Successful outcome with oral sirolimus treatment for complicated lymphatic malformations: a retrospective multicenter cohort study.

Purpose: Sirolimus has emerged as a safe and effective treatment for complicated lymphatic malformations (LMs). We aim to prove the effectiveness and safety of sirolimus as a therapeutic option for patients with complicated LMs. Methods: Fifty-eight patients with complicated LMs treated with sirolimus for at least 6 months at multicenter between July 2018 and January 2023 were enrolled. All patients were administered oral sirolimus starting at 0.8 mg/m2 every 12 hours, with target serum concentration levels of 8-15 ng/mL. Evaluation for clinical symptoms and LMs volume on MRI were reviewed to assess treatment response and toxicities. Evaluation of disease response was divided into 3 values: complete response, partial response (significant, moderate, and modest), and progressive disease. Results: The median age at the initiation of sirolimus treatment was 6.0 years (range, 1 month-26.7 years). The median duration of treatment was 2.0 years (range, 6 months-4.4 years). The most common lesions were head and neck (25 of 58, 43.1%). Forty-six patients (79.3%) demonstrated a reduction in LMs volume on MRI or improvement of clinical symptoms including 2 complete responses. The young age group and the patients who underwent few prior therapies showed better responses. None of the patients had toxicities attributable to sirolimus with a Common Terminology Criteria for Adverse Events grade of ≥3. Conclusion: Oral sirolimus treatment brought a successful outcome without severe adverse effects. It could be the first-line therapy, especially for the young age group of complicated LMs, and an additional option for refractory lesions that did not respond to conventional treatment.

Optimal timing for inguinal hernia repair in premature infants: surgical issues for inguinal hernia in premature infants.

Purpose: We analyzed the timing of inguinal hernia repair in premature infants in the neonatal intensive care unit (NICU) considering recurrence, incarceration, and other complications. Methods: In this multicenter retrospective review, premature infants (<37 weeks) in the NICU diagnosed with inguinal hernia between 2017 and 2021 were segregated into 2 groups based on the timing of inguinal hernia repair. Results: Of 149 patients, 109 (73.2%) underwent inguinal hernia repair in the NICU and 40 (26.8%) after discharge. Preoperative incarceration did not differ, but complications with recurrence and postoperative respiratory insufficiency were higher in the NICU group (11.0% vs. 0%, P = 0.029; 22.0% vs. 5.0%, P = 0.01). Multivariate analysis showed that the significant factors affecting recurrence were preoperative ventilator dependence and body weight of <3,000 g at the time of surgery (odds ratio [OR], 16.89; 95% confidence interval [CI], 3.45-82.69; P < 0.01 and OR, 9.97; 95% CI, 1.03-95.92; P = 0.04). Conclusion: Our results suggest that when premature infants are diagnosed with inguinal hernia in the NICU, inguinal hernia repair after discharge may decrease the odds of recurrence and postoperative respiratory insufficiency. In patients who have difficulty delaying surgery, it is thought that surgery should be performed carefully in a ventilator preoperatively or weighed <3,000 g at the time of surgery.

Comparison of splenic vessel preserving distal pancreatectomy and the Warshaw technique for solid pseudopapillary neoplasm in children.

PURPOSE: Spleen-preserving distal pancreatectomy (SPDP) such as splenic vessel preservation (SVP) for solid pseudopapillary neoplasms (SPNs) in the body or tail of the pancreas in children prevents post-splenectomy infection and hematologic disorders. However, SVP could be technically challenging, and the Warshaw technique (WT) could be an alternative technique that has been reported to be safe and effective in adults. We, therefore, compared the perioperative outcomes of SVP and WT in pediatric patients. METHODS: We retrospectively reviewed the medical records of pediatric patients with SPN who underwent SPDP using SVP or WT between November 2002 and November 2018 at a large-sized tertiary referral center. RESULTS: Twenty-eight patients were included. Sixteen (57.1%) patients underwent SVP and 12 (42.9%) patients underwent WT. There were no significant differences in the baseline characteristics between the two groups. Postoperative complications occurred in 8 patients each in the SVP (50%), and the WT (66.7%) groups. Two (12.5%) in the SVP group and 1 (8.3%) in the WT group required additional intervention. During a median follow-up duration of 49 months, there were no significant differences in the incidence of splenic infarctions or perigastric varices between the two groups. CONCLUSIONS: There were no significant differences in the surgical outcomes between WT and SVP in pediatric patients with SPN. WT could be a safe and feasible alternative technique for SVP in challenging cases.

