Long-term results of fertility-sparing treatment compared with standard radical surgery for early-stage epithelial ovarian cancer.

BACKGROUND: The objective of this study is to evaluate the safety of fertility-sparing surgery (FSS) for early-stage epithelial ovarian cancer (EOC). METHODS: A retrospective analysis was performed to identify patients treated for early-stage EOC and to compare the clinical outcomes of patients treated with FSS and radical surgery (RS). RESULTS: A total of 1031 patients were treated at two Institutions, 242 with FSS (group A) and 789 with RS (group B). Median duration of follow-up was 11.9 years. At univariate analyses, FSS was associated with decreased risk of relapse (P=0.002) and of tumour-related death (P=0.001). Multivariate analysis did not confirm the independent positive role of FSS neither on relapse-free interval (RFI) nor on cancer-specific survival (CSS). Tumour grade was associated with shorter RFI (P<0.001) and shorter CSS (P=0.001). The type of treatment did not influence CSS or RFI in any grade group. We also found a significant association between low-grade tumours and younger age. CONCLUSIONS: Fertility-sparing surgery is an adequate treatment for patients with stage I EOC. The clinical outcome of patients with G3 tumours, which is confirmed to be the most important prognostic factor, is not determined by the type of treatment received.

Long-Term Clinical Benefits of Neoadjuvant Chemotherapy in Women With Locally Advanced Cervical Cancer: Validity of Pathological Response as Surrogate Endpoint of Survival.

OBJECTIVE: Neoadjuvant chemotherapy (NACT) is a valid treatment option for women with locally advanced cervical cancer (LACC). This study aims to evaluate the impact of sociodemographic factors, clinical factors, and NACT regimens on survival endpoints. The role of pathological response to NACT as a surrogate endpoint of survival was also assessed. MATERIALS AND METHODS: Retrospective analysis of consecutive sample data from women with LACC (stages Ib2-IVa) who underwent NACT followed by radical surgery was performed. Response was classified as optimal response (including complete response and optimal partial response), suboptimal partial response, stable disease, and progressive disease. RESULTS: Four hundred forty-six women who had undergone surgery from 1992 to 2011 were analyzed. The overall optimal response was 35.4%. At a median follow-up of 12.7 years, 165 women (37.0%) experienced recurrence or died. Increase in patient age at surgery, International Federation of Gynecology and Obstetrics stage III/IV versus stage Ib2, and lymph-node positivity versus negativity seemed to impact negatively on survival, whereas neoadjuvant platinum-Taxol-containing regimens (compared with platinum-based regimens) improved survival. Response to NACT could be considered a surrogate endpoint of survival. CONCLUSIONS: Age, International Federation of Gynecology and Obstetrics stage III/IV, lymph-node involvement, and type of NACT administered have a significant impact on survival. Response to NACT is a good surrogate endpoint of survival in patients with LACC.

Tidal expiratory flow limitation at rest as a functional marker of pulmonary emphysema in moderate-to-severe COPD.

BACKGROUND: Tidal expiratory flow limitation (EFL) is a step of paramount importance in the functional decline in COPD. Among mechanisms contributing to EFL, loss of airway-parenchymal interdependence could mostly be involved. AIM: To assess if EFL is a functional marker more frequently linked to prevalent pulmonary emphysema rather than to prevalent chronic bronchiolitis in COPD patients with moderate-to-severe airflow obstruction. METHODS: Forty consecutive stable COPD patients with FEV1 between 59 and 30% of predicted were functionally evaluated by measuring spirometry, maximal flow-volume curve and lung diffusion capacity (DLCO) and coefficient of diffusion (KCO). EFL was assessed by the negative expiratory pressure (NEP) method both in sitting and supine position. Chronic dyspnea was also scored by modified Medical Research Council (mMRC) scale. RESULTS: In sitting position 13 patients (33%) were flow limited (FL) and 27 were non-flow limited (NFL). Only FEV1/FVC, FEV1 and MEF25-75% were different between FL and NFL patients (p < 0.01). In supine position, however, among NFL patients in sitting position those who developed EFL, had significantly lower values of DLCO and KCO (p < 0.05) and higher mMRC score (p < 0.01), but similar values of FEV1 as compared to those who did not have EFL. CONCLUSIONS: In COPD EFL in sitting position is highly dependent by the severity of airflow obstruction. In contrast, the occurrence of EFL in supine position is associated with worse DLCO and KCO and greater chronic dyspnea, reflecting a prevalent emphysematous phenotype in moderate-to-severe COPD patients.

Dynamic pulmonary hyperinflation occurs without expiratory flow limitation in chronic heart failure during exercise.

