Cesarean hysterectomy for placenta accreta spectrum: Surgeon specialty-specific assessment.

OBJECTIVE: To assess (i) clinical and pregnancy characteristics, (ii) patterns of surgical procedures, and (iii) surgical morbidity associated with cesarean hysterectomy for placenta accreta spectrum based on the specialty of the attending surgeon. METHODS: The Premier Healthcare Database was queried retrospectively to study patients with placenta accreta spectrum who underwent cesarean delivery and concurrent hysterectomy from 2016 to 2020. Surgical morbidity was assessed with propensity score inverse probability of treatment weighting based on surgeon specialty for hysterectomy: general obstetrician-gynecologists, maternal-fetal medicine specialists, and gynecologic oncologists. RESULTS: A total of 2240 cesarean hysterectomies were studies. The most common surgeon type was general obstetrician-gynecologist (n = 1534, 68.5%), followed by gynecologic oncologist (n = 532, 23.8%) and maternal-fetal medicine specialist (n = 174, 7.8%). Patients in the gynecologic oncologist group had the highest rate of placenta increta or percreta, followed by the maternal-fetal medicine specialist and general obstetrician-gynecologist groups (43.4%, 39.6%, and 30.6%, P < .001). In a propensity score-weighted model, measured surgical morbidity was similar across the three subspecialty groups, including hemorrhage / blood transfusion (59.4-63.7%), bladder injury (18.3-24.0%), ureteral injury (2.2-4.3%), shock (8.6-10.5%), and coagulopathy (3.3-7.4%) (all, P > .05). Among the cesarean hysterectomy performed by gynecologic oncologist, hemorrhage / transfusion rates remained substantial despite additional surgical procedures: tranexamic acid / ureteral stent (60.4%), tranexamic acid / endo-arterial procedure (76.2%), ureteral stent / endo-arterial procedure (51.6%), and all three procedures (55.4%). Tranexamic acid administration with ureteral stent placement was associated with decreased bladder injury (12.8% vs 23.8-32.2%, P < .001). CONCLUSION: These data suggest that patient characteristics and surgical procedures related to cesarean hysterectomy for placenta accreta spectrum differ based on surgeon specialty. Gynecologic oncologists appear to manage more severe forms of placenta accreta spectrum. Regardless of surgeon's specialty, surgical morbidity of cesarean hysterectomy for placenta accreta spectrum is significant.

Significance of tumor size and number of positive nodes in patients with FIGO 2018 stage IIIC1 cervical cancer.

OBJECTIVE: This study aimed to investigate the prognostic significance of tumor size and number of positive pelvic lymph nodes (PLN) in International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IIIC1 cervical cancer patients. METHODS: Clinical data from 626 women with cervical cancer treated at Osaka International Cancer Center in 2010-2020 were retrospectively reviewed. Using the cutoff value obtained on the receiver operating characteristic analysis, the prognostic significance of tumor size and number of positive PLN in stage IIIC1 patients was first evaluated via uni- and multivariate analyses. Then, the impact of incorporating tumor size and number of positive PLN into the FIGO staging system was investigated using the Kaplan-Meier method. RESULTS: Among 196 women with Stage IIIC1 disease, larger tumors (>4 cm) and multiple PLN metastases (≥4) were independent predictors of progression-free survival (PFS) in patients with stage IIIC1 cervical cancer. The PFS of patients with stage IIIC1 disease was inversely associated with the number of risk factors. Although patients with stage IIIC1 disease had significantly increased survival rates compared to those with stage IIIA or IIIB disease in the original FIGO 2018 staging system, this reversal phenomenon was resolved by incorporating larger tumors (>4 cm) and multiple PLN metastases (≥4) into the revised staging system. CONCLUSIONS: Incorporating tumor size and number of metastatic lymph nodes into the FIGO staging system allows additional risk stratification for women with stage IIIC1 cervical cancer and improves survival prediction performance.

Intrauterine manipulator use during laparoscopic hysterectomy for endometrial cancer: association for pathological factors and oncologic outcomes.

