The Knudson’s Two-Hit Model and Timing of Somatic Mutation May Account for the Phenotypic Diversity of Focal Congenital Hyperinsulinism

Giurgea, Irina; Sempoux, Christine; Bellanné‐Chantelot, Christine; Ribeiro, Maria João; Hubert, Laurence; Boddaert, Nathalie; Saudubray, Jean‐Marie; Robert, Jean‐Jacques; Brunelle, Françis; Rahier, Jacques; Jaubert, Françis; Nihoul‐Feketé, Claire; Lonlay, Pascale de

doi:10.1210/jc.2006-0397

Cited by 34 publications

(29 citation statements)

References 42 publications

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“…After resection of the accumulation in the uncinate process, the diffuse involvement of the remaining pancreas became apparent. There are only a few cases described so far that really showed two or more independent focal lesions within an otherwise normal pancreas (27,28,30). Most cases of "newly " detected focal lesions after surgery are probably either remaining adenomatosis after an incomplete resection or unevenly distributed hyperactivities within the intermediate form of CHI.…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of [18F]Fluoro-l-DOPA Positron Emission Tomography-Computed Tomography for Surgery in Focal Congenital Hyperinsulinism

Barthlen

Blankenstein

Mau

et al. 2008

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context:In congenital hyperinsulinism (CHI), the identification and precise localization of a focal lesion is essential for successful surgery.Objective: Our objective was to evaluate the predictive value and accuracy of integratedfor the surgical therapy of CHI. Design:This was an observational study. Setting:The study was performed in the Department of Pediatric Surgery at a university hospital. Results: In nine children the intraoperative situation corresponded exactly to the description of the [18 F]FDOPA PET-CT. A limited resection of the pancreas was curative in eight cases at the first surgery, in one case at the second intervention. We observed no diabetes mellitus or exocrine insufficiency in the follow up so far. In one child, hypoglycemia persisted even after two partial resections of the pancreatic head. Histological analysis finally revealed an atypical intermediate form of CHI. Conclusions

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Section: Discussionmentioning

confidence: 99%

“…Therefore, we take multiple frozen sections from the remaining pancreatic tissue as recommended by other groups (11,32,33). Furthermore, the rare but existing possibility of a second or third focus within the pancreas must be considered to be a possible reason for failure of surgery (27,30).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of [18F]Fluoro-l-DOPA Positron Emission Tomography-Computed Tomography for Surgery in Focal Congenital Hyperinsulinism

Barthlen

Blankenstein

Mau

et al. 2008

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…Despite undergoing the second surgery this patient was reported to be dependent on continuous gastrostomy feeds to maintain euglycemia [12] . Giurgea et al [47] reported that the size of the focal lesion is determined by the timing when the somatic loss of maternal allele occurs during the gestational age [47] . The earlier it occurs the larger the size of the focal lesion can be, as found in the 3 patient in this report.…”

Section: F-dopa-pet/ct In Chimentioning

confidence: 99%

“…The earlier it occurs the larger the size of the focal lesion can be, as found in the 3 patient in this report. Also it has been suggested that an unknown mechanism might play a role in different rate of tracer uptake in different regions of pancreas in large focal lesions [47] . Meintjes et al [26] recently evaluated and reported the accuracy of delineating the focal and diffuse CHI using 18 F fluoro-L-DOPA/CT and contrast enhanced CT.…”

Section: F-dopa-pet/ct In Chimentioning

confidence: 99%

Congenital hyperinsulinism: Role of fluorine-18L-3, 4 hydroxyphenylalanine positron emission tomography scanning

Gopal‐Kothandapani

Hussain

2014

WJR

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Congenital hyperinsulinism (CHI) is a rare but complex heterogeneous disorder caused by unregulated secretion of insulin from the β-cells of the pancreas leading to severe hypoglycaemia and neuroglycopaenia. Swift diagnosis and institution of appropriate management is crucial to prevent or minimise adverse neurodevelopmental outcome in children with CHI. Histologically there are two major subtypes of CHI, diffuse and focal disease and the management approach will significantly differ depending on the type of the lesion. Patients with medically unresponsive diffuse disease require a near total pancreatectomy, which then leads on to the development of iatrogenic diabetes mellitus and pancreatic exocrine insufficiency. However patients with focal disease only require a limited pancreatectomy to remove only the focal lesion thus providing complete cure to the patient. Hence the preoperative differentiation of the histological subtypes of CHI becomes paramount in the management of CHI. Fluorine-18L-3, 4-hydroxyphenylalanine positron emission tomography ( 18 F-DOPA-PET) is now the gold standard for pre-operative differentiation of focal from diffuse disease and localisation of the focal lesion. The aim of this review article is to give a clinical overview of CHI, then review the role of dopamine in β-cell physiology and finally discuss the role of

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“…Because of the difficulty to ensure normoglycemia by the conservative treatment modalities, the standard treatment for patients with early-onset CHI has in many centers been near-total (95%) pancreatectomy [4, 18, 35, 36]. However, it has now become apparent that 30–60% of neonatal-onset CHI is caused by the focal form of the disease [8, 9, 37, 38]. In most cases, only a tiny pancreatic lobulus of <1 cm is affected.…”

Section: Differential Therapymentioning

confidence: 99%

[<sup>18</sup>F]-DOPA Positron Emission Tomography for Preoperative Localization in Congenital Hyperinsulinism

et al. 2008

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In recent years, considerable progress has been made in the biochemical, morphological and molecular genetic differentiation of congenital hyperinsulinism (CHI). Fluorine-18 L-3,4-dihydroxyphenylalanine positron emission tomography (¹⁸F-DOPA-PET) has been introduced for differentiation between focal and diffuse CHI. The ability to take up L-DOPA and convert it into dopamine is correlated with the activity of the aromatic amino acid decarboxylase and increased in the hyperfunctional affected pancreatic area in comparison to normally functioning pancreas. The high sensitivity of this method allows the surgeon to perform a curative limited resection of a focus without the risk of long-term diabetes. The exact preoperative planning by ¹⁸F-DOPA-PET/CT computer tomography allows laparoscopic operation in selected cases with the focus in the tail and limits necessity to open the pancreatic duct in cases with focus in the head. Patients with persistent CHI should be managed within a strong network of diagnostic, treatment, and research institutions.

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The Knudson’s Two-Hit Model and Timing of Somatic Mutation May Account for the Phenotypic Diversity of Focal Congenital Hyperinsulinism

Cited by 34 publications

References 42 publications

Evaluation of [18F]Fluoro-l-DOPA Positron Emission Tomography-Computed Tomography for Surgery in Focal Congenital Hyperinsulinism

Evaluation of [18F]Fluoro-l-DOPA Positron Emission Tomography-Computed Tomography for Surgery in Focal Congenital Hyperinsulinism

Congenital hyperinsulinism: Role of fluorine-18L-3, 4 hydroxyphenylalanine positron emission tomography scanning

[<sup>18</sup>F]-DOPA Positron Emission Tomography for Preoperative Localization in Congenital Hyperinsulinism

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