Elevated serum IL-34 is correlated with disease severity in patients with biliary atresia following Kasai portoenterostomy.

BACKGROUND: Biliary atresia (BA) is a severe congenital disorder with progressive obstructive cholangiopathy in young children. The inflammatory process has been recognized as one of the pathological mechanisms driving bile duct injury. Since interleukin-34 (IL-34) has been reportedly linked to several pathological liver disorders, including inflammation, the current study aimed to analyze circulating IL-34 and the association of circulating IL-34 with hepatic deterioration and clinical outcomes in post-Kasai BA children. METHODS: Circulating IL-34 levels were analyzed in 89 post-Kasai BA subjects and 45 healthy individuals using an ELISA. Liver stiffness (hardness) was measured by ultrasound elastography. RESULTS: Circulating IL-34 was substantially higher in BA children than in control individuals, particularly those with unfavorable outcomes including hepatic dysfunction, jaundice, and portal hypertension. In BA group, circulating IL-34 was positively correlated with liver stiffness (r = 0.515, p < 0.001), AST (r = 0.403, p < 0.001), ALT (r = 0.279, p = 0.008), total bilirubin (r = 0.224, p = 0.03), ALP (r = 0.255, p = 0.016), and serum IL-6 (r = 0.590, p < 0.001) but inversely correlated with albumin (r = -0.417, p < 0.001). Kaplan-Meier survival analysis showed that higher circulating IL-34 levels were significantly associated with reduced survival rates in BA subjects (p = 0.002). CONCLUSION: Higher circulating IL-34 values were directly associated with hepatic impairment and the BA severity, implicating thatserum IL-34 could be applied as a noninvasive marker for the monitoring of the severity in BA subjects following Kasai portoenterostomy and therapeutic efficacy.

Development of liver inflammatory injury in biliary atresia: from basic to clinical research.

Biliary atresia (BA) is a severe cholangiopathy in infants. It is characterized by inflammatory fibro-obliteration of the intra- and extrahepatic bile ducts. Although the restoration of bile flow can be successful after Kasai operation, the rapid progression of liver fibrosis can continue, leading to cirrhosis. It is believed that the progression of liver fibrosis in BA is exacerbated by complicated mechanisms other than the consequence of bile duct obstruction. The fibrogenic cascade in BA liver can be divided into three stages, including liver inflammatory injury, myofibroblast activation, and fibrous scar formation. Recent studies have revealed that the activation of an immune response following bile duct injury plays an important role in promoting the inflammatory process, the releasing of inflammatory cytokines, and the development of fibrogenesis in BA liver. In this article, we summarized the evidence regarding liver inflammatory injury and the possible mechanisms that explain the rapid progression of liver fibrosis in BA.

Systemic cytokine profiles in biliary atresia.

BACKGROUND: Inflammation and immune dysregulation persuade biliary duct injury in biliary atresia (BA), a leading cause of pediatric liver transplantation given lack of specific biomarkers. We aimed to determine associations between systemic cytokine profiles and clinical parameters in BA patients and to identify potential BA biomarkers. METHODS: Systemic levels of 27 cytokines were measured in 82 BA patients and 25 healthy controls using a multiplex immunoassay. Relative mRNA expressions of candidate cytokines in 20 BA livers and 5 non-BA livers were assessed using quantitative real-time PCR. RESULTS: Higher levels of 17 cytokines including IL-1ß, IL-6, IL-7, IL-8, IL-9, IL-2, IL-15, eotaxin, IP-10, MCP-1, MIP-1α, MIP-1ß, G-CSF, IL-1ra, IL-4, IL-5, and IL-10 and lower levels of IFN-α and PDGF were significantly associated with BA. In BA patients, increased levels of IL-7, eotaxin, IP-10, and IL-13 were significantly associated with unfavorable outcomes including jaundice, fibrosis, and portal hypertension. Indeed, systemic levels of those cytokines were significantly correlated with clinical parameters indicating jaundice, fibrosis, and hepatic dysfunction in BA patients. Out of 27 cytokines, 4 (IL-8, IP-10, MCP-1, and PDGF) had potential as sensitive and specific biomarkers of BA. Of these, higher IL-8 levels were significantly associated with reduced survival of BA. In BA livers, relative mRNA expressions of IL-8, IP-10, and MCP-1 were significantly up-regulated. CONCLUSIONS: Higher levels of several cytokines including inflammatory cytokines, immunomodulatory cytokines, chemokines, and anti-inflammatory cytokines and lower levels of growth factors would reflect inflammatory and immune responses related to BA development. Among 27 cytokines, plasma IL-8 might have great potential as a diagnostic and prognostic biomarker for BA.

