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1.
Obstetrics & Gynecology Science ; : 223-225, 2022.
Article in English | WPRIM | ID: wpr-938917

ABSTRACT

Objective@#To demonstrate near-infrared fluorescence image-guided inguinal sentinel lymph node (SLN) biopsy in patients with vulvar cancer. @*Methods@#A 40-year-old woman with a 3-cm-sized palpable left vulvar mass was diagnosed with vulvar cancer on biopsy with protrusion into the vaginal cavity. Pelvic contrast-enhanced magnetic resonance imaging and F-18 fluorodeoxyglucose positron-emission tomography-computed tomography showed a small ulcerative enhancing lesion confined to the left vulva without distant metastasis. The patient was scheduled for radical vulvectomy with a left inguinal SLN biopsy. Indocyanine green was injected directly into the vulvar mass to map lymphatic drainage. A 4-cm-sized linear incision was made on the left inguinal crease, and the lymphatic channels of the left inguinal area were dissected under fluorescent image guidance using a 1588 Advanced Imaging Modalities Platform laparoscopic camera (Stryker, Kalamazoo, MI, USA). @*Results@#Fluorescence image-guided left inguinal SLN biopsy and radical vulvectomy were performed. The pathologic diagnosis confirmed vulvar adenoid cystic carcinoma with metastasis to the left inguinal lymph node (International Federation of Gynecology and Obstetrics stage IIIA). The patient was discharged without complications and received adjuvant radiotherapy. @*Conclusion@#This video demonstrates a successful ICG fluorescence image-guided left inguinal SLN biopsy in a vulvar cancer patient using a laparoscopic camera. Mapping of inguinal SLNs in patients with vulvar cancer may help in retaining surgical radicality while minimizing operative complications.

2.
Journal of Menopausal Medicine ; : 168-174, 2021.
Article in English | WPRIM | ID: wpr-915701

ABSTRACT

Objectives@#This study compared serum anti-Mullerian hormone (AMH) levels in endometriotic cysts (ECs) with those in non-ECs and analyzed changes thereof after single-port laparoscopic (SPL) ovarian cyst enucleation using vasopressin injection. @*Methods@#In total, 180 patients (EC group, n = 112; non-EC group, n = 68) who underwent SPL ovarian cyst enucleation were retrospectively reviewed. Their AMH levels were checked preoperatively, on postoperative day 10 (POD10), and on postoperative month 3 (POM3). Changes in AMH levels were analyzed according to tumor type and vasopressin use. @*Results@#The median initial and postoperative serum AMH levels in the EC group were significantly lower than those in the nonEC group (preoperation: 2.0 vs 3.8 ng/mL, P < 0.001; POD10: 1.0 vs 3.2 ng/mL, P < 0.001; POM3: 1.2 vs 3.6 ng/mL, P < 0.001). The postoperative decrease in AMH levels was higher in the EC group than the non-EC group on POD10 (0.8 vs 0.5 ng/mL, P = 0.011) but not on POM3 (0.7 vs 0.5 ng/mL, P = 0.164). Vasopressin injection during EC enucleation had no significant effect on the decrease in AMH levels on POD10 (vasopressin group vs non-vasopressin group: 1.0 vs 0.8 ng/mL, P = 0.253) and POM3 (vasopressin group vs nonvasopressin group: 1.4 vs 1.1 ng/mL, P = 0.242). @*Conclusions@#AMH levels were lower at baseline and had higher decreasing rates after SPL surgery in the EC group relative to the nonEC group. Vasopressin injection might not protect the ovary from the postoperative decrease in AMH levels.

