Ultrasonographic diagnosis of adnexal masses: interobserver agreement in the interpretation of videos, using IOTA terminology.

OBJECTIVES: Aim of this study is to estimate interobserver agreement in classifying adnexal tumors using IOTA terms, simple rules and subjective assessment. In addition, we related observers' accuracy with their experience in gynecological ultrasonography and the year of IOTA certification. METHODS: Eleven observers with three different levels of experience evaluated videoclips of 70 adnexal masses, defining tumor type according to IOTA terms and definitions, classifying the mass using IOTA Simple rules and Subjective assessment as well as providing Color Score evaluation. Sensitivity, specificity and area under the ROC curve were calculated and the year of IOTA certification was related with operators' accuracy through Pearson correlation coefficient. Interobserver agreement was estimated calculating percentage of agreement, Fleiss kappa and Cohen's kappa. RESULTS: We found a positive correlation between the year of IOTA certification and operators' accuracy (Pearson coefficient 0.694), especially among the observers with the least experience, the residents (p = 0.003). For tumor type classification, identification of papillary projections and classification of tumors using subjective assessment, agreement among all observers was moderate (Fleiss kappa 0.455, 0.552, and 0.476, respectively) and increased with the years of experience. Agreement in the application of Simple Rules was moderate in all examiners with IOTA certification, with Fleiss kappa in the range of (0.403, 0.498). For Color Score assignment interobserver agreement among all observers was fair (Cohen's kappa 0.380). CONCLUSIONS: Even among expert examiners, the results of adnexal lesion assessment can be inconsistent. Experience impacts on accuracy and agreement in subjective assessment, while the application of Simple Rules can mitigate the role of experience in interobserver agreement. The knowledge of IOTA models among residents seams to improve their diagnostic accuracy, showing the benefits of IOTA terminology for in training sonographers.

The Risk of Recurrence in Endometrial Cancer Patients with Low-Volume Metastasis in the Sentinel Lymph Nodes: A Retrospective Multi-Institutional Study.

The aim of this study was to assess the impact of low-volume metastasis (LVM) on disease-free survival (DFS) in women with apparent early-stage endometrial cancer (EC) who underwent sentinel lymph node (SLN) mapping. Patients with pre-operative early-stage EC were retrospectively collected from an international collaboration including 13 referring institutions. A total of 1428 patients were included in this analysis. One hundred and eighty-six patients (13%) had lymph node involvement. Fifty-nine percent of positive SLN exhibited micrometastases, 26.9% micrometastases, and 14% isolated tumor cells. Seventeen patients with positive lymph nodes did not receive any adjuvant therapy. At a median follow-up of 33.3 months, the disease had recurred in 114 women (8%). Patients with micrometastases in the lymph nodes had a worse prognosis of disease-free survival compared to patients with negative nodes or LVM. The rate of recurrence was significantly higher for women with micrometastases than those with low-volume metastases (HR = 2.61; p = 0.01). The administration of adjuvant treatment in patients with LVM, without uterine risk factors, remains a matter of debate and requires further evaluation.

Gynecological Cancers in Lynch Syndrome: A Comparison of the Histological Features with Sporadic Cases of the General Population.

Introduction: About 5% of endometrial cancers (ECs) are attributed to an inherited predisposition, for which Lynch syndrome (LS) accounts for the majority of cases. Women with LS have a 40−60% predicted lifetime risk of developing EC, in addition to a 40−80% lifetime risk of developing colorectal cancer and other cancers. In this population, the lifetime risk of developing ovarian cancer (OC) is 10−12%. Object: to compare the histopathological features of LS-associated EC and OC with sporadic cancers in order to evaluate whether there are differences in terms of age at diagnosis, site of occurrence in the uterus, histological type, stage at diagnosis, and tumor grading. Materials and methods: we compared data obtained from 96 patients with LS-associated gynecological cancers (82 with EC and 14 with OC) to a control group (CG) of 209 patients who developed sporadic EC, and a CG of 187 patients with sporadic OC. Results: The mean age at diagnosis of LS-associated EC and OC was much lower than in the control groups. In both groups with EC, the endometrioid histotype was the most frequently occurring histotype. However, among LS women there was a significantly higher incidence of clear cell tumors (11% versus 2.4% in the CG, p = 0.0001). Similar to the sporadic cancer cases, most of the LS-associated ECs presented at an early stage (89% of cases at FIGO I-II stage). In the LS group, the tumor frequently involved only the inner half of the endometrium (77% of cases, p < 0.01). In the LS group, 7.3% of ECs were localized to the lower uterine segment (LUS), whereas no cancer developed in the LUS in the CG. No serous OCs were diagnosed in the LS group (versus 45.5% in the CG, p = 0.0009). Most of the LS-associated OCs presented at an early stage (85% of cases at FIGO I-II stages, p < 0.01). Conclusion: LS-associated EC and OC seem to have peculiar features, occurring at a younger age and at an earlier stage. In LS, EC less frequently involves the outer half of the endometrium, with a more frequent occurrence in the LUS. The presence of clear cell EC was more frequently observed, whereas in OC, the predominant histotype was endometrioid.

