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Cureus Nov 2023Collecting duct carcinoma (CDC) is an aggressive renal malignancy with limited diagnostic and therapeutic consensus. We report a case of a 69-year-old male with CDC and...
Collecting duct carcinoma (CDC) is an aggressive renal malignancy with limited diagnostic and therapeutic consensus. We report a case of a 69-year-old male with CDC and extensive coagulative necrosis who presented with lower extremity swelling, abdominal distention, and an enlarged left kidney causing grade IV hydronephrosis. Initial treatment with a left percutaneous nephrostomy was followed by clinical deterioration and a diagnosis of emphysematous pyelonephritis. Pathological examination of drainage material revealed extensive coagulative necrosis and was suggestive of a necrotic neoplasm. Subsequent left nephrectomy confirmed CDC with high-grade features, stromal desmoplasia, and extensive coagulative necrosis. Immunohistochemistry studies supported the diagnosis. This study highlights the diagnostic complexity of CDC and emphasizes the need for accurate reporting of atypical presentations. CDC remains a formidable clinical entity with limited treatment options and poor outcomes. Further research is essential to enhance our understanding and management of this rare and aggressive renal malignancy.
PubMed: 38957193
DOI: 10.7759/cureus.49295 -
Molecular Oncology Jul 2024Small cell lung cancer (SCLC) is a highly aggressive cancer with a dismal 5-year survival of < 7%, despite the addition of immunotherapy to first-line chemotherapy.... (Review)
Review
Small cell lung cancer (SCLC) is a highly aggressive cancer with a dismal 5-year survival of < 7%, despite the addition of immunotherapy to first-line chemotherapy. Specific tumor biomarkers, such as delta-like ligand 3 (DLL3) and schlafen11 (SLFN11), may enable the selection of more efficacious, novel immunomodulating targeted treatments like bispecific T-cell engaging monoclonal antibodies (tarlatamab) and chemotherapy with PARP inhibitors. However, obtaining a tissue biopsy sample can be challenging in SCLC. Circulating tumor cells (CTCs) have the potential to provide molecular insights into a patient's cancer through a "simple" blood test. CTCs have been studied for their prognostic ability in SCLC; however, their value in guiding treatment decisions is yet to be elucidated. This review explores novel and promising targeted therapies in SCLC, summarizes current knowledge of CTCs in SCLC, and discusses how CTCs can be utilized for precision medicine.
PubMed: 38956984
DOI: 10.1002/1878-0261.13696 -
Acta Dermato-venereologica Jul 2024Tumour budding (TB) correlates with increased local invasion in various neoplasms. Certain basal cell carcinomas (BCCs) exhibit local aggressiveness. Detecting adverse...
Tumour budding (TB) correlates with increased local invasion in various neoplasms. Certain basal cell carcinomas (BCCs) exhibit local aggressiveness. Detecting adverse prognostic factors in partial biopsies could aid in identifying cases with heightened local risk. The absolute number of TB (≤ 3 tumour cells) in excision specimens of 271 infiltrative BCCs (0: absent; 1: 1-2 foci; 2: ≥ 3 foci; 3: ≥ 10 foci), the histopathological subtype and depth of infiltration, perineural invasion, and other histological features were evaluated. A significant correlation was found between TB and both depth of infiltration (rho 0.445, p < 0.001) and perineural invasion (p = 0.009). In the multivariate analysis of depth and perineural invasion (multiple regression, stepwise), TB was identified as a significant covariate together with diameter, inflammation, and perineural invasion for the former, and depth for the latter. Conversely, no correlation existed between the WHO histological subtypes (infiltrating, sclerosing, and micronodular), and depth of infiltration or perineural invasion. This study demonstrates the value of TB as a biomarker for local invasiveness in BCC. In routine practice, a count of ≥ 3 TB foci in lesions incompletely excised or with narrow tumour-free surgical margins would be a straightforward and reproducible method to guide BCC treatment.
Topics: Humans; Carcinoma, Basal Cell; Skin Neoplasms; Neoplasm Invasiveness; Male; Female; Aged; Predictive Value of Tests; Middle Aged; Biopsy; Risk Factors; Multivariate Analysis; Aged, 80 and over; Adult; Retrospective Studies
PubMed: 38956962
DOI: 10.2340/actadv.v104.40172 -
CNS & Neurological Disorders Drug... Jul 2024Gliomas are the most frequent, heterogeneous group of tumors arising from glial cells, characterized by difficult monitoring, poor prognosis, and fatality. Tissue biopsy...
BACKGROUND
Gliomas are the most frequent, heterogeneous group of tumors arising from glial cells, characterized by difficult monitoring, poor prognosis, and fatality. Tissue biopsy is an established procedure for tumor cell sampling that aids diagnosis, tumor grading, and prediction of prognosis.
