Single-cell transcriptomics of human cholesteatoma identifies an activin A-producing osteoclastogenic fibroblast subset inducing bone destruction.

Cholesteatoma, which potentially results from tympanic membrane retraction, is characterized by intractable local bone erosion and subsequent hearing loss and brain abscess formation. However, the pathophysiological mechanisms underlying bone destruction remain elusive. Here, we performed a single-cell RNA sequencing analysis on human cholesteatoma samples and identify a pathogenic fibroblast subset characterized by abundant expression of inhibin ßA. We demonstrate that activin A, a homodimer of inhibin ßA, promotes osteoclast differentiation. Furthermore, the deletion of inhibin ßA /activin A in these fibroblasts results in decreased osteoclast differentiation in a murine model of cholesteatoma. Moreover, follistatin, an antagonist of activin A, reduces osteoclastogenesis and resultant bone erosion in cholesteatoma. Collectively, these findings indicate that unique activin A-producing fibroblasts present in human cholesteatoma tissues are accountable for bone destruction via the induction of local osteoclastogenesis, suggesting a potential therapeutic target.

Single-cell RNA sequencing of intestinal immune cells in neonatal necrotizing enterocolitis.

PURPOSE: Necrotizing enterocolitis (NEC) causes fatal intestinal necrosis in neonates, but its etiology is unknown. We analyzed the intestinal immune response to NEC. METHODS: Using single-cell RNA sequencing (scRNA-seq), we analyzed the gene expression profiles of intestinal immune cells from four neonates with intestinal perforation (two with NEC and two without NEC). Target mononuclear cells were extracted from the lamina propria of the resected intestines. RESULTS: In all four cases, major immune cells, such as T cells (15.1-47.7%), B cells (3.1-19.0%), monocytes (16.5-31.2%), macrophages (1.6-17.4%), dendritic cells (2.4-12.2%), and natural killer cells (7.5-12.8%), were present in similar proportions to those in the neonatal cord blood. Gene set enrichment analysis showed that the MTOR, TNF-α, and MYC signaling pathways were enriched in T cells of the NEC patients, suggesting upregulated immune responses related to inflammation and cell proliferation. In addition, all four cases exhibited a bias toward cell-mediated inflammation, based on the predominance of T helper 1 cells. CONCLUSION: Intestinal immunity in NEC subjects exhibited stronger inflammatory responses compared to non-NEC subjects. Further scRNA-seq and cellular analysis may improve our understanding of the pathogenesis of NEC.

＜Editors' Choice＞ Long-term outcomes of the partial splenectomy for hypersplenism after portoenterostomy of patients with biliary atresia.

Massive splenomegaly and hypersplenism in patients with biliary atresia after Kasai portoenterostomy were treated with partial splenic embolization or total splenectomy. We performed partial splenectomy to reduce the complications of partial splenic embolization and avoid overwhelming post-splenectomy infection. This study aimed to evaluate the long-term effects of partial splenectomy for hypersplenism on postoperative liver and spleen function in patients with biliary atresia. Among jaundice-free patients with biliary atresia who underwent Kasai portoenterostomy between January 1992 and December 2012, 15 underwent partial splenectomy for massive splenomegaly and hypersplenism at our institution. Changes in the laboratory data 10 years post partial splenectomy were retrospectively investigated, and these along with the latest data were measured. A total of four patients (27%) required living-donor liver transplantation after partial splenectomy, a proportion similar to those who did not undergo partial splenectomy. Compared to the preoperative baseline, the platelet counts were significantly higher at 1 and 3 years after surgery (p < 0.05). Aspartic aminotransferase-to-platelet ratio index was significantly lower at 1, 7, and 10 years after partial splenectomy (p < 0.05). No further surgeries were required for hypersplenism after partial splenectomy over 10 years, and there were no cases of overwhelming post-splenectomy infection after partial splenectomy. Partial splenectomy is safe and effective for the treatment of hypersplenism with biliary atresia over a long time period. It could be considered as an alternative to partial splenic embolization as it can suppress hypersplenism for a long time and induces fewer postoperative complications.

Identification of novel neuroblastoma biomarkers in urine samples.

