Malignant Origin Research Articles

Case series of small bowel obstruction

Introduction: Small Bowel Obstruction remains a significant cause of morbidity and mortality, accounting for 12%-16% of hospital admissions for acute abdominal pain in the United States. Imaging typically provides insights into the degree of obstruction, its cause, and whether the case is severe or complicated. This study aimed to examine cases of small bowel obstruction, encompassing patient complaints, radiological findings, and prognosis. Case description: The first case involves a 51-year-old male patient presenting with complaints of abdominal bloating for the past week. Physical examination and additional diagnostic tests indicated the patient was experiencing either partial ileus obstruction or total ileus obstruction, with total bowel obstruction suspected to be of malignant origin. The patient was treated in the ICU for two days, and then transferred to a general ward for five days before passing away. The second case involves a 57-year-old female patient presenting with complaints of epigastric pain for the past three days. Physical examination and additional diagnostic tests revealed either partial ileus obstruction or total ileus obstruction, with total bowel obstruction suspected to be of malignant origin. The patient was treated in the ICU for three days, followed by six days in a general ward. The patient showed significant improvement and was discharged with a recommendation for outpatient follow-up care at the polyclinic. Conclusion: Both cases presented here demonstrated the presence of obstruction through clinical history, physical examination, laboratory findings, and radiology. Initial management was conservative, followed by laparotomy as the surgical approach.

Mammographic Vascular Microcalcifications as a Surrogate Parameter for Coronary Heart Disease: Correlation to Cardiac Computer Tomography and Proposal of a Classification Score.

This study develops a BI-RADS-like scoring system for vascular microcalcifications in mammographies, correlating breast arterial calcification (BAC) in a mammography with coronary artery calcification (CAC), and specifying differences between microcalcifications caused by BAC and microcalcifications potentially associated with malignant disease. This retrospective single-center cohort study evaluated 124 consecutive female patients (with a median age of 57 years). The presence of CAC was evaluated based on the Agatston score obtained from non-enhanced coronary computed tomography, and the calcifications detected in the mammography were graded on a four-point Likert scale, with the following criteria: (1) no visible or sporadically scattered microcalcifications, (2) suspicious microcalcification not distinguishable from breast arterial calcification, (3) minor breast artery calcifications, and (4) major breast artery calcifications. Inter-rater agreement was assessed in three readers using the Fleiss' kappa, and the correlation between CAC and BAC was evaluated using the Spearman's rank-order and by the calculation of sensitivity/specificity. The reliability of the visual classification of BAC was high, with an overall Fleiss' kappa for inter-rater agreement of 0.76 (ranging between 0.62 and 0.89 depending on the score). In 15.1% of patients, a BAC score of two was assigned indicating calcifications indistinguishable regarding vascular or malignant origin. In 17.7% of patients, minor or major breast artery calcifications were found (BAC 3-4). BAC was more prevalent among the patients with CAC (p < 0.001), and the severity of CAC increased with the BAC score; in the group with a BAC score of one, 15% of patients exhibited mild and severe CAC, in those with a BAC of two, this was 31%, in those with BAC of three, this was 38%, and in those with a BAC of four, this was 44%. The sensitivity for detecting CAC, based on the mammographic BAC score, was 30.3% at a specificity of 96.7%. The standardized visual grading of BAC in mammographies on a four-point scale is feasible with substantial interobserver agreement, potentially improving the treatment of patients with suspicious microcalcifications and CAC.

