Poor Prognostic Indicator Research Articles

Multi-omics analysis deciphers intercellular communication regulating oxidative stress to promote oral squamous cell carcinoma progression

Oral squamous cell carcinoma (OSCC) is a common malignant tumor in the head and neck, associated with high recurrence and poor prognosis. We performed an integrated analysis of single-cell RNA and spatial transcriptomic data from cancerous and normal tissues to create a comprehensive atlas of epithelial cells and cancer-associated fibroblasts (CAFs). Our findings show that AKR1C3+ epithelial cells, located at the tumor’s stromal front, exhibit significant copy number variation and poor prognostic indicators, suggesting a role in tumor invasion. We also identified a distinct group of early-stage CAFs (named OSCC_Normal, characterized by ADH1B+, MFAP4+, and PLA2G2A+) that interact with AKR1C3+ cells, where OSCC_Normal may inhibit the FOXO1 redox switch in these epithelial cells via the IGF1/IGF1R pathway, causing oxidative stress overload. Conversely, AKR1C3+ cells use ITGA6/ITGB4 receptor to counteract the effects of OSCC_Normal, promoting cancer invasion. This study unveils complex interactions within the OSCC tumor microenvironment.

ERO1A levels are a prognostic indicator in EGFR mutated non small cell lung cancer

We have identified endoplasmic reticulum oxidoreductase 1 alpha (ERO1A) as a poor prognostic indicator in epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (EGFRMUT-NSCLC). In addition, comparison of high versus low ERO1A expression among cohorts of EGFRMUT-NSCLC primary samples revealed that ERO1A expression correlated with increased expression of proteins that regulate secretion. Using the CPTAC proteomic data set in lung adenocarcinoma we found that high ERO1A protein expression correlated with both extracellular matrix and matrix modifying enzymes. In this report, we found that ablating ERO1A expression was a determinant of clonogenicity, tumor sphere formation, spheroid growth and growth in vivo, as well as response to Osimertinib. We validated that ERO1A-knockout EGFRMUT-LUAD cell lines demonstrated a reduction in secretion of both laminin gamma 2 (LAMC2) and the collagen modifying enzyme lysyl oxidase-like 2 (LOXL2). Our work supports the role of ERO1A in modulating the tumor microenvironment that is likely to contribute to tumor progression.

HOXA9 and CD163 potentiate pancreatic ductal adenocarcinoma progression

BackgroundThe role of HOXA9 requires investigations in pancreatic ductal adenocarcinoma (PDAC) as HOXA9 inhibitors are being developed. HOXA9 might attract CD163 expressed tumor associated macrophages (TAM) and could affect PDAC prognosis. This work aims to study the expression and relevance of HOXA9 and CD163 in PDAC progression.Materials and methodsSelected 98 PDAC and 98 adjacent non tumor tissues as a control group were immunostained with HOXA9 and CD163 antibodies.ResultsPDAC displayed highly significant higher HOXA9 staining intensity, percent and H score values than control group. HOXA9 staining of PDAC cases showed significant associations with poor prognostic indicators including larger tumor size, higher grade and advanced stage. PDAC showed highly significant differences regarding CD163 macrophage-specific staining intensity, percent and H score values than control group. CD163 showed significant higher expressions with larger tumor size, higher histological grade and advanced stage group. HOXA9 staining in PDAC showed highly significant direct correlations with CD163 positive macrophages. Follow up of PDAC cases revealed that high median H score of HOXA9 and CD163 were significantly associated with worse overall survival. CD163 was an independent prognostic marker of worse survival.ConclusionsIn conclusion, HOXA9 could potentiate PDAC progression by stimulating CD163 expressed TAM attraction in tumors. HOXA9 and CD163 could participate in PDAC therapy. HOXA9 and CD163 could be predictors of worse prognosis and shorter survival in PDAC.

