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Background: Surgery for giant pituitary adenomas (GPAs) poses significant challenges, particularly when the tumor cannot be fully addressed using either the endoscopic endonasal approach (EEA) or the microscopic transcranial approach (MTCA) alone., Method: We utilized two combined approaches for complex GPAs: 1) expanded endoscopic endonasal approach (EEEA) combined with microscopic pterional approach (MPA), and 2) EEEA combined with endoscopic transventricular approach (ETVA)., Conclusion: The combined approach is an effective surgical technique for complex GPAs. The EEEA-MPA approach is suitable for GPAs with superior and lateral extension, while the EEEA-ETVA approach is beneficial for tumors with lateral ventricular invasion., Competing Interests: Declarations. Ethical approval: The Ethics Committee on Biomedical Research, West China Hospital of Sichuan University, approved the ethical review of the study (No.453). Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Colorectal cancer (CRC) development involves a series of molecular events that drive the progression from normal colorectal epithelium to adenoma and eventually to invasive carcinoma. While the involvement of extrachromosomal circular DNAs (ecDNAs) in cancer genome remodeling has been established, their specific roles in CRC formation remain unclear. Using Circle-Sequencing and whole transcriptomic sequencing, we comprehensively profile circular DNAs and transcriptomes in healthy individuals, colorectal adenoma, and CRC patients. Our delineate analyses characterize the key circular DNAs involved in oncogene expression through the normal-adenoma-carcinoma continuum and highlight that immune response-related pathways and cell cycle pathways, are the dominat events in CRC progression. Notably, chr8 ecDNA 64950741-114379093 exhibits robust up-regulation during CRC progression. Further validation in a new cohort of 50 CRC patients confirms the higher expression of chr8 ecDNA 64950741-114379093 and its strong correlation with poor prognosis. Thus, these findings provide unprecedented insights into the landscape of circular DNAs in CRC and highlights the potential of chr8 ecDNA 64950741-114379093 as a promising biomarker and therapeutic target for CRC management., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Context: Few data exist about the clinical course of acromegaly, surgical and medical outcomes in patients with GH- and prolactin cosecreting pituitary adenomas (GH&PRL-PAs). Nevertheless, some series described a more aggressive clinic-radiological behavior than in growth hormone-secreting pituitary adenomas (GH-PAs)., Objective: This work aims to evaluate differences in clinical presentation and in surgical outcomes between GH-PAs and GH&PRL-PAs., Methods: A multicenter retrospective study was conducted of 604 patients with acromegaly who underwent pituitary surgery. Patients were classified into 2 groups according to serum PRL levels at diagnosis and immunohistochemistry (IHC) for PRL: a) GH&PRL-PAs when PRL levels were above the upper limit of normal (ULN) and IHC for GH and PRL was positive or PRL levels were greater than 100 ng/dL and PRL IHC was not available (n = 130) and b) GH-PA patients who did not meet the previously mentioned criteria (n = 474)., Results: GH&PRL-PAs represented 21.5% (n = 130) of patients with acromegaly. The mean age at diagnosis was lower in GH&PRL-PAs than in GH-PAs (P < .001). GH&PRL-PAs were more frequently macroadenomas (90.6% vs 77.4%; P = .001) and tended to be more invasive (33.6% vs 24.7%; P = .057) than GH-PAs. Furthermore, they had presurgical hypopituitarism more frequently (odds ratio 2.8; 95% CI, 1.83-4.38). Insulin-like growth factor ULN levels at diagnosis were lower in patients with GH&PRL-PAs (median 2.4 [interquartile range (IQR) 1.73-3.29] vs 2.7 [IQR 1.91-3.67]; P = .023). There were no differences in the immediate (41.1% vs 43.3%; P = .659) or long-term postsurgical acromegaly biochemical cure rate (53.5% vs 53.1%; P = .936) between groups. However, there was a higher incidence of permanent arginine-vasopressin deficiency (AVP-D) (7.3% vs 2.4%; P = .011) in GH&PRL-PA patients., Conclusion: GH&PRL-PAs are responsible for 20% of acromegaly cases. These tumors are more invasive, larger, and cause hypopituitarism more frequently than GH-PAs and are diagnosed at an earlier age. The biochemical cure rate is similar between both groups, but patients with GH&PRL-PAs tend to develop permanent postsurgical AVP-D more frequently., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective Surgery is recommended for large pedunculated gallbladder polyps (PGPs), which measure 10 mm or more in size, because they tend to be neoplastic polyps (NPs), such as adenomas and adenocarcinomas. However, after resection, they are often found to be non-neoplastic polyps (non-NPs). This study aimed to evaluate the usefulness of plain computed tomography (CT) in distinguishing NPs from non-NPs. Methods Of the 80 patients who underwent cholecystectomy for PGPs ≥10 mm between January 2008 and February 2021, 46 who underwent plain and contrast-enhanced CT (CE-CT) before resection were included in this study. We retrospectively assessed the polyp detection rate (PDR) using CT and calculated the difference in the CT values between PGPs and the surrounding bile. Results Twenty-one patients had NPs (12 adenomas, 5 carcinomas in adenoma, and 4 adenocarcinomas). The others were non-NPs (24 cholesterol polyps and one hyperplastic polyp). The PDR using plain CT was significantly higher in the NP group than in the non-NP group (38% (8/21) vs. 0% (0/25), p <0.01). The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of NPs were 38%, 100%, 100%, 66%, and 72%, respectively. The difference in the CT values between PGPs and the surrounding bile was significantly larger in the NP group than in the non-NP group (14.12 ± 11.38 HU, 5.04 ± 6.15 HU, p <0.01). Conclusions PGPs detected using plain CT had a high probability of being NPs. Plain CT is therefore considered to be useful for differentiating NPs from non-NPs.

Objectives: Serrated polyps (SPs) with synchronous advanced adenoma (AA) may increase the incidence of colorectal cancer. However, current studies do not address this combination of SPs and AAs in detail with regard to their clinical characteristics in different age groups. The aim was to assess clinical characteristics and risk factors for SPs with synchronous AA in different age groups., Design: Retrospective cohort study., Setting: Electronic medical record data from January 2011 to January 2022 at three grade III class A hospitals were enrolled in the study., Participants: A total of 1605 patients with SPs with synchronous AA, including 484 patients in the elderly group and 1121 patients in the non-elderly group, were studied., Main Exposure Measure: The elderly group and the non-elderly group., Main Outcome Measure: Sex, smoking history, drinking history, body mass index (BMI), SP location, size, morphology and pathology., Results: The incidence of hyperplastic polyps (HPs) with synchronous AA in the elderly group was higher than that in the non-elderly group, while the incidence of sessile serrated adenomas/polyps (SSAs/Ps) with synchronous AA in the non-elderly group was higher than that in the elderly group. Male sex, drinking history and HP size (≤20 mm) were independent risk factors for HPs with synchronous AA in the non-elderly group, while drinking history and HP size (≤15 mm) were independent risk factors in the elderly group. For SSAs/Ps with synchronous AA, male sex, smoking history, drinking history, and SSA size (≥16 mm) were independent risk factors in the non-elderly group; high BMI was an independent risk factor in the elderly group., Conclusions: SPs with synchronous AA showed different clinical characteristics and risk factors in different age groups., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Primary hyperparathyroidism is an endocrine disease and a common cause of nonmalignant hypercalcemia, often discovered incidentally in asymptomatic patients. The case reported herein illustrates that significant hormonal imbalances can present with unexpectedly mild clinical manifestations., Case Presentation: We describe a 47-year-old Caucasian male with two episodes of kidney stones and otherwise no symptoms of severe hypercalcemia. In our case, fasting emerged as a potential risk factor for the development of renal stones. The diagnosis was primary hyperparathyroidism. The intervention consisted of preoperative fluids and cinacalcet while awaiting surgery. Despite initial stability, the patient experienced a subsequent increase in ionized calcium and parathyroid hormone levels, becoming symptomatic with fatigue, tremors, and heart palpitations. This progression led to a diagnosis of a hypercalcemic crisis, and the plan was accelerated. An acute parathyroid scintigraphy and an ultrasound was performed and revealed a giant intrathoracic parathyroid adenoma. After surgical removal of the adenoma, he developed hungry bones and biochemical remission. The patient has received three extracorporeal shock wave lithotripsy treatments for a stone in the upper left kidney, but as of a computed tomography scan on 9 February 2024, the stone remains unchanged. Owing to the stone's resistance to extracorporeal shock wave lithotripsy and the absence of symptoms, no further treatment is planned. Endoscopic laser treatment (retrograde intrarenal surgery) is an option, but for now, the situation will be monitored., Conclusion: This case report underscores that extremely elevated levels of calcium and parathyroid hormone along with a rare giant parathyroid adenoma may not necessarily present with symptoms indicative of a calcium crisis. Additionally, management of such rare giant parathyroid adenomas requires careful monitoring and a tailored approach to address potential postsurgical complications such as hungry bone syndrome., Competing Interests: Declarations Ethics approval and consent to participate Ethical approval was not required for this case report as it pertains to a single patient´s treatment and outcome, and no experimental procedures were involved. The patient provided informed consent for the treatment and the publication of their case details. All patient information has been anonymized to protect privacy. Consent for publication Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Competing interests All authors state that they have no competing interests, (© 2024. The Author(s).)

