Abstract:
Devices and methods for surgically altering stomach tissue to change gastric emptying. Plications are formed in the stomach speed up or slow down gastric emptying, depending on the number and locations of plications used. The plications may be formed endolumenally.

Description:
REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application is a Continuation-in-Part of U.S. patent application Ser. No. 12/409,335 filed on Mar. 23, 2009, and now pending, which claims priority to U.S. Patent Application No. 61/038,487 filed on Mar. 21, 2008. 
         [0002]    This Application is also a Continuation-in-Part of U.S. patent application Ser. No. 11/070,863 filed on Mar. 1, 2005 and now pending, which claims priority to U.S. patent application Ser. No. 10/840,950 filed on May 7, 2004 and now pending. 
         [0003]    This Application is also a Continuation-in-Part of U.S. patent application Ser. No. 10/735,036 filed on Dec. 12, 2003 now pending, which is a Continuation-in-Part of U.S. patent application Ser. No. 10,639,162, filed Aug. 11, 2003, now U.S. Pat. No. 7,618,426. Each of the Applications listed above is incorporated herein by reference. 
     
    
     BACKGROUND OF THE INVENTION 
       [0004]    The stomach is a muscular hollow part of the human alimentary system, and it plays a vital role in the digestive process. It serves many purposes, including the role of reservoir for food, a role in chemical and mechanical grinding/digesting of food, and as a precursor and catalyst for a wide variety of chemical and hormonal changes before, during and after a meal. The stomach has distinct anatomical regions generally know as the fundus, corpus, (body) gastric antrum and pylorus. The stomach has a sphincter muscle at both ends which serves to manage the passage of nutrients during eating and digestion. 
         [0005]    The stomach is surrounded by parasympathetic (stimulant) and orthosympathetic (inhibitor) plexuses, which are networks of blood vessels and nerves in the anterior gastric, posterior, superior and inferior, celiac and myenteric sections of the stomach. These regulate both the secretions activity and the motor (motion) activity of stomach muscles. 
         [0006]    Stomach functions are controlled by both the autonomic nervous system and by the various digestive system hormones. As a reservoir, the fundus and to a lesser extent, the antrum, serve to dilate during ingestion of a meal, providing the space for short-term accommodation of the food to be digested, and for partially digested food. 
         [0007]    The stomach has various states of activity, corresponding to pre-, intra- and post-meal functions. At the ingestion of a meal, the proximal stomach relaxes, creating a space for meal storage. The stomach begins the movement of food to the antrum, where it is mixed with digestive chemicals and is ground into chyme by muscular contractions. Once the antrum has milled the food, the pylorus opens reflexively, permitting passage to the duodenum. This partially-digested material is then passed through the pylorus and into the small bowel where further digestion and the absorption of nutrients takes place. In healthy humans, the amount of time it takes for the stomach to completely empty (gastric emptying time) is regulated very carefully to match the capacity of the duodenum to take on material and the body&#39;s ability to digest the nutrients. 
         [0008]    Using a variety of methods, this “gastric emptying” time can be measured and used to determine if a patient has normal or abnormal characteristics. In normal patients, the presence of food in the stomach and later, in the small bowel, sets off a wide range of chemical responses that tell the brain when to eat, how much to eat, and when to stop eating. Further, scientist and clinicians are discovering that the presence and passage of nutrients through the alimentary system triggers a number of chemical processes that effect eating behavior, digestion, blood sugar, the autonomic nervous system, and the immune system. A “brain gut” link has been described in the literature and is the focus on a great deal of current research, especially as it relates to obesity, diabetes, hyperlipidemia, cardiovascular risk profile and dementia. 
         [0009]    One area of intensive medical research focuses on the relationship between gastric emptying time and disease. It has been discovered that disordered gastric emptying (either too fast or too slow) is prevalent in patients with both Type 1 and Type 2 diabetes, and problems associated with gastric emptying result from and contribute to the symptoms and morbidities associated with the disease. In some patients, particularly those with recently-diagnosed type 2 diabetes, emptying may be accelerated, leading to a variety of serious clinical problems, and in others it is delayed, also leading to a variety of serious clinical problems. Problems include pain, nausea, vomiting, hypo- and hyper-glycemia, dumping syndrome, hyperlipidemia and hypertension. Current treatments are lacking and have significant limitations and side effects, and the prognosis of patients with disordered gastric emptying is poor. 
