Ethanol lock therapy in pediatric patients: A multicenter prospective study.

BACKGROUND: Ethanol lock therapy (ELT) has been performed for the purpose of preserving central venous catheters (CVC) in central venous catheter-related blood stream infection (CRBSI), but evidence for its effectiveness is not established. We conducted a multicenter, prospective study on the ELT protocol to ascertain its safety and effectiveness against CRBSI. METHODS: The subjects were patients aged over 1 year with potential for developing CRBSI who had long-term indwelling silicone CVCs. After culturing the catheterized blood, a 70% ethanol lock was performed daily for 2-4 h for 7 days. The effectiveness rate of ELT for single and multiple courses, the presence or absence of relapse of CRBSI within 4 weeks of treatment, and whether the CVC could be salvaged after 4 weeks were examined. RESULTS: From September 2014 to August 2018, 49 cases from six hospitals were enrolled in the study. Catheter blockage was seen in one case and the CVC was removed. A single course of ELT was effective in episodes 88% (42/48). In the remaining three episodes that failed after a single course of ELT, a second ELT was performed; however, all were ineffective. In episodes 93% (40/42), no CRBSI relapse was seen up to 4 weeks after the end of treatment. In episodes 84% (41/49), the catheter could be preserved for 4 weeks or more after the end of treatment. Facial flushing was seen in two cases as an adverse event; however, this was transient and soon disappeared. CONCLUSION: ELT is effective for 88% of CRBSI and 84% of catheters can be salvaged; therefore, this protocol is considered useful. TRIAL REGISTRATION: UMIN000013677.

Elevated expression of transforming growth factor ß3 in carbon tetrachloride-treated rat liver and involvement of retinoid signaling.

Transforming growth factor (TGF) ß is a pro-fibrotic cytokine. While three isoforms (TGF-ß1, 2 and 3) are known, the functional differences between them are obscure. To investigate the roles of TGF-ß isoforms during liver fibrogenesis, male Wistar rats were administrated carbon tetrachloride (CCl4) subcutaneously twice a week for two months. Livers were excised and sectioned for histochemical examinations. These livers were also used to quantitate the expression of genes associated with fibrogenesis, including TGF-ß isoforms, as well as those associated with retinoid metabolism. Expression levels of Tgfb1 and Tgfb3 were up-regulated in CCl4-treated rat livers while that of Tgfb2 was not changed. The mRNAs for lecithin-retinol acyltransferase (Lrat) and retinoic acid hydroxylase, Cyp26a1, were also elevated. By immunohistochemical staining, TGF-ß3 protein was found to be localized mainly in liver parenchymal cells (hepatocytes). These results indicate that retinoid mobilization likely takes place within the rat's liver following CCl4 treatment, and suggest the possibility that the expression of Tgfb mRNA is regulated by retinoic acid receptors. Reporter analyses of a region of the Tgfb3 gene were performed using the rat liver parenchymal cell line, RLC-16, and a positively responsive region was identified within its intron.

Transhiatal jejunal interposition preserving the whole stomach and vagal trunk for a benign esophageal stricture in a male adolescent: report of a case.

Benign esophageal strictures are generally treated with medication and balloon dilation; however, when repeated dilations fail, surgery is the only option. When performing surgery for benign esophageal stricture in young patients, it is important to consider not only the surgical stress and likelihood of complications but also digestive function after reconstruction, the durability of the reconstruction, and the potential for cancerous change in the reconstructed organs. We describe how we treated a 14-year-old boy with benign esophageal stricture by performing transhiatal esophagectomy assisted by mediastinoscopy, preserving the whole stomach and vagus nerve, and interposing pedicled jejunum between the cervical esophagus and stomach through a posterior mediastinal route, with good long-term results.

Antiproliferative and proapoptotic effects of tocopherol and tocol on activated hepatic stellate cells.

Activated hepatic stellate cells (HSCs) play crucial roles in liver fibrosis. In the course of liver injury, HSCs, which reside in perisinusoidal spaces and lose lipid droplets, morphologically change into a myofibroblastic phenotype and acquire an increased proliferation activity in what is known as the activated state. We have investigated therapeutic strategies for liver fibrosis by promoting spontaneous reversion or inducing apoptosis in activated HSCs. Vitamin E consists of four tocopherols and four tocotrienols, all of which are well-known antioxidants. In this study, the antiproliferative and proapoptotic effects of a tocol, which lacks methyl groups attached to the chromanol ring, and four tocopherols were investigated using activated HSCs. δ-Tocopherol and tocol exhibited relatively high proliferation inhibitory and proapoptotic abilities. However, they did not show proliferation inhibition ability on primary hepatocytes or HepG2 cells. Significant cell detachment was also observed in δ-tocopherol- and tocol-treated HSCs. Decreased protein expressions of α-smooth muscle actin and ß1 integrin were observed in a dose-dependent manner. These results indicate that δ-tocopherol and tocol induce anoikis in activated HSCs.