OBJECTIVE: To examine the association between intrauterine manipulator use and pathological factors and oncologic outcomes in patients with endometrial cancer who had laparoscopic hysterectomy in Japan. METHODS: This was a nationwide retrospective cohort study of the tumor registry of the Japan Society of Obstetrics and Gynecology. Study population was 3846 patients who had laparoscopic hysterectomy for endometrial cancer from January 2015 to December 2017. An automated 1-to-1 propensity score matching with preoperative and intraoperative demographics was performed to assess postoperative pathological factors associated with the intrauterine manipulator. Survival outcomes were assessed by accounting for possible pathological mediators related to intrauterine manipulator use. RESULTS: Most patients had preoperative stage I disease (96.5%) and grade 1-2 endometrioid tumors (81.9%). During the study period, 1607 (41.8%) patients had intrauterine manipulator use and 2239 (58.2%) patients did not. In the matched cohort, the incidences of lymphovascular space invasion in the hysterectomy specimen were 17.8% in the intrauterine manipulator group and 13.3% in the non-manipulator group. Intrauterine manipulator use was associated with a 35% increased odds of lymphovascular space invasion (adjusted odds ratio 1.35, 95% confidence interval (CI) 1.08 to 1.69). The incidences of malignant cells identified in the pelvic peritoneal cytologic sample at hysterectomy were 10.8% for the intrauterine manipulator group and 6.4% for the non-manipulator group. Intrauterine manipulator use was associated with a 77% increased odds of malignant peritoneal cytology (adjusted odds ratio 1.77, 95% Cl 1.29 to 2.31). The 5 year overall survival rates were 94.2% for the intrauterine manipulator group and 96.6% for the non-manipulator group (hazard ratio (HR) 1.64, 95% Cl 1.12 to 2.39). Possible pathological mediators accounted HR was 1.36 (95%Cl 0.93 to 2.00). CONCLUSION: This nationwide analysis of predominantly early stage, low-grade endometrial cancer in Japan suggested that intrauterine manipulator use during laparoscopic hysterectomy for endometrial cancer may be associated with an increased risk of lymphovascular space invasion and malignant peritoneal cytology. Possible mediator effects of intrauterine manipulator use on survival warrant further investigation, especially with a prospective setting.

Opportunistic Salpingectomy at the Time of Laparoscopic Cholecystectomy for Ovarian Cancer Prevention: A Cost-effectiveness Analysis.

OBJECTIVE: To perform a cost-effectiveness analysis to examine the utility and effectiveness of OS performed at the time of elective cholecystectomy [laparoscopic cholecystectomy (LAP-CHOL)]. SUMMARY BACKGROUND DATA: OS has been adopted as a strategy to reduce the risk of ovarian cancer in women undergoing hysterectomy and tubal sterilization, although the procedure is rarely performed as a risk reducing strategy during other abdominopelvic procedures. METHODS: A decision model was created to examine women 40, 50, and 60 years of age undergoing LAP-CHOL with or without OS. The lifetime risk of ovarian cancer was assumed to be 1.17%, 1.09%, and 0.92% for women age 40, 50, and 60 years, respectively. OS was estimated to provide a 65% reduction in the risk of ovarian cancer and to require 30 additional minutes of operative time. We estimated the cost, quality-adjusted life-years, ovarian cancer cases and deaths prevented with OS. RESULTS: The additional cost of OS at LAP-CHOL ranged from $1898 to 1978. In a cohort of 5000 women, OS reduced the number of ovarian cancer cases by 39, 36, and 30 cases and deaths by 12, 14, and 16 in the age 40-, 50-, and 60-year-old cohorts, respectively. OS during LAP-CHOL was cost-effective, with incremental cost-effectiveness ratio of $11,162 to 26,463 in the 3 age models. In a probabilistic sensitivity analysis, incremental cost-effectiveness ratio for OS were less than $100,000 per quality-adjusted life-years in 90.5% or more of 1000 simulations. CONCLUSIONS: OS at the time of LAP-CHOL may be a cost-effective strategy to prevent ovarian cancer among average risk women.

Placenta previa percreta with surrounding organ involvement: a proposal for management.

