Takahiro Masuda

Data analyses and perspectives on laparoscopic surgery for esophageal achalasia.

In general, the treatment methods for esophageal achalasia are largely classified into four groups, including drug therapy using nitrite or a calcium channel blocker, botulinum toxin injection, endoscopic therapy such as endoscopic balloon dilation, and surgery. Various studies have suggested that the most effective treatment of esophageal achalasia is surgical therapy. The basic concept of this surgical therapy has not changed since Heller proposed esophageal myotomy for the purpose of resolution of lower esophageal obstruction for the first time in 1913, but the most common approach has changed from open-chest surgery to laparoscopic surgery. Currently, the laparoscopic surgery has been the procedure of choice for the treatment of esophageal achalasia. During the process of the transition from open-chest surgery to laparotomy, to thoracoscopic surgery, and to laparoscopic surgery, the necessity of combining antireflux surgery has been recognized. There is some debate as to which type of antireflux surgery should be selected. The Toupet fundoplication may be the most effective in prevention of postoperative antireflux, but many medical institutions have selected the Dor fundoplication which covers the mucosal surface exposed by myotomy. Recently, a new endoscopic approach, peroral endoscopic myotomy (POEM), has received attention. Future studies should examine the long-term outcomes and whether POEM becomes the gold standard for the treatment of esophageal achalasia.

Primary and Redo Antireflux Surgery: Outcomes and Lessons Learned

IntroductionSome patients require one or more reoperative interventions after undergoing primary antireflux surgery (ARS). We compared outcomes after primary and reoperative ARS.MethodsWe queried a prospectively maintained database to identify patients who underwent ARS from September 23, 2003 to May 28, 2016. Patients were categorized into four groups: A (primary ARS), B (first reoperative ARS), C (second reoperative ARS), or D (≥ third reoperative ARS). Patients completed follow-up foregut symptom surveys and satisfaction questionnaires at regular intervals.ResultsIn total, 940 patients were studied (A: nxa0=xa0545, B: nxa0=xa0302, C: nxa0=xa080, D: nxa0=xa013). Age, sex, and BMI were comparable across groups. Heartburn was the most common preoperative symptom in A, whereas dysphagia was more common in B–D. Open approach, mean operative time, and mean blood loss increased from A to D (Pxa0<xa00.05), as did need for Roux-en-Y reconstruction. Vagal injury (2–19–33–54%; Pxa0<xa00.05), visceral perforation (2–20–36–23%; Pxa0<xa00.05), postoperative leak (0.2–2–6–8%; Pxa0<xa00.05 A vs. all), and morbidity (2–10–14–39%; Pxa0<xa00.05) also increased from A to D. At mean follow-up of 36xa0months, the proportion of patients who reported no significant symptoms, excellent satisfaction, and likeliness to recommend this surgery to a friend progressively declined with each successive reintervention (Pxa0<xa00.05).ConclusionsComplications and patient-reported outcomes worsen with each reoperative ARS.

Esophagogastric Junction Morphology and Distal Esophageal Acid Exposure

BackgroundThe Chicago classification has recently added a morphological subclassification for the esophagogastric junction (EGJ). Our aim was to assess the distal esophageal acid exposure in patients with this new Chicago EGJ-type IIIa and IIIb classification.Study DesignFrom a prospectively collected high-resolution manometry (HRM) database, we identified patients who underwent 24-h pH study between October 2011 and June 2015 and were diagnosed with EGJ-type III based on HRM. Chicago EGJ-type III is defined as the inter-peak nadir pressure ≤gastric pressure and a lower esophageal sphincter (LES)–crural diaphragm (CD) separation >2xa0cm [IIIa-pressure inversion point (PIP) remains at CD level and IIIb-PIP remains at LES level]. We classified the patients into reflux group [DeMeester score >14.72 or Fraction time pH (<4)xa0>xa04.2xa0%] and non-reflux group based on 24-h pH study.ResultsFifty patients were identified that satisfied the study criteria, of which 37 patients (74xa0%) were EGJ-type IIIa. In those with EGJ-type IIIb, abdominal LES length (AL) in reflux group was significantly shorter than the non-reflux group (0.8 vs. 1.8, pxa0<xa00.05). EGJ-type IIIa patients showed significantly higher value for DeMeester score and Fraction time pH and more often had a positive pH study than EGJ-type IIIb patients (DeMeester score: 26.7 vs. 11.7, pxa0<xa00.05; Fraction time pH: 7.9 vs. 2.6, pxa0<xa00.05; positive pH study: 81.1 vs. 30.8xa0%, pxa0<xa00.001). Reflux was more common in LES–CDxa0≥xa03xa0cm than that in LES–CDxa0<xa03xa0cm (85 vs. 56.7xa0%, pxa0<xa00.05).ConclusionA subset of patients with >2-cm LES–CD separation (type IIIb) maintain a physiological intra-abdominal location of the EGJ and are less likely to have reflux. A LES–CDxa0≥xa03xa0cm seems to discern a hiatus hernia of clinical significance.

