Malignant Group Research Articles

Characteristics and prognosis of small bowel tumors: A retrospective study

BACKGROUND Small bowel tumors (SBTs) are a heterogeneous group of difficult-to-diagnose tumors that account for 2%-5% of all gastrointestinal tumors. Single-balloon enteroscopy greatly enhances the diagnosis and treatment of SBTs. However, few epidemiological studies have been conducted in Taiwan to determine the clinical profile of SBTs. AIM To investigate the clinical characteristics, managements and prognosis of SBTs in a medical center in Taiwan. METHODS The study enrolled 51 patients aged 58.9 ± 8.8 years (range, 22-93) diagnosed with SBTs from November 2009 to July 2021. We retrospectively recorded clinical characteristics, indications, endoscopic findings, pathological results, management, and outcomes for further analysis. RESULTS A male preponderance was observed (56.8%). The most common indications were suspected small intestinal tumors (52.9%) and obscure gastrointestinal bleeding (39.2%). The most common tumor location was the ileum (41.2%). The performance of imaging studies (P = 0.004) and the types of findings (P = 0.005) differed significantly between malignant and benign SBTs. The most frequent imaging finding was a small intestinal mass (43.1%). The top three malignant tumor types were gastrointestinal stromal tumors (GISTs), adenocarcinomas, and lymphomas. Moreover, the proportions of benign and malignant tumors were 27.5% and 72.5%, respectively. The survival rates of patients with malignant tumors in the GIST and non-GIST groups differed significantly (P = 0.015). Kaplan–Meier survival analysis showed a significant difference in survival between patients in the malignant and benign groups (P = 0.04). All patients with lymphoma underwent chemotherapy (n = 7/8, 87.5%), whereas most patients with GISTs underwent surgery (n = 13/14, 92.8%). CONCLUSION Patients with GISTs have a significantly higher survival rate than those with other malignant SBTs. Therefore, a large-scale nationwide study is warranted to evaluate the population-based epidemiology of SBTs.

Prognosticators of Optic Nerve Imaging in Malignant Pseudotumor Cerebri Syndrome.

Pseudotumor cerebri (PTC) syndrome is a disorder of increased intracranial pressure, most commonly affecting overweight women of childbearing age. Malignant PTC (MPTC) is a rare presentation that involves rapidly worsening vision, often necessitating surgical intervention to prevent permanent vision loss. The goal of this study was to determine whether radiographic findings of PTC are predictive of MPTC and the final visual outcome. Charts of patients diagnosed with PTC based on the modified Dandy criteria were reviewed. Snellen best-corrected visual acuity (BCVA), automated perimetry mean deviation (APMD), and papilledema grade were documented from the initial and final follow-up examinations. The MRI images were read by 2 neuroradiologists blinded to the clinical diagnosis, and consensus findings were obtained. The patients were classified into malignant and nonmalignant PTC groups. Malignant was defined as BCVA ≤ 20/200 or APMD ≤ -7 dB, and acute onset of symptoms. The sensitivity and specificity of each MRI finding for detecting MPTC was determined. Generalized linear model with random effect and backward model selection was performed to identify which radiographic findings were predictive of final BCVA, APMD, and papilledema grade. Overall, 114 eyes (57 malignant/57 nonmalignant) were included. No MRI finding has both sensitivity and specificity for MPTC reaching 60%. The highest sensitivity (86%) was flattening of the posterior globes and unilateral or bilateral transverse sinus stenosis. The highest specificities were completely empty sella (86%), enhancement (84%), and diffusion restriction (81%) of the prelaminar optic nerves. The presence of vertical tortuosity of the optic nerves was predictive of better final BCVA (P = 0.003) and better final APMD (P = 0.011). While papilledema grade was higher in MPTC, no MRI finding was predictive of papilledema grade. No single MRI finding has both high sensitivity and specificity for diagnosing MPTC. Vertical tortuosity of the optic nerves may be predictive of better final BCVA and APMD.

Potential Use of Exosomal Non-Coding MicroRNAs in Leukemia Therapy: A Systematic Review

Leukemia is a heterogeneous group of hematological malignancies. Despite the enormous progress that has been made in the field of hemato-oncology in recent years, there are still many problems related to, among others, disease recurrence and drug resistance, which is why the search for ideal biomarkers with high clinical utility continues. Research shows that exosomes play a critical role in the biology of leukemia and are associated with the drug resistance, metastasis, and immune status of leukemias. Exosomes with their cargo of non-coding RNAs act as a kind of intermediary in intercellular communication and, at the same time, have the ability to manipulate the cell microenvironment and influence the reaction, proliferative, angiogenic, and migratory properties of cells. Exosomal ncRNAs (in particular, circRNAs and microRNAs) appear to be promising cell-free biomarkers for diagnostic, prognostic, and treatment monitoring of leukemias. This review examines the expression of exosomal ncRNAs in leukemias and their potential regulatory role in leukemia therapy but also in conditions such as disease relapse, drug resistance, metastasis, and immune status. Given the key role of ncRNAs in regulating gene networks and intracellular pathways through their ability to interact with DNA, transcripts, and proteins and identifying their specific target genes, defining potential functions and therapeutic strategies will provide valuable information.

