Systems and methods for duodenal mucosal resection

Abstract

Methods and systems are provided for an endoscopic tissue resection and / or tissue removal device for use with an endoscope. The distal end of the endoscope includes a resection device having one or more elastic bands and a shape memory material anchor associated with each band. After deployment of the band from the distal end of the endoscope, the associated shape memory material provides anchoring into the target mucosal tissue, while the deployed band is positioned to contract.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to U.S. Provisional Application No. 63 / 365,079, filed on May 20, 2022, entitled “SYSTEM AND METHOD FOR DUODENAL MUCOSA RESECTION,” the entire contents of which are incorporated herein by reference. Technical Field

[0003] The present disclosure generally relates to resection of portions of the gastrointestinal tract to treat gastrointestinal diseases. More specifically, the present disclosure relates to devices and methods for resection of portions of the proximal foregut to treat diabetes, obesity, metabolic syndrome, fatty liver, nonalcoholic steatohepatitis (NASH), nonalcoholic fatty liver disease (NAFLD), or polycystic ovarian syndrome (PCOS). Background Art

[0004] Type 2 diabetes mellitus (T2D) is increasing at an alarming rate worldwide, with an estimated global prevalence of 552 million by 2030. According to statistics from the International Diabetes Federation (IDF) in 2017, approximately 425 million people worldwide have diabetes. In the United States, an estimated 30.3 million adults have diabetes, and the number is rising rapidly, with at least 1.5 million new cases of diabetes diagnosed each year. Despite recent advances in medications and technological treatment options, diabetes remains a major public health epidemic. Despite lifestyle interventions and a growing number of medical options, less than half of people with T2D achieve a glycated hemoglobin (HbA1c) level of 53mmol / mol or less. 3 The goal of treatment is to reduce the risk of developing T2D. Bariatric surgery has been shown to be successful in patients with class I, II, and III obesity. In moderately obese patients with T2D, bariatric surgery is superior to intensive medical therapy alone. However, because most bariatric surgical procedures are invasive, irreversible, and associated with some morbidity, bariatric surgery is not a sustainable solution to the growing T2D epidemic.

[0005] As obesity rates increase, non-alcoholic fatty liver disease (NAFLD) has emerged as a major cause of chronic liver disease worldwide over the past few decades. The overall prevalence of NAFLD in adults is estimated to be 23%-25%. Up to 20% of patients with NAFLD are affected by non-alcoholic steatohepatitis (NASH). Despite the increasing prevalence, little is known about the factors that influence the development of NAFLD and the subsequent progression to NASH, liver fibrosis, cirrhosis, and hepatocellular carcinoma. In the vast majority of patients, NAFLD presents in the context of the metabolic syndrome, with insulin resistance being an important pathophysiological mechanism. Currently, liver cancer is the second leading cause of loss of life among all cancers worldwide.

[0006] Polycystic ovary syndrome (PCOS) is a common hormonal disorder in women of childbearing age. PCOS is now recognized as an important metabolic and reproductive disease that leads to a significantly increased risk of type 2 diabetes. Women with the disease have significant insulin resistance, independent of obesity. Obese women with PCOS are insulin resistant. Early diagnosis and treatment, along with weight loss, can reduce the risk of long-term complications such as type 2 diabetes and heart disease.

[0007] The duodenum has been increasingly recognized as a metabolic signaling center that plays a role in regulating insulin action and thus regulating the insulin resistance state. Therefore, the duodenum has become a metabolic therapeutic target, with specific observations of learning and bypassing, excluding or altering duodenal nutrient exposure through bariatric surgery, leading to favorable metabolic changes including immediate improvement in blood glucose regulation after bariatric surgery (which does not appear to be due to malabsorption or the substantial weight loss often observed after surgery). Studies have shown that the small intestine plays an important physiological and pathophysiological role in metabolic homeostasis. Ease of endoscopic access to the duodenum makes it a potential target for disease-modifying interventions for diseases associated with insulin resistance.

[0008] Two main mechanisms are postulated to explain the rapid improvement of T2DM. First, the foregut hypothesis suggests that the improvement in blood glucose after proximal intestinal exclusion is due to a reduction in the secretion of diabetic hormones / anti-incretin factors in response to a lack of nutrients in the proximal small intestine. For example, it is suggested that intestinal glucagon synthesis is reduced after exclusion of the proximal intestine. Secondly, the hindgut hypothesis provides improved blood glucose control to enhance the secretion of incretin-like glucagon peptide-1 (GLP-1) in response to undigested nutrients in the distal small intestine. These theories are not mutually exclusive, and other factors may play a role in the rapid improvement of blood glucose after bariatric surgery. In particular, glucose dependent insulinotropic polypeptide (GIP) may also be involved, and the intestinal hormone stimulates glucagon secretion in response to meals. In addition, caloric intake is of great significance for improving T2DM.

[0009] The duodenum plays an important role in controlling glucose homeostasis through various mechanisms. Some key mechanisms include:

[0010] 1. Enteroendocrine hormone release: The duodenum contains special cells called enteroendocrine cells, which secrete a variety of hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). These hormones are released into the bloodstream when glucose enters the duodenum from the stomach. GLP-1 stimulates insulin secretion from pancreatic beta cells in a glucose-dependent manner. It also inhibits the secretion of glucagon from pancreatic alpha cells, which slows gastric emptying and promotes satiety. GIP also stimulates the release of insulin from pancreatic beta cells in response to increased blood glucose levels. It enhances the absorption and storage of nutrients by promoting the release of insulin and inhibiting the secretion of glucagon.

[0011] 2. Neural signaling: The duodenum is connected to the brain via the vagus nerve, which plays a vital role in regulating glucose homeostasis. Sensory signals from the duodenum (including the presence of glucose) activate vagal afferent neurons, which transmit information to the brain. In turn, the brain sends signals to regulate pancreatic hormone secretion, liver glucose production, and other metabolic processes.

[0012] 3. Incretin effect: The "incretin effect" refers to the enhanced insulin secretion observed when glucose is taken orally compared to intravenous administration. This effect is attributed to the duodenal release of GLP-1 and GIP in response to oral glucose ingestion. These incretin hormones enhance glucose-stimulated insulin secretion, resulting in better clearance of glucose.

[0013] 4. Intestinal gluconeogenesis: The duodenum, along with the jejunum, is able to produce glucose from non-carbohydrate precursors. This process can contribute to glucose homeostasis by providing a source of glucose during fasting or hypoglycemia.

[0014] Overall, the duodenum controls glucose homeostasis through enteroendocrine hormone release, neural signaling, incretin effects, and intestinal gluconeogenesis. Together, these mechanisms regulate pancreatic hormone secretion, insulin sensitivity, and hepatic glucose production, helping to maintain glucose levels within a normal range.

[0015] The duodenum, as the first segment of the small intestine, can influence the development and progression of fatty liver disease through multiple mechanisms. The mechanisms of the relationship between the duodenum and fatty liver are complex and have not yet been fully elucidated. Various factors including genetics, diet, lifestyle, and underlying metabolic status can interact with the duodenal processes mentioned below to influence the development and progression of fatty liver disease. Key mechanisms that explain how the duodenum influences NAFLD or fatty liver disease include:

[0016] Bile acid metabolism: The duodenum is responsible for receiving bile acids from the gallbladder, which are important for the digestion and absorption of dietary fats. Bile acids help emulsify and absorb dietary lipids in the small intestine. Disruption of bile acid metabolism or impaired bile acid flow from the duodenum will contribute to the development of fatty liver disease. Alterations in bile acid composition and availability will affect lipid metabolism in the liver and cause fat accumulation.

[0017] Gut flora: The duodenum and the rest of the small intestine host a diverse community of microorganisms, collectively referred to as the gut microbiota. The gut microbiota plays a key role in various metabolic processes, including lipid metabolism. Disturbances in the composition of the gut microbiota, often referred to as dysbiosis, will affect the metabolism of dietary fat and contribute to the development of fatty liver disease.

[0018] Intestinal inflammation and barrier dysfunction: Chronic low-grade inflammation and increased intestinal permeability (leaky gut) are associated with the pathogenesis of fatty liver disease. The duodenum is a key site for nutrient absorption and may be affected by various dietary and environmental factors, leading to intestinal inflammation and intestinal barrier disruption. Increased intestinal permeability will allow bacterial products such as lipopolysaccharides (LPS) to translocate into the bloodstream, triggering systemic inflammation and contributing to the development of hepatic steatosis.

[0019] Incretin hormones: As mentioned previously, the duodenum releases incretin hormones, such as GLP-1 and GIP, in response to nutrient intake. These hormones not only regulate glucose homeostasis, but also have effects on lipid metabolism. GLP-1 has been shown to reduce hepatic fat accumulation and improve insulin sensitivity, potentially protecting against fatty liver disease. GIP may also affect lipid metabolism and contribute to the development of hepatic steatosis.

[0020] Nutrient sensing and signaling: The duodenum is a key site for nutrient sensing and signaling, relaying information about nutrient availability to other organs, including the liver. Changes in nutrient composition and absorption in the duodenum can affect signaling pathways involved in lipid metabolism and influence the development of fatty liver disease.

[0021] The duodenal submucosa, the layer beneath the duodenal mucosa, plays a role in glucose homeostasis through several mechanisms. Some of the key mechanisms of action associated with the duodenal submucosa include:

[0022] Enteroendocrine hormone secretion: The duodenal submucosa contains specialized enteroendocrine cells that secrete various hormones involved in glucose regulation. These include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). When nutrients, particularly glucose, encounter the duodenal submucosa, it triggers the release of these hormones into the blood. GLP-1 promotes glucose-dependent insulin secretion from pancreatic beta cells. It also inhibits glucagon secretion from pancreatic alpha cells, slowing gastric emptying and promoting satiety. GIP stimulates the release of insulin from pancreatic beta cells in response to rising blood glucose levels. It enhances nutrient absorption and storage by promoting the release of insulin and inhibiting the secretion of glucagon.

[0023] Neural signaling: The duodenal submucosa is innervated by a neural network, including the enteric nervous system (ENS) and autonomic nerves. These nerves sense and transmit signals related to glucose levels and participate in the regulation of glucose homeostasis. Sensory signals from the duodenal submucosa are transmitted to the brain through neural pathways, thereby regulating pancreatic hormone secretion, hepatic glucose production, and other metabolic processes.

[0024] Nutrient sensing: The duodenal submucosa contains specialized nutrient-sensing cells, such as L cells and K cells. As mentioned previously, these cells can directly sense glucose and other nutrients in the intestinal lumen and respond by releasing hormones such as GLP-1 and GIP. This nutrient sensing helps regulate insulin secretion and other metabolic processes to maintain glucose homeostasis.

[0025] GLP-1 receptor signaling: GLP-1 released from the duodenal submucosa acts on target tissues throughout the body by binding to the GLP-1 receptor. Activation of the GLP-1 receptor has various effects that promote glucose homeostasis, such as stimulating insulin secretion, inhibiting glucagon secretion, enhancing cellular glucose uptake, and improving pancreatic β-cell function.

[0026] Together, these mechanisms contribute to the regulation of glucose homeostasis by the duodenal submucosa. By sensing glucose and other nutrients, releasing enteroendocrine hormones, and transmitting signals to the brain and other target tissues, the duodenal submucosa helps coordinate insulin and glucagon secretion, nutrient uptake and utilization, and other processes involved in maintaining stable blood glucose levels.

[0027] The duodenal submucosal tissue mainly includes blood vessels, nerves and connective tissue, which provide structure and support functions. The duodenal submucosal nerve is a part of the enteric nervous system and plays an important role in regulating glucose homeostasis. The submucosal nerve includes sensory neurons, which can detect changes in the duodenal luminal environment, including the presence of nutrients (such as glucose), and conducts signals to the central nervous system (CNS) and the enteric nervous system (ENS) and the autonomic nervous system (ANS). This allows the coordinated neural signaling that affects glucose metabolism, including insulin secretion, liver glucose production and peripheral glucose uptake. The submucosal nerve also regulates the release of hormones involved in glucose homeostasis. For example, they can stimulate the enteroendocrine cells in the duodenal mucosa to secrete glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). These hormones play a key role in insulin secretion and glucose regulation. The vagus nerve is a major component of the autonomic nervous system, which dominates the duodenal submucosal layer and affects glucose homeostasis by regulating insulin secretion, liver glucose metabolism and intestinal motility. It helps maintain the balance of glucose levels through interactions between the central and enteric nervous systems. The submucosal nerves participate in bidirectional communication between the intestine and the brain, known as the gut-brain axis. This communication pathway allows the integration of signals from the gastrointestinal tract, including glucose-related information, with the CNS. The submucosal nerves play a role in transmitting these signals and influencing the central control of glucose homeostasis. It is clear that the submucosal nerves, as well as other components of the enteric nervous system, play an important role in the neural regulation of glucose metabolism.

[0028] In attempts to treat diabetes, several devices and methods have been developed to bypass or remove a portion of the duodenum. A nonsurgical duodenal–jejunal bypass liner (DJBL) was developed to mimic the proximal small bowel exclusion associated with Roux-en-Y Gastric Bypass (RYGB). The DJBL is a 60-cm-long, impermeable liner that is delivered and retrieved endoscopically. Similar to the RYGB, the DJBL results in significant weight loss and improved glycemic control. Unlike the RYGB, the anatomy of the stomach and small intestine is not affected by DJBL therapy, enabling mechanistic studies that focus specifically on the role of the proximal intestine in T2DM. FIG1 schematically illustrates the location of the DJBL 102 within the duodenum 104. The figure also illustrates the relative locations of the stomach 106 and the esophagus 108.

[0029] Serious adverse events associated with the use of DJBL have been reported, such as gastrointestinal bleeding, device migration, obstruction, and the development of liver abscesses. Liver abscesses are the most serious complication associated with DJBS. The US-FDA trial was stopped by the US Food and Drug Administration (FDA) due to the development of 7 liver abscesses (3.5%), which was much higher than expected. The cause of these liver abscesses is unknown, but it is theorized that the DJBS anchored in the duodenum created an infection nidus, which could spread to the liver bed.

