Propranolol and infantile hemangiomas: Outcome from a tricentric study.

INTRODUCTION: The introduction of propranolol as systemic therapy for infantile hemangiomas (IH) has changed the natural history of these tumors. Cases presenting with ulceration, functional limitation, and visceral or life-threatening localization are excellent indications to medical therapy. The aim was to report the medium term follow-up after the introduction of propranolol in 3 referral centers with particular attention to outcome and surgical treatments. MATERIALS AND METHODS: In the period 2011-2018 348 patients underwent systemic therapy with propanolol at a mean age of 3.5 months (range 1-10). The indications to begin the treatment were: visceral localization (10,6%), ulceration (20%), risk of severe esthetic impairment (27%), and peri­orifices localization (42.4%). RESULTS: The minimum follow-up was 1 year. Propranolol was administered for a mean of 11 months (range: 6-19) and in 22 cases it was resumed for extra 4.5 months due to rebound. Overall, 97.4% responded to therapy without severe side effects. Seven patients underwent surgery and 9 laser therapy . Twenty-four cases are scheduled for surgery for evident inesthetisms and 4 will undergo laser therapy to complete the treatment. CONCLUSIONS: The use of propranolol has considerably decreased the surgical indications for IH, improved the esthetic and functional outcome, and simplified the definitive surgical treatment. The response rate to therapy is very high and in case of failure both laser and surgery are still very effective. The correct diagnosis, early starting, and adequate duration of therapy are key factors for the success of treatment.

Talking about sexuality with your own child. The perspective of the parents of children born with arm.

PURPOSE: Evaluate whether parents have ever discussed sexuality with their children with anorectal malformations (ARM), which sexuality issues they think should be addressed and who, in their opinion, should address these issues. METHODS: Parents from the Italian Parents' and Patients' Association for Anorectal Malformation participated in meetings organized by the Association together with local Pediatric Surgical Units and were asked to fill in a questionnaire. RESULTS: 103 parents participated. Overall, 66% of parents had never talked about sex with their children. Children's age was marginally correlated with occasions to talk about sexuality (r = .202, p = 0.53) indicating that the older were the children, the more the parents talked about sexuality. The majority of parents reported that their children should have the possibility to talk about sex with them (72%), psychologists (57%), gynecologists/andrologists (47%), pediatric surgeons (33.5%), surgeons specialized in ARM (39.8%), friends (28%), nurses (24.7%) and teachers (20.4%), respectively. The most important topic they thought their children should address was handling serene sexuality, although the most common topic effectively discussed with them was the conception. CONCLUSION: Psychologists, gynecologists/andrologists, and pediatric surgeons are seen as key resources for talking about sexuality. A great number of parents express the wish that their children had more opportunities to discuss sexual topics with pediatric surgeons.

The use of biological membranes for correction of congenital malformations.

Many congenital malformations often require a multidisciplinary and multistep surgical treatment, including the use of biological membranes. Aims of the study were to describe the use of these membranes for the correction of malformations, their clinical performance at follow-up, and patient's tolerance to them. The study included patients treated between 2009 and November 2020 in two referral centers. They were affected by abdominal wall defects (AWD), esophageal atresia/tracheo-esophageal fistula (EA/TEF), diaphragmatic hernia (CDH), spinal defects (SD), and anorectal malformations (ARM). The human origin membranes used during surgery were amniotic membrane, fascia lata, and pericardium provided by the local tissue bank and the porcine-derived membrane available on the market. Thirty-one patients were retrieved. The sample included 10 AWD, 7 EA/TEF, 5 CDH, 4 SD, 2 ARM, and 3 miscellaneous defects. The median age at repair was 139 days (range: 10,5-1494). The median follow-up was 1021 days (range: 485,5-1535). Two patients were lost at follow-up. The defects were successfully repaired and the membranes perfectly tolerated in 28/29 cases. In 1 case of CDH the fascia lata was replaced with a Goretex patch due to recurrence of the defect. This is the largest series on the use of biological membranes in congenital malformations. The variety of tissues allows to choose the best material for each malformation. The excellent tolerance and performance of this first series of patients encourage the use of these membranes to correct different type of malformations at any age.

The impact of perioperative care on complications and short term outcome in ARM type rectovestibular fistula: An ARM-Net consortium study.

