Postoperative pharmacotherapy for patients with biliary atresia in Japan.

BACKGROUND: Members of the Japanese Biliary Atresia Society were surveyed using questionnaires that assess their current practice regarding postoperative pharmacotherapy for outpatients with biliary atresia (BA). METHODS: In September 2018, questionnaires were sent to 100 member institutions of the Japanese Biliary Atresia Society. Questionnaires included the number of BA outpatients per institution and pharmacotherapy for outpatients with native liver. Pharmacotherapies were categorized into antibiotics, cholagogues, hepatoprotective agents, branched-chain amino acid supplement, Japanese Kampo medicine, probiotics, laxative, glycerin enema, and "others." In each category, the questionnaires asked about the medicine's details and the time of withdrawal of administration. RESULTS: Responses were collected from 58 of the 100 institutions. Fifty-four institutions (94.7%) had prescribed one or more medicines as postoperative pharmacotherapy, and three institutions (5.3%) did not prescribe any medicines. Fifty-three institutions (93.0%) had prescribed ursodeoxycholic acid (UDCA), and 32 (60.4%) of these continued prescribing UDCA as long as the condition of patients remained unchanged. Twenty-nine (50.9%) had prescribed Japanese Kampo medicines ("Inchinkoto" in all cases). Twenty-four (42.1%) had prescribed antibiotics, mainly trimethoprim-sulfamethoxazole, in 21 (87.5%). Twenty-three (40.4%) had prescribed probiotics. CONCLUSIONS: There were many variations of pharmacotherapy in BA outpatients with native liver in Japan, including antibiotic, probiotic, and Inchinkoto prescriptions. Of the various drugs, the most commonly administered was UDCA.

Quality of life of caregivers supporting neurologically impaired patients who underwent surgery.

BACKGROUND: A questionnaire survey was conducted to clarify whether surgical treatments performed by a pediatric surgeon improve the quality of life (QOL) of caregivers (medical doctors, nurses, physical therapists, and nursery teachers) supporting neurologically impaired (NI) patients who work at specialized institutions. METHODS: The questionnaire survey was conducted with caregivers who cared for NI patients who underwent an operation at the Department of Pediatric Surgery, Kurume University Hospital. Quality-of-life related responses concerning the change of care after surgical procedures in NI patients were collected in addition to the background data related to caregivers and the surgical procedures performed for them. Degrees of difficulty in caring for NI patients and of the caregivers' own QOL postoperatively were also compared. RESULTS: There were 192 valid responses. The majority of responses were from females and nurses aged in their 40s and 50s. The surgical procedure performed most often in the NI patients was gastrostomy. Of the respondents, 77% answered that the postoperative care became easier. The degrees of difficulty in caring for NI patients and the caregivers' own QOL were significantly higher and lower, respectively, among physical therapists compared with caregivers in other occupations. Moreover, the QOL in respondents with factors related to a longstanding relationship with NI patients was significantly higher compared with the respondents without them. CONCLUSION: This survey indicated that surgical procedures for NI patients might contribute to improved QOL for the caregiver by reducing the difficulty of caring for NI patients.

Current status of intractable pediatric gastroesophageal reflux disease in Japan: a nationwide survey.

PURPOSE: A nationwide survey was conducted to investigate the current status of pediatric gastroesophageal reflux disease (GERD) in Japan, with special reference to the characteristics of intractable GERD. METHODS: Data were collected using a questionnaire from facilities specializing in the treatment of pediatric GERD in Japan. Intractable GERD was defined as follows: I, no symptomatic improvement after 8 weeks of optimal medical treatment (OMT) plus fundoplication; II, no symptomatic improvement after 8 weeks of OMT and with no indications for fundoplication; and III, no symptomatic improvement after surgery without OMT. RESULTS: We collected data from 3,463 pediatric patients with GERD from 91 institutions, and 81 satisfied the definition of intractable GERD. Additional clinical information was obtained from 56 patients, and 41 represented cases of definite intractable GERD. The main underlying disorders included neurological impairment (NI), esophageal atresia (EA), and congenital heart disease (CHD), which altogether accounted for 85% of patients. Of the 41 patients, 33 received fundoplication, and the remaining 8 received medical treatment alone because surgery was considered unsuitable. CONCLUSIONS: The nationwide survey revealed that pediatric intractable GERD is rare in Japan. Three main underlying disorders-NI, EA, and CHD-were implicated in the majority of cases of intractable GERD.

Influence of laparoscopy-aided gastrostomy on gastroesophageal reflux in neurologically impaired patients using multichannel intraluminal impedance pH measurements.