Evaluation of PD-1 and interleukin-10-receptor expression by T lymphocytes in malignant and benign pleural effusions

PD-1 (programmed cell death protein-1)/PD-L1 (programmed cell death ligand 1) as well as IL-10 (interleukin-10)/IL-10R (interleukin-10 receptor) interactions play a major role in tumor immune evasion in various malignancies. Several studies investigated the expression of PD-1 on T lymphocytes in pleural effusions (PE) in patients with malignant diseases. However, results in malignant pleural effusions (MPE) compared to benign PE (BPE) are underreported. In this prospective study, 51 patients (median age 66 years, IQR 54–78, 47% male) with PE of malignant or benign origin at the Medical University of Vienna between March 2021 and November 2022 were enrolled and divided into three groups according to the cytological results (group 1: MPE [n = 24, 47%]; group 2: BPE in malignant disease [n = 22, 43%]; group 3: BPE in benign disease [n = 5, 10%]). In the cytological samples, T cells were analyzed for the expression of PD-1 and IL-10R via flow cytometry. In MPE, the proportion of PD-1+ T lymphocytes on CD4+ cells was significantly lower than in BPE (40.1 vs. 56.3 in group 1 vs. 3, p = 0.019). Moreover, a significantly lower expression of PD-1+ IL-10R+ CD8+ (9.6 vs. 35.2 in group 1 vs. 2, p = 0.016; 9.6 vs. 25.0 in group 1 vs. 3, p = 0.032) and a significantly higher expression of PD-1-IL-10R-CD8+ T lymphocytes (43.7 vs. 14.0 in group1 vs. 2, p = 0.045; 43.7 vs. 23.3 in group 1 vs. 3, p = 0.032) were observed in MPE when compared to BPE. The frequency of T cells expressing PD-1 and IL-10R on CD8+ T cells is significantly lower in MPE compared to BPE regardless of the underlying disease indicating a different microenvironment in PE driven by the presence of tumor cells. Our observation spotlights the possible involvement of PD-1 and IL-10R in MPE.

A parasitic leiomyoma of the sigmoid mesentery with schwannoma-like image findings

BackgroundParasitic leiomyoma (PL) consists of uterine fibroids separate from the uterus that grow in extrauterine tissues such as the peritoneum and mesenterium. The diagnosis of PL requires a thorough medical history of laparoscopic myomectomies using a morcellator and the identification of typical magnetic resonance imaging (MRI) findings as uterine fibroids. Imaging diagnosis of PL is occasionally difficult when PL degenerates in various ways, owing to atypical findings on computed tomography (CT) and MRI.Case presentationA 29-year-old woman with a history of laparoscopic myomectomy visited a local hospital with lower abdominal pain. A mesenteric tumor on the sigmoid mesentery was suspected on MRI, and she was referred to our hospital. CT scan showed strong early contrast uptake in the center of the tumor, and MRI T2-weighted images showed high signals at the tumor margins and low signals in the center, suggesting a schwannoma. PL was also part of the differential diagnosis because of the patient’s history of laparoscopic myomectomy. With a preoperative diagnosis of a sigmoid colon mesenteric tumor undeniably of malignant origin, laparoscopic resection of the sigmoid mesenteric tumor was performed. Histopathological examination revealed it to be a PL.ConclusionsWe report a case of PL of the sigmoid mesentery with schwannoma-like findings on imaging that was treated laparoscopically. PL is sometimes difficult to distinguish from schwannomas because of the variety of imaging findings, such as uterine fibroids. PL should be considered in the differential diagnosis of mesenteric tumors following laparoscopic myomectomies, even if it does not show typical imaging findings, such as uterine fibroids.

Oral Cavity Cancer Secondary to Dental Trauma: A Scoping Review.

(1) Background: Oral cavity cancer represents the most common site of origin of head and neck mucosal malignancies. A few limited studies have suggested that chronic irritation, particularly in non-healing ulcers, and fibrotic tissue from poor dentition or ill-fitting dentures had a role in developing mouth cancer. This scoping review aims to evaluate the existing evidence concerning Oral Cavicty Cancer (OCC) in non-smokers/non-drinkers and the relationship with dental trauma. (2) Methods: A scoping review of the PubMed, Embase, and Web of Science databases was completed in adherence with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews checklist. (3) Results: Of the 33 articles that met inclusion, in 6 of them authors discussed the role of topography in dental trauma, in 11 articles authors discussed the carcinogenesis mechanism involved in chronic mucosal trauma, in 17 articles data on ill-fitting dentures was included, 4 studies dealt with the effect of broken/sharp teeth on mucosal damage, and in 7 studies the role of oral hygiene was covered. Less frequently discussed topics included gender, risk of neck nodes, and the role of potentially malignant oral disorders. (4) Conclusions: The available literature suggests a potential connection between chronic dental trauma and the development of OCC. Studies have highlighted factors such as denture use and ill-fitting dental appliances as contributors to an increased risk of oral cancer. Interestingly, we still miss data to support the hypothesis that women, particularly those without toxic habits like smoking or alcohol consumption, appear to be disproportionately affected by oral cancer related to chronic dental trauma.

