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The Korean Journal of Gastroenterology... Jul 2017Cystic lesions of the pancreas are increasingly observed due to increased use of abdominal images. The malignant rate of pancreas cystic lesion varies widely between... (Review)
Review
Cystic lesions of the pancreas are increasingly observed due to increased use of abdominal images. The malignant rate of pancreas cystic lesion varies widely between various types. Identification of malignant or high-risk lesions is important when determining the appropriate course of management. Using these image findings, including cyst size, presence of solid components, and pancreatic duct involvement, the 2012 International Association of Pancreatology (IAP) and the 2015 American Gastroenterological Association (AGA) guidelines provide a rationale in identifying higher risk patients requiring further workups using an endoscopic ultrasound (EUS). EUS with fine needle aspiration and cytology allows confirmation of the cyst type and determines the risk of malignancy. Small cysts with no suspicious features may undergo the regular imaging study for regular surveillance due to low risk for malignancy. In this review, the differences between the 2012 IAP and 2015 AGA guidelines are presented, In addition to possible recommendations for management and surveillance.
Topics: Endosonography; Humans; Outpatients; Pancreatic Cyst; Pancreatic Neoplasms; Tomography, X-Ray Computed
PubMed: 28728311
DOI: 10.4166/kjg.2017.70.1.13 -
Acta Neuropathologica Mar 2012Neurofibromas, schwannomas and malignant peripheral nerve sheath tumors (MPNSTs) all arise from the Schwann cell lineage. Despite their common origin, these tumor types... (Review)
Review
Neurofibromas, schwannomas and malignant peripheral nerve sheath tumors (MPNSTs) all arise from the Schwann cell lineage. Despite their common origin, these tumor types have distinct pathologies and clinical behaviors; a growing body of evidence indicates that they also arise via distinct pathogenic mechanisms. Identification of the genes that are mutated in genetic diseases characterized by the development of either neurofibromas and MPNSTs [neurofibromatosis type 1 (NF1)] or schwannomas [neurofibromatosis type 2 (NF2), schwannomatosis and Carney complex type 1] has greatly advanced our understanding of these mechanisms. The development of genetically engineered mice with ablation of NF1, NF2, SMARCB1/INI1 or PRKAR1A has confirmed the key role these genes play in peripheral nerve sheath tumorigenesis. Establishing the functions of the NF1, NF2, SMARCB1/INI1 and PRKAR1A gene products has led to the identification of key cytoplasmic signaling pathways promoting Schwann cell neoplasia and identified new therapeutic targets. Analyses of human neoplasms and genetically engineered mouse models have established that interactions with other tumor suppressors such as TP53 and CDKN2A promote neurofibroma-MPNST progression and indicate that intratumoral interactions between neoplastic and non-neoplastic cell types play an essential role in peripheral nerve sheath tumorigenesis. Recent advances have also provided new insights into the identity of the neural crest-derived populations that give rise to different types of peripheral nerve sheath tumors. Based on these findings, we now have an initial outline of the molecular mechanisms driving the pathogenesis of neurofibromas, MPNSTs and schwannomas. However, this improved understanding in turn raises a host of intriguing new questions.
Topics: Cell Transformation, Neoplastic; Humans; Nerve Sheath Neoplasms; Neurilemmoma; Neurofibromatoses; Schwann Cells
PubMed: 22160322
DOI: 10.1007/s00401-011-0928-6 -
World Journal of Gastroenterology Jun 2019Technological advances and the widespread use of medical imaging have led to an increase in the identification of pancreatic cysts in patients who undergo... (Review)
Review
Technological advances and the widespread use of medical imaging have led to an increase in the identification of pancreatic cysts in patients who undergo cross-sectional imaging. Current methods for the diagnosis and risk-stratification of pancreatic cysts are suboptimal, resulting in both unnecessary surgical resection and overlooked cases of neoplasia. Accurate diagnosis is crucial for guiding how a pancreatic cyst is managed, whether with surveillance for low-risk lesions or surgical resection for high-risk lesions. This review aims to summarize the current literature on confocal endomicroscopy and cyst fluid molecular analysis for the evaluation of pancreatic cysts. These recent technologies are promising adjuncts to existing approaches with the potential to improve diagnostic accuracy and ultimately patient outcomes.
