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Review True natural orifice transluminal endoscopic surgery-transgastric cholecystectomy and beyond
Pingting Gao,*orcid, Jia Yu,*orcid, Mingyan Caiorcid, Lili Maorcid, Quanlin Liorcid, Pinghong Zhouorcid

DOI: https://doi.org/10.5946/ce.2024.352
Published online: July 4, 2025

Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China

Correspondence: Christopher Robert Smith Department of Colorectal Surgery, Princess Royal University Hospital, King’s College Hospital NHS Foundation Trust, Farnborough Common, Orpington, BR6 8ND, London, UK E-mail: ChristopherR.Smith@nhs.net
*Pingting Gao and Jia Yu contributed equally as co-first authors.
• Received: December 26, 2024   • Revised: January 27, 2025   • Accepted: January 30, 2025

© 2025 Korean Society of Gastrointestinal Endoscopy

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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  • Natural orifice transluminal endoscopic surgery (NOTES) represents a revolutionary advancement in minimally invasive surgery, eliminating the need for external incisions and offering faster recovery and improved aesthetics. Endoscopic transgastric cholecystectomy (ETGC), a NOTES-based procedure, stands out for its potential to revolutionize gallbladder removal by offering a truly scarless alternative to traditional laparoscopic cholecystectomy. This review explores the historical development of cholecystectomy, evolution of NOTES, and emergence of ETGC as a feasible alternative to laparoscopic cholecystectomy. We highlight the technical refinements that have enabled ETGC, including innovations in full-thickness resection and suturing techniques, and discuss challenges such as visibility, orientation, and wound closure. Finally, we examine the role of robotic platforms in enhancing precision and expanding clinical applications by positioning ETGC as a transformative technique in the era of minimally invasive surgery.
  • Keywords: Cholecystectomy; Minimally invasive surgical procedures; Natural orifice endoscopic surgery
Natural orifice transluminal endoscopic surgery (NOTES) has emerged as a revolutionary technique in the field of minimally invasive surgery. Since its introduction in 2000 by Professor Kalloo, this innovative approach has eliminated the need for external incisions, thereby offering patients a scarless alternative to traditional procedures that is associated with a faster recovery.1-3 Among the various applications of NOTES, endoscopic transgastric cholecystectomy (ETGC), which was introduced in 2021, is one of the most promising advancements.4 By utilizing the stomach as an entry point, ETGC allows the removal of the gallbladder without the need for abdominal incisions, reducing complications such as infection, pain, and scarring. This review traces the evolution of cholecystectomy from open surgery to laparoscopic methods and highlights ETGC as a promising extension of NOTES while addressing its technical challenges and future directions.
Gallstones are a frequently occurring benign condition of the digestive system, affecting 10% to 20% of adults worldwide, with incidence rates on the rise.5,6 In 1867, Dr. John Stough Bobbs, known as the “father of gallbladder surgery,” first removed gallstones incidentally while excising an abdominal tumor.7 In 1882, Dr. Carl Langenbuch of Germany performed the world’s first cholecystectomy, proposing the “gallbladder stone bed theory” that linked the gallbladder to both gallstone formation and an increased risk of gallbladder cancer.8 This theory supports the use of cholecystectomy as a preventive measure, characterizing the procedure as a standard practice in surgical treatment. In 1985, Dr. Erich Mühe performed the first laparoscopic cholecystectomy (LC), which has since become the “gold standard” for treating gallstones by reducing the invasiveness of the procedure while offering outcomes comparable to those of mini-cholecystectomy.9-12 NOTES emerged in 2004, when Kalloo’s team demonstrated gastric access in a porcine model, inspiring further research into incision-free surgery.13,14 This breakthrough significantly broadened the scope of minimally invasive endoscopic surgery and inspired endoscopists worldwide to explore the potential of endoscopic cholecystectomy. In 2007, Marescaux et al.15 performed the first human transvaginal NOTES cholecystectomy utilizing an umbilical puncture needle to create a pneumoperitoneum without abdominal incisions, showcasing its feasibility and spurring clinical trials.
NOTES uses natural orifices, such as the stomach, colon, and vagina, to access the peritoneal cavity. Clinical trials, including the Natural Orifice Surgery Consortium for Assessment and Research (NOSCAR) study,16 have confirmed its safety and efficacy, reporting outcomes similar to those of LC in terms of complications and recovery, while offering aesthetic and pain-related benefits. In the NOSCAR study, 90 participants were divided into three groups: (1) conventional multiport LC (control), (2) transgastric cholecystectomy, and (3) transvaginal cholecystectomy. However, limitations in suturing devices initially restricted the use of transgastric approaches, and only four patients underwent transgastric cholecystectomy. The results showed no significant differences among the groups in terms of intraoperative complications, hospital stay, postoperative medication use, or pain scores, with the NOTES group showing slightly better aesthetics and pain relief. Although the operating time was longer in the NOTES group, no conversions to laparoscopic or open surgery were required. Advances in endoscopic full-thickness resection (EFTR) and suturing techniques have since addressed these barriers, thereby enabling more complex procedures and expanding the application of NOTES. A meta-analysis comparing hybrid NOTES with LC revealed that while the NOTES group had a higher intraoperative conversion rate, the postoperative wound and perioperative complications were similar, and the lower postoperative pain scores in the NOTES group17 further validated NOTES as a viable alternative to LC, particularly for selected patients requiring scarless interventions.
