Risk Factors Affecting Clinical Outcomes of Low-risk Early-stage Human Papillomavirus-Associated Endocervical Adenocarcinoma Treated by Surgery Alone: Application of Silva Pattern.

This study aimed to report the clinical outcomes and risk factors for survival of patients with low-risk early-stage human papillomavirus-associated (HPVA) endocervical adenocarcinoma (EAC) treated with surgery alone. This retrospective study obtained the clinicopathological data of patients with early-stage HPVA EAC who underwent surgery between 2012 and 2018. The Silva pattern of invasion was determined by reviewing pathology slides. Locoregional recurrence-free survival (RFS), RFS, and overall survival were calculated, and the risk factors for survival were analyzed. One hundred seventeen patients with a median follow-up of 5.2 years (0.5-9.7 yr) were included. The most common histologic type was usual (94/117, 80.3%). The Silva pattern was A in 79 patients (67.5%), B in 30 (25.6%), and C in 8 (6.8%). The 5-year locoregional RFS, RFS, and overall survival rates were 92.4%, 87.8%, and 97.2%, respectively. The presence of intermediate-risk factors and Silva pattern C were significantly associated with worse survival. Based on these findings, patients were categorized into 2 groups: Group 1 (Silva pattern A or Silva pattern B without intermediate-risk factors) and Group 2 (Silva pattern B with intermediate-risk factors or Silva pattern C). Group 2 showed significantly worse outcomes than Group 1, including the 5-year locoregional RFS (98.6% vs 68.0%), RFS (96.4% vs 54.6%), and overall survival (100.0% vs 86.5%). In conclusion, surgery alone for early-stage HPVA EAC resulted in favorable outcomes. Consideration of the Silva pattern, in addition to well-known risk factors, could help in precise risk group stratification of low-risk, early-stage HPVA EAC.

Comparison of Minimally Invasive and Open Surgery for the Treatment of Endometrial Cancer with a High Risk of Recurrence: A Propensity Score Matching Study in Korea and Taiwan.

BACKGROUND: This study compared oncologic outcomes between minimally invasive surgery (MIS) and open surgery for the treatment of endometrial cancer with a high risk of recurrence. METHODS: This study included patients with endometrial cancer who underwent primary surgery at two tertiary centers in Korea and Taiwan. Low-grade advanced-stage endometrial cancer (endometrioid grade 1 or 2) or endometrial cancer with aggressive histology (endometrioid grade 3 or non-endometrioid) at any stage was considered to have a high risk of recurrence. We conducted 1:1 propensity score matching between the MIS and open surgery groups to adjust for the baseline characteristics. RESULTS: Of the total of 582 patients, 284 patients were included in analysis after matching. Compared with open surgery, MIS did not show a difference in disease-free survival [hazard ratio (HR) 1.09; 95% confidence interval (CI) 0.67-1.77, P = 0.717] or overall survival (HR 0.67; 95% CI 0.36-1.24, P = 0.198). In the multivariate analysis, non-endometrioid histology, tumor size, tumor cytology, depth of invasion, and lymphovascular space invasion were risk factors for recurrence. There was no association between the surgical approach and either recurrence or mortality in the subgroup analysis according to stage and histology. CONCLUSIONS: MIS did not compromise survival outcomes for patients with endometrial cancer with a high risk of recurrence when compared with open surgery.

Role of salvage radiotherapy for recurrent ovarian cancer.

