Prophylactic anti-reflux procedure for children undergoing laparoscopic gastrostomy: Rethinking of the routine practice.

AIM: Laparoscopic gastrostomy is a frequently performed procedure in children requiring long-term enteral nutrition. The role of prophylactic anti-reflux surgery during gastrostomy placements is controversial. The current study aims to evaluate the role of prophylactic anti-reflux procedures during gastrostomy placement. METHODS: A retrospective single-center analysis of all children without reflux receiving laparoscopic gastrostomy from January 2005 through December 2021 was performed. Demographics and clinical outcomes were compared between patients receiving gastrostomy placement alone and patients receiving gastrostomy with prophylactic anti-reflux surgery. RESULTS: A total of 79 patients had a confirmed absence of reflux by a 24-h pH/impedance study before operation. Thirty-six of these patients underwent prophylactic anti-reflux surgery (PAR) while 43 received gastrostomy (PG) alone. The operative time and conversion rate were significantly higher in the PAR group (140.5 ± 67.5 vs. 80.2 ± 66.8 min, p = 0.0001 and 8.3% vs. 0%, p = 0.04). There were no major complications in either group. De novo reflux was detected in five patients (11.6%) in the PG group. None of these patients progressed to require anti-reflux surgery. CONCLUSION: The occurrence of de novo reflux after laparoscopic gastrostomy was low and could be managed without anti-reflux surgery. A routine pre-operative pH study is helpful for appropriate patient selection to avoid unnecessary anti-reflux surgery, which lengthens operative time and increases the conversion rate.

Actionable pharmacogenetic variants in Hong Kong Chinese exome sequencing data and projected prescription impact in the Hong Kong population.

Preemptive pharmacogenetic testing has the potential to improve drug dosing by providing point-of-care patient genotype information. Nonetheless, its implementation in the Chinese population is limited by the lack of population-wide data. In this study, secondary analysis of exome sequencing data was conducted to study pharmacogenomics in 1116 Hong Kong Chinese. We aimed to identify the spectrum of actionable pharmacogenetic variants and rare, predicted deleterious variants that are potentially actionable in Hong Kong Chinese, and to estimate the proportion of dispensed drugs that may potentially benefit from genotype-guided prescription. The projected preemptive pharmacogenetic testing prescription impact was evaluated based on the patient prescription data of the public healthcare system in 2019, serving 7.5 million people. Twenty-nine actionable pharmacogenetic variants/ alleles were identified in our cohort. Nearly all (99.6%) subjects carried at least one actionable pharmacogenetic variant, whereas 93.5% of subjects harbored at least one rare deleterious pharmacogenetic variant. Based on the prescription data in 2019, 13.4% of the Hong Kong population was prescribed with drugs with pharmacogenetic clinical practice guideline recommendations. The total expenditure on actionable drugs was 33,520,000 USD, and it was estimated that 8,219,000 USD (24.5%) worth of drugs were prescribed to patients with an implicated actionable phenotype. Secondary use of exome sequencing data for pharmacogenetic analysis is feasible, and preemptive pharmacogenetic testing has the potential to support prescription decisions in the Hong Kong Chinese population.

Comparison and clinical analysis of antibiotics and endoscopic injection for vesicoureteral reflux in children.

