Clinical outcomes of BRCA1/2 pathogenic variants in ovarian cancer cluster region in patients with primary peritoneal, epithelial ovarian, and fallopian tube cancer.

OBJECTIVE: An "ovarian cancer cluster region" (OCCR) has been reported in both BRCA1 and BRCA2. However, the clinical significance of the OCCR of BRCA1/2 has not yet been investigated. METHODS: The medical records of 991 patients with epithelial ovarian, primary peritoneal, and fallopian tube cancer who underwent genetic testing for BRCA1 and/or BRCA2 from January 1, 2006, to August 31, 2019, were retrospectively reviewed. Sanger and next-generation sequencing analyses were used to test the BRCA1 and BRCA2 mutation status. Progression-free survival (PFS) and overall survival (OS) were compared according to the mutation location (OCCR vs. non-OCCR region). Survival outcomes were determined using Kaplan-Meier survival analysis. RESULTS: A total of 162 patients had BRCA1 pathogenic variants (PVs), and 76 had BRCA2 PVs. Patients with BRCA1 PV that in the OCCR region showed shorter PFS than those with BRCA1 PV outside the OCCR (22.6 months vs. 27.6 months, P = 0.038). In the platinum-sensitive subgroup of BRCA1, patients with BRCA1 PV in the OCCR region showed shorter PFS than those in the non-OCCR group (P = 0.0197). On the other hand, BRCA2 variants did not exhibit any particular trend (32.8 months vs. 27.9 months, P = 0.468). However, no significant differences were detected in OS between patients with BRCA1/2 PVs, regardless of the location of the variants. CONCLUSIONS: Patients with BRCA1 PV in the OCCR had shorter PFS than those outside the OCCR. This tendency was more pronounced in the platinum-sensitive subgroup. To our knowledge, this is the first study of BRCA1/2 mutations based on the OCCR.

Long term oncologic and reproductive outcomes after robot-assisted radical trachelectomy for early-stage cervical cancer. An international multicenter study.

OBJECTIVES: Long term outcomes following fertility sparing robot-assisted radical trachelectomy (RRT). METHODS: A retrospective study of consecutive women selected for RRT between 2007 and 2019 at five referral centres. Generally used selection criteria for fertility-sparing surgery were applied. Oncologic, reproductive and long-term clinical data were analysed. RESULTS: Of the 166 included women, 149 completed a RRT. Median tumor size was 9 mm (range 3-20 mm), 111 women (75%) had FIGO 2009 stage IB1 cancer and 4.8% were node positive. At a median follow up of 58 months, 12 of all women (7.2%) and 9 of 149 women (6%) who underwent completed RRT with fertility preservation had recurred and two had died. 70 of 88 women (80%) who attempted to conceive succeeded, resulting in 81 pregnancies that progressed beyond the first trimester and 76 live births of which 54 (70%) were delivered at term and 65 (86%) delivered after gestational week 32. A short postoperative cervical length was associated with impaired fertility. A late secondary hysterectomy was necessary in four women due to persistent bleeding (n = 2), hematometra due to a cervical stenosis (n = 1) and recurrent dysplasia (n = 1). CONCLUSION: In this long-term follow-up of RRT the recurrence rate is comparable to larger individual studies of minimally invasive or vaginal radical trachelectomy with similar risk profile and follow up. The high pregnancy rate and low rate of premature delivery before 32 weeks GA may promote the use of robot-assisted approach.

Markedly increased risk of malignancies in women with endometriosis.

