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To examine whether artificial intelligence can achieve discoveries regarding fetal brain activity.In this observational study, the authors collected images of fetal faces using a four-dimensional ultrasound technique obtained from singleton pregnancies of outpatients in routine practice at 27 to 37 weeks of gestation between February 1 and December 31, 2021. The authors developed an artificial intelligence classifier to recognize seven facial expressions of fetuses, then applied it to video files of fetal facial images to generate the probabilities, as confidence scores, of each expression category. Discrete Fourier transform and chaotic analysis were used to investigate the scores. Mann-Whitney test, t test, variance test, and one-way analysis of variance were used for statistical analysis.Facial expression changes were observed in cycles averaging 66 to 73 s. The power spectrum showed that mouthing and neutral expressions were the most prevalent. There was a difference between categories for the spectrum (p = 0.004). Two different states--dense and sparse--of confidence scores were discovered. The correlation dimension was 1.19 ± 0.22 and 1.33 ± 0.27 for dense and sparse, respectively (p = 0.047).This method objectively and quantitatively demonstrated fetal brain activity and may provide insight into how the fetus spends its time in utero.

Objectives To study whether the free energy principle can explain fetal brain activity and the existence of fetal consciousness via a chaotic dimension derived using artificial intelligence. Methods In this observational study, we used a four-dimensional ultrasound technique obtained to collect images of fetal faces from pregnancies at 27–37 weeks of gestation, between February and December 2021. We developed an artificial intelligence classifier that recognizes fetal facial expressions, which are thought to relate to fetal brain activity. We then applied the classifier to video files of facial images to generate each expression category’s probabilities. We calculated the chaotic dimensions from the probability lists, and we created and investigated the free energy principle’s mathematical model that was assumed to be linked to the chaotic dimension. We used a Mann–Whitney test, linear regression test, and one-way analysis of variance for statistical analysis. Results The chaotic dimension revealed that the fetus had dense and sparse states of brain activity, which fluctuated at a statistically significant level. The chaotic dimension and free energy were larger in the sparse state than in the dense state. Conclusions The fluctuating free energy suggests consciousness seemed to exist in the fetus after 27 weeks.

Objectives To assess fetal cardiac structures using HDlive Flow Silhouette with spatiotemporal image correlation (STIC) at 12 to 14 + 6 weeks of gestation, and verify the feasibility of obtaining five cardiac views in the late first and early second trimesters of pregnancy. The fetal cardiac shape and the aspect of the descending aorta were also evaluated. Methods Eighty normal fetuses at 12 to 14 + 6 weeks of gestation were studied using trans-abdominal HDlive Flow Silhouette with STIC to assess the feasibility of five fetal cardiac views (frontal, spatial three-vessel, panoramic, posterior, and right lateral views). Target structures in each cardiac view were evaluated. ‘Good’ was assigned when all structures were noted, ‘Fair’ when only one structure was missed, and ‘Poor’ when two and more structures could not be detected. Frequencies of an elongated heart and those of a tortuous descending aorta were counted. Results Forty-nine fetuses were effectively included in the analysis. Success rates of ‘Good’ and ‘Fair’ were significantly higher with spatial three-vessel (p Conclusions The feasibility of obtaining fetal five cardiac views using HDlive Flow Silhouette with STIC is good, and this technique provides useful information for evaluating fetal cardiac structures in the late first and early second trimesters of pregnancy.

Predicting a live birth by artificial intelligence incorporating both the blastocyst image and conventional embryo evaluation parameters

Purpose To identify artificial intelligence (AI) classifiers in images of blastocysts to predict the probability of achieving a live birth in patients classified by age. Results are compared to those obtained by conventional embryo (CE) evaluation. Methods A total of 5691 blastocysts were retrospectively enrolled. Images captured 115 hours after insemination (or 139 hours if not yet large enough) were classified according to maternal age as follows

Purpose To make the artificial intelligence (AI) classifiers of the image of the blastocyst implanted later in order to predict the probability of achieving live birth. Methods A system for using the machine learning approaches, which are logistic regression, naive Bayes, nearest neighbors, random forest, neural network, and support vector machine, of artificial intelligence to predict the probability of live birth from a blastocyst image was developed. Eighty images of blastocysts that led to live births and 80 images of blastocysts that led to aneuploid miscarriages were used to create an AI‐based method with 5‐fold cross‐validation retrospectively for classifying embryos. Results The logistic regression method showed the best results. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 0.65, 0.60, 0.70, 0.67, and 0.64, respectively. Area under the curve was 0.65 ± 0.04 (mean ± SE). Estimated probability of belonging to the live birth category was found significantly related to the probability of live birth (P