Prenatal prognostic factors for isolated right congenital diaphragmatic hernia: a single center's experience.

BACKGROUND: Right-sided congenital diaphragmatic hernia (RCDH) is relatively rare compared with left-sided congenital diaphragmatic hernia (LCDH). Clinical data of RCDH, especially with respect to antenatal prediction of neonatal outcome, are lacking. The aim of this study was to report the treatment outcomes of patients with antenatally diagnosed RCDH and to evaluate the predictability of observed-to-expected lung area-to-head circumference ratio (O/E LHR) for perinatal outcomes, focused on mortality or extracorporeal membrane oxygenation (ECMO) requirement. METHODS: We retrospectively reviewed the medical records of newborn infants with isolated RCDH. We analyzed and compared the clinical and prenatal characteristics including the fetal lung volume, which was measured as the O/E LHR, between the survivors and the non-survivors. RESULTS: A total of 26 (66.7%) of 39 patients with isolated RCDH survived to discharge. The O/E LHR was significantly greater in survivors (64.7 ± 21.2) than in non-survivors (40.5 ± 23.4) (P =.027). It was greater in survivors without ECMO requirement (68.3 ± 15.1) than non-survivors or those with ECMO requirement (46.3 ± 19.4; P = .010). The best O/E LHR cut-off value for predicting mortality in isolated RCDH was 50. CONCLUSIONS: The findings in this study suggest that O/E LHR, a well-characterized prognostic indicator in LCDH, could be applied to a fetus with antenatally diagnosed RCDH. A large cohort study is required to verify the association between O/E LHR values and the graded severity of RCDH.

Effects of sirolimus in the treatment of unresectable infantile hemangioma and vascular malformations in children: A single-center experience.

OBJECTIVE: Recently, sirolimus has emerged as a safe and effective treatment modality for unresectable vascular lesions. In the present study, we investigated the effectiveness and safety of sirolimus from our early experience with patients with unresectable vascular anomalies. METHODS: The medical records and radiologic images of all patients with unresectable vascular anomalies treated with sirolimus at our center from January 2018 to November 2019 were retrospectively reviewed. All patients were administered oral doses of sirolimus 0.8 mg/m2 every 12 hours as the initial dose, followed by maintenance of a target serum concentration (5-10 ng/mL) with therapeutic drug monitoring. RESULTS: Six patients with unresectable vascular anomalies were treated with sirolimus for ≥10 months. Their median age at the initiation of sirolimus treatment was 17 months (range, 8-67 months). The median duration of treatment was 13 months (range, 10-16 months). One patient had a good response, four had an intermediate response, and one had no response to sirolimus therapy. None of the patients had discontinued sirolimus therapy because of adverse effects. CONCLUSIONS: Sirolimus can be used effectively and safely for patients with unresectable vascular anomalies. However, further prospective studies are warranted to evaluate the long-term effects of sirolimus and clarify the indications for early intervention.

Functional and structural evaluation in the lungs of children with repaired congenital diaphragmatic hernia.

