Outcomes of High-Grade Cervical Dysplasia with Positive Margins and HPV Persistence after Cervical Conization.

The objective of this work is to assess the 5-year outcomes of patients undergoing conization for high-grade cervical lesions that simultaneously present as risk factors in the persistence of HPV infection and the positivity of surgical resection margins. This is a retrospective study evaluating patients undergoing conization for high-grade cervical lesions. All patients included had both positive surgical margins and experienced HPV persistence at 6 months. Associations were evaluated with Cox proportional hazard regression and summarized using hazard ratio (HR). The charts of 2966 patients undergoing conization were reviewed. Among the whole population, 163 (5.5%) patients met the inclusion criteria, being at high risk due to the presence of positive surgical margins and experiencing HPV persistence. Of 163 patients included, 17 (10.4%) patients developed a CIN2+ recurrence during the 5-year follow-up. Via univariate analyses, diagnosis of CIN3 instead of CIN2 (HR: 4.88 (95%CI: 1.10, 12.41); p = 0.035) and positive endocervical instead of ectocervical margins (HR: 6.44 (95%CI: 2.80, 9.65); p < 0.001) were associated with increased risk of persistence/recurrence. Via multivariate analyses, only positive endocervical instead of ectocervical margins (HR: 4.56 (95%CI: 1.23, 7.95); p = 0.021) were associated with worse outcomes. In this high-risk group, positive endocervical margins is the main risk factor predicting 5-year recurrence.

Development of a Nomogram Predicting the Risk of Persistence/Recurrence of Cervical Dysplasia.

Background: Cervical dysplasia persistence/recurrence has a great impact on women's health and quality of life. In this study, we investigated whether a prognostic nomogram may improve risk assessment after primary conization. Methods: This is a retrospective multi-institutional study based on charts of consecutive patients undergoing conization between 1 January 2010 and 31 December 2014. A nomogram assessing the importance of different variables was built. A cohort of patients treated between 1 January 2015 and 30 June 2016 was used to validate the nomogram. Results: A total of 2966 patients undergoing primary conization were analyzed. The median (range) patient age was 40 (18-89) years. At 5-year of follow-up, 6% of patients (175/2966) had developed a persistent/recurrent cervical dysplasia. Median (range) recurrence-free survival was 18 (5-52) months. Diagnosis of CIN3, presence of HR-HPV types, positive endocervical margins, HPV persistence, and the omission of HPV vaccination after conization increased significantly and independently of the risk of developing cervical dysplasia persistence/recurrence. A nomogram weighting the impact of all variables was built with a C-Index of 0.809. A dataset of 549 patients was used to validate the nomogram, with a C-index of 0.809. Conclusions: The present nomogram represents a useful tool for counseling women about their risk of persistence/recurrence after primary conization. HPV vaccination after conization is associated with a reduced risk of CIN2+.

High-risk HPV-positive and -negative high-grade cervical dysplasia: Analysis of 5-year outcomes.

OBJECTIVE: To evaluate the outcomes of high-risk (HR) HPV-positive and -negative women affected by high-grade cervical dysplasia. METHODS: This is a retrospective multi-institutional study. Medical records of consecutive patients with high-grade cervical dysplasia undergoing conization between 2010 and 2014 were retrieved. All patients included had at least 5 years of follow-up. A propensity-score matching was adopted in order to reduce the presence of confounding factors between groups. Kaplan-Meir and Cox hazard models were used to estimate 5-year outcomes. RESULTS: Overall, data of 2966 women, affected by high-grade cervical dysplasia were reviewed. The study population included 1478 (85%) and 260 (15%) women affected by HR-HPV-positive and HR-HPV-negative high-grade cervical dysplasia. The prevalence of CIN2 and CIN3 among the HR-HPV-positive and -negative cohort was similar (p = 0.315). Patients with HR-HPV-positive high-grade cervical dysplasia were at higher risk of 5-year recurrence (after primary conization) that HR-HPV-negative patients (p < 0.001, log-rank test). Via multivariate analysis, HR-HPV-negative women were at low risk of recurrence (HR: 1.69 (95%CI: 1.05, 4.80); p = 0.018, Cox Hazard model). A propensity-score matched comparison was carried out in order to reduce biases that are related to the retrospective study design. In comparison to HR-HPV-negative patients, thosewith HR-HPV-positive CIN3 was associate with a 8-fold increase in the risk of recurrence (p < 0.001, log-rank test). CONCLUSIONS: HR-HPV-negative high-grade cervical dysplasia is not uncommon, accounting for 15% of our study population. Those patients experience more favorable outcomes than patients with documented HR-HPV infection(s). Further prospective studies are needed to corroborate our data.

