Gastrointestinal and Retroperitoneal Manifestations of Type 1 Neurofibromatosis

Basile, Ursula; Cavallaro, Giuseppe; Polistena, Andrea; Giustini, Sandra; Orlando, G.; Cotesta, Dario; Petramala, Luigi; Letizia, Claudio; Calvieri, Stefano; Toma, Giorgio De

doi:10.1007/s11605-009-0940-5

Cited by 65 publications

(49 citation statements)

References 57 publications

(48 reference statements)

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“…café-au-lait spots, axillary and inguinal freckling, iris hematomas and optic gliomas (Basile et al 2010, Relles et al 2010, Pasmant et al 2012. The prevalence of NF1 is about 1 in 3000 individuals.…”

Section: :9mentioning

confidence: 99%

Genetic and epigenetic drivers of neuroendocrine tumours (NET)

Domenico

Wiedmer

Perren

2017

Endocrine-Related Cancer

106

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Neuroendocrine tumours (NET) of the gastrointestinal tract and the lung are a rare and heterogeneous group of tumours. The molecular characterization and the clinical classification of these tumours have been evolving slowly and show differences according to organs of origin. Novel technologies such as next-generation sequencing revealed new molecular aspects of NET over the last years. Notably, whole-exome/genome sequencing (WES/WGS) approaches underlined the very low mutation rate of well-differentiated NET of all organs compared to other malignancies, while the engagement of epigenetic changes in driving NET evolution is emerging. Indeed, mutations in genes encoding for proteins directly involved in chromatin remodelling, such as DAXX and ATRX are a frequent event in NET. Epigenetic changes are reversible and targetable; therefore, an attractive target for treatment. The discovery of the mechanisms underlying the epigenetic changes and the implication on gene and miRNA expression in the different subgroups of NET may represent a crucial change in the diagnosis of this disease, reveal new therapy targets and identify predictive markers. Molecular profiles derived from omics data including DNA mutation, methylation, gene and miRNA expression have already shown promising results in distinguishing clinically and molecularly different subtypes of NET. In this review, we recapitulate the major genetic and epigenetic characteristics of pancreatic, lung and small intestinal NET and the affected pathways. We also discuss potential epigenetic mechanisms leading to NET development.

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Section: :9mentioning

confidence: 99%

Genetic and epigenetic drivers of neuroendocrine tumours (NET)

Domenico

Wiedmer

Perren

2017

Endocrine-Related Cancer

106

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“…NF1 patients with GISTs tend to present at a younger age (median age 50 years) than sporadic cases (median age 55 to 65 years) [67]. The male:female ratio varies from 0.9:1 to 1:1.4 in different studies [55,56,58,68].…”

Section: Gastrointestinal Stromal Tumormentioning

confidence: 99%

Neoplasms Associated with Germline and Somatic NF1 Gene Mutations

2012

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After completing this course, the reader will be able to:1. Describe phenotypic and clinical features associated with neurofibromatosis 1. Identify malignant tumors associated with neurofibromatosis 1.This article is available for continuing medical education credit at CME.TheOncologist.com. CME CME ABSTRACTIntroduction. Neurofibromatosis 1 is a tumor predisposition genetic syndrome with autosomal dominant inheritance and virtually 100% penetrance by the age of 5 years. NF1 results from a loss-of-function mutation in the NF1 gene, resulting in decreased levels of neurofibromin in the cell. Neurofibromin is a negative regulator of various intracellular signaling pathways involved in the cellular proliferation. Although the loss of heterozygosity in the NF1 gene may predispose NF1 patients to certain malignancies, additional genetic alterations are a prerequisite for their development. The precise nature of these additional genetic alterations is not well defined, and genetic testing of all malignancies in NF1 patients becomes an essential component of future research in this subset of patients. In addition to germline NF1 mutations, alteration of the somatic NF1 gene is associated

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“…In a study from a large specialized centre, intra-abdominal (gastrointestinal or retroperitoneal) manifestations necessitating surgical intervention occurred in 2.5% of patients, at a median age of 40 years, followed up regularly [3,4]. NF1 patients may be predisposed to developing small intestinal GISTs, which may appear as multiple GISTs [5].…”

Section: Discussionmentioning

confidence: 99%

Case report of unusual cause of lower GI bleeding

AlHadhrami¹,

Al-Harthi²,

Elkak³

2016

Glob Surg

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Lower GI bleeding is a challenging emergency for the gastroenterologist and the surgeon especially when it is massive and obscure in origin. We present a case of a 41 years old male who presented to our hospital with lower GI bleeding which was massive and of unknown origin. It necessitated taking the patient for surgical intervention. The patient was found to have a bleeding gastrointestinal stromal tumor (GIST) in the small bowel. Small bowels GISTs are rare and unusual to present with lower GI bleeding. Case summary41 years old gentleman known to have neurofibromatosis type 1 who, in the past, underwent surgery of frontal brain lobe xanthoastrocytoma presented to the local hospital with massive rectal bleeding where he was resuscitated and referred to our center for further investigations and management. The patient was haemodynamyically reasonably stable when he was received in our centre with a hemoglobin of 9 g/dL, He continued to have rectal bleeding and an urgent upper gastrointestinal endoscopy and colonoscopy was arranged which did not identify the source of bleeding. Abdomen CT angiogram and then a mesenteric CT angiogram were performed but neither showed active contrast extravasation which could explain the source of bleeding. The CT showed extensive cutaneous and subcutaneous neurofibromatosis and left iliacus neurofibromatosis. The patient was kept on a high dependency unit where he received further 2 units of blood and his haemoglobin was stable around 9 g/dl. However, he became restless and drowsy and so he was intubated that stage and shifted to intensive care where he received further 2 units of blood and his haemoglobin did rise marginally from 8 g/dL to 8.2/dL, He continued to be off inotropes but tachycardic >110. So, the patient continued to pass P.R bleeding and was decided to be taken for surgical control. At laparotomy, there was a fairly vascular small bowel tumor 50 cm from ileocecal junction with no intraluminal blood distal to it. Another smaller one tumor was found just proximal to the first one (Figure 1). The first tumor was segmentally resected and continuity of the bowel was restored with side to side hand sewn anastomosis whilst the second tumor was locally excised. The patient remained stable in the postoperative period and made a swift recovery so he was discharged home after 5 days and seen in the clinic and found to have no complains. The Histopathology of the resected tumors came back as gastrointestinal stromal tumor (GIST) low malignant potential. With good margins > 5 cm free of the disease. Then the Patient was referred to medical oncologist for further input. He was seen after 2 months from the surgery in the medical oncology with a CT of chest, abdomen and pelvis which was normal and started on imatinib and he still in Follow-up with them. DiscussionThere is a cohort of causes of lower GI bleeding which had been described in the medical literature (Table 1). These causes may vary with the age and other associated conditions. Our patient was a known case of ne...

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Gastrointestinal and Retroperitoneal Manifestations of Type 1 Neurofibromatosis

Cited by 65 publications

References 57 publications

Genetic and epigenetic drivers of neuroendocrine tumours (NET)

Genetic and epigenetic drivers of neuroendocrine tumours (NET)

Neoplasms Associated with Germline and Somatic NF1 Gene Mutations

Case report of unusual cause of lower GI bleeding

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