Non-malignant Groups Research Articles

Tumor Markers in Pleural Fluid: A Comprehensive Study on Diagnostic Accuracy.

Background/Objectives: Malignant pleural effusions (MPEs) pose a significant challenge in clinical practice and exert a considerable socio-economic burden on the healthcare system, affecting approximately 1 million individuals annually. These effusions are a leading cause of debilitating dyspnea and a diminished quality of life among cancer patients, with distant metastasis to the pleural layers occurring in about 20% of cases during treatment. Methods: A cross-sectional, observational case-control study was conducted on 151 Bulgarian patients with a hydrothorax. The control group included 72 patients with benign diseases, confirmed via biopsy, with 38 having inflammatory and 34 non-inflammatory pleural effusions. The other 79 patients had malignant pleural involvement. These groups are representative of the main types of pleural pathology. Results: The study found that all of the tumor markers, except for PIVKA-II (Protein induced by vitamin K absence-II), showed statistically significant differences between the malignant and non-malignant patient groups, with CAE (carcinoembryonic antigen) and CA19-9 showing the most notable differences. The Receiver Operating Characteristic (ROC) analysis revealed that CA72-4 had the best ability to distinguish between the two groups, while PIVKA was the weakest, with optimal cut-off values for all of the relevant tumor markers being derived using the Youden index. Conclusions: In conclusion, our study highlights the transformative potential of pleural fluid tumor markers as precise and minimally invasive resources for distinguishing malignant from non-malignant pleural effusions. These findings pave the way for improved diagnostic accuracy and personalized clinical management, addressing a critical gap in the care of patients with pleural pathologies.

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.

Peripheral immune signatures associated with the risk of hepatocarcinogenesis in cirrhotic Egyptian HCV patients before and after treatment with direct-acting antivirals

BackgroundAlthough direct-acting antivirals (DAAs) have revolutionized the management of chronic HCV, the debatable association with hepatocellular carcinoma (HCC) occurrence/recurrence has raised major concerns about their long-term use, especially in cirrhotic cases. The role of epithelial tight junction proteins (TJPs) in hepatocarcinogenesis has been highlighted; however, the association of their expression in peripheral blood mononuclear cells (PBMCs) with HCC has rarely been reported. This study aimed to explore the role of peripheral claudin (Cldn)1 in liver pathogenesis and its crosstalk with soluble immune mediators in HCC prognosis.MethodsThe study population included six independent subgroups: healthy controls, cirrhotic/non-cirrhotic treatment-naïve HCV patients, DAA-SVR patients, and anticancer treatment-naïve de novo HCC patients. The laboratory tests included serum levels of alpha-fetoprotein (AFP), albumin, liver transaminases, total bilirubin, and CBC profiling. The serum levels of soluble cluster of differentiation (sCD)163, IL-10, and IL-12 were estimated by corresponding ELISA kits, whereas the levels of Cldn1 and transforming growth factor (TGF)-β in PBMCs were quantified using quantitative PCR (qPCR).ResultsSerum sCD163, IL-10, and IL-12 levels were significantly higher in the HCC patient group than in the control and non-malignant patient groups (P < 0.0001). No significant difference was detected in the serum levels of the three markers between cirrhotic and non-cirrhotic patients of chronic HCV, whereas their levels were significantly different between cirrhotic and non-cirrhotic SVRs (P < 0.0001). Similarly, the transcriptional levels of peripheral Cldn1 and TGF-β were significantly higher in patients with HCC and non-malignant cirrhosis than in patients without cirrhosis (P = 0.0185–<0.0001 and 0.0089–<0.0001, respectively). Logistic regression analysis revealed a significant association between all the abovementioned markers and HCC (P = 0.0303 to < 0.0001), which was further confirmed by the results of receiver operating characteristic (ROC) analysis, which revealed an area under the curve (AUC) value ranging from 0.883 to 0.996. The calculated cutoff values demonstrated remarkable prognostic capacity, with ranges of 88–99.41% and 82.14–97.92% and positive/negative predictive values ranging from 84.62 to 98.3% and 92–98%, respectively.ConclusionSerum sCD163, IL-10, IL-12 and peripheral Cldn1 and TGF-β expression levels represent novel non-invasive HCC biomarkers that maintain their predictive power under different pathological conditions and circumvent the drawbacks of conventional prognostic markers in patients with mild cirrhosis and/or normal AFP, albumin, and/or platelet counts.

