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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 -
Clinical and Translational... Apr 2022To meet the high demand for colonoscopy, the Veterans Health Administration often refers veterans to community practices. Petros et al. compared colonoscopy quality at a...
To meet the high demand for colonoscopy, the Veterans Health Administration often refers veterans to community practices. Petros et al. compared colonoscopy quality at a Veterans Affairs Medical Center with that of local community practices. Although community providers performed more timely colonoscopy than the Veterans Affairs medical center (mean 25 days earlier), colonoscopy quality was significantly lower for other important quality metrics, including adenoma detection, advanced adenoma detection, adenomas per colonoscopy, and appropriate surveillance recommendations. This study highlights the need for continued efforts to assure high-quality colonoscopy in all settings.
Topics: Adenoma; Colonoscopy; Colorectal Neoplasms; Humans; Veterans
PubMed: 35297791
DOI: 10.14309/ctg.0000000000000471 -
Gastroenterology Sep 2022Colonoscopy for colorectal cancer screening is endoscopist dependent, and colonoscopy quality improvement programs aim to improve efficacy. This study evaluated the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & AIMS
Colonoscopy for colorectal cancer screening is endoscopist dependent, and colonoscopy quality improvement programs aim to improve efficacy. This study evaluated the clinical benefit and safety of using a computer-aided detection (CADe) device in colonoscopy procedures.
METHODS
This randomized study prospectively evaluated the use of a CADe device at 5 academic and community centers by US board-certified gastroenterologists (n = 22). Participants aged ≥40 scheduled for screening or surveillance (≥3 years) colonoscopy were included; exclusion criteria included incomplete procedure, diagnostic indication, inflammatory bowel disease, and familial adenomatous polyposis. Patients were randomized by endoscopist to the standard or CADe colonoscopy arm using computer-generated, random-block method. The 2 primary endpoints were adenomas per colonoscopy (APC), the total number of adenomas resected divided by the total number of colonoscopies; and true histology rate (THR), the proportion of resections with clinically significant histology divided by the total number of polyp resections. The primary analysis used a modified intention-to-treat approach.
RESULTS
Between January and September 2021, 1440 participants were enrolled to be randomized. After exclusion of participants who did not meet the eligibility criteria, 677 in the standard arm and 682 in the CADe arm were included in a modified intention-to-treat analysis. APC increased significantly with use of the CADe device (standard vs CADe: 0.83 vs 1.05, P = .002; total number of adenomas, 562 vs 719). There was no decrease in THR with use of the CADe device (standard vs CADe: 71.7% vs 67.4%, P for noninferiority < .001; total number of non-neoplastic lesions, 284 vs 375). Adenoma detection rate was 43.9% and 47.8% in the standard and CADe arms, respectively (P = .065).
CONCLUSIONS
For experienced endoscopists performing screening and surveillance colonoscopies in the United States, the CADe device statistically improved overall adenoma detection (APC) without a concomitant increase in resection of non-neoplastic lesions (THR).
CLINICALTRIALS
gov registration: NCT04754347.
Topics: Adenoma; Colonic Polyps; Colonoscopy; Colorectal Neoplasms; Computers; Early Detection of Cancer; Humans
PubMed: 35643173
DOI: 10.1053/j.gastro.2022.05.028 -
Gut Oct 2019The effect of colonoscopy on colorectal cancer mortality is limited by several factors, among them a certain miss rate, leading to limited adenoma detection rates... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
The effect of colonoscopy on colorectal cancer mortality is limited by several factors, among them a certain miss rate, leading to limited adenoma detection rates (ADRs). We investigated the effect of an automatic polyp detection system based on deep learning on polyp detection rate and ADR.
DESIGN
In an open, non-blinded trial, consecutive patients were prospectively randomised to undergo diagnostic colonoscopy with or without assistance of a real-time automatic polyp detection system providing a simultaneous visual notice and sound alarm on polyp detection. The primary outcome was ADR.
