Diagnostic utility of RAS mutation testing for refining cytologically indeterminate thyroid nodules.

RAS mutations are prevalent in indeterminate thyroid nodules, but their association with malignancy risk and utility for diagnosis remains unclear. We performed a systematic review and meta-analysis to establish the clinical value of RAS mutation testing for cytologically indeterminate thyroid nodules. PubMed and Embase were systematically searched for relevant studies. Thirty studies comprising 13,328 nodules met the inclusion criteria. Random effects meta-analysis synthesized pooled estimates of RAS mutation rates, risk of malignancy with RAS positivity, and histologic subtype outcomes. The pooled mutation rate was 31 % (95 % CI 19-44 %) among 5,307 indeterminate nodules. NRAS mutations predominated at 67 % compared to HRAS (24 %) and KRAS (12 %). The malignancy rate with RAS mutations was 58 % (95 %CI=48-68 %). RAS positivity increased malignancy risk 1.7-fold (RR 1.68, 95 %CI=1.21-2.34, p=0.002), with significant between-study heterogeneity (I2=89 %). Excluding one outlier study increased the relative risk to 1.75 (95 %CI=1.54-1.98) and I2 to 14 %. Funnel plot asymmetry and Egger's test (p=0.03) indicated potential publication bias. Among RAS-positive malignant nodules, 38.6 % were follicular variant papillary carcinoma, 34.1 % classical variant, and 23.2 % follicular carcinoma. No statistically significant difference in the odds of harboring RAS mutation was found between subtypes. In conclusion, RAS mutation testing demonstrates clinical utility for refining the diagnosis of cytologically indeterminate thyroid nodules. Positivity confers a 1.7-fold increased malignancy risk, supporting use for personalized decision-making regarding surgery vs. monitoring. Follicular variant papillary carcinoma constitutes the most common RAS-positive malignant histological subtype. See also the graphical abstract(Fig. 1).

GEMIN4 Variants: Risk Profiling, Bioinformatics, and Dynamic Simulations Uncover Susceptibility to Bladder Carcinoma.

BACKGROUND: The relationship between GEMIN4 genetic variants and cancer, especially bladder carcinoma (BLCA), has been explored without conclusive results. This study aims to elucidate the link between GEMIN4 polymorphisms and BLCA susceptibility through genetic analyses, bioinformatics, and molecular dynamics (MD) simulations. METHODS: A cohort of 249 participants (121 BLCA patients and 128 unrelated controls) was enrolled. PCR was employed for allelic discrimination of GEMIN4 variants, followed by subgroup stratification, haplotype analyses, structural prediction using the AlphaFold2 prediction tool, subsequent MD simulations, structural analysis, and residue interaction mapping using Desmond, UCSF ChimeraX, and Cytoscape softwares. RESULTS: The rs.2740348*G variant demonstrated a protective role against BLCA in allelic (OR = 0.55, p = 0.002) and recessive (OR = 0.54, p = 0.017) models, whereas the rs.7813*T variant increased BLCA risk under the recessive model (OR = 1.90, p = 0.019). Haplotype analysis revealed a significant association between GEMIN4 haplotype (rs.2740348*C/rs.7813*T) with increased BLCA risk (OR = 2.01, p = 0.004). Univariate analysis revealed associations of the variants with albumin levels and absolute neutrophil count in BLCA patients. Pathogenicity evaluation categorized p.Gln450Glu as neutral and p.Arg1033Cys as deleterious. MD simulations revealed structural alterations and conformational shifts in the GEMIN4 protein induced by the Glu450 and Cys1033 mutations. CONCLUSIONS: The study highlights the dual role of GEMIN4 variants in BLCA susceptibility, with rs.2740348 conferring protection and rs.7813 increasing risk. The Glu450 residue positively impacted protein stability, while Cys1033 had a detrimental effect on protein function. These findings underscore the significance of GEMIN4 variants in BLCA susceptibility and pave the way for future diagnostic and therapeutic initiatives.

Clinical outcomes and tumor microenvironment response to radiofrequency ablation therapy: a systematic review and meta-analysis.

