Is Cardiopulmonary Exercise Testing Predictive of Surgical Complications in Patients Undergoing Surgery for Ovarian Cancer?

Preoperative cardiopulmonary exercise testing (CPET) provides an objective assessment of functional capability. In other intra-abdominal surgical specialties, CPET outcomes are predictive of operative morbidity. However, in ovarian cancer surgery, its predictive value remains unknown. In this study, we evaluated the association between CPET performance and surgical morbidity in ovarian cancer patients. Secondly, we assessed the association between CPET performance and other surgical outcomes (i.e., hospital stay, readmission and residual disease). This was a retrospective cohort study of patients undergoing primary surgery for ovarian cancer between 2020 and 2023. CPET performance included peak oxygen uptake (VO2 max), ventilatory efficiency (VE/VO2) and anaerobic threshold. Outcomes were operative morbidity and included intra- and postoperative complications (Clavien-Dindo), hospital stay, readmission within 30 days and residual disease. A total of 142 patients were included. A lower VO2 peak and a higher VE/VCO2 were both associated with the occurrence of postoperative complications, and a poorer anaerobic threshold was associated with more transfusions. VE/VCO2 remained significantly associated after multivariate analysis (p = 0.035). None of the CPET outcomes were associated with length of stay, readmission or residual disease. In conclusion, VE/VCO2 was significantly associated with an increased risk of all-cause postoperative complications in ovarian cancer patients undergoing primary surgery.

Conservative surgical approaches for small volume FIGO stage IB1 cervical cancer. Updated survival and obstetric outcomes of an expanded cohort.

OBJECTIVE: Standard surgical treatment of FIGO stage 1B1 cervical cancer is open radical surgery. However, there is increasing evidence that for small tumours a more conservative approach can minimise fertility consequences without impacting on long term oncologic outcomes. The objective of our study is to present survival and obstetric outcomes following extended follow-up for patients who underwent conservative management of small-volume stage 1B1 disease. METHODS: All patients with FIGO stage 1B1 cancer and estimated tumour volume of <500 mm3 in a loop biopsy specimen treated in Northern Gynaecological Oncology Centre between December 2000 and December 2021, were included in the study. Clinico-pathological and demographic data were collated alongside detailed follow-up and obstetric outcomes in conjunction with primary care and death register. RESULTS: 117 patients underwent conservative surgery for small volume stage 1B1 disease. 58 (49.5%) underwent fertility sparing conservative management with LLETZ while 59 (50.5%) underwent simple hysterectomy. Overall, 95% (111/117) of the patients underwent bilateral pelvic lymphadenectomy and 1 positive node was identified. There was no death related to cervical cancer and 1 recurrence identified during a median follow up of 8.5 years (1-20). 17 pregnancies have been recorded in patients underwent LLETZ and 17 live babies were born. No second trimester miscarriages were noted and there was one preterm delivery (36 weeks). CONCLUSION: Non-radical surgery with negative pelvic lymphadenectomy for smallvolume stage 1B1 cervical cancer ensures excellent survival without compromising obstetric outcomes. Should these results be verified by the ongoing prospective studies, radical surgery for these patients may be avoided.

Prognostic Significance of Ultrasound Characteristics and Body Mass Index in Patients with Apparent Early-Stage Cervical Cancer: A Single-Center, Retrospective, Cohort Study.

The primary aim of the present study was to investigate the prognostic impact (defined as disease-free-DFS and overall survival-OS) of the ultrasound scan tumor parameters, patients' anthropometric parameters, and their combination in early-stage cervical cancer. The secondary aim was to assess the relation between ultrasound characteristics and pathological parametrial infiltration. This is a retrospective, single-center, observational cohort study. Consecutive patients with clinical FIGO 2018 stage IA1-IB2 and IIA1 cervical cancer who underwent preoperative ultrasound examination and radical surgery between 02/2012 and 06/2019 were included. Patients who underwent neo-adjuvant treatment, fertility sparing surgery, and pre-operative conization were excluded. Data from 164 patients were analyzed. Body mass index (BMI) ≤20 Kg/m2 (p < 0.001) and ultrasound tumor volume (p = 0.038) were related to a higher risk of recurrence. The ratios between ultrasound tumor volume and BMI, ultrasound tumor volume and height, and ultrasound largest tumor diameter and BMI were significantly related to a higher risk of recurrence (p = 0.011, p = 0.031, and p = 0.017, respectively). The only anthropometric characteristic related to a higher risk of death was BMI ≤20 Kg/m2 (p = 0.021). In the multivariate analysis, the ratio between ultrasound-measured largest tumor diameter and cervix-fundus uterine diameter (with 37 as the cut-off) was significantly associated with pathological microscopic parametrial infiltration (p = 0.018). In conclusion, a low BMI was the most significant anthropometric biomarker impairing DFS and OS in patients with apparent early-stage cervical cancer. The ratios between ultrasound tumor volume and BMI, ultrasound tumor volume and height, and ultrasound largest tumor diameter and BMI significantly affected DFS but not OS. The ratio between ultrasound-measured largest tumor diameter and cervix-fundus uterine diameter was related to parametrial infiltration. These novel prognostic parameters may be useful in pre-operative workup for a patient-tailored treatment in early-stage cervical cancer.

