Imaging findings of primary hepatic angiosarcoma on gadoxetate disodium-enhanced liver MRI: comparison with hepatic haemangiomas of similar size.

AIM: To describe imaging characteristics of primary hepatic angiosarcoma on gadoxetate disodium-enhanced dynamic magnetic resonance imaging (MRI) and to determine features that differentiate angiosarcomas from similar-sized haemangiomas. MATERIALS AND METHODS: The study included 15 patients with hepatic angiosarcomas and 35 patients with size-matched hepatic haemangiomas who underwent gadoxetate disodium-enhanced liver MRI. The number, size, growth pattern, signal intensity (SI) characteristics, and SI changes on dynamic scans were evaluated and compared between the two entities. RESULTS: Overall, hepatic angiosarcomas significantly more often showed lesion multiplicity (86.7%), capsular retraction (40%), prominent intratumoural vessels (66.7%), vascular invasion (20%), heterogeneous SI on T2-weighted (100%) and hepatobiliary phase images (80%), and intralesional haemorrhage (60%, all p<0.05). On dynamic scans, angiosarcomas demonstrated enhancing foci of irregular or rim-like nodular/linear or bizarre (86.7%) shapes, with centrifugal or bizarre patterns of progressive enhancement (53.3%). Enhancement of angiosarcomas was less than that of the blood pool on visual grading, but the enhancement curves followed that of the aorta. Regardless of size, angiosarcomas showed heterogeneous T2 SI, intratumoural haemorrhage, and heterogeneity during the hepatobiliary phase, whereas these findings were more common in haemangiomas >6 cm in diameter. CONCLUSION: Gadoxetate disodium-enhanced dynamic liver MRI is capable of depicting vascular hallmarks of hepatic angiosarcomas. Heterogeneous SI on T2-weighted and hepatobiliary phase images, multiplicity, and an enhancement curve following that of the aorta are also distinctive features that differentiate angiosarcomas from haemangiomas.

Radiofrequency ablation as an alternative to hepatic resection for single small hepatocellular carcinomas.

BACKGROUND: This study aimed to investigate whether radiofrequency ablation (RFA) is an alternative to surgical resection for hepatocellular carcinoma (HCC) within the context of current guidelines. METHODS: This retrospective study included patients with normal portal pressure and serum bilirubin level who initially underwent liver resection or RFA for a single HCC of maximum size 3 cm. Between-group differences in cumulative rates of survival and recurrence specific for HCC were analysed in the entire cohort and in a propensity score-matched cohort. RESULTS: A total of 604 patients were enrolled, 273 in the liver resection group and 331 in the RFA group. The 5- and 10-year HCC-specific survival rates for the resection and RFA groups were 87·6 versus 82·1 per cent and 59·0 versus 61·2 per cent respectively (P = 0·214), whereas overall 5- and 10-year recurrence-free survival rates for the corresponding groups were 60·6 versus 39·4 per cent and 37·5 versus 25·1 per cent respectively (P < 0·001). In the propensity score-matched cohort (152 pairs), there were no differences in HCC-specific survival (hazard ratio (HR) 1·03 for RFA versus resection; P = 0·899), whereas recurrence-free survival again differed between the treatment groups (HR 1·75; P < 0·001). RFA was independently associated with poorer outcomes in terms of treatment-site recurrence-free survival (adjusted HR 1·66; P = 0·026), but not non-treatment-site recurrence-free survival (adjusted HR 1·15; P = 0·354). CONCLUSION: Although RFA carries a higher risk of treatment-site recurrence than hepatic resection, it provides comparable overall survival in patients with a single small HCC without portal hypertension or a raised bilirubin level.

Parental perceived benefits of OROS-methylphenidate treatment for the child with attention-deficit/hyperactivity disorder and for parents themselves.