OBJECTIVE: This study aimed to report clinical outcomes of salvage radiotherapy for recurrent ovarian cancer and identify predictors of clinical outcomes. METHODS: We retrospectively reviewed data of patients who received salvage radiotherapy for recurrent ovarian cancer between January 2011 and June 2021. Stereotactic body radiotherapy, involved-field radiotherapy with conventional fractionation, and non-involved-field radiotherapy with conventional fractionation were included in this study. Local failure-free survival, progression-free survival, chemotherapy-free survival, and overall survival were assessed. Additionally, potential prognostic factors for survival were analyzed. RESULTS: A total of 79 patients were included with 114 recurrent lesions. The median follow-up was 18.3 months (range 1.7-83). The 2-year local failure-free survival, progression-free survival, chemotherapy-free survival, and overall survival rates were 80.7%, 10.6%, 21.2%, and 74.7%, respectively. Pre-radiotherapy platinum resistance (hazard ratio (HR) 3.326, p<0.001) and short pre-radiotherapy CA-125 doubling time (HR 3.664, p<0.001) were associated with poor chemotherapy-free survival. The 1-year chemotherapy-free survival rates of patients with both risk factors, a single risk factor, and no risk factor were 0%, 20.4%, and 53.5%, respectively. The difference between risk groups was statistically significant: low risk versus intermediate risk (p<0.001) and intermediate risk versus high risk (p<0.001). CONCLUSIONS: Salvage radiotherapy for recurrent ovarian cancer resulted in local control with improved chemotherapy-free survival in carefully selected patients. Our results suggest that the consideration of pre-radiotherapy platinum resistance and pre-radiotherapy CA-125 doubling time could help with patient selection.

Impact of no residual disease on postoperative computed tomography on survival in patients with optimally debulked advanced high-grade serous ovarian cancer during upfront surgery.

OBJECTIVE: We sought to investigate the impact of size of residual tumors as determined by postoperative computed tomography (CT) on survival of patients with advanced, high-grade serous ovarian carcinoma (HGSC) who achieved residual disease less than 1 cm after primary debulking surgery (PDS). METHODS: We collected data of patients with stage III HGSC who had residual tumor less than 1 cm after PDS between 2013 and 2018. Surgeon-assessed residual disease during surgery was defined as sR0 (no gross residual) or sR1 (gross residual <1 cm), and radiologist-assessed residual disease on postoperative CT was defined as rR0 (no evidence of disease) or rRany (existing residual disease). All patients were classified into the following groups: sR0/rR0, sR1/rR0, sR0/rRany, and sR1/rRany. RESULTS: A total of 436 patients was placed into the sR0/rR0 (n = 187, 42.9%), sR1/rR0 (n = 59, 13.5%), sR0/rRany (n = 79, 18.1%), or sR1/rRany group (n = 111, 25.5%). Discrepancies between surgical and radiological assessments were recorded for 176 patients (40.4%) including 38 cases of sR1/rRany group with discordant residual tumor location indicated between two methods. During multivariate analysis, patients with ascites on preoperative CT, sR0/rRany group inclusion, and sR1/rRany group inclusion showed unfavorable progression-free and overall survival. CONCLUSIONS: The incorporation of surgical and radiological evaluations for determining the size of residual tumors was more accurate than surgical evaluation only for predicting survival among patients with advanced ovarian cancer who underwent PDS to residual disease less than 1 cm.

Patterns and risk factors of recurrence in low-risk early-stage cervical adenocarcinoma treated with surgery alone: implications on risk group stratification.

OBJECTIVE: Cervical adenocarcinoma has poorer outcomes compared with squamous cell carcinoma; however, treatment is identical irrespective of histologic sub-types. This study aimed to investigate the patterns and risk factors of recurrence following surgery alone for low-risk early-stage cervical adenocarcinoma. METHODS: We retrospectively reviewed patients who underwent surgery alone for low-risk early-stage cervical adenocarcinoma between January 2001 and December 2018 in a single institution. Baseline clinicopathological characteristics were collected to identify the factors associated with recurrence-free survival. RESULTS: A total of 252 patients met the inclusion criteria. Most patients underwent radical hysterectomy (218 patients, 86.5%) and had usual type endocervical adenocarcinoma (190 patients, 75.4%). The International Federation of Gynecology and Obstetrics 2018 stage was IA1 in 72 patients (27.4%), IA2 in 58 (22.1%), IB1 in 51 (19.4%), and IB2 in 71 patients (27.0%). With a median follow-up of 70.4 months (range 6.2-252.5 months), 5-year survival rates were as follows: locoregional recurrence-free survival, 93.0%; recurrence-free survival, 89.6%; overall survival, 94.7%. The recurrence patterns were local in nine patients (32.1%), regional in five patients (17.8%), distant in 10 patients (35.7%), local and distant in one patient (3.6%), regional and distant in two patients (7.2%), and locoregional and distant in one patient (3.6%). In multivariable analysis, negative human papillomavirus (HPV) status (HR 7.314; p<0.001) and deep cervical stromal invasion (HR 5.110; p=0.003) were associated with poor locoregional recurrence-free survival. Patients were stratified based on the number of risk factors and a statistically significant difference in locoregional recurrence-free survival was observed: 5-year survival rates of 99.0%, 84.2%, and 50.0% for patients with 0, 1, and 2 risk factors (0 vs 1, p=0.001; 1 vs 2, p=0.011). CONCLUSION: Surgery alone for low-risk early-stage cervical adenocarcinoma was associated with favorable outcomes over a long follow-up period. Patients with the highest risk of recurrence were those with a negative HPV status and deep cervical stromal invasion. Additional management following surgery may be considered in patients with these risk factors.