A comparison of surgical site infections in children after stoma reversal between purse-string and linear closure.

BACKGROUND: To reduce the surgical site infections (SSI), the purse-string closure technique has been widely performed and has also been recommended in adult stoma reversal. However, for children, some debate still exists. This study aims to compare the SSI rates in children between the purse-string and the linear for the skin closure of stoma reversal. METHODS: The data were collected from pediatric patients, who had undergone either purse-string or linear closure for elective surgery of stoma reversal from two university hospitals between January 2016 and December 2019. RESULTS: The purse-string and linear closure had been performed on 31 and 45 patients, respectively. At 30 days after surgery, three patients in the purse-string closure group had developed SSI compared to 14 patients in the linear closure group (9.7 vs. 31.1%, p = 0.028). Furthermore, there had been no significant difference in the overall post-operative complications. In multivariate analysis, the SSI had been significantly lower in patients with purse-string closure (OR 0.21, 95% CI 0.05-0.86, p = 0.029). CONCLUSION: By employing the purse-string closure technique for skin closure of stoma reversal, there had been a significantly lower SSI rate compared to linear closure with no difference in the length of hospital stay.

Cartilage oligomeric matrix protein as a marker of progressive liver fibrosis in biliary atresia.

This study aimed to determine whether mRNA and protein levels of cartilage oligomeric matrix protein (COMP), a glycoprotein responsible for modulating homeostasis of extracellular matrix, in the systemic and local liver environments were associated with clinical parameters of biliary atresia (BA) patients and might serve as a biomarker for BA severity. COMP protein levels in the circulation of 96 BA patients and 56 healthy controls and its mRNA and protein expressions in the liver of 20 BA patients and 5 non-BA patients were evaluated using enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and immunohistochemistry, respectively. In the circulation of BA patients, COMP levels were significantly higher than those in healthy controls. Compared with early-stage BA patients, those with advanced-stage including jaundice, fibrosis, and hepatic dysfunction had significantly increased circulating COMP levels. Raised circulating COMP levels were found to be independently correlated with degree of liver fibrosis. Survival analysis showed that elevated circulating COMP levels were significantly associated with decreased survival of BA patients. Receiver-operating characteristic curve analysis unveiled a diagnostic value of circulating COMP as a non-invasive biomarker of BA (AUC = 0.99), with a sensitivity of 100.0% and a specificity of 98.2%. In the liver, both COMP mRNA and protein expressions of BA patients with fibrosis were significantly greater than those of BA patients without fibrosis and non-BA patients. Collectively, increased circulating COMP might reflect unfavorable outcome of BA patients and have potential as a novel biomarker for the disease severity following Kasai-operation.

Nasogastric decompression after intestinal surgery in children: a systematic review and meta-analysis.

