Gonca Özgün

Clinical Findings and Explant Liver Histology in Crigler Najjar Disease

Introduction We evaluated pediatric patients with Crigler Najjar disease who received LT at our center. Materials and Methods We reviewed the clinical and laboratory data of patients with Crigler Najjar disease who received LT at Başkent University from 2001-2017. Histopathologic examinations of explanted livers were also recorded. Results There was total of 7 patients (5 female 71.4%). The mean age at the time of LT was 5±7.1 years (range: 0.2-17.5 y). The liver function tests before LT were: total bilirubin: 31.28±7.3 mg/dL (range: 20.7-43.3 mg/dL), direct bilirubin: 1.39±1.19 mg/dL (range: 0.46-3.93 mg/dL), AST: 174±330 mg/dL (range: 24-922 IU/L), ALT: 79±88 mg/dL (range: 19-276 IU/L), GGT: 67±53 mg/dL (range: 27-184 U/L), ALP: 569±327 mg/dL (range: 115-1055 IU/L). Patients were given 11±3 hours (range: 8-16 hours) phototherapy (6/7 patients), phenobarbital (5/7 patients), cholestyramine (3/7 patients) before LT. Plasmapheresis was used in 1 patient to decrease bilirubin levels before LT. The mean body weight of the patients at the time of transplant was 20.9±19.6 kg (range: 6.7-58 kg). The donor was father in 5 and mother in 2 LT. Left lateral lobe was used in 5, left lobe was used in 1 and right lobe was used in 1 patient. Patients were followed up for 5.83±4.3 years (range: 1-11.5 y). Postoperative complications included hepatic artery thrombosis in 2 patients, hepatic vein thrombosis in 1, bile leak in 2, acute cellular rejection in 2, pneumothorax in 1, primary graft dysfunction and cholestasis in 1. One patient had neurologic sequela and died after vomiting and aspiration during his sleep at 1 year posttransplant. One patient has mild mental retardation. Other patients are alive with normal developmental milestones. One patient had cirrhosis and homozygous mutation in UGT1A1 gene consistent with Crigler Najjar type 1. She was only given ursodeoxycholic acid and cholestyramine as treatment before liver transplant. She is doing fine without any neurologic deficit after LT. Explanted livers showed normal structure in all patients except one. 5 patients had mild hepatocanalicular cholestasis, cirrhotic patient additionally had dilated bile ducts filled with cholestatic plugs and prominent ductular and vascular proliferation. 1 patient without cirrhosis had mild portoportal fibrosis, as well as mild bile ductular proliferation. 5 patients had lymphomononuclear inflammation in the portal areas. 3 patients showed ballooning degeneration in the hepatocytes.3 patients had neutrophilic infiltration in the paranchyme and subcapsular areas. 1 patient had diffuse microvesicular steatosis. Conclusions Severe form of Crigler Najjar disease can be successfully cured by LT. Mild increase in liver function tests other than bilirubin may be recorded before surgery. Histopathological explants may show cholestatic changes and portal/paranchymal inflammation. This finding may be secondary to co-existing liver diseases or Crigler Najjar disease itself.

Baskent University Expanded Criteria for Hepatocellular Carcinoma: The Importance of the Histopathological Features as a Part of the Evaluation Criteria for Liver Transplantation

Introduction Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver and is responsible for up to 90% of all liver tumors. Liver transplantation remains the best option for patients with HCC. This study aimed to determine the impact of the histopathological features of the primary tumor to the long-term outcome of liver transplants for HCC. Materials and Methods Among 554 liver transplants performed between 1988 and 2016, only 61 was for the treatment of HCC. All histopathological prognostic criteria such as tumor grade, tumor size, the number of tumor nodules, the presence of lymphovascular invasion (LVI), and tumor necrosis were reevaluated. Patients classified into 2 groups; Group 1: patients who underwent LT within Milan criteria, and Group 2: patients who underwent LT beyond Milan criteria. Also, we divided Group 2 patients into 2 subgroups; Group 2a: tumors with favorable histologic features, Group 2b: tumors with unfavorable histologic characteristics. The mean follow-up time was 89.7±47 months. Results The histopathological mean tumor diameter was found 3.2 ±2.1 cm (1-9 cm) in 61 (M/F: 52/9) patients. Total 24 recipients died because of HCC at a mean time of 38.8 ±25 months posttransplant. The disease-free survival found to decrease with the increasing degree of grade and tumor size (p<.01). A tumor size >5 cm showed significant correlation with tumor recurrence and lower survival (p<.05).Patients who had LVI and also tumor necrosis tended to show lower survival (p<.01). The mean survival of Group 1 and Group 2 were 111.4±42 and 72.5±43.7 months, respectively. Overall 10-year survival was 76% and 43% for Group 1 and Group 2, respectively (p<.05). Overall 10-year survival was 75% and 28% for Group 2a and Group 2b, respectively (p<.01). Overall 10-year survival rates of Group 1 and Group 2a were similar to each other (p>.05).Whereas patients in Group 2b with unfavorable histology showed poorer prognosis compared to patients who did not have these histopathological parameters (p<.01). Discussion Based on our results; we propose an algorithm to evaluate HCC for the decision of transplant. If HCC radiologically classified as “within Milan”, transplantation could be the treatment modality. If HCC classified as “beyond Milan”, a liver biopsy should be performed. If the histopathological characteristics were favorable, the treatment modality should be the same as tumors classified “within Milan”. If the tumor has unfavorable histologic characteristics, transplantation option could be still beneficial and curative for at least 50% of the patients in 5 years and 28% of the patients in 10 years. Conclusion Tumor biology is the most critical parameter that predicts the survival of patients with HCC and the histopathological parameters must take part in the selection criteria of the patients for LT.