Placenta accreta spectrum encompasses cases where the placenta is morbidly adherent to the myometrium. Placenta percreta, the most severe form of placenta accreta spectrum (grade 3E), occurs when the placenta invades through the myometrium and possibly into surrounding structures next to the uterine corpus. Maternal morbidity of placenta percreta is high, including severe maternal morbidity in 82.1% and mortality in 1.4% in the recent nationwide U.S. statistics. Although cesarean hysterectomy is commonly performed for patients with placenta accreta spectrum, conservative management is becoming more popular because of reduced morbidity in select cases. Treatment of grade 3E disease involving the urinary bladder, uterine cervix, or parametria is surgically complicated due to the location of the invasive placenta deep in the maternal pelvis. Cesarean hysterectomy in this setting has the potential for catastrophic hemorrhage and significant damage to surrounding organs. We propose a step-by-step schema to evaluate cases of grade 3E disease and determine whether immediate hysterectomy or conservative management, including planned delayed hysterectomy, is the most appropriate treatment option. The approach includes evaluation in the antenatal period with ultrasound and magnetic resonance imaging to determine suspicion for placenta previa percreta with surrounding organ involvement, planned cesarean delivery with a multidisciplinary team including experienced pelvic surgeons such as a gynecologic oncologist, intra-operative assessment including gross surgical field exposure and examination, cystoscopy, and consideration of careful intra-operative transvaginal ultrasound to determine the extent of placental invasion into surrounding organs. This evaluation helps decide the safety of primary cesarean hysterectomy. If safely resectable, additional considerations include intra-operative use of uterine artery embolization combined with tranexamic acid injection in cases at high risk for pelvic hemorrhage and ureteral stent placement. Availability of resuscitative endovascular balloon occlusion of the aorta is ideal. If safe resection is concerned, conservative management including planned delayed hysterectomy at around 4 weeks from cesarean delivery in stable patients is recommended.

The association between uterine adenomyosis and adverse obstetric outcomes: A propensity score-matched analysis.

INTRODUCTION: This study examined obstetric outcomes in patients diagnosed with uterine adenomyosis. MATERIAL AND METHODS: This historical cohort study queried the Healthcare Cost and Utilization Project's National Inpatient Sample. The study population was all hospital deliveries in women aged 15-54 years between January 2016 and December 2019. The exposure was a diagnosis of uterine adenomyosis. The main outcome measures were obstetric characteristics, including placenta previa, placenta accreta spectrum, and placental abruption. Secondary outcomes were delivery complications including severe maternal morbidity. Analytic steps to assess these outcomes included (i) a 1-to-N propensity score matching to mitigate and balance prepregnancy confounders to assess obstetric characteristics, followed by (ii) an adjusting model with preselected pregnancy and delivery factors to assess maternal morbidity. Sensitivity analyses were also performed with restricted cohorts to account for prior uterine scar, uterine myoma, and extra-uterine endometriosis. RESULTS: After propensity score matching, 5430 patients with adenomyosis were compared to 21 720 patients without adenomyosis. Adenomyosis was associated with an increased odds of placenta accreta spectrum (adjusted-odds ratio [aOR] 3.07, 95% confidence interval [CI] 2.01-4.70), placenta abruption (aOR 3.21, 95% CI: 2.60-3.98), and placenta previa (aOR 5.08, 95% CI: 4.25-6.06). Delivery at <32 weeks of gestation (aOR 1.48, 95% CI: 1.24-1.77) and cesarean delivery (aOR 7.72, 95% CI: 7.04-8.47) were both increased in women with adenomyosis. Patients in the adenomyosis group were more likely to experience severe maternal morbidity at delivery compared to those in the nonadenomyosis group (aOR 1.86, 95% CI: 1.59-2.16). Results remained robust in the aforementioned several sensitivity analyses. CONCLUSIONS: This national-level analysis suggests that a diagnosis of uterine adenomyosis is associated with an increased risk of placental pathology (placenta accreta spectrum, placenta abruption, and placental previa) and adverse maternal outcomes at delivery.

Impact of lymphadenectomy in patients with locally recurrent or persistent cervical cancer treated with salvage hysterectomy.

