Hasil untuk "Cytology"

Ana S. Formas-Oliveira, Mariana Valentim Ferreira, Ana Sofia Coroadinha

The use of lentiviral vectors (LVs) in gene therapy is expanding, demanding high-quality viral preparations. Producer cell lines for LV production offer robust manufacturing platforms. However, their development is still progressing and more knowledge on the impact of vector components expression levels on vector yields and quality is essential. This work studies the impact of vector cassette expression and stability on vector titer and quality, identifying key parameters in cell line development. Ten heterogeneous LV stable producer clones established through random cassette integration were characterized. The gag-pol and rev cassettes, expressed under the control of constitutive promoters, showed robust expression generating titers of 109 physical particles (P.P.s)/mL. However, Pol and reverse transcriptase expressions were shown to be better indicators of potential functional titers. Envelope and transfer vector expression levels were key to attaining high functional particles yields. The stability analysis of two top clones and their trans-complementation with each genetic cassette further supported this conclusion. The producer LV clones expressed constitutively the 4070A envelope, but the overexpression of the VSV-G envelope increased 30-fold the titer supporting the envelope as key determinant in LV quality. This work further elucidates bottlenecks in LV producer cell line development providing insights for their optimization.

David Glavaš Weinberger, Lena Kotrulja, Snježana Ramić et al.

<b>Background and clinical significance:</b> Osteonecrosis of the femoral head (ONFH) is a disease of the epiphysis caused by the death of osteocytes and osteoblasts, resulting in debilitating pain. ONFH can be traumatic or nontraumatic, with prolonged glucocorticoid use being the leading cause of nontraumatic ONFH. Atopic dermatitis (AD) is a chronic inflammatory skin condition typically treated with topical corticosteroids. ONFH following topical corticosteroid treatment is exceedingly rare, with limited documentation in the literature. We present a case of an under-recognized complication of prolonged topical corticosteroid treatment. <b>Case presentation:</b> We report a case of a 29-year-old Caucasian male patient with sharp right hip pain. Plain radiographs, a CT scan, and an MRI indicated Ficat and Arlet stage 3 ONFH. The patient reported the prolonged uncontrolled use of topical mometasone furoate for five years due to AD. Following the diagnosis, topical corticosteroids were discontinued, and the treatment was shifted to tacrolimus and, subsequently, to oral methotrexate with folic acid. The patient underwent a total hip arthroplasty in June 2022. Given his young age and poor response to previous treatments, he was transitioned to upadacitinib, which led to significant improvement without skin flare-ups or postoperative hip pain. <b>Conclusions:</b> This case highlights the rare, but serious, risk of ONFH associated with long-term topical corticosteroid use. It underscores the importance of monitoring systemic side effects in dermatological therapies and educating patients on proper corticosteroid use. Alternative treatments, such as upadacitinib, should be considered in young male patients to prevent severe complications.

Yuting Ji, Shujing Du, Jingjing Li et al.

Abstract Dysregulation of cell death plays a critical role in the onset and progression of numerous human diseases. Distinct forms of regulated cell death, such as necroptosis and ferroptosis, have been implicated in the pathogenesis of various conditions, including neurodegenerative disorders and acute kidney injury. Strategies that concurrently target both necroptosis and ferroptosis present significant potential for improving therapeutic outcomes. In this study, we identified Zharp1-163 as a dual inhibitor of ferroptosis and necroptosis in both human and mouse species. Zharp1-163 effectively blocks ferroptosis by reducing reactive oxygen species (ROS) levels and inhibits necroptosis by potently and selectively targeting RIPK1 kinase activity. In vivo, Zharp1-163 markedly attenuated TNF-α-induced systemic inflammatory syndrome, including the prevention of TNF-α-induced mortality and hypothermia in mice. Notably, Zharp1-163 significantly alleviated acute kidney injury associated with both necroptosis and ferroptosis in models induced by cisplatin treatment and ischemia-reperfusion. Collectively, our findings establish Zharp1-163 as a dual-action inhibitor capable of effectively suppressing both ferroptosis and necroptosis. These findings highlight its great potential in the treatment of diseases associated with these cell death pathways, such as kidney disease.

Shanqin Qi, Haiyan Yu, Wen Hu et al.

