Accuracy of Shunt Volume Measured by Three-Dimensional Echocardiography and Cardiac Magnetic Resonance in Patients with an Atrial Septal Defect and a Dilated Right Ventricle.

BACKGROUND: The accuracy of right ventricular (RV) quantification by three-dimensional echocardiography (3DE) has been reported mainly in patients with a normal RV. However, there are no data regarding the accuracy of 3DE in patients with a dilated RV, as in shunt diseases. In this study, we evaluated the accuracy of 3DE and that of volumetric cardiac magnetic resonance (CMR) for assessment of RV and left ventricular (LV) stroke volume (SV) and the pulmonary (Qp)/systemic (Qs) blood flow ratio in patients with an atrial septal defect (ASD) using the two-dimensional phase contrast (2DPC) method as the gold standard. METHODS: We retrospectively investigated 83 patients with ASD who underwent transcatheter closure and clinically indicated CMR and 3DE examinations. Qp/Qs was calculated using RV and LV SV measured by full-volume volumetric 3DE (Vol-3DE) and CMR (Vol-CMR) and by two-dimensional pulse Doppler quantification (2D-Dop); the parameters were compared using 2DPC-CMR as the gold standard. RESULTS: There was no significant difference in the Qp/Qs value between 2DPC-CMR and Vol-3DE (2.29 ± 0.70 vs. 2.21 ± 0.63, P=0.79) and 2D-Dop (vs. 2.21 ± 0.65, P=1.00); however, a significant difference was found between 2DPC-CMR and Vol-CMR (P<0.001). The Qp/Qs value obtained using Vol-3DE showed the best correlation with 2DPC-CMR (r=0.93, P<0.001). The RV and LV SV values obtained by Vol-3DE showed the best correlation with 2DPC-CMR (RV SV, r=0.82, P<0.001; LV SV, r=0.73, P<0.001), although the absolute values were underestimated. CONCLUSION: Qp/Qs was more accurately evaluated by Vol-3DE than by Vol-CMR or 2D-Dop. 3DE assessment was feasible and reproducible even in a dilated RV.

Evaluation of thyroid congestion in patients with heart failure using shear wave elastography: An observational study.

Shear wave elastography (SWE) is a noninvasive method for measuring organ stiffness. Liver stiffness measured using SWE reflects hepatic congestion in patients with heart failure (HF). However, little is known about the use of SWE to assess other organ congestions. This study aimed to evaluate the utility of SWE for assessing not only the liver but also thyroid congestion in patients with HF. This prospective study included 21 patients with HF who have normal thyroid lobes (age: 77.0 ±â€…11.0, men: 14). Thyroid and liver stiffness were measured by SWE using the ARIETTA 850 ultrasonography system (Fujifilm Ltd., Tokyo, Japan). SWE of the thyroid was performed on B-mode ultrasonography; a target region was identified within a region of interest. SWE was performed in each lobe of the thyroid gland. Five measurements were taken at the same location and the averages were recorded for comparison. We investigated the relationship between SWE for evaluating thyroid stiffness and the clinical characteristics of patients with HF. SWE of the thyroid was significantly correlated with SWE of the liver (R = 0.768, P < .001), thyroid stimulation hormone (R = 0.570, P = .011), free thyroxine (R = 0.493, P = .032), estimated right atrial pressure (RAP; R = 0.468, P = .033), and composite congestion score (R = 0.441, P = .045). SWE may be useful for evaluating thyroid stiffness and assessing the degree of thyroid congestion. Thyroid congestion may reflect the elevation of RAP and cause thyroid dysfunction through organ congestion.

Cardiac Reversibility and Survival After Transcatheter Aortic Valve Implantation in Patients With Low-Gradient Aortic Stenosis.