PURPOSE: This study evaluated the outcome of pediatric patients with primary vesicoureteral reflux (VUR) and compared of the treatments between continued antibiotic prophylaxis (CAP) and endoscopic injection. METHODS: The clinical data of children diagnosed with primary vesicoureteral reflux from March 2015 to June 2020 who were treated with antibiotics or endoscopic injection were reviewed. Antibiotic was the first-chosen treatment after the diagnosis of VUR in children. Endoscopic treatment consisted of injection of dextran hyaluronic acid copolymer (DX/HA) into the ureteral opening under direct cystoscopy guidance. RESULTS: Fifty-two children (35 males, 17 females) were included in this study, and for a total 90 ureters (14 unilateral, 38 bilateral) were diagnosed with vesicoureteral reflux by Voiding cystourethrography (VCUG). Twenty-two children were treated with antibiotics (8 unilateral, 14 bilateral), for a total of 36 ureters; thirty children were treated by endoscopic injection (6 unilateral, 24 bilateral), for a total of 54 ureters. The injection surgery took 36 ± 17 min including duration of general anesthesia and circumcision and the hospital stay was 2.3 ± 1.3 days. All male patients underwent circumcision simultaneously. There were no drug and allergic reactions in the antibiotic group, and no postoperative complications occurred in the injection group. With 23 months (13-63 months) of mean follow-up, the resolution rate, defined as radiological disappearance of VUR, was 36.1% (13/36) in the antibiotic group and 57.4% (31/54) in the injection group (P = 0.048).Two cases of bilateral reflux in the injection group required a second injection before resolution could be achieved. Thus, the overall success rate of injection was 64.8% (35/54). 9 cases (9/18, 50%) in the antibiotic group had renal scars on DMSA scans, while this was seen in 20 cases (20/23, 86.9%) in the injection group. There was a statistically significant difference between the two groups (P = 0.010).The positive rates of ultrasound between the antibiotic group and the injection group were 45.5% (10/22) and 80.0% (24/30), respectively. There was a statistically significant difference between the two groups in positive rates of ultrasound (P = 0.010). CONCLUSIONS: Endoscopic injection is easy to operate with short surgical time and hospital stay, so it is a safe and feasible treatment. For the treatment of primary vesicoureteral reflux in children, the radiological resolution rate of endoscopic injection is better than antibiotic therapy. In this study, the presence of kidney scars on DMSA and the dilated of the collecting system on ultrasound are the indications for endoscopic injection.

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.

Management of acute intra-abdominal hemorrhage in ruptured hepatoblastoma with transarterial embolization using calibrated gelfoam particles.

This brief report aims to evaluate the treatment outcome of transarterial embolization in ruptured hepatoblastoma complicated with acute intra-abdominal hemorrhage. Three children (mean age 6 years) with high-risk hepatoblastoma presented with rupture and acute intra-abdominal hemorrhage. In addition to aggressive fluid resuscitation and blood product support, super-selective embolization of the arteries with active bleeding or pseudoaneurysm was performed using calibrated gelfoam particles, with a technical success rate of 100%. Hemodynamic status and hemoglobin level were normalized in all patients within 2 days postembolization. The 30-day survival rate was 100%. No major complication was detected apart from mild elevation of alanine transaminase.

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.

Genetics of Hirschsprung's disease.

Hirschsprung's disease (HSCR) is a classical model of enteric neuropathy, occurring in approximately 2-2.8 in 10,000 newborns. It is the commonest form of congenital bowel obstruction and is characterized by the absence of enteric ganglia in distal colon. Recent advances in genome-wide association analysis (GWAS) and next generation sequencing (NGS) studies have led to the discovery of a number of new HSCR candidate genes, thereby providing new insights into the genetic architecture and molecular mechanisms of the disease. Altogether, these findings indicated that genetic heterogeneity, variable penetrance and expressivity, and genetic interaction are the pervasive characteristics of HSCR genetics. In this review, we will provide an update on the genetic landscape of HSCR and discuss how the common and rare variants may act together to modulate the phenotypic manifestation. Translating the genetic findings to genetic risk prediction and to optimize clinical outcomes are undoubtedly the ultimate goals for genetic studies on HSCR. From this perspective, we will further discuss the major obstacles in the clinical translation of these latest genetic findings. Lastly, new measures to address these clinical challenges are suggested to advance precision medicine and to develop novel alternative therapies.

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.

Primary anastomosis is the preferred surgical approach for proximal intestinal atresia: a retrospective 20-year analysis.

PURPOSE: We aimed to compare the outcomes of primary anastomosis (PA) and enterostomy as treatments for intestinal atresia in neonates to identify the factors influencing the choice of modality. METHODS: We conducted a retrospective single-centre analysis of all neonates with intestinal atresia between 2000 and 2020 and measured the clinical outcomes. We performed logistic regression to identify factors that influenced the choice of surgical approach. RESULTS: Of 62 intestinal atresia neonates, 71% received PA. There were no significant differences in gestation, gender, age at operation, birth weight, or body weight at operation between the PA and enterostomy groups. PA reoperation was not required for 78% of patients, and the PA group had shorter hospital stays. Complications, operative time, duration on parenteral nutrition, time to full enteral feeding were comparable in both groups. Upon multivariate regression analysis, surgeons favoured PA in proximal atresia [Odds ratio (OR) 38.5, 95% Confidence Interval (CI) 2.558-579] while enterostomy in smaller body size [OR 2.75, CI 0.538-14.02] and lower Apgar score [OR 1.1, CI 0.07-17.8]. Subgroup analysis in these patient groups demonstrated comparable outcomes with both surgical approaches. CONCLUSION: Both surgical approaches achieved comparable outcomes, but PA was associated with short hospital stays and the avoidance of stoma-related complications, and reoperation was generally not required. This surgical approach was suitable for patients with proximal atresia, but enterostomy remained a sensible choice for patients with smaller body sizes and lower Apgar scores.