Onset of apoptosis in the cystic duct during metamorphosis of a Japanese lamprey, Lethenteron reissneri.

A nonparasitic lamprey in Japan, Lethenteron reissneri, stops feeding prior to the commencement of metamorphosis. Resumption of feeding cannot take place due to major alterations in the digestive system, including loss of the gall bladder (GB) and biliary tree in the liver. This degeneration of bile ducts is considered to depend on programmed cell death or apoptosis, but molecular evidence of apoptosis remains lacking. Using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining and immunohistochemistry with an antibody against active caspase-3, we showed that epithelial cells of the cystic duct (CD) and GB became TUNEL-positive by the early metamorphosing stage. Immunohistochemical staining of active caspase-3, a key mediator in the apoptotic cascade, showed that the apoptotic signal was initiated in the region around the CD in the late larval phase. In later stages, active caspase-3-positive epithelial cells were also observed in the large intrahepatic bile duct (IHBD) and peripheral small IHBDs. At the early metamorphosing stage, bile canaliculi between hepatocytes were dilated and displayed features resembling canaliculi in cholestasis. Onset of apoptosis around the CD, which is the pathway for the storage of bile juice, and progression of apoptosis towards the large IHBD, which is the pathway for the secretion of bile juice, may lead to temporary intrahepatic cholestasis. The present study represents the first precise spatial and temporal analysis of apoptosis in epithelial cells of the biliary tract system during metamorphosis of any lamprey species.

Anal ultraslow waves and high anal pressure in childhood: a clinical condition mimicking Hirschsprung disease.

PURPOSE: Anal ultraslow waves (USWs) have been described in several clinical conditions closely related to chronic constipation associated with high anal pressure; however, USW-related clinical manifestations in childhood are poorly understood. The purpose of this study is to elucidate the clinical relevance of USWs in childhood. METHODS: Manometric recordings of 118 cases including 70 children with constipation and 16 patients with Hirschsprung disease were analyzed. RESULTS: Ultraslow waves were seen in 4 of 70 children with constipation. None of the controls or patients with Hirschsprung disease exhibited USWs. The 4 patients comprised 2 infants with marked abdominal distension mimicking Hirschsprung disease and 2 children (aged 4 and 8 years) with intractable constipation accompanying hemorrhoid or anal fissure. The manometric findings of the USW-positive patients showed a markedly high anal resting pressure and high frequency of slow waves compared to controls, patients with constipation not accompanied by USWs or patients with Hirschsprung disease. CONCLUSION: Children with USWs exhibit symptoms mimicking Hirschsprung disease in infants and chronic intractable constipation in older children. In manometric studies of children, more attention should be paid not only to rectoanal reflex, but also USWs.

Multiple clinical presentations of anal ultra slow waves and high anal pressure: megacolon, hemorrhoids and constipation.

The physiopathology of idiopathic chronic constipation is complex and yet to be investigated. In the manometric studies of the patients with severe chronic constipation, we noticed that some patients with megacolon show very slow periodical (< 2/min) pressure change in the anal canal, namely ultra slow waves (USWs). USWs are considered to represent the hyperactivity of the internal anal sphincter; however, USW-related clinical presentations have yet to be investigated. We retrospectively re-evaluated the patient records and manometric studies of 85 cases, 51 subjects without defecatory problems and 34 patients with constipation, to elucidate USW-related clinical presentations. USWs were seen in 10 patients, including eight patients with chronic constipation and two subjects without defecatory problems. Out of the eight patients with constipation, one had no organic change in the anorectum, three had hemorrhoids and four exhibited megacolon. Manometric and pathological studies proved that none of the four patients with megacolon was suffering from Hirschsprung's disease. Among the 51 subjects without defecatory problems, only two had USWs. Anal pressure in the USW-positive group (106.0 +/- 37.0 cmH2O) was significantly higher than that in the group without defecatory problems (56.0 +/- 27.0 cmH2O) or constipated patients without USWs (55.0 +/- 26.0 cmH2O). Megacolon and high anal pressure, as well as chronic constipation and hemorrhoids, were the clinical presentations related to USWs. This is the first report to show the clinical relevance of USWs to megacolon. USWs should be recognized as an important manometric finding indicating a possible new clinical entity in chronic constipation.

Evaluation of anorectal function in patients with tethered cord syndrome: saline enema test and fecoflowmetry.

