Splenic Malformation Research Articles

Biliary atresia with splenic malformation with associated ductal plate malformation and duodenal atresia: A case report.

Biliary atresia (BA) is the most common cause of the obstructive type of neonatal cholestasis that requires prompt surgical intervention. About 10% of neonates with BA have other congenital anomalies, of which splenic malformation (BASM) is a well-known distinct sub-group. There is sparse literature on the association of duodenal atresia and ductal plate malformation (DPM) in patients of BASM. We describe a BASM associated with DPM and duodenal atresia in a 35-day-old infant, who succumbed at 40 days, before portoenterostomy could be performed. Duodenal atresia can be one of the associated malformations associated with BASM and ductal plate abnormalities. In our case, the child did not survive.

Loss of zebrafish pkd1l1 causes biliary defects that have implications for biliary atresia splenic malformation.

Biliary atresia is a fibroinflammatory neonatal disease with no effective therapies. A subset of cases (10-20%) is associated with laterality defects - labeled biliary atresia splenic malformation (BASM) syndrome. Recently, whole-exome sequencing of patients with BASM identified deleterious variants in PKD1L1. PKD1L1 is involved in left-right axis determination; however, its role in cholangiocytes is unknown. We generated the pkd1l1hsc117 allele using CRISPR/Cas9 mutagenesis in zebrafish to determine the role of Pkd1l1 in biliary development and function. Wild-type and mutant larvae were assessed for laterality defects, biliary function and biliary tree architecture at 5 days post fertilization. pkd1l1hsc117 mutant larvae exhibited early left-right patterning defects. The gallbladder was positioned on the left in 47% of mutants compared to 4% of wild-type larvae. Accumulation of PED6 in the gallbladder, an indicator of hepatobiliary function, was significantly reduced in pkd1l1hsc117 mutants (46%) compared to wild-type larvae (4%). pkd1l1hsc117 larvae exhibited fewer biliary epithelial cells and reduced density of the intrahepatic biliary network compared to those in wild-type larvae. These data highlight the essential role of pkd1l1 in normal development and function of the zebrafish biliary system, supporting a role for this gene as a cause of BASM.

Liver-restricted deletion of the biliary atresia candidate gene Pkd1l1 causes bile duct dysmorphogenesis and ciliopathy.

A recent multicenter genetic exploration of the biliary atresia splenic malformation syndrome identified mutations in the ciliary gene PKD1L1 as candidate etiologic contributors. We hypothesized that deletion of Pkd1l1 in developing hepatoblasts would lead to cholangiopathy in mice. CRISPR-based genome editing inserted loxP sites flanking exon 8 of the murine Pkd1l1 gene. Pkd1l1Fl/Fl cross-bred with alpha-fetoprotein-Cre expressing mice to generate a liver-specific intrahepatic Pkd1l1 -deficient model (LKO). From embryonic day 18 through week 30, control ( Fl/Fl ) and LKO mice were evaluated with standard serum chemistries and liver histology. At select ages, tissues were analyzed using RNA sequencing, immunofluorescence, and electron microscopy with a focus on biliary structures, peribiliary inflammation, and fibrosis. Bile duct ligation for 5 days of Fl/Fl and LKO mice was followed by standard serum and liver analytics. Histological analyses from perinatal ages revealed delayed biliary maturation and reduced primary cilia, with progressive cholangiocyte proliferation, peribiliary fibroinflammation, and arterial hypertrophy evident in 7- to 16-week-old LKO versus Fl/Fl livers. Following bile duct ligation, cholangiocyte proliferation, peribiliary fibroinflammation, and necrosis were increased in LKO compared with Fl/Fl livers. Bile duct ligation of the Pkd1l1 -deficient mouse model mirrors several aspects of the intrahepatic pathophysiology of biliary atresia in humans including bile duct dysmorphogenesis, peribiliary fibroinflammation, hepatic arteriopathy, and ciliopathy. This first genetically linked model of biliary atresia, the Pkd1l1 LKO mouse, may allow researchers a means to develop a deeper understanding of the pathophysiology of this serious and perplexing disorder, including the opportunity to identify rational therapeutic targets.

