Introduction

The increasing prevalence of morbid obesity over the last few decades led the World Health Organization (WHO) to address it as global epidemic [1]. At the same time, the growing interest in obesity treatment resulted in the rapid development of new technologies and procedures across the globe. Currently, surgery provides the most reliable and effective treatment for morbid obesity.

Results of bariatric surgery can be evaluated with EWL (Excess Weight Loss, typically ranging from 47.5 to 70.1%) [2], or with resolution or significant improvement of comorbidities such as type II diabetes, dyslipidemia, hypertension, sleep apnea, and metabolic syndrome in general. The incidence of obesity-related comorbidities assessed 10 years after surgery is significantly reduced, in comparison with that of patients treated with non-surgical therapy [3]. Minimally invasive surgery (MIS) is currently the gold standard for treatment of morbid obesity, with significant reduction in complication rates and postoperative recovery when compared to traditional “open” techniques [4]. As today, more than 95% of surgeries are performed by laparoscopy, and most frequent procedures are sleeve gastrectomy, Roux-en-Y gastric bypass, one-anastomosis gastric bypass, adjustable gastric banding, and others.

However, the constant strive for innovation and the persistent efforts to deliver better results with less invasive techniques have also led to development of wide variety of additional MIS and endoluminal techniques.

Endoscopic bariatric procedures and other new minimally invasive technologies represent a trending topics nowadays. Bariatric surgeons are constantly flooded with new techniques and devices, supported by an increasing number of low-quality scientific publications, often sponsored by manufacturing companies.

The relative market is also very fluid and many companies rebranded their products several times in the past years, some declared insolvency while others retired their products, contributing to literature fragmentation and great confusion for the surgeon. Most of the current literature also fails to provide a comprehensive view on the subject, often lacks supportive data and, sometimes, is even influenced by media hype.

Whit the aim of giving new visual angles and perspective, this manuscript is conceived to provide a comprehensive overview of all the most recent endoluminal and minimally invasive bariatric surgical devices, including the most important ones that are no longer available on the market or no longer in development. Although it increased the length of our manuscript, we provided (where available) the development history of each device because we feel that it is of key importance for the reader to understand the originating idea and each single step that lead to a successful or flawed technique.

As said, although in experimental settings many devices attempted to reproduce the results of conventional surgical modalities, only a few of them have reached the clinical field, after passing both safety and efficacy tests.

This is why an open-minded but cautious approach to novelties is a must: enthusiasm is frequently accompanying these alternative options (especially driven by the innovation’s proponents….).

By presenting the data for each device, we also want to highlight the difficulty in comparing their efficacy, due to the different scales and parameters used in the literature. This may help the surgical community to find new fixes and improvements to currently available devices, while stimulating higher quality research on this topic.

We decided to include in this review the devices based on electric pacing/neuromodulation, as their mechanism of action is totally alternative to “classic” laparoscopic procedures, although their placement requires a surgical approach.

Intragastric balloons are not described, being temporary devices; single incision and NOTES techniques were not considered as well, representing only an alternative “through the wall” route, but not allowing the execution of different procedures.

We then tried to classify this innovative devices and procedures within the same framework of the “classic” laparoscopic ones (Table 1).

Table 1 Minimally invasive technologies in morbid obesity treatment
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A good alternative to our choice is represented by the division of techniques in 3 groups, as proposed by E. Mathus-Vliegen [5]. We partially modified it and reclassified our paragraphs according to, as seen in Table 2.

Table 2 Endoscopic bariatric and metabolic therapies
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Materials and Methods

We searched PubMed, Embase, Cochrane, Google Scholar, USPTO, and EPO for articles, clinical trials, and patents relating to the endoscopic management of obesity, as said excluding intragastric balloons.

Discussion on single devices/procedures is exploited in their own paragraph, while a more general, perspective overview is given in the “Discussion” chapter.

Results

Seventy-seven articles were selected and incorporated in the manuscript. The following review of the techniques includes electrical pacing/modulation and vagal blocking, endoluminal treatments, gastric restrictive procedures, derivative procedures, and transluminal treatments.

Procedures

Electrical Pacing/Modulation and Vagal Blocking

Currently, there are two different electrical pacing devices that achieve notable results for the treatment of morbid obesity: the gastric pacing and the intraabdominal vagal blocking.

Implantable Gastric Stimulator

The concept of treating obesity by using selective autonomic activation via electrical pacing was introduced by Cigaina (1996) [6] and later reintroduced as Implantable Gastric Stimulator® (IGS®-Transcend®). This gastric pacemaker stimulates the vagal innervation of the stomach through a lead wire implanted within the wall of the stomach [7]. The lead is placed laparoscopically on the lesser curvature—6 cm from the pylorus and is fixed distally with clips in order to prevent dislodgment. The pace generator is connected to the lead and subsequently positioned above the fascia. During the operation, the gastric mucosa is monitored by gastroscopy in order to prevent inadvertent needle perforation into the gastric lumen [8]. Preliminary studies were encouraging, as the mean EWL in a cohort of 103 morbidly obese subjects was 10.3% at 12 months. Thirty-four of these patients were followed for over 29 months and showed a 20% EWL [9]. The non-randomized multicenter trial “Laparoscopic Obesity Stimulation Study” (LOSS) trial involved a total of 69 patients, and reported a mean % EWL at 6 months of 17.8 (n = 51), which increased to 21.0 at 10 months (n = 43), and stabilized to 21.0 at 15 months (n = 20) [8, 10]. But, when prospective, randomized trials are attempted, results seem different: in fact, a more recent trial known as the SHAPE Trial demonstrated poor results when compared to placebo. The SHAPE Trial was a prospective, randomized, placebo-controlled, double-blind, multicenter study that enrolled a total of 190 patients. All the subjects were put on a diet with a 500 kcal/day deficit (and this is controversial, or even a bias, as does not mimic normal eating behavior) and divided into 2 groups: the treatment group (with the activated device) and the control group (device not activated). The study showed no significant difference between the two groups in terms of % EWL, as the control group lost 11.7% ± 16.9% of excess weight and the treatment group lost 11.8% ± 17.6% (P = .717) [11]. After these initial experiences, the concept of pacing evolved to that of neuromodulation, so that three new devices are currently being tested: the Diamond System®, the Abiliti System®, and the VBLOC® therapy.

Diamond

The Diamond (TANTALUS) System® (MetaCure, Inc.) is a meal-activated implantable system that delivers gastric contractility modulation signals. Gastric contractility modulation is delivered for 75 min starting at meal detection. The pulse is applied 15 min “on” and 15 min “off “for the 75 min of activity [12]. These electrical signals are synchronized with the intrinsic electrical activity of the stomach and have been shown to enhance the force of antral contractions, increasing afferent signaling of the vagus nerve without interfering with the intrinsic gastric electrical rhythm [13]. The implantation procedure is performed by laparoscopy and controlled by intraoperative gastroscopy. Three bipolar leads are implanted in the muscular layer of the stomach and then connected to an implantable pulse generator located in a subcutaneous pocket [14]. Although limited by the relatively small numerical dimension, the results from the first trials showed improvements in metabolic conditions: on the lipid profile, a decrease from enrollment to 6 months levels in total cholesterol (196 ± 27 mg/dl vs. 164 ± 31 mg/dl p < .05) and LDL cholesterol (125 ± 26 mg/dl vs. 103 ± 28 mg/dl p < .05); sustained decrease of blood pressure levels occurred from 124 ± 12 mmHg to 112 ± 10 mmHg at 6 months p < .05 as well as sustained weight loss from 107.7 ± 21.1 kg to 102.4 ± 20.5 kg at 6 months p < .05 [15] and EWL of 30.5 ± 8.5 kg at 1 year p < .05 [16, 17]. The only adverse events described are discomfort or pain in the pocket area, dyspepsia, and lead dislodgment, present during the follow-up. Unfortunately, the use of kg weight loss makes comparison to other devices difficult.

