Natural history of renal tumours in von Hippel-Lindau disease: a large retrospective study of Chinese patients

BackgroundHistorically, renal cell carcinoma (RCC) is one of the main causes of death in von Hippel-Lindau (VHL) disease. However, the natural history of VHL-related RCC has not been thoroughly elucidated to date. This report described the natural history of VHL-related RCC in a large Chinese VHL cohort and might be helpful in the surveillance and treatment of VHL disease.MethodsIn this retrospective study, we included 196 renal tumours from 150 patients with VHL disease. Statistical analysis was used to evaluate the influence of age of onset, sex, family history, unilateral or bilateral tumour, VHL disease type, mutation type, mutation location, and tumour size on tumour growth, metastasis and survival in patients with VHL disease.ResultsThe mean age of onset was 38.8 years, and the mean initial tumour size was 3.1 cm. The mean linear growth rate was 0.49 cm/year. Patients experienced faster tumour growth when they had later age of onset, larger initial tumour size, missense mutation, mutations locating in exon 3, and when they were not affected by cerebral or retinal haemangioblastomas. Tumours larger than 4 cm grew faster than those smaller than 4 cm. Bilateral tumours, large initial tumours, fast tumour growth and metastasis were risk factors for poor prognosis in VHL-related RCC.ConclusionThis large study demonstrated that age of onset, initial tumour size, concomitant tumours, mutation type and mutation location had an effect on growth rate in VHL-related RCC. Active surveillance may be safe for patients with tumour size less than 4 cm, which is helpful in clinical decision-making.

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von Hippel-Lindau Disease: an Update

Current Genetic Medicine Reports ◽

10.1007/s40142-019-00180-9 ◽

2019 ◽

Vol 7 (4) ◽

pp. 227-235 ◽

Cited By ~ 2

Author(s):

Eamonn R Maher ◽

Richard N Sandford

Keyword(s):

Natural History ◽

Patient Outcomes ◽

Molecular Characterisation ◽

Von Hippel Lindau ◽

Functional Characterisation ◽

History Of ◽

Vhl Protein ◽

Von Hippel Lindau Disease ◽

Vhl Disease ◽

Improve Patient

Abstract Purpose of Review In this review, we discuss the key molecular and clinical developments in VHL disease that have the potential to impact on the natural history of the disease and improve patient outcomes. Recent Findings Identifiable mutations in VHL underlie most cases of VHL and define clear genotype-phenotype correlations. Detailed clinical and molecular characterisation has allowed the implementation of lifelong screening programmes that have improved clinical outcomes. Functional characterisation of the VHL protein complex has revealed its role in oxygen sensing and the mechanisms of tumourigenesis that are now being exploited to develop novel therapies for VHL and renal cancer. Summary The molecular and cellular landscape of VHL-associated tumours is revealing new opportunities to modify the natural history of the disease and develop therapies. Drugs are now entering clinical trials and combined with improved clinical and molecular diagnosis, and lifelong surveillance programmes, further progress towards reducing the morbidity and mortality associated with VHL disease is anticipated.

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The natural history of hemangioblastomas of the central nervous system in patients with von Hippel—Lindau disease

Journal of Neurosurgery ◽

10.3171/jns.2003.98.1.0082 ◽

2003 ◽

Vol 98 (1) ◽

pp. 82-94 ◽

Cited By ~ 276

Author(s):

John E. Wanebo ◽

Russell R. Lonser ◽

Gladys M. Glenn ◽

Edward H. Oldfield

Keyword(s):

