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1
https://t.me/med1917
Development of
the NOTES Concept
1
https://t.me/med1917
History of NOTES
Xavier Dray
1
APHP H ôpital Lariboisi ère & Universit é Paris 7, Paris, France
2
The Johns Hopkins Hospital, Baltimore, MD, USA
Natural orifi ce translumenal endoscopic surgery (NOTES) is
an endoscopic technique whereby surgical interventions can
be performed with a fl exible endoscope passed through a
natural orifi ce (mouth, vulva, urethra, anus) then through
a translumenal opening of the stomach, vagina, bladder, or
colon [1]. NOTES has the potential to provide no scarring,
reduced pain, and faster patient recovery compared to open
and laparoscopic surgical procedures [1]. We present herein
the landmarks in the history of NOTES, from the early stages
of endoscopy and laparoscopy to its current development.
1,2
& Anthony N. Kalloo
Prehistory of NOTES (from ancient times to
the late twentieth century)
It is diffi cult to date when people started to have a look into
human bodies, and even harder to credit one individual
with the invention of endoscopy. The earliest descriptions
of endoscopy are by Hippocrates (460 –375
described a rectal speculum. A three -bladed vaginal speculum was found in the ruins of Pompeii, demonstrating that
Roman medicine also involved primitive endoscopic
tools. At this time, nothing but ambient light was used, and
only rigid instruments were available. Major technological
developments leading to modern endoscopy and to modern
laparoscopy were born in the nineteenth and twentieth centuries [2].
BC), who
A brief history of endoscopy [3]
The fi rst issue faced by the pioneers of endoscopy was the
illumination problem. The fi rst gastroscopy was reported by
Kussmaul in 1868 [4]. Joseph Swan and Thomas Edison
invented the incandescent electric light bulb in 1878, but
this technology was incorporated into endoscopes only at
the beginning of the twentieth century [3].
2
The second and more challenging problem was fl exibility.
Articulated lenses and prisms were proposed by Hoffmann
in 1911 [5] and improved in 1932 by Wolf and Schindler,
who developed a semi -fl exible gastroscope [6]. However,
the light source consisted of a distal light bulb that provided
poor illumination and produced color distortion. In 1930,
Lamm showed that bundles of glass fi bers could be used as
a conduit for a light source, and that this bundle could be
bent with no effects on light transmission [7]. “Coherent”
bundles, ordered in such a way that the position of a fi ber
at one end mirrors its position at the other end, provided a
real image of internal organs [8]. An external light source
transmitted through fl exible and coherent fi ber bundles
could therefore illuminate internal organs.
Flexibility and illumination were combined by Harold
Hopkins in 1954: the fl exible fi ber imaging device he
invented was made of a tube of glass with thin lenses of air
[9]. In 1958, Larry Curtiss and Basil Hirschowitz improved
this system by using a highly transparent optical quality glass
to give birth to a fl exible fi beroptic endoscope [10].
In the late 1970s, the charge -coupled device (CCD) was
incorporated into an endoscope [11]. This development
heralded the modern era of endoscopy. The CCD allowed
the display of endoscopic images on television screens and
the connection of endoscopes and computers. From this
major shift started a two -decade period described by Sivak
as “the golden era of gastrointestinal endoscopy ” [3]. Major
achievements, which have since become routine procedures, were reported: endoscopic retrograde pancreatography (1968), colonoscopic polypectomy (1969), endoscopic
retrograde cholangiography (1970), endoscopic sphincterotomy with bile duct stone removal (1974), percutaneous
endoscopic gastrostomy (1980), endoscopic injection sclerotherapy (1980), endoscopic ultrasonography (1980), electronic CCD endoscope (1983), endoscopic control of upper
Natural Orifi ce Translumenal Endoscopic Surgery (NOTES): Textbook and Video Atlas, First Edition. Edited by Anthony N. Kalloo, Jacques Marescaux,
Ricardo Zorron.
© 2012 John Wiley & Sons, Ltd. Published 2012 by John Wiley & Sons, Ltd.
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SECTION 1 Development of the NOTES Concept
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gastrointestinal bleeding (1985), and endoscopic variceal
ligation (1990) [3]. Modern endoscopy was born.