OBJECTIVE: To assess the cancer risk in a cohort of women with newly diagnosed endometriosis. METHODS: This retrospective, nationwide, population-based cohort study utilized data from the 10-year claims database of the Korean National Health Insurance from January 2008 to December 2018. Patients diagnosed with endometriosis between 2010 and 2013 were included; those who underwent appendectomy but were not diagnosed with endometriosis during the study period served as controls. No participant was diagnosed with cancer before enrollment. Cancer diagnoses according to the International Classification of Diseases, 10th revision, were compared between the two groups. Cancer occurrence in both groups was identified according to the diagnostic codes for different organ sites. RESULTS: Altogether, 179,865 patients with endometriosis and 87,408 controls were analyzed, and the incidence rates of cancer were 644.3 and 543.8 per 100,000 person-years, respectively. Patients with endometriosis had a significantly increased overall cancer risk (hazard ratio [HR], 1.34; 95% confidence interval [CI], 1.28-1.40; p < 0.001) than controls after adjusting for age, insurance type, and comorbidities. They had significantly increased uterine (HR, 4.59; 95% CI, 3.56-5.91; p < 0.001), ovarian (HR, 2.51; 95% CI, 1.99-3.16; p < 0.001), cervical (HR, 1.84; 95% CI, 1.49-2.28; p < 0.001), breast (HR, 1.44; 95% CI, 1.31-1.58; p < 0.001), and thyroid cancer (HR, 1.34; 95% CI, 1.24-1.45; p < 0.001) risk. Median age at diagnosis was <50 years for all cancer types. CONCLUSIONS: Endometriosis was associated with an increased cancer risk, specifically uterine, ovarian, cervical, breast, and thyroid cancers, suggesting that effective cancer screening for early detection of malignancies in women should be implemented in those with endometriosis.

The preventive effect of breastfeeding against ovarian cancer in BRCA1 and BRCA2 mutation carriers: A systematic review and meta-analysis.

OBJECTIVE: A recent study showed that even a few months of breastfeeding is associated with a significant decrease in the risk of ovarian cancer in the general population. This study aimed to perform a systematic review and meta-analysis to determine the significance of the length of the breastfeeding period on ovarian cancer risk in BRCA1/2 mutation carriers. METHODS: PubMed, EMBASE, and Cochrane databases were searched up to June 1, 2021. We included case-control and cohort studies that contained information on breastfeeding and the risk of ovarian cancer in BRCA1/2 mutation carriers. Odds ratios (OR) were meta-analytically pooled using a fixed-effects model.dd RESULTS: Five studies, including one cohort study and four case-control studies, were included in this meta-analysis. Of the 14,601 BRCA1/2 mutation carriers, the overall pooled OR of ever having performed breastfeeding in patients who had ovarian cancer was 0.767 (95% confidence interval [CI], 0.688-0.856) and 0.817 (95% CI, 0.650-1.028) for patients with BRCA1 and BRCA2 mutation, respectively. Breastfeeding for >1 year acted as a protective factor in both BRCA1 [OR: 0.787 (95% CI, 0.682-0.907)] and BRCA2 [OR: 0.567 (95% CI, 0.400-0.802)] mutation carriers. No significant heterogeneity was present (I2 = 0%), and the funnel plot was also properly distributed, showing no publication bias. CONCLUSIONS: Breastfeeding is a preventive, modifiable factor for ovarian cancer in BRCA1/2 mutation carriers. Ever having performed breastfeeding was significantly preventive for ovarian cancer in the BRCA1 mutation carriers, however a period of 1 year or more of breastfeeding is required for a reduced ovarian cancer risk in BRCA2 mutation carriers.

Mutation landscape of germline and somatic BRCA1/2 in patients with high-grade serous ovarian cancer.

BACKGROUND: Poly (ADP-ribose) polymerase inhibitors targeting BRCA1/2 mutations are available for treating patients with high-grade serous ovarian cancer. These treatments may be more appropriately directed to patients who might respond if the tumor tissue is additionally tested by next-generation sequencing with a multi-gene panel and Sanger sequencing of a blood sample. In this study, we compared the results obtained using the next-generation sequencing multi-gene panel to a known germline BRCA1/2 mutational state determined by conventional Sanger sequencing to evaluate the landscape of somatic mutations in high-grade serous ovarian cancer tumors. METHODS: Cancer tissue from 98 patients with high-grade serous ovarian cancer who underwent Sanger sequencing for germline BRCA1/2 analysis were consecutively analyzed for somatic mutations using a next-generation sequencing 170-gene panel. RESULTS: Twenty-four patients (24.5%) showed overall BRCA1/2 mutations. Seven patients (7.1%) contained only somatic BRCA1/2 mutations with wild-type germline BRCA1/2, indicating acquired mutation of BRCA1/2. Three patients (3.1%) showed reversion of germline BRCA1 mutations. Among the 14 patients (14.3%) with both germline and somatic mutations in BRCA1/2, two patients showed different variations of BRCA1/2 mutations. The next-generation sequencing panel test for somatic mutation detected other pathogenic variations including RAD51D and ARID1A, which are possible targets of poly (ADP-ribose) polymerase inhibitors. Compared to conventional Sanger sequencing alone, next-generation sequencing-based tissue analysis increased the number of candidates for poly (ADP-ribose) polymerase inhibitor treatment from 17.3% (17/98) to 26.5% (26/98). CONCLUSIONS: Somatic mutation analysis by next-generation sequencing, in addition to germline BRCA1/2 mutation analysis, should become the standard of care for managing women with high-grade serous ovarian cancer to widen the indication of poly (ADP-ribose) polymerase inhibitors.

