Flexible Magnifying Endoscopy with Narrow Band Imaging for Diagnosing Uterine Cervical Neoplasms: A Multicenter Prospective Study.

We aimed to investigate the diagnostic ability of magnifying endoscopy with narrow band imaging (ME-NBI) for cervical intraepithelial neoplasia grade 2 or worse (CIN2+). This was a multicenter prospective study. Eligible patients had positive Pap smear results or follow-up high-grade cytology or CIN3 diagnosed in referring hospitals. Patients underwent ME-NBI by a gastrointestinal endoscopist, followed by colposcopy by a gynecologist. One lesion with the worst finding was considered the main lesion. Punch biopsies were collected from all indicated areas and one normal area. The reference standard was the highest histological grade among all biopsy specimens. The primary endpoint was the detection rate of patients with CIN2+ in the main lesion. The secondary endpoints were diagnostic ability for CIN2+ lesions and patients' acceptability. We enrolled 88 patients. The detection rate of ME-NBI for patients with CIN2+ was 79% (95% CI: 66-88%; p = 1.000), which was comparable to that of colposcopy (79%; p = 1.000). For diagnosing CIN2+ lesions, ME-NBI showed a better sensitivity than colposcopy (87% vs. 74%, respectively; p = 0.302) but a lower specificity (50% vs. 68%, respectively; p = 0.210). Patients graded ME-NBI as having significantly less discomfort and involving less embarrassment than colposcopy. ME-NBI did not show a higher detection ability than colposcopy for patients with CIN2+, whereas it did show a better patient acceptability.

Quality Assessment of Endoscopic Forceps Biopsy Samples under Magnifying Narrow Band Imaging for Histological Diagnosis of Cervical Intraepithelial Neoplasia: A Feasibility Study.

The current standard for diagnosing cervical intraepithelial neoplasia (CIN) is colposcopy followed by punch biopsy. We have developed flexible magnifying endoscopy with narrow band imaging (ME-NBI) for the diagnosis of CIN. Here, we investigated the feasibility of targeted endoscopic forceps biopsy (E-Bx) under guidance of ME-NBI for the diagnosis of CIN. We prospectively enrolled 32 consecutive patients with confirmed or suspected high-grade CIN undergoing cervical conization. Next to colposcopy, the same patients underwent ME-NBI just before conization. ME-NBI was performed, and 30 E-Bx samples were taken from lesions suspicious for high-grade CIN and 15 from non-suspicious mucosa. We recalled 82 punch biopsy (P-Bx) specimens taken from lesions suspicious for high-grade CIN under colposcopic examination before enrollment. The proportion of sufficient biopsy samples, which had an entire mucosal layer with subepithelial tissue, for the diagnosis of CIN was evaluated by both methods. Performance of targeted E-Bx for the final diagnosis of at least high-grade CIN was calculated. Seventeen P-Bx specimens were unavailable. The proportion of sufficient samples with E-Bx was 84%, which was similar to that with P-Bx (87%) (p = 0.672). The sensitivity, specificity, and accuracy of ME-NBI using E-Bx was 92%, 81%, and 88%, respectively. In conclusion, ME-NBI-guided E-Bx samples were feasible for histological diagnoses of CIN, and further investigation of its diagnostic accuracy is warranted.

Prediction of postnatal developmental disabilities using the antenatal fetal neurodevelopmental test: KANET assessment.

Objective To assess the usefulness of the antenatal fetal neurodevelopmental test for the prediction of postnatal developmental disabilities. Methods Fetal behavior was assessed with Kurjak's antenatal neurodevelopmental test (KANET) using four-dimensional ultrasound between 28 and 38 weeks of gestation. A score range of 0-5 was characterized as abnormal, from 6 to 9 was considered borderline, and 10-16 was normal. After birth, follow-up was conducted for at least 2 years in all fetuses. Results There were 337 normal (95.47%) and 16 borderline (4.53%) cases among the 353 cases studied, whereas there was no abnormal case. Five cases with postnatal developmental disabilities (one case of Werdig-Hoffmann disease diagnosed just after delivery, one case of autism spectrum disorder diagnosed at 24 months, one case of Ullrich congenital muscular dystrophy diagnosed at 9 months and two cases of developmental disorders diagnosed at age 3 and 18 months) were noted among the 337 normal cases (1.48%), whereas three cases with developmental disabilities (one case of motor development delay diagnosed at 6 months, one case of Duchenne muscular dystrophy diagnosed at 18 months and one case of autism spectrum disorder diagnosed at age 30 months) were found among the 16 borderline cases (18.75%). There was a significant difference in the prevalence of postnatal developmental disabilities between the normal and borderline KANET groups (P<0.001). Conclusion Our results suggest that the KANET assessment may be a useful diagnostic modality for the prediction of postnatal developmental disabilities.

