Etsuro Yazaki

Transgastric gastropexy and hiatal hernia repair for GERD under EUS control: a porcine model

BACKGROUND Endoluminal operations for gastroesophageal reflux currently are limited by the inability to visualize and manipulate structures outside the wall of the gut. This may be possible by using EUS. The aims of this study were the following: to define the EUS anatomy of structures outside the gut that influence reflux, to place stitches in the median arcuate ligament, to perform posterior gastropexy, and to test the feasibility of crural repair under EUS control in pigs. METHODS In survival experiments in 22 pigs, by using a linear-array echoendoscope, the median arcuate ligament and part of the right crus were identified and punctured with a needle, which served as a carrier for a tag and thread. These were anchored into the muscle. An endoscopic sewing device was used, allowing stitches to be placed through a 2.8-mm accessory channel to any predetermined depth. New methods allowed knot tying and thread cutting through the 2.8-mm channel of the echoendoscope. RESULTS Stitches were placed through the gastric wall into the median arcuate ligament, and one stitch was placed just beyond the wall of the lower esophageal sphincter. The stitches were tied together and locked against the gastric wall. Median lower esophageal sphincter pressure, determined manometrically, was 11 mm Hg before surgery and 21 mm Hg after stitch placement (p=0.0002). The length of the lower esophageal sphincter increased from a median of 2.8 cm before the procedure to 3.5 cm after the procedure. At the postmortem, the median force required to pull the tags out of the median arcuate ligament was 2.8 kg. CONCLUSIONS This study demonstrates that transgastric gastroesophageal reflux surgery, by using stitching under EUS control, can significantly increase lower esophageal sphincter pressure in pigs.

Antireflux operations at flexible endoscopy using endoluminal stitching techniques: an experimental study

BACKGROUND Three antireflux operations-gastroplasty, fundoplication, and anterior gastropexy-were developed for performance at flexible endoscopy without laparotomy or laparoscopy. METHODS An endoscopic sewing machine mounted on a standard gastroscope, endoscopic knotting devices, overtube, and nylon thread were used to perform these operations in adult beagle dogs. RESULTS Gastroplasty (n = 10) was accomplished by suturing the anterior and posterior wall of the stomach to create a gastric tube (neoesophagus) along the lesser curve. An anatomic arrangement similar to fundoplication (n = 6) was achieved by invaginating the esophagus and fixing it to the stomach 2 cm distal to the cardioesophageal junction. Anterior gastropexy (n = 6) was performed using a technique similar to that used in creating percutaneous gastrostomies. There was no mortality. Ninety percent of sutures were seen at repeat endoscopy at 4 to 8 week intervals. The gastroplasty group was selected for more extensive evaluation. Manometry using a three-channel perfused catheter system before and after the procedures showed an increase in the lower esophageal sphincter pressure (preoperative median 4.6 mm Hg; post-operative median 13.33 mm Hg, p = 0.008) and cardiac yield pressures (preoperative median 10 mm Hg; postoperative median 19 mm Hg, p = 0.007). CONCLUSIONS This study demonstrates the feasibility of performing antireflux operations at flexible endoscopy, without laparoscopy or laparotomy, by use of endoluminal suturing techniques.

Aetiology of running-related gastrointestinal dysfunction. How far is the finishing line?

Abstract30 to 65% of long distance runners experience gastrointestinal (GI) symptoms related to exercise. Several hypotheses have been postulated; however, the aetiology and pathophysiology are far from clear.The mechanical effect of running on the viscera must be involved in the development of GI symptoms in this sport. Reduction of splanchnic blood flow due to visceral vasoconstriction is another widely supported theory; nevertheless, it does not explain many of the clinical findings. Examination of the GI tract during exercise is a difficult task, and measurements of both orocaecal and whole-gut transit time have shown equivocal results. GI hormones, and especially prostaglandins, may be of crucial importance for the production of symptoms. Intestinal absorption, secretion and permeability may also be altered during exercise, provoking intestinal dysfunction. Factors such as stress, diet, dehydration, infections and other factors need to be analysed in order to present a global view of the hypotheses regarding the aetiology of this common and often overlooked problem.

In vivo evaluation of acid-induced changes in oesophageal mucosa integrity and sensitivity in non-erosive reflux disease

