Contrasting Prognostic Effects of Tumor-Infiltrating Lymphocyte Density in Cardia and Non-cardia Gastric Adenocarcinomas

Purpose@#This study sought to investigate the prognostic significance of tumor-infiltrating lymphocytes (TILs) in relation to tumor location within the stomach. @*Materials and Methods@#The densities and prognostic significance of TIL subsets were evaluated in 542 gastric cancer patients who underwent gastrectomy. Immunohistochemical staining for CD3, CD4, CD8, forkhead/winged helix transcription factor (Foxp3), and granzyme B was performed. @*Results@#Cardia cancer was associated with significantly lower densities of CD8 T-cells and higher densities of Foxp3 and granzyme B T-cells than non-cardia tumors. Multivariate analysis showed that advanced age (hazard ratio [HR], 1.023; 95% confidence interval [CI], 1.006–1.040), advanced T classification (HR, 2.029; 95% CI, 1.106–3.721), lymph node metastasis (HR, 3.319; 95% CI, 1.947–5.658), low CD3 expression (HR, 0.997; 95% CI, 0.994–0.999), and a high Foxp3/CD4 ratio (HR, 1.007; 95% CI, 1.001–1.012) were independent predictors of poor overall survival in cardia cancer patients. In non-cardia cancer patients, total gastrectomy (HR, 2.147; 95% CI, 1.507–3.059), advanced T classification (HR, 2.158; 95% CI, 1.425–3.266), lymph node metastasis (HR, 1.854; 95% CI, 1.250–2.750), and a low Foxp3/CD4 ratio (HR, 0.978; 95% CI, 0.959–0.997) were poor prognostic factors for survival. @*Conclusions@#The densities and prognostic effects of TILs differed in relation to the location of tumors within the stomach. The contrasting prognostic effects of Foxp3/CD4 ratio in cardia and non-cardia gastric cancer patients suggests that clinicians ought to consider tumor location when determining treatment strategies.

Comparison of Four Pancreatic Islet Implantation Sites

Although the liver is the most common site for pancreatic islet transplantation, it is not optimal. We compared kidney, liver, muscle, and omentum as transplantation sites with regard to operative feasibility, and the efficiency of implantation and glycemic control. Islets from C57BL/6 mice were transplanted into diabetic syngeneic recipients. The mean operative time and mortality were measured to assess feasibility. To assess implantation efficiency, the marginal mass required to cure diabetes and the mean time taken to achieve normoglycemia were measured. A glucose tolerance test was performed to assess glycemic control efficiency. The data are listed in the order of the kidney, liver, muscle, and omentum, respectively. The mean mortality rate was 6.7, 20.0, 7.1, and 12.5%; the mean operative time was 10.2, 27.4, 11.2, and 19.8 min; the marginal islet mass was 100, 600, 600, and 200 islet equivalence units and the mean time to reach euglycemia was 3.0, 15.1, 26.6, and 13.9 days. The glucose kinetics of omental pouch islets was the most similar to controls. Thus, a strategic approach is required for deciding on the best transplantation recipient sites after considering donor sources and islet volume. Alternatives can be chosen based on safety or efficacy.

Outcomes of Palivizumab Prophylaxis for Respiratory Syncytial Virus Infection in Preterm Children with Bronchopulmonary Dysplasia at a Single Hospital in Korea from 2005 to 2009

This study was performed to evaluate the utilization and outcomes of palivizumab in high risk children born prematurely with chronic lung disease (CLD). A retrospective review of 128 patients was conducted from September 2004 to March 2009 at the Ajou University Hospital. All patients were diagnosed with CLD, were born at < or =35 weeks of gestation, were <2 yr old at the onset of respiratory syncytial virus (RSV) season, and had received medical therapy within six months prior to the RSV season. Fifty-three patients did not receive palivizumab prophylaxis and 75 patients received at least one dose of palivizumab. There were no statistically significant differences between the patients with and without palivizumab prophylaxis with regard to demographic characteristics and risk factors for RSV infection. There were no systemic adverse responses. Compliance with the course of prophylaxis was 92.2%. Hospitalization associated with RSV occurred in 12 cases (22.6%) in the group without prophylaxis and in three cases (4.0%) with prophylaxis. Palivizumab prophylaxis significantly reduced the frequency of RSV-related hospitalization in preterm children with CLD. This is the first retrospective review of palivizumab prophylaxis in Korea. Palivizumab is effective and well tolerated in high risk prematurely born children.