Low-Pressure Laparoscopy Using the AirSeal System versus Standard Insufflation in Early-Stage Endometrial Cancer: A Multicenter, Retrospective Study (ARIEL Study).

The aim of our study was to evaluate the benefits of a low-pressure insufflation system (AirSeal) vs. a standard insufflation system in terms of anesthesiologists' parameters and postoperative pain in patients undergoing laparoscopic surgery for early-stage endometrial cancer. This retrospective study involved five tertiary centers and included 152 patients with apparent early-stage disease who underwent laparoscopic surgical staging with either the low-pressure AirSeal system (8−10 mmHg, n = 84) or standard laparoscopic insufflation (10−12 mmHg, n = 68). All the intraoperative anesthesia variables evaluated (systolic blood pressure, end-tidal CO2, peak airway pressure) were significantly lower in the AirSeal group. We recorded a statistically significant difference between the two groups in the median NRS scores for global pain recorded at 4, 8, and 24 h, and for overall shoulder pain after surgery. Significantly more women in the AirSeal group were also discharged on day one compared to the standard group. All such results were confirmed when analyzing the subgroup of women with a BMI >30 kg/m2. In conclusion, according to our preliminary study, low-pressure laparoscopy represents a valid alternative to standard laparoscopy and could facilitate the development of outpatient surgery.

Neoadjuvant Chemotherapy Prior Fertility-Sparing Surgery in Women with FIGO 2018 Stage IB2 Cervical Cancer: A Systematic Review.

Nowadays, the optimal management of patients with cervical cancers measuring 2-4 cm desiring to maintain fertility is still uncertain. In this systematic review, we assessed the reliability of neoadjuvant chemotherapy (NACT) prior to fertility-sparing (FS) surgery in International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IB2 cervical cancer, in terms of pathologic response, oncological and obstetric outcomes. The review of the literature was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data, using MEDLINE and PubMed, were searched for from 1 January 2005 up to 1 December 2020. We identified 20 articles and 114 women with IB2 disease, possible candidates for NACT prior to FS surgery. However, uterine conservation was achieved only in 76.7% of them. Patients reached optimal pathological response to NACT in 60.9% of cases and a TIP (cisplatin, ifosfamide and paclitaxel) regime was related to the best response. Suboptimal response to NACT appeared to be an independent negative prognostic factor. Up to 9.2% of patients recurred with a median 7.4-months DFS, and 4.6% of patients died of disease. Fifty percent of women tried to conceive after treatment and NACT prior to conization appeared to be the most promising alternative to upfront radical trachelectomy in terms of obstetric outcomes. In conclusion, NACT prior to FS surgery is an option, but the literature about this issue is still weak and FS should be carefully discussed with patients.

Could a 2D/3D US based model be helpful in the assessment of myometrial invasion at time of intraoperative frozen section? A pilot study.

