Lost in transition? Loss of follow-up and quality of life in adults after resection of choledochal malformation in childhood.

Objectives: Choledochal malformation (CM) is a rare disease that can lead to malignancy and potential long-term sequelae despite surgical resection. There is no long-term follow-up data on patients after CM resection in Germany. We aimed to determine the long-term outcome of our patients with a duration of follow-up >10 years and focused on long-term sequelae and health-related quality of life (HRQOL). Methods: All patients who had undergone CM-resection in our department from 01/1978 to 06/2009 were contacted. Patients were interviewed about postoperative complications and their present medical attendance. HRQOL was determined using Pediatric Quality of Life Inventory 4.0 (PedsQL), version for adults. The PedsQL scales the HRQOL from 0 to 100, with higher scores indicating a better HRQOL. Scores were compared to those published for a healthy population. Results: Out of 56 patients who were contacted, 23 (41 %) participated. The median age at time of surgery was 3.1 years (6 days-16.1 years) and at time of the survey 24.3 years (11.1-53.8 years). Eighteen patients (78 %) had ceased their gastroenterologic follow-up at a median time of 4.3 years after surgery. Five (22 %) were still in gastroenterologic follow-up, two of these had an uneventful clinical course, and three (13 %) had ongoing complications attributed to the CM. One of these had undergone hemihepatectomy 34 years postoperatively due to bile duct stenosis, one had undergone removal of bile duct stones 14 years postoperatively, and one suffered from portal vein thrombosis with esophageal and jejunal varices. There was no mortality in our series. Median total HRQOL score was 89. There was no significant difference in the median total health, physical health, and psychosocial health scores of our patients in comparison to the healthy population. Conclusions: We confirmed that the majority of patients after CM resection are lost to follow-up. Those who answered our questionnaire showed a good HRQOL. Given the high rate of severe long-term complications and the life-long risk of malignancy, we recommend a transition program for all patients.

Antenatally Detected Choledochal Malformation: What Are We Waiting For?

INTRODUCTION: An increasing proportion of congenital choledochal malformation (CCM) are being detected on antenatal ultrasound. However, the actual timing of its surgical correction remains controversial with some series showing an excess of complications the earlier the operation. The aim of this study was to characterize the pathophysiological aspects of this cohort from the perspective of age at surgery in order to inform a more rational basis for clinical decision-making. METHODS: We analysed a prospective database of CCM acquired over a 26-year period (Jan. 1997 to Dec. 2022) for patient demography; details of pre- and post-natal imaging; age at surgical intervention; operative complications (Clavien-Dindo classification) and outcome. Data are quoted as median (IQR). All comparisons are non-parametric. A P value of 0.05 was accepted as significant. RESULTS: There were 58 (72% female) children with an antenatally-detected CCM from a total of 265 (21.8%) in the series. These were classified as Type 1C (n = 47; 81%), type 4C (n = 3; 5%) and Type 5 (n = 8; 14%). There were no Type 1F lesions in this cohort. Median age at surgery was 113 (IQR 57-198) days. Postnatal cyst (US) size varied from 12 to 130 mm but there was little evidence of a relationship between this and post-natal liver biochemistry (e.g. bilirubin rS = 0.01, P = 0.44; AST rS = 0.14, P = 0.19). Choledochal pressure measurements (n = 46) showed resting pressures of 12 (9-21) mmHg with no significant correlation with age (P = 0.4) or aspartate aminotransferase (P = 0.2) or γ-glutamyl transferase (P = 0.06). The cohort was divided into 2 groups (Early and Late) based on the median age at surgery (all open) (113 days). Biliary obstruction was more common in the Early group (10 vs. 2; P = 0.01). Two perforations occurred, both in the Early group. With a deliberate policy of regular ultrasound-based follow-up we have seen no anastomotic complications (leak, stenosis, persistent intrahepatic biliary dilatation or stones) or post-operative cholangitis in any child [median follow-up 3.42 (1.30-8.05) years]. CONCLUSIONS: This is one of the largest series documenting the outcomes of antenatally-detected CCMs, certainly in Europe and North America. Such lesions are invariably cystic in nature, and either Types 1C, 4C or 5. The absence of complications using a policy of early intervention (where possible) in experienced hepatobiliary units was shown. EVIDENCE LEVEL: II.