We developed an artificial intelligence (AI) method for estimating fetal weights of Japanese fetuses based on the gestational weeks and the bi-parietal diameter, abdominal circumference, and femur length. The AI comprised of neural network architecture was trained by deep learning with a dataset that consists of ± 2 standard devia-tion (SD), ± 1.5SD, and ± 0SD categories of the approved standard values of ultrasonic measurements of the fetal weights of Japanese fetuses (Japan Society of Ultrasonics in Medicine [JSUM] data). We investigated the residuals and compared 2 other regression formulae for estimating the fetal weights of Japanese fetuses by t-test and Bland-Altman analyses, respectively. The residuals of the AI for the test dataset that was 12.5% of the JSUM data were 6.4 ± 2.6, −3.8 ± 8.6, and −0.32 ± 6.3 (g) at −2SD, +2SD, and all categories, respectively. The residu-als of another AI method created with all of the JSUM data, of which 20% were randomized validation data, were −1.5 ± 9.4, −2.5 ± 7.3, and −1.1 ± 6.7 (g) for −2SD, +2SD, and all categories, respectively. The residuals of this AI were not different from zero, whereas those of the published formulae differed from zero. Though vali-dation is required, the AI demonstrated potential for generating fetal weights accurately, especially for extreme fetal weights.

Objectives The development of the artificial intelligence (AI) classifier to recognize fetal facial expressions that are considered as being related to the brain development of fetuses as a retrospective, non-interventional pilot study. Methods Images of fetal faces with sonography obtained from outpatient pregnant women with a singleton fetus were enrolled in routine conventional practice from 19 to 38 weeks of gestation from January 1, 2020, to September 30, 2020, with completely de-identified data. The images were classified into seven categories, such as eye blinking, mouthing, face without any expression, scowling, smiling, tongue expulsion, and yawning. The category in which the number of fetuses was less than 10 was eliminated before preparation. Next, we created a deep learning AI classifier with the data. Statistical values such as accuracy for the test dataset and the AI confidence score profiles for each category per image for all data were obtained. Results The number of fetuses/images in the rated categories were 14/147, 23/302, 33/320, 8/55, and 10/72 for eye blinking, mouthing, face without any expression, scowling, and yawning, respectively. The accuracy of the AI fetal facial expression for the entire test data set was 0.985. The accuracy/sensitivity/specificity values were 0.996/0.993/1.000, 0.992/0.986/1.000, 0.985/1.000/0.979, 0.996/0.888/1.000, and 1.000/1.000/1.000 for the eye blinking, mouthing, face without any expression, scowling categories, and yawning, respectively. Conclusions The AI classifier has the potential to objectively classify fetal facial expressions. AI can advance fetal brain development research using ultrasound.

Purpose Recently, endoscopic surgeries are widely performed in the gynecological field. Several studies on the use of local anesthesia for pain control after laparoscopic surgery have been conducted; however, its effects remain controversial. Herein, a randomized control study on gynecological laparoscopic surgeries was conducted to analyze the effectiveness of local anesthesia on postoperative pain. Methods Patients who underwent laparoscopic surgeries due to gynecologic benign diseases or endometrial cancer in the early stage were enrolled, and randomly divided into intervention (injected with levobupivacaine), and control (injected with saline) groups. The primary outcome was the dosage of analgesic consumption within 12 hours postoperatively. Results A total of 147 patients were enrolled in the intervention group and 147 in the control group. The outcome of local anesthesia was not significantly different between the two groups during the whole analysis. We analyzed the effects of local anesthesia in the laparoscopic surgery subgroup. The dosage of analgesic consumption within 12 h after a laparoscopic hysterectomy (TLH) or TLH with pelvic lymph node dissection (TLH+PLD) in the intervention group was significantly smaller than that in the control group. Conclusion Local infiltration anesthesia can effectively reduce postoperative pain in patients who underwent TLH or TLH +PLD.

The aim of the present study was to explore the feasibility of using deep learning, such as artificial intelligence (AI), to classify cervical squamous epithelial lesions (SILs) from colposcopy images combined with human papilloma virus (HPV) types. Among 330 patients who underwent colposcopy and biopsy performed by gynecological oncologists, a total of 253 patients with confirmed HPV typing tests were enrolled in the present study. Of these patients, 210 were diagnosed with high-grade SIL (HSIL) and 43 were diagnosed with low-grade SIL (LSIL). An original AI classifier with a convolutional neural network catenating with an HPV tensor was developed and trained. The accuracy of the AI classifier and gynecological oncologists was 0.941 and 0.843, respectively. The AI classifier performed better compared with the oncologists, although not significantly. The sensitivity, specificity, positive predictive value, negative predictive value, Youden's J index and the area under the receiver-operating characteristic curve ± standard error for AI colposcopy combined with HPV types and pathological results were 0.956 (43/45), 0.833 (5/6), 0.977 (43/44), 0.714 (5/7), 0.789 and 0.963±0.026, respectively. Although further study is required, the clinical use of AI for the classification of HSIL/LSIL by both colposcopy and HPV type may be feasible.