Role of IFN-γ, IL-33, and IL-35 concentrations in tuberculous pleural effusion in diagnosis and analysis of the effectiveness of combined tests

This study examines the diagnostic utility of the combined interleukin-33 (IL-33), interferon-γ (IFN-γ), and interleukin-35 (IL-35) test in tuberculous pleural effusion. Forty patients with pleural effusion of unknown etiology admitted to the hospital between December 2020 and December 2023 were selected as the study group. The patients were further categorized into tuberculous (TB) (n = 20) and malignant (n = 20) groups on the basis of their relevant data, while sera from 20 healthy medical checkups were used as control group. Thoracentesis was used to collect pleural fluid, and after its collection, enzyme-linked immunosorbent assay was utilized to detect the concentration content of IL-35, IL-33, and IFN-γ in pleural fluid of patients with different types of diseases. Data processing and analysis were executed through SPSS23.0 software to plot the receiver operating characteristic curve and compare the area of the area under the line of each index. Adenosine deaminase level was statistically higher in TB group patients (59.91 U/L) than in malignant group (14.31 U/L) (P < .05). Pleural fluid lactate dehydrogenase levels did not differ significantly between the 2 groups (P > .05). T-SPOT test had a higher positive rate in the TB group (85%) and a lower positive rate in the malignant group (45%). The TB group exhibited significantly higher levels of IFN-γ expression than the malignant group (P < .05). The TB group had higher levels of IL-33 and IL-35 compared to the malignant group, with a statistically significant difference (P < .05). The TB group had a greater level of IL-33 (81.05 ± 10.11 pg/mL) than the cytology-positive group (39.37 ± 9.63 pg/mL), while the difference was not statistically significant (P > .05). The level of IL-35 (70.11 ± 10.37 pg/mL) in the TB group was lower than the level of IL-35 (72.13 ± 9.58 pg/mL) in the cytology-positive group. The specificity of the series of combined tests reached 95.81%, which was statistically superior to the single-factor test (P < .05). In the TB group, IFN-γ and IL-33, IFN-γ and IL-35, and IL-33 and IL-35 showed positive correlation. Combined determination of the concentration levels of IL-35, IL-33, and IFN-γ is of value in the diagnosis of tuberculous pleurisy.

Does de novo malignancy heighten the risk of rejection in kidney transplant recipients?

Abstract Background Malignancies are the third leading cause of death among kidney transplant recipients. These patients face increased mortality and challenges such as allograft loss and rejection, which may arise from surgical complications, changes in immunosuppressive therapy, or the use of chemotherapeutics. This study aims to examine the risk of allograft rejection and loss in kidney transplant recipients diagnosed with de novo malignancies. Methods This retrospective case-control study included adult kidney transplant patients from 1986 to 2020 who developed de novo malignancies. Each patient with a malignancy was matched with a control without malignancy using the nearest neighbor matching method. The outcomes measured were biopsy-confirmed allograft rejection, death-censored allograft loss, and overall mortality after the diagnosis of malignancy in the malignancy group and at any point in the control group. Results Of 2 750 records reviewed, 267 patients (9.7%) had biopsy-confirmed malignancies, with a median age of 60 years and 66.3% men. The median follow-up was 218 months. Kaplan-Meier analysis showed that the allograft rejection rates were lower in the malignancy group compared to the control group (26 vs. 60, p < 0.001). Overall mortality was higher in the malignancy group, although this difference was not statistically significant (104 vs. 73, p = 0.25). Death-censored allograft loss was similar between groups (22 vs. 32, p = 0.49). Chemotherapy and older recipient age were associated with reduced allograft rejection risk, as indicated by multivariable regression analysis. Conclusions In kidney transplant recipients with de novo malignancies, death with a functioning graft remains significant. However, allograft loss rates do not increase compared to those without malignancies, and rejection risk is reduced, especially in older and chemotherapy-treated patients. These findings suggest that managing immunosuppression reduction in this population may be appropriate, but further research is needed to determine optimal care strategies.

