Time is of the Essence: Using Extended Hemin Treatment for a Case of Severe Acute Intermittent Porphyria.

Acute intermittent porphyria (AIP) is a disorder that affects heme synthesis, leading to accumulation of upstream precursors, and can cause an array of visceral and neurological symptoms. These can be severely debilitating and even fatal if not diagnosed and treated in a timely fashion. We outline a rare case of severe AIP masquerading as ascending polyneuropathy and how it was correctly diagnosed and treated with an extended course of hemin despite initial barriers to biochemical testing for AIP.

The Diagnosis Is in the Smear: A Case and Review of Spur Cell Anemia in Cirrhosis.

The etiology of anemia in liver cirrhosis is multifactorial; one less recognized cause is hemolytic anemia due to spur cells, known as spur cell anemia. We present the case of a 57-year-old woman with alcoholic cirrhosis who presented with symptomatic macrocytic anemia with a hemoglobin level of 7.4 g/dL and signs of decompensated liver disease. Notably, she had no signs of overt bleeding. Further workup was consistent with hemolysis, with peripheral smear demonstrating spur cells. The patient was treated with both steroids and IVIG, although she eventually expired. The characteristic morphology of spur cells is due to alteration of the lipid composition of the erythrocyte membrane, changing its shape and leading to splenic sequestration and destruction. Characteristic of this disorder is an increased ratio of cholesterol to phospholipid on the membrane, as well as low levels of apolipoproteins and low- and high-density lipoproteins. The presence of spur cells is an indicator of poor prognosis and high risk of mortality. Currently, the only definitive cure is liver transplantation. There is a paucity of literature on the prevalence of this phenomenon and even less about treatment. This case highlights the importance of recognition of spur cell anemia as a cause of anemia in cirrhosis as well as the importance of the peripheral smear in the diagnostic workup. Early recognition can lead to avoidance of unnecessary procedures. Further research is needed to elucidate the true prevalence of spur cell anemia and examine further treatment options.

Complications of Intrathecal Chemotherapy in Adults: Single-Institution Experience in 109 Consecutive Patients.

Acute lymphoblastic leukemia and other aggressive lymphoid malignancies like Burkitt leukemia/lymphoma have high incidence of central nervous system (CNS) involvement. Various solid tumors, most notably breast cancer, can also metastasize into the CNS as a late stage complication causing devastating effects. Intrathecal (IT) chemotherapy consisting of methotrexate, cytarabine, or the two in combination is frequently used for the prophylaxis and treatment of CNS metastasis. Because of the high toxicity of these chemotherapeutic agents, however, their side effect profiles are potentially catastrophic. The incidence of neurotoxicity secondary to IT chemotherapy is well defined in the pediatric literature but is poorly reported in adults. Here, we investigated the incidence of neurologic and nonneurologic side effects secondary to IT chemotherapy in 109 consecutive adult patients over a two-year time period at hospitals associated with our institution. Of 355 IT chemotherapy treatments received by these patients, 11 (3.10%) resulted in paresthesias or paralysis, which we defined as significant neurologic events in our analysis. We also examined minor events that arose after IT chemotherapy, including back pain, headache, fever, vomiting, and asthenia. At least one of these occurred after 30.70% of IT chemotherapy doses. Clinicians involved in the care of patients receiving IT chemotherapy should be aware of these findings and consider treatment options lower rate of neurotoxicity such as high-dose systemic methotrexate.

Potential role of meiosis proteins in melanoma chromosomal instability.

Melanomas demonstrate chromosomal instability (CIN). In fact, CIN can be used to differentiate melanoma from benign nevi. The exact molecular mechanisms that drive CIN in melanoma have yet to be fully elucidated. Cancer/testis antigens are a unique group of germ cell proteins that are found to be primarily expressed in melanoma as compared to benign nevi. The abnormal expression of these germ cell proteins, normally expected only in the testis and ovaries, in somatic cells may lead to interference with normal cellular pathways. Germ cell proteins that may be particularly critical in CIN are meiosis proteins. Here, we review pathways unique to meiosis with a focus on how the aberrant expression of meiosis proteins in normal mitotic cells "meiomitosis" could impact chromosomal instability in melanoma and other cancers.

Germ cell proteins in melanoma: prognosis, diagnosis, treatment, and theories on expression.

Germ cell protein expression in melanoma has been shown to correlate with malignancy, severity of disease and to serve as an immunologic target for therapy. However, very little is known about the role that germ cell proteins play in cancer development. Unique germ cell pathways include those involved in immortalization, genetic evolution, and energy metabolism. There is an ever increasing recognition that within tumors there is a subpopulation of cells with stem-cell-like characteristics that play a role in driving tumorgenesis. Stem cell and germ cell biology is intertwined. Given the enormous potential and known expression of germ cell proteins in melanoma, it is possible that they represent a largely untapped resource that may play a fundamental role in tumor development and progression. The purpose of this paper is to provide an update on the current value of germ cell protein expression in melanoma diagnosis, prognosis, and therapy, as well as to review critical germ cell pathways and discuss the potential roles these pathways may play in malignant transformation.

Diagnostic role of chromosomal instability in melanoma.

Early diagnosis gives melanoma patients the best chance for long term survival. However discrimination of an early melanoma from an unusual/atypical benign nevus can represent a significant challenge. There are no current pathological markers to definitively define malignant potential in these indeterminate lesions. Thus, there is a need for improved diagnostic tools. Chromosomal instability (CIN) is a hallmark of cancer and is markedly prevalent in melanoma. Advances in genomics have opened the door for the development of molecular tools to better segregate benign and malignant lesions. This paper focuses on CIN in melanoma and the role of current diagnostic approaches.