Endometriosis-Related Chronic Pelvic Pain.

Endometriosis, which is the presence of endometrial stroma and glands outside the uterus, is one of the most frequently diagnosed gynecologic diseases in reproductive women. Patients with endometriosis suffer from various pain symptoms such as dysmenorrhea, dyspareunia, and chronic pelvic pain. The pathophysiology for chronic pain in patients with endometriosis has not been fully understood. Altered inflammatory responses have been shown to contribute to pain symptoms. Increased secretion of cytokines, angiogenic factors, and nerve growth factors has been suggested to increase pain. Also, altered distribution of nerve fibers may also contribute to chronic pain. Aside from local contributing factors, sensitization of the nervous system is also important in understanding persistent pain in endometriosis. Peripheral sensitization as well as central sensitization have been identified in patients with endometriosis. These sensitizations of the nervous system can also explain increased incidence of comorbidities related to pain such as irritable bowel disease, bladder pain syndrome, and vulvodynia in patients with endometriosis. In conclusion, there are various possible mechanisms behind pain in patients with endometriosis, and understanding these mechanisms can help clinicians understand the nature of the pain symptoms and decide on treatments for endometriosis-related pain symptoms.

A predictive model based on site-specific risk factors of recurrence regions in endometrial cancer patients.

OBJECTIVE: This study investigated site-specific differences in clinical factors for recurrence in patients who were newly diagnosed and treated for endometrial cancer. A model for predicting recurrence sites was generated. METHODS: Electronic medical records' data were retrieved from January 2006 to December 2018 for patients who were diagnosed with endometrial cancer at the National cancer center in Korea. Recurrence sites were classified as local, regional, or distant. We used multinomial logistic regression models that modeled the log-odds for the three recurrence sites relative to non-recurrence as a linear combination of possible risk factors for the recurrence of endometrial cancer. RESULTS: The data of 611 patients were selected for analysis; there were 20, 12, and 25 cases of local, regional, and distant recurrence, respectively, and 554 patients had no recurrence. High-grade disease was associated with local recurrence; non-endometrioid histology and parametrial invasion were risk factors for regional recurrence; additionally, parametrial invasion and no lymphadenectomy were associated with distant metastasis. CONCLUSION: We identified different risk factors specific for each type of recurrence site. Using these risk factors, we suggest that individually tailored adjuvant treatments be introduced for patients.

Clinical implications of neoadjuvant chemotherapy in advanced endometrial cancer: a multi-center retrospective cohort study.

BACKGROUND: The mainstay of endometrial cancer treatment is surgical resection of tumors and postoperative adjuvant treatment is recommended if necessary. However, there is no consensus on the management of unresectable metastatic endometrial cancer. This study aimed to assess the feasibility and effectiveness of neoadjuvant chemotherapy followed by interval debulking surgery (NAC-IDS) in unresectable, metastatic endometrial cancer. METHODS: From the endometrial cancer cohorts of four institutions in Korea, we identified patients with International Federation of Gynecology and Obstetrics stages IIIC-IVB endometrial cancer who received NAC-IDS between January 2008 and December 2020. Through a medical record review, we collected patients' clinicopathological data. Progression-free survival (PFS), overall survival (OS), and the factors affecting survival outcomes were analyzed. RESULTS: Overall, 32 patients were included with endometrioid (n = 18), serous (n = 5), carcinosarcoma (n = 6), and other histological types (n = 3). Among them, 28 (87.5%) patients had stage IVB disease. The most common neoadjuvant chemotherapy (NAC) regimen was paclitaxel-carboplatin (n = 25, 78.1%), which was administered for a median of six cycles. While 26 (81.3%) patients showed an objective response, two (6.3%) progressed despite NAC. At the time of interval debulking surgery (IDS), 23 (71.9%) patients achieved complete cytoreduction. During 31.0 months of the median follow-up, there were 23 recurrences and 11 deaths, corresponding to a median PFS of 19.7 months and a 3-year OS rate of 69.7%. In multivariate analyses, non-endometrioid histology and residual tumor after IDS were identified as independent poor prognostic factors for PFS (adjusted hazard ratio [HR], 7.322; P < 0.001 and 5.934; P = 0.001, respectively). Multivariate analysis for OS could not be conducted because of the small number of events, although non-endometrioid histology was the only factor associated with worse OS in univariate analysis (adjusted HR, 4.523; P = 0.032). CONCLUSIONS: NAC-IDS may be a treatment option for unresectable metastatic endometrial cancer. Tumor histology and the possibility of complete cytoreduction are the primary considerations for NAC-IDS.