A brief history of minimally invasive surgery
Georg Kelling (Dresden, Saxony) reported on the fi rst laparoscopic procedure in animals in 1902. Hans Christian
Jacobaeus (Sweden) performed the fi rst laparoscopic operation in humans in 1910. Many refi nements were brought to
the technique over decades. However, diagnosis and simple
gynecologic procedures were the main applications [2]. A
landmark in this early period of laparoscopy is the fi rst diagnostic laparoscopy by Palmer in the 1950s [12]. In the 1960s
gynecologists took up interventional laparoscopy. The fi rst
CO
hysteroscopy was reported by Frangenheim and Semm
2
in the mid -1970s [2]. Tarasconi (Ob -Gyn, Passo Fundo,
Brazil) reported on the fi rst laparoscopic organ resection
(salpingectomy) in 1976, since published in 1981 [13]. Kurt
Semm (Kiel, Germany) performed the fi rst laparoscopic appendectomy in 1981. Although he is now considered as one of the fathers of modern laparoscopy, he fi rst
met great skepticism and even scorn [14]. His suspension
from medical practice was debated in the German Gynecological Society. The paper that he submitted on “endoscopic
appendectomy” to the American Journal of Obstetrics and Gyne-
cology was initially deemed unethical and was rejected.
Semm persevered, introduced thermocoagulation, and
developed many standard laparoscopic gynecologic procedures, including ovarian cyst enucleation, myomectomy,
treatment of ectopic pregnancy, and laparoscopic -assisted
vaginal hysterectomy. He published hundreds of papers on
laparoscopy, established a company of laparoscopic instruments, and built the widely used pelvi -trainer [14]. By the
end of the 1980s, laparoscopy was widely accepted in gynecology, but few general surgeons had included laparoscopy
in their practice. The fi rst lap -cholecystectomy was made by
Erich Muhe (Erlangen, Germany) in 1986. Muhe met a lot
of misunderstanding from his colleagues at this time, and
even faced a lawsuit for “improper surgical action ” [15].
The use of the computer chip TV camera in 1986 led to
the era of modern laparoscopy: not only was a view of the
operative fi eld magnifi ed onto a monitor, but also the
surgeon could stand upright, and both his/her hands were
free. Complex laparoscopic procedures were then developed. Philippe Mouret (Lyon, France) performed the
fi rst video-assistedlaparoscopic cholecystectomy in 1987.
Mouret mentored Dubois (Paris, France), Perissat (Bordeaux, France), and other collaborators. The so -called
“French connection ” made the laparoscopic technique more
and more popular [16]. The fi rst US laparoscopic cholecystectomy was performed in 1988. In the early 1990s, laparoscopic cholecystectomy was an accepted routine procedure.
A dramatic explosion of laparoscopic applications occurred
in the 1990s. Among others, landmarks in the history of
laparoscopy are the fi rst descriptions of truncal vagotomy
[17], nephrectomy [18], Billroth II gastrectomy [19], and
splenectomy [20]. Similar developments have been achieved
in thoracic surgery in the past 30 years. Minimally invasive
surgery is now seen as one of the greatest achievements in
the recent history of medicine.
On the verge of NOTES (1980 –2000)
Translumenal endoscopic approaches
From the 1980s to the 2000s, numerous translumenal endoscopic procedures emerged. Some of them are now part of
the routine practice of gastrointestinal endoscopy. Various
endoscopic techniques consist of the creation of an artifi cial
external opening into the digestive tract for nutritional
support or gastrointestinal decompression. Percutaneous
endoscopic gastrostomy (PEG) creation without laparoscopic
assistance was fi rst reported in 1980 by Gauderer et al. [21],
then followed by variations such as percutaneous endoscopic jejunostomy and colostomy [22,23]. Endoscopic
ultrasound (EUS) arose in 1980 [24]. Diagnostic EUS procedures were fi rst based on imaging and Doppler only. Under
EUS guidance, the fi ne needle aspiration (FNA) technique
was developed to allow the sampling of lesions through the
digestive wall [25]. EUS -FNA is now commonly used to
target lesions in the mediastinum, in the biliary and pancreatic area, and in the mesorectum. Further refi nement of the
EUS technique has led to the ability to pass instruments
(guidewires, fi ducials, coils, radioactive seeds, pharmacological agents) using fi ne needles, leading to the concept of
interventional EUS. Biliary, pancreatic, and vascular therapeutic EUS techniques are currently under evaluation [26].
Translumenal per -oral endoscopic access to the retroperitoneum is another gastrointestinal technique preceding the
birth of NOTES. It was fi rst described by Hans Seifert (Oldenburg, Germany) in 2000 [27]. After endoscopic transmural drainage of peripancreatic fl uid collections is performed
with EUS -FNA and wire -guided stent placement, the same
transgastric access is expanded with balloon dilatation. The
endoscope is advanced through the gastrointestinal wall into
the retroperitoneum. Endoscopic removal of infected pancreatic necroses can be achieved under direct visual control.
