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Biomedical subjects

Mark D Stringer

Publications and source records attributed to Mark D Stringer.

At least 19 recordsLinked to original sources
PubMed2007

Gallbladder mucin production and calcium carbonate gallstones in children.

In contrast to adults, calcium carbonate gallstones are relatively common in children. Their pathogenesis is poorly understood. Cystic duct obstruction promotes calcium carbonate formation in bile and increases gallbladder mucin production. We tested the hypothesis that mucin producing epithelial cells would be increased in gallbladders of children with calcium carbonate gallstones. Archival gallbladder specimens from 20 consecutive children who had undergone elective cholecystectomy for cholelithiasis were examined. In each case, gallstone composition was determined by Fourier transform infrared microspectroscopy. Gallbladder specimens from six children who had undergone cholecystectomy for conditions other than cholelithiasis during the same period were used as controls. Multiple sections were examined in a blinded fashion and scored semiquantitatively for mucin production using two stains (alcian blue and periodic acid-Schiff). Increased mucin staining was observed in 50% or more epithelial cells in five gallbladder specimens from seven children with calcium carbonate stones, compared to 5 of 13 with other stone types (P = 0.17) and none of the control gallbladders (P = 0.02). Gallbladders containing calcium carbonate stones were significantly more likely than those containing other stone types or controls to contain epithelial cells with the greatest mucin content (P = 0.03). Gallbladders containing calcium carbonate stones were also more likely to show the ulcer-associated cell lineage. These results demonstrate an increase in mucin producing epithelial cells in gallbladders from children containing calcium carbonate stones. This supports the hypothesis that cystic duct obstruction leading to increased gallbladder mucin production may play a role in the development of calcium carbonate gallstones in children.

Adolescent↗
PubMed2006

Solid pseudopapillary tumour of the pancreas: diverse presentation, outcome and histology.

CONTEXT: Solid pseudopapillary tumour of the pancreas is an uncommon tumour, which predominantly occurs in young females and is of unknown origin. CASE REPORT: We describe five cases with diverse clinical and/or histological features, including one unusually aggressive case resulting in early death. CONCLUSION: There is great variability in the presentation and clinical course of these tumours with further research needed to define their histogenesis and biological behaviour.

Adult↗
PubMed2006

Pediatric pancreatic hemangioma: a case report and literature review.

CONTEXT: The pancreas is an unusual site for a hemangioma in an infant. A child with obstructive jaundice caused by a pancreatic hemangioma is presented and management strategies for this benign tumor are discussed. CASE REPORT: A 5-month-old girl presented with a 2-week history of jaundice, pale stools and dark urine. Liver function tests confirmed obstructive jaundice. An abdominal ultrasound scan and magnetic resonance imaging showed an enhancing mass in the head of the pancreas. At laparotomy, a wedge biopsy of the pancreatic tumor was taken and a tube cholecystostomy inserted. Histological examination of the specimen revealed a pancreatic hemangioma with sclerotic features. The high volume of bile loss from the cholecystostomy proved problematic and biliary diversion with a Roux-en-y hepaticojejunostomy was therefore performed. The tumor subsequently regressed spontaneously and was no longer visible on follow-up imaging two years later. The child has since thrived. CONCLUSIONS: Pancreatic hemangiomas are rare and may cause diagnostic confusion. Pancreatic resection should be avoided since the natural history of these benign tumors is that of spontaneous involution. Various strategies can be used to manage any associated obstructive jaundice.

Female↗
PubMed2006

Does the pediatric end-stage liver disease score or hepatic artery resistance index predict outcome after liver transplantation for biliary atresia?