Abstract This article aimed to evaluate the representativeness and sustainability of a rat model of polycystic ovary syndrome (PCOS) induced by letrozole (LE) with or without a high-fat diet (HFD). Sexually mature SD rats were randomly divided into a sham group (receiving 1% carboxymethyl cellulose sodium + standard chow, n = 9), a letrozole group (receiving LE + standard chow, n = 15), and a letrozole combined with HFD group (receiving LE + HFD, n = 15). After 21 days, model tests were performed based on body weight, estrous cycle, hormone levels, and ovarian histological changes, and successful modeling rats in LE and LE + HFD groups were further divided into two subgroups: an induction continuation group and an induction termination group (n = 6 in each group), respectively, which were treated for an additional 5 weeks. Changes in body weight, hormone levels, metabolic parameters, vaginal cytology, and ovarian histology were compared among the groups. Following 21 days of induction, the LE group exhibited significant differences in body weight, serum testosterone concentration, estrous cycle, and ovarian tissue morphology. The LE + HFD group showed significant increases in serum lipid and insulin levels. Upon subdivision, the PCOS phenotype in the letrozole continuation induction group (LE-con group) persisted, while it gradually subsided in the termination group (LE-ter group). Body weight, fasting insulin levels, and the homeostasis model assessment of insulin resistance index in the LE + HFD induction continuation group (LE + HFD-con group) were notably higher than those in the LE-con group, and ovarian histology were more severely disrupted. In conclusion, the LE + HFD induced rats more closely mimic the pathological characteristics of clinical PCOS and thus represent a more representative model compared to those induced by LE alone. However, both models tend to recover after discontinuation, indicating that medication should be continued during subsequent treatment to ensure the sustainability of the models.

Ludovica Barone, Maria Teresa Palano, Matteo Gallazzi et al.

Abstract Tissue regeneration or healing both require efficient vascularization within a tissue-damaged area. Based on this concept, a remarkable number of strategies, aimed at developing new tools to support re-vascularization of damaged tissue have emerged. Among the strategies proposed, the use of pro-angiogenic soluble factors, as a cell-free tool, appears as a promising approach, able to overcome the issues concerning the direct use of cells for regenerative medicine therapy. Here, we compared the effectiveness of adipose mesenchymal stem cells (ASCs), use as cell suspension, ASC protein extract or ASC-conditioned-medium (i.e., soluble factors), combined with collagenic scaffold, in supporting in vivo angiogenesis. We also tested the capability of hypoxia in increasing the efficiency of ASC to promote angiogenesis, via soluble factors, both in vivo and in vitro. In vivo studies were performed using the Integra® Flowable Wound Matrix, and the Ultimatrix in sponge assay. Flow cytometry was used to characterize the scaffold- and sponge-infiltrating cells. Real-time PCR was used to evaluate the expression of pro-angiogenic factors by stimulating Human Umbilical-Vein Endothelial Cells with ASC-conditioned media, obtained in hypoxic and normoxic conditions. We found that, in vivo, ACS-conditioned media can support angiogenesis similar to ASCs and ASC protein extract. Also, we observed that hypoxia increases the pro-angiogenic activities of ASC-conditioned media, compared to normoxia, by generating a secretome enriched in pro-angiogenic soluble factors, with bFGF, Adiponectine, ENA78, GRO, GRO-a, and ICAM1-3, as most regulated factors. Finally, ASC-conditioned media, produced in hypoxic condition, induce the expression of pro-angiogenic molecules in HUVECs. Our results provide evidence that ASC-conditioned-medium can be proposed as a cell-free preparation able to support angiogenesis, thus providing a relevant tool to overcome the issues and restrictions associated with the use of cells.

Tatiana J. Carneiro, Ana L. M. Batista Carvalho, Martin Vojtek et al.

Abstract This work compared the metabolic profile of a parental MDA-MB-231 cisplatin-sensitive triple negative breast cancer (TNBC) cell line with that of a derived cisplatin-resistant line, to characterize inherent metabolic adaptations to resistance, as a means for marker and new TNBC therapies discovery. Supported by cytotoxic, microscopic and biochemical characterization of both lines, Nuclear Magnetic Resonance (NMR) metabolomics was employed to characterize cell polar extracts for the two cell lines, as a function of time (0, 24 and 48 h), and identify statistically relevant differences both between sensitive and resistant cells and their time course behavior. Biochemical results revealed a slight increase in activation of the NF-κB pathway and a marked decrease of the ERK signaling pathway in resistant cells. This was accompanied by lower glycolytic and glutaminolytic activities, possibly linked to glutamine being required to increase stemness capacity and, hence, higher survival to cisplatin. The TCA cycle dynamics seemed to be time-dependent, with an apparent activation at 48 h preferentially supported by anaplerotic aromatic amino acids, leucine and lysine. A distinct behavior of leucine, compared to the other branched-chain-amino-acids, suggested the importance of the recognized relationship between leucine and in mTOR-mediated autophagy to increase resistance. Suggested markers of MDA-MB-231 TNBC cisplatin-resistance included higher phosphocreatine/creatine ratios, hypotaurine/taurine–mediated antioxidant protective mechanisms, a generalized marked depletion in nucleotides/nucleosides, and a distinctive pattern of choline compounds. Although the putative hypotheses generated here require biological demonstration, they pave the way to the use of metabolites as markers of cisplatin-resistance in TNBC and as guidance to develop therapies.

