2 Minute Medicine Rewind May 15, 2023

Analysis of Body Mass Index in Early and Middle Adulthood and Estimated Risk of Gastrointestinal Cancer

1. Individuals with an overweight or obese BMI are at increased risk for developing colorectal cancer and non-colorectal gastrointestinal cancers. 

Evidence Rating Level: 2 (Good)

Colorectal cancer (CRC) is the 5th most common cancer diagnosed in the United States. Though screening programs have improved the early detection and treatment of CRC, it remains an important public health concern. Obesity rates are rising globally, and obesity is a known risk factor for developing GI cancers. This retrospective cohort study used data from the Prostate, Lung, Colorectal, and Ovarian (PCLO) Cancer Screening Trial to investigate the association between BMI and the risk of developing CRC and non-colorectal GI cancers. The PCLO trial included participants aged 55 to 74, enrolled between November 8, 1993, and July 2, 2001. Analysis of the trial data initially occurred after 13 years of follow-up or December 2009, whichever came first, with the option to opt-in for further follow-up until December 2014. There were 135,161 participants included in the study population. 34,946 of these individuals were diagnosed with cancer during the trial, of which 5088 were GI cancers, including 2803 colorectal, 376 esophageal, 485 gastric, 348 liver, and 1076 pancreatic. Researchers determined that there was an increased risk of colorectal cancer for individuals with overweight BMI (HR, 1.23; 95% CI, 1.10-1.37) in early adulthood, overweight (HR, 1.23; 95% CI, 1.13-1.34) and obese (HR, 1.55; 95% CI, 1.38-1.75) BMI in middle adulthood, and overweight (HR, 1.21; 95% CI, 1.10-1.32) and obese (HR, 1.39; 95% CI, 1.25-1.54) BMI in later adulthood. They also found an increased risk of non-colorectal GI cancer associated with obese BMI (HR, 1.37; 95% CI, 1.04-1.80) in early adulthood, overweight (HR, 1.13; 95% CI, 1.03-1.24) and obese (HR, 1.44; 95% CI, 1.27-1.65) BMI in middle adulthood, and overweight (HR, 1.13; 95% CI, 1.03-1.24) and obese (HR, 1.36; 95% CI, 1.21-1.53) BMI in later adulthood. The researchers postulate that this relationship may be related to the state of chronic inflammation associated with increased BMI. Future research may assess whether weight loss is effective for reducing the risk of developing GI cancers for those with overweight or obese BMI at different stages of life. 

Presence of Fibroids on Transvaginal Ultrasonography in a Community-Based, Diverse Cohort of 996 Reproductive-Age Female Participants

1. The prevalence of uterine fibroids was found to be greater among reproductive-age participants of Black/ African American or Asian-Chinese descent compared to white participants.

Evidence Rating Level: 2 (Good)

Uterine fibroids are associated with significant morbidity, including heavy menstrual bleeding, pelvic pain, subfertility, and early pregnancy loss. The prevalence of uterine fibroids based on patient demographics, including ethnicity and age, has not previously been well defined. Researchers collected data from the University of California San Francisco Ovarian Aging Study, an ongoing longitudinal cohort study, to collect data on 996 females between 25 and 45 years of age. The cohort consisted of 23.0% Asian-Chinese, 25.0% Black or African American, 23.8% Hispanic or Latina, and 28.2% White participants. All participants were assessed via transvaginal ultrasonography. Fibroids were present in 35.7% (95% CI, 29.8%-42.0%) of Black or African American, 21.8% (95% CI, 16.7%-27.8%) of Asian-Chinese, 12.7% (95% CI, 8.7%-17.6%) of Hispanic or Latina, and 10.7% (95% CI, 7.3%-14.9%) of White participants (p < .001). Black or African American (adjusted OR, 4.72 [95% CI, 2.72-8.18]; p < .001) and Asian-Chinese participants (adjusted OR, 3.35 [95% CI, 1.95-5.76]; p < .001) were more likely to have fibroids, compared to White participants. Older age was also associated with an increased prevalence of uterine fibroids, with the greatest prevalence found at 40-45 years (adjusted OR, 6.18 [95% CI, 3.46-11.05]; p < .001). This assessment of fibroid prevalence among different populations is important for facilitating appropriate clinical suspicion and testing for this issue. Limitations of this study include the exclusion of patients with a history of prior pelvic surgery, which may lead to the underestimation of true fibroid prevalence. As well, all participants in the Asian ethnic group were Chinese, which is not truly representative of the diversity in Asian populations. 

Tumor–stroma ratio predicts prognosis and PD-L1 expression in hepatocellular carcinoma

1. The tumour stroma ratio (TSR) is a prognostic biomarker for predicting recurrence-free survival following hepatectomy for hepatocellular carcinoma. 