[0030] A surgery called duodenal mucosal resurfacing (DMR) is performed using a specially designed catheter that is advanced on a guidewire near an endoscope. Fig. 2 shows the position of a DMR catheter 202 positioned in the duodenum 204 during a DMR surgery. DMR is a separate minimally invasive endoscopic surgery that involves circumferential hydrothermal ablation of the duodenal mucosa, thereby causing subsequent regeneration of the mucosa. However, thermal ablation of the very thin duodenal mucosa will result in stenosis, bleeding, and perforation. Submucosal saline is injected to prevent deep thermal damage. Other treatments known in the art, including laser, cryoablation, pulsed field ablation, or electroporation, are also used for this surgery.

[0031] In one operation, as shown in FIG3 , a self-assembling magnet 302 is used for seamless compression anastomosis of the small intestine 304, which is less invasive, easy to deliver, and does not leave permanent foreign matter (which occurs in traditional anastomosis techniques). The technique uses a pair of magnets to create a digestive anastomosis, which is performed using an endoscope without the need for surgery. The device is designed to allow a portion of ingested food to move from the beginning of the small intestine jejunum to the end of the small intestine ileum, thereby creating an intestinal diversion and improving glycemic control in diabetic patients. However, the magnet 302 may be incorporated in an undesirable portion of the small intestine, and the proximal end may not be adequately bypassed.

[0032] The above approaches mainly target the intestinal mucosa and do not significantly affect the glucose homeostasis mechanisms associated with the intestinal submucosa, resulting in poor clinical outcomes.

[0033] Bariatric surgery has long been considered a potential treatment for morbid obesity and the metabolic processes that accompany obesity, especially T2D. In the United States, the most commonly used bariatric surgical procedures include laparoscopic and robotic Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). Although surgical treatment is based on the principles of restriction and intestinal malabsorption, there is evidence that more complex mechanisms are at work. Bariatric surgery has been shown to improve blood glucose while allowing a reduction in the use of oral hypoglycemic drugs and insulin, which significantly, rapidly and effectively reverses diabetes in up to 80% of patients. In addition to early postoperative improvements in blood glucose and insulin sensitivity, bariatric surgery has also been shown to cause changes in the release of GI hormones, including ghrelin, leptin, cholecystokinin (CCK), peptide-tyrosine-tyrosine (PYY) and glucagon-like peptide 1 (GLP-1), which may affect feeding behavior through the gut-brain axis in addition to regulating normal blood glucose. Increased levels of insulin-like growth factor 1 (IGF-1) and decreased plasma leptin levels have been observed in both diabetic and nondiabetic morbidly obese patients. Furthermore, microbial changes in the human gut are associated with obesity, and surgical alterations to the gastrointestinal anatomy are associated with significant changes in the gut microbiome, with an “obesogenic” reversion to a lean bacterial community.

[0034] It has been hypothesized that T2D may be the result of an imbalance in the balance between anti-incretin factors and incretins, ultimately leading to a delayed insulin response and impaired insulin action. Figure 4A An imbalance in the balance between anti-incretin factors 401 and incretin factors 403 is schematically shown. Figure 4B It is shown that the anti-incretin factor is most likely overproduced by cells 405, which produce an unknown factor with an anti-incretin effect in the proximal foregut (proximal duodenum) 402 of diabetic patients. Cells 407 that produce calcitonin are also present in the proximal foregut 402 and extend further into the small intestine 406. FIG. 4C shows the stomach 400 and small intestine 410 after gastric bypass surgery, depicting the duodenum 412 separated proximally from the stomach 400 and having a blind proximal pouch and attached distally to the jejunum 414. The proximal portion of the jejunum 414 is attached to the distal end of the stomach 400. The production of GLP-1 and other hormones from the incretin-producing cells 407 is increased, resulting in improved insulin response and action. The reduction of anti-incretin factors produced from the cells 405 that produce the unknown factor with an anti-incretin effect, and the increase in incretin production, lead to normalization of plasma insulin and glucose. Gastric bypass surgery is not without disadvantages. The procedure is invasive and can cause complications. In addition, it is not feasible to perform gastric bypass surgery in all patients with diabetes.

[0035] Bariatric surgery, particularly Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy, has been shown to have a profound effect on improving or even remitting type 2 diabetes. Some of the mechanisms that may explain how bariatric surgery improves diabetes include:

[0036] Weight loss and caloric restriction: Bariatric surgery results in significant weight loss and caloric restriction, which can directly improve insulin sensitivity and glycemic control. The reduction of adipose tissue, especially visceral fat, is associated with improvements in insulin signaling and glucose metabolism.

[0037] Gut Hormone Changes: Bariatric surgery alters the gut hormonal environment, which can have a significant impact on glucose homeostasis. Surgeries such as RYGB and sleeve gastrectomy result in a rearrangement of the gastrointestinal tract, which results in changes in the production and secretion of various gut hormones. These hormonal changes include increased secretion of glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and oxyntomodulin, which promote insulin secretion, enhance insulin sensitivity, suppress appetite, and regulate glucose metabolism.

[0038] Intestinal nutrient sensing: Bariatric surgery alters nutrient flow and absorption patterns in the gastrointestinal tract. Rearrangements of the digestive system can result in accelerated nutrient delivery to the distal intestine, particularly the jejunum and ileum. This nutrient exposure in the lower intestine triggers specific nutrient sensing mechanisms, leading to enhanced insulin secretion, improved glucose uptake, and regulation of hepatic glucose production.

[0039] Gut Microbiota Changes: Bariatric surgery has been shown to induce changes in the composition of the gut microbiota, favoring microbial signatures associated with improved metabolic health. Changes in the gut microbiota following surgery can influence energy extraction from the diet, regulation of gut hormones, and inflammation, all of which can influence glucose homeostasis.

[0040] Insulin-dependent glucose-lowering effects: Bariatric surgery has been shown to have direct effects on glucose metabolism, independent of insulin. This may include increased glucose uptake by peripheral tissues, enhanced hepatic glucose utilization, and improved glucose disposal pathways independent of insulin.

[0041] The overall effect of bariatric surgery on diabetes is likely multifactorial and involves a combination of weight loss, hormonal changes, gut microbiota alterations, and metabolic adaptations, with most of these mechanisms controlled by the intestinal mucosa and submucosa.

[0042] Surgical procedures by resection of the entire intestine target mucosal and submucosal mechanisms and have shown superior results in improving type 2 diabetes, glucose intolerance, and related conditions. These surgeries provide lasting and significant results. However, it is worth noting that these surgeries are highly invasive and expensive and carry a considerable risk of complications and mortality. In addition, once the surgery is performed, it cannot be repeated if it does not produce the desired results. This lack of opportunity for repeat intervention is due to the adaptation or adaptation mechanisms that may occur in the patient, which is another significant negative effect of traditional surgery.

[0043] Therefore, there is a need for less invasive and more practical systems and methods that address the imbalance between anti-incretin factors and incretins by evenly targeting the intestinal mucosa and submucosa without affecting the muscularis and serosa, and thereby treat diabetes, metabolic syndrome, and various conditions associated with insulin resistance. Such systems and methods will be deployed less invasively (e.g., using an endoscope), targeting the mucosa and submucosa, and will not require the removal of intact or full-thickness organs or damage to the full-thickness intestine. In addition, any foreign matter introduced into the body during surgery will be configured to naturally leave the body after the removal is complete, which reduces the risk of complications or does not require repeat surgery. In addition, the surgery can be performed on an outpatient basis, thereby reducing cost and complexity. Minimizing or eliminating the use of thermal energy or other ablation energy required for mucosal ablation surgery will minimize or eliminate complications such as stenosis, bleeding, perforation, and pancreatitis. Summary of the invention

[0044] The following embodiments and aspects thereof are described and illustrated in conjunction with systems, tools, and methods, which are exemplary and illustrative rather than limiting in scope.This application discloses many embodiments.

[0045] The present specification discloses a device for removing body tissue, comprising: a cap configured to be attached to the distal end of an endoscope, wherein the cap includes a central lumen; a suction source configured to apply negative pressure through the central lumen of the cap; and at least one removal component positioned to surround an outer surface of the cap, wherein the at least one removal component has an inner surface including at least one anchor, wherein the at least one removal component includes a first material, the at least one anchor includes a second material, and wherein the first material is different from the second material, wherein the at least one removal component is configured to change from a first configuration when positioned on the cap to a second configuration once deployed, wherein when in the second configuration, the at least one removal component is configured to surround a portion of the body tissue and the at least one anchor contacts the tissue to secure the removal component to shrink the tissue and reduce blood flow to the tissue.

[0046] Optionally, the at least one cutting component comprises a band, a ring, an O-ring, an elastic circle or any other component, which is suitable for having a first structure with a circumference M when subjected to pressure and is suitable for automatically transitioning to a second structure with a circumference N when the pressure is removed, wherein N is less than M.

[0047] Optionally, the anchor comprises a wire of shape memory material, the wire having at least one first portion and at least one second portion, the at least one first portion extending into the at least one cut-away feature, the at least one second portion extending out of the at least one cut-away feature and extending toward a center of the at least one cut-away feature. Optionally, the shape memory material comprises Nitinol. Optionally, in the second configuration, the at least one second portion of the wire is configured to anchor into the body tissue. Optionally, in the second configuration, the at least one second portion of the wire is spike-shaped and configured to pierce the body tissue.

[0048] Optionally, the device comprises 1 to 10 cutting elements.

[0049] Optionally, the device further comprises a conduit extending between the cap and the suction source.

[0050] The specification also discloses a method for removing body tissue in a patient's body, comprising: providing a device configured to pass through an endoscope, the device comprising: a cap portion positioned on a distal end of the device, wherein the cap portion comprises a central lumen; and at least one removal component positioned to surround an outer surface of the cap portion, wherein the at least one removal component has an inner surface comprising at least one anchor, wherein the at least one removal component is configured to change from a first configuration when positioned on the cap portion to a second configuration once the cap portion is deployed, wherein in the second configuration, the at least one removal component is configured to surround a portion of the body tissue, anchored by the anchor, the device being positioned into the tissue to shrink the tissue and reduce blood flow to the tissue; inserting the device into the patient's body through the endoscope and advancing the device so that the distal end of the device is positioned in the patient's gastrointestinal tract; activating a suction source to apply negative pressure through the central lumen of the cap; sucking a portion of the body tissue into the central lumen of the cap, wherein the portion includes at least 1 square centimeter of body tissue; deploying the at least one cutting component from the device around the base of the body tissue; removing the device from the patient; and maintaining the at least one cutting component around the body tissue and cutting off blood flow to the body tissue.

[0051] Optionally, the at least one cutting component comprises a band, a ring, an O-ring, an elastic circle or any other component, which is suitable for having a first structure with a circumference M when subjected to pressure and is suitable for automatically transitioning to a second structure with a circumference N when the pressure is removed, wherein N is less than M.

[0052] Optionally, the anchor comprises a wire of shape memory material, the wire having at least one first portion and at least one second portion, the at least one first portion extending into the at least one cut-away feature, the at least one second portion extending out of the at least one cut-away feature and extending toward a center of the at least one cut-away feature. Optionally, the shape memory material comprises Nitinol. Optionally, in the second configuration, the at least one second portion of the wire is configured to anchor into the body tissue. Optionally, in the second configuration, the at least one second portion of the wire is spike-shaped and configured to pierce the body tissue.

[0053] Optionally, the device comprises 1 to 10 cutting elements.

[0054] Optionally, the device further comprises a conduit extending between the cap and the suction source.

[0055] Optionally, the method is for treating at least one of overweight, obesity, eating disorders, metabolic syndrome, dyslipidemia, diabetes, polycystic ovary disease, fatty liver, non-alcoholic fatty liver disease or non-alcoholic steatohepatitis.

[0056] Optionally, the method further comprises determining a treatment end point after resection.

[0057] Optionally, the treatment endpoint is at least one of a reduction in the patient's total weight by at least 1% relative to the patient's total weight before resection; a reduction in the patient's excess weight by at least 1% relative to the patient's excess weight before resection; a reduction in the patient's total weight by at least 1% relative to the patient's total weight before resection, and a reduction in the patient's health level by no more than 5% relative to the patient's health level before resection; a reduction in the patient's excess weight by at least 1% relative to the patient's excess weight before resection, and a reduction in the patient's health level by no more than 5% relative to the patient's health level before resection; a reduction in the patient's pre-meal gremol level by at least 1% relative to the patient's pre-meal gremol level; a reduction in the patient's post-meal gremol level by at least 1% relative to the patient's post-meal gremol level before resection; or an increase in the patient's exercise output by at least 1% relative to the patient's exercise output before resection.

[0058] Optionally, the treatment endpoint is that the patient's glucagon-like peptide-1 level is increased by at least 1% relative to the patient's glucagon-like peptide-1 level before resection; the patient's leptin level is increased by at least 1% relative to the patient's leptin level before resection; the patient's appetite is reduced within a predetermined time period relative to the patient's appetite before resection; the patient's peptide YY level is increased by at least 1% relative to the patient's peptide YY level before resection; the patient's lipopolysaccharide level is reduced by at least 1% relative to the patient's lipopolysaccharide level before resection; the patient's motilin-related peptide level is reduced by at least 1% relative to the patient's motilin-related peptide level before resection; the patient's cholecystokinin level is reduced by at least 1% relative to the patient's cholecystokinin level before resection, The patient's cholecystokinin level is increased by at least 1%; the patient's resting metabolic rate is increased by at least 1% relative to the patient's resting metabolic rate before resection; the patient's plasma beta-endorphin level is increased by at least 1% relative to the patient's plasma beta-endorphin level before resection; the patient's HbA1c level is reduced by at least 0.3% relative to the patient's HbA1c level before resection; the patient's triglyceride level is reduced by at least 1% relative to the patient's triglyceride level before resection; the patient's total blood cholesterol level is reduced by at least 1% relative to the patient's total blood cholesterol level before resection; or the patient's blood glucose level is reduced by at least 1% relative to the patient's blood glucose level before resection.