Standard-of-care (SoC) imaging for assessing colorectal polyps during colonoscopy, based on white-light colonoscopy (WLC) and narrow-band imaging (NBI), does not have sufficient accuracy to assess the invasion depth of complex polyps non-invasively during colonoscopy. We aimed to evaluate the feasibility of a custom endoscopic optical coherence tomography (OCT) probe for assessing colorectal polyps during routine colonoscopy. Patients referred for endoscopic treatment of large colorectal polyps were enrolled in this pilot clinical study, which used a side-viewing OCT catheter developed for use with an adult colonoscope. OCT images of polyps were captured during colonoscopy immediately before SoC treatment. A deep learning model was trained to differentiate benign from deeply invasive lesions for real-time diagnosis. 35 polyps from 32 patients were included. OCT imaging added on average 3:40 min (range 1:54-8:20) to the total procedure time. No complications due to OCT were observed. OCT revealed distinct subsurface tissue structures that correlated with histological findings, including tubular adenoma (n = 20), tubulovillous adenoma (n = 10), sessile serrated polyps (n = 3), and invasive cancer (n = 2). The deep learning model achieved an area under the receiver operating characteristic curve (AUROC) of 0.984 (95%CI 0.972-0.996) and Cohen's kappa of 0.845 (95%CI 0.774-0.915) when compared to gold standard histopathology. OCT is feasible and safe for polyp assessment during routine colonoscopy. When combined with deep learning, OCT offers clinicians increase confidence in identifying deeply invasive cancers, potentially improving clinical decision-making. Compared to previous studies, ours offers a nuanced comparison between not just benign and malignant lesions, but across multiple histological subtypes of polyps., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: To investigate the factors affecting visual field recovery in patients with pituitary adenoma following surgical removal, both eyes of 35 patients with pituitary adenoma who had been followed up for > six months post-surgery were retrospectively analyzed., Material and Methods: Pre- and post-operative visual acuity, visual field test, retinal nerve fiber layer (RNFL), and ganglion cell inner plexiform layer (GCIPL) thickness were investigated. The average age of the 35 patients was 58.3 ± 11.5 years. Preoperatively, 30 eyes (mean average RNFL thickness, 99.73 ± 5.89 μm) and 40 eyes (mean average RNFL thickness, 77.55 ± 8.35 μm) were included in the thick (≥ 90 μm) and thin RNFL group (< 90 μm), respectively., Results: In the thick RNFL group, pre- and post-operative mean deviation (MD) and pattern standard deviation (PSD) were favorable (all p < 0.001), and the proportion of eyes of postoperative MD change which were stable or improved was greater than in the thin RNFL group (p = 0.042). Preoperative MD, RNFL (except nasal quadrant) and GCIPL thickness were positively correlated to postoperative MD values (all, p < 0.05). Preoperative MD and temporal RNFL thickness were significantly correlated with postoperative MD change rate (p = 0.03 and 0.04, respectively). Preoperative GC IPL thickness and postoperative MD change rate were not significantly correlated (p = 0.61). Using univariate regression analysis, preoperative best corrected visual acuity (Odds ratio [OR], 0.050; p < 0.001), tumor volume (OR, 1.110, p = 0.002), higher preoperative MD values (OR, 0.858; p < 0.001), lower preoperative PSD values (OR, 1.169, p = 0.002), thick RNFL (OR, 0.215; p = 0.003) and thick GCIPL (OR, 0.305, p = 0.018) were significantly associated with a good visual field outcome following surgery. According to multivariate analysis, any other parameters were not significant. In patients with thick RNFL, postoperative MD values were better than in the thin RNFL group., Conclusions: Eyes with preoperative higher MD and thick temporal RNFL showed more improvement in their visual fields postoperative. Preoperative thick RNFL could be a potential predictor of visual field recovery following TSA-TR, while macular GCIPL thickness does not appear to be a reliable predictor., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Han et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Aim: Randomised trials show improved polyp detection with computer-aided detection (CADe), mostly of small lesions. However, operator and selection bias may affect CADe's true benefit. Clinical outcomes of increased detection have not yet been fully elucidated., Methods: In this multicentre trial, CADe combining convolutional and recurrent neural networks was used for polyp detection. Blinded endoscopists were monitored in real time by a second observer with CADe access. CADe detections prompted reinspection. Adenoma detection rates (ADR) and polyp detection rates were measured prestudy and poststudy. Histological assessments were done by independent histopathologists. The primary outcome compared polyp detection between endoscopists and CADe., Results: In 946 patients (51.9% male, mean age 64), a total of 2141 polyps were identified, including 989 adenomas. CADe was not superior to human polyp detection (sensitivity 94.6% vs 96.0%) but outperformed them when restricted to adenomas. Unblinding led to an additional yield of 86 true positive polyp detections (1.1% ADR increase per patient; 73.8% were <5 mm). CADe also increased non-neoplastic polyp detection by an absolute value of 4.9% of the cases (1.8% increase of entire polyp load). Procedure time increased with 6.6±6.5 min (+42.6%). In 22/946 patients, the additional detection of adenomas changed surveillance intervals (2.3%), mostly by increasing the number of small adenomas beyond the cut-off., Conclusion: Even if CADe appears to be slightly more sensitive than human endoscopists, the additional gain in ADR was minimal and follow-up intervals rarely changed. Additional inspection of non-neoplastic lesions was increased, adding to the inspection and/or polypectomy workload., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Liquid biopsy has an underexplored diagnostic potential in colorectal cancer (CRC). Sufficient quantity and quality of its elements (circulating cell-free DNA (ccfDNA), exosomes and exosomal RNA) are essential for accurate results. The present study aims to establish the optimal protocol for handling liquid biopsy samples. Samples were obtained by collecting peripheral blood from colorectal adenoma patients in CellSave tubes. Plasma was separated within six hours using differential centrifugation and aliquots stored at - 20/- 80 °C until further processing. Three methods for isolation of ccfDNA, and two combinations of kits for isolation of exosomes and exosomal RNA were tested. The quality and quantity of ccfDNA isolates were evaluated. Exosomes were characterised by determining size, concentration, and total and specific protein content. Expression of chosen microRNAs, miR-19a-3p and miR-92-3p, which have been implicated in CRC progression, were determined. The vacuum-column-based kit showed the highest quantities of isolated ccfDNA (P-value < 0.001). Kits for exosome isolation significantly differed in size (P-value = 0.016), concentration (P-value = 0.016) and protein content (P-value = 0.016). There was no significant difference in expressions of miR-19a-3p (P-value = 0.219) and miR-92a-3p (P-value = 0.094) between the two isolation kits. The new, adapted protocol described, enables simultaneous analysis of multiple elements when investigating potential biomarkers of CRC., (© 2024. The Author(s).)

Background: Follicular thyroid carcinoma (FTC) is the second most common cancer of the thyroid gland and has a greater propensity for haematogenous metastasis. However, the preoperative differentiation of FTC from follicular thyroid adenoma (FTA) is not well established. Certain ultrasound characteristics are associated with an increased risk of thyroid malignancy, but mainly for papillary thyroid cancers and not for FTC., Objectives: This retrospective study aimed to evaluate the ultrasound characteristics of FTC and the value of ultrasound characteristics in differentiating FTC from FTA., Methods: A total of 96 patients with pathologically confirmed FTC or FTA who underwent preoperative thyroid ultrasound were included in this study. The ultrasound and pathological characteristics were evaluated., Results: Our data revealed that the incidences of lesions with tubercle-in-nodule, spiculated/microlobulated margins, mixed vascularization, egg-shell calcification, central stellate scarring, extension toward the capsule and chronic lymphocytic thyroiditis were significantly higher in the FTC group (all p < 0.05). After adjusting for confounding factors, lesions with mixed vascularization (odds ratio [OR]: 2.038, P = 0.019), central stellate scarring (OR: 87.992, P = 0.007), extension toward the capsule (OR: 22.587, P = 0.010), and chronic lymphocytic thyroiditis (OR: 9.195, P = 0.006) were independently associated with FTC. Furthermore, combined with chronic lymphocytic thyroiditis, mixed vascularization, central stellate scarring, and extension toward the capsule showed high discriminatory accuracy in predicting FTC (AUC: 0.914; sensitivity: 96.5%; specificity: 71.8%; p < 0.001)., Conclusions: In combination with chronic lymphocytic thyroiditis, mixed vascularization, central stellate scarring, and extension toward the capsule have greater accuracy in differentiating FTCs from FTAs., (© 2024. The Author(s).)

