Radioactive iodine therapy for thyroid cancer coexisting with hashimoto's thyroiditis: a systematic review and meta-analysis.

OBJECTIVES: To investigate the clinical character of differentiated thyroid cancer (DTC) coexisting with Hashimoto's thyroiditis (HT) and provide state-of-art evidence for personalized RAIT for patients coexisting with HT. METHODS: From January 2000 to January 2023, PubMed, Embase, Web of Science databases were searched for relevant original articles that published in English on the RAIT efficacy for DTC with HT. Revman 5.4 and Stata 17.0 were used for date analysis. RESULTS: Eleven studies involved 16,605 DTC patients (3,321 with HT) were included. HT were more frequent in female (OR: 2.90, 95% CI: 1.77 to 4.76, P < 0.00001). The size of tumor (MD: -0.20, 95% CI: -0.30 to -0.11), extrathyroidal extension rate (OR: 0.77, 95% CI: 0.67 to 0.90) and metastasis rate (OR: 0.18, 95% CI: 0.08 to 0.41) were less in HT, but TNM stage had no significant difference among HT and non-HT group. DFS rate (OR: 1.96, 95% CI : 1.57 to 2.44, P < 0.00001), 5-year and 10-year DFS (OR: 1.73, 95% CI: 1.04 to 2.89, P = 0.04; OR: 1.56, 95% CI: 1.17 to 2.09, P = 0.003, respectively) were higher in HT group. The recurrent (OR: 0.62, 95% CI: 0.45 to 0.83, P = 0.002), RAIT dosage (MD=-38.71, 95% CI: -60.86 to -16.56, P = 0.0006) and treatment (MD: -0.13, 95% CI: -0.22 to -0.03, P = 0.008) were less in HT group. CONCLUSIONS: DTC coexisting with HT was associated with less invasion. DFS of HT group was higher than non-HT group after RAIT. Low dose treatment did not impair the efficacy of RAIT in DTC with HT. ADVANCES IN KNOWLEDGE: Hashimoto's thyroiditis is a risk for DTC, but it minimalizes the progression of cancer and enhance the efficacy of RAIT, which should be considered in personalizing RAIT.

Predictive value of monocyte to high-density lipoprotein cholesterol ratio and tumor markers in colorectal cancer and their relationship with clinicopathological characteristics.

OBJECTIVE: To evaluate the predictive value of monocyte (M) to high-density lipoprotein cholesterol (HDL-C) ratio (MHR) and tumor markers in colorectal cancer (CRC) and their correlation with clinicopathological characteristics. METHODS: Hematology test data and medical records of 202 CRC patients and 201 healthy subjects were collected retrospectively. The diagnostic efficacy of MHR was evaluated using receiver operating characteristic (ROC) curves and risk factors for CRC were analyzed by multivariate logistic regression. RESULTS: CRC patients had significantly higher M, MHR, carcinoembryonic antigen (CEA), and carbohydrate antigen 199 (CA199) levels, but significantly lower HDL-C levels than healthy controls (all P < 0.05). Additionally, MHR was positively correlated with tumor differentiation in CRC patients (P = 0.049); CEA and CA199 levels in CRC patients increased with increased stage, lymph node metastasis and tumor size ≥ 5 cm (all P < 0.05). Furthermore, high levels of MHR, CA199 and CEA were independent risk factors for CRC. The area under ROC curve of MHR combined with CEA and CA199 was 0.882/0.869 for the diagnosis of CRC, respectively. CONCLUSION: This is the first study to explore the predictive value of MHR in CRC, and its continuous increase is an independent risk factor for CRC. MHR is a promising predictor for CRC progression along with CA199 and CEA.

Possibility analysis of thyroid imaging parameters for dose adjustment in 131I treatment of hyperthyroidism.