BACKGROUND: Development of gastroesophageal reflux disease (GERD) after gastrostomy remains debatable. Therefore, this study aimed to evaluate whether laparoscopy-aided gastrostomy (LAG) influence on the occurrence of GERD in neurologically impaired (NI) patients. Furthermore, we investigated whether preoperatively excluding NI patients with GERD can reduce the number of patients requiring subsequent anti-reflux surgery (ARS) after LAG. METHODS: This retrospective study included 35 NI patients (median age: 11.0; interquartile range 5.0-23.5 years) who underwent LAG according to our criterion from October 2012 to June 2020 and MII-pH before and after LAG. MII-pH parameters were compared in all patients and among three age groups between before and after LAG. RESULTS: There were no significant differences in MII-pH parameters before and 1 year after LAG in all patients, and no patient underwent subsequent ARS. Only one paediatric patient with 64 number of reflux episodes before LAG required subsequent ARS 3 years after LAG. CONCLUSIONS: Generally, LAG did not influence the postoperative GERD at 1 year after LAG, and our criteria could reduce the number of patients requiring subsequent ARS. However, paediatric NI patients with higher number of reflux episodes in preoperative MII-pH study may need careful long-term follow-up after LAG.

Complications in patients with neurological impairment after gastrostomy.

BACKGROUND: Neurological impairment (NI) is responsible for most conditions that require a permanent gastrostomy tube. The present study assessed the occurrence of short- and long-term complications after video-assisted gastrostomy (VAG) in patients with NI. METHODS: The incidence of short- (<6 months) and long-term (over 2 years) complications of VAG were analyzed in a retrospective study. The differences between the incidence of the complications of VAG according to the age at surgery (≤15 years vs. ≥16 years) were also evaluated. The short- and long-term complications observed were granulation tissue formation, infection requiring antibiotic treatment, skin problems, perigastrostomy leakage, vomiting, accidental tube dislodgement, dumping syndrome, ileus, and peritonitis. RESULTS: Eighty-two patients were evaluated for short- and long-term complications. The long-term complication rate was significantly lower than the short-term complication rate (P = 0.0026). Onodera's prognostic nutritional index before VAG in patients with long-term complications was significantly lower than in patients without such complications (P = 0.046). The incidence of long-term granulation tissue formation, infection, and vomiting were significantly lower than those of similar short-term complications. Long-term skin problems were associated with short-term skin problems (odds ratio: 18.95; 95% confidence interval: 4.53-92.98; P < 0.001). The number of patients ≥16 years old with short- and long-term skin problems was significantly higher than in patients ≤15 years old (P = 0.0014 and P = 0.0073, respectively). CONCLUSIONS: The incidence rate of granulation tissue formation and infection after VAG were lower in the long term than in the short term. However, patients ≥16 years old presented with persistent complications.

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.

The assessment of the esophageal motility of children with esophageal disorders by the detailed observation of the pH-multichannel intraluminal impedance waveform and baseline impedance: screening test potential.

BACKGROUND: The present study aimed to evaluate whether the detailed observation of pH/MII waveforms and the analysis of baseline impedance (BI) values could detect esophageal dysmotility in pediatric patients with esophageal disorders. PATIENTS AND METHODS: Eleven patients with congenital esophageal disorder in whom pH/MII was conducted from April 2011 to June 2015, were enrolled in this study. The diagnoses of the patients were as follows: postoperative esophageal atresia (EA), n = 6; esophageal achalasia (EAch), n = 4; and congenital esophageal stenosis (CES), n = 1. The characteristics of the pH/MII waveform, pathological GERD, BI value, and the average BI value of the 2 distal channels (distal BI; DBI) were analyzed in each disorder. RESULTS: Two EA (33%) patients and one EAch (25%) patient were diagnosed with GERD. The mean DBI values of the EA, EAch and CES patients was 912 ± 550, 2153 ± 915 and 1392 Ω, respectively. The EA patients showed consistently low DBI values. One CES patient and two infantile EAch patients showed postprandial prolonged low DBI values. Whereas, the pH/MII waveforms of the adolescent EAch patients were difficult to interpret due to their extremely low BI values. CONCLUSIONS: The present study demonstrated that the detailed observation of the pH/MII waveforms in all channels and the analysis of BI were useful for evaluating esophageal motility in children with congenital esophageal disorders. In particular, infantile patients with EAch showed DBI findings that were distinct from those of adult EAch patients. Considering the difficulty of performing esophageal manometry in young children, the detailed observation of the pH/MII waveform may help in the diagnosis of esophageal dysmotility in children.

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.

Combined repeated-dose and reproductive/developmental toxicity screening test of benzene, 1,1'-oxybis-, tetrapropylene derivs. in rats.

