Publications by authors named "Koji Matsuo"

415 Publications

Population-level trends and outcomes of sentinel lymph node biopsy in vulvar cancer surgery in the United States.

Gynecol Oncol 2022 Jan 11. Epub 2022 Jan 11.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA. Electronic address:

Objective: To examine population-level trends, characteristics, and outcomes related to nodal assessment for vulvar cancer surgery in the United States.

Methods: This is a retrospective cohort study querying the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. The study population was 5604 women with T1b or T2-smaller(≤4 cm) squamous cell carcinoma of the vulva who underwent primary vulvectomy from 2003 to 2018. The exposure allocation was based on nodal evaluation type: lymphadenectomy (LND; n = 3319, 59.2%), sentinel lymph node (SLN) biopsy (n = 751, 13.4%), or no surgical nodal evaluation (n = 1534, 27.4%). The main outcomes were (i) trends and characteristics related to SLN biopsy assessed by multinomial regression model, and (ii) vulvar cancer-specific survival assessed by competing risk analysis and inverse probability of treatment weighting propensity score. Sensitivity analysis included evaluation of external cohort with T1a disease (n = 1291).

Results: The utilization of SLN biopsy increased from 5.7% to 23.3% in 2006-2018, while the proportion of LND decreased from 64.1% to 48.8% in 2010-2018, and these associations remained independent in multivariable analysis (adjusted-P < 0.05). In the propensity score weighted model, 5-year cumulative rate for vulvar cancer-specific mortality was 15.2% (interquartile range 12.1-18.9) for the SLN biopsy group and 16.9% (interquartile range 15.6-18.3) for the LND group (subdistribution-hazard ratio 0.90, 95% confidence interval 0.76-1.06, P = 0.217). The increasing SLN biopsy use was also observed in T1a disease from 1.3% to 7.3% during the study period (P < 0.001).

Conclusion: The landscape of surgical nodal evaluation is shifting from lymphadenectomy to SLN biopsy in vulvar cancer surgery in the United States. SLN biopsy-incorporated treatment approach was not associated with worse survival compared to LND.
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http://dx.doi.org/10.1016/j.ygyno.2022.01.002DOI Listing
January 2022

Authors' reply re: Covariate analysis query: Hospital surgical volume-outcome relationship in caesarean hysterectomy for placenta accreta spectrum.

BJOG 2022 Jan 11. Epub 2022 Jan 11.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, New York, NY, USA.

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http://dx.doi.org/10.1111/1471-0528.17077DOI Listing
January 2022

Validation of the 2021 FIGO staging schema for advanced vulvar cancer.

Int J Gynecol Cancer 2022 Jan 7. Epub 2022 Jan 7.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, New York, New York, USA.

Objective: The International Federation of Gynecology and Obstetrics (FIGO) revised the vulvar cancer staging schema in 2021. Previous stage IIIA-B diseases were reclassified based on nodal size (≤5 mm for stage IIIA compared with >5 mm for stage IIIB), and previous stage IVA1 disease based on non-osseous organ extension was reclassified to stage IIIA whereas osseous extension remained as stage IVA. This study sought to validate the 2021 FIGO vulvar cancer staging schema.

Methods: This retrospective cohort study examined 889 women with stage III-IV vulvar cancer from 2010 to 2015 in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Stage shift and overall survival were assessed by comparing the 2021 and 2009 FIGO staging schemas.

Results: Stage shift occurred in 229 (25.8%) patients (upstaged 17.7% and downstaged 8.1%). When comparing the new and previous staging schemas, 5 year overall survival rates were 45.6% versus 48.9% for stage IIIA, 47.0% versus 44.2% for stage IIIB, and 13.9% versus 25.1% (interval change -11.2%) for stage IVA diseases. According to the revised staging schema, 5 year overall survival rates were similar for stage IVA and IVB diseases (13.9% vs 14.5%) and for stage IIIA and IIIB disease (45.6% vs 47.0%). For new stage IIIA disease, 5 year overall survival rates differed significantly based on the staging factors (nodal involvement vs non-nodal organ involvement, 48.9% vs 38.7%, difference 10.2%, p=0.038).

Conclusion: The 2021 FIGO staging schema results in one in four cases of advanced vulvar cancer being reclassified. Survival rates of patients with new stage IVA disease worsened significantly whereas those of patients with new stage IIIA disease were heterogenous based on the staging factors. The discriminatory ability of the revised 2021 FIGO staging schema for 5 year overall survival rate between patients with stage IIIA and IIIB tumors and those with IVA and IVB tumors is limited in this study population.
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http://dx.doi.org/10.1136/ijgc-2021-003168DOI Listing
January 2022

Medial Elbow Joint Space Gapping Associated with Repetitive Baseball Pitching in Preadolescent Baseball Players.

J Shoulder Elbow Surg 2021 Dec 27. Epub 2021 Dec 27.

Department of Rehabilitation, School of Allied Health Sciences, Kitasato University, Sagamihara, Japan.

Background: The baseball pitching motion creates valgus stress to the medial elbow, which contributes to increased medial elbow joint space gapping. The musculoskeletal systems of preadolescent baseball players are immature compared to those of adults, but it is unclear whether the repetitive pitching action causes an increase in medial elbow joint space gapping. This study aimed to examine differences in medial elbow joint space gapping based on the pitch count of preadolescent baseball players compared to those of adult players.

