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BMC Endocrine Disorders Jun 2024Activating mutation in Ubiquitin-specific peptidase (USP8) is identified to enhance cell proliferation and adrenocorticotropic hormone (ACTH) secretion from corticotroph...
OBJECTIVE
Activating mutation in Ubiquitin-specific peptidase (USP8) is identified to enhance cell proliferation and adrenocorticotropic hormone (ACTH) secretion from corticotroph pituitary adenoma. We investigated the USP8 variant status in a population of Iranian people with functional corticotroph pituitary adenoma (FCPA). Moreover, a systematic review was conducted to thoroughly explore the role of USP8 variants and the related pathways in corticotroph adenomas, genotype-phenotype correlation in USP8-mutated individuals with FCPA, and the potential role of USP8 and epidermal growth factor receptor (EGFR) as targeted therapies in PFCAs.
METHODS
Genetic analysis of 20 tissue samples from 19 patients with PFCAs was performed using Sanger sequencing. Moreover, a systematic literature review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Scopus, web of Sciences, and Cochrane databases were searched. The last search was performed on 20 September 2023 for all databases.
RESULTS
In our series, we found two somatic mutations including a 7-bp deletion variant: c.2151_2157delCTCCTCC, p. Ser718GlnfsTer3, and a missense variant: c.2159 C > G, p. Pro720Arg (rs672601311) in exon 14. The Systematic review indicated USP8 variant in 35% of corticotroph adenomas, with the highest frequency (25%) in 720 code regions, p. Pro720Arg. Data regarding the impact of USP8 mutational status on clinical characteristics and outcomes in FCPAs are inconsistent. Moreover, Pasireotide as well as inhibitors of EGFR such as Gefitinib and Lapatinib, as well as USP8 inhibitors including -ehtyloxyimino9H-indeno (1, 2-b) pyrazine-2, 3-dicarbonitrile, DUBs-IN-2, and RA-9 indicated promising results in treatment of corticotroph adenomas.
CONCLUSION
Although the USP8-EGFR system has been identified as the main trigger and target of corticotroph tumorigenesis, more precise multicenter studies are required to yield more consistent information regarding the phenotype-genotype correlation and to develop effective targeted therapies.
Topics: Humans; Ubiquitin Thiolesterase; Iran; Endosomal Sorting Complexes Required for Transport; Pituitary ACTH Hypersecretion; Adult; Female; Male; Endopeptidases; Mutation; Middle Aged; ACTH-Secreting Pituitary Adenoma; Middle Eastern People
PubMed: 38862897
DOI: 10.1186/s12902-024-01619-z -
Journal of the ASEAN Federation of... 2024Insulinoma is one of the causes of recurrent hypoglycemia, one of the chief complaints for emergency department admission. The gold standard in diagnosing insulinoma is... (Review)
Review
BACKGROUND
Insulinoma is one of the causes of recurrent hypoglycemia, one of the chief complaints for emergency department admission. The gold standard in diagnosing insulinoma is a 72-hour fasting test which is inconvenient and inefficient as it requires hospitalization. Research has found that measurement of insulin and C-peptide during OGTT may help diagnose insulinoma. We aimed to assess the diagnostic value of OGTT in diagnosing insulinoma.
METHODOLOGY
The literature search was conducted on 19 August 2022 using several databases (MEDLINE, Scopus, Embase, and ScienceDirect). All studies that measured OGTT as diagnostic tools in diagnosing insulinoma and 72-hour fasting test as reference standard were included. The quality assessment of the selected studies was based on the Centre of Evidence-Based Medicine University of Oxford and the Quality Assessment of Diagnostic Accuracy-2 tool (QUADAS-2). Analysis of the included studies was performed qualitatively. This study was registered on PROSPERO (CRD42022360205).
RESULTS
A total of two case-control studies (106 patients) were included, which were at risk of bias and low concern of applicability. Both studies demonstrated that the combination of insulin and C-peptide levels measured during OGTT had high specificity, sensitivity, positive predictive value, and negative predictive value in diagnosing insulinoma compared to the reference standard. A logistic regression model of 8.305 - (0.441 × insulin 2-h/0-h) - (1.679 × C-peptide 1-h/0-h) >0.351 has the highest diagnostic value in one study (AUC 0.97, Sensitivity 86.5%, Specificity 95.2%, PPV 94.1, NPV 88.9).