Response to Combination Chemotherapy With Paclitaxel/Ifosfamide/Platinum Versus Paclitaxel/Platinum for Patients With Metastatic, Recurrent, or Persistent Carcinoma of the Uterine Cervix: A Retrospective Analysis.

OBJECTIVE: Paclitaxel/ifosfamide/cisplatin triplet has shown a higher response rate than paclitaxel/cisplatin doublet, but the toxicity profile hindered the use of the triplet regimen. In this study, we adjusted the dosage of the triplet regimen and introduced carboplatin in cisplatin-intolerable patients. We tested the efficacy and toxicity of the modified triplet regimen in patients with recurrent or persistent cervical cancer. MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients with recurrent or persistent cervical cancer who were treated between 2003 and 2015 at Samsung Medical Center. Response rate, progression-free survival (PFS), overall survival (OS), and toxicity of paclitaxel/ifosfamide/platinum (TIP) and paclitaxel/platinum (TP) were compared. RESULTS: The overall response rate of TIP was significantly higher than that of TP (52.7% vs 36.4%, P = 0.031). In the TP group, response rate was higher in patients with progression-free interval longer than 12 months (P = 0.028) and those with squamous cell histology (P = 0.028). In TIP group, patients with older than 50 years (P = 0.017), progression-free interval longer than 12 months (P = 0.046), and squamous cell carcinoma histology (P < 0.001) showed higher response rates; but TIP showed higher response on all occasions. Median OS and median PFS were similar for TP and TIP (OS, 22.43 months vs 18.5 months, P = 0.44; PFS, 6.37 months vs 8.3 months, P = 0.48). CONCLUSIONS: Paclitaxel/ifosfamide/platinum showed a higher response rate than TP in patients with recurrent cervical cancer without an increase in severe complications. Considering the high response rate, TIP may be an option for persistent or recurrent cervical cancer.

Minimally invasive compared with open surgery in patients with borderline ovarian tumors.

OBJECTIVE: To compare the surgical and oncological outcomes between laparoscopic (single-port or multi-port) and open surgery in the treatment of patients with borderline ovarian tumors (BOTs). METHODS: A retrospective analysis was performed on 687 patients who underwent single-port laparoscopy (n=89), multi-port laparoscopy (n=223), or open surgery (n=375) due to BOTs. RESULTS: The age, tumor size, tumor marker, and the proportions of radical surgery rate and surgical staging were significantly lower in the single-port laparoscopy and multi-port laparoscopy groups compared with those in the open surgery group (all P<0.001). The operative time, operative blood loss, length of hospital stay, and perioperative complications were also significantly reduced in the two laparoscopic groups compared with those in the open surgery group (all P<0.001). However, there was no significant difference found between the groups with regard to histological type, pathologic stage, and postoperative residual tumor volume. After the median follow-up time of 41.8months, the recurrence-free survival and overall survival rates did not differ between groups. CONCLUSION: Laparoscopy (either the single-port or multi-port) was a preferred alternative to open surgery in the present cohort of BOT patients because it was associated with more favorable surgical outcomes, with no compromise in oncologic outcome.