The institutional learning curve is associated with survival outcomes of robotic radical hysterectomy for early-stage cervical cancer-a retrospective study.

BACKGROUND: Despite recent advances in diagnosis and treatment, cervical cancer continues to be a significant health problem worldwide. Whereas robot-assisted surgery has advantages over the abdominal approach, and minimally invasive techniques are being used increasingly, these may be associated with a higher recurrence rate and lower overall survival than the abdominal approach. The objective of this study was to compare the surgical and survival outcomes between abdominal radical hysterectomy (ARH) and robotic radical hysterectomy (RRH). METHODS: A retrospective cohort of patients undergoing radical hysterectomy for cervical cancer from 2006 to 2018 was identified. Patients with stage IA to IB cervical cancer were included and grouped: ARH vs. RRH. The RRH group was further divided into two groups based on the year of enrollment: RRH1 (2006-2012) and RRH2 (2013-2018). Tumor characteristics, recurrence rate, progression-free survival (PFS), and overall survival (OS) were compared between the groups. P-values < 0.05 (two-sided) were considered statistically significant. RESULTS: A total of 310 patients were identified: 142 and 168 underwent ARH and RRH, respectively. RRH1 and RRH2 had 77 and 91 patients, respectively. Interestingly, RRH2 was more likely to have a larger tumor size (1.7 ± 1.4 vs. 2.0 ± 1.1 vs. 2.4 ± 1.7 cm, P = 0.014) and higher stage (P < 0.001) than RRH1. However, RRH2 showed significantly favorable PFS in contrast to RRH1. There was no difference between ARH and RRH2 in PFS (P = 0.629), whereas overall, the RRH group showed significantly shorter PFS than the ARH group. In the multivariate analysis, the institutional learning curve represented by the operation year was one of the significant predictors for PFS (hazard ratio [HR] 0.065, P = 0.0162), along with tumor size (HR 5.651, P = 0.0241). CONCLUSIONS: The institutional learning curve, represented by the operation year, is one of the most significant factors associated with outcomes of RRH for early-stage cervical cancer.

Comparison of outcomes between the one-step and two-step sentinel lymph node mapping techniques in endometrial cancer.

INTRODUCTION: Fluorescence image-guided sentinel lymph node (SLN) biopsy using a two-step mapping technique incorporates sequential injection of indocyanine green into the bilateral uterine cornus, followed by cervical injection. Outcomes were compared with the conventional cervical (one-step) method . METHODS: Patients with FIGO stage I-III endometrial cancer who underwent laparoscopic or robotic staging, including SLN biopsy, from May 2014 to December 2018, were retrospectively reviewed. Patient characteristics, pre-operative imaging, SLN detection pattern, pathologic result, adjuvant, and recurrence locations were analyzed. RESULTS: A total of 199 patients received one-step (n=123) and two-step (n=76) SLN biopsy. Para-aortic SLN were more frequently identified in the two-step group. Lower and upper para-aortic SLN were identified in 67.1% and 38.2%, respectively, in the two-step group and in 18.7% and 5.7% in the one-step group (p<0.001). The number of para-aortic SLN harvested was superior in the two-step group (p<0.001). Metastatic para-aortic SLN were found in 7.9% of the two-step group and 2.4% of the one-step group (p=0.070). In detecting nodal metastasis, the sensitivities of the one- and two-step methods were 91.7% and 100.0%, negative predictive values were 99.0% and 100.0%, false-negative rates were 8.3% and 0%, and accuracy rates were 99.1% and 100.0%, respectively. The one-step method identified only three out of eight para-aortic lymph node metastases and missed five para-aortic lymph node metastases. There was no missed para-aortic lymph node metastasis in the two-step group. Recurrence was observed in two patients (2.6%; vaginal vault and adrenal gland) in the two-step group and seven patients (5.7%) including three nodal recurrences in the one-step group (p=0.307). DISCUSSION: Two-step SLN mapping improved the para-aortic SLN detection rate, a known pitfall of conventional cervical injection. Proper evaluation of aortic nodal status will assist in the tailoring of adjuvant and prevent undertreatment of patients with isolated para-aortic metastasis.