Finding the sentinel lymph node in early cervical cancer: When is unusual not uncommon?

OBJECTIVE: To report our institutional experience with sentinel lymph node (SLN) detection using indocyanine green for cervical cancer, in terms of detection rates, detection of SLN at unusual locations, and factors associated with unusual SLN locations. In addition, we performed a systematic review of the literature to identify factors associated with unusual SLN localizations. METHODS: This is a retrospective cohort study of women with early-stage cervical cancer undergoing sentinel lymph node mapping between 2015 and 2019. Outcome measures were SLN detection rates, detection rates of unusual locations for SLN and risk factors for aberrant lymphatic drainage pathways. In addition, studies evaluating factors associated with unusual SLN locations in cervical cancer were assessed in a systematic review. RESULTS: A total of 100 patients were included. The unilateral SLN detection rate was 88%, whereas the bilateral detection rate was 75%. In 37% of all patients, SLN were found in unusual locations, and in 10% of patients SLN were solely found in unusual locations. Body mass index (BMI) was associated with finding SLN in unusual locations, with unusual nodes detected in 52% of patients with BMI <25 kg/m2 and in 28% of patients with BMI ≥25 kg/m2. The systematic review identified three studies, identifying lower BMI, nulliparity and tumor size of >20 mm as factors associated with finding SLN at unusual locations. CONCLUSION: Aberrant drainage sites represent a significant proportion of SLN detected in cervical cancer. Factors associated with increased rates of unusual nodal locations are a lower BMI, with a possible association with nulliparity and tumor size of >20 mm.

SUCCOR quality: validation of ESGO quality indicators for surgical treatment of cervical cancer.

OBJECTIVE: To evaluate whether compliance with European Society of Gynaecological Oncology (ESGO) surgery quality indicators impacts disease-free survival in patients undergoing radical hysterectomy for cervical cancer. METHODS: In this retrospective cohort study, 15 ESGO quality indicators were assessed in the SUCCOR database (patients who underwent radical hysterectomy for International Federation of Gynecology and Obstetrics (FIGO) stage 2009 IB1, FIGO 2018 IB1, and IB2 cervical cancer between January 2013 and December 2014), and the final score ranged between 0 and 16 points. Centers with more than 13 points were classified as high-quality indicator compliance centers. We constructed a weighted cohort using inverse probability weighting to adjust for the variables. We compared disease-free survival and overall survival using Cox proportional hazards regression analysis in the weighted cohort. RESULTS: A total of 838 patients were included in the study. The mean number of quality indicators compliance in this cohort was 13.6 (SD 1.45). A total of 479 (57.2%) patients were operated on at high compliance centers and 359 (42.8%) patients at low compliance centers. High compliance centers performed more open surgeries (58.4% vs 36.7%, p<0.01). Women who were operated on at centers with high compliance with quality indicators had a significantly lower risk of relapse (HR=0.39; 95% CI 0.25 to 0.61; p<0.001). The association was reduced, but remained significant, after further adjustment for conization, surgical approach, and use of manipulator surgery (HR=0.48; 95% CI 0.30 to 0.75; p=0.001) and adjustment for adjuvant therapy (HR=0.47; 95% CI 0.30 to 0.74; p=0.001). Risk of death from disease was significantly lower in women operated on at centers with high adherence to quality indicators (HR=0.43; 95% CI 0.19 to 0.97; p=0.041). However, the association was not significant after adjustment for conization, surgical approach, use of manipulator surgery, and adjuvant therapy. CONCLUSIONS: Patients with early cervical cancer who underwent radical hysterectomy in centers with high compliance with ESGO quality indicators had a lower risk of recurrence and death.

Determining the Potential of DNA Damage Response (DDR) Inhibitors in Cervical Cancer Therapy.