Hematopoietic stem cell heterogeneity and age-associated platelet bias are evolutionarily conserved.

Hematopoietic stem cells (HSCs) reconstitute multilineage human hematopoiesis after clinical bone marrow (BM) transplantation and are the cells of origin of some hematological malignancies. Although HSCs provide multilineage engraftment, individual murine HSCs are lineage biased and contribute unequally to blood cell lineages. Here, we performed high-throughput single-cell RNA sequencing in mice after xenograft with molecularly barcoded adult human BM HSCs. We demonstrated that human individual BM HSCs are also functionally and transcriptionally lineage biased. Specifically, we identified platelet-biased and multilineage human HSCs. Quantitative comparison of transcriptomes from single HSCs from young and aged BM showed that both the proportion of platelet-biased HSCs and their level of transcriptional platelet priming increase with age. Therefore, platelet-biased HSCs and their increased prevalence and transcriptional platelet priming during aging are conserved features of mammalian evolution.

Anti-tumour activity of Panobinostat in oesophageal adenocarcinoma and squamous cell carcinoma cell lines

BackgroundOesophageal cancer remains a challenging disease with high mortality rates and few therapeutic options. In view of these difficulties, epigenetic drugs have emerged as potential alternatives for patient care. The goal of this study was to evaluate the effect and biological consequences of Panobinostat treatment, an HDAC (histone deacetylase) inhibitor already approved for treatment of patients with multiple myeloma, in oesophageal cell lines of normal and malignant origin, with the latter being representative of the two main histological subtypes: adenocarcinoma and squamous cell carcinoma.ResultsPanobinostat treatment inhibited growth and hindered proliferation, colony formation and invasion of oesophageal cancer cells. Considering HDAC tissue expression, HDAC1 was significantly upregulated in normal oesophageal epithelium in comparison with tumour tissue, whereas HDAC3 was overexpressed in oesophageal cancer compared to non-malignant mucosa. No differences between normal and tumour tissue were observed for HDAC2 and HDAC8 expression.ConclusionsPanobinostat exposure effectively impaired malignant features of oesophageal cancer cells. Because HDAC3 was shown to be overexpressed in oesophageal tumour samples, this epigenetic drug may represent an alternative therapeutic option for oesophageal cancer patients.

HGG-09. CONTRASTING CLINICAL COURSES OF THREE PEDIATRIC PATIENTS WITH PDGFRA AMPLIFIED RADIATION-INDUCED HIGH-GRADE GLIOMA