Urine is a complex liquid containing numerous small molecular metabolites. The ability to non-invasively test for cancer biomarkers in urine is especially beneficial for screening child patients. This study attempted to identify neuroblastoma biomarkers by comprehensively analysing urinary metabolite samples from children. A total of 87 urine samples were collected from 54 participants (15 children with neuroblastoma and 39 without cancer) and used to perform a comprehensive analysis. Urine metabolites were extracted using liquid chromatography/mass spectrometry and analysed by Metabolon, Inc. Biomarker candidates were extracted using the Wilcoxon rank sum test, random forest method (RF), and orthogonal partial least squares discriminant analysis (OPLS-DA). RF identified three important metabolic pathways in 15 samples from children with neuroblastoma. One metabolite was selected from each of the three identified pathways and combined to create a biomarker candidate (3-MTS, CTN, and COR) that represented each of the three pathways; using this candidate, all 15 cases were accurately distinguishable from the control group. Two cases in which known biomarkers were negative tested positive using this new biomarker. Furthermore, the predictive value did not decrease in cases with a low therapeutic effect. This approach could be effectively applied to identify biomarkers for other cancer types.

Risk factors and outcomes of bile leak after laparoscopic surgery for congenital biliary dilatation.

PURPOSE: One of the main causes of stricture at hepaticojejunostomy site after surgery for congenital biliary dilatation is inflammation or infection associated with bile leak. The aim of this study was to determine the risk factors and outcomes of bile leak after laparoscopic surgery. METHODS: We retrospectively reviewed the demographics and outcomes of patients who underwent laparoscopic surgery for congenital biliary dilatation between September 2013 and December 2019. Data from patients with bile leak were compared to data from patients without bile leak. RESULTS: Fourteen of 78 patients had bile leak. Hepatic duct diameter at anastomosis was the only risk factor of bile leak. Patients with the diameter ≤ 10 mm had higher incidence of bile leak than in patients with the diameter > 10 mm (P = 0.0023). Among them, bile leak occurred more frequently in patients operated on by non-qualified surgeons based on the Japan Society for Endoscopic Surgery endoscopic surgical skill qualification system than by qualified surgeons (P = 0.027). However, none of the patients with bile leak developed anastomotic stricture afterwards. CONCLUSION: Although good technical skill is necessary to avoid bile leak in narrow hepatic duct cases (≤ 10 mm), slight bile leak may not result in anastomotic stricture.

Progenitor Cells from the Adult Human Inner Ear.

Loss of inner ear hair cells leads to incurable balance and hearing disorders because these sensory cells do not effectively regenerate in humans. A potential starting point for therapy would be the stimulation of quiescent progenitor cells within the damaged inner ear. Inner ear progenitor/stem cells, which have been described in rodent inner ears, would be principal candidates for such an approach. Despite the identification of progenitor cell populations in the human fetal cochlea and in the adult human spiral ganglion, no proliferative cell populations with the capacity to generate hair cells have been reported in vestibular and cochlear tissues of adult humans. The present study aimed at filling this gap by isolating colony-forming progenitor cells from surgery- and autopsy-derived adult human temporal bones in order to generate inner ear cell types in vitro. Sphere-forming and mitogen-responding progenitor cells were isolated from vestibular and cochlear tissues. Clonal spheres grown from adult human utricle and cochlear duct were propagated for a limited number of generations. When differentiated in absence of mitogens, the utricle-derived spheres robustly gave rise to hair cell-like cells, as well as to cells expressing supporting cell-, neuron-, and glial markers, indicating that the adult human utricle harbors multipotent progenitor cells. Spheres derived from the adult human cochlear duct did not give rise to hair cell-like or neuronal cell types, which is an indication that human cochlear cells have limited proliferative potential but lack the ability to differentiate into major inner ear cell types. Anat Rec, 303:461-470, 2020. © 2019 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.

Laparoscopic Kasai portoenterostomy is advantageous over open Kasai portoenterostomy in subsequent liver transplantation.

