Beata Gierej

Epithelioid hemangioendothelioma of the liver as a rare indication for liver transplantation.

AIM To investigate the indications and outcomes of liver transplantation for hepatic epithelioid hemangioendothelioma (HEHE). METHODS Between 1989 and August 2013, in the Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, 1306 orthotopic liver transplantations (OLTx) were performed, including 72 retransplantations. Unresectable HEHE was an indication for OLTx in 10 patients (0.8% of primary OLTx), the mean age of the patients was 40.5 ± 13.3 years (range 23-65 years), and the male-to-female ratio was 2:8. Kaplan-Meier survival analysis in HEHE, hepatocellular carcinoma (HCC), and other OLTx recipients groups was performed. The differences in mortality were compared using the χ(2) test. A P-value < 0.05 indicated statistical significance. RESULTS No concomitant liver disease was found in any patient. There was no neoadjuvant chemotherapy or radiotherapy. Liver function test results were normal in most of the patients. The levels of alpha-fetoprotein, carcinoembryonic antigen, and carbohydrate antigen 19-9 were normal. In immunohistochemical staining, the neoplastic cells were positive for factor VIII-related antigen, CD31, and CD34, which are endothelial cell markers, and negative for cytokeratin 19, cytokeratin 7, and HepPar-1. Nine patients were alive without tumor recurrence. One patient died 2 mo after OLTx due to septic complications. No morbidity was observed. Maximum follow-up was 11.4 years, with a minimum of 1 mo. The cumulative survival rate at the end of follow-up in HEHE patients was 87.5% compared with 54.3% in the HCC group and 76.3% in the other OLTx recipients group (χ(2) test = 1.784, df = 2, P = 0.409). CONCLUSION Unresectable HEHE, without extrahepatic metastases is an excellent indication for liver transplantation. Long-term survival is very good and much better than in HCC patients and the entire group of OLTx patients.

C4d in acute rejection after liver transplantation and its usefulness in differential diagnosis between acute liver rejection and hepatitis C recurrence.

BACKGROUND Acute liver graft rejection is still a common complication after liver transplantations. The diagnostics of this process is based on histological findings, resembling the presentation of HCV infection. Correct differentiation between acute rejection and recurrent HCV hepatitis is very important because of differences in treatment. From the practical point of view, C4d could be used in liver transplantology for differential diagnostics of acute graft rejection and recurrence of HCV infection. MATERIAL AND METHODS The study was performed in liver graft biopsies obtained from 57 patients with acute rejection and from 26 patients with hepatitis C recurrence. The sections were probed immunohistochemically using antibody specific to C4d. The following parameters were analyzed statistically: the percentage of immunoreactive biopsies, the localization of C4d deposits, and the relationships between C4d-positive biopsies with acute rejection and hepatitis C recurrence. RESULTS Within liver graft biopsies with acute rejection and hepatitis C recurrence, the immunoreactivities of C4d were present almost exclusively along venous, arterial, and arteriolar endothelium in the portal spaces. C4d deposits were found in 33 patients with acute rejection (57.9%) and in 17 patients with hepatitis C recurrence (65.38%). The study demonstrated no statistically significant difference in C4d expression in liver biopsies from acute graft rejection patients as compared with HCV infection recurrence (chi-squared =1.5566774 df=1 p=0.45560). Both groups demonstrated positive reactions within biopsies. CONCLUSIONS Our results suggest that C4d deposits are insufficient in differentiation between both examined liver pathologies, but could be a useful marker in the diagnostics of acute liver rejection with humoral component.

Prostate cancer in deceased organ donors: loss of organ or transplantation with active surveillance?

INTRODUCTION Prostate cancer has become an important clinical issue within deceased organ donors. There is still a considerable number of undiagnosed cancers, especially in early stage, despite frozen section analysis. The aim of the study was to evaluate outcomes of orthotopic liver transplants (OLTx) with organs from donors with prostate cancer. MATERIAL AND METHODS A retrospective analysis was performed in deceased liver donors whose prostate glands were harvested for histologic examinations because of prostate cancer suspicion. The study group consisted of 72 men reported as potential liver donors between 2011 and November 2017. Prostate glands were primarily assessed by frozen sections and afterward in routine examination. Generally cancer diagnosed in frozen specimen was not considered for OLTx. Recipients who received an organ from the donor with prostate cancer were actively surveilled. RESULTS There were 19 cases (26.40%) of prostate cancer diagnosed among the study group. In 12 cases diagnosis was made by frozen section assessment, of which 11 organs were disqualified from OLTx and 1 was transplanted. In 7 cases prostate cancer was diagnosed after OLTx in final routine histologic examination. Finally, 8 recipients (5 men and 3 women) received a new organ. Only 1 died during the perioperative period. In the remaining 7 patients the perioperative period was uneventful and no disease transmission was observed during follow-up. CONCLUSIONS Diagnosis of prostate cancer in donors should not be treated as a contraindication for OLTx because the risk of disease transmission is low. Potential recipients must be fully informed and kept under oncological surveillance.