Preservation of the endometrial enhancement after magnetic resonance imaging-guided high-intensity focused ultrasound ablation of submucosal uterine fibroids.

OBJECTIVE: To evaluate the integrity of endometrial enhancement after magnetic resonance imaging-guided high-intensity focused ultrasound (MR-HIFU) ablation of submucosal uterine fibroids based on contrast-enhanced MRI findings, and to identify the risk factors for endometrial impairment. METHODS: In total, 117 submucosal fibroids (diameter: 5.9 ± 3.0 cm) in 101 women (age: 43.6 ± 4.4 years) treated with MR-HIFU ablation were retrospectively analysed. Endometrial integrity was assessed with contrast-enhanced T1-weighted images at immediate (n = 101), 3-month (n = 62) and 12-month (n = 15) follow-ups. Endometrial impairment was classified into grades 0 (continuous endometrium), 1 (pin-point, full-thickness discontinuity), 2 (between grade 1 and 3), or 3 (full-thickness discontinuity >1 cm). Risk factors were assessed with generalized estimating equation (GEE) analysis. RESULTS: Among 117 fibroids, grades 0, 1, 2 and 3 endometrial impairments were observed at initial examination in 56.4%, 24.8%, 13.7% and 4.3%, respectively. Among 37 fibroid cases of endometrial impairment for which follow-ups were conducted, 30 showed improvements at 3- and/or 12-month follow-up. GEE analysis revealed the degree of endometrial protrusion was significantly associated with severity of endometrial injury (P < 0.0001). CONCLUSIONS: After MR-HIFU ablation of submucosal fibroids, endometrial enhancement was preserved intact or minimally impaired in most cases. Impaired endometrium, which is more common after treating endometrially-protruded fibroids, may recover spontaneously. KEY POINTS: • After MR-HIFU ablation for submucosal fibroid, endometrium is mostly preserved/minimally impaired. • Endometrial-protruded submucosal fibroid is susceptible to more severe endometrial impairment. • The impaired endometrium may recover spontaneously at follow-up MR exams.

Practice Patterns of Hereditary Ovarian Cancer Management in Korea.

OBJECTIVE: This study aims to evaluate practice patterns for managing hereditary ovarian cancer among Korean gynecologic oncologic physicians. METHODS: Members of the Korean Society of Gynecologic Oncology participated in the inaugural Hereditary Gynecologic Cancer Symposium or were invited to this survey by e-mail from January to February 2016. The survey was conducted using a self-administered questionnaire. RESULTS: Most physicians (66.7%, 36/54) responded to draw a pedigree of patients with a family history. The rate of genetic test recommendations for patients at risk for ovarian cancer was high (96.3%, 52/54). Physicians tended to select appropriate candidates for the genetic test. Of the respondents, genetic counseling was commonly performed before the genetic test (76.6%, 36/47) and provided by the specialist consultant(s) (78.7%, 37/47) or the physician alone (12.8%, 6/47). Participants showed mature response to risk management for the BRCA carriers: at least annual gynecologic surveillance (89.4%, 42/47), recommendation for chemoprevention (76.6%, 36/47), and advice for risk-reducing salpingo-oophorectomy (85.1%, 40/47). Risk-reducing salpingectomy with delayed oophorectomy as an alternative to risk-reducing salpingo-oophorectomy was considered to recommend in most of respondents (91.5%, 43/47). CONCLUSIONS: Gynecologic oncologic physicians in Korea had high awareness to genetic risk assessment, candidate selection to genetic test, and risk-reducing strategies for the management of hereditary ovarian cancer.

Opportunistic Salpingectomy Does Not Affect Ovarian Reserve or Surgical Outcomes in Patients Undergoing Laparoscopic Myomectomy.