AIM: To investigate the role of lymphadenectomy (LND) in locally recurrent or persistent cervical cancer patients treated with salvage hysterectomy. METHODS: Locally recurrent or persistent cervical cancer patients treated with salvage hysterectomy, with or without LND, were identified. Patients were divided into two groups according to the status of radiologic evidence of lymph node metastasis, and the impact of LND was investigated by evaluating postoperative survival. RESULTS: This study included 72 patients; 48 did not show radiological evidence of lymph node metastasis (Group 1) while 24 did (Group 2). Overall, the addition of LND to salvage hysterectomy resulted in increased postoperative complications. In Group 1, salvage hysterectomy plus LND resulted in the identification of five cases with false-negative lymph nodes (19.2%), but showed no advantage over salvage hysterectomy alone in terms of postoperative survival. In Group 2, all patients underwent LND, which resulted in the identification of eight cases with false-positive nodes (33.3%), and reasonably long postoperative survival. The estimated 3-year postoperative survival rate in this group was 39.7%. CONCLUSION: Including LND in salvage hysterectomy allows for precise lymph node staging but increases risk of postoperative complications. However, considering the inability to improve survival, LND should not be performed during salvage hysterectomy in patients without radiological evidence of lymph node metastasis. In patients with radiological evidence of lymph node metastasis, salvage hysterectomy plus LND can only be performed in those who understand the risk of postoperative complications and the limited evidence supporting its survival advantage.

Anti-lipolysis-stimulated lipoprotein receptor monoclonal antibody as a novel therapeutic agent for endometrial cancer.

BACKGROUND: Endometrial cancer (EC) is a common gynecologic malignancy and patients with advanced and recurrent EC have a poor prognosis. Although chemotherapy is administered for those patients, the efficacy of current chemotherapy is limited. Therefore, it is necessary to develop novel therapeutic agents for EC. In this study, we focused on lipolysis-stimulated lipoprotein receptor (LSR), a membrane protein highly expressed in EC cells, and developed a chimeric chicken-mouse anti-LSR monoclonal antibody (mAb). This study investigated the antitumor effect of an anti-LSR mAb and the function of LSR in EC. METHODS: We examined the expression of LSR in 228 patients with EC using immunohistochemistry and divided them into two groups: high-LSR (n = 153) and low-LSR groups (n = 75). We developed a novel anti-LSR mAb and assessed its antitumor activity in an EC cell xenograft mouse model. Pathway enrichment analysis was performed using protein expression data of EC samples. LSR-knockdown EC cell lines (HEC1 and HEC116) were generated by transfected with small interfering RNA and used for assays in vitro. RESULTS: High expression of LSR was associated with poor overall survival (hazard ratio: 3.53, 95% confidence interval: 1.35-9.24, p = 0.01), advanced stage disease (p = 0.045), deep myometrial invasion (p = 0.045), and distant metastasis (p < 0.01). In EC with deep myometrial invasion, matrix metalloproteinase (MMP) 2 was highly expressed along with LSR. Anti-LSR mAb significantly inhibited the tumor growth in EC cell xenograft mouse model (tumor volume, 407.1 mm3 versus 726.3 mm3, p = 0.019). Pathway enrichment analysis identified the mitogen-activated protein kinase (MAPK) pathway as a signaling pathway associated with LSR expression. Anti-LSR mAb suppressed the activity of MAPK in vivo. In vitro assays using EC cell lines demonstrated that LSR regulated cell proliferation, invasion, and migration through MAPK signaling, particularly MEK/ERK signaling and membrane-type 1 MMP (MT1-MMP) and MMP2. Moreover, ERK1/2-knockdown suppressed cell proliferation, invasion, migration, and the expression of MT1-MMP and MMP2. CONCLUSIONS: Our results suggest that LSR contributes to tumor growth, invasion, metastasis, and poor prognosis of EC through MAPK signaling. Anti-LSR mAb is a potential therapeutic agent for EC.

Gynecologic oncologists in surgery for placenta accreta spectrum: a survey for practice, experience, and interest.