[0059] Optionally, the treatment endpoint is a reduction of at least 10% in the patient's daily cumulative dose of antidiabetic drugs relative to the patient's daily cumulative dose of antidiabetic drugs before resection; or elimination of 10% of one or more antidiabetic drugs used by the patient before resection.

[0060] Optionally, the treatment endpoint is a 10% decrease in ALT or AST level relative to pre-resection level; an improvement of at least 10% in serum ferritin level relative to pre-resection level or an absolute serum ferritin level below 1.5 ULN (upper limit of normal) relative to pre-resection level; an improvement of at least 5% or below 5% in hepatic steatosis (HS) relative to pre-resection level, wherein the HS is measured on liver biopsy; an improvement of at least 5% or below 5% relative to pre-resection HS level, wherein the HS is measured by magnetic resonance (MR) imaging, or by spectroscopy or proton density fat fraction; an increase of at least 5% in NAFLD fibrosis score (NFS) relative to pre-resection level; an increase of at least 5% in NAFLD activity score (NAS) relative to pre-resection level; an increase of at least 5% in SAF score relative to pre-resection level; and a reduction of at least 5% in the annual average fibrosis progression rate measured by histology relative to pre-resection level.

[0061] The specification also discloses a device for removing body tissue including gastrointestinal mucosa and submucosa without significantly affecting the muscularis or serosa, comprising: a cap configured to pass through the distal end of an endoscope, wherein the cap includes a central lumen; a suction source configured to apply negative pressure through the central lumen of the cap; and at least one elastic ligation device, such as a rubber band positioned around the outer surface of the cap, wherein the at least one band has an inner surface including at least one anchor, wherein the at least one band is configured to change from a first configuration when positioned on the cap to a second configuration once deployed, wherein in the second configuration, the at least one band is configured to surround a portion of the body tissue and the at least one anchor contacts the tissue to secure the band to shrink the tissue and reduce blood flow to the tissue. The device removes and / or affects the mucosa and submucosa in equal amounts to achieve the desired effect. In other words, the device ablates and / or affects the functionality of the mucosa and the submucosal layer in equal amounts (e.g., within the range of 10% to 90% and any increments therein), such as reduced functionality (including metabolic function), to achieve the desired effect.

[0062] Optionally, the anchor comprises a wire of shape memory material, the wire having at least one first portion extending into the at least one band and at least one second portion extending out of the at least one band and toward a center of the at least one band. Optionally, the shape memory material comprises Nitinol. Optionally, in the second configuration, the at least one second portion of the wire is configured to anchor into the body tissue. Optionally, in the second configuration, the at least one second portion of the wire is spike-shaped and configured to pierce the body tissue.

[0063] Optionally, the device comprises from 1 to 100 bands or ligature devices.

[0064] Optionally, the device further comprises a wire or catheter extending between the cap and the suction source to assist in deployment of the band.

[0065] The specification also discloses a method for removing body tissue from a patient's body, comprising: providing a device configured to be passed through an endoscope, the device comprising: a cap positioned on a distal end of the device, wherein the cap comprises a central lumen; and at least one band or ligation device positioned around an outer surface of the cap, wherein the at least one band or ligation device has an inner surface comprising at least one anchor, wherein the at least one band or ligation device is configured to change from a first configuration when positioned on the cap to a second configuration once the cap is deployed, wherein in the second configuration, the at least one band is configured to surround a portion of the body tissue, using The anchor is anchored into the tissue to shrink the tissue and reduce blood flow to the tissue; inserting the device into the patient through the endoscope and advancing the device so that the distal end of the device is positioned in the duodenum of the patient; activating a suction source to apply negative pressure through the central lumen of the cap; sucking a portion of body tissue into the central lumen of the cap, wherein the portion includes at least 5 square centimeters of body tissue; deploying the at least one band from the device around the base of the body tissue; removing the device from the patient; maintaining the at least one band around the body tissue and cutting off blood flow to the body tissue. The portion of the body tissue is composed of at least mucosal tissue and submucosal tissue.

[0066] Optionally, the anchor comprises a wire of shape memory material having at least one first portion extending into the at least one band or ligation device and at least one second portion extending out of the at least one band or ligation device and toward the center of the at least one band or ligation device. Optionally, the shape memory material comprises nitinol. Optionally, in the second configuration, at least one second portion of the wire is configured to anchor into body tissue. Optionally, when in the second configuration, at least one second portion of the wire is spike-shaped and configured to pierce body tissue. Optionally, the device comprises 1 to 100 bands. Optionally, the device further comprises a catheter extending between the cap and the suction source.

[0067] The method can be used to treat at least one of overweight, obesity, eating disorders, metabolic syndrome, dyslipidemia, diabetes, polycystic ovary disease, fatty liver, non-alcoholic fatty liver disease or non-alcoholic steatohepatitis, or any other disease associated with insulin resistance.

[0068] Optionally, the method further comprises determining a treatment end point after resection. The treatment end point may be at least one of a reduction in the patient's total body weight by at least 1% relative to the patient's total body weight before resection, a reduction in the patient's excess body weight by at least 1% relative to the patient's excess body weight before resection, a reduction in the patient's total body weight by at least 1% relative to the patient's total body weight before resection, and a reduction in the patient's fitness level by no more than 5% relative to the patient's fitness level before resection, a reduction in the patient's excess body weight by at least 1% relative to the patient's fitness level before resection, a reduction in the patient's pre-meal grelin level by at least 1% relative to the patient's pre-meal grelin level before resection, a reduction in the patient's post-meal grelin level by at least 1% relative to the patient's post-meal grelin level before resection, or an increase in the patient's exercise output by at least 1% relative to the patient's exercise output before resection.

[0069] The treatment endpoint may also be an increase of at least 1% in the patient's glucagon-like peptide-1 level relative to the patient's level before resection; an increase of at least 1% in the patient's leptin level relative to the patient's level before resection; a decrease in the patient's appetite over a predetermined period of time relative to the patient's appetite before resection; an increase of at least 1% in the patient's peptide YY level relative to the patient's level before resection; a decrease of at least 1% in the patient's lipopolysaccharide level relative to the patient's level before resection; a decrease of at least 1% in the patient's motilin-related peptide level relative to the patient's level before resection; a decrease of at least 1% in the patient's cholecystokinin level relative to the patient's level before resection. at least one of an increase in the patient's cholecystokinin level by at least 1%; an increase in the patient's resting metabolic rate by at least 1% relative to the patient's resting metabolic rate before resection; an increase in the patient's plasma beta-endorphin level by at least 1% relative to the patient's plasma beta-endorphin level before resection; a decrease in the patient's HbA1c level by at least 0.3% relative to the patient's HbA1c level before resection; a decrease in the patient's triglyceride level by at least 1% relative to the patient's triglyceride level before resection; a decrease in the patient's total blood cholesterol level by at least 1% relative to the patient's total blood cholesterol level before resection; or a decrease in the patient's blood glucose level by at least 1% relative to the patient's blood glucose level before resection.

[0070] The treatment endpoint may also be that the composition of the human intestinal flora is adjusted from a first state before resection to a second state after resection, wherein the first state has a first level of rod-shaped bacteria and a first level of firmicutes, wherein the second state has a second level of rod-shaped bacteria and a second level of firmicutes, wherein the second level of rod-shaped bacteria is at least 3% more than the first level of rod-shaped bacteria, and the second level of firmicutes is at least 3% less than the first level of firmicutes; or, the patient's daily cumulative dose of the anti-diabetic drug is reduced by at least 10% relative to the patient's daily cumulative dose of the anti-diabetic drug before resection.

[0071] The treatment endpoint may also be a 10% decrease in ALT or AST level relative to pre-resection levels; an improvement of at least 10% in serum ferritin levels relative to pre-resection levels or an absolute serum ferritin level below 1.5 ULN (upper limit of normal); an improvement of at least 5% or less than 5% in hepatic steatosis (HS) relative to pre-resection levels, wherein the HS is measured on a liver biopsy; an improvement of at least 5% or less than 5% relative to pre-resection HS levels, wherein the HS is measured by magnetic resonance (MR) imaging, or by spectroscopy or proton density fat fraction; an increase of at least 5% in NAFLD fibrosis score (NFS) relative to pre-resection levels; an increase of at least 5% in NAFLD activity score (NAS) relative to pre-resection levels; an increase of at least 5% in SAF score relative to pre-resection steatosis active fibrosis (SAF) score relative to pre-resection levels; and a decrease of at least 5% in the annual average fibrosis progression rate measured by histology relative to pre-resection levels.

[0072] The treatment endpoint may also be at least one of a 20% reduction in the dose of an oral antidiabetic drug (OAD) or a reduction in the dose of an OAD in at least 20% of the patients.

[0073] The treatment endpoint may also be at least one of a 20% reduction in insulin dose or a reduction in insulin dose in at least 20% of patients, or preventing progression from OAD to insulin therapy in at least 10% of patients.

[0074] The treatment endpoint may also be at least one of a 5% reduction in the incidence of severe hypoglycemic events or a reduction in the incidence of severe hyperglycemic events in at least 25% of the patients.

[0075] The above and other embodiments of the present specification will be described in more depth in the drawings and detailed description provided below. BRIEF DESCRIPTION OF THE DRAWINGS

[0076] The accompanying drawings illustrate various embodiments of systems, methods, and embodiments of various other aspects disclosed. It will be appreciated by those of ordinary skill in the art that the element boundaries (e.g., boxes, box groups, or other shapes) shown in the accompanying drawings represent an example of boundaries. In some examples, an element may be designed as multiple elements, or multiple elements may be designed as one element. In some examples, an element shown as an internal component of an element may be implemented as an external component in another, and vice versa. In addition, an element may be drawn not to scale. Non-restrictive and non-exhaustive descriptions are described with reference to the following drawings. The components in the figure are not necessarily drawn to scale, but emphasize the explanation principle.

[0077] FIG1 schematically shows a duodenal-jejunal bypass liner (DJBL) located in the duodenum;

[0078] FIG2 shows a catheter positioned within the duodenum during a duodenal mucosal resurfacing (DMR) procedure;

[0079] FIG3 shows a system for performing sutureless compression anastomosis positioned in the small intestine using self-assembling magnets;

[0080] Figure 4A An imbalance in the balance between anti-incretin factors and incretins is shown, which is thought to play a pathogenic role in the development of diabetes;

[0081] Figure 4B The foregut depicting the location of antiincretin factor-producing cells and incretin-producing cells in diabetic patients is shown;

[0082] FIG4C shows the stomach and small intestine after gastric bypass surgery;

[0083] Figure 5A The anatomical layout of the proximal digestive system is shown;

[0084] Figure 5B shows a resection device according to some embodiments of the present specification;

[0085] Fig. 6A shows a distal end of an endoscopic device including a resection member or band configured to resect portions of foregut mucosa and submucosa according to some embodiments of the present specification;

[0086] Figure 6B A portion of the foregut mucosa according to some embodiments of the present specification is shown, wherein Fig. 6A After deployment of the device, the resection component or band is placed around the base of the mucosal and submucosal portions;

[0087] Figure 6Cshows a schematic cross-sectional view of a portion of the proximal foregut with a distal end of an endoscopic device positioned within the duodenum and a plurality of foregut mucosa and submucosa portions having a resection member or band positioned around the base of the mucosa and submucosa portions according to some embodiments of the present specification;

[0088] Fig.6D is a flow chart listing the steps involved in resecting mucosal and submucosal tissue using an endoscopic device according to one embodiment of the present specification;

[0089] Fig. 7A The distal end of an endoscopic device for cap-assisted mucosal and submucosal resection according to some embodiments of the present specification is shown;

[0090] Figure 7B Shows Fig. 7A a device wherein a portion of the foregut mucosa and submucosa is drawn into the cap of the device;

[0091] Figure 7C Shows Fig. 7A and Figure 7B The device wherein portions of the foregut mucosa and submucosa are released from the cap and the snare loop is positioned around the base of the mucosa and submucosa portions;

[0092] Fig.7D is a flow chart listing the steps involved in resecting tissue using an endoscopic device according to another embodiment of the present specification;

[0093] Fig. 8A shows a distal end of an endoscopic device according to some embodiments of the present specification having a resection member or band positioned to surround a base of a portion of the foregut mucosa and submucosa;

[0094] Figure 8B Some embodiments according to the present specification are shown Fig. 8A The device wherein the snare loop is positioned around the base of said portion of the foregut mucosa and submucosa;

[0095] Figure 8C Some embodiments according to the present specification are shown Fig. 8A and Figure 8B of a device depicting retraction of the snare loop along with the resected portion of the foregut mucosa and submucosa;

[0096] Fig.8D is a flow chart listing the steps involved in resecting tissue using an endoscopic device according to another embodiment of the present specification;

[0097] Fig.9AAn endoscopic device according to some embodiments of the present specification is shown that is configured to use negative pressure to lift a portion of the foregut mucosa and submucosa and deploy a ligation / resection member or band;

[0098] Fig. 9B is a flow chart listing the steps involved in resecting tissue using an endoscopic device according to another embodiment of the present specification;

[0099] Fig. 10A shows a distal end of an endoscopic device having multiple cutting components / ligatures according to some embodiments of the present specification, wherein a shape memory spike is positioned on the distal end;

[0100] Fig. 10B Shows Fig. 10A a cross-sectional view of a cut-away portion or strip of a device;

[0101] Fig. 10C illustrates a front perspective view of a plurality of cut-out features or bands showing a spike of a shape memory wire extending from the body of each cut-out feature or band toward the center of each cut-out feature or band, according to some embodiments of the present specification;

[0102] Fig.11A shows a cut-out member or band having a shape memory wire positioned within the cut-out member or band in an expanded configuration and a contracted configuration according to some embodiments of the present specification;

[0103] Fig. 11B shows a cut-out member or band having a shape memory wire positioned within the cut-out member or band in an expanded configuration and a contracted configuration according to other embodiments of the present specification;