OBJECTIVE: To determine whether opportunistic salpingectomy in patients undergoing laparoscopic myomectomy has any deleterious effects on ovarian reserve and surgical risk. STUDY DESIGN: We performed a retrospective review of patients who had no desire for future child bearing and who were undergoing laparoscopic myomectomy for symptomatic myomas at 4 institutions. Among them, 41 patients concurrently underwent opportunistic salpingectomy (the opportunistic salpingectomy group) and 65 patients did not undergo salpingectomy at the time of laparoscopic myomectomy (the no-salpingectomy group). The primary and secondary outcome measures were change of ovarian reserve determined by the rate of decline in the anti-Müllerian hormone (AMH) level from before surgery to 3 months post-surgery, and surgical outcomes. RESULTS: Baseline characteristics were similar between groups. There were also no differences in surgical outcomes, such as operative time, operative bleeding, hospital stay, or complications between groups. The decline rate in AMH was 18.6% (interquartile range (IQR) 2.6-46.8%) in the opportunistic salpingectomy group and 10.4% (IQR 2.6-46.8%) in the no-salpingectomy group, with no significant difference between groups (p = 0.593). CONCLUSION: Opportunistic salpingectomy at the time of laparoscopic myomectomy was not associated with negative effects on ovarian reserve or increased surgical risk.

Impact of lymphadenectomy on survival after recurrence in patients with advanced ovarian cancer without suspected lymph node metastasis.

OBJECTIVE: To investigate the impact of pelvic and para-aortic lymphadenectomy during primary debulking surgery (PDS) on recurrence pattern and survival after recurrence in patients with advanced epithelial ovarian cancer (EOC) without suspected lymph node (LN) metastasis in preoperative imaging studies and intraoperative findings. METHODS: A retrospective review of patients with FIGO stage III and IV EOC without suspected lymph node metastasis was performed. Patients with stage III EOC due to LN metastasis without peritoneal disease were excluded from this study. Survival comparisons for progression-free survival (PFS), overall survival (OS), and survival after recurrence were performed between patients with or without lymphadenectomy. RESULTS: Of the 261 EOC patients fulfilling inclusion criteria, 194 (74.3%) experienced relapse and a further 132 (50.6%) died within a median follow-up period of 48months (range, 6-139months). Patterns of recurrence and CA-125 level at recurrence were not different between patients with lymphadenectomy and without lymphadenectomy; however, patients with lymphadenectomy showed longer survival after recurrence than those without lymphadenectomy (43 vs. 32months, p=0.013). This difference was pronounced in the group with residual tumor <1cm (48 vs. 30months, p=0.010). The survival advantage of lymphadenectomy after recurrence remained significant in multivariate analysis (HR 0.57, 95% CI 0.38-0.84, p=0.005). CONCLUSIONS: Lymphadenectomy during PDS was associated with longer survival, especially survival after recurrence. The underlying mechanism should be elucidated in future studies.

Survival impact based on the thoroughness of pelvic lymphadenectomy in intermediate- or high-risk groups of endometrioid-type endometrial cancer: A multi-center retrospective cohort analysis.

OBJECTIVE: To investigate whether the number of lymph nodes obtained during lymphadenectomy affects the survival of patients with intermediate- or high-risk endometrioid-type endometrial cancer. METHODS: A total of 476 patients who were diagnosed with FIGO stage IB to IIIC2 endometrioid adenocarcinoma through surgical staging, including hysterectomy and pelvic lymphadenectomy with or without paraaortic lymphadenectomy between 2000 and 2013 were retrospectively enrolled from four tertiary centers in Korea. Sentinel lymph node mapping was not performed in any patient. The number of nodes obtained and positive nodes, was extracted from pathologic report. RESULTS: Paraaortic lymphadenectomy was performed in 298 (62.6%) patients and 164 (34.4%) had stage IIIC disease. The isolated paraaortic lymph node metastasis rate decreased as the number of pelvic nodes obtained increased. In the total study population, an increase of negative pelvic and paraaortic nodes was associated with improved recurrence-free survival (RFS) and overall survival (OS) independent of other prognostic factors. In the node-positive group, an increase of negative pelvic nodes was an independent prognostic factor for RFS [hazard ratio (HR), 0.946; 95% confidence interval (CI), 0.906-0.988] and OS [HR, 0.907; 95% CI, 0.849-0.968]. In stage IIIC2 patients, 14 or less negative pelvic nodes was associated with poor RFS and OS. CONCLUSIONS: Removing as many pelvic nodes as possible is required to warrant accurate nodal staging and improve survival in patients with intermediate- or high-risk endometrial cancer. Sentinel lymph node mapping can be a resolution to minimize lymph node dissection without compromising staging accuracy.

