Seventeen Years of Pediatric Liver Transplantation Experience for Cirrhosis and Hepatocellular Carcinoma.

OBJECTIVES: This was a retrospective analysis of liver transplant for pediatric patients with liver cirrhosis and hepatocellular carcinoma. MATERIALS AND METHODS: Fourteen pediatric patients with chronic liver disease and hepatocellular carcinoma underwent liver transplant from 2004 to 2021. Preexisting diseases were tyrosinemia (n = 6), progressive familial intrahepatic cholestasis type 2 (n = 2) and type 3 (n = 3), cryptogenic cirrhosis (n = 2), hepatitis B and D (n = 1), and biliary atresia (n = 1). RESULTS: Mean age was 9.43 ± 4.9 years (range, 13 months to 16 years). Three patients had 1 tumor, 4 had 2 tumors, and 7 had multiple (≥3) lesions. Six patients were classified as Pretreatment Extent of Disease Staging System for Hepatoblastoma (PRETEXT) stage IV, 3 as stage II, and 5 as stage I. Some patients received systemic chemotherapy before (n = 4) or after transplant (n = 3) or transarterial chemoembolization and microwave ablation pretransplant (n = 1). Hepatocellular carcinoma posttransplant recurrence was observed at 23, 47, and 108 months in 3 patients (21%). Recurrence sites were omentum (n = 1) and liver graft (n = 2). One patient was treated with hepatic resection, radiofrequency ablation, and radiotherapy, while the other received radiofrequency ablation and chemotherapy for graft tumor recurrence. Relapse-free patient survival rates were 92%, 82.5%, and 72.2% at 2, 4, and 10 years, respectively. Four recipients (28.5%) died; posttransplant cause of death was infection at 19 (n = 1) and 188 months (n = 1) or hepatocellular carcinoma recurrence at 79 (n = 1) and 165 months (n = 1). Median follow-up was 178 months (range, 13-204 months). Mean estimated survival was 171.25 ± 16.6 months. Overall patient posttransplant survival was 100%, 92.3%, 92.3%, 83%, and 72% at 1, 2, 5, 10, and 15 years, respectively. CONCLUSIONS: Hepatocellular carcinoma was mainly associated with inherited liver diseases in our pediatric series. Liver transplant provided a long-term survival advantage to pediatric patients with preexisting cirrhosis and hepatocellular carcinoma.

Factors affecting parametrial involvement in cervical cancer patients with tumor size ≤4 cm and selection of low-risk patient group

Objective: The primary aim of this study was to evaluate the factors affecting parametrial involvement in cervical cancer patients with tumor size ≤4 cm and selection of the low-risk patient group based on long-term oncologic outcomes. Material and Methods: Cervical cancer patients operated in the gynecologic oncology division between 2007 and 2013 were retrospectively evaluated. One-hundred and sixty-eight patients with tumor size ≤4 cm were identified. Of these, 159 (86.8%) underwent radical hysterectomy plus pelvic-para-aortic lymphadenectomy and nine (13.2%) underwent fertility-sparing surgery [radical trachelectomy (n=7); large conization (n=2)]. Factors affecting parametrial invasion, including lymphovascular space invasion (LVSI), deep stromal invasion (DSI), lymph node metastases, and tumor size, were evaluated. Statistical analyses were performed using SPSS 23.0 (IBM Corp., Armonk, NY, USA). Results: Median age was 49.5 years and median tumor size was 2.5 cm (0.45-4 cm). In both univariate and multivariate analyses, the risk of parametrial involvement was increased with LVSI with a hazard ratio (HR) of 3.45 [95% confidence interval (CI): 1.1-10.8] and DSI with a HR of 4.1 (95% CI: 1.18-14.8), while tumor size of ≤2 cm was only significant in univariate analyses. Furthermore, 26 early-stage patients were identified with low-risk factors and they had no parametrial involvement, lymph node metastases, recurrence, or death from disease over 77 months. Conclusion: Parametrial involvement in low-risk cervical cancer is very rare and less radical procedures may be safe in these patients.

Liver Transplant for Hepatocellular Carcinoma: Pathologic Point Of View.

Primary liver cancer is the fifth most common cancer overall and the second most common cause of cancer mortality worldwide. Hepatocellular carcinoma accounts for up to 90% of all primary hepatic malignancies and represents a major international health problem. It is a complex and heterogeneous malignancy, frequently occurs in the setting of a chronically diseased organ, and has multiple confounding factors. Liver transplant for hepatocellular carcinoma has been established as a standard treatment in selected patients. Liver resection and locoregional therapies could be other options for treatment. Pathologic evaluation of hepatocellular carcinoma is a complicated process that includes tumor grading and evaluation of microvascular invasion. Although macrovascular invasion can be detected with imaging techniques, microvascular invasion is diagnosed pathologically. Pathologic evaluation provides additional information about the tumor biology, using immunohistochemical and molecular methods to predict patient outcomes. Hepatocellular carcinoma requires a multidisciplinary approach to determine the most appropriate treatment, as well as requires accurate timing of various treatments for optimal outcomes.