Abstract BACKGROUND Radiation-induced gliomas (RIG) can occur in 3% of patients receiving cranial radiation. Often, these gliomas are high-grade, treatment refractory, and share common molecular profiles like PDGFRA amplification, regardless of their previous malignant origin. Despite similar genetic alterations, the clinical course of these tumors is varied and not well-studied. Herein, we describe three patients with a PDGRFA-amplified RIG with a particular focus on their contrasting disease course. CASE DESCRIPTION: Our first patient is a now-deceased male diagnosed with medulloblastoma at 5 years of age, treated with surgical resection and craniospinal radiation followed by chemotherapy per COG ACNS0332. Ten years later, he was diagnosed with diffuse pediatric type high-grade-glioma (HGG) in the pons with PDGFA, KIT, MTAP amplification, and CDKN2A/B loss. His condition deteriorated quickly, and he succumbed to his disease in 8 weeks after family decided against further therapies. Our second patient is a now 20-year-old female, initially diagnosed with a craniopharyngioma at 6 years of age and treated with surgical resection and adjuvant radiation therapy. Eleven years later, she developed a diffuse pediatric type HGG in the pons with PDGFRA, MDM2, and MYCN amplification. She was treated with radiation therapy and has had stable disease on serial imaging for 3 years. Our third patient is a now-deceased male diagnosed with a right temporal melanotic neuroectodermal tumor at 5 years of age, treated with surgical resection and craniospinal radiation followed by chemotherapy per POG99701. Fifteen years later, he developed a diffuse pediatric-type HGG in the cerebellum/pons with PDGRFA amplification. He was treated with proton radiation and concurrent oral Temozolomide per COG ACNS0423. His disease progressed on treatment, and he died prior to initiation of a PDGFRA kinase inhibitor (avapritinib). CONCLUSIONS Further investigation into the underlying factors that drive the differing disease course in patients with RIG is needed.

Comparative Evaluation of Chest Ultrasonography and Computed Tomography as Predictors of Malignant Pleural Effusion: A Prospective Study.

Malignant pleural effusion (MPE) is a manifestation of advanced cancer that requires a prompt and accurate diagnosis. Ultrasonography (US) and computed tomography (CT) are valuable imaging techniques for evaluating pleural effusions; however, their relative predictive ability for a malignant origin remains debatable. This prospective study aimed to compare chest US with CT findings as predictors of malignancy in patients with undiagnosed exudative pleural effusion. Fifty-four adults with undiagnosed exudative pleural effusions underwent comprehensive clinical evaluation including chest US, CT, and histopathologic biopsy. Blinded radiologists evaluated the US and CT images for features suggestive of malignancy, based on predefined criteria. Diagnostic performance measures were calculated using histopathology as a reference standard. Of the 54 patients, 33 (61.1%) had MPEs confirmed on biopsy. No significant differences between US and CT were found in detecting parietal pleural abnormalities, lung lesions, chest wall invasion, or liver metastasis. US outperformed CT in identifying diaphragmatic pleural thickening ≥10 mm (33.3% vs. 6.1%, p < 0.001) and nodularity (45.5% vs. 3%, p < 0.001), whereas CT was superior for mediastinal thickening (48.5% vs. 15.2%, p = 0.002). For diagnosing MPE, diaphragmatic nodularity detected by US had 45.5% sensitivity and 100% specificity, whereas CT mediastinal thickening had 48.5% sensitivity and 90.5% specificity. Both US and CT demonstrate reasonable diagnostic performance for detecting MPE, with particular imaging findings favoring a malignant origin. US may be advantageous for evaluating diaphragmatic pleural involvement, whereas CT is more sensitive to mediastinal abnormalities.

The [18F]F-FDG PET/CT Radiomics Classifier of Histologic Subtypes and Anatomical Disease Origins across Various Malignancies: A Proof-of-Principle Study.

We aimed to investigate whether [18F]F-FDG-PET/CT-derived radiomics can classify histologic subtypes and determine the anatomical origin of various malignancies. In this IRB-approved retrospective study, 391 patients (age = 66.7 ± 11.2) with pulmonary (n = 142), gastroesophageal (n = 128) and head and neck (n = 121) malignancies were included. Image segmentation and feature extraction were performed semi-automatically. Two models (all possible subset regression [APS] and recursive partitioning) were employed to predict histology (squamous cell carcinoma [SCC; n = 219] vs. adenocarcinoma [AC; n = 172]), the anatomical origin, and histology plus anatomical origin. The recursive partitioning algorithm outperformed APS to determine histology (sensitivity 0.90 vs. 0.73; specificity 0.77 vs. 0.65). The recursive partitioning algorithm also revealed good predictive ability regarding anatomical origin. Particularly, pulmonary malignancies were identified with high accuracy (sensitivity 0.93; specificity 0.98). Finally, a model for the synchronous prediction of histology and anatomical disease origin resulted in high accuracy in determining gastroesophageal AC (sensitivity 0.88; specificity 0.92), pulmonary AC (sensitivity 0.89; specificity 0.88) and head and neck SCC (sensitivity 0.91; specificity 0.92). Adding PET-features was associated with marginal incremental value for both the prediction of histology and origin in the APS model. Overall, our study demonstrated a good predictive ability to determine patients' histology and anatomical origin using [18F]F-FDG-PET/CT-derived radiomics features, mainly from CT.

