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JAMA Nov 2023Noninvasive tests for colorectal cancer screening must include sensitive detection of colorectal cancer and precancerous lesions. These tests must be validated for the... (Comparative Study)
Comparative Study
IMPORTANCE
Noninvasive tests for colorectal cancer screening must include sensitive detection of colorectal cancer and precancerous lesions. These tests must be validated for the intended-use population, which includes average-risk individuals 45 years or older.
OBJECTIVE
To evaluate the sensitivity and specificity of a noninvasive, multitarget stool RNA (mt-sRNA) test (ColoSense) test compared with results from a colonoscopy.
DESIGN, SETTING, AND PARTICIPANTS
This phase 3 clinical trial (CRC-PREVENT) was a blinded, prospective, cross-sectional study to support a premarket approval application for a class III medical device. A total of 8920 participants were identified online using social media platforms and enrolled from June 2021 to June 2022 using a decentralized nurse call center. All participants completed the mt-sRNA test, which incorporated a commercially available fecal immunochemical test (FIT), concentration of 8 RNA transcripts, and participant-reported smoking status. Stool samples were collected prior to participants completing a colonoscopy at their local endoscopy center. The mt-sRNA test results (positive or negative) were compared with index lesions observed on colonoscopy. Over the course of 12 months, individuals 45 years and older were enrolled in the clinical trial using the decentralized recruitment strategy. Participants were enrolled from 49 US states and obtained colonoscopies at more than 3800 different endoscopy centers.
MAIN OUTCOMES AND MEASURES
The primary outcomes included the sensitivity of the mt-sRNA test for detecting colorectal cancer and advanced adenomas and the specificity for no lesions on colonoscopy.
RESULTS
The mean (range) age of participants was 55 (45-90) years, with 4% self-identified as Asian, 11% as Black, and 7% as Hispanic. Of the 8920 eligible participants, 36 (0.40%) had colorectal cancer and 606 (6.8%) had advanced adenomas. The mt-sRNA test sensitivity for detecting colorectal cancer was 94%, sensitivity for detecting advanced adenomas was 46%, and specificity for no lesions on colonoscopy was 88%. The mt-sRNA test showed significant improvement in sensitivity for colorectal cancer (94% vs 78%; McNemar P = .01) and advanced adenomas (46% vs 29%; McNemar P < .001) compared with results of the FIT.
CONCLUSIONS AND RELEVANCE
In individuals 45 years and older, the mt-sRNA test showed high sensitivity for colorectal neoplasia (colorectal cancer and advanced adenoma) with significant improvement in sensitivity relative to the FIT. Specificity for no lesions on colonoscopy was comparable to existing molecular diagnostic tests.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04739722.
Topics: Aged; Aged, 80 and over; Humans; Middle Aged; Adenoma; Colonoscopy; Colorectal Neoplasms; Cross-Sectional Studies; Early Detection of Cancer; Feces; Mass Screening; Occult Blood; Prospective Studies; RNA, Small Untranslated; RNA; Immunochemistry
PubMed: 37870871
DOI: 10.1001/jama.2023.22231 -
Nature Reviews. Endocrinology Oct 2023Cushing disease caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary corticotroph adenoma leads to hypercortisolaemia with high mortality due to... (Review)
Review
Cushing disease caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary corticotroph adenoma leads to hypercortisolaemia with high mortality due to metabolic, cardiovascular, immunological, neurocognitive, haematological and infectious conditions. The disorder is challenging to diagnose because of its common and heterogenous presenting features and the biochemical pitfalls of testing levels of hormones in the hypothalamic-pituitary-adrenal axis. Several late-night salivary cortisol and 24-h urinary free cortisol tests are usually required as well as serum levels of cortisol after a dexamethasone suppression test. MRI might only identify an adenoma in 60-75% of patients and many adenomas are small. Therefore, inferior petrosal sinus sampling remains the gold standard for confirmation of ACTH secretion from a pituitary source. Initial treatment is usually transsphenoidal adenoma resection, but preoperative medical therapy is increasingly being used in some countries and regions. Other management approaches are required if Cushing disease persists or recurs following surgery, including medications to modulate ACTH or block cortisol secretion or actions, pituitary radiation, and/or bilateral adrenalectomy. All patients require lifelong surveillance for persistent comorbidities, clinical and biochemical recurrence, and treatment-related adverse effects (including development of treatment-associated hypopituitarism). In this Review, we discuss challenges in the management of Cushing disease in adults and provide information to guide clinicians when planning an integrated and individualized approach for each patient.
