Achalasia is a rare esophageal motility disorder that leads to difficulty swallowing and other symptoms. It is characterized by loss of esophageal peristalsis and impaired lower esophageal sphincter (LES) relaxation.¹ Achalasia is associated with an increased risk of esophageal cancer, as first noted by Fagge² in 1872. The incidence of esophageal cancer in patients with achalasia is higher than that in the general population, even though the absolute risk is low.^3,4 Nevertheless, surveillance endoscopy is not recommended for patients with achalasia owing to this rarity.⁵

High-resolution manometry (HRM) and minimally invasive peroral endoscopic myotomy (POEM) can assist in diagnosing and treating achalasia. On the other hand, the safety and efficacy of POEM and endoscopic submucosal dissection (ESD) in achalasia with synchronous esophageal cancer have not been investigated.⁵

This paper reports a case of achalasia with synchronous esophageal cancer that was successfully treated with concomitant ESD and POEM.

A 72-year-old man presented to the emergency department with worsening dysphagia that had started the previous day. He was administered amlodipine for hypertension, teneligliptin and metformin for type II diabetes mellitus, and ezetimibe and rosuvastatin for dyslipidemia. He had experienced recurrent dysphagia for five years and was referred to the authors’ department for dysphagia when he had been hospitalized for empyema three years prior. The symptoms persisted for two months. Therefore, HRM was performed, and the patient was diagnosed with type I achalasia. He was treated with pneumatic balloon dilation; his symptoms improved, and he was followed up on an outpatient basis.

Despite outpatient follow-up, the patient's dysphagia symptoms had recently worsened, prompting a visit to the emergency department for a comprehensive evaluation to determine the underlying cause. A Chest CT on the day of hospital admission revealed a dilated esophagus and residual food. Upper gastrointestinal endoscopy was performed the following day, but a detailed observation was not possible because of the food residue (Fig. 1A). After fasting for two days, upper GI endoscopy was repeated, and the food residue was removed endoscopically (Fig. 1B, D). Subsequently, a detailed upper GI endoscopy revealed a well-demarcated, erythematous depressed lesion, approximately 15 mm in size, at the posterior side of 33cm from the incisor (Figs. 1C, 2A), along with vascular changes on the narrow band image (Fig. 2B). A histology examination confirmed the carcinoma. Subsequently, HRM was performed and showed elevated integrated relaxation pressure (IRP) over 15 mmHg. No contractile activity of the esophageal body was identified, indicating type I achalasia (Fig. 3A). A timed barium esophagogram revealed a bird's beak sign on the esophagogastric junction, a dilated esophageal body, and a sigmoid- like appearance (Fig. 3C). Esophageal transit scintigraphy demonstrated a prolonged esophageal transit time with 99% of the food remaining after 10 minutes (Fig. 3B).

Neck CT, abdominal and pelvic CT, and PET-CT were performed to evaluate superficial esophageal cancer and type I achalasia. No metastatic findings were observed. Endoscopic ultrasonography revealed cancer confined to the mucosa and mild thickening of the esophageal smooth muscle layer.

After consultation with the patient and his family, ESD for esophageal cancer (Fig. 2) and POEM for achalasia (Fig. 4) were performed simultaneously. First, ESD was performed at 32–35 cm from the incisor, and the resected specimen was approximately 3 cm in diameter. Subsequently, a mucosal incision for the POEM entry site was made at 39 cm from the incisors. Submucosal tunneling continued to the gastric cardia, which was 48 cm from the incisors, and myotomy was performed from 42 cm to 48 cm from the incisors without perforation around the LES (4 cm on the esophagus side and 2 cm on the gastric cardia side). The ESD and POEM run times were 61 and 49 minutes, respectively. Esophagography was per formed to assess the POEM opening site and esophagogastric junction for leakage; no abnormalities were found. The patient was discharged without any other complications after the diet was started. Subsequent histology confirmed a well-to-poorly differentiated squamous cell carcinoma (11 mm×8 mm) with high-grade dysplasia (10 mm×9 mm) confined to the lamina propria of the mucosal layer with clear margins. Despite discussing additional treatment because of the poor differentiation, the pathological review revealed only a small portion of poorly differentiated tissue. In addition, the patient and his family refused further therapeutic interventions. Consequently, the patient underwent regular follow-up with endoscopy and other imaging modalities. The patient was followed up for one year with no recurrence of esophageal cancer, increased IRP on HRM, or symptoms of dysphagia.