The pediatric end-stage liver disease score (PELD) was devised and validated as a tool for predicting mortality and morbidity in children with chronic liver disease waiting for a liver transplant (LT). It has become a useful guide for prioritizing organ allocation in the United States. The hepatic artery resistance index (HARI) also predicts waiting list mortality in children with biliary atresia. Does the PELD score or HARI predict outcome after LT for biliary atresia? Twenty consecutive children who underwent LT for biliary atresia between 2001 and 2005 were reviewed. Their PELD score was calculated periodically between listing and transplantation and HARI was measured at listing. Outcome variables were operative blood transfusion requirements, ICU stay and postoperative stay. Median age at LT was 8 (2-204) months. After allowing for the type of graft, the PELD score and the change in PELD score between listing and LT (deltaPELD) showed no significant correlation with blood transfusion requirements, but both the PELD score at listing and deltaPELD showed a trend toward a statistically significant positive correlation with overall hospital stay. Pre-transplant HARI showed a statistically significant positive correlation with the PELD score at listing (r = 0.46, p = 0.05) but did not correlate significantly with hospital stay. In this relatively small but homogeneous group of children undergoing LT for biliary atresia, PELD, and deltaPELD scores showed a trend toward a statistically significant positive correlation with overall hospital stay. However, neither PELD scores nor the pre-transplant HARI showed a definite correlation with outcome. Post-transplant complications are probably more important factors determining ICU and hospital stay in children currently transplanted for biliary atresia.

Adolescent↗
PubMed2006

Successful conservative management of idiopathic fibrosing pancreatitis in children.

UNLABELLED: Idiopathic fibrosing pancreatitis, a rare cause of obstructive jaundice and abdominal pain in children, which has certain features in common with the emerging entity of autoimmune pancreatitis as described in adults, has frequently been managed surgically. We present our experience of successful conservative management of this condition in children. Three children (6-12 years; two girls, one boy) presented with a short history of abdominal pain followed by obstructive jaundice. Abdominal ultrasonographic examination in each case showed dilated intrahepatic and common bile ducts with a bulky pancreas, predominantly the head. These findings were confirmed by magnetic resonance imaging. In two cases, the diagnosis of fibrosing pancreatitis was made by exclusion after extensive investigation. The third case had a percutaneous ultrasound-guided pancreatic needle biopsy. Two patients were managed by supportive medical therapy alone, whilst the third, with symptomatic obstructive jaundice, underwent temporary endoscopic stenting of the common bile duct. Cases have been followed-up for 12-49 months. There was complete clinical and biochemical resolution of obstructive jaundice in all three cases. Plasma bilirubin concentrations decreased to normal within 3-8 weeks. Serial abdominal imaging showed a gradual resolution of biliary dilatation and abnormal pancreatic morphology with subsequent pancreatic atrophy. Two children developed steatorrhoea that responded to pancreatic enzyme supplements, and one patient developed diabetes mellitus. None of the cases needed invasive surgery for diagnosis or management. CONCLUSION: With careful radiological and biochemical assessment and monitoring, invasive surgery can be avoided in the management of fibrosing pancreatitis. The eventual outcome is no different from reported surgically treated cases.

Abdominal Pain↗
PubMed2006

Elevated expression of IL2 is associated with increased infiltration of CD8+ T cells in biliary atresia.

AIM OF STUDY: Lymphocyte-mediated inflammation within the liver and bile ducts has been proposed as a potential mechanism in the pathogenesis of biliary atresia (BA). Recent reports have suggested that BA is associated with upregulation of TH1-type inflammatory cytokines. Quantitative real-time polymerase chain reaction (qrt-PCR) is a useful tool to assess immune cell density and cytokine gene expression in tissues. The aim of this study was to characterize the inflammation in BA by quantifying lymphocyte density and expression of TH1 cytokines such as IL2 and tumor necrosis factor alpha (TNF-alpha) in liver biopsies using qrt-PCR. METHODS: Total RNA was extracted from archival formalin-fixed paraffin-embedded liver biopsy specimens collected from three age-matched groups of patients: group I, nonsyndromic BA at the time of Kasai portoenterostomy (n = 10); group II, choledochal dilatation at the time of surgery (n = 2); group III, other cholestatic diseases including biliary hypoplasia and parenteral nutrition-associated cholestasis (n = 3). Qrt reverse transcription-PCR was performed to measure the relative levels of messenger RNA (mRNA) expression of CD4, CD8, IL2, and TNF-alpha. Their levels were normalized to the level of beta-actin expression. The numbers of CD4+ and CD8+ lymphocytes infiltrating portal tracts were also measured using immunohistochemistry. Data were expressed as median and ranges, and statistical comparison and correlation was by nonparametric test (Kruskal-Wallis and Spearman rank). RESULTS: CD8 mRNA expression was significantly increased in group I (median 0.26, range 0.11-6.29) compared with groups II and III (0.002, 0-0.004 and 0.02, 0-0.12) (P < .05). Levels of IL2 mRNA expression were also significantly increased in group I (1.22, 0.05-7.54) compared with groups II (0.58, 0-1.17) and III (0, 0-0.03) (P < .05). In contrast, there was no significant increase in CD4 and TNF-alpha expression in group I compared with groups II and III. There was a significant correlation between the number of CD8+ lymphocytes in portal tracts and the levels of CD8 mRNA expression. CONCLUSION: Increased expression of IL2 and increased CD8 T-cell infiltration in liver biopsy specimens from infants with BA suggest the possibility that IL2 plays a role in the pathogenesis of this condition.