Abstract 3872: Multi-ancestral origins of colorectal lesionsMulti-ancestral origins of colorectal lesions

Abstract The widely accepted paradigm that cancer initiation is a monoclonal event has not been definitively resolved. In sporadic cancers this is due to the requirement for longitudinal sampling to study this occult process, which occurs over years to decades. Individuals with familial adenomatous polyposis (FAP) possess a germline APC mutation, leading to hundreds of colonic polyps in adolescence and a 100% lifetime risk of colorectal cancer. Resected colons from FAP patients contain normal mucosa, benign and dysplastic polyps that embed the natural history of colorectal tumorigenesis at different points of malignant progression. Through genome sequencing of 127 independent polyps or mucosa samples from six FAP patients, we characterized the genomic landscape, relative timing of somatic alterations, and clonal dynamics in normal, dysplastic, and invasive colon tissue. Comparison with multi-region sequencing data from FAP patients and sporadic colorectal adenomas and carcinomas indicates similar molecular profiles, with canonical cancer driver genes present across benign and dysplastic premalignant lesions and shared mutational orders. Pairwise sample comparisons and phylogenetic reconstructions revealed extensive heterogeneity and subclonal sharing within a patient’s benign and dysplastic lesions, irrespective of location in the colon. These data imply that polyps were initiated from multiple cells from distinct lineages whose most recent common ancestor arose during development. We corroborate these findings using a mechanistic mathematical model, which infers polyclonality in 100% of benign and 83% of dysplastic samples. Based on these findings, we propose a conceptual model of the multi-ancestral origin of intestinal malignancies. Citation Format: Ryan O. Schenck, Aziz Khan, Aaron Horning, Edward D. Esplin, Debra Van Egeren, HTAN–FAP Consortium, William Greenleaf, James M. Ford, Michael P. Snyder, Christina Curtis. Multi-ancestral origins of colorectal lesionsMulti-ancestral origins of colorectal lesions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3872.

Abstract 3788: EpCAM+ DCCs isolated from the bone marrow of breast cancer patients display high stemness and potency scores

Abstract Metastatic dissemination of cancer cells from primary to distant sites often occurs early and it has been shown that their detection is linked to poor outcomes. Eradication of disseminated cancer cells (DCC) has therefore become the primary goal of adjuvant therapies. Since the phenotype of DCC is largely unknown, we set out to search, isolate, and molecularly characterize these candidate metastasis founder cells from bone marrow of breast cancer patients, years before manifestation of metastasis. We screened more than 200 bone marrow samples of breast cancer patients with no evident metastasis (UICC stage M0) for EpCAM-positive cells. EpCAM positive cells in the bone marrow of healthy donors were used as a negative control. In addition, we isolated DCC from breast cancer patients with manifest metastasis (UICC stage M1). We then performed single cell RNA sequencing after whole transcriptome amplification of the collected DCC and the healthy donor (HD) control cells. To confirm the malignant origin of picked DCCs, we projected the transcriptome data into the bone marrow atlas, inferred copy number alterations, and searched for mutations shared with the matched primary tumor. EpCAM-positive cells from control patients mostly comprised plasma cells. In contrast, DCCs derived from M0-stage breast cancer patient formed a unique, non-overlapping cluster in the bone marrow atlas. UMAP-clustering placed M1-stage DCC clearly separate from M0 stage DCC. Among the collected M0-stage DCCs, we identified at least three separate subclusters. Strikingly, M0-stage DCC displayed much higher stemness and potency scores than M1-stage DCCs, reminiscent of embryonic cells. DCCs, identified by EpCAM, display very high transcriptional stemness scores when isolated before metastatic manifestation. Upon expansion and proliferation, stemness scores are reduced indicating epithelial re-differentiation. The embryonic phenotype of M0-stage DCCs may reflect an early adaptive mechanism that enables DCC to survive in an ectopic environment and may impact on the metastatic potential of the DCC. Citation Format: Elia Raya, Huiqin Koerkel-Qu, Laura Rudhart, Lisa-Marie Köhler, Anna Damboeck, Christoph Irlbeck, Catherine Botteron, Melanie Werner-Klein, Stephan Seitz, Christoph Klein. EpCAM+ DCCs isolated from the bone marrow of breast cancer patients display high stemness and potency scores [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3788.