A multicenter retrospective study on clinical features and pathogenic composition of septic shock in children

Objective: To investigate the clinical features, pathogen composition, and prognosis of septic shock in pediatric intensive care units (PICU) in China. Methods: A multicenter retrospective cohort study. A retrospective analysis was conducted on the clinical data of children with septic shock from 10 hospitals in China between January 2018 and December 2021. The clinical features, pathogen composition, and outcomes were collected. Patients were categorized into malignant tumor and non-malignant tumor groups, as well as survival and mortality groups. T test, Mann Whitney U test or Chi square test were used respectively for comparing clinical characteristics and prognosis between 2 groups. Multiple Logistic regression was used to identify risk factors for mortality. Results: A total of 1 247 children with septic shock were included, with 748 males (59.9%) and the age of 3.1 (0.9, 8.8) years. The in-patient mortality rate was 23.2% (289 cases). The overall pathogen positive rate was 68.2% (851 cases), with 1 229 pathogens identified. Bacterial accounted for 61.4% (754 strains) and virus for 24.8% (305 strains). Among all bacterium, Gram negative bacteria constituted 64.2% (484 strains), with Pseudomonas aeruginosa and Enterobacter being the most common; Gram positive bacteria comprised 35.8% (270 strains), primarily Streptococcus and Staphylococcus species. Influenza virus (86 strains (28.2%)), Epstein-Barr virus (53 strains (17.4%)), and respiratory syncytial virus (46 strains (17.1%)) were the top three viruses. Children with malignant tumors were older and had higher pediatric risk of mortality (PRISM) Ⅲ score, paediatric sequential organ failure assessment (pSOFA) score (7.9 (4.3, 11.8) vs. 2.3 (0.8, 7.5) years old, 22 (16, 26) vs. 16 (10, 24) points, 10 (5, 14) vs. 8 (4, 12) points, Z=11.32, 0.87, 4.00, all P<0.05), and higher pathogen positive rate, and in-hospital mortality (77.7% (240/309) vs. 65.1% (611/938), 29.7% (92/309) vs. 21.0% (197/938), χ2=16.84, 10.04, both P<0.05) compared to the non-tumor group. In the death group, the score of PRISM Ⅲ, pSOFA (16 (22, 29) vs. 14 (10, 20) points, 8 (12, 15) vs. 6 (3, 9) points, Z=4.92, 11.88, both P<0.05) were all higher, and presence of neoplastic disease, positive rate of pathogen and proportion of invasive mechanical ventilation in death group were also all higher than those in survival group (29.7% (87/289) vs. 23.2% (222/958), 77.8% (225/289) vs. 65.4% (626/958), 73.7% (213/289) vs. 50.6% (485/958), χ2=5.72, 16.03, 49.98, all P<0.05). Multiple Logistic regression showed that PRISM Ⅲ, pSOFA, and malignant tumor were the independent risk factors for mortality (OR=1.04, 1.09, 0.67, 95%CI 1.01-1.05, 1.04-1.12, 0.47-0.94, all P<0.05). Conclusions: Bacterial infection are predominant in pediatric septic shock, but viral infection are also significant. Children with malignancies are more severe and resource consumptive. The overall mortality rate for pediatric septic shock remains high, and mortality are associated with malignant tumor, PRISM Ⅲ and pSOFA scores.

