Diagnostic application of the ColonFlag AI tool in combination with faecal immunochemical test in patients on an urgent lower gastrointestinal cancer pathway.

OBJECTIVE: Colorectal cancer (CRC) is the fourth most common cancer in the UK. Patients with symptoms suggestive of CRC should be referred for urgent investigation. However, gastrointestinal symptoms are often non-specific and there is a need for suitable triage tools to enable prioritisation of investigations. In this study, the performance of the faecal immunochemical test (FIT), anaemia and the artificial intelligence algorithm ColonFlag were retrospectively examined and evaluated for their potential clinical benefits in patients who had been referred on an urgent lower gastrointestinal cancer pathway. DESIGN: All patients aged over 40 years referred in a 12-month period were included. After 6 months, clinical outcomes were determined and the performance of the triage tests was evaluated. RESULTS: A total of 3822 patients completed investigations and received a diagnosis. 143 had CRC, 126 high-risk adenomas (HRA). ColonFlag would have missed 27 CRC and 29 HRA. Faecal haemoglobin (f-Hb) at a cut-off of 10 µg/g would have missed 10 CRC and 26 HRA; f-Hb in combination with anaemia would have missed 2 CRC and 14 HRA. Using f-Hb in combination with ColonFlag would have missed only 1 CRC and 5 HRA and would have reduced the need for urgent referral by over 400 patients. CONCLUSION: ColonFlag has potential to assist detection of CRC and HRA, alone where no faecal sample is present and in combination with FIT and to reduce the need for urgent referral.

Phenotypic presentation of MEN1 c.758delC (p.Ser253Cysfs *28) pathogenic variant: a case report.

MEN1 is a rare syndrome caused by mutations in the MEN1 gene. We describe a clinical case of MEN1 syndrome associated with a recently discovered pathogenic mutation of MEN1 gene. A 32-year-old man with a history of osteopenia, nephrolithiasis, hypercalcemia and hypophosphatemia, impaired fasting glucose, and asthenia was admitted to our outpatient unit. Primary hyperparathyroidism, sustained by three hyperplastic parathyroid glands, was diagnosed. Prolactin- and GH-secreting adenomas were ruled out. After undergoing subtotal parathyroidectomy, the patient was diagnosed with non-functioning pituitary adenoma, three pancreatic lesions, and Cushing syndrome sustained by left adrenal adenoma. The patient underwent left adrenal surgery; somatostatin analogue lanreotide was started for the pancreatic lesions; the pituitary adenoma, being small and non-secreting, was not treated. A genetic test was performed to confirm the diagnosis of MEN1 syndrome, finding an association with a recently discovered mutation: the (NM_130799.2):c.758delC (p.Ser253Cysfs*28) in exon 4.

Microbiota-induced S100A11-RAGE axis underlies immune evasion in right-sided colon adenomas and is a therapeutic target to boost anti-PD1 efficacy.

BACKGROUND: Tumourigenesis in right-sided and left-sided colons demonstrated distinct features. OBJECTIVE: We aimed to characterise the differences between the left-sided and right-sided adenomas (ADs) representing the early stage of colonic tumourigenesis. DESIGN: Single-cell and spatial transcriptomic datasets were analysed to reveal alterations between right-sided and left-sided colon ADs. Cells, animal experiments and clinical specimens were used to verify the results. RESULTS: Single-cell analysis revealed that in right-sided ADs, there was a significant reduction of goblet cells, and these goblet cells were dysfunctional with attenuated mucin biosynthesis and defective antigen presentation. An impairment of the mucus barrier led to biofilm formation in crypts and subsequent bacteria invasion into right-sided ADs. The regions spatially surrounding the crypts with biofilm occupation underwent an inflammatory response by lipopolysaccharide (LPS) and an apoptosis process, as revealed by spatial transcriptomics. A distinct S100A11+ epithelial cell population in the right-sided ADs was identified, and its expression level was induced by bacterial LPS and peptidoglycan. S100A11 expression facilitated tumour growth in syngeneic immunocompetent mice with increased myeloid-derived suppressor cells (MDSC) but reduced cytotoxic CD8+ T cells. Targeting S100A11 with well-tolerated antagonists of its receptor for advanced glycation end product (RAGE) (Azeliragon) significantly impaired tumour growth and MDSC infiltration, thereby boosting the efficacy of anti-programmed cell death protein 1 therapy in colon cancer. CONCLUSION: Our findings unravelled that dysfunctional goblet cells and consequential bacterial translocation activated the S100A11-RAGE axis in right-sided colon ADs, which recruits MDSCs to promote immune evasion. Targeting this axis by Azeliragon improves the efficacy of immunotherapy in colon cancer.