Objectives: The incidence of pituitary neuroendocrine tumors has been reported high at autopsy. This study aimed to detect many tumors in both anterior and posterior lobes to prove tumor histogenesis., Methods: In total, 150 pituitary glands were studied from the University of Kansas Medical Center from 1995 to 2000. The pituitary gland was sagittally sliced from anterior to posterior into 6 to 8 sections. When H&E-stained sections revealed tumors, the tumors were immunohistochemically stained for 6 pituitary hormones., Results: Among 150 autopsy cases, 38 (25.3%) harbored microadenomas, including 4 cases with double tumors. Twenty-three (54.7%) cases were negative to all pituitary hormones. Of the remaining 19 tumors, 13 (30.9%) were lactotrophs, with 4 cases being concomitantly somatotrophs and gonadotrophs, and 2 cases were corticotropes. More than 85% of pituitary neuroendocrine tumors were adjacent to the capsule. Thirteen (8.7%) granular cell pituicytomas were found in the posterior lobe. There were pituicytes transforming into granular cell tumors., Conclusions: The incidence was 25.3% for pituitary neuroendocrine tumors and 8.7% for granular cell pituicytomas. Since most pituitary neuroendocrine tumors were adjacent to the pituitary capsule, the capsule appeared to be the germinal center. Both pituitary tumors belonged to the 2 different transcription factor lineages., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Managing nonfunctioning pituitary adenomas (NFPAs) is difficult due to limited drug treatments. Cabergoline's (CAB) effectiveness for NFPAs is debated. This study explores the role of HTR2B in NFPAs and its therapeutic potential., Methods: We conducted screening of bulk RNA-sequencing data to analyze HTR2B expression levels in NFPA samples. In vitro and in vivo experiments were performed to evaluate the effects of HTR2B modulation on tumor growth and cell cycle regulation. Mechanistic insights into the HTR2B-mediated signaling pathway were elucidated using pharmacological inhibitors and molecular interaction assays., Results: Elevated HTR2B expression was detected in NFPA samples, which was associated with increased tumor survival. Inhibition of HTR2B activity resulted in the suppression of tumor growth through modulation of the G2M cell cycle. The inhibition of HTR2B with PRX-08066 was found to block STAT3 phosphorylation and nuclear translocation by interfering with the Gαq/PLC/PKC pathway. A direct interaction between PKC-γ and STAT3 was critical for STAT3 activation. CAB was shown to activate pSTAT3 via HTR2B, reducing its therapeutic potential. However, the combination of an HTR2B antagonist with CAB significantly inhibited tumor cell proliferation in HTR2B-expressing pituitary tumor cell lines, a xenografted pituitary tumor model, and patient-derived samples. Analysis of patient-derived data indicated that a distinct molecular pattern characterized by upregulated HTR2B/PKC-γ and downregulated BTG2/GADD45A may benefit from combination treatment with CAB and PRX-08066., Conclusions: HTR2B is a potential therapeutic target for NFPAs, and its inhibition could improve CAB efficacy. A dual therapy approach may be beneficial for NFPA patients with high HTR2B expression., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background/aims: Colorectal cancer (CRC) is one of the deadliest cancers worldwide, mostly arising from adenomatous polyps. Mounting evidence has demonstrated that changes in the gut microbiome play key roles in CRC progression, while quite few studies focused on the altered microbiota architecture of advanced adenoma (AA), a crucial precancerous stage of CRC. Thus, we aimed to investigate the microbial profiles of AA patients., Materials and Methods: Fecal samples were collected from 26 AA patients and 26 age- and sex-matched normal controls (NC), and analyzed by shotgun metagenomic sequencing., Results: Gut microbial dysbiosis was observed in AA patients with lower alpha diversity. Advanced adenoma was characterized by an increased Bacillota/Bacteroidota ratio and higher Pseudomonadota levels compared to normal individuals. Linear discriminant analysis effect size (LEfSe) analysis was performed and identified 14 microbiota with significantly different abundance levels between AA and NC groups. Functional analysis revealed that tryptophan metabolism was upregulated in AA. Correspondingly, the expressions of gut microbes implicated in tryptophan metabolism also changed, including Akkermansia muciniphila, Bacteroides ovatus, Clostridium sporogenes, and Limosilactobacillus reuteri. The microbial network suggested that AA exhibited decreased correlation complexity, with Escherichia coli and Enterobacteriaceae unclassified harboring the strongest connectivity. A diagnostic model consisting of 3 microbial species was established based on random forest, yielding an area under the curve (AUC) of 0.799., Conclusion: Our study profiled the alterations of the gut microbiome in AA patients, which may enrich the knowledge of microbial signatures along with colorectal tumorigenesis and provide promising biomarkers for AA diagnosis.

Background: Coexisting parathyroid adenoma, thyroid carcinoma, and tuberculosis of thyroid is a very rare phenomenon. Primary thyroid tuberculosis is itself very rare despite high global prevalence of tuberculosis in developing countries. Majority of thyroid tuberculosis identified in postoperative histopathology or cytopathology. The coexistence of thyroid cancer with tuberculosis or parathyroid adenoma has been reported in the literature but not a single case of the three pathologies coexisting together has been found in the literature published. We are presenting a rare case of a constellation of synchronous parathyroid adenoma, thyroid carcinoma, and thyroid tuberculosis. This case report will provoke researchers to work on understanding the association of hypercalcemia or chronic inflammation leading to development of malignancy or parathyroid adenoma in the presence of hypothyroidism will give future perspective in managing such patients., Case Presentation: A Islam lady aged 45 years old, diagnosed with hypothyroidism, was evaluated for pregnancy loss and rapid weight gain from 13 years back and started on tablets of levothyroxine 25 µg once daily. She was doing well until the past 2 years; there after she noticed insidious onset of a swelling over anterior aspect of right side of the neck and bone pain in back and lower limbs. Patient underwent routine investigations and was found to have raised serum calcium (11.4 mg/dl) and parathyroid hormone (253 pg/ml). Anti-thyroid peroxidase (TPO) and anti-thyroglobulin (Tg) level were normal. Ultrasounds showed multiple nodules in both lobe of thyroid and left inferior parathyroid adenoma. The patient underwent total thyroidectomy with left inferior parathyroidectomy, and final histopathology showed features of subacute granulomatous thyroiditis along with hurthle cell change in right lobe of thyroid. The left lobe additionally showed necrotizing epitheloid cell granulomas, which on Zeihl-Neelson staining revealed presence of acid-fast bacilli. Sections from the isthmus show a focus of papillary thyroid microcarcinoma. The left inferior parathyroid gland sent as a frozen sample was found to be parathyroid adenoma. On 6-month follow-up, the patient was feeling much relief in bone pain and tolerating antitubercular drugs uneventfully., Conclusion: Coexistence of parathyroid adenoma, nonmedullary thyroid carcinoma, and thyroid tuberculosis is extremely rare. Surgery is curative for hyper parathyroidism and thyroid carcinoma. Thyroid tuberculosis responds well to current antitubercular drugs. Its etiology needs to be explored more; the probable hypothesis is chronic inflammation due to latent tuberculosis might leads to development of thyroid carcinoma and parathyroid adenoma. Further studies need to be done for better understanding of underlying mechanism and better management options for such patients. To the best of our knowledge, similar cases have not been reported., (© 2024. The Author(s).)

A deeper understanding of colorectal cancer (CRC) biology would help to identify specific early diagnostic markers. Here, we conducted quantitative proteomics on FFPE healthy, adenoma, and adenocarcinoma tissue samples from six stage I sporadic CRC patients to identify dysregulated proteins during early CRC development. Two independent quantitative 10-plex TMT experiments were separately performed. After protein extraction, trypsin digestion, and labeling, proteins were identified and quantified by using a Q Exactive mass spectrometer. A total of 2681 proteins were identified and quantified after data analysis and bioinformatics with MaxQuant and the R program. Among them, 284 and 280 proteins showed significant upregulation and downregulation (expression ratio ≥1.5 or ≤0.67, p -value ≤0.05), respectively, in adenoma and/or adenocarcinoma compared to healthy tissue. Ten dysregulated proteins were selected to study their role in CRC by WB, IHC, TMA, and ELISA using tissue and plasma samples from CRC patients, individuals with premalignant colorectal lesions (adenomas), and healthy individuals. In vitro loss-of-function cell-based assays and in vivo experiments using three CRC cell lines with different metastatic properties assessed the important roles of SLC8A1 and TXNDC17 in CRC and liver metastasis. Additionally, SLC8A1 and TXNDC17 protein levels in plasma possessed the diagnostic ability of early CRC stages.

Background: The potential of molecular markers in the removed polys as reliable predictors of metachronous lesions is still uncertain., Aim: Our aim was to evaluate the role of somatic mutations in KRAS in polyps of patients with high-risk adenomas to predict the risk of advanced polyps or colorectal cancer (CRC) within 3 years., Methods: A total of 518 patients were prospectively enrolled. The included patients had adenomas ≥10 mm, high-grade dysplasia, villous component or ≥3 more adenomas at baseline and were scheduled to undergo surveillance colonoscopy at 3 years ± 6 months. Somatic KRAS mutation was performed on 1189 polyps collected from these patients. At surveillance, advanced lesions were defined as adenomas with a size of ≥10 mm. High-grade dysplasia or villous component, serrated polyps ≥10 mm or with dysplasia or CRC., Results: At baseline, 81 patients (15.6%) had KRAS mutations in at least one polyp. Patients with KRAS mutated polyps had more frequent villous histological lesions and size ≥20 mm. In the multivariate analysis, adjusted for age and sex, only age (odds ratios [OR], 1.06; 95% confidence interval [CI], 1.02-1.09; p < 0.001), ≥5 adenomas (OR, 3.92; 95% CI, 1.96-7.82), and KRAS mutation (OR, 2.54; 95% CI, 1.48-4.34; p < 0.01) were independently associated with the development of advanced lesions at surveillance., Conclusions: Our results show that, in patients with high-risk adenomas, the presence of somatic mutations in KRAS is an independent risk factor for the development of advanced metachronous polyps., (© 2024 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