Cisplatin-based chemo-radiotherapy (CRT) is the standard treatment for advanced cervical cancer (CC) but the response rate is poor (46-72%) and cisplatin is nephrotoxic. Therefore, better treatment of CC is urgently needed. We have directly compared, for the first time, the cytotoxicity of four DDR inhibitors (rucaparib/PARPi, VE-821/ATRi, PF-477736/CHK1i and MK-1775/WEE1i) as single agents, and in combination with cisplatin and radiotherapy (RT) in a panel of CC cells. All inhibitors alone caused concentration-dependent cytotoxicity. Low ATM and DNA-PKcs levels were associated with greater VE-821 cytotoxicity. Cisplatin induced ATR, CHK1 and WEE1 activity in all of the cell lines. Cisplatin only activated PARP in S-phase cells, but RT activated PARP in the entire population. Rucaparib was the most potent radiosensitiser and VE-821 was the most potent chemosensitiser. VE-821, PF-47736 and MK-1775 attenuated cisplatin-induced S-phase arrest but tended to increase G2 phase accumulation. In mice, cisplatin-induced acute kidney injury was associated with oxidative stress and PARP activation and was prevented by rucaparib. Therefore, while all inhibitors investigated may increase the efficacy of CRT, the greatest clinical potential of rucaparib may be in limiting kidney damage, which is dose-limiting.

SUCCOR cone study: conization before radical hysterectomy.

OBJECTIVE: To evaluate disease-free survival of cervical conization prior to radical hysterectomy in patients with stage IB1 cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) 2009). METHODS: A multicenter retrospective observational cohort study was conducted including patients from the Surgery in Cervical Cancer Comparing Different Surgical Aproaches in Stage IB1 Cervical Cancer (SUCCOR) database with FIGO 2009 IB1 cervical carcinoma treated with radical hysterectomy between January 1, 2013, and December 31, 2014. We used propensity score matching to minimize the potential allocation biases arising from the retrospective design. Patients who underwent conization but were similar for other measured characteristics were matched 1:1 to patients from the non-cone group using a caliper width ≤0.2 standard deviations of the logit odds of the estimated propensity score. RESULTS: We obtained a weighted cohort of 374 patients (187 patients with prior conization and 187 non-conization patients). We found a 65% reduction in the risk of relapse for patients who had cervical conization prior to radical hysterectomy (hazard ratio (HR) 0.35, 95% confidence interval (CI) 0.16 to 0.75, p=0.007) and a 75% reduction in the risk of death for the same sample (HR 0.25, 95% CI 0.07 to 0.90, p=0.033). In addition, patients who underwent minimally invasive surgery without prior conization had a 5.63 times higher chance of relapse compared with those who had an open approach and previous conization (HR 5.63, 95% CI 1.64 to 19.3, p=0.006). Patients who underwent minimally invasive surgery with prior conization and those who underwent open surgery without prior conization showed no differences in relapse rates compared with those who underwent open surgery with prior cone biopsy (reference) (HR 1.94, 95% CI 0.49 to 7.76, p=0.349 and HR 2.94, 95% CI 0.80 to 10.86, p=0.106 respectively). CONCLUSIONS: In this retrospective study, patients undergoing cervical conization before radical hysterectomy had a significantly lower risk of relapse and death.

Open vs minimally invasive radical trachelectomy in early-stage cervical cancer: International Radical Trachelectomy Assessment Study.