MATERIALS AND METHODS
We studied and compared the levels of liquid biopsy markers in patients with different grades of glioma. Also, we tried to prove the potential association between glioma and specific blood group antigens.
RESULTS
78 patients were found, among whom the maximum percentage with glioblastoma had blood group O+ (53.8%). The second highest frequency had blood group A+ (20.4%), followed by B+ (9.0%) and A- (5.1%), and the least with O-. Liquid biopsy biomarkers included Alanine Aminotransferase (ALT), Lactate Dehydrogenase (LDH), lymphocytes, Urea, Alkaline phosphatase (AST), Neutrophils, and C-Reactive Protein (CRP). The levels of all the components increased significantly with the severity of the glioma, with maximum levels seen in glioblastoma (grade IV), followed by grade III and grade II, respectively.
CONCLUSION
Gliomas have significant clinical challenges due to their progression with heterogeneous nature and aggressive behavior. A liquid biopsy is a non-invasive approach that aids in setting up the status of the patient and figuring out the tumor grade; therefore, it may show diagnostic and prognostic utility. Additionally, our study provides evidence to prove the role of ABO blood group antigens in the development of glioma. However, future clinical research on liquid biopsy will improve the sensitivity and specificity of these tests and confirm their clinical usefulness to guide treatment approaches.
.PubMed: 38956913
DOI: 10.2174/0118715273306577240612053957 -
Journal of Cardiothoracic Surgery Jul 2024The burden of metastatic lymph node (LN) stations might reflect a distinct N subcategory with a more aggressive biology and behaviour than the traditional N...
OBJECTIVES
The burden of metastatic lymph node (LN) stations might reflect a distinct N subcategory with a more aggressive biology and behaviour than the traditional N classification.
METHODS
Between 2008 and 2018, we analyzed 1236 patients with pN1/2 lung cancer. Survival was analyzed based on LN station metastasis, determining the optimal threshold for the number of metastatic LN stations that provided additional prognostic information. N prognostic subgrouping was performed using thresholds for the number of metastatic LN stations with the maximum chi-square log-rank value, and validated at each pT-stage.
RESULTS
Survival showed stepwise statistical deterioration with an increase in the number of metastatic LN stations., Threshold values for the number of metastatic LN stations were determined and N prognostic subgroupswas created as sN-alpha; one LN station metastases (n = 632), sN-beta; two-three LN stations metastases (n = 505), and sN-gamma; ≥4 LN stations metastasis (n = 99). The 5-year survival rate was 57.7% for sN-alpha, 39.2% for sN-beta, and 12.7% for sN-gamma (chi-square log rank = 97.906, p < 0.001). A clear tendency of survival deterioration was observed from sN-alpha to sN-gamma in the same pT stage, except for pT4 stage. Multivariate analysis showed that age (p < 0.001), sex (p = 0.002), tumour histology (p < 0.001), IASLC-proposed N subclassification (p < 0.001), and sN prognostic subgroups (p < 0.001) were independent risk factors for survival.
CONCLUSION
The burden of metastatic LN stations is an independent prognostic factor for survival in patients with lung cancer. It could provide additional prognostic information to the N classification.
Topics: Humans; Lung Neoplasms; Male; Female; Prognosis; Lymphatic Metastasis; Middle Aged; Aged; Lymph Nodes; Retrospective Studies; Pneumonectomy; Neoplasm Staging; Survival Rate; Lymph Node Excision; Adult; Aged, 80 and over
PubMed: 38956613
DOI: 10.1186/s13019-024-02874-w -
Molecular Brain Jul 2024Glioblastoma (GBM) is an aggressive nervous system tumor with a poor prognosis. Although, surgery, radiation therapy, and chemotherapy are the current standard protocol... (Review)
Review
Glioblastoma (GBM) is an aggressive nervous system tumor with a poor prognosis. Although, surgery, radiation therapy, and chemotherapy are the current standard protocol for GBM patients, there is still a poor prognosis in these patients. Temozolomide (TMZ) as a first-line therapeutic agent in GBM can easily cross from the blood-brain barrier to inhibit tumor cell proliferation. However, there is a high rate of TMZ resistance in GBM patients. Since, there are limited therapeutic choices for GBM patients who develop TMZ resistance; it is required to clarify the molecular mechanisms of chemo resistance to introduce the novel therapeutic targets. MicroRNAs (miRNAs) regulate chemo resistance through regulation of drug metabolism, absorption, DNA repair, apoptosis, and cell cycle. In the present review we discussed the role of miRNAs in TMZ response of GBM cells. It has been reported that miRNAs mainly induced TMZ sensitivity by regulation of signaling pathways and autophagy in GBM cells. Therefore, miRNAs can be used as the reliable diagnostic/prognostic markers in GBM patients. They can also be used as the therapeutic targets to improve the TMZ response in GBM cells.
