Elsevier

Journal of Pediatric Urology

Volume 12, Issue 2, April 2016, Pages 89.e1-89.e5
Journal of Pediatric Urology

Changes in Cajal cell density in ureteropelvic junction obstruction in children

https://doi.org/10.1016/j.jpurol.2015.08.010Get rights and content

Summary

Introduction

Congenital ureteropelvic junction obstruction is one the most common causes of neonatal hydronephrosis. The etiology of the ureteropelvic junction (UPJ) obstruction has not been clearly established. The presence of a hypoplastic, adynamic ureteral segment is thought to be the major cause of an UPJ obstruction.

Objective

We evaluated the distribution of Cajal cells using immunohistologic methods coupled with light microscopy of the UPJ tissues in obstructed and normal UPJs.

Study design

The study group consisted of 19 patients who underwent pyeloplasty for UPJ obstruction. Twelve patients who had been operated on for oncological indications constituted the control group. The sections were stained immunohistochemically using CD117 (c-kit) antibody; the numbers of CD117 (+) interstitial cells of Cajal were counted in 10 consecutive high-power fields under the light microscope and the cell density was determined for each case.

Results

The mean age of the cases who underwent dismembered pyeloplasty and the control group were 116 ± 116 months (14 male, 5 female; 6–420 months) and 279 ± 312 months (9 male, 3 female; 24–948 months) (p = 0.1), respectively. The mean interstitial Cajal cell number in the UPJ obstruction and the control groups were 2.37 ± 2.19 and 24.5 ± 9.73, respectively (p < 0.0001). Thirteen (68.4%) patients had very few, five (26.3%) patients had few, and one (5.3%) patient had many Cajal cells in the UPJ obstruction group. In the control group, all patients had more than seven cells per high-power field.

Discussion

We found that in cases of UPJ, obstruction the numbers of interstitial Cajal cells were decreased, being either absent or significantly reduced. Although data about the motility are currently not sufficient, the decrease in the number of Cajal cells in patients with UPJ highlights that they might be responsible for the initiation, coordination, and conduction of peristaltic activity along the pelvicalyceal system. Improvement and enhancement of contraction waves arising from the upper urinary system depend on interstitial cells of Cajal, which are the pacemaker cells in smooth muscles. We think that a decreased number of interstitial cells of Cajal have a close relationship with changing ureteral motility when we compare our UPJ obstruction cases with the limited data in the literature.

Conclusion

Further investigations on these cells will probably give detailed information about the neurophysiology of the urinary system and the diseases that cause congenital hydronephrosis.

  1. Download : Download high-res image (132KB)
  2. Download : Download full-size image

Figure. CD117 (+) Cajal cells (arrows) in the material from patients who had ureteropelvic junction obstruction.

Introduction

Congenital ureteropelvic junction (UPJ) obstruction is one the most common causes of neonatal hydronephrosis and its incidence is about one in 1500–2000 [1], [2]. UPJ obstruction is more common in boys rather than in girls and is more often seen in the left ureter. Most infants are asymptomatic and diagnosis is given generally by antenatal ultrasonography. Flank or abdominal pain, nausea, vomiting, hematuria, palpable abdominal mass, renal stones, or severe hypertension may be seen in some of the patients [2], [3]. The presence of hypoplastic adynamic segment is among the pathologies seen (e.g. crossing vessel, dysplastic segment, high insertion, etc.) [4].

Interstitial cells of Cajal (ICC) have been identified as one of the probable pacemaker cells for contractile activity of the ureter. They were first described by Santiago Ramon y Cajal in 1893 [5], [6]. Histologically, ICC are usually the same size or a little smaller than the smooth muscle cells beside them. However, their shape may differ: the ones located in between smooth muscle cells are more fusiform, and the ones located around the neuronal plexuses are usually stellate shaped [7], [8]. Their cytoplasm is rich in caveola, mitochondria, and thick intermediate filaments [9]. On their cytoplasmic membranes, they form tight gap junctions creating a network allowing cross-talking between them, which is enriched by the branching of fusiform or stellate-shaped cells forming ICC groups [9]. ICC express a tyrosine kinase receptor “c-kit (CD117)”, a feature allowing them to be recognized easily by immunohistochemistry under a light microscope [10].

It has been shown that ICC in the upper urinary tract may be responsible for the conduction of slow-wave electrical potentials between neurons and typical smooth muscle cells [11]. These slow waves activate the ion channels in smooth muscles and start the contraction cascade through which urine is carried from the renal pelvis to the ureter by peristaltism [12]. Therefore, it was thought that the absence of CD117 (+) ICC may result in the loss of peristaltic waves in the UPJ and, consequently, the transmission of urine to the ureter is impaired and a relative UPJ obstruction develops. An experimental study conducted by Ward et al. [13] revealed that slow waves have been lost in rats without ICC and, as a result, the coordination of peristaltism through the intestines has been disturbed. Therefore, these cells may play an important role in the initiation, propagation, coordination, and modulation of upper urinary tract peristalsis as well.