Objective Patients with non-erosive reflux disease (NERD) have impaired oesophageal mucosal integrity (dilated intercellular spaces). Oesophageal mucosal integrity reflects the balance between repeated reflux damage and mucosal recovery. The relationship between mucosal integrity and acid sensitivity is unclear. Oesophageal impedance may be used for in vivo mucosal integrity measurement. We studied acid-induced changes in oesophageal mucosal integrity and acid perception in patients with heartburn. Design 50 patients with heartburn whithout oesophagitis underwent impedance monitoring before, during and after 10 min oesophageal perfusion with neutral (pH6.5) and acid solutions (pH1). Symptoms and impedance were recorded during perfusion. Impedance recovery was assessed for 2 h post-perfusion in ambulatory conditions followed by 24-h impedance-pH study. Results Reflux monitoring discriminated 20 NERD and 30 functional heartburn (FH) patients. Neutral perfusion caused impedance fall that recovered within 10 min. Acid perfusion caused impedance fall with slow recovery: 6.5 Ω/min (IQR 3.3-12.0 Ω/min). Patients with slow recovery (<25th percentile) had lower baseline impedance (1273 Ω ±208 Ω vs. 3220 Ω ±275 Ω ±, p < 0.01) and more frequent acid sensitivity (10/12 vs. 4/12, p = 0.04) than those with fast (>75th percentile) recovery. Patients with NERD had lower baseline impedance (1669 ± 182 Ω vs. 2384 ± 211 Ω, p = 0.02) and slower impedance recovery (6.0 ± 0.9 Ω/min vs. 10.7 ± 1.6 Ω/min, p = 0.03) than patients with FH. Conclusion Impaired mucosal integrity might be the consequence of repeated reflux episodes with slow recovery. Mucosal integrity, recovery capacity and symptom perception are linked. Low basal impedance and slow recovery after acid challenge are associated with increased acid sensitivity.

The role of gastrointestinal endoscopy in long-distance runners with gastrointestinal symptoms.

Background Exercise-related gastrointestinal symptoms are not uncommon among athletes. The occurrence of gastrointestinal bleeding has been reported, especially in long-distance runners. We studied gastrointestinal mucosal damage, using gastrointestinal endoscopy, in competitive long-distance runners. Gastrointestinal blood loss and anaemia before and after running were also assessed. Methods Sixteen competitive long-distance runners (all men; age range 16–19 years) participated in the study. All runners completed a symptom questionnaire prior to a 20 km race. Stool occult blood and haematological studies (haemoglobin, haematocrit, serum iron, total iron-binding capacity [TIBC] and ferritin) were performed before and immediately after the race. Gastrointestinal endoscopy was performed to assess macroscopic changes. Colonoscopy was also performed on the patients who had positive stool occult blood before or after the race. Results Gastrointestinal symptoms were frequently experienced by the runners. Gastritis (n = 16), oesophagitis (n = 6) and gastric ulcer (n = 1) were found at gastroscopy. Colonoscopy was performed on four patients who had positive stool occult blood. One had multiple erosions at the splenic flexure and one had a rectal polyp. Five runners had anaemia, and all of these had at least one endoscopic lesion (three gastritis, two oesophagitis and one multiple erosion at the splenic flexure). There were significant changes in the following haematological parameters after the race: iron (decreased, P = 0.02), ferritin (decreased, P = 0.001) and TIBC (increased, P = 0.00005). Conclusions Gastrointestinal symptoms and gastrointestinal mucosal damage are prevalent among long-distance runners. Prior to treatment, gastrointestinal endoscopy should be considered in long-distance runners with gastrointestinal symptoms and/or anaemia.

An ambulant porcine model of acid reflux used to evaluate endoscopic gastroplasty

BACKGROUND There is a lack of suitable models for testing of therapeutic procedures for gastro-oesophageal reflux disease. Endoscopic sewing methods might allow the development of a new less invasive surgical approach to treatment of gastrointestinal disorders. AIMS To develop an animal model of gastro-oesophageal reflux for testing the efficacy of a new antireflux procedure, endoscopic gastroplasty, performed at flexible endoscopy without laparotomy or laparoscopy. METHODS At endoscopy a pH sensitive radiotelemetry capsule was sewn to the oesophageal wall, 5 cm above the lower oesophageal sphincter, in six large white pigs. Ambulant pH recordings (48–96 hours; total 447 hours) were obtained. The median distal oesophageal pH was 6.8 (range 6.4–7.3); pH was less than 4 for 9.3% of the time. After one week, endoscopic gastroplasty was performed by placing sutures below the gastro-oesophageal junction, forming a neo-oesophagus of 1–2 cm in length. Postoperative manometry and pH recordings (24–96 hours; total 344 hours) were carried out. RESULTS Following gastroplasty, the median sphincter pressure increased significantly from 3 to 6 mm Hg and in length from 3 to 3.75 cm. The median time pH was less than 4 decreased significantly from 9.3% to 0.2%. CONCLUSIONS These are the first long term measurements of oesophageal pH in ambulant pigs. The finding of spontaneous reflux suggested a model for studying treatments of reflux. Endoscopic gastroplasty increased sphincter pressure and length and decreased acid reflux.

