Peroral Endoscopic Myotomy for the Treatment of Achalasia
Peroral Endoscopic Myotomy for the Treatment of Achalasia
POEM was performed without technical difficulties under general anesthesia in 16 patients. The procedure is shown in Figure 1 and Supplementary Video 1 online.
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Figure 1.
Peroral endoscopic myotomy (POEM) procedure. After injection of saline and methylene blue, a 2-cm incision is made into the mucosa (a–c). A submucosal tunnel from the mid-esophagus to the gastric cardia is created using a triangle-tip knife (d–h). The circular muscle fibers are then divided using the triangle-tip knife over a length of 6–15 cm on the esophagus, starting 3 cm below the initial mucosal incision, and the myotomy is extended 2–3 cm onto the gastric cardia (i–k). After complete myotomy, the mucosal entry site is closed using standard endoscopic clips (l).
Four patients were female. The mean age was 45 years (range 26–76), and the mean weight was 85.5 kg (range 64–132) before POEM and 85.0 kg (range 65–136) 3 months after POEM (P=0.555). Eleven patients (69%) had received prior treatment for achalasia with EBD (n=9), botox (n=1), or both (n=1). Among these patients, five had multiple EBDs (up to seven dilatations) and one patient had eight botox treatments before POEM. On baseline, contrast fluoroscopy mean esophageal diameter was 2.8 cm (range 1.4–4.2 cm). No patient with sigmoid type 2 esophagus was included in the study.
Mean procedure time was 114 min (range 65–188) with a mean length of the endoscopic myotomy of 12 cm (range 8–17). There was a learning curve demonstrating a decrease in operating time during the study (Figure 2). In 9/16 cases, full thickness dissection into the peritoneal cavity at the cardia occurred, and in 13/16 cases, full thickness dissection into the mediastinum was observed. Of five patients without previous treatment, four had transmural openings into the mediastinum or peritoneal cavity (80%). Of 11 patients with previous treatment, 8 had transmural openings into the mediastinum or peritoneal cavity (73%). The rate of mediastinal full-thickness openings was unrelated to previous treatment with botox or EBD. In six cases, patients developed minor cutaneous emphysema, and in eight cases, patients developed CO2 pneumoperitoneum, which was relieved with an 18G canula, placed in the lower right abdominal quadrant. In one case, a small mucosal perforation was suspected on endoscopic control at the gastro-esophageal junction, and was clipped.
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Figure 2.
Procedure times for consecutive peroral endoscopic myotomy (POEM) patients.
After POEM, there was a significant increase in CRP (C-reactive protien, P<0.001), a significant increase in leukocyte count (P=0.018; Figures 3 and 4), and a significant decrease in hemoglobin level (P=0.006). Laboratory results showed a CRP of 8 and 15 in two cases, and a CRP ≤ 5 in all other patients before POEM. The mean CRP 24–48 h after POEM was 59, with a range of 12–115. Mean leukocyte count before POEM was 7.3 (range 4.8–11.2). Mean leukocyte count after POEM was 9.2 (range 3.4–16.1). Mean hemoglobin level before POEM was 14.1 (range 10.9–16.4), and 12.9 (range 9.8–15.0) after POEM. No patient developed signs of fever or temperature >38 °C. There was no statistical significant difference for laboratory values between patients in whom POEM was performed without intentional transmural dissection ("partial myotomy", case 1–9) compared with the later group (case 10–16), where an intentional transmural opening at the cardia ("complete myotomy") was performed. However, there was a trend for patients with a complete myotomy for higher postoperative CRP values (P=0.05). Control contrast fluoroscopy before discharge showed a mean esophageal diameter of 1.7 cm (range 1–2.5 cm). Contrast fluoroscopy demonstrated a rapid transit of contrast in 9/16 cases (56%) after POEM. In the group (case 1–9), in which POEM was performed with a partial myotomy, one case (11%) showed a slight delayed esophago-gastric emptying, four cases (44%) showed a delayed esophago-gastric emptying, and four cases (44%) showed rapid esophago-gastric emptying. In the later group (case 10–16), in which a complete myotomy at the cardia was performed, one case (17%) showed a slightly delayed esophago-gastric emptying and all other cases (83%) showed rapid esophago-gastric emptying of the contrast.