OBJECTIVE: Surgery for placenta accreta spectrum is associated with significant maternal morbidity and mortality. The role of gynecologic oncologists in the surgical management of placenta accreta spectrum is currently under investigation. This study examined the practices, experiences, and interests of gynecologic oncologists in placenta accreta spectrum surgeries. METHODS: The intervention was an anonymous, cross-sectional, 20-question survey sent to 1084 members of the Society of Gynecologic Oncology in the USA. RESULTS: A total of 184 gynecologic oncologists responded to the survey (response rate 17.0%). Most participating gynecologic oncologists have been practicing for >10 years after fellowship (53.2%), practice in urban-teaching hospitals (84.8%) with delivery volumes ≥3000/year (54.3%), and have a multidisciplinary approach (82.5%). Three-quarters (78.7%) feel that the rate of placenta accreta spectrum is increasing over time. One-third (35.5%) perform ≥6 hysterectomies for placenta accreta spectrum yearly. Less than half (45.5%) practice conservative management. Approximately half are involved from the beginning of the case (49.7%) and perform the surgery in the main operating room (59.4%). Almost three-quarters (71.6%) have experienced surgical blood loss >5 L and one-third (36.6%) have experienced cases with blood loss >10 L. About half (50.3%) of participants are interested in placenta accreta spectrum surgery for future practice. Gynecologic oncologists engaging in a multidisciplinary approach are more likely to practice in an urban-teaching hospital, have higher surgical volume, be involved from the beginning of the case, and be interested in placenta accreta spectrum surgery. Those >10 years post-training and in the Southern US region are more likely to practice conservative management or delayed hysterectomy. CONCLUSION: This society-based cross-sectional survey suggests that gynecologic oncologists are actively involved in the surgical management of placenta accreta spectrum in the USA. Nearly half of gynecologic oncologists who responded to the survey expressed interest in surgery for placenta accreta spectrum.

Successful management of a pregnant woman of lower-limb arteriovenous malformation with chronic cardiac failure.

The clinical features of extracranial arteriovenous malformations (AVM) vary from stages I (quiescence) with few symptoms to IV (decompensation) with overt symptoms of cardiac failure. Although the maternal outcomes of pregnant women with extracranial AVM is understudied due to its rarity, previous studies suggested the difficulty in the management of recurrent hemorrhage due to AVM progression during perinatal period; thus, pregnant case of extracranial AVM complicated with cardiac failure were considered challenging. We have reported a woman of stage IV extracranial AVM in the right lower limb with a history of below-the-knee amputation, in which two pregnancies and vaginal deliveries under epidural anesthesia were managed successfully. Cardiac failure did not exacerbate throughout the gestational or postpartum periods. Ulceration gradually worsened, with no massive hemorrhage. It is ideal to assess abnormal vascularity, especially in the lower abdomen, vagina, and epidural and subdural spaces, through magnetic resonance imaging to ensure safe delivery.

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

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.

Trends, characteristics, and outcomes of conservative management for placenta percreta.

PURPOSE: To examine trends, characteristics, and outcomes of women with placenta percreta who had conservative management at cesarean delivery (CD) without hysterectomy. METHODS: This is a retrospective cohort study querying the National Inpatient Sample. The Study population was comprised of women with diagnosis of placenta percreta who underwent CD from 10/2015-12/2018. Characteristics and surgical outcome of women who had hysterectomy at time of CD were compared to those who did not (conservative management) in multivariable analysis. RESULTS: A total of 1055 cases were examined, of which 790 (74.9%) received hysterectomy at CD and the remaining 265 (25.1%) had conservative management without hysterectomy. During the study period, performance of hysterectomy at CD increased from 71.4% to 93.8% (P < 0.001). In multivariable analysis, more recent cases of CD for placenta percreta were less likely to have conservative management [adjusted-odds ratio (aOR) per year-quarter 0.93, 95% confidence interval (CI) 0.89-0.97]. In contrast, hospitals with small-medium bed capacity (aOR 1.72, 95% CI 1.18-2.51), non-urban teaching setting (aOR 1.76, 95% CI 1.14-2.70), and located in the Midwest (aOR 2.55, 95% CI 1.56-4.17) were more likely to offer conservative management at CD. Later gestational age was also associated with a higher likelihood of conservative management (median gestational age, 36 versus 34 weeks, P < 0.001). Women in the conservative management group experienced lower measured surgical morbidity during the admission compared to those in the cesarean hysterectomy group (47.2% versus 75.9%, aOR 0.35, 95% CI 0.26-0.48). CONCLUSION: The clinical practice for placenta percreta appears to be shifting to upfront hysterectomy at the time of CD.

Population incidence and characteristics of secondary breast cancer after uterine cancer: a competing risk analysis.