Expression of resistin in the liver of patients with non-alcoholic fatty liver disease

Adipokines are cytokines that presumably connect the pathologies of metabolic syndrome. One of the adipokines is resistin, the role of which in insulin resistance, obesity, and non-alcoholic fatty liver disease (NAFLD) needs to be determined. Liver biopsy specimens were obtained intraoperatively from 214 obese patients. Histological assessment was based on NAFLD activity score according to Kleiner. Statistical analysis involved semi-quantitive immunohistochemistry assessment of resistin staining and: NAFLD status in obese patients compared with a non-obese control group, selected clinical data (age, sex, body mass index - BMI), selected biochemical data, comorbidities (hypertension, type 2 diabetes mellitus, dyslipidaemia), and metformin treatment in patients with type 2 diabetes mellitus. Resistin expression was observed in the histiocytes of inflammatory infiltrate, Kupffer cells, and histiocytes surrounding the hepatocytes with steatosis. There was a positive correlation between the total expression of resistin and: (1) NAFLD advancement (NAFLD Activity Score- NAS), (2) AST, ALT, BMI, glucose, insulin, Homeostasis Model Assessment (HOMA), LDH, GGT, triglycerides (TG), and glycated haemoglobin (HbA1c). Resistin expression was more intense in patients with type 2 diabetes mellitus and dyslipidaemia and less intense in the control group. Resistin probably plays a role in the pathogenesis of hepatic insulin resistance and aggravates pathologic changes in the liver of patients with NAFLD.

A rare but life-threatening complication in liver transplant recipients

Graft versus host disease (GvHD) occurs in as little as 1–2% of cases after liver transplantation (LT), but is probably under-diagnosed and under-reported. Skin rash, diarrhoea, and/or fever are early symptoms of GvHD, and the most common causes of death are sepsis or gastrointestinal bleeding as a result of bone-marrow involvement. The delay in diagnosis as well as lack of standard treatment contributes to the high lethality of GvHD.

A rare CD5-positive subgroup of diffuse large B-cell lymphoma – clinical, morphological and immunophenotypic features in Polish patients

The aim of the study was to assess the incidence of CD5-positive diffuse large B-cell lymphoma (DLBCL) in the Polish population and to describe its morphologic and clinical characteristics. The study included 36 patients with CD5-positive DLBCL, diagnosed and treated in the Maria Skłodowska-Curie Institute and Oncology Centre, Warsaw, Poland and the Medical University of Warsaw, Poland in the years 2002-2013. The control group consisted of 28 patients with CD5-negative DLBCL. CD5-positive DLBCL accounted for 6.26% of all DLBCL cases diagnosed in the Maria Skłodowska-Curie Institute and Oncology Centre in the years 2008-2012. The incidence is comparable to other European countries, lower than noted in Japan and higher than in the US. Patients with CD5-positive DLBCL, in comparison to the CD5-negative group, were characterized by: (1) older age (≥ 60 vs. younger) and worse general status (ECOG ≥ 2 vs. < 2), (2) lower frequency of complete remission (CR), (3) higher expression of unfavorable prognostic factors (BCL2, FOXP1, CD44) and MMP-9, and (4) lower expression of favorable prognostic factors (CD30, cyclin D1, cyclin D3) and TIMP-2.

Angiogenesis in CD5-positive Diffuse Large B Cell Lymphoma: A Morphometric Analysis

BACKGROUND CD5-positive diffuse large B cell lymphoma (DLBCL) is the least frequent immunohistochemical subgroup of DLBCL. The relatively little available data suggests a worse outcome in this population, resulting from a resistance to chemotherapy. OBJECTIVES The aim was the comparative assessment of angiogenesis in both CD5-positive and CD5-negative DLBCL, as well as in lymphatic tissues without lymphoproliferative diseases. MATERIAL AND METHODS The analysis included 36 cases of CD5-positive DLBCL (19 females and 17 males) aged 29-87 years (mean age 69), diagnosed and treated in the Maria Sklodowska-Curie Institute and Oncology Center and Medical University of Warsaw in 2002-2013. The control group comprised 28 cases of CD5-negative DLBCL (14 females and 14 males) aged 24-82 years (mean age 58.5). The secondary control group (13 cases) consisted of normal lymphatic tissue obtained from patients without lymphoproliferative diseases. The level of angiogenesis was assessed on the basis of immunohistochemical CD34, vWF and HIF1α expression measured using morphometric methods. RESULTS CD5-positive DLBCL, in comparison to CD5-negative DLBCL, was characterized by: (1) higher mean of total blood vessel area, (2) higher mean total ratio of blood vessel area and staining intensity, (3) higher mean of total blood vessel area in regions defined as hot spots, (4) higher mean of total ratio of blood vessel area and staining intensity in hot spots. The measurements in lymph nodes without lymphoproliferative diseases lay between the values obtained in both DLBCL subgroups. CONCLUSIONS We observed a significant exacerbation of angiogenesis in CD5-positive DLBCL in comparison to the CD5-negative subgroup, possibly explaining its more aggressive clinical course. Our data does not substantiate the hypothesis that angiogenesis is more pronounced in frequent CD5-negative DLBCL subgroup in comparison to benign lymphatic tissue.