Endoscopy as an obesity treatment needs the input of other sources. Typical surgical concepts as well as new ones are valuable assets because they make it possible to establish benchmarks and fruitful combinations. One may cite new concepts like digestive neuro-stimulation (theoretically adaptable endoscopically), new operations (e.g., laparoscopic greater curve plication, a debatable procedure, but with highly relevant endoscopic applications; sleeve gastrectomy associated with ileal transposition). New technical approaches are on the spot as well (e.g., single incision laparoscopic surgery, robotic adjunction). Three-dimensional and/or enhanced imagery augment the vision, hence reducing the skills that are required for delicate operations. Last but not least, research is being carried out regarding operations in-between surgery and endoscopy, typically the natural orifice transluminal surgery procedures, e.g., gastro-jejunal anastomosis through stents or magnets.

On the other hand, other fields will contribute to any bariatric procedure, such as patient monitoring (smartsensing) results from the rapidly progressing field of internet on things business. Although in its infancy, the possibility to continuously monitor several health parameters could find potential applications in obese patients, before or after any kind of weight-loss procedure. Coaching tools are not to be ignored in a time when the importance of physical activity is stressed more often (e.g., vibrating platforms).

Biology and pharmacotherapy are the subject of ever ongoing efforts. So far, no drug has challenged the results of surgery, but some are currently being tested and even drugs that have been discarded have been proven useful in combination with bariatric techniques. Moreover, fundamental research has benefited from surgery and could contribute to weight-loss by itself; for instance, microbiota transplantation or brown tissue manipulation.

Several options have been tested since the balloon in the eighties. None of them has yet fulfilled the requirements of a typical bariatric treatment, with sustained weight-loss and regression of comorbidities in the long run. Understandably, they may act as a bridge to more complex surgical procedures and/or attract patients who are not eligible for surgery. Countless procedures have been initiated, but so far very few have met efficacy criteria with published results. They are summarized in Table 1.

(1) Intra-gastric balloons: the initial prototypes were not satisfactory, but since the early nineties one may consider that these devices are reliable. They are usually implanted for 6 months. Only the ORBERA balloon (Apollo Endosurgery Inc., Austin, TX, USA) has been thoroughly reviewed, and was recently analyzed by the ASGE, with a systematic review and meta-analysis using diagnostic and therapeutic thresholds established in 2012 as a part of its preservation and incorporation of valuable endoscopic innovations initiative. Based on a meta-analysis of 17 studies including 1,638 patients, the % excess weight loss (EWL) at 12 months was 25.44% (95% confident interval [CI], 21.47 to 29.4), with three randomized control trials (RCTs; difference in % EWL of 26.9% in favor of balloon over control) [1]. While mostly deemed a safe procedure, one must not forget the adverse events that may occur with a balloon (Fig. 1).

Outside of the familiar and still popular ORBERA, new balloons have been released that aim at longer duration. This can be achieved through refilling the balloon, for instance with the SPATZ balloon (Spatz FGIA Inc., Jericho, NY, USA) [3], or designing a double-balloon volume (DUO-SHAPE Balloon; Reshape, San Clemente, CA, USA) [4]. Perhaps the most interesting devices will be the ones that can be swallowed without endoscopy and anesthesia (OBALON; Obalon Therapeutics, Carlsbad, CA, USA) [5], and even possibly self-excreted (ALLURION-ELIPSE, unpublished data; Allurion Technologies, El Segunto, CA, USA).

(2) Gastric partitioning achieved by endoscopic means is a new concept that might be the most promising. Theoretically a fully stapled pouch such as achieved by surgical means can be transposed through endoscopy. This has even been performed with a device that no longer exists (TOGA; Satiety Inc, Palo Alto, CA, USA) [6]. For the time being, the most promising technique seems to be gastric plication, with two competing devices: USGI-POSE (USGI Inc., San Clemente, CA, USA) and APOLLO-OVERSTITCH (Apollo Endosurgery Inc.). The first one ensures a partial plication with separated transmural stitches and anchors placed along the upper part and the antrum (Fig. 2). The second uses several full-thickness stitches in a triangular pattern, cinched together and repeated along the fundus six to eight times (Fig. 3). Both have been initially tested as re-do procedures for weight-regain after gastro-jejunal bypass, reducing the size of a gastric pouch, and/or gastro-jejunal anastomosis [7]. While the first entails deep and reliable plications, the second ensures a more global shrinking of the lumen with few gaps, and thus may be compared to a bariatric surgical plication (Fig. 4). The most recent and significant experiences with primary cases have been reported by Espinos et al. [8] (USGI) in 2013, and Lopez-Nava et al. [9] (Apollo) in 2015. Espinos et al. [8] reported 45 patients with a follow-up of 6 months. Mean % total body weight loss (TBWL) was 15%. Lopez-Nava et al. [9] reported 50 patients, 13 with a follow-up of more than 1 year. The procedure duration averaged 66 minutes. All patients were discharged within 24 hours, and there were no adverse events. Mean % TBWL was 19.0%±10.8%.