PURPOSE: To examine incidence and characteristics of women who developed secondary breast cancer after uterine cancer. METHODS: This is a population-based retrospective cohort study utilizing the National Cancer Institute's Surveillance, Epidemiology, and End Result Program from 1973 to 2013. Women with uterine cancer who did not have synchronous or a history of breast cancer were followed after their uterine cancer diagnosis (N = 236,561). A time-dependent competing risk analysis was performed to examine cumulative incidences and clinico-pathological characteristics of those who subsequently developed breast cancer. RESULTS: There were 7110 (3.0%) women who developed secondary breast cancers after uterine cancer with 5-, 10-, and 20-year cumulative incidence rates of 1.5, 2.8, and 4.7%, respectively. The increase in the rate of secondary breast cancer was particularly high in the first 3 years after a uterine cancer diagnosis (annual percent change [APC] 4.9), followed by 3-7 years (APC 1.6) after diagnosis (P < 0.001). The median time to develop secondary breast cancer was 6.4 years. Older women had significantly shorter time intervals between uterine and breast cancer diagnoses (3.7 years for aged > 71, 5.9 for aged 64-71, 7.6 for aged 56-63, and 9.4 for aged < 56, P < 0.001). In a multivariable analysis, older age, White race, married status, endometrioid, serous, and mixed histology types, and early-stage tumors remained as independent factors of developing secondary breast cancer (all, P < 0.05). CONCLUSION: Tumor factors with endometrioid and serous histology types and early-stage disease were the factors associated with secondary breast cancer after uterine cancer diagnosis. Older women had shorter time to develop secondary breast cancer.

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

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.

Primary Fallopian Tube Carcinoma Presenting with a Massive Inguinal Tumor: A Case Report and Literature Review.

Primary fallopian tube carcinoma (PFTC) has characteristics similar to those of ovarian carcinoma. The typical course of PFTC metastasis includes peritoneal dissemination and pelvic and paraaortic lymph node metastasis, while inguinal lymph node metastasis is rare. Moreover, the initial presentation of PFTC with an inguinal tumor is extremely rare. A 77-year-old postmenopausal woman presented with a massive 12-cm inguinal subcutaneous tumor. After tumor resection, histopathological and immunohistochemical analysis showed that the tumor was a high-grade serous carcinoma of gynecological origin. Subsequent surgery for total hysterectomy with bilateral salpingo-oophorectomy revealed that the tumor developed in the fallopian tube. She received adjuvant chemotherapy with carboplatin and paclitaxel, followed by maintenance therapy with niraparib. There has been no recurrence or metastasis 9 months after the second surgery. We reviewed the literature for cases of PFTC and ovarian carcinoma that initially presented with an inguinal tumor. In compliance with the Preferred Reporting Items for Systematic Reviews guidelines, a systematic literature search was performed through 31 January 2022 using the PubMed and Google scholar databases and identified 14 cases. In half of them, it was difficult to identify the primary site using preoperative imaging modalities. Disease recurrence occurred in two cases; thus, the prognosis of this type of PFTC appears to be good.

CD70 antibody-drug conjugate: A potential novel therapeutic agent for ovarian cancer.

This study aimed to investigate the cytotoxicity of a cluster of differentiation 70 antibody-drug conjugate (CD70-ADC) against ovarian cancer in in vitro and in vivo xenograft models. CD70 expression was assessed in clinical samples by immunohistochemical analysis. Western blotting and fluorescence-activated cell sorting analyses were used to determine CD70 expression in the ovarian cancer cell lines A2780 and SKOV3, and in the cisplatin-resistant ovarian cancer cell lines A2780cisR and SKOV3cisR. CD70 expression after cisplatin exposure was determined in A2780 cells transfected with mock- or nuclear factor (NF)-κB-p65-small interfering RNA. We developed an ADC with an anti-CD70 monoclonal antibody linked to monomethyl auristatin F and investigated its cytotoxic effect. We examined 63 ovarian cancer clinical samples; 43 (68.3%) of them expressed CD70. Among patients with advanced stage disease (n = 50), those who received neoadjuvant chemotherapy were more likely to exhibit high CD70 expression compared to those who did not (55.6% [15/27] vs 17.4% [4/23], P < .01). CD70 expression was confirmed in A2780cisR, SKOV3, and SKOV3cisR cells. Notably, CD70 expression was induced after cisplatin treatment in A2780 mock cells but not in A2780-NF-κB-p65-silenced cells. CD70-ADC was cytotoxic to A2780cisR, SKOV3, and SKOV3cisR cells, with IC50 values ranging from 0.104 to 0.341 nmol/L. In A2780cisR and SKOV3cisR xenograft models, tumor growth in CD70-ADC treated mice was significantly inhibited compared to that in the control-ADC treated mice (A2780cisR: 32.0 vs 1639.0 mm3 , P < .01; SKOV3cisR: 232.2 vs 584.9 mm3 , P < .01). Platinum treatment induced CD70 expression in ovarian cancer cells. CD70-ADC may have potential therapeutic implications in the treatment of CD70 expressing ovarian cancer.

