Cono Scaffa

Conservative treatment of early endometrial cancer: Preliminary results of a pilot study

OBJECTIVE This study evaluated the feasibility and efficacy of combined operative hysteroscopy (HSC) and hormone therapy as fertility-preserving treatment in a cohort of selected young women with early endometrial carcinoma (EC). METHODS Fourteen patients (median age 38 years, range 26-40) with FIGO stage IA (intramucous) EC wishing to preserve fertility were enrolled with the following inclusion criteria: age ≤40 years; no evidence of Lynch II syndrome; well-differentiated estrogen/progesterone receptor positive (ER+/PR+) endometrioid EC; no evidence of myoinvasion, multifocal tumor, node metastasis, ovarian mass; normal serum CA 125. Treatment consisted of hysteroscopic ablation of the lesion and the myometrial tissue below, followed by oral megestrol acetate (MA) 160 mg/day for 6 months (6 pts) or 52 mg levonorgestrel-medicated intrauterine device (LNG-IUD) for 12 months (8 pts). RESULTS With a median follow-up of 40 months (range 13-79), one patient recurred after 5 months from operative HSC and underwent definitive surgery, one patient showed an endometrial hyperplasia without atypia at the 3 and 6 month HSC control, with negative controls thereafter. Three patients have attempted to conceive and one of them conceived and term delivered a healthy baby. CONCLUSIONS Combined operative HSC and progestin therapy may have a role for safe and effective conservative management of early EC in selected patients wishing to preserve fertility.

Uterine papillary serous, clear cell, and poorly differentiated endometrioid carcinomas: A comparative study

Introduction: Uterine papillary serous and clear cell carcinomas (UPSCs/CCs) show a different spreading from that of poorly differentiated endometrioid carcinomas (PDECs) and are usually thought to be prognostically more aggressive than PDECs. On the contrary, it has been recently claimed that UPSC/CC and PDEC have a similar prognosis. In this retrospective study on 2 institutional databases, the surgical-pathological data and survival have been compared in patients with UPSC/CC and PDEC. Methods: A total of 139 surgically staged consecutive patients, 63 with UPSC/CC (37 UPSC; 26 CC) and 76 with PDEC clinically limited to the uterine corpus, have been compared for nuclear ploidy, myometrial invasion, (occult) cervical extension, peritoneal, and lymph node metastasis. Prognostic factors have been correlated through multivariate analysis with survival (disease-specific [DSS] and disease-free [DFS]). Results: Peritoneal metastases and aneuploidy were found to be the only parameters significantly different in the 2 groups: peritoneal metastases 28.6% in UPSC/CC (extrapelvic 19%) and 7.9% in PDEC (extrapelvic 2.6%) (P = 0.001), aneuploidy 48.6% in UPSC/CC and 30.6% in PDEC (P = 0.05). Five-year DSS was 57.9% versus 75.2% (P = 0.02), and DFS was 52.3% versus 71.4% (P = 0.04) for UPSC/CC and PDEC, respectively. All but cervical and lymph node involvement were significant predictors of survival. After multivariate analysis, histotype (DSS: hazard ratio [HR], 1.98; 95% confidence interval [CI], 1.02-3.86; P = 0.04; DFS: HR, 1.94; 95% CI, 1.04-3.63; P = 0.04), stage (DSS: HR, 2.26; 95% CI, 1.10-4.65; P = 0.03; DFS: HR, 2.21; 95% CI, 1.12-4.38; P = 0.02), and myometrial invasion (DSS: HR, 2.86; 95% CI, 1.22-6.69; P = 0.01; DFS: HR, 3.96; 95% CI, 1.63-9.62; P = 0.002) were independent risk factors for survival. Conclusions: Uterine papillary serous and clear cell carcinomas spread to abdominal peritoneum more frequently than PDEC; multivariate analysis confirms UPSC/CC as an independent, unfavorable predictor of outcome.

Clinical trials with pegylated liposomal Doxorubicin in the treatment of ovarian cancer.

