Abnormal Dihydropyrimidine Dehydrogenase Activity as an Indicator of Potential 5-Fluorouracil Linked Cardiotoxicity in Colorectal Cancer Patients: Are Toxic Events Inevitable?

Colorectal cancer (CRC) treatment can be limited to surgical resection for low stages of the disease while subsequent chemotherapy is the preferred treatment for the higher-stage disease. This chemotherapy relies heavily on fluoropyrimidine: 5-fluorouracil (5-FU) and capecitabine, a role played for decades. Fluoropyrimidine-linked treatment can present important and even lethal toxic events at the cardiac level like acute coronary syndrome, arrhythmias, and death. The production of these toxic events depends on the capacity of a subject to metabolize the fluoropyrimidines adequately, and this depends on the activity of the enzyme dihydropyrimidine dehydrogenase (DPD). Any change that affects the quantity or quality of this enzyme will compromise its capacity to metabolize the fluoropyrimidines. The resultant abnormal enzyme activity exposes the patient to continuously high levels of the chemotherapeutic agent or its catabolites. Consequently, the patient becomes more susceptible to pyrimidine-linked toxic adverse events. Genetic testing of patients for potential decreased DPD activity before subjecting them to fluoropyrimidine-based chemotherapy will help identify subjects at greater risk of increased cardiotoxicities, the possibility of prompt intervention, should these appear, and a multidisciplinary strategy aimed at managing these cases. Potential cases of cardiotoxicity in CRC patients, candidates to fluoropyrimidine toxicities, can be anticipated by pretreatment screening of DPD activity. Pretreatment screening will reduce many hospitalizations with a consequent decrease in costs both to the patients and the healthcare system. This review article will examine the 5-FU linked cardiotoxicity, known correlated risk factors, clinical manifestations, management strategy, and the role of genetic testing in identifying high-risk patients.

Hypothyroidism-Related Cardiac Tamponade.

Thyroid dysfunction is a common incidental finding among healthy individuals. It can affect various organs of the body, including the heart. Among many other heart complications, it can lead to pericardial effusion by causing increased permeability of albumin across the pericardial membrane that leads to exudative pericardial effusion. In hypothyroidism, the fluid collection process occurs over a period of months, giving enough time for the pericardial membrane to stretch and accommodate the fluid within itself without causing any symptoms. Eventually, the pericardial membrane stretches to its maximum capacity and has no room to accommodate any more fluid, resulting in cardiac tamponade in the patients. Patients with hypothyroidism-related cardiac tamponade usually remain asymptomatic or present with atypical symptoms such as bradycardia and a normal heart rate or high blood pressure, and the diagnosis comes into light only when patients present to the hospital with hemodynamic instability. In these cases, echocardiography successfully detects large pericardial effusion with collapsed cardiac chambers. To treat hypothyroidism-related cardiac tamponade, treating the underlying condition has been very successful in the majority of the asymptomatic patients, but pericardiocentesis is required in emergencies to relieve symptoms of patients presenting with hemodynamic instability. We believe hypothyroidism-related cardiac tamponade is a preventable condition if detected and treated in outpatient settings by family physicians. This will prevent occurrence of various complications arising from hypothyroidism, including pericardial effusion. This will lead to a better quality of life among patients with the added benefit of reduced health care burden due to reduced frequency of hospital admissions of acutely ill patients.

Chronic Neutrophilic Leukemia: A Literature Review of the Rare Myeloproliferative Pathology.

Hematological malignancies often develop due to a vast spectrum of environmental and genetic etiologies. Chronic neutrophilic leukemia (CNL) can be described as a BCR-ABL1 (Philadelphia chromosome)-negative myeloproliferative neoplastic disease with various genetic mutations that may directly or indirectly play a role in its pathogenesis. A well-established mutation in CNL is the CSF3R (a cytokine receptor) which has been incorporated into the diagnostic criteria for the disease. However, evidence of other mutations such as SETBP1, ASXL1, and TET2 has also shed more light on the pathogenesis of this condition. Due to the unknown incidence and heterogeneous presentation of the disease, the diagnosis and management are often difficult and lack satisfactory data. The purpose of this review is to yield further insight into a disease that lacks awareness in the medical community. Using PubMed as a database, relevant studies and case reports were reviewed. The data compiled were used to acknowledge the disease in terms of etiology, clinical manifestation, molecular pathogenesis, and available treatment modalities. Though existing treatment modalities have been shown to induce clinical improvement, the outcomes are not reliable, and further research is required to reach a comprehensive "standard of care" for the disease.

