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Photodynamic Therapy for Barrett’s Esophagus - An Overview

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Photodynamic therapy is an alternative to esophagectomy in Barrett’s esophagus. Read the article to know more.

Medically reviewed by

Dr. Vasavada Bhavin Bhupendra

Published At October 6, 2023
Reviewed AtFebruary 26, 2024

Introduction

Barrett’s esophagus is a premalignant condition. In this condition, the cells lining the esophagus are altered. This is commonly seen in people with gastroesophageal reflux disease (GERD), though it is also observed in people without GERD. Frequent heartburn and acid regurgitation (backward flow of the stomach acid) are the common symptoms of Barrett’s esophagus. Esophagectomy is the standard mode of treatment for high-grade dysplasia Barrett’s esophagus. Photodynamic therapy is a minimally invasive alternative to the surgical approach for Barrett’s esophagus. A total cure for Barrett’s esophagus is not yet found. Since it has a chance of recurrence, frequent monitoring is essential.

What Is Photodynamic Therapy?

Photodynamic therapy is a minimally invasive endoscopic procedure that destroys target cells using light of a specific wavelength acting on a photosensitizing agent. It has been used in Europe, North Africa, and Japan in treating neoplasms of the esophagus and dysplastic Barrett’s esophagus.

In this method, a photosensitizing drug is given to the patient, followed by the application of light to bring about cell damage. Hematoporphyrin derivative (HpD) is the commonly used photosensitizer. Another approach includes the use of sodium porfimer and red light. Another novel approach is endogenous photosensitization using aminolevulinic acid (ALA). ALA is a naturally occurring product in the heme synthesis pathway. The compound, as such, has no photosensitive properties, but on metabolizing to protoporphyrin IX (PpIX), it becomes photosensitive. Using PpIX has many advantages over HpD. A shorter duration of photosensitization, increased affinity towards epithelial cells, and lesser damage to the underlying tissues are added advantages.

How Does Photodynamic Therapy Work?

Photodynamic therapy is a minimally invasive procedure where the photoactivation of a photosensitizing drug is done by using light of an appropriate wavelength. The two compounds interact in the presence of oxygen to produce highly active and short-lived cytotoxic substances like singlet oxygen and free radicals. A cytotoxic substance is a medicine that contains chemicals that are harmful to cells, inhibit their replication, and are used in treating conditions like cancer. These cytotoxic substances cause oxidative damage to cell organelles and vascular toxicity, which promotes the death of the required tissue.

Photodynamic therapy using sodium porfimer has a penetration of three to four millimeters, while using ALA, the penetration depth is less than two millimeters. Studies reveal that the depth of Barrett's mucosa would not exceed 0.6 mm, and subsequent penetration is not required to get rid of high-grade dysplasia.

What Are the Advantages of Photodynamic Therapy?

The advantages of photodynamic therapy include selective targeting of the malignant or affected tissue, no interaction between systemic forms of cancer therapies with photodynamic therapy, and minimal intervention. Relatively low morbidity and toxicity are associated with the therapy. Another advantage of the procedure is that it is minimally invasive and can be done as an outpatient procedure. The mortality rate is nil.

What Are the Disadvantages of Photodynamic Therapy?

The intestinal columnar epithelium persists beneath the non-squamous epithelium even after photodynamic therapy. This is considered a disadvantage of the therapy. Another study revealed that a minor group of people, about three percent, developed squamous cell carcinoma after photodynamic therapy. Hence, every patient undergoing the therapy should be in constant review with multiple biopsies after the treatment. Another observation is the recurrence of the condition in 17 percent of people after photodynamic therapy. Another interesting study point is that the recurrence was located close to the gastroesophageal junction. This cloud is probably due to the difficulty in applying light properly in this area. The gastroesophageal junction is an area prone to frequent episodes of acid attacks. Hence, inflammation of the area is frequent. This can also reduce the success rate of photodynamic therapy.

How Is Barrett's Esophagus Diagnosed?

The diagnosis and evaluation of Barrett's esophagus involve using any of the following methods:

  • Esophagogastroduodenoscopy (EGD): Barrett’s esophagus is best diagnosed via esophagogastroduodenoscopy (EGD).

  • Biopsy: A biopsy is necessary to confirm the diagnosis of Barrett's esophagus.

  • Ultrasonography: Endoscopic ultrasonography (EUS) should be performed to assess surgical resectability in cases of malignancy discovered during surveillance endoscopy.

What Are the Treatment Alternatives to Photodynamic Therapy?

The following are some other options for managing high-grade dysplasia:

  • Surveillance endoscopy and thorough biopsy every three months till malignancy is found

  • Endoscopic Ablation: Ablation is the first-line treatment in the majority of large hospitals.

  • Surgical Resection: Research has demonstrated that surgery is effective in managing symptoms of gastroesophageal reflux disease (GERD); however, there is insufficient data to suggest that surgery treats Barrett esophagus regression.

  • Other ablative therapies under investigation include thermal photocoagulation using neodymium-yttrium aluminum garnet (Nd: YAG) laser, argon beam plasma coagulation (APC), electrocoagulation, EMR (electronic medical record), etc. They are developed as alternatives to surgery and yield good results. In these techniques, the cancerous areas or the area of interest should be detected first, and then ablation should be targeted to these areas. Nd: YAG laser is used to ablate the mucosa in Barrett’s esophagus that is left behind after the photodynamic therapy. This has been seen to yield good results.

  • Proton pump inhibitors (PPIs) are used to reduce gastric acid secretion.

What Are the Side Effects and Risks Associated With Photodynamic Therapy?

The side effects and risks associated with Barrett’s esophagus include;

Other complications that were seen in a minor population after photodynamic therapy include;

  • Atrial fibrillation is a rapid heart rhythm resulting in the formation of blood clots in the heart.

  • Photosensitivity reaction.

  • Esophageal perforation.

  • Pleural effusion (abnormal accumulation of fluid in the pleural cavity).

  • Esophageal strictures are abnormal narrowing of the lumen of the esophagus.

Side effects like chest pain, nausea, vomiting, and dysphagia were found to be transient and under control with medication. 36 percent of the strictures were rectified with dilation. The strictures were associated with the type of delivery of photodynamic therapy. Photosensitivity was the main drawback of photodynamic therapy with sodium porfimer. Lesions similar to sunburn were observed on the skin of the face, neck, and hands. A major portion was resolved by itself without any medications. Patients undergoing photodynamic therapy with sodium porfimer must avoid the sun and other bright light for thirty to ninety days. They must take precautions to protect their skin and eyes. This must be reinforced by proper patient education.

Conclusion

Photodynamic therapy was the main ablation method used in Barrett’s esophagus for many years. It is a reliable and safe method for eliminating dysplasia. The advantage of the procedure includes selective targeting of the affected cells with minimal strictures and perforations. However, the procedure is less used these days due to its significant drawbacks. The drawbacks include the requirement to administer the agents through IV (intravenous) and the extended duration of photosensitivity. Long-term endoscopies should be done regularly to check for recurrence or any progression to malignancy. It can also be used to detect residual tissues of Barrett’s esophagus. Proper patient education is inevitable to reduce photosensitivity reactions and manage the side effects.

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Dr. Vasavada Bhavin Bhupendra
Dr. Vasavada Bhavin Bhupendra

Surgical Gastroenterology

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barrett's esophagusphotodynamic therapy
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