Topics: Adult; Humans; Pituitary ACTH Hypersecretion; Hydrocortisone; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; ACTH-Secreting Pituitary Adenoma; Adenoma; Adrenocorticotropic Hormone; Pituitary Neoplasms
PubMed: 37537306
DOI: 10.1038/s41574-023-00868-7 -
Acta Gastro-enterologica Belgica 2023Biliary papillomatosis (BP) is a rare disorder of the biliary tract characterized by the presence of multiple papillary adenomas spread along the biliary tree. Although...
Biliary papillomatosis (BP) is a rare disorder of the biliary tract characterized by the presence of multiple papillary adenomas spread along the biliary tree. Although benign, it carries a significant risk of malignant transformation. Due to low sensitivity and specificity of conventional radiologic modalities, the diagnosis as well as estimation of disease extent is difficult. Endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreaticography (ERCP) are superior although direct peroral cholangioscopy (POC) is currently the most accurate diagnostic method. Mainly because it provides more detailed information and makes targeted histological diagnosis possible. The treatment of biliary papillomatosis consists of surgical resection, liver transplantation (LT) or a combination of both. Unfortunately, the recurrence rate after radical surgery without LT remains high due to the diffuse distribution of the disease.
Topics: Humans; Cholangiopancreatography, Endoscopic Retrograde; Bile Duct Neoplasms; Sensitivity and Specificity; Adenoma; Papilloma
PubMed: 37814564
DOI: 10.51821/86.3.11733 -
Best Practice & Research. Clinical... Oct 2023Post-polypectomy surveillance has proven to reduce colorectal cancer (CRC) incidence in patients with high-risk polyps, but it implies a major burden on colonoscopy... (Review)
Review
Post-polypectomy surveillance has proven to reduce colorectal cancer (CRC) incidence in patients with high-risk polyps, but it implies a major burden on colonoscopy units. Therefore, it should be targeted to individuals with a higher risk. Different societies have published guidelines on surveillance after resection of polyps, with notable discrepancies among them, and many recommendations come from low-quality evidence based on surrogate measures, such as risk of advanced adenoma, and not CRC risk. In this review, we aimed to summarize the evidence supporting post-polypectomy surveillance, compare the recently updated major guidelines, and discuss the existing discrepancies on this topic. Briefly, patients with adenomas ≥10 mm or high-grade dysplasia and patients with serrated polyps ≥10 mm or dysplasia are generally considered to have an increased risk of metachronous CRC and require surveillance, whereas the indication of surveillance is not clearly established in patients without these high-risk features.
Topics: Humans; Colonic Polyps; Colorectal Neoplasms; Colonoscopy; Risk Factors; Adenoma
PubMed: 37852710
DOI: 10.1016/j.bpg.2023.101848 -
Nature Reviews. Nephrology Dec 2023Primary aldosteronism is the most common single cause of hypertension and is potentially curable when only one adrenal gland is the culprit. The importance of primary... (Review)
Review
Primary aldosteronism is the most common single cause of hypertension and is potentially curable when only one adrenal gland is the culprit. The importance of primary aldosteronism to public health derives from its high prevalence but huge under-diagnosis (estimated to be <1% of all affected individuals), despite the consequences of poor blood pressure control by conventional therapy and enhanced cardiovascular risk. This state of affairs is attributable to the fact that the tools used for diagnosis or treatment are still those that originated in the 1970-1990s. Conversely, molecular discoveries have transformed our understanding of adrenal physiology and pathology. Many molecules and processes associated with constant adrenocortical renewal and interzonal metamorphosis also feature in aldosterone-producing adenomas and aldosterone-producing micronodules. The adrenal gland has one of the most significant rates of non-silent somatic mutations, with frequent selection of those driving autonomous aldosterone production, and distinct clinical presentations and outcomes for most genotypes. The disappearance of aldosterone synthesis and cells from most of the adult human zona glomerulosa is the likely driver of the mutational success that causes aldosterone-producing adenomas, but insights into the pathways that lead to constitutive aldosterone production and cell survival may open up opportunities for novel therapies.