CONCLUSION
The measurement of 0-h and 2-h insulin and C-peptide levels during 2-h OGTT was found in two small case-control studies with a total of 106 patients to have good sensitivity and specificity. However, due to these limitations, future research is still needed to validate the potential use of OGTT for the diagnosis of insulinoma.
Topics: Humans; C-Peptide; Insulinoma; Glucose Tolerance Test; Pancreatic Neoplasms; Insulin; Sensitivity and Specificity; Insulin Secretion
PubMed: 38863915
DOI: 10.15605/jafes.039.01.16 -
Frontiers in Endocrinology 2024Acromegaly is a rare endocrine disorder caused by hypersecretion of growth hormone (GH) from a pituitary adenoma. Elevated GH levels stimulate excess production of...
UNLABELLED
Acromegaly is a rare endocrine disorder caused by hypersecretion of growth hormone (GH) from a pituitary adenoma. Elevated GH levels stimulate excess production of insulin-like growth factor 1 (IGF-1) which leads to the insidious onset of clinical manifestations. The most common primary central nervous system (CNS) tumors, meningiomas originate from the arachnoid layer of the meninges and are typically benign and slow-growing. Meningiomas are over twice as common in women as in men, with age-adjusted incidence (per 100,000 individuals) of 10.66 and 4.75, respectively. Several reports describe co-occurrence of meningiomas and acromegaly. We aimed to determine whether patients with acromegaly are at elevated risk for meningioma. Investigation of the literature showed that co-occurrence of a pituitary adenoma and a meningioma is a rare phenomenon, and the majority of cases involve GH-secreting adenomas. To the best of our knowledge, a systematic review examining the association between meningiomas and elevated GH levels (due to GH-secreting adenomas in acromegaly or exposure to exogenous GH) has never been conducted. The nature of the observed coexistence between acromegaly and meningioma -whether it reflects causation or mere co-association -is unclear, as is the pathophysiologic etiology.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42022376998.
Topics: Humans; Meningioma; Acromegaly; Meningeal Neoplasms; Human Growth Hormone; Risk Factors; Adenoma
PubMed: 38919490
DOI: 10.3389/fendo.2024.1407615 -
Open Forum Infectious Diseases Nov 2023Invasive infection with complex (SBSEC) bacteria is associated with underlying colorectal neoplasia. However, the link between intestinal or fecal colonization with...
BACKGROUND
Invasive infection with complex (SBSEC) bacteria is associated with underlying colorectal neoplasia. However, the link between intestinal or fecal colonization with SBSEC isolates or antibody responses to SBSEC members and colorectal cancer is not thoroughly investigated in the literature.
METHODS
We searched the PubMed, EMBASE, and Web of Science databases for case-control studies as well as retrospective or prospective cohort studies reporting an association between SBSEC bacteria and colorectal neoplasia.
RESULTS
We identified 22 studies (15 case-control and 7 cohort) that met our inclusion criteria. Among the cohort studies, patients with SBSEC bacteremia were 3.73 times more likely to have underlying colorectal cancer compared with individuals with no bacteremia (relative risk [RR], 3.73; 95% CI, 2.79-5.01), whereas the risk of underlying colorectal adenoma in patients with SBSEC bacteremia was not significantly increased (RR, 5.00; 95% CI, 0.83-30.03). In case-control studies, patients with colorectal cancer were 2.27 times more likely to have evidence of intestinal or fecal colonization with SBSEC isolates (odds ratio [OR], 2.27; 95% CI, 1.11-4.62) and immunoglobulin G (IgG) antibody responses to SBSEC antigens (OR, 2.27; 95% CI, 1.06-4.86) compared with controls. Patients with colorectal adenoma were not more likely to be colonized with SBSEC isolates compared with controls (OR, 1.12; 95% CI, 0.55-2.25).
CONCLUSIONS
Apart from the well-established association of SBSEC bacteremia and underlying colorectal cancer, intestinal or fecal colonization with SBSEC isolates and IgG antibody responses to SBSEC antigens were higher in patients with colorectal cancer compared with controls. Neither bacteremia from SBSEC isolates nor colonization with SBSEC bacteria was associated with underlying colorectal adenoma.