         [0010]    Many patients with longstanding diabetes mellitus suffer from a condition known as gastroparesis, or severely delayed gastric emptying. Although diabetes is thought to be the cause, there are many patients with gastroparesis of unknown origin. In total, up to 75% of diabetic patients suffer from some degree of gastroparesis. Gastroparesis results from and also contributes to poor glycemic control thereby creating a cycle that increases the morbidity associated with diabetes. Patients with delayed gastric emptying could benefit from interventions that increase gastric emptying speed. Similarly, patients that suffer from accelerated emptying could benefit from therapeutic interventions that slow down gastric emptying. In either case, beyond just alleviating the immediate physical symptoms of disordered gastric emptying, therapeutic modulation of emptying can improve glycemic control and increase insulin sensitivity, thereby lessening the problems associated with diabetes. In some studies, when gastric emptying is normalized, insulin requirements post-meal have been shown to lessen. 
         [0011]    There is a strong relationship between gastric emptying time and appetite, as well as emptying time and food intake. Gastric distension from the swallowed food, as well as nutrient stimulation of alimentary tract receptors and the release of gut peptides have a strong influence on meal size (satiation) and the amount of time before hunger returns (satiety). The effect of gastric emptying speed on obesity is just now being understood, but it is clear that the rate of gastric emptying can have an effect on a patient&#39;s body weight. Some researchers have proposed that speeding up gastric emptying time can trigger earlier responses to a meal, thus lessening food intake, while others propose that delaying or prolonging the total emptying time of a meal might reduce hunger between meals. 
         [0012]    The mechanisms of action of these effects are not completely understood, but a leading hypothesis is that the rapid entry of partially-digested nutrients into the distal gut causes the release of GLP-1 (glucagon-like peptide 1) and peptide YY, both of which have a role in appetite and energy intake. Further, prolonging total emptying time may enhance this effect by prolonging the release of these peptides, while delaying the elevation of ghrelin and other triggers of hunger and eating behavior. 
       SUMMARY OF THE INVENTION 
       [0013]    Interventions that normalize gastric emptying can alleviate symptoms and provide a treatment for diabetes, both Type 1 and Type 2, and other conditions. For treatment of patients with accelerated gastric emptying, plications can be used in a variety of ways to slow gastric emptying. Plication of the corpus and/or antrum may create a valve or other obstacle to the rapid passage of food (i.e. speed bump). Plication of the corpus and/or antrum may be used to make normal motor function (peristalsis) inefficient or slower, thus slowing the propulsion of food to the small bowel. Plicating the pylorus may be used to tighten this valve and/or limit its opening diameter, thus slowing the passage of food. 
         [0014]    Slowing gastric emptying by surgery of the stomach may provide an effective treatment for disorders associated with accelerated gastric emptying. By slowing emptying, release of gut hormones may be delayed, thereby prolonging satiety. This can cause weight loss by lengthening the time between meals. Surgically slowing emptying can provide a treatment for postparandial hypotension dumping syndrome. It may also improve glycemic control, providing a treatment for diabetes or its symptoms. 
         [0015]    As a treatment for delayed gastric emptying and/or gastroparesis, plications can be used to accelerate emptying. Plication of the fundus may limit the stomach&#39;s function as a reservoir of food, or shrink its volume, thus forcing food to move to the distal stomach faster. Plicating the fundus and/or the corpus may prevent storage of food in the proximal stomach and thereby speed its delivery to the antrum. It may also propel food faster in to the duodenum. 
         [0016]    Surgery of the stomach that speeds up gastric emptying may be a treatment for disorders associated with delayed gastric emptying, or gastroparesis. By speeding emptying, the symptoms of gastroparesis, including nausea, vomiting and pain, may be reduced. Surgically speeding emptying may also initiate gut hormone response earlier, thus triggering fullness faster and limiting meal size. It may also increase the level of certain gut hormones that optimize/improve glycemic control, thereby treating some of the symptoms of diabetes. 
         [0017]    By speeding emptying, the level of certain gut hormones that improve insulin resistance may be increased, thereby treating diabetes. Limiting time that food stays in the stomach may reduce the stomach&#39;s ability to contribute to the digestive process, thereby moving undigested or partially digested nutrients into the distal gut. This can trigger the metabolic benefits of a gastric bypass without intestinal reconfiguration. It has been shown that gastric bypass has metabolic effects that precede the weight loss normally associated with the procedure. 
         [0018]    Plicating the stomach may speed the emptying of some of the nutrients into the small bowel, and prolong the total emptying cycle at the same time. In combination, this could provide a treatment for obesity and diabetes. Plicating the fundus and/or body and/or antrum and/or pylorus may speed the arrival of nutrients to the small bowel. Plicating these same areas may make the digestions process inefficient, therefore making total emptying time longer. 
