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Endocrine May 2024The occurrence and histopathological features of incidental thyroid carcinoma (ITC) vary considerably among populations from different geographical regions. The aim of...
PURPOSE
The occurrence and histopathological features of incidental thyroid carcinoma (ITC) vary considerably among populations from different geographical regions. The aim of this study is to assess the prevalence and histopathological characteristics of ITC in patients who underwent thyroid surgery for apparently benign thyroid diseases in an endemic goiter area in Italy.
METHODS
A total of 649 consecutive patients (531 females and 118 males; mean age, 52.9 ± 11.0 years), who underwent thyroid surgery at the Endocrine Surgery Unit of the tertiary care "Renato Dulbecco" University Hospital (Catanzaro, Italy) in the period between years 2017 and 2022, were included in this retrospective study. A comprehensive histopathological examination was performed on surgically excised thyroid tissue. Logistic regression analysis was employed to identify potential predictors of ITC.
RESULTS
The histopathological examination revealed the presence of ITC in 81 patients, accounting for 12.5% of the total study population. The female to male ratio was found to be 6.4 to 1. Among the patients with ITC, 72 had papillary carcinoma (PTC), with 53 of these tumors being microcarcinomas (microPTC). Additionally, 5 patients had follicular thyroid carcinoma, 2 patients had low-risk follicular cell-derived thyroid neoplasms, 1 patient had an oncocytic carcinoma, and 1 patient had a medullary thyroid carcinoma. Logistic regression analysis demonstrated a significant association between female sex and incidental microPTC.
CONCLUSIONS
These findings provide further evidence of the common occurrence of ITC, typically in the form of microPTC, among individuals who undergo thyroid surgery for apparently benign thyroid diseases.
Topics: Humans; Female; Male; Thyroid Neoplasms; Middle Aged; Italy; Adult; Retrospective Studies; Incidental Findings; Aged; Goiter, Endemic; Prevalence; Thyroidectomy; Thyroid Gland; Adenocarcinoma, Follicular
PubMed: 38217773
DOI: 10.1007/s12020-023-03659-2 -
The Oncologist Apr 2024Mixed response (MR), a scenario featuring discordant tumor changes, has been reported primarily with targeted therapies or immunotherapy. We determined the incidence and...
BACKGROUND
Mixed response (MR), a scenario featuring discordant tumor changes, has been reported primarily with targeted therapies or immunotherapy. We determined the incidence and prognostic significance of MR in advanced non-small cell lung cancer (NSCLC) treated with cytotoxic chemotherapy.
PATIENTS AND METHODS
We analyzed patient-level data from ECOG-ACRIN E5508 (carboplatin-paclitaxel + bevacizumab induction followed by randomization to maintenance therapy regimens). For patients with at least 2 target lesions and available measurements after cycle 2, we characterized response as homogeneous response (HR, similar behavior of all lesions), MR (similar behavior but >30% difference in magnitude of best and least responding lesions), or true mixed response (TMR, best and least responding lesions showing different behavior: ≥10% growth versus ≥10% shrinkage). We compared category characteristics using Mann-Whitney U and Chi-square tests, and overall survival (OS) using log-rank test and Cox models.
RESULTS
Among 965 evaluable patients, HR occurred in 609 patients (63%), MR in 208 (22%), and TMR in 148 (15%). Median OS was 13.6 months for HR, 12.0 months for MR, and 7.6 months for TMR (P < .001). Compared to HR, TMR had inferior OS among stable disease cases (HR 1.62; 95% CI, 1.23-2.12; P < .001) and a trend toward inferior OS among progressive disease cases (HR 1.39; 95% CI, 0.83-2.33; P = .2). In multivariate analysis, TMR was associated with worse OS (HR 1.48; 95% CI, 1.22-1.79; P < .001).
CONCLUSION
True mixed response occurs in a substantial minority of lung cancer cases treated with chemotherapy and independently confers poor prognosis.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Prognosis; Incidence; Proportional Hazards Models; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Paclitaxel
PubMed: 38207008
DOI: 10.1093/oncolo/oyad335 -
Cureus Nov 2023Urogenital malignancies, encompassing urinary bladder cancer, prostate cancer, and renal cell carcinoma, pose significant diagnostic challenges due to overlapping...