The Significance of the Mediterranean Diet in the Management of Non-Alcoholic Fatty Liver Disease: A Systematic Review.

Non-alcoholic fatty liver disease (NAFLD) is the accumulation of intrahepatic fat occurring in the absence of alcohol abuse. The fatty changes in the liver are often the beginning of sequelae of complications, potentially causing steatohepatitis, liver cirrhosis, and hepatocellular carcinoma. The Mediterranean diet is not only a way of eating but is considered a lifestyle and primarily consists of a plant-based diet, with olive oil as the primary lipid. In this study, we reviewed the effectiveness of the Mediterranean diet on NAFLD and its efficacy in disease management. This systematic review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol (PRISMA-P) 2009 guidelines. The PubMed database was used to gather articles, using the following terms individually and in combination, "Mediterranean diet," "non-alcoholic fatty liver disease," "insulin resistance," "metabolic syndrome," "omega-3-fatty acids." A quality appraisal was completed to include 14 articles in this systematic review. The studies discuss the correlation between the Mediterranean diet and its role in preventing and treating NAFLD. Olive oil is the major monounsaturated fatty acid, whereas nuts, seeds, and fish consist largely of polyunsaturated fatty acids, both of which are essential components of the Mediterranean diet. The plant-based diet, having sufficient amounts of vegetables, legumes, and fruits, provides its anti-oxidant and anti-inflammatory effects, playing a fundamental role in preventing oxidative stress damage. Olive oil polyphenols increase apoptosis and cell cycle arrest. They also decrease proliferation and angiogenesis, all of which prevent neoplasia. Adapting the Mediterranean lifestyle has shown promising effects in NAFLD, reducing overall mortality and morbidity.

The Importance of Measuring Troponin in Chronic Obstructive Pulmonary Disease Exacerbations: A Systematic Review.

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide. Many patients with acute exacerbations need intensive care. There are many cardiovascular risk factors and comorbid conditions linked with COPD. Troponin elevation is used for the diagnosis of myocardial infarction. However, it is commonly elevated in patients with COPD. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed and Scopus were searched for relevant articles. A total of 383 papers were identified. Out of the 383 papers, only 30 papers remained for final synthesis after removing duplicates, screening for relevant articles, and assessing eligibility criteria. After the quality appraisal, 11 papers were chosen for inclusion in this study. COPD is characterized by obstruction and inflammation of the airways. It is caused mainly by smoking, by causing harmful changes in the structure of the airways. It usually presents with dyspnea, cough, and/or production of sputum. Troponins are regulatory proteins found in the myocardium and skeletal muscles. The cause of its elevation in COPD and acute exacerbated chronic obstructive pulmonary disease (AECOPD) remains unclear. However, several reasons and factors have been suggested. The most intriguing fact is that high troponin in COPD, especially in exacerbations, has been linked in many articles to a higher risk of death. Furthermore, it could serve as a tool for better assessment and management of COPD patients. We found that troponin predicts death and poor outcomes in COPD and AECOPD. The exact mechanism of its elevations is not clear. We believe it can be a valuable tool for clinicians in better managing COPD and assessing the severity of the exacerbations.

Emergency surgery for complicated colorectal cancer. A two-decade trend analysis.

BACKGROUND/AIMS: Emergency procedures for colorectal cancer have worse outcomes than elective resections. Temporal trends in emergency surgery are analyzed by comparing two decade-related series of colorectal cancer patients. METHODS: The clinical data of 985 patients undergoing colorectal cancer surgery were collected during two decades (1975-1984 and 1995-2004). Rates of emergency surgery, operative mortality, 5-year cancer-related and overall survival were compared retrospectively. RESULTS: The rate of emergency surgery decreased from 81 out of 513 cases (16%) during 1975-1984 to 41 out of 471 cases (9%) during 1995-2004 (p = 0.005). Over the same time, the rate of curative resections in emergency increased from 46% (37/81 cases) to 76% (31/41 cases) (p < 0.001), while patient and tumor characteristics remained similar. Operative mortality after emergency procedures decreased from 14% (11 deaths) to 5% (2 deaths) and cancer-related survival increased from 21 to 42% (p = 0.03). However, when excluding palliative procedures, survival after emergency surgery increased from 52 to 58%, while after elective treatment it increased from 56 to 78% (p < 0.001). CONCLUSIONS: Frequency and operative mortality of emergency colorectal cancer surgery decreased substantially from 1975-1984 to 1995-2004. No significant improvement in long-term survival was observed when curative emergency resections only were considered. Further efforts are needed to reverse the diverging trend of long-term outcomes between emergency and elective curative procedures.