Comparison of clinical features of patients with or without severe gastrointestinal complications in aggressive gastrointestinal lymphomas.

Aggressive primary gastrointestinal non-Hodgkin lymphoma (PGINHL) is an uncommon and heterogeneous group of lymphoid malignancies, that differs from indolent lymphoma and has a high incidence of severe gastrointestinal complications (GICs). To investigate and compare the clinicopathological characteristics, treatments and outcomes in the GICs and No-GICs group with aggressive PGINHL. This retrospective analysis was performed on aggressive PGINHL patients between January 2013 and December 2021 at our hospital. The independent influence factors of GICs were obtained by univariate and multivariate Logistic regression analysis, the selected variables significantly related to GICs were selected as the final predictors to construct nomogram. Kaplan-Meier curves further analyzed the survival of patients in GICs and No-GICs groups. Survival analysis of GICs group was performed using Cox regression. We focused on 124 aggressive PGINHL cases, which had a relatively high incidence 48.4% (60/124 cases) of GICs, the most common histological type in GICs group was diffuse large B-cell lymphoma (DLBCL) (n = 49, 81.7%). In the GICs group, small intestine was the most common anatomic site of lesion (43.3%), followed by large intestine (31.7%), and then stomach and esophagus (25.0%). Multivariate Logistic regression analysis showed that the independent risk factors for GICs were the small intestine [odd ratio (OR) = 3.33; 95% confidence interval (CI): 1.47-9.41; P = 0.009), aggressive B-cell (OR = 0.09; 95%CI: 0.01-0.83; P = 0.033), maximum tumor diameter (OR = 1.25; 95%CI: 1.07-1.47; P = 0.005), invaded deep serous layer (OR = 3.38; 95%CI: 1.24-9.19; P = 0.017). We developed a nomogram to predict risk of GICs in aggressive PGINHL patients based on independent risk factors. The value of area under curve calculated by receiver operating characteristic curve was 0.815, and calibration curve and decision curve analysis further indicated that the prediction effect was superior. The majority of patients with GICs were given combination therapy (chemotherapy combined with surgery or radiation). Event-free survival and overall survival in GICs group were no worse than those in the No-GICs group. The complication rate of GICs in patients with aggressive PGINHL was relatively high, particularly in PGI-DLBCL. The independent risk factors for GICs were the small intestine, PGI-TNKL, bulky tumor, and depth of invasion. A combination treatment, involving surgery, improved survival in the GICs group.

Abstract 4135327: Long-term Bleeding Events after Percutaneous Coronary Intervention in Patients with Malignancy with and without Anticoagulant Therapy

Background: With the aging population, the prevalence of malignancies in patients undergoing percutaneous coronary intervention (PCI) is increasing. Active malignancy is increasingly recognized as a significant contributor to high bleeding risks. In cases where anticoagulant (AC) therapy is required, it becomes crucial to determine which is the optimal choice for cancer patients, direct oral anticoagulants (DOACs) or warfarin. The aim of this study was to investigate long-term bleeding events in patients with malignancy undergoing PCI. Methods: CLIDAS (Clinical Deep Data Accumulation System) is a multicenter database with 7 tertiary medical hospitals in Japan. This retrospective analysis using CLIDAS database included 6838 patients who underwent PCI during April 2014 and March 2020 and also who have completed 3-year follow-up were divided into two groups; No malignancy group (n=6155) and malignancy group (n=683). Malignancy was defined as patients with treatment history of malignancy. Furthermore, these patients were categorized into six groups based on the presence of malignancy and the type of AC therapy; 1) No malignancy without AC (n=5369), 2) No malignancy with DOAC (n=294), 3) No malignancy with warfarin (n=492), 4) Malignancy without AC (n=586), 5) Malignancy with DOAC (n=44), and 6) Malignancy with warfarin (n=53). The primary outcome was the incidence of bleeding events, defined according to the Global Use of Streptokinase and t-PA for Occluded Coronary Arteries classification of moderate and severe bleeding. Results: During the 3-year follow-up period, 260 (3.8%) patients experienced major bleeding events after PCI. Among these patients, 180 (3.4%) were in group 1, 9 (3.1%) in group 2, 33 (6.7%) in group 3, 27 (4.6%) in group 4, 2 (4.5%) in group 5, and 9 (17.0%) in group 6. Multivariate Cox regression analysis showed that patients in the malignancy group had a significantly higher rate of bleeding events (HR, 1.50; 95% CI, 1.03-2.18). Furthermore, only the malignancy with warfarin group showed a significantly higher rate of bleeding events compared to the no malignancy without AC group (HR, 4.03; 95% CI, 1.94-8.37). Conclusions: Patients with malignancies receiving warfarin were associated with a higher risk of bleeding events. DOACs may be a safer alternative to warfarin in reducing bleeding risk in this population.