6913 Clinical Prognosis in Patients with Thyroid Nodules Expressing PPAR-Gamma Gene Fusion on Thyroid FNA Cytology

Abstract Disclosure: R. Hammoudeh: None. E. Morariu: None. A. Wald: Other; Self; Technical consultant to Sonic Healthcare USA.. W.R. Doerfler: None. Y. Linwah: None. M. Nikiforova: Owner/Co-Owner; Self; Owner of intellectual property related to ThyroSeq, receive royalties through the University of Pittsburgh; consultants for Sonic Healthcare USA. Y.E. Nikiforov: Owner/Co-Owner; Self; Owner of intellectual property related to ThyroSeq, receive royalties through the University of Pittsburgh; consultants for Sonic Healthcare USA. Background: PPARG rearrangements, typically PAX8-PPARG, are common genetic alterations in follicular thyroid carcinoma and follicular variant of papillary thyroid carcinoma (FVPTC). Most tumors appear to be indolent, however distant metastasis has been reported. The aim of this study was to determine the prevalence and type of malignancy in a series of thyroid nodules positive for PAX8 rearrangement in thyroid fine-needle aspiration (FNA) samples. We also aimed to evaluate the impact on patient management, prognosis and outcomes. Methods: Thyroid nodules positive for PAX8 fusion on ThyroSeq v2 and v3 genomic classifier testing of FNA samples from May 2008 to February 2022 were identified. Clinical data was obtained by retrospective chart review. Results: Overall, 44 nodules positive for PAX8/PPARG fusion were identified. None of these nodules expressed additional genetic mutations on molecular testing. Surgical pathology was available for 40 patients, which identified 35 (87.5%) malignant, 3 NIFTP (7.5%), and 2 benign (5%) lesions. In the malignant group, FNA cytology revealed 1 (2.8%) benign, 13 (37.1%) AUS/FLUS, 12 (34.2%) suspicious for SFN/FN, 5 (14.3%) suspicious for PTC and 4 were not classified. In the non-malignant group, FNA cytology revealed 2 (40%) benign, 2 (40%) AUS/FLUS, 1 (20%) SFN/FN. With regards to surgical intervention, 30 (75%) patients had total thyroidectomy and 10 (25%) underwent lobectomy, of which 8 were followed by completion thyroidectomy. Among the malignant and non-malignant groups, there was no difference in sex (82.8% vs 100% female, p=1), age (43.6 vs 50.2 years, p=0.2), or tumor size on surgical pathology (3.26 vs 4 cm, p=0.23). In the malignant group, histology showed 30 (85.7%) FVPTC, 2 (5.7%) conventional PTC, 2 (5.7%) follicular carcinoma and 1 (2.9%) solid variant PTC. Of the FVPTC group, 9 had oncocytic cell features, 3 focal solid patterns, and 1 showed focal solid growth and progression to poorly differentiated thyroid carcinoma. Only 1 showed lymphatic invasion, 10 showed angioinvasion. Following the ATA thyroid cancer risk stratification, 23 (65.7%%) had low risk, 9 (25.7%) intermediate risk and 3 (8.6%) high risk. 18 patients in the malignant group underwent RAI ablation. Average follow up for the malignant nodules was 49.7 months (0-170). 1 had suspected recurrence on thyroid ultrasound after a year. No evidence of distant metastasis was documented. Conclusions: The majority of thyroid nodules with PAX8/PPARG rearrangement found on FNA were cancers, predominantly follicular variant PTC, and some were benign or NIFTP. The majority were low risk, but intermediate and high-risk cancers with more aggressive histology, angioinvasion, and poorly differentiated cancer were also identified. While only one recurrence was identified on short follow-up, longer follow-up duration is required for better understanding the behavior of these tumors. Presentation: 6/3/2024

Role of Combining Grayscale Findings With Superb Microvascular Imaging and Shear Wave Elastography in Standardization and Management of NON-MASS Breast Lesions.

The non-mass breast lesions on ultrasound (US) are a group of challenging pathology. We aimed to standardize these grayscale findings and investigate the effectiveness of superb microvascular imaging (SMI) and shear wave elastography (SWE). A total of 195 lesions were evaluated by B-mode US, SWE, and SMI in the same session. A "NON-MASS model" was built on grayscale US to group the lesions only as areas and those with associated features: microcalcifications, architectural distortion, ductal changes, and microcysts. The mean stiffness parameters Emean, Eratio, and mean vascular index (VI) were recorded following consecutive measurements. Besides, the microvascularity was graded based on Adler's classification (grades 0 to 3). Lesions were divided into 3 groups: benign, category B3, and malignant. One hundred twelve (57.4%) lesions were benign, 23 (11.8%) were B3, and 60 were (30.8%) in the malignant category. Thirty-eight (19.5%) lesions were observed only as an area, whereas associated features were present in 157 lesions (80.5%). Distortion was the only associated feature predicting malignancy among the grayscale findings (P < 0.001). There was a significant difference between malignant and nonmalignant (benign and B3) groups in terms of Adler's grade, Emean, Eratio, and VI values (P < 0.001). Sensitivity, specificity, and accuracy increased when advanced imaging parameters were added to grayscale findings (P < 0.001). In the presence of microcalcifications, architectural distortion, high elasticity, and hypervascularity in the "NON-MASS" imaging model, the suspicion of malignancy increases. The non-mass findings and advanced imaging techniques have the potential to find greater coverage in the following versions of BI-RADS atlas.

The Diagnostic Value of Endobronchial Ultrasound-Guided Fine Needle Aspiration (EBUS-FNA) in Diagnosing FDG-PET-Avid Lymph Nodes in Extrapulmonary Malignancies.

