Resection Of Liver Tissue Research Articles

A Hepatocellular Cancer Patient-derived Organoid Xenograft Model to Investigate Impact of Liver Regeneration on Tumor Growth.

Recurrence poses a notable challenge after hepatocellular carcinoma (HCC) treatment, impacting more than 70% of patients who undergo surgical resection. Recurrence stems from undetected micro-metastasis or de novo cancer, potentially triggered by postsurgical liver regeneration. Prior research employed HCC cell lines in orthotopic models to study the impact of liver regeneration, but their limited validity prompted the need for a more representative model. Here, we introduce a novel approach utilizing patient-derived HCC organoids to investigate the influence of liver regeneration on HCC. Patient tumor tissues are processed to create tumor organoids, embedded in a three-dimensional basement membrane matrix, and cultured in a liver-specific medium. One million organoids are injected into the right superior lobe (RSL) of immunodeficient mice, confirming macroscopic tumor growth through sonography. The intervention group undergoes resection of the left lateral lobe (LLL) (30% of total liver volume) or additionally, the middle lobe (ML) (65% of total liver volume) to induce liver regeneration within the tumor site. The control group experiences re-laparotomy without liver tissue resection. After 2 weeks, both groups undergo tumor and normal tissue explantation. In conclusion, this patient-derived HCC organoid model offers a robust platform to investigate the impact of liver regeneration post-cancer resection. Its multi-cellular composition, genetic diversity, and prolonged culture capabilities make it an invaluable tool for studying HCC recurrence mechanisms and potential interventions.

ИЗМЕНЕНИЯ СЫВОРОТОЧНЫХ КОНЦЕНТРАЦИЙ ПРЯМЫХ БИОМАРКЕРОВ ФИБРОЗИРОВАНИЯ ПРИ ХРОНИЧЕСКИХ БОЛЕЗНЯХ ПЕЧЕНИ У ДЕТЕЙ

It is assumed that serum concentrations of type I, III, IV collagen (Col I, Col III, Col IV) and hyaluronic acid (HA) can provide informative evidence for the diagnosis of liver fibrosis (LF) using non-invasive procedures, however, there is insufficient data on the subject in paediatrics. Objectives: to study characteristics of changes in concentrations of Col I, Col III, Col IV and HA in blood serum in accordance with the stages of liver fibrosis in children. Materials and methods of research: a prospective study was carried out, which included 80 patients aged 5 to 17 years with chronic liver diseases of various etiologies, who underwent marginal resection of liver tissue under laparoscopic control, then a morphological study of the obtained biopsy was performed with determination of the stage of fibrosis on the METAVIR scale and the content of Col I, Col III, Col IV and HA in blood serum by the method of enzyme immunoassay. Results: the assessment of the content of K-I in the blood serum allows differentiating the stage F1 and F3 from F4 (p=0,025, p=0,006), Col IV – F1 from F2 (p=0,011), F3 (p=0,002) and F4 (p<0,001), HA – F1 from F3 (p=0,041), and also F4 from F1 (p<0,001), F2 (p<0,001) and F3 (p<0,001). There were no statistically significant differences in the content of Col III at different stages of LF (p=0,061). Statistically significant correlations of the histological stage of LF with changes in serological levels of Col I (ρ=–0,267, p=0,023), Col IV (ρ=0,409, p<0,001), and HA (ρ=0,575, p<0,001), and also the relationship between the concentrations of Col IV and HA (ρ=0,265, p=0,023). Conclusions: the correlations found in the histological phase of LF with changes in serological levels of Col I, Col IV and HA lead to the conclusion that fibrosis direct biomarkers are of diagnostic importance in determining the stage of LF, which is of great importance for practical medicine, especially in pediatrics.

The informative value of assessment of direct serum biomarkers for diagnosis of various stages of liver
 fibrosis in children

Introduction. Serum concentrations of collagens I, III, IV types (K-I, K-III, K-IV) and hyaluronic acid (HA) are reported to be informative in terms of noninvasive diagnosis liver fibrosis stages. In pediatrics, there is not enough data on this. Purpose was to assess the diagnostic value of direct biomarkers in predicting the stage of fibrosis in children with chronic liver diseases (CLD). Materials and methods. A prospective single-center study included 80 children with CLD . All patients underwent marginal resection of liver tissue under laparoscopic control. The serum K-I, K-IV, and HA concentration were measured by enzyme immunoassay. The authors applied ROC curve analysis to assess quantitative signs’ diagnostic significance in predicting a specific outcome. Results.The optimal KI value for the diagnosis of cirrhosis was 144.24 ng/ml, with AUROC: 0.758 ± 0.101 with 95% CI: 0.560-0.957, sensitivity and specificity 65.2% and 77.8%, respectively. The optimal K-IV values for the diagnosis of moderate fibrosis and cirrhosis were 11.29 ng/ml and 27.40 ng/ml, respectively, with AUROC 0.807 ± 0.092 with 95% CI: 0.627-0.987, 0.685 ± 0.062 with 95% CI: 0.567-0.810, sensitivity 82.4% and 61.15%, specificity 66.7%, and 64.7%, respectively. The optimal BG values for the diagnosis of weak and moderate fibrosis were 34.9 ng/ml and 36.5 ng/ml, for cirrhosis 38.3 ng/ml, with AUROC 0.912 ± 0.050 with 95% CI: 0.815-1.00; 0.849 ± 0.064 with 95% CI: 0.723-0.974, and 0.825 ± 0.048 with 95% CI: 0.730-0.920, respectively. Sensitivity was 84.6% at all stages, specificity - 77.8%, 61.5% and 70.6%, respectively. Conclusions. LF biomarkers have diagnostic significance in the detection of the stages of liver fibrosis. LF biomarkers are informative, reproducible noninvasive indices in the diagnosis of liver fibrosis in children.