Achalasia is caused by the loss of the inhibitory ganglion in the myenteric plexus of the esophagus. In the initial stage, degeneration of the inhibitory nerves results in the unopposed action of excitatory neurotransmitters, resulting in non-peristaltic contractions. The progressive loss of cholinergic neurons results in dilation and a lower contraction amplitude in the esophageal body.⁶

Oral pharmacological therapy, botulinum toxin injection, pneumatic balloon dilatation, POEM, and laparoscopic Heller’s myotomy provide effective results for achalasia by relieving symptoms, such as dysphagia and related complications. Laparoscopic Heller’s myotomy is a first-line treatment for achalasia that can achieve excellent outcomes but is invasive. Recently, POEM has gained popularity as a commonly used treatment for achalasia. Recent guidelines show that POEM has similar outcomes to laparoscopic Heller’s myotomy.⁷

In patients with suboptimally treated or untreated achalasia, food residue and fluid in the esophageal body can result in bacterial overgrowth and chemical irritation. This leads to chronic hyperplastic esophagitis and malignant transformation of esophageal epithelial cells into esophageal squamous cell carcinoma.⁴ In addition, effective treatment of achalasia can lead to sphincter insufficiency, resulting in gastroesophageal reflux disease and Barrett’s esophagus (BE). Esophageal adenocarcinoma can develop after BE but is less common than squamous cell carcinoma.³

As a modality for superficial esophageal cancer, ESD has evolved into a viable treatment because of its equivalent long-term survival outcomes to surgical resection.^8,9 The simultaneous detection and endoscopic treatment of achalasia and esophageal cancer is rare. Few cases where achalasia and superficial esophageal cancer were treated simultaneously have been reported (Table 1).^10,11 In one case, concurrent chemoradiotherapy was performed on a patient with achalasia and advanced esophageal cancer.¹² In other cases, ESD for esophageal cancer was performed either before or after POEM for achalasia rather than at the same time.⁵ This paper reports the successful endoscopic treatment of concomitant achalasia and superficial esophageal cancer.

In a multicenter study in Japan by Sato et al.⁵, multivariate analysis revealed the risk factors for the development of esophageal cancer in achalasia, including disease duration, age at diagnosis, male sex, alcohol consumption, smoking status, and sigmoid-type achalasia. Of 43 esophageal cancer cases, 31 (72.1%) were identified during screening for a one-year follow-up after POEM. Regarding an endoscopic resection for superficial esophageal cancer, the en-bloc resection rate for cases in which cancer was detected before POEM was 95.8% (46/48), and 89.3% (25/28) for cases detected after; these results were not significant (p=0.351). Hence, ESD is feasible for achalasia, even though it is challenging along the POEM-line, as three patients had esophageal cancer on the POEM-line. Two patients underwent ESD. One underwent a piecemeal resection because of submucosal fibrosis, and the other underwent surgery because ESD was difficult due to severe fibrosis.⁵

Therefore, performing ESD and POEM simultaneously may reduce the burden of general endotracheal anesthesia (GETA) procedures twice¹³ and reduce the risk of fibrosis resulting from performing ESD or POEM first. Achalasia and esophageal cancer can be treated concurrently if they are located in different regions. In the present case, the esophageal cancer lesion was determined to be in the middle of the esophagus (33 cm from the incision in the dilated esophagus), and the morphology of the achalasia was a stretched and rotated sigmoid. Hence, the opening for the ESD and POEM was more than 4 cm apart. Consequently, ESD was feasible without any hindrance to the POEM procedure. On the other hand, depending on the priority and symptoms between the two treatments, sequential treatment should be considered if the lesion is located in an area that may affect the POEM procedure. In addition, other options, such as chemoradiotherapy for esophageal cancer in conjunction with POEM, may also be considered.

This paper reports a case in which superficial esophageal cancer was identified at the time of achalasia diagnosis and was treated successfully with simultaneous ESD and POEM. Although achalasia increases the risk of esophageal cancer, endoscopic surveillance is controversial regarding its cost-effectiveness.¹⁴ On the other hand, regular screening for esophageal cancer is essential for patients with achalasia.¹⁵ Food retention is a known risk factor for esophageal cancer in patients with achalasia. Therefore, it is essential to thoroughly remove the food and closely monitor the esophageal mucosa from diagnosis.