Multiple NOTES approaches, including the transvaginal, transgastric, and transcolonic routes, have been investigated for cholecystectomy. Nevertheless, conventional NOTES techniques predominantly rely on laparoscopic assistance or supplementary devices (e.g., secondary endoscopes or transabdominal instruments) to ensure procedural safety and efficacy.18,19 Among the natural orifices explored for NOTES cholecystectomy—the stomach, colon, and vagina—the transgastric approach was the first route to be investigated.18,20 In 2020, our institution pioneered a novel pure ETGC technique,4 which uniquely accomplished complete gallbladder resection using a single-channel endoscope without ancillary incisions or laparoscopic guidance.
Current eligibility criteria for ETGC at our center are as follows: (1) symptomatic gallbladder pathology; (i) gallstone-related diseases (e.g., recurrent biliary colic and cholecystitis); (ii) gallbladder polyps with high-risk features (e.g., ≥10 mm, rapid growth); (2) favorable anatomical conditions: minimal anticipated intra-abdominal adhesions (preferably no prior abdominal surgery); and (3) low surgical risk profile: American Society of Anesthesiologists class I–II.
Absolute contraindications are as follows: (1) severe cardiopulmonary comorbidities or decompensated systemic disease; (2) suspected or confirmed gallbladder malignancy; (3) esophageal stricture or surgically altered gastric anatomy (e.g., post-gastrectomy, paraesophageal hernia); and (4) coagulopathy (platelet count < 90 ×109/L4,16 or uncorrected bleeding diathesis).
While these criteria provide a preliminary framework for ETGC patient selection, multicenter validation and long-term outcome studies are imperative to standardize the indications, refine technical workflows, and establish comparative effectiveness with LC.
The steps involved in the procedure are as follows (Fig. 1): (1) creating a controlled perforation in the gastric wall; (2) dissecting the gallbladder triangle to achieve the “critical view of safety”; (3) removing the gallbladder via a snare and securing hemostasis; and (4) closing the gastric incision using advanced suturing techniques, such as purse-string suturing and metallic clips.
ETGC offers significant advantages over LC because it eliminates the need for abdominal incisions. This avoids complications such as postoperative incision pain, wound infections, abdominal wall hernias, and skin scarring, leading to faster recovery and a truly scarless and painless surgical experience (Table 1).4,16,17,21-23
Among the various access routes for endoscopic cholecystectomy, ETGC stands out because of its shorter and more direct pathways. The anterior wall of the gastric antrum is typically chosen as the access point to minimize the risk of vascular injury and leakage of gastric acid or its contents. Additionally, the acidic environment of the stomach helps reduce the risk of infection. With advancements in the earliest approaches, ETGC benefited from a relatively well-established set of instruments and devices. Moreover, unlike the transvaginal approach, ETGC is not constrained by sex, further enhancing its versatility and clinical utility.24
However, ETGC presents certain challenges. The primary challenge in ETGC is the visualization and dissection of Calot’s triangle, which is a critical step for achieving complete endoscopic removal of the gallbladder (Fig. 2). This highlights the need for endoscopists to thoroughly understand the intricate anatomy of the gallbladder triangle. The use of a flexible endoscope and an oblique approach reduces visibility within the peritoneal cavity owing to limited lighting.25 Moreover, maintaining proper orientation within the abdominal cavity can be difficult because of the instability in an inverted view.26 Inadequate dissection of this area poses significant risks, including injury to the common bile duct and subsequent severe bleeding. Preoperative endoscopic retrograde biliary drainage may reduce the risk of bile duct injury.
Closing a gastric incision is more technically demanding than closing a colonic incision because of the thicker gastric wall, necessitating advanced skills in endoscopic full-thickness gastric wall defect closure. At our center, we primarily use three methods for gastric wall closure: purse-string suturing with metal clips and nylon threads, resolution clips (Boston Scientific Corporation) combined with harmonic clips, and the OverStitch suturing device (Apollo Endosurgery Inc.). Extensive studies have demonstrated that purse-string suturing is an effective and safe method for closing full-thickness defects of the gastrointestinal wall.21,27 Metallic clips are commonly used for endoscopic wound closure in clinical practice. Boston Scientific Resolution clips, with a span of up to 15 mm, can approximate larger defects when combined with standard metal clips.28 The OverStitch device is an innovative endoscopic suturing tool that enables continuous suturing without exiting the gastrointestinal tract, thereby significantly enhancing operational flexibility. Its strong tissue-apposition capabilities make it particularly effective in managing large gastrointestinal defects.29,30