BACKGROUND: The impact of perioperative care interventions on postreconstructive complications and short-term colorectal outcome in patients with anorectal malformation (ARM) type rectovestibular fistula is unknown. METHODS: An ARM-Net consortium multicenter retrospective cohort study was performed including 165 patients with a rectovestibular fistula. Patient characteristics, perioperative care interventions, timing of reconstruction, postreconstructive complications and the colorectal outcome at one year of follow-up were registered. RESULTS: Overall complications were seen in 26.8% of the patients, of which 41% were regarded major. Differences in presence of enterostomy, timing of reconstruction, mechanical bowel preparation, antibiotic prophylaxis and postoperative feeding regimen had no impact on the occurrence of overall complications. However, mechanical bowel preparation, antibiotic prophylaxis ≥48 h and postoperative nil by mouth showed a significant reduction in major complications. The lowest rate of major complications was found in the group having these three interventions combined (5.9%). Multivariate analyses did not show independent significant results of any of the perioperative care interventions owing to center-specific combinations. At one year follow-up, half of the patients experienced constipation and this was significantly higher among those with preoperative mechanical bowel preparation. CONCLUSIONS: Differences in perioperative care interventions do not seem to impact the incidence of overall complications in a large cohort of European rectovestibular fistula-patients. Mechanical bowel preparation, antibiotic prophylaxis ≥48 h, and postoperative nil by mouth showed the least major complications. Independency could not be established owing to center-specific combinations of interventions. TYPE OF STUDY: Treatment study. LEVEL OF EVIDENCE: III.

Short versus mid-long-term outcome of transanal irrigation in children with spina bifida and anorectal malformations.

PURPOSE: We assessed short- and mid-long-term clinical efficacy of transanal irrigation (TAI) and its effect on the quality of life of children with spina bifida (SB) and anorectal malformations (ARM). METHODS: Seventy-four pediatric patients (age 6-17 years) with SB and ARM with neurogenic bowel dysfunction were enrolled for a prospective and multicentric study. Patients were evaluated before the beginning of TAI (T0), after 3 months (T1) and after at least 2 years (range 24-32 months) (T2) using a questionnaire assessing bowel function, the Bristol scale, and two validated questionnaires on quality of life: the CHQ-PF50 questionnaire for the parents of patients aged 6-11 years and the SF36 questionnaires for patients aged between 12 and 18 years. RESULTS: Seventy-two patients completed TAI program in T1, and 67 continued into T2. Bowel outcomes (constipation and fecal incontinence) improved in both the SB and the ARM groups in the short and mid-long term. In both groups at T1 and T2, parents and children reported an improvement in quality of life and there was a significant increase of stool form types 4 and 5 as described by the Bristol scale. Common adverse effects during the study were similar at T1 and T2 without serious complications. CONCLUSIONS: We observed a sustained improvement in bowel management and quality of life in SB and ARM children during the study, more significant in the short term than in mid-long term. To maintain success rates in the mid-long term and to reduce the dropout rate, we propose patient training and careful follow-ups.

Tethered cord in patients affected by anorectal malformations: a survey from the ARM-Net Consortium.

PURPOSE: The goal of this study was to determine the degree of consensus in the management of spinal cord tethering (TC) in patients with anorectal malformation (ARM) in a large cohort of European pediatric centers. METHODS: A survey was sent to pediatric surgeons (one per center) members of the ARM-Net Consortium. RESULTS: Twenty-four (86%) from ten different countries completed the survey. Overall prevalence of TC was: 21% unknown, 46% below 15, and 29% between 15 and 30%. Ninety-six agreed on screening all patients for TC regardless the type of ARM and 79% start screening at birth. Responses varied in TC definition and diagnostic tools. Fifty percent of respondents prefer ultrasound (US), 21% indicate either US or magnetic resonance (MRI) based on a pre-defined risk of presenting TC, and 21% perform both. Discrepancy exists in complementary test: 82% carry out urodynamic studies (UDS) and only 37% perform somatosensory-evoked potentials (SSEP). Prophylactic untethering is performed in only two centers (8%). CONCLUSIONS: Survey results support TC screening in all patients with ARM and conservative management of TC. There is discrepancy in the definition of TC, screening tools, and complementary test. Protocols should be developed to avoid such variability in management.

Rectal adenocarcinoma in patients with anorectal malformations: report of two cases and a review of the literature.

