-
Molecular Imaging and Radionuclide... Jun 2024Neuroendocrine tumors (NETs) of the breast represent 1% of breast carcinomas. Histopathological misinterpretation of breast NET is common. We present the case of a...
Neuroendocrine tumors (NETs) of the breast represent 1% of breast carcinomas. Histopathological misinterpretation of breast NET is common. We present the case of a female patient who had a breast mass diagnosed as invasive ductal carcinoma initially by histopathological examination. Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) revealed 2 ametabolic hypodense liver lesions. Subsequently, the patient underwent fibroblast activation protein inhibitor (FAPI)-PET/CT, which did not reveal any FAP expression in the liver lesions, but increased FAP expression was observed in the soft tissue mass of the mesenteric root. Consequently, the pathology of the biopsy taken from the nodule in the right breast was revised, and a diagnosis of grade 2 NET was established. The benefit of FAPI-PET/CT on NETs has been previously investigated. Further prospective studies are required to establish the role of FAPI-PET/CT in NET management.
PubMed: 38949561
DOI: 10.4274/mirt.galenos.2024.89106 -
Minerva Urology and Nephrology Jul 2024The risk of recurrence for non-muscle invasive bladder cancer (NMIBC) is high, and the current methods of predicting it rely on clinical and histopathological markers....
BACKGROUND
The risk of recurrence for non-muscle invasive bladder cancer (NMIBC) is high, and the current methods of predicting it rely on clinical and histopathological markers. Personalized risk assessment can be improved by including new prognostic biomarkers. Our research explores the potential of urinary metabolomics to predict cancer recurrence in NMIBC patients within three years.
METHODS
Fifty NMIBC patients were included in the study. Urine samples were collected at diagnosis and before TUR-BT. After three years, patients were classified as relapsed or non-relapsed. An NMR-based metabolomics approach was used to measure the concentration of 44 metabolites in the urine of these patients at the time of their diagnosis. This method provides a comprehensive view of many urinary compounds potentially valuable for discriminating relapsing from non-relapsing patients. The measured metabolic profiles were analyzed through multivariate analysis, probability ROC curves, and Mann-Whitney tests.
RESULTS
Seven metabolites were involved in NMIBC recurrence prediction. We interpret their alteration as the consequence of three main events: gut dysbiosis, systemic inflammation, and immune inhibition. Since these compounds have already been proposed for BC diagnosis, what distinguishes their role as prognostic or diagnostic is the grade of their alteration. Limitations: small sample size; further research to confirm urinary compounds' correlation with physiological processes.
CONCLUSIONS
This study exploits urinary metabolic profiles to predict NMIBC recurrence. Specific metabolites are found to be significantly related to cancer relapse. The study highlights the grade of inflammation, immune suppression, and gut dysbiosis in predicting cancer recurrence.
PubMed: 38949559
DOI: 10.23736/S2724-6051.24.05747-1 -
Molecular Imaging and Radionuclide... Jun 2024We present the case of a patient with newly diagnosed high-risk prostate cancer. The patient underwent nephrectomy for renal cell carcinoma (RCC) in 2009. The...
We present the case of a patient with newly diagnosed high-risk prostate cancer. The patient underwent nephrectomy for renal cell carcinoma (RCC) in 2009. The prostate-specific membrane antigen (PSMA) scan revealed a primary tumor with seminal vessel involvement, PSMA-positive regional lymph nodes, several nodular lung lesions with mild PSMA uptake, PSMA-positive mediastinal lymph nodes, and a PSMA-positive mass in the pancreatic head. Ultrasound-guided biopsy was performed for the pancreatic lesions revealing metastasis from a RCC. Simultaneous treatment for prostate cancer and metastatic RCC was initiated. To separate metastatic sites for both primaries, we attempted to use fluorodeoxyglucose positron emission tomography/computed tomography, which was moderately positive for the pancreatic mass but not for the other locations. RCC is a Ga PSMA-positive tumor; the synchronous combination of RCC with prostate cancer can be confusing and requires more complex clinical interpretation.
