Safety is a concern in natural orifice transluminal endoscopic surgery (NOTES) mediastinoscopy. The objective of this study was to compare the safety of NOTES mediastinoscopy with video-assisted mediastinoscopy (VAM).

Twenty-four pigs were randomly assigned to NOTES or VAM. Thirty-minute mediastinoscopies were performed with the identification of seven predetermined structures. The animals were euthanized after 7 days and necropsy was performed.

Mediastinoscopy was not possible in one animal in each group. There were more intraoperative adverse events with NOTES than VAM (7 vs. 2, P = 0.04); hemorrhage was the most frequent adverse event (4 and 1, respectively). At necropsy, pathological findings were observed in 13 animals (9 NOTES and 4 VAM; P = 0.03). Inflammatory parameters were not different between groups and were not related to adverse events.

Systematic NOTES mediastinoscopy is possible and comparable to VAM in terms of number of organs identified and inflammatory impact. However, the safety profile of NOTES mediastinoscopy has to be improved before it can be adopted in a clinical setting.

Natural orifice transluminal endoscopic surgery (NOTES) has emerged as one of the most exciting areas in the field of minimally invasive surgery during the last decade. NOTES comprises a wide spectrum of procedures from various natural accesses such as transgastric or transvaginal routes, and different direct-target or distant-target organs. Since polypectomy was first performed in 1955, major advances in technology and refinement of endoscopic technique have allowed endoscopic surgeons to perform complex endoscopic interventions such as endoscopic submucosal dissection. Recognizing the safety and feasibility of submucosal tunnelling and mucosal closure, endoscopic resection beyond the level of mucosa has been increasingly reported. One of these procedures, peroral endoscopic myotomy for achalasia, has gained much popularity and excellent results have been published comparable with that of traditional Heller's cardiomyotomy. Submucosal tunnelling endoscopic resection has also been reported for tumours situated in the muscular layer of the gastrointestinal tract. To overcome the difficulty of intestinal closure after NOTES, researchers have collaborated with the industry in developing different endoscopic suturing devices such as the Eagle Claw (Olympus Medical Systems, Tokyo, Japan) and Overstitch™ (Apollo Endosurgery, Austin TX, USA). These devices allow precise and secure suture application with the ordinary flexible endoscope, achieving tissue approximation similar to open surgical suturing. To further expand the potential of NOTES, investigators had also developed multitasking platforms enabling the performance of surgical procedures of even higher complexity. Recently, a novel endoscopic robotic system 'Master and Slave Transluminal Endoscopic Robot' (MASTER) has been developed. Early results of endoscopic resection utilizing this system have been encouraging, allowing both experts and novices in endoscopy to perform difficult endoscopic resection with a high degree of flexibility.

Single-port transumbilical surgery is a well-established platform for minimally invasive abdominal surgery. The aim of this study was to compare the hemodynamics and inflammatory response of a novel transumbilical technique with that of a conventional transthoracic technique in thoracic exploration and lung resection in a canine model.

Sixteen dogs were randomly assigned to undergo transumbilical thoracoscopy (n = 8) or standard thoracoscopy (n = 8). Animals in the umbilical group received lung resection via a 3-cm transumbilical incision in combination with a 2.5-cm transdiaphragmatic incision. Animals in the standard thoracoscopy group underwent lung resection via a 3-cm thoracic incision. Hemodynamic parameters (e.g., mean arterial pressure, heart rate, cardiac index, systemic vascular resistance, and global end-diastolic volume index) and inflammatory parameters (e.g., neutrophil count, neutrophil 2',7' -dichlorohydrofluorescein [DCFH] expression, monocyte count, monocyte inducible nitric oxide synthase expression, total lymphocyte count, CD4+ and CD8+ lymphocyte counts, the CD4+/CD8+ratio, plasma Creactive protein level, interleukin-6 level) were evaluated before surgery, during the operation, and on postoperative days 1, 3, 7, and 14.

Lung resections were successfully performed in all 16 animals. There were 2 surgery-related mortality complications (1 animal in each group). In the transumbilical group, 1 death was caused by early extubation before the animal fully recovered from the anesthesia. In the thoracoscopic group, 1 death was caused by respiratory distress and the complication of sepsis at 5 days after surgery. There was no significant difference between the two techniques with regard to the hemodynamic and immunologic impact of the surgeries.

