Fetal Hepatic Hemangioma Diagnosed in Utero Using Doppler Microvascular Imaging.

A 35-year-old pregnant woman was referred to our institution at 33 weeks' gestation for evaluation of a fetal abdominal tumor. B-mode ultrasonography demonstrated a massive lesion. Bidirectional power Doppler mode showed abundant blood flow surrounding the tumor. On superb micro-vascular imaging, various Doppler signal patterns were observed within the tumor, including diffuse fine dotted-like signals, linear flow, and internal shunt flow. Sequential observations of the tumor and cardiac cycles also revealed pulsatile flow beneath the edges of the tumor and continuous fine flow in the central area, resembling a 'centripetal fill-in' appearance on contrast computed tomography. Therefore, we assumed the fetal tumor to be a hepatic hemangioma. Fetal heart failure was detected at 37 weeks' gestation, and a 2,484-g female infant was delivered with 1- and 5-min Apgar scores of 7 and 8, respectively. A postnatal contrast computed tomography examination showed a progressive centripetal fill-in appearance, leading to a diagnosis of hepatic hemangioma. Kasabach-Merritt syndrome was also noted. Intensive treatment was performed, and the infant was discharged at 3 months after birth. In summary, we experienced a case of hepatic hemangioma diagnosed in utero using superb micro-vascular imaging. And basing seamless postnatal treatments on prenatal imaging findings may help to reduce the perinatal mortality.

Risk Factors in Fetal Ovarian Cysts for Postnatal Adverse Outcomes.

AIM: To investigate the natural history of fetal ovarian cysts and elucidate the risk factors for postnatal adverse outcomes in fetal ovarian cysts. METHODS: The study subjects were 18 cases with ovarian cysts prenatally diagnosed using ultrasonography at our hospital between 2007 and 2020. The subjects were classified by cyst characteristics according to echogenic patterns [simple cyst (S) and complex cyst (C)], changes in echogenic patterns (S-to-S, S-to-C, and C-to-C), and diameters (<40 and ≥ 40 mm). Clinical parameters and outcomes were compared between S and C patterns, S-to-S and S-to-C patterns, and <40 and ≥ 40 mm diameters. RESULTS: Cases with S and C patterns (15 and 3, respectively) had median gestational ages of 35 and 36 weeks, respectively, and maximum cyst diameters of 36 and 57mm, respectively. The number of cases with S-to-S, S-to-C and C-to-C patterns were 11, 4 and 3, respectively. The maximum cyst diameter in cases with S-to-C patterns (58 mm) was larger than that in cases with S-to-S patterns (34 mm) (P<0.05). Placental weight in cases with cysts >40 mm and/or cyst expansion was greater than that in cases with neither or both conditions (P<0.05). Spontaneous resolution (before and after birth) occurred in 8 of 9 and 3 of 9 cases with maximum cyst diameters <40 and ≥ 40 mm, respectively. Ovarian function was lost in 2 cases with S-to-C patterns and in 2 cases with C-to-C patterns. CONCLUSION: Cases with cyst diameters ≥ 40 mm and/or cyst expansion during the late third trimester had greater placental weight and more postnatal adverse outcomes.

Unraveling the enigma: A case of dynamic morphological changes in the niche at 25 weeks of gestation recapitulating the ontogenesis of uterine scar dehiscence.

We present the first report of a case with a peculiar configurational change in the lower uterine segment detected during transvaginal ultrasonography observation over a short period of time at 25 weeks of gestation, predicting the presence of uterine scar dehiscence at term.

Diagnosis of Fetal Abnormalities during the First Trimester.