RESULTS
Of 1058 patients included, 536 were randomised to standard colonoscopy, and 522 were randomised to colonoscopy with computer-aided diagnosis. The artificial intelligence (AI) system significantly increased ADR (29.1%vs20.3%, p<0.001) and the mean number of adenomas per patient (0.53vs0.31, p<0.001). This was due to a higher number of diminutive adenomas found (185vs102; p<0.001), while there was no statistical difference in larger adenomas (77vs58, p=0.075). In addition, the number of hyperplastic polyps was also significantly increased (114vs52, p<0.001).
CONCLUSIONS
In a low prevalent ADR population, an automatic polyp detection system during colonoscopy resulted in a significant increase in the number of diminutive adenomas detected, as well as an increase in the rate of hyperplastic polyps. The cost-benefit ratio of such effects has to be determined further.
TRIAL REGISTRATION NUMBER
ChiCTR-DDD-17012221; Results.
Topics: Adenoma; China; Colonic Polyps; Colonoscopy; Colorectal Neoplasms; Early Detection of Cancer; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Prospective Studies; Reproducibility of Results; Time Factors
PubMed: 30814121
DOI: 10.1136/gutjnl-2018-317500 -
World Journal of Gastroenterology Sep 2021The serrated pathway accounts for 30%-35% of colorectal cancer (CRC). Unlike hyperplastic polyps, both sessile serrated lesions (SSLs) and traditional serrated adenomas...
The serrated pathway accounts for 30%-35% of colorectal cancer (CRC). Unlike hyperplastic polyps, both sessile serrated lesions (SSLs) and traditional serrated adenomas are premalignant lesions, yet SSLs are considered to be the principal serrated precursor of CRCs. Serrated lesions represent a challenge in detection, classification, and removal-contributing to post-colonoscopy cancer. Therefore, it is of the utmost importance to characterize these lesions properly to ensure complete removal. A retrospective cohort study developed a diagnostic scoring system for SSLs to facilitate their detection endoscopically and subsequent removal. From the study, it can be ascertained that both indistinct border and mucus cap are essential in both recognizing and diagnosing serrated lesions. The proximal colon poses technical challenges for some endoscopists, which is why high-quality colonoscopy plays such an important role. The indistinct border of some SSLs poses another challenge due to difficult complete resection. Overall, it is imperative that gastroenterologists use the key features of mucus cap, indistinct borders, and size of at least five millimeters along with a high-quality colonoscopy and a good bowel preparation to improve the SSL detection rate.
Topics: Adenoma; Colonoscopy; Colorectal Neoplasms; Humans; Retrospective Studies
PubMed: 34629791
DOI: 10.3748/wjg.v27.i34.5625 -
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 -
Endocrine Journal Mar 2023The majority of anterior pituitary tumors behave benignly, that is, they grow slowly and do not metastasize, and were therefore called adenomas. However, they would...
The majority of anterior pituitary tumors behave benignly, that is, they grow slowly and do not metastasize, and were therefore called adenomas. However, they would frequently invade adjacent structures, leading to recurrence. One of the misleading assumptions in their previous classification was the simplistic distinction made between adenoma and carcinoma. In the upcoming WHO 2022 classification, a new terminology will be introduced: pituitary neuroendocrine tumor (PitNET) which is consistent with that used for other neuroendocrine neoplasms. In general, aggressive PitNETs are invasive and proliferative tumors with frequent recurrences, resistant to conventional treatments, and yet virtually without metastases. At present, no single morphological or histological marker has been shown as yet to reliably predict their aggressive behavior. In terms of treatment, temozolomide (TMZ) had been considered promising and the sole therapeutic option for aggressive and malignant PitNETs following failure of standard therapies. However, recent reports have disclosed that TMZ does not provide long-term control of many aggressive PitNETs. A further multidisciplinary approach is necessary for both reliable prediction and successful management of aggressive PitNETs.