Predicting the risk of the distant recurrence of cervical cancer after concurrent chemoradiation: A validation study of the Korean Gynecologic Oncologic Group (KGOG)-1024 model.

BACKGROUND: This study aimed to validate the performance of the Korean Gynecologic Oncologic Group (KGOG)-1024 risk model in predicting the risk of distant failure after chemoradiation in patients with locally advanced cervical cancer (LACC). METHODS: In a retrospective cohort of 297 patients who received concurrent chemoradiation for advanced cervical cancer, individual risk was calculated using the KGOG-1024 risk model. The cohort was categorized into three risk groups (low-, intermediate-, and high-risk groups) according to the calculated risk. The means of the calculated and observed risks were compared within each group. RESULTS: The study population was classified into low-, intermediate-, and high-risk groups according to the KGOG-1024 risk model (27.2%, 49.3%, and 23.5% of patients, respectively). The calculated and observed 5-year cumulative incidence rates were 12.4% vs. 16.4% in the low-risk group, 23.2% vs. 25.9% in the intermediate-risk group, and 50.7% vs. 36.3% in the high-risk group. Overall, the calculated and observed risk was 26.7% vs. 25.6%. CONCLUSIONS: The KGOG-1024 risk assessment model accurately predicted distant recurrence after chemoradiation in patients with LACC, especially in the low- and intermediate-risk groups. The model may be helpful for identifying patients for future trials assessing the possible benefit of adjuvant systemic treatment after chemoradiation.

Real-world Experience of Niraparib in Newly-diagnosed Epithelial Ovarian Cancer.

BACKGROUND/AIM: Niraparib is effective against epithelial ovarian cancer (EOC), but with adverse effects. In this study, we retrospectively investigated niraparib maintenance treatment feasibility in Korean patients newly diagnosed with EOC. PATIENTS AND METHODS: The medical records of 35 patients were reviewed. Data on the baseline clinical characteristics were collected, and adverse effects were described. RESULTS: Sixteen patients underwent treatment suspension or dose reduction. There was no significant difference in adverse effects (A/E) due to the interval between adjuvant chemotherapy conclusion and niraparib initiation. The two groups had similar International Federation of Gynaecology and Obstetrics (FIGO) stages. The number of patients with a history of bevacizumab use was higher in the dose modification group than in the standard dose group. CONCLUSION: Niraparib use must be considered in those previously treated with bevacizumab. There is a need for prospective research on lower dose (<200 mg) treatments in patients with risk factors.

How to manage synchronous endometrial and ovarian cancer patients?

BACKGROUNDS: We aimed to evaluate the prognosis in patients with synchronous endometrial and ovarian cancer (SEOC) by comparing the differences between double primary cancer (DPC) and metastatic cancer (MC). METHODS: The medical records of 47 patients diagnosed synchronously with endometrial and ovarian cancer between January 2006 and December 2018 were retrospectively reviewed. Twenty-eight and 19 patients were diagnosed with DPC and MC, respectively. Demographics, recurrence-free survival (RFS), and 5-year overall survival (OS) were compared. The clinical factors affecting survival were evaluated using univariate and multivariate analyses. RESULTS: The demographics were not different between both groups. Endometrioid histology and the International Federation of Gynecology and Obstetrics grade were higher in the MC group than in the DPC group (42.1% vs. 10.7%; P = 0.018, P = 0.002, respectively). The ratio of post-operative adjuvant therapy was not different in both groups. Recurrence occurred in five patients with DPC and seven with MC. The difference in RFS was not significantly different (P = 0.131) but the OS was different between both groups (P = 0.020). Histology and para-aortic lymph node metastasis were associated wtih RFS in univariate analysis, but no difference was found in multivariate analysis. CONCLUSIONS: Although DPC patients had longer OS, multivariate analysis did not identify any influential factors. Focus should be placed on defining the appropriate adjuvant treatment for high-risk patients, which will improve prognosis, rather than on discriminating between DPC and MC.

