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

Introduction

Choledochal malformation (CM) is a rare disease with surgical resection mostly performed in infancy or during childhood [1, 2]. With 1:1,000 live births, its incidence in Asian countries [3], [4], [5] is considerably higher than in Europe, where actual numbers report on an incidence of 1:59,000 live births in the Netherlands [6]. The reason for this Asian predominance is not clear yet [3].

Patients with CM have an increased risk of hepatobiliary malignancies [7]. However, hepatobiliary tumors associated with CM usually occur during adulthood [8] and in rare cases in children or adolescents after CM resection [7]. Reports on malignancies following CM resection mostly were from Asian countries. In contrast, European follow-up studies from the United Kingdom and the Netherlands did not observe any malignancies following CM resection [6, 9]. Nevertheless, lifelong postoperative follow-up including sonography and CA19-9-determination has been recommended for all patients who underwent CM resection [7].

Although a major number of patients after CM resection in childhood have now reached adulthood, there are no studies reporting on the transition of patients after CM resection in to adult medical care. There is also no data on the quality of life of patients following CM resection. We hypothesized that the majority of patients who had undergone CM resection during childhood in Germany and now have reached adulthood are lost to follow-up and have never carried out transition into adult medical care.

Patients and methods

The study was approved by the local ethics committee (Number 8230_BO_K_2018). We included all pediatric and adolescent patients who had undergone surgery for CM in our department from January 1978 to June 2009. Medical records of these patients were reviewed and data on operation and early postoperative course were analyzed retrospectively.

Additionally, all patients were contacted by post and offered an appointment in our outpatient clinic for follow-up. Patients who agreed to participate received the PedsQL questionnaire and a standardized questionnaire concerning their postoperative clinical course and their gastroenterologic follow-up investigations. Patients who did not respond to our letters were additionally contacted by telephone and asked about their clinical course including complications and their past and present gastroenterologic follow-up investigations using the above-mentioned standardized questionnaires. Contacting of the patients, telephone interviews and clinical examinations were carried out by two of the authors (R.A. and N.S.). Patients gave informed consent on their participation.

Results

Health-related quality of life (HRQOL)

Median health-related quality of life scores were high for all patients: median total health score was 89; median physical health and median psychosocial health score were 94 and 87, respectively. There was no significant difference in the HRQOL scores of our patients in comparison to the healthy population (Figure 1). In detail, the mean physical functioning score was 94, the mean emotional functioning score was 80, the mean social functioning score was 96, and the mean school/work functioning score was 92.

Figure 1:

PedsQL mean summary scores. Mean summary scores in patients after CM resection compared with healthy population according to PedsQL [Varni et al. [11]]. Physical summary score consists of the PedsQL physical functioning score. Psychosocial summary score consists of emotional, social, and school functioning score. Total summary score consists of physical and psychosocial summary score. Data given in mean±standard deviation.

Discussion

Transition into adult medical care has become an important issue in the care of pediatric surgical conditions, especially hepatobiliary diseases [13, 14]. In the recent years, numerous studies dealt with the long-term outcome after CM resection, but these studies are focused rather on long-term complications than on patients’ transition into adult medical care [6, 15]. There is only few data from large cohorts of adult patients following CM resection in childhood.

In a recent publication from a single center in Japan [16], the authors evaluated the postoperative complications in 79 adult patients who had undergone pediatric CM resection. After a median postoperative period of 24.5 years, the authors found that 54.3 % attended postoperative follow-up. No patient had biliary carcinoma. Twelve patients (34.2 %) had postoperative complications. Out of these, six underwent regular checkups [16]. In another recent Japanese study, Mukai et al. [17] reported on the long-term outcomes of surgery for CM, focusing on follow-up and late complications. In their retrospective study including 110 patients, the authors found intrahepatic bile duct dilatation in 0.9 %, intrahepatic bile duct stones in 2.7 %, and adhesive ileus in 3.6 % of patients within 20 years after surgery. There was no biliary carcinoma in their series. Their overall follow-up rate was 37.3 %, and the follow-up rate declined to 14.5 % in patients who had undergone surgery more than 20 years previously to the study. The authors concluded that patients after CM resection should be followed-up by adult gastroenterologists [17].

