Objectives: To prospectively evaluate safety and efficacy of holmium laser enucleation of prostate (HoLEP) for surgical treatment of recurrent symptoms due to prostatomegaly after prior transurethral ...resection of prostate (TURP).
Materials and Methods: We prospectively evaluated 43 patients with a history of TURP who underwent HoLEP (study group). Patients in chronological order who underwent HoLEP without prior TURP were included in the control group. We hypothesized that prior TURP would increase technical difficulties, thereby leading to a reduction in procedure efficiency by 25%. Patients' demographic, intraoperative, and postoperative data were compared, and statistical analysis was performed.
Results: Demographic data in both groups were comparable. The average interval between past TURP and HoLEP was 4.22 years. There was no difficulty in identifying the dissection plane in the study group and the difference in the procedure efficiency between the study and the control groups were statistically insignificant (0.75 ± 0.31 g/min-study group vs. 0.69 ± 0.36 g/min-control group; P = 0.665). The intraoperative parameters and postoperative outcomes were comparable in both groups.
Conclusions: Prior TURP does not negatively impact the outcome of HoLEP in treating symptomatic recurrence for enlarged prostate after initial TURP.
Summary Wiedemann–Steiner Syndrome (WSS) is a rare condition characterised by short stature, hypertrichosis of the elbow, intellectual disability and characteristic facial dysmorphism due to ...heterozygous loss of function mutations in KMT2A, a gene encoding a histone 3 lysine 4 methyltransferase. Children with WSS are often short and until recently, it had been assumed that short stature is an intrinsic part of the syndrome. GHD has recently been reported as part of the phenotypic spectrum of WSS. We describe the case of an 8-year-old boy with a novel heterozygous variant in KMT2A and features consistent with a diagnosis of WSS who also had growth hormone deficiency (GHD). GHD was diagnosed on dynamic function testing for growth hormone (GH) secretion, low insulin-like growth factor I (IGF-I) levels and pituitary-specific MRI demonstrating anterior pituitary hypoplasia and an ectopic posterior pituitary. Treatment with GH improved height performance with growth trajectory being normalised to the parental height range. Our case highlights the need for GH testing in children with WSS and short stature as treatment with GH improves growth trajectory. Learning points: Growth hormone deficiency might be part of the phenotypic spectrum of Wiedemann–Steiner Syndrome (WSS). Investigation of pituitary function should be undertaken in children with WSS and short stature. A pituitary MR scan should be considered if there is biochemical evidence of growth hormone deficiency (GHD). Recombinant human growth hormone treatment should be considered for treatment of GHD.
Congenital Hyperinsulinism (CHI) is a disease of severe hypoglycaemia caused by excess insulin secretion and associated with adverse neurodevelopment in a third of children. The Vineland Adaptive ...Behavior Scales Second Edition (VABS-II) is a parent report measure of adaptive functioning that could be used as a developmental screening tool in patients with CHI. We have investigated the performance of VABS-II as a screening tool to identify developmental delay in a relatively large cohort of children with CHI. VABS-II questionnaires testing communication, daily living skills, social skills, motor skills and behaviour domains were completed by parents of 64 children with CHI, presenting both in the early neonatal period (Early-CHI, n = 48) and later in infancy (Late-CHI, n = 16). Individual and adaptive composite (Total) domain scores were converted to standard deviation scores (SDS). VABS-II scores were tested for correlation with objective developmental assessment reported separately by developmental paediatricians, clinical and educational psychologists. VABS-II scores were also investigated for correlation with the timing of hypoglycaemia, gender and phenotype of CHI.
Median (range) total VABS-II SDS was low in CHI -0.48 (-3.60, 4.00) with scores < -2.0 SDS in 9 (12%) children. VABS-II Total scores correctly identified developmental delay diagnosed by objective assessment in the majority odds ratio (OR) (95% confidence intervals, CI) 0.52 (0.38, 0.73), p < 0.001 with 95% specificity area under curve (CI) 0.80 (0.68, 0.90), p < 0.001 for cut-off < -2.0 SDS, although with low sensitivity (26%). VABS-II Total scores were inversely correlated (adjusted R
= 0.19, p = 0.001) with age at presentation (p = 0.024) and male gender (p = 0.036), males having lower scores than females in those with Late-CHI -1.40 (-3.60, 0.87) v 0.20 (-1.07, 1.27), p = 0.014. The presence of a genetic mutation representing severe CHI also predicted lower scores (R
= 0.19, p = 0.039).