E2F8 Induces Cell Proliferation and Invasion through the Epithelial-Mesenchymal Transition and Notch Signaling Pathways in Ovarian Cancer.

BACKGROUND: Despite the recent research implicating E2F8 (E2F Transcription Factor 8) in cancer, the role of E2F8 in the progression of ovarian cancer has remained unclear. Hence, we explored the bio-functional effects of E2F8 knockdown on ovarian cancer cell lines in vitro and in vivo. METHODS: The expression of E2F8 was compared between ovarian cancer and noncancer tissues, and its association with the progression-free survival of ovarian cancer patients was analyzed. To demonstrate the function of E2F8 in cell proliferation, migration, and invasion, we employed RNA interference to suppress E2F8 expression in ovarian cancer cell lines. Finally, the effect of E2F8 knockdown was investigated in a xenograft mouse model of ovarian cancer. RESULTS: Ovarian cancer tissue exhibited significantly higher E2F8 expression compared to that of normal ovarian tissue. Clinical data showed that E2F8 was a significant predictor of progression-free survival. Moreover, the prognosis of the ovarian cancer patients with high E2F8 expression was poorer than that of the patients with low E2F8 expression. In vitro experiments using E2F8-knockdown ovarian cancer cell lines demonstrated that E2F8 knockdown inhibited cell proliferation, migration, and tumor invasion. Additionally, E2F8 was a potent inducer and modulator of the expression of epithelial-mesenchymal transition and Notch signaling pathway-related markers. We confirmed the function of E2F8 in vivo, signifying that E2F8 knockdown was significantly correlated with reduced tumor size and weight. CONCLUSIONS: Our findings indicate that E2F8 is highly correlated with ovarian cancer progression. Hence, E2F8 can be utilized as a prognostic marker and therapeutic target against ovarian malignancy.

MicroRNA-630 inhibitor sensitizes chemoresistant ovarian cancer to chemotherapy by enhancing apoptosis.

MicroRNA-630 (miR-630) has been implicated in the development and progression of multiple cancers. The current study aimed to investigate the role of miR-630 in chemoresistant epithelial ovarian cancer. MiR-630 expression levels were detected in ovarian cancer cell line SKOV3 and paclitaxel-resistant SKOV3 (SKOV3-TR) via microarray and qRT-PCR. MiR-630 inhibitors and negative controls were transfected into SKOV3 and SKOV3-TR cells. Wound healing, invasion, chemosensitivity, and cell apoptosis assays were performed to determine proliferation and migration rates. Chemoresistant patient-derived xenograft (PDX) models were established and utilized to verify the effect of miR-630 on chemoresistant ovarian cancer. Inhibition of miR-630 decreased cell proliferation and enhanced the sensitivity of SKOV3-TR and SKOV3 cells to paclitaxel. In the chemosensitivity assay, we observed that the miR-630 inhibitor exhibited a synergistic effect with paclitaxel on SKOV3-TR cells. Inhibition was correlated with enhanced expression of apoptosis-related proteins. APAF-1 was predicted to be a potential target of miR-630. An in vivo PDX study showed that the miR-630 inhibitor sensitized chemoresistant ovarian cancer to paclitaxel. Thus, miR-630 inhibitor sensitizes chemoresistant epithelial ovarian cancer to chemotherapy by enhancing apoptosis. Our findings suggest that miR-630 might be a potential therapeutic target for chemotherapy-resistant ovarian cancer.

Perioperative Outcomes of 3-Arm Versus 4-Arm Robotic Radical Hysterectomy in Patients with Cervical Cancer.