Evaluation of Circulating Tumor DNA and Carcinoembryonic Antigen Levels and Relationship with Clinicopathological Risk Factors and Prognostic Indices in Colorectal Cancer Patients

Objective: Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. ctDNA has emerged as a promising biomarker for CRC management, offering real-time insights into tumor burden and genetic mutations. This study investigates the correlation between CEA levels, ctDNA, clinicopathological factors, and treatment outcomes in early and advanced CRC patients. Methods: The study retrospectively analyzed data from CRC patients, including early-stage disease and metastatic disease. ctDNA levels, demographic data, and clinical parameters such as CEA, inflammatory indexes, and tumor characteristics were evaluated to determine correlations with treatment outcomes. Results: The study included 20 patients, with 60% diagnosed at the metastatic stage. The study found no statistically significant correlation between ctDNA levels and disease stage, recurrence, or overall survival. While CEA and ctDNA levels were measured, they did not demonstrate a significant relationship with treatment outcomes. Notably, ctDNA levels were higher in metastatic patients, though this was not statistically significant. Conclusion: Despite its potential, the integration of ctDNA as a routine biomarker in CRC care faces challenges, including variability in measurement techniques and cost-effectiveness. However, ctDNA's ability to guide personalized treatment strategies and monitor disease recurrence holds promise. The study's findings align with previous research, suggesting ctDNA as a poor prognostic indicator, though further research is needed. ctDNA represents a significant advance in CRC management, offering non-invasive, real-time insights into tumor dynamics. Ongoing research is expected to solidify its role in personalized treatment planning, potentially leading to more effective and tailored therapies for CRC patients.

Perinephric Extramedullary Disease in Multiple Myeloma.

Extramedullary disease represents an aggressive form of multiple myeloma occurring outside the skeleton and is a poor prognostic indicator. Extramedullary disease most commonly involves the skin, muscle, pleura, lymph nodes, liver, and central nervous system. Infrequently, extramedullary disease can involve the kidneys or perirenal space. We present 3 cases of perirenal involvement of extramedullary disease on 18 F-FDG PET/CT confirmed with tissue sampling as plasma cell infiltration. Within the limitation of physiologic activity in the kidneys due to 18 F-FDG excretion, close consideration is essential when evaluating multiple myeloma patients for genitourinary involvement as it can resemble other malignancies, hemorrhage, or renal injury.

Lymphomas of the submandibular gland: a nationwide cohort study.

This study explores the epidemiology, incidence, and survival outcomes associated with lymphomas of the submandibular gland (SMG) and examines the influence of autoimmune diseases on these parameters. This retrospective nationwide cohort study analysed data from patients diagnosed with SMG lymphomas in Denmark between 2000 and 2020. Information was extracted from medical records, the National Pathology Register, and the Danish Lymphoma Database. Survival analyses were conducted using Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models, focusing on lymphoma subtypes and autoimmune diseases. The cohort consisted of 101 patients with a lymphoma diagnosis and involvement of the SMG. Large B-cell lymphoma (LBCL) was diagnosed in 33 cases (32.7%), follicular lymphoma (FL) in 29 cases (28.7%), extranodal marginal zone lymphoma (EMZL) in 27 cases (26.7%), and 12 cases (11.9%) with other subtypes. EMZL had a significantly longer overall survival (OS) compared to other subtypes, with a median OS of 12.4 years (95% CI 11.2-12.4) vs. 8.4 years (95% CI 6.0-12.2). EMZL and FL showed favourable 5-year OS rates of 95% and 89%, respectively. LBCL had a 5-year OS rate of 65%. Age over 60 significantly negatively impacted OS. Traditional poor prognostic indicators did not significantly affect OS. A notable association between EMZL and autoimmune diseases was observed, particularly with Sjögren's syndrome, indicated by an increased relative risk of 2.67 (CI 95% 0.45-16.01). Lymphomas of the SMG are rare and have ambiguous clinical presentations. This study provides novel epidemiological, clinical, and prognostic information.

Epstein-Barr virus-positive, primary cutaneous marginal zone lymphoma, with transformation: Case report and review of the literature.

We report a patient with EBV positive PCMZL with subsequent transformation to plasmablastic lymphoma and review the literature for transformed PCMZL to assess clinical and pathologic characteristics. In the case we describe, the patient presented with multifocal PCMZL, developed large B cell transformation with plasmacytic differentiation, followed by plasmablastic transformation (PBL), and ultimately died of disease progression despite multiple lines of therapy. Past history was significant for psoriatic arthritis (multiple prior lines of immunomodulatory therapy). The lymphomas and non-involved bone marrow share the same somatic DNMT3A and TET2 mutations, suggesting clonal relatedness and an association with clonal hematopoiesis (CH). Eighteen cases complied the cohort (seventeen cases from the literature and the case reported herein). Nearly half of the eighteen cases of PCMZL with transformation died of progressive disease (44%). Transformed cases were more commonly seen in patients with >2 sites at initial diagnosis. EBV was assessed in 5 patients, 3 were positive (all died of disease). Two patients with NGS studies demonstrated TET2 and DNMT3A mutations. Transformation of EBV positive PCMZL appears to be a poor prognostic indicator, with our reported case being the first well defined case transformed to PBL, suspected to arise from myeloid-CH.