Association Between Adjuvant Therapy and Survival in Stage II-III Endometrial Cancer: Influence of Malignant Peritoneal Cytology.

OBJECTIVE: The aim of this study was to examine the survival effect of adjuvant therapy in stage II-III endometrial cancer based on peritoneal cytology results. METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results Program was retrospectively queried to examine 7467 women with stage II-III endometrial cancer who underwent hysterectomy, and with available peritoneal cytology results, from 2010 to 2016. A Cox proportional hazard regression model was fitted to assess the association between adjuvant therapy and all-cause mortality stratified by peritoneal cytology results. RESULTS: Malignant peritoneal cytology was reported in 1662 (22.3%) women and was associated with non-endometrioid histology, higher tumor stage, and nodal metastasis (p < 0.05). In a propensity score-weighted model, malignant peritoneal cytology was associated with increased all-cause mortality compared with negative peritoneal cytology (hazard ratio 1.35, 95% confidence interval 1.23-1.48). Adjuvant therapy types varied based on histology and peritoneal cytology results. In non-endometrioid histology, the combination of chemotherapy and whole pelvic radiotherapy (WPRT) was associated with improved overall survival compared with chemotherapy or WPRT alone irrespective of the peritoneal cytology results (p < 0.05). The combination of chemotherapy and WPRT was also associated with improved overall survival in women with endometrioid histology and malignant peritoneal cytology (p = 0.026). Women with endometrioid histology and negative peritoneal cytology represented the most common subpopulation (46.5%), and overall survival was similar regardless of which of the three adjuvant therapy modalities was used (p = 0.319). CONCLUSIONS: Malignant peritoneal cytology is prevalent and prognostic in stage II-III endometrial cancer. This study found that the surgeon's choice and benefit of adjuvant therapy for women with stage II-III endometrial cancer differed depending on the status of peritoneal cytology.

Significance of Malignant Peritoneal Cytology on Survival of Women with Uterine Sarcoma.

PURPOSE: This study was designed to examine the association between malignant peritoneal cytology and survival of women with uterine sarcoma. METHODS: This retrospective, observational study queried the National Cancer Institute's Surveillance, Epidemiology, and End Result Program. Uterine sarcoma cases diagnosed from 2010 to 2016 with known peritoneal cytology results were examined. Propensity score inverse probability of treatment weighting was fitted to balance the measured covariates. Overall survival (OS) was compared between malignant and negative cytology cases. RESULTS: A total of 1481 uterine sarcomas were examined. Malignant peritoneal cytology was seen in 146 (9.9%) cases. Women who had T3 disease and distant metastases had the highest incidence of malignant peritoneal cytology (43.1%). In multivariable analysis, higher T stage, nodal involvement, distant metastasis, poorer tumor differentiation, and rhabdomyosarcoma/endometrial stromal sarcoma were significantly associated with an increased risk of malignant peritoneal cytology (all, P < 0.05). In the weighted model, malignant peritoneal cytology was associated with a nearly twofold increased risk of all-cause mortality compared with negative peritoneal cytology (3-year OS rate 34.7% versus 60.2%; hazard ratio 2.26; 95% confidence interval 1.88-2.71; P < 0.001). The absolute difference in the 3-year survival rate was particularly large in leiomyosarcoma (3-year OS rate 2.8% versus 51.9%; hazard ratio 2.64; 95% confidence interval 1.94-3.59; P < 0.001). Malignant peritoneal cytology was also associated with an increased all-cause mortality risk in early and advanced stages (both, P < 0.05). CONCLUSIONS: Our study suggests that malignant peritoneal cytology may be a prognostic factor for increased mortality in uterine sarcoma, particularly in uterine leiomyosarcoma.