Background and objective The accurate diagnosis of extrapulmonary malignancies with mediastinal lymphadenopathy is crucial for effective patient management. Endobronchial ultrasound-guided fine-needle aspiration(EBUS-FNA)has emerged as a valuable tool in assessingfluorodeoxyglucose (FDG)-positron emission tomography(PET)-avid lymph nodes (LNs).In this study, we aimed to evaluate the diagnostic value of EBUS-FNA in patients with mediastinal lymphadenopathy in extrapulmonary malignancies and compare its efficacy with PET-CT. Methodology Thisretrospective, cross-sectional study was conducted at Shaukat Khanum Memorial Cancer Hospital and Research Center, Lahore, from February 2018 to February 2023. It included patients with extrapulmonary malignancies with mediastinal lymphadenopathy displaying abnormal PET-CT uptake, with LN diameters ≥5 mm, excluding lung cancer cases. Data on demographics, malignancy type, LN involvement, PET-CT findings, and EBUS-FNA histopathology were collected. EBUS-FNA procedures involved a 22-gauge needle, and samples were analyzed cytologically and histologically. SPSS Statistics version 20 (IBM Corp., Armonk, NY) was used to perform the statistical analysis. Results The study analyzed a total of 216 patients. Males comprised 56.3% of the cohort, and females 43.7%. The most common malignancy was lymphoma (33.0%), followed by breast cancer (12.6%). EBUS-FNA exhibited a sensitivity of 90.9% compared to PET-CT's sensitivity of 72.7%. Lymph node morphology on EBUS showed low echogenicity and irregular borders in malignant cases. Subcarinaland right hilar were the most frequently sampled lymph nodes. The study found significant differences in lymph node characteristics between non-malignant and malignant groups, with EBUS-FNA effectively identifying malignancies. Conclusions EBUS-FNA demonstrates high sensitivity and diagnostic utility in identifying malignant lymph nodes in patients with extrapulmonary malignancies. Its effectiveness in detecting true positive cases highlights its importance as a complementary diagnostic tool to PET-CT in oncological diagnostics.

When is it necessary to perform biopsy in asymptomatic postmenopausal women with incidental finding of thickened endometrium?

ObjectiveTo determine the cutoff value for endometrial thickness (ET) that prompts a biopsy in asymptomatic postmenopausal women with an incidental finding of thickened endometrium, and to develop a risk prediction model. MethodsThis is a retrospective cohort analysis of the clinical records of the Hysteroscopic Center of Fu Xing Hospital, Capital Medical University, Beijing, China. We collected asymptomatic postmenopausal women who presented with an ET of ≥4 mm (double-layer) as an incidental finding. We stratified the participants into non-malignant and malignant groups based on pathology results and assessed differences between the two groups. A receiver operating characteristic curve (ROC) was used to identify the cutoff value of ET for predicting endometrial malignancy. Logistic regression models were also constructed to predict the risk of malignancy. ResultsA total of 581 consecutive eligible cases were included. The optimal cutoff value for ET was 8 mm, with a maximum area under the curve (AUC) of 0.755 (95 % CI: 0.645–0.865). In addition to ET, the regression model incorporated diabetes, blood flow signal, BMI, and hypertension to predict the risk of malignancy. A ROC curve constructed for the model yielded an AUC of 0.834 (95 % CI: 0.744–0.924). ConclusionIt is reasonable to offer hysteroscopy and visually-directed endometrial biopsy for asymptomatic postmenopausal women when ET is 8 mm or above. For those with an ET between 4 and 8 mm, further decision to perform biopsy should be determined on an individual basis, considering risk factors and blood flow signals of the endometrium.

A Retrospective Cohort of Tumor-Induced Osteomalacia and Case Series of Malignant Disease.

Tumor-induced osteomalacia (TIO) is a rare condition with evidence mostly derived from case reports and case series. We aimed to describe the clinical characteristics of a large cohort of patients diagnosed with TIO, with a focus on patients with nonlocalizing and malignant TIO. This is a retrospective cohort of patients with TIO in an academic medical center, diagnosed between January 1998 and May 2023. We describe their demographics, biochemistries, tumor features, localization, treatment, and complications. Of 68 patients diagnosed with TIO, 49 (72%) were localizing and 5 (7.4%) were malignant. Of 50 patients who attempted localizing procedures, 29 (58%) achieved cure. Twenty (40%) had persistent disease due to the wrong tumor targeted, or refractory or recurrent tumors, despite up to 6 procedural attempts. There was no difference in demographics, phosphorus, or baseline fibroblast growth factor-23 (FGF23) levels between localizing vs nonlocalizing groups, and malignant vs nonmalignant groups. The lower extremity was the commonest site of localization (37%), with 47% in bone and 53% in soft tissue. Sixty percent of malignant cases were located in the trunk. Tumor size correlated with peak FGF23 (R = 0.566, P < .001) but was not associated with malignancy risk (P = .479). A cut-off FGF23 of >20 times upper limit of normal in the presence of normal renal function (P = .025) and recurrence after initial cure (P = .013) were factors significantly associated with malignancy. The nonlocalizing group had lower survival than the localizing group (P = .0097). TIO is a condition with significant morbidity. Very high FGF23 levels and disease recurrence are associated with malignant disease. Reasons behind the observation of higher mortality in nonlocalizing TIO should be further explored.

