GASTROINTESTINAL MOTILITY AND FUNCTIONAL BOWEL DISORDERS, SERIES #25

Richard W. McCallum, MD, FACP, FRACP (Aust), FACG, AGAF Revisiting Achalasia and Esophageal Squamous Cell Carcinoma

Fernando Moran Cong Phan Richard W. McCallum

INTRODUCTION chalasia is a rare, chronic esophageal unclear. Treatment aims at lowering the lower motility disorder with an estimated annual esophageal sphincter (LES) pressure to improve Aprevalence of 1 per 100,000 subjects in the passage of food. Even after treatment there the western populations. The disease can occur is continued aperistalsis and delayed transit, so at all ages but the incidence increases with age.1 sufficient symptom control does not prevent Achalasia results from progressive degeneration patients from having persistent retention of foods of ganglion cells in the of the and fluids in the . This is associated with of the lower esophageal sphincter degrees of bacterial degradation of the retained and the lower two-thirds of the esophagus, resulting contents and impaired clearance of regurgitated in failure of relaxation of the lower esophageal acid gastric contents. These factors can result in sphincter, accompanied by a loss of in chronic inflammation of the esophageal mucosa, the distal esophagus.2 Predominant symptoms are which potentially increases the risk of development and regurgitation. Treatment is purely of hyperplasia, dysplasia, and esophageal . In symptomatic as the etiology of achalasia is still addition, lowering of LES pressure does facilitate chronic acid gastroesophageal reflux which in Fernando Moran, MD, Cong Phan, Richard W. a small percentage of patients leads to Barrett’s McCallum, MD, FACP, FRACP (AUST), FACG, metaplasia and adenocarcinoma.1 Currently there AGAF, Professor of Medicine and Founding Chair, are no specific guidelines for cancer surveillance Division of , Director, Richard W. in long term follow up of patients with achalasia. McCallum, MD, FACP, FRACP (AUST), FACG, AGAF, Professor of Medicine and Founding Case Report Chair, Division of Gastroenterology, Director, A 58 year-old Caucasian male presented with Center for Neurogastroenterology and GI Motility, dysphagia. He had the history of heavy alcohol Texas Tech University Health Sciences Center, use (four drinks daily for 35 years). Previously Paul L. Foster School of Medicine, El Paso, TX (continued on page 32)

30 PRACTICAL GASTROENTEROLOGY • JULY 2018 Revisiting Achalasia and Esophageal Squamous Cell Carcinoma GASTROINTESTINAL MOTILITY AND FUNCTIONAL BOWEL DISORDERS, SERIES #25

(continued from page 30) diagnosed with achalasia, he underwent pneumatic balloon dilation in 2012. He experienced an esophageal perforation requiring an open repair and myotomy without any accompanying fundoplication. After surgery, he experienced constant reflux but no achalasia symptoms. He was started on a proton pump therapy immediately after surgery. He noticed and difficulty in July 2017, with a 20-pound weight loss and progressive dysphagia to solid food, unable to tolerate anything but a pureed diet. On physical examination the patient had facial thinning, firm hepatomegaly and scoliosis. There were no Virchow lymph nodes palpable in the neck. His laboratory evaluation was unremarkable, Figure 1. A tight stricture with a suggestion of “shouldering” including albumin and hemoglobin. Liver enzymes in the proximal esophagus about 15 cm above the were also within normal limits. gastroesophageal junction Barium swallow with a 13 mm barium tablet revealed a tight stricture with a suggestion of to a 17mm diameter size in preparation for the “shouldering” in the proximal esophagus, 15 cm initiation of the radiation treatment. In addition, proximal to the gastroesophageal (GE) junction, and a percutaneous gastrostomy tube was placed to delay of the barium tablet at the stricture (Figure 1). ensure adequate nutrition maintained through the Distal to the stricture there were no radiographic treatment course/ findings of achalasia. Upper revealed that the upper third of the esophagus was normal. Discussion A stricture was found 25 cm from the incisors and has been a very infrequent the endoscope would not pass (Figure 2). Savary complication in the long term follow up of achalasia. dilation was performed at 7 mm, 9 mm, 11 mm Among a large case series, it ranges from 0.4% to and 14 mm. The endoscope could then traverse 9.2%.3 One review found that the prevalence of the stricture after dilation. The stricture extended esophageal cancer in achalasia was 3% in the long from 25 to 35 cm from the incisors. Its mucosa was term follow up (five to 20 years), corresponding to nodular, friable, irregular and polypoid, suspicious a 50-fold increased risk.4 Most cases of esophageal for esophageal cancer (Figure 3). of cancer in patients with achalasia are squamous stricture showed moderately differentiated cell carcinoma located in the middle third of the squamous cell carcinoma. The biopsies of the esophagus. It is proposed that, although improved esophagus distal to the stricture showed changes symptomatically by medical or surgical therapies, of reflux but no Barrett’s esophagus. there is continuing stasis of food in the esophagus Subsequent computed tomography (CT) promoting lactic acid production and fermentation, imaging of the chest revealed a circumferential, inducing slow and continuous damage to the mass-like thickening of the proximal esophagus, esophageal mucosa.5,7 Conversely, adenocarcinoma approximately 7.5 cm in length. There was a loss may occur after treatment for achalasia, almost of the fat plane with the aortic arch, proximal invariably arising from Barrett’s esophagus due ascending aorta, lower trachea and left mainstem to longstanding gastroesophageal reflux.7 Alcohol bronchus, concerning for tumor infiltration. There use also places patients at higher risk for squamous were no pulmonary nodules but a couple of small cell cancer. A combination of the factors described mediastinal lymph nodes were noted (Figure 4). above along with the long history of alcohol abuse The patient was referred for chemotherapy and may have been the main triggers for squamous cell radiation. The was re-dilated carcinoma.