Biliary Atresia↗
PubMed2006

Increased CXCR3 expression associated with CD3-positive lymphocytes in the liver and biliary remnant in biliary atresia.

BACKGROUND: Lymphocyte-mediated inflammatory damage of the bile ducts has been proposed as a potential mechanism in the pathogenesis of biliary atresia (BA). Chemokines regulate leukocyte migration and act as critical organizers of cell distribution in inflammatory responses. The aim of this study was to analyze the infiltration of T lymphocytes and the expression of a chemokine receptor, CXCR3, predominantly expressed on type 1 polarized T cells (T(H)1, T(C)1) in the liver and excised biliary remnants in infants with BA. METHODS: Immunohistochemistry for CD3, CD8, and CXCR3 was performed using liver biopsy specimens collected from the following 3 age-matched groups of patients: group 1, BA (nonsyndromic) at the time of Kasai portoenterostomy (n = 10); group 2, congenital choledochal dilatation (n = 2); and group 3, other cholestatic diseases including paucity of intrahepatic bile ducts and cholestasis (n = 3) related to total parenteral nutrition. Cellular staining on each section was graded from 0 to 4 and compared using nonparametric statistics. RESULTS: Infiltrating CD3+ and CD8+ lymphocytes in the portal tracts were significantly increased in group 1 (3.1 +/- 0.4, 2.8 +/- 0.4), compared with groups 2 (1.0 +/- 0.0, 1.0 +/- 0.0) and 3 (1.7 +/- 0.3, 1.5 +/- 0.5) (P < .01, P < .05). CXCR3+ mononuclear cells were significantly increased in group 1 (2.6 +/- 0.3) compared with groups 2 (0.5 +/- 0.5) and 3 (0.7 +/- 0.3) (P < .05). They were mainly found in the portal tracts with a similar distribution to CD3+ cells. CXCR3+ cells and CD3+ cells also showed a similar distribution in specimens of biliary remnants from just below the portal plate. CONCLUSIONS: Increased expression of CXCR3 associated with a significantly increased CD3 and CD8 T-cell infiltration suggests that CXCR3+ lymphocytes in a type 1 (T(H)1, T(C)1) cytokine milieu may play a role in the pathogenesis of BA.

Bile Ducts↗
PubMed2006

Ciliated hepatic foregut cyst.

A male infant was found to have a large congenital hepatic cyst, first noted in late gestation by prenatal ultrasound scan. The cyst communicated with the biliary tree and was eventually removed completely by an extended right hepatectomy. Histopathologic examination showed a thick-walled, unilocular cyst lined predominantly by ciliated, stratified squamous epithelium with an outer wall composed of smooth muscle cells and fibrous tissue. These features are diagnostic of a ciliated hepatic foregut cyst, a rare congenital malformation with histologic similarities to bronchogenic cysts. The young age of our patient, prenatal detection, large size of the cyst, and a clear communication with the biliary tree have not been previously described with ciliated hepatic foregut cysts.

Cilia↗
PubMed2005

Immediate extubation of children following liver transplantation is safe and may be beneficial.

