Neoplastic Liver Research Articles

The Rationale for Combining Normothermic Liver Machine Perfusion with Continuous Renal Replacement Therapy to Maintain Physiological Perfusate during Ex Vivo Organ Perfusion.

Background: The possibility of keeping liver grafts viable and functioning until transplantation has been explored since the 1950s. However, the current modalities of Normothermic Machine Perfusion (NMP) have shown several limitations, such as the inability to correct electrolytes and pH derangements efficiently. Combining NMP with continuous kidney replacement therapy (CKRT) might provide a promising new model to overcome these issues. Methods: An NMP that covers the organ perfusion, oxygenation, carbon dioxide removal, and thermal balance was connected to a CKRT circuit to ensure physiological hydro-electrolytes, acid-base balance, and catabolite removal from the perfusate. Results: The integration of NMP and CKRT maintains a neoplastic liver in a perfusion system with physiological perfusate for 100 h. CKRT re-established and maintained the hydro-electrolyte and acid-base status throughout the 100 h of perfusion. Significant limitations were the need for frequent monitoring of electrolytes and acid-base disorders and the loss of low molecular weight nutrients, which have to be replenished by manual infusion into the system. Conclusions: This novel CKRT-NMP integrated system may represent a practical and versatile model to support organs' perfusion and extend preservation times. Further experiments are needed to fix monitoring and adjusting processes.

The Impact of Gd-EOB-DTPA Contrast-enhanced MR Imaging on the Diagnosis of Benign Neoplastic and Non-neoplastic Liver Lesions

The Impact of Gd-EOB-DTPA Contrast-enhanced MR Imaging on the Diagnosis of Benign Neoplastic and Non-neoplastic Liver Lesions

Histopathological Spectrum and Molecular Characterization of Liver Tumors in the Setting of Fontan-Associated Liver Disease.

Univentricular heart is corrected with the Fontan procedure (FP). In the long term, so-called Fontan-associated liver diseases (FALDs) can develop. The aim of this study is to analyze the molecular profile of FALDs. FALDs between January 1990 and December 2022 were reviewed for histology and immunohistochemistry, laboratory data, and images. Targeted next generation sequencing (NGS), performed on the DNA and RNA of both neoplastic and non-lesional liver tissue, was applied. A total of 31/208 nodules > 1 cm in diameter were identified on imaging, but a liver biopsy was available for five patient demonstrating the following: one hepatocellular adenoma (HA), two hepatocellular carcinomas (HCCs), one fibrolamellar carcinoma (FLC), and one intrahepatic cholangiocarcinoma (ICC). Molecular analysis showed a copy number alteration involving FGFR3 in three cases (two HCCs and one ICC) as well as one HCC with a hotspot mutation on the CTNNB1 and NRAS genes. Tumor mutational burden ranged from low to intermediate. A variant of uncertain significance in GNAS was present in two HCCs and in one ICC. The same molecular profile was observed in a non-lesional liver. A DNAJB1-PRKACA fusion was detected only in one FLC. Neoplastic FALDs show some unusual molecular profiles compared with non-Fontan ones. The presence of the same alterations in non-lesional cardiac cirrhosis could contribute to the development of FALD.

Tissue factor pathway-related biomarkers in liver cancer: activated factor VII–antithrombin complex and tissue factor mRNA levels are associated with mortality

BackgroundTissue factor (TF), the main initiator of the coagulation cascade, plays a role in cancer progression and prognosis. Activated factor VII–antithrombin complex (FVIIa-AT) is considered an indirect marker of TF exposure by reflecting TF-FVIIa interaction. ObjectivesTo assess the link between FVIIa-AT plasma levels, TF messenger RNA (mRNA) expression, and survival in cancer. MethodsTF pathway–related coagulation biomarkers were assessed in 136 patients with cancer (52 with hepatocellular carcinoma, 41 with cholangiocarcinoma, and 43 with colon cancer) undergoing surgical intervention with curative intent. TF mRNA expression analysis in neoplastic vs nonneoplastic liver tissues was evaluated in a subgroup of 91 patients with primary liver cancer. ResultsFVIIa-AT levels were higher in patients with cancer than in 136 sex- and age-matched cancer-free controls. In patients with cancer, high levels of FVIIa-AT and total TF pathway inhibitor were associated with an increased mortality risk after adjustment for confounders, but only FVIIa-AT remained a predictor of mortality by including both FVIIa-AT and total TF pathway inhibitor in Cox regression (hazard ratio, 2.80; 95% CI, 1.23-6.39; the highest vs the lowest quartile). This association remained significant even after adjustment for extracellular vesicle–associated TF-dependent procoagulant activity. In the subgroup of patients with primary liver cancer, patients with high TF mRNA levels had an increased mortality risk compared with that for those with low TF mRNA levels (hazard ratio, 1.92; 95% CI, 1.03-3.57), and there was a consistent correlation among high FVIIa-AT levels, high TF mRNA levels, and increased risk of mortality. ConclusionHigh FVIIa-AT levels may allow the identification of patients with cancer involving high TF expression and predict a higher mortality risk in liver cancer.