Случай успешного лечения пациента с аневризмой селезеночной артерии, мальформацией селезеночной вены и спленомегалией

The clinical picture, diagnosis and selected option of surgical treatment of splenic artery aneurysm with splenic vein malformation and splenomegaly in a 30-year-old patient are discussed.

Biliary atresia & choledochal malformation–—Embryological and anatomical considerations

The two main biliary pathologies in paediatric practice, biliary atresia and choledochal malformations (CM), have their origins within prenatal life. Nevertheless, the actual mechanisms remain elusive with many unanswered questions. The extrahepatic bile duct develops as a funnel-like structure emerging from the foregut from about 3-4 weeks of gestation into the mesenchyme of the septum transversum. The cranial elements of this contain hepatoblasts - the precursors to the two key cell lines that will become hepatocytes and biliary epithelial cells. The intrahepatic bile ducts develop separately and emerge from a complex process involving the ductal plate surrounding the in-growing portal venous system from about the 7-8th week of gestation.A developmental defect at some point(s) in this process may be the cause of at least some variants of BA - the Biliary Atresia Splenic Malformation syndrome particularly - though evidence in the more common isolated BA is much more circumstantial. Similarly, some types of choledochal malformation, specifically the cystic type of CM, are invariably present during prenatal life although again an actual aetiological mechanism remains elusive.

Rare spontaneous monochorionic dizygotic twins: a case report and a systematic review

BackgroundMonochorionic dizygotic twins are a rare condition, mostly related to assisted reproductive technology. This type of twinning is burdened by the same risk of pregnancy complications found in monochorionic monozygotic pregnancies.Case presentationWe report a case of spontaneous monochorionic dizygotic twins sharing situs inversus abdominalis and isolated levocardia, with only one twin affected by biliary atresia with splenic malformation syndrome. We also conducted a literature review of the 14 available documented monochorionic dizygotic twin gestations spontaneously conceived.ConclusionsIt is still unclear how this unusual type of twinning can occur in spontaneous conception. The evidence so far suggest the importance to timely diagnose the chorionicity, in order to adequately manage the typical complications associated with monochorionicity.

Outcomes of biliary atresia splenic malformation (BASM) syndrome following Kasai operation: a systematic review and meta-analysis.

Outcomes of biliary atresia splenic malformation (BASM) syndrome following Kasai operation: a systematic review and meta-analysis.

Difficulty in the Diagnosis of Biliary Atresia Splenic Malformation Syndrome In Utero.

The fetus of a 30-year-old pregnant Japanese woman was diagnosed with absence of inferior vena cava (IVC) and azygos continuation of interrupted IVC without cardiac anomalies at 34 weeks of gestation, and a healthy male neonate weighing 2,910 g was delivered at 37 weeks of gestation. On day 42 after birth, direct bilirubin predominant hyperbilirubinemia and high serum gamma-GTP levels were detected. Computed tomography revealed the presence of a lobulated and accessory spleen, and laparotomy demonstrated type III biliary atresia (BA), confirming the final diagnosis of BA splenic malformation (BASM) syndrome. In retrospect, non-visualization of the gallbladder was missed in utero. The combination of the absence of IVC and BA without cardiac anomalies is far less likely to occur in left isomerism. Although BA remains difficult to detect in utero, special attention should be paid to cases of BA associated with findings of left isomerism, including the absence of IVC, to enable early diagnosis and treatment of BASM.

Biliary Atresia: Clinical Phenotypes and Aetiological Heterogeneity.

Biliary atresia (BA) is an obliterative condition of the biliary tract that presents with persistent jaundice and pale stools typically in the first few weeks of life. While this phenotypic signature may be broadly similar by the time of presentation, it is likely that this is only the final common pathway with a number of possible preceding causative factors and disparate pathogenic mechanisms—i.e., aetiological heterogeneity. Certainly, there are distinguishable variants which suggest a higher degree of aetiological homogeneity such as the syndromic variants of biliary atresia splenic malformation or cat-eye syndrome, which implicate an early developmental mechanism. In others, the presence of synchronous viral infection also make this plausible as an aetiological agent though it is likely that disease onset is from the perinatal period. In the majority of cases, currently termed isolated BA, there are still too few clues as to aetiology or indeed pathogenesis.