PubMed: 38023558
DOI: 10.1093/ofid/ofad547 -
Annals of Gastroenterology 2023Add-on devices with projections, e.g., Endocuff, Endocuff Vision, EndoRings, and Wingcap, placed on the distal tip of the colonoscope promise to improve the detection of...
BACKGROUND
Add-on devices with projections, e.g., Endocuff, Endocuff Vision, EndoRings, and Wingcap, placed on the distal tip of the colonoscope promise to improve the detection of precancerous lesions. We performed a meta-analysis to evaluate the performance of these devices exclusively among individuals undergoing colonoscopy for screening purpose.
METHODS
A computerized literature search was performed across MEDLINE and Cochrane Library databases for randomized controlled trials that compared standard colonoscopy (SC) to procedures using add-on devices. The primary outcome was adenoma detection rate (ADR), while secondary outcomes included polyp detection rate (PDR), advanced ADR (AADR), and sessile serrated lesion detection rate (SSLDR). The effect size on study outcomes was calculated using a random-effects model and presented as the risk ratio (RR) and 95% confidence interval (CI).
RESULTS
Seven studies enrolling a total of 5785 patients were included. The use of add-on-devices with projections was associated with a higher ADR compared to SC: 45.9% vs. 41.1%; RR 1.18, 95%CI 1.02-1.37; P=0.03; =79%. Although PDR was higher in screening colonoscopies assisted by add-on devices as compared to SC, the difference failed to reach significance: 55.1% vs. 50.8%; RR 1.10, 95%CI 0.96-1.26; P=0.17; =75%. No difference was found between procedures assisted by add-on devices with projections and SC colonoscopies in terms of AADR (18.5% vs. 17.6%; RR 1.00, 95%CI 0.79-1.27; P=0.98; =56%) or SSLDR (6.8% vs. 5.8%; RR 1.17, 95%CI 0.95-1.44; P=0.15; =0%).
CONCLUSION
Colonoscopy assisted by add-on devices with projections achieves a better ADR compared to SC among individuals undergoing screening for bowel cancer.
PubMed: 37664236
DOI: 10.20524/aog.2023.0820 -
Gland Surgery Jan 2024Primary hyperparathyroidism (pHPT) is an endocrine disorder typically characterized by elevated serum calcium and elevated parathyroid hormone (PTH). While... (Review)
Review
BACKGROUND
Primary hyperparathyroidism (pHPT) is an endocrine disorder typically characterized by elevated serum calcium and elevated parathyroid hormone (PTH). While parathyroidectomy is the standard treatment, non-operative intervention such as radiofrequency ablation (RFA) has been adopted as an alternative for the management of pHPT, as it has been utilized in other endocrine glands such as thyroid and adrenal. In this literature review, we aim to evaluate the current practice of RFA for pHPT.
METHODS
A systematic literature search using PubMed, Web of Science, and Embase through June 2022 was conducted. Studies included in the review consisted of patient cohorts who had an unequivocal diagnosis of pHPT and underwent the treatment of pHPT with RFA. When more than one study was published from a similar cohort of patients, only the study with the most number of patients was considered. Studies included were assessed for bias using the critical appraisal instruments from the Joanna Briggs Institute (JBI) System.
RESULTS
A total of 14 studies describing 167 parathyroid glands treated in 163 patients were reviewed. The overall cure rate was 91.2%, with 5 patients undergoing more than one ablation. The most common adverse effect encountered was temporary dysphonia. Incomplete ablation and missed multiglandular disease were the most common reasons for RFA treatment failure.
CONCLUSIONS
RFA may be an effective and safe alternative to parathyroidectomy in select patients with a well-localized, well-located parathyroid adenoma. Additional long-term data are needed to refine its role in the pHPT treatment algorithm.
