Epidemiology of non-alcoholic fatty liver disease and risk of hepatocellular carcinoma progression

Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide. Its incidence has grown alongside the increasing global prevalence of type 2 diabetes, obesity, and metabolic syndrome. The risk of progression to hepatocellular carcinoma for nonalcoholic steatohepatitis patients over 5 years is 8%, and despite targeted and immunotherapy treatment advances, HCC maintains a bleak 5-year survival of 19%. NAFLD’s primary risk factors are components of metabolic syndrome as well as possible sleep disturbances. NAFLD is most common among men 50-60 years of age, though incidence in women catches up after menopause. In the US, Hispanics are most likely to develop NAFLD and African Americans least likely, in part due to the prevalence of the PNPLA3 gene variant. With NAFLD risk factors especially prevalent in underserved populations and developing nations, public health interventions, earlier diagnosis, and novel treatments could curb the growing disease burden

Immunotherapies and Targeted Therapies in the Treatment of Metastatic Colorectal Cancer

Colorectal cancer (CRC) is the third leading cause of cancer deaths, and while mortality has largely improved in the developed world, five-year survival for metastatic disease remains dismally low at only 15%. Fortunately, nearly a dozen targeted therapies and immunotherapies have been FDA approved in the past decade for certain patient profiles with metastatic CRC (mCRC), and many others are under development. Checkpoint inhibitors such as pembrolizumab have proven effective at extending survival for mismatch repair (MMR)-deficient and high microsatellite instability (MSI) mCRC patients. In combination with chemotherapy in first- and second-line treatment, antiangiogenic (anti-vascular endothelial growth factor (anti-VGEF)) agent bevacizumab has been shown to increase mCRC survival. Anti-epidermal growth factor receptor (anti-EGFR) agents panitumumab and cetuximab, in combination with chemotherapy, have also prolonged survival among KRAS and all RAS wild-type mCRC patients. Among these patients, anti-EGFR therapy has been found to be more efficacious than bevacizumab. Improved selectivity has allowed small-molecule receptor tyrosine kinase (RTK) inhibitors to target VEGF and EGFR with greater efficacy and tolerability. Combinations of immunotherapies, RTKs, monoclonal antibodies, and cytotoxic drugs are being investigated to provide broad-spectrum protection against relapse by simultaneously targeting many cancer hallmarks. Lastly, human epidermal growth factor receptor 2 (HER2) therapy has shown promise for HER2-positive mCRC patients, though larger clinical trials are required to secure FDA approval

Epidemiology of Cancers of the Small Intestine: Trends, Risk Factors, and Prevention

The latest data from the United States and Europe reveal that rare small intestine cancer is on the rise, with the number of cases having more than doubled over the past 40 years in the developed world. Mortality has grown at a slower pace, thanks to improvements in early diagnosis and treatment, as well as a shift in the etiology of neoplasms affecting the small intestine. Nevertheless, 5-year survival for small intestine adenocarcinomas has lingered at only 35%. Lifestyle in developed nations, including the rise in obesity and physical inactivity, consumption of alcohol, tobacco, and red and processed meats, and occupational exposures may be to blame for the proliferation of this rare cancer. Identification of hereditary and predisposing conditions, likely to blame for some 20% of cases, may help prevent and treat cancers of the small intestine. Studies of the neoplasm have been limited by small sample sizes due to the rarity of the disease, leaving many questions about prevention and treatment yet to be answered

Epidemiology of Melanoma

Melanoma accounts for 1.7% of global cancer diagnoses and is the fifth most common cancer in the US. Melanoma incidence is rising in developed, predominantly fair-skinned countries, growing over 320% in the US since 1975. However, US mortality has fallen almost 30% over the past decade with the approval of 10 new targeted or immunotherapy agents since 2011. Mutations in the signaling-protein BRAF, present in half of cases, are targeted with oral BRAF/MEK inhibitor combinations, while checkpoint inhibitors are used to restore immunosurveillance likely inactivated by UV radiation. Although the overall 5-year survival has risen to 93.3% in the US, survival for stage IV disease remains only 29.8%. Melanoma is most common in white, older men, with an average age of diagnosis of 65. Outdoor UV exposure without protection is the main risk factor, although indoor tanning beds, immunosuppression, family history and rare congenital diseases, moles, and obesity contribute to the disease. Primary prevention initiatives in Australia implemented since 1988, such as education on sun-protection, have increased sun-screen usage and curbed melanoma incidence, which peaked in Australia in 2005. In the US, melanoma incidence is not projected to peak until 2022–2026. Fewer than 40% of Americans report practicing adequate protection (sun avoidance from 10 a.m.–4 p.m. and regular application of broad-spectrum sunscreen with an SPF > 30). A 2-4-fold return on investment is predicted for a US sun-protection education initiative. Lesion-directed skin screening programs, especially for those at risk, have also cost-efficiently reduced melanoma mortality