Methods: The participants were 11 healthy preadolescent baseball players and 12 college students with baseball experience. They threw 60 maximal-effort pitches arranged into four sets of 15 pitches. The medial elbow joint space was measured ultrasonographically with the forearm weight before pitching and following every set of 15 pitches. Repeated-measures analysis of variance and the Bonferroni post hoc test were used to compare the medial elbow joint space among the five pitching sets (before pitching and after 15, 30, 45, and 60 pitches) and between the groups of preadolescent baseball players and college students.

Results: There was no significant change in the medial elbow joint space gapping of the dominant elbow based on age/pitch count (F=0.42, P=0.796). There was a significant effect of pitch count (F = 30.28, P<0.001) and between-group effects (F=4.56, P=0.045). The medial elbow joint space gapping increased significantly after 60 pitches in preadolescent baseball players (P=0.023) and college students (P=0.021). The medial elbow joint space gapping in preadolescent baseball players was significantly wider than that in college students (P=0.007 before pitching, P=0.027 at 15 pitches).

Conclusion: Sixty repetitive pitches contributed to an increase in the medial elbow joint space gapping, regardless of age. The results of this study provide further evidence when considering pitching limitations.
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http://dx.doi.org/10.1016/j.jse.2021.11.009DOI Listing
December 2021

Epigenetic Dysregulation of Trophoblastic Gene Expression in Gestational Trophoblastic Disease.

Biomedicines 2021 Dec 17;9(12). Epub 2021 Dec 17.

Systems Biology of Reproduction Research Group, Research Centre for Natural Sciences, Institute of Enzymology, H-1117 Budapest, Hungary.

Gestational trophoblastic diseases (GTDs) have not been investigated for their epigenetic marks and consequent transcriptomic changes. Here, we analyzed genome-wide DNA methylation and transcriptome data to reveal the epigenetic basis of disease pathways that may lead to benign or malignant GTDs. RNA-Seq, mRNA microarray, and Human Methylation 450 BeadChip data from complete moles and choriocarcinoma cells were bioinformatically analyzed. Paraffin-embedded tissues from complete moles and control placentas were used for tissue microarray construction, DNMT3B immunostaining and immunoscoring. We found that DNA methylation increases with disease severity in GTDs. Differentially expressed genes are mainly upregulated in moles while predominantly downregulated in choriocarcinoma. DNA methylation principally influences the gene expression of villous trophoblast differentiation-related or predominantly placenta-expressed genes in moles and choriocarcinoma cells. Affected genes in these subsets shared focal adhesion and actin cytoskeleton pathways in moles and choriocarcinoma. In moles, cell cycle and differentiation regulatory pathways, essential for trophoblast/placental development, were enriched. In choriocarcinoma cells, hormone biosynthetic, extracellular matrix-related, hypoxic gene regulatory, and differentiation-related signaling pathways were enriched. In moles, we found slight upregulation of DNMT3B protein, a developmentally important de novo DNA methylase, which is strongly overexpressed in choriocarcinoma cells that may partly be responsible for the large DNA methylation differences. Our findings provide new insights into the shared and disparate molecular pathways of disease in GTDs and may help in designing new diagnostic and therapeutic tools.
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http://dx.doi.org/10.3390/biomedicines9121935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8698431PMC
December 2021

Oncologic Outcomes of Laparoscopic Radical Hysterectomy Using the No-Look No-Touch Technique for Early Stage Cervical Cancer: A Propensity Score-Adjusted Analysis.

Cancers (Basel) 2021 Dec 3;13(23). Epub 2021 Dec 3.

Department of Obstetrics and Gynecology, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.

We evaluated oncologic outcomes of laparoscopic radical hysterectomy using the no-look no-touch technique (NLNT). We analyzed patients with early stage (IA2, IB1, and IIA1, FIGO2008) cervical cancer treated between December 2014 and December 2019. The primary endpoint was disease-free survival (DFS). We compared the outcomes of the abdominal radical hysterectomy (ARH) and NLNT groups using a Cox model with inverse probability of treatment weighting (IPTW), according to propensity scores. We also evaluated NLNT's non-inferiority to ARH using an evaluation of heterogeneity between the results of the Laparoscopic Approach to Cervical Cancer (LACC) trial and our study. ARH and NLNT were performed in 118 and 113 patients, respectively. The median follow-up duration was 3.2 years. After IPTW adjustment, the 3-year DFS rates (NLNT 92.4%; ARH 94.0%) and overall survival rates did not differ significantly between the groups. Furthermore, the 3-year DFS rates for patients with tumor sizes ≥ 2 cm in the NLNT (85.0%) and ARH (90.3%) groups did not differ significantly. No significant heterogeneity was observed between the LACC trial and our study (I = 60.5%, = 0.111), although there was a trend toward a lower hazard ratio in our study. Laparoscopic radical hysterectomy using NLNT provides a favorable prognosis for early stage cervical cancer.
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http://dx.doi.org/10.3390/cancers13236097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8657300PMC
December 2021

Intraoperative tumor spill during minimally invasive hysterectomy for endometrial cancer: A survey study on experience and practice.

Eur J Obstet Gynecol Reprod Biol 2021 Dec 16;267:256-261. Epub 2021 Nov 16.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA. Electronic address:

Objective: Tumor spill during surgical treatment is associated with adverse oncologic outcomes in many solid tumors. However, in minimally invasive hysterectomy for endometrial cancer, intraoperative tumor spill has not been well studied. This study examined surgeon experiences and practices related to intraoperative tumor spill during minimally invasive hysterectomy for endometrial cancer.