Background Prognostic implications of transcatheter aortic valve implantation (TAVI) in low-gradient (LG) aortic stenosis (AS) remain controversial. The authors hypothesized that differences in cardiac functional recovery may solve this ongoing controversy. The aim was to evaluate clinical outcomes and the response of left ventricular (LV) function following TAVI in patients with LG AS. Methods and Results This multicenter retrospective study included 1742 patients with severe AS undergoing TAVI between January 2015 and March 2019. Patients were subdivided into low-flow (LF) LG, normal-flow (NF) LG, LF high-gradient, and NF high-gradient AS groups according to the mean gradient of the aortic valve (LG <40 mm Hg) and LV stroke volume index (LF <35 mL/m2). Outcomes and changes in echocardiographic parameters after TAVI were compared between the groups. A total of 227 patients (13%) had reduced ejection fraction, and 486 patients (28%) had LG AS (LF-LG 143 [8%]; NF-LG 343 [20%]). During a median follow-up period of 747 days, 301 patients experienced a composite end point of cardiovascular death and rehospitalization for cardiovascular events, which was higher in the LF-LG and NF-LG groups than in the high-gradient groups. LG AS was independently associated with the primary outcome (hazard ratio, 1.69; P<0.001). Among 1239 patients with follow-up echocardiography, LG AS showed less improvement in the LV mass index and LV end-diastolic volume compared with high-gradient AS after 1 year, while LV recovery was similar between the LF AS and NF AS groups. Conclusions LG AS was associated with poorer outcomes and LV recovery, regardless of flow status after TAVI. Careful evaluation of AS severity may be required in LG AS to provide TAVI within the appropriate time and advanced care afterward.

Factors Influencing Acceptance of the Chairperson Position at Annual Scientific Meetings of the Japanese Circulation Society　- A Questionnaire Survey in Chugoku District.

Background: The Japanese Circulation Society survey revealed that Japanese female cardiologists exhibited a trend to refuse the chairperson position; however, the causal factors remain uncertain. Methods and Results: We distributed a questionnaire survey among chairpersons of the Chugoku regional meeting in November 2022. The rate of chair acceptance at the annual meeting tended to increase as the chairperson's experience grew (first time chairing a meeting, 25.0%; 2-3 times, 33.3%; 4-5 times, 53.8%; ≥6 times, 70.0%; P=0.021). Conclusions: Providing inexperienced members with the chance to perform the role of chairperson will lead to them accepting to chair annual meetings.

Increased Floral Rewards due to Local Adaptation Drives Plant Ecological Speciation via Learned Preferences of Pollinators.

AbstractIn animal-pollinated plants, the growth environment and pollination environment are two important agents of natural selection. However, their simultaneous effects on plant speciation remain underexplored. Here, we report a theoretical finding that if plants' local adaptation to the growth environment increases their floral rewards for pollinators, it can strongly facilitate ecological speciation in plants. We consider two evolving plant traits, vegetative and floral signal traits, in a population genetic model for two plant populations under divergent selection from different growth environments. The vegetative trait determines plants' local adaptation. Locally adapted plants reward pollinators better than maladapted plants. By associative learning, pollinators acquire learned preferences for floral signal traits expressed by better-rewarding plants. If pollinators' learned preferences become divergent between populations, floral signal divergence occurs and plants develop genetic associations between vegetative and floral signal traits, leading to ecological speciation via a two-allele mechanism. Interestingly, speciation is contingent on whether novel floral signal variants arise before or after plant populations become locally adapted to the growth environment. Our results suggest that simultaneous selection from growth and pollination environments might be important for the ecological speciation of animal-pollinated plants.

Gallbladder Wall Thickness-Based Assessment of Organ Congestion in Patients With Heart Failure.

Background: Diffuse gallbladder (GB) wall thickening is caused by elevated systemic venous pressure, such as heart failure (HF). This study investigated the relationship between GB wall thickness (WT) and HF, and the prognostic impact of GBWT. Methods and Results: This prospective study included 116 patients with HF and 11 healthy controls. Among the 116 patients, 30 with GBWT measurements in the postprandial state or a history and/or signs of GB disease were excluded. The remaining 86 patients had significantly higher GBWT than the controls (median [interquartile range {IQR}] 2.0 [1.7-2.4] vs. 1.3 [1.1-1.6] mm, respectively; P<0.001). GBWT was significantly correlated with B-type natriuretic peptide (r=0.386, P<0.001), left atrial volume index (r=0.452, P<0.001), and tricuspid annular plane systolic excursion (r=-0.311, P=0.006). GBWT also exhibited a stepwise increasing relationship with increasing HF stage (Stage B, 22 patients, median [IQR] 1.8 [1.7-2.1] mm; Stage C, 60 patients, 2.0 [1.8-2.5] mm; and Stage D, 4 patients: 4.0 [3.5-4.5] mm). In Stage C or D HF patients, 11 hospitalizations for HF were observed over a median follow-up of 303 days (IQR 125-394 days). Furthermore, the rate of hospitalization events for HF was significantly higher in the high (≥3 mm) than low GBWT group (P=0.007). Conclusions: GBWT can be used to assess organ congestion in patients with HF.