Targeted Therapies and Immunotherapies in the Treatment of Esophageal Cancers

Esophageal cancer (EC) is among the most frequent and deadly cancers around the world. While esophageal adenocarcinoma (EAC) has one of the fastest-growing incidences amongst cancers in the US, it also has one of the lowest survival rates due to the limited effective treatment options. Fortunately, in the past decade, two targeted therapies and an immunotherapy agent have been approved by the FDA for metastatic EAC and esophageal squamous cell carcinoma (ESCC), with several more currently being considered for approval. In terms of immunotherapies, in July 2019, the FDA approved the PD1 inhibitor pembrolizumab for second-line treatment of PDL1-positive, advanced or metastatic ESCC. Two years before, pembrolizumab had been approved for the third-line treatment of PDL1-positive EAC. The PD1 inhibitor nivolumab, which was found in one study to outperform chemotherapy irrespective of PDL1 status, has yet to secure FDA approval. In terms of targeted therapies, although as many as 90% of EC cases show upregulated EGFR, anti-EGFR therapy has not been shown to improve survival. Ramucirumab, an antibody targeting both VEGF and HER2/neu receptors, has been approved for the treatment of refractory EAC, while the anti-HER2 monoclonal antibody (mAb) trastuzumab has been approved as front-line treatment for HER2-positive cases which account for approximately 20% of ECs. Although these targeted therapies and immunotherapies have resulted in significant improvements in survival for specific patient populations that are positive for certain biomarkers, such as PDL1 and HER2/neu, the survival rates remain low for a large proportion of the metastatic EC patient population, necessitating the development of further targeted treatment options

Epidemiology of Melanoma

Melanoma accounts for 1.7% of global cancer diagnoses and is the fifth most common cancer in the US. Melanoma incidence is rising in developed, predominantly fair-skinned countries, growing over 320% in the US since 1975. However, US mortality has fallen almost 30% over the past decade with the approval of 10 new targeted or immunotherapy agents since 2011. Mutations in the signaling-protein BRAF, present in half of cases, are targeted with oral BRAF/MEK inhibitor combinations, while checkpoint inhibitors are used to restore immunosurveillance likely inactivated by UV radiation. Although the overall 5-year survival has risen to 93.3% in the US, survival for stage IV disease remains only 29.8%. Melanoma is most common in white, older men, with an average age of diagnosis of 65. Outdoor UV exposure without protection is the main risk factor, although indoor tanning beds, immunosuppression, family history and rare congenital diseases, moles, and obesity contribute to the disease. Primary prevention initiatives in Australia implemented since 1988, such as education on sun-protection, have increased sun-screen usage and curbed melanoma incidence, which peaked in Australia in 2005. In the US, melanoma incidence is not projected to peak until 2022–2026. Fewer than 40% of Americans report practicing adequate protection (sun avoidance from 10 a.m.–4 p.m. and regular application of broad-spectrum sunscreen with an SPF > 30). A 2-4-fold return on investment is predicted for a US sun-protection education initiative. Lesion-directed skin screening programs, especially for those at risk, have also cost-efficiently reduced melanoma mortality

