Diagnosis Of Tumors Research Articles

An Integrated Multimodal-Based CAD System for Breast Cancer Diagnosis

Breast cancer has been one of the main causes of death among women recently, and it has been the focus of attention of many specialists and researchers in the health field. Because of its seriousness and spread speed, breast cancer-resisting methods, early diagnosis, diagnosis, and treatment have been the points of research discussion. Many computers-aided diagnosis (CAD) systems have been proposed to reduce the load on physicians and increase the accuracy of breast tumor diagnosis. To the best of our knowledge, combining patient information, including medical history, breast density, age, and other factors, with mammogram features from both breasts in craniocaudal (CC) and mediolateral oblique (MLO) views has not been previously investigated for breast tumor classification. In this paper, we investigated the effectiveness of using those inputs by comparing two combination approaches. The soft voting approach, produced from statistical information-based models (decision tree, random forest, K-nearest neighbor, Gaussian naive Bayes, gradient boosting, and MLP) and an image-based model (CNN), achieved 90% accuracy. Additionally, concatenating statistical and image-based features in a deep learning model achieved 93% accuracy. We found that it produced promising results that would enhance the CAD systems. As a result, this study finds that using both sides of mammograms outperformed the result of using only the infected side. In addition, integrating the mammogram features with statistical information enhanced the accuracy of the tumor classification. Our findings, based on a novel dataset, incorporate both patient information and four-view mammogram images, covering multiple classes: normal, benign, and malignant.

The role of disease modifying therapies in late-onset multiple sclerosis: A Portuguese multicentric characterization study

IntroductionKnowledge about the effect of disease modifying treatment (DMT) in late-onset multiple sclerosis (LOMS, onset ≥50 years-old) is scarce. This study aims to evaluate the association between DMT use and multiple sclerosis (MS) evolution in a LOMS cohort. MethodsThis multicentre, retrospective and observational study included LOMS patients with ≥2 years of follow-up. Data on demographics, clinical/paraclinical (baseline and follow-up), DMT and adverse events were collected. Primary outcomes were irreversible EDSS 4.0 and 6.0 achievement and first year ARR. Univariate and multivariate regression models were conducted, with treated and/or relapsing phenotypes (RMS) subgroups analyses. ResultsWe included 232 patients (53.4 % with RRMS phenotype; 84.9 % submitted to DMT; median follow-up time of 141.5 (IQR 92.7–193.1) months). Treatment versus non-treatment did not affect EDSS milestones in multivariate analysis (adjusted to phenotype, baseline EDSS, age, and ARR), but initially receiving monoclonal antibodies (MAbs) was associated with lower odds of EDSS 4.0 (OR 0.13). In treated patients, starting with high efficacy DMT (HE-DMT) was related to a lower chance of EDSS 4.0 (OR 0.05) and 6.0 (OR 0.26) compared with being exclusively treated with moderate efficacy DMT (ME-DMT), with similar results when analysing the subgroup of RMS treated patients. In multivariate models, initial treatment with MAbs (vs. non-treatment) and with HE-DMT (vs. ME-DMT) were related to a lower first year ARR; when considering only RMS patients, every DMT class analysed reduced first year ARR vs. non-treatment. During DMT, we documented a rate of 0.6 % serious infections, 0.07 % opportunistic infections and 0.7 % neoplasm diagnosis per patient year. ConclusionDMT type and therapeutic strategy influenced LOMS disability accumulation and relapses in our cohort. Our findings support the importance of investment in LOMS treatment optimization.

Mitochondrial Proteome Defined Molecular Pathological Characteristics of Oncocytic Thyroid Tumors.