To assess the occurrence of tidal expiratory flow limitation (EFL) and/or dynamic pulmonary hyperinflation (DH) in chronic heart failure (CHF) during exercise 15 patients with stable systolic CHF, aged 69 ± 6yr, underwent pulmonary function testing and incremental cardio-pulmonary exercise testing. They subsequently performed constant load exercise testing at 30, 60 and 90% of respective maximum workload. At each step the presence of EFL, by negative expiratory pressure technique, and changes in inspiratory capacity (IC) were assessed. Ejection fraction amounted to 36 ± 6% and VO2, peak (77 ± 19% pred.) was reduced. EFL was absent at any step during constant load exercise. In 6 patients IC decreased more than 10% pred. at highest step. Only in these patients TLC, FRC, RV FEF(25-75%) and DL(CO) were decreased at rest. VO2, peak correlated with DL(CO), TLC and IC at rest and with IC (r(2)=0.59; p<0.001) and decrease in IC (r(2)=0.44; p<0.001) at 90% of maximum workload. During exercise CHF patients do not exhibit EFL, but some of them develop DH that is associated with lower VO2, peak.

Delivery delay with neoadjuvant chemotherapy for cervical cancer patients during pregnancy: a series of nine cases and literature review.

OBJECTIVE: Treatment of locally invasive cervical cancer diagnosed during pregnancy in women who desire to retain their pregnancy is a major challenge to physicians. Neoadjuvant chemotherapy followed by radical hysterectomy has been reported to be an attractive option to delay delivery until fetal viability has been reached. METHODS: Between 1994 and 2009 9 patients were treated at San Gerardo Hospital (Monza, Italy) for cervical cancer during pregnancy. RESULTS: FIGO stage was IB1 in four patients and IB2 in five. Tumor diameter ranged between 20 and 70 mm. After neoadjuvant platinum-based chemotherapy partial response was achieved in 5 patients, while 4 had a stable disease. One patient received a second-line chemotherapy during pregnancy due to progressive disease, achieving a partial response. Median duration of therapy delay until cesarean section was 16 weeks. Between 30 and 36 weeks of gestation all patients underwent cesarean section. Piver II radical hysterectomy with pelvic lymphadenectomy was performed. Two children had mild perinatal morbidities and were discharged in good conditions after 14 and 40 days. Three patients received adjuvant therapy for pathological risk factors. Four patients relapsed (44%) and two of them (23%) died because of tumor progression. CONCLUSION: During pregnancy, the oncological outcome of cervical cancer patients is similar to non-pregnant ones. Chemotherapy does not seem to affect fetal health and development, even if longer follow-up is required. Therefore, neoadjuvant chemotherapy for the treatment of locally invasive cervical cancer during pregnancy seems to be a reasonable option for delay definitive treatment until fetal viability is obtained.

Effect of preceding inspiratory speed and end-inspiratory pause on forced expiratory manoeuvre in healthy subjects and chronic obstructive pulmonary disease patients.

BACKGROUND: Lower peak expiratory flow (PEF) and forced expiratory volume in 1 s (FEV(1)) have been consistently found after slow inspiration with end-inspiratory pause (EIP). OBJECTIVES: It was the aim of this study to establish the respective influence of the speed of preceding inspiration (SPI) and EIP on the parameters obtained from the following expiratory forced vital capacity (FVC) manoeuvre. METHODS: In 8 healthy subjects and 12 patients with chronic obstructive pulmonary disease (COPD), a number of inspirations with different SPI and EIP were performed. In the subsequent FVC manoeuvre, maximal expiratory flows, including PEF, and maximal expired volumes at different times, including FEV(1), were measured. For each FVC manoeuvre, peak expiratory time, expired volume at PEF (as % of FVC), flow limitation by the negative expiratory pressure technique and FVC were checked to be sure of achieving a similar expiratory effort and starting inflation lung volume. RESULTS: The highest values of PEF and FEV(1) were found in normal subjects and COPD patients after fastest SPI without EIP (p < 0.001). In normal subjects, no significant PEF and FEV(1) changes during FVC manoeuvre were observed with different SPI, in the absence of EIP. In contrast, inspirations with slower SPI (inspiratory time >2 s) without EIP were followed by lower PEF in COPD patients (p < 0.05). As compared with inspirations without EIP, those with a presence of EIP were invariably followed by lower PEF and FEV(1), both in normal subjects and in COPD patients (p < 0.05). CONCLUSIONS: The effect of SPI on subsequent PEF and FEV(1) is irrelevant in healthy subjects as well as in COPD patients, unless SPI is too slow (inspiratory time >2 s), while any EIP decreases these indices in all individuals.

Prevalence and viral load of oncogenic human papillomavirus types associated with cervical carcinoma in a population of North Italy.

A cross-sectional study was carried out in a population of North Italy to determine the prevalence of eight oncogenic human papillomavirus (HPV) types most commonly found in cervical carcinoma and to study the relationship between HPV DNA loads and severity of disease. A total of 597 cervical samples obtained from patients with pathological findings (n = 472) and from women with normal cytology (n = 125) were analyzed by means of normalized Real-time PCR assays to quantify HPV-16, -18, -31, -45, and -33 group (including -33, -52, -58, -67); the normalization of oncogenic HPV viral load was carried out by quantitation of a single copy gene. The two most common oncogenic HPV types found were 16 and 31 (24.3% and 22.9% of pathological samples, respectively); multiple infections were demonstrated in 22% of pathological samples. Overall, the HPV total viral load was found to increase with increasing severity of associated lesions, although a stronger association was observed only for HPV-31 and HPV-16 (gamma = 0.49 and 0.41, respectively) as compared to HPV-18 and -33 group (gamma = 0.19 and 0.02, respectively). However, we found that high levels of HPV-31 or 33 group DNA could be prognostic of minor oncogenic risk for high-grade squamous intraepithelial lesions (H-SIL) (age adjusted odds ratio [AORs] = 1.57 and 1.26, respectively) than HPV-16 and HPV-18 (AORs = 30 and 8, respectively). The AORs also increased with HPV total viral load and reached a maximum of AORs = 15.7. Thus, HPV load is a type-dependent risk marker for the development of H-SIL.

