T. R. DeMeester

A New Technique for Measurement of Pharyngeal pH: Normal Values and Discriminating pH Threshold

IntroductionIdentifying gastroesophageal reflux disease as the cause of respiratory and laryngeal complaints is difficult and depends largely on the measurements of increased acid exposure in the upper esophagus or ideally the pharynx. The current method of measuring pharyngeal pH environment is inaccurate and problematic due to artifacts. A newly designed pharyngeal pH probe to avoid these artifacts has been introduced. The aim of this study was to use this probe to measure the pharyngeal pH environment in normal subjects and establish pH thresholds to identify abnormality.MethodsAsymptomatic volunteers were studied to define the normal pharyngeal pH environment. All subjects underwent esophagram, esophageal manometry, upper and lower esophageal pH monitoring with a dual-channel pH catheter and pharyngeal pH monitoring with the new probe. Analyses were performed at 0.5 pH intervals between pH 4 and 6.5 to identify the best discriminating pH threshold and calculate a composite pH score to identify an abnormal pH environment.ResultsThe study population consisted of 55 normal subjects. The pattern of pharyngeal pH environment was significantly different in the upright and supine periods and required different thresholds. The calculated discriminatory pH threshold was 5.5 for upright and 5.0 for supine periods. The 95th percentile values for the composite score were 9.4 for upright and 6.8 for supine.ConclusionA new pharyngeal pH probe which detects aerosolized and liquid acid overcomes the artifacts that occur in measuring pharyngeal pH with existing catheters. Discriminating pH thresholds were selected and normal values defined to identify patients with an abnormal pharyngeal pH environment.

Safety analysis of first 1000 patients treated with magnetic sphincter augmentation for gastroesophageal reflux disease.

Antireflux surgery with a magnetic sphincter augmentation device (MSAD) restores the competency of the lower esophageal sphincter with a device rather than a tissue fundoplication. As a regulated device, safety information from the published clinical literature can be supplemented by tracking under the Safe Medical Devices Act. The aim of this study was to examine the safety profile of the MSAD in the first 1000 implanted patients. We compiled safety data from all available sources as of July 1, 2013. The analysis included intra/perioperative complications, hospital readmissions, procedure-related interventions, reoperations, and device malfunctions leading to injury or inability to complete the procedure. Over 1000 patients worldwide have been implanted with the MSAD at 82 institutions with median implant duration of 274 days. Event rates were 0.1% intra/perioperative complications, 1.3% hospital readmissions, 5.6% endoscopic dilations, and 3.4% reoperations. All reoperations were performed non-emergently for device removal, with no complications or conversion to laparotomy. The primary reason for device removal was dysphagia. No device migrations or malfunctions were reported. Erosion of the device occurred in one patient (0.1%). The safety analysis of the first 1000 patients treated with MSAD for gastroesophageal reflux disease confirms the safety of this device and the implantation technique. The overall event rates were low based on data from 82 institutions. The MSAD is a safe therapeutic option for patients with chronic, uncomplicated gastroesophageal reflux disease.

Ultrasonic epithelial ablation of the lower esophagus without stricture formation. A new technique for Barrett's ablation.

AbstractBackground: The premalignant potential of Barrett’s esophagus has stimulated efforts to find a way to ablate the columnar epithelium in order to reheal the area with squamous epithelium, thus obviating the cancer risk. This study describes and evaluates a new technique using ultrasonic energy to ablate the epithelium of the lower esophagus in a porcine model. Methods: Eight young farm pigs were used to develop the technique of applying a laparoscopic Cavitron Ultrasonic Surgical Aspirator (CUSA) to the lower esophageal mucosa through an operating gastrostomy. A further 11 Yakutan minipigs then underwent CUSA epithelial ablation, followed by a laparoscopic Nissen fundoplication or postoperative acid suppression therapy. We then assessed the healing response in these subjects. Results: Optimal CUSA energy settings enabled complete ablation of the squamous epithelium with preservation of the muscularis mucosa and submucosa. The integrity of the aspirated cells was sufficient for cytological analysis. Healing occurred by squamous regeneration without stricture formation. Conclusions: The CUSA technique holds promise for complete ablation of the Barrett’s epithelium in a single setting. The unique tissue-selective nature of the ablative process allows complete mucosal reepithelialization without stricture formation.

Redefining gastroesophageal reflux (GER).

