Extending Myotomy Both Downward and Upward Improves the Final Outcome in Manometric Pattern III Achalasia Patients

Abstract

Background:

Achalasia is currently classified in three manometric patterns. Pattern III is the least common pattern, and reportedly correlated with the worst outcome after all available treatments. We aimed to investigate the final outcome in pattern III achalasia patients after classic laparoscopic myotomy (CLM) as compared with a myotomy lengthened both downward and upward (long laparoscopic myotomy [LLM]).

Materials and Methods:

The study population consisted of 61 consecutive patients with a diagnosis of pattern III achalasia who underwent laparoscopic myotomy between 1997 and 2017. In CLM the total length of the myotomy was ≤9 cm, whereas myotomies extending both downward and upward to a length >9 cm were defined as LLM.

Results:

Of the 61 patients considered, 24 had CLM and 37 had LLM. The postoperative improvement in symptom score differed between the two groups: it dropped from 22 (17–26) to 4 (0–8) in the CLM group and from 20 (17–24) to 3 (0–6) in the LLM group (P < .001). There were 8 of 24 failures (33.3%) in the former group and 4 of 37 (10.8%) in the latter group (P < .05). An abnormal acid exposure was detected after the treatment of CLM in 4 patients and after the treatment of LLM in 3 patients (P = n.s.).

Conclusions:

Although with the intrinsic limitations of this study (retrospective, different time windows of the two procedures, and different lengths of follow-up), the results indicate that extending the myotomy both downward and upward improves the final outcome of laparoscopic Heller-Dor surgery in pattern III achalasia patients. A longer myotomy does not affect any onset of postoperative gastroesophageal reflux.

Background

Esophageal achalasia is a relatively uncommon disease characterized by an impaired smooth muscle activity and unrelaxing lower esophageal sphincter (LES), with an incidence of 1.6 cases per 100,000 cases per year.¹ After the introduction of high-resolution manometry in clinical practice almost 10 years ago, esophageal achalasia was recognized as a heterogeneous disease with three distinct manometric patterns that differ in their response to treatment. According to the online version of the Chicago Classification v3.0 (CC),² the disease is now classified on the basis of three clinically relevant patterns emerging at esophageal manometry: pattern I achalasia is characterized by a minimal contractility in the esophageal body, pattern II by intermittent periods of panesophageal pressurization, and pattern III by spastic distal esophageal contractions.^2–4 Our group recently published a study hypothesizing that these three patterns of achalasia represent three different stages of the same disease, and pointing to evidence of a continuum or evolving pattern (the “Padova theory”).⁵

Pattern III is the least common of the three patterns and it is associated with the worst outcome after all available treatments. Why pattern III achalasia patients have the worst outcome is hard to say. In previously published studies, we noted that, in addition to the spastic area, pattern III achalasia patients also had a longer LES than patients with the other two patterns.⁴ As a result, we have now modified our surgical technique, extending the myotomy both upward into the mediastinum and downward on the gastric side.

In this study, we aimed to compare the final outcome in patients with manometric pattern III achalasia treated with the classic laparoscopic myotomy (CLM) that we have been performing for years as opposed to the recently introduced long laparoscopic myotomy (LLM).

Materials and Methods

We assessed patients diagnosed with pattern III achalasia who underwent laparoscopic Heller-Dor from 1992 to 2017 at the Department of Surgical, Oncological, and Gastroenterological Sciences, University of Padova (Italy). Patients' demographic and clinical data were collected using a dedicated questionnaire. Their scores for dysphagia, food regurgitation, and chest pain were calculated by combining the severity of each symptom (0–6) with its frequency (0 = never, 1 = occasionally, 2 = once a month, 3 = every week, 4 = twice a week, 5 = daily) to obtain an overall symptom score.⁶

Before surgery, all patients had barium swallow X-rays to assess the diameter and shape of the esophagus, and conventional or high-resolution esophageal manometry and endoscopy to rule out cardia malignancies. The postoperative follow-up included examining patients 1, 6, and 12 months after their operation, and every 2 years thereafter, using the same questionnaire as before their treatment. Barium swallow was required 1 month after surgery and in the event of recurrent dysphagia or food regurgitation. Esophageal manometry, using the same technique as before surgery, was performed 6 months after surgery, together with 24-hour pH monitoring to check for any abnormal acid exposure of the distal esophagus. Endoscopy was recommended 12 months after surgery, and then every 2 years thereafter, to identify and control any complications of gastroesophageal reflux disease. Treatment failure was defined when a patient needed an additional procedure for persistent and/or recurrent symptoms.