ObjectiveTo assess the success rates of five fetal cardiac views using HDlive Flow (Silhouette) with spatiotemporal image correlation (STIC) in the second and third trimesters of pregnancy, and to verify the feasibility of obtaining five cardiac views by volumes.MethodsOne hundred and eighteen normal fetuses at 18–21 and 28–31 weeks of gestation were studied using HDlive Flow (Silhouette) with STIC to assess the success rates of five fetal cardiac views (frontal, spatial three-vessel, panoramic, posterior, and right lateral views). Target structures in each cardiac view were evaluated. “Good” was assigned when all structures were noted, “Fair” when only one structure was missed, and “Poor” when two and more structures could not been detected.ResultsThere were no significant differences in success rates of each cardiac view between 18–21 and 28–31 weeks of gestation. The rate of “Good” with a spatial three-vessel view was significantly higher than that with other cardiac views at 18–21 and 28–31 weeks, respectively (P ConclusionFive cardiac views using HDlive Flow (Silhouette) with STIC may become an adjunctive and useful tool in fetal cardiac examination.

Aim To investigate the feasibility of a novel method using artificial intelligence (AI), in which the fibrinogen criterion was determined by the quantitative relation between the distributions of fibrin/fibrinogen degradation products (FDPs) and fibrinogen. Methods A dataset of 154 deliveries comprising more than 2000 g of blood lost due to hemorrhage, excluding disseminated intravascular coagulation (DIC), among patients from eight national perinatal centers in Japan from 2011 to 2015 were obtained. The fibrinogen threshold criterion was identified by using the function that best fit the distributions of FDP as determined by AI. FDP production was described by differential equations using a dataset containing fibrinogen levels less than the fibrinogen criterion and solved numerically. Results A fibrinogen level of 237 mg/dL as the threshold criterion was obtained. The FDP threshold criteria were 2.0 and 8.5 mg/dL for no coagulopathy and a failed coagulation system, respectively. Conclusion The fibrinogen threshold criterion for patients with massive hemorrhage excluding DIC at delivery were obtained by selecting the functions that best fit the distributions of FDP data by using AI.

The aim of the present study was to explore the feasibility of using deep learning as artificial intelligence (AI) to classify cervical squamous epithelial lesions (SIL) from colposcopy images. A total of 330 patients who underwent colposcopy and biopsy by gynecologic oncologists were enrolled in the current study. A total of 97 patients received a pathological diagnosis of low-grade SIL (LSIL) and 213 of high-grade SIL (HSIL). An original AI-classifier with 11 layers of the convolutional neural network was developed and trained. The accuracy, sensitivity, specificity and Youden's J index of the AI-classifier and oncologists for diagnosing HSIL were 0.823 and 0.797, 0.800 and 0.831, 0.882 and 0.773, and 0.682 and 0.604, respectively. The area under the receiver-operating characteristic curve was 0.826±0.052 (mean ± standard error), and the 95% confidence interval 0.721-0.928. The optimal cut-off point was 0.692. Cohen's Kappa coefficient for AI and colposcopy was 0.437 (P

Purpose To identify the multivariate logistic regression in a combination (combination method) involving artificial intelligence (AI) classifiers in images of blastocysts along with a conventional embryo evaluation (CEE) to predict the probability of accomplishing a live birth in patients classified by maternal age. Methods Retrospectively, a total of 5691 blastocysts were enrolled. Images captured 115 hours or 139 hours if not yet sufficiently large after insemination were classified according to age as follows

We devised biomathematics-based formulae to estimate the standard values of fetal growth of Japanese after 22 weeks' gestation. The growth rates of bi-parietal diameter (BPD), abdominal circumference (AC), femur length (FL), and estimated fetal body weight (EFBW) at the time of gestation were assumed to be proportional to the product of the value at the time and the rest value of an unknown maximum value, respectively. The EFBW was also assumed to follow a multiple logistic function of BPD, AC and FL to fit the standard values of Japanese fetuses published by the Japan Society of Ultrasonics in Medicine. The Mann-Whitney test was used for statistical analysis. The values as a function of gestational day, t, were as follows: BPD(t)=99.6/(1+exp (2.725−0.01837＊t)) (mm); AC(t)=39.7/(1+exp (2.454−0.01379＊t)) (cm); FL(t)=79.6/(1+exp (2.851−0.01710＊t)) (mm); EFBW(t)=8045.1/(1+exp (6.028−0.06582＊BPD(t)−0.1469＊AC(t)+ 0.07377＊FL(t))) (g). EFBW as a function of BPD, AC and FL was as follows: EFBW=8045.1/(1+exp (4.747+ 0.02584＊BPD+0.1010＊AC−0.1416＊FL)) (g). When the BPD, AC and FL were at −2 standard deviation (SD), −1SD, mean and + 2SD, the EFBW values calculated by the formula were statistically closer to the standard values than conventional formulas with p-values of 4.871×10−7, 4.228×10−7, 9.777×10−7 and 0.028, respectively. The formulae based on biomathematics might be useful to estimate the fetal growth standard values.