Added value of 3D ultrasound image-guided hepatic interventions by X matrix technology

BackgroundImage-guided hepatic interventions are integral to the management of infective and neoplastic liver lesions. Over the past decades, 2D US was used for guidance of hepatic interventions; with the recent advances in US technology, 3D US was used to guide the hepatic interventions. This study aimed to illustrate the added value of 3D image-guided hepatic interventions by X matrix technology.MethodsThis prospective study was performed on 100 patients that were divided into two groups: group A which included 50 patients who were managed by using 2D US probe guidance, and group B which included 50 patients who were managed by using 3D X matrix US probe guidance. Thermal ablation was done for 70 patients; 40 radiofrequency ablation (RFA) (20 by the 2D probe and 20 by the 3D X matrix probe) and 30 microwave ablation (MWA) (15 by the 2D probe and 15 by the 3D X matrix probe). Chemical ablation (PEI) was done for 20 patients (ten by the 2D probe and ten by the 3D X matrix probe). Drainage of hepatic collections and biopsy from undiagnosed hepatic focal lesions were done for ten patients (five by the 2D probe and five by the 3D X matrix probe).ResultsThe efficacy of US-guided hepatic interventions by 3D X matrix probe was higher than the 2D probe but not significantly higher, with a p value of 0.705, 0.5428 for RFA and MWA, respectively, 0.5312 for PEI, and 0.2918 for drainage of hepatic collections and biopsy. The complications related to the use of the 3D X matrix probe were significantly lower than the 2D probe with a p value of 0.003. The timing of the procedure was shorter by the usage of a 3D X matrix probe in comparison with the 2D probe with a p value of 0.08, 0.34 for RFA and PEI and significantly shorter for MWA and drainage of hepatic collection, biopsy with a p value of 0.02, 0.001, respectively.Conclusions3D US-guided hepatic interventions by X matrix probe have better efficacy, less complication, and shorter time of procedure than the 2D US-guided hepatic interventions.

Follow-up of liver metastases: a comparison of deep learning and RECIST 1.1.

To compare liver metastases changes in CT assessed by radiologists using RECIST 1.1 and with aided simultaneous deep learning-based volumetric lesion changes analysis. A total of 86 abdominal CT studies from 43 patients (prior and current scans) of abdominal CT scans of patients with 1041 liver metastases (mean = 12.1, std = 11.9, range 1-49) were analyzed. Two radiologists performed readings of all pairs; conventional with RECIST 1.1 and with computer-aided assessment. For computer-aided reading, we used a novel simultaneous multi-channel 3D R2U-Net classifier trained and validated on other scans. The reference was established by having an expert radiologist validate the computed lesion detection and segmentation. The results were then verified and modified as needed by another independent radiologist. The primary outcome measure was the disease status assessment with the conventional and the computer-aided readings with respect to the reference. For conventional and computer-aided reading, there was a difference in disease status classification in 40 out of 86 (46.51%) and 10 out of 86 (27.9%) CT studies with respect to the reference, respectively. Computer-aided reading improved conventional reading in 30 CT studies by 34.5% for two readers (23.2% and 46.51%) with respect to the reference standard. The main reason for the difference between the two readings was lesion volume differences (p = 0.01). AI-based computer-aided analysis of liver metastases may improve the accuracy of the evaluation of neoplastic liver disease status. AI may aid radiologists to improve the accuracy of evaluating changes over time in metastasis of the liver. • Classification of liver metastasis changes improved significantly in one-third of the cases with an automatically generated comprehensive lesion and lesion changes report. • Simultaneous deep learning changes detection and volumetric assessment may improve the evaluation of liver metastases temporal changes potentially improving disease management.