32 PRACTICAL GASTROENTEROLOGY • JULY 2018 Revisiting Achalasia and Esophageal Squamous Cell Carcinoma GASTROINTESTINAL MOTILITY AND FUNCTIONAL BOWEL DISORDERS, SERIES #25

Figure 2. Initial endoscopic views of the stricture in the proximal esophagus.

Figure 3. Endoscopic view of the stricture following dilation with the Savary technique notes the irregularity and nodularity of the stricture. (Friability secondary to the dilation)

Currently there are no guidelines for for Barrett’s esophagus improve survival to 73– monitoring squamous cell carcinoma or other 85% within two years of diagnosis.11 One other late complications such as esophageal and peptic consideration is the large cost of such surveillance stenosis or .6 Whether surveillance programs. One study in 1995 has estimated that endoscopy should be generally recommended about 732 endoscopic procedures were needed to for all patients with esophageal achalasia is still detect three over a 15-year study period controversial due to the long interval between the costing $585,000 thus averaging $195,000 per initial symptoms and diagnosis of achalasia and the cancer detected.12 This is contrasted to $31,000 in development of carcinoma.8 Studies have indicated similar adenocarcinoma surveillance program for an interval between the diagnosis and treatment of patients with Barrett’s esophagus.12 On the other achalasia and the diagnosis of esophageal cancer hand, its proponents for surveillance argue that of at least 15 years.9,10 Its opponents contend that, without strict endoscopy surveillance, esophageal even under surveillance, mortality from esophageal malignancies will be detected very late and in an cancer in achalasia patients resembles the general advanced stage. This is thought to be due to residual population with a survival rate of 40% after year two dysphagia which can mimic esophageal cancer and of diagnosis1 while similar surveillance programs recurrent achalasia.13 In a recent study in 2016, Ota

PRACTICAL GASTROENTEROLOGY • JULY 2018 33 Revisiting Achalasia and Esophageal Squamous Cell Carcinoma GASTROINTESTINAL MOTILITY AND FUNCTIONAL BOWEL DISORDERS, SERIES #25

Figure 4. CT scan of the chest: Esophagus: There is a circumferential mass like thickening of the mid esophagus measuring up to 2.3 cm in maximum thickening and over a length of approximately 7.5 cm. There is mild stagnation of the contrast in proximal dilation of the esophagus without complete obstruction. There is loss of the fat plane between the thickened esophagus and the medial portion of the aortic arch and anterior wall of the proximal ascending aorta without evidence of intraluminal filling defects. In addition, anteriorly the mass is adherent to the lower trachea above the tracheal bifurcation on the left side and posterior wall of the left mainstem bronchus. These latter observations raise concern for the possibility of local invasion by the esophageal cancer. et al. performed annual follow-up in 32 endoscopy results, barium swallow and patients over a mean period of 14 years (range 5-40 other known independent risk factors for squamous years) after successful achalasia surgery treatment. cells carcinoma such as age, alcohol, tobacco use They were able diagnose 6 of 32 patients with and male gender. In high risk patients, we should esophageal cancer at early stage. All six patients consider endoscopy with biopsy beginning within were alcoholic drinkers and three had smoking five years after diagnosis and possibly every three habit.14 This suggests follow-up endoscopy with to five years thereafter. biopsy is important in early cancer diagnosis as the risk for malignant transformation still persist Take Home Messages even after successful achalasia treatment. When following patients who have been treated Overall, we suggest to identify a risk for achalasia, the initial treatment is key. It is assessment profile score in individual achalasia expected that after pneumatic dilation there may be patients based on the type of treatment they recurrence of dysphagia and repeated pneumatics initially underwent, esophageal pH data, previous over the next five to 20 years. With a successful myotomy and partial fundoplication there should be minimal or no recurrence of the achalasia. PRACTICAL However, when the myotomy surgery is incomplete, typically because the myotomy GASTROENTEROLOGY is not extended at least 2cm into the , recurrence of “achalasia” dysphagia will occur within the first one to two years. When there is no Visit our Website: fundoplication accompanying the then the scenario for complications of long term practicalgastro.com reflux are also in the equation, specifically a peptic stricture as witnessed in our case. Finally, there

