EP4673084A1

EP4673084A1 - Medical device of implanting gastroesophageal anti-reflux and obesity devices in an esophagus

Info

Publication number: EP4673084A1
Application number: EP24715965.0A
Authority: EP
Inventors: Norman Godin
Original assignee: Biomedix SA Switzerland
Current assignee: Biomedix SA Switzerland
Priority date: 2023-02-28
Filing date: 2024-02-27
Publication date: 2026-01-07
Also published as: WO2024182352A1

Abstract

A method of preventing contraction and peristaltic wave action of an esophagus in which a GARD is placed and preventing displacement of the GARD towards or into a stomach can include injecting botulinum toxin in the muscular layer of the esophageal wall at the level where the GARD is or will be placed. A system can include a catheter device for orienting an injection and allowing injection of botulinum toxin at a selected depth in the esophagus to reach the muscular layer around the circumference of the esophagus to block peristalsis. A system can include a GARD having a ring maintained in a folded state with a thread tied with a draw string knot. The draw string knot can be adapted to be untied by pulling on a string from a distance, thereby allowing the ring to unfold.

Description

MEDICAL DEVICE AND METHOD OF IMPLANTING GASTROESOPHAGEAL ANTIREFLUX AND OBESITY DEVICES IN AN ESOPHAGUS

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present application claims priority to U.S. Provisional Application No. 63/448,709, filed February 28, 2023, the entire disclosure of which is hereby incorporated by reference in its entirety.

SUMMARY

[0002] The presently disclosed technology relates to the field of medical devices, particularly medical devices relating to gastroenterology, and more specifically to apparatus and methods of implanting gastroesophageal anti-reflux devices (“GARDS™”) and or obesity devices in an esophagus.

[0003] The term GARD™ can also refer to a gastro-intestinal anti-reflux device.

[0004] GARDS™ are thin walled tubular medical devices placed in the esophagus. GARDs can be placed in the esophagus or extend from the esophagus into the stomach with a top ring that is calibrated precisely to the millimeter to the diameter of the esophagus with a calibration balloon that is passed through the working channel of the endoscope at the level of the lower third of the body of the esophagus under visual control of the gastroscope to determine the diameter of the esophagus once opened. Thus, the calibration balloon can measure the diameter of the esophagus. A guide-wire can be passed through the working channel of the endoscope at the level of the lower third of the body of the esophagus under visual control and the distance is measured between the upper dental arch of the gastroscope to 5 cm above the Z-line. to determine the diameter of the esophagus once opened and air is blown in the balloon until resistance is felt and confirmed on the manometer placed on the proximal end of the calibration balloon, (new). The volume of air injected is measured.

[0005] Alternatively, a guide-wire can be placed under endoscopic vision through the esophagus into the stomach. The gastroscope can then be removed from the esophagus while the guide -wire is kept in position in the esophagus down to the stomach. The calibration balloon can be placed blindly over the guide- wire to about 30 cm of the upper dental arch and the gastroscope can then be reinserted through the mouth next (in a parallel position) to the guide-wire and the calibration balloon. The calibration balloon under endoscopic vision can be placed over the guide-wire about 5 cm above the Z line (e.g., the junction of the stomach and esophagus mucosae) and inflated with air to a maximum volume of air with a syringe outside the patient’ s body (where the manometer is also placed) until the balloon is blocked in the esophagus and cannot be pushed or pulled any more. The volume of air inflated can be carefully measured and an increase in pressure of the manometer also confirmed. The balloon can then be deflated, pulled out of the patient’ s body, then reinflated outside the body with the same maximum volume of air and pressure and the diameter is carefully measured with the calibration card. This measurement can determine the maximum diameter of the dilated esophagus which corresponds to the base size of the GARD diameter and the diameter of the stent device that will normally be of the same size, at most 3 mm more or less then this base esophageal diameter, but usually the same size or 1 mm more or less depending on the evaluation of the endoscopist, the local anatomy and the strategy of pose chosen (see, e.g., FIGS. 15A, 15B, 15C, and 16). This measurement of the diameter of the esophagus with the calibration balloon and confirmed by pressure increase in the manometer determines the diameter of the esophagus for each given patient and therefore the size of the DM-GARD and the Th-GARD. The end result of the procedure can depend on a very careful calibration and the selection of the right sizes of DM- GARD and Th-GARD and has to be done at least a week before planning the therapy when a pH metric study is done at the same time as calibration to confirm the GERD (gastroesophageal reflux). [0006] Alternatively, the calibration balloon is opened up to the point where three arms of the calibration balloon are in contact with the wall of the esophagus, the size is marked on the handle of the calibration balloon then the calibration balloon is closed, removed from the working channel of the gastroscope and is reopened to the same opening outside the patient. In order to determine the appropriate size ring, usually between 20 mm and 30 mm of diameter, the calibration balloon is reopened to the same size measured in the esophagus and a calibration card (or a calibration block that has the depth of the vertical part of the balloon that is parallel to the balloon catheter (see 38 in FIGS. 15B and 15C), which is usually 1 to 2 centimeters deep (approximately 0.5 to 1 inch deep thick)). Sizing holes can be used to determine to the millimeter the size of the GARD™ device needed for a given patient.

[0007] The Diagnosis and Management GARD™ (“DM-GARD™”) has a tube in the range of 5 cm to 10 cm, preferably 7.5 cm, long with a 2.5 cm long ring for a total length of 7.5 to 12.5 cm, preferably 10 cm, wherein the thin-walled tube will fold onto itself during reflux back-pressure and will straighten back into the original position spontaneously when the back-pressure stops and is indicated to diagnose gastro-esophageal reflux disease (“GERD”) not responding to Proton Pump Inhibitors (PPIs), defined as “Refractory GERD.” As the DM-GARD™ is a mechanical device, all refluxate that is acid, bile, mixed, and/or gastric enzymes that reflux from the stomach into the esophagus will be blocked while PPIs which are widely used to treat GERD will only help to treat acid reflux but do poorly with other kinds of reflux. Also, it is known that the volume of reflux is the same when the patients take PPIs even when the content is less acid. Up to 30% of patients who have GERD do not respond well or not at all to PPIs and are diagnosed as having Refractory GERD. These patients have no treatment as they do not respond to PPIs as a rule. Surgeons avoid operating on patients who do not respond to PPIs, fearing that the patients will be worse off after surgery as the diagnosis is unclear. Also, about 1% of the population has Laryngo-Pharyngeal Reflux (LPR), which is reflux content reaching the larynx causing chronic sore throat, chronic cough, voice changes affecting quality of life and often affecting careers where oral communication is important. In many cases, high dose PPIs corresponding to the double of a normal 40 mg Nexium (esomeprazole) pill will be prescribed to these LPR patients for 8 to 12 weeks with no effect on the LPR symptoms. pH-impedance tests can demonstrate reflux in these patients if there is high volume but the quality of the refluxate is poorly changed with PPIs, particularly when there is bile reflux. The DM-GARD™ can be expected to help these patients when implanted for longer periods of time as the device is purely mechanical and stops all refluxate mechanically without distinction of pH or volume of the refluxate content.