Topics: Humans; Pituitary Neoplasms; Temozolomide; Adenoma; Neuroendocrine Tumors; Carcinoma
PubMed: 36858483
DOI: 10.1507/endocrj.EJ23-0007 -
Clinical Medicine (London, England) Mar 2023Pituitary incidentalomas are common findings with increasing use of modern neuroradiological imaging undertaken for symptoms unrelated to pituitary disease. The...
Pituitary incidentalomas are common findings with increasing use of modern neuroradiological imaging undertaken for symptoms unrelated to pituitary disease. The prevalence of these lesions is ∼10% in autopsy studies and the incidence varies from 10% to 38% on magnetic resonance imaging in the published literature. They are almost always benign in nature and most are non-functioning (non-secreting) adenomas. Although many individuals are asymptomatic at diagnosis, some with functioning (secreting) pituitary adenomas or larger non-functioning adenomas have symptoms. All identified cases should have a thorough clinical and endocrinological evaluation to help with precise management, which depends on the size of the lesion, hormonal status (functioning versus non-functioning adenoma) and the presence of visual deficits resulting from optic nerve compression by the pituitary adenoma. Here, we provide an overview of the initial assessment and management of pituitary incidentalomas for clinicians not routinely involved in the management of pituitary disease.
Topics: Humans; Incidental Findings; Pituitary Neoplasms; Pituitary Diseases; Adenoma; Magnetic Resonance Imaging
PubMed: 36958836
DOI: 10.7861/clinmed.2023-0020 -
Endocrinology and Metabolism (Seoul,... Jun 2020Pituitary adenomas (PAs) are defined as benign monoclonal tumors in the pituitary gland that cause symptoms due to either hormonal hypersecretion or a space-occupying... (Review)
Review
Pituitary adenomas (PAs) are defined as benign monoclonal tumors in the pituitary gland that cause symptoms due to either hormonal hypersecretion or a space-occupying effect, and are classified as functioning or non-functioning. Because of their rarity and slow-growing with symptomless nature in most cases, it has been challenging to investigate the epidemiology of PAs. Considering their public health impact and association with increased morbidity and mortality, however, it is essential to understand the prevalence and incidence of PAs in order to improve patient outcomes and to minimize the resultant burden on the health care system. Fortunately, developments in imaging modalities and easier access to large-scale population data have enabled investigators to analyze the epidemiology of PAs more accurately. This review summarizes previously reported epidemiologic data on functioning PAs in Korea and other countries.
Topics: Adenoma; Humans; Incidence; Pituitary Neoplasms; Public Health
PubMed: 32615708
DOI: 10.3803/EnM.2020.35.2.237 -
International Journal of Molecular... Jun 2022Cushing's disease represents 60-70% of all cases of Cushing's syndrome, presenting with a constellation of clinical features associated with sustained hypercortisolism.... (Review)
Review
Cushing's disease represents 60-70% of all cases of Cushing's syndrome, presenting with a constellation of clinical features associated with sustained hypercortisolism. Molecular alterations in corticotrope cells lead to the formation of ACTH-secreting adenomas, with subsequent excessive production of endogenous glucocorticoids. In the last few years, many authors have contributed to analyzing the etiopathogenesis and pathophysiology of corticotrope adenomas, which still need to be fully clarified. New molecular modifications such as somatic mutations of and other genes have been identified, and several case series and case reports have been published, highlighting new molecular alterations that need to be explored. To investigate the current knowledge of the genetics of ACTH-secreting adenomas, we performed a bibliographic search of the recent scientific literature to identify all pertinent articles. This review presents the most recent updates on somatic and germline mutations underlying Cushing's disease. The prognostic implications of these mutations, in terms of clinical outcomes and therapeutic scenarios, are still debated. Further research is needed to define the clinical features associated with the different genotypes and potential pharmacological targets.
Topics: ACTH-Secreting Pituitary Adenoma; Adenoma; Adrenocorticotropic Hormone; Cushing Syndrome; Humans; Pituitary ACTH Hypersecretion
PubMed: 35743266
DOI: 10.3390/ijms23126824