De Novo Pericentric Inversion of Chromosome 9 in Congenital Anomaly

PURPOSE: The pericentric inversion of chromosome 9 is one of the most common structural balanced chromosomal variations and has been found in both normal populations and patients with various abnormal phenotypes and diseases. The aim of this study was to re-evaluate the clinical impact of inv(9)(p11q13). MATERIALS AND METHODS: We studied the karyotypes of 431 neonates with congenital anomalies at the Pediatric Clinic in Ajou University Hospital between 2004 and 2008 and retrospectively reviewed their clinical data. RESULTS: Chromosomal aberrations were detected in 60 patients (13.9%). The most common type of structural abnormality was inv(9)(p11q13), found in eight patients. Clinical investigation revealed that all eight cases with inv(9)(p11q13) had various congenital anomalies including: polydactyly, club foot, microtia, deafness, asymmetric face, giant Meckel's diverticulum, duodenal diaphragm, small bowel malrotation, pulmonary stenosis, cardiomyopathy, arrhythmia, and intrauterine growth restriction. The cytogenetic analysis of parents showed that all of the cases were de novo heterozygous inv(9)(p11q13). CONCLUSION: Since our results indicate that the incidence of inv(9)(p11q13) in patients with congenital anomalies was not significantly different from the normal population, inv(9)(p11q13) does not appear to be pathogenic with regard to the congenital anomalies. Some other, to date unknown, causes of the anomalies remain to be identified.

A Korean Family with the Muenke Syndrome

The Muenke syndrome (MS) is characterized by unicoronal or bicoronal craniosynostosis, midfacial hypoplasia, ocular hypertelorism, and a variety of minor abnormalities associated with a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene. The birth prevalence is approximately one in 10,000 live births, accounting for 8-10% of patients with coronal synostosis. Although MS is a relatively common diagnosis in patients with craniosynostosis syndromes, with autosomal dominant inheritance, there has been no report of MS, in an affected Korean family with typical cephalo-facial morphology that has been confirmed by molecular studies. Here, we report a familial case of MS in a female patient with a Pro250Arg mutation in exon 7 (IgII-IGIII linker domain) of the FGFR3 gene. This patient had mild midfacial hypoplasia, hypertelorism, downslanting palpebral fissures, a beak shaped nose, plagio-brachycephaly, and mild neurodevelopmental delay. The same mutation was confirmed in the patient's mother, two of the mother's sisters and the maternal grandfather. The severity of the cephalo-facial anomalies was variable among these family members.

Anticonvulsant Therapy in Neonate

The immature neonatal brain is susceptible to the development of seizures. Seizures occur in 1% to 5% of infants during the neonatal period. Neonatal seizures are most commonly associated with serious acute illnesses, such as hypoxic-ischemic encephalopathy, birth trauma, metabolic disturbances, or infections. Thus, newborn infants with seizures are at risk for neonatal death and survivors are at risk for neurologic impairment, developmental delay, and subsequent epilepsy. Experimental data have also raised concerns about the potential adverse effects of the currently used anticonvulsants in neonates on brain development. Therefore, in the management of neonatal seizures, confirmatory diagnosis and optimal, but shorter, duration of anticonvulsant therapy is essential. Nevertheless, there has been substantial progress in understanding the developmental mechanisms that influence seizure generation and responsiveness to anticonvulsants. The currently used therapies have limited efficacy and the treatment of neonatal seizures has not significantly changed in the past several decades, This review includes an overview of current approaches to the treatment of neonatal seizures.