In contrast, an increased risk of malignancy has been reported by numerous other Japanese authors [18], [19], [20]. In a large study from Japan including 1,353 pediatric and adult patients with choledochal malformation, the group reported an incidence of 16.2 % malignancy associated with primary CM and 0.7 % following CM resection [19]. Our group had conducted a review article and recommended a structured follow-up program following CM resection with yearly clinical, biomedical, and sonographic examinations of patients after CM resection [7]. In a recently published international survey among pediatric hepatobiliary surgeons and gastroenterologists, 91 % of respondents stated that a structured follow-up program after CM resection was available in their department [1].

The high drop-out rate from follow-up identified by Mukai et al. [17] is in accordance to our findings. We confirmed a drop-out rate of 78 % already at a median time of 4.3 years after CM resection. The majority of complications seen in our study were apparent in patients who fulfilled transition. Three patients had a complicated long-term postoperative course; in one patient, complications started after more than three decades of uneventful postoperative course.

Regarding the higher incidence of CM in Asian countries, data from Japan may not necessarily be transferable to European conditions. So far, there have only been two series dealing with long-term complications after CM resection in a European country. In a retrospective study [6], the short- and long-term complications in 91 pediatric patients who underwent CM resection in the Netherlands have been reported. No malignancy was identified during follow-up. The complication rate of 40 % (22 % short-term and 18 % long-term) was somehow similar to the rate of 35 % found in our study. Another European study has been recently published by Hyvärinen et al. who reported on the outcome after CM resection in 55 pediatric patients after a median follow-up of 5.8 years. In this collective, 21 % had long-term complications including one case of hepatocellular carcinoma [21]. According to the findings of Eijnden and in contrast to those of Hyvärinen [6, 21], we did not find any case of malignancy even in long-term follow-up in our collective. As recently published, we recommended life-long follow-up due to an elevated risk of malignancy [7]. Our present data confirm a loss follow-up in CM patients and emphasizes the importance of a life-long follow-up in CM patients in order to identify late postoperative sequelae in an early stage.

The only study on HRQOL in patients after pediatric CM resection until date was published by Baba et al. [16]. They compared the HRQOL of patients with postoperative vs. without postoperative complications. Among 79 patients, more than 18 years of age 35 (44.4 %) had answered the questionnaires after a median postoperative period of 24.5 years (range 5–31). HRQOL was significantly lower in patients with complications in all health domains. In our present study, we compared HRQOL of patients after CM resection to scores in a healthy population and found no significant difference between both groups. It may be speculated that this fact may substantially contribute to loss of follow-up. However, given the high rate of long-term sequelae we found in our cohort, the high drop-out rate might also be due to poor results and unwillingness to response.

Our present study has limitations. The first limitation is the low response rate, which limits the generalization of our findings. There might also be some bias in comparing the HRQOL of our German population with children from the United States. In addition, the small number of our patients makes statistical analysis difficult and impairs the explanatory power of our results. One weakness of both above mentioned studies of Mukai and Eijnden [6, 17] when compared to our present study was the sole retrospective aspect of using hospital databases to determine follow-up rate and complications. In contrast, we contacted patients and, therefore, were able to include also those ones who received follow-up investigations or medical treatment in other institutions. Furthermore, as most of our patients had a Todani type 1 cyst, and the two patients with a Todani type 4 cyst had no complications, we cannot make a statement whether the cyst type has an influence on the development of complications.

Conclusions

We confirmed that the majority of patients after resection of a CM are lost to follow-up. We found no case of malignancy but identified some severe long-term sequelae following an initially uneventful postoperative course. Given the high rate of severe long-term complications and the life-long risk of malignancy reported from other authors, we recommend a transition program and systematic follow-up for patients after CM resection into adulthood.