Flexible magnifying endoscopy with narrow band imaging for the diagnosis of uterine cervical tumors: A cooperative study among gastrointestinal endoscopists and gynecologists to explore a novel microvascular classification system.

Narrow band imaging with magnifying endoscopy (NBI-ME), which is useful for the assessment of micro-vessels, has excellent diagnostic potential for early gastrointestinal epithelial neoplasia. Conventional diagnostic tools for uterine cervical epithelial tumors are still unsatisfactory. An accurate diagnostic tool for uterine cervical epithelial tumors is required to preserve the reproductive ability of young women with uterine cervical tumors. Flexible NBI-ME was performed in patients with cervical squamous cell lesions that required further examinations based on their Pap smear results (cytology ≥ low-grade squamous intraepithelial lesion) at Kagawa University Hospital between April 2014 and April 2015. NBI-ME results concordant with the punch biopsy sites were compared with the histological results. A retrospective review of the NBI-ME images identified abnormal NBI-ME results regarding micro-vascular patterns. All images were categorized as having abnormal features. NBI-ME revealed the following vascular pattern differences of different stage tumors: Dot-like vessels without irregular arrangements and high density in cervical intraepithelial neoplasia (CIN) CIN1-CIN2; dot-like vessels with irregular arrangements and high density in CIN3-carcinoma in situ; crawling vessels in minimum invasive cancer; and willow branch vessels and new tumor vessels in invasive cancer. NBI-ME may be an effective diagnostic tool for uterine cervical epithelial tumors, which may lead to the establishment of a novel classification system.

Is there a sex difference in fetal behavior? A comparison of the KANET test between male and female fetuses.

AIM: To evaluate the sex difference in fetal behavior between male and female fetuses. METHODS: Fetal behavior was assesed by Kurjak's antenatal neurodevelopmental test (KANET) using four-dimensional (4D) ultrasound between 28 and 39 weeks of gestation. Fifty-nine male and 53 female fetuses in middle- and high-class nulliparaous Japanese women were studied. The total value of the KANET score and values of each parameter (eight parameters) were compared. RESULTS: The total KANET score was normal in both groups, and there was no significant difference in the total KANET score. When individual KANET parameters were compared, no significant differences were noted in all eight parameters. CONCLUSION: Our results show that there is no difference in fetal behavior between male and female fetuses in the third trimester of pregnancy. These results suggest that 4D ultrasound study examining fetal behavior does not need to consider the factor of fetal sex.

Is yolk sac tumor related to the pathophysiology of low birthweight?

An 8-year-old Japanese girl was admitted with an ovarian yolk sac tumor. Regarding birth history, the patient had been delivered by cesarean section at 25 weeks of gestation with a birthweight of 711g. She had required neonatal intensive care including oxygenation, various medications, and tests. After surgery and chemotherapy, there was no recurrence for 2 years, at the time of writing. Yolk sac tumor, which is a malignant germ cell tumor, is rare in children. Although the cause and risk factors are unclear, it has been reported that malignant germ cell tumors in childhood have been associated with pathophysiology at birth. Given that premature infants are more likely to survive due to advances in perinatal care, it is expected that such cases will increase in the near future. We suggest that children born prematurely require careful follow up.

Does ethnicity have an effect on fetal behavior? A comparison of Asian and Caucasian populations.