Clinical and Biochemical Factors Associated with GnRH Stimulation test in the Idiopathic Central Precocious Puberty and Early Puberty Girls / 대한소아내분비학회지

PURPOSE: Gonadotropin releasing hormone (GnRH) stimulation test is the gold standard method for the diagnosis of central precocious puberty. To predict the result of this test, we studied clinical and biochemical factors associated with the test. METHODS: We evaluated 168 girls under 9 years old with the signs of breast budding and more than one year bone age advancement who underwent this test. We defined the result as two criteria. In the first criteria, positive result of the test means peak LH> or =5 IU/L and peak/basal LH> or =2. In the second criteria, positive result means peak LH> or =5 IU/L, peak/basal LH> or =2 and peak LH/FSH> or =1. RESULTS: In the both first and second criteria, 83 and 31 girls had positive results and other 85 and 137 girls had negative results respectively. In both criteria, the patients with positive results turned out to have more advancement in bone age, smaller predicted adult height, smaller paternal height and higher insulin like growth factor-1 (IGF-1) than those of the patients with negative results. Peak LH was positively correlated with bone age advancement (r=0.35, P<0.001) and IGF-1 (r=0.42, P<0.001) and negatively correlated with predicted adult height (r=-0.22, P=0.01). In multiple logistic regression, bone age was significant predictive factor [first criteria, OR 1.43 (95% CI 1.09, 1.87), P=0.01; second criteria, OR 2.46 (95% CI 1.48, 4.08), P=0.01] of the positive results. CONCLUSION: The result of GnRH stimulation test depends on the degree of breast development and advancement in bone age. Also, IGF-1 is the only positively correlated biochemical factor with the test.

A Congenital Giant Hepatic Hemangioendothelioma Treated with Interferon-alpha and Complete Tumor Resection

Infantile hepatic hemangioendotheliomas (IHHEs) are benign vascular tumors, but can be associated with the life-threatening complications, such as congestive heart failure, disseminated intravascular coagulation, and massive bleeding. Various therapeutic options have been developed and the treatment response depends on the patient's clinical status and the nature of the lesion. In the case of a symptomatic IHHE, a non-invasive and precise diagnosis should be performed promptly before the therapeutic method is chosen. Additionally, it should be kept in mind that the residual lesions have malignant potential. We report a case of a congenital giant IHHE that was successfully reduced in size by interferon-alpha and completely removed by surgical tumor resection with a hepatic lobectomy.

A Case of an Addition of Chromosome 9 Short Arm Associated with Multiple Congenital Anomalies

Human chromosome 9 is characterized by a high degree of morphologic heteromorphisms, including variation in the size of the heterochromatin. We present a case of a de novo short arm addition of chromosome 9, [46, XY, add(9)(p13)], associated with multiple anomalies, including trigonocephaly, upward slant of the palpebral fissures, patent ductus arteriosus, pulmonary hypertension, hypertrophic cardiomyopathy, umbilical hernia, ambiguous genitalia, and sensorineural hearing and visual loss. This mutation affects the pericentric region of the heterochromatin. This patient exhibited a clinically important breakpoint of the heterochromatic region of chromosome 9 short arm and the associated anomalies.

Neonates delivered by vacuum or forceps: Management and outcomes / 대한주산의학회잡지

No abstract available.

Giant Neonatal Hemangioendothelioma of the Liver Diagnosed by 99mTc-RBC Scintigraphy

Infantile hemangioendothelioma (IHE) is a benign tumor of the liver composed of anastomosing vascular channels lined by plump endothelial cells. The major clinical findings of IHE are abdominal mass, hepatomegaly, cutaneous hemangioma, congestive heart failure, anemia and disseminated intravascular coagulopathy. Precise diagnosis of IHE is crucial because medical therapies using steroid and/or interferon can be tried unless there are grave compressive symptoms. Along with CT scan and MRI studies, scintigraphic evaluation with 99mTc-RBC offers an accurate method of identification of these lesions, and allows differentiation from other common primary or secondary hepatic masses. We report two cases of giant IHE of the liver those were diagnosed with 99mTc- RBC scan and confirmed with pathologic evaluation after surgical removal.

An Unbalanced Translocation of Chromosome 16 Associated with Multiple Congenital Anomalies

We present a case of de novo reciprocal unbalanced translocation of chromosome 16, [46, XX, 8p+, der(8)t(8;16)(p23;q13)enh(16)], associated with clinical features, including anal atresia, vertebral anomaly, urogenital anomaly, single umbilical artery, ventricular septal defect and bilateral sensorineural hearing losses.