We have conducted animal toxicity tests of chemicals for a chemical safety program implemented by the Ministry of Economy, Trade and Industry of Japan. Here we conducted a combined repeated-dose and reproductive/developmental toxicity screening test of benzene, 1,1'-oxybis-, tetrapropylene derivs. (BOTD). BOTD was administered to 9-week-old Crl:CD(SD) male and female rats by gavage at 0, 40, 200, or 1000 mg/kg/day. Males were treated for 42 days including mating period. Females were treated for 42-53 days through the premating, mating, pregnancy, and until Day 4 of lactation periods. Increases in prothrombin time and activated partial thromboplastin time values were observed only in males at 200 and 1000 mg/kg/day. Hypertrophy of centrilobular hepatocytes was observed with increased liver weight in both sexes at 200 and 1000 mg/kg/day, but there was no histologic evidence of hepatotoxicity. Diffuse hypertrophy of follicular cells in thyroid glands was observed in females at 200 mg/kg/day and in both sexes at 1000 mg/kg/day, with an increased blood cholesterol level in females at 1000 mg/kg/day. The conception index was decreased for females at 1000 mg/kg/day; and no abnormalities were detected in the reproductive indices of implantation, delivery, or pups' condition, although a slight increase in the pups' body weight was noted at birth. Our data indicate a no-observed-adverse-effect level of 40 mg/kg/day for repeated-dose toxicity on the basis of the prolongation of blood coagulating time, and of 200 mg/kg/day for reproductive/developmental toxicity on the basis of the decreased conception index.

Pharmacotherapy for pediatric chronic intestinal pseudo-obstruction: Nationwide survey in Japan.

BACKGROUND: Chronic intestinal pseudo-obstruction (CIPO) is a rare disabling and life-threatening disorder characterized by severe impairment of gastrointestinal peristalsis. While a number of pharmacotherapeutics have been developed, only a few trials have been carried out for improvement of the pathological condition of CIPO patients. This report describes the results of a nationwide survey on the pharmacotherapy used in pediatric CIPO in Japan. METHODS: In 2012, a nationwide survey was conducted to identify the clinical presentation of CIPO in Japan. Information was gathered on pharmacotherapy. Four categories were created for medicines used in pharmacotherapy: "probiotics", "Japanese herbal medicines (Kampo medicines)", "laxatives", and "prokinetics". RESULTS: Ninety-two responses were collected from 47 facilities. Of the 62 patients who met the diagnostic criteria, 52 were treated with medications, while the remaining 10 were not. Thirty-four patients were given a total of 49 probiotics; 39 were treated with a total of 50 Kampo medicines; 20 were treated with a total of 28 laxatives; and 26 were given a total of 30 prokinetics, 70% of whom were treated specifically with mosapride. CONCLUSION: Traditional Japanese medicines such as Kampo medicines and mosapride are often used to treat CIPO in Japan. Two combinations, that is, probiotics and Kampo medicines; and Kampo medicines and prokinetics, were often used for pediatric CIPO in Japan.

Combined repeated-dose and reproductive/developmental toxicity screening test of 1-tert-butoxy-4-chlorobenzene in rats.

We have carried out animal toxicity tests of chemicals for a chemical safety program implemented by the Ministry of Economy, Trade, and Industry of Japan. Here, we tested 1-tert-butoxy-4-chlorobenzene in a combined repeat-dose and developmental and reproductive toxicity test. The test chemical was administered daily by gavage to 9-week-old Crl:CD (SD) rats at doses of 0, 20, 100, and 500 mg/kg/d. Males were treated for 42 d beginning 14 d before mating. Females were treated from 14 d before mating to day 4 of lactation. Decreased spontaneous locomotion, decreased respiratory rate, and incomplete eyelid opening were observed at 500 mg/kg/d (both sexes), but resolved within 30 min of administration, suggesting central nervous system depression. No notable changes were observed in body weight, food consumption, functional battery tests, or blood test. Increased liver weight with centrilobular or diffuse hepatocyte hypertrophy was observed at 100 and 500 mg/kg/d (both sexes). There were no biochemical or histopathological changes related to hepatotoxicity. Increased kidney weight with basophilic tubules, tubule dilatation, and increased hyaline droplets were observed in males dosed at 100 and 500 mg/kg/d. Immunohistochemical staining indicated α2u-globulin nephropathy, a male rat-specific toxicity. Although kidney weight was also increased in females dosed at 500 mg/kg/d, it was not considered to be an adverse effect because there were no histopathological changes. Pup weights on postnatal day 0 were decreased at 500 mg/kg/d and still decreased on postnatal day 4. Our data indicated the no-observed-adverse-effect-level for repeated-dose and reproductive/developmental toxicity for 1-tert-butoxy-4-chlorobenzene was 100 mg/kg/d.

