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Frontiers in Endocrinology 2024The 2022 World Health Organization (WHO) classification of pituitary neuroendocrine tumour (PitNET) supersedes the previous one in 2017 and further consolidates the role...
BACKGROUND
The 2022 World Health Organization (WHO) classification of pituitary neuroendocrine tumour (PitNET) supersedes the previous one in 2017 and further consolidates the role of transcription factors (TF) in the diagnosis of PitNET. Here, we investigated the clinical utility of the 2022 WHO classification, as compared to that of 2017, in a cohort of patients with non-functioning PitNET (NF-PitNET).
METHODS
A total of 113 NF-PitNET patients who underwent resection between 2010 and 2021, and had follow-up at Queen Mary Hospital, Hong Kong, were recruited. Surgical specimens were re-stained for the three TF: steroidogenic factor (SF-1), T-box family member TBX19 (TPIT) and POU class 1 homeobox 1 (Pit-1). The associations of different NF-PitNET subtypes with tumour-related outcomes were evaluated by logistic and Cox regression analyses.
RESULTS
Based on the 2022 WHO classification, the majority of NF-PitNET was SF-1-lineage tumours (58.4%), followed by TPIT-lineage tumours (18.6%), tumours with no distinct lineage (16.8%) and Pit-1-lineage tumours (6.2%). Despite fewer entities than the 2017 classification, significant differences in disease-free survival were present amongst these four subtypes (Log-rank test p=0.003), specifically between SF-1-lineage PitNET and PitNET without distinct lineage (Log-rank test p<0.001). In multivariable Cox regression analysis, the subtype of PitNET without distinct lineage (HR 3.02, 95% CI 1.28-7.16, p=0.012), together with tumour volume (HR 1.04, 95% CI 1.01-1.07, p=0.017), were independent predictors of a composite of residual or recurrent disease.
CONCLUSION
The 2022 WHO classification of PitNET is a clinically useful TF and lineage-based system for subtyping NF-PitNET with different tumour behaviour and prognosis.
Topics: Humans; World Health Organization; Female; Male; Middle Aged; Pituitary Neoplasms; Neuroendocrine Tumors; Adult; Aged; Prognosis; Young Adult; Follow-Up Studies; T-Box Domain Proteins
PubMed: 38756997
DOI: 10.3389/fendo.2024.1368944 -
Rare Tumors 2024Laryngeal schwannoma is a rare benign nerve sheath tumor that is slow growing. The diagnosis is made from a combination of clinical, radiological, and histopathological...
Laryngeal schwannoma is a rare benign nerve sheath tumor that is slow growing. The diagnosis is made from a combination of clinical, radiological, and histopathological findings, and the main method of treatment is resection. We report a case of a 69-year-old presenting with a neck mass causing stridor, dysphagia, and orthopnea. CT of the neck showed an enhancing mass measuring 6.3 cm and extending superior to the larynx. Emergent tracheostomy and mass resection were performed, and histopathology and immunohistochemical findings were obtained from the specimen supporting schwannoma. In conclusion, while rare, schwannoma should always be considered as a differential diagnosis for a laryngeal mass. More studies are needed to assess the size and prognosis of the tumor.
PubMed: 38756435
DOI: 10.1177/20363613241255669 -
JPGN Reports May 2024We report the case of a 14-year-old patient with a known history of Crohn's disease who was incidentally diagnosed with an asymptomatic cecal lipoma. A routine...
We report the case of a 14-year-old patient with a known history of Crohn's disease who was incidentally diagnosed with an asymptomatic cecal lipoma. A routine surveillance colonoscopy as part of the management of the patient's Crohn's Disease revealed a well-defined, submucosal, yellowish mass in the patient's cecum. Histopathological examination of a biopsy specimen revealed submucosal adipose tissue, consistent with the endoscopic images showing the characteristic appearance of the lipoma. A computed tomography examination further confirmed the diagnosis. While colonic lipomas are infrequent and typically manifest later in life, few cases report the coexistence of a cecal lipoma with Crohn's disease, particularly in the pediatric population. In this case, managing this dual condition posed a notable challenge. Here, we present the conservative approach to managing a pediatric patient with cecal lipoma and Crohn's disease. The decision to leave the lipoma in situ was based on the absence of symptoms and potential risks associated with surgical removal.
PubMed: 38756132
DOI: 10.1002/jpr3.12061 -
Journal of Neurological Surgery Reports Apr 2024Prolactinomas are a common intracranial neoplasm and constitute most pituitary tumors. Although patients can present with variable hormone dysregulation and symptom...