BACKGROUND: The assessment of myometrial invasion is a pivotal step in the preoperative staging of endometrial cancer. Intraoperative frozen section (FS) represents a reliable tool in directing surgeon's choices. Preoperative transvaginal ultrasound (US) showed high accuracy in evaluating myometrial invasion. This study aimed to understand if the application of a standardized ultrasonographic protocol for the pre-operative evaluation of myometrial invasion can help pathologists in improving the accuracy of FS. Furthermore, the agreement between US and FS in the assessment of myometrial invasion was assessed. METHODS: Sixty-six patients who underwent surgery for endometrial cancer were analyzed. Preoperative 2D/3D ultrasound was performed in all the patients. Myometrial invasion was estimated by subjective assessment and objective measurement techniques. Data from US were reported to pathologists through a prefilled form with depth and site of the maximum myometrial invasion. Diagnostic performance of US and FS were compared having the definitive histological examination as the gold standard. RESULTS: Influenced by the information given by our 3D US-model, FS showed a 90% sensitivity and a 93% specificity, with a 93% PPV and an 89% NPV. The agreement with histology was strong (K=0.824). Myometrial invasion was missed at the level of the isthmus by FS just in one case. Subjective assessment was confirmed as the most reliable ultrasonographic technique in assessing myometrial invasion, with 90% sensitivity, 78% specificity, 80% PPV and 89% NPV. The agreement with histology was substantial (K=0.68). CONCLUSIONS: The application of a preoperative 2D/3D US assessment would seem to help pathologists in detecting myometrial invasion in difficult areas of the uterus such as the isthmus, reducing downstaging and overtreatment.

Potential impact of introducing a nonavalent HPV vaccination.

OBJECTIVE: To test the theoretical utility of incorporating nonavalent vaccination against HPV into a clinical setting. METHODS: The present retrospective study included data from consecutive patients who underwent HPV-DNA testing between January 1, 1998, and December 31, 2015. Changes in the prevalence of different HPV types were assessed during three periods (T1, 1998-2003; T2, 2004-2009; and T3, 2010-2015) using XY analysis. RESULTS: The study included a total of 13 665 patients. Overall, 1361, 5130, and 7174 patients were included in the T1, T2, and T3 periods, respectively. The quadrivalent vaccine would have potentially protected against HPV in 71.5% (973/1361), 46.5% (2385/5130), and 26.5% (1901/7174) of patients in T1, T2, and T3, respectively (P<0.001 for trend). The nonavalent vaccine could have protected against HPV in 92.5% (1259/1361), 72.3% (3709/5130), and 58.1% (4168/7174) of patients in T1, T2, and T3, respectively (P<0.001 for trend). The proportion of patients with genital dysplasia grade 2+ who did not have infections with HPV genotypes covered by the quadrivalent or nonavalent vaccines increased across the three periods (P<0.001 for trend). For all study periods, the protection provided by the nonavalent vaccine would have been superior to the quadrivalent vaccine (χ2 test P<0.001). CONCLUSION: The introduction of a nonavalent vaccine could improve protection against HPV infections and HPV-related genital dysplasia.

Oncologic effectiveness of nerve-sparing radical hysterectomy in cervical cancer.

OBJECTIVE: Nerve-sparing radical hysterectomy (NSRH) was introduced with the aim to reduce pelvic dysfunctions related to conventional radical hysterectomy (RH). Here, we sought to assess the effectiveness and safety of NSRH in a relatively large number of the patients of cervical cancer (CC) patients undergoing either primary surgery or neoadjuvant chemotherapy (NACT) followed by surgery. METHODS: Outcomes of consecutive patients undergoing NSRH and of a historical cohort of patients undergoing conventional RH were retrospectively reviewed. RESULTS: This study included 325 (49.8%) and 327 (50.2%) undergoing NSRH and RH, respectively. Via a multivariable model, nodal status was the only factor predicting for DFS (hazard ratio [HR]=2.09; 95% confidence interval [CI]=1.17-3.73; p=0.01). A trend towards high risk of recurrence was observed for patients affected by locally advanced cervical cancer (LACC) undergoing NACT followed by surgery (HR=2.57; 95% CI=0.95-6.96; p=0.06). Type of surgical procedures (NSRH vs. RH) did not influence risk of recurrence (p=0.47). Similarly, we observed that the execution of NSRH rather than RH had not a detrimental effect on OS (HR=1.19; 95% CI=0.16-9.01; p=0.87). Via multivariable model, no factor directly correlated with OS. No difference in early complication rates was observed between the study groups. Conversely, a significant higher number of late complications was reported in RH versus NSRH groups (p=0.02). CONCLUSION: Our data suggested that NSRH upholds effectiveness of conventional RH, without increasing recurrence and complication rates but improving pelvic dysfunction rates.