The discovery of "mismatch repair deficient (MMRd)-crypt foci" in non-neoplastic intestinal mucosa in Lynch syndrome (LS) has significantly enhanced our understanding of how tumors and tumor immunity form and evolve in LS. In this study, we report the frequent presence of "mismatch repair proficient (MMRp)-crypt foci" in both non-neoplastic and neoplastic intestinal mucosa in a patient with constitutional MMR deficiency (CMMRD), who carried a germline MSH6 pathogenic variant (c.3261dupC) in trans with an MSH6 likely pathogenic variant (c.3724&#95;3726del) and whose tissues were otherwise deficient in MMR globally. The MMRp-crypts occurred at a rate of 1.1/100 crypts in non-neoplastic intestinal mucosa and were readily discernible in adenomas > 1 cm. Sequencing analysis revealed normalization of the MSH6c.3261dupC variant in MMRp-adenoma crypts, indicating reverse frameshifting of the exon 5 C8 microsatellite. Interestingly but not surprisingly, the MMRp-adenoma crypts remained microsatellite-instability-high (MSI-H), and shared oncogenic APC mutations with the background MMRd-adenoma. Contrasting with MSH6-CMMRD, no PMS2-CMMRD individuals (0/5) harbored MMRp-crypts. In conclusion, our study documents distinct MMRp-crypts in MSH6-CMMRD, a phenomenon in keeping with MSH6 being a frequent target of MSI-H due to its coding microsatellite and suggesting that MSH6-CMMRD can potentially serve as a unique model system to further our understanding of MSH6's role in MSI-H tumor formation and evolution. Our findings also bear diagnostic implications; when using MMR immunohistochemistry as an ancillary tool in detecting CMMRD, awareness of these MMRp crypts can help avoid diagnostic pitfalls., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Parathyroid gland (PG) surgery is often challenging due to the small size and indistinct nature of these glands. The introduction of intraoperative near-infrared autofluorescence (NIRAF) has shown promise in localizing parathyroid tissue. However, the NIRAF features of parathyroid adenomas remain unclear. The aim of this study is to assess the NIRAF pattern of parathyroid adenomas., Methods: Patients who underwent surgery for primary hyperparathyroidism at the University Hospital of Pisa, Endocrine Surgery Unit, between December 2021 and February 2022 were enrolled in this study. Intraoperative NIRAF patterns of suspected parathyroid adenomas were evaluated, with particular attention given to the presence of a bright cap., Results: A retrospective study was conducted on 11 patients with primary hyperparathyroidism who underwent parathyroidectomy at our institution. Histopathological examination of the 15 resected specimens confirmed 14 parathyroid adenomas (12 chief cell parathyroid adenomas, 1 oxyphil cell parathyroid adenoma, and 1 mixed cell parathyroid adenoma) and one schwannoma. All adenomas exhibited a heterogeneous NIRAF pattern, distinct from the homogeneous pattern observed in the schwannoma. A bright cap was identified in 9 out of 14 (64.3%) parathyroid adenomas (all chief cell adenomas). On the contrary, all 9 macroscopically normal PGs identified during surgery presented an homogeneous pattern., Conclusion: Our findings support the integration of NIRAF into parathyroid surgical procedures. The heterogeneous NIRAF pattern observed in parathyroid adenomas, often accompanied by a bright cap, offers a promising intraoperative diagnostic tool to differentiate hyperfunctioning from normal parathyroid tissue. Larger-scale randomized trials are warranted to further validate these findings., (© 2024. The Author(s).)

Aberrant expression of cyclin-dependent kinase 5 (Cdk5) has been reported in pituitary adenomas. However, the role of Cdk5 in the tumorigenesis remains unclear. We show that prenatal p25-activated Cdk5 phosphorylates minichromosome maintenance protein 2 (Mcm2), enhancing minichromosome maintenance (MCM) family proteins and driving intermediate lobe-located melanotrope-originated pituitary tumorigenesis. In a mouse model with CaMKII promoter-driven transgenic induction of p25, we observed intermediate lobe-originated pituitary adenoma producing non-functional proopiomelanocortin (POMC)-derived peptides under persistent p25 overexpression. Single-cell RNA sequencing revealed Mcm2 may play an important role during tumor progression. Subsequently, Mcm2 was identified as a potential phosphorylated substrate of Cdk5, mediating the tumorous proliferation of melanotrope cells. Silencing Cdk5 or Mcm2 suppressed cell proliferation and colony formation in the 293T cell lines. Therefore, our findings provide a new mouse model of intermediate lobe-originated pituitary adenoma induced by p25/Cdk5 and unveil a previously unappreciated role of Cdk5 and Mcm2 in pituitary adenoma tumorigenesis., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Importance: The success of parathyroidectomy depends on accurate intraoperative localization and identification of all diseased glands in parathyroid exploration based on surgeon expertise to prevent persistent hyperparathyroidism. Near-infrared autofluorescence (NIRAF) imaging has recently emerged as a promising adjunctive intraoperative tool for localizing parathyroid glands; however, its potential utility in the assessment of parathyroid glands has yet to be established., Objective: To analyze the differences in NIRAF signatures of parathyroid glands in single vs multiple glands in primary hyperparathyroidism (pHPT)., Design, Setting, and Participants: This prospective diagnostic study analyzed in vivo NIRAF images of parathyroid glands obtained during parathyroidectomies between November 18, 2019, and December 31, 2023, at a single tertiary referral center. Pixel intensities of the images were measured using third-party software. Patients who underwent parathyroidectomy for sporadic pHPT using a second-generation NIRAF imaging device were included. Patients with multiple endocrine neoplasm disorders were excluded. In vivo NIRAF images obtained during the procedures were analyzed., Exposure: Near-infrared autofluorescence imaging during parathyroidectomy., Main Outcomes and Measures: The primary outcomes were the autofluorescence intensity and heterogeneity of single adenomas and multigland disease (ie, double adenomas and 3- or 4-gland hyperplasia) in sporadic pHPT. Normalized autofluorescence intensity was calculated by dividing the mean pixel intensity of the parathyroid gland by the background tissue. A heterogeneity index was calculated by dividing the standard deviation by the mean pixel intensity of the gland. The secondary outcome was the visibility of each parathyroid gland on NIRAF imaging before it became apparent to the naked eye during exploration., Results: A total of 1287 in vivo NIRAF images obtained from 377 patients (median [IQR] age, 66 [56-73] years; 299 female [79.3%]) were analyzed. Of all patients, 230 (61.0%) had a single adenoma, 91 (24.1%) had double adenomas, and 56 (14.9%) had 3- or 4-gland hyperplasia. A mean (SD) of 3.4 (1.1) parathyroid glands were identified in the procedures. A comparison of 581 diseased glands (45.1%) and 706 normal glands (54.9%) showed a lower median normalized autofluorescence intensity of 2.09 (95% CI, 1.07-4.01) vs 2.66 (95% CI, 1.43-4.20; effect size = 0.36) and higher heterogeneity index of 0.18 (95% CI, 0.07-0.41) vs 0.11 (95% CI, 0.01-0.27; effect size = 0.45), respectively. Of diseased glands, single adenomas (233 [40.1%]) vs double adenomas (187 [32.2%]) and 3- or 4-gland hyperplasia (161 [27.7%]) had a lower median autofluorescence intensity of 1.92 (95% CI, 1.02-4.44) vs 2.22 (95% CI, 1.10-3.97; effect size = 0.21), respectively. On receiver operating characteristic analysis, the optimal autofluorescence intensity threshold to differentiate between single adenomas vs multigland disease was 2.14, with a sensitivity of 64.4%, specificity of 58.1%, and area under the curve of 0.626., Conclusions and Relevance: These findings suggest that parathyroid glands in single- vs multigland disease may exhibit different autofluorescence characteristics. Although the effect size was modest, the differences identified should be kept in mind when assessing the parathyroid glands during surgical exploration.

Purpose: Sebaceous carcinoma is the third most common nonkeratinocyte skin cancer in the United States with 1,000 cases per year. The clinicopathologic features of sebaceous carcinoma and benign sebaceous neoplasms (adenomas, sebaceomas) can overlap, highlighting the need for molecular biomarkers to improve classification. This study describes the genomic and transcriptomic landscape of sebaceous neoplasms in order to understand tumor etiology and biomarkers relevant for diagnosis and treatment., Experimental Design: We performed whole-genome sequencing (WGS) and whole-transcriptome sequencing (WTS) of sebaceous neoplasms from six academic and two federal healthcare facilities in the United States diagnosed between January 1, 1999, and December 31, 2021., Results: We evaluated 98 sebaceous neoplasms: 64 tumors (32 adenomas, 2 sebaceomas, 5 atypical sebaceous neoplasms, 25 carcinomas) had sufficient material for WGS, 96 tumors (42 adenomas, 11 sebaceomas, 8 atypical sebaceous neoplasms, 35 carcinomas) had sufficient material for WTS, and 62 tumors (31 adenomas, 2 sebaceomas, 5 atypical sebaceous neoplasms, 24 carcinomas) had sufficient material for combined WGS and WTS. Overall, we found decreased cholesterol biosynthesis and increased TP53 mutations, copy number gains (chromosome 6, 8q, and/or 18), and tumor mutation burden-high (>10 mutations/MB) in carcinomas compared to adenomas. Although diminished compared to adenomas, most carcinomas still had higher cholesterol biosynthesis than nonmalignant skin. Multiomics profiling also supported a precancerous model of tumor evolution with sebaceomas and atypical sebaceous neoplasms being likely intermediate lesions., Conclusions: The study findings highlight key diagnostic biomarkers for sebaceous carcinoma and suggest that immunotherapy and modulation of cholesterol biosynthesis could be effective treatment strategies., (©2024 American Association for Cancer Research.)

A 28-year-old female patient developed a 5.5 cm progressive thyroid nodule that was surgically removed due to local symptoms. Histologically, a solitary fibrous tumor (SFT) in a thyroid adenoma was diagnosed. The tumor had a specific NAB2-STAT6 fusion.Solitary fibrous tumors rarely occur in the thyroid gland and are described as both primary and secondary manifestations. The diagnosis, prognosis assessment and treatment decision are carried out analogously to SFT of other localizations., (© 2024. The Author(s).)

Background: Familial adenomatous polyposis (FAP) predisposes individuals to duodenal adenomas. This study describes the histopathological features of endoscopic and surgical specimens from the duodenum, as well as genotype-phenotype associations., Methods: All known FAP patients were included from the Danish Polyposis Register. FAP patients were defined as having more than 100 cumulative colorectal adenomas and/or having a known germline pathogenic variant in the APC gene. Endoscopic procedures, histopathology, and genetics were evaluated., Results: Of 500 FAP patients, 70.6% underwent esophagogastroduodenoscopy (EGD) at least once. Of these, 59.2% presented with detectable duodenal adenomas. The most severe morphology was tubular in 62.7% patients, tubulovillous in 25.4%, and villous in 12.0%, while the most severe dysplasia was low-grade in 67.5% patients, high-grade in 25.4%, and 6.7% had adenocarcinoma. In 6.2% of FAP patients, duodenal resection was recommended, including 29% with duodenal adenocarcinoma. The risk of duodenal surgery was 1.31 per 1,000 person-years (median age: 53 years). The predominant reason for surgery was extensive polyposis (67.7%). Of the patients who underwent duodenal resection, a median of six (IQR: 4-8) EGDs were performed within five years prior to surgery, but 67.6% and 83.9% never underwent a duodenal polypectomy or endoscopic mucosa resection, respectively. Of note, seventeen of 500 patients (3.4%) developed duodenal adenocarcinoma, of which 47% were advanced at diagnosis. Genetic evaluations revealed various pathogenic variants in the APC gene, with no strong genotype-phenotype association., Conclusions: The prevalence of duodenal adenomas and cancer in FAP warrants vigilant endoscopic surveillance. Nevertheless, the need for duodenal surgery persists and should together with endoscopic practice be monitored in national registers., (© 2024. The Author(s).)

