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Prostate Cancer Prevention: Strategies and Realities

Introduction Prostate cancer is the most commonly diagnosed male malignancy in the United States with approximately 230,000 patients diagnosed each year. Worldwide, about 900,000 men are diagnosed annually, making prostate cancer a global public health problem. In the era of prostate-specific antigen (PSA) screening, most men are now diagnosed with clinically localized prostate cancer and face difficult treatment decisions due to the protracted history of the…

Imaging in Localized Prostate Cancer

Introduction Prostate cancer affects one in seven men in the United States, and it is estimated that 12% of affected men will die from their disease. Prostate cancer represents a spectrum of disease ranging from indolent with a low risk of mortality to very aggressive with a high risk of metastases leading to death. For most patients, prostate cancer will not be the cause of death…

Total and Free PSA, PCA3, PSA Density and Velocity

Introduction Since the late 1980s, the diagnosis and follow-up of prostate cancer (PCa) has relied on the use of prostate-specific antigen (PSA), a blood laboratory measurement that was shown to be associated with pathological diagnosis of cancer and had both diagnostic and prognostic clinical validity and utility. In 1986 the Food and Drug Administration approved the test to monitor those men already diagnosed with cancer, and…

Biopsy Prophylaxis, Technique, Complications, and Repeat Biopsies

Biopsy prophylaxis The majority of prostate biopsies are performed with transrectal ultrasound (TRUS) guidance and tissue sampling, with only a small proportion being done via a transperineal approach. The bacterial colonization of the rectum with gram-negative organisms poses a significant and potentially devastating risk of infection and sepsis during TRUS biopsy. Rates of sepsis after prostate biopsy have been traditionally reported to be 1–3%. Risk factors…

Prostate Cancer and Other Primary Malignancies

Background As the detection and treatment of cancer improve, the prevalence of multiple primary malignancies has increased and will undoubtedly continue to increase. One out of every two men will receive a cancer diagnosis in their lifetime, with prostate cancer comprising 44% of these diagnoses. According to the Surveillance, Epidemiology, and End Results (SEER) Program database, as of 2013, 16% of new cancer diagnoses represented a…

Prostate Cancer in the Elderly

Introduction Prostate cancer is a disease of the elderly, with the peak incidence of diagnosed disease at 80 years of age. While many view prostate cancer as an indolent disease, it still remains the second leading cause of cancer death among men in the United States, second only to lung cancer. Men aged ≥75 at diagnosis account for over 50% of prostate cancer deaths and almost…

High Grade Prostatic Intraepithelial Neoplasia and Atypical Glands

Introduction High-grade prostatic intraepithelial neoplasia (HGPIN) and atypical small acinar proliferation (ASAP) are intermediaries to distinctly benign or malignant diagnoses on prostate biopsy. HGPIN is a true pathologic entity and the only accepted precursor to prostate adenocarcinoma. ASAP on the other hand is not a defined pathologic entity, but instead represents diagnostic ambiguity with atypical findings suspicious but not sufficient for a diagnosis of malignancy. Given…

Should Gleason Score 6 Still Be Called Cancer?

Introduction While the lifetime risk of a prostate cancer diagnosis for a man living the United States is estimated to be 1 in 7, the incidence to mortality ratio is nearly 8:1. Thus, most men diagnosed with prostate cancer will not die of the disease. The era of prostate-specific antigen (PSA) screening has resulted in the diagnosis of lower grade and volume cancers. While PSA screening…

Novel Research on Fusion Genes and Next-Generation Sequencing

Recurrent translocations in prostate cancer Discovery of Recurrent Translocations in Prostate Cancer As of 2005, recurrent translocations were only associated with sporadic solid tumors in sarcoma, some thyroid cancers, and pediatric malignancies. Using gene expression arrays and a bioinformatics filtering algorithm called cancer outlier profile analysis (COPA), Chinnaiyan and coworkers first identified recurrent translocations occurring in prostate cancer, finding juxtaposition of the 5′ untranslated region of…

Androgen Receptor

Introduction The androgen receptor (AR) is part of the steroid hormone receptor family of molecules, which also includes the progesterone, estrogen, mineralocorticoid, retinoic acid, thyroid, and vitamin D receptors. The AR is a transcription factor, primarily responsible for mediating the physiologic effects of androgens through binding of the androgen–AR complex to specific DNA target sequences and inducing or suppressing the transcription of target genes. Androgen receptor…