Topics: Adult; Humans; Aldosterone; Hyperaldosteronism; Public Health; Molecular Medicine; Adenoma
PubMed: 37612380
DOI: 10.1038/s41581-023-00753-6 -
Endocrinology and Metabolism Clinics of... Dec 2023Pituitary adenomas have been increasingly detected in recent years, especially in the older population. Black patients have a higher incidence than other racial groups.... (Review)
Review
Pituitary adenomas have been increasingly detected in recent years, especially in the older population. Black patients have a higher incidence than other racial groups. In patients with functioning tumors, presentation and comorbidities are influenced by age and sex, whereas the impact of ethnoracial background is unclear. Active surveillance recommendation and surgery refusal disproportionally affect Black and older patients. The likelihood of surgery at high-volume centers is lower for patients of Black or Hispanic background, uninsured or with lower socioeconomic status. Multicentric studies are necessary to delineate the influence of sociodemographic factors according to the adenoma type and to address the causes of health care disparities.
Topics: Humans; Adenoma; Hispanic or Latino; Pituitary Neoplasms; Sociodemographic Factors; Black or African American; Medically Uninsured; Low Socioeconomic Status
PubMed: 37865483
DOI: 10.1016/j.ecl.2023.05.008 -
Gastroenterology Clinics of North... Mar 2024Colorectal polyps are common, and their diagnosis and classification represent a major component of gastrointestinal pathology practice. The majority of colorectal... (Review)
Review
Colorectal polyps are common, and their diagnosis and classification represent a major component of gastrointestinal pathology practice. The majority of colorectal polyps represent precursors of either the chromosomal instability or serrated neoplasia pathways to colorectal carcinoma. Accurate reporting of these polyps has major implications for surveillance and thus for cancer prevention. In this review, we discuss the key histologic features of the major colorectal polyps with a particular emphasis on diagnostic pitfalls and areas of contention.
Topics: Humans; Colonic Polyps; Adenoma; Colorectal Neoplasms
PubMed: 38280746
DOI: 10.1016/j.gtc.2023.10.002 -
Gastroenterology Sep 2023Fecal tests currently used for colorectal cancer (CRC) screening show limited accuracy in detecting early tumors or precancerous lesions. In this respect, we...
BACKGROUND & AIMS
Fecal tests currently used for colorectal cancer (CRC) screening show limited accuracy in detecting early tumors or precancerous lesions. In this respect, we comprehensively evaluated stool microRNA (miRNA) profiles as biomarkers for noninvasive CRC diagnosis.
METHODS
A total of 1273 small RNA sequencing experiments were performed in multiple biospecimens. In a cross-sectional study, miRNA profiles were investigated in fecal samples from an Italian and a Czech cohort (155 CRCs, 87 adenomas, 96 other intestinal diseases, 141 colonoscopy-negative controls). A predictive miRNA signature for cancer detection was defined by a machine learning strategy and tested in additional fecal samples from 141 CRC patients and 80 healthy volunteers. miRNA profiles were compared with those of 132 tumors/adenomas paired with adjacent mucosa, 210 plasma extracellular vesicle samples, and 185 fecal immunochemical test leftover samples.
RESULTS
Twenty-five miRNAs showed altered levels in the stool of CRC patients in both cohorts (adjusted P < .05). A 5-miRNA signature, including miR-149-3p, miR-607-5p, miR-1246, miR-4488, and miR-6777-5p, distinguished patients from control individuals (area under the curve [AUC], 0.86; 95% confidence interval [CI], 0.79-0.94) and was validated in an independent cohort (AUC, 0.96; 95% CI, 0.92-1.00). The signature classified control individuals from patients with low-/high-stage tumors and advanced adenomas (AUC, 0.82; 95% CI, 0.71-0.97). Tissue miRNA profiles mirrored those of stool samples, and fecal profiles of different gastrointestinal diseases highlighted miRNAs specifically dysregulated in CRC. miRNA profiles in fecal immunochemical test leftover samples showed good correlation with those of stool collected in preservative buffer, and their alterations could be detected in adenoma or CRC patients.
CONCLUSIONS
Our comprehensive fecal miRNome analysis identified a signature accurately discriminating cancer aimed at improving noninvasive diagnosis and screening strategies.
