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At least 19 recordsLinked to original sources
PubMed2026

Transcriptome-based high-frequency recurrence index predicts frequent recurrence in non-muscle-invasive bladder cancer after Bacillus Calmette-Guérin therapy.

BACKGROUND: High-frequency recurrence (HfR,&#x2009;&#x2265;&#x2009;2 recurrences) in non-muscle-invasive bladder cancer (NMIBC) poses a significant clinical burden. Current risk models, such as the European Organization for Research and Treatment of Cancer (EORTC), the European Association of Urology (EAU), and the UROMOL classification, offer limited predictive accuracy for identifying patients at risk for frequent recurrence despite appropriate treatment. METHODS: A 75-gene high-frequency recurrence index (HfRI) was constructed by selecting recurrence-associated genes using differential expression and Cox regression analyses. The HfRI was computed as a weighted sum of normalized gene expression values. The model was trained on a discovery cohort and validated in multiple cohorts (n&#x2009;=&#x2009;1379) using machine-learning approaches. Clinical relevance was assessed using recurrence-free survival (RFS) and Cox models, and predictive performance was compared with that of the EORTC, EAU, and UROMOL classifications using the area under the curve (AUC) and the concordance index (c-index). RESULTS: The HfRI robustly stratified patients into high-risk and low-risk groups across six independent NMIBC cohorts. Patients classified as HfRI-high had a significantly greater likelihood of experiencing&#x2009;&#x2265;&#x2009;2 recurrences (&#x3c7;2, p&#x2009;=&#x2009;0.001) and showed markedly reduced RFS (log-rank test, p&#x2009;<&#x2009;0.001). The adverse prognostic effect of the HfRI persisted even among patients treated with BCG therapy (log-rank test, p&#x2009;=&#x2009;0.02). Multivariate analysis revealed that the HfRI was an independent predictor of HfR (HR&#x2009;=&#x2009;2.82, 95% CI&#x2009;=&#x2009;1.89-4.20, p&#x2009;<&#x2009;0.001). Compared with established clinical risk classifiers, the HfRI demonstrated superior predictive performance (AUC&#x2009;=&#x2009;0.736, c-index&#x2009;=&#x2009;0.673) in terms of the EORTC (AUC&#x2009;=&#x2009;0.594), EAU (AUC&#x2009;=&#x2009;0.557) risk groups, and UROMOL2021 (AUC&#x2009;=&#x2009;0.596) classification. Pathway analysis revealed that HfRI-high tumors were characterized by upregulation of cell cycle progression and DNA replication pathways, accompanied by suppression of immune signaling pathways. These biological features provide a mechanistic explanation for the reduced responsiveness to intravesical BCG therapy, underscoring the role of HfRI not only as a predictor of recurrence risk but also as a biomarker capable of identifying patients unlikely to benefit from standard BCG treatment. CONCLUSIONS: HfRI represents a robust, transcriptome-based tool for predicting frequent recurrence in NMIBC patients. The HfRI supports earlier identification of patients at risk of high-frequency recurrence, thereby supporting personalized treatment strategies.

Humans↗
PubMed2026

The 21-gene recurrence score assay as a tool for predicting recurrence risk and guiding adjuvant treatment selection in early breast cancer.

INTRODUCTION: Estrogen receptor-positive (ER+), HER2-negative breast cancer is the most common breast cancer subtype. While adjuvant endocrine therapy reduces recurrence risk, identifying which patients benefit from the addition of chemotherapy remains a key clinical challenge. The Oncotype DX&#xae; 21-gene Recurrence Score assay (Exact Sciences, via Genomic Health, Inc.) was developed to address this by quantifying distant recurrence risk and informing chemotherapy decisions in early-stage ER+/HER2- disease. AREAS COVERED: This diagnostic profile reviews the development, validation, and clinical evidence for Oncotype DX, including findings from the TAILORx and RxPONDER prospective trials and the subsequent development of hybrid tools integrating genomic and clinicopathological data. Alternative multiparameter molecular tests (MammaPrint, Prosigna, EndoPredict, Breast Cancer Index) are summarized and compared. We review international guideline recommendations, decision impact studies, cost-effectiveness evidence, and ongoing trials. EXPERT OPINION: Oncotype DX has strong prognostic evidence and has meaningfully reduced chemotherapy use, though its case as a biomarker predictive of therapeutic effect from chemotherapy rests on trial designs with important limitations. Its independent prognostic contribution beyond comprehensive clinicopathological assessment requires further clarification, and cost-effectiveness varies substantially by indication and healthcare setting.

Humans↗
PubMed1978

Defective leukocytotaxia and recurrent staphylococcal infecion: deficiency of leukocytotaxia and abnormal granulocytes associated with increase serum IgE levels in an adult with recurrent staphylococcal infection.

