Inflammatory myofibroblastic tumor of the distal common bile duct:Literature review with focus on pathological examination

Inflammatory myofibroblastic tumor(IMT)of the biliary tract is rare,and often difficult to diagnose or to distinguish from other tumors due to its atypical clinical presentation and nonspecific radiological features.Histologically,IMTs are(myo)fibroblastic neoplasms with a prominent inflammatory infiltrate.They are characterized by receptor tyrosine kinase gene rearrangements,most often involving an anaplastic lymphoma kinase(ALK)translocation.The final diagnosis of IMT depends on histopathology and immunohistochemical examination.In this manuscript,we provide a clinical and morphomolecular overview of IMT and the difficulties that may arise in using immunohistochemical and molecular techniques in diagnosing IMT.

Pediatric vascular tumors of the liver:Review from the pathologist’s point of view

Differential diagnosis of pediatric vascular liver tumors can be challenging due to inconsistent nomenclature,histologic overlap and the rarity of some entities.Here we give an up-to-date overview of the most important entities.We discuss the clinic,histology and pathophysiology of hepatic congenital and infantile heman-gioma,hepatic epithelioid hemangioendothelioma and hepatic angio-sarcoma.

Everolimus halts hepatic cystogenesis in a rodent model of polycystic-liver-disease

AIM To develop a MRI-based method for accurate determination of liver volume(LV) and to explore the effect of long-term everolimus(EVR) treatment on LV in PCK rats with hepatomegaly. METHODS Thirty-one female PCK rats(model for polycystic-liverdisease: PCLD) were randomized into 3 groups and treatment was started at 16 wk, at the moment of extensive hepatomegaly(comparable to what is done in the human disease). Animals received: controls(n = 14), lanreotide(LAN: 3 mg/kg per 2 wk)(n = 10) or everolimus(EVR: 1 mg/kg per day)(n = 7). LV was measured at week 16, 24, 28. At week 28, all rats were sacrificed and liver tissue was harvested. Fibrosis was evaluated using quantitative image analysis. In addition, gene(quantitative RT-PCR) and protein expression(by Western blot) of the PI3K/Ak T/m TOR signaling pathway was investigated. RESULTS LV determination by MRI correlated excellent with the ex vivo measurements(r = 0.99, P < 0.001). The relative changes in LV at the end of treatment were:(controls) +31.8%;(LAN) +5.1% and(EVR) +8.8%, indicating a significantly halt of LV progression compared with controls(respectively, P = 0.01 and P = 0.04). Furthermore, EVR significantly reduced the amount of liver fibrosis(P = 0.004) thus might also prevent the development of portal hypertension. There was no difference in phosphorylation of Akt(Threonine 308) between LAN-treated PCK rats control PCK rats, whereas S6 was significantly more phosphorylated in the LAN group. Phosphorylation of Akt was not different between controls and EVR treated rats, however, for S6 there was significantly less phosphorylation in the EVR treated rats. Thus, both drugs interact with the PI3K/Ak T/m TOR signaling cascade but acting at different molecular levels.CONCLUSION Everolimus halts cyst growth comparable to lanreotide and reduces the development of fibrosis. m TORinhibition should be further explored in PCLD patients especially those that need immunosuppression.

Limited influences of chemotherapy on healthy and metastatic liver parenchyma

AIM: To examine the expression of E-cadherin, β-catenin,γ-catenin, VEGF, and p53 in 39 patients with hepatic metastasis from colorectal cancer immunohistochemically.METHODS: The patients were divided into two groups:those (n = 16) who had no chemotherapy for at least 6 mo before the liver resections and those (n = 23)who were treated with chemotherapy before liver resections. A score from 0 to 3 was given for the number of positive cells and from 0 to 3 for the intensity of staining in these cells, in both healthy and metastatic liver parenchyma.RESULTS: No significant differences in the expression of E-cadherin, β- and γ-catenin, VEGF and p53, could be observed between patients who received and did not receive chemotherapy, in both normal and metastatic liver parenchyma.CONCLUSION: Despite the assumption that chemotherapy had an effect on liver metastasis, no influences were noticed immunohistochemically.