3.
Cancer Research and Treatment ; : 549-557, 2021.
Article in English | WPRIM | ID: wpr-897433

ABSTRACT

Purpose@#Population-based comparisons between minimally invasive surgery (MIS) (robotic surgery [RS] and laparoscopic surgery [LS]) and open surgery (OS) for managing endometrial cancer are lacking. This study aimed to compare surgical and oncologic outcomes between endometrial cancer patients who underwent surgical staging via MIS or OS. @*Materials and Methods@#A population-based retrospective cohort study was performed using claims data from the Korean National Health Insurance database from January 2012 to December 2016. All patients who underwent hysterectomy under diagnosis of endometrial cancer were identified. Patients were classified into RS, LS, and OS groups. Operative and oncologic outcomes were compared among the three groups after adjustments for age group, risk group (adjuvant therapy status), modified Charlson comorbidity index, income level, insurance type, and index year using propensity scores obtained via the inverse probability of treatment weighted method. @*Results@#After adjustment, 5,065 patients (RS, n=315; LS, n=3,248; OS, n=1,503) were analyzed. Patient demographics were comparable. Hospital stay, postoperative complications, and cost were more favorable in the RS and LS groups than in the OS group (all p < 0.001). Five-year overall survival was significantly longer in the RS and LS groups than in the OS group (94.8%, 91.9%, and 86.9%, respectively; p < 0.001). Moreover, the survival benefit of RS was shown in the subgroup analysis of low-risk endometrial cancer patients. @*Conclusion@#Our study provides further evidence for the RS being a safe surgical alternative to the LS and OS, especially in low-risk endometrial cancer patients, offering surgical and oncologic outcomes equivalent to other surgical approaches.

4.
Yonsei Medical Journal ; : 68-74, 2021.
Article in English | WPRIM | ID: wpr-875601

ABSTRACT

Purpose@#There is lack of data on direct comparison of survival outcomes between open surgery and robot-assisted staging surgery (RSS) using three robotic arms for endometrial cancer. The purpose of this study was to compare the overall survival (OS) and disease-free survival (DFS) between open surgery and RSS using three robotic arms for endometrial cancer. @*Materials and Methods@#Consecutive women with endometrial cancer who underwent surgery between May 2006 and May 2018 were identified. Robotic procedures were performed using the da Vinci robotic system, and the robotic approach consisted of three robotic arms including a camera arm. Propensity score matching, as well as univariate and multivariate Cox regression of OS and DFS were performed according to clinicopathologic data and surgical method. @*Results@#The study cohort included 423 unselected patients with endometrial cancer, of whom 218 underwent open surgery and 205 underwent RSS using three robotic arms. Propensity score-matched cohorts of 146 women in each surgical group showed no significant differences in survival: 5-year OS of 91% vs. 92% and DFS of 86% vs. 89% in the open and robotic cohorts, respectively (hazard ratio, 1.02; 95% confidence interval, 0.82–1.67). In the univariate analysis with OS as the endpoint, surgical method, age, stage, type II histology, grade, and lymph node metastasis were independently associated with survival. Surgical stage, grade, and type II histology were found to be significant independent predictors for OS in the multivariate analysis. @*Conclusion@#RSS using three robotic arms and laparotomy for endometrial carcinoma had comparable survival outcomes.

5.
Cancer Research and Treatment ; : 243-251, 2021.
Article in English | WPRIM | ID: wpr-874342

ABSTRACT

Purpose@#The objective of this study was to define the learning curve required to attain satisfactory oncologic outcomes of cervical cancer patients who were undergoing open or minimally invasive surgery for radical hysterectomy, and to analyze the correlation between the learning curve and tumor size. @*Materials and Methods@#Cervical cancer patients (stage IA-IIA) who underwent open radical hysterectomy (n=280) or minimal invasive radical hysterectomy (n=282) were retrospectively reviewed. The learning curve was evaluated using cumulative sum of 5-year recurrence rates. Survival outcomes were analyzed based on the operation period (“learning period,” P1 vs. “skilled period,” P2), operation mode, and tumor size. @*Results@#The 5-year disease-free and overall survival rates between open and minimally invasive groups were 91.8% and 89.0% (p=0.098) and 96.1% and 97.2% (p=0.944), respectively. The number of surgeries for learning period was 30 and 60 in open and minimally invasive group, respectively. P2 had better 5-year disease-free survival than P1 after adjusting for risk factors (hazard ratio, 0.392; 95% confidence interval, 0.210 to 0.734; p=0.003). All patients with tumors < 2 cm had similar 5-year disease-free survival regardless of operation mode or learning curve. Minimally invasive group presented lower survival rates than open group when tumors ≥ 2 cm in P2. Preoperative conization improved disease-free survival in patients with tumors ≥ 2 cm, especially in minimally invasive group. @*Conclusion@#Minimally invasive radical hysterectomy required more cases than open group to achieve acceptable 5-year disease-free survival. When tumors ≥ 2 cm, the surgeon’s proficiency affected survival outcomes in both groups.