Prognosis of isolated tumor cells and use of molecular classification in early stage endometrioid endometrial cancer

ObjectiveWe assessed the prognosis and molecular subtypes of early stage endometrioid endometrial cancer with isolated tumor cells within sentinel lymph nodes (SLNs) compared with node negative disease.MethodsPatients diagnosed with stage...

Differential effect of tumor budding on the benefit of adjuvant chemotherapy in stage II colorectal cancer: a retrospective observational study.

Tumor budding (TB) has been shown to be a poor prognostic indicator after colorectal cancer (CRC) surgery. The aim of the present study is to evaluate the predictive role of morphological features (e.g., the number, structure, and location of tumor buds, and their reaction with the extracellular mesenchyme) in postoperative adjuvant chemotherapy in surgically resectable stage II CRC. Between 2016 and 2019, 336 patients with stage II CRC who underwent radical surgery were enrolled in this study. TB status was determined according to the criteria adopted at the 2016 International Tumor Budding Consensus Conference (ITBCC). We retrospectively recorded all the clinical and pathological data and assessed the effect of different types of TB status on patients' recurrence-free survival (RFS) and overall survival (OS). Of the 336 patients, 173, 88, and 75 were budding grade 1 (BD1), BD2, and BD3, respectively. The 5-year RFS rates were 84.6%, 81.2%, and 68.0% (P=0.01), and the 5-year OS rates were 91.0%, 83.3%, and 76.2% (P=0.007) in BD1, BD2, and BD3, respectively. TB grade was strongly associated with vascular invasion status and mucinous adenocarcinoma, and BD3 was detected in 51.7% of patients with positive vascular invasion. The multivariate analysis showed that only age, perineural invasion, and TB grade [BD2 vs. BD1, hazard ratio (HR) =1.468, 95% confidence interval (CI): 0.703-3.063, P=0.30; BD3 vs. BD1, HR =2.310, 95% CI: 1.154-4.625, P=0.01] had an independent effect on RFS. In addition, the Kaplan-Meier curve analysis showed that BD3 patients had the worst RFS (P=0.01). The OS of the adjuvant chemotherapy group was significantly improved compared to that of the surgery-only group in the BD1/2 patients (HR =0.278, 95% CI: 0.114-0.676, P=0.005) but not in the BD3 patients with significant interaction (Pinteraction=0.03). Our results indicate that TB could play a subsidiary role in selecting stage II CRC patients who could achieve a favorable prognosis with chemotherapy.

Pathological PCI as a prognostic marker of survival after neoadjuvant chemotherapy in patients undergoing interval cytoreduction with or without HIPEC in FIGO stage IIIC high grade serous ovarian cancer.

To determine the best possible value of pathological PCI (pPCI) as a prognostic marker for survival in high-grade serous epithelial ovarian cancer patients in patients treated with neoadjuvant chemotherapy and interval cytoreductive surgery. All patients with FIGO stage IIIC high-grade serous ovarian carcinoma were included. Receiver operating curves (ROC) were used to determine the best possible score for pPCI in predicting survival. Survival curves were calculated using the Kaplan-Meier test, and factors affecting survival were compared using the log-rank test. From January 2018 to January 2024, 171 patients who underwent interval cytoreductive surgery were included. Complete cytoreduction was achieved in 88% of the patients. ROC curves determined a (pPCI) cut-off value of 8 as the best possible score for predicting survival with a sensitivity of 82% and specificity of 67% (Youden's Index = 0.60). pPCI with a cut-off value of 8 showed improved OS (p = 0.002) and DFS, (p = 0.001) in both univariate and multivariate analyses. Following interval cytoreductive surgery, despite optimal complete cytoreductive surgery, a pathological PCI of 8 is a poor prognostic indicator of survival and may serve as a surrogate clinical marker for guiding clinicians in adjuvant treatment, especially in resource-driven settings in the real world.