Topics: Biomarkers; Cyst Fluid; Diagnosis, Differential; Endoscopy; Humans; Intravital Microscopy; Microscopy, Confocal; Pancreas; Pancreatic Cyst; Pancreatic Neoplasms; Watchful Waiting
PubMed: 31235996
DOI: 10.3748/wjg.v25.i22.2734 -
Biochimica Et Biophysica Acta. Reviews... Apr 2017The mutational heterogeneity observed within tumours poses additional challenges to the development of effective cancer treatments. A thorough understanding of a... (Review)
Review
The mutational heterogeneity observed within tumours poses additional challenges to the development of effective cancer treatments. A thorough understanding of a tumour's subclonal composition and its mutational history is essential to open up the design of treatments tailored to individual patients. Comparative studies on a large number of tumours permit the identification of mutational patterns which may refine forecasts of cancer progression, response to treatment and metastatic potential. The composition of tumours is shaped by evolutionary processes. Recent advances in next-generation sequencing offer the possibility to analyse the evolutionary history and accompanying heterogeneity of tumours at an unprecedented resolution, by sequencing single cells. New computational challenges arise when moving from bulk to single-cell sequencing data, leading to the development of novel modelling frameworks. In this review, we present the state of the art methods for understanding the phylogeny encoded in bulk or single-cell sequencing data, and highlight future directions for developing more comprehensive and informative pictures of tumour evolution. This article is part of a Special Issue entitled: Evolutionary principles - heterogeneity in cancer?, edited by Dr. Robert A. Gatenby.
Topics: Adaptation, Physiological; Animals; Biomarkers, Tumor; Cell Transformation, Neoplastic; Evolution, Molecular; Gene Expression Regulation, Neoplastic; Genetic Fitness; Genetic Heterogeneity; Genetic Predisposition to Disease; Heredity; Humans; Models, Genetic; Mutation; Neoplasms; Pedigree; Phenotype; Phylogeny; Sequence Analysis, DNA; Signal Transduction; Single-Cell Analysis; Time Factors
PubMed: 28193548
DOI: 10.1016/j.bbcan.2017.02.001 -
RoFo : Fortschritte Auf Dem Gebiete Der... Dec 2015Neurofibromatosis type 1 (NF1) is a neurogenetic disorder. Individuals with NF1 may develop a variety of benign and malignant tumors of which peripheral nerve sheath... (Review)
Review
UNLABELLED
Neurofibromatosis type 1 (NF1) is a neurogenetic disorder. Individuals with NF1 may develop a variety of benign and malignant tumors of which peripheral nerve sheath tumors represent the most frequent entity. Plexiform neurofibromas may demonstrate a locally destructive growth pattern, may cause severe symptoms and may undergo malignant transformation into malignant peripheral nerve sheath tumors (MPNSTs). Whole-body magnetic resonance imaging (MRI) represents the reference standard for detection of soft tissue tumors in NF1. It allows for identification of individuals with plexiform neurofibromas, for assessment of local tumor extent, and for evaluation of whole-body tumor burden on T2-weighted imaging. Multiparametric MRI may provide a comprehensive characterization of different tissue properties of peripheral nerve sheath tumors, and may identify parameters associated with malignant transformation. Due to the absence of any radiation exposure, whole-body MRI may be used for serial follow-up of individuals with plexiform neurofibromas. (18)F-fluorodeoxyglucose positron-emission-tomography (FDG PET/CT) allows a highly sensitive and specific detection of MPNST, and should be used in case of potential malignant transformation of a peripheral nerve sheath tumor. PET/CT provides a sensitive whole-body tumor staging. The use of contrast-enhanced CT for diagnosis of peripheral nerve sheath tumors is limited to special indications. To obtain the most precise readings, optimized examination protocols and dedicated radiologists and nuclear medicine physicians familiar with the complex and variable morphologies of peripheral nerve sheath tumors are required.
KEY POINTS
Individuals with NF1 may develop benign and malignant nerve sheath tumors. Whole-body MRI is the reference standard to identify nerve sheath tumors in NF1. MRI provides a comprehensive characterization of the growth pattern, growth dynamics and extent of nerve sheath tumors. (18)F-FDG PET/CT provides a sensitivity of 100% and a specificity of 77-95% for detection of malignant transformation.