Developing Biliary Atresia-like Model by Treating Human Liver Organoids with Polyinosinic:Polycytidylic Acid (Poly (I:C)).

Background: We explored the feasibility of creating BA-like organoids by treating human liver organoids with Polyinosinic:Polycytidylic acid (Poly I:C). Methods: Organoids were developed from the liver parenchyma collected during Kasai portoenterostomy (BA) and surgery for other liver disorders (non-BA). The non-BA organoids were co-cultured with poly I:C (40 µg/mL). The organoid morphology from both samples was compared on day 17. RNA-sequencing was performed to examine the transcriptomic differences. Results: Non-BA liver organoids developed into well-expanded spherical organoids with a single-cell layer of epithelial cells and a single vacuole inside. After poly I:C treatment, the majority of these organoids developed into an aberrant morphology with a high index of similarity to BA organoids which are multi-vacuoled and/or unexpanded. RNA-sequencing analysis revealed that 19 inflammatory genes were commonly expressed in both groups. Conditional cluster analysis revealed several genes (SOCS6, SOCS6.1, ARAF, CAMK2G, GNA1C, ITGA2, PRKACA, PTEN) that are involved in immune-mediated signaling pathway had a distinct pattern of expression in the poly I:C treated organoids. This resembled the expression pattern in BA organoids (p < 0.05). Conclusions: Poly I:C treated human liver organoids exhibit morphology and genetic signature highly compatible to organoids developed from BA liver samples. They are potential research materials to study immune-mediated inflammation in BA.

Current Understanding in the Clinical Characteristics and Molecular Mechanisms in Different Subtypes of Biliary Atresia.

Biliary atresia is a severe obliterative cholangiopathy in early infancy that is by far the most common cause of surgical jaundice and the most common indicator for liver transplantation in children. With the advanced knowledge gained from different clinical trials and the development of research models, a more precise clinical classification of BA (i.e., isolated BA (IBA), cystic BA (CBA), syndromic BA (SBA), and cytomegalovirus-associated BA (CMVBA)) is proposed. Different BA subtypes have similar yet distinguishable clinical manifestations. The clinical and etiological heterogeneity leads to dramatically different prognoses; hence, treatment needs to be specific. In this study, we reviewed the clinical characteristics of different BA subtypes and revealed the molecular mechanisms of their developmental contributors. We aimed to highlight the differences among these various subtypes of BA which ultimately contribute to the development of a specific management protocol for each subtype.

Actionable secondary findings in 1116 Hong Kong Chinese based on exome sequencing data.

The use of exome and genome sequencing has increased rapidly nowadays. After primary analysis, further analysis can be performed to identify secondary findings that offer medical benefit for patient care. Multiple studies have been performed to evaluate secondary findings in different ethnicities. However, relevant data are limited in Chinese. Here, with the use of a cohort consisted of 1116 Hong Kong Chinese exome sequencing data, we evaluated the secondary findings in the 59 genes recommended by the American College of Medical Genetics and Genomics. Fifteen unique pathogenic or likely pathogenic variants in 17 individuals were identified, representing a frequency of 1.52% in our cohort. Although 20 individuals harboured pathogenic or likely pathogenic variants in recessive conditions, none carried bi-allelic mutations in the same gene. Our finding was in accordance with the estimation from the American College of Medical Genetics and Genomics that about 1% individuals harbour secondary findings.

Online teaching of basic surgical skills to medical students during the COVID-19 pandemic: a case-control study.