Methods: A cross-sectional survey was conducted to the Society of Gynecologic Oncology. Participants were 220 U.S. gynecologic oncologists practicing minimally invasive hysterectomy for endometrial cancer. Interventions were 20 questions regarding surgeon demographics, surgical practice patterns (fallopian tubal ablation/ligation, intra-uterine manipulator use, and colpotomy approach), and tumor spill experience (uterine perforation with intra-uterine manipulator and tumor exposure during colpotomy).

Results: Nearly half of the responding surgeons completed subspeciality training >10 years ago (50.5%), and 74.1% had annual surgical volume of >40 cases. The majority of surgeons used an intra-uterine manipulator during minimally invasive hysterectomies for endometrial cancer (90.1%), and 87.2% of the users have experienced uterine perforation with an intra-uterine manipulator. Almost all surgeons performed colpotomy laparoscopically (95.9%), and nearly 60% had experienced tumor spill while making colpotomy (59.8%). Nearly 10-15% of surgeons have changed their postoperative therapy as a result of intraoperative uterine perforation (11.8%) or tumor spill (14.5%). Surgeons infrequently ablated or ligated fallopian tubes prior to performing the hysterectomy (14.1%).

Conclusion: Our survey study suggests that many surgeons experienced intraoperative tumor spillage during minimally invasive hysterectomy for endometrial cancer. These findings warrant further studies examining its incidence and impact on clinical outcomes.
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http://dx.doi.org/10.1016/j.ejogrb.2021.11.020DOI Listing
December 2021

Association between hospital treatment volume and survival of women with gynecologic malignancy in Japan: a JSOG tumor registry-based data extraction study.

J Gynecol Oncol 2022 Jan 1;33(1):e3. Epub 2021 Nov 1.

Department of Obstetrics and Gynecology, Tokai University School of Medicine, Kanagawa, Japan.

Objective: Associations between hospital treatment volume and survival outcomes for women with 3 types of gynecologic malignancies, and the trends and contributing factors for high-volume centers were examined.

Methods: The Japan Society of Obstetrics and Gynecology tumor registry databased retrospective study examined 206,845 women with 80,741, 73,647, and 52,457 of endometrial, cervical, and ovarian tumor, respectively, who underwent primary treatment in Japan between 2004 and 2015. Associations between the annual treatment volume and overall survival (OS) for each tumor type were examined using a multivariable Cox proportional hazards model with restricted cubic splines. Institutions were categorized into 3 groups (low-, moderate-, and high-volume centers) based on hazard risks.

Results: Hazard ratio (HR) for OS each the 3 tumors decreased with hospital treatment volume. The cut-off points of treatment volume were defined for high- (≥50, ≥51, and ≥27), moderate- (20-49, 20-50, and 17-26), and low-volume centers (≤19, ≤19, and ≤16) by cases/year for endometrial, cervical, and ovarian tumors, respectively. Multivariate analysis revealed younger age, rare tumor histology, and initial surgical management as contributing factors for women at high-volume centers (all, p<0.001). The proportion of high-volume center treatments decreased, whereas low-volume center treatments increased (all p<0.001). Treatment at high-volume centers improved OS than that at other centers (adjusted HR [aHR]=0.83, 95% confidence interval [CI]=0.78-0.88; aHR=0.78, 95% CI=0.75-0.83; and aHR=0.90, 95% CI=0.86-0.95 for endometrial, cervical, and ovarian tumors).

Conclusion: Hospital treatment volume impacted survival outcomes. Treatments at high-volume centers conferred survival benefits for women with gynecologic malignancies. The proportion of treatments at high-volume centers have been decreasing recently.
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http://dx.doi.org/10.3802/jgo.2022.33.e3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8728670PMC
January 2022

Sentinel lymph node biopsy for vulvar melanoma: trends in tumor stage-specific utilization.

Am J Obstet Gynecol 2021 Oct 29. Epub 2021 Oct 29.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, 2020 Zonal Ave., IRD 520, Los Angeles, CA 90033; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA. Electronic address:

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http://dx.doi.org/10.1016/j.ajog.2021.10.032DOI Listing
October 2021

Incorporation of vaginal brachytherapy to external beam radiotherapy in adjuvant therapy for high-risk early-stage cervical cancer: A comparative study.

Brachytherapy 2021 Oct 28. Epub 2021 Oct 28.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA. Electronic address:

Purpose: To examine trends, characteristics, and outcomes related to addition of vaginal brachytherapy (VBT) to external beam radiotherapy (EBRT) for adjuvant radiotherapy in high-risk early-stage cervical cancer.

Methods And Materials: This comparative study is a retrospective observational analysis of the National Cancer Institutes' Surveillance, Epidemiology, and End Results Program. Surgically treated women with stage T1-2 cervical cancer who had high-risk factors (nodal metastasis and/or parametrial invasion) and received adjuvant radiotherapy from 2000 to 2018 were examined. Propensity score inverse probability of treatment weighting was used to assess the survival estimates for addition of VBT use.

Results: Among 2470 women with high-risk factors receiving EBRT, 760 (30.8%) had additional VBT. During the study period, there was an increasing trend of VBT use from 27.4% to 36.1% (p< 0.001). In a multivariable analysis, year of diagnosis and high-risk tumor factors: parametrial involvement, large tumor size, and use of chemotherapy remained independent characteristics associated with VBT use (all, p< 0.05). In propensity score-weighted models, VBT use with EBRT and EBRT alone had comparable overall survival (5-year rates 73.8% vs. 77.4%, hazard ratio [HR] 1.07, 95% confidence interval [CI] 0.92-1.25). Nonsignificant association was also observed in squamous or nonsquamous tumors, young or old age, low or high nodal ratio, chemotherapy use, and simple or radical hysterectomy (all, p> 0.05). Lastly, the addition of VBT was not associated with cervical cancer-specific survival (subdistribution-HR 1.15, 95% CI 0.94-1.41).