BACKGROUND: To evaluate the long-term functional and structural pulmonary development in children with repaired congenital diaphragmatic hernia (CDH) and to identify the associated perinatal-neonatal risk factors. METHODS: Children with repaired CDH through corrective surgery who were born at gestational age ≥ 35 weeks were included in this analysis. Those who were followed for at least 5 years were subjected to spirometry and chest computed tomography for evaluation of their functional and structural growth. Main bronchus diameters and lung volumes (total, left/right) were measured. According to total lung volume (TLV) relative to body surface area, children were grouped into TLV ≥ 50 group and TLV < 50 group and the associations with perinatal-neonatal factors were analyzed. RESULTS: Of the 28 children (mean age, 6.2 ± 0.2 years) with left-sided CDH, 7 (25%) had abnormal pulmonary function, of whom 6 (87%) showed restrictive patterns. All pulmonary functions except FEF25-75% were worse than those in matched healthy control group. Worse pulmonary function was significantly associated with small head and abdominal circumferences at birth. The mean TLV was 1339.1 ± 363.9 mL and LLV/TLV was 47.9 ± 2.5 mL. Children with abnormal pulmonary function were more likely to have smaller lung volumes. In multivariate analysis, abdominal circumference at birth was significantly associated with abnormal lung volume. CONCLUSIONS: A quarter of children with repaired CDH showed abnormal pulmonary function. Small abdominal circumference at birth was associated with abnormal pulmonary function and lower TLV. .

The Advantages of Indocyanine Green Fluorescence Imaging in Detecting and Treating Pediatric Hepatoblastoma: A Preliminary Experience.

Background: Currently, indocyanine green (ICG) fluorescence imaging enables radical surgical resection in hepatoblastoma (HB) and has beneficial uses; however, its usage in pediatric patients is still limited. Methods: From 2015 to 2019, 17 hepatoblastoma patients underwent 22 fluorescence-guided surgery using ICG. ICG (0.3 mg/kg) was intravenously injected 24-48 h before the operation. With ICG/NIR camera, intraoperative identification of biological structures and demarcation of mass were conducted. Results: ICG fluorescence-guided surgery was performed for hepatoblastoma in 22 cases: 16, 1, and 2 cases underwent anatomic resection, partial hepatectomy, and liver transplantation, respectively. Six patients accompanied lung metastasis at the time of surgery, and two patients underwent lung surgery using ICG. The median interval from ICG injection to surgery was 38.3 h (range, 20.5-50.3 h). The median tumor size was 36.5 mm (range, 2-132 mm). According to the pathologic finding, the median safety margin was secured for 6 mm (range, 0-11 mm) and there was no residual finding at the liver at the follow-up computed tomography (CT). Conclusions: ICG fluorescence imaging in children with HB was feasible and safe for tumor demarcation and enhancing the accuracy of radical tumor resection.

Usefulness of peritoneal drainage in extremely low birth weight infants with intestinal perforation: a single-center experience.

PURPOSE: Necrotizing enterocolitis and intestinal perforation are the most common surgical emergency in the neonatal intensive care unit. The purpose of this study is to evaluate if peritoneal drainage (PD) is beneficial in extremely low birth weight infants with intestinal perforation. METHODS: Retrospective cohort study of extremely low birth weight infants with a diagnosis of intestinal perforation. They were received primary PD (n = 23, PD group) or laparotomy (n = 13, LAP group). Laboratory and physiologic data were collected and organ failure scores calculated and compared between preprocedure and postprocedures. Data were analyzed using appropriated statistical tests. RESULTS: Between January 2005 and December 2015, 13 infants (male:female = 9:4) received laparotomy. Of 23 infants (male:female = 16:7) received PD, 20 infants received subsequent laparotomy. There were no demographic differences between PD and LAP groups. And there were no differences in total organ score in either group (PD, P = 0.486; LAP, P = 0.115). However, in LAP group, respiratory score was statistically improved between pre- and postprocedure organ failure score (P = 0.02). In physiologic parameter, PD group had a statistically worsening inotropics requirement (P = 0.025). On the other hand, LAP group had a improvement of PaO2/FiO2 ratio (P = 0.01). CONCLUSION: PD does not improve clinical status in extremely low birth weight infants with intestinal perforation.