Recurrent Epistaxis and Diffuse Hepatic and Splenic Vascular Malformations

Question: A 48-year-old man was admitted to emergency department because of left upper abdominal pain for 3 weeks and yellow urine for 1 week. The patient was diagnosed with splenic hemangioma for 3 years and recurrent epistaxis for 5 years, without further treatment. Physical examination showed tenderness and rebound pain in the left upper abdomen, no muscle tension, with shifting dullness. Laboratory studies showed a neutrophil count of 8990/mm3 (reference range, 1900–8000/mm3), a hemoglobin level of 66 g/L (reference range, 131–172 g/L), a total bilirubin level of 57.23 μmol/L (reference range, 5.1–20 μmol/L), a serum alanine aminotransferase level of 302.9 U/L (reference range, 9–50 U/L), a serum aspartate aminotransferase level of 117.5 U/L (reference range, 15–40 U/L), an activated partial prothrombin time of 34.6 (reference range, 25–34), and a quantitative D-dimer level of 361.23 (reference range, 0–0.55). Emergency abdominal computed tomography scan showed diffuse hepatic and splenic vascular malformations (Figure A), and a ruptured splenic tumor (Figure B, arrow). It is worth noting that the patient's father had the same disease during his lifetime after asking about the family history. What is the most likely diagnosis? Look on page 808 for the answer and see the Gastroenterology website (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and images in GI. After consultation with the patient, he underwent emergency splenectomy and liver biopsy. Histopathology demonstrated the dilatation of hepatic capillaries, showing hemangioma-like changes (Figure C). The ruptured splenic tumor was confirmed pathologically as hemangioendothelioma. After a multidisciplinary consultation, the patient was diagnosed with hereditary hemorrhagic telangiectasia (HHT) according to the Curaçao criteria.1Faughnan M.E. Palda V.A. Garcia-Tsao G. et al.International guidelines for the diagnosis and management of hereditary haemorrhagic telangiectasia.J Med Genet. 2011; 48: 73-87Crossref PubMed Scopus (745) Google Scholar HHT, also called Osler–Weber–Rendu disease, is an autosomal-dominant disease. Up to one-third of patients have hepatic involvement and manifest as vascular malformations,2Chung D.Y. Federle M.P. Barrett J.P. et al.Hepatic hereditary hemorrhagic telangiectasia.Clin Gastroenterol Hepatol. 2006; 4 (xx)Abstract Full Text Full Text PDF Scopus (1) Google Scholar such as hepatic arteriovenous fistula (Figure D, rectangle). Martini3Martini G.A. The liver in hereditary haemorrhagic teleangiectasia: an inborn error of vascular structure with multiple manifestations: a reappraisal.Gut. 1978; 19: 531-537Crossref PubMed Scopus (95) Google Scholar classified patients with hepatic disease due to HHT into 3 subgroups: patients who had telangiectases with fibrosis or cirrhosis (as in our case), those who had cirrhosis without telangiectases, and those who had telangiectases without fibrosis or cirrhosis. Treatment is mostly supportive, but severe patients may require hepatic artery embolization or liver transplantation.2Chung D.Y. Federle M.P. Barrett J.P. et al.Hepatic hereditary hemorrhagic telangiectasia.Clin Gastroenterol Hepatol. 2006; 4 (xx)Abstract Full Text Full Text PDF Scopus (1) Google Scholar During the period of waiting for liver transplantation, the patient developed hepatic and renal insufficiency and respiratory failure. On day 11 of hospitalization, the patient's family asked to be transferred back to the local hospital for treatment. The patient died of multiple organ failure on the third day after transfer.

Torsion of the Vascular Pedicle of A Wandering Spleen: An Unusual Cause of Intestinal Strangulation

Ectopic spleen is a rare splenic malformation. Apart from torsion of the vascular pedicle, a common complication, an ectopic spleen could be responsible of an acute intestinal obstruction. We report a case of an 8-year-old girl who presented an acute abdomen, following of the transverse colon strangulation by the torsion of the vascular pedicle of a wandering spleen. The patients benefited a surgical opening into the abdomen who has been confirmed the diagnosis and made a detorsion of the vascular pedicle of spleen with splenopexy.The interest of this case report lies on the rarity of a wandering spleen and on the unusual situation of transverse colon strangulation by the vascular pedicle of spleen.

