Budd-Chiari syndrome treated with direct intrahepatic portocaval shunt: A case report.

Budd-Chiari syndrome is an uncommon disorder characterized by occlusion of hepatic veins. It can lead to portal hypertension. Most common causes of this syndrome are hypercoagulability states. Transjugular intrahepatic portosystemic shunt is often not possible given the portal venous thrombosis. In these cases, direct intrahepatic portocaval shunt, involving the creation of an access between the portal vein and the systemic circulation via the intrahepatic inferior vena cava has proven to be a feasible alternative, and can improve portal hypertension in these patients. Herein, we present a case of a 37-year-old woman diagnosed with Budd-Chiari syndrome that was successfully treated with percutaneous ultrasound (US)-guided direct intrahepatic portocaval shunt.

Meckel's diverticulum: Unusual cause of significant bleeding in an adult male.

Meckel's diverticulum is a common congenital gastrointestinal malformation affecting 2% of the general population. Most affected patients are asymptomatic, and excessive bleeding causing a significant drop in hemoglobin count is an uncommon complication of Meckel's diverticulum, especially in adult patients. Herein, we present an adult case of Meckel's diverticulum that nearly led to hemodynamic instability. Laparotomy and segmental small bowel resection were critical in treating the patient.

Incidental diagnosis of sternoclavicular septic arthritis with Moraxella nonliquefaciens.

An 83-year old man presented acutely to the emergency department with generalized weakness and subjective fevers. A month earlier he had undergone resection of a large intramuscular sarcoma from his thigh. The cancer staging work-up was still underway and a decision about adjuvant therapy was still pending. Although initial laboratory assessment showed leukocytosis, this normalized soon after admission without the use of antimicrobials. No fevers were documented. During the admission an 18F-FDG PET/CT was performed in continuation of his sarcoma staging workup. This revealed unexpected abnormal radiotracer uptake in the left sternoclavicular joint with fluid collections extending into the sternocleidomastoid muscle and the mediastinum. Imaging findings were consistent with septic arthritis and abscess formation, despite lack of fever or localizing symptoms. Ultrasound-guided aspiration revealed purulent fluid that grew Moraxella nonliquefaciens. Given the unusual presentation, ongoing clinical uncertainty about the true cause of the septic joint, and concern for an occult sarcoma metastasis, surgical debridement and resection of the joint was carried out. Pathology and microbiology evaluation confirmed septic arthritis with osteomyelitis and abscess extension into the mediastinum. No tumor cells were identified. Postoperative course was complicated by hematoma, but otherwise the patient responded well to antimicrobial therapy.

Posterior Reversible Encephalopathy Syndrome on 18F-FDG PET/CT in a Pediatric Patient With Burkitt's Lymphoma.

We present a case of posterior reversible encephalopathy syndrome (PRES) in a pediatric patient with Burkitt's lymphoma predominantly involving the bone marrow. F-FDG PET/CT scan obtained after the first cycle of chemotherapy, complicated by acute kidney injury, hypertension, tumor lysis syndrome, and lethargy with focal neurological symptoms, showed a favorable marrow and lymph node response but increased FDG uptake in the bilateral frontal and occipital cortical/subcortical regions. Brain MRI was consistent with PRES. The patient was managed with IV hydration and blood pressure control with symptom resolution. This case shows the F-FDG uptake pattern of PRES in postchemotherapy setting.

Genetic Syndromes Associated with Central Nervous System Tumors.

Several genetic tumor syndromes have associated central nervous system (CNS) neoplasms. The spectrum of syndromes that have intracranial tumor manifestations includes ataxia telangiectasia, Cowden syndrome, familial adenomatous polyposis, hereditary non-polyposis-related colorectal cancer, Li-Fraumeni syndrome, Gorlin syndrome, neurofibromatosis types 1 and 2, multiple endocrine neoplasia type 1, tuberous sclerosis complex, von Hippel-Lindau disease, and Turcot syndrome. Many of these disorders are inherited in an autosomal dominant fashion, and identification of the associated genetic defects has led to improved understanding of the molecular pathways involved in tumorigenesis, helping pave the way to the emergence of molecularly targeted therapeutics. Recognition of individuals and families at risk for such tumors is critical to improve clinical care and optimize proper genetic counseling. To contribute effectively, the radiologist should recognize the common varieties of tumors and characteristic neuroimaging manifestations seen in each familial syndrome. A fundamental understanding of the genetics and molecular pathogenesis of these tumors is critical in understanding the development of specific and unique tumors in each entity. In this article, we review the most common genetic tumor syndromes with associated intracranial neoplasms, with emphasis on recent genetic and molecular biology data, clinical manifestations, and management as well as the controversies and current recommendations for screening and surveillance. A detailed overview of all the major and pertinent CNS imaging features will be elucidated, including computed tomography, magnetic resonance imaging, and, in relevant cases, magnetic resonance spectroscopy. ©RSNA, 2016.

Association between CLN3 (Neuronal Ceroid Lipofuscinosis, CLN3 Type) Gene Expression and Clinical Characteristics of Breast Cancer Patients.

