Targeting the anterior superior iliac spine yields significantly longer bone marrow cores.

Pathologists and haematologists generally agree that the length of the biopsy core is a good surrogate for the diagnostic quality of the bone marrow. Previous studies suggested that the angulation of the biopsy needle from the posterior superior iliac spine (PSIS) could influence the length of the biopsy cores, targeting the anterior superior iliac spine (ASIS) from the PSIS would yield longer specimens than the traditional angulation technique (TAT), where the biopsy needle is directed straight in, perpendicular to the plane of the back. Twenty five adult haematology patients were prospectively recruited by haematologists-in-training (HITs), who were trained to target the ASIS using a lateral angulationtechnique (LAT). The mean length of biopsy cores was 16 mm and that was significantly longer (p=0.003) than a comparable group of bone marrow biopsies previously obtained by HITs using the TAT approach. These results support the LAT as a new standard of haematology practice. TRIAL REGISTRATION NUMBER: NCT 02524613.

Primary Hepatic Small Cell Carcinoma: Two Case Reports, Molecular Characterization and Pooled Analysis of Known Clinical Data.

Primary hepatic small cell carcinoma (HSCC) is a rare malignancy that has previously been described in only few case reports. The clinicopathological course, natural history, molecular markers and ideal treatment strategy for this tumor have not been fully elucidated. Herein, we report on two cases of spontaneously arising, metastatic primary HSCC that were treated at our Institution. Both patients succumbed to their disease within two months of initial presentation. Both cases underwent postmortem examination and no evidence of a pulmonary or other non-hepatic small cell primary was found. Unlike pulmonary small cell tumors, these two hepatic primaries showed only locoregional spread and very few distant metastases. Formalin-fixed samples were obtained at autopsy and sequenced using single-nucleotide polymorphism arrays and whole-genome sequencing. Four mutations in the epidermal growth factor receptor (EGFR) gene known to be associated with response to tyrosine kinase inhibitors (TKIs) were detected in one of the two HSCC samples. A systematic review and pooled analysis of all previously reported cases of primary HSCCs was conducted. The median overall survival was estimated at 4 months. Surgical resection was significantly associated with longer overall survival (hazard ratio =0.13, 95% confidence interval=0.03-0.69). Although several case reports of primary HSCC have been reported prior to this publication, to our knowledge this is the first time that molecular and systematic analysis has been conducted in order to more fully characterize this rare disease. Our results indicate that surgical resection, when feasible, may be a valid option in primary HSCC, and that some tumors may respond to TKIs against EGFR.

More than a headache: a case of cetuximab-induced aseptic meningitis.

While the wide belief is that monoclonal antibodies, due to their large size, would not be able to penetrate the blood-brain barrier, we present a rare case of aseptic meningitis induced by intravenous cetuximab administration. A 58-year-old man with tonsillar squamous cell cancer presented with headache and fever, which started approximately 1 h after his first dose of cetuximab (loading dose of 400 mg/m(2) equalling 800 mg). CT scan of the head was non-revealing and laboratory tests including complete blood count, serum comprehensive metabolic panel and coagulation profile were within normal limits. Aseptic meningitis in the setting of cetuximab therapy has been reported on 6 previous occasions. Consistent with these prior reports, it is interesting to note that this case also occurred after administration of the initial higher loading dose of Cetuximab. This is of interest as Cetuximab is more frequently being dosed at 500 mg/m(2) (higher dose) every 2 weeks in colorectal cancer.

A rare cause of acquired immune deficiency syndrome related pancytopenia.

A 21-year-old male with acquired immune deficiency syndrome, not on highly active antiretroviral treatment (HAART) was admitted after complaining of headache and intermittent diarrhea, found to have Cryptococcal meningitis. During the course of his hospitalization, patient developed pancytopenia. Anemia panel, serologies including Epstein barr virus, cytomegalovirus, and parvovirus were negative. Patient then developed high grade fever with elevated liver enzymes. Blood cultures, urine cultures, stool cultures, and repeat cerebrospinal fluid cultures remained negative. Patient subsequently developed skin lesions which on biopsy showed Kaposi's sarcoma, and upon endoscopy, noted to have gastrointestinal Kaposi's sarcoma involvement. Human herpes virus 8 was positive. Bone marrow biopsy revealed hemophagocytic lymphohistiocytosis. Despite having a concern for patient developing immune reconstitution syndrome which may worsen his meningitis, HAART was initiated and patient's symptoms improved including resolution of fevers and hematological as well as liver abnormalities. Kaposi's sarcoma improved as well.

Acquired Von Willebrand's Syndrome in Systemic Lupus Erythematosus.

Acquired von Willebrand syndrome (AVWS) is an uncommon, underdiagnosed, and heterogeneous disease which is increasingly recognized as a cause of bleeding diatheses. Systemic lupus erythematosus (SLE) is an infrequent cause of AVWS. Herein, we report a case of AVWS diagnosed during the initial presentation of SLE in a previously healthy young man with no family history of bleeding diathesis who presented with worsening epistaxis, gastrointestinal bleeding, and anasarca. He was found to have severe anemia and prolonged activated partial thromboplastin time (aPTT) with severely decreased levels of von Willebrand factor (VWF) measurements in addition to markedly decreased factor VIII levels. Further evaluation revealed nephrotic syndrome and interstitial lung disease due to SLE. He initially received combination therapy with intravenous immunoglobulin (IVIG) and von Willebrand factor/factor VIII concentrates without significant improvement. Treatment with steroids, cyclophosphamide, and rituximab was followed by clinical improvement evidenced by cessation of bleeding. The short follow-up did not allow us to definitely prove the therapeutic effect of immunosuppressive treatment on AVWS in SLE patients. This case adds to the literature supporting the relationship between AVWS and SLE and highlights the importance of combination therapy in the treatment of severe AVWS as well as the role of IVIG, cyclophosphamide, and rituximab in AVWS associated with SLE.