Given the shortage of studies on parental perceived benefits of OROS-methylphenidate treatment in Asian populations, we assessed parental response to OROS-methylphenidate treatment of Korean children with attention-deficit/hyperactivity disorder (ADHD), in relation to children's academic performance and behavioral symptoms as well as parental rearing stress and depressive symptoms.We enrolled 132 medication-naïve children with ADHD into a multicenter, open-label, 12-week trial of OROS-MPH. The outcome measures were the ADHD rating scale-IV (ADHD-RS), the comprehensive attention test and academic performance rating scale, and the clinical global impression (CGI)-severity/improvement instrument (for the children) and Beck depression inventory and parenting stress index (for their parents).We found parent-perceived improvements in children's ADHD-related behavioral symptoms and academic function and their parents' depressive symptoms and parenting stress. Investigator-rated ADHD symptoms and subjects' neuropsychological function were also improved (p<0.001).Parents of Korean children with ADHD perceive that OROS-methylphenidate treatment improves their children's academic function and behavior as well as their own child-rearing stress and emotional state. These findings must be interpreted with caution, due to a non-comparative open-label trial.

Glucose as a Risk Factor for Periodontitis in Kidney Transplantation Patients.

BACKGROUND: Various factors including diabetes and oxidative stress are associated with periodontal inflammation. End-stage renal disease causes various systemic abnormalities in patients, including cardiovascular disaese, metabolic abnormalities, and infection. Even after kidney transplantation (KT), these factors are known to be associated with inflammation. Our study, therefore, aimed to study risk factors associated with periodontitis in KT patients. METHODS: Patients who visited Dongsan Hospital, Daegu, Korea since 2018 and have undergone KT were selected. As of November 2021, 923 participants, with full data including hematologic factors were studied. Periodontitis was diagnosed based on residual bone level in panoramic views. Patients were studied by the presence of periodontitis. RESULTS: From 923 KT patients, 30 were diagnosed with periodontal disease. Fasting glucose levels were higher in patients with periodontal disease, and total bilirubin levels were lower. When divided by fasting glucose levels, high glucose level showed increase of periodontal disease with odds ratio of 1.031 (95% confidence interval 1.004-1.060). After adjusting for confounders, the results were significant with odds ratio of 1.032 (95% CI 1.004-1.061). CONCLUSIONS: Our study showed that KT patients, of whom uremic toxin clearance has been revolted, are yet at risk of periodontitis by other factors, such as high blood glucose levels.

Percutaneous radiofrequency ablation using internally cooled wet electrodes for treatment of colorectal liver metastases.

AIM: To evaluate the efficacy and safety of internally cooled wet (ICW) electrodes, which provide interstitial infusion of saline and intra-electrode cooling simultaneously, in the percutaneous radiofrequency ablation (RFA) of liver metastases from colorectal cancer. MATERIALS AND METHODS: From February 2008 to October 2010, 27 patients with 35 hepatic metastatic lesions (mean size 1.99cm; range 0.7-3.8cm) underwent RFA using ICW electrodes. Of these 35 tumours, 32 had diameters ≤3cm, and three had diameters of 3-4cm. Moreover, 18 tumours were non-subcapsular and 17 were subcapsular. RESULTS: No patients (0%) had major complications after RFA. During follow-up (median 27 months; range 4.5-36 months), 14 of the 35 treated lesions (40%) showed local tumour progression. The local tumour progression-free survival rates at 1 and 3 years were 73 and 56%, respectively. The local tumour progression-free survival period was significantly longer in patients with tumours ≤2cm than >2cm (p<0.001), but did not differ significantly between patients with non-subcapsular and subcapsular tumours (p=0.454). The overall 1 and 3 year survival rates after RFA were 100 and 77%, respectively. CONCLUSIONS: Percutaneous RFA using ICW electrodes is safe and technically feasible for the treatment of liver metastases from colorectal cancer. It provides effective local tumour control with low complication rates and reduced number of needle placements.

