Abstract
We have made it to our fourth year of Foregut! We have published expert opinions and reviews on a myriad of foregut topics from achalasia to adenocarcinoma. A couple of our recent themed issues have been focused on broader topics including healthcare disparities and on global surgery. This issue of Volume 4 contains several invited pieces on a global cancer challenge uniting previous themes. The incidence of esophageal cancer is anticipated to increase to nearly a million cases globally by 2040, per GLOBOCAN data, 1 and we anticipate the predominance of esophageal squamous cell carcinoma (ESCC) will continue with current proportion at ~85%. The poor outcome of ~20% five-year overall survival persists and the problem and lack of progress may continue for several reasons. The topic of ESCC significantly impacts low-to-middle income populations domestically and globally and is associated with nascent delivery of screening modalities and early detection. We know that risk factors for ESCC include tobacco, alcohol, environmental factors including poverty and things consumed including but not limited to pickled vegetables, extremely hot (>70°C) beverages and betel nut. Most of these are modifiable risk factors. We know that when ESCC is detected early, there are ways to treat it endoscopically. This is a global oncologic problem. What are the solutions?
In this issue of Volume 4 of Foregut, we are treated to food for thought to create potentially actionable items. We learn about the epidemiology of ESCC, endoscopy and screening modalities as well as the role of esophagectomy for multifocal dysplasia. We also learn that we still have many more questions to answer on early detection, management, and scientific pursuit of preventable causes.
Invited author Sheraz Markar reminds us of the high incidence in specific geographic regions: the Asian belt and East African corridor as well South American Gaucho area but also in some higher income regions including Eastern Europe and Japan. Why are the populations of these areas at high risk? Five general categories: smoking, alcohol, diet, environment, and infection. What are potential areas of investigation? Understanding more about the tumor biology including the role of human papilloma virus, genetics of ESCC transformation and environmental factors.
What can do to address the low rates of early detection? As a native of a high-volume country for ESCC, Sabita Jiwnani summarizes well the need for screening: Dr. Jiwnani summarizes established screening criteria for disease with a high incidence: (1) Need for a validated test for early detection, (2) Detectable preclinical phase [so we can take action], (3) Effective treatment option at an early stage. 2 China has had several clinical trials of investigation as summarized by Dr. Jiwnani. Screening is an approach to reducing mortality. In China they have established risk factors and endoscopic screening programs to combat this oncologic disaster. They are leaders in screening for ESCC but have used primarily endoscopic approaches. There is screening with the balloon cytology approach but again it has not been validated and it is not always patient-friendly.
In the submission by Sharmila Anandasabapathy and Shaleen Vasavada, we learn of the advanced endoscopic approaches for targeting where to biopsy with use of widely available narrow-band imaging (NBI) and less applied Lugol’s chromoendoscopy, while they share with us details of blue laser imaging (BLI)—more sensitive than white-light and NBI. And then there is confocal laser endomicroscopy (CLE), high-resolution microendoscopy (HRME), and fancy scanning technology, like i-SCAN and—of course—artificial intelligence techniques. The advantages of this technique of CLE include reliable distinction between normal esophageal mucosa and ESCC; however, they would not be broadly applicable to wide swaths of the populations at risk—the people who have portable medical records and who smoke or chew betel nut.
In order to provide a solution in the global cancer arena, we need least invasive approaches to identify premalignant or malignant lesions, so they can be broadly applied when it is confirmed the techniques have high rates of accuracy. Endoscopic screening can be sensitive but costly. Noninvasive screening with balloon or sponge is more cost-effective but has not been validated in large studies.
How do we reduce predicted incidence of >900 000 cases of esophageal cancer globally by 2040?
(1) Public health measures: awareness about dangers of betel nut chewing and consumption, global anti-smoking campaigns, awareness re: risks of ethanol consumption, (2) Identify high-risk populations for screening: aforementioned in (1) and also those with history of head and neck cancer, alcoholic cirrhosis, alcoholic pancreatitis. (3) Initiate clinical trials with the less invasive screening modalities, so they may be validated and applied globally. The balloon, the swallowed sponge on a string. Get innovative. (4) Collaborate- this is an opportunity to investigate on the global platform. Go global. (5) If we continue to focus on endoscopic therapies in our high-income countries, then we will contribute to the outcome divide. In high-income countries overall survival of EC is not great—20% but in low-income countries where the risk factors are rampant, the survival is only ~5%. Until we have a less invasive modality to detect ESCC at an early stage in an identified high-risk population, we won’t be making significant forward progress. This is a big problem in need of big solutions.
Finally go back to the bench and do deeper dives into these hypotheses: (1) human papilloma virus is a cause of ESCC but what’s the biology? (2) Are there some patients with multifocal squamous dysplasia who should get an esophagectomy and not repeated endoscopic resections and ablations?
SCC—Screen and Detect to Endoscopically Resect. That’s one path to improving outcomes for all!
Thank you to the contributors of the invited reviews as well as the original research. We continue to receive in increasing volume as we move forward with Foregut in this fourth year.