Background: Radiofrequency ablation (RFA) utilizes minimally invasive high-energy current to precisely ablate tumor cells. It has been utilized in many cancer types including thyroid, lung, and liver cancer. It has been shown to provide adequate ablative margins with minimal complications; however, incomplete RFA may lead to recurrence of tumor. The underlying cellular mechanism and behavior of ablated cancer tissue is poorly understood. Methods: A systematic review was performed, searching EMBASE, Web of Science, PubMed, and Scopus for studies published up to March 2022 and reported following PRISMA guidelines. Collection was performed by two groups of investigators to avoid risk of bias. The Cochrane Collaboration's tool was used for assessing risk of bias. We identified human, in vivo, and in vitro research studies utilizing RFA for tumor tissues. We required that the studies included at least one of the following: complications, recurrence, or survival, and took interest to studies identifying cellular signaling pathway patterns after RFA. Descriptive statistical analysis was performed in 'R' software including mean and confidence interval. Results: The most frequent cancers studied were liver and lung cancers accounting for 57.4% (N=995) and 15.4% (N=267), followed by esophageal (N=190) and breast cancer (N=134). The most common reported complications were bleeding (19%) and post-operative pain (14%). In our literature search, four independent studies showed upregulation and activation of the VEGF pathway following RFA, four showed upregulation and activation of the AKT pathway following RFA, three studies demonstrated involvement of matrix metalloproteinases, and four showed upregulation of c-Met protein following RFA. Conclusions: In our review and meta-analysis, we identify several proteins and pathways of interest of which are important in wound healing, angiogenesis, and cellular growth and survival. These proteins and pathways of interest may implicate areas of research towards RFA resistance and cancer recurrence.

Assessing Adequacy: A Meta-Analysis of Rapid Onsite Evaluation of Thyroid Nodules.

INTRODUCTION: Fine-needle aspiration (FNA) is the standard form of preoperative evaluation of thyroid nodule cytological status. A significant number FNAs are classified as inadequate for interpretation, requiring a repeat FNA which is potentially avoidable, costly, and delays treatment. To address these concerns and maximize first-time FNA adequacy, rapid onsite evaluation (ROSE) of FNA specimens was introduced. Our study aims to determine the impact of ROSE on FNA adequacy. METHODS: PubMed, Embase, and Web of Science were searched for primary articles assessing the adequacy of ROSE in thyroid nodules. RESULTS: A total of 17 studies were included for a total of 24,649 thyroid nodes. Thirteen thousand two hundred fifteen (53.6%) thyroid nodules were assessed utilizing ROSE and 11,434 (46.4%) were not. Pooled adequacy increased significantly from 76% without ROSE to 92% with rose (P = 0.001). Use of ROSE increased the odds of adequate FNA by 22% (risk ratio (RR) = 1.22, 95% confidence interval (CI) = 1.12-1.32). At institutions with less than 85% effective diagnostic adequacy without ROSE, the risk for diagnostic adequacy increased by 28% with ROSE implementation (RR = 1.28, 95% CI = 1.20-1.37). In contrast, in studies reported from institutions with an effective diagnostic rate greater than 85% without the use of ROSE, the diagnostic adequacy only increased by 5% with ROSE implementation (RR = 1.05, 95% CI = 1.03-1.06). CONCLUSIONS: The use of ROSE during first-time FNA of thyroid nodules can significantly improve adequacy, especially at institutions with baseline high inadequacy rates. Implementation of ROSE can reduce repeat FNAs and its associated consequences.

Angio-Long Noncoding RNA MALAT1 (rs3200401) and MIAT (rs1061540) Gene Variants in Ovarian Cancer.