Immunoglobulin E-dependent active fatal anaphylaxis in mast cell-deficient mice.

Mast cells have long been believed to be the central effector cells in the development of immunoglobulin (Ig)E-dependent anaphylaxis. In this study, we investigated the role of mast cells in IgE-dependent hapten-induced active fatal anaphylaxis using mast cell-deficient WBB6F1- W/Wv (W/Wv) and congenic normal (+/+) mice. Although a 5-min delay in shock signs and death were observed in W/Wv mice, 100% fatal reactions to penicillin V (Pen V) occurred in both +/+ and W/Wv mice. Administration of monoclonal anti-IL-4 antibody completely prevented the fatal reactions, and the effect of anti-IL-4 was associated with its suppressive activity on Pen V-specific serum levels of IgE, but not IgG. The platelet-activating factor (PAF) antagonist, BN 50739, completely prevented the fatal reactions in both strains of mice. Our kinetic study revealed, in contrast to no elevation of plasma histamine level in W/Wv mice, high levels of PAF in the circulation after challenge in both +/+ and W/Wv mice, albeit to a lesser degree in the latter case. These data indicate that cells other than mast cells are sufficient to induce an IgE-dependent active fatal anaphylaxis by elaborating PAF, which is the critical mediator for fatal murine anaphylaxis.

Isolated perihepatic tuberculosis: imaging findings.

AIM: To review the imaging findings of isolated perihepatic tuberculosis without coexistent active tuberculosis elsewhere in the body. MATERIALS AND METHODS: Over a 9-year period, six patients with histopathologically proven perihepatic tuberculosis without simultaneous active tuberculosis elsewhere in the body were included in this study. Two radiologists retrospectively evaluated in consensus the location (right, left, or both perihepatic spaces), size (maximum diameter), morphology (ovoid or round), number, attenuation (low-, iso-, or high-attenuation compared with the adjacent liver parenchyma), and the presence or absence of contrast enhancement of the lesions on computed tomography (CT), and echogenicity (low-, iso-, or high-echogenicity compared with the adjacent liver parenchyma) of the lesions on ultrasonography. RESULTS: On CT, an isolated perihepatic lesion was located in the right perihepatic space in five patients, whereas three lesions were located in both perihepatic spaces in the remaining patient. The mean maximum diameter of the isolated perihepatic tuberculosis lesions was 29.7 mm. Isolated perihepatic tuberculosis appeared as an ovoid-shaped, homogeneous, and low-attenuating (n=5) or high-attenuating (n=1) lesion relative to the liver. There was peripheral rim enhancement of the lesion in two patients. On ultrasonography, isolated perihepatic tuberculosis was revealed as a homogeneous, low-echoic (n=5) or iso-echoic (n=1) lesion relative to the liver. CONCLUSION: Although various inflammatory or malignant lesions can be located in the perihepatic space, isolated perihepatic tuberculosis appears an ovoid-shaped, homogeneous, and low-attenuating or low-echoic lesion compared with the liver parenchyma on CT or ultrasonography.

Sequential delivery of BMP-2 and BMP-7 for bone regeneration using a heparinized collagen membrane.

To investigate the effect of the sequential delivery of bone morphogenetic proteins BMP-2 and BMP-7 on bone regeneration in rat calvarial defects (40 Sprague-Dawley rats, 8mm defect size), all animals were treated with a hydroxyapatite (HA)/tricalcium phosphate (TCP) bone graft covered with a collagen membrane. The experimental groups were as follows: (1) control group: unmodified collagen (no treatment); (2) BMP-2 group: 5 µg of BMP-2; (3) hep-BMP-7 group: 5 µg BMP-7 chemically bound to heparinized collagen; and (4) BMP-2/hep-BMP-7 group: 2.5 µg BMP-7 bound to heparinized collagen and subsequently treated with 2.5 µg BMP-2. Defect healing was examined at 2 and 8 weeks after surgery. The BMP-2 group showed the largest new bone area at week 2 (29.3 ± 7.3%; P = 0.009); new bone areas in the hep-BMP-7 and BMP-2/hep-BMP-7 groups were similar (11.8 ± 3.4% and 12.9 ± 5.71%, respectively; P = 0.917). After 8 weeks, the BMP-2/hep-BMP-7 group showed the largest new bone area (43.3 ± 6.2%), followed by the BMP-2 and hep-BMP-7 groups (P = 0.013). Accordingly, in comparison with single deliveries of BMP-2 and BMP-7, sequential delivery of BMP-2 and BMP-7 using a heparinized collagen membrane significantly induced new bone formation with a smaller quantity of BMP-2 in rat calvarial defects.

