Toru Fujioka

Allelotype analysis of gallbladder carcinoma associated with anomalous junction of pancreaticobiliary duct

Anomalous junction of pancreaticobiliary duct (AJPBD) patients has an increased risk of gallbladder and bile duct carcinomas. However, the relevance of carcinoma with AJPBD is not fully clarified. We performed analysis of loss of heterozygosity (LOH) at p53 locus and immunohistochemistry of p53 and K-ras gene mutation in five cases of gallbladder carcinoma associated with AJPBD. LOH of p53 locus and overexpression of p53 were detected in two out of five (40%) and five out of five (100%), respectively, in the present study. K-ras gene mutation at codon 12 and 13 was not detected (0%, 0/5). These results suggest that aberrations of p53 are involved in carcinogenesis of gallbladder carcinoma associated with AJPBD. Next, in order to find the genetic events besides K-ras mutation and overexpression of mutant p53 in this disease, LOH analysis was performed using 72 microsatellite markers. High frequency of allelic loss (> 50%) was found on 2p (81.8%), 4p (50%), 4q (50%), 8q (60%), 9q (50%), 10p (50%), 14p (60%), 14q (50%), 16p (60%), 19p (50%), 21p (50%) and Xp (66.6%). The highest deletion regions on chromosome 2p24 (3/3, 100%), 14q22 (3/4, 75%) and 21q22 (3/4, 75%) were found. The present study suggests that gallbladder carcinoma associated with AJPBD has high frequent allelic loss and has two new regions which may harbor putative tumor suppressor genes.

Severe Allergy in a Pregnant Woman after Vaginal Examination with a Latex Glove

Recently case reports about latex allergy were increased. We have experienced severe latex allergy in a pregnant women after vaginal examination with a latex glove. A 33-year-old woman, 38 weeks pregenant, was hospitalized for management of fetal IUGR. She underwent a vaginal examination with a latex glove and soon developed severe anaphylactic reactions. Although two hours later her condition had remarkably improved, regular uterine contractions appeared, and fetal cardiotocogram showed late decelerations. So emergency cesarean section was performed under the situation without using any latex products. She delivered a male infant weighing 2,227 g (–2.21 SD) at 38 weeks gestation. His Apgar score was 5 points at 1 min and 8 points at 5 min. The latex-specific IgE of this patient was high and IgE for banana, avocado and kiwi were also positive. These foods showed cross-reactions with latex, but she had no history of allergic reactions against these foods. She had a history of atopic reactions and of atopic dermatitis while working as a nurse at the ICU. It is thought that this patient was in the high-risk group.

Association of Replication Error Positive Phenotype with Lymphocyte Infiltration in Endometrial Cancers

Microsatellite instability (MI) has been detected in certain sporadic cancers as well as in hereditary non‐polyposis colorectal cancer (HNPCC). In order to determine the precise clinicopathological characteristics of MI in endometrial cancer, we examined 90 sporadic endometrial cancers (83 endometrioid adenocarcinomas, 3 adenosquamous carcinomas, 3 papillary serous carcinomas, and 1 clear cell carcinoma) and eight lesions of endometrial hyperplasia for replication error (RER) using polymerase chain reaction amplification of CA repeated microsatellite sequences at 15 loci. RER was observed in 23 (28%) of the 83 endometrioid adenocarcinomas at at least one locus and in 19 (23%) at two or more loci (RER+ phenotype) in the seven most commonly observed loci, but not in carcinomas of other histological types or in endometrial hyperplasia. Lymphocyte infiltration around carcinoma cells, which is one of the histological features seen in tumors from HNPCC, was severer in RER+ phenotype tumors (79%, 11/14) than in the RER– tumors (25%, 11/44) (marked/moderate infiltration versus slight, P<0.001, χ2 test), when 58 tumors with muscular invasion were examined. The RER+ phenotype was associated with a higher parity and gravidity (P<0.05, Wilcoxon test). However, RER+ phenotype was not associated with tumor stage, histological grade, muscular invasion, lymph node metastasis or patient survival. In conclusion, MI occurs in a subset of endometrial cancers, which often show marked infiltration of lymphocytes around the tumor.

