Age-related impairment of esophagogastric junction relaxation and bolus flow time

AIM To investigate the functional effects of abnormal esophagogastric(EGJ) measurements in asymptomatic healthy volunteers over eighty years of age. METHODS Data from 30 young controls(11 M, mean age 37 ± 11 years) and 15 aged subjects(9 M, 85 ± 4 years) were compared for novel metrics of EGJ-function: EGJcontractile integral(EGJ-CI), total EGJ-CI and bolus flow time(BFT). Data were acquired using a 3.2 mm, 25 pressure(1 cm spacing) and 12 impedance segment(2 cm) solid-state catheter(Unisensor and MMS SolarGI system) across the EGJ. Five swallows each of 5 m L liquid(L) and viscous(V) bolus were analyzed. Mean values were compared using Student's t test for normally distributed data or Mann Whitney U-test when non-normally distributed. A P value 0.05 was considered significant.RESULTS EGJ-CI at rest was similar for older subjects compared to controls. Total EGJ-CI, measured during liquid swallowing, was increased in older individuals when compared to young controls(O 39 ± 7 mm Hg.cm vs C 18 ± 3 mm Hg.cm; P = 0.006). For both liquid and viscous bolus consistencies, IRP4 was increased(L: 11.9 ± 2.3 mm Hg vs 5.9 ± 1.0 mm Hg, P = 0.019 and V: 14.3 ± 2.4 mm Hg vs 7.3 ± 0.8 mm Hg; P = 0.02) and BFT was reduced(L: 1.7 ± 0.3 s vs 3.8 ± 0.2 s and V: 1.9 ± 0.3 s vs 3.8 ± 0.2 s; P 0.001 for both) in older subjects, when compared to young. A matrix of bolus flow and presence above the EGJ indicated reductions in bolus flow at the EGJ occurred due to both impaired bolus transport through the esophageal body(i.e., the bolus never reached the EGJ) and increased flow resistance at the EGJ(i.e., the bolus retained just above the EGJ).CONCLUSION Bolus flow through the EGJ is reduced in asymptomatic older individuals. Both ineffective esophageal bolus transport and increased EGJ resistance contribute to impaired bolus flow.     

Solid bolus transit by esophageal scintigraphy in patients with dysphagia and normal manometry and radiography

Scintigraphic technique was used to study esophageal transport of a solid bolus in 16 patients with dysphagia but with normal manometry, and negative acid perfusion tests, acid clearing tests, and pH reflux tests. Radiology performed on 14 of the 16 patients showed no evidence of organic lesions. Half the patients had abnormal findings at scintigraphy, with either bolus retention in the upper part of the esophagus or prolonged transit time as compared to a group of 20 asymptomatic subjects. Scintigraphy can be regarded as a valuable complement in the objective documentation of dysphagia when other diagnostic methods fail.The study was supported by a grant from the Swedish Medical Research Council, project No. 17X-4860.     

Adenocarcinoma of the esophagogastric junction

Adenocarcinoma of the esophagogastric junction (EGJ) has increased rapidly in incidence in the latter half of the twentieth century. The increase in incidence has affected white men between the ages of 40 and 60 disproportionately. Understanding the etiology and improving treatment requires careful classification of EGJ tumors. A recent consensus conference recognized three types of EGJ adenocarcinomas: distal esophageal, cardia, and subcardia gastric. Distal esophageal adenocarcinomas are associated with Barrett's esophagus. Helicobacter pylori infection may play a role in some adenocarcinomas of the subcardia, but the association is unproven. Therapy for all types of EGJ tumors is surgical, but multimodal forms of treatment are commonly used because of the advanced stage at which these tumors often present. Several endoscopic options exist for primary therapy of early-stage tumors and for palliation.     