6.
Obstetrics & Gynecology Science ; : 90-98, 2021.
Article in English | WPRIM | ID: wpr-938863

ABSTRACT

Objectives@#The aims of this study were to assess the feasibility of single-port laparoscopic surgical staging (SPLS) in early ovarian cancer and to compare the surgical outcomes of SPLS with those of staging laparotomy. @*Methods@#Between January 2014 and December 2018, 40 patients underwent SPLS and 41 patients underwent staging laparotomy at Yonsei Cancer Center. The patients were diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage I ovarian cancer. Variables such as patient age, body mass index (BMI), tumor size, FIGO stage, and perioperative surgical outcomes and survival outcomes of SPLS and laparotomy were compared. @*Results@#The total operation time was similar between the 2 groups (SPLS: 201.4 vs. laparotomy: 203.0 minutes, P=0.806). The median tumor diameters in the SPLS and laparotomy groups were 11.0 (2.5–28 cm) and 15.4 (6–40 cm), respectively (P=0.001). The SPLS group had lower tumor spillage rate (5.0% vs. 19.5%, P=0.047), less intraoperative blood loss (102.0 vs. 371.5 mL, P<0.001), less postoperative pain, and shorter postoperative hospital stay (5 vs. 9.5 days, P<0.001). The intraoperative major complication rate was similar between groups (2.5% vs. 4.9%, P=0.571). There was no significant difference in progression-free survival between the 2 groups (P=0.945). There were no deaths in either group. @*Conclusion@#SPLS is feasible in early ovarian cancer and has better perioperative surgical outcomes, in some aspects, than staging laparotomy without compromising survival outcomes. SPLS could be performed in patients suspected to have early ovarian cancer.

7.
Cancer Research and Treatment ; : 549-557, 2021.
Article in English | WPRIM | ID: wpr-889729

ABSTRACT

Purpose@#Population-based comparisons between minimally invasive surgery (MIS) (robotic surgery [RS] and laparoscopic surgery [LS]) and open surgery (OS) for managing endometrial cancer are lacking. This study aimed to compare surgical and oncologic outcomes between endometrial cancer patients who underwent surgical staging via MIS or OS. @*Materials and Methods@#A population-based retrospective cohort study was performed using claims data from the Korean National Health Insurance database from January 2012 to December 2016. All patients who underwent hysterectomy under diagnosis of endometrial cancer were identified. Patients were classified into RS, LS, and OS groups. Operative and oncologic outcomes were compared among the three groups after adjustments for age group, risk group (adjuvant therapy status), modified Charlson comorbidity index, income level, insurance type, and index year using propensity scores obtained via the inverse probability of treatment weighted method. @*Results@#After adjustment, 5,065 patients (RS, n=315; LS, n=3,248; OS, n=1,503) were analyzed. Patient demographics were comparable. Hospital stay, postoperative complications, and cost were more favorable in the RS and LS groups than in the OS group (all p < 0.001). Five-year overall survival was significantly longer in the RS and LS groups than in the OS group (94.8%, 91.9%, and 86.9%, respectively; p < 0.001). Moreover, the survival benefit of RS was shown in the subgroup analysis of low-risk endometrial cancer patients. @*Conclusion@#Our study provides further evidence for the RS being a safe surgical alternative to the LS and OS, especially in low-risk endometrial cancer patients, offering surgical and oncologic outcomes equivalent to other surgical approaches.

8.
Journal of Gynecologic Oncology ; : e23-2020.
Article in English | WPRIM | ID: wpr-834469

ABSTRACT

OBJECTIVE@#To compare the efficacy and toxicity of dose-dense weekly paclitaxel and 3-weekly carboplatin (ddPC) as neoadjuvant chemotherapy (NAC) with the standard 3-weekly regimen.@*METHODS@#A retrospective study of patients diagnosed with stage IIIc and IV ovarian cancer who received at least one cycle of NAC followed by interval debulking surgery between August 2015 and January 2018 was conducted. Patient characteristics, clinical and pathological response to NAC, surgical and survival outcome, and adverse event were compared.@*RESULTS@#A total of 23 patients in the ddPC group and 50 patients in the standard group received a median of 3 cycles of NAC. Rate of grade ≥3 neutropenia was significantly higher in the ddPC group than the standard (82.6% vs. 22.0%, p<0.001). Patients in the ddPC group underwent dose-reduction more frequently (34.8% vs. 4.00%, p=0.001). Normalization of cancer antigen-125 post-NAC occurred more frequently in the ddPC group (73.9% vs. 46.0%, p=0.030). No residual disease rate (43.5% vs. 60.0%, p=0.188) and chemotherapy response score of 3 (34.8% vs. 26.0%, p=0.441) were not statistically different between two groups. There was no statistical difference in progression free survival (PFS) at 2 years (36.3% vs. 28.4%, p=0.454). Cox proportional hazard model showed that ddPC was not a significant determinant of PFS (p=0.816).@*CONCLUSION@#There was no difference between both regimens in terms of NAC response and survival outcomes. However, ddPC group showed higher hematologic toxicity requiring dose reduction.

