Alexander C. Black

The reliability of fine-needle aspiration biopsy as the initial diagnostic procedure for palpable masses: a 4-year experience of 730 patients from a community hospital-based outpatient aspiration biopsy clinic.

Fine‐needle aspiration biopsy (FNAB) is a reliable, rapid, minimally invasive alternative to surgical biopsy when it is performed by physician specialists for the diagnosis of palpable masses. FNAB may be under‐utilized in community hospitals in the U.S. because physicians without specialty training commonly provide the service, resulting in less reliable results.

Specific binding of polypyrimidine tract binding protein and hnRNP A1 to HIV-1 CRS elements

The human immunodeficiency virus (HIV) Rev and human T-cell leukemia virus (HTLV) Rex proteins regulate viral RNA processing. Both proteins act to overcome the block to viral structural gene expression, at least in part, by reversing the inhibitory effect of intronic RNA sequences, termed cis-acting repressive (CRS) sequences. Using HTLV type II (HTLV-II) as a model, we recently showed that the function of a 5′ long terminal repeat (LTR) CRS correlates with in vitro binding by both polypyrimidine tract binding (PTB) protein (also known as hnRNP I) and hnRNP A1 to CRS RNA (1,2). Using radioimmunoprecipitation of proteins ultraviolet (UV) crosslinked to each HIV CRS RNA with monoclonal anti-hnRNP antibodies, we now demonstrate that hnRNP I and hnRNP A1 bind to two different HIV-1 CRS RNAs. In addition, we show that hnRNP I and hnRNP A1 binding to HIV-1 CRS RNAs can be specifically competed by HTLV-II CRS RNAs using electrophoretic mobility shift assay (EMSA)/UV crosslinking assays. Binding by both hnRNP I and hnRNP A1 to HIV-1 and HTLV-II CRS RNAs suggests a role for these proteins in CRS function that may be influenced by the Rev and Rex proteins, respectively.

Breast‐Conservation Treatment Outcomes: A Community Hospital’s Experience

Abstract:  In the United States, the majority of early breast cancer patients choose breast‐conserving treatment in the community setting, yet there is a paucity of literature describing outcomes. In this paper, we describe our experience with breast‐conserving treatment in a small community hospital. Our hospital tumor registry was used to identify breast cancer cases diagnosed at our hospital between 1997 and 2003. We limited our study to those women with initial attempts at breast‐conserving surgery (BCS) who had follow‐up oncology treatment at on‐campus affiliated oncological services. We looked at factors that influence survival for early stage 0–II disease such as tumor and patient characteristics, completeness of local surgical tumor excision, and adjuvant treatment. We also evaluated the percentage of cases in which the initial BCS did not achieve adequate surgical oncological results and the number and type of subsequent surgeries that were required to achieve this goal. There were 185 cases with a median patient age of 55 and a median follow‐up time of 53 months. Most tumors were stage 0–I (68%) or stage II (23%). A single surgery was deemed sufficient to achieve the desired oncological outcome in 54% of cases; the remaining cases (46%) required additional surgeries. A final margin of 5 mm or greater was successfully achieved in 81% of cases. Ninety‐two percent of the patients underwent radiotherapy, 65% received hormonal therapy, and 49% underwent chemotherapy. One hundred and sixty one patients had successful breast‐conserving surgeries (87%) and 24 patients (13%) ultimately required mastectomy. There were four loco‐regional recurrences and 19 deaths during the study period. Our disease‐free survival rate for early‐stage cancer (stage 0–II) was 91% at 5 years. Our study shows that high‐quality patient outcomes for breast‐conserving treatment can be achieved in the community setting.

Myelopathy after radiation therapy and chemotherapy with capecitabine and gemcitabine.

This article describes a woman with metastatic upper gastrointestinal cancer who developed thoracic myelopathy unexpectedly after standard dosage and fractionation radiotherapy. She also was receiving capecitabine and gemcitabine concomitantly. There are few reported cases of chemotherapy potentiation of spinal cord radiation toxicity. These agents are known radiosensitizers, making it likely that they contributed to this adverse outcome. As these agents are increasingly incorporated into clinical trials of combined therapy, caution will be necessary in both trial design and clinical management.

Intra-Articular Metastatic Pancreatic Carcinoma of the Right Knee Mimicking Septic Arthritis

Recent multiagent chemotherapy regimens have increased overall survival in patients with metastatic pancreatic cancer. Common toxicities of these regimens include nausea, fatigue, diarrhea, skin rashes, peripheral neuropathy, and myelosuppression with increased incidence of infections. Pancreatic cancer tends to spread to adjacent anatomic tissues, regional lymph nodes, liver, lung, and, less commonly, bone cortex and brain. Metastases to other sites, in particular to joint synovium, are extremely rare. Only a small number of cases of cancer metastasizing to joint have been reported. We present a case of an otherwise healthy middleaged man with advanced pancreatic cancer who, after several multiagent cancer treatments, developed sudden right knee swelling and pain. Although the initial clinical impression was septic arthritis, cytologic analysis confirmed metastatic pancreatic cancer. He experienced symptomatic relief with joint aspiration and radiation, but succumbed shortly thereafter to progressive disease. As patients survive longer with more effective treatment of pancreatic cancer, there is an increased chance of unusual sites of metastases, as is illustrated by this case.

Constitutive Expression of the HTLV-I pX and env Regions in Jurkat T-cells Induces Differential Activation of SRE, CRE and NFκB Pathways

Human T-cell leukemia virus type I (HTLV-I) causes adult T-cell leukemia/lymphoma (ATLL). HTLV Tax, the viral transcriptional activator, can activate a variety of cellular genes. HTLV-mediated T-cell transformation, however, may involve additional viral proteins expressed from singly- as well as doubly-spliced viral mRNA. To determine the combined effect of these viral proteins on cellular gene expression in Jurkat T-cells, we derived stable transfectants that constitutively express the HTLV-I pX and env regions (J3.9). J3.9 cells show substantially increased mRNA levels of egr-1 and c-jun but no induction of either CD25 or GM-CSF by Northern blotting. This pattern corresponded to the activation of an egr-1 but not a GM-CSF promoter-driven reporter construct in transient gene expression assays. In DNA electrophoretic mobility shift assays (EMSA), nuclear extract from J3.9 cells has significantly increased binding to CRE and SRE but not nuclear factor kappa B (NFκB) DNA oligos, as compared to J-Neo cell extract. These results suggest that low level expression of pX and env region gene products in Jurkat T-cells stimulates persistent activation of CRE- and SRE- but not NFκB-induced cellular genes.