BACKGROUND: Native liver survival after laparoscopic Kasai portoenterostomy (Lap-PE) for biliary atresia (BA) is controversial. We examined whether a jaundice-free native liver survival rate is comparable between conventional Kasai portoenterostomy (Open-PE) and Lap-PE. Then, the impact of the two types of PE on subsequent living-donor liver transplantation (LTx) was addressed in this study. METHODS: The jaundice-free rate in 1- and 2-year-old patients who underwent Open-PE and Lap-PE from January 2006 to December 2017 was investigated. Additionally, perioperative data (duration from the start of surgery to the completion of hepatectomy and others) of patients aged 2 years or younger who underwent LTx after either Open-PE or Lap-PE from 2006 to 2017 were evaluated. RESULTS: Thirty-one (67%) out of 46 Open-PE patients and 23 (77%) out of 30 Lap-PE patients showed native liver survival with jaundice-free status at 1 year of age (p = 0.384); 29 (63%) out of 46 Open-PE patients and 19 (70%) out of 27 Lap-PE patients showed native liver survival with jaundice-free status at 2 years of age (p = 0.524); there were no significant differences. Additionally, there were 37 LTx cases after PE within 2 years of birth, including 29 Open-PE and 8 Lap-PE cases. The patients in the Lap-PE group had fewer adhesions and significantly shorter durations of surgery up to the completion of the recipient's hepatectomy and durations of post-LTx hospital stay compared to the Open-PE group. There were no differences in blood loss or duration of stay in intensive care unit between the Lap-PE and Open-PE groups. CONCLUSIONS: Jaundice-free native liver survival rate has been comparable between Open-PE and Lap-PE. Lap-PE resulted in fewer adhesions, contributing to better outcomes of subsequent LTx compared to Open-PE.

Clinical significance of cervical and ocular vestibular evoked myogenic potentials in benign paroxysmal positional vertigo: a meta-analysis.

PURPOSE: As the pathological cause of benign paroxysmal positional vertigo (BPPV), the dislocation or degeneration of otoconia in the utricle and saccule is suggested. Vestibular evoked myogenic potential (VEMP) could reflect otolithic dysfunction due to these etiologies of BPPV. The aim of this study was to validate the clinical significance of cervical (c) and ocular (o) VEMP in BPPV by a meta-analysis of previous articles. METHODS: Articles related to BPPV with data on cVEMP and oVEMP were collected. The following keywords were used to search PubMed and Scopus for English language articles: benign paroxysmal positional vertigo or BPPV and vestibular evoked myogenic potential or VEMP. RESULTS: The p13 latency in cVEMP and n1 latency in oVEMP were slightly but significantly prolonged in BPPV patients compared to control patients. AR in oVEMP of BPPV patients also showed higher value than that of control patients. However, the n23 latency and AR in cVEMP and p1 latency in oVEMP showed no significant difference between BPPV and control patients. Furthermore, latencies in VEMPs also showed no significant difference between an affected and a non-affected ear in BPPV patients. CONCLUSIONS: Our results indicated that otolith dysfunction of BPPVs was detected by latencies in VEMPs, and AR in oVEMP more sensitively reflects the difference between affected and non-affected ears in BPPV patients. The otolith dysfunction of BPPV might be induced by the systemic condition. However, the differences of latencies between BPPV patients and control patients were too small to use VEMPs as a prognostic predictor.

Efficacy of and prognosis after steroid pulse therapy in patients with poor reduction of jaundice after laparoscopic Kasai portoenterostomy.

PURPOSE: High-dose postoperative steroid therapy after Kasai portoenterostomy is reported to improve jaundice clearance and a strong anti-inflammatory activity might prevent fibrous tissue formation which is often observed at the porta hepatis in revision surgery. We started steroid pulse therapy for the patients with cessation of decrease in jaundice and aimed to evaluate the efficacy in this study. METHODS: The demographics and outcomes of patients who underwent laparoscopic Kasai portoenterostomy and received steroid pulse therapy within 2 months postoperatively between September 2014 and December 2018 were retrospectively reviewed; the therapy was determined successful when the serum total bilirubin level decreased to or below two-thirds of the pre-therapy level after 2 weeks. Patient data in the successful group were compared with those in the unsuccessful group. RESULTS: Steroid pulse therapy was successful in seven of 16 patients (43.8%). The percentage of patients whose serum total bilirubin level decreased to normal was significantly higher in the successful group at 3 months (85.7% vs. 11.1%, P = 0.0028) and after all (100% vs. 33.3%, P = 0.011). CONCLUSIONS: Steroid pulse therapy was effective for some patients. Unsuccessful cases may have little chances of jaundice clearance; revision Kasai portoenterostomy would be a good option.