Comparison of bolus transit patterns identified by esophageal impedance to barium esophagram in patients with dysphagia

Bolus transit through the esophagus has not been validated by videoesophagram in patients with dysphagia and changes in impedance with abnormal barium transit have not been described in those patients. The aim of this study was to compare esophageal impedance findings with barium esophagram measurements in patients with dysphagia. The consecutive patients with dysphagia underwent conventional multichannel esophageal impedance manometry, after which a barium videoesophagram was performed simultaneously with multichannel esophageal impedance manometry using a mean of three swallows of barium. Esophageal emptying patterns shown in the esophagogram were classified by the degree of intraesophageal stasis and presence of intraesophageal reflux. Bolus transit patterns in impedance were classified as complete and incomplete transit. Sixteen patients (M : F = 8 : 8, mean age, 47 years) were enrolled. Their manometric diagnosis were normal (n= 6), ineffective esophageal motility (n= 1), diffuse esophageal spasm (DES; n= 2), and achalasia (n= 7). Sixty‐three swallows were analyzed. According to impedance analysis, 21/22 swallows with normal barium emptying showed complete transit (96%) and 31/32 swallows with severe stasis showed incomplete transit (97%). Nine swallows with mild stasis showed either complete or incomplete transit patterns in impedance. Swallows with mild barium stasis and complete transit in impedance were observed in patients who had received treatment (two patients with achalasia with history of esophageal balloonplasty and a patient with DES after nifedipine administration). Impedance reflected severe stasis with retrograde barium movement and described typical bolus transit patterns in patients with achalasia and DES. In conclusion, impedance‐barium esophagram concordance is high for swallows with normal esophageal emptying and for severe barium stasis in patients with dysphagia.     

Adenocarcinoma of the esophagogastric junction in Japan

BACKGROUND/AIMS: The prognosis of adenocarcinoma of the esophagogastric junction is worse than that in adenocarcinoma of other parts of the stomach. In particular, the clinical features and prognosis of adenocarcinoma of the esophagogastric junction and the differences between Siewert's type II and III tumors in Japan were evaluated. METHODOLOGY: We analyzed one hundred and forty patients with adenocarcinoma of the esophagogastric junction including one patient with a type I tumor, sixty-seven patients with type II tumors, and seventy-two patients with type III tumors. RESULTS: The prognosis of patients with type III tumors was poorer in comparison to that of type II tumors in adenocarcinoma of the esophagogastric junction (p<0.05). A significant difference was observed in the survival of patients with type III tumors between those with positive and negative lymph nodes (p<0.001). However, there was no such difference in patients with type II tumors. In a multivariate analysis, lymph node metastasis, age and the depth of tumor invasion were all found to be independent prognostic factors. CONCLUSIONS: The prognosis of patients with lymph node metastasis of type III adenocarcinoma of the esophagogastric junction was found to be extremely poor. An aggressive treatment after surgery may therefore be necessary to improve the survival of this population.     

Histopathological features of the esophagogastric junction

The esophagogastric junction has diverse histological features including cardiac mucosa, pancreatic acinar metaplasia, and squamous metaplasia-like change. Esophageal cardiac glands are scattered in the lamina propria, predominating in the distal esophagus. It was suggested that cardiac and oxyntocardiac mucosa were not normally present and, when present, represented pathological metaplastic epithelia resulting from reflux damage of squamous epithelium. This hypothesis has created a great deal of controversy, which has not yet been resolved. Moreover, the extent of the cardiac mucosa itself has recently become a focus of interest. Our results showed the high incidence of cardiac mucosa. The pathogenesis of pancreatic acinar cells has been the subject of considerable speculation. Pancreatic acinar cells have been reported in the gastric mucosa of pediatric subjects, suggesting a congenital origin, whereas in other reports the presence of pancreatic heterotopia has almost invariably been associated with inflammation and atrophy. Squamous metaplasia-like change, also known as multilayered epithelium, which resembles the cervical transformation zone, is composed of multiple layers of basally located flattened squamoid cells covered by columnar mucous cells. In some reports, it was concluded that multilayered epithelium as a precursor of Barrett's mucosa. However, there was an opinion that squamous metaplasia-like change or multilayered epithelium was only a metaplasia that was sometimes seen at the esophagogastric junction (EGJ).     