Oncocytic thyroid tumors are characterized by an elevated mitochondrial density within the cells, distinguishing them from other thyroid tumors, exhibit distinct clinical behaviors, including increased invasiveness and iodine therapy resistance. However, the proteomic alterations in oncocytic thyroid tumors remain inadequately characterized. In this study, we analyzed 156 Asian patients with oncocytic thyroid adenomas (OA) and carcinomas (OCA) to explore their clinical, genetic, and proteomic features. Genetic testing of 73 samples revealed frequent mutations in TERT, NRAS, EIF1AX, EZH1, and HRAS, with TERT promoter mutations being exclusive to OCAs. Proteomic analysis identified 66 mitochondrial-specific proteins significantly highly expressed in oncocytic tumors than in non-oncocytic tumors. This led to the development of a thyroid oncocytic score (TOS) to quantify oncocytic characteristics. Among these proteins, isocitrate dehydrogenase 2 (IDH2) was substantially overexpressed in oncocytic tumors and further confirmed by immunohistochemistry in oncocytic tumor slides (n = 41) and non-oncocytic tumor slides (n = 40). Moreover, IDH2 is significantly overexpressed in OCA compared to OA highlighting its potential as a biomarker for differential diagnosis of oncocytic tumors and malignancy. These findings improve the understanding of oncocytic thyroid tumors molecular pathology and suggest IDH2 as a valuable marker for clinical management.

089. TACE for Residive Malignant Peripheral Nerve Sheath Tumor and Leiomyosarcoma: Case Series

Background: Malignant peripheral nerve sheath tumors (MPNST) are malignant, locally aggressive soft tissue sarcomas (STS) of the peripheral nerve or nerve sheath cells. Leiomyosarcomas are malignant tumors originating from the smooth muscle. Transarterial chemoembolization (TACE) is an interventional treatment to deliver chemoembolic materials. Case: First case is a 50-year-old male visited Oncology Surgery Polyclinic due to the presence of a tumor on his left forearm that was progressively increasing in size during the past two months. The MRI was done, the diagnosis of a residive malignant peripheral nerve sheath tumor was made. Second case is a 40-year-old female visited the Oncology Surgery Polyclinic due to the presence of a tumor on her right breast that was progressively increasing in size and the diagnosis of a Leiomyosarcoma at the right breast was made. Transarterial chemoembolization (TACE) was performed to both of the cases. Conclusion: MPNST and Leiomyosarcoma are malignant tumor that can be treated with doxorubicin chemotherapy through the TACE procedure.

Intracranial pleomorphic liposarcoma misclassified as a pleomorphic xanthoastrocytoma by a DNA methylation classifier: illustrative case.

Recently, it has been shown that DNA methylation arrays and German Cancer Research Center (Deutsches Krebsforschungszentrum) methylation classifiers are useful aids in brain tumor diagnosis for cases in which histopathological diagnosis is difficult. However, not enough is known about diagnostic aids for intracranial liposarcoma (LPS). An 18-year-old woman with a history of natural killer/T-cell lymphoma, which had been treated with a bone marrow transplant and total body irradiation at age 11 years, presented with diplopia. Magnetic resonance imaging revealed a brain tumor in the posterior left temporal lobe, which was removed by craniotomy. The tumor was initially diagnosed as pleomorphic xanthoastrocytoma through histopathological and DNA methylation examination. She also had a soft tissue tumor in her left thigh, which was removed. It contained spindle cells with oval nuclei and highly pleomorphic cells and was diagnosed as radiation-induced LPS. Histopathological re-examination of the brain tumor led to a final diagnosis of pleomorphic LPS. In this report, the authors describe the case of a patient with an intracranial pleomorphic LPS that was initially classified as a pleomorphic xanthoastrocytoma by a DNA methylation classifier. Although DNA methylation classifiers are useful as diagnostic aids in cases in which definitive pathology is difficult to determine, there is a risk of misdiagnosis in some types of tumors. https://thejns.org/doi/10.3171/CASE24465.

Pediatric Cutaneous T-Cell Neoplasms: Clinical and Pathological Features, Updated Classifications, and CriticalDifferential Diagnoses.

Cutaneous T-cell lymphoid neoplasms in childhood are exceedingly rare, presenting with a wide spectrum of clinical presentation and outcomes. Due to numerous clinical and pathological mimics, an integrated evaluation of clinical, histopathological, immunohistochemical, and molecular findings is critical for a diagnosis. Here, we review the clinical and pathological features, updated classifications, and critical differential diagnoses of cutaneous T-cell lymphoid neoplasms in children.