Lymphovascular invasion is a dominant risk factor for lymph node metastasis in T2 rectal cancer.

Background and study aims Surgical resection is standard treatment of T2 rectal cancer due to risk of concomitant lymph node metastases (LNM). Local resection could potentially be an alternative to surgical treatment in a subgroup of patients with low risk of LNM. The aim of this study was to identify clinical and histopathological risk factors of LNM in T2 rectal cancer. Patients and methods This was a retrospective registry-based population study on prospectively collected data on all patients with T2 rectal cancer undergoing surgical resection in Sweden between 2009 and 2021. Potential risk factors of LNM, including age, gender, resection margin, lymphovascular invasion (LVI), histologic grade, mucinous cancer, and perineural invasion (PNI) were analyzed using univariate and multivariate logistic regression. Results Of 1607 patients, 343 (21%) with T2 rectal cancer had LNM. LVI (odds ratio [OR] = 4.21, P < 0.001) and age < 60 years (OR = 1.80, P < 0.001) were significant and independent risk factors. However, PNI (OR = 1.50, P = 0.15), mucinous cancer (OR = 1.14, P = 0.60), histologic grade (OR = 1.47, P = 0.07) and non-radical resection margin (OR = 1.64, P = 0.38) were not significant risk factors for LNM in multivariate analyses. The incidence of LNM was 15% in the absence of any risk factor. Conclusions This was a large study on LNM in T2 rectal cancer which showed that LVI is the dominant risk factor. Moreover, low age constituted an independent risk factor, whereas gender, resection margin, PNI, histologic grade, and mucinous cancer were not independent risk factors of LNM. Thus, these findings may provide a useful basis for management of patients after local resection of early rectal cancer.

Expression assays of selected lncRNAs in non-functioning pituitary adenomas.

PURPOSE: Non-functioning pituitary adenomas (NFPAs) are a group of these neoplasms originated from the adenohypophyse and do not show evidence of hormonal oversecretion. However, different genes and lncRNAs have been found to be dysregulated in these samples. MATERIAL AND METHODS: In this study, in order to identify novel biomarkers, a set of regulatory lncRNAs for the two important hub genes, i.e. STAT3 and EGFR were selected and subjected to experimental investigation. These lncRNAs were EGFR-AS1 for the EGFR gene, and LINC00240, FALEC and SNHG12 for the STAT3 gene. RESULTS: All studied genes were down-regulated in NFPA samples compared with normal tissues adjacent to the tumors (NTATs), except for FALEC whose expression was not different between these two sets of samples. EGFR was the most significantly down-regulated gene in NFPAs (Expression ratio (95% CI) = 0.009 (0.002-0.04), P value < 0.0001). ROC curve analyses proposed that the expression levels of SNHG12, EGFR, EGFR-AS1 and LINC00240 can be used to distinguish NFPAs from NTATs with AUC values of 0.88, 0.83, 0.7 and 0.66, respectively. Spearman's correlation analyses showed significant correlations between FALEC and EGFR-AS1 in both types of tissues, and between FALEC and EGFR in NFPAs. Moreover, expression of LINC00240 was correlated with EGFR-AS1, FALEC and SNHG12 in NFPAs. CONCLUSION: Taken together, EGFR and STAT3-related lncRNAs may be involved in the pathogenesis of NFPA.