Interrogation of esophagogastric junction barrier function using the esophagogastric junction contractile integral: an observational cohort study

The esophagogastric junction contractile integral (EGJ‐CI), designed similar to distal contractile integral (DCI), has been proposed as a metric to evaluate EGJ barrier function. We determined normative values and evaluated EGJ‐CI in predicting esophageal acid exposure time (AET) and symptomatic outcome in this observational cohort study. High‐resolution manometry (HRM) studies were reviewed in 188 patients (55.2 ± 0.9 years, 64% female) undergoing ambulatory pH monitoring off therapy. Dominant symptoms and global symptom severity (GSS) were determined on questionnaires initially and upon follow‐up. EGJ‐CI was measured using the DCI tool placed across the EGJ and compared to normal controls (n = 21, 27.6 ± 0.6 years, 52% female). EGJ‐CI was calculated both for a single respiratory cycle (SRC, in mmHg.cm.s) and corrected for respiratory cycle (CRC, mmHg.cm). Univariate and multivariate analyses determined the predictive potential of EGJ‐CI in terms of AET and post‐therapy GSS at follow‐up, controlling for medical versus surgical therapy. Mean EGJ‐CI values were significantly lower when AET was abnormal; EGJ‐CI/SRC and EGJ‐CI/CRC were 86% concordant (r = 0.84). Using receiver operating characteristic analysis, values below 121.8 mmHg.cm.s (EGJ‐CI/SRC) and 39.3 mmHg.cm (EGJ‐CI/CRC) predicted abnormal AET best (sensitivity 0.61 and 0.65, specificity 0.61 and 0.57, respectively). On univariate and multivariate analysis, the EGJ‐CI discriminated normal from abnormal AET better than conventional LES parameters (P ≤ 0.02). After 2.7 ± 0.1 years follow‐up, EGJ‐CI below identified thresholds predicted better symptom response to antireflux surgery compared to medical therapy (P = 0.009). EGJ‐CI is a novel HRM metric that has potential to complement or replace currently used basal LES and EGJ parameters.     

Biomechanics of the esophagogastric junction in gastroesophageal reflux disease

Gastroesophageal reflux is inherently mechanical in nature, driven by the pressure difference between the stomach and the esophagus in the setting of a relaxed or hypotensive sphincter. Recent advances in our understanding of esophagogastric junction (EGJ) biomechanics in the etiology of gastroesophageal reflux disease are highlighted here. We focus this review on three critical areas: the anatomy and physiology of the EGJ that predispose the junction to reflux, the mechanical compliance of the EGJ musculature that has significant pathophysiologic underpinnings, and the trans-sphincteric pressure gradients during gastro-esophageal reflux. We also examine the mechanistic basis of a higher incidence of reflux in obese patients and conclude with some observations on the future of understanding EGJ biomechanics.     

Revised criterion for diagnosis of ineffective esophageal motility is associated with more frequent dysphagia and greater bolus transit abnormalities

BACKGROUND: Ineffective esophageal motility (IEM) has been defined by the presence of > or = 30% liquid swallows with contraction amplitude < 30 mmHg (ineffective swallows) in the distal esophagus ("old" IEM). A recent study with combined multichannel intraluminal impedance and manometry (MII-EM) raised the question whether the manometric diagnosis of IEM should be based on a new definition: > or = 50% ineffective liquid swallows ("new" IEM). The aim of this study was to evaluate the association between the number of ineffective liquid swallows and symptoms and bolus transit in patients with "new" or "old" IEM who underwent MII-EM studies using 10 liquid and 10 viscous swallows. MATERIALS AND METHODS: There were 150 patients with "old" IEM included in the study. The patients diagnosed with "old" IEM (N = 150) (group A) were compared with those who retained a manometric diagnosis of IEM by the new definition (N = 101) (group B). The patients who did not retain their manometric diagnosis of IEM by the new definition (N = 49) (group C) were compared with group B. IEM was characterized as mild (normal bolus transit for both liquid and viscous swallows), moderate (abnormal bolus transit either for liquid or viscous swallows), or severe (abnormal bolus transit for both liquid and viscous swallows). RESULTS: There was no statistical difference in frequency of mild, moderate, or severe IEM and frequency of symptoms between group A and B. Group C had a significantly higher frequency of mild IEM and significantly lower frequency of severe IEM than group B. Heartburn (25.7%vs 10.2%, P= 0.03) and dysphagia (24.8%vs 12.3%, P= 0.08) showed a trend towards a greater frequency in group B than in group C. CONCLUSION: Our study indicates that IEM with > or = 50% ineffective liquid swallows is frequently associated with bolus transit abnormalities and esophageal symptoms. Our results underscore the rationale for using the new definition of IEM.     

