📄 medicine

Comparative Efficacy of Surgical and Endoscopic Interventions for Primary Achalasia: A Systematic Review and Bayesian Network Meta-Analysis

This Bayesian network meta-analysis of 32 randomized controlled trials reveals that while Heller's Myotomy with Nissen Fundoplication and Pneumatic Dilation combined with Botulinum Toxin are the most effective interventions for treatment success and LES pressure reduction respectively, Anterior POEM also demonstrates high efficacy across both outcomes.

Original authors: Hasnain Wajeeh Saqib, Mujtaba Moazzam, Muhammad Dawood, Abdul Rafay, Ali Raza, Mahad Ahmad, Muhammad Fakher Wali Wani, Muhammad Sahal Zakir, Talha Khan, Abdul Moeez, Daryl R. Ramai, Jorge D. Machicado

Published 2026-06-28

📖 5 min read🧠 Deep dive

CC BY 4.0

Original authors: Hasnain Wajeeh Saqib, Mujtaba Moazzam, Muhammad Dawood, Abdul Rafay, Ali Raza, Mahad Ahmad, Muhammad Fakher Wali Wani, Muhammad Sahal Zakir, Talha Khan, Abdul Moeez, Daryl R. Ramai, Jorge D. Machicado

Original paper licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). ✨ This is an AI-generated explanation of the paper below. It is not written or endorsed by the authors. For technical accuracy, refer to the original paper. Read full disclaimer

Imagine your esophagus (the tube connecting your throat to your stomach) is a busy highway. In a condition called Achalasia, the exit ramp (the Lower Esophageal Sphincter or LES) gets stuck in the "closed" position, and the traffic lights (muscle movements) stop working. Food and liquid pile up, causing pain and difficulty swallowing.

This paper is a massive "race report" that looked at every possible way to fix this stuck exit ramp. The authors didn't just compare two treatments at a time; they used a sophisticated statistical tool (a "Network Meta-Analysis") to put 10 different treatments on a single track and see how they all stack up against each other simultaneously.

Here is the breakdown of their findings using simple analogies:

The Race Track: What They Compared

The researchers gathered data from 32 different studies involving over 1,800 people. They compared:

The Placebo: A "fake" treatment (like a sugar pill) to see what happens if you do nothing active.
The "Temporary Patch": Botulinum Toxin (Botox) injections.
The "Forceful Push": Pneumatic Dilation (blowing up a balloon to stretch the muscle).
The "Surgical Cut": Heller's Myotomy (cutting the muscle with a scalpel, often with a "wrap" to prevent acid reflux).
The "Endoscopic Cut": POEM (cutting the muscle from the inside using a camera, done either from the front or the back).
The "Combo Pack": Balloon stretch + Botox.

The Two Main Goals

The researchers measured two things to decide the winner:

Did the treatment fail? (Did the patient need another procedure or still have symptoms?)
Did the pressure drop? (Did the "exit ramp" actually open up wider?)

The Results: Who Won the Race?

1. The "Did It Work?" Race (Treatment Failure)

Think of this as asking, "Who stayed fixed the longest without breaking?"

The Champions: The Surgical Cut (Heller's Myotomy) and the Endoscopic Cut (POEM) were the clear winners. They were the most reliable at keeping the exit ramp open long-term.
- Analogy: These are like replacing a broken door hinge with a brand new, heavy-duty steel one. It's a permanent fix.
The Runner-Up: The Botox treatment came in last among the active treatments.
- Analogy: Botox is like using duct tape on the door. It might hold for a while, but eventually, it peels off, and the door sticks again. The study confirmed it wears out quickly.
The "Super-Strong" Anomaly: One specific surgery (Heller's + Nissen wrap) looked like it had a perfect score, but the authors warn this is likely a statistical fluke because it was based on only one tiny study where no one failed. They advise taking this specific result with a grain of salt.

2. The "How Wide Did It Open?" Race (Pressure Reduction)

Think of this as asking, "Who made the door open the widest?"

The Surprise Leader: The Combo Pack (Balloon + Botox) ranked highest for opening the door wide.
- The Catch: The authors warn this is tricky. While it opened the door wide on paper (pressure readings), it didn't necessarily keep the patient happy long-term (it ranked 7th for treatment failure).
- Analogy: Imagine you use a sledgehammer and a wedge to force a door open. It opens very wide, but the door might not stay open, or the frame might get damaged. The pressure dropped a lot, but the long-term success wasn't as good as the surgical cuts.
The Consistent Performers: The Surgical Cut and Endoscopic Cut were also very good at opening the door wide, right behind the Combo Pack.
The Underperformer: The Balloon alone (Pneumatic Dilation) actually ranked lowest for how much it reduced pressure, even though it's a common treatment.

The "Trust Score" (Certainty)

The authors gave a "Trust Score" to their findings.

High Trust: They are very confident that doing something active is better than doing nothing (Placebo).
Medium/Low Trust: Because many of these studies were small or didn't have perfect "blind" setups (doctors knew which treatment they were giving), the exact ranking between the top contenders (like Surgery vs. POEM) is a bit fuzzy.
The "Indirect" Problem: Many treatments weren't compared directly against each other in a single study. Instead, the math had to guess the relationship based on how they both performed against a third option. This makes the "Combo Pack" result slightly less certain.

The Bottom Line

If you want a long-term fix: The Surgical Cut (Heller's) or the Endoscopic Cut (POEM) are the best bets. They are the most reliable at stopping the problem from coming back.
If you can't have surgery: Botox or Balloon Dilation are options, but they are more like temporary patches. Botox wears off fast; the balloon is better but still not as permanent as cutting the muscle.
The "Combo" Warning: While combining a balloon and Botox opened the door the widest in this study, the authors say we shouldn't rush to use it as a standard cure yet because the long-term success data is shaky.