PubMed: 38323227
DOI: 10.21037/gs-22-546 -
Endoscopy International Open Apr 2024Published studies report a higher adenoma detection rate (ADR) for FIT-DNA as compared with FIT. Data are less replete about the performance of stool-based tests for... (Review)
Review
Published studies report a higher adenoma detection rate (ADR) for FIT-DNA as compared with FIT. Data are less replete about the performance of stool-based tests for sessile serrated polyp (SSP) detection. We performed a meta-analysis to evaluate the performance of FIT and FIT-DNA testing for SSP detection rate (SSPDR) in patients undergoing colonoscopy for follow up of positive noninvasive tests. A comprehensive literature search of multiple databases (until September 2022) was performed to identify studies reporting SSPDR in patients with positive FIT or FIT-DNA tests. The outcome was overall colonoscopy detection of any SSPs and advanced serrated polyps (ASP: SSP ≥ 10 mm and/or dysplasia). Included were 482,405 patients (52.4% females) with a mean age of 62.3 ± 4.4 years from 23 studies. The pooled SSPDR for all positive stool-based tests was 5.3% and higher for FIT-DNA (15.0%, 95% confidence interval [CI] 8.3-25.7) versus FIT (4.1%, 95% CI 3.0-5.6; = 0.0002). The overall pooled ASP detection rate was 1.4% (95% CI 0.81-2.3) and higher for FIT-DNA (3.8 %, 95% CI 1.7-8.6) compared with FIT (0.71%, 95% CI 0.36-1.4; <0.01). SSPDR with FIT-DNA was also significantly higher than FIT when the FIT cutoff was >10 ug/g and in FIT-positive patients in studies conducted in North America ( <0.05). FIT-DNA outperformed FIT in both SSP and ASP detection including FIT with a lower threshold cutoff of >10 ug/g. Further comparative studies are needed to assess the impact of our findings on colorectal cancer reduction.
PubMed: 38585019
DOI: 10.1055/a-2256-3411 -
Gastrointestinal Endoscopy Jun 2024Serrated polyps (SPs) are precursors to 15-20% of colorectal cancers (CRCs). However, there are uncertainties regarding which SPs require surveillance and at what... (Review)
Review
BACKGROUND AND AIMS
Serrated polyps (SPs) are precursors to 15-20% of colorectal cancers (CRCs). However, there are uncertainties regarding which SPs require surveillance and at what intervals, with recommendations adapted from those for adenomas in the absence of solid evidence. Our aim was to assess which SP risk characteristics relate to a higher risk of metachronous CRC or advanced polyps.
METHODS
We systematically searched PubMed, EMBASE, and Cochrane for cohort, case-control studies, and clinical trials from inception to Dec 31, 2023, for CRC or advanced polyps [advanced adenoma (AA) or advanced SP] incidence at surveillance stratified by baseline SP size, dysplasia, location, and multiplicity. We defined advanced SPs as those >10mm or with dysplasia. CRC and advanced polyp incidence per 1,000 person-years (p-y) were estimated. We performed a meta-analysis by calculating pooled relative risks (RR) using a random-effects model.
RESULTS
5,903 studies were reviewed and 14 included, with 493,949 patients (mean age 59·5 years, 55% men). Mean follow-up was 4·9 years. CRC incidence per 1,000 p-y was 2·09 (95%CI 1·29-2·90) for advanced SP, 1·52 (0·78-2·25) for SP>10mm, 5·86 (2·16-9·56) for SP with dysplasia, 1·18 (0·77-1·60) for proximal SP, 0·52 (0·08-1·12) for >3SP, 0·50 (0·35-0·66) for non-advanced SP, and 0·44 (0·41-0·46) for normal colonoscopy. Metachronous CRC risk was higher in advanced SP vs non-advanced SP (RR 1·84, 95%CI 1·11-3·04), and vs normal colonoscopy (RR 2·92, 2·26-3·77); in SP>10mm vs <10mm (RR 2·61, 1·43-4·77), and vs normal colonoscopy (RR 3·52, 2·17-5·69); and in SP with dysplasia vs normal colonoscopy (RR 2·71, 2·00-3·67). No increase in CRC or advanced polyp risk was found in patients with proximal vs distal SP, nor in >3SP vs 1-2SP.
CONCLUSIONS
CRC risk is significantly higher in patients with baseline advanced SP after 4·9 years of follow-up, with risk magnitudes similar to those described for AA, supporting the current recommendation for 3-year surveillance in patients with advanced SP.
PubMed: 38851458
DOI: 10.1016/j.gie.2024.05.021 -
Frontiers in Endocrinology 2024Most pancreatic insulinomas can be treated by minimally invasive modalities. The aim of this meta-analysis was to assess the clinical outcomes of endoscopic ultrasound... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Most pancreatic insulinomas can be treated by minimally invasive modalities. The aim of this meta-analysis was to assess the clinical outcomes of endoscopic ultrasound (EUS)-guided ablation and minimally invasive surgery (MIS) in the treatment of pancreatic insulinoma.