Among the pharmaceutical options available for treatment of ovarian cancer, increasing attention has been progressively focused on pegylated liposomal doxorubicin (PLD), whose unique formulation prolongs the persistence of the drug in the circulation and potentiates intratumor accumulation. Pegylated liposomal doxorubicin (PLD) has become a major component in the routine management of epithelial ovarian cancer. In 1999 it was first approved for platinum-refractory ovarian cancer and then received full approval for platinum-sensitive recurrent disease in 2005. PLD remains an important therapeutic tool in the management of recurrent ovarian cancer in 2012. Recent interest in PLD/carboplatin combination therapy has been the object of phase III trials in platinum-sensitive and chemonaïve ovarian cancer patients reporting response rates, progressive-free survival, and overall survival similar to other platinum-based combinations, but with a more favorable toxicity profile and convenient dosing schedule. This paper summarizes data clarifying the role of pegylated liposomal doxorubicin (PLD) in ovarian cancer, as well as researches focusing on adding novel targeted drugs to this cytotoxic agent.

Long-term safety and efficacy of raloxifene in the prevention and treatment of postmenopausal osteoporosis: an update

The integrity of bone tissue and its remodeling that occurs throughout life requires a coordinated activity of osteoblasts and osteoclasts. The decreased estrogen circulating level during postmenopausal transition, with a prevalence of osteoclastic activity over osteoblastic activity, represents the main cause of bone loss and osteoporosis. Osteoporosis is a chronic disease requiring long-term therapy and it is important to evaluate the efficacy and safety of treatments over several years, as the fear of health risks is a common reason for discontinuing therapy. Raloxifene is a selective estrogen receptor modulator (SERM) leading to estrogen-agonist effects in some tissues and estrogen-antagonist effects in others. Raloxifene is effective to prevent and treat postmenopausal vertebral osteoporosis, with reduction of spine fractures and, in post-hoc analyses, non-spine fractures in high-risk subjects. Moreover, raloxifene reduces the risk of invasive breast cancer and improves the levels of serum lipoprotein but with an increased risk of venous thromboembolism and fatal stroke, without significant change in the incidence of coronary events. For these reasons the overall risk-benefit profile is favorable. Therefore, when considering the use of raloxifene in a postmenopausal woman, we should take into account the osteoporosis-related individual risk and weigh the potential benefits, skeletal and extra-skeletal, against the health risks.

Surgical Management of Early Cervical Cancer: The Shape of Future Studies

Early cervical cancer, in particular in the presence of favorable pathologic risk factors, accounts for a very low incidence of parametrial involvement and lymph node metastasis. This means that a less radical surgery may be an oncologically safe treatment in selected cases, with the aim of preserving fertility and/or reducing morbidity without compromising survival. The extensiveness of surgery has decreased relatively in recent decades, the “modified” radical hysterectomy still being the current gold standard by most international guidelines. Vaginal (or abdominal) radical trachelectomy, simple hysterectomy, or cervical conization has been proposed in association with pelvic lymphadenectomy. Sentinel lymph node mapping may be an option to avoid a complete pelvic lymphadenectomy. Ongoing research efforts are especially being made in properly identifying the patient subset suitable for a conservative/less radical approach and prospectively confirming the oncological safety of the proposed clinical–pathological algorithms.

Efficacy of adjuvant chemotherapy in early stage uterine leiomyosarcoma: A systematic review and meta-analysis

