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International Journal of Molecular... Feb 2021The altered cell cycle is associated with aberrant growth factor signaling in somatotroph adenoma, which is the primary cause of acromegaly. The aim of the present study...
The altered cell cycle is associated with aberrant growth factor signaling in somatotroph adenoma, which is the primary cause of acromegaly. The aim of the present study was to investigate the pathological role of the INK4 family and evaluate the effectiveness of CDK4 inhibitor, palbociclib, in somatotroph adenoma. RNA‑Seq, RT‑PCR, and immunohistochemistry were applied to measure the levels and correlations of the INK4 family with angiogenesis, CDKs, EMT, and therapeutic targets. MTS, flow cytometry, and ELISA were used to investigate the bio‑activity in GH3 and GT1‑1 cell lines after palbociclib treatment. Compared with lactotroph adenoma, gonadotroph adenoma, and corticotroph adenoma, somatotroph samples demonstrated higher expression of CDKN2A and SSTR2 but a lower expression of EGFR, CDK4, and CDH2 (P<0.05). CDKN2A positively correlates with SSTR2, and negatively with CDK4, EGFR, and CDH2. Patients with lower CDKN2A had larger tumor size (P=0.016) and more invasive potential (P=0.023). Palbociclib inhibited cell proliferation, induced G1 phase arrest, reduced GH/IGF‑1 secretion of GH3 and GT1‑1 cell lines (P<0.05), and had a more prominent role in GH3 cells (P<0.05). CDKN2A inhibited the bio‑activity by modulating CDK4, and high CDKN2A predicted the insensitivity to CDK4 inhibitor, palbociclib, in somatotroph adenoma patients. In summary, the present study shows CDKN2A inhibited the bio‑activity by modulating CDK4, and high CDKN2A predicts the insensitivity to CDK4 inhibitor, Palbociclib, in somatotroph adenoma patients.
Topics: Adenoma; Adult; Antineoplastic Agents; Cell Line, Tumor; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase Inhibitor p16; Female; G1 Phase Cell Cycle Checkpoints; Growth Hormone-Secreting Pituitary Adenoma; Humans; Male; Middle Aged; Piperazines; Pyridines
PubMed: 33416096
DOI: 10.3892/ijmm.2020.4807 -
Reviews in Endocrine & Metabolic... Jun 2020Pituitary tumors are not rare if prevalence rates from autopsy or radiological series are considered; approximately 0.5% of all pituitary adenomas will come to medical... (Review)
Review
Pituitary tumors are not rare if prevalence rates from autopsy or radiological series are considered; approximately 0.5% of all pituitary adenomas will come to medical attention. Less than 0.1% of these pituitary adenomas will become malignant, and probably around 0.5% of all detected adenomas will display an aggressive course. However, the exact incidence of both aggressive pituitary adenomas and pituitary carcinomas is unknown, as most data come from series with selected patients, such as surgically treated patients, which is likely not a reflection of all patients with a pituitary adenoma. An aggressive pituitary adenoma is not well-defined; even though an overarching definition, capturing both immunohistochemical and clinical characteristics is probably not waterproof, adoption of a widely accepted definition will be very helpful to harmonize research and establish more reliable epidemiological data.
Topics: Adenoma; Humans; Neoplasm Invasiveness; Pituitary Neoplasms
PubMed: 32361816
DOI: 10.1007/s11154-020-09556-7 -
Computational Intelligence and... 2022The first-line treatment for patients with any type of pituitary adenoma is trans-sphenoidal surgery. Considering the prevalence of the condition globally, the treatment... (Meta-Analysis)
Meta-Analysis Review
Recurrence Rate and Exploration of Clinical Factors after Pituitary Adenoma Surgery: A Systematic Review and Meta-Analysis based on Computer Artificial Intelligence System.
BACKGROUND
The first-line treatment for patients with any type of pituitary adenoma is trans-sphenoidal surgery. Considering the prevalence of the condition globally, the treatment is quite common. The recurrence of pituitary adenoma is a recognized occurrence in the medical field; however, there is limited comprehensive research and analysis of the predictive factors of recurrence rates and the clinical factors impacting relapse rates. Identifying the recurrence rates of pituitary adenomas and the clinical factors associated with them could help increase the remission rate by increasing focus on the specific aspects for early diagnosis and improved treatment.