BACKGROUND: Immediate tracheal extubation of selected adult patients after orthotopic liver transplant (OLT) is common practice. We hypothesized that selected children may be safely extubated immediately after OLT and avoid potentially deleterious effects of artificial ventilation and sedation. METHODS: After June 2002, we chose immediate extubation unless a specific contraindication was identified. Charts of all children undergoing OLT between June 2002 and February 2005 were reviewed to audit safety and outcome of this approach. Comparative data were obtained for children undergoing first elective OLT at other UK centers. RESULTS: Forty-six cadaveric liver transplants were performed in 40 patients: 26 of 34 (76%) elective transplants and 4 of 12 (33%) urgent transplants were extubated immediately after surgery. Eight of 14 (57%) children weighing less than 10 kg were successfully extubated. One child required reintubation after developing transfusion-related acute lung injury. There were no other events compromising patient or graft. Small recipient size, split/reduced grafts, preexisting respiratory disease, retransplantation, and acute liver failure did not individually preclude successful immediate extubation. After elective OLT, the mean duration of intensive care stay was significantly shorter in the extubated group than in those who were ventilated (2.5 vs. 6.1 days, P<0.01). All children receiving a liver transplant at other UK centers in 2003 were ventilated postoperatively. However, the median duration of intensive care stay (2 days) was the same as in our series. CONCLUSIONS: Immediate extubation of selected children after OLT is safe. It may enhance patient recovery, benefit graft physiology, and reduce intensive care requirement.

Child↗
PubMed2005

Kasai portoenterostomy--new insights from hepatic morphology.

BACKGROUND/PURPOSE: The aim of this paper was to investigate the mechanism of long-term biliary drainage after Kasai portoenterostomy by clinicopathologic study of hepatic morphology in explanted livers. METHODS: Explanted livers from 13 consecutive children undergoing transplantation for biliary atresia were examined in detail using a standardized protocol. Group 1 (n = 6) had no Kasai procedure before transplantation at a median age of 8 m. Group 2 (n = 4) were transplanted at a median age of 10 m after a failed Kasai portoenterostomy. Group 3 (n = 3) had a successful Kasai but required transplantation for complications of chronic liver disease at 12-14 years. Pathology findings were correlated with hepatic morphology determined by pretransplant magnetic resonance imaging. RESULTS: Large perihilar regenerative nodules (8-14 cm diameter) were observed in 2 patients after successful Kasai portoenterostomy, less well-defined perihilar nodules in group 2 patients, and no regenerative nodules in group 1. Microscopically, group 1 had diffuse biliary cirrhosis with evidence of progressive ductopenia during infancy. In group 2, perihilar regenerative nodules showed variable portal fibrosis but no cirrhosis and bile ducts were present with 68%-100% of hepatic arteries; in peripheral cirrhotic areas, bile ducts were absent in patients older than 9 m. The perihilar regenerative nodules in group 3 patients had a noncirrhotic architecture with preserved bile ducts, but the peripheral parenchyma was cirrhotic; one patient had diffuse macronodular cirrhosis. These morphologic findings correlated well with magnetic resonance images, highlighting the preservation of relatively normal perihilar liver architecture after successful Kasai portoenterostomy. CONCLUSIONS: Unoperated biliary atresia is associated with progressive intrahepatic ductopenia leading to diffuse biliary cirrhosis. Kasai portoenterostomy can result in the growth of large perihilar regenerative nodules, probably as a consequence of surviving intrahepatic ducts in this region. In some patients, long-term success after Kasai portoenterostomy may depend on hyperplasia of the perihilar liver.

Adolescent↗
PubMed2005

Preoperative vascular imaging in pediatric liver transplantation.

