Reintroduction of 5-Fluorouracil Post-cardiac Arrest Secondary to Chemotherapy-Induced Cardiotoxicity.

5-fluorouracil (5-FU) has been known to have cardiotoxic side effects, including coronary vasospasm, myocardial infarctions, heart failure, arrhythmias, and cardiac arrest. These cases have been reported in patients with either known coronary disease or known risk factors. In cases of acute cardiotoxicity, cessation of fluoropyrimidines is recommended, and reintroduction of the medication is generally avoided. We present a case of a young patient with no known risk factors for coronary disease, who presented with an acute cardiac arrest suspected secondary to vasospasm from the administration of 5-FU for the treatment of rectal cancer and was successfully maintained on treatment with 5-FU post-arrest after transitioning from an infusion to bolus administration.

Feasibility of blood testing combined with PET-CT to screen for cancer and guide intervention.

Cancer treatments are often more successful when the disease is detected early. We evaluated the feasibility and safety of multicancer blood testing coupled with positron emission tomography-computed tomography (PET-CT) imaging to detect cancer in a prospective, interventional study of 10,006 women not previously known to have cancer. Positive blood tests were independently confirmed by a diagnostic PET-CT, which also localized the cancer. Twenty-six cancers were detected by blood testing. Of these, 15 underwent PET-CT imaging and nine (60%) were surgically excised. Twenty-four additional cancers were detected by standard-of-care screening and 46 by neither approach. One percent of participants underwent PET-CT imaging based on false-positive blood tests, and 0.22% underwent a futile invasive diagnostic procedure. These data demonstrate that multicancer blood testing combined with PET-CT can be safely incorporated into routine clinical care, in some cases leading to surgery with intent to cure.

Perioperative management of cold agglutinin autoimmune hemolytic anemia in an older adult undergoing radical cystectomy for bladder cancer.

Patients diagnosed with bladder cancer are most frequently older adults who have multiple chronic conditions. Frequently, new conditions are unmasked during preoperative evaluation for surgery such as radical cystectomy. We report the case of an 85 year old male with muscle invasive bladder cancer who was concurrently diagnosed with cold agglutinin hemolytic anemia. This case demonstrates the importance of close attention to underlying chronic conditions in older adults considering major cancer surgery and the need for multidisciplinary management in medically complex cases.

Palliative Care in Lung Cancer: When to Start.

PURPOSE OF REVIEW: Despite recent advances in the care of patients with advanced non-small cell lung cancer (NSCLC), significant morbidity and mortality remains. Symptoms caused by the cancer and its treatments can be profoundly debilitating. Palliative care aims to reduce this burden. In this review, we discuss the definition, purpose, benefits, and optimal timing of palliative care in advanced NSCLC. RECENT FINDINGS: Several studies evaluating the value of early palliative care for patients with advanced NSCLC and other advanced malignancies have identified benefits for patients, caregivers, and health systems. For patients with advanced NSCLC, introduction of palliative care early in the disease course improves quality of life and even overall survival. Early institution of palliative care should become standard of care for patients with advanced NSCLC.

Cancer Clonal Theory, Immune Escape, and Their Evolving Roles in Cancer Multi-Agent Therapeutics.

PURPOSE OF REVIEW: The knowledge base of malignant cell growth and resulting targets is rapidly increasing every day. Clonal theory is essential to understand the changes required for a cell to become malignant. These changes are then clues to therapeutic intervention strategies. Immune system optimization is a critical piece to find, recognize, and eliminate all cancer cells from the host. Only by administering (1) multiple therapies that counteract the cancer cell's mutational and externally induced survival traits and (2) by augmenting the immune system to combat immune suppression processes and by enhancing specific tumor trait recognition can cancer begin to be treated with a truly targeted focus. RECENT FINDINGS: Since the sequencing of the human genome during the 1990s, steady progress in understanding genetic alterations and gene product functions are being unraveled. In cancer, this is proceeding very fast and demonstrates that genetic mutations occur very rapidly to allow for selection of survival traits within various cancer clones. Hundreds of mutations have been identified in single individual cancers, but spread across many clones in the patient's body. Precision oncology will require accurate measurement of these cancer survival-benefiting mutations to develop strategies for effective therapy. Inhibiting these cellular mechanisms is a first step, but these malignant cells need to be eliminated by the host's mechanisms, which we are learning to direct more specifically. Cancer is one of the most complicated cellular aberrations humans have encountered. Rapidly developing significant survival traits require prompt, repeated, and total body measurements of these attributes to effectively develop multi-agent treatment of the individual's malignancy. Focused drug development to inhibit these beneficial mutations is critical to slowing cancer cell growth and, perhaps, triggering apoptosis. In many cases, activation and targeting of the immune system to kill the remaining malignant cells is essential to a cure.

Differential development of central dopaminergic and serotonergic systems in BALB/c and C57BL/6J mice.

Although the etiology of autism is unclear, disruptions of the dopaminergic and serotonergic systems have been associated with the disorder. Based on behavioral differences observed in the BALB/c strain of mice in comparison to other strains, notably, C57BL/6J mice, it has been suggested that the BALB/c strain may serve as an animal model of autism. However, to date, most work investigating neural and behavioral abnormalities in this strain has been performed in adult animals. Therefore, the present study was conducted to examine the development of the central dopaminergic and serotonergic systems of BALB/c mice as compared to C57BL/6J mice. Levels of dopamine, serotonin, and their metabolites in several different brain regions and at three ages during development were measured. Alterations in both monoaminergic systems associated with age and strain were detected across brain regions indicating that there are neurochemical differences between these strains early in life. However, despite these differences in the development of brain monoaminergic systems, it remains difficult to declare this strain as a valid model of autism.

Animal model of autism using GSTM1 knockout mice and early post-natal sodium valproate treatment.

Autism is a heterogeneous, behaviorally defined developmental disorder with unknown etiology but thought to be the result of environmental insult acting upon the developing brain of a genetically susceptible individual. Approximately 30% of individuals with autism have normal development up to the age of about 30 months after which they experience behavioral regression and lose previously acquired motor, cognitive and social skills. Early post-natal toxicant administration to mice has been used to model autistic regression. To test the hypothesis that genetically altered mice might be more sensitive to toxicant exposure early in life, mice with a deletion of glutathione-S-transferaseM1 (GSTM1; a gene associated with increased risk of autism that codes for an enzyme involved in the management of toxicant-induced oxidative stress) and wild-type controls were exposed to valproic acid (VPA; a toxicant known to cause autism-like behavioral deficits that, in part, are mediated through oxidative stress) on post-natal day 14. VPA treatment caused significant increases in apoptosis in granule cells of the hippocampus and cerebellum. There was a genotype by treatment by sex interaction with wild-type females exhibiting significantly fewer apoptotic cells in these regions compared to all other groups. VPA treatment also resulted in long-lasting deficits in social behaviors and significant alterations in brain chemistry. VPA-treated GSTM1 knockout animals performed significantly fewer crawl-under behaviors compared to saline-treated knockout animals as well as wild-type controls receiving either treatment. Collectively, these studies indicate that VPA-treatment causes cerebellar and hippocampal apoptosis and that having the wild-type GSTM1 genotype may confer protection against VPA-induced neuronal death in female mice.