Abstract 3709: Single cell analysis from CSF of patients with suspected leptomeningeal metastasis

Abstract Introduction: Leptomeningeal metastases (LM) are diagnosed in up to 10% of metastatic cancer patients, the most frequent cancers being carcinomas of breast and lung or melanoma. Due to a dismal prognosis and an overall median survival of only four months new approaches for molecular analysis could help to identify individual treatment options. Material and Methods: In this study, we collected 28 cerebrospinal fluid (CSF) samples from patients with different primary tumors but suspected LM. CSF was divided in two parts for standard neuropathologic cytomorphology and detection of circulating tumor cells (CTCs) by using the CellSearch® CTC Kit, respectively. Subsequently, single Cytokeratin-positive CTCs were isolated for whole genome amplification by Ampli1TM and molecular analysis. Additionally, we were able to isolate cell-free DNA (cfDNA) from CSF in a subset of patients which we amplified by an adapted Ampli1TM library protocol. In a small subset of patients, we collected slices of formalin-fixed paraffin embedded (FFPE) primary tumors and systemic metastases for dissociation and isolation of pure subpopulations by DEPArrayTM technology. Isolated CTCs, cfDNA and subpopulations of tumor and stromal cells were analyzed for copy number variations (CNV) applying the Ampli1TM LowPass protocol on the Illumina MiSeqTM platform. Results: By comparing results from classical cytomorphology and CellSearch® workflow, we could find high concordance (24/28 samples) with a slightly higher tumor cell detection rate by CellSearch® (11 positive cases vs. 9 by cytomorphology). Importantly, we could confirm the malignant origin of isolated cells by CNV analysis in all patients positive in CellSearch® assay. Moreover, by comparing single cell data with cfDNA analysis of a subset of 20 samples, we could also detect a higher sensitivity for tumor detection in CTC-based analysis (8/20 cases positive) in comparison to cfDNA-based analysis (5/20 cases positive). In a comprehensive analysis of multiple samples of an individual patient, including CTCs and cfDNA from CSF at different time points, CTCs from blood and biopsies from multiple visceral metastasis, we could identify divergent genomic evolution between tumor cells from the central nervous syste Conclusion: In this proof-of-concept study we show that a liquid biopsy-based approach for single cell analysis from CSF holds potential for innovative diagnostic assays for patients with suspected LM. Combining CTC quantification with molecular single cell analysis could enable us to define predictive tests to select novel treatment options for patients with LM in the future. Citation Format: Caecilia Koestler, Giancarlo Feliciello, Florian Lueke, Kathrin Weidele, Saida Zoubaa, Peter Hau, Tobias Pukrop, Markus J. Riemenschneider, Christoph A. Klein, Bernhard Polzer. Single cell analysis from CSF of patients with suspected leptomeningeal metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3709.

Origins of Second Malignancies in Children and Mutational Footprint of Chemotherapy in Normal Tissues.