PURPOSE: Postoperative nasogastric decompression has been routinely used after intestinal surgery. However, the role of nasogastric decompression in preventing postoperative complications and promoting the recovery of bowel function in children remains controversial. This systematic review aimed to assess whether routine nasogastric decompression is necessary after intestinal surgery in children. METHODS: A systematic review was conducted following the PRISMA guideline. Literature search was performed in electronic databases including PubMed, Embase, CENTRAL, and Web of science. Studies comparing outcomes between children who underwent intestinal surgery with postoperative nasogastric tube (NGT) placement (NGT group) and without postoperative NGT placement (no NGT group) were included. RESULTS: Six studies were eligible for inclusion criteria including two randomized controlled trials (RCT) and four comparative observational studies. The overall rate of postoperative anastomotic leak was 0.6% (1/179) in NGT group and 0.9% (2/223) in no NGT group. The overall rate of wound dehiscence was 2.4% (4/169) in NGT group and 1.6% (4/245) in no NGT group. Meta-analysis of two RCTs in children undergoing elective intestinal surgery showed significant increase of mild vomiting in no NGT group compared with NGT group (OR 3.54 95% CI 1.04, 11.99) but no significant difference in persistent vomiting requiring NGT reinsertion (OR 3.11 95% CI 0.47, 20.54), abdominal distension (OR 2.36 95% CI 0.34, 16.59), NGT reinsertion (OR 3.11 95% CI 0.47, 20.54), wound infection (OR 1.63 95% CI 0.49, 5.48) and time to return of bowel movement (MD - 0.14 95% CI - 0.45, 0.17). There was no incidence of anastomotic leak in these 2 RCTs. However, there was an incidence of NGT-related discomfort in NGT group, which ranged from 30 to 100% of children studied. CONCLUSION: Routine postoperative nasogastric decompression can be omitted in children undergoing intestinal surgery due to no benefit in preventing postoperative complications while increasing patient discomfort.

Human amniotic fluid stem cells attenuate cholangiocyte apoptosis in a bile duct injury model of liver ductal organoids.

PURPOSE: Biliary atresia (BA) is a fibro-obliterative cholangiopathy that involves both extrahepatic and intrahepatic bile ducts in infants. Cholangiocyte apoptosis has an influence on the fibrogenesis process of bile ducts and the progression of liver fibrosis in BA. Human amniotic fluid stem cells (hAFSCs) are multipotent cells that have ability to inhibit cell apoptosis. We aimed to investigate whether hAFSCs have the potential to attenuate cholangiocyte apoptosis and injury induced fibrogenic response in our ex vivo bile duct injury model of liver ductal organoids. METHODS: The anti-apoptotic effect of hAFSCs was tested in the acetaminophen-induced injury model of neonatal mouse liver ductal organoids (AUP #42681) by using direct and indirect co-culture systems. Cell apoptosis and proliferation were evaluated by immunofluorescent staining. Expression of fibrogenic cytokines was analyzed by RT-qPCR. Data were compared using one-way ANOVA with post hoc test. RESULTS: In our injury model, liver ductal organoids that were treated with hAFSCs in both direct and indirect co-culture systems had a significantly smaller number of apoptotic cholangiocytes and decreased expression of fibrogenic cytokines, transforming growth factor beta-1 (TGF-ß1) and platelet-derived growth factor-BB (PDGF-BB). Moreover, hAFSCs increased cholangiocyte proliferation in injured organoids. CONCLUSION: hAFSCs have the ability to protect the organoids from injury by decreasing cholangiocyte apoptosis and promoting cholangiocyte proliferation. This protective ability of hAFSCs leads to inhibition of the fibrogenic response in the injured organoids. hAFSCs have high therapeutic potential to attenuate liver fibrogenesis in cholangiopathic diseases such as BA.

Decreased circulating clusterin reflects severe liver complications after hepatoportoenterostomy of biliary atresia.

This study aimed to determine whether circulating levels of clusterin (CLU), an extracellular chaperone implicated in cholestatic and fibrotic processes, are associated with clinical parameters of post-operative BA patients and could serve as a BA biomarker. Ninety-six BA patients and 56 healthy controls were recruited. Circulating CLU levels were measured using enzyme-linked immunosorbent assay. Circulating CLU levels were significantly reduced in BA patients - especially those with worse outcomes including jaundice, severe liver fibrosis, and late-stage of hepatic dysfunction. Multivariate linear regression analysis revealed that circulating CLU levels were negatively associated with outcome parameters indicating jaundice status, degree of fibrosis, and liver dysfunction, but positively correlated with serum albumin and platelet number of BA patients. Lower circulating CLU levels were considerably associated with poor survival of post-operative BA patients. Receiver-operating characteristic curve analysis demonstrated a diagnostic value of circulating CLU as a non-invasive indicator for poor outcomes of BA patients (AUC = 0.85), with a sensitivity of 81.5% and a specificity of 73.5%. All findings indicate that reduced circulating CLU might reflect poor outcomes of BA patients and have potential as a novel biomarker for the disease severity following Kasai-operation.