Effects of Antenatal Administration of Keratinocyte Growth Factor (KGF), Epidermal Growth Factor (EGF), and Dexamethasone on mRNA Levels of Surfactant Proteins in Fetal Mouse Lungs

PURPOSE: Growth factors such as keratinocyte growth factor (KGF) and epidermal growth factor (EGF) have been shown to stimulate alveolar proliferation and pulmonary surfactant production in neonatal animals, raising the question of their antenatal uses. We studied the effects of antenatal administration of recombinant human KGF (rhKGF), recombinant human EGF (rhEGF), or dexamethasone (Dexa) in mouse pups on mRNA synthesis of surfactant proteins A, B, and C. METHODS: Time-dated pregnant mice were divided into 5 groups. At gestational day 16, the pregnant mice received intraperitoneal injection of saline, rhKGF, rhKGF+Dexa, Dexa alone, or rhEGF. Fetuses were delivered by cesarean section 24 h later. Lung tissues were obtained for isolation of RNA and realtime RT-PCR for SP-A, -B, and -C. RESULTS: Relative SP-A mRNA levels of any of the treatment groups were not significantly different from the control group. Either KGF or Dexa group did not show higher levels of SP-B mRNA than control group. Relative mean values of SP-B mRNA of KGF+Dexa and EGF groups were higher than the control group, but not statistically significant. Even though there was a trend of increasing levels of SP-C mRNA in all the treatment groups, the differences were not statistically significant. CONCLUSION: Antenatal intraperitoneal administration of KGF, EGF, or dexamethasone to pregnant mice did not increase the mRNA expressions of surfactant proteins in preterm mouse pups. However, the effects of different doses, timing, and routes of administration are important factors that may influence the outcomes and should further be investigated in the future.

Effects of Maeil Human Milk Fortifier on Growth and Bone Mineralization in Preterm Infants

PURPOSE: A prospective, controlled trial was conducted to evaluate growth, bone mineralization, and nutritional status receiving preterm human milk supplemented with a newly formulated Maeil human milk fortifier. METHODS: Twenty five fortified human milk-fed and preterm formula-fed infants with a birth weight < 1, 800 g and gestational age <35 weeks, who were born at Ajou University Hospital from March, 2003 through August, 2004 were studied. Growth, biochemical indices of bone mineralization, feeding tolerance, morbidity and wrist X-ray were assessed serially. Total body bone mineral density was measured by dual energy X-ray absorptiometry at 2 and 5months of age. RESULTS: There were no differences in growth, including weight, height and head circumference, between two groups. Serum Ca, P, ALP and other biochemical indices were similar. Although low grade rickets (grade I and II) were occasionally found on wrist X-ray, the rate of occurrence and severity were similar. The bone mineral densities of both group showed no difference. CONCLUSION: The fortified human milk-fed infants and preterm formula-fed infants showed no difference in growth, and bone mineralization. This newly formulated Maeil human milk fortifier can be safely used in preterm infants.

The Usefulness of Diffusion: Weighted Magnetic Resonance Image in the Diagnosis of Neonatal Seizure

PURPOSE: Conventional imaging study, such as CT and T1 or T2 weighted MRI, usually give valuable information, but cannot always differentiate early parenchymal lesion in the acute stage of hypoxic-ischemic brain injury from unmyelinated white matter in the neonate. Diffusion-weighted image already has been proven highly sensitive and specific for the detection of acute stroke in adult population. This study was performed to evaluate the usefulness of this technique in the diagnosis of neonatal seizure. METHODS: 11 neonates, aged from 1 to 6 days admitted at Ajou University Hospital for neonatal seizure, were studied with diffusion-weighted imaging and conventional images at within 72 hours of seizure onset. Follow-up MRIs were obtained from 4 patients at about 3 months of age. Comparisons were made among conventional T1, T2 weighted images, diffusion-weighted images and images from follow-up MRIs. RESULTS: 9 of 11 patients showed abnormal findings on diffusion-weighted images, 2 patients showed focal cerebral infarction and 7 patients showed diffuse injury consistent with HIE. Diffusion-weighted image showed more accurate images of involved lesion than T1 or T2 weighted images in some cases. But most of all, diffusion-weighted image could detect lesions of white matter injury which was not visualized on conventional MRI. The white matter injury later result in cortical atrophy and leukomalatic changes by follow-up MRI. CONCLUSION: Our study provides the usefulness of diffusion-weighted imaging in the evaluation of neonatal seizure along with conventional images. For the confirmation, a larger number of infants and clinical evaluation for development will be needed.