AIM: Anorectal malformation (ARM) is a rare congenital disorder of the anus and rectum. In the last 30 years virtually all patients born with ARM have survived and surgeons from adult care may be called to deal with new and long-term sequelae, including tumors of the pulled-through anorectum. Two new cases of colorectal carcinoma in young adults born with ARM and a review of the literature is reported to emphasize the importance of a multidisciplinary follow-up. METHODS: A man and a woman, with previous history of ARM, presented at 34 years of age with symptoms of intestinal occlusion and a large pelvic mass. Both patients had no familial history of colorectal carcinoma. RESULTS: The patients underwent biopsies (mucinous rectal adenocarcinoma) and stadiation (T4N0M0). In one case the microsatellite instability showed a stable profile. Despite maximal treatments, including surgery, chemo- and radio-therapy, they both died a few years after diagnosis for progression of disease. CONCLUSION: Case studies are too limited to suggest guidelines for prevention and treatment of such complications, but the life-long follow-up is mandatory in the framework of a well-established network between pediatric and adult surgeons. The risk of tumor development in these patients should not be neglected and colleagues from adult care should be aware of the possibility this occurs in their practice.

Peristeen(®) transanal irrigation in paediatric patients with anorectal malformations and spinal cord lesions: a multicentre Italian study.

AIM: In paediatric and adult patients with neurogenic bowel, transanal irrigation (TAI) of the colon has gained popularity due to the introduction of a specifically designed device. The aim of this pilot study was to present the results of TAI using the Peristeen(®) TAI system in a group of paediatric patients with anorectal malformation (ARM) and congenital or acquired spinal cord lesions (SCLs). METHOD: Eight Italian paediatric surgery and spina bifida centres participated in the study. The inclusion criteria were age between 6 and 17 years, weight above 20 kg and unsatisfactory bowel management. Patients with chronic inflammatory bowel disease, mental disability and surgery within the previous 3 months were excluded. At the beginning of treatment (T0) and after 3 months (T1) the Bristol scale, a questionnaire assessing bowel function, and two questionnaires on quality of life (QoL) for patients aged 6-11 years (CHQ-pf50) and 12-17 years (SF36) were administered. RESULTS: Eighty-three patients were enrolled, and seventy-eight completed the study (41 ARMs, 37 SCLs). At T1, constipation was reduced in ARMs from 69% to 25.6% and in SCLs from 92.7% to 41.5%, faecal incontinence in ARMs from 50% to 18.6% and in SCLs from 39% to 9.8% and flatus incontinence in ARMs from 20.9% to 9.8% and in SCLs from 31.7% to 10%. At T0, the Bristol Stool Scale types were 1-2 in 45% of ARMs and 77.5% of SCL patients, whereas at T1 types 1-2 were recorded in only 2.5% of SCL patients. QoL improved in both groups. In the younger group, a significant improvement in QoL was recorded in ARM patients for eight of nine variables and in SCL patients for seven of nine variables. CONCLUSION: This study showed that Peristeen TAI resulted in a significant time reduction in colonic cleansing, increased independence from the carer and improved QoL in paediatric patients with ARMs and SCLs.

Towards the perfect ARM center: the European Union's criteria for centers of expertise and their implementation in the member states. A report from the ARM-Net.

BACKGROUND: Pediatric surgeons and patient organisations agree that fewer centers for anorectal malformations with larger patient numbers are essential to reach better treatment. The European Union transacts a political process which aims to realize such centers of expertise for a multitude of rare diseases. All the centers on a specific rare disease should constitute an ERN on that disease. ARM-Net members in different countries report on first experiences with the implementation of national directives, identifying opportunities and risks of this process. METHODS: Relevant details from the official European legislation were analyzed. A survey among the pediatric surgeons of the multidisciplinary ARM-Net consortium about national implementation was conducted. RESULTS: European legislation calls for multidisciplinary centers treating children with rare diseases, and proposes a multitude of quality criteria. The member states are called to allocate sufficient funding and to execute robust governance and oversight, applying clear methods for evaluation. Participation of the patient organisations is mandatory. The national implementations all over Europe differ a lot in respect of extent and timeframe. CONCLUSIONS: Establishing Centers of Expertise and a ERN for anorectal malformations offers great opportunities for patient care and research. Pediatric surgeons should be actively engaged in this process.