The genotyping of long non-coding RNA (lncRNA)-related single-nucleotide polymorphisms (SNPs) could be associated with cancer risk and/or progression. This study aimed to analyze the angiogenesis-related lncRNAs MALAT1 (rs3200401) and MIAT (rs1061540) variants in patients with ovarian cancer (OC) using "Real-Time allelic discrimination polymerase chain reaction" in 182 formalin-fixed paraffin-embedded (FFPE) samples of benign, borderline, and primary malignant ovarian tissues. Differences in the genotype frequencies between low-grade ovarian epithelial tumors (benign/borderline) and malignant tumors and between high-grade malignant epithelial tumors and malignant epithelial tumors other than high-grade serous carcinomas were compared. Odds ratios (ORs)/95% confidence intervals were calculated as measures of the association strength. Additionally, associations of the genotypes with the available pathological data were analyzed. The heterozygosity of MALAT1 rs3200401 was the most common genotype (47.8%), followed by C/C (36.3%). Comparing the study groups, no significant differences were observed regarding this variant. In contrast, the malignant epithelial tumors had a higher frequency of the MIAT rs1061540 C/C genotype compared to the low-grade epithelial tumor cohorts (56.7% vs. 37.6, p = 0.031). The same genotype was significantly higher in high-grade serous carcinoma than its counterparts (69.4% vs. 43.8%, p = 0.038). Multivariate Cox regression analysis showed that the age at diagnosis was significantly associated with the risk of OC development. In contrast, the MIAT T/T genotype was associated with a low risk of malignant epithelial tumors under the homozygote comparison model (OR = 0.37 (0.16-0.83), p = 0.017). Also, MIAT T allele carriers were less likely to develop high-grade serous carcinoma under heterozygote (CT vs. CC; OR = 0.33 (0.12-0.88), p = 0.027) and homozygote (TT vs. CC; OR = 0.26 (0.07-0.90), p = 0.034) comparison models. In conclusion, our data provide novel evidence for a potential association between the lncRNA MIAT rs1061540 and the malignant condition of ovarian cancer, suggesting the involvement of such lncRNAs in OC development.

Survival Outcomes of Medullary Thyroid Cancer With and Without Amyloid Deposition.

OBJECTIVE: Amyloid deposition within tumor stroma is a distinctive histologic feature of medullary thyroid cancer (MTC). However, its prognostic significance remains uncertain. We aimed to elucidate the impact of amyloid status on survival outcomes in a large cohort. METHODS: The Surveillance, Epidemiology, and End Results registry was queried to identify patients diagnosed with MTC from 2000 to 2019. Patients with amyloid-positive (International Classification of Diseases for Oncology, third edition code 8345/3) and amyloid negative (International Classification of Diseases for Oncology, third edition code 8510/3) tumors were analyzed. Overall and disease-specific survival were compared between matched cohorts using Kaplan-Meier and Cox proportional hazards analyses. RESULTS: Of the 2526 MTC patients, 511 of which were amyloid-positive and 2015 that were amyloid negative. Amyloid-positive patients displayed lower T stage (T3/4: 28% vs 85%, P < .001) and less extrathyroidal extension (11.3% vs 81.6%, P < .001). No difference in distant metastasis rate was observed between groups (14.5% vs 14.4%, P = .98). However, amyloid-positive patients showed a tendency for distal lymph node metastasis (1.2% vs 0.3%, P = .020). On univariate analysis, amyloid-positive status showed comparable overall survival times (mean 172.2 vs 177.8 months, P = .17), but a trend toward worse cancer-specific survival (hazard ratios [HR] = 1.31, 95% CI = 0.99-1.71, P = .051). After adjusting for covariates, amyloid deposition did not independently predict overall (HR = 1.15, 95% CI = 0.91-1.47, P = .25) or cancer-specific survival (HR = 1.30, 95% CI = 0.96-1.77, P = .09). Initiating therapy later than 1 month following diagnosis was associated with worse overall survival (HR = 1.25, 95% CI = 1.02-1.54, P = .029). CONCLUSIONS: The presence of amyloid in MTC paradoxically associates with lower T stage yet exhibits a trend toward worse cancer-specific mortality. Amyloid deposition alone does not independently influence prognosis. Delayed treatment adversely impacted overall survival.

Elucidating the link between thyroid cancer and mercury exposure: a review and meta-analysis.