Vignesh Jayarajan, George T. Hall, Theodoros Xenakis et al.

Primary keratinocytes including keratinocyte stem cells (KSCs) can be cultured as epidermal sheets <i>in vitro</i> and are attractive for cell and gene therapies for genetic skin disorders. However, the initial slow growth of freshly isolated keratinocytes hinders clinical applications. Rho-associated kinase inhibitor (ROCKi) has been used to overcome this obstacle, but its influence on the characteristics of KSC and its safety for clinical application remains unknown. In this study, primary keratinocytes were treated with ROCKi Y-27632 for six days (short-term). Significant increases in colony formation and cell proliferation during the six-day ROCKi treatment were observed and confirmed by related protein markers and single-cell transcriptomic analysis. In addition, short-term ROCKi-treated cells maintained their differentiation ability as examined by 3D-organotypic culture. However, these changes could be reversed and became indistinguishable between treated and untreated cells once ROCKi treatment was withdrawn. Further, the short-term ROCKi treatment did not reduce the number of KSCs. In addition, AKT and ERK pathways were rapidly activated upon ROCKi treatment. In conclusion, short-term ROCKi treatment can transiently and reversibly accelerate initial primary keratinocyte expansion while preserving the holoclone-forming cell population (KSCs), providing a safe avenue for clinical applications.

Poonam Sharma, Rajat Gupta, Subhash Bhardwaj

Background: Cutaneous metastases are quite rare and represent growth of malignant cells in skin from an internal malignancy and indicate poor prognosis. Fine needle aspiration cytology (FNAC) is an important technique in the early diagnosis of such lesions. Objective: To evaluate the cytomorphological features of cutaneous metastatic nodules on FNAC. Material and Methods: This retrospective diagnostic analytical study was carried out in the department of pathology from January 2016 to December 2020. Forty-Four patients diagnosed as cutaneous metastasis on FNAC were included in the study. FNAC slides along with record of the patients were retrieved and findings recorded. The smears were examined in detail for cytomorphological evaluation. Results: 26 patients were males and 18 were females with M:F ratio of 1.4:1. The site of primary malignancy was known in 32 cases only. Chest wall was the commonest site of cutaneous metastasis, with solitary palpable skin nodule being the commonest clinical presentation. In patients with known primary, lung carcinoma and breast carcinoma were the commonest primary malignancy in males and females respectively. Metastatic adenocarcinoma was the commonest cytomorphological type of malignancy (31.8%) followed by squamous cell carcinoma (SCC). FNAC diagnosis helped in detecting the primary site in 5 (41.6%) out of 12 cases with unknown primary malignancy. Conclusions: FNAC is an easy, rapid and minimally invasive procedure in the diagnosis of cutaneous metastases.

Samantha C. Faber, Tejas S. Lahoti, Ewan R. Taylor et al.

Target modulation of the AhR for inflammatory gastrointestinal (GI) conditions holds great promise but also the potential for safety liabilities both within and beyond the GI tract. The ubiquitous expression of the AhR across mammalian tissues coupled with its role in diverse signaling pathways makes development of a “clean” AhR therapeutically challenging. Ligand promiscuity and diversity in context-specific AhR activation further complicates targeting the AhR for drug development due to limitations surrounding clinical translatability. Despite these concerns, several approaches to target the AhR have been explored such as small molecules, microbials, PROTACs, and oligonucleotide-based approaches. These various chemical modalities are not without safety liabilities and require unique de-risking strategies to parse out toxicities. Collectively, these programs can benefit from in silico and in vitro methodologies that investigate specific AhR pathway activation and have the potential to implement thresholding parameters to categorize AhR ligands as “high” or “low” risk for sustained AhR activation. Exploration into transcriptomic signatures for AhR safety assessment, incorporation of physiologically-relevant in vitro model systems, and investigation into chronic activation of the AhR by structurally diverse ligands will help address gaps in our understanding regarding AhR-dependent toxicities. Here, we review the role of the AhR within the GI tract, novel therapeutic modality approaches to target the AhR, key AhR-dependent safety liabilities, and relevant strategies that can be implemented to address drug safety concerns. Together, this review discusses the emerging therapeutic landscape of modalities targeting the AhR for inflammatory GI indications and offers a safety roadmap for AhR drug development.