The method for evaluating the symmetry of the globule pattern in artificial intelligence systems for the diagnosis of skin neoplasms

Methods for early non-invasive diagnosis of melanoma using computer vision systems are considered. Existing computer vision systems using neural networks for classifying dermoscopic images do not allow tracking which diagnostic features are used to assign images to a particular class, reducing physicians' trust in the results. As an alternative, an image analysis algorithm is proposed with the ability to present justifications for decisions made at each processing stage. The implementation of this algorithm is based on the medical algorithm of modified globular pattern analysis. A significant sign of malignancy in a neoplasm is its asymmetry. This criterion is widely used by doctors in visual assessment of skin neoplasms. However, currently, the issues of evaluating the symmetry of globular patterns in artificial intelligence systems are not fully studied and described. A method for evaluating the symmetry of globular patterns in artificial intelligence systems for diagnosing skin neoplasms has been developed. A dataset of dermoscopic images was formed, containing 50 images each of neoplasms with symmetrically and asymmetrically arranged globular patterns. Methods for isolating the neoplasm area and globules are described. A classification system based on a set of 12 quantitative symmetry characteristics has been developed. The Random Forest algorithm was used to classify images based on symmetry features. In the conducted experiment, a classification accuracy of 85% was achieved. The presented results contribute to the development of computer vision methods in dermatology and demonstrate the possibility of using the proposed method in clinical decision support systems for modified analysis of dermoscopic patterns for diagnosing skin neoplasms.

Ultrasound-guided core-needle biopsy for extra-ocular orbital soft tissue tumours: a minimally invasive alternative to surgical biopsy

PurposeTo assess the feasibility, accuracy, and safety of ultrasound (US)-guided coaxial core-needle biopsy (CNB) for histomolecular diagnosis of extra-ocular orbital soft tissue tumours as a minimally invasive alternative to surgical biopsy. MethodsThis retrospective study was conducted at a single Comprehensive Cancer Center and included all consecutive patients referred to our center between 2015 and 2023 for the diagnosis and treatment of orbital soft tissue tumours. All patients underwent US-guided transconjunctival coaxial CNB using a semiautomatic 18-gauge biopsy gun. Pathological analysis included morphological analysis, immunostainings, and molecular biology techniques when required. ResultsA total of 26 patients were included consisting of 21 adults (median age: 64 years, range: 24-93 years), 1 adolescent (17 years), and 4 children (aged 4 weeks, 5 weeks, 26 months, and 6 years). Tumour largest diameters ranged from 11 to 57 mm (median 23 mm). The overall feasibility of CNB was 88% (23/26), and it was 100% (5/5) in children. The histological accuracy was 91% (21/23), and its safety was 96% (25/26). Molecular biology analyses were requested in 9 out of 23 cases and were successful in all instances. The final diagnoses included hematological malignancies (n = 8), carcinomas (n = 5), metastases (n = 4), sarcomas (n = 4), and benign mesenchymal tumours (n = 5). ConclusionsThis study supports the use of US-guided coaxial CNB for the pathological and molecular diagnosis of orbital soft tissue tumours in both children and adults. This technique shows promise as a minimally invasive alternative to open surgical biopsy.

Clinical Applications of Circulating Tumor DNA Profiling in GI Cancers

Over the next few years, the analysis of circulating tumor DNA (ctDNA) through liquid biopsy is expected to enter clinical practice and revolutionize the approach to biomarker testing and treatment selection in GI cancers. In fact, growing evidence support the use of ctDNA testing as a noninvasive, effective, and highly specific tool for molecular profiling in GI cancers. Analysis of blood ctDNA has been investigated in multiple settings including early tumor detection, minimal residual disease evaluation, tumor diagnosis and evaluation of prognostic/predictive biomarkers for targeted treatment selection, longitudinal monitoring of treatment response, and identification of resistance mechanisms. Here, we review the clinical applications, advantages, and limitations of ctDNA profiling for precision oncology in GI cancers.

High-sensitivity and spatial resolution benchtop cone beam XFCT imaging system with pixelated photon counting detectors using enhanced multipixel events correction method

Objective.High atomic number element nanoparticles have shown potential in tumor diagnosis and therapy. X-ray fluorescence computed tomography (XFCT) technology enables quantitative imaging of high atomic number elements by specifically detecting characteristic x-ray signals. The potential for further biomedical applications of XFCT depends on balancing sensitivity, spatial resolution, and imaging speed in existing XFCT imaging systems.Approach.In this study, we utilized a high-energy resolution pixelated photon-counting detector for XFCT imaging. We tackled degradation caused by multi-pixel events in the photon-counting detector through energy and interaction position corrections. Sensitivity and spatial resolution imaging experiments were conducted using PMMA phantoms to validate the effectiveness of the multi-pixel events correction algorithm.Main results.After correction, the system's sensitivity and spatial resolution have both improved. Furthermore, XFCT/CBCT dual-modality imaging of gadolinium nanoparticles within mice subcutaneous tumor was successfully achieved.Significance.These results demonstrate the preclinical research application potential of the XFCT/CBCT dual-modality imaging system in high atomic number nanoparticle-based tumor diagnosis and therapy.