Pericardial Fluid Analysis in Diagnosis and Prognosis of Patients Who Underwent Pericardiocentesis

In this study, we aimed to examine the diagnostic yield of pericardial fluid biochemistry and cytology and their prognostic significance in patients with percutaneously drained pericardial effusions, with and without malignancy. This is a single-center, retrospective study of patients who underwent pericardiocentesis between 2010 and 2020. Data were extracted from electronic patient records, including procedural information, underlying diagnosis, and laboratory results. Patients were grouped into those with and without underlying malignancy. A Cox proportional hazards model was used to analyze the association of variables with mortality. The study included 179 patients; 50% had an underlying malignancy. There were no significant differences in pericardial fluid protein and lactate dehydrogenase between the 2 groups. Diagnostic yield from pericardial fluid analysis was greater in the malignant group (32% vs 11%, p = 0.002); 72% of newly diagnosed malignancies had positive fluid cytology. The 1-year survival was 86% and 33% in nonmalignant and malignant groups, respectively (p <0.001). Of 17 patients who died within the nonmalignant group, idiopathic effusions were the largest group (n = 6). In malignancy, lower pericardial fluid protein and higher serum C-reactive protein were associated with increased risk of mortality. In conclusion, pericardial fluid biochemistry has limited value in determining the etiology of pericardial effusions; fluid cytology is the most important diagnostic test. Mortality in malignant pericardial effusions may be associated with lower pericardial fluid protein levels and a higher serum C-reactive protein. Nonmalignant pericardial effusions do not have a benign prognosis and close follow-up is required. In this study, we aimed to examine the diagnostic yield of pericardial fluid biochemistry and cytology and their prognostic significance in patients with percutaneously drained pericardial effusions, with and without malignancy. This is a single-center, retrospective study of patients who underwent pericardiocentesis between 2010 and 2020. Data were extracted from electronic patient records, including procedural information, underlying diagnosis, and laboratory results. Patients were grouped into those with and without underlying malignancy. A Cox proportional hazards model was used to analyze the association of variables with mortality. The study included 179 patients; 50% had an underlying malignancy. There were no significant differences in pericardial fluid protein and lactate dehydrogenase between the 2 groups. Diagnostic yield from pericardial fluid analysis was greater in the malignant group (32% vs 11%, p = 0.002); 72% of newly diagnosed malignancies had positive fluid cytology. The 1-year survival was 86% and 33% in nonmalignant and malignant groups, respectively (p <0.001). Of 17 patients who died within the nonmalignant group, idiopathic effusions were the largest group (n = 6). In malignancy, lower pericardial fluid protein and higher serum C-reactive protein were associated with increased risk of mortality. In conclusion, pericardial fluid biochemistry has limited value in determining the etiology of pericardial effusions; fluid cytology is the most important diagnostic test. Mortality in malignant pericardial effusions may be associated with lower pericardial fluid protein levels and a higher serum C-reactive protein. Nonmalignant pericardial effusions do not have a benign prognosis and close follow-up is required.

A Single Tertiary Center 14-year Experience With Mesenteric Panniculitis in Turkey: A Retrospective Study of 716 Patients.

Mesenteric panniculitis is a chronic inflammatory process seen in mesenteric tissue. The purpose of this study was to assess the prevalence, clinical, laboratory, and radiological findings, and malignancy in patients diagnosed with mesenteric panniculitis using computed tomography. A total of 716 patients with mesenteric panniculitis were retrospectively evaluated by screening all computed tomography scans performed between January 2005 and December 2018. Among 65 278 patients undergoing CT, 716 were diagnosed with mesenteric panniculitis. The prevalence of mesenteric panniculitis was 1.1%. The mean age was 56 ± 14 (20-91) years. The malignant and nonmalignant groups comprised 354 (49.4%) and 362 (50.6%) patients, respectively. The mean age of the malignant group was significantly higher than the nonmalignant group (P < .001). The most common malignancy was breast cancer (12.2%). A history of abdominal surgery was present in 179 (25%) patients with mesenteric panniculitis and it is higher in the malignant group than the nonmalignant group (128 [36.1%], 51 [14%], respectively, P < .001). Mean hemoglobin level and leukocyte count were lower in the malignant group than in the nonmalignant group (P < .001, P < .001, respectively). The mean erythrocyte sedimentation rate was higher in the malignant group than in the nonmalignant group (P = .030). Radiological criterion 2 was less common and radiological criterion 5 was more common in the malignant group than the nonmalignant group (91.0%, 96.4%, P = .004; 35.9%, 27.1%, respectively, P = .011). It is recommended to conduct research for malignancy in patients with mesenteric panniculitis, especially in the presence of clinical, laboratory, and radiological findings with high-risk features.