Conclusions: Utilization of VBT with EBRT for adjuvant radiotherapy in high-risk early-stage cervical cancer is increasing in the United States. Addition of VBT was associated with neither overall survival nor cancer-specific survival.
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http://dx.doi.org/10.1016/j.brachy.2021.09.006DOI Listing
October 2021

Sentinel lymph node biopsy for stage II endometrial cancer: Recent utilization and outcome in the United States.

Gynecol Oncol 2022 Jan 30;164(1):46-52. Epub 2021 Oct 30.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, New York, NY, USA.

Objective: To examine trends and outcomes related to sentinel lymph node (SLN) biopsy for stage II endometrial cancer.

Methods: This is a retrospective observational cohort study querying the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. The study population was 6,314 women with T2 endometrial cancer who underwent hysterectomy from 2010-2018. Exposure allocation was based on nodal evaluation type: lymphadenectomy (LND; n=4,915, 77.8%), SLN biopsy (n=340, 5.4%), or no surgical nodal evaluation (n=1,059, 16.8%). The main outcomes were (i) trends and characteristics related to nodal evaluation assessed by multinomial regression, and (ii) overall survival (OS) assessed by an inverse probability of treatment weighting propensity score analysis. A sensitivity analysis was performed to examine concurrent LND in women who underwent SLN biopsy.

Results: The utilization of SLN biopsy increased from 1.6% to 16.1%, while the number of LND decreased from 81.5% to 65.7% between 2010-2018 (P<0.05). In multivariable analysis, the utilization of SLN biopsy increased 45% annually (adjusted-odds ratio 1.45, 95% confidence interval [CI] 1.37-1.54, P<0.001). The frequency of SLN biopsy alone exceeded the frequency of SLN biopsy with concurrent LND in 2017 (6.8% versus 3.4%), followed by continued increase in SLN biopsy alone (11.2% versus 4.9%) in 2018. In the weighted model, the 3-year OS rate was 79.9% for the SLN biopsy group and 78.6% for the LND group (hazard ratio 0.98, 95%Cl 0.80-1.20, P=0.831). Similarly, the SLN biopsy alone without concurrent LND had comparable OS compared to the LND group (hazard ratio 0.90, 95%CI 0.59-1.36, P=0.615).

Conclusion: Utilization of SLN biopsy in stage II endometrial cancer increased significantly over time, and SLN biopsy-incorporated nodal assessment was not associated with worsened short-term survival outcome.
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http://dx.doi.org/10.1016/j.ygyno.2021.10.085DOI Listing
January 2022

Racial and ethnic disparity in characteristics and outcomes of women with placenta accreta spectrum: a comparative study.

Reprod Sci 2021 Oct 29. Epub 2021 Oct 29.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, 2020 Zonal Avenue, IRD 520, Los Angeles, CA, 90033, USA.

Placenta accreta spectrum (PAS) refers to the spectrum of diagnoses involving abnormally and morbidly adherent trophoblastic tissue to the gravid uterus. These disorders are associated with significant maternal morbidity and mortality. While race/ethnicity is known to impact pregnancy outcomes, racial disparities have not been previously examined in women with PAS. The objective of current study was to compare patient characteristics and perioperative outcomes of women with PAS who underwent cesarean delivery across race/ethnicity. This is a comparative study that retrospectively queried the National Inpatient Sample, a hospital-based inpatient database in the USA. The study cohort was women diagnosed with PAS who underwent cesarean delivery from 10/2015 to 12/2018. The exposure group was race/ethnicity. Main outcomes were (i) patient/pregnancy characteristics and (ii) surgical morbidity for cesarean delivery, assessed in multivariable analysis. A total of 10,535 women comprised the study cohort (White n = 5,230 [49.6%], Black n = 2,045 [19.4%], Hispanic n = 2,540 [24.1%], and Asian n = 720 [6.8%]). Patient demographics, pregnancy characteristics, and hospital factors for the non-White groups significantly differed compared to the White group. Older age, obesity, diabetes, placenta previa, percreta, non-elective surgery, lower median household income, and Medicaid particularly represented the non-White groups. When perioperative outcomes were compared, non-White women were more likely to have any measured complications, hemorrhage/transfusion, and shock/coagulopathy compared to White women. Various sensitivity analyses redemonstrated the main cohort results. In conclusion, this study suggests that there were significant disparities in patient characteristics and outcomes of women with PAS across race/ethnicity.
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http://dx.doi.org/10.1007/s43032-021-00781-2DOI Listing
October 2021

In Reply: Is twin gestation an independent risk factor for placenta accreta spectrum: a response.

Am J Obstet Gynecol 2021 Oct 23. Epub 2021 Oct 23.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA; Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA. Electronic address:

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http://dx.doi.org/10.1016/j.ajog.2021.10.024DOI Listing
October 2021

Minimally Invasive Surgery and Surgical Volume-Specific Survival and Perioperative Outcome: Unmet Need for Evidence in Gynecologic Malignancy.

J Clin Med 2021 Oct 19;10(20). Epub 2021 Oct 19.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA 90033, USA.