Long-term outcome for children undergoing open hepatico-jejunostomy for choledochal malformations: a 43-year single-center experience.

PURPOSE: To report on our 43-year single-center experience with children operated on for Choledochal Malformations (CMs), focusing on long-term results and Quality of life (QoL). MATERIALS AND METHODS: All consecutive pediatric patients with CMs who underwent surgical treatment at our center between October 1980 and December 2022 were enrolled in this retrospective study. We focused on long-term postoperative complications (POCs), considered to be complications arising at least 5 years after surgery. We analyzed QoL status once patients reached adulthood, comparing the results with a control group of the same age and sex. RESULTS: One hundred and thirteen patients underwent open excision of CMs with a Roux-en-Y hepaticojejunostomy (HJ). The median follow-up was 8.95 years (IQR: 3.74-24.41). Major long-term POCs occurred in six patients (8.9%), with a median presentation of 11 years after surgery. The oldest patient is currently 51. No cases of biliary malignancy were detected. The QoL of our patients was comparable with the control group. CONCLUSION: Our experience suggests that open complete excision of CMs with HJ achieves excellent results in terms of long-term postoperative outcomes. However, since the most severe complications can occur many years after surgery, international cooperation is advisable to define a precise transitional care follow-up protocol.

Controversies in Choledochal Malformation in Children: An International Survey among Pediatric Hepatobiliary Surgeons and Gastroenterologists.

BACKGROUND: While congenital choledochal malformation (CCM) is relatively well known within the pediatric surgical and pediatric gastroenterological communities, many controversies and questions remain. METHODS: In this paper, we will discuss the results of an international Delphi survey among members of the European Reference Network RARE-LIVER and of the faculty of the Biliary Atresia and Related Diseases (BARD) network to identify the most common practices as well as controversies regarding diagnosis, treatment and follow-up of this still enigmatic disease. RESULTS: Twenty-two individual respondents completed the survey. While there seems to be agreement on the definitions of CCM, preoperative workup, surgical approach and follow-up still vary considerably. The mainstay of treatment remains the removal of the entire extrahepatic biliary tract, clearance of debris both proximally and distally, followed by reconstruction with (according to 86% of respondents) a Roux-en-Y hepaticojejunostomy. Nonetheless, both laparoscopic and robotic-assisted resections are gaining ground with the suggestion that this might be facilitated by concentration of care and resources in specialized centers. However, long-term outcomes are still lacking. CONCLUSIONS: As even post-surgical CCM has to be considered as having premalignant potential, follow-up should be well-organized and continued into adulthood. This seems to be lacking in many centers. International cooperation for both benchmarking and research is paramount to improving care for this rare disease.

[Comparative analysis of the bile duct reconstruction methods in children with choledochal malformation]. / Sravnitel'nyi analiz sposobov rekonstruktsii zhelchnykh khodov pri mal'formatsii obshchego zhelchnogo protoka u detei.

OBJECTIVE: To compare various methods of bile duct reconstruction in children with choledochal malformation (CM). MATERIAL AND METHODS: There were 99 children with CM over 10-year period. Mini-laparotomy (ML), laparoscopy (LS) and laparotomy (LT) were used. We performed radical CM resection and bile duct reconstruction using Roux-en-Y hepaticojejunostomy (RYHJ) and hepaticoduodenostomy (HD). Surgery time, short-term and long-term postoperative outcomes were evaluated. RESULTS: ML was performed in 39 patients, LS - 51 patients, LT - 9 patients. In case of LS, hospital-stay was significantly lower after intracorporeal RYHJ formation compared to extracorporeal technique (p=0.02, Mann-Whitney U-test). Intracorporeal RYHJ requires more time (p=0.0003). Intestinal passage recovered 3 times faster in the ML RYHJ group compared to the LS RYHJ group (p=0.016, Mann-Whitney U-test). ML RYHJ was followed by significantly less duration of postoperative narcotic anesthesia compared to LS HD (3 vs. 4 days, p=0.02, Mann-Whitney U-test). In our study, ML RYHJ has an advantage over LS RYHJ regarding long-term outcomes. HD resulted higher incidence of severe postoperative pancreatitis (p=0.033) that required surgical correction (LT, p=0.043). CONCLUSION: ML RYHJ has some advantages over other methods of bile duct reconstruction. Therefore, we can currently recommend this method as a preferable one.