AIM: This study aimed to evaluate the ethnic difference in fetal behavior between Asian and Caucasian populations. METHODS: Fetal behavior was assesed by Kurjak's antenatal neurodevelopmental test (KANET) using four-dimensional (4D) ultrasound between 28 and 38 weeks of gestation. Eighty-nine Japanese (representative of Asians) and seventy-eight Croatian (representative of Caucasians) pregnant women were studied. The total value of KANET score and values of each parameter (eight parameters) were compared. RESULTS: The total KANET score was normal in both populations, but there was a significant difference in total KANET scores between Japanese (median, 14; range, 10-16) and Croatian fetuses (median, 12; range, 10-15) (P<0.0001). When individual KANET parameters were compared, we found significant differences in four fetal movements (isolated head anteflexion, isolated eye blinking, facial alteration or mouth opening, and isolated leg movement). No significant differences were noted in the four other parameters (cranial suture and head circumference, isolated hand movement or hand to face movements, fingers movements, and gestalt of general movements). CONCLUSION: Our results suggest that ethnicity should be considered when evaluating fetal behavior, especially during assessment of fetal facial expressions. Although there was a difference in the total KANET score between Japanese and Croatian populations, all the scores in both groups were within normal range. Our results indicate that ethnical differences in fetal behaviour do not affect the total KANET score, but close follow-up should be continued in some borderline cases.

Four-dimensional color Doppler reconstruction of the fetal heart with glass-body rendering mode.

The investigators present their experience with normal fetal cardiac structures and congenital heart anomalies reconstructed using 4-dimensional color Doppler with glass-body rendering mode and spatiotemporal image correlation. Two normal fetuses and 6 fetuses with congenital heart anomalies (1 case each of ventricular septal defect, Ebstein's anomaly, hypoplastic left heart syndrome, and ductus arteriosus aneurysm and 2 of double-outlet right ventricle) at 26 to 36 weeks' gestation were studied using 4-dimensional color Doppler with glass-body rendering mode. In normal fetal hearts, blood flow through the 4 cardiac chambers and crisscross arrangements of the pulmonary artery and aorta were clearly recognized. In the fetus with a ventricular septal defect, significant shunt flow through the defect between the left and right ventricles was evident. In the fetus with Ebstein's anomaly, giant tricuspid regurgitant flow was noted. In the fetus with hypoplastic left heart syndrome, large tricuspid regurgitant flow was identified. In the fetuses with double-outlet right ventricles, large aortas and small pulmonary arteries leaving the right ventricles in parallel were clearly shown. In the fetus with a ductus arteriosus aneurysm, an enlarged ductus arteriosus following the pulmonary artery was clearly depicted. In conclusion, fetal 4-dimensional color Doppler may assist in the evaluation of spatial relations between the great vessels and both ventricles and differences in the sizes of the great vessels and cardiac chambers.

4D ultrasound study of fetal facial expressions at 20-24 weeks of gestation.

OBJECTIVE: To assess the frequency of fetal facial expressions at 20-24 weeks of gestation using four-dimensional (4D) ultrasonography and to determine whether there was any correlation between facial expression and gestational age (20-34 weeks). METHODS: The facial expressions of 23 healthy fetuses were examined using 4D ultrasound at 20-24 weeks. Each fetus was recorded continuously for 15 minutes. The frequencies of mouthing, yawning, smiling, tongue expulsion, scowling, sucking, and blinking were assessed and the data combined with those expressions observed at 25-34 weeks of gestation in two previous studies (n = 34) to determine the correlation between gestational age and each of the facial expressions. RESULTS: Mouthing was significantly more frequent than the other six facial expressions at 20-24 weeks (P < 0.05). Yawning was significantly more frequent than smiling, scowling, and blinking (P < 0.05), and sucking was significantly more frequent than smiling, scowling, and blinking (P < 0.05). The frequency of yawning, smiling, tongue expulsion, scowling, and blinking increased with gestational age (P < 0.05). Mouthing movement and sucking frequencies remained constant between 20 and 34 weeks. CONCLUSION: Frequencies of complicated facial expressions such as smiling and scowling may increase with advancing gestation owing to the development of the fetal brain and central nervous system.

HDlive rendering image of adnexal tumors: preliminary report.

BACKGROUND: Our objective is to present our first experience of adnexal tumors reconstructed employing the HDlive rendering mode. METHODS: Seven adnexal tumors (one case each of chocolate cyst, benign cystic teratoma, serous cystadenofibroma, and torsion of the hydrosalpinx, and three cases of ovarian cancer) were studied using the HDlive rendering mode. RESULTS: In the case of the chocolate cyst, the smooth inner wall with numerous tiny projections was clearly identified. In the case of benign cystic teratoma, a smooth hair ball inside the cyst was evident. In the case of the serous cystadenofibroma, a smooth, solid projection and relatively smooth septum were noted. In the three cases of ovarian cancer, numerous irregular papillae and irregular, thick septae were depicted. In the case of the bilateral hydrosalpinx with torsion of the right tube, different fluid contents were recognized. CONCLUSION: The HDlive rendering mode provides anatomically realistic features such as macroscopic specimens for physicians and pathologists due to the complete depiction of the inner surface of the adnexal tumors.

