Cholestasis after Kasai operation predicts portal hypertension in native liver survivors of biliary atresia: a multicenter study.

PURPOSE: This study evaluated portal hypertension (PHT) and its predictors among native liver survivors (NLS) of biliary atresia (BA) after Kasai portoenterostomy (KPE). METHODS: This was a multicenter study using prospectively collected data. The subjects were patients who remained transplant-free for 5 years after KPE. Their status of PHT was evaluated and variables that predicted PHT were determined by regression analysis and receiver operating characteristic (ROC) curve. RESULTS: Six centers from East Asia participated in this study and 320 subjects with KPE between 1980 to 2018 were analyzed. The mean follow-up period was 10.6 ± 6.2 years. At the 5th year after KPE, PHT was found in 37.8% of the subjects (n = 121). Patients with KPE done before day 41 of life had the lowest percentage of PHT compared to operation at older age. At 12 months after KPE, PHT + ve subjects had a higher bilirubin level (27.1 ± 11.7 vs 12.3 ± 7.9 µmol/L, p = 0.000) and persistent jaundice conferred a higher risk for PHT (OR = 12.9 [9.2-15.4], p = 0.000). ROC analysis demonstrated that a bilirubin level above 38 µmol/L at 12 months after KPE predicted PHT development (sensitivity: 78%, specificity: 60%, AUROC: 0.75). CONCLUSIONS: In BA, early KPE protects against the development of PHT among NLSs. Patients with persistent cholestasis at one year after KPE are at a higher risk of this complication. They should receive a more vigilant follow-up. LEVEL OF EVIDENCE: Level III.

Analysing Factors Prolonging Hospital Stay After Excision of Choledochal Cyst-A Pathway Towards Enhanced Recovery After Surgery.

BACKGROUND: To evaluate factors affecting length of stay (LOS) after choledochal cyst resection in paediatric patients. METHODS: This was a retrospective study on patients operated between 2004 and 2021. Associations between clinical factors and LOS were evaluated by bivariate analysis, multiple regression, and equivalence test. RESULTS: Sixty-two patients were included. Twenty-four underwent hepaticoduodenostomy as biliary reconstruction. Five suffered from major complications. The median (25th-75th percentile) operation time was 279 (182-378) min. Median LOS, time to enteral feeding, and time to abdominal drain removal were 8(6-10), 2(1-3), and 5(4-7) days, respectively. Seven factors were found significantly associated with a shorter LOS in bivariate analysis and were included in multiple regression. It revealed that early abdominal drain removal (p < 0.001), early enteral feeding (p = 0.042), and the absence of major complications (p < 0.001) were significantly associated with shorter LOS. Equivalence test suggested that age and preoperative cholangitis had no practical effect on LOS. CONCLUSIONS: Early enteral feeding, early drain removal, and avoidance of major complications are associated with a shorter LOS.

The impact of pre-operative cholecystostomy on laparoscopic excision of choledochal cyst in paediatric patients.

PURPOSE: This aim of this study was to identify the pre-operative risk factors for conversion during laparoscopic excision of choledochal cyst in paediatric patients. METHODS: A retrospective single-centre study was carried out. All paediatric patients (< 18 years) who had undergone laparoscopic excision of choledochal cyst between 2004 and 2021 were reviewed. The outcome was conversion to open surgery and pre-operative factors that affected the conversion rate were analyzed. RESULTS: Sixty-one patients were included. Conversion was required in 24 cases (39.3%). There was no difference in the conversion rate between the first (before 2012, n = 30) and second (after 2012, n = 31) half of the series (36.7% vs. 42.0%, p = 0.674). Majority was type 1 cyst (86.8%) and the median cyst size was 4.6 cm (IQR: 2.2-6.4 cm). Antenatal diagnosis was available in 18 patients (29.5%). The median age at operation was 23.0 months (IQR: 8.0-72.0 months). Pre-operatively, 19 patients (31.1%) suffered from cholangitis and 5 (8.2%) of them required cholecystostomy. Comparing patients with successful laparoscopic surgery (L) and converted cases (C), there were no differences in the age at operation (p = 0.74), cyst size (p = 0.35), availability of antenatal diagnosis (p = 0.23) and cholangitic episodes (p = 0.40). However, a higher percentage of patients required cholecystostomy in the converted group (L vs. C = 2.7% vs. 16.7%, p = 0.05). Using logistic regression analysis, it was also a risk factor for conversion (OR = 3.5 [1.37-5.21], p = 0.05). CONCLUSION: Pre-operative cholecystostomy is a potential risk factor for conversion during laparoscopic excision of choledochal cyst in children.