Unusual Clinical Course for Untreated Malformative Biliary Atresia Infant: Is Portal Hypertension an Important Driver of Liver Fibrosis?

In biliary atresia, infants left untreated, and in those with unsuccessful porto-enterostomy, hepatic condition and function worsen rapidly towards cirrhosis, malnutrition, portal hypertension with ascites, and variceal haemorrhage; many die within the first 3 years of life unless they benefit from liver replacement. We describe a girl with biliary atresia splenic malformation syndrome, who had portal vein cavernoma and microsplenia; she did not undergo porto-enterostomy. She survived with her native liver over the age of 3 years. Remarkably, she remained in satisfactory condition in absence of ascites or severe hepatic dysfunction, when 4 other similar patients-managed during the same period of time-all had the usual clinical deterioration and ascites, with the need for liver replacement. To our knowledge, there is no similar report in literature. Possible pathogenetic mechanisms and the role of portal hypertension as important factors are discussed.

Antenatal diagnosis of biliary atresia: a narrative review

Background and Objective: Biliary atresia (BA) is a rare obliterative disease of the extra- and intrahepatic biliary tree that represents the leading indication for liver transplantation in childhood, accounting for about 50% of transplants in children and about 10% of transplants at any age. This disease usually presents as persistent jaundice and acholic stools beyond the first few weeks of life. Nevertheless, 10–15% of patients present a developmental and truly innate disease in origin, showing either congenital anomalies (such as those in BA splenic malformation syndrome, BASMs) or cystic dilatation of the extrahepatic biliary tract that takes origin in early embryogenic life. The evidence on antenatal diagnosis of BA is poor and only few case reports and case series reported the impact of prenatal assessment on post-surgical outcome.

Cardiac-associated biliary atresia (CABA): a prognostic subgroup

ObjectivesTo describe the range of concurrent cardiac malformations in biliary atresia (BA) while providing a functional framework of risk.MethodsDemographic and variables were collected from a prospectively maintained single-centre database. Infants...

Postraumatic Torsion of Wandering Spleen in 9-year-old Boy

Post-traumatic torsion of wondering spleen is extremely rare cause of acute abdominal pain in children with only few cases reported. We report a case of a 9-year-old boy with wandering spleen torsion after bike crash and subacute clinical presentation. After a bicycle crash and a period of persistent fever family physician performed an ultrasound of abdomen which showed a round focal lesion of 10 x 12 cm in size, a spleen-like echogenicity in the middle-lower abdominal position and in the small pelvis, which raised suspicion of ectopic (wandering) spleen. The abdominal MSCT confirmed the diagnosis of wandering spleen, Numerous immunologic, hematological, radiological, infectious, endocrinological, chromosomal and cytological tests and markers confirmed a diagnosis of the splenic malformation. A surgeon arranged to perform splenopexy after checking the vaccination status. Laparotomy was initiated. The splenic artery and vein, which was in a triple twist, was released and due to the resulting path, the spleen itself was larger than the CT finding. The spleen was placed under the left ribs and splenopexy was performed. At the fifteen-day and two-month follow ups, the patient felt good, was painless, afebrile and the spleen gradually decreased. Wondering spleen should be considered as a possible cause of acute abdominal pain when the spleen is not seen in its usual position. The treatment of choice is surgery, with the goal of preservation of the organ whenever possible.

