Detection of human herpesvirus-6 in adult central nervous system tumors: predominance of early and late viral antigens in glial tumors.

The purpose is to determine the incidence of active and latent human herpesvirus-6 (HHV-6) infection in a large cohort of adult primary and recurrent CNS tumors. We screened a tissue microarray (TMA) containing more than 200 adult primary and recurrent CNS tumors with known clinical information for the presence of HHV-6 DNA by in situ hybridization (ISH) and protein by immunohistochemistry (IHC). One hundred six of 224 (47%) CNS tumors were positive for HHV-6 U57 Major Capsid Protein (MCP) gene by ISH compared to 0/25 non tumor control brain (P = 0.001). Fourteen of 30 (47%) tumors were HHV-6 MCP positive by nested PCR compared to 0/25 non-tumor brain controls (P = 0.001), revealing HHV-6 Variant A in 6 of 14 samples. HHV-6A/B early (p41) and late (gp116/64/54) antigens were detected by IHC in 66 of 277 (24%) (P = 0.003) and 84 of 282 (35%) (P = 0.002) tumors, respectively, suggesting active infection. HHV-6 p41 (P = 0.645) and gp116/64/54 (P = 0.198) antigen detection was independent of recurrent disease. Glial tumors were 3 times more positive by IHC compared to non glial tumors for both HHV-6 gp116/64/54 (P = 0.0002) and HHV-6 p41 (P = 0.004). Kaplan Meier survival analysis showed no effect of HHV-6 gp116/64/54 (P = 0.852) or HHV-6 p41 (P = 0.817) antigen detection on survival. HHV-6 early and late antigens are detected in adult primary and recurrent CNS tumors more frequently in glial tumors. We hypothesize that the glial-tropic features of HHV-6 may play an important modifying role in tumor biology that warrants further investigation.

Feasibility of metronomic maintenance chemotherapy following high-dose chemotherapy for malignant central nervous system tumors.

BACKGROUND: Children less than 5 years of age with malignant central nervous system (CNS) tumors, continue to have a high rate of morbidity and mortality following administration of conventional therapy. In an attempt to avoid the neurologic sequelae associated with craniospinal radiation, strategies such as high-dose chemotherapy (HDCT) followed by peripheral stem cell rescue have been used successfully. Metronomic chemotherapy has also been reported as a potential new treatment strategy in solid tumors, particularly in adults. PROCEDURE: A retrospective chart analysis was performed on 10 patients less than 5 years of age with CNS tumors treated with metronomic chemotherapy shortly after HDCT as part of their clinical care. RESULTS: Metronomic chemotherapy was associated with minimal toxicity and all patients maintained a good quality of life. At the time of this report, all 10 patients are alive. Two patients have relapsed, and the remaining eight, including six patients with metastatic disease, continue to have stable clinical and radiographic disease at a mean of 20 months from the time of diagnosis. CONCLUSIONS: Metronomic chemotherapy in this patient population is feasible and shows encouraging preliminary results, especially in patients with metastatic disease who have not received craniospinal radiation. Further investigation of this strategy in newly diagnosed patients with CNS tumors is warranted.

Human herpesvirus 6 rhombencephalitis in immunocompetent children.

This article describes the clinical presentation, diagnostic workup, and neurologic outcome of 3 immunocompetent pediatric patients diagnosed with human herpesvirus 6 (HHV6) rhombencephalitis. Presentation of HHV6 rhombencephalitis included new onset seizures, ataxia, encephalopathy, and opsoclonus-myoclonus. Neurologic examination revealed cranial neuropathies, cerebellar dysfunction, and extremity weakness. Magnetic resonance imaging abnormalities located in the cerebellum, basal ganglia/thalamus, and cerebral hemispheres were detected in 2 patients. Diagnosis of HHV6 encephalitis was made by real-time and nested polymerase chain reaction of serum and cerebrospinal fluid. The HHV6 variant A was detected in 2 patients by sequence analysis, and HHV6 protein was detected by immunomicroscopy in a patient who underwent biopsy secondary to progressive clinical and neuroradiographic findings. Therapy with intravenous ganciclovir did not correlate with resolution of neurologic symptoms, despite eventual non-detectable HHV6. Human herpesvirus 6 should be considered in the differential diagnosis of unexplained cases of rhombencephalitis in immunocompetent children. Features may be rapidly progressive and include profound encephalopathy, seizures, ataxia, and opsoclonus-myoclonus.

Role of endoscopic retrograde cholangiopancreatography in diagnosis and management of congenital choledochal cysts: 28 pediatric cases.

BACKGROUND/PURPOSE: Management of choledochal cysts consists of surgical excision and hepaticojejunal anastomosis. Endoscopic retrograde cholangiopancreatography (ERCP) can be used to resolve complications and to evaluate the biliary tract and pancreatobiliary duct junction. Our aim was to underline the importance of ERCP for optimal management. METHODS: From 2005 to 2011, 28 patients were reviewed (21 female, 7 male; mean age, 5.71 years; range, 2-16 years). After imaging, all patients underwent elective ERCP and were referred for surgery. RESULTS: Choledochal cyst was diagnosed at ultrasound and magnetic resonance cholangiopancreatography in all examined patients; common biliopancreatic duct was diagnosed in 3 (20%) of 15 patients at magnetic resonance cholangiopancreatography and in none at ultrasound. Endoscopic retrograde cholangiopancreatography showed choledochal cyst in all patients and common biliopancreatic duct in 19 (68%) of 28 patients. Twelve patients underwent sphincterotomy. All patients underwent surgical extrahepatic biliary tree resection and hepaticojejunal anastomosis. Mean period of hospitalization was 9.5 days (range, 6-13 days). No major complications related to ERCP were observed. Two patients needed postoperative ERCP for complications (pancreatitis during follow-up). CONCLUSIONS: In our pediatric experience, ERCP is feasible and safe. It can rule out other possible biliary tract anomalies and help plan the timing and choice of the appropriate surgical procedure.

Surgery or endoscopy to treat duodenal duplications in children.

BACKGROUND/PURPOSE: Gastrointestinal duplications (duodenal duplications [DDs]) are a rare congenital malformation generally located in or adjacent to the medial border of the duodenal wall. The goal of therapy is surgical excision. Conservative endoscopic management represents an alternative option. AIM: The aim of the study was to highlight the role of endoscopic ultrasound (EUS) in guiding the endoscopic or surgical treatment of DD. METHODS: Between 2002 and 2010, 6 patients (2 male; mean age, 7.83 years; range, 2-18 years), all with recurrent acute pancreatitis, were diagnosed with DD by ultrasound and magnetic resonance imaging. Endoscopy was always performed together with EUS (Olympus UM-3R 20-MHz radial miniprobe, Tokyo, Japan). An endoscopic section of the common duodenal-DD wall, using a precut needle or sphincterotome, was chosen by EUS when the biliary tree was not involved in the DD. Otherwise, surgery with duodenotomy and complete opening of the common wall was used. RESULTS: After EUS evaluation, endoscopic treatment was successfully performed in 4 patients, 2 of whom required surgical treatment. Bleeding occurred in 1 patient after endoscopic resection and in 1 patient after surgery. The mean follow-up time without pathologic signs was 3.3 years (range, 0.25-8). CONCLUSIONS: Endoscopic ultrasound can effectively guide surgical or endoscopic therapies. Bleeding is a possible complication.