HDlive imaging of the face of fetuses with autosomal trisomies.

BACKGROUND: Our objective is to present our experience of facial dysmorphism reconstructed employing conventional three-dimensional (3D) ultrasound and HDlive in fetuses with autosomal trisomies. METHODS: Seven fetuses with autosomal trisomies (one case of trisomy 13, three of trisomy 18, and three of trisomy 21) at 16-38 weeks' gestation were studied using 3D ultrasound and HDlive. RESULTS: In one case of trisomy 21 at 29 weeks and 5 days, upward slanting eyes, a flattened nose, low-set ears, and the corners of the mouth turned down were noted employing HDlive. In the other two cases of trisomy 21, both techniques showed the same facial findings. In one case of trisomy 18 at 27 weeks and 6 days, a small head accompanied by a prominent back portion of the head, low-set ears, a small jaw, upturned nose, narrow eyelid folds, and widely spaced eyes were identified using HDlive. In the other two cases of trisomy 18, HDlive showed more detailed features of the fetal face compared to conventional 3D ultrasound. In the single case of trisomy 13 at 31 weeks and 1 day, cleft lip and close-set eyes were recognized with both 3D ultrasound and HDlive. CONCLUSION: HDlive can provide clearer facial images than conventional 3D ultrasound. In particular, HDlive is superior to conventional 3D ultrasound for the depiction of eye fissures because of its shadowing effect. HDlive may be a useful diagnostic modality for the antenatal evaluation of subtle fetal facial dysmorphism.

4D ultrasound evaluation of fetal facial expressions during the latter stages of the second trimester.

OBJECTIVE: To assess the frequency of fetal facial expressions at 25-27 weeks of gestation using 4D ultrasound. METHODS: Twenty-four normal fetuses were examined using 4D ultrasound. The face of each fetus was recorded continuously for 15 minutes. The frequencies of tongue expulsion, yawning, sucking, mouthing, blinking, scowling, and smiling were assessed and compared with those observed at 28-34 weeks of gestation in a previous study. RESULTS: Mouthing was the most common facial expression at 25-27 weeks of gestation; the frequency of mouthing was significantly higher than that of the other 6 facial expressions (P<0.05). Yawning was significantly more frequent than the other facial expressions, apart from mouthing (P<0.05). The frequencies of yawning, smiling, tongue expulsion, sucking, and blinking differed significantly between 25-27 and 28-34 weeks (P<0.05). CONCLUSION: The results indicate that facial expressions can be used as an indicator of normal fetal neurologic development from the second to the third trimester. 4D ultrasound may be a valuable tool for assessing fetal neurobehavioral development during gestation.

Three- and four-dimensional HDlive rendering image of fetal acrania/exencephaly in early pregnancy.

We present two cases of fetal acrania/exencephaly reconstructed employing the three- (3D) and four-dimensional (4D) HDlive rendering mode in early gestation. Two fetuses with acrania/exencephaly were studied with the 3D/4D HDlive rendering mode at 13 and 15 weeks, respectively. In Case 1, at 13 weeks' gestation, deformed and degenerated brain tissues were clearly shown using the 3D/4D HDlive rendering mode. In Case 2, at 15 weeks and 6 days of gestation, two amniotic bands and acrania/exencephaly were depicted with the 3D/4D HDlive rendering mode. Fragile brain hemispheres with amniotic bands were rocking with fetal movements. The 3D/4D HDlive rendering mode provides physicians, couples, and their families with important and additional information, and has the potential to supplement two-dimensional and conventional 3D ultrasound in diagnosing fetal acrania/exencephaly.

Antenatal three-dimensional sonographic diagnosis of persistent cloaca.

We present a case of fetal persistent cloaca diagnosed by two- (2D) and three-dimensional (3D) sonography and the HDlive rendering mode. 2D sonography revealed a bicornate uterus with hydrometra, bilateral hydrosalpinx, a single umbilical artery, and ascites. 3D sonography and the HDlive rendering mode clearly showed these intra-abdominal structures. To the best of our knowledge, this is the first report of persistent cloaca employing antenatal 3D sonography and the HDlive rendering mode.