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Figure 3.
CRP level before and 24–48 h after peroral endoscopic myotomy (POEM) shown as mean with 95% confidence interval (CI; black) and individual progression for patients with partial myotomy (case 1–9, green lines), and for patients with complete myotomy (case 10–16, blue lines).
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Figure 4.
Leukocyte count before and 24–48 h after peroral endoscopic myotomy (POEM) shown as mean with 95% confidence interval (CI; black) and individual progression for patients with partial myotomy (case 1–9, green lines), and for patients with complete myotomy (case 10–16, blue lines).
Symptom score follow-up was available for all study patients. Treatment success, as defined by a post-myotomy Eckhard score ≤3, was achieved in 94% of cases. Mean Eckhard score pre-treatment was 8.8 compared with a mean post-treatment score of 1.4 (P<0.001; Figure 5). One patient was considered a treatment failure and required additional therapy with EBD. The patient had the same Eckhard score of 9, before and after POEM. This patient underwent two EBD treatments (30 mm and 35 mm; Rigiflex balloon dilator; 17 and 20 psi), resulting in incremental symptom relief with an Eckhard score of 2 after the second EBD. There was no statistical significant difference between patients with a partial (case 1–9) vs. patients with a complete myotomy (case 10–16; P=0.58).
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Figure 5.
Eckhard score before and after peroral endoscopic myotomy (POEM) shown as mean with 95% confidence interval (CI; black) and individual progression for patients with partial myotomy (case 1–9, green lines), and for patients with complete myotomy (case 10–16, blue lines).
Baseline manometry data was available for all study patients. Manometry follow-up was available in 13/16 cases. The mean LES pressure was 27.2 mm Hg pre-treatment and 11.8 mm Hg post treatment (P<0.001; Figure 6 and 7). Three patients refused to undergo follow-up manometry, due to discomfort related to the manometry procedure in all three cases. Among the three patients who did not undergo follow-up manometry, two were satisfied with the POEM result (Eckhard Score ≤3), and the third patient was the treatment failure with an Eckhard score of 9 mentioned above. There was no statistical significant difference between patients with a partial (case 1–9) vs. patients with a complete myotomy (case 10–16; P=0.38).
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Figure 6.
Manometry outcomes (n=16) before and after peroral endoscopic myotomy (POEM) shown as mean with 95% confidence interval (CI; black) and individual progression for patients with partial myotomy (case 1–9, green lines), and for patients with complete myotomy (case 10–16, blue lines). Triangles represent patients with only baseline measurements (n=3).
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Figure 7.
High resolution manometry before (a) and after (b) peroral endoscopic myotomy (POEM) for the patient, case number 2, who suffered from type III achalasia.
In one case, a 1 cm superficial ulcer (Forrest III) at the cardia was detected on routine EGD, 2 days after POEM. The patient was kept in hospital for 7 days and discharged after repeat endoscopy demonstrated healing of the ulcer. One patient—the same patient considered treatment failure based on his post-treatment Eckhard score (see above)—reported retrosternal pain 3 weeks after POEM. EGD demonstrated an ulcer in the distal esophagus (FIII). The ulcer was clipped and the patient was admitted for 3 days for observation and computed tomography scan. Computed tomography scan showed inflammatory thickening of the esophageal wall, with no evidence of leakage or mediastinitis. No other complications, including infections, occurred.
At 3-month follow-up, no patient reported symptoms of gastro-esophageal reflux, but one patient was found to have an erosive lesion (LA classification grade A) at 3-month follow-up EGD. One patient was using PPI medication (p.r.n.) before POEM due to intermittent symptoms of epigastric and retrosternal pain, and was still using it p.r.n. after POEM. The patient reported that neither symptoms nor PPI medication use were altered after POEM. No other patient required or used any medication with PPI/antacids at 3 months. Of note, the patient with an erosive lesion at 3 months reported reflux symptoms at 9 month after POEM and was put on PPI standard dose medication for symptom relief, resulting in an overall reflux complication rate of 6%.
Results
POEM was performed without technical difficulties under general anesthesia in 16 patients. The procedure is shown in Figure 1 and Supplementary Video 1 online.