In a multicenter open study, initial clinical success was
obtained in 80% of 93 patients, with a 26% complication
and a 7.5% mortality rate at 30 days [28]. Similar results
were found in a US multicenter study that included 104
patients [29]. Although not compared to surgery in randomized controlled studies, this endoscopic technique has
become a valid therapeutic option. The concept of endoscopic debridement of necrosis was expanded to other conditions than pancreatitis and is now performed in expert
centers to treat complications of postoperative leakage and
fi stula [30]. Although PEG, FNA -EUS, and endoscopic drainage of necrosis are defi nitely translumenal endoscopic pro-
4
CHAPTER 1 History of NOTES
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cedures conducted through natural orifi ces they are not
considered as true NOTES procedures as the endoscope is
not advanced in the free peritoneal or thoracic cavity.
Transvaginal laparoscopy
Transvaginal hydrolaparoscopy is a surgical technique that
arose in the 1990s with the main purpose of diagnosing and
treating infertility in women. The technique used a modifi ed
rigid and reusable laparoscope. The so -called “fertiloscopy”
procedure combines a hydrolaparoscopy advanced through
the vagina and the pouch of Douglas together with hysteroscopy and salpingoscopy with dye. A pioneer in this fi eld
is Antoine Watrelot (Lyon, France). After he developed the
technique, he demonstrated that fertiloscopy is useful in the
diagnosis of tubo -peritoneal abnormalities (a major causes
of infertility), enables rational choices in the therapeutic
strategy of infertility, improves pregnancy rates, and allows
reductions in costs [31]. The technique does not involve a
fl exible instrument and is not dedicated to the exploration
of the entire peritoneal cavity. However, it is seen as a close
step on the way to NOTES.
The birth of NOTES (2000)
Flexible endoscopic procedures have become more and
more invasive over recent decades. At the end of the twentieth century, frontiers in endoscopy were broken in a step wise fashion. Diagnosis endoscopy is now possible all along
the digestive tract (including the small bowel) and even in
the duct of its main accessory glands (cholangioscopy, pancreatoscopy) [32]. Imaging and sampling of organs beyond
the digestive tract have been made possible by EUS -FNA.
The most recent step was the possibility of voluntarily
causing a breach in the integrity of the digestive wall to
access and treat necrosis in the retroperitoneum [33].
Conversely, surgery is getting less and less invasive. Dr
Hunter’s quote in 1762 – “Surgery, gaining much from the
general advance of knowledge, will be rendered both knifeless and bloodless ” – was much ahead of his time. At the
end of the twentieth century, laparoscopy has been demonstrated safe and cost -effi cient, in a wide range of applications
in abdominal, pelvic, and thoracic surgery. It has been fully
accepted by medical and surgical communities. Minimally
invasive surgery has therefore gained patients ’ satisfaction
over the years and is now a standard of care for many indications. Some of its latest developments are the possibility
to access and to treat through natural orifi ces (mostly
through the vagina) and/or through a unique and small
parietal incision (as proposed in single -incision laparoscopic
surgery, SILS).
NOTES is born from the confl uence of these two trends
(Figure 1.1). Anthony Kalloo and the team (Figure 1.2) from
the Johns Hopkins Hospital (Baltimore, USA) reported on
the fi rst NOTES procedure (transgastric peritoneoscopy) in
a survival porcine model during the 2000 edition of the
Digestive Disease Week (DDW) (see Video 1.1). In this initial
approach (fi nally published in 2004) [34], access to the
peritoneal cavity was gained with a fl exible videogastroscope through the mouth and after needle -knife puncture
Figure 1.1 Synoptic view of the confl uence
of interventional endoscopy and minimally
invasive surgery over time, leading to the birth
of NOTES.
Invasiveness
of intervention
Open surgery
Laparoscopy
NOTES
Interventional
Diagnostic endoscopy
1900 1950 1980 2005 Present
endoscopy
Time
5
SECTION 1 Development of the NOTES Concept
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Figure 1.2 Sergey V. Kantsevoy, Sanjay B. Jagannath, Anthony N.
Kalloo, and Hu Bing.
Figure 1.4 NOSCAR group, July 2005.
nels, increased push force, wider freedom of movement, and
variable rigidity [36]. Approximating and sewing instruments were developed. Among others, the group of Paul
Swain (London, United Kingdom) was extremely active on
this topic [37]. Along with these advances in the design of
instruments, early procedures were refi ned, with animal
experiments on organ removal and anastomosis, leading to
the fi rst descriptions of NOTES gastrojejunostomy, fallopian
tube ligation, hysterectomy, and cholecystectomy [38–41].