Therapeutic strategy for thoracoscopic repair of esophageal atresia and its outcome.

PURPOSE: Thoracoscopic repair can be safely performed in most types of congenital esophageal atresia (EA), including in patients with long gap EA or very low birth weight. Accordingly, we performed single- or multistage thoracoscopic repair for various EA types. We aimed to report our therapeutic strategy for thoracoscopic radical surgery for treating EA and its outcome. METHODS: Outcomes of radical surgeries for treating congenital EA at our institute from 2013 to 2018 were retrospectively evaluated. RESULTS: Thirty-eight radical surgeries were evaluated: 3 Gross type-A, 1 type-B, 30 type-C, 1 type-D, and 3 type-E. The cervical approach was performed in 5 cases and thoracoscopic esophageal anastomosis in 33, including 26 single-stage (all type-C) and 7 multistage surgeries (3 type-A, 3 type-C, and 1 type-D). There were no cases of thoracotomies or intraoperative thoracoscopic surgery complications. Three cases of minor leakage were conservatively resolved. Three postoperative chylothorax surgeries (9%) and seven balloon dilatations (21%) for anastomotic stenosis were performed. CONCLUSION: Thoracoscopic radical surgery for treating EA, including single- and multistage procedures, can be performed, except in type-E cases or when the end of the proximal esophagus is located higher than the clavicle.

Osteoclasts Modulate Bone Erosion in Cholesteatoma via RANKL Signaling.

Cholesteatoma starts as a retraction of the tympanic membrane and expands into the middle ear, eroding the surrounding bone and causing hearing loss and other serious complications such as brain abscess and meningitis. Currently, the only effective treatment is complete surgical removal, but the recurrence rate is relatively high. In rheumatoid arthritis (RA), osteoclasts are known to be responsible for bone erosion and undergo differentiation and activation by receptor activator of NF-κB ligand (RANKL), which is secreted by synovial fibroblasts, T cells, and B cells. On the other hand, the mechanism of bone erosion in cholesteatoma is still controversial. In this study, we found that a significantly larger number of osteoclasts were observed on the eroded bone adjacent to cholesteatomas than in unaffected areas, and that fibroblasts in the cholesteatoma perimatrix expressed RANKL. We also investigated upstream transcription factors of RANKL using RNA sequencing results obtained via Ingenuity Pathways Analysis, a tool that identifies relevant targets in molecular biology systems. The concentrations of four candidate factors, namely interleukin-1ß, interleukin-6, tumor necrosis factor α, and prostaglandin E2, were increased in cholesteatomas compared with normal skin. Furthermore, interleukin-1ß was expressed in infiltrating inflammatory cells in the cholesteatoma perimatrix. This is the first report demonstrating that a larger-than-normal number of osteoclasts are present in cholesteatoma, and that the disease involves upregulation of factors related to osteoclast activation. Our study elucidates the molecular basis underlying bone erosion in cholesteatoma.

Effects of cochlear implants on otolith function as evaluated by vestibulo-ocular reflex and vestibular evoked myogenic potentials.