OBJECTIVE
The objective of the current systematic review and meta-analysis is to assess the recurrent rates based on previous studies and to explore the clinical factors after pituitary surgery.
METHODS
A search was performed on PubMed, APA PsycINFO, Scopus, CENTRAL, and Google Scholar databases for English articles published from 1 January 2010 to 1 August 2022. Systematic reviews, meta-analysis, evidence syntheses, editorials, commentaries, preclinical studies, abstracts, theses, and preprints were excluded. Meta XL statistical software was used to conduct a prevalence meta-analysis.
RESULTS
PubMed, PsycINFO, and Medline databases were searched. All of the articles were written between 2012 and 2022. In the beginning, 612 items were recognized. After removing duplicates and analyzing the remaining articles in terms of inclusion and exclusion criteria, 31 articles remained.
CONCLUSION
There is a relationship between recurrence rates and the follow-up period. There were conflicting results about the clinical factors after pituitary adenoma surgery, specifically age and tumor size. Some included studies that there was an association between macroadenomas and high recurrence rates. No study reported that gender was a clinical factor affecting pituitary adenoma surgery outcomes or the recurrence rate. Studies also reported that there was a correlation between the remnant tumor factor and the recurrence rates; adenoma remnants after surgery increased the risk of recurrence rates for patients.
Topics: Humans; Pituitary Neoplasms; Artificial Intelligence; Adenoma; Computers
PubMed: 36275975
DOI: 10.1155/2022/6002672 -
BMC Cancer Oct 2023Accumulating studies have suggested metabolic syndrome (MetS) contributed to colorectal cancer (CRC) development. However, advanced CRC might decrease the detection...
BACKGROUND
Accumulating studies have suggested metabolic syndrome (MetS) contributed to colorectal cancer (CRC) development. However, advanced CRC might decrease the detection proportion of MetS due to chronic malnutrition, we included patients with early-stage CRC to examine the associations among MetS, onset age, and different tumorigenesis pathways of CRC.
METHODS
We conducted a retrospective study that included 638 patients with early-stage CRC from January 2014 to December 2018. Patient information was collected from the medical record system and further refined during the follow-up. Stratified analyses of the associations between MetS and different stratification factors were determined by the Cochran‒Mantel‒Haenszel test.
RESULTS
There were 16 (13.3%) and 111 (21.4%) cases suffering from MetS in the early-onset and late-onset CRC groups, respectively. MetS coexisted in early-stage CRC patients ≥ 50 years of age more frequently than patients < 50 years of age (OR 1.77; 95% CI 1.01 to 3.12), but not for women patients (OR 0.84; 95% CI 0.79 to 0.90). MetS patients were associated with a higher risk of advanced serrated lesions than that of conventional adenomas (OR 1.585; 95% CI 1.02 to 2.45), especially in patients ≥ 50 years (OR 1.78; 95% CI 1.11 to 2.85).
CONCLUSIONS
Metabolic dysregulation might partly contribute to the incidence of colorectal serrated lesions. Prevention of MetS should be highly appreciated in the early diagnosis and early treatment of the colorectal cancer system, especially in patients ≥ 50 years.
Topics: Humans; Female; Middle Aged; Metabolic Syndrome; Retrospective Studies; Adenoma; Colorectal Neoplasms; Incidence; Risk Factors; Colonoscopy
PubMed: 37872512
DOI: 10.1186/s12885-023-11537-3 -
Gut Microbes 2021Colorectal cancer (CRC) is a heterogeneous disease with different gene expression patterns. There are two major colorectal carcinogenesis pathways: conventional... (Review)
Review
Colorectal cancer (CRC) is a heterogeneous disease with different gene expression patterns. There are two major colorectal carcinogenesis pathways: conventional adenoma-carcinoma pathway and alternative serrated neoplasia pathway. Apart from the conventional pathway that is typically initiated by characteristic mutation and chromosomal instability, the serrated neoplasia pathway is mainly characterized by mutations of or , microsatellite instability (MSI), and CpG island methylator phenotype (CIMP). Despite the malignant potential of serrated lesions, they can be easily overlooked during endoscopy screening and even in pathological assessment due to its anatomical location, morphology, and histological features. It has been shown that environmental factors especially the gut microbial composition play a key role in CRC pathogenesis. Thus, the preferential localization of serrated lesions in specific intestine areas suggest that niche-specific microbiota composition might intertwined with host genetic perturbations during the development of serrated lesions. Although serrated lesions and conventional adenomas are biologically different, most studies have focused on conventional adenomas, while the pathophysiology and role of microorganisms in the development of serrated lesions remain elusive. In this review, we discuss on the role of gut microbiota in the serrated neoplasia pathway of colorectal carcinogenesis and its specific clinical and molecular features, and summarize the potential mechanisms involved.