OBJECTIVE We sought to review the current evidence in order to test the efficacy of adjuvant chemotherapy in improving disease-free survival in patients affected by early stage uterine leiomyosarcoma. METHODS On July 2016, literature was searched in order to identify trials comparing different postoperative adjuvant strategies for patients diagnosed with early stage uterine leiomyosarcoma. RESULTS Our analysis included 360 patients: 145 (40%), 53 (15%), and 155 (43%) had chemotherapy (with or without radiotherapy), radiotherapy, and observation, respectively. Seven (2%) patients who had radiotherapy with or without chemotherapy were excluded from further analysis in order to reduce risk of biases. Administration of chemotherapy (with or without radiotherapy) did not improve outcomes in comparison to observation (OR: 0.79 (95%CI: 0.48, 1.29)), or radiotherapy (OR: 0.90 (95%CI: 0.42, 1.94)). Loco-regional recurrence rate was similar comparing patients undergoing chemotherapy (with or without radiotherapy) with having observation alone (OR: 0.84 (95%CI: 0.44, 1.60)). Similarly, pooled results suggested that chemotherapy administration did not affect distant recurrence rate in comparison to no chemotherapy (OR: 0.80 (95%CI: 0.50, 1.28)), and observation alone (OR: 0.99 (95%CI: 0.60, 1.64)). However, patients undergoing chemotherapy (with or without radiotherapy) experienced a trend towards lower risk of developing distant recurrences (OR: 0.49 (95%CI: 0.24, 1.03)) and a higher risk of developing loco-regional recurrences (OR: 3.45 (95%CI: 1.02, 11.73)) than patients undergoing radiotherapy. CONCLUSIONS In early stage uterine leiomyosarcoma, the role of adjuvant chemotherapy remains unclear. Owing to the high recurrence rate, even in the early stage of disease, further innovative therapeutic strategies have to be tested.

Secondary cytoreductive surgery for isolated lymph node recurrence of epithelial ovarian cancer: A multicenter study

INTRODUCTION Chemotherapy is the standard treatment of recurrent epithelial ovarian cancer (EOC), but its use in nodal relapses is still debated. On the other hand, the role of secondary cytoreductive surgery (SCS) remains controversial. Aim of this study is to evaluate feasibility and outcomes of SCS for the specific setting of recurrent ovarian cancer, exclusively relapsing in lymph nodes. PATIENTS AND METHODS We conducted a retrospective analysis in five Italian Institutions (University of Torino, INT of Milano, CRO of Aviano, University of Pisa and INT of Napoli) from 2000 to 2012. Patients with EOC who underwent secondary surgery for isolated lymph node recurrence (ILNR) were selected. RESULTS Seventy-three patients were identified. At first diagnosis, patients received debulking surgery and platinum-based chemotherapy. The median disease free interval from completion of primary chemotherapy to nodal recurrence was 18 months. Nodal recurrence was para-aortic in 37 patients (50.7%), pelvic in 21 (28.8%), pelvic and para-aortic in 9 (12.3%), pelvic and inguinal in 3 (4.1%) and inguinal in 3 (4.1%). During SCS, in 1 patients nephrectomy was necessary for renal vein injury. No significant postoperative morbidity occurred. Median follow-up is 50 months. After secondary surgery, 32 (43.8%) are alive without disease, 18 (24.6%) are alive with disease and 23 patients (31.5%) are dead of disease. Five-year overall survival from the time of treatment of recurrent disease is 64%. CONCLUSIONS Secondary surgery for ILNR of ovarian cancer is feasible, safe, with low morbidity and it is associated with a favorable outcome.

Lung cancer diagnosis on ovary mass: a case report

Metastatic neoplasms to the ovary often cause diagnostic problems, in particular those large ovarian masses mimicking primary tumors. Most of these tumors arise from digestive system or breast, while 37-year-old woman diagnosed as right adnexal complex mass, with a subpleural nodule in the apical part of the left lower lobe, at preoperative chest computed tomography scan. The patient underwent total abdominal hysterectomy with right salpingo-oophorectomy (ovarian mass 220 × 200 mm), total omentectomy, left ovarian biopsy, peritoneal random biopsies, and peritoneal washings for cytology. Pathologic and immunohistochemical examination of ovarian specimen suggested morphology and expression of metastatic lung adenocarcinoma with an intense positivity for Thyroid Transcriptional Factor-1 (TTF-1) and Cytokeratin 7 (CK7) staining. Fine needle biopsy of the lung nodule found epithelioid like malignant cells, confirming the diagnosis of an ovarian metastasis from a primary lung cancer.This report focused on the clinical and pathologic diagnostic challenge of distinguishing secondary from primary ovarian neoplasms. Issues on useful immunohistochemical stains are also discussed.