Chitosan oligosaccharide (GO2KA1) improves postprandial glycemic response in subjects with impaired glucose tolerance and impaired fasting glucose and in healthy subjects: a crossover, randomized controlled trial.

BACKGROUND: The antidiabetic and hypoglycemic effects of chitosan have been reported in previous studies. We have previously shown that chitosan oligosaccharide reduces postprandial blood glucose levels in vivo. We conducted a short-term crossover study to support the results of the previous study. METHODS: The study was a randomized, double-blind, controlled crossover trial completed at one clinical research site. Subjects with impaired glucose tolerance and impaired fasting glucose and healthy subjects were randomly assigned to consume one of two different experimental test capsules that differed in only the sample source (GO2KA1 vs placebo), and all subjects were instructed to consume the 75 g sucrose within 15 min. After a 7-day interval, the subjects consumed the other capsules that were not consumed on the first day. We assessed blood glucose levels using a 2-h oral sucrose tolerance test. The study was registered at clinicaltrials.gov (NCT03650023). RESULTS: The test group showed significantly lower blood glucose levels at 60 min (p = 0.010) and postprandial blood glucose areas under the curve (p = 0.012). The change in blood glucose levels at 60 min was significantly lower in the test group than in the placebo group (p = 0.017). CONCLUSIONS: Based on the results of this study, the consumption of chitosan oligosaccharide (GO2KA1) supplements with a meal can effectively reduce postprandial blood glucose levels, which is relevant to the prevention of diabetes.

How to safely perform laparoscopic liver resection for children: A case series of 19 patients.

PURPOSE: The purpose of this study was to determine the feasibility and outcome of laparoscopic hepatectomy in pediatric patients with liver tumors and introduce surgical techniques to minimize complications. METHODS: This was a retrospective study of 19 patients less than the age of 18 years old who underwent LLR for liver tumors between November 2005 and May 2017. RESULTS: Ten females and nine males with a median age of 26 months and a median body weight of 14.7 kg were enrolled. Diseases of these patients were hepatoblastoma, neuroblastoma, biliary atresia, and liver abscess. The numbers of resected hepatic segments were more than two in thirteen patients and one in six patients. One patient required conversion to laparotomy to control bleeding caused by injury to the left hepatic vein. Nine patients received transfusions perioperatively. Median duration of operation was 230 min, and median postoperative hospital stay was 7.0 days. There was no postoperative complication. Only one patient showed nonhepatic recurrence of neuroblastoma which caused mortality. CONCLUSIONS: LLR for benign and malignant liver tumors showed acceptable amount of bleeding and low complication rate. Therefore, LLR would be a safe and feasible option for liver tumors in children with proper technical efforts and selection of patients. LEVEL OF EVIDENCE: Level III.

Minimally-invasive neonatal surgery: laparoscopic excision of choledochal cysts in neonates.

PURPOSE: Improvements in surgical techniques and a better understanding of the unique anesthetic requirements in neonates undergoing laparoscopy have suggested that laparoscopic surgery may be effective in newborns. This study therefore evaluated the safety and feasibility of laparoscopic excision of the cyst (LEC) in neonates. METHODS: This retrospective study included 43 neonates who underwent excision of choledochal cysts between November, 2001, and January, 2018, including 21 who underwent open excision and 22 who underwent LEC. Their perioperative and surgical outcomes were reviewed. The patients were followed up for a median 37 months (range, 3-141 months). RESULTS: Baseline characteristics did not differ significantly in the open and LEC groups. Mean intraoperative peak partial pressure of arterial CO2 (PaCO2) (45.5 mmHg vs. 48.0 mmHg) and total operation time (208.3 ± 71.0 minutes vs. 235.0 ± 47.2 minutes) were similar in both groups. Parents of the patients in the LEC group provided a more positive evaluation of scar scale and greater satisfaction with wound. No patient in either group experienced any critical complications. Three patients in the open excision group required readmission for cholangitis and 2 patients had ileus. No patient in the laparoscopic excision group experienced any postoperative complications during follow-up. CONCLUSION: Despite difficulties performing laparoscopic surgery in neonates, LEC was safe and feasible when intraperitoneal peak pressure was maintained under 10 mmHg and PaCO2 was closely monitored by a pediatric anesthesiologist. Compared with open excision, LEC provided improved cosmetic outcomes without severe complications. Prospective randomized studies with large numbers of patients are warranted.