(3) The metabolic field: these techniques aim at mimicking the metabolic effect of the surgical gastric bypass on type 2 diabetes, which relies mostly on duodenal exclusion from food passage. Duodeno-jejunal bypass-sleeve (DJBS), also called Endo-barrier (Fig. 5), has been the most studied of the new devices for the past few years, and has also elicited a comprehensive report from the ASGE. It consists of a 60 cm jejunal tube that is anchored to the proximal duodenum and retrieved 12 months later. Three studies including 105 patients have shown a % EWL of 35.3% at 12 months, and four RCTs showed a difference in % EWL of 9.4% in favor of DJBS [1]. The experimental technique of duodenal resurfacing aims to achieve the same goal.

(4) Other devices can be mentioned but have not yet generated enough data: the Endo-ASPIRE consists of an endoscopically-placed gastrostomy tube and siphon assembly [10]. The food is conveniently stored and then flushed. Patients aspirate gastric contents 20 minutes after meal consumption, removing about 30% of ingested calories. Trans-pyloric materials are also being experimented with, as well as various intra-luminal restrictive devices.

(1) Conditions can be listed, that mostly pertain to occasional circumstances. Companies and physicians alike have to overcome numerous barriers, which are present throughout the development process. Regarding endoscopic devices, these barriers are particularly important. Many events are in a position to kill an innovative device: If the market has not been clearly identified, or is too small, sales will not meet the expectations; likewise if the device is too complex, or too expensive for its application. Many interesting devices can be stalled if investors do not want to finance inevitable delays or if regulatory bodies request additional trials. Clinical results may not pass reimbursement thresholds. The adoption of a new device can take longer than anticipated, and training for experienced physicians might be complicated. Last but not least, any startup can be purchased by a major company in order to eliminate competition.

(2) A strong scientific background regarding bariatric endoscopy is being built. For instance, hormonal studies are already available [11,12], which suggest more or less strong metabolic effects that could match those of surgery. This will allow for valid comparisons between endoscopic and surgical techniques. De Jonge et al. [11] have shown that after 24 weeks of implantation of the Endo-Barrier, patients had lost 12.7±1.3 kg (p<0.01), while hemoglobin A1c had improved from 8.4%±0.2% to 7.0%±0.2% (p<0.01). Both fasting glucose levels and the postprandial glucose response were decreased at 1 week after implantation and remained decreased at 24 weeks. In parallel, the glucagon, glucagon-like peptide 1, and glucose-dependent insulinotropic hormone responses decreased and insulin levels did not change significantly [11]. Mathus-Vliegen and de Groot [12] have studied the effects of a balloon in 42 patients. In group 1, basal cholecystokinin (CCK) levels decreased but meal-stimulated responses remained unchanged after 13 weeks of sham treatment. In group 2, basal and meal-stimulated CCK levels decreased after 13 weeks of balloon treatment. At the end of the second 13-week period, when group 1 had their first balloon treatment, they duplicated the initial 13-week results of group 2, whereas group 2 continued their balloon treatment and reduced meal-stimulated CCK release. Both groups showed reduced meal-stimulated pancreatic polypeptide (PP) secretions at T1 and T2 compared to T0. Changes in diet composition and VAS scores were similar. Improvements in glucose homeostasis partly explained the PP results [12].

(3) One may consider techniques that are ready but require additional studies, e.g., Endo-barrier, Endoplication, and Endo-ASPIRE. On the other hand, some are not yet available (or not anymore) but they could become a priority provided research is carried out, e.g., Endo-rings (TERIS device; Barosense, Menlo Park, CA, USA) [13], Endo-stapling (ACE method; Boston Scientific Corporation, Natick, MA, US) [14], Transpyloric Shuttle (BAROnova, Goleta, CA, USA) [15], the Satisphere method [16], and duodenal resurfacing (FRACTYL, unpublished data; Fractyl, Waltham, MA, USA).

(4) Facing the criticism of those in favor of surgery for everyone is not the least important issue! The current and most common position from the bariatric surgical community states that the efficacy, durability, and long-term clinical utility of endoscopic procedures remain to be established [2]. Although essentially true, this statement overlooks the fact that a majority of obese patients eligible for surgery reject these procedures and/or do not have access to them.