The herbal medicines Inchinkoto and Saireito improved hepatic fibrosis via aquaporin 9 in the liver of a rat bile duct ligation model.

OBJECTIVE: To determine if the administration of the Japanese herbal medicines Inchinkoto (ICKT) and Saireito (SRT) ameliorate hepatic fibrosis and derangement of hepatocyte aquaporins (AQPs) following bile duct ligation (BDL) in a rat model of obstructive cholestasis. MATERIALS AND METHODS: Five groups of Wistar rats were used, and the groups included sham surgery (Sham group), BDL with no treatment (NT group), BDL plus ICKT (ICKT group), BDL plus SRT (SRT group), and BDL plus ICKT and SRT (SRT/ICKT group). Each herbal medicine was administered at 1 g/kg/day on the first postoperative day. The serum levels and various clinical markers were measured with real-time polymerase chain reaction. Staining was used to evaluate the degree of fibrosis and the inflammatory responses. RESULTS: Serum aspartate aminotransferase and alanine aminotransferase in the ICKT and SRT/ICKT groups were significantly lower than those in the NT group. NF-κB mRNA expression was significantly decreased in the ICKT group and the SRT/ICKT group compared with the NT group. AQP9 mRNA expression was significantly increased in the ICKT group and the SRT/ICKT group compared with the NT group. The degree of Masson's trichrome staining in the SRT/ICKT group was significantly lower than that in the NT group. The degree of NF-κB staining in the SRT/ICKT group was significantly lower than that in the NT, ICKT, or SRT group. CONCLUSIONS: The postoperative administration of ICKT and SRT induced synergistic beneficial effects, resulting in the reduction of hepatic fibrosis via mechanisms involving the inhibition of NF-κB expression and the improvement of AQP9 downregulation.

The management and outcome of pediatric blunt chest-abdominal injuries.

BACKGROUND: The aim of this study was to determine the frequency and nature of pediatric blunt chest-abdominal injuries (BCAIs) and to summarize their management, ranging from non-operative management (NOM), with or without angioembolization (AE), to surgical treatment. METHODS: This retrospective study included patients admitted to our hospital for BCAIs from January 1996 to December 2017. The age, injury pattern, organs of injury, outcome, and treatment were summarized. RESULTS: One hundred and thirty-two patients (98 males, 34 females, mean age 7.68 years ± 3.58, range 1-15 years) were included in the study. Their injuries resulted from motor-vehicle traffic incidents (n = 60), single-bicycle injuries (n = 16), falls (n = 33), sports (n = 10), assault (n = 6), abuse (n = 3), and others (n = 4). There were no injured organs in 31 cases, while there were 130 injured organs in 101 cases, including the liver (n = 42), spleen (n = 35), lung (n = 23), kidney (n = 13), intestine (n = 10), pancreas (n = 5), and adrenal gland (n = 2). Angiography (AG) was performed in 20 cases, and NOM with AE was performed in 16 cases, including 17 organs (liver injury [n = 9], splenic injury [n = 5], and kidney injury [n = 4]). Surgical treatment was performed in eight cases (splenic injury in one, pancreas injury in one, and intestinal injury in six). NOM without AE was performed in the other cases. CONCLUSIONS: The management of organ injury must take into consideration the management of integrated bleeding. It is recommended that children with severe organ injury are treated in dedicated trauma centers in which AE is available.

Analyses of the relationship between a 'number of reflux episodes' exceeding 70 and the pH index in neurologically impaired children by evaluating esophageal combined pH-multichannel intraluminal impedance measurements.