A propensity score matched analysis of robotic and open hepatectomy for treatment of liver tumors. Clinical outcomes, oncological survival, and costs comparison.

Minimally invasive robotic hepatectomy is gaining popularity with a faster rate of adoption when compared to laparoscopic approach. Technical advantages brought by the robotic surgical system facilitate a transition from open to minimally invasive technique in hepatic surgery. Published matched data examining the results of robotic hepatectomy using the open approach as a benchmark are still limited. We aimed to compare the clinical outcomes, survival, and costs between robotic and open hepatectomy undertaken in our tertiary hepatobiliary center. With IRB approval, we prospectively followed 285 consecutive patients undergoing hepatectomy for neoplastic liver diseases between 2012 and 2020. Propensity score matched comparison of robotic and open hepatectomy was conducted by 1:1 ratio. Data are presented as median (mean ± SD). The matching process assigned 49 patients to each arm, open and robotic hepatectomy. There were no differences in R1 resection rates (4% vs 4%; p = 1.00). Differences in perioperative variables between open and robotic hepatectomy included postoperative complications (16% vs 2%; p = 0.02) and length of stay (LOS) [6 (7 ± 5.0) vs 4 (5 ± 4.0) days; p = 0.002]. There were no differences between open and robotic hepatectomy regarding postoperative hepatic insufficiency (10% vs 2%; p = 0.20). No difference was seen in long-term survival outcomes. While there were no differences in costs, robotic hepatectomy was associated with lower reimbursement [$20,432 (39,191 ± 41,467.81) vs $33,190 (67,860 ± 87,707.81); p = 0.04] and lower contribution margin [$-11,229 (3902 ± 42,572.43) vs $8768 (34,690 ± 89,759.56); p = 0.03]. Compared to open approach, robotic hepatectomy robotic offers lower rates of postoperative complications, shorter LOS and similar costs, while not compromising long-term oncological outcomes. Robotic hepatectomy may eventually become the preferred approach in minimally invasive treatment of liver tumors.

Phosphorothioated amino-AS1411 aptamer functionalized stealth nanoliposome accelerates bio-therapeutic threshold of apigenin in neoplastic rat liver: a mechanistic approach

Hepatocellular carcinoma (HCC) is a leading cause of death globally. Even though the progressive invention of some very potent therapeutics has been seen, the success is limited due to the chemotherapeutic resistance and recurrence in HCC. Advanced targeted treatment options like immunotherapy, molecular therapy or surface-engineered nanotherapeutics could offer the benefits here owing to drug resistance over tumor heterogenicity. We have developed tumor-sensing phosphorothioate and amino-modified aptamer (AS1411)-conjugated stealth nanoliposomes, encapsulating with apigenin for precise and significant biodistribution of apigenin into the target tumor to exploit maximum bio-therapeutic assistances. The stable aptamer functionalized PEGylated nanoliposomes (Apt-NLCs) had an average vesicle size of 100–150 nm, a smooth surface, and an intact lamellarity, as ensured by DLS, FESEM, AFM, and Cryo-TEM. This study has specified in vitro process of optimum drug (apigenin) extrusion into the cancer cells by nucleolin receptor-mediated cellular internalization when delivered through modified AS1411 functionalized PEGylated nanoliposomes and ensured irreversible DNA damage in HCC. Significant improvement in cancer cell apoptosis in animal models, due to reduced clearance and higher intratumor drug accumulation along with almost nominal toxic effect in liver, strongly supports the therapeutic potential of aptamer-conjugated PEGylated nanoliposomes compared to the nonconjugated formulations in HCC. The study has established a robust superiority of modified AS1411 functionalized PEGylated nanoliposomes as an alternative drug delivery approach with momentous reduction of HCC tumor incidences.Graphical

Survey of liver pathologists to assess attitudes towards digital pathology and artificial intelligence

AimsA survey of members of the UK Liver Pathology Group (UKLPG) was conducted, comprising consultant histopathologists from across the UK who report liver specimens and participate in the UK National...

Focal Nodular Hyperplasia-Like Lesions With Glypican-3 Positivity in Infancy.