Simone Minasi, Daniela Bosco, Bernardo Moretti et al.

Urine cytology is a non-invasive test used in combination with cystoscopy for screening and follow-up of urothelial carcinoma (UC). Although cytology can be used to efficiently identify high-grade UC, it has a lower accuracy for the diagnosis of low-grade UC or patients with presence of atypical urothelial cells (AUC). For these reasons, ancillary tests have been added to urine cytology in order to improve the accuracy. However, the poor abundance of neoplastic cells in most samples and the absence of a “tissue-like” structure remains a major challenge. We used a novel synthetic support called CytoMatrix which has the property of capturing and storing cells and micro-macro aggregates within its three-dimensional structure. The urine specimens were obtained from 12 patients: 6 with suspected urothelial neoplasia (low- and high-grade) and 6 with AUC or non-neoplastic samples. The first step is the urine samples preparation, through several centrifugation passages; the second step consists in absorbing cells on the CytoMatrix, and in the subsequent formalin fixation, standard processing and paraffin embedding to prepare FFPE-CytoMatrix block. In the final step, sections are consecutively cut, stained with hematoxylin-eosin (H&E), and analyzed via UroVysion FISH and immunohistochemistry (IHC). Using our simple and reliable protocol, we can improve the quality of urine specimens, allowing a better collection, maintenance, and analysis of cells, with the advantage of using ancillary tests to support cytological diagnosis and the advantage of storing cellular material in a FFPE-CytoMatrix block.

Huan Zhang, Huanji Xu, Chenliang Zhang et al.

Abstract The Hippo/YAP pathway plays an important role in the development of cancers. Previous studies have reported that bile acids can activate YAP (Yes Associated Protein) to promote tumorigenesis and tumor progression. Ursodeoxycholic acid (UDCA) is a long-established old drug used for cholestasis treatment. So far, the effect of UDCA on YAP signaling in colorectal cancer (CRC) is not well defined. This study means to explore relationship of UDCA and YAP in CRC. UDCA suppressed YAP signaling by activating the membrane G-protein-coupled bile acid receptor (TGR5). TGR5 mainly regulated cAMP/PKA signaling pathway to inhibit RhoA activity, thereby suppressing YAP signaling. Moreover, the restoration of YAP expression alleviated the inhibitory effect of UDCA on CRC cell proliferation. In AOM/DSS-induced CRC model, UDCA inhibited tumor growth in a concentration-dependent manner and decreased expression of YAP and Ki67. UDCA plays a distinguished role in regulating YAP signaling and CRC growth from the primary bile acids and partial secondary bile acids, demonstrating the importance of maintaining normal intestinal bile acid metabolism in cancer patients. It also presents a potential therapeutic intervention for CRC.

Eleonora Starikova, Jennet Mammedova, Arina Ozhiganova et al.

Acute liver injury in its terminal phase trigger systemic inflammatory response syndrome with multiple organ failure. An uncontrolled inflammatory reaction is difficult to treat and contributes to high mortality. Therefore, to solve this problem a search for new therapeutic approaches remains urgent. This study aimed to explore the protective effects of M. edulis hydrolysate (N2-01) against Lipopolysaccharide-D-Galactosamine (LPS/D-GalN)-induced murine acute liver injure and the underlying mechanisms. N2-01 analysis, using Liquid Chromatography Mass Spectrometry (LCMS) metabolomic and proteomic platforms, confirmed composition, molecular-weight distribution, and high reproducibility between M. edulis hydrolysate manufactured batches. N2-01 efficiently protected mice against LPS/D-GalN-induced acute liver injury. The most prominent result (100% survival rate) was obtained by the constant subcutaneous administration of small doses of the drug. N2-01 decreased Vascular Cell Adhesion Molecule-1 (VCAM-1) expression from 4.648 ± 0.445 to 1.503 ± 0.091 Mean Fluorescence Intensity (MFI) and Interleukin-6 (IL-6) production in activated Human Umbilical Vein Endothelial Cells (HUVECs) from 7.473 ± 0.666 to 2.980 ± 0.130 ng/ml in vitro. The drug increased Nitric Oxide (NO) production by HUVECs from 27.203 ± 2.890 to 69.200 ± 4.716 MFI but significantly decreased inducible Nitric Oxide Synthase (iNOS) expression from 24.030 ± 2.776 to 15.300 ± 1.290 MFI and NO production by murine peritoneal lavage cells from 6.777 ± 0.373 µm to 2.175 ± 0.279 µm. The capability of the preparation to enhance the endothelium barrier function and to reduce vascular permeability was confirmed in Electrical Cell-substrate Impedance Sensor (ECIS) test in vitro and Miles assay in vivo. These results suggest N2-01 as a promising agent for treating a wide range of conditions associated with uncontrolled inflammation and endothelial dysfunction.