Background: Surveillance colonoscopy after polyps have been detected at screening aims to reduce the risk for subsequent colorectal cancer, so-called post-colonoscopy colorectal cancer (PCCRC). Inconsistencies exist as to whether the risk should be stratified by histologic subtype. We aimed to compare the risk for PCCRC mortality in screening participants with sessile serrated lesions (SSLs)/traditional serrated adenomas (TSAs), hyperplastic polyps (HPPs), or conventional adenomas., Methods: Screening colonoscopy registry data were linked to death registry data between 2010 and 2022. We assessed the association of PCCRC death after a diagnosis of SSL/TSA, conventional adenoma, or HPP by Cox regression, and stratified by polyp size ≥10 and <10 mm., Results: 383,801 participants were included in the analysis. There were 1490 HPPs ≥10 mm (2.6%), compared with 1853 SSL/TSAs (19.6%) and 10,960 conventional adenomas (12.9%). When adjusted for polyp location, the association of polyp size ≥10 mm with PCCRC death was of similar magnitude in participants with conventional adenomas (hazard ratio [HR] 3.68, 95%CI 2.49-5.44), SSL/TSAs (HR 2.55, 95%CI 1.13-5.72), and HPPs (HR 5.01, 95%CI 2.45-10.22). Participants with HPPs mostly died of tumors in the distal colon (54.1%; n = 20), while participants with SSL/TSAs more frequently died of proximal tumors (33.3%; n = 3)., Conclusions: Across all histologic types, participants with polyps ≥10 mm had at least a two-fold increase in the likelihood of PCCRC death compared with those with polyps <10 mm. These data suggest that size, rather than histologic subtype, should be a determinant for risk stratification after screening colonoscopy., Competing Interests: M. Trauner has been an advisor for Abbvie, Albireo, BiomX, Boehringer Ingelheim, Falk, Gilead, Genfit, Hightide, Intercept, Jannsen, MSD, Novartis, Phenex, Pliant, Regulus, Siemens, and Shire; has received speaker's fees from BMS, Falk Foundation, Gilead, Intercept, MSD, and Roche; travel grants from AbbVie, Falk Foundation, Gilead, Intercept, Janssen, and Roche; and grants/research support from Albireo, Alnylam, Cymabay, Falk Pharma, Gilead, Intercept, MSD, Madrigal, Takeda, and UltraGenyx. The Medical Universities of Graz and Vienna have filed patents on medical use of norUDCA and M. Trauner is listed as a co-inventor. J. Zessner-Spitzenberg, E. Waldmann, L.-M. Rockenbauer, A. Demschik, D. Penz, and M. Ferlitsch declare that they have no conflict of interest., (Thieme. All rights reserved.)

The existence, composition, and continuity of the medial wall of the cavernous sinus (MWCS) have been extensively studied and debated. However, the precise nature of this membrane remains unknown. Understanding the anatomical characteristics of the MWCS is crucial, notably in relation to pituitary adenomas, which often invade the cavernous sinus. Indeed, surgical treatment of those tumors is frequently incomplete because of such invasion. The anatomical and molecular basis of the peculiar and often lateralized tropism of adenomatous cells to the cavernous sinus is not yet understood and it has been suggested repeatedly that the MWCS is physiologically frail. During the past three decades, there have been several conflicting accounts of the existence, composition, and continuity of this medial wall, but methodological differences and varying definitions could have contributed to the current lack of consensus regarding it. The aim of this systematic review was to summarize previously published data concerning the existence, anatomy, composition, and continuity of the MWCS., (© 2024 American Association of Clinical Anatomists and British Association of Clinical Anatomists.)

Background and Aims: After piecemeal EMR (pEMR) of nonpedunculated colorectal lesions ≥20 mm, guidelines recommend first endoscopic surveillance at 6 months. However, initial surveillance at 12 months may be adequate for selected low-risk lesions and could save the cost, risk, and inconvenience of 1 surveillance examination., Methods: This study retrospectively examined a prospectively collected database of all colorectal lesions referred to our center for endoscopic resection between August 2019 and April 2023. We report recurrence rates of patients with colorectal lesions ≥20 mm removed by pEMR who were assigned to 6-month first surveillance or to 12-month first surveillance (or assigned to a 6-month surveillance visit but did not return until after 10 months)., Results: There were 561 nonpedunculated lesions ≥20 mm that underwent first follow-up, including 490 lesions in 443 patients assigned to 6-month surveillance and 71 lesions in 65 patients assigned to 12-month surveillance. Lesions assigned to 12-month surveillance were smaller (mean size, 25.9 ± 6.1 mm vs 37.0 ± 17.4 mm), more likely serrated (63.4% vs 9.6%), and more often removed by cold pEMR (74.6% vs 20.4%). Twenty-nine lesions in 24 patients assigned to 6-month surveillance presented after 10 months, and their recurrence data were included in the group assigned to 12-month surveillance. Overall recurrence rates at 6 months and 12 months were 10.0% (46 of 461) and 10.0% (10 of 100), respectively. Mean recurrence sizes at 6 and 12 months were 10.9 ± 6.2 mm and 5.0 ± 3.1 mm, respectively. One patient in the 6-month surveillance group had cancer at the pEMR site, but no other recurrences at 6 or 12 months had either cancer or high-grade dysplasia., Conclusions: Twelve-month surveillance seems acceptable for selected colorectal lesions ≥20 mm removed by pEMR. A randomized trial comparing initial 6-month versus 12-month surveillance is warranted for selected lesions., Competing Interests: Disclosure The following authors disclosed financial relationships: D. K. Rex: consultant for Olympus Corporation, Boston Scientific, Braintree Laboratories, Norgine, Medtronic, and Acacia Pharmaceuticals; research support from Olympus Corporation, Medivators, Erbe USA Inc, Braintree Laboratories; and shareholder in Satisfai Health. K. C. Vemulapalli: salaried employee of Cook Research Incorporated, a Cook Group company. J. J. Guardiola: educational and travel support from both Boston Scientific and Olympus Corporation. All other authors disclosed no financial relationships., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

The clinical relevance of the colorectal cancer serrated pathway is evident, but the screening of serrated lesions remains challenging. We aimed to characterize the serum methylome of the serrated pathway and to evaluate circulating cell-free DNA (cfDNA) methylomes as a potential source of biomarkers for the non-invasive detection of serrated lesions. We collected serum samples from individuals with serrated adenocarcinoma (SAC), traditional serrated adenomas, sessile serrated lesions, hyperplastic polyps and individuals with no colorectal findings. First, we quantified cfDNA methylation with the MethylationEPIC array. Then, we compared the methylation profiles with tissue and serum datasets. Finally, we evaluated the utility of serum cfDNA methylation biomarkers. We identified a differential methylation profile able to distinguish high-risk serrated lesions from no serrated neoplasia, showing concordance with tissue methylation from SAC and sessile serrated lesions. Serum methylation profiles are pathway-specific, clearly separating serrated lesions from conventional adenomas. The combination of ninjurin 2 (NINJ2) and glutamate-rich 1 (ERICH1) methylation discriminated high-risk serrated lesions and SAC with 91.4% sensitivity (64.4% specificity), while zinc finger protein 718 (ZNF718) methylation reported 100% sensitivity for the detection of SAC (96% specificity). This is the first study exploring the serum methylome of serrated lesions. Differential methylation of cfDNA can be used for the non-invasive detection of colorectal serrated lesions., (© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Introduction: Pituitary carcinoma (PC) is an extremely rare tumor of the adenohypophysis, which manifests as craniospinal dissemination and/or systemic metastasis. The diagnosis of PC is particularly difficult, as the clinical diagnosis only can be made after the metastasis is found. Owing to the complex diagnostic process and less effective treatments, the clinical prognosis of PC is usually very poor. Hence, it is of great significance to illustrate the diagnosis and treatment course of PC., Methods: In this case report, we described a 48-year-old male patient who was diagnosed with pituitary adenoma (PA) initially and then was diagnosed with PC eventually after spinal cord metastasis was found, and we illustrated the treatment course as well. Furthermore, we summarized all the published case reports until now and provided a comprehensive review of the diagnosis, treatment, prediction, and clinical outcome of PC., Results and Conclusions: We found that most PC patients had adrenocorticotropic hormone/prolactin (ACTH/PRL)-secreting tumors, Ki-67 ≥ 10%, and P53 positivity, which may have the potential to predict the transformation from PA to PC; surgery excision combined with temozolomide (TMZ) and radiotherapy is helpful to prolong the survival of PC patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Liang, Fan, Yang and Cheng.)