Mercury (Hg) is a widely distributed and bioavailable metal of public health concern, with many known human toxicities, but data regarding mercury's influence on thyroid cancer (TC) is scarce. Mercury is known to impact several molecular pathways implicated in carcinogenesis, and its proclivity for bioaccumulation in the thyroid suggests a potential modulatory effect. We conducted a literature/systematic review of studies between 1995-2022 intending to define better and establish relationships between these two entities, congregate the evidence for mercury's potential role in thyroid carcinogenesis, and identify populations of interest for further study. Insufficient evidence precludes definitive conclusions on dietary mercury as a TC risk factor; however, several common mechanisms affected by mercury are crucial for TC development, including biochemical, endocrine, and reactive oxygen species effects. Quantitative analysis revealed associations between TC risk and mercury exposure. In three mercury studies, average urine levels were higher in TC patients, with a mean difference of 1.86 µg/g creatinine (95% CI = 0.32-3.41). In two studies investigating exposure to elevated mercury levels, the exposed group exhibited a higher risk of developing TC, with a relative risk of 1.90 (95% CI = 1.76-2.06). In three thyroid tissue studies, mercury levels (ppm) were higher in TC patients, averaging 0.14 (0.06-0.22) in cancerous cases (N = 178) and 0.08 (0.04-0.11) in normal thyroids (N = 257). Our findings suggest an association between mercury exposure and TC risk, implying a possible predisposing factor. Further research is necessary to reveal the clinical relevance of dietary and environmental mercury exposures in TC pathogenesis.

Risk Factors for Postoperative Infections Following Appendectomy of Complicated Appendicitis: A Meta-analysis and Retrospective Single-institutional Study.

Patients with complicated appendicitis have an increased risk for postoperative infections. Potential risk factors for postoperative infections through a meta-analysis and retrospective chart review are discussed. A meta-analysis consisting of 35 studies analyzing complicated appendicitis treated with an appendectomy noting at least 1 postoperative infection was performed. A retrospective review was then conducted in patients diagnosed with complicated appendicitis after appendectomy. Of 5326 patients in total, 15.4% developed postoperative infections. Laparoscopic surgery and perioperative hyperoxygenation were found to be protective factors for the development of infection. Retrospectively, 53.2% of patients presented with complicated appendicitis. Patients with complicated appendicitis were more likely to be older in age and have an increased length of stay. Patient demographics, operative time, and comorbid status had no effect on postoperative infection or readmission rate. Physicians should strongly consider minimally invasive techniques to treat all cases of complicated appendicitis irrespective of comorbidities, age, sex, or body mass index.

Survival benefits of extensive surgery in patients with papillary thyroid microcarcinoma.

BACKGROUND: Despite the guidelines recommending thyroid lobectomy, many papillary thyroid microcarcinoma (PTMC) patients still undergo total thyroidectomy. PTMC's optimal treatment remains unclear. We aimed to determine whether total thyroidectomy improves outcomes compared to less extensive surgery. METHODS: We analyzed 6064 PTMC adult patients from the Surveillance, Epidemiology, and End Results (SEER) database (2000-2019) who underwent either total thyroidectomy (n â€‹= â€‹3652) or less extensive surgery (n â€‹= â€‹2412). Endpoints were overall survival, cancer-specific survival, and recurrence. RESULTS: Total thyroidectomy patients had a 5.2 â€‹% mortality rate versus 8.1 â€‹% with less extensive surgery. Recurrence occurred in 1 (0.03 â€‹%) total thyroidectomy patient compared to 24 (1.0 â€‹%) less extensive surgery patients (HR 0.07, p â€‹= â€‹0.01). Median survival was 8.1 years for total thyroidectomy versus 8.8 years for less extensive surgery. Overall survival favored total thyroidectomy (p â€‹= â€‹0.001) but cancer-specific survival did not differ. CONCLUSION: Although total thyroidectomy may not improve cancer-specific survival, it lowers recurrence risk and confers an overall survival advantage for PTMC patients. These findings may help guide surgical decisions.

Completion thyroidectomy: A safe option for high-volume surgeons.