PURPOSE: Medical education has been disrupted by the COVID-19 pandemic in many countries, with face-to-face lectures replaced by pre-recorded videos. However, surgical skills training cannot be replaced easily by videos, as a high level of tutor-student interaction is required. Thus, we developed a new web-based surgical skill learning session (WSSL). This case-control study evaluates the surgical skills competency of medical students taught by the WSSL. METHODS: This case-control study compares WSSL with face-to-face tutorials. Students were assigned randomly to one of two groups according to the teaching method. Independent blinded assessment was performed by a standardized marking scheme, modified from the Objective Structured Assessment of Technical Skills (OSATS) global rating scale. RESULTS: We recruited 62 final-year medical students into the study, with 33 randomized to the face-to-face teaching group (control group), and 29 to the WSSL group(case group) according to their student number. The baseline demographic characteristics of the two groups were comparable. The mean score at the clinical competency assessment of the control group was 4.8/5 (range 4-5) and that of the case group was 4.7/5 (range 4-5) (p = 1). There were no difficulties with program or hardware installation reported by the WSSL students. CONCLUSIONS: Surgical skills performance was comparable between students who were taught by the WSSL and those taught by conventional face-to-face tutorials.

Beta-amyloid deposition around hepatic bile ducts is a novel pathobiological and diagnostic feature of biliary atresia.

BACKGROUND AND AIMS: Biliary atresia (BA) is a poorly understood and devastating obstructive bile duct disease of newborns. It is often diagnosed late, is incurable and frequently requires liver transplantation. In this study, we aimed to investigate the underlying pathogenesis and molecular signatures associated with BA. METHODS: We combined organoid and transcriptomic analysis to gain new insights into BA pathobiology using patient samples and a mouse model of BA. RESULTS: Liver organoids derived from patients with BA and a rhesus rotavirus A-infected mouse model of BA, exhibited aberrant morphology and disturbed apical-basal organization. Transcriptomic analysis of BA organoids revealed a shift from cholangiocyte to hepatocyte transcriptional signatures and altered beta-amyloid-related gene expression. Beta-amyloid accumulation was observed around the bile ducts in BA livers and exposure to beta-amyloid induced the aberrant morphology in control organoids. CONCLUSION: The novel observation that beta-amyloid accumulates around bile ducts in the livers of patients with BA has important pathobiological implications, as well as diagnostic potential. LAY SUMMARY: Biliary atresia is a poorly understood and devastating obstructive bile duct disease of newborns. It is often diagnosed late, is incurable and frequently requires liver transplantation. Using human and mouse 'liver mini-organs in the dish', we unexpectedly identified beta-amyloid deposition - the main pathological feature of Alzheimer's disease and cerebral amyloid angiopathy - around bile ducts in livers from patients with biliary atresia. This finding reveals a novel pathogenic mechanism that could have important diagnostic and therapeutic implications.

Risk factors for the development of post-operative enterocolitis in short segment Hirschsprung's disease.

AIM OF THE STUDY: The objective of this study is to identify risk factors associated with the development of post-operative enterocolitis (HAEC), in short segment Hirschsprung's disease (HSCR-S). METHODS: A retrospective study was carried out for post-operative patients with HSCR-S from 1997 to 2017. HSCR-S was defined as the most proximal extension of aganglionosis limited to the sigmoid colon. An episode of HAEC was defined as the presence of (1) vomiting or explosive diarrhea; (2) abdominal distension; (3) fever and (4) leukocytosis. Risk factors for the development of HACE were determined using multivariate logistic regression. MAIN RESULTS: The medical records of 96 patients were reviewed. The overall incidence of HAEC was 20.8% (n = 20) and 65.0% (n = 13) of HAEC occurred within the first year of operation. After a univariate logistic regression analysis, three risk factors for HAEC were identified: (1) presence of other major anomalies [OR: 1.43 (1.12-2.32), p = 0.041]; (2) creation of pre-operative defunctioning stoma [OR: 2.28 (1.47-3.23), p = 0.035]; (3) extension of aganglionosis to the sigmoid colon [OR: 1.89 (1.05-3.19), p = 0.049]. After multivariate logistic regression analysis, a significant association was demonstrated for creation of pre-operative defunctioning stoma [OR: 1.81 (1.08-3.22), p = 0.045] and extension of aganglionosis to the sigmoid colon [OR: 1.91 (1.37-2.98), p = 0.038]. CONCLUSIONS: The requirement of pre-operative defunctioning stoma and a more proximal extension of aganglionosis are risk factors for the development of post-operative HAEC in HSCR-S. Patients with these risk factors should be closely followed up especially during the first year after the operation.