BACKGROUND: Minimally invasive radical trachelectomy has emerged as an alternative to open radical hysterectomy for patients with early-stage cervical cancer desiring future fertility. Recent data suggest worse oncologic outcomes after minimally invasive radical hysterectomy than after open radical hysterectomy in stage I cervical cancer. OBJECTIVE: We aimed to compare 4.5-year disease-free survival after open vs minimally invasive radical trachelectomy. STUDY DESIGN: This was a collaborative, international retrospective study (International Radical Trachelectomy Assessment Study) of patients treated during 2005-2017 at 18 centers in 12 countries. Eligible patients had squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma; had a preoperative tumor size of ≤2 cm; and underwent open or minimally invasive (robotic or laparoscopic) radical trachelectomy with nodal assessment (pelvic lymphadenectomy and/or sentinel lymph node biopsy). The exclusion criteria included neoadjuvant chemotherapy or preoperative pelvic radiotherapy, previous lymphadenectomy or pelvic retroperitoneal surgery, pregnancy, stage IA1 disease with lymphovascular space invasion, aborted trachelectomy (conversion to radical hysterectomy), or vaginal approach. Surgical approach, indication, and adjuvant therapy regimen were at the discretion of the treating institution. A total of 715 patients were entered into the study database. However, 69 patients were excluded, leaving 646 in the analysis. Endpoints were the 4.5-year disease-free survival rate (primary), 4.5-year overall survival rate (secondary), and recurrence rate (secondary). Kaplan-Meier methods were used to estimate disease-free survival and overall survival. A post hoc weighted analysis was performed, comparing the recurrence rates between surgical approaches, with open surgery being considered as standard and minimally invasive surgery as experimental. RESULTS: Of 646 patients, 358 underwent open surgery, and 288 underwent minimally invasive surgery. The median (range) patient age was 32 (20-42) years for open surgery vs 31 (18-45) years for minimally invasive surgery (P=.11). Median (range) pathologic tumor size was 15 (0-31) mm for open surgery and 12 (0.8-40) mm for minimally invasive surgery (P=.33). The rates of pelvic nodal involvement were 5.3% (19 of 358 patients) for open surgery and 4.9% (14 of 288 patients) for minimally invasive surgery (P=.81). Median (range) follow-up time was 5.5 (0.20-16.70) years for open surgery and 3.1 years (0.02-11.10) years for minimally invasive surgery (P<.001). At 4.5 years, 17 of 358 patients (4.7%) with open surgery and 18 of 288 patients (6.2%) with minimally invasive surgery had recurrence (P=.40). The 4.5-year disease-free survival rates were 94.3% (95% confidence interval, 91.6-97.0) for open surgery and 91.5% (95% confidence interval, 87.6-95.6) for minimally invasive surgery (log-rank P=.37). Post hoc propensity score analysis of recurrence risk showed no difference between surgical approaches (P=.42). At 4.5 years, there were 6 disease-related deaths (open surgery, 3; minimally invasive surgery, 3) (log-rank P=.49). The 4.5-year overall survival rates were 99.2% (95% confidence interval, 97.6-99.7) for open surgery and 99.0% (95% confidence interval, 79.0-99.8) for minimally invasive surgery. CONCLUSION: The 4.5-year disease-free survival rates did not differ between open radical trachelectomy and minimally invasive radical trachelectomy. However, recurrence rates in each group were low. Ongoing prospective studies of conservative management of early-stage cervical cancer may help guide future management.

Radical hysterectomy in early cervical cancer in Europe: characteristics, outcomes and evaluation of ESGO quality indicators.

INTRODUCTION: Comprehensive updated information on cervical cancer surgical treatment in Europe is scarce. OBJECTIVE: To evaluate baseline characteristics of women with early cervical cancer and to analyze the outcomes of the ESGO quality indicators after radical hysterectomy in the SUCCOR database. METHODS: The SUCCOR database consisted of 1272 patients who underwent radical hysterectomy for stage IB1 cervical cancer (FIGO 2009) between January 2013 and December 2014. After exclusion criteria, the final sample included 1156 patients. This study first described the clinical, surgical, pathological, and follow-up variables of this population and then analyzed the outcomes (disease-free survival and overall survival) after radical hysterectomy. Surgical-related ESGO quality indicators were assessed and the accomplishment of the stated recommendations was verified. RESULTS: The mean age of the patients was 47.1 years (SD 10.8), with a mean body mass index of 25.4 kg/m2 (SD 4.9). A total of 423 (36.6%) patients had a previous cone biopsy. Tumor size (clinical examination) <2 cm was observed in 667 (57.7%) patients. The most frequent histology type was squamous carcinoma (794 (68.7%) patients), and positive lymph nodes were found in 143 (12.4%) patients. A total of 633 (54.8%) patients were operated by open abdominal surgery. Intra-operative complications occurred in 108 (9.3%) patients, and post-operative complications during the first month occurred in 249 (21.5%) patients, with bladder dysfunction as the most frequent event (119 (10.3%) patients). Clavien-Dindo grade III or higher complication occurred in 56 (4.8%) patients. A total of 510 (44.1%) patients received adjuvant therapy. After a median follow-up of 58 months (range 0-84), the 5-year disease-free survival was 88.3%, and the overall survival was 94.9%. In our population, 10 of the 11 surgical-related quality indicators currently recommended by ESGO were fully fulfilled 5 years before its implementation. CONCLUSIONS: In this European cohort, the rate of adjuvant therapy after radical hysterectomy is higher than for most similar patients reported in the literature. The majority of centers were already following the European recommendations even 5 years prior to the ESGO quality indicator implementations.

Risk of ovarian recurrence after ovarian conservation in early-stage cervical cancer treated with radical surgery: A propensity match analysis.