PD-1+ Tim3+ tumor-infiltrating CD8 T cells sustain the potential for IFN-γ production, but lose cytotoxic activity in ovarian cancer.

Persistent exposure to tumor antigens results in exhausted tumor-infiltrating T cells (TILs) that express the immune checkpoint molecules, PD-1 and Tim3, and lack anti-tumor immunity. To examine the exhausted status of TILs in ovarian cancer, the potential for cytokine production, proliferation and cytotoxicity by purified PD-1+ Tim3+ CD8 TILs was assessed. The production of IFN-γ and TNF-α by PD-1+ Tim3+ CD8 TILs remained the same in an intracellular cytokine staining assay and was higher in a cytokine catch assay than that by PD-1- Tim3- and PD-1+ Tim3- CD8 TILs. %Ki67+ was higher in PD-1+ Tim3+ CD8 TILs than in PD-1- Tim3- CD8 TILs. However, patients with high PD-1+ Tim3+ CD8 TILs had a poor prognosis. The potential for cytotoxicity was then examined. %Perforin+ and %granzyme B+ were lower in PD-1+ Tim3+ CD8 TILs than in PD-1- Tim3- and PD-1+ Tim3- CD8 TILs. To observe the potential for direct cytotoxicity by T cells, a target cell line expressing membrane-bound anti-CD3scFv was newly established and a cytotoxic assay targeting these cells was performed. The cytotoxicity of PD-1+ Tim3+ CD8 TILs was significantly lower than that of PD-1- Tim3- and PD-1+ Tim3- CD8 TILs. Even though PD-1+ Tim3+ CD8 TILs in ovarian cancer showed a sustained potential for cytokine production and proliferation, cytotoxicity was markedly impaired, which may contribute to the poor prognosis of patients with ovarian cancer. Among the impaired functions of exhausted TILs, cytotoxicity may be an essential target for cancer immunotherapy.

Surgical and oncologic outcomes of hyperthermic intraperitoneal chemotherapy for uterine leiomyosarcoma: A systematic review of literature.

OBJECTIVE: To examine the perioperative and survival outcomes in women with disseminated peritoneal uterine leiomyosarcoma (uLMS) who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: A comprehensive systematic review of literature was conducted using multiple public search engines, PubMed, Scopus, and the Cochrane Library, in compliance with the PRISMA guidelines. Women with disseminated peritoneal uLMS treated with CRS-HIPEC were analyzed. Perioperative morbidity and mortality rate as well as oncologic outcomes related to CRS-HIPEC were assessed. RESULTS: Ten studies met the inclusion criteria from 2004 to 2020, including 8 case series (n=28) and 2 original articles (n=47). Of the 75 patients, 68 (90.7%) were women with uLMS whereas 7 women were non-uLMS. Of these, 64 (85.3%) had recurrent disease, and 39 (52.0%) received chemotherapy or radiotherapy prior to CRS-HIPEC. The perioperative mortality rate was 4.0% (intraoperative 1.3%, and postoperative 2.7%), and postoperative complications (grade ≥3) rate ranged 21.4-22.2%. With regard to HIPEC regimens (n=75), cisplatin was most frequently used (n=55, 73.3%) followed by melphalan (n=17, 22.7%) and others (n=3, 4.0%). Among the two observational studies, the median overall survival after CRS-HIPEC treatment was 29.5-37 months. In one limited comparative effectiveness study (n=13), albeit statistically non-significant CRS-HIPEC was associated with higher progression-free survival versus CRS alone (3-year rates, 71.4% versus 0%, P=0.10). When the HIPEC regimens were compared, melphalan use was associated with decreased uLMS-related mortality compared to a cisplatin-based regimen, but the association was not statistically significant (hazard ratio 0.35, 95% confidence interval 0.04-3.05, P=0.35). CONCLUSION: Effectiveness of CRS-HIPEC for disseminated peritoneal uLMS is yet to be determined. As interpretation of the available data on survival is limited due to small sample sizes or the lack of an active comparator, further study is warranted to examine the safety and survival effect of CRS-HIPEC in disseminated peritoneal uLMS.