A 65-year-old man with a history of reflux disease experiences chest discomfort after undergoing an upper endoscopy for surveillance. The patient is hemodynamically stable and a gastrografin esophagram confirms a small contained perforation in the mid esophagus with minimal contamination in the mediastinum.
The most appropriate initial therapy consists of:
Correct Answer: C
Iatrogenic esophageal perforation can be a catastrophic complication of upper endoscopy. The incidence of perforation due to rigid endoscopy approaches 0.1% to 0.4% while that of flexible endoscopy varies from 0.01% to 0.06%. Perforation rates increase when additional interventions are performed such as balloon dilation. The timing of perforation is critical in managing the morbidity and mortality of this complication. Initial operative mortality rates approach 12% to 50%; however, a delay in management of 12 to 24 hours can significantly increase morbidity and mortality. The postoperative suture breakdown rate can reach 50% if repair is delayed beyond 24 hours.
Treatment of esophageal perforation requires multimodal therapy with intravenous antibiotics, nothing per mouth (NPO), isolating the area of the leak, and providing adequate nutrition either enterally via gastrostomy or intravenous therapy. Blind nasogastric tube insertion is discouraged as it may further damage the injured esophagus.
Hemodynamically stable patients with a contained perforation can be treated endoscopically with the placement of an esophageal stent to contain the leak and prevent further contamination. Depending on the location of the esophageal perforation, success rates with stent placement approach 80% to 90% in some series, allowing healing of the injured esophagus. Furthermore, stenting carries the lowest morbidity and mortality of all options available for treatment of esophageal perforation, challenging the old dogmatic teaching of primary repair as the “gold standard.”
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A 70-year-old woman undergoes upper endoscopy, which reveals a distal esophageal mass. Biopsy of the mass confirms adenocarcinoma with invasion into the mucularis propria. Whole body PET scan shows the distal esophageal mass with no lymphadenopathy and no distal metastases.
Which statement regarding treatment with chemoradiation therapy is most correct for this patient?
Esophageal adenocarcinoma (EA) is a highly lethal disease with a 5-year survival rate of approximately 10%. The ideal timing, treatment sequence, and dose of therapy remain an active area of investigation and controversy. Multiple studies have shown improved outcomes with the addition of neoadjuvant chemoradiation before surgical resection. This form of treatment has now become the standard approach in Europe and the United States for patients with locally advanced disease such as this patient with stage II disease (T2, N0, M0).
No current studies have definitively shown that the addition of radiation to chemotherapy improves overall survival over chemotherapy alone. Chemotherapy and radiation are each active against different forms of the cancer cell population with chemotherapy most effective against micrometastatic disease and radiation targeting the locoregional tumor mass. Esophageal perforation is a rare event after neoadjuvant chemoradiation occurring in less than 0.5% of patients evaluated.
A 60-year-old male with a history of coronary artery disease and Barrett disease completes a surveillance upper endoscopy. A 1-cm flat plaque is identified with pathology confirming low-grade dysplasia (LGD). Endoscopic ultrasound shows no lymphadenopathy and the tumor is confined to the mucosa.
What is an appropriate next step in treatment?
Correct Answer: D
BE is a premalignant condition with an increased risk of developing EA. Dysplasia continues to be the best clinically available marker of malignancy risk in patients with BE. In fact, the risk of progression for patients with nondysplasia is 0.2% to 0.5% per year but increases to 0.7% for patients afflicted with LGD and 7% in high-grade dysplasia. Definitive diagnosis of dysplasia can be challenging with slight variations in the interpretation of “indefinite for dysplasia” and LGD and thus requiring verification from a second pathologist with expertise in BE for confirmation of dysplasia. Patients with LGD should receive aggressive antisecretory therapy for reflux disease with a proton pump inhibitor to decrease changes associated with inflammation.
Current guidelines for management of LGD recommend annual surveillance with a protocol of four-quadrant biopsies at 1 cm intervals until two examinations in a row are negative for dysplasia, after which time surveillance intervals for nondysplastic BE can be followed. Six-month interval surveillance is advised for those with a diagnosis of “indefinite for dysplasia” who require further confirmation.
All other therapies are reserved for a locally advanced symptomatic disease rather than a tumor confined to the mucosa (Tis, N0, M0).
A 40-year-old man with a history of gastroesophageal reflux disease (GERD) undergoes esophageal sampling for Barrett esophagus (BE). An increase in the presence of which biomarker would indicate the presence of this condition?
BE is defined as intestinal metaplasia from squamous to columnar epithelium and is a risk factor for the development of EA. However, the majority of EA occurs de novo, and the prevalence of BE is reported to be between 1% and 8% calling into question the cost-effectiveness of routine endoscopy screening programs. Consequently, nonendoscopic methods for screening are also being employed. One method uses a device called a capsule sponge combined with an immunohistochemical biomarker (TFF3). The patient ingests the capsule that is attached to a string and contains a compressed mesh. The mesh is exposed when the gelatin capsule dissolves in the stomach. The mesh is then withdrawn through the esophagus where it collects samples of the cells lining the esophageal lumen. The biomarker is then used to differentiate Barrett epithelial cells from gastric columnar and esophageal squamous cells. An increase in the biomarker trefoil factor indicates an increase in columnar epithelium with intestinal metaplasia compared to normal esophagus. The expression of the biomarkers TFF1, FBP1, FMO5, and FOXA3 is increased in BE, but the levels are similar to those observed in the gastric mucosa.
A 60-year-old man with a history of heart failure with reduced ejection fraction (HFrEF), chronic obstructive pulmonary disease (COPD) requiring home oxygen, and GERD presents with dysphagia of solid and liquid foods, which has worsened over the last year. An esophagogastroduodenoscopy (EGD) is performed is performed, which reveals normal esophageal mucosa with negative biopsy results. High-resolution manometry reveals an integrated relaxation pressure of 20 mm Hg and a distal contractile integral (DCI <100 mm Hg/s/cm) of 100%. Esophagram demonstrates a dilated esophagus with poor emptying of barium.
Which of the following therapies would be the most appropriate for this patient?
Achalasia is a primary esophageal disorder with a pathologic consequence of degeneration of ganglion cells in the myenteric plexus of the esophageal body and the lower esophageal sphincter (LES) of unknown etiology. The degeneration leads to insufficient relaxation of the LES. Esophagraphy typically reveals esophageal aperistalsis with proximal dilation and minimal LES opening resulting in a “bird’s beak” appearance. At present, achalasia is incurable and management consists of palliation of symptoms. In patients who are felt to be good surgical candidates, laparoscopic myotomy with partial fundoplication is an effective strategy for long-term resolution of symptoms. However, in patients who are highrisk surgical candidates, initial treatment with graded PD is recommended. A prospective randomized multicenter European trial comparing graded PD to surgical myotomy in 200 patients revealed no difference in success rate after 2 years of follow-up (92% for PD vs 87% for surgical myotomy).
Complete 360-degree fundoplication would exacerbate the symptoms of dysphagia and is not an appropriate intervention for achalasia. Botulinum toxin is an attractive and user-friendly approach which interrupts the release of acetylcholine from presynaptic vesicles causing an interruption of a neurogenic component but has no effect on the myogenic component of the LES. Although the initial 1-month response rate is close to 75%, the therapeutic effect wears off and approximately 50% of patients relapse and require repeat treatment at 6- to 24-month intervals. POEM is a novel method of endoluminal myotomy performed by traversing the esophageal mucosa. Although the technique is promising, it requires advanced endoscopic skills. In addition, POEM has been shown in 50% of patients to promote further acid reflux.
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