MATERIALS AND METHODS
Online databases were searched for relevant studies. The primary aim was to compare the rates of adverse events (AEs) and the secondary aims were to compare the clinical and technical success rates, length of hospital stays, and symptom recurrence rates between EUS and MIS approaches.
RESULTS
Eight studies with 150 patients were identified that reported EUS-guided ablation outcomes, forming the EUS group, and 9 studies with 236 patients reported MIS outcomes, forming the MIS group. The pooled median age of the included patients in the EUS group was greater than that of the MIS group (64.06 vs. 44.98 years old, < 0.001). Also, the technical success rate was significantly higher in the EUS group (100% vs. 96.6%, 0.025), while the clinical success was significantly higher (6%) in the MIS group (94% vs. 98.7%, 0.021). The AE rates (18.7% vs. 31.1%, 0.012) and severe AE rates (1.3% vs. 7.9%, 0.011) were significantly lower in the EUS group. The median length of hospital stay in the EUS group (2.68 days, 95% CI: 1.88-3.48, I60.3%) was significantly shorter than in the MIS group (7.40 days, 95% CI: 6.22-8.58, I42.2%, < 0.001). The recurrence rate was significantly higher in the EUS group (15.3% vs. 1.3%, < 0.001).
CONCLUSIONS
EUS-guided ablation is associated with a lower AE rate and a shorter length of hospital stay, but a higher recurrence rate for the treatment of insulinoma compared with MIS. The EUS approach may be an alternative, even first-line, treatment for poor surgery candidates.
Topics: Humans; Insulinoma; Pancreatic Neoplasms; Minimally Invasive Surgical Procedures; Endosonography; Treatment Outcome; Length of Stay
PubMed: 38645424
DOI: 10.3389/fendo.2024.1367068 -
Frontiers in Oncology 2023To evaluate the efficacy of Difluoromethylornithine (DFMO) chemoprevention in the high-risk population for colorectal cancer (CRC).
OBJECTIVES
To evaluate the efficacy of Difluoromethylornithine (DFMO) chemoprevention in the high-risk population for colorectal cancer (CRC).
METHODS
Meta-analysis was conducted to assess the caliber of the included literature by searching five databases for randomized controlled trials of DFMO chemoprevention in the high-risk population of CRC, with RevMan 5.4, Stata 15.0 and TSA 0.9.5.10 employed to statistically analyze the extracted data. Grade profiler 3.6 was employed for grading the evidence for the outcome indicators (disease progression and adenoma incidence).
RESULTS
Six trials were finally included in this research, with the collective data indicating that the DFMO combination therapy was efficacious in lowering the incidence of recurrent adenomas in patients who had experienced advanced CRC [RR 0.34, 95% CI 0.14 - 0.83, P < 0.05]. Meta-analysis showed that DFMO combined therapy had no statistical difference in disease progression in patients with familial adenomatous polyposis[RR 0.52, 95% CI 0.14 - 1.86, P > 0.05]; Trial Sequential Analysis reveals that the combination therapy of DFMO effectively diminishes the occurrence of recurrent adenomas in patients with a history of advanced colorectal tumors, displaying a Risk Ratio (RR) of 0.33 with a 95% Confidence Interval (CI) of 0.12 - 0.90 and a significance level of P < 0.05. This combination exhibits a statistically significant difference. Subgroup analysis demonstrates that, depending on the drug treatment regimen (DFMO+ Aspirin/DFMO+ Sulindac), the combination of DFMO and aspirin exhibits an effect comparable to a placebo in diminishing the occurrence of new adenomas in patients with a history of advanced colorectal tumors. However, the combination of DFMO and sulindac significantly mitigates the incidence of recurrent adenomas in this patient population.
CONCLUSION
This meta-analysis indicates that the existing randomized controlled trials are adequate to ascertain the efficacy of DFMO combination therapy in diminishing the incidence of recurrent adenomas in patients who have previously encountered advanced colorectal tumors. However, further clinical trials need to be conducted to evaluate the optimum dosage and treatment course of prophylactic implementation of DFMO combination therapy in high-risk populations.
PubMed: 38033490
DOI: 10.3389/fonc.2023.1281844