OBJECTIVE: The aim of this study was to investigate whether the insertion of an implant into the cochlea is accompanied by a deterioration in otolith function. Cervical and ocular vestibular evoked myogenic potentials (cVEMP and oVEMP) and linear vestibulo-ocular reflex (lVOR) during eccentric rotation were assessed before and after cochlear implantation (CI) to evaluate otolith function. METHODS: Twelve patients with bilateral severe sensorineural hearing loss who had undergone CI surgery in our hospital between May 2016 and November 2017 were included in this study. cVEMP and oVEMP were assessed using the asymmetry ratio (AR), calculated with the following formula: [(peak-to-peak amplitude calculated as the sum of the p13 and n23 amplitudes in the non-operated side) - (that in the operated side)]/[(that in the non-operated side) + (that in the operated side)]. The ratio of VOR gain during eccentric rotation against VOR gain during center rotation was used to assess lVOR. For eccentric rotation, patients were rotated while displaced from the axis of rotation. At the same time, linear acceleration stimulated the utricle and induced lVOR. All patients underwent cVEMP and oVEMP tests and center and eccentric rotation tests before and about 30days after CI surgery. RESULTS: Three patients with absent cVEMP responses before surgery were excluded, leaving pre-surgery cVEMP results for 9/12 patients. In five of these patients, the AR of cVEMP increased after CI, indicating that saccular function, as evaluated by cVEMP, did not deteriorate significantly postoperatively. One patient with an absent oVEMP response before CI was excluded, leaving pre-surgery oVEMP results for 11/12 patients. In 10 of these patients, the AR of oVEMP increased after CI surgery, indicating that utricular function, as evaluated by oVEMP, deteriorated significantly postoperatively. However, because the ratio of VOR gain during eccentric rotation against VOR gain during center rotation did not become worse after CI, utricular function, as evaluated by lVOR, did not deteriorate significantly postoperatively. Symptoms of vertigo became worse after CI in two of the 12 patients. CONCLUSION: CI does not cause a deterioration in saccular function, as evaluated by cVEMP. Although CI does cause a deterioration in utricular function in oVEMP tests, this is not consistent in lVOR tests. These results indicate that CI causes a slight deterioration in utricular function that is insufficient to cause vertigo or deterioration of lVOR.

A Novel Laparoscopic Surgery Model with a Device to Expand the Abdominal Working Space in Rats: The Influence of Pneumoperitoneum and Skin Incision Length on Postoperative Inflammatory Cytokines.

PURPOSE: Experimental models of laparoscopic surgery generally use large animals owing to a sufficient abdominal working space. We developed a novel laparoscopic surgery model in rats. We performed intestinal anastomosis to demonstrate the feasibility and reliability of this model. MATERIALS AND METHODS: We designed a device for rats that expanded the abdominal working space and allowed us to manipulate the intraperitoneal organs by hand under direct vision with pneumoperitoneum. We performed small bowel resection and intestinal anastomosis in rats using this model. To elucidate the effects of pneumoperitoneum and skin incision length, rats were randomly divided into four groups with differing surgical techniques: small incision group, large incision group, small incision + pneumoperitoneum group, and large incision + pneumoperitoneum group. Intraoperative abdominal pressure and postoperative cytokines were measured. RESULTS: One experimenter completed small bowel resection and hand-sewn anastomosis under direct vision without any difficulties or assistance. Carbon dioxide pneumoperitoneum was maintained at 8-10 mmHg during surgery in both pneumoperitoneum groups. Necropsies revealed no evidence of anastomotic leakage at 24 h after surgery. The interleukin-6 and C-reactive protein concentrations were significantly greater in large incision group than in small incision group, but were not significantly different between small incision + pneumoperitoneum group and small incision group. These cytokines concentrations were the greatest in large incision + pneumoperitoneum group. CONCLUSIONS: Our laparoscopic surgery model in rats is a simple and reliable experimental model. The length of skin incision might be a more influential determinant of surgical invasiveness than pneumoperitoneum.

Investigation of the feasibility and safety of single-stage anorectoplasty in neonates with anovestibular fistula.

PURPOSE: Anovestibular fistula (AVF) is the most common type of anorectal malformation in females. Delayed anorectoplasty with fistula dilatation is commonly performed during infancy; however, we have been actively performing anorectoplasty in neonates. We report the surgical complications and postoperative defecation function associated with single-stage anorectoplasty performed in neonates. METHODS: Patients who underwent surgery for AVF between 2007 and 2017 at two institutions were retrospectively studied. The operation time, amount of bleeding, time to start oral intake, perioperative complications, and Kelly's score were compared among patients who underwent surgery as neonates and those who underwent surgery as infants. RESULTS: Eighteen neonates and 17 infants underwent anterior sagittal anorectoplasty. The median operation time and time to start oral intake were significantly shorter in the neonatal group (72 min; 3 days, respectively) than in the infant group (110 min, p = 0.0002; 5 days, p = 0.0024, respectively). Postoperative wound disruption was significantly more frequent in the infant group. Of the ten patients each in the neonatal and infant groups, there was no significant difference in Kelly's score at age ≥ 4 years. CONCLUSION: Single-stage anorectoplasty in neonates with AVF can be feasibly performed and does not impair postoperative defecation function. LEVELS OF EVIDENCE: III.