INTRODUCTION: The primary aim of the present study was to assess the incidence of ovarian metastasis/recurrence and the survival of patients undergoing radical hysterectomy with ovarian conservation (CONSERV) versus oophorectomy (OOPHOR). Secondary aim was to assess the incidence and the characteristics of menopausal symptoms in both groups. MATERIALS AND METHODS: Retrospective, multi-center, observational cohort study including patients <50 years with clinical FIGO 2009 stage IA1-IB1/IIA1 cervical carcinoma, treated by primary surgical treatment between 02/2007 and 07/2019. One-to-one case-control matching was used to adjust the baseline prognostic characteristics in survival analysis. RESULTS: 419 patients were included. 264 in the OOPHOR (63.0%) and 155 (37.0%) in the CONSERV group. Ovarian transposition was performed in 28/155 (18.1%) patients. 1/264 (0.4%) patient had ovarian metastasis from endocervical adenocarcinoma. After propensity-matching, 310 patients were included in the survival analysis (155 per group). 5-year disease-free survival of patients undergoing CONSERV versus OOPHOR was 90.6% versus 82.2%, respectively (p = 0.028); 5-year overall survival was 94.3% versus 90.8%, respectively (p = 0.157). Two patients (1.3%) developed recurrence on the conserved ovary. CONSERV represented an independent protective factor of recurrence (HR:0.361, 95%CI 0.169-0.769; p = 0.008). 28 (20.6%) in the CONSERV group versus 116 (60.4%) in the OOPHOR group complained of menopausal symptoms during follow up (p < 0.001). HRT was prescribed to 12.0% of patients (median HRT time was 20 months). CONCLUSION: CONSERV was associated with reduced risk of recurrence and menopausal symptoms in early-stage cervical cancer. As the risk of ovarian metastasis and ovarian recurrence is relatively low, CONSERV in pre-menopausal women has to be considered.

Protective Role of Conization Before Radical Hysterectomy in Early-Stage Cervical Cancer: A Propensity-Score Matching Study.

PURPOSE: The purpose of this study was to assess the prognostic role and the perioperative outcomes of conization performed before radical hysterectomy in early-stage cervical carcinoma. METHODS: This multicenter, retrospective observational cohort study included patients with FIGO 2009 stage IB1 cervical carcinoma treated with radical hysterectomy between June 2004 and June 2019. Patients were divided into two groups according to conization before radical surgery. One-to-one case-control matching was used to adjust the baseline characteristics. RESULTS: A total of 332 patients were included after propensity matching (166, 50% in each group). Twenty-four of 166 (14.4%) and 142 of 166 (85.6%) conization patients had negative and positive surgical margins on the conization specimen, respectively. No difference in intra- and postoperative complications was noted between the two groups (p = 0.542 and p = 0.180, respectively). Patients undergoing conization before radical hysterectomy received less adjuvant treatment (p < 0.001) and had a better 5-year disease-free survival (DFS) than patients who did not receive conization (89.8% vs. 80.0%, respectively; p = 0.010). No difference in 5-year overall survival (OS) (97.1% vs. 91.4%, respectively; p = 0.114) or recurrence pattern (p = 0.115) was reported between the two groups. Factors independently related to higher risk of recurrence were pathologic tumor diameter >20 mm and no conization before radical hysterectomy (p = 0.011 and p = 0.018, respectively). The only independent variable influencing OS was pathologic tumor diameter >20 mm (p = 0.020). CONCLUSIONS: Conization before radical hysterectomy was associated with improved DFS and lower probability of receiving adjuvant treatment. No difference in perioperative complications and OS was evident. Tumor diameter >20 mm was found to be the only independent risk factor affecting OS in both groups.

Investigating the possible impact of peritoneal tumor exposure amongst women with early stage cervical cancer treated with minimally invasive approach.

INTRODUCTION: Recent findings show a detrimental impact of the minimally invasive approach on patients with early stage cervical cancer (ECC). Reasons beyond these results are unclear. The aim of the present article is to investigate the possible role of peritoneal contamination during intracorporeal colpotomy. METHODS: patients with early stage cervical cancer were divided into 2 groups: no intraperitoneal exposure (N-IPE) intraperitoneal exposure (IPE) during minimally invasive surgery. Patients of the 2 groups were propensity-matched according to the major risk factors. RESULTS: 226 cases of the IPE group had a significant worst prognosis than the 142 cases of the N-IPE group (4.5-years disease free survival: 86.6% vs 95.9% respectively, p = 0.005), while N-IPE had similar survival to open surgery (4.5-years disease free survival: 95.0% vs 90.5% respectively, p = 0.164). Distant recurrence was more frequent among IPE patients with a borderline significance (3.5% vs 0.4% among IPE and N-IPE respectively, p = 0.083). On multivariate analysis, intraperitoneal tumor exposure was an independent prognostic factors for worse survival; patients belonging to the N-IPE group had a risk of recurrence of about 3-fold lower compared to patients of the IPE group (hazard ratio: 0.37, 95% confidence interval: 0.15-0.88, p = 0.025). CONCLUSION: it would be advisable that further prospective studies investigating the efficacy of different surgical approach in ECC take into consideration of this issue. Moreover, all other measures that could potentially prevent peritoneal exposure of tumor should be adopted during minimally invasive surgery for early stage cervical cancer to provide higher survival outcomes.