Adenocarcinoma of the esophagogastric junction: a summary of responses to a questionnaire on adenocarcinoma of the esophagus and the esophagogastric junction in Japan

Adenocarcinoma of the esophagogastric junction is recognized as a distinct clinical entity; however, the choice of surgical approaches is controversial. To analyze the results of surgery among patients with adenocarcinoma of the esophagus (type I) and the cardia (type II) based on Siewert's classification in Japan, surgical procedures, histopathologic characteristics, and outcome were re-evaluated according to the TNM classification in 1263 patients with adenocarcinoma of the esophagus (type I) and the cardia (type II) through a questionnaire sent to the members of the Japanese Society of Esophageal Diseases. One hundred and thirty-four (10.6%) patients had type I tumors and 1129 (89.4%) patients had type II tumors. There were significant differences in sex distribution and associated intestinal metaplasia in the esophagus between patients with type I and type II tumors. Although different surgical approaches were performed, the overall 5-year survival rate was 53% without any difference between the two groups. The significant prognostic factors in general linear models were R category, pN category, and differentiation, but not pT category. There was no difference in survival between patients with stage IIB and III disease. The survival rate of the patients who underwent a transhiatal approach was similar to that of those undergoing a transthoracic approach. The results suggest that Siewert's classification (type I and type II) is useful in planning treatment strategy for adenocarcinoma of the esophagogastric junction. Lymph node metastasis was the most important prognostic factor, and staging based on the number of lymph node metastases or the extent of lymph node metastasis is necessary.     

Left thoracoabdominal approach for adenocarcinoma of the esophagogastric junction

BACKGROUND/AIMS: To evaluate usefulness of esophagogastrectomy via left thoracoabdominal (LT) approach for adenocarcinoma of the esophagogastric junction (AEG), the results of surgery stratified by Siewert's classification, were analyzed retrospectively. METHODOLOGY: The tumor diameter, distance of the proximal tumor border from the esophagogastric junction, and length of the esophagus in the resected specimens of consecutive 171 AEG patients were measured. The surgical approach was classified as total esophagectomy (TE), esophagogastrectomy via LT, or transhiatal/abdominal (HA) approach. RESULTS: Sixteen patients underwent TE, 71 had LT, and 84 had HA. Overall survival of the TE and LT groups was significantly lower than that of the HA group. The difference was seen between LT and HA for type II T3 tumors, but the tumor diameter in LT was significantly larger than that in HA. The approach could not be determined by Siewert's classification, but by distance of proximal tumor border from the junction. The tumors with distance over 5cm might be indicated for the TE approach; 5-3cm, the LT; within 3cm, the HA. The percentage of patients in whom the LT approach is indicated might be only 19%. CONCLUSION: Left thoracoabdominal esophagogastrectomy may be valid for some AEG.     

Primary composite tumor with bipartite differentiation of the esophagogastric junction

We describe a rare case of primary composite tumor with bipartite differentiation of the esophagogastric junction. An 88‐year‐old Japanese man with a history of distal subtotal gastrectomy was admitted to Harima Hospital of Ishikawajima‐harima Heavy Industries with dysphagia of 2 months duration. Endoscopy showed a round, sharply demarcated lesion with a smooth surface in the lower esophagus. Distally, the lesion was irregular and elevated with a deep central depression. The gastric cardia was slightly elevated with a granular mucosa. After surgical resection, histological and histochemical findings showed a primary composite tumor with bipartite differentiation of the esophagogastric junction. There is no evidence of recurrence for 21 months after surgery without adjuvant chemotherapy. The present case indicates the necessity for a careful evaluation for accessory lesions in composite tumors containing small cell carcinoma of the esophagogastric junction, and that resectional surgery might not only be the treatment of choice, but also important in the evaluation of immature composite tumor without distant metastases.     