STUDY OBJECTIVE: To investigate and compare surgical outcomes of the 3 versus 4 robotic arm approaches for robotic surgery in patients with cervical cancer. DESIGN: A retrospective analysis of prospectively collected data (Canadian Task Force classification II-2). SETTING: An academic tertiary hospital. PATIENTS: A total of 142 patients with stage 1A1 to IIB cervical carcinoma who underwent robotic surgery were included for analysis. The subjects were divided according to the surgical approach (i.e., the number of robotic arms), and the 2 groups were compared in terms of intraoperative data and postoperative outcomes. INTERVENTIONS: Robotic radical hysterectomy (RRH) with lymphadenectomy using 3 robotic arms (n = 101) versus 4 robotic arms (n = 41). MEASUREMENTS AND MAIN RESULTS: Perioperative surgical outcomes. The 3-arm robotic approach consisted of a camera arm, 2 robotic arms, and 1 conventional assistant port. An additional robotic arm was placed on the right side of the patient's abdomen for the 4-arm robotic approach. The mean age, body mass index, cell type, Fédération Internationale de Gynécologie et d'Obstétrique stage, and type of surgery were not significantly different between the 2 cohorts. The 3-arm approach showed favorable outcomes over the 4-arm approach in terms of postoperative pain at 6 and 24 hours (3.8 ± 1.8 vs 4.5 ± 1.7 and 2.8 ± 1.7 vs 3.4 ± 1.6, respectively; p = .033 and .049) and postoperative hemoglobin difference (1.8 ± 0.9 vs 2.6 ± 1.3 and 1.9 ± 1.1 vs 2.4 ± 0.9 on days 1 and 3, respectively; p = .002 and .004). The median length of postoperative hospital stay, total operative time, docking time, lymph node yield, and intraoperative and postoperative complication rates were comparable between the 2 cohorts. CONCLUSION: Surgical outcomes and complications rates of RRH for cervical cancer using the 4-arm approach were comparable with that of the 3-arm approach with decreased early postoperative pain in the 3-arm group. Cost-benefit analysis and the impact on surgical training are needed in the future.

Periumbilical infiltration of lidocaine with epinephrine for postoperative pain reduction in single-port laparoscopic adnexal surgery.

An efficient and simple approach to control postoperative pain in transumbilical single-port laparoscopic surgery appears necessary. We conducted a retrospective analysis in a study group (80 patients who received periumbilical infiltration of lidocaine with epinephrine before their incisional site repair completion) and control group (80 patients who received no analgesic at their incisional site repair completion) matched for their age, body mass index and their frequency of previous abdominal surgery. The pain scores based on the numerical rating scale (NRS) and the analgesic use frequency during the postoperative period were evaluated. The postoperative pain scores based on the NRS were significantly lower in the study group than in the control group immediately after the operation and at postoperative 6 hours. The postoperative analgesic use frequency during the hospital stay and the pain scores at 24 and 48 hours were not significantly different between the two groups. Periumbilical infiltration of lidocaine with epinephrine can reduce surgical pain until 6 hours, postoperatively. Impact statement What is already known on this subject? No consensus on whether single port laparoscopic surgery significantly reduces postoperative pain, as compared to conventional laparoscopy exists, and the immediate postoperative pain seems to be severe even with the SPL surgery. What do the results of this study add? The periumbilical infiltration of lidocaine with epinephrine can alleviate surgical pain until 6 hours, postoperatively. What are the implications of these findings for clinical practice and/or further research? Our result may provide an efficient and simple approach to control postoperative pain in a single port laparoscopic surgery.

A novel algorithm for the treatment strategy for advanced epithelial ovarian cancer: consecutive imaging, frailty assessment, and diagnostic laparoscopy.

