Trop2-targeted immunoPET ligands.

Exosomes are recognized as promising biomarkers for early cancer diagnosis and prognosis owing to a large amount of biological information they carried. But the key is that single type of exosomal biomarker analysis is not sufficient enough for accurate cancer diagnosis and stage monitoring due to the insufficient information and high false positive signal. To address the challenge, here simultaneous in situ detection of different types of exosomal biomarkers (surface proteins: CD81, ephrin type-A receptor 2, and carbohydrate antigen 19-9; miRNAs: miR-451a, miR-21, and miR-10b) is conducted with a 3D microfluidic chip, which works in conjunction with quantum dot (QD) labeling and vesicle fusion technology. After exosomes are efficiently captured by the microfluidic chip, the quantification of multiple exosomal proteins is achieved by using three kinds of QDs with the same excitation and different emission wavelengths, and virus-mimicking fusogenic vesicles encapsulating three exquisitely engineered molecular beacons are introduced for ultrasensitive detection of multiple exosomal miRNAs without requiring RNA extraction. Through comprehensive profiling different types of exosomal biomarkers, the false positive rate is substantially avoided and the accuracy of cancer diagnosis and stage monitoring is improved to ≈100%, which are critical to cancer effective treatment and favorable prognosis.

In this retrospective study, the accuracy of preoperative staging by high-resolution CT and clinical evaluation (indirect-direct laryngoscopy) is compared to the postsurgical pathologic staging of laryngeal cancer. Forty-two patients who were admitted to St. Louis University Hospital between the years of 1978 to 1985 with diagnoses of laryngeal cancer were included. All patients received high-resolution CT scan of the larynx preoperatively and subsequently underwent total or partial laryngectomy. None of these patients received preoperative radiotherapy. The accuracy of the clinical vs. CT staging--as well as the accuracy of the staging by combination of the two modalities--was determined by comparison with the postsurgical pathologic staging. The accuracy was assessed separately for glottic, supraglottic, and transglottic carcinoma. The accuracy of CT staging for glottic carcinoma was 75%. However, clinical evaluation in this group of lesions was very reliable, offering 92.9% accuracy. The accuracy of CT staging increased in the supraglottic and transglottic lesions, to become superior to the clinical staging. With combined information gained by both examinations, the preoperative staging accuracy was 91.4% for supraglottic carcinoma and 87.5% for transglottic carcinoma. It is, therefore, recommended that high-resolution CT should be included in the preoperative staging of laryngeal cancer.

Response

Cross sectional imaging is important for initial evaluation of pancreatic cancer, whereas endoscopic ultrasound (EUS) will often help better visualize, differentiate and make final tissue diagnosis. It plays an important role in the multi-disciplinary evaluation and staging of pancreatic cancer as accurate staging has significant impact on treatment decisions. This review will cover the yield and utility of EUS and EUS FNA for diagnosis of pancreas cancer. In addition, this article reviews the utility and diagnostic yield of the non-invasive imaging modalities, including surface ultrasound, CT scan, PET CT scan and MRI. Tumor size, histology and disease processes that mimic pancreatic cancers will also be reviewed. The accurate diagnosis and staging of pancreatic neoplasms is essential for optimal patient management. Abdominal imaging with multidetector CT or MRI is the most important initial step in the evaluation of pancreatic cancer because they are widely available and can detect most masses and/or demonstrate dilated bile or pancreatic ducts indicative of obstruction. Endoscopic ultrasound will remain important for detecting small tumors, ruling out diseases that mimic adenocarcinoma and for obtaining tissue diagnosis with fine needle aspiration.

Simple SummaryPancreatic cancer ranks as the seventh leading cause of cancer-related death worldwide. The overall prognosis of pancreatic cancer is poor even in patients with resectable disease. Early detection and accurate diagnosis and staging of pancreatic cancer are essential for developing a treatment strategy, as surgical resection can provide the only potential cure for this disease. Endoscopic ultrasonography is essential in the diagnosis and loco-regional staging of the disease.Pancreatic cancer is the fourth leading cause of cancer-related death and the second gastrointestinal cancer-related death in the United States. Early detection and accurate diagnosis and staging of pancreatic cancer are paramount in guiding treatment plans, as surgical resection can provide the only potential cure for this disease. The overall prognosis of pancreatic cancer is poor even in patients with resectable disease. The 5-year survival after surgical resection is ~10% in node-positive disease compared to ~30% in node-negative disease. The advancement of imaging studies and the multidisciplinary approach involving radiologists, gastroenterologists, advanced endoscopists, medical, radiation, and surgical oncologists have a major impact on the management of pancreatic cancer. Endoscopic ultrasonography is essential in the diagnosis by obtaining tissue (FNA or FNB) and in the loco-regional staging of the disease. The advancement in EUS techniques has made this modality a critical adjunct in the management process of pancreatic cancer. In this review article, we provide an overall description of the role of endoscopic ultrasonography in the diagnosis and staging of pancreatic cancer.