BACKGROUND: To determine the thyroid uptake rate by correcting the background and analyze its clinical significance. METHODS: The study included 161 patients with hyperthyroidism. The thyroid uptake rate was calculated by drawing a 100 pixels ROI (region of interest) background, above and below the thyroid and correcting the thyroid ROI for background counting. At the same time, the clinical baseline characteristic parameters such as age and thyroid volume etc. of patients with hyperthyroidism were collected. The consistency of 99mTcO4uptake rate before treatment and 131I-uptake rate after treatment, and the correlation between uptake rate of thyroid and baseline characteristic parameters were also analyzed. RESULTS: The uptake rate of 99mTcO4 was found positively correlated with 3 h-radioactive iodine uptake (RAIU), 24 h-RAIU, 3 h/24 h conversion rate, thyroid volume, 131I activity free triiodothyronine (FT3) and free thyroxine (FT4), and showed negative correlation with age, effective half-life (P<0.05). The uptake rate of 131I was found positively correlated with 3 h-RAIU, 24 h-RAIU, 3 h/24 h conversion rate, thyroid volume, 131I activity, FT3, FT4 (P<0.05). In patients with positive thyrotrophin receptor antibody (TRAb), a significant positive correlation between uptake rate of 99mTcO4 and 131I (P<0.05) was observed. There was a high consistency between pretreatment uptake rate of 99mTcO4 and post-treatment uptake rate of 131I (P=0.009; W=0.7). CONCLUSIONS: The corrected thyroid uptake rate is remarkably correlated with clinical characteristic parameters of patients, which can be used to comprehensively evaluate the comprehensive condition of patients with hyperthyroidism.

Relationship between certain hematological parameters and risk of breast cancer.

Aim: To explore the association between preoperative hemoglobin-to-red cell distribution width ratio (HRR), platelet-to-monocyte ratio or monocyte-to-high-density lipoprotein ratio and risk of breast cancer. Materials & methods: The clinical data of 226 patients with breast cancer were retrospectively analyzed and compared with 199 healthy controls by multivariate logistic regression analysis. Results: Multivariate logistic regression analysis revealed that HRR (p < 0.001) and monocyte-to-high-density lipoprotein ratio (p < 0.001) were independent predictors of breast cancer and lower HRR was associated with longer hospitalization, larger red cell distribution width value and lower hemoglobin level (p < 0.05). Conclusion: A significant association was found between HRR and clinical characteristics in breast cancer patients. Therefore, HRR is expected to become a novel and promising predictor of breast cancer.

Breast cancer is a common cancer, accounting for approximately 30% of all new cases of cancer diagnosed in women. It is also one of the main causes of cancer-related death in women. Clinically, breast cancer screening and early diagnosis rely mainly on mammography, ultrasound imaging, etc., but these tests are expensive and complex and are not suitable for early screening of breast cancer. This study found that low hemoglobin-to-red cell distribution width ratio and high monocyte-to-high-density lipoprotein ratio were associated with increased breast cancer risk. Because the determination of hemoglobin-to-red cell distribution width ratio and monocyte-to-high-density lipoprotein ratio is relatively simple, economic and convenient, regular detection of related markers can provide valuable information for early detection of breast cancer.

Leucine zipper downregulated in cancer 1 may serve as a favorable prognostic biomarker by influencing proliferation, colony formation, cell cycle, apoptosis, and migration ability in hepatocellular carcinoma.