[Efficiency of minilaparotomy in the treatment of choledochal malformation in children]. / Otsenka effektivnosti mini-laparotomii pri lechenii mal'formatsii obshchego zhelchnogo protoka u detei.

OBJECTIVE: To evaluate an effectiveness of minilaparotomy in the treatment of choledochal malformation (CM) in children. MATERIAL AND METHODS: The study included children with CM who underwent surgery from January 2010 to May 2020. All patients were divided into 3 groups depending on surgical approach: minilaparotomy (ML), laparoscopy (LS) and laparotomy (LT). We analyzed surgery time, early postoperative outcomes and cosmetic results. RESULTS: There were 99 patients with CM for 10 years. ML was performed in 39 patients, LS - in 51 patients, and LT - in 9 patients. Significantly (p-value <0.001, Kruskal-Wallis test with Dunn paired comparison test, p<0.05) less surgery time was observed in ML group. According to Clavien-Dindo classification of surgical complications, we found a significant prevalence of complications in the LS group (p - 0.018, Kruskal-Wallis test). Moreover, LS was characterized by insignificant (p>0.05) predominance of the most severe complications requiring multiple redo surgeries. CONCLUSION: Currently, open surgery is a "gold standard" in the treatment of children with CM. LS is not preferred in children with CM. ML ensures favorable early outcomes in children with CM.

When It Doesn't Fit: Congenital Anomalies of the Choledochus.

Introduction Congenital choledochal malformations (CCMs) are characterized by intra- and/or extrahepatic bile duct dilatation. Five basic types (1-5) are recognized in Todani's classification and its modifications, of which types 1 and 4 typically have an associated anomalous pancreatobiliary junction and common channel (CC). We describe two cases with previously undescribed features. Case Report 1 Antenatal detection of a cyst at porta hepatis was made in an otherwise normal girl of Iranian parentage. She was confirmed to be a CCM (20 mm diameter), postnatally, with no evidence of obstruction. Surgical exploration was performed at 12 weeks. She had an isolated cystic dilatation of the right-hepatic duct only. The left-hepatic duct and common bile duct (CBD) were normal without a CC. Histology of the resected specimen showed stratified squamous epithelium. Case Report 2 A preterm (31 weeks of gestation) boy of Nigerian parentage was presented. His mother was HIV + ve and he was treated with nucleoside reverse transcriptase inhibitors following birth. He had persistent cholestatic jaundice and a dilated (10 mm) bile duct from birth. Although the jaundice resolved, the dilatation persisted and increased, coming to surgery aged 2.5 years. This showed cystic dilatation confined to the common hepatic duct, and otherwise normal distal common bile duct and no CC. Result Both underwent resection with the Roux-en-Y hepaticojejunostomy reconstruction to the transected right-hepatic duct alone in case 1, leaving the preserved left duct and CBD in continuity, and to the transected common hepatic duct in case 2. Conclusions Neither choledochal anomaly fitted into the usual choledochal classification and case 1 appears unique in the literature.

Long-term morbidity and follow-up after choledochal malformation surgery; A plea for a quality of life study.

Much about the aetiology, pathophysiology, natural course and optimal treatment of choledochal malformation remains under debate. Surgeons continuously strive to optimize their roles in the management of choledochal malformation. Nowadays the standard treatment is complete cyst excision followed by Roux-en-Y hepaticojejunostomy, be it via a laparotomy, laparoscopy or robot-assisted procedure. Whatever surgical endeavor is undertaken, it will be a major operation, with significant morbidity. It is important to realize that especially in asymptomatic cases, this is considered prophylactic surgery, aimed at preventing symptoms but even more important the development of malignancy later in life. A clear overview of long-term outcomes is therefore necessary. This paper aims to review the long-term outcomes after surgery for choledochal malformation. We will focus on biliary complications such as cholangitis, the development of malignancy and quality of life. We will try and identify factors related to a worse outcome. Finally, we make a plea for a large scale study into quality and course of life after resection of a choledochal malformation, to help patients, parents and their treating physicians to come to a well-balanced decision regarding the treatment of a choledochal malformation.

Preface - Pediatric hepatobiliary surgery.

This issue of Seminars in Pediatric Surgery reviews leading topics in pediatric hepatobiliary surgery where controversy exists and provides a learning resource to the subject.