Figure 1.3 Dr G.V. Rao and Dr D.N. Reddy.
and balloon dilatation of the anterior wall of the stomach.
Peritoneoscopy and liver biopsies were performed. Hemoclips were used to close the gastrotomy. Two years later, Rao
and Reddy (Hyderabad, India) reported on the fi rst human
case (transgastric NOTES appendectomy) in a DDW video
session (Figure 1.3) [35].
NOTES launching (2000 –2004)
After its initial description, a few research groups showed
interest in NOTES. At this early stage, much work was done
out of the public view. Developmental studies aimed to
make fl exible endoscopes and ancillary instruments suitable
and safe for translumenal access, and surgical procedures
were being developed. Endoscope and overtube prototypes
were conceived and designed with larger accessory chan-
NOTES booming (2005 –2008)
NOTES societies
In July 2005, US leaders in the fi elds of both laparoscopy
and gastrointestinal endoscopy came together for a summit
meeting in New York City. These experts built up the Natural
Orifi ce Surgery Consortium for Assessment and Research
(NOSCAR) group, a joint initiative supported by the American Society for Gastrointestinal Endoscopy (ASGE) and the
Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) (Figure 1.4). From this meeting, the NOSCAR
group published a fi rst White Paper in 2006 that aimed to
guide research on NOTES [42]. The key message of the
group was that developmental work and animal study were
required before safe clinical evaluation could be attempted
(Table 1.1). The group successfully called for the involvement of the industries of both endoscopy and surgery. Their
fi rst annual meeting under the name of NOSCAR was held
in Boston in 2006. The fi rst NOSCAR research grants were
awarded in 2006, since then followed by yearly awards.
Other international groups with similar goals and means
followed this move throughout the world. In 2007, the fi rst
joint meeting of the European Association for Endoscopic
Surgery (EAES) and the European Society of Gastrointesti-
6
Table 1.1 Potential barriers to the development of NOTES, as listed
https://t.me/med1917
by the NOSCAR consortium.
Access to peritoneal cavity
Gastric (intestinal) closure
Prevention of infection
Development of suturing and anastomotic devices
Spatial orientation
Development of a multitasking platform to accomplish procedures
Management of intraperitoneal complications
Physiologic untoward events
Compression syndromes
Training
CHAPTER 1 History of NOTES
(Reproduced from Rattner and Kalloo [42], with kind permission from
Springer Science + Business Media.)
nal Endoscopy (ESGE) on Natural Orifi ce Translumenal
Endoscopic Surgery (EuroNOTES) was held in Sweden.
NOTES early animal experiments
From the initial reports of per -oral transgastric fl exible
peritoneoscopy, it was expected for NOTES to offer a
wide array of diagnostic and therapeutic procedures. Under
the guidance of NOTES societies, and with their funding
in many cases, numerous procedures and tools were developed in this period in laboratories. Most procedures were
attempted in pigs of various breeds, and more rarely in
dogs or in human cadavers. The following selection of
procedures is not exhaustive, but it gives an idea of the
fl ourishing research activity that emerged from the initial
description of NOTES. Early transgastric experimental procedures included creation of anastomosis [41,43,44], gynecologic surgery [39,41,45,46], and cholecystectomy [47].
Transgastric NOTES was combined with other innovative
techniques such as EUS [48], confocal endomicroscopy [49],
closure devices [47,50–52], and robots [53]. Other access
routes to the peritoneal cavity were evaluated, as illustrated
by reports on transcolonic peritoneoscopy [54], hernia
repair [55], and cholecystectomy [56], on transvesical peritoneoscopy [57] and thoracoscopy [58], and on transesophageal procedures [59].
NOTES in human medicine (2009 –2011)
Transgastric NOTES waning
Although most of the above -mentioned transgastric experiments in animals met with technical success, most procedures were tedious and did not allow immediate translation
for clinical practice. Since the initial report of transgastric
NOTES appendectomy by Rao and Reddy in 2002 [35], only
Figure 1.5 Zorron team.
a few clinical reports on transgastric NOTES have been published. In most cases, laparoscopic assistance was deemed
necessary by the operators and by ethics committees.
Laparoscopy-assisted transgastric diagnostic fl exible peritoneoscopy has been performed at the time of oncological [60]
or bariatric [61] surgery in short series. Only a few cases of
pure transgastric NOTES procedures have been reported in
human patients [62].