Objective. To clarify the pharmacological advantage of carboplatin-based intraperitoneal chemotherapy using the three-compartment mathematical model. Methods. Eleven consecutive patients in one institution underwent intraperitoneal administration of carboplatin, and 11 consecutive patients in another institution received intravenous administration. Carboplatin (AUC = 6 mg × min/ml) was diluted in 500 ml 5% glucose and administered either as an intraperitoneal bolus infusion or intravenous drip infusion during 1 h. Patients undergoing intravenous injection also received an infusion of 500 ml 5% glucose to obtain intraperitoneal samples. Intraperitoneal fluid and blood samples were obtained, immediately and 1, 2, 4, 8, 12, and 24 h after administration. The mathematical model consisting of a three-compartment model was applied to analyze the pharmacokinetics. The model was created with simultaneous differential equations and was solved by the Runge–Kutta method. Results. The rate constants of platinum diffusion from the peritoneal cavity to serum, serum to peritoneal cavity, serum to peripheral space, peripheral space to serum, and elimination were 0.94 ± 0.79 (mean ± SD), 1.28 ± 2.50, 16.50 ± 9.26, 0.99 ± 0.62, and 4.14 ± 1.45 (h −1 ), respectively. When the theoretical pharmacological concentration of platinum was calculated using this mathematical model, 24-h platinum AUC in the serum was exactly the same regardless of intraperitoneal or intravenous administration of carboplatin. However, the 24-h platinum AUC in the peritoneal cavity was approximately 17 times higher when carboplatin was administered by the intraperitoneal route. Conclusion. The present pharmacological analysis suggests that intraperitoneal infusion of carboplatin is feasible not only as an intraperitoneal regional therapy but also as a more reasonable route for systemic chemotherapy.

Here we report imaging studies of a patient with pulmonary benign metastasizing leiomyoma (BML). A 44-year-old woman who underwent a hysterectomy for uterine cellular leiomyoma presented with abnormal shadows on a chest X-ray. Chest computed tomography (CT) revealed multiple well-defined nodules in both lungs. Chest magnetic resonance imaging (MRI) indicated these nodules as T1-low/T2-high intensity lesions. Contrast-enhanced MRI indicated these nodules as well-enhanced lesions, while 18F-fluorodeoxyglucose positron emission tomography-CT revealed no abnormal accumulation in these nodules. Bilateral lung wedge resections were performed for the largest 2 lesions to confirm the diagnosis, and both nodules were histologically diagnosed as BML.

This study was conducted to determine the gestational age-related reference range of the preload index [peak velocity during atrial contraction (A)/peak velocity during ventricular systole (S)] for the inferior vena cava (IVC), the right hepatic vein, the middle hepatic vein and the left hepatic vein. The slope and the intercept of the regression line for each preload index were compared among the 4 veins using analysis of covariance. Doppler measurements were obtained for the 4 veins of 316 normal fetuses at 22-40 weeks of gestation. A and S values were measured from the recorded flow velocity waveform of each vein and the A/S ratio was calculated as the preload index. The regression lines for the preload index of the 4 veins decreased gradually throughout gestation. Analysis of covariance revealed no significant differences in the slopes of the regression lines for the 4 veins. However, the intercepts of the regression lines for all hepatic veins were significantly higher than that of the regression line for the IVC (P

Purpose The purpose of this work was to investigate the relationship between tumor size on T2-weighted images and parametrial involvement by cervical carcinoma with full-thickness stromal invasion and to evaluate whether the size of the tumor on T2-weighted images is a useful index of parametrial involvement. Method T2-weighted images of 33 patients with cervical carcinoma showed full-thickness stromal invasion. Three-dimensional diameters (transverse, anteroposterior, and craniocaudal) of the primary tumor were measured on T2-weighted images. The area and volume of the tumor were also calculated. Results There were statistically significant differences between the patients with parametrial involvement and those without parametrial involvement for each tumor size. The criteria that showed the best accuracy for each tumor size were determined. Conclusion The tumor size on T2-weighted images is considered to be a useful index for evaluating parametrial involvement by cervical carcinoma with full-thickness stromal invasion.