Long-term Outcomes of MRI Stage IIB Cervical Cancer.

OBJECTIVE: Magnetic resonance imaging (MRI) can be used to assess parametrial invasion (PMI) in cervical cancer. Discordance between MRI findings and International Federation of Gynecology and Obstetrics (FIGO) staging is not uncommon because FIGO staging depends on physical examination. The purpose of this study was to retrospectively evaluate the long-term outcomes of MRI stage IIB cervical cancer. METHODS: A total of 312 patients with MRI stage IIB cervical cancer were retrospectively found between 2002 and 2011. Of these patients, 171 (group 1) were FIGO stage IIB cervical cancers and 141 (group 2) were MRI stage IIB cervical cancers that were negative PMI on physical examination. Group 1 was treated with chemotherapy and/or radiation therapy, and group 2 was treated with radical hysterectomy and lymph node dissection. The FIGO stages and pathologic findings of group 2 were recorded. Groups 1 and 2 were compared regarding 5-year overall survival rate. RESULTS: The FIGO stages of group 2 were IB1 in 51 (36.2%), IB2 in 28 (19.9%), and IIA in 62 (44%), whereas those of group 1 were all IIB. Group 2 showed lymphovascular space invasion in 71 (50.4%), lymph node metastasis in 48 (34.0%), PMI in 46 (32.6%), and vagina invasion in 9 (6.4%). Five-year overall survival rates of groups 1 and 2 were 73.7% and 84.5%, respectively (P = 0.013). CONCLUSIONS: Magnetic resonance imaging stage IIB cervical cancers with negative PMI on physical examination should be surgically treated because of better survival rate than FIGO stage IIB cervical cancers.

Development and Validation of the Korean Version of Hand-Foot Skin Reaction and Quality of Life Questionnaire (HF-QoL-K).

Given the growing number of cancer patients and the resulting increase in the administration of chemotherapeutic agents, convenient and effective methods for measuring the symptoms and quality of life associated with the hand-foot syndrome (HFS) are needed. Therefore, the aim of this study was to develop and validate the Korean version of the hand-foot skin reaction and quality of life questionnaire (HF-QoL-K), comprising a 20-item symptom domain and an 18-item daily activity domain. After we developed the HF-QoL-K, 209 Korean patients with gynecologic cancer who were undergoing chemotherapeutic agents relating the HFS were asked to fill in the questionnaire. The content validity, internal consistency reliability, and test-retest reliability were evaluated. The internal validity index, Cronbach's alpha coefficient, and intra-class correlation coefficient of the HF-QoL-K were 0.90, 0.958, and 0.825 (95% confidence interval [CI], 0.774-0.865), respectively. The scatter plot (Pearson correlation coefficient, 0.826) and the Bland-Altman plot for test-retest reliability were also acceptable. The HF-QoL-K instrument is a valid and reliable questionnaire for the measurement of the symptoms and quality of life in Korean cancer patients suffering HFS.

Clinical outcomes of primary surgical treatment for acquired vulvar lymphangioma circumscriptum.