This was an observational study, and all procedures were performed routinely for the diagnosis and follow-up of patients with esophageal achalasia undergoing laparoscopic Heller-Dor, so no institutional review board approval was required. The study was approved by the Research Committee of our Department of Surgical, Oncological, and Gastroenterological Sciences (University of Padova).

Manometric pattern

All patients underwent conventional or high-resolution manometry. A pneumohydraulic perfusion system was used for conventional manometry (Menfis, Bologna, Italy) and the procedure has been described in detail elsewere.⁴ On conventional manometry, pattern III was identified according to the original classification proposed by our group, that is, when at least two spastic waves were detected (lasting >6.0 seconds with an amplitude >70 mmHg).⁴ (Fig. 1) On high-resolution manometry, pattern III was identified following the CC v3.0 criteria: high median integrated relaxation pressure (IRP; >15 mmHg†), no normal peristalsis, premature (spastic) contractions with distal contractile integral >450 mmHg·s·cm with ≥20% of swallows³ (Fig. 2).

FIG. 1.

Conventional manometry trace of pattern III achalasia.

FIG. 2.

High-resolution manometry trace of pattern III achalasia.

Laparoscopic Heller-Dor procedure

The main steps in the surgical technique for laparoscopic Heller-Dor have been described in detail elsewhere.⁷ After identifying the esophagogastric junction, the myotomy was extended 6–7 cm toward the mediastinal esophagus, and 2 cm downward on the gastric side.

We defined myotomies with a total length of ≤9 cm as CLM, and myotomies elongated both downward and upward to a total length >9 cm as LLM. All pattern III patients treated before 2010 had CLM, whereas patients seen after 2010 had LLM. All procedures were recorded. Two surgeons and authors (M.C. and R.S.) further certify the length of the myotomy and reviewed all the videos of the procedures for the purposes of this study.

Statistical analysis

Continuous data are expressed as medians and interquartile ranges (IQRs). Categorical data were compared between the two groups (CLM and LLM) using Fisher's test, and continuous data using the Mann–Whitney nonparametric test. Pre- to postoperative variations in symptom scores, resting LES pressure, and IRP were compared between the two groups using Wilcoxon's nonparametric test. A P value of < .05 was considered significant.

Results

The median age of the 61 patients forming the study sample (M:F = 39:22) was 52 years (IQR:38–62). Four patients had previously undergone endoscopic treatment with pneumatic dilations.

The median preoperative esophageal diameter was 30 mm (25–35) and none of the patients had a sigmoid-shaped mega-esophagus at the time of their achalasia diagnosis. The median symptom duration was 12 months (8–24), and the median symptom score was 21 (16–22). The patients presenting with chest pain amounted to 44 (72%), with a median chest pain score of 7 (3–8).

All procedures were completed laparoscopically, and the mortality and postoperative complication rates were nil.

CLM versus LLM

During the study period, 24 patients had CLM and 37 patients had LLM.

The symptom scores, duration of symptoms, manometric findings (LES resting pressure and IRP), and esophageal diameters were similar in the two groups. The only difference between the two groups concerned gender and age of the patients at the time of their diagnosis: in the LLM group, there were more males and patients were also older than in the CLM group (Table 1). One patient in the CLM group and 3 patients in the LLM group had previously undergone one or two sessions of pneumatic dilation (P = n.s.).

Table 1.

Preoperative Demographic and Clinical Data

	CLM	LLM	P
Gender (M/F)	11/13	28/9	.028
Age	46 (30–53)	57 (41–67)	.026
Duration of symptoms	12 (6–19)	13 (5–27)	.45
Previous treatment	1/24	3/37	.9
Preoperative symptom score	22 (17–26)	20 (17–24)	.64
Preoperative chest pain score	8 (6–10)	7.5 (4–8)	.28
No. of patients with chest pain	15	29	.25
LES resting pressure	34.5 (23.2–51.2)	44.9 (30–50.3)	.32
IRP	22.3 (14.7–33.3)	19.9 (17–43.6)	.81
Esophageal diameter	30 (25–36)	25 (25–30)	.22

CLM, classic laparoscopic myotomy; LLM, longer laparoscopic myotomy; LES, lower esophageal sphincter; IRP, integrated relaxation pressure.