Prolactinomas are a common intracranial neoplasm and constitute most pituitary tumors. Although patients can present with variable hormone dysregulation and symptom severity, the use of dopamine agonists remains a first-line treatment. While bromocriptine has been found to increase tumor fibrosis, the effect of cabergoline on collagen deposition has been disputed. The aim of this article is to understand the influence of cabergoline on tumor fibrosis prior to resection. Four male patients who underwent prolactinoma resection were included in this report. The average age was 39.8 years (range: 26-52 years). Pre-treatment prolactin levels ranged from 957.8 to 16,487.4 ng/mL. Three patients received cabergoline for at least 1 month prior to surgery (treatment range: 1-6 months). One patient had surgery without prior cabergoline use. Pathology reports confirmed each tumor to be of lactotroph origin. For each sample, Masson's trichrome staining was performed and the percentage of sample fibrosis was quantified using an artificial intelligence imaging software. Among those who received preoperative cabergoline, the extent of tumor fibrosis was in the range of 50 to 70%. In contrast, specimen fibrosis was approximately 15% without cabergoline use. This report demonstrates that a short duration of preoperative cabergoline can cause significant prolactinoma fibrosis. Understanding the effect of cabergoline on tumor consistency prior to surgery is essential as increased fibrosis can lead to more difficult tumor removal, reduce the extent of resection, and increase surgical complications. Considering these effects, further studies regarding the use of surgery prior to cabergoline for prolactinoma management are warranted.
PubMed: 38751869
DOI: 10.1055/s-0044-1786740 -
Translational Breast Cancer Research :... 2023Breast cancer is a disease of global concern, regardless of economic status. A significant disparity in breast cancer care between low- and high-income countries is not... (Review)
Review
Breast cancer is a disease of global concern, regardless of economic status. A significant disparity in breast cancer care between low- and high-income countries is not unexpected, but consideration can be given to particular aspects of therapy to allow as much equitability as possible. One of these aspects involves biopsy of breast lesions. With available resources, management in developed countries focuses on dealing with screening and image-detected lesions. In such circumstances, advanced percutaneous biopsy techniques are utilized liberally. However, where resources are less forthcoming for mammographic screening, women frequently present with symptomatic, palpable and larger tumours. This scenario behooves the clinician to modify treatment approaches and yet use cost-effective management strategies. It is essential that thought is applied to breast biopsy technique used where there is cost-consciousness as it significantly influences subsequent therapy. Less expensive strategies like fine needle aspiration cytology (FNAC) and core needle biopsy (CNB), when performed with particular attention to technique, handling, transportation and preparation of biopsy specimens allows a high level of accuracy and provides adequate information for the next steps in treatment. This mini-review discusses the variation in biopsy approaches among lower and higher income areas and offers suggestions for appropriate breast biopsy strategies in resource-limited countries.
PubMed: 38751462
DOI: 10.21037/tbcr-23-12 -
Cellular and Molecular Gastroenterology... May 2024Hepatocellular carcinoma (HCC) is a heterogeneous cancer with varying levels of liver tumor initiating or cancer stem cells in the tumors. We aimed to investigate the...
BACKGROUND & AIMS
Hepatocellular carcinoma (HCC) is a heterogeneous cancer with varying levels of liver tumor initiating or cancer stem cells in the tumors. We aimed to investigate the expression of different liver cancer stem cell (LCSC) markers in human HCCs, and identify their regulatory mechanisms in stemness-related cells.
METHODS
We used an unbiased, single-marker sorting approach by flow cytometry, fluorescence-activated cell sorting, and transcriptomic analyses on HCC patients' resected specimens. Knockdown approach was employed and relevant functional assays were conducted on the identified targets of interest.
RESULTS
Flow cytometry on a total of 60 HCC resected specimens showed significant heterogeneity in the expression of LCSC markers, with CD24, CD13, and EpCAM mainly contributing to this heterogeneity. Concomitant expression of CD24, CD13 and EpCAM was detected in 32 HCC samples, and this was associated with advanced tumor stages. Transcriptomic sequencing on the HCC cells sorted for these individual markers identified EPS8L3 as a common gene associated with the three markers and was functionally validated in HCC cells. Knocking down EPS8L3 suppressed the expression of all three markers. To search for the upstream regulation of EPS8L3, we found SP1 bound to EPS8L3 promoter to drive EPS8L3 expression. Furthermore, using Akt inhibitor MK2206, we showed that Akt-signaling-driven SP1 drove the expression of the three LCSC markers CONCLUSIONS: Our findings suggest that Akt-signaling-driven SP1 promotes EPS8L3 expression, which is critical in maintaining the downstream expression of CD24, CD13 and EpCAM. The findings provide insight into potential LCSC-targeting therapeutic strategies.