[0008] A DM-GARD™ placed temporarily for less than a month, usually one week, can help the doctor and patient decide if a longer, slightly more invasive device, called the Therapeutic GARD™, should be placed in a given patient for a much longer period of time. The GARD™ family of devices is the only method that allows a trial period with a temporary device, namely the DM-GARD™ to help determine if the patient should be managed with the DM-GARD™ and help avoid implanting a device that would not be helpful as can happen in the case of surgery or other non-medication based treatments for GERD. The main difference between the temporary DM- GARD™ and the Therapeutic GARD™ is that the DM-GARD™ can have a thicker ring with a nitinol helical spring, as described in U.S. Patent No. 9,572,701, which is incorporated herein by reference, while the Therapeutic GARD™ can have a much thinner ring that can incorporate in the wall of the esophagus, as described in International Publication No. WO 2018/222819, which is incorporated herein by reference. Alternatively, it can be attached to the permanent stent placed in or against the esophageal wall. The stent is a permanent structure placed in (against) or haff inside the wall of the esophagus-half in the lumen of the esophagus that allows attachment of the Therapeutic GARD™ of different shapes and sizes with different functions (tubular GARD™ for more severe reflux for patients who never (or very rarely vomit)). Longer tubular GARDs also known as Obesity GARDs of different length can be adapted to the patients weight loss needs (depending on the Body Mass Index or BMI). The longer the tube, the more restriction there will be to the patient’s eating habits and vice-versa. After the patient has lost some weight, it is possible to “wean” the patient from a longer OB tube to a shorter OB tube then remove the OB tubes entirely with an accompanying diet and regular visits to a dietician. [0009] The OB-GARD™ has tubes longer than 7.5 cm, usually from 10 cm to more than 30 cm and reaching well into the stomach which, in addition of blocking reflux, will force patients to eat small quantities at the time, chew their food better, and eat more slowly, leading to earlier satiety as the food passes through the length of the tubes and helping the patients to lose weight with appropriate diets. Longer tubes reaching through the stomach can reversibly mimic the second most common bariatric operation, namely the “sleeve" gastrectomy, where three quarters of the stomach are definitively removed along the greater curvature of the stomach, leaving a “sleeve” along the lesser curvature of the stomach. The OB-GARD™, as the Therapeutic GARD™, also has a thinner ring capable of integration in the esophageal wall with additional features and techniques.

[0010] Alternatively, the OB-GARD™ can have a distal end that stays in the stomach and a second prepyloric placed tubular device that has been described in other patents by other authors will add the malabsorption factor to endoscopic treatments for obesity.

[0011] The tube of the OB-GARD™ does not require such surgery as the OB-GARD™ is placed through the mouth of the patient. To keep the GARD™ family of devices in place, a ring at the top, or proximal end, of the device is placed in the lower third of the esophagus, more precisely in the last 5 cm of the esophagus above the Z line or esogastric junction. The presence or absence of a hiatus hernia does not affect the use of the GARD™ family of devices as it can in other endoscopic treatments available. Even longer OB-GARDs™ going through the stomach into the duodenum and jejunum can be considered mimicking the effect of the most efficient present bariatric operation, namely the gastric by-pass operation as an internal tube in the duodenum and small bowel would hold the food separately from all the gastric, bowel, bile and pancreatic secretions and enzymes helping the patient lose weight, which is done presently only through major surgery in high risk morbidly obese patients. However, as mentioned above, some of the potential complications of a very long single tube can be prevented by using at least 2 tubular devices. The major advantages of endoscopic devices compared to surgery is that the peri-operative and postoperative morbidity and mortality could be further decreased as well as cost and we could add new aspects to the treatment of type 2 diabetes for the more severe cases thereby reconstituting a more normal metabolism and avoiding long-term increasing additions of high insulin with their potential complications. Also, endoscopic treatment of reflux and/or obesity as both are often linked, will give more flexibility in the treatment by changing the length of the devices if needed (shorter ones if patients lose weight but not enough weight to remove all the devices or longer devices if the patient does not lose enough weight). Of course, diet and participation of the patient is essential as it is known that cultural habits attached to food are of the utmost importance. Early on in the history of surgical obesity, Italian surgeons had successes that could not be reproduced in the U.S. with the same operations. It took time for the doctors to understand that obese Italians ate mainly pasta that has a certain consistency and is a complex carbohydrate, while American obese patients, often teenagers, ate lots of ice cream and candies which have lots of pure sugar and no starch, that avoided the effect of some early by-pass gastric and bowel by-pass operations developed by the Italian surgeons.

[0012] Also, GERD will often appear when patients gain weight. Often as little as a 5 to 10 pound (approximately 3 kg to 5 kg) can be sufficient to cause severe GERD that will improve with weight loss. The GARD™ is the only treatment that addresses both obesity and weight loss.

[0013] However, even with very careful sizing of the ring as described above, if the ring is wide enough to keep the GARD™ in the esophagus, the peristaltic contractions will not automatically push the GARD™ in the stomach but strong peristaltic contractions of the esophagus immediately above the ring will press hard on the top part of the ring of the GARD™ and cause ulcers in the esophageal mucosa at the level of the ring or immediately above as these peristaltic contractions try in vain to push the GARD™ downwards into the stomach. These esophageal ulcers can bleed or lead to perforations. However, above these esophageal ulcers the esophagus is normal.

[0014] There is a need to prevent displacement of a GARD™ from its intended location in the smooth muscle area of the esophagus resulting from contractions and peristaltic wave action without causing ulcerations of the esophageal mucosa.

[0015] Instead of using a more complex catheter as described above that can hurt the patient when passed through the patient’s mouth, pharynx and upper esophagus, a simple injection catheter with a 4 mm to 10 mm long needle when deployed can be employed. With experience, the endoscopist can use the needle to pierce the mucosa right above the ring of the GARD or OB devices and push it anywhere between 1 mm to 5 mm deep, usually 2 mm to 3 mm deep into the mucosa under endoscopic vision and will inject a small dose of botulinum toxin of a about 5 to 20 units, preferably 8 to 10 units aiming for the muscular layer of the esophagus deeper than the mucosa and submucosa but not piercing the esophageal wall. The botulinum toxin can be injected all around the perimeter of the top of the GARD™ ring, usually in 8 to 10 injections of 10 units of botulinum toxin for a total of 100 units of botulinum toxin that has the effect of paralyzing the contractions of the esophagus by blocking locally the muscular layer more distally and the peristaltic wave goes normally from the mouth to the stomach during swallowing. This temporary paralyzing effect of the esophagus right above the placement of the GARD™/OB devices is an essential stage for the long-term placement of the GARD™/OB devices, helping the stent to integrate at least partially the wall of the esophagus and maintain the Therapeutic devices to treat GERD and obesity within the esophageal lumen. [0016] The above-outlined need is addressed by the presently disclosed technology, which can include in one aspect a method of blocking the contractions of the esophagus by injection of botulinum toxin in the wall of the esophagus just above the level where the GARD™ ring will be placed and thereby decreasing or abolishing the peristalsis of the esophagus in the area of the esophagus above where the GARD™ ring will be placed so that a GARD device can remain safely at its intended position for a up to a few months.