BACKGROUND: The risk of complication in patients undergoing completion thyroidectomy (cT) is mixed. Several studies report increased risk in comparison to total thyroidectomy (TT) and still others reporting a comparatively decreased risk. We compared the rates of complication in patients at our institution undergoing thyroid lobectomy (TL), (TT), and cT by a single high-volume surgeon. METHODS: We performed a single-institution retrospective cohort study. Patients undergoing TL, TT, or cT by a high-volume surgeon were included. Rates of complication were collected and compared between the three cohorts. RESULTS: A total of 310 patients were included. The overall rate of complication was 4.2%. The complication rates in the TL, TT, and cT cohorts were 1%, 7.1%, and 4.5%, respectively (p = 0.10). Transient hypocalcemia was slightly more common in the TT cohort (6.1%) as opposed to the TL (0%) or cT (0.9%) cohort (p = 0.01). The cohorts also had similar rates of recurrent laryngeal nerve signal loss leading to transient dysphonia (TL: 0% vs. TT: 1% vs. cT: 3.6%, p = 0.10). CONCLUSIONS: While rates of complication tended to predictably decrease as approaches became less extensive, there were no significant differences in complication rates among the three surgical approaches when performed by a high-volume surgeon. Considering the low rates of complication overall, patient counseling and preference should be emphasized to provide appropriate and tailored treatment plans.

From ablation to operation: Unraveling the surgical outcomes and complications of thyroidectomy after radiofrequency ablation.

BACKGROUND: Radiofrequency ablation is a minimally invasive treatment for thyroid nodules; however, concerns exist regarding its impact on subsequent thyroid surgery. We compared surgical outcomes and complications between patients undergoing thyroidectomy after radiofrequency ablation (post-radiofrequency ablation thyroidectomy group) and those without prior radiofrequency ablation (non-radiofrequency ablation thyroidectomy group). METHODS: We retrospectively analyzed thyroidectomy patients, comparing post-radiofrequency ablation thyroidectomy and non-radiofrequency ablation thyroidectomy groups, examining demographics, nodule characteristics, surgical techniques, and complications. RESULTS: The study included 96 patients (73 in the non-radiofrequency ablation thyroidectomy group and 23 in the post-radiofrequency ablation thyroidectomy group). The mean age was 53.3 ± 14.4 years, with 78.1% female patients and 36.5% African American patients. Median operative time was similar between the post-radiofrequency ablation thyroidectomy (110 minutes) and the non-radiofrequency ablation thyroidectomy (92 minutes) cohorts (P = .40). Complications were reported in 13 patients, without significant differences between groups (P = .54). No permanent complications, including nerve injury or hypoparathyroidism, were reported in either cohort. Prior radiofrequency ablation treatment did not increase the risk of complications (odds ratio = 3.48, 95% confidence interval = 0.70-17.43, P = .16). CONCLUSION: Our work found no differences in outcomes or safety in patients undergoing thyroidectomy with or without previous radiofrequency ablation treatment, potentiating the post-radiofrequency ablation thyroidectomy group as a safe management option. Accordingly, this may reassure both clinicians and patients of the safety of radiofrequency ablation in treating patients with thyroid nodules.

Radiofrequency ablation of benign thyroid nodules: A prospective, multi-institutional North American experience.

BACKGROUND: Radiofrequency ablation for benign thyroid nodules aims to achieve a volume reduction rate of ≥50%. However, factors that predict treatment success have not been defined in a large-scale study. METHODS: A prospective cohort study of biopsy-proven benign thyroid nodules treated with radiofrequency ablation at 3 institutions was performed. Patient demographics, nodule sonographic features, procedural data, and nodule volume reduction were evaluated. Binary logistic regression analysis was performed to identify features associated with treatment response. RESULTS: A total of 620 nodules were analyzed. The pooled median volume reduction rate at 12 months was 70.9% (interquartile range 52.9-86.6). At 1 year follow-up, 78.4% of nodules reached treatment success with a volume reduction rate ≥50%. The overall complication rate was 3.2% and included temporary voice changes (n = 14), vasovagal episodes (n = 5), nodule rupture (n = 3), and lightheadedness (n = 2). No permanent voice changes occurred. Four patients developed postprocedural hypothyroidism. Large baseline nodule volume (>20 mL) was associated with a lower rate of successful volume reduction (odds ratio 0.60 [0.37-0.976]). Large nodules achieved treatment success by 12-month follow-up at a rate of 64.5%, compared with 81.4% for small nodules and 87.2% for medium nodules. CONCLUSION: To our knowledge, this is the largest North American cohort of patients with benign thyroid nodules treated with radiofrequency ablation. Overall, radiofrequency ablation was an effective treatment option with a low risk of procedural complications. Large volume nodules (>20 mL) may be associated with a lower rate of successful reduction with radiofrequency ablation treatment.