Chapter 4 - Learning from multiple modalities of imaging data for cancer diagnosis

Accurate staging is crucial for the treatment and prognosis of patients with endometrial cancer. Based on the 2009 staging system, the International Federation of Gynecology and Obstetrics (FIGO) published updated staging system in 2023, incorporating factors such as tumor tissue type, histological grading, lymphovascular space invasion, low-volume lymph node metastasis and molecular profiling. However, the real world clinical application value of the new staging is still unclear. Therefore, this review focused on the updation details and discussed the clinical significance of FIGO 2023 staging system, comparing the difference and the clinical practice impact between the "new" and "old" staging systems. Through this review, it is expected that the accurate diagnosis and treatment of endometrial cancer could be improved, and practical guidance for the clinical diagnosis and treatment of endometrial cancer would be provided.

The diagnosis and staging of bladder cancer: From RBCs to TURs

The logic profiling of exosomal microRNAs (miRNAs) offers broad potential applications in the accurate diagnosis and staging of cancer. However, the logical detection of low-abundance exosomal miRNAs in complex clinical samples remains challenging. This study introduces a logic analysis system termed "Measurer" (a multi-enzyme-assisted ultrasensitive circuit) that offers ultrasensitive and versatile method for detecting multiple exosomal miRNAs. The Logic-Measurer comprises three modules: a stem-loop hairpin-enhanced CRISPR/Cas13a, a polymerase-driven primer exchange reaction, and an exonuclease III-mediated fluorescence output. The efficient Logic-Measurer was switched by the faster rate of trans-cleavage activity of Cas13a due to its improved affinity for hairpin RNA structures. The mechanistic model of hairpin-enhanced CRISPR/Cas13a was confirmed by molecular dynamics simulations. The Logic-Measurer accurately detected exosomal miRNA-21 or miRNA-375 down to 2.1 and 4.4 fM, with superior specificity, and enabled in situ detection of miRNA-21 and miRNA-375 in as low as 1.4 × 102 particles/mL exosomes via membrane fusion. In addition, this method demonstrated 87.3 and 82.1% accuracy in the diagnosis and early detection of breast cancer, respectively, among a cohort of 315 individuals. Subsequent subgroup analysis further confirmed the method's ability to accurately differentiate estrogen receptor-positive patients from healthy individuals. Therefore, the Logic-Measurer offers valuable insights into the development of a CRISPR/Cas-based enhanced diagnostic platform and the next generation of diagnostic technology based on enzyme circuits.

Simple SummaryProstate cancer is one of the most dominant cancers in the Western world. In recent years, the use of positron emission tomography (PET) targeting prostate-specific membrane antigen (PSMA) to image prostate cancer allows accurate diagnosis and staging. Compared to the recently registered PET tracers [68Ga]Ga-PSMA-11 and [18F]DCFPyL, [18F]PSMA-1007 is predominantly excreted by the hepatobiliary tract, resulting in much lower urinary uptake. This allows for an improved evaluation of the pelvic area. However, on some occasions, clinicians do observe high excretion of [18F]PSMA-1007 by the renal system. Yet, this sudden differential metabolism of [18F]PSMA-1007 remains poorly understood. In this retrospective study, we aimed to elucidate the incidental high urinary uptake of [18F]PSMA-1007 by assessing the individual patient characteristics, scan (data) and peptide batches.Positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) allows for accurate diagnosis and staging of prostate cancer (PCa). Compared to other PSMA PET tracers available, [18F]PSMA-1007 is predominantly excreted via the hepatobiliary tract resulting in low renal excretion which improves evaluation of the pelvic area. However, some patients do show high urinary uptake of [18F]PSMA-1007. The present study aimed to investigate this sudden high urinary uptake of [18F]PSMA-1007 by evaluating [18F]PSMA-1007 PET scans from PCa patients. In this single-center retrospective study, patients that underwent [18F]PSMA-1007 PET imaging between July 2018 and January 2021 were included. Data regarding the individual patient characteristics, scan acquisition and batch production were analyzed. To determine the urinary excretion of [18F]PSMA-1007, a region of interest was drawn in the bladder, and standardized uptake values (SUVs) were calculated and compared to SUVs in the prostate. An SUVmax of >10 was considered high urinary excretion, an SUVmax 7.5–10 intermediate and an SUVmax < 7.5 low urinary excretion. A total of 344 patients underwent [18F]PSMA-1007 PET/CT imaging, with 37 patients receiving three or more [18F]PSMA-1007 PET/CT scans. The mean SUVmean and SUVmax of the bladder were 3.9 (SD 2.9) and 5.9 (SD 4.2), respectively. Fourteen percent of patients showed high urinary uptake of [18F]PSMA-1007. Twelve of the thirty-seven patients (32.4%) that had multiple scans showed a varying urinary uptake of [18F]PSMA-1007 per PSMA PET/CT scan. In terms of patient characteristics, risk factors, medication and blood laboratory results, no significant influencing variables were found. Nor was there a difference observed in the batch size and the mean radiochemical purity of PSMA-1007 for high- and low-excreting patients. However, the bladder volume affected the mean SUVmax in the bladder significantly, with higher SUVs in lower bladder volumes. In this study, we observed that a higher SUV in the urinary tract seemed to occur in patients with low bladder volume. A prospective study is needed to corroborate this hypothesis.