Negative-Pressure Pulmonary Edema and Takotsubo Cardiomyopathy in the Older Adults.

Negative-pressure pulmonary edema (NPPE) is a non-cardiogenic pulmonary edema caused by a sudden drop in the intrathoracic pressure associated with upper airway obstruction. Takotsubo cardiomyopathy (TCM) can often be triggered by intense stress and is more common in older women. In this case report, we describe a case of NPPE associated with upper airway obstruction and TCM associated with stress by upper airway obstruction in an 85-year-old woman. When encountering pulmonary edema associated with upper airway obstruction in older adults, the possibility of NPPE and TCM complications should be considered.

Combinational Elastography.

Heart failure (HF) can cause liver congestion and stiffness. Elastography is used to noninvasively measure organ stiffness. Liver fibrosis (LF) is monitored by shear wave and strain elastography. However, shear wave velocity (Vs) on shear wave elastography varies under the influence of fibrosis and congestion, and the LF index by strain elastography reflects only LF progression. Little is known about the usefulness of these methods in HF patients. This prospective study evaluated combined shear wave and strain elastography (i.e., combinational elastography) for assessing liver congestion. A total of 51 patients with HF (33 outpatients and 18 inpatients) and 10 healthy participants were included. Further, the relationships between combinational elastography and clinical characteristics in 51 patients with HF and the effects of medical treatment on these relationships in 18 inpatients with HF were investigated. Vs was significantly higher in the HF group than in the control group (1.68 ± 0.47 versus 1.21 ± 0.16, P = 0.002). The LF index did not significantly differ (1.39 ± 0.40 versus 1.33 ± 0.15, P = 0.680). Vs decreased after treatment (from 2.01 ± 0.61 to 1.62 ± 0.49 m/seconds; P = 0.026), while the LF index did not change (from 1.21 ± 0.29 to 1.26 ± 0.27; P = 0.664). Brain natriuretic peptide level (r = 0.343; P = 0.003) and composite congestion scores (r = 0.455; P < 0.001) were correlated with Vs. Combinational elastography is useful for assessing liver congestion, differentiating between liver congestion and fibrosis, and assessing therapeutic effects in HF patients.

[Gantry QA Using Three-dimensional Diode Array Detector on O-ring Linear Accelerator].

PURPOSE: It is necessary to perform gantry quality assurance (QA) in high precision radiotherapy. However, the O-ring type linear accelerator (Halcyon) does not have a light field and laser as a reference of isocenter point. The aim of this study is to investigate the usefulness of a three-dimensional diode array detector for gantry angle QA, and an O-ring type linear accelerator. METHOD: The gantry angle and rotational center were verified using the ArcCHECK 3D diode array on the general linear accelerator (TrueBeam) as a reference and Halcyon. The gantry angles were measured at 0, 90, 180, and 270°. The accuracy of the gantry rotational center was evaluated using rotational irradiation in the clockwise and counterclockwise directions between 181° and 179°. RESULTS: The QA system with ArcCHECK was able to apply on the TrueBeam and Halcyon. As a result of the accuracy of the gantry angle, the maximum error of value calculated from ArcCHECK was 0.1° compared with the nominal gantry angle of Halcyon. As a result of the accuracy of the gantry rotation isocenter of Halcyon, the distance between the isocenter and the gantry rotation center was 0.45 mm and 0.41 mm in the clockwise and counterclockwise directions, respectively. CONCLUSION: The QA system with ArcCHECK was useful for the gantry angle and the rotation center accuracy on the Halcyon.

Functional Innovation through Gene Duplication Followed by Frameshift Mutation.

In his influential book "Evolution by Gene Duplication", Ohno postulated that frameshift mutation could lead to a new function after duplication, but frameshift mutation is generally thought to be deleterious, and thus drew little attention in functional innovation in duplicate evolution. To this end, we here report an exhaustive survey of the genomes of human, mouse, zebrafish, and fruit fly. We identified 80 duplicate genes that involved frameshift mutations after duplication. The frameshift mutation preferentially located close to the C-terminus in most cases (55/88), which indicated that a frameshift mutation that changed the reading frame in a small part at the end of a duplicate may likely have contributed to adaptive evolution (e.g., human genes NOTCH2NL and ARHGAP11B) otherwise too deleterious to survive. A few cases (11/80) involved multiple frameshift mutations, exhibiting various patterns of modifications of the reading frame. Functionality of duplicate genes involving frameshift mutations was confirmed by sequence characteristics and expression profile, suggesting a potential role of frameshift mutation in creating functional novelty. We thus showed that genomes have non-negligible numbers of genes that have experienced frameshift mutations following gene duplication. Our results demonstrated the potential importance of frameshift mutations in molecular evolution, as Ohno verbally argued 50 years ago.