(Enlarge Image)
Figure 1.
Peroral endoscopic myotomy (POEM) procedure. After injection of saline and methylene blue, a 2-cm incision is made into the mucosa (a–c). A submucosal tunnel from the mid-esophagus to the gastric cardia is created using a triangle-tip knife (d–h). The circular muscle fibers are then divided using the triangle-tip knife over a length of 6–15 cm on the esophagus, starting 3 cm below the initial mucosal incision, and the myotomy is extended 2–3 cm onto the gastric cardia (i–k). After complete myotomy, the mucosal entry site is closed using standard endoscopic clips (l).
Patient Characteristics
Four patients were female. The mean age was 45 years (range 26–76), and the mean weight was 85.5 kg (range 64–132) before POEM and 85.0 kg (range 65–136) 3 months after POEM (P=0.555). Eleven patients (69%) had received prior treatment for achalasia with EBD (n=9), botox (n=1), or both (n=1). Among these patients, five had multiple EBDs (up to seven dilatations) and one patient had eight botox treatments before POEM. On baseline, contrast fluoroscopy mean esophageal diameter was 2.8 cm (range 1.4–4.2 cm). No patient with sigmoid type 2 esophagus was included in the study.
Procedure-related Parameters
Mean procedure time was 114 min (range 65–188) with a mean length of the endoscopic myotomy of 12 cm (range 8–17). There was a learning curve demonstrating a decrease in operating time during the study (Figure 2). In 9/16 cases, full thickness dissection into the peritoneal cavity at the cardia occurred, and in 13/16 cases, full thickness dissection into the mediastinum was observed. Of five patients without previous treatment, four had transmural openings into the mediastinum or peritoneal cavity (80%). Of 11 patients with previous treatment, 8 had transmural openings into the mediastinum or peritoneal cavity (73%). The rate of mediastinal full-thickness openings was unrelated to previous treatment with botox or EBD. In six cases, patients developed minor cutaneous emphysema, and in eight cases, patients developed CO2 pneumoperitoneum, which was relieved with an 18G canula, placed in the lower right abdominal quadrant. In one case, a small mucosal perforation was suspected on endoscopic control at the gastro-esophageal junction, and was clipped.
(Enlarge Image)
Figure 2.
Procedure times for consecutive peroral endoscopic myotomy (POEM) patients.
In-hospital Follow-up
After POEM, there was a significant increase in CRP (C-reactive protien, P<0.001), a significant increase in leukocyte count (P=0.018; Figures 3 and 4), and a significant decrease in hemoglobin level (P=0.006). Laboratory results showed a CRP of 8 and 15 in two cases, and a CRP ≤ 5 in all other patients before POEM. The mean CRP 24–48 h after POEM was 59, with a range of 12–115. Mean leukocyte count before POEM was 7.3 (range 4.8–11.2). Mean leukocyte count after POEM was 9.2 (range 3.4–16.1). Mean hemoglobin level before POEM was 14.1 (range 10.9–16.4), and 12.9 (range 9.8–15.0) after POEM. No patient developed signs of fever or temperature >38 °C. There was no statistical significant difference for laboratory values between patients in whom POEM was performed without intentional transmural dissection ("partial myotomy", case 1–9) compared with the later group (case 10–16), where an intentional transmural opening at the cardia ("complete myotomy") was performed. However, there was a trend for patients with a complete myotomy for higher postoperative CRP values (P=0.05). Control contrast fluoroscopy before discharge showed a mean esophageal diameter of 1.7 cm (range 1–2.5 cm). Contrast fluoroscopy demonstrated a rapid transit of contrast in 9/16 cases (56%) after POEM. In the group (case 1–9), in which POEM was performed with a partial myotomy, one case (11%) showed a slight delayed esophago-gastric emptying, four cases (44%) showed a delayed esophago-gastric emptying, and four cases (44%) showed rapid esophago-gastric emptying. In the later group (case 10–16), in which a complete myotomy at the cardia was performed, one case (17%) showed a slightly delayed esophago-gastric emptying and all other cases (83%) showed rapid esophago-gastric emptying of the contrast.
(Enlarge Image)
Figure 3.