This study suggests that the hemodynamic and inflammatory changes with endoscopic lung resection performed by the transumbilical approach are comparable to those after using the conventional transthoracic approach. This information is novel and relevant for surgeons interested in developing new surgical techniques in minimally invasive surgery.

Natural orifice transluminal endoscopic surgery (NOTES) has been established in animal models and human studies.

The aim of this study was to assess the feasibility and efficacy of applying transgastric NOTES to diagnose patients with ascites of unknown origin.

Prospective study.

Two university and teaching hospitals.

Patients with ascites of unknown origin.

Diagnostic transgastric NOTES.

Characteristic of ascites cases, conditions of the abdominal cavity, diagnostic accuracy, adverse events, and follow-up time.

Transgastric NOTES was performed successfully in 78 patients with ascites of unknown origin, and 72 cases (92.3%) were clearly diagnosed. They included malignant tumors (39 cases), tuberculous peritonitis (28 cases), chronic hepatic inflammation (3 cases), necrotizing lymphadenitis (1 case), and eosinophilic serositis of the small intestine (1 case). In addition, there were 6 nondiagnostic cases, and no severe adverse events were found.

Nonrandomized control analysis.

Transgastric NOTES in combination with biopsy can elucidate the causes of ascites of unknown origin in the majority of cases. Therefore, it is a feasible and effective approach to access the peritoneal cavity and also a valuable modality to detect the cause of diseases with ascites of unknown origin.

Transesophageal natural-orifice transluminal endoscopic surgery (NOTES) mediastinoscopy has been described as a feasible, less-invasive alternative to video-assisted mediastinoscopy (VAM). We aimed to investigate hemodynamic and respiratory effects during transesophageal NOTES mediastinoscopy compared with VAM.

This was a short-survival experiment in 20 female pigs randomized to NOTES (n = 10) or VAM (n = 10) mediastinoscopy. In the NOTES group, an endoscopist accessed the mediastinum through a 5-cm submucosal tunnel in the esophageal wall, and CO2 was used to create the pneumomediastinum. Conventional VAM was carried out by thoracic surgeons. A 30-minute systematic exploration of the mediastinum was then performed, including invasive monitoring for hemodynamic and respiratory data. Blood samples were drawn for gas analyses.

All experiments except 2 in the NOTES group (one because of technical difficulties, the other because of thoracic lymphatic duct lesion) were completed as planned, and animals survived 24 hours. Also, 3 animals in the NOTES group presented a tension pneumothorax that was immediately recognized and percutaneously drained. VAM and NOTES animals showed similar pulmonary and systemic hemodynamic behavior during mediastinoscopy. Pulmonary gas exchange pattern was mildly impaired during the NOTES procedure, showing lower partial arterial oxygen pressure associated with higher airway pressures (more important in animals that presented with pneumothorax).

NOTES mediastinoscopy induces minimal deleterious respiratory effects and hemodynamic changes similar to conventional cervical VAM and could be feasible when performed under strict hemodynamic and respiratory surveillance. Notably, serious complications caused by the injury of pleura are more frequent in NOTES, which mandates an improvement in technique and suitable equipment.

Transoral endoscopic surgery has been shown to be feasible and safe in both humans and animal models. The purpose of this study was to evaluate the safety and efficacy of transoral and conventional thoracoscopy for thoracic exploration, surgical lung biopsy, and pericardial window creation.

The animals (n = 20) were randomly assigned to the transoral endoscopic approach group (n = 10) or conventional thoracoscopic approach group (n = 10). Transoral thoracoscopy was performed with a flexible bronchoscope via an incision over the vestibulum oris. In conventional thoracoscopy, access to the thoracic cavity was obtained through a thoracic incision. Surgical outcomes (body weight, operating time, operative complications, and time to resumption of normal diet), physiologic parameters (respiratory rate, body temperature), inflammatory parameters [white blood cell (WBC) counts and C-reactive protein (CRP)], and pulmonary parameters (arterial blood gases) were compared for both procedures.

The surgical lung biopsy and pericardial window creation were successfully performed in all animals except one animal in the transoral group. There was no significant difference in operating times between the groups. The increase in WBC in the transoral thoracoscopy group was significantly smaller on postoperative day 1 than in the conventional thoracoscopy group (p = 0.0029). The transoral group had an earlier return to preoperative body temperature (p = 0.041) and respiratory rate (p = 0.045) on day 7. With respect to pulmonary parameters, there was no significant difference in blood pH, pCO2, or PaCO2 between the transoral and transthoracic groups. All animals survived without complications 14 days after surgery.