Suggested Indications for Enucleation of Solid Pseudopapillary Neoplasms in Pediatric Patients.

Background: Solid pseudopapillary neoplasms (SPNs) are rare, low-grade, malignant neoplasms that can occur in pediatric patients. Although complete resection of the tumor is the principle treatment, SPN enucleation (EN) has been reported to be effective in children. This study aimed to examine the feasibility and safety of EN by comparing it with conventional pancreatectomy (CP), and to present the indications for its use in pediatric patients. Methods: We retrospectively reviewed the medical records of 66 patients who underwent surgery for SPN at our institution from October 1992 to April 2018. Surgical methods, postoperative complications, hospital stay, and recurrence were compared. Results: Of the 66 patients, 15 (22.7%) were treated with EN and 51 (77.3%) were treated with CP. The mean duration of EN operation was 262 min (±145 min) and of CP was 345 min (±195 min). There was no statistically significant difference between the two methods (P = 0.13). To objectively compare the mass size between patients, we introduced a tumor size/intraperitoneal width ratio, which also revealed no significant difference between the 2 surgery groups (P = 0.21). The EN group had one case of recurrence at the resection site. The complications observed were fluid collection, splenic infarctions, hematomas, pancreatic fistulas, portal vein thromboses, and chylous drainage, among which pancreatic fistulas were the most frequent followed by moderate-severe fistulas in the EN group (P < 0.001). The mean postoperative fasting time (EN 17.0 ± 8.7 days vs. CP 5.1 ± 3.3 days, P < 0.001) and mean hospital stay (EN 23.4 ± 10.0 days vs. CP 13.2 ± 6.5 days, P = 0.002) showed statistically significant differences. Conclusion: Compared with CP treatment, EN of SPNs in children has the disadvantages of prolonged fasting times and hospital stays to recover from moderate pancreatic fistulas. However, if appropriate indications are applied, EN can be considered a safe and effective surgical procedure for children.

Recent Trends in the Clinicopathological Features of Thyroid Nodules in Pediatric Patients: A Single Tertiary Center Experience over 25 Years.

BACKGROUND: The trends in pediatric patients having thyroid nodules have not been well evaluated. Here, we analyzed the clinicopathological features of the children who have presented with thyroid nodules at our center over several decades in order to determine a change of trend. MATERIALS AND METHODS: We analyzed 215 pediatric patients who had undergone a thyroidectomy between 1990 and 2014 at our single tertiary center. The clinicopathological features were analyzed according to age, sex, and the year of diagnosis. RESULTS: The most common reason for hospital admission was a palpable anterior neck mass (76.7%). The males in the patient cohort were younger than the females (13 vs. 15 years old, p < 0.05). The female patients increased from 50.0% to 83.0% with age (p < 0.05). The rate of malignancy did not increase with age (p < 0.05). However, the malignancy rate was higher in the more recently seen patients (23.8% during the early study period and 86.8% in the late study period; p < 0.05). CONCLUSION: Following a thyroidectomy in children with thyroid nodules, there was no change in the rate of detection of thyroid cancer over time with age, although the detected frequency of malignancy has increased in more recent patients. Therefore, early thyroid nodule detection for malignant screening is likely to be required for pediatric patients in the near future.

Complaints addressed by regulatory authorities in drug advertising targeted at consumers: Cases across three, different countries.