BACKGROUND: This study aimed to evaluate the perioperative outcomes and prognostic impact of the consecutive steps of imaging, frailty assessment, and diagnostic laparoscopy (DLS) in patients with advanced epithelial ovarian cancer (EOC). METHODS: Patients diagnosed with EOC during 2012-2015 were analyzed retrospectively. Surgical and survival outcomes were compared between three treatment groups: patients without high tumor dissemination (HTD) who underwent primary debulking surgery (PDS group); patients with HTD who underwent DLS (DLS group); and patients with HTD diagnosed by cytological confirmation of malignancy followed by neoadjuvant chemotherapy (NACT group). RESULTS: Of 181 patients, 85, 38, and 58 underwent PDS, DLS, and NACT, respectively. Among the 38 consecutive patients who initially underwent DLS, 6 were considered suitable for PDS; the remaining 32 were eligible for NACT followed by interval debulking surgery. The median operative times of debulking surgery in the PDS, DLS, and NACT groups were 365 min (interquartile range [IQR]: 216.5-476.5 min), 266.2 min (IQR: 160.3-193.5 min), and 339.0 min (IQR: 205-425 min; P = 0.042), respectively, with respective median estimated blood loss volumes of 962.2 mL (IQR: 300-1037.5 mL), 267.1 mL (IQR: 150-450 mL), and 861.7 mL (IQR: 150-1200 mL; P = 0.023). The DLS group had significantly reduced transfusion requirements and intensive care unit admission rates (P = 0.006). The Kaplan-Meier survival analysis indicated significantly poor PFS in the NACT group. However, there was no significant difference in OS among the three groups. CONCLUSIONS: The consecutive steps of imaging, frailty assessment, and DLS might facilitate rapid assessments of peritoneal disease extent and resectability; this novel algorithm might also be used to individualize treatment.

BRCA1 and BRCA2 mutation predictions using the BRCAPRO and Myriad models in Korean ovarian cancer patients.

OBJECTIVE: To evaluate the predictive efficacies including sensitivity and positive predictive value of the genetic risk prediction model BRCAPRO and the Myriad BRCA risk calculator in Korean ovarian cancer patients. METHODS: Individuals undergoing genetic testing for BRCA mutations from November 2010-August 2016 were recruited from the Department of Obstetrics and Gynecology at a single institute in Korea. The observed BRCA1 and BRCA2 mutation statuses were compared with the predicted carrier probabilities using BRCAPRO and the Myriad BRCA risk calculator. RESULTS: Two hundred thirty-two patients were recruited, of whom 99.1% (230/232) were of Korean ethnicity. Of the 232 individuals, 206 and 26 had ovarian and double primary breast/ovarian cancer, respectively. Thirty-six individuals had a family history of breast/ovarian cancer in first-degree relatives. Fifty-seven patients (24.6%) tested positive for BRCA mutation (41 BRCA1, 16 BRCA2). The mean BRCAPRO and Myriad scores for all patients were 6.4% and 7.7%, respectively. The scores were significantly higher for patients with positive BRCA mutation status (29.0% vs. 6.1%, P<0.001, 12.1% vs. 7.7%, P<0.001, respectively). For all patients, the respective areas under the receiver operating characteristics curves were 0.720 and 0.747 for the BRCAPRO and Myriad models to predict the risk of carrying a BRCA mutation. Both models overestimated the mutation probability in patients with a family history of breast/ovarian cancer (1.55-fold and 1.50-fold, respectively) and underestimated the probability in patients without a family history (both, 0.54-fold). CONCLUSION: BRCAPRO and Myriad seem to be acceptable risk assessment tools for determining the risk of carrying BRCA mutations in Korean ovarian cancer patients.

The efficacy of systematic lymph node dissection in advanced epithelial ovarian cancer during interval debulking surgery performed after neoadjuvant chemotherapy.

BACKGROUND AND OBJECTIVE: The therapeutic role of systematic lymph node dissection (LND) remains unclear in advanced epithelial ovarian cancer (EOC), especially during interval debulking surgery (IDS) performed after neoadjuvant chemotherapy (NAC). We analyzed the therapeutic and prognostic roles of systematic LND in advanced EOC patients. METHODS: Data from consecutive patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC-IV disease, who underwent optimal IDS (<1cm) after NAC, were obtained via a retrospective chart review. Patients were classified into a lymph node sampling (LNS; node count <20) group and an LND (node count ≥20) group. RESULTS: Among 133 study patients, 65 and 68 underwent LND and LNS, respectively, during IDS. Overall survival (OS) was significantly better in the LND group than in the LNS group. In subgroup analysis with negative lymphadenopathy on preoperative imaging, progression-free survival (PFS) and OS were significantly better in the LND group than in the LNS group. Follow-up of subsequent recurrences showed significantly lower nodal and peritoneal recurrence rates among patients who underwent LND. Multivariate analysis identified LND as an independent prognostic factor for PFS and OS. CONCLUSION: Systematic LND may have therapeutic value in advanced EOC patients treated with NAC and IDS.