Assessing the Long-Term Role of Vaccination against HPV after Loop Electrosurgical Excision Procedure (LEEP): A Propensity-Score Matched Comparison.

Background: Primary prevention through vaccination is a prophylactic approach aiming to reduce the risk of developing human papillomavirus (HPV)-related lesions. No mature and long-term data supported the adoption of vaccination in women undergoing conization. Methods: This is a retrospective multi-institutional study. Charts of consecutive patients undergoing conization between 2010 and 2014 were collected. All patients included had at least 5 years of follow-up. We compared outcomes of patients undergoing conization plus vaccination and conization alone. A propensity-score matching algorithm was applied in order to reduce allocation biases. The risk of developing recurrence was estimated using Kaplan-Meir and Cox hazard models. Results: Overall, charts of 1914 women were analyzed. The study group included 116 (6.1%) and 1798 (93.9%) women undergoing conization plus vaccination and conization alone, respectively. Five-year recurrence rate was 1.7% (n = 2) and 5.7% (n = 102) after conization plus vaccination and conization alone, respectively (p = 0.068). After the application of a propensity-score matching, we selected 100 patients undergoing conization plus vaccination and 200 patients undergoing conization alone. The crude number of recurrences was 2 (2%) and 11 (5.5%) for patients undergoing conization plus vaccination and conization alone, respectively (p = 0.231). Vaccination had no impact on persistent lesions (no negative examination between conization and new cervical dysplasia; p = 0.603), but reduced the risk of recurrent disease (patients who had at least one negative examination between conization and the diagnosis of recurrent cervical dysplasia; p = 0.031). Conclusions: Patients having vaccination experience a slightly lower risk of recurrence than women who had not, although not statistically significantly different. Further evidence is needed to assess the cost effectiveness of adopting vaccination in this setting.

Recurrence rate after loop electrosurgical excision procedure (LEEP) and laser Conization: A 5-year follow-up study.

OBJECTIVE: Conization aims to remove pre-neoplastic lesions of the uterine cervix. Several techniques for conization have been compared, but evidence regarding the most effective therapeutic option is scant. Here, we aimed to compare the recurrence rate following laser conization and loop electrosurgical excision procedure (LEEP) in patients with high-grade cervical dysplasia (HSIL/CIN2+). METHODS: This is a retrospective multi-institutional study. Medical records of consecutive patients with HSIL/CIN2+ undergoing conization between 2010 and 2014 were retrieved. A propensity-score matching (PSM) was applied in order to reduce allocation bias. The risk of developing recurrence was estimated using Kaplan-Meir and Cox hazard models. RESULTS: Overall, 2966 patients had conization over the study period, including 567 (20%) and 2399 (80%) patients having laser conization and LEEP, respectively. Looking at predictors of recurrence, diagnosis of CIN3 (HR:3.80 (95%CI:2.01,7.21); p < 0.001) and HPV persistence (HR:1.81 (95%CI:1.11,2.96); p < 0.001) correlated with an increased risk of recurrence. After applying a PSM we selected 500 patients undergoing laser conization and 1000 undergoing LEEP. Patients undergoing LEEP were at higher risk of having positive surgical margins in comparison to patients undergoing laser conization (11.2% vs. 4.2%). The risk of having persistence of HPV was similar between the two groups (15.0% vs. 11.6%;p = 0.256). Five-year recurrence rate was 8.1% and 4% after LEEP and laser conization, respectively (p = 0.023). HPV persistence was the only factor associated with [5-]year recurrence after both laser conization (p = 0.003) and LEEP (p = 0.001). CONCLUSIONS: HPV persistence is the only factor associated with an increased risk of recurrence after either laser conization or LEEP. Owing to the lack of data regarding obstetrical outcomes, we are not able to assess the best therapeutic option for women with cervical dysplasia.