Background: The detection of gastroesophageal reflux (GER) has to date been limited to acid exposure observed on 24-h pH monitoring. It is clear, however that nonacid reflux can be a significant clinical problem. Recently, as impedance technology with the capacity to detect all types of reflux (acid, nonacid, liquid, mixed, and air) has been developed. Methods: Seventeen asymptomatic healthy volunteers underwent combined 24-h pH and impedance testing. In all patients, pH was measured at 5 cm above the lower esophageal sphincter (LES), and simultaneous impedance changes were recorded at 3, 5, 7, 9, 15, and 17 cm above the LES. Refluxes were classified as acid (drop in pH <4 for >5 sec), Nonacid, short acid, or nonacid delta based on chemical properties; they were further classified as liquid, mixed, or gas based on the physical refluxate detected by impedance changes. The height of the reflux entering the esophagus was classified as distal (<5 cm), intermediate (5–9 cm), or proximal (9–17 cm). Results: A total of 868 reflux events were characterized. Fifty-nine percent of them were not conventional acid reflux and could only be detected by impedance changes. Less than 2% of the events that were detected by a fall in pH to <4 were not detected by impedance changes. Pure liquid reflux was seen in 35.4%, a mixed pattern in 36.3%, and a gas reflux in 26.7%. Liquid was confined to the distal esophagus in 30%; it reached the midesophagus in 58% and the proximal esophagus in 11%. Conclusions: Over half of GER events are not detected by pH studies. Liquid reflux reaches the mid and proximal esophagus 69% of the time and gas nearly always does (92%). The additional information provided by impedance technology is likely to have a major impact on the understanding and clinical management of patients with gastroesophageal reflux disease (GERD).

Etiology of intestinal metaplasia at the gastroesophageal junction

Background: Intestinal metaplasia occurs in the esophagus as a consequence of gastroesophageal reflux disease and in the stomach secondary to H. pylori infection. The etiology of intestinal metaplasia limited to the gastroesophageal junction or cardia (CIM) is disputed. We hypothesized that CIM has dual etiologies: gastroesophageal reflux in some, H. pylori infection in others, and that cytokeratin immunostaining can help to differentiate between these two etiologies. Methods: We defined CIM as the presence of intestinal metaplasia within cardiac mucosa on biopsy from an endoscopically normal-appearing gastroesophageal junction. Thirty patients with CIM who had multiple biopsy specimens taken from the esophagus, gastroesophageal junction, and stomach were identified. Tissue blocks from biopsy specimens taken at the gastroesophageal junction were sectioned and immunostained for cytokeratins 7 and 20. The cytokeratin 7/20 staining of the CIM in each patient was determined to be either a Barretts or non-Barretts pattern. H. pylori infection was assessed by Giemsa staining of antral biopsy specimens. Results: H. pylori infection was present in 16 patients. A Barretts cytokeratin 7/20 staining pattern in the CIM was present in only 46% of the H. pylori–positive patients, as compared to 86% in the 14 patients with CIM and no H. pylori (p = 0.025). Objective evidence of reflux disease was present in 71% of patients with CIM and no H. pylori, as compared to 31% of patients with H. pylori. Conclusions: The two different patterns of cytokeratin 7/20 staining found in patients with CIM support the concept of dual etiologies for CIM. A Barretts staining pattern was associated with objective evidence of gastroesophageal reflux and the absence of H. pylori, suggesting that cytokeratin 7/20 immunostaining is useful to determine the likely etiology of CIM.

Esophagectomy for cancer in octogenarians.

Because of changes in life expectancy, there is an increasing number of elderly patients with esophageal cancer. The aim of this study was to assess the outcome of esophagectomy for cancer in patients 80 years or older. A retrospective review was performed of the records of all patients who underwent esophagectomy for cancer from 1992 to 2007. A cardiac and pulmonary evaluation was obtained on an individual basis in the younger patients and in all octogenarians. Among 560 patients with esophagectomy for cancer, 47 patients (8%) were octogenarians. The median age of the younger group (n= 513) was 63 years (interquartile range 56-71). Octogenarians had significantly more stage III disease (49% vs 31%, P= 0.02) but received less neoadjuvant therapy than younger patients (2% vs 21%, P= 0.0004). In octogenarians, the transhiatal resection was more common than in the younger group (79% vs 36%, P < 0.0001). Weight loss prior to surgery was similar in both groups, but body mass index was significantly lower in octogenarians (25 vs 28 kg/m(2) , P= 0.0002). Major complications occurred in 26% in octogenarians and 31% in the younger group (P= 0.51). Hospital mortality was similar (9% for octogenarians vs 4% in the younger group, P= 0.13). The median postoperative hospital stay was similar at 16 days (P= 0.69). There was no difference in cancer-related survival (median survival 48.9 vs 59.3 months, P= 0.31 log-rank test). Esophagectomy can be performed safely in carefully selected octogenarians with good cardiac and pulmonary function. Patients should not be denied an esophagectomy based only on their age.

Gastro-esophageal reflux disease confined to the sphincter*

SUMMARY. It has been shown previously that patients with gastro-esophageal reflux disease (GERD) do not always have increased esophageal acid exposure on 24 h pH monitoring. The recent recognition of carditis as a sensitive marker for GERD raises the possibility for patients with mild disease to have normal esophageal acid exposure but inflamed cardiac mucosa on biopsies of the cardia, which may be an early sign of GERD. To test this hypothesis, 171 consecutive patients evaluated for symptoms of GERD and no increased esophageal acid exposure, Barrett’s esophagus or erosive esophagitis were divided into those with and without carditis. Esophageal acid exposure and lower esophageal sphincter (LES) characteristics were compared between the two groups. Comparisons were done using the Mann‐Whitney U-test for non-parametric data. There were 82 patients with histologic evidence of carditis and 89 patients without carditis. Patients with carditis had a more deteriorated sphincter, determined by overall and abdominal length and resting pressure, and significantly higher esophageal acid exposure (P < 0.05). Patients with symptoms of GERD and histologic evidence of carditis may have early or mild reflux disease, which is confined to the sphincter.