9.
Cancer Research and Treatment ; : 1211-1218, 2020.
Article | WPRIM | ID: wpr-831148

ABSTRACT

Purpose@#The aim of this study was to evaluate the ability of sequential 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) after one cycle of neoadjuvant chemotherapy (NAC) to predict chemotherapy response before interval debulking surgery (IDS) in advanced-stage ovarian cancer patients. @*Materials and Methods@#Forty consecutive patients underwent 18F-FDG-PET/CT at baseline and after one cycle of NAC. Metabolic responses were assessed by quantitative decrease in the maximum standardized uptake value (SUVmax) with PET/CT. Decreases in SUVmax were compared with cancer antigen 125 (CA-125) level before IDS, response rate by Response Evaluation Criteria in Solid Tumors criteria before IDS, residual tumor at IDS, and I chemotherapy response score (CRS) at IDS. @*Results@#A 40% cut-off for the decrease in SUVmax provided the best performance to predict CRS 3 (compete or near-complete pathologic response), with sensitivity, specificity, and accuracy of 81.8%, 72.4%, and 72.4%, respectively. According to this 40% cut-off, there were 17 (42.5%) metabolic responders (≥ 40%) and 23 (57.5%) metabolic non-responders (< 40%). Metabolic responders had higher rate of CRS 3 (52.9% vs. 8.7%, p=0.003), CA-125 normalization (< 35 U/mL) before IDS (76.5% vs. 39.1%, p=0.019), and no residual tumor at IDS (70.6% vs. 31.8%, p=0.025) compared with metabolic non-responders. There were significant associations with progression-free survival (p=0.021) between metabolic responders and non-responders, but not overall survival (p=0.335). @*Conclusion@#Early assessment with 18F-FDG-PET/CT after one cycle of NAC can be useful to predic response to chemotherapy before IDS in patients with advanced-stage ovarian cancer.

10.
Journal of Gynecologic Oncology ; : 23-2020.
Article in English | WPRIM | ID: wpr-811212

ABSTRACT

OBJECTIVE: To compare the efficacy and toxicity of dose-dense weekly paclitaxel and 3-weekly carboplatin (ddPC) as neoadjuvant chemotherapy (NAC) with the standard 3-weekly regimen.METHODS: A retrospective study of patients diagnosed with stage IIIc and IV ovarian cancer who received at least one cycle of NAC followed by interval debulking surgery between August 2015 and January 2018 was conducted. Patient characteristics, clinical and pathological response to NAC, surgical and survival outcome, and adverse event were compared.RESULTS: A total of 23 patients in the ddPC group and 50 patients in the standard group received a median of 3 cycles of NAC. Rate of grade ≥3 neutropenia was significantly higher in the ddPC group than the standard (82.6% vs. 22.0%, p<0.001). Patients in the ddPC group underwent dose-reduction more frequently (34.8% vs. 4.00%, p=0.001). Normalization of cancer antigen-125 post-NAC occurred more frequently in the ddPC group (73.9% vs. 46.0%, p=0.030). No residual disease rate (43.5% vs. 60.0%, p=0.188) and chemotherapy response score of 3 (34.8% vs. 26.0%, p=0.441) were not statistically different between two groups. There was no statistical difference in progression free survival (PFS) at 2 years (36.3% vs. 28.4%, p=0.454). Cox proportional hazard model showed that ddPC was not a significant determinant of PFS (p=0.816).CONCLUSION: There was no difference between both regimens in terms of NAC response and survival outcomes. However, ddPC group showed higher hematologic toxicity requiring dose reduction.