Surgical Techniques for Diaphragmatic Resection During Cytoreduction in Advanced or Recurrent Ovarian Carcinoma: A Systematic Review and Meta-analysis.

OBJECTIVE: Optimal cytoreduction is one the main factors improving survival outcomes in patients affected by ovarian cancer (OC). It is estimated that approximately 40% of OC patients have gross disease located on the diaphragm. However, no mature data evaluating outcomes of surgical techniques for the management of diaphragmatic carcinosis exist. In the present study, we aimed to estimate surgery-related morbidity of different surgical techniques for diaphragmatic cytoreduction in advanced or recurrent OC. METHODS: PubMed (MEDLINE), Web of Science, and Clincaltrials.gov databases were searched for records estimating outcomes of diaphragmatic peritoneal stripping (DPS) or diaphragmatic full-thickness resection (DFTR) for OC. The meta-analysis was performed using the Cochrane Review software. RESULTS: For the final analysis, 5 articles were available, including 272 patients. Diaphragmatic peritoneal stripping and DFTR were performed in 197 patients (72%) and 75 patients (28%), respectively. Pooled analysis suggested that the estimated pleural effusion rate was 43% and 51% after DPS and DFTR, respectively. The need for pleural punctures or chest tube placement was 4% and 9% after DPS and DFTR, respectively. The rate of postoperative pneumothorax (4% vs 9%; odds ratio, 0.31; 95% confidence interval, 0.05-2.08) and subdiaphragmatic abscess (3% vs 3%; odds ratio, 0.45; 95% confidence interval, 0.09-2.31) were similar after the execution of DPS and DFTR. CONCLUSIONS: Diaphragmatic surgery is a crucial step during cytoreduction for advanced or recurrent OC. Obviously, the choice to perform DPS or DFTR depends on the infiltration of the diaphragmatic muscle or not. Both the procedures are associated with a low pulmonary complication and chest tube placement rates.

FDG-PET/CT to predict optimal primary cytoreductive surgery in patients with advanced ovarian cancer: preliminary results.

AIMS AND BACKGROUND: Primary cytoreductive surgery (CRS) has a significant impact on prognosis in epithelial ovarian cancer (EOC). Patient selection is important to recognize factors limiting optimal CRS and to avoid unnecessary aggressive surgical procedures. We evaluated the contribution of fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in the presurgical identification of disease sites that may preclude EOC cytoreducibility. METHODS: Patients with suspected EOC underwent 18F-FDG-PET/CT within 20 days before debulking surgery. The PET/CT results were compared with surgical findings and postsurgery histopathology in order to assess the diagnostic value. RESULTS: Between August 2013 and January 2014, 29 patients were evaluated. The histopathology showed 23 EOC and 6 benign tumors. The FDG-PET/CT was positive (maximum standardized uptake value [SUVmax] 11.3 ± 5.4) in 21/23 (91%) patients with EOC and provided 2 false-negatives (1 mucinous and 1 clear cell carcinoma; SUVmax ≤2.8). The FDG-PET/CT was true-negative (SUVmax 2.2 ± 1.6) in 4 out of 6 patients (67%). False-positive FDG-PET results were obtained in 2 cellular fibromas (SUVmax 4.8 and 5.6). The sensitivity, specificity, and accuracy of PET/CT to characterize ovarian masses were 91%, 67%, and 86%, respectively. Among the 21 FDG-PET/CT-positive EOC, we detected factors limiting optimal CRS in 6 cases (29%): 4 hepatic hilum infiltration and 2 root mesentery involvement, confirmed at surgical exploration. The FDG-PET did not find limiting factors in the remaining 15 patients (71%) in whom optimal CRS was obtained. CONCLUSIONS: Fluorodeoxyglucose-PET/CT shows high sensitivity but suboptimal specificity in the characterization of ovarian masses. However, PET/CT may play a role in noninvasively selecting patients with EOC who can benefit from primary CRS.