[0017] In another aspect the presently disclosed technology can include a system for delivery of the botulinum toxin in the wall of the esophagus at the intended location. The system can include a balloon with a balloon expander orienting guiding tubes for an injection catheter adapted to allow precise injection of Botulinum toxin around the circumference of the esophagus at a selected depth in the esophagus to reach the muscular layer of the esophagus. A further aspect is the injection device can include the catheter having the balloon arranged to block the catheter centrally in the esophagus when expanded so that an injection catheter will reach the esophageal wall at a selected angle for injection of the toxin at a selected depth in the muscular layer of the esophagus.

[0018] A simple injection catheter placed through the working channel of the esophagus with a needle can also be used to inject the botulinum toxin under endoscopic vision.

[0019] Another important advantage of botulinum toxin injection in this indication is that it has a temporary effect of at least 2 to 3 months. This is exactly the time needed to assess the efficacy of the DM-GARD™ that will be placed between 1 week and 4 weeks and then removed. If the DM- GARD™ helps the patient, either the Therapeutic GARD™ (Th-GARD™) can be placed if one treats GERD or the Obesity GARD™ (OB-GARD™) can be inserted with no need to reinject any botulinum toxin. The botulinum toxin by blocking locally peristalsis will allow integration of the Therapeutic GARD™ or the Obesity GARDs™ in the wall of the esophagus for permanent placement. As a potential side-effect of botulinum toxin injection can be some swallowing difficulties, we know that this side -effect is transient even if it turns out with the DM-GARD™ that the patient is not helped by this therapeutic approach and the plan to place the Th-GARD™ or OB- GARD™ is not carried out.

[0020] In one optional embodiment, a system can include a catheter device for orienting an injection and allowing injection, or precise injection, of botulinum toxin at a selected depth in the esophagus to reach the muscular layer around the circumference of the esophagus to block peristalsis. In some embodiments, the catheter will reach the esophageal wall at a predetermined angle and the botulinum toxin injection is injected, optionally precisely, in the muscular layer of the esophagus. [0021] In one optional embodiment, a method for preventing contraction and peristaltic wave action of an esophagus that causes displacement of a medical device from an intended location towards or into the stomach can include injecting botulinum toxin in the wall of the esophagus at the level where the medical device will be placed. This method can include use of any one of the systems as described herein.

[0022] In yet another optional embodiment, a system can include a GARD™ having a ring maintained in a folded state with a thread tied with a draw string knot. The draw string knot can optionally be adapted to be untied by pulling on a string from a distance, thereby allowing the ring to unfold. In some embodiments, the ring unfolds to reach the wall of the esophagus. In some embodiments, the size of the ring is calibrated to the size and location of the esophagus. In some embodiments, the system can further include a catheter for orienting an injection and allowing injection, or even precise injection, of botulinum toxin at a selected depth in the esophagus to reach the muscular layer around the circumference of the esophagus to block peristalsis. In further embodiments, the catheter will reach the esophageal wall at a predetermined angle and the botulinum toxin injection is injected precisely in the muscular layer of the esophagus.

[0023] In still another optional embodiment, a system can be configured to prevent contraction or peristaltic wave action of an esophagus of a patient causing displacement of a gastroesophageal anti-reflux device having a ring used to diagnose and manage refractory Gastroesophageal Reflux Disease (GERD) from an intended location in the esophagus towards or into the stomach. The system can include a catheter having an opening at a proximal end thereof, a port spaced-apart from the opening and located near a proximal end of the catheter, and a plurality of spaced-apart openings in a body thereof. Threads can be configured to enter the catheter at the port and exit the catheter at one of the plurality of spaced-apart openings. Each thread can be configured to be removably attached to the gastroesophageal anti-reflux device.

BRIEF DESCRIPTION OF THE DRAWINGS

[0024] The foregoing summary, as well as the following detailed description of the presently disclosed technology, will be better understood when read in conjunction with the appended drawings, wherein like numerals designate like elements throughout. For the purpose of illustrating the presently disclosed technology, there are shown in the drawings various illustrative embodiments. It should be understood, however, that the presently disclosed technology is not limited to the precise arrangements and instrumentalities shown. In the drawings:

[0025] Figs. 1A-1B are cross-sectional views of a portion of human anatomy including an esophagus and stomach with a perspective view of a GARD™ device according to embodiments of the presently disclosed technology, illustrating the position of the GARD™ device in the lower esophagus. Fig. 1A shows a smooth tubular part 4A of the GARD™ device. Fig. IB shows a lamellar tubular part 4B of the GARD™ device.

[0026] Fig. 2 is an enlarged perspective view of a ring of the GARD™ of one embodiment of the presently disclosed technology and the sites of injection of the botulinum toxin, illustrating a portion of an esophagus in cross-section.

[0027] Fig. 3 is a cross-sectional view from above of the top of the ring as seen with the gastroscope placed in the esophagus.

[0028] Fig. 4 is a side perspective view of an injection balloon catheter of one embodiment of the presently disclosed technology with guiding tubes, before inflation at introduction, partially in cross-section.

[0029] Fig. 5A is a side perspective view of an injection balloon catheter of one embodiment of the presently disclosed technology with the balloon inflated.

[0030] Fig. 5B is a side perspective view of a balloon expander of one embodiment of the presently disclosed technology with three arms spread.

[0031] Fig. 6 is a side perspective view of an injection balloon catheter of one embodiment of the presently disclosed technology with guiding tubes, before inflation, which is a variant of Fig 4 but with a triangular balloon.

[0032] Fig. 7 is a side perspective view of the device of Fig. 6, wherein the triangular balloon is inflated and pushes up the arm of the balloon expander and the end of the guiding tube.

[0033] Fig. 8A is a side perspective view of a GARD™ Introducer with a Botulinum toxin injection catheter of one embodiment of the presently disclosed technology.

[0034] Fig. 8B is a cross-sectional view of the central catheter of Fig. 8A.

[0035] Fig. 8C is cross-sectional view of the central catheter of Fig. 8A with four tubes.

[0036] Fig. 9 is a side perspective view of the device of one embodiment of the presently disclosed technology with threads 25A,B,C pulled out to release the GARD™.

[0037] Fig. 10 illustrates the device of Fig. 9 with the threads 25A,B,C completely pulled out of the catheter.

[0038] Fig. 11 illustrates a combination of a top small triangular, or conical balloon 23 used to spread the arms of the arm expander 22 and the guiding tube 18 and a bottom oval balloon 16 to help deploy the ring of the GARD™ of one embodiment of the presently disclosed technology. [0039] Fig. 12A is a side perspective view of an alternative GARD™ Introducer with a Botulinum toxin injection catheter and with a guide wire according to one embodiment of the presently disclosed technology. [0040] Fig. 12B is a cross-sectional view of the central catheter of Fig. 12A taken from line 12B- 12B of Fig. 12A.

