Stereotactic body radiation therapy in hepatocellular carcinoma and cirrhosis: evaluation of radiological and pathological response.

BACKGROUND: Loco-regional therapies for cirrhotic patients with hepatocellular carcinoma (HCC) who are awaiting liver transplantation (OLT) attempt to prevent tumor progression. However, there is limited data regarding the efficacy of stereotactic body radiation therapy (SBRT) as loco-regional treatment. METHODS: From 2006 to 2009, 27 HCC patients (AJCC I, II) listed for OLT underwent SBRT. Thirty-nine lesions were treated and 27 assessed radiologically. Seventeen patients had OLT, liver explants were analyzed and 22 lesions underwent pathological evaluation. RESULTS: In a cumulative analysis of all imaging, 30% had complete response, 7% had partial response, 56% were stable, and 7% had progression of disease. Of the 22 pathologically evaluated lesions, 37% were responders: 14% with complete response, 23% with partial response, and 63% with no response. Side effects from SBRT were recorded in three patients, which included nausea in two and liver decompensation in one. CONCLUSION: SBRT achieves total or partial radiological response in 37% of patients and total or partial pathological response in 37% of patients with early HCC in the setting of cirrhosis. SBRT may be a safe and effective alternative for local tumor control in patients with HCC and cirrhosis awaiting OLT.

Immunosuppressant-induced endothelial damage and pulmonary arterial hypertension.

Cyclosporine A, used to prevent graft-versus-host-disease, is known to induce endothelial injury. Endothelial dysfunction is an important feature of pulmonary arterial hypertension (PAH). In this article, we describe 2 children who developed cyclosporine-induced acute respiratory distress syndrome. Lung biopsy showed patchy loss of endothelial caveolin-1 and von Willebrand factor to occur early. Significant loss of endothelial caveolin-1 was associated with robust expression of caveolin-1 in smooth muscle cells with subsequent neointima formation leading to fatal PAH. Thus, patients who develop acute respiratory distress syndrome after immunosuppressive therapy are at risk of developing PAH.

A novel two-dimensional echocardiographic finding in cardiac amyloidosis.

BACKGROUND: A number of echocardiographic findings characteristic of cardiac amyloidosis (CA) have been described, each with limitations. METHODS: A distinctive wall motion pattern of preserved myocardial thickening at left ventricular apex with hypokinesis in basal and midsegments was observed in two patients with biopsy proven CA. Following this observation, endomyocaradial biopsy files beginning in 2007 were reviewed. Seven consecutive patients with documented CA were identified. Two-dimensional (2D) echocardiograms for each were reviewed in consensus by two experienced echocardiographers. Clinical and electrocardiographic data were obtained from chart review. RESULTS: All patients were men with class II-IV heart failure. Six had light chain CA, 1 senile CA. Six patients had coronary angiography. One had a 60% left anterior descending coronary artery stenosis. Five had nonobstructive disease. Echocardiograms for all seven patients demonstrated the distinctive pattern of preserved myocardial thickening at apex with hypokinesis in basal and midsegments. Reduced ejection fraction was present in six and increased wall thickness and myocardial echogenicity in seven. Other echo signs of amyloid were variably present. Three had low voltage on electrocardiogram. CONCLUSION: A distinctive 2D echocardiographic pattern of preserved segmental wall motion at left ventricular apex with hypokinesis in basal to midsegments was consistently identified in seven consecutive patients with endomyocardial biopsy-proven CA.

Conventional intramedullary chondrosarcoma with subarticular involvement.

A 78-year-old female patient with a lesion in the distal tibia is shown to have conventional intramedullary chondrosarcoma. Typical considerations for this end-of-bone neoplastic lesion are giant cell tumor, clear cell chondrosarcoma, and chondroblastoma. Salient clinical and radiographic features and behavior of this lesion broaden the typical view of conventional intramedullary chondrosarcoma.

Liver transplantation for hepatocellular carcinoma: defining the impact of using extended criteria liver allografts.

