Serotonin Pathway in Cancer.

Serotonin (5-hydroxytryptamine, 5-HT) is a biogenic monoamine produced from the essential amino acid tryptophan. Serotonin's role as a neurotransmitter in the central nervous system and a motility mediator in the gastrointestinal tract has been well defined, and its function in tumorigenesis in various cancers (gliomas, carcinoids, and carcinomas) is being studied. Many studies have shown a potential stimulatory effect of serotonin on cancer cell proliferation, invasion, dissemination, and tumor angiogenesis. Although the underlying mechanism is complex, it is proposed that serotonin levels in the tumor and its interaction with specific receptor subtypes are associated with disease progression. This review article describes serotonin's role in cancer pathogenesis and the utility of the serotonin pathway as a potential therapeutic target in cancer treatment. Octreotide, an inhibitor of serotonin release, is used in well-differentiated neuroendocrine cancers, and the tryptophan hydroxylase (TPH) inhibitor, telotristat, is currently being investigated in clinical trials to treat patients with metastatic neuroendocrine tumors and advanced cholangiocarcinoma. Several in vitro studies have shown the anticancer effect of 5-HT receptor antagonists in various cancers such as prostate cancer, breast cancer, urinary bladder, colorectal cancer, carcinoid, and small-cell lung cancer. More in vivo studies are needed to assess serotonin's role in cancer and its potential use as an anticancer therapeutic target. Serotonin is also being evaluated for its immunoregulatory properties, and studies have shown its potential anti-inflammatory effect. Therefore, it would be of interest to explore the combination of serotonin antagonists with immunotherapy in the future.

PARP inhibitors in castration-resistant prostate cancer.

Somatic or germline mutations in genes regulating DNA damage repair have been noted in around 20% of patients with advanced prostate cancer. Poly-ADP-ribose polymerase (PARP) inhibitors have shown encouraging efficacy in prostate cancer patients with DNA repair mutations. Two PARP inhibitors, olaparib, and rucaparib have recently received FDA approval for treatment of patients with advanced castration-resistant prostate cancer (CRPC), while several trials with other PARP inhibitors are ongoing. Here, we briefly summarize the current data supporting the efficacy of PARP inhibitors in advanced CRPC.

Hypokalemic Paralysis Secondary to Immune Checkpoint Inhibitor Therapy.

Introduction of immune checkpoint inhibitors (ICIs) has led to significant improvements in the treatment of multiple malignancies. Anti-programmed cell death protein 1 (PD-1) and anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) are two essential ICIs that have been FDA approved since 2011. As the use of immunotherapy in melanoma and other malignancies increases, the potential of adverse events also increases. Overall, anti-PD-1 agents are well tolerated. In rare instances, colitis, endocrinopathies, skin, and renal toxicities have been observed. A 58-year-old male with a history of stage 4 cutaneous melanoma presented with quadriplegia while on nivolumab. Routine blood test revealed low potassium, low bicarbonate, and high serum creatinine. Admission diagnosis included hypokalemia, acute kidney injury, and renal tubal acidosis. The offending drug was discontinued, and the patient was started on high-dose corticosteroids. On discharge, paralysis was resolved. Renal function and potassium were normalized. Nivolumab was discontinued, and he was started on pembrolizumab. Literature suggests that, although rare, patients receiving ICE may develop immune-mediated nephritis and renal dysfunction. The mainstay of immune-related adverse event (irAE) management is immune suppression. Hence, given the increasing frequency of immunotherapy use, awareness should be raised in regard to irAEs and their appropriate management.

Anomalous Origin of Right Coronary Artery Originating from the Pulmonary Trunk (ARCAPA): an Incidental Finding in a Patient Presenting with Chest Pain.

Anomalous origin of the right coronary artery originating from the pulmonary trunk (ARCAPA) is a rare congenital coronary anomaly with an estimated prevalence of 0.002%. Most patients are asymptomatic and the anomaly is detected incidentally during evaluation for other problems. Occasionally, ARCAPA may lead to myocardial ischemia and/or sudden cardiac arrest. We present a case of a 55-year-old female with a history of hypertension who presented to the emergency department with intermittent chest discomfort for three days. Laboratory results showed an elevated troponin of 0.18 ng/ml and subsequently increased to 0.39 ng/ml. The initial electrocardiogram study demonstrated sinus tachycardia with no acute changes. The patient was diagnosed with non-ST-segment elevation myocardial infarction. She underwent cardiac catheterization that showed 90% stenosis of the left main/left anterior descending artery. Reflux of contrast from the right coronary artery (RCA) ostium to the pulmonary artery was seen along with left to right collaterals with retrograde filling of the RCA. There was no significant obstruction of the RCA when viewed via left to right collaterals. Right heart catheterization and pulmonary angiography were performed which confirmed the origin of the RCA from the pulmonary trunk. The patient was referred for surgery and ligation of the aberrant RCA originating from the pulmonary artery was performed along with coronary artery bypass grafting x 2, left internal mammary artery to left anterior descending artery (LAD) and saphenous vein graft to the proximal posterior descending artery. The patient was discharged home with marked improvement of her symptoms. Origin of the RCA from the pulmonary artery (ARCAPA) is a rare congenital malformation with a potentially malignant outcome for the patient. The majority of patients with ARCAPA remain asymptomatic. In this case report, the chest discomfort was due to occlusion of the LAD and was probably unrelated to the coronary malformation. However, sudden cardiac death has been linked to ARCAPA and therefore a corrective operation is recommended even for asymptomatic patients. Of the surgical techniques available, which include: simple ligation of the RCA, ligation of the RCA with saphenous vein bypass grafting and re-implantation of the RCA into the aorta, the last method is believed to be superior for the restoration of myocardial blood supply. However, its long-term benefits have not been conclusively demonstrated. Therefore, in our patient, ligation of RCA with saphenous vein bypass grafting was done as it is recognized as a less traumatic surgical alternative to RCA implantation into the aorta.