Effects of dose volume and delivery device on bronchoalveolar lavage parameters of intratracheally administered nano-sized TiO2 in rats.

The intratracheal (IT) test is useful for screening the pulmonary toxicity of inhaled materials, including nanomaterials. However, a standard procedure has not yet been authorized internationally, and the effects of different test parameters are unknown. To determine appropriate experimental conditions for the IT test, we intratracheally administered nano-sized TiO2 to male F344 rats at 3.0 mg/kg body weight by using two delivery devices (gavage needle or microaerosolizer) and dose volumes of 0.5-3.0 mL/kg (gavage needle) or 0.5-2.0 mL/kg (microaerosolizer). We evaluated the pulmonary deposition and interlobar distribution of TiO2 at both 30 min and 3 days after administration. In addition, the inflammatory components in bronchoalveolar lavage (BAL) fluid were measured 3 days after administration of TiO2. At dose volumes of 0.5-2.0 mL/kg, the BAL values were comparable regardless of the device used. In addition, pulmonary TiO2 burden and lobar concentration patterns were equivalent at all combinations of dose volume and delivery device. In conclusion, the acute pulmonary toxicity of nanomaterials can be assessed effectively by using an IT test in which the test agent is provided to rats at a dose volume of 0.5-2.0 mL/kg with either a gavage needle or microaerosolizer.

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.

Outcomes of nonrejection in weakly fluorescent intestine detected by indocyanine green fluorescence angiography: a case series of infants.

BACKGROUND: Indocyanine green fluorescence angiography, a validated noninvasive imaging technique, is used to assess tissue vascularization. Here, we report three infant patients who underwent intraoperative indocyanine green fluorescence angiography and suffered from postoperative complications caused by the lack of weak fluorescent intestinal resection and assessed residual intestinal perfusion. CASE PRESENTATION: We observed the clinical characteristics and operative findings of patients treated from January 2022 to December 2022. Indocyanine green (0.5 mg/kg) was intravenously injected. The first patient was a 29-day-old girl with surgical necrotizing enterocolitis who underwent intraoperative indocyanine green fluorescence angiography at the first- and second-look operations. The proximal jejunum was difficult to diagnose to detect blood flow during the second-look operation. The second patient was a 32-day-old boy with surgical necrotizing enterocolitis. A part of the antimesenteric mucosa of the patient that exhibited weak fluorescence was preserved; however, it formed postoperative hematomas. The third patient was a 30-day-old boy with midgut volvulus. Weak fluorescence in the intestinal wall was observed 5 cm of the small intestine from the ileocecal valve was preserved, but it formed a stricture, and the patient underwent ileocecal resection after 30 days. CONCLUSIONS: Weak fluorescence in the intestine in infants by performing indocyanine green fluorescence angiography is associated with a high risk of non-recovering ischemic lesions and postoperative complications.

The Evaluation of Gastric Emptying Using the 13 C-Acetate Breath Test in Neurologically Impaired Patients - A Focus on the Stomach Function and Morphology.

PURPOSE: We explored factors affecting gastric emptying in neurologically impaired (NI) patients using the 13C-acetate breath test. METHODS: Twenty-four NI patients were classified by the presence of gastroesophageal reflux disease (GERD), which was treated by fundoplication plus gastrostomy, or the absence of GERD, which was treated by gastrostomy alone, along with gastric malposition involving cascade stomach and organoaxial gastric volvulus (OGV). Gastric emptying parameters (GEPs), which were the emptying half time (T 1/2 , minute), the lag phase time (T lag , minute), and the gastric emptying coefficient (GEC), were measured before and after surgery. We evaluated the relationship between GEPs and GERD, gastric malposition, and surgical intervention. All data were expressed as the median (interquartile range). RESULTS: The T1/2 and GEC of patients with OGV were significantly worse than in those without OGV before surgery (T1/2 with OGV: 241.3 [154.9, 314.3] vs. T1/2 without OGV: 113.7 [105.2, 151.4], p = 0.01, GEC with OGV: 3.19 [2.46, 3.28] vs. GEC without OGV: 3.65 [3.24, 3.90], p = 0.02). GERD and cascade stomach were not associ ated with GEPs. The GEPs of all NI patients showed no significant difference between before and after surgery. The surgical change in T1/2 (ΔT 1/2 ) in the patients with OGV was significantly lower than in those without OGV (ΔT1/2 with OGV: -47.1 [-142.7, -22.1] vs. ΔT1/2 without OGV: -3.78 [-26.6, 12.0], p = 0.03). CONCLUSION: Stomach malposition, such as OGV, seems to affect gastric emptying and may be improved by surgi cal intervention.