Introduction of resection of intrahepatic bile duct stenosis-causing membrane or septum into laparoscopic choledochal cyst excision.

PURPOSE: We previously showed that meticulous probing and resection of the intrahepatic bile duct stenosis (IHBDS)-causing membrane or septum was effective in preventing hepatolithiasis after choledochal cyst excisions in open surgeries. Then, we introduced this maneuver into laparoscopic choledochal cyst excisions in 2014 and performed routine resections since then. The aim of this study was to show the feasibility of this method in laparoscopic surgery. METHODS: We retrospectively reviewed the demographics and outcomes of patients who underwent laparoscopic choledochal cyst excisions at our hospital between January 2014 and December 2017. The patients who underwent surgical treatment for IHBDS-causing membrane or septum were compared with those who did not undergo the procedure. The outcomes of the patients with IHBDS were also compared between patients who were ≥ 3 years of age and those < 3 years at operation. RESULTS: Seventeen of 35 patients underwent laparoscopic resection of IHBDS-causing membrane or septum. There were no complications related to the procedure although the operative time and intraoperative bleeding amount increased in the patients with IHBDS who were ≥ 3 years of age. CONCLUSIONS: Meticulous probing and excision of the IHBDS-causing membrane or septum is safe and feasible during laparoscopic choledochal cyst excision.

Single-stage laparoscopic transanal pull-through modified Swenson procedure without leaving a muscular cuff for short- and long-type Hirschsprung disease: a comparative study.

PURPOSE: The Soave procedure (SO) is performed most commonly for Hirschsprung disease. SO reduces the risk of injury to the pelvic structures; however, a residual aganglionic muscle cuff could interfere with bowel movement and lead to obstructive enterocolitis. The Swenson procedure is considered ideal in terms of peristalsis. Currently, laparoscopic surgery provides better visualization and facilitates precise dissection, possibly leading to feasible performance of the laparoscopic modified Swenson procedure (SW). We present our operative technique and the efficacy of the SW compared with that of SO. METHODS: We retrospectively reviewed the records of 16 and 27 patients who underwent SW and SO, respectively, between 2012 and 2017. RESULTS: Operative time, blood loss, length of stay, and frequency of bowel movements showed no significant difference between the two groups. In the SW group, temporary dysuria occurred in one patient, postoperative enterocolitis in two, wound infection in one, and severe perianal excoriation in four, whereas in the SO group, obstructive symptoms occurred in three patients, small-bowel obstruction in one, and severe perianal excoriation in three. The complications and outcomes were comparable between both groups. CONCLUSION: Laparoscopic SW was safe and feasible for the short-term follow-up outcomes.

Long-term outcomes and complications after laparoscopic-assisted anorectoplasty vs. posterior sagittal anorectoplasty for high- and intermediate-type anorectal malformation.

PURPOSE: Laparoscopic-assisted anorectoplasty (LAARP) is a minimally invasive procedure in which the levator ani muscle is left to potentially improve postoperative fecal continence. This study aimed to retrospectively evaluate postoperative complications and long-term outcomes of fecal continence after LAARP and compare them to those after posterior sagittal anorectoplasty (PSARP). METHODS: Forty-five male patients with high and intermediate anorectal malformation (aged ≥ 4 years) who underwent LAARP or PSARP (LAARP 29, PSARP 16) from 1999 to 2013 were included. Postoperative complications and postoperative fecal continence were retrospectively evaluated and compared. Postoperative complications were also compared before and after introducing a urethroscope during fistula resection. RESULTS: Complications after LAARP and PSARP were seen in 12 vs. 2 cases (p = 0.09) of mucosal prolapse and in 9 vs. 1 case (p = 0.07) of posterior urethral diverticulum (PUD), respectively. The incidence of PUD decreased after introduction of a urethroscopy from 40% in 8/20 cases to 11% in 1/9 cases. No significant difference was found in terms of fecal continence in both groups. CONCLUSION: Through our study, greater improvement of postoperative fecal continence after LAARP has not been shown. LAARP was at higher risk for mucosal prolapse and PUD. However, precise dissection of the urethral fistula could be performed after the introduction of urethroscopy.

Oral administration of eicosapentaenoic acid suppresses liver fibrosis in postoperative patients with biliary atresia.