Neoadjuvant chemotherapy and conservative surgery for stage IB1 cervical cancer.

OBJECTIVES: To assess the effectiveness of chemo-surgical conservative therapy for stage IB1 cervical tumors in patients desiring to preserve fertility. METHODS: From 1995 to April 2007 51 nulliparous patients with tumor 3 mm in 4. Four women deemed ineligible for conservative surgery after chemotherapy and one refusing to preserve her genital apparatus underwent radical hysterectomy. After a median follow-up of 69 months no relapses were observed. Nine women attempted to conceive: ten pregnancies occurred in 6 patients and 9 live babies have been born, while one woman experienced a first-trimester miscarriage. CONCLUSIONS: The high rate of pathological response confirms the effectiveness of the preoperative treatment for reducing the tumor volume allowing the removal only of a cervical cone instead of the entire cervix with cardinal ligaments as needed by radical trachelectomy. Successful pregnancies are possible after such integration.

Are borderline tumors of the ovary safely treated by laparoscopy?

OBJECTIVES: To evaluate the risk of the laparoscopic approach to patients with borderline ovarian tumors compared to the laparotomic management. METHODS: We treated or followed in our institution 479 women with borderline ovarian tumor. Sixty-two patients had fertility-sparing surgery followed by restaging or follow-up intervention: 30 operated by laparoscopy, 32 by laparotomy. Restaging surgery was performed in five cases and second-look surgery in 57. RESULTS: The diameter of the cyst is significantly lower in patients treated by laparoscopy, especially in women who underwent cystectomy (4.7 cm) compared to oophorectomy (10 cm, P = 0.008). Rupture of the cyst and stage IC were more frequent in the laparoscopic group. After a median follow-up of 61 months for the laparoscopic group and 77 months for the laparotomic group, we observed 11 patients (37%) with persistent disease after primary laparoscopy (adnexa, five cases; peritoneal implants, three cases; both patterns, three cases). After primary laparotomy, no patients showed early persistence of tumor, and ovarian relapses were diagnosed in seven women (22%) 33-138 months after laparotomy. The univariate analysis for the risk of neoplastic persistence after primary laparoscopy shows that patients with cysts greater than 5 cm have a higher risk (odds ratio 9.7, P = 0.02) compared to smaller cysts. No other factors proved significant, but the odds ratios for patients with serous tumor (5.8), stage IC (2.0), and those undergoing cystectomy (1.9) suggest a relationship to the probability of persistence. CONCLUSION: Laparoscopic treatment in borderline ovarian tumors should be reserved to masses not greater than 5 cm. When conservative therapy is desired, the entire affected ovary should be removed. If the neoplasia is bilateral, cystectomy could be allowed in women who wish to preserve fertility, although they are at high risk of relapse.

International Collaborative Ovarian Neoplasm trial 1: a randomized trial of adjuvant chemotherapy in women with early-stage ovarian cancer.

BACKGROUND: The question of whether platinum-based adjuvant chemotherapy can improve outcomes in patients with early-stage epithelial ovarian cancer is an important one. We carried out a multicenter, open randomized trial to determine whether adjuvant chemotherapy would improve overall survival and prolong recurrence-free survival in women with early-stage epithelial ovarian cancer. METHODS: Between August 1991 and January 2000, 477 patients in 84 centers in five countries were randomly assigned to receive either adjuvant chemotherapy immediately following surgery (n = 241) or no adjuvant chemotherapy until clinically indicated (n = 236). Kaplan-Meier curves of overall survival and recurrence-free survival were compared using the Mantel-Cox version of the log-rank test. All statistical tests were two-sided. RESULTS: Women who received adjuvant chemotherapy had better overall survival than women who did not (hazard ratio [HR] of 0.66, 95% confidence interval [CI] = 0.45 to 0.97; P =.03). These results translate into 5-year survival figures of 70% for women who did not receive adjuvant chemotherapy and 79% for women who did receive adjuvant chemotherapy, a difference of 9% (95% CI = 1% to 15%). Adjuvant chemotherapy also improved recurrence-free survival (HR = 0.65; 95% CI = 0.46 to 0.91; P =.01). These results translate into 5-year recurrence-free survival figures of 62% for women who did not receive adjuvant chemotherapy and 73% for women who did receive adjuvant chemotherapy, a difference of 11% (95% CI = 3% to 18%). CONCLUSION: These results suggest that platinum-based adjuvant chemotherapy improves survival and delays recurrence in patients with early-stage ovarian cancer.