Spinal Cord ◽

Natural History ◽

Mass Effect ◽

Content Type ◽

Von Hippel Lindau ◽

History Of ◽

The Central Nervous System ◽

Brainstem Tumors ◽

Vhl Disease ◽

Fine Print

Object. The goals of this study were to define the natural history and growth pattern of hemangioblastomas of the central nervous system (CNS) that are associated with von Hippel—Lindau (VHL) disease and to correlate features of hemangioblastomas that are associated with the development of symptoms and the need for treatment. Methods. The authors reviewed serial magnetic resonance images and clinical histories of 160 consecutive patients with VHL disease who harbored CNS hemangioblastomas and serially measured the volumes of tumors and associated cysts. Six hundred fifty-five hemangioblastomas were identified in the cerebellum (250 tumors), brainstem (64 tumors, all of which were located in the posterior medulla oblongata), spinal cord (331 tumors, 96% of which were located in the posterior half of spinal cord), and the supratentorial brain (10 tumors). The symptoms were related to a mass effect. A serial increase in hemangioblastoma size was observed in cerebellar, brainstem, and spinal cord tumors as patients progressed from being asymptomatic to symptomatic and requiring surgery (p < 0.0001). Twenty-one (72%) of 29 symptom-producing cerebellar tumors had an associated cyst, whereas only 28 (13%) of 221 nonsymptomatic cerebellar tumors had tumor-associated cysts (p < 0.0001). Nine (75%) of 12 symptomatic brainstem tumors had associated cysts, compared with only four (8%) of 52 nonsymptomatic brainstem lesions (p < 0.0001). By the time the symptoms appeared and surgery was required, the cyst was larger than the causative tumor; cerebellar and brainstem cysts measured 34 and 19 times the size of their associated tumors at surgery, respectively. Ninety-five percent of symptom-producing spinal hemangioblastomas were associated with syringomyelia. The clinical circumstance was dynamic. Among the 88 patients who had undergone serial imaging for 6 months or longer (median 32 months), 164 (44%) of 373 hemangioblastomas and 37 (67%) of 55 tumor-associated cysts enlarged. No tumors or cysts spontaneously diminished in size. Symptomatic cerebellar and brainstem tumors grew at rates six and nine times greater, respectively, than asymptomatic tumors in the same regions. Cysts enlarged seven (cerebellum) and 15 (brainstem) times faster than the hemangioblastomas causing them. Hemangioblastomas frequently demonstrated a pattern of growth in which they would enlarge for a period of time (growth phase) and then stabilize in a period of arrested growth (quiescent phase). Of 69 patients with documented tumor growth, 18 (26%) harbored tumors with at least two growth phases. Of 160 patients with hemangioblastomas, 34 patients (median follow up 51 months) were found to have 115 new hemangioblastomas and 15 patients new tumor-associated cysts. Conclusions. In this study the authors define the natural history of CNS hemangioblastomas associated with VHL disease. Not only were cysts commonly associated with cerebellar, brainstem, and spinal hemangioblastomas, the pace of enlargement was much faster for cysts than for hemangioblastomas. By the time symptoms appeared, the majority of mass effect—producing symptoms derived from the cyst, rather than from the tumor causing the cyst. These tumors often have multiple periods of tumor growth separated by periods of arrested growth, and many untreated tumors may remain the same size for several years. These characteristics must be considered when determining the optimal timing of screening for individual patients and for evaluating the timing and results of treatment.

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Revisiting the Natural History of Chronic Scaphoid Nonunions: A Retrospective Study of 20 Cases

Journal of Wrist Surgery ◽

10.1055/s-0040-1721435 ◽

2021 ◽

Author(s):

J. Terrence Jose Jerome

Keyword(s):

Retrospective Study ◽

Natural History ◽

Functional Outcome ◽

Grip Strength ◽

Scaphoid Nonunion ◽

Proximal Pole ◽

Degenerative Arthritis ◽

Level Of Evidence ◽

History Of ◽

The Mean

Abstract Background The natural history of scaphoid nonunion is the development of degenerative arthritis. A lot of information is still unclear about this progression. The purpose of this study is to analyze patients with scaphoid nonunions who had not received any kind of treatment and to assess the functional outcome. Materials and Methods This is a retrospective study that analyzed the patients with chronic scaphoid nonunions between 2009 and 2019. None of the patients received any treatment. The age at the time of injury, examination, pattern of fracture, types of scaphoid nonunion, symptoms, and duration of nonunion were noted. Diagnosis was confirmed by radiographs, computed tomography (CT) scan, and magnetic resonance imaging (MRI). Scapholunate and radiolunate angles were recorded. Pain score, modified mayo wrist score, grip strength, range of movement, and the functional outcome of these scaphoid nonunions were analyzed. A statistical correlation between the scaphoid nonunion presentations and the functional outcome was assessed. Results The mean age of the patients was 62 years (range: 35–82 years.). There were 17 male and 3 female patients. There were 9 waist and 11 proximal pole scaphoid nonunions. The mean duration of scaphoid nonunion was 34 years (range: 10–62 years). None of the patients had avascular necrosis (AVN) of the proximal scaphoid. The age at examination, gender, side of injury, fracture pattern (waist/proximal pole), fracture displacement ≤ 1 mm or > 1 mm, nonunion duration, and radiographic arthritic parameters had no significant impact on the functional outcome. Conclusions Untreated chronic scaphoid nonunion leads to the development of degenerative arthritis over a period of years, which is still unpredictable. Most of the patients become aware of the nonunion following a precedent injury or other reasons. Most of the patients have fair/good functional outcome despite reduced range of movements and grip strength. Many do not favor surgical intervention in the course of nonunion. Chronic nonunions open a lot of unanswered questions. Clinical relevance There have been numerous studies on the treatment aspects of scaphoid nonunion, with little knowledge about certain people with nonunion who did not have any kind of treatment. The demographics, clinical findings, and radiological parameters do confirm the progression of these nonunion to arthritis, but most of them had fair-to-good outcome throughout their life. It opens our thinking about the real need of treatment in such nonunions and raises numerous questions about the disease. Level of evidence This is a Level IV study.