Narrative review of liver mobilization, diaphragm peritonectomy, full-thickness diaphragm resection, and reconstruction.

Epithelial ovarian cancer is the most lethal among gynecologic cancers. Despite advances in research efforts to cure this disease, the recurrence and survival rates have not significantly improved. Primary cytoreductive surgery and adjuvant chemotherapy are the standard treatment options for patients with epithelial ovarian cancer. Two randomized trials recently introduced neoadjuvant chemotherapy followed by interval cytoreductive surgery as an alternative treatment option. In any case, the size of the residual tumor after surgery is the most important prognostic factor for patients with ovarian cancer. With the improvement of surgical techniques in gynecologic oncology, cytoreductive surgery is now performed for the pelvic area and entire abdomen. Currently, surgical resectability of a mass spreading into the upper abdomen is the most important factor for achieving optimal cytoreduction. In this study, we explain the procedure of a cytoreductive surgery, involving the resection of a tumor located in the upper abdomen. We aimed to review and describe the surgical techniques involved in liver mobilization, diaphragm peritonectomy, and full-thickness diaphragm resection and reconstruction. Further, we have assessed the postoperative care involved and discussed complications that may possibly arise along with suggestions to avoid them based on the review of previous literature on the subject.

Comparing survival outcomes for cervical cancer based on the 2014 and 2018 International Federation of Gynecology and Obstetrics staging systems.

The International Federation of Gynecology and Obstetrics (FIGO) cervical cancer staging system was modified in 2018, introducing new stage IB subdivisions and new lymph node status considerations in stage IIIC. We compared cervical cancer survival outcomes according to the 2014 and 2018 FIGO staging systems. We selected 10% of cervical cancer cases (2010-2015) from the Korean national cancer registry (2010-2015) through a systematic sampling method. We collected information using a collaborative stage data collection system and evaluated the results according to both staging systems. The log-rank test was used to analyze overall survival differences. No significant difference in survival was observed between 2018 subdivisions IB1/IB2/IB3 (P = 0.069), whereas a considerable difference was observed between these subdivisions according to histological subtypes. In the 2018 FIGO staging system, stage IIIC had better survival than stage IIIA/IIIB (P < 0.001). We observed considerable heterogeneity in 2018 stage IIIC related to the corresponding stages of the 2014 staging system (stages IA1-IIIB). The size of the primary cervical mass was related to survival (P < 0.001). In conclusion, using lymph node status to define stage IIIC captured a broad range of prognoses. The inclusion of primary tumor size considerations may improve the staging accuracy of advanced cervical cancer.

The Knowledge and Attitude of Patients Diagnosed with Epithelial Ovarian Cancer towards Genetic Testing.

This study assessed the knowledge and attitude of patients with ovarian cancer (OC) toward OC and next generation sequencing (NGS). The data, including characteristics of patients, their knowledge about OC and their knowledge and attitude of NGS, were collected from June to October 2018. Of the 103 participants, 70.9% (n = 73) had cancer within the second-degree relatives, and 18.4% (n = 19) had BRCA pathogenic mutations. The percentage of right answer for the knowledge about OC and NGS was 64.7% (11/17) and 50% (6/12), respectively. The median number of patients who had positive expectations for the genetic test was 34 (range, 22-44). Based on a first-degree familial history, patients had a different degree of knowledge about OC (11 vs. 8.5, p = 0.026) and NGS (6.5 vs. 5, p = 0.011), but patients with a BRCA pathogenic mutation did not have a different degree of knowledge about OC and NGS panel testing. High-income families had a more positive attitude towards the genetic test than low-income families (p = 0.005). Women with OC do not have enough knowledge about OC (11/17, 64.7%) and NGS (6/12, 50%) but they showed a positive attitude toward the NGS test. These women need OC and NGS educational intervention.

Incidence of venous thromboembolism after standard treatment in patients with epithelial ovarian cancer in Korea.