Pepsin in saliva for the diagnosis of gastro-oesophageal reflux disease

Objective Current diagnostic methods for gastro-oesophageal reflux disease (GORD) have moderate sensitivity/specificity and can be invasive and expensive. Pepsin detection in saliva has been proposed as an ‘office-based’ method for GORD diagnosis. The aims of this study were to establish normal values of salivary pepsin in healthy asymptomatic subjects and to determine its value to discriminate patients with reflux-related symptoms (GORD, hypersensitive oesophagus (HO)) from functional heartburn (FH). Design 100 asymptomatic controls and 111 patients with heartburn underwent MII-pH monitoring and simultaneous salivary pepsin determination on waking, after lunch and dinner. Cut-off value for pepsin positivity was 16 ng/mL. Patients were divided into GORD (increased acid exposure time (AET), n=58); HO (normal AET and + Symptom Association Probability (SAP), n=26) and FH (normal AET and—SAP, n=27). Results 1/3 of asymptomatic subjects had pepsin in saliva at low concentration (0(0–59)ng/mL). Patients with GORD and HO had higher prevalence and pepsin concentration than controls (HO, 237(52–311)ng/mL and GORD, 121(29–252)ng/mL)(p<0.05). Patients with FH had low prevalence and concentration of pepsin in saliva (0(0–40) ng/mL). A positive test had 78.6% sensitivity and 64.9% specificity for diagnosis of GORD+HO (likelihood ratio: 2.23). However, one positive sample with >210 ng/mL pepsin suggested presence of GORD+HO with 98.2% specificity (likelihood ratio: 25.1). Only 18/84 (21.4%) of GORD+HO patients had 3 negative samples. Conclusion In patients with symptoms suggestive of GORD, salivary pepsin testing may complement questionnaires to assist office-based diagnosis. This may lessen the use of unnecessary antireflux therapy and the need for further invasive and expensive diagnostic methods.

Relationship between symptom response and oesophageal acid exposure after medical and surgical treatment for gastro-oesophageal reflux disease.

The relationship between symptom severity and objective evidence of gastro‐oesophageal reflux disease (GORD) after medical and surgical treatment has recently been questioned. This study aimed to compare the symptomatic and physiological response (as measured by pHmetry) to the treatment of GORD by proton pump inhibitors (PPIs) and by laparoscopic antireflux surgery, and to examine the relationship between the patients subjective and objective response to treatment of GORD.

Accurate localization of a fall in pH within the ileocecal region: validation using a dual-scintigraphic technique

Stereotypical changes in pH occur along the gastrointestinal (GI) tract. Classically, there is an abrupt increase in pH on exit from the stomach, followed later by a sharp fall in pH, attributed to passage through the ileocecal region. However, the precise location of this latter pH change has never been conclusively substantiated. We aimed to determine the site of fall in pH using a dual-scintigraphic technique. On day 1, 13 healthy subjects underwent nasal intubation with a 3-m-long catheter, which was allowed to progress to the distal ileum. On day 2, subjects ingested a pH-sensitive wireless motility capsule labeled with 4 MBq (51)Chromium [EDTA]. The course of this, as it travelled through the GI tract, was assessed with a single-headed γ-camera using static and dynamic scans. Capsule progression was plotted relative to a background of 4 MBq ¹¹¹Indium [diethylenetriamine penta-acetic acid] administered through the catheter. Intraluminal pH, as recorded by the capsule, was monitored continuously, and position of the capsule relative to pH was established. A sharp fall in pH was recorded in all subjects; position of the capsule relative to this was accurately determined anatomically in 9/13 subjects. In these nine subjects, a pH drop of 1.5 ± 0.2 U, from 7.6 ± 0.05 to 6.1 ± 0.1 occurred a median of 7.5 min (1-16) after passage through the ileocecal valve; location was either in the cecum (n = 5), ascending colon (n = 2), or coincident with a move from the cecum to ascending colon (n = 2). This study provides conclusive evidence that the fall in pH seen within the ileocolonic region actually occurs in the proximal colon. This phenomenon can be used as a biomarker of transition between the small and large bowel and validates assessment of regional GI motility using capsule technology that incorporates pH measurement.

Objective evaluation of small bowel and colonic transit time using pH telemetry in athletes with gastrointestinal symptoms

Background: Gastrointestinal (GI) disturbances are often reported by long distance runners and are more common in women, particularly after prolonged high intensity exercise. Objectives: To determine whether these symptoms could be associated with alterations in GI motility. Methods: Small bowel and colonic transit were measured using pH telemetry in a group of 11 female athletes (age 22 to 53 years), six of whom experienced lower GI symptoms during exercise. Subjects participated in two experimental sessions: a control measurement, where small bowel transit was estimated during a rest period (R) of six hours; and an exercise session (E), where small bowel transit was measured during a one hour period of high intensity exercise (cross country running) at >70% V˙O2max. Colonic transit was estimated indirectly from determinations of whole gut transit time by radio-opaque marker. Results: Small bowel transit time was 3.5 to 10.6 h (R) and 3.0 to 8.7 h (E) in asymptomatic athletes, versus 4.0 to 6.6 h (R) and 4.6 to 7.3 h (E) in symptomatic athletes (NS). Colonic transit time was 35.0 to 62.5 h (R) and 30.5 to 70.9 h (E) in asymptomatic athletes versus 20.4 to 42.9 h (R) and 21.5 to 67.2 h (E) in symptomatic athletes (NS). Conclusions: Small bowel and colonic transit times were similar in the two groups in the rest and exercise sessions. The diarrhoea seen in this study did not result from accelerated colonic transit. Other mechanisms must be sought.