Glypican-3 is often used to discriminate between neoplastic and nonneoplastic liver. In focal lesions, positivity may be considered suggestive of a malignancy such as hepatoblastoma. However, glypican-3 is also normally expressed in the immature liver. We present a series of 5 cases of focal nodular hyperplasia (FNH)-like lesions arising in very young patients with glypican-3 expression and highlight the challenges these lesions present in the differential diagnosis of hepatoblastoma. Cases were obtained from the files of 3 tertiary pediatric hospitals. Clinical data were obtained from the electronic medical record and histopathologic material including immunohistochemical stains were reviewed. Patients were aged 2 weeks to 6 months with peak AFP levels ranging from 88.6 to 204,696 ng/mL. Microscopically, all were variably demarcated hepatocellular lesions with cords of hepatocytes, marked sinusoidal dilatation, and occasional fibrous bands and areas reminiscent of central scar with bile ducts. No significant cytologic atypia or increased mitotic activity were present. All showed glypican-3 expression and were negative for nuclear beta-catenin with intact reticulin framework. Our study highlights the pitfalls of evaluating focal liver lesions in infants when high AFP levels and glypican-3 expression may reflect immaturity rather than neoplasia.

Hepatectomy-induced apoptotic extracellular vesicles stimulate neutrophils to secrete regenerative growth factors.

Surgical resection of the cancerous tissue represents one of the few curative treatment options for neoplastic liver disease. Such partial hepatectomy (PHx) induces hepatocyte hyperplasia, which restores liver function. PHx is associated with bacterial translocation, leading to an immediate immune response involving neutrophils and macrophages, which are indispensable for the priming phase of liver regeneration. Additionally, PHx induces longer-lasting intrahepatic apoptosis. Herein, we investigated the effect of apoptotic extracellular vesicles (aEVs) on neutrophil function and their role in this later phase of liver regeneration. A total of 124 patients undergoing PHx were included in this study. Blood levels of the apoptosis marker caspase-cleaved cytokeratin-18 (M30) and circulating aEVs were analyzed preoperatively and on the first and fifth postoperative days. Additionally, the invitro effects of aEVs on the secretome, phenotype and functions of neutrophils were investigated. Circulating aEVs increased at the first postoperative day and were associated with higher concentrations of M30, which was only observed in patients with complete liver recovery. Efferocytosis of aEVs by neutrophils induced an activated phenotype (CD11bhighCD16highCD66bhighCD62Llow); however, classical inflammatory responses such as NETosis, respiratory burst, degranulation, or secretion of pro-inflammatory cytokines were not observed. Instead, efferocytosing neutrophils released various growth factors including fibroblast growth factor-2 and hepatocyte growth factor (HGF). Accordingly, we observed an increase of HGF-positive neutrophils after PHx and a correlation of plasma HGF with M30 levels. These data suggest that the clearance of PHx-induced aEVs leads to a population of non-inflammatory but regenerative neutrophils, which may support human liver regeneration. In this study, we show that the surgical removal of a diseased part of the liver triggers a specific type of programmed cell death in the residual liver tissue. This results in the release of vesicles from dying cells into the blood, where they are cleared by circulating immune cells. These respond by secreting hepatocyte growth factors that could potentially support the regeneration of the liver remnant.

Hepatic benign and malignant masses in children: a single UK tertiary centre experience.

The aim of this study was to review the incidence, spectrum and investigation of liver masses presenting to our tertiary liver unit. A retrospective single-centre cohort study of paediatric patients (age < 16years) diagnosed with a liver mass who were investigated at a UK paediatric hepatobiliary tertiary referral centre. Data relating to the clinical findings at presentation, source of referral, diagnostic investigations and histopathology findings were recorded and analysed. 107 patients were identified between July 2012 and July 2019 (55 females). 69 (64%) patients had benign liver lesions, whereas the remaining 38 (36%) were found to have malignant masses. The liver lesions were most commonly detected incidentally (33%) with the second most common presentation being with palpable mass(29%). 82 (77%) patients were referred from other hospitals. All patients underwent USS, 74% MRI, 36% CT, 5% CEUS, 1% PET and 5% HIDA scan with 47% ultimately undergoing biopsy. 72% of patients had AFP measured. The most common benign liver masses were haemangioma 33 (48%), hepatic cyst 17 (25%) and FNH 12 (19%). Amongst the malignant lesions, 29 (76%) were hepatoblastoma and 3 (8%) were hepatocellular carcinoma. This large review series demonstrates that just over 1/3 of patients presenting to a paediatric tertiary referral centre with a focal liver lesion had neoplastic liver lesions, despite the published literature commonly stating that 2/3 of paediatric liver masses are malignant.

