Tuesday, February 7, 2023
Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)™
ABIM Diplomates - maximum of 0.25 ABIM MOC points
Nurses - 0.25 ANCC Contact Hour(s) (0 contact hours are in the area of pharmacology)
Pharmacists - 0.25 Knowledge-based ACPE (0.025 CEUs)
IPCE - 0.25 Interprofessional Continuing Education (IPCE) credit
This activity is intended for medical oncologists, dermatologists, gastroenterologists, internists, nurses, pharmacists, and other members of the health care team for patients with squamous cell carcinoma of the esophagus, head, and neck.
The goal of this activity is to describe the effect of alcohol intake and abstinence on acetaldehyde-induced DNA damage on the esophageal epithelium in individuals with aldehyde dehydrogenase 2 dysfunction, using a mouse model; the effect of direct acetaldehyde exposure on esophageal epithelial cells on inducing gene mutations; the effect of various risk factors on developing multiple dysplastic epithelium in the esophagus of patients with squamous cell carcinoma of the esophagus compared with cancer-free healthy subjects; and the effect of long-term alcohol and cigarette cessation on field cancerization, based on a Japanese cohort study and mouse model.
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CME / ABIM MOC / CE Released: 2/11/2022
Valid for credit through: 2/11/2023
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Alcohol and cigarette use are established risk factors for various cancers and act synergistically to increase esophageal squamous cell carcinoma (ESCC) and head/neck SCC risk. Field cancerization impairs patients' quality of life and survival, increasing risk for multiple cancers even after curative treatment. Alcohol and smoking cessation has an unknown effect on field cancerization risk.
Field cancerization and subsequent second cancer in patients with SCC were significantly associated with cigarette and alcohol use, based on data from more than 300 individuals.
Cigarette and alcohol use are established risk factors for SCCs of the esophagus, head, and neck, Manabu Moto, MD, from Kyoto University, Japan, and colleagues write. "In addition, squamous cell carcinoma...and squamous dysplastic epithelium develop multifocally in these organs," in a phenomenon known as field cancerization, but the interaction of multiple dysplastic epithelium with other factors--notably, whether cessation of cigarette and alcohol use would reduce risk for SCC--has not been well studied.
In a study published in Gastro Hep Advances, the researchers identified 331 adults with newly diagnosed superficial esophageal SCC who underwent endoscopic resection and 1,022 healthy control participants. Field cancerization was based on the number of Lugol-voiding lesions (LVLs) per endoscopic view according to 3 groups: grade A, 0 LVLs; grade B, 1-9 LVLs; or grade C, at least 10 LVLs. The primary study outcome was a measure of risk factors for the development of LVLs.
"Multiple LVLs are closely associated with inactive aldehyde dehydrogenase 2 (ALDH2) and field cancerization," the researchers note. Before assessing their human subjects, they used a mouse model to investigate whether alcohol intake and abstinence would affect acetaldehyde-induced DNA damage to the esophageal epithelium among individuals with ALDH2 dysfunction.
The researchers found that DNA damage, measured by acetaldehyde-derived DNA adduct levels (via N2-ethylidene-dG), accumulated with alcohol consumption over time, but decreased with alcohol cessation in the mouse model.
For the human part of the study, participants completed a lifestyle survey at entry, with questions about alcohol consumption history, alcohol flushing response, smoking, consumption of high-temperature foods, and consumption of green and yellow vegetables and fruit. Drinking status was divided into 5 groups: never/rarely (<1 unit/week), light (1-8.9 units/week), moderate (9-17.9 units/week), heavy (18 or more units/week), and ex-drinker, with 1 unit defined as 22 g ethanol. Smoking was divided into 3 groups: never (0 pack-years), light (< 30 pack-years), and heavy (30 or more pack-years). Patients were given educational materials at study entry about the importance of alcohol and smoking cessation, as well as verbal advice to cease these behaviors.
Participants underwent endoscopic surveillance at 3-month intervals for up to 6 months after endoscopic resection.
Overall, increased alcohol consumption was associated with increased risk in development of LVL across all LVL grades; higher grades of LVLs were positively associated with high-intensity alcohol consumption, smoking, flushing, and high-temperature foods, and negatively associated with eating vegetables and fruit.
The risk for LVL grade progression was most strongly associated with increased alcohol consumption and with reported flushing. "The greatest risk was observed in the patients with flushing reactions who consumed an average of 30 units per week in grade C LVL," with an odds ratio of 534, compared with healthy controls, the authors write. "Since flushing reaction is caused by accumulation of acetaldehyde due to ALDH2 [deficiency], our result also means that acetaldehyde is a strong carcinogen in field cancerization."
Secondary outcomes included the incidence of second primary esophageal SCC and head/neck SCC; these were significantly more prevalent in patients with grade C LVL (cumulative 5-year incidence of 47.1% for ESCC and 13.3% for head and neck SCC). However, alcohol and smoking cessation significantly reduced the development of second primary esophageal SCC (adjusted hazard ratios, 0.47 for alcohol and 0.49 for smoking).
The study findings were limited by several factors including the lack of randomization to noncessation and cessation groups and the inclusion of patients with cancer, but not long-term cancer survivors, the researchers noted.
"We believe that our data will be useful to establish a prevention and surveillance strategy for cancer survivors, because the overall prognosis of esophageal cancer and head and neck cancer is still poor," with a 5-year survival rate of less than 20%, and the results highlight the need to educate cancer survivors on the value of smoking and alcohol cessation, they added.
The study was supported by the National Cancer Center Research and Development Fund 36 by the Ministry of Health, Labour, and Welfare of Japan. The researchers have disclosed no relevant financial relationships.
Gastro Hep Advances. Published online October 21, 2021.[1]