BACKGROUND
Urogenital malignancies, encompassing urinary bladder cancer, prostate cancer, and renal cell carcinoma, pose significant diagnostic challenges due to overlapping histopathological features. GATA binding protein 3 (GATA3), a transcription factor associated with urothelial tissue, has shown promise as a potential diagnostic marker. This study aimed to investigate the incidence of these malignancies, explore GATA3's involvement in urothelial cancer (UC), and determine its role in distinguishing urogenital malignancies.
MATERIALS AND METHODS
A cross-sectional, retro-prospective, hospital-based study was conducted from May 2019 to April 2021. The surgical samples of patients who underwent transurethral resection of bladder tumour (TURBT), transurethral resection of the prostate (TURP), radical cystoprostatectomy, total and partial radical nephrectomy specimens during the study period were reviewed. Patients diagnosed with urinary bladder neoplasm and high-grade prostate neoplasm along with chromophobe, oncocytic, sarcomatoid variant and clear cell carcinoma, renal cell carcinoma were included. Immunohistochemical analysis of GATA3 expression was performed, with scoring based on nuclear staining intensity and percentage of tumor cells labeled.
RESULTS
The study included 64 patients, predominantly males over 60 years. Personal habits revealed a high prevalence of smoking (85.9%). The most prevalent symptom was hematuria (75.0%), followed by hematuria with urgency (20.3%). The most common site of lesion was posterolateral (31.3%). Urothelial cancer was the most common malignancy, primarily high-grade. Strong positive GATA3 expression was significantly associated with high-grade UC (p=0.01) and invasion (p=0.01). However, low-grade UC and papillary urothelial neoplasm of low malignant potential exhibited moderate GATA3 expression. GATA3 demonstrated potential for distinguishing UC from other histological types.
CONCLUSION
GATA3 expression correlates with high-grade urothelial cancer and invasive behavior, suggesting its utility as a diagnostic marker in challenging cases.
PubMed: 38161907
DOI: 10.7759/cureus.49635 -
Frontiers in Immunology 2023The roles of preexisting auto-reactive antibodies in immune-related adverse events (irAEs) associated with immune checkpoint inhibitor therapy are not well defined....
UNLABELLED
The roles of preexisting auto-reactive antibodies in immune-related adverse events (irAEs) associated with immune checkpoint inhibitor therapy are not well defined. Here, we analyzed plasma samples longitudinally collected at predefined time points and at the time of irAEs from 58 patients with immunotherapy naïve metastatic non-small cell lung cancer treated on clinical protocol with ipilimumab and nivolumab. We used a proteomic microarray system capable of assaying antibody reactivity for IgG and IgM fractions against 120 antigens for systemically evaluating the correlations between auto-reactive antibodies and certain organ-specific irAEs. We found that distinct patterns of auto-reactive antibodies at baseline were associated with the subsequent development of organ-specific irAEs. Notably, ACHRG IgM was associated with pneumonitis, anti-cytokeratin 19 IgM with dermatitis, and anti-thyroglobulin IgG with hepatitis. These antibodies merit further investigation as potential biomarkers for identifying high-risk populations for irAEs and/or monitoring irAEs during immunotherapy treatment.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT03391869.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Proteomics; Immune System Diseases; Immunoglobulin G; Immunoglobulin M
PubMed: 38152395
DOI: 10.3389/fimmu.2023.1322818 -
Beijing Da Xue Xue Bao. Yi Xue Ban =... Dec 2023To investigate the coagulation function indicators and identify influence factors of hypercoagulability in patients with adrenocorticotropic hormone (ACTH) independent...
OBJECTIVE
To investigate the coagulation function indicators and identify influence factors of hypercoagulability in patients with adrenocorticotropic hormone (ACTH) independent Cushing syndrome (CS).
METHODS
In our retrospective study, the electronic medical records system of Peking University First Hospital was searched for the patients diagnosed with ACTH independent CS on discharge from January 2014 to June 2019. Nonfunctional adrenal adenoma patients were chosen as control group and matched 1 ∶1 by body mass index (BMI), gender, and discharge date. Clinical features and coagulation function indicators were compared between the two groups.