Dual-locked NIR fluorescent probe for detection of GSH and lipid droplets and its bioimaging application in cancer model

Fluorescence probes with outstanding merits have wide applications in tumor diagnosis. However, most of these probes can only detect single tumor biomarker, potentially generating “false positive” signals within intricate biological systems. In contrast, the dual-locked fluorescent probes triggered by two response factors can effectively address the aforementioned limitations. In this work, we fabricated a novel coumarin-based NIR fluorescent probe (CP-GSH), demonstrating dual-responsiveness to high glutathione (GSH) concentrations and high viscosity. Specifically, the probe showed strong fluorescence enhancement at 675 nm ∼ 725 nm in the simultaneous presence of GSH and high viscosity, whereas the presence of either GSH or high viscosity alone could not induce a noticeable change in fluorescence intensity of CP-GSH. More importantly, the bioimaging experiments further validated CP-GSH triggered by endogenous GSH possessed excellent targeting capability towards lipid droplets (LDs), which could be utilized to effective discriminate between cancer cells and normal cells. This work proposes a promising strategy for the design of dual-locked probe for tumor imaging.

Childhood Heart Tumors: Detection, Diagnosis, and Treatments

: Childhood cardiac tumors are rare but challenging conditions that can have a significant impact on a child’s health and even be fatal if not detected and diagnosed timely. While various types of tumors can occur in the heart, the most common among children are benign tumors, such as rhabdomyomas. Diagnosis of pediatric cardiac tumors is often challenging and requires a combination of clinical examination, imaging studies and biopsy. In some cases, the tumors may be asymptomatic and discovered incidentally, while in others, they can cause symptoms, such as shortness of breath, chest pain, arrhythmias and congestive heart failure. Treatment options for pediatric cardiac tumors vary depending on the type, size and location of the tumor and may include surgical resection, watchful waiting or a combination of both. The prognosis for children with cardiac tumors is generally good, with a high rate of complete cure in many cases. However, long-term follow-up and monitoring are important to detect and manage any potential complications or recurrence of the tumors.

Pancancer analysis of the interactions between CTNNB1 and infiltrating immune cell populations.

Recently, evidence has indicated that CTNNB1 is important in a variety of malignancies. However, how CTNNB1 interacts with immune cell infiltration remains to be further investigated. In this study, we focused on the correlations between CTNNB1 and tumorigenesis, tumor progression, mutation, phosphorylation, and prognosis via gene expression profiling interaction analysis; TIMER 2.0, cBioPortal, GTEx, CPTAC, and GEPIA2 database analyses; and R software. CTNNB1 mutations are most found in uterine endometrioid carcinoma and hepatocellular carcinoma. However, no CTNNB1 mutations were found to be associated with a poor prognosis. In addition, CTNNB1 DNA methylation levels were higher in normal tissues than in tumor tissues in cancer except for breast invasive carcinoma, which had higher methylation levels in tumor tissues. The phosphorylation level of the S675 and S191 sites of CTNNB1 was greater in the primary tumor tissues in the clear cell renal cell carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, pancreatic adenocarcinoma, and breast cancer datasets but not in the glioblastoma multiform dataset. As for, with respect to immune infiltration, CD8 + T-cell infiltration was negatively correlated with the expression of CTNNB1 in thymoma and uterine corpus endometrial carcinoma. The CTNNB1 level was found to be positively associated with the infiltration index of the corresponding fibroblasts in the TCGA tumors of colon adenocarcinoma, human papillomavirus-negative head and neck squamous cell carcinoma, mesothelioma, testicular germ cell tumor, and thymoma. We also identified the top CTNNB1-correlated genes in the TCGA projects and analyzed the expression correlation between CTNNB1 and selected target genes, including PPP4R2, RHOA, and SPRED1. Additionally, pathway enrichment suggested that NUMB is involved in the Wnt pathway. This study highlights the predictive role of CTNNB1 across cancers, suggesting that CTNNB1 might serve as a potential biomarker for the diagnosis and prognosis evaluation of various malignant tumors.