Current Diversity Issues in Cardiovascular Workplaces in the Chugoku District　- Results From 2 Questionnaire Surveys.

Background: Various issues, such as gender diversity and overwork, need to be considered in cardiovascular workplaces. Here, we report the results of 2 questionnaire surveys conducted among members of the Chugoku branch of the Japanese Circulation Society. Methods and Results: The first questionnaire was posted to all 194 female members in 2018. Of the 73 respondents, 61.6% reported feeling that it would be difficult to continue in cardiovascular care. The second questionnaire was completed by participants of the Chugoku Regional Meeting in 2019. Of the 133 respondents, 42.4% reported difficulties continuing in cardiovascular care. Respondents reporting difficulties had a significantly lower mean age, a higher frequency of day and night shifts, and a higher rate of working >80 h/week than respondents who did not report such difficulties. In logistic regression analysis, working >80 h/week was the only independent factor associated with difficulties continuing in cardiovascular care (odds ratio 4.16; 95% confidence interval 1.46-11.9; P=0.008). Although 47.4% of respondents worked >960 h overtime per year (considered a risk factor for death from overwork), 59.6% of these respondents reported being satisfied with their current situation. Conclusions: In the Chugoku region, the work-life balance of medical personnel engaged in cardiovascular care has not been sufficiently secured. In order to promote diverse human resources, we need to recognize the current situation and continue to take countermeasures.

Assessment of organ congestion in patients with heart failure by ultrasonography.

In recent years, there has been a growing interest in assessing congestion of organs (e.g., liver, kidneys, lungs, intestines) in patients with heart failure (HF). HF involves an increased risk of mortality, thereby making it important to evaluate organ congestion. Ultrasonography is a useful tool for noninvasive and repeatable evaluation of patients with HF. Noninvasive evaluation of organ congestion can also be used to assess hemodynamics. It may further be useful for elucidating organ cross-talk in patients with HF. This review discusses the clinical implications of evaluating organ congestion by ultrasonography.

Muller's ratchet of the Y chromosome with gene conversion.

Muller's ratchet is a process in which deleterious mutations are fixed irreversibly in the absence of recombination. The degeneration of the Y chromosome, and the gradual loss of its genes, can be explained by Muller's ratchet. However, most theories consider single-copy genes, and may not be applicable to Y chromosomes, which have a number of duplicated genes in many species, which are probably undergoing concerted evolution by gene conversion. We developed a model of Muller's ratchet to explore the evolution of the Y chromosome. The model assumes a nonrecombining chromosome with both single-copy and duplicated genes. We used analytical and simulation approaches to obtain the rate of gene loss in this model, with special attention to the role of gene conversion. Homogenization by gene conversion makes both duplicated copies either mutated or intact. The former promotes the ratchet, and the latter retards, and we ask which of these counteracting forces dominates under which conditions. We found that the effect of gene conversion is complex, and depends upon the fitness effect of gene duplication. When duplication has no effect on fitness, gene conversion accelerates the ratchet of both single-copy and duplicated genes. If duplication has an additive fitness effect, the ratchet of single-copy genes is accelerated by gene duplication, regardless of the gene conversion rate, whereas gene conversion slows the degeneration of duplicated genes. Our results suggest that the evolution of the Y chromosome involves several parameters, including the fitness effect of gene duplication by increasing dosage and gene conversion rate.

Prognostic similarity between ovarian mucinous carcinoma with expansile invasion and ovarian mucinous borderline tumor: A retrospective analysis.

