Safe and successful bone marrow biopsy: an anatomical and CT-based cadaver study.

Bone marrow biopsy is generally a safe procedure. However, infrequently the procedure is associated with serious injuries that are attributed to inadvertent needle penetration of the iliac bone's inner cortex. An evidence-based approach to needle orientation during iliac crest biopsy does not exist. In our study, the posterior to anterior path of the bone marrow needle from the posterior superior iliac spine (PSIS) was studied in human cadavers in two orientations: (1) perpendicularly to the coronal plane (the perpendicular approach) and (2) laterally toward the ipsilateral anterior superior iliac spine (ASIS) (the lateral approach). The biopsy needle was deliberately advanced through the inner ilial cortex in both approaches. Dissections and imaging studies were done to identify the relationship of the penetrating needle to internal structures. Both approaches begin with a perpendicular puncture of the outer cortex at the PSIS. The perpendicular approach proceeds anteriorly whereas in the lateral approach the needle is reoriented toward the ipsilateral ASIS before advancing. The lateral approach caused less damage to neurovascular structures and avoided the sacroiliac joint compared to the perpendicular approach. This procedure is best done in the lateral decubitus position. Proper use of the lateral approach should obviate many of the complications reported in the literature.

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.

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.

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.