Innovative imaging approaches for neuroendocrine tumor characterization: Combined dual energy CT and perfusion protocol implementation.

The article addresses the diagnostic value of the combined use of computed tomography (CT) perfusion and dual-energy CT (DECT) in patients with neuroendocrine tumors. It emphasizes the heterogeneity and complexity of these neoplasms, primarily affecting the gastrointestinal tract, bronchopulmonary system, and pancreas. While conventional CT is widely employed in their diagnosis, the combination of CT perfusion and dual-energy CT offers greater precision, particularly in detecting synchronous tumors and characterizing their vascularization. A clinical case of a patient with chronic abdominal symptoms, whose diagnosis was facilitated using both combined techniques, is presented. The discussion explores how CT perfusion assesses tumor vascularization and how dual-energy CT improves soft tissue differentiation, resulting in increased diagnostic accuracy. It is highlighted that this approach not only enhances detection rates but also positively impacts clinical management and healthcare costs. Therefore, the importance of considering these advanced tools in the diagnosis of neuroendocrine tumors to improve diagnostic precision and efficiency in patient care is underscored.

Exosomal AFAP1-AS1 Promotes the Growth, Metastasis, and Glycolysis of Pituitary Adenoma by Inhibiting HuR Degradation.

Exosomal long noncoding RNAs (lncRNAs), which are highly expressed in tumor-derived exosomes, regulate various cellular behaviors such as cell proliferation, metastasis, and glycolysis by facilitating intercellular communication. Here, we explored the role and regulatory mechanism of tumor-derived exosomal lncRNAs in pituitary adenomas (PA). We isolated exosomes from PA cells, and performed in vitro and in vivo assays to examine their effect on the proliferation, metastasis, and glycolysis of PA cells. In addition, we conducted RNA pull-down, RNA immunoprecipitation, co-immunoprecipitation, and ubiquitination assays to investigate the downstream mechanism of exosomal AFAP1-AS1. Exosomes from PA cells augmented the proliferation, mobility, and glycolysis of PA cells. Moreover, AFAP1-AS1 was significantly enriched in these exosomes and stimulated the growth, migration, invasion, and glycolysis of PA cells in vitro, as well as tumor metastasis in vivo. It also enhanced the binding affinity between Hu antigen R (HuR) and SMAD-specific E3 ubiquitin protein ligase 1 (SMURF1), resulting in HuR ubiquitination and degradation accompanied by enhanced expression of hexokinase 2 (HK2) and pyruvate kinase M2 (PKM2). Moreover, HuR overexpression alleviated the exosomal AFAP1-AS1-mediated promotion of growth, metastasis, and glycolysis effects. These findings indicate that tumor-derived exosomal AFAP1-AS1 modulated SMURF1-mediated HuR ubiquitination and degradation to upregulate HK2 and PKM2 expression, thereby enhancing PA cell growth, metastasis, and glucose metabolism. This suggests targeting exosomal AFAP1-AS1 may be a potential strategy for the treatment of PA.

"Intrasellar tumor-to-tumor metastasis: A single center experience with a systematic review".

PURPOSE: This study investigates the rare occurrence of tumor-to-tumor metastasis in Pituitary Neuroendocrine Tumors (PitNETs), also known as pituitary adenomas, aiming to enhance understanding of its diagnostic and therapeutic challenges. We report two cases from our institution of tumor-to-tumor metastasis involving PitNETs, followed by a systematic literature review. METHODS: We conducted a comprehensive literature review using PubMed and Google Scholar databases. This review provides insights into patient demographics, clinical presentations, primary tumor origin, management approaches and outcomes. RESULTS: We identified 38 documented cases of tumor-to-tumor metastasis involving the pituitary gland in the literature. This revealed a diverse range of primary tumor origins, with lung, breast, and renal carcinomas being the most prevalent. Clinical presentations varied, with visual disturbances emerging as the most frequently reported symptom. Surgical interventions predominantly resulted in subtotal resection. Kaplan-Meier survival analysis demonstrated that endoscopic endonasal approaches (EEA) are associated with longer median survival times compared to other surgical methods. CONCLUSION: Tumor-to-tumor metastasis to PitNETs must be considered in differential diagnoses of sellar masses. Prompt and accurate diagnosis, coupled with a multidisciplinary treatment strategy, is essential. Our study contributes to the scarce literature on such metastases, providing a foundation for further understanding of this complex pathological entity.