Transvaginal NOTES breakthrough
Based on the strong experience of fertiloscopy preceding
the birth of NOTES, the transvaginal route met most of the
expectations of surgeons for a safe and reliable access to
the peritoneal cavity. Although it excludes male patients to
benefi t from the technique, most surgeons involved in the
development of NOTES proposed to move forward by starting clinical series with the transvaginal approach. Cholecystectomy was felt to be a standard surgical procedure that
could be easily translated from the laparoscopic to the
NOTES approach. The fi rst series were lap -assisted (hybrid
NOTES). Audacious surgeons from South America took the
lead. In 2007, Ricardo Zorron (Rio de Janeiro, Brazil) published the fi rst report of transvaginal hybrid NOTES cholecystectomy (Figure 1.5) [63]. As the technique was refi ned,
rigid laparoscopic instruments and ports were progressively
reduced in terms of numbers and size. Jacques Marescaux
(Figure 1.6) from Strasbourg, France, soon followed by
Mark Bessler (Figure 1.7) from New York, USA, reported on
the fi rst NOTES cholecystectomy without any laparoscopic
assistance (also known as “pure NOTES ”). These major
achievements received a large echo in the media, favoring
further development and evaluation of the technique. The
fi rst series of transvaginal hybrid NOTES cholecystectomy
were published in 2008 [64–66]. Data from the German
NOTES registry have since confi rmed that transvaginal
7
SECTION 1 Development of the NOTES Concept
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Figure 1.6 Jacques Marescaux.
hybrid NOTES cholecystectomy was a safe alternative to the
laparoscopic approach. Although not compared to laparoscopy, NOTES was favorably evaluated in 551 patients
(including 470 cholecystectomies), with a complication rate
of 3.1% and a conversion rate to laparoscopy or to open
surgery in 4.9% [67]. The NOSCAR consortium has started
a prospective multicenter trial comparing NOTES cholecystectomy with conventional laparoscopic cholecystectomy in
the USA.
NOTES offspring
The development of NOTES has served (and is still serving)
other concepts in the development of interventional endoscopy and minimally invasive surgery.
Collateral development in interventional
endoscopy
The development of innovative devices for access and closure
during NOTES procedures has offered new possibilities to
therapeutic endoscopists. Submucosal endoscopy is a direct
result of targeting NOTES procedures in an attempt to
develop safe access and quick closure. An early proposal to
secure access to the mediastinum and to the peritoneal
cavity was to create endoscopically a tunnel in the submucosal layer of the digestive wall. The technique was named
Figure 1.7 Marc Bessler.
submucosal endoscopy with mucosal fl ap (SEMF). By separating the mucosal access to the submucosa from the muscular breach giving access to surrounding organs, and by
using a mucosal fl ap to cover the tunnel, the operators
aimed to decrease the risk of contamination [59,68–70].
Since then, this approach has been developed and evaluated
for the endoscopic treatment of achalasia, called per -oral
endoscopic myotomy (POEM) [71,72]. The research on
NOTES has also provided new tools for endoscopic full thickness resection of tumors [73,74] and for the treatment
of endoscopic perforations. Bariatric endoscopy also greatly
benefi ts from the research on endoscopic sutures and anastomosis during NOTES [75,76].
Collateral development in minimally invasive
surgery
Transumbilical surgery is another example. The umbilicus is
not strictly considered as a natural orifi ce and it is therefore
not included in the narrow spectrum of NOTES. However,
transumbilical surgery clearly benefi ts from the advances of
NOTES (and vice versa). The concepts of natural orifi ce
transumbilical surgery (NOTUS), transumbilical endoscopic
surgery (TUES), and transumbilical laparoscopic assisted
(TULA) have arisen from this idea. They are now endlessly
combined to other concepts, including laparo -endoscopic
single-site (LESS) and single -incision laparoscopic surgery
(SILS), and fl exible endoscopy (fl exible SILS), thus expo-
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CHAPTER 1 History of NOTES
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nentially increasing the fi eld of minimally invasive surgery.
Transanal endoscopic microsurgery (TEM) is also an expanding fi eld of surgery with a close relationship to the technical
advances of NOTES [77].
Conclusion
Initially described by gastroenterologists by a pure per -oral
transgastric route in the pig model, NOTES is now mainly
performed by surgeons, through the transvaginal route, in
human patients. NOTES is a result of the natural evolution
of endoscopy and laparoscopic surgery in the quest to deliver
less invasive patient care. It is currently in its infancy but
will grow to be part of our armamentarium of approaches
to patient care.
Chapter video clip
Video 1.1 First NOTES peritoneoscopy.
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CHAPTER 1 History of NOTES
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