         [0019]    Early release of gut hormones may limit meal size and thus caloric intake, while the presence of food in the antrum for longer periods (longer total emptying time) may delay the release of hormones that promote hunger, therefore lengthening the time between meals. Modulating and prolonging gastric emptying may reverse the negative cycle of glucose insensitivity associated with diabetes, reduce its symptoms, and or lessen the disease itself. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0020]      FIG. 1  is an illustration of an endolumenal system advanced endolumenally into a stomach. 
           [0021]      FIG. 2  is an exploded view of the tissue manipulation assembly and the tissue anchor assembly delivery device shown in the system of  FIG. 1 . 
           [0022]      FIG. 3  is an exploded view of a tissue anchor assembly delivery device shown in  FIG. 2 . 
           [0023]      FIGS. 4A through 4C  are enlarged side views of the tissue manipulation assembly and helical tissue engagement instrument of the system shown in  FIG. 1 . 
           [0024]      FIG. 5  is a schematic representation of a tissue anchor assembly included in the tissue anchor assembly delivery device shown in  FIG. 3 . 
           [0025]      FIG. 6  is a schematic representation of the tissue anchor assembly of  FIG. 5  securing a tissue fold. 
       
    
    
     DETAILED DESCRIPTION 
       [0026]    The anatomy of the stomach can be divided into different segments on the basis of the mucosal cell types and/or in relation to external anatomical boundaries. As shown in  FIG. 1 , the cardiac segment C is immediately subjacent to the gastroesophageal junction (GEJ) and is a transition zone of the esophageal squamous epithelium into the gastric mucosa. The fundus F is the portion of the stomach that extends above the gastroesophageal junction. The body B or corpus of the stomach extends from the fundus F to the incisura angularis on the lesser curvature of the stomach. The majority of parietal acid forming cells are present in this segment. The fundus F and the body B function as the main reservoir of ingested food. The antrum A extends from the lower border of the body B to the pyloric sphincter PS. The majority of gastrin producing or G-cells are present in the antral mucosa. 
         [0027]    The gastrointestinal lumen, including the stomach, includes four tissue layers. The mucosa layer is the top tissue layer followed by connective tissue, the muscularis layer and the serosa layer. When plicating from the peritoneal side of the GI tract, it is easier to gain access to the serosal layer. In endolumenal approaches to surgery, only the mucosa layer is visible via an endoscope. The muscularis and serosal layers are difficult to access because they are only loosely adhered to the mucosal layer. To create a durable tissue fold or plication with suture and anchors, it is preferable to have serosa to serosa contact in the tissue fold. The mucosa and connective tissue layers typically do not heal together in a way that can sustain the tensile loads imposed by normal movement of the stomach wall during ingestion and processing of food. Folding the serosal layers with serosa-to-serosa contact allows the tissue to heal together and form a durable tissue fold, plication, or elongated invagination. 
         [0028]    Turning now to  FIGS. 1 and 2 , an endolumenal system  10  includes an endoscopic body  12  having a covering  22  and a steerable distal portion  24 . The endoscopic body  12  may have at least first and second lumens  26 ,  28 , respectively. Additional lumens may be provided through the endoscopic body  12 , such as a visualization lumen  30 , through which an endoscope may be positioned to provide visualization. Alternatively, an imager such as a CCD imager or optical fibers may be provided in lumen  30  to provide visualization. An optional thin wall sheath may be disposed through the patient&#39;s mouth, esophagus E, and possibly past the gastroesophageal junction GEJ into the stomach S. 
         [0029]    Referring still to  FIGS. 1 and 2 , the endolumenal system includes a tissue manipulation assembly  16  and a tissue anchor deployment assembly  260 . The tissue manipulation assembly  16  includes a flexible catheter or tubular body  12  which is sufficiently flexible for advancement into a body lumen, e.g., transorally, percutaneously, laparoscopically, etc. The tubular body  12  is torqueable through various methods, e.g., utilizing a braided tubular construction, such that when a handle  11  is manipulated and/or rotated by a practitioner from outside the patient&#39;s body, the longitudinal and/or torquing force is transmitted along the body  12  such that the distal end of the body  12  is advanced, withdrawn, or rotated in a corresponding manner. Jaws  18  and  20  are attached to the front end of the body  12 , optionally at a pivot joint connection  19 . 
         [0030]    A launch tube  40  extends through the body  12  may be pivotally attached to the upper jaw. The front end of the launch tube may be designed to change from straight into a curved or arcuate shape when the launch tube is advanced forward. When in the curved shape, the launch tube opening may be generally perpendicular to the upper jaw  20 . The launch tube  40 , or at least the exposed portion of the launch tube  40 , may be fabricated from a highly flexible material or it may be fabricated, e.g., from Nitinol tubing material which is adapted to flex, e.g., via circumferential slots, to permit bending. Movement of the launch tube may also open and close the jaws. Using the launch tube  40  to articulate the jaws eliminates the need for a separate jaw moving mechanism. 