[0041] Fig. 12C is a cross-sectional view of the central catheter of Fig. 12A taken from line 12C- 12C of Fig. 12A.

[0042] Fig. 13 is a side perspective view of the GARD™ Introducer of Fig. 12A with threads untied.

[0043] Fig. 14 is a side perspective view of the GARD™ Introducer of Fig. 12A without the threads or after the threads have been removed from the catheter.

[0044] Fig. 15A is a perspective view of a guide wire within a balloon catheter and a deflated balloon according to one embodiment of the presently disclosed technology.

[0045] Fig. 15B is a perspective view of a guide wire partially surrounded by an inflated balloon and a syringe attached to the balloon catheter and configured to inject air according to one embodiment of the presently disclosed technology.

[0046] Fig. 15C is a perspective view of an embodiment of the presently disclosed technology. [0047] Fig. 16 shows a calibration card or block at ¥i scale according to one embodiment of the presently disclosed technology.

[0048] Fig. 17A is a cross-sectional view of an esophagus, with a GARD™ calibrated ring, a helical spring in the middle of the silicone ring, and a calibration balloon therein.

[0049] Fig. 17B is a cross-sectional view of an esophagus, with a ring of the DM1, DM2, or DM3 model with a helical spring.

[0050] Fig. 17C is a cross-section view of an esophagus wherein a curve therein has disappeared.

DETAILED DESCRIPTION

[0051] While systems, devices and methods are described herein by way of examples and embodiments, those skilled in the art recognize that the presently disclosed technology is not limited to the embodiments or drawings described. Rather, the presently disclosed technology covers all modifications, equivalents and alternatives falling within the spirit and scope of the appended claims.

[0052] The articles “a” and “an” are used herein to refer to one or more than one (i.e., to at least one) of the grammatical object of the article. By way of example, “a cell” means one cell or more than one cell.

[0053] Embodiments described herein as “comprising” one or more features may also be considered as disclosure of the corresponding embodiments “consisting of’ and/or “consisting essentially of’ such features, and vice-versa. [0054] Concentrations, amounts, volumes, percentages and other numerical values may be presented herein in a range format. It is also to be understood that such range format is used merely for convenience and brevity and should be interpreted flexibly to include not only the numerical values explicitly recited as the limits of the range but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range in explicitly recited.

[0055] Features of any one embodiment disclosed herein can be omitted or incorporated into another embodiment.

[0056] Referring first to the drawings which illustrate certain preferred embodiments of the system aspect of the invention, the invention is not limited to any of the illustrated embodiments.

[0057] Figs. 1A and IB show the position of the GARD™ device in the lower esophagus 1. The tubular part 4A (smooth) or 4B (lamellar) of the GARD™ device extends into the stomach 2A, below a hiatus hernia 2B which is part of stomach 2A sliding above the diaphragm 6 in the lower chest as the chest is above the diaphragm. A ring 3A having a top 3C of the GARD™ device includes a helical spring 3B in the lower esophagus 1. The level of the Z line 5 is at the junction of gastric and esophageal mucosa. Diaphragm 6 is shown above stomach 2A. The site 7 of first injections is about 1 cm above the top 3C of the GARD™ ring. Figs. 1A-1B show a GARD™ device which includes a ring 3A which includes top 3C and helical spring 3B in the lower esophagus and 3C top of the ring, the ring 3 A being placed above the level of the Z line 5, which is shown as an irregular line located just at the junction of gastric and esophageal mucosa in the lower esophagus 1. The tubular part 4A or 4B of the GARD™ device extends into stomach 2A.

Diaphragm 6 is located between the lower part of the hiatus hernia 2B and the stomach 2A. The site 7 of the first injections are about 1 cm above the GARD™ ring 3A. Area of enlargement 2 from Figs. 1A and IB is shown in Fig. 2.

[0058] Fig. 2 is an enlarged view of the ring 3A of the GARD™ and the sites 10 of injection indicated by arrows 7 of the botulinum toxin in the muscular layer 9 of the wall of the esophagus. Top 3C of ring 3 A and helical spring 3B are illustrated. Mucosa and submucosa 8 and muscular layer 9 of esophagus 10 are also illustrated. The botulinum toxin is injected in the muscular layer 9, not in the mucosa or submucosa of the esophagus and not through the wall of the esophagus which is easy to do since the whole wall is only 2 to 3 mm thick. Injection of the botulinum toxin has the effect of preventing esophageal peristalsis temporarily (e.g., a few weeks) and will only be used on the final device the Therapeutic GARD, that is the more permanent device to treat Gastroesophageal Reflux Disease (GERD) and/or Obesity placed after the DM-GARD has been removed to help the stent of the Therapeutic GARD integrate in the wall of the esophagus.. [0059] Fig. 3 is a cross-sectional view above the top of the ring as seen with the gastroscope placed in the esophagus showing the top 3C of GARD™ ring 3A in upper view, sites 12 of injection right above the GARD™ ring 3A. In this example, the injections sites are at two levels, immediately above 12 the ring 3 A and 1 cm above 13 the ring 3A. Injecting two levels instead of one level is optional. The end 14 of the tubular part of the GARD™ is seen in perspective.

[0060] Fig. 4 illustrates an injection balloon catheter 15 with guiding tubes 18 before inflation at introduction. Two guiding tubes 18 are shown on both sides of the central catheter 17 for the central guide- wire 17 A and the air inflation for the balloon 17B. A third guiding tube is in the back, not shown since hidden by the central part of the catheter 17. The balloon 16 is not inflated in this view. The tubes 18 act as lumens for guiding tubes for botulinum toxin injection catheters. In Fig.

4 the balloon catheter is placed above and inside the GARD™ ring to guide botulinum toxin injection at the right depth and at even distances around the circumference of the esophagus. The injection catheter can be combined with the delivery or introduction device used to place the GARD™ in the esophagus through the mouth as the same balloon helps deploy the GARD™ ring 3A and insures proper placement of the injection tubes 18 needed for precise botulinum toxin injection in the esophageal wall (See Figures 8, 9 and 10) or two separate catheters can be used, the first one to introduce the GARD™ and the second one to inject the botulinum toxin. Here in Fig. 4 the balloon catheter is separate from the delivery or introduction device. This catheter is used after the GARD™ device has been placed in the esophagus. The catheter has a central lumen used to place the catheter over a central guide wire 17A placed first through the mouth and esophagus into the stomach with an endoscope. Once the catheter is in position determined by distance graduations (not shown), the balloon can be inflated to help deploy the GARD™ ring as shown in Fig 5A. Once the balloon has been inflated, the three arms of the balloon expander 22 will be lifted and will push up the distal end of the guiding tubes so that the injection catheter 19 placed in the guiding tube 18 can be pushed until the injection catheter makes contact with the wall of the esophagus 10 at a proper angle. The needle is then deployed and pierces the wall of the esophagus at the depth needed to reach the muscular layer of the esophagus.