Both Th1 and Th2 CD4 + T-Cell Lineage Infiltrations Decrease in Post-hematopoietic Stem Cell Transplantation Colon Adenoma.

PURPOSE: As long-term survival improves after allogeneic hematopoietic stem cell transplantation (HSCT), the risk for secondary solid cancers, including colon cancer, also increases. However, the pathogenesis of secondary solid cancers in post-HSCT patients remains unclear. This study aimed to investigate the involvement of local immunity in colon carcinogenesis in post-HSCT patients by assessing the infiltrating T cells in colon adenomas as premalignant lesions of colon cancer in adenoma-carcinoma sequence. METHODS: Colon adenoma samples obtained from 19 post-HSCT patients and 57 non-HSCT participants were analyzed via immunohistochemistry. Double staining of CD4/T-bet, CD4/GATA3, and CD4/FoxP3 was performed for evaluation of helper T-cell lineages (Th1, Th2, and regulatory T cells, respectively) and CD8 staining for CD8+ T cells. RESULTS: There were no significant between-group differences in the number of infiltrating CD4+ T cells and CD8+ T cells in adenomas. However, the number of both CD4+/T-bet+ and CD4+/GATA3+ T cells was significantly lower in the post-HSCT adenomas than in the non-HSCT adenomas (P = 0.0171 and 0.0009, respectively), whereas no significant differences were found in the number of CD4+/FoxP3+ cells. CONCLUSION: Although the number of infiltrating CD4+ and CD8+ T cells, and even Treg cell counts, is sufficiently recovered post-HSCT, CD4+ T-cell dysfunction due to suppressed activation and differentiation in colon adenomas might be involved in colon carcinogenesis in post-HSCT patients. Elucidating the pathogenesis will contribute to the development of effective screening and prevention programs for secondary colon cancer in post-HSCT patients.

The nomogram for predicting nasal bleeding after endoscopic transsphenoidal resection of pituitary adenomas: a retrospective study.

Objective: This study aimed to develop and validate a dynamic nomogram to assess the risk of nasal bleeding after endoscopic transnasal transsphenoidal pituitary tumor resection. Methods: A retrospective analysis was conducted on patients who underwent endoscopic transnasal transsphenoidal pituitary tumor resection from June 2019 to June 2021. Univariate and multivariate logistic regression analyses were used to screen for independent risk factors for nasal bleeding from the training set. A multivariate logistic regression model was established, a nomogram was plotted, and it was validated in an internal validation set. The performance of the nomogram was evaluated based on the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). Results: The nomogram indicators included anticoagulant use, sphenoid sinus artery injury, nasal irrigation, platelet count (PLT), and constipation. The predictive model had an area under the ROC curve of 0.932 (95% CI: 0.873-0.990) and 0.969 (95% CI: 0.940-0.997) for the training and validation sets, respectively, indicating good discrimination. The calibration curve showed good consistency between the actual and predicted incidence of nasal bleeding (p > 0.05). DCA indicated that the nomogram had good clinical net benefit in predicting postoperative nasal bleeding in patients. Conclusion: In summary, this study explored the incidence and influencing factors of nasal bleeding after endoscopic transnasal transsphenoidal pituitary tumor resection and established a predictive model to assist clinical decision-making.

Approaches based on natural products and miRNAs in pituitary adenomas: unveiling therapeutic intervention.