Valvular Heart Disease Epidemiology

Valvular heart disease is a rapidly growing cause of global cardiovascular morbidity and mortality with diverse and evolving geographic distribution. The prevalence of rheumatic heart disease, the most common valvular heart disease (affecting approximately 41 million people), has been rising in developing nations, likely due to the expansion of the young adult population and the decrease in premature mortality that has resulted from improved access to antibiotics, microbiological testing, and echocardiography. Rheumatic heart disease has also been rising among the impoverished and, often, indigenous populations of developed nations, spurring public health initiatives that are aimed at alleviating healthcare disparities. Aortic valve stenotic disease is the most commonly occurring valvular pathology in developed nations (afflicting 9 million people worldwide) and its prevalence has been increasing with population aging and the increased prevalence of atherosclerosis. Aortic regurgitation is associated with diastolic, but not systolic, hypertension and it has likewise seen a rise in the developed world. Mitral regurgitation affects 24 million people worldwide, with great variability between and among nations. Primary mitral regurgitation arises as a consequence of myxomatous degeneration and mitral valve prolapse, which is largely due to genetic predispositions, while secondary mitral regurgitation accounts for 65% of cases and arises secondary to dilation and heart failure. Tricuspid regurgitation has become more prevalent in developed nations due to the increased usage of intracardiac pacemakers. Infective endocarditis prevalence has also grown in developed nations, likely due to population aging and the increased utilization of transcatheter valve replacement and prosthetic valves as interventions against the previously discussed valvular pathologies

Epidemiology of Non-Hodgkin’s Lymphoma

Non-Hodgins’s lymphoma (NHL) is the most common hematological malignancy worldwide, accounting for nearly 3% of cancer diagnoses and deaths. NHL is the seventh most prevalent cancer and has the sixth highest mortality among cancers in the US. NHL accounts for 4% of US cancer diagnoses, and incidence has increased 168% since 1975 (while survival has improved 158%). NHL is more common among men, those >65 years old, and those with autoimmune disease or a family history of hematological malignancies. NHL is a heterogenous disease, with each subtype associated with different risk factors. Marginal zone lymphoma (MZL) is strongly associated with Sjogren’s syndrome (SS) and Hashimoto’s thyroiditis, while peripheral T-cell lymphoma (PTCL) is most associated with celiac disease. Occupational exposures among farm workers or painters increases the risk of most of the common subtypes. Prior radiation treatment, obesity, and smoking are most highly associated with diffuse large B-cell lymphoma (DLBCL), while breast implants have been rarely associated with anaplastic large cell lymphoma (ALCL). Infection with Epstein–Barr Virus (EBV) is strongly associated with endemic Burkitts lymphoma. HIV and human herpes virus 8 (HHV-8), is predisposed to several subtypes of DLBCL, and human T-cell lymphoma virus (HTLV-1) is a causative agent of T-cell lymphomas. Obesity and vitamin D deficiency worsen NHL survival. Atopic diseases and alcohol consumption seem to be protective against NHL

Epidemiology, Staging and Management of Prostate Cancer

Prostate cancer is the second most common and fifth most aggressive neoplasm among men worldwide. It is particularly incident in high human development index (HDI) nations, with an estimated one in seven men in the US receiving a prostate cancer diagnosis in their lifetime. A rapid rise and then fall in prostate cancer incidence in the US and Europe corresponded to the implementation of widespread prostate specific antigen (PSA) testing in 1986 and then subsequent fall from favor due to high rates of false positives, overdiagnosis, and overtreatment (as many as 20–50% of men diagnosed could have remained asymptomatic in their lifetimes). Though few risk factors have been characterized, the best known include race (men of African descent are at higher risk), genetics (e.g., BRCA1/2 mutations), and obesity. The Gleason scoring system is used for histopathological staging and is combined with clinical staging for prognosis and treatment. National guidelines have grown more conservative over the past decades in management, recommending watchful waiting and observation in older men with low to intermediate risk disease. Among higher risk patients, prostatectomy (robotic is preferred) and/or external beam radiotherapy is the most common interventions, followed by ADT maintenance. Following progression on androgen deprivation therapy (ADT) (known as castration-resistance), next generation endocrine therapies like enzalutamide, often in combination with cytotoxic agent docetaxel, are standard of care. Other promising treatments include Radium-223 for bone metastases, pembrolizumab for programmed death ligand-1 (PDL1) and microsatellite instability (MSI) high disease, and poly ADP ribose polymerase (PARP) inhibitors for those with mutations in homologous recombination (most commonly BRCA2)