A novel model of injured liver ductal organoids to investigate cholangiocyte apoptosis with relevance to biliary atresia.

PURPOSE: The fibrogenic process in cholangiopathic diseases such as biliary atresia (BA) involves bile duct injury and apoptosis of cholangiocytes, which leads to the progression of liver fibrosis into liver cirrhosis and can result in end-staged liver disease. Recent advances in the development of organoids or mini-organ structures have allowed us to create an ex vivo injury model of the bile duct that mimics bile duct injury in BA. The aim of this experimental study was to develop a novel model of injured intrahepatic cholangiocytes as this can be relevant to BA. Our new model is important for studying the pathophysiological response of bile ducts to injury and the role of cholangiocytes in initiating the fibrogenic cascade. In addition, it has the potential to be used as a tool for developing new treatment strategies for BA. METHODS: Liver ductal organoids were generated from the liver of healthy neonatal mouse pups. Intrahepatic bile duct fragments were isolated and cultured in Matrigel dome. Injury was induced in the organoids by administration of acetaminophen in culture medium. The organoids were then evaluated for fibrogenic cytokines expression, cell apoptosis marker and cell proliferation marker. RESULTS: Organoids generated from intrahepatic bile duct fragments organized themselves into single-layer epithelial spheroids with lumen on the inside mimicking in vivo bile ducts. After 24-h exposure to acetaminophen, cholangiocytes in the organoids responded to the injury by increasing expression of fibrogenic cytokines, transforming growth factor beta-1 (TGF-ß1) and platelet-derived growth factor-BB (PDGF-BB). This fibrogenic response of injured organoids was associated with increased cholangiocyte apoptosis and decreased cholangiocyte proliferation. CONCLUSION: To our knowledge this is the first description of cholangiocyte injury in the organoids derived from intrahepatic bile ducts. Our injury model demonstrated that cholangiocyte apoptosis and its fibrogenic response may play a role in initiation of the fibrogenic process in cholangiopathic diseases such as BA. These findings are important for the development of novel therapy to reduce cholangiocyte apoptosis and to halt the early fibrogenic cascade in liver fibrogenesis. This novel injury model can prove very valuable for future research in biliary atresia.

Hepatic expression of HGF/C-met and native liver survival in biliary atresia.

BACKGROUND: The prognosis of biliary atresia (BA) remains difficult to predict. This study evaluated the roles of hepatocyte growth factor (HGF) and its receptor (C-met) towards clinical outcome and native liver survival. METHODS: Hepatic HGF and C-met expression were determined using immunohistochemistry from liver biopsies of 41 BA patients during Kasai operation, and 17 non-cholestatic patients. The HGF and C-met expression was visually scored as per its intensity and percentage of stained area. BA patients were classified as high- and low-HGF and C-met receptor status. Native liver survival was compared between the two groups at 3-year follow-up. Data are shown as median and range. MAIN RESULTS: Median age of BA patients was 2 (1-6) months. Hepatic HGF and C-met staining scores of BA patients were higher than those of non-cholestatic patients (P < 0.0001). There was a correlation between HGF and C-met staining scores (spearman r = 0.77, P < 0.0001). However, there was no association between their expression and early outcome at 6 months post-op. Mean follow-up time was 68.6 months. Survival analysis revealed that native liver survival at 1 year and 3 years were 88% and 77%, respectively. Additionally, 82.6% (19/23) of patients in the low-HGF group survived with native liver, compared with 66.7% (10/15) of those in high-HGF group (P = 0.436). For C-met expression, 78.6% (22/28) of low-score and 70% (7/10) of high score groups survived with native liver (P = 0.673). CONCLUSIONS: Strong expression of hepatic HGF and its receptor in BA patients was demonstrated. However, the expression was not associated with the early outcome and native liver survival. These results suggest that HGF involved in the liver pathology of BA but its expression cannot be used as a prognostic indicator. Small sample size of patients was a main limitation. Further studies are warranted to validate our findings.