Topics: Adult; Cell Transformation, Neoplastic; Child; Diagnosis, Differential; Fluorodeoxyglucose F18; Humans; Magnetic Resonance Imaging; Multimodal Imaging; Nerve Sheath Neoplasms; Neurofibromatosis 1; Peripheral Nervous System Neoplasms; Positron-Emission Tomography; Sensitivity and Specificity; Soft Tissue Neoplasms; Tomography, X-Ray Computed; Whole Body Imaging; Young Adult
PubMed: 26333104
DOI: 10.1055/s-0035-1553505 -
Journal of the National Cancer Institute Sep 2013Many solid tumors, including pheochromocytoma (PHEO) and paraganglioma (PGL), are characterized by a (pseudo)hypoxic signature. (Pseudo)hypoxia has been shown to promote... (Review)
Review
Many solid tumors, including pheochromocytoma (PHEO) and paraganglioma (PGL), are characterized by a (pseudo)hypoxic signature. (Pseudo)hypoxia has been shown to promote both tumor progression and resistance to therapy. The major mediators of the transcriptional hypoxic response are hypoxia-inducible factors (HIFs). High levels of HIFs lead to transcription of hypoxia-responsive genes, which are involved in tumorigenesis. PHEOs and PGLs are catecholamine-producing tumors arising from sympathetic- or parasympathetic-derived chromaffin tissue. In recent years, substantial progress has been made in understanding the metabolic disturbances present in PHEO and PGL, especially because of the identification of some disease-susceptibility genes. To date, fifteen PHEO and PGL susceptibility genes have been identified. Based on the main transcription signatures of the mutated genes, PHEOs and PGLs have been divided into two clusters, pseudohypoxic cluster 1 and cluster 2, rich in kinase receptor signaling and protein translation pathways. Although these two clusters seem to show distinct signaling pathways, recent data suggest that both clusters are interconnected by HIF signaling as the important driver in their tumorigenesis, and mutations in most PHEO and PGL susceptibility genes seem to affect HIF-α regulation and its downstream signaling pathways. HIF signaling appears to play an important role in the development and growth of PHEOs and PGLs, which could suggest new therapeutic approaches for the treatment of these tumors.
Topics: Adrenal Gland Neoplasms; Animals; Basic Helix-Loop-Helix Transcription Factors; Cell Hypoxia; Gene Expression Regulation, Neoplastic; Humans; Hypoxia-Inducible Factor 1; Hypoxia-Inducible Factor 1, alpha Subunit; Multiple Endocrine Neoplasia Type 2a; Mutation; Neurofibromatosis 1; Paraganglioma; Pheochromocytoma; Signal Transduction; Up-Regulation; von Hippel-Lindau Disease
PubMed: 23940289
DOI: 10.1093/jnci/djt201 -
Actas Dermo-sifiliograficas Sep 2017Neurofibromatosis type 2 is an autosomal dominant hereditary disease with complete penetrance. It gives rise to multiple central and peripheral nervous system tumors,... (Review)
Review
Neurofibromatosis type 2 is an autosomal dominant hereditary disease with complete penetrance. It gives rise to multiple central and peripheral nervous system tumors, ocular alterations, and various types of skin lesion. In general, neither dermatologists nor other specialists have in-depth knowledge of the clinical manifestations of neurofibromatosis type 2. In some cases, this can lead to delayed diagnosis, which can increase morbidity and mortality. We describe the less well known clinical manifestations of NF2, focusing particularly on skin lesions specific to this disease. Identification of these lesions, when present, can facilitate diagnosis.
Topics: Cafe-au-Lait Spots; Cataract; Child; Early Diagnosis; Genes, Neurofibromatosis 2; Humans; Hyperpigmentation; Hypertrichosis; Molecular Diagnostic Techniques; Neurilemmoma; Neurofibromatosis 2; Neuroma, Acoustic; Prognosis; Skin; Skin Diseases
PubMed: 28237041
DOI: 10.1016/j.ad.2016.12.007 -
Child's Nervous System : ChNS :... Jan 2023Sylvian arachnoid cysts (SACs) are the most common type of arachnoid cysts and the most prone to undergo a rupture. This event is considered rare but potentially severe.... (Review)
Review
PURPOSE
Sylvian arachnoid cysts (SACs) are the most common type of arachnoid cysts and the most prone to undergo a rupture. This event is considered rare but potentially severe. No definite information is available on its occurrence or management. The goal of the present article is to provide an update on the epidemiological, etiological, and clinical aspects and the management of this peculiar clinical condition.