BACKGROUND: This series compares outcomes of patients with hepatocellular carcinoma (HCC) listed for orthotopic liver transplantation (OLT) within and outside Milan criteria, and determines the impact of extended criteria liver allografts (ECD). METHODS: Records of patients listed for liver transplantation at a single center from 1998 to 2007 were reviewed retrospectively. RESULTS: Ninety-seven HCC patients were listed for OLT, 77 underwent transplantation; 47 received ECDs and 30 standard organs. ECDs were more frequently allocated to outside Milan recipients. Wait time for OLT was shorter for outside Milan patients (4 vs. 7 months P=0.04) but hazard rate of dropout was higher (26%, 46%, and 73% at 6,12, and 24 months compared with 2%, 14%, and 60% P<0.01). Tumor size more than 3 cm (P=0.02) and model for end-stage liver disease score at listing more than 11 (P=0.04) were independent predictors of dropout. Hazard rate of OLT was similar within and outside Milan (61%, 80%, and 90% at 6, 12, and 24 months vs. 60%, 70%, and 86% P=0.38). Post-OLT survival at 1 year and 4 years were 88% and 63% within Milan compared with 79% and 62% among Milan out recipients (P=0.95). No significant post-OLT survival predictor was found. CONCLUSION: The use of ECD organs provided patients with HCCs outside Milan criteria access to liver transplant at a rate comparable to patients within Milan and model for end-stage liver disease HCC priority. Similar patient survival post-OLT can be achieved using standard or ECD organs. The higher risk of drop out in patients outside Milan, and even within Milan, with tumors more than 3 cm justifies the use of ECD organs for timely transplantation.

Recanalized umbilical vein conduit for meso-Rex bypass in extrahepatic portal vein obstruction.

BACKGROUND: Meso-Rex bypass is used to treat patients with clinically important extrahepatic portal vein obstruction (EHPVO). Usually, an autologous left internal jugular vein graft is used to bypass the portal blood circulation from the superior mesenteric vein to the left portal vein. Other vascular conduits have included the autogenous saphenous vein, splenic vein, right gastroepiploic vein, and inferior mesenteric vein. METHODS: A total of 20 umbilical veins with attached livers were harvested from 20 deceased liver donors. Umbilical veins were dilated mechanically and checked for patency and communication with the left portal vein. Vein length and diameter after dilatation were recorded. Cross-sections of 15 recanalized umbilical veins were processed by routine histologic examination and stained with hematoxylin and eosin, as well as processed by immunohistochemistry for CD31 and factor VIII antigens. Subsequently, 3 children with EHPVO underwent this modified meso-Rex bypass using the umbilical vein as a vascular conduit. RESULTS: The mean length of harvested umbilical veins was 15 cm (range, 7-21); the mean length of recanalized and usable umbilical veins was 10 cm (range, 5-15). Recanalization was successful in 16 (80%) of the 20 donor umbilical veins. The mean diameter of the umbilical veins after serial dilatation and recanalization was 1.2 cm (range, 1-2). In 11 (73%) of the 15 recanalized vein specimens, the lumen was lined by endothelial cells. In 2 children, the vascular conduit was constructed entirely with native umbilical vein. In the remaining child, 3 cm of umbilical vein was preserved and anastomosed to a mobilized inferior mesenteric vein due to inadequate length. All 3 children had patent bypass and resolution of clinical manifestations of portal hypertension at a mean follow-up of 21 months. CONCLUSION: Meso-Rex bypass may prove to be a definitive treatment for patients with EHPVO. The use of native umbilical vein as a vein conduit achieved decompression of the splanchnic venous system and should be considered a natural alternative to other interposition vein grafts.

Lung lesions in children with Crohn's disease presenting as nonresolving pneumonias and response to infliximab therapy.

Lung lesions in children with Crohn's disease are often difficult to diagnose and treat. We report here 3 children (aged 13, 14, and 17 years) on immunosuppressive therapy for previously diagnosed Crohn's disease who presented with nonresolving pneumonias. All 3 had unfavorable response to empiric antibiotics and had progression of lesions. Cultures of sputum and blood did not yield any organisms. Subsequent lung biopsies revealed noncaseating granulomas with giant cells in 2 subjects and bronchiolitis obliterans with organizing pneumonia in the third. All patients were treated with infliximab, a novel anti-tumor necrosis factor monoclonal antibody, and showed rapid clinical and radiologic response. We emphasize that a high index of suspicion for noninfectious etiologies needs to be maintained in patients with Crohn's disease who present with lung lesions to ensure timely intervention. Infliximab therapy seems to be effective and well tolerated in such patients.