Classification for Esophagogastric Junction (EGJ) Complex Based on Physiology

We propose a new classification for esophagogastric junction (EGJ) incorporating both physiologic and morphologic characteristics. Additionally, we contrast it with the Chicago v 3.0xa0EGJ classification. With Institutional Review Board (IRB) approval, prospectively maintained database was queried to identify patients who underwent high-resolution manometry (HRM) and pH-study between October 2011 and October 2015. Patients with prior foregut intervention, pH study on acid suppression, esophageal dysmotility, or lower esophageal sphincter-crural diaphragm separation of >5 cm were excluded. We classified patients into three groups-Type-A: Complete overlap of lower esophageal sphincter-crural diaphragm (single high-pressure zone); Type-B: Double high-pressure zone with pressure inversion point (PIP) at or above lower esophageal sphincter; Type-C: Double high-pressure zone with PIP below lower esophageal sphincter. A total of 214 included patients were divided into Type-A (n = 101), Type-B (n = 32), and Type-C (n = 81). Abdominal lower esophageal sphincter length (AL), lower esophageal sphincter pressure (LESP), and lower esophageal sphincter pressure integral (LESPI) were significantly lower in Type-C than both Type-A and Type-B [AL(cm): 0.2 vs. 2(P < 0.001) vs. 1.6(P <0.001); LESP(mmHg): 20.1 vs. 32.1(P < 0.001) vs. 29.2(P < 0.001); LESPI(mmHg.cm.s): 187 vs. 412(P < 0.001) vs. 343(P < 0.05)] while overall lower esophageal sphincter length(OL) and Integrated Relaxation Pressure (IRP) were significantly lower in Type-C than Type-A [OL(cm): 2.9 vs. 3.6(P < 0.001); IRP(mmHg): 8.2 vs. 9.6(P < 0.05)]. Type-C patients had significantly higher positive pH score (>14.7) than Type-A and Type-B [72% vs. 47% (P < 0.05) vs. 41% (P < 0.001)]. In Type-C morphology, there is both anatomical and physiological deterioration, weakest lower esophageal sphincter function (abdominal length, lower esophageal sphincter pressure, and lower esophageal sphincter pressure integral) and is most likely to be associated with pathological reflux. This proposed classification incorporates both physiological and morphological derangements in a graded fashion.

Animal Model: Reflux Models in Esophageal Adenocarcinoma

Many mouse models have been developed to mimic the inflammation-metaplasia-dysplasia-carcinoma sequence seen in the gastroesophageal reflux disease (GERD)-Barretts esophagus-esophageal adenocarcinoma progression. Surgical reflux models in mice are technically challenging due to the small size and intolerance to surgical stress of mice. Herein, we detail three representative surgical procedures that allow for creation of an esophageal adenocarcinoma model in mice, either with or without the use of carcinogens. Additionally, we describe a genetic model that shows spontaneous development of esophageal adenocarcinoma.

