Stefania Chiari

Behavior of Borderline Tumors With Particular Interest to Persistence, Recurrence, and Progression to Invasive Carcinoma: A Prospective Study

PURPOSE Borderline tumors account for 10% to 20% of epithelial ovarian tumors, and their prognosis is outstanding; nevertheless, a mortality of up to 20% has been reported, particularly in earlier reports. There is a lack of information about the actual mortality and the rate of progression into invasive carcinoma in large and prospectively accrued populations. PATIENTS AND METHODS All women with borderline ovarian tumors undergoing primary surgery in our department or referred within 3 months from surgery performed elsewhere from 1982 to 1997 were prospectively accrued and observed. RESULTS We studied 339 women (83.4% stage I, 7.9% stage II, and 8.5% stage III). The median age at diagnosis was 39 years. A total of 150 women underwent radical surgery, and 189 underwent fertility-sparing surgery. After surgery, 13 women had macroscopic residual disease. With a median follow-up of 70 months, 317 women are alive with no clinical disease (eight with documented subclinical persistence of implants), three are alive with clinical disease, two died of disease, 10 died of other reasons, and seven women have been lost to follow-up. The recurrence of disease was higher after fertility-sparing surgery (35 of 189 cases) than after radical surgery (seven of 150 cases); nevertheless, all but one woman with recurrence of borderline tumor or progression to carcinoma after conservative surgery were salvaged. We observed seven progressions (2.0%) into invasive carcinoma, five in serous tumors (2.4%), and two in mucinous tumors (1.6%). The disease-free survival is 99.6% in stage I patients, 95.8% in stage II, and 89% in stage III. CONCLUSION The survival of patients with borderline tumors is higher than previously described in some retrospective studies. Conservative surgery is safe and may be proposed to several patients with early and disseminated disease after thorough discussion of all therapeutic options. Progression to carcinoma is approximately 2% and may be observed in both mucinous and serous tumors.

Conservative surgery for Stage I ovarian carcinoma in women of childbearing age

Objective To assess the results of a policy of tailored conservative surgical management for young women with stage I ovarian carcinomas.

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 <or=3 cm, aged <or=40 years with no uterine and lymphnode neoplastic involvement were evaluated. Three courses with cisplatin 75 mg/m(2), paclitaxel 175 mg/m(2) and ifosfamide 5 g/m(2) (epirubicin 80 mg/m(2) in adenocarcinoma) were followed by cold-knife conization and pelvic lymphadenectomy. When intraoperative frozen section revealed massive neoplastic cervical persistence a radical total hysterectomy was performed. RESULTS Thirty women (59%) did not accept the conservative approach. In the remaining 21 patients median age was 30 years and median tumor size was 15 mm (range 10-30 mm). Adenocarcinoma was present in 12 cases (57%) and indifferentiated neoplasia in 10 (48%). Following neoadjuvant treatment, pathological complete response was observed in 5 cases, in situ or microinvasive residue in 12 and stromal invasion >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.

Surgical management of malignant ovarian germ-cell tumors: 10 years' experience of 129 patients

Objective To evaluate the surgical management of ovarian germ-cell tumors treated at a single institution during the last decade. Methods One hundred twenty-nine patients affected by ovarian germ-cell tumors were studied retrospectively for their surgical management. Fifty-seven patients were affected by dysgerminoma, 39 by non-dysgerminoma, and 33 by pure immature teratoma. Seventy-nine patients were stage I according to International Federation of Gynecology and Obstetrics criteria, with five first referred at recurrence, 11 at stage II, 35 at stage III, and four at stage IV. Results Fertility-sparing surgery was performed in 108 of 129 patients. Eighty-five of 100 referred patients underwent surgical or radiologic restaging, with an increase in staging in 16 cases. Three patients with immature teratoma underwent second laparotomy for a growing mass. Thirty-one patients underwent second-look surgery, with positive findings in four cases. Three patients did not respond to chemotherapy, and ten had a recurrence after complete response or surveillance. Six patients died of tumor, with an overall survival of 96% (mean follow-up time 55 months). Conclusion Fertility-sparing surgery is warranted in all ovarian germ-cell tumors because it does not affect recurrence rate or survival. Extensive tumor-reductive surgery is advisable only in immature teratoma patients and is not necessary for other histologic types. Restaging can be useful in selected cases, but the administration of effective chemotherapy, when needed, seems to be more important. The usefulness of second-look surgery is marginal.

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.

Conservative treatment followed by chemotherapy with doxorubicin and ifosfamide for cervical sarcoma botryoides in young females

SummarySarcoma botryoides of the cervix is an extremely rare tumour and seems to be associated with a better prognosis than its vaginal counterpart. Recent studies have suggested that it is possible to limit surgery to local excision in stage I cases. We report three cases of young subjects treated successfully with polypectomy or diathermy loop excision followed by adjuvant chemotherapy. One patient had a local recurrence which was treated with further local excision. All subjects remain alive without evidence of recurrence and with normal menstrual function 36, 38 and 38 months following initial diagnosis. A conservative surgical approach to early cervical sarcoma botryoides is possible. The efficacy of adjuvant chemotherapy and the regimen of choice still need to be investigated.

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 (γ = 0.49 and 0.41, respectively) as compared to HPV‐18 and ‐33 group (γ = 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. J. Med. Virol. 81:278–287, 2009.

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.

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.

DR antigen expression on ovarian carcinoma cells does not correlate with their capacity to elicit an autologous proliferative response

SummaryExpression of HLA-DR antigens by purified preparations of human ovarian carcinoma cells freshly isolated from surgical specimens was examined in parallel with the capacity of tumor cells to elicit a blastogenic response from autologous lymphocytes in mixed lymphocyte-tumor culture (MLTC) assay. Of 21 tumor preparations, 11 (52%) reacted with monoclonal antibodies 279 and/or 949 specific for a monomorphic determinant of HLA-DR antigens, with heterogeneous positivity, ranging between 30% and 95%. In this series of patients positive MLTC occurred in 8/21 individual experiments. The HLA-DR expression was proportionally similar in tumors giving positive MLTC (4/8=50%) and negative MLTC (7/13=53%). The lack of correlation between DR expression on tumor cells and stimulatory activity in autologous MLTC and the fact that DR-negative tumors could induce lymphocyte stimulation, support the hypothesis that blastogenesis occurs upon recognition of tumor-associated antigens, different from DR molecules, possibly tumor-specific antigens.