Diamond is a device more suitable to treat diabetes and improve glycemic control than obesity itself. Its effects of decreasing body weight and lowering systolic blood pressure are only marginal. Improvements in glycemic control in patients with type 2 diabetes were confirmed in a recent cross-over study. The study compared the effects of the implanted device that is turned on to the implanted device that is turned off on HbA1c levels in inadequately controlled patients with type 2 diabetes. The change in HbA1c from baseline to 48 weeks in which the electrical signal was turned on for the last 24 weeks was significantly decreased (8.40 ± 0.15%; 68 ± 1.21 mmol/mol to 7.47 ± 0.15%; 58 ± 1.16 mmol/mol, p = 0.001) [12]. Currently MetaCure stopped the production of the device and is discontinuing customer support of the Diamond recommending its removal.

Abiliti

The Abiliti System® (IntraPace, Inc.) is a laparoscopically implanted device at the lesser curvature of the stomach, composed by a transgastric sensor which detects food and triggers the stimulator. The effect of the stimulation is believed to result in early satiety. The Abiliti System® constantly records subjects’ physical activity, using a 3D accelerometer embedded in the implanted device. The subjects are then given the possibility to download all the data through a personal website and accordingly adjust their diet and physical activity. The only published data available to date include a cohort of 60 patients divided in two clinical trials conducted separately in Germany by Horbach et al. and in Spain by Miras et al. In the German prospective, multicenter study, 34 obese subjects with a BMI of 42.1 ± 5.3 kg/m2 achieved mean EWL of 28.7% at 12 months (95%CI, 34.5 to 22.5%) with mean reduction in BMI of 4.8 ± 3.2 kg/m2. At 27 months, the EWL was 27.5% (95%CI, 21.3 to 33.7%). The device was reported to have only minor complications [18]. The Spanish trial enrolled 27 obese patients and reached EWL of 49.3 ± 19.2% at 12 months with no significant differences between gender or age sub-groups. The % EWL data were segmented into two groups according to BMI 30–40 kg/m2 patients (obesity grade I and II) and BMI > 40 kg/m2, with the results of weight loss being significantly higher for the lower BMI group (59.1 ± 19.5 vs. 46.7 ± 13.4, respectively, p < 0.01). A satisfactory safety profile was demonstrated by this trial as well [19].

VBLOC

The vagal blocking therapy (VBLOC®) is based on a different principle and induces an intermittent intraabdominal vagal blocking using high-frequency electrical currents. Two electrodes are positioned laparoscopically on the anterior and posterior vagal trunks near the esophagogastric junction (EGJ) and the neuroregulator is placed subcutaneously. In the initial version of the device, the power source was an external battery, intended to be on a belt of the patient. The first trial involved a cohort of 31 patients. No adverse events related to the device or the procedures were reported. The mean EWL at 4 weeks, 12 weeks, and 6 months after device implantation was 7.5%, 11.6%, and 14.2%, respectively. Several clinical and experimental observations hypothesized the intermittent vagal blockade to be a key factor in achieving and maintaining the desired clinical effects [20,21,22].

The first comprehensive and extensive study regarding VBLOC was the EMPOWER Study conducted in USA and Australia between 2011 and 2012. The EMPOWER was a multicenter, prospective, randomized, double-blind, controlled, parallel group trial with a 12-month post-randomization follow-up which enrolled 294 patients randomized in a treatment group of 192 patients and 102 controls. Patients in both arms underwent placement of the VBLOC but the device was not activated in the control arm. The results after 1 year of treatment showed no difference in terms of % EWL and weight loss between groups. The Authors reported that the reason of such lack of difference is likely secondary to the vagal manipulation and/or seemingly minor electrical input delivered to the vagal nerves by the switched off device in the control arm.

Other data retrieved during this study, however, show potentially beneficial effects of vagal blockade on weight loss like increased early satiety and decreased appetite in both groups. Weight loss was greater with increasing use in both groups.

In 2013, Shikora et Al. published the results of an open-label, multicenter clinical trial with a 12-month follow-up that included 28 obese type 2 DM patients implanted with the VBLOC. The results of the trial seemed favorable with a mean % EWL at 12 months 25 ± 4% (p < 0.0001) and average hours of therapy delivery per day of 14 ± 0.1 h. BMI reduction at 12 months was 3.0 ± 0.4 kg/m2. Weight loss at 12 months was 8.4 ± 1.4 kg (p < 0.0001). Metabolic implications of the therapy were also retrieved, such as HbA1c and FPG reduction at all time periods. After 12 months, 3 subjects discontinued their diabetes medication and 6 decreased the dose, while the remaining 13 had no change and 4 increased diabetes medications. Statistically significant reductions in SBP, DBP, and MAP from baseline were observed at many time points after implantation in all subjects.

Consistently with data from previous studies, the intermittent vagal blockade showed a positive effect on arterial hypertension in this study as well, achieving and maintaining blood pressure values close to normal by 1 week of treatment. Waist circumference decreased by 8 ± 1 cm, 9 ± 2 cm, and 11 ± 2 cm at 12 weeks and 6 and 12 months, respectively (p < 0.001, baseline = 120 ± 2 cm) [22, 23].

The second version of the device (FDA approved in 2015) was tested in the RECHARGE study, a prospective, randomized, double-blind, controlled, parallel group trial. The neuroregulators in both groups were programmed to deliver therapy for at least 12 h per day. The VBLOC implanted in the placebo group was totally switched off, in order to avoid the possible bias of the previous EMPOWER study. Safety of the device was confirmed with only 4.9% of the patients in the nerve blockade group needed a revision procedure to replace or reposition the neuroregulatory because of pain at the insertion site. The other main complications were heartburn and pain during therapy. Weight loss results were greater in the vagal nerve block group. At 12 months, the mean % EWL was 26.1% in the nerve block group and 16.9% in the sham group. However, the mean difference in the % EWL between groups was 8.5 percentage points (95%CI, 3.1–13.9), which did not meet the 10-point target (P = .71) of the study design.

The 6% initial body weight loss seen in the sham group in RECHARGE study was similar to the sham effect in the previous EMPOWER trial [24]. Further studies are yet to investigate the role in reducing arterial hypertension.

The results of the RECHARGE trial at 18 months were recently published by Shikora et al. and demonstrate sustained weight loss with VBLOC therapy [25].

Additional studies are needed to compare the effectiveness of vagal nerve block with other obesity treatments and to assess long-term durability of weight loss and safety. In the preliminary analysis of the very first RECHARGE study data, the authors noted that lower BMI patients may respond better to the VBLOC therapy, although no mention of this effect is present in the final results. In this regard, we feel that VBLOC therapy might be more appealing to patients with moderate or less severe obesity, compared to more invasive surgical procedures.