A man who was suffering from recurrent staphylococcal infection had antecedent symptoms of severe pruritus. Laboratory investigations showed leukocytosis with eosinophilia, hyperimmunoglobulinemia of all fractions, but particularly of IgE, and a deficiency of cell-mediated immunity on in vivo testing. Phagocytosis and bactericidal activity of polymorphonuclear leukocytes were normal, but a cellular and serum-associated defect in leukocytotaxia was present. Ultrastructural changes were observed in polymorphonuclear leukocytes. Association of impaired leukocytotaxia and elevated levels of IgE is not uncommon. Recurrent bacterial infections in the patient described are probably related to defective chemotaxis.

Aged↗
PubMed1975

Acute and recurrent infection with herpes simplex virus in the mouse: a model for studying latency and recurrent disease.

Nineteen recent isolated and three laboratory strains of herpes simplex virus types 1 and 2 were tested for their ability to produce clinical signs in mice following intradermal inoculation in the ear. All viruses produced erythema at the inoculation site; this was the most sensitive clinical sign of infection. Virus multiplication in the ear tissue was similar for both types 1 and 2 up to the fifth day after inoculation but type 2 viruses persisted for longer. Latent infection was demonstrated in cervical dorsal root ganglia. Type 1 viruses required a much higher dose than type 2 to produce neurological signs and death after intradermal inoculation but the difference was less after intracerebral inoculation. Erythema of the inoculated ear recurred sporadically during several months observation in about half the mice that survived intradermal infection with a selected type 1 isolate. The presence of virus in the ear tissue during such recurrences was confirmed by electron microscopy and isolation of infectious virus. The system of ear infection in the mouse is presented as a new model for studying neurovirulence, and latent and recurrent infection with herpes simplex virus.

Animals↗
PubMed1977

Cell-mediated immune responses in patients with recurrent Herpes Simplex infections. II. Infection-associated deficiency of lymphokine production in patients with recurrent herpes labialis or herpes progenitalis.

Herpes simplex virus antigen-induced lymphocyte proliferation and production of leukocyte migration inhibitory factor (LMIF) and lymphocyte-derived interferon were studied in normal individuals and patients with recurrent Herpes labialis and Herpes progenitalis. Virus-specific lymphoproliferative responses were regularly detected in patients with recurrent infection irrespective of the clinical stage of infection. In contrast, transient deficiencies in herpes-specific lymphoid production of both LMIF and interferon were regularly documented at the time of and immediately before herpes simplex-induced vesicular eruptions. During the convalescence, pronounced production of these mediators in response to antigenic stimulation with inactivated virus antigen preparations were regularly detected. The biology of these fluctuations in lymphokine production is evaluated and discussed.

Antigens, Viral↗
PubMed1978

Recurrent hydatidiform mole. Report of a case with five recurrences.

A report on a patient having five consecutive molar pregnancies is presented. None of the pregnancies was associated with a fetus and all five hydatidiform moles were histologically benign. The treatment of recurrent moles is discussed and the literature concerning this problem is reviewed.

Adult↗
PubMed2026

Tumor Mutational Concordance and Recurrence Timing in Hepatocellular Carcinoma.

INTRODUCTION: In hepatocellular carcinoma (HCC), intrahepatic recurrence includes true recurrence from clonal relapse and multicentric recurrence from de novo tumorigenesis. Recurrence timing is used to distinguish these types; however, its accuracy remains unclear. This study aimed to classify recurrent tumors based on somatic mutational concordance and assess the validity of recurrence timing. METHODS: Whole-exome sequencing was performed on paired primary and recurrent HCC tumors from 49 patients enrolled in a prospective institutional omics project. Tumors with &#x2265; 10 shared somatic mutations were classified as true recurrence. Clinicopathological features, recurrence timing, driver mutation patterns, and survival outcomes were compared between recurrence types. Mutational concordance was quantified using shared variant counts and the Jaccard similarity index. RESULTS: Of the 49 patients, 22 (44.9%) showed true recurrence and 27 (55.1%) had multicentric recurrence. Multicentric recurrence tumors harbored no shared variants or only a single shared variant with the primary tumor. True recurrence was associated with significantly higher concordance in histological differentiation and Edmondson-Steiner grading and greater retention of CTNNB1, TP53, ARID1A, and KEAP1 mutations. The number of shared variants (median: 115 vs. 0, and p&#xa0;<&#xa0;0.001) and the Jaccard index (median: 0.44 vs. 0.00 and p&#xa0;<&#xa0;0.001) were significantly higher in the true recurrence group. Recurrence timing was inconsistently correlated with mutational concordance, although a 3-year cutoff yielded significant separation. CONCLUSION: Recurrence timing alone insufficiently reflects clonal relationships. Genomic profiling offers a reliable framework for distinguishing between recurrence types and guiding HCC management.

clonal relapse↗
PubMed2026

TERT promoter mutations and recurrence patterns in differentiated thyroid carcinoma.