Predicting malignancy in breast lesions: enhancing accuracy with fine-tuned convolutional neural network models

BackgroundThis study aims to explore the accuracy of Convolutional Neural Network (CNN) models in predicting malignancy in Dynamic Contrast-Enhanced Breast Magnetic Resonance Imaging (DCE-BMRI).MethodsA total of 273 benign lesions (benign group) and 274 malignant lesions (malignant group) were collected and randomly divided into a training set (246 benign and 245 malignant lesions) and a testing set (28 benign and 28 malignant lesions) in a 9:1 ratio. An additional 53 lesions from 53 patients were designated as the validation set. Five models—VGG16, VGG19, DenseNet201, ResNet50, and MobileNetV2—were evaluated. Model performance was assessed using accuracy (Ac) in the training and testing sets, and precision (Pr), recall (Rc), F1 score (F1), and area under the receiver operating characteristic curve (AUC) in the validation set.ResultsThe accuracy of VGG19 on the test set (0.96) is higher than that of VGG16 (0.91), DenseNet201 (0.91), ResNet50 (0.67), and MobileNetV2 (0.88). For the validation set, VGG19 achieved higher performance metrics (Pr 0.75, Rc 0.76, F1 0.73, AUC 0.76) compared to the other models, specifically VGG16 (Pr 0.73, Rc 0.75, F1 0.70, AUC 0.73), DenseNet201 (Pr 0.71, Rc 0.74, F1 0.69, AUC 0.71), ResNet50 (Pr 0.65, Rc 0.68, F1 0.60, AUC 0.65), and MobileNetV2 (Pr 0.73, Rc 0.75, F1 0.71, AUC 0.73). S4 model achieved higher performance metrics (Pr 0.89, Rc 0.88, F1 0.87, AUC 0.89) compared to the other four fine-tuned models, specifically S1 (Pr 0.75, Rc 0.76, F1 0.74, AUC 0.75), S2 (Pr 0.77, Rc 0.79, F1 0.75, AUC 0.77), S3 (Pr 0.76, Rc 0.76, F1 0.73, AUC 0.75), and S5 (Pr 0.77, Rc 0.79, F1 0.75, AUC 0.77). Additionally, S4 model showed the lowest loss value in the testing set. Notably, the AUC of S4 for BI-RADS 3 was 0.90 and for BI-RADS 4 was 0.86, both significantly higher than the 0.65 AUC for BI-RADS 5.ConclusionsThe S4 model we propose has demonstrated superior performance in predicting the likelihood of malignancy in DCE-BMRI, making it a promising candidate for clinical application in patients with breast diseases. However, further validation is essential, highlighting the need for additional data to confirm its efficacy.

The Role of Peripheral Blood Inflammation Indices in Patients with a Diagnosis of Endometrial Hyperplasia and Cancer

Purpose: Endometrial cancer (EC) is an important problem with its increasing incidence, especially in developed countries. There is no generally accepted screening program yet. The management of endometrial hyperplasia (EH), which is the most important risk factor, is complex because it is an invasive process. Methods: A retrospective study was conducted with a total of 72 patients. Patients between the ages of 35-65 with abnormal uterine bleeding, and increased endometrial thickness on transvaginal sonography were evaluated with pathology results. Sociodemographic characteristics of the patients and laboratory values at hospital admission were obtained from hospital records. White blood cells (WBC), neutrophils, lymphocytes, monocytes, eosinophils, basophils, and thrombocyte counts (x10⁹/L); plateletcrit (%), hemoglobin (Hb) (g/dL), and hematocrit (Htc) (%) values were recorded. Neutrophil lymphocyte ratio (NLR), monocyte lymphocyte ratio (MLR), and thrombocyte lymphocyte ratio (TLR) were obtained. Systemic immune-inflammation index (SII), systemic inflammation response index (SIRI) and pan-immune-inflammation value (PIV) were obtained. Results: Thirty-seven patients diagnosed with EH and 35 patients diagnosed with endometrial malignancy were included. The mean age of the EH was 45.5 years and the mean age of the malignant group was 50.5 years (p=0.027). The sociodemographic characteristics of the patients were found to be similar. There was no significant difference in complete blood count parameters between two groups. Mean values of NLR were 2.33 and 2.52 in EH and EC groups, respectively, p = 0.448. Mean values of MLR were 0.20 and 0.21, respectively, p = 0.498. Mean values of TLR were 0.16 and 0.15, respectively, p = 0.811. Mean values of SII were 720.1 and 812.4 (x10⁹/L), respectively, p = 0.456. Mean values of SIRI were 943.1 and 1095.6 (x10⁹/L), respectively, p = 0.257. Mean values of PIV were 312753.6 and 352975.1 (x10⁹/L), respectively, p = 0.514. Conclusion: Peripheral blood inflammation indices have recently been used in cancer diagnosis and follow-up. We did not find any statistically significant differences in the investigated parametrers between the EH and EC patient groups. Close follow-up is necessary in the presence of additional risk factors in women with EH.