Biliary Atresia in Northwest Iran: Epidemiologic Features and Long-Term Outcome

Background: Biliary atresia is a rare distractive cholangiopathy in childhood and the most common cause of liver transplantation in pediatrics. Present study is the first report of biliary atresia and its incidence and outcome from northwest of Iran. Methods: In this retrospective cohort study, all patients with biliary atresia admitted to the Tabriz Children’s Hospital from March 2006 to March 2016were included. Demographical, clinical and preclinical data of all patients are extracted from the hospital records. Information about the outcome after Kasai portoenterostomy was gathered by reviewing the progress notes or by phone call from the parents. The Mann-Whitney U and chi-square or Fisher’s exact tests were used for comparison of continuous and categorical variables respectively. Survival curves and tables, Kaplan-Meier method and Cox regression were used for survival analysis. Results: The incidence rate of biliary atresia was 1/13280 live births. Isolated form of biliary atresia was seen in 85.1% of cases. Splenic malformation was not observed in our patients. The rate of successful Kasai Portoenterostomy was 42.9%. Survival analysis showed that 1, 2, 3, 5, and 10-year native liver survival rate was 73%, 56%, 54%, 40% and 31%, respectively. Median overall survival rate was 36 months [95%CI: 2.89 - 69.1]. Successful Kasai Portoenterostomy and clearance of jaundice was the only factor that affected survival rate. Conclusions: The incidence rate of biliary atresia in Northwest of Iran was lower than that in other Asian countries. Like other Asian countries, spleen anomaly was rare in our patients. The success of Kasai Portoenterostomy and survival rates of our cases were lower than that in other Asian countries.

Biliary Atresia Splenic Malformation Syndrome: A Single Center Experience

Abstract:
 Introduction: The cause of biliary atresia (BA) is not understood exactly as well as biliary atresia splenic malformation (BASM) syndrome. BA is destructive biliary fibrosis; the etiology may be multifactorial. Association of cytomegalovirus (CMV) and BA have been shown in many reports but CMV and BASM have not been mentioned in the literature. So we aimed to report BASM experiences, an association of CMV infection and need of duodenoduodenostomy if preduodenal portal vein exists.
 Materials and Methods: The data were collected retrospectively from Cukurova University which is one of the largest tertiary hospitals in Turkey between 2005-2017. The patients of sex, age, blood chemistry counts, TORCH infections blood parameters, BA types, operational findings and mortality were noted.
 Results: In total, 59 BA patients were diagnosed between 2005- 2017. Seven of them were classified as BASM. The median age of them was 60 days (45-90 days). Three of them were girl and 4 of them were male in gender. The main complaint of whole patients was jaundice. The jaundice of 6 patients began since birth. One of them began at 20 days-age. Median total / direct blood bilirubin levels were 9.6 / 5.4 mg/dl. Median values of liver function tests; ALT, AST and GGT were 77 IU/L, 201 IU/L and 607 IU/L respectively.
 Five of the patients showed positive results for anti-CMV immunoglobulin M. All had positive anti-CMV Ig G and anti-toxoplasmosis Ig G.
 Evaluation of the types of BA revealed that one patient had type 2, while all others had type 3. Four of BASM patients had polysplenia and one had asplenia. Five of them had a preduodenal portal vein. All of them had midgut malrotation. One had inferior vena cava interruption. One had hepatic artery anomaly which was originated from SMA.
 The median time of follow-up was 4 years (1-5 years). All of them are alive and 1 required liver transplantation.
 Conclusion: BASM should be kept in mind by the surgeon for the requirement of additional surgical procedures such as Ladd procedure, duodenoduodenostomy with Kasai Porto-enterostomy.
 Duodenoduodenostomy may be performed when the existence of preduodenal portal vein.
 Further research is recommended for CMV infection and BASM.

Identification of Polycystic Kidney Disease 1 Like 1 Gene Variants in Children With Biliary Atresia Splenic Malformation Syndrome.

Biliary atresia (BA) is the most common cause of end-stage liver disease in children and the primary indication for pediatric liver transplantation, yet underlying etiologies remain unknown. Approximately 10% of infants affected by BA exhibit various laterality defects (heterotaxy) including splenic abnormalities and complex cardiac malformations-a distinctive subgroup commonly referred to as the biliary atresia splenic malformation (BASM) syndrome. We hypothesized that genetic factors linking laterality features with the etiopathogenesis of BA in BASM patients could be identified through whole-exome sequencing (WES) of an affected cohort. DNA specimens from 67 BASM subjects, including 58 patient-parent trios, from the National Institute of Diabetes and Digestive and Kidney Diseases-supported Childhood Liver Disease Research Network (ChiLDReN) underwent WES. Candidate gene variants derived from a prespecified set of 2,016 genes associated with ciliary dysgenesis and/or dysfunction or cholestasis were prioritized according to pathogenicity, population frequency, and mode of inheritance. Five BASM subjects harbored rare and potentially deleterious biallelic variants in polycystic kidney disease 1 like 1 (PKD1L1), a gene associated with ciliary calcium signaling and embryonic laterality determination in fish, mice, and humans. Heterozygous PKD1L1 variants were found in 3 additional subjects. Immunohistochemical analysis of liver from the one BASM subject available revealed decreased PKD1L1 expression in bile duct epithelium when compared to normal livers and livers affected by other noncholestatic diseases. Conclusion: WES identified biallelic and heterozygous PKD1L1 variants of interest in 8 BASM subjects from the ChiLDReN data set; the dual roles for PKD1L1 in laterality determination and ciliary function suggest that PKD1L1 is a biologically plausible, cholangiocyte-expressed candidate gene for the BASM syndrome.

