Hes1 Increases the Invasion Ability of Colorectal Cancer Cells via the STAT3-MMP14 Pathway.

The Notch pathway contributes to self-renewal of tumor-initiating cell and inhibition of normal colonic epithelial cell differentiation. Deregulated expression of Notch1 and Jagged1 is observed in colorectal cancer. Hairy/enhancer of split (HES) family, the most characterized targets of Notch, involved in the development of many cancers. In this study, we explored the role of Hes1 in the tumorigenesis of colorectal cancer. Knocking down Hes1 induced CRC cell senescence and decreased the invasion ability, whereas over-expression of Hes1 increased STAT3 phosphorylation activity and up-regulated MMP14 protein level. We further explored the expression of Hes1 in human colorectal cancer and found high Hes1 mRNA expression is associated with poor prognosis in CRC patients. These findings suggest that Hes1 regulates the invasion ability through the STAT3-MMP14 pathway in CRC cells and high Hes1 expression is a predictor of poor prognosis of CRC.

Placenta growth factor expression is correlated with survival of patients with colorectal cancer.

BACKGROUND: Overexpression of vascular endothelial growth factor (VEGF) correlates with vascularity, metastasis, and proliferation in colorectal cancer but the role of its homologue, placenta growth factor (PlGF), is unknown. The aim of this study was to evaluate expression and clinical implications of PlGF in colorectal cancer. METHODS: We investigated 74 tumour/non-tumour pairs of colorectal cryosections. Clinical staging was based on the UICC-TNM classification. Expression levels of mRNA for PlGF and VEGF were analysed with quantitative real time reverse transcription-polymerase chain reaction. Proteins were analysed by immunohistochemical staining and enzyme linked immunoabsorbant assay. Analysis of the differences in PlGF and VEGF levels between tumour and non-tumour tissues in the same patient were performed by paired t test; differences between localised and advanced disease patients by the Mann-Whitney, chi(2), and Fisher's exact tests and survival curves by the Kaplan-Meier method. RESULTS: Expression levels for both growth factors were significantly higher in tumour than in non-tumour tissues (p

Calreticulin expression in neuroblastoma--a novel independent prognostic factor.

BACKGROUND: Calreticulin (CRT), an endoplasmic reticulum protein, has been reported to be essential for the differentiation of neuroblastoma (NB) cells, suggesting that CRT may affect the tumor behavior of neuroblastoma. The aim of this study was to evaluate the association of clinicopathologic factors and patient survival with the expression of CRT in patients with NB. PATIENTS AND METHODS: Sixty-eight NBs were investigated by immunohistochemical staining against CRT, and were divided into positive and negative immunostaining groups. Correlations between calreticulin expression, various clinicopathologic and biologic factors, and patient survival were studied. In seven tumor samples, CRT mRNAs and proteins were evaluated with real-time PCR and western blot, respectively, and correlated with immunohistochemical findings. RESULTS: Among 68 NBs, 32 (47.1%) showed positive CRT expression. Positive CRT immunostaining strongly correlated with differentiated histologies, as well as known favorable prognostic factors such as detected from mass screening, younger age (< or =1 year) at diagnosis and early clinical stages, but inversely correlated with MYCN amplification. Kaplan-Meier analysis revealed that NB patients with CRT expression did have better survival. Multivariate analysis demonstrated CRT expression to be an independent prognostic factor. Moreover, CRT expression also predicted better survival in patients with advanced-stage NBs, and its absence predicted poorer survival in patients whose tumor had no MYCN amplification. The amount of CRT mRNAs and proteins in NB tumor samples tested correlated well with the immunohistochemical expressions. CONCLUSIONS: CRT expression correlates with the differentiation of NB and predicts favorable survival, thereby suggesting CRT to be a useful indicator for planning treatment of NB.

Recurrence of intussusception in childhood.