Evidence Rating Level:

Hepatocellular carcinoma (HCC) has a high morbidity and mortality burden worldwide. In this study, researchers aimed to assess the prognostic value of two biomarkers, the tumour stroma ratio (TSR) and PD-L1, in patients who had previously undergone hepatectomy for HCC. TSR is defined as the proportion of tumour cells to tumour stromal cells. The tumour stroma is known to influence tumour growth, invasion, and metastasis. PD-L1 is a biomarker, which is highly expressed by tumour stromal cells. In this study, researchers collected data from 95 participants from Xiangya Hospital, Central South University, China. All patients had undergone hepatectomy for HCC, with no previous non-surgical treatments. To quantify the TSR, they conducted a blinded assessment of pathology slides, with two examiners independently assessing each slide. PD-L1 expression was determined via immunohistochemistry. Participants were classified based on their TSR as stroma-high or stroma-low. The authors determined that recurrence-free survival (RFS) after liver resection was shorter in the stroma-high group compared to the stroma-low group, with mean RFS of 14.5 and 27 months respectively. They also found that PD-L1 expression was greater in the stroma-high group compared to the stroma-low group (p = .03). This study demonstrates that the TSR may be a useful biomarker for predicting recurrence-free survival after hepatectomy for HCC. Given that PD-L1 expression was found to be greater for the stroma-high group, the authors suggest that PD-L1 may be a useful therapeutic target for immunotherapy to improve clinical outcomes. A limitation of this study is the small sample size of 95 participants. Future research may assess the utility of TSR and PD-L1 as prognostic biomarkers in a larger cohort.  

Early sex-dependent differences in metabolic profiles of overweight and adiposity in young children: a cross-sectional analysis

1. Childhood overweight/adiposity at age 5 is associated with a specific profile of circulating metabolites, with a relationship that is more pronounced in girls than boys.

Evidence Rating Level: 2 (Good)

Over 340 million children and adolescents are overweight or obese worldwide, with increasing prevalence over time. Childhood obesity is a known risk factor for the development of cardiometabolic disease. Researchers aimed to assess serum metabolites associated with overweight/ obesity in childhood. They used data from the Canadian-based CHILD Cohort Study. Metabolite profiling was conducted for children at age 5 (n = 900) via multisegment injection-capillary electrophoresis-mass spectrometry. 45% of participants were female and 55% were male. They assessed the relationship between circulating metabolites and childhood overweight/ adiposity, defined as WHO-standardized body mass index ≥ 85th percentile and waist circumference ≥ 90th percentile, respectively. Data were assessed via multivariable linear and logistic regression, with sex-stratified analysis. The authors adjusted for the multiple confounding variables: nightly sleep hours, screen time, social disadvantage index, maternal education, breastfeeding status at 1 year, diet quality score, and physical activity level. They found that each standard deviation (SD) increment of glutamic acid, threonine, and oxoproline was associated with a 20-28% increased risk of overweight/adiposity, whereas the glutamine/glutamic acid ratio was associated with a 20% decreased risk. These associations were statistically significant in females, but not in males. This study determined that childhood overweight/ adiposity at age 5 is associated with a specific metabolic profile, which is more pronounced in girls than boys. Future research may address whether this metabolic profile is predictive of overweight/ obesity in adulthood. It also may be useful for future investigations of the metabolic pathways that contribute to childhood overweight/ obesity. 

Changes in Prescription Drug and Health Care Use Over 9 Years After the Large Drug Price Increase for Colchicine

1. The price increase of Colchicine in the United States led to greater use of alternative medications for gout treatment, as well as greater ED and rheumatology visits for gout. 

Evidence Rating Level:  2 (Good) 

Prices of prescription drugs have an important impact on the ability of patients to adhere to recommended medical treatments. The price of colchicine, a prescription medication used to treat gout, was increased in 2010 in the United States. This retrospective cohort study assessed MarketScan data from patients with gout and employer-based insurance between 2007 and 2019. The mean price of colchicine increased from $11.25 in 2009 to $190.49 in 2011, with the mean out-of-pocket cost increasing by 4.4-fold on average. The authors found that colchicine use declined following the price increase, with a 16.7% reduction in year 1 and a 27.0% reduction over the decade (p < .001). The use of allopurinol for gout treatment increased, with a 32% increase from baseline over the decade (p <0.001). Importantly, the authors found that from 2009-2019, ED visits for gout increased by 39.8% (p < .001), and rheumatology visits for gout increased by 10.5% (p <0.001). This study suggests that the cost of medications has a profound impact on medication choice, as well as the success of disease management. A limitation of this study is the exclusion of participants without employer-based insurance for drug coverage, given that this population is likely more impacted by changes to prescription medication costs.

Image: PD

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