BACKGROUND/PURPOSE: There is a considerable variation in the use of vascular imaging techniques in the preoperative assessment of children scheduled for liver transplantation. Duplex Doppler ultrasound scan (US), magnetic resonance angiography (MRA), and conventional angiography are used to varying extents. The authors compared the results of preoperative vascular imaging studies with operative findings to determine their accuracy and usefulness. METHODS: Results of preoperative vascular imaging in 37 consecutive children undergoing cadaveric liver transplantation were compared with operative findings. Those undergoing relatively elective transplantations were investigated by US and MRA (group 1), whereas those requiring urgent transplants were assessed only by US (group 2). RESULTS: The median age of the cohort (15 boys; 22 girls) was 4 years (19 days to 16 years) and the median weight was 17 kg (2.9 to 82 kg). In group 1 (n = 26), 20 children had a normal-caliber, patent portal vein at transplant and 6 had a narrow but patent portal vein requiring venous reconstruction in 4. The sensitivity and specificity of MRA in the detection of an abnormally narrow portal vein were 100% (6/6) and 95% (19/20), respectively. If reversed or absent flow in the portal vein on US was taken as an indication of a potentially abnormal vein, the sensitivity and specificity of Doppler US were 83% (5/6) and 95% (19/20), respectively. Magnetic resonance angiography revealed arterial anomalies in 4 children but failed to detect small accessory hepatic arteries in 5. The single patient with an aberrant vena cava was identified by MRA. In group 2 (n = 11), venous findings at operation and on US were concordant in 10 (91%) cases; one infant with reversed flow in the portal vein on US had a thrombosed vein at surgery. Magnetic resonance angiography was useful in 2 patient groups: those with reversed flow on Doppler US or suspected portal vein thrombosis in whom an abnormal portal vein was present in 86% (6/7) and infants with the biliary atresia splenic malformation syndrome who had multiple venous and arterial anomalies. CONCLUSIONS: A detailed Doppler examination of the hepatic vasculature by an experienced sonographer/radiologist provides sufficient vascular imaging for most children scheduled for cadaveric liver transplantation. Routine MRA is recommended in children with the biliary atresia splenic malformation syndrome and in those with abnormal duplex Doppler US findings. Although there are limited data in this study, MRA is also valuable in children with Budd-Chiari syndrome, liver tumors, or a previous portosystemic shunt.

Adolescent↗
PubMed2005

A randomized controlled trial of elective preterm delivery of fetuses with gastroschisis.

BACKGROUND: Elective preterm delivery of the fetus with gastroschisis may help to limit injury to the extruded fetal gut and thus promote faster recovery of neonatal gut function and earlier hospital discharge. This hypothesis has not previously been tested in a prospective randomized controlled trial. METHODS: Between May 1995 and September 1999, all women referred to a single tertiary center before 34 weeks' gestation with a sonographically diagnosed fetal gastroschisis were invited to participate in a randomized controlled trial. Eligible patients were randomized to elective delivery at 36 weeks or to await the onset of spontaneous labor. The method of delivery was not prescribed by the trial. Primary outcome measures in the neonate were the time taken to tolerate full enteral feeding (150 mL/kg per day) and duration of hospital stay. RESULTS: Of 44 eligible women, 42 were randomized, 21 to elective delivery and 21 to await spontaneous labor. There were 20 liveborn infants in each group. Four babies in the elective group and 4 in the spontaneous group delivered before 36 weeks' gestation but were included in the analysis on an intention-to-treat basis. Mean gestational age at delivery was 35.8 weeks in the elective group and 36.7 weeks in the spontaneous group. Primary closure of the gastroschisis was achieved in a similar proportion (80%-85%) of infants in both groups. Two babies in the elective group died from short gut complications. In the survivors, there was a trend in favor of a shorter median time to achieve full enteral feeding (30.5 vs 37.5 days) and a shorter median duration of hospital stay (47.5 vs 53 days) in the elective group, but this was not statistically significant. These findings remained unaltered when the data were reanalyzed after (a) excluding infants with intestinal atresia or (b) excluding infants born before 36 weeks' gestation. CONCLUSIONS: Although limited by the small number of patients, this randomized controlled trial demonstrates no significant benefit from elective preterm delivery of fetuses with gastroschisis.

Adult↗
PubMed2005

Mesenchymal hamartoma of the liver: a systematic review.

Mesenchymal hamartoma of the liver is the second commonest benign liver tumor in children, yet its biology and pathogenesis are poorly understood. Cytogenetic studies have suggested that the tumor may be a neoplasm rather than a hamartoma. Typically, it presents as a large benign multicystic liver mass in a child younger than 3 years amenable to complete resection. However, its imaging characteristics are variable, ranging from a few large cysts to a solid mass occupying one or both lobes of the liver. In addition, the tumor occasionally contains angiomatous elements or is multifocal. Most tumors gradually increase in size, some reaching enormous proportions, which can make surgery challenging. Paradoxically, a few undergo incomplete spontaneous regression and, on rare occasions, others have shown malignant transformation to undifferentiated (embryonal) sarcoma. These unusual pathological and biological features must be taken into account when considering the management of affected individuals.