This study has been conducted to investigate the presence and determine the distribution of ICC in tissues resected from patients with UPJ obstruction and compare the results with the control group.

Section snippets

Materials and methods

Indications for pyeloplasty in our study group were acute symptoms of obstruction, unresponsiveness to a standard dose of furosemide in the dynamic renogram and/or increase in the anteroposterior diameter of the ipsilateral renal pelvis. Excisional biopsies with a resection margin of 2–3 mm above and below the UPJ in 19 patients who had undergone pyeloplasty due to UPJ obstruction were retrieved from the archives of the Department of Pathology. Three to six sections per case were re-evaluated

Results

The mean age of the 19 cases who underwent dismembered pyeloplasty and the control group were 116 ± 116 months (14 male, 5 female; 6–420 months) and 279 ± 312 months (9 male, 3 female; 24–948 months) (p = 0.1), respectively. Clinicopathologic parameters of all cases are summarized in Table 1. There was no significant correlation between duration, severity of obstruction, and acute episodes of renal colic and the number of ICC cells in the study group (p > 0.05). The mean Cajal cell numbers in

Discussion

It is proposed that, ICC are responsible for the peristaltic movements in the upper urinary system. They are supposed to be responsible for the coordinated ureteropelvic peristaltic movements in the intercalyceal area, and as a result of these movements conduction of the urine from the calyceal system through the ureter to the bladder [15]. Animal studies support the role of ICC in intestinal motility [16]. Reduction of ICC is found associated with disorders such as Hirschsprung disease [17],

Conflict of interest

None.

Funding

None.

References (30)

  • D.I. Williams et al.

    The prognosis of pelviureteric obstruction in childhood: a review of 190 cases

    Eur Urol

    (1976)
  • Louis R. Kavoussi et al.

    Campbell-Walsh Urology

    (2014)
  • S.R. Cajal
    (1911)
  • S.R. Cajal

    Sur les ganglions et plexus nerveux d’intestin (Abstract)

    CR Soc Bio

    (1893)
  • M. Costa et al.

    Anatomy and physiology of the enteric nervous system

    Gut

    (2000)
  • Cited by (21)

    • Role of ureterocalicostomy in management of giant hydronephrosis in children in contemporary practice: Indications, outcomes and challenges

      2021, Journal of Pediatric Urology
      Citation Excerpt :

      When the lower pole of the affected kidney is too dependent in the setting of GH or SFU Grade V, so that it reaches beyond lumber vertebra 4 and 5 corresponding to iliac crest, the drainage of the kidney through UPJ is inadequate, even if it is patent (Non-dependent UPJ, Fig. 1A) [11]. Further in GH, peristalsis in the collecting system is barely effective on account of loss of Interstitial cells of Cajal (ICC) and pacemakers in minor calyces [12,13]. In such situations urine drainage primarily occurs due to gravity alone, particularly when most of the dilation is intrarenal rather than extrarenal [11–14].

    • Comparison of different pathological markers in predicting pyeloplasty outcomes in children

      2020, Journal of Pediatric Surgery
      Citation Excerpt :

      While pyeloplasty is generally a successful surgery [1,25] on 5–7% occasions it fails [2,3]. While some authors have found little evidence to support a histological basis for pyeloplasty outcomes [16,26], others have identified presence of abnormalities in ICC, neurons and collagen-muscle matrix at UPJ [1–15,16,19–29]. Several of these histological markers like ICC, neurons and CM ratio have been reported to be of prognostic significance.

    • The search for the definition, etiology, and effective diagnosis of upper urinary tract obstruction: the Whitaker test then and now

      2019, Journal of Pediatric Urology
      Citation Excerpt :

      Solari et al. [28] first proposed that the altered density of c-Kit positive cells in UPJ obstruction may have a role in the failure of transmission of peristaltic waves across the UPJ. Senoll et al. [29] added to this body of inquiry, proving a decreased density of Cajal cells at the UPJ of patients operated on for UPJ obstruction. They investigated the UPJs of 19 pyeloplasty patients and 12 nephrectomy controls at a mean age of 116 months (14 males, 5 females) and 279 (9 males, 3 females), respectively.

    • Hydronephrosis and crossing vessels in children: Optimization of diagnostic-therapeutic pathway and analysis of color Doppler ultrasound and magnetic resonance urography diagnostic accuracy

      2018, Journal of Pediatric Urology
      Citation Excerpt :

      In most pediatric cases it is due to an intrinsic UPJ obstruction (UPJO) caused by abnormal smooth muscle development and fibrosis [1,2]. Some authors have proposed that the cause of the stenosis is a reduction in Cajal cell density, which leads to an alteration of ureteral motility [3,4]. In intrinsic cases, indications for surgery are impaired by split renal function (<40%), decrease of split renal function >10% in subsequent studies, increased anteroposterior diameter on ultrasound, and grade III and IV dilatation, as defined by the Society for Fetal Urology [5,6].

    • Diagnostic Imaging: Pediatrics

      2017, Diagnostic Imaging: Pediatrics
    View all citing articles on Scopus
    View full text