Liver Transplant for Nonhepatocellular Carcinoma Malignancy.

Liver transplant is now an acceptable and effective treatment for specific nonhepatocellular malignancies. Worldwide, hilar cholangiocarcinoma accounts for 3% of all primary gastrointestinal malignancies and for 10% of primary hepatobiliary malignancies. For patients who have early-stage, unresectable cholangiocarcinoma, liver transplant preceded by neoadjuvant radiotherapy can result in tumor-free margins, accomplish a radical resection, and treat the underlying primary sclerosing cholangitis when present. Hepatic epithelioid hemangioendothelioma is a rare tumor of vascular origin with a variable malignant potential. Excellent results have been reported with liver transplant for patients with unresectable hepatic epithelioid hemangioendothelioma, with 1-year and 10-year survival rates of 96% and 72%. Hepatoblastoma is the most common primary hepatic malignancy in children. The long-term survival rate after transplant ranges from 66% to 77% in patients with unresectable tumors and good response to chemotherapy. Metastatic liver disease is not an indication for liver transplant, with the exception of cases in which the primary tumor is a neuroendocrine tumor. Indication for liver transplant for hepatic metastasis from neuroendocrine tumors is mainly for patients with unresectable tumors and for palliation of medically uncontrollable symptoms. Posttransplant survival in those patients with low tumor activity index is excellent, despite recurrence of the tumor. Some recent data on liver transplant for unresectable hepatic metastases from colorectal cancer have reported limited survival benefits compared with previous reports. However, due to the high rate of tumor recurrence in a very short time after liver transplant, especially in the era of organ shortage, this indication has not been favored by the transplant community. The indications for liver transplant for nonhepatocellular carcinoma malignancy and its limitations have evolved dramatically over the past decades and will continue to be redefined through future research and investigations.

Evaluation of safety and efficacy of liver biopsy following liver transplant.

OBJECTIVES: Liver biopsy is a diagnostic tool for liver pathology after liver transplant. However, biopsy can cause life-threating complications. There is limited knowledge about efficacy and complications of liver biopsy after liver transplant. Our aim was to evaluate the risk and benefit of liver biopsy after liver transplant and quality of biopsy specimens. MATERIALS AND METHODS: We retrospectively analyzed all liver biopsies performed after liver transplant between January 2000 and October 2014. All patients were monitored for minimum 24 hours after biopsy. RESULTS: We performed 245 liver biopsies in 159 liver transplant patients. Fifteen biopsies (6%) were nondiagnostic. In the samples, there were 102 cases (41%) of acute rejection, 79 cases (35%) of cholangitis, and 49 cases (20%) of cholestasis observed. Complications after biopsy were seen in 23 patients (9%) and biopsies. There were 7 patients who had severe abdominal pain followed by fever. We diagnosed 4 patients who had intercostal/subcapsular bleeding and 12 patients who had vasovagal reaction. All patients were treated with analgesic agents and monitored for 24 hours. No blood transfusion or surgery was required. CONCLUSIONS: Liver biopsy after liver transplant is an invasive diagnostic tool for liver pathology. However, it can be used safely in experienced centers.

A single-center retrospective clinicopathologic study of endomyocardial biopsies after heart transplant at Baskent University Hospital in Ankara, 1993-2014.

OBJECTIVES: The purpose of this study was to investigate the frequency and prognostic importance of acute cellular rejection after heart transplant. MATERIALS AND METHODS: All 84 heart transplant patients at our center from January 1993 to January 2014, including all 576 endomyocardial biopsies, were evaluated with retrospective review of clinical records and endomyocardial biopsies. Routine and clinically indicated endomyocardial biopsies after heart transplant were graded for acute cellular rejection (2005 International Society for Heart and Lung Transplantation Working Formulation). Survival analysis was performed using Kaplan-Meier method. RESULTS: There were 61 male (73%) and 23 female recipients. Median age at heart transplant was 29 years (range, 1-62 y). Posttransplant early mortality rate was 17.9% (15 patients). In the other 69 patients, 23 patients died and 46 patients (66.7%) were alive at mean 69.3 ± 7.2 months after heart transplant. Mean follow-up was 35.4 ± 29.8 months (range, 0.07-117.5 mo). Mean 8.4 ± 4.2 endomyocardial biopsies (range, 1-19 biopsies) were performed per patient. Median first biopsy time was 7 days (range, 1-78 d). The frequency of posttransplant acute cellular rejection was 63.8% (44 of 69 patients) by histopathology; 86% patients experienced the first episode of acute cellular rejection within 6 months after transplant. There were 18 patients with acute cellular rejection ≥ grade 2R on ≥ 1 endomyocardial biopsy in 44 patients with acute cellular rejection. No significant difference was observed between survival rates of patients with grade 1R or ≥ grade 2R acute cellular rejection, or between survival rates of patients with or without diagnosis of any grade of acute cellular rejection. Acute cellular rejection was not related to any prognostic risk factor. CONCLUSIONS: Acute cellular rejection had no negative effect on heart recipient long-term survival, but it was a frequent complication after heart transplant, especially within the first 6 months.