Expression of connexins and pannexins in diseased human liver.

Connexin proteins can form hexameric hemichannels and gap junctions that mediate paracrine and direct intercellular communication, respectively. Gap junction activity is crucial for the maintenance of hepatic homeostasis, while connexin hemichannels become particularly active in liver disease, such as hepatitis, fibrosis, cholestasis or even hepatocellular carcinoma. Channels consisting of connexin-like proteins named pannexins have been directly linked to liver inflammation and cell death. The goal of the present study was to characterize the expression and subcellular localization of connexins and pannexins in liver of patients suffering from various chronic and neoplastic liver diseases. Specifically, real-time quantitative reverse transcription polymerase chain reaction, immunoblotting and immunohistochemistry analyses were performed on human liver biopsies. It was found that pannexin1 and pannexin2 gene expression are correlated to a certain degree, as is pannexin1 protein expression with connexin32 and connexin43 protein expression. Furthermore, this study is the first to detect pannexin3 in human patient liver biopsies via both immunoblot and immunohistochemistry.

Hepatitis Activity Index and its Clinical and Biochemical Parameters in Liver Diseases- A Retrospective Study

Introduction: Hepatitis Activity Index (HAI) is a scoring system devised by Ishak K et al., for grading and staging chronic hepatitis. The HAI provides a numerical score that is both objective and reproducible, it may be useful as either an alternative or supplement to the use of conventional pathological terminology in the study and management of chronic hepatitis patients. Aim: To assess the efficiency of HAI scoring in the non neoplastic liver diseases by relating it with the clinical and biochemical parameters. Materials and Methods: This retrospective study was conducted in the Department of Pathology at Sri Ramachandra Medical College and Research Institute, Chennai, Tamil Nadu, India, from 2010 to 2015. A total of 57 (58%) neoplastic cases and 41 (42%) non neoplastic cases were retrieved. The data was reassessed, HAI score and grade was noted and compared with the clinical and biochemical parameters. Chronic liver disease was classified as chronic viral hepatitis {Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV)} or cirrhosis. Alkaline phosphatase levels, Serum Glutamic Oxaloacetic Transaminase (SGOT) levels , Serum Glutamic Pyruvic Transaminase (SGPT) levels were analysed. Descriptive analysis was done and the data was represented as frequency and percentage in Microsoft Excel. Results: Among the non neoplastic cases, 21 (51%) belonged to hepatitis and cirrhosis and 20 (49%) belonged to others. In patients with high alkaline phosphatase levels, the predominant HAI score was 4. In cases with high SGOT levels, the predominant HAI score was 5 and 6. In cases with high SGPT levels, the HAI score was 5,6, and 7. Conclusion: The HAI is useful in assessing the extent of active inflammation. It gives an objective guideline to the treating physician. The HAI score in combination with clinical and biochemical parameters offers a better insight into disease severity.

Genetic Variability in Patients with HCV-Related Hepatocellular Carcinoma.

BackgroundThe present paper evaluates the genetic variability of HCV in patients with hepatocellular carcinoma (HCC).MethodsAmino acid substitutions (aas) in NS3, NS5A and core regions were analyzed in 17 patients with HCC (Cases) and 13 without HCC (Controls), all naïve to DAAs. For the Cases, a sample of neoplastic liver tissue, non-neoplastic liver tissue and a serum sample were collected; for the Controls, a sample of liver tissue was collected. Sanger sequencing of three regions was performed using homemade protocols.ResultsPhylogenetic trees showed that there was no difference in the virus populations in the three compartments analyzed for the three HCV regions in patients with HCC. Low variability and no difference between the Cases and Controls were observed in the core and NS5A regions; however, in the NS3 region, a higher variability was observed in the Cases. No difference was observed in the core region between Cases and Controls. In NS3, aa substitutions at positions 103 and 122 were more frequently found in Cases than Controls (in both cases 50% vs 9.1%, p<0.05); moreover, aas in positions 32, 44 (p=0.035 for both), 79 (p=0.008) and 121 (p=0.018) were observed in the Cases and absent in the Controls. Finally, considering the NS5A region, aa substitutions at positions 37 and 54 were more frequently identified in the Cases than the Controls, but without statistical significance.ConclusionThese data may suggest a higher aa variability in patients with HCC than in those without, especially in the NS3 region.