[0104] Fig. 11C A cut-out member or band having a shape memory wire positioned within the cut-out member or band in a collapsed configuration is shown according to other embodiments of the present specification;

[0105] Fig. 12A shows a cut-out member or band according to some embodiments of the present specification, wherein a plurality of shape memory wire portions are positioned along an inner circumference of the cut-out member or band in an expanded configuration and a contracted configuration;

[0106] Fig. 12B shows a cut-out member or band according to some embodiments of the present specification wherein a plurality of shape memory wires or stainless steel extensions are positioned along an inner circumference of the cut-out member or band in an expanded configuration and a collapsed configuration;

[0107] Fig.13A A cut-out member or strip according to some embodiments of the present specification is shown wherein a plurality of protrusions extend toward the center of the cut-out member or strip in an expanded configuration and a collapsed configuration;

[0108] Fig. 13B shows a cut-out member or strip according to other embodiments of the present specification wherein a plurality of protrusions extend toward the center of the cut-out member or strip in an expanded configuration and a contracted configuration;

[0109] Fig.14A shows a distal end of an endoscopic device including a cylindrical cap according to some embodiments of the present specification, wherein at least two cutting members or elastic bands are positioned around an outer surface of the cap;

[0110] Fig. 14B Some embodiments according to the present specification are shown Fig.14A a resection member or band of the device deployed around the base of the foregut mucosal and submucosal portions;

[0111] Fig.15A An endoscopic resection device according to some embodiments of the present specification is shown, which is positioned to pull the tissue to be resected from its proximal side while cutting the tissue to be resected from the ligation site;

[0112] Fig. 15B The use of some embodiments according to this specification is shown Fig.15A The endoscopic resection device twists and pulls the tissue to be resected;

[0113] Fig. 15C Shows the use of Fig.15A The endoscopic resection device causes the tissue to be resected to lose contact with the intestinal tissue surface;

[0114] Fig.15D multiple views showing deployment of a rotating cutting blade at a ligation site to help separate excised tissue from an intestinal tissue surface in accordance with an embodiment of the present specification; and

[0115] Fig.15E Some embodiments of the present invention illustrate the use of FIG. 15A to FIG. 15D A flowchart of an exemplary set of steps to implement morcellation is provided in accordance with an embodiment of the present invention. DETAILED DESCRIPTION

[0116] The present specification relates to methods and systems for the removal or resection of proximal foregut mucosa and submucosal tissue, and more specifically, to the removal or resection of duodenal mucosa and submucosal tissue. In an embodiment, the imbalance in the balance between anti-incretin factors and incretins caused by the excessive production of anti-incretins is solved by the tissue removal or resection system and method of the present specification. Specifically, the cells in the duodenum responsible for producing factors with anti-incretin effects are removed by selectively resecting the mucosa and submucosal tissue in the duodenum, without removing or resecting the muscularis or serosal tissue as during surgery. Resection or tissue removal surgery is performed in the proximal foregut of diabetic patients. Resection is a medical procedure for removing anatomical structures from the body. In an embodiment of the present specification, a portion of the mucosa and submucosal tissue of the proximal foregut or duodenum is resected or removed. In some embodiments, the mucosa and lower mucosal tissue can be resected.

[0117] Figure 5A The anatomical layout of the digestive system 500 is shown. The proximal foregut in the digestive system 500 includes a portion of the stomach 502, the duodenum 504 and the proximal jejunum 506. The mucus gland layer 514 arranged on the inner wall of the proximal foregut is removed, and the cells 524 that produce anti-incretin factors are eliminated. In addition, the stimulation of more distal intestinal mucosa leads to early and / or excessive production of GLP-1 and other hormones. In addition, glucose homeostasis is regulated by resection of the intestinal submucosa through the neural (CNS, ANS, ENS) pathway and through the above-mentioned neurohumoral pathway. Compared with currently known operations, non-thermal resection or resection of the proximal foregut mucosa and submucosa achieves safer surgery, thereby reducing the side effects of pain, bleeding, perforation or stenosis. Compared with only targeting the mucosal layer, targeting the mucosa and submucosa tissue will have a more profound synergistic effect on glucose homeostasis.

[0118] In some embodiments, a technique in endoscopic band ligation, endoscopic mucosal resection or endoscopic submucosal stripping is used to perform the resection of the foregut mucosa and / or submucosal layer. Elastic or rubber band ligation involves deploying a contraction elastic resection component, device, member, material or band around the mucosal tissue surface to be resected. Deployment of the band around the tissue avoids supplying distal blood to the tissue, so that the affected part slowly necrotizes, falls off and flows out of the body. The endoscopic band ligation procedure involves using a ligation device fixed to the distal end of the endoscope. For this reason, one or more elastic bands are positioned at the distal end. During deployment, the farthest band is stretched outwardly beyond its relaxed configuration and is arranged on the surface of the mucosa in the proximal foregut. In some embodiments, a shape memory material (e.g., nitinol) is positioned together with or within the band loop. Once deployed, the shape memory material contracts, while the elastic band is contracted to its non-stretched configuration, and helps keep the band positioned around the target tissue until ischemic necrosis and / or resection is completed, thereby preventing premature displacement of the band or resection device. In an embodiment, the shape memory material is configured in different forms to provide anchoring into the mucosal surface. The anchoring and contraction of the shape memory material and the contraction of the elastic band enable the loop of the elastic band to gather a portion of the surrounding mucosal surface and submucosal tissue into a nodule. The continued contraction of the anchor and band exerts pressure on the gathered target tissue surface, resulting in the severing of blood supply to the tissue portion, and ultimately leading to necrosis and shedding of the tissue portion. Excision and removal of mucosal and submucosal tissue will target the glucose homeostasis mechanisms located in the mucosa and submucosal layers, thereby producing a more profound synergistic effect on glucose metabolism.

[0119] refer to Figure 5B, a resection device 530 according to an embodiment of the present specification, in particular an "endoscopic device" as defined in the present specification, comprises a catheter 532 having a proximal end 531 and a distal end 533, wherein a suction source 534 is at the proximal end 531 of the catheter 532, and a cap 536 is at the distal end 533 of the catheter 532. The catheter 532 is configured to pass through a working channel of an endoscope 540. The cap 536 is configured to pass through the distal end of the endoscope 540 and includes a central lumen 537. The suction source 534 is activated to apply negative pressure via the central lumen 537 of the cap 536 to suck tissue into the cap. At least one resection member or band 538 is positioned around the outer surface of the cap 536 and is configured to change from a first configuration when positioned on the cap 536 to a second configuration once deployed. In the second configuration, at least one band 538 is configured to surround a portion of body tissue to shrink the tissue and reduce blood flow to the tissue. The tissue eventually necrotizes, falls off, and passes through the gastrointestinal tract. In some embodiments, at least one band 538 includes at least one anchoring mechanism 539 to help secure at least one band 538 to the tissue. In some embodiments, at least one anchor 539 includes a shape memory wire or coil. In some embodiments, the shape memory material is nitinol. Resection of the foregut mucosa and / or submucosa triggers regeneration of healthy foregut mucosa and / or submucosa, which will not have diseased cells that cause insulin resistance and dysregulated blood glucose homeostasis.

[0120] Resection of the foregut mucosa or submucosa and regeneration of normal / healthy foregut mucosa and / or submucosa results in and increases intestinal glucagon and gastric inhibitory peptide responses to oral glucose, increases insulin-like growth factor 1 levels (IGF-1), and reduces plasma leptin levels in diabetic and non-diabetic morbidly obese patients, similar to those observed in gastric bypass surgery. Gastric bypass achieves normalization of plasma insulin and glucose by avoiding stimulation of cells that produce unknown factors with anti-incretin effects, as well as earlier and / or excessive production of GLP-1 and other hormones. Postprandial reduction of pancreatic polypeptide may also occur. Resection of the foregut mucosa / submucosa reduces leptin levels before weight loss and increases intestinal glucagon responses to glucose tests, similar to the results of biliopancreatic diversion. The embodiments of the present specification reduce plasma lipid levels, which are similar to plasma lipid levels in biliopancreatic diversion in some patients. The high levels of plasma glucagon-like peptide 1 reported after jejunoileal bypass can also be observed by resection of the foregut mucosa / submucosa using the devices and methods of the present specification. High levels of plasma glucagon-like peptide 1 play a role in the mechanism of diabetes control after bariatric surgery and also lead to improvement or regression of many conditions associated with insulin resistance.

[0121] This specification is directed to multiple embodiments. In order to enable those of ordinary skill in the art to practice the present invention, the following disclosure is provided. The language used in this specification should not be interpreted as a general negation of any one specific embodiment or used to limit the claims beyond the meaning of the terms used therein. Without departing from the spirit and scope of the present invention, the general principles defined herein may be applied to other embodiments and applications. In addition, the terms and phrases used are used for the purpose of describing exemplary embodiments and should not be considered restrictive. Therefore, the present invention will be given the broadest scope, including many replacements, modifications and equivalents consistent with the disclosed principles and features. For the sake of clarity, details related to technical materials known in the technical field related to the present invention are not described in detail to avoid unnecessary limitations on the present invention.

[0122] In the specification and claims of the present application, each word "includes", "has", "comprising" and various forms thereof are not necessarily limited to the elements in the list with which these words can be associated. Therefore, they are equivalent in meaning and open-ended, in that any one of these words followed by one or more items does not mean an exhaustive list of the one or more items, or means limited to the one or more items listed. It should be noted that any feature or component described in connection with a particular embodiment can be used and implemented with any other embodiment unless otherwise explicitly indicated.

[0123] It must also be noted that, as used herein and in the appended claims, the singular forms "a," "an," and "the" include plural references unless the context dictates otherwise. Although any systems and methods similar or equivalent to those described herein can be used in the practice or testing of embodiments of the present disclosure, the preferred systems and methods are now described.

[0124] In this specification, the term "resection member" is defined as any elastic resection member, device, component or material that is configured to be positioned around a tissue surface, such as via deployment of a deployment device, to surround or wrap a portion of the tissue to be resected. The resection member includes a band, a ring, an O-ring, an elastic circle or any other member that is adapted to have a first configuration with a circumference M when subjected to pressure, and is adapted to automatically transition to a second configuration with a circumference N when the pressure is removed, wherein N is less than M.

[0125] Insulin resistance can be assessed by various clinical and laboratory parameters. Some common parameters used to measure insulin resistance include:

[0126] Fasting insulin: Fasting insulin levels are measured after an overnight fast and provide an indication of basal insulin secretion. Elevated fasting insulin levels are often associated with insulin resistance.

[0127] Fasting blood glucose: Fasting blood glucose levels are measured to assess the fasting state of glucose metabolism. Insulin resistance can lead to worse fasting blood glucose levels, which indicates that insulin is less able to promote glucose uptake.

[0128] Homeostasis model assessment of insulin resistance (HOMA-IR): HOMA-IR is a mathematical formula that calculates insulin resistance using fasting blood glucose and fasting insulin levels. It provides an estimate of insulin sensitivity based on the assumption that the liver is the primary site of insulin resistance.

[0129] Oral glucose tolerance test (OGTT): An OGTT involves measuring blood sugar and insulin levels before and after ingesting a glucose solution. The response of blood sugar and insulin after glucose ingestion can help assess insulin resistance.

[0130] Insulin Sensitivity Index (ISI): The ISI is a measure of whole-body insulin sensitivity and can be obtained from a hyperinsulinemic-euglycemic clamp or a frequently sampled intravenous glucose tolerance test (FSIVGTT). It provides a quantitative assessment of insulin sensitivity.

[0131] Quantitative Insulin Sensitivity Check Index (QUICKI): QUICKI is a formula that uses fasting blood glucose and fasting insulin levels to estimate insulin sensitivity. It is based on the inverse relationship between insulin sensitivity and fasting insulin levels.

[0132] Matsuda Index: The Matsuda Index is calculated from glucose and insulin values ​​obtained during an OGTT. It provides an estimate of insulin sensitivity by assessing the ability of insulin to promote glucose disposal.

[0133] Adipose tissue insulin resistance (Adipo-IR): Adipo-IR is a measure of adipose tissue-specific insulin resistance. It is calculated using fasting plasma insulin and adiponectin levels, with lower adiponectin levels indicating higher adipose tissue insulin resistance.

[0134] Insulin clamp technique: The hyperinsulinemic-euglycemic clamp technique is considered the gold standard for measuring insulin sensitivity. It involves intravenous infusion of insulin at a constant rate while maintaining blood glucose levels at a stable, predetermined level.

[0135] Lipid profile: Insulin resistance is often associated with alterations in lipid metabolism. Assessment of parameters such as triglycerides, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol can provide insight into metabolic abnormalities associated with insulin resistance.

[0136] Waist circumference and body mass index (BMI): Central obesity is strongly associated with insulin resistance. Waist circumference and BMI are simple anthropometric measures used to assess obesity and estimate the risk of insulin resistance.

[0137] One or more of these parameters can be used to provide a comprehensive assessment of insulin resistance. Different techniques and indices may be used in research and clinical settings based on availability and specific research or diagnostic purposes. An improvement in insulin resistance of 10% or more measured using any of these parameters is clinically significant and meaningful.

[0138] The severity of nonalcoholic fatty liver disease (NAFLD) is assessed using several clinical and laboratory tests. These tests help assess the extent of liver damage, inflammation, fibrosis, and other related aspects. Common tests used to measure the severity of NAFLD include:

[0139] Liver function tests: Elevated ALT levels are a marker of liver inflammation and damage. Higher ALT levels often indicate more severe liver damage in NAFLD.

[0140] Imaging studies - Ultrasound is a non-invasive imaging technique that can detect fat accumulation in the liver and is an initial screening tool for NAFLD. Computed tomography (CT) provides detailed images of the liver and helps assess the extent of fat deposits and fibrosis. Magnetic resonance imaging (MRI) can assess liver fat content, fibrosis, and inflammation, providing more precise information about the severity of NAFLD. Transient elastography (FibroScan) measures liver stiffness, which is an indirect marker of the severity of fibrosis. Higher liver stiffness values ​​indicate more severe fibrosis.