Prolactinomas, the most common pituitary-secreting adenomas, can be effectively treated with dopamine D2 receptor (D2R) agonists. However, a subset of them (∼20%) are resistant to dopamine-based therapies and require extirpation. The molecular mechanisms underlying their escape from dopaminergic regulation are not fully elucidated and may include alterations in D2R signaling. D2R can heteromerize with other G protein-coupled receptors, resulting in modulation of dopaminergic signaling. Because the bradykinin receptor type 2 (B2R) is overexpressed in prolactinomas, we interrogated whether this dopaminergic dysregulation observed in some prolactinomas may depend on a physical and functional interaction between D2R and B2R. The formation of B2R-D2R complexes in cultured cells transiently expressing both receptors was validated using NanoBiT technology. Interestingly, although D2R stimulation did not alter B2R-induced intracellular calcium mobilization, B2R stimulation abolished D2R signaling through modulation of cAMP. The existence of B2R-D2R complexes in pituitary adenomas biopsies was evaluated using an ALPHALisa approach. Importantly, B2R-D2R complexes were detected in human prolactinomas and nonfunctioning pituitary adenomas, but not in mixed (prolactin + growth hormone)-secreting adenomas. These results suggest that overexpression of B2R in resistant prolactinomas may promote the formation of B2R-D2R complexes, with B2R precluding D2R signaling, thus generating resistance to D2R agonists., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Background: Canine mammary tumours (CMT) are among the most common types of tumours in female dogs. Diagnosis currently requires invasive tissue biopsies and histological analysis. Tumour cells shed extracellular vesicles (EVs) containing RNAs and proteins with potential for liquid biopsy diagnostics. We aimed to identify CMT subtype-specific proteome profiles by comparing the proteomes of EVs isolated from epithelial cell lines derived from morphologically normal canine mammary tissue, adenomas, and carcinomas., Methods: Whole-cell protein lysates (WCLs) and EV-lysates were obtained from five canine mammary cell lines: MTH53A (non-neoplastic); ZMTH3 (adenoma); MTH52C (simple carcinoma); 1305, DT1406TB (complex carcinoma); and their proteins identified by LC-MS/MS analyses. Gene Ontology analysis was performed on differentially abundant proteins from each group to identify up- and down-regulated biological processes. To establish CMT subtype-specific proteomic profiles, weighted gene correlation network analysis (WGCNA) was carried out., Results: WCL and EVs displayed distinct protein abundance signatures while still showing the same increase in adhesion, migration, and motility-related proteins in carcinoma-derived cell lines, and of RNA processing and RNA splicing factors in the adenoma cell line. WGCNA identified CMT stage-specific co-abundant EV proteins, allowing the identification of adenoma and carcinoma EV signatures not seen in WCLs., Conclusions: EVs from CMT cell lines exhibit distinct protein profiles reflecting malignancy state, allowing us to identify potential biomarkers for canine mammary carcinomas, such as biglycan. Our dataset could therefore potentially serve as a basis for the development of a less invasive clinical diagnostic tool for the characterisation of CMT., (© 2024. The Author(s).)

Background: Duodenal papillary adenoma, a potentially malignant benign tumor is primarily treated with endoscopic papillectomy. Despite its efficacy, endoscopic papillectomy has a high complication rate. This study investigates whether pancreatic duct and common bile duct stent placement can mitigate these complications., Methods: In a retrospective observational analysis, 79 patients with duodenal papillary adenoma, treated with endoscopic papillectomy at our center, were studied. The cohort included patients who underwent endoscopic papillectomy with no stents placement, common bile duct stent placement alone, pancreatic duct stent placement alone, or stents placement in both ducts. We assessed the outcomes of endoscopic papillectomy, including complete resection rate and recurrence rate as the primary and secondary outcomes respectively. In the meantime, the incidence of complications were also analysed as the safety outcomes., Results: Complete resection rates did not significantly differ between patients with or without stent placement (85.7% P group vs. 89.2% N-P group, P = 0.64). Early complication rates were similar across groups. However, significant reduction in common bile duct stenosis was observed in the stenting group (0% B group vs. 10.5% N-B group, P = 0.03). Furthermore, stent placement correlated with lower adenoma recurrence rates during follow-up (2.4% P group vs. 16.2% N-P group, P = 0.03; 2.4% B group vs. 15.8% N-B group, P = 0.04)., Conclusions: Pancreatic duct and common bile duct stent placement in endoscopic papillectomy may decrease late complications, particularly common bile duct stenosis, and reduce the recurrence of duodenal papillary adenoma., Trial Registration: This study received approval from the Institutional Review Board and Ethics Committee of Beijing Friendship Hospital (Approval No. BFHHZS20230203), and retrospectively registered in www., Clinicaltrials: gov (NCT06301048, Initial Release date: 02/18/2024, Last Public Release date: 03/03/2024)., (© 2024. The Author(s).)

Context: The tumor microenvironment (TME) includes diverse cellular components such as mesenchymal stem cells (MSCs) and immune cells, among others. MSC have been isolated from different tumors and they favor tumor cell growth; however, their role in pituitary tumors (PTs) remains unknown., Objective: Herein we report the presence of MSCs in 2 adrenocorticotropin (ACTH)-secreting PTs causing Cushing disease (MCU), 2 nonfunctioning adenomas of gonadotrope differentiation (MNF), and 2 nontumoral pituitary glands (MS)., Methods: We have analyzed the transcriptomic profiles by RNA sequencing and compared MSCs in terms of their immunosuppressive effects against lymphoid T-cell and macrophage populations by means of cocultures and flow cytometry., Results: Our transcriptomic analysis revealed molecular differences between MSCs derived from nontumoral pituitaries and MSCs derived from PTs. Two distinct subpopulations of MSC emerged: one displaying immunosuppressive properties and the other with increased proproliferative capabilities, regardless of their origin. MSCs derived from ACTH- and nonfunctioning PTs, but not those derived from nontumoral glands, significantly inhibited the proliferation of activated T cells, favored the generation of regulatory T cells, and promoted M2 macrophage polarization. Such immunosuppressive effects were correlated with an upregulation of programmed death ligand 1 and intracellular expression of macrophage colony-stimulating factor (M-CSF) and interleukin-10. Importantly, MSC derived from ACTH-PTs showed a higher immunosuppressive potential than MSC isolated from nonfunctioning tumors., Conclusion: This study demonstrates the presence of at least 2 MSC subpopulations in the pituitary gland and suggests that immunosuppressive effects of MSCs may have important implications in PT growth., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Context: CHEK2 is a cell cycle checkpoint regulator gene with a long-established role as a clinically relevant, moderate risk breast cancer predisposition gene, with greater risk ascribed to truncating variants than missense variants., Objective: To assess the rate and pathogenicity of CHEK2 variants amongst individuals with pituitary adenomas (PAs)., Methods: We assessed 165 individuals with PAs for CHEK2 variants. The study population comprised a primary cohort of 29 individuals who underwent germline and tumor whole-exome sequencing, and a second, independent cohort of 136 individuals who had a targeted next-generation sequencing panel performed on both germline and tumor DNA (n = 52) or germline DNA alone (n = 84)., Results: We identified rare, coding, nonsynonymous germline CHEK2 variants amongst 3 of 29 (10.3%) patients in our primary cohort, and in 5 of 165 (3.0%) patients overall, with affected patients having a range of PA types (prolactinoma, thyrotropinoma, somatotropinoma, and nonfunctioning PA). No somatic variants were identified. Two variants were definitive null variants (c.1100delC, c.444 + 1G > A), classified as pathogenic. Two variants were missense variants (p.Asn186His, p.Thr476Met), classified as likely pathogenic. Even when considering the null variants only, the rate of CHEK2 variants was higher in our cohort compared to national control data (1.8% vs 0.5%; P = .049)., Conclusion: This is the first study to suggest a role for the breast cancer predisposition gene, CHEK2, in pituitary tumorigenesis, with pathogenic/likely pathogenic variants found in 3% of patients with PAs. As PAs are relatively common and typically lack classic autosomal dominant family histories, risk alleles-such as these variants found in CHEK2-might be a significant contributor to PA risk in the general population., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Ectopic parathyroid adenoma is a rare pathology. We present a clinical case of a giant ectopic parathyroid adenoma (PA) in an unusual location, which brought significant diagnostical and therapeutical challenges. The tumour in the mediastinum was found incidentally on chest computed tomography (CT). A biopsy was conducted, and histological examination revealed a well-differentiated neuroendocrine tumour. The tumour was excised via right thoracotomy. The final histological examination revealed a parathyroid adenoma, which was unexpected for our team. After three years of observation, there is no evidence of tumour recurrence.

(Background) Cancer-associated fibroblasts (CAFs) are major cancer stromal components. CAFs have diverse functions and cell origins. Podoplanin (PDPN), a lymphatic vessel marker, is also a CAF marker in certain cancers. On daily diagnosis of early colorectal carcinoma (CRC), PDPN upregulation in the stroma is often encountered, suggesting PDPN-positive CAFs have emerged. However, PDPN-positive CAFs in early CRC have not been studied well. (Methods) On immunohistochemistry, PDPN expression in the lamina propria or stroma of adenomas, early CRCs, and neuroendocrine tumors, their normal neighbors, and non-neoplastic colorectal lesions were compared. Single-cell RNA sequencing (scRNA-seq) of CRC was used to explore PDPN high CAFs' cell origins. (Results) Reticular cells or pericryptal fibroblasts in the lamina propria of adenomas and early CRCs showed higher PDPN expression than did normal mucosae and non-neoplastic lesions ( p < 0.01). Pericryptal PDPN expression was a diagnostic feature of adenomas and early CRCs. scRNA-seq of CRCs highlighted that PDPN high CAFs had distinctly higher COL4A1 , COL4A2 , and WNT5A expression, unlike well-known CAFs characterized by high FAP, POSTN , or ACTA2 expression. (Conclusions) We demonstrated that pericryptal fibroblasts and reticular cells in the lamina propria are origins of early-stage CRC CAFs and thus have potential as a diagnostic marker for distinguishing colorectal non-neoplastic from neoplastic lesions.