Long-term follow-up of biliary atresia using liver transient elastography.

OBJECTIVE: Liver transient elastography (TE) using FibroScan® has gained popularity as a non-invasive technique to assess hepatic fibrosis by measuring liver stiffness. This study focused on biliary atresia patients post Kasai operation for more than 10 years to prospectively correlate the hepatic fibrosis score to the biochemical changes of liver fibrosis and clinical development of portal hypertensive complications. METHODS: TE was performed in 37 patients who had biliary atresia post Kasai operation done at median age of 60 days. Biochemical indices of liver fibrosis including aspartate aminotransferase/platelet ratio index (APRI) and Fibrosis-4 (FIB-4) score based on age, platelet count, alanine aminotransferase and aspartate aminotransferase level were calculated at the time of TE. Platelet count, spleen size, varices, ascites and hepatic encephalopathy were evaluated as clinical markers of portal hypertension. RESULTS: There were 22 female and 15 male with TE done at median age of 17.0 years. Median FibroScan® fibrosis score was 11.4. Fibrosis score of 6.8 kilopascal (kPa) was taken as the upper reference limit of normal. Nine patients (24%) had normal fibrosis score. Score above or equal to 6.8 kPa was significantly associated with lower platelet level (p = 0.001), higher INR (p = 0.043), higher APRI (p = 0.021), higher FIB-4 score (p = 0.013), and larger splenic diameter (p = 0.004). Higher FibroScan® fibrosis score was also significantly associated with portal hypertensive complications (p = 0.001). CONCLUSIONS: The FibroScan® fibrosis score correlated well with the biochemical changes of liver fibrosis and development of portal hypertensive complications clinically. Screening of portal hypertensive complications such as varices is recommended for patients with raised fibrosis score upon long-term follow-up. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

De novo mutations in Caudal Type Homeo Box transcription Factor 2 (CDX2) in patients with persistent cloaca.

The cloaca is an embryonic cavity that is divided into the urogenital sinus and rectum upon differentiation of the cloacal epithelium triggered by tissue-specific transcription factors including CDX2. Defective differentiation leads to persistent cloaca in humans (PC), a phenotype recapitulated in Cdx2 mutant mice. PC is linked to hypo/hyper-vitaminosis A. Although no gene has ever been identified, there is a strong evidence for a genetic contribution to PC. We applied whole-exome sequencing and copy-number-variants analyses to 21 PC patients and their unaffected parents. The damaging p.Cys132* and p.Arg237His de novo CDX2 variants were identified in two patients. These variants altered the expression of CYP26A1, a direct CDX2 target encoding the major retinoic acid (RA)-degrading enzyme. Other RA genes, including the RA-receptor alpha, were also mutated. Genes governing the development of cloaca-derived structures were recurrently mutated and over-represented in the basement-membrane components set (q-value < 1.65 × 10-6). Joint analysis of the patients' profile highlighted the extracellular matrix-receptor interaction pathway (MsigDBID: M7098, FDR: q-value < 7.16 × 10-9). This is the first evidence that PC is genetic, with genes involved in the RA metabolism at the lead. Given the CDX2 de novo variants and the role of RA, our observations could potentiate preventive measures. For the first time, a gene recapitulating PC in mouse models is found mutated in humans.

Short-term and long-term outcomes after Roux-en-Y hepaticojejunostomy versus hepaticoduodenostomy following laparoscopic excision of choledochal cyst in children.