Pituitary adenomas (PAs) are tumors originating in the pituitary gland, a small gland located at the base of the brain. They are the most common type of pituitary tumor, affecting approximately 1 in 10 people over their lifetime. Common symptoms include headaches, vision problems, hormonal imbalances, and weight changes. Treatment options depend on the type and size of the adenoma and may consist of medication, surgery, radiation therapy, or a combination. PAs are typically benign and slow-growing, but they can cause significant health issues if left untreated. Proper diagnosis and management by an experienced multidisciplinary team is important for achieving the best outcomes. Natural compounds like celastrol, curcumin, quercetin, apigenin, resveratrol, epigallocatechin gallate (EGCG), and genistein have shown the ability to inhibit cell growth, promote cell death, and suppress hormone activity in pituitary tumor cells, suggesting their potential as alternative or complementary treatments for PAs. MicroRNAs (miRNAs) are a kind of tiny RNA molecules that do not code for proteins and have a vital function in controlling gene expression. These 21-23 nucleotide-long molecules regulate gene expression by binding to complementary sequences in mRNA molecules, leading to mRNA degradation. miRNAs participate in a wide range of biological activities, including apoptosis, metastasis, differentiation, and proliferation. The research indicates that miRNAs play a crucial role in the pathogenesis, therapeutic approaches, diagnosis, and prognosis of PAs. This review article will provide a comprehensive analysis of the current understanding of the efficacy of naturally derived anti-cancer agents in the treatment of PAs. Furthermore, the study provides a comprehensive assessment of the miRNAs in PAs, their role in the development of PAs, and their potential application in the treatment of the condition.

KLHL14 and E-Cadherin Nuclear Co-Expression as Predicting Factor of Nonfunctioning PitNET Invasiveness: Preliminary Study.

Background/Objectives. Novel diagnostic and therapeutic approaches are needed to improve the clinical management of nonfunctioning pituitary neuroendocrine tumors (NF-PitNETs). Here, the expression of two proteins controlling the epithelial-mesenchymal transition (EMT)-an underlying NF-PitNET pathogenic mechanism-were analyzed as prognostic markers: E-cadherin (E-Cad) and KLHL14. Methods. The immunohistochemistry characterization of KLHL14 and E-Cad subcellular expression in surgical specimens of 12 NF-PitNET patients, with low and high invasiveness grades (respectively, Ki67+ < and ≥3%) was carried out. Results. The analysis of healthy vs. NF-PitNET tissues demonstrated an increased protein expression and nuclear translocation of KLHL14. Moreover, both E-Cad and KLHL14 shifted from a cytoplasmic (C) form in a low invasive NF-PitNET to a nuclear (N) localization in a high invasive NF-PitNET. A significant correlation was found between E-Cad/KLHL14 co-localization in the cytoplasm (p = 0.01) and nucleus (p = 0.01) and with NF-PitNET invasiveness grade. Conclusions. Nuclear buildup of both E-Cad and KLHL14 detected in high invasive NF-PitNET patients highlights a novel intracellular mechanism governing the tumor propensity to local invasion (Ki67+ ≥ 3%). The prolonged progression-free survival trend documented in patients with lower KLHL14 expression further supported such a hypothesis even if a larger cohort of NF-PitNET patients have to be analyzed to definitively recognize a key prognostic role for KLHL14.

Novel classification of gastric polyps: The good, the bad and the ugly.

Gastric polyps (GPs) are increasingly common. On upper endoscopy, they should be examined with white light and occasionally chromoendoscopy, and their morphology classified according to the Paris classification. Most GPs have a typical endoscopic appearance and can be associated with diseases like Helicobacter pylori infection. Histological examination is necessary for an accurate diagnosis. While most polyps are non-neoplastic and do not require treatment, some carry a risk of malignancy or are already malignant. Therefore, understanding the diagnosis, classification, and management of GPs is crucial for patient prognostication. Our new classification categorizes GPs into "good", "bad", and "ugly" based on their likelihood of becoming malignant. We aim to provide descriptions of the endoscopic appearance, pathology, treatment, and follow-up for different GPs, as well as clinical management flowcharts.