All procedures were completed laparoscopically. One mucosal perforation was detected and repaired intraoperatively in the LLM group. The median length of the myotomy was 8 cm (IQR:8–9) in the CLM group and 10 cm (IQR:10–12) in the LLM group (P < .001). The median follow-up was 94 months (IQR:52–126) in the CLM group and 24 months (IQR:16–40) in the LLM group.

The two groups experienced a different mean improvement in their symptom scores after the myotomy, which dropped from 22 (17–26) to 4 (0–8) in the CLM group and from 20 (17–24) to 3 (0–6) in the LLM group (P < .001). The treatment failed in 8 of 24 (33.3%) patients in the CLM group and in 4 of 37 (10.8%) in the LLM group (P < .05). (Table 2) All patients whose surgery failed subsequently underwent one or more endoscopic pneumatic dilation treatments, obtaining an improvement in their symptom scores. After the myotomy, an abnormal acid exposure was identified in 4 patients in the CLM group and in 3 patients in the LLM group (P = n.s.).

Table 2.

Intra- and Postoperative Data

	CLM	LLM	P
Mucosal perforation	0	1	n.s.
Length of myotomy	8 (8–9)	10 (10–12)	<.01
Follow-up (months)	94 (52–126)	24 (16–40)	<.001
Postoperative symptom score	4 (0–8)	3 (0–6)	n.s.
Postoperative chest pain score	0 (0–5)	0 (0–0)	n.s.
Failures	8/24 (33.3%)	4/37 (10.8%)	.047
Postoperative pathological acid reflux by pH study	4	3	n.s.

CLM, classic laparoscopic myotomy; LLM, longer laparoscopic myotomy.

Discussion

Before the introduction of high-resolution manometry, esophageal achalasia was considered a single disease, even though Vantrappen described a “spastic” manometric subtype as “vigorous achalasia.”⁸ Ten years ago, the Northwestern University (Chicago) Esophageal group² were the first to describe three different manometric patterns of achalasia, and they defined the spastic subtype as “pattern III.” Their first analysis on the clinical relevance of these different subtypes indicated that pattern III had the worst outcome.² This was confirmed by several studies, including one from our own group showing that pattern III patients had recurrent symptoms after laparoscopic Heller-Dor in 30.4% of cases—as opposed to 14.6% and 4.7% in pattern I and pattern II patients, respectively.⁴

In the data set from the European randomized trial comparing pneumatic dilation with laparoscopic Heller-Dor, the proportion of patients with pattern III achalasia with a positive final outcome after dilatation was 40% as opposed to 86% of those treated with myotomy (although the difference was not statistically significant due to the small number of patients with pattern III).⁹

These findings were confirmed by Pratap et al. too, who showed that response to pneumatic dilation was better in pattern II (90%) than in pattern I (63%) or pattern III (33%); the authors concluded that pattern III was a strong predictor of a negative final outcome after pneumatic dilation.¹⁰

For the time being, the role of peroral endoscopic myotomy (POEM) in patients with pattern III achalasia is still unclear because only a handful of published studies have assessed this issue. Naby reported that the positive final outcome rates at 3-year follow-up dropped from pattern II (93.5%) to pattern I (87.5) to pattern III (75%). Here again, their data were not statistically significant because of the small number of patients with pattern III achalasia enrolled in the study.¹¹ In contrast, Kim et al. found that, at a median follow-up of 16 months, POEM achieved a good clinical outcome for all manometric subtypes (98%, 100%, and 91% for patterns I, II, and III, respectively).¹²

In previously published studies, we noted that pattern III achalasia patients had a longer LES than patients with pattern I or II, as well as the characteristic spastic area of the distal esophagus.^4,13 This prompted us to modify our surgical technique for patients with pattern III achalasia: since 2015, we have extended the myotomy both upward into the mediastinum and downward on the gastric side. None of our patients had a sigmoid-shaped mega-esophagus (radiological grade IV), so surgically extending the myotomy to the mediastinum did not pose any technical problems. After introducing this modification, we found that performing a longer myotomy coincided with a drop in the incidence of failures from 33% to ∼10%. It is difficult to say whether this improvement was due to the extension of the myotomy upward to the spastic area or downward on the gastric side. Further studies will be needed to clarify this aspect.