This study examined the effect of hospital surgical volume on oncologic outcomes in minimally invasive surgery (MIS) for gynecologic malignancies. The objectives were to assess survival outcomes related to hospital surgical volume and to evaluate perioperative outcomes and examine non-gynecologic malignancies. Literature available from the PubMed, Scopus, and the Cochrane Library databases were systematically reviewed. All surgical procedures including gynecologic surgery with hospital surgical volume information were eligible for analysis. Twenty-three studies met the inclusion criteria, and nine gastro-intestinal studies, seven genitourinary studies, four gynecological studies, two hepatobiliary studies, and one thoracic study were reviewed. Of those, 11 showed a positive volume-outcome association for perioperative outcomes. A study on MIS for ovarian cancer reported lower surgical morbidity in high-volume centers. Two studies were on endometrial cancer, of which one showed lower treatment costs in high-volume centers and the other showed no association with perioperative morbidity. Another study examined robotic-assisted radical hysterectomy for cervical cancer and found no volume-outcome association for surgical morbidity. There were no gynecologic studies examining the association between hospital surgical volume and oncologic outcomes in MIS. The volume-outcome association for oncologic outcome in gynecologic MIS is understudied. This lack of evidence calls for further studies to address this knowledge gap.
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http://dx.doi.org/10.3390/jcm10204787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8537091PMC
October 2021

Utilizations and outcomes of intra-arterial balloon occlusion at cesarean hysterectomy for placenta accreta spectrum.

Acta Obstet Gynecol Scand 2021 Dec 8;100(12):2234-2243. Epub 2021 Oct 8.

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA.

Introduction: This study examined national-level trends, characteristics, and perioperative outcomes of women who had intra-arterial balloon occlusion at cesarean hysterectomy for placenta accreta spectrum (PAS).

Material And Methods: This was a population-based retrospective observational study that queried the National Inpatient Sample from October 2015 to December 2018. Study population was women who underwent hysterectomy at cesarean delivery for PAS (n = 6440 in 806 centers). Exposure allocation was the use of intra-arterial balloon occlusion. Main outcome measures were (a) characteristics associated with intra-arterial balloon occlusion use, and (b) perioperative outcome including hemorrhage, blood transfusion, coagulopathy, shock, urinary tract injury, intra-arterial balloon occlusion-related complication (arterial injury, arterial thrombosis, and lower extremities ischemia), and death, assessed in multivariable analysis.

Results: Intra-arterial balloon occlusion was used in 420 (6.5%) women in 64 (7.9%) centers. Utilization of intra-arterial balloon occlusion during cesarean hysterectomy for placenta accreta decreased significantly over time (from 6.3% to 3.1%, p < 0.001), but not in placenta increta (from 12.8% to 9.3%, p = 0.204) or placenta percreta (from 21.3% to 17.5%, p = 0.344). In a multivariable analysis, patient factors (younger age, earlier year, obesity, diabetes mellitus), pregnancy factors (placenta increta/percreta, previous cesarean delivery, placenta previa, and early gestational age), and facility factors (large bed capacity, urban teaching status, and Northeast/West regions) represented the independent characteristics for using the intra-arterial balloon occlusion (all, p < 0.05). In a classification-tree model, the absolute difference in intra-arterial balloon occlusion use among 18 utilization patterns was 48% (range, 0%-48%). In perioperative outcome analysis, women who received intra-arterial balloon occlusion were more likely to have coagulopathy (adjusted odds ratio [aOR] 3.43) and arterial thrombosis (aOR 9.82) in placenta accreta, but less likely to have hemorrhage (aOR 0.25) in placenta increta, and blood transfusion (aOR 0.60) and urinary tract injury (aOR 0.28) in placenta percreta compared with those who did not (all, p < 0.05).

Conclusions: There is a wide range in the utilization of intra-arterial balloon occlusion at cesarean hysterectomy for PAS based on patient, pregnancy, and facility factors, which implies that there is a lack of universal practice guidelines in this surgical procedure. Whether the use of intra-arterial balloon occlusion in the severe forms of PAS improves surgical outcome merits further investigation.
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http://dx.doi.org/10.1111/aogs.14266DOI Listing
December 2021

Reduced Brain Activation in Response to Social Cognition Tasks in Autism Spectrum Disorder with and without Depression.

Neuropsychiatr Dis Treat 2021 28;17:3015-3024. Epub 2021 Sep 28.

Research Center for Child Mental Development, Chiba University, Chiba, Japan.

Purpose: In clinical settings, diagnosing comorbid depression in individuals with autism spectrum disorder (ASD) is often difficult. Neuroimaging studies have reported reduced activation of frontal and temporal regions during emotional face recognition task (EFRT) in ASD and depression. However, to the best of our knowledge, no study has examined differences in frontotemporal activation during EFRT between ASD with and without comorbid depression. We aimed to compare the frontotemporal hemodynamic responses to the EFRT in ASD with and without depression and to find clues to help in discriminating the characteristics between them.

Patients And Methods: In 24 drug-naïve young adults with ASD (12 with depression [ASD-Dep(+)] and 12 without depression [ASD-Dep(-)]) and 12 with typical development (TD), frontotemporal hemodynamic responses during an EFRT were measured using functional near-infrared spectroscopy (fNIRS).

Results: The ASD groups showed reduced activation during EFRT than the TD group in the right ventrolateral prefrontal cortex (VLPFC). Moreover, the ASD-Dep(+) group showed reduced activation during EFRT than the ASD-Dep(-) group in the right anterior temporal cortex (aTC), and reduced activation than the TD group in the left VLPFC.

Conclusion: The observed results might reflect reduced regional activation in ASD and ASD with comorbid depression.
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http://dx.doi.org/10.2147/NDT.S327608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487275PMC
September 2021

Proposal of a simple 2-hand technique at cesarean hysterectomy for placenta accreta spectrum.