Objectives: To evaluate by transvaginal ultrasonography (TVU) the thickness of the intact myometrium at the presumed tumor-origin site and to establish criteria for a half myometrial invasion. Methods: A total of 19 successive patients with endometrial cancer who were treated between January 1, 1997, and January 31, 1998, participated in this study. TVU mode B with and without the use of an intrauterine silicon catheter was performed. Results: Using a catheter, the origin site was correctly detected in 15 cases (79%). The best criterion for half myometrial invasion was a 6-mm thickness of the intact myometrium at the origin site. The sensitivity/specificity/accuracy of TVU with the use of a catheter in cases with the correct estimated origin site, were 1.00/0.67/0.86 for myometrial invasion < 1/2, and 0.67/1.00/0.86 for myometrial invasion < 1/2. Conclusion: It is of value to use 6-mm as the criterion for the thickness of the intact myometrium at the estimated tumor-origin site in connection with TVU with the use of a catheter for preoperatively assessing half myometrial invasion.

The purpose of this study was to investigate whether CD44v6 expression correlates with progression or metastasis of cervical cancer. The presence of mRNA for CD44v6 was examined, the association with clinicopathological features was assessed in 80 patients with cervical cancer by reverse transcriptase-polymerase chain reaction (RT-PCR) and subsequent Southern blot hybridisation with an oligonucleotide probe specific for v6. The standard form of CD44 was expressed in all specimens and 53 of 80 cervical cancers expressed an isoform containing exon v6 in combination with other variant exons. In addition, longer size transcripts of more than 1350 bp (long form) were identified in 22 of the 53 CD44v6 positive patients. The expression of CD44v6 and CD44v6 long form in squamous cell carcinomas was significantly higher than that in non-squamous cell carcinomas (P0.001). The expression of CD44v6 long form in histological grade 1 and 2 was significantly higher than that in grade 3 (P0.05). 47 patients in stage Ib-IIb cervical cancers were treated by radical hysterectomy and pelvic lymphadenectomy. We did not find any association between the expression of the long form or the short form of CD44v6 and any pathological features, except for histological cell type. These findings suggest that the regulation of CD44v6 seems to be different between different histological cell types and different tumour grades, and the expression of CD44v6 might not be implicated in the progression and metastasis of cervical cancer.

We examined the presence of mRNA for CD44v6 and assessed the association with clinicopathological features in 42 patients with endometrial cancer by RT-PCR and subsequent Southern blot hybridization with oligonucleotide probe specific for v6. The standard form of CD44 was expressed in all specimens and 20 out of 42 endometrial cancers expressed an isoform containing exon v6 in combination with other variant exons. However, there was no correlation between the expression of CD44v6 and any clinicopathological factors. These findings suggested that the expression of CD44v6 is not implicated in the progression and metastasis of endometrial cancer.

The object of this study is to clarify the association of an angiogenic factor, PD-ECGF (platelet-derived endothelial cell growth factor/thymidine phosphorylase), with clinicopathologic factors, in this case tumor angiogenesis, in epithelial ovarian cancers. Tumor specimens were obtained at the time of surgery from the primary lesion in 60 patients with epithelial ovarian cancer. Histologic cell types were assigned to tumors according to the World Health Organization classification: 26 were classified as serous adenocarcinoma, 15 as endometrioid adenocarcinoma, 9 as mucinous adenocarcinoma, 9 as clear cell carcinoma, and 1 as undifferentiated carcinoma. Surgical staging was based on the international Federation of Gynecology and Obstetrics (FIGO) staging system: 16 were stage I, 6 were stage II, 34 were stage III, and 4 were stage IV. Expression of PD-ECGF was evaluated by immunohistochemical staining. Microvessel density was assessed by immunostaining for factor VIII-related antigen in the most neovascularized area. Stroma cells stained more strongly than cancer cells (80% vs. 33%). The immunopositivity of PD-ECGF in stroma cells was higher in cases of advanced cancer. Expression of PD-ECGF in mucinous adenocarcinomas was significantly higher than that in serous adenocarcinomas, while PD-ECGF expression in clear cell carcinomas was significantly lower. The microvessel density in the cases with marked PD-ECGF-positive stroma cells was significantly higher than that in the cases with absent/minimal PD-ECGF-positive stroma cells (P

The aim of this study is to address the role of mdm-2-gene amplification in the tumorigenesis of uterine sarcomas. Differential PCR with DNA from formalin-fixed paraffin-embedded specimens was employed in 12 patients with uterine sarcomas. We detected mdm-2-gene amplification in 4 out of 12 uterine sarcomas. The estimated copy number of the mdm-2 gene ranged from 4 to 13. Positive cases included 1 leiomyosarcoma and 3 carcinosarcomas, however, there was no correlation between mdm-2-gene amplification and clinicopathological characteristics. Over-expression of p53 protein was also immunohistochemically studied in the same series of patients: 4 out of 8 carcinosarcomas displayed p53 immunoreactivity. Taking these results together, only one carcinosarcoma was found to have both mdm-2-gene amplification and p53 over-expression. In contrast, half of the patients were found to have alterations either of mdm-2 or of p53. These findings support the notion that mdm-2-gene amplification might be an alternative mechanism for escaping from the regulatory pathway of p53 to suppress cell growth.