Inflammation and Infection in the Etiology of Prostate Cancer

Introduction The idea of a link between inflammation and cancer is not unique to prostate cancer (PCa). The idea of an association between inflammation and cancer dates back at least 150 years. In 1863, Virchow proposed that cancer originates at sites of chronic inflammation. Chronic inflammation has been estimated to contribute to 15–20% of cancers and has been linked specifically to stomach cancer from Helicobacter pylori…

Population Screening for Prostate Cancer and Early Detection

Introduction Prostate cancer (PCa) is the most commonly diagnosed new solid cancer and the second most common cause of cancer-related deaths in men in the United States. The American Cancer Society (ACS) estimated that approximately 241,740 new cases and 28,170 PCa-related deaths would occur in the United States in 2014. PCa is now the second-leading cause of cancer death in men, exceeded only by lung cancer.…

Complications associated with allogeneic hematopoietic cell transplantation in children

1 Why is it important to understand complications after allogeneic hematopoietic cell transplantation? Allogeneic hematopoietic cell transplantation (AlloHCT) is a lengthy and complex process. The majority of the patients sustain complications after AlloHCT. These complications can have a significant impact on survival, quality of life, cost, and healthcare utilization. Hence, it is crucial to understand the landscape of complications after alloHCT. 2 How do we classify…

Stem cell transplantation for children with nonmalignant disorders

The concept of stem cell transplant was first performed in 1956 in a patient with leukemia; however, this was quickly applied to nonmalignant disorders only a decade later in a patient with severe combined immunodeficiency. In patients with nonmalignant conditions, the goal is to replace a missing gene or enzyme in the hematopoietic/immune systems or to replete a bone marrow that is not functioning. Historically, conditioning…

Hematopoietic cell transplantation for malignant disorders

1 How do the goals of autologous transplantation and allogeneic transplantation differ? Hematopoietic cell transplantation (HCT) is the act of restoring hematopoiesis by infusing hematopoietic stem cells. The cells that are infused can be from another person (allogeneic) or previously collected cells from the recipient (autologous). The goals and expectations between allogeneic and autologous transplantation differ. Autologous transplantation is most used for children with chemotherapy-sensitive malignancies,…

Gene therapy for hemoglobinopathies and other diseases

Hemoglobinopathies are genetically inherited conditions that originate from the lack or malfunction of components that comprise the hemoglobin (Hb) protein. Sickle cell disease (SCD) and thalassemia are the most common forms of these conditions. SCD is caused by a well-defined point mutation in the β-globin gene and therefore is an optimal target for hematopoietic stem cell (HSC) gene-addition/editing therapy. Similarly, β-thalassemias are caused by point mutations…

Car-T cells: expanding the universe of immunotherapy in children with malignant diseases

1 What are chimeric antigen receptor–T cells? Chimeric antigen receptor (CAR)-T cells are a powerful form of adoptive cell therapy. In their native state, T cells do not express antigens targeted to bind to malignant cells. In CAR-T therapy, T cells are harvested from a patient and then genetically engineered using a viral vector (most commonly a lentiviral or retroviral vector) to produce proteins on their…

Autologous hematopoietic stem cell transplantation for children and young adults

Autologous hematopoietic stem cell transplant (auto HSCT) uses patient-derived stem cells to facilitate recovery from myeloablative high-dose chemotherapy for cancer. The concept is that higher doses of certain agents, particularly alkylators, will be 3 to 15 times more potent than conventional doses and will be useful as consolidation therapy after initial cytoreduction, provided nonhematologic toxicity remains acceptable. Use of intensive chemotherapy may also permit deferral or…

Principles and practice of pediatric hematopoietic cell transplantation

1 Describe the types of transplant and their indications. Type of Transplant Details of Transplant Indications Disadvantages Autologous hematopoietic stem cell transplantation (autoHCT) Use patient’s own hematopoietic cells. Give granulocyte colony-stimulating factor (G-CSF) and/or Plerixafor to mobilize cells to collect. Collect after initial cycle(s) of chemotherapy. Goal collection: 5 million/kg of CD34 + cells (higher if multiple transplants planned) Goal: High doses of chemotherapy will eliminate…

Hemophagocytic lymphohistiocytosis

1 What is the definition of hemophagocytic lymphohistiocytosis? Hemophagocytic lymphohistiocytosis (HLH) is a rare but potentially fatal clinical syndrome of severe pathologic immune activation, characterized by signs and symptoms of excessive inflammation. It commonly appears in infancy but can be found in any age group. There are both genetic (primary) and acquired (secondary) forms. Immunologic basis for HLH is presumed because of its inflammatory nature and…