Arch Gynecol Obstet 2021 Oct 5. Epub 2021 Oct 5.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, 2020 Zonal Avenue, IRD 520, Los Angeles, CA, 90033, USA.

Placenta accreta spectrum (PAS) encompasses a range of disorders of placental trophoblastic tissue that is morbidly adherent to the underlying gravid uterus. Women with PAS commonly undergo surgical treatment with hysterectomy at cesarean delivery that is associated with significant surgical morbidity and mortality. Increased vascularity due to gestational change and the abnormally enlarged lower uterine segment due to the location of placenta make the surgery complex and morbid. Here, we propose a simple 2-hand technique that can be used to improve surgical outcomes of cesarean hysterectomy for PAS. Unlike the ordinary hysterectomy where the transection of the cardinal ligament is started at the isthmus below the low uterine segment, the proposed 2-hand technique allows transection of the cardinal ligament at the level of the lower uterine segment below the placental bed. This minimizes blood loss that may be associated with serial transection of cardinal ligament which occurs when it is transected at or above the placenta level. This surgical approach starts with demarcation of 3 anatomical landmarks [rectum (posterior aspect), ureters (lateral aspect), and bladder (anterior aspect)] in postero-anterior progression. Complete de-serosalization of posterior low uterine segment allows lateralization of the ureter and enables the uterus to be mobilized antero-caudally where the surgeon's hand can reach below the placental bed. After the bladder flap creation to the level of endopelvic fascia, the surgeon's two hands are placed antero-posteriorly at low uterine segment below the placental bed. The fingertips of both hands meet at the cardinal ligament below placenta at the level of the upper cervix. At this point the two hands are gently moved upwards, carrying the placenta-containing low uterine segment. This step enables creation of a safe anatomical distance from surrounding structures and isolation of the cardinal ligament where surgical clamp can be applied to transect the cardinal ligament.
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http://dx.doi.org/10.1007/s00404-021-06260-yDOI Listing
October 2021

Secondary haematologic malignancies in women with ovarian cancer receiving poly-ADP ribose polymerase inhibitor therapy.

Eur J Cancer 2021 11 3;157:59-62. Epub 2021 Sep 3.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, New York, NY, USA.

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http://dx.doi.org/10.1016/j.ejca.2021.08.016DOI Listing
November 2021

Proposing a molecular classification associated with hypercoagulation in ovarian clear cell carcinoma.

Gynecol Oncol 2021 11 25;163(2):327-333. Epub 2021 Aug 25.

Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Background: Although ovarian clear cell carcinoma (CCC) is associated with high incidence of thromboembolism, the clinicopathological and biological significance of hypercoagulable status in CCC remains unclear.

Materials And Methods: We retrospectively analyzed pretreatment D-dimer levels, thromboembolic status, and clinical outcome of 125 CCCs in the discovery set and 143 CCCs in two other independent validation sets. Next, we performed RNA sequencing of 93 CCCs and compared coagulation-related gene profiles with 2492 pan-cancer data. We investigated differences in molecular characteristics of CCC subclasses based on coagulation status.

Results: In the discovery dataset, D-dimer elevation above the normal range was significantly associated with shorter progression-free and overall survival, irrespective to thromboembolic status. Multivariate analysis identified D-dimer elevation and clinical stage as an independent prognostic factors. We confirmed the prognostic significance of D-dimer elevation in the validation sets. Tissue factor and IL6, which are considered key elements of cancer-induced hypercoagulation, were highly expressed in CCC than in other cancers regardless of D-dimer level. Higher activity of various oncogenic pathways was observed in CCC with compared to without D-dimer elevation. Moreover, hierarchical cluster analysis divided 57 CCCs with D-dimer elevation into immunologically hot and cold tumor subtypes. Hot tumors were characterized by enrichment of T-cell inflamed phenotype, inflammation, the epithelial-mesenchymal transition, and high serum levels of CRP, and cold tumors by enrichment of cell cycle and MYC pathways.

Conclusions: CCC represents hypercoagulable disease and elevate D-dimer is a prognostic factor for decreased survival in CCC. D-dimer high CCC has distinct molecular characteristics into the inflammatory-driven pathway (hot tumor) and the immune-suppressive pathway (cold tumor). Treatment implication of our proposed molecular classification merits further investigation.
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http://dx.doi.org/10.1016/j.ygyno.2021.08.009DOI Listing
November 2021

Effects of aspirin and statin use on venous thromboembolism prophylaxis and survival in patients with endometrial cancer.

Expert Opin Drug Saf 2021 Sep 6:1-13. Epub 2021 Sep 6.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA.

Introduction: Acetylsalicylic acid (aspirin) and statins are commonly used to manage and prevent cardiovascular diseases. Recent studies have suggested the benefits of aspirin or statin use in venous thromboembolism (VTE) prophylaxis and survival outcome improvement in women with endometrial cancer.

Areas Covered: In this study, we reviewed the effects of aspirin or statin use on VTE prophylaxis and survival outcome in women with endometrial cancer.