Pathological analysis of cystic lesions of the bones: a retrospective single-center 10-year overview

Objective: Many different neoplastic and non-neoplastic lesions involve the skeletal system. Clinical and radiological tools primarily assess the nature of these lesions.The aim of this study was to analyze the cystic bone lesions in a pathologic point of view. Methods: All bone cysts between 2002 and 2013 retrospectively evaluated under the guidance of clinical information and radiological images. Descriptive data such as age, gender, tumor site, symptoms, and clinical and radiological findings obtained from the hospital’s database system. Results: There were 96 cystic bone lesions; 47 were aneurysmal bone cysts (ABCs), 37 were simple bone cysts (SBCs), one was a lesion with features of both ABC and SBC, four were intraosseous ganglia, four were epidermoid cysts, and three were hydatid cysts. The mean ages of the patients with ABCs and SBCs were 18.7 ± 12.8 years (range, 3-75 years) and 23.8 ± 13.3 years (range, 3-62 years), respectively. Most of the lesions located in the long bones. Conclusions: Cystic lesions of the bone rarely encountered in daily pathology routine. As with all conditions affecting the skeletal system, one of the most important steps towards an accurate pathological diagnosis is to perform with clinical and radiological information while evaluating the patients.

Liver Cirrhosis in a Patient with Crigler Najjar Syndrome

Abstract Introduction: Crigler Najjar (CN) disease is a genetic disorder which results in increased unconjugated bilirubin level. Liver parenchyma was previously considered structurally normal. Recent reports describe significant fibrosis in the liver parenchyma of patients with CN syndrome. Case report: We present a patient with persistent unconjugated hyperbilirubinemia, clinically diagnosed as CN-2, with a UGT1 A1 p. H39D (c.115C > G) (His → Asp) mutation. She required hepatic transplantation at the age of 17.5 years for biliary cirrhosis. Explanted liver histopathology revealed regenerative cirrhotic nodules with dilated bile ducts filled with bile plugs. Conclusion: CN can develop significant hepatic fibrosis/cirrhosis requiring liver transplantation.

Enhancer of zeste homologue 2 (EZH2) expression in synovial sarcomas as a promising indicator of prognosis

Synovial sarcoma (SS) is a type of soft-tissue sarcoma, often linked to poor survival. Although overexpression of enhancer of zeste homologue 2 (EZH2) has been associated with poor prognosis in different tumors, a few studies investigated this link in SS. Here, we analyzed the relationship between EZH2 expression and prognostic factors in SS. We included 29 patients with SS. Immunostaining of EZH2 was performed with (D2C9) XPTM Rabbit mAb antibody, and the results were classified as low EZH2 expression (negative or weak expression) and high EZH2 expression category (moderate or strong expression). Analysis of survival in relation to prognostic factors was performed with Kaplan-Meier survival curves and Cox proportional hazard regression analysis. Our sample included 19/29 female and 10/29 male patients, with age range 16-63 years. The tumor diameter ranged from 2 to 15 cm. Necrosis was observed in 15/29 cases. Sixteen cases had >10 mitoses per 50 high-power fields (HPFs). Out of 29 cases, 14 showed low and 15 had high EZH2 expression. Statistically significant results were obtained for the association between the presence of metastasis and necrosis (p = 0.042), high EZH2 expression and distant metastasis (p = 0.018), high EZH2 expression and necrosis (p = 0.016), and high EZH2 expression and the tumor size >5 cm versus tumor size ≤5 cm (p = 0.014). Patients with all of the following: the tumor size ≤5 cm, low EZH2 expression, and without necrosis and distant metastasis had significantly longer survival time. Our results are consistent with previous studies, suggesting that EZH2 overexpression is an indicator of poor prognosis in SS.