Topics: Adenoma; Carcinogenesis; Colorectal Neoplasms; Dysbiosis; Gastrointestinal Microbiome; Humans; Mutation; Precancerous Conditions
PubMed: 33382354
DOI: 10.1080/19490976.2020.1863135 -
Endoscopy Dec 2023Texture and color enhancement imaging (TXI) was recently proposed as a substitute for standard high definition white-light imaging (WLI) to increase lesion detection... (Randomized Controlled Trial)
Randomized Controlled Trial Clinical Trial
BACKGROUND
Texture and color enhancement imaging (TXI) was recently proposed as a substitute for standard high definition white-light imaging (WLI) to increase lesion detection during colonoscopy. This international, multicenter randomized trial assessed the efficacy of TXI in detection of colorectal neoplasia.
METHODS
Consecutive patients aged ≥ 40 years undergoing screening, surveillance, or diagnostic colonoscopies at five centers (Italy, Germany, Japan) between September 2021 and May 2022 were enrolled. Patients were randomly assigned (1:1) to TXI or WLI. Primary outcome was adenoma detection rate (ADR). Secondary outcomes were adenomas per colonoscopy (APC) and withdrawal time. Relative risks (RRs) adjusted for age, sex, and colonoscopy indication were calculated.
RESULTS
We enrolled 747 patients (mean age 62.3 [SD 9.5] years, 50.2 % male). ADR was significantly higher with TXI (221/375, 58.9 %) vs. WLI (159/372, 42.7 %; adjusted RR 1.38 [95 %CI 1.20-1.59]). This was significant for ≤ 5 mm (RR 1.42 [1.16-1.73]) and 6-9 mm (RR 1.36 [1.01-1.83]) adenomas. A higher proportion of polypoid (151/375 [40.3 %] vs. 104/372 [28.0 %]; RR 1.43 [1.17-1.75]) and nonpolypoid (136/375 [36.3 %] vs. 102/372 [27.4 %]; RR 1.30 [1.05-1.61]) adenomas, and proximal (143/375 [38.1 %] vs. 111/372 [29.8 %]; RR 1.28 [1.05-1.57]) and distal (144/375 [38.4 %] vs. 98/372 [26.3 %]; RR 1.46 [1.18-1.80]) lesions were found with TXI. APC was higher with TXI (1.36 [SD 1.79] vs. 0.89 [SD 1.35]; incident rate ratio 1.53 [1.25-1.88]).
CONCLUSIONS
TXI increased ADR and APC among patients undergoing colonoscopy for various indications. TXI increased detection of polyps < 10 mm, both in the proximal and distal colon, and may help to improve colonoscopy quality indicators.