Topics: Humans; MicroRNAs; Cross-Sectional Studies; Biomarkers, Tumor; Colorectal Neoplasms; Sequence Analysis, RNA; Adenoma
PubMed: 37263306
DOI: 10.1053/j.gastro.2023.05.037 -
Seminars in Nuclear Medicine Jul 2023Tumors of the pituitary gland, although mostly benign adenomas, are a cause of significant morbidity and even excess mortality due to local compressive effects (eg... (Review)
Review
Tumors of the pituitary gland, although mostly benign adenomas, are a cause of significant morbidity and even excess mortality due to local compressive effects (eg visual loss, hypopituitarism) and unregulated hormone secretion (eg acromegaly or Cushing Disease). Surgery, radiotherapy, and medical management (sometimes in combination) may be needed to mitigate the effects of tumor expansion and endocrine dysfunction. Magnetic resonance imaging (MRI) plays a central role in treatment planning for most patients. However, it does not always reliably identify the site(s) of primary or recurrent disease, especially where post-treatment remodeling results in indeterminate anatomical appearances. In these contexts, molecular imaging is a potential game-changer, allowing precise localization of sites of active disease and enabling safe and effective targeted intervention when patients would otherwise be consigned to expensive life-long medication. For pituitary and parasellar imaging, PET is the preferred modality due to its superior spatial resolution and sensitivity compared with SPECT, and an array of PET radioligands have been studied in different pituitary adenoma (PA) subtypes. While F-fluorodeoxyglucose (F-FDG) is widely available, significant heterogeneity in tumoral uptake has limited its use. Instead, ligands targeting specific molecular pathways relevant to PA biology (eg somatostatin or dopamine receptor expression, amino acid uptake) are increasingly preferred and are beginning to find application in routine clinical practice. In addition, novel approaches to distinguish adenomatous tissue from normal gland (eg through comparison of images obtained with different radiotracers) and increase confidence that a suspected abnormal focus is indeed pathological (eg through subtraction imaging) have been proposed. It is likely therefore that molecular imaging will continue to find increasing application in the management of pituitary tumors just as it already does in other endocrine disorders.
Topics: Humans; Pituitary Neoplasms; Adenoma; Fluorodeoxyglucose F18; Positron-Emission Tomography; Magnetic Resonance Imaging; Molecular Imaging
PubMed: 36966020
DOI: 10.1053/j.semnuclmed.2023.02.005 -
Archives of Medical Research Dec 2023Pituitary adenomas (PA), comprising 10-20% of intracranial tumors, are classified as functioning and non-functioning and are further divided by size. Non-functioning... (Review)
Review
BACKGROUND
Pituitary adenomas (PA), comprising 10-20% of intracranial tumors, are classified as functioning and non-functioning and are further divided by size. Non-functioning tumors cause mechanical symptoms while functioning ones result in hormonal hypersecretion syndromes. Initial treatment involves surgery, with medical treatment for prolactinomas. Radiotherapy (RT) is employed as an adjuvant treatment, with various modalities including conventional, stereotactic radiosurgery (SRS), and fractionated stereotactic RT (FSRT). Although effective, RT is associated with complications and toxicities such as hypopituitarism, optic neuritis, secondary CNS tumors, and neurocognitive deficits.
AIM
Describe the information on mortality from radiotherapy as treatment of functioning PA.
METHODS
A PubMed search spanning 2000-2017 was conducted for articles on pituitary RT.
RESULTS
Conventional RT entails high-energy radiation over multiple sessions, while SRS delivers precise high doses in a single session. FSRT offers enhanced precision using a linear accelerator, delivering multiple doses. Optic structure proximity and tumor volume dictate RT modality. Studies have shown SRS and FSRT's efficacy in tumor and endocrine control, with variable risks and complications. Mortality rates in pituitary adenomas treated with RT have been evaluated, revealing complexities. Acromegaly, associated with increased mortality due to cerebrovascular disease, may result from RT. Irradiation of non-functioning pituitary macroadenomas also elevates cerebrovascular risk, while radiotherapy-induced hypopituitarism is associated with increased cardiovascular mortality. RT-induced damage is attributed to microvascular lesions and arteriolar changes.
CONCLUSION
Modern techniques mitigate complications, and although safer, long-term studies are needed. Multidisciplinary evaluation guides the treatment decision, optimizing efficacy and minimizing risk, ultimately improving the patient's quality of life.
Topics: Humans; Pituitary Neoplasms; Quality of Life; Adenoma; Radiosurgery; Hypopituitarism; Treatment Outcome
PubMed: 37940504
DOI: 10.1016/j.arcmed.2023.102900