Endoluminal Treatment

A wide variety of endoscopic implantable devices, intended for treatment of morbid obesity, have been proposed. The following devices and concepts have achieved some level of clinical significance. It must be however stressed that the majority of them did not reach significant results and/or are not available anymore for clinical use.

TransPyloric Shuttle

The TransPyloric Shuttle (TPS) consists of a large bulb made of silicone connected to a smaller cylindrical bulb by a flexible silicone connection (Fig. 1). When positioned endoscopically, the larger bulb prevents migration from the stomach while the smaller bulb passes freely into the duodenum during normal peristalsis, allowing the device to self-orient and assumes transpyloric positioning. Then, the larger bulb engages the pylorus directly to create an intermittent seal intended to reduce the rate of gastric outflow, enabling an overall reduction in caloric intake and weight loss.

Fig. 1
figure 1

a POSE. b Aspiration therapy. c TERIS. d Full Sense. e TransPyloric Shuttle. f Magnamosis. g Incisionless Anastomotic System. h Duodenal-jejunal bypass sleeve. i Vagal blocking device. j Overstitch

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The device is delivered and removed endoscopically in standard over the tube technique. During deployment, the delivery catheter is inserted through a pre-placed overtube, and the helical coil is released into the stomach where it assumes its functional shape. The device then resides in the stomach for the desired treatment period. Removal can be easily achieved endoscopically using standard endoscopic instruments.

The rationale behind the TPS is that by slowing down gastric emptying it may enable an overall reduction in caloric intake by helping the subject feel full sooner (early satiety) and/or feel full longer (prolonged satiety/reduced hunger) [26].

To evaluate the safety and efficacy of both device and procedure, a first prospective, open-label, non-randomized, single-center trial (ENDObesity™ I Study) was conducted. Twenty subjects with mean BMI of 36.0 ± 5.4 were enrolled and assigned to 3-month and 6-month treatment cohorts. Throughout the study, surveillance endoscopies were performed to evaluate the device and the stomach condition. Primary outcomes measures included % EWL, total weight loss, and adverse events. Devices were deployed and retrieved in total of 20 patients without any complications. Mean procedure times for delivery and retrieval were 10.3 ± 3.9 min and 12.9 ± 6.4 min, respectively. Patients demonstrated minimal transient intolerance to the TransPyloric Shuttle and were able to quickly return to normal daily activity. At 3 months, the patients achieved mean % WL of 8.9 ± 5.0%, mean % EBMIL of 33.1% ± 18.7%, and mean % EWL of 25.1 ± 14.0%. At 6 months, the patients achieved mean % WL of 14.5 ± 5.8%, mean % EBMIL of 50.0 ± 26.4%, and mean % EWL of 41.0 ± 21.1%. In addition, 100% achieved at least 5% of WL and 80% achieved more than 10% WL at 6 months. Both the 3- and 6-month group patients had statistically significant improvements to the overall IWQOL-Lite score that exceeded the 7.7- to 12-point threshold to define a clinical change [27]. Two patients suffered from persistent gastric ulceration that led to the device removal approximately 1 to 2 weeks prior to their scheduled removal dates. Both patients recovered completely with no residual adverse effects. All ulcers were located in the gastric antrum and endoscopic evaluation suggested that the development of ulceration was associated with a surface feature on the device, leading to device design improvements [26]. A new randomized, double-blind trial, called the ENDObesity II Study was completed in March 2018. A total of 270 patients with BMI 30–40 kg/m2 were randomized in 2:1 ratio to TPS placement or control arm. Mean % TBL at 12 months was 9.5% (8.2–10.8%) in the TPS group compared to 2.8% (1.1–4.5%) for the control group; moreover, % EWL resulted higher in the TPS cohort than control 30.9% vs. 9.8%, respectively. In addition, BMI reduction at 12 months was significantly higher with TPS compared with controls (3.5 vs. 1.01, p < .0001). Although serious adverse events reported were 2.5% in TPS group, early removal of the device was necessary in 21 patients (10.3%) due to an adverse event and gastroduodenal ulcers occurred in 10.3% of TPS patients: none developed bleeding or perforation [28]. Results from this trial lead to the recent FDA approval for the device [26].

Absorbable Biocompatible Material Injections

Sub-esophagogastric junction injection of hyaluronic acid (HA) has been used in combination with either sleeve gastrectomy (SG) or endoscopic intragastric balloon placement. A group led by J. Dargent proposed the combination approach of SG with HA. The procedure was performed in two intraoperative steps: with the initial SG was followed by sub-mucosal, circumferential injection of the biocompatible material matching the anatomic position of a gastric band. A three-staged study called OBENDO was performed to assess the performance of the technique. For the 1st stage, the authors selected a total of 8 patients: 4 subjects represented the study group (SG + HA) and 4 controls who underwent SG only. Three complications were recorded: one in the SG + HA group and 2 in the control group. Mean BMI in the HA + SG group was 42.5 (38.6–47), and 37.5 (30–42.5) in the control; at 6 months, it was respectively 34.1 (31–36.2) and 32.2 (27–32.3).

Mean BMI loss was 19.3% (13.9–27) in the HA group, and 14% (7.8–24) in the control group [29]. The second stage of the trial (OBENDO 2) is a prospective, single-blinded, randomized and controlled multicenter study that involved 98 patients from 2010 to 2012 and was intended to compare the effects of hyaluronic acid injection, balloon, and the combination of both in a sequential mode.

Three groups were selected: group 1 (balloon alone), group 2 (balloon followed by injection at the time of removal, i.e., 6 months), group 3 (injection, and balloon placement at 6 months). Percentage weight loss at 6 months has been 8.8% in groups 1 and 2 (balloon) versus 7.4% in group 3 (hyaluronic acid injection). The study also demonstrated that the effect of the hyaluronic acid injection does not last longer than the duration of an intragastric balloon.

The same team investigated HA infiltration combined with the intragastric balloon in the subsequent OBENDO 3 trial: they evaluated 3- to 6-month interval between injection and balloon placement, in order to reinforce the results of the OBENDO 2 [30]. The results of the 101 patients recruited for the study confirmed that the procedure is safe with low complication profile. Only one major complication (i.e., hepatic abscess) occurred when HA injections were done at the time of balloon removal. BMI loss at 6 months was inferior in the HA only group (31 patients) compared with the intragastric balloon (IGB) groups (68 patients) (2.1 ± 0.4 versus 3.4 ± 0.3, p = 0.0071). The combined HA + IGB treatment effects on BMI loss was only evident at 18 months; however, the results were not statistically significant at any time point [31]. According to Dargent, the injection of a biocompatible material could also be helpful if associated with endoluminal techniques and devices which do not provide a sufficient restriction at the outlet e.g. Stomaphyx® and TOGa® (later discussed in this review) [31].

Endoluminal Gastric Restrictive Procedures

An alternative treatment for morbid obesity is the ability to endoluminally suture and/or plicate the stomach. The early endoscopic suturing devices have been developed primarily for the treatment of gastroesophageal reflux disease (GERD). However, the results to date have been quite controversial and largely debated [32].

Similar principles have been recently reintroduced in bariatric surgery in order to produce a gastric plication of the stomach layers (both mucosa and sub-mucosa, or even with full-thickness bites) with subsequent reduction of the gastric volume.