Utility of Intraoperative Fluorescence Imaging in Gynecologic Surgery: Systematic Review and Consensus Statement.

BACKGROUND: This study aimed to review the current knowledge on the utility of intraoperative fluorescence imaging in gynecologic surgery and to give evidence-based recommendations to improve the quality of care for women who undergo gynecologic surgery. METHODS: A computer-based systematic review of the MEDLINE, CENTRAL, Pubmed, EMBASE, and SciSearch databases as well as institutional guidelines was performed. The time limit was set at 2000-2019. For the literature search, PRISMA guidelines were followed. A modified-Delphi method was performed in three rounds by a panel of experts to reach a consensus of conclusions and recommendations. RESULTS: Indocyanine green (ICG) is used primarily in gynecology for sentinel node-mapping. In endometrial and cervical cancer, ICG is a feasible, safe, time-efficient, and reliable method for lymphatic mapping, with better bilateral detection rates. Experience in vulvar cancer is more limited, with ICG used together with Tc-99 m as a dual tracer and alone in video endoscopic inguinal lymphadenectomy. In early ovarian cancer, results are still preliminary but promising. Indocyanine green fluorescence imaging also is used for ureteral assessment, allowing intraoperative ureteral visualization, to reduce the risk of ureteral injury during gynecologic surgery. CONCLUSIONS: For most gynecologic cancers, ICG fluorescence imaging is considered the tracer of choice for lymphatic mapping. The use of this new technology expands to a better ureteral assessment.

SUCCOR study: an international European cohort observational study comparing minimally invasive surgery versus open abdominal radical hysterectomy in patients with stage IB1 cervical cancer.

BACKGROUND: Minimally invasive surgery in cervical cancer has demonstrated in recent publications worse outcomes than open surgery. The primary objective of the SUCCOR study, a European, multicenter, retrospective, observational cohort study was to evaluate disease-free survival in patients with stage IB1 (FIGO 2009) cervical cancer undergoing open vs minimally invasive radical hysterectomy. As a secondary objective, we aimed to investigate the association between protective surgical maneuvers and the risk of relapse. METHODS: We obtained data from 1272 patients that underwent a radical hysterectomy by open or minimally invasive surgery for stage IB1 cervical cancer (FIGO 2009) from January 2013 to December 2014. After applying all the inclusion-exclusion criteria, we used an inverse probability weighting to construct a weighted cohort of 693 patients to compare outcomes (minimally invasive surgery vs open). The first endpoint compared disease-free survival at 4.5 years in both groups. Secondary endpoints compared overall survival among groups and the impact of the use of a uterine manipulator and protective closure of the colpotomy over the tumor in the minimally invasive surgery group. RESULTS: Mean age was 48.3 years (range; 23-83) while the mean BMI was 25.7 kg/m2 (range; 15-49). The risk of recurrence for patients who underwent minimally invasive surgery was twice as high as that in the open surgery group (HR, 2.07; 95% CI, 1.35 to 3.15; P=0.001). Similarly, the risk of death was 2.42-times higher than in the open surgery group (HR, 2.45; 95% CI, 1.30 to 4.60, P=0.005). Patients that underwent minimally invasive surgery using a uterine manipulator had a 2.76-times higher hazard of relapse (HR, 2.76; 95% CI, 1.75 to 4.33; P<0.001) and those without the use of a uterine manipulator had similar disease-free-survival to the open surgery group (HR, 1.58; 95% CI, 0.79 to 3.15; P=0.20). Moreover, patients that underwent minimally invasive surgery with protective vaginal closure had similar rates of relapse to those who underwent open surgery (HR, 0.63; 95% CI, 0.15 to 2.59; P<0.52). CONCLUSIONS: Minimally invasive surgery in cervical cancer increased the risk of relapse and death compared with open surgery. In this study, avoiding the uterine manipulator and using maneuvers to avoid tumor spread at the time of colpotomy in minimally invasive surgery was associated with similar outcomes to open surgery. Further prospective studies are warranted.

BRAF Wild-type, PTEN Mutant Malignant Uveal Melanoma Arising Within a Mature Ovarian Teratoma: A Case Report and Review of the Literature.

Mature cystic teratomas are common in women of all ages; however, malignant transformation within them is rare and difficult to diagnosis preoperatively. Primary melanoma of the ovary is exceptionally rare and only occurs in relation to a teratoma where it can originate from sporadic somatic mutagenesis within epidermal junctional melanocytes, through malignant transformation of a benign nevus formed within the mature cystic teratoma or from other well differentiated pigment-containing structures such as the uvea. We present a case of primary malignant melanoma arising within a mature cystic teratoma in a young patient, who ultimately developed widespread metastasis necessitating systemic therapy. Our case highlights the role of molecular medicine not only in forming an understanding the origin of the melanoma, but also guiding targeted systemic therapies. Alongside the case we present a review of the literature describing the incidence of molecular aberrations within melanoma as well as the established and emerging techniques and cytotoxic agents for malignant melanoma.