Intussusception is the most common cause of intestinal obstruction between 3 months and 6 years of age. Recurrence after reduction of intussusception in childhood is not rare. To assess the incidence and determinants of recurrence of intussusception in childhood, we conducted a prospective observation in an emergency service of a large referral center during a four-year period. We encountered 89 cases with intussusception of whom nine cases (10.1%) had episodes of recurrent intussusception. Five patients had a single recurrence, three had double recurrence and one had triple recurrence. Age of first intussusception, sex, or concurrent adenovirus infection was not related to the recurrence. None of the 27 patients who needed operative reduction had recurrence, while 9 of 62 patients who were reduced successfully by barium enema developed recurrence (P = 0.05). Compared with the first episode, significantly less vomiting, rectal bleeding and shorter duration of abdominal pain or irritable crying were noted during recurrent episodes. All the recurrent episodes were reduced successfully by barium enema. We conclude that recurrent intussusception in childhood tends to be diagnosed earlier than previous episodes and treated successfully by hydrostatic reduction without complication. Surgical reduction of recurrent intussusception may be reserved for cases of failure of hydrostatic reduction, positive peritoneal sign or existence of pathological lead point because of favorable response to barium reduction. Recurrent intussusception seldom occurs in patients who underwent surgical reduction.

Prognostic indicators of survival in infants with congenital diaphragmatic hernia.

PURPOSE: This study sought to identify the factors predictive of the short-term outcome in infants with congenital diaphragmatic hernia (CDH). METHODS: We retrospectively reviewed medical records from September 1985 to December 1998 for all infants born with CDH and managed at National Taiwan University Hospital (NTUH). Coexisting pathology and measures of respiratory function were analyzed to determine the prognostic factors. RESULTS: A total of 32 infants with CDH were managed at NTUH over the past 13 years. The investigated factors associated with poor prognosis in CDH included congenital heart disease, chromosomal abnormality, pneumothorax, and preoperative parameters including arterial partial carbon dioxide pressure greater than 40 mmHg, arterial partial oxygen pressure less than 100 mmHg, alveolo-arterial partial oxygen pressure greater than 610 mmHg, and oxygen index (OI) greater than 0.4. Multiple logistic regression analyses indicated that only an OI greater than 0.4 and pneumothorax were significant indicators of poor prognosis. When the incidence of pneumothorax was compared between patients who received ventilation using a conventional mechanical ventilator or high-frequency oscillatory ventilator (HFOV), a trend toward a lower incidence of pneumothorax in those using HFOV for initial stabilization was found (p = 0.08). CONCLUSIONS: An OI greater than 0.4 before surgery and pneumothorax are poor prognostic indicators in infants with CDH. A high OI is reflective of the severity of pulmonary dysfunction in infants. Pneumothorax further compromises the dysfunction of a hypoplastic lung in infants with CDH. The results of this study show the importance of avoiding iatrogenic pneumothorax during management of infants with CDH.

Paraplegia: complication of percutaneous central venous line malposition.

Percutaneously inserted central venous lines are usually a safe and effective means of securing prolonged central venous access but can have serious complications. One patient who experienced clinically important morbidity related to inadvertent malpositioning of a central venous catheter is described. It was inserted via the left saphenous vein into the lumbar venous plexus and resulted in milky cerebrospinal fluid, urine retention, and paraplegia. Reviewing the literature, only 11 patients with the same malposition were reported, three of them with percutaneously inserted central venous lines. In these three patients and our patient the left saphenous vein was used. Neurologic sequelae of paraplegia and urine retention were recorded in 25% (3/12) of patients. The mortality rate approached 42% (5/12) but only two patients were related to catheter misplacement. Although the complication rate is extremely low and difficult to recognize, catheter malposition into the ascending lumbar vein can lead to lethal complications.

Antenatal diagnosis of congenital hepatoblastoma in utero.

A fetus with a huge hepatic tumor was detected by sonography at 36 weeks of gestation. The mass appeared as a single, solid and polylobular tumor located in the right lobe of the liver. Foci of hemorrhage, necrosis and some tiny calcifications were seen. The adjacent right kidney appeared normal but was displaced. The right adrenal gland was not visualized. Three-dimensional power Doppler sonography further depicted the corresponding vascular anatomy of the tumor, including its vascularization pattern and blood supply. The tumor was situated to the right of the umbilical vein and portal sinus, possibly deriving its blood supply from the portal circulation. The fundamental findings suggested the diagnosis of hepatoblastoma by exclusion of other possibilities. The baby was delivered by Cesarean section at 36 weeks' gestation, due to signs of fetal distress. Unfortunately, hypotension, tachycardia, and tachypnea developed shortly after birth. Surgical intervention was performed, but intractable bleeding occurred intra-operatively. The infant died at 6 days of age. Autopsy confirmed the diagnosis of hepatoblastoma. We believe this is the first reported case of the antenatal diagnosis of congenital hepatoblastoma.