[0061] Fig. 5 A illustrates an injection balloon catheter 15 with inflated balloon 16 and guiding tubes 18 for injection. The injection catheter 19 includes needle 20 shown in the wall of the esophagus 1. A syringe 21 with botulinum toxin is shown ready for injection in the wall of the esophagus 1.

[0062] Fig. 5B illustrates a balloon expander 22 with 3 arms spread.

[0063] In Figs. 6 and 7, a variant is shown, a triangular balloon 23 not yet inflated in Fig. 6 is inflated in Fig. 7 and pushes up the arm 22 of the balloon expander and the end of the guiding tube 18 at a proper angle so that the injection catheter 19 will reach the esophageal wall and the needle 20 will penetrate the esophageal wall at the desired depth reaching the esophageal wall of the esophagus.

[0064] Fig. 8A illustrates a combination of the delivery catheter or GARD™ Introducer with the Botulinum toxin injection catheter wherein the GARD™ ring 3A is folded during insertion and held in place with a suture 25A around the ring 3A to keep the ring folded and a knot 24A and thread 25A that then penetrates in the central catheter 17 through port 17C which is the proximal exit of the thread 25A. In a similar way, the GARD™ tube 4 is also folded and held in place with a suture (not shown in the bottom of the drawing) and a knot (not shown in the bottom) that will be pulled out when pulling on 25B at the top of the drawing to the left. A security thread (not shown in the bottom of the drawing) holds both knots secure and is released by pulling on 25C shown on the top of the drawing. The tubular part 4 of the GARD™ can be either smooth or lamellar as shown in Figs. 1A-1B. Fig. 1A shows a smooth tubular part 4A of the GARD device. Fig. IB shows a lamellar tubular part 4B of the GARD™ device. Fig 8A is a combination of the delivery catheter or GARD™ Introducer with the Botulinum toxin injection catheter. In one optional embodiment, the knot 24A used is a special knot known as the “draw hitch” that can be released simply by pulling at one end, even at a distance and the knot will be released and the thread can be pulled out very easily. The security has to be pulled out first before the 2 other knots can be released.

[0065] Fig 8B is a transverse cross-sectional view of the central catheter 17, showing a lumen for the central guide wire 17A, lumen 17B for inflation of balloon and 17D is empty for possible future use, lumens for threads 25A and 25B and security thread 25C for the deployment threads of the GARD™ ring and tube. Guiding tubes 18 for the injection catheter are illustrated. Fig. 8C is a variant of Fig 8B with a fourth “bean shape” hole, 2 holes 17C and 17E are used for the threads 25A and 25B used to deploy the ring and tube of the GARD™ device and a security thread 25C passing through 17E. 17B is for inflation/deflation of the oval balloon and 17D is a spare lumen that can be used if needed for inflation of the triangular balloon, see Fig 11 , when and if 2 balloons are used.

[0066] Fig. 9 shows threads 25A, B, and C pulled out to release the GARD™ and air injection 17B to inflate the balloon, shown inflated. In Fig. 9, the three knots are released, first the security knot 25C then 25 A and 25B, and the GARD™ ring expands as well as the tube. The balloon is then inflated 17B to make sure that the GARD™ ring expands properly and reaches the wall of the esophagus. A gastroscope or fluoroscopy or both can be used optionally to check that the GARD™ ring is properly expanded. [0067] Fig. 10 illustrates threads 25 A, B, and C completely pulled out of the catheter with balloon 16 inflated and injection catheter 19 in guiding tube 18 with needle 20 drawn to penetrate the esophageal wall muscular layer 9. Syringe 26 pumps toxin so it is injected through needle 20. This operation is repeated three times in each of the 3 guiding tubes then the catheter can be rotated and the same operation can be repeated once or twice depending on the diameter of the esophagus so that 6 infections (for smaller diameter GARDs™ with a small circumference of the ring) up to 9 injections of botulinum toxin (for larger diameter GARDs with a larger circumference of the ring) can be performed at the exact depth in the muscular layer of the esophagus and at equidistance around the circumference of the esophagus above the deployed GARD™ ring.

[0068] Fig 11 illustrates a combination of a top small triangular, or conical balloon 23 used to spread the arms of the arm expander 22 and the guiding tube 18 and a bottom oval balloon 16 to help deploy the ring of the GARD™. A stopper 30 in the middle of both balloons separates both balloon and prevents the folded ring (not shown folded) to move upwards when the threads are pulled out (see Fig 10) during deployment of the ring 3A. The distance between the injection needle and the upper limit of the ring of the GARD™ should be in the order of 1 cm to 2 cm, preferably 1 cm so the botulinum toxin acts at its best to prevent migration of the GARD™ ring. If necessary, the oval balloon can be deflated once the GARD™ ring is deployed and the device pushed down a few centimeters so that the small triangular or rather conical balloon is right above the ring 3 A (not shown) and the injection of botulinum are even closer to the top part of the GARD™ ring.

[0069] Fig. 12A is a side perspective view of an alternative GARD Introducer with a Botulinum toxin injection catheter and with a guide wire (see Figs. 12B and 12C) according to the presently disclosed technology.

[0070] The catheter 17 of the present embodiment can include a plurality of, and optionally three, vertically spaced-apart and vertically and/or linearly aligned openings 30A, 30B, 30C extending through a sidewall thereof in a body of the catheter 17. The openings 30A, 30B, 30C are optionally aligned to be parallel to the longitudinal axis L of the catheter 17 and each other. Each opening 30A, 30B, 30C being sized, shaped, and/or configured to allow a thread to pass therethrough.

[0071] In one embodiment, an upper end of the catheter 17 can optionally include a proximal opening 36 leading to a central passageway of the catheter 17. The sidewall can surround the central passageway. The proximal opening 36 and the central passageway are optionally in vertical alignment with the longitudinal axis L of the catheter 17. The guide wire 17A can extend through the proximal opening 36 and the central passageway and can run parallel with the longitudinal axis of the catheter 17 when the guide wire 17A extends through the catheter 17. In addition, the catheter 17 can include a port 34 offset from or extending at an angle (e.g., at approximately 20-30 degrees) from the longitudinal axis L of the catheter 17 and spaced-apart from the opening 36. The port 34 can surround a relatively short passageway that leads to the central passageway. The port 34 can be sized, shaped, and/or configured to receive each of at least three threads 31A, 31B, 31C therein. In one option embodiment, each of the threads 31A, 31B, 31C can enter into the catheter 17 at the port 34, and exit the catheter 17 at one of the openings 30A, 30B, 30C.

[0072] As shown in Fig. 12A, the first thread 31 A can exit the catheter 17 at the lowest most opening 30A, the second thread 31B can exit the catheter 17 at the middle opening 30B, and the third thread can exit the catheter 17 at the upper most opening 30C. The first thread 31 A can optionally be a security thread or a back-up thread, and can be omitted if desired. The second thread 3 IB can be configured for holding the ring 3A. The third thread 31C can be configured for holding the tube 4. The threads are not limited to being formed of a particular material, or being a particular size. The threads can be formed of the same material, or different threads can be formed of different material.