Insights into the pathophysiology and classification of type 4 choledochal malformation.

INTRODUCTION: Type 4 choledochal malformations (CMs) can be defined as extra- and intrahepatic biliary dilatation. They are of uncertain etiology but make up about 20% of most series. The aim of this study was to investigate the pathophysiology and their natural history following surgical intervention. METHODS: Ambispective review of a single-center series of type 4 CM between 1996 and 2017. Perioperative imaging, intraoperative pressure monitoring, bile amylase, and long-term follow-up data were analyzed based on extrahepatic morphology [(cystic (C), fusiform (F)]. Data were expressed as median (range). Statistical analysis was performed with nonparametric tests. P < 0.05 was considered significant. RESULTS: 37 children had type 4 CM in the study period [age at surgery 4 (0.2-16) years] and could be further subdivided into cystic (4C) (n = 22) or fusiform (4F) (n = 15). There was significantly greater dilatation of the extrahepatic component in the cystic group [30 (11-94) versus 15 (8-90) mm; P = 0.0002] though there was no difference in left duct diameter [cystic 7.5 (0-17) mm versus fusiform 7.5 (3-16) mm; P = 0.86]. There was a trend to higher choledochal pressure in the cystic group [19 (4-40) versus 9 (6-25) mmHg; P = 0.09] and those in the fusiform group had higher bile amylase [8650 (3-890,000) versus 592 (1-123,000) IU/L; P = 0.01] and were older [4.1 (0.92-16.43) versus 2.4 (0.15-15.48) years; P = 0.03]. Children with type 4 CM were then separated simply on the basis of bile amylase into LOW (characterized by high pressure, cystic morphology and young age at surgery) and HIGH bile amylase (low pressure, fusiform morphology and older at time of surgery). CONCLUSIONS: We propose further division of type 4 CM into 4C and 4F on clinical and pathophysiological grounds. LEVEL OF EVIDENCE: II (prospective cohort).

Choledochal malformations in adults in the Netherlands: Results from a nationwide retrospective cohort study.

BACKGROUND AND AIMS: Patients with a choledochal malformation, formerly described as cysts, are at increased risk of developing a cholangiocarcinoma and resection is recommended. Given the low incidence of choledochal malformation (CM) in Western countries, the incidence in these countries is unclear. Our aim was to assess the incidence of malignancy in CM patients and to assess postoperative outcome. METHODS: In a nationwide, retrospective study, all adult patients who underwent surgery for CM between 1990 and 2016 were included. Patients were identified through the Dutch Pathology Registry and local patient records and were analysed to determine the incidence of malignancy, as well as postoperative mortality and morbidity. RESULTS: A total of 123 patients with a CM were included in the study (Todani Type I, n = 71; Type II, n = 10; Type III, n = 3; Type IV, n = 27; unknown, n = 12). Median age was 40 years (range 18-70) and 81% were female. The majority of patients (99/123) underwent extrahepatic bile duct resection, with additional liver parenchyma resections in eight patients, only exploration in two, and a local cyst resection in eight patients. Postoperative 30-day mortality was 2% (2/123) and limited to patients who underwent liver resection. Severe morbidity occurred in 24%. In 14 of the 123 patients (11%), a malignancy was found in the resected specimen. One patient developed a periampullary malignancy 7 years later. CONCLUSIONS: In a large Western series of CM patients, 11% were found to have a malignancy. This justifies resection in these patients, despite the risk of morbidity (24%) and mortality (2%).

Robot-Assisted Laparoscopic Resection of a Todani Type II Choledochal Malformation.

Choledochal malformation (CM) comprise various congenital cystic dilatations of the extrahepatic and/or intrahepatic biliary tree. CM is classified into five different types. Our case describes a 58-year-old man presenting with acute abdominal pain. Further examination showed a Todani type II CM. Treatment for type II is complete cyst excision without the need for an extrahepatic bile duct resection. A robot-assisted laparoscopic resection of the CM was performed and the patient recovered without complications. Pathology results showed a Todani type II malformation in which complete squamous metaplasia has occurred. In this paper, we report, to the best of our knowledge, the first description of a robot-assisted laparoscopic resection of a type II CM.

Choledochal malformations: global research, scientific advances and key controversies.