This study demonstrated that the transoral approach was comparable to conventional thoracoscopic surgery for lung biopsy and pericardial window creation in terms of safety and efficacy.

Natural orifice transluminal endoscopy has been developed for abdominal surgical procedures. The aim of this study was to compare the surgical outcome between a novel transoral approach and a standard transthoracic approach for the thoracic cavity in a canine model.

Twenty-eight dogs were assigned to transoral (n = 14) or standard thoracoscopy (n = 14). Each group underwent thoracic exploration, pre-determined surgical lung biopsy, and pericardial window creation. Blood draws were obtained before surgery and at postoperative days 1, 3, 7, and 14. Operative time, complications, laboratory parameters, hemodynamic parameters, and inflammatory parameters were compared between the two procedures. The animals were monitored for two weeks and necropsy were performed for surgical outcome evaluation.

The thoracic procedures were successfully performed in all of the dogs, with the exception of one animal in the transoral group. There were no serious acute or delayed complications related to surgery. There was no difference between the two surgical groups for each of the hemodynamic parameters that were evaluated. Regarding the immunological impact of the surgeries, transoral thoracoscopy was associated with significant elevations in interleukin 6 and c-reactive protein levels on postoperative days 1 and 3, respectively, when compared with the standard thoracoscopy. All dogs recovered well, without signs of mediastinitis or thoracic infection. Necropsy revealed absence of infection, no injury to vital organs, and confirmed the success of the novel procedure.

This study suggests that both techniques were comparable with respect to procedure success rate, hemodynamic impact, and inflammatory changes. Furthermore, there was no difference in the incidence of postoperative discomfort between groups.

Natural orifice transluminal endoscopic surgery (NOTES) mediastinoscopy (MED) through the esophagus has proved to be feasible in the animal model. However, injury of the adjacent pleura and pneumothorax has been reported as a frequent adverse event when using a blind access.

To assess the utility and safety of a CT-based image registration system (IRS) for navigation in the mediastinum.

Prospective, randomized, controlled trial in 30 Yorkshire pigs. Thirty-minute MEDs were performed: 15 MEDs were performed with IRS guidance (MED-IRS), and 15 MEDs were performed with a blind access.

Animal research laboratory.

In both groups, the mediastinum was accessed through a 10-cm submucosal tunnel in the esophageal wall. Timed exploration was performed with identification of 8 mediastinal structures.

Technical feasibility, adverse events, and the number of mediastinal structures identified.

Thirty animals weighing 31.5 ± 3.5 kg were included in this study. MED was not possible in 2 animals in the "MED with blind access" group but was possible in all MEDs performed with IRS. The mean number of identified organs was slightly higher in "with IRS-MED" (6.13 ± 1.3) than with MED with blind access (4.7 ± 2.3; P = .066). Moreover, the right atrium and vena cava were identified in more cases with IRS-MED than in MED with blind access (13 vs 3 and 15 vs 11, P = .000 and P = .03, respectively). There were 3 (23%) adverse events with IRS-MED and 4 (27%) with "MED with blind access" (P = not significant), with pneumothorax being the most frequent (2 and 3, respectively).

Nonsurvival animal study.

This study demonstrates that the IRS system appears feasible in natural orifice transluminal endoscopic surgery MED and suggests that IRS guidance might be useful for selected procedures.

Despite the increasing awareness of natural orifice translumenal endoscopic surgery (NOTES), there remain obstacles to its wider implementation. We aim to examine the current evidence for the effects of variable uncontrolled insufflation pressures using either air or carbon dioxide in NOTES, as well the effects of NOTES procedures themselves, on physiological parameters.

We undertook a systematic review of all publications relating to the effects of NOTES on physiology, in particular compared with laparoscopy.

Eleven reports were identified comprising comparative trials involving a total of 237 pigs. With one exception, no difference was found between the effect of NOTES and laparoscopic surgery on cardiopulmonary parameters. No difference was found also for the effect on inflammatory mediators such as interleukin-6. Two studies also assessed the effects choice of insufflation gas, with no change in inflammatory markers. Two further studies assessing the effects of variable pneumoperitoneal pressures found negative cardiorespiratory effects with higher pressures.