Wentao Ma, Weihong Zhang, Bing Cui et al.

Abstract The delivery of biomolecules by extracellular vesicles (EVs) derived from endothelial progenitor cells (EPCs) has been proven to ameliorate sepsis, yet the therapeutic mechanism remains to be elucidated. Taurine upregulated gene 1 (TUG1) is a long noncoding RNA (lncRNA) that is downregulated in sepsis. The current study was designed to explore the role of EPCs derived EVs transmitting TUG1 in macrophage polarization and macrophage-mediated inflammation in a cecal ligation and puncture (CLP)-induced sepsis mouse model. TUG1 was underexpressed in CLP-induced sepsis, and its reexpression induced anti-inflammatory macrophage polarization and suppressed macrophage-medicated inflammatory injury to the pulmonary vascular endothelium. EPCs derived EVs transmitted TUG1 to promote M2 macrophage polarization. Luciferase, RIP, and RNA pull-down assays showed that TUG1 could competitively bind to microRNA-9-5p (miR-9-5p) to upregulate the expression of sirtuin 1 (SIRT1). Furthermore, EPCs derived EVs transmitted TUG1 to promote M2 macrophage polarization through the impairment of miR-9-5p-dependent SIRT1 inhibition. Finally, EPCs derived EVs carrying TUG1 were verified to ameliorate sepsis-induced organ damage in the murine model. In summary, EPCs derived EVs transmit TUG1 to attenuate sepsis via macrophage M2 polarization. This study also highlights the proinflammatory mechanism associated with miR-9-5p-mediated inhibition of SIRT1, which contributes to a more comprehensive understanding of the pathogenesis of sepsis.

Philip Dao Trong, Gerhard Jungwirth, Tao Yu et al.

The discovery of the isocitrate dehydrogenase (IDH) mutation in glioma led to a paradigm shift on how we see glioma biology. Difficulties in cultivating IDH mutant glioma stem cells (IDH^mut GSCs) resulted in a paucity of preclinical models in IDH^mut glioma, limiting the discovery of new effective chemotherapeutic agents. To fill this gap, we used six recently developed patient-derived IDH^mut GSC lines and performed a large-scale drug screening with 147 Food and Drug Administration (FDA)-approved anticancer drugs. GSCs were subjected to the test compounds for 72 h in concentrations ranging from 0.0001 to 1 µM. Cell viability was assessed by CellTiterGlo and the induction of apoptosis by flow cytometry with Annexin V/propidium iodide staining. The initial screen was performed with two IDH^mut GSC lines and identified seven drugs (bortezomib, carfilzomib, daunorubicin, doxorubicin, epirubicin, omacetaxine, plicamycin) with a substantial antiproliferative activity, as reflected by half maximal inhibitory concentrations (IC₅₀) below 1 µM and maximum inhibitory effects (E_max) below 25%. These findings were validated in an additional four IDH^mut GSC lines. The candidate drugs, of which plicamycin and omacetaxine are known to cross the blood brain barrier, were used for subsequent cell death analyses. A significant induction of apoptosis was observed at IC₅₀ values of the respective drugs. In summary, we were able to identify seven FDA-approved drugs that should be further taken into clinical investigations for the treatment of IDH^mut gliomas.

Yunxiang Yang, Pan Yang, Nan Wang et al.