Lactate as an early prognostic indicator in yellow phosphorus rodenticide-induced acute hepatic failure: a retrospective observational study in a tertiary care hospital

Introduction Acute hepatic failure due to yellow phosphorus rodenticide ingestion is often lethal. This study aimed to analyze demographic characteristics and prognostic indicators, focusing on hyperlactataemia as a potential early indicator of mortality in patients poisoned with yellow phosphorus rodenticide. Materials and methods This was a retrospective study of 96 patients poisoned with a yellow phosphorus-containing rodenticide (Ratol paste, which contains 3% yellow phosphorus). We examined demographic details, clinical symptoms, and biochemical markers to identify prognostic indicators. Results Demographics were similar among survivors and non-survivors. Mortality (36.5%) correlated with a higher ingested dose and treatment delays, with a mean (±SD) of 5.26 ± 2.2 survival days among those who died. Symptoms, including gastrointestinal and neurological features, typically appeared 48 h after ingestion. Non-survivors developed increased aminotransferase activities (74.3%), prolonged prothrombin time (65.7%), and hyperbilirubinaemia (65.7%) during hospitalization, significantly more commonly compared to survivors (P < 0.0001). Hyperlactataemia (lactate concentration >2 mmol/L) was present in 97.1% of non-survivors, with increased serial lactate concentrations observed in 88.6%. The median (interquartile range) admission lactate concentration among non-survivors was 4.6 mmol/L (3.36–7.53 mmol/L), and their peak median (interquartile range) lactate concentration was 6.1 mmol/L (8.74–10.6 mmol/L). In non-survivors, an increased lactate concentration preceded increased aminotransferase activities and prolonged prothrombin time. Logistic regression and receiver operating characteristic curve analysis confirmed that a 24 h lactate concentration ≥2.67 mmol/L predicted death with 94.3% sensitivity and 91.8% specificity. Discussion The majority of patients who ingest yellow phosphorus remain asymptomatic initially and typically present to hospital following the onset of gastrointestinal symptoms, usually a day later. As progression to death occurs within a week of yellow phosphorus ingestion in most cases, determining prognosis as early as possible enables swift referral to a liver transplant centre. Based on our study, a 24 h lactate concentration ≥2.67 mmol/L appears to be an early prognostic indicator of death. In another study, a lactate concentration >5.8 mmol/L was found to be a poor prognostic indicator. Conclusions Hyperlactataemia on admission and increased serial lactate concentrations appear to be early poor prognostic signs in patients with yellow phosphorus-induced liver failure.

Pneumothorax as a Poor Prognostic Indicator in COVID-19 in Turkey: A Propensity Score Matching Analysis.

Spontaneous pneumothorax in COVID-19 occurs infrequently but in up to 15% of patients dependent on mechanical ventilation (MV). Pneumothorax-related deaths account for 1% of all COVID-19-related deaths. To determine factors associated with pneumothorax in COVID-19 patients and the effect of pneumothorax on early survival. This was a retrospective study of 4799 COVID-19-positive hospitalized patients. The groups were homogenized using propensity score matching (PSM) in two groups comprising 67 COVID-19 patients each. The prevalence of pneumothorax was determined. Multiple logistic regression was used to determine factors associated with pneumothorax. P value < 0.05 was taken as significant. The prevalence of pneumothorax in COVID-19 patients was 1.6%. Lung disease, comorbidities, and oxygen support, which were significantly different between the two groups before PSM, were homogenized after PSM. In a univariate analysis, symptom duration (P ˂ 0.001), neutrophilia (P ˂ 0.001), lymphopenia (P ˂ 0.001), neutrophil-lymphocyte ratio (P = 0.003), ferritin levels (P = 0.012), D-dimer levels (P = 0.011), MV support (P ˂ 0.001), antibiotherapy (P ˂ 0.001), length of hospital stay (P = 0.009), and death (P = 0.002) differed significantly between the groups. Pneumothorax had a significant negative effect on survival (32.8% vs. 59.7%, P = 0.01). In a multivariate regression model, factors associated with pneumothorax were duration of symptoms (Adjusted Odds ratio (AOR) 1.68; 95% Confidence Interval (CI): 1.26-2.25; P = 0.001), mechanical ventilation (AOR 23.92; 95% CI: 4.12-138.72; P = <0.001), dual antibiotics (AOR 8.28; 95% CI: 1.56-43.86; P = 0.013), neutrophilia (AOR: 1.08; 95% CI: 1.02-1.14; P = 0.011), and lymphopenia (AOR: 0.92; 95% CI: 0.86-0.90; P = 0.022). The presence of pneumothorax was associated with poor survival in COVID-19 patients. Patients with a prolonged time from symptom onset to treatment and those dependent on mechanical ventilation in intensive care were in the high risk group for the development of pneumothorax.