Long-term Results and Quality of Life Assessment in Biliary Atresia Patients: A 35-Year Experience in a Tertiary Hospital.

OBJECTIVES: To review long-term transplant-free survival and quality of life (QOL) of patients with biliary atresia (BA). METHODS: A retrospective study reviewing all patients with Kasai operation between January 1, 1980 and December 31, 2015 was performed to evaluate the transplant-free survival. Subgroup analysis of patients older than 20 years was carried out to assess the QOL using the Short Form-36 Health Survey and incidences of disease-related complications. Comparison between patients with native and transplanted liver was performed using two-tailed independent samples t-test (P value < 0.05, significant). RESULTS: The 20-year Kaplan-Meier transplant-free survival of the 141 patients in our study was 51%. The subgroup analysis of long-term survivors revealed a trend of increased prevalence of complications like esophageal varices, portal hypertension, and recurrent admissions in the patient groups with raised serum bilirubin (SB).Thirty-one patients were successfully contacted for QOL assessment, 26 (16 with native liver and 10 with transplanted liver) responded (76.5%). BA patients who were documented to have active complications have a significantly lower vitality score (50.7 vs 57.5, P = 0.015). There was no statistically significant difference in the scores between the transplanted group and the disease-free control group. However, the native liver group achieved a lower score in both the general health section (42.9 vs 49.6, P = 0.029) and the overall physical component (49.6 vs 54.4, P = 0.037). CONCLUSIONS: A significant proportion of our patients survive with their native liver for more than 20 years. These long-term survivors may suffer from complications that impair their QOL. They require continuous life-long care.

Are all patients with short segment Hirschsprung's disease equal? A retrospective multicenter study.

BACKGROUND/PURPOSE: Short segment Hirschsprung's disease (HSCR) carries a better prognosis than long segment disease, but the definition of short is controversial. The objective of this study is to determine anatomically the extent of disease involvement that would be associated with a better functional outcome. METHODS: This is a retrospective multicenter (n = 3) study with patients (≥ 3 years) who had transanal pullthrough operation done for aganglionosis limited to the recto-sigmoid colon were reviewed. The extent of disease involvement and bowel resection was retrieved by reviewing the operative records as well as histopathological reports of the resected specimens. Clinical assessment was performed according to the criteria of a seven-itemed bowel function score (BFS) (maximum score = 20). Manometric assessment was performed with anorectal manometry. RESULTS: The study period started from 2003 to 45 patients were studied with median age at assessment = 52.0 months and operation = 3.0 months. The disease involvement was categorized into upper sigmoid-descending colon (DC) (n = 8), sigmoid colon (SC) (n = 12), upper rectum (UR) (n = 14) and lower rectum (LR) (n = 11) according to the level of normal biopsy result. There was no significant difference in the age of assessment between the four groups. The median BFSs in the DC, SC, UR and LR were 13, 15, 17 and 17, respectively (p = 0.01). Nine patients from the DC and SC groups reported soiling for more than twice per week. Sub-group analysis comparing patients with and without the entire sigmoid colon resected revealed worse functional outcomes in terms of the incidence of soiling (40.7 vs 22.2%, p = 0.05) and the BFS (14 vs 18, p = 0.04) in the former group. Anorectal manometry did not reveal any significant difference between the four groups, but a higher proportion of patients in the UR and LR groups appeared to have a normal sphincter resting pressure (DC vs SC vs UR vs LR = 62.5 vs 75.0 vs 85.7 vs 80.0%, p = 0.10). CONCLUSION: Patients with short segment HSCR are not equal at all. HSCR patients with aganglionosis limited to the rectum without the need of removing the entire sigmoid colon have a better bowel control and overall functional score. Less bowel loss and colonic dissection maybe the underlying reasons. Although future studies with a larger sample size and a longer follow-up period are required to validate the results of this study, it has provided a new insight to the current understanding of short segment disease in HSCR.