BACKGROUND: Misleading advertisements can affect behavior of both consumers and prescribers and may lead to inappropriate use of medications. OBJECTIVE: To analyze the complaints upheld by regulatory authorities in the United Kingdom, Canada, and Australia regarding pharmaceutical advertising directed at consumers. METHODS: Complaints addressed between January 2014 and June 2017 were retrieved from the websites of regulatory authorities. Complaints addressed by self-regulatory bodies were not included due to the poor availability of data. RESULTS: Sixty complaints, 374 complaints, and 223 complaints from the United Kingdom, Canada, and Australia, respectively, were analyzed. In the United Kingdom, the most frequent type of violation was advertising of prescription drugs (70.5%); most of these violations involved botulinum toxin. In Canada, advertising on online media was more likely to be associated with prescription drugs than that on traditional media (P < 0.001). In Australia, advertising of prescription drugs accounted for less than 10% of complaints, but all were associated with online media. CONCLUSIONS: In countries where direct-to-consumer advertising of prescription drugs is prohibited, regulatory authorities may need to devise further strategies to safeguard the public as this is an unresolved issue and is predicted to become more problematic with the increased use of online media.

Half-life of alpha-fetoprotein in neonatal sacrococcygeal teratoma.

BACKGROUND: Alpha-fetoprotein (AFP) is useful as a tumor marker for sacrococcygeal teratoma (SCT). We investigated the half-life of AFP in SCT. METHODS: Neonates who underwent surgical treatment for SCT between 1997 and 2016 were included in the study, whereas patients who died before or after surgery or had malignant germ cell tumors were excluded. RESULTS: Fifty-five non-recurrent SCT patients (M:F = 18:37) were enrolled. They underwent surgery on average 7.4 ±â€¯4.1 days after birth. Serum AFP was measured an average 4.25 ±â€¯2.07 times per patient. We obtained 165 half-lives following the formula (M = Mo * (1/2) Δt/T). A positive correlation was observed between half-life and patient age using the formula T1/2 = 0.0597 × days +6.1643 (p < 0.001). It was different from recurrent SCT (T1/2 = 0.1196 × days -0.0633) (p < 0.05). Half-life was different between mature SCT (T1/2 = 0.0671 × days +4.3912) and immature SCT (T1/2 = 0.0433 × days +8.9339) (p < 0.05). CONCLUSION: The half-life of AFP in neonatal patients with SCT was prolonged in proportion to the age, and it was getting longer in recurrent tumor than non-recurrent tumor. The half-life of AFP was longer in immature teratoma than in mature teratoma. LEVEL OF EVIDENCE: IV.

Rapid estrogen receptor-α signaling mediated by ERK activation regulates vascular tone in male and ovary-intact female mice.

Estrogen has been shown to affect vascular reactivity. Here, we assessed the estrogen receptor-α (ERα) dependency of estrogenic effects on vasorelaxation via a rapid nongenomic pathway in both male and ovary-intact female mice. We compared the effect of a primary estrogen, 17ß-estradiol (E2) or 4,4',4″-(4-propyl-[1H]pyrazole-1,3,5-triyl)tris-phenol (PPT; selective ERα agonist). We found that E2 and PPT induced greater aortic relaxation in female mice than in male mice, indicating ERα mediation, which was further validated by using ERα antagonism. Treatment with 1,3-bis(4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy)phenol]-1H-pyrazole dihydrochloride (MPP dihydrochloride; ERα antagonist) attenuated PPT-mediated vessel relaxation in both sexes. ERα-mediated vessel relaxation was further validated by the absence of significant PPT-mediated relaxation in aortas isolated from ERα knockout mice. Treatment with a specific ERK inhibitor, PD-98059, reduced E2-induced vessel relaxation in both sexes but to a lesser extent in female mice. Furthermore, PD-98059 prevented PPT-induced vessel relaxation in both sexes. Both E2 and PPT treatment activated ERK as early as 5-10 min, which was attenuated by PD-98059 in aortic tissue, cultured primary vascular smooth muscle cells (VSMCs), and endothelial cells (ECs). Aortic rings denuded of endothelium showed no differences in vessel relaxation after E2 or PPT treatment, implicating a role of ECs in the observed sex differences. Here, our results are unique to show estrogen-stimulated rapid ERα signaling mediated by ERK activation in aortic tissue, as well as VSMCs and ECs in vitro, in regulating vascular function by using side-by-side comparisons in male and ovary-intact female mice in response to E2 or PPT. NEW & NOTEWORTHY Here, we assessed the estrogen receptor-α dependency of estrogenic effects in vasorelaxation of both male and ovary-intact female mice by performing side-by-side comparisons. Also, we describe the connection between estrogen-stimulated rapid estrogen receptor-α signaling and downstream ERK activation in regulating vascular function in male and ovary-intact female mice.