Existing evidence is limited to small-sample animal trials but appears to show noninferiority for NOTES compared with laparoscopy. The development of a pressure regulation device for NOTES must be considered.

Transvaginal natural orifice transluminal endoscopic surgery (NOTES) with pneumoperitoneum has been used in cholecystectomies, appendectomies, and nephrectomies, but transvaginal NOTES using a single port in gynecologic procedures has not been described despite gynecologist familiarity with the vaginal approach. We performed transvaginal single-port NOTES in 10 women with benign uterine adnexal disease: oophorectomy in 3 patients, salpingostomy and salpingectomy in 2 each, and ovarian cystectomy, paratubal cystectomy, and ovarian wedge resection in 1 each. The patients were discharged at 1 or 2 days postoperatively, and were satisfied, with minimal pain, no abdominal scar, and no complications at 2-month follow-up. We conclude that transvaginal single-port NOTES to treat benign uterine adnexal disease is a feasible and attractive option.

An ideal wound closure device would repair the wound with minimal complexity. In this report, we describe a simple wound closure method using BioGlue sealant.

Eleven canines underwent transtracheal pericardial window creation under endoscopic guidance for natural orifice transluminal endoscopic surgery (NOTES). The tracheal wound was closed using BioGlue sealant. The integrity of the wound was assessed by determining the amount of air leaking under mechanical ventilation.

Transtracheal thoracic exploration and pericardial window creation was successful for all of the canines, and adequate wound closure was achieved in 10 of the canines. There was 1 case of NOTES-related death arising from misplacement of the endotracheal tube in the left lower lobar bronchus. This caused a collapse of the left upper lobe and ventilatory failure. Minor lung injuries occurred in 3 canines and minor mediastinal bleeding was encountered in 1 canine during the creation of the access site.

BioGlue sealant was found to be effective in sealing the tracheal wound in all but 1 of the canines. This study demonstrates that the use of the sealant is a simple and efficient means of endoscopically closing the tracheal access site in NOTES.

Animal experimentation is necessary to characterize human diseases and design adequate therapeutic interventions. In renal transplantation research, the limited number of in vitro models involves a crucial role for in vivo models and particularly for the porcine model. Pig and human kidneys are anatomically similar (characterized by multilobular structure in contrast to rodent and dog kidneys unilobular). The human proximity of porcine physiology and immune systems provides a basic knowledge of graft recovery and inflammatory physiopathology through in vivo studies. In addition, pig large body size allows surgical procedures similar to humans, repeated collections of peripheral blood or renal biopsies making pigs ideal for medical training and for the assessment of preclinical technologies. However, its size is also its main drawback implying expensive housing. Nevertheless, pig models are relevant alternatives to primate models, offering promising perspectives with developments of transgenic modulation and marginal donor models facilitating data extrapolation to human conditions.

Natural orifice transluminal endoscopic surgery (NOTES) requires fast and steady CO₂ insufflation into the intraluminal and intra-abdominal spaces through a flexible endoscope. However, an optimal endoscopic insufflation system has yet to be determined.

To verify the performances of 2 currently available CO₂ insufflators in an experimental NOTES setting: (1) an automatic pressure-regulated surgical insufflator (UHI-3) and (2) a manual endoscopic insufflator (UCR).

An inanimate bench study followed by an acute animal experiment.

Osaka University and Olympus Research and Development Department.

The UHI-3 or UCR was connected to an endoscope of differing length and diameter via an insufflating line of differing length and diameter. The flow rates at the tip of the endoscope (bench test), the time to establish pneumoperitoneum, and the time to re-establish pneumoperitoneum after forceful suction (porcine model) were obtained.

The UHI-3 failed to feed CO₂ through an insufflating channel but fed CO₂ via a working channel but required a large channel (>3 mm) and a wide insufflating line (>7 mm) to accomplish an acceptable flow rate. UCR fed CO₂ through the insufflating channel; however, the time taken to establish pneumoperitoneum and the time taken to re-establish pneumoperitoneum after forceful suction were longer compared with the time taken for UHI-3 insufflation via the working channel or laparoscopic cannula.

Bench/animal study with small sample numbers; no human trial.

The currently available CO₂ insufflators are not optimal for NOTES. Modification of an endoscopic insufflation system and/or development of a dedicated overtube with an insufflating function are therefore essential.