PubMed: 38949477
DOI: 10.4274/mirt.galenos.2023.90582 -
Internal Medicine Journal Jul 2024This study surveyed South Australian medical oncologists to capture their perceptions, willingness to participate and perceived barriers and motivations to participation...
This study surveyed South Australian medical oncologists to capture their perceptions, willingness to participate and perceived barriers and motivations to participation in voluntary assisted dying (VAD) activities. Approximately 70% of surveyed medical oncologists reported familiarity with VAD legislation. Less than half of physicians (39.1%) reported willingness to participate in any VAD activities, and the rate of conscientious objection was 22%. The top barriers to participation were lack of time and uncertainty given no prior experience. These results demonstrate both a low rate of conscientious objection and a low rate of willingness to participate at the point of VAD implementation in South Australia, and identify barriers to participation that are largely logistical.
PubMed: 38949456
DOI: 10.1111/imj.16448 -
Journal of Visualized Experiments : JoVE Jun 2024Extensive studies have proven the promise of chimeric antigen receptor T (CAR-T) cell therapy in treating hematological malignancies. However, treating solid tumors...
Extensive studies have proven the promise of chimeric antigen receptor T (CAR-T) cell therapy in treating hematological malignancies. However, treating solid tumors remains challenging, as exemplified by the safety concerns that arise when CAR-T cells attack normal cells expressing the target antigens. Researchers have explored various approaches to enhance the tumor selectivity of CAR-T cell therapy. One representative strategy along this line is the construction of hypoxia-sensitive CAR-T cells, which are designed by fusing an oxygen-dependent degradation domain to the CAR moiety and are strategized to attain high CAR expression only in a hypoxic environment-the tumor microenvironment (TME). This paper presents a protocol for the generation of such CAR-T cells and their functional characterization, including methods to analyze the changes in CAR expression and killing capacity in response to different oxygen levels established by a mobile incubator chamber. The constructed CAR-T cells are anticipated to demonstrate CAR expression and cytotoxicity in an oxygen-sensitive manner, thus supporting their capability to distinguish between hypoxic TME and normoxic normal tissues for selective activation.
Topics: Receptors, Chimeric Antigen; Humans; T-Lymphocytes; Immunotherapy, Adoptive; Cell Hypoxia; Tumor Microenvironment
PubMed: 38949315
DOI: 10.3791/66697 -
Journal of Visualized Experiments : JoVE Jun 2024Conventional static cold storage (SCS) exacerbates ischemic injury in the DCD liver, leading to severe complications for transplant recipients. To address this issue,...
Conventional static cold storage (SCS) exacerbates ischemic injury in the DCD liver, leading to severe complications for transplant recipients. To address this issue, clinical application of MP technology for donor liver preservation is underway. Simultaneously, efforts are focused on the development of various MP instruments, validated through relevant animal model experiments. Effective large animal trials play a pivotal role in clinical applications. However, challenges persist in the ex vivo preservation of DCD livers and the transplantation procedure in pigs. These hurdles encompass addressing the prolonged preservation of donor livers, conducting viability tests, alleviating ischemic injuries, and shortening the anhepatic phase. The use of a variable temperature-controlled MP device facilitates the prolonged preservation of DCD livers through sequential Dual Hypothermic Oxygenated Machine Perfusion (DHOPE) and Normothermic Machine Perfusion (NMP) modes. This protocol enhances the porcine OLTx model by improving the quality of DCD livers, optimizing the anastomosis technique, and reducing the duration of the anhepatic phase.
Topics: Animals; Liver Transplantation; Organ Preservation; Swine; Perfusion; Liver
PubMed: 38949305
DOI: 10.3791/65879 -
Liver International : Official Journal... Jul 2024We examined the impact of a co-diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes (T2D) on patient outcomes.
BACKGROUND AND AIMS
We examined the impact of a co-diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes (T2D) on patient outcomes.
METHODS
Using TriNetX, a global federated research network (n = 114 million), we undertook two retrospective cohort studies, using time-to-event analysis. Analysis 1 compared MASLD with T2D to MASLD alone; analysis 2 compared T2D with MASLD to T2D alone. Propensity score matching using greedy nearest neighbour (calliper .1) balanced the cohorts (1:1) for significant covariates. Primary outcomes were cardiovascular, liver, diabetes-related, and cancer events over 5 years.