Subject(s)
Humans , Carboplatin , Disease-Free Survival , Drug Therapy , Neoadjuvant Therapy , Neutropenia , Ovarian Neoplasms , Paclitaxel , Proportional Hazards Models , Retrospective Studies , Treatment Outcome
11.
Yonsei Medical Journal ; : 284-290, 2020.
Article in English | WPRIM | ID: wpr-816707

ABSTRACT

PURPOSE: We evaluated whether adding bevacizumab to current platinum-based chemotherapy could improve clinical outcomes without affecting safety.MATERIALS AND METHODS: We retrospectively reviewed medical records of patients with pathologically confirmed ovarian cancer who received neoadjuvant chemotherapy (NAC) at Yonsei Cancer Hospital. We divided the patients into groups based on the use of bevacizumab for NAC (CP group: carboplatin+paclitaxel vs. BCP group: bevacizumab+carboplatin+paclitaxel) and compared patient characteristics, responses to NAC, and surgical and survival outcomes between the two groups. Overall, 88 patients in the CP group and 16 patients in the BCP group received NAC. The primary endpoint was survival outcomes. Complete resection rate after interval debulking surgery (IDS), cancer antigen 125 (CA-125) normalization after NAC, and chemotherapy response score were secondary endpoints.RESULTS: After NAC treatment, all patients underwent IDS. There were no significant differences in adverse events during NAC or postoperative complications between the two groups (p=0.293 and p=0.485, respectively). There were also no significant differences in CA-125 normalization after NAC (42.0% vs. 43.8%, p=0.899) or complete resection rate after IDS (47.7% vs. 56.3%, p=0.530). However, although the BCP group did not show longer overall survival (OS) (log-rank p=0.854), they had significantly longer progression-free survival (PFS) than the CP group (log-rank p=0.048).CONCLUSION: Bevacizumab-containing NAC might be safe and provide longer PFS than chemotherapy alone in patients with advanced ovarian cancer. However, further study is necessary to investigate the impact of bevacizumab-containing NAC on OS.

12.
Obstetrics & Gynecology Science ; : 538-542, 2020.
Article in English | WPRIM | ID: wpr-902901

ABSTRACT

Malakoplakia is a rare granulomatous, inflammatory disease generally manifesting as ulcers of the urogenital tract, especially in the bladder, but it can occur in any part of the body. Because of its varied clinical presentations, malakoplakia is considered for differential diagnosis upon suspicion. The final diagnosis is confirmed by the presence of Michaelis-Gutmann bodies. We report a case of pelvic malakoplakia accompanied by left lower quadrant pain that was misdiagnosed as endometrial cancer with pelvic mass based on imaging studies. The patient underwent dilatation and curettage, and the pathology report revealed no malignancy. Because of persistent pain and septic shock, she underwent a debulking operation to remove the mass. Histopathologic examination revealed malakoplakia. For postoperative management, she received broad-spectrum antibiotics, but abdominal pelvic computerized tomography performed on postoperative day 9 revealed pelvic mass recurrence. To the best of our knowledge, this is the only rare case report of pelvic malakoplakia mimicking endometrial cancer.

13.
Obstetrics & Gynecology Science ; : 538-542, 2020.
Article in English | WPRIM | ID: wpr-895197

ABSTRACT

Malakoplakia is a rare granulomatous, inflammatory disease generally manifesting as ulcers of the urogenital tract, especially in the bladder, but it can occur in any part of the body. Because of its varied clinical presentations, malakoplakia is considered for differential diagnosis upon suspicion. The final diagnosis is confirmed by the presence of Michaelis-Gutmann bodies. We report a case of pelvic malakoplakia accompanied by left lower quadrant pain that was misdiagnosed as endometrial cancer with pelvic mass based on imaging studies. The patient underwent dilatation and curettage, and the pathology report revealed no malignancy. Because of persistent pain and septic shock, she underwent a debulking operation to remove the mass. Histopathologic examination revealed malakoplakia. For postoperative management, she received broad-spectrum antibiotics, but abdominal pelvic computerized tomography performed on postoperative day 9 revealed pelvic mass recurrence. To the best of our knowledge, this is the only rare case report of pelvic malakoplakia mimicking endometrial cancer.