Transition from Laparotomy to Laparoscopic Repair of Congenital Duodenal Obstruction in Neonates: Our Early Experience.

BACKGROUND: The aim of this report was to review our early experience of the last 7 years with repairs of congenital duodenal obstruction (CDO) to determine the efficacy and outcomes of laparoscopic repairs compared to laparotomy. METHODS: A retrospective review was conducted on all neonate (<30 days) with CDO between 2009 and 2015. Patients with duodenal atresia, stenosis, web, and annular pancreas were included. Patients with only malrotation or delayed presentation were excluded. RESULTS: Twenty-six neonates underwent laparoscopy and 30 underwent traditional laparotomy. The operative time was longer in the laparoscopic group (P = 0.001), but time to initiation of feeds and time to full feeds were similar for the laparoscopic and open groups. There was no mortality, anastomosis leakage, or stenosis in the laparoscopic group. Six laparoscopic cases required conversion to an open procedure (23%). In the earlier cases, the open conversion rate was high, but it decreased over time (P = 0.003). CONCLUSION: Laparoscopic repair is safe and effective for repair of CDO in neonates. Despite operative time was slightly longer in the laparoscopic group, clinical outcomes remained similar to the open group. For pediatric surgeon with experience in laparoscopic techniques, laparoscopic duodenoduodenostomy is a sufficient available procedure.

Incidence and management of oesophageal ruptures following fluoroscopic balloon dilatation in children with benign strictures.

OBJECTIVES: The purpose of this study is to investigate the incidence and management of oesophageal ruptures following fluoroscopic balloon dilatation (FBD) in children with benign oesophageal strictures. METHODS: Sixty-two children with benign oesophageal strictures underwent FBDs. Oesophageal rupture was categorized as intramural (type 1), transmural (type 2), or transmural with free leakage (type 3). The possible risk factors for oesophageal ruptures were analyzed. RESULTS: One hundred and twenty-nine FBDs were performed in these patients. The oesophageal rupture rate was 17.1 % (22/129). The majority (21/22) of ruptures were type 1 and type 2, both were treated conservatively. Only one patient had a type 3 rupture and underwent oesophagoesophagostomy. The patient gender, age, and the length and cause of the stricture showed no significant effect on the rupture (P > 0.05). However, for the patients ≤2 years old, the initial balloon with a diameter ≥10 mm showed a higher oesophageal rupture rate than those <10 mm during the first session (P = 0.03). CONCLUSIONS: Although the oesophageal rupture rate in children was 17.1 %, the type 3 rupture rate was 0.8 %, which usually requires aggressive treatment. For children ≤2 years old, the initial balloon diameter should be <10 mm in the first session for decreasing the risk of oesophageal rupture. KEY POINTS: • The oesophageal rupture rate following balloon dilatation in children was 17.1 %. • The incidence of transmural rupture with free leakage is very low. • Only transmural rupture with free leakage needs aggressive treatment. • For children ≤2 years, the initial balloon diameter should be <10 mm.