Using whole-genome and error-correcting ultra-deep duplex sequencing, we uncover different origins for second neoplasms in four children. We also uncover the presence of platinum-related mutations across 10 normal tissues of exposed individuals, highlighting the impact that the use of cytotoxic therapies may have on cancer survivors. See related commentary by Pacyna and Nangalia, p. 900. This article is featured in Selected Articles from This Issue, p. 897.

Prevalence and Clinical Management of Adrenal Tumour-Related Hyperandrogenism: A Narrative Review.

Hyperandrogenism is a condition in which the levels of androgen hormones in the blood are significantly increased and could be of an adrenal or ovarian origin. The adrenal androgens, normally secreted by the zona reticularis, are steroid hormones with weak androgen activity. The causes of hyperandrogenism are diverse and could be endogenous and exogenous. Androgen excess affecting different tissues and organs results in clinical features such as acne, hirsutism, virilization, and reproductive dysfunction such as oligomenorrhoea/amenorrhoea. Although androgen excess is rarely associated with adrenal tumours, it is important as it could be predictive of malignancy. A careful evaluation of the androgen pattern, also in patients with clear signs of hyperandrogenism, could be useful. Laboratory evaluation should focus on measuring total testosterone levels, followed by the estimation of other androgens such as dehydroepiandrosterone and androstenedione, and using visualisation procedures in the further management. The treatment of adrenal hyperandrogenism is eminently surgical, in consideration of the frequent malignant origin. The aim of this review is to elaborate and summarize the prevalence and clinical management of hyperandrogenism of an adrenal origin by describing the physiological mechanisms of adrenal androgen steroidogenesis, the clinical manifestations of hyperandrogenism with a special reference to hyperandrogenism in adrenal adenomas and carcinomas, and the diagnostic methods that will lead us to establishing the correct diagnosis and different treatment options to manage this condition according to the clinical presentation of the patient.

Contrast-enhanced Chest Ultrasound – Modern Achievements of Pulmonology in Bulgaria

Contrast-enhanced ultrasound (CEUS) is an innovative imaging method in pulmonology based on the intravenous administration of a contrast medium in the form of microspheres, and the subsequent detailed representation of the perfusion characteristics of the target tissues. The method allows the distinction between malignant and benign origin of a given pathological lesion. The purpose of the current article is to introduce to the scientific society the modern achievements of contrast-enhanced ultrasound of the thorax in pulmonology in Bulgaria. We present twenty-seven clinical cases from the period 2017--2020, in which CEUS was applied at different stages of the diagnostic process. The results are compared with a previous survey conducted in Bulgaria in 2011.

Peritoneal Carcinomatosis of Malignant Gynecological Origin: A Systematic Review of Imaging Assessment.

This systematic review, conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol, aims to comprehensively assess the current state of the art of imaging modalities for the evaluation of peritoneal carcinomatosis arising from malignant gynecological origins, with a focus on ovarian and endometrial cancers. A systematic search of relevant databases was performed, adhering to predetermined inclusion and exclusion criteria. Studies reporting the use of computed tomography (CT), magnetic resonance imaging (MRI), fluorodeoxyglucose (FDG) positron emission tomography (PET), PET/CT, and PET/MRI in the assessment of peritoneal carcinomatosis from gynecological malignancies were included. The review encompasses an overview of selected studies, highlighting the strengths and limitations of each imaging modality in diagnosing and characterizing peritoneal carcinomatosis. Overall, a wide variability in the reported accuracy of different imaging techniques emerges from literature, mainly due to the type of the study, technical issues, and patient characteristics. Although a meta-analysis could not be performed due to a scarcity of data, this systematic review provides valuable insights into the several imaging approaches used in peritoneal carcinomatosis of gynecological origin. The findings aim to inform clinical decision making and guide future research endeavors in this critical aspect of gynecological oncology.