Aims: Leucine zipper downregulated in cancer 1 (LDOC1) inhibits tumor growth in several cancers. However, the expression and function of LDOC1 in hepatocellular carcinoma (HCC) remain unknown. In this study, we aimed to investigate how LDOC1 influenced tumor progression and the biological functions of HCC. Methods: The transcription levels of LDOC1 were determined using the GEPIA and UALCAN online databases and a real-time polymerase chain reaction. Western blot and immunohistochemistry were used to validate the protein levels of LDOC1. The online Kaplan-Meier Plotter was applied for survival analysis. Then lentivirus transfection was used to construct LDOC1 exogenous overexpression cell lines. Proliferation, clone formation, cell cycle, apoptosis, and migration assays were performed with the LDOC1-upregulated Huh7 and Hep3B cell lines. The phosphorylated and total levels of AKT and mTOR were determined using a Western blot to explore the potential molecular mechanism of LDOC1. Results: In the GEPIA and UALCAN analyses, LDOC1 was lowly expressed in tumors, had high expression in normal tissue samples (p < 0.05), and negatively correlated with tumor grade progression. The down-regulation of LDOC1 in HCC was validated with real-time polymerase chain reaction, Western blot, and immunohistochemistry (all p < 0.05). LDOC1 transcription levels were negatively associated with overall, progression-free, recurrence-free, and disease-specific survival (all p < 0.05). The functional experiments suggested that the overexpression of LDOC1 contributed to increased G1 and G2 stages in Huh7, while increased G2 stage in Hep3B, and decreased cell proliferation, clone formation, and migration, as well as increased the apoptosis rate compared with the control group (all p < 0.05). Furthermore, LDOC1 up-regulation reduced the p-AKT/AKT and p-mTOR/mTOR, which indicates an inactivation of the AKT/mTOR pathway. Conclusion: The tumor-suppressor LDOC1 varied in HCC and non-HCC tissues, which can serve as a candidate prognostic biomarker. LDOC1 influenced survival by affecting proliferation, colony formation, cell cycle, apoptosis, and migration ability, which might be attributed to the AKT/mTOR inhibition in HCC.

The Role of CXC Chemokines in Cancer Progression.

CXC chemokines are small chemotactic and secreted cytokines. Studies have shown that CXC chemokines are dysregulated in multiple types of cancer and are closely correlated with tumor progression. The CXC chemokine family has a dual function in tumor development, either tumor-promoting or tumor-suppressive depending on the context of cellular signaling. Recent evidence highlights the pro-tumorigenic properties of CXC chemokines in most human cancers. CXC chemokines were found to play pivotal roles in promoting angiogenesis, stimulating inflammatory responses, and facilitating tumor metastases. Enhanced expression of CXC chemokines is always signatured with inferior survival and prognosis. The levels of CXC chemokines in cancer patients are in dynamic change according to the tumor contexts (e.g., chemotherapy resistance and tumor recurrence after surgery). Thus, CXC chemokines have great potential to be used as diagnostic and prognostic biomarkers and therapeutic targets. Currently, the molecular mechanisms underlying the effect of CXC chemokines on tumor inflammation and metastasis remain unclear and application of antagonists and neutralizing antibodies of CXC chemokines signaling for cancer therapy is still not fully established. This article will review the roles of CXC chemokines in promoting tumorigenesis and progression and address the future research directions of CXC chemokines for cancer treatment.

Ectopic Pulmonary Goiter Simulating Malignant Tumor Detected on SPECT/CT.

ABSTRACT: A 46-year-old asymptomatic woman with a newly detected large pulmonary mass was admitted to our hospital. An ultrasonography-guided needle biopsy was performed based on a suspicion of malignancy, and an ectopic goiter was confirmed pathologically. Laboratory findings were unremarkable, except that thyroid function tests suggested subclinical hyperthyroidism. A 131I whole-body scintigraphy and SPECT/CT were further performed and revealed intense radioiodine uptake in the pulmonary mass, the mediastinal nodule, and thyroid gland. A diagnosis of ectopic pulmonary goiter with normally located thyroid was finally made.

Salivary gland function in women with Hashimoto's thyroiditis without xerostomia and the correlation with auto-thyroid antibodies.