BACKGROUND: The present study aimed to evaluate the characteristics associated with a number of reflux episodes (NoRE) of 70 by comparing the clinical and multichannel intraluminal impedance pH measurements (pH/MII) and pH index (pHI) in neurologically impaired (NI) children. PATIENTS AND METHODS: NI children (1-16 years of age) in whom pH/MII had been measured for GERD study were enrolled in this study. All children were divided into NoRE >70 or ≤70 and pHI >4.0 or ≤4.0, >5.0 or ≤5.0 or >7.0 or ≤7.0. In addition, the NI children with pHI >4.0, >5.0 and >7.0 were subdivided into NoRE >70 and ≤70 groups. The clinical and pH/MII measurements were compared between each of the two groups. The cutoff values of pHI and baseline impedance (BI) (Z6) were calculated to discriminate NoRE >70 and ≤70. RESULTS: A total of 61 NI children were enrolled in this study. There was a significant difference in the acid-related parameters, the NoRE (nonacid) and BI between NoRE >70 and ≤70, acid-related parameters and BI between pHI >4.0 and ≤4.0, >5.0 and ≤5.0 and >7.0 and ≤7.0 groups. Furthermore, a significant difference was still observed in the BI between NoRE >70 and ≤70 groups among patients with pHI >4.0, >5.0 or >7.0. The cutoff values of pHI and BI (Z6) for discriminating NoRE >70 and ≤70 were 9.2 and 1049Ω, respectively. CONCLUSION: The present study indicates that NoRE 70 corresponds to GERD in which patients suffer severe acid exposure with pH of around 9% and esophageal mucosal damage with low BI value in NI children.

Clinical Efficacy of Herbal Medicine for Pediatric Lymphatic Malformations: A Pilot Study.

BACKGROUND: Lymphatic malformations (LMs) are congenital malformations of the lymphatic system that commonly affect the head and neck region and cause marked cosmetic and functional complications. In this pilot study, we present eight children with LMs treated using an herbal medicine for this indication. METHODS: Between January 2009 and May 2014, eight children (four boys, four girls) with LMs were treated using oral administration of an herbal medicine, Eppikajyutsuto (TJ-28; Tsumura, Tokyo, Japan), as monotherapy. RESULTS: Four of the cases were macrocystic and four were mixed micro- and macrocystic. The mean treatment duration was 7.2 ± 2.9 months (range 5-12 mos). The mean LM volume shrinkage on magnetic resonance imaging was 54.5 ± 38.3% (macrocystic 73.6 ± 27.0%; mixed micro- and macrocystic 35.4 ± 41.5%). One of four macrocystic lesions had a marked reduction, two had a moderate reduction, and one had no response. A marked reduction was observed in three of the four mixed micro- and macrocystic cases; the other mixed cystic case had no response. The treatment was well tolerated, without severe adverse events. CONCLUSIONS: This preliminary study demonstrates the beneficial effects of TJ-28. Further evaluations of this therapeutic modality are warranted.

Pre and post-operative evaluation of gastroesophageal reflux and esophageal motility in neurologically impaired children using combined pH-multichannel intraluminal impedance measurements.

BACKGROUND: Gastroesophageal reflux disease (GERD) in patients with neurological impairment (NI) has not been fully studied before and after fundoplication procedure because their characteristics such as generalized gastrointestinal dysmotility, non-acid reflux, and the proximal reflux due to feeding of enteral nutrition via a nasogastric tube prevent their GERD from being detected by 24 h pH monitoring. The aim of this study was to elucidate whether multichannel impedance-pH measurement (pH/MII) is able to detect the subtypes of GERD and the differences in the reflux episodes of the severity of GERD, the ingestion pathway, and before and after fundoplication. The second aim was to determine whether a trial evaluation of dry swallows was able to be used to assess the esophageal motility of NI patients as an alternative examination. PATIENTS AND METHODS: The 24 h pH/MII was conducted on 20 NI children [15 were the patients before Nissen's fundoplication (BN), of whom, six were fed orally (FO) and nine were fed via nasogastric tube (NGT), and five were the patients after Nissen's fundoplication (AN)]. All reflux episodes were evaluated and compared between patients with pathological GERD (PG) and non-pathological GERD (NG) and between patients who had FO and NGT and patients between BN and AN. Dry swallows were conducted to evaluate the esophageal motility. The average bolus presence time (BPT) and total bolus transit time (TBTT) were compared between the PG and NG, FO and NGT, and the BN and AN subgroups. RESULTS: A total of 1,064 reflux episodes were detected by pH/MII. Of those, 303 (28.5 %) were non-acid-related and 477 episodes reached the proximal esophagus. Of the 12 patients (57.1 %) showing pathological GERD, two cases (16.7 %) demonstrated predominantly weakly acidic PG. More than half of the reflux episodes of PG patients reached to the proximal esophagus. The numbers of total reflux and proximal reflux episodes in the PG were significantly higher than those in NG patients. The number of proximal reflux episodes in the FO group was significantly higher than that in the NGT groups, whereas NGT patients showed more non-acidic reflux episodes than FO patients. A trial evaluation of dry swallows demonstrated no significant differences in this study. CONCLUSION: The pH/MII was useful to detect the subtype of GERD in NI patients which could not be detected by 24 h pH monitoring. It can, therefore, be considered to have first priority for testing NI patients who are suspected to be suffering from GERD.