Breast cancer is the most common cancer in women worldwide. Elucidation of underlying biology and molecular pathways is necessary for improving therapeutic options and clinical outcomes. CLN3 protein (CLN3p), deficient in neurodegenerative CLN3 disease is anti-apoptotic, and defects in the CLN3 gene cause accelerated apoptosis of neurons in CLN3 disease and up-regulation of ceramide. Dysregulated apoptotic pathways are often implicated in the development of the oncogenic phenotype. Predictably, CLN3 mRNA expression and CLN3 protein were up-regulated in a number of human and murine breast cancer-cell lines. Here, we determine CLN3 expression in non-tumor vs. tumor samples from fresh and formalin-fixed/paraffin-embedded (FFPE) breast tissue and analyze the association between CLN3 overexpression and different clinicopathological characteristics of breast cancer patients. Additionally, gene expression of 28 enzymes involved in sphingolipid metabolism was determined. CLN3 mRNA is overexpressed in tumor vs. non-tumor breast tissue from FFPE and fresh samples, as well as in mouse MCF7 breast cancer compared to MCF10A normal cells. Of the clinicopathological characteristics of tumor grade, age, menopause status, estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2), only absence of HER2 expression correlated with CLN3 overexpression. Sphingolipid genes for ceramide synthases 2 and 6 (CerS2; CerS6), delta(4)-desaturase sphingolipid 2 (DEGS2), and acidic sphingomyelinase (SMPD1) displayed higher expression levels in breast cancer vs. control tissue, whereas ceramide galactosyltransferase (UGT8) was underexpressed in breast cancer samples. CLN3 may be a novel molecular target for cancer drug discovery with the goal of modulation of ceramide pathways.

The clinical use of DNA methyltransferase inhibitors in myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) include a heterogeneous group of acquired hematopoietic malignancies characterized by ineffective hematopoiesis, peripheral cytopenias, and a varying propensity for progression to acute myeloid leukemia. Patients with higher risk MDS have dismal outcomes and treatment options are very limited. Aside from allogeneic hematopoietic cell transplantation, the only potentially curative treatment, DNA methyltransferase inhibitors (DNMTIs) are the only intervention that prolongs overall survival in patients with higher risk MDS. The clinical use of DNMTIs in MDS was one of the earliest successful attempts at epigenetic reprogramming of cancer. In this review, we discuss the clinical use of DNMTIs in MDS highlighting the current challenges and controversies and future directions of research needed to explore the full therapeutic potential of these agents.

Clinical utility of lenalidomide in the treatment of myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) represent a heterogeneous group of acquired clonal hematopoietic disorders characterized by peripheral blood cytopenias, paradoxical BM hypercellularity, ineffective hematopoiesis, and increased risk of leukemic transformation. Risk stratification, using different prognostic scores and markers, is at the core of MDS management. Deletion 5q [del(5q)] MDS is a distinct class of MDS characterized by the haploinsufficiency of specific genes, microRNAs, and proteins, which has been linked to increased sensitivity to the drug lenalidomide. Phase II and III clinical trials have demonstrated the efficacy of lenalidomide in improving clinical outcomes of patients with del(5q) MDS, including reduction in red blood cell transfusion requirements and improvements in quality of life. Lenalidomide has also demonstrated some activity in non-del(5q) lower-risk MDS as well as higher-risk MDS, especially in combination with other agents. In this paper, we review the pathogenesis of del(5q) MDS, the proposed mechanisms of action of lenalidomide, the major clinical trials that documented the activity of lenalidomide in different MDS populations, potential predictors of benefit from the drug and suggested mechanisms of resistance, and the use of combination strategies to expand the clinical utility of lenalidomide in MDS.

Risk stratification in myelodysplastic syndromes: is there a role for gene expression profiling?

Evaluation of: Pellagatti A, Benner A, Mills KI et al. Identification of gene expression-based prognostic markers in the hematopoietic stem cells of patients with myelodysplastic syndromes. J. Clin. Oncol. 31(28), 3557-3564 (2013). Patients with myelodysplastic syndromes (MDS) exhibit wide heterogeneity in clinical outcomes making accurate risk-stratification an integral part of the risk-adaptive management paradigm. Current prognostic schemes for MDS rely on clinicopathological parameters. Despite the increasing knowledge of the genetic landscape of MDS and the prognostic impact of many newly discovered molecular aberrations, none to date has been incorporated formally into the major risk models. Efforts are ongoing to use data generated from genome-wide high-throughput techniques to improve the 'individualized' outcome prediction for patients. We here discuss an important paper in which gene expression profiling (GEP) technology was applied to marrow CD34(+) cells from 125 MDS patients to generate and validate a standardized GEP-based prognostic signature.

Changing frequency of equivocal HER-2/neu scores and factors predictive of negative HER 2/neu fluorescent in situ hybridisation in invasive carcinomas of the breast.