OBJECTIVE: To assess the clinical outcomes of surgical treatment for acquired vulvar lymphangioma circumscriptum in patients who received radical surgery and/or adjuvant radiation therapy for cervical cancer. METHODS: A retrospective chart review of eight patients was performed to assess the demographic information, chief complaints, treatment modality for cervical cancer, location, and primary treatment modality for vulvar LC, postoperative changes in symptoms, and/or signs, the development of local recurrence and the outcome of patients. RESULTS: All eight patients were previously diagnosed with cervical cancer FIGO clinical stage IA to IIA and received surgery, radiation therapy, or concurrent chemoradiation therapy. Microscopic examination revealed multiple, dilated, D2-40-positive dermal vascular channels containing eosinophilic proteinaceous material, consistent with LC. Most chief complaints showed considerable improvements on assessment at the outpatient clinic after the primary surgery. No patient showed aggravation of symptoms. Two patients developed local recurrences. One patient developed recurrence on the opposite side 13 months after local excision. We performed a second wide local excision. Another patient developed recurrence 47 months after the primary surgery. Since the lesion was very small and localized, we decided to manage it conservatively, but monitor it very closely. The remaining six patients remained free of recurrence. CONCLUSION: It is not easy for gynecologists to have an initial clinical diagnosis of LC, because there are a number of diseases that exhibit similar clinical manifestation to that of vulvar LC. Even if it is diagnosed correctly, local recurrence often occurs. Relevant symptoms associated with LC are not only distressing, but also affect patients' quality of life. Based on our data, we propose that surgical treatment could provide a more long-lasting answer compared to other treatment modalities, since it is beneficial in terms of clinical outcomes. In the future, a long-term follow-up investigation is required to assess the prognosis and to compare the efficacy and side effects of each modality.

Timing and patterns of recurrence in epithelial ovarian cancer patients with no gross residual disease after primary debulking surgery.

OBJECTIVE: The aim of this study was to analyse patterns and timing of recurrence and their association with clinical outcomes in recurrent epithelial ovarian cancer (EOC) patients with no gross residual disease after primary debulking surgery (PDS). METHODS: This study was conducted on 303 EOC patients with no residual disease after PDS who were treated at the Samsung Medical Center from 2002 to 2012. By reviewing electronic medical records, information on date of clinical/pathological recurrence and pattern of disease presentation for each relapse were retrieved. RESULTS: Within a median follow-up of 53 months (range 3-156), 88 recurrences (29.0%) and 28 cancer-related deaths (9.2%) were observed. Most of the recurrences were distant, discrete and transcoelomic. After complete cytoreduction, the initial stage was associated with location of recurrence, but not with recurrence patterns. Complete cytoreduction reduced the number of recurrences, but it did not affect timing of recurrence. In multivariate analysis for overall survival (OS), patients with distant recurrence, diffuse carcinomatosis and mixed spread pattern of transcoelomic, lymphatic and haematogenous recurrence were found to have higher risk. CONCLUSIONS: We found that timing of recurrence was not affected by complete cytoreduction. Location, type and pattern of recurrence were also significant prognostic factors for OS, in addition to known prognostic predictors such as platinum sensitivity.

Sphingosine kinase 1 as a potential therapeutic target in epithelial ovarian cancer.

Sphingosine kinase 1 (SK1) is over-expressed in multiple types of human cancer. SK1 has growth-promoting effects and has been proposed as a potential therapeutic target. We investigated the therapeutic effects of SK1 inhibition in epithelial ovarian carcinoma (EOC). SK1 siRNA or inhibitors were tested in EOC cell lines, including A2780, SKOV3ip1, A2780-CP20, SKOV3-TR, ES2 and RMG2. Cells were treated with SK inhibitor or FTY720, and cell proliferation, apoptosis, angiogenesis and invasion were examined by MTT, FACS, ELISA and wound-healing assays, respectively. In vivo experiments were performed to test the effects of FTY720 on tumor growth in orthotopic mouse xenografts of EOC cell lines A2780 or SKOV3ip1 and a patient-derived xenograft (PDX) model of clear cell ovarian carcinoma (CCC). Blocking SK1 with siRNA or inhibitors significantly reduced proliferation, angiogenesis and invasion, and increased apoptosis in chemosensitive (A2780 and SKOV3ip1) and chemoresistant (A2780-CP20, SKOV3-TR, ES2 and RMG2) EOC cells. SK1 inhibitors also decreased the intracellular enzymatic activity of SK1. Furthermore, FTY720 treatment significantly decreased the in vivo tumor weight in xenograft models of established cell lines (A2780 and SKOV3ip1) and a PDX model for CCC compared to control (p < 0.05). These results support therapeutic targeting of SK1 as a potential new strategy for EOC.