BACKGROUND: Hashimoto's thyroiditis (HT) may cause salivary dysfunction in patients resulting in xerostomia, but little is known about changes in salivary function in patients with no obvious dry mouth symptoms. In this study we assessed salivary function in women with HT, who had not experienced xerostomia and, for the first time, evaluated the effects of thyroid auto-antibodies on this function.: METHODS: Sixty consecutive subjects were included, comprising 32 women (mean age, 36 ±â€Š12 years) diagnosed with HT accompanied by differentiated thyroid cancer (DTC) in the study group (HT group), along with a control group (DTC group) of 28 women (mean age, 40 ±â€Š12 years) diagnosed with DTC only. Salivary gland scintigraphy was used to assess salivary function with the semi-quantitative parameters of maximum absorption ratio and maximum secretion ratio, the decrease of which indicate impaired salivary function. Moreover, the HT and DTC groups were divided into four subgroups (Anti- HT, Anti+ HT, Anti- DTC, and Anti+ DTC), based on the presence of anti-thyroid peroxidase antibody (TPOAb) and anti-thyroglobulin antibody (TgAb). Finally, salivary gland semi-quantitative parameters were correlated with levels of thyroid-stimulating hormone (TSH), TGAb, and TPOAb in the HT and DTC groups. RESULTS: None of the semi-quantitative parameters examined in parotid or submandibular glands differed significantly between the HT and DTC groups. However, the maximum secretion ratio for the parotid and submandibular glands were significantly different in the subgroup comparison (p < 0.05). Furthermore, the TgAb, TPOAb, and TSH values correlated significantly with salivary excretive function (p ≤ 0.05). CONCLUSION: Women with HT without xerostomia may not have salivary functional impairment during hypothyroidism. Serum thyroid autoantibody and TSH levels may mainly influence salivary excretive function but not uptake function.

Immunohistochemical basigin expression level in thyroid cancer tissues.

BACKGROUND: Thyroid cancer (TC) is the most common endocrine malignancy; basigin (also known as BSG) plays a crucial role in tumor cell invasion, metastasis, and angiogenesis. This study was designed to identify the change of BSG expression in TC and its possible potential mechanism. METHODS: The BSG expression levels in TC were demonstrated using data collected from in-house immunohistochemical (IHC), RNA-sequencing (RNA-seq), microarrays, and literatures. Integrated analysis was performed to determined BSG expression levels in TC comprehensively. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed with the integration of BSG co-expressed genes and differentially expressed genes (DEGs) in TC tissues to explore the potential mechanisms of BSG in TC. RESULTS: The protein expression level of BSG was significantly higher in TC cases based on the IHC experiments. In addition, the combined SMD for BSG expression was 0.39 (p < 0.0001), the diagnostic odds ratio was 3.69, and the AUC of the sROC curve was 0.6986 using 1182 TC cases and 437 non-cancerous cases from 17 independent datasets. Furthermore, BSG co-expressed genes tended to be enriched in gene terms of the extracellular matrix (ECM), cell adhesion, and cell-cell interactions. The expression levels of nine hub BSG co-expressed genes were markedly upregulated in TC cases. CONCLUSION: BSG expression levels were closely correlated with the progression of TC and may affect the signals of the ECM, cell adhesion, and cell-cell interactions.

A two-way comparison of whole-body 18FDG PET-CT and whole-body contrast-enhanced MRI for distant metastasis staging in patients with malignant tumors: a meta-analysis of 13 prospective studies.

BACKGROUND: The correct staging of distant metastasis is crucial in deciding an adequate course of therapy for cancer patients. This meta-analysis was carried out to produce an evaluation and comparison of the performances of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18FDG PET-CT) and contrastenhanced magnetic resonance imaging (MRI) in detecting distant metastasis in patients suffering malignant tumors. Systematic literature searches of the MEDLINE and Embase databases were conducted to identify relevant studies in the period from December 31, 1950 to August 1, 2019. We used the following search terms: MRI, magnetic resonance imaging, PET, positron emission tomography, staging, distant metastasis, and distant recurrence. The searches were carried out by two independent reviewers. We only included relevant studies that evaluated both 18FDG PET-CT and contrast-enhanced MRI in relation to distant metastasis detection in the same patients with malignant tumors. The two reviewers independently extracted relevant data from the eligible studies, and the quality of each study was determined with "Quality Assessment of Diagnostic Accuracy Studies-2". Using the bivariate model, we obtained pooled estimates for sensitivity and specificity. The area under the curve (AUC) of summary receiver operating characteristic (SROC) curves for 18FDG PET-CT and contrast-enhanced MRI was used to extra and synthesize, respectively. METHODS: Pooled sensitivities and specificities, and the AUC of SROC curves for 18FDG PET-CT and contrast-enhanced MRI were used to measure the main outcomes, respectively. RESULTS: Across all 13 studies (1,465 patients), 18FDG PET-CT had similar sensitivity (0.84 vs. 0.85) and specificity (0.96 vs. 0.98) to contrast-enhanced MRI. In the 5 studies related to head and neck cancer (511 patients), 18FDG PET-CT had similar sensitivity (0.82 vs. 0.81) and specificity (0.97 vs. 0.98) to contrastenhanced MRI. In the 6 lung cancer-related studies (779 patients), sensitivity (0.72 vs. 0.85) and specificity (0.95 vs. 1.00) tended to be lower in 18FDG PET-CT than in contrast-enhanced MRI. CONCLUSIONS: :18FDG PET-CT and contrast-enhanced MRI both performed well as detectors of distant metastasis in the diagnosis of cancer patients. The subgroup analysis suggests that 18FDG PET-CT and contrast-enhanced MRI may possess different advantageous qualities for distant metastasis staging of patients with various types of tumor.