EndoCinch

The first FDA-approved device was the EndoCinch Suturing System® (Davol Inc., Cranston, RI, USA) developed by a group led by Paul Swain. The device is inserted over a standard endoscope and a series of full-thickness sutures can be placed in two rows to replicate the concept of a vertical gastroplasty [33]. In 2008, Fogel et al. reported a series of 64 obese patients treated by means of an endoscopic vertical gastroplasty with a 1-year follow-up. They registered a significant reduction in BMI at 12 months (mean [SD] BMI 39.9 ± 5.1 kg/m2 vs 30.6 ± 4.7 kg/m2; P < .001) and a percentage of excess weight loss (% EWL) (SD) of 21.1 ± 6.2, 39.6 ± 11.3, and 58.1 ± 19.9 at 1, 3, and 12 months respectively. Some of those results are comparable with the control group treated with LRYGB [34]. Fogel’s excellent results could not be reproduced in further studies.

Other suturing devices followed: Stomaphyx®, the NDO plicator®, the EndoStitch®, and the TOGa system®, SafeStitch, RESTORe Suturing System™, TERIS, Anubis, Spider, Endosamurai, Incisionless Operating Platform® (IOP), Overstitch and others.

While the general concept is similar, the exact technology does defer among the devices. EndoCinch® fires a straight threaded needle through a tissue fold obtained by suction [35], while the Eagle Claw®-Overstitch uses a curved needle to allow an intracorporeal knot [36]; the TOGa system uses a set of transoral endoscopically guided staplers [37].

TOGa

Favorable results have been reported for a series of patients treated by mean of TOGa system (Satiety Inc., Palo Alto, CA), used to create a stapled restrictive pouch along the lesser curvature of the stomach [32] as well as other suturing devices.

This system is composed of 2 disposable stapling devices: the TOGA Sleeve Stapler and the TOGA Restrictor. The first is used to create a vertical sleeve along the lesser curvature of the stomach, approximately 8 cm in length and 2 cm in diameter. The second is used to reduce the sleeve outflow size by creating folds at the distal end of the pouch [37].

A 60-F bougie is introduced through the mouth into the esophagus over a guidewire. The TOGA Sleeve Stapler is then introduced over the wire and a small endoscope is routed through a channel in the device. Once the stomach cavity is reached, a septum with attached retraction wire spreads and orient the stomach tissue, while suction is applied from the vacuum pods included in the device. Three rows of titanium staples are usually delivered to create a staple line that connects the anterior and posterior stomach, beginning 1 cm proximal to the Z line and extending distally 4.5 cm, parallel to the lesser curvature [38]. According to the latest method tested, a second staple line is added distally. The result of this procedure is a small, restrictive pouch along the lesser gastric curvature [37].

The first human multicenter study in 2007 enrolled 21 patients and reported good results in terms of safety and a reduction of EWL of 16.2%, 22.6%, and 24.4% respectively at 1, 3, and 6 months. However, this first study demonstrated that there were evident gaps in the staple line in 13 of the 21 patients. At that time, only one staple line was created [32]. Following this first trial, an Italian study analyzed the effects of the TOGA on insulin sensitivity and secretion on a series of 9 patients. Insulinemia was significantly reduced at fast and at 120′ after OGTT, as well as the insulin secretion rate (from 235.05 ± 27.50 to 124.77 ± 14.50 nmol/min/m2, p = 0.021) while insulin sensitivity increased (from 348.45 ± 20.08 to 421.18 ± 20.84 ml/min/m2, p = 0.038). Total insulin secretion rate was demonstrated to correlate with weight, fat mass, and BMI [38]. A second prospective trial with a 1-year follow-up ended in 2011 tested the effects on gap prevention of a second staple line added distally and involved 53 patients. Nevertheless, 7 patients had a gap on the proximal part of the staple line, 16 had gaps between staple lines, and 2 had a combination of the gap types. This replicates the same complication of Mason’s gastroplasty that lead to the McLean modified technique. Gap presence negatively correlates with the efficacy of the procedure and remained an unsolved problem of the TOGA procedure. Patients with no or small gaps (< 15 mm) had a responder rate of 87.5% whereas patients with large gaps (> 15 mm) had a rate of 45.5% (p < 0.0027). There were only mild side effects related to the procedure, including nausea, vomiting, abdominal pain, throat pain and dysphagia which resolved within 1 week. At routine radiographic post-procedure control, one patient was diagnosed with an asymptomatic pneumoperitoneum, which resolved without any complication. The second TOGA trial did confirm the promising results of the first, showing a % EWL of 29.3 ± 11.6% at 3 months, 36.8 ± 15.7% at 6 months, and 38.7 ± 17.1% at 12 months and improvements in the metabolic profile of the participants were reported as well [38]. Unfortunately, even with such promising results, further development of the TOGA System is uncertain due to the parent company (Satiety, Inc.) which declared insolvency and sold its assets due to lack of funding for pursuing clinical studies [39].

RESTORe

A new generation of suturing device (RESTORe Suturing System™-Bard Inc.) is currently being evaluated in the TRIM trial (Transoral Gastric Volume Reduction as an Intervention for Weight Management). It is a multicenter, prospective, non-randomized study involving two centers (Brigham and Women’s Hospital, Boston, Massachusetts and Cleveland Clinic, Cleveland, Ohio), with a 2-year follow-up planned.

The RESTORe Suturing System is a single-intubation, multistitch, endoscopic suturing device designed to place sutures through the muscular wall of the stomach and approximate gastric tissue. When activated, the system deploys a 3–0 polypropylene suture through the tissue in the suction chamber and deposits the suture tag [40]. Eighteen subjects with a BMI 30–45 kg/m2 (mean 38.6 kg/m2) underwent a gastric volume reduction procedure, each patient required four to eight plications (mean 6), and the average procedure time was 125 min. No serious or significant procedure-related complications were recorded. At 12 months of follow-up, EWL was greater than 30% for half of the patients and EWL 30.5 ± 16.8% for subjects with a BMI between 30 and 35. Unfortunately, those results were not durable over time, as the sutures did not remain in place [39].

TERIS

The Transoral Endoscopic Restrictive Implant System (TERIS–Barosense, Inc.) uses an endoscopic guidance to transorally implant a prosthesis placed at the level of the cardia to decrease the size of the food reservoir at the upper part of the stomach to induce early and prolonged satiety. Five gastric plications are created about 3 cm below the gastroesophageal junction using an articulating endoscopic circular stapler. The gastric restrictor is subsequently attached to the gastric wall by means of silicon anchors inserted through the gastric plications. The first plication is created just above the lesser curve of the stomach. The primary clinical results have been observed in a female patient with a BMI of 46 kg/m2. No major complications during and after the procedure were reported. The EWL was 21% and 26% at 3 and 6 months, respectively. The observation of a high rate of implant obstruction led to the development of a second generation of the implant [41]. Subsequent study was published by Fockens et al. that focused on safety and efficacy using the TERIS implant. This study was a short-term trial including 13 patients with a BMI between 40 and 50 kg/m2 or 35 and 40 kg/m2 with comorbidities. The follow-up was for 3 months after the procedure. In summary, one patient sustained intraprocedural gastric perforation related to stapler malfunctioning. Two other patients had a pneumoperitoneum that was treated conservatively in one case and deflated by a percutaneous hollow needle in the other. Twelve of 13 patients had a successful placement of the implant. At 3 months of follow-up, the authors report a median excess weight loss of 28%, and a median BMI decrease of 4.2 kg/m2 (from 42.1 to 37.9 kg/m2) [42]. After the device and the general conduction of the procedure were modified, a new study was performed including 18 patients. Three adverse events occurred (2 pneumoperitoneum, 1 perforation). In 62.5% of patients, the anchors remained intact for 6 months. The mean EWL after 6 months was 30.1% (± 9.8), weight loss was 15.1% (± 5.3), and excess BMI loss was 37.7% (± 12.4). In those who continued the study beyond the first 6 months, weight losses could only partially be maintained due to the detachment of anchors and the unimpeded passage of food. Because of the serious adverse events and the poor durability of the implant, the company decided to discontinue the development of the TERIS system [43].