METHODS
A comprehensive review of the English literature of the last 40 years on this topic has been realized. Moreover, a personal series of children investigated and treated in the last 20 years is presented. These patients were managed as follows: (1) treatment of the subdural collection; (2) identification of candidates for surgical treatment of the residual cyst (brain MRI, perfusion brain MRI, prolonged invasive ICP monitoring (selected cases), EEG, neuropsychological tests); (3) surgical treatment of the cyst in the patients with pathological perfusion MRI and/or ICP measurement and/or clear neurophysiological and neuropsychological correlations.
RESULTS
A total of 446 patients (430 from the literature and 16 from the personal series), mainly children, adolescents, and young adults, have been analyzed leading to the following results: (1) SAC rupture is rare but not negligible (yearly risk of rupture: 0.04%; overall risk up to 10% in children affected by SCAs). Prophylactic surgery in asymptomatic cases is not advisable. (2) The mechanism of rupture is not known but an impact of SAC against the sphenoid wing and/or a direct injury on SAC through a thinned temporal bone, with possible laceration of the cyst wall vessels and/or tear of the bridging veins, can be hypothesized. A head injury is often not reported (may be misdiagnosed). (3) Subdural collection (hygroma > chronic hematoma) is the most common finding followed by intracystic bleeding, extradural hematoma, and other types of bleeding. Signs or symptoms of raised intracranial pressure are the most frequent ones. (4) The complication of the rupture is usually treated in emergency or in the acute period by burr hole or craniotomic evacuation of the subdural collection, although a conservative management is possible in some cases. Following the rupture, the majority of SACs are treated (70%), often at the same time of the complication, but no specific investigations are routinely performed to select candidates. According to our protocol, only 43.7% of SACs needed to be treated.
CONCLUSIONS
The "spontaneous" or posttraumatic rupture of SACs is a rare but potentially significant complication followed by a generally good outcome. The course of the cyst is independent from the outcome of the complication, consequently requiring specific investigations for individuating those lesions interfering with CSF dynamics and/or cerebral blood flow.
Topics: Child; Adolescent; Humans; Arachnoid Cysts; Rupture; Magnetic Resonance Imaging; Craniocerebral Trauma; Hematoma
PubMed: 36169701
DOI: 10.1007/s00381-022-05685-3 -
JAMA Oncology Apr 2023Sexual orientation and gender identity data are not collected by most hospitals or cancer registries; thus, little is known about the quality of breast cancer treatment...
IMPORTANCE
Sexual orientation and gender identity data are not collected by most hospitals or cancer registries; thus, little is known about the quality of breast cancer treatment for patients from sex and gender minority (SGM) groups.
OBJECTIVE
To evaluate the quality of breast cancer treatment and recurrence outcomes for patients from SGM groups compared with cisgender heterosexual patients.
DESIGN, SETTING, AND PARTICIPANTS
Exposure-matched retrospective case-control study of 92 patients from SGM groups treated at an academic medical center from January 1, 2008, to January 1, 2022, matched to cisgender heterosexual patients with breast cancer by year of diagnosis, age, tumor stage, estrogen receptor status, and ERBB2 (HER2) status.
MAIN OUTCOMES AND MEASURES
Patient demographic and clinical characteristics, as well as treatment quality, as measured by missed guideline-based breast cancer screening, appropriate referral for genetic counseling and testing, mastectomy vs lumpectomy, receipt of chest reconstruction, adjuvant radiation therapy after lumpectomy, neoadjuvant chemotherapy for stage III disease, antiestrogen therapy for at least 5 years for estrogen receptor-positive disease, ERBB2-directed therapy for ERBB2-positive disease, patient refusal of an oncologist-recommended treatment, time from symptom onset to tissue diagnosis, time from diagnosis to first treatment, and time from breast cancer diagnosis to first recurrence. Results were adjusted for multiple hypothesis testing. Compared with cisgender heterosexual patients, those from SGM groups were hypothesized to have disparities in 1 or more of these quality metrics.