[0141] Biomarkers of fibrosis and inflammation include fibrosis-4 index (FIB-4), which is a simple calculation that combines age, AST (aspartate aminotransferase) level, ALT level and platelet count to estimate the degree of liver fibrosis. Higher FIB-4 scores are associated with more severe fibrosis. NAFLD fibrosis score uses several clinical parameters, including age, BMI, diabetes status, platelet count, albumin level and AST / ALT ratio, to predict the presence and severity of liver fibrosis. Enhanced liver fibrosis (ELF) test measures three serum markers (hyaluronic acid, procollagen type III N-terminal peptide and tissue inhibitor of metalloproteinase 1) associated with liver fibrosis. It provides a digital score indicating the severity of fibrosis.

[0142] A liver biopsy is considered the gold standard for assessing the severity of NAFLD. A small sample of liver tissue is obtained and examined under a microscope to determine the extent of fat accumulation, inflammation, liver cell damage, and fibrosis.

[0143] The choice of test depends on the clinical context, resources, and individual patient factors. Noninvasive methods are preferred whenever possible, but in some cases, liver biopsy may be necessary to provide a definitive assessment of the severity of NAFLD.

[0144] One or more of these parameters can be used to provide a comprehensive assessment of NAFLD. Different techniques and indices may be used in research and clinical settings based on availability and specific research or diagnostic purposes. An improvement in insulin resistance of 10% or more measured using any of these parameters is clinically significant and meaningful.

[0145] Fig. 6A , Figure 6B and Figure 6C Resection of the foregut mucosa using a ligation or resection device such as an elastic band is depicted. Fig. 6A The distal end of an endoscopic device 604 is shown including a resection member or band 602 configured to resect portions of the foregut mucosa, according to some embodiments of the present specification. Figure 6B A portion 603 of the foregut mucosa is shown, wherein the Fig. 6A After the device is deployed, band 602 surrounds the base of the mucosal portion 603. Figure 6C A schematic cross-sectional view of a portion of the proximal foregut is shown, wherein the distal end of an endoscopic device 604 is positioned within the duodenum 601, and a plurality of foregut mucosa and submucosa portions 603 have bands positioned around the base of the mucosa portions. Although elastic bands are depicted as a preferred method for resecting the mucosa and / or submucosa, other resection devices and / or techniques known in the art may also be used to resect and / or dissect the foregut mucosa and / or submucosa. In all resection methods, the foregut muscularis propria and adventitia or serosa that remain are functional and intact, and the submucosa and mucosa are subsequently regenerated to restore the normal structure and / or function of the target foregut.

[0146] Also refer to Fig. 6A , Figure 6B and Figure 6C, the endoscopic device 604 includes a distal end or cap 606, wherein one or more ligating devices such as a band 602 are positioned around the cap 606. In an embodiment, one or more bands 602 are elastic bands that are stretched when positioned around the cap 606 and contract once deployed around a section of mucosa. In some embodiments, the endoscopic device is configured to suck a portion of the mucosa into the cap 606, and then deploy the band 602 around the base of the mucosal portion 603 sucked into the cap 606. In some embodiments, a suction device is applied to the endoscopic device 604 to suck the mucosal portion 603 into the cap 606. In some embodiments, one or more bands 602 include an anchor 608 that is configured to grasp or pierce the mucosal portion 603 and help keep the band 602 in place and prevent premature sliding of the band after deployment. In some embodiments, the cap 606 is transparent. Figure 6B A mucosal portion 603 is shown being drawn into the cap 606 through a transparent cap 606, with the band 602 positioned around the base of the mucosal portion 603. In another embodiment, another resection device or method can be used to resect the foregut mucosa and / or submucosa. In yet another device, a mechanical morcellation device can be used to remove the intestinal mucosa and submucosa.

[0147] refer to Figure 6C , which depicts multiple mucosal and submucosal sections 603 with bands 602 surrounding each base of each section. The elastic properties of the bands 602 cause them to contract around the base of each mucosal section 603, effectively cutting off the blood supply to the mucosal and submucosal sections 603. Each captured section 603 eventually necrotizes, falls off, and passes through the GI system. Over the next few days to a week or more, the resected area regenerates with improved function and structure, thereby improving glucose homeostasis and insulin resistance.

[0148] Fig.6D It is a flowchart of the steps involved in using an endoscopic device to excise or remove tissue according to an embodiment of the present specification. In step 620, the endoscopic device is inserted into the patient and advanced so that the distal end of the device is positioned in the duodenum of the patient. In step 622, a part of the duodenal mucosa is sucked into the cap at the distal end of the endoscopic device. In step 624, at least one band is deployed from the distal end of the endoscopic device and positioned to surround the base of the mucosal portion. In step 626, the endoscopic device is removed from the patient, allowing the band to retain and cut off the blood flow to the mucosal portion, which eventually necrotizes and falls off. In the following days to a week or longer, the excision area is regenerated with improved and / or normal function and / or structure. In another embodiment, a morcellation device passing through the channel of the endoscope can be used to excise / remove intestinal mucosa and / or submucosal tissue.

[0149] Fig. 7A , Figure 7B and Figure 7C Shown is the progression of cap-assisted foregut mucosal resection. Fig. 7A The distal end of an endoscopic device 704 for cap-assisted mucosal and submucosal resection according to some embodiments of the present specification is shown. The endoscopic device 704 includes a distal end or cap 706 and is configured to allow a snare device 712 to pass through a working channel of the endoscopic device 704 and extend through and beyond the cap 706. The distal end or cap 706 of the endoscopic device 704 is positioned proximate to a target tissue or mucosal portion 703 of the duodenum 701 of a patient. In some embodiments, the cap 706 is transparent. Figure 7B Shows Fig. 7A The endoscopic device 704 is a device for removing a portion of the foregut mucosa 703 from the endoscopic apparatus 704, wherein a portion of the foregut mucosa 703 is drawn into the cap 706 of the device 704. A resection component including a snare loop or wire 722 extends from the snare device 712 and surrounds the base of the mucosal portion 703. In some embodiments, the endoscopic device 704 is configured to draw a portion of the mucosa 703 into the cap 706. In some embodiments, a suction device is applied to the endoscopic device 704 to draw the mucosal portion 703 into the cap 706. Submucosal lifting agents known in the art may be used to assist in the resection / removal of tissue.

[0150] Figure 7C Shows Fig. 7A and Figure 7B Endoscopic device 704, wherein a portion of the foregut mucosa 703 is released from the cap 706 and the snare loop or wire 722 is positioned around the base of the mucosal portion 703. The snare loop or wire 722 has been retracted into the snare device 712, so that the snare loop or wire is tightened to shrink the base of the mucosal portion 703, thereby effectively cutting off the blood supply to the mucosal portion 703. In some embodiments, the snare loop or wire 722 is completely retracted into the snare device 712, which cuts the mucosal portion off from the duodenal wall, thereby resecting the mucosal portion 703. In some embodiments, an electric current is provided to the snare loop or wire to heat the wire and help cut the tissue (hot snare resection). If no electric current is provided, the resection is referred to as cold snare resection. The resected portion can then be removed from the patient. In other embodiments, a clamp may be applied to the contracted base of the mucosal portion 703. The mucosal portion lacks blood supply and eventually necroses and falls off. Over the next few days to a week or more, the resected area regenerates with improved function and / or structure.

[0151] Fig.7Dis a flow chart listing the steps involved in resecting tissue using an endoscopic device according to another embodiment of the present specification. In step 720, the endoscopic device is inserted into the patient's body and advanced so that the distal end of the device is positioned in the patient's duodenum. In step 722, a snare device is passed through the working channel of the endoscopic device, and the distal end of the snare device is positioned close to the mucosal portion. In step 724, a snare loop or wire is positioned around the base of the mucosal portion and is tightened to retract the mucosa and submucosal tissue. In step 726, optionally, the snare loop with captured mucosa and submucosal tissue is retracted into a cap at the distal end of the endoscopic device. In step 728, the snare loop or wire cuts off the base of the mucosal portion, and the resected mucosal portion is removed from the patient's body or allowed to pass naturally through the patient.

[0152] Fig. 8A , Figure 8B and Figure 8C Shown is the progression of foregut mucosal resection using a band and snare. Fig. 8A The distal end or cap 806 of an endoscopic device 804 is shown according to some embodiments of the present specification, wherein a cutting member or band 802 is positioned around the base of a portion of foregut mucosa 803. In some embodiments, the endoscopic device 804 is configured to draw the portion of mucosa 803 into the cap 806. In some embodiments, a suction device is applied to the endoscopic device 804 to draw the mucosal portion 803 into the cap 806. Once deployed, the cutting member or band 802 returns to its non-stretched state due to its elastic properties and contracts around the mucosal portion 803, cutting off the blood supply to the mucosal and submucosal tissue 803 and forming a polyp-like lesion.

[0153] Figure 8B Some embodiments according to the present specification are shown Fig. 8AThe endoscopic device 804 is configured to allow the snare device 812 to pass through the working channel 816. In one embodiment, the snare loop or wire 822 of the snare device 812 is extended and positioned around the base of the contracted mucosal portion 803. In some embodiments, the snare loop or wire 822 is positioned below the previously placed band 802. The snare loop or wire 822 is pulled back into the snare device 812, causing the snare loop or wire 822 to contract around the base of the mucosal portion 803. In some embodiments, after the band 802 is set, the snare loop or wire 822 is used to contract and cut the base of the mucosal portion 803, thereby resecting the mucosal portion 803. In some embodiments, an electric current is provided to the snare loop or wire to heat the wire and help cut tissue (thermal snare resection). In other embodiments, the band 802 is initially deployed and allowed to cut off blood flow to the mucosal portion 803. Over time, blood flow to the contracted tissue is blocked and the tissue gradually necrotizes due to the pressure applied by the deployed band 802. The endoscopic device 804 is then reinserted into the patient and the mucosal portion 803 that has necrotized due to lack of blood flow is removed using the snare loop or wire 822. Figure 8C Some embodiments according to the present specification are shown Fig. 8A and Figure 8B An endoscopic device 804 is shown depicting the retraction of a snare loop or wire 822 along with a resected portion of foregut mucosa 803 over which a band 802 is disposed.

[0154] Fig.8D is a flowchart listing the steps involved in resecting tissue using an endoscopic device according to another embodiment of the present specification. In step 820, the endoscopic device is inserted into the patient's body and advanced so that the distal end of the device is positioned in the patient's duodenum. In step 823, a portion of the duodenal mucosa is sucked into the cap at the distal end of the endoscopic device. In step 824, at least one band is deployed from the distal end of the endoscopic device and positioned around the base of the mucosal portion. In step 826, a snare device is passed through the working channel of the endoscopic device, and the distal end of the snare device is positioned close to the mucosal portion. In step 828, a snare loop or wire is positioned around the base of the mucosal portion and is tightened to shrink the mucosal portion. In step 830, the snare loop or wire cuts off the base of the mucosal and submucosal portions, and the resected mucosal and submucosal tissue is removed from the patient's body.

[0155] Fig.9AAn endoscopic device 904 according to some embodiments of the present specification is shown, which is configured to use negative pressure or suction pressure to lift a portion of the foregut mucosa 903 and deploy a resection component / ligature 902. The endoscopic device includes a cap 906 at its distal end. The endoscopic device 904 is inserted into the patient's body and manipulated to the location of the target tissue or mucosal portion 903, as shown in step A. Negative pressure is applied to the endoscopic device 904 to suck the mucosa and submucosal tissue 903 into the cap 906. Negative pressure is maintained to keep the mucosal portion 903 within the cap 906. In some embodiments, the negative pressure within the cap is activated by a control disposed at the proximal end of the endoscopic device. In step B, the distal end of the endoscopic device 904 is lifted while maintaining negative pressure to lift the mucosal portion 903. In step C, while maintaining negative pressure, deploy one of the one or more bands or ligator 902 positioned on the outer surface of the cap 906 and position it around the base of the mucosa and submucosal tissue 903. In some embodiments, the user can actuate the release mechanism of the band according to the control set at the proximal end of the endoscopic device. In some embodiments, a pair of wires 907 extending from the proximal end of the device to the radially opposite sides of the band 902 are used to pull and deploy the band 902 so that the band 902 slides out of the cap 906 and reaches the tissue. Release and position the band to form a loop around the base of the mucosal portion 903. In step D, the negative pressure is released so that the mucosal portion 903 is released from the cap 906, and the band contracts the mucosal portion 903. The elastic properties of the band 902 make it tighten around the base of the mucosal portion 903, thereby cutting off the blood supply to the portion. The mucosa and submucosal tissue 903 eventually necrotize and fall off, leaving the intact muscularis propria and serosa.

[0156] Fig. 9B is a flow chart listing the steps involved in removing tissue using an endoscopic device according to another embodiment of the present specification. In step 920, the endoscopic device is inserted into the patient and advanced so that the distal end of the device is positioned in the duodenum of the patient. In step 922, negative pressure is applied to the endoscopic device to draw a portion of the duodenal mucosa into the cap at the distal end of the endoscopic device. In step 924, the distal end of the endoscopic device is lifted while maintaining negative pressure to lift the mucosal portion. In step 926, at least one band is deployed from the distal end of the endoscopic device and positioned around the base of the mucosal portion. In step 928, the negative pressure is released and the mucosal portion is released from the cap of the endoscopic device. In step 930, the endoscopic device is removed from the patient, allowing the band or ligation device to be retained and blood flow to the mucosa and submucosal tissue is cut off, which eventually necrotizes and falls off.

[0157] In various embodiments of the present specification, the end cap positioned at the distal end of the endoscope can be made of one or more of polycarbonate, PVC, silicone, or Teflon non-latex rubber materials. The end cap is preferably made of a transparent material to make the surgical procedure visible. In an embodiment, the diameter of the end cap is in the range of 5 mm to 25 mm. Additionally, in an embodiment, the band configured to be positioned on the end cap is made of one of silicone, Teflon rubber, or non-latex rubber.