Comparison of serum specific IgE antibodies to staphylococcal enterotoxins between atopic children with and without atopic dermatitis.

BACKGROUND: The skin of patients with atopic dermatitis (AD) exhibits a striking susceptibility to colonization and infection by Staphylococcus aureus. The exotoxins secreted by S. aureus can act as superantigens and classic allergens, inducing the production of functionally relevant specific IgE antibodies. The aim of this study was to compare the levels and positive rates of serum staphylococcal enterotoxin A (SEA)- and staphylococcal enterotoxin B (SEB)-specific IgE between atopic children with and without AD. METHODS: Sixty children with AD, 55 children with respiratory allergy without AD, and 24 nonatopic healthy children were studied. The levels and positive rates of serum SEA- and SEB-specific IgE were compared among three groups. The correlation between the levels or positive rates of serum SEA/SEB-specific IgE and the severity of AD or the presence of previous skin infections was studied. RESULTS: The children with AD had significantly higher levels and positive rates of serum SEA- and SEB-specific IgE than the atopic children without AD (P < 0.001) and the nonatopic children (P < 0.001). There was no significant difference in the levels and positive rates of serum SEA- and SEB-specific IgE between the atopic children without AD and the nonatopic children. With or without adjustment for the potential confounding effect of total serum IgE levels, the levels and positive rates of serum SEA- and SEB-specific IgE were significantly correlated with severity of AD (P <0.005), but they were not significantly different between AD children with and without previous skin infections. CONCLUSIONS: SEA and SEB may contribute to chronic inflammation and exacerbation of AD through the IgE-mediated immune response.

Congenital intracranial teratoma.

Congenital intracranial teratoma is a rare disease. A fetus with a congenital intracranial teratoma presenting with a disproportionately enlarged head at 27 weeks gestation is presented. Prenatal ultrasonography and fetal magnetic resonance imaging demonstrate a huge, heterogenous intracranial mass in the left supratentorial region, with the left cerebral hemisphere being compressed and flattened. The infant died of respiratory failure within 24 hours of birth at 28 weeks gestation. On postmortem examination the histologic report revealed an immature teratoma. Fetal MRI is helpful in the prenatal diagnosis and evaluation of intracranial tumor.

Power Doppler ultrasound imaging in neonatal cerebral venous sinus thrombosis.

Neonatal sinus thrombosis is a rare occurrence in sick neonates. Because of its nonspecific manifestations, the incidence is underestimated. This disease may not be demonstrated by conventional color Doppler and is diagnosed by computed tomography or magnetic resonance imaging. The authors report a neonate with neonatal sinus thrombosis diagnosed by power Doppler and suggest that the technique may be used as a less expensive and more available screening and follow-up method in high-risk neonates.

3-D power Doppler cerebral angiography in neonates and young infants: comparison with 2-D power Doppler angiography.

The aims of this study were to evaluate the ability of 3-dimensional (3-D) power Doppler angiography (3DPDA) to depict the intracranial vasculature in infants, to compare with 2-D power Doppler ultrasonography (2DPDU), and to explore the potential clinical applications of this procedure in young infants with brain disorders. We performed 3DPDA in 27 infants. 2DPDU were completed in both sagittal and coronal directions in 12 of these patients. In the other 15, only right sagittal plane images were available for comparison. Using a grading system and with only vessels with more than half of the length demonstrated included for comparison, we compared the Doppler signals of major vessels. 3DPDA could have good visualization in more than 60% of the internal carotid artery, ophthalmic artery, pericallosal artery, callosomarginal artery, internal cerebral vein, vein of Galen, and straight sinus in the sagittal plane. 3DPDA also could have good demonstration in about 50% of basilar artery in coronal plane, and posterior communicating artery, posterior cerebral artery, and lenticulostriate artery in sagittal plane. 3DPDA was better than 2DPDU in demonstrating all the major intracranial vessels in different planes, except the anterior communicating artery. In the anterior communicating artery, neither can demonstrate more than 30%.