BACKGROUND: Choledochal cysts are congenital dilations of the biliary tree. Complete cyst excision and biliary-enteric reconstruction have been the standard operations. In our center, more than 95% of choledochal cyst excision is now performed laparoscopically. Majority of current studies describe laparoscopic-assisted reconstruction using Roux-en-Y hepaticojejunostomy (HJ). However, only a few have studied laparoscopic hepaticoduodenostomy (HD) as an alternative method of biliary-enteric reconstruction. In this study, we focused on comparing longer-term outcomes between laparoscopic HJ and HD reconstruction following choledochal cyst excision. METHODS: We performed retrospective analysis of 54 children who had undergone laparoscopic choledochal cyst excision and biliary-enteric reconstruction between October 2004 and April 2018. Short-term outcomes including operative time, complications such as anastomotic leakage and bleeding, and hospital stays were included. Long-term outcomes including contrast reflux into biliary tree, cholangitis, anastomotic strictures, and need of reoperation were analyzed. RESULTS: Of the 54 patients, 21 of them underwent laparoscopic HD and 33 underwent laparoscopic Roux-en-Y HJ anastomosis reconstruction. There were no significant differences in gestation, gender, age at operation, antenatal diagnosis, and Todani type of choledochal cyst between HD and HJ group. Operative time was significantly shortened in HD group (p = 0.001). Median time to enteral feeding was 3 days in both groups. Median intensive care unit (p = 0.001) and hospital stay (p = 0.019) were significantly shorter in HD group. There was no perioperative mortality. There was no significant difference in anastomotic leakage requiring reoperation (p = 0.743). There were no significant differences in long-term outcomes including anastomotic stricture (p = 0.097), cholangitis (p = 0.061), symptoms of recurrent abdominal pain or gastritis (p = 0.071), or need of reoperation (p = 0.326). All patients had normal postoperative serum bilirubin level. CONCLUSIONS: Laparoscopic excision of choledochal cyst with HD reconstruction is safe and feasible with better short-term outcomes and comparable long-term outcomes compared to Roux-en-Y HJ reconstruction.

Biliary-enteric reconstruction with hepaticoduodenostomy following laparoscopic excision of choledochal cyst is associated with better postoperative outcomes: a single-centre experience.

BACKGROUND: With the advent of laparoscopic surgery, more choledochal cysts are excised laparoscopically. In this study, we compared the outcomes from laparoscopic hepaticojejunostomy (HJ) and hepaticoduodenostomy (HD) for biliary-enteric reconstruction. METHODS: A retrospective analysis of patients who had undergone laparoscopic choledochal cyst excision between February 2005 and January 2014 in a tertiary referral centre was performed. Demographics data, operative techniques and surgical outcomes were analysed according to the way of biliary-enteric reconstruction. RESULTS: A total of 31 patients were identified, 20 of whom underwent HJ and 11 underwent HD. There were no significant differences in terms of demographics. Median operative time was significantly shorter in HD group (211.0 ± 96.4 vs. 386.0 ± 90.4 min, p = 0.001). Although postoperative enteral feeding was initiated later in HD group (5.0 ± 0.8 vs. 4.0 ± 3.6 days, p = 0.036), postoperative stay in intensive care unit (ICU) (0.7 ± 1.0 vs. 2.4 ± 1.7 days, p = 0.007) and overall hospital stay (9.1 ± 1.0 vs. 14.4 ± 12.2 days, p = 0.157) favoured HD group. There was no perioperative mortality. Median follow-up duration was 24.0 (±11.0) months in HD group and 67.5 (±23.7) months in HJ group. One patient in HJ group had postoperative cholangitis related to anastomotic stricture whereas no cholangitis noted in HD group. In total, five patients in HJ group required second operation for complications and residual diseases whereas none in HD group required reoperation. CONCLUSIONS: Laparoscopic excision of choledochal cyst with hepaticoduodenostomy reconstruction is safe and feasible with shorter operative time, ICU stay and overall hospital stay. It is not inferior to HJ in terms of short-term postoperative outcomes.