Transcecal endoscopic appendectomy for management of complex appendiceal polyps extending into the appendiceal orifice.

Background and study aims Endoscopic resection of appendiceal orifice (AO) polyps extending inside the appendiceal lumen is challenging given the inability to determine polyp lateral margins and risk of appendicitis. Transcecal endoscopic appendectomy (TEA) ensures en bloc resection of these complex polyps. Patients and methods This case series includes patients who underwent TEA by a single endoscopist in the United States. Technical success was defined as achieving complete removal of the appendix along with AO polyp in an en bloc fashion. Results In total, nine patients were included (mean age 69.7 ± 9.6 years). The average appendix size was 4.07 ± 2.02 cm. Technical success was achieved in 100% of the patients. The average procedure length was 118.1 ± 44.21 minutes. The en bloc resection rate, R0 resection rate, and curative resection rates were 100%. Patients were observed for an average of 3.1 ± 1.6 days. One patient developed loculated fluid collection 9 days post procedure, which resolved on its own with oral antibiotic therapy. No other adverse events were recorded. Conclusions This was an early study of the feasibility of TEA in the United States. This novel technique, in early-stage development, is potentially safe and associated with a minimal risk profile in expert hands. Further prospective studies are needed to standardize the technique.

Loop9 closure technique for mucosal defects after colorectal endoscopic submucosal dissection (with video).

Background and study aims Mucosal defect closure after colorectal endoscopic submucosal dissection (ESD) has the potential to reduce the occurrence of delayed adverse events (AEs) such as bleeding and perforation. This study aimed to assess the feasibility and effectiveness of the Loop9 method for closing mucosal defects following colorectal ESD. Patients and methods A retrospective single-center study was conducted using prospectively collected data from May 2020 to March 2023. Loop9 was deployed through a single instrument channel and anchored with clips at the defect site. Closure was accomplished by tightening the loop and deploying additional conventional clips as needed for complete closure. The primary outcome was complete closure rate, with secondary outcomes including the sustained closure rate at 4 to 5 days post-ESD, closed defect size, closure time, number of additional clips, and incidence of delayed AEs. Results This study included 118 cases. Complete closure was achieved in 96.6% of cases (114/118) with a sustained closure rate of 93.9% (107/114). The median size of the closed mucosal defects was 30 mm (interquartile range [IQR]: 25-38, range: 15-74). The median closure time was 14 minutes (IQR: 11.25-17), and the median number of additional clips deployed was six (IQR: 4-7). Stenosis requiring balloon dilatation was observed in one patient; however, there were no instances of post-ESD bleeding or delayed perforation. Conclusions The Loop9 method proved feasible and effective for closing mucosal defects following colorectal ESD, achieving high rates of complete and sustained closure.

Outcome after colorectal full-thickness resection and management of recurrence.

Background and study aims Endoscopic full-thickness resection (eFTR) allows treatment of "difficult to resect" lesions not amenable to conventional endoscopic methods. Efficacy and safety of the system have already been proven in numerous studies. Follow-up data on outcome of colorectal eFTR and management of recurrences are still rare. Patients and methods All patients undergoing colorectal eFTR at our institution with at least one endoscopic follow-up examination were retrospectively analyzed. The primary endpoint was the rate of recurrent or residual lesions (RRLs) and the secondary endpoint was the rate of late adverse events (AEs). We further aimed to identify risk factors for RRLs and to describe their management. Results Between November 2014 and 2021, 141 patients underwent eFTR at University Medical Center Freiburg. Ninety-one patients fulfilled the inclusion criteria. Indications for eFTR were non-lifting adenoma (n = 65), subepithelial tumors (n = 18) and early carcinoma (n = 8). The median follow-up period was 17 months (range, 2-86). The overall RRL rate was 9.9% (9/91). A significant proportion of RRLs (6/9, 66%) were detected late. All RRLs occurred in the group of non-lifting adenoma, corresponding to a RRL rate of 13.8% in this subgroup. Thirty-three percent (3/9) were initially treated by hybrid eFTR. Of the RRLs, 66.6% could were successfully treated endoscopically. On χ2 analysis, the hybrid eFTR technique ( P = 0.006) was associated with a higher rate of RRL. No late AEs occurred. Conclusions The rate of RRL after colorectal eFTR is low and the majority could be treated endoscopically. For non-lifting adenomas and early carcinomas, close follow-up is mandatory to detect late recurrence. Long-term outcomes after hybrid eFTR need further investigation.