PubMed: 38750898
DOI: 10.1016/j.jcmgh.2024.05.006 -
Molecular Neurodegeneration May 2024Alzheimer's disease (AD), the most common form of dementia, remains challenging to understand and treat despite decades of research and clinical investigation. This... (Review)
Review
Alzheimer's disease (AD), the most common form of dementia, remains challenging to understand and treat despite decades of research and clinical investigation. This might be partly due to a lack of widely available and cost-effective modalities for diagnosis and prognosis. Recently, the blood-based AD biomarker field has seen significant progress driven by technological advances, mainly improved analytical sensitivity and precision of the assays and measurement platforms. Several blood-based biomarkers have shown high potential for accurately detecting AD pathophysiology. As a result, there has been considerable interest in applying these biomarkers for diagnosis and prognosis, as surrogate metrics to investigate the impact of various covariates on AD pathophysiology and to accelerate AD therapeutic trials and monitor treatment effects. However, the lack of standardization of how blood samples and collected, processed, stored analyzed and reported can affect the reproducibility of these biomarker measurements, potentially hindering progress toward their widespread use in clinical and research settings. To help address these issues, we provide fundamental guidelines developed according to recent research findings on the impact of sample handling on blood biomarker measurements. These guidelines cover important considerations including study design, blood collection, blood processing, biobanking, biomarker measurement, and result reporting. Furthermore, the proposed guidelines include best practices for appropriate blood handling procedures for genetic and ribonucleic acid analyses. While we focus on the key blood-based AD biomarkers for the AT(N) criteria (e.g., amyloid-beta [Aβ]40, Aβ42, Aβ42/40 ratio, total-tau, phosphorylated-tau, neurofilament light chain, brain-derived tau and glial fibrillary acidic protein), we anticipate that these guidelines will generally be applicable to other types of blood biomarkers. We also anticipate that these guidelines will assist investigators in planning and executing biomarker research, enabling harmonization of sample handling to improve comparability across studies.
Topics: Humans; Alzheimer Disease; Biomarkers; Biological Specimen Banks; Research Design; Amyloid beta-Peptides; Specimen Handling; tau Proteins
PubMed: 38750570
DOI: 10.1186/s13024-024-00711-1 -
Magnetic Resonance in Medical Sciences... May 2024To investigate the predictive performance of radiomic features extracted from breast MRI for upgrade of ductal carcinoma in situ (DCIS) to invasive carcinoma.
PURPOSE
To investigate the predictive performance of radiomic features extracted from breast MRI for upgrade of ductal carcinoma in situ (DCIS) to invasive carcinoma.
METHODS
This retrospective study included 71 women with DCIS lesions diagnosed preoperatively by biopsy. All women underwent breast dynamic contrast-enhanced (DCE) MRI of the breast, which included pre-contrast and five post-contrast phases continuously with a time resolution of 60s. Lesion segmentation was performed manually, and 144 radiomic features of the lesions were extracted from T2-weighted images (T2WI), pre-contrast T1-weighted images (T1WI), and post-contrast 1st, 2nd, and 5th phase subtraction images on DCE-MRI. Qualitative features of mammography, ultrasound, and MRI were also assessed. Clinicopathological features were evaluated using medical records. The least absolute shrinkage and selection operator (LASSO) algorithm was applied for features selection and model building. The predictive performance of postoperative upgrade to invasive carcinoma was assessed using the area under the receiver operating characteristic curve.
RESULTS
Surgical specimens revealed 13 lesions (18.3%) that were upgraded to invasive carcinoma. Among clinicopathological and qualitative features, age was the only significant predictive variable. No significant radiomic features were observed on T2WI and post-contrast 2nd phase subtraction images on DCE-MRI. The area under the curves (AUCs) of the LASSO radiomics model integrated with age were 0.915 for pre-contrast T1WI, 0.862 for post-contrast 1st phase subtraction images, and 0.833 for post-contrast 5th phase subtraction images. The AUCs of the 200-times bootstrap internal validations were 0.885, 0.832, and 0.775.