RESULTS
Ninety-two patients from SGM groups were matched to 92 cisgender heterosexual patients (n = 184). The median age at diagnosis for all patients was 49 years (IQR, 43-56 years); 74 were lesbian (80%), 12 were bisexual (13%), and 6 were transgender (6%). Compared with cisgender heterosexual patients, those from SGM groups experienced a delay in time from symptom onset to diagnosis (median time to diagnosis, 34 vs 64 days; multivariable adjusted hazard ratio, 0.65; 95% CI, 0.42-0.99; P = .04), were more likely to decline an oncologist-recommended treatment modality (35 [38%] vs 18 [20%]; multivariable adjusted odds ratio, 2.27; 95% CI, 1.09-4.74; P = .03), and were more likely to experience a breast cancer recurrence (multivariable adjusted hazard ratio, 3.07; 95% CI, 1.56-6.03; P = .001).
CONCLUSIONS AND RELEVANCE
This study found that among patients with breast cancer, those from SGM groups experienced delayed diagnosis, with faster recurrence at a 3-fold higher rate compared with cisgender heterosexual patients. These results suggest disparities in the care of patients from SGM groups and warrant further study to inform interventions.
Topics: Humans; Female; Male; Adult; Middle Aged; Gender Identity; Breast Neoplasms; Retrospective Studies; Case-Control Studies; Receptors, Estrogen; Mastectomy; Neoplasm Recurrence, Local; Sexual and Gender Minorities; Sexual Behavior
PubMed: 36729432
DOI: 10.1001/jamaoncol.2022.7146 -
PloS One 2023Choledochal cysts (CC) are congenital bile duct anomalies with 6-30% risk for developing bile duct cancer. However, the molecular mechanisms underlying cancer risk of CC...
BACKGROUND
Choledochal cysts (CC) are congenital bile duct anomalies with 6-30% risk for developing bile duct cancer. However, the molecular mechanisms underlying cancer risk of CC are unknown. We sought to identify the gene expression changes underlying the cancer risk of CC patients.
METHODS
Liver organoids (n = 51) were generated from liver/bile duct biopsies of CC (n = 7; type I) and hepatoblastoma (n = 5; HB: non-tumor & tumor) for RNA sequencing. Bioinformatics analysis was conducted to identify differentially expressed cancer-related genes in CC and controls. We compared CC with non-cancerous and cancerous controls, normal adjacent non-tumor region of hepatoblastoma (HB) liver as non-cancerous control and tumor region as non-CC cancer control (HB-tumor). Reverse transcription real-time quantitative PCR (RT-qPCR) verification and immunohistochemistry of selected genes was conducted in additional CC and HB liver biopsies.
FINDINGS
HB non-tumor and HB tumor organoids displayed distinct gene expression profiles. Expression profiling separated CC organoids into two clusters, one overlapping with HB non-tumor and the other one with HB tumor organoids. Genes selected based on their log2FoldChange values for RT-qPCR verification in 31 CC and 11 HB non-tumor liver tissues revealed significantly elevated expression of FGFR2 in 7 and CEBPB in 2 CC liver tissues (CC vs HB: 4.082 vs. 0.7671, p<0.01; 2.506 vs. 1.210, p<0.01). Distinctive positive staining in bile ducts were seen in CC, HB tumor and non-tumor liver tissues for FGFR2 and CEBPB. Percentages of CEBPB-immuno-positive or FGFR2-immuno-positive bile duct cells in CC and HB-tumor liver were higher than that in HB non-tumor liver.
INTERPRETATION
The study identified dysregulated genes related to cancer pathways in CC patients suggesting cancer risk. The findings suggest that the elevated expression of FGFR2 and CEBPB in liver may contribute to cancer development in CC patients.
Topics: Humans; Choledochal Cyst; Hepatoblastoma; Bile Duct Neoplasms; Liver Neoplasms; Bile Ducts, Intrahepatic; Organoids; Sequence Analysis, RNA; Receptor, Fibroblast Growth Factor, Type 2; CCAAT-Enhancer-Binding Protein-beta
PubMed: 36996081
DOI: 10.1371/journal.pone.0283737