Benign liver tumors in pediatric patients-Review with emphasis on imaging features

Benign hepatic tumors are commonly observed in adults,but rarely reported in children.The reasons for this remain speculative and the exact data concerning the incidence of these lesions are lacking.Benign hepatic tumors represent a diverse group of epithelial and mesenchymal tumors.In pediatric patients,most benign focal liver lesions are inborn and may grow like the rest of the body.Knowledge of pediatric liver diseases and their imaging appearances is essential in order to make an appropriate differential diagnosis.Selection of the appropriate imaging test is challenging,since it depends on a number of age-related factors.This paper will discuss the most frequently encountered benign liver tumors in children(infantile hepatic hemangioendothelioma,mesenchymal hamartoma,focal nodular hyperplasia,nodular regenerative hyperplasia,and hepatocellular adenoma),as well as a comparison to the current knowledge regarding such tumors in adult patients.The current emphasis is on imaging features,which are helpful not only for the initial diagnosis,but also for pre- and posttreatment evaluation and follow-up.In addition,future perspectives of contrast-enhanced ultrasound(CEUS) in pediatric patients are highlighted,with descriptions of enhancement patterns for each lesion being discussed.The role of advanced imaging tests such as CEUS and magnetic resonance imaging,which allow for non-invasive assessment of liver tumors,is of utmost importance in pediatric patients,especially when repeated imaging tests are needed and radiation exposure should be avoided.

DNA methylation in hepatocellular carcinoma

As for many other tumors,development of hepatocellular carcinoma(HCC)must be understood as a multistep process with accumulation of genetic and epigenetic alterations in regulatory genes,leading to activation of oncogenes and inactivation or loss of tumor suppressor genes(TSG).In the last decades,in addition to genetic alterations,epigenetic inactivation of(tumor suppressor) genes by promoter hypermet hylation has been recognized as an important and alternative mechanism in tumorigenesis.In HCC,aberrant methylation of promoter sequences occurs not only in advanced tumors, it has been also observed in premalignant conditions just as chronic viral hepatitis B or C and cirrhotic liver. This review discusses the epigenetic alterations in hepatocellular carcinoma focusing DNA methylation.

Expression of c-kit receptor in human cholangiocarcinoma and in vivo treatment with imatinib mesilate in chimeric mice

AIM： To investigate the c-kit expression in biliary tract cancer cell lines and histological sections from patients with extrahepatic cholangiocarcinoma （CC） and to evaluate the efficacy of in vitro and in vitro treatment with imatinib mesilate. METHODS： The protein expression of c-kit in the human biliary tract cancer cell lines Mz-ChA-2 and EGI-1 and histological sections from 19 patients with extrahepatic CC was assessed by immunoblotting, immunocytochemistry, and immunohistochemistry. The anti-proliferative effect of imatinib mesilate on biliary tract cancer cell lines Mz-ChA-2 and EGI-1 was studied in vitro by automated cell counting. In addition, immunodeficient NMRI mice （Taconic^TM） were subcutaneously injected with 5 × 10^6 cells of cell lines MzChA-2 and EGI-1. After having reached a tumour volume of 200 mm^3, daily treatment was started intraperitoneally with imatinib mesilate at a dose of 50 mgikg or normal saline （NS）. Tumor volume was calculated with a Vernier caliper. After 14 d, mice were sacrificed with tumors excised and tumor mass determined.RESULTS： Immunoblotting revealed presence of c-kit in Mz-ChA-2 and absence in EGI-1 cells. Immunocytochemistry with c-kit antibodies displayed a cytoplasmatic and membraneous localization of receptor protein in Mz-ChA-2 cells and absence of c-kit in EGI-1 cells, c-kit was expressed in 7 of 19 （37%） extrahepatic humanCC tissue samples, 2 showed a moderate and 5 a rather weak immunostaining. Imatinib mesilate at a low concentration of 5 μmoliL caused a significant growth inhibition in the c-kit positive cell line Mz-ChA-2 （31%）, but not in the c-kit negative cell line EGI-1 （0%） （P〈0.05）. Imatinib mesilate at an intermediate concentration of 10 μmoliL inhibited cellular growth of both cell lines （51% vs 57%）. Imatinib mesilate at a higher concentration of 20 μmoliL seemed to have a general toxic effect on both cell lines. The IC50 values were 9.7 μmoliL and 11 μmoliL, respectively. After 14 d of in vitro treatment with imatinib mesilate, using the chimeric mouse model, c-kit positive Mz-ChA-2 tumors had a significantly reduced volume and mass as compared to NS treatment （P〈 0.05）. In contrast to that, treatment of mice bearing c-kit negative EGI-1 tumors did not result in any change of tumor volume and mass as compared to NS treatment. CONCLUSION： c-kit expression is detectable at a moderate to low protein level in biliary tract cancer. Imatinib mesilate exerts marked effects on tumor growth in vitro andin vitro dependent on the level of c-kit expression.