Abstract B008: The polyclonal path towards malignant transformation in familial adenomatous polyposis

Abstract The widely accepted paradigm that cancer initiation is a monoclonal event has not been definitively resolved. This is largely due to the limitations of experimental systems to study cancer initiation, a definitively transient step in tumorigenesis. Individuals with familial adenomatous polyposis (FAP) possess a germline APC mutation, leading to hundreds of colonic polyps in adolescence and an eventual 100% lifetime risk of colorectal cancer. As such, total colectomies are performed once polyp burden becomes unmanageable and provide the resected colons from FAP donors provide a source of histologically normal mucosa, benign and dysplastic polyps, and, on rare occasions, adenocarcinomas, and serve as an exemplary model disease to understand human tumorigenesis. Through whole genome sequencing of 123 independent samples from six patients, we reveal the polyclonal origins of tumorigenesis in FAP. We characterize and contrast the genomic landscape and relative timing of driver mutation acquisition across normal to dysplastic and invasive colon tissue and compare this with multi-region sequencing data from sporadic colorectal cancers (CRC). We find that only early sporadic CRC drivers are common across the more heterogeneous premalignant stages. Selection, as assessed based on the ratio of nonsynonymous to synonymous mutations (dN/dS), is higher in benign than dysplastic FAP lesions and in sporadic adenomas relative to carcinomas. Phylogenetic reconstruction and pairwise sample comparisons reveal extensive heterogeneity and subclonal sharing within a patient’s benign and dysplastic lesions. Using a mechanistic mathematical model, we infer polyclonality for 90-100% of benign and 53-83% of dysplastic samples. Based on these findings, we propose a conceptual framework for the polyclonal origin of intestinal malignancies where inconsequential mutations, arising during colon formation in utero, are present across the colon and are valuable markers to uncover polyclonal ancestry. Citation Format: Ryan O. Schenck, Aziz Khan, Aaron M. Horning, Edward D. Esplin, HTAN Consortia, William J. Greenleaf, James M. Ford, Michael P. Snyder, Christina Curtis. The polyclonal path towards malignant transformation in familial adenomatous polyposis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr B008.

Surgical treatment of malignant right coronary artery origin

Surgical treatment of malignant right coronary artery origin

Microbiological and Molecular Study of Paranasal Sinus Infections of Children with Malignancy and Unknown Origin Fever in Markazi Province, Iran

BackgroundChildren with malignancies are vulnerable to various infections, including sinus infections. Sinusitis is primarily caused by bacterial infections, followed by fungal infections. Due to this issue, evaluating the occurrence, diversity, and antibiotic susceptibility patterns of bacterial species that cause paranasal sinus infections in children with malignancy and unexplained fever is important. ObjectiveInvestigate the bacterial species accountable for sinusitis in children with malignancy and unexplained fever, and determine their susceptibility to antibiotics. MethodsThe study involved collecting 90 sinus samples from children aged 5-15 years with malignancy in Arak city. The isolates were identified using a combination of phenotypic, biochemical, and molecular techniques, including specific PCR and 16S rRNA gene sequencing. drug susceptibility testing was performed following the CLSI 2021 guidelines. ResultsA total of 36 isolates (40%) were obtained, including 4 isolates of Nocardia (11.12%), 4 isolates of E. coli (11.12%), 3 isolates of K. pneumoniae (8.33%), 5 isolates of P. aeruginosa (13.88%), 3 isolates of A. baumannii (8.33%), 4 isolates of S. aureus (11.12%), 3 isolates of S. epidermidis (8.33%), 5 isolates of S. agalactiae (13.88%), 2 isolates of S. pneumoniae (5.55%), and 3 isolates of E. faecium (8.33%). The isolates showed the most sensitivity to imipenem and trimethoprim-sulfamethoxazole and the least sensitivity to erythromycin and tetracycline. ConclusionsThe findings of the study indicate that sinusitis can contribute to fever of unknown origin in cancer patients. Therefore, it is recommended to use a combination of molecular and phenotypic methods for accurate identification of isolates. This approach can provide more reliable and precise results, leading to better diagnosis and treatment of sinusitis infections in children with malignancy.