Pleomorphic Adenoma - A Case Report on an Abnormal Mass.

Rationale: Pleomorphic adenoma (PA) is the most prevalent salivary gland tumour, accounting for 60%-80% of all benign salivary gland tumours, and frequently affects the parotid gland. Their epithelial and connective tissue origins can explain the 'pleomorphic' nature of tumours. This tumour is most common in women between 30 and 50 years. Patient Concerns: A 45-year-old female came with the chief complaint of a slow-growing, painless swelling on the left side of her face that had been present for 25 years. Diagnosis: PA of the parotid gland was diagnosed using computed tomography and fine-needle aspiration cytology. PA is a slowly progressing, asymptomatic swelling that rarely exceeds 6 cm in its greatest dimension; in our case, it was 13 cm × 10 cm and weighed 5 kg. Treatment: The ideal management is the surgical removal of the tumour mass, which was done under general anaesthesia. Early diagnosis and treatment planning was critical. Complete removal of the tumour without remnants is crucial to prevent a recurrence. Total parotidectomy was done in this case. Outcomes: There was no evidence of recurrence after comprehensive local surgical resection of the tumour during the follow-up period. Take-away Lessons: This case report is significant as it sheds light on the successful treatment approach for a large pleomorphic adenoma. It can provide valuable insights into the management of similar cases, potentially leading to improved patient outcomes and guiding future treatment strategies.

Exploring Vitamin D Deficiency and IGF Axis Dynamics in Colorectal Adenomas.

(1) Colorectal cancer is a major cause of cancer-related death, with colorectal adenomas (CRAs) serving as precursors. Identifying risk factors such as vitamin D deficiency and the insulin-like growth factor (IGF) axis is crucial for prevention. (2) This case-control study included 85 participants (53 CRA patients and 32 controls) who underwent colonoscopy. We measured serum vitamin D3 (cholecalciferol), calcidiol (vitamin D metabolite), calcitriol (active vitamin D metabolite), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-3 (IGFBP-3) to explore their associations with CRA risk. (3) Results: We found that lower cholecalciferol levels were a significant risk factor for CRA (OR = 4.63, p = 0.004). Although no significant differences in calcidiol and calcitriol levels were observed between CRA patients and controls, calcidiol deficiency was common in the study population. IGF-1 levels inversely correlated with age, calcitriol, and IGFBP-3 in CRA patients. (4) This study highlights the potential of lower cholecalciferol levels to detect patients at risk of CRA when calcidiol values cannot, suggesting the importance of evaluating different vitamin D metabolites in cancer prevention research. Our findings underscore the need to further investigate the interactions between calcitriol, the active form of vitamin D, and the IGF axis in colorectal cancer development.

The value of diffusion kurtosis imaging and dynamic contrast-enhanced magnetic resonance imaging in the differential diagnosis of parotid gland tumors.