Circulating ESR1, long non-coding RNA HOTAIR and microRNA-130a gene expression as biomarkers for breast cancer stage and metastasis.

Breast cancer, the most prevalent cancer among women, has posed a significant challenge in identifying biomarkers for early diagnosis and prognosis. This study aimed to elucidate the gene expression profile of Estrogen Receptor-1 (ESR-1), long non-coding RNA HOTAIR, and microRNA-130a in the serum of Egyptian breast cancer patients, evaluating the potential of HOTAIR and miR-130a as biomarkers for predicting pathological parameters in BC. The study involved 45 patients with primary BC, with serum samples collected preoperatively and postoperatively twice. The expression levels of ESR-1, HOTAIR, and miR-130a were quantified using real-time PCR and analyzed for correlations with each other and with the clinical and pathological parameters of the patients. Serum HOTAIR levels exhibited a strong positive association with metastasis and demonstrated a significant increase after 6 months in all patients with locally advanced and stage IV BC. Conversely, tumors with advanced stages and metastatic lesions showed significantly lower expression levels of miR-130a. Notably, a significant positive correlation was observed between preoperative ESR-1 expression and both HOTAIR and miR-130a levels. Serum HOTAIR and miR-130a levels have emerged as promising non-invasive biomarkers with the potential to predict the pathological features of BC patients. HOTAIR, an oncogenic long non-coding RNA (lncRNA), and miR-130a, a tumor suppressor miRNA, play crucial roles in tumor progression. Further investigations are warranted to elucidate the intricate interplay between HOTAIR and miR-130a and to fully comprehend the contribution of HOTAIR to BC recurrence and its potential utility in early relapse prediction.

Matrix Metalloproteinase 9/microRNA-145 Ratio: Bridging Genomic and Immunological Variabilities in Thyroid Cancer.

Matrix metalloproteinase 9 (MMP9) and microRNA-145 (miR-145) have emerged as essential biomarkers in thyroid cancer progression and metastasis. However, their combined evaluation and clinical utility as a unified prognostic marker across diverse thyroid cancer subgroups remain unexplored. We investigated the diagnostic and prognostic value of the MMP9/miR-145 ratio in thyroid cancer, hypothesizing it may overcome inter-patient heterogeneity and serve as a versatile biomarker regardless of genetic mutations or autoimmune status. MMP9 and miR-145 expressions were analyzed in 175 paired papillary thyroid cancer (PTC) and normal tissues. Plasma levels were assessed perioperatively and longitudinally over 12-18 months in 86 matched PTC patients. The associations with clinicopathological parameters and patient outcomes were evaluated. MMP9 was upregulated, and miR-145 downregulated in cancer tissues, with a median MMP9/miR-145 ratio 17.6-fold higher versus controls. The tissue ratio accurately diagnosed thyroid malignancy regardless of BRAF mutation or Hashimoto's thyroiditis status, overcoming genetic and autoimmune heterogeneity. A high preoperative circulating ratio predicted aggressive disease features, including lymph node metastasis, extrathyroidal extension, progression/relapse, and recurrence. Although the preoperative plasma ratio was elevated in patients with unfavorable outcomes, it had limited utility for post-surgical monitoring. In conclusion, the MMP9/miR-145 ratio is a promising biomarker in PTC that bridges genetic and immunological variabilities, enhancing preoperative diagnosis and prognostication across diverse patient subgroups. It accurately stratifies heterogenous cases by aggressiveness. The longitudinal trends indicate decreasing applicability for post-thyroidectomy surveillance. Further large-scale validation and protocol standardization can facilitate clinical translation of the MMP9/miR-145 ratio to guide personalized thyroid cancer management.

The blockage signal for PD-L1/CD274 gene variants and their potential impact on lung carcinoma susceptibility.