Iatrogenic diaphragmatic hernia in paediatric patients.

BACKGROUND AND METHODS: Iatrogenic diaphragmatic hernia in childhood is rare, with only scanty case reports available in the literature. It is a potentially life-threatening condition resulting in intestinal obstruction and bowel strangulation. In this study, we retrospectively reviewed four patients with iatrogenic diaphragmatic hernia following right hepatic trisectionectomy with caudate lobectomy and liver transplantation in a tertiary referral centre. The patient characteristics, clinical presentation and risk factors were assessed. CONCLUSIONS: Iatrogenic diaphragmatic hernia should be considered in differential diagnosis in paediatric patients presenting with intestinal obstruction or respiratory distress after hepatic resection or liver transplantation for early diagnosis and management.

Attitudes and perceptions of influenza vaccination among Hong Kong doctors and medical students before the 2009 pandemic.

BACKGROUND: Vaccination is an important preventive measure for preparing against the influenza pandemics. This study investigated the attitudes and perceptions of influenza vaccination among doctors and medical students in Hong Kong. METHODS: A cross-sectional survey was conducted among 204 doctors and 242 medical students in a teaching hospital in 2009. Participants' demographic and job characteristics, and influenza experience and vaccination in the previous year were assessed in the questionnaire. Logistic regression models were used to examine the associations between uptake of influenza vaccination and the perceived benefits. RESULTS: Medical students were more likely to have receive an influenza vaccination in the previous year (66.9 vs. 39.7%) and acknowledged the related benefits than doctors. Moreover, uptake of influenza vaccine was associated with perceived benefits of vaccination in both doctors and medical students. CONCLUSIONS: The perceived benefits of influenza vaccination are an important factor in vaccine uptake for both doctors and medical students in Hong Kong, and should be reinforced in the professional training.

The outcome of Kasai portoenterostomy after day 70 of life.

Background: The age at Kasai portoenterostomy (KPE) was reported to correlate with the prognosis of patients with biliary atresia (BA) and that a late KPE is bounded to be failure. Herewith, we reported the outcome of patients receiving KPE after day 70 of life. In addition, the prognostic indicators were evaluated. Materials and Methods: This was a retrospective analysis and all BA patients receiving KPE after day 70 of life in a tertiary centre between 1980 and 2018 were evaluated. Results: A total of 164 KPE procedures were performed during the study period and 62 cases were done after day 70 of life which were included in this study. The median follow up period of these patients was 10.6 years (range: 4.5 to 41.5 years). Thirty-nine patients (62.9%) patients were able to achieve jaundice clearance at 6 months after KPE. The NLS rate was 53.2% (n = 33) as recorded at the time of writing. There was no statistical difference in the age at KPE between native liver survivors and patients requiring liver transplant. For complications among the native liver survivors (n = 33), portal hypertension and recurrent cholangitis were found in 63.6% and 30.3% of these patients. There was also no significant difference in the age at KPE between those who developed portal hypertension and recurrent cholangitis (p = 0.451 and p = 0.173 respectively). Regarding the prognostic indicators in predicting NLS, pre-KPE bilirubin, alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) were significantly higher among patients requiring liver transplant (p = 0.012, =0.011 and =0.017 respectively). The bilirubin level at 6 months after KPE was also higher among patients who required liver transplant (p = 0.016). Conclusion: More than half of the BA patients can survive for 10 years with their native liver despite KPE was performed after day 70 of life. However, they have a higher chance to develop BA-related complications. The level of pre-KPE bilirubin and ductal enzymes as well as post-KPE bilirubin are prognostic indicators to predict NLS.

Paediatric thyroidectomy: When and why? A 25-year institutional experience.