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Biological and clinical impact of hemangioblastoma-associated peritumoral cysts in von Hippel-Lindau disease

Journal of Neurosurgery ◽

10.3171/2015.4.jns1533 ◽

2016 ◽

Vol 124 (4) ◽

pp. 971-976 ◽

Cited By ~ 17

Author(s):

Kristin Huntoon ◽

Tianxia Wu ◽

J. Bradley Elder ◽

John A. Butman ◽

Emily Y. Chew ◽

...

Keyword(s):

Clinical Impact ◽

Anatomical Location ◽

Von Hippel Lindau ◽

Study Enrollment ◽

Common Location ◽

Younger Age ◽

The Mean ◽

A Prospective Study ◽

Vhl Disease

OBJECT Peritumoral cysts are frequently associated with CNS hemangioblastomas and often underlie neurological morbidity and mortality. To determine their natural history and clinical impact, the authors prospectively analyzed hemangioblastoma-associated peritumoral cysts in patients with von Hippel-Lindau (VHL) disease. METHODS Patients with VHL disease who had 2 or more years of follow-up and who were enrolled in a prospective study at the National Institutes of Health were included. Serial prospectively acquired laboratory, genetic, imaging, and clinical data were analyzed. RESULTS One hundred thirty-two patients (of 225 in the VHL study with at least 2 years of follow-up) had peritumoral cysts that were followed for more than 2 years (total of 292 CNS peritumoral cysts). The mean age at study entrance was 37.4 ± 13.1 years ([mean ± SD], median 37.9, range 12.3–65.1 years). The mean follow-up was 7.0 ± 1.7 years (median 7.3, range 2.1–9.0 years). Over the study period, 121 of the 292 peritumoral cysts (41.4%) became symptomatic. Development of new cysts was associated with a larger number cysts at study enrollment (p = 0.002) and younger age (p < 0.0001). Cyst growth rate was associated with anatomical location (cerebellum cysts grew faster than spine and brainstem cysts; p = 0.0002 and p = 0.0008), younger age (< 35 years of age; p = 0.0006), and development of new neurological symptoms (p < 0.0001). Cyst size at symptom production depended on anatomical location (p < 0.0001; largest to smallest were found, successively, in the cerebellum, spinal cord, and brainstem). The most common location for peritumoral cysts was the cerebellum (184 cysts [63%]; p < 0.0001). CONCLUSIONS Peritumoral cysts frequently underlie symptom formation that requires surgical intervention in patients with VHL disease. Development of new cysts was associated with a larger number of cysts at study enrollment and younger age. Total peritumoral cyst burden was associated with germline partial deletion of the VHL gene.

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SOD1 Mutation Spectrum and Natural History of ALS Patients in a 15-Year Cohort in Southeastern China

Frontiers in Genetics ◽

10.3389/fgene.2021.746060 ◽

2021 ◽

Vol 12 ◽

Author(s):

Lu-Xi Chen ◽

Hai-Feng Xu ◽

Pei-Shan Wang ◽

Xin-Xia Yang ◽

Zhi-Ying Wu ◽

...