OBJECT: Disturbance in anorectal function is a major factor restricting the activities of daily living in patients with spinal cord disorders. To detect changes in anorectal motilities due to a tethered spinal cord, anorectal functions were evaluated using a saline enema test and fecoflowmetry before and after patients underwent untethering surgery. METHODS: The bowel functions in five patients with a tethered cord syndrome (TCS) were evaluated by performing a saline enema test and fecoflowmetry. The contractile activity of the rectum, the volume of infused saline tolerated in the rectum, anal canal pressure, and the ability to evacuate rectal content were examined. The characteristic findings in anorectal motility studies conducted in patients with TCS were a hyperactive rectum, diminished rectal saline-retention ability, and diminished maximal flow in saline evacuation. A hyperactive rectum was considered to be a major contributing factor to fecal incontinence. In one asymptomatic patient diminished anal squeezing pressure was exhibited and was incontinent to liquid preoperatively, but recovered after surgery. Two patients who underwent surgery for myeloschisis as infants complained of progressive fecal incontinence when they became adolescents. In one patient fecal incontinence improved but in another patient no improvement was observed after untethering surgery. CONCLUSIONS: Fecodynamic studies allow the detection of neurogenic disturbances of the anorectum in symptomatic and also in asymptomatic patients with TCS. More attention should be paid to the anorectal functions of patients with TCS.

Fecoflowmetric evaluation of anorectal function and ability to defecate in children with idiopathic chronic constipation.

Idiopathic chronic constipation (ICC) is one of the most common clinical conditions in children. The pathophysiology is multifactorial and differs from case to case. To investigate the relationship between anorectal motility (ARM) and clinical course in children with ICC, anorectal function was evaluated using fecoflowmetry in nine children aged 2-14 years (mean 6.1). Three were boys and six were girls. Pressure fluctuations in the rectum and anal canal were simultaneously recorded during saline (250-500 ml) infusion into the rectum. The dynamics of defecation were evaluated using recordings of the saline evacuation curve from the rectum in each patient. Seven patients showed periodic contractions of the rectum accompanied (five) or unaccompanied (two) by relaxations of the anal canal during saline infusion. These patients achieved comfortable spontaneous defecation during follow-up periods ranging from 5 to 20 months. The other two exhibited no rectal contractions in spite of relaxations of the anal canal, and did not respond well to long-term medical management. In eight patients segmental fecoflowmetric curves showed a significantly lower flow rate and longer evacuation time than those of controls. Fecoflowmetry is a simple and non-invasive technique for evaluation of the ability to defecate. Disturbances of ARM may play an important role in patients with severe ICC. When evaluating anorectal function in children with chronic constipation, more attention should be paid to ARM and fecodynamics.

Renal focal tubulointerstitial fibrosis with short bowel syndrome: report of a case.

We report a male patient with short bowel syndrome (SBS) and renal focal tubulointerstitial fibrosis (FTIF). Seven years after surgery, he was introduced to us due to severe undernutrition, an impairment of growth hormone (GH) secretion, and abnormally low levels of plasma citrulline and arginine at 11 years 7 months of age, just before nutritional support using total parenteral nutrition (TPN) was begun. Thereafter, the support was changed to home TPN with GH supplementation. After an improvement of the disorders, GH was stopped at 17 years 3 months of age. However, hyperuricemia appeared and a renal biopsy revealed FTIF at 20 years of age. Home TPN was continued twice a week because the plasma arginine level was still low. His follow-up biopsy at 23 years of age showed morphometric amelioration. Arginine deficiency following SBS may be associated with FTIF. The cause of hyperuricemia after SBS therefore needs to be investigated in detail.

Evaluation of anorectal functions of children with anorectal malformations using fecoflowmetry.

BACKGROUND/PURPOSE: A simple and objective method evaluating the bowel functions of patients with anorectal anomalies is necessary. The authors applied fecoflowmetry and saline enama test for patients with anorectal anomalies to evaluate the fecodynamics and anorectal motilities in these children. METHODS: The bowel functions of 16 patients who underwent repair for anorectal malformations and 5 normal controls were evaluated by saline enema test and fecoflowmetry. The correlations between the clinical scores for the bowel functions and the parameters in fecodynamic studies were investigated. RESULTS: Seven of 16 patients exhibited periodical contractions of the rectum synchronized with relaxations of the anal canal during saline infusion as did the controls and had significantly higher clinical scores than the other patients. Two patients with severe chronic constipation lacked rectal contractions. Among the fecoflowmetric parameters, the maximum flow, average flow, and tolerable volume of saline infused into the rectum were significantly lower in the patients with low clinical scores than those of the controls. The maximal squeeze pressure and resting anal pressure were not significantly different between the patients and controls. CONCLUSION: Fecodynamic studies, such as fecoflowmetry and saline enema test, help in obtaining clinical indicators for the bowel functions of patients with anorectal anomalies.