OBJECTIVE: Thyroidectomy in paediatric patients is relatively uncommon. In this study, we reviewed our experience of thyroidectomy in children and identified risk factors associated with postoperative complications. METHODS: We performed a retrospective analysis of paediatric patients who had thyroidectomy in our institution between April 1995 and January 2021. Demographic data, preoperative cytological findings, indications of surgery, surgical complications and histological results were analysed. RESULTS: A total of 87 paediatric patients with 92 thyroidectomy were identified. The indications for surgery were Graves' disease refractory to medical treatments (40.2%), benign thyroid nodules or multinodular goitre (26.4%), thyroid carcinoma (23.0%) and multiple endocrine neoplasm type 2A syndrome (10.3%). Patients presented with thyroid nodules or cervical lymph nodes had a 43.9% risk of malignancy. 66 total thyroidectomy were done with median operation time of 134 min(102-170), while 26 hemi-thyroidectomy were performed (Right side 12/92, Left side 14/92) with median operation time of 65 min(49-102). The median postoperative hospital stay was 2 days(1-4). Intraoperative neck dissection (p = 0.003), drain insertion (p = 0.001) and hypocalcaemia requiring medical treatment (p = 0.004) were associated with longer hospital stay. The median follow-up was 11.3 years (3.0-16.8). 32% patients had immediate postoperative hypocalcaemia and 8% patients had permanent hypoparathyroidism. Transient vocal cord palsy was found in 3 patients(3%) and all resolved within 5-month time upon reassessment direct laryngoscopy. The use of intraoperative recurrent laryngeal nerve monitoring was associated with less vocal cord palsy (p = 0.022). The median disease-free survival was 13.7 years(7.4-17.7) for patients operated for well-differentiated thyroid carcinoma(WDTC). amongst the 9 patients who had prophylactic total thyroidectomy for MEN2A syndrome, 44% were found to have medullary thyroid microcarcinomas on pathology. CONCLUSIONS: Surgical management of paediatric thyroid disease can be complex. Postoperative hypocalcaemia and vocal cord palsy were usually transient after total thyroidectomy. The use of intraoperative recurrent laryngeal nerve monitoring had resulted in less vocal cord palsy. Long-term disease-free survival of patients with thyroid cancer had been achieved with multi-disciplinary management in our centre. LEVEL OF EVIDENCE: Retrospective Comparative Study; Level III.

Peptoid atropisomers.

We report the isolation of N-aryl peptoid oligomers that adopt chiral folds, despite the absence of chiral centers. Peptoid monomers incorporating ortho-substituted N-aryl side chains are identified that exhibit axial chirality. We observe significant energy barriers to rotation about the stereogenic carbon-nitrogen bond, allowing chromatographic purification of stable atropisomeric forms. We study the atropisomerism of N-aryl peptoid oligomers by computational modeling, NMR, X-ray crystallography, dynamic HPLC, and circular dichroism. The results demonstrate a new approach to promote the conformational ordering of this important class of foldamer compounds.

Life long follow up and management strategies of patients living with native livers after Kasai portoenterostomy.

We present a 37 years' experience in the management of biliary atresia (BA) and discuss long-term complications after Kasai portoenterostomy (KPE). A retrospective territory-wide study from 1980 to 2017 on 231 patients with open KPE from three tertiary paediatric surgical centres was performed. Outcome parameters were clearance of jaundice (COJ), native liver survival (NLS) and long-term complications. Factors affecting the operative outcomes were analyzed. The median duration of follow up was 17.5 (IQR: 13.5-22) years. Over 66% of patients became jaundice-freed at 1 year after KPE. Seventy patients (30.3%) received liver transplant (LT) at a median age of 6.2 (IQR: 4.3-8.4) years. The NLS rates at 10 and 20 years were 70.7% and 61.5% respectively with no significant change over the study period. The median age at KPE was 59 (IQR: 49-67) days. KPE performed before 70 days was associated with higher odd ratios for successful drainage but the age of KPE did not have an impact on the long-term NLS. Among all native liver survivors (n = 153), the median bilirubin level was 24 (IQR: 16-36) µmol/L. Portal hypertension (PHT) and recurrent cholangitis were found in 51.6% and 27.5% of them respectively. With a vigilant follow up program, more than 60% of BA patients could remain stable with the disease and achieve long-term survival without LT. Although cholestasis, portal hypertension and recurrent cholangitis are common in long-term NLS, with a comprehensive follow management strategy, they do not always necessitate LT. Our study serves as an example for countries where deceased donor organs are scarce due to very low donation rate.