Clinical role of combining alpha-fetoprotein and lens culinaris agglutinin-reactive fraction of alpha-fetoprotein for hepatocellular carcinoma: Evidence from literature and an original study.

BACKGROUND: To evaluate the clinical diagnostic efficacy of the combination of alpha-fetoprotein (AFP) and lens culinaris agglutinin-reactive fraction of AFP/total AFP (AFP-L3%) for detecting hepatocellular carcinoma (HCC). METHODS: A comprehensive and systemic literature search was executed in Web of Science, PubMed, and the Cochrane Library websites. Then, the related articles were reviewed and the quality of included studies was evaluated with the QUADAS tool. Further, serum samples were collected from 49 HCC patients, 52 cirrhosis patients, 47 hepatitis patients, and 48 healthy controls and these samples were tested for AFP and AFP-L3% levels. RESULTS: A total of 16 eligible articles were included in our meta-analysis. The overall sensitivity (SEN) of AFP + AFP-L3% was higher than that of AFP or AFP-L3 alone; the overall specificity (SPE) of AFP + AFP-L3% was lower than that of AFP or AFP-L3 alone. In the original study, the related statistics were, respectively, SEN = 0.592 and SPE = 0.918 for AFP; SEN = 0.367 and SPE = 1.000 for AFP-L3%; and SEN = 0.592 and SPE = 0.918 for the combination. CONCLUSION: The results of meta-analysis indicate there is a beneficial effect of using the unity of AFP and AFP-L3% for HCC diagnosing. However, in the original study, just for the results of sensitivity and specificity, there is no significant difference between AFP alone and AFP + AFP-L3%.

A novel timesaving and semiquantitative method for radionuclide hepatobiliary scintigraphy for suspected biliary atresia.

BACKGROUND: To optimize the performance of the hepatobiliary scintigraphy (HS) for suspected biliary atresia (BA) using a timesaving and semiquantitative method without a loss in diagnostic accuracy. METHODS: A retrospective analysis of 185 patients with persistent jaundice who underwent surgery were included. According to the surgical evaluation and pathological diagnosis, patients were divided into a BA group (99 cases) and an infant hepatitis syndrome (IHS) group (86 cases). 99mTc-labeled diethylacetanilide-iminodiacetic acid (99mTc-EHIDA) HS was performed before surgery. The average intestinal radioactivity uptake value minus the background average of radioactivity uptake value at 6 h after label injection (abbreviated as 6-h I-B) was calculated and the difference in 6-h I-B between the two groups was evaluated. The difference in diagnostic efficacy between 6-h I-B and the conventional 24-h HS in BA was also evaluated. RESULTS: A significant difference in 6-h I-B between the two groups was found (t=-5.975, P<0.001) and a high level of efficacy of 6-h I-B in the diagnosis of BA was detected. The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of 6-h I-B in the diagnosis of BA were 87.88%, 47.67%, 69.19%, 65.91%, and 77.36% respectively, while the corresponding parameters of the 24-h hepatobiliary imaging were 90.91%, 36.05%, 65.41%, 62.07%, and 77.50% respectively, with no significant difference between these values in the diagnosis of BA. CONCLUSIONS: HS plays an important role in the diagnosis of infantile jaundice due to conjugated hyperbilirubinemia. The timesaving and semiquantitative method of the 6-h hepatobiliary static imaging showed the same high sensitivity and NPV of the conventional 24-h HS in preventing unnecessary surgery. In the setting of suspected BA, imaging resource utilization could be improved via reducing the acquisition time and simplifying the examination process. The 24-h delay in imaging was considered unnecessary because it was not significantly superior.