Topics: Humans; Temozolomide; Glioblastoma; MicroRNAs; Drug Resistance, Neoplasm; Brain Neoplasms; Animals; Dacarbazine; Autophagy; Gene Expression Regulation, Neoplastic
PubMed: 38956588
DOI: 10.1186/s13041-024-01113-6 -
Scientific Reports Jul 2024The systemic immune-inflammation index (SII), a metric reflecting systemic inflammatory response and immune activation, remains underexplored concerning its correlation...
The systemic immune-inflammation index (SII), a metric reflecting systemic inflammatory response and immune activation, remains underexplored concerning its correlation with mortality among rheumatoid arthritis (RA) patients. This study aimed to delineate the association between SII and both all-cause and cardiovascular mortality within the cohort of American adults diagnosed with RA, utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2018. The investigation extracted data from NHANES cycles between 1999 and 2018, identifying RA patients through questionnaire responses. The SII was computed based on complete blood counts, employing the formula: (platelets × neutrophils) / lymphocytes. The optimal SII cutoff value for significant survival outcomes was determined using maximally selected rank statistics. Multivariable Cox proportional hazards models assessed the relationship between SII levels and mortality (all-cause and cardiovascular) among RA patients, with subgroup analyses examining potential modifications by clinical confounders. Additionally, restricted cubic spline (RCS) analyses were conducted to explore the linearity of the SII-mortality association. The study encompassed 2070 American adults with RA, among whom 287 exhibited a higher SII (≥ 919.75) and 1783 a lower SII (< 919.75). Over a median follow-up duration of 108 months, 602 participants died. After adjustments for demographic, socioeconomic, and lifestyle variables, a higher SII was associated with a 1.48-fold increased risk of all-cause mortality (hazard ratio [HR] = 1.48, 95% confidence interval [CI] 1.21-1.81, P < 0.001) and a 1.51-fold increased risk of cardiovascular mortality (HR = 1.51, 95% CI 1.04-2.18, P = 0.030) compared to a lower SII. Kaplan-Meier analyses corroborated significantly reduced survival rates within the higher SII cohort for both all-cause and cardiovascular mortality (P < 0.0001 and P = 0.0004). RCS analyses confirmed a positive nonlinear relationship between SII and mortality rates. In conclusion, the SII offers a straightforward indicator of the equilibrium between detrimental innate inflammation and beneficial adaptive immunity. Our investigation, utilizing a comprehensive and nationally representative sample, reveals that elevated SII levels independently forecast a greater risk of mortality from all causes, as well as cardiovascular-specific mortality, in individuals suffering from RA. These insights underscore the clinical relevance of the SII as an affordable and readily accessible biomarker. Its incorporation into regular clinical practice could significantly enhance the precision of risk assessment and forecasting for patients with RA, facilitating more tailored and effective management strategies. Specifically, patients with high SII levels could be identified for more stringent cardiovascular risk management, including closer monitoring, lifestyle interventions, and aggressive pharmacological treatments to mitigate their increased risk of mortality.
Topics: Humans; Arthritis, Rheumatoid; Male; Female; Cardiovascular Diseases; Middle Aged; Inflammation; Nutrition Surveys; Aged; Adult; Cause of Death; Proportional Hazards Models; Risk Factors
PubMed: 38956376
DOI: 10.1038/s41598-024-66152-4 -
Scientific Reports Jul 2024Laboratory mice are typically housed in "shoebox" cages with limited opportunities to engage in natural behaviour. Temporary access to environments with increased space...
Laboratory mice are typically housed in "shoebox" cages with limited opportunities to engage in natural behaviour. Temporary access to environments with increased space and complexity (playpens) may improve mouse welfare. Previous work by our group has shown that mice are motivated to access and use these environments, but it is unknown how other aspects of welfare are impacted. Female C57BL/6J, BALB/cJ, and DBA/2J mice (n = 21; 7 mice per strain) were housed in mixed-strain trios and given temporary access to a large playpen with their cage mates three times per week. Control mice (n = 21; 7 mice per strain) remained in their home cages. Home cage behaviour (development of stereotypic behaviour over time, aggression following cage-changing) and anxiety tests were used to assess how playpen access impacted welfare. Contrary to our predictions, we found increased time spent performing stereotypies in playpen mice; this difference may be related to negative emotional states, increased motivation to escape the home cage, or active coping strategies. Playpen access resulted in strain-dependent improvements in aggression and some measures of anxiety. Aggression was lower for C57BL/6J mice in the playpen treatment following cage changing than it was for C57BL/6J control mice, while playpen mice, and particularly the C57BL/6J strain, spent more time in the center of the open field test and produced fewer fecal boli during anxiety testing, supporting other research showing that strain differences play an important role in behaviour and stress resiliency.