Transarterial chemoembolization for renal cell carcinoma patients with liver metastases in the era of immunotherapy: A case series

Treatment for renal cell carcinoma (RCC) has changed rapidly in the past decade with the widespread implementation of immune checkpoint inhibitors (ICIs) as first-line therapy in metastatic disease. The presence of liver metastases is a poor prognostic indicator but also has the potential to be a target for localized therapy. However, there is limited knowledge on the dynamics and long-term effects of combining liver-directed transarterial chemoembolization (TACE) with ICI therapy. We identified four patients with metastatic RCC (mRCC) and liver metastases who were treated concurrently with ICIs and TACE to metastatic liver lesions from our institutional database. We assessed treatment radiological responses and toxicity in this cohort. Liver-directed TACE with concurrent ICI was associated with radiological response or stabilization in all the liver lesions in the four patients in this cohort with a median time to locoregional liver metastasis progression-free survival of 8.3 months (range 6.0–11.1). The concurrent administration of ICI therapy and TACE to liver lesions was well tolerated with no new safety signals and no immune-related toxicities. Combining TACE with ICI in patients with mRCC showed promising response with limited toxicity. Future studies are warranted to clarify treatment timing and validate benefits.

Internal Mammary Lymphadenopathy Does Not Impact Oncologic Outcomes in Patients Treated with Neoadjuvant Chemotherapy: Results from the I-SPY2 Clinical Trial.

Internal mammary lymphadenopathy (IML) plays a role in breast cancer stage and prognosis. We aimed to evaluate method of IML detection, how IML impacts response to neoadjuvant chemotherapy (NAC), and oncologic outcomes. We evaluated patients enrolled in the I-SPY-2 clinical trial from 2010 to 2022. We captured the radiographic method of IML detection (magnetic resonance imaging [MRI], positron emission tomography/computed tomography [PET/CT], or both) and compared patients with IML with those without. Rates of locoregional recurrence (LRR), distant recurrence (DR) and event-free survival (EFS) were compared by bivariate analysis. Of 2095 patients, 198 (9.5%) had IML reported on pretreatment imaging. The method of IML detection was 154 (77.8%) MRI only, 11 (5.6%) PET/CT only, and 33 (16.7%) both. Factors associated with IML were younger age (p=0.001), larger tumors (p<0.001), and higher tumor grade (p=0.027). Pathologic complete response (pCR) was slightly higher in the IML group (41.4% vs. 34.0%; p=0.03). There was no difference in breast or axillary surgery (p=0.41 and p=0.16), however IML patients were more likely to undergo radiation (68.2% vs. 54.1%; p<0.001). With a median follow up of 3.72 years (range 0.4-10.2), there was no difference between IM+ versus IM- in LRR (5.6% vs. 3.8%; p=0.25), DR (9.1% vs. 7.9%; p=0.58), or EFS (61.6% vs. 57.2%; p=0.48). This was true for patients with and without pCR. In this large cohort of patients treated with NAC, outcomes were not negatively impacted by IML. We demonstrated that IML influences treatment selection but is not a poor prognostic indicator when treated with modern NAC and multidisciplinary disease management.

LncRNA FAM30A Predicts Adverse Prognosis and Regulates Cellular Processes in Colorectal Cancer via Modulating miR-21-3p.

Colorectal cancer (CRC) is a prevalent gastrointestinal cancer with high incidence and mortality rate. lncRNAs could regulate the expression of miRNAs and further affect cancer development. Previous research has suggested that FAM30A is involved in various cancer. We aimed to investigate the function of FAM30A in the prognosis of CRC and its underlying molecular mechanisms. Matched tissues were collected from 107 CRC patients. FAM30A was measured by quantitative real-time transcription polymerase chain reaction and its clinical significance was evaluated by its correlation with patients' prognosis and clinicopathological features. Furthermore, the dual luciferase reporter assays were employed to assess the interactions between FAM30A and miR-21-3p and to evaluate the role of miR-21-3p in regulating the tumor suppressor effects of FAM30A. Cell proliferation and metastasis were evaluated by the Transwell assay and cell counting kit-8 assay. FAM30A level was markedly decreased in CRC tissues (P <.001). A prominent association was observed in FAM30A with tumor- node-metastasis stage (P = .022), carcinoembryonic antigen (P = .027), and differentiation (P = .043) of CRC patients. The lower the FAM30A level was associated with the lower the survival rate of the CRC patients (log rank P = .034). FAM30A could negatively modulate miR-21-3p (P <.001), and the overexpression of FAM30A significantly suppressed CRC cell proliferation and metastasis (P <.001). The suppressive function of FAM30A overexpression was mediated by miR-21-3p. FAM30A can be considered a poor prognostic indicator in CRC. Decreased FAM30A can promote the proliferation and metastasis of CRC cells by negatively regulating miR-21-3p.