Congenital diaphragmatic hernia: focus on abnormal muscle formation.

BACKGROUND: CDH is a major birth defect, characterized by high mortality. How the initial defective mesenchymal substructures affects muscle malformation is unclear. Defects of genes involved in diaphragmatic development, such as friend-of-GATA2 (Fog2), may play an important role in its pathogenesis. We investigated the expression of Fog2 and proteins of myogenesis in a series of CDH and in diaphragms at different fetal ages, in order to clarify the role of muscular components during diaphragmatic development in cases with CDH. MATERIAL AND METHODS: Specimen were obtained from seven diaphragms of CDH cases undergoing surgery, 3 entire diaphragms from non repaired CDH, 5 control diaphragms at different gestational ages (16, 17, 22, 32, and 40g.w.), and 3 biopsy samples of normal voluntary muscle. The thickness of diaphragms at the edge of the defect in CDH and in developing diaphragms was measured. All samples were processed for HE staining and immunohistochemistry. Immunohistochemical expression of MyoD, Myf4, Pax7, Mib1 and Fog2 was evaluated. RESULTS: Mean thickness at the edge of the defect was 4.14mm. Contralateral hemi-diaphragm in 3 autopsies and in controls at 32 and 40weeks measured 2.25mm; histology showed a higher density of desmin-positive muscular cells at the edge of defect. CDH displayed scattered Myf4-positive cells (range 0%-10%, mean 2.4%), numerous Pax7-positive cells (range 0%-24%, mean 12.1%) and less than 1% Mib1-positive cells. Controls showed a reduction of positive cell with the progression of gestational age for Myf4 (30% at 16 weeks, 20% at 17 weeks, 5% at 22 weeks, 1% at 32 and 40 weeks), Pax7 (85% at 16 weeks and 17 weeks, 35% at 22 weeks, 11% at 32 weeks) and Mib1 (20% at 16 weeks, 8% at 17 weeks, 7% at 22weeks, 2% at 32 weeks). Fog-2 was diffusely positive in mesenchymal, mesothelial and muscular cells, in diaphragms from 16 to 22 weeks, decreasing to 20% of positive muscular cells in 32-week diaphragm. In CDH only mesothelial and mesenchymal cells were positive. Stem cell markers were negative in cases and controls. COMMENT: CDH shows a thick muscular border, with high number of mature muscle cells and significant increase of quiescent satellite cells (PAX7+, Mib1-). Abnormal architecture may affect the normal process of myogenesis and thus signaling and cell-cell interactions of myocytes. The expression of Fog2 in mesothelial and mesenchymal cells in CDH demonstrates the absence of a genetic defect involving Fog2 in our cases. Being Fog2 expressed in muscle cells at early stage supports the hypothesis that the altered diaphragmatic genesis may undermine also the muscular component instead of the only mesenchymal one.

European consensus meeting of ARM-Net members concerning diagnosis and early management of newborns with anorectal malformations.

The ARM-Net (anorectal malformation network) consortium held a consensus meeting in which the classification of ARM and preoperative workup were evaluated with the aim of improving monitoring of treatment and outcome. The Krickenbeck classification of ARM and preoperative workup suggested by Levitt and Peña, used as a template, were discussed, and a collaborative consensus was achieved. The Krickenbeck classification is appropriate in describing ARM for clinical use. The preoperative workup was slightly modified. In males with a visible fistula, no cross-table lateral X-ray is needed and an anoplasty or (mini-) posterior sagittal anorectoplasty can directly be performed. In females with a small vestibular fistula (Hegar size <5 mm), a primary repair or colostomy is recommended; the repair may be delayed if the fistula admits a Hegar size >5 mm, and in the meantime, gentle painless dilatations can be performed. In both male and female perineal fistula and either a low birth weight (<2,000 g) or severe associated congenital anomalies, prolonged preoperative painless dilatations might be indicated to decrease perioperative morbidity caused by general anesthesia. The Krickenbeck classification is appropriate in describing ARM for clinical use. Some minor modifications to the preoperative workup by Levitt and Peña have been introduced in order to refine terminology and establish a comprehensive preoperative workup.

Tethered cord in patients with anorectal malformation: preliminary results.

