Saverio Tateo

Phase III randomised study to evaluate the role of adjuvant pelvic radiotherapy in the treatment of uterine sarcomas stages I and II: An European Organisation for Research and Treatment of Cancer Gynaecological Cancer Group Study (protocol 55874)

The management of uterine sarcomas continues to present many difficulties. Primary surgery is the optimal treatment but the role of post-operative radiation remains uncertain. In the mid-1980s, the European Organisation for Research and Treatment of Cancer Gynaecological Cancer Group Study proposed a trial to evaluate adjuvant radiotherapy, as previous non-randomised studies had suggested a survival advantage and improved local control when post-operative radiation was administered. The study opened in 1987 taking 13 years to accrue 224 patients. All uterine sarcoma subtypes were permitted. Patients were required to have undergone as a minimum, TAH and BSO and wahsings (166 patients) but nodal sampling was optional. There were 103 leiomyosarcomas (LMS), 91 carcinosarcomas (CS) and 28 endometrial stromal sarcomas (ESS). Patients were randomised to either observation or pelvic radiation, 51 Gy in 28 fractions over 5 weeks. Hundred and twelve were recruited to each arm. The initial analysis has shown a reduction in local relapse (14 versus 24, p=0.004) but no effect on either OS or PFS. No unexpected toxicity was seen in the radiation arm. No difference in either overall or disease-free survival was demonstrated but there is an increased local control for the CS patients receiving radiation but without any benefit for LMS. Prognostic factor analysis shows that stage, age and histological subtype were important predictors of behaviour which may explain differences between CS and LMS. CS appears to show more kinship to poorly differentiated endometrial carcinomas in behaviour. LMS did not show the same benefit from radiation. These results will help shape future management and clinical trials in uterine sarcomas.

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.

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.

Asymptomatic bacteriuria treatment is associated with a higher prevalence of antibiotic resistant strains in women with urinary tract infections.

BACKGROUND Women suffering from recurrent urinary tract infections (rUTIs) are routinely treated for asymptomatic bacteriuria (AB), but the consequences of this procedure on antibiotic resistance are not fully known. The aim of this study was to evaluate the impact of AB treatment on antibiotic resistance among women with rUTIs. METHODS The study population consisted of 2 groups of women who had previously been enrolled in a randomized clinical trial: group A was not treated, and group B was treated. All women were scheduled for follow-up visits every 6 months, or more frequently if symptoms arose. Microbiological evaluation was performed only in symptomatic women. All women were followed up for a mean of 38.8 months to analyze data from urine cultures and antibiograms. RESULTS The previous study population consisted of 673 women, but 123 did not attend the entire follow-up period. For the final analysis, 257 of the remaining 550 patients were assigned to group A, and 293 to group B. At the end of follow-up, the difference in recurrence rates was statistically significant (P < .001): 97 (37.7%) in group A versus 204 (69.6%) in group B. Isolated Escherichia coli from group B showed higher resistance to amoxicillin-clavulanic acid (P = .03), trimethoprim-sulfamethoxazole (P = .01), and ciprofloxacin (P = .03) than that from group A. CONCLUSIONS This study shows that AB treatment is associated with a higher occurrence of antibiotic-resistant bacteria, indicating that AB treatment in women with rUTIs is potentially dangerous.

Is adjuvant chemotherapy indicated in stage I pure immature ovarian teratoma (IT)? A multicentre Italian trial in ovarian cancer (MITO-9).

OBJECTIVE Conservative surgery followed by platinum-based chemotherapy is considered the standard approach for stage I immature ovarian teratoma (IT), except for stage IA G1. Nevertheless the use of chemotherapy in stage IA G2-3 and IB-IC is controversial. The aim of this study was to evaluate the outcome of patients with IT in order to define the role of chemotherapy in stage I disease. METHODS Twenty-eight patients with stage I IT treated in MITO centers were retrospectively reviewed. Grade, stage, age, surgical and postoperative treatment were analyzed using χ(2) test and T test looking for association with recurrence. RESULTS Median age was 25.5. Twenty-four patients underwent fertility-sparing surgery. FIGO stages were 19 IA, 2 IB, and 7 IC. Nine patients had grade 1 tumor, 12 grade 2, and 7 grade 3. Nine patients received adjuvant chemotherapy. Overall recurrence rate was 21.4% (2 in chemotherapy group and 4 in the group without treatment). No patients with G1 had recurrence, whereas 25% of G2 and 42.9% of G3 relapsed. Recurrence rate was not significantly different according to stage, grade or adjuvant chemotherapy, whereas it was greater in the group not operated in a MITO center, not staged and of age lower than 20 years, with statistical significance. At recurrence 4 patients presenting with mature teratoma were treated with surgery alone, whereas 2 recurring with IT were treated with surgery plus chemotherapy. After a median follow-up of 59 months all patients are NED. CONCLUSIONS Our study suggests that chemotherapy may be withheld for primary therapy and utilized only for recurrence.