Topics: Animals; Animal Welfare; Mice; Female; Mice, Inbred C57BL; Housing, Animal; Behavior, Animal; Aggression; Anxiety; Mice, Inbred BALB C; Mice, Inbred DBA; Stereotyped Behavior
PubMed: 38956228
DOI: 10.1038/s41598-024-65480-9 -
Annals of Surgical Oncology Jul 2024Grade 1/2 PanNETs are mostly managed similarly, typically without any adjunct treatment with the belief that their overall metastasis rate is low. In oncology...
Subgrading of G2 Pancreatic Neuroendocrine Tumors as 2A (Ki67 3% to < 10%) Versus 2B (10% to ≤ 20%) Identifies Behaviorally Distinct Subsets in Keeping with the Evolving Management Protocols.
BACKGROUND
Grade 1/2 PanNETs are mostly managed similarly, typically without any adjunct treatment with the belief that their overall metastasis rate is low. In oncology literature, Ki67-index of 10% is increasingly being used as the cutoff in stratifying patients to different protocols, although there are no systematic pathology-based studies supporting this approach.
METHODS
Ki67-index was correlated with clinicopathologic parameters in 190 resected PanNETs. A validation cohort (n = 145) was separately analyzed.
RESULTS
In initial cohort, maximally selected rank statistics method revealed 12% to be the discriminatory cutoff (close to 10% rule of thumb). G2b cases had liver/distant metastasis rate of almost threefold higher than that of G2a and showed significantly higher frequency of all histopathologic signs of aggressiveness (tumor size, perineural/vascular invasion, infiltrative growth pattern, lymph node metastasis). In validation cohort, these figures were as striking. When all cases were analyzed together, compared with G1, the G2b category had nine times higher liver/distant metastasis rate (6.1 vs. 58.5%; p < 0.001) and three times higher lymph node metastasis rate (20.5 vs. 65.1%; p < 0.001).
CONCLUSIONS
G2b PanNETs act very similar to G3, supporting management protocols that regard them as potential therapy candidates. Concerning local management, metastatic behavior in G2b cases indicate they may not be as amenable for conservative approaches, such as watchful waiting or enucleation. This substaging should be considered into diagnostic guidelines, and clinical trials need to be devised to determine the more appropriate management protocols for G2b (10% to ≤ 20%) group, which shows liver/distant metastasis in more than half of the cases, which at minimum warrants closer follow-up.
PubMed: 38955993
DOI: 10.1245/s10434-024-15632-y -
Brazilian Journal of Microbiology :... Jul 2024To describe the clinical-laboratory profile and analyze the factors associated with the severity of COVID-19.
OBJECTIVE
To describe the clinical-laboratory profile and analyze the factors associated with the severity of COVID-19.
METHODS
A prospective cohort study involving patients with COVID-19 admitted to a tertiary hospital in Recife, Brazil. All cases were confirmed by RT-PCR and classified according to severity criteria. A descriptive statistical analysis of the population's characteristics was conducted. Risk factors associated with the outcome of the case according to severity were analyzed by calculating the odds ratio (OR) using the general equation estimation (GEE) model.
RESULTS
Among the 75 cases included, 64% were female, and 62.7% were aged 65 years or older. The median length of stay was 9 days (6 - 14). Hypertension (65.3%) and Diabetes Mellitus (36%) were the most frequent comorbidities. Severe forms of COVID-19 constituted 41.3% of the sample. The factors associated with severity were a history of asthma (OR=4.58, 95%CI:1.13 - 18.7), report of anorexia (OR=1, 12, 95%CI:1.01-1.24), and laboratory changes that included elevated platelets (OR=1.00, 95% CI:1.00-1.01), elevated D'Dimer (OR=1, 26, 95% CI:1.04-1.52), elevated aspartate aminotransferase (OR=1.00, 95% CI:1.00-1.01), and gamma-glutamyl transferase (OR=1.22, IC95 %:0.98-1.51), hypernatremia (OR=1.31, 95%CI:1.12-1.52), and hyperkalemia (OR=1.21, 95% CI:1.04-1.41).
CONCLUSION
Multisystemic involvement with a tendency for thrombophilia, electrolyte disturbances, and hepatic aggression, reflected by laboratory changes, were factors associated with the severity of COVID-19.
PubMed: 38955981
DOI: 10.1007/s42770-024-01382-2