The purpose of this study was to investigate the efficacy of dynamic MR imaging in the assessment of parametrial involvement by cervical carcinoma with full-thickness stromal invasion on thin-section oblique axial T2-weighted images. Dynamic MR images of 24 patients with cervical carcinoma with full-thickness stromal invasion on thin-section oblique axial T2-weighted images were evaluated with pathologic correlation. Dynamic MR imaging was performed using a turboFLASH, 3D-FISP, or 2D-FLASH technique. The imaging planes of dynamic MR imaging were oblique axial planes of the uterine cervix. Dynamic MR imaging was performed twice, once for the early phase (40 to 60 sec after the administration of contrast media) and once for the late phase (5 min). Contrast enhancement of the tumor was divided into six types. Type I, cervical stroma with low signal intensity surrounding a tumor with high signal intensity, was seen in the early phase of dynamic MR imaging; type II-RR, the hyperintense rim was seen from the early phase to the late phase; type II-RO, the hyperintense rim was seen in the early phase only; type II-OR, the hyperintense rim was seen in the late phase only; type II-O, the hyperintense rim was not seen at all; and type III, tumor invasion with high signal intensities was seen beyond the cervical stroma in the early phase of dynamic MR imaging. The numbers for each type of cervical carcinoma on dynamic MR images were as follows: type I, four parametrial sites; type II-RR, 0; type II-RO, 0; type II-OR, 13; type II-O, 14; and type III, one. Three-dimensional diameters (transverse, craniocaudal, and anteroposterior) of the primary tumor were measured using dividers. All parametrial sites of type I and type II-OR showed no parametrial involvement. One parametrial site of type III and three parametrial sites of type II-O showed parametrial involvement, and 11 of type II-O showed no parametrial involvement. None of the patients showed type I-RR or type II-RO. When type I and type II-OR were categorized as criteria of no parametrial involvement and type III and transverse diameters of 3.5 cm or over classified as type II-O were categorized as criteria of parametrial involvement, the rate of diagnostic accuracy was 95.8%. Dynamic MR imaging is considered to be substantially useful in the assessment of parametrial involvement with cervical carcinoma with full-thickness stromal invasion by thin-section oblique axial T2-weighted images.

A rapid quantitative real-time PCR method was employed to quantify the copy number of E2 and E6 genes for analysis of the physical status of human papillomavirus type 16 (HPV-16) DNA. Significant differences with respect to both copy numbers were found when more than 40% of HPV-16 DNA was integrated with disruption of the E2 gene in an experimental model. The physical status of HPV-16 DNA in 50 clinical samples was exclusively episomal in 21 cases (42%), concomitant in 14 cases (28%), and integrated in 15 cases (30%). The prevalence of integrated and/or concomitant forms of HPV-16 DNA increased with progression of cervical disease. Four of 11 cervical intraepithelial neoplasia involved integrated forms of HPV-16 DNA partially or exclusively. This rapid, sensitive technique is useful in the analysis of the physical status of HPV DNA.

9568 Background: Thirty percent of cancer patients are reported to suffer from psychological distress which detracts from treatment adherence, but that is often underestimated in clinical settings....