In short: The study suggests that for most people, cutting the muscle (either by surgery or camera) is the most reliable way to fix the "stuck door" of Achalasia, while injections and balloons are better suited for temporary relief or for people who can't undergo surgery.

Technical Summary: Comparative Efficacy of Surgical and Endoscopic Interventions for Primary Achalasia

Problem Statement
Primary achalasia is a progressive esophageal motility disorder characterized by lower esophageal sphincter (LES) relaxation failure and absent peristalsis. While multiple therapeutic modalities exist—including pharmacological, endoscopic, and surgical approaches—their comparative efficacy remains uncertain. Current guidelines lack a unified framework to rank these interventions simultaneously. Specifically, the optimal treatment strategy is debated, with existing evidence largely limited to pairwise comparisons that fail to integrate direct and indirect evidence for a comprehensive hierarchy of all available treatments.

Methodology
This study conducted a systematic review and Bayesian network meta-analysis (NMA) adhering to PRISMA-NMA guidelines.

Data Sources: A comprehensive search of PubMed/MEDLINE, Embase, Cochrane CENTRAL, Scopus, and Clinicaltrials.gov was performed from inception through March 4, 2026.
Eligibility: The analysis included 32 randomized controlled trials (RCTs) involving 1,842 adult patients with primary achalasia. Six studies were excluded from the quantitative synthesis due to insufficient data for variance calculation.
Interventions: Ten treatment modalities were evaluated: Placebo, Botulinum Toxin, Pneumatic Dilation (PD), PD + Botulinum Toxin, Anterior POEM, Posterior POEM, Heller's Myotomy (HM), HM + Dor Fundoplication, HM + Toupet Fundoplication, and HM + Nissen Fundoplication.
Outcomes: The primary outcome was treatment failure (clinical non-response or re-intervention). The secondary outcome was the mean change in LES pressure (mmHg).
Statistical Analysis: A Bayesian random-effects NMA was performed as the primary analysis using the gemtc package in R, supplemented by a frequentist NMA (netmeta) as a sensitivity analysis. Markov Chain Monte Carlo (MCMC) sampling was utilized to generate posterior distributions. Model convergence was verified via trace plots and the Gelman-Rubin statistic ($Rhat < 1.05$). Consistency was assessed using node-splitting and the unrelated mean effects (UME) model.
Ranking and Certainty: Treatments were ranked using the Surface Under the Cumulative Ranking Curve (SUCRA) framework. The certainty of evidence was assessed using the CINeMA framework across six domains (within-study bias, reporting bias, indirectness, imprecision, heterogeneity, and incoherence).

Key Results
The analysis included 26 studies contributing to the statistical network. Between-study heterogeneity was low ( $I^2 = 0\%$ ), and no significant inconsistency was detected.

Treatment Failure:
- All active treatments significantly outperformed Placebo.
- Ranking: Heller's Myotomy + Nissen Fundoplication ranked highest (SUCRA 87.7%), followed by Heller's Myotomy alone (79.6%) and Anterior POEM (77.1%).
- Lowest Performance: Botulinum Toxin ranked lowest among active treatments (SUCRA 11.1%).
- Note: The high ranking for HM + Nissen is based on a single study with zero events in one arm and is interpreted with caution.
LES Pressure Reduction:
- All active treatments significantly reduced LES pressure compared to Placebo.
- Ranking: The combination of Pneumatic Dilation + Botulinum Toxin achieved the greatest reduction (SUCRA 93.5%; MD −28 mmHg), followed by Anterior POEM (77.1%) and Heller's Myotomy (62.5%).
- Lowest Performance: Pneumatic Dilation alone ranked lowest (SUCRA 23.3%) among active treatments for this specific outcome.
Consistency and Sensitivity:
- Results were consistent between Bayesian and frequentist analyses.
- Heterogeneity and incoherence were rated as "no concern," while indirectness and imprecision were the primary factors lowering the overall certainty of evidence (mostly rated as Low).

Significance and Claims
The authors claim this study provides the most comprehensive probabilistic synthesis of evidence for primary achalasia to date, extending prior pairwise evidence by quantifying relative efficacy across all modalities simultaneously.

Hierarchy of Efficacy: The study identifies Heller's Myotomy (with or without fundoplication) and Anterior POEM as the most effective interventions for preventing treatment failure, supporting their role as definitive therapies.
Surrogate vs. Clinical Outcomes: A key finding is the discordance between physiological and clinical outcomes. While PD + Botulinum Toxin ranked highest for LES pressure reduction, it ranked seventh for treatment failure. The authors emphasize that LES pressure reduction does not always translate proportionally into sustained symptom relief, cautioning against using manometric outcomes as sole surrogates for clinical efficacy.
Technique Selection: The analysis suggests that the route of myotomy (surgical vs. endoscopic) and the orientation (anterior vs. posterior POEM) are less determinative of failure rates than the principle of LES disruption itself. Consequently, the choice of technique should be guided by operator familiarity and institutional experience rather than probabilistic rankings alone.
Limitations and Caution: The authors explicitly state that the SUCRA rankings are "hypothesis-generating." They highlight limitations including the reliance on indirect evidence for many comparisons (particularly Placebo), the evolution of diagnostic criteria over the study period, and the lack of consistent reporting on achalasia subtypes. The extreme ranking for HM + Nissen is flagged as unreliable due to its basis on a single zero-event study.

In conclusion, the paper posits that while surgical and endoscopic myotomies offer superior long-term success compared to Botulinum Toxin or Pneumatic Dilation monotherapy, the specific ranking of techniques should be interpreted cautiously, with clinical decision-making remaining dependent on patient anatomy and provider expertise.