The quality of prenatal diagnosis of fetal abnormalities has advanced with improved resolution of ultrasound imaging and cytogenetic/molecular analysis. In this article, we briefly review the history of diagnosing fetal abnormalities and the current status of prenatal diagnosis during the first trimester (up to the first 14 weeks' gestation), focusing especially on fetal malformations and chromosomal abnormalities. As for detectable morphological abnormalities, roughly half of all major structural anomalies including those in the central nervous system, cardiovascular system and gastrointestinal system can be detected, if not definitely diagnosed. For screening of chromosomal abnormalities, especially for trisomy 21, ultrasound soft markers such as increased nuchal translucency, maternal serum markers and their combinations have been implemented. More recently, non-invasive prenatal testing, by analyzing cell-free DNA in maternal serum, is now available to detect chromosomal abnormalities with higher predictability. Although invasive chorionic villus sampling offers definite diagnosis for chromosomal abnormalities during the first trimester, non-invasive diagnostic techniques are patient-friendly and promising in the future perspectives on prenatal diagnosis for chromosomal abnormalities.

Difficulty in prenatal diagnosis of the volvulus of the small intestine: A peculiar clinical course of two cases with massive bowel dilatation and loss of peristalsis.

We report two cases of fetal intestinal volvulus (jejunum in case A, ileum in case B) with massive bowel dilatation and loss of peristalsis, which suddenly appeared in the third trimester. The bowel was dilated to different sizes and there were various echogenic patterns of the intestines in case A and a sausage-like appearance in case B. Case A developed polyhydramnios, whereas case B did not. Among 47 cases of fetal intestinal volvulus (29 articles) in which 32 were diagnosed prenatally, almost all cases with a prenatal diagnosis showed "whirlpool sign" or "coffee bean sign" by sonography and/or findings indicating intestinal hemorrhage. Even without these findings, the presence of dilatation of the intestines and loss of peristalsis occurring in the third trimester were diagnostic clues. The presence of different sizes and various patterns of bowel dilation and hydramnios may be helpful for predicting the involved site of intestinal volvulus.

Missing decidual Doppler signals as a new diagnostic criterion for placenta accreta spectrum: A case described using superb microvascular imaging.

We present a case of a 34-year-old pregnant woman with a prior cesarean delivery presenting with placenta previa. Placenta previa accreta was diagnosed from missing decidual flow signals using superb microvascular imaging (SMI). At 31 weeks' gestation, B-mode ultrasonography showed that the placenta was attached to the anterior uterine segment, extending over the internal cervical os. In normally appearing myometrium, SMI demonstrated double layers of flow signals underneath the placental basal plate, corresponding to myometrial and decidual flows. The thin myometrium located on the bladder where sonolucent zones were not visible revealed three different flow patterns in the Doppler signals underneath the basal plate as follows: double layers (both myometrium and decidual tissues present); a single layer (myometrium alone) or no layers (decidual tissues missing). A cesarean hysterectomy was performed at 37 weeks, and histology confirmed the presence of placenta accreta.

Clues and pitfalls in prenatal diagnosis of classic cloacal exstrophy using ultrasonography and magnetic resonance imaging: A case with sequential observation from 17 to 30 weeks' gestation and literature review.

We observed a case of classic cloacal exstrophy (CE) from 17 to 30 weeks' gestation. At 17 weeks, an omphalocele and single umbilical artery (SUA) were diagnosed with a normal female karyotype on amniocentesis. A pelvic cystic adjacent to SUA, considered to be the bladder at 17 weeks, became swollen to form double cysts at 25 weeks. A phallus-like structure along the lower abdomen was additionally detected, leading to the diagnosis of CE. Fetal magnetic resonance imaging (MRI) at 30 weeks confirmed that the phallus-like structure was of intestinal origin. The presence of a non-visualizable bladder together with abdominal wall defect or omphalocele and an elephant trunk-like deformity are key findings in the prenatal diagnosis of classic CE. Fetal MRI was useful in confirming ultrasonographic findings and obtaining additional findings for the diagnosis of CE. We have discussed clues and potential pitfalls in diagnosing CE, with a review of the literature.

Real prevalence of neural tube defects in Japan: How many of such pregnancies have been terminated?