Purpose: The pharmacodynamic effects of cis-diammine(glycolato)platinum (nedaplatin, 254-S) in vitro have been reported, but the dosage and exposure time in vitro have not always been based on clinical observations of the drug's actions in vivo. Regardless of the actual exposure conditions used, the effect of cell-cycle nonspecific anticancer agents such as nedaplatin is believed to depend on the area under the drug concentration-time curve (AUC). In this study, we evaluated the pharmacodynamics of nedaplatin in vitro, especially in relation to its AUC dependency, in terms of cell survival and DNA crosslinking. Methods: BG-1 human ovarian cancer cells were treated with various concentrations of nedaplatin to simulate the pharmacokinetics of administration in a clinical setting. The BG-1 cells were exposed to nedaplatin dissolved in medium containing serum using constant concentration conditions, either high (maximum 7.69 mg/l) or low (average 1.33 mg/l). These concentrations were based on doses used in clinical studies. We then adjusted the exposure conditions in vitro to simulate the elimination of the drug from serum in vivo as follows: T1/2 α 1.20 h and T1/2 β 2.70 h. The AUC values were set at 4, 8, 16, 25 and 40 mg·h/l for all exposure conditions. A colony-formation assay for the surviving fraction and an alkaline-elution assay for DNA crosslink measurement were done for the pharmacodynamic evaluation with comparison on the basis of the AUC value. Results: Exposure to a low concentration for a long time was the most effective of the exposure conditions at the same AUC value. The greater the AUC value, the higher the crosslink index under all exposure conditions. This index tended to increase particularly after exposure to the low concentration. The natural logarithm of the surviving fraction (Y′) was a linear function of the crosslink index regardless of the drug-exposure condition: ln(Y′)=-87.2x+ln(5.79), R 2=0.89. The threshold cytocidal effect was associated with a crosslink index of 0.02. Conclusion: There was a strong correlation between the cytocidal effect of nedaplatin and DNA crosslink formation. The cytocidal effect and DNA crosslinking in vitro depended on the exposure conditions used to define the AUC. Therefore, a new pharmacokinetic-pharmacodynamic model for nedaplatin must be constructed to investigate the most effective administration procedure in vivo.

Purpose: Cell cycle non-specific anticancer agents such as cis-diamminedichloroplatinum(II) are believed to depend linearly on the value of the area under the drug concentration time curve, which is supported by a mathematical model. However, the quantitative non-linear phenomena of both the cytocidal effect and DNA crosslink formation by cis-diammine(glycolato)platinum (nedaplatin) have been shown in vitro. Therefore, we developed a new mathematical model to explain these phenomena. Methods: We assumed that nedaplatin enters intracellular fluid from medium through simple diffusion to form DNA crosslinks that kill cells. We developed a mathematical model to represent this assumption using differential equations that we then solved using an original computer program. The calculated results were compared with the experimental data. Results: The drug's simple diffusion rate constant, the DNA crosslink formation rate constant, and the crosslink-dependent cell death rate constant in the model were 1.8×10–14 (l h–1), 1.6×108 (l mol–1/2 h–1), 5.45×101 (mol–1), respectively. The model fits the experimental results statistically. The model also demonstrated theoretical proof that continuous exposure at a low dose was superior to the short exposure at a high dose seen in published experimental data. Conclusions: We developed a mathematical model to describe the non-linear pharmacodynamic effect of nedaplatin in vitro. This model may provide a novel drug infusion procedure for cancer patients.

To determine whether alterations of the CDKN2/p16 might be involved in HPV-positive cervical cancers, we examined for alterations of this gene and function of the protein p16 to interact with CDK4 in 5 cervical cancer cell lines. No alteration of this gene was detected. Proteins for p16 and CDK4 were normally expressed and function of p16 to interact with CDK4 was not abrogated in these cell lines. These cell lines were human papillomavirus (HPV)-positive and carried wild-type p53. These findings suggest that phosphorylation of pRb by CDK4 is not critical in the carcinogenesis or in the establishment of HPV-positive cervical cancer cell lines, since HPV E6 or E7 viral-transforming proteins inactivate p53 and pRb tumor suppressor protein function, resulting in deregulated progression of the cell cycle.

The object of this study was to clarify the association of platelet-derived endothelial cell growth factor (PD-ECGF)/thymidine phosphorylase (dThdPase), separately assessed in cancer cells and in stroma cells, with clinicopathological factors including tumor angiogenesis and prognosis in cervical cancer. The expression of PD-ECGF was evaluated by immunohistochemical staining in 92 patients with stage Ib-II cervical cancer. The microvessel count was assessed by immunostaining for factor VIII-related antigen in the most neovascularized area. Microvessel count was significantly higher in tumors with non-squamous cell carcinoma. PD-ECGF expression in cancer cells was significantly higher in tumors with pelvic node metastasis and squamous cell carcinoma. Immunopositivity for PD-ECGF in stroma cells was significantly higher in tumors with large size and deep stromal invasion. The microvessel counts in cases with positive PD-ECGF expression in stroma cells were significantly higher than those in cases with negative PD-ECGF expression in stroma cells (p=0.048). Disease-free survival and overall survival were significantly worse in patients with deep stromal invasion, parametrial involvement, vaginal involvement, lymph-vascular space involvement, pelvic lymph node metastasis and high microvessel count. A multivariate analysis using Cox's proportional hazard model showed that high microvessel count independently predicted disease-free and overall survival. The expression of PD-ECGF in stroma cells may play a crucial role in the promotion of angiogenesis and tumor angiogenesis can be used as a useful prognostic marker for cervical cancer.