Electrodermal responsiveness, clinical variables, and brain imaging in male chronic schizophrenics.

We investigated the variables related to electrodermal nonresponsiveness in male chronic schizophrenics. In a comparison of 31 male chronic schizophrenics and 20 male normal controls, the schizophrenics showed a much higher incidence of nonresponders in phasic electrodermal responsiveness, and fewer spontaneous fluctuations (SFs) in tonic electrodermal activity. Among the schizophrenics, nonresponders showed fewer SFs and lower tonic skin conductance level (SCL). They also had more neuropsychological abnormalities of cognitive function and more severe symptoms (both positive and negative). Furthermore, patients with structural abnormality of the brain revealed by computerized tomographic measurements (increased ventricular brain ratio and maximum diameter of third ventricle) were overrepresented among electrodermal nonresponding schizophrenics. These findings suggest that electrodermal nonresponsiveness in chronic schizophrenic illness might be considered as a functional index associated with greater neuropsychological abnormalities and more severe symptoms.

Synthesis and thromboxane A2 antagonist activity of N-benzyltrimetoquinol analogues.

It is currently believed that the platelet thromboxane A2 (TXA2/PGH2) receptor is different from the vascular TXA2/PGH2 receptor. While the majority of TXA2 receptor antagonists are structurally related to the prostaglandins, trimetoquinol (TMQ) represents a unique nonprostanoid antagonist. TMQ also possesses beta-adrenergic activity; however, an N-benzyl substituent on TMQ has been shown to impart some selectivity for platelet antiaggregatory activity versus beta-adrenergic activity. In this study, we examined the synthesis and TXA2 antagonist activity of a series of substituted N-benzyl analogues of TMQ. While these analogues showed an apparent direct correlation between platelet antiaggregatory activity and electron-donating ability of the N-benzyl substituents, no such correlation could be demonstrated for the inhibition of contractile responses. Thus, nonprostanoid TXA2 antagonists can be used to demonstrate differences between platelet and vascular TXA2/PGH2 responses.

A biodegradable nanofiber scaffold by electrospinning and its potential for bone tissue engineering.

Microporous, non-woven poly( epsilon -caprolactone) (PCL) scaffolds were made by electrostatic fiber spinning. In this process, polymer fibers with diameters down to the nanometer range, or nanofibers, are formed by subjecting a fluid jet to a high electric field. Mesenchymal stem cells (MSCs) derived from the bone marrow of neonatal rats were cultured, expanded and seeded on electrospun PCL scaffolds. The cell-polymer constructs were cultured with osteogenic supplements under dynamic culture conditions for up to 4 weeks. The cell-polymer constructs maintained the size and shape of the original scaffolds. Scanning electron microscopy (SEM), histological and immunohistochemical examinations were performed. Penetration of cells and abundant extracellular matrix were observed in the cell-polymer constructs after 1 week. SEM showed that the surfaces of the cell-polymer constructs were covered with cell multilayers at 4 weeks. In addition, mineralization and type I collagen were observed at 4 weeks. This suggests that electrospun PCL is a potential candidate scaffold for bone tissue engineering.

Expression of glucose oxidase by using recombinant yeast.