Morcellation of undiagnosed uterine sarcoma: A critical review.

In the recent decades, laparoscopy has replaced open abdominal procedures in the setting of gynecologic surgery. Extraction of large specimens (e.g., large uteri or myomas) following operative laparoscopy is technically challenging. Technological attempts allow the removal of large and solid pelvic masses via small abdominal incisions (using instruments called morcellators), thus reducing unnecessary laparotomies and improving short-term patients' outcomes. However, morcellation of undiagnosed uterine malignancies may lead to worse survival outcomes. Therefore, the Food and Drug Administration (FDA) warns about the use of power morcellators, thus causing ongoing concerns on the applicability of minimally invasive approaches for myomectomy and the removal of large uteri. In the present review, we sought to assess pro and cons regarding minimally invasive morcellation. This review will discuss the effects of morcellation of undiagnosed uterine malignancies, focusing on possible techniques for preoperative detection of uterine sarcoma and for avoiding intra-abdominal dissemination of potentially malignant tissues. Further efforts are necessary in order to identify tools to make a more accurate and reliable preoperative diagnosis of uterine masses. However, on the light of the current evidence, intra-abdominal morcellation should be banned from clinical practice.

When Does Neoadjuvant Chemotherapy Really Avoid Radiotherapy? Clinical Predictors of Adjuvant Radiotherapy in Cervical Cancer.

BACKGROUND: The aim of this study was to identify clinical variables that may predict the need for adjuvant radiotherapy after neoadjuvant chemotherapy (NACT) and radical surgery in locally advanced cervical cancer patients. METHODS: A retrospective series of cervical cancer patients with International Federation of Gynecology and Obstetrics (FIGO) stages IB2-IIB treated with NACT followed by radical surgery was analyzed. Clinical predictors of persistence of intermediate- and/or high-risk factors at final pathological analysis were investigated. Statistical analysis was performed using univariate and multivariate analysis and using a model based on artificial intelligence known as artificial neuronal network (ANN) analysis. RESULTS: Overall, 101 patients were available for the analyses. Fifty-two (51 %) patients were considered at high risk secondary to parametrial, resection margin and/or lymph node involvement. When disease was confined to the cervix, four (4 %) patients were considered at intermediate risk. At univariate analysis, FIGO grade 3, stage IIB disease at diagnosis and the presence of enlarged nodes before NACT predicted the presence of intermediate- and/or high-risk factors at final pathological analysis. At multivariate analysis, only FIGO grade 3 and tumor diameter maintained statistical significance. The specificity of ANN models in evaluating predictive variables was slightly superior to conventional multivariable models. CONCLUSIONS: FIGO grade, stage, tumor diameter, and histology are associated with persistence of pathological intermediate- and/or high-risk factors after NACT and radical surgery. This information is useful in counseling patients at the time of treatment planning with regard to the probability of being subjected to pelvic radiotherapy after completion of the initially planned treatment.

Long-term safety of fertility sparing surgery in early stage ovarian cancer: comparison to standard radical surgical procedures.