Immune activation during the implantation phase causes preeclampsia-like symptoms via the CD40–CD40 ligand pathway in pregnant mice

The CD40 ligand (CD40L) is expressed by T cells and has a critical role in immune system regulation. Interventions targeting CD40L interactions following embryo implantation represent an approach to preventing preeclampsia (PE). To better understand the role of CD40L in PE, we developed a PE mouse model in which we examined how CD40L-induced immune activation affects embryo implantation. Blastocysts were incubated with CD40L-expressing adenovirus and then were transferred into the uterine horns of pseudopregnant ICR mice. Histology, biochemistry and flow cytometry experiments were performed to examine the characteristics of the mouse model. In early pregnancy, decidualization and spiral artery remodeling were reduced in CD40L-transfected mice (CD40L mice) compared with control mice. Hematoxylin–eosin (HE) staining revealed hemorrhaging and excess fibrin deposition at the labyrinth layer-junctional zone interface of the placenta, and PAS staining demonstrated prominent focal and segmental sclerosis with collapsed glomerular capillaries in the kidneys of the CD40L mice. Flow cytometry data showed that interferon-γ production derived from CD4+ T cells was elevated in the splenic cells of CD40L mice. Blood pressure (measured by the tail-cuff method) and urine albumin concentrations were significantly increased in CD40L mice compared with control mice. Furthermore, the plasma concentrations of soluble Flt-1 and soluble endoglin were increased in CD40L mice, as occurs in human patients with PE. Thus, CD40L-induced T-helper cell type 1 differentiation during embryo implantation may have a critical role in the pathogenesis of a PE-like presentation in a novel mouse model of PE.

Periodic size changes in a supernumerary ovary with associated corpus luteal cyst

Supernumerary ovaries are extremely rare. Herein is reported a case of supernumerary ovary detected in a 31‐year‐old woman who complained of lower abdominal pain on her left side. Ultrasonography indicated a cystic mass in the pelvis, the size of which fluctuated periodically. A laparotomy was performed and indicated two normal ovaries in addition to a cystic mass in the cul‐de‐sac. Histology of the mass confirmed the presence of both normal ovarian tissue and cystic corpus luteal tissue consistent with the presence of a supernumerary ovary. Examination of the patients medical history suggested that the supernumerary ovary was likely to be of embryonic origin, and not caused by surgical treatment or inflammation. This is the first report of a supernumerary ovary that was associated with periodic episodes of pain and changes in size, and a giant corpus luteal cyst near the rectum.

Atypical carcinoid of the uterine cervix with aggressive clinical behavior: A case report

Highlights • We herein report a case of a 44-year-old Japanese woman diagnosed with stage IB1 atypical carcinoid of the uterine cervix.• After radical hysterectomy, she developed recurrence with aggressive clinical behavior, resistance to CPT-11 + cisplatin and paclitaxel + CBDCA chemotherapy.

Stromal Cell-Derived Factor-1α Plays a Crucial Role Based on Neuroprotective Role in Neonatal Brain Injury in Rats.

Owing to progress in perinatal medicine, the survival of preterm newborns has markedly increased. However, the incidence of cerebral palsy has risen in association with increased preterm birth. Cerebral palsy is largely caused by cerebral hypoxic ischemia (HI), for which there are no effective medical treatments. We evaluated the effects of stromal cell-derived factor-1α (SDF-1α) on neonatal brain damage in rats. Left common carotid (LCC) arteries of seven-day-old Wistar rat pups were ligated, and animals were exposed to hypoxic gas to cause cerebral HI. Behavioral tests revealed that the memory and spatial perception abilities were disturbed in HI animals, and that SDF-1α treatment improved these cognitive functions. Motor coordination was also impaired after HI but was unimproved by SDF-1α treatment. SDF-1α reduced intracranial inflammation and induced cerebral remyelination, as indicated by the immunohistochemistry results. These data suggest that SDF-1α specifically influences spatial perception abilities in neonatal HI encephalopathy.

A Case Report of a Pregnant Gene Carrier of Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease characterized by degeneration of spinal cord motor neurons, atrophy of skeletal muscles, and generalized weakness. It is caused by gene deletions or other mutations in the survival motor neuron 1 gene on chromosome 5q13. There are three types of SMA. Of these types, SMA type 1 (SMA1) is distinguished by the disease onset before 6 months of age and death within the first two years of life. We report a case study of a pregnant SMA1 gene carrier for whom a prenatal diagnosis was performed. The woman delivered a healthy baby, and she was free of anxiety due to the prenatal diagnosis. The case was a 34-year-old woman with a history of giving birth to children with SMA1(3 gravida 2 para). The first baby was diagnosed with SMA1 and died 9 months later. During her second pregnancy, the fetus was prenatally diagnosed with SMA1, and the parents chose to have an artificial abortion. In her third pregnancy, the fetus was prenatally diagnosed as a gene carrier of SMA1 and was delivered. During her fourth pregnancy, a prenatal diagnosis was performed using amniocentesis after genetic counseling, and the fetus was diagnosed as a gene carrier of SMA1. A 3.310 g female baby was delivered with Apgar scores of 9 at 1 minute and 9 at 5 minutes. When a prenatal diagnosis of SMA is performed, various guidelines should be followed, and the patient should be provided with genetic counseling.