Safestitch

Safestitch (TransEnterix, Inc.) is an intraluminal gastroplasty device that differs from the ones mentioned above by not being fixed at the endoscope. It is designed to approximate the stomach walls using suction and applying sutures after mucosal excision. Only one pilot study is present in the literature on 5 obese patients with mixed results [44].

Satisphere

Satisphere requires endoscopic implantation and is composed of a nitinol backbone and spheres made of polyethylenterephthalat (PET) with two pigtails at each end. The device is designed to stay in place by mimicking intestine anatomy, following the duodenal C-shape down to the ligament of Treitz. It is implanted via endoscopy into the stomach and duodenum and requires general anesthesia. The results of a study reported an average weight loss of 4.6 kg and BMI reduction of 1.6 in the treatment group (21 patients), 6.7 kg weight loss and a BMI reduction of 2.4 in the completers group (12 subjects), and 2.2 kg weight loss with a BMI reduction of 0.6 in the control group after 3 months. Although patients in the treatment group lost more weight, the results did not reach statistical significance. However, patients who completed the study lost significantly more weight than the controls and EWL was greater than 10%.

Satiety was thought to be the underlying reason of weight loss due to Satisphere implant. GLP-1 secretion was also analyzed in correlation to satiety in the same study. In patients with the device in place, glucose absorption and insulin secretion were delayed. Peak values for glucose and insulin were reached after 60 min, while in the same patients without the device, maximum levels for glucose and insulin were documented after only 30 min. In addition, GLP-1 levels remained almost entirely stable with the endoluminal mechanical device in place. Such data indicate that delaying duodenal transit time prolongs glucose absorption and insulin secretion. This might affect GLP-1 secretion in a way that leads to a continuous GLP-1 production rather than a dynamic secretion following nutrient intake. Therefore, the device resembles exogenous GLP-1 application and this effect might be, at least in part, responsible for the observed weight loss. The study was prematurely terminated due to high migration rates: 10 migrations occurred. Three Satisphere were excreted spontaneously without causing any damage to the intestine, one was removed via upper endoscopy and four by colonoscopy. Two had to be operated laparoscopically. One of the latter device removals required treatment in the intensive care unit with consecutive surgical interventions including hemicolectomy. Therefore, serious adverse events occurred in 10 out of 21 patients in the treatment group compared to 0 of 10 patients in the control group [45]. Even if conceptually valid, Satisphere’s design has significant technical limitations, especially regarding the anchoring mechanism as testified by the results of previously cited studies. New anchoring solutions are needed in the future in order to safely use such concept in a clinical setting. The last 2 devices described in this chapter are those currently used in clinical practice: we do not explored their results in the treatment of complications, where efficacy has been nicely demonstrated (i.e., endosuturing a sleeve gastrectomy dehiscence) or in secondary procedures (like treatment of weight regain), as this paper aims at a comparison with primary surgery for obesity and metabolic disorders.

POSE

A novel and less invasive surgical option for gastric plication is the POSE procedure that stands for Primary Obesity Surgery Endoluminal. It is based on the use of the Incisionless Operating Platform® (IOP®-USGI Medical, San Clemente, CA, USA) that is made of 3 main components: TransPort Multi-lumen Operating Platform®, a flexible endoscope with four working channels functioning like flexible trocars, allowing users to deploy and use up to three tools simultaneously. It also has insufflation capability. The Platform further consists of a flexible g-Prox® tissue grasper, deployed via one of the four working channels; Expandable Tissue Anchors® with a semi-compliant design to improve force distribution over a large tissue contact to accommodate postoperative swelling and maintain their hold on tissue over time (Fig. 1).

To perform POSE, surgeons advance the USGI TransPort® down the esophagus to the stomach fundus, as a traditional endoscope. The tip of the device is then turned towards the operating site and locked for stabilization. The flexible grasper is used to bite a fold of the stomach mucosa on which the anchors are placed. Each anchor pair is preloaded into a catheter (g-Cath®) and inserted into the grasper before firing. Several folds are created in this way to reduce gastric fundus and limit its ability to expand. Once the desired capacity is reached, the device is removed through the esophagus. Initial human trial has been conducted in the USA and Europe confirming the promising results of previous animal trial by De La Mora et.al. [46]. A prospective observational study was undertaken between February 2011 and March 2012 and involved 45 patients: 75.6% female; mean age 43.4 ± 9.2. At baseline: mean absolute weight (AW, kg), 100.8 ± 12.9 (75.5–132.5); body mass index (BMI, kg/m2), 36.7 ± 3.8 (28.1–46.6). All POSE cases were performed with no intraoperative adverse events, no conversions or failed procedures as well as no postoperative re-hospitalizations. There was no mortality in the series and only two minor postoperative adverse events: one case of low-grade fever (resolved with oral antibiotic treatment) and another patient who returned to the hospital on the second postoperative day with chest pain. Minor postoperative side effects included sore throat, stomach pain, nausea, and chest pain. There were three cases of vomiting that resolved within the first 12 h with no requirement of additional hospital stay. All patients were discharged from the hospital within 24 h. Liquid diet was initiated 12 h post-procedure and subsequent solids were introduced by 6 weeks. Follow-up visits were performed in at 1, 2, and 3 weeks, and at 1, 2, 3, 4, 5, and 6 months. The mean 6-month POSE TBWL was 15.5% and more than 80.0% of POSE patients had achieved ≥ 25% EWL. The overall POSE patient mean EWL was MLT 40.0% (calculated by metric) and 49.4% (calculated with BMI 25 as ideal end point). The Authors also report that patients in the current POSE cohort who have reached the 9- and 12-month time points have continued their weight loss trend without complications [47].

Overstitch

The recently redesigned Overstitch, by Apollo Endosurgery (Austin, TX, USA), is able to perform transoral endoscopic gastric volume reduction by a series of endoluminally placed, full-thickness, closely spaced and interrupted sutures through the gastric wall from the prepyloric antrum to part of the fundus.