BACKGROUND: A tethered cord (TC) has been reported in as much as 50% of the patients affected by anorectal malformation (ARM). No guidelines for timing and modality of diagnosis and treatment have been established. We present the preliminary results of a multidisciplinary protocol carried out at our center. METHODS: Seventy-four ARM patients underwent spinal magnetic resonance imaging (MRI). All TC patients underwent videourodynamic (UD), somatosensory-evoked potentials (SEPs), and neurological examination at baseline and, if normal, at 5 and 10 years of age. Conversely, when UD or SEP abnormalities were detected the follow-up was individually tailored at shorter time. RESULTS: 25/74 patients had a neuroradiological TC (33.7%). Based on the results of UD, SEP, and neurological status, four patients were untethered, eight are possible candidates, nine are stable, and four were excluded because of incomplete data. DISCUSSION: Tethered cord is frequent in ARM patients. Because neurological deficits secondary to TC can contribute to neurological disability, we recommend routine MRI examination and a multidisciplinary program of follow-up in cases of TC. Preliminary results suggest the combined use of SEPs and UD could represent a useful adjunct to clinical examination in patients in whom a "wait and see" approach is preferred to the prophylactic surgery.

Early prenatal diagnosis of cloacal exstrophy with fetal magnetic resonance imaging.

Prenatal diagnosis of cloacal exstrophy can be challenging during pregnancy and, subsequently, the counseling very difficult. Available ultrasonographic criteria may be inadequate, especially in early gestational ages. A case of early prenatal detection of cloacal exstrophy with fetal magnetic resonance imaging is reported herein for the first time.

Gastroschisis in the rat model is associated with a delayed maturation of intestinal pacemaker cells and smooth muscle cells.

BACKGROUND: A pacemaker system is required for peristalsis generation. The interstitial cells of Cajal (ICC) are considered the intestinal pacemaker, and are identified by expression of the c-kit gene--encoded protein. Gastroschisis is characterized by a severe gastrointestinal dysmotility in newborns. In spite of this clinical picture, few studies have focused on smooth muscle cells (SMC) morphology and none on ICC. Therefore, their morphology has been studied in fetuses at term in the rat model of gastroschisis. METHODS: At 18.5 day's gestation (E18.5), 10 rat fetuses were killed, 10 underwent surgical creation of gastroschisis, and 10 underwent manipulation only. The small intestine of the latter 2 groups was harvested at E21.5. Specimens were processed for H&E, c-kit and actin (alpha smooth muscle antibody [alpha-SMA]) immunohistochemistry, and transmission electron microscopy (TEM). RESULTS: In the controls, SMC were c-kit+ and alpha-SMA+, with labeling intensity increasing by age. At E21.5, some cells around the Auerbach's plexus were more intensely c-kit+, and differentiating ICC were seen under TEM at this level. Gastroschisis fetuses had no c-kit+ cells referable to ICC. In the more damaged loops, SMC were very faintly c-kit+ and alpha-SMA+. Under TEM, there were few differentiated SMC and no presumptive ICC. In the less-damaged loops, SMC were faintly c-kit+ and alpha-SMA+ and had ultrastructural features intermediate between those of E18.5 and E21.5 controls; ICC were very immature. CONCLUSIONS: ICC and SMC differentiation is delayed in gastroschisis with the most damaged loops showing the most incomplete picture. These findings might help in understanding the delayed onset of peristalsis and the variable time-course of the recover seen in babies affected by gastroschisis.

[Ex utero intrapartum technique]. / La tecnica EXIT.

Upper airway obstruction of a neonate constitutes an emergency. The ex utero intrapartum technique (EXIT) is a procedure for safely managing airway obstruction at birth, in which placental support is maintained until the airway is evaluated and secured. The anaesthetist is involved in preventing uterine contractions that impair oxygenation of the foetus and cause placental separation, in providing foetal anaesthesia to help airway manipulations, in maintaining foetal pattern of circulation, in preventing and treating maternal hypotension and in resuscitating the neonate. General anaesthesia with high concentration of inhalational agents is preferred as it provides surgical tocolysis and foetal anaesthesia. Additional uterine relaxation may be obtained using tocolytic drugs like nitroglycerin or beta-adrenergic agonists. During EXIT the foetus is delivered only as far as the shoulders or thorax leaving the cord entirely in utero to maximize the duration of placental support and to minimize heat and water loss. In this position foetal airway is examined and secured, which may involve tracheal intubation, bronchoscopy or tracheostomy. The umbilical cord is divided and the neonate is completely delivered only after the airway has been secured. With EXIT, a potential life-threatening emergency at birth can be managed like an elective procedure that can improve the prognosis for foetuses with airway obstruction.