BACKGROUND: Analysis of human epidermal growth factor receptor 2 (HER-2) status has become standard of care in breast cancer patients due to its important prognostic and therapeutic implications. Immunohistochemistry (IHC) is the most commonly used primary method for detection of HER-2 overexpression. Controversy exists on the interpretation of samples that are equivocal for HER 2 status (IHC 2+). Recent guidelines state that samples equivocal for HER 2 status require validation with fluorescent in situ hybridisation (FISH). The use of FISH, however, despite higher accuracy comes at a higher cost that is not affordable to all patients. METHODS: This study is a retrospective study conducted at the American University of Beirut Medical Center, including women diagnosed with breast cancer with equivocal IHC scores presenting between 2009 and 2011. We attempted to correlate clinicopathological characteristics of patients diagnosed with breast cancer that can influence conclusions made on HER 2 status when analysing IHC equivocal samples in an effort to decrease the need for FISH testing. 113 patients in our records were included; charts were reviewed for different patient clinical characteristics and samples were analysed for pathological characteristics. RESULTS: Using logistic regression, progesterone receptor status and HER-2 staining of the normal glands around the tumour by IHC were the two statistically significant variables that showed association with FISH results. The strength of progesterone receptor status positivity and HER-2 staining of the normal glands around the tumour were proportional to the likelihood of a negative FISH. Also, the presence of strong and diffuse hormone receptor positivity in low-grade tumours was predictive of negative HER-2 status. CONCLUSIONS: In countries where resources are strained, oncologists need to think of measures to minimise the increasing financial burden of cancer care. Our study serves to highlight a few clinicopathological characteristics that might eliminate the need for further testing through FISH.

Histoplasma epiglottitis in a patient with Crohn's disease maintained on infliximab, prednisone, and azathioprine.

Crohn's disease is associated with treatment and non-treatment infectious complications. Among the treatment-related infectious complications, Histoplasma infection is interesting because of significant overlap between its symptoms and Crohn's disease exacerbation. It is often mistaken as Crohn's disease exacerbation. We present a case of disseminated histoplasmosis presenting as Histoplasma epiglottitis in a patient with Crohn's disease maintained on infliximab, prednisone, and azathioprine.

Seronegative antiphospholipid syndrome.

APS is an autoimmune disease that leads to arterial and/or venous thrombosis, recurrent pregnancy loss and persistently positive aPLs. Patients with clinical manifestations highly suggestive of APS but persistently negative conventional aPLs are classified as having seronegative APS. Ongoing research has revealed the existence of non-criteria antibodies proposed to be relevant to APS and that can be potentially included in the disease's classification criteria. We present a literature review on the most promising antibodies of this heterogeneous aPL family, which includes antibodies to a zwitterionic phospholipid, namely phosphatidylethanolamine, phospholipid-binding plasma proteins, phospholipid-protein complexes and anionic phospholipids other than cardiolipin. Although these molecules can increase the diagnostic yield of APS, their clinical relevance is still debatable and needs to be confirmed by interlaboratory efforts toward standardizing diagnostic tools, in addition to experimental data and larger longitudinal studies.

Review article: late post-hysterectomy ectopic pregnancy.

Ectopic pregnancy after hysterectomy is a rare but potentially life-threatening condition requiring prompt diagnosis to prevent the increased mortality associated with rupture. Twenty-seven cases of late post-hysterectomy ectopic pregnancy reported in the English literature since 1918 were reviewed and analysed for presenting symptoms, missed diagnosis rate at initial presentation, location of ectopic and rupture rate at diagnosis. The presenting symptoms were found to be non-specific. The diagnosis in this population is twice more likely to be missed than in women with intact uteri. The rupture rate is 63%, compared with 37% in women with intact uteri. The majority of late post-hysterectomy ectopic pregnancies (62%) were located in the fallopian tubes. Because of the potential risk of mortality, emergency physicians should always consider the possibility of ectopic pregnancy in childbearing women whose surgical history includes hysterectomy without oophorectomy. Evaluation of abdominal pain in this population should include a pregnancy test to ensure prompt diagnosis when the possibility of pregnancy exists clinically.

Gastric antral vascular ectasia in a patient with GIST after treatment with imatinib: case report and literature review.

Imatinib mesylate is a receptor kinase inhibitor approved by the Food and Drug Administration for the treatment of malignant metastatic and/or unresectable gastrointestinal stromal tumors and chronic myelogenous leukemia. Although imatinib is generally well tolerated, certain adverse drug reactions are common. These include gastrointestinal side-effects such as diarrhea, nausea and vomiting, as well as hematological side-effects and other miscellaneous side-effects such as fatigue, edema, dermatitis and dyspnea. We present a previously unreported adverse effect of imatinib, gastric antral vascular ectasia, in a 74-year-old woman with gastrointestinal stromal tumor in remission treated with adjuvant imatinib. Endoscopy performed prior to starting imatinib showed normal gastric mucosa, but 8 months after starting imatinib showed diffuse gastric inflammation. Repeat endoscopy 1 month after discontinuing imatinib showed significant improvement in gastric inflammation.