[0158] Fig. 10A The distal end of an endoscopic device 1000 having a plurality of cutting components or bands 1012 is shown, wherein a shape memory spike is positioned on the distal end, according to some embodiments of the present specification. The endoscopic device 1000 includes an end cap 1002, which in an embodiment is an elongated cylindrical structure having three sections along its longitudinal length. A first proximal portion 1004 is used to attach the end cap portion 1002 to the distal end of the endoscope. A second distal portion 1006 includes a transparent cylindrical wall having an opening on its distal side. In some embodiments, a portion 1008 of the circumference of the opening is serrated, while the remaining circumference is smooth. The serrated containment line 1016 is positioned along the longitudinal surface of the end cap 1002 and pulls the cutting band 1012, and prevents the band 1012 from sliding along the circumferential surface of the end cap 1002 (similar to a pulley groove). The third middle portion 1010, which is located between the first portion 1004 and the third portion 1006 and connects the first portion 1004 and the third portion 1006, includes one or more elastic excision bands 1012 positioned around the outer surface of the cap 1002. In an embodiment, each elastic band 1012 is designed to be in the shape of a ring, with a hollow portion in the cylindrical ring of the band 1012. In an embodiment, during manufacture, the material of the band 1012 is molded onto a shape memory wire (e.g., nitinol). The combination of the band 1012 and the wire (wire 1014) provides the compression function required for excision. In addition, the wire 1014 provides the ability to anchor into the tissue while preventing the band 1012 from sliding prematurely, thereby causing complete ischemic necrosis and subsequently peeling off the tissue around the band. Fig. 10B A cross-sectional view of the band 1012 is shown. Wire 1014 extends through various portions of the band 1012 and various segments of the wire extend into the central hollow portion 1013 of the band 1012, passing through holes punched in the surface of the band 1012. In an embodiment, the wire 1014 is made of a shape memory alloy (e.g., Nitinol). In its original compressed form, the wire 1014 forms a spike 1024 with a peak that points toward the hollow center 1013 of the band 1012, and a groove 1026 within the band 1012. The wire 1014 forms a closed loop. Fig. 10CA front perspective view of a plurality of straps 1012 is shown showing spikes of shape memory wire 1014 extending from the body of each strap toward the center of each strap, according to some embodiments of the present specification. FIG. 10A to FIG. 10C , once the band 1012 is deployed, it is configured to be positioned around a portion of the mucosal tissue and cut off the blood supply from a portion of the mucosal tissue. In an embodiment, the band 1012 is stretched into a first configuration and arranged on the cap 1002. After deployment, the elastic properties of the band 1012 cause them to shrink into a second configuration around the base of the mucosal portion. In an embodiment, when the band 1012 is in the first configuration, the band 1012 has a first diameter, and when the band 1012 is in the second configuration, the band 1012 has a second diameter. In an embodiment, the first diameter is greater than the second diameter. The line 1014 within the band 1012 is configured to change its shape from the first configuration when the band 1012 is positioned on the cap 1002 to the second configuration when the band is deployed on the mucosal portion. When in the first configuration, the shape and size of the line 1014 are designed so that it allows the band 1012 to be arranged on the cap 1002 at the maximum extension position of the band. In other words, when the wire 1014 is in the first configuration, the wire has a rounded shape similar to the shape of the stretch band in the first configuration. When the wire 1014 is in the second configuration, its shape changes to include peaks or spikes 1024 that protrude into, grab or pierce the mucosal portion to help hold the band 1012 around tissue. In addition, the wire is shaped so that the band in the second configuration is maximally retracted without significantly interfering with the retraction process.

[0159] Fig.11AA cutting member or band 1112 is shown according to some embodiments of the present specification, wherein a shape memory wire 1114 is positioned within the band in an extended configuration and a contracted configuration. In some embodiments, the band 1112 has a first diameter in the range of 1 mm to 5 mm and a first thickness in the range of 1 mm to 5 mm in its contracted state, and has a second diameter in the range of 5 mm to 25 mm and a second thickness in the range of 0.5 mm to 2.5 mm in its extended state. The wire 1114 is located inside the band 1112 so that a first wire portion 1104 is located inside the band 1112 and in contact with the material of the band 1112, a second wire portion 1124 extends from the band 1112 and toward the center of the band 1112, and a third wire portion 1134 extends from the band 1112 and away from the center of the band 1112. In the first configuration depicted in view 1118, the band 1112 is stretched to be disposed on the cap of the endoscopic device. The band 1112 in the first configuration is a circular shape having a first diameter. The wire 1114 in the first configuration approximates the shape of the band 1112. After deployment, the band 1112 changes from the first configuration in view 1118 to the second configuration depicted in view 1120. The elastic properties of the band 1112 in the second configuration cause the band 1112 to contract. The band 1112 in the second configuration has a circular shape and a second diameter. In an embodiment, the second diameter is less than the first diameter. The second wire portion 1124 in the second configuration forms a spike or protrusion configured to grasp or pierce the mucosal portion surrounded by the band 1112. The second wire portion 1124 or spike in the second configuration helps to keep the band 1112 set on the mucosal portion. In some embodiments, the shape-changing properties of the wire 1114 help to contract the band 1112. In addition, the spike extends roughly perpendicular to the inner diameter of the band before deployment, and the spike extends roughly parallel to the inner diameter of the band in the deployed position.

[0160] Fig. 11B A cut-away member or band 1142 is shown in accordance with other embodiments of the present description wherein a shape memory wire 1144 is positioned within the band in an expanded configuration and a collapsed configuration. Fig. 11C A belt according to some embodiments of the present specification is shown, wherein a shape memory wire in a collapsed configuration is positioned within the belt. Fig. 11B and Fig. 11C, the line 1144 is positioned within the band 1142 so that the first line portion 1154 is located within the band 1142 and in contact with the material of the band 1142, and the second line portion 1164 extends from the band 1142 to the center of the band 1142. In the first configuration depicted in view 1158, the band 1142 is stretched to be set on the cap of the endoscopic device. The band 1142 in the first configuration is a circular shape with a first diameter. The line 1144 in the first configuration approximates the shape of the band 1142. After deployment, the band 1142 changes from the first configuration in view 1158 to the second configuration depicted in view 1160. The elastic properties of the band 1142 in the second configuration cause it to shrink. The band 1142 in the second configuration has a circular shape and a second diameter. In an embodiment, the second diameter is less than the first diameter. In the second configuration, the second line portion 1164 forms a spike or protrusion configured to grasp or pierce the mucosal portion surrounded by the band 1142. In the second configuration, the second wire portion 1164 or spikes serve as anchors and help keep the band 1142 positioned on the mucosal portion, thereby preventing premature displacement of the band 1142. In some embodiments, the shape-changing properties of the wire 1144 help to retract the band 1142.

[0161] In various embodiments, including FIG. 11A to FIG. 11C As shown, during the compressed state of the shape memory material, a band comprising a shape memory material is forced to compress. The band is compressed around the mucosa and submucosal portion, or around a pseudopolyp, which is supported by a shape memory element according to an embodiment of the present specification. The compression of the band promotes anchoring of the band around the pseudopolyp in the mucosal tissue for the purpose of resection. The shape memory material prevents the elastic material of the band around the tissue from being displaced prematurely.

[0162] Fig. 12AA cut-out component or band 1212 according to some embodiments of the present specification is shown, wherein a plurality of shape memory wire portions 1214 are positioned along the inner circumference of the band 1212 in an expanded configuration and a contracted configuration. In an embodiment, the wire portion 1214 is positioned as a protrusion along the inner circumference of the band 1212 and extends from the band and toward the center of the band. The wire portion 1214 is attached to the band 1212, the adhesive band 1212, or molded on the band 1212 so that the expansion and contraction of the two structures are almost the same. In an embodiment, the spikes of the wire 1214 can all be connected together as a structure, or can include multiple disconnected spikes. In the first configuration depicted in view 1218, the band 1212 is stretched to be set on the cap of the endoscopic device. The band 1212 in the first configuration is a circular shape having a first diameter. In an embodiment, the wire portion 1214 in the first configuration is a mountain shape. In an embodiment, the band 1212 includes one to ten wire portions 1214. In an embodiment, the band 1212 includes four wire portions 1214. After deployment, band 1212 changes from the first configuration in view 1218 to the second configuration depicted in view 1220. The elastic properties of band 1212 in the second configuration cause band 1212 to contract. Band 1212 in the second configuration has a circular shape and a second diameter. In an embodiment, the second diameter is less than the first diameter. The wire portion 1214 in the second configuration forms a spike configured to grasp or pierce the mucosal portion surrounded by band 1212. The wire portion 1214 or spike in the second configuration serves as an anchor and helps to keep band 1212 set on the mucosal portion, thereby preventing band 1212 from being displaced prematurely. In some embodiments, the shape-changing properties of wire 1214 help to contract band 1212.

[0163] Fig. 12BA cutting member or band 1222 is shown according to some embodiments of the present specification, wherein a plurality of shape memory or stainless steel wire extensions or spikes 1224 are positioned along the inner circumference of the band 1222 in an expanded configuration and a contracted configuration. In an embodiment, the wire extensions 1224 are positioned as protrusions along the inner circumference of the band 1222 and extend from the band and toward the center of the band. The band 1222 in the first configuration depicted in view 1228 is stretched to be disposed on the cap of the endoscopic device. The band 1222 in the first configuration is a circular shape having a first diameter. In an embodiment, the wire extensions 1224 in the first configuration are tower-shaped or cylindrical. In some embodiments, the wire extensions 1224 include a spike or serrated distal end 1226. In an embodiment, the band 1222 includes one to ten wire extensions 1224. In one embodiment, the band 1222 includes four wire extensions 1224. After deployment, the band 1222 changes from the first configuration in view 1228 to the second configuration depicted in view 1230. The elastic properties of the band 1222 in the second configuration cause the band 1222 to contract. The band 1222 in the second configuration has a circular shape and a second diameter. In an embodiment, the second diameter is less than the first diameter. The wire extension 1224 in the second configuration forms a spike configured to grasp or pierce the mucosal portion surrounded by the band 1222. The wire extension 1224 or spike in the second configuration acts as an anchor and helps to keep the band 1222 on the mucosal portion, thereby preventing the band 1222 from being displaced prematurely.

[0164] Fig.13AA cutting member or band 1312 is shown according to some embodiments of the present specification, wherein a plurality of protrusions 1314 extend toward the center of the band in an extended configuration and a contracted configuration. In an embodiment, the protrusions 1314 are part of the elastic band 1312, made of the same or different material as the band, and are positioned along the inner circumference of the band 1312, extending from the band and toward the center of the band. The band 1312 in the first configuration depicted in view 1318 is stretched to be set on the cap of the endoscopic device. The band 1312 in the first configuration is a circular shape having a first diameter. In an embodiment, the protrusions 1314 in the first configuration are mountain-shaped with a first base diameter and a first height. In an embodiment, the band 1312 includes one to ten protrusions 1314. In one embodiment, the band 1312 includes four protrusions 1314. After deployment, the band 1312 changes from the first configuration in view 1318 to the second configuration depicted in view 1320. The elastic properties of the band 1312 in the second configuration cause the band 1312 to contract. The band 1312 in the second configuration has a circular shape and a second diameter. In an embodiment, the second diameter is less than the first diameter. In an embodiment, the protrusion 1314 in the second configuration is a mountain shape with a second base diameter and a second height. In an embodiment, the second base diameter is less than the first base diameter and the second height is greater than the first height. The protrusion 1314 in the second configuration is configured to grasp or pierce the mucosal portion surrounded by the band 1312. The protrusion 1314 in the second configuration serves as an anchor and helps to keep the band 1312 set on the mucosal portion, thereby preventing the band 1312 from shifting prematurely. Other band surface structural features can be incorporated into the band to increase the roughness of the band surface and prevent it from slipping off the mucosa prematurely.

[0165] Fig. 13BA cutting member or band 1322 according to other embodiments of the present specification is shown, wherein a plurality of protrusions 1324 extend toward the center of the band in an expanded configuration and a contracted configuration. In an embodiment, the protrusions 1324 are part of the band 1322 and are positioned along the inner circumference of the band 1322, extending from the band and toward the center of the band. The band 1322 in the first configuration depicted in view 1328 is stretched to be disposed on the cap of the endoscopic device. The band 1322 in the first configuration is a circular shape having a first diameter. In an embodiment, the protrusions 1324 in the first configuration are conical, having a distal end 1326 of a tip and having a first base diameter and a first height. In an embodiment, the band 1322 includes one to ten protrusions 1324. In one embodiment, the band 1322 includes four protrusions 1324. After deployment, the band 1322 in the first configuration in view 1328 changes to the second configuration depicted in view 1330. The elastic properties of the band 1322 in the second configuration cause it to contract. The band 1322 in the second configuration has a circular shape and a second diameter. In an embodiment, the second diameter is less than the first diameter. In an embodiment, the protrusion 1324 in the second configuration is a cone with a second base diameter and a second height. In an embodiment, the second base diameter is less than the first base diameter and the second height is greater than the first height. The protrusion 1324 in the second configuration is configured to grasp or pierce the mucosal portion surrounded by the band 1312. The protrusion 1324 in the second configuration serves as an anchor and helps to keep the band 1322 set on the mucosal portion, thereby preventing the band 1322 from being displaced prematurely. In another embodiment, the grooves on the surface of the band increase its anchoring ability and prevent premature displacement.

[0166] Fig.14A The distal end 1402 of an endoscope 1404 including a cylindrical cap 1406 is shown, wherein at least two cutting members or elastic bands 1412 are positioned around the outer surface of the cap 1406 according to some embodiments of the present specification. In an embodiment, one or more elastic bands 1412 are positioned around the cap 1406 before the bands are deployed to cut mucosal tissue. Prior to deploying the bands 1412, anchors 1414, such as coils having multiple spikes or a single spike made of a shape memory material (e.g., nitinol), are aligned along the length of the bands 1412. Each band 1412 has a corresponding set of anchors 1414 positioned thereon. Fig. 14B Shows Fig.14A The device is shown in Figure 1412 of a device deployed around the base of the foregut mucosal portion 1403. After deployment, anchors 1414 are deployed inwardly toward the center of the band to grasp or pierce the mucosal portion 1403, thereby enabling anchoring into the mucosal tissue. Blood flow to the mucosal and submucosal tissue 1403 is cut off, and over a period of time, the mucosal and submucosal portions of the intestine undergo ischemic necrosis and fall off.