A new indication for buccal mucosal graft: isolated congenital fistula of the penile urethra.

Isolated congenital urethrocutaneous fistula is uncommon, and its repair has been associated with high incidence of recurrence. However, the use of buccal mucosal graft offers a satisfactory closure after previous failures. We report a new case in whom we adopted the buccal mucosal urethral replacement to treat the recurrence.

Neuronal differentiation and myenteric plexus organization are delayed in gastroschisis: an immunohistochemical study in a rat model.

Gastroschisis is a malformation due to prenatal rupture of the abdominal wall and evisceration of the midgut. Intestinal loops are shortened, matted, and covered by a peel caused by the harmful effect of the amniotic fluid. Babies born with gastroschisis suffer from gastrointestinal dysmotility. The present aim was to verify whether the myenteric plexus is damaged in a rat model of gastroschisis. In the gastroschisis rat model fetus, the myenteric plexus was not yet organized in the well-defined ganglia and, in the most damaged loops, the neuronal cells were scattered or absent. Immunohistochemistry for alpha-internexin and peripherin (markers of neuronal maturity) gave results similar to those of earlier embryonic ages. These findings indicate a delay in neuronal differentiation and myenteric plexus organization that might play a role in the postnatal dysmotility observed in gastroschisis.

EXIT procedure in a twin gestation and review of the literature.

Prenatal diagnosis can show masses of the fetal neck, mouth, and face that can potentially cause respiratory distress at birth. To prevent such an emergency, the EXIT (ex utero intrapartum technique) is performed: it is the intrapartum intubation of the fetus at term while still connected to the placenta. The EXIT procedure was first performed in a case of cervical teratoma. Up to now a total of 34 cases are described, mostly cervical teratomas (13 cases), lymphangiomas (7), epignathus (3); babies' outcome has been successful in 25 of them, with one death related to the procedure. Among the reported cases we are aware of only one where EXIT was performed in a twin gestation, in which the normal twin was delivered first. In our case the normal fetus was posterior to the twin with cervical malformation, requiring us to work on the latter while the former was still in the uterus. After having safely secured the airway in twin A, twin B was prompt delivered with excellent general conditions. Our limited experience enlarges the possibility to perform this prenatal procedure even in "nonstandard" conditions, such as a twin gestation, and may prove useful to those who are going to deal with such issues.

[The EX-utero Intrapartum Technique (EXIT) procedure in Italy]. / Il parto ex-utero intrapartum technique (EXIT) in Italia.

Aim of the study was to present the first two Italian cases of C-section performed with the EXIT procedure (EX-utero Intrapartum Technique). Deliveries were performed at the Division of Obstetrics and Gynecology of the Hospital of Padua in cooperation with the Pediatric Surgery Department, both tertiary care centers. The first case was a twin with a huge neck mass (cystic hygroma) and the second a fetus with an oropharyngeal mass (epignathus). Airway patency could have been compromised at birth in both of them. EXIT procedure consists in securing the airway of the fetus partially delivered and still connected with the placenta. This technique leaves an intact feto-placental circulation and guarantees a normal fetal oxygenation while fetal airway patency is secured. Both the fetuses were successfully intubated and the C-section ended up in a short period of time without maternal and fetal complications. The EXIT technique, performed for the first time in 1989 and now in many centers abroad, can be considered a safe procedure as long as a multidisciplinary approach is carried out. The EXIT procedure is indicated whenever fetal airways can be compromised at birth, that is when oropharyngeal masses, laryngeal atresia, cystic hygroma and goiter are encountered during prenatal ultrasound.

Congenital tracheobiliary fistula.

Congenital respiratory tract-biliary fistula, including tracheo- and broncho-biliary fistulae, are rare developmental anomalies. To date, only 18 cases have been reported. We present two additional cases that came to our attention after a long and difficult attempt to make a diagnosis. After surgical excision of the tract both children have remained symptom-free for 6 and 4 years, respectively. Bronchoscopy allows an early diagnosis, but patients also have to be investigated for associated biliary tree malformations.