RESULTS
In the study, 171 patients were included in each group. Compared with control group, activated partial thromboplastin time (APTT), and prothrombin time (PT) in ACTH independent CS group were significantly lower [(29.22±3.39) s . (31.86±3.63) s, < 0.001; (29.22±3.39) s . (31.86±3.63) s, < 0.001], and both D-dimer and fibrin degradation products (FDP) levels were significantly higher ( < 0.05). Percentage of APTT levels under the lower limit of reference range in the CS patients was significantly higher than that in nonfunctional group (21.6% . 3.5%, < 0.001). Percentage of D-dimer levels over the upper limit of reference range in the CS patients was significantly higher than that in nonfunctional group (13.5% . 6.6%, =0.041). There were three patients with deep venous thrombosis and one patient with pulmonary embolism in CS group, however none was in control group. The area under curve (AUC) of serum cortisol rhythm (8:00, 16:00 and 24:00) levels was negatively associated with the levels of PT (=-0.315, < 0.001) and APTT (=-0.410, < 0.001), and positively associated with FDP (=0.303, < 0.001) and D-dimer levels (=0.258, < 0.001). There were no differences in coagulation function indicators among different histopathologic subgroups (adrenocortical adenoma, adrenocortical hyperplasia, oncocytic adenoma, adrenocortical carcinoma). With Logistic regression analysis, the AUC of cortisol and glycosylated hemoglobin A1c (HbA1c) levels were independent risk factors for hypercoagulability in the ACTH independent CS patients ( < 0.05).
CONCLUSION
ACTH independent CS patients were more likely in hypercoagulable state compared with nonfunctional adrenal adenoma, especially in ACTH independent CS patients with higher levels of cortisol AUC and HbA1c. These patients should be paid attention to for the hypercoagulability and thrombosis risk.
Topics: Humans; Cushing Syndrome; Adrenocortical Adenoma; Adrenocorticotropic Hormone; Hydrocortisone; Retrospective Studies; Glycated Hemoglobin; Adrenal Cortex Neoplasms; Adenoma; Thrombophilia
PubMed: 38101790
DOI: 10.19723/j.issn.1671-167X.2023.06.017 -
JAMA Oncology Feb 2024Agents targeting programmed death ligand 1 (PD-L1) have demonstrated efficacy in triple-negative breast cancer (TNBC) when combined with chemotherapy and are now the...
Atezolizumab in Combination With Carboplatin and Survival Outcomes in Patients With Metastatic Triple-Negative Breast Cancer: The TBCRC 043 Phase 2 Randomized Clinical Trial.
IMPORTANCE
Agents targeting programmed death ligand 1 (PD-L1) have demonstrated efficacy in triple-negative breast cancer (TNBC) when combined with chemotherapy and are now the standard of care in patients with PD-L1-positive metastatic disease. In contrast to microtubule-targeting agents, the effect of combining platinum compounds with programmed cell death 1 (PD-1)/PD-L1 immunotherapy has not been extensively determined.
OBJECTIVE
To evaluate the efficacy of atezolizumab with carboplatin in patients with metastatic TNBC.
DESIGN, SETTING, AND PARTICIPANTS
This phase 2 randomized clinical trial was conducted in 6 centers from August 2017 to June 2021.
INTERVENTIONS
Patients with metastatic TNBC were randomized to receive carboplatin area under the curve (AUC) 6 alone or with atezolizumab, 1200 mg, every 3 weeks until disease progression or unacceptable toxic effects with a 3-year duration of follow-up.
MAIN OUTCOME AND MEASURES
The primary end point was investigator-assessed progression-free survival (PFS). Secondary end points included overall response rate (ORR), clinical benefit rate (CBR), and overall survival (OS). Other objectives included correlation of response with tumor PD-L1 levels, tumor-infiltrating lymphocytes (TILs), tumor DNA- and RNA-sequenced biomarkers, TNBC subtyping, and multiplex analyses of immune markers.
RESULTS
All 106 patients with metastatic TNBC who were enrolled were female with a mean (range) age of 55 (27-79) years, of which 12 (19%) identified as African American/Black, 1 (1%) as Asian, 73 (69%) as White, and 11 (10%) as unknown. Patients were randomized and received either carboplatin (n = 50) or carboplatin and atezolizumab (n = 56). The combination improved PFS (hazard ratio [HR], 0.66; 95% CI, 0.44-1.01; P = .05) from a median of 2.2 to 4.1 months, increased ORR from 8.0% (95% CI, 3.2%-18.8%) to 30.4% (95% CI, 19.9%-43.3%), increased CBR at 6 months from 18.0% (95% CI, 9.8%-30.1%) to 37.5% (95% CI, 26.0%-50.6%), and improved OS (HR, 0.60; 95% CI, 0.37-0.96; P = .03) from a median of 8.6 to 12.6 months. Subgroup analysis showed PD-L1-positive tumors did not benefit more from adding atezolizumab (HR, 0.62; 95% CI, 0.23-1.65; P = .35). Patients with high TILs (HR, 0.12; 95% CI, 0.30-0.50), high mutation burden (HR, 0.50; 95% CI, 0.23-1.06), and prior chemotherapy (HR, 0.59; 95% CI, 0.36-0.95) received greater benefit on the combination. Patients with obesity and patients with more than 125 mg/dL on-treatment blood glucose levels were associated with better PFS (HR, 0.35; 95% CI, 0.10-1.80) on the combination. TNBC subtypes benefited from adding atezolizumab, except the luminal androgen receptor subtype.