Circular stapled pyloroplasty: a fast and effective technique for pyloric disruption during esophagectomy with gastric pull-up.

The necessity of pyloroplasty after esophagectomy and gastric pull-up is debated. Disadvantages of a standard pyloroplasty include the potential for leak, shortening of the length of the graft, and complexity when done during a minimally invasive procedure. The aim of this study is to report our experience with a novel internal pyloroplasty technique using a circular stapler (CS pyloroplasty), which is applicable for both laparoscopic and open esophagectomy. The records of all patients who underwent an esophagectomy with gastric pull-up and pyloroplasty between 2002 and 2007 were reviewed. The CS pyloroplasty was performed through a lesser curve gastrotomy with a 21-mm CS, while the standard pyloroplasty entailed a longitudinal full thickness incision through the pylorus with mucosal closure in the same direction and a Graham patch. A CS pyloroplasty was performed in 144 and a standard pyloroplasty in 133 patients. The median patient age was 66years, and the median follow-up was 17months, and was similar for both types of pyloroplasty. Routine postoperative videoesophagram was significantly more likely to show a delay in contrast transit through the pylorus after standard pyloroplasty (16% standard vs. 8% CS pyloroplasty, P= 0.03). Significantly more patients had postoperative endoscopy after standard pyloroplasty (40% standard vs. 24% CS pyloroplasty, P= 0.004), but the frequency of pyloric dilatation was similar. There were no leaks with either technique. A circular stapled pyloroplasty is as efficacious as a standard pyloroplasty after esophagectomy with gastric pull-up. Potential advantages include the ease and simplicity of the procedure along with virtually no risk of a leak and no graft shortening. The technique is amenable to both open and minimally invasive procedures.

The gene expression profile of cardia intestinal metaplasia is similar to that of Barrett's esophagus, not gastric intestinal metaplasia

The etiology and significance of cardia intestinal metaplasia (CIM) is disputed. CIM may represent a form of Barretts esophagus due to reflux or could reflect generalized gastric intestinal metaplasia due to Helicobacter pylori. The aim of this study was to utilize gene expression data to compare CIM to Barretts and gastric intestinal metaplasia. Endoscopic biopsies were classified by endoscopic and histologic criteria as CIM (n= 33), Barretts (n= 25), or gastric intestinal metaplasia of the antrum or body (n= 18). The squamocolumnar and gastroesophageal junctions were aligned in CIM patients and patients with diffuse gastric intestinal metaplasia were excluded. H. pylori was tested for in the biopsies of all patients. After laser-capture microdissection, quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the mRNA expression of a panel of nine genes that has been shown to differentiate Barretts from other foregut mucosa. Cluster analysis with linear discriminant analysis of the expression data was used to classify each sample into groups based solely on similarity of gene expression. Cluster analysis was performed for three groups (CIM vs. Barretts vs. gastric intestinal metaplasia) and two groups (CIM + Barretts vs. gastric intestinal metaplasia). There was no difference in H. pylori infection among groups (P= 0.66). Clustering into three groups resulted in frequent misclassification between CIM and Barretts while misclassification of gastric intestinal metaplasia was uncommon. The CIM and Barretts groups were then combined for two group clustering and linear discriminant analysis correctly predicted 95% of CIM and Barretts samples and 83% of gastric intestinal metaplasia samples based on gene expression alone. In conclusion, the gene expression profiles of CIM and Barretts esophagus were similar in 95% of biopsies and differed significantly from that of gastric intestinal metaplasia. The indistinguishable gene expression profile of CIM and BE suggests that they may share a common etiology in the majority of patients with a similar biology, and calls into question the perception that CIM is an innocuous process.

Can clinical and endoscopic findings accurately predict early-stage adenocarcinoma?

BackgroundThe presentation and management of esophageal cancer are changing, as more patients are diagnosed at an earlier stage of the disease in which endoscopic treatment methods may be contemplated. Therefore, we conducted a study to determine whether symptomatic and endoscopic findings can accurately identify node-negative early-stage adenocarcinoma.MethodsA total of 213 consecutive patients (171 men and 42 women) with resectable esophageal adenocarcinoma seen from 1992 to 2002 were evaluated. None of these patients received neoadjuvant chemotherapy or radiation therapy. Using a multivariable model, model-based probabilities of early-stage disease (T1 im/sm N0) were calculated for each combination of the following three features: no dysphagia as main symptom at presentation, tumor length ≤2 cm, and noncircumferential lesion.ResultsEighty-two percent of the patients with all three characteristics presented with early-stage disease. Even in the setting of small, visible, noncircumferential tumors/nodules in patients without dysphagia, 14% of the patients harbored node metastasis.ConclusionsSimple clinical and endoscopic findings predicted early-stage disease in 82% of cases, whereas a small but significant percentage had node metastasis. Because node metastasis predisposes to local failure in nonresectional treatment options such as endoscopic mucosal resection and photodynamic therapy, such findings should have a significant bearing on treatment decisions.