Adolescent↗
PubMed2005

Pancreatitis and pancreatic trauma.

Many pancreatic disorders in children benefit from a multidisciplinary approach. This is especially true for acute and chronic pancreatitis which has numerous and diverse etiologies. The current management of pancreatitis is reviewed, focusing on recent advances. Children with pancreatitis must be fully investigated, not least to select out those who benefit from specific surgical interventions. The treatment of pancreas divisum, pseudocysts, and fibrosing pancreatitis deserve particular consideration. Management of pancreatic injuries involving the main pancreatic duct is both variable and controversial. Treatment should be individualized depending on the site of injury, timing of referral, presence of associated injuries, and institutional expertise.

Acute Disease↗
PubMed2005

Multidisciplinary management of surgical disorders of the pancreas in childhood.

OBJECTIVES: To describe the frequency and range of pancreatic disorders in children requiring surgical intervention and to highlight the importance of multidisciplinary management. METHODS: An audit of all children under 17 years of age referred with surgical disorders of the pancreas or pancreatitis to a regional pediatric gastroenterology unit in the United Kingdom during a 10-year period. A retrospective chart review of clinical features, pathology and outcome was undertaken. RESULTS: Surgical intervention was required for the following pancreatic disorders: persistent hyperinsulinemic hypoglycemia of infancy (n = 4), pancreatic tumors (n = 5), pancreaticobiliary malunion (n = 12), pancreatic trauma (n = 6) and pancreatitis (n = 10). The indications for surgery in acute pancreatitis were a persistent pseudocyst (n = 1) and treatment of an underlying cause of pancreatitis (n = 4); in chronic pancreatitis, surgery was used to treat symptomatic pancreatic duct strictures (n = 4). One child died of a progressive lymphoma but all others who underwent surgery are alive and well. All 33 children with acute pancreatitis, including four with pancreatic necrosis, survived. CONCLUSIONS: Surgery for pancreatic disorders in children is rarely required but may be necessary a) for definitive management of primary pancreatic pathology, b) to treat sequelae of acute or chronic pancreatitis and c) to treat an underlying cause of pancreatitis. There is a broad spectrum of potential pathologies. These patients are best managed by a multidisciplinary team approach.

Acute Disease↗
PubMed2004

Informed consent and choice in cholecystectomy.

As patients and parents seek more information and the threat of litigation increases, the process of informed consent has assumed greater importance. Data from large adult experiences indicate that the risk of bile duct injury, although small, is greater with laparoscopic cholecystectomy (LC) than open cholecystectomy. This complication has not yet been documented in pediatric practice, where cholecystectomy is relatively uncommon. What method do parents and patients choose if consent is truly informed? Of 57 consecutive children undergoing cholecystectomy, an open procedure was specifically indicated in 20 (previous major gastrointestinal surgery in 11, concomitant major abdominal operation in four, and complex biliary tract disease in five) and LC in two (cystic fibrosis, severe autism). The remaining 35 patients were counseled in a standard manner about the relative merits of LC versus mini-cholecystectomy (MC) and allowed to choose. Specifically, they were informed that LC offers better cosmesis, less postoperative discomfort, and a shorter hospital stay, but in adults is associated with a slightly increased rate of bile duct injury (0.3-0.5% vs. 0.2%). All MCs were performed through a 4-cm incision. Parents chose LC in 23 cases and MC in 12. The median age of both groups was similar. No surgical complications occurred, and there were no conversions in the LC group. No patient had retained stones. LC patients were discharged home after a mean of 1.7 days and MC patients after 2.3 days (0.1 > p > 0.05). If an open or laparoscopic technique is not specifically indicated and if parents/patients are fully informed, a significant minority may opt for mini-cholecystectomy.

Adolescent↗