Ultrasonography (USG) Evaluation among Patients with Biliary Obstruction in a Tertiary Care Center

Background: Biliary obstruction is a blockage in the bile ducts that prevents bile from flowing from the liver to the small intestine. Objectives: This study aimed to assess the efficacy of ultrasonography (USG) among patients with a blockage in the bile ducts as known as biliary obstruction. Methods: This was a prospective observational study conducted at the Department of Radiology and Imaging at Sir Salimulliah Medical College Hospital, Dhaka, Bangladesh. This study included patients with clinical suspicion of biliary obstruction who underwent USG. Characteristics of the obstruction were evaluated for both benign and malignant lesions through USG. The findings were then correlated with ERCP, histopathology, or surgery to calculate the diagnostic performance of the former two modalities. Results: Out of 145 patients, 63 were in the malignant group and 82 were in the benign group. The sensitivity, specificity, and accuracy of detecting the nature of obstruction by USG were 33%, 84%, and 48.9%, respectively. The overall diagnostic accuracy of USG in predicting the site of obstruction was 64.3%. Hydatid Cyst and the Main Pancreatic Duct Stricture were the most accurate findings of USG. Conclusions: USG should be the initial screening modality of choice for predicting the level and nature of obstruction in patients with a clinical suspicion of obstructive jaundice.

Single-cell sequencing applications in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous group of malignancies with poor prognosis. AML result from the proliferation of immature myeloid cells blocked at a variable stage of differentiation. Beyond inter-patient heterogeneity, AMLs are characterized by genetic and phenotypic intra-patient heterogeneity. Despite major advances in deciphering AML biology with bulk sequencing studies, pivotal questions remain unanswered. Analyses at the single-cell level could thus transform our understanding of these neoplasms. We review recent progresses in single-cell sequencing technologies from cell processing to bioinformatic pipelines. We next discuss how single-cell applications have helped understand the genetic and functional intra-leukemic heterogeneity, emphasizing aspects related to leukemic stem cells, clonal evolution and measurable residual disease (MRD) monitoring. We finally delineate how single-cell technologies could be implemented in routine clinical practice to improve patient management.

088. Transarterial Chemoembolization for Head and Neck Cancer: Case Series

Background: Head and neck cancers represent a diverse group of malignancies arising from the complex anatomy of the oral cavity, pharynx, larynx, nasal cavity, paranasal sinuses, and salivary glands. While traditional treatments like surgery, radiation, and chemotherapy remain mainstays, transarterial chemoembolization (TACE) has emerged as a potential therapeutic option, particularly for advanced or recurrent cases. We present two cases of head and neck cancer that receive TACE. Case: First Case: A 46 years old woman, with big lump on her left cheek. The patient was diagnosed with Basal Cell Adenocarcinoma T3N0M0 at right submandibular region. He has history of Docetaxel and Carboplatin 6 cycles chemotherapy. Second Case: A 51 years old man, complain a lump on his right tongue. The patient was diagnosed with Squamous Cell Carcinoma Well Differentiated at left glossus region. But no history of chemotherapy. Conclusion: Two cases with head and neck cancer in our center has good clinical outcome after receiving chemotherapy through TACE procedure. TACE is offering a targeted approach to deliver chemotherapy and induce tumor necrosis. Although, TACE is commonly used for liver cancer, but it demonstrates promising potential in improving outcomes for head and neck cancer patients in the future.

Bone marrow stromal cells enhance differentiation of acute myeloid leukemia induced by pyrimidine synthesis inhibitors.