Intestinal organoids in infants and children.

Recent advances in culturing of intestinal stem cells and pluripotent stem cells have led to the development of intestinal organoids. These are self-organizing 3D structures, which recapitulate the characteristics and physiological features of in vivo intestinal epithelium. Intestinal organoids have allowed the development of novel in vitro models to study various gastrointestinal diseases expanding our understanding of the pathophysiology of diseases and leading to the development of innovative therapies. This article aims to summarize the current usage of intestinal organoids as a model of gastrointestinal diseases and the potential applications of intestinal organoids in infants and children. Intestinal organoids allow the study of intestinal epithelium responses to stress factors. Mimicking intestinal injury such as necrotizing enterocolitis, intestinal organoids increases the expression of pro-inflammatory cytokine genes and shows disruption of tight junctions after they are injured by lipopolysaccharide and hypoxia. In cystic fibrosis, intestinal organoids derived from rectal biopsies have provided benefits in genetic studies and development of novel therapeutic gene modulation. Transplantation of intestinal organoids via enema has been shown to rescue damaged colonic epithelium in mice. In addition, tissue-engineered small intestine derived from intestinal organoids have been successfully established providing a potential novel treatment and a new hope for children with short bowel syndrome.

Hepatic glypican-3 and alpha-smooth muscle actin overexpressions reflect severity of liver fibrosis and predict outcome after successful portoenterostomy in biliary atresia.

BACKGROUND: Glypican-3 plays a vital role in regulating embryonic morphogenesis of the liver. This study aimed to investigate associations of hepatic expressions of glypican-3 and alpha-smooth muscle actin with clinical parameters in biliary atresia. METHODS: Liver specimens were obtained from 20 biliary atresia infants and 7 non-biliary atresia controls. Relative mRNA expressions of glypican-3, alpha-smooth muscle actin, and signaling molecules of Wnt/ß-catenin were measured using real-time polymerase chain reaction. Protein expressions of glypican-3 and alpha-smooth muscle actin were examined using immunohistochemistry. Masson's trichrome staining was conducted to evaluate the stage of liver fibrosis. RESULTS: Up-regulation of glypican-3 mRNA expression was observed in biliary atresia livers, and its expression was positively associated with alpha-smooth muscle actin, ß-catenin, c-Myc, and cyclin D-1. Immunostaining scores of glypican-3 and alpha-smooth muscle actin were significantly increased in biliary atresia livers. Biliary atresia patients with poor outcomes had significantly greater glypican-3 expression than those with good outcomes, consistent with hepatic alpha-smooth muscle actin expression analysis. Hepatic glypican-3 expression was associated with age, albumin, aspartate transaminase, and alkaline phosphatase in biliary atresia patients, while hepatic alpha-smooth muscle actin expression was correlated with alkaline phosphatase in the patients. Moreover, glypican-3 and alpha-smooth muscle actin expressions were positively associated with fibrosis stage in biliary atresia livers. There was a positive relationship between glypican-3 and alpha-smooth muscle actin expression in biliary atresia livers. Combined high expressions of glypican-3 and alpha-smooth muscle actin were associated with poor survival. CONCLUSION: Hepatic overexpressions of glypican-3 and alpha-smooth muscle actin were associated with hepatic dysfunction and the degree of liver fibrosis in biliary atresia.

Axillary and elbow lymph node metastasis arising after complete excision of microcystic adnexal carcinoma of a hand: A rare presentation.

