FLIP use in achalasia: comparing POEM and Heller myotomy outcomes: a systematic review and meta-analysis

This systematic review and meta-analysis demonstrate that the intraoperative use of the functional lumen imaging probe (FLIP) significantly enhances the prediction of physiological and clinical outcomes in achalasia patients undergoing laparoscopic Heller myotomy (LHM) or peroral endoscopic myotomy (POEM). Specifically, our results show that the effect of myotomy on FLIP findings does not differ according to surgical approach; whether patients underwent POEM or LHM, FLIP measurements improved consistently. Moreover, we observed a significant increase in the distensibility index (DI), cross-sectional area (CSA), minimum diameter (Dmin), and esophagogastric junction (EGJ) diameter at various distension volumes—findings that mirror previous reports of increased EGJ distensibility following POEM in achalasia [35‐37]. This rise in DI correlates with favorable clinical response, as higher DI values have been noted in patients showing good outcomes compared with those who remain untreated or respond poorly [34]. Unlike the Eckardt score—which relies on subjective symptom reporting—FLIP provides real-time, objective measurements of EGJ function and luminal distensibility, yielding a more comprehensive assessment than high-resolution manometry (HRM) or timed barium esophagography (TBE) [14, 38, 39]. FLIP is also advantageous in patients with low integrated relaxation pressure (IRP), where HRM may be less effective [40]. Notably, FLIP can guide the extent of myotomy during surgery, leading to significant symptomatic relief.14 Supporting this, Holmstrom et al. [16] reported higher clinical success rates (93% vs. 81%, p < 0.05) in patients for whom FLIP was used intraoperatively. Additionally, changes in CSA and DI measured by FLIP have emerged as strong predictors of postoperative outcomes in achalasia [38].

However, in terms of clinical outcomes, our results indicate a significant effect-modifying role of the type of surgery on achalasia patients’ Eckardt score and the rate of reflux esophagitis following myotomy. This effect could be explained by multiple factors. First, POEM is associated with a lower degree of pain compared to LHM [41]. According to our findings, both LHM and POEM reduced the Eckardt score, indicating an improvement in achalasia symptoms. Although both POEM and LHM significantly improved Eckardt scores, our analysis shows that POEM produced a larger reduction, suggesting that it may offer greater symptom relief than LHM. Several studies have demonstrated that intraoperative FLIP not only measures EGJ distensibility but also actively guides the surgical approach. For instance, Holmstrom et al [16] reported extending or deepening the myotomy if the post-cut DI remained below a certain threshold, which led to a higher rate of clinical success (93% vs. 81%, p < 0.05). Likewise, Ilczyszyn et al [18] found that FLIP measurements allowed for shorter laparoscopic myotomies without jeopardizing symptom relief, thus potentially reducing reflux. These findings underscore how DI, CSA, and Dmin can inform real-time decisions, helping surgeons balance adequate LES disruption against the risk of postoperative GERD. Although we noted a greater Eckardt score reduction with POEM overall, most included studies did not report subtype-stratified improvements. Holmstrom et al. [15] observed that type III patients often exhibit lower postoperative DI levels but can still achieve symptom relief. Consequently, it remains unclear whether FLIP usage confers equal benefit across all subtypes or if Type III patients require more extended myotomy.

However, our findings suggest that a higher risk of esophagitis and reflux diseases are disadvantages of POEM. This could be interpreted as a trade-off between symptom relief efficacy and a higher risk of certain complications. The decision between LHM and POEM may then be influenced by a number of factors, including patients’ specific characteristics and preferences, as well as the expertise of the medical team. In terms of other clinical outcomes, our study highlights a favorable clinical success following myotomy in achalasia of 93% with a low complication rate of 10%; however, the rate of post-myotomy GERD was quite high, accounting for 52% of analyzed patients. It should be noted that these findings are only related to post-POEM achalasia patients, given the scarcity of data regarding LHM. In the same context, our findings show that POEM is associated with a reduced risk of presenting with reflux symptoms as compared to the pre-myotomy period.

The timing of FLIP application varies widely, with some studies using it preoperatively [25, 26, 34] and others intraoperatively [9, 12‐19, 22‐24, 27‐33]. Whether FLIP timing influences patient outcomes remains unclear, as prior systematic reviews only examined intraoperative FLIP [14, 42]. To address this, we conducted a subgroup meta-analysis showing that preoperative FLIP was linked to greater increases in DI and CSA at 40 mL, whereas intraoperative FLIP was associated with a lower incidence of reflux esophagitis. Although this timing effect did not extend to clinical success or Eckardt scores, our findings suggest that using FLIP during myotomy may help reduce excessive dissection and subsequent GERD. Interestingly, intraoperative FLIP was tied to higher subjective reflux reports—aligning with GERD studies indicating that reflux symptoms can persist (or remain absent) irrespective of endoscopic findings. Consequently, esophagitis often serves as a more objective marker for GERD, particularly in patients with chronic esophageal symptoms [43].