Acute myeloid leukemia (AML) is a heterogeneous group of hematological malignancies characterized by differentiation arrest, high relapse rates, and poor survival. The bone marrow (BM) microenvironment is recognized as a critical mediator of drug resistance and a primary site responsible for AML relapse. Our previous study reported that 5-aminoimidazole-4-carboxamide ribonucleoside (AICAr) induces AML cell differentiation by inhibiting pyrimidine synthesis and activating Checkpoint kinase 1. Although the protective effect of BM stroma on leukemia cells in response to cytotoxic drugs is well-documented, its effect on AML differentiation remains less explored. In this study, we investigated the impact of stromal cell lines and primary mesenchymal stromal cells (MSCs) on AML cell line differentiation triggered by AICAr and brequinar, a known dihydroorotate dehydrogenase (DHODH) inhibitor. Our findings indicate that the mouse MS-5 stromal cell line, known for its cytoprotective effects, does not inhibit AML cell differentiation induced by pyrimidine synthesis inhibitors. Interestingly, AICAr caused morphological changes and growth arrest in MS-5 stromal cells via an AMP-activated protein kinase (AMPK)-dependent pathway. Human stromal cell lines HS-5 and HS-27, as well as primary MSCs isolated from patient bone marrow, were superior in promoting AML differentiation compared with mouse cells in response to AICAr and brequinar, with the inhibitors not significantly affecting the stromal cells themselves. In conclusion, our study highlights the supportive role of human BM MSCs in enhancing the differentiation effects of pyrimidine synthesis inhibitors on AML cells, suggesting that AML treatment strategies focusing on differentiation rather than cell killing may be successful in clinical settings.NEW & NOTEWORTHY This study is the first to demonstrate that human stromal cell lines and primary mesenchymal stromal cells from patients enhance the in vitro differentiation of acute myeloid leukemia (AML) cells induced by pyrimidine synthesis inhibitors, 5-aminoimidazole-4-carboxamide ribonucleoside (AICAr), and brequinar. Furthermore, this is the first report to show that AICAr affects mouse bone marrow stromal cells by activating AMP-activated protein kinase (AMPK) and that human stromal cells are superior to mouse cells for testing the effects of drugs on AML differentiation.

A Composite Index for Distinguishing Benign and Malignant Obstructive Jaundice.

To explore a more effective and practical comprehensive index for differentiating benign from malignant obstructive jaundice by analyzing the clinical data of patients with benign obstructive jaundice (BJ) group and malignant obstructive jaundice (MJ) group. A retrospective analysis was conducted on the clinical data of 339 patients with obstructive jaundice. The cases were divided into two data sets: training cohort and validation cohort. The cases were divided into two groups: malignant and benign obstructive jaundice group. Logistic regression analysis was used to build a prediction model for judging the nature of obstructive jaundice, and the prediction model was verified using the validation cohort. Multivariate analysis revealed that CEA, TBIL, and NLR were independent factors in malignant obstructive jaundice. A comprehensive index for differentiating benign from malignant obstructive jaundice was established based on these indicators. The sensitivity, specificity, and receiver operating characteristic curve of this model for differentiating benign from malignant obstructive jaundice were 79.57%, 93.26%, and 0.920, respectively. The prediction model based on the comprehensive index of CEA, TBIL, and NLR has a higher accuracy in differentiating malignant obstructive jaundice.

Treatment Considerations to Overcome the Barriers Associated with Skin Cancer Targeting

: Skin cancer is a prevalent and diverse group of malignancies affecting the skin, with three primary types: basal cell carcinoma, squamous cell carcinoma, and melanoma. Each subtype varies in terms of its histological origin, behavior, and potential for metastasis. Despite advances in treatment, skin cancer poses challenges due to biological barriers that hinder drug delivery, multidrug resistance mechanisms that limit treatment effectiveness, and the complex interplay of genetic alterations driving tumorigenesis. Current treatment strategies encompass a spectrum of approaches, including chemotherapies, immunotherapies, gene therapies, and innovative techniques such as photothermal therapy, iontophoretic therapy, electroporation therapy, microneedle array therapy, and nanotechnology- based treatments. The latter involves liposomes, niosomes, carbon nanotubes, dendrimers, hydrogels, and gold nanoparticles, all tailored to enhance drug delivery and therapeutic efficacy. Additionally, herbal drug-based therapy harnesses the potential of natural compounds to target various aspects of skin cancer progression. This review provides an overview of skin cancer types, challenges in treatment, and an extensive exploration of current therapeutic strategies, highlighting the everevolving landscape of innovative approaches that promise to transform how skin cancer is managed.

Targeted Therapy in Salivary Gland Cancer: Prevalence of a Selected Panel of Actionable Molecular Alterations in a German Tertiary Referral Center Patient Cohort.

