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

Time to initiation of antiresorptive agents in multiple myeloma to reduce skeletal related events

PurposeCurrent treatment guidelines strongly support the use of antiresorptive therapy in patients with newly diagnosed multiple myeloma (NDMM) with the goal of preventing skeletal related events (SRE). Despite these concrete, data-driven recommendations, the impact of delays in antiresorptive initiation in NDMM patients is understudied. Through a multicenter retrospective study, we examined the impact of delays in antiresorptive initiation on the rates of SREs. We furthered our exploration of this topic in a separate retrospective analysis with a focus on reasons for delays in antiresorptive therapy initiation.MethodsElectronic health records from two large academic institutions were used to identify patients with NDMM between July 1, 2016, and June 30, 2019. Exclusion criteria included patients with previous antiresorptive use and patients never prescribed antiresorptives. Time to antiresorptive initiation and its subsequent impact on the rate of SREs was analyzed using hazard ratios. A follow up, single-center retrospective study was conducted using EHR data with an emphasis on the identification of barriers to antiresorptive initiation. Here, descriptive, and inferential statistics were used to identify variables that have a statistically significant impact on antiresorptive initiation.ResultsA total of 759 patients with newly diagnosed MM met inclusion criteria for our multicenter study. Our study found that a delay in initiation of anti-resorptive therapy of greater than 31 days from diagnosis resulted in an increased risk for SRE with a hazard ratio of 1.654 (95% CI: 1.054-2.598; p-value = 0.029). In our follow up study, a total of 45.6% of patients with newly diagnosed MM were prescribed antiresorptive therapy, while 59% of patients with identified lytic lesions on screening imaging received anti-resorptive therapy. Statistically insignificant differences were observed in the time to initiation of anti-resorptive therapy based on health insurance. Variables such as race and gender were not found to have a statistically significant relationship with delays in antiresorptive initiation.ConclusionsPatients with NDMM should be initiated on antiresorptive therapy without delay to minimize the rates of SREs, and clinicians should be diligent in anticipating delays in initiation such as need for dental clearance and renal disease

Deep Supratentorial Extension is Associated with Poor Clinical Outcomes After Glioblastoma Resection

Introduction: Glioblastoma (GBM) often extends to deep supratentorial locations, which limits the extent of maximal safe resection. Deep supratentorial extension (DSE) may be a clinically convenient prognostic indicator following GBM resection. Methods: 582 GBM resections from 2012-2018 were retrospectively reviewed. DSE was defined as tumoral extension to the basal ganglia, thalamus, corpus callosum, internal capsule, hypothalamus, caudate, or putamen as identified on preoperative imaging. Results: DSE was identified in 32.9% cases (192), while 52.5% (306) involved only superficial supratentorial locations (frontal, parietal, temporal and occipital lobes). Within the DSE cohort, the most commonly affected anatomical locations were the corpus callosum (18.9%), basal ganglia (10.8%), and thalamus (5.5%). DSE was associated with a significantly higher rate of residual tumor (71.9%vs59.3%, p=.015), larger size (48.3 vs 43.6 mm, p=.007), and lower rate of radiological gross total resection (GTR) (55.6% vs 70.6%, p=.005). DSE was also associated with a worse progression free survival (PFS) (5.55vs8.32 months, p = .009) and overall survival (OS) (9.89vs14.23 months, p=.000). Kaplan-Meier curves showed worse OS with DSE (log rank=.003), and worse OS with involvement of 2+ DSE structures as compared to 1 or none (log rank=.000). DSE had no effect on OS among those achieving GTR (log rank=.626), but without GTR, DSE significantly worsened survival (log rank=.030) on Kaplan-Meier. Discussion: DSE portended higher rates of residual tumor, lower rates of GTR, and worse PFS and OS, particularly among those not achieving GTR and with involvement of 2+ structures. DSE in GBM is a convenient and reliable negative prognostic factor

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.</jats:p

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.</jats:p

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 lung cancer

Lung cancer is the leading cause of global cancer incidence and mortality, accounting for an estimated 2 million diagnoses and 1.8 million deaths. Neoplasms of the lungs are the second most common cancer diagnosis in men and women (after prostate and breast cancer, respectively). With increasing access to tobacco and industrialization in developing nations, lung cancer incidence is rising globally. The average age of diagnosis is 70 years old. Men are twice as likely to be diagnosed with lung cancer, which largely reflects differences in tobacco consumption, although women may be more susceptible due to higher proportions of epidermal growth factor receptor mutations and the effects of oestrogen. African American men in the US are at the highest risk of lung cancer. Family history increases risk by 1.7-fold, with a greater risk among first-degree relatives. Tobacco smoking is the greatest preventable cause of death worldwide, accounting for up to 90% of lung cancer cases, and continued consumption is projected to increase global cancer incidence, particularly in developing nations such as China, Russia, and India. Second-hand smoke among children and spouses has likewise been implicated. Radon from natural underground uranium decay is the second leading cause of lung cancer in the developed world. Occupational hazards such as asbestos and environmental exposures such as air pollution, arsenic, and HIV and Tb infection have all been implicated in lung carcinogenesis, while cannabis smoking, electronic cigarettes, heated tobacco products, and COVID-19 have been hypothesized to increase risk

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