RESULTS
Analysis 1 (n = 95 275): a co-diagnosis of T2D significantly increased the risk of ischaemic heart disease (IHD) (HR 1.39; CI: 1.34, 1.44), ischaemic stroke (HR 1.45; CI: 1.35, 1.56), heart failure (HR 1.42; CI: 1.36, 1.49), atrial fibrillation (HR 1.09; CI: 1.03, 1.16), hepatocellular carcinoma (HR 1.96; CI: 1.69, 2.27), pancreatic cancer (HR 1.25; CI: 1.06, 1.48) and liver-related complications over 5 years from MASLD diagnosis. Analysis 2 (n = 15 208): a co-diagnosis of MASLD significantly increased risk of all-cause mortality (HR 1.11; CI: 1.02, 1.22), IHD (HR 1.181; CI: 1.08, 1.29), hepatocellular (HR 50.31; CI: 6.94, 364.72), pancreatic (HR 1.78; CI: 1.12, 2.84), breast (HR 1.43; CI: 1.09, 1.88) and renal cancer (HR 2.01; CI: 1.24, 3.26), and diabetic neuropathy (HR 1.17; CI: 1.09, 1.27) over 5 years from metformin initiation.
CONCLUSIONS
T2D significantly potentiates the risk of cardiovascular, malignancy and liver-related outcomes in people with MASLD. The effect of MASLD on people with T2D, although less dramatic, still potentiated risk of death, IHD, malignancy and peripheral neuropathy.
PubMed: 38949295
DOI: 10.1111/liv.16016 -
Journal of Cellular Physiology Jul 2024Cancer-associated fibroblasts (CAFs) are a major cellular component in the tumor microenvironment and have been shown to exhibit protumorigenic effects in...
Cancer-associated fibroblasts-secreted exosomal miR-92a-3p promotes tumor growth and stemness in hepatocellular carcinoma through activation of Wnt/β-catenin signaling pathway by suppressing AXIN1.
Cancer-associated fibroblasts (CAFs) are a major cellular component in the tumor microenvironment and have been shown to exhibit protumorigenic effects in hepatocellular carcinoma (HCC). This study aimed to delve into the mechanisms underlying the tumor-promoting effects of CAFs in HCC. Small RNA sequencing was conducted to screen differential expressed microRNAs in exosomes derived from CAFs and normal fibroblasts (NFs). The miR-92a-3p expression was then measured using reverse transcriptase quantitative real-time PCR in CAFs, NFs, CAFs-derived exosomes (CAFs-Exo), and NF-derived exosomes (NFs-Exo). Compared to NFs or NF-Exo, CAFs and CAFs-Exo significantly promoted HCC cell proliferation, migration, and stemness. Additionally, compared to NFs or NF-Exo, miR-92a-3p level was notably higher in CAFs and CAFs-Exo, respectively. Exosomal miR-92a-3p was found to enhance HCC cell proliferation, migration, and stemness. Meanwhile, AXIN1 was targeted by miR-92a-3p. Exosomal miR-92a-3p could activate β-catenin/CD44 signaling in HCC cells by inhibiting AXIN1 messenger RNA. Furthermore, in vivo studies verified that exosomal miR-92a-3p notably promoted tumor growth and stemness through targeting AXIN1/β-catenin axis. Collectively, CAFs secreted exosomal miR-92a-3p was capable of promoting growth and stemness in HCC through activation of Wnt/β-catenin signaling pathway by suppressing AXIN1. Therefore, targeting CAFs-derived miR-92a-3p may be a potential strategy for treating HCC.
PubMed: 38949237
DOI: 10.1002/jcp.31344 -
Cancer Medicine Jul 2024Distress during SARS-CoV-2 outbreak affected also cancer patients' well-being. Aim of this study was to investigate patient' reactions and behavior (flexible-adaptive...
The emotional states and associated behavioral responses (flexible-adaptive behaviors vs. inflexible-maladaptive behaviors) of cancer patients during the SARS-CoV-2 outbreak: A multi-center cross-sectional study in Italy.