International radical trachelectomy assessment: IRTA study.

BACKGROUND: Radical trachelectomy is considered a viable option for fertility preservation in patients with low-risk, early-stage cervical cancer. Standard approaches include laparotomy or minimally invasive surgery when performing radical trachelectomy. PRIMARY OBJECTIVE: To compare disease-free survival between patients with FIGO (2009) stage IA2 or IB1 (≤2cm) cervical cancer who underwent open versus minimally invasive (laparoscopic or robotic) radical trachelectomy. STUDY HYPOTHESIS: We hypothesize that minimally invasive radical trachelectomy has similar oncologic outcomes to those of the open approach. STUDY DESIGN: This is a collaborative, multi-institutional, international, retrospective study. Patients who underwent a radical trachelectomy and lymphadenectomy between January 1, 2005 and December 31, 2017 will be included. Institutional review board approval will be required. Each institution will be provided access to a study-specific REDCap (Research Electronic Data Capture) database maintained by MD Anderson Cancer Center and will be responsible for entering patient data. INCLUSION CRITERIA: Patients with squamous, adenocarcinoma, or adenosquamous cervical cancer FIGO (2009) stages IA2 and IB1 (≤2 cm) will be included. Surgery performed by the open approach or minimally invasive approach (laparoscopy or robotics). Tumor size ≤2 cm, by physical examination, ultrasound, MRI, CT, or positron emission tomography (at least one should confirm a tumor size ≤2 cm). Centers must contribute at least 15 cases of radical trachelectomy (open, minimally invasive, or both). EXCLUSION CRITERIA: Prior neoadjuvant chemotherapy or radiotherapy to the pelvis for cervical cancer at any time, prior lymphadenectomy, or pelvic retroperitoneal surgery, pregnant patients, aborted trachelectomy (intra-operative conversion to radical hysterectomy), or vaginal approach. PRIMARY ENDPOINT: The primary endpoint is disease-free survival measured as the time from surgery until recurrence or death due to disease. To evaluate the primary objective, we will compare disease-free survival among patients with FIGO (2009) stage IA2 or IB1 (≤2cm) cervical cancer who underwent open versus minimally invasive radical trachelectomy. SAMPLE SIZE: An estimated 535 patients will be included; 256 open and 279 minimally invasive radical trachelectomy. Previous studies have shown that recurrence rates in the open group range from 3.8% to 7.6%. Assuming that the 4.5-year disease-free survival rate for patients who underwent open surgery is 95.0%, we have 80% power to detect a 0.44 HR using α level 0.10. This corresponds to an 89.0% disease-free survival rate at 4.5 years in the minimally invasive group.

Laterally Extended Pelvic Resection for Gynaecological Malignancies: A Multicentric Experience with Out-of-the-Box Surgery.

PURPOSE: To evaluate morbidity and oncological outcome in a multicentre series of women with gynaecological malignancies infiltrating pelvic side wall (PSW) that received laterally extended pelvic resection (LEPR). METHODS: Patients operated between 2007 and 2017 at three institutions were included. LEPR was defined as an en bloc lateral resection of a pelvic tumour involving sidewall muscle, and/or bone, and/or major nerve, and/or major vascular structure. Postsurgical complications and survivals were evaluated. RESULTS: Sixty-three women with gynaecological tumours involving PSW were treated with LEPR. Five women underwent primary LEPR, whereas 58 (92%) patients needed LEPR because of recurrence. Twenty-four women (38%) received previous radiation therapy before the surgery. R0 resection was achieved in 54 patients (85.7%), whereas the pathologic margins were microscopically and macroscopically positive in 8 (12.7%) patients and 1 (1.6%) patient, respectively. There was one perioperative death, whereas major postoperative complications occurred in 17 patients (27.7%). Thirty (47.5%) women experienced recurrences: 24/54 (44.4%) were in the R0 group, and 6/9 (66.6%) were in the R1 group, with a median PFS of 15 months and 7 months, respectively (p = 0.024). In total, 11 of 54 (20.3%) patients died of disease in the R0 group and 5 of 9 (55.5%) in the R1 group; a median OS was not reached and was 32 months for R0 and R1 groups, respectively (p = 0.033). CONCLUSIONS: Involvement of the PSW should not prevent obtaining R0 resection. Although the LEPR is associated with considerable morbidity (≈ 30%), a long-term survival seems to be achieved in those women with complete resection.