Introduction: Pituitary adenomas (PAs) are benign tumors with high prevalence and, occasionally, aggressive course. The tumorigenesis of these lesions is not completely understood at the molecular level. BAK1 and BAX proteins play fundamental roles in apoptosis and seem to interact with VDAC proteins, whose expressions have been markedly altered in cancer, impacting their prognosis., Objective: to evaluate the gene expression of VDAC1, VDAC2, BAK1 and BAX and their association with clinical and imaging characteristics in PA., Methods: Clinical-epidemiological data were collected from 117 tumor samples from patients affected by PA. Invasiveness was assessed by the Knosp scale. Gene expression was examined by real-time PCR. Relative expression analysis was performed by 2^(-DDCt) method., Results: The sample was mainly composed of women (69/117 - 57.2%). Tumor subtypes observed were Non-Functioning (NF) (73/117 - 62.4%), Acromegaly (24/117 - 20.5%) and Cushing's Disease (CD) (20/117 - 17.1%). Compared to normal tissue, there was a significant reduction in VDAC1 expression in the Acromegaly (p=0.029) and NF (p=0.002) groups. BAX expression was lower in all groups (p <0.001; p=0.007; P =0.005). No difference was found in VDAC2 and BAK1 expression, compared to normal pituitary. Overexpression of VDAC2 occurred in PAs with post-surgical regrowth (p=0.042). A strongly negative correlation was observed in BAX and BAK1 expression in CD., Conclusion: The results indicated that downregulations of VDAC1 and BAX may be related to resistance to apoptosis. In contrast, overexpression of VDAC2 in regrowing PAs suggests an antiapoptotic role for this gene. In summary, the genes evaluated might be involved in the biopathology of PAs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Facundo, Magalhães, Nascimento, Azulay, Santos, Freitas, Nascimento, Rodrigues, Santos, Beckman, Abreu, Silva, Carneiro, Oliveira Neto, Gil da Costa, Corcoy, Mato and Faria.)

Pituitary adenomas that extend to the ventricular system are extremely rare. We present a 5-year natural history of a giant null cell pituitary adenoma with invasion into the cavernous sinus extending to the third ventricle. MRI series that were available could be useful for neurosurgeons, ophthalmologists, and endocrinologists as well as radiologists. Patients with the diagnosis of pituitary adenoma that are certain according to the radiological and clinical examination should be consulted by a neurosurgeon experienced in endoscopic endonasal surgery, a neuroendocrinologist, and an ophthalmologist. The surgery postponement in such cases results in disability and quality of life worsening. At that time, the surgery of giant pituitary adenomas demands high skills, and the risk of postoperative complications is high. The proper treatment modality including earlier surgery seems to be favorable for patient outcome.

Primary hyperparathyroidism (PHPT) due to ectopic parathyroid adenoma is a rare case of hypercalcemia in the pediatric population. Herein, a rare case of PHPT due to ectopic intrathymic parathyroid adenoma was described in an asymptomatic 15-year-old girl who had incidental diagnosis based on laboratory abnormalities but experienced a 3-month postoperative course of persistently elevated parathyroid hormone (PTH) and hypercalcemia following the initial unsuccessful parathyroidectomy operation carried out in a non-parathyroid expert center. The curative surgical treatment was accomplished only after the patient was reoperated with video-assisted thoracoscopic surgery (VATS) thymectomy by the surgeon experienced in parathyroid surgery with implementation of the combined imaging modalities for accurate localization of ectopic adenoma including 99mTc sestamibi (MIBI) plus neck and thoracic computed tomography (CT) and the appropriate surgical strategies including intraoperative intact PTH monitoring and frozen section diagnosis. Before the reoperation (VATS thymectomy), laboratory findings showed elevated PTH (1,171 ng/L; reference range: 21.80 ng/L-87.5 ng/L) and hypercalcemia (13.4 mg/dL; reference range: 8.4 mg/dL-10.2 mg/dL). The preoperative PTH levels were 94 ng/L at 5 min after thymectomy and 78 ng/L at 10 min. The PTH and calcium levels were 54.3 ng/L and 8.47 mg/dL, respectively, on postoperative day 1 and were 34.2 ng/L and 8.1 mg/dL on postoperative day 2. The patient was discharged on postoperative day 2 without any complications. In conclusion, our findings indicate the likelihood of isolated primary hyperparathyroidism to be incidentally diagnosed based solely on laboratory abnormalities with no specific clinical manifestations in the pediatric age. In addition, using combined imaging modalities (such as MIBI and CT) in accurate localization of ectopic parathyroid adenoma and implementation of surgery by experienced surgeons along with intraoperative intact PTH monitoring and frozen section diagnosis seem crucial to ensure the curative surgical treatment., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gurluler.)

Introduction: Historically, Multiple Endocrine Neoplasia type 1 (MEN1)-related pituitary adenomas (PAs) were considered more aggressive and treatment-resistant than sporadic PAs. However, recent studies suggest similarities in their behavior. This study aimed to evaluate the long-term outcomes of MEN1 PAs and identify predictive factors., Methods: Nationwide multicenter retrospective cohort study of MEN1-related PAs with a minimum 1-year follow-up, collecting patient demographics, germline MEN1 pathogenic variants (PV), PA size, secretory profile, radiological characteristics, treatments, and outcomes., Results: We analyzed 84 PAs, 69%in females and 31% in males (P<0.001), diagnosed at a mean age of 35.2±14.9 years, mostly through screening (60.7%). Median follow-up was 9 years (IQR:4-16). Prolactin-secreting PAs (PRLomas) (53.5%) and microadenomas (65.5%) were most common. Dopamine agonist treatment was first line for 16 macroPRLomas and 25 microPRLomas, 60.9% of them achieved PRL normalization. There was no significant association observed with tumor size, sex, treatment duration or MEN1 PV. The risk of progression from micro-PA to invasive macro-PA was 7.2% (4/55), after 8 years (IQR:4-13), all of them were microPRLomas. Kaplan-Meier estimation curve showed significantly higher progression probability in microPRLomas than in other microadenomas subtypes (P=0.017) or microNFPAs (P=0.032). No differences were found between sex, age, or germline MEN1 PV., Conclusion: MEN1-related micro-PAs have a low risk of progressing to invasive macro-PAs, regardless of sex, age at diagnosis, or MEN1 germline PV. The risk is higher for microPRLomas over the long term. Therefore, long-term surveillance with reduced frequency, rather than intensive short-term monitoring, may be appropriate for patients with MEN1-related PAs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Valdés, Romero, Diego, Calatayud, Lamas, Araujo-Castro, Álvarez-Escolá, Díaz, Alcázar, Sastre, Martínez, Oriola, Paja, Sánchez-Sobrino, Salinas, Recio-Córdova, Navarro, Chiara, Castaño and Casterás.)

Dysregulated fatty acid metabolism is an attractive therapeutic target for colorectal cancer (CRC). We previously reported that fatty acid synthase (FASN), a key enzyme of de novo synthesis, promotes the initiation and progression of CRC. However, the mechanisms of how upregulation of FASN promotes the initiation and progression of CRC are not completely understood. Here, using Apc /VillinCre and Apc Min mouse models, we show that upregulation of FASN is associated with an increase in activity of β-catenin and expression of multiple stem cell markers, including Notum. Genetic and pharmacological downregulation of FASN in mouse adenoma organoids decreases the activation of β-catenin and expression of Notum and significantly inhibits organoid formation and growth. Consistently, we demonstrate that NOTUM is highly expressed in human CRC and its expression positively correlates with the expression of FASN in tumor tissues. Utilizing overexpression and shRNA-mediated knockdown of FASN, we demonstrate that upregulation of FASN increases β-catenin transcriptional activity, NOTUM expression and secretion, and enhances stem-like properties of human CRC cells. Pharmacological inhibition of NOTUM decreases adenoma organoids growth and proliferation of cancer cells. In summary, upregulation of FASN enhances β-catenin signaling, increases NOTUM expression and stem-like properties of CRC cells, thus suggesting that targeting FASN upstream of the β-catenin/NOTUM axis may be an effective preventative therapeutic strategy for CRC.

The expression of several key molecules is altered in parathyroid tumors due to gene mutations, the loss of heterozygosity, and aberrant gene promoter methylation. A set of genes involved in parathyroid tumorigenesis has been investigated in sporadic parathyroid adenomas (PAds). Thirty-two fresh PAd tissue samples surgically removed from patients with primary hyperparathyroidism (PHPT) were collected and profiled for gene, microRNA, and lncRNA expression (n = 27). Based on a gene set including MEN1 , CDC73 , GCM2 , CASR , VDR , CCND1 , and CDKN1B , the transcriptomic profiles were analyzed using a cluster analysis. The expression levels of CDC73 and CDKN1B were the main drivers for clusterization. The samples were separated into two main clusters, C1 and C2, with the latter including two subgroups of five PAds (C2A) and nineteen PAds (C2B), both differing from C1 in terms of their lower expression of CDC73 and CDKN1B . The C2A PAd profile was also associated with the loss of TP73, an increased expression of HAR1B , HOXA-AS2 , and HOXA-AS3 lncRNAs, and a trend towards more severe PHPT compared to C1 and C2B PAds. C2B PAds were characterized by a general downregulated gene expression. Moreover, CCND1 levels were also reduced as well as the expression of the lncRNAs NEAT1 and VLDLR-AS1 . Of note, the deregulated lncRNAs are predicted to interact with the histones H3K4 and H3K27. Patients harboring C2B PAds had lower ionized and total serum calcium levels, lower PTH levels, and smaller tumor sizes than patients harboring C2A PAds. In conclusion, PAds display heterogeneous transcriptomic profiles which may contribute to the modulation of clinical and biochemical features. The general downregulated gene expression, characterizing a subgroup of PAds, suggests the tumor cells behave as quiescent resting cells, while the severity of PHPT may be associated with the loss of p73 and the lncRNA-mediated deregulation of histones.