OBJECTIVE: Fertility-sparing surgery (FSS) is a strategy often considered in young patients with low-grade (G1-2) early-stage epithelial ovarian cancer (eEOC), while is still controversial in high-risk patients. We investigated the role of FSS in low and high-risk eEOC patients undergoing comprehensive surgical staging. METHODS: We analyzed data from patients operated for an eEOC from 1975 to 2011, focusing on patients submitted to FSS. Seventy patients out of 307 with eEOC were identified. Patients underwent FSS were compared with 237 patients underwent radical-comprehensive-staging (RCS) in the same period. Disease free (DFS) and overall (OS) survivals were evaluated using Kaplan-Meier and Cox models. RESULTS: Overall, 307 patients had surgery for eEOC: 70 (22.8%) and 237 (77.2%) women had FSS and RCS, respectively. At univariate analysis, the execution of FSS not influenced DFS (HR:1.06 (95%CI: 0.56,2.02); p=0.84) and OS (HR:1.94 (95%CI: 0.75,4.98); p=0.16). Stage of disease was the only factor correlating with DFS (HR:4.73; 95%CI: 2.01,11.11; p<0.001). Independently, increased age (HR per 1-unit of age:1.06 (95%CI: 1.03,1.11); p<0.001) and high risk disease (HR:3.26; 95%CI: 1.23,8.62; p=0.01) remained associated with worse OS. Focusing on the high risk group (stage IAG3 or more) we observed that type of surgery (FSS v. RCS) did not influence DFS (p=0.77, log-rank test) and OS (p=0.08, log-rank test). CONCLUSIONS: FSS upholds oncologic effectiveness of RCS, preserving reproductive and endocrine functions. FSS does not increase risk of recurrence among high risk eEOC patients. Further prospective studies on this issue are warranted to improve patients' care.

Surgical treatment of an isolated omental cervical cancer recurrence: report of a case and review of the literature.

AIMS AND BACKGROUND: Recurrent cervical cancer has traditionally been associated with a dismal prognosis. Historically, patients who developed distant metastases from cervical cancer were not considered eligible for surgical resection; only palliative treatment options are available, generally consisting of chemo- and/or radiotherapy. Metastases usually appear in the liver, lung or lymph nodes. The abdominal cavity is a quite unusual site of recurrence and the disease usually has multiple foci. For this reason, peritoneal involvement by cervical cancer is considered a contraindication to local treatment. METHODS AND STUDY DESIGN: We report the first case of a 30-year-old woman with isolated intra-abdominal cervical cancer recurrence diagnosed with 18F-FDG PET/CT, successfully surgically treated. RESULTS: Histopathological analysis confirmed the tumor to be an omental relapse of squamous cervical cancer previously treated with anterior pelvic exenteration and platinum based chemotherapy. The patient underwent adjuvant treatment with 3 cycles of topotecan and has remained free of disease during the 4 years of follow-up. CONCLUSIONS: In selected cases with isolated recurrences, a surgical resection may provide a long term complete remission in recurrent cervical cancer patients.

Intraperitoneal chemotherapy by ultrasound-guided direct puncture in recurrent ovarian cancer: feasibility, compliance, and complications.

OBJECTIVE: This prospective pilot study investigated the feasibility, complications, and compliance of the administration of intraperitoneal (IP) chemotherapy by direct puncture under ultrasonographic guidance performed on consecutive patients with recurrent ovarian cancer (ROC). METHODS: Patients were evaluated to undergo secondary cytoreduction and/or to receive IP chemotherapy. Patients received standard intravenous therapy for ROC plus IP administration by direct puncture needle, under ultrasonographic guidance. RESULTS: From January 2008 to January 2011, 38 patients were enrolled. A total of 402 IP procedures were performed, with a mean of 10.5 procedures per patient. The feasibility rate was 97.4%. In 237 cases (98.8%) of subgroup 1 (abdominal wall thickness ≤6 cm), the procedure was performed after 1 attempt, meanwhile in 6% of cases of subgroup 2 (abdominal wall thickness >6 cm), more than 1 attempt was necessary (P < 0.01). The mean procedure time was 10 minutes (range, 5-30 minutes). We recorded a total of 2.25% mild intraprocedure complications. No significant difference was identified for the complication rate according to the abdominal wall thickness or according to the number of previous laparotomies. A total of 5 procedures (1.2%) were not performed as a result of patients' noncompliance. The mean pain score according to the visual analog pain scale was moderate at the first evaluation (after 3 minutes) and mild at the final evaluation (after 10 minutes). CONCLUSIONS: The administration of IP chemotherapy with a direct puncture, under ultrasound guidance, for patients with ROC, is a safe and feasible method, with a high acceptance from patients.