The postoperative complications may include abdominal adhesions, delayed abdominal bleeding, postoperative cholecystitis, jaundice caused by impacted stones in the bile duct, and bile leakage. Close monitoring of the clinical signs and comprehensive postoperative care are essential for managing these risks. To date, our center has performed 40 ETGC procedures and reduced the average surgery time from 1 to 4 hours, with an average hospital stay of 3 days. No complications were reported during follow-up, underscoring the safety and efficacy of ETGC.
The execution of ETGC is currently limited to skilled endoscopists because of the technical demands of flexible endoscopes, which lack triangulation, traction, and tactile feedback.31,32 Robotic platforms have emerged as a promising solution to these limitations by enhancing endoscope control with haptic feedback and multi-arm flexibility for precise tissue manipulation.33,34 Studies using porcine models have demonstrated that robotic platforms improve efficiency and reduce variability in EFTR.35,36 By standardizing techniques and reducing learning curves, robotic technology is expected to expand the applications of ETGC, heralding a transformative era for NOTES procedures through continuous innovation in endoscopic instruments.
Since the first time it was performed by Professor Kalloo in 2000, NOTES has advanced significantly, overcoming technical challenges such as the limitations of flexible endoscopes and achieving reliable gastrointestinal closure.37 Advancements in EFTR have opened new possibilities, allowing endoscopists to excise lesions throughout the digestive tract and seamlessly transition between the intraluminal and extraluminal approaches.38,39 Innovations in suturing devices have rendered perforation a manageable complication, thereby substantially expanding the capabilities and applications of NOTES.40-42
ETGC represents a significant advancement in the pursuit of scarless, minimally invasive surgery. By eliminating abdominal incisions, ETGC minimizes postoperative pain, accelerates recovery, and prevents complications such as wound infection and scarring. As part of the NOTES paradigm, ETGC offers distinct advantages, including a shorter surgical pathway and a reduced risk of infection, making it a compelling alternative to traditional LC. Despite these benefits, ETGC presents challenges such as limited intraoperative visibility, difficulties in maintaining orientation, demanding techniques for gastric wall closure, and the possibility of complications. Additionally, the potential for complications necessitates skilled endoscopists, advanced suturing expertise, and standardized perioperative management. New intraoperative navigation systems, advanced imaging technologies, and robotic platforms promise to enhance ETGC’s precision and feasibility, expanding its clinical applications.
Ongoing research and development in NOTES, EFTR, and suturing devices will continue to advance ETGC, paving the way for its broader adoption and reinforcing its role as a transformative approach in minimally invasive surgery.
Fig. 1.
Endoscopic transgastric cholecystectomy. (A) Incision of the anterior wall of the gastric antrum to establish an abdominal entry channel. (B) Exposure of the gallbladder. (C) Dissection of the gallbladder from the gallbladder bed starting from the fundus. (D) Dissection of the cystic duct and the gallbladder triangle. (E) Removal of the gallbladder and ligation of the cystic duct remnant with nylon thread. (F) Pursed-string suturing of the gastric incision using a combination of metal clips and nylon threads. (G) Complete removal of the gallbladder under endoscopy. (H) In this case, the gallbladder was completely filled with stones, necessitating cholecystectomy.
ce-2024-352f1.jpg
Fig. 2.
Anatomy of Calot’s triangle.
ce-2024-352f2.jpg
Table 1.
Comparisons between ETGC and LC
ETGC LC
Advantages
 1. No abdominal incisions, achieving scarless surgery: performed via natural orifices (transgastric), avoiding visible scars4 1. Standardized procedure with broad applicability: indicated for >90% of gallbladder diseases22
 2. Reduced incision-related complications: theoretical lower risks of incisional hernias and infections (based on evidence from small-scale studies)16,17 2. Superior intraoperative visualization and precision: multiport access reduces bile duct injury rates (<0.5%)23
 3. Potentially shorter recovery times: limited reports indicate shorter hospital stays than LC, which requires further validation16,17 3. Long-term safety validated by decades of practice: proven efficacy and safety across diverse populations22
Disadvantages
 1. Technically challenging with limited visualization: single-channel endoscopy restricts the surgical field, complicating dissection of Calot’s triangle4 1. Abdominal incision-related complications: risks include incisional hernias (2%–5%) and wound infections (1%–3%)22
 2. Risk of gastric closure failure: gastric leak rates of 1%–2%, dependent on advanced endoscopic suturing skills21 2. Postoperative pain management required: multimodal analgesia protocols are standardized but necessary23
 3. Strict patient selection criteria: limited to American Society of Anesthesiologists I–II patients without intra-abdominal adhesions or anatomical variations16 3. Aesthetic concerns in comparison with ETGC: visible scars, particularly in multiport approaches4