Expert Opinion: Among women with endometrial cancer, aspirin use exerted a modest effect on VTE prophylaxis, whereas statin use was associated with a decreased prevalence of VTE, especially in women with obesity and type II cancer, compared with those in non-users. Aspirin use improved cause-specific survival in women with endometrial cancer, aged less than 60 years, who were obese and presented with type I cancer. Statin use was associated with better cause-specific survival in women with type II cancer. The combination of aspirin and statins may be the most effective strategy in improving on VTE prophylaxis and survival outcomes in obese women with type II cancer. Targeting of the appropriate population with endometrial cancer may enhance the efficacy of aspirin or statins on VTE prophylaxis and survival outcomes in women with endometrial cancer.
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http://dx.doi.org/10.1080/14740338.2021.1973427DOI Listing
September 2021

Immunohistochemical analysis of glassy cell carcinoma of the cervix reveals robust lymphocyte infiltrate and the expression of targetable inhibitory immune checkpoints.

Arch Gynecol Obstet 2021 Aug 15. Epub 2021 Aug 15.

Department of Translational Genomics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Objective: To validate our previous findings of high-level EGFR expression in GCCC using an expanded cohort of specimens and to further examine the molecular and cellular features of this aggressive malignancy to identify potentially actionable therapeutic targets.

Methods: The SEER database was queried to obtain the epidemiological data regarding the current national survival trends for GCCC. Immunohistochemistry (IHC) was used to examine the expression of EGFR, PD-1, and PD-L1. CiberSort analysis was used to analyze a previously published RNA-sequencing dataset obtained from a single patient diagnosed with GCCC.

Results: In comparison to squamous cell carcinomas and adenocarcinoma/adenosquamous carcinomas, GCCC was observed in younger patients (p < 0.001) and demonstrated inferior survival (p < 0.001). All (100%) of the specimens (8/8) exhibited immunoreactivity when stained for CD3ε (T-cell marker), EGFR, PD-1, and PD-L1 whereas CTLA4 expression was not detected. Analysis of RNA-sequencing data revealed that cetuximab and erlotinib altered the chemokine profile, lymphocyte abundance, and expression of inhibitory immune checkpoints in a single patient when combined with cytotoxic chemotherapy in a single patient.

Conclusions: The data from this descriptive study suggests that immune checkpoint blockade, whether single agent or in combination, may be a suitable therapeutic option for a disease for which targeted approaches do not currently exist.
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http://dx.doi.org/10.1007/s00404-021-06164-xDOI Listing
August 2021

ACVR1 extends inflammatory responses in human induced pluripotent stem cell-derived macrophages.

Bone 2021 12 24;153:116129. Epub 2021 Jul 24.

Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Francisco, CA, USA; The Institute for Human Genetics, University of California, San Francisco, CA, USA; The Program in Craniofacial Biology, University of California, San Francisco, CA, USA. Electronic address:

Macrophages play crucial roles in many human disease processes. However, obtaining large numbers of primary cells for study is often difficult. We describe 2D and 3D methods for directing human induced pluripotent stem cells (hiPSCs) into macrophages (iMACs). iMACs generated in 2D culture showed functional similarities to human primary monocyte-derived M2-like macrophages, and could be successfully polarized into a M1-like phenotype. Both M1- and M2-like iMACs showed phagocytic activity and reactivity to endogenous or exogenous stimuli. In contrast, iMACs generated by a 3D culture system showed mixed M1- and M2-like functional characteristics. 2D-iMACs from patients with fibrodysplasia ossificans progressiva (FOP), an inherited disease with progressive heterotopic ossification driven by inflammation, showed prolonged inflammatory cytokine production and higher Activin A production after M1-like polarization, resulting in dampened responses to additional LPS stimulation. These results demonstrate a simple and robust way of creating hiPSC-derived M1- and M2-like macrophage lineages, while identifying macrophages as a source of Activin A that may drive heterotopic ossification in FOP.
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http://dx.doi.org/10.1016/j.bone.2021.116129DOI Listing
December 2021

Predictors of subsequent pregnancy following medical treatment in obese women with complex atypical hyperplasia.

Arch Gynecol Obstet 2021 Jul 26. Epub 2021 Jul 26.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, 2020 Zonal Avenue, IRD 520, Los Angeles, CA, 90033, USA.

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http://dx.doi.org/10.1007/s00404-021-06150-3DOI Listing
July 2021

Association between hysterectomy wait-time and all-cause mortality for micro-invasive cervical cancer: treatment implications during the coronavirus pandemic.

Arch Gynecol Obstet 2021 Jul 23. Epub 2021 Jul 23.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, 161 Fort Washington Avenue, 8th Floor, New York, NY, 10032, USA.

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http://dx.doi.org/10.1007/s00404-021-06151-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301734PMC
July 2021

Characteristics and outcomes of women with adenocarcinoma versus squamous cell carcinoma of the vulva: A Japanese Gynecologic Oncology Group study.

Eur J Surg Oncol 2021 Dec 9;47(12):3188-3193. Epub 2021 Jul 9.

Department of Obstetrics and Gynecology, Niigata University School of Medicine, Niigata, Japan.

Objective: Studies on vulvar adenocarcinoma are lacking. Thus, we aimed to compare the characteristics and survival outcomes between vulvar adenocarcinoma and squamous cell carcinoma (SCC).

Methods: This was a preplanned sub-analysis of a previously organized nationwide retrospective observational study in Japan conducted between 2001 and 2010 (JGOG-1075S). Surgically treated women with stage I-IV vulvar invasive adenocarcinoma were compared to those with SCC. Multivariable analysis was performed to identify patient and tumor characteristics related to adenocarcinoma. Inverse probability of treatment weighting was used to balance the background differences, and a Cox proportional hazards regression model was fitted to estimate the effect of the histological type on survival.