36-year-old female with catastrophic antiphospholipid syndrome treated with eculizumab: a case report and review of literature.

Catastrophic antiphospholipid syndrome (CAPS) is a rare but potentially life-threatening condition characterized by diffuse vascular thrombosis, leading to multiple organ failure developing over a short period of time in the presence of positive antiphospholipid antibodies (aPL). CAPS is a severe form of antiphospholipid syndrome, developing in about 1% of cases of classic antiphospholipid syndrome, manifesting as microangiopathy, affecting small vessels of multiple organs. It is acute in onset, with majority of cases developing thrombocytopenia and less frequently hemolytic anemia and disseminated intravascular coagulation. Lupus anticoagulant and anticardiolipin antibodies have been reported as predominant antibodies associated with CAPS. Treatment options often utilized in CAPS include anticoagulation, steroids, plasma exchange, cyclophosphamide therapy, and intravenous immunoglobulin therapy. Even though the reported incidence of this condition is considered to be low, the mortality rate is approaching 50%. The high rate of mortality should warrant greater awareness among clinicians for timely diagnosis and treatment of this life-threatening condition. Studies have shown that complement activation plays a key role in the pathogenesis of aPL mediated thrombosis in CAPS. We report a case of a 36-year-old female admitted with clinical and laboratory findings consistent with CAPS successfully treated with eculizumab, a terminal complement inhibitor.

Unusual cause of cholestatic jaundice in a patient with AIDS.

A 61-year-old man with AIDS on chronic highly active antiretroviral treatment (HAART) presented with lethargy and jaundice and was found to have abnormal liver function tests (LFTs). Investigations including viral/autoimmune markers and imaging were unrevealing, except for positive Epstein-Barr virus. HAART was held, however, transaminases and total bilirubin continued to rise. The liver biopsy revealed classical Hodgkin's lymphoma (HL). HL presenting only with liver findings without lymphadenopathy is rare. Extreme cases can lead to fulminant liver failure. The bone marrow biopsy and dramatic elevation in serum ferritin were consistent with haemophagocytic lymphohistiocytosis. Finding a chemotherapy regimen was challenging given abnormal LFTs and HAART interactions. Initial chemotherapy regimen has successfully decreased LFTs; however, it was limited by pancytopenia. The patient's regimen was changed, however second regimen was complicated by neuropathy. LFTs improved and the patient was able to receive the standard care chemotherapy for HL with significant clinical, laboratory and radiological improvement.

The OnControl bone marrow biopsy technique is superior to the standard manual technique for hematologists-in-training: a prospective, randomized comparison.

The purpose of this study was to compare a novel bone marrow device with the standard marrow needle in a prospective, randomized study in a teaching hospital employing hematologists-in-training. The new device, the OnControl Bone Marrow (OBM) Biopsy System, utilizes a battery-powered drill to insert the needle. Fifty-four bone marrows (27 standard and 27 OBM) were performed by 11 fellows under the observation and supervision of 3 attending hematologists and 1 research technologist. The primary endpoint of the study, the mean length of the marrow biopsy specimens, a surrogate for marrow quality, was determined by a pathologist in a blinded manner. The mean length of the marrow biopsy specimens was significantly longer (56%) for the OBM group (15.3 mm) than for the standard bone marrow (SBM) group (9.8 mm), P<0.003. An objectively determined secondary endpoint; mean procedure time, skin-to-skin; also favored the OBM group (175 s) versus the SBM group (292 s), P<0.007. Several subjective secondary endpoints also favored the OBM group. Only minor adverse events were encountered in the OBM and SBM study groups. It was concluded that bone marrow procedures (BMPs) performed by hematologists-in-training were significantly faster and superior in quality when performed with the OBM compared to the SBM. These data suggest that the OBM may be considered a new standard of care for adult hematology patients. OBM also appears to be a superior method for training hematology fellows.

Need for inferior vena cava filters in cancer patients: a surrogate marker for poor outcome.

BACKGROUND: Cancer patients have an increased incidence of venous thromboembolism (VTE). Inferior vena cava (IVC) filters are used extensively in the US, and more than 40 000 are inserted annually. The impact on survival of cancer patients receiving IVC filters has not been studied. METHODS: A retrospective study examined 206 consecutive cancer patients with VTE to compare the effects of IVC filter placement with anticoagulation (AC) therapy on overall survival (OS), as measured from the time of VTE. Patients were classified into 3 treatment groups: AC (n = 62), IVC filter (77), or combination IVC filter + AC (67). RESULTS: Treatment groups did not differ with respect to age, sex, or albumin levels. Median OS was significantly greater in patients treated with AC (13 months) compared with those treated with IVC filters (2 months) or IVC + AC (3.25 months; P < .0002). IVC patients were 1.9 times more at risk of death than AC only (hazard ratio = .528; 95% confidence interval = .374 to .745). Multivariate analysis revealed that performance status and type of thrombus were not confounders and had no effect on OS. CONCLUSION: The need for the insertion of an IVC filter projected markedly reduced survival. Patients requiring an IVC filter rather than AC as initial therapy face a 2-fold increase in risk of death. Whether or not this therapeutic procedure has a positive impact on outcome in cancer patients is uncertain. Complications resulting from thrombosis were also analyzed in this cohort. A prospective randomized trial at our institution is addressing this issue.