Diagnosis and treatment of Wunderlich syndrome

Wunderlich syndrome is a rare Mullerian anomaly consisting of uterine didelphy, cervical cyst, and ipsilateral renal agenesis [1]. It is likely that the malformations occur from embryonic arrest at 8 weeks of gestation, at which point the adjacent Mullerian and metanephric ducts are simultaneously affected. This anomaly inhibits the outflow of menstruation and causes menstrual blood to pool in the uterus; however, it is often asymptomatic anddifficult to diagnose [2]. A healthy 15-year-old female who had experienced normal pubertal events underwent menarche. Three months after menarche, she complained of lower abdominal pain, especially after menstruation. She was of moderate stature, with normal external genitalia, and a regular menstrual cycle. She was diagnosed by magnetic resonance imaging (MRI) as having a double uterus with a right cervical cyst (Fig. 1). Intravenous pyelography demonstrated right renal agenesis with normal function and contour of the left renal collecting system (Fig. 1). The left cervix was intact and the right cystic wall was resected using an ultrasonic cutting and coagulating surgical device (Harmonic scalpel; Johnson & Johnson, New Brunswick, NJ, USA). She was diagnosed with Wunderlich syndrome since the resected tissue demonstrated cervical glands. The postoperative course was uneventful. A healthy 18-year-old female complained of intermittent purulent vaginal discharge since menarche. She underwent menarche at the age of 12 years and experienced normal pubertal events. She had a history of regular menses with increasing lower abdominal pain lasting 2–4 days during each menstrual cycle. She was ofmoderate stature with normal external genitalia. Abdominal ultrasonography demonstrated a small pelvic cystic mass; MRI demonstrated uterus didelphys with a left cervical cyst containing homogeneous fluid compatible with old blood. Intravenous pyelography demonstrated left renal agenesis. The left cystic wall was resectedusinganultrasonic cutting andcoagulating surgical device, andWunderlich syndromewas diagnosed. The postoperative period was uneventful. Hematocervix of Wunderlich syndrome is diagnosed when the ipsilateral hemiuterus and vagina are not connected. Differential diagnosis includes Herlyn–Werner syndrome, which consists of a renal agenesis and an ipsilateral blind hemivagina [3]. Gartners cysts of Herlyn–Werner syndrome can be pathologically differentiated from cervical cysts of Wunderlich syndrome. A Gartners cyst is a cystic remnant of the mesonephric ducts in the vaginal wall, while a cervical cyst demonstrates cervical glands. Common clinical presentations of both Herlyn–Werner syndrome and Wunderlich syndrome are pelvic pain and/or dysmenorrhea shortly after menarche, in association with a vaginal/pelvic mass. When the cyst and vagina are connected, symptoms of abnormal vaginal discharge and bleeding are common. Abdominal and pelvic MRI studies are necessary to confirm and characterize thedetails of uterinemalformation and renal anomaly. Treatment is to resect as much of the obstructing vaginal septum as possible. Errors in surgical management can occur when the diagnosis is incorrect, and laparotomy is performed to explore and resect the intra-abdominal mass. Although fertility is not compromised, spontaneous abortion rate is high. However, patients who carry pregnancy to term often have no obstetric difficulties. Prompt and accurate diagnosis, and subsequent excision of the obstructing vaginal septum, is required in patients with ⁎ Corresponding author. Ehime University School of Medicine, Shitsukawa, Toon, Ehime 791 0295, Japan. Tel.: +81 89 960 5379; fax: +81 89 960 5381. E-mail address: takeyu@m.ehime-u.ac.jp (Y. Matsubara).

Assessment of laparoscopic training for gynecological malignancies using Thiel‑embalmed human cadavers

The introduction of laparoscopic surgery has also been beneficial for patients with gynecological malignancies. In this respect, surgeons should receive related training in the context of human resource development. Hands-on training was introduced using Thiel-embalmed human cadavers (THCs) in 2014. To determine the usefulness of THCs, they were evaluated in terms of tissue color, consistency and operative tactility, among others, compared with in vivo laparoscopic training for gynecological malignancies. Hands-on training sessions using THCs were held for a total of 11 times at Ehime University Graduate School of Medicine between March 2014 and October 2017. Training on THCs included advanced laparoscopic procedures for radical hysterectomy type III. At the end of each training session, data were collected using a standardized, anonymous questionnaire termed the Likert scale. THCs ensured flexibility and plasticity of tissues and organs; therefore, the working space was similar to that in the living body under pneumoperitoneum. After analyzing the quality and consistency of tissue and organ color compared with in vivo conditions, most of the participants agreed or strongly agreed regarding the uterus, adnexa and ureter, but not regarding the large blood vessels. The highest scores were observed in the authenticity of the anatomical condition of each organ. Most participants strongly agreed that training using THCs would help improve their laparoscopic skills with a high level of satisfaction. Furthermore, most participants reported that they would recommend this training to other obstetrician-gynecologists. Laparoscopic training for gynecological malignancies using THCs was comparable to the in vivo conditions in terms of surgical view and operative tactility. Therefore, THCs may be an excellent training tool for improving laparoscopic surgical skills for gynecological malignancies.