Invasive Paget Disease of the Vulva.

OBJECTIVE: Extramammary Paget disease of the vulva (EPDV) is a rare occurrence with an indolent and relapsing course. Progression to invasion occurs in 4% to 19% of cases. The aim of this study is to report clinical-pathological features and outcomes of patients treated for invasive EPDV. METHODS: Data of consecutive patients treated between 2000 and 2017 for invasive EPDV were reviewed. RESULTS: Among 79 patients with EPDV, 10 (12.7%) presented a microinvasive or invasive form at first diagnosis or during follow-up. All of them underwent upfront radical surgery; 7 (70%) received subsequent radiotherapy, chemotherapy, or both. The mortality rate was 40%. The recurrence rate after treatment for invasive forms was 60%, with a mean time to first recurrence of 20 (range, 5-36) months. CONCLUSIONS: Our study confirms that invasive EPDV remains a rare gynecological neoplasm with a poor prognosis. Multicentre trials or well-organized prospective data collection could improve the knowledge about the management of invasive EPDV.

The Impact of Number of Cycles of Neoadjuvant Chemotherapy on Survival of Patients Undergoing Interval Debulking Surgery for Stage IIIC-IV Unresectable Ovarian Cancer: Results From a Multi-Institutional Study.

OBJECTIVES: Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) may be a valuable treatment option in advanced ovarian cancer when primary cytoreduction is not feasible. However, a consensus on the ideal number of NACT cycles is still lacking. In the present investigation, we aimed to evaluate how number of cycles of NACT influenced patients' outcomes. METHODS: Data of consecutive patients undergoing NACT and IDS were retrospectively reviewed in 4 Italian centers, and survival outcomes were evaluated. RESULTS: Overall, 193 patients were included. Cycles of NACT were 3, 4, and at least 5 in 77 (40%), 74 (38%), and 43 (22%) patients, respectively. Patients undergoing 3 cycles experienced a similar disease-free survival (hazard ratio [HR], 1.12; 95% confidence interval [CI], 0.89-1.65; P = 0.20) but an improved overall survival (HR, 1.64; 95% CI, 1.05-2.4; P = 0.02) in comparison to patients receiving at least 4 cycles. Five-year overall survival was 46% and 31% for patients having 3 and at least 4 cycles. Ten-year overall survival was 26% and 18% for patients having 3 and at least 4 cycles (HR, 1.70; 95% CI, 1.13-2.55; P = 0.009). Using multivariate analysis, we observed that only Eastern Cooperative Oncology Group performance status correlated with overall survival (HR, 1.76; 95% CI, 1.2-2.49; P = 0.001). In addition, a trend toward worse overall survival was observed for patients with residual disease at IDS (HR, 1.29; 95% CI, 0.98-1.70; P = 0.06) and patients receiving at least 4 cycles (HR, 1.76; 95% CI, 0.95-3.22; P = 0.06). CONCLUSION: Our data underline the potential implication of number of cycles of NACT before IDS. Further prospective studies are warranted to assess this correlation.

Ovarian Cancer in Elderly Patients: Patterns of Care and Treatment Outcomes According to Age and Modified Frailty Index.

OBJECTIVE: The present study assessed the predictive value of age and Modified Frailty Index (mFI) on the management of primary epithelial ovarian cancer (EOC) patients aged 70 years or older (elderly). METHODS: A retrospective multicenter study selected elderly EOC patients treated between 2006 and 2014. Treatments were analyzed according to the following age group categories: (1) 70 to 75 years versus (2) older than 75 years, and mFI of less than 4 (low frailty) versus greater than or equal to 4 (high frailty). RESULTS: Seventy-eight patients were identified (40 in age group 1 and 38 in age group 2). The mFI was greater than or equal to 4 in 23 women. Median age of low frailty and high frailty was not significantly different (75.6 vs 75.3). Comorbidities were equally distributed according to age, whereas diabetes, hypertension, obesity, and chronic renal failure were more frequent in the high-frailty group. Performance status was different only according to mFI. Twenty percent of age group 1 versus 55.3% of age group 2 underwent none or only explorative surgical approach (P = 0.003), whereas surgical approaches were similar in the 2 frailty groups. The rate of postoperative complications was higher in high-frailty patients compared with low-frailty patients (23.5% vs 4.3%; P = 0.03). Chemotherapy was administered to all the patients, a monotherapy regimen to 50% of them. No differences in toxicity were registered, except more hospital recovery in the high-frailty cohort. Median survival time was in favor of younger patients (98 versus 30 months) and less-frailty patients (56 vs 27 months). CONCLUSIONS: Elderly EOC patients can receive an adequate treatment, but patients who are older than 75 years can be undertreated, if not adequately selected. The pretreatment assessment of frailty through mFI could be suggested in the surgical and medical management.