Although similar in concept, the Overstitch differs from the POSE procedure in several ways: using the IOPlatform, the Gastric restriction is including the whole fundus (as in the laparoscopic gastric plication), while with the OS device restriction is mainly distal, and gastric emptying is delayed; with the latter device, the gastric lumen is reduced in greater volume in order to create a sleeve effect by the large-scale multistitch plications opposing the anterior and posterior gastric walls in a triangular fashion. Although, as said, with a somehow different approach than POSE, the Overstitch also induces delayed gastric emptying with food retention within the residual small fundal compartment [48]. After the preliminary experience by Abu Dayyeh in Rochester (Minnesota, USA) who performed the first transoral endoscopic gastric volume reductions with Overstitch in 4 subjects [49], demonstrating the clinical feasibility of the procedure, clinical studies were undertaken mainly by three high volume centers. The combined data from those centers included 248 patients and demonstrated positive results with a 15.2% TBWL at 6 months and 18.6% at 24 months. Five major adverse events occurred, including 1 case of extra-gastric bleeding, 2 perigastric fluid collections, 1 pneumothorax and pneumoperitoneum requiring chest tube placement, and one pulmonary embolism. Comparable results emerged from the first study undertaken outside the previous facilities, which included a cohort of 112 patients, with approximately the same 15% TBWL and 50% EWL at 6 months post-procedure [50].

Recently, with the aim of lowering the revision rate after endoscopic gastroplasty, a technical variation has been proposed, changing the original triangular stitch plication with 4 rows of sutures proceeding from the gastric incisura to the fundus in a running “Z” pattern. The results on 148 patients from a single center in terms of % EWL at 6 months were comparable to the standard technique [51].

Derivative Procedures

Duodeno-Jejunal Bypass Liner

An endoscopic device applying a concept similar to the biliopancreatic-diversion is the endoscopic duodenal–jejunal bypass sleeve, later renamed duodeno-jejunal bypass liner (DJBL) and commercially branded as Endobarrier (gi-Dynamics, Inc.). The DJBL is a sterilized, single-use endoscopic device, which is employed under radioscopic control. It is composed of a nitinol anchor with tiny lateral barbs for fixation to the duodenal bulb, and an impermeable plastic conduit made of a fluorine polymer 62 cm in length, which prevents contact of bile–pancreatic secretions with chime prior to the proximal segments of the jejunum [52].

This device has a long history: the first human experience was registered in 2007 by Leonardo Rodriguez-Grunert et al. with 12 patients’ prospective, open-label, single-center, 12-week study. They reported problems with the fixation of the device and adverse events related to the device itself, including abdominal pain, nausea, and vomiting, mainly within 2 weeks of implantation. Localized implantation site inflammation was encountered in all patients [53]. Although promising results in terms of EWL and improvement of glycemic profile were achieved in preliminary trials, the same adverse events were reported in each trial [54,55,56].

Subsequently Escalona et al. in 2009 reported a 12-week pilot trial of 10 patients treated with DJBL modified with a 4-mm restrictor orifice distal to the anchor. The baseline BMI was of 40.8 ± 4.0 kg/m2 (range 35.9–47.8 kg/m2). After 12 weeks, the EWL range was 22–64%, corresponding to a total weight loss of 16.7 ± 1.4 kg (range 12.0–26.0) [57]. Despite the initial promising results, the authors still observed some side effects related to the technique as inflammation of the anchoring site, nausea, and vomiting.

According to a recent systematic review and meta-analysis on the effects of the Endobarrier on obesity and type II diabetes, the DJBL patients of the various studies did not achieve similar results to those who underwent RYGB, with the sole exception of the Escalona et al. study [58]. According to a recent meta-analysis initiated by the American Society for Gastrointestinal Endoscopy (ASGE) Bariatric Endoscopy Task Force, the DJBL liner does appear to meet the % EWL Preservation and Incorporation of Valuable endoscopic Innovations (PIVI) threshold at 12 months, resulting in 35% EWL (95% CI, 24–46%) but does not meet the 15% EWL over control required by the PIVI. The study also favors the safety of the procedure, with only 3 severe adverse events reported in 271 implantations [59].

These results on the safety profile of the device were questioned by a more recent systematic review which shows that the use of the DJBL is associated with a wide range of adverse events, with 20.5% graded as moderate and 3.7% graded as severe. Among the latter, 11 hepatic abscesses, 8 gastrointestinal hemorrhage, and 4 esophageal perforations were reported, requiring surgery in 8 cases. Other adverse events reported are esophageal mucosal laceration resulting from the anchor barbs of the DJBL which occurred in 4 patients. With the implant in place, main adverse events were represented by abdominal pain, vomiting and gastrointestinal hemorrhages, migration, ulceration and perforation (probably due to the anchoring mechanism), obstruction and erosion due to the liner. Inflammatory and infectious complications were also reported, accounting for pancreatitis, cholecystitis, and cholangitis. Nearly a quarter of implanted DJBLs were removed early due to adverse events or intolerability of the device. Betzel et al. also analyzed the quality of the adverse events reported, finding an inadequate reporting in most of the studies, resulting in an underestimation of the true incidence of adverse events. The probable cause underlying such adverse events suggested that the anchoring part of the DJBL is likely responsible in 85% of the cases [60]. Recent studies with longer implant times confirm the validity of the DJBL in terms of weight loss and improvement of the glycemic control during the first 12 months. Weight and glycemic control seem to remain stable up to 24 months; however, after explant, worsening of the glycemic control is reported. For this reason, the Authors of the study advice for a maximum implant time of 12 months [61]. Similar conclusions come after a single-center experience of 3 years implant, with sustained weight loss while increasing incidence and severity of serious adverse events over time, thus confirming the 1 year indwelling time limit. The device was never approved by the FDA but was approved in Europe for implantations of 1 year. The CE mark has been recently withdrawn.

The DJBL is a promising device, especially in the super-obese population as a bridge to surgery and in those patients requiring an improvement in glycemic control. New improvements in the design, especially of the anchoring part, are expected to ensure a more favorable safety profile that would lead to a new CE mark certification in the next year.

Gastroduodenojejunal Bypass Sleeve

A device with similar concept was launched by ValenTx (Hopkins, MN, USA) in 2011 named gastroduodenojejunal bypass sleeve (DJBS). Differently than the Endobarrier, it is double the size, being 120 cm in length and secured at the esophagogastric junction with endoscopic and laparoscopic techniques, designed to create an endoluminal gastroduodenojejunal bypass. Laparoscopy is needed for external visualization to ensure transmural anchor placement at the gastroesophageal junction (GE). Twenty-four patients were enrolled in the trial and 22 underwent endoscopic implantation of the bypass sleeve. The implant was maintained for 12 weeks and then removed endoscopically. Two patients (23%) required early explant because of postoperative dysphagia. The observed EWL was 39.7%, and all the patients who presented preoperative diabetes mellitus showed normal blood glucose levels at 12 weeks of follow-up [62]. The Valentx endoluminal bypass therapy is not yet FDA approved nor commercially available and is still a subject of ongoing clinical investigation [63]. The principle of duodenal exclusion may not be the only one effective for weight reduction.

Full Sense Device

It is a temporary device developed by BFKW(Baker, Foote, Kemmeter, Walburn [BFKW] LLC, Grand Rapids, MI, USA) composed of a nitinol wire-mesh funnel coated in silicone inserted through endoscopy above the GE junction with a conical terminal component lodged in the cardia. The pressure force exerted to the cardia and stomach fundus would contribute to the feeling of satiety. To date, the only reported data on the original device comes from a SAGES 2009 presentation in the emerging technology session. Four separate studies were conducted on animals that lost approximately 23% of their body weight whereas controls gained 3% in 28 days. Data regarding 3 female patients were also presented: patient’s mean BMI was 44.0, the device was placed without any complication, no device migration, no ulcers and no compromise of the GE junction. Inflammation, which was present at the time of explant resolved at the 3 weeks postoperative follow-up endoscopy [64, 65]. Recently, a different team developed a new version of the device and tested in the animal setting; however, a high dislodgement rate of the device was reported [66]. The device is currently not FDA/CE approved.