INTRODUCTION: Microcystic adnexal carcinoma (MAC), a malignant transformation of adnexal structures, constitutes a rare locally aggressive malignancy of skin. Generally, the disease is associated with local invasion and distant metastases are extremely rare. We presented a case of MAC with distant metastasis after adequate wide excision. PRESENTATION OF CASE: A 65-year-old man presented with a scar-like lesion at his left hand's middle finger. As pathologic result from incisional biopsy confirmed MAC, the patient was then treated with ray amputation. Eight years later, there was a presence of scar changes. There was a palpable node at medial epicondyle and presence of enlarged lymph nodes at axilla by imaging with Computed tomography (CT) scan. Following left hand amputation and node dissection at elbow and axillary region, pathologic examination confirmed recurrence and metastasis of MAC. He went through adjuvant radiation with a complete response. At present, two years after surgery, he remains in complete remission. DISCUSSION: The presence of a recurrent MAC with distant lymph node metastasis after primary surgery is rare. The metastatic route as presented with the positive nodes at elbow and axilla could be explained the spreading via lymphatic system. CONCLUSION: MAC arising at a hand may require wider excision in order to achieve best result. Although this malignancy is a slowly progressive disease, distant metastasis should always be concerned, especially when there are suspicious presentations. CT scan will render more details and make more precise diagnosis in the suspicious situation.

Tension pneumoperitoneum caused by rupture of intraabdominal soft tissue emphysema in a child supported with high-frequency oscillatory ventilation: a case report.

BACKGROUND: We reported a case with tension pneumoperitoneum while being on high-frequency oscillatory ventilation. CASE PRESENTATION: A 12-month-old Thai girl presented with acute respiratory distress syndrome, septic shock, and bacterial pneumonia. Although supported with mechanical ventilation, she still had severe hypoxia. She was then transitioned to high-frequency oscillatory ventilation. During a weaning period on day 7, she developed left tension pneumothorax requiring intercostal drainage and a markedly large amount of pneumoperitoneum. In spite of a bedside abdominocentesis, her abdomen was still tense and her hemodynamics was unstable. Subsequently, to exclude hollow viscus perforation, diaphragmatic injury caused by intercostal drainage, or abdominal compartment syndrome, she was transferred for surgery. There was no intestinal perforation. Postoperatively, she was on oxygen therapy, on chest physical therapy, and kept hemodynamically stable until she had recovered. CONCLUSION: A case of tension pneumoperitoneum probably caused by high-frequency oscillatory ventilation was reported. Awareness of this condition should be included in the differential diagnosis.

A challenge in diagnosis and management of ulcerative colitis in elderly patient with atypical presentation: A reported case.

INTRODUCTION: Recognition of elderly-onset ulcerative colitis (UC) remains poor as the differential diagnosis in older patients with acute abdominal pain and bloody diarrhea is extensive and UC is generally not the obvious cause. A typical presentation in an elderly patient with acute severe UC can mimic surgical abdomen. PRESENTATION OF CASE: An 80-year-old female had been presented with high grade fever, abdominal pain and diarrhoea. Physical examination showed sign of peritonitis and severe hypotension. A provisional diagnosis of perforated sigmoid diverticulitis was made. However, at the theater, there was only turbid yellowish ascites at cal-de-sac. Consequently, colonoscopy was performed and revealed continuous and circumferential erythematous with friable mucosa and multiple shallow ulcer along upper left side colon. Histologic examination of the colonic tissue was consistent with UC. DISCUSSION: As UC is uncommon in Thailand and clinical features of elderly-onset UC are much more non-specific; as a result, misdiagnosis at initial presentation is more common in elderly patients (60%) than that in younger population (15%). These might result in an unnecessary exploratory laparotomy; however, computed tomography scan can reduce the risk of that event. CONCLUSION: The diagnosis of severe acute UC in elderly patients with acute abdomen had been complicated by the distinctive physiology of this aged group with atypical presentation and markedly unreliable physical examination. Eventually, severe UC should always be kept in mind with a circumstance of abdominal pain in geriatric population.

A giant jejunal gastrointestinal stromal tumor misconceived as pancreatic cystic neoplasm: A case report.