BACKGROUND: Venous thromboembolism (VTE) is a hospital-associated severe complication that may adversely affect patient prognosis. In this study, we evaluated the incidence of VTE and its risk factors in patients with epithelial ovarian cancer (EOC). METHODS: We retrospectively analyzed the electronic health record data of 1268 patients with EOC who received primary treatment at the National Cancer Center, Korea between January 2007 and December 2017 to identify patients who developed VTE. Demographic, clinical, and surgical characteristics of these patients were ascertained. Competing risks analyses were performed to estimate the cumulative incidence of VTE according to the treatment type. The associations between putative risk factors and the incidence of VTE were evaluated using the Fine-Gray regression models accounting for competing risks of death. RESULTS: VTE was the most prevalent cardiovascular event, found in 9.6% (n = 122) of all patients. Of these VTE events, 115 (94.3%) occurred within 2 years of EOC diagnosis. Advanced cancer stage at diagnosis (distant vs. localized, hazards ratio [HR])= 14.49, p = 0.015) and extended hospital stay (≥15 days, HR =3.87, p = 0.004) were associated with the incidence of VTE. There was no significant difference in the cumulative incidence of VTE between primary cytoreductive surgery followed by adjuvant chemotherapy and neoadjuvant chemotherapy followed by interval cytoreductive surgery (HR =0.81, p = 0.390). CONCLUSIONS: Approximately 10% of patients with EOC were diagnosed with VTE, which was the most common cardiovascular disease found in this study. The assessment of VTE risks in patients with advanced-stage EOC with an extended hospital stay is needed to facilitate adequate prophylactic treatment.

Uptake of Family-Specific Mutation Genetic Testing Among Relatives of Patients with Ovarian Cancer with BRCA1 or BRCA2 Mutation.

PURPOSE: The BRCA1 or BRCA2 gene is transmitted in an autosomal dominant fashion, and genetic testing of first-degree relatives of patients with family-specific mutation (FSM) is recommended. This study examined factors affecting the uptake of FSM testing among relatives of patients with peritoneal, ovarian, or fallopian tube (POFT) cancer with confirmed BRCA1 or BRCA2 germline mutation. MATERIALS AND METHODS: Data from medical charts of 392 eligible patients and their relatives who had undergone outpatient genetic counseling/testing were retrospectively reviewed. Clinical factors were compared between family members who had and had not undergone genetic counseling/testing. RESULTS: The uptake of FSM testing was 30.5% (129/423) among first-degree living relatives and 53.5% (69/129) within the overall family unit. The average time from genetic testing of the proband to the first FSM test within a family was 168 days (range, 23 to 681 days). Having a living father (33.8% vs. 13.3%, p=0.007) and daughter (79.4% vs. 60.3%, p=0.019) increased the uptake of FSM testing. FSM testing was more likely among female than among male relatives of cancer patients (40.9% vs. 17.6%, p < 0.001). CONCLUSION: Approximately one-third of first-degree relatives of patients with a POFT cancer with BRCA1 or BRCA2 mutation underwent FSM testing. Having a living father or daughter was a factor affecting the uptake of FSM testing, which was higher among female than among male relatives of the proband. This discrepancy might be due to a misconception that the BRCA gene is associated with women rather than with men.

Survival Effects of Cytoreductive Surgery for Refractory Patients after Neoadjuvant Chemotherapy in Advanced Epithelial Ovarian Cancer.

PURPOSE: Salvage second-line chemotherapy is usually recommended for patients with advanced epithelial ovarian cancer (AEOC) who develop progressive disease (PD) after neoadjuvant chemotherapy (NAC). Herein, we investigated the role of cytoreductive surgery (CRS) for such patients. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 36 patients with AEOC who developed PD after receiving NAC at two tertiary academic centers with different treatment strategies between 2001 and 2016. Patients who developed PD after NAC were consistently treated with CRS at one hospital (group A; n=13) and second-line chemotherapy at another (group B; n=23). The clinical characteristics and treatment outcomes were compared between the groups. RESULTS: Overall survival (OS) was longer in group A than in group B (19.4 months vs. 7.9 months; p=0.011). High-grade serous histology was associated with longer OS than non-high-grade serous types. In group A, optimal surgery resection (<1 cm) was achieved after CRS in 6 patients (46%). Multivariate analysis showed that the treatment option was the only independent predictive factor for OS (hazard ratio, 2.30; 95% confidence interval, 1.02-5.17; p=0.044). CONCLUSION: CRS may result in a survival benefit even in patients with AEOC who develop PD after NAC.