Hepatic tuberculosis masquerading as malignancy.

Hepatic tuberculosis (HTB) is rare and mimics neoplastic liver lesions clinico-radiologically leading to misdiagnosis and even unnecessary surgery. We analysed 43 cases of HTB diagnosed at a referral cancer centre over 10years. Clinical details, investigations and treatment received were noted. The median age was 46years with a female preponderance (58%). HTB was diagnosed incidentally in 28% cases during surveillance imaging for a previous cancer. Constitutional symptoms (31, 72%), abdominal pain (25, 58%), fever (12, 28%), hepatomegaly (22, 51%), elevated alkaline phosphatase (34, 79%), elevated aminotransferases (18, 42%) and hypoalbuminemia (19, 45%) were common features. All cases had negative HIV serology and normal tumor markers. Twenty-two (52.5%) had solitary liver lesion and lesions > 2cm in 28 (65%). Ultrasound showed hypoechoic lesions in 31 of 33 cases. Computed tomography showed hypodense lesions (43,100%) with mild peripheral enhancement (32, 74%). Calcifications (5, 12%) and capsular retraction (8, 19%) was uncommon. MRI was performed in seven cases commonly showed T1 hypointense, T2 hyperintense lesions with restricted diffusion. Histopathology showed granulomatous inflammation (42, 97.5%), Langhan's giant cells (41, 95%) and caseation necrosis (35, 85%). Acid-fast stain and PCR positivity was uncommon. Extrahepatic organs were involved in 20 (46.5%). HTB mimicked cholangiocarcinoma (25, 58%), liver metastasis (11, 26%) and lymphoma (3, 7%). Six patients underwent liver resection with a presumptive diagnosis of cancer without a preoperative biopsy. All patients received antitubercular therapy, 37 had clinico-radiological response, there were 3 deaths and 3 patients were lost to follow-up. HTB is rare and can mimic a malignancy clinico-radiologically. Calcifications and pseudocapsule appearance on multiphase CT scan may help in differentiating HTB from hepatic malignancy. Tumor markers are normal while histopathology is generally diagnostic. A high index of suspicion is required to avoid unnecessary surgery as the patients respond well to ATT. This is aretrospective and observational study hence clinical trial registration is not applicable.

DNA methylation mediated downregulation of histone H3 variant H3.3 affects cell proliferation contributing to the development of HCC

Chromatin alterations brought by histone variants and modifications potentially regulate gene transcription from tumor initiation to progression. Histone H3.3 variant is one such epigenetic player important for disease progression and development. Though many studies have implicated H3.3 role in cancer progression and metastasis, its regulation, importance of specific modifications and chaperones have been not understood yet. We report DNA methylation mediated downregulation of histone H3 variant H3.3 in HCC and a concomitant increase in the level of the H3.2 variant. The loss of H3.3 in cancer tissues correlates with a decrease in the histone modifications associated with active transcription like H3K9/K14/K27Ac and H3K4Me3. The ectopic overexpression of H3.3 and H3.2 did not affect global PTMs and cell physiology, probably owing to the deregulation of specific histone chaperones CAF-1 (for H3.2) and HIRA (for H3.3) as observed in HCC tissues. Notably, knockdown of P150, a subunit of CAF-1 leads to a cell cycle arrest in S-phase in a neoplastic rat liver cell line, possibly due to the decrease in the histone levels necessary for DNA packaging. Remarkably, modulation of H3.3 in pre-neoplastic rat liver cells lead to an increase in cell proliferation and a decreased transcription of tumor suppressor genes, recapitulating the tumor cell phenotype. Our data suggests, inhibition of DNA methylation and histone deacetylation leads to the restoration of histone H3 variant expression in tumor cells.

Comparison of fine-needle cytologic diagnosis between the left and right liver lobes of dogs and cats with diffuse liver disease.