Abstract Genome packaging is a fundamental process in a viral life cycle and a prime target of antiviral drugs. Herpesviruses use an ATP-driven packaging motor/terminase complex to translocate and cleave concatemeric dsDNA into procapsids but its molecular architecture and mechanism are unknown. We report atomic structures of a herpesvirus hexameric terminase complex in both the apo and ADP•BeF3-bound states. Each subunit of the hexameric ring comprises three components—the ATPase/terminase pUL15 and two regulator/fixer proteins, pUL28 and pUL33—unlike bacteriophage terminases. Distal to the nuclease domains, six ATPase domains form a central channel with conserved basic-patches conducive to DNA binding and trans-acting arginine fingers are essential to ATP hydrolysis and sequential DNA translocation. Rearrangement of the nuclease domains mediated by regulatory domains converts DNA translocation mode to cleavage mode. Our structures favor a sequential revolution model for DNA translocation and suggest mechanisms for concerted domain rearrangements leading to DNA cleavage.

Hye Ji Choi, Hyun Jae Lee, Jin Young Choi et al.

The His723Arg (H723R) mutation in SLC26A4, encoding pendrin, is the most prevalent mutation in East Asia, resulting in DFNB4, an autosomal recessive type of genetic hearing loss. Although the main pathological mechanism of H723R was identified as a protein-folding defect in pendrin, there is still no curative treatment for associated hearing loss. Here, we show that H723R-pendrin expression and activity are rescued by activation of the chaperonin DNAJC14. In vitro, DNAJC14 was activated via Japanese encephalitis virus (JEV) inoculation, and toxin-attenuated JEV rescued the surface expression and anion exchange activity of H723R-pendrin. Human H723R-pendrin transgenic mice (hH723R Tg) were established in a mouse slc26a4 knockout background, in which only hH723R-pendrin was expressed in the inner ear (Pax2-Cre dependent) to mimic human DFNB4 pathology. Crossing hH723R Tg with DNAJC14-overexpressing mice resulted in reduced cochlear hydrops and more preserved outer hair cells in the cochlea compared to those in hH723R Tg mice. Furthermore, the stria vascularis and spiral ligament were thicker and KCNJ10 expression was increased with DNAJC14 overexpression; however, hearing function and enlarged endolymphatic hydrops were not recovered. These results indicate that DNAJC14 overexpression ameliorates the cochlear degeneration caused by misfolded pendrin and might be a potential therapeutic target for DFNB4.

Flavio L. Ronzoni, Sylvain Lemeille, Rostyslav Kuzyakiv et al.

Abstract Mesoangioblasts (MABs) derived from adult skeletal muscles are well‐studied adult stem/progenitor cells that already entered clinical trials for muscle regeneration in genetic diseases; however, the transcriptional identity of human fetal MABs (fMABs) remains largely unknown. Herein we analyzed the transcriptome of MABs isolated according to canonical markers from fetal atrium, ventricle, aorta, and skeletal muscles (from 9.5 to 13 weeks of age) to uncover specific gene signatures correlating with their peculiar myogenic differentiation properties inherent to their tissue of origin. RNA‐seq analysis revealed for the first time that human MABs from fetal aorta, cardiac (atrial and ventricular), and skeletal muscles display subsets of differentially expressed genes likely representing distinct expression signatures indicative of their original tissue. Identified GO biological processes and KEGG pathways likely account for their distinct differentiation outcomes and provide a set of critical genes possibly predicting future specific differentiation outcomes. This study reveals novel information regarding the potential of human fMABs that may help to improve specific differentiation outcomes relevant for therapeutic muscle regeneration.

N. Paul Ohori

Ankica Vasilj, Sandra Kojić Katović

The aim of the study was to assess the role of fine needle aspiration cytology (FNAC) in the diagnosis of focal changes in solid abdominal organs. A total of 1084 aspirates from intra-abdominal organs including liver, spleen, pancreas and kidneys obtained by ultrasound (US) guidance during a 10-year period were included in the study. The smears were classified as benign, malignant or suspected of malignancy, and unsatisfactory for interpretation. The liver accounted for more than half of the US-guided FNA procedures, followed by the pancreas with 38%. Out of 1084 aspirations, 192 (17.7%) were inadequate for cytologic analysis. Over half of aspirated lesions in the pancreas were primary cancers, while one-third of pancreatic lesions were benign. In the majority of kidney lesions (83%), cytology found benign changes, mostly cysts. Spleen FNA was least likely; in most cases (59%) it showed lymphoid tissue hyperplasia; in four cases cytologic diagnosis was lymphoma and three lesions were suspected lymphoma. During the study, no major complications were observed on any US-guided FNAC procedure. In conclusion, intra-abdominal FNA is a reliable, sensitive and specific method with a high diagnostic accuracy for the diagnosis of malignant lesions. It can be utilized as a preoperative procedure for the management of all intra-abdominal lesions.

P.H. Bartels, J. Layton, R.L. Shoemaker