Cancer of Unknown Primary Site: A New Era of Practice-Changing Approaches to Diagnosis, Staging, and Precision Therapy

The enigmatic syndrome of metastatic cancer of unknown primary (CUP) site has frustrated physicians and patients for decades. There has been debate whether CUP is a single biologically distinct cancer or a constellation of many different cancers with clinically undetectable anatomic primary sites. For the past 40 years, the diagnosis of a specific cancer type for most patients was indeterminate, and fit patients were usually treated as a single cancer with the same empiric chemotherapy (EC) regimens with poor overall results. The aggregate data from autopsies, clinical observations, specialized standard pathology, molecular testing, and several clinical trials support CUP as a multitude of clinically occult invasive primary tumors requiring different site-specific therapies (SSTs). In the past several years, improved genomic testing has been used, and the addition of molecular-guided therapies (MGTs) and immunotherapy (IO) has been shown to be superior for many different advanced cancers. Two older randomized prospective trials conducted before the advent of IO and most MGT failed to show a better outcome for patients with molecularly diagnosed cancers who received SST (tailored chemotherapy regimens) versus EC, although patients with more responsive tumor types appeared to benefit. Two recently reported randomized trials documented the clinical relevance of molecular diagnosis and comprehensive genomic profiling. The administration of improved precision SST guided by molecular diagnosis and characterization revealed significantly improved outcomes compared with EC. The management of patients with CUP is undergoing rapid change including the diagnosis of the presumed primary tumors, TNM staging for selected patients, molecular profiling, and an expanded improved role of precision therapies highlighting the rapid emergent new era of practice changing standards of care.

Accuracy of clinical diagnosis, imaging methods, and biopsy in tumours and pseudo-tumours of the hand

Accuracy of clinical diagnosis, imaging methods, and biopsy in tumours and pseudo-tumours of the hand

O12 MULTI-centre feasibility study to assess the use of 99m Tc-sestaMIBI SPECT/CT in the diagnosis of kidney tumours (MULTI-MIBI study)

O12 MULTI-centre feasibility study to assess the use of 99m Tc-sestaMIBI SPECT/CT in the diagnosis of kidney tumours (MULTI-MIBI study)

Analysis of Molecular Testing for Suspected Myeloproliferative Neoplasm at a Hybrid Community-Academic Health System

Testing for somatic mutations in JAK2, MPL, and CALR genes is a crucial element in the diagnosis of myeloproliferative neoplasms (MPN). This may have inadvertently led to increased requests for testing to “rule out MPN,” including clinical situations with low pre-test probability. This paper examines JAK2, MPL, and CALR testing by next generation sequencing (NGS) with the goal of formulating practical guidelines to make test utilization more efficient and effective. NGS results from 1482 patients tested between 2015 and March 2022 were retrieved, along with corresponding bone marrow biopsies and CBC results performed within 90 days prior to NGS and 245 (16.5%) cases were positive for pathogenic variants in JAK2, MPL, or CALR genes.The findings showed an increase in the proportion of positive cases with patient age, and a statistically significant difference in RBC counts and platelet counts among patients with positive versus negative results. Utilizing these factors, simple algorithms were constructed to predict positive results with a maximum sensitivity of 91%, while potentially eliminating 28% of negative tests. However, these models still failed to identify ∼9% of patients with MPNs. Among these “missed” patients, many had either primary myelofibrosis or MDS/MPN. Considering a simple triage model to help guide MPN testing could represent a more cost effective approach, particularly if “missed” patients could be further reduced.