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial, the addition of atezolizumab to carboplatin significantly improved survival of patients with metastatic TNBC regardless of PD-L1 status. Further, lower risk of disease progression was associated with increased TILs, higher mutation burden, obesity, and uncontrolled blood glucose levels.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03206203.
Topics: Humans; Female; Middle Aged; Aged; Male; Carboplatin; Triple Negative Breast Neoplasms; B7-H1 Antigen; Blood Glucose; Ligands; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Disease Progression; Obesity; Apoptosis; Antibodies, Monoclonal, Humanized
PubMed: 38095878
DOI: 10.1001/jamaoncol.2023.5424 -
Cureus Nov 2023Papillary thyroid carcinoma is the most common type of thyroid carcinoma, diagnosed on the basis of a predefined set of distinctive nuclear features. There are about 15...
Papillary thyroid carcinoma is the most common type of thyroid carcinoma, diagnosed on the basis of a predefined set of distinctive nuclear features. There are about 15 known variants of papillary thyroid carcinoma, and the oncocytic variant is not one of the commonly encountered prototypic conventional papillary thyroid carcinoma. We hereby report an unusual case of a 48-year-old woman presenting with thyroid swelling, which proved to be a diagnostic crisis.
PubMed: 38073932
DOI: 10.7759/cureus.48425 -
Thyroid : Official Journal of the... Mar 2024Lenvatinib and sorafenib are standard of care first-line treatments for advanced, radioiodine-refractory (RAIR) differentiated thyroid cancer (DTC). However, most... (Randomized Controlled Trial)
Randomized Controlled Trial
Increased Progression-Free Survival with Cabozantinib Versus Placebo in Patients with Radioiodine-Refractory Differentiated Thyroid Cancer Irrespective of Prior Vascular Endothelial Growth Factor Receptor-Targeted Therapy and Tumor Histology: A Subgroup Analysis of the COSMIC-311 Study.
Lenvatinib and sorafenib are standard of care first-line treatments for advanced, radioiodine-refractory (RAIR) differentiated thyroid cancer (DTC). However, most patients eventually become treatment-resistant and require additional therapies. The phase 3 COSMIC-311 study investigated cabozantinib in patients with RAIR DTC who progressed on lenvatinib, sorafenib, or both and showed that cabozantinib provided substantial clinical benefit. Presented in this study is an analysis of COSMIC-311 based on prior therapy and histology. Patients were randomized 2:1 (stratification: prior lenvatinib [yes/no]; age [≤65, >65 years]) to oral cabozantinib (60 mg tablet/day) or matched placebo. Eligible patients received 1-2 prior vascular endothelial growth factor receptor-targeting tyrosine kinase inhibitors for DTC (lenvatinib or sorafenib required), had a confirmed DTC diagnosis, and were refractory to or ineligible for radioiodine therapy. For this analysis, progression-free survival (PFS) and objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 by a blinded independent radiology committee were evaluated by prior therapy (lenvatinib only, sorafenib only, both) and histology (papillary, follicular, oncocytic, poorly differentiated). Two hundred fifty-eight patients were randomized (170 cabozantinib/88 placebo) who previously received sorafenib only ( = 96), lenvatinib only ( = 102), or both ( = 60). The median follow-up was 10.1 months. The median PFS (months) with cabozantinib/placebo was 16.6/3.2 (sorafenib only: hazard ratio [HR] 0.13 [95% confidence interval, CI, 0.06-0.26]), 5.8/1.9 (lenvatinib only: HR 0.28 [95% CI 0.16-0.48]), and 7.6/1.9 (both: HR 0.27 [95% CI 0.13-0.54]). The ORR with cabozantinib/placebo was 21%/0% (sorafenib only), 4%/0% (lenvatinib only), and 8%/0% (both). Disease histology consisted of 150 papillary and 113 follicular, including 43 oncocytic and 36 poorly differentiated. The median PFS (months) with cabozantinib/placebo was 9.2/1.9 (papillary: HR 0.27 [95% CI 0.17-0.43]), 11.2/2.5 (follicular: HR 0.18 [95% CI 0.10-0.31]), 11.2/2.5 (oncocytic: HR 0.06 [95% CI 0.02-0.21]), and 7.4/1.8 (poorly differentiated: HR 0.18 [95% CI 0.08-0.43]). The ORR with cabozantinib/placebo was 15%/0% (papillary), 8%/0% (follicular), 11%/0% (oncocytic), and 9%/0% (poorly differentiated). Safety outcomes evaluated were consistent with those previously observed for the overall population. Results indicate that cabozantinib benefits patients with RAIR DTC, regardless of prior lenvatinib or sorafenib treatments or histology. NCT03690388.