Topics: Humans; Male; Middle Aged; Female; Colorectal Neoplasms; Colonoscopy; Polyps; Adenoma; Colonic Polyps
PubMed: 37451283
DOI: 10.1055/a-2129-7254 -
Neurology India 2020Pituitary adenomas are one of the common indications for gamma knife radiosurgery. Gamma knife enables one to deliver a very high radiation dose to the target in a... (Review)
Review
Pituitary adenomas are one of the common indications for gamma knife radiosurgery. Gamma knife enables one to deliver a very high radiation dose to the target in a single fraction. Due to steep radiation fall out of Gamma Knife, the adjacent visual apparatus gets minimal radiation. The aim of stereotactic radiosurgery for pituitary adenomas is to stop tumor growth, normalize hormonal hypersecretion, preserve pituitary function, and protect important surrounding structures. Surgery is the treatment modality of choice in the management of pituitary adenomas and gamma knife radiosurgery is restricted for residual or recurrent lesions only. The acceptable marginal dose for non-functional adenomas is 12 Gy. Control rates varies from 76-87% at 10 years are described in non-functional pituitary adenomas. In functional adenomas, to achieve hormonal remission a higher marginal dose up to 25 Gy is needed. However, primary gamma knife radiosurgery is needed in some situations - for instance, when the patient is unfit for surgery due to various reasons or surgical difficulties like the presence of kissing carotids.
Topics: Adenoma; Disease Progression; Humans; Pituitary Neoplasms; Radiosurgery; Treatment Outcome
PubMed: 32611902
DOI: 10.4103/0028-3886.287674 -
Clinical and Translational... Aug 2023Patients with serrated polyposis syndrome (SPS) have an increased risk to develop colorectal cancer (CRC). Due to an abundance of serrated polyps, these CRCs are assumed...
INTRODUCTION
Patients with serrated polyposis syndrome (SPS) have an increased risk to develop colorectal cancer (CRC). Due to an abundance of serrated polyps, these CRCs are assumed to arise mainly through the serrated neoplasia pathway rather than through the classical adenoma-carcinoma pathway. We aimed to evaluate the pathogenetic routes of CRCs in patients with SPS.
METHODS
We collected endoscopy and pathology data on CRCs and polyps of patients with SPS under treatment in our center. Our primary end point was the proportion of BRAFV600E mutated CRCs, indicating serrated pathway CRCs (sCRCs). CRCs lacking BRAFV600E most likely inferred a classical adenoma-carcinoma origin (aCRCs). We assessed patient, polyp, and CRC characteristics and stratified for BRAFV600E mutation status.
RESULTS
Thirty-five patients with SPS harbored a total of 43 CRCs. Twenty-one CRCs (48.8%) carried a BRAFV600E mutation, 10 of which lacked MLH1 staining and 17 (81%) were located in the proximal colon. Twenty-two CRCs (51.1%) did not carry a BRAFV600E mutation and were MLH1 proficient. Of these 22 putatively aCRCs, 17 (77.3%) were located distally and one-third (36.4%) harbored a pathogenic KRAS or NRAS mutation. In patients with BRAFwt -CRCs, a higher ratio of the median number of conventional adenomas versus serrated polyps was found (4 vs 13) than patients with BRAFV600E -CRCs (1 vs 14).
DISCUSSION
Our study indicates that in patients with SPS, the ratio of sCRCs:aCRCs on average is 50:50. This elevated sCRC:aCRC ratio in patients with SPS, when compared with non-SPS patients, correlates well with the differences in the ratios of the numbers of sessile serrated lesions and conventional adenomas in patients with SPS and non-SPS patients, respectively.