Choledochal malformations (CMs) represent a spectrum of relatively rare and complex congenital anomalies, characterized by abnormal dilatation of the biliary tract in the absence of any acute obstruction. Today, almost 20% of CMs can be detected in-utero using maternal ultrasonography. Formal scientometric analysis was used to identify where modern CM research is taking place and perhaps where our attention should be directed in the future. Thus, this article offers a comprehensive review of recent scientific advances relating to CMs including the current understanding of etiology and classification, whilst also discussing key controversies such as risk of malignant transformation and the role of newer modalities of surgical treatment. Although laparoscopic excision of CMs and biliary reconstruction is nowadays feasible and safe, care should be taken before dispensing with standard open techniques, which have minimal complication rates and proven long-term benefit.

Factors affecting the operating time for complete cyst excision and Roux-en-Y hepaticojejunostomy in paediatric cases of congenital choledochal malformation: a retrospective case study in Southeast China.

OBJECTIVE: The aim of this study was to evaluate factors affecting the operating time for complete cyst excision and Roux-en-Y hepaticojejunostomy in paediatric cases of congenital choledochal malformation (CCM). DESIGN: A 3-year retrospective study was undertaken between January 2013 and December 2015 in four centres in China. SETTING: This involved a retrospective chart review of paediatric patients with CCM in four large hospitals in Southeast China. PARTICIPANTS: Sixty-five paediatric patients with CCM were included in this study. We derived all available information on patient demographics, clinical characteristics, preoperative complications and surgical methods from the charts of all these patients. INTERVENTIONS: Univariate and multivariate logistic regression analyses were used to evaluate factors significantly affecting the operating time for complete cyst excision and Roux-en-Y hepaticojejunostomy in paediatric cases of CCM. RESULTS: Twenty-three of the 65 case surgeries were performed using laparoscopic technique, and 42 surgeries were performed by conventional open surgery. The median operating time was 215 min (range 120-430 min). The morphological subtype of CCM and the presence of cholecystitis or cholangitis were the only factors found to affect the operating time (p<0.05). Logistic regression analysis confirmed cholangitis as an independent risk factor. CONCLUSIONS: The morphological subtype of CMM and the presence of cholecystitis or cholangitis are factors affecting the operating time for complete cyst excision and Roux-en-Y hepaticojejunostomy in paediatric cases of CCM, whereas cholangitis is an independent risk factor.

The timing of surgery of antenatally diagnosed choledochal malformations: A descriptive analysis of a 26-year nationwide cohort.

INTRODUCTION: Choledochal malformations (CMs) are increasingly diagnosed antenatally. There is a dilemma between early surgery to prevent CM-related symptoms and postponing surgery to reduce complications. We aimed to identify the optimal timing of surgery in asymptomatic neonates with antenatally diagnosed CM and to identify predictors for development of symptoms. METHODS: Using the Netherlands Study group on CHoledochal Cyst/malformation (NeSCHoc) we retrospectively collected demographic, biochemical and surgical data from all Dutch patients with an antenatally detected CM. RESULTS: Between 1989 and 2014, antenatally suspected CM was confirmed in 17 patients at a median age of 10days (1day-2months). Four patients developed symptoms directly after birth (24%). Thirteen patients (76%) remained asymptomatic. Two of these progressed to symptoms before surgical intervention at 0.7 and 2.1months resp. Postoperatively, four patients developed short-term complications and three developed long-term complications. Patients <5.6kg (the series median) showed more short-term complications (66%) when compared to patients >5.6kg (0%, p=0.02). CONCLUSION: When not symptomatic within the first days of life, the majority of children with antenatally detected CM remains asymptomatic. Surgery might safely be delayed to the age of 6months or a weight of 6kg. Postponing surgery in the clinically and biochemical asymptomatic patient might decrease the complication rate. LEVELS OF EVIDENCE: Level III.

Biliary atresia and other cholestatic childhood diseases: Advances and future challenges.