Expression of toxin-related human mono-ADP-ribosyltransferase 3 in human testes

Aim： To investigate wether the corresponding protein of mono-ADP-ribosyltransferase 3 （ART3） mRNA is expressed in human testes and, if so, whether the expression is cell type-specific. Methods： ART3 mRNA was determined in human testes and sperm by reverse transcription-polymerase chain reaction （RT-PCR）. The glycosylphosphatidylinositol linkage of ART3 was shown by treating ART3-transfected HEK-293-T cells with phospholipase C. Fluorescent activated cell sorter （FACS）-analyses were used to detect ART3 on mature spermatozoa and immunohistological studies to detect the protein in testes. Results： ART3 protein was shown to be present in testes. It was found on spermatocytes only. It was absent from spermatogonia, spermatids and spermatozoa. The absence of ART3 from spermatozoa was confirmed by FACS-analysis. ART3 protein was detected neither within a seminoma nor on Leydig cells. Conclusion： Here we show for the first time that ART3 protein is expressed in testes in particular on spermatocytes, indicating that ART3 exerts a specific function only required at a particular stage of spermatogenesis.

Triggers of histologically suspected drug-induced colitis

BACKGROUND Drug toxicity is a common and even serious problem in the gastrointestinal tract that is thought to be caused by a broad spectrum of agents.Although withdrawal of the causative agent would cure the disease knowledge is scarce and mostly derives from case reports and series.AIM To investigate potential triggers of drug-induced colitis(DiC).METHODS We conducted a retrospective,observational case control study.Patients were assigned to DiC or one of two age-and gender-matched control groups(noninflammatory controls and inflammatory colitis of another cause)based on histopathological findings.Histopathology was reassessed in a subset of patients(28 DiC with atherosclerosis,DiC without atherosclerosis and ischaemic colitis each)for validation purposes.Medical history was collected from the electronic database and patient records.Statistical analysis included chi-squared test,t-test,logistic and multivariate regression models.RESULTS Drug-induced colitis was detected in 211 endoscopically sampled biopsy specimens of the colon mucosa(7%of all screened colonoscopic biopsy samples);a total of 633 patients were included equally matched throughout the three groups(291 males,mean age:62.1±16.1 years).In the univariate analysis,DiC was associated with diuretics,dihydropyridines,glycosides,ASS,platelet aggregation inhibitors,nonsteroidal anti-inflammatory drugs(NSAIDs),statins and fibrates,and with atherosclerosis,particularly coronary heart disease,and hyperlipoproteinaemia.Echocardiographic parameters did not show substantial differences.In the multivariate analysis only fibrates[odds ratio(OR)=9.1],NSAIDs(OR=6.7)and atherosclerosis(OR=2.1)proved to be associated with DiC.Both DiC reassessment groups presented milder inflammation than ischaemic colitis.The DiC patients with atherosclerosis exhibited histological features from both DiC without atherosclerosis and ischaemic colitis.CONCLUSION Several drugs indicated for the treatment of cardiovascular and related diseases are associated with DiC.Atherosclerosis and microcirculatory disturbances seem to play an important pathogenetic role.

Expression of toxin-related human mono-ADP-ribosyltransferase 3 in human testes

Aim:To investigate wether the corresponding protein of mono-ADP-ribosyltransferase 3(ART3)mRNA is ex- pressed in human testes and,if so,whether the expression is cell type-specific.Methods:ART3 mRNA was deter- mined in human testes and sperm by reverse transcription-polymerase chain reaction(RT-PCR).The glycosyl- phosphatidylinositol linkage of ART3 was shown by treating ART3-transfected HEK-293-T cells with phospholipase C.Fluorescent activated cell sorter(FACS)-analyses were used to detect ART3 on mature spermatozoa and immuno- histological studies to detect the protein in testes.Results:ART3 protein was shown to be present in testes.It was found on spermatocytes only.It was absent from spermatogonia,spermatids and spermatozoa.The absence of ART3 from spermatozoa was confirmed by FACS-analysis.ART3 protein was detected neither within a seminoma nor on Leydig cells.Conclusion:Here we show for the first time that ART3 protein is expressed in testes in particular on spermatocytes,indicating that ART3 exerts a specific function only required at a particular stage of spermatogenesis.