Infantile neuroblastoma of the urinary bladder detected by hematuria.

Malignant tumors of the urinary bladder in infants are extremely rare. Rhabdomyosarcoma is the most likely tumor in this site, whereas neuroblastoma of the urinary bladder is exceedingly uncommon and is not listed as a differential diagnosis for tumors of this site. We present a case of neuroblastoma arising from the dome of the bladder wall, detected by hematuria. Only six cases of neuroblastoma originating from the bladder, including the present case have been reported. Of the cases, five arose from the dome of the bladder wall. In this report, the differential diagnosis of bladder tumors in children is discussed. A diagnosis of neuroblastoma should be taken into consideration, especially in the case of tumors arising from the dome of the bladder wall despite an uncommon location.

[Kampo medicine in the pediatric surgical field].

Kampo medicine has been used for over 4,000 years. Recently, some Kampo formulas have been prescribed for postoperative pediatric patients with gastrointestinal anomalies and disease. However, it has been only 30 years since Kampo medicine has been widely used in the pediatric surgical field. Some of the principal Kampo formulas used for daily treatment in the pediatric surgical field are: Rikkunshito and Bukuryouin-Gou-Hangekoubokuto for patients after upper gastrointestinal surgery; Daikenchuto for patients after colorectal surgery; Inchinkoto for postoperative patients with biliary atresia; and Hainosankyuto for periproctal abscess. Kampo formulas according to the postoperative condition are reviewed from the viewpoint of evidence-based medicine, our experience, and experiments. The results of the Kampo treatments listed above were superior to the results when a Kampo formula was not administered in pediatric patients postoperatively.

Difficulty in the Diagnosis of Biliary Atresia Splenic Malformation Syndrome In Utero.

The fetus of a 30-year-old pregnant Japanese woman was diagnosed with absence of inferior vena cava (IVC) and azygos continuation of interrupted IVC without cardiac anomalies at 34 weeks of gestation, and a healthy male neonate weighing 2,910 g was delivered at 37 weeks of gestation. On day 42 after birth, direct bilirubin predominant hyperbilirubinemia and high serum gamma-GTP levels were detected. Computed tomography revealed the presence of a lobulated and accessory spleen, and laparotomy demonstrated type III biliary atresia (BA), confirming the final diagnosis of BA splenic malformation (BASM) syndrome. In retrospect, non-visualization of the gallbladder was missed in utero. The combination of the absence of IVC and BA without cardiac anomalies is far less likely to occur in left isomerism. Although BA remains difficult to detect in utero, special attention should be paid to cases of BA associated with findings of left isomerism, including the absence of IVC, to enable early diagnosis and treatment of BASM.

The herbal medicine Inchinko-to reduces hepatic fibrosis in cholestatic rats.