Near-infrared fluorescence guided esophageal reconstructive surgery: A systematic review

BACKGROUND After an esophagectomy, the stomach is most commonly used to restore continuity of the upper gastrointestinal tract. These esophago-gastric anastomoses are prone to serious complications such as leakage associated with high morbidity and mortality. Graft perfusion is considered to be an important predictor for anastomotic integrity. Based on the current literature we believe Indocyanine green fluorescence angiography(ICGA) is an easy assessment tool for gastric tube(GT) perfusion, and it might predict anastomotic leakage(AL).AIM To evaluate feasibility and effectiveness of ICGA in GT perfusion assessment and as a predictor of AL.METHODS This study was designed according to the PRISMA guidelines and registered in the PROSPERO database. PubMed and EMBASE were independently searched by 2 reviewers for studies presenting data on intraoperative ICGA GT perfusion assessment during esophago-gastric reconstruction after esophagectomy.Relevant outcomes such as feasibility, complications, intraoperative surgical changes based on ICGA findings, quantification attempts, anatomical data and the impact of ICGA on postoperative anastomotic complications, were collected by 2 independent researchers. The quality of the included articles was assessed based on the Methodological Index for Non-Randomized Studies. The 19 included studies presented data on 1192 esophagectomy patients, in 758 patients ICGA was used perioperative to guide esophageal reconstruction.RESULTS The 19 included studies for qualitative analyses all described ICGA as a safe and easy method to evaluate gastric graft perfusion. AL occurred in 13.8% of the entire cohort, 10% in the ICG guided group and 20.6% in the control group(P <0.001). When poorly perfused cases are excluded from the analyses, the difference in AL was even larger(AL well-perfused group 6.3% vs control group 20.5%, P <0.001). The AL rate in the group with an altered surgical plan based on the ICG image was 6.5%, similar to the well perfused group(6.3%) and significantly less than the poorly perfused group(47.8%)(P < 0.001), suggesting that the technique is able to identify and alter a potential bad outcome.CONCLUSION ICGA is a safe, feasible and promising method for perfusion assessment. The lower AL rate in the well perfused group suggest that a good fluorescent signal predicts a good outcome.

Systematic comparison of experimental and human obstructive cholestasis reveals conservation of canonical pathway activation and biomarkers relevant for cholestatic liver disease

Cholelithiasis-induced cholestasis is one of the most common causes of hospitalization due to gastrointestinal disease,yet considerable knowledge gaps exist in the pathogenesis of this disease.This can partially be explained by inadequate characterization of experimental cholestasis models.Here,we compared the transcriptional profile of commonly used mouse models for obstructive cholestasis and benchmarked them to human disease to identify the model(s)best suited for cholelithiasis-induced cholestasis research and to uncover conserved mechanisms involved in human and murine cholestasis.

Rare case of ascites several years after liver transplantation

Case report A 67-year-old male patient with a history of liver transplantation presented with complaints of progressive abdominal distention.He had a history of alcoholic cirrhosis complicated by hepatocellular carcinoma for which he underwent orthotopic liver transplantation in 2011.Afterwards,he developed end-stage renal disease,requiring hemodialysis in 2017.In 2018,the diagnosis of high-risk essential thrombocythemia(ET)(presence of the JAK2(V617F)mutation and advanced age without a history of thrombosis)was made.

Histologically proven hepatic steatosis associates with lower testosterone levels in men with obesity

Men with obesity often present with low testosterone(T)and sex hormone-binding globulin(SHBG)levels.Several mechanisms for this have been proposed,but as SHBG is secreted by hepatocytes and sex steroids undergo hepatic metabolization,this study investigates whether severity and histological components of nonalcoholic fatty liver disease(NAFLD)are associated with sex steroid levels in obese men.This cross-sectional study included 80 obese men(age:46±11 years;body mass index:42.2±5.5 kg m^-2).Serum levels of total T and estradiol(E.)were measured using liquid chromatography coupled with tandem mass spectroscopy(LC/MS-MS)and SHBG and gonadotropins by immunoassay.Liver biopsies were evaluated using Steatosis.Activity,and Fibrosis scoring.Participants with steatohepatitis had similar median(1st quartile-3rd quartile)total T levels(7.6[5.0-11.0]nmol l^-1 vs 8.2[7.2-10.9]nmol l^-1;P=0.147),lower calculated free T(cFT)levels(148.9[122.9-188.8]pmol 1-1 s 199.5[157.3-237.6] pmol l^-1;P=0.006),and higher free E.T ratios(10.0[6.4-13.9]×10^-3 vs 7.1[5.7-10.7]×10^-3;P=0.026)compared to men with only nonalcoholic fatty liver.Among the histological components of NAFLD.only steatosis was independently associated with total T(r=-0.331.P=0.003)and cFT levels(r=-0.255.P=0.025).Obese men with.steatohepatitis have even lower cFT levels compared to those without,an association mainly driven by grade of steatosis.Whether this reflects a subgroup of men with a more severe obesity-related phenotype or results from direct relations between hepatic steatosis and sex steroid metabolism needs further investigation.