OBJECTIVE
Distress during SARS-CoV-2 outbreak affected also cancer patients' well-being. Aim of this study was to investigate patient' reactions and behavior (flexible-adaptive vs. inflexible-maladaptive) during the SARS-CoV-2 outbreak.
METHODS
A cross-sectional survey was designed with a self-report questionnaire, "the ImpACT questionnaire," developed for the study. Regression analysis was performed on data.
RESULTS
Four hundred and forty five cancer patients from 17 Italian regions participated in the study. 79.8% of participants were female (mean age of 58 years). 92.6% of participants reported feeling vulnerable to COVID-19 contagion; 75.6% reported helpless, 62.7% sad, 60.4% anxious, and 52.0% anger. Avoidance of thinking about coronavirus is the principal maladaptive behavior that emerged. Participants who reported feeling anxious were more likely to have fear of staff being infected with COVID-19 (OR = 3.01; 95% CI = 1.49-6.30) and to have disrupted sleep due to worry (OR = 2.42; 95% CI = 1.23-4.83). Younger participants reported more anxiety (OR = 0.97; 95% CI = 0.94-1.00); men reported feeling calm more than women (OR = 2.60; 95% CI = 1.27-5.43).
CONCLUSIONS
Majority of cancer patients reported serious concerns regarding SARS-CoV-2 infection; reliable information and psychological support must be offers to respond to these needs.
Topics: Humans; COVID-19; Female; Male; Cross-Sectional Studies; Middle Aged; Italy; Neoplasms; SARS-CoV-2; Aged; Anxiety; Adaptation, Psychological; Emotions; Surveys and Questionnaires; Adult; Fear
PubMed: 38949180
DOI: 10.1002/cam4.7442 -
Cancer Medicine Jul 2024The current guidelines for managing screen-detected pulmonary nodules offer rule-based recommendations for immediate diagnostic work-up or follow-up at intervals of 3,...
BACKGROUND
The current guidelines for managing screen-detected pulmonary nodules offer rule-based recommendations for immediate diagnostic work-up or follow-up at intervals of 3, 6, or 12 months. Customized visit plans are lacking.
PURPOSE
To develop individualized screening schedules using reinforcement learning (RL) and evaluate the effectiveness of RL-based policy models.
METHODS
Using a nested case-control design, we retrospectively identified 308 patients with cancer who had positive screening results in at least two screening rounds in the National Lung Screening Trial. We established a control group that included cancer-free patients with nodules, matched (1:1) according to the year of cancer diagnosis. By generating 10,164 sequence decision episodes, we trained RL-based policy models, incorporating nodule diameter alone, combined with nodule appearance (attenuation and margin) and/or patient information (age, sex, smoking status, pack-years, and family history). We calculated rates of misdiagnosis, missed diagnosis, and delayed diagnosis, and compared the performance of RL-based policy models with rule-based follow-up protocols (National Comprehensive Cancer Network guideline; China Guideline for the Screening and Early Detection of Lung Cancer).
RESULTS
We identified significant interactions between certain variables (e.g., nodule shape and patient smoking pack-years, beyond those considered in guideline protocols) and the selection of follow-up testing intervals, thereby impacting the quality of the decision sequence. In validation, one RL-based policy model achieved rates of 12.3% for misdiagnosis, 9.7% for missed diagnosis, and 11.7% for delayed diagnosis. Compared with the two rule-based protocols, the three best-performing RL-based policy models consistently demonstrated optimal performance for specific patient subgroups based on disease characteristics (benign or malignant), nodule phenotypes (size, shape, and attenuation), and individual attributes.
CONCLUSIONS
This study highlights the potential of using an RL-based approach that is both clinically interpretable and performance-robust to develop personalized lung cancer screening schedules. Our findings present opportunities for enhancing the current cancer screening system.
Topics: Humans; Lung Neoplasms; Male; Female; Early Detection of Cancer; Middle Aged; Case-Control Studies; Aged; Retrospective Studies; Tomography, X-Ray Computed; Reinforcement, Psychology; Precision Medicine
PubMed: 38949177
DOI: 10.1002/cam4.7436