14.
Journal of Gynecologic Oncology ; : e3-2019.
Article in English | WPRIM | ID: wpr-719307

ABSTRACT

OBJECTIVES: We conducted a protocol-based cohort study to evaluate the outcomes of interval debulking surgery (IDS) followed by paclitaxel-based hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of advanced-stage ovarian cancer. METHODS: From October 2015 to May 2018, 65 patients with stages IIIC–IV ovarian cancer were treated according to the study protocol. HIPEC was performed with paclitaxel (175 mg/m2) for 90 minutes, only in cases of optimal cytoreduction. RESULTS: Of 65 patients, 40 (61.5%) patients underwent neoadjuvant chemotherapy (NAC), 34 (52.3%) patients had a high tumor burden with a Fagotti score ≥8 at diagnostic laparoscopy, and 6 (9.2%) had definite stage IV metastasis and/or poor performance status before NAC. Twenty-seven (41.5%) patients underwent IDS followed by HIPEC. The mean duration of IDS with HIPEC was 543.8 (range, 277.0–915.0) minutes. Grade III/IV perioperative complications occurred in 7.4% (n=2)/3.7% (n=1) of patients and no cases of mortality were reported within 30 days postoperatively. The median progression-free survival was 21.3 months, and the median overall survival was not reached for those who received HIPEC. CONCLUSIONS: According to our study protocol, IDS followed by paclitaxel-based HIPEC as a first-line treatment appears to be feasible and safe for the treatment of advanced-stage ovarian cancer. Further evaluations of this procedure are required to assess its survival benefits.


Subject(s)
Humans , Cohort Studies , Disease-Free Survival , Drug Therapy , Laparoscopy , Mortality , Neoplasm Metastasis , Ovarian Neoplasms , Paclitaxel , Pilot Projects , Tumor Burden
15.
Yonsei Medical Journal ; : 914-923, 2019.
Article in English | WPRIM | ID: wpr-762041

ABSTRACT

PURPOSE: Few efforts have been made to integrate a next generation sequencing (NGS) panel into standard clinical treatment of ovarian cancer. The aim of this study was to investigate the clinical utility of NGS and to identify clinically impactful information beyond targetable alterations. MATERIALS AND METHODS: We conducted a retrospective review of 84 patients with ovarian cancer who underwent NGS between March 1, 2017, and July 31, 2018, at the Yonsei Cancer Hospital. We extracted DNA from formalin-fixed, paraffin-embedded tissue samples of ovarian cancer. The TruSight Tumor 170 gene panel was used to prepare libraries, and the MiSeq instrument was used for NGS. RESULTS: Of the 84 patients, 55 (65.1%) had high-grade serous carcinomas. Seventy-three (86.7%) patients underwent NGS at the time of diagnosis, and 11 (13.3%) underwent NGS upon relapse. The most common genetic alterations were in TP53 (64%), PIK3CA (15%), and BRCA1/2 (13%), arising as single nucleotide variants and indels. MYC amplification (27%) was the most common copy number variation and fusion. Fifty-seven (67.9%) patients had more than one actionable alteration other than TP53. Seven (8.3%) cases received matched-target therapy based on the following sequencing results: BRCA1 or 2 mutation, poly ADP ribose polymerase inhibitor (n=5); PIK3CA mutation, AKT inhibitor (n=1); and MLH1 mutation, PD-1 inhibitor (n=1). Fifty-three (63.0%) patients had a possibility of treatment change, and 8 (9.5%) patients received genetic counseling. CONCLUSION: Implementation of NGS may help in identifying patients who might benefit from targeted treatment therapies and genetic counseling.


Subject(s)
Humans , Cancer Care Facilities , Diagnosis , DNA , Genetic Counseling , Ovarian Neoplasms , Poly(ADP-ribose) Polymerases , Recurrence , Retrospective Studies
16.
Cancer Research and Treatment ; : 1117-1127, 2019.
Article in English | WPRIM | ID: wpr-763168