Salivary gland carcinomas (SGC) are a heterogeneous group of malignancies, with 24 subtypes defined by the World Health Organization (WHO). The standard of therapy is surgical resection, with adjuvant radiotherapy in most cases. However, disease recurrence (R) or metastasis (M) is common and no active systemic therapies are currently available for RM-SGC resulting in a 5-year survival rate of only 20%. Overall, 55 SGC patients with seven different histological tumor subtypes were included in this study. formalin-fixed paraffin-embedded (FFPE) tissue samples were used for immunohistochemical (IHC) staining targeting HER2/neu, androgen receptor (AR), PD-L1, EGFR, panTRK, and TROP2. Fluorescence in situ hybridization (FISH) was performed for detecting HER2/neu amplifications and NTRK1/2/3 translocations in selected cases with relevant HER2/neu and panTRK protein expression, respectively. IHC and FISH results were correlated with patients' clinical and histopathological data. The overall prevalence of druggable molecular alterations, defined as an immunoreactive score ≥ 9 in at least one of the analyzed targets, was 54.4% with the highest percentage in oncocytic carcinomas (100%) and lowest percentage in acinic cell carcinomas (10%). EGFR overexpression proved to be the most common alteration (32.7% of cases) followed by overexpression of TROP2 (27.3%), AR (10.9%), HER2/neu (7.3%), PD-L1 (1.8%), and panTRK (1.8%). HER2/neu amplifications were found in 50% and NTRK translocations were found in 100% of all cases with elevated Her2/neu and panTRK protein expression, respectively. Our data indicate that targeted therapy using e.g., trastuzumab deruxtecan, bicalutamide, pembrolizumab, cetuximab, entrectinib or sacituzumab govitecan might be a promising option especially for a relevant subset of patients with RM-SGC not suitable for salvage surgery. However, evidence from clinical studies regarding response rates to these therapies remains sparse, which underlines the need of multicenter clinical trials.

GPRASP protein deficiency triggers lymphoproliferative disease by affecting B-cell differentiation.

Gprasp1 and Gprasp2 encode proteins that control the stability and cellular trafficking of CXCR4, a master regulator of hematopoiesis whose dynamic regulation is required for appropriate trafficking of B-cells in the germinal center (GC). Here, we report that Gprasp1 and Gprasp2-deficient B-cells accumulate in the GC and show transcriptional abnormalities, affecting the mechanisms controlling Aicda expression and exposing them to excessive somatic hypermutation. Consequently, about 30% of mice transplanted with Gprasp-deficient hematopoietic stem and progenitor cells developed a biologically aggressive and fatal B-cell hyperproliferative disease by 20-50 weeks posttransplant. Histological and molecular profiling reveal that Gprasp1- and Gprasp2-deficient neoplasms morphologically resemble human high-grade B-cell lymphomas of germinal center origin with shared morphologic features of both Burkitt Lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL), and molecular features consistent with DLBCL, as well as elevated mutational burden and heterogenous transcriptional and mutational signature. Thus, reduced Gprasp1 and Gprasp2 gene expression perturbs B-cell maturation and increases the risk of B-cell neoplasms of germinal center origin. As this model recapitulates the essential features of the heterogenous group of human hematopoietic malignancies, it could be a powerful tool to interrogate the mechanisms of lymphomagenesis for these cancers.

Baseline characteristics, management patterns and outcome in patients with pulmonary embolism and malignancy: Insights from a single-centre study