PURPOSE: Biliary atresia (BA) is characterized by progressive inflammation of the biliary system. This inflammation persists and causes liver fibrosis, although jaundice disappears after Kasai portoenterostomy (KP). We aimed to confirm whether the oral administration of eicosapentaenoic acid (EPA) suppresses liver fibrosis in postoperative patients with BA. METHODS: We reviewed patients who underwent laparoscopic KP (lapKP) between January 2014 and September 2017. From December 2016, 30 mg/kg/day of EPA was orally administered to patients who opted to take medicine (EPA group). Patients who did not receive EPA were assigned to the non-EPA group. Mac-2 binding protein sugar chain modified isomer (M2BPGi) and hyaluronic acid (HA) levels were compared between the two groups in patients showing disappearance of jaundice at 6 months after the first lapKP. RESULTS: Seventeen patients in the non-EPA group and 11 in the EPA group were enrolled. At 6 months after the first lapKP, 10 patients in the non-EPA group and six in the EPA group were without jaundice. M2BPGi and HA levels were significantly lower in the EPA group. CONCLUSIONS: Liver fibrosis was suppressed in patients without jaundice 6 months after lapKP, who were administered EPA. We believe that periductular inflammation was alleviated by EPA supplementation.

Usefulness of fetal magnetic resonance imaging for postnatal management of congenital lung cysts: prediction of probability for emergency surgery.

BACKGROUND: Emergency rescue lung resection is rarely performed to treat congenital lung cysts (CLCs) in neonates. Many reports have described fetal CLC treatment; however, prenatal predictors for postnatal respiratory failure have not been characterized. We hypothesized that fetal imaging findings are useful predictors of emergency surgery. METHODS: We retrospectively studied patients with CLC who underwent lung surgery during the neonatal period in our hospital between January 2001 and December 2015. The demographic data, fetal imaging findings, and intra- and postoperative courses of patients who underwent emergency surgery (Em group) were compared with those of patients who received elective surgery, i.e., non-emergency surgery (Ne group). RESULTS: The Em group and Ne group included 7 and 11 patients, respectively. No significant difference was noted in gestational age, time at prenatal diagnosis, birth weight, and body weight at surgery. The volumes of contralateral lung per thoracic volume were significantly smaller in the Em group than in the Ne group (p = 0.0188). Mediastinal compression was more common in the Em group (7/7) than in the Ne group (4/11) (p = 0.0128). CONCLUSIONS: This is the report describing neonatal emergency lobectomy in patients with CLC evaluated by fetal MRI using the lung volume ratio and mediastinal shift. In patients with CLC, mediastinal shift and significant decreases in contralateral lung volumes during the fetal stages are good prenatal predictors of postnatal emergency lung resection.

Novel thoracoscopic navigation surgery for neonatal chylothorax using indocyanine-green fluorescent lymphography.

BACKGROUND: Postoperative chylothorax after surgery for esophageal atresia/tracheoesophageal fistula (TEF) is a rare but serious complication, especially in neonates. This study aimed to identify the thoracic duct and ligate chylous leakage sites, using thoracoscopic navigation of an indocyanine-green (ICG)-based near-infrared (NIR) fluorescence imaging system. METHODS: From November 2014 to April 2017, thoracoscopic intraoperative ICG-NIR imaging was performed in 10 newborns (11 surgeries) with first TEF operation or with persistent postoperative chylothorax after TEF operation. NIR imaging was performed 1h after an inter-toe injection of ICG. Thoracoscopic ligations against the NIR-detected leakage sites were performed with sutures. RESULTS: The thoracic duct or lymphatic leakage was directly visualized in each patient. In 8 surgeries with first thoracoscopic TEF operation, one case had suspected minor chylous leakage without postoperative chylothorax. Another case with no chylous leakage at the first operation resulted in chylothorax at postoperative day 11. In three neonates with postoperative chylothorax, leakage points were detected near the ablation site of the azygos vein during the first operation. These points were properly ligated, and postoperative chylous leakage ceased with no adverse events. CONCLUSIONS: Thoracoscopic ICG-NIR imaging encourages the repair of refractory chylothorax and seems reliable. LEVEL OF EVIDENCE: IV.