Hairy and enhancer of split 6 prevents hepatic lipid accumulation through inhibition of Pparg2 expression.

Peroxisome proliferator-activated receptor gamma (PPARγ) is a master regulator for white adipocyte differentiation and lipid storage. The increased level of hepatic PPARγ2 isoform reprograms liver for lipid storage and causes abnormal fat accumulation in certain pathophysiologic conditions. The current study aimed to investigate a role of transcriptional repressor hairy and enhancer of split 6 (HES6) in the regulation of Pparg2 expression and hepatic steatosis induced by diet. Liver-specific overexpression of Hes6 using adenovirus reduced Pparg2 messenger RNA levels by 90% and hepatic triglyceride accumulation by 22% compared to the levels in mice injected with an adenoviral empty vector with Western diet feeding. In sharp contrast, silencing Hes6 gene expression using short hairpin RNA increased hepatic lipid accumulation and Pparg2 messenger RNA levels by 70% and 4-fold, respectively. To locate hepatocyte nuclear factor 4 alpha (HNF4α) binding site(s), through which repressional activity of HES6 is mediated, a 2.5-kb Pparg2 promoter-driven luciferase reporter was constructed for transient transfection assays. Subsequently, chromatin immunoprecipitation and electrophoretic mobility shift assays were performed. An HNF4α binding consensus sequence was identified at 903 base pairs upstream from the transcription start site of Pparg2. Deletion or point mutation of the sequence in a luciferase reporter containing the Pparg2 promoter abolished HNF4α-mediated activation in HeLa cells. Chromatin immunoprecipitation and electrophoretic mobility shift assays further confirmed direct recruitment and binding of HNF4α to the site. Gene expression analysis with liver samples from subjects with nonalcoholic steatohepatitis suggested that the axis of the Hes6-Hnf4a-Pparg2 transcriptional cascade is also responsible for hepatic fat accumulation in humans. Conclusion: HES6 represses Pparg2 gene expression, thereby preventing hepatic lipid accumulation induced by chronic Western diet feeding or pathophysiologic conditions. (Hepatology Communications 2017;1:1085-1098).

Treatment Efficacy and Safety of Ethanol Ablation for Thyroglossal Duct Cysts: A Comparison with Surgery.

OBJECTIVE: To compare the efficacy and safety of ethanol ablation (EA) for thyroglossal duct cyst (TGDC) against surgery. METHODS: This study included 345 patients (289, surgery; 56, EA) treated for TGDC at four institutions between May 2005 and June 2014. Surgery (whole surgery and Sistrunk operation which is the current standard surgical method) and EA were compared with respect to the treatment failure and complication rates. The cost of EA and surgery was also compared. The Cox regression hazard model and linear regression were used for the adjustment of covariates. RESULTS: EA demonstrated higher treatment failures (19.6% vs. 2.4%, p < 0.001[whole surgery] and 1.2%, p = 0.004 [Sistrunk operation]), but fewer complications (1.8% vs. 10.0%, p = 0.04 [whole surgery] and 10.2%, p = 0.06 [Sistrunk operation]), and lower cost (₩423,801 vs. ₩1,435,707 [whole surgery]) than surgery. EA achieved 85.7% of treatment success up to second session. The mean volume reduction rate after EA was 82.3% at last follow-up. Young age and EA were correlated with treatment failure (p = 0.01 and 0.001, respectively). CONCLUSION: Both surgery and EA had acceptable treatment efficacy in the management of TGDC. Although there is a higher likelihood of treatment failure with EA, it has a better safety profile than surgery. KEY POINTS: • Both surgery and ethanol ablation show acceptable treatment efficacy for TGDC. • Considering treatment failure, surgery manages TGDC more effectively than EA. • EA is safer than surgery and presents no major complications. • EA could be an alternative treatment for TGDC in selected patients.