ABSTRACT: There is a similarity of histological features and survival between ovarian mucinous carcinoma (MC) with expansile invasion and ovarian mucinous borderline tumor (MBT). The aim of this study was to compare the clinical outcomes of MC with expansile invasion with those of MBT based on the 2020 World Health Organization (WHO) criteria.A pathological review was performed on patients with MC, ovarian MBT, and seromucinous borderline tumors that underwent surgery at our hospital between 1984 and 2019. Clinicopathological features were compared retrospectively between MC with expansile invasion and MBT.Among 83 cases of MC, 85 cases of MBT, and 12 cases of seromucinous borderline tumor, 25 MC cases with expansile invasion and 98 MBT cases were included through review. MC cases with expansile invasion were diagnosed with advanced International Federation of Gynecology and Obstetrics (FIGO) stages more frequently (P = .02) than that of MBT cases. In addition, patients with MC with expansile invasion received adjuvant chemotherapy more often (P < .01) than that of patients with MBT. There were no statistically significant differences in recurrence rate (P = .10) between MC with expansile invasion and MBT. Progression-free survival (PFS) was worse in MC cases with expansile invasion than that in MBT cases (P = .01). However, a multivariate analysis for PFS showed that histological subtype, FIGO stage, and adjuvant chemotherapy were not an independent prognostic factor.The prognostic outcome of MC with expansile invasion might mimic those of MBT. These results showed ovarian borderline tumor treatment could be applied to MC treatment.

Psoas muscle index at the fifth lumbar vertebra as a predictor of survival in epithelial ovarian cancers.

Almost a quarter of a century has passed since the term sarcopenia was defined. Sarcopenia is recognized as a poor prognostic factor in a variety of cancer types. In ovarian cancer, it remains controversial whether sarcopenia affects prognosis and how it should be evaluated. The present study aimed to evaluate the association between the volume of the psoas major muscle and survival in patients with epithelial ovarian cancer. Medical charts of patients with epithelial ovarian cancer who received first-line chemotherapy with paclitaxel and carboplatin at the National Defense Medical College Hospital (Tokorozawa, Japan) between April 2010 and January 2015 were retrospectively reviewed. The bilateral psoas major muscle areas at the fifth lumbar vertebra were measured using computed tomography images. The Institutional Review Board at National Defense Medical College Hospital (Tokorozawa, Japan) approved the study protocol. A total of 72 patients with epithelial ovarian cancer who received combination therapy with paclitaxel and carboplatin were identified and enrolled. The median psoas muscle index (PMI; psoas muscle major cross-sectional area divided by height squared) was 5.4 cm2/m2 (range, 3.3-10.0). Patients with higher PMI had significantly improved overall survival (OS) compared with those with lower PMI [log-rank test P=0.014; hazard ratio (HR), 2.61; 95% confidence interval (CI), 1.21-6.06]. Multivariate analysis for OS revealed that lower PMI was an independent unfavorable prognostic factor (HR, 3.87; 95% CI, 1.37-12.1; P=0.0098). The volume of psoas major muscle mass could be a potential biomarker for prognosis in patients with epithelial ovarian cancer.

Significance of mesothelin and CA125 expression in endometrial carcinoma: a retrospective analysis.

BACKGROUND: This study aimed to investigate the association between clinicopathologic factors, mesothelin, and cancer antigen (CA) 125 in endometrial carcinoma. METHODS: Between 1989 and 2017, patients with endometrial carcinoma who underwent total hysterectomy and bilateral salpingo-oophorectomy at our hospital were identified. The association between either or both immunochemical expression of mesothelin and CA125 and clinicopathological features were retrospectively examined. RESULTS: Among 485 patients, 171 were positive for mesothelin, 368 were positive for CA125, and 167 were positive for mesothelin and CA125. The expression of mesothelin and CA125 was positively correlated (p < 0.01). More patients with mesothelin expression showed myometrial invasion of more than 50% (p = 0.028) and positive lymphovascular invasion (p = 0.027). Similarly, more patients with co-expression of mesothelin and CA125 had myometrial invasion of more than 50% (p = 0.016) and positive lymphovascular invasion (p = 0.02). Patients with mesothelin expression and co-expression of mesothelin and CA125 demonstrated worse progression-free survival (PFS) and overall survival (OS). In the multivariate analysis, mesothelin expression and co-expression were poor prognostic factors for PFS (mesothelin expression: hazard ratio [HR] = 2.14, p < 0.01; co-expression: HR = 2.19, p < 0.01) and OS (mesothelin expression: HR = 2.18, p < 0.01; co-expression: HR = 2.22, p < 0.01). CONCLUSIONS: Mesothelin expression and co-expression might be associated with tumor aggressiveness and poor prognosis in patients with endometrial carcinoma. Persons with mesothelin-expressing endometrial cancers present a particularly high medical unmet need.