Telomerase reverse transcriptase promoter mutations (TERT) are known prognostic factors associated with poor outcomes in differentiated thyroid carcinoma (DTC). We analyzed differences in DTC recurrence patterns over time according to TERT. A retrospective review was conducted on DTC patients who achieved remission after total thyroidectomy and/or radioactive iodine treatment at Samsung Medical Center between 1994 and 2004. The sites and patterns by time of recurrence in the patients were reviewed. In total, 367 patients with a median follow-up of 14 years (interquartile range, 12-17 years) were included. Recurrence occurred in 91 patients, wherein 56 had lymph node recurrence and 35 had either local or distant recurrence. TE RT and tumor size <2 cm were independent factors for recurrence in the Cox proportional hazards analysis. In cases of TERT-wild type (WT), the recurrence rate decreased significantly over time after diagnosis, whereas in TERT-mutant type (MT), a consistently high recurrence rate was observed. In the Kaplan-Meier analysis, TERT-MT exhibited a significantly poorer disease-free survival, with continuous recurrence over time, whereas in TERT-WT, the curve showed a gradual decline. Further analysis of the overall survival among the 91 patients revealed that TERT-MT was significantly associated with a higher risk of mortality, whereas TERT-WT exhibited a slowly decreasing curve. In conclusion, TERT-MT was a significant adverse prognostic factor wherein continuous recurrence necessitates long-term follow-up. For TERT-WT, the recurrence rate decreased compared to TERT-MT, and even in cases of recurrence, the treatment outcomes are favorable.

Humans↗
PubMed2026

Nonmuscle-Invasive Recurrence and Management During Surveillance in Patients with Muscle-Invasive Bladder Cancer Who Achieve Clinical Complete Response to Neoadjuvant Chemotherapy.

PURPOSE: Many patients are medically unfit for or refuse radical cystectomy. Few postchemotherapy bladder-sparing active surveillance programs have reported on nonmuscle-invasive recurrences and treatment outcomes. In this study, we present data on nonmuscle-invasive recurrences and their management in this population. MATERIALS AND METHODS: This is a retrospective review of a prospectively maintained database. All patients received cisplatin-based neoadjuvant chemotherapy and were determined to have a clinical complete response (cCR) based on negative endoscopic resection, urine cytology, and cross-sectional imaging. Patient data were entered into a strict active surveillance protocol. Primary outcomes of interest were number of nonmuscle-invasive recurrences, grade and stage, and treatment. Secondary outcomes of interest were nonmuscle-invasive treatment response rate and muscle-invasive and metastatic recurrence rate. RESULTS: A total of 61 cCR patients were identified. In total, 28 patients experienced a median of 1 nonmuscle-invasive recurrence over a median follow-up of 28.3 months. There were a total of 46 nonmuscle-invasive recurrences, including 9 (20%) low-grade recurrences and 37 (80%) high-grade recurrences. Of the 37 high-grade recurrences, the majority (60%) were treated with Bacillus Calmette-Gu&#xe9;rin induction. Nonmuscle-invasive recurrence was not associated with later muscle-invasive recurrence or metastasis. Genomic analysis of paired tumor samples demonstrated clonal relatedness in one patient sample while another sample demonstrated a likely precancerous urothelial field effect. CONCLUSIONS: There is a high rate of nonmuscle-invasive recurrences in patients who achieve cCR to neoadjuvant chemotherapy. However, most of these patients may be safely managed with bladder-preserving treatments. These findings emphasize the importance of vigilant surveillance protocols and appropriate patient selection.

bladder cancer↗
PubMed2025

TSH Cutoffs and Recurrence Risk in Differentiated Thyroid Carcinomas: A Systematic Review and Meta-Analysis.

CONTEXT: The current American Thyroid Association (ATA) guidelines recommend tailored TSH suppression, considering the recurrence risk of differentiated thyroid cancer (DTC); however, the evidence is limited. OBJECTIVE: This meta-analysis aimed to investigate the risk of recurrence in patients with DTC, stratified by the ATA risk of recurrence, according to variable thyrotropin (TSH) cutoffs (0.1, 0.5, and 2.0 mIU/L). METHODS: We searched Ovid-Medline, EMBASE, and Cochrane databases for studies reporting the recurrence rate of DTCs based on TSH cutoffs through March 2024. The search terms used included "thyroid neoplasm" OR "cancer," "TSH" OR "thyroid stimulating hormone," "suppress" OR "supplementation," and "thyroidectomy". RESULTS: Two randomized controlled trials and 7 observational studies, including 5320 patients, were analyzed, with an overall recurrence rate of 18%. The pooled recurrence risk for DTCs at each TSH cutoff (0.1, 0.5, and 2.0 mIU/L) was not significant. In the subgroup analysis, the pooled hazard ratios (HRs) stratified by the ATA risk of recurrence (low- and high-risk DTCs) did not differ according to TSH levels. However, the risks of recurrence increased at serum TSH of 0.1 mIU/L or greater (HR 2.27; 95% CI, 1.29-3.99) and TSH of 2.0 mIU/L or greater (HR 1.36; 95% CI, 1.001-1.84) in a leave-one-out meta-analysis after removing the study that significantly influenced the analysis. Patients with distant metastases had a higher risk of recurrence (HR 3.3; 95% CI, 1.53-7.10) when maintaining a TSH greater than or equal to 0.1 mIU/L. CONCLUSION: The degree of TSH suppression did not affect the overall risk of DTC recurrence. However, TSH suppression may be beneficial in reducing the recurrence risk in high-risk patients with distant metastases.

Humans↗