Human Papillomavirus (HPV) Prevalence and E6 Protein Expression in Gastric Cancer Tissue Samples Compared with Non-malignant and Control Groups in East Azerbaijan Province, Iran, 2021

<i>Human Papillomavirus</i> (<i>HPV</i>) Prevalence and E6 Protein Expression in Gastric Cancer Tissue Samples Compared with Non-malignant and Control Groups in East Azerbaijan Province, Iran, 2021

Percutaneous balloon pericardiotomy: efficacy in a series of malignant and nonmalignant cases

Objective: In the case of malignant pericardial effusion and cardiac tamponade, balloon pericardiotomy is an established minimally invasive option to the surgical creation of a subxiphoid pericardial window. Percutaneous balloon pericardiotomy effectively drains recurrent pericardial fluid by creating a pleuro (-abdominal-) pericardial communication. Design. A series of 26 patients with underlying malignant (n = 12) and nonmalignant (n = 14) diseases underwent percutaneous balloon pericardiotomy between 2008 and 2021. All interventions were done through a subxiphoid access under local anesthesia. Results. The mean survival in the malignant and nonmalignant groups was 1.2 versus 48.0 months, respectively (p < .001). There were neither severe periinterventional complications nor in-hospital deaths. In two patients with nonmalignant disease the surgical creation of a pericardial window was necessary during follow-up. The originally described procedure was modified by the removal of all catheters at the end of the intervention. The procedure was safe. It prevented immobility and facilitated an early discharge from the hospital. Conclusion. Our experiences show that percutaneous balloon pericardiotomy is a minimally invasive approach to successfully provide palliation in the group of patients with underlying malignant disease. On the other hand, we have shown that this technique is safe and feasible in the treatment of pericardial effusion based on nonmalignant disease. We think thereby that pericardial balloon pericardiotomy can be considered as a less invasive alternative to surgery in both groups of patients.

Complex metabolic interactions between ovary, plasma, urine, and hair in ovarian cancer.

Ovarian cancer (OC) is the third most common malignant tumor of women accompanied by alteration of systemic metabolism, yet the underlying interactions between the local OC tissue and other system biofluids remain unclear. In this study, we recruited 17 OC patients, 16 benign ovarian tumor (BOT) patients, and 14 control patients to collect biological samples including ovary plasma, urine, and hair from the same patient. The metabolic features of samples were characterized using a global and targeted metabolic profiling strategy based on Gas chromatography-mass spectrometry (GC-MS). Principal component analysis (PCA) revealed that the metabolites display obvious differences in ovary tissue, plasma, and urine between OC and non-malignant groups but not in hair samples. The metabolic alterations in OC tissue included elevated glycolysis (lactic acid) and TCA cycle intermediates (malic acid, fumaric acid) were related to energy metabolism. Furthermore, the increased levels of glutathione and polyunsaturated fatty acids (linoleic acid) together with decreased levels of saturated fatty acid (palmitic acid) were observed, which might be associated with the anti-oxidative stress capability of cancer. Furthermore, how metabolite profile changes across differential biospecimens were compared in OC patients. Plasma and urine showed a lower concentration of amino acids (alanine, aspartic acid, glutamic acid, proline, leucine, and cysteine) than the malignant ovary. Plasma exhibited the highest concentrations of fatty acids (stearic acid, EPA, and arachidonic acid), while TCA cycle intermediates (succinic acid, citric acid, and malic acid) were most concentrated in the urine. In addition, five plasma metabolites and three urine metabolites showed the best specificity and sensitivity in differentiating the OC group from the control or BOT groups (AUC > 0.90) using machine learning modeling. Overall, this study provided further insight into different specimen metabolic characteristics between OC and non-malignant disease and identified the metabolic fluctuation across ovary and biofluids.

A retrospective study of treosulfan versus busulfan-based conditioning in pediatric patients.

To compare the outcomes of treosulfan-based vs busulfan-based conditioning regimens in allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric patients. Retrospective study of all consecutive patients (2012-2019) treated with allogenic HSCT and treosulfan- or busulfan-based conditioning regimens at a single center. A total of 101 HSCT were included: 66 HSCT with busulfan and 35 with treosulfan. In malignant diseases (n=62), busulfan-based conditioning was more commonly employed than treosulfan: 82.3% vs 17.7%. However, the use of treosulfan for malignant diseases increased over time: 6.5% of HSCT in 2012-2015 vs 29% of HSCT in 2015-2019 (p=.02). The cohort of treosulfan had more children under 1-year of age than the busulfan cohort (31 vs 13%; p=.033). The percentage of patients who received serotherapy was 73 and 89% in the nonmalignant and malignant groups, respectively. The engraftment, time to neutrophil, and platelet engraftment were not significantly different between the busulfan and the treosulfan cohorts. Rate of grade II-IV acute GvHD was significantly higher in the busulfan cohort than the treosulfan cohort (39% vs 15%; p=.016). No differences were observed in endothelial damage complications, chronic GvHD, relapse, overall survival, and transplant-related mortality. Busulfan-based conditioning regimens are used more frequently for children undergoing allogenic HSCT, but treosulfan-based conditioning is gaining acceptance. Treosulfan-based conditioning is associated with lower rates of acute GvHD, and no significant differences on overall survival were observed compared with busulfan.