CRP level before and 24–48 h after peroral endoscopic myotomy (POEM) shown as mean with 95% confidence interval (CI; black) and individual progression for patients with partial myotomy (case 1–9, green lines), and for patients with complete myotomy (case 10–16, blue lines).
(Enlarge Image)
Figure 4.
Leukocyte count before and 24–48 h after peroral endoscopic myotomy (POEM) shown as mean with 95% confidence interval (CI; black) and individual progression for patients with partial myotomy (case 1–9, green lines), and for patients with complete myotomy (case 10–16, blue lines).
Three-Month follow-up Symptom Scores
Symptom score follow-up was available for all study patients. Treatment success, as defined by a post-myotomy Eckhard score ≤3, was achieved in 94% of cases. Mean Eckhard score pre-treatment was 8.8 compared with a mean post-treatment score of 1.4 (P<0.001; Figure 5). One patient was considered a treatment failure and required additional therapy with EBD. The patient had the same Eckhard score of 9, before and after POEM. This patient underwent two EBD treatments (30 mm and 35 mm; Rigiflex balloon dilator; 17 and 20 psi), resulting in incremental symptom relief with an Eckhard score of 2 after the second EBD. There was no statistical significant difference between patients with a partial (case 1–9) vs. patients with a complete myotomy (case 10–16; P=0.58).
(Enlarge Image)
Figure 5.
Eckhard score before and after peroral endoscopic myotomy (POEM) shown as mean with 95% confidence interval (CI; black) and individual progression for patients with partial myotomy (case 1–9, green lines), and for patients with complete myotomy (case 10–16, blue lines).
Three-Month follow-up Manometry Outcomes
Baseline manometry data was available for all study patients. Manometry follow-up was available in 13/16 cases. The mean LES pressure was 27.2 mm Hg pre-treatment and 11.8 mm Hg post treatment (P<0.001; Figure 6 and 7). Three patients refused to undergo follow-up manometry, due to discomfort related to the manometry procedure in all three cases. Among the three patients who did not undergo follow-up manometry, two were satisfied with the POEM result (Eckhard Score ≤3), and the third patient was the treatment failure with an Eckhard score of 9 mentioned above. There was no statistical significant difference between patients with a partial (case 1–9) vs. patients with a complete myotomy (case 10–16; P=0.38).
(Enlarge Image)
Figure 6.
Manometry outcomes (n=16) before and after peroral endoscopic myotomy (POEM) shown as mean with 95% confidence interval (CI; black) and individual progression for patients with partial myotomy (case 1–9, green lines), and for patients with complete myotomy (case 10–16, blue lines). Triangles represent patients with only baseline measurements (n=3).
(Enlarge Image)
Figure 7.
High resolution manometry before (a) and after (b) peroral endoscopic myotomy (POEM) for the patient, case number 2, who suffered from type III achalasia.
Immediate and Follow-up Complications
In one case, a 1 cm superficial ulcer (Forrest III) at the cardia was detected on routine EGD, 2 days after POEM. The patient was kept in hospital for 7 days and discharged after repeat endoscopy demonstrated healing of the ulcer. One patient—the same patient considered treatment failure based on his post-treatment Eckhard score (see above)—reported retrosternal pain 3 weeks after POEM. EGD demonstrated an ulcer in the distal esophagus (FIII). The ulcer was clipped and the patient was admitted for 3 days for observation and computed tomography scan. Computed tomography scan showed inflammatory thickening of the esophageal wall, with no evidence of leakage or mediastinitis. No other complications, including infections, occurred.
Reflux Rates on Follow-up
At 3-month follow-up, no patient reported symptoms of gastro-esophageal reflux, but one patient was found to have an erosive lesion (LA classification grade A) at 3-month follow-up EGD. One patient was using PPI medication (p.r.n.) before POEM due to intermittent symptoms of epigastric and retrosternal pain, and was still using it p.r.n. after POEM. The patient reported that neither symptoms nor PPI medication use were altered after POEM. No other patient required or used any medication with PPI/antacids at 3 months. Of note, the patient with an erosive lesion at 3 months reported reflux symptoms at 9 month after POEM and was put on PPI standard dose medication for symptom relief, resulting in an overall reflux complication rate of 6%.