FKBP3, a poor prognostic indicator, promotes the progression of LUAD via regulating ferroptosis and immune infiltration.

Ferroptosis was reported to possess the therapeutic potentials in various human cancers. In the present study, we explored the expression, clinical significance and the molecular mechanism of FK506 binding protein 3 (FKBP3) in the progression of lung adenocarcinoma (LUAD). Cox regression was performed to obtain the prognosis related to differentially expressed genes (DEGs) in LUAD datasets from TCGA. We also downloaded the ferroptosis-related gene datasets from GeneCards. Venn diagram was performed to find the intersecting genes and FKBP3 was selected as the targeted gene by analyzing the diagnostic and prognostic values of Top10 intersecting genes. Moreover, univariate and multivariate analyses were performed to evaluate the association between clinicopathological factors and survival rates. GO/KEGG and GSEA analysis was performed to explore the function of FKBP3 in LUAD progression. Protein-protein interaction (PPI) network was performed via STRING database and the top10 hub genes were selected. Finally, the relationship between FKBP3 and immune infiltration was explored by ssGSEA analysis. Firstly, 184 genes associated with the prognosis of LUAD and ferroptosis were obtained. FKBP3 was found to be significantly associated with a poor overall survival rate of LUAD patients. Immunohistochemical staining results showed that FKBP3 was highly located in cytoplasm and membrane of cells in LUAD tissues. PPI network analysis results showed that HDAC1, YY1, HDAC2, MTOR, PSMA3, PIN1, NCL, C14orf166, PIN4, and LARP6 were the top10 hub genes. Furthermore, spearman analysis results showed that the expression of FKBP3 was positively correlated with the abundance of Th2 cells and T helper cells. High level of FKBP3 was associated with poor prognostic outcomes of LUAD patients, which also inhibited immune infiltration in LUAD tissues. Additionally, FKBP3 was involved in regulating the ferroptosis process in LUAD patients. Thus, FKBP3 possessed the tumor promotion role might be involving in regulating ferroptosis and immune infiltration in LUAD progression.

Prognostic significance of necrosis in ampullary carcinomas

Background/aimsNecrosis is an important pathological feature that reflects high malignancy potential in tumors such as hepatocellular carcinoma and renal cell carcinoma. We aimed to elucidate the prognostic impact of necrosis in ampullary carcinomas.Materials and methodsWe reviewed 101 consecutive cases of ampullary carcinoma for tumor necrosis, types of necrosis, macroscopic and microscopic histopathological subtypes, lymphatic-vascular-perineural invasions, and other histopathological parameters.ResultsTumor necrosis was present in 19 (18.8%) cases and was identified as an independent poor prognostic indicator in multivariate survival analysis (p = 0.029).ConclusionThe presence of necrosis in ampullary carcinomas is directly related to vascular and perineural invasion and is a poor prognostic indicator independent of tumor stage. Including the presence of necrosis in the pathology reports of ampullary carcinomas will facilitate risk stratification.

Visual Intratumor Heterogeneity and Breast Tumor Progression.