The parent report VABS-II is a reliable and specific tool to identify developmental delay in CHI patients. Male gender, later age at presentation and severity of disease are independent risk factors for lower VABS-II scores.
Insulinomas are a rare cause of hyperinsulinaemic hypoglycaemia (HH) in children. The clinical features, investigations, management and histology of these rare pancreatic tumours in children have not ...been described in a large cohort of patients.
We conducted a retrospective review of cases diagnosed between 2000 and 2012, presenting to two referral centres in the United Kingdom. Clinical, biochemical, imaging (magnetic resonance imaging (MRI) and 6-L-¹⁸F-fluorodihydroxyphenylalanine (¹⁸F-DOPA) PET/CT scanning) and histological data were collected.
Nine children (age range 2-14.5 years) were diagnosed during the study period at Great Ormond Street Hospital (n=5) and Royal Manchester Children's Hospital (n=4). The combination of abdominal MRI scan (7/8) and ¹⁸F-DOPA PET/CT scan (2/4) correctly localised the anatomical location of all insulinomas. Before surgery, diazoxide therapy was used to treat hypoglycaemia, but only four patients responded. After surgical resection of the insulinoma, hypoglycaemia resolved in all patients. The anatomical localisation of the insulinoma in each patient was head (n=4), uncinate process (n=4) and tail (n=2, one second lesion) of the pancreas. Histology confirmed the diagnosis of insulinoma with the presence of sheets and trabeculae of epithelioid and spindle cells staining strongly for insulin and proinsulin, but not for glucagon or somatostatin. Two children were positive for MEN1, one of whom had two separate insulinoma lesions within the pancreas.
We describe a cohort of paediatric insulinoma patients. Although rare, insulinomas should be included in the differential diagnosis of HH, even in very young children. In the absence of a single imaging modality in the preoperative period, localisation of the tumour is achieved by combining imaging techniques, both conventional and functional.
Primitive neuroectodermal tumor (PNET) of the kidney is an extremely rare renal neoplasm with only about 50 reported cases in the literature. These tumors behave aggressively and carry a poor ...prognosis. A 22 years female patient presented with right lumber and right hypochondrium lump of 4 months duration. Commutated tomography revealed large right renal mass with renal vein and inferior vena cava (IVC) thrombus. Magnetic resonance imaging abdomen demonstrated the extension of tumor thrombus up to the junction of hepatic vein and IVC. Preoperative percutaneous needle biopsy was performed. Histopathology demonstrated small round to oval cells with scanty cytoplasm and cells are arranged in clusters. Immunohistochemical staining demonstrated a highly specific cluster of differentiation 99, confirming the diagnosis of a PNET.
Sphingosine-1-phosphate lyase (SGPL1) insufficiency syndrome (SPLIS) is an autosomal recessive multi-system disorder, which mainly incorporates steroid-resistant nephrotic syndrome and primary ...adrenal insufficiency. Other variable endocrine manifestations are described. In this study, we aimed to comprehensively annotate the endocrinopathies associated with pathogenic SGPL1 variants and assess for genotype–phenotype correlations by retrospectively reviewing the reports of endocrine disease within our patient cohort and all published cases in the wider literature up to February 2022. Glucocorticoid insufficiency in early childhood is the most common endocrine manifestation affecting 64% of the 50 patients reported with SPLIS, and a third of these individuals have additional mineralocorticoid deficiency. While most individuals also have nephrotic syndrome, SGPL1 variants also account for isolated adrenal insufficiency at presentation. Primary gonadal insufficiency, manifesting with microphallus and cryptorchidism, is reported in less than one-third of affected boys, all with concomitant adrenal disease. Mild primary hypothyroidism affects approximately a third of patients. There is paucity of data on the impact of SGPL1 deficiency on growth, and pubertal development, limited by the early and high mortality rate (approximately 50%). There is no clear genotype–phenotype correlation overall in the syndrome, with variable disease penetrance within individual kindreds. However, with regards to endocrine phenotype, the most prevalent disease variant p.R222Q (affecting 22%) is most consistently associated with isolated glucocorticoid deficiency. To conclude, SPLIS is associated with significant multiple endocrine disorders. While endocrinopathy in the syndrome generally presents in infancy, late-onset disease also occurs. Screening for these is therefore warranted both at diagnosis and through follow-up.