The glucose oxidase gene (GO) of Aspergillus niger was cloned into the yeast shuttle vector YEp352 with combinations of various promoters and terminators, and then used to transform Saccharomyces cerevisiae. Expressed GO was successfully secreted into culture medium due to the presence of the intrinsic signal peptide of GO. Four different promoters fused to GO were tested: bidirectional galactose dehydrogenase 1 and 10 (GAL1, GAL10) promoters, glyceraldehyde-3-phosphate dehydrogenase (GPD) promoter and an yeast hybrid ADH2-GPD promoter consisting of alcohol dehydrogenase II (ADH2) and GPD promoter. The intrinsic terminator of GO as well as the GAL7 terminator were also compared for better production of GO. Deletion of most of the terminating region from GO yielded only a slight amount of GO while the presence of either terminator greatly increased GO production. The GAL10 promoter produced the least amount of GO, GAL1 and GPD promoters were moderate, and the ADH2-GPD hybrid promoter was the best among all tested. However, the hybrid promoter was tightly regulated by the presence of an excess amount of either glucose or ethanol, and it appeared that 2% glucose and 1. 5% ethanol supplement was the best concentration for GO production. It was possible to produce 260 IU ml(-1) of GO, an equivalent of 5 g l(-1), under the presence of 2% glucose and 1.5% ethanol. UV mutagenesis of a recombinant S. cerevisiae was also applied and it further increased the yield of GO to 460 IU ml(-1) under the presence of 2% glucose and 1.5% ethanol without any changes in cell growth. Corn steep liquor which is commonly used in bioindustry is a good alternative substrate for high priced glucose for the hybrid promoter and suggests a cost effective means for commercial mass production of GO using recombinant yeast.

Acute respiratory distress syndrome caused by miliary tuberculosis: a multicentre survey in South Korea.

BACKGROUND: Miliary tuberculosis (TB) is an unusual cause of acute respiratory distress syndrome (ARDS). OBJECTIVE: To evaluate the clinical characteristics and outcomes of patients with ARDS caused by miliary TB admitted to the intensive care unit (ICU). DESIGN: A total of 67 patients were enrolled during the period 1999-2008. RESULTS: The median age of the patients was 56 years (range 17-81), 19 (28.4%) were aged >71 years, and 38 (56.7%) were male. All-cause mortality in the ICU and hospital were respectively 58.2% and 61.2%. Of the total number of enrolled patients, 49 (73.1%) were prescribed anti-tuberculosis medication within 3 days of hospital admission. On the day of ARDS diagnosis (10.0 ± 3.7 vs. 7.4 ± 3.5, P = 0.005), non-survivors had a significantly higher Sequential Organ Failure Assessment (SOFA) score than survivors. Multivariate analysis showed that SOFA score on the day of ARDS diagnosis was a significant predictor of survival (OR 0.809, 95%CI 0.691-0.946, P = 0.008). It was difficult to determine the efficacy of systemic corticosteroids on patient survival. CONCLUSION: ARDS caused by miliary TB was associated with a high in-hospital mortality rate, with SOFA score on the day of ARDS diagnosis being a valuable prognostic indicator.

Effect of splenic artery embolization for splenic artery steal syndrome in liver transplant recipients: estimation at computed tomography based on changes in caliber of related arteries.