Autoradiography and biopsy measurements of a resected hepatocellular carcinoma treated with 90 yttrium radioembolization demonstrate large absorbed dose heterogeneities

PurposeRadioembolization is an alternative palliative treatment for hepatocellular carcinoma. Here, we examine the uptake differences between tumor tissue phenotypes and present a cross-section of the absorbed dose throughout a liver tissue specimen. Methods and materialsA patient with hepatocellular carcinoma was treated with 90Y radioembolization followed by liver tissue resection. Gamma camera images and autoradiographs were collected and biopsy tissue samples were analyzed using a gamma well counter and light microscopy. ResultsAn analysis of 25 punched biopsy tissue samples identified 4 tissue regions: Normal tissue, viable tumor tissue with and without infarcted areas, and tumor areas with postnecrotic scar tissue. Autoradiography and biopsy tissue sample measurements showed large dose differences between viable and postnecrotic tumor tissue (159 Gy vs 23 Gy). ConclusionsRadioembolization of 90 yttrium with resin microspheres produces heterogeneous-absorbed dose distributions in the treatment of unifocal hepatic malignancies that could not be accurately determined with current gamma camera imaging techniques.

New mechanisms involving the EGFR and FGF15/19 systems in liver regeneration and carcinogenesis

New mechanisms involving the EGFR and FGF15/19 systems in liver regeneration and carcinogenesis

2151 ORAL Tissue Composition Estimated With an Interventional Fiber Optic Probe During Liver Tissue Resection

2151 ORAL Tissue Composition Estimated With an Interventional Fiber Optic Probe During Liver Tissue Resection

Model construction for reperfusion of the isolated pig liver

In recent years thermal ablation of liver tumors as a minimally invasive method became a promising alternative to conventional strategies such as chemotherapy or resection of liver tissue. Thereby an electrode is placed inside the tumor delivering energy in the form of high frequency current into the target volume to achieve and maintain a tissue temperature between 60 and 100 degrees C. Cells exposed to this thermic stress undergo coagulation necrosis and are irreversibly damaged. To protect vital liver structures from heat, it is necessary to develop an online temperature monitoring system. An experimental setup perfusing isolated pig livers under physiological conditions with 0.9% NaCl solution was established to develop and evaluate the measuring technique.

Surgery for Metachronous Solitary Liver Metastases of Renal Cell Carcinoma

Purpose The postoperative outcome and survival of patients undergoing surgery for metachronous solitary liver metastases of renal cell carcinoma were evaluated. Materials and Methods Between 1983 and 1993, 17 patients with metachronous liver metastases of renal cell carcinoma underwent laparotomy for metastatic liver disease. All patients had undergone radical nephrectomy a mean of 3.6 years before the diagnosis of liver metastases. Results Surgical resection was feasible in 13 of 17 patients with right hemihepatectomy in 9 (3 multivisceral resections), wedge resection in 4 and ex situ (mobilization and eversion out of the abdomen) resection in 1. Stage RO resection (complete removal, negative surgical margins with no macroscopic disease left behind) was possible in 11 of 13 cases (85%). In patients with metastatic liver tissue resection the mortality rate was 31% (4 of 13) with additional significant morbidity in another 2. Mean survival of patients with nonresectable disease was 4 months, which increased to 16 months after resection. Conclusions Complete resection of metachronous liver metastases can be achieved in the majority of patients. However, significant morbidity and mortality as well as the limited prognosis even after RO resection strongly suggest careful patient selection.

Initiation of liver growth by tumor necrosis factor: deficient liver regeneration in mice lacking type I tumor necrosis factor receptor.

The mechanisms that initiate liver regeneration after resection of liver tissue are not known. To determine whether cytokines are involved in the initiation of liver growth, we studied the regeneration of the liver after partial hepatectomy (PH) in mice lacking type I tumor necrosis factor receptor (TNFR-I). DNA synthesis after PH was severely impaired in these animals, and the expected increases in the binding of the NF-kappaB and STAT3 transcription factors shortly after PH failed to occur. Binding of AP-1 after PH was decreased in TNFR-I knockout mice compared with animals with the intact receptor whereas C/EBP binding was not modified. Injection of interleukin 6 in TNFR-I-deficient animals 30 min before PH corrected the defect in DNA synthesis and restored STAT3 and AP-1 binding to normal levels but had no effect on NF-kappaB binding in the regenerating liver. The results indicate that TNF, signaling through the TNFR-I, can initiate liver regeneration and acts by activating an interleukin 6-dependent pathway that involves the STAT3 transcription factor.

Gallbladder carcinoma first diagnosed at microscopic examination of gallbladders removed for presumed benign disease.

The patients who survive gallbladder carcinomas more than five years are usually those in whom the carcinoma was first diagnosed at microscopic examination of gallbladders removed for presumed benign disease. A group of 32 such patients (from a series of 120 cases) was studied. The prognosis was very bad (longest survival 2.5 years) in 21 of the patients where the cancer involved all the layers of the gallbladder wall. The prognosis was far better in the 11 patients in which the cancer was confined to the mucosa or submucosa. Sixty-four per cent of the patients were alive after 5 years and 44% after 10 years. Five of the 11 patients died because of recurrence. Simple cholecystectomy had been performed in all the patients except one who underwent a right hepatic lobectomy. Radical cholecystectomy including a wedge resection of liver tissue and dissection of the regional lymph nodes is recommended in all patients with inapparent gallbladder carcinomas.