BACKGROUND: The programmed death-ligand 1 (PD-L1/CD274) gene plays a key function in suppressing anti-tumor immunity through binding to its receptor PD-1 on stimulated T lymphocytes. However, robust associations among diverse populations and lung susceptibility remain unclear. The tentative purpose of this research is to investigate whether PD-L1/CD274 polymorphisms modulate susceptibility to lung carcinoma using totalitarian techniques, including genetic analysis, and sophisticated bioinformatic methods. METHODS: PD-L1/CD274 (rs822336, rs2297136, and rs4143815) variants were genotyped in 126 lung carcinoma cases and 117 healthy controls using tetra-primer ARMS-PCR. Logistic regression and bioinformatics analyses assessed genetic associations. RESULTS: The rs2297136 GA genotype significantly increased lung cancer risk by 3.7-fold versus GG genotype (OR 3.69, 95 % CI 1.39-9.81, p = 0.016), with the minor A allele also increasing risk (OR 1.47, p = 0.044). In contrast, the rs4143815 CC genotype was associated with 70 % decreased cancer risk versus GG (OR 0.30, 95 % CI 0.11-0.87, p = 0.012), although the minor C allele itself was not significant. The rs822336 variant showed no association. Haplotype and multivariate analyses supported these findings. In silico predictions suggested functional impacts on PD-L1 expression and activity. CONCLUSIONS: This study identified novel associations between PD-L1/CD274 polymorphisms and susceptibility to lung cancer in Egyptians. The rs2297136 variant increased risk while the rs4143815 variant conferred protection, highlighting the PD-1/PD-L1 axis as a potential biomarker and therapeutic target in lung oncogenesis. Replication in larger cohorts and functional studies are warranted.

Vaping, Environmental Toxicants Exposure, and Lung Cancer Risk.

Lung cancer (LC) is the second-most prevalent tumor worldwide. According to the most recent GLOBOCAN data, over 2.2 million LC cases were reported in 2020, with an estimated new death incident of 1,796,144 lung cancer cases. Genetic, lifestyle, and environmental exposure play an important role as risk factors for LC. E-cigarette, or vaping, products (EVPs) use has been dramatically increasing world-wide. There is growing concern that EVPs consumption may increase the risk of LC because EVPs contain several proven carcinogenic compounds. However, the relationship between EVPs and LC is not well established. E-cigarette contains nicotine derivatives (e.g., nitrosnornicotine, nitrosamine ketone), heavy metals (including organometal compounds), polycyclic aromatic hydrocarbons, and flavorings (aldehydes and complex organics). Several environmental toxicants have been proven to contribute to LC. Proven and plausible environmental carcinogens could be physical (ionizing and non-ionizing radiation), chemicals (such as asbestos, formaldehyde, and dioxins), and heavy metals (such as cobalt, arsenic, cadmium, chromium, and nickel). Air pollution, especially particulate matter (PM) emitted from vehicles and industrial exhausts, is linked with LC. Although extensive environmental exposure prevention policies and smoking reduction strategies have been adopted globally, the dangers remain. Combined, both EVPs and toxic environmental exposures may demonstrate significant synergistic oncogenicity. This review aims to analyze the current publications on the importance of the relationship between EVPs consumption and environmental toxicants in the pathogenesis of LC.

Type 2 diabetes and thyroid cancer: Synergized risk with rising air pollution.

Diabetes is a complex condition, and the causes are still not fully understood. However, a growing body of evidence suggests that exposure to air pollution could be linked to an increased risk of diabetes. Specifically, exposure to certain pollutants, such as particulate Matter and Ozone, has been associated with higher rates of diabetes. At the same time, air pollution has also been linked to an increased risk of thyroid cancer. While there is less evidence linking air pollution to thyroid cancer than to diabetes, it is clear that air pollution could have severe implications for thyroid health. Air pollution could increase the risk of diabetes and thyroid cancer through several mechanisms. For example, air pollution could increase inflammation in the body, which is linked to an increased risk of diabetes and thyroid cancer. Air pollution could also increase oxidative stress, which is linked to an increased risk of diabetes and thyroid cancer. Additionally, air pollution could increase the risk of diabetes and thyroid cancer by affecting the endocrine system. This review explores the link between diabetes and air pollution on thyroid cancer. We will discuss the evidence for an association between air pollution exposure and diabetes and thyroid cancer, as well as the potential implications of air pollution for thyroid health. Given the connections between diabetes, air pollution, and thyroid cancer, it is essential to take preventive measures to reduce the risk of developing the condition.