ABSTRACT

PURPOSE: Recurrence and chemoresistance (CR) are the leading causes of death in patients with high-grade serous carcinoma (HGSC) of the ovary. The aim of this study was to identify genetic changes associated with CR mechanisms using a patient-derived xenograft (PDX) mouse model and genetic sequencing. MATERIALS AND METHODS: To generate a CR HGSC PDX tumor, mice bearing subcutaneously implanted HGSC PDX tumors were treated with paclitaxel and carboplatin. We compared gene expression and mutations between chemosensitive (CS) and CR PDX tumors with whole exome and RNA sequencing and selected candidate genes. Correlations between candidate gene expression and clinicopathological variables were explored using the Cancer Genome Atlas (TCGA) database and the Human Protein Atlas (THPA). RESULTS: Three CR and four CS HGSC PDX tumor models were successfully established. RNA sequencing analysis of the PDX tumors revealed that 146 genes were significantly up-regulated and 54 genes down-regulated in the CR group compared with the CS group. Whole exome sequencing analysis showed 39 mutation sites were identified which only occurred in CR group. Differential expression of SAP25,HLA-DPA1, AKT3, and PIK3R5 genes and mutation of TMEM205 and POLR2A may have important functions in the progression of ovarian cancer chemoresistance. According to TCGA data analysis, patients with high HLA-DPA1 expression were more resistant to initial chemotherapy (p=0.030; odds ratio, 1.845). CONCLUSION: We successfully established CR ovarian cancer PDX mouse models. PDX-based genetic profiling study could be used to select some candidate genes that could be targeted to overcome chemoresistance of ovarian cancer.


Subject(s)
Animals , Female , Humans , Mice , Carboplatin , Cause of Death , Drug Therapy , Exome , Gene Expression , Genome , Heterografts , Odds Ratio , Ovarian Neoplasms , Ovary , Paclitaxel , Recurrence , Sequence Analysis, RNA , Statistics as Topic
17.
Annals of Surgical Treatment and Research ; : 113-118, 2019.
Article in English | WPRIM | ID: wpr-762699

ABSTRACT

PURPOSE: There has been an increasing trend in the use of contralateral prophylactic mastectomy (CPM) among women diagnosed with unilateral breast cancer or mutations in BRCA1 or BRCA2 to reduce the occurrence of contralateral breast cancer. This study aimed to examine trends in the CPM rate according to clinicopathologic and socioeconomic status at a single institution in Korea. METHODS: This study included 128 patients with mutations in BRCA1 or BRCA2. Patients were divided into a CPM group (n = 8) and a non-CPM group (n = 120) between May 2013 and March 2016. The main outcome variables, including epidemiology, clinical features, socioeconomic status, and tumor characteristics, were analyzed. RESULTS: A total of 8 CPMs were performed among 128 patients. All CPM patients were married. The proportion of professional working women was higher in the CPM group (P = 0.049). Most patients who underwent CPM graduated college, compared to less than a third of the non-CPM group (P = 0.013). The CPM group had a higher rate of visits to the Hereditary Breast and Ovarian Cancer (HBOC) clinic (P = 0.021). The risk-reducing salpingo-oophorectomy (RRSO) rate was significantly higher in the CPM group (P < 0.01). CONCLUSION: CPM rates were significantly different according to socioeconomic status. The CPM rate tends to increase in highly educated and professional working women. The socioeconomic status of patients is an important factor in the decision to participate in the HBOC clinic and undergo CPM or RRSO.


Subject(s)
Female , Humans , Breast , Breast Neoplasms , Epidemiology , Korea , Mastectomy , Ovarian Neoplasms , Social Class , Unilateral Breast Neoplasms , Women, Working
18.
Journal of Gynecologic Oncology ; : e63-2018.
Article in English | WPRIM | ID: wpr-716108

ABSTRACT

OBJECTIVE: The choice between primary debulking surgery (PDS) and neoadjuvant chemotherapy (NAC) in advanced ovarian cancer remains controversial. We evaluated NAC use in our center before and after results from a randomized trial were published, with the aim to determine the impact of changes in the neoadjuvant strategy on survival in advanced-stage ovarian cancer. METHODS: We retrospectively investigated the clinical course of 435 patients with ovarian, tubal, or peritoneal carcinoma (International Federation of Gynecology and Obstetrics [FIGO] stage III or IV). According to the period of treatment, we stratified patients into a control group (n=216; diagnosed between 2006 and 2010; 83.8% underwent PDS) and a study group (n=219; diagnosed between 2011 and 2014; 48.9% received NAC followed by interval debulking surgery [IDS]). RESULTS: There were no between-group differences in age, body mass index, histology findings, or tumor grade. Compared to patients in the control group, those in the study group were more likely to receive NAC followed by IDS as first-line treatment (48.9% vs. 16.2%; p < 0.001), cytoreductive surgery to no-residual disease (21.5% vs. 10.2%; p < 0.001), or radical surgery (57.5% vs. 35.6%; p < 0.001). However, there was no between-group difference in postoperative morbidity. Kaplan-Meier analysis showed no between-group differences in progression-free or overall survival (p=0.449 and 0.952, respectively). CONCLUSION: NAC incorporation resulted in increased optimal cytoreduction rates although no significant differences in survival outcomes were noted. NAC is advantageous for patients with high perioperative morbidity or unresectable disease.