An accurate staging diagnosis of rectal cancer holds crucial importance in determining the appropriate treatment plan for patients. To evaluate the application of transrectal biplane ultrasonography combined with Sound Touch Elastography (STE) technology in preoperative uT stage of rectal cancer. A retrospective analysis was conducted on the ultrasonographic data of 32 patients. The STE values within the tumor and the adjacent peritumoral fat tissue were recorded, and the ratio of STE values between adjacent and distant peritumoral fat tissues was defined as the Stiffness Ratio (SR). The STE values were not statistically significantly different between the high and low pT stage groups within tumors (P > 0.05). However, there were statistically significant differences in the STE values of the adjacent peritumoral fat tissue and the SR between the two groups (P < 0.05). Binary logistic regression analysis showed that the SR was a relevant factor in distinguishing high and low pT stages of rectal cancer. The optimal cut-off value of the SR was 1.915, with a sensitivity of 95.7% and a specificity of 88.9% in predicting high pT stages of rectal cancer. The consistency observed between traditional TRUS and pathological staging in differentiating between high and low pT stages of rectal cancer was moderate. However, the incorporation of SR had enhanced this consistency to a favorable level. The combination of TRUS and STE technology enhanced the accuracy of pT stage in rectal cancer, with SR serving as a critical indicator for predicting high pT stages and constituting a valuable supplement to traditional TRUS.

We evaluated the correlation of radiological findings obtained by MRI study with pathological diagnosis in invasive bladder cancer treated with neoadjuvant chemotherapy, with or without radiation. Twenty-seven patients, who underwent total or partial cystectomy for invasive bladder tumors, were enrolled into the present study. Eight cases had received neoadjuvant chemotherapy following the staging biopsy (group A), ten cases had received chemo-radiation therapy following the staging biopsy (group B), and nine cases had received preoperative staging biopsy alone (group C). As a final treatment, 12 of the 27 patients underwent total cystectomy and the other 15 patients underwent partial cystectomy. MRI was conducted prior to total or partial cystectomy in each case. The pathological stage was assessed by histological examination of the entire layer of the bladder wall. Tumor stage assessed by MRI was consistent with pathological findings in 16 of the 27 cases (59.3%), while MRI produced over-staging in 7 cases and under-staging in 4 cases. The accuracy of staging was 75.0, 30.0, and 77.8% in groups A, B, and C, respectively. The accuracy of MRI staging in group B was lower than that in group C (P < 0.05). There was no difference in the accuracy of MRI staging between groups A and C. MRI is useful for the staging of bladder cancer. However, care needs to be taken when staging invasive bladder tumors treated with neoadjuvant chemo-radiation therapy, because inflammatory infiltrations and/or fibrous changes caused by the chemotherapy or chemo-radiation therapy make precise staging with MRI difficult.

Cancer stage documentation and accuracy: Single-center retrospective study on oropharyngeal cancers.

Rationale and Objectives: Accurately establishing the diagnosis and staging of cervical and thyroid cancers is essential in medical practice in determining tumor extension and dissemination and involves the most accurate and effective therapeutic approach. For accurate diagnosis and staging of cervical and thyroid cancers, we aim to create a diagnostic method, optimized by the algorithms of artificial intelligence and validated by achieving accurate and favorable results by conducting a clinical trial, during which we will use the diagnostic method optimized by artificial intelligence (AI) algorithms, to avoid errors, to increase the understanding on interpretation computer tomography (CT) scan, magnetic resonance imaging (MRI) of the doctor and improve therapeutic planning. Materials and Methods: The optimization of the computer assisted diagnosis (CAD) method will consist in the development and formation of artificial intelligence models, using algorithms and tools used in segmental volumetric constructions to generate 3D images from MRI/CT. We propose a comparative study of current developments in “DICOM” image processing by volume rendering technique, the use of the transfer function for opacity and color, shades of gray from “DICOM” images projected in a three-dimensional space. We also use artificial intelligence (AI), through the technique of Generative Adversarial Networks (GAN), which has proven to be effective in representing complex data distributions, as we do in this study. Validation of the diagnostic method, optimized by algorithm of artificial intelligence will consist of achieving accurate results on diagnosis and staging of cervical and thyroid cancers by conducting a randomized, controlled clinical trial, for a period of 17 months. Results: We will validate the CAD method through a clinical study and, secondly, we use various network topologies specified above, which have produced promising results in the tasks of image model recognition and by using this mixture. By using this method in medical practice, we aim to avoid errors, provide precision in diagnosing, staging and establishing the therapeutic plan in cancers of the cervix and thyroid using AI. Conclusion: The use of the CAD method can increase the quality of life by avoiding intra and postoperative complications in surgery, intraoperative orientation and the precise determination of radiation doses and irradiation zone in radiotherapy.

EUS staging of primary lung carcinoma: are we ready for it?