The Role of Ca 19-9, Ca 72-4, Cea and Cholesterol Levels in Predicting Malignancy in Gallbladder Polyps.

To determine the association of malignancy potential of gallbladder polyps with tumor markers and cholesterol levels, and at which value the presence of malignancy should be suspected. Observational study. University of Health Sciences, Adana City training and research Hospital from December 2017 to November 2020. Ninety patients diagnosed with gallbladder polyp by abdominal ultrasonography, were included in the study. Patients were divided into subgroups of true pseudopolyp, cholesterol-non-cholesterolpolyp, malignant-non-malignant polyp. The groups were compared in terms of age, gender, polyp size, number of polyps, preoperative total cholesterol, HDL (high-density lipoprotein), LDL (low-density lipoprotein), triglyceride, Ca 19-9 (carbohydrate antigen 19-9), Ca 72-4 (carbohydrate antigen 72-4), Cea (carcinoembryonic antigen) levels. In the true polyp group, polyp size, Ca 19-9, Ca 72-4 and Cea median values were significantly higher (p=0.001, p=0.029, p=0.003, and p=0.007, respectively); whereas, triglyceride levels were significantly lower compared to the pseudopolyp group (p=0.002). Polyp size was significantly lower in cholesterol polyp group compared to non-cholesterol polyp group (p= 0.032), and LDL and triglyceride medians were significantly higher (p=0.031, and p<0.001) in cholesterol group. Among the true polyps, polyp size, Ca 19-9, Ca 72-4 and Cea levels were significantly higher in adenocarcinoma group than non-malignant polyp groups (p<0.05). Cut-off values were determined as >11 mm AUC: 0.906 for size, >24.1 U/mL. AUC: 1.00 for Ca 19-9, >9.6 U/mL AUC: 1.00 for Ca 72-4, and >40 ng/mL AUC: 0.984 for CEA, respectively. Polyps larger than 11mm with high levels of CEA, Ca 72-4, Ca 19-9, evaluated together, may act as a guide for the clinician in predicting malignancy. The availability of economical and accessible parameters may allow a new algorithm to be developed in the treatment and follow-up approach of gallbladder polyps. Key Words: Gallbladder polpys, Ca 19-9 antigen, Ca 72-4 antigen, Tumor marker, Gallbladder cancer.

MiR-34a-5p suppresses colorectal cancer cell proliferation through silencing Microtubule Actin Crosslinking Factor 1 (MACF1) gene

BackgroundColorectal cancer (CRC) is the third most frequent cancer in both males and females. CRC results from multiple causes including genetic, epigenetic, and environmental insults. One of the newly identified oncogenes is the Microtubule Actin Crosslinking Factor 1 (MACF1) gene. MACF1 plays a critical role in colon cancer cell proliferation and progression through Wnt /β catenin pathway. Accordingly, we hypothesized that targeting MACF1 would affect CRC progression. Methodsbioinformatics analysis revealed that MACF1 is a target of miR-34a-5p. miR-34a-5p and MACF1 relative expression were measured in 40 colorectal cancers, 40 nonmalignant colon tissue samples using RT- qPCR. "CaCo2" cells line was transfected with miR-34a-5p mimic to assess the effect of MACF1 gene silencing on colorectal cell growth in vitro. ResultsmiR-34a-5p relative expression was significantly lowered in the colorectal cancer group than its expression in nonmalignant groups (P < 0.01). While MACF1 expression was significantly overexpressed in the colorectal cancer group as compared to the nonmalignant groups (P < 0.01). CaCo2 cells' proliferation significantly inhibited after transfection with miR-34a-5p mimic. This inhibited growth was associated with a significant decrease in MACF1 expression. ConclusionThese findings suggest that miR-34a-5p may inhibit colorectal cancer cell proliferation through downregulation of MACF1a member of Wnt/β catenin signaling. This study highlights the novel role of MACF1 as an indicative biomarker and therapeutic goal in colorectal cancer.

The diagnostic performance of conventional ultrasound and strain elastography in malignant soft tissue tumors.