Granulocyte colony-stimulating factor in the cord blood of premature neonates born to mothers with pregnancy-induced hypertension.

OBJECTIVES: To estimate the cord blood levels of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in preterm infants and to study the relationship of these levels to pregnancy-induced hypertension (PIH) and absolute neutrophil counts. STUDY DESIGN: G-CSF and GM-CSF levels in the cord blood of preterm neonates (n = 74) either with or without maternal PIH were estimated by enzyme-linked immunosorbent assay. RESULTS: Infants in the PIH group had lower white blood cell, absolute neutrophil, absolute lymphocyte, and monocyte counts. The levels of G-CSF in cord blood were significantly lower in infants whose mothers had PIH (P =.04) and in infants with neutropenia (P =. 01). G-CSF levels were positively correlated with both absolute neutrophil count (P =.02) and total white blood cell count (P =.01). GM-CSF was undetectable in all subjects. According to logistic regression with neutropenia as the dependent variable, only maternal PIH (P <.001), gestational age (P <.001), and G-CSF (P =.01) were independently related. CONCLUSION: In this study maternal PIH and low gestational age were significantly associated with neutropenia in premature infants. Low G-CSF levels may contribute to the neutropenia that is commonly seen in infants born to mothers with PIH.

Longitudinal study of serum free thyroxine and thyrotropin levels by chemiluminescent immunoassay during infancy.

From October 1996 to December 1997, ninety normal infants born at full-term were enrolled in this study. There were 59 female infants and 31 male infants. Both serum free thyroxine and thyrotropin levels were measured by chemiluminescent immunoassay in the first week (n = 75), 3 months (n = 66), 6 months (n = 79), and 12 months (n = 77) of age. Serum free thyroxine levels (ng/dL) (mean +/- standard deviation) were 2.2 +/- 0.5, 1.3 +/- 0.2, 1.2 +/- 0.2, 1.0 +/- 0.2 for each age group, respectively. Serum thyrotropin levels (mIU/L) (mean +/- standard deviation) were 9.7 +/- 6.7, 3.0 +/- 1.6, 2.7 +/- 1.3, 2.5 +/- 1.2 for each age group, respectively. There was no significant difference between the levels of these two parameters between male and female. The present study provides the reference data for the normal range of thyroid function during infancy. Our results also show that the serum free T4 and TSH levels tend to decline during the first year of life.

Comparison of the outcome of extremely-low-birth-weight infants between two periods.

A comparison was made of the outcome of 73 neonates born with their birth weight of 500-999 gm in National Taiwan University Hospital during the period between January 1, 1993 and December 31, 1996 (Period II), with the outcome of 21 such neonates born between April 1, 1988 and October 31, 1992 (Period I). Exclusion criteria included parental refusal for resuscitation, and major anomalies. Data were collected via a predetermined record sheet. The incidences of the extremely-low-birth-weight infants were 23/10,173 (0.23%) and 81/13,835 (0.59%) in Periods I and II, respectively. Early neonatal mortality rate was significant decreased in Period II (43% versus 14%). The limit of viability was improved from gestational age of 26 weeks or 700 gm to gestational age of 24 weeks or 600 gm. The incidence of neonatal morbidity (80% versus 50%) and total survival rate (48% versus 60%) have not changed significantly as seen in this limited number of cases. This study concluded that, with the introduction of exogenous surfactant and modern neonatal care, early neonatal survival rate and the limit of viability were improved.

Early outcome of extremely low birth weight infants in Taiwan.