[0073] Optionally, the presently disclosed technology can include at least two draw string knots 31D, 31E. In particular, a free or straight end of the first thread 31A can extend through a first one of the draw string knots 31 D, which can be attached to the ring 3 A. A second one of the draw string knots 31E can be attached to the tube 4.

[0074] In one optional embodiment, as shown in Fig. 12A, the proximal end of the catheter is divided, such that the guide wire 17A extends generally or exactly straight along the longitudinal axis L and the threads 31 A, 3 IB, 31C extend out on one side of the catheter. The upper part of the catheter shown in Fig. 12A is the proximal part of the catheter that is out of the body, which the endoscopist and/or his/her assistant(s) have access to work on.

[0075] Figs. 1A and IB show the position of the GARD™ device in the lower esophagus 1. Once the delivery catheter with the folded device is in position in the esophagus held by the threads, first a first thread 31 A can be pulled out completely from the catheter 17. Next, a second thread 31B holding the top 3C of the ring 3A with the helical spring 3B within a silicon ring will be freed by pulling on it. The ring 3 A will deploy to reach the wall of the esophagus. Then, the tube 4B is freed by pulling on a third thread 31C. Thus, the device is deployed and the catheter is removed after the threads have been completely pulled out. The present embodiment does not employ or require a balloon or any guiding tubes (e.g., compare Figs. 8B and 8C to Figs. 12B and 12C).

[0076] In operation of one optional embodiment, the guide wire 17A is first placed at the endoscopy with the gastroscope through a standard working channel of the gastroscope. Then, the gastroscope is removed and the delivery catheter is placed on the guide wire into the esophagus. The gastroscope is replaced in the esophagus to determine where to place the ring 3A and pull on the plurality of threads to deploy the ring 3A and place the ring in in the desired position in the esophagus.

[0077] Fig. 12B is a cross-sectional view of the central catheter of Fig. 12A.

[0078] Fig. 12C is an alternative cross-sectional view of the central catheter of Fig. 12A.

[0079] Fig. 13 is a side perspective view of the alternative GARD Introducer of Fig. 12A with threads untied.

[0080] Fig. 14 is a side perspective view of the alternative GARD™ Introducer of Fig. 12A without the threads and/or after the thread have been pulled out or removed from the catheter 17. The tubular part 4 of the GARD™ can be either smooth or lamellar as shown in Figs. 1 A-1B. Fig. 1A shows a smooth tubular part 4A of the GARD™ device. Fig. 2A shows a lamellar tubular part 4B of the GARD device.

[0081] Botulinum toxin is a neurotoxic protein produced by the bacterium Clostridium botulinum and related species. It prevents the release of the neurotransmitter acetylcholine from axon endings at the neuromuscular junction and thus causes flaccid paralysis of the muscles. Botulinum toxin also paralyzes smooth muscles as well as striated muscles.

[0082] Botulinum toxin, particularly type A, is already widely used in medicine and sold as BoTox® by Allergan, Dysport® by Ipsen Pharma and Xeomin® by Merz Pharmaceuticals for treatment of muscular blockage in the eye for blepharospasm, bladder hyperactivity, cervical dystonia, chronic migraine, focal limb spasticity, and for face wrinkles.

[0083] According to the invention botulinum toxin can be injected in very small volumes, in the order of 0.1 ml to 0.4 ml, which is desirable for injection in a very narrow area of esophageal muscle about 1 mm to 2 mm thick (about 0.04 to 0.08 inches).

[0084] To avoid injecting potentially toxic botulinum toxin through the wall of the esophagus, an injection device incorporated or clipped on the delivery system used to place the GARD in the esophagus or an independent injection device from the catheter used to place the GARD in the esophagus is used to inject the botulinum toxin around the inner circumference of the esophagus at a precise depth in the wall of the esophagus.

[0085] In some embodiments, the injection device can include a balloon that is inflated when in position with three “guiding” tubes placed at 120 degrees of each other around the 360 degree circumference. Once inflated, when the balloon is in contact with the wall of the esophagus, the exact angle of the guiding tube and the wall of the esophagus can be determined precisely as the end portion of the guiding tubes is glued to the top part of an hexagonal shaped balloon or better placed on an “balloon expander” made of a ring and 3 “legs” that are spread by the inflated balloon. An injection catheter obtained commercially (Olympus Needlemaster™ needles, Boston Scientific Interject™ , Cook Medical AcuJect™) is passed through the guiding tubes until the catheter reaches the esophageal wall. Since the angle between the catheter with the needle and the wall of the esophagus depends on the diameter of the esophagus that conditions the volume of air used to inflate the balloon and the diameter of the ring of the GARD™ device used for a given patient, the exact depth of injection can be calculated for each diameter of GARD™ ring and the appropriate catheter with needle length, normally between 3 mm and 6 mm long can be chosen in advance so as to inject at a 2 mm depth in the muscular layer of the esophagus in order to inject the botulinum toxin blindly through the esophageal wall into the muscular layer of the esophagus, avoiding injections in the mucosa or submucosa that is too proximally which can cause esophageal mucosal lesions or too deep through the wall of the esophagus that can lead to mediastinitis with cases of deaths reported (see Complications of botulinum toxin injections for treatment of esophageal motility disorders, van Hoeij FB, et al., Dis Esophagus 2017 Feb 1 ; 30(3): 1-5). Also, using fluoroscopy can help assess the good position of the injection catheter and the depth of the needle in the wall of the esophagus.

[0086] The regular disposition every 120 degrees of the guiding tubes allows injections at 3 equidistant locations around the circumference of the esophagus. The balloon is then deflated, the catheter turned 40 degrees and then reinflated with 3 more injections. In larger size diameters of the GARD™ ring as in 30 mm, the operation is repeated a third time as the circumference of the esophagus will be approximately 90 mm so 9 injections of 10 units of botulinum toxin for a total of 90 Units is used, while in a smaller 20 mm diameter of GARD™, a 60 degree rotation once with 6 injections is sufficient as the circumference is about 60 mm and 6 injections of 10 to 15 units of botulinum toxin is sufficient.

[0087] In some embodiments, the device does not include a balloon. In further embodiments, an endoscopic injection needle is passed through the endoscope. In some embodiments, the needle is used for 4-12 injections. In further embodiments, an injection is made right above the ring of the GARD™.

[0088] Botulinum toxin injection into the gastroesophageal junction of the esophagus is used for more than 20 years to treat patients who have achalasia and non-cardiac chest pain with non-reflux, nonachalasia spastic esophageal motor disorders and studies have demonstrated efficacy in relieving pain see “Botulinum toxin for achalasia” by Pasricha et al in the Lancet 341 :244-245, 1993 and “Treatment of chest pain in patients with noncardiac, nonreflux, nonachalasia spastic esophageal motor disorders using botulinum toxin injection into the gastroesophageal junction by Larry S Miller et al. in the American Journal of Gastroenterology 97,1640-1646 (2002)). [0089] As Botulinum toxin is a potential toxic compound, the use of an injection guide to help the endoscopist inject the botulinum toxin at the selected, right location and at a selected depth to reach the muscular layer of the esophagus mitigates the potential risks of botulinum toxin injections.