PURPOSE: Several studies have reported the herbal medicine Inchinko-to (ICKT) to have an antifibrotic effect which thus leads to an improvement of hepatic injury. However, there are still few reports of its use in the treatment of cholestatic liver disorder. The aim of this study was to clarify whether the administration of ICKT will ameliorate hepatic fibrosis and injury in cholestatic rats. MATERIALS AND METHODS: We performed bile duct ligation on 7-week-old male cholestatic Wistar rats and assigned them to one of three groups according to the method of treatment: (1) the SHAM group, (2) the NT-group (non-treatment group), and (3) the T-group (treatment-group). Rats in the T-group were orally administered ICKT (TJ-135) at a dose of 1 g/kg/day and were killed on the 17th postoperative day. We subsequently investigated the levels of fibrosis and various clinical markers through measurement of the following: serum levels of AST and ALT; tissue transforming growth factor-beta 1 (TGF-beta1); tissue inhibitor metalloprotease-1 mRNA (TIMP-1 mRNA) through real-time PCR analysis; and Azan staining and immunohistochemical staining of alfa-smooth muscle actin (alfa-SMA) to evaluate the degree of fibrosis. RESULTS: The levels of serum AST, serum ALT, and TGF-bata1 in the T-Group were significantly lower than those in the NT-Group. In addition, staining of Azan and alfa-SMA in the T-Group was significantly lower than those in the NT-Group. CONCLUSION: ICKT may help reduce hepatic fibrosis and injury by controlling stellate cell activation.

Infantile juvenile xanthogranuloma of the chest wall mimicking mesenchymal hamartoma: report of a case.

Juvenile xanthogranuloma (JXG) is essentially a benign neoplasm arising from any site on the body; however, there has so far been only one report of JXG located on the chest wall involving a rib. This report presents a rare case finally diagnosed as JXG based on histopathological and immunohistochemical examinations.

Thoracic lymphangiomatosis with massive chylothorax after a tumor biopsy and with disseminated intravenous coagulation--lymphoscintigraphy, an alternative minimally invasive imaging technique: report of a case.

Thoracic lymphangiomatosis in childhood is a rare disorder that frequently has poor response to medical therapy as well as a poor prognosis. This disease is often misdiagnosed, and a definitive diagnosis is usually delayed because of the rarity and slow course of the disease. No previous reports have so far described the usefulness of lymphoscintigraphy in the diagnosis of lymphangiomatosis, although some authors have reported the efficacy of lymphoscintigraphy for evaluating chylothorax. A 6-year-old boy presented with a diffuse mediastinal mass and received an open mediastinal biopsy for a definitive diagnosis, which led to the occurrence of massive chylothorax postoperatively. A diagnosis of lymphangiomatosis was finally made based on the lymphoscintigraphic findings demonstrating an obstruction of the thoracic duct. This report describes a rare case of thoracic lymphangiomatosis diagnosed at autopsy, and suggests that the minimally invasive technique of lymphoscintigraphy should be employed to obtain a definitive diagnosis at an early stage.

The herbal medicine daikenchuto ameliorates an impaired anorectal motor activity in postoperative pediatric patients with an anorectal malformation--a pilot study.

Fecoflowmetry (FFM) has been introduced to simulate natural anorectal evacuation. So far, few reports have described the effect of the herbal medicine Daikenchuto (DKT) on impaired anorectal motor function. The aim of this pilot study was to assess anorectal motor function by FFM in postoperatively impaired patients with an anorectal malformation (ARM) before and after administration of DKT. Six postoperative patients with ARM (mean age, 7.8 years) who complained of intractable constipation with soiling in spite of administration of magnesia as a laxative were assessed over an extended period. These patients received 0.3 g/kg/d of DKT for an average of 128 days. Evacuative rate and maximum fecal stream flow were seen to increase significantly after administration of DKT when compared with values before administration of DKT. In conclusion, DKT had a favorable clinical effect on anorectal motor function in postoperative patients with ARM.

Perioperative reactive oxygen species in infants with biliary atresia: A retrospective observational study.