Topics: Humans; Colonic Polyps; Colorectal Neoplasms; Adenomatous Polyposis Coli; Adenoma; Carcinoma
PubMed: 37352472
DOI: 10.14309/ctg.0000000000000611 -
United European Gastroenterology Journal Oct 2022Widespread adoption of optical diagnosis of colorectal neoplasia is prevented by suboptimal endoscopist performance and lack of standardized training and competence... (Review)
Review
Widespread adoption of optical diagnosis of colorectal neoplasia is prevented by suboptimal endoscopist performance and lack of standardized training and competence evaluation. We aimed to assess diagnostic accuracy of endoscopists in optical diagnosis of colorectal neoplasia in the framework of artificial intelligence (AI) validation studies. Literature searches of databases (PubMed/MEDLINE, EMBASE, Scopus) up to April 2022 were performed to identify articles evaluating accuracy of individual endoscopists in performing optical diagnosis of colorectal neoplasia within studies validating AI against a histologically verified ground-truth. The main outcomes were endoscopists' pooled sensitivity, specificity, positive and negative predictive value (PPV/NPV), positive and negative likelihood ratio (LR) and area under the curve (AUC for sROC) for predicting adenomas versus non-adenomas. Six studies with 67 endoscopists and 2085 (IQR: 115-243,5) patients were evaluated. Pooled sensitivity and specificity for adenomatous histology was respectively 84.5% (95% CI 80.3%-88%) and 83% (95% CI 79.6%-85.9%), corresponding to a PPV, NPV, LR+, LR- of 89.5% (95% CI 87.1%-91.5%), 75.7% (95% CI 70.1%-80.7%), 5 (95% CI 3.9%-6.2%) and 0.19 (95% CI 0.14%-0.25%). The AUC was 0.82 (CI 0.76-0.90). Expert endoscopists showed a higher sensitivity than non-experts (90.5%, [95% CI 87.6%-92.7%] vs. 75.5%, [95% CI 66.5%-82.7%], p < 0.001), and Eastern endoscopists showed a higher sensitivity than Western (85%, [95% CI 80.5%-88.6%] vs. 75.8%, [95% CI 70.2%-80.6%]). Quality was graded high for 3 studies and low for 3 studies. We show that human accuracy for diagnosis of colorectal neoplasia in the setting of AI studies is suboptimal. Educational interventions could benefit by AI validation settings which seem a feasible framework for competence assessment.
Topics: Adenoma; Artificial Intelligence; Colonic Polyps; Colonoscopy; Colorectal Neoplasms; Humans; Narrow Band Imaging
PubMed: 35984903
DOI: 10.1002/ueg2.12285 -
Frontiers in Endocrinology 2023Parathyroid adenomas weighing more than 3.5 g are reported variously as "atypical", "large" or "giant" parathyroid adenomas. All such adenomas are rare variants...
Parathyroid adenomas weighing more than 3.5 g are reported variously as "atypical", "large" or "giant" parathyroid adenomas. All such adenomas are rare variants accounting for no more than 1.5% of all parathyroid adenomas. Large parathyroid adenomas are often associated with more severe form of the disease, including osteitis fibrosa cystica (OFC) and share many biochemical, histological, and molecular features of both benign and malignant parathyroid neoplasms, and are considered a distinct clinical entity. However, the pathogenesis of oversized parathyroid adenomas and the often-associated skeletal phenotype remains unclear. We present 5 cases of primary hyperparathyroidism (PHPT) with OFC, an uncommon manifestation of contemporary PHPT, associated with larger parathyroid adenomas, seen in the Bone and Mineral Disorders Clinic of the Henry Ford Health in the last 30 years to illustrate the critical role of vitamin D nutrition in the pathogenesis of both the OFC and adenoma size. The estimated prevalence of OFC was very low 0.2%, 5 of the >3000 surgically confirmed cases of PHPT seen during this time. The mean ± SD values were: age: 36.8 ± 22.1 years (4 of the 5 <36years), serum calcium 11.6 ± 1.1 mg/dl, alkaline phosphatase 799 ± 487 IU/L, PTH 1440 ± 477 pg/ml, 25-hydroxyvitamin D 13.0 ± 8.9 ng/ml, 1,25-dihyroxyvitamin D 26.5 ± 13.7 pg/ml, urine calcium 562 ± 274 mg/day, and parathyroid adenoma weight 4.53 ± 2.2 g. Parathyroidectomy led to the resolution of both the biochemical indices and OFC in each patient without recurrence over >10 years of follow-up. Because OFC is a very rare in the West, but very common areas of endemic vitamin D deficiency, we also examined the relationship between vitamin D nutrition, as assessed by serum 25-hydroxyvitamin D level, and parathyroid adenoma weight as well as prevalence of OFC in two large secularly diverse cohorts of patients with PHPT (Detroit, USA and Chandigarh, India). Based on this relationship and the relative prevalence of OFC in these two large cohorts, we propose that vitamin D nutrition (and perhaps calcium nutrition) best explains both the adenoma size and prevalence of OFC.
Topics: Humans; Parathyroid Neoplasms; Calcium; Parathyroid Hormone; Vitamin D; Adenoma; Calcifediol; Osteitis Fibrosa Cystica; Phenotype
PubMed: 36817587
DOI: 10.3389/fendo.2023.1009516