Results: Forty-eight women with adenocarcinoma were compared with 537 women with SCC. On multivariable analysis, women with adenocarcinoma were younger (median age, 64.5 vs. 70 years, adjusted odds ratio [OR] per age 0.975, 95% confidence interval [CI] 0.955-0.995, P = 0.016) and had higher positive surgical margin rates (31.2% vs. 18.4%, adjusted OR 2.376, 95% CI 1.188-4.754, P = 0.014) than those with SCC. However, according to the weighted model, the survival outcomes were comparable (hazard ratio for progression-free survival, 1.088, 95% CI 0.740-1.601, P = 0.667 and hazard ratio for overall survival, 1.008, 95% CI 0.646-1.573, P = 0.973). Similar associations were observed when the cohort was stratified by age (≤70 or >70 years), stage (I-II or III-IV), and surgical margin (negative or positive) (all, P > 0.05).

Conclusion: Vulvar adenocarcinoma is characterized by a younger age at diagnosis and higher positive surgical margin rates than SCC, but the survival outcomes are comparable.
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http://dx.doi.org/10.1016/j.ejso.2021.07.002DOI Listing
December 2021

The influence of obesity on incidence of complications in patients hospitalized with ovarian hyperstimulation syndrome.

Arch Gynecol Obstet 2021 Jul 9. Epub 2021 Jul 9.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, 2020 Zonal Avenue, IRD 520, Los Angeles, CA, 90033, USA.

Objective: To study the impact of body habitus on risk of complications resulting from ovarian hyperstimulation syndrome (OHSS) in hospitalized patients.

Methods: This is a retrospective observational study examining the National Inpatient Sample between January 2012 and September 2015. Patients were women < 50 years of age diagnosed with OHSS, classified as non-obese, class I-II obesity, or class III obesity. Intervention included multinomial logistic regression to identify factors associated with obesity and binary logistic regression for independent risk factors for complications. Main outcome measures were incidence of (i) any or (ii) multiple complication(s).

Results: Of 2745 women hospitalized with OHSS, 2440 (88.9%) were non-obese, 155 (5.6%) had class I-II obesity, and 150 (5.5%) had class III obesity. Obese women (either class I-II or III) had a higher degree of comorbidity, had lower incomes, and were less likely to have private insurance than non-obese women (all P < 0.001). Obese women had lower rates of OHSS-related complications than non-obese women (any complication: non-obese 65.2%, class I-II 54.8%, and class III 46.7%, P < 0.001; and multiple complications: non-obese 38.5%, class I-II 32.3%, and class III 20.0%, P < 0.001). In the multivariable model, obesity remained independently associated with a decreased risk of complications (class I-II odds ratio 0.57, 95% confidence interval 0.39-0.83, P = 0.003; class III odds ratio 0.30, 95% confidence interval 0.20-0.44, P < 0.001). Obese women were also less likely to require paracentesis (non-obese 32.8%, class I-II 9.7%, and class III 13.3%, P < 0.001).

Conclusion: Our study suggests that obesity is associated with decreased OHSS-related complication rates in hospitalized patients.
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http://dx.doi.org/10.1007/s00404-021-06124-5DOI Listing
July 2021

Intraoperative Rupture of the Ovarian Capsule in Early-Stage Ovarian Cancer: A Meta-analysis.

Obstet Gynecol 2021 08;138(2):261-271

Columbia University College of Physicians and Surgeons, New York, New York; Duke University Medical Center, Durham, North Carolina; the Herbert Irving Comprehensive Cancer Center, New York, New York; New York Presbyterian Hospital, New York, New York; the Department of Obstetrics and Gynecology, Tokai University, Kanagawa, Japan; and the Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, California.

Objective: To examine the effects of intraoperative ovarian capsule rupture on progression-free survival and overall survival in women who are undergoing surgery for early-stage ovarian cancer.

Data Sources: MEDLINE using PubMed, EMBASE (Elsevier), ClinicalTrials.gov, and Scopus (Elsevier) were searched from inception until August 11, 2020.

Methods Of Study Selection: High-quality studies reporting survival outcomes comparing ovarian capsule rupture to no capsule rupture among patients with early-stage epithelial ovarian cancer who underwent surgical management were abstracted. Study quality was assessed with the Newcastle-Ottawa Scale, and studies with scores of at least 7 points were included.

Tabulation, Integration, And Results: The data were extracted independently by multiple observers. Random-effects models were used to pool associations and to analyze the association between ovarian capsule rupture and oncologic outcomes. Seventeen studies met all the criteria for inclusion in the meta-analysis. Twelve thousand seven hundred fifty-six (62.6%) patients did not have capsule rupture and had disease confined to the ovary on final pathology; 5,532 (33.7%) patients had intraoperative capsule rupture of an otherwise early-stage ovarian cancer. Patients with intraoperative capsule rupture had worse progression-free survival (hazard ratio [HR] 1.92, 95% CI 1.34-2.76, P<.001), with moderate heterogeneity (I2=41%, P=.07) when compared with those without capsule rupture. Pooled results from these studies showed a worse overall survival (HR 1.48, 95% CI 1.15-1.91, P=.003), with moderate heterogeneity (I2=53%, P=.02) when compared with patients without intraoperative capsule rupture. This remained significant in a series of sensitivity analyses.

Conclusion: This systematic review and meta-analysis of high-quality observational studies shows that intraoperative ovarian capsule rupture results in decreased progression-free survival and overall survival in women with early-stage ovarian cancer who are undergoing initial surgical management.

Systematic Review Registration: PROSPERO, CRD42021216561.
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http://dx.doi.org/10.1097/AOG.0000000000004455DOI Listing
August 2021
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