Intraoperative FLIP use resulted in a greater reduction in post-myotomy IRP than preoperative FLIP application, and similar timing effects were observed in postoperative FLIP measurements (immediate vs. 1 month), suggesting a potential role in creating a durable myotomy—an underexplored concept. Further research is needed to confirm whether these findings persist, as most studies emphasize short-term outcomes. Importantly, assessing EGJ physiology post-myotomy is critical for estimating long-term results and deciding on reintervention [14]. Only one study in our review addressed reintervention rates: Holmstrom et al. [17] reported that 34 of 61 patients required further intervention after POEM. Data on predictive factors remain limited; hence, future studies should clarify reintervention rates for POEM or LHM and identify predictors such as achalasia subtype, Eckardt score, and FLIP metrics. Establishing an ideal intraoperative FLIP threshold to achieve symptom relief without reflux would be optimal, yet current evidence is inconclusive. For instance, Teitelbaum et al. [31‐33] proposed an intraoperative DI range of 4.5–8.5 mm²/mmHg for LHM and POEM, associated with an Eckardt score < 1 and a GERD score < 7,33 while in a 54-patient cohort, a 2.8 mm²/mmHg cutoff for EGJ DI predicted early success (Eckardt < 3) with an AUC of 0.864.44 [44]. Small sample sizes and short follow-ups limit these findings, underscoring the need for larger, standardized studies with extended observation. In our analysis, patients with a good clinical response had higher EGJ DI at 40 mL (FLIP 325 balloon), whereas CSA at 40 mL did not correlate with improvement—perhaps reflecting differing definitions of “good” outcome (e.g., Eckardt < 1 in Familiari et al. [12] vs. < 3 in Ngamruengphong et al. [28]). In terms of intervention failure, only a few studies in our analysis systematically reported reintervention rates. Holmstrom et al. [17] noted that 34 of 61 patients eventually required additional therapy post-POEM, but a subset analysis suggested that low intraoperative DI predicted the need for further interventions. Other investigators have likewise observed that inadequate DI increase during surgery may signal incomplete myotomy and higher failure risk. [16, 18] This highlights the potential for intraoperative FLIP to reduce reinterventions by guiding a more complete initial myotomy. While a few studies measured FLIP both preoperatively and intraoperatively in the same patients, direct comparisons remain limited. Sedation or anesthesia may alter baseline EGJ compliance; therefore, intraoperative FLIP values might differ from awake preoperative measurements. Further research is needed to establish whether these measurements are fully comparable within the same individual.

Our meta-analysis had several limitations. First, all of the available studies in the literature were observational in design, often lacking a comparison group (FLIP vs. no FLIP). Second, none of the analyzed studies made direct comparisons based on the timing of the FLIP application; thus, our results are entirely based on between-study comparisons, which could not account for all clinical and statistical heterogeneity. Importantly, studies reported different FLIP procedure protocols with different definitions for clinical success. This needs to be standardized so that reported findings in the literature can be reproduced. Third, we could not determine the effect modification of various other factors on distensibility among studied patients, such as achalasia subtype, age, gender, or the presence of prior treatment. Fourth, the majority of LHM studies did not report data related to clinical response/outcomes such as esophagitis development, making it difficult to reach conclusions regarding the effect of modification of surgery on patients’ outcomes. Future investigations should consistently incorporate LA grading to permit a more detailed examination of esophagitis severity following myotomy.

Despite these limitations, our meta-analysis had several notable strengths. The cumulative sample size of 1,455 achalasia patients provided robust statistical power and increased generalizability. Although the majority of included studies were retrospective, the inclusion of prospective studies enhances the quality of evidence by mitigating potential biases inherent in retrospective designs. All studies utilized standardized assessment tools—namely, FLIP measurements (DI, CSA, Dmin) and the Eckardt score—ensuring consistent evaluation and facilitating comparative analyses. Diverse geographic representation, including studies from the United States, United Kingdom, South Korea, and Italy, enhances the applicability of the findings across different populations. Evaluating both POEM and LHM procedures allowed for comparisons between surgical techniques regarding FLIP measurements and patient outcomes. Significant improvements in FLIP measurements and reductions in Eckardt scores post-myotomy suggest that FLIP may play a valuable role in assessing myotomy adequacy and predicting patient outcomes.

Our results support the use of FLIP during myotomy to improve outcomes in achalasia patients undergoing POEM or LHM. The meta-analysis highlights the importance of FLIP in predicting treatment outcomes following myotomy. However, the precise FLIP threshold for defining clinical success remains undetermined. While our analysis provides greater confidence compared to previous studies, there is similar statistical heterogeneity. Additionally, the timing of FLIP application can significantly influence post-myotomy FLIP measurements and clinical outcomes. The type of surgery may also modify patients’ post-myotomy outcomes. Therefore, further research stratifying patients by characteristics such as achalasia subtype, age, and prior treatment is necessary.