Long-Term Survival Analysis of Intraperitoneal versus Intravenous Chemotherapy for Primary Ovarian Cancer and Comparison between Carboplatin- and Cisplatin-based Intraperitoneal Chemotherapy.

In epithelial ovarian cancer (EOC), intraperitoneal (IP) administration of chemotherapy is an effective first-line treatment and may improve outcomes, compared with intravenous (IV) chemotherapy. We used Kaplan-Meier survival analysis to compare long-term survival between propensity score-matched patients with advanced EOC receiving IP (n = 34) vs. IV (n = 68) chemotherapy. Additionally, clinical features associated with carboplatin-based (n = 21) and cisplatin-based (n = 16) IP chemotherapy were analyzed and compared with those associated with IV chemotherapy. The IP and IV chemotherapy groups had a median follow-up duration of 67 (range, 3-131) and 62 (range, 0-126) months, respectively, with no significant difference in progression-free survival (PFS) (P = 0.735) and overall survival (OS) (P = 0.776). A significantly higher proportion of patients in the IV (91.2%) than in the IP (67.6%) chemotherapy group (P = 0.004) received ≥ 6 cycles. However, the frequency of toxic events (anemia, granulocytopenia, nausea/vomiting, abdominal pain, hepatotoxicity, neuromuscular effects) was significantly higher in the IP than in the IV group. Within the IP group, no significant differences were observed in PFS (P = 0.533) and OS (P = 0.210) between the cisplatin-based and carboplatin-based chemotherapy subgroups. The 10-year OS was 28.6% and 49.2% in carboplatin-based and cisplatin-based IP chemotherapy groups, respectively. Toxic events (granulocytopenia, leukopenia, nausea/vomiting, abdominal pain, hepatotoxicity, neuromuscular effects) were significantly more common in the cisplatin-based subgroup. In patients with EOC, cisplatin-based IP chemotherapy may be an acceptable alternative to IV chemotherapy regarding long-term survival, but toxicity must be addressed.

Malnutrition Identified by the Nutritional Risk Index and Poor Prognosis in Advanced Epithelial Ovarian Carcinoma.

Ovarian cancer is a chronic disease with a risk of malnutrition. Nutritional Risk Index (NRI) has been reported as a simple and accurate tool to assess the nutritional status. We sought to explore the prevalence of malnutrition and its association with survival in ovarian cancer. A retrospective study was conducted in 213 advanced ovarian cancer patients. NRI was calculated before and at the end of treatment using patients' body weight and serum albumin level. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier method, and associations were assessed using a Cox proportional hazards analysis adjusted for known prognostic variables. Moderate to severely malnourished patients had lower 5-yr OS (45.3%) compared to normal to mild group (64.0%), respectively (P = 0.024). Adjusted for covariates, the relative risk of death was 5.8 times higher in moderate/severely malnourished group identified at the last course of chemotherapy (HR = 5.896, 95% CI = 2.723-12.764, P < 0.001). Similarly, this cohort had shorter PFS compared with normal to mild risk group (median 15 vs. 28 months, P = 0.011). Malnutrition is prevalent among ovarian cancer patients and is found to be a significant predictor for mortality.

Clinical guidelines for ovarian cancer: the Korean Society of Gynecologic Oncology guidelines.

Since the latest practice guidelines for ovarian cancer were developed by the Korean Society of Gynecologic Oncology (KSGO) in 2021, many studies have examined the efficacy and safety of various treatments for epithelial ovarian cancer (EOC). Therefore, the need to develop recommendations for EOC treatments has been raised. This study searched the literature using 4 key items and the Population, Intervention, Comparison, and Outcome: the efficacy and safety of poly-ADP ribose polymerase inhibitors in newly diagnosed advanced EOC; the efficacy and safety of intraperitoneal plus intravenous chemotherapy in optimally debulked advanced EOC; the efficacy and safety of secondary cytoreductive surgery in platinum-sensitive recurrent ovarian cancer; and the efficacy and safety of the addition of bevacizumab to platinum-based chemotherapy in first platinum-sensitive recurrent EOC patients who received prior bevacizumab. The evidence for these recommendations, according to each key question, was evaluated using a systematic review and meta-analysis. The committee of ovarian cancer of the KSGO developed updated guidelines for treatments of EOC.