The vital role of folic acid is to reduce the risk of having a neonate afflicted with neural tube defects. The prevalence of neural tube defects (myelomeningocele and anencephaly) has been reported in an incomplete form over the last 40 years in Japan. We aimed to evaluate the total number of neural tube defects including those delivered or terminated, to clarify the proportion of those terminated, and to internationally compare their prevalence. Through information on >311 000 deliveries obtained from 262 hospitals/clinics for 2 years of 2014 and 2015, we identified that the rate of total neural tube defects (termination of pregnancy, live births and stillbirths) was 8.29 per 10 000 deliveries for the year 2014 and was 8.72 for 2015, which were 1.5 and 1.6 times higher than the respective values (live births and stillbirths) reported. It is also observed that the ratio of the total number of myelomeningocele (termination of pregnancy, live births, and stillbirths) to that of anencephaly was approximately 1:1.2, that a half of pregnancies afflicted with neural tube defects were terminated, and that the proportion of termination of pregnancy due to myelomeningocele and due to anencephaly was 20% and 80%, respectively. Internationally, the real prevalence of neural tube defects in Japan was comparatively high, ranking fifth among the seven developed countries. In conclusion, the real prevalence of total neural tube defects was approximately 1.5 times higher than that currently reported by the Japan Association of Obstetricians and Gynecologists.

Enhancement of humoral and cell mediated immune response to HPV16 L1-derived peptides subsequent to vaccination with prophylactic bivalent HPV L1 virus-like particle vaccine in healthy females.

Currently prophylactic HPV16/18 L1 virus-like particle (VLP) vaccines are employed with great success for the prevention of HPV infection. However, limited information is available regarding the immune responses against human papillomavirus (HPV) 16/18 L1 subsequent to HPV16/18 L1 VLP vaccination, primarily due to the lack of widely used assays for immune monitoring. The aim of the present study was to identify HPV16 L1-derived B and T cell epitopes for monitoring the immune responses after HPV16/18 L1 VLP vaccination in healthy females. The levels of immunoglobulin G (IgG), IgE, IgA and IgM reactive to HPV16 L1-derived peptides were measured by multiplex bead suspension assay. Following detailed B cell epitope mapping, T cell responses specific to HPV16 L1-derived peptides were evaluated by an IFN-γ ELISPOT assay. The levels of IgG, IgM and IgA reactive to 20-mer peptides (PTPSGSMVTSDAQIFNKPYW) at positions 293-312 and 300-319 of HPV16 L1 were significantly increased in the plasma after 2, 7, and 12 months after first vaccination. Detailed epitope mapping identified the amino acid sequence (TSDAQIFNKP) at position 301-310 of HPV16 L1 as an immunogenic B cell epitope. In addition, T cell responses to an HLA-A2- and HLA-A24-restricted epitope (QIFNKPYWL) at position 305-313 of HPV16 L1 were increased following immunization, suggesting that the HPV16/18 L1-VLP vaccination as able to induce specific immune responses in T and B cells simultaneously. The identified B and T cell epitopes may be useful as a biomarker for monitoring the immune responses subsequent to HPV16/18 L1 VLP vaccination. Thus, the present study may provide novel information to improve the understanding of the immune responses to HPV16 L1.

Two cases of acute limbic encephalitis in which symptoms improved as a result of laparoscopic salpingo-oophorectomy.

Anti-N-methyl-D-aspartate (NMDA) receptor antibody encephalitis is an autoimmune form of limbic encephalitis. Eighty percent of patients with anti-NMDA receptor (NMDAR) encephalitis are women, and 39% of those women are reported to have an ovarian teratoma also. When a tumor is also present, prompt surgery can prevent the development of more severe symptoms or the prolongation of symptoms of encephalitis. The current authors encountered two cases in which anti-NMDAR encephalitis was suspected. In these cases, abdominal computed tomography (CT) revealed an ovarian teratoma and both patients underwent a laparoscopic salpingo-oophorectomy. Both patients underwent surgery before a definitive diagnosis was made. Findings in one case did not lead to a diagnosis of anti-NMDAR encephalitis, but symptoms rapidly improved after surgery in both cases. Laparoscopic surgery is minimally invasive, so this approach may be the first step in a treatment algorithm for treatment of a tumor in a patient with anti-NMDAR encephalitis.