ETGC, endoscopic transgastric cholecystectomy; LC, laparoscopic cholecystectomy.

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      True natural orifice transluminal endoscopic surgery-transgastric cholecystectomy and beyond
      Image Image
      Fig. 1. Endoscopic transgastric cholecystectomy. (A) Incision of the anterior wall of the gastric antrum to establish an abdominal entry channel. (B) Exposure of the gallbladder. (C) Dissection of the gallbladder from the gallbladder bed starting from the fundus. (D) Dissection of the cystic duct and the gallbladder triangle. (E) Removal of the gallbladder and ligation of the cystic duct remnant with nylon thread. (F) Pursed-string suturing of the gastric incision using a combination of metal clips and nylon threads. (G) Complete removal of the gallbladder under endoscopy. (H) In this case, the gallbladder was completely filled with stones, necessitating cholecystectomy.
      Fig. 2. Anatomy of Calot’s triangle.

      Fig. 1.

      Fig. 2.

      True natural orifice transluminal endoscopic surgery-transgastric cholecystectomy and beyond
      ETGC LC
      Advantages
       1. No abdominal incisions, achieving scarless surgery: performed via natural orifices (transgastric), avoiding visible scars4 1. Standardized procedure with broad applicability: indicated for >90% of gallbladder diseases22
       2. Reduced incision-related complications: theoretical lower risks of incisional hernias and infections (based on evidence from small-scale studies)16,17 2. Superior intraoperative visualization and precision: multiport access reduces bile duct injury rates (<0.5%)23
       3. Potentially shorter recovery times: limited reports indicate shorter hospital stays than LC, which requires further validation16,17 3. Long-term safety validated by decades of practice: proven efficacy and safety across diverse populations22
      Disadvantages
       1. Technically challenging with limited visualization: single-channel endoscopy restricts the surgical field, complicating dissection of Calot’s triangle4 1. Abdominal incision-related complications: risks include incisional hernias (2%–5%) and wound infections (1%–3%)22
       2. Risk of gastric closure failure: gastric leak rates of 1%–2%, dependent on advanced endoscopic suturing skills21 2. Postoperative pain management required: multimodal analgesia protocols are standardized but necessary23
       3. Strict patient selection criteria: limited to American Society of Anesthesiologists I–II patients without intra-abdominal adhesions or anatomical variations16 3. Aesthetic concerns in comparison with ETGC: visible scars, particularly in multiport approaches4
      Table 1. Comparisons between ETGC and LC

      ETGC, endoscopic transgastric cholecystectomy; LC, laparoscopic cholecystectomy.

      Table 1.

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