INTRODUCTION: Gastrointestinal stromal tumors (GISTs), although not common in gastrointestinal (GI) tumors, constitute the most frequent mesenchymal tumors of the GI tract. This report describes a patient with a large sporadic GIST at proximal jejunum that mimicked the pancreatic cystic neoplasm. CASE PRESENTATION: We report a 59-year-old female patient with unexplained weight loss and palpable left upper quadrant abdominal mass for 6 months. Computed tomography (CT) scan demonstrated a heterogeneously mass measuring 10 cm in a maximal diameter at pancreatic body and tail. Laparotomy was done, and the tumor was found at proximal jejunum closed to the ligament of Treitz, so en bloc resection of the tumor was done. The pathological and immunohistochemical study confirmed GISTs. DISCUSSION: Although most GISTs are originated from the intestine, they frequently arise from the stomach, the duodenum and rarely from the jejunum. And jejunal GISTs are usually asymptomatic. The misdiagnosis as mucinous cystadenoma of this case might be due to the proximity of the tumor to the body and tail of pancreas, and compressing the adjacent organ due to its large size. CONCLUSION: GISTs are most frequently small and arising from the stomach. GISTs are rarely present as a large tumor of the jejunum, and particularly mimicked a pancreatic tumor.

Tuberculous peritonitis in a cerebral palsy patient: A challenge in diagnosis and management.

INTRODUCTION: Diagnosis of tuberculous peritonitis (TBP) in a normal person, although possible, is often difficult to make because of its non-specific symptoms and signs. However, establishing a diagnosis of TBP in a patient with cerebral palsy (CP) does not seem to be possible due to impaired mental development accompanied by communication problems. PRESENTATION OF CASE: A 19-year-old spastic man diagnosed with CP presented with fever and a nonverbal complaint of abdominal pain. The conditions were hard to evaluate due to his mental status. Abdominal radiography showed dilatation of both small and large bowels, and a subsequent computed tomography (CT) scan did not provide any additional information. With respect to a common suspected cause, a diagnosis of perforated appendicitis was established. However, at the theatre, there was only bowel dilatation with multiple small nodules at the serosa of small and large bowels. Postoperatively, polymerase chain reaction and culture revealed Mycobacterium tuberculosis, thereby leading to a diagnosis of TBP. DISCUSSION: Due to spasticity caused by CP, on examination, the patient presented with board-like rigidity, from which a diagnosis of a surgical condition was established. The misdiagnosis of an acute abdomen situation had let the patient to undergo an unnecessary exploration. To our knowledge, there has not been a report of TBP in a CP patient. CONCLUSION: The diagnosis of TBP had been complicated by the presence of CP in the reported case. The underlying CP not only preclude the diagnosis of TBP, but also produced symptoms that mimicked a condition requiring surgery.

Leukocyte mitochondrial DNA copy number as a potential biomarker indicating poor outcome in biliary atresia and its association with oxidative DNA damage and telomere length.

Biliary atresia (BA) is a chronic obstructive liver disease, leading to advanced liver failure. Mitochondria dysfunction-mediated aberrant telomere length has been implicated in various pathological processes including cholestasis. Herein, we aimed to investigate associations between mitochondrial DNA (mtDNA) copy number, oxidative DNA damage, telomere length, and disease severity in BA patients. mtDNA copy number and relative telomere length (RTL) were assessed using real-time PCR. Circulating 8-hydroxy-2'-deoxyguanosine (8-OHdG) was measured using ELISA. Our findings showed that BA patients had significantly lower mtDNA copy number and RTL than healthy controls, whereas plasma 8-OHdG levels were significantly elevated in BA patients. mtDNA copy number was remarkably reduced in advanced BA patients. Furthermore, mtDNA copy number was independently associated with age and degree of liver fibrosis in BA patients. Decreased mtDNA copy number was significantly associated with elevated risks of BA, severe fibrosis, jaundice, and hepatic dysfunction. Low mtDNA copy number can be utilized to distinguish patients with poor-outcome from those with good-outcome. Survival curve analysis revealed that low mtDNA copy number was significantly associated with poor survival of BA patients. Interestingly, there was a positive association between mtDNA copy number and plasma 8-OHdG in BA patients, while a negative association of mtDNA copy number with RTL was observed in BA patients. Alternatively, RTL was negatively correlated with plasma 8-OHdG in BA patients. These data demonstrated relationships between leukocytes mtDNA copy number, oxidative stress, telomere length, and clinical parameters in BA patients. Accordingly, our findings indicate that mtDNA copy number may serve as a potential biomarker reflecting BA severity.