Background: Parotid gland tumors (PGTs) are the most common benign tumors of salivary gland tumors. However, the diagnostic value of relative values of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion kurtosis imaging (DKI) parameters for PGTs has not been extensively studied. Therefore, this study aimed to evaluate the diagnostic performance of combined DKI and DCE-MRI for differentiating PGTs by introducing the concept of relative value. Methods: The DCE-MRI and DKI imaging data of 142 patients with PGTs between June 2018 and August 2022 were collected. Patients were divided into four groups by histopathology: malignant tumors (MTs), pleomorphic adenomas (PAs), Warthin tumors (WTs), and basal cell adenomas (BCAs). All MRI examinations were conducted using a 3 T MRI scanner with a 20-channel head and neck coil. Quantitative parameters of DCE-MRI and DKI and their relative values were determined. Kruskal-Wallis H test, post-hoc test with Bonferroni correction, one-way analysis of variance (ANOVA) and post-hoc test with least significant difference (LSD) method, and the receiver operating characteristic (ROC) curve were used for statistical analysis. Statistical significance was set at P<0.05. Results: Only the combination of DKI and DCE-MRI parameters could reliably distinguish BCAs from other PGTs. PAs demonstrated the lowest transfer constant from plasma to extravascular extracellular space (Ktrans) value [0.09 (0.06, 0.20) min-1], relative Ktrans (rKtrans) [-0.24 (-0.64, 1.00)], rate constant from extravascular extracellular space to plasma (Kep) value [0.32 (0.22, 0.53) min-1], relative Kep (rKep) [0.32 (0.22, 0.53) min-1], and initial area under curve (iAUC) value [0.15 (0.09, 0.26) mmol·s/kg] compared with WTs, BCAs, and MTs (all P<0.05). The Ktrans values for MTs were substantially lower [0.17 (0.10, 0.31) min-1] than those for WTs (P=0.01). The Kep values for MTs [0.71 (0.52, 1.28) min-1] were substantially lower (all P<0.05) than those for WTs and BCAs. PAs and BCAs had higher diffusion coefficient (D) values and lower diffusion kurtosis (K) values and relative K (rK) values than MTs and WTs. However, the D and K values did not differ significantly even in their relative values of PAs and BCAs (all P>0.05). By using logistic regression, the combination of K value and rKep value further enhanced their discriminatory power between PAs and WTs [area under the ROC curve (AUC), 0.986], the combination of K and rKep value further enhanced their discriminatory power between PAs and MTs (AUC, 0.915), and the combination of D and Kep value further enhanced their discriminatory power between BCAs and MTs (AUC, 0.909). Conclusions: DKI and DCE-MRI can be used to differentiate PGTs quantitatively and can complement each other. The combined use of DKI and DCE-MRI parameters can improve the diagnostic accuracy of distinguishing PGTs.

Does New WHO 2022 Nomenclature of Pituitary Neuroendocrine Tumors Offer an Extra Edge to the Neurosurgeons for Its Management? A Narrative Review.

The new World Health Organization nomenclature of pituitary tumors was introduced in the year 2022 after much deliberation. This nomenclature clearly demarcates the anterior lobe (adenohypophyseal), posterior lobe (neurohypophyseal), and hypothalamic tumors. There is also focus on other tumors arising in the sellar region. The nomenclature has also advocated the routine use of immunohistochemistry in describing the pituitary transcription factors that plays a fundamental role in distinguishing the cell lineage of these tumors. However, the nomenclature is complex in understanding due to inclusion of pathological correlates like transcription factors, hormones, biomarkers, and various controversies that have emerged regarding the renaming of pituitary adenomas (PA) as PiTNETs ("Pituitary Neuroendocrine tumors") because majority of the adenomas are benign and have rare metastatic behavior while classifying them as PiTNETs will create unnecessary misinterpretation of these as aggressive tumors that will lead to apprehension among the patients. The new classification gives deeper insight into the histological picture of the various pituitary tumors but other than contributing to the follow-up strategy and postsurgery management, this classification does not add anything new that could be advantageous for the neurosurgeons in clinical practice and decision making, especially in deciding the plan of action for surgery. Hence, there is need of a more comprehensive, integrated, neuroradiological-based classification with more emphasis on the invasiveness of these tumors that would assist the neurosurgeons in planning the treatment strategy and managing patients of pituitary tumors.