Outcome and risk factors for recurrence in malignant ovarian germ cell tumors: a MITO-9 retrospective study.

Aims: This study aimed to investigate the outcome of patients with malignant ovarian germ cell tumors (MOGCTs) and to define the risk factors for recurrence. Methods: A total of 123 patients with MOGCTs were retrospectively reviewed among MITO centers. Eighty-one patients had primary treatment in a MITO center, whereas the other 42 were referred for adjuvant chemotherapy or recurrence. The clinicopathologic characteristics were evaluated for association with relapse or death. Results: Median age was 24 years (range, 11-76 years). Forty-nine (39.8%) had dysgerminomas, 35 (28.5%) had immature teratomas, 12 (9.8%) had mixed germ cell tumors, 26 (21.1%) had yolk sac tumors, and 1 (0.8%) had embryonal carcinoma. International Federation of Gynecology and Obstetrics stage distribution was as follows: stage I, 87 (70.7%); stage II, 3 (2.4%); stage III, 29 (23.6%); and stage IV, 4 (3.3%). Fertility-sparing surgery was performed in 92 patients, whereas the remaining 31 received radical surgery; 65.8% of patients received adjuvant chemotherapy. Recurrence rate was 17.8% and the median time to recurrence was 9 months. Univariate and multivariate analyses showed that patient age (>45 years) and treatment outside a referral (MITO) center were the most important predictors of recurrence. The 5-year overall survival rate was 88.8%, with a median follow-up of 61 months. Univariate and multivariate analyses demonstrated that stage greater than I and yolk sac tumors were independent poor prognostic indicators. Conclusions: This study confirms that MOGCTs have excellent prognosis, with 5-year overall survival rates of 95.6% and 73.2% in stage I and advanced stages, respectively. Age older than 45 years and treatment not in a referral center are independent risk factors for recurrence, whereas stage greater than I and yolk sac histology are independent poor prognostic indicators.

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.

The Influence of Adenomyosis in Patients Laparoscopically Treated for Deep Endometriosis

STUDY OBJECTIVE A strong association exists between adenomyosis and endometriosis and a common pathogenetic mechanism was proposed. The aim of this study was to evaluate whether and how the presence of concurrent adenomyosis can affect the outcome of laparoscopic excision of deep endometriosis. DESIGN Data were retrospectively collected from our computerized medical records (Canadian Task Force classification II-3). SETTING General hospital. INTERVENTION Restrospective evaluation. PATIENTS From January 2003 through July 2005, 40 consecutive patients affected by concomitant endometriosis and adenomyosis were included in group A and another 40 affected by endometriosis only were included in group B. MEASUREMENTS AND MAIN RESULTS In group A, 20 women required bowel surgery (17 segmental and 3 full-thickness discoid resections) versus 16 patients in the other group (13 segmental bowel resections with end-to-end anastomosis and 3 discoid resections). Dysmenorrhea and dyspareunia after treatment improved (p<.01) in both groups, whereas dyschezia improved only in group A. The persistence of menometrorrhagia was more frequent in group B (p<.01). During follow-up, patients of group A underwent medical treatment for a longer time than those of group B (p<.001). Clinical detection of endometriosis recurrence was more frequent in patients with adenomyosis (p<.01), whereas no difference existed in the incidence of the recurrence detected by ultrasound. The overall number of pregnancies after surgery was significantly lower in the group with adenomyosis (p=.03). CONCLUSION Complete excision of deep endometriosis is not always feasible because of adenomyosis. For this reason, preoperative imaging screening for adenomyosis could be included in the preoperative workup when extensive disease is clinically suspected.

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.

Robotic single-site hysterectomy: two institutions' preliminary experience.

To evaluate the feasibility, safety and peri‐ and postoperative outcomes of robotic single‐site hysterectomy for gynaecological diseases.