PURPOSE: To estimate the effect of splenic artery embolization (SAE) on blood flow in orthotopic liver transplantation (OLT) recipients with splenic artery steal syndrome (SASS) based on changes in caliber of related arteries upon serial computed tomography (CT) scans. METHODS: Between 2004 and 2007, nine OLT recipients with SASS underwent SAE. They had CT scans before and after SAE: short-, mid-, and long-term, ie, approximately 1 week, 1 month, and 1 year, respectively. The diameters of the celiac axis (CA), common hepatic artery (CHA), and splenic artery (SA) were measured with arterial phase of each CT scan and the ratios of SA to CHA diameter (SA/CHA) calculated to analyze their changes during the follow-up period. RESULTS: The diameters of celiac axis, CHA, and SA and SA/CHA changed most rapidly during the short-term period. The CHA diameter significantly increased short-term post-SAE by CT and slightly decreased thereafter. However, the mid-term and long-term post-SAE CT values were still significantly greater than those on the pre-SAE CT. The SA diameter steadily decreased throughout the follow-up. The SA/CHA decreased until the mid-term. The SA diameter and SA/CHA were significantly smaller upon mid-term and long-term post-SAE CT compared with those at pre-SAE CT. CONCLUSIONS: The effect of SAE to improve hepatic arterial flow in OLT recipients with SASS might be expected for at least approximately one year. The effect maximally occurred during the short-term after SAE on the basis of changes in the caliber of related arteries upon CT.

Development of a Decision Support Model for Screening Attention-deficit Hyperactivity Disorder with Actigraph-based Measurements of Classroom Activity.

OBJECTIVE: Questionnaire-based ADHD screening tests may not always be objective or accurate, owing to both subjectivity and prejudice. Despite attempts to develop objective measures to characterize ADHD, no widely applicable index currently exists. The principal aim of this study was to develop a decision support model for ADHD screening by monitoring children's school activities using a 3-axial actigraph. METHODS: Actigraphs were placed on the non-dominant wrists of 153 children for 3 hours, while they were at school. Children who scored high on the questionnaires were clinically examined by child psychiatrists, who then confirmed ADHD. Mean, variance, and ratios of low-level (0.5-1.0G) and high-level (1.6-3.2G) activity were extracted as activity features from 142 children (10 ADHD, 132 non-ADHD). Two decision-tree models were constructed using the C5.0 algorithm: [A] from whole hours (class + playtime) and [B] during classes. Accuracy, sensitivity, and specificity were evaluated. PPV, NPV, likelihood ratio, and AUC were also calculated for evaluation. RESULTS: [Model A] One child without ADHD was misclassified, resulting in an accuracy score of 99.30%. Sensitivity and NPV were 1.0000. Specificity and PPV were 0.992 and 0.803-0.909, respectively. [Model B] Two children without ADHD were misclassified, resulting in an accuracy score of 98.59%. Specificity and PPV were scored at 0.985 and 0.671-0.832, respectively. CONCLUSION: The selected features were consistent with the findings of previous studies. Objective screening of latent patients with ADHD can be accomplished with a simple watch-like sensor, which is worn for just a few hours while the child attends school. The model proposed herein can be applied to a great many children without heavy cost in time and manpower cost, and would generate valuable results from a public health perspective.

Increase of modified retrograde to antegrade flow ratio on doppler ultrasounds of the hepatic vein indicating tricuspid regurgitation during follow-up of liver transplantation: correlation with echocardiographic results.

The purpose of this study was to explore the best parameter of hepatic vein (HV) Doppler ultrasounds (DUS) that correlated with echocardiographic findings of and particularly the optimal cutoff value for tricuspid regurgitation (TR) following liver transplantation (LT). Thirty-six patients underwent echocardiography and DUS after LT from January 2006 to July 2007. Echocardiographic records were searched for TR grade and peak velocity of TR flow. The HV DUS parameters included peak velocity of retrograde flow (R), peak velocity of antegrade flow (A), the difference between R and A (R-A), the ratio of R to A (R/A ratio), and a modified R/A ratio, namely, the product of the R/A ratio and the R/A duration ratio. Correlation tests and receiver-operator characteristic analyses explored their interrelations and to obtained cutoff values to diagnose moderate and severe TR. TR grade best correlated with the modified R/A ratio (rho = 0.585), followed by the R/A ratio (rho = 0.503) and R (rho = 0.455). The modified R/A ratio was the most accurate parameter for the diagnosis of moderate and severe TR (Az = 0.825 and 0.895, respectively); its cutoff value was > or =0.11 for moderate TR (sensitivity and specificity both 77.78%) and 0.13 for severe TR (sensitivity, 100%; specificity, 81.2%). The modified R/A ratio best correlated with echocardiographic results of TR, although the strength of correlation was only moderate. Additionally, the modified R/A ratio was an accurate DUS parameter to diagnose moderate and severe TR among patients following LT.