To investigate the diagnostic value of conventional ultrasound (US) and strain elastography (SE) in malignant soft tissue tumors. A total of 83 soft tissue masses were included prospectively. US and SE imaging were performed at the same time. Two observers assessed the B mode, color Doppler, elastic scores (ES), strain ratio (SR), and SE size to B mode size (EI/B) ratio and compared the consistency of the data between the observers. According to the pathological diagnosis of resection, the cases were divided into malignant and nonmalignant groups. The diagnostic value of conventional US and SE in the prediction of malignant soft tissue tumors was assessed. The pathology results divided cases into 36 malignant lesions and 47 nonmalignant lesions. There was no statistically significant difference in gender, location, maximum diameter, echo, tail sign, cystic component, Doppler scores, or SR between the two groups (p > 0.05). However, significant differences between the two groups were found in age, depth, heterogeneity, edge, ES, and EI/B (p < 0.05). The biggest area under the receiver operating characteristics curve (0.934) was the combination model of age, heterogeneity, edge, ES, and EI/B, and the sensitivity and specificity were 0.861 and 0.957, respectively. Conventional US and SE are significant for the diagnosis of malignant soft tissue tumors, and SE can be used as a complementary technique to the characterization of STTs using conventional US.

Focal parenchymal atrophy of pancreas: An important sign of underlying high-grade pancreatic intraepithelial neoplasia without invasive carcinoma, i.e., carcinoma in situ

ObjectivesDiagnosing high-grade intraepithelial neoplasia without invasion, traditionally referred to as carcinoma in situ (CIS), is essential for improving prognosis. We examined the imaging findings of patients with and without CIS to identify significant aspects for the diagnosis of CIS. MethodsForty-six patients strongly suspected of early pancreatic cancer without nodule on imaging (CIS group, n = 27; non-malignant group, n = 19) were retrospectively evaluated according to ten factors of computed tomography/magnetic resonance imaging (CT/MRI), endoscopic ultrasonography (EUS), and endoscopic retrograde cholangiopancreatography (ERCP) using hierarchical cluster and univariate analyses. ResultsTwo clusters were formed by hierarchical cluster analysis. One cluster consisted of 83.3% CIS cases with similar image findings such as focal pancreatic parenchymal atrophy (FPPA) on CT/MRI, main pancreatic duct (MPD) stricture surrounded by hypoechoic areas on EUS, and MPD stricture with upstream MPD dilation on ERCP. On univariate analysis, the CIS and non-malignant groups had FPPA on CT/MRI in 15 (55.6%) and 3 (15.8%) cases (p = 0.013), and MPD stricture surrounded by hypoechoic areas on EUS in 20 (74.1%) and 4 (21.1%) cases (p = 0.001), respectively. MPD stricture surrounded by hypoechoic areas was observed in 80% (12/15) of CIS cases with FPPA on CT/MRI and correlated with FPPA. Moreover, FPPA and MPD stricture surrounded by hypoechoic areas had histopathologically observed fibrosis or fat replacement due to pancreatic parenchymal atrophy. ConclusionsFPPA and MPD stricture surrounded by hypoechoic areas are significant findings for the diagnosis of CIS.

The efficacy of the regimens of “graft versus host” disease prophylaxis after hematopoietic stem cell transplantation from unrelated donors in children: single center experience

Graft versus host” disease (GvHD) is one of the most frequent and severe complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The optimal model of GvHD prophylaxis in allo-HSCT from alternative donors in children currently remains actual question. Materials and methods. The study was approved by the Independent Ethics Committee and the Scientific Council of the N.N. Blokhin National Medical Research Center of Oncology, Ministry of Healthcare of Russian Federation. Two hundred fifty six allo-HSCT were made during the period 2003–2019 from matched unrelated donors (MUD). Age median was 7.1 years old. The source of hematopoietic stem cells (HSCs) bone marrow – 76% (n = 194), peripheral blood stem cells – 24% (n = 62). GvHD prophylaxis included: tacrolimus (Tacro), cyclosporin A (CsA), methotrexate (Mtx), mycophenolate mofetil (MMF), in following combinations Tacro/Mtx (n = 98), Tacro/MMF (n = 102), tacro/Mtx + MMF (n = 3), CsA/Mtx (n = 24), CsA/Mtx + MMF (n = 12), CsA + MMF (n = 14). Median follow-up 8.9 years. GvHD prophylaxis regimen did not affect significantly the toxicity of therapy (toxicity: severe mucositis grade III–IV, nephrotoxicity, hepatotoxicity) (p = 0.4; p = 0.24; p = 0.62 respectively). In our study the rate of the overall survival (ОS) has significant differences in depending of the source of prevention GvHD. The using a combination of tacrolimus and cyclosporine with low doses of methotrexate had a positive effect on OS (p = 0.035) in patients of common non-malignant and malignant groups, as well as on the level of 2-year relapse-free survival in the group of children with malignant disorders (p = 0.671). In the general group the OS the worst results were achieved when MMF was included in the prophylaxis model. In this experience of treating of a large cohort of patients the choice of calcineurin inhibitors and methotrexate as the agent GvHD prophylaxis showed the efficacy and safety for non-manipulated MUD for both malignant and non-malignant diseases in children.