[0090] Also, it is known that botulinum toxin injection will last for up to one year which is more than sufficient for the first generation DM-GARD™ that will be used up to 4 weeks then replaced after 1 month by the Therapeutic-GARD™ and Obesity-GARD™ that will include features in addition to the botulinum toxin to help keep the devices in place for longer periods of time.

[0091] EP 2729162 Bl assigned to Allergan, Inc. describes treating two conditions, Diffuse Esophageal Spasm (DES) and “Nutcracker esophagus,” with Botox A injections in the esophagus. [0092] The presently disclosed technology can include injecting Botulinum toxin A in the muscular layer of the body of the esophagus right above the ring of the GARD™, not all along the length of the esophagus as needed for DES and Nutcracker which the procedure described in the Allergan patent. Allergan’s patent does not describe using Botox A to prevent migration of a medical device like the GARD.

[0093] Botulinum toxin A will not be used for injections in the esogastric junction as used in achalasia but exclusively in association with medical devices to diagnose and treat GERD, LPR and obesity above the esogastric junction in the lower third of the esophagus and preferably about 3 cm to 5 cm above the Z line which is the limit of the gastric mucosa and the esophageal mucosa at the esogastric junction.

[0094] The balloon element of the system has two functions, first to help deploy the GARD™ ring and stabilize the guiding tubes thanks to the balloon expander before botulinum toxin injection and second to enable exact placement of the delivery catheter with the balloon in the center of the esophagus which in turn enables appropriate placement of the guiding tubes in the correct direction and right angle to control depth of botulinum toxin injection precisely into the muscular layer of the esophagus that is 2 mm deep while operating at a distance of about 1 meter (or about 3 feet) away. The injection is made about 1 cm above the upper ring of the GARD™ with a purging volume in the catheter of approximately one milliliter and a controlled length of the needle of 3 mm to 6 mm when taken out of the protection sheath at endoscopy using a 21 to 25 gauge needle, preferably a 23 gauge needle, that will reach both smooth muscle layers of the esophagus to avoid injecting the toxin at another location either too proximally in the mucosa or submucosa of the esophagus or too distally beyond the esophagus as the botulinum toxin can be very toxic even at very low dose.

[0095] In some embodiments, the system does not include any guiding tubes. An endoscopic injection needle is passed through the endoscope.

[0096] Referring to Figs. 15A-17C, the presently disclosed technology can employ an inflatable calibration balloon 38. In one optional embodiment, the calibration balloon 38 can have a diameter in an inflated configuration of about 3 mm. The balloon 38 can be employed to calibrate the esophagus 1 of the patient and/or expand the ring of the GARD™ when it does not expand as desired.

[0097] In one optional embodiment, when a healthcare professional carefully calibrates the esophagus 1 by placing the deflated calibration balloon 38 in the esophagus 1 at the location of the GARD™ implantation and inflates the calibration balloon 38 with air (optionally via syringe 21) until it is impossible to inflate the calibration balloon 38 more and the calibration balloon 38 is completely distending the esophagus 1 as observed with the gastroscope, the volume of air used for the distension is noted. Then, the calibration balloon 38 can be deflated and taken out of esophagus 1 of the patient. The calibration balloon 38 can then be reinflated outside the patient with the same volume of air used to inflate the calibration balloon 38 in the esophagus 1. The diameter of the calibration balloon 38 can then be measured by a calibration card or calibration block 40 (see Fig 16), which in one optional embodiment measures two centimeters high with ten holes measuring precisely between 21 mm and 30 mm in diameter. The calibration balloon 38 can then be reinflated and the exact diameter is measured. If the inflated calibration balloon 38 is between two holes sizes, the larger hole size is measured.

[0098] The above-described method of esophageal measurement and therefore of GARD™ measurement guarantees that the ring of the GARD™ is always on the “high” diameter size. Once introduced in the esophagus 1 and released by pulling the threads, thereby liberating the slip knots and the ring as well as the rest of the GARD™ (DM1 , DM2 or DM3) deploys, chose the larger size if the measurement is between 2 sizes, the healthcare professional can then place a DM-GARD™ that is about 0 mm to 1 mm larger than the actual reality of the esophagus 1 diameter because of the method described above and once released, the ring does not deploy completely, which is good for keeping the device in place for up to about 3 months, typically.

[0099] To help deploy the ring of the DM-GARD, the healthcare professional can use the calibration balloon 38 in the stent and inflate the calibration balloon 38 to help distend the folded ring against the wall of the esophagus 1 or do maneuvers with the tip of the endoscope to push the ring of the DM 1 against the wall of the esophagus 1.

[0100] Even when a healthcare professional uses all of the above-described methods, the ring does not always distend completely and there can often be the help of the host’s body heat that makes the ring softer and helps distend the ring against the wall of the esophagus 1, the DM1 tends to fall into the stomach most of the time before 4 months of implantation.

[0101] In another optional method of the presently disclosed technology, the GARD device can be placed in the esophagus with a top nitinol helicoidial spring ring folded on the delivery catheter and held in position without a balloon. In such an embodiment, the catheter can be placed in the esophagus with the help of a guide wire catheter held in position for introduction, and the threads can be pulled out and the ring GARD can be deployed spontaneously due to the helicoidal spring in the ring.

[0102] To inject botulinum toxin, three catheters are not necessary, but simply inject the botulinum toxin with a needle placed through the instrument channel and the mucosa is injected with boutinun toxin all around the upper circumference of the GARD ring.

[0103] In one optional embodiment, as shown in Fig. 15C, a manometer 39 or other pressure measurement device can be employed to indicate to the user how much air was injected into the calibration balloon 38 when the balloon 38 is in the esophagus. The same procedure can be repeated once the calibration balloon 38 is outside of the body or esophagus to determine the diameter of the ring of the esophagus to be chosen and therefore the size of the GARD device. The manometer 39 can be attached in any of a variety of ways, such as with a luer-lock connection.

EXAMPLES

[0104] As an example, a total volume of 1 ml of solvent will be used in a 100-Unit vial of Botox or Xeomin so that each 0.1 ml of solution contains 10 Units of botulinum toxin. Once the catheter is purged with the solution outside the body of the patient, there should be at least 1 ml of the botulinum toxin ready for injection in the syringe after purging the catheter with the botulinum solution. At about 1 cm above the ring, 0.1 ml to 0.15 ml corresponding to 10U to 15U should be injected at 6 to 9 sites of equal distance around the circumference of the esophagus for a total of about 90 units of botulinum toxin. To help the endoscopist proceed with the injection, a catheter with 3 injection tubes will help guide the injection catheter at a pre-determined angle of penetration of the esophageal wall depending on the inflation of the balloon, which will help determine the depth of injection. Also, the use of fluoroscopy can help guarantee injection in the esophageal wall and in the proper muscular layer of the esophageal wall. The preferred botulinum toxin for injection used is Xeomin® by Merz where 1 ml of NaCl 0.9% is used to reconstitute the solution then injected in an Olympus endoscopic injection catheter. However, other brands of botulinum toxins can be used as well as other catheter and dosages.