Background: While statistically rare in comparison to other head and neck tumours, parotid gland swellings are often encountered in clinical practice where one of the primary goals of examination becomes distinction between benign and malignant lesions. Hallmarks of malignancy are characterized by a female preponderance, history of radiation exposure, a positive family history, and clinical features like heterogenous consistency, fixity to skin/underlying tissues and involvement of facial nerve., Case Presentation: Here we present a case of parotid swelling in a 72-year old gentleman from south India that had a curious amalgamation of both benign and malignant features., Conclusions: While benign, the risk of malignant transformation and rare multicentric occurrence indicates a need to keep basal cell adenoma in mind in case of parotid swellings and their surgical management., (© 2024. The Author(s).)

Background: Pituitary adenomas (PAs) are the second most common intracranial tumor. While current diagnostic practices rely primarily on histological testing, they often fail to capture the molecular complexities of pituitary adenomas, underscoring the need for a molecular-based classification to refine therapeutic strategies and prognostic assessments. This study aims to provide a molecularly unbiased classification of pituitary adenomas and explore their unique gene expression patterns and clinical features., Methods: We performed unsupervised hierarchical clustering of the gene expression profiles of 117 PA samples to identify three distinct molecular subtypes. Subsequently, we analyzed the compiled transcriptomic profiles of each individual subtype for pathway enrichment. We also validated the new classification with a validation set containing 158 PAs and 24 pituitary adenoma stem cells (PASCs)., Results: Consensus clustering of transcriptomic data from 117 pituitary adenoma (PA) samples identified three distinct molecular subtypes, each showing unique gene expression patterns and associated biological processes: Group I is enriched in signaling pathways, such as the cAMP signaling pathway and the calcium signaling pathway. Group II is primarily related to metabolic processes, including nitrogen metabolism and arginine biosynthesis in cancer. Group III predominantly shows enrichment in immune responses and potential malignant transformation of the disease, especially through cancer-related pathways such as the JAK-STAT signaling pathway and the PI3K-Akt signaling pathway. The immune profiling revealed distinct patterns for each subtype: Group I had higher dendritic cells and fewer CD8+ T cells, Group II had more monocytes and macrophages, and Group III had elevated levels of T cells. Additionally, there were differences in clinical characteristics and prognosis among the subtypes, with Group III having a worse prognosis, despite the smaller tumor size compared to other groups. Notably, differences in PASCs correlated with the molecular subtypes, with Group III stem cells being enriched in tumorigenesis pathways, PI3K-Akt signaling pathway and Ras signaling pathway., Conclusion: Our study introduces a novel molecular classification for pituitary adenomas, independent of traditional histological methods. Each subtype features distinct genetic, molecular, and immunological profiles. We have isolated pituitary adenoma stem-like cells (PASCs), pairing them with tumor tissues for detailed transcriptomic analysis. These PASCs exhibit diverse molecular traits consistent with the new classification., (© 2024. The Author(s).)

Background: Colorectal cancer is the 4th most reported reason for cancer death worldwide. It is a complex and multifaceted disease with diverse histopathological manifestations. CD70 is present on activated immune cells and is upregulated in patients who have finished adjuvant therapy. VEGF controls angiogenesis and demonstrates immuno-regulatory characteristics that inhibit the anticancer activity of immune cells. CD90 is an extracellular cancer stem cell marker and regulates apoptosis, cell migration, and T cell activation., Aim of Work: to elucidate the prognostic potential of a combined immunohistochemical assessment of CD70, VEGF, and CD90 biomarkers in colorectal cancer tissues., Materials and Methods: Our study is a retrospective study done on 70 paraffin blocks (45 colorectal carcinoma cases and 11 adenomas, along with 14 cases of colitis serving as controls) were subjected to conventional Hematoxylin and Eosin stain for routine histopathological assessment and immunohistochemical staining for CD70, VEGF and CD90. Our investigation focused on evaluating the expression of CD70, VEGF, and CD90 in various colorectal tissues, including colitis, adenomas, and adenocarcinomas, as well as different grades of adenocarcinoma tissues, different stages of tumor invasiveness, and lymph node status., Results: Our research revealed distinctive expression patterns of CD70, VEGF, and CD90 across different stages and grades of colorectal cancer., Conclusion: our research signifies the potential clinical utility of the CD70, VEGF, and CD90 triad as prognostic markers in colorectal cancer. The combined analysis of these markers emerged as a potent prognostic tool, offering valuable insights into disease progression. Our research showed that epithelial CD90 is the most sensitive marker for both tumor stage and lymph node status. CD70 and VEGF showed a statistically significant relation with lymph node status only and not with tumor stage.

Temporal ordering of cellular events offers fundamental insights into biological phenomena. Although this is traditionally achieved through continuous direct observations 1,2 , an alternative solution leverages irreversible genetic changes, such as naturally occurring mutations, to create indelible marks that enables retrospective temporal ordering 3-5 . Using a multipurpose, single-cell CRISPR platform, we developed a molecular clock approach to record the timing of cellular events and clonality in vivo, with incorporation of cell state and lineage information. Using this approach, we uncovered precise timing of tissue-specific cell expansion during mouse embryonic development, unconventional developmental relationships between cell types and new epithelial progenitor states by their unique genetic histories. Analysis of mouse adenomas, coupled to multiomic and single-cell profiling of human precancers, with clonal analysis of 418 human polyps, demonstrated the occurrence of polyclonal initiation in 15-30% of colonic precancers, showing their origins from multiple normal founders. Our study presents a multimodal framework that lays the foundation for in vivo recording, integrating synthetic or natural indelible genetic changes with single-cell analyses, to explore the origins and timing of development and tumorigenesis in mammalian systems., (© 2024. The Author(s).)

Pituitary adenomas (PAs) are an array of tumors originating from the pituitary gland. PAs are sorted as functional or nonfunctional according to their hormonal activity and classified according to size into microadenomas and macroadenomas. Still, the cellular events that trigger the transformations in pituitary neoplasms are not fully understood, and the current classification methods do not precisely predict clinical behavior. A rising number of researches have emphasized the role of miRNAs, that drawn more attention as oncogenic molecules or tumor suppressors. The etiopathological mechanisms of PAs include multiple molecular cascades that are influenced by different miRNAs. miRNAs control the cell cycle control, pro- or antiapoptotic processes, and tumor invasion and metastasis. miRNAs offer a novel perspective on tumor features and behaviors and might be valuable in prognostication and therapeutic plans. In pituitary adenomas, miRNAs showed a specific expression pattern depending on their size, cell origin, remission, and treatments. Screening miRNA expression patterns is promising to monitor and evaluate recurrence, as well as to investigate the efficacy of radiation and chemotherapy for PAs exhibiting aggressive behavior. Thus, the current review investigated the interplay of the miRNAs' pivotal role in offering new opportunities to translate these innovative epigenetic tools into healthcare applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Oxyntic gland neoplasm (OGN) is a rare condition that can be classified as oxyntic gland adenoma (OGA) or gastric adenocarcinoma of fundic-gland type (GA-FG). GA-FG primarily presents as early gastric cancer, with only a few reported cases of advanced gastric cancer (AGC). We aimed to investigate the clinicopathological features of OGN and describe an aggressive variant., Materials and Methods: We investigated a total of 29 cases, including a patient with double primary cases, diagnosed with OGN or differentiated-type adenocarcinoma with GA-FG morphology, between November 2016 and April 2022. We analyzed 54 pathological specimens and reviewed their clinicopathological, endoscopic, and histological features. The lesions were reclassified as OGA or GA-FG, and immunohistochemical (IHC) staining for MUC-5AC and MUC-6 was performed on available resected GA-FG cases., Results: The median patient age was 65 years and males accounted for 58.6% of patients. Most cases occurred in the body horizontally (69.0%) and on the greater curvature side cross-sectionally (48.3%). Endoscopically, type 0-IIa (41.4%) and a subepithelial tumor-like appearance (24.1%) were the most common findings. Histologically, there were 8 cases of OGA (27.6%) and 21 cases of GA-FG (72.4%). In GA-FG, MUC-6 was positive in 13 cases (81.3%), whereas MUC-5AC was positive in 8 cases (50.0%). Three cases presented as AGCs., Conclusions: Although OGNs are generally considered low-grade, they can present as AGCs and may exhibit features of lymphovascular or perineural invasion. Recognizing the clinicopathological features and accurately diagnosing OGN are important for providing adequate treatment., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2024. Korean Gastric Cancer Association.)

Background: Complete endoscopic resection of superficial non-ampullary duodenal epithelial tumors (SNADETs) is technically difficult, especially with an extremely high risk of adverse event (AE), although various endoscopic resection methods including endoscopic mucosal resection (EMR), underwater EMR (UEMR), and endoscopic submucosal dissection (ESD) have been tried for SNADETs. Accordingly, a novel simple resection method that can completely resect tumors with a low risk of AEs should be developed., Aims: A resection method of Noninjecting Resection using Bipolar Soft coagulation mode (NIRBS) which has been reported to be effective and safe for colorectal lesions is adapted for SNADETs. In this study we evaluated its effectiveness, safety, and simplicity for SNADETs measuring ≤ 20 mm., Results: This study included 13 patients with resected lesions with a mean size of 7.8 (range: 3-15) mm. The pathological distributions of the lesions were as follows: adenomas, 77% (n = 10) and benign and non-adenomatous lesions, 23% (n = 3). The en bloc and R0 resection rate was 100% (n = 13). The median procedure duration was 68 s (32-105). None of the patients presented with major AEs including bleeding and perforation., Conclusions: Large studies such as prospective, randomized, and controlled trials should be conducted for the purpose of validating effectiveness, safety, and simplicity of the NIRBS for SNADETs measuring ≤ 20 mm suggested in this study., (© 2024. The Author(s).)