Sentinel node mapping in endometrial cancer following Hysteroscopic injection of tracers: A single center evaluation over 200 cases.

OBJECTIVES: To analyze detection-rate(DR) and diagnostic-accuracy (A) of sentinel-nodes(SLNs) mapping following hysteroscopic-injection of tracer. To compare DR and A between tracers: ICG and Tc99m. METHODS: Evaluation of endometrial-cancer patients who underwent SLNs mapping after hysteroscopic-peritumoral-injection of tracer±lymphadenectomy. Analysis of DR (overall-bilateral-aortic) and A in the entire cohort and comparison between tracers. RESULTS: 202 procedures were performed from January/2005 to February/2017. Mean age:60years (28-82); mean BMI: 26.8 kg/m2 (15-47). In 133 cases (65.8%) hysterectomy and mapping procedure were performed laparoscopically. The overall-DR of the technique was 93.2% (179/192) (10 cases were excluded: 9 for technical-equipment failure; 1 for vagal reaction). Bilateral pelvic mapping was found in 59.7% of cases (107/179) and was more frequent in the ICG group (72.8% vs 53.3%; p: 0.012). In 50.8% of cases (91/179) SLNs were mapped both in pelvic and aortic nodes, and in 5 cases (2.8%) only in the aortic area. The mean number of detected SLNs was 3.7 (1-8). 22 patients (12.3%) had nodal involvement: 10-(45.5%)-macrometastases; 5-(22.7%)-micrometastases; 7-(31.8%)-ITCs. In 6 cases (27.3%) only aortic nodes were positive; in 5 cases (22.7%) both pelvic and aortic nodes and in 11 cases (50%) only pelvic nodes were involved. Three false-negative results were found, all in the Tc99m group. All had isolated aortic metastases with negative pelvic nodes. Overall-sensitivity was 86.4% (95%CI: 68.4-100) and overall-negative-predictive-value (NPV) was 96.4% (95%CI 86.7-100). No differences in terms of overall-DR, overall-sensitivity and overall-NPV were found between the two tracers. CONCLUSIONS: Hysteroscopic-injection of tracer for SLNs mapping in endometrial cancer is as accurate as cervical injection with a higher DR in the aortic area. ICG improves bilateral-DR. Further investigation is warranted on this topic.

Impact of Surgical Route in Influencing the Risk of Lymphatic Complications After Ovarian Cancer Staging.

Lymphatic complications are a common occurrence after staging surgery for early-stage ovarian cancer (eEOC). We investigated whether the introduction of minimally invasive surgery influences the risk of developing lymphoceles and lymphorrhea in patients undergoing staging for eEOC. For this purpose, data of consecutive patients affected by eEOC undergoing staging surgery between January 1980 and January 2016 were retrospectively reviewed, and a systematic review and meta-analysis was performed. This systematic review was registered in the International Prospective Register of Systematic Review. Among 341 patients included in the present study, 47 severe postoperative complications occurred (13.7%), including 40 lymphatic complications: 31 symptomatic lymphoceles (9%) and 9 cases of lymphorrhea (2.6%), respectively. Laparoscopic staging correlated with a lower risk of developing any severe lymphatic complications in comparison with open surgery (p = .02). In particular, the laparoscopic approach and para-aortic node involvement were associated with a trend toward lower lymphoceles (odds ratio, .13; 95% confidence interval, .07-2.20; p = .05) and a trend toward higher risk of lymphorrhea developing (odds ratio, 4.02; 95% confidence interval, .93-17.3; p = .06), respectively. In conclusion, the implementation of a minimally invasive approach might result in a slight reduction of lymphatic complications after eEOC staging.