Abstract Background and aim The presence of malignancy is an important factor that increases the risk of venous thromboembolism. On the other hand, acute pulmonary embolism (PE) is one of the main causes of death in this setting. In this study, we evaluated the impact of active malignancy on the treatment choices, and short and long term clinical outcomes in patients with acute PE. Methods In this study conducted in a tertiary center, 872 acute PE patients (age 61.6±16.8 years, female 57.5 %) from different risk categories were treated with thrombolytic, anticoagulant and catheter-based therapies in accordance with currently available acute PE guidelines. The population was retrospectively analyzed and divided into two groups according to the presence of active malignancy. Results Active malignancy was documented in 129 (14.8 %) patients. In the groups with and without malignancy, the proportions of low-, intermediate-low-, intermediate-high-, and high-risk PE patients were 3.1 % vs. 15.6 %, 17.8 % vs. 16.7 %, 60.5 % vs. 60 %, and 18.6 % vs. 7.7 %, respectively (p<0.001). While the two groups did not differ in terms of echocardiographic and computed tomographic pulmonary angiography (CTPA) characteristics, the presence of contraindications for thrombolytic were more frequent in the malignancy group (22.5% vs. 10.9%, p<0.001). Ultrasound-assisted thrombolysis (USAT), rheolytic thrombectomy (RT), systemic thrombolysis (ST) and anticoagulation-alone (AC) therapies were noted in 27.3 %, 6.4 %, 6.4 % and 49.7 % of overall PE patients. The RT and AC therapies were more frequent in PE patients with malignancy whereas ST and USAT were more frequently used in the absence of malignancy. Notably, lytic dosages and treatment durations in USAT and ST protocols were comparable between malignant and non-malignant PE cohorts. Regardless of the presence of malignancy and the treatment modality chosen, significant improvements were achieved in the clinical, echocardiographic and CTPA measures of the PE severity (p<0.001 for all). Major and minor bleeding rates were also similar in both groups, while in-hospital and, as expected, long-term mortality were higher in the malignancy cohort. Active malignancy and PESI score were found to be independent predictors for composite end-point of 60-day mortality and PE-related rehospitalization (adjusted odds ratio (OR): 2.43; 95 % CI: 1.32 - 4.47, p=0.04) and (OR: 1.02; 95 % CI: 1.01-1.01, p<0.001), respectively. Malignancy (OR: 3.5, 95 % CI: 2.15-5.75, p< 0.001) and chronic obstructive pulmonary disease (OR: 2.51, 95 % CI: 1.35-4.68, p< 0.003) were independent predictors of long-term mortality. Conclusion Concomitant malignancy adversely affects both short- and long-term outcomes in patients with acute PE. Although these patients are more vulnerable, it is possible to achieve satisfactory treatment success with acceptable bleeding rates with the inclusion of catheter-based methods as treatment option.Survival plot

Sarcoid Nodule or Lung Cancer? A High-Resolution Computed Tomography-Based Retrospective Study of Pulmonary Nodules in Patients with Sarcoidosis.

Background: The objective of this retrospective study was to compare the characteristics of sarcoid nodules and neoplastic nodules using high-resolution computed tomography (HRCT) in sarcoidosis patients. Methods: This is a single-center retrospective study. From 2010 to 2023, among 685 patients affected by pulmonary sarcoidosis, 23 patients developed pulmonary nodules of a suspicious malignant nature. The HRCT characteristics of biopsy-proven malignant (Group A) vs. inflammatory (Group B) nodules were analyzed and compared. Results: A significant difference was observed between the groups in terms of age (p = 0.012). With regard to HRCT features, statistical distinctions were observed in the appearance of the nodule, more frequently spiculated in the case of lung cancer (p < 0.01), in the diameter of the nodule (Group A: 23.5 mm; Group B: 12.18 mm, p < 0.02), in the median nodule density (Group A: 60.0 HU, Group B: -126.7 HU, p < 0.01), and in the number of pulmonary nodules, as a single parenchymal nodule was more frequently observed in the neoplastic patient group (p = 0.043). In Group A, the 18-PET-CT demonstrated hilar/mediastinal lymphadenopathy in 100% of cases; histology following surgery did not report any cases of malignant lymph node involvement. Conclusions: An accurate clinical evaluation and HRCT investigation are crucial for diagnosing lung cancer in patients with sarcoidosis in order to determine who requires surgical resection. The spiculated morphology of the nodule, greater size, the number of pulmonary nodules, and density using HRCT appear to correlate with the malignant nature of the lesion.

Incidence of head and neck cancer among Baquba Teaching Hospital Patients

Background: Squamous cells lining the tissues of the head and neck region, such as the nasal cavity, paranasal sinuses, oral cavity, lip, salivary glands, and hypopharynx, give growth to a group of malignancies together recognized as squamous cell carcinoma of the head and neck, which is the seventh utmost communal cancer diagnosis around the world. Objective: Determine the prevalence of head and neck cancer in Diyala province during 2022-2023 and their distribution according to age and gender of patients. In addition, this study aimed to identify the numbers of each type of head and neck cancer. Patients and Methods: A retrospective study achieved on the prevalence of head and neck cancer in the region accomplished in oncology center of Baquba teaching hospital in Diyala province, Iraq. Head and neck cancer patients recorded from 2022 to 2023. During this dated, a total of 172 patients were recorded. A search was accomplished on numerous databases, moreover, the information evaluated by age, gender and cancer type. Results: Regarding patients during 2022 (first group) which is contained of (94) patients with different head and neck cancer, 38(40.4%) were males and 56(59.6%) were females with statistically significant relationship. The patients during 2023 (second group) comprises of (78) patients with different head and neck cancer, 43(50.1%) were men and 35(44.9%) were women with statistically no significant correlation. Conclusion: Oral and pharyngeal cancer is more common in men than in women. The most common age group is 4th and 5th decade for head and neck cancer.