34 PRACTICAL GASTROENTEROLOGY • JULY 2018 Revisiting Achalasia and Esophageal Squamous Cell Carcinoma GASTROINTESTINAL MOTILITY AND FUNCTIONAL BOWEL DISORDERS, SERIES #25 remains a background incidence for squamous 7. Devault K. Risk of Esophageal Adenocarcinoma in cell esophageal cancer in all patients, particularly Achalasia Patients, a Retrospective Cohort Study in Sweden. Yearbook of Gastroenterology. 2011;2011:4-5. with age, heavy alcohol intake and or cigarette doi:10.1016/j.ygas.2011.07.066. smoking. The bottom line is to be aware of the 8. Park JC, Lee YC, Kim SK, et al. Achalasia Combined with different possibilities in the long-term follow-up Esophageal Cancer Treated by Concurrent Chemoradiation of achalasia patients. Therapy. Gut and Liver. 2009;3(4):329-333. doi:10.5009/ gnl.2009.3.4.329. 9. Achalasia and esophageal cancer: incidence, prevalence, References and prognosis. Brücher BL, Stein HJ, Bartels H, Feussner H, Siewert JR World J Surg. 2001 Jun; 25(6):745-9. 1. Long-Term Esophageal Cancer Risk in Patients With 10. Achalasia complicated by oesophageal squamous cell car- Primary Achalasia: A Prospective Study I Leeuwenburgh-P cinoma: a prospective study in 195 patients. Meijssen MA, Scholten-J Alderliesten-H Tilanus-C Looman-E Tilanus HW, van Blankenstein M, Hop WC, Ong GL Gut. Steijerberg-E Kuipers - The American Journal of 1992 Feb; 33(2):155-8 Gastroenterology – 2010 11. Corley D, Levin T, Habel L, Buffler P. Association between 2. Stuart J Spechler, MD. Achalasia: Pathogenesis, clinical surveillance and survival in Barretts adenocarcinomas: A manifestations, and diagnosis. Uptodate. Feb 09, 2018. population-based study. Gastroenterology. 2001;120(5). 3. O’Neill OM, Johnston BT, Coleman HG. Achalasia: a doi:10.1016/s0016-5085(01)80082-2. review of clinical diagnosis, epidemiology, treatment and 12. Streitz JM, Ellis FH, Gibb SP, Heatley GM. Achalasia and outcomes. World J Gastroenterol 2013;19:5806–12. squamous cell carcinoma of the esophagus: Analysis of 241 4. Dunaway PM, Wong RK. Risk and surveillance intervals patients. The Annals of Thoracic Surgery. 1995;59(6):1604- for squamous cell carcinoma in achalasia. Gastrointest 1609. doi:10.1016/0003-4975(94)00997-l. Endosc Clin N Am 2001;11:425–34. 13. Ribeiro, U. , Posner, M. C., Safatle-Ribeiro, A. V. and 5. Achalasia: a risk factor that must not be forgotten for Reynolds, J. C. (1996), Risk factors for squamous cell esophageal squamous cell carcinomaS. Rios-Galvez-A. carcinoma of the oesophagus. Br J Surg, 83: 1174-1185. Meixueiro-Daza-J. Remes-Troche - Case Reports – 2015 doi:10.1046/j.1365-2168.1996.02421.x 6. Luján-Sanchis M, Suárez-Callol P, Monzó-Gallego A, 14. Ota, Masaho, et al. “Incidence of Esophageal Carcinomas et al. Management of primary achalasia: The role of After Surgery for Achalasia: Usefulness of Long-Term and endoscopy. World Journal of Gastrointestinal Endoscopy. Periodic Follow-Up.” American Journal of Case Reports, 2015;7(6):593-605. doi:10.4253/wjge.v7.i6.593. vol. 17, 2016, pp. 845–849., doi:10.12659/ajcr.899800.

POSITION AVAILABLE

Johns Hopkins University School of Medicine, Division of Gastroenterology is looking for a gastroenterology hospitalist with experience in ERCP, EUS, and enteroscopy. Applicants should have at least five years of post fellowship experience in gastroenterology and have completed a two year advanced interventional endoscopy fellowship. Experience in motility and fluency in Spanish helpful.

For further information please contact: Lisa Bach Burdsall, Administrative Supervisor, Division of Gastroenterology and phone: 410-550-7030 email: [email protected]

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