Identification of a wide spectrum of ciliary gene mutations in nonsyndromic biliary atresia patients implicates ciliary dysfunction as a novel disease mechanism.

BACKGROUND: Biliary atresia (BA) is the most common obstructive cholangiopathy in neonates, often progressing to end-stage cirrhosis. BA pathogenesis is believed to be multifactorial, but the genetic contribution, especially for nonsyndromic BA (common form: > 85%) remains poorly defined. METHODS: We conducted whole exome sequencing on 89 nonsyndromic BA trios to identify rare variants contributing to BA etiology. Functional evaluation using patients' liver biopsies, human cell and zebrafish models were performed. Clinical impact on respiratory system was assessed with clinical evaluation, nasal nitric oxide (nNO), high speed video analysis and transmission electron microscopy. FINDINGS: We detected rare, deleterious de novo or biallelic variants in liver-expressed ciliary genes in 31.5% (28/89) of the BA patients. Burden test revealed 2.6-fold (odds ratio (OR) [95% confidence intervals (CI)]= 2.58 [1.15-6.07], adjusted p = 0.034) over-representation of rare, deleterious mutations in liver-expressed ciliary gene set in patients compared to controls. Functional analyses further demonstrated absence of cilia in the BA livers with KIF3B and TTC17 mutations, and knockdown of PCNT, KIF3B and TTC17 in human control fibroblasts and cholangiocytes resulted in reduced number of cilia. Additionally, CRISPR/Cas9-engineered zebrafish knockouts of KIF3B, PCNT and TTC17 displayed reduced biliary flow. Abnormally low level of nNO was detected in 80% (8/10) of BA patients carrying deleterious ciliary mutations, implicating the intrinsic ciliary defects. INTERPRETATION: Our findings support strong genetic susceptibility for nonsyndromic BA. Ciliary gene mutations leading to cholangiocyte cilia malformation and dysfunction could be a key biological mechanism in BA pathogenesis. FUNDING: The study is supported by General Research Fund, HMRF Commissioned Paediatric Research at HKCH and Li Ka Shing Faculty of Medicine Enhanced New Staff Start-up Fund.

Cancer gene mutations in congenital pulmonary airway malformation patients.

BACKGROUND: Newborns affected with congenital pulmonary airway malformations (CPAMs) may present with severe respiratory distress or remain asymptomatic. While surgical resection is the definitive treatment for symptomatic CPAMs, prophylactic elective surgery may be recommended for asymptomatic CPAMs owing to the risk of tumour development. However, the implementation of prophylactic surgery is quite controversial on the grounds that more evidence linking CPAMs and cancer is needed. The large gap in knowledge of CPAM pathogenesis results in uncertainties and controversies in disease management. As developmental genes control postnatal cell growth and contribute to cancer development, we hypothesised that CPAMs may be underlain by germline mutations in genes governing airways development. METHODS: Sequencing of the exome of 19 patients and their unaffected parents. RESULTS: A more than expected number of mutations in cancer genes (false discovery rate q-value <5.01×10-5) was observed. The co-occurrence, in the same patient, of damaging variants in genes encoding interacting proteins is intriguing, the most striking being thyroglobulin (TG) and its receptor, megalin (LRP2). Both genes are highly relevant in lung development and cancer. CONCLUSIONS: The overall excess of mutations in cancer genes may account for the reported association of CPAMs with carcinomas and provide some evidence to argue for prophylactic surgery by some surgeons.

Peroral Endoscopic Myotomy with EndoFLIP and Double-Endoscope: Novel Techniques for Achalasia in Pediatric Population.

