Clinical Relevance of Pathological Diagnosis of Hirschsprung's Disease with Acetylcholine-Esterase Histochemistry or Calretinin Immunohistochemistry.

INTRODUCTION: Hirschsprung disease (HD) manifests as a developmental anomaly affecting the enteric nervous system, where there is an absence of ganglion cells in the lower part of the intestine. This deficiency leads to functional blockages within the intestines. HD is usually confirmed or ruled out through rectal biopsy. The identification of any ganglion cells through hematoxylin and eosin (H&E) staining rules out HD. If ganglion cells are absent, further staining with acetylcholine-esterase (AChE) histochemistry or calretinin immunohistochemistry (IHC) forms part of the standard procedure for determining a diagnosis of HD. In 2017, our Institute of Pathology at University Hospital of Heidelberg changed our HD diagnostic procedure from AChE histochemistry to calretinin IHC. In this paper, we report the impact of the diagnostic procedure change on surgical HD therapy procedures and on the clinical outcome of HD patients. METHODS: We conducted a retrospective review of the diagnostic procedures, clinical data, and postoperative progress of 29 patients who underwent surgical treatment for HD in the Department of Pediatric Surgery, University of Heidelberg, between 2012 and 2021. The patient sample was divided into two groups, each covering a treatment period of 5 years. In 2012-2016, HD diagnosis was performed exclusively using AChE histochemistry (AChE group, n = 17). In 2017-2021, HD diagnosis was performed exclusively using calretinin IHC (CR group, n = 12). RESULTS: There were no significant differences between the groups in sex distribution, weeks of gestation, birth weight, length of the aganglionic segment, or associated congenital anomalies. Almost half of the children in the AChE group, twice as many as in the CR group, required an enterostomy before transanal endorectal pull-through procedure (TERPT). In the AChE group, 4 patients (23.5%) required repeat bowel sampling to confirm the diagnosis. Compared to the AChE group, more children in the CR group suffered from constipation post TERPT. DISCUSSION: Elevated AChE expression is linked to hypertrophied extrinsic cholinergic nerve fibers in the aganglionic segment in the majority of patients with HD. The manifestation of increased AChE expression develops over time. Therefore, in neonatal patients with HD, especially those in the first 3 weeks of life, an increase in AChE reaction is not detected. Calretinin IHC reliably identifies the presence or absence of ganglion cells and offers multiple benefits over AChE histochemistry. These include the ability to perform the test on paraffin-embedded tissue sections, a straightforward staining pattern, a clear binary interpretation (negative or positive), cost-effectiveness, and utility regardless of patient age. CONCLUSIONS: The ability of calretinin IHC to diagnose HD early and time-independently prevented repeated intestinal biopsies in our patient population and allowed us to perform a one-stage TERPT in the first months of life, reducing the number of enterostomies and restoring colonic continuity early. Patients undergoing transanal pull-through under the age of 3 months require a close follow-up to detect cases with bowel movement problems.

Image-guided percutaneous sclerotherapy of venous malformations of the head and neck: Clinical and MR-based volumetric mid-term outcome.

OBJECTIVE: To report the clinical and MRI-based volumetric mid-term outcome after image guided percutaneous sclerotherapy (PS) of venous malformations (VM) of the head and neck. METHODS: A retrospective analysis of a prospectively maintained database was performed, including patients with VM of the head and neck who were treated with PS. Only patients with available pre- and post-interventional MRI were included into this study. Clinical outcome, which was subjectively assessed by the patients, their parents (for paediatric patients) and/or the physicians, was categorized as worse, unchanged, minor or major improvement. Radiological outcome, determined by MRI-based volumetric measurements, was categorized as worse (>10% increase), unchanged (≤10% increase to <10% decrease), minor (≥10% to <25% decrease), intermediate (≥25% to <50% decrease) or major improvement (≥50% decrease). RESULTS: Twenty-seven patients were treated in 51 treatment sessions. After a mean follow-up of 31 months, clinical outcome was worse for 7.4%, unchanged for 3.7% of the patients, while there was minor and major improvement for 7.4% and 81.5%, respectively. In the volumetric imaging analysis 7.4% of the VMs were worse and 14.8% were unchanged. Minor improvement was observed in 22.2%, intermediate improvement in 44.4% and major improvement in 11.1%. The rate of permanent complications was 3.7%. CONCLUSION: PS can be an effective therapy to treat the symptoms of patients with VMs of the head and neck and to downsize the VMs. MRI-based volumetry can be used to objectively follow the change in size of the VMs after PS. Relief of symptoms frequently does not require substantial volume reduction.

Reference values for left and right ventricular trabeculation and non-compacted myocardium.

BACKGROUND: Since the differentiation between physiological and pathological trabeculation is challenging, we assessed its distribution in a reference population of selected healthy volunteers. METHODS: We studied 117 subjects (58 males) stratified into age tertiles and by gender. Cardiovascular magnetic resonance images were acquired using a standard SSFP-sequence. Left and right ventricular (LV/RV) end-diastolic (EDV), end-systolic (ESV) and trabeculated volumes indexed to the body surface area as well as ejection fraction (EF) were quantified in short-axis views. The maximum non-compacted-to-compacted (NC/C) ratio was measured in long-axis views. RESULTS: The trabeculated volumes were significantly larger in men than in women and decreased with age. The correlation between both was moderate (r=0.46; p<0.001). LV trabeculated volume was positively associated with EDV and ESV (r=0.74; r=0.59; both p<0.001) and negatively with EF (r=-0.27; p<0.005). It was no independent predictor for EF. The maximum NC/C ratio was >2.3 in 46.2% and >2.5 in 37.6% of the subjects, which is regarded as abnormal in current literature. The fraction of subjects with a maximum NC/C ratio >2.3 and the mean maximum NC/C ratio differed significantly between gender but not between age groups. An increasing NC/C ratio was associated with a significant decrease in EF (r=-0.21; p<0.05). CONCLUSION: A considerable amount of healthy volunteers fulfils the current diagnostic criteria of LV noncompaction with female subjects showing a higher fraction of false-positive results than males. LV trabeculated volume is more pronounced in young subjects and declines with age. The use of age- and gender-specific reference values as provided in this study may facilitate the delineation of physiological and pathological findings.