Congenital hyperinsulinism (CHI) causes dysregulated insulin secretion which can lead to life‐threatening hypoglycaemia if not effectively managed. CHI can be sub‐classified into three distinct ...groups: diffuse, focal and mosaic pancreatic disease. Whilst the underlying causes of diffuse and focal disease have been widely characterised, the genetic basis of mosaic pancreatic disease is not known. To gain new insights into the underlying disease processes of mosaic‐CHI we studied the islet tissue histopathology derived from limited surgical resection from the tail of the pancreas in a patient with CHI. The underlying genetic aetiology was investigated using a combination of high depth next‐generation sequencing, microsatellite analysis and p57kip2 immunostaining. Histopathology of the pancreatic tissue confirmed the presence of a defined area associated with marked islet hypertrophy and a cytoarchitecture distinct from focal CHI but compatible with mosaic CHI localised to a discrete region within the pancreas. Analysis of DNA extracted from the lesion identified a de novo mosaic ABCC8 mutation and mosaic paternal uniparental disomy which were not present in leukocyte DNA or the surrounding unaffected pancreatic tissue. This study provides the first description of two independent disease‐causing somatic genetic events occurring within the pancreas of an individual with localised mosaic CHI. Our findings increase knowledge of the genetic causes of islet disease and provide further insights into the underlying developmental changes associated with β‐cell expansion in CHI.
Congenital Hyperinsulinism (CHI) is an important cause of severe and persistent hypoglycaemia in infancy and childhood. The focal form (CHI-F) of CHI can be potentially cured by pancreatic ...lesionectomy. While diagnostic characteristics of CHI-F pancreatic histopathology are well-recognized, correlation with clinical phenotype has not been established.
We aimed to correlate the diversity in clinical profiles of patients with islet cell organization in CHI-F pancreatic tissue.
Clinical datasets were obtained from 25 patients with CHI-F due to
mutations.
F-DOPA PET-CT was used to localize focal lesions prior to surgery. Immunohistochemistry was used to support protein expression studies.
In 28% (
= 7) of patient tissues focal lesions were amorphous and projected into adjoining normal pancreatic tissue without clear delineation from normal tissue. In these cases, severe hypoglycaemia was detected within, on average, 2.8 ± 0.8 (range 1-7) days following birth. By contrast, in 72% (
= 18) of tissues focal lesions were encapsulated within a defined matrix capsule. In this group, the onset of severe hypoglycaemia was generally delayed; on average 46.6 ± 14.3 (range 1-180) days following birth. For patients with encapsulated lesions and later-onset hypoglycaemia, we found that surgical procedures were curative and less complex.
CHI-F is associated with heterogeneity in the organization of focal lesions, which correlates well with clinical presentation and surgical outcomes.
Congenital hyperinsulinism causes profound hypoglycemia, which may persist or resolve spontaneously. Among 13 children with congenital hyperinsulinism, elevated incretin hormone concentrations were ...detected in 2 with atypical, persistent disease. We suggest that incretin biomarkers may identify these patients, and that elevated hormone levels may contribute to their pathophysiology.
Congenital hyperinsulinism (CHI) is a rare condition but is a common cause of severe and persistent hypoglycemia in early life. Prompt recognition of CHI is critical to prevent the impact of ...neuroglycopenia and consequent lifelong neurodisability. It is important to be alert to the possibility of CHI in newborn babies with recurrent hypoglycemia associated with high glucose requirements. Pediatricians are advised to mitigate the risk of hypoglycemia by early treatment with high concentration dextrose and intravenous glucagon infusions. Specific medical therapies with diazoxide and/or somatostatin receptor analogues may be commenced after the finding of detectable insulin at hypoglycemia, a biochemical characteristic of CHI. Early exploration of genetic etiology is recommended, chiefly in the search for a focal form, amenable to limited pancreatic surgery. Genetic ascertainment is also useful to understand the basis of disease, variable responses to medical therapies and escalation of conservative treatment to subtotal pancreatectomy. CHI is a heterogeneous disorder with varying natural history. Many newborns and infants with CHI have severe and complex illness features; their long-term care is best achieved through review at specialist centers.
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