The survival effect of ovary preservation in early stage endometrial cancer: a single institution retrospective analysis.

PURPOSE: We investigated the effect of ovary preserving surgery in early International Federation of Obstetrics and Gynecology (FIGO) stage endometrial cancer patients. METHODS: Medical records were retrospectively reviewed for 539 patients who were diagnosed with early stage endometrial cancer between Jan 2006 and Dec 2017. Patients were categorized into ovary preservation and ovary removal groups. Demographics, recurrence free survival (RFS), and five-year overall survival (OS) rate were compared, and the clinical factors affecting survival were evaluated by univariate and multivariate analysis. RESULTS: The median follow-up period was 85 months (range, 6-142 months), and the median age was 52.7 years. The mean age was higher in the ovary removal group than in the ovary preservation group (54.4 vs 40.94 years; P < 0.001). The ovary preservation group showed an earlier FIGO stage than the ovary removal group (P = 0.0264). There was a greater incidence of adjuvant chemotherapy administration in the removal group. There were no statistical differences in other baseline characteristics. When comparing the RFS and OS rates, there were no statistical differences between the preservation and removal groups. (recurrence free rate 98.5% vs 92.7%, p = 0.4360, and 5-year survival rate 98.6% vs 93.0%, p = 0.0892, respectively). Endometrioid histology (p = 0.006) and post-operative adjuvant chemotherapy (p = 0.0062) were related to OS, and adjuvant chemotherapy (p < 0.001) and radiotherapy (p = 0.005) were related to RFS. CONCLUSIONS: Ovary preservation in early stage endometrial cancer is worth considering, as it does not affect survival in early stage endometrial cancer patients.

Incidence trends for epithelial peritoneal, ovarian, and fallopian tube cancer during 1999-2016: a retrospective study based on the Korean National Cancer Incidence Database.

OBJECTIVE: Primary peritoneal cancer (PPC), ovarian cancer (OC), and fallopian tube cancer (FTC) are considered as a single disease group. As knowledge of the pathogenesis and clinical presentation of peritoneal, ovarian, and fallopian tube (POFT) cancer grows, the tendencies in OC diagnosis are changing. We investigate the incidence and clinical characteristics of epithelial POFT based on cancer site and histologic type. METHODS: Data from the Korea Central Cancer Registry for the period between 1999 and 2016 were analyzed. The incidence rates and annual percent changes (APCs) for each tumor site were reported. RESULTS: Among 27,768 women with cancer, 1,086 (3.91%) had PPC, 25,847 (93.08%) had OC, and 835 (3.01%) had FTC. Age-standardized rates increased from 0.05 to 0.24, 3.51 to 5.48, and 0.04 to 0.28 in PPC, OC, and FTC, respectively. The proportion of PPC and FTC among all the POFT cases increased consistently during the study period (from, respectively, 1.48 and 1.06 in 1999 to 4.52 and 4.76 in 2016). The APC of PPC, OC, and FTC during 1999-2016 was 9.3%, 2.7%, and 8.6%, respectively. The incidence of PPC, OC, and FTC was highest among patients in the 65-69, 50-54, and 55-59 years age group, respectively. CONCLUSION: The overall incidence of PPC, OC, and FTC cancer has steadily increased. The relative increase of PPC and FTC has been significant. In this study, OC incidence had a relatively young peak age, in contrast to FTC and PPC, which had an older peak age.

Real-World Experience of Olaparib Maintenance in High-Grade Serous Recurrent Ovarian Cancer Patients with BRCA1/2 Mutation: A Korean Multicenter Study.