Correlation between location of transposed ovary and function in cervical cancer patients who underwent radical hysterectomy.

OBJECTIVE: The study investigated the association between the location of transposed ovaries and posttreatment ovarian function in patients with early cervical cancer (IB1-IIA) who underwent radical hysterectomy and ovarian transposition with or without adjuvant therapies. METHODS: Retrospective medical records were reviewed to enroll the patients with early cervical cancer who underwent ovarian transposition during radical hysterectomy at Samsung Medical Center between July 1995 and July 2012. Serum follicle-stimulating hormone (FSH) level was used as a surrogate marker for ovarian function. RESULTS: Twenty-one patients were enrolled. The median age and body mass index (BMI) were 31 years (range, 24-39 years) and 21.3 kg/m² (range, 17.7-31.2 kg/m²), respectively. The median serum FSH level after treatment was 7.9 mIU/mL (range, 2.4-143.4 mIU/mL). The median distance from the iliac crest to transposed ovaries on erect plain abdominal x-ray was 0.5 cm (range, -2.7 to 5.2 cm). In multivariate analysis, posttreatment serum FSH levels were significantly associated with the location of transposed ovaries (ß = -8.1, P = 0.032), concurrent chemoradiation (CCRT) as an adjuvant therapy (ß = 71.08, P = 0.006), and BMI before treatment (underweight: ß = -59.93, P = 0.05; overweight: ß = -40.62, P = 0.041). CONCLUSIONS: Location of transposed ovaries, adjuvant CCRT, and BMI before treatment may be associated with ovarian function after treatment. We suggest that ovaries should be transposed as highly as possible during radical hysterectomy to preserve ovarian function in young patients with early cervical cancer who might be a candidate for adjuvant CCRT and who have low BMI before treatment.

Perioperative Outcomes of Radical Trachelectomy in Early-Stage Cervical Cancer: Vaginal Versus Laparoscopic Approaches.

OBJECTIVE: This study aimed to compare the laparoscopic-assisted radical vaginal trachelectomy (LARVT) and laparoscopic radical trachelectomy (LRT) surgical approaches and provide outcome data on patients who have undergone radical trachelectomy. METHODS: We identified patients who had undergone LARVT or LRT at Samsung Medical Center between January 2005 and March 2013. RESULTS: A total of 38 patients were identified, and 21 patients had undergone LARVT, whereas 17 patients had undergone LRT. The median age was 32 years for both groups. Most of the patients had a squamous cell carcinoma (68.4%) and International Federation of Gynecology and Obstetrics stage IB1 disease (76.3%). Twenty (52.6%) of 38 patients had tumor size greater than 2 cm. There were no significant differences between groups in the baseline characteristics except for the tumor size. Patients undergoing LRT had significantly larger tumor size than patients undergoing LARVT (median tumor size, 2.7 cm [range, 1.2-3.7] vs 2.1 cm [range, 0.4-3.0], P = 0.032). Perioperative outcomes were similar between groups except for the decline of hemoglobin after surgery. The median decline of hemoglobin indicating blood loss was significantly smaller in the LRT group than in the LARVT group (1.8 g/dL [range, 0.5-3.5] vs 2.6 g/dL [range, 0.7-6.2], P = 0.017). Intraoperative complications occurred in 2 patients (9.5%, 2/21) in LARVT group. Although 52.6% of tumors were larger than 2 cm, recurrence occurred only in 3 (7.9%) patients who underwent LARVT. CONCLUSIONS: The study shows the feasibility of LRT, with the advantage of reduced blood loss. The LRT could be an alternative option for patients with large tumors. Further researches are needed to investigate the long-term outcomes.