Keyword(s):

Clinical Trials ◽

Natural History ◽

Diagnostic Delay ◽

Mutation Spectrum ◽

Survival Duration ◽

Southeastern China ◽

History Of ◽

Male Patients ◽

The Mean ◽

Als Patients

Background: Mutations in superoxide dismutase 1 gene (SOD1) are the most frequent high penetrant genetic cause for amyotrophic lateral sclerosis (ALS) in the Chinese population. A detailed natural history of SOD1-mutated ALS patients will provide key information for ongoing genetic clinical trials.Methods: We screened for SOD1 mutations using whole exome sequencing (WES) in Chinese ALS cases from 2017 to 2021. Functional studies were then performed to confirm the pathogenicity of novel variants. In addition, we enrolled previously reported SOD1 mutations in our centers from 2007 to 2017. The SOD1 mutation spectrum, age at onset (AAO), diagnostic delay, and survival duration were analyzed.Results: We found two novel SOD1 variants (p.G17H and p.E134*) that exerted both gain-of-function and loss-of-function effects in vitro. Combined with our previous SOD1-mutated patients, 32 probands with 21 SOD1 mutations were included with the four most frequently occurring mutations of p.V48A, p.H47R, p.C112Y, and p.G148D. SOD1 mutations account for 58.9% of familial ALS (FALS) cases. The mean (SD) AAO was 46 ± 11.4 years with a significant difference between patients carrying mutations in exon 1 [n = 5, 34.6 (12.4) years] and exon 2 [n = 8, 51.4 (8.2) years] (p = 0.038). The mean of the diagnostic delay of FALS patients is significantly earlier than the sporadic ALS (SALS) patients [9.5 (4.8) vs. 20.3 (9.3) years, p = 0.0026]. In addition, male patients survived longer than female patients (40 vs. 16 months, p = 0.05).Conclusion: Our results expanded the spectrum of SOD1 mutations, highlighted the mutation distribution, and summarized the natural history of SOD1-mutated patients in southeastern China. Male patients were found to have better survival, and FALS patients received an earlier diagnosis. Our findings assist in providing a detailed clinical picture, which is important for ongoing genetic clinical trials.

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Clinical, epidemiological and autoimmune associations in childhood vitiligo in Qatar

International Journal of Research in Dermatology ◽

10.18203/issn.2455-4529.intjresdermatol20200594 ◽

2020 ◽

Vol 6 (2) ◽

pp. 151

Author(s):

Haya Al Mannai ◽

Mohamed Allam ◽

Hassan Riad

Keyword(s):

Family History ◽

Autoimmune Diseases ◽

Age Of Onset ◽

Positive Family History ◽

Thyroid Peroxidase ◽

Base Line ◽

Adult Onset ◽

Prognostic Features ◽

History Of ◽

The Mean

Background: Childhood vitiligo although clinically similar to adult onset vitiligo but it has distinct clinical, epidemiological and prognostic features compared to adult onset vitiligo.Methods: This is a retrospective study that was carried out on 85 pediatric patients up to age of 18 years old with the diagnosis of vitiligo, where the clinical and epidemiological data including clinical type of vitiligo, family history of autoimmune diseases like thyroid disorders and diabetes mellitus and laboratory results including anti-thyroid peroxidase antibodies (anti-TPO antibodies), anti-parietal cell antibodies, antinuclear antibodies (ANA), Vitamin D and Vitamin B12 were retrieved from the files of these patients.Results: The mean age of the children affected by vitiligo was 10.4 years, the mean age of onset of vitiligo was 5.4 years, 54 (63.5%) percent were girls and 31 (36.5%) were boys. A positive family history of vitiligo was found in 44.7% of the participants, family history of DM was found in 64.7% of patients and family history of thyroid disease was found in 32.9% of the participants. The prevalence of thyroid autoimmunity was found to be in 22.4% of total participants.Conclusions: Childhood vitiligo has distinct clinical features, more common family history for autoimmune diseases and thyroid autoantibodies rather than overt clinical diseases, which raise the necessity to perform a routine initial immunological and thyroid screening in children with vitiligo and to repeat them at annual bases if there were abnormal values at base line or strong family history.

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Epidemiology and associated factors of atopic dermatitis in Malagasy children

Allergy Asthma & Clinical Immunology ◽

10.1186/s13223-019-0398-2 ◽

2020 ◽

Vol 16 (1) ◽

Cited By ~ 1

Author(s):

F. A. Sendrasoa ◽

I. M. Ranaivo ◽

N. H. Razanakoto ◽

M. Andrianarison ◽

O. Raharolahy ◽

...