High intratumoral heterogeneity is thought to be a poor prognostic indicator. However, the source of heterogeneity may also be important, as genomic heterogeneity is not always reflected in histologic or 'visual' heterogeneity. We aimed to develop a predictor of histologic heterogeneity and evaluate its association with outcomes and molecular heterogeneity. We used VGG16 to train an image classifier to identify unique, patient-specific visual features in 1655 breast tumors (5907 core images) from the Carolina Breast Cancer Study (CBCS). Extracted features for images, as well as the epithelial and stromal image components, were hierarchically clustered, and visual heterogeneity was defined as a greater distance between images from the same patient. We assessed the association between visual heterogeneity, clinical features, and DNA-based molecular heterogeneity using generalized linear models, and we used Cox models to estimate the association between visual heterogeneity and tumor recurrence. Basal-like and ER-negative tumors were more likely to have low visual heterogeneity, as were the tumors from younger and Black women. Less heterogeneous tumors had a higher risk of recurrence (hazard ratio = 1.62, 95% confidence interval = 1.22-2.16), and were more likely to come from patients whose tumors were comprised of only one subclone or had a TP53 mutation. Associations were similar regardless of whether the image was based on stroma, epithelium, or both. Histologic heterogeneity adds complementary information to commonly used molecular indicators, with low heterogeneity predicting worse outcomes. Future work integrating multiple sources of heterogeneity may provide a more comprehensive understanding of tumor progression.

FUNCTIONAL OUTCOMES OF DORSAL BRIDGE PLATING FOR LISFRANC INJURIES WITH ROUTINE METALWORK RETENTION: A MAJOR TRAUMA CENTRE EXPERIENCE

BackgroundAnatomical reduction of unstable Lisfranc injuries is crucial. Evidence as to the best methods of surgical stabilization remains sparse, with small patient numbers a particular issue. Dorsal bridge plating offers rigid stability and joint preservation.The primary aim of this study was to assess the medium-term functional outcomes for patients treated with this technique at our centre. Additionally, we review for risk factors that influence outcomes.Methods85 patients who underwent open reduction and dorsal bridge plate fixation of unstable Lisfranc injuries between January 2014 and January 2019 were identified. Metalwork was not routinely removed. A retrospective review of case notes was conducted. The Manchester-Oxford Foot Questionnaire summary index (MOXFQ-Index) was the primary outcome measure, collected at final follow-up, with a minimum follow-up of 24 months. The American Orthopedic Foot and Ankle Society (AOFAS) midfoot scale, complications, and all-cause re-operation rates were secondary outcome measures. Univariate and multivariate analyses were used to identify risk factors associated with poorer outcomes.ResultsMean follow-up 40.8 months (24–72). Mean MOXFQ-Index 27.0 (SD 7.1). Mean AOFAS score 72.6 (SD 11.6). 48/85 patients had injury patterns that included an intra-articular fracture and this was associated with poorer outcomes, with worse MOXFQ and AOFAS scores (both p &lt; 0.001). 18 patients (21%) required the removal of metalwork for either prominence or stiffness. Female patients were more likely to require metalwork removal (OR 3.89, 95% CI 1.27 to 12.0, p = 0.02). Eight patients (9%) required secondary arthrodesis.ConclusionsThis is the largest series of Lisfranc injuries treated with dorsal bridge plate fixation reported to date and the only to routinely retain metalwork. The technique is safe and effective. The presence of an intraarticular fracture is a poor prognostic indicator. Metalwork removal is more likely to be needed in female patients but routine removal may not be essential.

In vivo cisplatin-resistant neuroblastoma metastatic model reveals tumour necrosis factor receptor superfamily member 4 (TNFRSF4) as an independent prognostic factor of survival in neuroblastoma.

Neuroblastoma is the most common solid extracranial tumour in children. Despite major advances in available therapies, children with drug-resistant and/or recurrent neuroblastoma have a dismal outlook with 5-year survival rates of less than 20%. Therefore, tackling relapsed tumour biology by developing and characterising clinically relevant models is a priority in finding targetable vulnerability in neuroblastoma. Using matched cisplatin-sensitive KellyLuc and resistant KellyCis83Luc cell lines, we developed a cisplatin-resistant metastatic MYCN-amplified neuroblastoma model. The average number of metastases per mouse was significantly higher in the KellyCis83Luc group than in the KellyLuc group. The vast majority of sites were confirmed as having lymph node metastasis. Their stiffness characteristics of lymph node metastasis values were within the range reported for the patient samples. Targeted transcriptomic profiling of immuno-oncology genes identified tumour necrosis factor receptor superfamily member 4 (TNFRSF4) as a significantly dysregulated MYCN-independent gene. Importantly, differential TNFRSF4 expression was identified in tumour cells rather than lymphocytes. Low TNFRSF4 expression correlated with poor prognostic indicators in neuroblastoma, such as age at diagnosis, stage, and risk stratification and significantly associated with reduced probability of both event-free and overall survival in neuroblastoma. Therefore, TNFRSF4 Low expression is an independent prognostic factor of survival in neuroblastoma.