Impact of preoperative chemotherapy on surgical results in 139 patients with locally advanced pancreatic cancer

Background:The establishment of preoperative chemotherapy(PCT)with FOLFIRINOX and gemcitabine/nab-paclitaxel in recent years has enabled resectability in many patients with initially locally advanced pancreatic cancer(LAPC).Nevertheless,information about the impact of PCT on surgical results is scarce.Methods:All patients with initial LAPC who received surgery after chemotherapy at the high-volume centre for pancreatic surgery of St.Josef-Hospital Bochum between 2015 and 2022 were included in this retrospective cohort analysis.Results:A total of 139 patients underwent surgery after pre-treatment with FOLFIRINOX(76.3%),gemcitabine/nab-paclitaxel(11.5%),both(5.8%)and other regimens(6.5%).Eighty-five tumors(61.2%)were resectable after PCT.R0 resection was achieved in 92.9%,R1 in 7.1%and R2 in 0%of cases.Fifty-four tumors were still not resectable at the time of surgery.Surgical results of the patients did not show increased postoperative mortality and morbidity compared to the literature data.Postoperative 30-day mortality was 1.4%.Rates for pancreas-specific complications[postoperative pancreatic fistula(POPF),delayed gastric emptying(DGE),postpancreatectomy hemorrhage(PPH),and others]were not increased.POPF occurred in 10.5%and DGE in 26.3%after pancreaticoduodenectomy.After distal pancreatectomy,POPF was detected in 37.5%and DGE in 12.5%.Median postoperative survival(31 vs.13 months)and overall survival after initial diagnosis(40 vs.20 months)were significantly longer in resected patients(P<0.001).Postoperative recurrence-free survival in resected patients amounted to 12 months.Conclusions:This study underlines that PCT allows resectability of primarily unresectable patients with LAPC without increasing perioperative mortality and morbidity.It may lead to a significant prolongation of recurrence-free and overall survival in resected patients after PCT.

Preservation of aberrant right hepatic arteries does not affect safety and oncological radicality of pancreaticoduodenectomy-own results and a systematic review of the literature

Background:Aberrant right hepatic arteries(aRHA)are frequently encountered during pancreaticoduodenectomy(PD).Their effects on surgical morbidity and resection margin are still debated.This study aimed to compare the short term and long term outcomes in patients with and without aRHA.Methods:A single-center retrospective analysis of 353 consecutive PD during a 5-year period was done.The type of arterial supply was determined preoperatively by CT and confirmed at surgery.Hiatt types III-VI included some type of aRHA and comprised the study group.Hiatt types I and II were considered irrelevant for PD and used as controls.Primary endpoints were the rates of major postoperative complications and the rate of R0-resection in cases of malignant disease.Secondary endpoints included duration of surgery,postoperative stay,number of harvested lymph nodes and survival in patients with pancreatic cancer.Own results were compared to existent data using a systematic review of the literature.Results:No aRHA had to be sacrificed or reconstructed.Surgical morbidity and specific complications such as post-pancreatectomy hemorrhage(PPH),pancreatic fistula and bile leak were the same in patients with and without aRHA.There was no significant difference in operative time,blood loss,length of ICU-and hospital stay.Patients with malignancy had similar high rates of R0-resection and identical number of harvested lymph nodes.Survival of patients with pancreatic cancer was not affected by aRHA.Conclusions:aRHA may be preserved in virtually all cases of PD for resectable pancreatic head lesions without increasing surgical morbidity and without compromising oncological radicality in patients with cancer,provided the variant anatomy is being recognised on preoperative CT and a meticulous surgical technique is used.

Histopathology of hepatocellular carcinoma-when and what

When do you need to take biopsies of the liver,and what information will you get is the topic of this review on hepatocellular carcinoma(HCC).If,clinically,the differential diagnosis of HCC after imaging is suggested,a biopsy has become obligatory as a diagnostic confirmation of HCC in the non-cirrhotic liver prior to definitive therapeutic interventions,as well as in a palliative therapy concept.In the case of hepatic lesions with an uncharacteristic contrast uptake,a biopsy should be performed immediately to confirm the diagnosis of HCC.After diagnosing HCC,a treatment strategy is evaluated.Further,the biopsy,or in case of surgical treatment,the resected tissue,shows us the different subtypes of HCC,with the steatohepatitic subtype being the most common and the lymphocyte-rich subtype being the least common.Further,the histological grade of HCC is determined according to the grading system of the WHO or the Edmonson and Steiner System.Through biopsies,HCC can be differentiated from intrahepatic cholangiocarcinoma or combined hepatocellular-cholangiocarcinoma or metastases of other malignant tumors,especially metastases of the gastrointestinal tract.In summary,biopsies are fundamental in the diagnosis of HCC.