Magnetic Anastomosis Device

The idea of using magnetic force to achieve an alternative way to create intestinal anastomosis date back to 1826 [67] and several different platforms have been invented over time. The underlying concept is that the compressive forces exerted on the bowel wall create a transmural ischemia and subsequent central necrosis while allowing the surrounding tissue to remodel and naturally create a full-thickness anastomosis.

The most promising three are the Incisionless Anastomosis System (IAS), the Incisionless Magnetic Anastomosis System (IMAS) (GI Windows, West Bridgewater, MA, USA), and the Magnamosis (Magnamosis Inc., San Francisco, California, USA).

The IAS, developed by M. Ryou and his team, represents a futuristic approach to endoscopically re-create Roux-en-Y gastrojejunal anastomoses. IAS is the evolution of the Smart Self-Assembling Magnets for Endoscopy (SAMSEN) developed by the same group. Following endoscopic delivery, IAS magnets specifically self-assemble into an octagon capable of creating large-caliber side-to-side anastomoses. When reciprocal macromagnets occupy two different hollow organs (e.g., stomach and jejunum), they align and mate in order to create an anchoring window that can be cut through for an instant anastomosis. Compression anastomosis allows for the creation of a robust, large-caliber fistula after several days with the magnets disengaging with time [68].

Previous studies on the SAMSEN were successfully completed in an animal model [69]. Three-month pressure testing revealed anastomotic tissue to be as robust as native tissue, while necropsy and histology suggested minimal or absent tissue inflammation [70].

A slight modification of the device led to the creation of the IMAS. A nitinol skeleton with configuration memory was introduced to ease the linear positioning of the magnets through an endoscope. Once in place, the device regains the original large size octagonal shape. After encouraging preliminary studies in the animal model, a first pilot human study on the feasibility of a magnetic partial jejunal diversion was conducted by Machytka et al. on 10 patients. With the patient under general anesthesia, pairs of magnets were delivered by a deployment tool advanced through a colonoscope channel into the terminal ileum and proximal jejunum, via simultaneous colonoscopy and enteroscopy, respectively. The mean procedural duration was 115 min. The target one for placement of the 2 IMAS was 50 to 100 cm proximal to the ileocecal valve in the ileum and 50 to 100 cm distal to the ligament of Treitz in the jejunum. Correct positioning was confirmed in all cases through fluoroscopy and laparoscopy; only for the first 6 cases, a grasper was used to facilitate magnet coupling. No leaks or other complications related to the IMAS were reported. The procedure proved to be safe and effective, with a mean TWL of 14.6% and a mean EWL at 12 months of 40.2%. Significant improvements in the glycemic profile were also reported for the 4 diabetic patients of the group [71].

Differently from the previous, the Magnamosis device is composed of a matched pair of self-centering neodymium-iron-boron ring magnets encased in medical-grade polycarbonate. After extensive animal trials, the device demonstrated the ability to consistently create histologically well-formed anastomoses with burst strength comparable with or better than handsewn or stapled anastomoses [72]. Results from the first pilot human study on 5 patients confirmed safety of the procedure, with no leaks or device-related complications.

Magnetic anastomotic procedures are promising, however, especially in case of bariatric surgery, we have doubts about the actual possibility to deliver magnets at a distance of 150 cm from the ileocecal valve solely through endoscopy, thus limiting the malabsorptive effects. Also, we invite to consider the risk that may exist for internal hernias formation. Further studies are definitely needed to clear these and other aspects.

Duodenal Mucosal Resurfacing

Duodenal mucosal resurfacing (DMR) is a novel endoscopic procedure for the treatment of the metabolic alterations of obesity, in particular: type II diabetes, NAFLD, and NASH. The only device tested to date is the Revita system (Fractyl Laboratories, Inc., Lexington, Mass), which consists of a single balloon catheter capable of delivering heat energy. Catheter is placed in the proximal duodenum distal to the papilla, and saline is injected into the sub-mucosal space to lift the mucosa circumferentially. Once activated, the device circulates hot water into the inflated balloon in contact with the duodenal mucosa, causing its ablation. The process is repeated for the next duodenal segments for approximately 10 cm. The procedure has been successfully tested in the animal model and received CE mark. The first clinical experience on 29 patients demonstrated the feasibility and safety profile of the procedure, with no major adverse events reported and only 3 cases of duodenal stenosis. Complete mucosal regrowth was histologically proven at 1 and 3 months after DMR. Modest improvements in HbA1c were reported. Various human trials, including the Revita-1 and Revita-2 trials, are currently ongoing to evaluate long-term safety, efficacy, and durability of DMR [73].

Transluminal Treatment

Endoscopic Aspiration Therapy

Derived from percutaneous endoscopic gastrostomy (PEG) tube technology, endoscopic aspiration therapy (EAT) represents a new way, to induce weight loss by aspirating a portion of ingested meals from the stomach thanks to the AspireAssist Aspiration Therapy System (Aspire Bariatrics Inc., King of Prussia, PA). It is composed of:

  1. (a)

    an all-silicon A-Tube with holes in the intragastric portion to allow aspiration of gastric contents;

  2. (b)

    a Skin-Port valve to prevent gastric leakage, connected to the extra-gastric portion of the A-Tube;

  3. (c)

    a connector to open the Skin-Port valve with an embedded safety device (consisting of a “counter” that tracks the number of times the connector is attached to the Skin-Port until it reaches 115 aspiration cycles when it locks the device and the patient must return to the hospital to continue aspiration therapy);

  4. (d)

    A “companion” device, which is a siphon that allows 2-way flow of fluids thus permitting stomach draining while infusing water in the stomach;

  5. (e)

    a 600-ml soft reservoir that allows subjects to flush tap water into the stomach to facilitate aspiration;

  6. (f)

    a drain tube to dispose the aspirated content into the toilet.

The AspireAssist is FDA approved for the treatment of class II and III obesity.

The procedure is no different from the conventional gastrostomy. Twenty minutes after meals containing more than 200 kcal, patients are required to perform aspiration. They flush food particles out by infusing water into the stomach from the reservoir in 150 to 200 ml increments and then reversing the flow to allow contents to drain out of the stomach. Patients should receive PPI treatment and potassium chloride supplements to reduce acid loss and potential potassium depletion [74]. Results from a 4-year US multicenter randomized controlled study, that continued the PATHWAY study sponsored by the manufacturing company [74], have been recently published [75]. Of the 111 patients randomized into the Aspire therapy group in the original trial, only 15 maintained the device in place for all the 4 years of the new study. Positive results in terms of weight loss have been demonstrated over the years, with reported 14.2%, 15.3%, 16.6%, and 18.7% TWL, respectively at 1, 2, 3, and 4 years, (p < 0.01), which corresponded to 37.1%, 40.8%, 44.7%, and 50.8% EWL [75]. Improvements of comorbidities such as hypertension and diabetes were also present at 1 year and maintained until the 4th year, although there is insufficient evidence to support any effect on cardiometabolic parameters. After 1 year, 18 patients had insufficient weight loss and withdrew from the study. After the 2nd year, 2 serious adverse events occurred: 1 gastric fistula and 1 case of a patient who developed a hole in the A-Tube 20 months after placement. Similar results come from multicenter post-market European registry study [76]. One of the main initial uncertainties of the procedure was the potential risk for the development of unhealthy eating behaviors. No subjects in the treatment arm showed any abnormal eating behaviors, documented with the serial administration of structured psychological assessments over the 4-year period of the study. A possible population that can greatly benefit from Aspire therapy includes patients with a BMI greater than 55 kg/m2 as a bridge therapy towards the traditional bariatric procedures.