CONCLUSION
A radiomics approach using breast MRI may be a promising method for predicting the postoperative upgrade of DCIS. The present study showed that the radiomic features extracted from pre-contrast T1WI and post-contrast subtraction images in the very early phase of DCE-MRI were more predictable.
PubMed: 38749758
DOI: 10.2463/mrms.mp.2023-0168 -
BMJ Open May 2024To estimate the shape of the causal relationship between body mass index (BMI) and mortality risk in a Mendelian randomisation framework.
OBJECTIVES
To estimate the shape of the causal relationship between body mass index (BMI) and mortality risk in a Mendelian randomisation framework.
DESIGN
Mendelian randomisation analyses of two prospective population-based cohorts.
SETTING
Individuals of European ancestries living in Norway or the UK.
PARTICIPANTS
56 150 participants from the Trøndelag Health Study (HUNT) in Norway and 366 385 participants from UK Biobank recruited by postal invitation.
OUTCOMES
All-cause mortality and cause-specific mortality (cardiovascular, cancer, non-cardiovascular non-cancer).
RESULTS
A previously published non-linear Mendelian randomisation analysis of these data using the residual stratification method suggested a J-shaped association between genetically predicted BMI and mortality outcomes with the lowest mortality risk at a BMI of around 25 kg/m. However, the 'constant genetic effect' assumption required by this method is violated. The reanalysis of these data using the more reliable doubly-ranked stratification method provided some indication of a J-shaped relationship, but with much less certainty as there was less precision in estimates at the lower end of the BMI distribution. Evidence for a harmful effect of reducing BMI at low BMI levels was only present in some analyses, and where present, only below 20 kg/m. A harmful effect of increasing BMI for all-cause mortality was evident above 25 kg/m, for cardiovascular mortality above 24 kg/m, for cancer mortality above 30 kg/m and for non-cardiovascular non-cancer mortality above 26 kg/m. In UK Biobank, the association between genetically predicted BMI and mortality at high BMI levels was stronger in women than in men.
CONCLUSION
This research challenges findings from previous conventional observational epidemiology and Mendelian randomisation investigations that the lowest level of mortality risk is at a BMI level of around 25 kg/m. Our results provide some evidence that reductions in BMI will increase mortality risk for a small proportion of the population, and clear evidence that increases in BMI will increase mortality risk for those with BMI above 25 kg/m.
Topics: Humans; Mendelian Randomization Analysis; Body Mass Index; United Kingdom; Female; Male; Middle Aged; Aged; Prospective Studies; Norway; Biological Specimen Banks; Neoplasms; Cardiovascular Diseases; Adult; Cause of Death; Mortality; Risk Factors; UK Biobank
PubMed: 38749693
DOI: 10.1136/bmjopen-2023-081399 -
Frontiers in Pediatrics 2024Necrotizing enterocolitis (NEC) is a life-threatening inflammatory disease. Its onset might be triggered by Toll-Like Receptor 4 (TLR4) activation via bacterial...
INTRODUCTION
Necrotizing enterocolitis (NEC) is a life-threatening inflammatory disease. Its onset might be triggered by Toll-Like Receptor 4 (TLR4) activation via bacterial lipopolysaccharide (LPS). We hypothesize that a deficiency of intestinal alkaline phosphatase (IAP), an enzyme secreted by enterocytes that dephosphorylates LPS, may contribute to NEC development.
METHODS
In this prospective pilot study, we analyzed intestinal resection specimens from surgical NEC patients, and from patients undergoing Roux-Y reconstruction for hepatobiliary disease as controls. We assessed IAP activity via enzymatic stainings and assays and explored IAP and TLR4 co-localization through immunofluorescence.
RESULTS
The study population consisted of five NEC patients (two Bell's stage IIb and three-stage IIIb, median (IQR) gestational age 25 (24-28) weeks, postmenstrual age at diagnosis 28 (26-31) weeks) and 11 controls (unknown age). There was significantly lower IAP staining in NEC resection specimens [49 (41-50) U/g of protein] compared to controls [115 (76-144), = 0.03]. LPS-dephosphorylating activity was also lower in NEC patients [0.06 (0-0.1)] than in controls [0.3 (0.2-0.5), = 0.003]. Furthermore, we observed colocalization of IAP and TLR4 in NEC resection specimens.
CONCLUSION
This study suggests a significantly lower IAP level in resection specimens of NEC patients compared to controls. This lower IAP activity suggests a potential role of IAP as a protective agent in the gut, which needs further confirmation in larger cohorts.
PubMed: 38745834
DOI: 10.3389/fped.2024.1401090