Identification of Serum Biomarkers for Ischemic Penumbra by iTRAQ-Based Quantitative Proteomics Analysis.

PURPOSE: Ischemic penumbra is the main therapeutic target for acute ischemic stroke. The aim in this study is to investigate the potential serum biomarkers of penumbra that could fulfill a complementary role in the acute stroke clinical decision-making process. EXPERIMENTAL DESIGN: An established focal cerebral ischemia model is applied in rats. Using isobaric tags for relative and absolute quantitation combined with liquid chromatography-tandem mass spectrometry, the global expression profiles of proteins in ischemic penumbra tissue and serum from rats subjected to different ischemic times are identified and quantified. Candidate biomarkers are screened out with bioinformatics analysis and further validated by western blotting. RESULTS: Herein, a total of 4568 proteins in the penumbra and 1915 proteins in the serum are identified. Two proteins related to the penumbra, RHOA, and CDC42, are screened out through an integrative analysis. The expression levels of RHOA and CDC42 in the penumbra and serum gradually increase synchronously with the prolonged ischemia time. CONCLUSIONS AND CLINICAL RELEVANCE: The study provides the results of a proteomic analysis to identify serum biomarkers of the penumbra. Upregulation of RHOA and CDC42 may be useful for the early assessment of ischemic penumbra and could serve as potential serum biomarkers.

The incidence and risk factors for central lymph node metastasis in cN0 papillary thyroid microcarcinoma: a meta-analysis.

Although there have been many studies identifying clinical and pathologic factors that may predict central lymph node metastases (CLNM) in papillary thyroid microcarcinoma (PTMC) patients without clinically cervical lymph node metastasis (cN0), the results were inconsistent. And whether prophylactic central lymph node dissection (pCLND) should be performed in cN0 PTMC remains controversial. The EMBASE, PubMed, MEDLINE and the Cochrane Library were searched until Oct 2015 to identify relevant studies. Primary outcomes were clinical and pathologic factors for CLNM. Secondary outcomes included CLNM rate, surgical complications of hypocalcaemia and recurrent laryngeal nerve(RLN) injury and neck recurrences. Statistical analysis was performed using Stata 12.0. Fourteen eligible studies enrolling 4573 patients were included in this meta-analysis. The overall incidence of CLNM was 33 % (95 % CI 29-37). An elevated risk of CLNM was significantly associated with male gender (OR 2.33, 95 % CI 1.71-3.17), age <45 years (OR 1.27, 95 % CI 1.08-1.48), tumor size >5 mm (OR 2.16, 95 % CI 1.87-2.50), multifocality (OR 1.73, 95 % CI 1.45-2.05), extrathyroidal extension (OR 1.99, 95 % CI 1.66-2.37) and lymphovascular invasion (OR 3.87, 95 % CI 1.64-9.10), but not with thyroid bilaterality (OR 1.41, 95 % CI 0.89-2.22) and chronic lymphocytic thyroiditis (OR 0.98, 95 % CI 0.66-1.47). The pooled frequency of permanent hypocalcaemia, permanent RLN injury and neck recurrences was 1.1, 0.5 and 2.8 %, respectively. cN0 PTMC patients have a considerable CLNM rate and have a low pooled incident of surgical complications and neck recurrences with pCLND. Six unfavorable clinical and pathologic factors, which were significantly associated with CLNM, were identified. These findings may help guide the application of pCLND or subsequent treatment in cN0 PTMC.