Keyword(s):

Atopic Dermatitis ◽

Low Income ◽

Rural Areas ◽

Associated Factors ◽

Age Of Onset ◽

Descriptive Study ◽

History Of ◽

The Mean ◽

Urban And Rural Areas ◽

Duration Of Breastfeeding

Abstract Background Little is known about the epidemiology and associated factors of childhood AD in the markedly different, low-income, tropical environment like Madagascar. Methods We aim to assess the epidemiology and associated factors of AD in individuals fewer than 15 years of age in Antananarivo Madagascar. It was a retrospective and descriptive study over a period of 7 years (2010 to 2016) in children 6 months to 14 years in the Department of Dermatology, Joseph Raseta Befelatanana Antananarivo Madagascar. The diagnosis of AD was based on clinical data. Results The prevalence of AD was 5.6% in children aged 6 months to 14 years. The details of 151 cases of atopic dermatitis were analyzed. The mean age of patients was 4 years. There was a female preponderance (sex ratio: 0.7). A family history of AD was noted in 56 cases (37%). No association between breast-feeding and AD was found. The age of onset of AD was before the age of 3 months in 7.5% and between 6 months to 5 years in 70%. Children born in March (dry season) had the highest risk of AD. Consultations for AD increased during the winter (from July to October; p = 0.005). However, the prevalence of AD was similar in urban and rural areas. Conclusion Weather may have an impact on the prevalence of atopic dermatitis in Madagascar. No significant correlation was found between the duration of breastfeeding and AD, as well as urbanization.

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A Family with Multiple Instances of Definite, Probable and Possible Early-Onset Alzheimer's Disease

The British Journal of Psychiatry ◽

10.1192/bjp.159.4.524 ◽

1991 ◽

Vol 159 (4) ◽

pp. 524-530 ◽

Cited By ~ 9

Author(s):

H. Karlinsky ◽

E. Madrick ◽

J. Ridgley ◽

J. M. Berg ◽

R. Becker ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Early Onset ◽

Age Of Onset ◽

Diagnostic Difficulties ◽

History Of ◽

Early Onset Alzheimer’S Disease ◽

The Mean ◽

Age Of Death

A family with a multigenerational history of proven or suspected early-onset Alzheimer's disease (AD) consistent with autosomal-dominant inheritance is described. To date, the pedigree comprises five generations in which there are 13 known affected individuals. The mean age of onset of cognitive deficits in those for whom data are available (n = 11) is 47.6 (s.d. 3.0) years and the mean age of death (n = 10) is 58.8 (s.d. 4.0) years. The variability in the extent and quality of available data illustrates the diagnostic difficulties encountered in ascertaining such an extended pedigree, and the need for caution in interpreting the evidence.

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The natural history of pineal cysts in children and young adults

Journal of Neurosurgery Pediatrics ◽

10.3171/2009.9.peds09297 ◽

2010 ◽

Vol 5 (2) ◽

pp. 162-166 ◽

Cited By ~ 45

Author(s):

Wajd N. Al-Holou ◽

Cormac O. Maher ◽

Karin M. Muraszko ◽

Hugh J. L. Garton

Keyword(s):

Natural History ◽

Mr Imaging ◽

Initial Study ◽

Older Children ◽

Imaging Evaluation ◽

Imaging Appearance ◽

Imaging Characteristics ◽

History Of ◽

The Mean

Object The authors reviewed their experience with pediatric pineal cysts to define the natural history and clinical relevance of this common intracranial finding. Methods The authors identified all patients with pineal cysts who had been clinically evaluated at their institution over an 11.5-year interval and were < 25 years of age at the time of diagnosis. All inclusion criteria were met in 106 patients, and included repeated MR imaging as well as repeated clinical evaluation over at least a 6-month interval. Results The mean age at diagnosis was 11.7 ± 7.2 years. Forty-two patients were male and 64 were female. On follow-up MR imaging evaluation at a mean interval of 3.0 years from the initial study, 98 pineal cysts had no increase in size and no change in imaging appearance. Six pineal cysts increased in size and 2 others had a change in imaging characteristics without associated growth. Younger age was associated with cyst change or growth on follow-up imaging (p = 0.02). The mean age of patients with cysts that changed or grew was 5.5 years, and the mean age of patients with stable pineal cysts was 12.2 years. Initial cyst size and appearance on MR imaging were not significant predictors of growth or change in imaging appearance at follow-up. Similarly, the patient's sex was not a significant predictor of growth or change in imaging characteristics. Conclusions Follow-up imaging and neurosurgical evaluation may be considered optional in older children with pineal cysts.

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