[0167] In general, preferably, the above-mentioned cut-out part or band is made of a first material and the anchor is made of a second material, wherein the first material is different from the second material. More preferably, the first material has a greater elasticity than the second material, and / or the first material has a Shore durometer value that is smaller than the Shore durometer value of the second material. More preferably, if the circular band is cut and arranged linearly, its entire length is equal to the first value, and if the anchor is similarly cut and / or arranged, its entire length is equal to the second value, wherein the second value is greater than the first value. More preferably, a portion of the anchor is physically attached or embedded in the band, wherein the length of the portion is equal to or less than 70% of the entire length of the anchor, preferably equal to or less than 50%, more preferably equal to or less than 25%. More preferably, the unstretched band has a diameter equal to the first value, and the anchor has one or more protrusions extending from the inner surface of the band, wherein each protrusion extends into the area surrounded by the band at a distance, and wherein the distance is equal to at least 5% of the diameter, at least 10% of the diameter, at least 20% of the diameter, at least 30% of the diameter, at least 40% of the diameter, at least 50% of the diameter, at least 60% of the diameter, at least 70% of the diameter, at least 80% of the diameter, or at least 90% of the diameter. More preferably, the unstretched band has a diameter equal to the first value, and the anchor has one or more protrusions extending from the inner surface of the band, wherein each protrusion extends into the area surrounded by the band at a distance, and wherein the distance is equal to no more than 50% of the diameter, no more than 40% of the diameter, no more than 30% of the diameter, no more than 20% of the diameter, no more than 10% of the diameter, or no more than 5% of the diameter. The band may be divided into two equal halves, wherein the anchor comprises two protrusions, wherein each of the two protrusions is located at the center of each of the two halves and extends from each of the two halves. The band may be divided into three equal thirds, wherein the anchor comprises three protrusions, wherein each of the three protrusions is located at the center of each of the thirds and extends from each of the thirds. The band may be divided into four equal quarters, wherein the anchor comprises four protrusions, wherein each of the four protrusions is located at the center of each of the quarters and extends from each of the quarters. The band may be divided into five equal fifths, wherein the anchor comprises five protrusions, wherein each of the five protrusions is located at the center of each of the fifths and extends from each of the fifths. The band may be divided into six equal sixths, wherein the anchor comprises six protrusions, wherein each of the six protrusions is located at the center of each of the sixths and extends from each of the sixths.The band may be divided into seven equal seventh portions, wherein the anchor comprises seven protrusions, wherein each of the seven protrusions is located at the center of each of the seventh portions and extends from each of the seventh portions. The band may be divided into eight equal eighth portions, wherein the anchor comprises eight protrusions, wherein each of the eight protrusions is located at the center of each of the eighth portions and extends from each of the eighth portions. The band may be divided into nine equal ninth portions, wherein the anchor comprises nine protrusions, wherein each of the nine protrusions is located at the center of each of the ninth portions and extends from each of the ninth portions. The band may be divided into ten equal tenth portions, wherein the anchor comprises ten protrusions, wherein each of the ten protrusions is located at the center of each of the tenth portions and extends from each of the tenth portions.

[0168] In various embodiments, more than 5 discrete and less than 100 discrete excision components or elastic bands are applied to the foregut mucosa and remain in place to excise the foregut mucosa or submucosa over a period of time using ischemic necrosis of the mucosa. In some embodiments, the band is deployed and remains in place for about 7 days. In some embodiments, the band is deployed and remains in place for about 1 day. In another embodiment, the band is deployed and remains in place for about 30 days. In most embodiments, after the ischemic necrosis process is complete, the band falls off without the need for additional intervention and is naturally discharged from the human body.

[0169] In other embodiments, more than 5 discrete and less than 100 discrete resection members or bands are applied to the foregut mucosa and the foregut mucosa or submucosa is resected using a hot or cold snare resection or band resection technique during endoscopic surgery. In yet another embodiment, more than 5 discrete and less than 100 discrete areas of the foregut mucosa and foregut mucosa or submucosa are resected using a cap-assisted hot or cold snare resection technique during endoscopic surgery.

[0170] In yet another embodiment, the periampullary mucosa or submucosa of the duodenum is resected without resecting the ampullary mucosa during surgery using a cap-assisted hot or cold snare or band resection technique.

[0171] In yet another embodiment, the foregut mucosa and / or submucosa is resected using an endoscopic submucosal dissection technique, wherein the foregut mucosa and / or submucosa is resected in one or more non-contiguous portions, wherein the cumulative surface area of ​​the resected mucosa is within 5 cm 2 Up to 100cm 2 between.

[0172] In one embodiment, 5 cm 2 Up to 500cm 2In another embodiment, multiple resection members or bands and corresponding anchoring structures are used to resect non-contiguous portions of the foregut mucosa. In the example of non-contiguous resection, a single mucosal resection area is less than 5 cm 2 , and the cumulative mucosal resection area can be greater than 10 cm 2 . In another embodiment, less than 50% of the continuous circumferential mucosa is resected, while greater than 50% of the non-continuous circumferential mucosa is resected. In another embodiment, a continuous length of less than 5 cm of foregut mucosa is resected, while a cumulative length of greater than 5 cm of foregut mucosa is resected. In yet another embodiment, the resection is performed in two or more discrete portions of the foregut mucosa or submucosa, wherein the resected mucosa or submucosa is intervened by one or more portions of unresected mucosa or submucosa. In some embodiments, the intervening unligated and / or resected mucosa may be treated with different ablations or electroporations or morcellation techniques to maximize the surface area treated.

[0173] FIG. 15A to FIG. 15C FIG. 15d shows a method of using an apparatus including an endoscope with a cutting tool in a series of steps to achieve morcellation for removing resected tissue from the duodenal mucosa and / or submucosal surface according to some embodiments of the present specification. FIG. 15A to FIG. 15C A top perspective view 1502d, a side view 1504d, and a top view 1506d of a rotating cutting blade 1516 for use with a cutting tool. Fig.15E is a diagram showing the use of some embodiments according to the present specification FIG. 15A to FIG. 15D A flowchart of a set of exemplary steps for implementing fragmentation in accordance with an embodiment of the present invention.

[0174] Also refer to FIG. 15A to FIG. 15E, insert the endoscope 1500 so that the distal end 1508 of the endoscope and the attached cap 1506 are located proximal to the surface of the resected tissue 1502. The intestinal tissue 1502 to be resected is resected using one of the multiple embodiments of the resection device described herein, which causes the tissue 1502 to protrude outward from the intestinal tissue surface 1504. However, the tissue 1502 to be resected can still be attached to the intestinal tissue surface 1504 at the site 1510. The rotating cutting blade 1516 as part of the cap 1506 is positioned to surround the site 1510. The endoscope 1500 includes an elongated cylindrical cap 1506 attached to the distal end 1508 of the endoscope 1500. In some embodiments, the cap 1506 is made of a transparent material. In an embodiment, the cap 1506 includes a transparent material, such as polycarbonate, polyvinyl chloride (PVC), silicone, or any other similar material, and has a diameter in the range of 5 mm to 25 mm and a total length in the range of 5 mm to 25 mm. The endoscope 1500 is positioned so that the distal rounded end of the cap 1506 is positioned to surround the site 1510 to be resected, thereby causing the target tissue 1502 to be enclosed within the cap 1506. A grasping tool 1512 is inserted through the lumen within the endoscope 1500 so as to be able to exit the distal end of the tool 1512 through the distal end 1508 of the endoscope 1500. The tool 1512 further extends through the elongated cap 1506. A pair of grasping claws 1514 are attached to the distal end of the tool 1512. In some embodiments, the grasping claws 1514 include two linear arms with rectangular surfaces, each arm including an inner surface facing the other arm and an outer surface opposite to the inner surface. Each inner surface of each arm may include a corrugated surface to allow friction and / or grasping while grasping the proximal side of the ligature tissue 1502 with the arm. At step 1552 , the rotary cutting blade 1516 is positioned proximal to the resection site 1510 , and the jaws 1514 are positioned to grasp the proximal side of the ligature tissue with the arms of the jaws 1514 .

[0175] At step 1554, and if Fig.15A As shown, the rotary cutting blade 1516 is rotated to cut at the location 1510 while applying a first force (F Pull) to pull the tool 1512 and the attached claw 1514, which has a grip proximal to the excised tissue 1502, through the lumen of the endoscopic device 1500 in a proximal direction. In some embodiments, the cutting blade 1516 is rotated to cut the tissue. In other embodiments, the gripping tool 1512 is rotated to move the tissue relative to the cutting blade 1516 to cut the tissue. In other embodiments, the cutting blade 1516 and the gripping tool 1512 are rotated simultaneously to cut the tissue. In an embodiment, the applied force is manually applied by the user. In other embodiments, the force is mechanically or automatically applied by a robotic system. In other embodiments, the force is applied by any combination of manual application by the user and mechanical / automatic application by the robotic system. The rotating cutting blade 1516 has two parts: a ring 1518 having an inner surface with a diameter of 5mm to 25mm and an outer surface with a diameter of 5mm to 25mm, and a series of equally spaced cutting blades 1520 positioned on the inner surface. The blades 1520 may include a triangular structure, with one base of each triangle attached to the inner surface of the ring 1518 and the top side opposite the base pointing to the center of the ring 1518. In some embodiments, each blade has a length or distance ranging from 1 mm to 10 mm at the base, and a height ranging from 1 mm to 5 mm. In some embodiments, each blade has a length or distance of 5 mm or less and a height of 2 mm at the base. In an embodiment, each blade 1520 is configured to be at an angle to the inner surface of the ring 1518 so that when the ring 1518 is viewed from the top side, all blades 1520 are oriented in a clockwise or counterclockwise direction. Other blade configurations known in the art may also be used in this embodiment.

[0176] At step 1556, and if Fig. 15B The second rotational force (F) is applied by tool 1512. T ) and thus, by means of the claw 1514 attached to the tool 1512 and grasping the excised tissue 1502, the excised tissue 1502 is twisted within the cap 1506. In addition to the first force F previously applied Pull In addition, a second force F is applied T At step 1558, the rotating cutting blade 1516 is simultaneously actuated (the first force F Pull and the second force F T ), resection is achieved by breaking and then separating the tissue 1502 to be resected from the intestinal tissue surface 1504 from the proximal portion of the resection site 1510. Fig. 15CEndoscope 1500 is depicted at the end of morcellation, wherein intestinal tissue 1502 is cut within cap 1506, according to some embodiments of the present specification. The resected and separated tissue piece 1502 is then pulled out by tool 1512 through the proximal side of the lumen of endoscopic device 1500. In some embodiments, cutting blade 1516 is fixed and the rotational motion is provided by tool 1512. The motion of cutting blade 1516 or tool 1512 can be vibrating or oscillating. Also refer to FIG. 15A to FIG. 15C ,exist Fig.15A In the process, morcellation begins, wherein the tissue is pulled to (by F pull The cap (or morcellating tube) 1506 is inserted into the morcellating tube and the tissue strips are cut appropriately. Fig. 15B In the case of shredding the tissue strip, the strip has a length that causes the strip to twist within the cap 1506. This creates a tissue mass torque (FT) caused by the rotating cutting blades that causes the tissue to rotate. Fig. 15C In FIG. 5 , the tissue piece is free to follow the torque FT and break away from the cap (force Fz), thereby generating a combined force vector Fc that indicates the direction in which the tissue piece falls or is thrown away.

[0177] Embodiments of the present description may be used to treat at least one of overweight, obesity, eating disorders, metabolic syndrome, dyslipidemia, diabetes, polycystic ovary disease, fatty liver, non-alcoholic fatty liver disease, or non-alcoholic steatohepatitis by using foregut mucosal and / or submucosa resection and / or dissecting system to resect foregut tissue.

[0178] In various embodiments, resection treatment is provided to achieve treatment goals or endpoints for patients with obesity, overweight, eating disorders, dyslipidemia, or diabetes, and the first treatment phase for these patients is considered successful if any one or more of the following treatment goals or endpoints are achieved: the patient's total body weight is reduced by at least 1% relative to the patient's total body weight before resection; the patient's excess body weight is reduced by at least 1% relative to the patient's excess body weight before resection; the patient's total body weight is reduced by at least 1% relative to the patient's total body weight before resection, and the patient's fitness level is reduced by no more than 5% relative to the patient's fitness level before resection; the patient's excess body weight is reduced by at least 1% relative to the patient's excess body weight before resection, and the patient's fitness level is reduced by no more than 5% relative to the patient's fitness level before resection; the patient's pre-meal ghrelin level is reduced by at least 1% relative to the patient's pre-meal ghrelin level before resection; the patient's post-meal ghrelin level is reduced by at least 1% relative to the patient's post-meal ghrelin level before resection; the patient's post-meal ghrelin level is reduced by at least 1% relative to the patient's pre-meal ghrelin level before resection; the patient's post-meal ghrelin level is reduced by at least 1% relative to the patient's the patient's motor output is increased by at least 1%; the patient's glucagon-like peptide-1 level is increased by at least 1% relative to the patient's level before resection; the patient's leptin level is increased by at least 1% relative to the patient's level before resection; the patient's appetite is reduced over a predetermined period of time relative to the patient's appetite before resection; the patient's peptide YY level is increased by at least 1% relative to the patient's level before resection; the patient's lipopolysaccharide level is reduced by at least 1% relative to the patient's level before resection; the patient's motilin-related peptide level is reduced by at least 1% relative to the patient's level before resection; the patient's cholecystokinin level is increased by at least 1% relative to the patient's level before resection; the patient's resting metabolic rate is increased by at least 1% relative to the patient's resting metabolic rate before resection; the patient's plasma beta-endorphin level is increased by at least 1% relative to the patient's level before resection; the patient's HbA1c level is reduced by at least 0.3%; the patient's triglyceride level is reduced by at least 1% relative to the patient's triglyceride level before resection; the patient's total blood cholesterol level is reduced by at least 1% relative to the patient's total blood cholesterol level before resection; the patient's blood glucose level is reduced by at least 1% relative to the patient's blood glucose level before resection; the composition of the human's intestinal flora is adjusted from a first state before resection to a second state after resection, wherein the first state has a first level of bacteroidetes and a first level of firmicutes, wherein the second state has a second level of bacteroidetes and a second level of firmicutes, wherein the second level of bacteroidetes is at least 3% more than the first level of bacteroidetes, and the second level of firmicutes is at least 3% less than the first level of firmicutes; or, the patient's daily cumulative dose of an antidiabetic drug is reduced by at least 10% relative to the patient's daily cumulative dose of an antidiabetic drug before resection. In most embodiments, the incidence of severe hypoglycemia is reduced to <1%. .