The association between the expression of vascular endothelial growth factor (VEGF) and clinicopathological factors has scarcely been examined in cervical cancer. This study examines the level of VEGF messenger RNA (mRNA) expression in invasive cervical cancer and its association with clinicopathological features including microvessel density. The level of VEGF mRNA was assessed by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) using beta-actin as an internal control in 66 patients with stages Ia-IVb invasive cervical cancer. In 42 patients who underwent surgery, the microvessel count was also assessed by immunostaining for factor VIII-related antigen in the most neovascularised area of the specimen. The highest level of VEGF mRNA expression was observed in early invasive cervical cancers. Except for stage IVb, the stage of the disease inversely correlated with the level of VEGF mRNA (P0.05). There was no significant difference in the level of VEGF mRNA with respect to histological cell types. 38 patients with stages Ib-IIb cervical cancer underwent radical hysterectomy and pelvic lymphadenectomy. There was no significant difference in the level of VEGF mRNA with respect to lymph node metastasis, depth of stromal invasion, tumour size, parametrial involvement or vaginal involvement among these patients. A significant relationship was found between the microvessel density and the level of VEGF mRNA (P0.01). These findings provide evidence that the expression of VEGF is involved in the promotion of angiogenesis in cervical cancer and plays an important role in early invasion.

Objective: It is well known that the serum level of Interleukin-6 (IL-6) correlates with the level of C-reactive protein (CRP). The purpose of this study is to determine the significance of CRP as a prognostic factor in epithelial ovarian cancer. Study Design: The present study is comprised of 120 patients with epithelial ovarian cancer from 1985 to 1992. In this study, CRP levels above 50 mg/l were considered high CRP. Univariate and multivariate analyses were performed to identify clinicopathological variables associated with poor survival. Results: The serum CRP value was significantly associated with the volume of ascites (P=0.000004). Univariate analysis showed that the FIGO stage, primary tumour diameter, size of residual tumour, histologic grade, volume of ascites and high serum level of CRP were significant prognostic factors. Cox's multivariate proportional hazard model showed that histologic grade was the most important prognostic factor (P=0.0026). FIGO stage and volume of ascites were also independent factors for 5-year survival (P=0.0310 and P=0.0216, respectively). However, the serum CRP value was not an independent prognostic factor. Conclusion: CRP is an adverse prognostic factor in univariate analysis, but not in multivariate analysis.

The objective of this study is to clarify the association between the expression of two types angiogenic factors, vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF)/thymidine phosphorylase(dThdPase) and clinicopathological features, including tumor angiogenesis, in cervical cancers.The expression of VEGF and PD-ECGF was evaluated by immunohistochemical staining of tumor specimens from 73 patients with stage Ib-IIb cervical cancer (51, squamous cell carcinoma; 19, adenocarcinoma; 3, adenosquamous carcinoma) who underwent radical hysterectomy. The microvessel density was assessed by immunostaining for factor VIII-related antigen in the most neovascularized area.The microvessel density in adenocarcinomas was significantly higher than that in squamous cell carcinomas (P0.01). The intensity of VEGF expression in adenocarcinomas was significantly stronger than that in squamous cell carcinomas (P0.05). In contrast, the expression of PD-ECGF in squamous cell carcinomas was significantly higher than that in adenocarcinomas (P0.0001) and adenosquamous carcinomas (P0.01). There was an inverse relationship between VEGF expression and PD-ECGF expression among all patients studied (P0.001). The microvessel density was significantly correlated with the intensity of VEGF expression (P0.05). In contrast, there was no correlation between the microvessel density and the expression of PD-ECGF.The expression of VEGF appears to be involved in the promotion of angiogenesis in cervical cancers. Furthermore, we propose that angiogenic pathways may be different in different types of cervical cancers.

We present case of a 57-year-old Japanese woman a 9 cm-size primary malignant melanoma of the uterine cervix. MRI demonstrated a low-signal T1-weighted spin echo image and hyperperfusion indicated by Gd-DTPA enhancement. The sequence! analysis of the MTS1/CDK4I gene revealed no deletion or mutation. The results of cytological, pathological, and electron microscopy tests are also presented.

It is very rare to find endometrial cancers arising within a short period following childbirth, presumably because pregnancy has a protective effect against endometrial cancer mediated by elevated secretion of progesterone. We present the case of a 30-year-old Japanese woman with stage IIIC endometrial cancer that was found 7 months after childbirth. The patient was treated with surgery followed by 6 cycles of intravenous combination chemotherapy and oral administration of medroxyprogesterone acetate. Histopathological examination of surgical specimen revealed poorly differentiated adenosquamous carcinoma of the endometrium with deep myometrial invasion, cervical stromal involvement, and pelvic and paraaortic lymph node metastases. The disease progressed rapidly and the patient died of the disease.