Diagnostic efficacy of ascites cell block for ovarian clear cell carcinoma.

BACKGROUND: Ascites cytology is important for determining the stage and treatment methods for ovarian clear cell carcinoma (CCC) as defined by the 2014 International Federation of Obstetrics and Gynecology classification. METHODS: Patients with CCC who underwent surgery at our hospital between January 2012 and December 2019 and who received cytodiagnosis of their ascites using Papanicolaou (Pap) and May-Grünwald-Giemsa (MGG) staining, and cell block methods were identified. The cell block technique was performed using hematoxylin-eosin (H&E) staining and immunohistochemical staining for hepatocyte nuclear factor-1ß (HNF-1ß), estrogen receptor (ER), progesterone receptor (PR), and Wilms tumor-1 (WT-1). Cancer cells of CCC were defined as tumor cells that were positive for HNF-1ß and negative for ER, PR, and WT-1. The diagnostic accuracy of ascites cytology using Pap and MGG staining and cell block methods was examined. RESULTS: Based on cytological data, our study included 17 patients: seven (41.1%) with malignant (MAL) ascites, eight (47.1%) with negative for malignancy (NFM), and two (11.8%) with atypia of undetermined significance (AUS) because of a few atypical cells based on Pap and MGG staining. Malignant cells diagnosed by cell blocks were detected in 7/7 patients with MAL ascites based on PAP and MGG staining, 2/8 (25.0%) patients with NFM, and 1/2 (50%) patients with AUS. CONCLUSION: These findings show that the cell block method combined with the immunohistochemical investigation may be useful for increasing the diagnostic accuracy of malignant cells in CCC.

Multi-dimensional diffusion process of allele frequencies in population genetics.

One of the ultimate goals of population genetics is to theoretically describe the behavior of allele frequency. Diffusion theory has been commonly used for this purpose mainly in one-locus one-population models, although it is not easy to handle diffusion theory in models with multiple loci or with multiple populations. This review introduces several successful cases, where multi-dimensional diffusion equations contributed to addressing evolutionary questions, thereby demonstrating its strong potential in population genetics.

Criteria for placenta accreta spectrum in the International Federation of Gynaecology and Obstetrics classification, and topographic invasion area are associated with massive hemorrhage in patients with placenta previa.

INTRODUCTION: Placenta previa with placenta accreta spectrum (PAS) is a life-threatening disease that results in massive hemorrhage. The clinical and histologic criteria of PAS were adopted according to the International Federation of Gynaecology and Obstetrics (FIGO) classification. We aimed to investigate whether FIGO criteria and topography were associated with maternal complications in patients with placenta previa. MATERIAL AND METHODS: Patients with placenta previa who underwent cesarean section at our institution between January 2003 and December 2019 were identified. First, they were divided based on FIGO classification, as follows: Group A, with clinical criteria; Group B, with histologic criteria; and Group C: without clinical or histologic criteria. Next, cases with PAS were classified according to the topographic invasion area, as follows: type 1, upper posterior bladder; type 2, lower posterior bladder; type 3, parametrium; type 4, posterior lower uterine segment. Predictive factors for massive hemorrhage were retrospectively analyzed. RESULTS: Among the 350 patients, 24 (6.9%) were classified as Group A, 16 (4.6%) as Group B and 310 (88.5%) as Group C. Regarding maternal history and hemostatic procedures, there were no significant factors other than hysterectomy (p < .01) in Groups A and B. The volume of blood loss in both Groups A and B was greater than in Group C (p < .01). The rates of uterine artery embolization and blood transfusion were higher in Groups A and B than in Group C (p < .01). In addition, there were no significant factors other than hysterectomy between Groups A and B. In the multivariate analysis for massive hemorrhage, Group A (odds ratio: 2.73, p = .04) and Group B (odds ratio: 12.69, p < .01) were identified as independent predictive factors. In addition, massive hemorrhage was closely related to the lower posterior bladder and parametrial invasion in both Groups A and B. CONCLUSIONS: Both clinical and histologic criteria for PAS in the FIGO classification were associated with massive hemorrhage. Diagnosing clinical PAS using the FIGO classification, additional hemostatic procedures might be necessary according to the topographic invasion area.