Feasibility study of personalized peptide vaccination for recurrent ovarian cancer patients.

CONTEXT: To develop a personalized peptide vaccine (PPV) for recurrent ovarian cancer patients and evaluate its efficacy from the point of view of overall survival (OS), Phase II study of PPV was performed. PATIENTS AND METHODS: Forty-two patients, 17 with platinum-sensitive and 25 with platinum-resistant recurrent ovarian cancer, were enrolled in this study and received a maximum of four peptides based on HLA-A types and IgG responses to the peptides in pre-vaccination plasma. RESULTS: Expression of 13 of the 15 parental tumor-associated antigens encoding the vaccine peptides, with the two prostate-related antigens being the exceptions, was confirmed in the ovarian cancer tissues. No vaccine-related systemic severe adverse events were observed in any patients. Boosting of cytotoxic T lymphocytes or IgG responses specific for the peptides used for vaccination was observed in 18 or 13 of 42 cases at 6th vaccination, and 19 or 29 of 30 cases at 12th vaccination, respectively. The median survival time (MST) values of the platinum-sensitive- and platinum-resistant recurrent cases were 39.3 and 16.2 months, respectively. The MST of PPV monotherapy or PPV in combination with any chemotherapy during the 1st to 12th vaccination of platinum-sensitive cases was 39.3 or 32.2 months, and that of platinum-resistant cases was 16.8 or 16.1 months, respectively. Importantly, lymphocyte frequency and epitope spreading were significantly prognostic of OS. DISCUSSION AND CONCLUSION: Because of the safety and possible prolongation of OS, a clinical trial of PPV without chemotherapy during the 1st to 12th vaccination in recurrent ovarian cancer patients is merited.

[Safety and efficacy of pegylated liposomal Doxorubicin and Carboplatin on platinum-sensitive recurrent epithelial ovarian cancer].

OBJECTIVE: We evaluated the safety and efficacy of pegylated liposomal doxorubicin(PLD)and carboplatin(CBDCA)(CD) for platinum-sensitive recurrent epithelial ovarian cancer. METHODS: From December 2010 to June 2011, 9 eligible patients with histologically confirmed, recurrent epithelial ovarian cancer, which was deemed platinum-sensitive, were enrolled onto the study. PLD(30mg/m2)and CBDCA(area under the curve[AUC]5)were administered intravenously on day 1 of the cycle. The chemotherapy regimen was repeated every 4 weeks, until disease progression or completion of 6 cycles. RESULTS: A total of 49 treatment cycles of CD were administered to 9 patients. The median platinum-free interval was 18.3 months. Patients with Grade 3/4 hematological toxicities were observed to have leucopenia(11.1%), neutropenia(44.4%), anemia (22.2%), and thrombocytopenia (22.2%). No Grade 3/4 non-hematological toxicities were observed, and no treatment related death occurred. Seven patients(77.7%)responded to CD(4 complete responses and 3 partial responses). The median progression-free survival and overall survival times were 15.1 and 23.7 months. CONCLUSION: CD treatment seems to be a safe and effective chemotherapy regimen for platinum-sensitive recurrent epithelial ovarian cancer.

A case of minimal uterine serous carcinoma with distant lymph node metastasis without peritoneal dissemination.

A 61-year old woman underwent total abdominal hysterectomy and pelvic lymph node dissection under the diagnosis of endometrial cancer. Although pelvic lymph nodes were positive for adenocarcinoma with psamomma bodies, no other lesion that was a primary lesion was verified. A postoperative study revealed the existence of para-aortic lymph node and supraclavicular lymph node metastases. Therefore, the endometrial biopsy specimen was reviewed. With the findings of p53 positivity by immunohistochemistry in the papillary part, the final histopathological diagnosis was changed to endometrial serous adenocarcinoma. Postoperative chemotherapy followed by radiotherapy for supraclavicular lymph node metastasis achieved complete response. This type of tumor must be considered in a differential diagnosis when metastatic papillary serous carcinoma is detected, but the primary site remains unknown.