BACKGROUND: Experience of peroral endoscopic myotomy (POEM) for treatment of achalasia in pediatric population is limited with varying techniques in different centers. The accurate extent of submucosal tunneling into the gastric cardia and the adequacy of myotomy are the important determining factors to success of POEM. A majority of studies in pediatric population have described using submucosal dye injection for assessing the adequacy of myotomy, however, this is a rather crude and inaccurate method. We herein describe the first case of pediatric achalasia managed with POEM incorporated with novel combined techniques using EndoFLIP® (Endoluminal Functional Lumen Imaging Probe) and double endoscope. METHODS: Esophagogastric junction (EGJ) was identified with a gastroscope. Before POEM, EndoFLIP showed EGJ distensibility index of 1.7 mm2/mmHg. Submucosal tunnel was created from the mucosal entry site at midesophagus down and ∼3 cm beyond the EGJ. Anterior myotomy cutting the circular muscle layer while preserving the longitudinal muscle was performed for 8 cm. Double-endoscope technique was used to confirm the adequacy of myotomy by inserting a smaller endoscope through nostril into stomach and observing the transillumination of the first endoscope at the end of submucosal tunnel. After POEM, repeat EndoFLIP measurements revealed increased distensibility index to 6.0 mm2/mmHg. Endoscopic examination at the end of the procedure showed widely patent EGJ. RESULTS: Eckardt symptoms score improved from 9 to 0. At 7 month after POEM, esophagoscopy showed widely open EGJ with no esophagitis, and high-resolution esophageal manometry revealed normalized lower esophageal sphincter pressure and resting tone. CONCLUSIONS: We introduced the intraoperative use of EndoFLIP system that allows real-time assessment of EGJ distensibility and immediate treatment effect evaluation. Incorporation of double-endoscope POEM was also first described in our pediatric patient for ensuring complete gastric myotomy. From our experiences, POEM for achalasia in pediatric population appears to have encouraging results similar to adult patients.

Gone, But Not Forgotten? Survey of Resident Attitudes Toward a Cultural Standardized Patient Examination for a General Surgery Residency Program.

Purpose: Various tools have been utilized for cultural competency training in residency programs, including cultural standardized patient examinations. However, it is unknown whether residents feel the training they received has a long-term impact on how they care for patients. The purpose of this study was to assess whether surgical residents who participated in a cultural standardized patient examination view the experience as beneficial. Methods: Surgical residents who completed a standardized patient examination from Fall 2009 to Spring 2015 were asked to complete a 13-question survey assessing the following: (1) did participants feel prepared when dealing with patients from different cultural backgrounds, (2) did they feel the standardized patient experience was beneficial or improved their ability to care for patients, and (3) did they perceive that cultural competence was important when dealing with patients. Results: Sixty current/former residents were asked to participate and 24 (40%) completed the survey. All agreed cross-cultural skills were important and almost all reported daily interaction with patients from different cultural backgrounds. Sixteen participants (67%) reported the cultural standardized patient examination aided their ability to care for culturally dissimilar patients, and 13 (54%) said the training helped improve their communication skills with patients. Thirteen (54%) reported they would participate in another cultural standardized patient examination. Conclusion: Development of effective cultural competency training remains challenging. This study provides some preliminary results that demonstrate the potential lasting impact of cultural competency training. Participants found the skills gained from cultural standardized patient examinations helpful.

Surgical Intervention for Primary Spontaneous Pneumothorax in Pediatric Population: When and Why?