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.

Ovarian cancer treatment in mutation carriers/BRCAness.

Epithelial ovarian cancer remains the most lethal gynecologic malignancy. During the last 15 years, there has been only marginal improvement in 5-year overall survival. These daunting statistics are compounded by the fact that despite all subtypes exhibiting striking heterogeneity, their systemic management remains identical. Retrospective studies have shown an improved prognosis, higher response rates to platinum-containing regimens, and longer treatment-free intervals between relapses in patients with BRCA 1 and BRCA 2 (BRCA1/2)-mutated ovarian cancer (BMOC) compared with patients who are not carriers of this mutation. These features of BMOC are attributed to homologous-recombination repair deficiency in the absence of BRCA1/2 function, which results in an impaired ability of tumor cells to repair platinum-induced double-strand breaks, thereby conferring increased chemosensitivity and increased sensitivity to poly(ADP-ribose) polymerase enzyme inhibition and other DNA-damaging chemotherapeutic agents such as pegylated liposomal doxorubicin (PLD). Therefore, the chemotherapeutic approach for patients with BMOC should focus on treatment with platinum-based chemotherapy at first-line and recurrent-disease settings and measures to increase the platinum-free interval following early platinum-resistant relapse by using non-platinum cytotoxic agents, with the aim of reintroducing platinum again at a later date. The role of first-line intraperitoneal platinum-based therapy in the specific context of BMOC also merits further analysis. Other than platinum, alternative DNA-damaging agents (including PLD and trabectedin) also may have a therapeutic role in patients with recurrent BMOC. The approval of olaparib for clinical use in Europe and the United States will also affect chemotherapeutic strategies for these patients. Further work to clarify the precise relationship between BRCA1/2 mutation genotype and clinical phenotype is crucial to delineating the optimal therapeutic choices in the future for patients with BMOC.

A critical assessment on the role of sentinel node mapping in endometrial cancer.

Endometrial cancer is the most common gynecologic malignancy in the developed countries. Although the high incidence of this occurrence no consensus, about the role of retroperitoneal staging, still exists. Growing evidence support the safety and efficacy of sentinel lymph node mapping. This technique is emerging as a new standard for endometrial cancer staging procedures. In the present paper, we discuss the role of sentinel lymph node mapping in endometrial cancer, highlighting the most controversies features.

Complications after the treatment of endometrial cancer: a prospective study using the French-Italian glossary.

INTRODUCTION: The evaluation of treatment complications is crucial in modern oncology because they heavily influence the every day life of patients. Several authors confirmed the reproducibility of the French-Italian glossary to score the complications in patients with endometrial cancer after radiotherapy (RT), but the treatment of endometrial carcinoma is primarily surgical and chemotherapy is often used for high-risk disease. OBJECTIVES: This study aimed to analyze the incidence of complications in our patients treated for endometrial cancer and to verify whether the glossary is a suitable instrument in the description of complications after surgery, RT, and chemotherapy. METHODS: The data of patients affected by endometrial cancer treated in the Gynecology and Obstetrics Academic Department, Azienda Ospedaliera Mauriziano Umberto I in Turin from 2000 to 2009 (with surgery alone or integrated treatments) were prospectively collected, and complications were described using the glossary. Every patient included in the analyses had a minimum of 18 months follow-up. RESULTS: Of the 271 patients, 68 (25%) experienced at least 1 complication with 87 overall complications. Most of the complications were mild (63%) and were found in the urinary (30%) or cutaneous systems (30%). Forty-four (50%) complications appeared within 1 year after treatment, but 9 (10%) complications appeared after 60 months of follow-up. Patients who were submitted to both surgery and RT showed a trend of higher rate of at least 1 complication (19/58 [32.7%]) if compared with surgery alone (36/135 [26.6%]), even if the difference was not statistically significant (P = 0.09). The incidence of complications in patients treated or not with lymphadenectomy was not statistically different (P = 0.088), whereas patients treated with laparotomy had a higher rate of cutaneous complications if compared with the laparoscopic approach (P = 0.018). The glossary included all observed complications. CONCLUSIONS: One every 4 women treated for endometrial cancer develops a complication. Clinicians should check for complications especially after integrated treatments maintaining surveillance even in the long term. The glossary is a comprehensive instrument to describe the complications of endometrial cancer, regardless of the type of treatment delivered.