         [0031]    As shown in  FIG. 3 , the tissue anchor assembly delivery system  260  may be deployed through the tissue manipulation assembly  16  by sliding it in through the handle  11  and through the tubular body  12 . Once the needle  272  has been advanced through the tissue fold FF, the first anchor assembly  100  may be deployed or ejected. The anchor assembly  100  is normally positioned within the distal portion of a tubular sheath  264 . Once the anchor assembly  100  has been fully deployed from the sheath  264 , the spent tissue anchor assembly delivery system  260  may be removed and replaced from the tissue manipulation assembly  16  without having to remove the tissue manipulation assembly  16  from the patient. 
         [0032]    The sheath or catheter  264  and the housing  262  may be interconnected via an interlock  270  which may be adapted to allow for the securement as well as the rapid release of the sheath  264  from the housing  262  through any number of fastening methods, e.g., threaded connection, press-fit, releasable pin, etc. 
         [0033]    A pusher  276  which may be a flexible wire or tube within the sheath slides within the housing  262 . An actuator  278  on the housing  262  is used to slide the pusher  276  relative to the sheath  264 , to push anchors out from the opening  274  at the tip of the needle  272 . Needle assembly guides  280  may protrude from the housing  262  for guidance through the locking mechanism. 
         [0034]    As shown in  FIG. 5 , typically, the tissue anchor assemblies include a pair of tissue anchors  50   a  and  50   b , slidably attached to a suture  60 . A knot  62  or other protrusion on the distal end of the suture keeps the distal anchor assembly from sliding off the end of the suture  60 . The suture runs back up through the catheter  264  to the control handle  262 , so that after both anchor assemblies have been deployed, the surgeon can tension the suture. A locking mechanism, such as a cinch  102 , is also slidably retained on the suture  60 . The cinch  102  is configured to provide a cinching force against the anchors to impart a tension force on the suture. With the suture under tension, the proximal anchor assembly  50   b  and the cinch  102  are pushed up against the fold FF. Accordingly, the tissue anchor assembly  100  is adapted to hold a fold of tissue, as shown in  FIG. 6 . 
         [0035]    Surgery on the stomach to speed up or slow down gastric emptying may be performed as follows. The surgical site within the stomach may be visualized through the visualization lumen  30  or a separate imager. In either case, the tissue manipulation assembly  16  and the tissue engagement member  32  may be advanced distally out from the endoscopic body  12  through lumens  26 ,  28 . The distal steerable portion  24  of the endoscopic body  12  is steered to an orientation to position the jaws to engage stomach tissue.  FIG. 1  shows a tissue manipulation assembly  16  advanced through the first lumen  26  and a helical tissue engagement member  32  positioned upon a flexible shaft  34  advanced through the second lumen  28 . To obtain a durable tissue fold FF, the engagement member  32  is advanced or corkscrewed into tissue, as shown in  FIG. 4A . The jaws are opened, optionally by pulling launch tube  40  back as shown in  FIG. 4B . 
         [0036]    The engagement member  32  is then pulled back to draw the engaged tissue FF between the jaws  18  and  20 , as shown in  FIG. 4C . Once the tissue has been pulled or manipulated between the jaws, the jaws are closed, in this case by pushing the launch tube  40  forward. Movement of the launch tube may also change the angle of the jaws and the front end of the launch tube relative to the tissue. 
         [0037]    With the tissue engaged between the jaws  18 ,  20 , a needle assembly may be fed through the handle with the needle  272  moving out of the front end of the launch tube  40 . The needle  272  pierces through the engaged tissue fold FF. The pusher is then used to push out the first anchor. The needle  272  is then pulled back through the tissue fold FF and the second anchor is deployed. The cinch and the second anchor are pushed up against the tissue fold FF, using the jaws or another instrument, to form a permanent tissue fold. Using the methods described above, permanent tissue folds or plications FF may be made in the stomach, to alter gastric emptying. 
         [0038]    Although the methods above are described as endolumenal trans-oral methods, these same methods may be performed in other ways as well, such as trans-anally, percutaneously, laparoscopically, robotically, or even via traditional open body surgery. 
         [0039]    Thus, novel systems and methods have been shown and described. Various changes and substitutions may of course be made without departing from the spirit and scope of the invention. The invention, therefore, should not be limited, except by the following claims and their equivalents.