INTRODUCTION: Spontaneous pneumothorax in pediatric patients is relatively uncommon. The management strategy varies in different centers due to dearth of evidence-based pediatric guidelines. In this study, we reviewed our experience of thoracoscopic management of primary spontaneous pneumothorax (PSP) in children and identified risk factors associated with postoperative air leakage and recurrence. MATERIALS AND METHODS: We performed a retrospective analysis of pediatric patients who had PSP and underwent surgical management in our institution between April 2008 and March 2015. Demographic data, radiological findings, interventions, and surgical outcomes were analyzed. RESULTS: A total of 92 patients with 110 thoracoscopic surgery for PSP were identified. The indications for surgery were failed nonoperative management with persistent air leakage in 32.7%, recurrent ipsilateral pneumothorax in 36.4%, first contralateral pneumothorax in 14.5%, bilateral pneumothorax in 10%, and significant hemopneumothorax in 5.5%. Bulla was identified in 101 thoracoscopy (91.8%) with stapled bullectomy performed. 14.5% patients had persistent postoperative air leakage and treated with reinsertion of thoracostomy tube and chemical pleurodesis. 17.3% patients had postoperative recurrence occurred at mean time of 11 months. Operation within 7 days of symptoms onset was associated with less postoperative air leakage (P = .04). Bilateral pneumothorax and those with abnormal radiographic features had significantly more postoperative air leakage (P = .002, P < .01 respectively) and recurrence (P < .01, P = .007). CONCLUSION: Early thoracoscopic mechanical pleurodesis and stapled bullectomy after thoracostomy tube insertion could be offered as a primary option for management of large PSP in pediatric population, since most of these patients had bulla identified as the culprit of the disease.

Early Reoperations after Primary Repair of Jejunoileal Atresia in Newborns.

Aim: To review nine-year experience in managing jejuno-ileal atresia (JIA) by primary resection and anastomosis and identify factors associated with reoperations. Methods: From April 2006 to May 2015, all consecutive neonates who underwent bowel resection and primary anastomosis for JIA were analyzed retrospectively. Patients with temporary enterostomy were excluded. Patient demographics, types of atresia, surgical techniques, need for reoperations, and long-term outcomes were investigated. Results: A total of forty-three neonates were included, in which nineteen (44.2%) of them were preterm and fourteen (32.6%) were of low birth weight. Thirteen patients (30.2%) had jejunal atresia whereas thirty patients (69.8%) had ileal atresia. Volvulus, intussusception and meconium peritonitis were noted in 12, 8, and13 patients, respectively. Eight patients (18.6%) had short bowel syndrome after operation. Ten patients (23.3%) required reoperations from 18 days to 4 months after the initial surgery due to anastomotic stricture (n=1), adhesive intestinal obstruction (n=1), small bowel perforation (n=2) and functional obstruction (n=6). Prematurity and low birth weight were associated with functional obstruction leading to reoperation (p=0.04 and 0.01 respectively). The overall long-term survival was 97.7%. All surviving patients achieved enteral autonomy and catch-up growth at a median follow-up of 4.7 years. Conclusion: Long-term survival of JIA after primary resection and anastomosis are excellent. However, patients have substantial risk of early reoperations to tackle intraabdominal complications.

Genetic study of congenital bile-duct dilatation identifies de novo and inherited variants in functionally related genes.

BACKGROUND: Congenital dilatation of the bile-duct (CDD) is a rare, mostly sporadic, disorder that results in bile retention with severe associated complications. CDD affects mainly Asians. To our knowledge, no genetic study has ever been conducted. METHODS: We aim to identify genetic risk factors by a "trio-based" exome-sequencing approach, whereby 31 CDD probands and their unaffected parents were exome-sequenced. Seven-hundred controls from the local population were used to detect gene-sets significantly enriched with rare variants in CDD patients. RESULTS: Twenty-one predicted damaging de novo variants (DNVs; 4 protein truncating and 17 missense) were identified in several evolutionarily constrained genes (p < 0.01). Six genes carrying DNVs were associated with human developmental disorders involving epithelial, connective or bone morphologies (PXDN, RTEL1, ANKRD11, MAP2K1, CYLD, ACAN) and four linked with cholangio- and hepatocellular carcinomas (PIK3CA, TLN1 CYLD, MAP2K1). Importantly, CDD patients have an excess of DNVs in cancer-related genes (p < 0.025). Thirteen genes were recurrently mutated at different sites, forming compound heterozygotes or functionally related complexes within patients. CONCLUSIONS: Our data supports a strong genetic basis for CDD and show that CDD is not only genetically heterogeneous but also non-monogenic, requiring mutations in more than one genes for the disease to develop. The data is consistent with the rarity and sporadic presentation of CDD.