BACKGROUND: Olaparib maintenance therapy has shown efficacy and tolerability in patients with platinum-sensitive, high-grade serous recurrent ovarian cancer (HSROC) with BRCA1/2 mutation (BRCAm). Our aim was to present real-world experience with olaparib in Korea. METHOD: We included HSROC patients with BRCAm treated with olaparib maintenance at four institutions in Korea between 2016 and 2018. Medical records were reviewed for clinico-pathologic characteristics, objective response, survival outcomes, and safety. RESULTS: One hundred HSROC patients with BRCAm were included. BRCA1 mutation was present in 71 patients (71.0%), and BRCA2 mutation was present in 23 patients (23.0%). In terms of the best objective response with olaparib maintenance in 53 patients with partial remission from most recent chemotherapy, complete remission occurred in 12 (22.6%) and partial remission in four (7.5%), while 33 patients (62.3%) had stable disease. The 24 month progression-free survival was 42.4%, and 24 month overall survival was 82.1%. Grade 3 or more adverse events were as follows: anemia in 14 patients (14.0%), neutropenia in seven patients (7.0%), thrombocytopenia in two patients (2.0%), oral mucositis in one patient (1.0%), and soft tissue infection in one patient (1.0%). CONCLUSIONS: The safety and effectiveness of olaparib maintenance treatment in a real-world study were consistent with those reported in previous clinical trials.

Clinical characteristics and outcomes of placental site trophoblastic tumor: experience of single institution in Korea.

OBJECTIVE: Placental site trophoblastic tumor (PSTT) is the rarest form of gestational trophoblastic disease (GTD) and the optimum management is still controversial. In this study, we analyzed the clinical features, treatment, and outcomes of 6 consecutive patients with PSTT treated in our institution. METHODS: The electronic medical record database of Samsung Medical Center was screened to identify patients with PSTT from 1994 to 2017. Medical records for the details of each patient's clinical features and treatment were extracted and reviewed. This study was approved Institutional Review Board of our hospital. RESULTS: A total of 418 cases of GTD, 6 (1.4%) patients with PSTT were identified. The median age of the patients was 31 years. The antecedent pregnancy was term in all 5 cases with available antecedent pregnancy information and the median interval from pregnancy to diagnosis of PSTT was 8 months. The median titer of serum beta human chorionic gonadotropin (ß-hCG) at diagnosis was 190.9 mIU/mL. Five (83.3%) patients presented with irregular vaginal bleeding and one (16.7%) had amenorrhea. All patients had disease confined to the uterus without metastasis at diagnosis and were successfully treated by hysterectomy alone. All of them were alive without disease during the follow-up period. CONCLUSION: In this study, we observed low level serum ß-hCG titer and irregular vaginal bleeding with varying interval after antecedent term pregnancy were most common presenting features of PSTT. In addition, we demonstrated hysterectomy alone was successful for the treatment of stage I disease of PSTT.

Retrospective study of combination chemotherapy with etoposide and ifosfamide in patients with heavily pretreated recurrent or persistent epithelial ovarian cancer.

OBJECTIVE: This retrospective study is to evaluate the efficacy and toxicity of combination chemotherapy with etoposide and ifosfamide (ETI) in the management of pretreated recurrent or persistent epithelial ovarian cancer (EOC). METHODS: Patients with recurrent or persistent EOC who had measurable disease and at least one chemotherapy regimen were to receive etoposide at a dose of 100 mg/m2/day intravenous (IV) on days 1 to 3 in combination with ifosfamide 1 g/m2/day IV on days 1 to 5, every 21 days. RESULTS: From August 2008 to August 2016, 66 patients were treated with ETI regimen. Most patients were heavily pretreated prior to ETI: 53 (80.3%) patients had received 3 or more chemotherapy regimens. The response rate (RR) of ETI chemotherapy was 18.2% and median duration of response was 6.8 months (range, 0-30). Median survival of all patients was 5 months at a median follow up of 7.2 months. Platinum-free interval (PFI) more than 6 months prior to ETI has statistically significant correlation with overall survival (OS; 9.2 vs. 5.6 months; P=0.029) and RR (34.5% vs. 5.4%; P<0.010). However, treatment free interval before ETI, number of prior chemotherapy regimen, and optimality of primary surgery did not show significant difference for RR or OS. Grade 3 or 4 hematologic toxicities were observed in 7 cases (3%) of the 232 cycles of ETI. CONCLUSION: The ETI combination regimen shows comparatively low toxicity and modest activity in heavily pretreated recurrent or persistent EOC patients with more than 6 months of PFI after last platinum treatment.