Biliary atresia (BA) is a devastating cholestatic disorder of infants that presents during the first several months after birth due to an idiopathic obstruction to the bile flow. Without prompt diagnosis, Kasai portoenterostomy, and deliberate follow-ups, the resulting cholestasis leads to progressive hepatic failure. Oxidative stress is an abnormal phenomenon inside cells or tissues caused by a disturbance in the reactive oxygen species (ROS). We aimed to measure perioperative ROS in BA patients.Data are presented as median (25th, 75th percentiles). We evaluated 15 BA patients (age 55 [48, 69] days) and measured ROS; serum superoxide dismutase (SOD), urinary 8-iso prostaglandin F2α (8-iso-PGF2α) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) preoperatively and 30 days later to compare values with serum liver function tests and histologic grades of liver cholestasis. For compared BA patients, 4 normal subjects as control group (age 55 [27, 75] days) measured ROS and serum liver function tests.In BA patients, the preoperative serum SOD was 6.1 IU/mL (4.7, 7.2), urinary 8-iso-PGF2α was 1969 pg/mg Cre (1697, 2374), and urinary 8-OHdG was 37.1 ng/mg Cre (33.1, 53.7). At the postoperative day 30, the serum SOD was 5.2 IU/mL (4.2, 6.7), urinary 8-iso-PGF2α was 1761 pg/mg Cre (1256, 3036), and urinary 8-OHdG was 42.1 ng/mg Cre (29.65, 72.64). In ROS, there were no significant differences between the 2 periods. In control group, urinary 8-iso-PGF2α was significantly lower than that in preoperative BA patient group. However, other ROS were not significant differences between control group and BA patient group. The concentration of urinary 8-iso-PGF2α was positively correlated with total bilirubin and direct bilirubin levels (preoperatively: r = 0.6921, P = .0042 and r = 0.6639, P = .007, postoperatively: r = 0.6036, P = .0172 and r = 0.6464, P = .0092, respectively). The preoperative ROS were not correlated with histologic grades of liver cholestasis. Various factors such as liver inflammation, lipid malabsorption, and tissue disorders due to jaundice might affect the antioxidant activity and elevated urinary 8-iso-PGF2α. However, at least until 30 days later, urinary 8-OHdG as oxidative DNA damage might persist after the operation whether the cholestasis improved or not.

Functional assessment of the patients with perineal and vestibular fistula treated by anterior sagittal anorectoplasty.

BACKGROUND: Anterior sagittal anorectoplasty (ASARP) has been a standardised operative treatment for anorectal malformation (ARM). This retrospective study was undertaken to evaluate patients with perineal fistula (PF) and vestibular fistula (VF) treated by ASARP in our institution. PATIENTS AND METHODS: Twenty patients (PF, n = 14; male, n = 8 and female, n = 6 and VF, n = 6) were evaluated. Eighteen patients underwent primary ASARP without protective colostomy. Two patients underwent colostomy because of intestinal atresia and suspected of other type ARM. The age range of operation was from 4 months to 5.0 years. Sixteen patients (PF, n = 13; male, n = 7 and female n = 6 and VF, n = 3) over 3 years of age were evaluated according to the Krickenbeck classification. RESULTS: Operative complications occurred in one patient. Minor wound dehiscence occurred in six patients. Mucosal prolapse occurred in two patients. According to the Krickenbeck classification, amongst male patients with PF, all patients had voluntary bowel movements (VBMs) and two patients had Grade 1 soiling, while four patients had Grade 2 constipation. Amongst female patients with PF, all patients had VBM and no soiling, one patient had Grade 1 and two patients had Grade 2 constipation. In patients with VF, one patient was continent with Grade 1 soiling. One patient had Grade 2 and two patients had Grade 3 constipation. CONCLUSIONS: ASARP without colostomy carried a risk of wound dehiscence. The ASARP technique provided normal or moderate outcomes for VBM and soiling. However, in about half of patients, defecation management with laxative therapy was required to achieve a normal condition.

The characteristics of salivary pepsin in patients with severe motor and intellectual disabilities.