Our although preliminary data compare well with those of a recent study by Crespin et al.,¹⁴ who found the outcome in pattern III patients comparable with the results obtained in the other subgroups of achalasia patients when the myotomy was extended into the gastric wall. Using a longer myotomy, the POEM technique would seem to be the best treatment for spastic pattern III achalasia, but its rarity means that published data are still scarce. One recent report on 32 pattern III patients undergoing POEM described a good outcome in 90% of cases at 2-year follow-up.¹⁵ Judging from these studies and our own data, we can only say that laparoscopic Heller-Dor and, probably, POEM should be the first treatment offered to patients with pattern III achalasia, whereas pneumatic dilation (given its modest effect) should be considered only for patients with a high anesthesiological risk.

Another obscure aspect of the manometric pattern III in achalasia concerns its position in the latest classification of motility disorders and achalasia because some authors have suggested that pattern III might be a different disease from the other two subtypes of achalasia.^16–18 In two recent publications, we advanced our “Padova theory”: we found evidence to indicate that the three different manometric patterns of achalasia represent different stages in the evolution of the same disease, where pattern III would be the earlier stage, pattern II an intermediate stage, and pattern I the end stage. The main findings supporting this theory concern preoperative esophageal diameter and the occasional progression of pattern III patients to pattern II without any treatment.^5,13 In addition, Jalil et al. recently reported on the case of a patient assessed with impedance manometry who had all three contraction patterns of achalasia (50% of the contractions were simultaneous and spastic): the impedance method revealed some stasis above the esophagogastric junction, and barium swallow showed the typical “bird's beak” sign.¹⁹

The data obtained in this study showed that all pattern III patients who underwent laparoscopic Heller-Dor had a clinical history and symptoms typical of achalasia, and a barium swallow showing grade I–II disease. That said, the “Padova theory” cannot explain why pattern III achalasia patients reportedly have a worse outcome with all available therapies.^{2,4,10–13,20}

Our present study shows that the outcome of pattern III patients who undergo Heller myotomy is actually similar to the reported outcome in patients with the other two patterns of achalasia. On univariate and multivariate analyses, moreover, the surgical procedure (i.e., a longer myotomy) was the only factor to predict a positive result. A longer myotomy did not influence postoperative acid exposure, as assessed by 24-hour pH monitoring. These results confirmed our previous findings and those reported by Pellegrini.^6,21

This study had some intrinsic limitations: it was retrospective, and there is a different time window for the two procedures being compared, and a consequently different follow-up. In a recent publication on 1001 myotomies performed by our group, however, we found that the median time to recurrence was 12 months, with only a few patients' symptoms recurring after 2 years. In this study, both groups had a follow-up of >12 months, so we are confident that these results will be confirmed in the future, with a longer follow-up.²²

Despite these limitations, we feel that our results entitle us to claim that extending the length of the myotomy both downward and upward improves the final outcome of the laparoscopic Heller-Dor procedure in patients with pattern III achalasia. A longer myotomy also has no influence on any onset of postoperative gastroesophageal reflux.

Authors' Contributions

Study design was performed by R.S., M.C., M.V., D.B., L.M., and L.P. Data acquisition was carried out by R.S., M.C., L.N., and L.P. Data interpretation was done by R.S., M.C., M.V., D.B., and L.M. Drafting of the article was carried out by R.S., L.P., M.C., D.B., M.V., G.C., L.N., L.M., and S.M. Final approval of the article was done by R.S., L.P., M.C., D.B., G.C., L.N., M.V., L.M., and S.M. The following authors agreed to be accountable for all aspects of this study: R.S., L.P., M.C., D.B., G.C., M.V., L.N., L.M., and S.M.

Footnotes

Disclosure Statement

No competing financial interests exist.

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