Discussion

Morbid obesity has spread worldwide to endemic proportions. To date, surgery represents the most reliable and effective form of treatment for morbid obesity. It delivers the best results in terms of EWL and resolution or improvement of comorbidities.

The laparoscopic approach is the gold standard, and it is now performed in almost all cases (i.e., 99% of cases in the registry of SICOb-Italian Society for bariatric surgery) (https://www.sicob.org/00_materiali/area_medici/indagine/indagine_2017.pdf).

The advent of minimally invasive approach has brought not only a practical revolution, but a cultural one as well: the general concept of less and less invasive therapy has led to rapid development of novel laparoscopic and endoscopic treatment for morbid obesity.

The concept of scarless procedures in which the endoscope is used as the main carrier device, hoping to achieve results at least as good as laparoscopy, has significantly evolved within the last decade. It is driven by a novel procedural paradigm and requires significant technological advancement in order to allow effective as well as safe clinical use. Although being currently almost abandoned in clinical practice, the concept of performing procedures by a NOTES (surgery through natural orifices) or NOSCAR technique (born in the early 2000s) has brought new enthusiasm, both in physicians and engineers involved in the development of mechanical or mechatronics endoscopic instruments.

In contrast with this disruptive vision, after 15 years we observe a very low rate of penetration of these innovative treatments, especially when we compare them to the explosion of the well-established laparoscopic procedures (estimated over 700,000/year by the 2016 IFSO worldwide survey).

Few endoluminal devices are commercially available and routinely used, but every year new instruments are then developed and new applications for existing devices are proposed. Although they have been tested in experimental settings, only a few of them have reached the clinical field after passing safety and efficacy tests, and remain available for clinical use.

Several aspect can explain this apparently frustrating phenomenon:

  • Some producers are no more than start-up companies, and in almost all other cases they are small or medium enterprises: it is then difficult to raise enough funds to support R&D process and further extensive clinical studies;

  • Results are sometimes not repeatable after the first, enthusiastic study led by a single author (a typical example is the experience of Fogel, mentioned in paragraph 3.1)

  • The effort to create devices for endoluminal suturing has been, regularly, frustrated by the lack of mechanical force transmission to the operating tip of the instruments.

  • As a consequence, almost all successful tools are not user friendly, and their diffusion is limited by a complex learning curve and a requirement of high skill levels.

  • All neurostimulators/modulators have a substantial cost, ranging in different countries from10K to 20K euros: this must be taken in consideration in the costs/benefit analysis. This aspect has also limited the experience where the healthcare systems (NHS’s, HMO’s and others) do not reimburse these procedures. Their introduction is then, currently, almost exclusively limited to trials in which the device is provided by the companies.

  • Another pitfall of less and less invasive techniques is the following: they are frequently (commercially…) proposed as so simple that the typical, intensive pre and postoperative work up and follow-up needed for bariatric patients can be simplified or even eliminated. In the medium and long run, this is negatively affecting their results, as a severe bias in the indications is created when a thorough interdisciplinary evaluation of obese patients is missing. Nothing must change in the preoperative evaluation, as well as in the nutritional, psychological p.o. surveillance. As an example, the need for preoperative UGI endoscopy and HP search (recommended by the most recent guidelines) is demonstrated by the high risk of ulcers development in the TransPyloric Shuttle experience.

  • Safety issues have also arisen for some devices in the mid and long-term follow-up, even if results of weight loss and resolution of comorbidities were satisfactory: as mentioned in paragraph 4.1 on duodeno-jejunal bypass liner, a number of severe complications have led the company to repeatedly modify the fixation system.

Taking into consideration this reality, Scientific Societies made some effort to set acceptable targets of weight loss by endoluminal procedures. The most popular is the ASGE/ASMBS-Preservation and Incorporation of Valuable endoscopic Innovations (PIVI) document, published in 2015 [59].

Among other PIVI criteria, it is said that “…endoscopic treatments, intended as a primary obesity intervention in Class II/III obese individuals (body mass index (BMI) >35 kg/m2), should achieve a mean minimum threshold of 25% excess weight loss (% EWL) measured at 12 months….”

This is a questionable point, as the Reinhold scale, the most common criterion used in bariatric surgery, consider satisfactory a 50% excess weight loss (% EWL).

As said, this different “severity” can be justified by the need of supporting the PIVI goal, objectively considering the difficulty to achieve comparable results; on the other end, it makes impossible to compare results based on different success evaluation.

Conclusions

In regard to the different procedures described in this paper, we can say that:

  • lower BMI patients may respond better to the gastric pacing and neuromodulation therapy, and it might be more appealing to patients with moderate or less severe obesity, compared to more invasive surgical procedures. Unfortunately, the lack of significant experience as well as the cost of the devices limits their use in clinical studies and prevents further development of this technology.

  • In the field of endoluminal treatment for morbid obesity, it appears to be technically easy to deliver intragastric implants in order to create an anatomical restriction of the stomach. However, the device “behavior” and risk of migration make those techniques less reliable than current minimally invasive surgical procedures.

  • Alternatively, applying endoluminal sutures on the gastric wall in order to reduce the stomach/pouch volume does produce good short-term results; however, the long-term durability still needs to be significantly optimized in order to achieve results similar to laparoscopic sleeve gastrectomy. The Overstitch is currently the most successful device for endoluminal reduction of the gastric volume. Its mechanisms of action are not exactly comparable to those of a laparoscopic sleeve gastrectomy, or gastric plication, as most of the fundus remains patent, while in the laparoscopic procedures, one of the key steps is considered the vast reduction of the fundus pouch. Although its efficacy has been demonstrated in the hands of expert endoscopic surgeons, it is commonly agreed that this procedure is most effective in patients with low BMI’s (30 to 40). It is then not an alternative for morbidly obese patients within canonical indications.

  • Finally, a variety of alternative therapeutic options have been conceived and proposed: some of them have a limited space in the current bariatric “market,” no one has yet reached a widespread acceptance.

Future Perspectives

As previously pointed out, the lack of mechanical force transmission has limited the suturing easiness of endoscopic devices.

A substantial improvement can only be obtained, in our opinion, by using electronic/robotic force transmission and guidance. In the last 15 years, this development has been blocked by the monopoly created by a single company dealing with robotics. But, microrobotics is evolving and, meanwhile, patents have expired.

Thanks to these new opportunities, new companies and tools will be on the market in the next few years, hopefully creating new, user friendly devices that will enable the innovative procedures to close the currently existing gap.