tumor grade and stage were significantly associated to a worse prognosis. CONCLUSION Older women faced an intrinsic poorer survival whether or not they underwent lymphadenectomy, and, unexpectedly, irrespective of the presence of nodal metastasis. Only in older patients was obesity (body mass index >30) significantly associated with scarce prognosis.

A phase 2 multicenter study of irinotecan and cisplatinum as neoadjuvant treatment in patients with locally advanced cervical cancer.

Hypothesis: To evaluate efficacy and safety of a neoadjuvant treatment with irinotecan and cisplatin [cis-diamminedichloroplatinum(II); CDDP] in patients with locally advanced cervical cancer. Methods: A phase 2 study was conducted at 13 centers located in Italy. Eighty-seven were enrolled between 2000 and 2003. Patients received irinotecan 175 mg/m2 on day 1 every 3 weeks followed by CDDP 80 mg/m2. Each patient was to receive 3 cycles of treatment. Tumor response was to be evaluated by magnetic resonance imaging 3 weeks after the end of the third cycle. At the end of therapy, all patients were to be examined for radical surgery. Results: Of 71 patients included in the primary analysis, 9 (12.7%) showed a complete response; and 43 (60.6%), a partial response for an overall response rate of 73.2% (95% confidence interval [CI], 61.4%-83.1%). Complete pathological responses were observed in 13.6% of the patients (95% CI, 7.0%-23.0%). Overall survival rate at 4 years was 87.0% (95% CI, 79.5%-94.5%). There were no study-related deaths. Most common adverse events were alopecia in 76 patients (87.4%) and gastrointestinal disorders in 79 patients (90.8%). Serious adverse events were vomiting in 18 patients (20.7%), nausea in 14 (16.1%), diarrhea in 8 (9.2%), and neutropenia in 50 (57.5%). A total of 3 patients (3.4%) were discontinued from the study owing to the occurrence of 1 or more serious adverse event. Conclusions: Irinotecan and CDDP as neoadjuvant chemotherapy in locally advanced cervical cancer showed a promising response rate. These data warrant confirmation with a phase 3 study.

Role of human papillomavirus in the development of epithelial ovarian neoplasms in Italian women

Aim:  In this article, for the first time, we investigate the presence of human papillomavirus (HPV) DNA in ovarian epithelial neoplasms from a group of 71 Italian women. The follow ups of the patients with or without HPV DNA were also considered to evaluate whether HPV DNA in these tumors could be an indicator of prognosis.

Randomised prospective study of abdominal wall closure in patients with gynaecological cancer.

Background:  Median laparotomy is the most common approach to the abdominopelvic cavity in patients with gynaecological tumours.

Human papilloma virus (HPV) status, p16INK4a, and p53 overexpression in epithelial malignant and borderline ovarian neoplasms.

This investigation is the first to evaluate simultaneously human papilloma virus (HPV) status, p16(INK4a), and p53 immunoreactivity in epithelial ovarian neoplasms. The results were analyzed and correlated with histological type, histological grade, and survival of patients. Subtypes considered are papillary serous and mucinous. Polymerase chain reaction (PCR) analysis, performed in our previous study, had already demonstrated a small number of HPV-positive epithelial ovarian neoplasms. No significant correlation was found between the presence of HPV DNA and subtypes of ovarian neoplasms; thus, HPV cannot be considered responsible for epithelial ovarian neoplasm. Since p16 immunoreactivity was present in many other HPV-negative cases of epithelial ovarian neoplasms, this study suggests that p16 overexpression in some neoplasms of the female genital tract is not related to HPV carcinogenesis. A higher p53 expression rate observed between borderline and malignant serous tumors and between serous and mucinous neoplasms can confirm a recent dualistic model of ovarian carcinogenesis. According to this theory, low-grade serous carcinomas (serous intraepithelial carcinomas, serous borderline neoplasm, and ovarian mucinous neoplasms) (type I tumors) develop from mutations of KAS and BRAF, while high-grade serous carcinomas (type II tumors) develop from mutation of p53. In malignant neoplasms, for univariate analysis, patient survival seems to be related to p53, strong and diffuse p16 overexpression, and the stage of development of neoplasms at the diagnosis. In multinomial logistic regression, used to evaluate the role of staging, grading, p16 and p53 immunopositivity as predictor variables of unfavorable outcome of the disease, only p16 positivity was significantly related to the poor prognosis of the cancer.

A phase I–II trial of fixed-dose carboplatin and escalating paclitaxel in advanced ovarian cancer

We conducted a phase I-II study with escalating paclitaxel doses plus carboplatin at a fixed dose for previously untreated patients with advanced ovarian cancer in order to define the maximum tolerated dose. Eligible for the study were women with a histologically confirmed diagnosis of ovarian cancer stage III-IV according to the FIGO classification. In the first phase of the study, 6 patients were allocated escalating paclitaxel doses with fixed-dose carboplatin in order to establish the maximum tolerated dose. The starting dose of paclitaxel was 150 mg/m2 given after carboplatin (300 mg/m2) every 4 weeks for a total of six courses. The paclitaxel dose step was 25 mg/m2 up to 250 mg/m2. The study then progressed to a phase II trial using the maximum tolerated paclitaxel dosage reached during the escalating dose phase. A total of 27 patients entered phase I and 23 phase II. Neurotoxicity was observed in 47 patients (94%; 29 grade 1, 17 grade 2, 1 grade 3, according to the WHO classification). The intensity of neurotoxicity tended to be dose related: out of the 15 patients who received < or = 200 mg paclitaxel, a total of 14 grade 1, but no grade 2 or 3 neurotoxicities, were observed. The frequency of grade 1, 2 and 3 neurotoxicity was 15, 17 and 1, respectively, in the 35 women who received > or = 225 paclitaxel +300 mg carboplatin. There was no clear relationship between median WBC and platelet nadir and dose level. Among other toxicities, alopecia was observed in all 50 cases, hypersensitivity in two (4%) and myalgia in 41 (82%; 34 grade 1 and 7 grade 2). These frequencies tended to increase with the dose, but the relationship was not statistically significant. The overall response rate was 78% (39/50) with a complete response rate of 62% (31/50). In conclusion, this study suggests that carboplatin and paclitaxel can be administered safely to patients with advanced ovarian carcinoma. The maximum dose reached was 250 mg/m2 paclitaxel and 300 mg/m2 for carboplatin, but from a clinical point of view the maximum paclitaxel dose we would consider safe is 225 mg/m2.