Topics: Humans; Aged; Sorafenib; Progression-Free Survival; Iodine Radioisotopes; Vascular Endothelial Growth Factor A; Antineoplastic Agents; Thyroid Neoplasms; Phenylurea Compounds; Quinolines; Receptors, Vascular Endothelial Growth Factor; Adenocarcinoma; Protein Kinase Inhibitors; Anilides; Pyridines
PubMed: 38062732
DOI: 10.1089/thy.2023.0463 -
Journal of Medical Case Reports Dec 2023Cancer antigen 15-3 is a protein that clinicians commonly measure to monitor outcomes and response to treatment in patients with breast cancer. However, cancer antigen...
BACKGROUND
Cancer antigen 15-3 is a protein that clinicians commonly measure to monitor outcomes and response to treatment in patients with breast cancer. However, cancer antigen 15-3 can also be elevated in other, benign and malignant conditions.
CASE PRESENTATION
A 73-year-old White woman with history of breast cancer presented to her primary care physician with right hip pain, and laboratory testing revealed elevated cancer antigen 15-3. Further workup with radiographic imaging revealed a large mass in her right kidney. The renal mass was subsequently removed, and the cancer antigen 15-3 level returned to normal.
CONCLUSIONS
Elevation of cancer antigen 15-3 owing to causes other than breast cancer recurrence can be a potential diagnostic pitfall during a patient's follow-up. It is important for clinicians to be aware of the limitations of cancer markers and to utilize a combination of diagnostic tests for patient evaluation.
Topics: Female; Humans; Aged; Breast Neoplasms; Kidney; Kidney Neoplasms
PubMed: 38062521
DOI: 10.1186/s13256-023-04088-5 -
CytoJournal 2023Papillary renal neoplasm with reverse nuclear polarity (PRNRP) is an emerging oncocytic renal tumor. Cytomorphologic features of this tumor have not been described in...
Papillary renal neoplasm with reverse nuclear polarity (PRNRP) is an emerging oncocytic renal tumor. Cytomorphologic features of this tumor have not been described in the literature before. The objective of this study was to review the cytomorphology of a case PRNRP and compare with cytomorphologic features of papillary renal cell carcinomas (pRCCs) reported in the literature. 1 case of core needle biopsy (CNB) with touch preparation (TP) of a renal mass diagnosed as PRNRP was reviewed retrospectively. Clinical presentation, cytomorphologic features, ancillary tests and histopathology results were analyzed. The touch preparation was cellular and showed tight 3-D clusters of cuboidal epithelial cells with variable presence of fibrovascular cores (FC), granular eosinophilic cytoplasm, round apically located grade 1 nuclei compared to cases of pRCC that consistently showed presence of FCs lined by cuboidal to columnar epithelial cells with variable degree of cytologic atypia. Features characteristic of pRCC like foamy macrophages, hemosiderin laden macrophages, nuclear grooves or psammoma bodies were not present. No necrosis or mitosis were identified. By immunohistochemistry (IHC) the tumor cells were positive for cytokeratin 7, GATA-3 and AMACR (focal) and negative for CA-IX, CD117 and vimentin. Cytomorphologic features of PRNRP are unique and characterized by tight 3-D clusters (with or without FCs) of cuboidal cells with small round apically located nuclei and finely granular oncocytic cytoplasm. Specific diagnosis of PRNRP on cytology or CNB is feasible along with use of ancillary tests IHC and /or molecular tests.
PubMed: 38053633
DOI: 10.25259/Cytojournal_9_2023