Recommend with caution: A meta-analysis investigating papillary thyroid carcinoma tumor progression under active surveillance.

BACKGROUND: Papillary thyroid carcinoma (PTC) is an indolent disease with favorable outcomes. The non-surgical treatment approach known as active surveillance (AS) has been introduced as an alternative treatment instead of the traditional thyroidectomy. However, 10-15 % of PTC tend to progress. We sought to determine factors predicting the progression of PTC under AS. METHODS: A systematic search was performed in January 2022 using PubMed, Embase, Google Scholar, Web of Science, and ScienceDirect. PRISMA guidelines were used by multiple reviewers to extract study characteristics (author name, publication date, journal name, country, institution, and study design), as well as main outcomes and measures. A combination of utilization of thyroid replacement therapy, baseline tumor size and volume, follow-up tumor size and volume, and the presence of lymph node metastasis and its distribution, as well as surveillance duration, were the main measures of this study. RESULTS: Nine studies with 4166 patients were included, of which 354 showed tumor progression during AS (15 %; 95%CI = 7 % - 23 %). The average follow-up period was 41.58 months. The mean tumor maximum diameter was 8.54 mm (95%CI = 7.04-10.03). Tumor progression was most commonly secondary to an increase in volume by ≥50 % (75 %; 95%CI = 68 % - 80 %), then increase in diameter by ≥3 mm (41 %; 95%CI = 13 % - 76 %), and finally the development of lymph node metastasis (13 %; 95%CI = 9 % - 19 %). Approximately only 2 % of all patients thus developed new lymph node metastasis. Patient age, sex, and tumor size were not associated with higher risks of tumor progression. 12 % of AS patients eventually underwent surgery, though only 40 % (95%CI = 27 % - 53 %) of these patients displayed tumor progression. CONCLUSIONS: Our meta-analysis determined a tumor progression rate of 15 % in patients who underwent AS management, 13 % of which (2 % of all patients) developed lymph node metastasis. We found no protective or risk factors for tumor progression, and that almost half of all patients who underwent delayed surgery did so for reasons other than tumor progression. While not biopsying small (<1 cm) or very low suspicious nodules is already recommended, AS may be an appropriate treatment option in patients appropriately counseled, considering the low risk of advanced tumor progression but also the considerable patient population who fail to adhere to treatment. Alternatively, in aim of preventing overtreatment in patients who would rather take proactive measures against their low-risk carcinoma, minimally-invasive ablation techniques may be an attractive option.

Osseous Metastases in Thyroid Cancer: Unveiling Risk Factors, Disease Outcomes, and Treatment Impact.

Bone is the second most common site of metastasis in patients with thyroid cancer (TC) and dramatically impacts overall survival and quality of life with no definitive cure, yet there is no extensive study of the demographic and clinical risk factors in the recent literature. Data regarding 120,754 TC patients with bone metastasis were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate analyses were used to identify the risk factors of bone metastasis occurring in various histologies of TC. Cox regression was performed to analyze the influence of bone metastasis on overall survival. Hazard ratios were computed to analyze the association between bone metastasis and the primary outcomes. Of the 120,754 records collected from the SEER database from 2000 to 2019, 976 (0.8%) presented with bone metastasis, with occurrence being the greatest in patients of age ≥ 55 years (OR = 5.63, 95%CI = 4.72-6.71), males (OR = 2.60, 95%CI = 2.27-2.97), Blacks (OR = 2.38, 95%CI = 1.95-2.9) and Asian or Pacific Islanders (OR = 1.90, 95%CI = 1.58-2.27), and single marital status. TC patients presenting with bone metastasis (HR = 2.78, 95%CI = 2.34-3.3) or concurrent bone and brain metastases (HR = 1.62, 95%CI = 1.03-2.55) had a higher mortality risk. Older age, gender, race, and single marital status were associated with bone metastasis and poorer prognosis in TC patients at initial diagnosis. Understanding such risk factors can potentially assist clinicians in making early diagnoses and personalized treatment plans, as well as researchers in developing more therapeutic protocols.