A Comparative Study on BRAFV600E Mutation, Sonographic Findings, and Pathologic Characteristics in Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP) and Invasive Follicular Variant of Papillary Thyroid Carcinoma (IFVPTC)

Objective: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) comprise a new subgroup of thyroid tumors of follicular origin with borderline histologic features that lack evidence of either capsular or vascular invasion. In contrast to the invasive follicular variant of papillary thyroid carcinoma (IFVPTC), adverse events such as cancer-related death, distant or regional metastases, and structural or biochemical recurrence do not occur in patients with NIFTP. Many studies have been done to elucidate these two specific types of papillary thyroid cancer (PTC) and reduce aggressive therapeutic actions. This study compares molecular, cytological, and radiologic features of NIFTP and IFVPTC. Materials and Methods: Two groups of patients with NIFTP and IFVPTC (n = 18 in each group) who were referred to the endocrine clinic, at Imam Reza Hospital, were enrolled in this crosssectional study. Molecular analysis for BRAFV600E mutation of thyroid tissue was evaluated for all cases. Patient data included: age, sex, type of surgery, thyroid sonographic findings, and prior cytological diagnosis with the Bethesda system for reporting thyroid cytopathology. Results: Only two cases in the IFVPTC group were positive for BRAFV600E mutation. The majority of NIFTP cases were diagnosed as benign lesions (8/18). In contrast, the majority of IFVPTC cases were diagnosed as suspicious for malignancy on cytology (7/18). The mean nodule size in ultrasound in the NIFTP group (41.81 ± 20.43 mm) was larger than the IFVPTC group (36.72 ± 20.73 mm) (p =0.47). Most cases in the IFVPTC group had significantly multiple nodules (72.2%), while most cases in the NIFTP group (81.3%) had solitary nodules. Nodule composition in both groups was solid and complex; however, no cystic nodules were detected in ultrasound examinations. Furthermore, no calcification or lymphadenopathy was seen in the majority of cases in ultrasound. In the IFVPTC group, 47.1% and 35.3% of nodules were hyperechoic and hypoechoic, respectively, while 23.1%, 38.5%, and 23.1% of nodules in the NIFTP group were heterogenic, hyperechoic, and hypoechoic, respectively. Conclusion: According to our findings, only 11.1% of IFVPTC cases were BRAFV600E-positive, while none of the patients in the NIFTP group showed this mutation. However, IFVPTC was predominantly associated with a preceding diagnosis of PTC on FNA, and NIFTP was associated with the preceding diagnosis of benign lesions and follicular neoplasm. Sonographic findings failed to distinguish NIFTP from IFVPTC.

Ultrasonographic liver nodules are more often benign lesions in dogs with hemoperitoneum secondary to splenic tumor rupture.

To evaluate the reliability of preoperative abdominal ultrasonography as a staging tool for dogs with hemoperitoneum due to presumed splenic tumor rupture, focusing on the detection of metastatic lesions in the liver. 99 dogs from 20 emergency and specialty hospitals across the US. Dogs with nontraumatic hemoperitoneum secondary to splenic tumor rupture were included. A post hoc analysis was conducted on data from a nationwide prospective trial investigating novel treatments for canine hemangiosarcoma. The accuracy of preoperative staging was assessed by comparing ultrasonographic findings with intraoperative observations and histologic findings. On preoperative ultrasonography, there was a 20% incidence of liver lesions identified, with no association to liver lesions seen during operation. Notably, 22% of liver lesions observed during operation were missed on preoperative ultrasonography. The presence of liver lesions on preoperative ultrasonography was associated with a higher likelihood of a benign splenic tumor diagnosis. There was no association between the identification of liver lesions on preoperative ultrasonography and the presence of metastatic disease on liver biopsy, with a sensitivity and specificity of 19% and 82%, respectively. Additionally, ultrasound had low sensitivity in detecting intra-abdominal lesions beyond the liver and spleen, with 82% of these lesions missed preoperatively. This study challenges conventional perceptions around the approach to staging in dogs with hemoperitoneum. These findings advocate for a reevaluation of the staging approach, with more comprehensive modalities like whole-body CT or MRI potentially being more warranted.

Recent Development of Organic Afterglow Probes for Diagnosis and Treatment of Cancer

Afterglow imaging plays a crucial role in the cancer treatment field. In contrast to inorganic afterglow imaging agents, organic afterglow imaging agents possess easily modifiable structures and exhibit excellent biocompatibility, thereby presenting significant prospects for application in tumor diagnosis and management. In this review, we summarize the design principles and applications of afterglow probes in tumor imaging and therapy. Finally, we discuss the future challenges and prospects of organic afterglow probes in cancer diagnosis and therapy.