Swallow-induced esophageal shortening in patients without hiatal hernia is associated with gastroesophageal reflux

Longitudinal esophageal body shortening with swallow-induced peristalsis has been reported in healthy individuals. Esophageal shortening is immediately followed by esophageal re-elongation, and the lower esophageal sphincter (LES) returns to the baseline position. High-resolution manometry (HRM) allows for objective assessment of extent of shortening and duration of shortening. In patients without hiatal hernia at rest, swallow-induced esophageal shortening can lead to transient hiatal hernia (tHH) which at times may persist after the completion of swallow. This manometric finding has not been investigated in the literature, but a question arises whether this swallow-induced transient herniation can effect on the likelihood of gastroesophageal reflux. This study aims to assess the relationship between gastroesophageal reflux and the subtypes of swallow-induced esophageal shortening, i.e. tHH and non-tHH, in patients without hiatal hernia at rest. After Institutional Review Board (IRB) approval, we queried a prospectively maintained database to identify patients who underwent HRM evaluation and 24-hour pH study between January to December 2015. Patients with type-I esophagogastric junction (EGJ) morphology (i.e. no hiatal hernia) according to the Chicago classification v3.0 were included. The patterns of the esophageal shortening with swallows were divided into two subtypes, i.e. tHH and non-tHH. tHH was defined as an EGJ double high-pressure zones (≥1 cm) at the second inspiration after the termination of swallow-induced esophageal body contraction. The number of episodes of tHH was counted per 10 swallows and tHH size was measured for each patient. In total, 41 patients with EGJ morphology Type-I met the inclusion criteria. The mean age was 47.2 years, 35 patients (85.4%) were women, and the mean body mass index was 33.9 kg/m2. The mean number of tHH episodes was 3 out of 10 swallows; mean maximal tHH size was 1.3 cm. Patients who had tHH in ≥3 out of 10 swallows (nxa0=xa016; 39.0%) were more likely to have abnormal DeMeester scores than patients with <3 swallows (56% vs. 28%; Pxa0=xa00.070). Patients with maximal tHH ≥2 cm in at least 1 swallow (nxa0=xa017; 41.5%) were more likely to experience pathological reflux than patients with maximal tHH <2 cm (59% vs. 25%; Pxa0=xa00.029). In conclusion, we showed that, in a subset of patients with Type-I EGJ morphology, swallowing induced transient EGJ double high-pressure zones (≥1 cm) after peristalsis. We have named this new manometric finding the swallow-induced tHH. A high prevalence of pathological reflux disease was observed in patients with maximal tHH ≥2 cm. The degree of swallow-induced tHH could be an early indicator of lower esophageal sphincter dysfunction in patients without manometric hiatal hernia.

Thoracoabdominal pressure gradient and gastroesophageal reflux: insights from lung transplant candidates

Advanced lung disease is associated with gastroesophageal reflux disease (GERD). The thoracoabdominal pressure gradient (TAPG) facilitates gastroesophageal reflux, but the effects of TAPG on gastroesophageal reflux in patients with pulmonary disease have not been well defined. Patients diagnosed with end-stage lung disease are expected to have the most extreme derangement in respiratory mechanics. The aim of this study is to explore the relationship between TAPG and reflux in lung transplant (LTx) candidates. We reviewed LTx recipients who underwent pretransplant esophageal high-resolution manometry and a 24-hour pH study. Patients were excluded if they were undergoing redo LTx, had manometric hiatal hernia, or had previously undergone foregut surgery. TAPG was defined as the intra-abdominal pressure minus the intrathoracic pressure during inspiration. Adjusted TAPG was calculated by the TAPG minus the resting lower esophageal sphincter (LES) pressure (LESP). Twenty-two patients with normal esophageal function tests (i.e., normal esophageal motility with neither manometric hiatal hernia nor pathological reflux on 24-hour pH monitoring) were selected as the pulmonary disease-free control group. In total, 204 patients underwent LTx between January 2015 and December 2016. Of these, 77 patients met inclusion criteria. We compared patients with obstructive lung disease (OLD, nxa0=xa033; 42.9%) and those with restrictive lung disease (RLD, nxa0=xa042; 54.5%). 2/77 patients (2.6%) had pulmonary arterial hypertension. GERD was more common in the RLD group than in the OLD group (24.2% vs. 47.6%, Pxa0=xa00.038). TAPG was similar between the OLD group and the controls (14.2 vs. 15.3 mmHg, Pxa0=xa00.850); however, patients in the RLD group had significantly higher TAPG than the controls (24.4 vs. 15.3 mmHg, Pxa0=xa00.002). Although TAPG was not correlated with GERD, the adjusted TAPG correlated with reflux in all 77 patients with end-stage lung disease (DeMeester score, rsxa0=xa00.256, Pxa0=xa00.024; total reflux time, rsxa0=xa00.259, Pxa0=xa00.023; total number of reflux episodes, rsxa0=xa00.268, Pxa0=xa00.018). Additionally, pathological reflux was seen in 59.1% of lung transplant candidates with adjusted TAPG greater than 0 mmHg (i.e., TAPG exceeding LESP); GERD was seen in 30.9% of patients who had an adjusted TAPGxa0≤xa00 mmHg. In summary, TAPG varies based on the underlying cause of lung disease. Higher adjusted TAPG increases pathological reflux, even if patients have normal antireflux anatomy and physiology (i.e., no hiatal hernia and manometrically normal LES function). Adjusted TAPG may provide further insights into the pathophysiology of GERD.