Subject(s)
Humans , Body Mass Index , Chemotherapy, Adjuvant , Cytoreduction Surgical Procedures , Drug Therapy , Gynecology , Kaplan-Meier Estimate , Neoadjuvant Therapy , Obstetrics , Ovarian Neoplasms , Retrospective Studies
19.
Cancer Research and Treatment ; : 917-925, 2018.
Article in English | WPRIM | ID: wpr-715966

ABSTRACT

PURPOSE: Next-generation sequencing (NGS) allows simultaneous sequencing of multiple cancer susceptibility genes and may represent a more efficient and less expensive approach than sequential testing. We assessed the frequency of germline mutations in individuals with epithelial ovarian cancer (EOC), using multi-gene panels and NGS. MATERIALS AND METHODS: Patients with EOC (n=117) with/without a family history of breast or ovarian cancer were recruited consecutively, from March 2016 toDecember 2016.GermlineDNAwas sequenced using 35-gene NGS panel, in order to identify mutations. Upon the detection of a genetic alteration using the panel, results were cross-validated using direct sequencing. RESULTS: Thirty-eight patients (32.5%) had 39 pathogenic or likely pathogenic mutations in eight genes, including BRCA1 (n=21), BRCA2 (n=10), BRIP1 (n=1), CHEK2 (n=2), MSH2 (n=1), POLE (n=1), RAD51C (n=2), and RAD51D (n=2). Among 64 patients with a family history of cancer, 27 (42.2%) had 27 pathogenic or likely pathogenic mutations, and six (9.3%) had mutations in genes other than BRCA1/2, such as CHECK2, MSH2, POLE, and RAD51C. Fifty-five patients (47.0%) were identified to carry only variants of uncertain significance. CONCLUSION: Using the multi-gene panel test, we found that, of all patients included in our study, 32.5% had germline cancer-predisposing mutations. NGS was confirmed to substantially improve the detection rates of a wide spectrum of mutations in EOC patients compared with those obtained with the BRCA1/2 testing alone.


Subject(s)
Humans , Breast , Germ-Line Mutation , Ovarian Neoplasms , Prevalence
20.
Cancer Research and Treatment ; : 956-963, 2018.
Article in English | WPRIM | ID: wpr-715962

ABSTRACT

PURPOSE: Although the use of xenograft models is increasing, few studies have compared the clinical features or outcomes of epithelial ovarian cancer (EOC) patients according to the tumorigenicity of engrafted specimens. The purpose of this study was to evaluate whether tumorigenicity was associated with the clinical features and outcomes of EOC patients. MATERIALS AND METHODS: Eighty-eight EOC patients who underwent primary or interval debulking surgery from June 2014 to December 2015 were included. Fresh tumor specimens were implanted subcutaneously on each flank of immunodeficient mice. Patient characteristics, progression-free survival (PFS), and germline mutation spectra were compared according to tumorigenicity. RESULTS: Xenografts were established successfully from 49 of 88 specimens. Tumorigenicity was associated with lymphovascular invasion and there was a propensity to engraft successfully with high-grade tumors. Tumors from patientswho underwent non-optimal (residual disease ≥ 1 cm) primary orinterval debulking surgery had a significantly greater propensity to achieve tumorigenicity than those who received optimal surgery. In addition, patients whose tumors became engrafted seemed to have a shorter PFS and more frequent germline mutations than patients whose tumors failed to engraft. Tumorigenicity was a significant factor for predicting PFS with advanced International Federation of Gynecology and Obstetrics stage and high-grade cancers. CONCLUSION: sTumorigenicity in a xenograft model was a strong prognostic factor and was associated with more aggressive tumors in EOC patients. Xenograft models can be useful as a preclinical tool to predict prognosis and could be applied to further pharmacologic and genomic studies on personalized treatments.


Subject(s)
Animals , Humans , Mice , Disease-Free Survival , Germ-Line Mutation , Gynecology , Heterografts , Obstetrics , Ovarian Neoplasms , Prognosis
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