Incorporating 3D laparoscopy for the management of locally advanced cervical cancer: a comparison with open surgery.

Purpose To test the effects of the implementation of 3D laparoscopic technology for the execution of nerve-sparing radical hysterectomy. Methods Thirty patients undergoing nerve-sparing radical hysterectomy via 3D laparoscopic (3D-LNSRH, n = 10) or open surgery (NSRH, n = 20) were studied prospectively. Results No significant differences were observed in baseline patient characteristics. Operative times were similar between groups. We compared the first 10 patients undergoing 3D-LNSRH with the last 20 patients undergoing NSRH. Baseline characteristics were similar between groups (p>0.2). Patients undergoing 3D-LNSRH had longer operative time (264.4 ± 21.5 vs 217.2 ± 41.0 minutes; p = 0.005), lower blood loss (53.4 ± 26.1 vs 177.7 ± 96.0 mL; p<0.001), and shorter length of hospital stay (4.3 ± 1.2 vs 5.4 ± 0.7 days; p = 0.03) in comparison to patients undergoing open abdominal procedures. No intraoperative complication occurred. One (10%) patient had conversion to open surgery due to technical difficulties and the inability to insert the uterine manipulator. A trend towards higher complication (grade 2 or worse) rate was observed for patients undergoing NSRH in comparison to 3D-LNSRH (p = 0.06). Considering only severe complications (grade 3 or worse), no difference was observed (0/10 vs 2/20; p = 0.54). Conclusions 3D-laparoscopic nerve-sparing radical hysterectomy is a safe and effective procedure. The implementation of 3D laparoscopic technology allows the execution of challenging operations via minimally invasive surgery, thus reducing open abdominal procedure rates. Further large prospective studies are warranted.

The association of pre-treatment HPV subtypes with recurrence of VIN

OBJECTIVE To assess whether pre-treatment HPV types are associated with recurrence of high-grade vulvar intraepithelial neoplasia (VIN2+). STUDY DESIGN Data of consecutive patients with pretreatment HPV DNA test undergoing treatment for VIN2+ were retrospectively collected. Risk factors promoting the risk of VIN2+ persistence and recurrence were analyzed using Kaplan-Meier and Cox hazard proportional models. RESULTS 64 patients had pretreatment vulvar-vaginal HPV DNA test. Two were excluded due to the presence of synchronous vulvar cancer, thus leaving 62 patients for the final analysis. HPV16, HPV18, HPV31 and HPV33 were the most common HPV genotype detected, occurring in 15 (24.2%), 4 (6.5%), 8 (12.9%) and 5 (8.0%) patients, respectively. HPV was not detected in 19 (30.6%) patients. During a mean (SD) follow up of 56.7 (±26.7) months, 10 (16.1%) patients had VIN2+ persistence/recurrence. Mean (SD) lesion-free interval was 51.7 (±31.4) months. Via multivariate analysis, pretreatment infection from HPV31 (HR:46.7(95%CI:4.21,518.4); p=0.02) and HPV33 (HR:77.0(95%CI:6.73,881.9); p<0.001) correlated with an increased risk of VIN2+ persistence/recurrence. Additionally, we observed that patients undergoing surgical excision followed by LASER ablation experienced a trend towards lower recurrence rate than patients undergoing other surgical or medical treatments (HR:0.20(95%CI:0.03,1.09); p=0.05). Two (3.2%) patients developed progression to vulvar cancer. CONCLUSIONS Owing to the inherent biases of the retrospective study design and the small sample size, our data have to be corroborated by larger and prospective studies. HPV31 and HPV33 have a potential role in predicting VIN2+ persistence/recurrence. These findings will be paramount, owing to the implementation of new immunization programs.