Do the Data Support Manometric Subclassifications for Ineffective Esophageal Motility

We read the article by Hiestand et al. entitled, “Manometric Subtypes of Ineffective Esophageal Motility” with great interest. The authors have presented subclassification for the manometric diagnosis of ineffective esophageal motility (IEM) which is defined as≥50% ineffective swallows. Authors have subclassified IEM into more severe IEM-Persistens (IEM-P) and less severe IEM-Alternans (IEM-A) depending on presence of no normal swallows (IEM-P) vs. some normal swallows (IEM-A). Authors showed that there is an increased distal esophageal acid exposure, weaker lower esophageal sphincter (LES), and lesser response to proton pump inhibitors (PPI) as measured by the degree of gastric acid suppression in patients with IEM-P. They go on to state that these are due to the more advanced disease state of dysmotility. We are not sure how degree of acid suppression in the stomach can be physiologically related to esophageal motor activity. The pH study was done on PPI in 85% of included subjects. While authors have used separate criteria to define positive study in such patients, the number of such patients should be mentioned and compared for individual subtypes, as inadequate acid suppression can be related to the pH-study results. Further, the authors are implying that the same pathophysiological causes of decreased motility (IEMP4IEM-A) are also leading to a worsening function of LES resting pressure (LESP)—while they themselves show that there is no difference in motility related issues (e.g. impaired bolus transit: 62% in IEM-A and 58% in IEM-P) or prevalence of connective tissue disorders. Mean LESP was significantly lower in IEM-P vs. IEM-A. The authors should discuss and compare the rate of hiatal hernia among 17/36 IEM-P and 129/195 IEM-A patients with available reflux study rather than the overall groups to see its correlation with reflux. Hiatal hernia and/or weak LES are known to be related to reflux, independent of body motility, and can be major confounding factors in the present study. We believe the conclusion that IEM-P is advanced IEM-A is not adequately supported by the data presented. CONFLICT OF INTEREST

The outcomes of 400 laparoscopic Heller-Dor operations (LHD) for esophageal achalasia

METHODS: Mean age was 44.6 (9-83) years, 189 (47%) were women. These patients were divided into 4 groups: very early, early, mid, and late groups. The clinical pathway was introduced from August 2008 (62nd case). Six and 20 patients underwent RPS in both mid and late group, respectively. Their clinical data were collected in a prospectively fashion and retrospectively reviewed. Their characteristics, preoperative clinical conditions, and the therapeutic outcomes of LHD were assessed in terms of gender, age, length of symptoms, morphologic type, the maximum horizontal diameter of the esophagus (Grade I [<3.5 cm], Grade II [ 3.5 cm but <6.0 cm], and Grade III [ 6.0 cm]), operation time, blood loss, perioperative complications, time to start oral intake (TSOI), postoperative hospital stay (POHS), and the incidence of postoperative reflux esophagitis (PORE).