[0105] In an example, the system does not include a balloon. An endoscopic injection needle is passed through the endoscope. The needle is used for a number of injections, such as 4-12 injections. An injection is made right above the ring of the GARD™, for example about 1 cm above. In some embodiments, the needle is used for 4-12 injections. In further embodiments, an injection is made right above the ring of the GARD.

[0106] The following exemplary embodiments further describe optional aspects of the presently disclosed technology and are part of this Detailed Description. These exemplary embodiments are set forth in a format substantially akin to claims, although they are not technically claims of the present application. The following exemplary embodiments refer to each other in dependent relationships as “embodiments” instead of “claims”.

[0107] 1 A. A system comprising a catheter device configured to orient an injection and configured to allow injection of botulinum toxin at a selected depth in the esophagus of a patient to reach the muscular layer around the circumference of the esophagus to block peristalsis, the system not including a balloon.

[0108] IB. The system of embodiment 1 A, wherein the system does not include one or more guiding tubes.

[0109] 1C. The system of embodiment 1 A, wherein the catheter device is configured to reach the esophageal wall at a predetermined angle and the botulinum toxin injection is injected in the muscular layer of the esophagus.

[0110] ID. The system of embodiment 1 A, further comprising a gastroesophageal anti-reflux device having a ring maintained in a folded state with a thread tied with a draw string knot, the draw string knot being adapted to be untied by pulling on a string, thereby allowing the ring to unfold.

[0111] IE. The system of embodiment ID, wherein the ring is configured to unfold to reach the wall of the esophagus.

[0112] IF. The system of embodiment ID, wherein the size of the ring is calibrated to the size and location of the esophagus.

[0113] 1G. The system of claim embodiment IF, wherein the catheter device is configured to reach the esophageal wall at a predetermined angle and the botulinum toxin injection is injected in the muscular layer of the esophagus.

[0114] IE. The system of embodiment 1A, wherein the catheter device includes an opening spaced apart from a port at a proximal end thereof and a plurality of spaced-apart openings in a body thereof.

[0115] IF. The system of embodiment IE, wherein threads are configured to enter the catheter at the port and exit the catheter at one of the plurality of spaced-apart openings, each thread being configured to be removably attached to the gastroesophageal anti-reflux device. [0116] 1G. The system of embodiment 1A, wherein the catheter includes three vertically spacedapart openings extending through a sidewall thereof, each opening being configured to allow a thread to pass therethrough.

[0117] The presently disclosed technology, therefore, is well adapted to carry out the objectives and attain the ends and advantages mentioned, as well as others inherent therein. While the presently disclosed technology has been depicted and described and is defined by reference to particular embodiments of the invention, such references do not imply a limitation, and no such limitation is to be inferred. Consequently, the presently disclosed technology is intended to be limited only by the spirit and scope of the appended claims, giving full cognizance to equivalents in all respects.

Claims

CLAIMS What is claimed is:

1. A system configured to prevent contraction or peristaltic wave action of an esophagus of a patient causing displacement of a gastroesophageal anti-reflux device having a ring used to diagnose and manage refractory Gastroesophageal Reflux Disease (GERD) from an intended location in the esophagus towards or into the stomach, the system comprising: a catheter including: an opening at a proximal end thereof; a port spaced-apart from the opening and located near a proximal end of the catheter; and a plurality of spaced-apart openings in a body thereof; and threads configured to enter the catheter at the port and exit the catheter at one of the plurality of spaced-apart openings, each thread being configured to be removably attached to the gastroesophageal anti-reflux device.

2. The system of claim 1 , wherein botulinum toxin is injected in the esophagus to reach the muscular layer around the circumference of the esophagus to block peristalsis.

3. The system of claim 1 , wherein the catheter is configured to reach the esophageal wall at a predetermined angle.

4. The system of claim 1 , wherein a calibration balloon is employed to measure the interior of the esophagus of the patient.

5. The system of claim 4, wherein the calibration balloon is configured to be inflated within the esophagus such that the volume of air injected into the calibration balloon can be measured, the calibration balloon being configured to be deflated and removed from the esophagus, the calibration balloon being configured to be reinflated outside of the patient and a size of the calibration balloon being compared to a calibration card.

6. A method of preventing contraction and peristaltic wave action of an esophagus causing displacement of a medical device from an intended location towards or into the stomach, the method comprising: injecting botulinum toxin in the wall of the esophagus at the level where the medical device will be placed, wherein the method does not employ a balloon.

7. The method of claim 6, wherein the method does not employ a guiding tube.

8. The method of claim 7, wherein the medical device includes a gastroesophageal antireflux device having a ring maintained in a folded state with a thread tied with a draw string knot.

9. The method of claim 8, further comprising untying the draw string knot by pulling on a string, thereby allowing the ring to unfold.

10. The method of claim 9, wherein the medical device includes a gastroesophageal antireflux device having a ring and a tube.

11. The method of claim 6, further comprising: pulling a first thread through a catheter; pulling a second thread through a catheter thereby disengaging the second thread from the ring; and pulling a third thread through the catheter thereby disengaging the third thread from the tube.

12. The method of claim 11, wherein the catheter includes an opening at a proximal end thereof, a port spaced- apart form the opening and at or near a proximal end thereof, and a plurality of spaced-apart openings in a body thereof.

13. The method of claim 12, wherein the plurality of spaced-apart openings are vertically or linearly aligned.

14. A system comprising: a catheter including: an opening at a proximal end thereof; a port spaced-apart from the opening and located at or near a proximal end of the catheter; and a plurality of spaced-apart openings in a body thereof, wherein the catheter is configured to receive threads that enter the catheter at the port and exit the catheter at one of the plurality of spaced-apart openings.

15. The system of claim 14, wherein the system is configured to prevent contraction or peristaltic wave action of an esophagus of a patient, the contraction or peristaltic wave action causing displacement of a gastroesophageal anti-reflux device having a ring used to diagnose and manage refractory Gastroesophageal Reflux Disease (GERD) from an intended location in the esophagus towards or into the stomach.

16. The system of claim 15, wherein each thread is configured to be removably attached to the gastroesophageal anti-reflux device.

17. The system of claim 15, wherein the catheter is configured to reach the esophageal wall at a predetermined angle.

18. The system of claim 15, wherein a calibration balloon is employed to measure the interior of the esophagus of the patient.

19. The system of claim 18, wherein the calibration balloon is configured to be inflated within the esophagus such that the volume of air injected into the calibration balloon can be measured, the calibration balloon being configured to be deflated and removed from the esophagus, the calibration balloon being configured to be reinflated outside of the patient and a size of the calibration balloon being compared to a calibration card.

20. The system of claim 14, wherein the plurality of spaced apart openings are linearly aligned and extend through a sidewall of a body of the catheter.