Biliary atresia and liver transplantation: results and thoughts for primary liver transplantation in select patients.

Biliary atresia (BA) is one of the most common indications for liver transplantation in children. Despite advances in biliary atresia surgical techniques, most children will ultimately require liver transplantation. Possible pre-operative predictors of outcome after the Kasai operation are: 1. Age at operation 2. Presence of the biliary atresia splenic malformation syndrome (BASM) 3. Center specific factors 4. Liver histology and 5. Anatomic pattern of bile ducts found at surgery.Age at surgery is considered a strong predictor of success after portoenterostomy. In a recent study, age of 75 days or more at surgery was associated with less frequent resolution of jaundice and decreased transplant free survival. Similarly, the Ohi type II or III anatomy was associated with a higher risk of transplantation or death than type I. Inflammatory findings on pre-operative biopsy predicted a pooreroutcome after a Kasai procedure than obstructive changes. Nodularity of the liver at surgery as well as ascites was associated with a poorer prognosis.Primary transplantation is rarely done despite excellent outcome. Deaths on the waiting list also have improved with routine use of split and live donor transplantation. The Kasai operation has the highest failure rate in its stated objective than any other operation in pediatric surgery. Failure to achieve any improvement in jaundice occurs in over 30% of all cases, even in the best of hands, and transplantation or listing for transplantation occurs in over half the children with type II and III BA by one year of age in countries where liver transplantation is readily available.There are almost no studies in children with BA that compare the outcome after liver transplantation for BA with or without a prior Kasai procedure. It is postulated that a prospective trial in children predicted to have a poor prognosis after the Kasai procedure based on anatomic pattern, liver histology and presence of BASM, would yield improved care, spare some infants needless surgery, and quite possibly result in diminished morbidity and mortality following liver transplant.

Choledochal cyst, polysplenia and situs ambiguous: A rare and new association

Abstract Introduction Situs ambiguous (SA) is a rare clinical entity that includes a spectrum of abnormalities in which organs and vessels are opposed to their normal arrangement. SA is frequently associated with other malformations such as splenic alterations, biliary atresia and vascular abnormalities. We report two cases of patients with SA, polysplenia and choledochal cyst. This association has never been described to date. Case reports Two patients, both males, came to our attention at the ages of 7 and 8 months after ultrasound identification of choledochal cysts. One patient, who had a prenatal suspicion of situs ambiguous and dextrocardia, presented with failure to thrive and increased hepatic enzymes. The other patient was asymptomatic, but prenatal evaluation showed gastric malposition. Post-natal laboratory tests were normal. Preoperative radiological diagnostic work-up showed polysplenia, intestinal anomaly of rotation and fixation, pre-duodenal portal vein in one baby. Both patients underwent surgical correction by cyst excision and Roux-en-Y hepaticojejunostomy. Follow-up (3 months and 3.5 years respectively) was uneventful. Biochemical hepatic parameters normalized soon after surgery. Discussion Situs anomalies in children are often associated with other malformations. The most common are splenic and cardiac defects but intestinal malformations and hepatico-biliary abnormalities have been reported too. Above all, the BASM (biliary atresia splenic malformation) syndrome has been extensively examined, obtaining important information on the etiology of the cystic form of biliary atresia. Conclusions A careful evaluation of patients with situs ambiguous is important to exclude associated anomalies and to plan the most appropriate surgical approach. The association with choledochal cyst should be taken into account.