PURPOSE: The aim of the present study was to determine the utility of measuring the salivary pepsin level (SPL) as an objective assessment of gastroesophageal reflux disease (GERD) in severe motor and intellectual disabilities (SMID) patients. SUBJECTS AND METHODS: This prospective study included 26 SMID patients who underwent simultaneous 24-h multichannel intraluminal impedance pH measurement (pH/MII) and SPL evaluation. The enrolled patients were divided into GERD (+) or GERD (-) groups according to the pH/MII findings. The age, gender and pH/MII parameters were compared between the two groups. A correlation analysis was also conducted for the SPL following early-morning fasting and post-enteral feeding and the age, gender, presence of gastrostomy and tracheostomy and pH/MII parameters. The SPL was compared between the two sampling groups. RESULTS: Fifteen patients were classified as GERD (+), and 11 patients were classified as GERD (-). The mean SPL following early-morning fasting and post-enteral feeding among all patients were 104.3 (median: 38, 25th and 75th percentile: 12, 361) ng/ml and 222.2 (median: 152:0, 500) ng/ml, respectively. Regarding positivity, 76.9% and 73.1% of SPL values in early-morning fasting and post-enteral feeding SMID patients, respectively, were positive (≧16ng/ml). The SPL following early-morning fasting demonstrated a weak but significant positive correlation with age. In contrast, we noted no correlation between the pH/MII parameters and the SPL for either the early-morning fasting or post-enteral feeding patients, and no significant difference in the SPL was observed between the GERD (+) and (-) patients. CONCLUSIONS: The present study showed that a high proportion of SMID patients had a relatively high SPL, regardless of the presence of GERD. The SPL in SMID patients might be affected by several distinctive factors in addition to gastroesophageal reflux.

The utility of a phase angle analysis in patients with severe motor and intellectual disabilities.

PURPOSE: The purpose of the present study was to evaluate whether evaluating the phase angle (PhA), in a bioelectrical impedance analysis (BIA) is useful for estimating the nutritional status of severe motor and intellectual disabilities (SMID) patients. SUBJECTS AND METHODS: This retrospective study included 31 SMID patients (mean age: 33.9±13.5years, median age: 29years (range: 18-58years), male/female: 23/8). First, each of the parameters from the total study population and the male and female SMID patients were compared with those of healthy Asian subjects. Second, correlation analyses were conducted to investigate the correlation between the PhA and the other BIA parameters (appendicular skeletal muscle mass index (ASMI), appendicular muscle mass (AMM), extracellular water (ECW)/total body water (TBW)) as well as subjective global assessment and serum nutritional markers. Finally, all patients were divided into 2 groups according to their albumin (Alb) (<3.5 or ≥3.5) values and PhA of the 2 groups were compared. RESULTS: The mean PhA and ASMI were a considerably low, whereas ECW/TBW was considerably high in comparison to the healthy Asian subjects. Significant negative correlations were observed between the PhA and ECW/TBW, whereas there were significant positive correlations between PhA and AMM, ASMI, total protein and albumin levels. Furthermore, PhA of Alb ≥3.5 group was significantly higher than that of Alb <3.5 group. CONCLUSIONS: The present study indicated that SMID patients demonstrate the low PhA, which were similar to sarcopenia and a certain proportion of them also potentially have nutritional disturbances.

Severe Delayed Gastric Emptying Induces Non-acid Reflux up to Proximal Esophagus in Neurologically Impaired Patients.

BACKGROUND/AIMS: The aim of this study is to investigate the degree of delayed gastric emptying (DGE) and evaluate how the severity of DGE affects gastroesophageal reflux disease (GERD) in neurologically impaired (NI) patients utilizing 24-hour multichannel intraluminal impedance pH measurements (pH/MII) and 13C-acetate breath test (13C-ABT) analyses. METHODS: 13C-ABT and pH/MII were conducted in 26 NI patients who were referred to our institution due to suspected GERD. At first, correlation analyses were performed to investigate the correlation between the 13C-ABT parameters and the clinical or pH/MII parameters. Thereafter, all patients were divided into 2 groups (DGE and severe DGE [SDGE] group) according to each cut off half emptying time (t1/2, 90-170 minutes). Each pH/MII parameter was compared between the 2 groups in each set-up cutoff t1/2. RESULTS: The mean t1/2 of all patients was 215.5 ± 237.2 minutes and the t1/2 of 24 (92.3%) patients were > 100 minutes. Significant moderate positive correlations were observed between both t1/2 and lag phase time and the non-acid reflux related parameters. Furthermore, the patients in the SDGE group demonstrated higher non-acid reflux related parameters than those of the DGE groups when the cutoff was t1/2 ≥ 140 minutes. CONCLUSION: The present study demonstrated that GE with t1/2 ≥ 140 minutes was related to an increase of non-acid exposure reaching up to the proximal esophagus in NI patients, and indicating that NI patients with SDGE might have a high risk of non-acid GERD.