Gastric schwannomas: radiological features with endoscopic and pathological correlation.

AIM: To describe the radiological, endoscopic, and pathological findings of gastric schwannomas in 16 patients. MATERIALS AND METHODS: The radiological, endoscopic, and pathological findings of 16 surgically proven cases of gastric schwannoma were retrospectively reviewed. All patients underwent computed tomography (CT) and four patients were evaluated with upper gastrointestinal series. Two radiologists reviewed the CT and upper gastrointestinal series images by consensus with regard to tumour size, contour, margin, and growth pattern, the presence or absence of ulcer, cystic change, and the CT enhancement pattern. Endoscopy was performed in eight of these 16 patients. Six patients underwent endoscopic ultrasonography. Pathological specimens were obtained from and reviewed in all 16 patients. Immunohistochemistry was performed for c-kit, CD34, smooth muscle actin, and S-100 protein. RESULTS: On radiographic examination, gastric schwannomas appeared as submucosal tumours with the CT features of well-demarcated, homogeneous, and uncommonly ulcerated masses. Endoscopy with endoscopic ultrasonography demonstrated homogeneous, submucosal masses contiguous with the muscularis propria in all six examined cases. On pathological examination, gastric schwannomas appeared as well-circumscribed and homogeneous tumours in the muscularis propria and consisted microscopically of interlacing bundles of spindle cells. Strong positivity for S-100 protein was demonstrated in all 16 cases on immunohistochemistry. CONCLUSION: Gastric schwannomas appear as submucosal tumours of the stomach and have well-demarcated and homogeneous features on CT, endoscopic ultrasonography, and gross pathology. Immunohistochemistry consistently reveals positivity for S-100 protein in the tumours.

Abdominal cavernous Iymphangiomas: CT findings.

Two adult patients with histopathologically proved cavernous lymphangiomas and one adult patient with lymphangiomas of strongly presumed cavernous type by cytologic and computed tomographic findings are reported. On computed tomograms, multiple, aggregated, small, and tiny cysts without a solid portion, along the lymphatic channels are characteristic computed tomographic findings for cavernous lymphangiomas.

Slow transit constipation in children.

Patients with chronic constipation that fails to respond to treatment remain a challenge for paediatricians and surgeons. Ongoing work in our institution suggests that a number of children with intractable symptoms have slow transit constipation, which has only been described recently in paediatrics. Common features of slow transit are: delayed passage of the first meconium stool beyond 24 h of age, symptoms of severe constipation within a year, or treatment-resistant 'encopresis' at 2-3 years, soft stools despite infrequent bowel actions, and delay in colonic transit on a transit study. A proportion of children with slow transit constipation have an abnormality of intestinal innervation associated with the dysfunctional colonic motility, recognized as intestinal neuronal dysplasia (IND). Intestinal neuronal dysplasia type B, the most common variant of IND, is defined on rectal biopsy by hyperplasia of the submucosal plexus. On laparoscopic colon muscle biopsy, many specimens show reduced numbers of excitatory substance P-immunoreactive nerve fibres in the circular muscle. Functional markers of the nerves allow new diagnostic criteria to be developed which may also allow a more rational approach to treatment. The aetiology remains obscure and the optimal management poorly defined, although subtotal colectomy, proximal colostomy or appendicostomy (for antegrade enemas) have been tried. Once the anatomy and physiology of the colon in children with slow colonic transit is better understood, we will have defined not only a new form of constipation, but also will be able to consider new therapies.