Clinical Relevance of Uterine Manipulation on Oncologic Outcome in Robot-Assisted versus Open Surgery in the Management of Endometrial Cancer.

In this study, we investigated the impact of uterine manipulation on endometrial cancer survival outcomes. We analyzed patients with endometrial cancer who underwent robot-assisted staging and open staging surgery between 2010 and 2020. Either uterine manipulators or vaginal tubes were utilized in robot-assisted staging. Propensity score matching was performed to correct baseline characteristics. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier curve analysis. In total, 574 patients, including those undergoing robot-assisted staging with a uterine manipulator (n = 213) or vaginal tube (n = 147) and staging laparotomy (n = 214), were analyzed. Propensity score matching was performed for age, histology, and stage as covariates. Before matching, Kaplan-Meier curve analysis showed that PFS and OS were significantly different among the three groups (p < 0.001 and p = 0.009, respectively). In the propensity-matched cohorts of 147 women, the previously suggested differences in PFS and OS were not observed in patients undergoing robot-assisted staging with a uterine manipulator or vaginal tube or open surgery. In conclusion, robotic surgery using a uterine manipulator or vaginal tube did not compromise survival outcomes in endometrial cancer management.

Clinical Relevance of Vaginal Cuff Dehiscence after Minimally Invasive versus Open Hysterectomy.

This study aimed to evaluate the clinical relevance of vaginal cuff dehiscence following a hysterectomy. Data were prospectively collected from all patients who underwent hysterectomies at a tertiary academic medical center between 2014 and 2018. The incidence and clinical factors of vaginal cuff dehiscence after minimally invasive versus open hysterectomy were compared. Vaginal cuff dehiscence occurred in 1.0% (95% confidence interval [95% CI], 0.7-1.3%) of women who underwent either form of hysterectomy. Among those who underwent open (n = 1458), laparoscopic (n = 3191), and robot-assisted (n = 423) hysterectomies, vaginal cuff dehiscence occurred in 15 (1.0%), 33 (1.0%), and 3 (0.7%) cases, respectively. No significant differences in cuff dehiscence occurrence were identified in patients who underwent various modes of hysterectomies. A multivariate logistic regression model was created using the variables indication for surgery and body mass index. Both variables were identified as independent risk factors for vaginal cuff dehiscence (odds ratio [OR]: 2.74; 95% CI, 1.51-4.98 and OR: 2.20; 95% CI, 1.09-4.41, respectively). The incidence of vaginal cuff dehiscence was exceedingly low in patients who underwent various modes of hysterectomies. The risk of cuff dehiscence was predominantly influenced by surgical indications and obesity. Thus, the different modes of hysterectomy do not influence the risk of vaginal cuff dehiscence.

Vaginal Cuff Dehiscence and a Guideline to Determine Treatment Strategy.

In this retrospective study, our aim was to investigate a novel treatment strategy guideline for vaginal cuff dehiscence after hysterectomy based on the mode of operation and time of occurrence in patients who underwent hysterectomy at Severance Hospital between July 2013 and February 2019. We analyzed the characteristics of 53 cases of vaginal cuff dehiscence according to the mode of hysterectomy and time of occurrence. Out of a total of 6530 hysterectomy cases, 53 were identified as vaginal cuff dehiscence (0.81%; 95% confidence interval: 0.4-1.6%). The incidence of dehiscence after minimally invasive hysterectomy was significantly higher in patients with benign diseases, while malignant disease was associated with a higher risk of dehiscence after transabdominal hysterectomy (p = 0.011). The time of occurrence varied significantly based on menopausal status, with dehiscence occurring relatively earlier in pre-menopausal women compared to post-menopausal women (93.1% vs. 33.3%, respectively; p = 0.031). Surgical repair was more frequently required in cases of late-onset vaginal cuff dehiscence (≥8 weeks) compared to those with early-onset dehiscence (95.8% vs. 51.7%, respectively; p < 0.001). Patient-specific factors, such as age, menopausal status, and cause of operation, may influence the timing and severity of vaginal cuff dehiscence and evisceration. Therefore, a guideline may be indicated for the treatment of potentially emergent complications after hysterectomy.