[0179] In various embodiments, resection treatment is provided to achieve the following treatment goals or end points for patients with dyslipidemia, and the first phase of treatment for these patients is considered successful if any one or more of the following treatment goals or targets are achieved: the patient's lipid profile is improved by at least 10% relative to the patient's lipid profile before resection, wherein the lipid profile is defined at least by the ratio of LDL cholesterol to HDL cholesterol, and the improvement is defined as a decrease in the ratio of LDL cholesterol to HDL cholesterol; the patient's LDL cholesterol level is reduced by at least 10% relative to the patient's LDL cholesterol level before resection; or, the patient's VLDL cholesterol level is reduced by at least 10% relative to the patient's VLDL cholesterol level before resection.

[0180] In various embodiments, resection therapy is provided to achieve the following treatment goals or end points for patients with nonalcoholic steatohepatitis (NASH) or nonalcoholic fatty liver disease (NAFLD), and a first treatment phase for these patients is considered successful if any one or more of the following treatment goals or end points are achieved: ALT or AST levels are reduced by at least 10% relative to ALT or AST levels before resection; serum ferritin levels are improved by at least 10% or less than 1.The following criteria were considered: absolute serum ferritin level of 5ULN (upper limit of normal); an improvement in hepatic steatosis (HS) level of at least 5% or less than 5% relative to the pre-resection HS level, as measured by magnetic resonance (MR) imaging, or by spectroscopy or proton density fat fraction; an improvement in the NAFLD fibrosis score (NFS) of at least 5% relative to the pre-resection NAFLD activity score (NAS) of at least 5% relative to the pre-resection NAS; an improvement in the SAF score of at least 5% relative to the pre-resection steatosis active fibrosis (SAF) score; a decrease in the annual average fibrosis progression rate of at least 5% relative to the pre-resection average fibrosis progression rate, and an increase in the annual average fibrosis progression rate of at least 5% relative to the pre-resection average fibrosis progression rate Progression rate was measured by histology, Fibrosis-4 (FIB-4) index, aspartate aminotransferase (AST) to platelet ratio index (APRI), serum biomarkers (enhanced liver fibrosis (ELF) panel, fibrometer, FibroTest, or Hepascore), or imaging (transient elastography (TE), magnetic resonance elastography (MRE), acoustic radiation force impulse imaging, or ultrasound shear wave elastography); at least a 5% decrease in circulating levels of cytokeratin-18 fragments relative to pre-resection levels; and a decrease in circulating levels of cytokeratin-18 fragments relative to pre-resection FIB-4 index. The FIB-4 index, aspartate aminotransferase (AST) to platelet ratio index (APRI), serum biomarkers (enhanced liver fibrosis (ELF) group, fiber meter, Phibroe test or Hepa score), or imaging methods (transient elastography (TE), magnetic resonance elastography (MRE), acoustic radiation force impulse imaging or ultrasound shear wave elastography), the FIB-4 index, aspartate aminotransferase (AST) to platelet ratio index (APRI), serum biomarkers (enhanced liver fibrosis (ELF) group, fiber meter, Phibroe test or Hepa score), or imaging methods (transient elastography (TE), magnetic resonance elastography (MRE), acoustic radiation force impulse imaging or ultrasound shear wave elastography) at least a 5% improvement in liver stiffness (force pulse imaging or ultrasound shear wave elastography); at least a 5% decrease in liver stiffness relative to pre-resection liver stiffness as measured by vibration-controlled transient elastography (VCTE / FibroScan); at least a 2-point improvement in NAS, at least a 1-point improvement in hepatocyte swelling, at least a 1-point improvement in lobular inflammation or steatosis, and no increase in fibrosis score relative to pre-resection NAS, hepatocyte swelling, lobular inflammation, steatosis, and fibrosis scores; at least a 5% improvement in NFS score relative to pre-resection NFS score; or at least a 5% improvement in any of the above listed NAFLD parameters compared to sham intervention or placebo.

[0181] In various embodiments, ablation therapy is provided to achieve the following treatment goals or end points for diabetic patients, and the first phase of treatment for these patients is considered successful if any one or more of the following treatment goals or end points are achieved: a 20% reduction in the dose of an oral antidiabetic drug (OAD) or at least one of a reduction in the dose of an OAD in at least 20% of the patients.

[0182] In various embodiments, ablation therapy is provided to achieve the following treatment goals or end points for diabetic patients, and the first phase of treatment for these patients is considered successful if any one or more of the following treatment goals or end points are achieved: at least one of a 20% reduction in insulin dose or a reduction in insulin dose in at least 20% of patients, or preventing progression from OAD to insulin therapy in at least 10% of patients.

[0183] In various embodiments, resection therapy is provided to achieve the following treatment goals or end points for diabetic patients, and the first treatment phase for these patients is considered successful if any one or more of the following treatment goals or end points are achieved: at least one of a 5% reduction in the incidence of severe hypoglycemic events or a reduction in the incidence of severe hyperglycemic events in at least 25% of the patients.

[0184] If any of the above treatment goals or end points are met, treatment is completed and no further resections are performed. If any of the above treatment goals or end points are not met, the entire resection procedure and assessments can be repeated in the second treatment phase and subsequent treatment phases, except for the screening process. If the treatment goals or end points are still not met, the patient can wait at least 4 weeks between each resection procedure and each assessment.

[0185] The above examples are merely examples of many applications of the system of this specification. Although only a few embodiments of the present invention are described herein, it should be understood that the present invention may be implemented in many other specific forms without departing from the spirit or scope of the present invention. Therefore, the present examples and embodiments are considered to be illustrative rather than restrictive, and the present invention may be modified within the scope of the appended claims.

Claims

1. A device for removing body tissue, comprising: a cap configured to be attached to a distal end of an endoscope, wherein the cap includes a central lumen; a suction source configured to apply negative pressure through the central lumen of the cap; and At least one cutting member positioned around an outer surface of the cap, wherein the at least one cutting member has an inner surface including at least one anchor, wherein the at least one cutting member includes a first material, the at least one anchor includes a second material, and wherein the first material is different from the second material, wherein the at least one cutting member is configured to change from a first configuration when positioned on the cap to a second configuration once deployed, wherein in the second configuration, the at least one cutting member is configured to surround a portion of the body tissue and the at least one anchor contacts the tissue to secure the cutting member to shrink the tissue and reduce blood flow to the tissue.

2. The device according to claim 1, wherein: The at least one cut-out component comprises a band, a ring, an O-ring, an elastic circle or any other component adapted to have a first configuration having a circumference M when subjected to pressure and adapted to automatically transition to a second configuration having a circumference N when the pressure is removed, wherein N is less than M.

3. The device according to claim 1, wherein: The anchor comprises a wire of shape memory material having at least one first portion extending into the at least one cut-out feature and at least one second portion extending out of the at least one cut-out feature and toward a center of the at least one cut-out feature.

4. The device according to claim 3, wherein: The shape memory material includes Nitinol.

5. The device according to claim 3, wherein: In the second configuration, the at least one second portion of the wire is configured to anchor into the body tissue.

6. The device according to claim 3, wherein: In the second configuration, the at least one second portion of the wire is spike-shaped and is configured to penetrate the body tissue.

7. The device of claim 1, comprising 1 to 10 cutting elements.

8. The device of claim 1 further comprising a conduit extending between the cap and the suction source.

9. A method for removing body tissue from a patient, comprising: A device is provided that is configured to be passed through an endoscope, the device comprising: a cap positioned on a distal end of the device, wherein the cap includes a central lumen; and at least one cutting member positioned about an outer surface of the cap, wherein the at least one cutting member has an inner surface including at least one anchor, wherein the at least one cutting member is configured to change from a first configuration when positioned on the cap to a second configuration once the cap is deployed, wherein when in the second configuration, the at least one cutting member is configured to surround a portion of the body tissue and anchor into the tissue with the anchor to shrink the tissue and reduce blood flow to the tissue; inserting the device into the patient through the endoscope and advancing the device so that the distal end of the device is positioned in the patient's gastrointestinal tract; activating a suction source to apply negative pressure through the central lumen of the cap; drawing a portion of the body tissue into the central lumen of the cap, wherein the portion comprises at least 1 square centimeter of body tissue; deploying the at least one cutting member from the device around a base of the body tissue; removing the device from the patient; The at least one cutting member is maintained about the body tissue and cuts off blood flow to the body tissue.

10. The method according to claim 9, wherein: The at least one cut-out component comprises a band, a ring, an O-ring, an elastic circle or any other component adapted to have a first configuration with a circumference M when subjected to pressure and adapted to automatically transition to a second configuration with a circumference N when the pressure is removed, wherein N is less than M.

11. The method according to claim 9, wherein: The anchor comprises a wire of shape memory material having at least one first portion extending into the at least one cut-out feature and at least one second portion extending out of the at least one cut-out feature and toward a center of the at least one cut-out feature.

12. The method according to claim 11, wherein: The shape memory material includes Nitinol.

13. The method according to claim 11, wherein: In the second configuration, the at least one second portion of the wire is configured to anchor into the body tissue.

14. The method according to claim 11, wherein: In the second configuration, the at least one second portion of the wire is spike-shaped and is configured to penetrate the body tissue.

15. The method according to claim 9, wherein: The device comprises from 1 to 10 cutting elements.

16. The method according to claim 9, wherein: The device also includes a conduit extending between the cap and the suction source.

17. The method of claim 9, for treating at least one of overweight, obesity, eating disorders, metabolic syndrome, dyslipidemia, diabetes, polycystic ovary disease, fatty liver, non-alcoholic fatty liver disease, or non-alcoholic steatohepatitis.

18. The method according to claim 9, further comprising: The treatment end point was determined after resection.

19. The method according to claim 18, wherein: The treatment endpoint is a reduction of at least 1% in the total body weight of the patient relative to the total body weight of the patient before resection; a reduction of at least 1% in the excess body weight of the patient relative to the excess body weight of the patient before resection; The patient's total weight is reduced by at least 1% relative to the patient's total weight before resection, and the patient's fitness level is reduced by no more than 5% relative to the patient's fitness level before resection; the patient's excess weight is reduced by at least 1% relative to the patient's excess weight before resection, and the patient's fitness level is reduced by no more than 5% relative to the patient's fitness level before resection; the patient's pre-meal grelin level is reduced by at least 1% relative to the patient's pre-meal grelin level before resection; the patient's post-meal grelin level is reduced by at least 1% relative to the patient's post-meal grelin level before resection; or the patient's exercise output is increased by at least 1% relative to the patient's exercise output before resection.

20. The method according to claim 18, wherein: The treatment endpoint is an increase of at least 1% in the patient's glucagon-like peptide-1 level relative to the patient's level before resection; an increase of at least 1% in the patient's leptin level relative to the patient's level before resection; a decrease in the patient's appetite over a predetermined period of time relative to the patient's appetite before resection; an increase of at least 1% in the patient's peptide YY level relative to the patient's level before resection; a decrease of at least 1% in the patient's lipopolysaccharide level relative to the patient's level before resection; a decrease of at least 1% in the patient's motilin-related peptide level relative to the patient's level before resection; At least one of an increase in the patient's cholecystokinin level by at least 1% relative to the patient's cholecystokinin level before resection; an increase in the patient's resting metabolic rate by at least 1% relative to the patient's resting metabolic rate before resection; an increase in the patient's plasma beta-endorphin level by at least 1% relative to the patient's plasma beta-endorphin level before resection; a decrease in the patient's HbA1c level by at least 0.3% relative to the patient's HbA1c level before resection; a decrease in the patient's triglyceride level by at least 1% relative to the patient's triglyceride level before resection; a decrease in the patient's total blood cholesterol level by at least 1% relative to the patient's total blood cholesterol level before resection; or a decrease in the patient's blood glucose level by at least 1% relative to the patient's blood glucose level before resection.

21. The method according to claim 18, wherein: The treatment endpoint is a reduction of at least 10% in the patient's daily cumulative dose of antidiabetic drugs relative to the patient's daily cumulative dose of antidiabetic drugs before resection; or elimination of 10% of one or more antidiabetic drugs used by the patient before resection.

22. The method according to claim 18, wherein: The treatment endpoint is a 10% decrease in ALT or AST level relative to the pre-resection level; an improvement of at least 10% in serum ferritin level relative to the pre-resection level or an absolute serum ferritin level below 1.5 ULN (upper limit of normal); an improvement of at least 5% or less than 5% in hepatic steatosis (HS) relative to the pre-resection level, wherein the HS is measured on a liver biopsy; an improvement of at least 5% or less than 5% relative to the pre-resection HS level, wherein the HS is measured by magnetic resonance (MR) imaging, or by spectroscopy or proton density fat fraction; an improvement of at least 5% in NAFLD fibrosis score (NFS) relative to the pre-resection level; an improvement of at least 5% in NAFLD activity score (NAS) relative to the pre-resection level; an improvement of at least 5% in SAF score relative to the pre-resection level; and a reduction of at least 5% in the annual average fibrosis progression rate measured by histology relative to the pre-resection level.

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