Background and Aim:Ultrasound-guided fine-needle sample collection for cytology with manual restraint is frequently used for the primary assessment of diffuse liver disease in veterinary patients in Thailand. For better diagnosis, repeated collection of samples ensures the collection of adequate, representative samples, which increase diagnostic accuracy. However, in those that are unable to receive general anesthesia, it is difficult to collect the samples from several liver locations in manually restrained dogs and cats. The study aimed to compare the cytologic diagnosis of the ultrasound-guided fine-needle non-aspiration technique between the left and right liver lobes in dogs and cats with neoplastic and non-neoplastic diffuse liver disease.Materials and Methods:This prospective study included 25 client-owned dogs and cats with diffuse liver diseases. Two liver samples were randomly collected from the left and right liver lobes under ultrasound guidance for cytologic examination. All slides were subsequently examined blindly by experienced pathologists for cytologic analysis with cytologic agreement scores (CASs).Results:Among all 50 samples obtained from ultrasound-guided fine-needle sample collection of the left and right liver, 78% were diagnostic and 22% were non-diagnostic. In the diagnostic group, 73.3% of fine-needle samples had concordant results between the left and right liver, which exhibited 100% cytologic agreement in lymphoma and 63.6% in non-neoplastic groups. Samples collected from the left liver had slightly higher CAS and higher cytologic quality than had those from the right liver lobe (p=0.053).Conclusion:The location and number of sample collections did not have a significant difference in the cytologic diagnosis of diffuse liver disease, especially in patients with lymphoma. For manually restrained patients, one time ultrasound-guided non-aspiration cytology procedure from the left liver lobe not only decreased restraint duration and minimized tissue trauma but also allowed for an adequate cytologic diagnosis in diffuse liver disease compared to multiple collections.

C - REACTIVE PROTEIN AND ITS ASSOCIATION WITH SERUM URIC ACID AND BICARBONATE LEVEL IN COPD

AIM: The study was planned to evaluate the association of C - reactive protein with Serum Uric Acid and Bicarbonate Level in COPD. MATERIAL AND METHODS: In the present study total 100 (n=100) patients diagnosed for COPD, were enrolled for the study. Patients with neoplastic pathologies, pneumonia and Liver or renal diseases, pregnant and lactating females were excluded from the study. RESULT: The mean level of Serum Bicarbonate, C-reactive protein and uric acid were signicantly higher in COPD patients. A signicant association was observed (p ≤ 0.0001). CONCLUSION: In the present study higher bicarbonate levels that could be the individual biomarker which can assess the respiratory acidosis and CRP and Uric Acid levels judges the severity the disease.

Detecting Imaging For Neoplastic Liver Masses in Hepatic Patients Who Received Direct Acting Antiviral Drugs

Background: Hepatocellular carcinoma makes up 75%-85% of all primary liver cancers and is the fourth most common cause of cancer related death worldwide. The aim of this study was to screen for hepatocellular carcinoma in hepatic patients who received direct acting antiviral drugs using different imaging modalities. Methods: This was a cross sectional study included 50 patients who were hepatic and received Direct Acting Antiviral '' DAA'' and were carried out at radiology department in Elobour Hospital for Health Insurance after obtaining written informed consent from all patients. Results: There were 31(62%) male, 19(38%) female, the mean age 52.28 years old with range (39-65), 35(70%) urban, 15(30%) rural. There were (70%) with duration of illness ≤ 5 years, (30%) with > 5 years, (100%) with DAA, (90%) easy to treat, (10%) difficult to treat. There were 35(70%) with average liver, 14(28%) with shrunken liver, 1(2%) with enlarged liver, 13(26%) with Bright pattern, 34(68%) with cirrhotic, 3(6%) with coarse bright, the mean P.V diameter 14.68(± 2.51 SD) with range (9-17).There were (100%) with Single focal lesion in RT lobe, the mean size 4.47with range (3.6-5.6), (33.3%) Isochoric, (33.3%) with Hypo echoic, (33.3%) with Hyper echoic, (66.7%) with malignancy. There were 3(100%) with typical CT enhancement, 1(33.3%) with P.V thrombosis. There was no one with Affection on liver vascular, no one with intrahepatic biliary radicles, no one with L.N in porta hepatis. Conclusion: Based on our findings, we recommend for close imaging evaluations after DAA in cirrhotic patients.