Indocyanine green-assisted parametrial dissection during type C1 radical hysterectomy after sentinel lymph node biopsy in early stage cervical cancer.

OBJECTIVES: The standard treatment for FIGO stage 1B1 cervical cancer is radical hysterectomy (RH) [1]. Indocyanine-green (ICG) is a drug injected within the cervical stroma to detect the sentinel lymph node (SLN) in cervical cancer [2,3]. ICG travels through the lymphatic channels in the lateral parametrium, which results enhanced with green, before reaching the SLNs. This could help identifying the surgical landmarks. The aim of this video is to propose a new approach to perform parametrial dissection as part of RH under the guidance of ICG. METHODS: The patient was a 49-years old woman diagnosed with a FIGO 1B1 moderately-differentiated cervical squamous cell carcinoma. No evidence of lymphoadenopathy on pre-operative imaging. 0.25ml of ICG (1.25mg/ml) were injected superficially and deep at 3 and 9 o'clock in the cervix as first step of the operation. Bilateral SLN biopsy followed by type C1 RH with bilateral salpingo-oophorectomy and bilateral pelvic node dissection was performed. Near-infrared camera (PINPOINT® - Novadaq Technologies) was used during parametrial dissection. RESULTS: ICG was used as a guide to demarcate the parametrial tissue and assist the dissection of the lateral (paracervix) and anterior (vesico-uterine ligament) parametrium off the surrounding structures (bladder and ureter). Operation time was 150min and intraoperative estimated blood loss was 50 mls. No intraoperative or postoperative complication was reported. CONCLUSIONS: ICG-assisted parametrial dissection during RH after SLN biopsy in early stage cervical cancer can be a useful tool to guide the surgeon to perform the procedure and potentially improve surgical outcomes.

Short- and long-term outcomes following pelvic exenteration for gynae-oncological and colorectal cancers: A 9 year consecutive single-centre cohort study.

OBJECTIVES: Radical pelvic exenteration can be undertaken for locally invasive or recurrent disease in both colorectal and gynaecological malignancies. In the UK this procedure is usually undertaken by the respective surgical specialties who have undergone divergent surgical training. This study describes and compares outcomes between colorectal and gynae-oncological teams following pelvic exenteration for primary and recurrent gynaecological and colorectal cancers in a single-centre multi-disciplinary team. METHOD: A retrospective review of consecutive pelvic exenteration patients undertaken over a nine-year period in a tertiary referral centre. Analyses comparing short- and long-term morbidity and mortality outcomes were undertaken by chi-square test for categorical variables and Mann-Whitney U for continuous variables. Cumulative survival rates were calculated according to the Kaplan-Meier method and factors associated with recurrence and survival determined using a Cox regression model. RESULTS: Thirty-four exenterations were undertaken; fourteen colorectal and twenty gynae-oncological. Morbidity was seen in 50% of colorectal and 75% of gynae-oncological patients. Recurrence was seen earlier and with greater frequency in the gynaeoncology group (44.4% and median time 11 months) than the colorectal group (21.4%, median time 41 months; p > 0.05). Survival in the gynae-oncology group was also lower than the colorectal group at 1-year (69.6% vs. 92.9%) and 5-years (58.0% vs. 92.9%; p = 0.115). The majority of gynae-oncological mortality occurred within 3-years of surgery, whilst the majority of mortality in the colorectal group was after 5-years. CONCLUSION: Long-term patient outcome measures, including disease recurrence and 5-year survival, for colorectal exenteration appear better than for gynaeoncology patients, however, no statistical significant difference exists between short-term outcome measures between specialties. This is likely to be caused by different baseline pathologies and disease pattern influencing longer term prognosis but may also be a function of differing surgical thresholds and patient selection bias between specialties. Peri-operative and short-term morbidity appear equivalent despite divergent surgical backgrounds and training.

Poly(ADP-Ribose) Polymerase in Cervical Cancer Pathogenesis: Mechanism and Potential Role for PARP Inhibitors.

Treatment options for disease recurrence of women treated for locally advanced and advanced cervical cancer are very limited-largely palliative chemotherapy. The low efficacy of the currently available drugs raises the need for new targeted agents. Poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors (PARPi) have emerged as a promising class of chemotherapeutic agents in cancers associated with defects in DNA repair. Their therapeutic potential in cervical cancer is currently being evaluated in 3 ongoing clinical trials. Here we review the available information regarding all the aspects of PARP in cervical intraepithelial neoplasia and invasive cervical cancer, from expression and the mechanism of action to the role of the polymorphisms in the pathogenesis of the disease, as well as the potential of the inhibitors. We finally propose a new unifying theory regarding the role of PARPs in the development of cervical carcinomas.