Aggressive clinical course of primary invasive vaginal carcinoma associated with type 61 HPV: a case report.

Primary invasive vaginal cancer is one of the rarest malignant processes in the female genital tract. The etiology has not been identified, but the strongest association is with HPV infection and subtypes 16 and 18 have the highest oncogenic potential. We present the case of a young woman diagnosed with metastatic squamous cell carcinoma of the vagina associated with HPV type 61, a non-oncogenic HPV type. We report the propensity of a primary vaginal neoplasm to spread to lymphatic vessels early and the unresponsive aggressive behavior to multimodal therapy.

Variation in gynecological oncology follow-up practice: attributable to cancer centers or to patient characteristics? A Piedmont Regional Oncology Network Study.

AIMS AND BACKGROUND: Although guidelines recommend minimalist follow-up, there is wide variability in gynecological oncology practice. The aims of this study were to describe between-center differences in the follow-up of endometrial, ovarian, and uterine cervical cancer; to identify the determinants of test prescription; to estimate the related costs; and to assess the weight of center habits and patient characteristics as sources of unexplained variability. METHODS AND STUDY DESIGN: The medical records of patients treated between August 2004 and July 2005 for gynecological malignancies and followed up for the detection of recurrent disease were retrospectively collected from 29 centers of the Piedmont Oncology Network. Multivariate multilevel analyses were performed to study the determinants of test prescription and costs. RESULTS: Analyses were performed on 351 patients (median follow-up: 578 days). The unexplained variability in computed tomography prescriptions (26%), ultrasound prescriptions (17%), and total cost of follow-up (15%) can be attributed to center habits, independenty of the clinical characteristics of the patients. CONCLUSIONS: Much of the unexplained variability in the follow-up for gynecological malignancies is attributable to different habits of centers belonging to a cancer network. These results prompted us to design a multicenter randomized controlled trial to compare minimalist versus intensive follow-up programs in endometrial cancer.

Gemcitabine and vinorelbine combination in platinum-sensitive recurrent ovarian cancer.

OBJECTIVES: Most patients with ovarian cancer are candidates for second-line or salvage treatments often for prolonged periods. Patients with platinum-sensitive disease can benefit from a platinum retreatment with a likelihood of response dependents on the treatment-free interval. Alternative agents and combination chemotherapy are potential therapeutic approaches. At our institution, we carried out a phase II trial to evaluate feasibility, efficacy, and toxicity of gemcitabine and vinorelbine combination in recurrent ovarian carcinoma. The aim of the present study was to evaluate the role of this combination in patients with platinum-sensitive disease. PATIENTS AND METHODS: Patients with platinum-sensitive disease recurring after 1 or more lines of platinum-based chemotherapy were included. Vinorelbine at 25 mg/m followed by gemcitabine at 1000 mg/m was administered intravenously on days 1 and 8 every 3 weeks. Response Evaluation Criteria in Solid Tumors and cancer antigen 125 test (CA-125 Kinetics [Rustin criteria]) were adopted to classify responses. Toxicity was assessed according to the National Cancer Institute Common Toxicity Criteria. RESULTS: Thirty-nine patients were eligible. Platinum-free interval (PFI) was 6 to 12 months in 13 patients (33.3%; PFI 6-12) and more than 12 months in 26 patients (66.7%; PFI > 12). The overall response rate was 48.7%, with 6 complete responses. Median response duration was 38 weeks. The response rate was 23% in PFI 6-12 and 62% in PFI >12. The most frequently observed toxicity was hematological, with 23% of the patients having grade 3 or 4 neutropenia. CONCLUSIONS: Gemcitabine and vinorelbine combination is effective and well tolerated in recurrent platinum-sensitive ovarian cancer. It may represent an option in the management of these patients because the chronic nature of the disease.