Hepatic autotaxin overexpression in infants with biliary atresia.

BACKGROUND: Autotaxin (ATX) is a secreted glycoprotein that is involved in the development of hepatic fibrogenesis via the enzymatic production of lysophosphatidic acid. The aim of this study was to investigate hepatic expression of ATX in biliary atresia (BA) compared with non-BA liver controls and to examine the association between ATX expression and clinical outcome in BA. METHODS: Liver specimens from BA infants (n = 20) were compared with samples from infants who underwent liver biopsy for reasons other than BA (n = 14) and served as controls. Relative mRNA and protein expression of ATX were quantified using real-time polymerase chain reaction (PCR) and immunohistochemistry. Masson's Trichrome staining was performed to determine the degree of liver fibrosis. RESULTS: Quantitative real-time PCR demonstrated overexpression of ATX mRNA in BA livers. In immunohistochemical evaluation, ATX was positively stained on the hepatic parenchyma and the biliary epithelium in BA patients, as compared to non-BA controls. The immunostaining score of ATX in BA livers was also significantly higher than that observed in non-BA livers (P < 0.001). Subgroup analysis revealed that ATX expression in the patients with poor outcomes was significantly greater than in those with good outcomes (P = 0.03). Additionally, there was a positive correlation between hepatic ATX expression and Metavir fibrosis stage in BA livers (r = 0.79, P < 0.001). DISCUSSION: This study found that mRNA and protein expression of ATX were increased in BA livers. High hepatic ATX expression at the time of Kasai operation was associated with liver fibrosis and outcome in BA, suggesting that ATX may serve a role as a promising biomarker of the prognosis in biliary atresia.

Prognostic values of serum bilirubin at 7th day post-Kasai for survival with native livers in patients with biliary atresia.

BACKGROUND: Biliary atresia (BA) is a serious liver disease with uncertain prognosis. The objective of this study was to investigate prognostic values of the >20 % decrease in serum total bilirubin (TB) at 7th day post-op regarding early outcome and 5-year survival with native liver in BA. METHODS: Biliary atresia patients undergoing Kasai operation between 2000 and 2014 were reviewed. The ratio of serum TB at 7th day post-op to pre-op TB levels (TB7/TB0) was calculated for every patient. TB7/TB0 ratio of <0.8 indicated the >20 % decrease in serum TB. At 6th month following Kasai operation, outcome of BA patients were categorized into good outcome (TB < 2 mg % or clinically jaundice free) and poor outcome (TB > 2 mg % or clinically jaundice). For outcome analysis, logistic regression was used. For survival analysis, Cox regression was applied. RESULTS: There were 133 BA patients (M:F = 68:65) undergoing Kasai operation. Median age at surgery was 79 days. BA patients with TB7/TB0 ratio of <0.8 were found in 38 %. Outcome at 6-month post-op could be evaluated in 126 patients (good: poor = 68:58). The 1-, 3- and 5-year survival rates with native livers were 85, 70 and 65 %, respectively. The median overall survival with native livers was 164 months. Median follow-up time was 87 months. Logistic regression showed that gender and age at operation were not significant factors impacting on early outcome (p > 0.05). However, TB7/TB0 ratio of <0.8 was an independent factor for good outcome (Odds ratio = 3.0, p = 0.006). Cox regression analysis demonstrated that 5-year survival rate was significantly correlated with TB7/TB0 ratio of <0.8 (HR = 0.46, 95 % CI 0.23-0.91, p = 0.025) and outcome at 6th month post-op (HR = 0.05, 95 % CI 0.01-0.15, p < 0.001). CONCLUSIONS: The >20 % decrease in serum TB at 7th day post-Kasai is a predictor for good outcome. BA patients with TB7/TB0 of <0.8 had 5-year survival with native livers significantly higher than those with the ratio of >0.8.