Esophageal intramural spreading from an adenocarcinoma of the esophagogastric junction

Although intramural spreading from gastric carcinoma to the esophageal wall is occasionally reported, longitudinal intramural lesion of the esophagus is very rare. We herein report the case of a patient found to have a carcinoma of the gastric cardia with intramural spreading to the esophagus approximately 7.0 cm in length. A 65-year-old man was admitted to our department suffering from a persistent midthoracic pain and mild dysphagia during the previous 3 months. Upper gastrointestinal studies revealed an oval submucosal tumor of the lower esophagus and a flare irregular lesion on the esophagogastric junction. An endoscopic ultrasonography showed the main tumor was in the submucosal layer and invaded beyond the muscularis propria. Histopathological examination of the resected specimen confirmed a poorly differentiated adenocarcinoma, 7.0 cm in length, which penetrated through the gastric wall, and invaded the submucosal layer of the esophagus. When only a few scattered carcinoma cells infiltrate only the mucosa or submucosa, it is difficult to diagnose the extent of esophageal invasion. In treating patients with gastric cancer with esophageal invasion, it is important to determine the safety of the proximal margin for esophageal resection. Histological examination using frozen sections obtained during surgery is essential for deciding the operative safety margin.     

Kinematic pharyngeal transit times in myopathy: Evaluation for dysphagia

Measurement of kinematic pharyngeal transit times, a new videofluoroscopy technique, provides useful quantitative data to supplement the qualitative data previously available from videofluoroscopy swallowing studies. Kinematic pharyngeal transit times have not previously been reported for subjects with myopathy. This study demonstrates the use of quantitative kinematic pharyngeal transit times for dysphagia evaluation in 15 patients with myopathy. The successful treatment of dysphagia by cricopharyngeal myotomy is reported in two patients with limb-girdle syndrome.     

Prevalence of mabDAS-1 positivity in biopsy specimens from the esophagogastric junction

OBJECTIVE: Intestinal metaplasia (IM) is a precursor for malignancies at the esophagogastric junction. A monoclonal antibody, mAbDAS-1, can probably identify cellular characteristics of IM before the appearance of goblet cells. The aim of this study was to examine the prevalence of mAbDAS-1 positivity in biopsies from the squamocolumnar junction (SCJ) and to correlate this positivity with the presence of IM and clinical findings. METHODS: In 559 patients, reflux symptoms were scored, and the presence of reflux esophagitis and hiatus hernia was evaluated during endoscopy. Two biopsy specimens were obtained from the SCJ. In a subset of patients (n = 99), biopsies from the endoscopically defined cardiac region (2 cm distal to proximal margin of gastric folds) were available. Biopsy specimens were stained with hematoxylin and eosin, Alcian Blue, modified Giemsa, and mAbDAS-1. RESULTS: mAbDAS-1 positivity was observed in the SCJ biopsies of 201 of 486 (41.4%) patients without IM and in 64 of 73 (87.7%) patients with IM. Patients without IM but with antibody positivity showed similar histological characteristics as patients with IM at the SCJ. Biopsies of 123 of 559 patients (22%) revealed a columnar-cuboidal epithelium, which was found to be mAbDAS-1 positive in 64.2% (77 of 123). Tissue specimens from the cardiac region without IM stained positive in 14.2% (13 of 91), 12 of those also stained at the SCJ. CONCLUSIONS: In patients without IM, a high prevalence of mAbDAS-1 positivity was observed. Biopsies of these patients showed similar histological characteristics as patients with IM. Although not all patients exhibiting this reactivity may develop IM, mAbDAS-1 reactivity may help in the understanding of the histogenesis of IM at the SCJ.