We retrospectively evaluated the outcome and the risk factors for mortality among extremely low birth weight (ELBW) infants born at National Taiwan University Hospital. The records of all live-born infants with body birth weight of less than 1,000 g from January 1, 1993, to December 31, 1996, were evaluated. Infants with major anomalies or whose parents refused resuscitation were excluded from the analysis. There were 81 ELBW infants (0.59%) among a total of 13,835 live births during the study period, and 73 cases were enrolled for study. The mean gestational age (GA) was 27.2 (range, 24-34) weeks. Sixty-six percent of the ELBW infants were born by cesarean delivery. Respiratory distress syndrome occurred in 64% of infants and exogenous surfactant therapy was given to 47%, while intermittent mandatory ventilation was given to 85%. Symptomatic patent ductus arteriosus occurred in 34% of infants, septicemia in 30%, chronic lung disease in 48%, grade III to IV intraventricular hemorrhage in 27%, stage III to V retinopathy of prematurity in 33%, and necrotizing enterocolitis in 8%. Neonatal survival was 74%, survival to discharge was 60%, and intact survival was 50%. The survival rate was 40% for infants with a birth body of weight less than or equal to 750 g, and 68% for those with a birth body weight of greater than 750 g. While survival was 27% for infants with a GA of less than 26 weeks, it was 75% for those with a GA of greater than or equal to 26 weeks. The survival rate improved year by year for those with a GA less than 28 weeks. Cox regression analysis of survival showed that Apgar score at 1 minute (p = 0.0063), pulmonary hypertension (p = 0.012), and severe intraventricular hemorrhage (p = 0.0031) were the most important factors associated with mortality. Though the outcome of ELBW infants in our institute seems poorer than in some more developed countries, it is improving. The prognosis for ELBW infants of 24 to 25 weeks' GA remains guarded under our present care.

PIP: A review of the records of all live-born neonates with a birth weight below 1000 g born in 1993-96 at National Taiwan University Hospital was conducted, with emphasis on outcomes and risk factors for mortality. There were 81 extremely-low-birth-weight infants (0.59%) among the 13,835 live births recorded during the 3-year study period and, after exclusion of infants with major anomalies, 73 cases were enrolled for study. The mean gestational age was 27.2 weeks (range, 24-34 weeks). The most common complications of pregnancy leading to premature delivery were antepartum hemorrhage (44%) and pregnancy-induced hypertension. Respiratory distress syndrome occurred in 64%; exogenous surfactant therapy was provided to 47% and 85% received intermittent mandatory ventilation. Symptomatic patent ductus arteriosus occurred in 34% of infants, septicemia in 30%, chronic lung disease in 48%, grade III-IV intraventricular hemorrhage in 27%, stage III-V retinopathy of prematurity in 33%, and necrotizing enterocolitis in 8%. 54 infants (74%) survived the neonatal period and 44 (60.3%) survived until discharge. The survival rate was 40% for infants with a birth weight of 501-750 g and 68% for those weighing 751-999 g. Survival was 27% for infants with a gestational age under 26 weeks compared with 75% for those with a gestational age of 26 weeks and above. Cox regression analysis of survival indicated that Apgar scores at 1 minute, pulmonary hypertension, and severe intraventricular hemorrhage were the most significant contributing factors to mortality.

Camptomelic dysplasia: report of one case.

A typical case of camptomelic dysplasia was noted to have only prenatally bowed legs. The infant showed the following characteristic features: dolichocephaly, flat-appearing small face, low nasal bridge, micrognathia, cleft palate, anterior bowing of tibia with skin dimpling over convex surface, mild bowing of femurs, talipes equinovarus, and tracheomalacia. Because of poor prognosis, the parents decided not to resuscitate the baby aggressively and the baby died of respiratory failure at six days old. Although this disease is rare, it does happen in ethnic Chinese and, because it may be an inherited disease, a correct diagnosis for camptomelic dysplasia is very important.

Nonprogressive congenital unilateral ventriculomegaly.

Congenital unilateral ventriculomegaly is a rare condition, usually caused by obstruction of the foramen of Monro. In the past, this condition required surgical intervention. We present a female newborn with nonprogressive unilateral ventriculomegaly which was initially detected by prenatal sonography. No surgical intervention was performed, and during the 9 months of follow-up, she had normal head growth and reached appropriate developmental milestones.