Biliary Atresia and other cholestatic childhood diseases are rare conditions affecting the function and/or anatomy along the canalicular-bile duct continuum, characterised by onset of persistent cholestatic jaundice during the neonatal period. Biliary atresia (BA) is the most common among these, but still has an incidence of only 1 in 10-19,000 in Europe and North America. Other diseases such as the genetic conditions, Alagille syndrome (ALGS) and Progressive Familial Intrahepatic Cholestasis (PFIC), are less common. Choledochal malformations are amenable to surgical correction and require a high index of suspicion. The low incidence of such diseases hinder patient-based studies that include large cohorts, while the limited numbers of animal models of disease that recapitulate the spectrum of disease phenotypes hinders both basic research and the development of new treatments. Despite their individual rarity, collectively BA and other cholestatic childhood diseases are the commonest indications for liver transplantation during childhood. Here, we review the recent advances in basic research and clinical progress in these diseases, as well as the research needs. For the various diseases, we formulate current key questions and controversies and identify top priorities to guide future research.

Congenital choledochal malformation: search for a marker of epithelial instability.

PURPOSE: There is a predisposition to the development of malignancy in congenital choledochal malformation (CCM) although the degree of risk is unknown. We investigated the role of CA19-9 in bile and the MIB-1 (Ki-67) epithelial proliferation index as markers of an at risk choledochal epithelium at the time of definitive surgery. METHODS: Bile collected at surgery was analyzed for levels of amylase (as a surrogate of pancreatic reflux) and CA19-9. Immunohistochemical staining for CA19-9 and MIB-1 index (expressed as %) was performed on resected specimens. Data are quoted as median (IQR) and differences assessed using non-parametric statistics. A P value of 0.05 was regarded as significant. RESULTS: Our study group consisted of 78 children with CCM (Type 1 fusiform, n=34; Type 1 cystic, n=30 and Type 4, n=14). Median bile CA19-9 was 159,400 (6-1×10(6)) kU/L. There was no correlation with bile amylase (P=0.49) or biliary pressure (P=0.17) but modest correlation with bilirubin (rs=0.24; P=0.02). In contrast, bile amylase was correlated with plasma γ-glutamyl transpeptidase (P=0.02), alkaline phosphatase (P=0.05) and aspartate aminotransferase (P=0.02); and inversely correlated with biliary pressure (rs=-0.38; P<0.0008). Epithelial expression of CA19-9 and MIB-1 was assessed in 43 specimens. CA19-9 was diffusely expressed on all choledochal epithelium. MIB-1 expression was divided into: high expression (>40%) n=3; moderate (20-40%) n=5, low (6-20%) n=7 and very low (≤5%) n=28. There was no correlation with choledochal pressure (P=0.87), CA19-9 (P=0.51) or bile amylase (P=0.55). CONCLUSION: Biliary CA19-9 levels were grossly (and unexpectedly) raised in choledochal malformation and appear to arise from biliary rather than pancreatic epithelium. MIB-1 confirms that a small proportion (19%) has marked epithelial proliferation but no clinical correlates could be identified.

Growth in children with choledochal malformations: effect of the Roux loop.

PURPOSE: Excision and biliary reconstruction using a Roux loop is the current standard for choledochal malformation (CM). This is un-physiological, delivering bile beyond the duodenum and excluding a significant length of the jejunum from intestinal absorption. We investigated whether this had an effect on post-operative growth. METHODS: Retrospective case-note analysis of children surgically treated for CM. Growth variables were converted to standard deviation scores (SDS) and compared against population norms. P < 0.05 was significant. RESULTS: From 1994 to 2014, 135 children (<16 years) were identified. Median age at surgery was 3.3 (IQR 1.5-7) years. Morphology included: type 1 Cystic (n = 54, 40%), type 1 Fusiform (n = 58, 43%) and type 4 (intra and extra-hepatic) (n = 22, 16%). There was pre-operative growth failure [median weight SDS = -0.4 (-1.2 - 0.4), P = 0.0004] with a similar trend for height [SDS = -0.38 (-1.2 - 0.5), P = 0.08)]. This correlated with presentation bilirubin (r s = -0.24, P = 0.004), GGT (r s = -0.27, P = 0.002) and AST (r s = -0.27, P = 0.002) but not morphology (P = 0.82) or presentation (P = 0.4). Median follow-up was 1.9 (0.6-4.7) years, during which time both height (P = 0.73) and weight (P = 0.45) reverted to normal. CONCLUSION: This is the first report of growth in children with CM following a Roux-loop reconstruction and showed pre-operative growth failure probably attributed to a period of biliary obstruction but catch-up growth when corrected.